{ "classification_aggregates": [ { "aggregate": true, "id": "__aggregate__", "label": "All granted", "type": "grant" } ], "papers": [ { "abstract": "Cellular senescence is accompanied by complex changes in nuclear mechanics. Here, integrated Raman, Brillouin, and refractive index imaging quantitatively revealed that senescent nuclei exhibit an increased high-frequency viscoelastic response, despite the increase in nuclear water content and volume and the decrease in biomolecular density. This discrepancy indicates that the nuclear mechanical alteration in senescent cells is not simply due to molecular condensation, as discussed in the context of chromatin reorganization.", "classifications": [ { "id": "Nakabayashi", "label": "Group Nakabayashi", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Lisa", "last_name": "Kageyama", "name": null }, { "creator_type": "author", "first_name": "Ryota", "last_name": "Dobashi", "name": null }, { "creator_type": "author", "first_name": "Masato", "last_name": "Machida", "name": null }, { "creator_type": "author", "first_name": "Kazunori", "last_name": "Ban", "name": null }, { "creator_type": "author", "first_name": "Shinji", "last_name": "Kajimoto", "name": null }, { "creator_type": "author", "first_name": "Takakazu", "last_name": "Nakabayashi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1039/d6cc03641d" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "42638522" } }, "mesh": [], "publication": { "conference_name": null, "date": "2026 Aug 25", "date_precision": "day", "issue": "", "normalized_date": "2026-08-25", "pages": "", "proceedings_title": null, "publisher": "", "title": "Chemical communications (Cambridge, England)", "volume": "", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "Multimodal label-free imaging reveals increased nuclear hydration and apparent stiffening during cellular senescence.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "An aberrant wound-healing response to chronic liver injury results in excessive accumulation of extracellular matrix proteins, including collagen, leading to liver fibrosis, a process in which hepatocytes and hepatic stellate cells (HSCs) play key roles. In this study, we present HepG2 and LX-2 cocultured spheroids as a three-dimensional in vitro model of liver fibrosis and highlight the potential of hyperspectral Raman imaging as a label-free analytical approach for assessing fibrosis-associated responses. HepG2 cells and LX-2 cells served as hepatocytes and HSCs, respectively, within the coculture spheroids. Hyperspectral Raman imaging allowed for the acquisition of fingerprint spectra from individual cells, revealing distinct cytochrome-related band patterns that facilitated cell-type segmentation without labeling. To induce fibrosis, spheroids were treated with fibrosis activation factors: free fatty acids (FFAs) and transforming growth factor-β (TGF-β). FFA administration induced steatotic features in the coculture spheroids, as demonstrated by a direct correlation between the increasing lipid band intensity in the Raman spectra and FFA concentrations. Concurrently, a reduced cytochrome-related band intensity was observed in these spheroids. Furthermore, LX-2 spheroids but not HepG2 spheroids exhibited signs of fibrosis after TGF-β activation. Raman analysis revealed that the amide I and III bands reflected extracellular matrix, especially collagen accumulation, applied as fibrosis markers. Notably, in the 2:1 coculture spheroids, we observed enhanced fibrosis-related bands in the LX-2-enriched regions. The consistency between Raman imaging results and immunofluorescent images underscores the potential of hyperspectral Raman imaging as a sensitive and noninvasive method for assessing liver fibrosis.", "classifications": [ { "id": "Fujita", "label": "Group Fujita", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Gunganist", "last_name": "Kongklad", "name": null }, { "creator_type": "author", "first_name": "Menglu", "last_name": "Li", "name": null }, { "creator_type": "author", "first_name": "Tomoko", "last_name": "Yamashita", "name": null }, { "creator_type": "author", "first_name": "Tomoaki", "last_name": "Okumura", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Fujita", "name": null }, { "creator_type": "author", "first_name": "Katsumasa", "last_name": "Fujita", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/cbmi.5c00243" }, "pmcid": { "normalized": "PMC13508106" }, "pmid": { "normalized": "42656890" } }, "mesh": [], "publication": { "conference_name": null, "date": "2026 Aug 24", "date_precision": "day", "issue": "8", "normalized_date": "2026-08-24", "pages": "1695-1705", "proceedings_title": null, "publisher": "", "title": "Chemical & biomedical imaging", "volume": "4", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "Label-Free Hyperspectral Raman Imaging and Analysis of a 3D Spheroid Model for Liver Fibrosis Study.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Pancreatic ductal adenocarcinoma (PDAC) is the cancer with poorest prognosis, with metabolic reprogramming reported. We investigated metabolic alterations in mice with PDAC using capillary electrophoresis-mass spectrometry (CE-MS) and mass spectrometry imaging (MSI). o-Acetylcarnitine, a metabolite of carnitine, and acetyl-CoA increased during cancer progression in a PDAC mouse model by CE-MS, while MSI revealed that o-acetylcarnitine was mainly localized in PDAC cells. Also, immunohistochemistry showed overexpression of gamma-butyrobetaine 2-oxoglutarate dioxygenase 1 (BBOX1), which synthesizes carnitine from gamma-butyrobetaine, mainly in PDAC cells. Meldonium, an inhibitor of BBOX1, inhibited PDAC proliferation and cytokine secretion, thereby prolonging the survival of PDAC-bearing mice, accompanied by improved skeletal muscle atrophy. In patients undergoing PDAC resection, BBOX1 expression was determined as an independent poor prognostic factor for overall survival. Therefore, these results suggest that blocking L-carnitine synthesis would improve the prognosis of patients with PDAC.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Makoto", "last_name": "Sano", "name": null }, { "creator_type": "author", "first_name": "Hideaki", "last_name": "Ijichi", "name": null }, { "creator_type": "author", "first_name": "Sho", "last_name": "Tabata", "name": null }, { "creator_type": "author", "first_name": "Akiyoshi", "last_name": "Hirayama", "name": null }, { "creator_type": "author", "first_name": "Shuichi", "last_name": "Shimma", "name": null }, { "creator_type": "author", "first_name": "Yohei", "last_name": "Masugi", "name": null }, { "creator_type": "author", "first_name": "Yoshimi", "last_name": "Ichimaru", "name": null }, { "creator_type": "author", "first_name": "Jinsuk", "last_name": "Kim", "name": null }, { "creator_type": "author", "first_name": "Gen", "last_name": "Kimura", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Miyabayashi", "name": null }, { "creator_type": "author", "first_name": "Ryota", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Hiroto", "last_name": "Hatakeyama", "name": null }, { "creator_type": "author", "first_name": "Takahiro", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Masamune", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Mitsuhiro", "last_name": "Fujishiro", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.isci.2026.117071" }, "pmcid": { "normalized": "PMC13475670" }, "pmid": { "normalized": "42602712" } }, "mesh": [], "publication": { "conference_name": null, "date": "2026 Aug 21", "date_precision": "day", "issue": "8", "normalized_date": "2026-08-21", "pages": "117071", "proceedings_title": null, "publisher": "", "title": "iScience", "volume": "29", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "Blocking L-carnitine synthesis by meldonium prolongs the survival in mice with pancreatic cancer.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Feeding behavior, which is crucial for all mammals, is regulated by a delicate equilibrium between the orexigenic and anorexigenic activities of hypothalamic neurons. This exquisite control of the neuropeptides that govern the feeding behavior could be a focal point in the pathogenesis of obesity. We reported that inactivation of C-terminal binding protein 2 (CtBP2), a transcriptional corepressor with metabolite-sensing capabilities, contributes to the pathogenesis of obesity in liver tissues and pancreatic beta-cells. Here, we describe a transcriptional system regulated by CtBP2 in the hypothalamus. Our global mapping of CtBP2 binding sites using ChIP-seq combined with functional analyses revealed that CtBP2 functions as a corepressor for orexigenic neuropeptide promoters. In response to the metabolic abnormalities associated with obesity, CtBP2 undergoes allosteric inactivation and dissociates from these promoters, thereby resulting in the derepression of orexigenic neuropeptide expression. Consistently, the loss of CtBP2 in hypothalamic neurons in mice increases the expression of orexigenic neuropeptides, thus leading to increased feeding behavior. These findings highlight how obesity disrupts homeostatic mechanisms that normally maintain body weight within a healthy range.", "classifications": [ { "id": "Miyamoto", "label": "Group Miyamoto", "parent": "Wakamoto", "type": "group" }, { "id": "Wakamoto", "label": "Team Wakamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Wanpei", "last_name": "Chen", "name": null }, { "creator_type": "author", "first_name": "Kenta", "last_name": "Kainoh", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Takaaki", "last_name": "Matsuda", "name": null }, { "creator_type": "author", "first_name": "Daichi", "last_name": "Yamazaki", "name": null }, { "creator_type": "author", "first_name": "Yuto", "last_name": "Kobari", "name": null }, { "creator_type": "author", "first_name": "Ayumi", "last_name": "Nakata", "name": null }, { "creator_type": "author", "first_name": "Nao", "last_name": "Aono-Soma", "name": null }, { "creator_type": "author", "first_name": "Takafumi", "last_name": "Miyamoto", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Murayama", "name": null }, { "creator_type": "author", "first_name": "Yoko", "last_name": "Sugano", "name": null }, { "creator_type": "author", "first_name": "Yoshinori", "last_name": "Osaki", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Iwasaki", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Matsuzaka", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Shimano", "name": null }, { "creator_type": "author", "first_name": "Motohiro", "last_name": "Sekiya", "name": null } ], "identifiers": { "doi": { "normalized": "10.1096/fj.202602322r" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "42522895" } }, "mesh": [ { "descriptor": "Alcohol Oxidoreductases", "descriptor_ui": "D000429", "major_topic": true }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Co-Repressor Proteins", "descriptor_ui": "D056970", "major_topic": false }, { "descriptor": "Feeding Behavior", "descriptor_ui": "D005247", "major_topic": true }, { "descriptor": "Gene Expression Regulation", "descriptor_ui": "D005786", "major_topic": false }, { "descriptor": "Hypothalamus", "descriptor_ui": "D007031", "major_topic": true }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Nerve Tissue Proteins", "descriptor_ui": "D009419", "major_topic": true }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Neuropeptides", "descriptor_ui": "D009479", "major_topic": false }, { "descriptor": "Obesity", "descriptor_ui": "D009765", "major_topic": true }, { "descriptor": "Promoter Regions, Genetic", "descriptor_ui": "D011401", "major_topic": false }, { "descriptor": "Transcription, Genetic", "descriptor_ui": "D014158", "major_topic": true } ], "publication": { "conference_name": null, "date": "2026 Aug 15", "date_precision": "day", "issue": "15", "normalized_date": "2026-08-15", "pages": "e72172", "proceedings_title": null, "publisher": "", "title": "FASEB journal : official publication of the Federation of American Societies for Experimental Biology", "volume": "40", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "Obesity Disrupts CtBP2-Mediated Maintenance of Transcriptional Equilibrium in Hypothalamic Feeding Circuitry.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "INTRODUCTION: Tumor spread through air spaces (STAS) and histologic tumor grade have been reported as adverse prognostic factors in non-small cell lung cancer (NSCLC), yet their impact on the extent of surgical resection remains insufficiently defined. This study aimed to evaluate the prognostic impacts of STAS and tumor grade in stage IA patients (pT1a/bN0) from JCOG0802/WJOG4607L comparing segmentectomy and lobectomy. METHODS: STAS and tumor grading were assessed in 593 tumors by 32 expert pulmonary pathologists across the world. The prognostic impact of STAS in lobectomy (n=294) versus segmentectomy (299) in relation to relapse-free survival (RFS) and overall survival (OS) was evaluated, as well as the association of STAS with histologic grading. RESULTS: STAS was identified in 227 cases (38.3%) and was significantly associated with shorter relapse-free survival (RFS) and overall survival (OS) (RFS HR=2.204; OS HR=1.917; both p<0.001). Multivariable analysis confirmed STAS as an independent adverse factor for RFS (p<0.001) and OS (p=0.009). STAS was associated with higher local recurrence in both lobectomy and segmentectomy approaches (p=0.012 and p=0.002, respectively). STAS independently predicted shorter RFS in both lobectomy and segmentectomy subgroups, but only OS in the lobectomy subgroup. Among invasive non-mucinous adenocarcinomas, histologic grade 3 was strongly associated with STAS (p<0.001) and poor outcomes. Both STAS and grade 3 independently predicted shorter RFS, whereas only grade 3 predicted OS. CONCLUSIONS: These findings reinforce STAS and high-grade adenocarcinoma as clinically significant prognostic factors and support their incorporation into risk stratification for stage IA (pT1a/bN0) NSCLC patients.", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null }, { "creator_type": "author", "first_name": "Mary Beth", "last_name": "Beasley", "name": null }, { "creator_type": "author", "first_name": "Alain", "last_name": "Borczuk", "name": null }, { "creator_type": "author", "first_name": "Sabina", "last_name": "Berezowska", "name": null }, { "creator_type": "author", "first_name": "Lukas", "last_name": "Bubendorf", "name": null }, { "creator_type": "author", "first_name": "Wei-Chin", "last_name": "Chang", "name": null }, { "creator_type": "author", "first_name": "Teh-Ying", "last_name": "Chou", "name": null }, { "creator_type": "author", "first_name": "Wendy A.", "last_name": "Cooper", "name": null }, { "creator_type": "author", "first_name": "Sanja", "last_name": "Dacic", "name": null }, { "creator_type": "author", "first_name": "Yuchen", "last_name": "Han", "name": null }, { "creator_type": "author", "first_name": "Takuo", "last_name": "Hayashi", "name": null }, { "creator_type": "author", "first_name": "Paul", "last_name": "Hofman", "name": null }, { "creator_type": "author", "first_name": "David M.", "last_name": "Hwang", "name": null }, { "creator_type": "author", "first_name": "Deepali", "last_name": "Jain", "name": null }, { "creator_type": "author", "first_name": "Philippe", "last_name": "Joubert", "name": null }, { "creator_type": "author", "first_name": "Keith", "last_name": "Kerr", "name": null }, { "creator_type": "author", "first_name": "Tae-Jung", "last_name": "Kim", "name": null }, { "creator_type": "author", "first_name": "Satsuki", "last_name": "Kishikawa", "name": null }, { "creator_type": "author", "first_name": "John", "last_name": "Le Quesne", "name": null }, { "creator_type": "author", "first_name": "Dongmei", "last_name": "Lin", "name": null }, { "creator_type": "author", "first_name": "Fernando", "last_name": "Lopez-Rios", "name": null }, { "creator_type": "author", "first_name": "Yuko", "last_name": "Minami", "name": null }, { "creator_type": "author", "first_name": "Mari", "last_name": "Mino-Kenudson", "name": null }, { "creator_type": "author", "first_name": "Noriko", "last_name": "Mitome", "name": null }, { "creator_type": "author", "first_name": "Andrew G.", "last_name": "Nicholson", "name": null }, { "creator_type": "author", "first_name": "Mauro", "last_name": "Papotti", "name": null }, { "creator_type": "author", "first_name": "Anja C.", "last_name": "Roden", "name": null }, { "creator_type": "author", "first_name": "Hisashi", "last_name": "Saji", "name": null }, { "creator_type": "author", "first_name": "Anjali", "last_name": "Saqi", "name": null }, { "creator_type": "author", "first_name": "Hyo Sup", "last_name": "Shim", "name": null }, { "creator_type": "author", "first_name": "Fabio Rocha", "last_name": "Fernandes Tavora", "name": null }, { "creator_type": "author", "first_name": "Jan", "last_name": "von der Thusen", "name": null }, { "creator_type": "author", "first_name": "Akihiko", "last_name": "Yoshizawa", "name": null }, { "creator_type": "author", "first_name": "Masashi", "last_name": "Wakabayashi", "name": null }, { "creator_type": "author", "first_name": "Shun-Ichi", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Hisao", "last_name": "Asamura", "name": null }, { "creator_type": "author", "first_name": "Ming-Sound", "last_name": "Tsao", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.jtho.2026.104156" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "42600842" } }, "mesh": [], "publication": { "conference_name": null, "date": "2026 Aug 14", "date_precision": "day", "issue": "", "normalized_date": "2026-08-14", "pages": "104156", "proceedings_title": null, "publisher": "", "title": "Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer", "volume": "", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "Prognostic Significance of Spread Through Airspaces (STAS) in Stage Ia/bN0 Non-small Cell Lung Cancer - An Evaluation in the JCOG0802/WJOG4607L Clinical Trial Patients.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Upon entry into the G1 phase following mitosis, mammalian chromosomal DNA becomes spatially segregated into A and B compartments, which correspond closely to classic euchromatin and heterochromatin, respectively. The functional significance of this spatial segregation, however, has remained unexplored due to the lack of means to manipulate this level of chromosomal organization. Through a genome-wide loss-of-function CRISPR screen, we identify GINS4, a component of the replicative DNA helicase complex, as a factor essential for segregation of A and B compartments during the G1-to-S phase transition. Using GINS4 depletion experiments, we show that proper A/B compartment organization at the time of S-phase entry plays a key role in efficient DNA synthesis. Furthermore, DNA synthesis with attenuated A/B compartments is associated with defects in replication timing regulation. Our findings uncover a previously unrecognized role for GINS4 in regulating nuclear architecture and underscore the biological significance of nuclear compartmentalization in DNA replication control.", "classifications": [ { "id": "Yusa", "label": "Group Yusa", "parent": "Eiraku", "type": "group" }, { "id": "Eiraku", "label": "Team Eiraku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Asami", "last_name": "Oji", "name": null }, { "creator_type": "author", "first_name": "Kosuke", "last_name": "Yusa", "name": null }, { "creator_type": "author", "first_name": "Izumi", "last_name": "Noda", "name": null }, { "creator_type": "author", "first_name": "Takako", "last_name": "Ichinose", "name": null }, { "creator_type": "author", "first_name": "Yoshiko", "last_name": "Kondo", "name": null }, { "creator_type": "author", "first_name": "Ichiro", "last_name": "Hiratani", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41467-026-75264-6" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "42575893" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Nucleus", "descriptor_ui": "D002467", "major_topic": true }, { "descriptor": "Chromosomal Proteins, Non-Histone", "descriptor_ui": "D002868", "major_topic": false }, { "descriptor": "DNA", "descriptor_ui": "D004247", "major_topic": false }, { "descriptor": "DNA Replication", "descriptor_ui": "D004261", "major_topic": true }, { "descriptor": "G1 Phase", "descriptor_ui": "D016193", "major_topic": true }, { "descriptor": "HeLa Cells", "descriptor_ui": "D006367", "major_topic": false }, { "descriptor": "Heterochromatin", "descriptor_ui": "D006570", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mitosis", "descriptor_ui": "D008938", "major_topic": false }, { "descriptor": "S Phase", "descriptor_ui": "D016196", "major_topic": true } ], "publication": { "conference_name": null, "date": "2026 Aug 10", "date_precision": "day", "issue": "1", "normalized_date": "2026-08-10", "pages": "6961", "proceedings_title": null, "publisher": "", "title": "Nature communications", "volume": "17", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "Nuclear compartmentalization at the G1/S transition plays a key role in DNA replication control.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The spatial arrangement of cells is fundamental to the mechanical and functional integrity of three-dimensional (3D) tissues, yet engineering spatially well-controlled tissue architectures remains challenging. Here, we computationally investigated how layered tissue architectures can be designed by modulating tension at cellular interfaces (i.e., free-surface and cell-cell interfaces). We performed simulations using a 3D vertex model and systematically varied interfacial tension magnitudes. The simulations generated a range of layered tissue architectures, including planar monolayers, bilayers, and structurally stratified states. In homogeneous cell populations, increasing interfacial tension drove transitions from monolayer to structurally stratified configurations. In heterogeneous populations, differential interfacial tensions induced out-of-plane cell sorting and the formation of compositionally sorted multilayers. Moreover, a recursive tension design strategy enabled hierarchical organization of multiple cell types into separate layers. Notably, this recursive scheme uses only two tension levels (high vs. low) assigned across interfaces and can, in principle, be extended to specify layered architectures with an arbitrary number of layers. Together, these results identify cell-cell interfacial tension as a tunable mechanical parameter for regulating layered tissue architecture and provide design principles for layered tissue engineering and regenerative medicine.", "classifications": [ { "id": "Okuda", "label": "Group Okuda", "parent": "Imayoshi", "type": "group" }, { "id": "Imayoshi", "label": "Team Imayoshi", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Chayanit", "last_name": "Thiticharoentam", "name": null }, { "creator_type": "author", "first_name": "Shuya", "last_name": "Fukamachi", "name": null }, { "creator_type": "author", "first_name": "Shuhei A.", "last_name": "Horiguchi", "name": null }, { "creator_type": "author", "first_name": "Satoru", "last_name": "Okuda", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.jmbbm.2026.107597" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "42600503" } }, "mesh": [], "publication": { "conference_name": null, "date": "2026 Aug 8", "date_precision": "day", "issue": "", "normalized_date": "2026-08-08", "pages": "107597", "proceedings_title": null, "publisher": "", "title": "Journal of the mechanical behavior of biomedical materials", "volume": "183", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "Computational design for engineering layered tissue architectures via cellular interfacial tension modulation.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Organisms adapt to volatile environments by integrating sensory information with internal memory, yet their information processing is constrained by resource limitations. Such limitations can fundamentally alter optimal estimation strategies in biological systems. For example, recent experiments suggest that organisms exhibit phase transitions between memoryless and memory-based estimation strategies depending on energy availability and sensory reliability. However, a theoretical understanding of how resource limitations induce these transitions is still missing. This Letter presents an analytical characterization of the resource-induced phase transitions in optimal estimation strategies. Our results identify the conditions under which resource limitations alter estimation strategies and analytically reveal the mechanism underlying the emergence of discontinuous, nonmonotonic, and scaling behaviors. These results provide a theoretical foundation for understanding how limited resources shape information processing in biological systems.", "classifications": [ { "id": "Kobayashi", "label": "Group Kobayashi", "parent": "Wakamoto", "type": "group" }, { "id": "Wakamoto", "label": "Team Wakamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Takehiro", "last_name": "Tottori", "name": null }, { "creator_type": "author", "first_name": "Tetsuya J.", "last_name": "Kobayashi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1103/5ynb-7k4v" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "42606441" } }, "mesh": [], "publication": { "conference_name": null, "date": "2026 Jul 31", "date_precision": "day", "issue": "5", "normalized_date": "2026-07-31", "pages": "058401", "proceedings_title": null, "publisher": "", "title": "Physical review letters", "volume": "137", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "Theoretical Analysis of Resource-Induced Phase Transitions in Estimation Strategies.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Small-cell lung cancer (SCLC) is an aggressive malignancy with limited therapeutic options. We previously showed that nicotinic acid riboside (NAR) sustains NAD biosynthesis in vivo and compensates for NAMPT inhibition in SCLC models. Here, we evaluated combining NAMPT inhibition with dietary nicotinic acid (NA) restriction to suppress NAR-dependent NAD biosynthesis. This combination showed enhanced antitumor activity consistent with synthetic lethality in SCLC CDX models and showed robust efficacy in PDX models, including those derived from chemotherapy-refractory tumors. In most CDX models examined, combination therapy showed greater antitumor activity than standard chemotherapy with cisplatin and etoposide. Although we did observe transient leukopenia, the treatment was otherwise better tolerated than chemotherapy, with less impact on body weight and platelet counts. These findings support NAD metabolism-targeted therapy as a promising strategy to treat SCLC.", "classifications": [ { "id": "JPMJCR2123", "label": "JPMJCR2123", "researcher": "Shinya Kuroda", "type": "grant" }, { "id": "Kuroda", "label": "Group Kuroda", "parent": "Kuroda", "type": "group" }, { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Kyoji", "last_name": "Tsurumi", "name": null }, { "creator_type": "author", "first_name": "Miyuki", "last_name": "Nomura", "name": null }, { "creator_type": "author", "first_name": "Mai", "last_name": "Ouchi", "name": null }, { "creator_type": "author", "first_name": "Shigehiro", "last_name": "Yagishita", "name": null }, { "creator_type": "author", "first_name": "Naohiko", "last_name": "Kikuchi", "name": null }, { "creator_type": "author", "first_name": "Taku", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Mami", "last_name": "Morita", "name": null }, { "creator_type": "author", "first_name": "Yoji", "last_name": "Yamashita", "name": null }, { "creator_type": "author", "first_name": "Kayoko", "last_name": "Hayashi", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Akinobu", "last_name": "Hamada", "name": null }, { "creator_type": "author", "first_name": "Tatsuro", "last_name": "Fukuhara", "name": null }, { "creator_type": "author", "first_name": "Nobuhiro", "last_name": "Tanuma", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/cas.70486" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "42521252" } }, "mesh": [], "publication": { "conference_name": null, "date": "2026 Jul 28", "date_precision": "day", "issue": "", "normalized_date": "2026-07-28", "pages": "", "proceedings_title": null, "publisher": "", "title": "Cancer science", "volume": "", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "Nicotinic Acid Restriction Enhances the Therapeutic Benefit of NAMPT Inhibition in Small-Cell Lung Cancer Models.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Drought stress significantly threatens global food security. According to the FAO2024, agriculture absorbs up to 80% of drought impacts. Stomata are vital pores for gas exchange and transpiration in plants. Stomatal closure, which is crucial for drought tolerance, is regulated by ion transport systems. Here, we identify two inhibitors of plasma membrane voltage-dependent potassium (K(+)) channels, NS5806 and UA49, that induce stomatal closure, reduce guard cell K(+) levels, and increase drought resistance in Arabidopsis plants. This chemical-induced stomatal closure pathway is distinct from the abscisic acid (ABA). Notably, K(+) channel inhibition led to increased cytosolic Ca(2+), which was absent in K(+) inward channel mutants, highlighting the link between K(+) channel activity and cytosolic Ca(2+) elevation. These findings suggest that the chemical regulation of K(+) channels represents a strategy to induce stomatal closure, potentially improving plant drought tolerance through targeted interventions.", "classifications": [ { "id": "Higaki", "label": "Group Higaki", "parent": "Ueda", "type": "group" }, { "id": "Ueda", "label": "Team Ueda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Kanane", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Kyota", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Shunya", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Taishin", "last_name": "Kakei", "name": null }, { "creator_type": "author", "first_name": "Megumi", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Masana", "last_name": "Yazaki", "name": null }, { "creator_type": "author", "first_name": "Yasutaka", "last_name": "Kawai", "name": null }, { "creator_type": "author", "first_name": "Mieko", "last_name": "Arisawa", "name": null }, { "creator_type": "author", "first_name": "Nobuhisa", "last_name": "Isaka", "name": null }, { "creator_type": "author", "first_name": "Toshio", "last_name": "Yamaguchi", "name": null }, { "creator_type": "author", "first_name": "Matteo", "last_name": "Grenzi", "name": null }, { "creator_type": "author", "first_name": "Laura", "last_name": "Luoni", "name": null }, { "creator_type": "author", "first_name": "Masaru", "last_name": "Kono", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Hayashi", "name": null }, { "creator_type": "author", "first_name": "Toshinori", "last_name": "Kinoshita", "name": null }, { "creator_type": "author", "first_name": "Farhan", "last_name": "Aziz", "name": null }, { "creator_type": "author", "first_name": "Khurram", "last_name": "Bashir", "name": null }, { "creator_type": "author", "first_name": "Motoaki", "last_name": "Seki", "name": null }, { "creator_type": "author", "first_name": "Asuka", "last_name": "Kamimura", "name": null }, { "creator_type": "author", "first_name": "Takumi", "last_name": "Higaki", "name": null }, { "creator_type": "author", "first_name": "Jun", "last_name": "Takeuchi", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Todoroki", "name": null }, { "creator_type": "author", "first_name": "Huifei", "last_name": "Yin", "name": null }, { "creator_type": "author", "first_name": "Francisco", "last_name": "Rubio", "name": null }, { "creator_type": "author", "first_name": "Jorg", "last_name": "Kudla", "name": null }, { "creator_type": "author", "first_name": "Shintaro", "last_name": "Munemasa", "name": null }, { "creator_type": "author", "first_name": "Yoshiyuki", "last_name": "Murata", "name": null }, { "creator_type": "author", "first_name": "Masaru", "last_name": "Tsujii", "name": null }, { "creator_type": "author", "first_name": "Yasuhiro", "last_name": "Ishimaru", "name": null }, { "creator_type": "author", "first_name": "Alex", "last_name": "Costa", "name": null }, { "creator_type": "author", "first_name": "Nobuyuki", "last_name": "Uozumi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41467-026-75894-w" }, "pmcid": { "normalized": "PMC13408460" }, "pmid": { "normalized": "42509236" } }, "mesh": [ { "descriptor": "Abscisic Acid", "descriptor_ui": "D000040", "major_topic": false }, { "descriptor": "Arabidopsis", "descriptor_ui": "D017360", "major_topic": true }, { "descriptor": "Arabidopsis Proteins", "descriptor_ui": "D029681", "major_topic": false }, { "descriptor": "Calcium", "descriptor_ui": "D002118", "major_topic": false }, { "descriptor": "Drought Resistance", "descriptor_ui": "D000091902", "major_topic": false }, { "descriptor": "Droughts", "descriptor_ui": "D055864", "major_topic": false }, { "descriptor": "Plant Stomata", "descriptor_ui": "D054046", "major_topic": false }, { "descriptor": "Potassium", "descriptor_ui": "D011188", "major_topic": false }, { "descriptor": "Potassium Channel Blockers", "descriptor_ui": "D026902", "major_topic": true }, { "descriptor": "Stress, Physiological", "descriptor_ui": "D013312", "major_topic": false } ], "publication": { "conference_name": null, "date": "2026 Jul 27", "date_precision": "day", "issue": "1", "normalized_date": "2026-07-27", "pages": "", "proceedings_title": null, "publisher": "", "title": "Nature communications", "volume": "17", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "Synthetic ion channel inhibitors enhance plant drought tolerance.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "There is a global need for bioimage analysis (BIA) as advances in life sciences increasingly rely on cutting-edge imaging systems that have dramatically expanded the complexity and dimensionality of biological images. Turning these data into scientific discoveries requires scientists with effective data management skills and knowledge of state-of-the-art image processing and data analysis, in other words, bioimage analysts. The Global BioImage Analysts' Society (GloBIAS) aims to enhance the profile of bioimage analysts as a key role in science and research. To better understand the needs and geographical representation of the BIA community, a worldwide survey was conducted, and 290 responses were collected across people from all career stages and continents. The survey underscores a strong interest of the BIA community in the activities proposed by GloBIAS to address shortcomings in work environment, funding, and scientific activities, and the enthusiasm of the community to actively contribute to the growth and sustainability of GloBIAS as a scientific society.", "classifications": [ { "id": "Onami", "label": "Group Onami", "parent": "Fujiwara", "type": "group" }, { "id": "Fujiwara", "label": "Team Fujiwara", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Laura R.", "last_name": "de la Ballina", "name": null }, { "creator_type": "author", "first_name": "Christa G.", "last_name": "Walther", "name": null }, { "creator_type": "author", "first_name": "Nicholas D.", "last_name": "Condon", "name": null }, { "creator_type": "author", "first_name": "Alessandro A.", "last_name": "Felder", "name": null }, { "creator_type": "author", "first_name": "Martin", "last_name": "Schatz", "name": null }, { "creator_type": "author", "first_name": "Bettina", "last_name": "Schmerl", "name": null }, { "creator_type": "author", "first_name": "Ko", "last_name": "Sugawara", "name": null }, { "creator_type": "author", "first_name": "Clara", "last_name": "Prats", "name": null }, { "creator_type": "author", "first_name": "Anna", "last_name": "Klemm", "name": null }, { "creator_type": "author", "first_name": "Kota", "last_name": "Miura", "name": null }, { "creator_type": "author", "first_name": "Paula", "last_name": "Sampaio", "name": null }, { "creator_type": "author", "first_name": "Christian", "last_name": "Tischer", "name": null }, { "creator_type": "author", "first_name": "Shuichi", "last_name": "Onami", "name": null }, { "creator_type": "author", "first_name": "Rocco", "last_name": "D'Antuono", "name": null }, { "creator_type": "author", "first_name": "Beth A.", "last_name": "Cimini", "name": null }, { "creator_type": "author", "first_name": "Robert", "last_name": "Haase", "name": null }, { "creator_type": "author", "first_name": "Agustin A.", "last_name": "Corbat", "name": null }, { "creator_type": "author", "first_name": "Florian", "last_name": "Levet", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/jmi.70153" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "42504951" } }, "mesh": [], "publication": { "conference_name": null, "date": "2026 Jul 27", "date_precision": "day", "issue": "", "normalized_date": "2026-07-27", "pages": "", "proceedings_title": null, "publisher": "", "title": "Journal of microscopy", "volume": "", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "GloBIAS survey results - An insight into the global bioimage analysis community.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Supersulfides, a class of catenated sulfur-containing biomolecules, are increasingly recognized as key regulators of redox signaling, mitochondrial function, and inflammatory responses. Recent evidence suggests that lysosomes, central organelles for intracellular degradation and nutrient sensing, are closely linked to supersulfide metabolism through lysosomal acidification, cysteine metabolism, and autophagy. Conversely, supersulfides modulate lysosomal activity and inflammatory responses. This review summarizes recent progress in supersulfide biology and lysosomal regulation and discusses evidence supporting functional interactions between these systems. We propose the lysosome-supersulfide axis as a new concept in cellular homeostasis and metabolic regulation.", "classifications": [ { "id": "JPMJCR2024", "label": "JPMJCR2024", "researcher": "Motohiro Nishida", "type": "grant" }, { "id": "Akaike", "label": "Group Akaike", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Group Nishida", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Natsumi", "last_name": "Sakata", "name": null }, { "creator_type": "author", "first_name": "Takaaki", "last_name": "Akaike", "name": null }, { "creator_type": "author", "first_name": "Hozumi", "last_name": "Motohashi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1093/jb/mvag058" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "42496187" } }, "mesh": [], "publication": { "conference_name": null, "date": "2026 Jul 24", "date_precision": "day", "issue": "", "normalized_date": "2026-07-24", "pages": "mvag058", "proceedings_title": null, "publisher": "", "title": "Journal of biochemistry", "volume": "", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "Lysosomes and Supersulfides: Emerging Links in Cellular Metabolism and Homeostasis.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Wavelike motion mediated by chemotactic signaling occurs in various biological phenomena including neutrophil swarms, wound healing, and amoeba aggregates. However, the macroscopic transition from independent to collective cellular behavior remains unclear, including how to quantify the response of individual cells to a developing chemotactic wave. Recent advances in molecular imaging allow concurrent observation of cyclic adenosine monophosphate (cAMP) concentrations and cell movement at individual resolution. Employing particle image velocimetry (PIV), a scheme to extract Eulerian velocity vector fields in fluids, we derived velocity fields at different Gaussian blurring levels and found that while original fluorescent images reflect cell movement, blurred versions highlight cAMP wave propagation. We identified the phase of cAMP signal wave dynamics and analyzed the interplay between single-cell motility and cAMP wave development. The extracted velocity fields at single-cell resolution show an almost antipodal relationship to those of the cAMP wave characterized by the blurred image, with an angle close to 180 degrees during the rise of the wave when the spiral wave is well developed. Furthermore, single-cell dynamics collectively move toward the crest of the coming cAMP wave but rest (with randomized directionality) in the troughs between waves, akin to \"surfing of the collectives\".", "classifications": [ { "id": "Sawai", "label": "Group Sawai", "parent": "Sawai", "type": "group" }, { "id": "Sawai", "label": "Team Sawai", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Sulimon", "last_name": "Sattari", "name": null }, { "creator_type": "author", "first_name": "Md Motaleb", "last_name": "Hossain", "name": null }, { "creator_type": "author", "first_name": "Udoy S.", "last_name": "Basak", "name": null }, { "creator_type": "author", "first_name": "Mikito", "last_name": "Toda", "name": null }, { "creator_type": "author", "first_name": "Takeharu", "last_name": "Nagai", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Sawai", "name": null }, { "creator_type": "author", "first_name": "Kazuki", "last_name": "Horikawa", "name": null }, { "creator_type": "author", "first_name": "Tamiki", "last_name": "Komatsuzaki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41598-026-61774-2" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "42471391" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Movement", "descriptor_ui": "D002465", "major_topic": true }, { "descriptor": "Chemotaxis", "descriptor_ui": "D002633", "major_topic": true }, { "descriptor": "Cyclic AMP", "descriptor_ui": "D000242", "major_topic": false }, { "descriptor": "Rheology", "descriptor_ui": "D012212", "major_topic": false }, { "descriptor": "Single-Cell Analysis", "descriptor_ui": "D059010", "major_topic": true } ], "publication": { "conference_name": null, "date": "2026 Jul 18", "date_precision": "day", "issue": "", "normalized_date": "2026-07-18", "pages": "", "proceedings_title": null, "publisher": "", "title": "Scientific reports", "volume": "", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "Collective surfing of single cells on a chemo-attractant wave using multiscale Eulerian velocity vector field.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Age-related disease burden accumulates heterogeneously from later midlife to older age, but the biology underlying these divergent trajectories is poorly understood. We analysed 7199 adults aged 40 years and over in the Tsuruoka Metabolomics Cohort Study, Japan, with baseline fasting plasma metabolomics (94 metabolites measured by capillary electrophoresis-mass spectrometry) and linked health insurance claims. Monthly cumulative Charlson Comorbidity Index scores were constructed from aligned cohort entry to 60 months to capture accumulation of newly documented Charlson conditions after follow-up start. K-means clustering identified six trajectories of claims-recorded disease burden, and ordinal logistic regression related metabolites to ordered trajectory severity with adjustment for demographic and lifestyle factors. Six trajectories ranged from minimal accumulation to rapid progression. Nineteen metabolites were associated with greater trajectory severity after false discovery rate correction. Glutamate showed the strongest positive association (odds ratio, 1.18 per standard deviation; 95% confidence interval, 1.12-1.24), whereas cysteine-glutathione disulfide showed the strongest inverse association (odds ratio, 0.89; 95% confidence interval, 0.86-0.93). Eighteen of these metabolites were also associated with time to first newly documented Charlson disease. Disease-specific analyses linked glutamate to diabetes with complications, mild liver disease, and cerebrovascular disease. Exploratory cluster-specific analyses identified hippurate as a distinctive marker of a late-acceleration trajectory. These findings implicate amino acid metabolism, redox balance, and microbiome-host interactions as candidate biological pathways underlying heterogeneous patterns of age-related disease accumulation, and warrant replication in independent cohorts. These signals may inform biomarker development for accelerated disease-burden accumulation.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Ryota", "last_name": "Toki", "name": null }, { "creator_type": "author", "first_name": "Chisato", "last_name": "Iba", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Omoto", "name": null }, { "creator_type": "author", "first_name": "Minako", "last_name": "Matsumoto", "name": null }, { "creator_type": "author", "first_name": "Miho", "last_name": "Iida", "name": null }, { "creator_type": "author", "first_name": "Shun", "last_name": "Edagawa", "name": null }, { "creator_type": "author", "first_name": "Sei", "last_name": "Harada", "name": null }, { "creator_type": "author", "first_name": "Aya", "last_name": "Hirata", "name": null }, { "creator_type": "author", "first_name": "Naoko", "last_name": "Miyagawa", "name": null }, { "creator_type": "author", "first_name": "Atsuko", "last_name": "Miyake", "name": null }, { "creator_type": "author", "first_name": "Akiyoshi", "last_name": "Hirayama", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Sugimoto", "name": null }, { "creator_type": "author", "first_name": "Asako", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Kaori", "last_name": "Amano", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Kazuharu", "last_name": "Arakawa", "name": null }, { "creator_type": "author", "first_name": "Toru", "last_name": "Takebayashi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/s11357-026-02408-3" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "42470521" } }, "mesh": [], "publication": { "conference_name": null, "date": "2026 Jul 18", "date_precision": "day", "issue": "", "normalized_date": "2026-07-18", "pages": "", "proceedings_title": null, "publisher": "", "title": "GeroScience", "volume": "", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "Plasma metabolomic signatures of heterogeneous multimorbidity trajectories in ageing: a population-based cohort study.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Liquid-liquid phase separation (LLPS) generates high-concentration biomolecular liquid droplets and contributes to diverse intracellular processes. Intracellular droplets contain not only proteins that drive LLPS but also various coexisting components and abundant hydration water, and their properties depend strongly on both the constituent components and the surrounding intracellular environments. However, the quantitative understanding of these factors within living cells remains limited. Raman microscopy is well suited for this challenge, enabling label-free, direct analysis of structures and concentrations of constituent molecules and hydration water in droplets, while also providing information on intracellular molecular crowding environments. In this review, we summarize recent Raman microscopic studies on intracellular droplets, focusing on coexisting components, structural characterization, hydration water, and their relationships with molecular crowding.", "classifications": [ { "id": "Nakabayashi", "label": "Group Nakabayashi", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Takakazu", "last_name": "Nakabayashi", "name": null }, { "creator_type": "author", "first_name": "Ren", "last_name": "Shibuya", "name": null }, { "creator_type": "author", "first_name": "Shinji", "last_name": "Kajimoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.sbi.2026.103333" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "42468205" } }, "mesh": [], "publication": { "conference_name": null, "date": "2026 Jul 17", "date_precision": "day", "issue": "", "normalized_date": "2026-07-17", "pages": "103333", "proceedings_title": null, "publisher": "", "title": "Current opinion in structural biology", "volume": "100", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "Intracellular biomolecular condensates viewed by Raman microscopy: Composition, crowding, and hydration.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Cellular hydropersulfides (RS-SH) derived from hydrogen sulfide (H(2)S) such as glutathione hydropersulfide (GS-SH) are excellent hydrogen atom transfer agents, and quench radicals to protect cells from ferroptosis, a form of iron-mediated cell death associated with an unchecked build-up of lipid radicals. Here, using principles of enzyme-inhibitor design, a series of new artificial substrates for the endogenous hydropersulfide-generating enzyme, 3-mercaptopyruvate sulfurtransferase (3-MST) was developed. We find that the lead molecules generated GS-SH, catalyzed by 3-MST, permeated cells to enhance endogenous hydropersulfides, protected cells from ferroptosis, and reduced systemic inflammation in an animal model. Together, this calibrated approach to promote cell's own radical trapping antioxidants using its biosynthetic machinery to prevent ferroptosis has tremendous implications in redox biology and therapeutics.", "classifications": [ { "id": "JPMJCR2024", "label": "JPMJCR2024", "researcher": "Motohiro Nishida", "type": "grant" }, { "id": "Akaike", "label": "Group Akaike", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Group Nishida", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Simran M.", "last_name": "Gupta", "name": null }, { "creator_type": "author", "first_name": "Santhosh", "last_name": "Duraisamy", "name": null }, { "creator_type": "author", "first_name": "Tsuyoshi", "last_name": "Takata", "name": null }, { "creator_type": "author", "first_name": "Takaaki", "last_name": "Akaike", "name": null }, { "creator_type": "author", "first_name": "Siddhesh S.", "last_name": "Kamat", "name": null }, { "creator_type": "author", "first_name": "Dharmaraja", "last_name": "Allimuthu", "name": null }, { "creator_type": "author", "first_name": "Harinath", "last_name": "Chakrapani", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/anie.4893359" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "42466747" } }, "mesh": [], "publication": { "conference_name": null, "date": "2026 Jul 17", "date_precision": "day", "issue": "", "normalized_date": "2026-07-17", "pages": "e4893359", "proceedings_title": null, "publisher": "", "title": "Angewandte Chemie (International ed. in English)", "volume": "", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "Engineered Substrates for a Sulfurtransferase Enhance Endogenous Hydropersulfides and Inhibit Ferroptosis.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Total anomalous pulmonary venous connection (TAPVC) is a severe congenital heart disease, yet its prenatal detection rate remains suboptimal. To support prenatal ultrasound screening of TAPVC, the post-left atrium space (PLAS) index and the left-atrial posterior-space-to-diagonal (LAPSD) ratio measured in the four-chamber view (4CV) have been proposed as useful biometric parameters. In this study, we developed a novel approach that integrates automated 4CV extraction (AE) from fetal cardiac ultrasound videos with automated measurement of these indices. The heart, crux, and descending aorta were segmented using DeepLabv3+, UNet3+, and SegFormer. The screening performance of the AE-based methods was comparable to that of manual 4CV extraction, as demonstrated by similar mean areas under the receiver operating characteristic curve (AUCs). In a clinical comparison study, the mean AUC values for residents, fellows, experts, AE-DeepLabv3+, AE-UNet3+, and AE-SegFormer were 0.784, 0.801, 0.996, 0.903, 0.928, and 0.940, respectively, for the PLAS index and 0.797, 0.801, 0.996, 0.919, 0.916, and 0.940, respectively, for the LAPSD ratio. Although experts demonstrated the best overall performance, the fully automated methods consistently outperformed both the residents and fellows. This approach may support less experienced examiners, improve screening accuracy, streamline clinical workflows, and ultimately enhance the prenatal detection of TAPVC.", "classifications": [ { "id": "Hamamoto", "label": "Group Hamamoto", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Rina", "last_name": "Aoyama", "name": null }, { "creator_type": "author", "first_name": "Naoaki", "last_name": "Harada", "name": null }, { "creator_type": "author", "first_name": "Masaaki", "last_name": "Komatsu", "name": null }, { "creator_type": "author", "first_name": "Reina", "last_name": "Komatsu", "name": null }, { "creator_type": "author", "first_name": "Katsuji", "last_name": "Takeda", "name": null }, { "creator_type": "author", "first_name": "Naoki", "last_name": "Teraya", "name": null }, { "creator_type": "author", "first_name": "Ken", "last_name": "Asada", "name": null }, { "creator_type": "author", "first_name": "Syuzo", "last_name": "Kaneko", "name": null }, { "creator_type": "author", "first_name": "Kazuki", "last_name": "Iwamoto", "name": null }, { "creator_type": "author", "first_name": "Ryu", "last_name": "Matsuoka", "name": null }, { "creator_type": "author", "first_name": "Akihiko", "last_name": "Sekizawa", "name": null }, { "creator_type": "author", "first_name": "Ryuji", "last_name": "Hamamoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.3390/bioengineering13070822" }, "pmcid": { "normalized": "PMC13405166" }, "pmid": { "normalized": "42510487" } }, "mesh": [], "publication": { "conference_name": null, "date": "2026 Jul 17", "date_precision": "day", "issue": "7", "normalized_date": "2026-07-17", "pages": "", "proceedings_title": null, "publisher": "", "title": "Bioengineering (Basel, Switzerland)", "volume": "13", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "Fully Automated Biometric Parameter Measurement in Prenatal Ultrasound Screening for Total Anomalous Pulmonary Venous Connection.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "OBJECTIVE: Pathological \"invasion\" influences patient prognosis in lung adenocarcinoma (LUAD); however, diagnosis is often associated with high interobserver variability because non-lepidic adenocarcinoma (NLA) and cancer-related fibrosis (CRF) are intricately mixed, and CRF contains both invasive and non-invasive components. In this study, to enable quantitative and reproducible diagnosis of areas showing high intratumoral heterogeneity, we proposed an artificial intelligence (AI)-based analysis distinguishing between NLA and CRF. This approach could reduce interobserver variability in prognostic prediction and help examine the different biological meanings of NLA and CRF. METHODS: To clarify the physiological structure of lung parenchyma, we used elastin staining specimens. CRF and NLA were separately annotated in the first cohort (n = 35) and used for supervised learning. The AI then analyzed whole non-lepidic areas in the second cohort (n = 188); we then examined the relationship between clinicopathological features and the AI analysis. RESULTS: For the first cohort, the accuracy was 89.2% on average. For the second cohort, groups with high CRF ratios (>50%) in the AI analysis showed a statistical correlation with types B-C in Noguchi's classification (p < 0.001), grades 1-2 in the WHO grading system (p = 0.018), and a higher 5-year disease-free survival (DFS) rate (85.7% vs. 69.4%, p = 0.006). In groups with a low CRF ratio (n = 111), a central distribution of CRF was associated with a lower DFS rate (41.2% vs. 74.5%, p = 0.001). CONCLUSION: The AI engine for distinguishing between NLA and CRF enabled prognostic prediction of LUAD with reduced interobserver variability. It may also be useful for examining the biological significance of NLA and CRF.", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Hitomi", "last_name": "Kawai", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null }, { "creator_type": "author", "first_name": "Akihiko", "last_name": "Yoshizawa", "name": null }, { "creator_type": "author", "first_name": "Yasuhiro", "last_name": "Sakai", "name": null }, { "creator_type": "author", "first_name": "Kohei", "last_name": "Yamashita", "name": null }, { "creator_type": "author", "first_name": "Kazuhiro", "last_name": "Hotta", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Matsubara", "name": null }, { "creator_type": "author", "first_name": "Masayuki", "last_name": "Noguchi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.lungcan.2026.109542" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "42470747" } }, "mesh": [ { "descriptor": "Adenocarcinoma of Lung", "descriptor_ui": "D000077192", "major_topic": true }, { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Artificial Intelligence", "descriptor_ui": "D001185", "major_topic": true }, { "descriptor": "Elastin", "descriptor_ui": "D004549", "major_topic": true }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Fibrosis", "descriptor_ui": "D005355", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Lung Neoplasms", "descriptor_ui": "D008175", "major_topic": true }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Observer Variation", "descriptor_ui": "D015588", "major_topic": false }, { "descriptor": "Prognosis", "descriptor_ui": "D011379", "major_topic": false }, { "descriptor": "Staining and Labeling", "descriptor_ui": "D013194", "major_topic": false } ], "publication": { "conference_name": null, "date": "2026 Jul 17", "date_precision": "day", "issue": "", "normalized_date": "2026-07-17", "pages": "109542", "proceedings_title": null, "publisher": "", "title": "Lung cancer (Amsterdam, Netherlands)", "volume": "219", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "AI analysis of elastin staining sections reveals the biological implications of cancer-related fibrosis in small-sized lung adenocarcinomas.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The impact of the metabolic microenvironment on epigenetically plastic cancer cells underpins phenotypic heterogeneity, a major cause of metastasis and therapy resistance. Nutrient limitation is a key microenvironmental stress, and can cause cells to transition from proliferative to invasive phenotypes, however, whether cancer cells have the capacity to delay phenotype switching remains unknown. Here, using melanoma as a model, we reveal that the ability to buffer glucose availability by accumulating and mobilizing glycogen can determine cancer cell phenotypic transitions. While proliferating cells contain high levels of glycogen, invasive cells are marked by depleted glycogen stores. Accordingly, the inability to store and metabolize glycogen leads to phenotype instability and a switch from proliferation to invasion. The amount of stored glycogen inversely correlates with tissue invasion depth in primary melanomas, and reduced expression of the glycogen phosphorylases PYGB/L and phosphoglucomutase 1 (PGM1) is associated with worse patient survival. Together, we identify metabolic glucose buffering as a determinant of invasive phenotype transitions in skin cancer, suggesting similar paradigms in other cancer types.", "classifications": [ { "id": "JPMJCR2123", "label": "JPMJCR2123", "researcher": "Shinya Kuroda", "type": "grant" }, { "id": "Kuroda", "label": "Group Kuroda", "parent": "Kuroda", "type": "group" }, { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Ana", "last_name": "Ramirez-Sanchez", "name": null }, { "creator_type": "author", "first_name": "Miguel", "last_name": "Jociles-Ortega", "name": null }, { "creator_type": "author", "first_name": "Jose Manuel", "last_name": "Garcia-Martinez", "name": null }, { "creator_type": "author", "first_name": "Irene", "last_name": "Torrens-Martinez", "name": null }, { "creator_type": "author", "first_name": "Javier", "last_name": "Martinez-Useros", "name": null }, { "creator_type": "author", "first_name": "Pakavarin", "last_name": "Louphrasitthiphol", "name": null }, { "creator_type": "author", "first_name": "Mollie I.", "last_name": "Sweeney", "name": null }, { "creator_type": "author", "first_name": "Ana", "last_name": "Morente-Carrasco", "name": null }, { "creator_type": "author", "first_name": "Sergio", "last_name": "Ruiz-Reyes", "name": null }, { "creator_type": "author", "first_name": "Nerea", "last_name": "Redondo-Diaz", "name": null }, { "creator_type": "author", "first_name": "Teresa", "last_name": "Olmos-De Blas", "name": null }, { "creator_type": "author", "first_name": "Maria Jesus", "last_name": "Fernandez-Acenero", "name": null }, { "creator_type": "author", "first_name": "Jose N.", "last_name": "Rodriguez-Lopez", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Richard M.", "last_name": "White", "name": null }, { "creator_type": "author", "first_name": "Colin R.", "last_name": "Goding", "name": null }, { "creator_type": "author", "first_name": "Luis", "last_name": "Sanchez-Del-Campo", "name": null }, { "creator_type": "author", "first_name": "Custodia", "last_name": "Garcia-Jimenez", "name": null }, { "creator_type": "author", "first_name": "Ana", "last_name": "Chocarro-Calvo", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s44318-026-00857-2" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "42458060" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Cell Proliferation", "descriptor_ui": "D049109", "major_topic": false }, { "descriptor": "Glucose", "descriptor_ui": "D005947", "major_topic": true }, { "descriptor": "Glycogen", "descriptor_ui": "D006003", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Melanoma", "descriptor_ui": "D008545", "major_topic": true }, { "descriptor": "Metabolic Reprogramming", "descriptor_ui": "D000097784", "major_topic": false }, { "descriptor": "Neoplasm Invasiveness", "descriptor_ui": "D009361", "major_topic": false }, { "descriptor": "Phenotype", "descriptor_ui": "D010641", "major_topic": false }, { "descriptor": "Phosphoglucomutase", "descriptor_ui": "D010733", "major_topic": false }, { "descriptor": "Skin Neoplasms", "descriptor_ui": "D012878", "major_topic": true } ], "publication": { "conference_name": null, "date": "2026 Jul 15", "date_precision": "day", "issue": "", "normalized_date": "2026-07-15", "pages": "", "proceedings_title": null, "publisher": "", "title": "The EMBO journal", "volume": "", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "Metabolic buffering restricts phenotype switching in melanoma.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Alginate hydrogels are highly valuable for a variety of biomedical applications, such as scaffolds for tissue engineering and carriers for cell therapy. Alginate, a natural polysaccharide derived from brown algae, is unique for its ability to form a hydrogel in the presence of Ca(2+) and is biocompatible and biodegradable. There is an unmet need for robust detection of hydrogels after implantation in cell-based therapies. In this study, we tested the feasibility of using Raman spectroscopy to detect alginate signatures and spatially mapping alginate in cryosectioned tissue samples following implantation of alginate scaffolds both with and without cells. We first characterized and validated Raman spectra of alginate. Then, we performed Raman spectroscopy on cell-laden alginate hydrogel microstrands that allow for high-density cell delivery. Furthermore, we used cyrosectioned mouse salivary gland tissue samples containing cell-laden alginate microstrands, which were prepared after in vivo implantation for 14 days, for Raman spectroscopy studies. We aimed to detect alginate and distinguish alginate in these tissue cryosections. We identified a region in the Raman spectra where alginate exhibited stronger signals than the tissue or freezing media. Specific Raman peaks at 816, 888, 959, 1300, and 1433 cm(-1) were associated with alginate. By analyzing Raman spectra from samples containing alginate, cells, tissue, and freezing media, we were able to distinguish alginate from the other components using either characteristic spectral peaks or Classical Least Squares (CLS) analysis. Additionally, we applied high-resolution mapping using line scanning Raman microscopy, demonstrating the capacity of spatial mapping of alginate in cryosectioned salivary gland tissue samples at the molecular level. The high sensitivity and specificity of Raman spectroscopy make it a promising tool for identifying engineered materials in tissue engineering applications.", "classifications": [ { "id": "Fujita", "label": "Group Fujita", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Monireh", "last_name": "Pourrahimi", "name": null }, { "creator_type": "author", "first_name": "Rafael", "last_name": "Pena", "name": null }, { "creator_type": "author", "first_name": "Sujith Chander Reddy", "last_name": "Kollampally", "name": null }, { "creator_type": "author", "first_name": "Tomoaki", "last_name": "Okumura", "name": null }, { "creator_type": "author", "first_name": "Samaneh", "last_name": "Ghazanfarpour", "name": null }, { "creator_type": "author", "first_name": "Alireza", "last_name": "Sheikhsofla", "name": null }, { "creator_type": "author", "first_name": "Deidre", "last_name": "Nelson", "name": null }, { "creator_type": "author", "first_name": "Anna", "last_name": "Sharikova", "name": null }, { "creator_type": "author", "first_name": "Katsumasa", "last_name": "Fujita", "name": null }, { "creator_type": "author", "first_name": "Jennifer M.", "last_name": "Morrissey", "name": null }, { "creator_type": "author", "first_name": "Yubing", "last_name": "Xie", "name": null }, { "creator_type": "author", "first_name": "Melinda", "last_name": "Larsen", "name": null }, { "creator_type": "author", "first_name": "Alexander", "last_name": "Khmaladze", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.bioadv.2026.215060" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "42470815" } }, "mesh": [ { "descriptor": "Alginates", "descriptor_ui": "D000464", "major_topic": true }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Glucuronic Acid", "descriptor_ui": "D020723", "major_topic": false }, { "descriptor": "Hexuronic Acids", "descriptor_ui": "D006603", "major_topic": false }, { "descriptor": "Hydrogels", "descriptor_ui": "D020100", "major_topic": true }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Spectrum Analysis, Raman", "descriptor_ui": "D013059", "major_topic": true }, { "descriptor": "Tissue Engineering", "descriptor_ui": "D023822", "major_topic": false }, { "descriptor": "Tissue Scaffolds", "descriptor_ui": "D054457", "major_topic": false } ], "publication": { "conference_name": null, "date": "2026 Jul 12", "date_precision": "day", "issue": "", "normalized_date": "2026-07-12", "pages": "215060", "proceedings_title": null, "publisher": "", "title": "Biomaterials advances", "volume": "188", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "Robust detection and high-resolution mapping of implanted alginate hydrogels in tissue with Raman spectroscopy.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: Sustained attention requires continuous engagement and is sensitive to individual differences in motivational processes. Variability in sustained attention is commonly observed across individuals and can manifest as fluctuations in attentional stability during prolonged tasks. Such variability may reflect inattentive traits associated with attention-deficit/hyperactivity disorder (ADHD), which are continuously distributed across the general population. The habenula is a subcortical structure involved in motivation- and reward-related regulation, yet its contribution to individual differences in sustained attention remains unclear. This study examined whether habenular morphology is associated with dimensional ADHD-related inattentive traits and reaction-time variability during sustained attention. METHODS: In 151 healthy adults (excluding high ADHD symptoms), we assessed self-reported ADHD symptoms and autistic traits, and measured sustained attention using a computerized visual processing task. Habenula volumes were quantified using 7-Tesla MRI with a deep-learning-based segmentation pipeline. Mediation analyses tested whether self-reported inattention and RVP SD latency were statistically linked via TIV-normalized relative habenula volume, controlling for age, sex, education, and autistic traits. RESULTS: Inattention scores were positively associated with relative habenula volume, whereas hyperactivity-impulsivity showed no such relationship. Larger relative habenula volume was associated with greater reaction-time variability (standard deviation [SD] latency). AQ total score was not significantly associated with relative total habenula volume or RVP SD latency. Mediation analysis identified a significant indirect statistical association linking inattention and SD latency via relative total habenula volume (ACME = 0.044, p = 0.032), independent of autistic traits, even in the absence of a significant total effect. CONCLUSION: Larger relative total habenula volume was associated with an indirect statistical link between self-reported inattention and reaction-time variability during sustained attention.", "classifications": [ { "id": "Fujiwara", "label": "Group Fujiwara", "parent": "Fujiwara", "type": "group" }, { "id": "Fujiwara", "label": "Team Fujiwara", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Risa", "last_name": "Hirata", "name": null }, { "creator_type": "author", "first_name": "Naoya", "last_name": "Oishi", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Kyuragi", "name": null }, { "creator_type": "author", "first_name": "Halwa", "last_name": "Zakia", "name": null }, { "creator_type": "author", "first_name": "Morio", "last_name": "Aki", "name": null }, { "creator_type": "author", "first_name": "Sayaka", "last_name": "Yoshimura", "name": null }, { "creator_type": "author", "first_name": "Mami", "last_name": "Shibata", "name": null }, { "creator_type": "author", "first_name": "Nagara", "last_name": "Takao", "name": null }, { "creator_type": "author", "first_name": "Saki", "last_name": "Akahori", "name": null }, { "creator_type": "author", "first_name": "Kei", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Toshiya", "last_name": "Murai", "name": null }, { "creator_type": "author", "first_name": "Hironobu", "last_name": "Fujiwara", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.neuroimage.2026.122125" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "42431563" } }, "mesh": [ { "descriptor": "Adolescent", "descriptor_ui": "D000293", "major_topic": false }, { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Attention", "descriptor_ui": "D001288", "major_topic": true }, { "descriptor": "Attention Deficit Disorder with Hyperactivity", "descriptor_ui": "D001289", "major_topic": true }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Habenula", "descriptor_ui": "D019262", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Magnetic Resonance Imaging", "descriptor_ui": "D008279", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Reaction Time", "descriptor_ui": "D011930", "major_topic": false }, { "descriptor": "Young Adult", "descriptor_ui": "D055815", "major_topic": false } ], "publication": { "conference_name": null, "date": "2026 Jul 10", "date_precision": "day", "issue": "", "normalized_date": "2026-07-10", "pages": "122125", "proceedings_title": null, "publisher": "", "title": "NeuroImage", "volume": "", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "Habenula as a neural mediator of inattentive traits and sustained attention variability: A 7-Tesla magnetic resonance imaging study.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Three-dimensional covalent organic frameworks (3D COFs) are promising crystalline porous materials, but the elucidation of their structure remains challenging, particularly for those featuring spiroborate linkages. Herein, we report the synthesis of a 3D crystalline COF with nbo topology, constructed from a rigid square-planar monomer, tetracyclopentatetraphenylene (TCTP), and spiroborate linkages. Theoretical calculations revealed that the TCTP core has higher rigidity than phthalocyanine, effectively suppressing structural fluctuations during framework formation. The structure of the resulting TCTP-COF was successfully determined using microcrystal electron diffraction (MicroED), revealing a noninterpenetrated cubic framework. TCTP-COF exhibits high crystallinity, thermal stability up to 320 degrees C, and permanent porosity with a Brunauer-Emmett-Teller surface area of 1360 square meters per gram. This work represents the structural determination of a spiroborate-linked 3D crystalline COF using MicroED methods, providing a design strategy for expanding the chemical space of highly ordered 3D COF architectures.", "classifications": [ { "id": "Hijikata", "label": "Group Hijikata", "parent": "Tsuchiya", "type": "group" }, { "id": "Tsuchiya", "label": "Team Tsuchiya", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Soshi", "last_name": "Hirota", "name": null }, { "creator_type": "author", "first_name": "Haruki", "last_name": "Sugiyama", "name": null }, { "creator_type": "author", "first_name": "Nao", "last_name": "Hirata", "name": null }, { "creator_type": "author", "first_name": "Sachiko", "last_name": "Nakano", "name": null }, { "creator_type": "author", "first_name": "Junichi", "last_name": "Usuba", "name": null }, { "creator_type": "author", "first_name": "Yuh", "last_name": "Hijikata", "name": null }, { "creator_type": "author", "first_name": "Ryotaro", "last_name": "Matsuda", "name": null }, { "creator_type": "author", "first_name": "Takanori", "last_name": "Nakane", "name": null }, { "creator_type": "author", "first_name": "Akihiro", "last_name": "Kawamoto", "name": null }, { "creator_type": "author", "first_name": "Genji", "last_name": "Kurisu", "name": null }, { "creator_type": "author", "first_name": "Yasutomo", "last_name": "Segawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1126/sciadv.aeg6230" }, "pmcid": { "normalized": "PMC13353416" }, "pmid": { "normalized": "42430476" } }, "mesh": [], "publication": { "conference_name": null, "date": "2026 Jul 10", "date_precision": "day", "issue": "28", "normalized_date": "2026-07-10", "pages": "eaeg6230", "proceedings_title": null, "publisher": "", "title": "Science advances", "volume": "12", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "Crystalline 3D covalent organic frameworks with nbo topology.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Cancer genome analysis relies on standard human reference genomes, but detecting somatic alterations in highly repetitive or individual-specific regions remains challenging. We developed the Personalized Reference genome-based Cancer Genome Analysis Pipeline (PRCGAP, https://github.com/yos-sk/PRCGAP), to our knowledge, the first comprehensive pipeline integrating haplotype-resolved analyses of somatic point mutations, structural variants, copy number, and DNA methylation on personalized diploid reference genomes, with each variant phased and annotated by genomic features. We applied PRCGAP to eight tumor-normal cell line pairs and three newly collected pediatric B-cell acute lymphoblastic leukemia (B-ALL) clinical samples. PRCGAP recovered most standard reference-based variants (86.7-96.4% across variant types), validated by orthogonal short-read sequencing, while additionally detecting variants that standard references missed (23.4% of SNVs and 32.6% of SVs). Notably, PRCGAP uncovered variants in centromeric and telomeric regions, and somatic single-nucleotide variants were enriched in centromere dip regions, the putative kinetochore formation sites. Using PRCGAP outputs, we identified L1 retrotransposition source sites absent from standard references and showed that a B-ALL IGH::DUX4 fusion arose from a DUX4 pseudogene within an internal D4Z4 repeat unit, rather than the canonical full-length DUX4 gene. Within a single haplotype-resolved framework, PRCGAP opens regions of the cancer genome that are inaccessible to standard references.", "classifications": [ { "id": "Yamamoto", "label": "Group Yamamoto", "parent": "Toyoshima", "type": "group" }, { "id": "Toyoshima", "label": "Team Toyoshima", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yoshitaka", "last_name": "Sakamoto", "name": null }, { "creator_type": "author", "first_name": "Yotaro", "last_name": "Ochi", "name": null }, { "creator_type": "author", "first_name": "Yasunori", "last_name": "Kogure", "name": null }, { "creator_type": "author", "first_name": "Shota", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Aiko", "last_name": "Sato-Otsubo", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Sugawa", "name": null }, { "creator_type": "author", "first_name": "Yosuke", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Taro", "last_name": "Tsujimura", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Mikami", "name": null }, { "creator_type": "author", "first_name": "Genta", "last_name": "Nagae", "name": null }, { "creator_type": "author", "first_name": "Kenichi", "last_name": "Chiba", "name": null }, { "creator_type": "author", "first_name": "Ai", "last_name": "Okada", "name": null }, { "creator_type": "author", "first_name": "Yu", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Hajime", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Aburatani", "name": null }, { "creator_type": "author", "first_name": "Yuhki", "last_name": "Koga", "name": null }, { "creator_type": "author", "first_name": "Itaru", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Junko", "last_name": "Takita", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Mano", "name": null }, { "creator_type": "author", "first_name": "Seishi", "last_name": "Ogawa", "name": null }, { "creator_type": "author", "first_name": "Keisuke", "last_name": "Kataoka", "name": null }, { "creator_type": "author", "first_name": "Motohiro", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Yuichi", "last_name": "Shiraishi", "name": null } ], "identifiers": { "doi": { "normalized": "10.64898/2026.05.28.728591" }, "pmcid": { "normalized": null }, "pmid": { "normalized": null } }, "mesh": [], "publication": { "conference_name": null, "date": "2026 Jul 9", "date_precision": "day", "issue": null, "normalized_date": "2026-07-09", "pages": null, "proceedings_title": null, "publisher": null, "title": null, "volume": null, "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "Personalized reference genome-based pipeline reveals comprehensive haplotype-resolved views of cancer genomes.", "url": "", "zotero": { "item_type": "preprint" } }, { "abstract": "Animals balance staying in a favorable environment with exploring new ones. In C. elegans chemotaxis, the process by which worms migrate toward an attractant has been extensively studied. However, what happens after they reach it remains largely unexplored, partly because conventional assays immobilize worms at the point of arrival. Here, we quantitatively analyzed chemotactic behavior upon reaching an attractive odor source using an immobilization-free chemotaxis assay. We observed that 62% animals left the isoamyl alcohol region after initially approaching it, a behavior we termed \"leaving behavior.\" Quantitative analysis revealed that leaving behavior represents a distinct locomotor state compared with free-moving, high-concentration odor avoidance, and approach behavior. To test whether leaving behavior is related to olfactory adaptation, we analyzed mutants in adaptation-related genes. The proportion of leaving behavior was significantly increased in egl-4 loss-of-function mutants compared with wild-type animals, whereas arr-1 mutants showed no significant difference. These results suggest that egl-4 negatively regulates leaving behavior, suggesting a role for this kinase in stabilizing post-arrival behavioral states beyond its known function in olfactory adaptation. Our findings indicate that chemotaxis involves dynamic behavioral transitions even after reaching an attractant, consistent with an exploration-exploitation trade-off framework.", "classifications": [ { "id": "Onami", "label": "Group Onami", "parent": "Fujiwara", "type": "group" }, { "id": "Fujiwara", "label": "Team Fujiwara", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Shiori", "last_name": "Onoue", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Kyoda", "name": null }, { "creator_type": "author", "first_name": "Shuichi", "last_name": "Onami", "name": null } ], "identifiers": { "doi": { "normalized": "10.64898/2026.07.01.734387" }, "pmcid": { "normalized": null }, "pmid": { "normalized": null } }, "mesh": [], "publication": { "conference_name": null, "date": "2026 Jul 7", "date_precision": "day", "issue": null, "normalized_date": "2026-07-07", "pages": null, "proceedings_title": null, "publisher": null, "title": null, "volume": null, "year": 2026 }, "ssbd": { "database": [], "repository": [ "ssbd-repos-000504" ] }, "title": "Immobilization-free chemotaxis analysis reveals the novel behavioral mode of \"leaving\" in Caenorhabditis elegans.", "url": "", "zotero": { "item_type": "preprint" } }, { "abstract": "", "classifications": [ { "id": "JPMJCR1924", "label": "JPMJCR1924", "researcher": "Yuichiro Tsuchiya", "type": "grant" }, { "id": "Sato", "label": "Group Sato", "parent": "Tsuchiya", "type": "group" }, { "id": "Tsuchiya", "label": "Group Tsuchiya", "parent": "Tsuchiya", "type": "group" }, { "id": "Tsuchiya", "label": "Team Tsuchiya", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Tsuyoshi", "last_name": "Aoyama", "name": null }, { "creator_type": "author", "first_name": "Nagisa", "last_name": "Sugimoto", "name": null }, { "creator_type": "author", "first_name": "Yoshikatsu", "last_name": "Sato", "name": null } ], "identifiers": { "doi": { "normalized": "10.1093/plphys/kiag475" }, "pmcid": { "normalized": "PMC13421888" }, "pmid": { "normalized": "42531100" } }, "mesh": [], "publication": { "conference_name": null, "date": "2026 Jul 2", "date_precision": "day", "issue": "3", "normalized_date": "2026-07-02", "pages": "", "proceedings_title": null, "publisher": "", "title": "Plant physiology", "volume": "201", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "Fluorescence lifetime-based multiplex imaging in living plant cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The selection of the appropriate energy substrate under different physiological conditions is a key aspect of the energy metabolism homeostasis. We here show that Nos1 (nitric oxide synthase 1)-expressing cells in the paraventricular hypothalamic nucleus (PVH) serve as a pivotal node for controlling whole-body fat consumption in male mice. Nos1 neurons account for ~30% of PVH neurons that convey signals via polysynaptic pathways to individual peripheral tissues, including skeletal muscle and brown (BAT) and white (WAT) adipose tissues. Activation of these Nos1 neurons in the PVH area induces WAT lipolysis and fat oxidation in other peripheral tissues via the sympathetic nervous system, thereby increasing whole-body fat consumption. Inhibition of these neurons abolishes the increase in fat consumption during the light period, whereas long-term silencing lead to obesity independent of energy intake. These neurons are also necessary for cold-induced thermogenesis in BAT and the rapid increase in fat consumption elicited by food deprivation or other stressors. Nos1 neurons in the PVH area are therefore essential for controlling fat consumption and energy homeostasis.", "classifications": [ { "id": "Inaba", "label": "Group Inaba", "parent": "Kuroda", "type": "group" }, { "id": "Miyamichi", "label": "Group Miyamichi", "parent": "Enomoto", "type": "group" }, { "id": "Enomoto", "label": "Team Enomoto", "type": "team" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Kunio", "last_name": "Kondoh", "name": null }, { "creator_type": "author", "first_name": "Emi", "last_name": "Hashiuchi", "name": null }, { "creator_type": "author", "first_name": "Yuka", "last_name": "Inaba", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Inoue", "name": null }, { "creator_type": "author", "first_name": "Serika", "last_name": "Yamada", "name": null }, { "creator_type": "author", "first_name": "Kazunari", "last_name": "Miyamichi", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Yoshimura", "name": null }, { "creator_type": "author", "first_name": "Ken-Ichiro", "last_name": "Nakajima", "name": null }, { "creator_type": "author", "first_name": "Takeshi Y.", "last_name": "Hiyama", "name": null }, { "creator_type": "author", "first_name": "Yasuhiko", "last_name": "Minokoshi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41467-026-74362-9" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "42373618" } }, "mesh": [ { "descriptor": "Adipose Tissue, Brown", "descriptor_ui": "D002001", "major_topic": false }, { "descriptor": "Adipose Tissue, White", "descriptor_ui": "D052436", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Energy Metabolism", "descriptor_ui": "D004734", "major_topic": false }, { "descriptor": "Lipid Metabolism", "descriptor_ui": "D050356", "major_topic": true }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Muscle, Skeletal", "descriptor_ui": "D018482", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": true }, { "descriptor": "Nitric Oxide Synthase Type I", "descriptor_ui": "D052248", "major_topic": true }, { "descriptor": "Obesity", "descriptor_ui": "D009765", "major_topic": false }, { "descriptor": "Paraventricular Hypothalamic Nucleus", "descriptor_ui": "D010286", "major_topic": true }, { "descriptor": "Sympathetic Nervous System", "descriptor_ui": "D013564", "major_topic": true }, { "descriptor": "Thermogenesis", "descriptor_ui": "D022722", "major_topic": false } ], "publication": { "conference_name": null, "date": "2026 Jun 29", "date_precision": "day", "issue": "", "normalized_date": "2026-06-29", "pages": "", "proceedings_title": null, "publisher": "", "title": "Nature communications", "volume": "", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "Nos1 neurons in the paraventricular hypothalamic area modulate lipid metabolism via the sympathetic nervous system in male mice.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Osteosarcomas preferentially arise in the metaphysis of juvenile long bones, near the growth plate, unlike most cancers, whose incidence increases with age. Here, we show that p21, a negative regulator of the cell cycle, is induced in proliferating juvenile metaphyseal osteoblasts in response to DNA replication-associated damage. Single-cell RNA sequencing defines a differentiation hierarchy from multipotent progenitors to mature osteoblasts and identifies immature osteoblasts enriched for proliferation and replication stress responses. p21-positive metaphyseal osteoblasts associate with growth plate Indian hedgehog expression and decline after growth plate maturation or Hedgehog inhibition. c-Myc induction selectively promotes juvenile osteoblast proliferation despite p53 activation, but this proliferative response remains Hedgehog-dependent and ceases after growth plate maturation. By contrast, p53 inactivation enables sustained Hedgehog-independent proliferation of c-Myc-induced osteoblasts and lung metastasis. These findings reveal juvenile metaphyseal tissue homeostasis as a potential basis for the age of onset, anatomical specificity, and mutational profile of human osteosarcomas.", "classifications": [ { "id": "Yamamoto", "label": "Group Yamamoto", "parent": "Toyoshima", "type": "group" }, { "id": "Toyoshima", "label": "Team Toyoshima", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Masato", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Fumie", "last_name": "Nakasuka", "name": null }, { "creator_type": "author", "first_name": "Nao", "last_name": "Sankoda", "name": null }, { "creator_type": "author", "first_name": "Yihan", "last_name": "Wang", "name": null }, { "creator_type": "author", "first_name": "Jumpei", "last_name": "Taguchi", "name": null }, { "creator_type": "author", "first_name": "Sho", "last_name": "Ohta", "name": null }, { "creator_type": "author", "first_name": "Yosuke", "last_name": "Yamada", "name": null }, { "creator_type": "author", "first_name": "Manabu", "last_name": "Ozawa", "name": null }, { "creator_type": "author", "first_name": "Satoko", "last_name": "Sakurai", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Kondo", "name": null }, { "creator_type": "author", "first_name": "Tetsuo", "last_name": "Ushiku", "name": null }, { "creator_type": "author", "first_name": "Robert", "last_name": "Nakayama", "name": null }, { "creator_type": "author", "first_name": "Masaya", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Takayanagi", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Shibata", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Yasuhiro", "last_name": "Yamada", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41467-026-74929-6" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "42363015" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Bone Neoplasms", "descriptor_ui": "D001859", "major_topic": true }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Cell Proliferation", "descriptor_ui": "D049109", "major_topic": false }, { "descriptor": "Cyclin-Dependent Kinase Inhibitor p21", "descriptor_ui": "D050759", "major_topic": false }, { "descriptor": "Growth Plate", "descriptor_ui": "D006132", "major_topic": true }, { "descriptor": "Hedgehog Proteins", "descriptor_ui": "D053823", "major_topic": false }, { "descriptor": "Homeostasis", "descriptor_ui": "D006706", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Osteoblasts", "descriptor_ui": "D010006", "major_topic": false }, { "descriptor": "Osteosarcoma", "descriptor_ui": "D012516", "major_topic": true }, { "descriptor": "Proto-Oncogene Proteins c-myc", "descriptor_ui": "D016271", "major_topic": false }, { "descriptor": "Tumor Suppressor Protein p53", "descriptor_ui": "D016159", "major_topic": false } ], "publication": { "conference_name": null, "date": "2026 Jun 26", "date_precision": "day", "issue": "", "normalized_date": "2026-06-26", "pages": "", "proceedings_title": null, "publisher": "", "title": "Nature communications", "volume": "", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "Inherent tissue homeostasis of the juvenile metaphysis provides a foundation for osteosarcoma development.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Alzheimer's disease (AD) is a neurocognitive disorder characterized by the accumulation of amyloid beta (Abeta) in senile plaques in the brain. Abeta accumulates in nerve cells, causing cellular dysfunction through various mechanisms, including mitochondrial dysfunction, leading to apoptosis. AD cell models are being studied to elucidate the neurotoxic effect of Abeta; however, conventional methods such as immunostaining and fluorescent molecular labeling require extensive sample manipulation and may produce artifacts not reflective of natural states. In this study, we employed Raman microscopy on AD cell models and simultaneously detected Abeta accumulated in cells and associated mitochondrial dysfunction through cytochrome distribution changes. This label-free method enables the observation of AD cell models in a more natural state and is expected to contribute to elucidating the mechanism of cell damage caused by Abeta. Furthermore, applying this system to experiments involving Abeta inhibitor administration enables rapid, label-free evaluation of drug activity, which is highly valuable in drug development.", "classifications": [ { "id": "Fujita", "label": "Group Fujita", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yusuke", "last_name": "Mitsuoka", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Morimoto", "name": null }, { "creator_type": "author", "first_name": "Kazuki", "last_name": "Bando", "name": null }, { "creator_type": "author", "first_name": "Susumu", "last_name": "Hara", "name": null }, { "creator_type": "author", "first_name": "Katsumasa", "last_name": "Fujita", "name": null }, { "creator_type": "author", "first_name": "Kohji", "last_name": "Nishida", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/acs.analchem.5c06200" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "42336352" } }, "mesh": [ { "descriptor": "Alzheimer Disease", "descriptor_ui": "D000544", "major_topic": true }, { "descriptor": "Amyloid beta-Peptides", "descriptor_ui": "D016229", "major_topic": true }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Microscopy", "descriptor_ui": "D008853", "major_topic": true }, { "descriptor": "Mitochondria", "descriptor_ui": "D008928", "major_topic": true }, { "descriptor": "Spectrum Analysis, Raman", "descriptor_ui": "D013059", "major_topic": true } ], "publication": { "conference_name": null, "date": "2026 Jun 23", "date_precision": "day", "issue": "", "normalized_date": "2026-06-23", "pages": "", "proceedings_title": null, "publisher": "", "title": "Analytical chemistry", "volume": "", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "Label-Free Detection of Cellular Abeta Accumulation and Mitochondrial Dysfunction in AD Cell Models via Raman Microscopy.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "As part of a Global BioImage Analysts' Society (GloBIAS) initiative, we evaluated the reproducibility of a Graph Neural Network (GNN) study on cell dynamics using structured, community-developed checklists from the Quality Assessment and Reproducibility for Instruments and Images in Light Microscopy (QUAREP-LiMi) initiative. Notably, these checklists were published after the 2022 Target Paper, meaning our assessment is necessarily retrospective. Our assessment revealed a gap between recent reporting standards and practical execution. Reproduction attempts across multiple environments confirmed deficiencies, including the absence of explicit image metadata (pixel size and timestamps), which limits quantitative interpretation. Furthermore, the absence of a software container, which was typical for the time of publication and the incomplete dependency list, necessitated complex manual environment configuration, increasing the barrier to entry. This experience highlights the contrast between the reproducibility expectations at the time and newer standards achieved by minimal compliance and true functional access. We conclude by presenting a detailed discussion of the broader implications for the quantitative biology community and propose actionable recommendations including robust environment containerisation and standardised data deposition to ensure complex computational workflows become scientifically sound and reusable resources. This retrospective case study evaluates a legacy computational paper against modern reproducibility framework, not to critique past non-compliance, but to extract actionable lessons for future research standards.", "classifications": [ { "id": "JPMJCR1926", "label": "JPMJCR1926", "researcher": "Hironobu Fujiwara", "type": "grant" }, { "id": "Fujiwara", "label": "Group Fujiwara", "parent": "Fujiwara", "type": "group" }, { "id": "Fujiwara", "label": "Team Fujiwara", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Martin", "last_name": "Schatz", "name": null }, { "creator_type": "author", "first_name": "Ko", "last_name": "Sugawara", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/jmi.70139" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "42333906" } }, "mesh": [], "publication": { "conference_name": null, "date": "2026 Jun 23", "date_precision": "day", "issue": "", "normalized_date": "2026-06-23", "pages": "", "proceedings_title": null, "publisher": "", "title": "Journal of microscopy", "volume": "", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "The reproducibility gap in graph neural network workflows for cell dynamics: A checklist-driven case study.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: The metabolic landscape of biliary tract cancer (BTC) remains poorly characterized. This study aimed to identify tumor-specific metabolic alterations in BTC using paired tumor and adjacent normal tissues. METHODS: Metabolomic profiling was performed on paired tumor and adjacent normal tissues from 71 patients with BTC using capillary electrophoresis time-of-flight mass spectrometry. Differential metabolites were identified using paired statistical analysis with false discovery rate correction. Pathway enrichment analysis was conducted using the Kyoto Encyclopedia of Genes and Genomes database. RESULTS: Seventeen metabolites were significantly altered between tumor and normal tissues. Pathway analysis identified glycerophospholipid metabolism as the most enriched pathway, driven by water-soluble precursor and intermediate metabolites, including phosphorylcholine, CDP-choline, and ethanolamine phosphate. Hierarchical clustering demonstrated partially distinct metabolic patterns between tumor and normal tissues, with substantial inter-sample variability observed among tumor samples. Metabolites related to amino sugar and nucleotide sugar metabolism were also increased in tumor tissues. Additional pathways, including nicotinate and nicotinamide metabolism and arginine and proline metabolism, were also enriched. Principal component analysis showed partial separation between tumor and normal samples, indicating global metabolic differences between the two groups. These findings indicate metabolic alterations across multiple pathways in BTC. CONCLUSIONS: Paired tissue metabolomics revealed coordinated metabolic alterations in BTC involving choline phospholipid precursor metabolism, amino sugar and nucleotide sugar metabolism, and additional amino acid-related pathways. These results highlight the presence of broad metabolic reprogramming in BTC and underscore the importance of tissue-based metabolomic profiling for characterizing tumor metabolism.", "classifications": [ { "id": "JPMJCR2123", "label": "JPMJCR2123", "researcher": "Shinya Kuroda", "type": "grant" }, { "id": "Kuroda", "label": "Group Kuroda", "parent": "Kuroda", "type": "group" }, { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Hironobu", "last_name": "Suto", "name": null }, { "creator_type": "author", "first_name": "Kensuke", "last_name": "Kumamoto", "name": null }, { "creator_type": "author", "first_name": "Mina", "last_name": "Nagao", "name": null }, { "creator_type": "author", "first_name": "Yumi", "last_name": "Furuichi", "name": null }, { "creator_type": "author", "first_name": "Takuro", "last_name": "Fuke", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Matsukawa", "name": null }, { "creator_type": "author", "first_name": "Yasuhisa", "last_name": "Ando", "name": null }, { "creator_type": "author", "first_name": "Minoru", "last_name": "Oshima", "name": null }, { "creator_type": "author", "first_name": "Kiyoyuki", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Hideki", "last_name": "Kobara", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Keiichi", "last_name": "Okano", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/s00535-026-02471-9" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "42329389" } }, "mesh": [], "publication": { "conference_name": null, "date": "2026 Jun 22", "date_precision": "day", "issue": "", "normalized_date": "2026-06-22", "pages": "", "proceedings_title": null, "publisher": "", "title": "Journal of gastroenterology", "volume": "", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "Paired tumor-normal metabolomic profiling reveals alterations in choline phospholipid precursor metabolism in biliary tract cancer.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Striga hermonthica, a root parasitic weed that infests a diverse range of crops, germinates through the perception of host-derived strigolactones (SLs) with receptor protein ShHTL. The development of effective strategies to suppress Striga represents an urgent challenge in combating poverty and starvation in Africa. We conducted high throughput screening to identify inhibitors for SL receptor in Striga. Through the screening of 800 compounds against eight receptor proteins (ShHTL4-11), 22 compounds were discovered as the ShHTL antagonist. Striga germination assay revealed that one out of 22 compounds has inhibitory activity to SL-induced Striga germination. Structure-activity relationship study of the primary hit compound afforded the Striga germination modulator (SGM-3) with higher potency. In vitro binding assay demonstrated that SGM-3 selectively binds to ShHTL7 which is known as the dominant receptor for Striga seed germination. SGM-3 will contribute to the suppression of Striga infection and elucidation of the parasitization mechanism.", "classifications": [ { "id": "Tsuchiya", "label": "Group Tsuchiya", "parent": "Tsuchiya", "type": "group" }, { "id": "Tsuchiya", "label": "Team Tsuchiya", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Michio", "last_name": "Kuruma", "name": null }, { "creator_type": "author", "first_name": "Masahiko", "last_name": "Yoshimura", "name": null }, { "creator_type": "author", "first_name": "Yuichiro", "last_name": "Tsuchiya", "name": null }, { "creator_type": "author", "first_name": "Ayato", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Yuta", "last_name": "Uchiyama", "name": null }, { "creator_type": "author", "first_name": "Yoshiya", "last_name": "Seto", "name": null }, { "creator_type": "author", "first_name": "Kenichiro", "last_name": "Itami", "name": null }, { "creator_type": "author", "first_name": "Shuhei", "last_name": "Kusano", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Hagihara", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/prechem.5c00283" }, "pmcid": { "normalized": "PMC13292090" }, "pmid": { "normalized": "42359039" } }, "mesh": [], "publication": { "conference_name": null, "date": "2026 Jun 22", "date_precision": "day", "issue": "6", "normalized_date": "2026-06-22", "pages": "768-773", "proceedings_title": null, "publisher": "", "title": "Precision chemistry", "volume": "4", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "Potent and Receptor-Selective Germination Inhibitor for Striga hermonthica.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The olfactory bulb (OB) serves as the first relay station that processes odor information. Within the OB, odor representations are dynamically modulated by reciprocal synapses between excitatory mitral and tufted (M/T) cells and local inhibitory interneurons. Among these interneurons, periglomerular cells (PGCs) are GABAergic neurons located in the glomerular layer that provide inhibitory inputs to M/T cells. Although their anatomical and molecular properties have been extensively characterized, the in vivo dynamics of PGCs during odor processing and learning remain poorly understood. To address this question, we performed in vivo two-photon calcium imaging of awake male mice to monitor the activity of individual PGCs during odor-associated tasks. PGCs exhibited robust and odor-specific responses that varied among individual odorants. Repeated passive odor exposure reduced the number of odor-responsive PGCs while preserving their odor selectivity. In contrast, active odor discrimination learning expanded the population of odor-responsive PGCs and enhanced response amplitude. Furthermore, discriminating highly similar odor mixtures recruited a broader ensemble of PGCs with lower selectivity, but this representation sharpened over training, resulting in fewer yet more selective PGCs. These findings demonstrate the experience-dependent features of PGCs and reveal their critical role in tuning olfactory processing. Our study provides fundamental insights into how inhibitory circuits regulate sensory representations underlying adaptive odor-guided behaviors.Significance Statement Periglomerular cells (PGCs) in the olfactory bulb (OB) are inhibitory interneurons that modulate odor representations and regulate output from the OB to higher brain regions. Using chronic two-photon calcium imaging, we found that repeated passive odor exposure gradually reduced PGC responses, whereas the active Go/No-go odor discrimination task enhanced odor responses specifically to reward-associated odors. Moreover, when odor pairs became more similar, the population of PGCs showing excitatory or inhibitory responses to Go odors expanded across days. These results indicate that PGCs exhibit learning-dependent plasticity, enhancing responses to reward-predictive odors and thereby contributing to improved odor discrimination and adaptive behavior for future rewards.", "classifications": [ { "id": "JPMJCR1921", "label": "JPMJCR1921", "researcher": "Itaru Imayoshi", "type": "grant" }, { "id": "Imayoshi", "label": "Group Imayoshi", "parent": "Imayoshi", "type": "group" }, { "id": "Imayoshi", "label": "Team Imayoshi", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Akiko", "last_name": "Ide", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Itaru", "last_name": "Imayoshi", "name": null }, { "creator_type": "author", "first_name": "Masayuki", "last_name": "Sakamoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1523/eneuro.0171-26.2026" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "42331624" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Calcium", "descriptor_ui": "D002118", "major_topic": false }, { "descriptor": "Discrimination Learning", "descriptor_ui": "D004193", "major_topic": true }, { "descriptor": "GABAergic Neurons", "descriptor_ui": "D059330", "major_topic": true }, { "descriptor": "Interneurons", "descriptor_ui": "D007395", "major_topic": true }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Transgenic", "descriptor_ui": "D008822", "major_topic": false }, { "descriptor": "Neuronal Plasticity", "descriptor_ui": "D009473", "major_topic": true }, { "descriptor": "Odorants", "descriptor_ui": "D009812", "major_topic": false }, { "descriptor": "Olfactory Bulb", "descriptor_ui": "D009830", "major_topic": true }, { "descriptor": "Olfactory Perception", "descriptor_ui": "D055696", "major_topic": true }, { "descriptor": "Smell", "descriptor_ui": "D012903", "major_topic": false } ], "publication": { "conference_name": null, "date": "2026 Jun 22", "date_precision": "day", "issue": "", "normalized_date": "2026-06-22", "pages": "ENEURO.0171-26.2026", "proceedings_title": null, "publisher": "", "title": "eNeuro", "volume": "", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "Experience-dependent plasticity of periglomerular cells in the olfactory bulb.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "OBJECTIVE: Statins (HMG-CoA reductase inhibitors) are associated with myopathy, yet the precise in vivo mechanisms underlying this association remain unclear. Emerging evidence implicates a deficiency of geranylgeranyl pyrophosphate (GGPP), a key downstream isoprenoid metabolite of the mevalonate pathway. We employed novel muscle-specific genetic mouse models to elucidate the roles of GGPP and Rab geranylgeranyl transferase beta (RabGGT-beta) in the development of myopathy. METHODS: Using doxycycline-inducible Cre-LoxP technology, we generated three skeletal muscle-specific knockout (KO) models: Hmgcr-DimKO, Rabggtb-DimKO, and combined Hmgcr/Rabggtb-DimKO mice. The severity of myopathy was evaluated based on serum creatine kinase levels and histological examination. Mitochondrial mass and function were rigorously quantified. Prenylation deficit in Rabggtb-DimKO mice was confirmed via subcellular fractionation. To validate GGPP's involvement, rescue experiments were conducted using its precursor, geranylgeraniol (GGOH). RESULTS: Hmgcr KO resulted in pronounced myopathy, marked by an early reduction in mitochondria-rich myosin heavy chain (MyHC) type I and IIa muscle fibers, followed by a later reduction in mitochondria-poor glycolytic MyHC type IIb muscle fibers, and these changes were reversed by GGOH administration. Rabggtb-DimKO mice developed myopathy later than Hmgcr-DimKO mice; however, in Hmgcr/Rabggtb-DimKO mice, myopathy was dramatically accelerated and more severe. Across all models, mitochondrial dysfunction emerged early-preceding clinical signs of myopathy-consistent with a causal relationship. CONCLUSION: Our findings demonstrate that myopathy induced by HMGCR deficiency is primarily driven by GGPP depletion in a mouse model. Furthermore, impaired RabGGT-beta-mediated protein geranylgeranylation represents a critical downstream mechanism that aggravates the myopathic phenotype. Early mitochondrial abnormalities may contribute to the pathogenesis of myopathy due to disruption of the mevalonate pathway.", "classifications": [ { "id": "Miyamoto", "label": "Group Miyamoto", "parent": "Wakamoto", "type": "group" }, { "id": "Wakamoto", "label": "Team Wakamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yoshinori", "last_name": "Osaki", "name": null }, { "creator_type": "author", "first_name": "Yuhei", "last_name": "Mizunoe", "name": null }, { "creator_type": "author", "first_name": "Yoshimi", "last_name": "Nakagawa", "name": null }, { "creator_type": "author", "first_name": "Takafumi", "last_name": "Miyamoto", "name": null }, { "creator_type": "author", "first_name": "Ryo", "last_name": "Fujita", "name": null }, { "creator_type": "author", "first_name": "Song-Iee", "last_name": "Han", "name": null }, { "creator_type": "author", "first_name": "Masaya", "last_name": "Araki", "name": null }, { "creator_type": "author", "first_name": "Masataka", "last_name": "Tomoda", "name": null }, { "creator_type": "author", "first_name": "Kenta", "last_name": "Kainoh", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Ohno", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Iwasaki", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Matsuzaka", "name": null }, { "creator_type": "author", "first_name": "Hirohito", "last_name": "Sone", "name": null }, { "creator_type": "author", "first_name": "Ken", "last_name": "Ohashi", "name": null }, { "creator_type": "author", "first_name": "Shun", "last_name": "Ishibashi", "name": null }, { "creator_type": "author", "first_name": "Motohiro", "last_name": "Sekiya", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Shimano", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.molmet.2026.102406" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "42323079" } }, "mesh": [ { "descriptor": "Alkyl and Aryl Transferases", "descriptor_ui": "D019883", "major_topic": true }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Disease Models, Animal", "descriptor_ui": "D004195", "major_topic": false }, { "descriptor": "Hydroxymethylglutaryl CoA Reductases", "descriptor_ui": "D006903", "major_topic": true }, { "descriptor": "Hydroxymethylglutaryl-CoA Reductase Inhibitors", "descriptor_ui": "D019161", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Muscle, Skeletal", "descriptor_ui": "D018482", "major_topic": true }, { "descriptor": "Muscular Diseases", "descriptor_ui": "D009135", "major_topic": true }, { "descriptor": "Polyisoprenyl Phosphates", "descriptor_ui": "D011106", "major_topic": false }, { "descriptor": "Transferases", "descriptor_ui": "D014166", "major_topic": false } ], "publication": { "conference_name": null, "date": "2026 Jun 20", "date_precision": "day", "issue": "", "normalized_date": "2026-06-20", "pages": "102406", "proceedings_title": null, "publisher": "", "title": "Molecular metabolism", "volume": "", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "Skeletal muscle-specific deficiency of Rab geranylgeranyl transferase beta subunit induces myopathy and exacerbates the symptoms caused by HMG-CoA reductase deficiency in mice.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Disruption of mitochondrial morphology occurs during various diseases, but the biological significance is not entirely clear. Here, we describe a detailed step-by-step protocol for a chemically inducible dimerization (CID) system-based synthetic protein device, termed inducible counter mitochondrial morphology (iCMM). This system allows artificial manipulation of mitochondrial morphology on a timescale of minutes in living mammalian cells. We also describe an AI-assisted image processing approach. For complete details on the use and execution of this protocol, please refer to Miyamoto et al.(1) This protocol provides an updated version of the method described by Miyamoto et al.(2).", "classifications": [ { "id": "Miyamoto", "label": "Group Miyamoto", "parent": "Wakamoto", "type": "group" }, { "id": "Wakamoto", "label": "Team Wakamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Mayuko", "last_name": "Kano", "name": null }, { "creator_type": "author", "first_name": "Naoko", "last_name": "Onodera", "name": null }, { "creator_type": "author", "first_name": "Tomoto", "last_name": "Ura", "name": null }, { "creator_type": "author", "first_name": "Satone", "last_name": "Tanigaki", "name": null }, { "creator_type": "author", "first_name": "Teppei", "last_name": "Nishino", "name": null }, { "creator_type": "author", "first_name": "Takafumi", "last_name": "Miyamoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.xpro.2026.104635" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "42301815" } }, "mesh": [], "publication": { "conference_name": null, "date": "2026 Jun 16", "date_precision": "day", "issue": "3", "normalized_date": "2026-06-16", "pages": "104635", "proceedings_title": null, "publisher": "", "title": "STAR protocols", "volume": "7", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "Protocol update to: Protocol for rapid manipulation of mitochondrial morphology in living cells using inducible counter mitochondrial morphology.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Polatuzumab vedotin (PV), a CD79B-directed antibody-drug conjugate, is approved for treating diffuse large B-cell lymphoma (DLBCL). However, the clinical relevance of CD79B expression and the frequency of loss or decrease after PV-containing therapy remain unclear. We evaluated immunohistochemical CD79B expression using H-score (0-300) in 91 patients with DLBCL before PV-containing therapy and assessed post-treatment changes. Low CD79B expression was observed in 15 (16%) patients, including one case with no expression. Relapsed/refractory (R/R) DLBCL occurred more frequently in cases transformed from low-grade B-cell lymphoma than in de novo DLBCL (23% vs. 2%, P = 0.009), as well as in CD10-positive (25% vs. 49%, P = 0.033) and MUM1-negative (71% vs. 46%, P = 0.028) cases. R/R DLBCL also tended to occur more frequently in CD20-negative DLBCL than CD20-positive DLBCL (2% vs. 13%, P = 0.099). CD79B expression level was not associated with R/R DLBCL incidence. Among 15 patients with DLBCL with low CD79B expression, 60% achieved and maintained complete response after PV-containing therapy. Among 24 patients with recurrent tumor biopsies, 13% showed loss of/decreased CD79B expression. In conclusion, immunohistochemical CD79B expression was not significantly associated with PV-containing therapy efficacy, which remained effective even in DLBCL with low CD79B expression.", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yuto", "last_name": "Kaimi", "name": null }, { "creator_type": "author", "first_name": "Yuka", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Mai", "last_name": "Takeuchi", "name": null }, { "creator_type": "author", "first_name": "Yuta", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Shinichi", "last_name": "Makita", "name": null }, { "creator_type": "author", "first_name": "Noriko", "last_name": "Iwaki", "name": null }, { "creator_type": "author", "first_name": "Suguru", "last_name": "Fukuhara", "name": null }, { "creator_type": "author", "first_name": "Wataru", "last_name": "Munakata", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Izutsu", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null }, { "creator_type": "author", "first_name": "Akiko Miyagi", "last_name": "Maeshima", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/s00428-026-04619-7" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "42301308" } }, "mesh": [], "publication": { "conference_name": null, "date": "2026 Jun 16", "date_precision": "day", "issue": "", "normalized_date": "2026-06-16", "pages": "", "proceedings_title": null, "publisher": "", "title": "Virchows Archiv : an international journal of pathology", "volume": "", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "Association between CD79B expression and polatuzumab vedotin efficacy, and therapy-induced changes in CD79B expression in diffuse large B-cell lymphoma.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Peripherin (PRPH) is a class III intermediate filament protein expressed in peripheral nerves and upregulated during axon outgrowth and regeneration. In this study, we developed a transgenic Xenopus laevis line for long-term in vivo visualization of the peripheral nervous system. Deletion and motif analyses identified cis-regulatory regions within the promoter and intron 1, which are important for the neuronal expression of the X. laevis prph gene. Stable lines exhibited robust enhanced GFP reporter activity in developing neural primordia in embryos and in the peripheral nerves of tadpoles. Transgenic tadpoles enabled in vivo imaging of peripheral nerves throughout limb development. During larval limb regeneration, we observed modest early nerve entry into the blastema, recapitulating that seen in early limb development. In contrast, post-metamorphic limb blastemas displayed extensive innervation from the early phase of regeneration. Moreover, increased reporter activity in the nerves of the regenerating adult forelimb suggests regeneration-associated regulation of peripheral innervation and its potential role in blastema formation. This transgenic line will serve as a versatile tool for analyzing such large-scale neural remodeling across development, metamorphosis, and regeneration.", "classifications": [ { "id": "JPMJCR2025", "label": "JPMJCR2025", "researcher": "Yoshihiro Morishita", "type": "grant" }, { "id": "Morishita", "label": "Group Morishita", "parent": "Morishita", "type": "group" }, { "id": "Suzuki", "label": "Group Suzuki", "parent": "Morishita", "type": "group" }, { "id": "Morishita", "label": "Team Morishita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Miyuki", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Yosuke", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Rima", "last_name": "Mizuno", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Yajima", "name": null }, { "creator_type": "author", "first_name": "Shinichirou", "last_name": "Miura", "name": null }, { "creator_type": "author", "first_name": "Tetsuya", "last_name": "Endo", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Mochii", "name": null }, { "creator_type": "author", "first_name": "Ken-Ichi T.", "last_name": "Suzuki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1242/bio.062651" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "42145051" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Animals, Genetically Modified", "descriptor_ui": "D030801", "major_topic": false }, { "descriptor": "Extremities", "descriptor_ui": "D005121", "major_topic": true }, { "descriptor": "Gene Expression Regulation, Developmental", "descriptor_ui": "D018507", "major_topic": false }, { "descriptor": "Genes, Reporter", "descriptor_ui": "D017930", "major_topic": true }, { "descriptor": "Peripheral Nerves", "descriptor_ui": "D010525", "major_topic": true }, { "descriptor": "Peripherins", "descriptor_ui": "D064531", "major_topic": true }, { "descriptor": "Regeneration", "descriptor_ui": "D012038", "major_topic": true }, { "descriptor": "Xenopus laevis", "descriptor_ui": "D014982", "major_topic": true } ], "publication": { "conference_name": null, "date": "2026 Jun 15", "date_precision": "day", "issue": "6", "normalized_date": "2026-06-15", "pages": "bio062651", "proceedings_title": null, "publisher": "", "title": "Biology open", "volume": "15", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "Visualization of peripheral nerves in developing and regenerating limbs using a novel peripherin reporter line of Xenopus laevis.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "To date, there is no reliable and valid screening tool for paraphilic disorders (PDs) based on the diagnostic criteria of the International Classification of Diseases (ICD-11). The present study aimed to develop and cross-culturally examine the cross-cultural applicability of a new screening tool for PDs following the ICD-11 guidelines. METHODS: Top-down item development was conducted with expert practitioners in the field. Data were collected in 26 languages across 42 countries (N = 82,243; 39.5% men; 57.0% women; 3.4% gender-diverse; M(age) = 32.39 years, SD = 12.52). Cut-off scores were established per ICD-11 guidelines, and at-risk groups were compared with low-risk groups along theoretically relevant correlates (e.g., depression, anxiety). OUTCOMES: The Paraphilic Disorders Short Screen (PDSS) assesses seven paraphilias via 21 items. RESULTS: Voyeurism was most common paraphilic interest (PI) (19.42% of the total sample; n = 15,970), which also had the highest number of participants meeting the ICD-11 diagnostic cut-off (3.24%; n = 2,662). PI and PD groups consistently demonstrated more severe depression and anxiety symptoms than others. CONCLUSION: The PDSS is a reliable and valid screening tool that follows the latest ICD-11 guidelines; therefore, it has the capacity to enhance clinical practice and research by identifying individuals at risk.", "classifications": [ { "id": "Fujiwara", "label": "Group Fujiwara", "parent": "Fujiwara", "type": "group" }, { "id": "Fujiwara", "label": "Team Fujiwara", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Monika", "last_name": "Koos", "name": null }, { "creator_type": "author", "first_name": "Lena", "last_name": "Nagy", "name": null }, { "creator_type": "author", "first_name": "Shane W.", "last_name": "Kraus", "name": null }, { "creator_type": "author", "first_name": "Marc N.", "last_name": "Potenza", "name": null }, { "creator_type": "author", "first_name": "Zsolt", "last_name": "Demetrovics", "name": null }, { "creator_type": "author", "first_name": "Johannes", "last_name": "Fuss", "name": null }, { "creator_type": "author", "first_name": "Verena", "last_name": "Klein", "name": null }, { "creator_type": "author", "first_name": "Yen-Ling", "last_name": "Chen", "name": null }, { "creator_type": "author", "first_name": "Rafael", "last_name": "Ballester-Arnal", "name": null }, { "creator_type": "author", "first_name": "Dominik", "last_name": "Batthyany", "name": null }, { "creator_type": "author", "first_name": "Sophie", "last_name": "Bergeron", "name": null }, { "creator_type": "author", "first_name": "Joel", "last_name": "Billieux", "name": null }, { "creator_type": "author", "first_name": "Peer", "last_name": "Briken", "name": null }, { "creator_type": "author", "first_name": "Julius", "last_name": "Burkauskas", "name": null }, { "creator_type": "author", "first_name": "Georgina", "last_name": "Cardenas-Lopez", "name": null }, { "creator_type": "author", "first_name": "Joana", "last_name": "Carvalho", "name": null }, { "creator_type": "author", "first_name": "Jesus", "last_name": "Castro-Calvo", "name": null }, { "creator_type": "author", "first_name": "Lijun", "last_name": "Chen", "name": null }, { "creator_type": "author", "first_name": "Giacomo", "last_name": "Ciocca", "name": null }, { "creator_type": "author", "first_name": "Ornella", "last_name": "Corazza", "name": null }, { "creator_type": "author", "first_name": "Rita I.", "last_name": "Csako", "name": null }, { "creator_type": "author", "first_name": "David P.", "last_name": "Fernandez", "name": null }, { "creator_type": "author", "first_name": "Elaine F.", "last_name": "Fernandez", "name": null }, { "creator_type": "author", "first_name": "Hironobu", "last_name": "Fujiwara", "name": null }, { "creator_type": "author", "first_name": "Roman", "last_name": "Gabrhelik", "name": null }, { "creator_type": "author", "first_name": "Ateret", "last_name": "Gewirtz-Meydan", "name": null }, { "creator_type": "author", "first_name": "Biljana", "last_name": "Gjoneska", "name": null }, { "creator_type": "author", "first_name": "Mateusz", "last_name": "Gola", "name": null }, { "creator_type": "author", "first_name": "Joshua B.", "last_name": "Grubbs", "name": null }, { "creator_type": "author", "first_name": "Hashim T.", "last_name": "Hashim", "name": null }, { "creator_type": "author", "first_name": "Md Saiful", "last_name": "Islam", "name": null }, { "creator_type": "author", "first_name": "Mustafa", "last_name": "Ismail", "name": null }, { "creator_type": "author", "first_name": "Martha C.", "last_name": "Jimenez-Martinez", "name": null }, { "creator_type": "author", "first_name": "Tanja", "last_name": "Jurin", "name": null }, { "creator_type": "author", "first_name": "Ondrej", "last_name": "Kalina", "name": null }, { "creator_type": "author", "first_name": "Andras", "last_name": "Kolto", "name": null }, { "creator_type": "author", "first_name": "Chih-Ting", "last_name": "Lee", "name": null }, { "creator_type": "author", "first_name": "Sang-Kyu", "last_name": "Lee", "name": null }, { "creator_type": "author", "first_name": "Karol", "last_name": "Lewczuk", "name": null }, { "creator_type": "author", "first_name": "Chung-Ying", "last_name": "Lin", "name": null }, { "creator_type": "author", "first_name": "Christine", "last_name": "Lochner", "name": null }, { "creator_type": "author", "first_name": "Silvia", "last_name": "Lopez-Alvarado", "name": null }, { "creator_type": "author", "first_name": "Katerina", "last_name": "Lukavska", "name": null }, { "creator_type": "author", "first_name": "Percy", "last_name": "Mayta-Tristan", "name": null }, { "creator_type": "author", "first_name": "Dan J.", "last_name": "Miller", "name": null }, { "creator_type": "author", "first_name": "Olga", "last_name": "Orosova", "name": null }, { "creator_type": "author", "first_name": "Gabor", "last_name": "Orosz", "name": null }, { "creator_type": "author", "first_name": "Fernando P.", "last_name": "Ponce", "name": null }, { "creator_type": "author", "first_name": "Gonzalo R.", "last_name": "Quintana", "name": null }, { "creator_type": "author", "first_name": "Gabriel C.", "last_name": "Quintero Garzola", "name": null }, { "creator_type": "author", "first_name": "Jano", "last_name": "Ramos-Diaz", "name": null }, { "creator_type": "author", "first_name": "Kevin", "last_name": "Rigaud", "name": null }, { "creator_type": "author", "first_name": "Ann", "last_name": "Rousseau", "name": null }, { "creator_type": "author", "first_name": "Marco De Tubino", "last_name": "Scanavino", "name": null }, { "creator_type": "author", "first_name": "Marion K.", "last_name": "Schulmeyer", "name": null }, { "creator_type": "author", "first_name": "Pratap", "last_name": "Sharan", "name": null }, { "creator_type": "author", "first_name": "Mami", "last_name": "Shibata", "name": null }, { "creator_type": "author", "first_name": "Sheikh", "last_name": "Shoib", "name": null }, { "creator_type": "author", "first_name": "Vera", "last_name": "Sigre-Leiros", "name": null }, { "creator_type": "author", "first_name": "Luke", "last_name": "Sniewski", "name": null }, { "creator_type": "author", "first_name": "Ognen", "last_name": "Spasovski", "name": null }, { "creator_type": "author", "first_name": "Vesta", "last_name": "Steibliene", "name": null }, { "creator_type": "author", "first_name": "Dan J.", "last_name": "Stein", "name": null }, { "creator_type": "author", "first_name": "Julian", "last_name": "Strizek", "name": null }, { "creator_type": "author", "first_name": "Banu C.", "last_name": "Unsal", "name": null }, { "creator_type": "author", "first_name": "Marie-Pier", "last_name": "Vaillancourt-Morel", "name": null }, { "creator_type": "author", "first_name": "Marie Claire", "last_name": "Van Hout", "name": null }, { "creator_type": "author", "first_name": "Beata", "last_name": "Bothe", "name": null } ], "identifiers": { "doi": { "normalized": "10.1177/10790632261438676" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "42295117" } }, "mesh": [ { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Cross-Cultural Comparison", "descriptor_ui": "D003431", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "International Classification of Diseases", "descriptor_ui": "D038801", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mass Screening", "descriptor_ui": "D008403", "major_topic": true }, { "descriptor": "Paraphilic Disorders", "descriptor_ui": "D010262", "major_topic": true }, { "descriptor": "Psychometrics", "descriptor_ui": "D011594", "major_topic": false }, { "descriptor": "Reproducibility of Results", "descriptor_ui": "D015203", "major_topic": false }, { "descriptor": "Surveys and Questionnaires", "descriptor_ui": "D011795", "major_topic": false } ], "publication": { "conference_name": null, "date": "2026 Jun 15", "date_precision": "day", "issue": "", "normalized_date": "2026-06-15", "pages": "10790632261438676", "proceedings_title": null, "publisher": "", "title": "Sexual abuse : a journal of research and treatment", "volume": "", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "The Development of the Paraphilic Disorders Short Screen (PDSS) and Its Examination in Diverse Populations: A Large, Multi-Nation Study.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "During morphogenesis, cell divisions are precisely regulated in space and time. The biological objectives achieved by such regulation are not fully understood. Here, by applying a newly developed lineage-reconstruction pipeline to Drosophila pupal wing, we reveal that the wing is composed of distinct cell groups that differ in division number, timing, and spatial positioning relative to wing veins. We show that the frequencies of these lineages, together with their initial cell sizes and growth profiles, converge to achieve a highly conserved average cell size. Our data further suggest that distance from veins provides spatial information that biases where distinct lineages arise, and that loss of veins caused by perturbation of EGFR signaling suppresses a specific lineage and disrupts cell-size control. Finally, our results point to a multiscale organization of division patterns, in which vein-associated spatial information is integrated with local neighbor effects in a manner that would mitigate mechanical instability within the tissue. Together, these findings delineate a cell-size control mechanism based on coordinated divisions of distinct cell groups that supports robust morphogenesis and functional tissue design.", "classifications": [ { "id": "JPMJCR1923", "label": "JPMJCR1923", "researcher": "Satoshi Sawai", "type": "grant" }, { "id": "Ishihara", "label": "Group Ishihara", "parent": "Sawai", "type": "group" }, { "id": "Sawai", "label": "Group Sawai", "parent": "Sawai", "type": "group" }, { "id": "Sawai", "label": "Team Sawai", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Kaoru", "last_name": "Sugimura", "name": null }, { "creator_type": "author", "first_name": "Ryu", "last_name": "Takayanagi", "name": null }, { "creator_type": "author", "first_name": "Toshinori", "last_name": "Namba", "name": null }, { "creator_type": "author", "first_name": "Zeping", "last_name": "Qu", "name": null }, { "creator_type": "author", "first_name": "Shuji", "last_name": "Ishihara", "name": null } ], "identifiers": { "doi": { "normalized": "10.1242/dev.205474" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "42374939" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Division", "descriptor_ui": "D002455", "major_topic": true }, { "descriptor": "Cell Lineage", "descriptor_ui": "D019070", "major_topic": false }, { "descriptor": "Cell Size", "descriptor_ui": "D048429", "major_topic": true }, { "descriptor": "Drosophila", "descriptor_ui": "D004330", "major_topic": true }, { "descriptor": "Drosophila melanogaster", "descriptor_ui": "D004331", "major_topic": true }, { "descriptor": "Drosophila Proteins", "descriptor_ui": "D029721", "major_topic": false }, { "descriptor": "ErbB Receptors", "descriptor_ui": "D066246", "major_topic": false }, { "descriptor": "Morphogenesis", "descriptor_ui": "D009024", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Veins", "descriptor_ui": "D014680", "major_topic": true }, { "descriptor": "Wings, Animal", "descriptor_ui": "D014921", "major_topic": true } ], "publication": { "conference_name": null, "date": "2026 Jun 15", "date_precision": "day", "issue": "12", "normalized_date": "2026-06-15", "pages": "dev205474", "proceedings_title": null, "publisher": "", "title": "Development (Cambridge, England)", "volume": "153", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "Cell size control emerges from the vein-dependent coordinated divisions of distinct cell groups in Drosophila wing.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "", "classifications": [ { "id": "Onami", "label": "Group Onami", "parent": "Fujiwara", "type": "group" }, { "id": "Fujiwara", "label": "Team Fujiwara", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Sean L.", "last_name": "Meharry", "name": null }, { "creator_type": "author", "first_name": "Antoine", "last_name": "Borensztejn", "name": null }, { "creator_type": "author", "first_name": "Nathalie", "last_name": "Gaudreault", "name": null }, { "creator_type": "author", "first_name": "Jordan", "last_name": "Lucas", "name": null }, { "creator_type": "author", "first_name": "Gabe", "last_name": "Medrash", "name": null }, { "creator_type": "author", "first_name": "Lisa", "last_name": "Schaefbauer", "name": null }, { "creator_type": "author", "first_name": "Daniel", "last_name": "Toloudis", "name": null }, { "creator_type": "author", "first_name": "Anya", "last_name": "Wallace", "name": null }, { "creator_type": "author", "first_name": "Brian", "last_name": "Whitney", "name": null }, { "creator_type": "author", "first_name": "Lyndsay", "last_name": "Wilhelm", "name": null }, { "creator_type": "author", "first_name": "Yoav", "last_name": "Ben-Simon", "name": null }, { "creator_type": "author", "first_name": "Jean-Marie", "last_name": "Burel", "name": null }, { "creator_type": "author", "first_name": "Jianxu", "last_name": "Chen", "name": null }, { "creator_type": "author", "first_name": "Kevin W.", "last_name": "Eliceiri", "name": null }, { "creator_type": "author", "first_name": "Anika", "last_name": "Gruneboom", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Kyoda", "name": null }, { "creator_type": "author", "first_name": "Josh", "last_name": "Moore", "name": null }, { "creator_type": "author", "first_name": "William", "last_name": "Moore", "name": null }, { "creator_type": "author", "first_name": "Shuichi", "last_name": "Onami", "name": null }, { "creator_type": "author", "first_name": "Davide", "last_name": "Panzeri", "name": null }, { "creator_type": "author", "first_name": "Curtis T.", "last_name": "Rueden", "name": null }, { "creator_type": "author", "first_name": "Bosiljka", "last_name": "Tasic", "name": null }, { "creator_type": "author", "first_name": "Graham T.", "last_name": "Johnson", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41592-026-03130-w" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "42298069" } }, "mesh": [], "publication": { "conference_name": null, "date": "2026 Jun 15", "date_precision": "day", "issue": "", "normalized_date": "2026-06-15", "pages": "", "proceedings_title": null, "publisher": "", "title": "Nature methods", "volume": "", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "Search, organize, aggregate and share image data with BioFile Finder (BFF).", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Elongation of flowering stems is crucial for successful sexual reproduction and seed dispersal, yet its cellular mechanisms remain largely unknown. Traditionally, it has been assumed that new cells supplied by meristematic tissues sustain stem growth. However, our stem growth and cell proliferation assays revealed that active cell division also occurred in differentiated cells below the rib zone. Given the essential role of gibberellin (GA) in promoting stem elongation, we compared cell growth between wild-type and GA-deficient mutant plants. In the upper 0.0-1.0 cm of the stem, GA-deficient mutants showed reduced cell proliferation and unexpectedly enlarged cells, despite the well-known role of GA in cell expansion. This finding implies that cell proliferation is the primary driver of GA-dependent stem elongation. To investigate how GA biosynthesis is regulated during stem growth, we conducted phytohormone and gene expression assays using juvenile seedlings, dissected shoot apices, and stems. The data suggested that the production of bioactive GA4 was upregulated in the upper stem through the induction of the GA-biosynthetic gene GIBBERELLIN 20 OXIDASE 1 and its spatial coexpression with the downstream gene GIBBERELLIN 3 OXIDASE 1. Our results provide detailed insight into GA-dependent inflorescence stem elongation, with implications for other eudicots, including crop species.", "classifications": [ { "id": "Sato", "label": "Group Sato", "parent": "Tsuchiya", "type": "group" }, { "id": "Tsuchiya", "label": "Team Tsuchiya", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Mio", "last_name": "Mizushima", "name": null }, { "creator_type": "author", "first_name": "Kosuke", "last_name": "Matsumoto", "name": null }, { "creator_type": "author", "first_name": "Mikiko", "last_name": "Kojima", "name": null }, { "creator_type": "author", "first_name": "Yumiko", "last_name": "Takebayashi", "name": null }, { "creator_type": "author", "first_name": "Ken-Ichi", "last_name": "Kurotani", "name": null }, { "creator_type": "author", "first_name": "Miya", "last_name": "Mizutani", "name": null }, { "creator_type": "author", "first_name": "Xiaosa", "last_name": "Xu", "name": null }, { "creator_type": "author", "first_name": "Yoshikatsu", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Jutarou", "last_name": "Fukazawa", "name": null }, { "creator_type": "author", "first_name": "Naoyuki", "last_name": "Uchida", "name": null }, { "creator_type": "author", "first_name": "Keisuke", "last_name": "Nagai", "name": null }, { "creator_type": "author", "first_name": "Atushi J.", "last_name": "Nagano", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Sakakibara", "name": null }, { "creator_type": "author", "first_name": "Motoyuki", "last_name": "Ashikari", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Takagi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1093/pcp/pcag077" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "42287152" } }, "mesh": [], "publication": { "conference_name": null, "date": "2026 Jun 13", "date_precision": "day", "issue": "", "normalized_date": "2026-06-13", "pages": "pcag077", "proceedings_title": null, "publisher": "", "title": "Plant & cell physiology", "volume": "", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "GA20ox1-mediated GA4 production promotes inflorescence stem growth in Arabidopsis via inner-layer cell proliferation.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND AND AIMS: Social media increasingly shapes body image by promoting often unattainable beauty ideals. Concurrently, targeted online marketing of image- and performance-enhancing drugs (IPEDs) exploits these vulnerabilities, intensifying anxiety and fostering maladaptive behaviours such as problematic usage of the internet (PUI), compulsive exercise, and IPEDs consumption. This study explores these behaviours across nine countries and examines how PUI, excessive exercise, and IPEDs use predict appearance anxiety, aiming to inform targeted prevention strategies for at-risk populations. METHODS: A total of 3,514 participants from nine countries completed a web-based survey assessing sociodemographic data, appearance anxiety (AAI), problematic internet use (PIUQ-9), excessive exercise (EAI-R), and IPEDs intake. RESULTS: Appearance-related anxiety was observed in 12% of the participants, with the highest prevalence in Mexico (20.7%), Japan (13.8%) and Italy (13.6%). Median PUI scores were highest in Mexico (22.57) and Singapore (21.59). Excessive exercise was reported by 3.6% with no significant country differences. IPEDs use was reported by 28.3% of the sample, with the highest rates in Japan (60.6%). Logistic regression analyses revealed that PUI, excessive exercise and IPEDs use were significant predictors of appearance-related anxiety. DISCUSSION AND CONCLUSIONS: The strong associations between PUI, excessive exercise, IPEDs use, and appearance anxiety underscore the complex interplay between online exposure, body image concerns and mental health. Cross-country differences suggest that socio-cultural factors influence appearance-related anxiety. These findings highlight the need for culturally sensitive interventions and policy measures that address the impact of digital media on body image, particularly to protect vulnerable populations.", "classifications": [ { "id": "Fujiwara", "label": "Group Fujiwara", "parent": "Fujiwara", "type": "group" }, { "id": "Fujiwara", "label": "Team Fujiwara", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Artemisa R.", "last_name": "Dores", "name": null }, { "creator_type": "author", "first_name": "Julius", "last_name": "Burkaukas", "name": null }, { "creator_type": "author", "first_name": "Agne", "last_name": "Stanyte", "name": null }, { "creator_type": "author", "first_name": "Aiste", "last_name": "Pranckeviciene", "name": null }, { "creator_type": "author", "first_name": "Irene P.", "last_name": "Carvalho", "name": null }, { "creator_type": "author", "first_name": "Thomas", "last_name": "Zandonai", "name": null }, { "creator_type": "author", "first_name": "Pierluigi", "last_name": "Simonato", "name": null }, { "creator_type": "author", "first_name": "Ilaria", "last_name": "De Luca", "name": null }, { "creator_type": "author", "first_name": "Alessandro", "last_name": "Carollo", "name": null }, { "creator_type": "author", "first_name": "Krisztina Edina", "last_name": "Abel", "name": null }, { "creator_type": "author", "first_name": "Attila", "last_name": "Szabo", "name": null }, { "creator_type": "author", "first_name": "Rita", "last_name": "Kovacsik", "name": null }, { "creator_type": "author", "first_name": "Hironobu", "last_name": "Fujiwara", "name": null }, { "creator_type": "author", "first_name": "Mami", "last_name": "Shibata", "name": null }, { "creator_type": "author", "first_name": "Andreea", "last_name": "Girleanu", "name": null }, { "creator_type": "author", "first_name": "Alejandra Rebeca", "last_name": "Melero Ventola", "name": null }, { "creator_type": "author", "first_name": "Ricardo M.", "last_name": "Santos-Labrador", "name": null }, { "creator_type": "author", "first_name": "Nelson", "last_name": "Bruno de Almeida Cunha", "name": null }, { "creator_type": "author", "first_name": "Gabriele", "last_name": "Penazzi", "name": null }, { "creator_type": "author", "first_name": "Sofia", "last_name": "Venturini", "name": null }, { "creator_type": "author", "first_name": "Fabio", "last_name": "Castro", "name": null }, { "creator_type": "author", "first_name": "Lambros", "last_name": "Lazuras", "name": null }, { "creator_type": "author", "first_name": "Gianluca", "last_name": "Esposito", "name": null }, { "creator_type": "author", "first_name": "Zsolt", "last_name": "Demetrovics", "name": null }, { "creator_type": "author", "first_name": "Ornella", "last_name": "Corazza", "name": null } ], "identifiers": { "doi": { "normalized": "10.1556/2006.2025.00317" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "42284098" } }, "mesh": [ { "descriptor": "Adolescent", "descriptor_ui": "D000293", "major_topic": false }, { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Anxiety", "descriptor_ui": "D001007", "major_topic": true }, { "descriptor": "Behavior, Addictive", "descriptor_ui": "D016739", "major_topic": true }, { "descriptor": "Body Image", "descriptor_ui": "D001828", "major_topic": true }, { "descriptor": "Cross-Cultural Comparison", "descriptor_ui": "D003431", "major_topic": false }, { "descriptor": "Digital Media", "descriptor_ui": "D000098624", "major_topic": false }, { "descriptor": "Exercise", "descriptor_ui": "D015444", "major_topic": true }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Internet", "descriptor_ui": "D020407", "major_topic": false }, { "descriptor": "Internet Addiction Disorder", "descriptor_ui": "D000082424", "major_topic": true }, { "descriptor": "Internet Use", "descriptor_ui": "D000084362", "major_topic": true }, { "descriptor": "Italy", "descriptor_ui": "D007558", "major_topic": false }, { "descriptor": "Japan", "descriptor_ui": "D007564", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Media Exposure", "descriptor_ui": "D000097822", "major_topic": false }, { "descriptor": "Mexico", "descriptor_ui": "D008800", "major_topic": false }, { "descriptor": "Performance-Enhancing Substances", "descriptor_ui": "D058573", "major_topic": true }, { "descriptor": "Prevalence", "descriptor_ui": "D015995", "major_topic": false }, { "descriptor": "Singapore", "descriptor_ui": "D012846", "major_topic": false }, { "descriptor": "Social Media", "descriptor_ui": "D061108", "major_topic": true }, { "descriptor": "Young Adult", "descriptor_ui": "D055815", "major_topic": false } ], "publication": { "conference_name": null, "date": "2026 Jun 12", "date_precision": "day", "issue": "", "normalized_date": "2026-06-12", "pages": "2006.2025.00317", "proceedings_title": null, "publisher": "", "title": "Journal of behavioral addictions", "volume": "", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "From social media to body image distress: Problematic internet use, exercise addiction, and enhancement drugs use across countries.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: Problematic Use of the Internet (PUI) has been associated with functional alterations in the default mode network (DMN), which contains critical hubs in the entire brain network. Previous studies have predicted that hub disruption leads to widespread network alterations; however, whether DMN functional connectivity mediates the relationship between PUI and global network topology remains unclear. This study examined whether DMN connectivity mediates PUI-related brain network topology. METHODS: Resting-state functional magnetic resonance imaging data were collected from 190 healthy participants aged 20-69 years. DMN functional connectivity was assessed using region of interest (ROI)-to-ROI analyses with the Generalized Problematic Internet Use Scale-2 (GPIUS-2) as the primary predictor, controlling for age, sex, and mean framewise displacement. Graph-theoretical analyses quantified whole-brain network properties, including the clustering coefficient (Cp), shortest path length (Lp), global efficiency (Eg), and local efficiency (Eloc). Mediation analyses were performed to determine whether DMN functional connectivity mediates the relationship between GPIUS-2 and each metric. RESULTS: The functional connectivity values of all 17 DMN cluster pairs showed negative partial correlations with PUI severity (p-FDR < 0.05). Mean DMN connectivity strongly predicted global network topology (|rho| = 0.36-0.41, all p-FDR < 1 x 10(-6)). Mediation analyses revealed that DMN functional connectivity substantially mediated the relationship between PUI severity and each metric (indirect effects: all p-FDR < 0.001; all direct effects p > 0.49). Reduced DMN connectivity was associated with decreased Cp and Eloc, increased Eg, and decreased Lp, indicating a deviation from optimal small-world organization. CONCLUSION: DMN hub connectivity serves as a critical neurobiological pathway through which the PUI influences the whole-brain network organization.", "classifications": [ { "id": "Fujiwara", "label": "Group Fujiwara", "parent": "Fujiwara", "type": "group" }, { "id": "Fujiwara", "label": "Team Fujiwara", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Nagara", "last_name": "Takao", "name": null }, { "creator_type": "author", "first_name": "Naoya", "last_name": "Oishi", "name": null }, { "creator_type": "author", "first_name": "Qi", "last_name": "Dai", "name": null }, { "creator_type": "author", "first_name": "Lichang", "last_name": "Yao", "name": null }, { "creator_type": "author", "first_name": "Sayaka", "last_name": "Yoshimura", "name": null }, { "creator_type": "author", "first_name": "Mami", "last_name": "Shibata", "name": null }, { "creator_type": "author", "first_name": "Morio", "last_name": "Aki", "name": null }, { "creator_type": "author", "first_name": "Saki", "last_name": "Akahori", "name": null }, { "creator_type": "author", "first_name": "Michael", "last_name": "Spantios", "name": null }, { "creator_type": "author", "first_name": "Toshiya", "last_name": "Murai", "name": null }, { "creator_type": "author", "first_name": "Hironobu", "last_name": "Fujiwara", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.comppsych.2026.152725" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "42296886" } }, "mesh": [ { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Brain", "descriptor_ui": "D001921", "major_topic": true }, { "descriptor": "Brain Mapping", "descriptor_ui": "D001931", "major_topic": false }, { "descriptor": "Default Mode Network", "descriptor_ui": "D000082702", "major_topic": true }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Internet", "descriptor_ui": "D020407", "major_topic": true }, { "descriptor": "Internet Addiction Disorder", "descriptor_ui": "D000082424", "major_topic": true }, { "descriptor": "Magnetic Resonance Imaging", "descriptor_ui": "D008279", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Nerve Net", "descriptor_ui": "D009415", "major_topic": true }, { "descriptor": "Neural Pathways", "descriptor_ui": "D009434", "major_topic": false }, { "descriptor": "Young Adult", "descriptor_ui": "D055815", "major_topic": false } ], "publication": { "conference_name": null, "date": "2026 Jun 11", "date_precision": "day", "issue": "", "normalized_date": "2026-06-11", "pages": "152725", "proceedings_title": null, "publisher": "", "title": "Comprehensive psychiatry", "volume": "149", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "Default mode network hub disruption links problematic use of the Internet to brain network disorganization.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "CDK12 and CDK13, two transcriptional cyclin-dependent kinases (CDKs), are emerging as therapeutic targets in epithelial cancers due to their vital roles in transcriptional elongation and maintaining genomic stability. However, the absence of predictive biomarkers may impede the clinical use of CDK12/13 inhibitors. Here, we identify CDK10 as a consistent and kinase-dependent regulator of sensitivity to CDK12/13 inhibition. A genome-wide CRISPR-Cas9 screen across six breast and ovarian cancer models reveals CDK10 loss as a top-ranked enhancer of response to the selective CDK12/13 inhibitor CTX-439. Functional validation in multiple cancer cell lines and xenograft models shows that CDK10 deficiency boosts apoptotic responses and increases the antitumor effects of CDK12/13 inhibition. Mechanistically, CDK10 loss extends the duration of CTX-439-induced transcriptional suppression and delays RNA polymerase II re-engagement at sensitive gene loci, exemplified by CAPN7 and SENP6. These findings indicate CDK10 as a probable biomarker for patient stratification and as a co-target to boost the efficacy of transcriptional therapies. Our work reveals a previously underappreciated role for CDK10 in transcriptional resilience, emphasizing its potential to guide and enhance CDK12/13-based cancer treatments.", "classifications": [ { "id": "Yusa", "label": "Group Yusa", "parent": "Eiraku", "type": "group" }, { "id": "Eiraku", "label": "Team Eiraku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Shafiqul", "last_name": "Islam", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Tarumoto", "name": null }, { "creator_type": "author", "first_name": "Mariko", "last_name": "Takano", "name": null }, { "creator_type": "author", "first_name": "Seiichi", "last_name": "Sugino", "name": null }, { "creator_type": "author", "first_name": "Gohei", "last_name": "Nishibuchi", "name": null }, { "creator_type": "author", "first_name": "Akio", "last_name": "Mizutani", "name": null }, { "creator_type": "author", "first_name": "Hiroko", "last_name": "Yamakawa", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Morishita", "name": null }, { "creator_type": "author", "first_name": "Kosuke", "last_name": "Yusa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41419-026-08973-x" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "42270604" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Apoptosis", "descriptor_ui": "D017209", "major_topic": false }, { "descriptor": "Breast Neoplasms", "descriptor_ui": "D001943", "major_topic": true }, { "descriptor": "CDC2 Protein Kinase", "descriptor_ui": "D016203", "major_topic": false }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Cyclin-Dependent Kinases", "descriptor_ui": "D018844", "major_topic": true }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Gene Expression Regulation, Neoplastic", "descriptor_ui": "D015972", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Protein Kinase Inhibitors", "descriptor_ui": "D047428", "major_topic": true }, { "descriptor": "RNA Polymerase II", "descriptor_ui": "D012319", "major_topic": false }, { "descriptor": "Transcription, Genetic", "descriptor_ui": "D014158", "major_topic": true }, { "descriptor": "Xenograft Model Antitumor Assays", "descriptor_ui": "D023041", "major_topic": false } ], "publication": { "conference_name": null, "date": "2026 Jun 11", "date_precision": "day", "issue": "", "normalized_date": "2026-06-11", "pages": "", "proceedings_title": null, "publisher": "", "title": "Cell death & disease", "volume": "", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "CDK10 loss primes tumor cells for transcriptional vulnerability and sensitizes to CDK12/13 inhibition.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "In the original publication [1], there was a mistake in relation to the cited references:8 [...].", "classifications": [ { "id": "Hamamoto", "label": "Group Hamamoto", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Reina", "last_name": "Komatsu", "name": null }, { "creator_type": "author", "first_name": "Masaaki", "last_name": "Komatsu", "name": null }, { "creator_type": "author", "first_name": "Katsuji", "last_name": "Takeda", "name": null }, { "creator_type": "author", "first_name": "Naoaki", "last_name": "Harada", "name": null }, { "creator_type": "author", "first_name": "Naoki", "last_name": "Teraya", "name": null }, { "creator_type": "author", "first_name": "Shohei", "last_name": "Wakisaka", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Natsume", "name": null }, { "creator_type": "author", "first_name": "Tomonori", "last_name": "Taniguchi", "name": null }, { "creator_type": "author", "first_name": "Rina", "last_name": "Aoyama", "name": null }, { "creator_type": "author", "first_name": "Mayumi", "last_name": "Kaneko", "name": null }, { "creator_type": "author", "first_name": "Kazuki", "last_name": "Iwamoto", "name": null }, { "creator_type": "author", "first_name": "Ryu", "last_name": "Matsuoka", "name": null }, { "creator_type": "author", "first_name": "Akihiko", "last_name": "Sekizawa", "name": null }, { "creator_type": "author", "first_name": "Ryuji", "last_name": "Hamamoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.3390/bioengineering13060672" }, "pmcid": { "normalized": "PMC13296249" }, "pmid": { "normalized": "42351958" } }, "mesh": [], "publication": { "conference_name": null, "date": "2026 Jun 10", "date_precision": "day", "issue": "6", "normalized_date": "2026-06-10", "pages": "", "proceedings_title": null, "publisher": "", "title": "Bioengineering (Basel, Switzerland)", "volume": "13", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "Correction: Komatsu et al. Three-Dimensional Visualization and Detection of the Pulmonary Venous-Left Atrium Connection Using Artificial Intelligence in Fetal Cardiac Ultrasound Screening. Bioengineering 2026, 13, 100.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Gastrointestinal stromal tumor (GIST) is the most common gastrointestinal mesenchymal tumor, driven by tyrosine-protein kinase (KIT) and platelet-derived growth factor receptor A (PDGFRA) mutations. Specific variants, such as KIT exon 11 deletions, carry prognostic and therapeutic implications, whereas wild-type (WT) variants derive limited benefit from tyrosine kinase inhibitors (TKIs). Given the limited reproducibility of established clinicopathological risk models, deep learning (DL) applied to whole-slide images (WSIs) emerged as a promising tool for molecular classification and prognostic assessment. We analyzed 8398 GIST cases from 21 centers in 7 countries, including 7238 with molecular data and 2638 with clinical follow-up. DL models were trained on WSIs to predict mutations, treatment sensitivity, and recurrence-free survival (RFS). DL predicted mutational status in GIST from WSIs, with area under the curve (AUC) of 0.87 for KIT and 0.96 for PDGFRA, and high performance was observed for subtypes, including KIT exon 11 del-inss 557-558 (0.67) and PDGFRA exon 18 D842V (0.93). For therapeutic categories, performance reached 0.84 for avapritinib sensitivity and 0.81 for imatinib sensitivity. DL models predicted RFS, with hazard-ratios (HR) of 8.44 in the overall cohort and 4.74 in patients receiving adjuvant therapy. Prognostic performance was comparable to pathology-based scores, with highest discrimination in the overall cohort and in patients without adjuvant therapy. DL applied to WSIs enables prediction of molecular alterations, treatment sensitivity, and RFS in GIST, performing comparably to established risk scores across international cohorts, providing a baseline for future multimodal predictors.", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Arianna", "last_name": "Bonetti", "name": null }, { "creator_type": "author", "first_name": "Van-Linh", "last_name": "Le", "name": null }, { "creator_type": "author", "first_name": "Zunamys I.", "last_name": "Carrero", "name": null }, { "creator_type": "author", "first_name": "Fabian", "last_name": "Wolf", "name": null }, { "creator_type": "author", "first_name": "Marco", "last_name": "Gustav", "name": null }, { "creator_type": "author", "first_name": "Suk Wai", "last_name": "Lam", "name": null }, { "creator_type": "author", "first_name": "Lucile", "last_name": "Vanhersecke", "name": null }, { "creator_type": "author", "first_name": "Pawel", "last_name": "Sobczuk", "name": null }, { "creator_type": "author", "first_name": "Francois", "last_name": "Le Loarer", "name": null }, { "creator_type": "author", "first_name": "Malgorzata", "last_name": "Lenarcik", "name": null }, { "creator_type": "author", "first_name": "Piotr", "last_name": "Rutkowski", "name": null }, { "creator_type": "author", "first_name": "Joris M.", "last_name": "van Sabben", "name": null }, { "creator_type": "author", "first_name": "Neeltje", "last_name": "Steeghs", "name": null }, { "creator_type": "author", "first_name": "Hester H.", "last_name": "Van Boven", "name": null }, { "creator_type": "author", "first_name": "Isidro", "last_name": "Machado", "name": null }, { "creator_type": "author", "first_name": "Silvia", "last_name": "Bague", "name": null }, { "creator_type": "author", "first_name": "Samuel", "last_name": "Navarro", "name": null }, { "creator_type": "author", "first_name": "Emilio", "last_name": "Medina-Ceballos", "name": null }, { "creator_type": "author", "first_name": "Carolina", "last_name": "Agra-Pujol", "name": null }, { "creator_type": "author", "first_name": "Francisco", "last_name": "Giner", "name": null }, { "creator_type": "author", "first_name": "Gustavo", "last_name": "TapiaPathology Department Hospital Univers", "name": null }, { "creator_type": "author", "first_name": "Alba", "last_name": "Hernandez-Gallego", "name": null }, { "creator_type": "author", "first_name": "Gema", "last_name": "Civantos-Jubera", "name": null }, { "creator_type": "author", "first_name": "Miriam", "last_name": "Cuatrecasas", "name": null }, { "creator_type": "author", "first_name": "Sandra", "last_name": "Lopez-Prades", "name": null }, { "creator_type": "author", "first_name": "Raul", "last_name": "Perret", "name": null }, { "creator_type": "author", "first_name": "Isabelle", "last_name": "Soubeyran", "name": null }, { "creator_type": "author", "first_name": "Emmanuel", "last_name": "Khalifa", "name": null }, { "creator_type": "author", "first_name": "Laura", "last_name": "Blouin", "name": null }, { "creator_type": "author", "first_name": "Eva", "last_name": "Wardelmann", "name": null }, { "creator_type": "author", "first_name": "Alexandra", "last_name": "Meurgey", "name": null }, { "creator_type": "author", "first_name": "Paola", "last_name": "Collini", "name": null }, { "creator_type": "author", "first_name": "Artem", "last_name": "Voloshin", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null }, { "creator_type": "author", "first_name": "Hidekazu", "last_name": "Hirano", "name": null }, { "creator_type": "author", "first_name": "Alessandro", "last_name": "Gronchi", "name": null }, { "creator_type": "author", "first_name": "Toshirou", "last_name": "Nishida", "name": null }, { "creator_type": "author", "first_name": "Olivier", "last_name": "Bouche", "name": null }, { "creator_type": "author", "first_name": "Jean-Francois", "last_name": "Emile", "name": null }, { "creator_type": "author", "first_name": "Carine", "last_name": "Ngo", "name": null }, { "creator_type": "author", "first_name": "Peter", "last_name": "Hohenberger", "name": null }, { "creator_type": "author", "first_name": "Cristina", "last_name": "Cotarelo", "name": null }, { "creator_type": "author", "first_name": "Jens", "last_name": "Jakob", "name": null }, { "creator_type": "author", "first_name": "Judith V. M. G.", "last_name": "Bovee", "name": null }, { "creator_type": "author", "first_name": "Hans", "last_name": "Gelderblom", "name": null }, { "creator_type": "author", "first_name": "Anna", "last_name": "Szumera-Cieckiewicz", "name": null }, { "creator_type": "author", "first_name": "Myriam", "last_name": "Jean-Denis", "name": null }, { "creator_type": "author", "first_name": "Julien", "last_name": "Bollard", "name": null }, { "creator_type": "author", "first_name": "Nathalie", "last_name": "Lassau", "name": null }, { "creator_type": "author", "first_name": "Axel", "last_name": "Le Cesne", "name": null }, { "creator_type": "author", "first_name": "Jean-Yves", "last_name": "Blay", "name": null }, { "creator_type": "author", "first_name": "Antoine", "last_name": "Italiano", "name": null }, { "creator_type": "author", "first_name": "Amandine", "last_name": "Crombe", "name": null }, { "creator_type": "author", "first_name": "Jean-Michel", "last_name": "Coindre", "name": null }, { "creator_type": "author", "first_name": "Jakob Nikolas", "last_name": "Kather", "name": null } ], "identifiers": { "doi": { "normalized": "10.1158/0008-5472.can-26-0132" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "42258704" } }, "mesh": [ { "descriptor": "Avapritinib", "descriptor_ui": "D000099289", "major_topic": false }, { "descriptor": "Deep Learning", "descriptor_ui": "D000077321", "major_topic": true }, { "descriptor": "Gastrointestinal Neoplasms", "descriptor_ui": "D005770", "major_topic": true }, { "descriptor": "Gastrointestinal Stromal Tumors", "descriptor_ui": "D046152", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Imatinib Mesylate", "descriptor_ui": "D000068877", "major_topic": false }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": true }, { "descriptor": "Predictive Learning Models", "descriptor_ui": "D000098412", "major_topic": false }, { "descriptor": "Prognosis", "descriptor_ui": "D011379", "major_topic": false }, { "descriptor": "Protein Kinase Inhibitors", "descriptor_ui": "D047428", "major_topic": false }, { "descriptor": "Proto-Oncogene Proteins c-kit", "descriptor_ui": "D019009", "major_topic": true }, { "descriptor": "Receptor, Platelet-Derived Growth Factor alpha", "descriptor_ui": "D020796", "major_topic": false } ], "publication": { "conference_name": null, "date": "2026 Jun 8", "date_precision": "day", "issue": "", "normalized_date": "2026-06-08", "pages": "", "proceedings_title": null, "publisher": "", "title": "Cancer research", "volume": "", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "Deep Learning Predicts Mutations and Outcomes in Gastrointestinal Stromal Tumors from Whole-Slide Images.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Proteins function not only through intramolecular folding and intermolecular complex formation but also through phase transitions driven by intermolecular interactions. Such phases, including liquid-like condensates, amorphous aggregates (AAs), and amyloid fibrils, are linked to distinct biological functions and pathologies. Although the transition from liquid-like condensates to amyloids has been extensively studied, the kinetic relationships between amyloids and other metastable solid states under cell-sized confinement remain unclear, which may hinder the establishment of effective therapeutic strategies. This knowledge gap arises because bulk-scale experiments inevitably lead to the conversion of metastable phases into the most stable phase. We developed a droplet-based microfluidic system that quantifies amyloid nucleation and metastable AA formation. Using the yeast prion protein Sup35, we found that condensates convert into both amyloids and AAs and that AA formation imposes a kinetic barrier that suppresses amyloid formation in a size-dependent manner at the micrometer scale, highlighting the importance of size effects in condensate-to-amyloid transitions. Furthermore, we demonstrated that the well-known amyloid inhibitor (-)-epigallocatechin-3-gallate paradoxically promoted amyloid formation at low concentrations by modulating the AA and amyloid nucleation kinetics. This phenomenon cannot, in principle, be observed in bulk-scale experiments and became apparent only under micrometer-scale confinement in the present system. These findings provide fundamental insights into protein phase transitions in cellular environments and may guide the development of novel therapeutic strategies targeting the metastable aggregates of amyloidogenic proteins.", "classifications": [ { "id": "Nakabayashi", "label": "Group Nakabayashi", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Junka", "last_name": "Kawakami", "name": null }, { "creator_type": "author", "first_name": "Taiki", "last_name": "Ozawa", "name": null }, { "creator_type": "author", "first_name": "Yoko", "last_name": "Maruyama", "name": null }, { "creator_type": "author", "first_name": "Honoka", "last_name": "Ishikawa", "name": null }, { "creator_type": "author", "first_name": "Yuto", "last_name": "Oshita", "name": null }, { "creator_type": "author", "first_name": "Kota", "last_name": "Yamauchi", "name": null }, { "creator_type": "author", "first_name": "Koichi", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Shinji", "last_name": "Kajimoto", "name": null }, { "creator_type": "author", "first_name": "Takakazu", "last_name": "Nakabayashi", "name": null }, { "creator_type": "author", "first_name": "Shunsuke", "last_name": "Tomita", "name": null }, { "creator_type": "author", "first_name": "Tanushree", "last_name": "Agarwal", "name": null }, { "creator_type": "author", "first_name": "Tomas", "last_name": "Sneideris", "name": null }, { "creator_type": "author", "first_name": "Kichitaro", "last_name": "Nakajima", "name": null }, { "creator_type": "author", "first_name": "Kentaro", "last_name": "Shiraki", "name": null }, { "creator_type": "author", "first_name": "Hideki", "last_name": "Taguchi", "name": null }, { "creator_type": "author", "first_name": "Akihide", "last_name": "Hibara", "name": null }, { "creator_type": "author", "first_name": "Tuomas", "last_name": "Knowles", "name": null }, { "creator_type": "author", "first_name": "Eri", "last_name": "Chatani", "name": null }, { "creator_type": "author", "first_name": "Yuta", "last_name": "Mizuno", "name": null }, { "creator_type": "author", "first_name": "Yumiko", "last_name": "Ohhashi", "name": null }, { "creator_type": "author", "first_name": "Mao", "last_name": "Fukuyama", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/jacs.6c02816" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "42249853" } }, "mesh": [ { "descriptor": "Amyloid", "descriptor_ui": "D000682", "major_topic": true }, { "descriptor": "Biomolecular Condensates", "descriptor_ui": "D000091582", "major_topic": true }, { "descriptor": "Catechin", "descriptor_ui": "D002392", "major_topic": false }, { "descriptor": "Kinetics", "descriptor_ui": "D007700", "major_topic": false }, { "descriptor": "Particle Size", "descriptor_ui": "D010316", "major_topic": false }, { "descriptor": "Peptide Termination Factors", "descriptor_ui": "D010454", "major_topic": true }, { "descriptor": "Phase Separation", "descriptor_ui": "D000095496", "major_topic": false }, { "descriptor": "Phase Transition", "descriptor_ui": "D044367", "major_topic": false }, { "descriptor": "Saccharomyces cerevisiae Proteins", "descriptor_ui": "D029701", "major_topic": true } ], "publication": { "conference_name": null, "date": "2026 Jun 6", "date_precision": "day", "issue": "", "normalized_date": "2026-06-06", "pages": "", "proceedings_title": null, "publisher": "", "title": "Journal of the American Chemical Society", "volume": "", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "Size of Biomolecular Condensates Dictates Fate in Liquid-Solid Phase Transitions through Amorphous-Amyloid Competition.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Since the publication of the 2021 WHO classification of thoracic tumors, our knowledge of pulmonary neuroendocrine neoplasms (NENs) has expanded significantly, particularly through elucidation of molecular pathways and proposals to refine the histopathological classification. This expanded knowledge across all aspects of pulmonary NENs holds promise for more precise stratification of neuroendocrine tumors (NETs) and potential development of novel, subtype-specific therapeutic strategies for all NENs. Based on our comprehensive review of the current pulmonary NEN landscape, our multidisciplinary expert panel has deliberated on the modification and updating of the 2021 classification, resulting in the proposal of the new pulmonary carcinoid/NET classification presented in this position paper, incorporating three major points: 1) The proposed framework continues the shift from the traditional carcinoid terminology toward broader adoption of the \"NET\" nomenclature as seen in other organ systems while retaining the term \"carcinoid\" as the primary diagnostic term to ensure clear communication with thoracic clinical providers. 2) Ki-67 has been incorporated as a diagnostic criterion, aligning with practices in other NET classifications, and 3) Formal recognition of the concept of \"carcinoid/NET G3\", a rare subset of lung carcinoids characterized by increased proliferative activity but molecular features more aligned with pulmonary NETs than high-grade neuroendocrine carcinomas. This position paper on the current knowledge of pulmonary NENs, including the proposed carcinoid/NET classification, will aid accurate tumor categorization and guide treatment strategies.", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Mary Beth", "last_name": "Beasley", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null }, { "creator_type": "author", "first_name": "Mauro", "last_name": "Papotti", "name": null }, { "creator_type": "author", "first_name": "Wendy A.", "last_name": "Cooper", "name": null }, { "creator_type": "author", "first_name": "Jules L.", "last_name": "Derks", "name": null }, { "creator_type": "author", "first_name": "Lynnette", "last_name": "Fernandez-Cuesta", "name": null }, { "creator_type": "author", "first_name": "Atsuko", "last_name": "Kasajima", "name": null }, { "creator_type": "author", "first_name": "Sylvie", "last_name": "Lantuejoul", "name": null }, { "creator_type": "author", "first_name": "Giuseppe", "last_name": "Pelosi", "name": null }, { "creator_type": "author", "first_name": "Natasha", "last_name": "Rekhtman", "name": null }, { "creator_type": "author", "first_name": "Anja C.", "last_name": "Roden", "name": null }, { "creator_type": "author", "first_name": "Ernst", "last_name": "Jan M Speel", "name": null }, { "creator_type": "author", "first_name": "William D.", "last_name": "Travis", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.jtho.2026.103977" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "42251892" } }, "mesh": [], "publication": { "conference_name": null, "date": "2026 Jun 6", "date_precision": "day", "issue": "", "normalized_date": "2026-06-06", "pages": "103977", "proceedings_title": null, "publisher": "", "title": "Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer", "volume": "", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "IASLC Update on Classification of Pulmonary Neuroendocrine Neoplasms.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Water adsorbents are essential in our daily lives and in various industrial fields. The water adsorption rate is one of the most important properties of water adsorbents and should be improved to implement high-throughput devices. In this study, we focused on enlarging the pore size of MIL-101(Cr) by defect engineering for a faster water diffusion. MIL-101(Cr) terephthalate linkers were substituted with formate to create the defects. We investigated how the formate substitution influenced the pore size of MIL-101(Cr) and its water adsorption rate. Thermogravimetric measurements and pore size distribution analysis confirm the defect formation. In the evaluation of the water adsorption rate, we confirm three distinct adsorption processes with different adsorption rates, corresponding to water adsorption on the pore surface, into middle pores, and into large pores, respectively. In particular, defects in MIL-101(Cr) obviously influence the third water adsorption process into large pores, in which the water adsorption rate increases by up to 25%. It is suggested that the defect formation promotes water diffusion through an available pathway and condensed water transfer from other pores by the enlargement of windows between pores. These results can help us develop dehumidification devices with higher throughput.", "classifications": [ { "id": "Hijikata", "label": "Group Hijikata", "parent": "Tsuchiya", "type": "group" }, { "id": "Tsuchiya", "label": "Team Tsuchiya", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Masaki", "last_name": "Wadaguchi", "name": null }, { "creator_type": "author", "first_name": "Yuh", "last_name": "Hijikata", "name": null }, { "creator_type": "author", "first_name": "Hiroaki", "last_name": "Iguchi", "name": null }, { "creator_type": "author", "first_name": "Shinpei", "last_name": "Kusaka", "name": null }, { "creator_type": "author", "first_name": "Hisashi", "last_name": "Kozuka", "name": null }, { "creator_type": "author", "first_name": "Ryotaro", "last_name": "Matsuda", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/acsami.6c02618" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "42246980" } }, "mesh": [], "publication": { "conference_name": null, "date": "2026 Jun 5", "date_precision": "day", "issue": "", "normalized_date": "2026-06-05", "pages": "", "proceedings_title": null, "publisher": "", "title": "ACS applied materials & interfaces", "volume": "", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "Defect Engineering of MIL-101(Cr) for an Enhanced Water Adsorption Rate.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: Dual inhibition of epidermal growth factor receptor (EGFR) and vascular endothelial growth factor (VEGF) pathways may improve outcomes in metastatic EGFR-mutant NSCLC, but VEGF inhibitors are not universally effective. We evaluated the impact of VEGFA and VEGFR2 expressions on EGFR-TKI outcomes. METHODS: EGFR-mutant NSCLC patients from the National Cancer Center Hospital, were retrospectively analysed. The early-stage cohort comprised stage I-IIIA patients (1997-2019). The advanced-stage cohort included metastatic patients (2018-2022). VEGFA/VEGFR2 expressions were dichotomised by median transcripts per million. RESULTS: Among 447 early-stage patients (median age 66), high VEGFA was associated with smoking, TP53 co-mutation, higher Brinkman Index, and higher tumour mutation burden (all p < 0.01). High VEGFA predicted shorter relapse-free survival (HR 2.10, 95% CI 1.63-2.71, p < 0.01) and overall survival (HR 2.07, 95% CI 1.46-2.95, p < 0.01). VEGFR2 expression showed no prognostic impact. In 146 relapsed patients receiving first-line EGFR-TKIs, high VEGFA was linked to shorter progression-free survival (PFS) overall (HR 1.70,95%CI 1.13-2.56, p = 0.009), particularly for first/second-generation EGFR-TKIs (HR 1.66,95%CI 1.08-2.54 p = 0.023), but not for osimertinib (p = 0.491). In 60 advanced-stage patients on osimertinib, PFS was unaffected by VEGFA (p = 0.102). CONCLUSIONS: High VEGFA is associated with aggressive biology and inferior outcomes, correlating with shorter PFS for first/second-generation EGFR-TKIs but not for osimertinib.", "classifications": [ { "id": "Hamamoto", "label": "Group Hamamoto", "parent": "Okamoto", "type": "group" }, { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Ryoko Inaba", "last_name": "Higashiyama", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Kouya", "last_name": "Shiraishi", "name": null }, { "creator_type": "author", "first_name": "Jun", "last_name": "Miyakoshi", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Torasawa", "name": null }, { "creator_type": "author", "first_name": "Masayuki", "last_name": "Shirasawa", "name": null }, { "creator_type": "author", "first_name": "Ken", "last_name": "Masuda", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Shinno", "name": null }, { "creator_type": "author", "first_name": "Yuji", "last_name": "Matsumoto", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Okuma", "name": null }, { "creator_type": "author", "first_name": "Yukihiro", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Goto", "name": null }, { "creator_type": "author", "first_name": "Hidehito", "last_name": "Horinouchi", "name": null }, { "creator_type": "author", "first_name": "Takaaki", "last_name": "Tuchida", "name": null }, { "creator_type": "author", "first_name": "Ryuji", "last_name": "Hamamoto", "name": null }, { "creator_type": "author", "first_name": "Noboru", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Shun-Ichi", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Kohno", "name": null }, { "creator_type": "author", "first_name": "Yuichiro", "last_name": "Ohe", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41416-026-03457-3" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "42231027" } }, "mesh": [ { "descriptor": "Acrylamides", "descriptor_ui": "D000178", "major_topic": false }, { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Aged, 80 and over", "descriptor_ui": "D000369", "major_topic": false }, { "descriptor": "Aniline Compounds", "descriptor_ui": "D000814", "major_topic": false }, { "descriptor": "Carcinoma, Non-Small-Cell Lung", "descriptor_ui": "D002289", "major_topic": true }, { "descriptor": "ErbB Receptors", "descriptor_ui": "D066246", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Indoles", "descriptor_ui": "D007211", "major_topic": false }, { "descriptor": "Lung Neoplasms", "descriptor_ui": "D008175", "major_topic": true }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": false }, { "descriptor": "Prognosis", "descriptor_ui": "D011379", "major_topic": false }, { "descriptor": "Protein Kinase Inhibitors", "descriptor_ui": "D047428", "major_topic": true }, { "descriptor": "Pyrimidines", "descriptor_ui": "D011743", "major_topic": false }, { "descriptor": "Retrospective Studies", "descriptor_ui": "D012189", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Vascular Endothelial Growth Factor A", "descriptor_ui": "D042461", "major_topic": true }, { "descriptor": "Vascular Endothelial Growth Factor Receptor-2", "descriptor_ui": "D040301", "major_topic": true } ], "publication": { "conference_name": null, "date": "2026 Jun 2", "date_precision": "day", "issue": "", "normalized_date": "2026-06-02", "pages": "", "proceedings_title": null, "publisher": "", "title": "British journal of cancer", "volume": "", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "Role of VEGFA/VEGFR2 signaling in predicting clinical outcomes of EGFR-TKI treatment in EGFR-mutant non-small cell lung cancer.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "", "classifications": [ { "id": "Fujiwara", "label": "Group Fujiwara", "parent": "Fujiwara", "type": "group" }, { "id": "Fujiwara", "label": "Team Fujiwara", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Hiroki", "last_name": "Machida", "name": null }, { "creator_type": "author", "first_name": "Jun", "last_name": "Yokota", "name": null }, { "creator_type": "author", "first_name": "Hironobu", "last_name": "Fujiwara", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.matbio.2026.102027" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "42235833" } }, "mesh": [], "publication": { "conference_name": null, "date": "2026 Jun 2", "date_precision": "day", "issue": "", "normalized_date": "2026-06-02", "pages": "102027", "proceedings_title": null, "publisher": "", "title": "Matrix biology : journal of the International Society for Matrix Biology", "volume": "", "year": 2026 }, "ssbd": { "database": [], "repository": [ "ssbd-repos-000415" ] }, "title": "Corrigendum to 'Basement membrane components define the microenvironment of aggregated fibroblasts in the skin and support their aggregation in vitro' [Matrix Biology 146 (2026) 102008].", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Intrahepatic cholangiocellular carcinoma (ICC) has poor prognosis, especially with lymph node (LN) metastasis (LNM). Lysine methyltransferase SET and MYND domain-containing 2 (SMYD2) has critical roles and is reportedly associated with poor prognosis in various cancers, but the role of SMYD2 in ICC is unclear. Here, we examined the role of SMYD2 in the progression of LNM of ICC. We immunohistochemically analyzed SMYD2 expression using resected specimens first in primary ICC and then in metastatic LNs derived from ICC. For functional analyses, we then performed cell proliferation assay following SMYD2 inhibition using two ICC cell lines such as HuCCT-1 and HuH28. To explore the detailed mechanisms of LNM, immunocytochemistry and western blotting related to epithelial-mesenchymal transition (EMT) were first performed. Moreover, we performed clinically immunohistochemical staining of C-C motif chemokine receptor 7 (CCR7) in metastatic LNs, immunofluorescence staining and western blotting for functional analyses to evaluate the relationship between SMYD2 and CCR7. Finally, p65 of nuclear factor-kappa B (NF-kappaB) and phospho-p65 (Ser536) status were checked as the regulator of CCR7. Protein expression levels of SMYD2 in the primary ICC lesion were not associated with any clinicopathological characteristics or prognosis. However, SMYD2 was expressed in metastatic LNs of all cases and LNM was strongly associated with poor disease-free and overall survival also as previously reported. This study therefore aimed to clarify the molecular-biological roles for LNM by SMYD2. SMYD2 knockdown significantly inhibited ICC cell proliferation. According to subsequent EMT-related research, SMYD2 knockdown did not induce morphological changes or cadherin switching. Next, chemotaxis assay revealed that SMYD2 knockdown reduced chemotaxis in HuCCT-1 from metastatic ascites but not in HuH28 from the primary lesion. CCR7 expression in metastatic LNs was immunologically confirmed in all cases and had a positive correlation with SMYD2 expression. Decreased expression of CCR7 was observed in SMYD2-suppressed HuCCT-1 cells by immunofluorescence staining and western blotting simultaneously with the decreasing phosphorylation of p65(S536). SMYD2 could be demonstrated to express in all metastatic LNs derived from ICC and may regulate this metastatic mechanism through CCR7-dependent chemotaxis rather than EMT via the SMYD2-phospho-p65(S536)-CCR7 pathway.", "classifications": [ { "id": "Hamamoto", "label": "Group Hamamoto", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Masashi", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Hayami", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Miyamoto", "name": null }, { "creator_type": "author", "first_name": "Norihiko", "last_name": "Suzaki", "name": null }, { "creator_type": "author", "first_name": "Tomohiro", "last_name": "Yoshimura", "name": null }, { "creator_type": "author", "first_name": "Kensuke", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Yoshinobu", "last_name": "Shigekawa", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Shimizu", "name": null }, { "creator_type": "author", "first_name": "Yuji", "last_name": "Kitahata", "name": null }, { "creator_type": "author", "first_name": "Akihiro", "last_name": "Takeuchi", "name": null }, { "creator_type": "author", "first_name": "Hideki", "last_name": "Motobayashi", "name": null }, { "creator_type": "author", "first_name": "Kyohei", "last_name": "Matsumoto", "name": null }, { "creator_type": "author", "first_name": "Shogo", "last_name": "Ehata", "name": null }, { "creator_type": "author", "first_name": "Ryuji", "last_name": "Hamamoto", "name": null }, { "creator_type": "author", "first_name": "Manabu", "last_name": "Kawai", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41598-026-55155-y" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "42219452" } }, "mesh": [ { "descriptor": "Bile Duct Neoplasms", "descriptor_ui": "D001650", "major_topic": true }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Cell Proliferation", "descriptor_ui": "D049109", "major_topic": false }, { "descriptor": "Chemotaxis", "descriptor_ui": "D002633", "major_topic": true }, { "descriptor": "Cholangiocarcinoma", "descriptor_ui": "D018281", "major_topic": true }, { "descriptor": "Epithelial-Mesenchymal Transition", "descriptor_ui": "D058750", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Gene Expression Regulation, Neoplastic", "descriptor_ui": "D015972", "major_topic": false }, { "descriptor": "Histone-Lysine N-Methyltransferase", "descriptor_ui": "D011495", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Lymphatic Metastasis", "descriptor_ui": "D008207", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Receptors, CCR7", "descriptor_ui": "D054400", "major_topic": true } ], "publication": { "conference_name": null, "date": "2026 Jun 1", "date_precision": "day", "issue": "", "normalized_date": "2026-06-01", "pages": "", "proceedings_title": null, "publisher": "", "title": "Scientific reports", "volume": "", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "SMYD2 regulates lymph node metastasis derived from intrahepatic cholangiocellular carcinoma through CCR7-dependent chemotaxis.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Raman spectroscopy enables label-free identification of biological tissues, but its clinical application remains limited due to low-throughput measurements. Here, we developed a spatially multiplexed random-access Raman probe that enables simultaneous spectral acquisition from arbitrarily selected locations in vivo. Parallel acquisition of up to 1718 spectra in a single exposure has been enabled by using a custom fiber bundle in combination with a spatial light modulator. In vivo measurement of a peripheral nerve in the abdominal cavity of an anesthetized canine demonstrated the feasibility of the developed system for intraoperative tissue identification within 5 s. We further performed discriminant analysis of multipoint spectra from nerve and non-nerve regions in rats, which achieved 92.5% accuracy and sensitivity for nerve discrimination. The developed system provides a basis for efficient and accurate navigation in surgery.", "classifications": [ { "id": "Fujita", "label": "Group Fujita", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Wataru", "last_name": "Sakata", "name": null }, { "creator_type": "author", "first_name": "Atsuko", "last_name": "Fujihara", "name": null }, { "creator_type": "author", "first_name": "Taisuke", "last_name": "Ota", "name": null }, { "creator_type": "author", "first_name": "Yoshinori", "last_name": "Harada", "name": null }, { "creator_type": "author", "first_name": "Nicholas Isaac", "last_name": "Smith", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Ueda", "name": null }, { "creator_type": "author", "first_name": "Tetsuro", "last_name": "Takamatsu", "name": null }, { "creator_type": "author", "first_name": "Osamu", "last_name": "Ukimura", "name": null }, { "creator_type": "author", "first_name": "Katsumasa", "last_name": "Fujita", "name": null }, { "creator_type": "author", "first_name": "Yasuaki", "last_name": "Kumamoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1364/boe.595552" }, "pmcid": { "normalized": "PMC13271228" }, "pmid": { "normalized": "42311302" } }, "mesh": [], "publication": { "conference_name": null, "date": "2026 Jun 1", "date_precision": "day", "issue": "6", "normalized_date": "2026-06-01", "pages": "3072-3088", "proceedings_title": null, "publisher": "", "title": "Biomedical optics express", "volume": "17", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "Spatially multiplexed random-access Raman probe for in vivo tissue measurements.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "PURPOSE: To develop an intravital imaging method that comprehensively shows the mouse conventional outflow pathway at high spatiotemporal resolution and to investigate the fine structures and dynamics within this pathway. METHODS: Intravital two-photon imaging was performed using Green, Prox1-reporter, and mito-Dendra2 mice. Schlemm's canal (SC) in human patients with glaucoma was histologically evaluated. RESULTS: The intravital two-photon imaging of Green mice ubiquitously expressing enhanced green fluorescent protein (EGFP) (\"Green intravital imaging\") demonstrated the perilimbal vein (PLV), collector channels (CCs), SC, and trabecular meshwork with and without a coverslip. A wide, tubular structure with septa was identified as SC in Prox1-reporter mice. Structures reminiscent of giant vacuoles and EGFP-positive vesicle flow were observed within SC. Based on the vesicle size, mitochondria in the vesicles, and platelet-specific intravital imaging findings, these EGFP-positive vesicles were identified as platelets. Moreover, platelet flow from the PLV into SC and from SC back to the PLV via CCs, as well as fast aqueous humor flow converging toward CCs, was observed. The quantitative analysis results suggested differences in aqueous flow velocity and flow patterns within SC. Platelets were also observed in SC of patients with glaucoma. CONCLUSIONS: Green intravital imaging comprehensively showed the proximal and distal conventional outflow pathway in mice at submicrometer spatial and 64.9-ms/frame temporal resolution, allowing observation of structures reminiscent of giant vacuoles. A subset of platelets transiently entered and exited SC via CCs. Within SC, aqueous humor exhibited fast flow converging toward the CCs, with differences in flow velocity and patterns. CCs may be involved in the heterogeneous dynamics of the aqueous humor.", "classifications": [ { "id": "Higaki", "label": "Group Higaki", "parent": "Ueda", "type": "group" }, { "id": "Ueda", "label": "Team Ueda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yui", "last_name": "Urahashi", "name": null }, { "creator_type": "author", "first_name": "Yuji", "last_name": "Takihara", "name": null }, { "creator_type": "author", "first_name": "Takumi", "last_name": "Higaki", "name": null }, { "creator_type": "author", "first_name": "Takefumi", "last_name": "Shimoda", "name": null }, { "creator_type": "author", "first_name": "Sachi", "last_name": "Kojima", "name": null }, { "creator_type": "author", "first_name": "Mitsuhiro", "last_name": "Endoh", "name": null }, { "creator_type": "author", "first_name": "Yuichiro", "last_name": "Arima", "name": null }, { "creator_type": "author", "first_name": "Tomokazu", "last_name": "Fujimoto", "name": null }, { "creator_type": "author", "first_name": "Norika", "last_name": "Liu", "name": null }, { "creator_type": "author", "first_name": "Anna", "last_name": "Irie", "name": null }, { "creator_type": "author", "first_name": "Takahiro", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Teruhiko", "last_name": "Hamanaka", "name": null }, { "creator_type": "author", "first_name": "Toshihiro", "last_name": "Inoue", "name": null } ], "identifiers": { "doi": { "normalized": "10.1167/iovs.67.6.53" }, "pmcid": { "normalized": "PMC13317927" }, "pmid": { "normalized": "42360097" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Aqueous Humor", "descriptor_ui": "D001082", "major_topic": true }, { "descriptor": "Disease Models, Animal", "descriptor_ui": "D004195", "major_topic": false }, { "descriptor": "Glaucoma", "descriptor_ui": "D005901", "major_topic": true }, { "descriptor": "Green Fluorescent Proteins", "descriptor_ui": "D049452", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Intraocular Pressure", "descriptor_ui": "D007429", "major_topic": false }, { "descriptor": "Intravital Microscopy", "descriptor_ui": "D000069416", "major_topic": true }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Transgenic", "descriptor_ui": "D008822", "major_topic": false }, { "descriptor": "Microscopy, Fluorescence, Multiphoton", "descriptor_ui": "D036641", "major_topic": true }, { "descriptor": "Schlemm's Canal", "descriptor_ui": "D000092662", "major_topic": true }, { "descriptor": "Trabecular Meshwork", "descriptor_ui": "D014129", "major_topic": true } ], "publication": { "conference_name": null, "date": "2026 Jun 1", "date_precision": "day", "issue": "6", "normalized_date": "2026-06-01", "pages": "53", "proceedings_title": null, "publisher": "", "title": "Investigative ophthalmology & visual science", "volume": "67", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "Comprehensive, High-Spatiotemporal-Resolution Intravital Two-Photon Imaging of the Mouse Conventional Outflow Pathway: Green Intravital Imaging.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Epithelial morphogenesis generates complex tissue architectures with remarkable reproducibility, yet how tissue-scale epithelial curvature transitions are triggered in vivo remains poorly understood. Here, we show that epithelial morphogenesis during early pupal development of the Drosophila wing disc is regulated non-autonomously through spatially restricted remodeling of the basal extracellular matrix (ECM) by neighboring tissues. Live imaging analyses reveal a previously unrecognized morphogenetic event at the larval-to-pupal stage, in which the wing disc epithelium undergoes a concave-to-convex curvature inversion. This curvature inversion is preceded by local loss of Collagen IV from the basal ECM, particularly in the notum and hinge regions. Rather than being driven autonomously by the epithelium, the shape change depends on adjacent non-epithelial cell populations, including myoblasts and tracheal cells, whose dynamic behaviors are spatially and temporally associated with basal ECM disassembly. Mechanistically, systemic ecdysone signaling activates Mmp1 and Mmp2 in these neighboring tissues, leading to localized basal ECM disassembly that permissively enables epithelial self-organization. Together, our findings identify extrinsic ECM remodeling at tissue interfaces as a non-autonomous regulatory layer that spatially licenses tissue-scale epithelial curvature transitions during development.", "classifications": [ { "id": "Sato", "label": "Group Sato", "parent": "Tsuchiya", "type": "group" }, { "id": "Tsuchiya", "label": "Team Tsuchiya", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Chigusa", "last_name": "Hinata", "name": null }, { "creator_type": "author", "first_name": "Hirotatsu", "last_name": "Nakagawa", "name": null }, { "creator_type": "author", "first_name": "Shigenori", "last_name": "Nonaka", "name": null }, { "creator_type": "author", "first_name": "Katsuya", "last_name": "Nozaki", "name": null }, { "creator_type": "author", "first_name": "Yoshikatsu", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Shizue", "last_name": "Ohsawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s42003-026-10376-9" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "42209782" } }, "mesh": [], "publication": { "conference_name": null, "date": "2026 May 29", "date_precision": "day", "issue": "", "normalized_date": "2026-05-29", "pages": "", "proceedings_title": null, "publisher": "", "title": "Communications biology", "volume": "", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "Extrinsic MMPs drive epithelial shape change via basal extracellular matrix disassembly in the Drosophila wing disc.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The heat shock protein beta-1 (HSPB1/HSP27) is highly expressed and phosphorylated in cancer tissues. However, the precise role of HSPB1 in cancer remains unclear. In this study, we report the unexpected findings elucidating the essential role of HSPB1 in adapting amino acid deficiency by upregulating amino acid transporter SLC7A5 function. HSPB1 regulates estrogen receptor-positive (ER+) breast cancer cell proliferation in a SLC7A5-dependent manner. In response to cellular stress, which is specified as amino acid-deficient conditions, HSPB1 was phosphorylated at Ser 78 residue by stress MAPK p38. SLC7A5 is associated with phosphorylated HSPB1 for its functional activation, leading to upregulated amino acid incorporation. In addition, HSPB1 and SLC7A5 overexpression increased acetylated alpha-tubulin levels. SLC7A5 overexpression did not change acetyl-CoA level, but SLC7A5 knockdown decreased ATAT1 and induced HDAC6 upregulation. Furthermore, HSPB1 and SLC7A5 induced paclitaxel and tamoxifen resistance. Therefore, the HSPB1-SLC7A5 axis contributes to the acquisition of tolerance to both tamoxifen and paclitaxel in breast cancer cells, uncovering a novel therapeutic target against drug resistance in breast cancer.", "classifications": [ { "id": "JPMJCR2123", "label": "JPMJCR2123", "researcher": "Shinya Kuroda", "type": "grant" }, { "id": "Kuroda", "label": "Group Kuroda", "parent": "Kuroda", "type": "group" }, { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yukako", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Narumi", "last_name": "Kitayama", "name": null }, { "creator_type": "author", "first_name": "Ryuhei", "last_name": "Kudo", "name": null }, { "creator_type": "author", "first_name": "Karishma", "last_name": "Silwal", "name": null }, { "creator_type": "author", "first_name": "Shiori", "last_name": "Matsuda", "name": null }, { "creator_type": "author", "first_name": "Maki", "last_name": "Ohishi", "name": null }, { "creator_type": "author", "first_name": "Ayano", "last_name": "Ueno", "name": null }, { "creator_type": "author", "first_name": "Sanae", "last_name": "Ashitani", "name": null }, { "creator_type": "author", "first_name": "Kaori", "last_name": "Igarashi", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Masuda", "name": null }, { "creator_type": "author", "first_name": "Takamasa", "last_name": "Ishikawa", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Yasuhiro", "last_name": "Saito", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.jbc.2026.113197" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "42208896" } }, "mesh": [ { "descriptor": "Breast Neoplasms", "descriptor_ui": "D001943", "major_topic": true }, { "descriptor": "Cell Membrane", "descriptor_ui": "D002462", "major_topic": true }, { "descriptor": "Cell Proliferation", "descriptor_ui": "D049109", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Heat-Shock Proteins", "descriptor_ui": "D006360", "major_topic": false }, { "descriptor": "HSP27 Heat-Shock Proteins", "descriptor_ui": "D055551", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Large Neutral Amino Acid-Transporter 1", "descriptor_ui": "D027283", "major_topic": true }, { "descriptor": "Molecular Chaperones", "descriptor_ui": "D018832", "major_topic": true }, { "descriptor": "Phosphorylation", "descriptor_ui": "D010766", "major_topic": false } ], "publication": { "conference_name": null, "date": "2026 May 27", "date_precision": "day", "issue": "", "normalized_date": "2026-05-27", "pages": "113197", "proceedings_title": null, "publisher": "", "title": "The Journal of biological chemistry", "volume": "", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "The cellular stress sensor HSPB1 regulates the membrane localization of amino acid transporter SLC7A5 in breast cancer.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The vagus nerve connects the brain and pancreas and enhances postprandial endocrine secretion from the pancreas through cholinergic signaling, such as increasing insulin release immediately after food intake in the cephalic-phase insulin response (CPIR). Here, we investigated how obesity affects vagal regulation of pancreatic endocrine function using designer receptors exclusively activated by designer drugs (DREADDs) to manipulate vagal activity. As expected, the plasma concentration of insulin was increased by vagal activation in mice expressing the excitatory DREADD hM3Dq (M3 mice) and decreased by vagal inactivation in mice expressing inhibitory DREADD hM4Di (M4 mice). However, vagal activation in M3 mice with diet-induced obesity did not elicit an early increase in insulin and instead produced a delayed insulin decrease. Mathematical modeling showed that plasma insulin dynamics in these mice were best explained by a model incorporating both the insulin-increasing and insulin-decreasing effects of the vagus nerve. Furthermore, the insulin-decreasing effect was mediated by nitric oxide (NO)-dependent, noncholinergic signaling and was enhanced in obesity. In obese M3 mice, vagal deficiency of neuronal NO synthase (nNOS) abolished the insulin-decreasing effect and restored insulin release after vagal activation. Vagal nNOS deficiency also enhanced insulin release after voluntary feeding, consistent with the CPIR. These findings suggest that vagal NO action inhibits postprandial insulin release, particularly in obesity.", "classifications": [ { "id": "Inaba", "label": "Group Inaba", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Group Kuroda", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Emi", "last_name": "Hashiuchi", "name": null }, { "creator_type": "author", "first_name": "Yuka", "last_name": "Inaba", "name": null }, { "creator_type": "author", "first_name": "Hikaru", "last_name": "Sugimoto", "name": null }, { "creator_type": "author", "first_name": "Kumi", "last_name": "Kimura", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Mayu", "last_name": "Kajino", "name": null }, { "creator_type": "author", "first_name": "Shun-Ichiro", "last_name": "Asahara", "name": null }, { "creator_type": "author", "first_name": "Masaki", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Osamu", "last_name": "Kikuchi", "name": null }, { "creator_type": "author", "first_name": "Yoshitaka", "last_name": "Hayashi", "name": null }, { "creator_type": "author", "first_name": "Shin-Ichi", "last_name": "Horike", "name": null }, { "creator_type": "author", "first_name": "Takiko", "last_name": "Daikoku", "name": null }, { "creator_type": "author", "first_name": "Michihiro", "last_name": "Mieda", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Sakurai", "name": null }, { "creator_type": "author", "first_name": "Mashito", "last_name": "Sakai", "name": null }, { "creator_type": "author", "first_name": "Michihiro", "last_name": "Matsumoto", "name": null }, { "creator_type": "author", "first_name": "Tadahiro", "last_name": "Kitamura", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Kim", "last_name": "Ravnskjaer", "name": null }, { "creator_type": "author", "first_name": "Masato", "last_name": "Kasuga", "name": null }, { "creator_type": "author", "first_name": "Mamoru", "last_name": "Tanida", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Kuroda", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Inoue", "name": null } ], "identifiers": { "doi": { "normalized": "10.1126/scisignal.adz8805" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "42189938" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Insulin", "descriptor_ui": "D007328", "major_topic": true }, { "descriptor": "Insulin Secretion", "descriptor_ui": "D000078790", "major_topic": true }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Obese", "descriptor_ui": "D008820", "major_topic": false }, { "descriptor": "Nitric Oxide", "descriptor_ui": "D009569", "major_topic": false }, { "descriptor": "Nitric Oxide Synthase Type I", "descriptor_ui": "D052248", "major_topic": true }, { "descriptor": "Obesity", "descriptor_ui": "D009765", "major_topic": true }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Vagus Nerve", "descriptor_ui": "D014630", "major_topic": true } ], "publication": { "conference_name": null, "date": "2026 May 26", "date_precision": "day", "issue": "939", "normalized_date": "2026-05-26", "pages": "eadz8805", "proceedings_title": null, "publisher": "", "title": "Science signaling", "volume": "19", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "Vagal activation inhibits insulin release through neuronal nitric oxide synthase in obese male mice.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Chromatin is a dynamic, higher-order structure that compacts genomic DNA within the nucleus and regulates genome organization and accessibility. Chromatin is broadly classified into transcriptionally inert heterochromatin and active euchromatin based on their condensation states; however, the molecular basis underlying this condensation difference remains unresolved. In this study, we show that phosphatidylcholine-type lipid molecules are associated with heterochromatin in living cells and contribute to its physical condensation. Using label-free Raman-Brillouin microscopy, we simultaneously mapped molecular concentrations and high-frequency viscoelastic properties in a living cell at subcellular resolution. Raman imaging revealed that lipid molecules are selectively enriched in heterochromatin, and their local concentrations are correlated with the mechanical response of heterochromatin. These lipids were absent from mitotic chromosomes and reappeared in DNA-rich regions during the early G1 phase, indicating that lipid incorporation is a regulated step in the formation of heterochromatin. These results expand the molecular view of chromatin and demonstrate how simultaneous Raman-Brillouin imaging can link chemical constituents with the mechanical properties of a cell.", "classifications": [ { "id": "JPMJCR2024", "label": "JPMJCR2024", "researcher": "Motohiro Nishida", "type": "grant" }, { "id": "Nakabayashi", "label": "Group Nakabayashi", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Group Nishida", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Masato", "last_name": "Machida", "name": null }, { "creator_type": "author", "first_name": "Shinji", "last_name": "Kajimoto", "name": null }, { "creator_type": "author", "first_name": "Ren", "last_name": "Shibuya", "name": null }, { "creator_type": "author", "first_name": "Mayu", "last_name": "Isono", "name": null }, { "creator_type": "author", "first_name": "Mai", "last_name": "Watabe", "name": null }, { "creator_type": "author", "first_name": "Yukako", "last_name": "Oma", "name": null }, { "creator_type": "author", "first_name": "Kayo", "last_name": "Hibino", "name": null }, { "creator_type": "author", "first_name": "Kentaro", "last_name": "Fujii", "name": null }, { "creator_type": "author", "first_name": "Masaki", "last_name": "Okumura", "name": null }, { "creator_type": "author", "first_name": "Masahiko", "last_name": "Harata", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Shibata", "name": null }, { "creator_type": "author", "first_name": "Takakazu", "last_name": "Nakabayashi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/jacsau.6c00082" }, "pmcid": { "normalized": "PMC13213494" }, "pmid": { "normalized": "42212099" } }, "mesh": [], "publication": { "conference_name": null, "date": "2026 May 25", "date_precision": "day", "issue": "5", "normalized_date": "2026-05-25", "pages": "2798-2809", "proceedings_title": null, "publisher": "", "title": "JACS Au", "volume": "6", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "Lipids Contribute to Heterochromatin Condensation Revealed by Quantitative Raman-Brillouin Microscopy.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "In most plants, the zygote divides asymmetrically to define the body axis. In Arabidopsis thaliana, the zygote undergoes polar cell elongation with maintaining a transverse band of cortical microtubules (MTs) at the growing cell tip. How the MT band is maintained at the actively renewing tip and whether it contributes to the asymmetric zygote division remain elusive. By combining live-cell imaging, mechanical simulation, and various perturbation analyses, we demonstrate a bidirectionally interactive feedback in which the MT band forms a mechanical frame to support polar zygote elongation, and this growth increases the calculated surface tension at the zygote tip to induce MT band formation. Furthermore, after zygote elongation is complete, the MT band guides another MT band, preprophase band, to determine the accurate cell division site. Therefore, the MT band is maintained via mechanical feedback with polar cell growth, ensuring the proper asymmetric cell division of the zygote.", "classifications": [ { "id": "JPMJCR2121", "label": "JPMJCR2121", "researcher": "Minako Ueda", "type": "grant" }, { "id": "Tsugawa", "label": "Group Tsugawa", "parent": "Ueda", "type": "group" }, { "id": "Ueda", "label": "Group Ueda", "parent": "Ueda", "type": "group" }, { "id": "Ueda", "label": "Team Ueda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Zichen", "last_name": "Kang", "name": null }, { "creator_type": "author", "first_name": "Sakumi", "last_name": "Nakagawa", "name": null }, { "creator_type": "author", "first_name": "Hikari", "last_name": "Matsumoto", "name": null }, { "creator_type": "author", "first_name": "Yukitaka", "last_name": "Ishimoto", "name": null }, { "creator_type": "author", "first_name": "Tomonobu", "last_name": "Nonoyama", "name": null }, { "creator_type": "author", "first_name": "Yuga", "last_name": "Hanaki", "name": null }, { "creator_type": "author", "first_name": "Satoru", "last_name": "Tsugawa", "name": null }, { "creator_type": "author", "first_name": "Minako", "last_name": "Ueda", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41467-026-72280-4" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "42173829" } }, "mesh": [ { "descriptor": "Arabidopsis", "descriptor_ui": "D017360", "major_topic": true }, { "descriptor": "Arabidopsis Proteins", "descriptor_ui": "D029681", "major_topic": false }, { "descriptor": "Asymmetric Cell Division", "descriptor_ui": "D060049", "major_topic": true }, { "descriptor": "Cell Division", "descriptor_ui": "D002455", "major_topic": false }, { "descriptor": "Microtubules", "descriptor_ui": "D008870", "major_topic": true }, { "descriptor": "Surface Tension", "descriptor_ui": "D013500", "major_topic": false }, { "descriptor": "Zygote", "descriptor_ui": "D015053", "major_topic": true } ], "publication": { "conference_name": null, "date": "2026 May 22", "date_precision": "day", "issue": "", "normalized_date": "2026-05-22", "pages": "", "proceedings_title": null, "publisher": "", "title": "Nature communications", "volume": "", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "Temporal changes in surface tension guide microtubule organization and accurate asymmetric division of Arabidopsis zygotes.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Invasive lobular carcinoma (ILC) is a special type of breast cancer. The histological subtypes of ILC exhibit diverse morphological features, and the prognosis differs accordingly. Compared with patients with classic-ILC (C-ILC), patients with pleomorphic-ILC (P-ILC) have a worse prognosis, owing to high-grade nuclear atypia and mitotic cells. However, the molecular differences between C-ILC and P-ILC remain unclear. To address this gap, we performed spatial transcriptomic profiling on four fresh-frozen C-ILC samples and four fresh-frozen P-ILC samples, followed by confirmation of reproducibility in bulk RNA-seq datasets. We identified significant enrichment of cellular response to heat stress in P-ILC. Furthermore, molecular clustering analysis using genes differentially expressed across ILC samples in spatial transcriptome revealed that ILC has three molecular subtypes: proliferative (PR), immunoreactive (IM), and stroma-rich (ST), associated with distinct prognostic outcomes. Although these molecular subtypes did not completely correspond to C-ILC or P-ILC, PR tended to include P-ILC, and ST tended to include C-ILC. These molecular clusters exhibited features comparable to previously reported subtypes. Despite these phenotypic features, ILC is generally treated similarly to invasive ductal carcinoma (IDC), with limited consideration of molecular subtype classification. Our findings suggest that molecular profiling may more accurately reflect prognosis than conventional histological classification and may provide potential diagnostic markers and therapeutic targets.", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Momoko", "last_name": "Tokura", "name": null }, { "creator_type": "author", "first_name": "Jun", "last_name": "Nakayama", "name": null }, { "creator_type": "author", "first_name": "Hironori", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Mieko", "last_name": "Ochi", "name": null }, { "creator_type": "author", "first_name": "Miyaka", "last_name": "Umemori", "name": null }, { "creator_type": "author", "first_name": "Sho", "last_name": "Shiino", "name": null }, { "creator_type": "author", "first_name": "Masayuki", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Shin", "last_name": "Takayama", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Yamamoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/cas.70413" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "42166521" } }, "mesh": [ { "descriptor": "Breast Neoplasms", "descriptor_ui": "D001943", "major_topic": true }, { "descriptor": "Carcinoma, Lobular", "descriptor_ui": "D018275", "major_topic": true }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Gene Expression Profiling", "descriptor_ui": "D020869", "major_topic": false }, { "descriptor": "Gene Expression Regulation, Neoplastic", "descriptor_ui": "D015972", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Prognosis", "descriptor_ui": "D011379", "major_topic": false }, { "descriptor": "RNA-Seq", "descriptor_ui": "D000081246", "major_topic": false }, { "descriptor": "Sequence Analysis, RNA", "descriptor_ui": "D017423", "major_topic": false }, { "descriptor": "Spatial Transcriptomics", "descriptor_ui": "D000099285", "major_topic": false }, { "descriptor": "Transcriptome", "descriptor_ui": "D059467", "major_topic": false } ], "publication": { "conference_name": null, "date": "2026 May 21", "date_precision": "day", "issue": "", "normalized_date": "2026-05-21", "pages": "", "proceedings_title": null, "publisher": "", "title": "Cancer science", "volume": "", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "Spatial Transcriptomics and Bulk RNA-Seq Analysis Revealed Molecular Classification of Invasive Lobular Carcinoma.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "In living cells, the control of molecular diffusion is pivotal for highly fluidic membranes to serve as substrates for biochemical reactions and cytoskeletal assemblies. Lateral diffusion in membranes depends on a highly diverse and homeostatically controlled lipid composition. This complexity has limited our understanding of how diffusivity in biological membranes is regulated. In this study, we show that lipid diffusion in model membranes decreases markedly in the presence of cytosolic extracts. The reduction in lipid diffusivity can be pharmacologically inhibited by targeting phospholipase D (PLD). Conversely, lipid diffusivity was reduced when PLD alone was added to the membrane. Phosphatidic acid (PA), a direct product of PLD, diffuses slowly, and its presence reduces the diffusivity of surrounding lipids. Furthermore, we found that PLD controls the lateral diffusion of a myristoylated protein PKBR1 in Dictyostelium cells, possibly through auxiliary electrostatic interactions between cationic residues located near the lipidated tail and anionic phospholipids. In line with the role of PKBR1 in regulating phosphatidylinositol(3,4,5)-trisphosphates (PIP3), PLD overexpression suppressed the size and lifetime of PIP3 microdomains as well as the sensitivity of GPCR-mediated PIP3 elevation. Our results underscore the importance of PLD and its product PA as regulators of lipidated protein diffusivity, facilitating the dynamical lateral organization of phosphoinositides in the plasma membrane.", "classifications": [ { "id": "JPMJCR1923", "label": "JPMJCR1923", "researcher": "Satoshi Sawai", "type": "grant" }, { "id": "Sawai", "label": "Group Sawai", "parent": "Sawai", "type": "group" }, { "id": "Sawai", "label": "Team Sawai", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Gen", "last_name": "Honda", "name": null }, { "creator_type": "author", "first_name": "Chihuku", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Hidenori", "last_name": "Hashimura", "name": null }, { "creator_type": "author", "first_name": "Tomoko", "last_name": "Adachi", "name": null }, { "creator_type": "author", "first_name": "Mina", "last_name": "Fujishiro", "name": null }, { "creator_type": "author", "first_name": "Nao", "last_name": "Shimada", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Sawai", "name": null }, { "creator_type": "author", "first_name": "Miho", "last_name": "Yanagisawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1073/pnas.2608790123" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "42127117" } }, "mesh": [ { "descriptor": "Cell Membrane", "descriptor_ui": "D002462", "major_topic": true }, { "descriptor": "Dictyostelium", "descriptor_ui": "D004023", "major_topic": true }, { "descriptor": "Diffusion", "descriptor_ui": "D004058", "major_topic": false }, { "descriptor": "Phosphatidic Acids", "descriptor_ui": "D010712", "major_topic": false }, { "descriptor": "Phospholipase D", "descriptor_ui": "D010739", "major_topic": true }, { "descriptor": "Protozoan Proteins", "descriptor_ui": "D015800", "major_topic": true } ], "publication": { "conference_name": null, "date": "2026 May 19", "date_precision": "day", "issue": "20", "normalized_date": "2026-05-19", "pages": "e2608790123", "proceedings_title": null, "publisher": "", "title": "Proceedings of the National Academy of Sciences of the United States of America", "volume": "123", "year": 2026 }, "ssbd": { "database": [], "repository": [ "ssbd-repos-000365" ] }, "title": "Phospholipase D regulates on-membrane diffusivity of a myristoylated protein and defines the PIP3 patch territory.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Left-right (L-R) symmetry is a fundamental feature of bilaterian body plans, yet how it is actively maintained and corrected during development remains poorly understood. In the ascidian Ciona, embryos transiently exhibit clockwise tail twisting that is progressively reduced but stabilizes at a residual angle of approximately 10 degrees . Inhibition of retinoic acid signaling or neuromuscular activity eliminated this residual twist, restoring full bilateral symmetry. Myofibrils in both left and right muscles adopted the same left-handed helical orientation, and mechanical modeling showed that this architecture generates net torque sufficient to stabilize residual twisting against full symmetry restoration. These findings reveal how bilaterian embryos balance symmetry restoration with morphogenetic asymmetry.", "classifications": [ { "id": "Okuda", "label": "Group Okuda", "parent": "Imayoshi", "type": "group" }, { "id": "Imayoshi", "label": "Team Imayoshi", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yuki S.", "last_name": "Kogure", "name": null }, { "creator_type": "author", "first_name": "Misaki K.", "last_name": "Nishio", "name": null }, { "creator_type": "author", "first_name": "Satoru", "last_name": "Okuda", "name": null }, { "creator_type": "author", "first_name": "Kohji", "last_name": "Hotta", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/1873-3468.70358" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "42108758" } }, "mesh": [], "publication": { "conference_name": null, "date": "2026 May 10", "date_precision": "day", "issue": "", "normalized_date": "2026-05-10", "pages": "", "proceedings_title": null, "publisher": "", "title": "FEBS letters", "volume": "", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "Residual tail twisting in ascidian larvae is stabilized by asymmetric myofibrils that resist bilateral symmetry restoration.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Understanding morphogenesis increasingly requires attention to physical aspects. In complex embryonic structures comprising multiple adjacent tissues, morphogenetic change in one tissue can impose geometric constraints that shape another tissue. However, such cross-tissue physical coordination remains largely unexplored. Using zebrafish jaw development, we show that dynamic folding of the oral ectoderm drives the elongation and fusion of mandibular primordia by constraining and guiding mesenchymal cell motion. This folding is initiated by Shh signaling, mainly from the adjacent neural tube, which establishes polarized behaviors in oral ectodermal cells. Notably, this phase of mandibular formation proceeds independently of cell proliferation and relies on polarized motion of both epithelium and mesenchyme. Our findings identify a physicochemical causal chain, offering a holistic view of complex embryonic tissue shaping.", "classifications": [ { "id": "JPMJCR2025", "label": "JPMJCR2025", "researcher": "Yoshihiro Morishita", "type": "grant" }, { "id": "Morishita", "label": "Group Morishita", "parent": "Morishita", "type": "group" }, { "id": "Morishita", "label": "Team Morishita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Kazutaka", "last_name": "Hosoda", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Ohtsuka", "name": null }, { "creator_type": "author", "first_name": "Sang-Woo", "last_name": "Lee", "name": null }, { "creator_type": "author", "first_name": "Naofumi", "last_name": "Kawahira", "name": null }, { "creator_type": "author", "first_name": "Toru", "last_name": "Kawanishi", "name": null }, { "creator_type": "author", "first_name": "Yoshihiro", "last_name": "Morishita", "name": null } ], "identifiers": { "doi": { "normalized": "10.1126/sciadv.aec7997" }, "pmcid": { "normalized": "PMC13155309" }, "pmid": { "normalized": "42102186" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Proliferation", "descriptor_ui": "D049109", "major_topic": false }, { "descriptor": "Ectoderm", "descriptor_ui": "D004475", "major_topic": false }, { "descriptor": "Gene Expression Regulation, Developmental", "descriptor_ui": "D018507", "major_topic": false }, { "descriptor": "Hedgehog Proteins", "descriptor_ui": "D053823", "major_topic": false }, { "descriptor": "Mandible", "descriptor_ui": "D008334", "major_topic": true }, { "descriptor": "Mesoderm", "descriptor_ui": "D008648", "major_topic": false }, { "descriptor": "Morphogenesis", "descriptor_ui": "D009024", "major_topic": true }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Zebrafish", "descriptor_ui": "D015027", "major_topic": true } ], "publication": { "conference_name": null, "date": "2026 May 8", "date_precision": "day", "issue": "19", "normalized_date": "2026-05-08", "pages": "eaec7997", "proceedings_title": null, "publisher": "", "title": "Science advances", "volume": "12", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "A cross-tissue physicochemical causal chain underlying vertebrate mandibular morphogenesis.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Predicting isocitrate dehydrogenase (IDH) mutations in gliomas using magnetic resonance imaging (MRI) is clinically important for treatment planning. This study compared two artificial intelligence (AI) models, GliomaDepth-IDH (ResNet34-based) and GliomaVista-IDH (Vision Transformer-based), with 18 physicians (eight neuroradiologists, five neurosurgeons, and five neurosurgery residents) in predicting IDH mutation status. On the Brain Tumor Segmentation Challenge dataset, the GliomaVista-IDH AI model achieved an area under the curve (AUC) value of 0.97, significantly outperforming all physician groups. However, external validation on a Japanese cohort revealed performance degradation: GliomaDepth-IDH declined to an AUC of 0.75 and GliomaVista-IDH to 0.82, with GliomaVista-IDH showing significant calibration issues (Brier score = 0.32). High-performing physicians achieved comparable results (AUC = 0.88) with superior calibration (Brier score = 0.19). Inter-rater reliability analysis revealed substantial variability across physician groups. These findings suggest that AI models can assist many physicians, while experienced practitioners remain competitive with better-calibrated predictions in challenging domains.", "classifications": [ { "id": "Hamamoto", "label": "Group Hamamoto", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Satoshi", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Masamichi", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Manabu", "last_name": "Kinoshita", "name": null }, { "creator_type": "author", "first_name": "Mototaka", "last_name": "Miyake", "name": null }, { "creator_type": "author", "first_name": "Risa", "last_name": "Kawaguchi", "name": null }, { "creator_type": "author", "first_name": "Naoki", "last_name": "Shinojima", "name": null }, { "creator_type": "author", "first_name": "Akitake", "last_name": "Mukasa", "name": null }, { "creator_type": "author", "first_name": "Kuniaki", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Motoo", "last_name": "Nagane", "name": null }, { "creator_type": "author", "first_name": "Ryohei", "last_name": "Otani", "name": null }, { "creator_type": "author", "first_name": "Fumi", "last_name": "Higuchi", "name": null }, { "creator_type": "author", "first_name": "Shota", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Nobuhiro", "last_name": "Hata", "name": null }, { "creator_type": "author", "first_name": "Kaoru", "last_name": "Tamura", "name": null }, { "creator_type": "author", "first_name": "Kensuke", "last_name": "Tateishi", "name": null }, { "creator_type": "author", "first_name": "Ryo", "last_name": "Nishikawa", "name": null }, { "creator_type": "author", "first_name": "Hideyuki", "last_name": "Arita", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Nonaka", "name": null }, { "creator_type": "author", "first_name": "Takehiro", "last_name": "Uda", "name": null }, { "creator_type": "author", "first_name": "Junya", "last_name": "Fukai", "name": null }, { "creator_type": "author", "first_name": "Yoshiko", "last_name": "Okita", "name": null }, { "creator_type": "author", "first_name": "Naohiro", "last_name": "Tsuyuguchi", "name": null }, { "creator_type": "author", "first_name": "Yonehiro", "last_name": "Kanemura", "name": null }, { "creator_type": "author", "first_name": "Fumiyasu", "last_name": "Tsushima", "name": null }, { "creator_type": "author", "first_name": "Shingo", "last_name": "Kakeda", "name": null }, { "creator_type": "author", "first_name": "Toshiaki", "last_name": "Akashi", "name": null }, { "creator_type": "author", "first_name": "Toshiaki", "last_name": "Taoka", "name": null }, { "creator_type": "author", "first_name": "Yoshiyuki", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Kei", "last_name": "Yamada", "name": null }, { "creator_type": "author", "first_name": "Toshinori", "last_name": "Hirai", "name": null }, { "creator_type": "author", "first_name": "Minako", "last_name": "Azuma", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Yoshiura", "name": null }, { "creator_type": "author", "first_name": "Jun", "last_name": "Sese", "name": null }, { "creator_type": "author", "first_name": "Koichi", "last_name": "Ichimura", "name": null }, { "creator_type": "author", "first_name": "Yoshitaka", "last_name": "Narita", "name": null }, { "creator_type": "author", "first_name": "Ryuji", "last_name": "Hamamoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41746-026-02695-2" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "42086700" } }, "mesh": [], "publication": { "conference_name": null, "date": "2026 May 5", "date_precision": "day", "issue": "", "normalized_date": "2026-05-05", "pages": "", "proceedings_title": null, "publisher": "", "title": "NPJ digital medicine", "volume": "", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "Comparing artificial intelligence and physician performance in predicting IDH mutation status in glioma.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Antiaromatic molecules are known for their intriguing physical properties and high reactivity, which arise from their unique electronic structures. While the properties of individual antiaromatic molecules have been extensively studied, research on their assembled structures is still in the early stages. In this work, we synthesized a hydrogen-bonded organic framework, named Nor-HOF, using a stable antiaromatic molecule, Ni(II) norcorrole, as a building block. Single-crystal X-ray structure analysis revealed that Nor-HOF possesses a one-dimensional columnar structure of infinitely stacked Ni(II) norcorroles with permanent porosity. Theoretical calculations indicated that the norcorroles in Nor-HOF interact through their molecular orbitals while retaining their antiaromaticity. Furthermore, we demonstrated that the oxidation of the norcorrole columns by adsorption of I(2) into the pores enhances the electrical conductivity of Nor-HOF by approximately 1000-fold. This work opens a new perspective on exploiting the periodic structure of antiaromatic molecules for the development of advanced functional materials.", "classifications": [ { "id": "Hijikata", "label": "Group Hijikata", "parent": "Tsuchiya", "type": "group" }, { "id": "Tsuchiya", "label": "Team Tsuchiya", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Toshinobu", "last_name": "Nakajo", "name": null }, { "creator_type": "author", "first_name": "Shusaku", "last_name": "Ukai", "name": null }, { "creator_type": "author", "first_name": "Tappei", "last_name": "Tanabe", "name": null }, { "creator_type": "author", "first_name": "Yuh", "last_name": "Hijikata", "name": null }, { "creator_type": "author", "first_name": "Hiroaki", "last_name": "Iguchi", "name": null }, { "creator_type": "author", "first_name": "Shinpei", "last_name": "Kusaka", "name": null }, { "creator_type": "author", "first_name": "Kohei", "last_name": "Negita", "name": null }, { "creator_type": "author", "first_name": "Jenny", "last_name": "Pirillo", "name": null }, { "creator_type": "author", "first_name": "Shu", "last_name": "Seki", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Shinokubo", "name": null }, { "creator_type": "author", "first_name": "Ryotaro", "last_name": "Matsuda", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/jacs.5c19604" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "42080311" } }, "mesh": [], "publication": { "conference_name": null, "date": "2026 May 4", "date_precision": "day", "issue": "", "normalized_date": "2026-05-04", "pages": "", "proceedings_title": null, "publisher": "", "title": "Journal of the American Chemical Society", "volume": "", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "Infinite Stacking of Antiaromatic Ni(II) Norcorroles Formed in a Porous Hydrogen-Bonded Organic Framework.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Intracytoplasmic sperm injection (ICSI) is widely used to treat human infertility, yet its effects on offspring fertility remain unclear. As infertile gametes are used in human ICSI procedures, it has remained unclear whether the procedure per se influences fertility of the resulting offspring. Here, we report on increased abortion rates and the induction of immunotolerance breakdown in mice following ICSI. Although sperm concentration was normal, sperm from ICSI-derived males showed higher curvilinear velocity and greater amplitude of lateral head displacement, suggesting a potentially increased fertilization capacity. However, when ICSI-produced males were naturally mated with wild-type females, 27.1% of the fetuses were aborted, compared to a loss of 7.5% of fetuses in control pregnancies, despite identical H2 haplotypes. Analysis of the placenta revealed infiltrating macrophages and granulocytes, as well as increased levels of 8-oxoguanine. This was accompanied by activation of innate immunity and significant downregulation of microRNAs located in the Dlk1-Dio3 microRNA cluster. Several organs of the grand-offspring exhibited inflammation. Therefore, ICSI procedure using wild-type gametes impairs the fertility of ICSI-derived male offspring by activating innate immunity during pregnancy.", "classifications": [ { "id": "Yamamoto", "label": "Group Yamamoto", "parent": "Toyoshima", "type": "group" }, { "id": "Toyoshima", "label": "Team Toyoshima", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Mito", "last_name": "Kanatsu-Shinohara", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Shiromoto", "name": null }, { "creator_type": "author", "first_name": "Narumi", "last_name": "Ogonuki", "name": null }, { "creator_type": "author", "first_name": "Kimiko", "last_name": "Inoue", "name": null }, { "creator_type": "author", "first_name": "Keiji", "last_name": "Mochida", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Kabashima", "name": null }, { "creator_type": "author", "first_name": "Yingyi", "last_name": "Kong", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Toyokuni", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Atsuo", "last_name": "Ogura", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Shinohara", "name": null } ], "identifiers": { "doi": { "normalized": "10.1242/dev.205500" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "42095840" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Fertility", "descriptor_ui": "D005298", "major_topic": true }, { "descriptor": "Immune Tolerance", "descriptor_ui": "D007108", "major_topic": true }, { "descriptor": "Immunity, Innate", "descriptor_ui": "D007113", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "MicroRNAs", "descriptor_ui": "D035683", "major_topic": false }, { "descriptor": "Placenta", "descriptor_ui": "D010920", "major_topic": false }, { "descriptor": "Pregnancy", "descriptor_ui": "D011247", "major_topic": false }, { "descriptor": "Sperm Injections, Intracytoplasmic", "descriptor_ui": "D020554", "major_topic": true }, { "descriptor": "Spermatozoa", "descriptor_ui": "D013094", "major_topic": false } ], "publication": { "conference_name": null, "date": "2026 May 1", "date_precision": "day", "issue": "9", "normalized_date": "2026-05-01", "pages": "dev205500", "proceedings_title": null, "publisher": "", "title": "Development (Cambridge, England)", "volume": "153", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "Mouse ICSI impairs fertility of male offspring by disruption of fetomaternal tolerance.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Hydropersulfides (RSSH) are increasingly recognized as key mediators in redox signalling in mammalian cells, although their physiological functions, especially in angiogenesis, remain unknown. Direct mechanistic investigation of RSSH has been challenging due to their instability and high reactivity. To address this, donors that release RSSH in a controlled manner have been developed, enabling investigation of its biological roles. Herein, we employed thiol- and enzyme-activated RSSH donors along with mutant mouse models deficient in the Cys-SSH-producing enzyme cysteinyl-tRNA synthetase/cysteine persulfide synthase (CARS2/CPERS), to examine their role in vascular angiogenesis. We demonstrate that RSSH promotes angiogenesis via the CARS2/CPERS signalling axis and activation of the Akt-eNOS and NO-cGMP pathway. We also demonstrate that nitric oxide (NO) signalling in resistance vessels requires an intact CARS2/CPER2 pathway. These findings suggest that RSSH plays an important role in regulating angiogenesis and vascular tone.", "classifications": [ { "id": "JPMJCR2024", "label": "JPMJCR2024", "researcher": "Motohiro Nishida", "type": "grant" }, { "id": "Akaike", "label": "Group Akaike", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Group Nishida", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Reece J.", "last_name": "Lamb", "name": null }, { "creator_type": "author", "first_name": "Fifi S.", "last_name": "Ibrahim", "name": null }, { "creator_type": "author", "first_name": "Vinayak S.", "last_name": "Khodade", "name": null }, { "creator_type": "author", "first_name": "Scott P.", "last_name": "Davies", "name": null }, { "creator_type": "author", "first_name": "Kayleigh", "last_name": "Griffiths", "name": null }, { "creator_type": "author", "first_name": "Tsuyoshi", "last_name": "Takata", "name": null }, { "creator_type": "author", "first_name": "Jinjing", "last_name": "Gu", "name": null }, { "creator_type": "author", "first_name": "Tetsuro", "last_name": "Matsunaga", "name": null }, { "creator_type": "author", "first_name": "Roger J.", "last_name": "Grand", "name": null }, { "creator_type": "author", "first_name": "Francesca M.", "last_name": "Nichols", "name": null }, { "creator_type": "author", "first_name": "Alice J.", "last_name": "Barton", "name": null }, { "creator_type": "author", "first_name": "Aisah A.", "last_name": "Aubdool", "name": null }, { "creator_type": "author", "first_name": "Masanobu", "last_name": "Morita", "name": null }, { "creator_type": "author", "first_name": "Hozumi", "last_name": "Motohashi", "name": null }, { "creator_type": "author", "first_name": "Ming", "last_name": "Xian", "name": null }, { "creator_type": "author", "first_name": "Takaaki", "last_name": "Akaike", "name": null }, { "creator_type": "author", "first_name": "John P.", "last_name": "Toscano", "name": null }, { "creator_type": "author", "first_name": "Melanie", "last_name": "Madhani", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.redox.2026.104192" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "42085865" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cyclic GMP", "descriptor_ui": "D006152", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Neovascularization, Physiologic", "descriptor_ui": "D018919", "major_topic": true }, { "descriptor": "Nitric Oxide", "descriptor_ui": "D009569", "major_topic": false }, { "descriptor": "Nitric Oxide Synthase Type III", "descriptor_ui": "D052250", "major_topic": false }, { "descriptor": "Proto-Oncogene Proteins c-akt", "descriptor_ui": "D051057", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Sulfides", "descriptor_ui": "D013440", "major_topic": true } ], "publication": { "conference_name": null, "date": "2026 Apr 30", "date_precision": "day", "issue": "", "normalized_date": "2026-04-30", "pages": "104192", "proceedings_title": null, "publisher": "", "title": "Redox biology", "volume": "94", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "Hydropersulfides promote angiogenesis and preserve vascular function.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Environmental exposures can influence offspring health through epigenetic alterations in the male germline. Folate deficiency, a dietary perturbation that disrupts one-carbon metabolism and S-adenosylmethionine (SAM) production, has been linked to altered histone methylation and developmental abnormalities in offspring. However, when and how folate availability shapes the germline epigenome during spermatogenesis remains unclear. In this study, unbiased metabolomic profiling of spermatogenic cells uncovers stage-specific metabolic remodeling, including downregulation of serine-glycine-one-carbon (SGOC) metabolism in meiotic spermatocytes. Using a post-weaning folate-deficient mouse model, we investigate how folate availability influences germline epigenome establishment during spermatogenesis. Consistent with this metabolic transition, genome-wide chromatin accessibility profiling demonstrates extensive, stage-dependent remodeling under folate-deficient conditions, particularly in meiotic spermatocytes and post-meiotic spermatids. These accessibility changes display cell-type-specific genomic distributions and preferential localization to repressive chromatin compartments in post-meiotic cells. Histone modification analyses further reveal bidirectional redistribution of the active histone mark H3K4me3 in round spermatids. Although genome-wide distribution of the repressive mark H3K27me3 remains largely stable, folate deficiency alters its nuclear organization. Notably, a subset of H3K4me3 alterations established in post-meiotic cells is retained in mature sperm, providing a mechanistic link between paternal metabolic perturbation and the germline epigenome. Together, these findings demonstrate that folate availability shapes germline epigenome establishment through stage-specific metabolic and chromatin remodeling during spermatogenesis, revealing a metabolic basis for paternal environmental effects on the germline epigenome.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Ai", "last_name": "Ikuyo", "name": null }, { "creator_type": "author", "first_name": "Nozomu", "last_name": "Fuse", "name": null }, { "creator_type": "author", "first_name": "Masaru", "last_name": "Mori", "name": null }, { "creator_type": "author", "first_name": "Akiyoshi", "last_name": "Hirayama", "name": null }, { "creator_type": "author", "first_name": "Yuto", "last_name": "Yamada", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Tomoko", "last_name": "Sagi", "name": null }, { "creator_type": "author", "first_name": "Kai", "last_name": "Otsuka", "name": null }, { "creator_type": "author", "first_name": "Satoshi H.", "last_name": "Namekawa", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Yohei", "last_name": "Hayashi", "name": null }, { "creator_type": "author", "first_name": "So", "last_name": "Maezawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.64898/2026.04.23.720283" }, "pmcid": { "normalized": null }, "pmid": { "normalized": null } }, "mesh": [], "publication": { "conference_name": null, "date": "2026 Apr 28", "date_precision": "day", "issue": null, "normalized_date": "2026-04-28", "pages": null, "proceedings_title": null, "publisher": null, "title": null, "volume": null, "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "Folate-dependent one-carbon metabolism controls meiotic and post-meiotic epigenome remodeling in the male germline.", "url": "", "zotero": { "item_type": "preprint" } }, { "abstract": "BACKGROUND: Histologic descriptors such as lymphovascular invasion (LVI), visceral pleural invasion (VPI), spread through air spaces (STAS), and grading system have each been associated with adverse outcomes in lung adenocarcinoma (LUAD). However, with the exception of VPI, these features are not formally incorporated into the TNM staging system. We evaluated the prognostic value and incremental contribution of these histologic descriptors within the framework of the 9(th) edition TNM staging system. METHODS: In total, 1,745 individuals diagnosed with stage I-III invasive non-mucinous lung adenocarcinoma (NM-LUAD) were included in this study, comprising 1139 French-Canadian patients who underwent surgical resection at IUCPQ-Universite Laval (discovery cohort) and 606 patients from the National Cancer Center Hospital in Tokyo, Japan (validation cohort). The objective of this study was to assess the prognostic contribution of histologic descriptors, including STAS, and LVI, as complements to conventional 9(th) edition TNM staging. RESULTS: Grade 3 tumors, LVI, and STAS were identified in 880 (50.4%), 809 (46.4%), and 775 (44.4%) of 1745 cases, respectively. Histologic grade and LVI demonstrated the strongest associations, particularly in early-stage disease, while STAS exhibited a stage-dependent effect, being more impactful in stages II-III. VPI showed less consistent prognostic value. Incorporating these histologic descriptors into TNM staging improved prognostic model performance, with the largest gains driven by histologic grade and LVI, while STAS provided modest complementary prognostic refinement. CONCLUSION: These findings demonstrate that key histologic descriptors-including grading system, LVI, and STAS-represent robust and consistent prognostic parameters. Importantly, these descriptors provide complementary, stage-dependent information that may enhance risk stratification and inform refinement of future TNM staging frameworks, including the forthcoming 10(th) edition.", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Hanie", "last_name": "Abolfathi", "name": null }, { "creator_type": "author", "first_name": "Michael", "last_name": "Maranda-Robitaille", "name": null }, { "creator_type": "author", "first_name": "Fabien Claude", "last_name": "Lamaze", "name": null }, { "creator_type": "author", "first_name": "Manal", "last_name": "Kordahi", "name": null }, { "creator_type": "author", "first_name": "Victoria Saavedra", "last_name": "Armero", "name": null }, { "creator_type": "author", "first_name": "Michele", "last_name": "Orain", "name": null }, { "creator_type": "author", "first_name": "Pierre Olivier", "last_name": "Fiset", "name": null }, { "creator_type": "author", "first_name": "David", "last_name": "Joubert", "name": null }, { "creator_type": "author", "first_name": "Patrice", "last_name": "Desmeules", "name": null }, { "creator_type": "author", "first_name": "Andreanne", "last_name": "Gagne", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null }, { "creator_type": "author", "first_name": "Yohan", "last_name": "Bosse", "name": null }, { "creator_type": "author", "first_name": "Philippe", "last_name": "Joubert", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.jtho.2026.103895" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "42055159" } }, "mesh": [ { "descriptor": "Adenocarcinoma", "descriptor_ui": "D000230", "major_topic": true }, { "descriptor": "Adenocarcinoma of Lung", "descriptor_ui": "D000077192", "major_topic": true }, { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Lung Neoplasms", "descriptor_ui": "D008175", "major_topic": true }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Neoplasm Invasiveness", "descriptor_ui": "D009361", "major_topic": false }, { "descriptor": "Neoplasm Staging", "descriptor_ui": "D009367", "major_topic": false }, { "descriptor": "Prognosis", "descriptor_ui": "D011379", "major_topic": false }, { "descriptor": "Survival Rate", "descriptor_ui": "D015996", "major_topic": false } ], "publication": { "conference_name": null, "date": "2026 Apr 27", "date_precision": "day", "issue": "", "normalized_date": "2026-04-27", "pages": "103895", "proceedings_title": null, "publisher": "", "title": "Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer", "volume": "", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "Integrating Histologic Descriptors into the Ninth Edition TNM Staging Improves Prognostic Stratification of Lung Adenocarcinoma.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "A bromine-functionalized benzimidazole-linked porous covalent organic polymer (COP) was designed and synthesized to explore its potential for xenon/krypton (Xe/Kr) separation and systematically compared with its nonbrominated analogue. The incorporation of bromine atoms protruding into the pore channels modulates the framework polarity and creates specific host-guest interactions. Gas adsorption measurements combined with isosteric heat of adsorption analyses demonstrate that bromine functionalization significantly enhances Xe uptake and Xe/Kr selectivity relative to the nonhalogenated counterpart. (129)Xe nuclear magnetic resonance (NMR) spectroscopy provides direct insight into the adsorption behavior, revealing a bimodal pore environment in the brominated polymer during Xe adsorption, indicative of heterogeneous binding sites. Complementary computational modeling elucidates the synergistic interplay between stronger confinement effects in the smaller pores of the brominated framework and energetically favorable adsorption sites in close proximity to the bromine functionalities. This study introduces a distinct separation mechanism for Xe/Kr based on polarity-induced specific interactions rather than conventional size-shape exclusion, offering a rare and effective example of organic porous materials for noble gas separation. The findings highlight halogen functionalization as a powerful strategy for tuning noble gas adsorption energetics and selectivity in covalent organic polymers.", "classifications": [ { "id": "Hijikata", "label": "Group Hijikata", "parent": "Tsuchiya", "type": "group" }, { "id": "Tsuchiya", "label": "Team Tsuchiya", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Sattwick", "last_name": "Haldar", "name": null }, { "creator_type": "author", "first_name": "Karen M.", "last_name": "Garcia Alvarez", "name": null }, { "creator_type": "author", "first_name": "Christopher", "last_name": "Bachetzky", "name": null }, { "creator_type": "author", "first_name": "Fengxu", "last_name": "Yang", "name": null }, { "creator_type": "author", "first_name": "Arafat H.", "last_name": "Khan", "name": null }, { "creator_type": "author", "first_name": "Yuh", "last_name": "Hijikata", "name": null }, { "creator_type": "author", "first_name": "Yutong", "last_name": "Wang", "name": null }, { "creator_type": "author", "first_name": "Ankita", "last_name": "De", "name": null }, { "creator_type": "author", "first_name": "Friedrich", "last_name": "Schwotzer", "name": null }, { "creator_type": "author", "first_name": "Fanny", "last_name": "Reichmayr", "name": null }, { "creator_type": "author", "first_name": "Stefan", "last_name": "Kaskel", "name": null }, { "creator_type": "author", "first_name": "Irena", "last_name": "Senkovska", "name": null }, { "creator_type": "author", "first_name": "Jack D.", "last_name": "Evans", "name": null }, { "creator_type": "author", "first_name": "Eike", "last_name": "Brunner", "name": null }, { "creator_type": "author", "first_name": "Andreas", "last_name": "Schneemann", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/acsami.6c03481" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "42043453" } }, "mesh": [], "publication": { "conference_name": null, "date": "2026 Apr 27", "date_precision": "day", "issue": "", "normalized_date": "2026-04-27", "pages": "", "proceedings_title": null, "publisher": "", "title": "ACS applied materials & interfaces", "volume": "", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "Xenon/Krypton Separation on a Bromine Functionalized Benzimidazole-Linked Porous Covalent Organic Polymer.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Rira", "last_name": "Matsuta", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Fukushima", "name": null }, { "creator_type": "author", "first_name": "Sho", "last_name": "Tabata", "name": null }, { "creator_type": "author", "first_name": "Hideki", "last_name": "Makinoshima", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Rintaro", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Eisuke", "last_name": "Hayakawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1186/s12859-026-06456-6" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "42045852" } }, "mesh": [ { "descriptor": "Carcinoma, Renal Cell", "descriptor_ui": "D002292", "major_topic": false }, { "descriptor": "Colorectal Neoplasms", "descriptor_ui": "D015179", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Kidney Neoplasms", "descriptor_ui": "D007680", "major_topic": false }, { "descriptor": "Lung Neoplasms", "descriptor_ui": "D008175", "major_topic": false }, { "descriptor": "Metabolic Networks and Pathways", "descriptor_ui": "D053858", "major_topic": false }, { "descriptor": "Metabolome", "descriptor_ui": "D055442", "major_topic": true }, { "descriptor": "Metabolomics", "descriptor_ui": "D055432", "major_topic": true }, { "descriptor": "Small Cell Lung Carcinoma", "descriptor_ui": "D055752", "major_topic": false } ], "publication": { "conference_name": null, "date": "2026 Apr 27", "date_precision": "day", "issue": "", "normalized_date": "2026-04-27", "pages": "", "proceedings_title": null, "publisher": "", "title": "BMC bioinformatics", "volume": "", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "An enrichment-based approach to interpreting metabolomic data using differential metabolomic profiles within the iDMET framework.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Human activities increasingly disrupt global ecosystems, contributing to climate change, biodiversity loss, and emerging health threats. In response, the One Health framework has gained attention as an integrative approach encompassing human, animal, and environmental health. In a symposium at APPW2025, experts in Exposome science and Digital Transformation discussed how interdisciplinary integration can advance predictive and preventive medicine. This review summarizes five key topics: Exposome as a determinant of disease risk, epigenetic mechanisms encoding environmental memory, environmental programming of brown adipose tissue, adaptive prioritization of environmental signals, and simulation-based drug repurposing. Collectively, these studies highlight a paradigm shift from conventional linear exposure-disease models toward a systems-level understanding integrating cumulative exposures, biological memory, and predictive modeling. The convergence of Exposome science and Digital Transformation provides a foundation for advancing One Health into a predictive and actionable scientific framework.", "classifications": [ { "id": "Nishida", "label": "Group Nishida", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Takeshi", "last_name": "Yoneshiro", "name": null }, { "creator_type": "author", "first_name": "Yoshito", "last_name": "Kumagai", "name": null }, { "creator_type": "author", "first_name": "Keiko", "last_name": "Nohara", "name": null }, { "creator_type": "author", "first_name": "Shingo", "last_name": "Iwami", "name": null }, { "creator_type": "author", "first_name": "Naoki", "last_name": "Honda", "name": null }, { "creator_type": "author", "first_name": "Nobuhiko", "last_name": "Ohno", "name": null }, { "creator_type": "author", "first_name": "Motohiro", "last_name": "Nishida", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.jphyss.2026.100078" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "42061101" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Exposome", "descriptor_ui": "D000081413", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Interdisciplinary Research", "descriptor_ui": "D000075762", "major_topic": true } ], "publication": { "conference_name": null, "date": "2026 Apr 26", "date_precision": "day", "issue": "2", "normalized_date": "2026-04-26", "pages": "100078", "proceedings_title": null, "publisher": "", "title": "The journal of physiological sciences : JPS", "volume": "76", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "Toward the promotion of One Health - Part II: Interdisciplinary research cooperation between digital transformation and exposome.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Microscopy with ultraviolet surface excitation (MUSE) enables rapid fluorescence imaging of tissue surfaces, but MUSE images differ markedly from conventional hematoxylin and eosin images, making cancer delineation challenging for routine pathological practice. We investigated the feasibility of deep learning-based semantic segmentation, which assigns a class label to each pixel, for pixel-wise breast cancer detection in MUSE images. Fresh breast tissues from 30 mastectomy patients with breast cancer were stained with terbium and Hoechst and imaged by MUSE. A total of 150 cancerous images (five per case) were manually annotated into cancerous and non-cancerous classes, and 300 non-cancerous images (ten per case) were collected. Models were trained and evaluated using five-fold nested cross-validation, comparing a cancer-only (CO) model trained solely on cancerous images with a cancer plus non-cancer (CN) model trained on both cancerous and non-cancerous images. The CO model achieved a higher Dice score than the CN model (CO, 0.7478; CN, 0.7343). Sliding window-based majority voting post-processing reduced scattered false-positive areas and improved Dice scores (CO, 0.7984; CN, 0.7849). These results support the feasibility of deep learning-based semantic segmentation for visualizing breast cancer regions and provide a basis for future quantitative applications using MUSE images.", "classifications": [ { "id": "Tanaka", "label": "Group Tanaka", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Tomoya", "last_name": "Matsui", "name": null }, { "creator_type": "author", "first_name": "Ryuta", "last_name": "Nakao", "name": null }, { "creator_type": "author", "first_name": "Shunsuke", "last_name": "Tomimoto", "name": null }, { "creator_type": "author", "first_name": "Junya", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Hirohiko", "last_name": "Niioka", "name": null }, { "creator_type": "author", "first_name": "Ippei", "last_name": "Takada", "name": null }, { "creator_type": "author", "first_name": "Yoshinori", "last_name": "Harada", "name": null }, { "creator_type": "author", "first_name": "Hideo", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Eiichi", "last_name": "Konishi", "name": null }, { "creator_type": "author", "first_name": "Hajime", "last_name": "Nagahara", "name": null }, { "creator_type": "author", "first_name": "Midori", "last_name": "Morita", "name": null }, { "creator_type": "author", "first_name": "Yasuto", "last_name": "Naoi", "name": null }, { "creator_type": "author", "first_name": "Tetsuya", "last_name": "Taguchi", "name": null }, { "creator_type": "author", "first_name": "Tetsuro", "last_name": "Takamatsu", "name": null } ], "identifiers": { "doi": { "normalized": "10.1267/ahc.26-00007" }, "pmcid": { "normalized": "PMC13122366" }, "pmid": { "normalized": "42057805" } }, "mesh": [], "publication": { "conference_name": null, "date": "2026 Apr 25", "date_precision": "day", "issue": "2", "normalized_date": "2026-04-25", "pages": "101-109", "proceedings_title": null, "publisher": "", "title": "Acta histochemica et cytochemica", "volume": "59", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "Semantic Segmentation for Pixel-Wise Visualization of Breast Cancer in Deep Ultraviolet-Excited Fluorescence Images.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "High-affinity inhibitors of specific receptors are a valuable tool to elucidate cellular signaling, control biological systems and develop therapeutic drugs. Here, we report mixed squaramide thioesters as a novel electrophilic handle, demonstrating an optimal balance between nucleophile accessibility and hydrolytic stability in aqueous environments. Density function theory calculations show that the energy of the lowest unoccupied molecular orbital (LUMO) of mixed squaramide thioesters is lower compared to mixed squaramide esters, rendering them more reactive to nucleophilic attack. Synthetic access to various lysophosphatidylglucoside (LysoPtdGlc) analogues incorporating mixed squaramide thioesters as phosphate bioisosteres was readily established by condensation of mixed squaramide esters with the corresponding thiols. Next, we characterised the inhibitory activity of these analogues in biological assays of axon growth cone chemotropism in cultured primary nociceptive neurons. These synthetic analogues induce both acute and sustained (more than 12 h) inhibition of the GPR55/LysoPtdGlc signaling. This inhibition resulted in sustained antagonistic attenuation of GPR55-mediated axon chemotropism while preserving growth cone sensitivity to other GPR55-independent chemotropic signaling molecules. Our findings demonstrate the potential of thiosquaramide-based phosphate bioisosteres as highly specific inhibitors with well controlled reactivity, expanding the repertoire of modulators for lipid-sensing GPCRs.", "classifications": [ { "id": "Imayoshi", "label": "Group Imayoshi", "parent": "Imayoshi", "type": "group" }, { "id": "Imayoshi", "label": "Team Imayoshi", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Junpei", "last_name": "Abe", "name": null }, { "creator_type": "author", "first_name": "Xianyue", "last_name": "Huang", "name": null }, { "creator_type": "author", "first_name": "Nozomi", "last_name": "Ishii", "name": null }, { "creator_type": "author", "first_name": "Itaru", "last_name": "Imayoshi", "name": null }, { "creator_type": "author", "first_name": "Yoshio", "last_name": "Hirabayashi", "name": null }, { "creator_type": "author", "first_name": "Ichiro", "last_name": "Matsuo", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Kamiguchi", "name": null }, { "creator_type": "author", "first_name": "Yukishige", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Adam T.", "last_name": "Guy", "name": null }, { "creator_type": "author", "first_name": "Peter", "last_name": "Greimel", "name": null } ], "identifiers": { "doi": { "normalized": "10.1039/d5cb00231a" }, "pmcid": { "normalized": "PMC13107339" }, "pmid": { "normalized": "42039760" } }, "mesh": [], "publication": { "conference_name": null, "date": "2026 Apr 24", "date_precision": "day", "issue": "", "normalized_date": "2026-04-24", "pages": "", "proceedings_title": null, "publisher": "", "title": "RSC chemical biology", "volume": "", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "Mixed squaramide thioesters as phosphate group analogues for non-competitive antagonists of the phospholipid-sensing G protein-coupled receptor GPR55.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "", "classifications": [ { "id": "JPMJCR1926", "label": "JPMJCR1926", "researcher": "Hironobu Fujiwara", "type": "grant" }, { "id": "Fujiwara", "label": "Group Fujiwara", "parent": "Fujiwara", "type": "group" }, { "id": "Fujiwara", "label": "Team Fujiwara", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Agustin A.", "last_name": "Corbat", "name": null }, { "creator_type": "author", "first_name": "Christa G.", "last_name": "Walther", "name": null }, { "creator_type": "author", "first_name": "Laura R.", "last_name": "de la Ballina", "name": null }, { "creator_type": "author", "first_name": "Nicholas D.", "last_name": "Condon", "name": null }, { "creator_type": "author", "first_name": "Alessandro A.", "last_name": "Felder", "name": null }, { "creator_type": "author", "first_name": "Martin", "last_name": "Schatz", "name": null }, { "creator_type": "author", "first_name": "Bettina", "last_name": "Schmerl", "name": null }, { "creator_type": "author", "first_name": "Ko", "last_name": "Sugawara", "name": null }, { "creator_type": "author", "first_name": "Clara", "last_name": "Prats", "name": null }, { "creator_type": "author", "first_name": "Anna", "last_name": "Klemm", "name": null }, { "creator_type": "author", "first_name": "Kota", "last_name": "Miura", "name": null }, { "creator_type": "author", "first_name": "Paula", "last_name": "Sampaio", "name": null }, { "creator_type": "author", "first_name": "Christian", "last_name": "Tischer", "name": null }, { "creator_type": "author", "first_name": "Florian", "last_name": "Levet", "name": null }, { "creator_type": "author", "first_name": "Rocco", "last_name": "D'Antuono", "name": null }, { "creator_type": "author", "first_name": "Beth A.", "last_name": "Cimini", "name": null }, { "creator_type": "author", "first_name": "Robert", "last_name": "Haase", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41592-026-03060-7" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "42020774" } }, "mesh": [], "publication": { "conference_name": null, "date": "2026 Apr 22", "date_precision": "day", "issue": "", "normalized_date": "2026-04-22", "pages": "", "proceedings_title": null, "publisher": "", "title": "Nature methods", "volume": "", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "GloBIAS: strengthening the foundations of bioimage analysis.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Enterovirus A71 (EV-A71), a causative virus of hand, foot, and mouth disease, primarily infects and replicates in the intestine and, in severe cases, spreads to the central nervous system, leading to neurological complications. Therefore, suppressing viral replication in the intestine is important to prevent severe complications. However, the intestinal pathophysiological changes in EV-A71-infected patients remain poorly understood. In this study, we aimed to examine the intestinal response to EV-A71 infection using the intestinal microphysiological system (MPS) we previously developed using human pluripotent stem cells and microfluidic devices. The viral titers were detectable in the cell culture supernatant of the intestinal MPS for 14 days after the viral infection. Despite this, EV-A71 infection did not induce significant morphological changes in the intestinal MPS or alter the expression of epithelial cell markers, suggesting that the virus can infect the intestinal MPS without causing intestinal epithelial damage. In addition, we found that the secretion of interferons (IFNs) in the cell culture supernatant was not increased by viral infection. Interestingly, treatment with recombinant IFNs increased the expression of innate immune response-related genes and reduced viral mRNA levels. A strong association was observed between EV-A71 infection and IFN signaling in the intestinal MPS. We believe that the intestinal MPS would be a valuable platform for studying EV-A71 infection and evaluating antiviral strategies.IMPORTANCEEnterovirus A71 (EV-A71), a major cause of hand, foot, and mouth disease, primarily replicates in the intestine and can spread to the central nervous system, causing severe neurological complications. Suppressing intestinal replication is therefore critical, yet the intestinal pathophysiology of EV-A71 remains poorly understood. Here, we examined EV-A71 infection using a human pluripotent stem cell-derived intestinal microphysiological system (MPS). Viral titers were detectable in the culture supernatant for 14 days. However, EV-A71 did not induce significant morphological changes or alter epithelial marker expression, indicating persistent infection without intestinal damage. Additionally, EV-A71 infection did not enhance interferon (IFN) secretion. Treatment with recombinant IFNs increased innate immune gene expression and reduced viral mRNA, demonstrating the key role of IFN signaling in restricting infection. These findings suggest that the intestinal MPS would be a useful platform for studying EV-A71 infection and antiviral strategies.", "classifications": [ { "id": "Yamamoto", "label": "Group Yamamoto", "parent": "Toyoshima", "type": "group" }, { "id": "Toyoshima", "label": "Team Toyoshima", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Hiroki", "last_name": "Futatsusako", "name": null }, { "creator_type": "author", "first_name": "Sayaka", "last_name": "Deguchi", "name": null }, { "creator_type": "author", "first_name": "Kaori", "last_name": "Kosugi", "name": null }, { "creator_type": "author", "first_name": "Rina", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Noriyo", "last_name": "Nagata", "name": null }, { "creator_type": "author", "first_name": "Tadaki", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Kazuo", "last_name": "Takayama", "name": null } ], "identifiers": { "doi": { "normalized": "10.1128/jvi.00250-26" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "42012182" } }, "mesh": [ { "descriptor": "Enterovirus A, Human", "descriptor_ui": "D029821", "major_topic": true }, { "descriptor": "Enterovirus Infections", "descriptor_ui": "D004769", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Immunity, Innate", "descriptor_ui": "D007113", "major_topic": false }, { "descriptor": "Interferons", "descriptor_ui": "D007372", "major_topic": false }, { "descriptor": "Intestinal Mucosa", "descriptor_ui": "D007413", "major_topic": false }, { "descriptor": "Intestines", "descriptor_ui": "D007422", "major_topic": true }, { "descriptor": "Microphysiological Systems", "descriptor_ui": "D000094182", "major_topic": false }, { "descriptor": "Pluripotent Stem Cells", "descriptor_ui": "D039904", "major_topic": false }, { "descriptor": "Virus Replication", "descriptor_ui": "D014779", "major_topic": false } ], "publication": { "conference_name": null, "date": "2026 Apr 21", "date_precision": "day", "issue": "", "normalized_date": "2026-04-21", "pages": "e0025026", "proceedings_title": null, "publisher": "", "title": "Journal of virology", "volume": "", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "Modeling human enterovirus A71 infection using an intestinal microphysiological system.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Donor polymorphisms in killer-cell immunoglobulin-like receptor (KIR) and human leukocyte antigen (HLA) shapes natural killer (NK) cell activity, which may influence relapse risk after allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, comprehensive association studies have been limited by insufficient allele-level genotyping across KIR genes owing to their high sequence homology. Using high-resolution long-read genotyping of 15 KIR genes, we performed an unbiased discovery analysis in 219 allo-HSCTs for adult T-cell leukemia/lymphoma (ATL) to identify relapse-associated donor KIR/HLA polymorphisms. We tested associations for donor KIR/HLA amino acid-level combinations, accounting for linkage disequilibrium across KIR haplotypes. In addition, we validated the findings in independent cohorts. In ATL, KIR3DL1*005 or KIR3DS1*013 with glutamic acid at position 62 in the HLA-B alpha2 domain (HLA-B-D2-62E), or KIR3DL1*001/*007/015/*020 with HLA-B-D2-62V (valine) were identified as high-risk (H) combinations. Meanwhile, KIR3DL1*015 with isoleucine at position 80 in the HLA-B alpha1 domain (HLA-B-D1-80I), or KIR3DL1*001/*005/*007/*020 with HLA-B-D1-80T (threonine) were identified as low-risk (L) combinations. Compared with L-/H+ donors (N=119), L+/H-, L-/H-, and L+/H+ donors (N=80) showed reduced relapse (adjusted HR=0.36, 95% CI=0.19-0.65, P=7.5x10(-)(4)) and improved overall survival (adjusted HR=0.67, 95% CI=0.45-0.98, P=0.038). Those donors were also associated with reduced relapse in other T-cell malignancies (N=145, adjusted HR=0.37, 95% CI=0.16-0.89, P=0.026), but not in acute myeloid leukemia (N=965, P=0.77), suggesting disease specificity. Notably, low-risk combinations increased CD107a degranulation by KIR3DL1+ NK cells against HLA class I-deficient targets in vitro, consistent with enhanced NK-cell education. These findings support KIR/HLA-based donor selection and underscore the role of antitumor NK cell immunity.", "classifications": [ { "id": "Yamamoto", "label": "Group Yamamoto", "parent": "Toyoshima", "type": "group" }, { "id": "Toyoshima", "label": "Team Toyoshima", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Mari", "last_name": "Morita-Fujita", "name": null }, { "creator_type": "author", "first_name": "Shuji", "last_name": "Kawaguchi", "name": null }, { "creator_type": "author", "first_name": "Takero", "last_name": "Shindo", "name": null }, { "creator_type": "author", "first_name": "Kiyotaka", "last_name": "Izumi", "name": null }, { "creator_type": "author", "first_name": "Masakazu", "last_name": "Shimizu", "name": null }, { "creator_type": "author", "first_name": "Yuichi", "last_name": "Inadomi", "name": null }, { "creator_type": "author", "first_name": "Junya", "last_name": "Kanda", "name": null }, { "creator_type": "author", "first_name": "Mizuki", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Meiko", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Taro", "last_name": "Tsujimura", "name": null }, { "creator_type": "author", "first_name": "Shoko", "last_name": "Tarumoto", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Hidenori", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Satoko", "last_name": "Morishima", "name": null }, { "creator_type": "author", "first_name": "Yasuo", "last_name": "Morishima", "name": null }, { "creator_type": "author", "first_name": "Nobuaki", "last_name": "Nakano", "name": null }, { "creator_type": "author", "first_name": "Masayasu", "last_name": "Hayashi", "name": null }, { "creator_type": "author", "first_name": "Yasuhiko", "last_name": "Miyazaki", "name": null }, { "creator_type": "author", "first_name": "Kazunori", "last_name": "Imada", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Higuchi", "name": null }, { "creator_type": "author", "first_name": "Akihito", "last_name": "Yonezawa", "name": null }, { "creator_type": "author", "first_name": "Youko", "last_name": "Suehiro", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Yoshimitsu", "name": null }, { "creator_type": "author", "first_name": "Noriko", "last_name": "Doki", "name": null }, { "creator_type": "author", "first_name": "Yuta", "last_name": "Katayama", "name": null }, { "creator_type": "author", "first_name": "Yuta", "last_name": "Hasegawa", "name": null }, { "creator_type": "author", "first_name": "Kentaro", "last_name": "Serizawa", "name": null }, { "creator_type": "author", "first_name": "Tatsuo", "last_name": "Ichinohe", "name": null }, { "creator_type": "author", "first_name": "Takahiro", "last_name": "Fukuda", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Onizuka", "name": null }, { "creator_type": "author", "first_name": "Yoshiko", "last_name": "Atsuta", "name": null }, { "creator_type": "author", "first_name": "Akifumi", "last_name": "Takaori-Kondo", "name": null }, { "creator_type": "author", "first_name": "Fumihiko", "last_name": "Matsuda", "name": null } ], "identifiers": { "doi": { "normalized": "10.1182/bloodadvances.2025019066" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "41995743" } }, "mesh": [ { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Genotype", "descriptor_ui": "D005838", "major_topic": false }, { "descriptor": "Hematopoietic Stem Cell Transplantation", "descriptor_ui": "D018380", "major_topic": true }, { "descriptor": "HLA Antigens", "descriptor_ui": "D006680", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Lymphoma, T-Cell", "descriptor_ui": "D016399", "major_topic": true }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Polymorphism, Genetic", "descriptor_ui": "D011110", "major_topic": true }, { "descriptor": "Receptors, KIR", "descriptor_ui": "D054340", "major_topic": true }, { "descriptor": "Recurrence", "descriptor_ui": "D012008", "major_topic": false }, { "descriptor": "Tissue Donors", "descriptor_ui": "D014019", "major_topic": false } ], "publication": { "conference_name": null, "date": "2026 Apr 17", "date_precision": "day", "issue": "", "normalized_date": "2026-04-17", "pages": "bloodadvances.2025019066", "proceedings_title": null, "publisher": "", "title": "Blood advances", "volume": "", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "Long-read KIR genotyping reveals donor KIR/HLA polymorphisms linked to posttransplant relapse in T-cell malignancies.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "INTRODUCTION: Antibody-drug conjugates (ADCs) and bispecific antibodies (BiAbs) are emerging treatments for small cell lung cancer (SCLC). However, optimal patient selection remains unclear. Delta-like ligand 3 (DLL3) is a promising therapeutic target, but its clinical utility is not fully established, and data on other targetable proteins such as trophoblast cell-surface antigen 2 (TROP2) and B7-H3 remain limited. To our knowledge, no prior study has assessed multiple therapeutic targets within the same patient before and after treatment. This study examined changes in DLL3 and other targets in de novo and transformed SCLC. MATERIALS AND METHODS: We retrospectively analyzed 15 patients with SCLC (9 de novo and 6 transformed SCLC) with tumor biopsies at diagnosis and progression. Immunohistochemistry assessed DLL3, TROP2, B7-H3, MET, and HER2. H-score changes, with a >/= 100-point difference considered significant. RESULTS: In de novo SCLC, DLL3 fluctuated in 3/9 cases, B7-H3 and MET increased in 2/9 and 1/9 cases, respectively, while HER2 became negative in 1/9 case. Protein co-expression was seen in 5 of 9 cases. In transformed SCLC, DLL3 expression increased in 6/6 cases, while TROP2 and HER2 were downregulated. B7-H3 and MET showed a decreasing trend in 4/5 cases. Co-expression was observed in 3/5 cases, all showing DLL3 and B7-H3 positivity, with additional co-expression of MDM2 or MET. CONCLUSION: Therapeutic target proteins in SCLC exhibit dynamic changes, emphasizing the need for biomarker-driven strategies. Rebiopsy may guide therapeutic decisions, and further research is needed to optimize patient selection for ADCs and BiAbs.", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Saori", "last_name": "Murata", "name": null }, { "creator_type": "author", "first_name": "Jumpei", "last_name": "Kashima", "name": null }, { "creator_type": "author", "first_name": "Hidehito", "last_name": "Horinouchi", "name": null }, { "creator_type": "author", "first_name": "Satsuki", "last_name": "Kishikawa", "name": null }, { "creator_type": "author", "first_name": "Ken", "last_name": "Masuda", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Shinno", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Okuma", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Goto", "name": null }, { "creator_type": "author", "first_name": "Noboru", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Shun-Ichi", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Yuji", "last_name": "Matsumoto", "name": null }, { "creator_type": "author", "first_name": "Kae", "last_name": "Okuma", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.lungcan.2026.109418" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "42013561" } }, "mesh": [ { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Aged, 80 and over", "descriptor_ui": "D000369", "major_topic": false }, { "descriptor": "Antigens, Neoplasm", "descriptor_ui": "D000951", "major_topic": false }, { "descriptor": "Biomarkers, Tumor", "descriptor_ui": "D014408", "major_topic": true }, { "descriptor": "Biopsy", "descriptor_ui": "D001706", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Immunohistochemistry", "descriptor_ui": "D007150", "major_topic": false }, { "descriptor": "Intracellular Signaling Peptides and Proteins", "descriptor_ui": "D047908", "major_topic": false }, { "descriptor": "Lung Neoplasms", "descriptor_ui": "D008175", "major_topic": true }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Membrane Proteins", "descriptor_ui": "D008565", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Retrospective Studies", "descriptor_ui": "D012189", "major_topic": false }, { "descriptor": "Small Cell Lung Carcinoma", "descriptor_ui": "D055752", "major_topic": true } ], "publication": { "conference_name": null, "date": "2026 Apr 17", "date_precision": "day", "issue": "", "normalized_date": "2026-04-17", "pages": "109418", "proceedings_title": null, "publisher": "", "title": "Lung cancer (Amsterdam, Netherlands)", "volume": "216", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "Comparative analysis of therapeutic target protein expression in de novo and transformed small cell lung carcinomas using paired biopsy samples.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Trichalcogenides with linearly catenated chalcogen atoms (S, Se, and Te), exemplified by glutathione trisulfide, are increasingly recognized as key regulators of biological redox processes. However, their robust structural characterization remains limited because the NMR-active sulfur isotope ((33)S, I = 3/2) is low-abundance and quadrupolar. The examination of chalcogen connection in heterologous trichalcogenides remains highly challenging. Recent studies have examined (77)Se and (125)Te as replacements for sulfur and applied (77)Se/(125)Te NMR in biomolecules. In this study, we report the in situ synthesis of heterologous trichalcogenides of glutathione disulfide (GS-SG) by inserting a single chalcogen atom into a disulfide bond using chalcogen donors in a conventional NMR tube. The NMR-active isotopes (77)Se and (125)Te (I = 1/2) provide broad chemical-shift ranges and high sensitivity to structural and dynamic changes, enabling multinuclear NMR. (1)H DOSY and quantitative (1)H NMR confirm a single major species (>95% by NMR) and (1)H-detected (77)Se/(125)Te heteronuclear multiple-bond correlation experiments demonstrate long-range coherence transfers. Heavy chalcogen insertion causes greater structural perturbation, making Se more suitable than Te. Density functional theory calculation revealed a smaller highest occupied molecular orbital-lowest unoccupied molecular orbital gap for GS-Te-SG, indicating its lower thermodynamic stability than GS-Se-SG. Consistent results were observed in the cystine-based experiments. To the best of our knowledge, for the first time, this study demonstrated that Se or Te can be inserted into the central site of disulfide bonding. In the biological assays, glutathione derivatives incorporating heavier chalcogens exhibit antiradical activities. This in situ synthetic and analytical framework expands the chemical space of biologically relevant chalcogenides.", "classifications": [ { "id": "Akaike", "label": "Group Akaike", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Kazuma", "last_name": "Murakami", "name": null }, { "creator_type": "author", "first_name": "Keisuke", "last_name": "Tao-Kakuyama", "name": null }, { "creator_type": "author", "first_name": "Thi Hong Van", "last_name": "Nguyen", "name": null }, { "creator_type": "author", "first_name": "Katsutoshi", "last_name": "Nishino", "name": null }, { "creator_type": "author", "first_name": "Takaaki", "last_name": "Akaike", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/acsmeasuresciau.5c00193" }, "pmcid": { "normalized": "PMC13087926" }, "pmid": { "normalized": "42007060" } }, "mesh": [], "publication": { "conference_name": null, "date": "2026 Apr 15", "date_precision": "day", "issue": "2", "normalized_date": "2026-04-15", "pages": "466-475", "proceedings_title": null, "publisher": "", "title": "ACS measurement science au", "volume": "6", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "Exploring Chalcogen Connection in Glutathione Trichalcogenides via (1)H‑Detected (77)Se/(125)Te NMR.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "", "classifications": [ { "id": "Hamamoto", "label": "Group Hamamoto", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Eri", "last_name": "Suzuki-Ariyoshi", "name": null }, { "creator_type": "author", "first_name": "Syuzo", "last_name": "Kaneko", "name": null }, { "creator_type": "author", "first_name": "Kenbun", "last_name": "Sone", "name": null }, { "creator_type": "author", "first_name": "Noriko", "last_name": "Ikawa", "name": null }, { "creator_type": "author", "first_name": "Ryuta", "last_name": "Hachijo", "name": null }, { "creator_type": "author", "first_name": "Yuri", "last_name": "Jonouchi", "name": null }, { "creator_type": "author", "first_name": "Natsumi", "last_name": "Tsuboyama", "name": null }, { "creator_type": "author", "first_name": "Ayumi", "last_name": "Taguchi", "name": null }, { "creator_type": "author", "first_name": "Ken", "last_name": "Asada", "name": null }, { "creator_type": "author", "first_name": "Masaaki", "last_name": "Komatsu", "name": null }, { "creator_type": "author", "first_name": "Takayuki", "last_name": "Iriyama", "name": null }, { "creator_type": "author", "first_name": "Katsutoshi", "last_name": "Oda", "name": null }, { "creator_type": "author", "first_name": "Yutaka", "last_name": "Osuga", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Hirota", "name": null }, { "creator_type": "author", "first_name": "Ryuji", "last_name": "Hamamoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41598-026-48676-z" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "41986648" } }, "mesh": [ { "descriptor": "Adenocarcinoma, Clear Cell", "descriptor_ui": "D018262", "major_topic": true }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Epigenesis, Genetic", "descriptor_ui": "D044127", "major_topic": true }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Gene Expression Regulation, Neoplastic", "descriptor_ui": "D015972", "major_topic": false }, { "descriptor": "Histone-Lysine N-Methyltransferase", "descriptor_ui": "D011495", "major_topic": true }, { "descriptor": "Histones", "descriptor_ui": "D006657", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Ovarian Neoplasms", "descriptor_ui": "D010051", "major_topic": true } ], "publication": { "conference_name": null, "date": "2026 Apr 15", "date_precision": "day", "issue": "", "normalized_date": "2026-04-15", "pages": "", "proceedings_title": null, "publisher": "", "title": "Scientific reports", "volume": "", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "SETD8 promotes ovarian clear cell carcinoma by epigenetically activating RNA metabolism genes via H4K20me1.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Cells can adapt to various environments by changing their biomolecular profiles while maintaining physiological homeostasis. What organizational principles in cells enable the simultaneous realization of adaptability and homeostasis? To address this question, we measure Raman scattering light from Escherichia coli cells under diverse conditions, whose spectral patterns convey their comprehensive molecular composition. We reveal that dimension-reduced Raman spectra can predict condition-dependent proteome profiles. Quantitative analysis of the Raman-proteome correspondence characterizes a low-dimensional hierarchical stoichiometry-conserving proteome structure. The network centrality of each gene in the stoichiometry conservation relations correlates with its essentiality and evolutionary conservation, and these correlations are preserved from bacteria to human cells. Furthermore, stoichiometry-conserving core components obey growth law and ensure homeostasis across conditions, whereas peripheral stoichiometry-conserving components enable adaptation to specific conditions. Mathematical analysis reveals that the stoichiometrically constrained architecture is reflected in major changes in Raman spectral patterns. These results uncover coordination of global stoichiometric balance in cells and demonstrate that vibrational spectroscopy can decipher such biological constraints beyond statistical or machine-learning inference of cellular states.", "classifications": [ { "id": "JPMJCR1927", "label": "JPMJCR1927", "researcher": "Yuichi Wakamoto", "type": "grant" }, { "id": "Wakamoto", "label": "Group Wakamoto", "parent": "Wakamoto", "type": "group" }, { "id": "Wakamoto", "label": "Team Wakamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Ken-Ichiro F.", "last_name": "Kamei", "name": null }, { "creator_type": "author", "first_name": "Koseki J.", "last_name": "Kobayashi-Kirschvink", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Nozoe", "name": null }, { "creator_type": "author", "first_name": "Hidenori", "last_name": "Nakaoka", "name": null }, { "creator_type": "author", "first_name": "Miki", "last_name": "Umetani", "name": null }, { "creator_type": "author", "first_name": "Yuichi", "last_name": "Wakamoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.7554/elife.101485" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "41978371" } }, "mesh": [ { "descriptor": "Escherichia coli", "descriptor_ui": "D004926", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Proteome", "descriptor_ui": "D020543", "major_topic": true }, { "descriptor": "Spectrum Analysis, Raman", "descriptor_ui": "D013059", "major_topic": true } ], "publication": { "conference_name": null, "date": "2026 Apr 14", "date_precision": "day", "issue": "", "normalized_date": "2026-04-14", "pages": "RP101485", "proceedings_title": null, "publisher": "", "title": "eLife", "volume": "14", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "Revealing global stoichiometry conservation architecture in cells from Raman spectral patterns.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Sulfide:quinone oxidoreductase (SQR) is a critical enzyme that maintains sulfur metabolism by oxidizing sulfide to supersulfides, currently defined as sulfur metabolites with six valence electrons and no charge that are covalently catenated with other sulfur atoms and excludes disulfides. While SQR is known to contribute to mitochondrial electron transport, its physiological impact on systemic energy metabolism and longevity remains largely undefined. In this study, we investigated the role of SQR in mitochondrial bioenergetics and aging using SQR-deficient Schizosaccharomyces pombe (Δhmt2) and a mitochondria-selective SQR-deficient (Sqrdl (ΔN/ΔN)) mice model. Functional analysis demonstrated that Δhmt2 grew normally in glucose but not in glycerol, indicating impaired mitochondrial respiration. It showed reduced membrane potential, ATP, and lifespan. Consistent with the yeast findings, Sqrdl (ΔN/ΔN) mice exhibited accumulated levels of hydrogen sulfide and persulfides, and demonstrated impaired mitochondrial energy metabolism. Furthermore, supersulfide donor supplementation selectively conferred lifespan extension in wild-type yeast, but not in SQR-deficient strain, and similarly improved mitochondrial function exclusively in wild-type mouse embryonic fibroblasts, with no benefit observed in SQR-mutant counterparts. Together, our findings demonstrate that mitochondrial SQR plays an essential role in sulfur respiration, critically supporting mitochondrial function and organismal longevity across eukaryotes.", "classifications": [ { "id": "JPMJCR2024", "label": "JPMJCR2024", "researcher": "Motohiro Nishida", "type": "grant" }, { "id": "Akaike", "label": "Group Akaike", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Group Nishida", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Jia", "last_name": "Yao", "name": null }, { "creator_type": "author", "first_name": "Tetsuro", "last_name": "Matsunaga", "name": null }, { "creator_type": "author", "first_name": "Akira", "last_name": "Nishimura", "name": null }, { "creator_type": "author", "first_name": "Meg", "last_name": "Shieh", "name": null }, { "creator_type": "author", "first_name": "Tomoaki", "last_name": "Ida", "name": null }, { "creator_type": "author", "first_name": "Minkyung", "last_name": "Jung", "name": null }, { "creator_type": "author", "first_name": "Seiryo", "last_name": "Ogata", "name": null }, { "creator_type": "author", "first_name": "Tsuyoshi", "last_name": "Takata", "name": null }, { "creator_type": "author", "first_name": "Uladzimir", "last_name": "Barayeu", "name": null }, { "creator_type": "author", "first_name": "Hozumi", "last_name": "Motohashi", "name": null }, { "creator_type": "author", "first_name": "Masanobu", "last_name": "Morita", "name": null }, { "creator_type": "author", "first_name": "Takaaki", "last_name": "Akaike", "name": null } ], "identifiers": { "doi": { "normalized": "10.64898/2026.04.05.716515" }, "pmcid": { "normalized": null }, "pmid": { "normalized": null } }, "mesh": [], "publication": { "conference_name": null, "date": "2026 Apr 7", "date_precision": "day", "issue": null, "normalized_date": "2026-04-07", "pages": null, "proceedings_title": null, "publisher": null, "title": null, "volume": null, "year": 2026 }, "ssbd": { "database": [], "repository": [ "ssbd-repos-000521" ] }, "title": "Sulfide:quinone oxidoreductase drives mitochondrial supersulfide metabolism to regulate bioenergetics and longevity in eukaryotes.", "url": "", "zotero": { "item_type": "preprint" } }, { "abstract": "BACKGROUND: The standard treatment for stage III colorectal cancer (CRC) is surgery, followed by adjuvant chemotherapy (AC). However, the efficacy of AC is limited and approximately 30% of patients experience recurrence. Therefore, easily assessable molecular biomarkers that can predict the response to AC are needed. Here, we aimed to identify predictive biomarkers of the response to AC using tumor transcriptomic data. METHODS: Tumor specimens from 253 patients who underwent surgery for stage III CRC between 1997 and 2019 were analyzed using RNA sequencing. Transcriptional subtyping and analyses of gut microbiome, immune cell fractions, and T-cell receptors (TCRs) were performed to identify factors associated with recurrence-free survival (RFS) in patients treated with or without AC. RESULTS: Among 253 patients, 118 (46.6%) received AC. Twenty phyla and 799 species were identified in the microbiomes, among which Fusobacteria were identified in 247 patients (97.6%). Multivariable Cox proportional hazards regression analysis of patients who received AC showed that intratumoral Fusobacterium abundance (hazard ratio [HR], 3.95; 95% confidence interval [CI], 1.05 to 14.8; P = 0.042) and TCR alpha and delta (TRAD) diversity (HR, 0.41; 95% CI, 0.20 to 0.87; P = 0.020) were independently associated with RFS. CONCLUSION: Fusobacterium abundance and TRAD diversity were associated with the response to AC, suggesting that these factors could serve as biomarkers for personalized treatment in stage III CRC.", "classifications": [ { "id": "Hamamoto", "label": "Group Hamamoto", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Erika", "last_name": "Machida", "name": null }, { "creator_type": "author", "first_name": "Yasuyuki", "last_name": "Takamizawa", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Takayanagi", "name": null }, { "creator_type": "author", "first_name": "Hourin", "last_name": "Cho", "name": null }, { "creator_type": "author", "first_name": "Dai", "last_name": "Shida", "name": null }, { "creator_type": "author", "first_name": "Masayoshi", "last_name": "Yamada", "name": null }, { "creator_type": "author", "first_name": "Yuka", "last_name": "Asami", "name": null }, { "creator_type": "author", "first_name": "Hanako", "last_name": "Ono", "name": null }, { "creator_type": "author", "first_name": "Mai", "last_name": "Takeuchi", "name": null }, { "creator_type": "author", "first_name": "Ryuji", "last_name": "Hamamoto", "name": null }, { "creator_type": "author", "first_name": "Toshiki", "last_name": "Rikiyama", "name": null }, { "creator_type": "author", "first_name": "Koichi", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Yukihide", "last_name": "Kanemitsu", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Kohno", "name": null }, { "creator_type": "author", "first_name": "Atsuo", "last_name": "Takashima", "name": null }, { "creator_type": "author", "first_name": "Shigeki", "last_name": "Sekine", "name": null }, { "creator_type": "author", "first_name": "Kouya", "last_name": "Shiraishi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1093/jncics/pkag036" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "41965123" } }, "mesh": [ { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Biomarkers, Tumor", "descriptor_ui": "D014408", "major_topic": true }, { "descriptor": "Chemotherapy, Adjuvant", "descriptor_ui": "D017024", "major_topic": false }, { "descriptor": "Colorectal Neoplasms", "descriptor_ui": "D015179", "major_topic": true }, { "descriptor": "Disease-Free Survival", "descriptor_ui": "D018572", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Gastrointestinal Microbiome", "descriptor_ui": "D000069196", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Neoplasm Recurrence, Local", "descriptor_ui": "D009364", "major_topic": false }, { "descriptor": "Neoplasm Staging", "descriptor_ui": "D009367", "major_topic": false }, { "descriptor": "Proportional Hazards Models", "descriptor_ui": "D016016", "major_topic": false }, { "descriptor": "Receptors, Antigen, T-Cell", "descriptor_ui": "D011948", "major_topic": false }, { "descriptor": "Treatment Outcome", "descriptor_ui": "D016896", "major_topic": false } ], "publication": { "conference_name": null, "date": "2026 Apr 6", "date_precision": "day", "issue": "", "normalized_date": "2026-04-06", "pages": "pkag036", "proceedings_title": null, "publisher": "", "title": "JNCI cancer spectrum", "volume": "", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "Microbiomic and immunogenic biomarkers of adjuvant chemotherapy efficacy in stage III colorectal cancer.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The pituitary gland plays a central role in maintaining physiological homeostasis by secreting multiple hormones that regulate diverse body functions. Dysregulation of pituitary hormones can arise from various conditions, such as pituitary tumors and autoimmune diseases, leading to a broad spectrum of symptoms. During embryonic organogenesis, the pituitary gland originates from the oral ectoderm in close contact with the adjacent hypothalamus. This tissue interaction is essential for proper development. Although the molecular mechanisms underlying pituitary development and related disorders have been extensively studied using animal models, such as rodents and zebrafish, species-specific differences limit the translatability of these findings to humans. Moreover, the scarcity of established human pituitary cell lines has hindered the investigation of human-specific mechanisms. Recent biotechnological advances have addressed these limitations by enabling the long-term culture of human pituitary tumor tissues and in vitro generation of pituitary hormone-producing cells from human pluripotent stem cells. These emerging platforms provide powerful tools for deepening our understanding of pituitary biology and diseases. In this review, we summarize current in vitro experimental models derived from pituitary tissues and pluripotent stem cells and discussed their applications in the study of pituitary development, physiology, and related disorders.", "classifications": [ { "id": "Yamamoto", "label": "Group Yamamoto", "parent": "Toyoshima", "type": "group" }, { "id": "Toyoshima", "label": "Team Toyoshima", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Ryusaku", "last_name": "Matsumoto", "name": null }, { "creator_type": "author", "first_name": "Ayaka", "last_name": "Nishio", "name": null }, { "creator_type": "author", "first_name": "Yutaka", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Yamamoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1507/endocrj.ej25-0601" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "41936431" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Models, Biological", "descriptor_ui": "D008954", "major_topic": false }, { "descriptor": "Pituitary Diseases", "descriptor_ui": "D010900", "major_topic": true }, { "descriptor": "Pituitary Gland", "descriptor_ui": "D010902", "major_topic": true }, { "descriptor": "Pituitary Neoplasms", "descriptor_ui": "D010911", "major_topic": false }, { "descriptor": "Pluripotent Stem Cells", "descriptor_ui": "D039904", "major_topic": true } ], "publication": { "conference_name": null, "date": "2026 Apr 3", "date_precision": "day", "issue": "", "normalized_date": "2026-04-03", "pages": "", "proceedings_title": null, "publisher": "", "title": "Endocrine journal", "volume": "", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "Emerging human cell-based in vitro models for studying pituitary development and disorders.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Cell polarization is a fundamental process in establishing the body axis during plant embryogenesis. In Arabidopsis thaliana, this process encompasses the zygote asymmetry that establishes the apical-basal axis and the subsequent embryo patterning that generates the radial axis. In this review, we summarize recent advances that have transformed our understanding of these events by integrating genetic and mathematical perspectives. We first describe how the embryo repurposes conserved signaling modules to regulate axis formation. In particular, we highlight emerging evidence that early transcriptional networks initiated by parental factors not only directly regulate zygote polarization but also predetermine subsequent developmental programs. Beyond molecular genetics, we discuss how the integration of advanced live-cell imaging and computational modeling provides a powerful approach to elucidate the polar cell elongation and geometric rule underlying embryo patterning. We emphasize the synergy between these mechanisms, illustrating how genetic factors modulate cellular behaviors to direct apical-basal and radial patterning. Finally, we provide future perspectives on comparative developmental studies and emerging technologies that are poised to uncover the evolutionary principles governing plant embryogenesis.", "classifications": [ { "id": "JPMJCR2121", "label": "JPMJCR2121", "researcher": "Minako Ueda", "type": "grant" }, { "id": "Ueda", "label": "Group Ueda", "parent": "Ueda", "type": "group" }, { "id": "Ueda", "label": "Team Ueda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yusuke", "last_name": "Kimata", "name": null }, { "creator_type": "author", "first_name": "Minako", "last_name": "Ueda", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.pbi.2026.102874" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "41955758" } }, "mesh": [ { "descriptor": "Arabidopsis", "descriptor_ui": "D017360", "major_topic": true }, { "descriptor": "Body Patterning", "descriptor_ui": "D019521", "major_topic": false }, { "descriptor": "Cell Polarity", "descriptor_ui": "D016764", "major_topic": true }, { "descriptor": "Gene Expression Regulation, Plant", "descriptor_ui": "D018506", "major_topic": false }, { "descriptor": "Seeds", "descriptor_ui": "D012639", "major_topic": true }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false } ], "publication": { "conference_name": null, "date": "2026 Apr 1", "date_precision": "day", "issue": "", "normalized_date": "2026-04-01", "pages": "102874", "proceedings_title": null, "publisher": "", "title": "Current opinion in plant biology", "volume": "91", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "Orchestrating polarity in embryo: From molecular programming to geometric rules.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Gas chromatography/mass spectrometry (GC/MS) is widely employed in metabolomics owing to its high resolution, reproducibility, and compatibility with volatile and semi-volatile compounds. While helium has traditionally been used as the carrier gas, increasing costs and global shortages have prompted the exploration of hydrogen gas as an alternative. Hydrogen offers faster analysis times and reduced ion source contamination but presents challenges, including ion source reactions, which can change compound fragmentation patterns. To address this, a hydrogen-deactivated electron ionization (EI) source has been developed to minimize undesired chemical interactions and improve spectral integrity. In this study, we systematically evaluated the effect of extraction lens sizes (3, 6, and 9 mm) under hydrogen carrier gas conditions using n-alkane and human metabolomic standard solutions. The hydrogen-deactivated ion source equipped with a 3 mm extraction lens provided superior peak symmetry and the highest signal intensities, with acceptable relative standard deviation (RSD) values (i.e., below 30%). In addition, the reproducible fragmentation patterns as those observed with helium carrier gas were obtained for phosphorylated metabolites. Using this optimized configuration, we applied hydrogen gas-based GC/MS to metabolomic profiling of the human colon cancer cell line HCT116 with mutant isocitrate dehydrogenase 1 (IDH1). Key metabolic alterations, including increased levels of the known biomarker 2-hydroxyglutaric acid, were detected in IDH1-mutant cells compared with wild-type cells. These findings establish hydrogen gas-based GC/MS with a hydrogen-deactivated ion source as a robust and reliable platform for metabolomics, offering an effective alternative to helium-based systems.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Momo", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Ryosuke", "last_name": "Hayasaka", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Akiyoshi", "last_name": "Hirayama", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.chroma.2026.466945" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "41931901" } }, "mesh": [ { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Gas Chromatography-Mass Spectrometry", "descriptor_ui": "D008401", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Hydrogen", "descriptor_ui": "D006859", "major_topic": true }, { "descriptor": "Metabolome", "descriptor_ui": "D055442", "major_topic": false }, { "descriptor": "Metabolomics", "descriptor_ui": "D055432", "major_topic": true }, { "descriptor": "Reproducibility of Results", "descriptor_ui": "D015203", "major_topic": false } ], "publication": { "conference_name": null, "date": "2026 Mar 28", "date_precision": "day", "issue": "", "normalized_date": "2026-03-28", "pages": "466945", "proceedings_title": null, "publisher": "", "title": "Journal of chromatography. A", "volume": "1776", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "Optimization of lens size and ion source parameters for gas chromatography/mass spectrometry-based metabolomics using hydrogen as a carrier gas.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "INTRODUCTION: Minimal residual disease (MRD) detection using liquid biopsy is an emerging tool for risk stratification and monitoring for recurrence in resected early-stage NSCLC. There is increasing need for clear guidance on its optimal clinical implementation. METHODS: The Asian Thoracic Oncology Research Group (ATORG) convened a multi-disciplinary panel of 27 experts to develop a consensus statement on the clinical application of ctDNA-based MRD testing in early-stage resected NSCLC, using a structured Delphi methodology. Statements were organized into broad thematic domains: Assay validity and standardization; Harmonization in research and trials; Clinical application; Challenges in implementation; Consensus recommendations; Infrastructure for regional MRD adoption; and Roadmap for pragmatic trials. RESULTS: A total of 23 position statements were developed, of which all except one achieved strong consensus. The consensus highlighted the need to define minimum analytical performance thresholds for MRD assays, improve standardization of reporting metrics, and clear guidelines for pre-analytical handling. Harmonization of blood sampling timepoints and terminology across clinical trials is also essential to confirm the prognostic value of MRD assays. While current MRD assays demonstrate high specificity and positive predictive value, variable sensitivity precludes routine use for adjuvant therapy de-escalation outside clinical trials. Broader access, sustainable funding, ongoing consensus building and collaborative real-world data generation are also critical to support clinical implementation and adoption. Future clinical trials must account for the distinct biology and changing standards of care associated with different driver genes. CONCLUSION: These consensus recommendations provide a pragmatic framework to guide the responsible integration of MRD testing into clinical research and practice.", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Aaron C.", "last_name": "Tan", "name": null }, { "creator_type": "author", "first_name": "Bin-Chi", "last_name": "Liao", "name": null }, { "creator_type": "author", "first_name": "Molly", "last_name": "Li", "name": null }, { "creator_type": "author", "first_name": "David", "last_name": "Lee", "name": null }, { "creator_type": "author", "first_name": "Yuji", "last_name": "Uehara", "name": null }, { "creator_type": "author", "first_name": "Lucksamon", "last_name": "Thamlikitkul", "name": null }, { "creator_type": "author", "first_name": "Jia-Tao", "last_name": "Zhang", "name": null }, { "creator_type": "author", "first_name": "Meimei", "last_name": "Zheng", "name": null }, { "creator_type": "author", "first_name": "Chee Khoon", "last_name": "Lee", "name": null }, { "creator_type": "author", "first_name": "Nick", "last_name": "Pavlakis", "name": null }, { "creator_type": "author", "first_name": "Thomas", "last_name": "John", "name": null }, { "creator_type": "author", "first_name": "Ross A.", "last_name": "Soo", "name": null }, { "creator_type": "author", "first_name": "Anders", "last_name": "Skanderup", "name": null }, { "creator_type": "author", "first_name": "Pei Jye", "last_name": "Voon", "name": null }, { "creator_type": "author", "first_name": "Beung-Chul", "last_name": "Ahn", "name": null }, { "creator_type": "author", "first_name": "Sehhoon", "last_name": "Park", "name": null }, { "creator_type": "author", "first_name": "Hidetoshi", "last_name": "Hayashi", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Goto", "name": null }, { "creator_type": "author", "first_name": "Hidehito", "last_name": "Horinouchi", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null }, { "creator_type": "author", "first_name": "Thanyanan", "last_name": "Reungwetwattana", "name": null }, { "creator_type": "author", "first_name": "James", "last_name": "Chih-Hsin Yang", "name": null }, { "creator_type": "author", "first_name": "Dong-Wan", "last_name": "Kim", "name": null }, { "creator_type": "author", "first_name": "Tony", "last_name": "Mok", "name": null }, { "creator_type": "author", "first_name": "Daniel S. W.", "last_name": "Tan", "name": null }, { "creator_type": "author", "first_name": "Yi-Long", "last_name": "Wu", "name": null }, { "creator_type": "author", "first_name": "Myung-Ju", "last_name": "Ahn", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.jtho.2026.103696" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "41903701" } }, "mesh": [ { "descriptor": "Carcinoma, Non-Small-Cell Lung", "descriptor_ui": "D002289", "major_topic": true }, { "descriptor": "Circulating Tumor DNA", "descriptor_ui": "D000074141", "major_topic": true }, { "descriptor": "Delphi Technique", "descriptor_ui": "D003697", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Lung Neoplasms", "descriptor_ui": "D008175", "major_topic": true }, { "descriptor": "Neoplasm Staging", "descriptor_ui": "D009367", "major_topic": false }, { "descriptor": "Neoplasm, Residual", "descriptor_ui": "D018365", "major_topic": true } ], "publication": { "conference_name": null, "date": "2026 Mar 26", "date_precision": "day", "issue": "", "normalized_date": "2026-03-26", "pages": "103696", "proceedings_title": null, "publisher": "", "title": "Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer", "volume": "", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "Consensus statement on ctDNA minimal residual disease (MRD) testing in early-stage NSCLC - A Delphi study by the Asian Thoracic Oncology Research Group (ATORG).", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "INTRODUCTION: Small cell lung cancer (SCLC) is an aggressive malignancy with poor prognosis. Tarlatamab, a bispecific T cell engager that targets CD3 and delta-like ligand 3 (DLL3), is the standard of care for patients with previously treated SCLC. However, the mechanisms underlying acquired tarlatamab resistance remain unclear. METHODS: We assessed two patients with extensive-stage SCLC treated with tarlatamab and an anti-programmed cell death protein 1 (PD-1) antibody in a phase 1b clinical trial (jRCT: 2051240045). We analyzed tumor biopsy samples obtained at baseline and at time of progressive disease using multiplexed immunohistochemistry (mIHC). RESULTS: Pathological analysis of post-resistance specimens revealed a phenotypic shift in both cases, characterized by tumor cells with abundant cytoplasm and reduced synaptophysin expression levels. mIHC revealed low DLL3 expression on tumor cells at time of progression. Additionally, exhausted CD8(+) T cells expressing PD-1(+), T-cell immunoreceptor with Ig and ITIM domains (TIGIT), and/or lymphocyte-activation gene 3 (LAG3), and immunosuppressive cells, including cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) regulatory T cells and CD206(+) M2 tumor-associated macrophages, were significantly more abundant in the tumor microenvironment (TME) than that in samples obtained before tarlatamab plus anti- PD1combination therapy. CONCLUSIONS: Acquired resistance to tarlatamab plus anti-PD-1 in SCLC was associated with low DLL3 antigen expression particularly in the setting of phenotypic switch to a non-small cell lung cancer morphology and an increasingly immunosuppressive TME. Therefore, combination strategies that incorporate immune checkpoint blockade or myeloid-targeted therapies may be warranted to enhance treatment outcomes.", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Akito", "last_name": "Fukuda", "name": null }, { "creator_type": "author", "first_name": "Tomoyo", "last_name": "Fukami", "name": null }, { "creator_type": "author", "first_name": "Kotaro", "last_name": "Nomura", "name": null }, { "creator_type": "author", "first_name": "Jumpei", "last_name": "Kashima", "name": null }, { "creator_type": "author", "first_name": "Shogo", "last_name": "Kumagai", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Goto", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Yoshida", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.jtho.2026.103693" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "41903703" } }, "mesh": [ { "descriptor": "Antibodies, Bispecific", "descriptor_ui": "D018033", "major_topic": false }, { "descriptor": "Drug Resistance, Neoplasm", "descriptor_ui": "D019008", "major_topic": true }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Intracellular Signaling Peptides and Proteins", "descriptor_ui": "D047908", "major_topic": true }, { "descriptor": "Lung Neoplasms", "descriptor_ui": "D008175", "major_topic": true }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Membrane Proteins", "descriptor_ui": "D008565", "major_topic": true }, { "descriptor": "Programmed Cell Death 1 Receptor", "descriptor_ui": "D061026", "major_topic": true }, { "descriptor": "Small Cell Lung Carcinoma", "descriptor_ui": "D055752", "major_topic": true }, { "descriptor": "T-Cell Exhaustion", "descriptor_ui": "D000094383", "major_topic": false } ], "publication": { "conference_name": null, "date": "2026 Mar 26", "date_precision": "day", "issue": "", "normalized_date": "2026-03-26", "pages": "103693", "proceedings_title": null, "publisher": "", "title": "Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer", "volume": "", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "Brief Report: Low Delta-like Ligand 3 expression and T Cell Exhaustion Drive Resistance to Tarlatamab combined with anti-PD-1 in Small-Cell Lung Cancer.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "DNA origami technology is a method for designing and constructing nanoscale structures using DNA, and it is being applied across various fields. This technology was advanced by developing the nanospring (NS), a fluorescently visible molecular spring that quantifies forces through its extension and has been used to measure myosin-generated forces. This study aims to measure the force exerted by the kinesin-3 motor protein KIF1A, mutations of which cause KIF1A-associated neurological disorder (KAND) and are associated with reduced force and motility. Unlike kinesin-1, KIF1A detaches easily under perpendicular loads, which can occur in optical tweezers experiments. By applying force parallel to the microtubule using the NS, we were able to precisely measure the stall force even for KAND mutants, for which such measurements are typically challenging. This result highlights the potential of the NS as a new tool for force spectroscopy in biophysics.", "classifications": [ { "id": "JPMJCR2023", "label": "JPMJCR2023", "researcher": "Fumiko Toyoshima", "type": "grant" }, { "id": "Toyoshima", "label": "Group Toyoshima", "parent": "Toyoshima", "type": "group" }, { "id": "Toyoshima", "label": "Team Toyoshima", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Nobumichi", "last_name": "Takamatsu", "name": null }, { "creator_type": "author", "first_name": "Hiroko", "last_name": "Furumoto", "name": null }, { "creator_type": "author", "first_name": "Takayuki", "last_name": "Ariga", "name": null }, { "creator_type": "author", "first_name": "Mitsuhiro", "last_name": "Iwaki", "name": null }, { "creator_type": "author", "first_name": "Kumiko", "last_name": "Hayashi", "name": null } ], "identifiers": { "doi": { "normalized": "10.7554/elife.108477" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "41879504" } }, "mesh": [ { "descriptor": "DNA", "descriptor_ui": "D004247", "major_topic": true }, { "descriptor": "DNA Nanostructures", "descriptor_ui": "D000099139", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Kinesins", "descriptor_ui": "D016547", "major_topic": true } ], "publication": { "conference_name": null, "date": "2026 Mar 25", "date_precision": "day", "issue": "", "normalized_date": "2026-03-25", "pages": "RP108477", "proceedings_title": null, "publisher": "", "title": "eLife", "volume": "14", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "Stall force measurement of the kinesin-3 motor KIF1A using a programmable DNA origami nanospring.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Phosphoinositides coordinate membrane trafficking and bioenergetic homeostasis, and many tumors rely on elevated phosphoinositide flux to sustain growth. Therapeutic development has largely pursued single-phosphoinositide kinase inhibition, whereas polypharmacologic strategies that perturb the broader network remain underexplored. FTY720 (fingolimod), a clinically approved sphingosine-1-phosphate receptor modulator, shows anti-tumor activity at micromolar concentrations, but its non-canonical mechanisms remain incompletely defined. Building on our work with the structurally related compound KRP203, we show that high-dose FTY720 produces isozyme-divergent modulation across phosphoinositide kinases and biases PIKFYVE activity toward phosphatidylinositol, a pattern we term ASURA (Asymmetric Simultaneous Uncoupling of Related Activities). FTY720 induces vacuolization and endomembrane remodeling in cancer cells, and suppresses macropinocytic ruffling as demonstrated by tracer uptake and scanning ion conductance microscopy analyses. Quantitative metabolomics revealed depletion of intracellular amino acids and ribonucleoside triphosphates, coupled with reduced glycolysis. Concurrently, FTY720 induced extensive rewiring of the hexosamine pathway, nitrogen metabolism, and tricarboxylic acid (TCA)-cycle anaplerosis, along with redox signatures indicating oxidative stress despite a nutrient-replete medium. The metabolites depleted by FTY720 showed extensive, directionally concordant overlap with those depleted by PTEN induction. Patient-derived glioblastoma (GBM) neurospheres were sensitive to FTY720, and co-treatment with a PI3Kalpha-selective inhibitor augmented growth suppression in U87MG cells. Together, these data support a model in which ASURA-dose FTY720 disrupts phosphoinositide-regulated trafficking and nutrient access, imposing intracellular nutrient stress that culminates in tumor-cell death.", "classifications": [ { "id": "JPMJCR2123", "label": "JPMJCR2123", "researcher": "Shinya Kuroda", "type": "grant" }, { "id": "Kuroda", "label": "Group Kuroda", "parent": "Kuroda", "type": "group" }, { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Satoshi", "last_name": "Kofuji", "name": null }, { "creator_type": "author", "first_name": "Kazutaka", "last_name": "Sumita", "name": null }, { "creator_type": "author", "first_name": "Yoshiki", "last_name": "Ikeda", "name": null }, { "creator_type": "author", "first_name": "Yasufumi", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Sho", "last_name": "Tabata", "name": null }, { "creator_type": "author", "first_name": "Doshun", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Yoshihisa", "last_name": "Hirota", "name": null }, { "creator_type": "author", "first_name": "Mika", "last_name": "Sasaki", "name": null }, { "creator_type": "author", "first_name": "Hirotaka", "last_name": "Kanoh", "name": null }, { "creator_type": "author", "first_name": "Fubito", "last_name": "Nakatsu", "name": null }, { "creator_type": "author", "first_name": "Koh", "last_name": "Takeuchi", "name": null }, { "creator_type": "author", "first_name": "Toshiya", "last_name": "Senda", "name": null }, { "creator_type": "author", "first_name": "Mindy I.", "last_name": "Davis", "name": null }, { "creator_type": "author", "first_name": "Min", "last_name": "Shen", "name": null }, { "creator_type": "author", "first_name": "Hiroaki", "last_name": "Wakimoto", "name": null }, { "creator_type": "author", "first_name": "Akiyoshi", "last_name": "Hirayama", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Anton", "last_name": "Simeonov", "name": null }, { "creator_type": "author", "first_name": "Atsuo T.", "last_name": "Sasaki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.bbrc.2026.153671" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "41924780" } }, "mesh": [ { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Fingolimod Hydrochloride", "descriptor_ui": "D000068876", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Phosphatidylinositol 3-Kinases", "descriptor_ui": "D019869", "major_topic": false }, { "descriptor": "Phosphatidylinositols", "descriptor_ui": "D010716", "major_topic": true }, { "descriptor": "Sphingosine 1 Phosphate Receptor Modulators", "descriptor_ui": "D000081243", "major_topic": true } ], "publication": { "conference_name": null, "date": "2026 Mar 24", "date_precision": "day", "issue": "", "normalized_date": "2026-03-24", "pages": "153671", "proceedings_title": null, "publisher": "", "title": "Biochemical and biophysical research communications", "volume": "815", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "Polypharmacologic phosphoinositide modulation by FTY720 triggers endomembrane trafficking collapse and metabolic starvation in cancer cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "", "classifications": [ { "id": "Akaike", "label": "Group Akaike", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Takaaki", "last_name": "Akaike", "name": null }, { "creator_type": "author", "first_name": "Beatriz", "last_name": "Alvarez", "name": null }, { "creator_type": "author", "first_name": "Ruma", "last_name": "Banerjee", "name": null }, { "creator_type": "author", "first_name": "Clive Yik-Sham", "last_name": "Chung", "name": null }, { "creator_type": "author", "first_name": "Tobias P.", "last_name": "Dick", "name": null }, { "creator_type": "author", "first_name": "Cristina", "last_name": "Furdui", "name": null }, { "creator_type": "author", "first_name": "Mark", "last_name": "Hampton", "name": null }, { "creator_type": "author", "first_name": "Elena", "last_name": "Hidalgo", "name": null }, { "creator_type": "author", "first_name": "Gerta", "last_name": "Hoxhaj", "name": null }, { "creator_type": "author", "first_name": "Carola", "last_name": "Neumann", "name": null }, { "creator_type": "author", "first_name": "Pablo", "last_name": "Rivera-Fuentes", "name": null }, { "creator_type": "author", "first_name": "Eranthie", "last_name": "Weerapana", "name": null }, { "creator_type": "author", "first_name": "Ming", "last_name": "Xian", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41589-026-02178-1" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "41876786" } }, "mesh": [], "publication": { "conference_name": null, "date": "2026 Mar 24", "date_precision": "day", "issue": "", "normalized_date": "2026-03-24", "pages": "", "proceedings_title": null, "publisher": "", "title": "Nature chemical biology", "volume": "", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "Frontiers of redox biology.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Actin filaments are essential for plant cellular functions, and their dynamics are altered in response to fungal infection, contributing to defense responses. However, the mechanisms by which pathogens suppress actin-mediated immunity remain largely unknown. Here, we report that infection by the adapted fungus Colletotrichum higginsianum induces actin fragmentation in Arabidopsis thaliana leaf cells. Imaging analyses revealed that actin fragmentation with increased apparent actin thickness occurred following C. higginsianum inoculation. Actin fragmentation was observed two days after inoculation, preceding hyphal invasion on day three. Rhodamine-phalloidin staining confirmed that endogenous actin filaments were disrupted in infected cells. Pretreatment with latrunculin B, which induces actin fragmentation, significantly increased the rate of C. higginsianum hyphal invasion, suggesting that fragmented actin filaments may facilitate fungal entry. Notably, actin fragmentation occurred even in pattern recognition receptor mutants, indicating that it is not triggered by pathogen-associated molecular patterns (PAMP) perception. No obvious changes in microtubule organization were observed. Inoculation with the non-adapted C. tropicale did not induce actin fragmentation in A. thaliana. In contrast, C. higginsianum induced actin fragmentation in cucumber and Brassica crops, whereas C. orbiculare did not, despite being pathogenic to cucumber. These findings suggest that C. higginsianum employs a distinctive infection strategy involving actin fragmentation that is independent of canonical immune recognition.", "classifications": [ { "id": "Higaki", "label": "Group Higaki", "parent": "Ueda", "type": "group" }, { "id": "Ueda", "label": "Team Ueda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Takashi L.", "last_name": "Shimada", "name": null }, { "creator_type": "author", "first_name": "Takumi", "last_name": "Higaki", "name": null }, { "creator_type": "author", "first_name": "Kazuo", "last_name": "Ebine", "name": null }, { "creator_type": "author", "first_name": "Yoshitaka", "last_name": "Takano", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Saijo", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Ueda", "name": null } ], "identifiers": { "doi": { "normalized": "10.1093/pcp/pcag038" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "41870504" } }, "mesh": [ { "descriptor": "Actin Cytoskeleton", "descriptor_ui": "D008841", "major_topic": false }, { "descriptor": "Actins", "descriptor_ui": "D000199", "major_topic": true }, { "descriptor": "Arabidopsis", "descriptor_ui": "D017360", "major_topic": true }, { "descriptor": "Arabidopsis Proteins", "descriptor_ui": "D029681", "major_topic": false }, { "descriptor": "Bridged Bicyclo Compounds, Heterocyclic", "descriptor_ui": "D019086", "major_topic": false }, { "descriptor": "Colletotrichum", "descriptor_ui": "D020231", "major_topic": true }, { "descriptor": "Host-Pathogen Interactions", "descriptor_ui": "D054884", "major_topic": false }, { "descriptor": "Hyphae", "descriptor_ui": "D025301", "major_topic": true }, { "descriptor": "Microtubules", "descriptor_ui": "D008870", "major_topic": false }, { "descriptor": "Plant Diseases", "descriptor_ui": "D010935", "major_topic": true }, { "descriptor": "Plant Leaves", "descriptor_ui": "D018515", "major_topic": true }, { "descriptor": "Thiazolidines", "descriptor_ui": "D053778", "major_topic": false } ], "publication": { "conference_name": null, "date": "2026 Mar 23", "date_precision": "day", "issue": "", "normalized_date": "2026-03-23", "pages": "pcag038", "proceedings_title": null, "publisher": "", "title": "Plant & cell physiology", "volume": "", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "Actin fragmentation induced by Colletotrichum higginsianum infection facilitates hyphal invasion in Arabidopsis thaliana leaves.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Mesenchymal stem/stromal cells (MSCs) are notable for their differentiation potential and immunomodulatory properties. They share several features with macrophages as well as fibrocytes. This study aimed to investigate the relationship between MSCs, fibrocytes, and macrophages, focusing on the hypothesis of a possible direct lineage. Particularly, the focus lies on a freshly isolated murine MSC population known as PαS cells, which were transplanted into irradiated recipients, resulting in cells expressing a macrophage-like phenotype with CD45, CD68, and CSF1R (also known as CD115) expression. Further analysis showed that PαS cells cultured in macrophage differentiation media acquired characteristics of M2 macrophages (CD45, CD68, and CD206) through interaction with CSF1R. These results were confirmed in several mouse strains and human MSCs. Single-cell RNA sequencing revealed macrophage-like populations among the PαS cells, demonstrating the phenotypic plasticity of non-cultured MSCs, giving into MSC potential roles in immune regulation and tissue repair.", "classifications": [ { "id": "JPMJCR2124", "label": "JPMJCR2124", "researcher": "Hirofumi Shintaku", "type": "grant" }, { "id": "Shintaku", "label": "Group Shintaku", "parent": "Shintaku", "type": "group" }, { "id": "Shintaku", "label": "Team Shintaku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Robert M.", "last_name": "Rusch", "name": null }, { "creator_type": "author", "first_name": "Yo", "last_name": "Mabuchi", "name": null }, { "creator_type": "author", "first_name": "Satoru", "last_name": "Morikawa", "name": null }, { "creator_type": "author", "first_name": "Yoko", "last_name": "Ogawa", "name": null }, { "creator_type": "author", "first_name": "Shigeto", "last_name": "Shimmura", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.isci.2026.114906" }, "pmcid": { "normalized": "PMC12936835" }, "pmid": { "normalized": "41767265" } }, "mesh": [], "publication": { "conference_name": null, "date": "2026 Mar 20", "date_precision": "day", "issue": "3", "normalized_date": "2026-03-20", "pages": "114906", "proceedings_title": null, "publisher": "", "title": "iScience", "volume": "29", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "Differentiation of mesenchymal stem/stromal cells into CD45(+) macrophage-like cells: expanding insights into MSC plasticity.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Multiciliated cells (MCCs) are pivotal in airway defense via their motile cilia to eliminate inhaled pathogens and particles. Genetic variants in primary ciliary dyskinesia (PCD) disrupt ciliary function, resulting in chronic respiratory infections. The formation of MCCs requires centriole amplification mediated by non-membranous organelles called deuterosomes, whose regulatory mechanisms remain poorly characterized in humans. Single-cell transcriptomic analyses have identified \"deuterosomal cells\" (DCs), a transient cell population that emerges during multiciliogenesis. DCs are challenging to investigate owing to their scarcity. To elucidate the role of DCs, iPSC-derived airway epithelial cells were used to identify CD36 as a specific surface marker. Furthermore, iPSCs were established from a patient with PCD harboring Cyclin O (CCNO) variants, along with gene-corrected controls. Patient-derived iPSCs demonstrated defective MCC differentiation and aberrant DCs attributed to CCNO deficiency. This study provides a human iPSC-based platform for investigating the mechanisms underlying airway multiciliogenesis and PCD modeling.", "classifications": [ { "id": "Yamamoto", "label": "Group Yamamoto", "parent": "Toyoshima", "type": "group" }, { "id": "Toyoshima", "label": "Team Toyoshima", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Haruka", "last_name": "Yamaki", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Konishi", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Tamai", "name": null }, { "creator_type": "author", "first_name": "Naoyuki", "last_name": "Sone", "name": null }, { "creator_type": "author", "first_name": "Senye", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Yifei", "last_name": "Xu", "name": null }, { "creator_type": "author", "first_name": "Takahiro", "last_name": "Tsuji", "name": null }, { "creator_type": "author", "first_name": "Hiroaki", "last_name": "Ozasa", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Toyohiro", "last_name": "Hirai", "name": null }, { "creator_type": "author", "first_name": "Kazuhiko", "last_name": "Takeuchi", "name": null }, { "creator_type": "author", "first_name": "Shimpei", "last_name": "Gotoh", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.stemcr.2026.102860" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "41861821" } }, "mesh": [ { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": true }, { "descriptor": "Cell Lineage", "descriptor_ui": "D019070", "major_topic": true }, { "descriptor": "Cilia", "descriptor_ui": "D002923", "major_topic": true }, { "descriptor": "Epithelial Cells", "descriptor_ui": "D004847", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Induced Pluripotent Stem Cells", "descriptor_ui": "D057026", "major_topic": false } ], "publication": { "conference_name": null, "date": "2026 Mar 19", "date_precision": "day", "issue": "", "normalized_date": "2026-03-19", "pages": "102860", "proceedings_title": null, "publisher": "", "title": "Stem cell reports", "volume": "", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "Deuterosomal cells are the responsible lineage for multiciliogenesis in human airway differentiation.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The threat of antimicrobial resistance in aquatic environments, particularly riverine systems, is escalating, in part due to effluents discharged from healthcare facilities. This issue has been recognized not only in Japan but also in other Asian countries such as Indonesia and Nepal. Nevertheless, existing research remains limited, prompting an investigation into the prevalence of antimicrobial-resistant bacteria in the upstream and downstream sites of environmental rivers. In 2024, six samples were collected from three rivers in Hyogo Prefecture, Japan; five samples from five river sites in Indonesia; and three samples from downstream sites of rivers in Kathmandu, Nepal. These samples were subjected to selective culture-based Next Generation Sequencing and resistome analyses, based exclusively on the selective culture of bacteria propagated on CHROMagar ESBL plates. In Japan and Indonesia, Pseudomonas, Stenotrophomonas and Acinetobacter were frequently detected, whereas Klebsiella was overwhelmingly predominant in Nepal. Significant differences in the similarity of bacterial community composition among sampling sites across the three countries were observed (p < 0.001). Notably, Nepal exhibited the highest abundance level of antimicrobial resistance genes among the three countries, largely consisting of β-lactam resistance genes. In conclusion, these analyses elucidated substantial differences in bacterial community composition and degrees of environmental contamination.", "classifications": [ { "id": "Suzuki", "label": "Group Suzuki", "parent": "Takekawa", "type": "group" }, { "id": "Takekawa", "label": "Team Takekawa", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Kayo", "last_name": "Osawa", "name": null }, { "creator_type": "author", "first_name": "Ryohei", "last_name": "Nomoto", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Taishi", "last_name": "Maeda", "name": null }, { "creator_type": "author", "first_name": "Ganesh", "last_name": "Rai", "name": null }, { "creator_type": "author", "first_name": "Shouhiro", "last_name": "Kinoshita", "name": null }, { "creator_type": "author", "first_name": "Noriko", "last_name": "Nakanishi", "name": null }, { "creator_type": "author", "first_name": "Dadik", "last_name": "Raharjo", "name": null }, { "creator_type": "author", "first_name": "Masanori", "last_name": "Kameoka", "name": null }, { "creator_type": "author", "first_name": "Masato", "last_name": "Fujisawa", "name": null }, { "creator_type": "author", "first_name": "Shiba Kumar", "last_name": "Rai", "name": null }, { "creator_type": "author", "first_name": "Kuntaman", "last_name": "Kuntaman", "name": null }, { "creator_type": "author", "first_name": "Toshiro", "last_name": "Shirakawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.3390/pathogens15030317" }, "pmcid": { "normalized": "PMC13028957" }, "pmid": { "normalized": "41901770" } }, "mesh": [ { "descriptor": "Bacteria", "descriptor_ui": "D001419", "major_topic": true }, { "descriptor": "Drug Resistance, Bacterial", "descriptor_ui": "D024881", "major_topic": true }, { "descriptor": "Health Facilities", "descriptor_ui": "D006268", "major_topic": false }, { "descriptor": "Indonesia", "descriptor_ui": "D007214", "major_topic": false }, { "descriptor": "Japan", "descriptor_ui": "D007564", "major_topic": false }, { "descriptor": "Medical Waste Disposal", "descriptor_ui": "D017744", "major_topic": true }, { "descriptor": "Nepal", "descriptor_ui": "D009390", "major_topic": false }, { "descriptor": "Rivers", "descriptor_ui": "D045483", "major_topic": true } ], "publication": { "conference_name": null, "date": "2026 Mar 15", "date_precision": "day", "issue": "3", "normalized_date": "2026-03-15", "pages": "", "proceedings_title": null, "publisher": "", "title": "Pathogens (Basel, Switzerland)", "volume": "15", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "Survey of Antimicrobial-Resistant Bacteria Isolated from Rivers in Japan, Indonesia and Nepal.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: Early detection of metabolic dysfunction before diabetes onset remains a critical challenge in preventive medicine. Although glucose dynamics provide high-dimensional insights into metabolic states, it remains unclear which combination of glucose dynamics-derived measures most effectively summarises interindividual differences in glucose regulation. METHODS: We analysed continuous glucose monitoring (CGM) data from 8025 adults without diagnosed diabetes, using all recordings of at least seven days' duration, to derive a low-dimensional representation of glucose dynamics. Using exploratory factor analysis, we identified a small set of latent features that accounted for variation between individuals in CGM-derived metrics. We then trained and validated machine-learning models to predict postprandial glucose trajectories from these features in 863 participants who underwent standardised meal tests. We further assessed the generalisability of this representation in an independent oral glucose tolerance test dataset. Finally, we examined associations between the derived features and markers of vascular and liver health in 1784 non-diabetic adults. RESULTS: Three features, \"mean\", \"variance\", and \"autocorrelation\", explain more than 80% of the interindividual differences in CGM-derived measures. A three-dimensional representation based on these features reconstructs postprandial glucose trajectories with high accuracy and outperforms fasting, mean, and two-hour postprandial glucose values. Each feature shows independent associations with carotid artery intima-media thickness and with hepatic steatosis and stiffness. CONCLUSIONS: By compressing high-dimensional glucose dynamics into three interpretable features with minimal loss of information, this framework provides a simple yet physiologically meaningful representation of glucose regulation that may facilitate a more precise and interpretable assessment of diabetes-related risk.", "classifications": [ { "id": "JPMJCR2123", "label": "JPMJCR2123", "researcher": "Shinya Kuroda", "type": "grant" }, { "id": "Kuroda", "label": "Group Kuroda", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Hikaru", "last_name": "Sugimoto", "name": null }, { "creator_type": "author", "first_name": "Gal", "last_name": "Sapir", "name": null }, { "creator_type": "author", "first_name": "Ayya", "last_name": "Keshet", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Kuroda", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s43856-026-01523-8" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "41832215" } }, "mesh": [], "publication": { "conference_name": null, "date": "2026 Mar 14", "date_precision": "day", "issue": "", "normalized_date": "2026-03-14", "pages": "", "proceedings_title": null, "publisher": "", "title": "Communications medicine", "volume": "", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "Use of continuous glucose monitoring to stratify individuals without diabetes.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Mutual information is a theoretically grounded metric for quantifying cellular signaling pathways. However, its measurement demands characterization of both input and output distributions, limiting practical applications. Here, we present alternative method that alleviates this requirement using dual reporter systems. By extending extrinsic-intrinsic noise analysis, we derive a mutual information estimator that eliminates the need to measure input distribution. We demonstrate our method by analyzing the bacterial chemotactic pathway, regarding multiple flagellar motors as natural dual reporters. We show the biological relevance of the measured information flow by comparing it with theoretical bounds on sensory information. This framework opens new directions for quantifying information flow in cellular signaling pathways.", "classifications": [ { "id": "Kobayashi", "label": "Group Kobayashi", "parent": "Wakamoto", "type": "group" }, { "id": "Wakamoto", "label": "Team Wakamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Kento", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Hajime", "last_name": "Fukuoka", "name": null }, { "creator_type": "author", "first_name": "Akihiko", "last_name": "Ishijima", "name": null }, { "creator_type": "author", "first_name": "Tetsuya J.", "last_name": "Kobayashi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1103/jrph-wj94" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "41894793" } }, "mesh": [ { "descriptor": "Chemotaxis", "descriptor_ui": "D002633", "major_topic": true }, { "descriptor": "Escherichia coli", "descriptor_ui": "D004926", "major_topic": false }, { "descriptor": "Flagella", "descriptor_ui": "D005407", "major_topic": false }, { "descriptor": "Models, Biological", "descriptor_ui": "D008954", "major_topic": true }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false } ], "publication": { "conference_name": null, "date": "2026 Mar 13", "date_precision": "day", "issue": "10", "normalized_date": "2026-03-13", "pages": "108403", "proceedings_title": null, "publisher": "", "title": "Physical review letters", "volume": "136", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "Quantification of Information Flow by Dual Reporter System and Its Application to Bacterial Chemotaxis.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Tissue clearing has been widely used for fluorescence imaging of fixed tissues, but its application to live tissues has been limited by toxicity. Here we develop minimally invasive optical clearing media for fluorescence imaging of live mammalian tissues. Light scattering is minimized by adding spherical polymers with low osmolarity to the extracellular medium. A clearing medium containing bovine serum albumin (SeeDB-Live) is compatible with live cells, enabling structural and functional imaging of live tissues, such as spheroids, organoids, acute brain slices and the mouse brains in vivo. SeeDB-Live minimally affects neuronal electrophysiological properties and sensory responses in vivo, and facilitates fluorescence imaging of deep cortical layers in live animals without detectable toxicity to neurons or behavior. We further demonstrate its utility to epifluorescence voltage imaging in acute brain slices and in vivo preparations. Thus, SeeDB-Live expands both the depth and modality range of fluorescence imaging in live mammalian tissues.", "classifications": [ { "id": "JPMJCR2021", "label": "JPMJCR2021", "researcher": "Hideki Enomoto", "type": "grant" }, { "id": "Enomoto", "label": "Group Enomoto", "parent": "Enomoto", "type": "group" }, { "id": "Imai", "label": "Group Imai", "parent": "Enomoto", "type": "group" }, { "id": "Okuda", "label": "Group Okuda", "parent": "Imayoshi", "type": "group" }, { "id": "Enomoto", "label": "Team Enomoto", "type": "team" }, { "id": "Imayoshi", "label": "Team Imayoshi", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Shigenori", "last_name": "Inagaki", "name": null }, { "creator_type": "author", "first_name": "Nao", "last_name": "Nakagawa-Tamagawa", "name": null }, { "creator_type": "author", "first_name": "Nathan Zechen", "last_name": "Huynh", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Kambe", "name": null }, { "creator_type": "author", "first_name": "Rei", "last_name": "Yagasaki", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Manita", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Fujimoto", "name": null }, { "creator_type": "author", "first_name": "Takahiro", "last_name": "Noda", "name": null }, { "creator_type": "author", "first_name": "Misato", "last_name": "Mori", "name": null }, { "creator_type": "author", "first_name": "Aki", "last_name": "Teranishi", "name": null }, { "creator_type": "author", "first_name": "Hikari", "last_name": "Takeshima", "name": null }, { "creator_type": "author", "first_name": "Koki", "last_name": "Ishikawa", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Naitou", "name": null }, { "creator_type": "author", "first_name": "Tatsushi", "last_name": "Yokoyama", "name": null }, { "creator_type": "author", "first_name": "Masayuki", "last_name": "Sakamoto", "name": null }, { "creator_type": "author", "first_name": "Katsuhiko", "last_name": "Hayashi", "name": null }, { "creator_type": "author", "first_name": "Kazuo", "last_name": "Kitamura", "name": null }, { "creator_type": "author", "first_name": "Yoshiaki", "last_name": "Tagawa", "name": null }, { "creator_type": "author", "first_name": "Satoru", "last_name": "Okuda", "name": null }, { "creator_type": "author", "first_name": "Tatsuo K.", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Imai", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41592-026-03023-y" }, "pmcid": { "normalized": null }, "pmid": { "normalized": null } }, "mesh": [], "publication": { "conference_name": null, "date": "2026-03-12", "date_precision": "day", "issue": "", "normalized_date": "2026-03-12", "pages": "1-15", "proceedings_title": null, "publisher": "Nature Publishing Group", "title": "Nature Methods", "volume": "", "year": 2026 }, "ssbd": { "database": [ "ssbd-database-000484" ], "repository": [ "ssbd-repos-000484" ] }, "title": "Isotonic and minimally invasive optical clearing media for live cell imaging ex vivo and in vivo", "url": "https://www.nature.com/articles/s41592-026-03023-y", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Uterine serous carcinoma (USC) is an aggressive p53-mutated endometrial carcinoma that exhibits gene mutations in homologous recombination (HR) pathways, similar to high-grade serous ovarian carcinoma (HGSOC). However, the therapeutic effect of PARP inhibitors on USC is limited. This study investigated cyclin-dependent kinase 12 (CDK12), a transcriptional regulator of HR genes, and evaluated the efficacy of a novel CDK12 inhibitor, CTX-439, combined with a PARP inhibitor, olaparib, in patient-derived xenograft (PDX) models of USC. We evaluated the homologous recombination deficiency (HRD) scores, genetic alterations, and HR-related gene abnormalities, including CDK12 in USC, other histopathological types of uterine endometrial carcinoma, and HGSOC using the Cancer Genome Atlas dataset. We also assessed CDK12 function and CTX-439 efficacy in USC utilizing USC cell lines and PDX models. USC exhibited a higher HRD score than other histological subtypes of uterine endometrial carcinoma but lower than HGSOC. CDK12 amplification occurred more frequently in USC than in HGSOC but was not associated with HRD scores. Tumors with CDK12 amplification demonstrated high CDK12 expression, which correlated with poor prognosis in USC. The CDK12 inhibitor CTX-439 suppressed HR-related gene expression, including BRCA1 and BRCA2, induced apoptosis and DNA damage, and inhibited tumor growth in USC PDX models with high CDK12 expression. Furthermore, CDK12 inhibition enhanced tumor sensitivity to the PARP inhibitor, olaparib in USC PDX models. This study indicates that CDK12 is a potential therapeutic target for enhancing the antitumor effects of PARP inhibitors in patients with USC.", "classifications": [ { "id": "Yusa", "label": "Group Yusa", "parent": "Eiraku", "type": "group" }, { "id": "Eiraku", "label": "Team Eiraku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Shunsuke", "last_name": "Kawahara", "name": null }, { "creator_type": "author", "first_name": "Mana", "last_name": "Taki", "name": null }, { "creator_type": "author", "first_name": "Junzo", "last_name": "Hamanishi", "name": null }, { "creator_type": "author", "first_name": "Shunsuke", "last_name": "Ebara", "name": null }, { "creator_type": "author", "first_name": "Ryusuke", "last_name": "Murakami", "name": null }, { "creator_type": "author", "first_name": "Kohei", "last_name": "Hamada", "name": null }, { "creator_type": "author", "first_name": "Koichi", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Yuko", "last_name": "Hosoe", "name": null }, { "creator_type": "author", "first_name": "Yuka", "last_name": "Mise", "name": null }, { "creator_type": "author", "first_name": "Shiro", "last_name": "Takamatsu", "name": null }, { "creator_type": "author", "first_name": "Taito", "last_name": "Miyamoto", "name": null }, { "creator_type": "author", "first_name": "Rin", "last_name": "Mizuno", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Yamanoi", "name": null }, { "creator_type": "author", "first_name": "Ken", "last_name": "Yamaguchi", "name": null }, { "creator_type": "author", "first_name": "Hiroko", "last_name": "Yamakawa", "name": null }, { "creator_type": "author", "first_name": "Nobuyuki", "last_name": "Kakiuchi", "name": null }, { "creator_type": "author", "first_name": "Tsukasa", "last_name": "Baba", "name": null }, { "creator_type": "author", "first_name": "Seishi", "last_name": "Ogawa", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Morishita", "name": null }, { "creator_type": "author", "first_name": "Kosuke", "last_name": "Yusa", "name": null }, { "creator_type": "author", "first_name": "Masaki", "last_name": "Mandai", "name": null } ], "identifiers": { "doi": { "normalized": "10.1158/1535-7163.mct-25-0954" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "41814851" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Cyclin-Dependent Kinases", "descriptor_ui": "D018844", "major_topic": true }, { "descriptor": "Cystadenocarcinoma, Serous", "descriptor_ui": "D018284", "major_topic": true }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Homologous Recombination", "descriptor_ui": "D059765", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Phthalazines", "descriptor_ui": "D010793", "major_topic": false }, { "descriptor": "Piperazines", "descriptor_ui": "D010879", "major_topic": false }, { "descriptor": "Poly(ADP-ribose) Polymerase Inhibitors", "descriptor_ui": "D000067856", "major_topic": true }, { "descriptor": "Uterine Neoplasms", "descriptor_ui": "D014594", "major_topic": true }, { "descriptor": "Xenograft Model Antitumor Assays", "descriptor_ui": "D023041", "major_topic": false } ], "publication": { "conference_name": null, "date": "2026 Mar 12", "date_precision": "day", "issue": "", "normalized_date": "2026-03-12", "pages": "", "proceedings_title": null, "publisher": "", "title": "Molecular cancer therapeutics", "volume": "", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "A novel CDK12 inhibitor induces homologous recombination deficiency to enhance PARP inhibitor efficacy in uterine serous carcinoma.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Hikaru", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Hideki", "last_name": "Makinoshima", "name": null }, { "creator_type": "author", "first_name": "Naoki", "last_name": "Kanauchi", "name": null }, { "creator_type": "author", "first_name": "Takanobu", "last_name": "Kabasawa", "name": null }, { "creator_type": "author", "first_name": "Jun", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Takamori", "name": null }, { "creator_type": "author", "first_name": "Takayuki", "last_name": "Sasage", "name": null }, { "creator_type": "author", "first_name": "Kohei", "last_name": "Abe", "name": null }, { "creator_type": "author", "first_name": "Kazumasa", "last_name": "Hoshijima", "name": null }, { "creator_type": "author", "first_name": "Tetsuro", "last_name": "Uchida", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Shiono", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/s00595-026-03276-2" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "41806212" } }, "mesh": [], "publication": { "conference_name": null, "date": "2026 Mar 10", "date_precision": "day", "issue": "", "normalized_date": "2026-03-10", "pages": "", "proceedings_title": null, "publisher": "", "title": "Surgery today", "volume": "", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "Elevated glucose metabolism via the hexosamine biosynthesis pathway: A metabolic signature of high-fluorodeoxyglucose-uptake lung adenocarcinoma.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "", "classifications": [ { "id": "Ueda", "label": "Group Ueda", "parent": "Ueda", "type": "group" }, { "id": "Ueda", "label": "Team Ueda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Hidemasa", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Minako", "last_name": "Ueda", "name": null } ], "identifiers": { "doi": { "normalized": "10.1093/pcp/pcag029" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "41786637" } }, "mesh": [], "publication": { "conference_name": null, "date": "2026 Mar 6", "date_precision": "day", "issue": "", "normalized_date": "2026-03-06", "pages": "pcag029", "proceedings_title": null, "publisher": "", "title": "Plant & cell physiology", "volume": "", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "Plant embryogenesis: plasticity and robustness through a 3D lens.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The mechanism underlying retinal spheroid layer formation was investigated using Rax::GFP-positive retinal progenitor cells from human embryonic stem cell-derived retinal organoids. Single-cell RNA sequencing suggested the earlier cell-cycle exit in non-layered spheroids, while well-layered spheroids retained longer proliferative property with transiently activated canonical WNT2B-FZD7 signaling followed by temporary expression of non-canonical WNT5A. Despite structural differences in vitro, however, both non-layered and well-layered retinal spheroids on differentiation day 60 developed a layer of photoreceptors after transplantation in a retinal degeneration rat model, resulting in synaptic and functional integration. Additionally, part of the Rax::GFP-positive cells differentiated into non-retinal lineages, including ciliary marginal zone-like, retinal pigment epithelium, and spinal cord-like tissues in vitro, reflecting the heterogeneity of RAX-positive cells. These findings suggest that canonical and non-canonical WNT signaling pathways sequentially orchestrate early retinal morphogenesis, whereas environmental factors within the host retina strongly drive the alignment and functional integration of graft photoreceptors.", "classifications": [ { "id": "JPMJCR1926", "label": "JPMJCR1926", "researcher": "Hironobu Fujiwara", "type": "grant" }, { "id": "Fujiwara", "label": "Group Fujiwara", "parent": "Fujiwara", "type": "group" }, { "id": "Nikaido", "label": "Group Nikaido", "parent": "Fujiwara", "type": "group" }, { "id": "Fujiwara", "label": "Team Fujiwara", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yasuaki", "last_name": "Iwama", "name": null }, { "creator_type": "author", "first_name": "Tomohiro", "last_name": "Masuda", "name": null }, { "creator_type": "author", "first_name": "Mika", "last_name": "Yoshimura", "name": null }, { "creator_type": "author", "first_name": "Mikiya", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Yoko", "last_name": "Ohigashi", "name": null }, { "creator_type": "author", "first_name": "Martin", "last_name": "Friedlander", "name": null }, { "creator_type": "author", "first_name": "Kohji", "last_name": "Nishida", "name": null }, { "creator_type": "author", "first_name": "Masayo", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Itoshi", "last_name": "Nikaido", "name": null }, { "creator_type": "author", "first_name": "Michiko", "last_name": "Mandai", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.stemcr.2026.102831" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "41791386" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Genomics", "descriptor_ui": "D023281", "major_topic": true }, { "descriptor": "Human Embryonic Stem Cells", "descriptor_ui": "D000066449", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Organoids", "descriptor_ui": "D009940", "major_topic": false }, { "descriptor": "Pluripotent Stem Cells", "descriptor_ui": "D039904", "major_topic": true }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Retina", "descriptor_ui": "D012160", "major_topic": true }, { "descriptor": "Retinal Degeneration", "descriptor_ui": "D012162", "major_topic": false }, { "descriptor": "Retinal Pigment Epithelium", "descriptor_ui": "D055213", "major_topic": false }, { "descriptor": "Spheroids, Cellular", "descriptor_ui": "D018874", "major_topic": false }, { "descriptor": "Wnt Signaling Pathway", "descriptor_ui": "D060449", "major_topic": false } ], "publication": { "conference_name": null, "date": "2026 Mar 5", "date_precision": "day", "issue": "", "normalized_date": "2026-03-05", "pages": "102831", "proceedings_title": null, "publisher": "", "title": "Stem cell reports", "volume": "", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "Genomic characterization of sub-populations in human pluripotent stem cell-derived retinal progenitor cells driving retinal lamination.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The clinical application of artificial intelligence (AI) can provide technical support for examiners and improve obstetric workflow efficiency. In this study, we developed AI models that automatically extract the four-chamber view (4CV) from fetal cardiac ultrasound videos and compute the cardiothoracic area ratio, cardiac axis, and cardiac position for prenatal screening of congenital heart disease. Fetal cardiac ultrasound videos from 301 patients in the second trimester were analyzed. The 4CV was automatically extracted using YOLOv7, followed by image segmentation with UNet 3+ and SegFormer, after which automated parameter calculation and estimation were performed. A clinical comparison study involving 22 obstetricians was conducted to evaluate the screening performance of the AI models. The models demonstrated stable performance in both normal and abnormal cases, including examinations acquired using different ultrasound systems. Furthermore, the AI models achieved screening performance comparable to that of expert obstetricians. These findings indicate that the proposed AI framework enables reliable 4CV extraction and accurate biometric parameter computation. This fully automated approach has the potential to reduce missed abnormalities and improve the consistency of fetal cardiac ultrasound screening.", "classifications": [ { "id": "Hamamoto", "label": "Group Hamamoto", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Naoki", "last_name": "Teraya", "name": null }, { "creator_type": "author", "first_name": "Masaaki", "last_name": "Komatsu", "name": null }, { "creator_type": "author", "first_name": "Katsuji", "last_name": "Takeda", "name": null }, { "creator_type": "author", "first_name": "Kanto", "last_name": "Shozu", "name": null }, { "creator_type": "author", "first_name": "Naoaki", "last_name": "Harada", "name": null }, { "creator_type": "author", "first_name": "Reina", "last_name": "Komatsu", "name": null }, { "creator_type": "author", "first_name": "Akira", "last_name": "Sakai", "name": null }, { "creator_type": "author", "first_name": "Rina", "last_name": "Aoyama", "name": null }, { "creator_type": "author", "first_name": "Mayumi", "last_name": "Kaneko", "name": null }, { "creator_type": "author", "first_name": "Ken", "last_name": "Asada", "name": null }, { "creator_type": "author", "first_name": "Syuzo", "last_name": "Kaneko", "name": null }, { "creator_type": "author", "first_name": "Kazuki", "last_name": "Iwamoto", "name": null }, { "creator_type": "author", "first_name": "Akitoshi", "last_name": "Nakashima", "name": null }, { "creator_type": "author", "first_name": "Ryu", "last_name": "Matsuoka", "name": null }, { "creator_type": "author", "first_name": "Akihiko", "last_name": "Sekizawa", "name": null }, { "creator_type": "author", "first_name": "Ryuji", "last_name": "Hamamoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.3390/bioengineering13030303" }, "pmcid": { "normalized": "PMC13023647" }, "pmid": { "normalized": "41899834" } }, "mesh": [], "publication": { "conference_name": null, "date": "2026 Mar 5", "date_precision": "day", "issue": "3", "normalized_date": "2026-03-05", "pages": "", "proceedings_title": null, "publisher": "", "title": "Bioengineering (Basel, Switzerland)", "volume": "13", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "Artificial Intelligence-Based Automated Assessment of the Four-Chamber View in Fetal Cardiac Ultrasound Videos.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "A two-dimensional Kagome-type MOF (Azln-KGM) incorporating 1,3-azulenedicarboxylate ligands was synthesized. Compared with reported isomorphous MOFs featuring a benzene motif, Azln-KGM exhibited an enhanced maximum adsorption capacity and gate-opening behavior accompanied by larger structural changes.", "classifications": [ { "id": "Hijikata", "label": "Group Hijikata", "parent": "Tsuchiya", "type": "group" }, { "id": "Tsuchiya", "label": "Team Tsuchiya", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Teppei", "last_name": "Takahara", "name": null }, { "creator_type": "author", "first_name": "Junichi", "last_name": "Usuba", "name": null }, { "creator_type": "author", "first_name": "Shinpei", "last_name": "Kusaka", "name": null }, { "creator_type": "author", "first_name": "Yuh", "last_name": "Hijikata", "name": null }, { "creator_type": "author", "first_name": "Hiroaki", "last_name": "Iguchi", "name": null }, { "creator_type": "author", "first_name": "Kenichi", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Ryotaro", "last_name": "Matsuda", "name": null } ], "identifiers": { "doi": { "normalized": "10.1039/d6cc00074f" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "41783934" } }, "mesh": [], "publication": { "conference_name": null, "date": "2026 Mar 5", "date_precision": "day", "issue": "", "normalized_date": "2026-03-05", "pages": "", "proceedings_title": null, "publisher": "", "title": "Chemical communications (Cambridge, England)", "volume": "", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "Expansion of pore size and interlayer distance in a Kagome-type MOF engineered through the geometric features of azulene.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Starvation induces complex metabolic adaptations in skeletal muscle, a key tissue for maintaining energy homeostasis; however, these adaptations are largely impaired in obesity. How obesity alters global metabolic adaptations to starvation in skeletal muscle remains unclear. Here, we analyzed the metabolic adaptations on a trans-omics scale during starvation in skeletal muscle from wild-type (WT) and leptin-deficient obese (ob/ob) mice. We measured multi-omics data during starvation and constructed global trans-omics networks in WT and ob/ob mice. We found that starvation induces \"responsiveness\" in WT mice, characterized by increases or decreases in key regulator metabolites, including ATP and AMP, as well as enzyme proteins, leading to global regulation of metabolic pathways, which was lost in ob/ob mice. In contrast, during starvation, ob/ob mice exhibit \"difference\" in comparison to WT mice, manifested by the persistently elevated expression of metabolic enzymes. These features were similarly found in liver, another key metabolic organ. Thus, global loss of responsiveness and elevated enzyme proteins are systemic features of metabolic dysregulation in ob/ob mice.", "classifications": [ { "id": "JPMJCR2123", "label": "JPMJCR2123", "researcher": "Shinya Kuroda", "type": "grant" }, { "id": "Inaba", "label": "Group Inaba", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Group Kuroda", "parent": "Kuroda", "type": "group" }, { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Dongzi", "last_name": "Li", "name": null }, { "creator_type": "author", "first_name": "Keigo", "last_name": "Morita", "name": null }, { "creator_type": "author", "first_name": "Toshiya", "last_name": "Kokaji", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Hatano", "name": null }, { "creator_type": "author", "first_name": "Akiyoshi", "last_name": "Hirayama", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Yutaka", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Masaki", "last_name": "Matsumoto", "name": null }, { "creator_type": "author", "first_name": "Takaho", "last_name": "Tsuchiya", "name": null }, { "creator_type": "author", "first_name": "Haruka", "last_name": "Ozaki", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Ohno", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Inoue", "name": null }, { "creator_type": "author", "first_name": "Yuka", "last_name": "Inaba", "name": null }, { "creator_type": "author", "first_name": "Hideki", "last_name": "Maehara", "name": null }, { "creator_type": "author", "first_name": "Hikaru", "last_name": "Sugimoto", "name": null }, { "creator_type": "author", "first_name": "Yifei", "last_name": "Pan", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Kuroda", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41540-026-00678-3" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "41775704" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Energy Metabolism", "descriptor_ui": "D004734", "major_topic": false }, { "descriptor": "Leptin", "descriptor_ui": "D020738", "major_topic": true }, { "descriptor": "Liver", "descriptor_ui": "D008099", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Metabolic Networks and Pathways", "descriptor_ui": "D053858", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Obese", "descriptor_ui": "D008820", "major_topic": false }, { "descriptor": "Muscle, Skeletal", "descriptor_ui": "D018482", "major_topic": false }, { "descriptor": "Obesity", "descriptor_ui": "D009765", "major_topic": true }, { "descriptor": "Starvation", "descriptor_ui": "D013217", "major_topic": true } ], "publication": { "conference_name": null, "date": "2026 Mar 3", "date_precision": "day", "issue": "", "normalized_date": "2026-03-03", "pages": "", "proceedings_title": null, "publisher": "", "title": "NPJ systems biology and applications", "volume": "", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "Global loss of metabolic responsiveness and elevated enzyme in leptin deficient obese mice during starvation.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Hematological malignancy (HM) is developed in 2-6% patients with primary mediastinal germ cell tumor (MGCT). Symptoms of HM associated with MGCT usually appear after diagnosis of MGCT. Patients with MGCT underlying HM have poor prognosis. We report an extremely rare autopsy case of simultaneous presentation of MGCT, myelodysplastic neoplasm (MDS) with low blasts, and myeloid sarcoma (MS). A 27-year-old man presented with intermittent fever, general fatigue, and cough. Computed tomography revealed 11 cm mass in anterior mediastinum, hepatosplenomegaly, and gastric, pericholedochal, and mesenteric lymphadenopathies. The mass compressed the left pulmonary artery. Laboratory examination revealed thrombocytopenia (59,000 /mm(3)). Serological tests revealed elevated alpha-fetoprotein 7,219 ng/mL and human chorionic gonadotropin 899 IU/L. Bone marrow aspiration smear showed presence of micromegakaryocytes and blast count of 1.2%. G-banding detected monosomy 13 and complex karyotype. The autopsy revealed that MGCT was mainly composed of teratoma and also included yolk sac tumor, seminoma, and choriocarcinoma components. Transformation to acute myeloid leukemia was not observed in the bone marrow but CD33 and MPO-positive immature myeloid blasts proliferated in the lymph nodes, liver, spleen, and small intestine. Loss of p53 expression was observed in bone marrow and extramedullary immature myeloid blasts. Next gene sequencing detected TP53 c.919+3del splice site variant and KRAS N116H. It is important to consider HMs when extramediastinal lesions or thrombocytopenia appear in patients with MGCT.", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yuto", "last_name": "Kaimi", "name": null }, { "creator_type": "author", "first_name": "Toshihiro", "last_name": "Haga", "name": null }, { "creator_type": "author", "first_name": "Yuhei", "last_name": "Yamaguchi", "name": null }, { "creator_type": "author", "first_name": "Kazuki", "last_name": "Sudo", "name": null }, { "creator_type": "author", "first_name": "Kan", "last_name": "Yonemori", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null } ], "identifiers": { "doi": { "normalized": "10.3960/jslrt.25059" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "41765467" } }, "mesh": [ { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Autopsy", "descriptor_ui": "D001344", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mediastinal Neoplasms", "descriptor_ui": "D008479", "major_topic": true }, { "descriptor": "Myelodysplastic Syndromes", "descriptor_ui": "D009190", "major_topic": true }, { "descriptor": "Neoplasms, Germ Cell and Embryonal", "descriptor_ui": "D009373", "major_topic": true }, { "descriptor": "Sarcoma, Myeloid", "descriptor_ui": "D023981", "major_topic": true } ], "publication": { "conference_name": null, "date": "2026 Feb 28", "date_precision": "day", "issue": "", "normalized_date": "2026-02-28", "pages": "", "proceedings_title": null, "publisher": "", "title": "Journal of clinical and experimental hematopathology : JCEH", "volume": "", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "Cooccurrence of myelodysplastic neoplasm and myeloid sarcoma with background mediastinal germ cell tumor: an autopsy case.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Vertebrate embryos vary in size and developmental tempo based on reproductive strategies; however, organs of ancient origin, such as the eye and inner ear, remain highly conserved in structure and function. How both diverse embryonic traits and conserved organ development occur remains unclear. Here, we identify divergent morphogenetic mechanics of inner ear development, particularly in vesicular primordium expansion, in 12 species representing the major vertebrate lineages. Differences in cell volume regulation determine tissue growth mechanics, which diversify the expansion process but yield a conserved morphological outcome. Heterochronic shifts in organogenesis allow this regulation to evolve in coordination with a prolonged developmental period. These findings suggest that alternative morphogenetic mechanics mitigate the effects of diversified embryonic traits, thereby ensuring consistent morphological outcomes for highly conserved organs.", "classifications": [ { "id": "JPMJCR1921", "label": "JPMJCR1921", "researcher": "Itaru Imayoshi", "type": "grant" } ], "creators": [ { "creator_type": "author", "first_name": "Shunya", "last_name": "Kuroda", "name": null }, { "creator_type": "author", "first_name": "Shuhei A.", "last_name": "Horiguchi", "name": null }, { "creator_type": "author", "first_name": "Soichiro", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Oki", "last_name": "Hayasaka", "name": null }, { "creator_type": "author", "first_name": "Hiroyasu", "last_name": "Kamei", "name": null }, { "creator_type": "author", "first_name": "Wataru", "last_name": "Takagi", "name": null }, { "creator_type": "author", "first_name": "Shinnosuke", "last_name": "Higuchi", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Hirasawa", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Fujimura", "name": null }, { "creator_type": "author", "first_name": "Kiyoshi", "last_name": "Hiraoka", "name": null }, { "creator_type": "author", "first_name": "Nanoka", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Hajime", "last_name": "Ogino", "name": null }, { "creator_type": "author", "first_name": "Anna", "last_name": "Yasunaga", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Kiyonari", "name": null }, { "creator_type": "author", "first_name": "Shigeru", "last_name": "Kuratani", "name": null }, { "creator_type": "author", "first_name": "Satoru", "last_name": "Okuda", "name": null } ], "identifiers": { "doi": { "normalized": "10.64898/2026.02.27.706697" }, "pmcid": { "normalized": null }, "pmid": { "normalized": null } }, "mesh": [], "publication": { "conference_name": null, "date": "2026-02-28", "date_precision": "day", "issue": null, "normalized_date": "2026-02-28", "pages": null, "proceedings_title": null, "publisher": null, "title": null, "volume": null, "year": 2026 }, "ssbd": { "database": [], "repository": [ "ssbd-repos-000496" ] }, "title": "Divergent mechanics of inner ear morphogenesis are coupled to developmental tempo over vertebrate evolution", "url": "https://www.biorxiv.org/content/10.64898/2026.02.27.706697v1", "zotero": { "item_type": "preprint" } }, { "abstract": "The heart is a functional syncytium consisting of numerous cardiomyocytes that repetitively exhibit coordinated contractions/relaxations. However, the extent to which myocyte sarcomere arrangements in the heart differ across beats is unknown. To examine this, we conducted cardiac phase-targeting rapid cryofixation of Langendorff-perfused rat hearts. We adjusted the timepoint of cryogen exposure to the electrically paced heart and observed phase-dependent differences in the sarcomere length (SL) of subepicardial myocytes by alpha-actinin immunohistochemistry, namely a significantly shorter SL during systole than during diastole. We detected spatially inhomogeneous SL distributions by generating a heatmap of the myocardium. For peak systole the SL heatmap exhibited nearly uniform SL shortening within and among the individual myocytes with some myocardia exhibiting nonuniform SLs. During diastole, the heart showed predominant SL elongation, which was also accompanied by patchy distributions of locally short-SL regions, reflecting inhomogeneous SLs. This SL inhomogeneity was attenuated by pharmacological relaxation by 2,3-butanedione monoxime. The heatmap of the rapidly-frozen heart during ventricular fibrillation also revealed inhomogeneous SLs within and among individual myocytes. Overall, cardiac phase-targeting cryofixation unveiled in-depth behaviors on SL in the heart. Our cryofixation strategy will open a new horizon to clarify precise spatiotemporal changes in sarcomere structures and understand cardiac functions.", "classifications": [ { "id": "JPMJCR1925", "label": "JPMJCR1925", "researcher": "Katsumasa Fujita", "type": "grant" }, { "id": "Fujita", "label": "Group Fujita", "parent": "Fujita", "type": "group" }, { "id": "Tanaka", "label": "Group Tanaka", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Shoko", "last_name": "Tamura", "name": null }, { "creator_type": "author", "first_name": "Kentaro", "last_name": "Mochizuki", "name": null }, { "creator_type": "author", "first_name": "Yasuaki", "last_name": "Kumamoto", "name": null }, { "creator_type": "author", "first_name": "Yuma", "last_name": "Morishita", "name": null }, { "creator_type": "author", "first_name": "Masahito", "last_name": "Yamanaka", "name": null }, { "creator_type": "author", "first_name": "Wen-Jin", "last_name": "Ho", "name": null }, { "creator_type": "author", "first_name": "Yoshinori", "last_name": "Harada", "name": null }, { "creator_type": "author", "first_name": "Katsumasa", "last_name": "Fujita", "name": null }, { "creator_type": "author", "first_name": "Hideo", "last_name": "Tanaka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41598-026-41756-0" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "41764337" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cryopreservation", "descriptor_ui": "D015925", "major_topic": true }, { "descriptor": "Diacetyl", "descriptor_ui": "D003931", "major_topic": false }, { "descriptor": "Diastole", "descriptor_ui": "D003971", "major_topic": false }, { "descriptor": "Heart", "descriptor_ui": "D006321", "major_topic": true }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Myocardial Contraction", "descriptor_ui": "D009200", "major_topic": true }, { "descriptor": "Myocardium", "descriptor_ui": "D009206", "major_topic": false }, { "descriptor": "Myocytes, Cardiac", "descriptor_ui": "D032383", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Sarcomeres", "descriptor_ui": "D012518", "major_topic": true }, { "descriptor": "Systole", "descriptor_ui": "D013599", "major_topic": false } ], "publication": { "conference_name": null, "date": "2026 Feb 28", "date_precision": "day", "issue": "", "normalized_date": "2026-02-28", "pages": "", "proceedings_title": null, "publisher": "", "title": "Scientific reports", "volume": "", "year": 2026 }, "ssbd": { "database": [], "repository": [ "ssbd-repos-000488" ] }, "title": "Phase-targeting rapid cryofixation of the beating heart and histological analysis unveil contractile state-dependent sarcomere dynamics.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Macrocyclic peptides have garnered increasing attention due to their therapeutic potential. However, the low cell membrane permeability of macrocyclic peptides limits their access to intracellular targets. This study aimed to apply live-cell Raman imaging to detect intracellular macrocyclic peptides as a potential therapeutic modality. Alkyne-tags with specific Raman bands were attached to several types of macrocyclic peptides originally designed as HIV protease inhibitors. Membrane permeability was measured by using the traditional penetration test. Variations in permeability were observed among the compounds, with the alkyne group showing a minimal effect on the results. Macrocyclic peptides with an alkyne-tag, which exhibited no permeability in the penetration test, were added to the live cells and evaluated using Raman imaging. Two-dimensional (2D) and three-dimensional (3D) Raman imaging detected the macrocyclic peptides in the intracellular region. However, the alkyne signal was not observed in cells treated with the macrocyclic peptides, showing cell penetration in the penetration test. These results are consistent with the observed pharmacological activities and suggest that the traditional penetration test may be insufficient for effective drug design of macrocyclic peptides. We conclude that combining emerging techniques, such as Raman imaging, with traditional methods can provide a more detailed evaluation of the permeability of macrocyclic peptides.", "classifications": [ { "id": "Fujita", "label": "Group Fujita", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yasunori", "last_name": "Nawa", "name": null }, { "creator_type": "author", "first_name": "Tetsuya", "last_name": "Miyano", "name": null }, { "creator_type": "author", "first_name": "Kazuki", "last_name": "Bando", "name": null }, { "creator_type": "author", "first_name": "Shungo", "last_name": "Mitsuki", "name": null }, { "creator_type": "author", "first_name": "Kyohei", "last_name": "Hayashi", "name": null }, { "creator_type": "author", "first_name": "Yoshikazu", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Ueda", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Fujita", "name": null }, { "creator_type": "author", "first_name": "Katsumasa", "last_name": "Fujita", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/cbmi.5c00052" }, "pmcid": { "normalized": "PMC12933483" }, "pmid": { "normalized": "41756774" } }, "mesh": [], "publication": { "conference_name": null, "date": "2026 Feb 23", "date_precision": "day", "issue": "2", "normalized_date": "2026-02-23", "pages": "167-177", "proceedings_title": null, "publisher": "", "title": "Chemical & biomedical imaging", "volume": "4", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "Live-Cell Raman Imaging Elucidates Intracellular Distribution of Macrocyclic Peptides Designed as HIV Protease Inhibitors.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Reactive Oxygen Species (ROS), which play a critical role in cellular signaling pathways, are one of the chemical products caused by ultrasound irradiation. In general, ROS generation has been ignored in terms of high-frequency ultrasound (>5 MHz) due to the limitation of cavitation induction. However, does high-frequency ultrasound not affect the production of ROS in cells? Here, we propose comparing ROS in solution and intracellular ROS generation by ultrasound at high frequency (6.5 MHz) and at a common frequency (1 MHz) in medical ultrasound applications, thereby elucidating the capabilities of high-frequency ultrasound on cells by ROS production. We discovered that 6.5 MHz ultrasound, as irradiated by a lithium niobate transducer, generates intracellular ROS more than conventional 1.0 MHz ultrasound. The phenomenon of ROS production by high-frequency ultrasound having high spatial resolution demonstrated the possibility that ultrasound is capable of effectively generating intracellular ROS at the cellular level.", "classifications": [ { "id": "Kuchimaru", "label": "Group Kuchimaru", "parent": "Shintaku", "type": "group" }, { "id": "Shintaku", "label": "Team Shintaku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Kotaro", "last_name": "Fujishiro", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Okada", "name": null }, { "creator_type": "author", "first_name": "Filippo", "last_name": "Rossi", "name": null }, { "creator_type": "author", "first_name": "Takahiro", "last_name": "Kuchimaru", "name": null }, { "creator_type": "author", "first_name": "Yuta", "last_name": "Kurashina", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/advs.202519582" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "41722057" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Niobium", "descriptor_ui": "D009556", "major_topic": false }, { "descriptor": "Oxides", "descriptor_ui": "D010087", "major_topic": false }, { "descriptor": "Reactive Oxygen Species", "descriptor_ui": "D017382", "major_topic": true }, { "descriptor": "Ultrasonic Waves", "descriptor_ui": "D000069453", "major_topic": true }, { "descriptor": "Vibration", "descriptor_ui": "D014732", "major_topic": true } ], "publication": { "conference_name": null, "date": "2026 Feb 21", "date_precision": "day", "issue": "", "normalized_date": "2026-02-21", "pages": "e19582", "proceedings_title": null, "publisher": "", "title": "Advanced science (Weinheim, Baden-Wurttemberg, Germany)", "volume": "", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "Intracellular Reactive Oxygen Species Generation Induced by High-Frequency Ultrasound in Thickness Vibration Mode.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The orbitofrontal cortex (OFC) is central to cognitive and social functions, yet its presynaptic partners remain incompletely defined. In female mice, the OFC modulates infant-directed caregiving behaviors in an experience-dependent manner. Here, we identify the submedius thalamus (SMT) as a major presynaptic partner of the OFC. Trans-synaptic tracing revealed intensive inputs from both the SMT and mediodorsal thalamus (MD) to OFC layer 5 excitatory neurons. We generated a Tnnt1-Cre mouse line that enables selective targeting of these higher-order thalamic nuclei. Axonal tracing demonstrated complementary projection patterns of the SMT and MD across prefrontal regions. Microendoscopic Ca(2+) imaging demonstrated pup retrieval-related activity in both SMT and MD, with SMT exhibiting learning-related plasticity. Projection-specific chemogenetic silencing demonstrated that SMT modulates OFC activity during pup retrieval, although its behavioral relevance appeared limited. Collectively, our study provides a presynaptic map of OFC layer 5 neurons and a proof of concept for selective manipulation of the SMT as a previously understudied thalamic input to the OFC.", "classifications": [ { "id": "Miyamichi", "label": "Group Miyamichi", "parent": "Enomoto", "type": "group" }, { "id": "Enomoto", "label": "Team Enomoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Gen-Ichi", "last_name": "Tasaka", "name": null }, { "creator_type": "author", "first_name": "Mitsue", "last_name": "Hagihara", "name": null }, { "creator_type": "author", "first_name": "Haruna", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Miho", "last_name": "Kihara", "name": null }, { "creator_type": "author", "first_name": "Takaya", "last_name": "Abe", "name": null }, { "creator_type": "author", "first_name": "Kazunari", "last_name": "Miyamichi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.isci.2026.114828" }, "pmcid": { "normalized": "PMC12914318" }, "pmid": { "normalized": "41716988" } }, "mesh": [], "publication": { "conference_name": null, "date": "2026 Feb 20", "date_precision": "day", "issue": "2", "normalized_date": "2026-02-20", "pages": "114828", "proceedings_title": null, "publisher": "", "title": "iScience", "volume": "29", "year": 2026 }, "ssbd": { "database": [ "ssbd-database-000487" ], "repository": [ "ssbd-repos-000487" ] }, "title": "Submedius thalamic inputs shape the presynaptic architecture of layer 5 orbitofrontal cortex in mice.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUNDS: The cellular slime mold Dictyostelium discoideum is a widely used model system for studying basic processes in cell and developmental biology. While genetic tools, such as targeted gene disruption by homologous recombination and genome editing using CRISPR/Cas9, are well-established in D. discoideum, efficient methods for conditional loss-of-function studies are limited. Here, we developed a nanobody-based degron system for D. discoideum based on ALFA-tagged protein recruitment to the Skp1-Cullin-F-box (SCF) complex. RESULTS: ALFA-tagged Histone H1 was efficiently degraded by expressing anti-ALFA nanobody (NbALFA) fused to the D. discoideum FbxD F-box domain ('dictyGrad-ALFA'). Cell type-specific targeting was achieved by expressing dictyGrad-ALFA under prestalk- and prespore-specific gene promoters. Furthermore, targeting of adenylyl cyclase A (ACA) resulted in the expected aggregation-deficient phenotype, validating the efficacy of dictyGrad-ALFA-mediated protein depletion. Cell type-specific ACA degradation delayed development but eventually resulted in normal fruiting bodies. Our ALFA-tag approach was further used for conditional knockdown in combination with the auxin-inducible degron 2 (AID2) system, which relies on indole-3-acetic acid (IAA)-dependent binding between NbALFA-mAID and a OsTIR-F-box-Skp1A fusion protein. We obtained efficient IAA-induced degradation in prestalk cells; however, efficiency was low in other cell types. CONCLUSIONS: Together, these systems pave the way for conditional and cell type-specific protein degradation in D. discoideum, enabling functional analyses of genes essential for growth and development.", "classifications": [ { "id": "JPMJCR1923", "label": "JPMJCR1923", "researcher": "Satoshi Sawai", "type": "grant" }, { "id": "Sawai", "label": "Group Sawai", "parent": "Sawai", "type": "group" }, { "id": "Sawai", "label": "Team Sawai", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Hidenori", "last_name": "Hashimura", "name": null }, { "creator_type": "author", "first_name": "Shoko", "last_name": "Fujishiro", "name": null }, { "creator_type": "author", "first_name": "Nao", "last_name": "Shimada", "name": null }, { "creator_type": "author", "first_name": "Tomoko", "last_name": "Adachi", "name": null }, { "creator_type": "author", "first_name": "Toyoko", "last_name": "Sugita", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Kuwana", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Sawai", "name": null } ], "identifiers": { "doi": { "normalized": "10.1186/s12860-026-00572-0" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "41714934" } }, "mesh": [ { "descriptor": "Degrons", "descriptor_ui": "D000097791", "major_topic": false }, { "descriptor": "Dictyostelium", "descriptor_ui": "D004023", "major_topic": true }, { "descriptor": "Gene Knockdown Techniques", "descriptor_ui": "D055785", "major_topic": true }, { "descriptor": "Histones", "descriptor_ui": "D006657", "major_topic": false }, { "descriptor": "Proteolysis", "descriptor_ui": "D059748", "major_topic": false }, { "descriptor": "Protozoan Proteins", "descriptor_ui": "D015800", "major_topic": true }, { "descriptor": "Single-Domain Antibodies", "descriptor_ui": "D061905", "major_topic": true } ], "publication": { "conference_name": null, "date": "2026 Feb 19", "date_precision": "day", "issue": "", "normalized_date": "2026-02-19", "pages": "", "proceedings_title": null, "publisher": "", "title": "BMC molecular and cell biology", "volume": "", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "A nanobody-based degron system for targeted protein knockdown in Dictyostelium discoideum.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Basement membranes (BMs) are specialized extracellular matrices (ECMs) essential for tissue structure and function. In non-vertebrates, ECM components can be produced both locally and by distant tissues. In contrast, mammalian ECM has traditionally been considered to originate predominantly from adjacent or tissue-resident cells. The kidney glomerular basement membrane (GBM), composed of laminin-alpha5beta2gamma1 and collagen-alpha3alpha4alpha5(IV), is produced by neighboring cells and functions as a filtration barrier. Alport syndrome, a genetic kidney disease, is characterized by GBM structural defects and ectopic laminin-alpha2 deposition, but the source of this laminin remains unknown. Here, using CRISPR-Cas9 transgenic models, we demonstrated that ectopic laminin-alpha2 in GBM originates not from local kidney cells but from the circulation. Furthermore, laminin-alpha2 in the mesangium partially derives from circulating sources even under healthy conditions. Our findings uncover a non-cell-autonomous mechanism whereby GBM integrity regulates circulating protein incorporation, revealing a trans-tissue regulation of BM composition in mammals.", "classifications": [ { "id": "Fujiwara", "label": "Group Fujiwara", "parent": "Fujiwara", "type": "group" }, { "id": "Fujiwara", "label": "Team Fujiwara", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Kohei", "last_name": "Omachi", "name": null }, { "creator_type": "author", "first_name": "Meei-Hua", "last_name": "Lin", "name": null }, { "creator_type": "author", "first_name": "Pongpratch", "last_name": "Puapatanakul", "name": null }, { "creator_type": "author", "first_name": "Joshua F.", "last_name": "Begin", "name": null }, { "creator_type": "author", "first_name": "Karen K.", "last_name": "McKee", "name": null }, { "creator_type": "author", "first_name": "Hironobu", "last_name": "Fujiwara", "name": null }, { "creator_type": "author", "first_name": "Peter D.", "last_name": "Yurchenco", "name": null }, { "creator_type": "author", "first_name": "Jeffrey H.", "last_name": "Miner", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.celrep.2026.117006" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "41712384" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Extracellular Matrix", "descriptor_ui": "D005109", "major_topic": false }, { "descriptor": "Glomerular Basement Membrane", "descriptor_ui": "D050533", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Kidney", "descriptor_ui": "D007668", "major_topic": true }, { "descriptor": "Laminin", "descriptor_ui": "D007797", "major_topic": true }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Transgenic", "descriptor_ui": "D008822", "major_topic": false }, { "descriptor": "Nephritis, Hereditary", "descriptor_ui": "D009394", "major_topic": false } ], "publication": { "conference_name": null, "date": "2026 Feb 18", "date_precision": "day", "issue": "3", "normalized_date": "2026-02-18", "pages": "117006", "proceedings_title": null, "publisher": "", "title": "Cell reports", "volume": "45", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "Glomerular basement membrane structural integrity dictates trans-tissue deposition of laminin in the kidney.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Self-DNA triggers cGAS-STING-mediated type I interferon (IFN-I) to induce both protective and pathogenic immune responses; however, how self-DNA activates the cytosolic cGAS-STING pathway remains unclear. Here we show that the cGAS/STING/IFN-I axis is activated by self-DNA via a process termed 'nucleocytosis', in which nuclear DNA is extracted from dying cells by macrophages. Mechanistically, lysosomal malfunction, via both proton loss and palmitoyl-protein thioesterase 1 (PPT1) inhibition, triggers cell death and calreticulin accumulation in the nuclei. Live-cell imaging of secretion activity reveals that macrophages access the calreticulin-enriched nuclei of dying cells and extract DNA for cGAS-STING activation. Consistent with these findings, PPT1-targeting cationic amphiphilic drugs induce a cGAS-STING-dependent IFN-I response in vitro and in vivo. Our findings thus identify nucleocytosis as a macrophage function for nuclear DNA extraction and induction of the cGAS/IFN-I axis, and suggest that nucleocytosis-inducing cell death could be a druggable target for treating self-DNA-related inflammatory diseases.", "classifications": [ { "id": "Takekawa", "label": "Group Takekawa", "parent": "Takekawa", "type": "group" }, { "id": "Takekawa", "label": "Team Takekawa", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Hideo", "last_name": "Negishi", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Wada", "name": null }, { "creator_type": "author", "first_name": "Yoshitaka", "last_name": "Shirasaki", "name": null }, { "creator_type": "author", "first_name": "Tomoya", "last_name": "Hayashi", "name": null }, { "creator_type": "author", "first_name": "Yuji", "last_name": "Kubota", "name": null }, { "creator_type": "author", "first_name": "Tomio", "last_name": "Iwasaki", "name": null }, { "creator_type": "author", "first_name": "Mina", "last_name": "Kurosawa", "name": null }, { "creator_type": "author", "first_name": "Tatsuma", "last_name": "Ban", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Muto", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Suenaga", "name": null }, { "creator_type": "author", "first_name": "Taichi", "last_name": "Kojima", "name": null }, { "creator_type": "author", "first_name": "Yuzuki", "last_name": "Matsuda", "name": null }, { "creator_type": "author", "first_name": "Sean Lord", "last_name": "Irish", "name": null }, { "creator_type": "author", "first_name": "Kosuke", "last_name": "Dodo", "name": null }, { "creator_type": "author", "first_name": "Toru", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Mai", "last_name": "Yamagishi", "name": null }, { "creator_type": "author", "first_name": "Burcu", "last_name": "Temizoz", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Yoshimori", "name": null }, { "creator_type": "author", "first_name": "Chisato", "last_name": "Kanai", "name": null }, { "creator_type": "author", "first_name": "Yoji", "last_name": "Nagasaki", "name": null }, { "creator_type": "author", "first_name": "Masaki", "last_name": "Ohmuraya", "name": null }, { "creator_type": "author", "first_name": "Tomohiko", "last_name": "Tamura", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Iwama", "name": null }, { "creator_type": "author", "first_name": "Toshifumi", "last_name": "Inada", "name": null }, { "creator_type": "author", "first_name": "Etsushi", "last_name": "Kuroda", "name": null }, { "creator_type": "author", "first_name": "Kouji", "last_name": "Kobiyama", "name": null }, { "creator_type": "author", "first_name": "Noriko", "last_name": "Toyama-Sorimachi", "name": null }, { "creator_type": "author", "first_name": "Mutsuhiro", "last_name": "Takekawa", "name": null }, { "creator_type": "author", "first_name": "Cevayir", "last_name": "Coban", "name": null }, { "creator_type": "author", "first_name": "Ken J.", "last_name": "Ishii", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41467-026-68839-w" }, "pmcid": { "normalized": "PMC12917151" }, "pmid": { "normalized": "41708603" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Calreticulin", "descriptor_ui": "D037282", "major_topic": false }, { "descriptor": "Cell Death", "descriptor_ui": "D016923", "major_topic": false }, { "descriptor": "Cell Nucleus", "descriptor_ui": "D002467", "major_topic": true }, { "descriptor": "cGAS-STING Signaling Pathway", "descriptor_ui": "D000099196", "major_topic": false }, { "descriptor": "Cyclic Guanosine Monophosphate-Adenosine Monophosphate Synthase", "descriptor_ui": "D000099235", "major_topic": false }, { "descriptor": "DNA", "descriptor_ui": "D004247", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Interferon Type I", "descriptor_ui": "D007370", "major_topic": true }, { "descriptor": "Macrophages", "descriptor_ui": "D008264", "major_topic": false }, { "descriptor": "Membrane Proteins", "descriptor_ui": "D008565", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Nucleotidyltransferases", "descriptor_ui": "D009713", "major_topic": true }, { "descriptor": "STING Protein", "descriptor_ui": "D000099197", "major_topic": false } ], "publication": { "conference_name": null, "date": "2026 Feb 18", "date_precision": "day", "issue": "1", "normalized_date": "2026-02-18", "pages": "1658", "proceedings_title": null, "publisher": "", "title": "Nature communications", "volume": "17", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "cGAS-IFN-I responses by extracting nuclear DNA from dying cells via nucleocytosis.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Idiopathic pulmonary fibrosis (IPF) is characterized by progressive scarring of lung tissue with an urgent need for effective treatments. Studies have shown that the alveolar transitional cell state (ATCS) emerges in fibrotic regions of the IPF lung. However, whether ATCS is the cause or consequence of fibrosis is controversial, and no therapeutic agents targeting the alveolar epithelial differentiation are used to treat IPF. In this study, we performed a drug screening with an in vitro pulmonary fibrosis model using fibroblast-dependent alveolar organoids derived from human induced pluripotent stem cells (iPSCs) and identified p300/CBP inhibitors as candidate therapeutic agents. Multi-omics technology revealed that ATCS induced from human iPSCs-derived alveolar organoids had a compatible profile with that reported in IPF and p300/CBP inhibitors suppressed the emergence of ATCS. Overall, these results elucidate the biological mechanisms of pulmonary fibrosis and provide a potential therapeutic target.", "classifications": [ { "id": "Yamamoto", "label": "Group Yamamoto", "parent": "Toyoshima", "type": "group" }, { "id": "Toyoshima", "label": "Team Toyoshima", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yusuke", "last_name": "Tsutsui", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Masui", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Konishi", "name": null }, { "creator_type": "author", "first_name": "Taro", "last_name": "Tsujimura", "name": null }, { "creator_type": "author", "first_name": "Mio", "last_name": "Iwasaki", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Shimpei", "last_name": "Gotoh", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41467-026-68909-z" }, "pmcid": { "normalized": "PMC12901050" }, "pmid": { "normalized": "41680175" } }, "mesh": [ { "descriptor": "Alveolar Epithelial Cells", "descriptor_ui": "D056809", "major_topic": true }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "E1A-Associated p300 Protein", "descriptor_ui": "D050881", "major_topic": true }, { "descriptor": "Fibroblasts", "descriptor_ui": "D005347", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Idiopathic Pulmonary Fibrosis", "descriptor_ui": "D054990", "major_topic": true }, { "descriptor": "Induced Pluripotent Stem Cells", "descriptor_ui": "D057026", "major_topic": true }, { "descriptor": "Organoids", "descriptor_ui": "D009940", "major_topic": false }, { "descriptor": "p300-CBP Transcription Factors", "descriptor_ui": "D050880", "major_topic": true }, { "descriptor": "Pulmonary Alveoli", "descriptor_ui": "D011650", "major_topic": true }, { "descriptor": "Pulmonary Fibrosis", "descriptor_ui": "D011658", "major_topic": false } ], "publication": { "conference_name": null, "date": "2026 Feb 12", "date_precision": "day", "issue": "1", "normalized_date": "2026-02-12", "pages": "1214", "proceedings_title": null, "publisher": "", "title": "Nature communications", "volume": "17", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "Human iPSC-based Modeling of Pulmonary Fibrosis Reveals p300/CBP Inhibition Suppresses Alveolar Transitional Cell State.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Nuclear protein in testis (NUT) carcinoma is an extremely rare and aggressive malignancy characterized by NUTM1 gene rearrangement. It frequently develops in the lungs or the head and neck region as a poorly differentiated squamous cell carcinoma. The prognosis is generally poor and particularly dismal in cases with a pulmonary origin. Given the lack of an established standard treatment and the rapid disease progression, recently, immune checkpoint inhibitors (ICIs) have attracted attention, particularly in combination with platinum-based chemotherapy. We report a case series of four patients with pulmonary NUT carcinoma who received ICI-containing regimens as first-line therapy. Three patients received ICIs in combination with platinum-based chemotherapy and showed transient tumor shrinkage, although all ultimately experienced disease progression and died. One patient received ICI monotherapy owing to poor performance status and showed no clinical response. The median progression-free and overall survival were 53 and 108 days, respectively. Given the limited treatment options for NUT carcinoma, a combination of ICIs with platinum-based chemotherapy may represent a potential first-line treatment option. However, their efficacy remains limited.", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Tomoaki", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Akihiko", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Akiko", "last_name": "Tateishi", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Shinno", "name": null }, { "creator_type": "author", "first_name": "Yuji", "last_name": "Matsumoto", "name": null }, { "creator_type": "author", "first_name": "Tomonori", "last_name": "Mizutani", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Okuma", "name": null }, { "creator_type": "author", "first_name": "Hidehito", "last_name": "Horinouchi", "name": null }, { "creator_type": "author", "first_name": "Noboru", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Goto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1093/jjco/hyag025" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "41671149" } }, "mesh": [ { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Antineoplastic Combined Chemotherapy Protocols", "descriptor_ui": "D000971", "major_topic": true }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Immune Checkpoint Inhibitors", "descriptor_ui": "D000082082", "major_topic": true }, { "descriptor": "Lung Neoplasms", "descriptor_ui": "D008175", "major_topic": true }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Neoplasm Proteins", "descriptor_ui": "D009363", "major_topic": false }, { "descriptor": "Nuclear Proteins", "descriptor_ui": "D009687", "major_topic": true }, { "descriptor": "Oncogene Proteins", "descriptor_ui": "D015513", "major_topic": false }, { "descriptor": "Young Adult", "descriptor_ui": "D055815", "major_topic": false } ], "publication": { "conference_name": null, "date": "2026 Feb 11", "date_precision": "day", "issue": "", "normalized_date": "2026-02-11", "pages": "hyag025", "proceedings_title": null, "publisher": "", "title": "Japanese journal of clinical oncology", "volume": "", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "Immune checkpoint inhibitors in nuclear protein in testis carcinoma treatment: evidence of limited clinical benefits from a case series.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Microtubules are cytoskeletal filaments that self-assemble from the protein tubulin, a heterodimer of alpha-tubulin and beta-tubulin, and are important for cell mechanics, migration, and division. Much work has focused on how the nucleotide state of beta-tubulin regulates the structure and dynamics of microtubules. In contrast, less is known about the structure and function of the C-terminal tails (CTTs) of alpha- and beta-tubulin which are thought to freely protrude from the surface of the microtubule. To study the CTT of alpha-tubulin, we developed three different biosensors that bind the tyrosinated alpha-tubulin CTT (Y-alphaCTT). Surprisingly, live imaging of the probes indicates that the Y-alphaCTT is minimally accessible along the microtubule lattice under normal cellular conditions. Lattice binding of the Y-alphaCTT probes can be increased by three different ways of changing the tubulin conformational state: the drug Taxol, expression of microtubule-associated proteins (MAPs) that recognize or promote an expanded tubulin conformation, or expression of tubulin that cannot hydrolyze GTP. Molecular dynamics simulations indicate that the Y-alphaCTT undergoes numerous transient interactions with the bodies of alpha-tubulin and beta-tubulin in the lattice, and that the frequency of these interactions is regulated by the tubulin nucleotide state. These findings suggest that accessibility of the Y-alphaCTT is locally governed by nucleotide- and MAP-dependent conformational changes to tubulin subunits within the microtubule lattice.", "classifications": [ { "id": "Higaki", "label": "Group Higaki", "parent": "Ueda", "type": "group" }, { "id": "Ueda", "label": "Team Ueda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Takashi", "last_name": "Hotta", "name": null }, { "creator_type": "author", "first_name": "Morgan L.", "last_name": "Pimm", "name": null }, { "creator_type": "author", "first_name": "Ezekiel C.", "last_name": "Thomas", "name": null }, { "creator_type": "author", "first_name": "Yang", "last_name": "Yue", "name": null }, { "creator_type": "author", "first_name": "Patrick", "last_name": "DeLear", "name": null }, { "creator_type": "author", "first_name": "Lynne", "last_name": "Blasius", "name": null }, { "creator_type": "author", "first_name": "Michael A.", "last_name": "Cianfrocco", "name": null }, { "creator_type": "author", "first_name": "Morgan E.", "last_name": "DeSantis", "name": null }, { "creator_type": "author", "first_name": "Ryota", "last_name": "Horiuchi", "name": null }, { "creator_type": "author", "first_name": "Takumi", "last_name": "Higaki", "name": null }, { "creator_type": "author", "first_name": "David", "last_name": "Sept", "name": null }, { "creator_type": "author", "first_name": "Ryoma", "last_name": "Ohi", "name": null }, { "creator_type": "author", "first_name": "Kristen J.", "last_name": "Verhey", "name": null } ], "identifiers": { "doi": { "normalized": "10.7554/elife.109308" }, "pmcid": { "normalized": "PMC12885479" }, "pmid": { "normalized": "41662400" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Guanosine Triphosphate", "descriptor_ui": "D006160", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Microtubule-Associated Proteins", "descriptor_ui": "D008869", "major_topic": false }, { "descriptor": "Microtubules", "descriptor_ui": "D008870", "major_topic": true }, { "descriptor": "Molecular Dynamics Simulation", "descriptor_ui": "D056004", "major_topic": false }, { "descriptor": "Paclitaxel", "descriptor_ui": "D017239", "major_topic": false }, { "descriptor": "Protein Binding", "descriptor_ui": "D011485", "major_topic": false }, { "descriptor": "Protein Conformation", "descriptor_ui": "D011487", "major_topic": false }, { "descriptor": "Tubulin", "descriptor_ui": "D014404", "major_topic": true } ], "publication": { "conference_name": null, "date": "2026 Feb 9", "date_precision": "day", "issue": "", "normalized_date": "2026-02-09", "pages": "", "proceedings_title": null, "publisher": "", "title": "eLife", "volume": "14", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "Accessibility of the unstructured alpha-tubulin C-terminal tail is controlled by microtubule lattice conformation.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The paramount challenge in precision oncology lies in further improving quality of life and response rates for individual patients. Efforts toward these goals are steadily expanding the scope of clinical implementation, despite ongoing challenges such as standardization, cost-effectiveness, and data harmonization. Building upon this maturing foundation, generative AI-which has evolved dramatically in recent years-is particularly valuable at this stage of advancing efficiency and adoption as an auxiliary technology linking literature, guidelines, trial protocols, and patient data. Specifically, through mutation interpretation, trial eligibility matching, and tumor board support, it is expected to contribute to advancing standardization, improving cost-effectiveness, accelerating data harmonization, and further accelerating human-centered decision-making. Accordingly, this review surveys the development history of generative AI and its current healthcare applications, organizing its implementation potential for precision oncology along three axes: (1) generative AI-based interpretation of genetic mutations and estimation of their pathological significance; (2) generative AI-driven verification of clinical trial eligibility; and (3) multimodal foundation models for imaging and pathology that compute \"tumor phenotypes\" using real-world data, contributing to report drafting and molecular surrogate estimation. In response, we propose a strategy centered on retrieval-augmented generation (RAG) and human-in-the-loop (HITL) workflows, encompassing data preparation based on OMOP, mCODE, and FHIR; multicenter prospective evaluation; auditable logs and governance aligned with Good Manufacturing Practice (GMP) and the EU AI Act; and a synthetic data strategy including differential privacy. Ultimately, this approach validates value through real-world outcomes and charts a path toward \"learning oncology,\" accelerating patient-centered decision-making and clinical trial development.", "classifications": [ { "id": "Hamamoto", "label": "Group Hamamoto", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Ryuji", "last_name": "Hamamoto", "name": null }, { "creator_type": "author", "first_name": "Takafumi", "last_name": "Koyama", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Tomohiro", "last_name": "Yasuda", "name": null }, { "creator_type": "author", "first_name": "Kazuma", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Yu", "last_name": "Akagi", "name": null }, { "creator_type": "author", "first_name": "Nobuji", "last_name": "Kouno", "name": null }, { "creator_type": "author", "first_name": "Kazuki", "last_name": "Sudo", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Hirata", "name": null }, { "creator_type": "author", "first_name": "Kuniko", "last_name": "Sunami", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Kubo", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Katayama", "name": null }, { "creator_type": "author", "first_name": "Atsuo", "last_name": "Takashima", "name": null }, { "creator_type": "author", "first_name": "Tomonori", "last_name": "Taniguchi", "name": null }, { "creator_type": "author", "first_name": "Hiromi", "last_name": "Matsumoto", "name": null }, { "creator_type": "author", "first_name": "Ryota", "last_name": "Shibaki", "name": null }, { "creator_type": "author", "first_name": "Ken", "last_name": "Asada", "name": null }, { "creator_type": "author", "first_name": "Masaaki", "last_name": "Komatsu", "name": null }, { "creator_type": "author", "first_name": "Syuzo", "last_name": "Kaneko", "name": null }, { "creator_type": "author", "first_name": "Masayoshi", "last_name": "Yamada", "name": null }, { "creator_type": "author", "first_name": "Hidehito", "last_name": "Horinouchi", "name": null }, { "creator_type": "author", "first_name": "Katsuya", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Goto", "name": null }, { "creator_type": "author", "first_name": "Ken", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Yutaka", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Kenichi", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Noboru", "last_name": "Yamamoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1186/s13045-026-01781-y" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "41664164" } }, "mesh": [ { "descriptor": "Artificial Intelligence", "descriptor_ui": "D001185", "major_topic": true }, { "descriptor": "Generative Artificial Intelligence", "descriptor_ui": "D000098842", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Medical Oncology", "descriptor_ui": "D008495", "major_topic": true }, { "descriptor": "Neoplasms", "descriptor_ui": "D009369", "major_topic": true }, { "descriptor": "Precision Medicine", "descriptor_ui": "D057285", "major_topic": true } ], "publication": { "conference_name": null, "date": "2026 Feb 9", "date_precision": "day", "issue": "", "normalized_date": "2026-02-09", "pages": "", "proceedings_title": null, "publisher": "", "title": "Journal of hematology & oncology", "volume": "", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "Implementing generative artificial intelligence in precision oncology: safety, governance, and significance.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Reprogramming of cellular metabolism is a hallmark of cancer, particularly ovarian cancer (OC), that contributes to rapid cancer growth and survival. However, studies using clinical specimens are limited. To identify metabolic alterations specific to OC, we performed metabolomic analysis of OC and benign ovarian tumors. The relationship between metabolomics and transcriptomics was investigated by transcriptome analysis. Fifty-one patients with OC and three with benign ovarian tumors, diagnosed between 2011 and 2014 using available frozen tissue and plasma specimens, were enrolled at the National Cancer Center Hospital. To identify metabolic alterations, plasma samples from 51 patients with OC and three with benign tumors, along with both cancerous and non-cancerous tissue samples from 44 of the 51 patients with OC, were analyzed using gas chromatography-mass spectrometry. In addition, we performed transcriptomic analysis of cancerous tissues obtained from 39 of the 44 patients with OC. It was not possible to classify patients based on plasma metabolite levels; therefore, the 44 patients with OC were classified into two groups based on metabolite levels: high and low, based on tissue analysis. The group with high metabolite levels had more advanced-stage tumors (P = 0.02). Transcriptome pathway analysis revealed suppression of pathways related to natural killer (NK) cells and immune responses in the group with high metabolite levels. NK cell percentages were lower in the group with high metabolite levels than in the group with low metabolite levels (P = 0.04). Thus, the group with high metabolite levels was associated with advanced stages and a reduced fraction of NK cells, suggesting that high metabolite levels may play a direct or indirect role in immune activity or in the malignant progression of OC.", "classifications": [ { "id": "Hamamoto", "label": "Group Hamamoto", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Maiko", "last_name": "Yamaguchi", "name": null }, { "creator_type": "author", "first_name": "Daiki", "last_name": "Higuchi", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Erisa", "last_name": "Fujii", "name": null }, { "creator_type": "author", "first_name": "Mayumi Kobayashi", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Kengo", "last_name": "Hiranuma", "name": null }, { "creator_type": "author", "first_name": "Yuka", "last_name": "Asami", "name": null }, { "creator_type": "author", "first_name": "Hanako", "last_name": "Ono", "name": null }, { "creator_type": "author", "first_name": "Takafumi", "last_name": "Koyama", "name": null }, { "creator_type": "author", "first_name": "Masaaki", "last_name": "Komatsu", "name": null }, { "creator_type": "author", "first_name": "Ryuji", "last_name": "Hamamoto", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Matsumoto", "name": null }, { "creator_type": "author", "first_name": "Akihiko", "last_name": "Sekizawa", "name": null }, { "creator_type": "author", "first_name": "Yasuhisa", "last_name": "Terao", "name": null }, { "creator_type": "author", "first_name": "Atsuo", "last_name": "Itakura", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Kohno", "name": null }, { "creator_type": "author", "first_name": "Tomoyasu", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Hideki", "last_name": "Makinoshima", "name": null }, { "creator_type": "author", "first_name": "Mitsuya", "last_name": "Ishikawa", "name": null }, { "creator_type": "author", "first_name": "Kouya", "last_name": "Shiraishi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41598-026-38014-8" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "41644592" } }, "mesh": [ { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Gene Expression Profiling", "descriptor_ui": "D020869", "major_topic": true }, { "descriptor": "Gene Expression Regulation, Neoplastic", "descriptor_ui": "D015972", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Killer Cells, Natural", "descriptor_ui": "D007694", "major_topic": false }, { "descriptor": "Metabolome", "descriptor_ui": "D055442", "major_topic": true }, { "descriptor": "Metabolomics", "descriptor_ui": "D055432", "major_topic": true }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Ovarian Neoplasms", "descriptor_ui": "D010051", "major_topic": true }, { "descriptor": "Transcriptome", "descriptor_ui": "D059467", "major_topic": true } ], "publication": { "conference_name": null, "date": "2026 Feb 5", "date_precision": "day", "issue": "", "normalized_date": "2026-02-05", "pages": "", "proceedings_title": null, "publisher": "", "title": "Scientific reports", "volume": "", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "Metabolomic and transcriptomic analyses identify metabolic alterations and immune suppression in ovarian cancer.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "High-throughput, label-free monitoring of cellular differentiation remains a major challenge in stem cell biology and regenerative medicine. Raman spectroscopy offers rich molecular specificity without perturbing the cell state, but the analytical complexity of large, unlabeled spectral data sets has limited its adoption. Here, we introduce a scalable computational framework that adapts algorithms from single-cell genomics for the analysis of line-illumination Raman spectroscopy data. Applying this approach, we track the stepwise differentiation of human induced pluripotent stem cells into hepatocyte-like cells at single-cell resolution across more than 1.8 million spectra. By integration of unsupervised clustering with supervised learning, our pipeline enables rapid analysis (<2 min per imaging field), monitoring key biochemical markers, such as cytochromes, glycogen, and lipids, and real-time discrimination of successful and aberrant differentiation without labeling. This work establishes a generalizable strategy for Raman-based cell state profiling and supports non-invasive, in-line monitoring in stem cell manufacturing pipelines.", "classifications": [ { "id": "Fujita", "label": "Group Fujita", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Piyush", "last_name": "Raj", "name": null }, { "creator_type": "author", "first_name": "Menglu", "last_name": "Li", "name": null }, { "creator_type": "author", "first_name": "Yukiko", "last_name": "Ueyama-Toba", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Mizuguchi", "name": null }, { "creator_type": "author", "first_name": "Katsumasa", "last_name": "Fujita", "name": null }, { "creator_type": "author", "first_name": "Ishan", "last_name": "Barman", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/acs.nanolett.5c05396" }, "pmcid": { "normalized": "PMC13040483" }, "pmid": { "normalized": "41571562" } }, "mesh": [ { "descriptor": "Algorithms", "descriptor_ui": "D000465", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": true }, { "descriptor": "Hepatocytes", "descriptor_ui": "D022781", "major_topic": true }, { "descriptor": "High-Throughput Screening Assays", "descriptor_ui": "D057166", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Induced Pluripotent Stem Cells", "descriptor_ui": "D057026", "major_topic": true }, { "descriptor": "Single-Cell Analysis", "descriptor_ui": "D059010", "major_topic": false }, { "descriptor": "Spectrum Analysis, Raman", "descriptor_ui": "D013059", "major_topic": true } ], "publication": { "conference_name": null, "date": "2026 Feb 4", "date_precision": "day", "issue": "4", "normalized_date": "2026-02-04", "pages": "1357-1365", "proceedings_title": null, "publisher": "", "title": "Nano letters", "volume": "26", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "Automated High-Throughput Raman Spectral Framework for Cellular Differentiation Monitoring.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Monoclonal antibodies (mAbs) are essential tools in life sciences and medicine because they provide high specificity and selective binding properties. However, their production is labor-intensive. Conventional hybridoma screening using the limiting dilution method requires repeated manual handling and long-term culture, which slows the isolation of target antibodies. To facilitate this process, we previously developed a membrane-type immunoglobulin-directed hybridoma screening (MIHS) method that directly detects interactions between membrane-bound B-cell receptors and fluorescently labeled antigens. However, the preparation of multiple soluble antigens remains a challenge. Hence, we designed a single recombinant antigen, X-His-BAP-MBP (X-HBM), in which the target antigen (X) was fused to a solubilization tag (MBP), biotinylation tag (BAP), and His-tag for purification. We established a dual-color MIHS system that integrates immunization, screening, and evaluation into a workflow. Dual-color fluorescence labeling enabled the discrimination and exclusion of hybridomas producing antibodies against MBP or tag sequences, allowing the precise isolation of hybridomas secreting antibodies specific to the target antigen. Using the mitochondrial enzyme CARS2 as a model antigen, the proportion of target-positive hybridomas increased approximately eightfold compared to that using the conventional method. Specific mAbs were successfully obtained using only a single soluble antigen preparation through the MIHS method. This method supports the efficient selection of antigen-specific hybridomas, even when solubilization tags are used, by achieving both antigen specificity and practical solubility.", "classifications": [ { "id": "Akaike", "label": "Group Akaike", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Mei", "last_name": "Kawamura", "name": null }, { "creator_type": "author", "first_name": "Fujino", "last_name": "Kuba", "name": null }, { "creator_type": "author", "first_name": "Atsumi", "last_name": "Sakaguchi", "name": null }, { "creator_type": "author", "first_name": "Kosei", "last_name": "Oishi", "name": null }, { "creator_type": "author", "first_name": "Tomoya", "last_name": "Sugiyama", "name": null }, { "creator_type": "author", "first_name": "Wakana", "last_name": "Ujiie", "name": null }, { "creator_type": "author", "first_name": "Soushi", "last_name": "Murayama", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Fujisawa", "name": null }, { "creator_type": "author", "first_name": "Sayaka", "last_name": "Kikuchi", "name": null }, { "creator_type": "author", "first_name": "Yoichiro", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Minkyung", "last_name": "Jung", "name": null }, { "creator_type": "author", "first_name": "Masanobu", "last_name": "Morita", "name": null }, { "creator_type": "author", "first_name": "Takaaki", "last_name": "Akaike", "name": null }, { "creator_type": "author", "first_name": "Yasuyuki", "last_name": "Kurihara", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.jbiosc.2026.01.004" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "41644376" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Antibodies, Monoclonal", "descriptor_ui": "D000911", "major_topic": true }, { "descriptor": "Antigens", "descriptor_ui": "D000941", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Hybridomas", "descriptor_ui": "D006825", "major_topic": true }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false } ], "publication": { "conference_name": null, "date": "2026 Feb 4", "date_precision": "day", "issue": "", "normalized_date": "2026-02-04", "pages": "S1389-1723(26)00029-0", "proceedings_title": null, "publisher": "", "title": "Journal of bioscience and bioengineering", "volume": "", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "Dual-color membrane-type immunoglobulin-directed hybridoma screening for selective and accelerated monoclonal antibody production.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Adults of Schistosoma mansoni reside in the mesenteric veins, where they are naturally exposed to high levels of hydrogen sulfide (H(2)S). S. mansoni and other intestinal parasites have adapted to this sulfide-rich environment, but the evolved mechanisms to metabolize sulfide remain unelucidated. Here we reveal that the putative sulfide:quinone oxidoreductase (SQOR) encoded by S. mansoni is indeed an SQOR, catalyzing the first step of sulfide metabolism. We demonstrated that S. mansoni SQOR (SmSQOR) is expressed in eggs, cercaria and adult stages and localized in the mitochondria. The reaction catalyzed by SmSQOR was investigated using sulfane sulfur probe 4 (SSP4) and shown to require the co-presence of sulfide, quinone, and a sulfur acceptor, indicating a quaternary complex-mediated mechanism. Unlike human and bacterial SQORs, purified SmSQOR could not reduce quinones in the presence of sulfide alone unless sulfite, cyanide, or L-cysteine (but not coenzyme A or glutathione) was provided as the sulfur acceptor. In the presence of these sulfur acceptors, SmSQOR formed a long-lived charge-transfer (CT) complex, a transient electronically coupled association between electron donor and acceptor, as indicated by a broad band around 637-755 nm in the spectrum, which was associated with a partial loss of enzyme activity. Moreover, residues critical for CT complex formation and SQOR catalysis were identified. Using SSP4, we also demonstrated that SQOR was active in S. mansoni adult, egg, and cercaria stages. Taken together, these features suggest that metabolism of sulfide proceeds differently in S. mansoni than in humans.", "classifications": [ { "id": "Akaike", "label": "Group Akaike", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Augustin Tshibaka", "last_name": "Kabongo", "name": null }, { "creator_type": "author", "first_name": "Talaam Keith", "last_name": "Kiplangat", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Tayama", "name": null }, { "creator_type": "author", "first_name": "Acharjee", "last_name": "Rajib", "name": null }, { "creator_type": "author", "first_name": "Yuichi", "last_name": "Matsuo", "name": null }, { "creator_type": "author", "first_name": "Linh Manh", "last_name": "Ha", "name": null }, { "creator_type": "author", "first_name": "Samandram Sushilkumar", "last_name": "Singh", "name": null }, { "creator_type": "author", "first_name": "Tetsuo", "last_name": "Yamashita", "name": null }, { "creator_type": "author", "first_name": "Euki", "last_name": "Yazaki", "name": null }, { "creator_type": "author", "first_name": "Endah Dwi", "last_name": "Hartuti", "name": null }, { "creator_type": "author", "first_name": "Tetsuro", "last_name": "Matsunaga", "name": null }, { "creator_type": "author", "first_name": "Tomoaki", "last_name": "Ida", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Nozaki", "name": null }, { "creator_type": "author", "first_name": "Takaaki", "last_name": "Akaike", "name": null }, { "creator_type": "author", "first_name": "Tomoo", "last_name": "Shiba", "name": null }, { "creator_type": "author", "first_name": "Jun-Ichi", "last_name": "Kishikawa", "name": null }, { "creator_type": "author", "first_name": "Shinjiro", "last_name": "Hamano", "name": null }, { "creator_type": "author", "first_name": "Kiyoshi", "last_name": "Kita", "name": null }, { "creator_type": "author", "first_name": "Daniel Ken", "last_name": "Inaoka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.freeradbiomed.2026.01.063" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "41638445" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Electron Transport", "descriptor_ui": "D004579", "major_topic": false }, { "descriptor": "Helminth Proteins", "descriptor_ui": "D015801", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mitochondria", "descriptor_ui": "D008928", "major_topic": false }, { "descriptor": "Oxidation-Reduction", "descriptor_ui": "D010084", "major_topic": false }, { "descriptor": "Quinone Reductases", "descriptor_ui": "D011808", "major_topic": true }, { "descriptor": "Schistosoma mansoni", "descriptor_ui": "D012550", "major_topic": true }, { "descriptor": "Sulfides", "descriptor_ui": "D013440", "major_topic": true } ], "publication": { "conference_name": null, "date": "2026 Feb 2", "date_precision": "day", "issue": "", "normalized_date": "2026-02-02", "pages": "646-659", "proceedings_title": null, "publisher": "", "title": "Free radical biology & medicine", "volume": "246", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "Distinct quaternary reaction behavior and stable charge-transfer complex formation in Schistosoma mansoni sulfide:quinone oxidoreductase.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: Metabolic dysfunction-associated steatotic liver disease (MASLD) and its progressive form, metabolic dysfunction-associated steatohepatitis, are highly prevalent and lack effective pharmacotherapies. Hepatocellular lipotoxicity-driven by the accumulation of saturated fatty acids (eg, palmitate)-promotes disease progression; however, the determinants of hepatocyte susceptibility remain incompletely defined. METHODS: We performed a genome-wide CRISPR-Cas9 loss-of-function screening to identify the regulators of palmitate-induced lipotoxicity. The top candidates were validated using genetic perturbation and pharmacological inhibition. Lipid handling, endoplasmic reticulum/oxidative stress, apoptosis, and lipogenic transcriptional programs were also quantified. Human MASLD liver tissues were analyzed for ACSL3 expression in relation to histology and aminotransferases. Single-cell and spatial transcriptomics were used to localize ACSL3 expression and the associated pathway signatures in metabolic dysfunction-associated steatohepatitis. RESULTS: The screen recovered established mediators (CASPASE-8, AGPAT9, RNF213) and identified ACSL3 as a novel determinant of hepatocyte survival under lipotoxic stress. Genetic deletion or pharmacological inhibition of ACSL3 renders hepatocytes resistant to palmitate-induced apoptosis and endoplasmic reticulum stress, accompanied by reduced lipid-droplet accumulation, decreased incorporation of saturated fatty acids into neutral lipids and phospholipids, and blunted induction of lipogenic programs. In human MASLD, hepatic ACSL3 expression positively correlated with histological severity and aminotransferase levels. Single-cell transcriptomics localized ACSL3 predominantly to hepatocytes in advanced metabolic dysfunction-associated steatohepatitis displaying oxidative and endoplasmic reticulum stress signatures, whereas spatial transcriptomics showed ACSL3-high hepatocyte regions enriched for apoptotic and inflammatory pathways and spatially coupled to macrophage-rich and plasma cell-rich niches. CONCLUSIONS: ACSL3 is a central regulator of lipotoxic hepatocyte injury and MASLD progression, mechanistically linking lipid-droplet biogenesis to apoptosis and inflammatory niche formation. These data suggest that ACSL3 is a promising therapeutic target and support further translational studies to evaluate ACSL3 modulation in steatotic liver disease.", "classifications": [ { "id": "Yusa", "label": "Group Yusa", "parent": "Eiraku", "type": "group" }, { "id": "Eiraku", "label": "Team Eiraku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yuta", "last_name": "Myojin", "name": null }, { "creator_type": "author", "first_name": "Takahiro", "last_name": "Kodama", "name": null }, { "creator_type": "author", "first_name": "Ryo", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Hideharu", "last_name": "Nagasawa", "name": null }, { "creator_type": "author", "first_name": "Yasuteru", "last_name": "Kondo", "name": null }, { "creator_type": "author", "first_name": "Kosuke", "last_name": "Yusa", "name": null }, { "creator_type": "author", "first_name": "Tomomi", "last_name": "Yoshida-Hashidate", "name": null }, { "creator_type": "author", "first_name": "Hideo", "last_name": "Shindou", "name": null }, { "creator_type": "author", "first_name": "Kunimaro", "last_name": "Furuta", "name": null }, { "creator_type": "author", "first_name": "Kazuhiro", "last_name": "Murai", "name": null }, { "creator_type": "author", "first_name": "Yoshinobu", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Hayato", "last_name": "Hikita", "name": null }, { "creator_type": "author", "first_name": "Tetsuo", "last_name": "Takehara", "name": null } ], "identifiers": { "doi": { "normalized": "10.1097/hc9.0000000000000884" }, "pmcid": { "normalized": "PMC12826143" }, "pmid": { "normalized": "41564380" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Apoptosis", "descriptor_ui": "D017209", "major_topic": false }, { "descriptor": "Coenzyme A Ligases", "descriptor_ui": "D003066", "major_topic": true }, { "descriptor": "CRISPR-Cas Systems", "descriptor_ui": "D064113", "major_topic": false }, { "descriptor": "Disease Progression", "descriptor_ui": "D018450", "major_topic": false }, { "descriptor": "Endoplasmic Reticulum Stress", "descriptor_ui": "D059865", "major_topic": false }, { "descriptor": "Fatty Liver", "descriptor_ui": "D005234", "major_topic": true }, { "descriptor": "Hepatocytes", "descriptor_ui": "D022781", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Lipid Metabolism", "descriptor_ui": "D050356", "major_topic": false }, { "descriptor": "Liver", "descriptor_ui": "D008099", "major_topic": false }, { "descriptor": "Long-Chain-Fatty-Acid-CoA Ligase", "descriptor_ui": "D000098859", "major_topic": false }, { "descriptor": "Non-alcoholic Fatty Liver Disease", "descriptor_ui": "D065626", "major_topic": true }, { "descriptor": "Oxidative Stress", "descriptor_ui": "D018384", "major_topic": false }, { "descriptor": "Palmitates", "descriptor_ui": "D010168", "major_topic": false } ], "publication": { "conference_name": null, "date": "2026 Feb 1", "date_precision": "day", "issue": "2", "normalized_date": "2026-02-01", "pages": "", "proceedings_title": null, "publisher": "", "title": "Hepatology communications", "volume": "10", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "Genome-wide CRISPR screen identifies ACSL3 as a regulator of lipotoxicity and progression of MASLD.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Wagyu beef's distinctive flavor and tenderness arise from its high levels of unsaturated intramuscular triglycerides. Although these compositional distinctions provide a unique Raman signature, extensive band overlap and background attenuation from packaging and frozen conditions hinder reliable in situ classification and constrain the interpretability of raw spectra. This study presents a label-free Raman spectroscopic and chemometric approach for authenticating Wagyu beef under realistic retail-like conditions. A supervised partial least squares discriminant analysis (PLS-DA) model was developed using spectra from unwrapped adipose tissue and evaluated with an independent validation set of frozen, plastic-wrapped samples from multiple breeds and suppliers. The model achieved 100% sample-level classification accuracy, supported by receiver operating characteristic and confusion-matrix analyses. To elucidate the molecular basis of discrimination and resolve spectral congestion, a two-stage decomposition combining singular value decomposition (SVD) and nonnegative matrix factorization (NMF) was applied, followed by nonnegative least squares (NNLS) fitting with pure triglyceride standards. The analyses yielded chemically interpretable components, revealing enrichment of unsaturated triglycerides in Wagyu beef consistent with established compositional data. To our knowledge, this is the first report applying Raman-based PLS-DA for Wagyu authentication and integrating SVD, NMF, and NNLS for molecular-level interpretation in food authentication. Overall, Raman spectroscopy integrated with interpretable spectral decomposition provides a rapid, nondestructive, and chemically transparent tool for meat authentication and quality assurance.", "classifications": [ { "id": "Nakabayashi", "label": "Group Nakabayashi", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Jia-En", "last_name": "Kao", "name": null }, { "creator_type": "author", "first_name": "Chang-Chun", "last_name": "Li", "name": null }, { "creator_type": "author", "first_name": "Ming-Syue", "last_name": "Lin", "name": null }, { "creator_type": "author", "first_name": "Kohei", "last_name": "Yokosawa", "name": null }, { "creator_type": "author", "first_name": "Takakazu", "last_name": "Nakabayashi", "name": null }, { "creator_type": "author", "first_name": "Tai-Sheng", "last_name": "Yeh", "name": null }, { "creator_type": "author", "first_name": "Ian", "last_name": "Liau", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.talanta.2026.129460" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "41650921" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cattle", "descriptor_ui": "D002417", "major_topic": false }, { "descriptor": "Discriminant Analysis", "descriptor_ui": "D016002", "major_topic": false }, { "descriptor": "Food Packaging", "descriptor_ui": "D018857", "major_topic": true }, { "descriptor": "Least-Squares Analysis", "descriptor_ui": "D016018", "major_topic": false }, { "descriptor": "Meat", "descriptor_ui": "D008460", "major_topic": true }, { "descriptor": "Red Meat", "descriptor_ui": "D000069466", "major_topic": true }, { "descriptor": "Spectrum Analysis, Raman", "descriptor_ui": "D013059", "major_topic": true }, { "descriptor": "Triglycerides", "descriptor_ui": "D014280", "major_topic": true } ], "publication": { "conference_name": null, "date": "2026 Jan 31", "date_precision": "day", "issue": "", "normalized_date": "2026-01-31", "pages": "129460", "proceedings_title": null, "publisher": "", "title": "Talanta", "volume": "303", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "Label-free Raman chemometric analysis for in situ authentication and molecular profiling of Wagyu beef under retail packaging.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Rare diseases are often difficult to diagnose, and their scarcity also makes it challenging to develop deep learning models for them due to limited large-scale datasets. Anterior mediastinal tumors-including thymoma and thymic carcinoma-represent such rare entities. A few diagnostic support systems for these tumors have been proposed; however, no prior studies have tested them across multiple institutions, and clinically applicable and generalizable models remain lacking. A total of 711 computed tomography (CT) images were collected from 136 hospitals, each from a different patient with pathologically proven anterior mediastinal tumors (339 males, 372 females). Of these, 485 images were used for training, 62 for tuning, and 164 for external testing. The external testing dataset comprised CT images from 121 unique institutions not involved in the other datasets. A 3D U-Net-based model was trained on the training dataset, and the model with the best performance on the tuning dataset was selected. This model was then evaluated on the external testing dataset for its segmentation and detection performance across different institutions. Based on the reference standards provided by board-certified diagnostic radiologists, the trained model achieved average Dice scores of 0.82, Intersection over Union (IoU) of 0.72, Precision of 0.85, and Recall of 0.82 for tumor segmentation at the CT-image level. The free-response receiver operating characteristic curve-derived from lesion-wise IoU thresholds-demonstrated high sensitivity and a low false-positive rate for tumor detection. Even under a stricter IoU threshold of 0.50, the model maintained a sensitivity of 0.87 with only 0.61 false positives per scan. Our model achieved clinically applicable segmentation and detection performance for anterior mediastinal tumors, demonstrating broad generalizability across 121 institutions and overcoming the data-scarcity challenges inherent to such rare diseases.", "classifications": [ { "id": "Hamamoto", "label": "Group Hamamoto", "parent": "Okamoto", "type": "group" }, { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Chihiro", "last_name": "Takemura", "name": null }, { "creator_type": "author", "first_name": "Mototaka", "last_name": "Miyake", "name": null }, { "creator_type": "author", "first_name": "Kazuma", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Hiromi", "last_name": "Matsumoto", "name": null }, { "creator_type": "author", "first_name": "Ryota", "last_name": "Shibaki", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Urikura", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Goto", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null }, { "creator_type": "author", "first_name": "Shun-Ichi", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Miyuki", "last_name": "Sone", "name": null }, { "creator_type": "author", "first_name": "Masahiko", "last_name": "Kusumoto", "name": null }, { "creator_type": "author", "first_name": "Ryuji", "last_name": "Hamamoto", "name": null }, { "creator_type": "author", "first_name": "Hirokazu", "last_name": "Watanabe", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41598-026-37504-z" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "41617892" } }, "mesh": [ { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Deep Learning", "descriptor_ui": "D000077321", "major_topic": true }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mediastinal Neoplasms", "descriptor_ui": "D008479", "major_topic": true }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Tomography, X-Ray Computed", "descriptor_ui": "D014057", "major_topic": true } ], "publication": { "conference_name": null, "date": "2026 Jan 30", "date_precision": "day", "issue": "", "normalized_date": "2026-01-30", "pages": "", "proceedings_title": null, "publisher": "", "title": "Scientific reports", "volume": "", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "A clinically applicable and generalizable deep learning model for anterior mediastinal tumors in CT images across multiple institutions.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Cardiac fibroblasts (CFs) are the predominant non-myocyte cell type in the heart and play central roles in extracellular matrix remodeling and intercellular signaling during cardiac physiology and pathology. However, the bioenergetic basis underlying CF functions remains poorly understood, mainly due to the lack of tools for visualizing intracellular adenosine triphosphate (ATP) dynamics with high spatiotemporal resolution. Here, we established immortalized murine cardiac fibroblasts stably expressing the genetically encoded ATP indicator GO-ATeam2 based on Forster Resonance Energy Transfer (FRET). The resulting CF7/GO-ATeam2 cell line allows real-time and quantitative monitoring of cytosolic ATP levels in living cells. CF7/GO-ATeam2 cells exhibited robust proliferation and quick responses to change of cytosolic ATP level. We demonstrated dynamic cytosolic ATP imaging upon pharmacological perturbations of oxidative phosphorylation and glycolysis, as well as under growth factor stimulation. Our work provides the CF7/GO-ATeam2 platform, a versatile cellular resource for dissecting the metabolic regulation of cardiac fibroblasts, offering new opportunities to explore energy dynamics in cardiac physiology and disease.", "classifications": [ { "id": "Kuchimaru", "label": "Group Kuchimaru", "parent": "Shintaku", "type": "group" }, { "id": "Shintaku", "label": "Team Shintaku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Ariunbold", "last_name": "Chuluun-Erdene", "name": null }, { "creator_type": "author", "first_name": "Takahiro", "last_name": "Kuchimaru", "name": null }, { "creator_type": "author", "first_name": "Takayuki", "last_name": "Isagawa", "name": null }, { "creator_type": "author", "first_name": "Tatsuyuki", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Hiroki", "last_name": "Sugimoto", "name": null }, { "creator_type": "author", "first_name": "Kazutoshi", "last_name": "Ono", "name": null }, { "creator_type": "author", "first_name": "Daigo", "last_name": "Sawaki", "name": null }, { "creator_type": "author", "first_name": "Shigeru", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Masamichi", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Norihiko", "last_name": "Takeda", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.bbrc.2026.153377" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "41643553" } }, "mesh": [ { "descriptor": "Adenosine Triphosphate", "descriptor_ui": "D000255", "major_topic": true }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "Cytosol", "descriptor_ui": "D003600", "major_topic": true }, { "descriptor": "Fibroblasts", "descriptor_ui": "D005347", "major_topic": true }, { "descriptor": "Fluorescence Resonance Energy Transfer", "descriptor_ui": "D031541", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Myocardium", "descriptor_ui": "D009206", "major_topic": true } ], "publication": { "conference_name": null, "date": "2026 Jan 29", "date_precision": "day", "issue": "", "normalized_date": "2026-01-29", "pages": "153377", "proceedings_title": null, "publisher": "", "title": "Biochemical and biophysical research communications", "volume": "805", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "Establishment of immortalized murine cardiac fibroblasts for visualizing cytosolic ATP dynamics with a genetically encoded optical indicator.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Somatic Sertoli cells in the seminiferous tubule provide structural and paracrine support for spermatogenesis. Proper regulation of Sertoli cell cytoskeleton dynamics is essential for this function; however, the regulatory mechanisms remain unclear. Here, we found that polypyrimidine tract-binding protein 1 (PTBP1) maintained cytoskeletal integrity in Sertoli cells via mTORC2 signaling. Sertoli cell-specific Ptbp1 deletion in mice resulted in germ cell loss, blood-testis barrier disruption, and male infertility. Transcriptomic analysis of purified Sertoli cells revealed the dysregulation of cytoskeletal and adhesion-related genes. RNA immunoprecipitation sequencing demonstrated that PTBP1 bound to Rictor mRNA. PTBP1 loss reduced RICTOR protein expression and downstream PKCalpha activation, impairing the F-actin cytoskeleton. Cytoskeletal defects caused by PTBP1 deficiency were restored by constitutively active PKCalpha, confirming the functional relevance of the mTORC2-PKCalpha axis. These findings highlighted PTBP1's role as a post-transcriptional regulator of male fertility through the maintenance of Sertoli cell architecture and spermatogenesis.", "classifications": [ { "id": "Yamamoto", "label": "Group Yamamoto", "parent": "Toyoshima", "type": "group" }, { "id": "Toyoshima", "label": "Team Toyoshima", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Manabu", "last_name": "Ozawa", "name": null }, { "creator_type": "author", "first_name": "Jumpei", "last_name": "Taguchi", "name": null }, { "creator_type": "author", "first_name": "Hideto", "last_name": "Mori", "name": null }, { "creator_type": "author", "first_name": "Mio", "last_name": "Kikuchi", "name": null }, { "creator_type": "author", "first_name": "Masafumi", "last_name": "Muratani", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Yasuhiro", "last_name": "Yamada", "name": null }, { "creator_type": "author", "first_name": "Nobuaki", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Masahito", "last_name": "Ikawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s42003-026-09636-5" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "41612039" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Blood-Testis Barrier", "descriptor_ui": "D001814", "major_topic": false }, { "descriptor": "Cytoskeleton", "descriptor_ui": "D003599", "major_topic": true }, { "descriptor": "Heterogeneous-Nuclear Ribonucleoproteins", "descriptor_ui": "D034441", "major_topic": true }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mechanistic Target of Rapamycin Complex 2", "descriptor_ui": "D000076225", "major_topic": true }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Polypyrimidine Tract-Binding Protein", "descriptor_ui": "D038941", "major_topic": true }, { "descriptor": "Protein Kinase C-alpha", "descriptor_ui": "D051571", "major_topic": true }, { "descriptor": "Rapamycin-Insensitive Companion of mTOR Protein", "descriptor_ui": "D000076226", "major_topic": false }, { "descriptor": "Sertoli Cells", "descriptor_ui": "D012708", "major_topic": true }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Spermatogenesis", "descriptor_ui": "D013091", "major_topic": true } ], "publication": { "conference_name": null, "date": "2026 Jan 29", "date_precision": "day", "issue": "", "normalized_date": "2026-01-29", "pages": "", "proceedings_title": null, "publisher": "", "title": "Communications biology", "volume": "", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "PTBP1 supports mouse spermatogenesis by facilitating cytoskeletal organization through the mTORC2-PKCalpha pathway in Sertoli cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "OBJECTIVE: Understanding the discordance between RNA and protein expression can help elucidate underlying disease mechanisms that cannot be fully explained using transcriptomic information alone. Unveiling novel mechanisms of tumorigenesis through multi-omics data using real-world data is central to advancing precision in oncology and tumor prevention. In this study, we investigated the expression discordance between non-tumor and tumor patient samples to elucidate the underlying mechanism of tumorigenesis in lung adenocarcinoma (LUAD). METHODS: We performed a correlation analysis of RNA and protein using normal tissue adjacent to tumor and tumor samples to identify distinct expression profiles to unveil tumorigenesis. Publicly available multi-omics data, including RNA, proteins, phosphoproteins, and acetyl proteins, were obtained from the Clinical Proteomic Tumor Analysis Consortium. Gene expression analysis at the single-cell level was performed using single-cell RNA sequencing data. A transformer model was used for in silico drug screening. RESULTS: Most genes in tumors showed a positive correlation between RNA and protein expression. DNA topoisomerase II alpha (TOP2A) and Cyclin-dependent kinase 1 showed a drastic correlation during tumorigenesis in patient with LUAD. TOP2A gene and protein expression were associated with overall survival in patients with LUAD. Single-cell RNA sequencing revealed that highly correlated genes were clustered as distinct subpopulations. TOP2A expression was associated with TP53 genomic status and miR-26A1 expression, which targets TOP2A gene. In silico screening identified novel drugs that could specifically target TOP2A. CONCLUSIONS: Our findings elucidated the multi-layer expression profiles of LUAD, revealing its tumorigenesis and potential clinical implications and interventions. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12672-026-04470-x.", "classifications": [ { "id": "Hamamoto", "label": "Group Hamamoto", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Mika", "last_name": "Miyabe", "name": null }, { "creator_type": "author", "first_name": "Shuntaro", "last_name": "Arimitsu", "name": null }, { "creator_type": "author", "first_name": "Amina", "last_name": "Bolatkan", "name": null }, { "creator_type": "author", "first_name": "Hidenori", "last_name": "Machino", "name": null }, { "creator_type": "author", "first_name": "Ryuji", "last_name": "Hamamoto", "name": null }, { "creator_type": "author", "first_name": "Ken", "last_name": "Asada", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/s12672-026-04470-x" }, "pmcid": { "normalized": "PMC12852518" }, "pmid": { "normalized": "41604018" } }, "mesh": [], "publication": { "conference_name": null, "date": "2026 Jan 28", "date_precision": "day", "issue": "1", "normalized_date": "2026-01-28", "pages": "170", "proceedings_title": null, "publisher": "", "title": "Discover oncology", "volume": "17", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "Deciphering RNA and protein expression discordance identifies TOP2A as a prognostic biomarker and potential therapeutic target in lung adenocarcinoma.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Fibroblast growth factor-23 (FGF23) is a bone-derived hormone that promotes urinary phosphate excretion in response to phosphate loading. While essential for phosphate homeostasis, elevated FGF23 increases phosphate concentration in the renal tubular fluid, promoting calcium-phosphate crystal formation and tubular injury. Here we show that bone resorption mobilizes phosphate into the circulation and mimics the pathophysiology of dietary phosphate loading. Enhanced bone resorption, induced by soluble receptor activator of NF-kappaB ligand (sRANKL) administration or microgravity exposure on the International Space Station, increased circulating FGF23 levels and caused renal tubular injury in mice. Pre-treatment with bisphosphonate, an inducer of osteoclast apoptosis, prevented sRANKL-induced increases in FGF23 and tubular damage. These findings suggest that bone mineral loss may contribute to renal tubular injury in clinical settings, including immobilization, osteoporosis, and chronic kidney disease-mineral bone disorder.", "classifications": [ { "id": "Kuchimaru", "label": "Group Kuchimaru", "parent": "Shintaku", "type": "group" }, { "id": "Shintaku", "label": "Team Shintaku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Hirosaka", "last_name": "Hayashi", "name": null }, { "creator_type": "author", "first_name": "Yutaka", "last_name": "Miura", "name": null }, { "creator_type": "author", "first_name": "Yoshitaka", "last_name": "Iwazu", "name": null }, { "creator_type": "author", "first_name": "Hideyuki", "last_name": "Mukai", "name": null }, { "creator_type": "author", "first_name": "Yoshiyuki", "last_name": "Mori", "name": null }, { "creator_type": "author", "first_name": "Takahiro", "last_name": "Kuchimaru", "name": null }, { "creator_type": "author", "first_name": "Nobuhiko", "last_name": "Ohno", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Aiba", "name": null }, { "creator_type": "author", "first_name": "Risa", "last_name": "Okada", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Kamimura", "name": null }, { "creator_type": "author", "first_name": "Dai", "last_name": "Shiba", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Kurosu", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Kuro-O", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s42003-026-09603-0" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "41571870" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Bone Resorption", "descriptor_ui": "D001862", "major_topic": true }, { "descriptor": "Fibroblast Growth Factor-23", "descriptor_ui": "D000089703", "major_topic": false }, { "descriptor": "Fibroblast Growth Factors", "descriptor_ui": "D005346", "major_topic": false }, { "descriptor": "Kidney Tubules", "descriptor_ui": "D007684", "major_topic": true }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Phosphates", "descriptor_ui": "D010710", "major_topic": false }, { "descriptor": "RANK Ligand", "descriptor_ui": "D053245", "major_topic": false }, { "descriptor": "Weightlessness", "descriptor_ui": "D014893", "major_topic": false } ], "publication": { "conference_name": null, "date": "2026 Jan 22", "date_precision": "day", "issue": "", "normalized_date": "2026-01-22", "pages": "", "proceedings_title": null, "publisher": "", "title": "Communications biology", "volume": "", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "Bone mineral loss damages renal tubules in mice.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: PREDICT is a prognostic tool developed in the United Kingdom to estimate postoperative overall survival (OS) and the additional benefits of adjuvant therapies in patients with breast cancer. It has been validated in various international cohorts and continuously updated with the inclusion of new variables and model retraining. However, their efficacy in the Japanese population remains unclear. We aimed to evaluate the generalizability of PREDICT versions 2.2 (v2.2) and 3.0 (v3.0) using data from the National Cancer Center Hospital in Japan, a high-volume cancer center. METHODS: We analyzed a retrospective cohort (2006-2016) including 2,980 cases of postoperative breast cancer. We calculated survival predictions using both v2.2 and v3.0, and compared them with the Kaplan-Meier-estimated survival probabilities using a calibration plot. Additionally, we performed a time-dependent receiver operating characteristic (ROC) curve analysis for v2.2 and v3.0. RESULTS: Both models tended to underestimate survival in our cohort, whereas v3.0 showed improved calibration compared to v2.2, for 5- and 10-year OS. Both v2.2 and v3.0 maintained good discriminative performance throughout 10 years, with values under the ROC curve generally above 0.80. CONCLUSIONS: Despite these differences, both versions demonstrated satisfactory performance, suggesting that they can be generalized for Japanese patients with postoperative breast cancer. Notably, v3.0, given its improved calibration, might be more suitable for supporting shared decision making. The model's performance in predicting 5-year OS supports its generalizability, whereas 10-year projections warrant caution due to limited follow-up. Overall, this study demonstrates that PREDICT is a valuable prognostic tool for Japanese patients with breast cancer.", "classifications": [ { "id": "Hamamoto", "label": "Group Hamamoto", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Hiromi", "last_name": "Hashiguchi", "name": null }, { "creator_type": "author", "first_name": "Nobuji", "last_name": "Kouno", "name": null }, { "creator_type": "author", "first_name": "Masaaki", "last_name": "Komatsu", "name": null }, { "creator_type": "author", "first_name": "Sho", "last_name": "Shiino", "name": null }, { "creator_type": "author", "first_name": "Naoto", "last_name": "Takehara", "name": null }, { "creator_type": "author", "first_name": "Katsuji", "last_name": "Takeda", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Yi-Wen", "last_name": "Hsiao", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Murata", "name": null }, { "creator_type": "author", "first_name": "Kazutaka", "last_name": "Obama", "name": null }, { "creator_type": "author", "first_name": "Shin", "last_name": "Takayama", "name": null }, { "creator_type": "author", "first_name": "Paul D. P.", "last_name": "Pharoah", "name": null }, { "creator_type": "author", "first_name": "Ryuji", "last_name": "Hamamoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/s12282-026-01823-w" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "41553642" } }, "mesh": [ { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Breast Neoplasms", "descriptor_ui": "D001943", "major_topic": true }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Japan", "descriptor_ui": "D007564", "major_topic": false }, { "descriptor": "Kaplan-Meier Estimate", "descriptor_ui": "D053208", "major_topic": false }, { "descriptor": "Mastectomy", "descriptor_ui": "D008408", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Postoperative Period", "descriptor_ui": "D011184", "major_topic": false }, { "descriptor": "Prognosis", "descriptor_ui": "D011379", "major_topic": false }, { "descriptor": "Retrospective Studies", "descriptor_ui": "D012189", "major_topic": false }, { "descriptor": "ROC Curve", "descriptor_ui": "D012372", "major_topic": false } ], "publication": { "conference_name": null, "date": "2026 Jan 19", "date_precision": "day", "issue": "", "normalized_date": "2026-01-19", "pages": "", "proceedings_title": null, "publisher": "", "title": "Breast cancer (Tokyo, Japan)", "volume": "", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "Validation of the postoperative prognostication tool PREDICT version 2.2 and 3.0 using data from the National cancer center hospital in Japan.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The development of cognitive functions continues into adolescence. However, it is not fully understood how cortical circuitry changes during adolescence. Here, we performed a comprehensive super-resolution mapping of dendritic spines in layer 5 extratelencepharic-projecting (L5 ET) neurons in the primary somatosensory cortex in mice. In adults, the dendritic spines are highly enriched in the middle compartment of the apical dendrites (spine density \"hotspot\"), where dendritic calcium spikes are generated. In early development, dendritic spines are evenly distributed. During adolescence, however, the spine density increases specifically in the middle compartment of the apical dendrites in an experience-dependent manner, while other dendritic compartments show a slight reduction. Furthermore, spine accumulation at the hotspot was specifically impaired in mouse models of schizophrenia, demonstrating a link between adolescent spine formation and neuropsychiatric disorders. Our finding suggests that the dendritic compartment-specific spine formation during adolescence shapes nonlinear dendritic integration in L5 ET neurons and supports the maturation of cognitive functions.", "classifications": [ { "id": "JPMJCR2021", "label": "JPMJCR2021", "researcher": "Hideki Enomoto", "type": "grant" }, { "id": "Enomoto", "label": "Group Enomoto", "parent": "Enomoto", "type": "group" }, { "id": "Imai", "label": "Group Imai", "parent": "Enomoto", "type": "group" }, { "id": "Enomoto", "label": "Team Enomoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Ryo", "last_name": "Egashira", "name": null }, { "creator_type": "author", "first_name": "Meng-Tsen", "last_name": "Ke", "name": null }, { "creator_type": "author", "first_name": "Nao", "last_name": "Nakagawa-Tamagawa", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Fujimoto", "name": null }, { "creator_type": "author", "first_name": "Shigenori", "last_name": "Inagaki", "name": null }, { "creator_type": "author", "first_name": "Tsuyoshi", "last_name": "Takagi", "name": null }, { "creator_type": "author", "first_name": "Tsuyoshi", "last_name": "Miyakawa", "name": null }, { "creator_type": "author", "first_name": "Yoshiaki", "last_name": "Tagawa", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Imai", "name": null } ], "identifiers": { "doi": { "normalized": "10.1126/sciadv.adw8458" }, "pmcid": { "normalized": "PMC12802838" }, "pmid": { "normalized": "41533795" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Dendrites", "descriptor_ui": "D003712", "major_topic": false }, { "descriptor": "Dendritic Spines", "descriptor_ui": "D049229", "major_topic": true }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Neurodevelopment", "descriptor_ui": "D000099203", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": true }, { "descriptor": "Schizophrenia", "descriptor_ui": "D012559", "major_topic": false }, { "descriptor": "Somatosensory Cortex", "descriptor_ui": "D013003", "major_topic": true } ], "publication": { "conference_name": null, "date": "2026 Jan 16", "date_precision": "day", "issue": "3", "normalized_date": "2026-01-16", "pages": "eadw8458", "proceedings_title": null, "publisher": "", "title": "Science advances", "volume": "12", "year": 2026 }, "ssbd": { "database": [], "repository": [ "ssbd-repos-000429" ] }, "title": "Dendritic compartment-specific spine formation in layer 5 neurons underlies cortical circuit maturation during adolescence.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: Impaired glucose homeostasis leads to numerous complications, with coronary artery disease (CAD) being a major contributor to healthcare costs worldwide. Because continuous glucose monitoring (CGM) captures multidimensional features of glucose regulation beyond average glycemia, we evaluated whether CGM-derived indices better predict coronary plaque vulnerability than conventional measures. METHODS: We examined associations between CGM-derived indices and coronary plaque vulnerability assessed by virtual histology-intravascular ultrasound, focusing on the necrotic core (%NC) in humans. We analyzed 14 CGM-derived indices, including average daily risk ratio (ADRR) and autocorrelation-based metrics (AC_Mean and AC_Var), alongside commonly used measures, such as fasting blood glucose (FBG), hemoglobin A1c (HbA1c), and 120 min plasma glucose during oral glucose tolerance testing (PG120). Factor analysis was used to identify latent components underlying glucose dynamics and to relate these components to %NC. Findings were validated across independent datasets from Japan (n=64), the United States (n=53), and China (n=100). RESULTS: CGM-derived indices, particularly ADRR and AC_Var, demonstrated stronger predictive capability for %NC than FBG, HbA1c, and PG120. Factor analysis identified three independent components of glucose dynamics: mean, variance, and autocorrelation, each showing an independent association with %NC. ADRR reflected both mean and variance components, whereas AC_Var primarily captured the autocorrelation component. In contrast, FBG, HbA1c, and PG120 primarily reflected the mean component alone and were, therefore, insufficient for %NC prediction. CONCLUSIONS: CGM-derived indices reflecting the three components of glucose dynamics can serve as more effective screening tools for CAD risk assessment, complementing or possibly replacing traditional diabetes diagnostic methods. FUNDING: This study was supported by the Japan Society for the Promotion of Science (JSPS) KAKENHI (JP21H04759), CREST, the Japan Science and Technology Agency (JST) (JPMJCR2123), The Uehara Memorial Foundation, and The Takeda Science Foundation.", "classifications": [ { "id": "JPMJCR2123", "label": "JPMJCR2123", "researcher": "Shinya Kuroda", "type": "grant" }, { "id": "Kuroda", "label": "Group Kuroda", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Hikaru", "last_name": "Sugimoto", "name": null }, { "creator_type": "author", "first_name": "Ken-Ichi", "last_name": "Hironaka", "name": null }, { "creator_type": "author", "first_name": "Tomoko", "last_name": "Yamada", "name": null }, { "creator_type": "author", "first_name": "Natsu", "last_name": "Otowa-Suematsu", "name": null }, { "creator_type": "author", "first_name": "Yushi", "last_name": "Hirota", "name": null }, { "creator_type": "author", "first_name": "Hiromasa", "last_name": "Otake", "name": null }, { "creator_type": "author", "first_name": "Ken-Ichi", "last_name": "Hirata", "name": null }, { "creator_type": "author", "first_name": "Kazuhiko", "last_name": "Sakaguchi", "name": null }, { "creator_type": "author", "first_name": "Wataru", "last_name": "Ogawa", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Kuroda", "name": null } ], "identifiers": { "doi": { "normalized": "10.7554/elife.102860" }, "pmcid": { "normalized": "PMC12807456" }, "pmid": { "normalized": "41537426" } }, "mesh": [ { "descriptor": "Blood Glucose", "descriptor_ui": "D001786", "major_topic": true }, { "descriptor": "China", "descriptor_ui": "D002681", "major_topic": false }, { "descriptor": "Continuous Glucose Monitoring", "descriptor_ui": "D000095583", "major_topic": true }, { "descriptor": "Coronary Artery Disease", "descriptor_ui": "D003324", "major_topic": true }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Glycated Hemoglobin", "descriptor_ui": "D006442", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Japan", "descriptor_ui": "D007564", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Plaque, Atherosclerotic", "descriptor_ui": "D058226", "major_topic": true }, { "descriptor": "Retrospective Studies", "descriptor_ui": "D012189", "major_topic": false }, { "descriptor": "United States", "descriptor_ui": "D014481", "major_topic": false } ], "publication": { "conference_name": null, "date": "2026 Jan 15", "date_precision": "day", "issue": "", "normalized_date": "2026-01-15", "pages": "", "proceedings_title": null, "publisher": "", "title": "eLife", "volume": "14", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "Association between continuous glucose monitoring-derived metrics and coronary plaque vulnerability: A retrospective exploratory analysis.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Total anomalous pulmonary venous connection (TAPVC) is one of the most severe congenital heart defects; however, prenatal diagnosis remains suboptimal. A normal fetal heart has a junction between the pulmonary venous (PV) and left atrium (LA). In contrast, no junctions are observed in patients with TAPVC. In the present study, we attempted to visualize and detect fetal PV-LA connections using artificial intelligence (AI) trained on the fetal cardiac ultrasound videos of 100 normal cases and six TAPVC cases. The PV-LA aggregate area was segmented using the following three-dimensional (3D) segmentation models: SegResNet, Swin UNETR, MedNeXt, and SegFormer3D. The Dice coefficient and 95% Hausdorff distance were used to evaluate segmentation performance. The mean values of the shortest PV-LA distance (PLD) and major axis angle (PLA) in each video were calculated. These methods demonstrated sufficient performance in visualizing and detecting the PV-LA connection. In terms of TAPVC screening performance, MedNeXt-PLD and SegResNet-PLA achieved mean area under the receiver operating characteristic curve values of 0.844 and 0.840, respectively. Overall, this study shows that our approach can support unskilled examiners in capturing the PV-LA connection and has the potential to improve the prenatal detection rate of TAPVC.", "classifications": [ { "id": "Hamamoto", "label": "Group Hamamoto", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Reina", "last_name": "Komatsu", "name": null }, { "creator_type": "author", "first_name": "Masaaki", "last_name": "Komatsu", "name": null }, { "creator_type": "author", "first_name": "Katsuji", "last_name": "Takeda", "name": null }, { "creator_type": "author", "first_name": "Naoaki", "last_name": "Harada", "name": null }, { "creator_type": "author", "first_name": "Naoki", "last_name": "Teraya", "name": null }, { "creator_type": "author", "first_name": "Shohei", "last_name": "Wakisaka", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Natsume", "name": null }, { "creator_type": "author", "first_name": "Tomonori", "last_name": "Taniguchi", "name": null }, { "creator_type": "author", "first_name": "Rina", "last_name": "Aoyama", "name": null }, { "creator_type": "author", "first_name": "Mayumi", "last_name": "Kaneko", "name": null }, { "creator_type": "author", "first_name": "Kazuki", "last_name": "Iwamoto", "name": null }, { "creator_type": "author", "first_name": "Ryu", "last_name": "Matsuoka", "name": null }, { "creator_type": "author", "first_name": "Akihiko", "last_name": "Sekizawa", "name": null }, { "creator_type": "author", "first_name": "Ryuji", "last_name": "Hamamoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.3390/bioengineering13010100" }, "pmcid": { "normalized": "PMC12837485" }, "pmid": { "normalized": "41596031" } }, "mesh": [], "publication": { "conference_name": null, "date": "2026 Jan 15", "date_precision": "day", "issue": "1", "normalized_date": "2026-01-15", "pages": "", "proceedings_title": null, "publisher": "", "title": "Bioengineering (Basel, Switzerland)", "volume": "13", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "Three-Dimensional Visualization and Detection of the Pulmonary Venous-Left Atrium Connection Using Artificial Intelligence in Fetal Cardiac Ultrasound Screening.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Dysregulation of hepatokines has been observed in patients with metabolic dysfunction-associated steatotic liver disease (MASLD), suggesting their involvement in disease progression. In this study, we aimed to investigate the role of alpha1-acid glycoprotein (AGP), a hepatokine, in the progression of MASLD, and to evaluate its potential therapeutic utility. Reanalysis of hepatic RNA-seq datasets from patients with fatty liver disease showed that expression of the hepatic AGP gene decreased with disease progression. A high-fat diet (HFD)-induced mouse model of MASLD also showed decreased plasma and hepatic AGP levels. Whole-body AGP-knockout (AGP-KO) mice were fed a HFD for 12 weeks. Compared to wild-type mice, AGP-KO mice fed a HFD displayed further exacerbated hepatic steatosis, obesity, adipose tissue inflammation and impaired glucose tolerance, suggesting a protective role for endogenous AGP against MASLD. Morphological abnormalities of hepatic mitochondria were observed in AGP-KO mice. Human-derived AGP (hAGP) was isolated and purified from plasma fraction V supernatant derived from human blood donations using ion-exchange column chromatography. hAGP exerted a protective effect against palmitate-induced lipotoxicity in hepatocytes, adipocytes and macrophages. Exogenous administration of hAGP to MASLD mice attenuated disease progression by reducing hepatic mitochondrial dysfunction and adipose tissue inflammation. In conclusion, decreased endogenous AGP levels may contribute to the disease progression of MASLD. AGP has the potential to serve as a novel therapeutic agent against MASLD by targeting both liver and adipose tissue.", "classifications": [ { "id": "Nishida", "label": "Group Nishida", "parent": "Nishida", "type": "group" }, { "id": "Nishimura", "label": "Group Nishimura", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Ayano", "last_name": "Nishinoiri", "name": null }, { "creator_type": "author", "first_name": "Kai", "last_name": "Tokumaru", "name": null }, { "creator_type": "author", "first_name": "Gai", "last_name": "Kanazawa", "name": null }, { "creator_type": "author", "first_name": "Yuhi", "last_name": "Shintani", "name": null }, { "creator_type": "author", "first_name": "Takuma", "last_name": "Yoshitake", "name": null }, { "creator_type": "author", "first_name": "Takahiro", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Soyoka", "last_name": "Fukuta", "name": null }, { "creator_type": "author", "first_name": "Akiyuki", "last_name": "Nishimura", "name": null }, { "creator_type": "author", "first_name": "Motohiro", "last_name": "Nishida", "name": null }, { "creator_type": "author", "first_name": "Toru", "last_name": "Takeo", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Maeda", "name": null }, { "creator_type": "author", "first_name": "Toru", "last_name": "Maruyama", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Watanabe", "name": null } ], "identifiers": { "doi": { "normalized": "10.1210/endocr/bqag009" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "41537567" } }, "mesh": [ { "descriptor": "Adipose Tissue", "descriptor_ui": "D000273", "major_topic": true }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Diet, High-Fat", "descriptor_ui": "D059305", "major_topic": false }, { "descriptor": "Disease Progression", "descriptor_ui": "D018450", "major_topic": false }, { "descriptor": "Fatty Liver", "descriptor_ui": "D005234", "major_topic": true }, { "descriptor": "Hepatocytes", "descriptor_ui": "D022781", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Liver", "descriptor_ui": "D008099", "major_topic": true }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Orosomucoid", "descriptor_ui": "D009961", "major_topic": true } ], "publication": { "conference_name": null, "date": "2026 Jan 14", "date_precision": "day", "issue": "", "normalized_date": "2026-01-14", "pages": "bqag009", "proceedings_title": null, "publisher": "", "title": "Endocrinology", "volume": "", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "alpha1-Acid Glycoprotein Mitigates MASLD Progression by Modulating Liver and Adipose Tissue Function.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Transient receptor potential canonical (TRPC) channels function as multimodal cation channels that integrate chemical and mechanical cues to regulate cellular signaling. Among them, TRPC3 and TRPC6 have been studied primarily in the context of cardiovascular and renal physiology, and their roles in other organ systems are now increasingly recognized. Although these channels are known to be activated downstream of phospholipase C (PLC) signaling, especially 1,2-diacylglycerol (DAG) production, their precise modes of activation under native physiological conditions remain incompletely understood. Recent structural and functional studies have greatly advanced our understanding of their primary activation by DAG. This review summarizes how decades of physiological analyses have revealed multiple modes of TRPC3 and TRPC6 channel activation beyond DAG gating, providing a broader perspective on their diverse regulatory mechanisms. This review also highlights recent progress in elucidating the channel properties, activation mechanisms, and the physiological as well as pathophysiological roles of TRPC3 and TRPC6 in cardiovascular contractility and remodeling, and discusses the remaining challenges that will lead to the establishment of TRPC3 and TRPC6 as validated therapeutic targets.", "classifications": [ { "id": "Nishida", "label": "Group Nishida", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Takuro", "last_name": "Numaga-Tomita", "name": null }, { "creator_type": "author", "first_name": "Motohiro", "last_name": "Nishida", "name": null } ], "identifiers": { "doi": { "normalized": "10.3390/cells15020144" }, "pmcid": { "normalized": "PMC12838967" }, "pmid": { "normalized": "41597219" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cardiovascular System", "descriptor_ui": "D002319", "major_topic": true }, { "descriptor": "Diglycerides", "descriptor_ui": "D004075", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Myocardial Contraction", "descriptor_ui": "D009200", "major_topic": true }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "TRPC Cation Channels", "descriptor_ui": "D050052", "major_topic": true }, { "descriptor": "TRPC6 Cation Channel", "descriptor_ui": "D000074287", "major_topic": true } ], "publication": { "conference_name": null, "date": "2026 Jan 14", "date_precision": "day", "issue": "2", "normalized_date": "2026-01-14", "pages": "", "proceedings_title": null, "publisher": "", "title": "Cells", "volume": "15", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "TRPC3 and TRPC6: Multimodal Cation-Conducting Channels Regulating Cardiovascular Contractility and Remodeling.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Hepatic ischemia-reperfusion injury (IRI) is a critical clinical condition associated with liver transplantation and acute liver injury. This study investigated the role of sulfide quinone oxidoreductase (SQOR) and its downstream product, supersulfides, in hepatic IRI. C57BL/6NJ mice were subjected to 45 min of partial hepatic ischemia, followed by reperfusion lasting 4 h. Control of shRNA mediated knockdown of SQOR expressing adeno-associated viral vectors were administered 3 weeks prior to liver ischemia. In the shRNA-mediated knockdown of SQOR group, the hydro-trisulfide donor sodium trisulfide was administered daily for 1 week prior to the induction of liver ischemia. SQOR played a crucial protective role during hepatic IRI by facilitating electron transport to the mitochondrial respiratory chain and maintaining the oxidized and reduced nicotinamide adenine dinucleotide ratio. Administration of sodium trisulfide, exhibited protective effects against hepatic IRI. Sodium trisulfide restored the oxidized and reduced nicotinamide adenine dinucleotide ratio, reduced oxidative stress, and preserved the expression of key enzymes involved in the sulfide oxidation pathway. SQOR and supersulfides contribute to hepatic protection against IRI, likely through their potent antioxidative and redox-regulating functions, and highlight sodium trisulfide as a potential therapeutic agent.", "classifications": [ { "id": "JPMJCR2024", "label": "JPMJCR2024", "researcher": "Motohiro Nishida", "type": "grant" }, { "id": "Akaike", "label": "Group Akaike", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Group Nishida", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Shinnosuke", "last_name": "Takamori", "name": null }, { "creator_type": "author", "first_name": "Kazuhiro", "last_name": "Shirozu", "name": null }, { "creator_type": "author", "first_name": "Eizo", "last_name": "Marutani", "name": null }, { "creator_type": "author", "first_name": "Tsuyoshi", "last_name": "Takata", "name": null }, { "creator_type": "author", "first_name": "Yukie", "last_name": "Mizuta", "name": null }, { "creator_type": "author", "first_name": "Takahito", "last_name": "Kawano", "name": null }, { "creator_type": "author", "first_name": "Masaharu", "last_name": "Murata", "name": null }, { "creator_type": "author", "first_name": "Tomoaki", "last_name": "Ida", "name": null }, { "creator_type": "author", "first_name": "Tetsuro", "last_name": "Matsunaga", "name": null }, { "creator_type": "author", "first_name": "Takaaki", "last_name": "Akaike", "name": null }, { "creator_type": "author", "first_name": "Ken", "last_name": "Yamaura", "name": null }, { "creator_type": "author", "first_name": "Tomohiko", "last_name": "Akahoshi", "name": null } ], "identifiers": { "doi": { "normalized": "10.3390/antiox15010094" }, "pmcid": { "normalized": "PMC12838252" }, "pmid": { "normalized": "41596153" } }, "mesh": [], "publication": { "conference_name": null, "date": "2026 Jan 12", "date_precision": "day", "issue": "1", "normalized_date": "2026-01-12", "pages": "", "proceedings_title": null, "publisher": "", "title": "Antioxidants (Basel, Switzerland)", "volume": "15", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "Role of Sulfide Quinone Oxidoreductase and Supersulfides in Hepatic Ischemia-Reperfusion Injury in Mice.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: Depression represents a major global disease burden. While the Center for Epidemiologic Studies Depression Scale (CES-D) is widely used, it relies on subjective self-reporting. Saliva enables non-invasive metabolite analysis, but existing metabolomics studies have focused on clinical depression using blood or urine, with limited investigation of salivary metabolites in community populations. This study investigated associations between CES-D scores and salivary metabolite concentrations in Tokyo residents. METHODS: This cross-sectional study collected CES-D responses and morning saliva samples from Tokyo residents. Salivary metabolites were analyzed using capillary electrophoresis time-of-flight mass spectrometry. Statistical analyses included permutational multivariate analysis of variance (PERMANOVA) for overall metabolite-CES-D associations, pathway enrichment analysis using fast gene set enrichment analysis (FGSEA), and principal component analysis, adjusted for age and sex. RESULTS: Analysis included 107 participants (40 males, 67 females; mean age 55.3 +/- 14.2 years). PERMANOVA revealed significant association between 112 salivary metabolites and CES-D scores (F = 2.870, p = 0.003), with metabolites explaining 7.7% of depressive symptom variance. Pathway enrichment analysis identified significant alterations in amino acid metabolism (normalized enrichment score =-1.750, q = 0.007). Glycolysis and amine/polyamine metabolism showed trend-level enrichment (both q = 0.066). Principal component analysis revealed significant correlations between CES-D scores and pathway activity for amino acid metabolism (r = 0.216, p = 0.027) and amine/polyamine metabolism (r = 0.216, p = 0.027). CONCLUSION: This study demonstrates significant associations between salivary metabolite profiles and depressive symptoms in a nonclinical community population, with amino acid metabolism emerging as the most robustly altered pathway. These findings provide preliminary evidence for associations between salivary metabolomic profiles and depressive symptoms in a nonclinical community population.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yuri", "last_name": "Kubo", "name": null }, { "creator_type": "author", "first_name": "Futaha", "last_name": "Yamauchi", "name": null }, { "creator_type": "author", "first_name": "Nanase", "last_name": "Goshima", "name": null }, { "creator_type": "author", "first_name": "Maki", "last_name": "Ohishi", "name": null }, { "creator_type": "author", "first_name": "Takanori", "last_name": "Hasegawa", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Masaomi", "last_name": "Ikeda", "name": null }, { "creator_type": "author", "first_name": "Kazuhiro", "last_name": "Aoki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/s44192-025-00363-7" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "41518548" } }, "mesh": [], "publication": { "conference_name": null, "date": "2026 Jan 10", "date_precision": "day", "issue": "", "normalized_date": "2026-01-10", "pages": "", "proceedings_title": null, "publisher": "", "title": "Discover mental health", "volume": "", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "Cross-sectional associations between CES-D scores and the salivary metabolome in nonclinical adults.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Glutathione polysulfides GSSSG and GSSSSG are stable in water up to 80 degrees C and below pH 9. Their carboxyl groups can be efficiently esterified with TMSCl in alcohols, reacting first at glycine, then glutamic acid. The resulting 3-butyne-1-yl esters allow Cu-catalyzed labeling (e.g., biotin, fluorophore) and can be hydrolyzed by esterases.", "classifications": [ { "id": "JPMJCR2024", "label": "JPMJCR2024", "researcher": "Motohiro Nishida", "type": "grant" }, { "id": "Akaike", "label": "Group Akaike", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Group Nishida", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Masana", "last_name": "Yazaki", "name": null }, { "creator_type": "author", "first_name": "Yaozhuo", "last_name": "Zhang", "name": null }, { "creator_type": "author", "first_name": "Lin", "last_name": "Zhou", "name": null }, { "creator_type": "author", "first_name": "Ryo", "last_name": "Morise", "name": null }, { "creator_type": "author", "first_name": "Takaaki", "last_name": "Akaike", "name": null }, { "creator_type": "author", "first_name": "Mieko", "last_name": "Arisawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1039/d5cc07029e" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "41511831" } }, "mesh": [], "publication": { "conference_name": null, "date": "2026 Jan 9", "date_precision": "day", "issue": "", "normalized_date": "2026-01-09", "pages": "", "proceedings_title": null, "publisher": "", "title": "Chemical communications (Cambridge, England)", "volume": "", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "Acid-catalyzed esterification and biotin/fluorescent labeling of glutathione polysulfides based on stability under heating and pH change.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "", "classifications": [ { "id": "Nishikii", "label": "Group Nishikii", "parent": "Shintaku", "type": "group" }, { "id": "Shintaku", "label": "Team Shintaku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yusuke", "last_name": "Kiyoki", "name": null }, { "creator_type": "author", "first_name": "Yumiko", "last_name": "Maruyama", "name": null }, { "creator_type": "author", "first_name": "Yuzuki", "last_name": "Maruyama", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Arai", "name": null }, { "creator_type": "author", "first_name": "Yasuko", "last_name": "Ogino", "name": null }, { "creator_type": "author", "first_name": "Yasuhito", "last_name": "Suehara", "name": null }, { "creator_type": "author", "first_name": "Yuya", "last_name": "Sasaki", "name": null }, { "creator_type": "author", "first_name": "Keiichiro", "last_name": "Hattori", "name": null }, { "creator_type": "author", "first_name": "Tatsuhiro", "last_name": "Sakamoto", "name": null }, { "creator_type": "author", "first_name": "Takayasu", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Naoki", "last_name": "Kurita", "name": null }, { "creator_type": "author", "first_name": "Naoshi", "last_name": "Obara", "name": null }, { "creator_type": "author", "first_name": "Shigeru", "last_name": "Chiba", "name": null }, { "creator_type": "author", "first_name": "Mamiko", "last_name": "Sakata-Yanagimoto", "name": null }, { "creator_type": "author", "first_name": "Hidekazu", "last_name": "Nishikii", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.jtct.2026.01.003" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "41520916" } }, "mesh": [], "publication": { "conference_name": null, "date": "2026 Jan 9", "date_precision": "day", "issue": "", "normalized_date": "2026-01-09", "pages": "S2666-6367(26)00017-5", "proceedings_title": null, "publisher": "", "title": "Transplantation and cellular therapy", "volume": "", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "Tracking of donor erythropoiesis following ABO-incompatible allogeneic hematopoietic stem cell transplantation.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The JNK pathway converts graded (analogue) stress stimuli into a switch-like (digital) response, thereby dictating binary, all-or-none cell-fate decisions such as survival or death. However, the underlying mechanism remains unclear. Here, we report that the stress-induced modulation of MKK4 spatiotemporal dynamics serves as an analogue-to-digital converter for JNK signalling. Under steady-state conditions, MKK4 shuttles slowly between the nucleus and cytoplasm, but its shuttling rate increases markedly under stress via JNK-mediated feedback regulation. Experimental and mathematical analyses reveal that the increased shuttling rate, coupled with the predominant nuclear localisation of MKK4, cooperatively generates a switch-like JNK activation in response to graded stress stimuli. Disruption of this mechanism provokes graded JNK activity proportional to stress intensity, thereby aberrantly triggering apoptosis, pro-inflammatory cytokine production, and developmental abnormalities, even under mild stress in human cells and zebrafish embryos. Our findings reveal the fundamental molecular mechanism that maintains biological homeostasis under fluctuating environmental conditions.", "classifications": [ { "id": "JPMJCR2022", "label": "JPMJCR2022", "researcher": "Mutsuhiro Takekawa", "type": "grant" }, { "id": "Suzuki", "label": "Group Suzuki", "parent": "Takekawa", "type": "group" }, { "id": "Takekawa", "label": "Group Takekawa", "parent": "Takekawa", "type": "group" }, { "id": "Takekawa", "label": "Team Takekawa", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Hisashi", "last_name": "Moriizumi", "name": null }, { "creator_type": "author", "first_name": "Takanori", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Yuji", "last_name": "Kubota", "name": null }, { "creator_type": "author", "first_name": "Ryosuke", "last_name": "Hiranuma", "name": null }, { "creator_type": "author", "first_name": "Youngmin", "last_name": "Cho", "name": null }, { "creator_type": "author", "first_name": "Toru", "last_name": "Kawanishi", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Takeda", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Mutsuhiro", "last_name": "Takekawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41467-025-67943-7" }, "pmcid": { "normalized": "PMC12783738" }, "pmid": { "normalized": "41507179" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Apoptosis", "descriptor_ui": "D017209", "major_topic": false }, { "descriptor": "Cell Nucleus", "descriptor_ui": "D002467", "major_topic": false }, { "descriptor": "Cytoplasm", "descriptor_ui": "D003593", "major_topic": false }, { "descriptor": "Embryo, Nonmammalian", "descriptor_ui": "D004625", "major_topic": false }, { "descriptor": "Enzyme Activation", "descriptor_ui": "D004789", "major_topic": false }, { "descriptor": "HeLa Cells", "descriptor_ui": "D006367", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "JNK Mitogen-Activated Protein Kinases", "descriptor_ui": "D048031", "major_topic": true }, { "descriptor": "MAP Kinase Kinase 4", "descriptor_ui": "D048670", "major_topic": true }, { "descriptor": "MAP Kinase Signaling System", "descriptor_ui": "D020935", "major_topic": true }, { "descriptor": "Stress, Physiological", "descriptor_ui": "D013312", "major_topic": false }, { "descriptor": "Zebrafish", "descriptor_ui": "D015027", "major_topic": false } ], "publication": { "conference_name": null, "date": "2026 Jan 8", "date_precision": "day", "issue": "1", "normalized_date": "2026-01-08", "pages": "97", "proceedings_title": null, "publisher": "", "title": "Nature communications", "volume": "17", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "Spatiotemporal regulation of MKK4 dictates switch-like JNK activation and binary cell-fate decisions.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Mitochondrial cysteinyl-transfer RNA synthetase 2 (CARS2) is involved not only in the ligation of cysteine to transfer RNA but also in the synthesis of intracellular supersulfides. In this study, we investigated the role of CARS2 in the survival of retinal ganglion cells (RGCs) under excitotoxic conditions. Immunohistochemical analysis showed strong expression of CARS2 in RBPMS-positive RGCs in the mouse retina. Overexpression of exogenous human CARS2 (hCARS2) in mouse retinas and in the rat-derived retinal cell line R28 did not affect endogenous CARS2 mRNA levels. Adeno-associated virus 2-mediated overexpression of hCARS2 in RGCs significantly reduced cell death induced by excitotoxicity following intravitreal injection of N-methyl-D-aspartate. Similarly, hCARS2 overexpression decreased glutamate-induced excitotoxic cell death in R28 cells. Quantitative reverse transcription polymerase chain reaction analysis demonstrated a significant increase in CARS2 expression in R28 cells treated with glutamate. Using specific probes, we found that hCARS2-overexpressing R28 cells treated with glutamate exhibited higher intracellular levels of sulfane sulfur species and lower levels of reactive oxygen species (ROS) than control cells with basal CARS2 expression. Moreover, the oxidative stress marker gene Hmox1 was significantly downregulated in CARS2-overexpressing R28 cells compared with control cells. Taken together, these findings suggest that CARS2 plays a critical role in protecting retinal cells from excitotoxic cell death by increasing sulfane sulfur production and decreasing ROS accumulation. Given that CARS2 is predominantly expressed in RGCs among retinal cells, it may serve as a preemptive defense mechanism that enhances antioxidative activity at basal expression levels to support RGC survival.", "classifications": [ { "id": "Akaike", "label": "Group Akaike", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yuri", "last_name": "Chida", "name": null }, { "creator_type": "author", "first_name": "Risa", "last_name": "Shiokawa", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Tawarayama", "name": null }, { "creator_type": "author", "first_name": "Minami", "last_name": "Takeda", "name": null }, { "creator_type": "author", "first_name": "Hirokazu", "last_name": "Hasegawa", "name": null }, { "creator_type": "author", "first_name": "Naoki", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Kunikata", "name": null }, { "creator_type": "author", "first_name": "Takaaki", "last_name": "Akaike", "name": null }, { "creator_type": "author", "first_name": "Toru", "last_name": "Nakazawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.freeradbiomed.2026.01.009" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "41506554" } }, "mesh": [ { "descriptor": "Amino Acyl-tRNA Synthetases", "descriptor_ui": "D000604", "major_topic": true }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Death", "descriptor_ui": "D016923", "major_topic": false }, { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "Glutamic Acid", "descriptor_ui": "D018698", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mitochondria", "descriptor_ui": "D008928", "major_topic": true }, { "descriptor": "N-Methylaspartate", "descriptor_ui": "D016202", "major_topic": false }, { "descriptor": "Oxidative Stress", "descriptor_ui": "D018384", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Reactive Oxygen Species", "descriptor_ui": "D017382", "major_topic": false }, { "descriptor": "Retina", "descriptor_ui": "D012160", "major_topic": true }, { "descriptor": "Retinal Ganglion Cells", "descriptor_ui": "D012165", "major_topic": true }, { "descriptor": "Sulfides", "descriptor_ui": "D013440", "major_topic": true } ], "publication": { "conference_name": null, "date": "2026 Jan 6", "date_precision": "day", "issue": "", "normalized_date": "2026-01-06", "pages": "S0891-5849(26)00015-8", "proceedings_title": null, "publisher": "", "title": "Free radical biology & medicine", "volume": "", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "Mitochondrial Cysteinyl-tRNA Synthetase 2 Protects Against Excitotoxic Retinal Cell Death via Enhanced Supersulfide Production.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "In multiline-illumination Raman microscopy, background signals from the out-of-focus planes limit the throughput of cell imaging. Here, we improved the throughput of cell imaging by reducing background signals originating from the sample buffer solution and immersion medium of the objective lens. The background from water was suppressed by restricting the thickness of the sample buffer layer. In addition, the background signal in the CH stretching region was suppressed by replacing H(2)O with D(2)O as the immersion medium. These approaches successfully decreased background signals by 75%, enabling the same signal-to-noise ratio with a 2.2-fold shorter exposure time in cell imaging. Finally, we demonstrated high-throughput Raman imaging by visualizing bead uptake in living macrophages, successfully capturing 80 cells per frame within 3 min.", "classifications": [ { "id": "Fujita", "label": "Group Fujita", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Tomoaki", "last_name": "Okumura", "name": null }, { "creator_type": "author", "first_name": "Yasuaki", "last_name": "Kumamoto", "name": null }, { "creator_type": "author", "first_name": "Nicholas Isaac", "last_name": "Smith", "name": null }, { "creator_type": "author", "first_name": "Katsumasa", "last_name": "Fujita", "name": null } ], "identifiers": { "doi": { "normalized": "10.1364/boe.578769" }, "pmcid": { "normalized": "PMC12795448" }, "pmid": { "normalized": "41532118" } }, "mesh": [], "publication": { "conference_name": null, "date": "2026 Jan 1", "date_precision": "day", "issue": "1", "normalized_date": "2026-01-01", "pages": "160-171", "proceedings_title": null, "publisher": "", "title": "Biomedical optics express", "volume": "17", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "High-throughput spontaneous Raman imaging of biological specimens with water background reduction.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: Hepatocellular carcinoma has poor prognosis due to its high recurrence rate, even after curative surgery. Epigenetic regulators are known to play a critical role in cancer progression, and the histone methyltransferase SETD8/KMT5A has been reported to be overexpressed in various malignancies. In this study, we aimed to elucidate the role of SETD8/KMT5A in hepatocellular carcinoma. METHODS: We investigated SETD8/KMT5A expression in 345 primary hepatocellular carcinoma resection specimens through immunohistochemical staining. For functional analyses, we conducted a loss-of-function study of SETD8/KMT5A using hepatocellular carcinoma cell lines, including in vitro assays for proliferation, cell cycle, invasion, and RNA sequencing with gene ontology analysis. Additionally, we performed xenograft experiments in mice and performed similar experiments using the SETD8/KMT5A inhibitor UNC0379. RESULTS: All cases were divided into either the SETD8 high-expression (n = 197) or low-expression (n = 148) groups. The high-expression group exhibited significantly poorer 5-year overall survival and 2- and 5-year disease-free survival compared with the low-expression group (both p < 0.001). Multivariate analysis indicated that high SETD8 expression was an independent poor prognosis factor in overall (p = 0.0255) and disease-free (p = 0.0051) survival. SETD8/KMT5A knockdown suppressed proliferation by inhibition of G1 to S phase transition (p < 0.001). Gene ontology terms were related to cancer progression, including cell adhesion, MAPK-related signaling and chromatin remodeling. SETD8/KMT5A knockout using CRISPR/Cas9 inhibited tumor growth (p < 0.01) in vivo. CONCLUSIONS: SETD8/KMT5A overexpression was associated with poor prognosis and was an independent prognostic factor in hepatocellular carcinoma. In vitro and in vivo analysis, the inhibition of SETD8 could repress hepatocellular carcinoma progression through the regulation of cell activity and cell cycle transition.", "classifications": [ { "id": "Hamamoto", "label": "Group Hamamoto", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Norihiko", "last_name": "Suzaki", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Hayami", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Miyamoto", "name": null }, { "creator_type": "author", "first_name": "Masashi", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Tomohiro", "last_name": "Yoshimura", "name": null }, { "creator_type": "author", "first_name": "Kensuke", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Yoshinobu", "last_name": "Shigekawa", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Shimizu", "name": null }, { "creator_type": "author", "first_name": "Yuji", "last_name": "Kitahata", "name": null }, { "creator_type": "author", "first_name": "Akihiro", "last_name": "Takeuchi", "name": null }, { "creator_type": "author", "first_name": "Hideki", "last_name": "Motobayashi", "name": null }, { "creator_type": "author", "first_name": "Shigehiro", "last_name": "Osada", "name": null }, { "creator_type": "author", "first_name": "Shogo", "last_name": "Ehata", "name": null }, { "creator_type": "author", "first_name": "Ryuji", "last_name": "Hamamoto", "name": null }, { "creator_type": "author", "first_name": "Manabu", "last_name": "Kawai", "name": null } ], "identifiers": { "doi": { "normalized": "10.1371/journal.pone.0337503" }, "pmcid": { "normalized": "PMC13075679" }, "pmid": { "normalized": "41973766" } }, "mesh": [ { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Carcinoma, Hepatocellular", "descriptor_ui": "D006528", "major_topic": true }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Cell Proliferation", "descriptor_ui": "D049109", "major_topic": false }, { "descriptor": "Disease Progression", "descriptor_ui": "D018450", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Gene Expression Regulation, Neoplastic", "descriptor_ui": "D015972", "major_topic": false }, { "descriptor": "Histone-Lysine N-Methyltransferase", "descriptor_ui": "D011495", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Liver Neoplasms", "descriptor_ui": "D008113", "major_topic": true }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Nude", "descriptor_ui": "D008819", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Prognosis", "descriptor_ui": "D011379", "major_topic": false } ], "publication": { "conference_name": null, "date": "2026", "date_precision": "year", "issue": "4", "normalized_date": "2026", "pages": "e0337503", "proceedings_title": null, "publisher": "", "title": "PloS one", "volume": "21", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "Impact of SETD8/KMT5A overexpression on hepatocellular carcinoma progression and prognosis.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Allogeneic hematopoietic stem cell transplantation is the only curative treatment for myelofibrosis. However, the high risk of non-relapse mortality and the difficulty of finding an HLA-matched sibling donor are obstacles, given the advanced age at disease onset. Here, we report four cases of transplantation from an HLA-haploidentical donor using post-transplant cyclophosphamide (PTCy-haplo) in three recipients with primary (n=1) and secondary (n=2) myelofibrosis. The median age was 52 years, and one patient had received JAK2 inhibitor therapy prior to transplantation. The sources were bone marrow and peripheral blood stem cells (two cases each); myeloablative conditioning was used in two cases. Neutrophil engraftment was achieved in all cases (median 19 days); however, prolonged G-CSF administration (median 44 days) was required, and platelet engraftment was delayed (median 68 days). Two patients survived without relapse, with observation periods of 3.5 and 8 years, respectively. One patient relapsed 17 months after the first transplantation and died of pneumonia 49 days after second PTCy-haplo. These findings suggest that PTCy-haplo is a feasible option for patients with myelofibrosis; however, the risk of delayed hematopoietic recovery should be noted.", "classifications": [ { "id": "Nishikii", "label": "Group Nishikii", "parent": "Shintaku", "type": "group" }, { "id": "Shintaku", "label": "Team Shintaku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Toshihiro", "last_name": "Miyakoshi", "name": null }, { "creator_type": "author", "first_name": "Naoki", "last_name": "Kurita", "name": null }, { "creator_type": "author", "first_name": "Kenichi", "last_name": "Makishima", "name": null }, { "creator_type": "author", "first_name": "Sakurako", "last_name": "Suma", "name": null }, { "creator_type": "author", "first_name": "Fumiaki", "last_name": "Matsumura", "name": null }, { "creator_type": "author", "first_name": "Yuya", "last_name": "Sasaki", "name": null }, { "creator_type": "author", "first_name": "Yasuhito", "last_name": "Suehara", "name": null }, { "creator_type": "author", "first_name": "Keiichiro", "last_name": "Hattori", "name": null }, { "creator_type": "author", "first_name": "Tatsuhiro", "last_name": "Sakamoto", "name": null }, { "creator_type": "author", "first_name": "Takayasu", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Hidekazu", "last_name": "Nishikii", "name": null }, { "creator_type": "author", "first_name": "Naoshi", "last_name": "Obara", "name": null }, { "creator_type": "author", "first_name": "Mamiko", "last_name": "Sakata-Yanagimoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.11406/rinketsu.67.310" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "42128860" } }, "mesh": [ { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Cyclophosphamide", "descriptor_ui": "D003520", "major_topic": true }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Hematopoietic Stem Cell Transplantation", "descriptor_ui": "D018380", "major_topic": true }, { "descriptor": "HLA Antigens", "descriptor_ui": "D006680", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Primary Myelofibrosis", "descriptor_ui": "D055728", "major_topic": true }, { "descriptor": "Transplantation Conditioning", "descriptor_ui": "D019172", "major_topic": false }, { "descriptor": "Transplantation, Haploidentical", "descriptor_ui": "D000075442", "major_topic": true } ], "publication": { "conference_name": null, "date": "2026", "date_precision": "year", "issue": "4", "normalized_date": "2026", "pages": "310-315", "proceedings_title": null, "publisher": "", "title": "[Rinsho ketsueki] The Japanese journal of clinical hematology", "volume": "67", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "[HLA-haploidentical hematopoietic stem cell transplantation with post-transplant cyclophosphamide in patients with myelofibrosis].", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Among carnivorous plants, the Venus flytrap (Dionaea muscipula) is known for its rapid (<1 s) trap closure. Although buckling instability, hydrostatic pressure, and hydroelastic coupling have all been proposed to be involved, the nature of this process and the relationship between trap size and curvature remain elusive. Here, we monitored the closure of Venus flytraps and performed micro-CT scanning and 3D reconstruction, revealing that increasing angular velocity was correlated with higher values of a non-dimensional shape index. Based on these experimental data, we constructed a geometric model of the trap that takes leaf orientation into account. We found that leaf curvature is dependent on leaf size, a relationship we denote as a size-curvature constraint. We further propose a curvature design derived from differential deformations of a two-layer model of the leaf, which could be a powerful tool to control the curvatures of soft and bending surface structures in the field of biomimetics.", "classifications": [ { "id": "JPMJCR2121", "label": "JPMJCR2121", "researcher": "Minako Ueda", "type": "grant" }, { "id": "Tsugawa", "label": "Group Tsugawa", "parent": "Ueda", "type": "group" }, { "id": "Ueda", "label": "Group Ueda", "parent": "Ueda", "type": "group" }, { "id": "Ueda", "label": "Team Ueda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Michiko", "last_name": "Hirata", "name": null }, { "creator_type": "author", "first_name": "Zichen", "last_name": "Kang", "name": null }, { "creator_type": "author", "first_name": "Hiroki", "last_name": "Asakawa", "name": null }, { "creator_type": "author", "first_name": "Hiraku", "last_name": "Suda", "name": null }, { "creator_type": "author", "first_name": "Masatsugu", "last_name": "Toyota", "name": null }, { "creator_type": "author", "first_name": "Yuji", "last_name": "Ohashi", "name": null }, { "creator_type": "author", "first_name": "Satoru", "last_name": "Tsugawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1371/journal.pone.0349246" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "42189827" } }, "mesh": [ { "descriptor": "Biomechanical Phenomena", "descriptor_ui": "D001696", "major_topic": false }, { "descriptor": "Droseraceae", "descriptor_ui": "D031257", "major_topic": true }, { "descriptor": "Models, Biological", "descriptor_ui": "D008954", "major_topic": false }, { "descriptor": "Motion", "descriptor_ui": "D009038", "major_topic": false }, { "descriptor": "Movement", "descriptor_ui": "D009068", "major_topic": false }, { "descriptor": "Plant Leaves", "descriptor_ui": "D018515", "major_topic": true }, { "descriptor": "X-Ray Microtomography", "descriptor_ui": "D055114", "major_topic": false } ], "publication": { "conference_name": null, "date": "2026", "date_precision": "year", "issue": "5", "normalized_date": "2026", "pages": "e0349246", "proceedings_title": null, "publisher": "", "title": "PloS one", "volume": "21", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "Size-curvature constraint in the closing motion of Venus flytrap leaves.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by progressive loss of motor neurons. Accurate and accessible blood-based diagnostics for neurodegenerative diseases, including ALS, are being progressively required. Although blood cell gene expression profiles have potential clinical utility for distinguishing ALS, robust transcriptomic biomarkers for supportive diagnosis have not yet been established. Here, we analyzed publicly available peripheral blood mononuclear cell (PBMC) transcriptomic data from ALS patients using Maximum Mean Discrepancy, a kernel-based method that captures nonlinear distributional differences in a reproducing kernel Hilbert space and enables the extraction of informative gene combinations while minimizing multicollinearity, a common issue in multiple regression models. Using this approach, we identified a nonlinear three-gene combination-PRKAR1A, QPCT, and TMEM71-that distinguished ALS from healthy controls with an area under the curve (AUC) of 0.83 in a public PBMC dataset. This achievement was confirmed in laboratory PBMC samples with an AUC of 0.85, supporting the robustness of the identified gene signature in independent samples. Furthermore, these genes also enabled ALS classification in induced pluripotent stem cell-derived motor neurons with an AUC of 0.79. Knockdown of PRKAR1A, QPCT, or TMEM71 in motor neurons increased the TDP-43 expression levels, and PRKAR1A knockdown induced the mislocalization of TDP-43, accompanied by phosphorylation, suggesting a potential link to ALS-related pathophysiology. These findings suggest that nonlinear gene combinations may provide a useful strategy for identifying blood-based biomarkers and offer insights into ALS pathogenesis. This nonlinear, data-driven analytical framework enabled the transition from unbiased gene discovery to the identification of pathophysiology-associated molecules by in vitro functional validation.", "classifications": [ { "id": "Yamamoto", "label": "Group Yamamoto", "parent": "Toyoshima", "type": "group" }, { "id": "Toyoshima", "label": "Team Toyoshima", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Keiko", "last_name": "Imamura", "name": null }, { "creator_type": "author", "first_name": "Ayako", "last_name": "Nagahashi", "name": null }, { "creator_type": "author", "first_name": "Aya", "last_name": "Okusa", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Yuishin", "last_name": "Izumi", "name": null }, { "creator_type": "author", "first_name": "Naonori", "last_name": "Ueda", "name": null }, { "creator_type": "author", "first_name": "Yoshinobu", "last_name": "Kawahara", "name": null }, { "creator_type": "author", "first_name": "Haruhisa", "last_name": "Inoue", "name": null } ], "identifiers": { "doi": { "normalized": "10.1093/biomethods/bpag023" }, "pmcid": { "normalized": "PMC13293084" }, "pmid": { "normalized": "42359392" } }, "mesh": [], "publication": { "conference_name": null, "date": "2026", "date_precision": "year", "issue": "1", "normalized_date": "2026", "pages": "bpag023", "proceedings_title": null, "publisher": "", "title": "Biology methods & protocols", "volume": "11", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "Nonlinear combinatorial analysis of blood transcriptomes identifies PRKAR1A as a regulator of TDP-43 pathophysiology in amyotrophic lateral sclerosis.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Although tumor-associated autoantibodies (TAAbs) are promising biomarkers for early cancer detection, the diagnostic performance of individual TAAbs for esophageal squamous cell carcinoma (ESCC) remains limited. In this study, we constructed machine learning (ML) models for ESCC diagnosis using the serum levels of 6 TAAbs (c-myc, NY-ESO-1, p53, p62, RalA, and Sui1) and compared their performance with that of a conventional approach. When the training and test datasets were combined, serum samples from 339 patients with ESCC and 152 healthy controls were analyzed. To address class imbalance, the training data were oversampled using the synthetic minority oversampling technique. Classification models were developed using 5 ML algorithms, among which the svmLinear (support vector machine with a linear kernel), svmRadial (support vector machines with a radial basis function kernel), and neural network models demonstrated robust performance without overfitting. At specificities exceeding 90%, these models achieved substantially higher sensitivities than those obtained using any single TAAb. Notably, the svmLinear and neural network models achieved sensitivities greater than 40% for early-stage ESCC (stage 0/I) in the test dataset. Overall, the integration of multiple TAAbs with ML substantially improved the diagnostic performance for ESCC, highlighting the clinical potential of ML-based approaches.", "classifications": [ { "id": "Suzuki", "label": "Group Suzuki", "parent": "Takekawa", "type": "group" }, { "id": "Takekawa", "label": "Team Takekawa", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yosui", "last_name": "Nojima", "name": null }, { "creator_type": "author", "first_name": "Fumiaki", "last_name": "Shiratori", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Yajima", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Toyozumi", "name": null }, { "creator_type": "author", "first_name": "Hideaki", "last_name": "Shimada", "name": null } ], "identifiers": { "doi": { "normalized": "10.34133/csbj.0025" }, "pmcid": { "normalized": "PMC13068007" }, "pmid": { "normalized": "41971943" } }, "mesh": [], "publication": { "conference_name": null, "date": "2026", "date_precision": "year", "issue": "1", "normalized_date": "2026", "pages": "0025", "proceedings_title": null, "publisher": "", "title": "Computational and structural biotechnology journal", "volume": "35", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "Computational Approach Improves Diagnostic Performance Based on Tumor-Associated Autoantibodies in Esophageal Squamous Cell Carcinoma.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Self-renewing divisions of stem cells at the growing tip universally govern plant development. In basal land plants, a single apical stem cell (AC) undergoes successive 120-degree rotational divisions while maintaining a self-similar tetrahedral geometry with three division walls, recapitulating the helically symmetric body architecture. The mechanisms by which AC geometry and mechanics determine the division axis and its rotation are largely unknown. Here, we develop two 3D multicellular mathematical models to address these questions. Our geometrical model reveals that the least area rule, coordinated with the AC surface curvature, is sufficient to drive rotational divisions by rotating the geometric proportion of the AC. Furthermore, by incorporating biologically plausible cell growth mechanics, we show that the tetrahedral AC and its rotational division spontaneously emerge from a spherical cell. Notably, the maximal tension rule confers superior robustness against stochastic fluctuations in division orientation compared to the least area rule, because the sequential formation of division walls continuously updates the tension distribution to guide subsequent orientation. These results suggest that the tetrahedral AC and the helically symmetric body plan are natural consequences of self-renewing cell divisions, imposed by 3D geometry and/or mechanics.", "classifications": [ { "id": "JPMJCR2121", "label": "JPMJCR2121", "researcher": "Minako Ueda", "type": "grant" }, { "id": "Ueda", "label": "Group Ueda", "parent": "Ueda", "type": "group" }, { "id": "Ueda", "label": "Team Ueda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Naoya", "last_name": "Kamamoto", "name": null }, { "creator_type": "author", "first_name": "Koichi", "last_name": "Fujimoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.3389/fpls.2026.1852286" }, "pmcid": { "normalized": "PMC13422487" }, "pmid": { "normalized": "42535113" } }, "mesh": [], "publication": { "conference_name": null, "date": "2026", "date_precision": "year", "issue": "", "normalized_date": "2026", "pages": "1852286", "proceedings_title": null, "publisher": "", "title": "Frontiers in plant science", "volume": "17", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "3D geometry and mechanics of a single apical stem cell ensure helically symmetric plant body in multicellular models.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Lentivirus vectors are capable of efficient gene transfer to nondividing cells, in addition to dividing cells. Therefore, lentivirus vectors can also be used for gene transfer into dormant stem cells in the postnatal and adult brains of experimental animals, many of which have ceased cell division. For example, it is known that neural stem cells (NSCs) are present around the lateral ventricle and in the dentate gyrus of the hippocampus in the postnatal and adult brain and continue to give rise to neurons. However, the majority of these NSCs are considered to be quiescent, and lentivirus vectors are an important tool to enable gene transfer to dormant stem cells. Lentivirus vectors are also capable of multiple infection of the same cells, making them an important option for experiments requiring high gene expression levels. By selecting transduced cells after infection with high titer lentivirus vectors and repeating infection, genes that are difficult to express or gene sequences that require high copy number can be introduced into cells with high efficiency. In this chapter, we present examples of gene transfer to NSCs localized at the hippocampal dentate gyrus in mice using lentivirus vectors and establishment of stable transgenic NSC lines by multiple infections.", "classifications": [ { "id": "Imayoshi", "label": "Group Imayoshi", "parent": "Imayoshi", "type": "group" }, { "id": "Imayoshi", "label": "Team Imayoshi", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Itaru", "last_name": "Imayoshi", "name": null }, { "creator_type": "author", "first_name": "Mayumi", "last_name": "Yamada", "name": null }, { "creator_type": "author", "first_name": "Shinji C.", "last_name": "Nagasaki", "name": null }, { "creator_type": "author", "first_name": "Tomonori D.", "last_name": "Fukuda", "name": null }, { "creator_type": "author", "first_name": "Ikumi", "last_name": "Nagano", "name": null }, { "creator_type": "author", "first_name": "Tomohisa", "last_name": "Toda", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/978-1-0716-4807-0_12" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "41273647" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Dentate Gyrus", "descriptor_ui": "D018891", "major_topic": false }, { "descriptor": "Gene Transfer Techniques", "descriptor_ui": "D018014", "major_topic": false }, { "descriptor": "Genetic Vectors", "descriptor_ui": "D005822", "major_topic": true }, { "descriptor": "Lentivirus", "descriptor_ui": "D016086", "major_topic": true }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Neural Stem Cells", "descriptor_ui": "D058953", "major_topic": true }, { "descriptor": "Neurogenesis", "descriptor_ui": "D055495", "major_topic": true }, { "descriptor": "Transduction, Genetic", "descriptor_ui": "D014161", "major_topic": false } ], "publication": { "conference_name": null, "date": "2026", "date_precision": "year", "issue": "", "normalized_date": "2026", "pages": "141-151", "proceedings_title": null, "publisher": "", "title": "Methods in molecular biology (Clifton, N.J.)", "volume": "2974", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "Application of Lentivirus Vectors to Adult Neurogenesis and Manipulation of Neural Stem Cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Cardioembolic stroke caused by tumor emboli is a rare form of cancer-associated stroke. We report a case of a patient with cardiac metastasis of extraskeletal chondrosarcoma who developed left internal carotid artery occlusion due to embolic stroke. Extraskeletal chondrosarcoma is an extremely rare subtype of soft tissue sarcoma characterized by a tendency for local recurrence and metastasis. Endovascular thrombectomy was performed using a combined technique, achieving complete revascularization. Histopathological analysis of the retrieved cell mass confirmed that the embolic source was the preexisting extraskeletal chondrosarcoma.", "classifications": [ { "id": "Fujimoto", "label": "Group Fujimoto", "parent": "Ueda", "type": "group" }, { "id": "Ueda", "label": "Team Ueda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yasuhiro", "last_name": "Kawabata", "name": null }, { "creator_type": "author", "first_name": "Osamu", "last_name": "Kawakami", "name": null }, { "creator_type": "author", "first_name": "Kimihiko", "last_name": "Tamura", "name": null }, { "creator_type": "author", "first_name": "Koichi", "last_name": "Fujimoto", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Tamura", "name": null }, { "creator_type": "author", "first_name": "Motohiro", "last_name": "Kajiwara", "name": null }, { "creator_type": "author", "first_name": "Tomoya", "last_name": "Myojin", "name": null }, { "creator_type": "author", "first_name": "Emi", "last_name": "Date", "name": null }, { "creator_type": "author", "first_name": "Norishige", "last_name": "Iizuka", "name": null }, { "creator_type": "author", "first_name": "Ayumi", "last_name": "Iwamuro", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Kawashima", "name": null } ], "identifiers": { "doi": { "normalized": "10.2176/jns-nmc.2025-0216" }, "pmcid": { "normalized": "PMC12962739" }, "pmid": { "normalized": "41799218" } }, "mesh": [], "publication": { "conference_name": null, "date": "2026", "date_precision": "year", "issue": "", "normalized_date": "2026", "pages": "27-32", "proceedings_title": null, "publisher": "", "title": "NMC case report journal", "volume": "13", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "Endovascular Thrombectomy in a Patient with Acute Ischemic Stroke due to Tumor Emboli Associated with Cardiac Metastasis of Extraskeletal Myxoid Chondrosarcoma: A Case Report.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: C-type lectin-like domain family 2 (CLEC2D), a transmembrane protein, is a ligand for the inhibitory receptor CD161, which is expressed in several types of immune cells. CLEC2D expressed on cancer cells suppresses antitumor effect of these cells by interacting with CD161 in human malignancies. However, its clinical significance in breast cancer and its direct biological role in cancer cells remain largely unclear. METHODS: In this study, we immunolocalized CLEC2D in 174 breast cancer tissues and correlated its immunoreactivity with clinicopathological parameters and clinical outcomes. Additionally, we conducted in vitro assays to examine the effects of CLEC2D on the proliferation and migration of breast cancer cell lines. RESULTS: CLEC2D immunoreactivity was predominantly detected in the cytoplasm of breast cancer cells and was associated with increased proliferation and invasion, as well as poor clinical outcomes especially in those who had received chemotherapy. In vitro experiments demonstrated that the knockdown of CLEC2D significantly suppressed the proliferation and migration of MCF-7, MDA-MB-231, T-47D breast cancer cells. CONCLUSION: We therefore concluded that CLED2D directly promoted breast cancer cell proliferation and migration independently of immune cells and served as a poor prognostic factor in breast cancer.", "classifications": [ { "id": "Suzuki", "label": "Group Suzuki", "parent": "Takekawa", "type": "group" }, { "id": "Takekawa", "label": "Team Takekawa", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Mio", "last_name": "Yamaguchi-Tanaka", "name": null }, { "creator_type": "author", "first_name": "Yui", "last_name": "Kurihara", "name": null }, { "creator_type": "author", "first_name": "Kiyoshi", "last_name": "Takagi", "name": null }, { "creator_type": "author", "first_name": "Ai", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Iori", "last_name": "Yasuda", "name": null }, { "creator_type": "author", "first_name": "Yuto", "last_name": "Yamazaki", "name": null }, { "creator_type": "author", "first_name": "Minoru", "last_name": "Miyashita", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Suzuki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/s12282-025-01777-5" }, "pmcid": { "normalized": "PMC12789214" }, "pmid": { "normalized": "40938562" } }, "mesh": [ { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Biomarkers, Tumor", "descriptor_ui": "D014408", "major_topic": true }, { "descriptor": "Breast Neoplasms", "descriptor_ui": "D001943", "major_topic": true }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Cell Movement", "descriptor_ui": "D002465", "major_topic": false }, { "descriptor": "Cell Proliferation", "descriptor_ui": "D049109", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Lectins, C-Type", "descriptor_ui": "D037181", "major_topic": true }, { "descriptor": "MCF-7 Cells", "descriptor_ui": "D061986", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Neoplasm Invasiveness", "descriptor_ui": "D009361", "major_topic": false }, { "descriptor": "Prognosis", "descriptor_ui": "D011379", "major_topic": false }, { "descriptor": "Receptors, Cell Surface", "descriptor_ui": "D011956", "major_topic": false }, { "descriptor": "Receptors, Mitogen", "descriptor_ui": "D011975", "major_topic": true } ], "publication": { "conference_name": null, "date": "2026 Jan", "date_precision": "unknown", "issue": "1", "normalized_date": null, "pages": "88-98", "proceedings_title": null, "publisher": "", "title": "Breast cancer (Tokyo, Japan)", "volume": "33", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "C-type lectin-like domain family 2 (CLEC2D) promotes proliferation and migration of breast cancer and serves as a poor prognostic factor.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The receptor tyrosine kinase RET regulates the development of multiple neuronal populations through GFRalpha co-receptors and their cognate ligands. Recent work has shown that RET is also required for enteroendocrine cell (EEC) function; however, the specific GFRalpha receptor operating in EECs has remained unclear. Here, we identify GFRalpha3 as the predominant GFRalpha receptor expressed in EECs. To determine its cell-autonomous role, we generated a Gfralpha3 conditional allele and inactivated the Gfralpha3 gene specifically in the intestinal epithelium. These Gfralpha3 IEcKO mice exhibited a selective reduction in the number of CCK(+) EECs among multiple EEC subtypes. A comparative decrease in CCK(+) EECs in Ret IEcKO mice suggests that RET/GFRalpha3 signaling is required for the development and/or maintenance of this EEC lineage. Although CCK(+) EECs can indirectly influence glucose metabolism, Gfralpha3 IEcKO mice showed no significant change in glucose tolerance under high-fat diet (HFD) conditions. In contrast, they exhibited modest lipid malabsorption on HFD. Together, these findings demonstrate that GFRalpha3 is implicated in the structure and function of CCK EECs and highlight the utility of the Gfralpha3 conditional allele for dissecting the biology of GFRalpha3-expressing cells.", "classifications": [ { "id": "JPMJCR2021", "label": "JPMJCR2021", "researcher": "Hideki Enomoto", "type": "grant" }, { "id": "Enomoto", "label": "Group Enomoto", "parent": "Enomoto", "type": "group" }, { "id": "Enomoto", "label": "Team Enomoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Susan", "last_name": "Simanjaya", "name": null }, { "creator_type": "author", "first_name": "Masato", "last_name": "Kinoshita", "name": null }, { "creator_type": "author", "first_name": "Mukhamad", "last_name": "Sunardi", "name": null }, { "creator_type": "author", "first_name": "Keisuke", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Masakazu", "last_name": "Shinohara", "name": null }, { "creator_type": "author", "first_name": "Takaya", "last_name": "Abe", "name": null }, { "creator_type": "author", "first_name": "Yuzo", "last_name": "Kodama", "name": null }, { "creator_type": "author", "first_name": "Toshihiro", "last_name": "Uesaka", "name": null }, { "creator_type": "author", "first_name": "Hideki", "last_name": "Enomoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/dvg.70043" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "41699909" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cholecystokinin", "descriptor_ui": "D002766", "major_topic": true }, { "descriptor": "Enteroendocrine Cells", "descriptor_ui": "D019858", "major_topic": true }, { "descriptor": "Glial Cell Line-Derived Neurotrophic Factor Receptors", "descriptor_ui": "D051097", "major_topic": true }, { "descriptor": "Intestinal Mucosa", "descriptor_ui": "D007413", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Proto-Oncogene Proteins c-ret", "descriptor_ui": "D051096", "major_topic": true }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false } ], "publication": { "conference_name": null, "date": "2026 Feb", "date_precision": "unknown", "issue": "1", "normalized_date": null, "pages": "e70043", "proceedings_title": null, "publisher": "", "title": "Genesis (New York, N.Y. : 2000)", "volume": "64", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "A Gfralpha3 Conditional Knockout Mouse Reveals a Requirement for GFRalpha3/RET Signaling in Cholecystokinin-Positive Enteroendocrine Cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "During epidemics, individuals may adjust their social behavior in response to the threat. This may affect the course of the epidemic, and, in turn, again modify people's behavior. Game theoretically, the system may end up in a Nash equilibrium, where no member of the population can benefit by unilaterally changing their behavior. Compartmentalized epidemic models can incorporate such endogenous decision making, where individuals try to optimize a utility function via their behavior. Typically, such models can only be solved numerically. Here, we extend a recently discovered analytic solution for time-dependent social distancing and the corresponding epidemic dynamics: now, the probability of an infection taking place can depend on both the susceptible and infectious individual behaviors. We show that the more effectively the susceptible individual can reduce the probability of infection, the more self-organized social distancing is expected to occur. The previously identified heuristic that the strength of rational social distancing is proportional to both the perceived infection cost and prevalence is found to also hold in the generalized model.", "classifications": [ { "id": "Kobayashi", "label": "Group Kobayashi", "parent": "Wakamoto", "type": "group" }, { "id": "Wakamoto", "label": "Team Wakamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Simon K.", "last_name": "Schnyder", "name": null }, { "creator_type": "author", "first_name": "John J.", "last_name": "Molina", "name": null }, { "creator_type": "author", "first_name": "Joel C.", "last_name": "Miller", "name": null }, { "creator_type": "author", "first_name": "Ryoichi", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Tetsuya J.", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Matthew S.", "last_name": "Turner", "name": null } ], "identifiers": { "doi": { "normalized": "10.3934/mbe.2026007" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "41494852" } }, "mesh": [ { "descriptor": "Communicable Diseases", "descriptor_ui": "D003141", "major_topic": true }, { "descriptor": "Computer Simulation", "descriptor_ui": "D003198", "major_topic": false }, { "descriptor": "COVID-19", "descriptor_ui": "D000086382", "major_topic": false }, { "descriptor": "Decision Making", "descriptor_ui": "D003657", "major_topic": false }, { "descriptor": "Disease Susceptibility", "descriptor_ui": "D004198", "major_topic": false }, { "descriptor": "Epidemics", "descriptor_ui": "D058872", "major_topic": true }, { "descriptor": "Game Theory", "descriptor_ui": "D005716", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Models, Biological", "descriptor_ui": "D008954", "major_topic": false }, { "descriptor": "Physical Distancing", "descriptor_ui": "D000085762", "major_topic": true }, { "descriptor": "Probability", "descriptor_ui": "D011336", "major_topic": false }, { "descriptor": "Social Behavior", "descriptor_ui": "D012919", "major_topic": true } ], "publication": { "conference_name": null, "date": "2026 Jan", "date_precision": "unknown", "issue": "1", "normalized_date": null, "pages": "148-171", "proceedings_title": null, "publisher": "", "title": "Mathematical biosciences and engineering : MBE", "volume": "23", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "Self-organized social distancing during epidemics when the force of infection depends on susceptible and infectious behavior.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The majority of intestinal tumors harbor mutations in canonical Wnt pathway genes such as APC, whereas the lack of such alterations in a subset of tumors implies alternative tumorigenic routes. Here we identify recurrent in-frame deletion in COPA, frequently co-occurring with USP9X-truncating mutation, in small intestinal adenoma and adenocarcinoma. Patient-derived and CRISPR-engineered small intestinal organoids carrying COPA in-frame deletions exhibit R-spondin-independent yet Wnt ligand-dependent growth, maintaining LGR5 expression without canonical Wnt drivers. Mechanistically, COPA mutation stabilizes the Frizzled coreceptor LRP6 irrespective of R-spondin, sustaining Wnt pathway activation under growth factor-restricted conditions. USP9X loss further potentiates this phenotype. Unlike canonical Wnt pathway members, COPA encodes the alpha-subunit of coatomer complex I, which engages in vesicle trafficking with little prior linkage to intestinal tumorigenesis. Our findings establish COPA mutation as a unique and atypical intestinal tumor driver and implicate USP9X loss as a cooperating lesion.", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Masayuki", "last_name": "Fujii", "name": null }, { "creator_type": "author", "first_name": "Naoko", "last_name": "Abeto", "name": null }, { "creator_type": "author", "first_name": "Shotaro", "last_name": "Kishimoto", "name": null }, { "creator_type": "author", "first_name": "Kouya", "last_name": "Shiraishi", "name": null }, { "creator_type": "author", "first_name": "Taiki", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Nobuyoshi", "last_name": "Hiraoka", "name": null }, { "creator_type": "author", "first_name": "Satoru", "last_name": "Nonaka", "name": null }, { "creator_type": "author", "first_name": "Motohiro", "last_name": "Kojima", "name": null }, { "creator_type": "author", "first_name": "Mami", "last_name": "Matano", "name": null }, { "creator_type": "author", "first_name": "Sirirat", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Gabriele", "last_name": "Colozza", "name": null }, { "creator_type": "author", "first_name": "Bon-Kyoung", "last_name": "Koo", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null }, { "creator_type": "author", "first_name": "Motohiko", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Toshiro", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Shigeki", "last_name": "Sekine", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41588-026-02616-9" }, "pmcid": { "normalized": "PMC13263151" }, "pmid": { "normalized": "42286202" } }, "mesh": [ { "descriptor": "Adenocarcinoma", "descriptor_ui": "D000230", "major_topic": false }, { "descriptor": "Adenoma", "descriptor_ui": "D000236", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Intestinal Neoplasms", "descriptor_ui": "D007414", "major_topic": true }, { "descriptor": "Low Density Lipoprotein Receptor-Related Protein-6", "descriptor_ui": "D060488", "major_topic": false }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": true }, { "descriptor": "R-Spondins", "descriptor_ui": "D000098907", "major_topic": true }, { "descriptor": "Receptors, G-Protein-Coupled", "descriptor_ui": "D043562", "major_topic": false }, { "descriptor": "Ubiquitin Thiolesterase", "descriptor_ui": "D043222", "major_topic": false }, { "descriptor": "Wnt Signaling Pathway", "descriptor_ui": "D060449", "major_topic": true } ], "publication": { "conference_name": null, "date": "2026 Jun", "date_precision": "unknown", "issue": "6", "normalized_date": null, "pages": "1341-1352", "proceedings_title": null, "publisher": "", "title": "Nature genetics", "volume": "58", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "Recurrent COPA mutation drives R-spondin-independent Wnt activation in intestinal tumors.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "One of the most fundamental tasks for a cell to fulfill its function is to move the nucleus to its proper place through a process known as \"nuclear migration.\" In plant cells, the nucleus relocates spontaneously in response to developmental and environmental cues. Root hairs are tip-growing projections of root epidermal cells that are required for the acquisition of water and nutrients from the soil. Before its development, the nucleus travels ∼50 µm across the cell body from the cell center toward the root hair initiation site to support continuous tip growth; however, the dynamics and molecular basis underlying this nuclear migration remain unclear. In this study, we show that long-distance nuclear migration to the root hair initiation site consists of two steps, each driven by distinct F-actin networks. Our cytological and genetic data indicate that the nucleus initially moves downward with the aid of F-actin, which consists of two classes of actin isoforms, ACTIN 7 (ACT7) and ACT2/ACT8, followed by the lateral movement to the root hair initiation site, which is guided by F-actin primarily, incorporating ACT2/ACT8. Moreover, RHO-OF-PLANTS small GTPases play an important role in the formation of F-actin, which connects the nucleus to the root hair initiation site, thus facilitating lateral nuclear movement. This study provides an example of distinct F-actin networks steering the nucleus in a stepwise manner to enable long-distance and precise nuclear migration within plant cells.", "classifications": [ { "id": "JPMJCR2121", "label": "JPMJCR2121", "researcher": "Minako Ueda", "type": "grant" }, { "id": "Higaki", "label": "Group Higaki", "parent": "Ueda", "type": "group" }, { "id": "Ueda", "label": "Group Ueda", "parent": "Ueda", "type": "group" }, { "id": "Ueda", "label": "Team Ueda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Hirotomo", "last_name": "Takatsuka", "name": null }, { "creator_type": "author", "first_name": "Toshiki", "last_name": "Amari", "name": null }, { "creator_type": "author", "first_name": "Takumi", "last_name": "Higaki", "name": null }, { "creator_type": "author", "first_name": "Yoshihisa", "last_name": "Oda", "name": null } ], "identifiers": { "doi": { "normalized": "10.1093/pnasnexus/pgag141" }, "pmcid": { "normalized": "PMC13152013" }, "pmid": { "normalized": "42110321" } }, "mesh": [], "publication": { "conference_name": null, "date": "2026 May", "date_precision": "unknown", "issue": "5", "normalized_date": null, "pages": "pgag141", "proceedings_title": null, "publisher": "", "title": "PNAS nexus", "volume": "5", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "Two-step, long-distance nuclear migration guided by distinct actin networks prior to plant root hair formation.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Thymic T cell development shows homeostasis against various stressors. Invariant natural killer T (iNKT) cells in the thymus contribute to recovery of thymic development after irradiation owing to their initial tolerance to irradiation compared to conventional thymocytes. However, whether and how iNKT cell development recovers from irradiation remains unknown. Here we show that iNKT cells in the thymus exhibit much slower postirradiation recovery than conventional thymocytes. We observed that fluctuation of V and J genes usage does not correlate with the decrease of iNKT cell population and that irradiation markedly elevated the frequency of cell death relative to proliferation in iNKT cells. Mathematical modeling of recovery dynamics of iNKT cell progenitors implied that lack of rapid proliferation immediately after irradiation, unlike conventional thymocytes, contributes to the prolonged reduction of iNKT cell population. These findings indicate that the development of iNKT cells is subject to long-term effects of irradiation which leads to an increased rate of cell death and raise the possibility of an association between the prolonged reduction of iNKT cells after irradiation and autoimmune diseases caused by irradiation in bone marrow transplantation.", "classifications": [ { "id": "Kobayashi", "label": "Group Kobayashi", "parent": "Wakamoto", "type": "group" }, { "id": "Wakamoto", "label": "Team Wakamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Kazumasa B.", "last_name": "Kaneko", "name": null }, { "creator_type": "author", "first_name": "Mio", "last_name": "Hayama", "name": null }, { "creator_type": "author", "first_name": "Nanako", "last_name": "Uchida", "name": null }, { "creator_type": "author", "first_name": "Takahisa", "last_name": "Miyao", "name": null }, { "creator_type": "author", "first_name": "Nobuko", "last_name": "Akiyama", "name": null }, { "creator_type": "author", "first_name": "Taishin", "last_name": "Akiyama", "name": null }, { "creator_type": "author", "first_name": "Tetsuya J.", "last_name": "Kobayashi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/gtc.70077" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "41424361" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Cell Proliferation", "descriptor_ui": "D049109", "major_topic": false }, { "descriptor": "Homeostasis", "descriptor_ui": "D006706", "major_topic": true }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Natural Killer T-Cells", "descriptor_ui": "D055611", "major_topic": true }, { "descriptor": "Receptors, Antigen, T-Cell", "descriptor_ui": "D011948", "major_topic": true }, { "descriptor": "Thymocytes", "descriptor_ui": "D060168", "major_topic": false }, { "descriptor": "Thymus Gland", "descriptor_ui": "D013950", "major_topic": true } ], "publication": { "conference_name": null, "date": "2026 Jan", "date_precision": "unknown", "issue": "1", "normalized_date": null, "pages": "e70077", "proceedings_title": null, "publisher": "", "title": "Genes to cells : devoted to molecular & cellular mechanisms", "volume": "31", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "TCR Repertoire Analysis Quantifies Effect of Irradiation on Homeostasis of iNKT Cell Development in the Thymus of Mice.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Human noroviruses are a leading cause of acute gastroenteritis worldwide, yet the molecular principles governing antibody recognition of their highly repetitive capsid remain poorly understood. Here, we immunized mice with virus-like particles (VLPs) from the pandemic GII.4 strain and the emergent GII.17 strain, generating monoclonal IgM and IgG antibodies via hybridoma technology. High-speed atomic force microscopy visualized IgM antibodies scanning and engaging multiple protruding (P) domains on intact VLPs. Surface plasmon resonance (SPR) analyses of engineered antibodies with identical Fab sequences but different valencies revealed that, unlike monovalent IgG, multivalent IgM exhibits dramatic affinity gains-up to 100-fold-as antigen density increases. This avidity-driven enhancement arises from the dense, repetitive P-domain architecture of the norovirus capsid, enabling IgM to achieve high functional affinity despite modest intrinsic Fab binding. Our findings define how antibody valency and epitope organization cooperate to boost viral recognition, offering a mechanistic framework for designing next-generation vaccines and antiviral antibodies that harness multivalent engagement.", "classifications": [ { "id": "Nishida", "label": "Group Nishida", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Jumpei", "last_name": "Tagawa", "name": null }, { "creator_type": "author", "first_name": "Saeko", "last_name": "Yanaka", "name": null }, { "creator_type": "author", "first_name": "Yuri", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Akitsu", "last_name": "Masuda", "name": null }, { "creator_type": "author", "first_name": "Jae Man", "last_name": "Lee", "name": null }, { "creator_type": "author", "first_name": "Akinobu", "last_name": "Senoo", "name": null }, { "creator_type": "author", "first_name": "Kosuke", "last_name": "Oyama", "name": null }, { "creator_type": "author", "first_name": "Takayuki", "last_name": "Uchihashi", "name": null }, { "creator_type": "author", "first_name": "Motohiro", "last_name": "Nishida", "name": null }, { "creator_type": "author", "first_name": "Takahiro", "last_name": "Kusakabe", "name": null }, { "creator_type": "author", "first_name": "Jose M. M.", "last_name": "Caaveiro", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/pro.70522" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "41820808" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Antibodies, Monoclonal", "descriptor_ui": "D000911", "major_topic": true }, { "descriptor": "Antibodies, Viral", "descriptor_ui": "D000914", "major_topic": true }, { "descriptor": "Antibody Affinity", "descriptor_ui": "D000915", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Immunoglobulin G", "descriptor_ui": "D007074", "major_topic": true }, { "descriptor": "Immunoglobulin M", "descriptor_ui": "D007075", "major_topic": true }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Norovirus", "descriptor_ui": "D029322", "major_topic": true } ], "publication": { "conference_name": null, "date": "2026 Apr", "date_precision": "unknown", "issue": "4", "normalized_date": null, "pages": "e70522", "proceedings_title": null, "publisher": "", "title": "Protein science : a publication of the Protein Society", "volume": "35", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "Characterization of high affinity IgM and IgG monoclonal antibodies against norovirus variants GII.4 and GII.17.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Epigenetic regulation has fundamental roles in the maintenance and differentiation of neural stem cells as well as fate determination of neural lineage. Although neural differentiation is irreversible under physiological conditions, neural dedifferentiation into NSCs was observed under a damaged condition and in an aged brain. However, molecular mechanisms triggering neural fate regulation still remain to be elucidated. In this study, we show that a neural turnover in the adult brain is induced by the lack of JMJD3 using NSC-visualized neural JMJD3 deleted mice. In the JMJD3 deleted brain, a marked expansion of the Nestin-GFP positive population in the hippocampus was observed. Moreover, neurosphere assays revealed not only that JMJD3 deleted neurospheres showed a significantly higher self-renewal potential but also that Nestin-negative neural progenitors converted into a Nestin-positive state in the absence of JMJD3. Intriguingly, a combination of upregulation of Plagl2 and inhibition of Dylk1a as well as increased expressions of HMGAs were detected in the neurospheres lacking JMJD3, suggesting that the lack of JMJD3 could enhance rejuvenation of chromatin state. These results suggest that JMJD3 could be involved in the fate regulation of NSC/NPCs and could provide novel and important insights to promote neural repair and regeneration.", "classifications": [ { "id": "Imayoshi", "label": "Group Imayoshi", "parent": "Imayoshi", "type": "group" }, { "id": "Imayoshi", "label": "Team Imayoshi", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Jiazi", "last_name": "Chen", "name": null }, { "creator_type": "author", "first_name": "Tokuko", "last_name": "Iwamori", "name": null }, { "creator_type": "author", "first_name": "Sakurako", "last_name": "Shima", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Yamaguchi", "name": null }, { "creator_type": "author", "first_name": "Itaru", "last_name": "Imayoshi", "name": null }, { "creator_type": "author", "first_name": "Kinichi", "last_name": "Nakashima", "name": null }, { "creator_type": "author", "first_name": "Naoki", "last_name": "Iwamori", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/gtc.70087" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "41615258" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Jumonji Domain-Containing Histone Demethylases", "descriptor_ui": "D056484", "major_topic": true }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Nestin", "descriptor_ui": "D064231", "major_topic": true }, { "descriptor": "Neural Stem Cells", "descriptor_ui": "D058953", "major_topic": true }, { "descriptor": "Neurogenesis", "descriptor_ui": "D055495", "major_topic": false } ], "publication": { "conference_name": null, "date": "2026 Mar", "date_precision": "unknown", "issue": "2", "normalized_date": null, "pages": "e70087", "proceedings_title": null, "publisher": "", "title": "Genes to cells : devoted to molecular & cellular mechanisms", "volume": "31", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "Turnover of NESTIN-Negative Neural Progenitors Into NESTIN-Positive State by the Lack of JMJD3.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "PURPOSE: Rare cancers are molecularly heterogeneous and lack robust clinical evidence to guide treatment. Whether cancer driver gene expression is governed by tumor lineage or specific somatic alterations-and whether this distinction carries clinical relevance-remains poorly characterized, particularly in Asian populations. This study aimed to determine the relative contributions of tumor lineage and DNA mutations to RNA expression of cancer driver genes and to evaluate the clinical implications of genomic alteration status in Asian patients with rare cancers. METHODS: DNA and RNA were extracted from formalin-fixed paraffin-embedded tumor samples obtained through the MASTER KEY Asia research network. Next-generation sequencing was performed to evaluate genomic alterations and gene expression profiles. RNA expression of cancer driver genes was quantified as TPM Z scores. Elastic net regression with 10-fold cross-validation assessed the relative contributions of tumor lineage and DNA mutations to RNA expression, and findings were independently replicated in another cohort. RESULTS: Integrated DNA and RNA data were available for 128 patients. Tumor lineage was the predominant determinant of RNA expression in 17 of 27 cancer driver genes (63%), whereas ERBB2 and MDM2 demonstrated genomic-predominant regulation, replicated across both cohorts. Alterations in ERBB2 or ARID1A were associated with a lower frequency of disease progression compared with patients without either alteration (P = .01), independently of ERBB2 RNA expression. Functional subclassification of TP53 revealed that gain-of-function mutations were associated with higher rates of disease progression (P = .007) and shorter progression-free survival than loss-of-function variants (hazard ratio, 2.355 [95% CI, 1.086 to 5.105]; P = .029). Tumor mutational burden was not associated with treatment response. CONCLUSION: These findings demonstrate that genomic alteration status, including TP53 functional subclassification, provides clinically meaningful information beyond transcriptional profiling alone, supporting integrative genomics and transcriptomics analysis for precision oncology in rare cancers.", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Kathleen Yasmin", "last_name": "de Almeida", "name": null }, { "creator_type": "author", "first_name": "Marcelo Severino B.", "last_name": "Imasa", "name": null }, { "creator_type": "author", "first_name": "Pei Jye", "last_name": "Voon", "name": null }, { "creator_type": "author", "first_name": "Hwoei Fen", "last_name": "Soo Hoo", "name": null }, { "creator_type": "author", "first_name": "Tom Wei-Wu", "last_name": "Chen", "name": null }, { "creator_type": "author", "first_name": "Suhana", "last_name": "Yusak", "name": null }, { "creator_type": "author", "first_name": "Rangasamy", "last_name": "Ramachandran", "name": null }, { "creator_type": "author", "first_name": "Najihah", "last_name": "Abu Bakar", "name": null }, { "creator_type": "author", "first_name": "Ming-Huang", "last_name": "Chen", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null }, { "creator_type": "author", "first_name": "Kenichi", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Hitomi Sumiyoshi", "last_name": "Okuma", "name": null }, { "creator_type": "author", "first_name": "Kan", "last_name": "Yonemori", "name": null } ], "identifiers": { "doi": { "normalized": "10.1200/po-25-00907" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "42372207" } }, "mesh": [ { "descriptor": "Asian People", "descriptor_ui": "D044466", "major_topic": false }, { "descriptor": "Gene Expression Regulation, Neoplastic", "descriptor_ui": "D015972", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": true }, { "descriptor": "Neoplasms", "descriptor_ui": "D009369", "major_topic": true } ], "publication": { "conference_name": null, "date": "2026 Jun", "date_precision": "unknown", "issue": "6", "normalized_date": null, "pages": "e2500907", "proceedings_title": null, "publisher": "", "title": "JCO precision oncology", "volume": "10", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "Integrating DNA Mutations and RNA Expression of Cancer Driver Genes in Asian Rare Cancers: A Pan-Cancer Analysis.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "We have previously reported radiological patterns of precursor lesions of lung squamous cell carcinoma (SqCCs) using computed tomography. SqCCs were found to develop from five unique precursor patterns. We histologically analyzed 61 cases from the previous cohort to evaluate whether these precursor patterns reflect possible developmental pathways. Of the precursor patterns, the endobronchial group demonstrated involvement of large bronchi in the hilar region. In the subsolid nodule pattern group, which exhibited ground-glass opacities radiologically, the tumors showed intra-alveolar wall infiltration, nuclear inclusion/vacuoles, low mitotic count, and absent atypical mitosis. In two of the seven cases in this group, lepidic growth, corresponding to ground-glass opacity, occurred at the tumor periphery. In the cyst wall thickening group, the tumors were located subpleurally, characterized by papillary growth structures. In the multiple-nodule group, all tumors displayed elastofibrous collapse and intra-alveolar wall infiltration. Overall and recurrence-free survival varied across the progression patterns. The radiological progression patterns were reflected in the histological features, highlighting the unique characteristics of subsolid and multiple nodule groups corresponding to peripheral-type SqCC. This study represented a new approach to the assessment of tumor evolutional pathways with histological features in combination with temporal radiographic changes.", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Masahiro", "last_name": "Adachi", "name": null }, { "creator_type": "author", "first_name": "Jumpei", "last_name": "Kashima", "name": null }, { "creator_type": "author", "first_name": "Haruto", "last_name": "Sugawara", "name": null }, { "creator_type": "author", "first_name": "Satsuki", "last_name": "Kishikawa", "name": null }, { "creator_type": "author", "first_name": "Hirokazu", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Masaya", "last_name": "Yotsukura", "name": null }, { "creator_type": "author", "first_name": "Tomohiro", "last_name": "Haruki", "name": null }, { "creator_type": "author", "first_name": "Yukihiro", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Igaki", "name": null }, { "creator_type": "author", "first_name": "Shun-Ichi", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Masahiko", "last_name": "Kusumoto", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/pin.70124" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "42116637" } }, "mesh": [ { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Aged, 80 and over", "descriptor_ui": "D000369", "major_topic": false }, { "descriptor": "Carcinoma, Squamous Cell", "descriptor_ui": "D002294", "major_topic": true }, { "descriptor": "Disease Progression", "descriptor_ui": "D018450", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Lung Neoplasms", "descriptor_ui": "D008175", "major_topic": true }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Tomography, X-Ray Computed", "descriptor_ui": "D014057", "major_topic": false } ], "publication": { "conference_name": null, "date": "2026 May", "date_precision": "unknown", "issue": "5", "normalized_date": null, "pages": "e70124", "proceedings_title": null, "publisher": "", "title": "Pathology international", "volume": "76", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "Histological Features of Lung Squamous Cell Carcinoma According to Radiological Early-Phase Progression Patterns.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Polycythemia vera (PV) is a myeloproliferative neoplasm characterized by the clonal expansion of hematopoietic stem cells, commonly caused by pathogenic variants in Janus kinase 2 (JAK2). Although PV primarily affects the hematologic system, various renal manifestations have been reported, including rare cases of glomerulopathies. We describe a 73-year-old woman with PV harboring a JAK2 (V617F) mutation who developed hematuria, proteinuria, and renal dysfunction. Kidney biopsy revealed IgA nephropathy (IgAN) with cellular crescents. Because corticosteroid therapy was initially avoided due to concern for exacerbating PV, treatment was initiated with a JAK inhibitor, ruxolitinib. Over the following year, urinary protein levels decreased and serum creatinine stabilized, suggesting that JAK inhibition may have contributed to an improvement in IgAN activity. Two years of tapering corticosteroid therapy later resulted in clinical remission. To our knowledge, this is the first reported case of IgAN showing improvement after JAK inhibitor therapy in a patient with PV. Proposed mechanisms include suppression of IL-6/IL-11-driven platelet-derived growth factor production leading to reduced mesangial proliferation, and modulation of aberrant hematopoietic IgA production. This case suggests that JAK inhibition may not only normalize hematopoiesis in PV but also modify glomerular inflammation in IgAN, particularly in patients with hematologic comorbid conditions.", "classifications": [ { "id": "Nishikii", "label": "Group Nishikii", "parent": "Shintaku", "type": "group" }, { "id": "Shintaku", "label": "Team Shintaku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Mayumi", "last_name": "Takahashi-Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Hidekazu", "last_name": "Nishikii", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Shimizu", "name": null }, { "creator_type": "author", "first_name": "Yoko", "last_name": "Kaneko", "name": null }, { "creator_type": "author", "first_name": "Mamiko", "last_name": "Sakata-Yanagimoto", "name": null }, { "creator_type": "author", "first_name": "Joichi", "last_name": "Usui", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.xkme.2026.101376" }, "pmcid": { "normalized": "PMC13213300" }, "pmid": { "normalized": "42211688" } }, "mesh": [], "publication": { "conference_name": null, "date": "2026 Jul", "date_precision": "unknown", "issue": "7", "normalized_date": null, "pages": "101376", "proceedings_title": null, "publisher": "", "title": "Kidney medicine", "volume": "8", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "JAK Inhibitor-Induced Improvement of IgA Nephropathy in a Patient With Polycythemia Vera: A Case Report.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: T-cell immunoglobulin and mucin domain containing protein 4 (TIM4), a phosphatidylserine receptor primarily expressed on antigen-presenting cells, has been implicated in phagocytosis and immune regulation in various diseases, including malignancies. However, the significance of TIM4 in the breast cancer microenvironment remains unclear. In this study, we investigated the localization and clinical significance of TIM4 in breast cancer. METHODS: We immunolocalized TIM4 in human breast carcinoma tissues using immunohistochemistry (IHC) and multiplex fluorescence-immunohistochemistry (F-IHC) and examined its correlation with clinicopathological parameters and clinical outcomes. RESULTS: TIM4 was highly expressed in both carcinoma cells and stromal cells in human breast carcinoma tissues. Multiplex F-IHC revealed that TIM4 was co-localized with CD68, a macrophage marker, whereas no co-localization was observed between TIM4 and CD80 (an M1 macrophage marker) or CD163 (an M2 macrophage marker). Prognostic analysis of 171 breast carcinoma tissues by IHC revealed that infiltration of TIM4-positive stromal cells was associated with an aggressive tumor phenotype, including increased proliferative and invasive potential, as well as poorer clinical outcomes. In contrast, TIM4 immunoreactivity in carcinoma cells showed no significant correlation with clinical outcomes. CONCLUSIONS: These findings suggest that infiltration of TIM4-positive macrophages serves as a strong prognostic indicator in breast cancer and that TIM4 may represent a novel marker for tumor-promoting macrophages.", "classifications": [ { "id": "Suzuki", "label": "Group Suzuki", "parent": "Takekawa", "type": "group" }, { "id": "Takekawa", "label": "Team Takekawa", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Mio", "last_name": "Yamaguchi-Tanaka", "name": null }, { "creator_type": "author", "first_name": "Kiyoshi", "last_name": "Takagi", "name": null }, { "creator_type": "author", "first_name": "Miyu", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Ai", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Yuto", "last_name": "Yamazaki", "name": null }, { "creator_type": "author", "first_name": "Minoru", "last_name": "Miyashita", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Suzuki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/s12282-026-01825-8" }, "pmcid": { "normalized": "PMC12960482" }, "pmid": { "normalized": "41563642" } }, "mesh": [ { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Antigens, CD", "descriptor_ui": "D015703", "major_topic": false }, { "descriptor": "Biomarkers, Tumor", "descriptor_ui": "D014408", "major_topic": true }, { "descriptor": "Breast Neoplasms", "descriptor_ui": "D001943", "major_topic": true }, { "descriptor": "CD68 Molecule", "descriptor_ui": "D000097382", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Immunohistochemistry", "descriptor_ui": "D007150", "major_topic": false }, { "descriptor": "Macrophages", "descriptor_ui": "D008264", "major_topic": true }, { "descriptor": "Membrane Proteins", "descriptor_ui": "D008565", "major_topic": true }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Prognosis", "descriptor_ui": "D011379", "major_topic": false }, { "descriptor": "Tumor Microenvironment", "descriptor_ui": "D059016", "major_topic": false }, { "descriptor": "Tumor-Associated Macrophages", "descriptor_ui": "D000084582", "major_topic": true } ], "publication": { "conference_name": null, "date": "2026 Mar", "date_precision": "unknown", "issue": "2", "normalized_date": null, "pages": "436-447", "proceedings_title": null, "publisher": "", "title": "Breast cancer (Tokyo, Japan)", "volume": "33", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "Infiltration of TIM4-positive intratumoral macrophages serves as an adverse prognostic factor in breast cancer.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Live imaging data analysis often requires an objective, local, and accurate way of quantification of cell dynamics. In the research field of polarized tip-growth, the cell fluctuations and/or fluctuations in tip position and growth direction hamper automated analyses of huge amounts of imaging sequences. The fluctuated nature in data makes it unclear how cell shape and growth are linked to intracellular events that could be the actual driving force of cell growth. To overcome these difficulties, we developed a powerful and user-friendly tool called KymoTip with an available format. In this software, novel functions such as coordinate normalization, tip-bottom detection, and signal kymograph were implemented. We confirmed that not only plasma membrane-labeled fluorescent images, but also images such as bright-field and cortical microtubule markers-so long as the cell contours can be identified-are amenable to KymoTip. Furthermore, by combining markers for cell contours with those that visualize intracellular structures, it becomes possible to quantitatively analyze various intracellular events, such as nuclear migration and calcium wave, in conjunction with cellular growth dynamics. Since KymoTip can be handled by non-specialists, it is expected to promote understanding of what happens at the sub- and cellular level with high-throughput outcomes.", "classifications": [ { "id": "JPMJCR2121", "label": "JPMJCR2121", "researcher": "Minako Ueda", "type": "grant" }, { "id": "Tsugawa", "label": "Group Tsugawa", "parent": "Ueda", "type": "group" }, { "id": "Ueda", "label": "Group Ueda", "parent": "Ueda", "type": "group" }, { "id": "Ueda", "label": "Team Ueda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Zichen", "last_name": "Kang", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Kimata", "name": null }, { "creator_type": "author", "first_name": "Tomonobu", "last_name": "Nonoyama", "name": null }, { "creator_type": "author", "first_name": "Toru", "last_name": "Ikeuchi", "name": null }, { "creator_type": "author", "first_name": "Kazuyuki", "last_name": "Kuchitsu", "name": null }, { "creator_type": "author", "first_name": "Satoru", "last_name": "Tsugawa", "name": null }, { "creator_type": "author", "first_name": "Minako", "last_name": "Ueda", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/tpj.70691" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "41558033" } }, "mesh": [ { "descriptor": "Algorithms", "descriptor_ui": "D000465", "major_topic": false }, { "descriptor": "Arabidopsis", "descriptor_ui": "D017360", "major_topic": false }, { "descriptor": "Biomarkers", "descriptor_ui": "D015415", "major_topic": false }, { "descriptor": "Cell Proliferation", "descriptor_ui": "D049109", "major_topic": false }, { "descriptor": "Kymography", "descriptor_ui": "D007734", "major_topic": false }, { "descriptor": "Microtubules", "descriptor_ui": "D008870", "major_topic": false }, { "descriptor": "Plant Cells", "descriptor_ui": "D059828", "major_topic": true }, { "descriptor": "Plant Development", "descriptor_ui": "D063245", "major_topic": true }, { "descriptor": "Software", "descriptor_ui": "D012984", "major_topic": true } ], "publication": { "conference_name": null, "date": "2026 Jan", "date_precision": "unknown", "issue": "2", "normalized_date": null, "pages": "e70691", "proceedings_title": null, "publisher": "", "title": "The Plant journal : for cell and molecular biology", "volume": "125", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "KymoTip: high-throughput characterization of tip-growth dynamics in plant cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Patients with hypertension are recommended to decrease their salt intake. However, some patients do not follow this recommendation. It is possible that some of these individuals cannot restrict their salt intake due to a genetic preference for salt. Thus, we attempted to identify genetic factors related to salt restriction behavior. The subjects were 817 patients with hypertension. Salt restriction status was determined by self-reported answers (yes/no) to the question \"Do you restrict your salt intake in everyday meals?\" We focused on 21 single-nucleotide polymorphisms related to genes involved in the regulation of blood pressure, salt metabolism, or neurotransmission, and analyzed the associations of the single-nucleotide polymorphisms with salt restriction behavior. Of the 817 subjects, 568 (69.5%) reported that they restricted their salt intake. Two single-nucleotide polymorphisms (rs1167998 and rs2970847) were found to be correlated with salt restriction behavior. Among the 21 single-nucleotide polymorphisms, rs1167998 in the intron region of the dedicator of cytokinesis 7 gene, which encodes a guanine nucleotide exchange factor that plays a role in axon formation and neuronal polarization, showed the strongest association (odds ratio per allele, 1.48; 95% confidence interval, 1.11 to 1.95). In conclusion, rs1167998, a single-nucleotide polymorphism in the dedicator of cytokinesis 7 gene that is associated with blood lipid levels and cardiovascular disease risk was associated with salt restriction behavior in a population of Japanese patients with hypertension. Further confirmatory studies are warranted.", "classifications": [ { "id": "Tanaka", "label": "Group Tanaka", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Hideo", "last_name": "Nakane", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Tamura", "name": null }, { "creator_type": "author", "first_name": "Mako", "last_name": "Nagayoshi", "name": null }, { "creator_type": "author", "first_name": "Rieko", "last_name": "Okada", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Takeuchi", "name": null }, { "creator_type": "author", "first_name": "Yohko", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Sadao", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Naoyuki", "last_name": "Takashima", "name": null }, { "creator_type": "author", "first_name": "Teruhide", "last_name": "Koyama", "name": null }, { "creator_type": "author", "first_name": "Kokichi", "last_name": "Arisawa", "name": null }, { "creator_type": "author", "first_name": "Hiroaki", "last_name": "Ikezaki", "name": null }, { "creator_type": "author", "first_name": "Keitaro", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Daisaku", "last_name": "Nishimoto", "name": null }, { "creator_type": "author", "first_name": "Yukihide", "last_name": "Momozawa", "name": null }, { "creator_type": "author", "first_name": "Nobuyuki", "last_name": "Hamajima", "name": null }, { "creator_type": "author", "first_name": "Hideo", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Wakai", "name": null }, { "creator_type": "author", "first_name": "Keitaro", "last_name": "Matsuo", "name": null } ], "identifiers": { "doi": { "normalized": "10.18999/nagjms.88.2.217" }, "pmcid": { "normalized": "PMC13438822" }, "pmid": { "normalized": "42559087" } }, "mesh": [ { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Blood Pressure", "descriptor_ui": "D001794", "major_topic": false }, { "descriptor": "Diet, Sodium-Restricted", "descriptor_ui": "D004039", "major_topic": true }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Genetic Predisposition to Disease", "descriptor_ui": "D020022", "major_topic": false }, { "descriptor": "Guanine Nucleotide Exchange Factors", "descriptor_ui": "D020662", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Hypertension", "descriptor_ui": "D006973", "major_topic": true }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Polymorphism, Single Nucleotide", "descriptor_ui": "D020641", "major_topic": true }, { "descriptor": "Sodium Chloride, Dietary", "descriptor_ui": "D017673", "major_topic": false } ], "publication": { "conference_name": null, "date": "2026 May", "date_precision": "unknown", "issue": "2", "normalized_date": null, "pages": "217-231", "proceedings_title": null, "publisher": "", "title": "Nagoya journal of medical science", "volume": "88", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "A polymorphism in the DOCK7 gene (rs1167998) is associated with salt restriction behavior in hypertensive patients.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Artificial intelligence (AI) technologies are rapidly being introduced into the medical device field, particularly in the form of software as a medical device (AI-SaMD), for which regulatory approvals are increasing. In the United States and Europe, many approved AI-SaMD products have been implemented in medical imaging applications, such as computed tomography (CT) and magnetic resonance imaging (MRI). Similar trends are observed in Japan, where approved AI-SaMD products have been implemented for endoscopy, laparoscopy, and CT. In gastrointestinal endoscopy, several randomized controlled trials have demonstrated that AI-assisted systems improve adenoma detection rate and reduce miss rate, contributing to overall procedural quality. In diagnostic imaging, AI has been used to develop techniques that reduce radiation dose while maintaining diagnostic performance, and has also been explored for use in screening examinations. In surgical assistance, the integration of AI with extended reality (XR) technologies has enabled intraoperative visualization of anatomical structures and instrument tracking, offering novel strategies for navigation. In pathology, deep learning models have shown potential to predict molecular subtypes and treatment responsiveness in malignancies. Collectively, these findings indicate that medical AI is transitioning from research-based technologies toward clinical implementation and, in some domains, commercialization. Future challenges include standardization, explainability, and effective integration into clinical workflows to ensure safe and sustainable adoption.", "classifications": [ { "id": "Hamamoto", "label": "Group Hamamoto", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Tomonori", "last_name": "Taniguchi", "name": null }, { "creator_type": "author", "first_name": "Masaaki", "last_name": "Komatsu", "name": null }, { "creator_type": "author", "first_name": "Ryuji", "last_name": "Hamamoto", "name": null } ], "identifiers": { "doi": { "normalized": null }, "pmcid": { "normalized": null }, "pmid": { "normalized": "42551940" } }, "mesh": [ { "descriptor": "Artificial Intelligence", "descriptor_ui": "D001185", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Neoplasms", "descriptor_ui": "D009369", "major_topic": true } ], "publication": { "conference_name": null, "date": "2026 Jun", "date_precision": "unknown", "issue": "6", "normalized_date": null, "pages": "398-401", "proceedings_title": null, "publisher": "", "title": "Gan to kagaku ryoho. Cancer & chemotherapy", "volume": "53", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "[Frontiers in Research, Development, and Clinical Application of AI-SaMDs].", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Pancreatic cancers, whose incidence increases with age, are often refractory to treatment. Here, we identified a core mechanism shared by physiological homeostasis, senescent cell accumulation during aging, and pancreatic cancers. Pancreatic acinar cells, when stressed, secrete CXCL13, which protects stressed cells while transiently activating paracrine Hippo/YAP signaling to induce proliferation and PD-L1-mediated immune protection to maintain organ homeostasis. In the aged pancreas, CXCL13/YAP/PD-L1 signaling permits senescent cells to survive, driving feedforward chronic inflammation and steatosis. Because of prolonged CXCL13/YAP/PD-L1 activation in pancreatic cancers, neighboring noncancerous cells, activated for proliferation and immune-protected, eventually transform and accelerate tumor progression. CXCL13 blockade removed senescent cells and ameliorated steatosis in the aged pancreas while suppressing tumor growth in pancreatic cancer models, highlighting the CXCL13/YAP/PD-L1 axis as a potential therapeutic target. Together, our findings demonstrate the stress-induced CXCL13/YAP/PD-L1 axis as a central regulator of cell-state transitions in the pancreas, providing a unifying principle by which organ homeostasis, aging, and tumorigenesis are governed.", "classifications": [ { "id": "Yamamoto", "label": "Group Yamamoto", "parent": "Toyoshima", "type": "group" }, { "id": "Toyoshima", "label": "Team Toyoshima", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Masahiro", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Kenichiro", "last_name": "Furuyama", "name": null }, { "creator_type": "author", "first_name": "Keisuke", "last_name": "Sumide", "name": null }, { "creator_type": "author", "first_name": "Masashi", "last_name": "Horiguchi", "name": null }, { "creator_type": "author", "first_name": "Ahmed I.", "last_name": "Abo-Ahmed", "name": null }, { "creator_type": "author", "first_name": "Hirofumi", "last_name": "Shibata", "name": null }, { "creator_type": "author", "first_name": "Akito", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Ahmed M.", "last_name": "Rashwan", "name": null }, { "creator_type": "author", "first_name": "Toshihiko", "last_name": "Masui", "name": null }, { "creator_type": "author", "first_name": "Cantas", "last_name": "Alev", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Yasuhiro", "last_name": "Yamada", "name": null }, { "creator_type": "author", "first_name": "Shin", "last_name": "Kaneko", "name": null }, { "creator_type": "author", "first_name": "Shuh", "last_name": "Narumiya", "name": null }, { "creator_type": "author", "first_name": "David", "last_name": "Tuveson", "name": null }, { "creator_type": "author", "first_name": "Shinji", "last_name": "Uemoto", "name": null }, { "creator_type": "author", "first_name": "Etsuro", "last_name": "Hatano", "name": null }, { "creator_type": "author", "first_name": "Yoshiya", "last_name": "Kawaguchi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1126/sciadv.adu7865" }, "pmcid": { "normalized": "PMC13134631" }, "pmid": { "normalized": "42066078" } }, "mesh": [ { "descriptor": "Aging", "descriptor_ui": "D000375", "major_topic": true }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "B7-H1 Antigen", "descriptor_ui": "D060890", "major_topic": false }, { "descriptor": "Cellular Senescence", "descriptor_ui": "D016922", "major_topic": false }, { "descriptor": "Chemokine CXCL13", "descriptor_ui": "D054382", "major_topic": true }, { "descriptor": "Disease Progression", "descriptor_ui": "D018450", "major_topic": false }, { "descriptor": "Homeostasis", "descriptor_ui": "D006706", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Inflammation", "descriptor_ui": "D007249", "major_topic": true }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Pancreas, Exocrine", "descriptor_ui": "D046790", "major_topic": true }, { "descriptor": "Pancreatic Neoplasms", "descriptor_ui": "D010190", "major_topic": true }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false } ], "publication": { "conference_name": null, "date": "2026 May", "date_precision": "unknown", "issue": "18", "normalized_date": null, "pages": "eadu7865", "proceedings_title": null, "publisher": "", "title": "Science advances", "volume": "12", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "Stress-induced CXCL13 regulates pancreatic exocrine homeostasis, age-related chronic inflammation, and cancer progression.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "AIMS: Hypoxia-inducible factor (HIF) signalling influences cardiomyocyte differentiation, maturation, and metabolic adaptation under pathological conditions. HIF-Prolyl hydroxylase domain (HIF-PH) inhibitors, which target this pathway, have been introduced for the treatment of renal anaemia. Their precise effect or safety on cardiac function remains unclear because their pharmacokinetics and distribution are not well-understood. This study aimed to examine HIF signalling activation in adult cardiomyocytes (CMs). METHODS AND RESULTS: We used tamoxifen (TAM)-inducible, CM-specific von Hippel-Lindau (VHL) knockout (VHL-MCM) mice to activate CM HIF signalling. Then we subjected the mice to normal ageing or high-fat diet (HFD) and L-NAME feeding, a murine model of heart failure with preserved ejection fraction (HFpEF). In normal ageing group, there was no difference in the echocardiographic parameters or tissue fibrosis between VHL-MCM and control mice. VHL-MCM mice exhibited significantly increased capillary density and higher expression levels of HIF-target genes (P = 0.0248, two-way ANOVA). Under HFD + L-NAME treatment, VHL-MCM mice showed transient but significantly preserved global longitudinal strain (GLS) at 12 weeks post-TAM injection compared to controls (P = 0.0284, two-way ANOVA). Sirius red staining indicated a trend towards reduced whole-heart and interstitial fibrosis with significant increase in capillary density in VHL-MCM mice. CONCLUSION: Sustained HIF signalling activation in adult CM does not impair the cardiac structure and function in normal ageing process and shows transient yet beneficial effect in murine HFpEF model.", "classifications": [ { "id": "Kuchimaru", "label": "Group Kuchimaru", "parent": "Shintaku", "type": "group" }, { "id": "Shintaku", "label": "Team Shintaku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Daigo", "last_name": "Sawaki", "name": null }, { "creator_type": "author", "first_name": "Takayuki", "last_name": "Isagawa", "name": null }, { "creator_type": "author", "first_name": "Shigeru", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Tatsuyuki", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Hiroaki", "last_name": "Semba", "name": null }, { "creator_type": "author", "first_name": "Hiroki", "last_name": "Sugimoto", "name": null }, { "creator_type": "author", "first_name": "Kazutoshi", "last_name": "Ono", "name": null }, { "creator_type": "author", "first_name": "Ariunbold", "last_name": "Chuluun-Erdene", "name": null }, { "creator_type": "author", "first_name": "Thuc Toan", "last_name": "Pham", "name": null }, { "creator_type": "author", "first_name": "Ryohei", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Toshinaru", "last_name": "Kawakami", "name": null }, { "creator_type": "author", "first_name": "Masamichi", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Shun", "last_name": "Minatsuki", "name": null }, { "creator_type": "author", "first_name": "Yasutomi", "last_name": "Higashikuni", "name": null }, { "creator_type": "author", "first_name": "Masataka", "last_name": "Asagiri", "name": null }, { "creator_type": "author", "first_name": "Ichiro", "last_name": "Manabe", "name": null }, { "creator_type": "author", "first_name": "Takahide", "last_name": "Kohro", "name": null }, { "creator_type": "author", "first_name": "Takahiro", "last_name": "Kuchimaru", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Imai", "name": null }, { "creator_type": "author", "first_name": "Norihiko", "last_name": "Takeda", "name": null } ], "identifiers": { "doi": { "normalized": "10.1093/ehjopen/oeaf178" }, "pmcid": { "normalized": "PMC12825614" }, "pmid": { "normalized": "41585597" } }, "mesh": [], "publication": { "conference_name": null, "date": "2026 Jan", "date_precision": "unknown", "issue": "1", "normalized_date": null, "pages": "oeaf178", "proceedings_title": null, "publisher": "", "title": "European heart journal open", "volume": "6", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "Sustained HIF activation in adult cardiomyocytes show transient beneficial effect in murine HFpEF model.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Tissue homeostasis relies on the balance between proliferation of stem cells and death of differentiated cells. In Drosophila gut enterocytes, we recently identified a novel form of cell death, termed erebosis. Erebosis is a nonapoptotic, nonautophagic, and nonnecrotic process, in which affected cells accumulate Ance (angiotensin-converting enzyme) and lose many other proteins, ultimately leading to the loss of organelles and the nucleus. The underlying molecular mechanism of erebosis has remained unclear. Here, through single-cell RNA sequencing and genetic approaches, we found that the small metabolite heme regulates erebosis. Cells undergoing erebosis up-regulate the heme-degrading enzyme Heme oxygenase (Ho) and the heme exporter Mrp5, and decrease intracellular amounts of heme. Heme depletion by Mrp5 overexpression promotes erebosis, whereas heme accumulation by knockdown of Ho or Mrp5, or by feeding a heme precursor, suppresses it. Downstream of heme, Dpp signaling suppresses erebosis. Inhibition of erebosis reduces intestinal stem cell proliferation, indicating a cross-talk mechanism between enterocyte death and stem cell division. Our results demonstrate that reduction of cytoplasmic heme is a critical step in initiating enterocyte erebosis and coordinating stem cell proliferation, thereby maintaining gut tissue homeostasis. This work provides the first insight into the molecular mechanism regulating erebosis.", "classifications": [ { "id": "Nikaido", "label": "Group Nikaido", "parent": "Fujiwara", "type": "group" }, { "id": "Fujiwara", "label": "Team Fujiwara", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Motohiro", "last_name": "Morikawa", "name": null }, { "creator_type": "author", "first_name": "Tetsutaro", "last_name": "Hayashi", "name": null }, { "creator_type": "author", "first_name": "Yuko", "last_name": "Ikegawa", "name": null }, { "creator_type": "author", "first_name": "Tomomi", "last_name": "Takano", "name": null }, { "creator_type": "author", "first_name": "Kazuya", "last_name": "Wata", "name": null }, { "creator_type": "author", "first_name": "Hirohisa", "last_name": "Kyogoku", "name": null }, { "creator_type": "author", "first_name": "Mariko", "last_name": "Kuse", "name": null }, { "creator_type": "author", "first_name": "Mika", "last_name": "Yoshimura", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Nishida", "name": null }, { "creator_type": "author", "first_name": "Rahul", "last_name": "Parit", "name": null }, { "creator_type": "author", "first_name": "Dao My", "last_name": "Linh", "name": null }, { "creator_type": "author", "first_name": "Kanta", "last_name": "Kawai", "name": null }, { "creator_type": "author", "first_name": "Tasuku", "last_name": "Hirayama", "name": null }, { "creator_type": "author", "first_name": "Chun Wang", "last_name": "Sy", "name": null }, { "creator_type": "author", "first_name": "Kan", "last_name": "Etoh", "name": null }, { "creator_type": "author", "first_name": "Itoshi", "last_name": "Nikaido", "name": null }, { "creator_type": "author", "first_name": "Sa Kan", "last_name": "Yoo", "name": null } ], "identifiers": { "doi": { "normalized": "10.1371/journal.pbio.3003942" }, "pmcid": { "normalized": "PMC13489435" }, "pmid": { "normalized": "42616742" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Death", "descriptor_ui": "D016923", "major_topic": false }, { "descriptor": "Cell Proliferation", "descriptor_ui": "D049109", "major_topic": false }, { "descriptor": "Drosophila melanogaster", "descriptor_ui": "D004331", "major_topic": true }, { "descriptor": "Drosophila Proteins", "descriptor_ui": "D029721", "major_topic": false }, { "descriptor": "Enterocytes", "descriptor_ui": "D020895", "major_topic": true }, { "descriptor": "Heme", "descriptor_ui": "D006418", "major_topic": true }, { "descriptor": "Heme Oxygenase (Decyclizing)", "descriptor_ui": "D006419", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Stem Cells", "descriptor_ui": "D013234", "major_topic": false } ], "publication": { "conference_name": null, "date": "2026 Aug", "date_precision": "unknown", "issue": "8", "normalized_date": null, "pages": "e3003942", "proceedings_title": null, "publisher": "", "title": "PLoS biology", "volume": "24", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "Heme acts as a metabolic brake on erebosis in the Drosophila gut.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "SIGNIFICANCE: Cervical cancer progresses through cervical intraepithelial neoplasia (CIN), which are precursor lesions of cervical cancer. In low-grade CIN, atypical cells are generated inside the squamous epithelium, which causes the accuracy of cytodiagnosis for cervical cancer not to be very high. The grade of CIN can be estimated by the depth of atypical cell infiltration from the basal layer to the surface, rather than the abnormality of cells. Therefore, a noninvasive method is required to evaluate the depths of abnormal cells hidden at depth. AIM: Cancerous tissues beneath healthy tissues were experimentally identified using circularly polarized light scattering (CiPLS). This method enabled the changes in the size of the cell nuclei within the penetration depth in tissue to be investigated. APPROACH: Artificial unexposed cancerous tissues were prepared that consisted of healthy/cancerous/healthy layers with various thicknesses of the topmost healthy layer and the cancerous layer. A polarization imaging camera with a quarter-wave plate was used to create distribution images of the circular polarization of the scattered light. RESULTS: CiPLS images indicated that the thickness variation of the top healthy layer (the depth of the cancerous layer) caused significant changes in the degree of circular polarization. CONCLUSIONS: The depth of unexposed cancer lying within the optical penetration depth can be evaluated using a circular polarization imaging system based on the CiPLS method. These findings will lead to the development of a noninvasive optical diagnostic method for early-stage cervical cancer, potentially improving early detection and treatment outcomes.", "classifications": [ { "id": "Kuchimaru", "label": "Group Kuchimaru", "parent": "Shintaku", "type": "group" }, { "id": "Shintaku", "label": "Team Shintaku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Nozomi", "last_name": "Nishizawa", "name": null }, { "creator_type": "author", "first_name": "Mahiro", "last_name": "Ishikawa", "name": null }, { "creator_type": "author", "first_name": "Mike Raj", "last_name": "Maskey", "name": null }, { "creator_type": "author", "first_name": "Asato", "last_name": "Esumi", "name": null }, { "creator_type": "author", "first_name": "Toshihide", "last_name": "Matsumoto", "name": null }, { "creator_type": "author", "first_name": "Takahiro", "last_name": "Kuchimaru", "name": null } ], "identifiers": { "doi": { "normalized": "10.1117/1.jbo.31.2.027002" }, "pmcid": { "normalized": "PMC12880821" }, "pmid": { "normalized": "41657759" } }, "mesh": [ { "descriptor": "Cervix Uteri", "descriptor_ui": "D002584", "major_topic": false }, { "descriptor": "Early Detection of Cancer", "descriptor_ui": "D055088", "major_topic": true }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Light", "descriptor_ui": "D008027", "major_topic": false }, { "descriptor": "Microscopy, Polarization", "descriptor_ui": "D008859", "major_topic": false }, { "descriptor": "Optical Imaging", "descriptor_ui": "D061848", "major_topic": true }, { "descriptor": "Scattering, Radiation", "descriptor_ui": "D012542", "major_topic": false }, { "descriptor": "Uterine Cervical Dysplasia", "descriptor_ui": "D002578", "major_topic": false }, { "descriptor": "Uterine Cervical Neoplasms", "descriptor_ui": "D002583", "major_topic": true } ], "publication": { "conference_name": null, "date": "2026 Feb", "date_precision": "unknown", "issue": "2", "normalized_date": null, "pages": "027002", "proceedings_title": null, "publisher": "", "title": "Journal of biomedical optics", "volume": "31", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "Circularly polarized light scattering imaging of a cancerous layer creeping under a healthy layer for the diagnosis of early-stage cervical cancer.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "PURPOSE: To evaluate the clinical performance of \"Direct Strip PCR,\" a multiplex solid-phase real-time polymerase chain reaction (PCR) kit, for diagnosing infectious uveitis. STUDY DESIGN: Multicenter, prospective, diagnostic accuracy study METHODS: We analyzed 475 ocular-fluid samples (336 aqueous humor and 139 vitreous fluid) from 29 sites in Japan. Direct Strip PCR, an IVD-grade multiplex real-time PCR kit targeting HSV-1, HSV-2, VZV, EBV, CMV, HHV-6, HTLV-1, Toxoplasma gondii, and Treponema pallidum requiring no DNA extraction and incorporating internal controls, was compared with quantitative PCR (qPCR) for concordance and DNA copy-number correlation. RESULTS: All 9 of the target pathogens were detected. Direct Strip PCR showed excellent agreement with qPCR, with percent positive agreement (PPA), percent negative agreement (PNA), and percent overall agreement (POA) in aqueous humor of 98.0%, 99.2%, and 98.5%, respectively, and in vitreous fluid of 95.7%, 97.1%, and 96.4%, respectively, indicating high concordance for positive and negative results. All the values exceeded predefined 90% thresholds agreed upon with the Pharmaceuticals and Medical Devices Agency, meeting the required performance criteria. Discordant results were infrequent (10/4275 targets) and involved low-copy samples near the detection limit. The DNA copy numbers correlated strongly between the methods (r = 0.948-0.996). No adverse events were reported. CONCLUSION: Direct Strip PCR demonstrated high concordance with qPCR, reliably detected major pathogens of infectious uveitis, and yielded quantitative results that correlated with the qPCR results, supporting disease monitoring. Its solid-phase, extraction-free, and per-run calibration-free format provides a practical basis for regulatory submissions and global dissemination of multiplex PCR.", "classifications": [ { "id": "Suzuki", "label": "Group Suzuki", "parent": "Takekawa", "type": "group" }, { "id": "Takekawa", "label": "Team Takekawa", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Satoko", "last_name": "Nakano", "name": null }, { "creator_type": "author", "first_name": "Sunao", "last_name": "Sugita", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Takase", "name": null }, { "creator_type": "author", "first_name": "Yasuhiro", "last_name": "Tomaru", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Todokoro", "name": null }, { "creator_type": "author", "first_name": "Yumi", "last_name": "Hasegawa", "name": null }, { "creator_type": "author", "first_name": "Yasuhiro", "last_name": "Ikeda", "name": null }, { "creator_type": "author", "first_name": "Go", "last_name": "Mawatari", "name": null }, { "creator_type": "author", "first_name": "Chie", "last_name": "Sotozono", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Nagata", "name": null }, { "creator_type": "author", "first_name": "Kaoru", "last_name": "Araki-Sasaki", "name": null }, { "creator_type": "author", "first_name": "Suguru", "last_name": "Nakagawa", "name": null }, { "creator_type": "author", "first_name": "Yoshiaki", "last_name": "Kiuchi", "name": null }, { "creator_type": "author", "first_name": "Kaori", "last_name": "Mitoma", "name": null }, { "creator_type": "author", "first_name": "Nobuyo", "last_name": "Yawata", "name": null }, { "creator_type": "author", "first_name": "Takehiro", "last_name": "Hariya", "name": null }, { "creator_type": "author", "first_name": "Eiichi", "last_name": "Uchio", "name": null }, { "creator_type": "author", "first_name": "Tomoko", "last_name": "Tsukahara-Kawamura", "name": null }, { "creator_type": "author", "first_name": "Hidenori", "last_name": "Inoue", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Toriyama", "name": null }, { "creator_type": "author", "first_name": "Sentaro", "last_name": "Kusuhara", "name": null }, { "creator_type": "author", "first_name": "Wataru", "last_name": "Matsumiya", "name": null }, { "creator_type": "author", "first_name": "Nobuyuki", "last_name": "Ohguro", "name": null }, { "creator_type": "author", "first_name": "Hisashi", "last_name": "Mashimo", "name": null }, { "creator_type": "author", "first_name": "Ken", "last_name": "Fukuda", "name": null }, { "creator_type": "author", "first_name": "Waka", "last_name": "Ishida", "name": null }, { "creator_type": "author", "first_name": "Mariko", "last_name": "Egawa", "name": null }, { "creator_type": "author", "first_name": "Kei", "last_name": "Nakai", "name": null }, { "creator_type": "author", "first_name": "Masakazu", "last_name": "Morioka", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Hayashi", "name": null }, { "creator_type": "author", "first_name": "Tomoko", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Yoshihiko", "last_name": "Usui", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Goto", "name": null }, { "creator_type": "author", "first_name": "Ryohei", "last_name": "Nejima", "name": null }, { "creator_type": "author", "first_name": "Kazunori", "last_name": "Miyata", "name": null }, { "creator_type": "author", "first_name": "Kenichi", "last_name": "Namba", "name": null }, { "creator_type": "author", "first_name": "Keitaro", "last_name": "Hase", "name": null }, { "creator_type": "author", "first_name": "Annabelle A.", "last_name": "Okada", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Keino", "name": null }, { "creator_type": "author", "first_name": "Nobuhisa", "last_name": "Mizuki", "name": null }, { "creator_type": "author", "first_name": "Masaki", "last_name": "Takeuchi", "name": null }, { "creator_type": "author", "first_name": "Dai", "last_name": "Miyazaki", "name": null }, { "creator_type": "author", "first_name": "Kunihiro", "last_name": "Kiyosaki", "name": null }, { "creator_type": "author", "first_name": "Reiko", "last_name": "Kinouchi", "name": null }, { "creator_type": "author", "first_name": "Ryoji", "last_name": "Yanai", "name": null }, { "creator_type": "author", "first_name": "Sho-Hei", "last_name": "Uchi", "name": null }, { "creator_type": "author", "first_name": "Shigeko", "last_name": "Yashiro", "name": null }, { "creator_type": "author", "first_name": "Rie", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Aika", "last_name": "Tsutsui", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Yukiko", "last_name": "Umeki", "name": null }, { "creator_type": "author", "first_name": "Takaaki", "last_name": "Yahiro", "name": null }, { "creator_type": "author", "first_name": "Akane", "last_name": "Sonezaki", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Matsumoto", "name": null }, { "creator_type": "author", "first_name": "Tetsuji", "last_name": "Ohyama", "name": null }, { "creator_type": "author", "first_name": "Masae", "last_name": "Kuranari", "name": null }, { "creator_type": "author", "first_name": "Naoto", "last_name": "Uemura", "name": null }, { "creator_type": "author", "first_name": "Yuichi", "last_name": "Hori", "name": null }, { "creator_type": "author", "first_name": "Atsunobu", "last_name": "Takeda", "name": null }, { "creator_type": "author", "first_name": "Toshiaki", "last_name": "Kubota", "name": null }, { "creator_type": "author", "first_name": "Toshikatsu", "last_name": "Kaburaki", "name": null }, { "creator_type": "author", "first_name": "Koh-Hei", "last_name": "Sonoda", "name": null }, { "creator_type": "author", "first_name": "Manabu", "last_name": "Mochizuki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/s10384-026-01343-2" }, "pmcid": { "normalized": "PMC13452761" }, "pmid": { "normalized": "41926010" } }, "mesh": [ { "descriptor": "Aqueous Humor", "descriptor_ui": "D001082", "major_topic": true }, { "descriptor": "DNA, Bacterial", "descriptor_ui": "D004269", "major_topic": false }, { "descriptor": "DNA, Viral", "descriptor_ui": "D004279", "major_topic": true }, { "descriptor": "Eye Infections", "descriptor_ui": "D015817", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Multiplex Polymerase Chain Reaction", "descriptor_ui": "D060885", "major_topic": true }, { "descriptor": "Prospective Studies", "descriptor_ui": "D011446", "major_topic": false }, { "descriptor": "Real-Time Polymerase Chain Reaction", "descriptor_ui": "D060888", "major_topic": true }, { "descriptor": "Reproducibility of Results", "descriptor_ui": "D015203", "major_topic": false }, { "descriptor": "Uveitis", "descriptor_ui": "D014605", "major_topic": true }, { "descriptor": "Vitreous Body", "descriptor_ui": "D014822", "major_topic": false } ], "publication": { "conference_name": null, "date": "2026 Jul", "date_precision": "unknown", "issue": "4", "normalized_date": null, "pages": "966-982", "proceedings_title": null, "publisher": "", "title": "Japanese journal of ophthalmology", "volume": "70", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "Clinical performance of the multiplex solid-phase \"Direct Strip PCR\" for infectious uveitis: a multicenter diagnostic accuracy study.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Identifying regulatory relationships between transcription factors (TFs) and genes is essential to understand diverse biological phenomena related to gene expression. Recently, deep learning-based models to predict TFs that bind to genes from nucleotide sequences of the target genes have been developed, yet these models are trained to predict known TFs only. Here, we developed a deep learning model, GReNIMJA (Gene Regulatory Network Inference by Mixing and Jointing features of Amino acid and nucleotide sequences), to predict gene regulation even by unknown TFs. Our model is designed to mix the features of the TF amino acid sequences and nucleotide sequences of the target genes using a 2D Long Short-Term Memory architecture and to perform binary classification with the aim of determining the presence or absence of a regulatory relationship. By explicitly modeling interactions between TFs and genes, our model can predict gene regulation for unknown TFs. The accuracy of our model in predicting regulatory relationships was 84.4% for known TFs (higher than those of conventional models) and 68.5% for unknown TFs; the latter is an unsolved task for conventional deep learning-based models. We expect our model to advance identification of unknown gene regulatory networks and contribute to the understanding of diverse biological phenomena.", "classifications": [ { "id": "Kobayashi", "label": "Group Kobayashi", "parent": "Wakamoto", "type": "group" }, { "id": "Wakamoto", "label": "Team Wakamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Risa", "last_name": "Okubo", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Morikura", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Hiki", "name": null }, { "creator_type": "author", "first_name": "Yuta", "last_name": "Tokuoka", "name": null }, { "creator_type": "author", "first_name": "Tetsuya J.", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Takahiro G.", "last_name": "Yamada", "name": null }, { "creator_type": "author", "first_name": "Akira", "last_name": "Funahashi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1093/nargab/lqag022" }, "pmcid": { "normalized": "PMC12954442" }, "pmid": { "normalized": "41782896" } }, "mesh": [ { "descriptor": "Amino Acid Sequence", "descriptor_ui": "D000595", "major_topic": false }, { "descriptor": "Computational Biology", "descriptor_ui": "D019295", "major_topic": false }, { "descriptor": "Deep Learning", "descriptor_ui": "D000077321", "major_topic": true }, { "descriptor": "Gene Expression Regulation", "descriptor_ui": "D005786", "major_topic": true }, { "descriptor": "Gene Regulatory Networks", "descriptor_ui": "D053263", "major_topic": true }, { "descriptor": "Long Short Term Memory", "descriptor_ui": "D000098417", "major_topic": false }, { "descriptor": "Prediction Algorithms", "descriptor_ui": "D000098437", "major_topic": false }, { "descriptor": "Predictive Learning Models", "descriptor_ui": "D000098412", "major_topic": false }, { "descriptor": "Transcription Factors", "descriptor_ui": "D014157", "major_topic": true } ], "publication": { "conference_name": null, "date": "2026 Mar", "date_precision": "unknown", "issue": "1", "normalized_date": null, "pages": "lqag022", "proceedings_title": null, "publisher": "", "title": "NAR genomics and bioinformatics", "volume": "8", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "Mixing features of transcription factors and genes enable accurate prediction of gene regulation relationships for unknown transcription factors.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "We report the first case of bilateral malignant ciliary body medulloepithelioma (CBME) in an adult, with comprehensive histopathological and genomic analyses. The right eye harbored a malignant teratoid CBME with sarcomatous elements, while the left eye showed a non-teratoid variant. Whole-exome sequencing revealed shared chromosomal losses and additional aberrations in the teratoid tumor. No pathogenic germline mutations were identified. These findings suggest a potential correlation between histological subtype and genomic complexity in CBME.", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yuto", "last_name": "Kaimi", "name": null }, { "creator_type": "author", "first_name": "Shigenobu", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Toshihide", "last_name": "Ueno", "name": null }, { "creator_type": "author", "first_name": "Yukiko", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Hideki", "last_name": "Tsuji", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Mano", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null }, { "creator_type": "author", "first_name": "Taisuke", "last_name": "Mori", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/pin.70086" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "41560637" } }, "mesh": [ { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Ciliary Body", "descriptor_ui": "D002924", "major_topic": true }, { "descriptor": "Exome Sequencing", "descriptor_ui": "D000073359", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Neuroectodermal Tumors, Primitive", "descriptor_ui": "D018242", "major_topic": true }, { "descriptor": "Uveal Neoplasms", "descriptor_ui": "D014604", "major_topic": true } ], "publication": { "conference_name": null, "date": "2026 Jan", "date_precision": "unknown", "issue": "1", "normalized_date": null, "pages": "e70086", "proceedings_title": null, "publisher": "", "title": "Pathology international", "volume": "76", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "Late-Onset Bilateral Malignant Ciliary Body Medulloepithelioma in an Adult.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "SGLT2 inhibitors are widely used to treat patients with chronic heart failure, and several studies have shown that the efficacy of SGLT2 inhibitors also extends to acute heart failure. However, the mechanisms remain unknown. Here, using knockout mice and pharmacological approaches, we show that short-term SGLT2 inhibitor treatment activates hypoxia-inducible factor-1alpha (HIF-1alpha) signaling in cardiomyocytes, and further pharmacological studies raised the possibility that this effect is mediated by ketone body-derived succinate. One week of Dapagliflozin administration upregulated the expression of HIF-1alpha target genes, and the effect was abolished in cardiomyocyte-specific HIF-1alpha knockout mice. Metabolome analysis and enzyme-based assays revealed that, following one week of short-term Dapagliflozin treatment, ketone body levels in the heart increased, leading to an accumulation of succinate, which may act as a signaling metabolite that stabilizes HIF-1alpha. Administration of pimozide, which is a succinyl-CoA:3-ketoacid CoA transferase (SCOT) inhibitor that inhibits ketone body metabolism, abolished dapagliflozin-elicited activation of HIF-1alpha signaling. These results, although not conclusive, can be plausibly explained if short-term Dapagliflozin treatment activates HIF-1alpha signaling in cardiomyocytes via ketone body-derived succinate. Our study raises the possibility that HIF-1alpha plays a role in the effects of SGLT2 inhibitors and highlights HIF-1alpha as a speculative target for future studies.", "classifications": [ { "id": "Kuchimaru", "label": "Group Kuchimaru", "parent": "Shintaku", "type": "group" }, { "id": "Shintaku", "label": "Team Shintaku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Tatsuyuki", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Takayuki", "last_name": "Isagawa", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Sugiura", "name": null }, { "creator_type": "author", "first_name": "Daigo", "last_name": "Sawaki", "name": null }, { "creator_type": "author", "first_name": "Yu", "last_name": "Nakagama", "name": null }, { "creator_type": "author", "first_name": "Takahiro", "last_name": "Kuchimaru", "name": null }, { "creator_type": "author", "first_name": "Shun", "last_name": "Minatsuki", "name": null }, { "creator_type": "author", "first_name": "Shigeru", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Kazutoshi", "last_name": "Ono", "name": null }, { "creator_type": "author", "first_name": "Ariunbold", "last_name": "Chuluun-Erdene", "name": null }, { "creator_type": "author", "first_name": "Hiroaki", "last_name": "Semba", "name": null }, { "creator_type": "author", "first_name": "Masamichi", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Toshinaru", "last_name": "Kawakami", "name": null }, { "creator_type": "author", "first_name": "Ryohei", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Masaya", "last_name": "Sakamoto", "name": null }, { "creator_type": "author", "first_name": "Masataka", "last_name": "Asagiri", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Harada", "name": null }, { "creator_type": "author", "first_name": "Christian", "last_name": "Stockmann", "name": null }, { "creator_type": "author", "first_name": "Tomo", "last_name": "Yonezawa", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Hirota", "name": null }, { "creator_type": "author", "first_name": "Yasutoshi", "last_name": "Kido", "name": null }, { "creator_type": "author", "first_name": "Kinya", "last_name": "Otsu", "name": null }, { "creator_type": "author", "first_name": "Takahide", "last_name": "Kohro", "name": null }, { "creator_type": "author", "first_name": "Ichiro", "last_name": "Manabe", "name": null }, { "creator_type": "author", "first_name": "Issei", "last_name": "Komuro", "name": null }, { "creator_type": "author", "first_name": "Norihiko", "last_name": "Takeda", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.jphs.2026.01.008" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "41795960" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Benzhydryl Compounds", "descriptor_ui": "D001559", "major_topic": true }, { "descriptor": "Glucosides", "descriptor_ui": "D005960", "major_topic": true }, { "descriptor": "Hypoxia-Inducible Factor 1, alpha Subunit", "descriptor_ui": "D051795", "major_topic": true }, { "descriptor": "Ketone Bodies", "descriptor_ui": "D007657", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Myocytes, Cardiac", "descriptor_ui": "D032383", "major_topic": true }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": true }, { "descriptor": "Sodium-Glucose Transporter 2 Inhibitors", "descriptor_ui": "D000077203", "major_topic": true }, { "descriptor": "Succinic Acid", "descriptor_ui": "D019802", "major_topic": true } ], "publication": { "conference_name": null, "date": "2026 Apr", "date_precision": "unknown", "issue": "4", "normalized_date": null, "pages": "221-231", "proceedings_title": null, "publisher": "", "title": "Journal of pharmacological sciences", "volume": "160", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "Sodium-glucose Co-transporter 2 (SGLT2) inhibitor dapagliflozin acutely activates cardiomyocyte HIF-1alpha signaling via succinate, a signaling metabolite.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "OBJECTIVE: Whether the indications for wedge resection can be extended to early-stage non-small cell lung cancer (NSCLC) remains unclear. We investigated the survival outcomes and nodal involvement of ground-glass-opacity-dominant stage IA NSCLC undergoing wedge resection, segmentectomy, or lobectomy. METHODS: We retrospectively investigated the prognostic and clinicopathological outcomes of patients who underwent lung resection for ground-glass-opacity-dominant clinical stage IA (diameter /= 1%) in 33% of cases. The combined positive score for programmed death-ligand 1 was positive in 52% of programmed death-ligand 1 tumor proportion score-negative samples. In conclusion, CD79B and CD19 were variably expressed in CD20-negative large B-cell lymphomas, but lower in de novo DLBCL, and especially in plasmablastic lymphoma. Programmed cell death protein 1/programmed death-ligand one inhibitors may represent a treatment option.", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yuto", "last_name": "Kaimi", "name": null }, { "creator_type": "author", "first_name": "Yuka", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Mai", "last_name": "Takeuchi", "name": null }, { "creator_type": "author", "first_name": "Tetsuro", "last_name": "Ochi", "name": null }, { "creator_type": "author", "first_name": "Shinichi", "last_name": "Makita", "name": null }, { "creator_type": "author", "first_name": "Noriko", "last_name": "Iwaki", "name": null }, { "creator_type": "author", "first_name": "Suguru", "last_name": "Fukuhara", "name": null }, { "creator_type": "author", "first_name": "Wataru", "last_name": "Munakata", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Izutsu", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null }, { "creator_type": "author", "first_name": "Akiko Miyagi", "last_name": "Maeshima", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/hon.70173" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "41689301" } }, "mesh": [ { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Aged, 80 and over", "descriptor_ui": "D000369", "major_topic": false }, { "descriptor": "Antigens, CD19", "descriptor_ui": "D018941", "major_topic": true }, { "descriptor": "Antigens, CD20", "descriptor_ui": "D018951", "major_topic": true }, { "descriptor": "B7-H1 Antigen", "descriptor_ui": "D060890", "major_topic": true }, { "descriptor": "Biomarkers, Tumor", "descriptor_ui": "D014408", "major_topic": false }, { "descriptor": "CD79 Antigens", "descriptor_ui": "D051925", "major_topic": true }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Lymphoma, Large B-Cell, Diffuse", "descriptor_ui": "D016403", "major_topic": true }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Rituximab", "descriptor_ui": "D000069283", "major_topic": false } ], "publication": { "conference_name": null, "date": "2026 Mar", "date_precision": "unknown", "issue": "2", "normalized_date": null, "pages": "e70173", "proceedings_title": null, "publisher": "", "title": "Hematological oncology", "volume": "44", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "Differential Expression of CD79B, CD19, and PD-L1 in de Novo and Transformed CD20-Negative Large B-Cell Lymphomas.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "INTRODUCTION: Effective predictors of response to atezolizumab plus carboplatin/etoposide (CE) therapy in extensive-stage SCLC (ES-SCLC) remain limited. This exploratory analysis from J-TAIL-2 aimed to identify markers of survival benefit with atezolizumab plus CE therapy in ES-SCLC. METHODS: J-TAIL-2 (ClinicalTrials.gov ID, NCT04501497) was a multicenter observational study that enrolled patients receiving atezolizumab plus CE (ES-SCLC cohort) in clinical practice in Japan per local label and treatment guidelines. In this exploratory analysis, the association of CD8+ tumor-infiltrating lymphocyte (TIL) density and SCLC subtypes (SCLC-A [ASCL1 dominant], SCLC-N [NEUROD1 dominant], SCLC-P [ASCL1/NEUROD1 double-negative with POU2F3 expression], and SCLC-O [ASCL1/NEUROD1 double-negative not otherwise specified]) with overall survival (OS) and progression-free survival (PFS) was evaluated. SCLC subtyping was performed by immunohistochemistry. RESULTS: SCLC samples (n = 100; data cutoff, February 3, 2023) were categorized as SCLC-A (73%), SCLC-N (16%), SCLC-P (8%), and SCLC-O (3%). Among 96 patients who received first-line atezolizumab plus CE, median age was 72 (range, 39-87) years and 81% were male. Furthermore, 56 patients were classified into the CD8+ TIL-high subgroup and 40 into the TIL-low subgroup. Median (m)PFS with atezolizumab plus CE was 6.1 months (95% confidence interval [CI]: 4.5-7.5) in the TIL-high versus 4.4 months (95% CI: 4.0-5.1) in the TIL-low subgroup (p = 0.01); mOS was 18.4 (95% CI: 11.8-not estimable) versus 10.8 months (95% CI: 7.7-16.2; p = 0.04). mOS and mPFS were not significantly different between SCLC subtypes but were numerically shorter in the SCLC-N group. CONCLUSIONS: CD8+ TIL density is a potential biomarker of clinical benefit in ES-SCLC and may facilitate patient selection for atezolizumab combination therapy.", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Masayuki", "last_name": "Shirasawa", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Nishio", "name": null }, { "creator_type": "author", "first_name": "Kadoaki", "last_name": "Ohashi", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Osoegawa", "name": null }, { "creator_type": "author", "first_name": "Eiki", "last_name": "Kikuchi", "name": null }, { "creator_type": "author", "first_name": "Hideharu", "last_name": "Kimura", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Goto", "name": null }, { "creator_type": "author", "first_name": "Junichi", "last_name": "Shimizu", "name": null }, { "creator_type": "author", "first_name": "Eisaku", "last_name": "Miyauchi", "name": null }, { "creator_type": "author", "first_name": "Hiroshige", "last_name": "Yoshioka", "name": null }, { "creator_type": "author", "first_name": "Ichiro", "last_name": "Yoshino", "name": null }, { "creator_type": "author", "first_name": "Toshihiro", "last_name": "Misumi", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Jumpei", "last_name": "Kashima", "name": null }, { "creator_type": "author", "first_name": "Masahide", "last_name": "Oki", "name": null }, { "creator_type": "author", "first_name": "Hisao", "last_name": "Ashimura", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Misa", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Akihiko", "last_name": "Gemma", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.jtocrr.2025.100926" }, "pmcid": { "normalized": "PMC12955677" }, "pmid": { "normalized": "41783745" } }, "mesh": [], "publication": { "conference_name": null, "date": "2026 Mar", "date_precision": "unknown", "issue": "3", "normalized_date": null, "pages": "100926", "proceedings_title": null, "publisher": "", "title": "JTO clinical and research reports", "volume": "7", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "Potential Immune Microenvironment Biomarkers in SCLC: J-TAIL-2 Observational Study.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "We construct a mathematical model for a diffusiophoretic motion of a deformable droplet, which is floating at a liquid surface and is driven by the surface tension gradient originating from the surface concentration field of the chemicals that are emitted from the droplet. We define the free energy of the system by including the surface and line energies. From the calculation of the functional of the free energy, we obtain a mathematical model for the diffusiophoretic motion with deformation. By only considering the deformation of the second mode, we explicitly derive the time-evolution equations for the translational motion and the elliptic deformation. There are three stable states: an immobile circular droplet, an immobile elliptically deformed droplet, and a mobile droplet with the elliptic deformation in which the minor axis meets the motion direction, and we discuss the transition between these three stable states.", "classifications": [ { "id": "Nagayama", "label": "Group Nagayama", "parent": "Fujiwara", "type": "group" }, { "id": "Fujiwara", "label": "Team Fujiwara", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Kitahata", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Koyano", "name": null }, { "creator_type": "author", "first_name": "Yasuaki", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Masaharu", "last_name": "Nagayama", "name": null } ], "identifiers": { "doi": { "normalized": "10.1103/jv8k-rkx4" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "41998957" } }, "mesh": [], "publication": { "conference_name": null, "date": "2026 Mar", "date_precision": "unknown", "issue": "3-2", "normalized_date": null, "pages": "035408", "proceedings_title": null, "publisher": "", "title": "Physical review. E", "volume": "113", "year": 2026 }, "ssbd": { "database": [], "repository": [] }, "title": "Energetics-based model for a diffusiophoretic motion of a deformable droplet.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Lipid droplets (LDs) are vital organelles that govern energy storage and lipid metabolism in cells. The ability to direct the self-assembly of small molecules into defined nanostructures within LDs would provide opportunities to modulate their functions. Although supramolecular polymerization has been extensively investigated in low-polarity media, achieving controlled molecular assembly in neutral lipid droplets remains a formidable challenge. Here, we report the design of a lipophilic donor-acceptor-type fluorophore bearing phenylalanine-derived diamide units, which undergoes controlled supramolecular polymerization in the neutral lipid triolein. In triolein, the molecule assembles into fibrous aggregates that display intense fluorescence and a pronounced Cotton effect in circular dichroism spectrum. Spectroscopic and microscopic analyses reveal that a seeding strategy accelerates the conversion from a kinetically trapped monomeric state to fibrous assemblies. Furthermore, fluorescence imaging in artificial LDs demonstrates that aggregate size can be tuned through the seeding process.", "classifications": [ { "id": "Sato", "label": "Group Sato", "parent": "Tsuchiya", "type": "group" }, { "id": "Tsuchiya", "label": "Team Tsuchiya", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Miku", "last_name": "Naruse", "name": null }, { "creator_type": "author", "first_name": "Soichiro", "last_name": "Ogi", "name": null }, { "creator_type": "author", "first_name": "Keiji", "last_name": "Kajiwara", "name": null }, { "creator_type": "author", "first_name": "Natsumi", "last_name": "Fukaya", "name": null }, { "creator_type": "author", "first_name": "Yoshikatsu", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Masayasu", "last_name": "Taki", "name": null }, { "creator_type": "author", "first_name": "Shigehiro", "last_name": "Yamaguchi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/smll.202513411" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "41457813" } }, "mesh": [ { "descriptor": "Circular Dichroism", "descriptor_ui": "D002942", "major_topic": false }, { "descriptor": "Fluorescent Dyes", "descriptor_ui": "D005456", "major_topic": true }, { "descriptor": "Kinetics", "descriptor_ui": "D007700", "major_topic": false }, { "descriptor": "Lipid Droplets", "descriptor_ui": "D066292", "major_topic": true }, { "descriptor": "Phenylalanine", "descriptor_ui": "D010649", "major_topic": true } ], "publication": { "conference_name": null, "date": "2025 Dec 29", "date_precision": "day", "issue": "", "normalized_date": "2025-12-29", "pages": "e13411", "proceedings_title": null, "publisher": "", "title": "Small (Weinheim an der Bergstrasse, Germany)", "volume": "", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Kinetically Controlled Self-Assembly of a Lipophilic Fluorophore with Phenylalanine-Based Diamides in Artificial Lipid Droplets.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Blood vessels undergo extensive remodelling to acquire appropriate diameters, yet how endothelial cells coordinate changes in their number and shape to achieve this remains unclear. Here we show that endothelial cell contraction and rearrangements underlie the inverse relationship between cell number and vessel diameter during development. Using high-resolution imaging and manipulation of actin cytoskeleton organisation, in vivo laser ablation experiments and mathematical simulations, we reveal that tension-bearing, circumferential actomyosin bundles form in the endothelial cortex to drive endothelial cell contraction and vessel constriction. The anchorage of circumferential actin bundles to cell-cell junctions is mediated by Ccm1/Krit1 protein. Importantly, the loss of circumferential actin bundles in ccm1-deficient endothelial cells causes cell enlargement and impaired vessel constriction, culminating in vessel dilation characteristic of cerebral cavernous malformations. Our multiscale study demonstrates how circumferential actomyosin-driven endothelial cell contractions regulate vessel diameter and provides insights into mechanisms of both normal vascular development and disease pathogenesis.", "classifications": [ { "id": "Okuda", "label": "Group Okuda", "parent": "Imayoshi", "type": "group" }, { "id": "Imayoshi", "label": "Team Imayoshi", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yan", "last_name": "Chen", "name": null }, { "creator_type": "author", "first_name": "Nuria", "last_name": "Taberner", "name": null }, { "creator_type": "author", "first_name": "Jason", "last_name": "da Silva", "name": null }, { "creator_type": "author", "first_name": "Vivek", "last_name": "Semwal", "name": null }, { "creator_type": "author", "first_name": "Biplab", "last_name": "Bhattacherjee", "name": null }, { "creator_type": "author", "first_name": "Julia", "last_name": "Eckert", "name": null }, { "creator_type": "author", "first_name": "Igor", "last_name": "Kondrychyn", "name": null }, { "creator_type": "author", "first_name": "Mingzhao", "last_name": "Hu", "name": null }, { "creator_type": "author", "first_name": "Nitish", "last_name": "Aswani", "name": null }, { "creator_type": "author", "first_name": "Guihua", "last_name": "Chen", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Okada", "name": null }, { "creator_type": "author", "first_name": "Anne Karine", "last_name": "Lagendijk", "name": null }, { "creator_type": "author", "first_name": "Tatsuo", "last_name": "Shibata", "name": null }, { "creator_type": "author", "first_name": "Satoru", "last_name": "Okuda", "name": null }, { "creator_type": "author", "first_name": "Li-Kun", "last_name": "Phng", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41467-025-67820-3" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "41455707" } }, "mesh": [ { "descriptor": "Actin Cytoskeleton", "descriptor_ui": "D008841", "major_topic": false }, { "descriptor": "Actins", "descriptor_ui": "D000199", "major_topic": false }, { "descriptor": "Actomyosin", "descriptor_ui": "D000205", "major_topic": true }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Blood Vessels", "descriptor_ui": "D001808", "major_topic": true }, { "descriptor": "Endothelial Cells", "descriptor_ui": "D042783", "major_topic": true }, { "descriptor": "Human Umbilical Vein Endothelial Cells", "descriptor_ui": "D061307", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Intercellular Junctions", "descriptor_ui": "D007365", "major_topic": false }, { "descriptor": "KRIT1 Protein", "descriptor_ui": "D000075927", "major_topic": true }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false } ], "publication": { "conference_name": null, "date": "2025 Dec 27", "date_precision": "day", "issue": "", "normalized_date": "2025-12-27", "pages": "", "proceedings_title": null, "publisher": "", "title": "Nature communications", "volume": "", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Circumferential actomyosin bundles anchored by CCM1 drive endothelial cell contraction and vessel constriction.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Skeletal muscle atrophy underlies sarcopenia, frailty, and muscular dystrophies, but the molecular mechanisms linking oxidative stress to muscle degeneration remain incompletely understood. We previously identified protein complex formation between transient receptor potential canonical 3 (TRPC3) and NADPH oxidase 2 (Nox2) as a key driver of anthracycline-induced myocardial atrophy. Here, we investigated whether this complex also contributes to skeletal muscle wasting. In skeletal muscle from sciatic nerve transection model mice and Duchenne muscular dystrophy (mdx) mice, TRPC3-Nox2 complex formation was enhanced. TRPC3 deletion significantly attenuated denervation-induced soleus atrophy and reduced reactive oxygen species (ROS) production. TRPC3-Nox2 complex formation was upregulated in the soleus muscle (SM) of mdx mice. Pharmacological disruption of the TRPC3-Nox2 interaction improved muscle size and strength and reduced plasma creatine kinase in mdx mice. A recombinant adeno-associated virus (AAV) encoding a TRPC3 C-terminal peptide was used to suppress TRPC3-Nox2 complex formation in vivo. AAV-mediated expression of TRPC3 C-terminal peptide mitigated muscle wasting (CSA) in mdx mice, while muscle strength and plasma CK were not significantly improved. Thus, TRPC3-Nox2 complex formation may be a pivotal driver of oxidative stress-mediated skeletal muscle atrophy. Targeting this protein-protein interaction represents a promising therapeutic strategy for Duchenne muscular dystrophy (DMD) and other intractable muscle-wasting disorders.", "classifications": [ { "id": "JPMJCR2024", "label": "JPMJCR2024", "researcher": "Motohiro Nishida", "type": "grant" }, { "id": "Nishida", "label": "Group Nishida", "parent": "Nishida", "type": "group" }, { "id": "Nishimura", "label": "Group Nishimura", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yuri", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Di", "last_name": "Wu", "name": null }, { "creator_type": "author", "first_name": "Tomoya", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Yara", "last_name": "Atef", "name": null }, { "creator_type": "author", "first_name": "Koichi", "last_name": "Ayukawa", "name": null }, { "creator_type": "author", "first_name": "Xinya", "last_name": "Mi", "name": null }, { "creator_type": "author", "first_name": "Kazuhiro", "last_name": "Nishiyama", "name": null }, { "creator_type": "author", "first_name": "Akiyuki", "last_name": "Nishimura", "name": null }, { "creator_type": "author", "first_name": "Motohiro", "last_name": "Nishida", "name": null } ], "identifiers": { "doi": { "normalized": "10.3390/antiox15010038" }, "pmcid": { "normalized": "PMC12838269" }, "pmid": { "normalized": "41596097" } }, "mesh": [], "publication": { "conference_name": null, "date": "2025 Dec 26", "date_precision": "day", "issue": "1", "normalized_date": "2025-12-26", "pages": "", "proceedings_title": null, "publisher": "", "title": "Antioxidants (Basel, Switzerland)", "volume": "15", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Inhibition of TRPC3-Nox2 Complex Formation Ameliorates Skeletal Muscle Atrophy.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Infrared thermal cameras can noninvasively measure the surface temperatures of objects and are widely used as fever-screening systems for infectious diseases. However, body temperature measurements alone are often insufficient for identifying people with infections. To address the inherent limitations of fever-based screening, this study aimed to develop analytical methods that enable multi-vital sensing alongside body temperature measurement using a single mid-wave infrared (MWIR) camera. Respiratory parameters were assessed by visualizing exhaled airflow based on MWIR absorption by carbon dioxide, whereas the heart rate was estimated from subtle temperature fluctuations captured using high thermal resolution. The experimental results validated the proposed method, showing that the developed system achieved good agreement with reference measurements; the respiratory rate, heart rate, and body temperature showed strong correlations (r = 0.864-0.987) and acceptable limits of agreement in Bland-Altman analyses. The exhalation volume was quantified from the visualized airflow and was found to align with the expected physiological ranges. These results demonstrate that noncontact multi-vital sensing can be achieved using a single MWIR camera, without the need for complex instrumentation. The proposed method holds promise for high-precision infection screening, remote health monitoring, and in-home physiological assessment.", "classifications": [ { "id": "Suzuki", "label": "Group Suzuki", "parent": "Takekawa", "type": "group" }, { "id": "Takekawa", "label": "Team Takekawa", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Tomohiko", "last_name": "Akiyama", "name": null }, { "creator_type": "author", "first_name": "Kei-Ichiro", "last_name": "Ishiguro", "name": null }, { "creator_type": "author", "first_name": "Nana", "last_name": "Chikazawa", "name": null }, { "creator_type": "author", "first_name": "Shigeru B. H.", "last_name": "Ko", "name": null }, { "creator_type": "author", "first_name": "Masashi", "last_name": "Yukawa", "name": null }, { "creator_type": "author", "first_name": "Minoru S. H.", "last_name": "Ko", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Suzuki", "name": null } ], "identifiers": { "doi": { "normalized": "10.3390/s26010098" }, "pmcid": { "normalized": "PMC12787706" }, "pmid": { "normalized": "41516532" } }, "mesh": [ { "descriptor": "Body Temperature", "descriptor_ui": "D001831", "major_topic": false }, { "descriptor": "Carbon Dioxide", "descriptor_ui": "D002245", "major_topic": false }, { "descriptor": "Heart Rate", "descriptor_ui": "D006339", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Infrared Rays", "descriptor_ui": "D007259", "major_topic": false }, { "descriptor": "Monitoring, Physiologic", "descriptor_ui": "D008991", "major_topic": false }, { "descriptor": "Respiration", "descriptor_ui": "D012119", "major_topic": true }, { "descriptor": "Respiratory Rate", "descriptor_ui": "D056152", "major_topic": false }, { "descriptor": "Thermography", "descriptor_ui": "D013817", "major_topic": true }, { "descriptor": "Vital Signs", "descriptor_ui": "D055986", "major_topic": true } ], "publication": { "conference_name": null, "date": "2025 Dec 23", "date_precision": "day", "issue": "1", "normalized_date": "2025-12-23", "pages": "", "proceedings_title": null, "publisher": "", "title": "Sensors (Basel, Switzerland)", "volume": "26", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Noncontact Visualization of Respiration and Vital Sign Monitoring Using a Single Mid-Wave Infrared Thermal Camera: Preliminary Proof-of-Concept.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "", "classifications": [ { "id": "Fujiwara", "label": "Group Fujiwara", "parent": "Fujiwara", "type": "group" }, { "id": "Fujiwara", "label": "Team Fujiwara", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Michael", "last_name": "Spantios", "name": null }, { "creator_type": "author", "first_name": "Tsukasa", "last_name": "Ueno", "name": null }, { "creator_type": "author", "first_name": "Mami", "last_name": "Shibata", "name": null }, { "creator_type": "author", "first_name": "Naoya", "last_name": "Oishi", "name": null }, { "creator_type": "author", "first_name": "Morio", "last_name": "Aki", "name": null }, { "creator_type": "author", "first_name": "Toshiya", "last_name": "Murai", "name": null }, { "creator_type": "author", "first_name": "Hironobu", "last_name": "Fujiwara", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41598-025-32786-1" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "41423552" } }, "mesh": [ { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Brain", "descriptor_ui": "D001921", "major_topic": true }, { "descriptor": "Brain Mapping", "descriptor_ui": "D001931", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Magnetic Resonance Imaging", "descriptor_ui": "D008279", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Martial Arts", "descriptor_ui": "D016139", "major_topic": true }, { "descriptor": "Mindfulness", "descriptor_ui": "D064866", "major_topic": true }, { "descriptor": "Nerve Net", "descriptor_ui": "D009415", "major_topic": true }, { "descriptor": "Reaction Time", "descriptor_ui": "D011930", "major_topic": false }, { "descriptor": "Young Adult", "descriptor_ui": "D055815", "major_topic": false } ], "publication": { "conference_name": null, "date": "2025 Dec 21", "date_precision": "day", "issue": "", "normalized_date": "2025-12-21", "pages": "", "proceedings_title": null, "publisher": "", "title": "Scientific reports", "volume": "", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "The development of mindfulness in martial art kendo players: AfMRI analysis of the triple network.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Mpox virus (MPXV) infection exhibits different case fatality rates and symptoms depending on its clade. However, there has been insufficient molecular biological analysis of the differences between clades. Here, we investigated whether clades can be distinguished by focusing on the expression of MPXV genes. The replication efficiency of MPXV clade IIb, responsible for the 2022 mpox outbreak, was lower than that of clades Ia and IIa. We found that OPG175 was highly expressed in MPXV clade IIb-infected cells. Suppression of OPG175 expression significantly increased the infectious titer of MPXV, whereas OPG175 overexpression significantly decreased it. We also found that OPG175 overexpression enhanced the expression of Wnt signaling-related genes, and activation of Wnt signaling decreased MPXV replication efficiency. Therefore, high OPG175 expression in MPXV clade IIb-infected cells likely inhibits MPXV replication via activation of Wnt signaling.", "classifications": [ { "id": "Yamamoto", "label": "Group Yamamoto", "parent": "Toyoshima", "type": "group" }, { "id": "Toyoshima", "label": "Team Toyoshima", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yoshitaka", "last_name": "Nakata", "name": null }, { "creator_type": "author", "first_name": "Masako", "last_name": "Yamasaki", "name": null }, { "creator_type": "author", "first_name": "Yukio", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Keiya", "last_name": "Uriu", "name": null }, { "creator_type": "author", "first_name": "Rina", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Kei", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Akatsuki", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Kazuo", "last_name": "Takayama", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.isci.2025.114105" }, "pmcid": { "normalized": "PMC12756559" }, "pmid": { "normalized": "41488350" } }, "mesh": [], "publication": { "conference_name": null, "date": "2025 Dec 19", "date_precision": "day", "issue": "12", "normalized_date": "2025-12-19", "pages": "114105", "proceedings_title": null, "publisher": "", "title": "iScience", "volume": "28", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Mpox virus OPG175 negatively regulates viral replication by controlling Wnt signaling.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Raman spectroscopy enables label-free and non-destructive structural analysis of biomolecules; however, its application is limited by the inherently weak Raman signals, which necessitate high concentrations of biomolecules for detection. In our previous study, we developed a liquid-liquid phase separation (LLPS)-assisted Raman method, in which biomacromolecules are concentrated into PEG-induced droplets, enabling the acquisition of high signal-to-noise (S/N) Raman spectra from dilute solutions with small volumes, such as 30 muM and 50 muL. We demonstrate here its broad analytical utility for several applications, including real-time monitoring of catalytic reactions such as RNA degradation and quantitative detection of protein-small molecule interactions exemplified by the avidin-biotin system. Furthermore, small molecules such as amino acids, monosaccharides and supersulfides were successfully concentrated, allowing their Raman spectra to be obtained with markedly improved S/N ratios. This technique thus provides a simple, highly sensitive and versatile analytical platform for Raman-based biochemical studies, with wide potential applications in analyzing biomolecular structures and intermolecular interactions, as well as diagnostics.", "classifications": [ { "id": "JPMJCR2024", "label": "JPMJCR2024", "researcher": "Motohiro Nishida", "type": "grant" }, { "id": "Nakabayashi", "label": "Group Nakabayashi", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Group Nishida", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Lisa", "last_name": "Kageyama", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Tahara", "name": null }, { "creator_type": "author", "first_name": "Reona", "last_name": "Tobita", "name": null }, { "creator_type": "author", "first_name": "Shinji", "last_name": "Kajimoto", "name": null }, { "creator_type": "author", "first_name": "Takakazu", "last_name": "Nakabayashi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1039/d5an00973a" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "41404870" } }, "mesh": [ { "descriptor": "Amino Acids", "descriptor_ui": "D000596", "major_topic": false }, { "descriptor": "Avidin", "descriptor_ui": "D001360", "major_topic": false }, { "descriptor": "Biotin", "descriptor_ui": "D001710", "major_topic": false }, { "descriptor": "Microscopy", "descriptor_ui": "D008853", "major_topic": true }, { "descriptor": "Phase Separation", "descriptor_ui": "D000095496", "major_topic": false }, { "descriptor": "Polyethylene Glycols", "descriptor_ui": "D011092", "major_topic": false }, { "descriptor": "Proteins", "descriptor_ui": "D011506", "major_topic": true }, { "descriptor": "Spectrum Analysis, Raman", "descriptor_ui": "D013059", "major_topic": true } ], "publication": { "conference_name": null, "date": "2025 Dec 17", "date_precision": "day", "issue": "", "normalized_date": "2025-12-17", "pages": "", "proceedings_title": null, "publisher": "", "title": "The Analyst", "volume": "", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Liquid-liquid phase separation-assisted Raman microscopy for sensitive and label-free analysis of enzymatic reactions and protein-small molecule interactions.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "INTRODUCTION: Busulfan (BU)- and thiotepa (TT)-containing regimens have been approved for autologous stem cell transplantation (ASCT) in central nervous system lymphoma (CNSL). However, optimal doses of these regimens remain unclear. This study retrospectively analyzed the efficacy and toxicity of the Bu2TT regimen. METHOD: The study included 12 patients with CNSL who received Bu2TT (BU 3.2 mg/kg, days - 7 and - 6; TT 5 mg/kg, days - 5 and - 4) followed by ASCT at our institution after April 2020. RESULTS: Four patients were newly diagnosed (primary 3; secondary 1), and eight relapsed (primary 6; secondary 2). The median age was 62 years. Nine patients received high-dose MTX-based regimens as pre-transplant therapy. The other three received tirabrutinib, which was combined with localized radiotherapy (CyberKnife) in one patient. Disease status before ASCT was complete remission (CR) in 7 patients and partial remission in 5. Complications included febrile neutropenia (10/12 patients) and grade 3 anorexia (5/12 patients). Disease status after transplantation was CR in 10 patients and progressive disease in 2. OS and PFS rates at 2 years were 100% and 71%, respectively. CONCLUSION: Our data suggest that Bu2TT had acceptable safety and efficacy. These results provide a rationale for further analyses in prospective multi-institutional trials.", "classifications": [ { "id": "Nishikii", "label": "Group Nishikii", "parent": "Shintaku", "type": "group" }, { "id": "Shintaku", "label": "Team Shintaku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Keiichiro", "last_name": "Hattori", "name": null }, { "creator_type": "author", "first_name": "Naoki", "last_name": "Kurita", "name": null }, { "creator_type": "author", "first_name": "Fumiaki", "last_name": "Matsumura", "name": null }, { "creator_type": "author", "first_name": "Kenichi", "last_name": "Makishima", "name": null }, { "creator_type": "author", "first_name": "Sakurako", "last_name": "Suma", "name": null }, { "creator_type": "author", "first_name": "Yuya", "last_name": "Sasaki", "name": null }, { "creator_type": "author", "first_name": "Yasuhito", "last_name": "Suehara", "name": null }, { "creator_type": "author", "first_name": "Yumiko", "last_name": "Maruyama", "name": null }, { "creator_type": "author", "first_name": "Tatsuhiro", "last_name": "Sakamoto", "name": null }, { "creator_type": "author", "first_name": "Takayasu", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Hidekazu", "last_name": "Nishikii", "name": null }, { "creator_type": "author", "first_name": "Narushi", "last_name": "Sugii", "name": null }, { "creator_type": "author", "first_name": "Masahide", "last_name": "Matsuda", "name": null }, { "creator_type": "author", "first_name": "Eiichi", "last_name": "Ishikawa", "name": null }, { "creator_type": "author", "first_name": "Naoshi", "last_name": "Obara", "name": null }, { "creator_type": "author", "first_name": "Mamiko", "last_name": "Sakata-Yanagimoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/s12185-025-04130-w" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "41400781" } }, "mesh": [ { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Antineoplastic Combined Chemotherapy Protocols", "descriptor_ui": "D000971", "major_topic": true }, { "descriptor": "Busulfan", "descriptor_ui": "D002066", "major_topic": true }, { "descriptor": "Central Nervous System Neoplasms", "descriptor_ui": "D016543", "major_topic": true }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Hematopoietic Stem Cell Transplantation", "descriptor_ui": "D018380", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Lymphoma", "descriptor_ui": "D008223", "major_topic": true }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Retrospective Studies", "descriptor_ui": "D012189", "major_topic": false }, { "descriptor": "Thiotepa", "descriptor_ui": "D013852", "major_topic": true }, { "descriptor": "Transplantation Conditioning", "descriptor_ui": "D019172", "major_topic": true }, { "descriptor": "Transplantation, Autologous", "descriptor_ui": "D014182", "major_topic": false }, { "descriptor": "Treatment Outcome", "descriptor_ui": "D016896", "major_topic": false } ], "publication": { "conference_name": null, "date": "2025 Dec 16", "date_precision": "day", "issue": "", "normalized_date": "2025-12-16", "pages": "", "proceedings_title": null, "publisher": "", "title": "International journal of hematology", "volume": "", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "A retrospective analysis of autologous stem cell transplantation conditioning with reduced-dose busulfan/thiotepa for patients with central nervous system lymphomas at a single institution.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: Uterine leiomyosarcoma (uLMS) has a poor prognosis owing to its resistance to chemotherapy. Therefore, novel therapeutic targets for uLMS should be identified. Suppressor license of variegation 3-9 homolog 2 (SUV39H2) is a histone methyltransferase that promotes the repair of double-strand DNA breaks by recruiting phosphorylated H2AX (gammaH2AX). In this study, we investigated the potential therapeutic targets of SUV39H2 in uLMS and the mechanism of synthetic lethality between PARP inhibitors and the SUV39H2 inhibitor OTS186935. METHODS: First, we analyzed the mRNA and protein expression of SUV39H2 in the clinical tissues of uLMS, normal myometrium, and leiomyomas using real-time polymerase chain reaction and immunohistochemistry, respectively. Next, we conducted drug sensitivity assays for OTS186935 alone and in combination with olaparib, a poly (ADP-ribose) polymerase inhibitor, using the uLMS cell lines SK-LMS-1 and SK-UT-1. We performed western blotting, immunofluorescence, and chromatin immunoprecipitation sequencing (ChIP-seq) to investigate gammaH2AX following OTS186935 treatment in addition to in vivo experiments using nude mice with subcutaneously implanted uLMS. RESULTS: SUV39H2 expression in uLMS was significantly higher than that in the normal myometrium and leiomyomas. OTS186935 decreased the viability of both cell lines, and its combination with olaparib resulted in synthetic lethality in SK-UT-1 cells (combination index = 0.88). After treatment with OTS186935, gammaH2AX accumulation decreased. ChIP-seq also showed downregulation of gammaH2AX following OTS186935 treatment. Notably, the combination of OTS186935 and a PARP inhibitor was significantly more effective in vivo. CONCLUSION: OTS186935 inhibited double-strand DNA break repair, as evidenced by gammaH2AX downregulation by ChIP-seq and other assays. Combining OTS186935 with olaparib demonstrated activity resembling synthetic lethality; however, further validation is required before clinical translation.", "classifications": [ { "id": "Hamamoto", "label": "Group Hamamoto", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yusuke", "last_name": "Toyohara", "name": null }, { "creator_type": "author", "first_name": "Kenbun", "last_name": "Sone", "name": null }, { "creator_type": "author", "first_name": "Kohei", "last_name": "Kumegawa", "name": null }, { "creator_type": "author", "first_name": "Yoko", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Ryuta", "last_name": "Hachijo", "name": null }, { "creator_type": "author", "first_name": "Asako", "last_name": "Kukita", "name": null }, { "creator_type": "author", "first_name": "Ayumi", "last_name": "Taguchi", "name": null }, { "creator_type": "author", "first_name": "Masako", "last_name": "Ikemura", "name": null }, { "creator_type": "author", "first_name": "Yuichiro", "last_name": "Miyamoto", "name": null }, { "creator_type": "author", "first_name": "Michihiro", "last_name": "Tanikawa", "name": null }, { "creator_type": "author", "first_name": "Takayuki", "last_name": "Iriyama", "name": null }, { "creator_type": "author", "first_name": "Mayuyo", "last_name": "Mori", "name": null }, { "creator_type": "author", "first_name": "Ryuji", "last_name": "Hamamoto", "name": null }, { "creator_type": "author", "first_name": "Tetsuo", "last_name": "Ushiku", "name": null }, { "creator_type": "author", "first_name": "Katsuhiko", "last_name": "Oda", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Hirota", "name": null }, { "creator_type": "author", "first_name": "Reo", "last_name": "Maruyama", "name": null }, { "creator_type": "author", "first_name": "Yutaka", "last_name": "Osuga", "name": null } ], "identifiers": { "doi": { "normalized": "10.1186/s12885-025-15267-6" }, "pmcid": { "normalized": "PMC12709732" }, "pmid": { "normalized": "41402789" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Antineoplastic Combined Chemotherapy Protocols", "descriptor_ui": "D000971", "major_topic": true }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "DNA Breaks, Double-Stranded", "descriptor_ui": "D053903", "major_topic": false }, { "descriptor": "DNA Repair", "descriptor_ui": "D004260", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Histone-Lysine N-Methyltransferase", "descriptor_ui": "D011495", "major_topic": true }, { "descriptor": "Histones", "descriptor_ui": "D006657", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Leiomyosarcoma", "descriptor_ui": "D007890", "major_topic": true }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Nude", "descriptor_ui": "D008819", "major_topic": false }, { "descriptor": "Myometrium", "descriptor_ui": "D009215", "major_topic": false }, { "descriptor": "Phthalazines", "descriptor_ui": "D010793", "major_topic": false }, { "descriptor": "Piperazines", "descriptor_ui": "D010879", "major_topic": false }, { "descriptor": "Poly(ADP-ribose) Polymerase Inhibitors", "descriptor_ui": "D000067856", "major_topic": true }, { "descriptor": "Synthetic Lethal Mutations", "descriptor_ui": "D000072020", "major_topic": true }, { "descriptor": "Uterine Neoplasms", "descriptor_ui": "D014594", "major_topic": true }, { "descriptor": "Xenograft Model Antitumor Assays", "descriptor_ui": "D023041", "major_topic": false } ], "publication": { "conference_name": null, "date": "2025 Dec 16", "date_precision": "day", "issue": "1", "normalized_date": "2025-12-16", "pages": "1873", "proceedings_title": null, "publisher": "", "title": "BMC cancer", "volume": "25", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Synthetic lethality from the combination of a histone methyltransferase SUV39H2 inhibitor and a poly (ADP-ribose) polymerase inhibitor for uterine leiomyosarcoma.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Single-cell sequencing has advanced our understanding of cell-type diversity and heterogeneity. However, existing single-cell multi-omics methods lack the ability to monitor gene expression dynamics during S-phase progression. Here, we introduce single-cell (sc)Repli-RamDA-seq (scRR-seq), a multi-omics method that enables high-resolution DNA replication profiling and full-length total RNA sequencing from the same single cell in a haplotype-specific manner. scRR-seq generates DNA replication and RNA sequencing data comparable to individually obtained scRepli-seq and scRamDA-seq data, respectively. Unlike other scDNA/RNA-seq methods, scRR-seq allows one to tell the S-phase stage of a given cell based on the percentage of the replicated genome derived from scRepli-seq data. This facilitates analysis of gene expression dynamics during S-phase progression, enabling the identification of S-phase progression markers. scRR-seq also detects copy-number variation in non-S-phase cells and outperforms other scDNA/RNA-seq methods in various measures. Taken together, scRR-seq is a robust single-cell multi-omics method with promising potential for comprehensive genome/transcriptome analysis.", "classifications": [ { "id": "JPMJCR1926", "label": "JPMJCR1926", "researcher": "Hironobu Fujiwara", "type": "grant" }, { "id": "Fujiwara", "label": "Group Fujiwara", "parent": "Fujiwara", "type": "group" }, { "id": "Nikaido", "label": "Group Nikaido", "parent": "Fujiwara", "type": "group" }, { "id": "Fujiwara", "label": "Team Fujiwara", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Rawin", "last_name": "Poonperm", "name": null }, { "creator_type": "author", "first_name": "Taiki", "last_name": "Yoneda", "name": null }, { "creator_type": "author", "first_name": "Taito", "last_name": "Imada", "name": null }, { "creator_type": "author", "first_name": "Saori", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Takako", "last_name": "Ichinose", "name": null }, { "creator_type": "author", "first_name": "Hisashi", "last_name": "Miura", "name": null }, { "creator_type": "author", "first_name": "Tetsutaro", "last_name": "Hayashi", "name": null }, { "creator_type": "author", "first_name": "Mariko", "last_name": "Kuse", "name": null }, { "creator_type": "author", "first_name": "Mika", "last_name": "Yoshimura", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Nagao", "name": null }, { "creator_type": "author", "first_name": "Chikashi", "last_name": "Obuse", "name": null }, { "creator_type": "author", "first_name": "Itoshi", "last_name": "Nikaido", "name": null }, { "creator_type": "author", "first_name": "Ichiro", "last_name": "Hiratani", "name": null }, { "creator_type": "author", "first_name": "Shin-Ichiro", "last_name": "Takebayashi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41467-025-64688-1" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "41397953" } }, "mesh": [ { "descriptor": "DNA Copy Number Variations", "descriptor_ui": "D056915", "major_topic": false }, { "descriptor": "DNA Replication", "descriptor_ui": "D004261", "major_topic": false }, { "descriptor": "Gene Expression Profiling", "descriptor_ui": "D020869", "major_topic": true }, { "descriptor": "High-Throughput Nucleotide Sequencing", "descriptor_ui": "D059014", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Multiomics", "descriptor_ui": "D000095028", "major_topic": false }, { "descriptor": "RNA-Seq", "descriptor_ui": "D000081246", "major_topic": false }, { "descriptor": "S Phase", "descriptor_ui": "D016196", "major_topic": true }, { "descriptor": "Sequence Analysis, RNA", "descriptor_ui": "D017423", "major_topic": false }, { "descriptor": "Single-Cell Analysis", "descriptor_ui": "D059010", "major_topic": true } ], "publication": { "conference_name": null, "date": "2025 Dec 15", "date_precision": "day", "issue": "1", "normalized_date": "2025-12-15", "pages": "10902", "proceedings_title": null, "publisher": "", "title": "Nature communications", "volume": "16", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "scRepli-RamDA-seq: a multi-omics technology enabling the analysis of gene expression dynamics during S-phase.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Cellular senescence is deeply involved in physiological homeostasis, development, tissue repair, aging, and diseases. Senescent cells (SnCs) accumulate in aged tissues and exert deleterious effects by secreting proinflammatory molecules that contribute to chronic inflammation and aging-related diseases. We revealed that an aberrant interaction between glycolytic PGAM1 and Chk1 kinase is augmented in SnCs associated with increased glycolysis, whose byproduct, lactate, promotes this binding in a noncell autonomous manner. The pseudo-Warburg effect of SnCs with enhanced PPP (pentose phosphate pathway) activity is maintained by HIF-2alpha phosphorylation by Chk1 and subsequent upregulation of glycolytic enzymes, creating a vicious cycle reprogramming the glycolytic pathway in SnCs. HIF-2alpha also activates FoxM1 expression, which transcriptionally suppresses proapoptotic profiles, including BIM, and upregulates DNA repair machineries in SnCs. FoxM1 thus supports the genomic integrity and survival capacity of SnCs during their glycolytic changes. Chemical abrogation of PGAM1-Chk1 binding reverts these phenotypes and eliminates SnCs through senolysis. Inhibition of the PGAM1-Chk1 interaction improves physiological parameters during aging and inhibits lung fibrosis in mouse models. Our study highlights a novel pathway contributing to the metabolic reprogramming of SnCs and how the use of a new senolytic molecule that targets the PGAM-Chk1 interaction creates a specific vulnerability of those cells to potentially fight age-related diseases.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Takumi", "last_name": "Mikawa", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Kameda", "name": null }, { "creator_type": "author", "first_name": "Sumiko", "last_name": "Ikari", "name": null }, { "creator_type": "author", "first_name": "Eri", "last_name": "Shibata", "name": null }, { "creator_type": "author", "first_name": "Shuyu", "last_name": "Liu", "name": null }, { "creator_type": "author", "first_name": "Sawa", "last_name": "Miyagawa", "name": null }, { "creator_type": "author", "first_name": "Koh", "last_name": "Ono", "name": null }, { "creator_type": "author", "first_name": "Tomiko", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Akihiko", "last_name": "Yoshizawa", "name": null }, { "creator_type": "author", "first_name": "Masataka", "last_name": "Sugimoto", "name": null }, { "creator_type": "author", "first_name": "Shuichi", "last_name": "Shibuya", "name": null }, { "creator_type": "author", "first_name": "Takahiko", "last_name": "Shimizu", "name": null }, { "creator_type": "author", "first_name": "Julio", "last_name": "Almunia", "name": null }, { "creator_type": "author", "first_name": "Noboru", "last_name": "Ogiso", "name": null }, { "creator_type": "author", "first_name": "Gwladys", "last_name": "Revechon", "name": null }, { "creator_type": "author", "first_name": "Alberta", "last_name": "Palazzo", "name": null }, { "creator_type": "author", "first_name": "David", "last_name": "Bernard", "name": null }, { "creator_type": "author", "first_name": "Hiroaki", "last_name": "Kanda", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Keiyo", "last_name": "Takubo", "name": null }, { "creator_type": "author", "first_name": "Shin", "last_name": "Morioka", "name": null }, { "creator_type": "author", "first_name": "Junko", "last_name": "Sasaki", "name": null }, { "creator_type": "author", "first_name": "Takehiko", "last_name": "Sasaki", "name": null }, { "creator_type": "author", "first_name": "Akihiro", "last_name": "Itamoto", "name": null }, { "creator_type": "author", "first_name": "Takayuki", "last_name": "Fujii", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Seno", "name": null }, { "creator_type": "author", "first_name": "Nobuya", "last_name": "Inagaki", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Kondoh", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41392-025-02502-6" }, "pmcid": { "normalized": "PMC12702999" }, "pmid": { "normalized": "41392167" } }, "mesh": [ { "descriptor": "Aging", "descriptor_ui": "D000375", "major_topic": true }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Basic Helix-Loop-Helix Proteins", "descriptor_ui": "D051792", "major_topic": false }, { "descriptor": "Cellular Senescence", "descriptor_ui": "D016922", "major_topic": true }, { "descriptor": "Checkpoint Kinase 1", "descriptor_ui": "D000071877", "major_topic": true }, { "descriptor": "Forkhead Box Protein M1", "descriptor_ui": "D000072278", "major_topic": true }, { "descriptor": "Glycolysis", "descriptor_ui": "D006019", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false } ], "publication": { "conference_name": null, "date": "2025 Dec 15", "date_precision": "day", "issue": "1", "normalized_date": "2025-12-15", "pages": "402", "proceedings_title": null, "publisher": "", "title": "Signal transduction and targeted therapy", "volume": "10", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Abrogation of aberrant glycolytic interactions eliminates senescent cells and alleviates aging-related dysfunctions.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "CONTEXT: Previous metabolomics studies suggest potential associations between menopausal changes in lipids and an increased risk of metabolic syndrome (MetS). However, longitudinal data on other key metabolites, such as branched-chain amino acids and homocysteine, remain limited, and most studies lack long-term follow-up across the menopause transition. OBJECTIVE: This study aimed to investigate longitudinal changes in circulating metabolites during menopause over a mean follow-up of 5 years and assess their associations with subsequent MetS development. METHODS: Premenopausal women from the Tsuruoka Metabolomics Cohort Study who participated in at least one follow-up survey were included. Menopausal status, data on MetS, and plasma metabolites profiled using capillary electrophoresis mass spectrometry were assessed at each visit. Thirty-one metabolites were examined for associations with menopausal status using mixed-effects models. The association of these menopause-related metabolites with MetS development was examined via logistic regression analysis adjusted for follow-up duration. RESULTS: Among 953 women (43.8 +/- 5.4 years old), 316 (33.2%) reached menopause during follow-up (5.0 +/- 1.1 years). Eighteen metabolites changed significantly with menopause, particularly those related to BCAA metabolism, urea cycle, and homocysteine metabolism. Of 695 women without MetS at baseline, 65 (9.4%) developed MetS. Glutamate (odds ratio [95% confidence interval]: 1.95 [1.49-2.57]) was associated with higher MetS risk. Higher levels of glutamate, valine, leucine, and cystine were significantly associated with the development of hyperglycemia. CONCLUSIONS: Longitudinal changes in charged metabolites occur across the menopausal transition, with specific metabolites such as glutamate possibly contributing to the metabolic alterations underlying increased MetS risk.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Atsuko", "last_name": "Miyake", "name": null }, { "creator_type": "author", "first_name": "Miho", "last_name": "Iida", "name": null }, { "creator_type": "author", "first_name": "Sei", "last_name": "Harada", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Sugiyama", "name": null }, { "creator_type": "author", "first_name": "Minako", "last_name": "Matsumoto", "name": null }, { "creator_type": "author", "first_name": "Naoko", "last_name": "Miyagawa", "name": null }, { "creator_type": "author", "first_name": "Ryota", "last_name": "Toki", "name": null }, { "creator_type": "author", "first_name": "Shun", "last_name": "Edagawa", "name": null }, { "creator_type": "author", "first_name": "Aya", "last_name": "Hirata", "name": null }, { "creator_type": "author", "first_name": "Kazuyo", "last_name": "Kuwabara", "name": null }, { "creator_type": "author", "first_name": "Tomonori", "last_name": "Okamura", "name": null }, { "creator_type": "author", "first_name": "Asako", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Kaori", "last_name": "Amano", "name": null }, { "creator_type": "author", "first_name": "Akiyoshi", "last_name": "Hirayama", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Sugimoto", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Masaru", "last_name": "Tomita", "name": null }, { "creator_type": "author", "first_name": "Kazuharu", "last_name": "Arakawa", "name": null }, { "creator_type": "author", "first_name": "Iori", "last_name": "Kisu", "name": null }, { "creator_type": "author", "first_name": "Wataru", "last_name": "Yamagami", "name": null }, { "creator_type": "author", "first_name": "Toru", "last_name": "Takebayashi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1210/clinem/dgaf666" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "41389027" } }, "mesh": [ { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Amino Acids, Branched-Chain", "descriptor_ui": "D000597", "major_topic": false }, { "descriptor": "Biomarkers", "descriptor_ui": "D015415", "major_topic": true }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Follow-Up Studies", "descriptor_ui": "D005500", "major_topic": false }, { "descriptor": "Homocysteine", "descriptor_ui": "D006710", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Longitudinal Studies", "descriptor_ui": "D008137", "major_topic": false }, { "descriptor": "Menopause", "descriptor_ui": "D008593", "major_topic": true }, { "descriptor": "Metabolic Syndrome", "descriptor_ui": "D024821", "major_topic": true }, { "descriptor": "Metabolome", "descriptor_ui": "D055442", "major_topic": false }, { "descriptor": "Metabolomics", "descriptor_ui": "D055432", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Risk Factors", "descriptor_ui": "D012307", "major_topic": false } ], "publication": { "conference_name": null, "date": "2025 Dec 13", "date_precision": "day", "issue": "", "normalized_date": "2025-12-13", "pages": "dgaf666", "proceedings_title": null, "publisher": "", "title": "The Journal of clinical endocrinology and metabolism", "volume": "", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Longitudinal study of plasma metabolites during menopause and their associations with later onset of metabolic syndrome.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Despite the high design freedom of metal-organic frameworks (MOFs), flexible ligands that bear sp(3)-hybridized carbon atoms in their core are generally avoided as building blocks for MOFs because they may compromise framework stability. Herein, a 2D MOF (CBoard) is reported incorporating a dibenzocyclooctadiene with a flexible medium-sized ring at the core as a flexible ligand. The moderate flexibility of the incorporated dibenzocyclooctadiene in CBoard reduces the strain induced by external stimuli on the coordination bonds, conferring cyclic stability upon guest adsorption-desorption. Furthermore, the sp(3)-hybridized carbon-rich nanospace endows CBoard with water resistance and surface hydrophobicity. This hydrophobic nanospace preferentially captures ethanol over water, highlighting its potential for applications in ethanol-water separation in dilute aqueous solutions.", "classifications": [ { "id": "Hijikata", "label": "Group Hijikata", "parent": "Tsuchiya", "type": "group" }, { "id": "Tsuchiya", "label": "Team Tsuchiya", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Junichi", "last_name": "Usuba", "name": null }, { "creator_type": "author", "first_name": "Yuh", "last_name": "Hijikata", "name": null }, { "creator_type": "author", "first_name": "Teppei", "last_name": "Takahara", "name": null }, { "creator_type": "author", "first_name": "Shinpei", "last_name": "Kusaka", "name": null }, { "creator_type": "author", "first_name": "Ryotaro", "last_name": "Matsuda", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/smll.202512697" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "41388577" } }, "mesh": [], "publication": { "conference_name": null, "date": "2025 Dec 12", "date_precision": "day", "issue": "", "normalized_date": "2025-12-12", "pages": "e12697", "proceedings_title": null, "publisher": "", "title": "Small (Weinheim an der Bergstrasse, Germany)", "volume": "", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "A Durable Metal-Organic Framework with a Hydrophobic sp(3)-Carbon-Rich Nanospace Constructed from Flexible Medium-Sized Ring Ligands.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The transition to parenthood brings significant changes in behavior toward offspring. For instance, in anticipation of their offspring, male mice shift from infanticidal to caregiving behaviors. While the release of oxytocin from the paraventricular hypothalamus (PVH) plays a critical role in paternal caregiving, it does not fully account for the entire behavioral shift. The specific downstream neurons and signaling mechanisms involved in this process remain obscure. Here, we demonstrate that PVH vasopressin neurons also essentially contribute to a paternal behavioral shift. This vasopressin signal is partially transmitted through oxytocin receptors (OTRs) expressed in the anterior commissure and medial nuclei of the preoptic area. These OTR-expressing neurons receive inputs from both PVH oxytocin and vasopressin neurons and are responsible for expressing paternal caregiving behaviors. Collectively, this non-canonical vasopressin-to-OTR crosstalk within specific limbic circuits acts as a pivotal regulator of paternal behavioral changes in mice.", "classifications": [ { "id": "Miyamichi", "label": "Group Miyamichi", "parent": "Enomoto", "type": "group" }, { "id": "Enomoto", "label": "Team Enomoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Kengo", "last_name": "Inada", "name": null }, { "creator_type": "author", "first_name": "Mitsue", "last_name": "Hagihara", "name": null }, { "creator_type": "author", "first_name": "Kasane", "last_name": "Yaguchi", "name": null }, { "creator_type": "author", "first_name": "Satsuki", "last_name": "Irie", "name": null }, { "creator_type": "author", "first_name": "Yukiko U.", "last_name": "Inoue", "name": null }, { "creator_type": "author", "first_name": "Takayoshi", "last_name": "Inoue", "name": null }, { "creator_type": "author", "first_name": "Kazunari", "last_name": "Miyamichi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41467-025-66908-0" }, "pmcid": { "normalized": "PMC12696063" }, "pmid": { "normalized": "41372215" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Behavior, Animal", "descriptor_ui": "D001522", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Oxytocin", "descriptor_ui": "D010121", "major_topic": false }, { "descriptor": "Paraventricular Hypothalamic Nucleus", "descriptor_ui": "D010286", "major_topic": false }, { "descriptor": "Paternal Behavior", "descriptor_ui": "D010332", "major_topic": true }, { "descriptor": "Preoptic Area", "descriptor_ui": "D011301", "major_topic": true }, { "descriptor": "Receptors, Oxytocin", "descriptor_ui": "D018045", "major_topic": true }, { "descriptor": "Receptors, Vasopressin", "descriptor_ui": "D017483", "major_topic": true }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Vasopressins", "descriptor_ui": "D014667", "major_topic": true } ], "publication": { "conference_name": null, "date": "2025 Dec 10", "date_precision": "day", "issue": "1", "normalized_date": "2025-12-10", "pages": "10844", "proceedings_title": null, "publisher": "", "title": "Nature communications", "volume": "16", "year": 2025 }, "ssbd": { "database": [], "repository": [ "ssbd-repos-000449" ] }, "title": "Vasopressin-to-oxytocin receptor crosstalk in the preoptic area underlying parental behaviors in male mice.", "url": "https://www.nature.com/articles/s41467-025-66908-0", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Axial rotation (AR), a morphogenetic movement that reshapes the body axis, is widely observed in chordates, including mice and rats. AR involves complex three-dimensional deformations; however, its geometric characteristics and regulatory mechanisms remain poorly understood. Here, using the chordate Ciona robusta (Ciona intestinalis type A), we demonstrate that AR consists of two differentially regulated components-leftward bending and clockwise twisting along the anterior-posterior axis. A comparison between chorionated and dechorionated embryos revealed that dechorionation randomized the bending direction, while twisting remained consistently clockwise. Inhibition of TGF-beta signaling with SB431542 randomized both deformations. Quantitative analysis of twisting angles indicated uniform clockwise twisting along the axis, peaking during the tailbud stage and proceeding in the tail region, independent of the tip, trunk, or myofibril patterning. Although overall twisting was reduced under TGF-beta inhibition, the tail exhibited disorganized twisting. The sum of absolute twisting-angle differences in every 10 mum remained comparable to the wild type (WT). This suggests that twisting is intrinsically generated, while TGF-beta signaling aligns local twisting into a coordinated global direction. Our findings dissected the mechanisms of AR in Ciona and highlight the multilayered regulation underlying the morphogenesis of the chordate body plan and providing a foundation for understanding its biomechanical and molecular bases.", "classifications": [ { "id": "JPMJCR2123", "label": "JPMJCR2123", "researcher": "Shinya Kuroda", "type": "grant" }, { "id": "Kuroda", "label": "Group Kuroda", "parent": "Kuroda", "type": "group" }, { "id": "Okuda", "label": "Group Okuda", "parent": "Imayoshi", "type": "group" }, { "id": "Imayoshi", "label": "Team Imayoshi", "type": "team" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yuki S.", "last_name": "Kogure", "name": null }, { "creator_type": "author", "first_name": "Satoru", "last_name": "Okuda", "name": null }, { "creator_type": "author", "first_name": "Kotaro", "last_name": "Oka", "name": null }, { "creator_type": "author", "first_name": "Kohji", "last_name": "Hotta", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.ydbio.2025.12.008" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "41386418" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Benzamides", "descriptor_ui": "D001549", "major_topic": false }, { "descriptor": "Body Patterning", "descriptor_ui": "D019521", "major_topic": true }, { "descriptor": "Ciona intestinalis", "descriptor_ui": "D002938", "major_topic": true }, { "descriptor": "Dioxoles", "descriptor_ui": "D004149", "major_topic": false }, { "descriptor": "Embryo, Nonmammalian", "descriptor_ui": "D004625", "major_topic": false }, { "descriptor": "Gene Expression Regulation, Developmental", "descriptor_ui": "D018507", "major_topic": false }, { "descriptor": "Morphogenesis", "descriptor_ui": "D009024", "major_topic": true }, { "descriptor": "Rotation", "descriptor_ui": "D012399", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Transforming Growth Factor beta", "descriptor_ui": "D016212", "major_topic": false } ], "publication": { "conference_name": null, "date": "2025 Dec 10", "date_precision": "day", "issue": "", "normalized_date": "2025-12-10", "pages": "S0012-1606(25)00339-2", "proceedings_title": null, "publisher": "", "title": "Developmental biology", "volume": "", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Axial Rotation Comprises Concurrent Twisting and Bending as Distinct Morphogenetic Components in Ciona.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Numerous strategies exist to isolate hematopoietic stem cells (HSCs) using complex combinations of markers and flow cytometry. However, robust identification of HSCs using imaging techniques is substantially more challenging which has prompted the recent development of HSC reporter mice. To date, very few molecules used in these reporters have been useful for human HSC identification. Here we report that PLXDC2 is a useful marker for both mouse and human cord blood HSCs. Using a green fluorescent protein (GFP) knock-in at the Plxdc2 locus in mice (hereafter denoted as Plxdc2-GFP), we showed that Plxdc2-GFP is highly expressed in HSCs with 1 in 2.8 Plxdc2-GFP(+)CD150(+) cells giving long-term multi-lineage reconstitution in transplantation. Moreover, we developed a novel human PLXDC2 antibody and showed that human PLXDC2(+) HSCs have higher long-term multilineage reconstitution ability compared with PLXDC2(-) HSCs in a xenograft model. This study identifies PLXDC2 as a highly relevant molecule in HSC identification.", "classifications": [ { "id": "Nishikii", "label": "Group Nishikii", "parent": "Shintaku", "type": "group" }, { "id": "Shintaku", "label": "Team Shintaku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yosuke", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Kubota", "name": null }, { "creator_type": "author", "first_name": "Riko", "last_name": "Kikuchi", "name": null }, { "creator_type": "author", "first_name": "Tomohiro", "last_name": "Yabushita", "name": null }, { "creator_type": "author", "first_name": "Takaharu", "last_name": "Kimura", "name": null }, { "creator_type": "author", "first_name": "Ivo", "last_name": "Lieberam", "name": null }, { "creator_type": "author", "first_name": "Jillian L.", "last_name": "Barlow", "name": null }, { "creator_type": "author", "first_name": "Josh W.", "last_name": "Bramley", "name": null }, { "creator_type": "author", "first_name": "Tsuyoshi", "last_name": "Fukushima", "name": null }, { "creator_type": "author", "first_name": "Chiaki", "last_name": "Sakuma", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Shibata", "name": null }, { "creator_type": "author", "first_name": "Masataka", "last_name": "Nakagawa", "name": null }, { "creator_type": "author", "first_name": "Yasunori", "last_name": "Kurosawa", "name": null }, { "creator_type": "author", "first_name": "Toshiaki", "last_name": "Maruyama", "name": null }, { "creator_type": "author", "first_name": "C. J.", "last_name": "Okumura", "name": null }, { "creator_type": "author", "first_name": "Yuichiro", "last_name": "Arima", "name": null }, { "creator_type": "author", "first_name": "Yoshinori", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Yasuo", "last_name": "Ono", "name": null }, { "creator_type": "author", "first_name": "Teruo", "last_name": "Akuta", "name": null }, { "creator_type": "author", "first_name": "Hidenobu", "last_name": "Mizuno", "name": null }, { "creator_type": "author", "first_name": "David G.", "last_name": "Kent", "name": null }, { "creator_type": "author", "first_name": "Thomas M.", "last_name": "Jessell", "name": null }, { "creator_type": "author", "first_name": "Susumu", "last_name": "Goyama", "name": null }, { "creator_type": "author", "first_name": "Hidekazu", "last_name": "Nishikii", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Kimura", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Yamazaki", "name": null }, { "creator_type": "author", "first_name": "Toshio", "last_name": "Suda", "name": null }, { "creator_type": "author", "first_name": "Toshio", "last_name": "Kitamura", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s42003-025-09242-x" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "41372396" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Separation", "descriptor_ui": "D002469", "major_topic": true }, { "descriptor": "Fetal Blood", "descriptor_ui": "D005312", "major_topic": false }, { "descriptor": "Flow Cytometry", "descriptor_ui": "D005434", "major_topic": false }, { "descriptor": "Gene Knock-In Techniques", "descriptor_ui": "D055879", "major_topic": false }, { "descriptor": "Green Fluorescent Proteins", "descriptor_ui": "D049452", "major_topic": false }, { "descriptor": "Hematopoietic Stem Cell Transplantation", "descriptor_ui": "D018380", "major_topic": false }, { "descriptor": "Hematopoietic Stem Cells", "descriptor_ui": "D006412", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false } ], "publication": { "conference_name": null, "date": "2025 Dec 10", "date_precision": "day", "issue": "", "normalized_date": "2025-12-10", "pages": "", "proceedings_title": null, "publisher": "", "title": "Communications biology", "volume": "", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Prospective isolation of mouse and human hematopoietic stem cells using PLXDC2.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "INTRODUCTION/AIMS: Denervation-induced muscle atrophy lacks effective therapies. Adipose-derived stem cells (ADSCs) show promise for tissue repair. This study aimed to evaluate the effect of local ADSC delivery on denervated muscle, investigate underlying mechanisms, and track ADSC distribution and migration in vivo. METHODS: In a mouse model of sciatic nerve transection and immediate reverse autograft repair, ADSCs or phosphate-buffered saline (PBS) were injected into the right gastrocnemius following nerve injury. Magnetic resonance imaging (MRI) and in vivo imaging system (IVIS) tracked ADSC migration. Muscle strength and gastrocnemius mass were measured. Histology (H&E, Masson), immunostaining (MyoD, CD163), and the real-time reverse transcription polymerase chain reaction (RT-PCR) assessed fiber size, fibrosis, muscle regeneration, M2 macrophage infiltration, and inflammatory gene expression. Endpoints were measured 1 week after the final injection (4 weeks post-injury). RESULTS: IVIS showed that injected ADSCs were visualized for 3-5 days in vivo while MRI localized cells predominantly to the quadriceps and knee regions. ADSC treatment increased normalized muscle strength (p < 0.05), normalized gastrocnemius muscle weight (p < 0.001) and fiber diameter (p < 0.05); downregulated MMP2 expression (p < 0.001), enhanced MyoD+ cell count (p < 0.001), and promoted M2 macrophage infiltration (CD163+ cells, p < 0.05; ARG1 mRNA, p < 0.05). RT-PCR revealed reduced pro-inflammatory transcripts (IL-6, IL-1b; p < 0.05). DISCUSSION: ADSCs ameliorate denervation-induced muscle atrophy by improving muscle function and structure via M2 macrophage infiltration, MyoD upregulation, MMP2 inhibition, and reduced inflammation. These findings underscore the therapeutic potential of ADSCs for mitigating muscle atrophy following nerve injury, although the acute injury model used may not fully represent chronic clinical denervation.", "classifications": [ { "id": "Kuchimaru", "label": "Group Kuchimaru", "parent": "Shintaku", "type": "group" }, { "id": "Shintaku", "label": "Team Shintaku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Qiannan", "last_name": "Zhao", "name": null }, { "creator_type": "author", "first_name": "Yoshihiro", "last_name": "Sowa", "name": null }, { "creator_type": "author", "first_name": "Ogawa", "last_name": "Koh", "name": null }, { "creator_type": "author", "first_name": "Yuanjiaozi", "last_name": "Li", "name": null }, { "creator_type": "author", "first_name": "Michiharu", "last_name": "Sakamoto", "name": null }, { "creator_type": "author", "first_name": "Shino", "last_name": "Higai", "name": null }, { "creator_type": "author", "first_name": "Yoshihiro", "last_name": "Toyohara", "name": null }, { "creator_type": "author", "first_name": "Takahiro", "last_name": "Kuchimaru", "name": null }, { "creator_type": "author", "first_name": "Tetsuji", "last_name": "Yamaoka", "name": null }, { "creator_type": "author", "first_name": "Naoki", "last_name": "Morimoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/mus.70094" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "41366198" } }, "mesh": [ { "descriptor": "Adipose Tissue", "descriptor_ui": "D000273", "major_topic": true }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Disease Models, Animal", "descriptor_ui": "D004195", "major_topic": false }, { "descriptor": "Inflammation", "descriptor_ui": "D007249", "major_topic": true }, { "descriptor": "Macrophages", "descriptor_ui": "D008264", "major_topic": true }, { "descriptor": "Magnetic Resonance Imaging", "descriptor_ui": "D008279", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Muscle, Skeletal", "descriptor_ui": "D018482", "major_topic": false }, { "descriptor": "Muscular Atrophy", "descriptor_ui": "D009133", "major_topic": true }, { "descriptor": "Sciatic Nerve", "descriptor_ui": "D012584", "major_topic": false }, { "descriptor": "Stem Cell Transplantation", "descriptor_ui": "D033581", "major_topic": true }, { "descriptor": "Stem Cells", "descriptor_ui": "D013234", "major_topic": true } ], "publication": { "conference_name": null, "date": "2025 Dec 9", "date_precision": "day", "issue": "", "normalized_date": "2025-12-09", "pages": "", "proceedings_title": null, "publisher": "", "title": "Muscle & nerve", "volume": "", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Adipose-Derived Stem Cells Alleviate Denervation-Induced Muscle Atrophy by Promoting M2 Macrophage Polarization and Reducing Inflammation.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: Compared with conventional chemotherapy, pembrolizumab-based chemoimmunotherapy (Pembro) and nivolumab plus ipilimumab with or without two cycles of platinum-doublet chemotherapy (Nivo+Ipi) improve survival in advanced non-small cell lung cancer (NSCLC). However, biomarkers for selecting optimal immunotherapy remain unclear. This study aimed to assess whether programmed cell death-ligand 1 (PD-L1) expression on tumor and immune cells (ICs) can guide first-line immunotherapy in advanced NSCLC. METHODS: This multicenter, observational study retrospectively reviewed patients with NSCLC treated with first-line Pembro or Nivo+Ipi who had evaluable PD-L1 expression on tumor (Tumor Proportion Score (TPS), 22C3) and ICs score (SP142). In addition, whole-exome and RNA sequencing were performed on treatment-naive NSCLCs with available PD-L1 expression status by both assays. RESULTS: Between 2019 and 2023, 198 patients were included (Pembro/Nivo+Ipi: 137/61). In the Pembro cohort, patients with high TPS (>/= 50%) had significantly longer progression-free survival (PFS) than those with low TPS (< 50%) (median PFS (mPFS, months): 8.1 vs 7.1; p=0.02), while IC score was not predictive. In the Nivo+Ipi cohort, high IC score (>/=1) was associated with longer PFS than low IC score (0) (mPFS: 7.7 vs 2.8; p=0.04), while TPS showed no impact. Among patients with low TPS/high IC scores, Nivo+Ipi achieved longer PFS than Pembro (mPFS: 12.4 vs 6.6; restricted mean survival time (RMST)(Nivo+Ipi)/RMST(Pembro) (24 months)=1.5; p=0.049). Multiomics analysis using 152 NSCLC samples showed that tumors with low TPS/high IC scores exhibited an activated tumor immune microenvironment comparable to that of tumors with high TPS. However, these tumors had significantly highest tumor mutation burden (TMB) and regulatory T cell (T(reg)) fraction among the PD-L1 phenotypes (median TMB (mut/Mb): 1.6 in tumors with low TPS/low IC score, 18.2 in low TPS/high IC score, and 1.9 in high TPS/any IC score; median T(reg) fraction (x10(-2)]: 0.0, 0.2, and 0.0, respectively), supporting a potential benefit of cytotoxic T-lymphocyte-associated antigen 4 blockade in addition to programmed cell death protein 1 (PD-1)/PD-L1 inhibition in this subgroup. CONCLUSIONS: Patients with NSCLC and low TPS/high IC scores may benefit more from Nivo+Ipi than from Pembro due to distinct genomic and immunological features, including high TMB and T(reg) fraction.", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Jun", "last_name": "Miyakoshi", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Yuji", "last_name": "Uehara", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Takeyasu", "name": null }, { "creator_type": "author", "first_name": "Masayuki", "last_name": "Shirasawa", "name": null }, { "creator_type": "author", "first_name": "Akito", "last_name": "Fukuda", "name": null }, { "creator_type": "author", "first_name": "Jumpei", "last_name": "Kashima", "name": null }, { "creator_type": "author", "first_name": "Shogo", "last_name": "Kumagai", "name": null }, { "creator_type": "author", "first_name": "Hidehito", "last_name": "Horinouchi", "name": null }, { "creator_type": "author", "first_name": "Hanako", "last_name": "Ono", "name": null }, { "creator_type": "author", "first_name": "Kouya", "last_name": "Shiraishi", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Kohno", "name": null }, { "creator_type": "author", "first_name": "Shunsuke", "last_name": "Kondo", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Goto", "name": null }, { "creator_type": "author", "first_name": "Noboru", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null }, { "creator_type": "author", "first_name": "Yukio", "last_name": "Hosomi", "name": null }, { "creator_type": "author", "first_name": "Takayasu", "last_name": "Kurata", "name": null }, { "creator_type": "author", "first_name": "Katsuhiko", "last_name": "Naoki", "name": null }, { "creator_type": "author", "first_name": "Takuji", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Yuichiro", "last_name": "Ohe", "name": null } ], "identifiers": { "doi": { "normalized": "10.1136/jitc-2025-012880" }, "pmcid": { "normalized": "PMC12684186" }, "pmid": { "normalized": "41360425" } }, "mesh": [ { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Aged, 80 and over", "descriptor_ui": "D000369", "major_topic": false }, { "descriptor": "B7-H1 Antigen", "descriptor_ui": "D060890", "major_topic": true }, { "descriptor": "Biomarkers, Tumor", "descriptor_ui": "D014408", "major_topic": true }, { "descriptor": "Carcinoma, Non-Small-Cell Lung", "descriptor_ui": "D002289", "major_topic": true }, { "descriptor": "CTLA-4 Antigen", "descriptor_ui": "D060908", "major_topic": true }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Immune Checkpoint Inhibitors", "descriptor_ui": "D000082082", "major_topic": true }, { "descriptor": "Immunotherapy", "descriptor_ui": "D007167", "major_topic": true }, { "descriptor": "Lung Neoplasms", "descriptor_ui": "D008175", "major_topic": true }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Phenotype", "descriptor_ui": "D010641", "major_topic": false }, { "descriptor": "Retrospective Studies", "descriptor_ui": "D012189", "major_topic": false } ], "publication": { "conference_name": null, "date": "2025 Dec 5", "date_precision": "day", "issue": "12", "normalized_date": "2025-12-05", "pages": "", "proceedings_title": null, "publisher": "", "title": "Journal for immunotherapy of cancer", "volume": "13", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "PD-L1 phenotype classification based on expression in tumor and immune cells as a potential biomarker for optimizing anti-PD-1/CTLA-4 immunotherapies in NSCLC.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Acute myeloid leukemia (AML) is characterized by the proliferation of malignant myeloid progenitor cells and impairment of hematopoiesis. Although genetic abnormalities within leukemic cells have been investigated in detail, definitive explanations for the damage to the normal hematopoietic system are lacking. Here, we investigated the mechanisms underlying the impairment of the residual hematopoietic system in the bone marrow in AML. We evaluated the function of residual non-leukemic (nl)-hematopoietic stem / progenitor cell (HSPC) from the bone marrow of mice with MLL-AF9-induced AML. The nl-HSPC in the leukemic marrow showed a megakaryocyte (MgK) and myeloid-biased gene expression signature, with enrichment of TNF signaling and reduced repopulation ability. To investigate whether the upregulation of TNF signaling causes the MgK / myeloid lineage bias, we investigated the effects of TNF-alpha in normal hematopoietic stem cells (HSC) / HSPC under ex-vivo expansion condition. Single-cell transcriptome analysis of these cells revealed an increased frequency of cells expressing genes related to the MgK lineage and decreased repopulation capacity compared with those of ex vivo-expanded HSC / HSPC without TNF-alpha. Our data suggest that increased TNF-alpha in the leukemic bone marrow environment at least in part drives HSPC toward MgK / myeloid differentiation, resulting in the exhaustion of residual normal HSC / HSPC. These findings offer valuable insights into leukemic biology and normal hematopoiesis.", "classifications": [ { "id": "Nishikii", "label": "Group Nishikii", "parent": "Shintaku", "type": "group" }, { "id": "Shintaku", "label": "Team Shintaku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Hidekazu", "last_name": "Nishikii", "name": null }, { "creator_type": "author", "first_name": "Riko", "last_name": "Kikuchi", "name": null }, { "creator_type": "author", "first_name": "Takaharu", "last_name": "Kimura", "name": null }, { "creator_type": "author", "first_name": "Mizuki", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Kiyoki", "name": null }, { "creator_type": "author", "first_name": "Saki", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Yamato", "last_name": "Sasaki", "name": null }, { "creator_type": "author", "first_name": "Takayasu", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Tatsuhiro", "last_name": "Sakamoto", "name": null }, { "creator_type": "author", "first_name": "Mamiko", "last_name": "Sakata-Yanagimoto", "name": null }, { "creator_type": "author", "first_name": "Naoshi", "last_name": "Obara", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Yamazaki", "name": null }, { "creator_type": "author", "first_name": "Shigeru", "last_name": "Chiba", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.exphem.2025.105332" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "41352655" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Lineage", "descriptor_ui": "D019070", "major_topic": true }, { "descriptor": "Hematopoietic Stem Cells", "descriptor_ui": "D006412", "major_topic": true }, { "descriptor": "Leukemia, Myeloid, Acute", "descriptor_ui": "D015470", "major_topic": true }, { "descriptor": "Megakaryocytes", "descriptor_ui": "D008533", "major_topic": true }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Myeloid Cells", "descriptor_ui": "D022423", "major_topic": true }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Tumor Microenvironment", "descriptor_ui": "D059016", "major_topic": true }, { "descriptor": "Tumor Necrosis Factor-alpha", "descriptor_ui": "D014409", "major_topic": true } ], "publication": { "conference_name": null, "date": "2025 Dec 4", "date_precision": "day", "issue": "", "normalized_date": "2025-12-04", "pages": "105332", "proceedings_title": null, "publisher": "", "title": "Experimental hematology", "volume": "", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Tumor necrosis factor from leukemic environment stimulates hematopoietic stem / progenitor cells toward megakaryocyte / myeloid lineage bias.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "In p16INK4a immunostaining, block positivity (i.e., strong nuclear/nuclear-cytoplasmic staining) is a widely acknowledged surrogate marker of HPV-associated cancers. Thus, immunohistochemistry using the anti-p16INK4a clone E6H4 has been approved as an in vitro diagnostic tool for HPV-associated cancers. This study revealed a distinctive pattern of immunostaining with clone E6H4-strong nuclear with nucleolar staining-which can easily be confused with the HPV-associated pattern. This peculiar pattern can be caused by frameshift deletions or insertions within exon 2 of the INK4a/ARF locus. Since p16INK4a and p14ARF are coded in the same sequence on chromosome 9p21, these mutations may inactivate p16INK4a and convert the reading frame for the 3' region of the p14ARF sequence into p16INK4a, producing a chimeric protein. Recognizing this pattern is essential to avoid misdiagnosis of HPV association and inappropriate treatment.", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Ayaka", "last_name": "Mitsui", "name": null }, { "creator_type": "author", "first_name": "Jumpei", "last_name": "Kashima", "name": null }, { "creator_type": "author", "first_name": "Eijitu", "last_name": "Ryo", "name": null }, { "creator_type": "author", "first_name": "Yukiko", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Toshihide", "last_name": "Ueno", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Mano", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null }, { "creator_type": "author", "first_name": "Taisuke", "last_name": "Mori", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/s00428-025-04365-2" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "41339993" } }, "mesh": [], "publication": { "conference_name": null, "date": "2025 Dec 4", "date_precision": "day", "issue": "", "normalized_date": "2025-12-04", "pages": "", "proceedings_title": null, "publisher": "", "title": "Virchows Archiv : an international journal of pathology", "volume": "", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Abnormal nuclear and nucleolar immunoreactivity of p16INK4a represents a frameshift alteration in CDKN2A: the E6H4 clone recognizes the \"p14ARF::p16INK4a\" chimeric protein.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "", "classifications": [ { "id": "Miyamichi", "label": "Group Miyamichi", "parent": "Enomoto", "type": "group" }, { "id": "Enomoto", "label": "Team Enomoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Kumi O.", "last_name": "Kuroda", "name": null }, { "creator_type": "author", "first_name": "Kazunari", "last_name": "Miyamichi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.neures.2025.105005" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "41349597" } }, "mesh": [], "publication": { "conference_name": null, "date": "2025 Dec 3", "date_precision": "day", "issue": "", "normalized_date": "2025-12-03", "pages": "105005", "proceedings_title": null, "publisher": "", "title": "Neuroscience research", "volume": "", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Neuroscience Research: Special issue Parental Brain: The Neural Circuit Mechanisms in Mammals.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Touchscreen-based operant learning systems are widely used in behavioral neuroscience to assess cognitive function across various animal models, including mice. However, conventional training protocols for visual discrimination (VD) tasks in mice often require extended training periods. We developed modified touchscreen training protocols that enhance learning efficiency in VD tasks. Our method requires mice to perform two or three consecutive screen touches to confirm their stimulus selection. If inconsistent responses occur during these touches, the trial is reset. This approach significantly improved task acquisition speed. Additionally, we incorporated visual feedback after incorrect choices, which further enhanced learning speed and task accuracy. Using this protocol, mice rapidly acquired both initial VD learning and reversal learning, even with multiple randomly presented stimulus pairs. Furthermore, in serial reversal tasks, mice exhibited improved performance across sessions, indicating rule acquisition and cognitive flexibility. These findings demonstrate that simple protocol adjustments can significantly improve touchscreen-based cognitive assessments in mice, enabling more cognitively demanding behavioral experiments in preclinical research.", "classifications": [ { "id": "Imayoshi", "label": "Group Imayoshi", "parent": "Imayoshi", "type": "group" }, { "id": "Imayoshi", "label": "Team Imayoshi", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yuji", "last_name": "Kiyama", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Misako", "last_name": "Haraguchi", "name": null }, { "creator_type": "author", "first_name": "Yukimura", "last_name": "Oe", "name": null }, { "creator_type": "author", "first_name": "Yukihisa", "last_name": "Daitoku", "name": null }, { "creator_type": "author", "first_name": "Natsumi", "last_name": "Higa", "name": null }, { "creator_type": "author", "first_name": "Yoshihiko", "last_name": "Irie", "name": null }, { "creator_type": "author", "first_name": "Takeru", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Itaru", "last_name": "Imayoshi", "name": null }, { "creator_type": "author", "first_name": "Masaki", "last_name": "Kakeyama", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Okuno", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41598-025-27003-y" }, "pmcid": { "normalized": "PMC12678427" }, "pmid": { "normalized": "41339645" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Behavior, Animal", "descriptor_ui": "D001522", "major_topic": false }, { "descriptor": "Cognition", "descriptor_ui": "D003071", "major_topic": false }, { "descriptor": "Conditioning, Operant", "descriptor_ui": "D003216", "major_topic": true }, { "descriptor": "Discrimination Learning", "descriptor_ui": "D004193", "major_topic": true }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Reversal Learning", "descriptor_ui": "D012193", "major_topic": false }, { "descriptor": "Visual Perception", "descriptor_ui": "D014796", "major_topic": true } ], "publication": { "conference_name": null, "date": "2025 Dec 3", "date_precision": "day", "issue": "1", "normalized_date": "2025-12-03", "pages": "43133", "proceedings_title": null, "publisher": "", "title": "Scientific reports", "volume": "15", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "A simple method that doubles learning speed for mice in touchscreen-based visual discrimination.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Neonatal hypoglycemia, a known risk factor for neurodevelopmental impairment, may result from maternal exposure to ritodrine, a beta(2)-adrenergic agonist used as a tocolytic agent to prevent preterm labor. We established a rodent model of ritodrine-induced neonatal hypoglycemia to elucidate mechanisms underlying this adverse effect. Ritodrine administration to pregnant rodents (dams) significantly decreased plasma glucose levels in their offspring (pups) 3 h after birth, compared with the phosphate-buffered saline (PBS) group. Although plasma insulin concentrations were significantly lower in the ritodrine group at birth, no significant differences were observed thereafter, suggesting this hypoglycemia is insulin-independent. Since blood glucose levels are regulated by a balance between peripheral glucose utilization and hepatic glucose production, we first assessed peripheral glucose uptake by measuring 2-deoxyglucose incorporation in the pup limbs. No significant differences were observed between the ritodrine and PBS groups. We next investigated whether the observed hypoglycemia was due to impaired hepatic glucose production. Hepatic glycogen content at birth was comparable between the two groups. Liver-targeted metabolomic analysis revealed that the rapid decline in gluconeogenesis (GNG)-related metabolites seen between 2 and 3 h after birth in the PBS group was absent in the ritodrine group. Furthermore, during GNG substrate tolerance tests, pups in the ritodrine group exhibited significantly lower blood glucose levels than those in the PBS group. Finally, hepatic expression of genes encoding gluconeogenic enzymes was significantly reduced in the ritodrine group. Overall, our findings demonstrate that ritodrine-induced neonatal hypoglycemia is caused by suppression of hepatic gluconeogenic enzyme expression in an insulin-independent manner.", "classifications": [ { "id": "Inaba", "label": "Group Inaba", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Mayu", "last_name": "Kajino", "name": null }, { "creator_type": "author", "first_name": "Arimi", "last_name": "Fujita", "name": null }, { "creator_type": "author", "first_name": "Rie", "last_name": "Nishizawa", "name": null }, { "creator_type": "author", "first_name": "Shoko", "last_name": "Shimokawa", "name": null }, { "creator_type": "author", "first_name": "Takahiro", "last_name": "Kawakami", "name": null }, { "creator_type": "author", "first_name": "Yuka", "last_name": "Inaba", "name": null }, { "creator_type": "author", "first_name": "Tsutomu", "last_name": "Shimada", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Inoue", "name": null }, { "creator_type": "author", "first_name": "Yoshimichi", "last_name": "Sai", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.bbrc.2025.153075" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "41351902" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Animals, Newborn", "descriptor_ui": "D000831", "major_topic": false }, { "descriptor": "Blood Glucose", "descriptor_ui": "D001786", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Gluconeogenesis", "descriptor_ui": "D005943", "major_topic": true }, { "descriptor": "Hypoglycemia", "descriptor_ui": "D007003", "major_topic": true }, { "descriptor": "Insulin", "descriptor_ui": "D007328", "major_topic": false }, { "descriptor": "Liver", "descriptor_ui": "D008099", "major_topic": true }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Maternal Exposure", "descriptor_ui": "D018811", "major_topic": false }, { "descriptor": "Pregnancy", "descriptor_ui": "D011247", "major_topic": false }, { "descriptor": "Prenatal Exposure Delayed Effects", "descriptor_ui": "D011297", "major_topic": true }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Rats, Sprague-Dawley", "descriptor_ui": "D017207", "major_topic": false }, { "descriptor": "Ritodrine", "descriptor_ui": "D012312", "major_topic": true } ], "publication": { "conference_name": null, "date": "2025 Dec 1", "date_precision": "day", "issue": "", "normalized_date": "2025-12-01", "pages": "153075", "proceedings_title": null, "publisher": "", "title": "Biochemical and biophysical research communications", "volume": "795", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Neonatal hypoglycemia triggered by maternal ritodrine administration is caused by inhibition of gluconeogenesis in the neonatal liver in rodents.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Patient-derived xenograft models are crucial in cancer research, although authentication methods remain limited. This study developed a comprehensive DNA profiling strategy for patient-derived xenograft quality control in the J-PDX Library by comparing short tandem repeat and single nucleotide polymorphism analyses. Overall, 325 patient-derived xenograft models were analyzed using both short tandem repeat and single nucleotide polymorphism profiling. Concordance rates between patient-derived samples and patient-derived xenograft models were assessed. Single nucleotide polymorphism-based analysis cutoffs classified models as matched, undeterminable, or unmatched. Additionally, the impact of microsatellite instability and loss of heterozygosity on concordance were evaluated. Short tandem repeat analysis showed greater variability than single nucleotide polymorphism analysis. Among the 325 models, 296 (91.1%) were matched, 24 (7.4%) were undeterminable, and five (1.5%) were unmatched. Notably, undeterminable models showed significantly higher microsatellite instability, with single nucleotide polymorphism analysis providing reliable authentication, even when short tandem repeat analysis failed. This study established an efficient patient-derived xenograft model quality control workflow using short tandem repeat analysis for primary screening and confirmatory single nucleotide polymorphism analysis for challenging cases, particularly microsatellite instability tumors. This workflow enables robust quality control of the J-PDX Library, enhancing its reliability for drug development and preclinical research.", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Tomomi", "last_name": "Yoshino", "name": null }, { "creator_type": "author", "first_name": "Shigehiro", "last_name": "Yagishita", "name": null }, { "creator_type": "author", "first_name": "Mami", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Chiaki", "last_name": "Ushie", "name": null }, { "creator_type": "author", "first_name": "Ako", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null }, { "creator_type": "author", "first_name": "Shinji", "last_name": "Kohsaka", "name": null }, { "creator_type": "author", "first_name": "Toshihide", "last_name": "Ueno", "name": null }, { "creator_type": "author", "first_name": "Hanako", "last_name": "Ono", "name": null }, { "creator_type": "author", "first_name": "Kouya", "last_name": "Shiraishi", "name": null }, { "creator_type": "author", "first_name": "Akinobu", "last_name": "Hamada", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41598-025-21299-6" }, "pmcid": { "normalized": "PMC12663538" }, "pmid": { "normalized": "41315486" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "DNA Fingerprinting", "descriptor_ui": "D016172", "major_topic": true }, { "descriptor": "Gene Library", "descriptor_ui": "D015723", "major_topic": false }, { "descriptor": "Heterografts", "descriptor_ui": "D064593", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Loss of Heterozygosity", "descriptor_ui": "D019656", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Microsatellite Instability", "descriptor_ui": "D053842", "major_topic": false }, { "descriptor": "Microsatellite Repeats", "descriptor_ui": "D018895", "major_topic": false }, { "descriptor": "Neoplasms", "descriptor_ui": "D009369", "major_topic": true }, { "descriptor": "Polymorphism, Single Nucleotide", "descriptor_ui": "D020641", "major_topic": false }, { "descriptor": "Quality Control", "descriptor_ui": "D011786", "major_topic": false }, { "descriptor": "Xenograft Model Antitumor Assays", "descriptor_ui": "D023041", "major_topic": false } ], "publication": { "conference_name": null, "date": "2025 Nov 28", "date_precision": "day", "issue": "1", "normalized_date": "2025-11-28", "pages": "42570", "proceedings_title": null, "publisher": "", "title": "Scientific reports", "volume": "15", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Comprehensive DNA profiling strategy for patient-derived xenograft model authentication in the J-PDX library.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Only 15% of young-onset breast cancers have identifiable hereditary germline pathogenic variants (PVs) in an established breast cancer susceptibility gene. However, it is believed that a significant proportion of these breast cancers have additional monogenic or rare risk variants that require identification. To uncover novel cancer susceptibility genes, we performed germline whole-exome/genome sequencing of samples from 564 patients with young-onset breast cancer (aged <40 years), as well as samples from 4032 female controls. The identified candidate variants were further genotyped in 6,967 independent breast cancer cases across all age groups. We identified two PVs that were significantly associated with the risk of hormone receptor-negative young-onset breast cancer: POLH p.K589T (OR = 3.65, 95% confidence interval [CI] = 1.28-10.4, P = 0.0095) and RAD51 p.M1fs (OR = 2.15, 95% CI = 1.15-4.02, P = 0.014). When BRCA1/2 PV carriers were excluded from the analysis, only RAD51 p.M1fs retained a significant association. Whole-genome sequencing of tumor samples carrying these germline risk variants revealed that they harbored mutational signatures indicative of a deficiency of homologous recombination. These findings suggest that hereditary POLH p.K589T and RAD51 p.M1fs are candidate variants associated with an increased risk of hormone receptor-negative breast cancer.", "classifications": [ { "id": "Hamamoto", "label": "Group Hamamoto", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Shu", "last_name": "Yazaki", "name": null }, { "creator_type": "author", "first_name": "Rui", "last_name": "Kitadai", "name": null }, { "creator_type": "author", "first_name": "Yukihide", "last_name": "Momozawa", "name": null }, { "creator_type": "author", "first_name": "Teruhiko", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Yamanaka", "name": null }, { "creator_type": "author", "first_name": "Sho", "last_name": "Shiino", "name": null }, { "creator_type": "author", "first_name": "Chisako", "last_name": "Yamauchi", "name": null }, { "creator_type": "author", "first_name": "Kenichi", "last_name": "Harano", "name": null }, { "creator_type": "author", "first_name": "Motonobu", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Yosuke", "last_name": "Hirotsu", "name": null }, { "creator_type": "author", "first_name": "Hisaki", "last_name": "Aiba", "name": null }, { "creator_type": "author", "first_name": "Ryuji", "last_name": "Hamamoto", "name": null }, { "creator_type": "author", "first_name": "Chikako", "last_name": "Shimizu", "name": null }, { "creator_type": "author", "first_name": "Akihiko", "last_name": "Shimomura", "name": null }, { "creator_type": "author", "first_name": "Tatsunori", "last_name": "Shimoi", "name": null }, { "creator_type": "author", "first_name": "Kazuki", "last_name": "Sudo", "name": null }, { "creator_type": "author", "first_name": "Masayuki", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Kuniko", "last_name": "Sunami", "name": null }, { "creator_type": "author", "first_name": "Yuichi", "last_name": "Shiraishi", "name": null }, { "creator_type": "author", "first_name": "Aya", "last_name": "Kuchiba", "name": null }, { "creator_type": "author", "first_name": "Megumi", "last_name": "Hori", "name": null }, { "creator_type": "author", "first_name": "Kota", "last_name": "Katanoda", "name": null }, { "creator_type": "author", "first_name": "Sadaaki", "last_name": "Takata", "name": null }, { "creator_type": "author", "first_name": "Ayumi", "last_name": "Ogawa", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Torasawa", "name": null }, { "creator_type": "author", "first_name": "Akifumi", "last_name": "Mochizuki", "name": null }, { "creator_type": "author", "first_name": "Yoko", "last_name": "Shimada", "name": null }, { "creator_type": "author", "first_name": "Kengo", "last_name": "Hiranuma", "name": null }, { "creator_type": "author", "first_name": "Erisa", "last_name": "Fujii", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Hirata", "name": null }, { "creator_type": "author", "first_name": "Yuji", "last_name": "Yamashita", "name": null }, { "creator_type": "author", "first_name": "Takahiro", "last_name": "Kogawa", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Murata", "name": null }, { "creator_type": "author", "first_name": "Saori", "last_name": "Fujiwara", "name": null }, { "creator_type": "author", "first_name": "Yohei", "last_name": "Miyagi", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Nakagomi", "name": null }, { "creator_type": "author", "first_name": "Kazunoshin", "last_name": "Tachibana", "name": null }, { "creator_type": "author", "first_name": "Koichi", "last_name": "Matsuda", "name": null }, { "creator_type": "author", "first_name": "Yoshinori", "last_name": "Murakami", "name": null }, { "creator_type": "author", "first_name": "Katsushi", "last_name": "Tokunaga", "name": null }, { "creator_type": "author", "first_name": "Yosuke", "last_name": "Kawai", "name": null }, { "creator_type": "author", "first_name": "Biobank Japan", "last_name": "Project", "name": null }, { "creator_type": "author", "first_name": "Masao", "last_name": "Omata", "name": null }, { "creator_type": "author", "first_name": "Tohru", "last_name": "Ohtake", "name": null }, { "creator_type": "author", "first_name": "Akihiko", "last_name": "Suto", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Onishi", "name": null }, { "creator_type": "author", "first_name": "Yoichi", "last_name": "Naito", "name": null }, { "creator_type": "author", "first_name": "Toshinari", "last_name": "Yamashita", "name": null }, { "creator_type": "author", "first_name": "Kan", "last_name": "Yonemori", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Kohno", "name": null }, { "creator_type": "author", "first_name": "Kouya", "last_name": "Shiraishi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41523-025-00848-2" }, "pmcid": { "normalized": "PMC12663359" }, "pmid": { "normalized": "41315479" } }, "mesh": [], "publication": { "conference_name": null, "date": "2025 Nov 28", "date_precision": "day", "issue": "1", "normalized_date": "2025-11-28", "pages": "133", "proceedings_title": null, "publisher": "", "title": "NPJ breast cancer", "volume": "11", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Germline variants of the POLH and RAD51 genes are candidate variants associated with risk of hormone receptor-negative young-onset breast cancer.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Supersulfide species have been identified as molecules that have catenated sulfur atoms as persulfides (R-SSH) and polysulfides (R-SS(n)H). The physiological activities of intracellular supersulfides have been widely studied, but little is known about the role of supersulfides in extracellular biological fluids. We therefore analyzed the pathological changes and oxidative stress responses of the reduced and oxidized forms of polysulfides in the plasma of patients with diabetic nephropathy. We measured the reduced and oxidized forms of polysulfide with elimination of sulfides using dithiothreitol and ascorbic acid plus alkali conditions, respectively. Oxidation decreased oxidized forms of polysulfide and further polysulfide in human serum albumin, increasing its antioxidative activity. We identified seven cysteine residues that have polysulfides in a reduced form after oxidation in albumin. Further oxidation decreased the levels of the reduced forms of polysulfide and the antioxidative effect of serum albumin. Similar changes were also observed in a mouse model of rhabdomyolysis-induced acute kidney injury; the levels of reduced polysulfide in plasma transiently increased 1 h after glycerol administration, which was accompanied by increased antioxidative activity. In the sera of patients with diabetic nephropathy and chronic renal failure, both forms of polysulfides were decreased compared with those of healthy subjects. Analysis of the stages of renal damage revealed that dithiothreitol-liberated polysulfide increased from stages 1-3 and decreased in stage 5. These results suggest that the antioxidative activity of serum, including that of serum albumin, is regulated by the switch from the oxidized form of polysulfide to its reduced counterparts in response to oxidative stress.", "classifications": [ { "id": "Akaike", "label": "Group Akaike", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Mayumi", "last_name": "Ikeda-Imafuku", "name": null }, { "creator_type": "author", "first_name": "Maki", "last_name": "Sakai", "name": null }, { "creator_type": "author", "first_name": "Keitaro", "last_name": "Umezawa", "name": null }, { "creator_type": "author", "first_name": "Hidehiko", "last_name": "Nakagawa", "name": null }, { "creator_type": "author", "first_name": "Toru", "last_name": "Maruyama", "name": null }, { "creator_type": "author", "first_name": "Masaki", "last_name": "Otagiri", "name": null }, { "creator_type": "author", "first_name": "Takaaki", "last_name": "Akaike", "name": null }, { "creator_type": "author", "first_name": "Tomohiro", "last_name": "Sawa", "name": null }, { "creator_type": "author", "first_name": "Ming", "last_name": "Xian", "name": null }, { "creator_type": "author", "first_name": "Yuri", "last_name": "Miura", "name": null }, { "creator_type": "author", "first_name": "Tatsuhiro", "last_name": "Ishida", "name": null }, { "creator_type": "author", "first_name": "Yu", "last_name": "Ishima", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41598-025-26702-w" }, "pmcid": { "normalized": "PMC12663333" }, "pmid": { "normalized": "41309823" } }, "mesh": [ { "descriptor": "Acute Kidney Injury", "descriptor_ui": "D058186", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Antioxidants", "descriptor_ui": "D000975", "major_topic": false }, { "descriptor": "Diabetic Nephropathies", "descriptor_ui": "D003928", "major_topic": true }, { "descriptor": "Disease Models, Animal", "descriptor_ui": "D004195", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Oxidation-Reduction", "descriptor_ui": "D010084", "major_topic": false }, { "descriptor": "Oxidative Stress", "descriptor_ui": "D018384", "major_topic": true }, { "descriptor": "Serum Albumin", "descriptor_ui": "D012709", "major_topic": true }, { "descriptor": "Serum Albumin, Human", "descriptor_ui": "D000075462", "major_topic": false }, { "descriptor": "Sulfides", "descriptor_ui": "D013440", "major_topic": true } ], "publication": { "conference_name": null, "date": "2025 Nov 27", "date_precision": "day", "issue": "1", "normalized_date": "2025-11-27", "pages": "42689", "proceedings_title": null, "publisher": "", "title": "Scientific reports", "volume": "15", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Unique response of polysulfide in serum albumin to oxidative stress.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Liquid-liquid phase separation (LLPS) is a phenomenon where homogeneous solutions of biomacromolecules separate into two liquid phases and generate liquid droplets enriched in specific biomolecules. LLPS of neurodegeneration-related proteins, including fused in sarcoma (FUS), promotes their aggregation, causing fatal diseases such as amyotrophic lateral sclerosis (ALS). Recent studies showed that RNAs regulate LLPS of these proteins and inhibit their aggregation, which may play an important role in preventing the disease onset; however, the underlying molecular mechanisms remain elusive. It is also unknown whether endogenous RNAs regulate LLPS and subsequent aggregation in cells. In this study, we investigated features of RNAs that enable their entrance into FUS droplets and inhibition of FUS aggregation via droplets and clarified the underlying mechanisms using Raman microscopy. We found that RNA length is one of the primary factors governing both the aggregation-inhibition effect and the localization of RNAs in the droplets in buffer solutions. Short (<50-nt) RNAs were concentrated inside the droplets and inhibited the aggregation. Our quantification method using Raman microscopy revealed that the short RNAs are enriched in FUS droplets by binding to FUS proteins through electrostatic interactions. On the other hand, long (>1000-nt) RNAs were not concentrated and dissolved the droplets. Raman imaging of living cells revealed that intracellular FUS droplets are enriched with endogenous RNAs at levels comparable to in vitro droplets and exhibit high fluidity, confirming that endogenous RNAs play a crucial role in suppressing droplet-to-aggregate transition of FUS in cells. These findings indicate that short RNAs stabilize FUS droplets through heterotypic RNA-FUS interactions that compete with homotypic FUS-FUS direct contacts responsible for aggregation, whereas binding of long RNAs enhances FUS solubility and promotes droplet dissolution. Our study highlights the protective role of RNAs against pathogenic aggregation of neurodegeneration-related proteins via droplets.", "classifications": [ { "id": "Nakabayashi", "label": "Group Nakabayashi", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Taisei", "last_name": "Ogura", "name": null }, { "creator_type": "author", "first_name": "Uchu", "last_name": "Matsuura", "name": null }, { "creator_type": "author", "first_name": "Masato", "last_name": "Machida", "name": null }, { "creator_type": "author", "first_name": "Kaichi", "last_name": "Nagai", "name": null }, { "creator_type": "author", "first_name": "Shinji", "last_name": "Kajimoto", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Tahara", "name": null }, { "creator_type": "author", "first_name": "Takakazu", "last_name": "Nakabayashi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/jacsau.5c01234" }, "pmcid": { "normalized": "PMC12648311" }, "pmid": { "normalized": "41311968" } }, "mesh": [], "publication": { "conference_name": null, "date": "2025 Nov 24", "date_precision": "day", "issue": "11", "normalized_date": "2025-11-24", "pages": "5749-5757", "proceedings_title": null, "publisher": "", "title": "JACS Au", "volume": "5", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "RNA-Mediated Inhibition Mechanism of Liquid-Liquid Phase Separation and Subsequent Aggregation Revealed by Raman Microscopy.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Thyroid transcription factor-1 (TTF-1) is expressed in the thyroid gland, lungs, and brain, and has also been reported in thymomas. While some studies have suggested TTF-1 as a specific marker for type AB thymoma, others have noted significant variability, often due to small case numbers. In this study, TTF-1 expression was evaluated in 50 cases of type A and AB thymomas using three distinct clones (8G7G3/1, SPT24, and SP141), and quantified with a four-grade scale. Additionally, CD20 expression and GTF2I mutation status were analyzed. TTF-1 expression analyses with the SPT24 and SP141 clones yielded a score of 3 (defined as positivity in >50 % of cells) in 20 % and 18 % of thymomas, respectively. In contrast, the 8G7G3/1 clone showed a score of 0 (positivity in <1 % of cells) across all tumors. There were no differences in score 3 positivity between type A and type AB thymomas for either the SPT24 or SP141 clones. Additionally, no statistically significant associations were identified between clinicopathological characteristics or GTF2I mutations and score 3 versus score /= 0.72 accurately predicted lymph node metastasis and improved concordance between AI and radiologist solid tumour assessment while maintaining a similar PathoiD/tD to the conventional (cD/tD = 1.0) threshold. Among tumors measuring /= 0.72 showed potential for predicting lymph node metastasis in this single-center retrospective study of lung adenocarcinoma /= 1 was a significant factor of shorter OS and higher CI-IFR, and a mean heart dose >/= 7.5 Gy showed a trend toward significance for shorter OS., Internal high-dose volumetric modulated arc therapy was associated with lower CI-R, whereas poor baseline performance status correlated with higher CI-DM. Notably, durvalumab administration was marginally associated with lower CI-R. CONCLUSIONS: Pre-treatment ILA and high mean heart doses negatively impacted OS in patients with LA-NSCLC with negative or low PD-L1 expression according to real-world data obtained after the PACIFIC trial. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13014-025-02733-5.", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Tairo", "last_name": "Kashihara", "name": null }, { "creator_type": "author", "first_name": "Yuko", "last_name": "Nakayama", "name": null }, { "creator_type": "author", "first_name": "Kae", "last_name": "Okuma", "name": null }, { "creator_type": "author", "first_name": "Ayaka", "last_name": "Nagao", "name": null }, { "creator_type": "author", "first_name": "Kana", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Tomoya", "last_name": "Kaneda", "name": null }, { "creator_type": "author", "first_name": "Yuko", "last_name": "Kubo", "name": null }, { "creator_type": "author", "first_name": "Kimiteru", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Okamoto", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null }, { "creator_type": "author", "first_name": "Masahiko", "last_name": "Kusumoto", "name": null }, { "creator_type": "author", "first_name": "Yuichiro", "last_name": "Ohe", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Igaki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1186/s13014-025-02733-5" }, "pmcid": { "normalized": "PMC12529796" }, "pmid": { "normalized": "41102751" } }, "mesh": [ { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Aged, 80 and over", "descriptor_ui": "D000369", "major_topic": false }, { "descriptor": "B7-H1 Antigen", "descriptor_ui": "D060890", "major_topic": true }, { "descriptor": "Carcinoma, Non-Small-Cell Lung", "descriptor_ui": "D002289", "major_topic": true }, { "descriptor": "Chemoradiotherapy", "descriptor_ui": "D059248", "major_topic": true }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Lung Neoplasms", "descriptor_ui": "D008175", "major_topic": true }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Neoplasm Recurrence, Local", "descriptor_ui": "D009364", "major_topic": false }, { "descriptor": "Prognosis", "descriptor_ui": "D011379", "major_topic": false } ], "publication": { "conference_name": null, "date": "2025 Oct 16", "date_precision": "day", "issue": "1", "normalized_date": "2025-10-16", "pages": "155", "proceedings_title": null, "publisher": "", "title": "Radiation oncology (London, England)", "volume": "20", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Locally advanced non-small cell lung cancer with negative or low programmed death ligand 1 expression: a prognostic factor analysis of real-world data after the PACIFIC trial.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Machine learning studies for Raman imaging have addressed the differentiability of normal and diseased states in biomedical applications by grouping a set of Raman spectra in terms of spectral similarity over the sample. However, Raman imaging provides both chemical information relevant to the underlying chemical species and their spatial distribution across the biological samples. Utilizing both the chemical and spatial information may further discriminate the sample states more than just using the spectral similarity free from the spatial structure. Here, we develop a Raman image analysis method integrating spatial and chemical information. The crux of our method is to introduce a measure to quantify spatial heterogeneity among Raman spectra at each pixel, and to classify Raman images using information theory, based not directly on the Raman spectra themselves at individual pixels but on the spatial heterogeneity in the spectral space over the surroundings. In this paper, we applied the method to a set of liver tissues dissected from non-alcoholic fatty liver disease (NAFLD) rat model, each of which is pathologically classified into normal, nonalcoholic fatty liver (NAFL) and non-alcoholic steatohepatitis (NASH), respectively. We show how the pathologically-identified liver states can be further classified using chemical information, and both chemical and spatial information. All NASH tissues that are belonging to a same cluster in spectral similarity are found to be further divided into substates that correlate the progression of the NAFLD disease, and subtle contamination of bloods that often prevents from appropriate pathological judgments. The potential of a use of both chemical and spatial information in Raman imaging is expected to enhance the differentiability of disease states of biological samples.", "classifications": [ { "id": "Fujita", "label": "Group Fujita", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Ryoya", "last_name": "Kondo", "name": null }, { "creator_type": "author", "first_name": "Yuta", "last_name": "Mizuno", "name": null }, { "creator_type": "author", "first_name": "Kentaro", "last_name": "Mochizuki", "name": null }, { "creator_type": "author", "first_name": "Kosuke", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Jean-Emmanuel", "last_name": "Clement", "name": null }, { "creator_type": "author", "first_name": "Yasuaki", "last_name": "Kumamoto", "name": null }, { "creator_type": "author", "first_name": "Katsumasa", "last_name": "Fujita", "name": null }, { "creator_type": "author", "first_name": "Yoshinori", "last_name": "Harada", "name": null }, { "creator_type": "author", "first_name": "Tamiki", "last_name": "Komatsuzaki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41598-025-17495-z" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "41083533" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Disease Models, Animal", "descriptor_ui": "D004195", "major_topic": false }, { "descriptor": "Image Processing, Computer-Assisted", "descriptor_ui": "D007091", "major_topic": false }, { "descriptor": "Liver", "descriptor_ui": "D008099", "major_topic": false }, { "descriptor": "Machine Learning", "descriptor_ui": "D000069550", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Non-alcoholic Fatty Liver Disease", "descriptor_ui": "D065626", "major_topic": true }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Spectrum Analysis, Raman", "descriptor_ui": "D013059", "major_topic": true } ], "publication": { "conference_name": null, "date": "2025 Oct 13", "date_precision": "day", "issue": "1", "normalized_date": "2025-10-13", "pages": "35216", "proceedings_title": null, "publisher": "", "title": "Scientific reports", "volume": "15", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Integrating spatial and chemical information enhances differentiation of non-alcoholic steatohepatitis states in Raman imaging.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "OBJECTIVE: Occult lymph node (LN) metastasis, indicating pathological LN involvement, is often observed in clinical N0 (cN0) early-stage non-small cell lung cancer (NSCLC). Identifying preoperative predictors of occult LN metastasis (pathologically N1 and N2) is crucial for determining the surgical procedure for cN0 NSCLC. This study aimed to investigate the role of genetic mutations in predicting occult LN metastasis and their influence on surgical strategies. MATERIALS AND METHODS: We retrospectively reviewed patients who underwent lobectomy or segmentectomy for cN0 NSCLC with pathological stages higher than IB, between May 2017 and April 2024. Clinicopathological characteristics and genetic mutations were analyzed. Occult LN metastasis was not detected by imaging but identified through histopathology. RESULTS: We evaluated 644 patients, median age 71 years. Occult LN metastases were observed in 179 (27.8%) patients. EGFR mutations and ALK rearrangements were significantly associated with occult LN metastasis (EGFR, P = .04; ALK, P = .007), particularly EGFR exon 19 deletions (P = .006). Multivariate analysis confirmed these as significant predictors (P = .006). Notably, patients with these mutations had longer recurrence-free survival (RFS) than those without (HR 1.27, 95% CI, 0.90-1.80, P = .02). For patients with EGFR mutations and ALK rearrangements, RFS was significantly shorter after segmentectomy (HR 3.18, 95% CI, 1.02-9.99, P = .04) and longer after lobectomy (HR 1.28, 95% CI, 0.87-1.90, P = .01). CONCLUSION: Genomic profiles, such as EGFR mutations and ALK rearrangements, are associated with occult LN metastasis and outcomes in cN0 NSCLC. Integrating genetic assessments into preoperative planning may optimize surgical strategies and improve prognosis.", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Chihiro", "last_name": "Takemura", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Yukihiro", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Ryoko Inaba", "last_name": "Higashiyama", "name": null }, { "creator_type": "author", "first_name": "Hidehito", "last_name": "Horinouchi", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Igaki", "name": null }, { "creator_type": "author", "first_name": "Noboru", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Yuichiro", "last_name": "Ohe", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null }, { "creator_type": "author", "first_name": "Shun-Ichi", "last_name": "Watanabe", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.cllc.2025.10.002" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "41177713" } }, "mesh": [ { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Aged, 80 and over", "descriptor_ui": "D000369", "major_topic": false }, { "descriptor": "Anaplastic Lymphoma Kinase", "descriptor_ui": "D000077548", "major_topic": false }, { "descriptor": "Biomarkers, Tumor", "descriptor_ui": "D014408", "major_topic": true }, { "descriptor": "Carcinoma, Non-Small-Cell Lung", "descriptor_ui": "D002289", "major_topic": true }, { "descriptor": "ErbB Receptors", "descriptor_ui": "D066246", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Follow-Up Studies", "descriptor_ui": "D005500", "major_topic": false }, { "descriptor": "Genomics", "descriptor_ui": "D023281", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Lung Neoplasms", "descriptor_ui": "D008175", "major_topic": true }, { "descriptor": "Lymphatic Metastasis", "descriptor_ui": "D008207", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": false }, { "descriptor": "Neoplasm Staging", "descriptor_ui": "D009367", "major_topic": false }, { "descriptor": "Pneumonectomy", "descriptor_ui": "D011013", "major_topic": false }, { "descriptor": "Prognosis", "descriptor_ui": "D011379", "major_topic": false }, { "descriptor": "Retrospective Studies", "descriptor_ui": "D012189", "major_topic": false }, { "descriptor": "Survival Rate", "descriptor_ui": "D015996", "major_topic": false } ], "publication": { "conference_name": null, "date": "2025 Oct 10", "date_precision": "day", "issue": "", "normalized_date": "2025-10-10", "pages": "S1525-7304(25)00242-6", "proceedings_title": null, "publisher": "", "title": "Clinical lung cancer", "volume": "", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Genomic Profiles as Predictors of Occult Lymph Node Metastasis and Clinical Outcomes in Early-Stage Clinical N0 Non-Small Cell Lung Cancer.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Within each cell, metabolite-sensing factors respond to coordinate metabolic homeostasis. How metabolic homeostasis is regulated intercellularly and how this may become dysregulated with age, however, remains underexplored. Here we describe a system regulated by a metabolite sensor, CtBP2. CtBP2 is secreted via exosomes in response to reductive metabolism, which is suppressed by oxidative stress. Exosomal CtBP2 administration extends lifespan in aged mice and improves healthspan in particular by reducing frailty. Mechanistically, we identify activation of CYB5R3 and AMPK downstream of exosomal CtBP2. Consistently, serum CtBP2 levels decrease with age and are negatively associated with cardiovascular disease incidence in humans yet are elevated in individuals from families with a history of longevity. Together our findings define a CtBP2-mediated metabolic system with potential for future clinical applications.", "classifications": [ { "id": "Miyamoto", "label": "Group Miyamoto", "parent": "Wakamoto", "type": "group" }, { "id": "Wakamoto", "label": "Team Wakamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Motohiro", "last_name": "Sekiya", "name": null }, { "creator_type": "author", "first_name": "Kenta", "last_name": "Kainoh", "name": null }, { "creator_type": "author", "first_name": "Wanpei", "last_name": "Chen", "name": null }, { "creator_type": "author", "first_name": "Daichi", "last_name": "Yamazaki", "name": null }, { "creator_type": "author", "first_name": "Tomomi", "last_name": "Tsuyuzaki", "name": null }, { "creator_type": "author", "first_name": "Yuto", "last_name": "Kobari", "name": null }, { "creator_type": "author", "first_name": "Ayumi", "last_name": "Nakata", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Nao", "last_name": "Aono-Soma", "name": null }, { "creator_type": "author", "first_name": "Ali", "last_name": "Majid", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Ohno", "name": null }, { "creator_type": "author", "first_name": "Takafumi", "last_name": "Miyamoto", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Matsuzaka", "name": null }, { "creator_type": "author", "first_name": "Rikako", "last_name": "Nakajima", "name": null }, { "creator_type": "author", "first_name": "Takaaki", "last_name": "Matsuda", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Murayama", "name": null }, { "creator_type": "author", "first_name": "Yoko", "last_name": "Sugano", "name": null }, { "creator_type": "author", "first_name": "Yoshinori", "last_name": "Osaki", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Iwasaki", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Shimano", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s43587-025-00973-4" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "41062862" } }, "mesh": [ { "descriptor": "Alcohol Oxidoreductases", "descriptor_ui": "D000429", "major_topic": true }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cardiovascular Diseases", "descriptor_ui": "D002318", "major_topic": false }, { "descriptor": "Co-Repressor Proteins", "descriptor_ui": "D056970", "major_topic": true }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Healthy Aging", "descriptor_ui": "D000073656", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Longevity", "descriptor_ui": "D008136", "major_topic": true }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Oxidative Stress", "descriptor_ui": "D018384", "major_topic": false } ], "publication": { "conference_name": null, "date": "2025 Oct 8", "date_precision": "day", "issue": "", "normalized_date": "2025-10-08", "pages": "", "proceedings_title": null, "publisher": "", "title": "Nature aging", "volume": "", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "The secreted metabolite sensor CtBP2 links metabolism to healthy lifespan.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND & AIMS: Mucosal immune alteration is a characteristic clinical manifestation of irritable bowel syndrome (IBS), and its symptoms are often triggered by psychological stress. The present study aimed to investigate the impact of early life stress-associated dysfunction of the sympathetic nervous system (SNS) on mucosal immune changes in the gastrointestinal tract (GI) and its contribution to visceral hypersensitivity of IBS. METHODS: We utilized a traditional animal model of IBS with maternal separation (MS) and evaluated colorectal hypersensitivity, immune alteration, and SNS activity in adult rats with MS. We conducted a series of experiments to manipulate peripheral SNS activity pharmacologically and chemogenetically to explore the interaction between SNS activity and GI events. RESULTS: The MS-induced IBS model exhibited visceral hypersensitivity and eosinophilic infiltration in the colonic mucosa, along with SNS overactivation. Degeneration of the SNS using 6-OHDA neurotoxin decreased eosinophil infiltration and visceral hypersensitivity in the MS model. Notably, specific chemogenetic activation of the peripheral SNS induced eosinophil infiltration in the intestinal mucosa through the noradrenergic signalling-mediated release of eotaxin-1 from mesenchymal cells. CONCLUSION: This study highlights the critical role of SNS overactivation in eotaxin-1-driven eosinophil infiltration in the colon, leading to the development of visceral hypersensitivity in IBS. The results provide important insights into the mechanistic links among increased sympathetic activity, mucosal immune alteration, and visceral hypersensitivity in individuals with IBS, suggesting potential therapeutic approaches.", "classifications": [ { "id": "Miyamichi", "label": "Group Miyamichi", "parent": "Enomoto", "type": "group" }, { "id": "Enomoto", "label": "Team Enomoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Shaoqi", "last_name": "Duan", "name": null }, { "creator_type": "author", "first_name": "Hirosato", "last_name": "Kanda", "name": null }, { "creator_type": "author", "first_name": "Feng", "last_name": "Zhu", "name": null }, { "creator_type": "author", "first_name": "Masamichi", "last_name": "Okubo", "name": null }, { "creator_type": "author", "first_name": "Taro", "last_name": "Koike", "name": null }, { "creator_type": "author", "first_name": "Yoshiya", "last_name": "Ohno", "name": null }, { "creator_type": "author", "first_name": "Toshiyuki", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Yukiko", "last_name": "Harima", "name": null }, { "creator_type": "author", "first_name": "Kazunari", "last_name": "Miyamichi", "name": null }, { "creator_type": "author", "first_name": "Hirokazu", "last_name": "Fukui", "name": null }, { "creator_type": "author", "first_name": "Shinichiro", "last_name": "Shinzaki", "name": null }, { "creator_type": "author", "first_name": "Yilong", "last_name": "Cui", "name": null }, { "creator_type": "author", "first_name": "Koichi", "last_name": "Noguchi", "name": null }, { "creator_type": "author", "first_name": "Yi", "last_name": "Dai", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.jcmgh.2025.101658" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "41067576" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Chemokine CCL11", "descriptor_ui": "D054413", "major_topic": false }, { "descriptor": "Colon", "descriptor_ui": "D003106", "major_topic": true }, { "descriptor": "Disease Models, Animal", "descriptor_ui": "D004195", "major_topic": false }, { "descriptor": "Eosinophils", "descriptor_ui": "D004804", "major_topic": true }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Intestinal Mucosa", "descriptor_ui": "D007413", "major_topic": false }, { "descriptor": "Irritable Bowel Syndrome", "descriptor_ui": "D043183", "major_topic": true }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Rats, Sprague-Dawley", "descriptor_ui": "D017207", "major_topic": false }, { "descriptor": "Stress, Psychological", "descriptor_ui": "D013315", "major_topic": false }, { "descriptor": "Sympathetic Nervous System", "descriptor_ui": "D013564", "major_topic": true } ], "publication": { "conference_name": null, "date": "2025 Oct 7", "date_precision": "day", "issue": "", "normalized_date": "2025-10-07", "pages": "101658", "proceedings_title": null, "publisher": "", "title": "Cellular and molecular gastroenterology and hepatology", "volume": "", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Sympathetic Overactivation Drives Colonic Eosinophil Infiltration Linked to Visceral Hypersensitivity in Irritable Bowel Syndrome.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: Lung adenocarcinoma (LUAD) in never-smokers is a major public health burden, especially among East Asian women. Polygenic risk scores (PRSs) are promising for risk stratification but are primarily developed in European-ancestry populations. We aimed to develop and validate single- and multi-ancestry PRSs for East Asian never-smokers to improve LUAD risk prediction. METHODS: PRSs were developed using genome-wide association study summary statistics from East Asian (8,002 cases; 20,782 controls) and European (2,058 cases; 5,575 controls) populations. Single-ancestry models included PRS-25, PRS-CT, and LDpred2; multi-ancestry models included LDpred2+PRS-EUR128, PRS-CSx, and CT-SLEB. Performance was evaluated in independent East Asian data from the Female Lung Cancer Consortium (FLCCA) and externally validated in the Nanjing Lung Cancer Cohort (NJLCC). We assessed predictive accuracy via AUC, with 10-year and (age 30-80) absolute risks estimates. RESULTS: The best multi-ancestry PRS, using East Asian and European data via CT-SLEB (clumping and thresholding, super learning, empirical Bayes), outperformed the best East Asian-only PRS (LDpred2; AUC = 0.629, 95% CI:0.618,0.641), achieving an AUC of 0.640 (95% CI : 0.629,0.653) and odds ratio of 1.71 (95% CI : 1.61,1.82) per SD increase. NJLCC Validation confirmed robust performance (AUC =0.649, 95% CI: 0.623, 0.676). The top 20% PRS group had a 3.92-fold higher LUAD risk than the bottom 20%. Further, the top 5% PRS group reached a 6.69% lifetime absolute risk. Notably, this group reached the average population 10-year LUAD risk at age 50 (0.42%) by age 41, nine years earlier. CONCLUSIONS: Multi-ancestry PRS approaches enhance LUAD risk stratification in East Asian never-smokers, with consistent external validation, suggesting future clinical utility.", "classifications": [ { "id": "Hamamoto", "label": "Group Hamamoto", "parent": "Okamoto", "type": "group" }, { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Batel", "last_name": "Blechter", "name": null }, { "creator_type": "author", "first_name": "Xiaoyu", "last_name": "Wang", "name": null }, { "creator_type": "author", "first_name": "Juncheng", "last_name": "Dai", "name": null }, { "creator_type": "author", "first_name": "Christiana", "last_name": "Karsonaki", "name": null }, { "creator_type": "author", "first_name": "Jianxin", "last_name": "Shi", "name": null }, { "creator_type": "author", "first_name": "Kouya", "last_name": "Shiraishi", "name": null }, { "creator_type": "author", "first_name": "Jiyeon", "last_name": "Choi", "name": null }, { "creator_type": "author", "first_name": "Keitaro", "last_name": "Matsuo", "name": null }, { "creator_type": "author", "first_name": "Tzu-Yu", "last_name": "Chen", "name": null }, { "creator_type": "author", "first_name": "Rayjean J.", "last_name": "Hung", "name": null }, { "creator_type": "author", "first_name": "Kexin", "last_name": "Chen", "name": null }, { "creator_type": "author", "first_name": "Xiao-Ou", "last_name": "Shu", "name": null }, { "creator_type": "author", "first_name": "Young Tae", "last_name": "Kim", "name": null }, { "creator_type": "author", "first_name": "Parichoy Pal", "last_name": "Choudhury", "name": null }, { "creator_type": "author", "first_name": "Jacob", "last_name": "Williams", "name": null }, { "creator_type": "author", "first_name": "Maria Teresa", "last_name": "Landi", "name": null }, { "creator_type": "author", "first_name": "Dongxin", "last_name": "Lin", "name": null }, { "creator_type": "author", "first_name": "Wei", "last_name": "Zheng", "name": null }, { "creator_type": "author", "first_name": "Zhihua", "last_name": "Yin", "name": null }, { "creator_type": "author", "first_name": "Baosen", "last_name": "Zhou", "name": null }, { "creator_type": "author", "first_name": "Jiucun", "last_name": "Wang", "name": null }, { "creator_type": "author", "first_name": "Wei Jie", "last_name": "Seow", "name": null }, { "creator_type": "author", "first_name": "Lei", "last_name": "Song", "name": null }, { "creator_type": "author", "first_name": "I.-Shou", "last_name": "Chang", "name": null }, { "creator_type": "author", "first_name": "Wei", "last_name": "Hu", "name": null }, { "creator_type": "author", "first_name": "Li-Hsin", "last_name": "Chien", "name": null }, { "creator_type": "author", "first_name": "Qiuyin", "last_name": "Cai", "name": null }, { "creator_type": "author", "first_name": "Yun-Chul", "last_name": "Hong", "name": null }, { "creator_type": "author", "first_name": "Hee Nam", "last_name": "Kim", "name": null }, { "creator_type": "author", "first_name": "Yi-Long", "last_name": "Wu", "name": null }, { "creator_type": "author", "first_name": "Maria Pik", "last_name": "Wong", "name": null }, { "creator_type": "author", "first_name": "Brian Douglas", "last_name": "Richardson", "name": null }, { "creator_type": "author", "first_name": "Shilan", "last_name": "Li", "name": null }, { "creator_type": "author", "first_name": "Tongwu", "last_name": "Zhang", "name": null }, { "creator_type": "author", "first_name": "Charles", "last_name": "Breeze", "name": null }, { "creator_type": "author", "first_name": "Zhaoming", "last_name": "Wang", "name": null }, { "creator_type": "author", "first_name": "Bryan A.", "last_name": "Bassig", "name": null }, { "creator_type": "author", "first_name": "Jin Hee", "last_name": "Kim", "name": null }, { "creator_type": "author", "first_name": "Demetrius", "last_name": "Albanes", "name": null }, { "creator_type": "author", "first_name": "Jason Yy", "last_name": "Wong Sm", "name": null }, { "creator_type": "author", "first_name": "Min-Ho", "last_name": "Shin", "name": null }, { "creator_type": "author", "first_name": "Lap Ping", "last_name": "Chung", "name": null }, { "creator_type": "author", "first_name": "Yang", "last_name": "Yang", "name": null }, { "creator_type": "author", "first_name": "Hong", "last_name": "Zheng", "name": null }, { "creator_type": "author", "first_name": "Hongji", "last_name": "Dai", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null }, { "creator_type": "author", "first_name": "Xu-Chao", "last_name": "Zhang", "name": null }, { "creator_type": "author", "first_name": "Young-Chul", "last_name": "Kim", "name": null }, { "creator_type": "author", "first_name": "Neil E.", "last_name": "Caporaso", "name": null }, { "creator_type": "author", "first_name": "Jiang", "last_name": "Chang", "name": null }, { "creator_type": "author", "first_name": "James Chung Man", "last_name": "Ho", "name": null }, { "creator_type": "author", "first_name": "Yataro", "last_name": "Daigo", "name": null }, { "creator_type": "author", "first_name": "Yukihide", "last_name": "Momozawa", "name": null }, { "creator_type": "author", "first_name": "Yoichiro", "last_name": "Kamatani", "name": null }, { "creator_type": "author", "first_name": "Masashi", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Kenichi", "last_name": "Okubo", "name": null }, { "creator_type": "author", "first_name": "Takayuki", "last_name": "Honda", "name": null }, { "creator_type": "author", "first_name": "H. Dean", "last_name": "Hosgood", "name": null }, { "creator_type": "author", "first_name": "Hideo", "last_name": "Kunitoh", "name": null }, { "creator_type": "author", "first_name": "Shun-Ichi", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Yohei", "last_name": "Miyagi", "name": null }, { "creator_type": "author", "first_name": "Shingo", "last_name": "Matsumoto", "name": null }, { "creator_type": "author", "first_name": "Hidehito", "last_name": "Horinouchi", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Tsuboi", "name": null }, { "creator_type": "author", "first_name": "Ryuji", "last_name": "Hamamoto", "name": null }, { "creator_type": "author", "first_name": "Koichi", "last_name": "Goto", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Akiteru", "last_name": "Goto", "name": null }, { "creator_type": "author", "first_name": "Yoshihiro", "last_name": "Minamiya", "name": null }, { "creator_type": "author", "first_name": "Megumi", "last_name": "Hara", "name": null }, { "creator_type": "author", "first_name": "Yuichiro", "last_name": "Nishida", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Takeuchi", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Wakai", "name": null }, { "creator_type": "author", "first_name": "Koichi", "last_name": "Matsuda", "name": null }, { "creator_type": "author", "first_name": "Yoshinori", "last_name": "Murakami", "name": null }, { "creator_type": "author", "first_name": "Kimihiro", "last_name": "Shimizu", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Motonobu", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Yoichi", "last_name": "Ohtaki", "name": null }, { "creator_type": "author", "first_name": "Kazumi", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Tangchun", "last_name": "Wu", "name": null }, { "creator_type": "author", "first_name": "Fusheng", "last_name": "Wei", "name": null }, { "creator_type": "author", "first_name": "Mitchell J.", "last_name": "Machiela", "name": null }, { "creator_type": "author", "first_name": "Yeul Hong", "last_name": "Kim", "name": null }, { "creator_type": "author", "first_name": "In-Jae", "last_name": "Oh", "name": null }, { "creator_type": "author", "first_name": "Victor Ho Fun", "last_name": "Lee", "name": null }, { "creator_type": "author", "first_name": "Gee-Chen", "last_name": "Chang", "name": null }, { "creator_type": "author", "first_name": "Kuan-Yu", "last_name": "Chen", "name": null }, { "creator_type": "author", "first_name": "Wu-Chou", "last_name": "Su", "name": null }, { "creator_type": "author", "first_name": "Yuh-Min", "last_name": "Chen", "name": null }, { "creator_type": "author", "first_name": "Adeline", "last_name": "Seow", "name": null }, { "creator_type": "author", "first_name": "Jae Yong", "last_name": "Park", "name": null }, { "creator_type": "author", "first_name": "Sun-Seog", "last_name": "Kweon", "name": null }, { "creator_type": "author", "first_name": "Yu-Tang", "last_name": "Gao", "name": null }, { "creator_type": "author", "first_name": "Jianjun", "last_name": "Liu", "name": null }, { "creator_type": "author", "first_name": "Ann G.", "last_name": "Schwartz", "name": null }, { "creator_type": "author", "first_name": "Richard", "last_name": "Houlston", "name": null }, { "creator_type": "author", "first_name": "Ivan P.", "last_name": "Gorlov", "name": null }, { "creator_type": "author", "first_name": "Xifeng", "last_name": "Wu", "name": null }, { "creator_type": "author", "first_name": "Ping", "last_name": "Yang", "name": null }, { "creator_type": "author", "first_name": "Stephen", "last_name": "Lam", "name": null }, { "creator_type": "author", "first_name": "Adonina", "last_name": "Tardon", "name": null }, { "creator_type": "author", "first_name": "Chu", "last_name": "Chen", "name": null }, { "creator_type": "author", "first_name": "Stig E.", "last_name": "Bojesen", "name": null }, { "creator_type": "author", "first_name": "Mattias", "last_name": "Johansson", "name": null }, { "creator_type": "author", "first_name": "Angela", "last_name": "Risch", "name": null }, { "creator_type": "author", "first_name": "Heike", "last_name": "Bickeboller", "name": null }, { "creator_type": "author", "first_name": "Bu-Tian", "last_name": "Ji", "name": null }, { "creator_type": "author", "first_name": "H.-Erich", "last_name": "Wichmann", "name": null }, { "creator_type": "author", "first_name": "David C.", "last_name": "Christiani", "name": null }, { "creator_type": "author", "first_name": "Gad", "last_name": "Rennert", "name": null }, { "creator_type": "author", "first_name": "Susanne M.", "last_name": "Arnold", "name": null }, { "creator_type": "author", "first_name": "Paul", "last_name": "Brennan", "name": null }, { "creator_type": "author", "first_name": "James", "last_name": "McKay", "name": null }, { "creator_type": "author", "first_name": "John K.", "last_name": "Field", "name": null }, { "creator_type": "author", "first_name": "Michael P. A.", "last_name": "Davies", "name": null }, { "creator_type": "author", "first_name": "Sanjay S.", "last_name": "Shete", "name": null }, { "creator_type": "author", "first_name": "Loic", "last_name": "Le Marchand", "name": null }, { "creator_type": "author", "first_name": "Geoffrey", "last_name": "Liu", "name": null }, { "creator_type": "author", "first_name": "Angeline S.", "last_name": "Andrew", "name": null }, { "creator_type": "author", "first_name": "Lambertus A.", "last_name": "Kiemeney", "name": null }, { "creator_type": "author", "first_name": "Shan", "last_name": "Zienolddiny-Narui", "name": null }, { "creator_type": "author", "first_name": "Kjell", "last_name": "Grankvist", "name": null }, { "creator_type": "author", "first_name": "Angela", "last_name": "Cox", "name": null }, { "creator_type": "author", "first_name": "Fiona", "last_name": "Taylor", "name": null }, { "creator_type": "author", "first_name": "Jian-Min", "last_name": "Yuan", "name": null }, { "creator_type": "author", "first_name": "Philip", "last_name": "Lazarus", "name": null }, { "creator_type": "author", "first_name": "Matthew B.", "last_name": "Schabath", "name": null }, { "creator_type": "author", "first_name": "Melinda C.", "last_name": "Aldrich", "name": null }, { "creator_type": "author", "first_name": "Hyo-Sung", "last_name": "Jeon", "name": null }, { "creator_type": "author", "first_name": "Shih Sheng", "last_name": "Jiang", "name": null }, { "creator_type": "author", "first_name": "Chung-Hsing", "last_name": "Chen", "name": null }, { "creator_type": "author", "first_name": "Chin-Fu", "last_name": "Hsiao", "name": null }, { "creator_type": "author", "first_name": "Zhibin", "last_name": "Hu", "name": null }, { "creator_type": "author", "first_name": "Laura", "last_name": "Burdett", "name": null }, { "creator_type": "author", "first_name": "Meredith", "last_name": "Yeager", "name": null }, { "creator_type": "author", "first_name": "Amy", "last_name": "Hutchinson", "name": null }, { "creator_type": "author", "first_name": "Belynda", "last_name": "Hicks", "name": null }, { "creator_type": "author", "first_name": "Jia", "last_name": "Liu", "name": null }, { "creator_type": "author", "first_name": "Sonja I.", "last_name": "Berndt", "name": null }, { "creator_type": "author", "first_name": "Wei", "last_name": "Wu", "name": null }, { "creator_type": "author", "first_name": "Junwen", "last_name": "Wang", "name": null }, { "creator_type": "author", "first_name": "Yuqing", "last_name": "Li", "name": null }, { "creator_type": "author", "first_name": "Jin Eun", "last_name": "Choi", "name": null }, { "creator_type": "author", "first_name": "Kyong Hwa", "last_name": "Park", "name": null }, { "creator_type": "author", "first_name": "Sook Whan", "last_name": "Sung", "name": null }, { "creator_type": "author", "first_name": "Chang Hyun", "last_name": "Kang", "name": null }, { "creator_type": "author", "first_name": "Wen-Chang", "last_name": "Wang", "name": null }, { "creator_type": "author", "first_name": "Jun", "last_name": "Xu", "name": null }, { "creator_type": "author", "first_name": "Peng", "last_name": "Guan", "name": null }, { "creator_type": "author", "first_name": "Wen", "last_name": "Tan", "name": null }, { "creator_type": "author", "first_name": "Chong-Jen", "last_name": "Yu", "name": null }, { "creator_type": "author", "first_name": "Gong", "last_name": "Yang", "name": null }, { "creator_type": "author", "first_name": "Alan Dart Loon", "last_name": "Sihoe", "name": null }, { "creator_type": "author", "first_name": "Yi Young", "last_name": "Choi", "name": null }, { "creator_type": "author", "first_name": "In Kyu", "last_name": "Park", "name": null }, { "creator_type": "author", "first_name": "Hsiao-Han", "last_name": "Hung", "name": null }, { "creator_type": "author", "first_name": "Roel C. H.", "last_name": "Vermeulen", "name": null }, { "creator_type": "author", "first_name": "Iona", "last_name": "Cheng", "name": null }, { "creator_type": "author", "first_name": "Junjie", "last_name": "Wu", "name": null }, { "creator_type": "author", "first_name": "Fang-Yu", "last_name": "Tsai", "name": null }, { "creator_type": "author", "first_name": "John K. C.", "last_name": "Chan", "name": null }, { "creator_type": "author", "first_name": "Jihua", "last_name": "Li", "name": null }, { "creator_type": "author", "first_name": "Hsien-Chih", "last_name": "Lin", "name": null }, { "creator_type": "author", "first_name": "Jie", "last_name": "Liu", "name": null }, { "creator_type": "author", "first_name": "Bao", "last_name": "Song", "name": null }, { "creator_type": "author", "first_name": "Norie", "last_name": "Sawada", "name": null }, { "creator_type": "author", "first_name": "Taiki", "last_name": "Yamaji", "name": null }, { "creator_type": "author", "first_name": "Kathleen", "last_name": "Wyatt", "name": null }, { "creator_type": "author", "first_name": "Hongxia", "last_name": "Ma", "name": null }, { "creator_type": "author", "first_name": "Meng", "last_name": "Zhu", "name": null }, { "creator_type": "author", "first_name": "Yifan", "last_name": "Wang", "name": null }, { "creator_type": "author", "first_name": "Tianchen", "last_name": "Qi", "name": null }, { "creator_type": "author", "first_name": "Xuelian", "last_name": "Li", "name": null }, { "creator_type": "author", "first_name": "Yangwu", "last_name": "Ren", "name": null }, { "creator_type": "author", "first_name": "Ann", "last_name": "Chao", "name": null }, { "creator_type": "author", "first_name": "Motoki", "last_name": "Iwasaki", "name": null }, { "creator_type": "author", "first_name": "Junjie", "last_name": "Zhu", "name": null }, { "creator_type": "author", "first_name": "Guoping", "last_name": "Wu", "name": null }, { "creator_type": "author", "first_name": "Chih-Yi", "last_name": "Chen", "name": null }, { "creator_type": "author", "first_name": "Chien-Jen Chen", "last_name": "ScD", "name": null }, { "creator_type": "author", "first_name": "Pan-Chyr", "last_name": "Yang", "name": null }, { "creator_type": "author", "first_name": "Victoria L.", "last_name": "Stevens", "name": null }, { "creator_type": "author", "first_name": "Joseph F. Jr", "last_name": "Fraumeni", "name": null }, { "creator_type": "author", "first_name": "Kuang", "last_name": "Lin", "name": null }, { "creator_type": "author", "first_name": "Robin G.", "last_name": "Walters", "name": null }, { "creator_type": "author", "first_name": "Zhengming", "last_name": "Chen", "name": null }, { "creator_type": "author", "first_name": "Nilanjan", "last_name": "Chatterjee", "name": null }, { "creator_type": "author", "first_name": "Olga Y.", "last_name": "Gorlova", "name": null }, { "creator_type": "author", "first_name": "Christopher I.", "last_name": "Amos", "name": null }, { "creator_type": "author", "first_name": "Hongbing", "last_name": "Shen", "name": null }, { "creator_type": "author", "first_name": "Chao Agnes", "last_name": "Hsiung", "name": null }, { "creator_type": "author", "first_name": "Stephen J.", "last_name": "Chanock", "name": null }, { "creator_type": "author", "first_name": "Nathaniel", "last_name": "Rothman", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Kohno", "name": null }, { "creator_type": "author", "first_name": "Qing", "last_name": "Lan", "name": null }, { "creator_type": "author", "first_name": "Haoyu", "last_name": "Zhang", "name": null } ], "identifiers": { "doi": { "normalized": "10.1093/jnci/djaf272" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "41032288" } }, "mesh": [], "publication": { "conference_name": null, "date": "2025 Oct 1", "date_precision": "day", "issue": "", "normalized_date": "2025-10-01", "pages": "djaf272", "proceedings_title": null, "publisher": "", "title": "Journal of the National Cancer Institute", "volume": "", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Stratifying lung adenocarcinoma risk with multi-ancestry polygenic risk scores in East Asian never-smokers.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Covalent targeting of proteins with small molecule probes is a powerful approach for analyzing and manipulating biological functions. Recent advancements in the design of target selective covalent ligands further expand the scope of accessible proteins in this approach. Here we report beta-fluorovinylsulfonamide (FVS) as a versatile electrophile for the design of covalent ligands. FVS irreversibly reacts with cysteine residues in proteins to afford stable vinyl sulfide adducts. The reactivity of FVS is maintained with the introduction of various substituents at the beta-position, allowing for fine-tuning of the electrophilic reactivity and flexible molecular design of FVS-based covalent ligands. These reaction properties were leveraged in the development of highly selective covalent ligands for RSK2 and BTK. FVS compounds are also able to react with lysine residues in proteins to form enamine-type reversible covalent adducts, which are susceptible to hydrolysis under neutral aqueous conditions. This lysine reactivity of FVS led to the discovery of FVS compound 53 as a reversible covalent ligand for PFKL, which selectively reacts with K677 of PFKL and allosterically upregulates PFKL activity in living cells.", "classifications": [ { "id": "Nishida", "label": "Group Nishida", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Shunsuke", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Keisuke", "last_name": "Tokunaga", "name": null }, { "creator_type": "author", "first_name": "Yudai", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Yuya", "last_name": "Hirose", "name": null }, { "creator_type": "author", "first_name": "Emi", "last_name": "Mishiro-Sato", "name": null }, { "creator_type": "author", "first_name": "Keiko", "last_name": "Kano", "name": null }, { "creator_type": "author", "first_name": "Kaori", "last_name": "Sasaki-Tabata", "name": null }, { "creator_type": "author", "first_name": "Yuri", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Motohiro", "last_name": "Nishida", "name": null }, { "creator_type": "author", "first_name": "Naoya", "last_name": "Shindo", "name": null }, { "creator_type": "author", "first_name": "Akio", "last_name": "Ojida", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/jacs.5c07422" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "41034690" } }, "mesh": [ { "descriptor": "Agammaglobulinaemia Tyrosine Kinase", "descriptor_ui": "D000077329", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Ligands", "descriptor_ui": "D008024", "major_topic": false }, { "descriptor": "Molecular Structure", "descriptor_ui": "D015394", "major_topic": false }, { "descriptor": "Sulfonamides", "descriptor_ui": "D013449", "major_topic": true }, { "descriptor": "Vinyl Compounds", "descriptor_ui": "D014753", "major_topic": true } ], "publication": { "conference_name": null, "date": "2025 Oct 1", "date_precision": "day", "issue": "", "normalized_date": "2025-10-01", "pages": "", "proceedings_title": null, "publisher": "", "title": "Journal of the American Chemical Society", "volume": "", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "beta-Fluorovinylsulfonamide as a Highly Reactivity- and Structure-Tunable Electrophile for Covalent Targeting of Proteins.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Raman spectroscopy (RS) offers highly specific, label-free molecular identification, yet its application in deep-tissue imaging is fundamentally limited by light scattering and spectral interference from endogenous biomolecules. A promising strategy to mitigate these issues involves using vibrational tags that emit signals within the Raman-silent region (1800-2800 cm(-1)), minimizing background noise. However, these signals remain susceptible to attenuation due to the inherent optical opacity of biological tissues caused by refractive index (RI) mismatches among tissue constituents. Here, we introduce Clearing-enabled Light Enhancement for Analytical Raman in the Silent Region (Clear-SiR), a hybrid method that combines RI modulation through tissue clearing with spectral targeting in the silent region to enable high-fidelity Raman detection through biological tissue. Utilizing tartrazine, an FDA-approved dye with strong short-wavelength absorption, Clear-SiR homogenizes tissue RI based on the Kramers-Kronig relations, enhancing optical transparency and reducing light scattering. Paired with 4-aminobenzonitrile (4-ABN) as a nitrile-based silent region reporter, we demonstrate that Clear-SiR achieves up to a nearly 2-fold increase in detection depth under red (638 nm) and near-infrared (785 nm) excitation. We further use a rapid, gel-based tartrazine delivery protocol suitable for clinical and point-of-care settings. Our proof-of-concept results demonstrate that Clear-SiR overcomes both spectral and optical barriers for transcutaneous measurement, enabling highly accurate, deep-tissue biochemical sensing with minimal distraction from endogenous signals. By integration of physical tissue clearing with spectral targeting in the Raman-silent region, this method establishes a robust platform for probing molecular architecture at clinically relevant depths. Clear-SiR opens new avenues for noninvasive molecular phenotyping and longitudinal monitoring of pathophysiological process in organoids and intact tissues.", "classifications": [ { "id": "Fujita", "label": "Group Fujita", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Michael Ka Ho", "last_name": "Lee", "name": null }, { "creator_type": "author", "first_name": "Kenta", "last_name": "Mizushima", "name": null }, { "creator_type": "author", "first_name": "Peng", "last_name": "Zheng", "name": null }, { "creator_type": "author", "first_name": "Swati", "last_name": "Tanwar", "name": null }, { "creator_type": "author", "first_name": "Anoushka", "last_name": "Gupta", "name": null }, { "creator_type": "author", "first_name": "Katsumasa", "last_name": "Fujita", "name": null }, { "creator_type": "author", "first_name": "Ishan", "last_name": "Barman", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/acssensors.5c02046" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "41024637" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Refractometry", "descriptor_ui": "D012031", "major_topic": false }, { "descriptor": "Spectrum Analysis, Raman", "descriptor_ui": "D013059", "major_topic": true } ], "publication": { "conference_name": null, "date": "2025 Sep 30", "date_precision": "day", "issue": "", "normalized_date": "2025-09-30", "pages": "", "proceedings_title": null, "publisher": "", "title": "ACS sensors", "volume": "", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Spectrally Silent and Optically Transparent: Clear-SiR for Deep Raman Biomolecular Sensing.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Hirschsprung disease (HSCR) is a neurocristopathy, yet paradoxically, neural crest-derived EGCs are present within the muscle of the affected region. This study investigates the molecular identity, origins, and neurogenic potential of EGCs in the aganglionic mouse and human colon. We utilized single-cell RNA sequencing (scRNA-seq), immunohistochemistry, and in vitro culture of EGCs from aganglionic and ganglionated segments of Ednrb-null mice (Plp1-GFP;Baf-tdT;Ednrb(-/-)) and human HSCR tissues. Neurogenic potential and network formation were assessed, and the effects of glial cell line-derived neurotrophic factor (GDNF) on neurogenesis were evaluated. scRNA-seq and immunohistochemistry revealed the absence of GFAP+ intraganglionic (IG) glia in aganglionic colon, while CAMK2b+ extraganglionic (EG) glia and Schwann-like cells (SLCs) were present. EG glia exhibited a transcriptional profile similar to SLCs, suggesting a possible shared embryonic origin. EGCs in the aganglionic segment (comprising EGs and SLCs) exhibited reduced neurogenic potential and network complexity compared to EGCs from the ganglionated region (comprising EGs and IGs). GDNF partially restored neurogenic capacity and enhanced network complexity of EGCs isolated from the aganglionic segment, acting through a non-canonical NCAM1-dependent pathway independent of RET signaling.", "classifications": [ { "id": "Enomoto", "label": "Group Enomoto", "parent": "Enomoto", "type": "group" }, { "id": "Enomoto", "label": "Team Enomoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Jessica L.", "last_name": "Mueller", "name": null }, { "creator_type": "author", "first_name": "Chris", "last_name": "Han", "name": null }, { "creator_type": "author", "first_name": "Abigail", "last_name": "Leavitt", "name": null }, { "creator_type": "author", "first_name": "Vipin", "last_name": "Chauhan", "name": null }, { "creator_type": "author", "first_name": "Leah", "last_name": "Ott", "name": null }, { "creator_type": "author", "first_name": "Richard A.", "last_name": "Guyer", "name": null }, { "creator_type": "author", "first_name": "Toshihiro", "last_name": "Uesaka", "name": null }, { "creator_type": "author", "first_name": "Hideki", "last_name": "Enomoto", "name": null }, { "creator_type": "author", "first_name": "Lily", "last_name": "Cheng", "name": null }, { "creator_type": "author", "first_name": "Ryo", "last_name": "Hotta", "name": null }, { "creator_type": "author", "first_name": "Alan J.", "last_name": "Burns", "name": null }, { "creator_type": "author", "first_name": "Rhian", "last_name": "Stavely", "name": null }, { "creator_type": "author", "first_name": "Allan M.", "last_name": "Goldstein", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41598-025-17734-3" }, "pmcid": { "normalized": "PMC12474993" }, "pmid": { "normalized": "41006492" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "CD56 Antigen", "descriptor_ui": "D019002", "major_topic": true }, { "descriptor": "Colon", "descriptor_ui": "D003106", "major_topic": false }, { "descriptor": "Enteric Nervous System", "descriptor_ui": "D017615", "major_topic": false }, { "descriptor": "Glial Cell Line-Derived Neurotrophic Factor", "descriptor_ui": "D051100", "major_topic": true }, { "descriptor": "Hirschsprung Disease", "descriptor_ui": "D006627", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Neural Crest", "descriptor_ui": "D009432", "major_topic": false }, { "descriptor": "Neurogenesis", "descriptor_ui": "D055495", "major_topic": true }, { "descriptor": "Neuroglia", "descriptor_ui": "D009457", "major_topic": true }, { "descriptor": "Receptor, Endothelin B", "descriptor_ui": "D044023", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false } ], "publication": { "conference_name": null, "date": "2025 Sep 26", "date_precision": "day", "issue": "1", "normalized_date": "2025-09-26", "pages": "33200", "proceedings_title": null, "publisher": "", "title": "Scientific reports", "volume": "15", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Intramuscular enteric glia persist in Hirschsprung disease and undergo neurogenesis in response to GDNF-NCAM1 signaling.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: Deletion variants in mitochondrial DNA (mtDNA) are associated with various diseases, such as mitochondrial disorders and neurodegenerative diseases. Traditionally, mtDNA deletions have been studied using bulk DNA sequencing, but bulk methods average signals across cells, thereby masking the cell-type-specific mutational landscapes. Resolving mtDNA deletions at single-cell resolution is beneficial for understanding how these mutations affect distinct cell populations. To date, no specialized method exists for detecting cell-type-specific mtDNA deletions from single-cell RNA sequencing data. Notably, mtDNA possesses unique molecular features: a high copy number, stable transcription, and compact structure of the mitochondrial genome. This results in a relatively high abundance of mtDNA-derived reads even in single-cell RNA sequencing data, suggesting the possibility of detecting mtDNA deletion variants directly from transcriptomic data. RESULTS: Here, we present MitoDelta, a computational pipeline that enables the detection of mtDNA deletions at cell-type resolution solely from single-cell RNA sequencing data. MitoDelta combines a sensitive alignment strategy with robust statistical filtering based on a beta-binomial distribution model, allowing accurate identification of deletion events even from noisy single-cell transcriptomes. To capture cell-type-specific deletion patterns, MitoDelta analyzes reads pooled by annotated cell types, enabling quantification of deletion burden across distinct cellular populations. We benchmarked MitoDelta against existing mtDNA deletion detection tools and demonstrated superior overall performance. As a practical application, we applied MitoDelta to a published single-nucleus RNA sequencing dataset for Parkinson's disease and revealed distinct mtDNA deletion burdens across neuronal subtypes. CONCLUSIONS: MitoDelta enables the transcriptome-integrated, cell-type-specific detection of mtDNA deletions from single-cell RNA sequencing data alone, offering a valuable framework for reanalyzing public datasets and studying mitochondrial genome alterations at cell-type resolution. This integrated approach enables insights into how mtDNA deletions are distributed across specific cell types and cellular states, providing new opportunities to investigate the role of mtDNA deletions in cell-type-specific disease mechanisms. The tool is available at https://github.com/NikaidoLaboratory/mitodelta .", "classifications": [ { "id": "JPMJCR1926", "label": "JPMJCR1926", "researcher": "Hironobu Fujiwara", "type": "grant" }, { "id": "Fujiwara", "label": "Group Fujiwara", "parent": "Fujiwara", "type": "group" }, { "id": "Nikaido", "label": "Group Nikaido", "parent": "Fujiwara", "type": "group" }, { "id": "Fujiwara", "label": "Team Fujiwara", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Haruko", "last_name": "Nakagawa", "name": null }, { "creator_type": "author", "first_name": "Yasuyuki", "last_name": "Shima", "name": null }, { "creator_type": "author", "first_name": "Yohei", "last_name": "Sasagawa", "name": null }, { "creator_type": "author", "first_name": "Itoshi", "last_name": "Nikaido", "name": null } ], "identifiers": { "doi": { "normalized": "10.1186/s12864-025-11931-0" }, "pmcid": { "normalized": "PMC12465547" }, "pmid": { "normalized": "40999372" } }, "mesh": [ { "descriptor": "Computational Biology", "descriptor_ui": "D019295", "major_topic": true }, { "descriptor": "DNA, Mitochondrial", "descriptor_ui": "D004272", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Sequence Analysis, RNA", "descriptor_ui": "D017423", "major_topic": true }, { "descriptor": "Sequence Deletion", "descriptor_ui": "D017384", "major_topic": true }, { "descriptor": "Single-Cell Analysis", "descriptor_ui": "D059010", "major_topic": true }, { "descriptor": "Software", "descriptor_ui": "D012984", "major_topic": true } ], "publication": { "conference_name": null, "date": "2025 Sep 25", "date_precision": "day", "issue": "1", "normalized_date": "2025-09-25", "pages": "810", "proceedings_title": null, "publisher": "", "title": "BMC genomics", "volume": "26", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "MitoDelta: identifying mitochondrial DNA deletions at cell-type resolution from single-cell RNA sequencing data.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Half a century ago, it was discovered that in somatic plant cells actin microfilaments play a critical role in division plane orientation but not in cell plate assembly during cytokinesis. Because plant cytokinesis is brought about by the microtubule-based phragmoplast, the actomyosin system must be required for the centrifugally expanding phragmoplast to recognize the cortical division zone established by the microtubular preprophase band (PPB). It has been intriguing to learn how the two cytoskeletal elements communicate with each other in the two temporally separated cytokinetic apparatuses of the PPB and the phragmoplast. Half a century later, it is now clear that the PPB recruits the actomyosin system to the cortical division zone where the Myosin XI motors form macromolecular assemblies with Kinesin-12 motors and other microtubule-associated proteins. These Cytoskeleton-Associated Motor assemblies at the PPB site (CAMPs) play critical roles in the maintenance of the division site established by the PPB. They receive microtubules emanating from the edge of the expanding phragmoplast so that the developing cell plate can be inserted into the spatially defined position. Therefore, the actomyosin system joins microtubules to orchestrate the recognition of the PPB-defined position by the phragmoplast in order to execute cytokinesis in a spatiotemporally regulated manner in somatic plant cells.", "classifications": [ { "id": "JPMJCR2121", "label": "JPMJCR2121", "researcher": "Minako Ueda", "type": "grant" }, { "id": "Higaki", "label": "Group Higaki", "parent": "Ueda", "type": "group" }, { "id": "Ueda", "label": "Group Ueda", "parent": "Ueda", "type": "group" }, { "id": "Ueda", "label": "Team Ueda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Bo", "last_name": "Liu", "name": null }, { "creator_type": "author", "first_name": "Takumi", "last_name": "Higaki", "name": null }, { "creator_type": "author", "first_name": "Yuh-Ru", "last_name": "Julie Lee", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.pbi.2025.102790" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "40997652" } }, "mesh": [ { "descriptor": "Actomyosin", "descriptor_ui": "D000205", "major_topic": true }, { "descriptor": "Cytokinesis", "descriptor_ui": "D048749", "major_topic": true }, { "descriptor": "Microtubules", "descriptor_ui": "D008870", "major_topic": false }, { "descriptor": "Plant Cells", "descriptor_ui": "D059828", "major_topic": true }, { "descriptor": "Plants", "descriptor_ui": "D010944", "major_topic": true } ], "publication": { "conference_name": null, "date": "2025 Sep 24", "date_precision": "day", "issue": "", "normalized_date": "2025-09-24", "pages": "102790", "proceedings_title": null, "publisher": "", "title": "Current opinion in plant biology", "volume": "88", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Deciphering actomyosin functions in plant cytokinesis: A half-century odyssey.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Periodontal ligament stem cell (PDLSC)-based therapy has emerged as a promising approach to regenerate damaged periodontal tissue in periodontitis treatments. To advance the application of this therapy, a nondestructive method to monitor osteogenic differentiation and evaluate the osteogenic abilities of PDLSCs is essential. In this study, we developed a rapid extended-focus Raman imaging technique for the label-free evaluation of cell differentiation. The developed technique enabled the high-throughput acquisition of Raman spectra of the whole cell volume, facilitating the monitoring of osteogenic differentiation of PDLSCs lineages with low and high osteogenic abilities. Using multivariate analysis of Raman spectra, we identified extracellular matrix (ECM) components represented by collagen type I as key contributors to the spectral differences between two cell populations. Combining Raman imaging and fluorescence observation, we confirmed the correlation between ECM deposition and hydroxyapatite (HA) generation, which indicated that ECM accumulation reflects the osteogenic ability of PDLSCs. These findings highlight the application of the extended-focus Raman imaging approach to realize the label-free assessment of PDLSC lineages with distinct osteogenic capabilities, paving the way to nondestructive cell screening in periodontal tissue regeneration treatment.", "classifications": [ { "id": "Fujita", "label": "Group Fujita", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Heqi", "last_name": "Xi", "name": null }, { "creator_type": "author", "first_name": "Phan", "last_name": "Bhongsatiern", "name": null }, { "creator_type": "author", "first_name": "Menglu", "last_name": "Li", "name": null }, { "creator_type": "author", "first_name": "Tomoaki", "last_name": "Iwayama", "name": null }, { "creator_type": "author", "first_name": "Masahide", "last_name": "Takedachi", "name": null }, { "creator_type": "author", "first_name": "Yoshinori", "last_name": "Yamaguchi", "name": null }, { "creator_type": "author", "first_name": "Katsumasa", "last_name": "Fujita", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/acs.analchem.5c00921" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "40994110" } }, "mesh": [ { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": true }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Durapatite", "descriptor_ui": "D017886", "major_topic": false }, { "descriptor": "Extracellular Matrix", "descriptor_ui": "D005109", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Osteogenesis", "descriptor_ui": "D010012", "major_topic": true }, { "descriptor": "Periodontal Ligament", "descriptor_ui": "D010513", "major_topic": true }, { "descriptor": "Spectrum Analysis, Raman", "descriptor_ui": "D013059", "major_topic": true }, { "descriptor": "Stem Cells", "descriptor_ui": "D013234", "major_topic": true } ], "publication": { "conference_name": null, "date": "2025 Sep 24", "date_precision": "day", "issue": "", "normalized_date": "2025-09-24", "pages": "", "proceedings_title": null, "publisher": "", "title": "Analytical chemistry", "volume": "", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Label-Free Evaluation of Osteogenic Differentiation Using Extended-Focus Raman Imaging.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Microtubules are cytoskeletal filaments that self-assemble from the protein tubulin, a heterodimer of alpha-tubulin and beta-tubulin, and are important for cell mechanics, migration, and division. Much work has focused on how the nucleotide state of beta-tubulin regulates the structure and dynamics of microtubules. In contrast, less is known about the structure and function of the C-terminal tails (CTTs) of alpha- and beta-tubulin which are thought to freely protrude from the surface of the microtubule. To study the CTTs, we developed three different biosensors that bind the tyrosinated alpha-tubulin CTT (Y-alphaCTT) on the microtubule lattice. Surprisingly, live imaging of the probes indicates that the Y-alphaCTT is not accessible under normal cellular conditions. Lattice binding of the Y-alphaCTT probes can be increased by three different ways of changing the tubulin conformational state: the drug Taxol, expression of microtubule-associated proteins (MAPs) that recognize or promote an expanded tubulin conformation, or expression of tubulin that cannot hydrolyze GTP. Molecular dynamics simulations indicate that the Y-alphaCTT undergoes numerous transient interactions with the bodies of alpha-tubulin and beta-tubulin in the lattice, and that the frequency of these interactions is regulated by the tubulin nucleotide state. These findings suggest that accessibility of the Y-alphaCTT is governed by local nucleotide- and MAP-dependent conformational changes to tubulin subunits within the microtubule lattice.", "classifications": [ { "id": "Higaki", "label": "Group Higaki", "parent": "Ueda", "type": "group" }, { "id": "Ueda", "label": "Team Ueda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Takashi", "last_name": "Hotta", "name": null }, { "creator_type": "author", "first_name": "Morgan L.", "last_name": "Pimm", "name": null }, { "creator_type": "author", "first_name": "Ezekiel C.", "last_name": "Thomas", "name": null }, { "creator_type": "author", "first_name": "Yang", "last_name": "Yue", "name": null }, { "creator_type": "author", "first_name": "Patrick", "last_name": "DeLear", "name": null }, { "creator_type": "author", "first_name": "Lynne", "last_name": "Blasius", "name": null }, { "creator_type": "author", "first_name": "Michael", "last_name": "Cianfrocco", "name": null }, { "creator_type": "author", "first_name": "Morgan", "last_name": "DeSantis", "name": null }, { "creator_type": "author", "first_name": "Ryota", "last_name": "Horiuchi", "name": null }, { "creator_type": "author", "first_name": "Takumi", "last_name": "Higaki", "name": null }, { "creator_type": "author", "first_name": "David", "last_name": "Sept", "name": null }, { "creator_type": "author", "first_name": "Ryoma", "last_name": "Ohi", "name": null }, { "creator_type": "author", "first_name": "Kristen J.", "last_name": "Verhey", "name": null } ], "identifiers": { "doi": { "normalized": "10.1101/2025.09.23.678010" }, "pmcid": { "normalized": null }, "pmid": { "normalized": null } }, "mesh": [], "publication": { "conference_name": null, "date": "2025 Sep 23", "date_precision": "day", "issue": null, "normalized_date": "2025-09-23", "pages": null, "proceedings_title": null, "publisher": null, "title": null, "volume": null, "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Accessibility of the unstructured alpha-tubulin C-terminal tail is controlled by microtubule lattice conformation.", "url": "", "zotero": { "item_type": "preprint" } }, { "abstract": "BACKGROUND: Lung cancer (LC) survivors have a 4-6-fold higher risk of developing a second primary LC than the general population. In prospective multicenter studies, 15-17 % of patients undergoing surgical resection for LC develop a second malignancy, often in the lung, with risk persisting beyond 5 years. We characterized its incidence and risk factors, including genetic mutations, in a large retrospective cohort. METHODS: This study retrospectively analyzed 5,274 patients undergoing complete resection for non-small cell lung cancer at the National Cancer Center Hospital Tokyo between 2011 and 2023. Second primary LCs were identified using the Martini and Melamed criteria. We estimated cumulative incidence with the Fine-Gray competing-risk method, treating death as a competing event, and calculated sub-distribution hazard ratios (SHRs). RESULTS: The median follow-up was 4.4 years (range: 0-12). Overall, 365 (6.9 %) patients developed a second primary LC at a median interval of 4.1 years. Cumulative incidence from surgery was 0.7 % at 1 year, 6.1 % at 5 years, and 15.1 % at 10 years. Multivariate analysis identified heavy smoking history ([SHR]: 1.47, 95 % confidence interval [CI]: 1.07-2.30, p = 0.02), first status of multiple primary lung cancer (MPLC), defined as >/= 2 synchronous tumors at baseline (SHR: 1.88, 95 % CI: 1.25-2.85, p = 0.002), and higher consolidation-to-tumor ratio (CTR) (SHR: 2.40, 95 % CI: 1.67-3.47, p < 0.001) as independent risk factors. Among 1,292 (24.5 %) patients assessed for genetic mutations, 699 (13.2 %) harbored at least one clinically targetable driver mutation; however, mutation status did not affect risk of second primary LC (p = 0.46). CONCLUSIONS: Heavy smoking history, first status of MPLC, and higher CTR increase the risk of second primary LC; mutation status does not. Patients with these features require intensified, long-term surveillance.", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Chihiro", "last_name": "Takemura", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Yukihiro", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Ryoko", "last_name": "Inaba Higashiyama", "name": null }, { "creator_type": "author", "first_name": "Hidehito", "last_name": "Horinouchi", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Igaki", "name": null }, { "creator_type": "author", "first_name": "Noboru", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null }, { "creator_type": "author", "first_name": "Shun-Ichi", "last_name": "Watanabe", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.lungcan.2025.108750" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "40986990" } }, "mesh": [ { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Aged, 80 and over", "descriptor_ui": "D000369", "major_topic": false }, { "descriptor": "Carcinoma, Non-Small-Cell Lung", "descriptor_ui": "D002289", "major_topic": true }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Follow-Up Studies", "descriptor_ui": "D005500", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Incidence", "descriptor_ui": "D015994", "major_topic": false }, { "descriptor": "Lung Neoplasms", "descriptor_ui": "D008175", "major_topic": true }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": false }, { "descriptor": "Neoplasms, Second Primary", "descriptor_ui": "D016609", "major_topic": true }, { "descriptor": "Retrospective Studies", "descriptor_ui": "D012189", "major_topic": false }, { "descriptor": "Risk Factors", "descriptor_ui": "D012307", "major_topic": false } ], "publication": { "conference_name": null, "date": "2025 Sep 20", "date_precision": "day", "issue": "", "normalized_date": "2025-09-20", "pages": "108750", "proceedings_title": null, "publisher": "", "title": "Lung cancer (Amsterdam, Netherlands)", "volume": "208", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Unveiling the molecular and clinical risk landscape of second primary lung cancer in resected non-small cell lung cancer.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Parental care is fundamental to the physical and mental well-being of mammalian offspring. Females undergo pregnancy, parturition, and lactation, with hormones pivotal to these processes-such as estrogen, prolactin, and oxytocin-also playing essential roles in mediating infant-directed caregiving behaviors. Although the extent of paternal involvement varies widely across species, the same hormones that regulate maternal transitions may be utilized to facilitate paternal behavioral adaptations. Recent advances in single-cell transcriptomics and cell-type-specific genetic manipulations have elucidated the mechanisms through which hormones interact with discrete cell types to drive structural and physiological plasticity within key regions of the brain governing parental behaviors. Furthermore, parental care serves as a valuable model for studying naturally occurring motivated behavioral learning, wherein higher-order cognitive regions and monoaminergic systems play an integrative role. This review highlights recent progress in this field, with a brief discussion on the potential sexually dimorphic engagement of specific hormonal systems.", "classifications": [ { "id": "Miyamichi", "label": "Group Miyamichi", "parent": "Enomoto", "type": "group" }, { "id": "Enomoto", "label": "Team Enomoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Kazunari", "last_name": "Miyamichi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.conb.2025.103113" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "40972155" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Behavior, Animal", "descriptor_ui": "D001522", "major_topic": true }, { "descriptor": "Brain", "descriptor_ui": "D001921", "major_topic": true }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Maternal Behavior", "descriptor_ui": "D008425", "major_topic": true }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Paternal Behavior", "descriptor_ui": "D010332", "major_topic": true }, { "descriptor": "Sex Characteristics", "descriptor_ui": "D012727", "major_topic": false } ], "publication": { "conference_name": null, "date": "2025 Sep 18", "date_precision": "day", "issue": "", "normalized_date": "2025-09-18", "pages": "103113", "proceedings_title": null, "publisher": "", "title": "Current opinion in neurobiology", "volume": "95", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Neural basis for parental behavioral transitions in mice.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: Radiotherapy is a well-established cancer treatment, but its detrimental effects on normal tissue have been significantly underestimated. Late radiation-induced tissue damage leads to dysfunctions like loss of elasticity and delayed wound healing, which negatively affect the prognosis and quality of life of cancer survivors. Our previous research demonstrated that local prophylactic administration of adipose-derived stem cells (ASCs) immediately after irradiation could prevent late radiation-related disorders. This study aims to explore the effects of systemic administration of ASCs for future clinical applications. METHODS: Nude mice were irradiated on their dorsal skin (40 Gy total: 2 Gy x 20, simulating clinical radiotherapy). Human ASCs were administered systemically (via intravenous or intraperitoneal injection, once or twice). Control groups included a non-irradiated group and a vehicle-treated radiotherapy group. After 6 months, full-thickness skin wounds were created on the mice's dorsal skin and observed for 28 days. The wound healing process was assessed, and tissue samples were analyzed using immunohistochemistry. RESULTS: Radiotherapy caused subcutaneous fat atrophy and fibrosis at 6 months, which was effectively prevented in the ASC-treated groups. Wound healing was faster in the ASC-treated groups than in the vehicle-treated groups, though not as fast as in the No-radiotherapy group. ASC-treated groups exhibited less fat layer atrophy and fibrosis than vehicle-treated groups. Engraftment of ASCs was confirmed in the fatty layer of the irradiated skin. CONCLUSIONS: Prophylactic systemic administration of ASCs immediately after radiotherapy can prevent tissue damage and dysfunction associated with radiation therapy.", "classifications": [ { "id": "Kuchimaru", "label": "Group Kuchimaru", "parent": "Shintaku", "type": "group" }, { "id": "Shintaku", "label": "Team Shintaku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yoshihiro", "last_name": "Toyohara", "name": null }, { "creator_type": "author", "first_name": "Yoshihiro", "last_name": "Sowa", "name": null }, { "creator_type": "author", "first_name": "Natsumi", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Takako", "last_name": "Shirado", "name": null }, { "creator_type": "author", "first_name": "Bihang", "last_name": "Zhang", "name": null }, { "creator_type": "author", "first_name": "Sangchul", "last_name": "Hyun", "name": null }, { "creator_type": "author", "first_name": "Shino", "last_name": "Higai", "name": null }, { "creator_type": "author", "first_name": "Bolun", "last_name": "Li", "name": null }, { "creator_type": "author", "first_name": "Takahiro", "last_name": "Kuchimaru", "name": null }, { "creator_type": "author", "first_name": "Kotaro", "last_name": "Yoshimura", "name": null } ], "identifiers": { "doi": { "normalized": "10.1097/prs.0000000000012449" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "40957110" } }, "mesh": [ { "descriptor": "Adipose Tissue", "descriptor_ui": "D000273", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Nude", "descriptor_ui": "D008819", "major_topic": false }, { "descriptor": "Radiation Injuries", "descriptor_ui": "D011832", "major_topic": true }, { "descriptor": "Radiation Injuries, Experimental", "descriptor_ui": "D011833", "major_topic": true }, { "descriptor": "Radiotherapy", "descriptor_ui": "D011878", "major_topic": false }, { "descriptor": "Skin", "descriptor_ui": "D012867", "major_topic": false }, { "descriptor": "Stem Cell Transplantation", "descriptor_ui": "D033581", "major_topic": true }, { "descriptor": "Wound Healing", "descriptor_ui": "D014945", "major_topic": false } ], "publication": { "conference_name": null, "date": "2025 Sep 16", "date_precision": "day", "issue": "", "normalized_date": "2025-09-16", "pages": "", "proceedings_title": null, "publisher": "", "title": "Plastic and reconstructive surgery", "volume": "", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Systemic Administration of Adipose-Derived Stem Cells Immediately After Radiotherapy to Prevent development of Late Radiation-Induced Damage.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Despite advances in androgen receptor signaling inhibitors (ARSIs) and poly (ADP-ribose) polymerase inhibitors (PARPIs), metastatic castration-resistant prostate cancer (mCRPC) remains lethal. PARPIs clinical efficacy is limited in patients with homologous recombination repair deficiencies, such as BRCA1/2 mutations, due to resistance. Thus, identifying novel synthetic lethal interactions with PARP may expand treatment options and improve therapeutic efficacy. Here, to identify genes that influence sensitivity to the PARPI olaparib, we conducted a genome-wide CRISPR-Cas9 knockout screening of 18,010 genes in DU145, 22Rv1, and LNCaP prostate cancer cell lines. Our screening identified PARP and LIG1 as synthetic lethality-inducing factors, whereas TP53 conferred resistance to PARPIs. Simultaneous inhibition of LIG1 and PARP increased DNA damage and apoptosis. Additionally, the combination of the LIG1 inhibitor L82-G17 with olaparib exhibited synergistic effects. To the best of our knowledge, we validated this combination therapy in vivo for the first time, suppressing tumor growth in a DU145 xenograft model while minimizing toxicity in normal tissues. Immunohistochemical analysis revealed that LIG1 was overexpressed in CRPC tissues, suggesting its potential as a therapeutic target. This study established LIG1 as a novel synthetic lethality-inducing factor in prostate cancer, showing that L82-G17 enhances the efficacy of olaparib, regardless of the BRCA mutation status. These findings suggest that the combination of PARP and LIG1 inhibitors could be a novel therapeutic strategy for mCRPC.", "classifications": [ { "id": "Yusa", "label": "Group Yusa", "parent": "Eiraku", "type": "group" }, { "id": "Eiraku", "label": "Team Eiraku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Masaru", "last_name": "Tani", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Hatano", "name": null }, { "creator_type": "author", "first_name": "Yu", "last_name": "Ishizuya", "name": null }, { "creator_type": "author", "first_name": "Toshiki", "last_name": "Oka", "name": null }, { "creator_type": "author", "first_name": "Tomohiro", "last_name": "Kanaki", "name": null }, { "creator_type": "author", "first_name": "Shunsuke", "last_name": "Inoguchi", "name": null }, { "creator_type": "author", "first_name": "Akihiro", "last_name": "Yoshimura", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Horibe", "name": null }, { "creator_type": "author", "first_name": "Yutong", "last_name": "Liu", "name": null }, { "creator_type": "author", "first_name": "Sassi", "last_name": "Nesrine", "name": null }, { "creator_type": "author", "first_name": "Yohei", "last_name": "Okuda", "name": null }, { "creator_type": "author", "first_name": "Akinaru", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Toshihiro", "last_name": "Uemura", "name": null }, { "creator_type": "author", "first_name": "Gaku", "last_name": "Yamamichi", "name": null }, { "creator_type": "author", "first_name": "Takuji", "last_name": "Hayashi", "name": null }, { "creator_type": "author", "first_name": "Yoshiyuki", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Taigo", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Atsunari", "last_name": "Kawashima", "name": null }, { "creator_type": "author", "first_name": "Takao", "last_name": "Yamaguchi", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Obika", "name": null }, { "creator_type": "author", "first_name": "Kosuke", "last_name": "Yusa", "name": null }, { "creator_type": "author", "first_name": "Norio", "last_name": "Nonomura", "name": null }, { "creator_type": "author", "first_name": "Keisuke", "last_name": "Nimura", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/cas.70194" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "40957713" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Antineoplastic Combined Chemotherapy Protocols", "descriptor_ui": "D000971", "major_topic": true }, { "descriptor": "Apoptosis", "descriptor_ui": "D017209", "major_topic": false }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "CRISPR-Cas Systems", "descriptor_ui": "D064113", "major_topic": false }, { "descriptor": "DNA Damage", "descriptor_ui": "D004249", "major_topic": false }, { "descriptor": "DNA Ligase ATP", "descriptor_ui": "D000072481", "major_topic": true }, { "descriptor": "Drug Resistance, Neoplasm", "descriptor_ui": "D019008", "major_topic": false }, { "descriptor": "Drug Synergism", "descriptor_ui": "D004357", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Nude", "descriptor_ui": "D008819", "major_topic": false }, { "descriptor": "Phthalazines", "descriptor_ui": "D010793", "major_topic": false }, { "descriptor": "Piperazines", "descriptor_ui": "D010879", "major_topic": false }, { "descriptor": "Poly(ADP-ribose) Polymerase Inhibitors", "descriptor_ui": "D000067856", "major_topic": true }, { "descriptor": "Prostatic Neoplasms", "descriptor_ui": "D011471", "major_topic": true }, { "descriptor": "Prostatic Neoplasms, Castration-Resistant", "descriptor_ui": "D064129", "major_topic": true }, { "descriptor": "Synthetic Lethal Mutations", "descriptor_ui": "D000072020", "major_topic": true }, { "descriptor": "Tumor Suppressor Protein p53", "descriptor_ui": "D016159", "major_topic": false }, { "descriptor": "Xenograft Model Antitumor Assays", "descriptor_ui": "D023041", "major_topic": false } ], "publication": { "conference_name": null, "date": "2025 Sep 16", "date_precision": "day", "issue": "", "normalized_date": "2025-09-16", "pages": "", "proceedings_title": null, "publisher": "", "title": "Cancer science", "volume": "", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Development of a Synthetic Lethality-Based Combination Therapy Using LIG1 and PARP Inhibitors for Prostate Cancer.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "AIM: Biliary tract cancers, including intrahepatic cholangiocarcinoma (ICC), are aggressive with limited treatment options and poor prognosis. Recent trials (TOPAZ-1, Keynote-966) showed improved survival with ICIs plus gemcitabine and cisplatin. Targeted therapies, including FGFR inhibitors, are promising for cholangiocarcinoma patients with FGFR2 gene fusions or rearrangements, although few reports exist on FGFR2 positivity and clinical data in Asia. This study aims to address this gap by evaluating FGFR2 fusions or rearrangements in intrahepatic and perihilar cholangiocarcinoma patients across Asia, providing insights into their clinical significance and potential therapeutic implications. METHODS: This multicenter study evaluated the frequency of FGFR2 rearrangements and fusion genes in ICC and perihilar cholangiocarcinoma across Asia (Thailand, Malaysia, Vietnam, and Taiwan) using fluorescence in situ hybridization (FISH) and comprehensive genomic profiling with the Todai OncoPanel2 (TOP2). RESULTS: Of 113 patients, 102 were eligible; FGFR2 rearrangements/fusions were found in 3.9% (4 cases) by FISH, all of which were also confirmed by the TOP2 panel, consistent with the Japanese PRELUDE study. Younger age was significantly associated with FGFR2 positivity (34.5 +/- 3.17 vs. 62.69 +/- 1.04; p = 0.0003), whereas no correlation was observed with hepatitis infection, alcohol use, or smoking history. Genomic profiling identified frequent mutations in TP53, KRAS, and ARID1A with notable regional variability. Patients treated with ICIs showed significantly longer progression-free survival compared to other therapies: ICI + cytotoxic (348 days, 95% CI: 0-897), platinum-based + GEM (240 days, 95% CI: 197-282), and other treatments (168 days, 95% CI: 11-325; p = 0.017). CONCLUSION: The FGFR2 positivity rate in Asia is slightly lower but consistent with Japanese reports and is more common in younger patients with ICC. Distinct genetic alterations may characterize Asian populations.", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yuta", "last_name": "Maruki", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null }, { "creator_type": "author", "first_name": "Chiharu", "last_name": "Mizoguchi", "name": null }, { "creator_type": "author", "first_name": "Kathleen Yasmin", "last_name": "de Almeida", "name": null }, { "creator_type": "author", "first_name": "Aumkhae", "last_name": "Sookprasert", "name": null }, { "creator_type": "author", "first_name": "Charuwan", "last_name": "Akewanlop", "name": null }, { "creator_type": "author", "first_name": "Ming-Huang", "last_name": "Chen", "name": null }, { "creator_type": "author", "first_name": "Ekaphop", "last_name": "Sirachainan", "name": null }, { "creator_type": "author", "first_name": "Dao Van", "last_name": "Tu", "name": null }, { "creator_type": "author", "first_name": "Rozita Abdul", "last_name": "Malik", "name": null }, { "creator_type": "author", "first_name": "Chaiyut", "last_name": "Charoentum", "name": null }, { "creator_type": "author", "first_name": "Hwoei Fen Soo", "last_name": "Hoo", "name": null }, { "creator_type": "author", "first_name": "Suhana", "last_name": "Yusak", "name": null }, { "creator_type": "author", "first_name": "Tsung-Hao", "last_name": "Liu", "name": null }, { "creator_type": "author", "first_name": "Rangasamy", "last_name": "Ramachandran", "name": null }, { "creator_type": "author", "first_name": "Patrapim", "last_name": "Sunpaweravong", "name": null }, { "creator_type": "author", "first_name": "Pei Jye", "last_name": "Voon", "name": null }, { "creator_type": "author", "first_name": "Najihah Abu", "last_name": "Bakar", "name": null }, { "creator_type": "author", "first_name": "Junki", "last_name": "Mizusawa", "name": null }, { "creator_type": "author", "first_name": "Hitomi Sumiyoshi", "last_name": "Okuma", "name": null }, { "creator_type": "author", "first_name": "Kenichi", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Chigusa", "last_name": "Morizane", "name": null }, { "creator_type": "author", "first_name": "Takuji", "last_name": "Okusaka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/hepr.70031" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "40958387" } }, "mesh": [], "publication": { "conference_name": null, "date": "2025 Sep 16", "date_precision": "day", "issue": "", "normalized_date": "2025-09-16", "pages": "", "proceedings_title": null, "publisher": "", "title": "Hepatology research : the official journal of the Japan Society of Hepatology", "volume": "", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "FGFR2 Fusions or Rearrangements in Young Intrahepatic and Perihilar Cholangiocarcinoma Patients: Key Genetic Insights From a Pan-Asian Study.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Hydrogen selenide (H(2)Se) is an important metabolite in selenium biochemistry and plays a crucial role in redox biology. While its significance has become increasingly recognized, research on H(2)Se is challenging due to its instability and high reactivity. Suitable compounds (aka donors) that can selectively produce H(2)Se in biological systems would facilitate this research field. In this work, we explored photo-triggered H(2)Se donors by utilizing two structural templates: 2-nitrobenzyl selenides and 2-methoxy-6-naphthacyl selenides. The photoreactions of these compounds under light were studied. 2-Nitrobenzyl selenides were found to release H(2)Se (and its oxidized form H(2)Se(2)) slowly under UV light, but the released H(2)Se/H(2)Se(2) could further react with the photoproduct and be consumed. On the other hand, naphthacyl selenides could undergo clean and fast reactions to produce H(2)Se/H(2)Se(2), as well as a stable and fluorescent photoproduct. This self-monitoring and quick releasing ability make naphthacyl selenides ‛smart donors' for biological applications. Importantly, this donor was found to induce protein S-selenylation (CysS-SeH) on Cys47 and Cys91 in both recombinant peroxiredoxin-6 (PRDX6) and PRDX6-overexpressing HEK293T cells. This photo-triggered donor system may serve as a new strategy to control selenium-based protein post-translational modifications for mechanistic studies into selenium metabolic pathways and ferroptosis.", "classifications": [ { "id": "JPMJCR2024", "label": "JPMJCR2024", "researcher": "Motohiro Nishida", "type": "grant" }, { "id": "Akaike", "label": "Group Akaike", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Group Nishida", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Biswajit", "last_name": "Roy", "name": null }, { "creator_type": "author", "first_name": "Eshani", "last_name": "Das", "name": null }, { "creator_type": "author", "first_name": "Meg", "last_name": "Shieh", "name": null }, { "creator_type": "author", "first_name": "Seiryo", "last_name": "Ogata", "name": null }, { "creator_type": "author", "first_name": "Minkyung", "last_name": "Jung", "name": null }, { "creator_type": "author", "first_name": "Hiroaki", "last_name": "Fujita", "name": null }, { "creator_type": "author", "first_name": "Sen", "last_name": "Zhang", "name": null }, { "creator_type": "author", "first_name": "Jerome R.", "last_name": "Robinson", "name": null }, { "creator_type": "author", "first_name": "Takaaki", "last_name": "Akaike", "name": null }, { "creator_type": "author", "first_name": "Ming", "last_name": "Xian", "name": null } ], "identifiers": { "doi": { "normalized": "10.1039/d5sc05141j" }, "pmcid": { "normalized": "PMC12452010" }, "pmid": { "normalized": "40988687" } }, "mesh": [], "publication": { "conference_name": null, "date": "2025 Sep 15", "date_precision": "day", "issue": "", "normalized_date": "2025-09-15", "pages": "", "proceedings_title": null, "publisher": "", "title": "Chemical science", "volume": "", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Light responsive hydrogen selenide (H(2)Se)/hydrogen diselenide (H(2)Se(2)) donors: applied for protein S-selenylation on PRDX6.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Cystathionine gamma-lyase (CSE) is a pyridoxal 5'-phosphate (PLP)-dependent enzyme that catalyzes the final step of the transsulfuration pathway, converting cystathionine into cysteine. Additionally, CSE is also essential for the formation of cysteine hydropolysulfide (Cys-S-(S)n-H), known as supersulfides, by metabolizing cystine under pathological conditions. We previously reported that, during cystine metabolism, CSE undergoes self-inactivation through polysulfidation at the Cys136 residue. Here, contrary to the anticipated role of L-S-nitrosocysteine (L-CysNO) as a nitric oxide (NO) donor, we demonstrate that it serves as a substrate for CSE and that its metabolites inhibit the activity of the enzyme during L-CysNO metabolism. The in vitro incubation of CSE-but not the Cys136/171Val mutant-with L-CysNO resulted in the dose-dependent inhibition of supersulfide production, which was not reversed by the reducing agents. Notably, CSE activity remained unchanged upon preincubation with other NO donors, such as S-nitrosoglutathione or D-CysNO, but was inhibited when coincubated with cysteine. Furthermore, when PLP was removed from the CSE/L-CysNO premix, L-CysNO no longer inhibited CSE activity, suggesting that CSE metabolizes L-CysNO and that its metabolites contribute to enzyme inactivation. Indeed, we identified thionitrous acid and pyruvate as the primary CSE/L-CysNO reaction products. Thus, we establish L-CysNO as a CSE substrate and demonstrate that its metabolites act as enzyme inhibitors through a novel irreversible modification at the Cys136/171 residues.", "classifications": [ { "id": "JPMJCR2024", "label": "JPMJCR2024", "researcher": "Motohiro Nishida", "type": "grant" }, { "id": "Akaike", "label": "Group Akaike", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Group Nishida", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Shoma", "last_name": "Araki", "name": null }, { "creator_type": "author", "first_name": "Tsuyoshi", "last_name": "Takata", "name": null }, { "creator_type": "author", "first_name": "Sunghyeon", "last_name": "Yoon", "name": null }, { "creator_type": "author", "first_name": "Shingo", "last_name": "Kasamatsu", "name": null }, { "creator_type": "author", "first_name": "Hideshi", "last_name": "Ihara", "name": null }, { "creator_type": "author", "first_name": "Hidehiko", "last_name": "Nakagawa", "name": null }, { "creator_type": "author", "first_name": "Takaaki", "last_name": "Akaike", "name": null }, { "creator_type": "author", "first_name": "Yukihiro", "last_name": "Tsuchiya", "name": null }, { "creator_type": "author", "first_name": "Yasuo", "last_name": "Watanabe", "name": null } ], "identifiers": { "doi": { "normalized": "10.3390/antiox14091113" }, "pmcid": { "normalized": "PMC12466479" }, "pmid": { "normalized": "41009017" } }, "mesh": [], "publication": { "conference_name": null, "date": "2025 Sep 13", "date_precision": "day", "issue": "9", "normalized_date": "2025-09-13", "pages": "", "proceedings_title": null, "publisher": "", "title": "Antioxidants (Basel, Switzerland)", "volume": "14", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "The Supersulfide-Producing Activity of Rat Cystathionine gamma-Lyase Is Irreversibly Inactivated by L-CysNO but Not by L-GSNO.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Brown adipose tissue (BAT) plays a pivotal role in energy expenditure and metabolic health, yet the influence of specific sugars like fructose on brown adipocyte development remains poorly understood. Here, we employ high-speed line-illumination Raman imaging, combined with machine learning, to investigate how varying sugar environments - fructose, glucose, or both - impact the differentiation of human brown preadipocytes (HBPs). This label-free, non-destructive method provides spatially-resolved insight into lipid content, composition, and subcellular distribution during adipogenesis. Quantitative ratiometric analysis of Raman spectra reveals that fructose exposure leads to higher lipid unsaturation and esterification, indicative of impaired differentiation. Trajectory inference and unsupervised clustering further identify distinct subpopulations of adipocytes, demonstrating that fructose-treated cells exhibit phenotypes associated with early differentiation stages. Together, our findings reveal a negative regulatory role of fructose in brown adipocyte maturation and highlight Raman imaging as a powerful tool for dissecting metabolic cell states under variable nutrient conditions.", "classifications": [ { "id": "Fujita", "label": "Group Fujita", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Anoushka", "last_name": "Gupta", "name": null }, { "creator_type": "author", "first_name": "Pooja", "last_name": "Anantha", "name": null }, { "creator_type": "author", "first_name": "Hidenori", "last_name": "Koresawa", "name": null }, { "creator_type": "author", "first_name": "Heqi", "last_name": "Xi", "name": null }, { "creator_type": "author", "first_name": "Yu-Hua Beckham", "last_name": "Yang", "name": null }, { "creator_type": "author", "first_name": "Michael Ka Ho", "last_name": "Lee", "name": null }, { "creator_type": "author", "first_name": "Katsumasa", "last_name": "Fujita", "name": null }, { "creator_type": "author", "first_name": "Sui-Seng", "last_name": "Tee", "name": null }, { "creator_type": "author", "first_name": "Ishan", "last_name": "Barman", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.bios.2025.117994" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "40957282" } }, "mesh": [ { "descriptor": "Adipocytes, Brown", "descriptor_ui": "D052437", "major_topic": true }, { "descriptor": "Adipogenesis", "descriptor_ui": "D050156", "major_topic": true }, { "descriptor": "Adipose Tissue, Brown", "descriptor_ui": "D002001", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Fructose", "descriptor_ui": "D005632", "major_topic": true }, { "descriptor": "Glucose", "descriptor_ui": "D005947", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Single-Cell Analysis", "descriptor_ui": "D059010", "major_topic": true }, { "descriptor": "Spectrum Analysis, Raman", "descriptor_ui": "D013059", "major_topic": true } ], "publication": { "conference_name": null, "date": "2025 Sep 13", "date_precision": "day", "issue": "", "normalized_date": "2025-09-13", "pages": "117994", "proceedings_title": null, "publisher": "", "title": "Biosensors & bioelectronics", "volume": "290", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Single-cell Raman imaging reveals fructose impairs brown adipocyte differentiation.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Multiplexed fluid control is a demanding task in various studies in life sciences and bioengineering. Herein, we present open-source microfluidic sequence automation (MiSA) that offers flexible and multiplexed fluid control for various applications, providing constant flow via pressure-based feedback control with 10-plex capability and pulsed flow on the order of 100 ms. MiSA was self-contained, including a pressure source, and employed an Arduino Micro to integrate ten solenoid valves, an off-the-shelf pressure regulator, and a flow sensor to balance cost and reliability. To offer stable microflow control, especially at a low flow rate under low flow resistance, MiSA used a potentiometer that tuned the range of the pressure control by leveraging the full 8-bit output from the Arduino Micro applied to the pressure regulator. We demonstrated the practical use of MiSA for multiplexed chemical reactions by performing hybridization-based in situ sequencing. To demonstrate the flexibility of MiSA, we showed the extensions of our system for two pressure regulations under open-loop control in flow rate by revealing three independent applications: droplet generation, microfluidic spinning of spider silk fiber, and atomization of protein solution. We envision that this open source will offer resources for researchers to explore microfluidic applications rapidly with an affordable investment.", "classifications": [ { "id": "Shintaku", "label": "Group Shintaku", "parent": "Shintaku", "type": "group" }, { "id": "Shintaku", "label": "Team Shintaku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Junichi", "last_name": "Murai", "name": null }, { "creator_type": "author", "first_name": "Mahmoud N.", "last_name": "Abdelmoez", "name": null }, { "creator_type": "author", "first_name": "Keisuke", "last_name": "Kondo", "name": null }, { "creator_type": "author", "first_name": "Kohei", "last_name": "Takamuro", "name": null }, { "creator_type": "author", "first_name": "Keiji", "last_name": "Nozaki", "name": null }, { "creator_type": "author", "first_name": "Tim", "last_name": "Schiller", "name": null }, { "creator_type": "author", "first_name": "Thomas R.", "last_name": "Scheibel", "name": null }, { "creator_type": "author", "first_name": "Keiji", "last_name": "Numata", "name": null }, { "creator_type": "author", "first_name": "Hisano", "last_name": "Yajima", "name": null }, { "creator_type": "author", "first_name": "Kanako Terakado", "last_name": "Kimura", "name": null }, { "creator_type": "author", "first_name": "Takao", "last_name": "Hashiguchi", "name": null }, { "creator_type": "author", "first_name": "Taikopaul", "last_name": "Kaneko", "name": null }, { "creator_type": "author", "first_name": "Misa", "last_name": "Minegishi", "name": null }, { "creator_type": "author", "first_name": "Hirofumi", "last_name": "Shintaku", "name": null } ], "identifiers": { "doi": { "normalized": "10.1039/d5lc00551e" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "40899717" } }, "mesh": [ { "descriptor": "Automation", "descriptor_ui": "D001331", "major_topic": true }, { "descriptor": "Equipment Design", "descriptor_ui": "D004867", "major_topic": false }, { "descriptor": "Lab-On-A-Chip Devices", "descriptor_ui": "D056656", "major_topic": true }, { "descriptor": "Microfluidic Analytical Techniques", "descriptor_ui": "D046210", "major_topic": true } ], "publication": { "conference_name": null, "date": "2025 Sep 3", "date_precision": "day", "issue": "", "normalized_date": "2025-09-03", "pages": "", "proceedings_title": null, "publisher": "", "title": "Lab on a chip", "volume": "", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "An open source for multiplexed, stable and transient flows to advance life sciences using microfluidic control automation.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The basement membrane (BM), a specialized extracellular matrix (ECM), provides structural support for epithelial, endothelial, and other parenchymal cells. Once considered a static scaffold, the BM is now recognized as a dynamic and complex nanostructure composed of a diversity of molecules that actively regulate cell behavior and tissue organization. Its molecular composition, assembly, and remodeling are precisely controlled in a tissue- and stage-specific manner, contributing to the regulation of local and global mechanical properties and biochemical signaling. Understanding BM structure and function requires integrated approaches across biological scales-from nanoscale molecular interactions to tissue-level architecture. In this review, we highlight advances in three methodological areas: (1) imaging techniques that reveal BM nanostructure and dynamics, (2) manipulation strategies that uncover causal roles of BM components, and (3) omics-based approaches that map BM composition and cellular sources. Integrating these strategies enables the bridging of molecular events and organ-level functions, offering new insights into how the BM is involved in development, homeostasis, and disease progression. The aim of this review is to provide researchers with a comprehensive perspective on evolving tools for dissecting BM structure, dynamics, and function.", "classifications": [ { "id": "Fujiwara", "label": "Group Fujiwara", "parent": "Fujiwara", "type": "group" }, { "id": "Fujiwara", "label": "Team Fujiwara", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Kohei", "last_name": "Omachi", "name": null }, { "creator_type": "author", "first_name": "Hironobu", "last_name": "Fujiwara", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.matbio.2025.09.001" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "40907838" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Basement Membrane", "descriptor_ui": "D001485", "major_topic": true }, { "descriptor": "Extracellular Matrix", "descriptor_ui": "D005109", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Molecular Imaging", "descriptor_ui": "D057054", "major_topic": true } ], "publication": { "conference_name": null, "date": "2025 Sep 2", "date_precision": "day", "issue": "", "normalized_date": "2025-09-02", "pages": "S0945-053X(25)00081-2", "proceedings_title": null, "publisher": "", "title": "Matrix biology : journal of the International Society for Matrix Biology", "volume": "", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Exploring Basement Membrane Dynamics through Cross-Scale Imaging, Manipulation, and Molecular Mapping.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Background/Objectives: HER2, a critical diagnostic marker and therapeutic target in breast cancer, is a membrane receptor that forms diverse signaling complexes, the constituents of which have not been fully characterized in actual breast cancer tissues. Methods: In this study, we applied the Rapid Immunoprecipitation Mass Spectrometry of Endogenous Proteins (RIME) method, originally developed to explore transcription factor complexes, to identify the complexes formed by HER2 in HER2-positive breast cancer specimens. Results: Through our approach, we successfully identified multiple complex components, including MARCKS, a novel HER2-interacting partner, which we verified using both proximal ligation assay in cultured cells and immunohistochemistry in tissue sections. TCGA analysis further revealed that high MARCKS expression significantly correlates with ER negativity, as confirmed by multivariate analysis, suggesting its potential role as a prognostic indicator in aggressive breast cancer subtypes. Conclusions: These results demonstrate the capability of RIME to elucidate interactomes of membrane proteins such as HER2 in clinical tissue specimens. Furthermore, this study highlights its broader applicability beyond nuclear proteins, underscoring its potential for discovering novel prognostic and diagnostic clinical markers in diverse cancer types.", "classifications": [ { "id": "Suzuki", "label": "Group Suzuki", "parent": "Takekawa", "type": "group" }, { "id": "Takekawa", "label": "Team Takekawa", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Atsushi", "last_name": "Yokoyama", "name": null }, { "creator_type": "author", "first_name": "Shun", "last_name": "Sawatsubashi", "name": null }, { "creator_type": "author", "first_name": "Akiko", "last_name": "Ebata", "name": null }, { "creator_type": "author", "first_name": "Yasuhiro", "last_name": "Miki", "name": null }, { "creator_type": "author", "first_name": "Yuri", "last_name": "Otsubo", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Suzuki", "name": null } ], "identifiers": { "doi": { "normalized": "10.3390/cancers17172882" }, "pmcid": { "normalized": "PMC12428157" }, "pmid": { "normalized": "40940979" } }, "mesh": [], "publication": { "conference_name": null, "date": "2025 Sep 2", "date_precision": "day", "issue": "17", "normalized_date": "2025-09-02", "pages": "", "proceedings_title": null, "publisher": "", "title": "Cancers", "volume": "17", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "HER2 Interactome Profiling Reveals MARCKS as a Candidate Marker Associated with Aggressive Breast Cancer.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Although anaplastic thyroid carcinomas (ATCs) typically arise from papillary thyroid carcinomas (PTCs), follicular thyroid carcinomas (FTCs) can also progress to ATCs; however, histologically confirmed FTC-derived ATCs are relatively uncommon and remain poorly characterized. To clarify this phenomenon, we analyzed eight FTC-derived ATCs and compared them with 11 PTC-derived ATCs. Whole-exome sequencing (WES) was conducted on the differentiated thyroid carcinoma (DTC) and ATC components within the same tumors to examine mutational profiles; three additional cases underwent FoundationOne(R) testing. The demographic features were similar between FTC- and PTC-derived ATCs. Histologically, spindle-cell morphology was more common in FTC-derived ATCs (3/8), whereas PTC-derived ATCs exhibited squamoid (5/11) and giant cell features (5/11), including osteoclast-like cells. WES was successfully performed on both the ATC and FTC components in seven of the eight FTC-derived ATCs. Common alterations included TERT promoter (5/7), NRAS (4/7), and HRAS (2/7) mutations in both components. TP53 mutations were observed only in the ATC component (5/7). EIF1AX mutations co-occurred with TERT and HRAS mutations in two cases. PTEN mutations were found in two FTCs with solid/trabecular patterns but were absent in the corresponding ATC components. One tumor harbored a DGCR8 p.E518K mutation that was retained during progression. By contrast, PTC-derived ATCs consistently showed concurrent BRAF and TERT promoter mutations (11/11). Immunohistochemistry for BRAF V600E, RAS Q61R, p53, PTEN, and MTAP showed high concordance with the corresponding mutation status. These findings revealed significant histological and genetic differences between FTC- and PTC-derived ATCs, providing new insights into the molecular basis of FTC dedifferentiation into ATC.", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Toru", "last_name": "Odate", "name": null }, { "creator_type": "author", "first_name": "Tetsuo", "last_name": "Kondo", "name": null }, { "creator_type": "author", "first_name": "Ryohei", "last_name": "Katoh", "name": null }, { "creator_type": "author", "first_name": "Koichi", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Toshihide", "last_name": "Ueno", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null }, { "creator_type": "author", "first_name": "Taisuke", "last_name": "Mori", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/s12022-025-09875-y" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "40887557" } }, "mesh": [ { "descriptor": "Adenocarcinoma, Follicular", "descriptor_ui": "D018263", "major_topic": true }, { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Aged, 80 and over", "descriptor_ui": "D000369", "major_topic": false }, { "descriptor": "Disease Progression", "descriptor_ui": "D018450", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": false }, { "descriptor": "Thyroid Cancer, Papillary", "descriptor_ui": "D000077273", "major_topic": true }, { "descriptor": "Thyroid Carcinoma, Anaplastic", "descriptor_ui": "D065646", "major_topic": true }, { "descriptor": "Thyroid Neoplasms", "descriptor_ui": "D013964", "major_topic": true } ], "publication": { "conference_name": null, "date": "2025 Sep 1", "date_precision": "day", "issue": "1", "normalized_date": "2025-09-01", "pages": "30", "proceedings_title": null, "publisher": "", "title": "Endocrine pathology", "volume": "36", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Progression of Follicular Thyroid Carcinomas to Anaplastic Thyroid Carcinomas: Molecular and Clinicopathologic Characteristics with Comparison to Papillary Thyroid Carcinoma-Derived Anaplastic Thyroid Carcinomas.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: Although vaccination has significantly contributed to controlling the coronavirus disease 2019 (COVID-19) infections, a high risk of side effects has resulted in vaccination hesitancy. Nevertheless, as COVID-19 has become common but still has a severe impact on vulnerable people, we might need to follow a long-term vaccination routine. Therefore, elucidating the characteristics of individuals who may exhibit either vulnerability or resilience to the side effects associated with COVID-19 vaccinations is of the utmost importance for the vaccination plan against COVID-19. METHODS: Self-reported data on demographics, physical health, addictive lifestyle habits, mental health, and side effects were collected online. For 998 participants who received two vaccination doses, we performed repeated measures ANOVA, including side effects scores as dependent variables and individual characteristics as independent variables. RESULTS: We found interactions between vaccine dose and history of suspected lifestyle diseases (F = 4.460, p = 0.012) or trait anxiety (F = 5.548, p = 0.019). Besides the aggregation of side effects after the second dose compared to the first dose, we found that increased side effects after vaccination were associated with specific personal factors: younger age (F = 18.973, p = 0.000), female sex (F = 34.507, p = 0.000), low BMI (F = 4.205, p = 0.015), no history of \"specific health guidance\" (F = 5.004, p = 0.007) or smoking (F = 9.123, p = 0.003) or drinking (F = 3.335, p = 0.036), and higher levels of depressive symptoms (F = 15.134, p = 0.000) or trait anxiety (F = 26.350, p = 0.000). CONCLUSION: Physical characteristics and lifestyle habits linked with intact immune function enhanced side effects, whereas psychological characteristics linked with impaired immune function also enhanced side effects. These seemingly contradictory results could be explained at least partly by nocebo effects and suggest the need for psychological support for people with high levels of depressive symptoms or trait anxiety. Furthermore, interaction results imply that such support might be especially beneficial to those who are young and unaffected by lifestyle diseases while simultaneously showing high trait anxiety.", "classifications": [ { "id": "Fujiwara", "label": "Group Fujiwara", "parent": "Fujiwara", "type": "group" }, { "id": "Fujiwara", "label": "Team Fujiwara", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Kosuke", "last_name": "Tsurumi", "name": null }, { "creator_type": "author", "first_name": "Hironobu", "last_name": "Fujiwara", "name": null }, { "creator_type": "author", "first_name": "Teruhisa", "last_name": "Uwatoko", "name": null }, { "creator_type": "author", "first_name": "Toshiya", "last_name": "Murai", "name": null } ], "identifiers": { "doi": { "normalized": "10.1186/s40359-025-03325-4" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "40890884" } }, "mesh": [ { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Age Factors", "descriptor_ui": "D000367", "major_topic": false }, { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Anxiety", "descriptor_ui": "D001007", "major_topic": false }, { "descriptor": "COVID-19", "descriptor_ui": "D000086382", "major_topic": true }, { "descriptor": "COVID-19 Vaccines", "descriptor_ui": "D000086663", "major_topic": true }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Japan", "descriptor_ui": "D007564", "major_topic": false }, { "descriptor": "Life Style", "descriptor_ui": "D008019", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "SARS-CoV-2", "descriptor_ui": "D000086402", "major_topic": false }, { "descriptor": "Vaccination", "descriptor_ui": "D014611", "major_topic": true }, { "descriptor": "Vaccination Hesitancy", "descriptor_ui": "D000088823", "major_topic": false }, { "descriptor": "Young Adult", "descriptor_ui": "D055815", "major_topic": false } ], "publication": { "conference_name": null, "date": "2025 Sep 1", "date_precision": "day", "issue": "1", "normalized_date": "2025-09-01", "pages": "995", "proceedings_title": null, "publisher": "", "title": "BMC psychology", "volume": "13", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Dissociable impacts of physical and psychological factors on side effects after COVID-19 vaccination in Japan: A within-subject repeated measures design.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Chronic kidney disease (CKD) is a life-threatening condition, and constipation is a progressive risk factor. We evaluated changes in uremic toxins, renal function, and the safety of lubiprostone, a selective chloride channel activator, in patients with CKD. In this phase 2, randomized, double-blind, placebo-controlled trial across nine centers in Japan, 150 patients with stage IIIb-IV CKD received lubiprostone (8 or 16 micrograms) or placebo for 24 weeks. The primary end point was change in indoxyl sulfate levels. Secondary end points included other uremic toxins and renal function markers. Lubiprostone did not alter uremic toxin levels but improved or preserved estimated glomerular filtration rate and its slope in the 16-microgram group. Mild-to-moderate gastrointestinal events occurred in the placebo and 16-microgram groups. Multiomics analysis revealed that lubiprostone modulated the gut microbial agmatine pathway and increased spermidine levels, thereby improving renal mitochondrial function. Lubiprostone is a previously unknown and safe therapeutic option to mitigate renal decline in CKD.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Shun", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Masaaki", "last_name": "Nakayama", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Yokoo", "name": null }, { "creator_type": "author", "first_name": "Satoru", "last_name": "Sanada", "name": null }, { "creator_type": "author", "first_name": "Yoshifumi", "last_name": "Ubara", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Komatsuda", "name": null }, { "creator_type": "author", "first_name": "Katsuhiko", "last_name": "Asanuma", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Tsuneo", "last_name": "Konta", "name": null }, { "creator_type": "author", "first_name": "Junichiro J.", "last_name": "Kazama", "name": null }, { "creator_type": "author", "first_name": "Takehiro", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Shinji", "last_name": "Fukuda", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Takuji", "last_name": "Yamada", "name": null }, { "creator_type": "author", "first_name": "Sayaka", "last_name": "Mizutani", "name": null }, { "creator_type": "author", "first_name": "Mitsuharu", "last_name": "Matsumoto", "name": null }, { "creator_type": "author", "first_name": "Yuji", "last_name": "Naito", "name": null }, { "creator_type": "author", "first_name": "Kensei", "last_name": "Taguchi", "name": null }, { "creator_type": "author", "first_name": "Kei", "last_name": "Fukami", "name": null }, { "creator_type": "author", "first_name": "Hitomi", "last_name": "Kashiwagi", "name": null }, { "creator_type": "author", "first_name": "Koichi", "last_name": "Kikuchi", "name": null }, { "creator_type": "author", "first_name": "Chitose", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Hidetaka", "last_name": "Tokuno", "name": null }, { "creator_type": "author", "first_name": "Marina", "last_name": "Urasato", "name": null }, { "creator_type": "author", "first_name": "Ryota", "last_name": "Kujirai", "name": null }, { "creator_type": "author", "first_name": "Yotaro", "last_name": "Matsumoto", "name": null }, { "creator_type": "author", "first_name": "Yasutoshi", "last_name": "Akiyama", "name": null }, { "creator_type": "author", "first_name": "Yoshihisa", "last_name": "Tomioka", "name": null }, { "creator_type": "author", "first_name": "Shun", "last_name": "Itai", "name": null }, { "creator_type": "author", "first_name": "Yoshiyasu", "last_name": "Tongu", "name": null }, { "creator_type": "author", "first_name": "Eikan", "last_name": "Mishima", "name": null }, { "creator_type": "author", "first_name": "Chiharu", "last_name": "Kawabe", "name": null }, { "creator_type": "author", "first_name": "Tomoko", "last_name": "Kasahara", "name": null }, { "creator_type": "author", "first_name": "Yoshiaki", "last_name": "Ogata", "name": null }, { "creator_type": "author", "first_name": "Takafumi", "last_name": "Toyohara", "name": null }, { "creator_type": "author", "first_name": "Takeya", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Tetsuhiro", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Takaaki", "last_name": "Abe", "name": null } ], "identifiers": { "doi": { "normalized": "10.1126/sciadv.adw3934" }, "pmcid": { "normalized": "PMC12396341" }, "pmid": { "normalized": "40880481" } }, "mesh": [ { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Double-Blind Method", "descriptor_ui": "D004311", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Glomerular Filtration Rate", "descriptor_ui": "D005919", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Lubiprostone", "descriptor_ui": "D000068238", "major_topic": true }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Mitochondria", "descriptor_ui": "D008928", "major_topic": true }, { "descriptor": "Polyamines", "descriptor_ui": "D011073", "major_topic": true }, { "descriptor": "Renal Insufficiency, Chronic", "descriptor_ui": "D051436", "major_topic": true } ], "publication": { "conference_name": null, "date": "2025 Aug 29", "date_precision": "day", "issue": "35", "normalized_date": "2025-08-29", "pages": "eadw3934", "proceedings_title": null, "publisher": "", "title": "Science advances", "volume": "11", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Lubiprostone in chronic kidney disease: Insights into mitochondrial function and polyamines from a randomized phase 2 clinical trial.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "NUTM1-rearranged (NUTM1-R) infant acute lymphoblastic leukaemia (ALL) is a newly identified subgroup of non-KMT2A-R infant ALL, with ACIN1::NUTM1 the most frequent fusion. KMT2A-R and NUTM1-R infant ALL are characterized by fewer copy number alterations. Moreover, the gene expression profile in NUTM1-R infant ALL characteristically reveals upregulation of the genes that are involved in KMT2A-R infant ALL development, including HOXA9 and HOXA10. However, the direct association of NUTM1-fusion with this gene expression remains unexplored. Clinically, in sharp contrast to KMT2A-R infant ALL, the prognosis of NUTM1-R infant ALL is excellent, although its drug sensitivity profile remains unclear. Here, we newly identified an ACIN1::NUTM1-positive ALL cell line, KOPN32, which was previously established from a relapsed infant-ALL case, as the only cell line with NUTM1-fusion. KOPN32 had fewer copy number alterations, like KMT2A-R ALL cell lines. Both KOPN32 and an ACIN1::NUTM1-inducible ALL model, which was established using the ACIN1::NUTM1 fusion cDNA subcloned from KOPN32, revealed upregulation of HOXA9, HOXA10, SKIDA1 and BMI1, indicating direct involvement of ACIN1::NUTM1 fusion in the upregulation of these genes. In the drug sensitivity to eight standard agents, KOPN32 showed high sensitivity to both daunorubicin and vincristine; both are crucial agents in the induction therapy for infant ALL.", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Minori", "last_name": "Tamai", "name": null }, { "creator_type": "author", "first_name": "Chiaki", "last_name": "Komatsu", "name": null }, { "creator_type": "author", "first_name": "Keiko", "last_name": "Kagami", "name": null }, { "creator_type": "author", "first_name": "Shin", "last_name": "Kasai", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Koshi", "last_name": "Akahane", "name": null }, { "creator_type": "author", "first_name": "Kumiko", "last_name": "Goi", "name": null }, { "creator_type": "author", "first_name": "Chihiro", "last_name": "Tomoyasu", "name": null }, { "creator_type": "author", "first_name": "Toshihiko", "last_name": "Imamura", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Oguri", "name": null }, { "creator_type": "author", "first_name": "Sumio", "last_name": "Iwasaki", "name": null }, { "creator_type": "author", "first_name": "Takanori", "last_name": "Teshima", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Inukai", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/bjh.70130" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "40884014" } }, "mesh": [ { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Gene Expression Profiling", "descriptor_ui": "D020869", "major_topic": false }, { "descriptor": "Gene Expression Regulation, Leukemic", "descriptor_ui": "D015973", "major_topic": true }, { "descriptor": "Homeodomain Proteins", "descriptor_ui": "D018398", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Infant", "descriptor_ui": "D007223", "major_topic": false }, { "descriptor": "Neoplasm Proteins", "descriptor_ui": "D009363", "major_topic": true }, { "descriptor": "Nuclear Proteins", "descriptor_ui": "D009687", "major_topic": true }, { "descriptor": "Oncogene Proteins, Fusion", "descriptor_ui": "D015514", "major_topic": true }, { "descriptor": "Precursor Cell Lymphoblastic Leukemia-Lymphoma", "descriptor_ui": "D054198", "major_topic": true }, { "descriptor": "Transcriptome", "descriptor_ui": "D059467", "major_topic": true } ], "publication": { "conference_name": null, "date": "2025 Aug 29", "date_precision": "day", "issue": "", "normalized_date": "2025-08-29", "pages": "", "proceedings_title": null, "publisher": "", "title": "British journal of haematology", "volume": "", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "A characteristic gene expression profile regulated by ACIN1::NUTM1 fusion in a newly identified infant leukaemic cell line and an ACIN1::NUTM1-inducible model.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The hair cycle is a valuable model for studying tissue remodeling processes in adult mammals. Time course single-cell transcriptomics offers a powerful approach for characterizing changes in cellular states and interactions; however, its application in human tissues remains challenging. Here, we performed single-cell RNA sequencing on 19 human skin tissues, each containing a single hair follicle. We reconstructed a pseudotemporal progression of the hair cycle-termed the \"pseudo-hair cycle\"-by computationally ordering samples according to their gene expression profiles. The pseudo-hair cycle delineates the continuum of gene expression changes occurring in 16 distinct epithelial and dermal cell populations throughout the hair cycle, revealing specific cellular states and interactions. We identified hair follicle keratinocytes, dermal sheath fibroblasts, vascular endothelial cells, and leukocytes as key contributors to tissue remodeling during catagen. Our study provides a high-resolution temporal dataset for investigating the dynamic molecular and cellular mechanisms underlying skin remodeling in humans.", "classifications": [ { "id": "Fujiwara", "label": "Group Fujiwara", "parent": "Fujiwara", "type": "group" }, { "id": "Fujiwara", "label": "Team Fujiwara", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Jun", "last_name": "Yokota", "name": null }, { "creator_type": "author", "first_name": "Takamasa", "last_name": "Gomi", "name": null }, { "creator_type": "author", "first_name": "Yasuko", "last_name": "Harada", "name": null }, { "creator_type": "author", "first_name": "Kazuyuki", "last_name": "Yo", "name": null }, { "creator_type": "author", "first_name": "Kyungmin", "last_name": "Ahn", "name": null }, { "creator_type": "author", "first_name": "Noriko", "last_name": "Sanzen", "name": null }, { "creator_type": "author", "first_name": "Hiroki", "last_name": "Machida", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Shirai", "name": null }, { "creator_type": "author", "first_name": "Hironobu", "last_name": "Fujiwara", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.celrep.2025.116196" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "40884793" } }, "mesh": [ { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Fibroblasts", "descriptor_ui": "D005347", "major_topic": false }, { "descriptor": "Gene Expression Profiling", "descriptor_ui": "D020869", "major_topic": false }, { "descriptor": "Hair", "descriptor_ui": "D006197", "major_topic": true }, { "descriptor": "Hair Follicle", "descriptor_ui": "D018859", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Keratinocytes", "descriptor_ui": "D015603", "major_topic": false }, { "descriptor": "Single-Cell Analysis", "descriptor_ui": "D059010", "major_topic": true }, { "descriptor": "Skin", "descriptor_ui": "D012867", "major_topic": true }, { "descriptor": "Transcriptome", "descriptor_ui": "D059467", "major_topic": true } ], "publication": { "conference_name": null, "date": "2025 Aug 28", "date_precision": "day", "issue": "9", "normalized_date": "2025-08-28", "pages": "116196", "proceedings_title": null, "publisher": "", "title": "Cell reports", "volume": "44", "year": 2025 }, "ssbd": { "database": [], "repository": [ "ssbd-repos-000427" ] }, "title": "Single-cell transcriptomic reconstruction of the human hair cycle: Capturing the temporal dynamics of skin tissue remodeling.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Prostate cancer is one of the most common malignancies in men and remodeling of extracellular collagen, especially collagen type I immensely contributes to the progress of prostate cancer. Discoidin domain receptor 2 (DDR2) is a receptor of collagen type I and transmits intracellular signaling in not only normal cells but also malignant cells, facilitating tumor progression. However, clinical and biological significance of DDR2 has not been well examined in prostate cancer. We therefore immunolocalized DDR2 and collagen type I in 117 prostate carcinoma tissues and correlated their immunoreactivity with clinicopathological characteristics of prostate cancer. We also conducted in vitro experiments using human prostate cancer cell lines to confirm the findings from immunohistochemical study. DDR2 immunoreactivity was positively associated with an aggressive phenotype of prostate cancer, partially in association with dense collagen I tissues which consisted of thin fibers. In addition, DDR2 immunoreactivity was significantly correlated with adverse clinical outcomes of prostate cancer. In vitro experiments revealed that DDR2 promoted proliferation and migration of PC-3 and DU-145 prostate cancer cell lines. It is therefore speculated that DDR2 promoted prostate cancer progression by interacting with collagen I, serving as a potent prognostic factor in prostate cancer.", "classifications": [ { "id": "Suzuki", "label": "Group Suzuki", "parent": "Takekawa", "type": "group" }, { "id": "Takekawa", "label": "Team Takekawa", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Mikoto", "last_name": "Sagehashi", "name": null }, { "creator_type": "author", "first_name": "Kiyoshi", "last_name": "Takagi", "name": null }, { "creator_type": "author", "first_name": "Ai", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Mio", "last_name": "Yamaguchi-Tanaka", "name": null }, { "creator_type": "author", "first_name": "Yasuhiro", "last_name": "Miki", "name": null }, { "creator_type": "author", "first_name": "Akihiro", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Suzuki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1267/ahc.25-00009" }, "pmcid": { "normalized": "PMC12422815" }, "pmid": { "normalized": "40936961" } }, "mesh": [], "publication": { "conference_name": null, "date": "2025 Aug 28", "date_precision": "day", "issue": "4", "normalized_date": "2025-08-28", "pages": "143-152", "proceedings_title": null, "publisher": "", "title": "Acta histochemica et cytochemica", "volume": "58", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Discoidin Domain Receptor 2 (DDR2) Promotes Prostate Cancer Progression in Cooperation with Collagen Remodeling.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Despite the advances in precision oncology through biomarker testing, not all patients are able to benefit from treatment decisions guided by tissue-based testing like comprehensive genomic profiling (CGP). However, the application and integration of liquid biopsy testing into clinical practice has not been fully defined in Japan. Clinical records were retrieved from the data repository of the Center for Cancer Genomics and Advanced Therapeutics (C-CAT) in Japan. All records related to FoundationOne Liquid tests were evaluated from the database's inception in June 2019 to June 2023. Outcomes of interest included treatment patterns before and after testing, as well as mutations of interest. The seven most frequent tumor types (pancreas, prostate, biliary tract, bowel, lung, stomach and ovary) were stratified as part of subgroup analyses. Of 7461 patient records, the most prevalent cancers were pancreatic (24.5%), prostate (15.8%), and biliary tract (11.2%) cancers. Following molecular tumor board (MTB) review, 5.8% of cases received new treatments, predominantly targeted therapy (41.7%) and chemotherapy (40.9%), with 2.1% participating in clinical trials. Median durations from specimen collection to post-MTB treatment were 63 days. Tests for patients with bowel cancer (70/796; 8.8%) and lung cancer (57/695; 8.2%) received genotype-matched treatment most frequently, followed by tests for patients with prostate cancer (92/1182; 7.8%). Access to CGP in Japan appears more limited compared to other high-income countries. While CGP may be valuable for certain cancers, such as bowel, biliary, and prostate cancer, its benefit for other cancer types remains unclear.", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null }, { "creator_type": "author", "first_name": "Ryosuke", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Yuko", "last_name": "Kotera", "name": null }, { "creator_type": "author", "first_name": "Shotaro", "last_name": "Yasuoka", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Ennishi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/cas.70174" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "40859679" } }, "mesh": [ { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Biomarkers, Tumor", "descriptor_ui": "D014408", "major_topic": true }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Japan", "descriptor_ui": "D007564", "major_topic": false }, { "descriptor": "Liquid Biopsy", "descriptor_ui": "D000073890", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Neoplasms", "descriptor_ui": "D009369", "major_topic": true }, { "descriptor": "Precision Medicine", "descriptor_ui": "D057285", "major_topic": false } ], "publication": { "conference_name": null, "date": "2025 Aug 26", "date_precision": "day", "issue": "", "normalized_date": "2025-08-26", "pages": "", "proceedings_title": null, "publisher": "", "title": "Cancer science", "volume": "", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Nationwide Real-World Usage of Blood-Based (Liquid) Biomarker Testing in Japan.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "INTRODUCTION: Metabolites are associated with the biology of cancer; however, no metabolites related to prognosis have been identified in head and neck cancer. This study aimed to identify metabolites associated with prognosis in patients with hypopharyngeal squamous cell carcinoma (HPSCC). METHODS: Fifty-two patients who underwent surgery for HPSCC were included and randomly divided into test and validation cohorts of 26 patients each for further metabolome analysis using capillary electrophoresis/mass spectrometry on tumor and non-tumor tissues of the hypopharynx. Twenty-two patients who received adjuvant therapy after surgery were included. The receiver operating characteristic (ROC) and univariate and multivariate analyses were used to explore the relationship between recurrence-free survival (RFS), clinicopathological factors, and differentiated metabolites. RESULTS: ROC analysis revealed six metabolites significantly associated with RFS in both cohorts, and multivariate analysis indicated that 2,3-pyridinedicarboxylate was a significantly independent poorer prognostic factor in the cohorts including patients with HPSCC without any adjuvant therapies (p = 0.017). CONCLUSION: 2,3-Pyridinedicarboxylate, involved in NAD+ metabolism and genomic stability, suggests the possibility of developing molecular-targeted drugs for the production of metabolites related to prognosis. This study identifies novel prognostic metabolites and their associated metabolic pathways in HPSCC, highlighting potential therapeutic targets for treatment.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Hiroki", "last_name": "Takase", "name": null }, { "creator_type": "author", "first_name": "Takao", "last_name": "Fujisawa", "name": null }, { "creator_type": "author", "first_name": "Ryuichi", "last_name": "Hayashi", "name": null }, { "creator_type": "author", "first_name": "Hideki", "last_name": "Makinoshima", "name": null }, { "creator_type": "author", "first_name": "Yutaka", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Fujii", "name": null } ], "identifiers": { "doi": { "normalized": "10.1159/000548128" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "40875696" } }, "mesh": [ { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Biomarkers, Tumor", "descriptor_ui": "D014408", "major_topic": true }, { "descriptor": "Carcinoma, Squamous Cell", "descriptor_ui": "D002294", "major_topic": true }, { "descriptor": "Disease-Free Survival", "descriptor_ui": "D018572", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Hypopharyngeal Neoplasms", "descriptor_ui": "D007012", "major_topic": true }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Metabolome", "descriptor_ui": "D055442", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Neoplasm Recurrence, Local", "descriptor_ui": "D009364", "major_topic": false }, { "descriptor": "Prognosis", "descriptor_ui": "D011379", "major_topic": false }, { "descriptor": "ROC Curve", "descriptor_ui": "D012372", "major_topic": false }, { "descriptor": "Squamous Cell Carcinoma of Head and Neck", "descriptor_ui": "D000077195", "major_topic": true } ], "publication": { "conference_name": null, "date": "2025 Aug 26", "date_precision": "day", "issue": "", "normalized_date": "2025-08-26", "pages": "1-15", "proceedings_title": null, "publisher": "", "title": "Pathobiology : journal of immunopathology, molecular and cellular biology", "volume": "", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "2,3-Pyridinedicarboxylate Is Associated with Shorter Recurrence-Free Survival in Patients with Hypopharyngeal Squamous Cell Carcinoma.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "INTRODUCTION: Integrated recurrence prediction models that combine clinical, imaging, and genetic data are lacking for epidermal growth factor receptor (EGFR)-mutated stage I non-small cell lung cancer (NSCLC). We developed a recurrence prediction model for Stage I EGFR-mutated NSCLC by integrating clinical, radiological, and whole-exome sequencing (WES) data. METHODS: A total of 306 patients with Stage I EGFR-mutated NSCLC were stratified into training (n = 206) and validation (n = 100) cohorts using stratified random sampling. Cox proportional hazards models combined binary labels of clinical and radiological factors from univariate analysis, machine-learning-derived MultiGenes labels (determined by multiple gene mutations) from WES data, and high-impact gene mutations. Predictive performance was assessed using the concordance index (C-index), time-dependent area under the curve (AUC), and receiver operating characteristic curves. The top three models by category were evaluated using a survival analysis. RESULTS: Three optimal models were identified; the clinicoradiological model (Model 17) achieved a C-index of 0.70, the model incorporating clinicoradiological factors and MultiGenes (Model 28) achieved 0.69, and the clinicoradiological model with TP53 mutations (Model 39) demonstrated the best performance, with 0.73. In Model 17, the 60-month recurrence-free survival (RFS) rates were 59.1 % for the high-risk group and 83.2 % for the low-risk group (hazard ratio [HR] = 3.47; 95 % confidence interval [CI]: 1.60-8.00). Model 39, which incorporated TP53 mutations, demonstrated superior performance, with 60-month RFS rates of 57.1 % for the high-risk and 87.1 % for the low-risk groups (HR = 4.79; 95 %CI: 1.96-11.69). CONCLUSIONS: Clinical and radiological factors are effective predictors of recurrence risk in Stage I EGFR-mutated NSCLC, and incorporating TP53 mutation data further improves the prognostic accuracy.", "classifications": [ { "id": "Hamamoto", "label": "Group Hamamoto", "parent": "Okamoto", "type": "group" }, { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Akiko", "last_name": "Tateishi", "name": null }, { "creator_type": "author", "first_name": "Hidehito", "last_name": "Horinouchi", "name": null }, { "creator_type": "author", "first_name": "Nobuji", "last_name": "Kouno", "name": null }, { "creator_type": "author", "first_name": "Katsuji", "last_name": "Takeda", "name": null }, { "creator_type": "author", "first_name": "Ken", "last_name": "Takasawa", "name": null }, { "creator_type": "author", "first_name": "Takaaki", "last_name": "Mizuno", "name": null }, { "creator_type": "author", "first_name": "Yu", "last_name": "Okubo", "name": null }, { "creator_type": "author", "first_name": "Yukihiro", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Mototaka", "last_name": "Miyake", "name": null }, { "creator_type": "author", "first_name": "Masahiko", "last_name": "Kusumoto", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Inaba", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Igaki", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null }, { "creator_type": "author", "first_name": "Masami", "last_name": "Mukai", "name": null }, { "creator_type": "author", "first_name": "Naoki", "last_name": "Mihara", "name": null }, { "creator_type": "author", "first_name": "Jo", "last_name": "Nishino", "name": null }, { "creator_type": "author", "first_name": "Aya", "last_name": "Kuchiba", "name": null }, { "creator_type": "author", "first_name": "Taro", "last_name": "Shibata", "name": null }, { "creator_type": "author", "first_name": "Kouya", "last_name": "Shiraishi", "name": null }, { "creator_type": "author", "first_name": "Shun-Ichi", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Masaaki", "last_name": "Komatsu", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Kohno", "name": null }, { "creator_type": "author", "first_name": "Yuichiro", "last_name": "Ohe", "name": null }, { "creator_type": "author", "first_name": "Ryuji", "last_name": "Hamamoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.lungcan.2025.108727" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "40876064" } }, "mesh": [ { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Aged, 80 and over", "descriptor_ui": "D000369", "major_topic": false }, { "descriptor": "Carcinoma, Non-Small-Cell Lung", "descriptor_ui": "D002289", "major_topic": true }, { "descriptor": "ErbB Receptors", "descriptor_ui": "D066246", "major_topic": false }, { "descriptor": "Exome Sequencing", "descriptor_ui": "D000073359", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Lung Neoplasms", "descriptor_ui": "D008175", "major_topic": true }, { "descriptor": "Machine Learning", "descriptor_ui": "D000069550", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": true }, { "descriptor": "Neoplasm Recurrence, Local", "descriptor_ui": "D009364", "major_topic": true }, { "descriptor": "Neoplasm Staging", "descriptor_ui": "D009367", "major_topic": false }, { "descriptor": "Prognosis", "descriptor_ui": "D011379", "major_topic": false }, { "descriptor": "ROC Curve", "descriptor_ui": "D012372", "major_topic": false } ], "publication": { "conference_name": null, "date": "2025 Aug 25", "date_precision": "day", "issue": "", "normalized_date": "2025-08-25", "pages": "108727", "proceedings_title": null, "publisher": "", "title": "Lung cancer (Amsterdam, Netherlands)", "volume": "207", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Prediction recurrence in stage I epidermal growth factor receptor-mutated non-small cell lung cancer using multi-modal data.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Thymic epithelial cells (TEC) are crucial in supporting T cell development, but their high heterogeneity and difficulty of isolation pose obstacles to their study in humans. Particularly, how diverse TEC lineages arise from a common progenitor remains poorly understood. To address this, here we establish a human iPSC-based model of thymus organogenesis capable of deriving these lineages in vitro. Through controlled retinoid signaling followed by self-directed differentiation, we obtain FOXN1(+) TEC progenitor-like cells and diverse mature MHCII(+) populations resembling cortical and medullary TECs, allowing us to infer their developmental trajectories. Upon thymocyte co-culture, induced TECs support the generation of naive T cells with diverse TCR repertoires and further develop into AIRE(+) and mimetic TEC subpopulations. Our system provides a fully in vitro model of human TEC differentiation from early fate specification to late-stage maturation, offering new insights into human thymus development and potential regenerative applications for congenital thymic disorders.", "classifications": [ { "id": "Yamamoto", "label": "Group Yamamoto", "parent": "Toyoshima", "type": "group" }, { "id": "Toyoshima", "label": "Team Toyoshima", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yann", "last_name": "Pretemer", "name": null }, { "creator_type": "author", "first_name": "Yuxian", "last_name": "Gao", "name": null }, { "creator_type": "author", "first_name": "Kaho", "last_name": "Kanai", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Kohei", "last_name": "Kometani", "name": null }, { "creator_type": "author", "first_name": "Manami", "last_name": "Ozaki", "name": null }, { "creator_type": "author", "first_name": "Karin", "last_name": "Nishigishi", "name": null }, { "creator_type": "author", "first_name": "Tadashi", "last_name": "Ikeda", "name": null }, { "creator_type": "author", "first_name": "Huaigeng", "last_name": "Xu", "name": null }, { "creator_type": "author", "first_name": "Akitsu", "last_name": "Hotta", "name": null }, { "creator_type": "author", "first_name": "Yoko", "last_name": "Hamazaki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41467-025-62523-1" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "40855082" } }, "mesh": [ { "descriptor": "AIRE Protein", "descriptor_ui": "D000096927", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Cell Lineage", "descriptor_ui": "D019070", "major_topic": true }, { "descriptor": "Coculture Techniques", "descriptor_ui": "D018920", "major_topic": false }, { "descriptor": "Epithelial Cells", "descriptor_ui": "D004847", "major_topic": true }, { "descriptor": "Forkhead Transcription Factors", "descriptor_ui": "D051858", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Induced Pluripotent Stem Cells", "descriptor_ui": "D057026", "major_topic": true }, { "descriptor": "Models, Biological", "descriptor_ui": "D008954", "major_topic": false }, { "descriptor": "Organogenesis", "descriptor_ui": "D038081", "major_topic": false }, { "descriptor": "T-Lymphocytes", "descriptor_ui": "D013601", "major_topic": false }, { "descriptor": "Thymocytes", "descriptor_ui": "D060168", "major_topic": false }, { "descriptor": "Thymus Gland", "descriptor_ui": "D013950", "major_topic": true }, { "descriptor": "Transcription Factors", "descriptor_ui": "D014157", "major_topic": false } ], "publication": { "conference_name": null, "date": "2025 Aug 25", "date_precision": "day", "issue": "1", "normalized_date": "2025-08-25", "pages": "7680", "proceedings_title": null, "publisher": "", "title": "Nature communications", "volume": "16", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "An iPSC-based in vitro model recapitulates human thymic epithelial development and multi-lineage specification.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "", "classifications": [ { "id": "Fujiwara", "label": "Group Fujiwara", "parent": "Fujiwara", "type": "group" }, { "id": "Fujiwara", "label": "Team Fujiwara", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Weiwen", "last_name": "Liu", "name": null }, { "creator_type": "author", "first_name": "Noriko", "last_name": "Sanzen", "name": null }, { "creator_type": "author", "first_name": "Takaya", "last_name": "Abe", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Kiyonari", "name": null }, { "creator_type": "author", "first_name": "Nick", "last_name": "Barker", "name": null }, { "creator_type": "author", "first_name": "Zhiqi", "last_name": "Hu", "name": null }, { "creator_type": "author", "first_name": "Hironobu", "last_name": "Fujiwara", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.jid.2025.07.031" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "40865677" } }, "mesh": [], "publication": { "conference_name": null, "date": "2025 Aug 25", "date_precision": "day", "issue": "", "normalized_date": "2025-08-25", "pages": "S0022-202X(25)02355-3", "proceedings_title": null, "publisher": "", "title": "The Journal of investigative dermatology", "volume": "", "year": 2025 }, "ssbd": { "database": [], "repository": [ "ssbd-repos-000420" ] }, "title": "Nephronectin mediates the interaction between hair follicle epithelial progenitors and dermal stem cells and is involved in hair cycle progression.", "url": "https://www.sciencedirect.com/science/article/pii/S0022202X25023553?via%3Dihub", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Adenocarcinoma in situ (AIS) of the lungs has been increasingly diagnosed worldwide following the establishment of its diagnostic criteria along with advances in computed tomography (CT) imaging technology. We encountered a series of AIS with a peculiar flat cell morphology that were challenging to diagnose using the current diagnostic criteria. Histologically, all five tumors showed a lepidic pattern consisting of flat tumor cells with minimal nuclear atypia. Intra-alveolar mucin was identified in four cases, although cytoplasmic mucin of the tumor cells was inconspicuous. All tumors harbored genetic or immunohistochemical features of neoplasms identical to those of conventional AIS. Driver mutations were detected in three tumors (two EGFR mutations and one ERBB2 mutation), and four tumors were positive for HNF4alpha although the intensity was very low. We also identified a flat cell variant of minimally invasive adenocarcinoma, suggesting a stepwise progression similar to that in conventional AIS. These findings suggest that AIS with flat cellular features is a morphological variant of AIS and may be challenging to diagnose if pathologists are unaware of this atypical feature of lung adenocarcinoma.", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Naoyuki", "last_name": "Oka", "name": null }, { "creator_type": "author", "first_name": "Satsuki", "last_name": "Kishikawa", "name": null }, { "creator_type": "author", "first_name": "Jumpei", "last_name": "Kashima", "name": null }, { "creator_type": "author", "first_name": "Hirokazu", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Masahiko", "last_name": "Kusumoto", "name": null }, { "creator_type": "author", "first_name": "Keisuke", "last_name": "Asakura", "name": null }, { "creator_type": "author", "first_name": "Shun-Ichi", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.modpat.2025.100876" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "40865920" } }, "mesh": [ { "descriptor": "Adenocarcinoma", "descriptor_ui": "D000230", "major_topic": true }, { "descriptor": "Adenocarcinoma in Situ", "descriptor_ui": "D065311", "major_topic": true }, { "descriptor": "Adenocarcinoma of Lung", "descriptor_ui": "D000077192", "major_topic": false }, { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Biomarkers, Tumor", "descriptor_ui": "D014408", "major_topic": false }, { "descriptor": "ErbB Receptors", "descriptor_ui": "D066246", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Immunohistochemistry", "descriptor_ui": "D007150", "major_topic": false }, { "descriptor": "Lung Neoplasms", "descriptor_ui": "D008175", "major_topic": true }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": false } ], "publication": { "conference_name": null, "date": "2025 Aug 25", "date_precision": "day", "issue": "", "normalized_date": "2025-08-25", "pages": "100876", "proceedings_title": null, "publisher": "", "title": "Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc", "volume": "", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Flat Cell Variant of Lung Adenocarcinoma In Situ.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: Lung adenocarcinoma (LUAD) in never-smokers is a major public health burden, especially among East Asian women. Polygenic risk scores (PRSs) are promising for risk stratification but are primarily developed in European-ancestry populations. We aimed to develop and validate single- and multi-ancestry PRSs for East Asian never-smokers to improve LUAD risk prediction. METHODS: PRSs were developed using genome-wide association study summary statistics from East Asian (8,002 cases; 20,782 controls) and European (2,058 cases; 5,575 controls) populations. Single-ancestry models included PRS-25, PRS-CT, and LDpred2; multi-ancestry models included LDpred2+PRS-EUR128, PRS-CSx, and CT-SLEB. Performance was evaluated in independent East Asian data from the Female Lung Cancer Consortium (FLCCA) and externally validated in the Nanjing Lung Cancer Cohort (NJLCC). We assessed predictive accuracy via AUC, with 10-year and (age 30-80) absolute risks estimates. RESULTS: The best multi-ancestry PRS, using East Asian and European data via CT-SLEB (clumping and thresholding, super learning, empirical Bayes), outperformed the best East Asian-only PRS (LDpred2; AUC=0.629, 95% CI:0.618,0.641), achieving an AUC of 0.640 (95% CI:0.629,0.653) and odds ratio of 1.71 (95% CI:1.61,1.82) per SD increase. NJLCC Validation confirmed robust performance (AUC =0.649, 95% CI: 0.623, 0.676). The top 20% PRS group had a 3.92-fold higher LUAD risk than the bottom 20%. Further, the top 5% PRS group reached a 6.69% lifetime absolute risk. Notably, this group reached the average population 10-year LUAD risk at age 50 (0.42%) by age 41, nine years earlier. CONCLUSIONS: Multi-ancestry PRS approaches enhance LUAD risk stratification in East Asian never-smokers, with consistent external validation, suggesting future clinical utility.", "classifications": [ { "id": "Hamamoto", "label": "Group Hamamoto", "parent": "Okamoto", "type": "group" }, { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Batel", "last_name": "Blechter", "name": null }, { "creator_type": "author", "first_name": "Xiaoyu", "last_name": "Wang", "name": null }, { "creator_type": "author", "first_name": "Juncheng", "last_name": "Dai", "name": null }, { "creator_type": "author", "first_name": "Christiana", "last_name": "Karsonaki", "name": null }, { "creator_type": "author", "first_name": "Jianxin", "last_name": "Shi", "name": null }, { "creator_type": "author", "first_name": "Kouya", "last_name": "Shiraishi", "name": null }, { "creator_type": "author", "first_name": "Jiyeon", "last_name": "Choi", "name": null }, { "creator_type": "author", "first_name": "Keitaro", "last_name": "Matsuo", "name": null }, { "creator_type": "author", "first_name": "Tzu-Yu", "last_name": "Chen", "name": null }, { "creator_type": "author", "first_name": "Rayjean J.", "last_name": "Hung", "name": null }, { "creator_type": "author", "first_name": "Kexin", "last_name": "Chen", "name": null }, { "creator_type": "author", "first_name": "Xiao-Ou", "last_name": "Shu", "name": null }, { "creator_type": "author", "first_name": "Young Tae", "last_name": "Kim", "name": null }, { "creator_type": "author", "first_name": "Parichoy Pal", "last_name": "Choudhury", "name": null }, { "creator_type": "author", "first_name": "Jacob", "last_name": "Williams", "name": null }, { "creator_type": "author", "first_name": "Maria Teresa", "last_name": "Landi", "name": null }, { "creator_type": "author", "first_name": "Dongxin", "last_name": "Lin", "name": null }, { "creator_type": "author", "first_name": "Wei", "last_name": "Zheng", "name": null }, { "creator_type": "author", "first_name": "Zhihua", "last_name": "Yin", "name": null }, { "creator_type": "author", "first_name": "Baosen", "last_name": "Zhou", "name": null }, { "creator_type": "author", "first_name": "Jiucun", "last_name": "Wang", "name": null }, { "creator_type": "author", "first_name": "Wei Jie", "last_name": "Seow", "name": null }, { "creator_type": "author", "first_name": "Lei", "last_name": "Song", "name": null }, { "creator_type": "author", "first_name": "I.-Shou", "last_name": "Chang", "name": null }, { "creator_type": "author", "first_name": "Wei", "last_name": "Hu", "name": null }, { "creator_type": "author", "first_name": "Li-Hsin", "last_name": "Chien", "name": null }, { "creator_type": "author", "first_name": "Qiuyin", "last_name": "Cai", "name": null }, { "creator_type": "author", "first_name": "Yun-Chul", "last_name": "Hong", "name": null }, { "creator_type": "author", "first_name": "Hee Nam", "last_name": "Kim", "name": null }, { "creator_type": "author", "first_name": "Yi-Long", "last_name": "Wu", "name": null }, { "creator_type": "author", "first_name": "Maria Pik", "last_name": "Wong", "name": null }, { "creator_type": "author", "first_name": "Brian Douglas", "last_name": "Richardson", "name": null }, { "creator_type": "author", "first_name": "Shilan", "last_name": "Li", "name": null }, { "creator_type": "author", "first_name": "Tongwu", "last_name": "Zhang", "name": null }, { "creator_type": "author", "first_name": "Charles", "last_name": "Breeze", "name": null }, { "creator_type": "author", "first_name": "Zhaoming", "last_name": "Wang", "name": null }, { "creator_type": "author", "first_name": "Bryan A.", "last_name": "Bassig", "name": null }, { "creator_type": "author", "first_name": "Jin Hee", "last_name": "Kim", "name": null }, { "creator_type": "author", "first_name": "Demetrius", "last_name": "Albanes", "name": null }, { 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H.", "last_name": "Vermeulen", "name": null }, { "creator_type": "author", "first_name": "Iona", "last_name": "Cheng", "name": null }, { "creator_type": "author", "first_name": "Junjie", "last_name": "Wu", "name": null }, { "creator_type": "author", "first_name": "Fang-Yu", "last_name": "Tsai", "name": null }, { "creator_type": "author", "first_name": "John K. C.", "last_name": "Chan", "name": null }, { "creator_type": "author", "first_name": "Jihua", "last_name": "Li", "name": null }, { "creator_type": "author", "first_name": "Hsien-Chih", "last_name": "Lin", "name": null }, { "creator_type": "author", "first_name": "Jie", "last_name": "Liu", "name": null }, { "creator_type": "author", "first_name": "Bao", "last_name": "Song", "name": null }, { "creator_type": "author", "first_name": "Norie", "last_name": "Sawada", "name": null }, { "creator_type": "author", "first_name": "Taiki", "last_name": "Yamaji", "name": null }, { "creator_type": "author", "first_name": "Kathleen", "last_name": "Wyatt", "name": null }, { "creator_type": "author", "first_name": "Hongxia", "last_name": "Ma", "name": null }, { "creator_type": "author", "first_name": "Meng", "last_name": "Zhu", "name": null }, { "creator_type": "author", "first_name": "Yifan", "last_name": "Wang", "name": null }, { "creator_type": "author", "first_name": "Tianchen", "last_name": "Qi", "name": null }, { "creator_type": "author", "first_name": "Xuelian", "last_name": "Li", "name": null }, { "creator_type": "author", "first_name": "Yangwu", "last_name": "Ren", "name": null }, { "creator_type": "author", "first_name": "Ann", "last_name": "Chao", "name": null }, { "creator_type": "author", "first_name": "Motoki", "last_name": "Iwasaki", "name": null }, { "creator_type": "author", "first_name": "Junjie", "last_name": "Zhu", "name": null }, { "creator_type": "author", "first_name": "Guoping", "last_name": "Wu", "name": null }, { "creator_type": "author", "first_name": "Chih-Yi", "last_name": "Chen", "name": null }, { "creator_type": "author", "first_name": "Chien-Jen", "last_name": "Chen", "name": null }, { "creator_type": "author", "first_name": "Pan-Chyr", "last_name": "Yang", "name": null }, { "creator_type": "author", "first_name": "Victoria L.", "last_name": "Stevens", "name": null }, { "creator_type": "author", "first_name": "Joseph F. Jr", "last_name": "Fraumeni", "name": null }, { "creator_type": "author", "first_name": "Kuang", "last_name": "Lin", "name": null }, { "creator_type": "author", "first_name": "Robin G.", "last_name": "Walters", "name": null }, { "creator_type": "author", "first_name": "Zhengming", "last_name": "Chen", "name": null }, { "creator_type": "author", "first_name": "Nilanjan", "last_name": "Chatterjee", "name": null }, { "creator_type": "author", "first_name": "Olga Y.", "last_name": "Gorlova", "name": null }, { "creator_type": "author", "first_name": "Christopher I.", "last_name": "Amos", "name": null }, { "creator_type": "author", "first_name": "Hongbing", "last_name": "Shen", "name": null }, { "creator_type": "author", "first_name": "Chao Agnes", "last_name": "Hsiung", "name": null }, { "creator_type": "author", "first_name": "Stephen J.", "last_name": "Chanock", "name": null }, { "creator_type": "author", "first_name": "Nathaniel", "last_name": "Rothman", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Kohno", "name": null }, { "creator_type": "author", "first_name": "Qing", "last_name": "Lan", "name": null }, { "creator_type": "author", "first_name": "Haoyu", "last_name": "Zhang", "name": null } ], "identifiers": { "doi": { "normalized": "10.1101/2024.06.26.24309127" }, "pmcid": { "normalized": null }, "pmid": { "normalized": null } }, "mesh": [], "publication": { "conference_name": null, "date": "2025 Aug 24", "date_precision": "day", "issue": null, "normalized_date": "2025-08-24", "pages": null, "proceedings_title": null, "publisher": null, "title": null, "volume": null, "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Stratifying Lung Adenocarcinoma Risk with Multi-ancestry Polygenic Risk Scores in East Asian Never-Smokers.", "url": "", "zotero": { "item_type": "preprint" } }, { "abstract": "Fluorescence microscopy enables the visualization of cellular morphology, molecular distribution, ion distribution, and their dynamic behaviors during biological processes. Enhancing the signal-to-noise ratio (SNR) in fluorescence imaging improves the quantification accuracy and spatial resolution; however, achieving high SNR at fast image acquisition rates, which is often required to observe cellular dynamics, still remains a challenge. In this study, we developed a technique to rapidly freeze biological cells in milliseconds during optical microscopy observation. Compared to chemical fixation, rapid freezing provides rapid immobilization of samples while more effectively preserving the morphology and conditions of cells. This technique combines the advantages of both live-cell and cryofixation microscopy, i.e., temporal dynamics and high SNR snapshots of selected moments, and is demonstrated by fluorescence and Raman microscopy with high spatial resolution and quantification under low temperature conditions. Furthermore, we also demonstrated that intracellular calcium dynamics can be frozen rapidly and visualized using fluorescent ion indicators, suggesting that ion distribution and conformation of the probe molecules can be fixed both spatially and temporally. These results confirmed that our technique can time-deterministically suspend and visualize cellular dynamics while preserving molecular and ionic states, indicating the potential to provide detailed insights into sample dynamics with improved spatial resolution and temporal accuracy in observations.", "classifications": [ { "id": "JPMJCR1925", "label": "JPMJCR1925", "researcher": "Katsumasa Fujita", "type": "grant" }, { "id": "Fujita", "label": "Group Fujita", "parent": "Fujita", "type": "group" }, { "id": "Tanaka", "label": "Group Tanaka", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Kosuke", "last_name": "Tsuji", "name": null }, { "creator_type": "author", "first_name": "Masahito", "last_name": "Yamanaka", "name": null }, { "creator_type": "author", "first_name": "Yasuaki", "last_name": "Kumamoto", "name": null }, { "creator_type": "author", "first_name": "Shoko", "last_name": "Tamura", "name": null }, { "creator_type": "author", "first_name": "Wakana", "last_name": "Miyamura", "name": null }, { "creator_type": "author", "first_name": "Toshiki", "last_name": "Kubo", "name": null }, { "creator_type": "author", "first_name": "Kenta", "last_name": "Mizushima", "name": null }, { "creator_type": "author", "first_name": "Kakeru", "last_name": "Kono", "name": null }, { "creator_type": "author", "first_name": "Hanae", "last_name": "Hirano", "name": null }, { "creator_type": "author", "first_name": "Momoko", "last_name": "Shiozaki", "name": null }, { "creator_type": "author", "first_name": "Xiaowei", "last_name": "Zhao", "name": null }, { "creator_type": "author", "first_name": "Heqi", "last_name": "Xi", "name": null }, { "creator_type": "author", "first_name": "Kazunori", "last_name": "Sugiura", "name": null }, { "creator_type": "author", "first_name": "Shun-Ichi", "last_name": "Fukushima", "name": null }, { "creator_type": "author", "first_name": "Takumi", "last_name": "Kunimoto", "name": null }, { "creator_type": "author", "first_name": "Yoshino", "last_name": "Tanabe", "name": null }, { "creator_type": "author", "first_name": "Kentaro", "last_name": "Nishida", "name": null }, { "creator_type": "author", "first_name": "Kentaro", "last_name": "Mochizuki", "name": null }, { "creator_type": "author", "first_name": "Yoshinori", "last_name": "Harada", "name": null }, { "creator_type": "author", "first_name": "Nicholas I.", "last_name": "Smith", "name": null }, { "creator_type": "author", "first_name": "Rainer", "last_name": "Heintzmann", "name": null }, { "creator_type": "author", "first_name": "Zhiheng", "last_name": "Yu", "name": null }, { "creator_type": "author", "first_name": "Meng C.", "last_name": "Wang", "name": null }, { "creator_type": "author", "first_name": "Takeharu", "last_name": "Nagai", "name": null }, { "creator_type": "author", "first_name": "Hideo", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Katsumasa", "last_name": "Fujita", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41377-025-01941-8" }, "pmcid": { "normalized": "PMC12373960" }, "pmid": { "normalized": "40846863" } }, "mesh": [], "publication": { "conference_name": null, "date": "2025 Aug 23", "date_precision": "day", "issue": "1", "normalized_date": "2025-08-23", "pages": "275", "proceedings_title": null, "publisher": "", "title": "Light, science & applications", "volume": "14", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Time-deterministic cryo-optical microscopy.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Fusion genes between the FET (EWSR1/FUS) and CREB (CREB1, ATF1, CREM) families characterize many tumor types, including mesenchymal entities. Herein, we tested the diagnostic utility of CREM (C-terminus) immunohistochemistry using 51 CREB-rearranged mesenchymal tumors and 159 tumors of 14 mimicking entities. Staining was considered positive if nuclear staining of moderate or strong intensity was observed in at least 10% of the tumor cells. Among the 51 CREB-rearranged tumors, CREM was at least focally positive in 39 tumors (76.5%), diffusely (>/= 50%) positive in 31 tumors (60.8%), and diffuse strong staining was observed in 23 tumors (45.1%). Diffuse strong reactivity was observed in nearly all angiomatoid fibrous histiocytoma (11 of 12 tumors), intracranial FET::CREB mesenchymal neoplasms (2 of 2 tumors), and unclassifiable sarcomas (2 of 2 tumors, including 1 case with SMARCA2::CREM). However, the positivity was more limited in clear cell sarcoma (15 of 20 tumors), keratin-positive malignant FET::CREB tumors in the abdomen (5 of 8 tumors), and gastrointestinal neuroectodermal tumors (4 of 7 tumors). Two separately evaluated CRTC1-rearranged tumors (CRTC1::TRIM11 and CRTC1::SS18) demonstrated diffuse strong positivity. Among the 159 tumors in the comparison cohort, CREM was at least focally positive in 33 (20.8%) tumors, diffusely positive in 19 tumors (11.9%), and diffusely and strongly positive in 5 tumors (3.1%). CREM demonstrated moderate sensitivity and specificity for the diagnosis of CREB-rearranged mesenchymal tumors as a whole cohort, and its overall utility in predicting CREB fusion is limited. However, CREM staining may be useful in a few specific contexts, such as when angiomatoid fibrous histiocytoma is suspected.", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Shogo", "last_name": "Nishino", "name": null }, { "creator_type": "author", "first_name": "Hirokazu", "last_name": "Sugino", "name": null }, { "creator_type": "author", "first_name": "Yasuhito", "last_name": "Arai", "name": null }, { "creator_type": "author", "first_name": "Natsuko", "last_name": "Hama", "name": null }, { "creator_type": "author", "first_name": "Tatsuhiro", "last_name": "Shibata", "name": null }, { "creator_type": "author", "first_name": "Shuhei", "last_name": "Osaki", "name": null }, { "creator_type": "author", "first_name": "Seiichi", "last_name": "Yoshimoto", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null }, { "creator_type": "author", "first_name": "Taisuke", "last_name": "Mori", "name": null }, { "creator_type": "author", "first_name": "Akihiko", "last_name": "Yoshida", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/s00428-025-04207-1" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "40849561" } }, "mesh": [ { "descriptor": "Adolescent", "descriptor_ui": "D000293", "major_topic": false }, { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Biomarkers, Tumor", "descriptor_ui": "D014408", "major_topic": true }, { "descriptor": "Child", "descriptor_ui": "D002648", "major_topic": false }, { "descriptor": "Child, Preschool", "descriptor_ui": "D002675", "major_topic": false }, { "descriptor": "Cyclic AMP Response Element Modulator", "descriptor_ui": "D051786", "major_topic": true }, { "descriptor": "Cyclic AMP Response Element-Binding Protein", "descriptor_ui": "D017362", "major_topic": true }, { "descriptor": "Diagnosis, Differential", "descriptor_ui": "D003937", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Gene Rearrangement", "descriptor_ui": "D015321", "major_topic": false }, { "descriptor": "Histiocytoma, Malignant Fibrous", "descriptor_ui": "D051677", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Immunohistochemistry", "descriptor_ui": "D007150", "major_topic": true }, { "descriptor": "Infant", "descriptor_ui": "D007223", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Sarcoma", "descriptor_ui": "D012509", "major_topic": true }, { "descriptor": "Young Adult", "descriptor_ui": "D055815", "major_topic": false } ], "publication": { "conference_name": null, "date": "2025 Aug 23", "date_precision": "day", "issue": "", "normalized_date": "2025-08-23", "pages": "", "proceedings_title": null, "publisher": "", "title": "Virchows Archiv : an international journal of pathology", "volume": "", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Immunohistochemical evaluation of CREM in CREB-rearranged mesenchymal tumors and their mimics.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The gut undergoes peristaltic movements regulated by intricate cellular interactions. How these interactions emerge in the developing gut remains poorly explored due to a lack of model system. We here developed a novel contractile organoid that is derived from the muscle layer of chicken embryonic hindgut. The organoid contained smooth muscle cells (SMCs) and interstitial cells of Cajal (ICCs; pacemaker) with few enteric neurons and underwent periodic contractions. The organoid was formed by self-organization with morphological arrangements of ICCs (internal) and SMCs (peripheral), allowing identification of these cells in live. GCaMP-Ca(2+) imaging analyses revealed that Ca(2+) transients between ICC-ICC, SMC-SMC, or SMC-ICC were markedly coordinated. Pharmacological studies further suggested a role of gap junctions in ICC-to-SMC signaling, and also possible mechanical feedback from SMC's contraction to ICC's pace-making activities. In addition, two organoids with different rhythms became synchronized when mediated by SMCs, unveiling a novel contribution of SMCs to ICC's pace-making. The gut contractile organoid developed in this study offers a useful model to understand how the rhythm coordination between/among ICCs and SMCs is regulated and maintained during gut development.", "classifications": [ { "id": "Eiraku", "label": "Group Eiraku", "parent": "Eiraku", "type": "group" }, { "id": "Eiraku", "label": "Team Eiraku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Rei", "last_name": "Yagasaki", "name": null }, { "creator_type": "author", "first_name": "Ryo", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Yuuki", "last_name": "Shikaya", "name": null }, { "creator_type": "author", "first_name": "Ryosuke", "last_name": "Tadokoro", "name": null }, { "creator_type": "author", "first_name": "Ruolin", "last_name": "Hao", "name": null }, { "creator_type": "author", "first_name": "Zhe", "last_name": "Wang", "name": null }, { "creator_type": "author", "first_name": "Mototsugu", "last_name": "Eiraku", "name": null }, { "creator_type": "author", "first_name": "Masafumi", "last_name": "Inaba", "name": null }, { "creator_type": "author", "first_name": "Yoshiko", "last_name": "Takahashi", "name": null } ], "identifiers": { "doi": { "normalized": "10.7554/elife.97860" }, "pmcid": { "normalized": "PMC12373395" }, "pmid": { "normalized": "40843588" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Calcium", "descriptor_ui": "D002118", "major_topic": false }, { "descriptor": "Cell Communication", "descriptor_ui": "D002450", "major_topic": false }, { "descriptor": "Chick Embryo", "descriptor_ui": "D002642", "major_topic": false }, { "descriptor": "Chickens", "descriptor_ui": "D002645", "major_topic": false }, { "descriptor": "Gastrointestinal Motility", "descriptor_ui": "D005769", "major_topic": true }, { "descriptor": "Interstitial Cells of Cajal", "descriptor_ui": "D056885", "major_topic": true }, { "descriptor": "Muscle Contraction", "descriptor_ui": "D009119", "major_topic": true }, { "descriptor": "Muscle, Smooth", "descriptor_ui": "D009130", "major_topic": true }, { "descriptor": "Myocytes, Smooth Muscle", "descriptor_ui": "D032389", "major_topic": true }, { "descriptor": "Organoids", "descriptor_ui": "D009940", "major_topic": true }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false } ], "publication": { "conference_name": null, "date": "2025 Aug 22", "date_precision": "day", "issue": "", "normalized_date": "2025-08-22", "pages": "", "proceedings_title": null, "publisher": "", "title": "eLife", "volume": "13", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "The gut contractile organoid for studying the gut motility regulated by coordinating signals between interstitial cells of Cajal and smooth muscles.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "OBJECTIVE: Increased de novo fatty acid (FA) synthesis is a hallmark of cancer. ELOVL FA elongase 6 (ELOVL6) catalyze chain elongation of C16 saturated and monounsaturated FAs into C18 species and has been implicated in several cancers. This study investigated the role of ELOVL6 in bladder cancer (BC). METHODS: ELOVL6 expression was compared between BC and nontumor tissues. Human BC cell lines with ELOVL6-knockdown were assessed for proliferation and tumor growth. Metabolic and molecular alterations induced by ELOVL6 inhibition were analyzed using lipidomics and transcriptomics. RESULTS: ELOVL6 expression was significantly higher in BC tissues than in controls. In fibroblast growth factor receptor 3 (FGFR3)-mutant BC cell lines, ELOVL6 knockdown suppressed cell growth in vitro and tumor progression in vivo. Lipidomic analysis showed a marked reduction in phosphatidylethanolamine following ELOVL6 knockdown, which was accompanied by lower mitochondrial complex I and II protein levels and impaired mitochondrial oxidative phosphorylation (OXPHOS). RNA sequencing revealed that mitochondrial dysfunction resulting from ELOVL6 knockdown triggered changes in extracellular matrix (ECM) remodeling gene expression and activation of the ECM-integrin-focal adhesion kinase (FAK) pathway, likely as a compensatory response to reduced cell proliferation. CONCLUSION: ELOVL6 regulates lipid composition to preserve mitochondrial function, supporting cell growth and tumorigenesis in FGFR3-mutated BC. Targeting ELOVL6 may represent a novel therapeutic strategy for treating BC, particularly in tumors driven by FGFR3 mutations.", "classifications": [ { "id": "Miyamoto", "label": "Group Miyamoto", "parent": "Wakamoto", "type": "group" }, { "id": "Wakamoto", "label": "Team Wakamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Erika", "last_name": "Matsuda", "name": null }, { "creator_type": "author", "first_name": "Shiho", "last_name": "Hasebe", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Matsuzaka", "name": null }, { "creator_type": "author", "first_name": "Akio", "last_name": "Hayashi", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Ohno", "name": null }, { "creator_type": "author", "first_name": "Kaori", "last_name": "Motomura", "name": null }, { "creator_type": "author", "first_name": "Shotaro", "last_name": "Sakka", "name": null }, { "creator_type": "author", "first_name": "Susumu", "last_name": "Kohno", "name": null }, { "creator_type": "author", "first_name": "Hayato", "last_name": "Muranaka", "name": null }, { "creator_type": "author", "first_name": "Minako", "last_name": "Yamamura", "name": null }, { "creator_type": "author", "first_name": "Asuka", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Yoshinori", "last_name": "Takeuchi", "name": null }, { "creator_type": "author", "first_name": "Yoshinori", "last_name": "Osaki", "name": null }, { "creator_type": "author", "first_name": "Takafumi", "last_name": "Miyamoto", "name": null }, { "creator_type": "author", "first_name": "Motohiro", "last_name": "Sekiya", "name": null }, { "creator_type": "author", "first_name": "Hirohito", "last_name": "Sone", "name": null }, { "creator_type": "author", "first_name": "Naoya", "last_name": "Yahagi", "name": null }, { "creator_type": "author", "first_name": "Yoshimi", "last_name": "Nakagawa", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Nitta", "name": null }, { "creator_type": "author", "first_name": "Shuya", "last_name": "Kandori", "name": null }, { "creator_type": "author", "first_name": "Takahiro", "last_name": "Kojima", "name": null }, { "creator_type": "author", "first_name": "Chiaki", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Nishiyama", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Shimano", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.bbadis.2025.168023" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "40835210" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Cell Proliferation", "descriptor_ui": "D049109", "major_topic": false }, { "descriptor": "Disease Progression", "descriptor_ui": "D018450", "major_topic": false }, { "descriptor": "Fatty Acid Elongases", "descriptor_ui": "D000081031", "major_topic": true }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Gene Expression Regulation, Neoplastic", "descriptor_ui": "D015972", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mitochondria", "descriptor_ui": "D008928", "major_topic": true }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": true }, { "descriptor": "Oxidative Phosphorylation", "descriptor_ui": "D010085", "major_topic": false }, { "descriptor": "Receptor, Fibroblast Growth Factor, Type 3", "descriptor_ui": "D051498", "major_topic": true }, { "descriptor": "Urinary Bladder Neoplasms", "descriptor_ui": "D001749", "major_topic": true } ], "publication": { "conference_name": null, "date": "2025 Aug 18", "date_precision": "day", "issue": "8", "normalized_date": "2025-08-18", "pages": "168023", "proceedings_title": null, "publisher": "", "title": "Biochimica et biophysica acta. Molecular basis of disease", "volume": "1871", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Inhibition of ELOVL6 activity impairs mitochondrial respiratory function and inhibits tumor progression in FGFR3-mutated bladder cancer cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The T cell receptor (TCR) repertoire is a valuable source of information that reflects an individual's immune status and infection history. However, due to the exceptional diversity and complexity of the TCR repertoire, predicting its functional properties remains a challenging task. This review summarizes recent advances in protein language models (PLMs), which apply natural language processing techniques to protein sequences, focusing specifically on TCR repertoire analysis. We begin by outlining the biological basis of the TCR repertoire and its current clinical applications. We then describe the methods used for representing TCR data and the training procedures of the corresponding PLMs. PLMs capture context-dependent features from large unlabeled TCR datasets and achieve high generalization performance even with limited labeled data through transfer learning. In this respect, PLMs offer significant advantages over conventional sequence representation methods. We highlight antigen specificity prediction as a key application, comparing supervised deep learning models with PLM-based approaches. While employment of PLMs is promising, TCR repertoire analysis still faces challenges such as data scarcity, bias, and lack of paired-chain information. Addressing these challenges requires rigorous dataset optimization, integration, and augmentation strategies. Future advances will require better interpretation of the representations learned by PLMs and the development of multimodal approaches that integrate structural information. These advances could enable several clinical applications, including disease diagnosis, vaccine development, and personalized immune profiling.", "classifications": [ { "id": "Kobayashi", "label": "Group Kobayashi", "parent": "Wakamoto", "type": "group" }, { "id": "Wakamoto", "label": "Team Wakamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Kyohei", "last_name": "Kinoshita", "name": null }, { "creator_type": "author", "first_name": "Tetsuya J.", "last_name": "Kobayashi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1093/intimm/dxaf048" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "40855636" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Deep Learning", "descriptor_ui": "D000077321", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Natural Language Processing", "descriptor_ui": "D009323", "major_topic": true }, { "descriptor": "Receptors, Antigen, T-Cell", "descriptor_ui": "D011948", "major_topic": true } ], "publication": { "conference_name": null, "date": "2025 Aug 16", "date_precision": "day", "issue": "", "normalized_date": "2025-08-16", "pages": "dxaf048", "proceedings_title": null, "publisher": "", "title": "International immunology", "volume": "", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "TCR representation learning with protein language models: a comprehensive review.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The specification of primordial germ cells (PGCs) marks a crucial branchpoint in early embryonic development. Studying the molecular mechanisms governing this process is crucial for understanding reproduction and evolution. Here, we identify transcription factors essential for PGC specification in rats using an in vitro system to induce PGC-like cells (PGCLCs) from pluripotent cells. Overexpression of Tbxt, a key mesodermal factor activating the germ cell program in epiblast-like cells, induces functional rat PGCLCs, similar to mice. However, unlike in mice, overexpression of the PGC specifiers (Prdm14, Blimp1, and Ap2gamma) alone is not sufficient in rats; additional Activin and WNT signals are necessary for PGCLC induction. Through a candidate screen, we identified the transcription factor Etv4 acting cooperatively with the three PGC specifiers. Our study provides insight into the mechanism behind germline segregation in mammals and underscores the importance of using the rat model in addition to mice.", "classifications": [ { "id": "Yamamoto", "label": "Group Yamamoto", "parent": "Toyoshima", "type": "group" }, { "id": "Toyoshima", "label": "Team Toyoshima", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Mami", "last_name": "Oikawa", "name": null }, { "creator_type": "author", "first_name": "Hiroki", "last_name": "Kojima", "name": null }, { "creator_type": "author", "first_name": "Hisato", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Kenyu", "last_name": "Iwatsuki", "name": null }, { "creator_type": "author", "first_name": "Hijiri", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Sanbo", "name": null }, { "creator_type": "author", "first_name": "Kazumi", "last_name": "Nishioka", "name": null }, { "creator_type": "author", "first_name": "Tomoyuki", "last_name": "Yamaguchi", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Kazuki", "last_name": "Kurimoto", "name": null }, { "creator_type": "author", "first_name": "Masumi", "last_name": "Hirabayashi", "name": null }, { "creator_type": "author", "first_name": "Toshihiro", "last_name": "Kobayashi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.stemcr.2025.102599" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "40803291" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Gene Expression Regulation, Developmental", "descriptor_ui": "D018507", "major_topic": false }, { "descriptor": "Germ Cells", "descriptor_ui": "D005854", "major_topic": true }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Positive Regulatory Domain I-Binding Factor 1", "descriptor_ui": "D000074462", "major_topic": false }, { "descriptor": "Proto-Oncogene Proteins c-ets", "descriptor_ui": "D050783", "major_topic": true }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Transcription Factors", "descriptor_ui": "D014157", "major_topic": true } ], "publication": { "conference_name": null, "date": "2025 Aug 12", "date_precision": "day", "issue": "8", "normalized_date": "2025-08-12", "pages": "102599", "proceedings_title": null, "publisher": "", "title": "Stem cell reports", "volume": "20", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Transcription factor-mediated germ cell induction in rats reveals ETV4 cooperates with germline specifiers.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Human papillomavirus (HPV) infection contributes to the development of almost all cervical malignancies, aside from gastric-type adenocarcinoma of the cervix (GAS), a rare aggressive subtype without HPV infection. To address the carcinogenic mechanism of this disease, we performed a comparative multi-omics analysis of GAS and usual-type endocervical adenocarcinoma (UEA) in three independent cohorts of patients with GAS and UEA. The first cohort comprised eight GAS and 22 UEA patients treated at the National Cancer Center Hospital between 2002 and 2020, who were examined by targeted and whole transcriptome sequencing. The other two cohorts comprised 52 GAS and 109 UEA patients and 39 GAS and 232 UEA patients, whose mutational data were obtained from the C-CAT (Japanese patients) and GENIE (US patients) public databases, respectively. Metabolomic analysis was performed in eight patients, including five with GAS. TP53 mutations were more prevalent in GAS than in UEA in all three cohorts. Transcriptome analysis consistently revealed frequent suppression of TP53-related pathways in GAS. Metabolites preferentially detected in GAS tissues suggest TP53 alterations are implicated in intratumoral metabolic properties. The development of GAS is likely driven by TP53 mutations, which play a large role in shaping intracellular signaling and metabolic profiles within tumor cells.", "classifications": [ { "id": "Hamamoto", "label": "Group Hamamoto", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Daiki", "last_name": "Higuchi", "name": null }, { "creator_type": "author", "first_name": "Maiko", "last_name": "Yamaguchi", "name": null }, { "creator_type": "author", "first_name": "Erisa", "last_name": "Fujii", "name": null }, { "creator_type": "author", "first_name": "Mayumi Kobayashi", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Kengo", "last_name": "Hiranuma", "name": null }, { "creator_type": "author", "first_name": "Yuka", "last_name": "Asami", "name": null }, { "creator_type": "author", "first_name": "Hanako", "last_name": "Ono", "name": null }, { "creator_type": "author", "first_name": "Takafumi", "last_name": "Koyama", "name": null }, { "creator_type": "author", "first_name": "Masaaki", "last_name": "Komatsu", "name": null }, { "creator_type": "author", "first_name": "Ryuji", "last_name": "Hamamoto", "name": null }, { "creator_type": "author", "first_name": "Yasuhisa", "last_name": "Terao", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Matsumoto", "name": null }, { "creator_type": "author", "first_name": "Akihiko", "last_name": "Sekizawa", "name": null }, { "creator_type": "author", "first_name": "Mitsuya", "last_name": "Ishikawa", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Kohno", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Hideki", "last_name": "Makinoshima", "name": null }, { "creator_type": "author", "first_name": "Kouya", "last_name": "Shiraishi", "name": null }, { "creator_type": "author", "first_name": "Tomoyasu", "last_name": "Kato", "name": null } ], "identifiers": { "doi": { "normalized": "10.1093/jncics/pkaf082" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "40796139" } }, "mesh": [ { "descriptor": "Adenocarcinoma", "descriptor_ui": "D000230", "major_topic": true }, { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Cohort Studies", "descriptor_ui": "D015331", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Genes, p53", "descriptor_ui": "D016158", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Metabolomics", "descriptor_ui": "D055432", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": false }, { "descriptor": "Stomach Neoplasms", "descriptor_ui": "D013274", "major_topic": true }, { "descriptor": "Tumor Suppressor Protein p53", "descriptor_ui": "D016159", "major_topic": true }, { "descriptor": "Uterine Cervical Neoplasms", "descriptor_ui": "D002583", "major_topic": true } ], "publication": { "conference_name": null, "date": "2025 Aug 11", "date_precision": "day", "issue": "", "normalized_date": "2025-08-11", "pages": "pkaf082", "proceedings_title": null, "publisher": "", "title": "JNCI cancer spectrum", "volume": "", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "TP53 gene and pathway alterations in gastric-type adenocarcinoma of the cervix.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "", "classifications": [ { "id": "Akaike", "label": "Group Akaike", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Pattanachat", "last_name": "Lertpeerapan", "name": null }, { "creator_type": "author", "first_name": "Songphon", "last_name": "Kanlayaprasit", "name": null }, { "creator_type": "author", "first_name": "Surangrat", "last_name": "Thongkorn", "name": null }, { "creator_type": "author", "first_name": "Kasidit", "last_name": "Kasitipradit", "name": null }, { "creator_type": "author", "first_name": "Pawinee", "last_name": "Panjabud", "name": null }, { "creator_type": "author", "first_name": "Kwanjira", "last_name": "Songsritaya", "name": null }, { "creator_type": "author", "first_name": "Thanawin", "last_name": "Jantheang", "name": null }, { "creator_type": "author", "first_name": "Masanobu", "last_name": "Morita", "name": null }, { "creator_type": "author", "first_name": "Takaaki", "last_name": "Akaike", "name": null }, { "creator_type": "author", "first_name": "Valerie W.", "last_name": "Hu", "name": null }, { "creator_type": "author", "first_name": "Depicha", "last_name": "Jindatip", "name": null }, { "creator_type": "author", "first_name": "Thanit", "last_name": "Saeliw", "name": null }, { "creator_type": "author", "first_name": "Tewarit", "last_name": "Sarachana", "name": null } ], "identifiers": { "doi": { "normalized": "10.1186/s13293-025-00744-1" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "40790242" } }, "mesh": [ { "descriptor": "Alternative Splicing", "descriptor_ui": "D017398", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Benzhydryl Compounds", "descriptor_ui": "D001559", "major_topic": true }, { "descriptor": "Bisphenol A Compounds", "descriptor_ui": "D000098826", "major_topic": false }, { "descriptor": "Down-Regulation", "descriptor_ui": "D015536", "major_topic": false }, { "descriptor": "Endocrine Disruptors", "descriptor_ui": "D052244", "major_topic": true }, { "descriptor": "Epigenesis, Genetic", "descriptor_ui": "D044127", "major_topic": true }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Hippocampus", "descriptor_ui": "D006624", "major_topic": true }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Phenols", "descriptor_ui": "D010636", "major_topic": true }, { "descriptor": "Poly(A)-Binding Proteins", "descriptor_ui": "D039102", "major_topic": true }, { "descriptor": "Pregnancy", "descriptor_ui": "D011247", "major_topic": false }, { "descriptor": "Prenatal Exposure Delayed Effects", "descriptor_ui": "D011297", "major_topic": true }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Rats, Sprague-Dawley", "descriptor_ui": "D017207", "major_topic": false }, { "descriptor": "RNA-Binding Proteins", "descriptor_ui": "D016601", "major_topic": true }, { "descriptor": "Sex Characteristics", "descriptor_ui": "D012727", "major_topic": true }, { "descriptor": "YY1 Transcription Factor", "descriptor_ui": "D050986", "major_topic": true } ], "publication": { "conference_name": null, "date": "2025 Aug 11", "date_precision": "day", "issue": "1", "normalized_date": "2025-08-11", "pages": "63", "proceedings_title": null, "publisher": "", "title": "Biology of sex differences", "volume": "16", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Sex-dependent epigenetic disruption of YY1 binding by prenatal BPA exposure downregulates Matr3 and alters Agap1 splicing in the offspring hippocampus.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "High-resolution live imaging of regeneration presents unique challenges due to the nature of the specimens (large mobile animals), the duration of the process (spanning days or weeks), and the fact that cellular resolution must be achieved without damage caused by lengthy exposures to light. Building on previous work that allowed us to image different parts of the process of leg regeneration in the crustacean Parhyale hawaiensis, we present here a method for live imaging that captures the entire process of leg regeneration, spanning up to 10 days, at cellular resolution. Our method includes (1) mounting and long-term live imaging of regenerating legs under conditions that yield high spatial and temporal resolution but minimise photodamage, (2) fixing and in situ staining of the regenerated legs that were imaged, to identify cell fates, and (3) computer-assisted cell tracking to determine the cell lineages and progenitors of identified cells. The method is optimised to limit light exposure while maximising tracking efficiency. Combined with appropriate cell-type-specific markers, this method may allow the description of cell lineages for every regenerated cell type in the limb.", "classifications": [ { "id": "JPMJCR1926", "label": "JPMJCR1926", "researcher": "Hironobu Fujiwara", "type": "grant" }, { "id": "Fujiwara", "label": "Group Fujiwara", "parent": "Fujiwara", "type": "group" }, { "id": "Fujiwara", "label": "Team Fujiwara", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Cagri", "last_name": "Cevrim", "name": null }, { "creator_type": "author", "first_name": "Beryl", "last_name": "Laplace-Builhe", "name": null }, { "creator_type": "author", "first_name": "Ko", "last_name": "Sugawara", "name": null }, { "creator_type": "author", "first_name": "Maria Lorenza", "last_name": "Rusciano", "name": null }, { "creator_type": "author", "first_name": "Nicolas", "last_name": "Labert", "name": null }, { "creator_type": "author", "first_name": "Jacques", "last_name": "Brocard", "name": null }, { "creator_type": "author", "first_name": "Alba", "last_name": "Almazan", "name": null }, { "creator_type": "author", "first_name": "Michalis", "last_name": "Averof", "name": null } ], "identifiers": { "doi": { "normalized": "10.7554/elife.107534" }, "pmcid": { "normalized": "PMC12334163" }, "pmid": { "normalized": "40778836" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Tracking", "descriptor_ui": "D058948", "major_topic": true }, { "descriptor": "Crustacea", "descriptor_ui": "D003445", "major_topic": true }, { "descriptor": "Extremities", "descriptor_ui": "D005121", "major_topic": true }, { "descriptor": "Regeneration", "descriptor_ui": "D012038", "major_topic": true } ], "publication": { "conference_name": null, "date": "2025 Aug 8", "date_precision": "day", "issue": "", "normalized_date": "2025-08-08", "pages": "", "proceedings_title": null, "publisher": "", "title": "eLife", "volume": "14", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Long-term live imaging, cell identification and cell tracking in regenerating crustacean legs.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Despite growing interest in space exploration, the effects of spaceflight on stem cells remain largely unknown. Damages to germline cells are especially crucial, as spaceflight poses risks to gametogenesis, with abnormalities observed in multiple species. While embryonic stem (ES) cells show genomic instability after space exposure and have not yet produced offspring, this study demonstrates successful offspring production from cryopreserved mouse spermatogonial stem cells (SSCs) stored on the International Space Station for 6 months. Spaceflight did not increase apoptosis or DNA damage in SSCs. After thawing, SSCs proliferated comparably to those cryopreserved on Earth, showing no significant phenotypic or functional differences. Offspring were produced via spermatogonial transplantation followed by natural mating. Since SSCs from many species can be cryopreserved like somatic cells and still produce sperm, they offer a promising resource for germline preservation during space exploration.", "classifications": [ { "id": "Yamamoto", "label": "Group Yamamoto", "parent": "Toyoshima", "type": "group" }, { "id": "Toyoshima", "label": "Team Toyoshima", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Mito", "last_name": "Kanatsu-Shinohara", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Shiromoto", "name": null }, { "creator_type": "author", "first_name": "Hiroko", "last_name": "Morimoto", "name": null }, { "creator_type": "author", "first_name": "Tianjiao", "last_name": "Liu", "name": null }, { "creator_type": "author", "first_name": "Tohru", "last_name": "Yamamori", "name": null }, { "creator_type": "author", "first_name": "Tomokazu", "last_name": "Yamasaki", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Shinohara", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.stemcr.2025.102602" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "40816273" } }, "mesh": [ { "descriptor": "Adult Germline Stem Cells", "descriptor_ui": "D000072956", "major_topic": true }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Apoptosis", "descriptor_ui": "D017209", "major_topic": false }, { "descriptor": "Cryopreservation", "descriptor_ui": "D015925", "major_topic": true }, { "descriptor": "DNA Damage", "descriptor_ui": "D004249", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Space Flight", "descriptor_ui": "D013026", "major_topic": true }, { "descriptor": "Spermatogonia", "descriptor_ui": "D013093", "major_topic": true } ], "publication": { "conference_name": null, "date": "2025 Aug 5", "date_precision": "day", "issue": "", "normalized_date": "2025-08-05", "pages": "102602", "proceedings_title": null, "publisher": "", "title": "Stem cell reports", "volume": "", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Germline transmission of cryopreserved mouse spermatogonial stem cells maintained on the International Space Station.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "In response to environmental changes, chloroplasts, the cellular organelles responsible for photosynthesis, undergo intracellular repositioning, a phenomenon known as chloroplast movement. Observing chloroplast movement within leaf tissues remains technically challenging in leaves consisting of multiple cell layers, where light scattering and absorption hinder deep tissue visualization. This limitation has been particularly problematic when analyzing chloroplast movement in the mesophyll cells of C(4) plants, which possess two distinct types of concentrically arranged photosynthetic cells. In response to stress stimuli, mesophyll chloroplasts aggregate toward the inner bundle sheath cells. However, conventional methods have not been able to observe these chloroplast dynamics over time in living cells, making it difficult to assess the influence of adjacent bundle sheath cells on this movement. Here, we present a protocol for live leaf section imaging that enables long-term and detailed observation of chloroplast movement in internal leaf tissues without chemical fixation. In this method, a leaf blade section prepared either using a vibratome or by hand was placed in a groove made of a silicone rubber sheet attached to a glass slide for microscopic observation. This technique allows for the quantitative tracking of chloroplast movement relative to the surrounding cells. In addition, by adjusting the sectioning angle and thickness of the unfixed leaf sections, it is possible to selectively inactivate specific cell types based on their size and shape differences. This protocol enables the investigation of the intercellular interactions involved in chloroplast dynamics in leaf tissues. Key features * Thin leaf sections prepared while still alive enable prolonged microscopic observation of chloroplast movement within the leaf tissue. * Selective cell inactivation can be achieved by adjusting the slice thickness and angle. * This method is applicable to a wide range of plant species.", "classifications": [ { "id": "Sato", "label": "Group Sato", "parent": "Tsuchiya", "type": "group" }, { "id": "Tsuchiya", "label": "Team Tsuchiya", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yuta", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Takao", "last_name": "Oi", "name": null }, { "creator_type": "author", "first_name": "Yoshikatsu", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Mitsutaka", "last_name": "Taniguchi", "name": null } ], "identifiers": { "doi": { "normalized": "10.21769/bioprotoc.5404" }, "pmcid": { "normalized": "PMC12336861" }, "pmid": { "normalized": "40799481" } }, "mesh": [], "publication": { "conference_name": null, "date": "2025 Aug 5", "date_precision": "day", "issue": "15", "normalized_date": "2025-08-05", "pages": "e5404", "proceedings_title": null, "publisher": "", "title": "Bio-protocol", "volume": "15", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Live Leaf-Section Imaging for Visualizing Intracellular Chloroplast Movement and Analyzing Cell-Cell Interactions.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "In endometrial cancer, detection of oncogenic mutations in the polymerase epsilon (POLE) gene is crucial for accurate staging according to the 2023 International Federation of Gynecology and Obstetrics classification and for minimizing overtreatment. However, POLE sequencing is expensive, time-consuming, and often inaccessible in settings without specialized equipment. We developed a novel multiplex kit for the detection of POLE mutations using a Luminex (xMAP) assay in a single reaction. The aim of this study was to evaluate the accuracy of the multiplex kit for routine clinical samples and compare it with that of conventional next-generation sequencing (NGS). Hysterectomy specimens and endometrial biopsies were collected at the National Cancer Center Hospital between 1999 and 2023. Genomic DNA was extracted from formalin-fixed, paraffin-embedded tissues. Both the Luminex (xMAP)-based multiplex kit and NGS targeting all POLE exons were used. Concordance was assessed using Cohen's kappa. Of the 502 samples, 432 were hysterectomy specimens and 70 were biopsies. In the surgical samples, both the Luminex (xMAP)-based kit and NGS detected 52 POLE mutations (12.0%) with perfect concordance (kappa = 1.000). In the biopsies, 33 POLE mutations were identified using both methods, with complete concordance. Notably, the Luminex (xMAP)-based kit successfully analyzed all 28 samples that failed NGS quality control and detected four cases with POLE mutations. The Luminex (xMAP)-based kit demonstrates high concordance with NGS for the detection of POLE mutations. With further external validation, this kit could become a reliable and accessible alternative to NGS.", "classifications": [ { "id": "Hamamoto", "label": "Group Hamamoto", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Mayumi Kobayashi", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Takayuki", "last_name": "Kawai", "name": null }, { "creator_type": "author", "first_name": "Hideki", "last_name": "Okada", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Kondo", "name": null }, { "creator_type": "author", "first_name": "Tetsuro", "last_name": "Shiraishi", "name": null }, { "creator_type": "author", "first_name": "Maiko", "last_name": "Yamaguchi", "name": null }, { "creator_type": "author", "first_name": "Daiki", "last_name": "Higuchi", "name": null }, { "creator_type": "author", "first_name": "Masaaki", "last_name": "Komatsu", "name": null }, { "creator_type": "author", "first_name": "Ryuji", "last_name": "Hamamoto", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Matumoto", "name": null }, { "creator_type": "author", "first_name": "Yasuhisa", "last_name": "Terao", "name": null }, { "creator_type": "author", "first_name": "Tomoyasu", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Kohno", "name": null }, { "creator_type": "author", "first_name": "Mitsuya", "last_name": "Ishikawa", "name": null }, { "creator_type": "author", "first_name": "Kouya", "last_name": "Shiraishi", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Yoshida", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/s00428-025-04204-4" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "40760194" } }, "mesh": [], "publication": { "conference_name": null, "date": "2025 Aug 4", "date_precision": "day", "issue": "", "normalized_date": "2025-08-04", "pages": "", "proceedings_title": null, "publisher": "", "title": "Virchows Archiv : an international journal of pathology", "volume": "", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Comparison between a Luminex-based multiplex kit with a sequence-specific oligonucleotide probe and next-generation sequencing for the detection of POLE oncogenic mutations in endometrial cancer.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "We present the results of Raman imaging of molecular crowding environments in a living cell and a liquid droplet formed by liquid-liquid phase separation. Using the Raman band of water as an internal intensity standard, we propose an in situ quantification method for evaluating biomolecular concentrations. Based on these concentration measurements, intracellular crowding environments can be quantitatively assessed. A single liquid droplet in a buffer solution is found to have a very high biomolecular concentration, exceeding a few millimolar concentrations, and the concentration within a droplet varies depending on the surrounding environment. The biomolecular concentration in a droplet increases as conditions facilitate droplet formation, and we propose a model in which changes in the surrounding environment lead to the formation of dense droplets, which subsequently transform into aggregates. Concentration quantification in a single droplet was also performed in a living cell, demonstrating that the biomolecular concentration in a droplet is not much different from that in the surrounding intracellular environment. This result indicates that within a droplet in a cell, certain molecules are highly concentrated, while other molecules are excluded, and the overall concentration is comparable to that of the surrounding intracellular environment. The droplet formation within a cell can be regarded as a redistribution of biomolecules constituting a molecular crowding environment.", "classifications": [ { "id": "JPMJCR2024", "label": "JPMJCR2024", "researcher": "Motohiro Nishida", "type": "grant" }, { "id": "Nakabayashi", "label": "Group Nakabayashi", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Group Nishida", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Takakazu", "last_name": "Nakabayashi", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Tahara", "name": null }, { "creator_type": "author", "first_name": "Shinji", "last_name": "Kajimoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/acs.jpcb.5c02288" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "40757639" } }, "mesh": [ { "descriptor": "Phase Separation", "descriptor_ui": "D000095496", "major_topic": false }, { "descriptor": "Spectrum Analysis, Raman", "descriptor_ui": "D013059", "major_topic": true }, { "descriptor": "Water", "descriptor_ui": "D014867", "major_topic": false } ], "publication": { "conference_name": null, "date": "2025 Aug 4", "date_precision": "day", "issue": "", "normalized_date": "2025-08-04", "pages": "", "proceedings_title": null, "publisher": "", "title": "The journal of physical chemistry. B", "volume": "", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Liquid-Liquid Phase Separation from the Viewpoint of Molecular Crowding Environment: A Raman Imaging Study.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "In the liver, hepatocyte death occurs during the regeneration process following injury. While hepatocyte death triggers regeneration through hepatocyte proliferation in the non-steatotic liver, it impairs this process in the steatotic liver. Both the number and mode of hepatocyte death during regeneration change in the steatotic liver, affecting regeneration and thereby contributing to the progression of acute liver injury and metabolic dysfunction-associated steatotic liver disease (MASLD). Apoptosis, a non-inflammatory mode of cell death, predominantly occurs during liver regeneration. As hepatic steatosis progresses, sporadic and scattered apoptotic cell death increases, leading to delayed regeneration. In severe steatotic livers undergoing regeneration, the mode of cell death shifts to pro-inflammatory necroptosis. This transition leads to inflammation around the dead hepatocytes, resulting in zonal hepatocyte death and further impairing regeneration, thus exacerbating acute liver injury and MASLD. The integrated stress response (ISR), mediated by phosphorylation of the alpha-subunit of eukaryotic initiation factor 2 (eIF2alpha), plays a crucial role in regulating hepatocyte death during steatotic liver regeneration. The ISR-induced transcription factor C/EBP homologous protein (CHOP) promotes apoptosis, thereby delaying regeneration. When ISR is further enhanced, activating transcription factor 3 (ATF3) is upregulated, inducing the expression of receptor-interacting protein kinase 3 (RIPK3), which shifts cell death mode from apoptosis to necroptosis. While treatments for MASLD targeting apoptosis have shown limited success, future therapies targeting necroptosis and its regulatory molecules may provide novel therapeutic strategies.", "classifications": [ { "id": "JPMJCR2123", "label": "JPMJCR2123", "researcher": "Shinya Kuroda", "type": "grant" }, { "id": "Inaba", "label": "Group Inaba", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Group Kuroda", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yuka", "last_name": "Inaba", "name": null }, { "creator_type": "author", "first_name": "Kohsuke", "last_name": "Tsuchiya", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Inoue", "name": null } ], "identifiers": { "doi": { "normalized": "10.1507/endocrj.ej25-0168" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "40738687" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Apoptosis", "descriptor_ui": "D017209", "major_topic": true }, { "descriptor": "Cell Death", "descriptor_ui": "D016923", "major_topic": false }, { "descriptor": "Fatty Liver", "descriptor_ui": "D005234", "major_topic": true }, { "descriptor": "Hepatocytes", "descriptor_ui": "D022781", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Liver", "descriptor_ui": "D008099", "major_topic": true }, { "descriptor": "Liver Regeneration", "descriptor_ui": "D008115", "major_topic": false }, { "descriptor": "Necroptosis", "descriptor_ui": "D000079302", "major_topic": true } ], "publication": { "conference_name": null, "date": "2025 Jul 31", "date_precision": "day", "issue": "", "normalized_date": "2025-07-31", "pages": "", "proceedings_title": null, "publisher": "", "title": "Endocrine journal", "volume": "", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Shifting cell death modes in hepatic steatosis: from apoptosis to necroptosis.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The cell cycle is a highly coordinated process governed by cyclin-bound cyclin-dependent kinases (CDKs). While the interaction between cyclin and CDK are well-documented, the dissociation constants (Kd) between specific cyclin-CDK pairs within living cells remain poorly understood. Fluorescence cross-correlation spectroscopy (FCCS) enables the quantification of the Kd, but challenges remain in selecting an optimal pair of fluorescent molecules for FCCS in a living cell. In this study, we demonstrate that mNeonGreen and phycocyanobilin-bound miRFP670 represent a suitable pair for FCCS in living cells from the viewpoint of high photostability and low bleed-through. This fluorescent protein pair enables us to measure the Kd values of the cyclin-dependent kinase Cdc2 and B-type cyclin Cdc13 in fission yeast cells. Moreover, we roughly estimated the Kd values for 36 cyclin-CDK complexes, formed by 9 distinct cyclins and 4 CDKs, in mammalian cells, including unconventional cyclin-CDK pairs. These measurements suggest potential versatility of cyclin-CDK binding in cell cycle progression, with implications for understanding cell cycle regulation in both fission yeast and higher eukaryotes.", "classifications": [ { "id": "Mochizuki", "label": "Group Mochizuki", "parent": "Eiraku", "type": "group" }, { "id": "Eiraku", "label": "Team Eiraku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Aika", "last_name": "Toyama", "name": null }, { "creator_type": "author", "first_name": "Yuhei", "last_name": "Goto", "name": null }, { "creator_type": "author", "first_name": "Yuhei", "last_name": "Yamauchi", "name": null }, { "creator_type": "author", "first_name": "Hironori", "last_name": "Sugiyama", "name": null }, { "creator_type": "author", "first_name": "Yohei", "last_name": "Kondo", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Mochizuki", "name": null }, { "creator_type": "author", "first_name": "Kazuhiro", "last_name": "Aoki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1242/jcs.263921" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "40741734" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Cycle", "descriptor_ui": "D002453", "major_topic": false }, { "descriptor": "Cyclin-Dependent Kinases", "descriptor_ui": "D018844", "major_topic": true }, { "descriptor": "Cyclins", "descriptor_ui": "D016213", "major_topic": true }, { "descriptor": "Green Fluorescent Proteins", "descriptor_ui": "D049452", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Luminescent Proteins", "descriptor_ui": "D008164", "major_topic": true }, { "descriptor": "Protein Binding", "descriptor_ui": "D011485", "major_topic": false }, { "descriptor": "Schizosaccharomyces", "descriptor_ui": "D012568", "major_topic": false }, { "descriptor": "Schizosaccharomyces pombe Proteins", "descriptor_ui": "D029702", "major_topic": false }, { "descriptor": "Spectrometry, Fluorescence", "descriptor_ui": "D013050", "major_topic": false } ], "publication": { "conference_name": null, "date": "2025 Jul 31", "date_precision": "day", "issue": "", "normalized_date": "2025-07-31", "pages": "jcs.263921", "proceedings_title": null, "publisher": "", "title": "Journal of cell science", "volume": "", "year": 2025 }, "ssbd": { "database": [], "repository": [ "ssbd-repos-000455" ] }, "title": "Quantification of Cyclin-CDK dissociation constants using FCCS with green and near-infrared fluorescent proteins.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: The potassium voltage-gated channel subfamily Q member 1 (KCNQ1) gene has recently received much attention as a candidate susceptibility gene for type 2 diabetes mellitus, especially in Asian populations. We previously reported that Kcnq1 mutant mice exhibit reduced insulin secretion and hyperglycemia due to a decrease in pancreatic beta-cell mass. Through in vivo and in vitro analyses, we ascertained that this mechanism is the result of the downregulation of the non-coding RNA 'Kcnq1ot1,' which is expressed in the paternal allele of the Kcnq1 gene region, causing an increase in the expression of the cell cycle inhibitor cyclin dependent kinase inhibitor 1C (Cdkn1c). It was found that decreased Kcnq1ot1 expression resulted in pancreatic beta-cell failure; however, the degree of pancreatic beta-cell volume reduction was not severe. METHODS: We induced obesity in Kcnq1ot1 truncation mice by feeding them a high-fat diet and evaluated pancreatic beta-cell mass. RESULTS: In the present study, we reveal that CCAAT/enhancer binding protein beta (C/EBPbeta), which is expressed at higher levels in pancreatic beta-cells in obese individuals, further increases the expression of Cdkn1c, which is upregulated by the Kcnq1 gene mutation. We found that simultaneous Cdkn1c hypomethylation and C/EBPbeta overexpression in pancreatic beta-cells causes a synergistic decrease in pancreatic beta-cell mass. CONCLUSION: This finding suggests that the synergistic effect of genetic factors such as Kcnq1 gene mutations and environmental factors such as obesity and overeating, which lead to increased expression of C/EBPbeta, contribute to the regulation of pancreatic beta-cell mass. This study is the first to show that the Kcnq1 gene is related to pancreatic beta-cell mass through genetic-environment interactions.", "classifications": [ { "id": "Inaba", "label": "Group Inaba", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Shun-Ichiro", "last_name": "Asahara", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Inoue", "name": null }, { "creator_type": "author", "first_name": "Yuka", "last_name": "Ihara", "name": null }, { "creator_type": "author", "first_name": "Kyoko", "last_name": "Teruyama", "name": null }, { "creator_type": "author", "first_name": "Asuka", "last_name": "Imai", "name": null }, { "creator_type": "author", "first_name": "Chisako", "last_name": "Hara", "name": null }, { "creator_type": "author", "first_name": "Mizuki", "last_name": "Hara", "name": null }, { "creator_type": "author", "first_name": "Masako", "last_name": "Seike", "name": null }, { "creator_type": "author", "first_name": "Aisha", "last_name": "Yokoi", "name": null }, { "creator_type": "author", "first_name": "Nozomi", "last_name": "Kido", "name": null }, { "creator_type": "author", "first_name": "Hirotaka", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Ayumi", "last_name": "Kanno", "name": null }, { "creator_type": "author", "first_name": "Yuka", "last_name": "Inaba", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Go", "last_name": "Shioi", "name": null }, { "creator_type": "author", "first_name": "Maki", "last_name": "Kimura-Koyanagi", "name": null }, { "creator_type": "author", "first_name": "Michihiro", "last_name": "Matsumoto", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Inoue", "name": null }, { "creator_type": "author", "first_name": "Keiichi I.", "last_name": "Nakayama", "name": null }, { "creator_type": "author", "first_name": "Wataru", "last_name": "Ogawa", "name": null }, { "creator_type": "author", "first_name": "Masato", "last_name": "Kasuga", "name": null }, { "creator_type": "author", "first_name": "Yoshiaki", "last_name": "Kido", "name": null } ], "identifiers": { "doi": { "normalized": "10.4093/dmj.2024.0790" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "40734497" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "CCAAT-Enhancer-Binding Protein-beta", "descriptor_ui": "D022782", "major_topic": false }, { "descriptor": "Cyclin-Dependent Kinase Inhibitor p57", "descriptor_ui": "D050761", "major_topic": false }, { "descriptor": "Diabetes Mellitus, Type 2", "descriptor_ui": "D003924", "major_topic": true }, { "descriptor": "Diet, High-Fat", "descriptor_ui": "D059305", "major_topic": false }, { "descriptor": "Gene Deletion", "descriptor_ui": "D017353", "major_topic": false }, { "descriptor": "Gene Expression", "descriptor_ui": "D015870", "major_topic": false }, { "descriptor": "Gene-Environment Interaction", "descriptor_ui": "D059647", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Insulin-Secreting Cells", "descriptor_ui": "D050417", "major_topic": true }, { "descriptor": "KCNQ1 Potassium Channel", "descriptor_ui": "D051657", "major_topic": false }, { "descriptor": "Methylation", "descriptor_ui": "D008745", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": false }, { "descriptor": "Obesity", "descriptor_ui": "D009765", "major_topic": false }, { "descriptor": "Pancreas", "descriptor_ui": "D010179", "major_topic": true }, { "descriptor": "Promoter Regions, Genetic", "descriptor_ui": "D011401", "major_topic": false }, { "descriptor": "RNA, Long Noncoding", "descriptor_ui": "D062085", "major_topic": false } ], "publication": { "conference_name": null, "date": "2025 Jul 30", "date_precision": "day", "issue": "", "normalized_date": "2025-07-30", "pages": "", "proceedings_title": null, "publisher": "", "title": "Diabetes & metabolism journal", "volume": "", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "High-Fat Diet-Fed Kcnq1 Mutant Mice Have Reduced Pancreatic beta-Cell Mass via Gene-Environment Interaction.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "AIMS: Hepatic differentiation in lung adenocarcinomas, including hepatoid adenocarcinomas, is rare. We encountered a case of lung adenocarcinoma with distinct cytoplasmic TTF-1 expression, which is characteristic of neoplastic and non-neoplastic hepatocytes, and confirmed positivity for hepatic markers, including hepatocyte paraffin 1 (HepPar1) and glypican-3. This prompted a retrospective analysis of hepatic differentiation in lung adenocarcinoma. METHODS AND RESULTS: Among 123 surgically resected lung tumours, 1 adenocarcinoma (0.1%) showed positivity for HepPar1, hepatocyte nuclear factor 4-alpha and cytoplasmic TTF-1, with heterogeneous expression confined to part of the tumour. This heterogeneity led us to investigate expressional variations in hepatic differentiation during the clinical course. In an analysis of 992 patients with at least two specimens collected during treatment, hepatic differentiation, identified via HepPar1 expression, was present in at least one specimen in 8 patients, with cytoplasmic TTF-1 expression used as a reference. Notably, in 7 of 8 patients, hepatic differentiation emerged or expanded with disease progression, suggesting its dynamic nature and potential association with disease progression. CONCLUSIONS: The observed variability in hepatic marker expression over the clinical course suggests that hepatic differentiation may be a dynamic process influenced by treatment or disease progression, rather than a static characteristic of a distinct tumour entity. In routine practice, hepatic differentiation is tracked using cytoplasmic TTF-1 expression.", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Chihiro", "last_name": "Takemura", "name": null }, { "creator_type": "author", "first_name": "Satsuki", "last_name": "Kishikawa", "name": null }, { "creator_type": "author", "first_name": "Jumpei", "last_name": "Kashima", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Igaki", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Kusumoto", "name": null }, { "creator_type": "author", "first_name": "Yuichiro", "last_name": "Ohe", "name": null }, { "creator_type": "author", "first_name": "Shun-Ichi", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/his.15517" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "40731369" } }, "mesh": [ { "descriptor": "Adenocarcinoma", "descriptor_ui": "D000230", "major_topic": true }, { "descriptor": "Adenocarcinoma of Lung", "descriptor_ui": "D000077192", "major_topic": false }, { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Aged, 80 and over", "descriptor_ui": "D000369", "major_topic": false }, { "descriptor": "Antigens, Neoplasm", "descriptor_ui": "D000951", "major_topic": false }, { "descriptor": "Biomarkers, Tumor", "descriptor_ui": "D014408", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Hepatocytes", "descriptor_ui": "D022781", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Lung Neoplasms", "descriptor_ui": "D008175", "major_topic": true }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Retrospective Studies", "descriptor_ui": "D012189", "major_topic": false }, { "descriptor": "Transcription Factors", "descriptor_ui": "D014157", "major_topic": false } ], "publication": { "conference_name": null, "date": "2025 Jul 29", "date_precision": "day", "issue": "", "normalized_date": "2025-07-29", "pages": "", "proceedings_title": null, "publisher": "", "title": "Histopathology", "volume": "", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Dynamic nature of hepatic differentiation in lung adenocarcinoma.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The regulation of biological functions is achieved through the modulation of biochemical reaction network dynamics. The diversity of cell states and the transitions between them have been interpreted as bifurcations in these dynamics. However, due to the complexity of networks and limited knowledge of reaction kinetics, bifurcation behaviors in biological systems remain largely underexplored. To address this, we developed a mathematical method, Structural Bifurcation Analysis (SBA), which decomposes the system into substructures and determines important aspects of bifurcation behaviors-such as substructures responsible for bifurcation conditions, bifurcation-inducing parameters, and bifurcating variables-solely from network topology. We establish a direct relationship between SBA and classical bifurcation analysis, enabling the study of systems even in the presence of conserved quantities. Additionally, we provide a step-by-step bifurcation analysis for general use. We applied our method to the macrophage M1/M2 polarization system. Our analysis reveals that the network structure strongly constrains possible patterns of polarization. We also clarify the dependency of the M1/M2 balance on gene expression levels and predict the emergence of intermediate polarization patterns under gene deletions, including SOCS3, which are experimentally testable.", "classifications": [ { "id": "JPMJCR1922", "label": "JPMJCR1922", "researcher": "Mototsugu Eiraku", "type": "grant" }, { "id": "Eiraku", "label": "Group Eiraku", "parent": "Eiraku", "type": "group" }, { "id": "Mochizuki", "label": "Group Mochizuki", "parent": "Eiraku", "type": "group" }, { "id": "Eiraku", "label": "Team Eiraku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yong-Jin", "last_name": "Huang", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Okada", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Mochizuki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41598-025-10688-6" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "40730575" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Macrophages", "descriptor_ui": "D008264", "major_topic": false }, { "descriptor": "Models, Biological", "descriptor_ui": "D008954", "major_topic": true }, { "descriptor": "Suppressor of Cytokine Signaling 3 Protein", "descriptor_ui": "D000071223", "major_topic": false } ], "publication": { "conference_name": null, "date": "2025 Jul 29", "date_precision": "day", "issue": "1", "normalized_date": "2025-07-29", "pages": "27596", "proceedings_title": null, "publisher": "", "title": "Scientific reports", "volume": "15", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Uncovering bifurcation behaviors of biochemical reaction systems from network topology.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Arabidopsis thaliana zygotes form a circumferential cortical microtubule (CMT) band that moves upward along the longitudinal axis of the cylindrical cell; however, how and why this CMT band moves remain unknown. Based on several recently proposed feedback mechanisms of CMT reorientation, we hypothesized that a directional cue (DC) changes CMT orientation. We constructed an agent-based simulation model with a DC to observe what happens during CMT formation using different parameters. We determined that the output CMT band can become larger than the input DC zone and identified two types of self-organization processes depending on the parameters used. Furthermore, using well-defined parameters that form a static CMT band, we artificially changed the position of the input DC zone, revealing that CMT band movement requires a DC to move at an appropriate speed.", "classifications": [ { "id": "JPMJCR2121", "label": "JPMJCR2121", "researcher": "Minako Ueda", "type": "grant" }, { "id": "Tsugawa", "label": "Group Tsugawa", "parent": "Ueda", "type": "group" }, { "id": "Ueda", "label": "Group Ueda", "parent": "Ueda", "type": "group" }, { "id": "Ueda", "label": "Team Ueda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Tomonobu", "last_name": "Nonoyama", "name": null }, { "creator_type": "author", "first_name": "Zichen", "last_name": "Kang", "name": null }, { "creator_type": "author", "first_name": "Hikari", "last_name": "Matsumoto", "name": null }, { "creator_type": "author", "first_name": "Sakumi", "last_name": "Nakagawa", "name": null }, { "creator_type": "author", "first_name": "Minako", "last_name": "Ueda", "name": null }, { "creator_type": "author", "first_name": "Satoru", "last_name": "Tsugawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41598-025-11078-8" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "40721711" } }, "mesh": [ { "descriptor": "Arabidopsis", "descriptor_ui": "D017360", "major_topic": true }, { "descriptor": "Computer Simulation", "descriptor_ui": "D003198", "major_topic": false }, { "descriptor": "Microtubules", "descriptor_ui": "D008870", "major_topic": true }, { "descriptor": "Models, Biological", "descriptor_ui": "D008954", "major_topic": false }, { "descriptor": "Zygote", "descriptor_ui": "D015053", "major_topic": true } ], "publication": { "conference_name": null, "date": "2025 Jul 28", "date_precision": "day", "issue": "1", "normalized_date": "2025-07-28", "pages": "25787", "proceedings_title": null, "publisher": "", "title": "Scientific reports", "volume": "15", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Agent-based simulation of cortical microtubule band movement in arabidopsis zygotes.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Venus flytrap (Dionaea muscipula) leaves exhibit an exceptionally rapid closing motion that occurs within one second. The rapid closure of outwardly curved leaves is thought to be driven by snap-buckling instability-a rapid transition of an elastic system from one state to another. However, the ability of leaves that do not curve outward to also close suggests that the mechanics of leaf closure are complex and need to be understood using three-dimensional (3D) kinematics. We therefore developed a 3D reconstruction method to quantify the curvatures and displacements of leaf blades using two high-speed cameras. We then reconstructed a 3D surface mesh of the leaf, which revealed that the changes in curvature are spatiotemporally heterogeneous. We inferred the stretching and curvature elastic energies of the reconstructed surface, determining that the mechanical forces associated with in-plane deformation become significant in the peripheral regions of the leaf. This was true among different samples; however, the components of the energy profiles varied for each sample. The novelty of this study is that we could infer the elastic energy and the corresponding mechanical forces during closing motion. Our mechanical inference method will be useful for examining the deformation processes of various curved plant structures.", "classifications": [ { "id": "JPMJCR2121", "label": "JPMJCR2121", "researcher": "Minako Ueda", "type": "grant" }, { "id": "Tsugawa", "label": "Group Tsugawa", "parent": "Ueda", "type": "group" }, { "id": "Ueda", "label": "Group Ueda", "parent": "Ueda", "type": "group" }, { "id": "Ueda", "label": "Team Ueda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Satoru", "last_name": "Tsugawa", "name": null }, { "creator_type": "author", "first_name": "Hiroki", "last_name": "Asakawa", "name": null }, { "creator_type": "author", "first_name": "Michiko", "last_name": "Hirata", "name": null }, { "creator_type": "author", "first_name": "Tomonobu", "last_name": "Nonoyama", "name": null }, { "creator_type": "author", "first_name": "Zichen", "last_name": "Kang", "name": null }, { "creator_type": "author", "first_name": "Masatsugu", "last_name": "Toyota", "name": null }, { "creator_type": "author", "first_name": "Hiraku", "last_name": "Suda", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41598-025-10638-2" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "40721427" } }, "mesh": [ { "descriptor": "Biomechanical Phenomena", "descriptor_ui": "D001696", "major_topic": false }, { "descriptor": "Droseraceae", "descriptor_ui": "D031257", "major_topic": true }, { "descriptor": "Imaging, Three-Dimensional", "descriptor_ui": "D021621", "major_topic": true }, { "descriptor": "Motion", "descriptor_ui": "D009038", "major_topic": false }, { "descriptor": "Plant Leaves", "descriptor_ui": "D018515", "major_topic": true } ], "publication": { "conference_name": null, "date": "2025 Jul 28", "date_precision": "day", "issue": "1", "normalized_date": "2025-07-28", "pages": "24860", "proceedings_title": null, "publisher": "", "title": "Scientific reports", "volume": "15", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Inference of mechanical forces through 3D reconstruction of the closing motion in venus flytrap leaves.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "INTRODUCTION: TNM staging systems create prognostic categories by anatomic extent of disease. Whether therapeutically important molecular alterations in NSCLC augment the prognostic information of TNM staging is unclear. To study this, we analyzed molecular data from the ninth edition of the lung cancer staging system. METHODS: Eligible patients were diagnosed between 2011 and 2019. Analysis was restricted to the following three genes for reliable statistical analyses: EGFR mutations (L858R, exon 19 deletion), ALK fusions, and KRAS mutations (codons 12, 13, or 61). Overall survival (OS) was calculated by the Kaplan-Meier method, and differences in OS were assessed by Cox proportional hazard regression models. RESULTS: A total of 20,580 patients had tumors with molecular data (EGFR = 16,497, ALK = 11,546, KRAS = 2909 patients). EGFR mutations were found in 5428 (32.9%), ALK fusions in 723 (6.3%), and KRAS mutations in 890 (30.6%) tumors. OS was significantly better across all TNM stages among patients with EGFR-mutated tumors and patients with stage IV ALK fusion-positive tumors, whereas patients with stage I KRAS-mutated tumors had significantly worse OS. Multivariable analyses confirmed the OS associations with EGFR-mutated tumors (stage I hazard ratio [HR] = 0.79, stage II HR = 0.71, stage III HR = 0.67, stage IV HR = 0.49) and stage IV ALK fusion-positive tumors (HR = 0.56). CONCLUSIONS: Patients with EGFR-mutated tumors had improved OS regardless of stage, whereas an OS benefit was found in stage IV patients with ALK-positive tumors. In the tenth edition, we will evaluate the systematic integration of molecular biomarkers and treatment to refine prognostication for molecular subsets of NSCLC.", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "David P.", "last_name": "Carbone", "name": null }, { "creator_type": "author", "first_name": "Fred R.", "last_name": "Hirsch", "name": null }, { "creator_type": "author", "first_name": "Raymond Uyiosa", "last_name": "Osarogiagbon", "name": null }, { "creator_type": "author", "first_name": "Katherine K.", "last_name": "Nishimura", "name": null }, { "creator_type": "author", "first_name": "Ming Sound", "last_name": "Tsao", "name": null }, { "creator_type": "author", "first_name": "William D.", "last_name": "Travis", "name": null }, { "creator_type": "author", "first_name": "Dawei", "last_name": "Yang", "name": null }, { "creator_type": "author", "first_name": "Soo-Ryum", "last_name": "Yang", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null }, { "creator_type": "author", "first_name": "Luiz Henrique", "last_name": "Araujo", "name": null }, { "creator_type": "author", "first_name": "Frank", "last_name": "Detterbeck", "name": null }, { "creator_type": "author", "first_name": "Kendra J.", "last_name": "Lechtenberg", "name": null }, { "creator_type": "author", "first_name": "Eric", "last_name": "Lim", "name": null }, { "creator_type": "author", "first_name": "Philip C.", "last_name": "Mack", "name": null }, { "creator_type": "author", "first_name": "Jose-Maria", "last_name": "Matilla", "name": null }, { "creator_type": "author", "first_name": "Luis M.", "last_name": "Montuenga", "name": null }, { "creator_type": "author", "first_name": "Andrew G.", "last_name": "Nicholson", "name": null }, { "creator_type": "author", "first_name": "Kenichi", "last_name": "Suda", "name": null }, { "creator_type": "author", "first_name": "Ricardo M.", "last_name": "Terra", "name": null }, { "creator_type": "author", "first_name": "Ramon", "last_name": "Rami-Porta", "name": null }, { "creator_type": "author", "first_name": "Hisao", "last_name": "Asamura", "name": null }, { "creator_type": "author", "first_name": "Valerie", "last_name": "Rusch", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.jtho.2025.06.025" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "40920144" } }, "mesh": [ { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Anaplastic Lymphoma Kinase", "descriptor_ui": "D000077548", "major_topic": false }, { "descriptor": "Carcinoma, Non-Small-Cell Lung", "descriptor_ui": "D002289", "major_topic": true }, { "descriptor": "Databases, Factual", "descriptor_ui": "D016208", "major_topic": false }, { "descriptor": "ErbB Receptors", "descriptor_ui": "D066246", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Follow-Up Studies", "descriptor_ui": "D005500", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Lung Neoplasms", "descriptor_ui": "D008175", "major_topic": true }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": false }, { "descriptor": "Neoplasm Staging", "descriptor_ui": "D009367", "major_topic": false }, { "descriptor": "Prognosis", "descriptor_ui": "D011379", "major_topic": false }, { "descriptor": "Proto-Oncogene Proteins p21(ras)", "descriptor_ui": "D016283", "major_topic": false }, { "descriptor": "Survival Rate", "descriptor_ui": "D015996", "major_topic": false } ], "publication": { "conference_name": null, "date": "2025 Jul 28", "date_precision": "day", "issue": "", "normalized_date": "2025-07-28", "pages": "S1556-0864(25)00813-5", "proceedings_title": null, "publisher": "", "title": "Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer", "volume": "", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "The International Association for the Study of Lung Cancer Staging Project: The Impact of Common Molecular Alterations on Overall Survival in NSCLC in Initial Analyses of the IASLC Ninth Edition Staging Database.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Adipose tissue remodels via hypertrophy or hyperplasia in response to nutrient status, but the mechanisms governing these expansion modes remain unclear. Here, we identify a nutrient-sensitive epigenetic circuit linking glucose metabolism to chromatin remodeling during adipogenesis. Upon glucose stimulation, alpha-ketoglutarate (alpha-KG) accumulates in the nucleus and activates the histone demethylase JMJD1A to remove repressive histone H3 lysine 9 dimethylation (H3K9me2) marks at glycolytic and adipogenic gene loci, including Pparg. JMJD1A is recruited to pre-marked promoter chromatin via nuclear factor IC (NFIC), enabling carbohydrate-responsive element-binding protein (ChREBP) binding and transcriptional activation. This feedforward mechanism couples nutrient flux to chromatin accessibility and gene expression. In vivo, JMJD1A is essential for de novo adipogenesis and hyperplastic expansion in visceral fat under nutrient excess. JMJD1A deficiency impairs hyperplasia, exacerbates adipocyte hypertrophy, and induces local inflammation. These findings define a glucose-alpha-KG-JMJD1A-ChREBP axis regulating depot-specific adipogenesis and uncover a chromatin-based mechanism by which glucose metabolism governs adaptive adipose tissue remodeling.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Chenxu", "last_name": "Yang", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Arai", "name": null }, { "creator_type": "author", "first_name": "Eko Fuji", "last_name": "Ariyanto", "name": null }, { "creator_type": "author", "first_name": "Ji", "last_name": "Zhang", "name": null }, { "creator_type": "author", "first_name": "Debby Mirani", "last_name": "Lubis", "name": null }, { "creator_type": "author", "first_name": "Ryo", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Shiyu", "last_name": "Xie", "name": null }, { "creator_type": "author", "first_name": "Mio", "last_name": "Nitta", "name": null }, { "creator_type": "author", "first_name": "Fuka", "last_name": "Kawashima", "name": null }, { "creator_type": "author", "first_name": "Tomofumi", "last_name": "Ishitsuka", "name": null }, { "creator_type": "author", "first_name": "Chaoran", "last_name": "Yang", "name": null }, { "creator_type": "author", "first_name": "Tomohiro", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Tetsuro", "last_name": "Komatsu", "name": null }, { "creator_type": "author", "first_name": "Hina", "last_name": "Sagae", "name": null }, { "creator_type": "author", "first_name": "Hitomi", "last_name": "Jin", "name": null }, { "creator_type": "author", "first_name": "Hiroki", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Eri", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Yuchen", "last_name": "Wei", "name": null }, { "creator_type": "author", "first_name": "Bohao", "last_name": "Liu", "name": null }, { "creator_type": "author", "first_name": "Hyunmi", "last_name": "Choi", "name": null }, { "creator_type": "author", "first_name": "Youichiro", "last_name": "Wada", "name": null }, { "creator_type": "author", "first_name": "Toshiya", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Tsuyoshi", "last_name": "Osawa", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Kimura", "name": null }, { "creator_type": "author", "first_name": "Tatsuhiko", "last_name": "Kodama", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Aburatani", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Tachibana", "name": null }, { "creator_type": "author", "first_name": "Yoichi", "last_name": "Shinkai", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Inagaki", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Timothy F.", "last_name": "Osborne", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Yoneshiro", "name": null }, { "creator_type": "author", "first_name": "Yoshihiro", "last_name": "Matsumura", "name": null }, { "creator_type": "author", "first_name": "Juro", "last_name": "Sakai", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.celrep.2025.116060" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "40720241" } }, "mesh": [ { "descriptor": "Adipocytes", "descriptor_ui": "D017667", "major_topic": false }, { "descriptor": "Adipogenesis", "descriptor_ui": "D050156", "major_topic": true }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Chromatin", "descriptor_ui": "D002843", "major_topic": false }, { "descriptor": "Chromatin Assembly and Disassembly", "descriptor_ui": "D042002", "major_topic": true }, { "descriptor": "Glucose", "descriptor_ui": "D005947", "major_topic": true }, { "descriptor": "Histones", "descriptor_ui": "D006657", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Intra-Abdominal Fat", "descriptor_ui": "D050152", "major_topic": true }, { "descriptor": "Jumonji Domain-Containing Histone Demethylases", "descriptor_ui": "D056484", "major_topic": true }, { "descriptor": "Ketoglutaric Acids", "descriptor_ui": "D007656", "major_topic": true }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Transcription Factors", "descriptor_ui": "D014157", "major_topic": false } ], "publication": { "conference_name": null, "date": "2025 Jul 26", "date_precision": "day", "issue": "8", "normalized_date": "2025-07-26", "pages": "116060", "proceedings_title": null, "publisher": "", "title": "Cell reports", "volume": "44", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Glucose-activated JMJD1A drives visceral adipogenesis via alpha-ketoglutarate-dependent chromatin remodeling.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Multi-cellular organoids are self-assembly aggregates that mimic biological functions and developmental processes of many tissue types in vitro. They are widely employed for disease modeling and functional studies. Hypothalamus-pituitary organoids can be generated through differentiation induction from pluripotent stem cells. However, their maturation is time consuming and labor intensive, and the quality of the resulting organoids can vary. Here, we developed a machine learning model capable of accurately predicting the successful generation of high-quality hypothalamus-pituitary organoids based solely on phase-contrast images captured during the early stage of differentiation. The model achieved an accuracy of 79% using images from organoids on day 9 to predict pituitary cell differentiation at day 40. Moreover, the computational approach identified the shape of the organoid surface as a critical determining factor that significantly affected the prediction. This model can help to enhance the efficiency of organoid induction experiments and illuminate the molecular mechanisms involved in hypothalamus-pituitary differentiation.", "classifications": [ { "id": "JPMJCR2023", "label": "JPMJCR2023", "researcher": "Fumiko Toyoshima", "type": "grant" }, { "id": "Toyoshima", "label": "Group Toyoshima", "parent": "Toyoshima", "type": "group" }, { "id": "Yamamoto", "label": "Group Yamamoto", "parent": "Toyoshima", "type": "group" }, { "id": "Toyoshima", "label": "Team Toyoshima", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Ryusaku", "last_name": "Matsumoto", "name": null }, { "creator_type": "author", "first_name": "Hidetaka", "last_name": "Suga", "name": null }, { "creator_type": "author", "first_name": "Yutaka", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Aoi", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Yamamoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.crmeth.2025.101119" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "40763741" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Hypothalamus", "descriptor_ui": "D007031", "major_topic": true }, { "descriptor": "Machine Learning", "descriptor_ui": "D000069550", "major_topic": true }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Organoids", "descriptor_ui": "D009940", "major_topic": true }, { "descriptor": "Pituitary Gland", "descriptor_ui": "D010902", "major_topic": true } ], "publication": { "conference_name": null, "date": "2025 Jul 26", "date_precision": "day", "issue": "", "normalized_date": "2025-07-26", "pages": "101119", "proceedings_title": null, "publisher": "", "title": "Cell reports methods", "volume": "", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Prediction of the hypothalamus-pituitary organoid formation using machine learning.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "INTRODUCTION: Biomarker status is vital to inform optimal care for individuals with lung cancer, yet implementation of testing has been sub-optimal due to cost, lack of quality and standards, access, awareness, and long turnaround times. Recent therapeutic advances in late-stage and early-stage lung cancer motivated a second global survey on comprehensive biomarker testing in 2024. METHODS: The IASLC convened a global multidisciplinary committee to develop the survey. We used a mixed methods framework, with qualitative focus groups and in-depth interviews informing the primarily quantitative survey. The survey was available in 6 languages. RESULTS: We received 1,677 responses across 90 countries and 14 disciplines. Respondents believe biomarker testing significantly impacts outcomes (98.3%) and have a clear understanding of who should receive testing (91.2%). However, only 63.4% and 29.4% ranked it highly important to perform comprehensive biomarker testing in late- and early-stage, respectively. Many respondents (67%) estimated more than half of individuals with lung cancer are biomarker tested in their country, up from 39% in the 2018 survey (p-value<0.0001). However, 43% of respondents sometimes/often treat patients prior to receiving biomarker results. The highest ranked barriers were cost (27.2%), time (13.9%), sample quality (13.8%), access (12.8%), and awareness (8.0%). We found that healthcare system support for biomarker testing varied by country-level income. CONCLUSIONS: We found improvements in the perception of testing rates compared to 2018 but continued and substantial barriers exist. Future initiatives will use these data to target awareness, access, processes, and policy initiatives to improve comprehensive testing globally.", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Matthew P.", "last_name": "Smeltzer", "name": null }, { "creator_type": "author", "first_name": "Jennifer C.", "last_name": "King", "name": null }, { "creator_type": "author", "first_name": "Casey", "last_name": "Connolly", "name": null }, { "creator_type": "author", "first_name": "Kristin", "last_name": "Brunson", "name": null }, { "creator_type": "author", "first_name": "Maiyan", "last_name": "Chau", "name": null }, { "creator_type": "author", "first_name": "Shuyan", "last_name": "Chen", "name": null }, { "creator_type": "author", "first_name": "Anna", "last_name": "Kerpel-Fronius", "name": null }, { "creator_type": "author", "first_name": "Sylvie", "last_name": "Lantuejoul", "name": null }, { "creator_type": "author", "first_name": "Anant", "last_name": "Mohan", "name": null }, { "creator_type": "author", "first_name": "Allison", "last_name": "Plaxco", "name": null }, { "creator_type": "author", "first_name": "Upal Basu", "last_name": "Roy", "name": null }, { "creator_type": "author", "first_name": "Ricardo", "last_name": "Santos", "name": null }, { "creator_type": "author", "first_name": "Ross", "last_name": "Soo", "name": null }, { "creator_type": "author", "first_name": "Gavitt", "last_name": "Woodard", "name": null }, { "creator_type": "author", "first_name": "Murry W.", "last_name": "Wynes", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null }, { "creator_type": "author", "first_name": "Amanda", "last_name": "Young", "name": null }, { "creator_type": "author", "first_name": "Karen", "last_name": "Kelly", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.jtho.2025.07.114" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "40706709" } }, "mesh": [ { "descriptor": "Attitude of Health Personnel", "descriptor_ui": "D001291", "major_topic": true }, { "descriptor": "Biomarkers, Tumor", "descriptor_ui": "D014408", "major_topic": true }, { "descriptor": "Focus Groups", "descriptor_ui": "D017144", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "International Cooperation", "descriptor_ui": "D007391", "major_topic": false }, { "descriptor": "Interviews as Topic", "descriptor_ui": "D007407", "major_topic": false }, { "descriptor": "Lung Neoplasms", "descriptor_ui": "D008175", "major_topic": true }, { "descriptor": "Neoplasm Staging", "descriptor_ui": "D009367", "major_topic": false }, { "descriptor": "Qualitative Research", "descriptor_ui": "D036301", "major_topic": false }, { "descriptor": "Surveys and Questionnaires", "descriptor_ui": "D011795", "major_topic": false } ], "publication": { "conference_name": null, "date": "2025 Jul 22", "date_precision": "day", "issue": "", "normalized_date": "2025-07-22", "pages": "S1556-0864(25)00937-2", "proceedings_title": null, "publisher": "", "title": "Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer", "volume": "", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "The 2024 International Association for the Study of Lung Cancer (IASLC) Global Survey on Biomarker Testing.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: Macrophages play a pivotal role in both the initiation and resolution of intestinal inflammation, positioning them as potential therapeutic target in inflammatory bowel disease. Intracellular ion such as Ca(2+) are increasingly recognized as key regulators of macrophage function and inflammatory responses. The Na(+)/Ca(2+) exchanger is a membrane protein predominantly expressed in excitable cells, where it regulates intracellular Na(+) and Ca(2+) concentrations. This study aims to elucidate the role of Na(+)/Ca(2+) exchanger in macrophages and its potential implications for inflammatory bowel disease therapy. METHODS: We investigated macrophage function using Na(+)/Ca(2+) exchanger inhibitor and evaluated the effects of Na(+)/Ca(2+) exchanger inhibition in a dextran sodium sulfate-induced mouse model of colitis. RESULTS: Na(+)/Ca(2+) exchanger-1 expression was elevated inflammatory macrophages and colonic tissues from mice with dextran sodium sulfate-induce colitis. Treatment with the Na(+)/Ca(2+) exchanger inhibitor SN-6 ameliorated dextran sodium sulfate-induce colitis symptoms and suppressed the release of pro-inflammatory cytokines from murine and canine macrophage. Inhibition of Na(+)/Ca(2+) exchanger increased Ca(2+) influx and promoted phosphorylated of nuclear factor of activated T-cells in mouse macrophages. Furthermore, Na(+)/Ca(2+) exchanger-1 mRNA expression was upregulated in colonic tissues from both human and canine inflammatory bowel disease patients. CONCLUSIONS: These findings suggest that Na(+)/Ca(2+) exchanger-1 plays a critical role in inflammatory responses in macrophages. Inhibition of Na(+)/Ca(2+) exchanger exerts anti-inflammatory effects and attenuates colonic inflammation across multiple species, including humans and dogs, highlighting its potential as a therapeutic target for inflammatory bowel disease.", "classifications": [ { "id": "Nishida", "label": "Group Nishida", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Kazuhiro", "last_name": "Nishiyama", "name": null }, { "creator_type": "author", "first_name": "Eiichi", "last_name": "Hinoi", "name": null }, { "creator_type": "author", "first_name": "Mitsuru", "last_name": "Kuwamura", "name": null }, { "creator_type": "author", "first_name": "Tomoyo", "last_name": "Nabetani", "name": null }, { "creator_type": "author", "first_name": "Shingo", "last_name": "Hatoya", "name": null }, { "creator_type": "author", "first_name": "Masaru", "last_name": "Furuya", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Tani", "name": null }, { "creator_type": "author", "first_name": "Motohiro", "last_name": "Nishida", "name": null }, { "creator_type": "author", "first_name": "Yasu-Taka", "last_name": "Azuma", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.intimp.2025.115254" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "40700831" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Anti-Inflammatory Agents", "descriptor_ui": "D000893", "major_topic": true }, { "descriptor": "Calcium", "descriptor_ui": "D002118", "major_topic": false }, { "descriptor": "Colitis", "descriptor_ui": "D003092", "major_topic": true }, { "descriptor": "Colon", "descriptor_ui": "D003106", "major_topic": false }, { "descriptor": "Cytokines", "descriptor_ui": "D016207", "major_topic": false }, { "descriptor": "Dextran Sulfate", "descriptor_ui": "D016264", "major_topic": false }, { "descriptor": "Disease Models, Animal", "descriptor_ui": "D004195", "major_topic": false }, { "descriptor": "Dogs", "descriptor_ui": "D004285", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Inflammatory Bowel Diseases", "descriptor_ui": "D015212", "major_topic": false }, { "descriptor": "Macrophage Activation", "descriptor_ui": "D008262", "major_topic": false }, { "descriptor": "Macrophages", "descriptor_ui": "D008264", "major_topic": true }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Sodium-Calcium Exchanger", "descriptor_ui": "D019831", "major_topic": true } ], "publication": { "conference_name": null, "date": "2025 Jul 22", "date_precision": "day", "issue": "", "normalized_date": "2025-07-22", "pages": "115254", "proceedings_title": null, "publisher": "", "title": "International immunopharmacology", "volume": "163", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Pharmacological inhibition of Na(+)/Ca(2+) exchanger alleviates colitis via modulation of macrophage activity in multiple species.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Idiopathic pulmonary fibrosis (IPF) is a fatal interstitial lung disease characterized by progressive fibrosis of lung parenchyma. The histopathology of IPF exhibits temporal and spatial heterogeneity, including immature fibroblastic foci (FF) and densely collagenized fibrosis. FF serve as dynamic niches of profibrotic fibroblasts and play a pivotal role in fibrosis progression and transition into dense fibrosis (DF). Here, we integrated single-cell RNA sequencing (scRNA-seq) with spatial transcriptomics to elucidate cellular heterogeneity and the novel cell type involved not only in FF formation but also in DF development. We identified a novel myofibroblast population, WNT5A+ CTHRC1+ myofibroblasts, enriched in both FF and DF regions, underscoring their pivotal role in fibrosis progression. Differential gene expression analysis revealed the activation of p21-activated kinase 2 (PAK2) in these fibrotic areas, including WNT5A+ CTHRC1+ myofibroblasts. PAK inhibition significantly suppressed TGF-beta-induced myofibroblast differentiation and collagen production in IPF-derived fibroblasts. Furthermore, in a bleomycin-induced lung fibrosis mouse model, intraperitoneal administration of the PAK inhibitor significantly attenuated fibrotic progression. This study highlights the therapeutic potential of PAK inhibition for IPF, particularly targeting pathogenic fibroblasts within both FF and DF regions. By leveraging spatial transcriptomics and scRNA-seq, we provide a comprehensive molecular and cellular atlas of FF and DF in IPF lung tissue, offering new insights into fibrosis progression and therapeutic intervention.", "classifications": [ { "id": "Okamoto", "label": "Group Okamoto", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Naoaki", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Yuta", "last_name": "Hirano", "name": null }, { "creator_type": "author", "first_name": "Shota", "last_name": "Fujimoto", "name": null }, { "creator_type": "author", "first_name": "Sachi", "last_name": "Matsubayashi", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Ishiguro", "name": null }, { "creator_type": "author", "first_name": "Nobumasa", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Yoshihiko", "last_name": "Shimizu", "name": null }, { "creator_type": "author", "first_name": "Noboru", "last_name": "Takayanagi", "name": null }, { "creator_type": "author", "first_name": "Yoshinori", "last_name": "Kawabata", "name": null }, { "creator_type": "author", "first_name": "Yutaro", "last_name": "Mori", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Okamoto", "name": null }, { "creator_type": "author", "first_name": "Shunsuke", "last_name": "Minagawa", "name": null }, { "creator_type": "author", "first_name": "Kazuyoshi", "last_name": "Kuwano", "name": null }, { "creator_type": "author", "first_name": "Jun", "last_name": "Araya", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Yu", "last_name": "Fujita", "name": null } ], "identifiers": { "doi": { "normalized": "10.1183/13993003.00022-2025" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "40675771" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Bleomycin", "descriptor_ui": "D001761", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Disease Models, Animal", "descriptor_ui": "D004195", "major_topic": false }, { "descriptor": "Fibroblasts", "descriptor_ui": "D005347", "major_topic": true }, { "descriptor": "Gene Expression Profiling", "descriptor_ui": "D020869", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Idiopathic Pulmonary Fibrosis", "descriptor_ui": "D054990", "major_topic": true }, { "descriptor": "Lung", "descriptor_ui": "D008168", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Myofibroblasts", "descriptor_ui": "D058628", "major_topic": false }, { "descriptor": "p21-Activated Kinases", "descriptor_ui": "D054462", "major_topic": true }, { "descriptor": "Single-Cell Analysis", "descriptor_ui": "D059010", "major_topic": false }, { "descriptor": "Transcriptome", "descriptor_ui": "D059467", "major_topic": false }, { "descriptor": "Wnt-5a Protein", "descriptor_ui": "D000071818", "major_topic": false } ], "publication": { "conference_name": null, "date": "2025 Jul 17", "date_precision": "day", "issue": "", "normalized_date": "2025-07-17", "pages": "2500022", "proceedings_title": null, "publisher": "", "title": "The European respiratory journal", "volume": "", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Integrated spatial and single-cell transcriptomics reveal PAK kinase as a therapeutic target in fibroblastic foci and dense fibrosis of IPF.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Prenatal exposure to bisphenol A (BPA), a common endocrine disruptor, has been increasingly implicated in neurodevelopmental disorders, including autism spectrum disorder. This study explores the molecular mechanisms by which prenatal BPA exposure affects alternative RNA splicing in the prefrontal cortex and investigates the potential link between alternative RNA splicing and autism-related behaviors in rat offspring. Using RNA sequencing and high-resolution melting real-time PCR, we identified differentially alternative splicing events associated with autism candidate genes. Gene ontology and pathway analyses revealed significant enrichment of differentially alternative splicing genes and neurological pathways relevant to autism. BPA appears to act through autism-related transcription factors, affecting RNA-binding proteins. Altered expressions of these RNA-binding proteins influenced alternative RNA splicing events within key autism-related genes, implicating them in disrupted synaptogenesis. Behavioral analyses of offspring exposed to BPA revealed autism-associated traits, including hyperactivity, anxiety, and aggression, which correlated with the observed sex-specific alternative RNA splicing patterns. These findings suggest that BPA-induced alterations of transcription factors and RNA-binding proteins affect alternative RNA splicing and synaptic development, potentially contributing to autism pathophysiology. This research underscores the role of environmental factors in autism etiology and highlights the importance of awareness and preventive measures against prenatal BPA exposure.", "classifications": [ { "id": "Imai", "label": "Group Imai", "parent": "Enomoto", "type": "group" }, { "id": "Enomoto", "label": "Team Enomoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Pawinee", "last_name": "Panjabud", "name": null }, { "creator_type": "author", "first_name": "Songphon", "last_name": "Kanlayaprasit", "name": null }, { "creator_type": "author", "first_name": "Surangrat", "last_name": "Thongkorn", "name": null }, { "creator_type": "author", "first_name": "Kwanjira", "last_name": "Songsritaya", "name": null }, { "creator_type": "author", "first_name": "Pattanachat", "last_name": "Lertpeerapan", "name": null }, { "creator_type": "author", "first_name": "Kasidit", "last_name": "Kasitipradit", "name": null }, { "creator_type": "author", "first_name": "Thanawin", "last_name": "Jantheang", "name": null }, { "creator_type": "author", "first_name": "Suthathip", "last_name": "Sarobol", "name": null }, { "creator_type": "author", "first_name": "Thanit", "last_name": "Saeliw", "name": null }, { "creator_type": "author", "first_name": "Valerie W.", "last_name": "Hu", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Imai", "name": null }, { "creator_type": "author", "first_name": "Tewarit", "last_name": "Sarachana", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41598-025-09909-9" }, "pmcid": { "normalized": "PMC12271549" }, "pmid": { "normalized": "40676062" } }, "mesh": [ { "descriptor": "Alternative Splicing", "descriptor_ui": "D017398", "major_topic": true }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Autism Spectrum Disorder", "descriptor_ui": "D000067877", "major_topic": false }, { "descriptor": "Autistic Disorder", "descriptor_ui": "D001321", "major_topic": true }, { "descriptor": "Behavior, Animal", "descriptor_ui": "D001522", "major_topic": false }, { "descriptor": "Benzhydryl Compounds", "descriptor_ui": "D001559", "major_topic": true }, { "descriptor": "Bisphenol A Compounds", "descriptor_ui": "D000098826", "major_topic": false }, { "descriptor": "Endocrine Disruptors", "descriptor_ui": "D052244", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Phenols", "descriptor_ui": "D010636", "major_topic": true }, { "descriptor": "Prefrontal Cortex", "descriptor_ui": "D017397", "major_topic": true }, { "descriptor": "Pregnancy", "descriptor_ui": "D011247", "major_topic": false }, { "descriptor": "Prenatal Exposure Delayed Effects", "descriptor_ui": "D011297", "major_topic": true }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Rats, Sprague-Dawley", "descriptor_ui": "D017207", "major_topic": false }, { "descriptor": "RNA Splicing", "descriptor_ui": "D012326", "major_topic": true }, { "descriptor": "RNA-Binding Proteins", "descriptor_ui": "D016601", "major_topic": false } ], "publication": { "conference_name": null, "date": "2025 Jul 17", "date_precision": "day", "issue": "1", "normalized_date": "2025-07-17", "pages": "25996", "proceedings_title": null, "publisher": "", "title": "Scientific reports", "volume": "15", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Prenatal exposure to bisphenol A disrupts RNA splicing in the prefrontal cortex and promotes behaviors related to autism in offspring.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "There is robust evidence that senescence can be propagated in vitro through mechanisms including the senescence-associated secretory phenotype, resulting in the non-cell-autonomous induction of secondary senescence. However, the induction, regulation and physiological role of secondary senescence in vivo remain largely unclear. Here we generated senescence-inducible mouse models expressing either the constitutively active form of MEK1 or MKK6 and mCherry, to map primary and secondary senescent cells. Our models recapitulate characteristic features of senescence and demonstrate that primary and secondary phenotypes are highly tissue- and inducer-dependent. Spatially resolved RNA expression analyses at the single-cell level reveal that each senescence induction results in a unique transcriptional profile-even within cells of the same cell type-explaining the heterogeneity of senescent cells in vivo. Furthermore, we show that interleukin-1beta, primarily derived from macrophages, induces secondary phenotypes. Our findings provide insight into secondary senescence in vivo and useful tools for understanding and manipulating senescence during aging.", "classifications": [ { "id": "JPMJCR2023", "label": "JPMJCR2023", "researcher": "Fumiko Toyoshima", "type": "grant" }, { "id": "Toyoshima", "label": "Group Toyoshima", "parent": "Toyoshima", "type": "group" }, { "id": "Yamamoto", "label": "Group Yamamoto", "parent": "Toyoshima", "type": "group" }, { "id": "Toyoshima", "label": "Team Toyoshima", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yuko", "last_name": "Sogabe", "name": null }, { "creator_type": "author", "first_name": "Hirofumi", "last_name": "Shibata", "name": null }, { "creator_type": "author", "first_name": "Mio", "last_name": "Kabata", "name": null }, { "creator_type": "author", "first_name": "Akito", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Kanae", "last_name": "Mitsunaga", "name": null }, { "creator_type": "author", "first_name": "Kazunori", "last_name": "Sunadome", "name": null }, { "creator_type": "author", "first_name": "May", "last_name": "Nakajima-Koyama", "name": null }, { "creator_type": "author", "first_name": "Michitada", "last_name": "Hirano", "name": null }, { "creator_type": "author", "first_name": "Eisuke", "last_name": "Nishida", "name": null }, { "creator_type": "author", "first_name": "Knut", "last_name": "Woltjen", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Seno", "name": null }, { "creator_type": "author", "first_name": "Yasuhiro", "last_name": "Yamada", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Yamamoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s43587-025-00917-y" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "40646305" } }, "mesh": [ { "descriptor": "Aging", "descriptor_ui": "D000375", "major_topic": true }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cellular Senescence", "descriptor_ui": "D016922", "major_topic": true }, { "descriptor": "Fibroblasts", "descriptor_ui": "D005347", "major_topic": false }, { "descriptor": "Interleukin-1beta", "descriptor_ui": "D053583", "major_topic": false }, { "descriptor": "Macrophages", "descriptor_ui": "D008264", "major_topic": false }, { "descriptor": "MAP Kinase Kinase 1", "descriptor_ui": "D048369", "major_topic": false }, { "descriptor": "MAP Kinase Kinase 6", "descriptor_ui": "D048669", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Transgenic", "descriptor_ui": "D008822", "major_topic": false }, { "descriptor": "Phenotype", "descriptor_ui": "D010641", "major_topic": false }, { "descriptor": "Senescence-Associated Secretory Phenotype", "descriptor_ui": "D000089262", "major_topic": false } ], "publication": { "conference_name": null, "date": "2025 Jul 11", "date_precision": "day", "issue": "", "normalized_date": "2025-07-11", "pages": "", "proceedings_title": null, "publisher": "", "title": "Nature aging", "volume": "", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Characterizing primary and secondary senescence in vivo.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Tyrosine kinase inhibitors (TKIs) are initially efficacious against anaplastic lymphoma kinase (ALK) fusion gene-positive lung adenocarcinoma (ALK+ LUAD), but acquired resistance inevitably occurs. Therefore, alternative treatment strategies are needed for TKI-resistant cases. Although the use of immune checkpoint inhibitors (ICIs) has improved the prognosis of patients with lung cancer, patients with ALK+ LUAD exhibit little or no response to immunotherapy and the underlying resistance mechanisms remain unknown. Here, we explored the immunological status of the tumor microenvironment (TME) in ALK+ LUAD tissues. Tumor-infiltrating leukocyte analysis revealed reduced numbers of effector T cells and increased myeloid-derived suppressor cells (MDSCs) relative to ALK- LUAD cases, indicating that ALK+ LUAD has a myeloid cell-dominant immunosuppressive TME. Single-cell RNA-sequencing analysis identified a subset of macrophages that expressed most T cell-attractant chemokines (CXCL9, CXCL10, and CXCL11), and the macrophages were inactivated in ALK+ LUAD. In contrast, ALK+ LUAD expressed high levels of MDSC-attractant chemokines (CXCL1 and CXCL8). In addition, ALK+ LUAD showed higher levels of IL-6, an MDSC-inducing cytokine, than ALK- LUAD. An IL-6R inhibitor transformed the TME in a murine ALK+ LUAD model, shifting it from an immunosuppressive to a T cell-dominant status. Although ICI monotherapy lacked antitumor effects, a combination of ICI and the IL-6R inhibitor had significant antitumor effects in mice. Our findings illustrate the molecular basis of fusion gene-mediated immunosuppressive TMEs, providing a rationale for a novel combination immunotherapy for ALK+ LUAD.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Kosuke", "last_name": "Arai", "name": null }, { "creator_type": "author", "first_name": "Yukari", "last_name": "Nishito", "name": null }, { "creator_type": "author", "first_name": "Hideaki", "last_name": "Mizuno", "name": null }, { "creator_type": "author", "first_name": "Noriko", "last_name": "Motoi", "name": null }, { "creator_type": "author", "first_name": "Nobuyoshi", "last_name": "Hiraoka", "name": null }, { "creator_type": "author", "first_name": "Masanori", "last_name": "Fuse", "name": null }, { "creator_type": "author", "first_name": "Yasuhito", "last_name": "Arai", "name": null }, { "creator_type": "author", "first_name": "Tatsuhiro", "last_name": "Shibata", "name": null }, { "creator_type": "author", "first_name": "Yukiko", "last_name": "Sonobe", "name": null }, { "creator_type": "author", "first_name": "Yoko", "last_name": "Kayukawa", "name": null }, { "creator_type": "author", "first_name": "Toru", "last_name": "Maruyama", "name": null }, { "creator_type": "author", "first_name": "Hironori", "last_name": "Fukuda", "name": null }, { "creator_type": "author", "first_name": "Yukihiro", "last_name": "Mizoguchi", "name": null }, { "creator_type": "author", "first_name": "Yukiko", "last_name": "Aikawa", "name": null }, { "creator_type": "author", "first_name": "Yukihiro", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Shun-Ichi", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Hiromi", "last_name": "Sakamoto", "name": null }, { "creator_type": "author", "first_name": "Makiko", "last_name": "Yamashita", "name": null }, { "creator_type": "author", "first_name": "Shigehisa", "last_name": "Kitano", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Nagata", "name": null }, { "creator_type": "author", "first_name": "Risa", "last_name": "Mitsumori", "name": null }, { "creator_type": "author", "first_name": "Kouichi", "last_name": "Ozaki", "name": null }, { "creator_type": "author", "first_name": "Shumpei", "last_name": "Niida", "name": null }, { "creator_type": "author", "first_name": "Yae", "last_name": "Kanai", "name": null }, { "creator_type": "author", "first_name": "Akiyoshi", "last_name": "Hirayama", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Teruhiko", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Kazuki", "last_name": "Yasuda", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Ochiai", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Tsunoda", "name": null }, { "creator_type": "author", "first_name": "Kazunori", "last_name": "Aoki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1158/2326-6066.cir-24-0532" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "40627846" } }, "mesh": [ { "descriptor": "Adenocarcinoma of Lung", "descriptor_ui": "D000077192", "major_topic": true }, { "descriptor": "Anaplastic Lymphoma Kinase", "descriptor_ui": "D000077548", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Gene Rearrangement", "descriptor_ui": "D015321", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Lung Neoplasms", "descriptor_ui": "D008175", "major_topic": true }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Myeloid Cells", "descriptor_ui": "D022423", "major_topic": true }, { "descriptor": "Myeloid-Derived Suppressor Cells", "descriptor_ui": "D000072737", "major_topic": true }, { "descriptor": "Oncogene Proteins, Fusion", "descriptor_ui": "D015514", "major_topic": true }, { "descriptor": "Tumor Microenvironment", "descriptor_ui": "D059016", "major_topic": true } ], "publication": { "conference_name": null, "date": "2025 Jul 8", "date_precision": "day", "issue": "", "normalized_date": "2025-07-08", "pages": "", "proceedings_title": null, "publisher": "", "title": "Cancer immunology research", "volume": "", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "EML4-ALK rearrangement creates a distinctive myeloid cell-dominant immunosuppressive microenvironment in lung cancer.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "CONTEXT: Molecular Tumor Boards (MTBs) are multidisciplinary meetings of specialists dedicated to analyzing biomarker test results to provide personalized treatment recommendations. However, global disparities in the successful implementation of MTBs exist, driven by unequal access to molecular diagnostics and supportive multidimensional expertise. OBJECTIVE: To establish recommendations for MTB implementation, outline practical frameworks for their operation, and address disparities in expertise and resources between new and established MTBs. DESIGN: A modified Delphi method involved 37 international experts in three survey rounds and online meetings, with consensus defined as >/=75% agreement. RESULTS: The panel identified a molecular biologist or pathologist with expertise in molecular diagnostics and tumor-specific medical oncologists as indispensable MTB members. Case selection should reflect institutional expertise and volume, with newer MTBs reviewing less selected cases to gain experience. Regular meetings are advised to avoid delays beyond 14 days from result availability to discussion. Reporting should be standardized to include clinicopathologic data (tumor characteristics, treatment history), biomarker findings (testing results, sample details), and recommendations (treatment, retesting, genetic counseling). Treatment options should be ranked by the level of evidence for actionability and may include options not available locally. Performance evaluation should consider changes in patient management based on MTB input and matched therapy rates. CONCLUSIONS: These MTB consensus recommendations are applicable across tumor types, despite being developed by lung cancer and molecular specialists and initiated by the International Association for the Study of Lung Cancer (IASLC). They provide a structured framework for MTB implementation, report standardization, case selection, and quality assessment, aiming to standardize practice and address gaps in expertise for personalized cancer care.", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Mihaela", "last_name": "Aldea", "name": null }, { "creator_type": "author", "first_name": "Julia K.", "last_name": "Rotow", "name": null }, { "creator_type": "author", "first_name": "Maria", "last_name": "Arcila", "name": null }, { "creator_type": "author", "first_name": "Matthew", "last_name": "Hatton", "name": null }, { "creator_type": "author", "first_name": "Lynette", "last_name": "Sholl", "name": null }, { "creator_type": "author", "first_name": "Christian", "last_name": "Rolfo", "name": null }, { "creator_type": "author", "first_name": "Marco", "last_name": "Tagliamento", "name": null }, { "creator_type": "author", "first_name": "Teodora", "last_name": "Radonic", "name": null }, { "creator_type": "author", "first_name": "Kurt A.", "last_name": "Schalper", "name": null }, { "creator_type": "author", "first_name": "Vivek", "last_name": "Subbiah", "name": null }, { "creator_type": "author", "first_name": "Umberto", "last_name": "Malapelle", "name": null }, { "creator_type": "author", "first_name": "Anja C.", "last_name": "Roden", "name": null }, { "creator_type": "author", "first_name": "Rami", "last_name": "Manochakian", "name": null }, { "creator_type": "author", "first_name": "Ming-Sound", "last_name": "Tsao", "name": null }, { "creator_type": "author", "first_name": "Helena", "last_name": "Linardou", "name": null }, { "creator_type": "author", "first_name": "Rina", "last_name": "Hui", "name": null }, { "creator_type": "author", "first_name": "Silvia", "last_name": "Novello", "name": null }, { "creator_type": "author", "first_name": "Alastair", "last_name": "Greystoke", "name": null }, { "creator_type": "author", "first_name": "Anjali", "last_name": "Saqi", "name": null }, { "creator_type": "author", "first_name": "Sylvie", "last_name": "Lantuejoul", "name": null }, { "creator_type": "author", "first_name": "David M.", "last_name": "Hwang", "name": null }, { "creator_type": "author", "first_name": "Kelly", "last_name": "Nevins", "name": null }, { "creator_type": "author", "first_name": "Murry", "last_name": "Wynes", "name": null }, { "creator_type": "author", "first_name": "Saiama", "last_name": "Waqar", "name": null }, { "creator_type": "author", "first_name": "Yuchen", "last_name": "Han", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null }, { "creator_type": "author", "first_name": "Wei-Chin", "last_name": "Chang", "name": null }, { "creator_type": "author", "first_name": "Takuo", "last_name": "Hayashi", "name": null }, { "creator_type": "author", "first_name": "Tae-Jung", "last_name": "Kim", "name": null }, { "creator_type": "author", "first_name": "Paul", "last_name": "Hofman", "name": null }, { "creator_type": "author", "first_name": "Fabio", "last_name": "Tavora", "name": null }, { "creator_type": "author", "first_name": "Fred R.", "last_name": "Hirsch", "name": null }, { "creator_type": "author", "first_name": "Valeria", "last_name": "Denninghoff", "name": null }, { "creator_type": "author", "first_name": "Natasha B.", "last_name": "Leighl", "name": null }, { "creator_type": "author", "first_name": "Alexander", "last_name": "Drilon", "name": null }, { "creator_type": "author", "first_name": "Wendy A.", "last_name": "Cooper", "name": null }, { "creator_type": "author", "first_name": "Sanja", "last_name": "Dacic", "name": null }, { "creator_type": "author", "first_name": "Pranshu", "last_name": "Mohindra", "name": null }, { "creator_type": "author", "first_name": "Nick", "last_name": "Pavlakis", "name": null }, { "creator_type": "author", "first_name": "Fernando", "last_name": "Lopez-Rios", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.jtho.2025.07.009" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "40633839" } }, "mesh": [ { "descriptor": "Biomarkers, Tumor", "descriptor_ui": "D014408", "major_topic": true }, { "descriptor": "Delphi Technique", "descriptor_ui": "D003697", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Lung Neoplasms", "descriptor_ui": "D008175", "major_topic": true } ], "publication": { "conference_name": null, "date": "2025 Jul 7", "date_precision": "day", "issue": "", "normalized_date": "2025-07-07", "pages": "S1556-0864(25)00831-7", "proceedings_title": null, "publisher": "", "title": "Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer", "volume": "", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Molecular Tumor Boards: A consensus statement from the International Association for the Study of Lung Cancer.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Plants generate organs continuously during post-embryonic development. Thus, their ability to preserve stem cells in changing environments is crucial for their survival. Genotoxic stress threatens genome stability in all somatic cells. However, in the meristem, only the stem cells actively die in response to DNA damage, followed by stem cell replenishment that guarantees genome stability in these cells. Cytokinin biosynthesis-induced inhibition of downward auxin flow participates in DNA damage-induced stem cell death in roots. Without this system, stem cell death occurs at a reduced but significant level, suggesting another mechanism governing the DNA damage response in stem cells. Here, we demonstrate that in response to DNA double-strand breaks, the AUXIN/INDOLE-3-ACETIC ACID (Aux/IAA) family members IAA5 and IAA29, encoding negative regulators of auxin signaling, are induced in Arabidopsis (Arabidopsis thaliana) roots. The transcription factor SUPPRESSOR OF GAMMA RESPONSE 1 directly induces their expression as an active response to DNA damage. In the iaa5 iaa29 double mutant, DNA damage-induced stem cell death is greatly suppressed, while it is fully restored by the expression of a stable form of IAA5 in vascular stem cells. Our genetic data reveal that reduced auxin signaling around the stem cell niche, caused by IAA5 and IAA29 induction and enhanced cytokinin biosynthesis, is a prerequisite for cell death induction, thus playing a central role in maintaining genome integrity in root stem cells.", "classifications": [ { "id": "Higaki", "label": "Group Higaki", "parent": "Ueda", "type": "group" }, { "id": "Ueda", "label": "Team Ueda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Naoki", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Nobuo", "last_name": "Ogita", "name": null }, { "creator_type": "author", "first_name": "Toshiya", "last_name": "Koike", "name": null }, { "creator_type": "author", "first_name": "Kohei", "last_name": "Nishimura", "name": null }, { "creator_type": "author", "first_name": "Soichi", "last_name": "Inagaki", "name": null }, { "creator_type": "author", "first_name": "Ye", "last_name": "Zhang", "name": null }, { "creator_type": "author", "first_name": "Takumi", "last_name": "Higaki", "name": null }, { "creator_type": "author", "first_name": "Masaaki", "last_name": "Umeda", "name": null } ], "identifiers": { "doi": { "normalized": "10.1093/plphys/kiaf303" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "40611820" } }, "mesh": [ { "descriptor": "Arabidopsis", "descriptor_ui": "D017360", "major_topic": true }, { "descriptor": "Arabidopsis Proteins", "descriptor_ui": "D029681", "major_topic": true }, { "descriptor": "Cell Death", "descriptor_ui": "D016923", "major_topic": false }, { "descriptor": "Cytokinins", "descriptor_ui": "D003583", "major_topic": false }, { "descriptor": "DNA Damage", "descriptor_ui": "D004249", "major_topic": true }, { "descriptor": "Gene Expression Regulation, Plant", "descriptor_ui": "D018506", "major_topic": false }, { "descriptor": "Indoleacetic Acids", "descriptor_ui": "D007210", "major_topic": false }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": false }, { "descriptor": "Plant Roots", "descriptor_ui": "D018517", "major_topic": true }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Stem Cells", "descriptor_ui": "D013234", "major_topic": true }, { "descriptor": "Transcription Factors", "descriptor_ui": "D014157", "major_topic": true } ], "publication": { "conference_name": null, "date": "2025 Jul 4", "date_precision": "day", "issue": "", "normalized_date": "2025-07-04", "pages": "kiaf303", "proceedings_title": null, "publisher": "", "title": "Plant physiology", "volume": "", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "The transcriptional repressors IAA5 and IAA29 participate in DNA damage-induced stem cell death in Arabidopsis roots.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Maternal behaviors, which are crucial for the survival of mammalian infants, require the coordinated operation of multiple brain regions to process infant cues, make decisions, and execute motor plans. Although these processes likely demand higher cognitive functions, the prefrontal areas that regulate limbic parental programs remains poorly understood. Here, we show that the orbitofrontal cortex (OFC) excitatory projection neurons promote alloparental caregiving behaviors in female mice. By chronic microendoscopy, we observed robust yet adaptable representations of pup-directed anticipatory and motor-related activities within the OFC. Some of these plastic responses were significantly overlapped with those related to nonsocial reward signals. The inactivation of OFC output reduced the phasic activities of midbrain dopamine (DA) neurons specifically tied to pup retrieval and impaired the modulation of DA release to the ventral striatum during the acquisition of alloparental behaviors. These findings suggest that the OFC transiently boosts DA activity during the acquisition phase, thereby facilitating the manifestation of alloparental behaviors.", "classifications": [ { "id": "Miyamichi", "label": "Group Miyamichi", "parent": "Enomoto", "type": "group" }, { "id": "Enomoto", "label": "Team Enomoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Gen-Ichi", "last_name": "Tasaka", "name": null }, { "creator_type": "author", "first_name": "Mitsue", "last_name": "Hagihara", "name": null }, { "creator_type": "author", "first_name": "Satsuki", "last_name": "Irie", "name": null }, { "creator_type": "author", "first_name": "Haruna", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Kengo", "last_name": "Inada", "name": null }, { "creator_type": "author", "first_name": "Kenta", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Shigeki", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Kazuto", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Kazunari", "last_name": "Miyamichi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1126/sciadv.adr4620" }, "pmcid": { "normalized": "PMC12219497" }, "pmid": { "normalized": "40601734" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Behavior, Animal", "descriptor_ui": "D001522", "major_topic": true }, { "descriptor": "Dopamine", "descriptor_ui": "D004298", "major_topic": true }, { "descriptor": "Dopaminergic Neurons", "descriptor_ui": "D059290", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Maternal Behavior", "descriptor_ui": "D008425", "major_topic": true }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Prefrontal Cortex", "descriptor_ui": "D017397", "major_topic": true }, { "descriptor": "Reward", "descriptor_ui": "D012201", "major_topic": false } ], "publication": { "conference_name": null, "date": "2025 Jul 4", "date_precision": "day", "issue": "27", "normalized_date": "2025-07-04", "pages": "eadr4620", "proceedings_title": null, "publisher": "", "title": "Science advances", "volume": "11", "year": 2025 }, "ssbd": { "database": [ "ssbd-database-000402" ], "repository": [ "ssbd-repos-000402" ] }, "title": "Orbitofrontal cortex influences dopamine dynamics associated with alloparental behavioral acquisition in female mice.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Jarushka", "last_name": "Naidoo", "name": null }, { "creator_type": "author", "first_name": "Abesh", "last_name": "Niroula", "name": null }, { "creator_type": "author", "first_name": "Dipesh", "last_name": "Uprety", "name": null }, { "creator_type": "author", "first_name": "Matthew", "last_name": "Smeltzer", "name": null }, { "creator_type": "author", "first_name": "Nicole", "last_name": "Geissen", "name": null }, { "creator_type": "author", "first_name": "Raymond U.", "last_name": "Osarogiagbon", "name": null }, { "creator_type": "author", "first_name": "Mari", "last_name": "Mino-Kenudson", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null }, { "creator_type": "author", "first_name": "Kristin", "last_name": "Higgins", "name": null }, { "creator_type": "author", "first_name": "Aakash", "last_name": "Desai", "name": null }, { "creator_type": "author", "first_name": "Karen L.", "last_name": "Reckamp", "name": null }, { "creator_type": "author", "first_name": "Jessica Jiyeong", "last_name": "Lin", "name": null }, { "creator_type": "author", "first_name": "Stephen V.", "last_name": "Liu", "name": null }, { "creator_type": "author", "first_name": "Fiona", "last_name": "Hegi-Johnson Franzcr", "name": null }, { "creator_type": "author", "first_name": "Nagashree", "last_name": "Seetharamu", "name": null }, { "creator_type": "author", "first_name": "David", "last_name": "Harpole", "name": null }, { "creator_type": "author", "first_name": "Martin J.", "last_name": "Edelman", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.jtho.2025.06.028" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "40617395" } }, "mesh": [ { "descriptor": "Carcinoma, Non-Small-Cell Lung", "descriptor_ui": "D002289", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Lung Neoplasms", "descriptor_ui": "D008175", "major_topic": true } ], "publication": { "conference_name": null, "date": "2025 Jul 3", "date_precision": "day", "issue": "", "normalized_date": "2025-07-03", "pages": "S1556-0864(25)00819-6", "proceedings_title": null, "publisher": "", "title": "Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer", "volume": "", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "50 years of Progress in Non-Small Cell Lung Cancer: A New Fellow's Guide in the Clinic.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Although spermatogonial stem cells (SSCs) are considered to rely on glycolysis, they also require specific amino acids for self-renewal. Here we demonstrate a unique role of alanine in sustaining SSCs in vitro through pyruvate generation. Analysis of amino acid requirements in cultured SSCs revealed that alanine is indispensable for SSCs, even in the presence of glucose. Alanine deficiency induced Trp53-dependent apoptosis without affecting the fate commitment of SSCs. Ethanolamine rescued defective proliferation and increased pyruvate formation in alanine-deficient medium. Furthermore, alanine deficiency depleted pyruvate in cultured SSCs, indicating the necessity of alanine-to-pyruvate conversion for self-renewal. While lactate was dispensable, pyruvate maintained long-term SSC cultures through enhanced uridine metabolism. Offspring were born by microinsemination using sperm that developed from cultured SSCs sustained by supra-molar pyruvate. These results show the critical role of alanine in maintaining SSC bioenergetic balance via pyruvate production in vitro.", "classifications": [ { "id": "Yamamoto", "label": "Group Yamamoto", "parent": "Toyoshima", "type": "group" }, { "id": "Toyoshima", "label": "Team Toyoshima", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Takehiro", "last_name": "Miyazaki", "name": null }, { "creator_type": "author", "first_name": "Narumi", "last_name": "Ogonuki", "name": null }, { "creator_type": "author", "first_name": "Mito", "last_name": "Kanatsu-Shinohara", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Shogo", "last_name": "Matoba", "name": null }, { "creator_type": "author", "first_name": "Atsuo", "last_name": "Ogura", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Shinohara", "name": null } ], "identifiers": { "doi": { "normalized": "10.1093/biolre/ioaf144" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "40600665" } }, "mesh": [ { "descriptor": "Adult Germline Stem Cells", "descriptor_ui": "D000072956", "major_topic": true }, { "descriptor": "Alanine", "descriptor_ui": "D000409", "major_topic": true }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Energy Metabolism", "descriptor_ui": "D004734", "major_topic": true }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Pyruvic Acid", "descriptor_ui": "D019289", "major_topic": false }, { "descriptor": "Spermatogonia", "descriptor_ui": "D013093", "major_topic": true }, { "descriptor": "Stem Cells", "descriptor_ui": "D013234", "major_topic": true } ], "publication": { "conference_name": null, "date": "2025 Jul 2", "date_precision": "day", "issue": "", "normalized_date": "2025-07-02", "pages": "ioaf144", "proceedings_title": null, "publisher": "", "title": "Biology of reproduction", "volume": "", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Control of bioenergetic balance in mouse spermatogonial stem cells by alanine metabolism.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Stem wounding is one of the most common abiotic stresses affecting plant development and productivity. During tissue-repair process of partially incised flowering stems of Arabidopsis thaliana, wounded tissues heal by a cascade of processes including tissue adhesion, cell dedifferentiation, cell proliferation, and subsequently tissue redifferentiation leading to the formation of new differentiated tissue. Cell proliferation is a key process in the recovery of wounded tissues. Nonetheless, the mechanisms regulating the initiation of cell proliferation remain elusive. In this study, we identified that jacalin, a lectin derived from the seeds of jackfruits (Artocarpus integrifolia), plays a role in inducing cell proliferation. Adding jacalin on the incision gap of the incised stem caused enhanced cell proliferation. One of A. thaliana JACALIN-RELATED LECTINS, JAL34, was highly expressed especially at 1 to 5 days after incision (DAI). Histological analysis of the defected mutant of jal34 showed an inactive cell proliferation. Our results suggest that JAL34 is involved in initiating cell proliferation during tissue-repair process.", "classifications": [ { "id": "Higaki", "label": "Group Higaki", "parent": "Ueda", "type": "group" }, { "id": "Ueda", "label": "Team Ueda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Afiifah", "last_name": "Machfuudzoh", "name": null }, { "creator_type": "author", "first_name": "Ryo", "last_name": "Koshiba", "name": null }, { "creator_type": "author", "first_name": "Takumi", "last_name": "Higaki", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Ohba", "name": null }, { "creator_type": "author", "first_name": "Masashi", "last_name": "Asahina", "name": null }, { "creator_type": "author", "first_name": "Shinobu", "last_name": "Satoh", "name": null }, { "creator_type": "author", "first_name": "Hiroaki", "last_name": "Iwai", "name": null } ], "identifiers": { "doi": { "normalized": "10.1093/pcp/pcaf071" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "40590500" } }, "mesh": [ { "descriptor": "Arabidopsis", "descriptor_ui": "D017360", "major_topic": true }, { "descriptor": "Arabidopsis Proteins", "descriptor_ui": "D029681", "major_topic": false }, { "descriptor": "Cell Proliferation", "descriptor_ui": "D049109", "major_topic": false }, { "descriptor": "Flowers", "descriptor_ui": "D035264", "major_topic": false }, { "descriptor": "Gene Expression Regulation, Plant", "descriptor_ui": "D018506", "major_topic": false }, { "descriptor": "Plant Lectins", "descriptor_ui": "D037121", "major_topic": true }, { "descriptor": "Plant Stems", "descriptor_ui": "D018547", "major_topic": true } ], "publication": { "conference_name": null, "date": "2025 Jul 1", "date_precision": "day", "issue": "", "normalized_date": "2025-07-01", "pages": "pcaf071", "proceedings_title": null, "publisher": "", "title": "Plant & cell physiology", "volume": "", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Jacalin-Induced Cell Proliferation During Tissue-Repair Process in Partially Incised Flowering Stems of Arabidopsis thaliana.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Follicular lymphoma (FL) is characterized by the expansion of neoplastic follicle structures and is suggested to have a distinctive form of T cell immunity. However, the heterogeneity and role of follicular T cells beyond T follicular helper (T(FH)) cells remain largely unexplored in FL. Here, we performed multi-omics analyses of follicular T cells in FL leveraging pan-cancer single-cell mapping, spatially resolved single-cell transcriptomics and multiplex protein profiling, and functional characterization. We identified transcriptionally and spatially distinct non-T(FH) follicular T cell subsets that expand in FL. These subsets exhibit enhanced anti-tumorigenic properties and form unique spatial niches. Their phenotypes were replicated under interleukin-21-predominant conditions, revealing discrete self-regulatory cellular ecosystems that generate these subsets and may underlie FL clinical behaviors. Furthermore, these subsets robustly stratify FL prognoses, independently of existing prognostic markers. Our findings highlight previously unrecognized immunity that could advance our understanding of lymphoma and improve patient management.", "classifications": [ { "id": "Nishikii", "label": "Group Nishikii", "parent": "Shintaku", "type": "group" }, { "id": "Shintaku", "label": "Team Shintaku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yoshiaki", "last_name": "Abe", "name": null }, { "creator_type": "author", "first_name": "Junko", "last_name": "Zenkoh", "name": null }, { "creator_type": "author", "first_name": "Akinori", "last_name": "Kanai", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Ikeda", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Kaji", "name": null }, { "creator_type": "author", "first_name": "Aya", "last_name": "Sawa", "name": null }, { "creator_type": "author", "first_name": "Ryota", "last_name": "Matsuoka", "name": null }, { "creator_type": "author", "first_name": "Kei", "last_name": "Asayama", "name": null }, { "creator_type": "author", "first_name": "Rikako", "last_name": "Tabata", "name": null }, { "creator_type": "author", "first_name": "Ryota", "last_name": "Ishii", "name": null }, { "creator_type": "author", "first_name": "Manabu", "last_name": "Fujisawa", "name": null }, { "creator_type": "author", "first_name": "Kenichi", "last_name": "Makishima", "name": null }, { "creator_type": "author", "first_name": "Sakurako", "last_name": "Suma", "name": null }, { "creator_type": "author", "first_name": "Yasuhito", "last_name": "Suehara", "name": null }, { "creator_type": "author", "first_name": "Keiichiro", "last_name": "Hattori", "name": null }, { "creator_type": "author", "first_name": "Tatsuhiro", "last_name": "Sakamoto", "name": null }, { "creator_type": "author", "first_name": "Hidekazu", "last_name": "Nishikii", "name": null }, { "creator_type": "author", "first_name": "Chikashi", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Hiroko", "last_name": "Bando", "name": null }, { "creator_type": "author", "first_name": "Ayako", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Yasunori", "last_name": "Ota", "name": null }, { "creator_type": "author", "first_name": "Yoshihito", "last_name": "Otsuka", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Matsubara", "name": null }, { "creator_type": "author", "first_name": "Kosei", "last_name": "Matsue", "name": null }, { "creator_type": "author", "first_name": "Shigeru", "last_name": "Chiba", "name": null }, { "creator_type": "author", "first_name": "Christian", "last_name": "Steidl", "name": null }, { "creator_type": "author", "first_name": "Yutaka", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Mamiko", "last_name": "Sakata-Yanagimoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.ccell.2025.06.013" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "40614737" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Disease Progression", "descriptor_ui": "D018450", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Interleukin-21", "descriptor_ui": "D000098546", "major_topic": false }, { "descriptor": "Interleukins", "descriptor_ui": "D007378", "major_topic": false }, { "descriptor": "Lymphoma, Follicular", "descriptor_ui": "D008224", "major_topic": true }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Prognosis", "descriptor_ui": "D011379", "major_topic": false }, { "descriptor": "Single-Cell Analysis", "descriptor_ui": "D059010", "major_topic": false }, { "descriptor": "T Follicular Helper Cells", "descriptor_ui": "D000084522", "major_topic": false }, { "descriptor": "T-Lymphocyte Subsets", "descriptor_ui": "D016176", "major_topic": true }, { "descriptor": "Transcriptome", "descriptor_ui": "D059467", "major_topic": false }, { "descriptor": "Tumor Microenvironment", "descriptor_ui": "D059016", "major_topic": false } ], "publication": { "conference_name": null, "date": "2025 Jul 1", "date_precision": "day", "issue": "", "normalized_date": "2025-07-01", "pages": "S1535-6108(25)00263-6", "proceedings_title": null, "publisher": "", "title": "Cancer cell", "volume": "", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Distinct follicular T cell subsets regulate lymphoma progression and outcomes.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Barth syndrome (BTHS) is a rare disease caused by mutations in the tafazzin gene that affects the heart and muscles; however, to date, no clinically effective drugs are available. In BTHS, mitochondrial function is reduced owing to changes in cardiolipin metabolism. We developed mitochonic acid 5 (MA-5), a small-molecule compound that increases ATP levels, improves mitochondrial dynamics, and is effective in treating mitochondrial and muscle diseases. Therefore, this study examined the effectiveness of MA-5 in treating BTHS. The mitochondrial functions of four isolated BTHS skin fibroblasts were examined. Human BTHS induced pluripotent stem cell (iPSC) were differentiated into myoblasts and cardiolipin metabolism and mitochondrial functions were analyzed. RNA-seq was performed to clarify the metabolic changes. Using a Drosophila melanogaster model of BTHS, the effects of MA-5 on motor performance and cardiac phenotype were examined. MA-5 improved mitochondrial function and reduced cell death due to oxidative stress in skin fibroblasts of patients with BTHS. MA-5 promoted ATP production and reduced oxidative stress in human BTHS iPS cell-derived myoblasts. RNA-seq analysis revealed that MA-5 alleviated endoplasmic reticulum stress in BTHS cells. Administration of MA-5 to BTHS Drosophila improved locomotor ability and tachycardia observed in patients with BTHS. Protein interaction analyses suggested colocalization of ATPase and the MA-5-binding protein mitofilin. These data suggested that MA-5 improves BTHS dysfunction and may serve as a novel therapeutic agent for BTHS.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yoshiyasu", "last_name": "Tongu", "name": null }, { "creator_type": "author", "first_name": "Tomoko", "last_name": "Kasahara", "name": null }, { "creator_type": "author", "first_name": "Tetsuro", "last_name": "Matsuhashi", "name": null }, { "creator_type": "author", "first_name": "Yoshitsugu", "last_name": "Oikawa", "name": null }, { "creator_type": "author", "first_name": "Ryota", "last_name": "Akimoto", "name": null }, { "creator_type": "author", "first_name": "Yuhan", "last_name": "Luo", "name": null }, { "creator_type": "author", "first_name": "Sayaka", "last_name": "Sekine", "name": null }, { "creator_type": "author", "first_name": "Momoka", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Hitomi", "last_name": "Kashiwagi", "name": null }, { "creator_type": "author", "first_name": "Shinichiro", "last_name": "Kanno", "name": null }, { "creator_type": "author", "first_name": "Yoshikazu", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Kyohei", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Okubo", "name": null }, { "creator_type": "author", "first_name": "Akihiko", "last_name": "Muto", "name": null }, { "creator_type": "author", "first_name": "Hidetaka", "last_name": "Tokuno", "name": null }, { "creator_type": "author", "first_name": "Chitose", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Chiharu", "last_name": "Kawabe", "name": null }, { "creator_type": "author", "first_name": "Takamasa", "last_name": "Ishikawa", "name": null }, { "creator_type": "author", "first_name": "Shun", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Koichi", "last_name": "Kikuchi", "name": null }, { "creator_type": "author", "first_name": "Shun", "last_name": "Itai", "name": null }, { "creator_type": "author", "first_name": "Takeya", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Takehiro", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Kazuhiro", "last_name": "Igarashi", "name": null }, { "creator_type": "author", "first_name": "Shinji", "last_name": "Fukuda", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Kei", "last_name": "Murayama", "name": null }, { "creator_type": "author", "first_name": "Erina", "last_name": "Kuranaga", "name": null }, { "creator_type": "author", "first_name": "Takafumi", "last_name": "Toyohara", "name": null }, { "creator_type": "author", "first_name": "Takaaki", "last_name": "Abe", "name": null } ], "identifiers": { "doi": { "normalized": "10.1096/fj.202401856rrr" }, "pmcid": { "normalized": "PMC12181814" }, "pmid": { "normalized": "40542649" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Barth Syndrome", "descriptor_ui": "D056889", "major_topic": true }, { "descriptor": "Disease Models, Animal", "descriptor_ui": "D004195", "major_topic": false }, { "descriptor": "Drosophila melanogaster", "descriptor_ui": "D004331", "major_topic": false }, { "descriptor": "Endoplasmic Reticulum Stress", "descriptor_ui": "D059865", "major_topic": false }, { "descriptor": "Fibroblasts", "descriptor_ui": "D005347", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Induced Pluripotent Stem Cells", "descriptor_ui": "D057026", "major_topic": true }, { "descriptor": "Mitochondria", "descriptor_ui": "D008928", "major_topic": true }, { "descriptor": "Muscular Diseases", "descriptor_ui": "D009135", "major_topic": true }, { "descriptor": "Myoblasts", "descriptor_ui": "D032446", "major_topic": false }, { "descriptor": "Oxidative Stress", "descriptor_ui": "D018384", "major_topic": false } ], "publication": { "conference_name": null, "date": "2025 Jun 30", "date_precision": "day", "issue": "12", "normalized_date": "2025-06-30", "pages": "e70739", "proceedings_title": null, "publisher": "", "title": "FASEB journal : official publication of the Federation of American Societies for Experimental Biology", "volume": "39", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Mitochondria-Homing Drug Mitochonic Acid 5 Improves Barth Syndrome Myopathy in a Human-Induced Pluripotent Stem Cell Model and Barth Syndrome Drosophila Model.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Hyphae are filamentous structures that are crucial for the lifestyle of many fungi, allowing rapid colonization of diverse substrates such as dead organic material or living host tissue. One of the key features of fungal hyphae is their remarkable morphogenetic plasticity. During host colonization, phytopathogenic fungi must traverse extremely narrow spaces between plant cells such as the apoplastic space or the plasmodesmata. The mechanisms underlying hyphal plasticity during growth into microspaces are poorly understood. Here, we tested a set of isogenic mutants of Fusarium oxysporum, an important plant pathogen that causes devastating vascular wilt diseases on more than a hundred crops, for their ability to cross extremely narrow 1 microm channels, approximately one-quarter the width of hyphae. We found that the conserved Mpk1 cell wall integrity mitogen-activated protein kinase (MAPK) cascade is required for efficient growth of hyphae through the microchannels, whereas the two other MAPK pathways, the Fmk1 invasive growth and the Hog1 hyperosmolarity response cascades, are dispensable for this process. Staining with specific probes showed a reduction in both chitin and glucan content in the cell wall of hyphae growing within the 1 microm channel. We further establish that channel passage in cell wall remodeling mutants is impaired due to their inability to constrict hyphal diameter, and this defect can be rescued by increasing extracellular osmolarity. Both the cell wall integrity mutants impaired in microchannel passage, as well as the invasive growth mutants unable to penetrate cellophane membranes, caused significantly reduced mortality in tomato plants. Our study reveals that two morphogenetic processes essential for plant infection, which are governed by distinct cellular pathways, contribute independently to fungal phytopathogenicity.IMPORTANCEThis study highlights the critical role of hyphal plasticity and cell wall remodeling in the pathogenicity of Fusarium oxysporum, a major plant pathogen affecting over a hundred crops. The ability of fungal hyphae to traverse narrow plant tissue spaces, such as apoplastic gaps and plasmodesmata, is essential for successful host colonization. The research demonstrates that the Mpk1 mitogen-activated protein kinase (MAPK) pathway, responsible for cell wall integrity, is crucial for hyphal growth through microspaces, while other MAPK pathways are not. Staining with specific probes showed a reduction in both chitin and glucan content in the cell wall of hyphae growing within 1 microm width channels. Both the cell wall integrity mutants impaired in microchannel passage, as well as the invasive growth mutants unable to penetrate cellophane membranes, caused significantly reduced mortality in tomato plants. Our study reveals that two morphogenetic processes essential for plant infection, which are governed by distinct cellular pathways, contribute independently to fungal phytopathogenicity.", "classifications": [ { "id": "Sato", "label": "Group Sato", "parent": "Tsuchiya", "type": "group" }, { "id": "Tsuchiya", "label": "Team Tsuchiya", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Hinata", "last_name": "Miki", "name": null }, { "creator_type": "author", "first_name": "Melani Mariscal", "last_name": "Gomez", "name": null }, { "creator_type": "author", "first_name": "Ayaka", "last_name": "Itani", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Yamanaka", "name": null }, { "creator_type": "author", "first_name": "Yoshikatsu", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Antonio", "last_name": "Di Pietro", "name": null }, { "creator_type": "author", "first_name": "Norio", "last_name": "Takeshita", "name": null } ], "identifiers": { "doi": { "normalized": "10.1128/mbio.01184-25" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "40586248" } }, "mesh": [ { "descriptor": "Cell Wall", "descriptor_ui": "D002473", "major_topic": true }, { "descriptor": "Chitin", "descriptor_ui": "D002686", "major_topic": false }, { "descriptor": "Fungal Proteins", "descriptor_ui": "D005656", "major_topic": false }, { "descriptor": "Fusarium", "descriptor_ui": "D005670", "major_topic": true }, { "descriptor": "Glucans", "descriptor_ui": "D005936", "major_topic": false }, { "descriptor": "Hyphae", "descriptor_ui": "D025301", "major_topic": true }, { "descriptor": "Mitogen-Activated Protein Kinases", "descriptor_ui": "D020928", "major_topic": false }, { "descriptor": "Plant Diseases", "descriptor_ui": "D010935", "major_topic": false }, { "descriptor": "Solanum lycopersicum", "descriptor_ui": "D018551", "major_topic": false } ], "publication": { "conference_name": null, "date": "2025 Jun 30", "date_precision": "day", "issue": "", "normalized_date": "2025-06-30", "pages": "e0118425", "proceedings_title": null, "publisher": "", "title": "mBio", "volume": "", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Cell wall remodeling in a fungal pathogen is required for hyphal growth into microspaces.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "", "classifications": [ { "id": "Onami", "label": "Group Onami", "parent": "Fujiwara", "type": "group" }, { "id": "Fujiwara", "label": "Team Fujiwara", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Hirabayashi", "last_name": "Yusuke", "name": null }, { "creator_type": "author", "first_name": "Onami", "last_name": "Shuichi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1093/jmicro/dfaf026" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "40576096" } }, "mesh": [], "publication": { "conference_name": null, "date": "2025 Jun 26", "date_precision": "day", "issue": "3", "normalized_date": "2025-06-26", "pages": "145", "proceedings_title": null, "publisher": "", "title": "Microscopy (Oxford, England)", "volume": "74", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Bioimaging and image analysis at scale.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Nitrous oxide (N2O) is a potent greenhouse gas and an ozone-depleting substance. Electrocatalytic N2O reduction (e-N2ORR) is a promising approach to remove N2O from the air under ambient conditions. However, developing noble-metal-free e-N2ORR electrocatalysts with high Faradaic efficiency (FE) and turnover frequency (TOF) remains a challenge because of the weak binding of N2O and the high kinetic barrier for deoxygenation reaction. In this work, inspired by the multinuclear copper active site of nitrous oxide reductases, a binuclear copper complex of 3,5-diamino-1,2,4-triazole supported on carbon black of Ketjenblack (CuHdatrz/KB) was utilized for the e-N2ORR at pH 13 and 298 K. CuHdatrz/KB achieves a high FE of approximately 100% at -0.3 V vs. RHE for the e-N2ORR to N2 and TOF up to approximately 700 h-1, which is one-two orders of magnitude higher than those of the previously reported molecular-based catalysts. In situ X-ray absorption spectroscopy confirmed that Cu(II) ions of CuHdatrz/KB are reduced to Cu(I) keeping the binuclear core, suggesting that the multinuclear copper active sites is crucial to efficiently catalyze the e-N2ORR like the nitrous oxide reductase.", "classifications": [ { "id": "Hijikata", "label": "Group Hijikata", "parent": "Tsuchiya", "type": "group" }, { "id": "Tsuchiya", "label": "Team Tsuchiya", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Zhengwei", "last_name": "Ma", "name": null }, { "creator_type": "author", "first_name": "Masaru", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Jenny", "last_name": "Pirillo", "name": null }, { "creator_type": "author", "first_name": "Yuh", "last_name": "Hijikata", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Yohei", "last_name": "Uemura", "name": null }, { "creator_type": "author", "first_name": "Bang", "last_name": "Lu", "name": null }, { "creator_type": "author", "first_name": "Satoru", "last_name": "Takakusagi", "name": null }, { "creator_type": "author", "first_name": "Ken'ichi", "last_name": "Kimijima", "name": null }, { "creator_type": "author", "first_name": "Hideo", "last_name": "Notsu", "name": null }, { "creator_type": "author", "first_name": "Ichizo", "last_name": "Yagi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/anie.202506067" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "40555688" } }, "mesh": [], "publication": { "conference_name": null, "date": "2025 Jun 24", "date_precision": "day", "issue": "", "normalized_date": "2025-06-24", "pages": "e202506067", "proceedings_title": null, "publisher": "", "title": "Angewandte Chemie (International ed. in English)", "volume": "", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "High Turnover Frequency in the Electrocatalytic Reduction of Nitrous Oxide to Dinitrogen at a Binuclear Copper Complex of 3,5-Diamino-1,2,4-Triazole.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Cytological diagnosis of follicular thyroid carcinoma (FTC) is one of the main challenges in the field of endocrine oncology due to the absence of evident morphological indicators. Morphological abnormalities in the nucleus are typically key indicators of cancer cytopathology and are attributed to a range of biochemical alterations in nuclear components. Consequently, Raman spectroscopy has been widely used to detect cancer in various cytological samples, often identifying biochemical changes prior to observable morphological alterations. However, in the case of FTC, cytoplasmic features, such as carotenoids, cytochromes, and lipid droplets, have shown greater diagnostic relevance compared to nuclear features. This study leverages single-cell Raman imaging to explore the spatial origin of diagnostic signals in FTC and normal thyroid (NT) cells, assessing the contributions of the nucleus and cytoplasm independently. Our results demonstrate that Raman spectra from the cytoplasmic region can distinguish between FTC and NT cells with an accuracy of 84% under coculture conditions, consistently across two cell lines originated from two donors and maintaining robustness across multiple devices. In contrast, classification based on nuclear spectra achieved only 53% accuracy, suggesting that biochemical alterations in the cytoplasm play a more significant role in FTC detection than those in the nucleus. Our work elevates the promise of Raman-based cytopathology by providing complementary organelle-dependent information to traditional diagnostic methods and demonstrating transferability across different devices.", "classifications": [ { "id": "Fujita", "label": "Group Fujita", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Aurelien", "last_name": "Pelissier", "name": null }, { "creator_type": "author", "first_name": "Kosuke", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Kentaro", "last_name": "Mochizuki", "name": null }, { "creator_type": "author", "first_name": "J. Nicholas", "last_name": "Taylor", "name": null }, { "creator_type": "author", "first_name": "Jean-Emmanuel", "last_name": "Clement", "name": null }, { "creator_type": "author", "first_name": "Yasuaki", "last_name": "Kumamoto", "name": null }, { "creator_type": "author", "first_name": "Katsumasa", "last_name": "Fujita", "name": null }, { "creator_type": "author", "first_name": "Yoshinori", "last_name": "Harada", "name": null }, { "creator_type": "author", "first_name": "Tamiki", "last_name": "Komatsuzaki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/acs.analchem.4c06544" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "40536131" } }, "mesh": [ { "descriptor": "Adenocarcinoma, Follicular", "descriptor_ui": "D018263", "major_topic": true }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Cell Nucleus", "descriptor_ui": "D002467", "major_topic": true }, { "descriptor": "Cytoplasm", "descriptor_ui": "D003593", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Single-Cell Analysis", "descriptor_ui": "D059010", "major_topic": true }, { "descriptor": "Spectrum Analysis, Raman", "descriptor_ui": "D013059", "major_topic": true }, { "descriptor": "Thyroid Neoplasms", "descriptor_ui": "D013964", "major_topic": true } ], "publication": { "conference_name": null, "date": "2025 Jun 19", "date_precision": "day", "issue": "", "normalized_date": "2025-06-19", "pages": "", "proceedings_title": null, "publisher": "", "title": "Analytical chemistry", "volume": "", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Beyond the Nucleus: Cytoplasmic Dominance in Follicular Thyroid Carcinoma Detection Using Single-Cell Raman Imaging across Multiple Devices.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: Virotherapy eradicates tumors by directly killing cancer cells and causing adjuvant effects. However, the mechanism by which non-replicating virotherapy exerts anti-tumor effects is unclear. METHODS: In this study, we investigated the genes that mediate the anti-tumor effects of ultraviolet (UV)-irradiated Hemagglutinating Virus of Japan envelope (HVJ-E) using RNA sequencing, gene knockout, and a drug-inducible gene expression system. We examined the antitumor effects of Apolipoprotein d (Apod) using genome-wide CRISPR library screening, in situ biotinylation combined with mass spectrometry, flow cytometry, biochemistry, and tumor-bearing mouse models. RESULTS: Here, we show that HVJ-E represses tumor growth via Irf7-induced Apod expression in tumor cells in vivo. Irf7 in B16F10 cells is a pivotal transcription factor for HVJ-E-induced anti-tumor effects. Apod substantially suppresses tumor growth even in HVJ-E-insensitive tumors. Apod is required to increase NKG2D-ligand genes in HVJ-E-treated tumors. Genome-wide CRISPR library screening and in situ biotinylation of Apod reveal an association of Apod with ERK2. Mechanistically, Apod prevents the nuclear translocation of ERK2 and Importin7, increasing NKG2D-ligands expression in B16F10 cells and attenuating tumor growth. Treating a local tumor with a combination therapy of Apod with the anti-OX40, T cell costimulatory molecule, antibody substantially repressed tumor growth in target and non-target lesions alongside T cell activation. CONCLUSION: Our findings provide insights into the molecular mechanisms of how HVJ-E induces anti-tumor effects and can aid the development of therapeutic strategies for eliciting anti-tumor immunity.", "classifications": [ { "id": "Yusa", "label": "Group Yusa", "parent": "Eiraku", "type": "group" }, { "id": "Eiraku", "label": "Team Eiraku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Airi", "last_name": "Ishibashi", "name": null }, { "creator_type": "author", "first_name": "Noriko", "last_name": "Ohta", "name": null }, { "creator_type": "author", "first_name": "Yuko", "last_name": "Uegaki", "name": null }, { "creator_type": "author", "first_name": "Hidefumi", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Katsuya", "last_name": "Fukino", "name": null }, { "creator_type": "author", "first_name": "Yuuta", "last_name": "Hisatomi", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Tanemura", "name": null }, { "creator_type": "author", "first_name": "Riuko", "last_name": "Ohashi", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Kitamura", "name": null }, { "creator_type": "author", "first_name": "Kotaro", "last_name": "Saga", "name": null }, { "creator_type": "author", "first_name": "Yasuhide", "last_name": "Yoshimura", "name": null }, { "creator_type": "author", "first_name": "Satoko", "last_name": "Inubushi", "name": null }, { "creator_type": "author", "first_name": "Kyoso", "last_name": "Ishida", "name": null }, { "creator_type": "author", "first_name": "Yoko", "last_name": "Ino", "name": null }, { "creator_type": "author", "first_name": "Yayoi", "last_name": "Kimura", "name": null }, { "creator_type": "author", "first_name": "Kenjiro", "last_name": "Sawada", "name": null }, { "creator_type": "author", "first_name": "Tadashi", "last_name": "Kimura", "name": null }, { "creator_type": "author", "first_name": "Eiji", "last_name": "Kiyohara", "name": null }, { "creator_type": "author", "first_name": "Kosuke", "last_name": "Yusa", "name": null }, { "creator_type": "author", "first_name": "Hidehisa", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Yasufumi", "last_name": "Kaneda", "name": null }, { "creator_type": "author", "first_name": "Keisuke", "last_name": "Nimura", "name": null } ], "identifiers": { "doi": { "normalized": "10.1136/jitc-2024-011442" }, "pmcid": { "normalized": "PMC12182123" }, "pmid": { "normalized": "40541272" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Apolipoproteins D", "descriptor_ui": "D053399", "major_topic": true }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Oncolytic Virotherapy", "descriptor_ui": "D050130", "major_topic": true } ], "publication": { "conference_name": null, "date": "2025 Jun 19", "date_precision": "day", "issue": "6", "normalized_date": "2025-06-19", "pages": "", "proceedings_title": null, "publisher": "", "title": "Journal for immunotherapy of cancer", "volume": "13", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "HVJ-E links Apolipoprotein d to antitumor effects.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Plant reproduction involves dynamic spatiotemporal changes that occur deep within maternal tissues. In ovules of Arabidopsis thaliana (A. thaliana), one of the two synergid cells degenerates at fertilization, while the fertilized egg cell (zygote) undergoes directional elongation followed by asymmetric division to initiate embryonic patterning. However, morphological analysis of these events has been hampered by the limitations of conventional cell wall staining, which fails to label cells lacking complete walls, and by the requirement for transgenic fluorescent reporters to visualize cell outlines. Here, we report that the membrane-specific fluorescent dye FM4-64 readily permeates ovules, allowing clear visualization of reproductive cell morphology both before and after fertilization. This staining method supports high-resolution time-lapse imaging and quantitative analysis of early embryogenesis in living tissues. Importantly, it is applicable not only to the angiosperm A. thaliana but also to the liverwort Marchantia polymorpha (M. polymorpha) and the fern Ceratopteris richardii (C. richardii), enabling the visualization of live reproductive cell structures within maternal tissues and revealing fertilization-associated morphological changes. This simple and robust method thus provides a valuable tool for spatiotemporal and quantitative analyses of reproductive processes across a broad range of plant species, without the need to generate transgenic lines.", "classifications": [], "creators": [ { "creator_type": "author", "first_name": "Yuga", "last_name": "Hanaki", "name": null }, { "creator_type": "author", "first_name": "Hidemasa", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Sohta", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Sakumi", "last_name": "Nakagawa", "name": null }, { "creator_type": "author", "first_name": "Keigo", "last_name": "Tada", "name": null }, { "creator_type": "author", "first_name": "Hikari", "last_name": "Matsumoto", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Kimata", "name": null }, { "creator_type": "author", "first_name": "Yoshikatsu", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Minako", "last_name": "Ueda", "name": null } ], "identifiers": { "doi": { "normalized": "10.1101/2025.06.11.659190" }, "pmcid": { "normalized": null }, "pmid": { "normalized": null } }, "mesh": [], "publication": { "conference_name": null, "date": "2025-06-17", "date_precision": "day", "issue": null, "normalized_date": "2025-06-17", "pages": null, "proceedings_title": null, "publisher": null, "title": null, "volume": null, "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "A simple and versatile plasma membrane staining method for visualizing living cell morphology in reproductive tissues across diverse plant species", "url": "https://www.biorxiv.org/content/10.1101/2025.06.11.659190v1", "zotero": { "item_type": "preprint" } }, { "abstract": "Hormones play an essential role in the survival and maintenance of homeostasis. Steroid hormones are structurally and evolutionarily conserved across animals, insects, and plants. Brassinosteroids (BRs) are plant steroid hormones originally isolated from pollen grains. However, the molecular roles of BRs in plant reproduction remain unclear. Here, we show that biologically active BRs, brassinolide (BL) and castasterone (CS), are detected in pistils and accumulate in the pollen grains of Arabidopsis thaliana. In vitro incubation with BL promotes pollen tube capacitation and attraction to ovules. Furthermore, BL treatment elevates the expression of various reproductive genes in pollen tubes and ovules. Additionally, mutant ovules defective in BRI1 signaling show decreased guidance rates and abnormal development of the filiform apparatus in synergid cells. Overall, this study characterizes the molecular functions of both BL and CS in promoting pollen tube guidance by regulating gene expression in male and female reproductive tissues.", "classifications": [ { "id": "Ueda", "label": "Group Ueda", "parent": "Ueda", "type": "group" }, { "id": "Ueda", "label": "Team Ueda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Kumi", "last_name": "Matsuura-Tokita", "name": null }, { "creator_type": "author", "first_name": "Takamasa", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Kimata", "name": null }, { "creator_type": "author", "first_name": "Yumiko", "last_name": "Takebayashi", "name": null }, { "creator_type": "author", "first_name": "Minako", "last_name": "Ueda", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Nakano", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Sakakibara", "name": null }, { "creator_type": "author", "first_name": "Akihiko", "last_name": "Nakano", "name": null }, { "creator_type": "author", "first_name": "Tetsuya", "last_name": "Higashiyama", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.celrep.2025.115815" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "40541185" } }, "mesh": [ { "descriptor": "Arabidopsis", "descriptor_ui": "D017360", "major_topic": true }, { "descriptor": "Arabidopsis Proteins", "descriptor_ui": "D029681", "major_topic": false }, { "descriptor": "Brassinosteroids", "descriptor_ui": "D060406", "major_topic": true }, { "descriptor": "Cholestanols", "descriptor_ui": "D002777", "major_topic": false }, { "descriptor": "Flowers", "descriptor_ui": "D035264", "major_topic": false }, { "descriptor": "Gene Expression Regulation, Plant", "descriptor_ui": "D018506", "major_topic": true }, { "descriptor": "Ovule", "descriptor_ui": "D056771", "major_topic": false }, { "descriptor": "Pollen Tube", "descriptor_ui": "D053205", "major_topic": true }, { "descriptor": "Reproduction", "descriptor_ui": "D012098", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Steroids, Heterocyclic", "descriptor_ui": "D013260", "major_topic": false } ], "publication": { "conference_name": null, "date": "2025 Jun 17", "date_precision": "day", "issue": "", "normalized_date": "2025-06-17", "pages": "115815", "proceedings_title": null, "publisher": "", "title": "Cell reports", "volume": "", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Brassinosteroids promote pollen tube guidance by coordinating gene expression in male and female reproductive tissues.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Tissue growth and deformation result from the combined effects of various cellular events, including cell shape change, cell rearrangement, cell division, and cell death. Resolving and integrating these cellular events is essential for understanding the coordination of tissue-scale growth and deformation by individual cellular behaviors that are critical for morphogenesis, wound healing, and other collective cellular phenomena. For epithelial tissues composed of tightly connected cells, the texture tensor method provides a unified framework for quantifying tissue and cell strains by tracking individual cells in live imaging data. The corresponding kinematic relationships have been introduced in a hydrodynamic model that we previously reported. In this study, we quantitatively evaluated the kinematic equations proposed in the hydrodynamic model using experimental data from a growing Drosophila wing. To accomplish this, we introduced modified definitions of the texture tensor and confirmed that one of these modifications more accurately represents approximated cellular shapes without relying on ad hoc scaling factors. By utilizing the modified tensor, we demonstrated the compatibility of the strain rate tensors and the accuracy of both the kinematic and cell number density equations. These results cross-validate the modified texture analysis and the hydrodynamic model. Furthermore, the precision of the kinematic relationships achieved in this study provides a robust foundation for more advanced integration of modeling and experiment.", "classifications": [ { "id": "JPMJCR1923", "label": "JPMJCR1923", "researcher": "Satoshi Sawai", "type": "grant" }, { "id": "Ishihara", "label": "Group Ishihara", "parent": "Sawai", "type": "group" }, { "id": "Sawai", "label": "Group Sawai", "parent": "Sawai", "type": "group" }, { "id": "Sawai", "label": "Team Sawai", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Toshinori", "last_name": "Namba", "name": null }, { "creator_type": "author", "first_name": "Kaoru", "last_name": "Sugimura", "name": null }, { "creator_type": "author", "first_name": "Shuji", "last_name": "Ishihara", "name": null } ], "identifiers": { "doi": { "normalized": "10.1140/epje/s10189-025-00495-2" }, "pmcid": { "normalized": "PMC12167722" }, "pmid": { "normalized": "40517354" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Biomechanical Phenomena", "descriptor_ui": "D001696", "major_topic": false }, { "descriptor": "Drosophila", "descriptor_ui": "D004330", "major_topic": false }, { "descriptor": "Drosophila melanogaster", "descriptor_ui": "D004331", "major_topic": false }, { "descriptor": "Epithelial Cells", "descriptor_ui": "D004847", "major_topic": true }, { "descriptor": "Epithelium", "descriptor_ui": "D004848", "major_topic": false }, { "descriptor": "Hydrodynamics", "descriptor_ui": "D057446", "major_topic": false }, { "descriptor": "Models, Biological", "descriptor_ui": "D008954", "major_topic": true }, { "descriptor": "Morphogenesis", "descriptor_ui": "D009024", "major_topic": true }, { "descriptor": "Wings, Animal", "descriptor_ui": "D014921", "major_topic": false } ], "publication": { "conference_name": null, "date": "2025 Jun 15", "date_precision": "day", "issue": "6-7", "normalized_date": "2025-06-15", "pages": "31", "proceedings_title": null, "publisher": "", "title": "The European physical journal. E, Soft matter", "volume": "48", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "In vivo assessment of kinematic relationships for epithelial morphogenesis.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "CD79B, the target of polatuzumab vedotin-an anti-CD79B antibody-drug conjugate-has shown greater efficacy in activated B-cell-type diffuse large B-cell lymphoma (DLBCL) than in germinal center B-cell (GCB) type. However, the correlation between CD79B expression and the clinicopathological parameters in DLBCL remains unknown. We evaluated CD79B expression using the H-score (range: 0-300) in 379 samples from 280 patients with DLBCL. Low CD79B expression (H-score 100) CD79A and CD19 expression. No mutation in the first tyrosine residue of CD79B immunoreceptor tyrosine-based activation motif, Y196, was identified in DLBCL with low CD79B expression. Additionally, low CD79B expression was not associated with the co-occurrence of CD79B ITAM and MYD88 L265P mutations (P=0.748). Of the 78 patients with multiple biopsy specimens obtained from multiple sites or recurrent tumors, a change in CD79B expression from low to high or verse versa was observed in 9% of patients. In conclusion, CD79B expression was lower in the non-GCB type than in the GCB type. CD79B, CD79A, and CD19 expressions were not completely correlated, and one expression cannot predict the others. In 9% of patients, CD79B expression was inconsistent in multiple biopsy samples.", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yuto", "last_name": "Kaimi", "name": null }, { "creator_type": "author", "first_name": "Maki", "last_name": "Shibata", "name": null }, { "creator_type": "author", "first_name": "Suguru", "last_name": "Fukuhara", "name": null }, { "creator_type": "author", "first_name": "Yuka", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Tetsuro", "last_name": "Ochi", "name": null }, { "creator_type": "author", "first_name": "Shinichi", "last_name": "Makita", "name": null }, { "creator_type": "author", "first_name": "Noriko", "last_name": "Iwaki", "name": null }, { "creator_type": "author", "first_name": "Wataru", "last_name": "Munakata", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Izutsu", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null }, { "creator_type": "author", "first_name": "Akiko Miyagi", "last_name": "Maeshima", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.humpath.2025.105852" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "40523447" } }, "mesh": [ { "descriptor": "Adolescent", "descriptor_ui": "D000293", "major_topic": false }, { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Aged, 80 and over", "descriptor_ui": "D000369", "major_topic": false }, { "descriptor": "Antigens, CD19", "descriptor_ui": "D018941", "major_topic": true }, { "descriptor": "Biomarkers, Tumor", "descriptor_ui": "D014408", "major_topic": true }, { "descriptor": "CD79 Antigens", "descriptor_ui": "D051925", "major_topic": true }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Lymphoma, Large B-Cell, Diffuse", "descriptor_ui": "D016403", "major_topic": true }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": true }, { "descriptor": "Young Adult", "descriptor_ui": "D055815", "major_topic": false } ], "publication": { "conference_name": null, "date": "2025 Jun 14", "date_precision": "day", "issue": "", "normalized_date": "2025-06-14", "pages": "105852", "proceedings_title": null, "publisher": "", "title": "Human pathology", "volume": "", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Correlation with CD79B expression and clinicopathological parameters including cell of origin, CD79A and CD19 expression, and CD79B mutation in diffuse large B-cell lymphoma.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "INTRODUCTION: Up to 54% of all lung adenocarcinoma (LADC) cases in Asian populations occur in never-smoking women, suggesting that the impact of smoking and other environmental factors on the risk of early-onset LADC is minimal. Genetic factors may play a crucial role in disease development. METHODS: The prevalence of germline pathogenic variants (GPVs) of 454 hereditary cancer and DNA repair genes was examined by whole-exome and whole-genome sequencing of 350 early-onset LADC (aged < 40 years) and 1,441 later-onset LADC (aged >/= 41 years) cases. A case-control study comprising 10,672 LADC cases and 7,898 healthy controls was performed to identify moderate-risk genetic factors for the disease. Analysis of somatic mutations in 1,280 LADC patients, including 31 patients with GPVs, was also performed. RESULTS: The frequency of GPVs of TP53 and BRCA2 was significantly higher in those with early-onset LADC than in those with later-onset LADC. The detection rates for TP53 and BRCA2 GPVs were 2.9% and 1.7%, respectively, in patients with early-onset LADC, and 0.14% and 0.21%, respectively, in patients with later-onset LADC. Patients with BRCA1 GPVs showed a high incidence of concurrent TP53 somatic mutations. Patients with BRCA2 GPVs showed deficient homologous recombination in tumors via loss of the wild-type allele. A germline ALKBH2 variant, p.Glu35Alafs*54, was associated with the risk of early-onset LADC, and patients with a deleterious variant showed a correlation between SBS4-related somatic mutations and the Brinkman index. CONCLUSIONS: TP53 and BRCA2 GPVs and the ALKBH2 novel variant are associated with early-onset LADC in Asians.", "classifications": [ { "id": "Hamamoto", "label": "Group Hamamoto", "parent": "Okamoto", "type": "group" }, { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Hourin", "last_name": "Cho", "name": null }, { "creator_type": "author", "first_name": "Kouya", "last_name": "Shiraishi", "name": null }, { "creator_type": "author", "first_name": "Kuniko", "last_name": "Sunami", "name": null }, { "creator_type": "author", "first_name": "Yukihide", "last_name": "Momozawa", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Shingo", "last_name": "Matsumoto", "name": null }, { "creator_type": "author", "first_name": "Koichi", "last_name": "Matsuda", "name": null }, { "creator_type": "author", "first_name": "Motonobu", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Akiteru", "last_name": "Goto", "name": null }, { "creator_type": "author", "first_name": "Takayuki", "last_name": "Honda", "name": null }, { "creator_type": "author", "first_name": "Akifumi", "last_name": "Mochizuki", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Torasawa", "name": null }, { "creator_type": "author", "first_name": "Yataro", "last_name": "Daigo", "name": null }, { "creator_type": "author", "first_name": "Kimihiro", "last_name": "Shimizu", "name": null }, { "creator_type": "author", "first_name": "Hideo", "last_name": "Kunitoh", "name": null }, { "creator_type": "author", "first_name": "Yukihiro", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Hirata", "name": null }, { "creator_type": "author", "first_name": "Yoko", "last_name": "Shimada", "name": null }, { "creator_type": "author", "first_name": "Michiko", "last_name": "Ueki", "name": null }, { "creator_type": "author", "first_name": "Hanako", "last_name": "Ono", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Gotoh", "name": null }, { "creator_type": "author", "first_name": "Yukiko Shimoda", "last_name": "Igawa", "name": null }, { "creator_type": "author", "first_name": "Akiko", "last_name": "Tateishi", "name": null }, { "creator_type": "author", "first_name": "Yoh", "last_name": "Yamaguchi", "name": null }, { "creator_type": "author", "first_name": "Ryoko Inaba", "last_name": "Higashiyama", "name": null }, { "creator_type": "author", "first_name": "Erika", "last_name": "Machida", "name": null }, { "creator_type": "author", "first_name": "Motoki", "last_name": "Iwasaki", "name": null }, { "creator_type": "author", "first_name": "Yosuke", "last_name": "Kawai", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Yasuda", "name": null }, { "creator_type": "author", "first_name": "Junko", "last_name": "Hamamoto", "name": null }, { "creator_type": "author", "first_name": "Issei", "last_name": "Imoto", "name": null }, { "creator_type": "author", "first_name": "Hirokazu", "last_name": "Matsushita", "name": null }, { "creator_type": "author", "first_name": "Sadaaki", "last_name": "Takata", "name": null }, { "creator_type": "author", "first_name": "Tomomi", "last_name": "Aoi", "name": null }, { "creator_type": "author", "first_name": "Syuzo", "last_name": "Kaneko", "name": null }, { "creator_type": "author", "first_name": "Aya", "last_name": "Kuchiba", "name": null }, { "creator_type": "author", "first_name": "Akihiko", "last_name": "Shimomura", "name": null }, { "creator_type": "author", "first_name": "Maki", "last_name": "Fukami", "name": null }, { "creator_type": "author", "first_name": "Kotaro", "last_name": "Hattori", "name": null }, { "creator_type": "author", "first_name": "Kouichi", "last_name": "Ozaki", "name": null }, { "creator_type": "author", "first_name": "Yoshihiro", "last_name": "Asano", "name": null }, { "creator_type": "author", "first_name": "Biobank Japan", "last_name": "Project", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Takano", "name": null }, { "creator_type": "author", "first_name": "Masashi", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Yohei", "last_name": "Miyagi", "name": null }, { "creator_type": "author", "first_name": "Kazumi", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Takumi", "last_name": "Yamaura", "name": null }, { "creator_type": "author", "first_name": "Teruhiko", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Goto", "name": null }, { "creator_type": "author", "first_name": "Hidehito", "last_name": "Horinouchi", "name": null }, { "creator_type": "author", "first_name": "Yasunari", "last_name": "Miyazaki", "name": null }, { "creator_type": "author", "first_name": "Hidemi", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Toshiteru", "last_name": "Nagashima", "name": null }, { "creator_type": "author", "first_name": "Yoichi", "last_name": "Ohtaki", "name": null }, { "creator_type": "author", "first_name": "Kazuhiro", "last_name": "Imai", "name": null }, { "creator_type": "author", "first_name": "Yoshihiro", "last_name": "Minamiya", "name": null }, { "creator_type": "author", "first_name": "Kenichi", "last_name": "Okubo", "name": null }, { "creator_type": "author", "first_name": "Johji", "last_name": "Inazawa", "name": null }, { "creator_type": "author", "first_name": "Yuichi", "last_name": "Shiraishi", "name": null }, { "creator_type": "author", "first_name": "Katsushi", "last_name": "Tokunaga", "name": null }, { "creator_type": "author", "first_name": "Yoichiro", "last_name": "Kamatani", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null }, { "creator_type": "author", "first_name": "Koichi", "last_name": "Goto", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Tsuboi", "name": null }, { "creator_type": "author", "first_name": "Shun-Ichi", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Yuichiro", "last_name": "Ohe", "name": null }, { "creator_type": "author", "first_name": "Yoshinori", "last_name": "Murakami", "name": null }, { "creator_type": "author", "first_name": "Keitaro", "last_name": "Matsuo", "name": null }, { "creator_type": "author", "first_name": "Ryuji", "last_name": "Hamamoto", "name": null }, { "creator_type": "author", "first_name": "Takahshi", "last_name": "Kohno", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.jtho.2025.06.005" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "40516820" } }, "mesh": [ { "descriptor": "Adenocarcinoma of Lung", "descriptor_ui": "D000077192", "major_topic": true }, { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Age of Onset", "descriptor_ui": "D017668", "major_topic": false }, { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "BRCA2 Protein", "descriptor_ui": "D024682", "major_topic": false }, { "descriptor": "Case-Control Studies", "descriptor_ui": "D016022", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Genetic Predisposition to Disease", "descriptor_ui": "D020022", "major_topic": false }, { "descriptor": "Germ-Line Mutation", "descriptor_ui": "D018095", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Lung Neoplasms", "descriptor_ui": "D008175", "major_topic": true }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Penetrance", "descriptor_ui": "D019683", "major_topic": false }, { "descriptor": "Prognosis", "descriptor_ui": "D011379", "major_topic": false } ], "publication": { "conference_name": null, "date": "2025 Jun 12", "date_precision": "day", "issue": "", "normalized_date": "2025-06-12", "pages": "S1556-0864(25)00764-6", "proceedings_title": null, "publisher": "", "title": "Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer", "volume": "", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Genomic profiles of pathogenic and moderate-penetrance germline variants associated with risk of early-onset lung adenocarcinoma.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Near-infrared (NIR) fluorescence probes for hypochlorous acid (HClO) are powerful tools for investigating various biological phenomena because of their low autofluorescence, high tissue penetration and usefulness for multicolour imaging. Here we present a rational probe design strategy based on the phenyl-induced twisted intramolecular charge transfer (p-TICT) mechanism and apply it to develop a NIR fluorescence probe for HClO, N-Phenol SiR1. This probe was applied for multicolor (4 colors) live-cell fluorescence imaging, occupying the NIR color window.", "classifications": [ { "id": "Kuchimaru", "label": "Group Kuchimaru", "parent": "Shintaku", "type": "group" }, { "id": "Shintaku", "label": "Team Shintaku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Hisashi", "last_name": "Ohno", "name": null }, { "creator_type": "author", "first_name": "Shun", "last_name": "Sumitani", "name": null }, { "creator_type": "author", "first_name": "Ariunbold", "last_name": "Chuluun-Erdene", "name": null }, { "creator_type": "author", "first_name": "Takahiro", "last_name": "Kuchimaru", "name": null }, { "creator_type": "author", "first_name": "Sota", "last_name": "Yamada", "name": null }, { "creator_type": "author", "first_name": "Eita", "last_name": "Sasaki", "name": null }, { "creator_type": "author", "first_name": "Kenjiro", "last_name": "Hanaoka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1039/d5cc02212f" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "40497359" } }, "mesh": [], "publication": { "conference_name": null, "date": "2025 Jun 11", "date_precision": "day", "issue": "", "normalized_date": "2025-06-11", "pages": "", "proceedings_title": null, "publisher": "", "title": "Chemical communications (Cambridge, England)", "volume": "", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Development of a near-infrared fluorescence probe for hypochlorous acid based on the phenyl-induced twisted intramolecular charge transfer (p-TICT) mechanism.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The ring finger protein 213 (RNF213) gene, identified in 2011 as a susceptibility gene for moyamoya disease (MMD), has since been recognized as a key factor in a broader spectrum of vascular disorders. The p.R4810K mutation in RNF213 is particularly common among Japanese MMD patients, although a smaller percentage of healthy individuals also carry the mutation, indicating that environmental factors, alongside genetic predisposition, likely influence disease onset. RNF213, a large E3 ubiquitin ligase, plays essential roles in vascular homeostasis, immune response, and endoplasmic reticulum stress reaction. Its mutation disrupts normal angiogenesis, contributing to abnormal vascular remodeling in conditions such as pulmonary hypertension and coronary artery disease. This review examines the multifaceted role of RNF213 and its p.R4810K mutation in the pathogenesis of MMD and other vascular conditions, collectively referred to as RNF213-associated vascular diseases. While research has begun to clarify the mutation's effects on angiogenesis and the involved pathways, the roles of RNF213 and its mutation in vascular integrity remain unclear. This comprehensive overview underscores the complex interaction between genetic and environmental factors in RNF213-related vascular diseases and calls for further research to elucidate these mechanisms and develop targeted therapeutic interventions.", "classifications": [ { "id": "Kuchimaru", "label": "Group Kuchimaru", "parent": "Shintaku", "type": "group" }, { "id": "Shintaku", "label": "Team Shintaku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Toshinaru", "last_name": "Kawakami", "name": null }, { "creator_type": "author", "first_name": "Masamichi", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Takayuki", "last_name": "Isagawa", "name": null }, { "creator_type": "author", "first_name": "Takahiro", "last_name": "Kuchimaru", "name": null }, { "creator_type": "author", "first_name": "Norihiko", "last_name": "Takeda", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.jjcc.2025.06.001" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "40505810" } }, "mesh": [ { "descriptor": "Adenosine Triphosphatases", "descriptor_ui": "D000251", "major_topic": true }, { "descriptor": "Cardiovascular Diseases", "descriptor_ui": "D002318", "major_topic": true }, { "descriptor": "Genetic Predisposition to Disease", "descriptor_ui": "D020022", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Moyamoya Disease", "descriptor_ui": "D009072", "major_topic": false }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": false }, { "descriptor": "Ubiquitin-Protein Ligases", "descriptor_ui": "D044767", "major_topic": true } ], "publication": { "conference_name": null, "date": "2025 Jun 10", "date_precision": "day", "issue": "", "normalized_date": "2025-06-10", "pages": "S0914-5087(25)00145-5", "proceedings_title": null, "publisher": "", "title": "Journal of cardiology", "volume": "", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "RNF213 and cardiovascular disease: a review of histopathological, genetic perspectives, and potential molecular mechanisms.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "", "classifications": [ { "id": "Tsugawa", "label": "Group Tsugawa", "parent": "Ueda", "type": "group" }, { "id": "Ueda", "label": "Team Ueda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yuki", "last_name": "Yamasaki", "name": null }, { "creator_type": "author", "first_name": "Kazunori", "last_name": "Okano", "name": null }, { "creator_type": "author", "first_name": "Tetsuro", "last_name": "Mimura", "name": null }, { "creator_type": "author", "first_name": "Satoru", "last_name": "Tsugawa", "name": null }, { "creator_type": "author", "first_name": "Yoichiroh", "last_name": "Hosokawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/s00425-025-04738-6" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "40488906" } }, "mesh": [], "publication": { "conference_name": null, "date": "2025 Jun 9", "date_precision": "day", "issue": "1", "normalized_date": "2025-06-09", "pages": "19", "proceedings_title": null, "publisher": "", "title": "Planta", "volume": "262", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Correction: Simultaneous quantification of cell wall elasticity and turgor pressure in live plant cells by elastic shell theory analysis and AFM.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "We established a novel knock-in technique, New and Easy Xenopus Targeted integration (NEXTi), to recapitulate endogenous gene expression by reporter expression. NEXTi is a CRISPR-Cas9-based method to integrate a donor DNA containing a reporter gene (egfp) into the target 5' untranslated region (UTR) of the Xenopus laevis genome. It enables us to track eGFP expression under the regulation of endogenous promoter/enhancer activities. We obtained about 2% to 13% of knock-in vector-injected embryos showing eGFP signal in a tissue-specific manner, targeting krt.12.2.L, myod1.S, sox2.L, and bcan.S loci, as previously reported. In addition, F1 embryos which show stable eGFP signals were obtained by outcrossing the matured injected frogs with wild-type animals. Integrations of donor DNAs into target 5' UTRs were confirmed by PCR amplification and sequencing. Here, we describe the step-by-step protocol for preparation of donor DNA and single guide RNA, microinjection, and genotyping of F1 animals for the NEXTi procedure.", "classifications": [ { "id": "Suzuki", "label": "Group Suzuki", "parent": "Morishita", "type": "group" }, { "id": "Morishita", "label": "Team Morishita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Norie", "last_name": "Kagawa", "name": null }, { "creator_type": "author", "first_name": "Yoshihiko", "last_name": "Umesono", "name": null }, { "creator_type": "author", "first_name": "Ken-Ichi T.", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Mochii", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/dgd.70011" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "40490360" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "CRISPR-Cas Systems", "descriptor_ui": "D064113", "major_topic": false }, { "descriptor": "Gene Knock-In Techniques", "descriptor_ui": "D055879", "major_topic": true }, { "descriptor": "Green Fluorescent Proteins", "descriptor_ui": "D049452", "major_topic": false }, { "descriptor": "Xenopus laevis", "descriptor_ui": "D014982", "major_topic": true } ], "publication": { "conference_name": null, "date": "2025 Jun 9", "date_precision": "day", "issue": "", "normalized_date": "2025-06-09", "pages": "", "proceedings_title": null, "publisher": "", "title": "Development, growth & differentiation", "volume": "", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Step-by-Step Protocol for Making a Knock-In Xenopus laevis to Visualize Endogenous Gene Expression.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Live-cell imaging has enabled the visualization of cytoskeletal dynamics with high spatiotemporal resolution, producing vast, and complex datasets. Recent advancements in live-cell imaging techniques have significantly increased data dimensionality and throughput, challenging conventional qualitative analysis methods. Computational approaches, including machine learning-based image processing, have emerged as powerful tools for extracting quantitative features from these datasets, facilitating systematic analysis of cytoskeletal organization and dynamics. In this review, we outline image analysis techniques for quantification of cytoskeletal structures, focusing on microscopic image transformation and feature extraction. We discuss classical image-processing methods, such as filtering and segmentation, as well as recent applications of deep learning in cytoskeletal analysis. Furthermore, we revisit classical studies on cortical microtubule reorganization after plant cytokinesis, and explore how modern computational techniques can provide new insights into traditional concepts.", "classifications": [ { "id": "Higaki", "label": "Group Higaki", "parent": "Ueda", "type": "group" }, { "id": "Ueda", "label": "Team Ueda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Haruka", "last_name": "Ono", "name": null }, { "creator_type": "author", "first_name": "Takumi", "last_name": "Higaki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/cm.22049" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "40474669" } }, "mesh": [ { "descriptor": "Cytoskeleton", "descriptor_ui": "D003599", "major_topic": true }, { "descriptor": "Image Processing, Computer-Assisted", "descriptor_ui": "D007091", "major_topic": true }, { "descriptor": "Microtubules", "descriptor_ui": "D008870", "major_topic": false }, { "descriptor": "Plants", "descriptor_ui": "D010944", "major_topic": true } ], "publication": { "conference_name": null, "date": "2025 Jun 6", "date_precision": "day", "issue": "", "normalized_date": "2025-06-06", "pages": "", "proceedings_title": null, "publisher": "", "title": "Cytoskeleton (Hoboken, N.J.)", "volume": "", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Computational Approaches to Revisiting Plant Cytoskeleton Organization and Dynamics.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Quadruple stacking topology with an unusual threefold stacking periodicity in four honeycomb sheets was realized in a flexible wavy honeycomb-sheet MOF (PMC-20). The infinite pi-stacked arrays, formed exclusively at the pi-conjugated core of the linker site, contribute to the highest electrical conductivity among the reported naphthalenediimide (NDI)-based crystals.", "classifications": [ { "id": "Hijikata", "label": "Group Hijikata", "parent": "Tsuchiya", "type": "group" }, { "id": "Tsuchiya", "label": "Team Tsuchiya", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Tappei", "last_name": "Tanabe", "name": null }, { "creator_type": "author", "first_name": "Liyuan", "last_name": "Qu", "name": null }, { "creator_type": "author", "first_name": "Kenta", "last_name": "Ueno", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Takaishi", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Yamashita", "name": null }, { "creator_type": "author", "first_name": "Yuh", "last_name": "Hijikata", "name": null }, { "creator_type": "author", "first_name": "Ryotaro", "last_name": "Matsuda", "name": null }, { "creator_type": "author", "first_name": "Ryota", "last_name": "Sakamoto", "name": null }, { "creator_type": "author", "first_name": "Hiroaki", "last_name": "Iguchi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1039/d5cc00084j" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "40455406" } }, "mesh": [], "publication": { "conference_name": null, "date": "2025 Jun 2", "date_precision": "day", "issue": "", "normalized_date": "2025-06-02", "pages": "", "proceedings_title": null, "publisher": "", "title": "Chemical communications (Cambridge, England)", "volume": "", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Uncommon quadruple stacking topology in a honeycomb-sheet MOF compatible with through-space conduction.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "PURPOSE: Adjuvant osimertinib is standard-of-care for patients with resected epidermal growth factor receptor (EGFR)-mutated non-small-cell lung cancer (NSCLC). Neoadjuvant treatment could improve surgical and long-term outcomes. METHODS: In this randomized, controlled, phase 3 study, patients with resectable, EGFR-mutated, stage II-IIIB NSCLC were randomly assigned (1:1:1) to receive neoadjuvant osimertinib (80 mg orally once daily for >/=9 weeks) plus platinum-based chemotherapy (every 3 weeks for three cycles), osimertinib monotherapy (for >/=9 weeks), or placebo plus platinum-based chemotherapy (control), followed by surgical resection. Adjuvant osimertinib was offered to eligible patients after completion of surgery. The primary endpoint was major pathological response (MPR) by blinded central pathology review. Event-free survival (EFS) was a secondary endpoint. RESULTS: Overall, 358 patients were randomized to receive osimertinib-plus-chemotherapy (121 patients), osimertinib-monotherapy (117 patients), or placebo-plus-chemotherapy (120 patients). Osimertinib-plus-chemotherapy (MPR rate 26%) and osimertinib-monotherapy (25%) demonstrated statistically significant improvement in the MPR rate versus placebo-plus-chemotherapy (2%), with corresponding odds ratios of 19.82 (95.002% confidence interval [CI], 4.60, 85.33; p<0.0001) and 19.28 (99.9% CI, 1.71, 217.39; p<0.0001), respectively. With 15% data maturity, the EFS rates at 12 months were 93%, 95%, and 83% with osimertinib-plus-chemotherapy, osimertinib-monotherapy, and placebo-plus-chemotherapy, respectively. In the neoadjuvant period, grade >/=3 adverse events of any cause occurred in 36%, 13%, and 33% of patients with osimertinib-plus-chemotherapy, osimertinib-monotherapy, and placebo-plus-chemotherapy, respectively. No new safety concerns were identified. CONCLUSION: Neoadjuvant osimertinib with or without chemotherapy demonstrated statistically significant improvement in the MPR rate over chemotherapy alone in patients with resectable, EGFR-mutated, stage II-IIIB NSCLC.", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Jianxing", "last_name": "He", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Tsuboi", "name": null }, { "creator_type": "author", "first_name": "Walter", "last_name": "Weder", "name": null }, { "creator_type": "author", "first_name": "Ke-Neng", "last_name": "Chen", "name": null }, { "creator_type": "author", "first_name": "Maximilian J.", "last_name": "Hochmair", "name": null }, { "creator_type": "author", "first_name": "Jin-Yuan", "last_name": "Shih", "name": null }, { "creator_type": "author", "first_name": "Sung Yong", "last_name": "Lee", "name": null }, { "creator_type": "author", "first_name": "Kang-Yun", "last_name": "Lee", "name": null }, { "creator_type": "author", "first_name": "Nguyen Viet", "last_name": "Nhung", "name": null }, { "creator_type": "author", "first_name": "Somcharoen", "last_name": "Saeteng", "name": null }, { "creator_type": "author", "first_name": "Lunxu", "last_name": "Liu", "name": null }, { "creator_type": "author", "first_name": "Ligang", "last_name": "Xing", "name": null }, { "creator_type": "author", "first_name": "Nguyen Hoang", "last_name": "Gia", "name": null }, { "creator_type": "author", "first_name": "Shuji", "last_name": "Murakami", "name": null }, { "creator_type": "author", "first_name": "Yongtao", "last_name": "Han", "name": null }, { "creator_type": "author", "first_name": "Maria Paz", "last_name": "Saavedra", "name": null }, { "creator_type": "author", "first_name": "Seong Hoon", "last_name": "Yoon", "name": null }, { "creator_type": "author", "first_name": "Carlos H. A.", "last_name": "Teixeira", "name": null }, { "creator_type": "author", "first_name": "Carles", "last_name": "Escriu", "name": null }, { "creator_type": "author", "first_name": "Alex", "last_name": "Martinez-Marti", "name": null }, { "creator_type": "author", "first_name": "Collin M.", "last_name": "Blakely", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null }, { "creator_type": "author", "first_name": "Sanja", "last_name": "Dacic", "name": null }, { "creator_type": "author", "first_name": "Yuri", "last_name": "Rukazenkov", "name": null }, { "creator_type": "author", "first_name": "Xiangning", "last_name": "Huang", "name": null }, { "creator_type": "author", "first_name": "Anupriya", "last_name": "Dayal", "name": null }, { "creator_type": "author", "first_name": "Jamie E.", "last_name": "Chaft", "name": null } ], "identifiers": { "doi": { "normalized": "10.1200/jco-25-00883" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "40454705" } }, "mesh": [ { "descriptor": "Acrylamides", "descriptor_ui": "D000178", "major_topic": true }, { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Aniline Compounds", "descriptor_ui": "D000814", "major_topic": true }, { "descriptor": "Antineoplastic Combined Chemotherapy Protocols", "descriptor_ui": "D000971", "major_topic": true }, { "descriptor": "Carcinoma, Non-Small-Cell Lung", "descriptor_ui": "D002289", "major_topic": true }, { "descriptor": "Double-Blind Method", "descriptor_ui": "D004311", "major_topic": false }, { "descriptor": "ErbB Receptors", "descriptor_ui": "D066246", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Indoles", "descriptor_ui": "D007211", "major_topic": false }, { "descriptor": "Lung Neoplasms", "descriptor_ui": "D008175", "major_topic": true }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": true }, { "descriptor": "Neoadjuvant Therapy", "descriptor_ui": "D020360", "major_topic": false }, { "descriptor": "Pyrimidines", "descriptor_ui": "D011743", "major_topic": false } ], "publication": { "conference_name": null, "date": "2025 Jun 2", "date_precision": "day", "issue": "", "normalized_date": "2025-06-02", "pages": "101200JCO2500883", "proceedings_title": null, "publisher": "", "title": "Journal of clinical oncology : official journal of the American Society of Clinical Oncology", "volume": "", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Neoadjuvant Osimertinib for Resectable EGFR-Mutated Non-Small-Cell Lung Cancer.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Vertebrate glycerophospholipids typically exhibit a glycerol-3-phosphate (G3P)-configured backbone corresponding to the R-configured stereoisomer at the sn-2 chiral center. We previously found that the lysoglycerophospholipid lyso-phosphatidyl-beta-D-glucoside (LysoPtdGlc) with G3P-configuration, R-LysoPtdGlc, is an endogenous ligand of the G protein-coupled receptor GPR55, acting as an axon guidance cue via GPR55/Galpha(13) signaling. However, LysoPtdGlc is hydrolytically derived from phosphatidyl-beta-D-glucoside (PtdGlc) that exists in vivo in a 6:1 mixture of two stereoisomers, G3P-configured R-PtdGlc and glycerol-1-phosphate (G1P)-configured S-PtdGlc. To test whether the stereoconfiguration of LysoPtdGlc influences its biological activity, we combined molecular dynamics (MD) simulations of GPR55 activation by R-LysoPtdGlc and S-LysoPtdGlc with in vitro and in vivo biological assays of GPR55-mediated functions in nervous system. MD simulations predicted that R-LysoPtdGlc, but not S-LysoPtdGlc, remained in the putative ligand binding pocket of the GPR55/Galpha(13) complex. Utilizing our previously established synthetic access to R-LysoPtdGlc and S-LysoPtdGlc, we investigated in vitro axonal chemotropic responses to these two stereoisomers. We observed R-LysoPtdGlc-mediated chemorepulsion corroborating our previous studies, and unexpectedly, S-LysoPtdGlc-induced chemoattraction via GPR55/Galpha(S). Since these phenomena were observed in nociceptive neurons, we tested whether intrathecal administration of R-LysoPtdGlc or S-LysoPtdGlc induced a nociceptive phenotype in adult mice and found that R-LysoPtdGlc but not S-LysoPtdGlc increased behavioral sensitivity to mechanical stimuli, and that this response was dependent on GPR55. These data indicate that the stereoconfiguration of LysoPtdGlc determines its biological activity and suggest, at least in vitro, LysoPtdGlc stereoisomers exert distinct GPR55-mediated functions via different Galpha subunits.", "classifications": [ { "id": "Imayoshi", "label": "Group Imayoshi", "parent": "Imayoshi", "type": "group" }, { "id": "Imayoshi", "label": "Team Imayoshi", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Adam T.", "last_name": "Guy", "name": null }, { "creator_type": "author", "first_name": "Yuta", "last_name": "Kohro", "name": null }, { "creator_type": "author", "first_name": "Koki", "last_name": "Kano", "name": null }, { "creator_type": "author", "first_name": "Xianyue", "last_name": "Huang", "name": null }, { "creator_type": "author", "first_name": "Linchi", "last_name": "Chen", "name": null }, { "creator_type": "author", "first_name": "Noriko", "last_name": "Ooashi", "name": null }, { "creator_type": "author", "first_name": "Mariko", "last_name": "Inoue", "name": null }, { "creator_type": "author", "first_name": "Nozomi", "last_name": "Ishii", "name": null }, { "creator_type": "author", "first_name": "Tomohiro", "last_name": "Yamashita", "name": null }, { "creator_type": "author", "first_name": "Yoshio", "last_name": "Hirabayashi", "name": null }, { "creator_type": "author", "first_name": "Itaru", "last_name": "Imayoshi", "name": null }, { "creator_type": "author", "first_name": "Ichiro", "last_name": "Matsuo", "name": null }, { "creator_type": "author", "first_name": "Peter", "last_name": "Greimel", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Tsuda", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Kamiguchi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.jbc.2025.110324" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "40451430" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "HEK293 Cells", "descriptor_ui": "D057809", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Lysophospholipids", "descriptor_ui": "D008246", "major_topic": true }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Molecular Dynamics Simulation", "descriptor_ui": "D056004", "major_topic": false }, { "descriptor": "Receptors, Cannabinoid", "descriptor_ui": "D043882", "major_topic": true }, { "descriptor": "Receptors, G-Protein-Coupled", "descriptor_ui": "D043562", "major_topic": true }, { "descriptor": "Stereoisomerism", "descriptor_ui": "D013237", "major_topic": false } ], "publication": { "conference_name": null, "date": "2025 May 30", "date_precision": "day", "issue": "", "normalized_date": "2025-05-30", "pages": "110324", "proceedings_title": null, "publisher": "", "title": "The Journal of biological chemistry", "volume": "", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Lysophospholipid stereoisomers exert distinct GPR55-mediated functions via different Galpha subunits.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Heme oxygenase-1 (HO-1) is unique to be directly regulated by diverse stress-responsible transcription factors, however, the cross-talk between oxidative stress and heat shock stress has not been completely elucidated. It is widely accepted that HO activity is not induced by heat shock in cultured cells derived from humans and mice but from rats. Previously, we reported that the discrepancies in heat shock-induced HO-1 expression in different animal species were caused by the access of heat shock factor 1 (HSF1) to heat shock element (HSE) in the different region of the HO-1 gene. Recently, we found that the human monocyte-derived cell line THP-1, which has been extensively used to study monocyte/macrophage functions, represents the heat shock induction of HO-1 after differentiation to macrophage-like cells, although not responsible before differentiation. In this study, we demonstrated that heat shock loading to macrophage-like cells derived from THP-1 specifically activated HSF1 to bind to HSE in the promotor region in the HO-1 gene, resulting in the induction of HO-1. Our finding is significant in understanding the regulation system by macrophages for inflammation caused by oxidative insults and associated with hyperthermia in vivo.", "classifications": [ { "id": "Miyamoto", "label": "Group Miyamoto", "parent": "Wakamoto", "type": "group" }, { "id": "Wakamoto", "label": "Team Wakamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Daisuke", "last_name": "Tsuji", "name": null }, { "creator_type": "author", "first_name": "Nodoka", "last_name": "Ishida", "name": null }, { "creator_type": "author", "first_name": "Takafumi", "last_name": "Miyamoto", "name": null }, { "creator_type": "author", "first_name": "Sachiye", "last_name": "Inouye", "name": null }, { "creator_type": "author", "first_name": "Reiko", "last_name": "Akagi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1093/jb/mvaf029" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "40445146" } }, "mesh": [ { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": true }, { "descriptor": "DNA-Binding Proteins", "descriptor_ui": "D004268", "major_topic": false }, { "descriptor": "Heat Shock Transcription Factors", "descriptor_ui": "D000076249", "major_topic": false }, { "descriptor": "Heat-Shock Response", "descriptor_ui": "D018869", "major_topic": true }, { "descriptor": "Heme Oxygenase-1", "descriptor_ui": "D051547", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Macrophages", "descriptor_ui": "D008264", "major_topic": true }, { "descriptor": "Monocytes", "descriptor_ui": "D009000", "major_topic": true }, { "descriptor": "THP-1 Cells", "descriptor_ui": "D000074084", "major_topic": false }, { "descriptor": "Transcription Factors", "descriptor_ui": "D014157", "major_topic": false } ], "publication": { "conference_name": null, "date": "2025 May 30", "date_precision": "day", "issue": "", "normalized_date": "2025-05-30", "pages": "mvaf029", "proceedings_title": null, "publisher": "", "title": "Journal of biochemistry", "volume": "", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Acquisition mechanism of heme oxygenase-1 induction by heat shock in human monocytic cell line THP-1 after differentiation to macrophage-like cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Human trophoblast stem cells (TSCs) can self-renew and differentiate into major trophoblast lineages. Although TSC-like cells can be derived from both naive and primed pluripotent stem cells (PSCs), the mechanisms governing the conversion of PSCs into a TSC state remain only partially understood. This study explored the cellular properties of primed PSC-derived trophoblast stem-like cells (TSLCs) and the molecular processes underlying the PSC-to-TSLC conversion. We first induced GATA3(+) cells from primed PSCs using small molecule inhibitors and then cultured them under defined TSC maintenance conditions. The resulting TSLCs exhibited transcriptomic similarity to established TSCs and villous cytotrophoblasts from the human first-trimester placenta and demonstrated bipotency toward major trophoblast subtypes. Notably, while GATA3(+) cells lack self-renewal capacity, the TSC culture conditions facilitate their conversion into self-renewing TSLCs. Furthermore, the transcription factor TFAP2C was identified as essential for imparting self-renewal capacity to GATA3(+) cells. These findings demonstrate that TSLC derivation from primed PSCs involves two distinct processes: trophoblast lineage fate conversion and self-renewal capacity acquisition, the latter of which is specifically dependent on TFAP2C.", "classifications": [ { "id": "Eiraku", "label": "Group Eiraku", "parent": "Eiraku", "type": "group" }, { "id": "Eiraku", "label": "Team Eiraku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Masatoshi", "last_name": "Ohgushi", "name": null }, { "creator_type": "author", "first_name": "Kaori", "last_name": "Honda", "name": null }, { "creator_type": "author", "first_name": "Rina", "last_name": "Takagi", "name": null }, { "creator_type": "author", "first_name": "Mototsugu", "last_name": "Eiraku", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41598-025-03830-x" }, "pmcid": { "normalized": "PMC12125314" }, "pmid": { "normalized": "40447714" } }, "mesh": [ { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Cell Lineage", "descriptor_ui": "D019070", "major_topic": false }, { "descriptor": "Cell Self Renewal", "descriptor_ui": "D000066673", "major_topic": true }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Embryonic Stem Cells", "descriptor_ui": "D053595", "major_topic": true }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "GATA3 Transcription Factor", "descriptor_ui": "D050990", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Placenta", "descriptor_ui": "D010920", "major_topic": false }, { "descriptor": "Pregnancy", "descriptor_ui": "D011247", "major_topic": false }, { "descriptor": "Transcription Factor AP-2", "descriptor_ui": "D050656", "major_topic": true }, { "descriptor": "Trophoblasts", "descriptor_ui": "D014327", "major_topic": true } ], "publication": { "conference_name": null, "date": "2025 May 30", "date_precision": "day", "issue": "1", "normalized_date": "2025-05-30", "pages": "19040", "proceedings_title": null, "publisher": "", "title": "Scientific reports", "volume": "15", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Stepwise strategy for generating human trophoblast stem-like cells from embryonic stem cells reveals specific role of TFAP2C in acquiring self-renewability.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Satsuki", "last_name": "Kishikawa", "name": null }, { "creator_type": "author", "first_name": "Seiji", "last_name": "Tsuruta", "name": null }, { "creator_type": "author", "first_name": "Eiji", "last_name": "Nakano", "name": null }, { "creator_type": "author", "first_name": "Dai", "last_name": "Ogata", "name": null }, { "creator_type": "author", "first_name": "Kenjiro", "last_name": "Namikawa", "name": null }, { "creator_type": "author", "first_name": "Naoya", "last_name": "Yamazaki", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null }, { "creator_type": "author", "first_name": "Taisuke", "last_name": "Mori", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/cup.14825" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "40436435" } }, "mesh": [], "publication": { "conference_name": null, "date": "2025 May 28", "date_precision": "day", "issue": "", "normalized_date": "2025-05-28", "pages": "", "proceedings_title": null, "publisher": "", "title": "Journal of cutaneous pathology", "volume": "", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Merkel Cell Carcinosarcoma: Wnt Pathway Activation Associated With Sarcomatoid Transformation.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The spatiotemporal heterogeneity in intratumor proliferative behavior of cancer cells deeply affects tumor environment characteristics and the efficacy of anticancer treatments. Thus, intravital imaging with unlimited imaging depth and cellular-level resolution is greatly desired. We developed an optical-fiber-bundle-based microendoscope with a genetically encoded fluorescent ubiquitination-based cell-cycle indicator (Fucci) system to achieve the intravital, periodic, and multicolor end-to-end imaging of the proliferative activity of cancer cells at a cellular-level resolution. This technique enabled the periodic visualization of spatiotemporal cellular responses, including cell-cycle arrest and resumption, and nuclear enlargement following the administration of anticancer drugs in living mice. It was suggested that proliferating cell ratio and nuclear enlargement in cancer cells at the surface region of tumor characterized by abundant vascular invasion contribute to aggressive tumor regrowth after chemotherapy. The application of this technique can accelerate innovation in cancer biology and therapeutics.", "classifications": [ { "id": "JPMJCR2124", "label": "JPMJCR2124", "researcher": "Hirofumi Shintaku", "type": "grant" }, { "id": "Sawano", "label": "Group Sawano", "parent": "Shintaku", "type": "group" }, { "id": "Shintaku", "label": "Group Shintaku", "parent": "Shintaku", "type": "group" }, { "id": "Shintaku", "label": "Team Shintaku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Toshiyuki", "last_name": "Goto", "name": null }, { "creator_type": "author", "first_name": "Masayuki", "last_name": "Nakano", "name": null }, { "creator_type": "author", "first_name": "Sally", "last_name": "Danno", "name": null }, { "creator_type": "author", "first_name": "Chie", "last_name": "Ueda", "name": null }, { "creator_type": "author", "first_name": "Asako", "last_name": "Sakaue-Sawano", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Miyawaki", "name": null }, { "creator_type": "author", "first_name": "Anna", "last_name": "Wrabel", "name": null }, { "creator_type": "author", "first_name": "Ichiro", "last_name": "Nakahara", "name": null }, { "creator_type": "author", "first_name": "Takahito", "last_name": "Nishikata", "name": null }, { "creator_type": "author", "first_name": "Akira", "last_name": "Mizoguchi", "name": null }, { "creator_type": "author", "first_name": "Yasuhisa", "last_name": "Tamura", "name": null }, { "creator_type": "author", "first_name": "Kei", "last_name": "Mizuno", "name": null }, { "creator_type": "author", "first_name": "Yosky", "last_name": "Kataoka", "name": null }, { "creator_type": "author", "first_name": "Kazuo", "last_name": "Funabiki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.crmeth.2025.101056" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "40472849" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Cell Proliferation", "descriptor_ui": "D049109", "major_topic": false }, { "descriptor": "Endoscopy", "descriptor_ui": "D004724", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Intravital Microscopy", "descriptor_ui": "D000069416", "major_topic": true }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Nude", "descriptor_ui": "D008819", "major_topic": false }, { "descriptor": "Neoplasms", "descriptor_ui": "D009369", "major_topic": true } ], "publication": { "conference_name": null, "date": "2025 May 28", "date_precision": "day", "issue": "", "normalized_date": "2025-05-28", "pages": "101056", "proceedings_title": null, "publisher": "", "title": "Cell reports methods", "volume": "", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Microendoscopy for periodic intravital end-to-end tumor imaging of cancer cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Surface functionalization of gold nanoparticles (AuNPs) to impart colloidal stability is imperative for their applications, especially in biomedical fields. A drastic dispersion stabilizing effect of defect-free cyclic poly(ethylene glycol) (c-PEG) through their physisorption onto the surface of AuNPs was previously discovered, which was even superior to the de facto standard, thiolated PEG (HS-PEG-OMe). Here, we report a comprehensive characterization of the unique structure of the AuNPs/c-PEG complex using nuclear magnetic resonance (NMR) and small-angle neutron scattering (SANS). Furthermore, molecular dynamics (MD) simulations were employed to elucidate the distinct mechanism of physisorption. Quantification of the adsorbed c-PEG molecules by NMR revealed that the adsorption density (sigma) is approximately 1 order of magnitude smaller than that of HS-PEG-OMe. Model-independent and -dependent analyses of the SANS data were used to further identify the relatively thin and sparse PEG layer as a characteristic of c-PEG adsorption. MD simulations of the physisorption events revealed the absolute value of free energy of adsorption for c-PEG to be greater than that for linear HO-PEG-OH. The favorable adsorption of c-PEG is suggested to arise from its less hydrated state and the larger number of water molecules that are released from the gold surface upon PEG adsorption.", "classifications": [ { "id": "Yamamoto", "label": "Group Yamamoto", "parent": "Toyoshima", "type": "group" }, { "id": "Toyoshima", "label": "Team Toyoshima", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Tomohisa", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Masato", "last_name": "Yamasaki", "name": null }, { "creator_type": "author", "first_name": "Tsuyoshi", "last_name": "Nakai", "name": null }, { "creator_type": "author", "first_name": "Bincy Akkoli", "last_name": "Pottammal", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Maruyama", "name": null }, { "creator_type": "author", "first_name": "Hiroki", "last_name": "Iwase", "name": null }, { "creator_type": "author", "first_name": "Akiyuki", "last_name": "Ryoki", "name": null }, { "creator_type": "author", "first_name": "Tianle", "last_name": "Gao", "name": null }, { "creator_type": "author", "first_name": "Feng", "last_name": "Li", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Isono", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Tajima", "name": null }, { "creator_type": "author", "first_name": "Toshifumi", "last_name": "Satoh", "name": null }, { "creator_type": "author", "first_name": "Shin-Ichiro", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Yamamoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/acs.langmuir.5c00930" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "40420393" } }, "mesh": [], "publication": { "conference_name": null, "date": "2025 May 26", "date_precision": "day", "issue": "", "normalized_date": "2025-05-26", "pages": "", "proceedings_title": null, "publisher": "", "title": "Langmuir : the ACS journal of surfaces and colloids", "volume": "", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Unique Complex Structure and Mechanism of Physisorption of Defect-Free Cyclic Poly(ethylene glycol) onto Gold Nanoparticles.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: Potassium ions (K(+)) are essential for platelet function, yet their role in thrombopoiesis-particularly through specific K(+) channels-remains poorly understood. This gap is especially relevant in the context of in vitro platelet production from induced pluripotent stem cell (iPSC)-derived immortalized megakaryocyte progenitor cell lines (imMKCLs), which we have developed for clinical-grade platelet manufacturing. OBJECTIVE: We aimed to elucidate how K(+) channels contribute to platelet biogenesis, focusing specifically on the calcium ion (Ca(2+))-activated K(+) channel KCNN4 (also known as K(Ca)3.1). METHODS: Using imMKCLs and human cord blood-derived megakaryocytes (CB-megakaryocytes), we analyzed intracellular cation dynamics during platelet production. RNA sequencing profiling was conducted to identify K(+) channel gene expression changes, focusing on KCNN4. Its role in proplatelet formation and platelet release was examined using pharmacological inhibitors and gene knockdown (KD). We further investigated the link between KCNN4 and microtubule organization, mitochondrial function, and reactive oxygen species (ROS) levels. RESULTS: A progressive decline in intracellular K(+) concentration ([K(+)]ᵢ) was observed during the six-day maturation period of imMKCLs. KCNN4 was upregulated at onset of platelet generation, and its inhibition or KD led to impaired proplatelet formation and reduced platelet yield in both imMKCLs and CB-megakaryocytes. These effects were accompanied by decreased [K(+)]ᵢ, reduced mitochondrial membrane potential, and increased ROS accumulation. CONCLUSIONS: Our findings reveal that the KCNN4-mediated reduction in [K(+)]ᵢ is a crucial mechanism linking cytoskeletal reorganization, mitochondrial function, and ROS homeostasis to effective thrombopoiesis. This study provides new insights into platelet biogenesis and offers potential avenues to optimize ex vivo platelet production.", "classifications": [ { "id": "Yamamoto", "label": "Group Yamamoto", "parent": "Toyoshima", "type": "group" }, { "id": "Toyoshima", "label": "Team Toyoshima", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Qihao", "last_name": "Chen", "name": null }, { "creator_type": "author", "first_name": "Sou", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Naoya", "last_name": "Takayama", "name": null }, { "creator_type": "author", "first_name": "Naoshi", "last_name": "Sugimoto", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Eto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.jtha.2025.05.013" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "40412718" } }, "mesh": [ { "descriptor": "Blood Platelets", "descriptor_ui": "D001792", "major_topic": true }, { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Induced Pluripotent Stem Cells", "descriptor_ui": "D057026", "major_topic": false }, { "descriptor": "Intermediate-Conductance Calcium-Activated Potassium Channels", "descriptor_ui": "D051660", "major_topic": true }, { "descriptor": "Megakaryocyte Progenitor Cells", "descriptor_ui": "D055016", "major_topic": true }, { "descriptor": "Megakaryocytes", "descriptor_ui": "D008533", "major_topic": false }, { "descriptor": "Membrane Potential, Mitochondrial", "descriptor_ui": "D053078", "major_topic": false }, { "descriptor": "Microtubules", "descriptor_ui": "D008870", "major_topic": false }, { "descriptor": "Mitochondria", "descriptor_ui": "D008928", "major_topic": true }, { "descriptor": "Potassium", "descriptor_ui": "D011188", "major_topic": true }, { "descriptor": "Reactive Oxygen Species", "descriptor_ui": "D017382", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Thrombopoiesis", "descriptor_ui": "D034061", "major_topic": true } ], "publication": { "conference_name": null, "date": "2025 May 22", "date_precision": "day", "issue": "", "normalized_date": "2025-05-22", "pages": "S1538-7836(25)00331-9", "proceedings_title": null, "publisher": "", "title": "Journal of thrombosis and haemostasis : JTH", "volume": "", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "KCNN4-mediated potassium ion efflux maintains mitochondrial functions leading to platelet biogenesis.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Glycyrrhetinic acid (GA), a triterpenoid saponin from licorice (Glycyrrhiza species) exerts diverse biological activities in animal cells, including anti-inflammatory, antiviral, and antitumor effects. However, the effects of GA on plant cells remain largely unexplored. In this study, we investigated the effects of GA on tobacco BY-2 cells, a plant cell culture system that serves as a useful model for studying cell death in highly proliferative plant cells. Treatment of BY-2 cells with GA resulted in a significant increase in cell death in a manner dependent on both concentration and time. To elucidate the mechanisms underlying GA-induced cell death, we evaluated mitochondrial membrane potential and lipid peroxidation using fluorescent probes. GA treatment caused a marked decrease in mitochondrial membrane potential, along with an increase in lipid peroxidation levels. These findings suggest that GA induces cell death in plant cultured cells, accompanied by mitochondrial dysfunction and lipid peroxidation. Our results provide new insights into the biological activity of GA in plant cells and suggest the involvement of mitochondrial and lipid peroxidation-related pathways in GA-induced cell death.", "classifications": [ { "id": "JPMJCR2121", "label": "JPMJCR2121", "researcher": "Minako Ueda", "type": "grant" }, { "id": "Higaki", "label": "Group Higaki", "parent": "Ueda", "type": "group" }, { "id": "Ueda", "label": "Group Ueda", "parent": "Ueda", "type": "group" }, { "id": "Ueda", "label": "Team Ueda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Kazuma", "last_name": "Hirase", "name": null }, { "creator_type": "author", "first_name": "Takumi", "last_name": "Higaki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.bbrc.2025.152062" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "40412370" } }, "mesh": [ { "descriptor": "Apoptosis", "descriptor_ui": "D017209", "major_topic": true }, { "descriptor": "Cell Death", "descriptor_ui": "D016923", "major_topic": false }, { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "Glycyrrhetinic Acid", "descriptor_ui": "D006034", "major_topic": true }, { "descriptor": "Lipid Peroxidation", "descriptor_ui": "D015227", "major_topic": true }, { "descriptor": "Membrane Potential, Mitochondrial", "descriptor_ui": "D053078", "major_topic": false }, { "descriptor": "Mitochondria", "descriptor_ui": "D008928", "major_topic": false }, { "descriptor": "Nicotiana", "descriptor_ui": "D014026", "major_topic": true } ], "publication": { "conference_name": null, "date": "2025 May 21", "date_precision": "day", "issue": "", "normalized_date": "2025-05-21", "pages": "152062", "proceedings_title": null, "publisher": "", "title": "Biochemical and biophysical research communications", "volume": "772", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Glycyrrhetinic acid triggers lipid peroxidation-related cell death in tobacco BY-2 cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The Nitric Oxide Society and its journal, Nitric Oxide: Biology and Chemistry, are renewing their partnership to reconnect with their founding mission-supporting a dynamic, global redox community. Established together in 1996, the Society and Journal now return to a shared path, aligning efforts to empower young scientists, promote rigorous publishing, and foster open, international collaboration. As nitric oxide and related species move to the forefront of biomedical research and personalized medicine, this relaunch is less a restart than a return to form-focused, inclusive, and forward-looking.", "classifications": [ { "id": "Nishida", "label": "Group Nishida", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Miriam M.", "last_name": "Cortese-Krott", "name": null }, { "creator_type": "author", "first_name": "Lorenzo", "last_name": "Berra", "name": null }, { "creator_type": "author", "first_name": "Nathan S.", "last_name": "Bryan", "name": null }, { "creator_type": "author", "first_name": "Mattias", "last_name": "Carlstrom", "name": null }, { "creator_type": "author", "first_name": "Sharon", "last_name": "Glynn", "name": null }, { "creator_type": "author", "first_name": "Adrian", "last_name": "Hobbs", "name": null }, { "creator_type": "author", "first_name": "Katrina", "last_name": "Miranda", "name": null }, { "creator_type": "author", "first_name": "Hozumi", "last_name": "Motohashi", "name": null }, { "creator_type": "author", "first_name": "Motohiro", "last_name": "Nishida", "name": null }, { "creator_type": "author", "first_name": "Ciara E.", "last_name": "O'Neil", "name": null }, { "creator_type": "author", "first_name": "Jesus", "last_name": "Tejero", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.niox.2025.05.005" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "40409534" } }, "mesh": [ { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Nitric Oxide", "descriptor_ui": "D009569", "major_topic": true }, { "descriptor": "Oxidation-Reduction", "descriptor_ui": "D010084", "major_topic": false }, { "descriptor": "Periodicals as Topic", "descriptor_ui": "D010506", "major_topic": true }, { "descriptor": "Societies, Scientific", "descriptor_ui": "D012958", "major_topic": true } ], "publication": { "conference_name": null, "date": "2025 May 21", "date_precision": "day", "issue": "", "normalized_date": "2025-05-21", "pages": "S1089-8603(25)00045-X", "proceedings_title": null, "publisher": "", "title": "Nitric oxide : biology and chemistry", "volume": "", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "The Nitric oxide Society and the Nitric Oxide Journal: Returning to Our Foundation to Shape the Future of Redox Biology.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: Pathogenic variants (PVs) of BRCA1 and BRCA2 predispose individuals to a higher risk of breast and ovarian cancer; however, the precise risks posed by other cancer susceptibility genes remain unclear, particularly in Asian populations. METHODS: We executed a case-control study of 11 and 26 genes associated with breast and ovarian cancer susceptibility, respectively, in 7220 women with breast cancer, 2464 women with ovarian cancer, and 4032 controls from a multicentre, hospital-based registry in Japan. Furthermore, we conducted a meta-analysis of 23,193 patients with breast and/or ovarian cancer and 31,190 controls from six other hospital-based studies. FINDINGS: Overall, 395 (5.5%) patients with breast cancer and 331 (13.4%) patients with ovarian cancer harboured PVs. Meta-analyses revealed that PVs of BRCA1, BRCA2, CHEK2, PALB2, and TP53 were associated significantly with breast cancer risk (P < 0.001), while PVs of ATM, BRCA1, BRCA2, MSH6, and RAD51D were associated significantly with ovarian cancer risk (P < 0.001). PVs in the BRCA1 DNA-binding domain were associated with a younger age at diagnosis after adjusting for cancer type and family history (beta = -3.79, 95% CI = -7.16 to -0.41; P = 0.028). INTERPRETATION: These results provide information about genes associated with breast and ovarian cancer risk in Asian women, as well as guidance for management of PV carriers. FUNDING: The study was funded by AMED (JP15ck010609, 19cm0106605h0003, 23ama221520h0001, and JP19kk0305010), by a Health Labour Sciences Research Grant (202108001B), by JSPS KAKENHI (JP18K16292, 20H03668, 23H02955, 17H06162, 20H03695, and 16H06277), and by a Grant-in-Aid for the Genome Research Project from Yamanashi Prefecture.", "classifications": [ { "id": "Hamamoto", "label": "Group Hamamoto", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Shu", "last_name": "Yazaki", "name": null }, { "creator_type": "author", "first_name": "Megumi", "last_name": "Hori", "name": null }, { "creator_type": "author", "first_name": "Hisaki", "last_name": "Aiba", "name": null }, { "creator_type": "author", "first_name": "Yukihide", "last_name": "Momozawa", "name": null }, { "creator_type": "author", "first_name": "Masayuki", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Sho", "last_name": "Shiino", "name": null }, { "creator_type": "author", "first_name": "Kenichi", "last_name": "Harano", "name": null }, { "creator_type": "author", "first_name": "Chisako", "last_name": "Yamauchi", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Yamanaka", "name": null }, { "creator_type": "author", "first_name": "Maiko", "last_name": "Miwa", "name": null }, { "creator_type": "author", "first_name": "Koichi", "last_name": "Matsuda", "name": null }, { "creator_type": "author", "first_name": "Yosuke", "last_name": "Kawai", "name": null }, { "creator_type": "author", "first_name": "Mayumi", "last_name": "Kobayashi-Kato", "name": null }, { "creator_type": "author", "first_name": "Masakazu", "last_name": "Kitagawa", "name": null }, { "creator_type": "author", "first_name": "Motonobu", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Nakagomi", "name": null }, { "creator_type": "author", "first_name": "Kazunoshin", "last_name": "Tachibana", "name": null }, { "creator_type": "author", "first_name": "Ikuko", "last_name": "Sakamoto", "name": null }, { "creator_type": "author", "first_name": "Kazuaki", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Yuka", "last_name": "Asami", "name": null }, { "creator_type": "author", "first_name": "Kota", "last_name": "Katanoda", "name": null }, { "creator_type": "author", "first_name": "Aya", "last_name": "Kuchiba", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Mitsuya", "last_name": "Ishikawa", "name": null }, { "creator_type": "author", "first_name": "Tastunori", "last_name": "Shimoi", "name": null }, { "creator_type": "author", "first_name": "Kazuki", "last_name": "Sudo", "name": null }, { "creator_type": "author", "first_name": "Chikako", "last_name": "Shimizu", "name": null }, { "creator_type": "author", "first_name": "Akihiko", "last_name": "Shimomura", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Murata", "name": null }, { "creator_type": "author", "first_name": "Yuji", "last_name": "Yamashita", "name": null }, { "creator_type": "author", "first_name": "Takahiro", "last_name": "Kogawa", "name": null }, { "creator_type": "author", "first_name": "Saori", "last_name": "Fujiwara", "name": null }, { "creator_type": "author", "first_name": "Haruya", "last_name": "Saji", "name": null }, { "creator_type": "author", "first_name": "Hisamori", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Etsuko", "last_name": "Miyagi", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Iwasaki", "name": null }, { "creator_type": "author", "first_name": "Tomomi", "last_name": "Aoi", "name": null }, { "creator_type": "author", "first_name": "Sadaaki", "last_name": "Takata", "name": null }, { "creator_type": "author", "first_name": "Aiko", "last_name": "Ogasawara", "name": null }, { "creator_type": "author", "first_name": "Tohru", "last_name": "Ohtake", "name": null }, { "creator_type": "author", "first_name": "Keiya", "last_name": "Fujimori", "name": null }, { "creator_type": "author", "first_name": "Yosuke", "last_name": "Hirotsu", "name": null }, { "creator_type": "author", "first_name": "Minoru", "last_name": "Nagashima", "name": null }, { "creator_type": "author", "first_name": "Masaaki", "last_name": "Komatsu", "name": null }, { "creator_type": "author", "first_name": "Ryuji", "last_name": "Hamamoto", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Hirata", "name": null }, { "creator_type": "author", "first_name": "Teruhiko", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Takayuki", "last_name": "Honda", "name": null }, { "creator_type": "author", "first_name": "Kengo", "last_name": "Hiranuma", "name": null }, { "creator_type": "author", "first_name": "Maiko", "last_name": "Matsuda", "name": null }, { "creator_type": "author", "first_name": "Yoko", "last_name": "Shimada", "name": null }, { "creator_type": "author", "first_name": "Kuniko", "last_name": "Sunami", "name": null }, { "creator_type": "author", "first_name": "Eisei", "last_name": "Noiri", "name": null }, { "creator_type": "author", "first_name": "Yosuke", "last_name": "Omae", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Matsumoto", "name": null }, { "creator_type": "author", "first_name": "Aikou", "last_name": "Okamoto", "name": null }, { "creator_type": "author", "first_name": "Masao", "last_name": "Omata", "name": null }, { "creator_type": "author", "first_name": "Takafumi", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Yohei", "last_name": "Miyagi", "name": null }, { "creator_type": "author", "first_name": "Yoshinori", "last_name": "Murakami", "name": null }, { "creator_type": "author", "first_name": "Katsushi", "last_name": "Tokunaga", "name": null }, { "creator_type": "author", "first_name": "Kosei", "last_name": "Hasegawa", "name": null }, { "creator_type": "author", "first_name": "Tomoyasu", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Onishi", "name": null }, { "creator_type": "author", "first_name": "Toshinari", "last_name": "Yamashita", "name": null }, { "creator_type": "author", "first_name": "Yoichi", "last_name": "Naito", "name": null }, { "creator_type": "author", "first_name": "Akihiko", "last_name": "Suto", "name": null }, { "creator_type": "author", "first_name": "Kan", "last_name": "Yonemori", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Kohno", "name": null }, { "creator_type": "author", "first_name": "Kouya", "last_name": "Shiraisihi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.ebiom.2025.105758" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "40403695" } }, "mesh": [ { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "BRCA1 Protein", "descriptor_ui": "D019313", "major_topic": false }, { "descriptor": "BRCA2 Protein", "descriptor_ui": "D024682", "major_topic": false }, { "descriptor": "Breast Neoplasms", "descriptor_ui": "D001943", "major_topic": true }, { "descriptor": "Case-Control Studies", "descriptor_ui": "D016022", "major_topic": false }, { "descriptor": "East Asian People", "descriptor_ui": "D000095225", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Genetic Predisposition to Disease", "descriptor_ui": "D020022", "major_topic": true }, { "descriptor": "Germ-Line Mutation", "descriptor_ui": "D018095", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Japan", "descriptor_ui": "D007564", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Ovarian Neoplasms", "descriptor_ui": "D010051", "major_topic": true }, { "descriptor": "Risk Factors", "descriptor_ui": "D012307", "major_topic": false } ], "publication": { "conference_name": null, "date": "2025 May 21", "date_precision": "day", "issue": "", "normalized_date": "2025-05-21", "pages": "105758", "proceedings_title": null, "publisher": "", "title": "EBioMedicine", "volume": "116", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Impact of germline variants on breast and ovarian cancer risk in Japanese women: an original cohort study and meta-analysis.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Cell-tagging strategies with DNA barcodes have enabled the analysis of clone size dynamics and clone-restricted transcriptomic landscapes in heterogeneous populations. However, isolating a target clone that displays a specific phenotype from a complex population remains challenging. Here we present a multi-kingdom genetic barcoding system, CloneSelect, which enables a target cell clone to be triggered to express a reporter gene for isolation through barcode-specific CRISPR base editing. In CloneSelect, cells are first stably tagged with DNA barcodes and propagated so that their subpopulation can be subjected to a given experiment. A clone that shows a phenotype or genotype of interest at a given time can then be isolated from the initial or subsequent cell pools stored during the experiment using CRISPR base editing. CloneSelect is scalable and compatible with single-cell RNA sequencing. We demonstrate the versatility of CloneSelect in human embryonic kidney 293T cells, mouse embryonic stem cells, human pluripotent stem cells, yeast cells and bacterial cells.", "classifications": [ { "id": "Yamamoto", "label": "Group Yamamoto", "parent": "Toyoshima", "type": "group" }, { "id": "Toyoshima", "label": "Team Toyoshima", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Soh", "last_name": "Ishiguro", "name": null }, { "creator_type": "author", "first_name": "Kana", "last_name": "Ishida", "name": null }, { "creator_type": "author", "first_name": "Rina C.", "last_name": "Sakata", "name": null }, { "creator_type": "author", "first_name": "Minori", "last_name": "Ichiraku", "name": null }, { "creator_type": "author", "first_name": "Ren", "last_name": "Takimoto", "name": null }, { "creator_type": "author", "first_name": "Rina", "last_name": "Yogo", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Kijima", "name": null }, { "creator_type": "author", "first_name": "Hideto", "last_name": "Mori", "name": null }, { "creator_type": "author", "first_name": "Mamoru", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Samuel", "last_name": "King", "name": null }, { "creator_type": "author", "first_name": "Shoko", "last_name": "Tarumoto", "name": null }, { "creator_type": "author", "first_name": "Taro", "last_name": "Tsujimura", "name": null }, { "creator_type": "author", "first_name": "Omar", "last_name": "Bashth", "name": null }, { "creator_type": "author", "first_name": "Nanami", "last_name": "Masuyama", "name": null }, { "creator_type": "author", "first_name": "Arman", "last_name": "Adel", "name": null }, { "creator_type": "author", "first_name": "Hiromi", "last_name": "Toyoshima", "name": null }, { "creator_type": "author", "first_name": "Motoaki", "last_name": "Seki", "name": null }, { "creator_type": "author", "first_name": "Ju Hee", "last_name": "Oh", "name": null }, { "creator_type": "author", "first_name": "Anne-Sophie", "last_name": "Archambault", "name": null }, { "creator_type": "author", "first_name": "Keiji", "last_name": "Nishida", "name": null }, { "creator_type": "author", "first_name": "Akihiko", "last_name": "Kondo", "name": null }, { "creator_type": "author", "first_name": "Satoru", "last_name": "Kuhara", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Aburatani", "name": null }, { "creator_type": "author", "first_name": "Ramon I.", "last_name": "Klein Geltink", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Nika", "last_name": "Shakiba", "name": null }, { "creator_type": "author", "first_name": "Yasuhiro", "last_name": "Takashima", "name": null }, { "creator_type": "author", "first_name": "Nozomu", "last_name": "Yachie", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41587-025-02649-1" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "40399693" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Clone Cells", "descriptor_ui": "D002999", "major_topic": false }, { "descriptor": "CRISPR-Cas Systems", "descriptor_ui": "D064113", "major_topic": false }, { "descriptor": "DNA Barcoding, Taxonomic", "descriptor_ui": "D058893", "major_topic": true }, { "descriptor": "Gene Editing", "descriptor_ui": "D000072669", "major_topic": false }, { "descriptor": "Genes, Reporter", "descriptor_ui": "D017930", "major_topic": false }, { "descriptor": "HEK293 Cells", "descriptor_ui": "D057809", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Single-Cell Analysis", "descriptor_ui": "D059010", "major_topic": false } ], "publication": { "conference_name": null, "date": "2025 May 21", "date_precision": "day", "issue": "", "normalized_date": "2025-05-21", "pages": "", "proceedings_title": null, "publisher": "", "title": "Nature biotechnology", "volume": "", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "A multi-kingdom genetic barcoding system for precise clone isolation.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Oxygen and sulfur, both members of the chalcogen group (group 16 elements), play fundamental roles in life. Ancient organisms primarily utilized sulfur for energy metabolism, while the rise in atmospheric oxygen facilitated the evolution of aerobic organisms, enabling highly efficient energy production. Nevertheless, all modern organisms, both aerobes and anaerobes, must protect themselves from oxygen toxicity. Interestingly, aerobes still rely on sulfur for survival. This dependence has been illuminated by the recent discovery of supersulfides, a novel class of biomolecules, made possible through advancements in technology and analytical methods. These breakthroughs are reshaping our understanding of biological processes and emphasizing the intricate interplay between oxygen and sulfur in regulating essential redox reactions. This review summarizes the latest insights into the biological roles of sulfur and oxygen, their interdependence in key processes, and their contributions to adaptive responses to environmental stressors. By exploring these interactions, we aim to provide a comprehensive perspective on how these elements drive survival strategies across diverse life forms, highlighting their indispensable roles in both human health and the sustenance of life.", "classifications": [ { "id": "JPMJCR2024", "label": "JPMJCR2024", "researcher": "Motohiro Nishida", "type": "grant" }, { "id": "Akaike", "label": "Group Akaike", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Group Nishida", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Hiroki", "last_name": "Sekine", "name": null }, { "creator_type": "author", "first_name": "Takaaki", "last_name": "Akaike", "name": null }, { "creator_type": "author", "first_name": "Hozumi", "last_name": "Motohashi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s44318-025-00464-7" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "40394395" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Bacteria", "descriptor_ui": "D001419", "major_topic": false }, { "descriptor": "Energy Metabolism", "descriptor_ui": "D004734", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Oxidation-Reduction", "descriptor_ui": "D010084", "major_topic": false }, { "descriptor": "Oxygen", "descriptor_ui": "D010100", "major_topic": true }, { "descriptor": "Sulfur", "descriptor_ui": "D013455", "major_topic": true } ], "publication": { "conference_name": null, "date": "2025 May 20", "date_precision": "day", "issue": "", "normalized_date": "2025-05-20", "pages": "", "proceedings_title": null, "publisher": "", "title": "The EMBO journal", "volume": "", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Oxygen needs sulfur, sulfur needs oxygen: a relationship of interdependence.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The Japanese government's recent lowering of the legal adult age to 18 may prompt reconsideration of the minimum age for donors in the Japan Marrow Donor Program. To provide foundational data for decision-makers, this retrospective study analyzed the safety of hematopoietic stem cell donation among 1999 related donors aged 18 to 24 years, using data from the Japanese Data Center for Hematopoietic Cell Transplantation. Severe adverse events (SAEs) occurred in 1.0% of all donors, with no significant difference between those aged 18 to 19 (0.7%) and those aged 20 to 24 (1.1%) (P = 0.59). Risk factors for SAEs included ongoing asthma treatment (HR 34.6, 95% CI 2.29-524.00, P < 0.01), history of asthma (HR 11.3, 95% CI 2.46-51.70, P < 0.01), and female sex (HR 4.64, 95% CI 1.51-14.20, P < 0.01). However, age of 18 to 19 was not a significant risk factor (HR 0.53, 95% CI 0.14-2.01, P = 0.35). These results indicate that stem cell donation safety in 18- to 19-year-old donors is comparable to that in 20- to 24-year-olds, with increased risks linked to asthma and female sex.", "classifications": [ { "id": "Nishikii", "label": "Group Nishikii", "parent": "Shintaku", "type": "group" }, { "id": "Shintaku", "label": "Team Shintaku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Tsuneaki", "last_name": "Hirakawa", "name": null }, { "creator_type": "author", "first_name": "Hiromasa", "last_name": "Yabe", "name": null }, { "creator_type": "author", "first_name": "Masayuki", "last_name": "Hino", "name": null }, { "creator_type": "author", "first_name": "Noriko", "last_name": "Doki", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Yoshihara", "name": null }, { "creator_type": "author", "first_name": "Shuichi", "last_name": "Ota", "name": null }, { "creator_type": "author", "first_name": "Takahiro", "last_name": "Fukuda", "name": null }, { "creator_type": "author", "first_name": "Hirohisa", "last_name": "Nakamae", "name": null }, { "creator_type": "author", "first_name": "Jun", "last_name": "Ishikawa", "name": null }, { "creator_type": "author", "first_name": "Yuta", "last_name": "Hasegawa", "name": null }, { "creator_type": "author", "first_name": "Tetsuya", "last_name": "Nishida", "name": null }, { "creator_type": "author", "first_name": "Noboru", "last_name": "Asada", "name": null }, { "creator_type": "author", "first_name": "Hidekazu", "last_name": "Nishikii", "name": null }, { "creator_type": "author", "first_name": "Toshiro", "last_name": "Kawakita", "name": null }, { "creator_type": "author", "first_name": "Masayoshi", "last_name": "Masuko", "name": null }, { "creator_type": "author", "first_name": "Yasuo", "last_name": "Mori", "name": null }, { "creator_type": "author", "first_name": "Toshihiko", "last_name": "Ando", "name": null }, { "creator_type": "author", "first_name": "Kazuhiko", "last_name": "Ikeda", "name": null }, { "creator_type": "author", "first_name": "Marie", "last_name": "Ohbiki", "name": null }, { "creator_type": "author", "first_name": "Yoshiko", "last_name": "Atsuta", "name": null }, { "creator_type": "author", "first_name": "Nobuhiro", "last_name": "Tsukada", "name": null }, { "creator_type": "author", "first_name": "Ryu", "last_name": "Yanagisawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/s12185-025-04007-y" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "40392464" } }, "mesh": [ { "descriptor": "Adolescent", "descriptor_ui": "D000293", "major_topic": false }, { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Age Factors", "descriptor_ui": "D000367", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Hematopoietic Stem Cell Transplantation", "descriptor_ui": "D018380", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Japan", "descriptor_ui": "D007564", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Retrospective Studies", "descriptor_ui": "D012189", "major_topic": false }, { "descriptor": "Risk Factors", "descriptor_ui": "D012307", "major_topic": false }, { "descriptor": "Tissue Donors", "descriptor_ui": "D014019", "major_topic": true }, { "descriptor": "Young Adult", "descriptor_ui": "D055815", "major_topic": false } ], "publication": { "conference_name": null, "date": "2025 May 20", "date_precision": "day", "issue": "", "normalized_date": "2025-05-20", "pages": "", "proceedings_title": null, "publisher": "", "title": "International journal of hematology", "volume": "", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Safety of hematopoietic stem cell donation from young related donors following the lowering of the age of legal adulthood in Japan.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Enhancers are non-coding DNA regions that facilitate gene transcription, with a specialized subset, super-enhancers, known to exert exceptionally strong transcriptional activation effects. Super-enhancers have been implicated in oncogenesis, and their identification is achievable through histone mark chromatin immunoprecipitation followed by sequencing data using existing analytical tools. However, conventional super-enhancer detection methodologies often do not accurately reflect actual gene expression levels, and the large volume of identified super-enhancers complicates comprehensive analysis. To address these limitations, we developed the super-enhancer to gene links (SE-to-gene Links) analysis, a platform named \"SEgene\" which incorporates the peak-to-gene links approach-a statistical method designed to reveal correlations between genes and peak regions ( https://github.com/hamamoto-lab/SEgene ). This platform enables a targeted evaluation of super-enhancer regions in relation to gene expression, facilitating the identification of super-enhancers that are functionally linked to transcriptional activity. Here, we demonstrate the application of SE-to-gene Links analysis to public datasets, confirming its efficacy in accurately detecting super-enhancers and identifying functionally associated genes. Additionally, SE-to-gene Links analysis identified ERBB2 as a significant gene of interest in the lung adenocarcinoma dataset from the National Cancer Center Japan cohort, suggesting a potential impact across multiple patient samples. Thus, the SE-to-gene Links analysis provides an analytical tool for evaluating super-enhancers as potential therapeutic targets, supporting the identification of clinically significant super-enhancer regions and their functionally associated genes.", "classifications": [ { "id": "Hamamoto", "label": "Group Hamamoto", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Norio", "last_name": "Shinkai", "name": null }, { "creator_type": "author", "first_name": "Ken", "last_name": "Asada", "name": null }, { "creator_type": "author", "first_name": "Hidenori", "last_name": "Machino", "name": null }, { "creator_type": "author", "first_name": "Ken", "last_name": "Takasawa", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Nobuji", "last_name": "Kouno", "name": null }, { "creator_type": "author", "first_name": "Masaaki", "last_name": "Komatsu", "name": null }, { "creator_type": "author", "first_name": "Ryuji", "last_name": "Hamamoto", "name": null }, { "creator_type": "author", "first_name": "Syuzo", "last_name": "Kaneko", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41540-025-00533-x" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "40389443" } }, "mesh": [ { "descriptor": "Adenocarcinoma of Lung", "descriptor_ui": "D000077192", "major_topic": false }, { "descriptor": "Computational Biology", "descriptor_ui": "D019295", "major_topic": true }, { "descriptor": "Enhancer Elements, Genetic", "descriptor_ui": "D004742", "major_topic": true }, { "descriptor": "Gene Expression", "descriptor_ui": "D015870", "major_topic": true }, { "descriptor": "Gene Expression Regulation, Neoplastic", "descriptor_ui": "D015972", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Lung Neoplasms", "descriptor_ui": "D008175", "major_topic": false }, { "descriptor": "Super Enhancers", "descriptor_ui": "D000095483", "major_topic": false } ], "publication": { "conference_name": null, "date": "2025 May 19", "date_precision": "day", "issue": "1", "normalized_date": "2025-05-19", "pages": "49", "proceedings_title": null, "publisher": "", "title": "NPJ systems biology and applications", "volume": "11", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "SEgene identifies links between super enhancers and gene expression across cell types.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Several classifications have been proposed to define rare cancers; however, the pathophysiological understanding of tumors evolves rapidly. We propose a New Classification of Rare Cancer (NCRC) using the updated International Classification of Diseases for Oncology 3.2 coding system and World Health Organization Classification of Tumors 5th edition. We applied patient data recorded in the National Cancer Registry of Japan to the new classification, setting a cut-off of a crude incidence rate of 6 cases/100 000/year to define rare cancers, and developed a list of rare cancers in Japan from 2016 to 2019. The NCRC system identified various rare cancers, comprising 20.0% of all cancer diagnoses in this period. To examine this classification system's performance, we compared rare/non-rare labeling of cancers by the Surveillance of Rare Cancers in Europe (RARECARENet) project and NCRC system. Compared with cases using the RARECARENet classification in Europe, 69 351 cases/year (6.8%) switched status with our classification, with 45 293 and 232 109 cases (4 years) switching from rare and non-rare, respectively. Major differences included diffuse large B-cell lymphomas, some thyroid cancers, oral cavity and lip cancers, and squamous cell carcinoma of the uterine cervix. As the NCRC includes newly classified tumor entities, it warrants validation using other diverse cohorts.", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Ryoko", "last_name": "Rikitake", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null }, { "creator_type": "author", "first_name": "Yoko", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Tatsunori", "last_name": "Shimoi", "name": null }, { "creator_type": "author", "first_name": "Shintaro", "last_name": "Iwata", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Goto", "name": null }, { "creator_type": "author", "first_name": "Yu", "last_name": "Mizushima", "name": null }, { "creator_type": "author", "first_name": "Akira", "last_name": "Kawai", "name": null }, { "creator_type": "author", "first_name": "Takahiro", "last_name": "Higashi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/pin.70021" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "40376725" } }, "mesh": [ { "descriptor": "Europe", "descriptor_ui": "D005060", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Incidence", "descriptor_ui": "D015994", "major_topic": false }, { "descriptor": "International Classification of Diseases", "descriptor_ui": "D038801", "major_topic": false }, { "descriptor": "Japan", "descriptor_ui": "D007564", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Neoplasms", "descriptor_ui": "D009369", "major_topic": true }, { "descriptor": "Rare Diseases", "descriptor_ui": "D035583", "major_topic": true }, { "descriptor": "Registries", "descriptor_ui": "D012042", "major_topic": false } ], "publication": { "conference_name": null, "date": "2025 May 16", "date_precision": "day", "issue": "", "normalized_date": "2025-05-16", "pages": "", "proceedings_title": null, "publisher": "", "title": "Pathology international", "volume": "", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Proposal for a New Classification of Rare Cancers Adopting Updated Histological Tumor Types.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "alpha,alpha-Disubstituted alpha-amino acids such as alpha-aminoisobutyric acid (Aib), in their polymeric structures, are known to form a 3(10)-helical conformation rather than an alpha-helical conformation, which is usually adopted by polymeric alpha-monosubstituted alpha-amino acids. Even alpha-helically folded Aib oligomers are unprecedented, although they have been predicted by theoretical calculations. In the present paper, we report the first alpha-helically folded Aib oligomer found in the course of our study on the construction of a metal-peptide framework, (Aib)MOF-1. This MOF was synthesized by Zn(2+)-mediated complexation of a pyridyl-functionalized Aib hexamer, Py-Aib(6)-Py, and 5-nitroisophthalate (nip(2-)). Single crystal X-ray diffraction of (Aib)MOF-1 ([Zn(nip)(Py-Aib(6)-Py)](n)) revealed that Py-Aib(6)-Py in (Aib)MOF-1 carried a C horizontal lineO(i) --> NH(i+4) hydrogen bonding array characteristic of alpha-helices, which is distinct from Py-Aib(6)-Py alone adopting a 3(10)-helical conformation with a C horizontal lineO(i) --> NH(i+3) hydrogen bonding array. The alpha-helical Py-Aib(6)-Py units in (Aib)MOF-1 assembled into a superhelical nanotubular architecture with a porous framework. When just the nitro group of the coligand nip(2-) was changed to a tert-butyl group, an MOF ((Aib)MOF-2) with a completely different structure formed, where the constituent Py-Aib(6)-Py units adopted only the 3(10)-helical conformation, just like Py-Aib(6)-Py in its crystalline structure.", "classifications": [ { "id": "Hijikata", "label": "Group Hijikata", "parent": "Tsuchiya", "type": "group" }, { "id": "Tsuchiya", "label": "Team Tsuchiya", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Wei", "last_name": "Yuan", "name": null }, { "creator_type": "author", "first_name": "Jenny", "last_name": "Pirillo", "name": null }, { "creator_type": "author", "first_name": "Yuh", "last_name": "Hijikata", "name": null }, { "creator_type": "author", "first_name": "Takuzo", "last_name": "Aida", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Sato", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/jacs.5c03534" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "40372256" } }, "mesh": [], "publication": { "conference_name": null, "date": "2025 May 15", "date_precision": "day", "issue": "", "normalized_date": "2025-05-15", "pages": "", "proceedings_title": null, "publisher": "", "title": "Journal of the American Chemical Society", "volume": "", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "An alpha-Helically Folded alpha-Aminoisobutyric Acid (Aib) Oligomer That Assembles into a Metal-Peptide Superhelical Nanotube.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND/OBJECTIVE: Ulcerative colitis (UC) is significantly linked with gut microbiota, which is essential for maintaining gut health. Their metabolites mitigate gut inflammation and bolster barrier function. Among these metabolites, we focused on vitamin B3, which has been reported to improve the pathogenesis of UC in mice. This study aimed to compare fecal vitamin B3 and gut microbiota between non-UC and UC patients. METHODS: We assessed fecal metabolites and gut microbiota in 71 UC patients (UC group) and 72 non-UC patients (non-UC group) matched by sex and age in 10-year intervals. Fecal samples were collected and metabolites were analyzed using capillary electrophoresis time-of-flight mass spectrometry. Bacterial DNA was extracted for 16S rRNA gene sequencing. We analyzed fecal nicotinamide levels and gut microbiota composition, employing statistical adjustments for confounding factors. RESULTS: We found that the UC group exhibited significantly lower fecal nicotinamide levels and alpha-diversity (Shannon index) compared to the non-UC group. The relative abundance of bacterial genera such as Treponema, UCG-002, and Fusicatenibacter was decreased, while Sellimonas, Fournierella, and Oscillospira were increased in the UC group. Moreover, a negative correlation was observed between Sellimonas abundance and fecal nicotinamide levels in the UC group. Additionally, the UC group showed higher expression of a bacterial gene encoding nicotinamidase compared to the non-UC group. CONCLUSIONS: These findings suggest that gut microbiota dysbiosis contributes to reduced vitamin B3 metabolism in UC patients. The study highlights the potential of replenishing vitamin B3 metabolic pathways as a novel therapeutic approach for UC treatment.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Keiya", "last_name": "Aoyama", "name": null }, { "creator_type": "author", "first_name": "Ryodai", "last_name": "Yamamura", "name": null }, { "creator_type": "author", "first_name": "Takehiko", "last_name": "Katsurada", "name": null }, { "creator_type": "author", "first_name": "Tomohiro", "last_name": "Shimizu", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Eiji", "last_name": "Kondo", "name": null }, { "creator_type": "author", "first_name": "Norimasa", "last_name": "Iwasaki", "name": null }, { "creator_type": "author", "first_name": "Akiko", "last_name": "Tamakoshi", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Shinji", "last_name": "Fukuda", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Sonoshita", "name": null }, { "creator_type": "author", "first_name": "Naoya", "last_name": "Sakamoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1093/ibd/izaf092" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "40357746" } }, "mesh": [ { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Bacteria", "descriptor_ui": "D001419", "major_topic": true }, { "descriptor": "Case-Control Studies", "descriptor_ui": "D016022", "major_topic": false }, { "descriptor": "Colitis, Ulcerative", "descriptor_ui": "D003093", "major_topic": true }, { "descriptor": "Feces", "descriptor_ui": "D005243", "major_topic": true }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Gastrointestinal Microbiome", "descriptor_ui": "D000069196", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Niacinamide", "descriptor_ui": "D009536", "major_topic": true }, { "descriptor": "RNA, Ribosomal, 16S", "descriptor_ui": "D012336", "major_topic": false }, { "descriptor": "Young Adult", "descriptor_ui": "D055815", "major_topic": false } ], "publication": { "conference_name": null, "date": "2025 May 13", "date_precision": "day", "issue": "", "normalized_date": "2025-05-13", "pages": "izaf092", "proceedings_title": null, "publisher": "", "title": "Inflammatory bowel diseases", "volume": "", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Decreased Fecal Nicotinamide and Increased Bacterial Nicotinamidase Gene Expression in Ulcerative Colitis Patients.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Bacterial persistence is a phenomenon in which a small fraction of isogenic bacterial cells survives a lethal dose of antibiotics. Although the refractoriness of persistent cell populations has classically been attributed to growth-inactive cells generated before drug exposure, evidence is accumulating that actively growing cell fractions can also generate persister cells. However, single-cell characterization of persister cell history remains limited due to the extremely low frequencies of persisters. Here, we visualize the responses of over one million individual cells of wildtype Escherichia coli to lethal doses of antibiotics, sampling cells from different growth phases and culture media into a microfluidic device. We show that when cells sampled from exponentially growing populations were treated with ampicillin or ciprofloxacin, most persisters were growing before antibiotic treatment. Growing persisters exhibited heterogeneous survival dynamics, including continuous growth and fission with L-form-like morphologies, responsive growth arrest, or post-exposure filamentation. Incubating cells under stationary phase conditions increased both the frequency and the probability of survival of non-growing cells to ampicillin. Under ciprofloxacin, however, all persisters identified were growing before the antibiotic treatment, including samples from post-stationary phase culture. These results reveal diverse persister cell dynamics that depend on antibiotic types and pre-exposure history.", "classifications": [ { "id": "JPMJCR1927", "label": "JPMJCR1927", "researcher": "Yuichi Wakamoto", "type": "grant" }, { "id": "Wakamoto", "label": "Group Wakamoto", "parent": "Wakamoto", "type": "group" }, { "id": "Wakamoto", "label": "Team Wakamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Miki", "last_name": "Umetani", "name": null }, { "creator_type": "author", "first_name": "Miho", "last_name": "Fujisawa", "name": null }, { "creator_type": "author", "first_name": "Reiko", "last_name": "Okura", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Nozoe", "name": null }, { "creator_type": "author", "first_name": "Shoichi", "last_name": "Suenaga", "name": null }, { "creator_type": "author", "first_name": "Hidenori", "last_name": "Nakaoka", "name": null }, { "creator_type": "author", "first_name": "Edo", "last_name": "Kussell", "name": null }, { "creator_type": "author", "first_name": "Yuichi", "last_name": "Wakamoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.7554/elife.79517" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "40356339" } }, "mesh": [ { "descriptor": "Ampicillin", "descriptor_ui": "D000667", "major_topic": false }, { "descriptor": "Anti-Bacterial Agents", "descriptor_ui": "D000900", "major_topic": true }, { "descriptor": "Ciprofloxacin", "descriptor_ui": "D002939", "major_topic": false }, { "descriptor": "Drug Resistance, Bacterial", "descriptor_ui": "D024881", "major_topic": true }, { "descriptor": "Escherichia coli", "descriptor_ui": "D004926", "major_topic": true }, { "descriptor": "Microbial Sensitivity Tests", "descriptor_ui": "D008826", "major_topic": false }, { "descriptor": "Microbial Viability", "descriptor_ui": "D050296", "major_topic": true }, { "descriptor": "Single-Cell Analysis", "descriptor_ui": "D059010", "major_topic": false } ], "publication": { "conference_name": null, "date": "2025 May 13", "date_precision": "day", "issue": "", "normalized_date": "2025-05-13", "pages": "e79517", "proceedings_title": null, "publisher": "", "title": "eLife", "volume": "14", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Observation of persister cell histories reveals diverse modes of survival in antibiotic persistence.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Using deep learning-based image restoration, we achieved high-resolution 4D imaging with minimal photodamage, revealing distinct localization and suggesting Lifeact-RFP-labeled actin microfilaments play a role in initiating cell plate formation. Phragmoplasts are plant-specific intracellular structures composed of microtubules, actin microfilaments (AFs), membranes, and associated proteins. Importantly, they are involved in the formation and the expansion of cell plates that partition daughter cells during cell division. While previous studies have revealed the important role of cytoskeletal dynamics in the proper functioning of the phragmoplast, the localization and the role of AFs in the initial phase of cell plate formation remain controversial. Here, we used deep learning-based image restoration to achieve high-resolution 4D imaging with minimal laser-induced damage, enabling us to investigate the dynamics of AFs during the initial phase of cell plate formation in transgenic tobacco BY-2 cells labeled with Lifeact-RFP or RFP-ABD2 (actin-binding domain 2). This computational approach overcame the limitation of conventional imaging, namely laser-induced photobleaching and phototoxicity. The restored images indicated that RFP-ABD2-labeled AFs were predominantly localized near the daughter nucleus, whereas Lifeact-RFP-labeled AFs were found not only near the daughter nucleus but also around the initial cell plate. These findings, validated by imaging with a long exposure time, highlight distinct localization patterns between the two AF probes and suggest that Lifeact-RFP-labeled AFs play a role in initiating cell plate formation.", "classifications": [ { "id": "JPMJCR2121", "label": "JPMJCR2121", "researcher": "Minako Ueda", "type": "grant" }, { "id": "Higaki", "label": "Group Higaki", "parent": "Ueda", "type": "group" }, { "id": "Ueda", "label": "Group Ueda", "parent": "Ueda", "type": "group" }, { "id": "Ueda", "label": "Team Ueda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Suzuka", "last_name": "Kikuchi", "name": null }, { "creator_type": "author", "first_name": "Takumi", "last_name": "Kotaka", "name": null }, { "creator_type": "author", "first_name": "Yuga", "last_name": "Hanaki", "name": null }, { "creator_type": "author", "first_name": "Minako", "last_name": "Ueda", "name": null }, { "creator_type": "author", "first_name": "Takumi", "last_name": "Higaki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/s00299-025-03498-7" }, "pmcid": { "normalized": "PMC12058911" }, "pmid": { "normalized": "40335746" } }, "mesh": [ { "descriptor": "Actin Cytoskeleton", "descriptor_ui": "D008841", "major_topic": true }, { "descriptor": "Actins", "descriptor_ui": "D000199", "major_topic": true }, { "descriptor": "Deep Learning", "descriptor_ui": "D000077321", "major_topic": true }, { "descriptor": "Image Processing, Computer-Assisted", "descriptor_ui": "D007091", "major_topic": true }, { "descriptor": "Nicotiana", "descriptor_ui": "D014026", "major_topic": true }, { "descriptor": "Plants, Genetically Modified", "descriptor_ui": "D030821", "major_topic": false } ], "publication": { "conference_name": null, "date": "2025 May 8", "date_precision": "day", "issue": "6", "normalized_date": "2025-05-08", "pages": "115", "proceedings_title": null, "publisher": "", "title": "Plant cell reports", "volume": "44", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Distinct actin microfilament localization during early cell plate formation through deep learning-based image restoration.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Our method can simultaneously quantify cell wall elasticity and turgor pressure of live plant cells through AFM measurements and calculations based on elastic shell theory. The morphological behavior of plant cells depends on their mechanical properties. Cell wall elasticity (E) and turgor pressure (P) are main factors that dominate the behavior. A method to simultaneously quantify them in live cells has yet to be established, hindering progress in plant mechanobiology. Recently, atomic force microscopy (AFM) has been used to analyze single cells based on Hertz's contact theory (HCT). However, HCT cannot evaluate P. Several groups have attempted to evaluate P by adapting elastic shell theory (EST), but it is still difficult to estimate both E and P from the indentation data and EST alone. Herein an analytical method is proposed based on EST using the cell indentation and surface geometry from the AFM measurements. We also demonstrate the reliability of our approach under various osmotic pressure conditions and simultaneously determine the values of P and E in epidermal monolayer cells of an Allium cepa L.", "classifications": [ { "id": "JPMJCR2121", "label": "JPMJCR2121", "researcher": "Minako Ueda", "type": "grant" }, { "id": "Tsugawa", "label": "Group Tsugawa", "parent": "Ueda", "type": "group" }, { "id": "Ueda", "label": "Group Ueda", "parent": "Ueda", "type": "group" }, { "id": "Ueda", "label": "Team Ueda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yuki", "last_name": "Yamasaki", "name": null }, { "creator_type": "author", "first_name": "Kazunori", "last_name": "Okano", "name": null }, { "creator_type": "author", "first_name": "Tetsuro", "last_name": "Mimura", "name": null }, { "creator_type": "author", "first_name": "Satoru", "last_name": "Tsugawa", "name": null }, { "creator_type": "author", "first_name": "Yoichiroh", "last_name": "Hosokawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/s00425-025-04683-4" }, "pmcid": { "normalized": "PMC12062186" }, "pmid": { "normalized": "40338312" } }, "mesh": [ { "descriptor": "Biomechanical Phenomena", "descriptor_ui": "D001696", "major_topic": false }, { "descriptor": "Cell Wall", "descriptor_ui": "D002473", "major_topic": true }, { "descriptor": "Elasticity", "descriptor_ui": "D004548", "major_topic": true }, { "descriptor": "Microscopy, Atomic Force", "descriptor_ui": "D018625", "major_topic": true }, { "descriptor": "Onions", "descriptor_ui": "D019697", "major_topic": true }, { "descriptor": "Osmotic Pressure", "descriptor_ui": "D009997", "major_topic": false }, { "descriptor": "Plant Cells", "descriptor_ui": "D059828", "major_topic": true }, { "descriptor": "Pressure", "descriptor_ui": "D011312", "major_topic": false } ], "publication": { "conference_name": null, "date": "2025 May 8", "date_precision": "day", "issue": "6", "normalized_date": "2025-05-08", "pages": "131", "proceedings_title": null, "publisher": "", "title": "Planta", "volume": "261", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Simultaneous quantification of cell wall elasticity and turgor pressure in live plant cells by elastic shell theory analysis and AFM.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Enteroendocrine cells (EECs) are sensory epithelial cells that sense the gut luminal environment and convey sensory information to the brain via the visceral afferent pathway. Although EECs are a part of gut epithelial cells, which generally undergo rapid turnover, some EECs have been reported to be long-lived. EECs consist of multiple subtypes, each of which displays distinct hormone production and distribution patterns. It remains unknown whether a long lifespan is a characteristic shared by all EEC subtypes. To address this issue, we conducted genetic pulse labeling of three EEC subtypes expressing serotonin (5-HT), peptide YY (PYY), and gastric inhibitory polypeptide (GIP) in mice and tracked their survival. In the proximal small intestine, all labeled GIP(+) EECs disappeared completely within 5 days, whereas some PYY(+) EECs survived for more than 7 days. In the proximal colon, some labeled 5-HT(+) EECs lived for more than 28 days, whereas no PYY(+) cells survived beyond 14 days. These long-lived 5-HT(+) EECs were almost exclusively found in the upper half of the crypt in the mucosal fold, where visceral sensory fibers were enriched. This study reveals subtype- and region-dependent survival of EECs and suggests that EEC-nerve communication may underlie the long lifespan of certain EECs.", "classifications": [ { "id": "JPMJCR2021", "label": "JPMJCR2021", "researcher": "Hideki Enomoto", "type": "grant" }, { "id": "Enomoto", "label": "Group Enomoto", "parent": "Enomoto", "type": "group" }, { "id": "Enomoto", "label": "Team Enomoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Salsabila Luthfi", "last_name": "Sesotyosari", "name": null }, { "creator_type": "author", "first_name": "Masato", "last_name": "Kinoshita", "name": null }, { "creator_type": "author", "first_name": "Mukhamad", "last_name": "Sunardi", "name": null }, { "creator_type": "author", "first_name": "Mo", "last_name": "Lihan", "name": null }, { "creator_type": "author", "first_name": "Akimasa", "last_name": "Orii", "name": null }, { "creator_type": "author", "first_name": "Takaya", "last_name": "Abe", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Kiyonari", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Nakai", "name": null }, { "creator_type": "author", "first_name": "Toshihiro", "last_name": "Uesaka", "name": null }, { "creator_type": "author", "first_name": "Yuzo", "last_name": "Kodama", "name": null }, { "creator_type": "author", "first_name": "Hideki", "last_name": "Enomoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/dgd.70009" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "40342092" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Survival", "descriptor_ui": "D002470", "major_topic": false }, { "descriptor": "Enteroendocrine Cells", "descriptor_ui": "D019858", "major_topic": true }, { "descriptor": "Gastric Inhibitory Polypeptide", "descriptor_ui": "D005749", "major_topic": false }, { "descriptor": "Intestine, Small", "descriptor_ui": "D007421", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Peptide YY", "descriptor_ui": "D019894", "major_topic": false }, { "descriptor": "Serotonin", "descriptor_ui": "D012701", "major_topic": false } ], "publication": { "conference_name": null, "date": "2025 May 7", "date_precision": "day", "issue": "", "normalized_date": "2025-05-07", "pages": "", "proceedings_title": null, "publisher": "", "title": "Development, growth & differentiation", "volume": "", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "The long-term survival of enteroendocrine cells depends on their subtype and is linked to peripheral sensory innervation.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The gut microbiota confers host protection against pathogen colonization early after infection. Several mechanisms underlying the protection have been described, but the contributions of nutrient competition versus direct inhibition are controversial. Using an ex vivo model of Salmonella growth in the mouse cecum with its indigenous microbes, we find that nutrient limitation and typical inhibitory factors alone cannot prevent pathogen growth. However, the addition of certain amino acids markedly reverses the microbiota's ability to suppress pathogen growth. Enhanced Salmonella colonization after antibiotic treatment is ablated by exclusion of dietary protein, which requires the presence of the microbiota. Thus, dietary protein and amino acids are important regulators of colonization resistance.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Joseph M.", "last_name": "Pickard", "name": null }, { "creator_type": "author", "first_name": "Steffen", "last_name": "Porwollik", "name": null }, { "creator_type": "author", "first_name": "Gustavo", "last_name": "Caballero-Flores", "name": null }, { "creator_type": "author", "first_name": "Roberta", "last_name": "Caruso", "name": null }, { "creator_type": "author", "first_name": "Shinji", "last_name": "Fukuda", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Naohiro", "last_name": "Inohara", "name": null }, { "creator_type": "author", "first_name": "Michael", "last_name": "McClelland", "name": null }, { "creator_type": "author", "first_name": "Gabriel", "last_name": "Nunez", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41467-025-59706-1" }, "pmcid": { "normalized": "PMC12058977" }, "pmid": { "normalized": "40335509" } }, "mesh": [ { "descriptor": "Amino Acids", "descriptor_ui": "D000596", "major_topic": true }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Anti-Bacterial Agents", "descriptor_ui": "D000900", "major_topic": false }, { "descriptor": "Cecum", "descriptor_ui": "D002432", "major_topic": false }, { "descriptor": "Dietary Proteins", "descriptor_ui": "D004044", "major_topic": true }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Gastrointestinal Microbiome", "descriptor_ui": "D000069196", "major_topic": true }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Salmonella", "descriptor_ui": "D012475", "major_topic": true }, { "descriptor": "Salmonella Infections", "descriptor_ui": "D012480", "major_topic": false }, { "descriptor": "Salmonella typhimurium", "descriptor_ui": "D012486", "major_topic": true } ], "publication": { "conference_name": null, "date": "2025 May 7", "date_precision": "day", "issue": "1", "normalized_date": "2025-05-07", "pages": "4225", "proceedings_title": null, "publisher": "", "title": "Nature communications", "volume": "16", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Dietary amino acids regulate Salmonella colonization via microbiota-dependent mechanisms in the mouse gut.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The gsr-1 gene encodes the only glutathione reductase in Caenorhabditis elegans and gsr-1 loss-of-function alleles have a fully penetrant embryonic lethal phenotype. Therefore, maintenance of glutathione redox homeostasis is essential for nematode survival. We report here that impairment of the nonsense-mediated mRNA decay (NMD) pathway suppresses the embryonic lethality of gsr-1 mutants, allowing their normal development and growth. This NMD pathway dependent suppression requires cth-1 and cth-2 that encode two isoforms of cystathionine-gamma-lyase that catalyze the conversion of cystathionine to cysteine through the transsulfuration pathway. In contrast, the thioredoxin system that can also provide cysteine through the cystine reduction pathway appears to be dispensable for the suppression of the lethal phenotype of gsr-1 embryos when the NMD pathway is inactivated. Together, our data indicate that increasing the activity of the reverse transsulfuration pathway can compensate the detrimental effect of the gsr-1 mutation, raising the interesting question of why C. elegans has not preserved such compensatory mechanism to avoid the embryonic lethality of these mutants.", "classifications": [ { "id": "Onami", "label": "Group Onami", "parent": "Fujiwara", "type": "group" }, { "id": "Fujiwara", "label": "Team Fujiwara", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Marina", "last_name": "Valenzuela-Villatoro", "name": null }, { "creator_type": "author", "first_name": "Eva", "last_name": "Gomez-Orte", "name": null }, { "creator_type": "author", "first_name": "David", "last_name": "Guerrero-Gomez", "name": null }, { "creator_type": "author", "first_name": "Qing", "last_name": "Cheng", "name": null }, { "creator_type": "author", "first_name": "Angelina", "last_name": "Zheleva", "name": null }, { "creator_type": "author", "first_name": "Jose Antonio", "last_name": "Mora-Lorca", "name": null }, { "creator_type": "author", "first_name": "Dunja", "last_name": "Petrovic", "name": null }, { "creator_type": "author", "first_name": "Nigel J.", "last_name": "O Neil", "name": null }, { "creator_type": "author", "first_name": "Julian", "last_name": "Ceron Madrigal", "name": null }, { "creator_type": "author", "first_name": "Akiko", "last_name": "Hatakeyama", "name": null }, { "creator_type": "author", "first_name": "Shuichi", "last_name": "Onami", "name": null }, { "creator_type": "author", "first_name": "Alexandra", "last_name": "Ordonez-Luque", "name": null }, { "creator_type": "author", "first_name": "Cristina", "last_name": "Ayuso", "name": null }, { "creator_type": "author", "first_name": "Peter", "last_name": "Askjaer", "name": null }, { "creator_type": "author", "first_name": "Milos", "last_name": "Filipovic", "name": null }, { "creator_type": "author", "first_name": "Elias S. J.", "last_name": "Arner", "name": null }, { "creator_type": "author", "first_name": "Juan", "last_name": "Cabello", "name": null }, { "creator_type": "author", "first_name": "Antonio", "last_name": "Miranda-Vizuete", "name": null } ], "identifiers": { "doi": { "normalized": "10.1093/g3journal/jkaf102" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "40333285" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Caenorhabditis elegans", "descriptor_ui": "D017173", "major_topic": true }, { "descriptor": "Caenorhabditis elegans Proteins", "descriptor_ui": "D029742", "major_topic": true }, { "descriptor": "Embryo, Nonmammalian", "descriptor_ui": "D004625", "major_topic": false }, { "descriptor": "Genes, Lethal", "descriptor_ui": "D005804", "major_topic": false }, { "descriptor": "Glutathione Reductase", "descriptor_ui": "D005980", "major_topic": true }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": true }, { "descriptor": "Nonsense Mediated mRNA Decay", "descriptor_ui": "D059365", "major_topic": false }, { "descriptor": "Phenotype", "descriptor_ui": "D010641", "major_topic": false } ], "publication": { "conference_name": null, "date": "2025 May 7", "date_precision": "day", "issue": "", "normalized_date": "2025-05-07", "pages": "jkaf102", "proceedings_title": null, "publisher": "", "title": "G3 (Bethesda, Md.)", "volume": "", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "The transsulfuration pathway suppresses the embryonic lethal phenotype of glutathione reductase mutants in Caenorhabditis elegans.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The direct reprogramming of cells has tremendous potential in in vitro neurological studies. Previous attempts to convert blood cells into induced neurons have presented several challenges, necessitating a less invasive, efficient, rapid, and convenient approach. The current study introduces an optimized method for converting somatic cells into neurons using a nonsurgical approach that employs peripheral blood cells as an alternative source to fibroblasts. We have demonstrated the efficacy of a unique combination of transcription factors, including NEUROD1, and four Yamanaka reprogramming factors (OCT3/4, SOX2, KLF4, and c-MYC), in generating glutamatergic neurons within 3 wk. This approach, which requires only five pivotal factors (NEUROD1, OCT3/4, SOX2, KLF4, and c-MYC), has the potential to create functional neurons and circumvents the need for induced pluripotent stem cell (iPSC) intermediates, as evidenced by single-cell RNA sequencing and whole-genome bisulfite sequencing, along with lineage-tracing experiments using Cre-LoxP system. While fibroblasts have been widely used for neuronal reprogramming, our findings suggest that peripheral blood cells offer a potential alternative, particularly in contexts where minimally invasive sampling and procedures convenient for patients are emphasized. This method provides a rapid strategy for modeling neuronal diseases and contributes to advancements in drug discovery and personalized medicine.", "classifications": [ { "id": "JPMJCR2124", "label": "JPMJCR2124", "researcher": "Hirofumi Shintaku", "type": "grant" }, { "id": "Shintaku", "label": "Group Shintaku", "parent": "Shintaku", "type": "group" }, { "id": "Shintaku", "label": "Team Shintaku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yoichi", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Mitsuru", "last_name": "Ishikawa", "name": null }, { "creator_type": "author", "first_name": "Mahito", "last_name": "Ohkuma", "name": null }, { "creator_type": "author", "first_name": "Jonathan", "last_name": "Moody", "name": null }, { "creator_type": "author", "first_name": "Yo", "last_name": "Mabuchi", "name": null }, { "creator_type": "author", "first_name": "Tsukasa", "last_name": "Sanosaka", "name": null }, { "creator_type": "author", "first_name": "Yoshinari", "last_name": "Ando", "name": null }, { "creator_type": "author", "first_name": "Takayuki", "last_name": "Yamashita", "name": null }, { "creator_type": "author", "first_name": "Chung Chau", "last_name": "Hon", "name": null }, { "creator_type": "author", "first_name": "Jay W.", "last_name": "Shin", "name": null }, { "creator_type": "author", "first_name": "Wado", "last_name": "Akamatsu", "name": null }, { "creator_type": "author", "first_name": "Hideyuki", "last_name": "Okano", "name": null } ], "identifiers": { "doi": { "normalized": "10.1073/pnas.2401387122" }, "pmcid": { "normalized": "PMC12067290" }, "pmid": { "normalized": "40299704" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Basic Helix-Loop-Helix Proteins", "descriptor_ui": "D051792", "major_topic": true }, { "descriptor": "Blood Cells", "descriptor_ui": "D001773", "major_topic": true }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Cellular Reprogramming", "descriptor_ui": "D065150", "major_topic": true }, { "descriptor": "Fibroblasts", "descriptor_ui": "D005347", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Induced Pluripotent Stem Cells", "descriptor_ui": "D057026", "major_topic": false }, { "descriptor": "Kruppel-Like Factor 4", "descriptor_ui": "D000090062", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Nerve Tissue Proteins", "descriptor_ui": "D009419", "major_topic": true }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": true } ], "publication": { "conference_name": null, "date": "2025 May 6", "date_precision": "day", "issue": "18", "normalized_date": "2025-05-06", "pages": "e2401387122", "proceedings_title": null, "publisher": "", "title": "Proceedings of the National Academy of Sciences of the United States of America", "volume": "122", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "NEUROD1 efficiently converts peripheral blood cells into neurons with partial reprogramming by pluripotency factors.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Pancreatic ductal adenocarcinomas (PDACs) with wild-type KRAS constitute a small fraction of PDACs, and these tumors were recently shown to harbor frequent actionable oncogenic mutations and fusions. However, the clinicopathological features of KRAS wild-type PDAC have not been well studied. Additionally, precancerous lesions occurring in patients with KRAS wild-type PDACs have rarely been characterized. Here, we investigated the clinicopathological characteristics and outcomes of 75 patients with KRAS wild-type PDAC. Molecular analyses were performed in 40 patients using targeted DNA and whole-exome sequencing and targeted RNA sequencing. We demonstrated that patients with metastatic PDAC with wild-type KRAS were younger (median 59.5 years) than those with mutated KRAS (median 67 years, p < 0.000055). The wild-type KRAS status was not a significant prognostic factor for metastatic disease. Molecularly, genes in the RAS pathway are frequently mutated or rearranged (46%, 16/35), including mutations in BRAF, NRAS, HRAS, EGFR, MAP2K1, FGFR1, FGFR3 and ERBB4 and fusions of FGFR2 (FGFR2::CCDC147, FGFR2::CAT, FGFR2::TXLNA), ALK (STRN::ALK, EML4::ALK), and BRAF (TRIP11::BRAF). Mismatch repair deficiency was identified in 10% (4/39) of patients. Potentially actionable alterations were identified frequently in KRAS wild-type PDACs (30%, 12/40), in which nontubular-type carcinomas were significantly enriched with actionable alterations compared with tubular adenocarcinomas [67% (6/9) versus 16% (5/31); p = 0.007]. Finally, we investigated the precursors of PDACs in 13 pancreatectomy specimens from patients with KRAS wild-type PDAC. We identified three pancreatic intraepithelial neoplasias (PanINs) and two intraductal papillary mucinous neoplasms (IPMNs) harboring oncogenic fusions of ALK and BRAF and driver mutations in BRAF and AKT1. This study suggests that in the context of unmutated KRAS, PDAC is driven by alternative oncogenic mutations or fusions of RAS pathway genes, which may be introduced during the early phase of tumorigenesis. (c) 2025 The Author(s). The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Kazuhiro", "last_name": "Toriyama", "name": null }, { "creator_type": "author", "first_name": "Katsuhiro", "last_name": "Masago", "name": null }, { "creator_type": "author", "first_name": "Noriko", "last_name": "Shibata", "name": null }, { "creator_type": "author", "first_name": "Masataka", "last_name": "Haneda", "name": null }, { "creator_type": "author", "first_name": "Takamichi", "last_name": "Kuwahara", "name": null }, { "creator_type": "author", "first_name": "Seiji", "last_name": "Natsume", "name": null }, { "creator_type": "author", "first_name": "Shota", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Yasuko", "last_name": "Fujita", "name": null }, { "creator_type": "author", "first_name": "Eiichi", "last_name": "Sasaki", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Yamao", "name": null }, { "creator_type": "author", "first_name": "Hiroki", "last_name": "Kawashima", "name": null }, { "creator_type": "author", "first_name": "Yasuhiro", "last_name": "Shimizu", "name": null }, { "creator_type": "author", "first_name": "Kazuo", "last_name": "Hara", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null }, { "creator_type": "author", "first_name": "Waki", "last_name": "Hosoda", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/path.6432" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "40317966" } }, "mesh": [ { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Aged, 80 and over", "descriptor_ui": "D000369", "major_topic": false }, { "descriptor": "Biomarkers, Tumor", "descriptor_ui": "D014408", "major_topic": true }, { "descriptor": "Carcinoma, Pancreatic Ductal", "descriptor_ui": "D021441", "major_topic": true }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": true }, { "descriptor": "Pancreatic Neoplasms", "descriptor_ui": "D010190", "major_topic": true }, { "descriptor": "Precancerous Conditions", "descriptor_ui": "D011230", "major_topic": true }, { "descriptor": "Proto-Oncogene Proteins p21(ras)", "descriptor_ui": "D016283", "major_topic": true }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false } ], "publication": { "conference_name": null, "date": "2025 May 2", "date_precision": "day", "issue": "", "normalized_date": "2025-05-02", "pages": "", "proceedings_title": null, "publisher": "", "title": "The Journal of pathology", "volume": "", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Clinicopathological and molecular characterization of KRAS wild-type pancreatic ductal adenocarcinomas reveals precursor lesions with oncogenic mutations and fusions in RAS pathway genes.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Radical cyclizations are powerful tools for complexity building, providing facile access to functionalized cyclic adducts. However, forging two contiguous tetrasubstituted carbons via radical cyclization through the addition of tertiary radicals to geminally disubstituted sp(2) carbons has rarely been investigated. Furthermore, the effect of double-bond geometry at the geminally disubstituted sp(2) carbon on reactivity and stereochemical outcomes remains underexplored. In this study, we present experimental and computational studies on the carbooxygenation of 2-fluoro-3-aryl-allyl nitroacetates to investigate reactivity and selectivity differences between (E)- and (Z)-isomers. First, we identify that (E)-isomers are less reactive than (Z)-isomers. Second, both (E)- and (Z)-isomers undergo conversion to alpha,alpha,beta,beta-tetrasubstituted gamma-lactones with high syn-selectivity, despite the absence of putative E/Z isomerization of the alkene unit. Third, incorporating an electron-donating group at the radical acceptor enhances the reactivity of (E)-isomers in catalytic aerobic carbooxygenation. Fourth, computational studies show that syn-selectivity is mainly governed by the fluorine-induced gauche effect, whereas SOMO-HOMO level inversion induced by the electron-donating group at the radical acceptor enhances (E)-isomer reactivity. Based on these mechanistic insights, we develop a diastereoconvergent protocol using the E/Z mixture as a starting material to synthesize a potent antifungal agent.", "classifications": [ { "id": "Sodeoka", "label": "Group Sodeoka", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yanzong", "last_name": "Lyu", "name": null }, { "creator_type": "author", "first_name": "Florian", "last_name": "Punner", "name": null }, { "creator_type": "author", "first_name": "Mai", "last_name": "Akakabe", "name": null }, { "creator_type": "author", "first_name": "Yoshihiro", "last_name": "Sohtome", "name": null }, { "creator_type": "author", "first_name": "Mikiko", "last_name": "Sodeoka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/asia.202500336" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "40318140" } }, "mesh": [], "publication": { "conference_name": null, "date": "2025 May 2", "date_precision": "day", "issue": "", "normalized_date": "2025-05-02", "pages": "e202500336", "proceedings_title": null, "publisher": "", "title": "Chemistry, an Asian journal", "volume": "", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Factors Controlling Diastereoselectivity and Reactivity in the Catalytic Aerobic Carbooxygenation of (E)-2-Fluoro-3-aryl-allyl Nitroacetates.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Microscopic analyses of cytoskeleton organization are crucial for understanding various cellular activities, including cell proliferation and environmental responses in plants. Traditionally, assessments of cytoskeleton dynamics have been qualitative, relying on microscopy-assisted visual inspection. However, the transition to quantitative digital microscopy has introduced new technical challenges, with segmentation of cytoskeleton structures proving particularly demanding. In this study, we examined the utility of a deep learning-based segmentation method for accurate quantitative evaluation of cytoskeleton organization using confocal microscopic images of the cortical microtubules in tobacco BY-2 cells. The results showed that, although conventional methods sufficed for measurement of cytoskeleton angles and parallelness, the deep learning-based method significantly improved the accuracy of density measurements. To assess the versatility of the method, we extended our analysis to physiologically significant models in the context of changes in cytoskeleton density, namely Arabidopsis thaliana guard cells and zygotes. The deep learning-based method successfully improved the accuracy of cytoskeleton density measurements for quantitative evaluations of physiological changes in both stomatal movement in guard cells and intracellular polarization in elongating zygotes, confirming its utility in these applications. The results demonstrate the effectiveness of deep learning-based segmentation in providing precise and high-throughput measurements of cytoskeleton density, and has the potential to automate and expedite analyses of large-scale image datasets.", "classifications": [ { "id": "JPMJCR2121", "label": "JPMJCR2121", "researcher": "Minako Ueda", "type": "grant" }, { "id": "Higaki", "label": "Group Higaki", "parent": "Ueda", "type": "group" }, { "id": "Ueda", "label": "Group Ueda", "parent": "Ueda", "type": "group" }, { "id": "Ueda", "label": "Team Ueda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Ryota", "last_name": "Horiuchi", "name": null }, { "creator_type": "author", "first_name": "Asuka", "last_name": "Kamimura", "name": null }, { "creator_type": "author", "first_name": "Yuga", "last_name": "Hanaki", "name": null }, { "creator_type": "author", "first_name": "Hikari", "last_name": "Matsumoto", "name": null }, { "creator_type": "author", "first_name": "Minako", "last_name": "Ueda", "name": null }, { "creator_type": "author", "first_name": "Takumi", "last_name": "Higaki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/s00709-024-02019-9" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "39692866" } }, "mesh": [ { "descriptor": "Arabidopsis", "descriptor_ui": "D017360", "major_topic": false }, { "descriptor": "Cytoskeleton", "descriptor_ui": "D003599", "major_topic": true }, { "descriptor": "Deep Learning", "descriptor_ui": "D000077321", "major_topic": true }, { "descriptor": "Microtubules", "descriptor_ui": "D008870", "major_topic": false }, { "descriptor": "Nicotiana", "descriptor_ui": "D014026", "major_topic": false } ], "publication": { "conference_name": null, "date": "2025-05", "date_precision": "month", "issue": "3", "normalized_date": "2025-05", "pages": "739-751", "proceedings_title": null, "publisher": "", "title": "Protoplasma", "volume": "262", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Deep learning-based cytoskeleton segmentation for accurate high-throughput measurement of cytoskeleton density", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "There is currently a global epidemic of obesity and obesity-related diseases such as type 2 diabetes due to decreased physical activity, excessive food intake, and/or genetic predisposition. The Hippo-YAP1 pathway has attracted attention as a potential therapeutic target because YAP1/TAZ activation in murine immature adipocytes in vitro suppresses their differentiation by inhibiting PPARgamma activity. However, the role of YAP1 activation in mature adipocytes in vivo remains unclear. MOB1, whose expression is increased in obesity, is the hub of the Hippo core molecule complex and negatively regulates YAP1/TAZ activation. Therefore, we generated aMob1DKO mutant mice, which feature deficiency of Mob1a/b specifically in mature adipocytes. Compared to controls, aMob1DKO mice subjected to a high-fat diet showed beneficial changes consistent with resistance to diet-induced obesity. The mutants exhibited increases in basal lipolysis, \"beiging,\" and energy expenditure, as well as suppression of ROS production and inflammation in white adipose tissue. Insulin sensitivity and glucose tolerance were improved, and ectopic fat accumulation was reduced. Most of these changes were dependent on the YAP1 activation observed in mature white adipose tissue of aMob1DKO mice. FGF21, which improves lipid metabolism, was upregulated directly via YAP1 activation, and many of the phenotypes seen in aMob1DKO mice were also dependent on FGF21. Thus, the aMob1DKO mouse is an interesting model for the study of the metabolic effects of diet-induced obesity and protection against diabetes. Our work suggests that a YAP1-FGF21 axis exists in adipocytes that may be a potential therapeutic target for obesity.", "classifications": [ { "id": "JPMJCR2123", "label": "JPMJCR2123", "researcher": "Shinya Kuroda", "type": "grant" }, { "id": "Kuroda", "label": "Group Kuroda", "parent": "Kuroda", "type": "group" }, { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Miki", "last_name": "Nishio", "name": null }, { "creator_type": "author", "first_name": "Keiko", "last_name": "Yamaguchi", "name": null }, { "creator_type": "author", "first_name": "Junji", "last_name": "Otani", "name": null }, { "creator_type": "author", "first_name": "Katsuya", "last_name": "Yuguchi", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Kohno", "name": null }, { "creator_type": "author", "first_name": "Tsutomu", "last_name": "Sasaki", "name": null }, { "creator_type": "author", "first_name": "Tadahiro", "last_name": "Kitamura", "name": null }, { "creator_type": "author", "first_name": "Masakazu", "last_name": "Shinohara", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Koichi", "last_name": "Kawamura", "name": null }, { "creator_type": "author", "first_name": "Atsuo T.", "last_name": "Sasaki", "name": null }, { "creator_type": "author", "first_name": "Masashi", "last_name": "Oshima", "name": null }, { "creator_type": "author", "first_name": "Hiroki", "last_name": "Hikasa", "name": null }, { "creator_type": "author", "first_name": "Minna", "last_name": "Woo", "name": null }, { "creator_type": "author", "first_name": "Takehiko", "last_name": "Sasaki", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Nishina", "name": null }, { "creator_type": "author", "first_name": "Kazuwa", "last_name": "Nakao", "name": null }, { "creator_type": "author", "first_name": "Tomohiko", "last_name": "Maehama", "name": null }, { "creator_type": "author", "first_name": "Akira", "last_name": "Suzuki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1073/pnas.2424741122" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "40258148" } }, "mesh": [ { "descriptor": "Adaptor Proteins, Signal Transducing", "descriptor_ui": "D048868", "major_topic": true }, { "descriptor": "Adipocytes", "descriptor_ui": "D017667", "major_topic": true }, { "descriptor": "Adipose Tissue, White", "descriptor_ui": "D052436", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Diabetes Mellitus, Type 2", "descriptor_ui": "D003924", "major_topic": true }, { "descriptor": "Diet, High-Fat", "descriptor_ui": "D059305", "major_topic": false }, { "descriptor": "Energy Metabolism", "descriptor_ui": "D004734", "major_topic": false }, { "descriptor": "Fibroblast Growth Factors", "descriptor_ui": "D005346", "major_topic": false }, { "descriptor": "Insulin Resistance", "descriptor_ui": "D007333", "major_topic": false }, { "descriptor": "Lipolysis", "descriptor_ui": "D008066", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Obesity", "descriptor_ui": "D009765", "major_topic": true }, { "descriptor": "YAP-Signaling Proteins", "descriptor_ui": "D000091102", "major_topic": false } ], "publication": { "conference_name": null, "date": "2025 Apr 29", "date_precision": "day", "issue": "17", "normalized_date": "2025-04-29", "pages": "e2424741122", "proceedings_title": null, "publisher": "", "title": "Proceedings of the National Academy of Sciences of the United States of America", "volume": "122", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "MOB1 deletion in murine mature adipocytes ameliorates obesity and diabetes.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "", "classifications": [ { "id": "Hamamoto", "label": "Group Hamamoto", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Ryuji", "last_name": "Hamamoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.31662/jmaj.2025-0076" }, "pmcid": { "normalized": "PMC12095351" }, "pmid": { "normalized": "40416027" } }, "mesh": [], "publication": { "conference_name": null, "date": "2025 Apr 28", "date_precision": "day", "issue": "2", "normalized_date": "2025-04-28", "pages": "361-362", "proceedings_title": null, "publisher": "", "title": "JMA journal", "volume": "8", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Editorial for Innovative Artificial Intelligence System in the Children's Hospital in Japan.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Endoscopic ultrasound-guided fine-needle aspiration/biopsy (EUS-FNA/B) is critical for determining treatment strategies for patients with pancreatic cancer. However, conventional pathological examination using hematoxylin and eosin (H&E) staining is time-consuming. Microscopy with ultraviolet surface excitation (MUSE) enables rapid pathological diagnosis without requiring slide preparation. This study explores the potential of combining MUSE imaging with a cycle-consistent generative adversarial network (CycleGAN), an image generation algorithm capable of learning translations without paired images, to enhance diagnostic workflows for pancreatic EUS-FNA/B. Thirty-five pancreatic specimens were stained with Terbium/Hoechst 33342, and deep ultraviolet (DUV) fluorescence images were captured by exciting the tissue surface. These fluorescence images, along with H&E-stained formalin-fixed, paraffin-embedded (FFPE) sections from the same specimens, were divided into 256 x 256-pixel segments for CycleGAN training. The algorithm was employed to translate pseudo-H&E images from MUSE test images. The pseudo-H&E images generated by the CycleGAN showed improved inter-pathologist agreement among three pathologists compared with the original MUSE images. We established a technique to perform MUSE imaging on small pancreatic samples obtained through EUS-FNA/B and confirmed that H&E-style translation using CycleGAN simplified interpretation for pathologists. Integrating MUSE imaging with CycleGAN has the potential to offer a rapid, cost-effective, and accurate diagnostic tool.", "classifications": [ { "id": "Tanaka", "label": "Group Tanaka", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yuki", "last_name": "Koyama", "name": null }, { "creator_type": "author", "first_name": "Ryuta", "last_name": "Nakao", "name": null }, { "creator_type": "author", "first_name": "Junya", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Mizuki", "last_name": "Honda", "name": null }, { "creator_type": "author", "first_name": "Osamu", "last_name": "Inamori", "name": null }, { "creator_type": "author", "first_name": "Noriyuki", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Yukiko", "last_name": "Morinaga", "name": null }, { "creator_type": "author", "first_name": "Eiichi", "last_name": "Konishi", "name": null }, { "creator_type": "author", "first_name": "Yoshinori", "last_name": "Harada", "name": null }, { "creator_type": "author", "first_name": "Hideo", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Hiroaki", "last_name": "Yasuda", "name": null }, { "creator_type": "author", "first_name": "Yoshito", "last_name": "Itoh", "name": null }, { "creator_type": "author", "first_name": "Hajime", "last_name": "Nagahara", "name": null }, { "creator_type": "author", "first_name": "Hirohiko", "last_name": "Niioka", "name": null }, { "creator_type": "author", "first_name": "Tetsuro", "last_name": "Takamatsu", "name": null } ], "identifiers": { "doi": { "normalized": "10.1267/ahc.25-00007" }, "pmcid": { "normalized": "PMC12173637" }, "pmid": { "normalized": "40535473" } }, "mesh": [], "publication": { "conference_name": null, "date": "2025 Apr 26", "date_precision": "day", "issue": "2", "normalized_date": "2025-04-26", "pages": "59-67", "proceedings_title": null, "publisher": "", "title": "Acta histochemica et cytochemica", "volume": "58", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "H&E Style Translation Using CycleGAN for Deep Ultraviolet-Excitation Fluorescence Images of Pancreatic Endoscopic Ultrasound-Fine Needle Aspiration/Biopsy Toward Slide-Free Rapid Pathology.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Radiolabeled glucagon-like peptide 1 (GLP- 1) analog scintigraphy is a new, high-sensitivity imaging method for detecting small insulinomas. Somatostatin receptor scintigraphy (SRS) is an established method for detecting gastroenteropancreatic neuroendocrine tumors. However, small benign insulinomas are difficult to detect using SRS. Furthermore, GLP- 1 receptor (GLP- 1R) expression and SRS results may be inversely correlated. We identified 689 neuroendocrine neoplasms, including pancreatic neuroendocrine tumors (PanNETs) and neuroendocrine neoplasms originating from non-pancreatic sites, and performed GLP- 1R immunostaining. Among the non-insulinoma PanNETs, immunohistochemical insulin or proinsulin positive cases were categorized as Ins(pos), and both negative cases as Ins(neg). High prevalence of GLP- 1R expression was detected in PanNETs and duodenal NETs (34% and 53%, respectively). Some pulmonary NETs were GLP- 1R positive (9%). In contrast, neither GI-NEC excluding one case nor pulmonary NEC exhibited GLP- 1R expression. The percentage of GLP- 1R positive cases for Ins(pos), Ins(neg), and insulinoma was 31%, 0%, and 84%, respectively. Among PanNETs, GLP- 1R positive cases showed higher expression of insulin and proinsulin than negative cases. SRS-positive patients showed lower expression levels of insulin, proinsulin, and GLP- 1R than SRS-negative patients. The expression in PanNETs and duodenal NETs may be derived from the expression in their normal counterparts. Insulinoma and Ins(pos) cases showed GLP- 1R expression. Furthermore, as GLP- 1R-positive patients showed significantly higher expression of insulin and proinsulin than GLP- 1R negative patients, GLP- 1R may also be associated with neoplastic insulin production and GLP- 1 analog scintigraphy may detect subclinical insulinomas. In addition, SRS-negative cases showed significantly higher GLP- 1R expression than SRS-positive cases. These results suggest the application potential of GLP- 1 analog scintigraphy in combination with SRS as a detection tool.", "classifications": [ { "id": "Suzuki", "label": "Group Suzuki", "parent": "Takekawa", "type": "group" }, { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" }, { "id": "Takekawa", "label": "Team Takekawa", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Hirofumi", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Fumiyoshi", "last_name": "Fujishima", "name": null }, { "creator_type": "author", "first_name": "Yuto", "last_name": "Yamazaki", "name": null }, { "creator_type": "author", "first_name": "Masayuki", "last_name": "Imamura", "name": null }, { "creator_type": "author", "first_name": "Susumu", "last_name": "Hijioka", "name": null }, { "creator_type": "author", "first_name": "Kazuo", "last_name": "Hara", "name": null }, { "creator_type": "author", "first_name": "Takamichi", "last_name": "Kuwahara", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null }, { "creator_type": "author", "first_name": "Kazuhiro", "last_name": "Sakamoto", "name": null }, { "creator_type": "author", "first_name": "Hisashi", "last_name": "Shiga", "name": null }, { "creator_type": "author", "first_name": "Tomohiro", "last_name": "Kawaguchi", "name": null }, { "creator_type": "author", "first_name": "Hiroyoshi", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Yumi", "last_name": "Kanbayashi", "name": null }, { "creator_type": "author", "first_name": "Akira", "last_name": "Ohkoshi", "name": null }, { "creator_type": "author", "first_name": "Muneaki", "last_name": "Shimada", "name": null }, { "creator_type": "author", "first_name": "Hiromichi", "last_name": "Niikawa", "name": null }, { "creator_type": "author", "first_name": "Mami", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Fujio", "name": null }, { "creator_type": "author", "first_name": "Toshihiko", "last_name": "Masui", "name": null }, { "creator_type": "author", "first_name": "Yosuke", "last_name": "Kasai", "name": null }, { "creator_type": "author", "first_name": "Hideki", "last_name": "Ota", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Ozawa", "name": null }, { "creator_type": "author", "first_name": "Hidenori", "last_name": "Endo", "name": null }, { "creator_type": "author", "first_name": "Michiaki", "last_name": "Unno", "name": null }, { "creator_type": "author", "first_name": "Hironobu", "last_name": "Sasano", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Suzuki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/s00428-025-04098-2" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "40281248" } }, "mesh": [ { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Aged, 80 and over", "descriptor_ui": "D000369", "major_topic": false }, { "descriptor": "Antibodies, Monoclonal", "descriptor_ui": "D000911", "major_topic": true }, { "descriptor": "Biomarkers, Tumor", "descriptor_ui": "D014408", "major_topic": true }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Glucagon-Like Peptide-1 Receptor", "descriptor_ui": "D000067757", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Immunohistochemistry", "descriptor_ui": "D007150", "major_topic": false }, { "descriptor": "Insulin", "descriptor_ui": "D007328", "major_topic": true }, { "descriptor": "Insulinoma", "descriptor_ui": "D007340", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Neoplasm Grading", "descriptor_ui": "D060787", "major_topic": false }, { "descriptor": "Neuroendocrine Tumors", "descriptor_ui": "D018358", "major_topic": true }, { "descriptor": "Pancreatic Neoplasms", "descriptor_ui": "D010190", "major_topic": true }, { "descriptor": "Radionuclide Imaging", "descriptor_ui": "D011877", "major_topic": false }, { "descriptor": "Receptors, Somatostatin", "descriptor_ui": "D017481", "major_topic": true }, { "descriptor": "Young Adult", "descriptor_ui": "D055815", "major_topic": false } ], "publication": { "conference_name": null, "date": "2025 Apr 26", "date_precision": "day", "issue": "", "normalized_date": "2025-04-26", "pages": "", "proceedings_title": null, "publisher": "", "title": "Virchows Archiv : an international journal of pathology", "volume": "", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "GLP- 1R status using validated monoclonal antibody in 689 cases of neuroendocrine neoplasm and its correlation with somatostatin receptor scintigraphy, insulin production, and histological grades.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Plasma amino acids (AAs) have emerged as promising biomarkers for metabolic disorders, yet their causality remains unclear. We aimed to investigate the genetic determinants of AA levels in a cohort of 10,333 individuals and their causal effects on cardiometabolic traits using Mendelian randomization (MR). Plasma levels of 20 AAs were quantified using capillary electrophoresis mass spectrometry. Genome-wide association studies were conducted using BOLT-LMM and heritability estimation via LDSC analysis. Causal effects of AAs on 11 cardiometabolic traits were examined using two-sample MR analyses. We identified 85 locus-metabolite associations across 43 genes for 18 AAs, including 44 novel loci linked to metabolic genes. Heritability for AAs was estimated at 16%. MR analysis demonstrated cystine to positively associate with systolic blood pressure (SBP) (beta = 0.056, SE = 0.010), while serine indicated protective effects on SBP (beta = - 0.040, SE = 0.011), diastolic BP (beta = - 0.044, SE = 0.010), and coronary artery disease (odds ratio 0.888, SE = 0.028). We identified potentially novel genetic loci associated with AA levels and demonstrated robust causal associations between several AAs and cardiometabolic traits. These findings reinforce the importance of AAs as potential biomarkers and therapeutic targets in cardiometabolic health.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Ryota", "last_name": "Toki", "name": null }, { "creator_type": "author", "first_name": "Sotaro", "last_name": "Fushiki", "name": null }, { "creator_type": "author", "first_name": "Shun", "last_name": "Kojima", "name": null }, { "creator_type": "author", "first_name": "Yoichi", "last_name": "Sutoh", "name": null }, { "creator_type": "author", "first_name": "Yayoi", "last_name": "Otsuka-Yamasaki", "name": null }, { "creator_type": "author", "first_name": "Sei", "last_name": "Harada", "name": null }, { "creator_type": "author", "first_name": "Miho", "last_name": "Iida", "name": null }, { "creator_type": "author", "first_name": "Aya", "last_name": "Hirata", "name": null }, { "creator_type": "author", "first_name": "Naoko", "last_name": "Miyagawa", "name": null }, { "creator_type": "author", "first_name": "Minako", "last_name": "Matsumoto", "name": null }, { "creator_type": "author", "first_name": "Shun", "last_name": "Edagawa", "name": null }, { "creator_type": "author", "first_name": "Atsuko", "last_name": "Miyake", "name": null }, { "creator_type": "author", "first_name": "Kazuyo", "last_name": "Kuwabara", "name": null }, { "creator_type": "author", "first_name": "Akiyoshi", "last_name": "Hirayama", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Sugimoto", "name": null }, { "creator_type": "author", "first_name": "Asako", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Kaori", "last_name": "Amano", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Masaru", "last_name": "Tomita", "name": null }, { "creator_type": "author", "first_name": "Kazuharu", "last_name": "Arakawa", "name": null }, { "creator_type": "author", "first_name": "Kengo", "last_name": "Kinoshita", "name": null }, { "creator_type": "author", "first_name": "Mika", "last_name": "Sakurai-Yageta", "name": null }, { "creator_type": "author", "first_name": "Gen", "last_name": "Tamiya", "name": null }, { "creator_type": "author", "first_name": "Hideki", "last_name": "Ohmomo", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Shimizu", "name": null }, { "creator_type": "author", "first_name": "Tomonori", "last_name": "Okamura", "name": null }, { "creator_type": "author", "first_name": "Toru", "last_name": "Takebayashi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41598-025-98992-z" }, "pmcid": { "normalized": "PMC12032298" }, "pmid": { "normalized": "40281240" } }, "mesh": [ { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Amino Acids", "descriptor_ui": "D000596", "major_topic": true }, { "descriptor": "Biomarkers", "descriptor_ui": "D015415", "major_topic": false }, { "descriptor": "Blood Pressure", "descriptor_ui": "D001794", "major_topic": false }, { "descriptor": "Cardiovascular Diseases", "descriptor_ui": "D002318", "major_topic": true }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Genome-Wide Association Study", "descriptor_ui": "D055106", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mendelian Randomization Analysis", "descriptor_ui": "D057182", "major_topic": true }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Polymorphism, Single Nucleotide", "descriptor_ui": "D020641", "major_topic": false } ], "publication": { "conference_name": null, "date": "2025 Apr 25", "date_precision": "day", "issue": "1", "normalized_date": "2025-04-25", "pages": "14569", "proceedings_title": null, "publisher": "", "title": "Scientific reports", "volume": "15", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Genome-wide association study of plasma amino acids and Mendelian randomization for cardiometabolic traits.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Genome-wide profiling of gene expression levels in cells, such as transcriptomics and proteomics, is a powerful experimental approach in modern biology, allowing not only efficient exploration of the genetic elements responsible for biological phenomena of interest, but also characterization of the global constraints behind plastic phenotypic changes of cells that accompany large-scale remodeling of omics profiles. To understand how individual cells change their molecular profiles to achieve specific phenotypic changes in phenomena such as differentiation, cancer metastasis and adaptation, it is crucial to characterize the dynamics of cellular phenotypes and omics profiles simultaneously at the single-cell level. Especially in the last decade, significant technical progress has been made in the in situ identification of omics profiles of cells on the microscope. However, most approaches still remain destructive and cannot unravel the post-measurement dynamics. In recent years, Raman spectroscopy-based methods for omics inference have emerged, allowing the characterization of genome-wide molecular profile dynamics in living cells. In this review, we give a brief overview of the recent development of imaging-based omics profiling methods. We then present the approach to infer omics profiles from single-cell Raman spectra. Since Raman spectra can be obtained from living cells in a non-destructive and non-staining manner, this method may open the door to live-cell omics.", "classifications": [ { "id": "JPMJCR1927", "label": "JPMJCR1927", "researcher": "Yuichi Wakamoto", "type": "grant" }, { "id": "Wakamoto", "label": "Group Wakamoto", "parent": "Wakamoto", "type": "group" }, { "id": "Wakamoto", "label": "Team Wakamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Ken-Ichiro F.", "last_name": "Kamei", "name": null }, { "creator_type": "author", "first_name": "Yuichi", "last_name": "Wakamoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1093/jmicro/dfaf020" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "40271815" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Gene Expression Profiling", "descriptor_ui": "D020869", "major_topic": true }, { "descriptor": "Genomics", "descriptor_ui": "D023281", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Proteomics", "descriptor_ui": "D040901", "major_topic": true }, { "descriptor": "Single-Cell Analysis", "descriptor_ui": "D059010", "major_topic": true }, { "descriptor": "Spectrum Analysis, Raman", "descriptor_ui": "D013059", "major_topic": true }, { "descriptor": "Transcriptome", "descriptor_ui": "D059467", "major_topic": false } ], "publication": { "conference_name": null, "date": "2025 Apr 24", "date_precision": "day", "issue": "", "normalized_date": "2025-04-24", "pages": "dfaf020", "proceedings_title": null, "publisher": "", "title": "Microscopy (Oxford, England)", "volume": "", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Live-cell omics with Raman spectroscopy.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: Efficiently assessing glucose handling capacity is a critical public health challenge. This study assessed the utility of relatively easy-to-measure continuous glucose monitoring (CGM)-derived indices in estimating glucose handling capacities calculated from resource-intensive clamp tests. METHODS: We conducted a prospective study of 64 individuals without prior diabetes diagnosis. The study performed CGM, oral glucose tolerance tests (OGTT), and hyperglycemic and hyperinsulinemic-euglycemic clamp tests. We validated CGM-derived indices characteristics using an independent dataset from another country and mathematical models with simulated data. RESULTS: A CGM-derived index reflecting the autocorrelation function of glucose levels (AC_Var) is significantly correlated with clamp-derived disposition index (DI), a well-established measure of glucose handling capacity and predictor of diabetes onset. Multivariate and machine learning models indicate AC_Var's contribution to predicting clamp-derived DI independent from other CGM-derived indices. The model using CGM-measured glucose standard deviation and AC_Var outperforms models using commonly used diabetes diagnostic indices, such as fasting blood glucose, HbA1c, and OGTT measures, in predicting clamp-derived DI. Mathematical simulations also demonstrate the association of AC_Var with DI. CONCLUSIONS: CGM-derived indices, including AC_Var, serve as valuable tools for predicting glucose handling capacities in populations without prior diabetes diagnosis. We develop a web application that calculates these CGM-derived indices ( https://cgm-ac-mean-std.streamlit.app/ ).", "classifications": [ { "id": "JPMJCR2123", "label": "JPMJCR2123", "researcher": "Shinya Kuroda", "type": "grant" }, { "id": "Kuroda", "label": "Group Kuroda", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Hikaru", "last_name": "Sugimoto", "name": null }, { "creator_type": "author", "first_name": "Ken-Ichi", "last_name": "Hironaka", "name": null }, { "creator_type": "author", "first_name": "Tomoaki", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Tomoko", "last_name": "Yamada", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Miura", "name": null }, { "creator_type": "author", "first_name": "Natsu", "last_name": "Otowa-Suematsu", "name": null }, { "creator_type": "author", "first_name": "Masashi", "last_name": "Fujii", "name": null }, { "creator_type": "author", "first_name": "Yushi", "last_name": "Hirota", "name": null }, { "creator_type": "author", "first_name": "Kazuhiko", "last_name": "Sakaguchi", "name": null }, { "creator_type": "author", "first_name": "Wataru", "last_name": "Ogawa", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Kuroda", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s43856-025-00819-5" }, "pmcid": { "normalized": "PMC12015487" }, "pmid": { "normalized": "40263561" } }, "mesh": [], "publication": { "conference_name": null, "date": "2025 Apr 22", "date_precision": "day", "issue": "1", "normalized_date": "2025-04-22", "pages": "103", "proceedings_title": null, "publisher": "", "title": "Communications medicine", "volume": "5", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Improved detection of decreased glucose handling capacities via continuous glucose monitoring-derived indices.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Adaptation to starvation is a multimolecular and temporally ordered process. We sought to elucidate how the healthy liver regulates various molecules in a temporally ordered manner during starvation and how obesity disrupts this process. We used multiomic data collected from the plasma and livers of wild-type and leptin-deficient obese (ob/ob) mice at multiple time points during starvation to construct a starvation-responsive metabolic network that included responsive molecules and their regulatory relationships. Analysis of the network structure showed that in wild-type mice, the key molecules for energy homeostasis, ATP and AMP, acted as hub molecules to regulate various metabolic reactions in the network. Although neither ATP nor AMP was responsive to starvation in ob/ob mice, the structural properties of the network were maintained. In wild-type mice, the molecules in the network were temporally ordered through metabolic processes coordinated by hub molecules, including ATP and AMP, and were positively or negatively coregulated. By contrast, both temporal order and coregulation were disrupted in ob/ob mice. These results suggest that the metabolic network that responds to starvation was structurally robust but temporally disrupted by the obesity-associated loss of responsiveness of the hub molecules. In addition, we propose how obesity alters the response to intermittent fasting.", "classifications": [ { "id": "Inaba", "label": "Group Inaba", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Group Kuroda", "parent": "Kuroda", "type": "group" }, { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Keigo", "last_name": "Morita", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Hatano", "name": null }, { "creator_type": "author", "first_name": "Toshiya", "last_name": "Kokaji", "name": null }, { "creator_type": "author", "first_name": "Hikaru", "last_name": "Sugimoto", "name": null }, { "creator_type": "author", "first_name": "Takaho", "last_name": "Tsuchiya", "name": null }, { "creator_type": "author", "first_name": "Haruka", "last_name": "Ozaki", "name": null }, { "creator_type": "author", "first_name": "Riku", "last_name": "Egami", "name": null }, { "creator_type": "author", "first_name": "Dongzi", "last_name": "Li", "name": null }, { "creator_type": "author", "first_name": "Akira", "last_name": "Terakawa", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Ohno", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Inoue", "name": null }, { "creator_type": "author", "first_name": "Yuka", "last_name": "Inaba", "name": null }, { "creator_type": "author", "first_name": "Yutaka", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Masaki", "last_name": "Matsumoto", "name": null }, { "creator_type": "author", "first_name": "Masatomo", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Yoshihiro", "last_name": "Izumi", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Bamba", "name": null }, { "creator_type": "author", "first_name": "Akiyoshi", "last_name": "Hirayama", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Kuroda", "name": null } ], "identifiers": { "doi": { "normalized": "10.1126/scisignal.ads2547" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "40261956" } }, "mesh": [ { "descriptor": "Adenosine Monophosphate", "descriptor_ui": "D000249", "major_topic": false }, { "descriptor": "Adenosine Triphosphate", "descriptor_ui": "D000255", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Energy Metabolism", "descriptor_ui": "D004734", "major_topic": false }, { "descriptor": "Leptin", "descriptor_ui": "D020738", "major_topic": false }, { "descriptor": "Liver", "descriptor_ui": "D008099", "major_topic": true }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Metabolic Networks and Pathways", "descriptor_ui": "D053858", "major_topic": true }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Obese", "descriptor_ui": "D008820", "major_topic": false }, { "descriptor": "Obesity", "descriptor_ui": "D009765", "major_topic": true }, { "descriptor": "Starvation", "descriptor_ui": "D013217", "major_topic": true } ], "publication": { "conference_name": null, "date": "2025 Apr 22", "date_precision": "day", "issue": "883", "normalized_date": "2025-04-22", "pages": "eads2547", "proceedings_title": null, "publisher": "", "title": "Science signaling", "volume": "18", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Structural robustness and temporal vulnerability of the starvation-responsive metabolic network in healthy and obese mouse liver.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: Liquid biopsy has been developed as an alternative to tissue-based sequencing for detecting genomic alterations in solid tumors. However, the clinical utility of liquid biopsy in patients with solid tumors for whom tissue-based next-generation sequencing (NGS) is infeasible has not been well-characterized, particularly in previously untreated individuals. METHODS: This prospective study evaluated the clinical impact of liquid biopsy, focusing on six solid tumor types. Overall, 109 patients were enrolled and underwent liquid biopsy using Guardant360 (Guardant Health, Redwood City, CA, USA). Among these, 94 (86.3%) patients were previously untreated. RESULTS: The most common cancer type was non-small cell lung cancer (n = 57, 52.3%), followed by pancreatic (n = 35, 32.1%), biliary tract (n = 8, 7.3%), gastric (n = 5, 4.6%), colorectal (n = 3, 2.8%), and triple-negative breast (n = 1, 0.9%) cancers. The success rate of liquid biopsy was 99.1%, and the median turnaround time from blood collection to results was 7 days (range: 5-22 days). Actionable alterations were detected in 31 (28.4%) patients, and 8.3% of them received matched therapy based on alterations identified by liquid biopsy. Among previously untreated patients, actionable mutations were identified in 29.8%, and 8.5% received matched therapy. CONCLUSIONS: In patients with advanced solid tumors for which tissue-based NGS is not feasible, performing upfront liquid biopsy could lead to the detection of actionable alterations and help guide targeted therapies. CLINICAL TRIAL REGISTRY: UMIN Clinical Trials Registry (UMIN000041722).", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Akito", "last_name": "Fukuda", "name": null }, { "creator_type": "author", "first_name": "Takaaki", "last_name": "Mizuno", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Kuniko", "last_name": "Sunami", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Kubo", "name": null }, { "creator_type": "author", "first_name": "Takafumi", "last_name": "Koyama", "name": null }, { "creator_type": "author", "first_name": "Kan", "last_name": "Yonemori", "name": null }, { "creator_type": "author", "first_name": "Takuji", "last_name": "Okusaka", "name": null }, { "creator_type": "author", "first_name": "Ken", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Yuichiro", "last_name": "Ohe", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null }, { "creator_type": "author", "first_name": "Noboru", "last_name": "Yamamoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1093/jjco/hyaf065" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "40251768" } }, "mesh": [ { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Aged, 80 and over", "descriptor_ui": "D000369", "major_topic": false }, { "descriptor": "Biomarkers, Tumor", "descriptor_ui": "D014408", "major_topic": true }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "High-Throughput Nucleotide Sequencing", "descriptor_ui": "D059014", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Liquid Biopsy", "descriptor_ui": "D000073890", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": false }, { "descriptor": "Neoplasms", "descriptor_ui": "D009369", "major_topic": true }, { "descriptor": "Prospective Studies", "descriptor_ui": "D011446", "major_topic": false } ], "publication": { "conference_name": null, "date": "2025 Apr 19", "date_precision": "day", "issue": "", "normalized_date": "2025-04-19", "pages": "hyaf065", "proceedings_title": null, "publisher": "", "title": "Japanese journal of clinical oncology", "volume": "", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Upfront liquid biopsy in patients with advanced solid tumors who were not feasible for tissue-based next-generation sequencing.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "OBJECTIVES: EGFR-tyrosine kinase inhibitors, including osimertinib, have revolutionized EGFR-mutated non-small cell lung cancer (NSCLC) treatment; therefore, early identification of EGFR mutations is essential. We report post-hoc analyses of pooled EGFR mutation tissue testing across osimertinib clinical trials, highlighting testing challenges and supporting best practice. MATERIALS AND METHODS: Pooled central Cobas(R) EGFR Mutation Test data from nine global osimertinib NSCLC clinical trials were analyzed by specimen type, disease stage, and geographical region for specimen adequacy for testing and valid test results. RESULTS: Across 4,864 biopsies and 2,402 resections, 91% were adequate for testing, of which 95% of biopsies and 99% of resections had valid test results. Of biopsies, 12% were inadequate for testing (mainly due to insufficient tumor content [42%] and insufficient tissue volume [35%]) and 3% of resections were inadequate (insufficient tumor content [55%] and incorrect specimen preparation [12%]). Inadequacy varied by disease stage, from 3% in resectable stage IA2-IIIA to 10%-15% in first and second/later-line advanced/metastatic settings, and 16% in unresectable stage III. Test success rates among adequate specimens ranged from 93% (unresectable stage III) to 99% (resectable stage IA2-IIIA). Data were similar by geography. DISCUSSION: Most tissue specimens were adequate for EGFR testing. Inadequacy was commonly due to insufficient tissue volume or tumor content and higher in biopsies versus resections, and unresectable stage III and first-line advanced/metastatic versus other disease stages. Based on these controlled trial data, pre-analytic variables of tissue specimens are a major driver of testing success; hence maintaining optimal conditions from sample collection to biomarker analysis, as well as improving tissue-sampling techniques is critical to increase testing success rates. TRIAL REGISTRATION NUMBERS: NCT01802632, NCT02094261, NCT02151981, NCT02296125, NCT04035486, NCT02511106, NCT05120349, NCT03521154, NCT04351555.", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Marie Laure", "last_name": "Murat-Onana", "name": null }, { "creator_type": "author", "first_name": "Suresh S.", "last_name": "Ramalingam", "name": null }, { "creator_type": "author", "first_name": "Pasi A.", "last_name": "Janne", "name": null }, { "creator_type": "author", "first_name": "Jhanelle E.", "last_name": "Gray", "name": null }, { "creator_type": "author", "first_name": "Myung-Ju", "last_name": "Ahn", "name": null }, { "creator_type": "author", "first_name": "Tom", "last_name": "John", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null }, { "creator_type": "author", "first_name": "Xiangning", "last_name": "Huang", "name": null }, { "creator_type": "author", "first_name": "Yuri", "last_name": "Rukazenkov", "name": null }, { "creator_type": "author", "first_name": "Manana", "last_name": "Javey", "name": null }, { "creator_type": "author", "first_name": "Helen", "last_name": "Brown", "name": null }, { "creator_type": "author", "first_name": "Xiaocheng", "last_name": "Li-Sucholeiki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.lungcan.2025.108549" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "40311309" } }, "mesh": [ { "descriptor": "Acrylamides", "descriptor_ui": "D000178", "major_topic": true }, { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Aniline Compounds", "descriptor_ui": "D000814", "major_topic": true }, { "descriptor": "Antineoplastic Agents", "descriptor_ui": "D000970", "major_topic": false }, { "descriptor": "Biopsy", "descriptor_ui": "D001706", "major_topic": false }, { "descriptor": "Carcinoma, Non-Small-Cell Lung", "descriptor_ui": "D002289", "major_topic": true }, { "descriptor": "Clinical Trials as Topic", "descriptor_ui": "D002986", "major_topic": false }, { "descriptor": "DNA Mutational Analysis", "descriptor_ui": "D004252", "major_topic": false }, { "descriptor": "ErbB Receptors", "descriptor_ui": "D066246", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Indoles", "descriptor_ui": "D007211", "major_topic": false }, { "descriptor": "Lung Neoplasms", "descriptor_ui": "D008175", "major_topic": true }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": true }, { "descriptor": "Neoplasm Staging", "descriptor_ui": "D009367", "major_topic": false }, { "descriptor": "Protein Kinase Inhibitors", "descriptor_ui": "D047428", "major_topic": false }, { "descriptor": "Pyrimidines", "descriptor_ui": "D011743", "major_topic": false } ], "publication": { "conference_name": null, "date": "2025 Apr 18", "date_precision": "day", "issue": "", "normalized_date": "2025-04-18", "pages": "108549", "proceedings_title": null, "publisher": "", "title": "Lung cancer (Amsterdam, Netherlands)", "volume": "204", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "EGFR mutation testing across the osimertinib clinical program.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Apical constriction is a basic mechanism for epithelial morphogenesis, making columnar cells into wedge shape and bending a flat cell sheet. It has long been thought that an apically localized myosin generates a contractile force and drives the cell deformation. However, when we tested the increased apical surface contractility in a cellular Potts model simulation, the constriction increased pressure inside the cell and pushed its lateral surface outward, making the cells adopt a drop shape instead of the expected wedge shape. To keep the lateral surface straight, we considered an alternative model in which the cell shape was determined by cell membrane elasticity and endocytosis, and the increased pressure is balanced among the cells. The cellular Potts model simulation succeeded in reproducing the apical constriction, and it also suggested that a too strong apical surface tension might prevent the tissue invagination.", "classifications": [ { "id": "Ishihara", "label": "Group Ishihara", "parent": "Sawai", "type": "group" }, { "id": "Sawai", "label": "Team Sawai", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Satoshi", "last_name": "Yamashita", "name": null }, { "creator_type": "author", "first_name": "Shuji", "last_name": "Ishihara", "name": null }, { "creator_type": "author", "first_name": "Francois", "last_name": "Graner", "name": null } ], "identifiers": { "doi": { "normalized": "10.7554/elife.93496" }, "pmcid": { "normalized": "PMC12005724" }, "pmid": { "normalized": "40243291" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Membrane", "descriptor_ui": "D002462", "major_topic": false }, { "descriptor": "Cell Shape", "descriptor_ui": "D048430", "major_topic": true }, { "descriptor": "Elasticity", "descriptor_ui": "D004548", "major_topic": false }, { "descriptor": "Endocytosis", "descriptor_ui": "D004705", "major_topic": false }, { "descriptor": "Epithelial Cells", "descriptor_ui": "D004847", "major_topic": true }, { "descriptor": "Models, Biological", "descriptor_ui": "D008954", "major_topic": false }, { "descriptor": "Surface Tension", "descriptor_ui": "D013500", "major_topic": false } ], "publication": { "conference_name": null, "date": "2025 Apr 17", "date_precision": "day", "issue": "", "normalized_date": "2025-04-17", "pages": "", "proceedings_title": null, "publisher": "", "title": "eLife", "volume": "13", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Apical constriction requires patterned apical surface remodeling to synchronize cellular deformation.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "In the present study, a planar laser induced fluorescence (P-LIF) measurement, reaction rate measurement, the sonochemical luminescence (SCL) observation, and the particle image velocimetry (PIV) measurement were conducted to clarify the effect of macroscopic mass transfer on sonochemical reaction rate in an ultrasonic bath. The concentration distribution was measured by the fluorescence intensity of Rhodamine 6G (Rh6G), which was illuminated by a CW-YAG laser sheet. The concentration of Rh6G decreases first in the high reaction zone measured by the SCL observation, and the resulting low-concentration zone expands to the low reaction zone through macroscopic convective mass transfer, which can be observed as solute plumes. Therefore, it is concluded that the mass transfer rate can slightly affect the chemical reaction rate due to the nonuniform concentration distribution in the early stage of sonochemical reaction. The reaction rate is slightly underestimated due to the spatial variation of the concentration in the early stage of ultrasonic degradation. The effect of macroscopic mass transfer on the sonochemical reaction rate was evaluated by first Damkohler number, which was calculated based on the flow velocity obtained by the PIV measurement and the reaction rate constant obtained by the decomposition experiment. Finally, it could be concluded that the first Damkohler number evaluates the effect of macroscopic mass transfer on the sonochemical reaction rate quantitatively and this dimensionless number can be applied to other ultrasonic bath with different condition.", "classifications": [ { "id": "Yamamoto", "label": "Group Yamamoto", "parent": "Toyoshima", "type": "group" }, { "id": "Toyoshima", "label": "Team Toyoshima", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Takuya", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Okino", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.ultsonch.2025.107361" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "40252561" } }, "mesh": [], "publication": { "conference_name": null, "date": "2025 Apr 17", "date_precision": "day", "issue": "", "normalized_date": "2025-04-17", "pages": "107361", "proceedings_title": null, "publisher": "", "title": "Ultrasonics sonochemistry", "volume": "117", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Does macroscopic mass transfer affect sonochemical reaction rate in an ultrasonic bath?", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Somatic DNMT3A R882 codon mutations drive the most common form of clonal haematopoiesis (CH) and are associated with increased acute myeloid leukaemia (AML) risk(1,2). Preventing expansion of DNMT3A-R882-mutant haematopoietic stem/progenitor cells (HSPCs) may therefore avert progression to AML. To identify DNMT3A-R882-mutant-specific vulnerabilities, we conducted a genome-wide CRISPR screen on primary mouse Dnmt3a(R882H/+) HSPCs. Amongst the 640 vulnerability genes identified, many were involved in mitochondrial metabolism and metabolic flux analysis confirmed enhanced oxidative phosphorylation usage in Dnmt3a(R882H/+) vs Dnmt3a(+/+) (WT) HSPCs. We selected citrate/malate transporter Slc25a1 and complex I component Ndufb11, for which pharmacological inhibitors are available, for downstream studies. In vivo administration of SLC25A1 inhibitor CTPI2 and complex I inhibitors IACS-010759 and metformin, suppressed post-transplantation clonal expansion of Dnmt3a(R882H/+), but not WT, LT-HSC. The effect of metformin was recapitulated using a primary human DNMT3A-R882 CH sample. Notably, analysis of 412,234 UK Biobank (UKB) participants revealed that individuals taking metformin had markedly lower prevalence of DNMT3A-R882-mutant CH, after controlling for potential confounders including glycated haemoglobin, diabetes and body mass index. Collectively, our data propose modulation of mitochondrial metabolism as a therapeutic strategy for prevention of DNMT3A-R882-mutant AML.", "classifications": [ { "id": "Yusa", "label": "Group Yusa", "parent": "Eiraku", "type": "group" }, { "id": "Eiraku", "label": "Team Eiraku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Malgorzata", "last_name": "Gozdecka", "name": null }, { "creator_type": "author", "first_name": "Monika", "last_name": "Dudek", "name": null }, { "creator_type": "author", "first_name": "Sean", "last_name": "Wen", "name": null }, { "creator_type": "author", "first_name": "Muxin", "last_name": "Gu", "name": null }, { "creator_type": "author", "first_name": "Richard J.", "last_name": "Stopforth", "name": null }, { "creator_type": "author", "first_name": "Justyna", "last_name": "Rak", "name": null }, { "creator_type": "author", "first_name": "Aristi", "last_name": "Damaskou", "name": null }, { "creator_type": "author", "first_name": "Guinevere L.", "last_name": "Grice", "name": null }, { "creator_type": "author", "first_name": "Matthew A.", "last_name": "McLoughlin", "name": null }, { "creator_type": "author", "first_name": "Laura", "last_name": "Bond", "name": null }, { "creator_type": "author", "first_name": "Rachael", "last_name": "Wilson", "name": null }, { "creator_type": "author", "first_name": "George", "last_name": "Giotopoulos", "name": null }, { "creator_type": "author", "first_name": "Vijaya", "last_name": "Mahalingam Shanmugiah", "name": null }, { "creator_type": "author", "first_name": "Rula Bany", "last_name": "Bakar", "name": null }, { "creator_type": "author", "first_name": "Eliza", "last_name": "Yankova", "name": null }, { "creator_type": "author", "first_name": "Jonathan L.", "last_name": "Cooper", "name": null }, { "creator_type": "author", "first_name": "Nisha", "last_name": "Narayan", "name": null }, { "creator_type": "author", "first_name": "Sarah J.", "last_name": "Horton", "name": null }, { "creator_type": "author", "first_name": "Ryan", "last_name": "Asby", "name": null }, { "creator_type": "author", "first_name": "Dean C.", "last_name": "Pask", "name": null }, { "creator_type": "author", "first_name": "Annalisa", "last_name": "Mupo", "name": null }, { "creator_type": "author", "first_name": "Graham", "last_name": "Duddy", "name": null }, { "creator_type": "author", "first_name": "Ludovica", "last_name": "Marando", "name": null }, { "creator_type": "author", "first_name": "Theodoros", "last_name": "Georgomanolis", "name": null }, { "creator_type": "author", "first_name": "Paul", "last_name": "Carter", "name": null }, { "creator_type": "author", "first_name": "Amirtha Priya", "last_name": "Ramesh", "name": null }, { "creator_type": "author", "first_name": "William G.", "last_name": "Dunn", "name": null }, { "creator_type": "author", "first_name": "Clea", "last_name": "Barcena", "name": null }, { "creator_type": "author", "first_name": "Paolo", "last_name": "Gallipoli", "name": null }, { "creator_type": "author", "first_name": "Kosuke", "last_name": "Yusa", "name": null }, { "creator_type": "author", "first_name": "Slave", "last_name": "Petrovski", "name": null }, { "creator_type": "author", "first_name": "Penny", "last_name": "Wright", "name": null }, { "creator_type": "author", "first_name": "Pedro M.", "last_name": "Quiros", "name": null }, { "creator_type": "author", "first_name": "Christian", "last_name": "Frezza", "name": null }, { "creator_type": "author", "first_name": "James A.", "last_name": "Nathan", "name": null }, { "creator_type": "author", "first_name": "Arthur", "last_name": "Kaser", "name": null }, { "creator_type": "author", "first_name": "Siddhartha", "last_name": "Kar", "name": null }, { "creator_type": "author", "first_name": "Konstantinos", "last_name": "Tzelepis", "name": null }, { "creator_type": "author", "first_name": "Jonathan", "last_name": "Mitchell", "name": null }, { "creator_type": "author", "first_name": "Margarete A.", "last_name": "Fabre", "name": null }, { "creator_type": "author", "first_name": "Brian J. P.", "last_name": "Huntly", "name": null }, { "creator_type": "author", "first_name": "George S.", "last_name": "Vassiliou", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41586-025-08980-6" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "40239706" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Clonal Hematopoiesis", "descriptor_ui": "D000082182", "major_topic": true }, { "descriptor": "Clone Cells", "descriptor_ui": "D002999", "major_topic": false }, { "descriptor": "DNA (Cytosine-5-)-Methyltransferases", "descriptor_ui": "D004248", "major_topic": true }, { "descriptor": "DNA Methyltransferase 3A", "descriptor_ui": "D000090205", "major_topic": false }, { "descriptor": "Electron Transport Complex I", "descriptor_ui": "D042967", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Hematopoietic Stem Cells", "descriptor_ui": "D006412", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Leukemia, Myeloid, Acute", "descriptor_ui": "D015470", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Metformin", "descriptor_ui": "D008687", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mitochondria", "descriptor_ui": "D008928", "major_topic": true }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": true }, { "descriptor": "Oxidative Phosphorylation", "descriptor_ui": "D010085", "major_topic": false } ], "publication": { "conference_name": null, "date": "2025 Apr 16", "date_precision": "day", "issue": "", "normalized_date": "2025-04-16", "pages": "", "proceedings_title": null, "publisher": "", "title": "Nature", "volume": "", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Mitochondrial metabolism sustains DNMT3A-R882-mutant clonal haematopoiesis.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "INTRODUCTION: Neoadjuvant chemo-immunotherapy is one of the standard treatment options for resectable stage II-III non-small cell lung cancer (NSCLC). However, this treatment yielded insufficient local control in the CheckMate 816 trial. We hypothesized that adding radiotherapy could improve local control, thereby improving survival outcomes. METHODS: Eligible patients had clinical T1-3/T4 (tumor size) N2 stage IIIA-B NSCLC (AJCC ver. 8), pathologically confirmed as N2 without extranodal invasion. Patients received concurrent chemoradiotherapy (carboplatin [AUC 2] and paclitaxel [40 mg/ml] on days 1, 8, 15, 22, and 29, with 50 Gy radiation over 25 days) and durvalumab [1500 mg] on days 1 and 29, followed by surgical resection within 2-6 weeks. After surgery, durvalumab adjuvant therapy was administered for up to 1 year. The primary endpoint was major pathologic response (MPR: 0.80) and moderate criterion validity. DISCUSSION: The findings provide further evidence of the reliability and validity of the BEDS-7 as a potential screening tool for identifying probable cases of BED globally, facilitating early intervention in primary care settings.", "classifications": [ { "id": "Fujiwara", "label": "Group Fujiwara", "parent": "Fujiwara", "type": "group" }, { "id": "Fujiwara", "label": "Team Fujiwara", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Ateret", "last_name": "Gewirtz-Meydan", "name": null }, { "creator_type": "author", "first_name": "Zohar", "last_name": "Spivak-Lavi", "name": null }, { "creator_type": "author", "first_name": "Shane W.", "last_name": "Kraus", "name": null }, { "creator_type": "author", "first_name": "Lena", "last_name": "Nagy", "name": null }, { "creator_type": "author", "first_name": "Monika", "last_name": "Koos", "name": null }, { "creator_type": "author", "first_name": "Zsolt", "last_name": "Demetrovics", "name": null }, { "creator_type": "author", "first_name": "Marc N.", "last_name": "Potenza", "name": null }, { "creator_type": "author", "first_name": "Rafael", "last_name": "Ballester-Arnal", "name": null }, { "creator_type": "author", "first_name": "Dominik", "last_name": "Batthyany", "name": null }, { "creator_type": "author", "first_name": "Sophie", "last_name": "Bergeron", "name": null }, { "creator_type": "author", "first_name": "Joel", "last_name": "Billieux", "name": null }, { "creator_type": "author", "first_name": "Peer", "last_name": "Briken", "name": null }, { "creator_type": "author", "first_name": "Julius", "last_name": "Burkauskas", "name": null }, { "creator_type": "author", "first_name": "Georgina", "last_name": "Cardenas-Lopez", "name": null }, { "creator_type": "author", "first_name": "Joana", "last_name": "Carvalho", "name": null }, { "creator_type": "author", "first_name": "Jesus", "last_name": "Castro-Calvo", "name": null }, { "creator_type": "author", "first_name": "Lijun", "last_name": "Chen", "name": null }, { "creator_type": "author", "first_name": "Giacomo", "last_name": "Ciocca", "name": null }, { "creator_type": "author", "first_name": "Ornella", "last_name": "Corazza", "name": null }, { "creator_type": "author", "first_name": "Rita I.", "last_name": "Csako", "name": null }, { "creator_type": "author", "first_name": "David P.", "last_name": "Fernandez", "name": null }, { "creator_type": "author", "first_name": "Elaine F.", "last_name": "Fernandez", "name": null }, { "creator_type": "author", "first_name": "Hironobu", "last_name": "Fujiwara", "name": null }, { "creator_type": "author", "first_name": "Johannes", "last_name": "Fuss", "name": null }, { "creator_type": "author", "first_name": "Roman", "last_name": "Gabrhelik", "name": null }, { "creator_type": "author", "first_name": "Biljana", "last_name": "Gjoneska", "name": null }, { "creator_type": "author", "first_name": "Mateusz", "last_name": "Gola", "name": null }, { "creator_type": "author", "first_name": "Joshua B.", "last_name": "Grubbs", "name": null }, { "creator_type": "author", "first_name": "Hashim T.", "last_name": "Hashim", "name": null }, { "creator_type": "author", "first_name": "Md Saiful", "last_name": "Islam", "name": null }, { "creator_type": "author", "first_name": "Mustafa", "last_name": "Ismail", "name": null }, { "creator_type": "author", "first_name": "Martha C.", "last_name": "Jimenez-Martinez", "name": null }, { "creator_type": "author", "first_name": "Tanja", "last_name": "Jurin", "name": null }, { "creator_type": "author", "first_name": "Ondrej", "last_name": "Kalina", "name": null }, { "creator_type": "author", "first_name": "Verena", "last_name": "Klein", "name": null }, { "creator_type": "author", "first_name": "Andras", "last_name": "Kolto", "name": null }, { "creator_type": "author", "first_name": "Chih-Ting", "last_name": "Lee", "name": null }, { "creator_type": "author", "first_name": "Sang-Kyu", "last_name": "Lee", "name": null }, { "creator_type": "author", "first_name": "Karol", "last_name": "Lewczuk", "name": null }, { "creator_type": "author", "first_name": "Chung-Ying", "last_name": "Lin", "name": null }, { "creator_type": "author", "first_name": "Christine", "last_name": "Lochner", "name": null }, { "creator_type": "author", "first_name": "Silvia", "last_name": "Lopez-Alvarado", "name": null }, { "creator_type": "author", "first_name": "Katerina", "last_name": "Lukavska", "name": null }, { "creator_type": "author", "first_name": "Percy", "last_name": "Mayta-Tristan", "name": null }, { "creator_type": "author", "first_name": "Dan J.", "last_name": "Miller", "name": null }, { "creator_type": "author", "first_name": "Olga", "last_name": "Orosova", "name": null }, { "creator_type": "author", "first_name": "Gabor", "last_name": "Orosz", "name": null }, { "creator_type": "author", "first_name": "Hyein", "last_name": "Chang", "name": null }, { "creator_type": "author", "first_name": "Kyeongwoo", "last_name": "Park", "name": null }, { "creator_type": "author", "first_name": "Fernando P.", "last_name": "Ponce", "name": null }, { "creator_type": "author", "first_name": "Gonzalo R.", "last_name": "Quintana", "name": null }, { "creator_type": "author", "first_name": "Gabriel C.", "last_name": "Quintero Garzola", "name": null }, { "creator_type": "author", "first_name": "Jano", "last_name": "Ramos-Diaz", "name": null }, { "creator_type": "author", "first_name": "Kevin", "last_name": "Rigaud", "name": null }, { "creator_type": "author", "first_name": "Ann", "last_name": "Rousseau", "name": null }, { "creator_type": "author", "first_name": "Marco De Tubino", "last_name": "Scanavino", "name": null }, { "creator_type": "author", "first_name": "Marion K.", "last_name": "Schulmeyer", "name": null }, { "creator_type": "author", "first_name": "Pratap", "last_name": "Sharan", "name": null }, { "creator_type": "author", "first_name": "Mami", "last_name": "Shibata", "name": null }, { "creator_type": "author", "first_name": "Sheikh", "last_name": "Shoib", "name": null }, { "creator_type": "author", "first_name": "Vera", "last_name": "Sigre-Leiros", "name": null }, { "creator_type": "author", "first_name": "Luke", "last_name": "Sniewski", "name": null }, { "creator_type": "author", "first_name": "Ognen", "last_name": "Spasovski", "name": null }, { "creator_type": "author", "first_name": "Vesta", "last_name": "Steibliene", "name": null }, { "creator_type": "author", "first_name": "Dan J.", "last_name": "Stein", "name": null }, { "creator_type": "author", "first_name": "Julian", "last_name": "Strizek", "name": null }, { "creator_type": "author", "first_name": "Berk C.", "last_name": "Unsal", "name": null }, { "creator_type": "author", "first_name": "Marie-Pier", "last_name": "Vaillancourt-Morel", "name": null }, { "creator_type": "author", "first_name": "Marie Claire", "last_name": "Van Hout", "name": null }, { "creator_type": "author", "first_name": "Beata", "last_name": "Bothe", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/eat.24365" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "40040591" } }, "mesh": [ { "descriptor": "Adolescent", "descriptor_ui": "D000293", "major_topic": false }, { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Binge-Eating Disorder", "descriptor_ui": "D056912", "major_topic": true }, { "descriptor": "Cross-Cultural Comparison", "descriptor_ui": "D003431", "major_topic": true }, { "descriptor": "Cross-Sectional Studies", "descriptor_ui": "D003430", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Psychiatric Status Rating Scales", "descriptor_ui": "D011569", "major_topic": true }, { "descriptor": "Psychometrics", "descriptor_ui": "D011594", "major_topic": false }, { "descriptor": "Reproducibility of Results", "descriptor_ui": "D015203", "major_topic": false }, { "descriptor": "Surveys and Questionnaires", "descriptor_ui": "D011795", "major_topic": false }, { "descriptor": "Young Adult", "descriptor_ui": "D055815", "major_topic": false } ], "publication": { "conference_name": null, "date": "2025 Mar 5", "date_precision": "day", "issue": "", "normalized_date": "2025-03-05", "pages": "", "proceedings_title": null, "publisher": "", "title": "The International journal of eating disorders", "volume": "", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Cross-Cultural Validation of the Binge Eating Disorder Screener-7 (BEDS-7) Across 42 Countries.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The liver is the most lethal metastatic site in castration-resistant prostate cancer (CRPC). Overexpression of MET protein has been reported in CRPC, and MET is an important driver gene in androgen-independent CRPC cells. Mouse CRPC cell line CRTC2 was established by subcutaneous injection of hormone-sensitive PC cells (TRAMP-C2) in castrated nude mice. CRCT2/luc2 cells were injected into the spleen of castrated nude mice, and liver metastasis was confirmed at 2 weeks post-injection. We administered MET inhibitor (MET-I) and HGF activator inhibitor (HGFA-I) to this liver metastasis model and assessed the therapeutic effect. After intrasplenic injection, CRTC2 showed a higher incidence of liver metastasis whereas no metastasis was observed in TRAMP-C2. Microarray analysis revealed increased expression of HGF, MET, and HPN, HGFAC (encoding HGF activating proteases) in liver metastasis. Proliferation of CRCT2 was significantly inhibited by co-administration of MET-I and HGFA-I by in vitro analysis with HGF-enriched condition. In an analysis of the mouse model, the combination-therapy group showed the strongest reduction for liver metastasis. Immunohistochemical staining also revealed the strongest decrease in phosphorylation of MET in the combination-therapy group. Co-culture with HGF-expressed mouse fibroblasts showed attenuation of the inhibitory effect of MET-I; however, additional HGFA-I overcame the resistance. We established an androgen-independent CRPC cell line, CRTC2, and liver metastasis model in mice. Significant effect was confirmed by combined treatment of MET-I and HGFA-I by in vitro and in vivo analysis. The results suggested the importance of combined treatment with both MET- and HGF-targeting agents in the treatment of HGF-enriched conditions including liver metastasis.", "classifications": [ { "id": "Kuchimaru", "label": "Group Kuchimaru", "parent": "Shintaku", "type": "group" }, { "id": "Shintaku", "label": "Team Shintaku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Shoichi", "last_name": "Kimura", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Iwano", "name": null }, { "creator_type": "author", "first_name": "Takahiro", "last_name": "Akioka", "name": null }, { "creator_type": "author", "first_name": "Takahiro", "last_name": "Kuchimaru", "name": null }, { "creator_type": "author", "first_name": "Makiko", "last_name": "Kawaguchi", "name": null }, { "creator_type": "author", "first_name": "Tsuyoshi", "last_name": "Fukushima", "name": null }, { "creator_type": "author", "first_name": "Yuichiro", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Hiroaki", "last_name": "Kataoka", "name": null }, { "creator_type": "author", "first_name": "Toshiyuki", "last_name": "Kamoto", "name": null }, { "creator_type": "author", "first_name": "Shoichiro", "last_name": "Mukai", "name": null }, { "creator_type": "author", "first_name": "Atsuro", "last_name": "Sawada", "name": null } ], "identifiers": { "doi": { "normalized": "10.3390/ijms26052308" }, "pmcid": { "normalized": "PMC11900290" }, "pmid": { "normalized": "40076928" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Cell Proliferation", "descriptor_ui": "D049109", "major_topic": false }, { "descriptor": "Hepatocyte Growth Factor", "descriptor_ui": "D017228", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Liver Neoplasms", "descriptor_ui": "D008113", "major_topic": true }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Nude", "descriptor_ui": "D008819", "major_topic": false }, { "descriptor": "Prostatic Neoplasms, Castration-Resistant", "descriptor_ui": "D064129", "major_topic": true }, { "descriptor": "Proto-Oncogene Proteins c-met", "descriptor_ui": "D019859", "major_topic": true }, { "descriptor": "Xenograft Model Antitumor Assays", "descriptor_ui": "D023041", "major_topic": false } ], "publication": { "conference_name": null, "date": "2025 Mar 5", "date_precision": "day", "issue": "5", "normalized_date": "2025-03-05", "pages": "", "proceedings_title": null, "publisher": "", "title": "International journal of molecular sciences", "volume": "26", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Combined Therapy Targeting MET and Pro-HGF Activation Shows Significant Therapeutic Effect Against Liver Metastasis of CRPC.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Isorhamnetin (ISO), a dietary flavonoid, has been shown to possess antioxidant, anti-cancer, and anti-inflammatory properties. Cancer-associated fibroblasts (CAFs), found in the tumor microenvironment of several types of cancer including pancreatic ductal adenocarcinoma (PDAC) impact the tumor growth and development of chemoresistance. Thus, modulating CAFs is an attractive mean to increase the efficacy of therapies targeting cancer cells. In this study, the anti-proliferative effect of ISO and the underlying transcriptomic profile of ISO-treated PDAC-derived CAFs were investigated. ISO treatment showed a time- and concentration-dependent decrease in cell viability with a slight increase in apoptotic cells. Microarray and cell cycle analyses revealed ISO induced downregulation of pathways in cell cycle and DNA replication; and G2/M checkpoint. Cell cycle analysis showed cells in the G2/M phase were increased. In response to the treatment, hallmark for p53 pathway genes, known to regulate cell cycle checkpoints, were highly upregulated. Moreover, ISO-treated cells had an increased area of the mitochondrial network, but lower mitochondrial membrane potential accompanied by a decrease of ATP production, measured by oxygen consumption rate. Inflammatory gene expression of IL1A1, IL6, CXCL1, and LIF were significantly inhibited in ISO-treated CAFs. Taken together, our results demonstrated that the cytostatic effect of ISO on human CAFs was mediated by inducing cell cycle arrest at G2/M phase associated with activation of p21, impaired mitochondrial homeostasis, and inhibition of inflammatory mediators gene expression, warranting further investigation for its use in combinatorial therapy that target both the cancer and the tumor microenvironment as a whole.", "classifications": [ { "id": "Miyamoto", "label": "Group Miyamoto", "parent": "Wakamoto", "type": "group" }, { "id": "Wakamoto", "label": "Team Wakamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Munkhzul", "last_name": "Ganbold", "name": null }, { "creator_type": "author", "first_name": "Pakavarin", "last_name": "Louphrasitthiphol", "name": null }, { "creator_type": "author", "first_name": "Takafumi", "last_name": "Miyamoto", "name": null }, { "creator_type": "author", "first_name": "Yoshihiro", "last_name": "Miyazaki", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Oda", "name": null }, { "creator_type": "author", "first_name": "Kenichi", "last_name": "Tominaga", "name": null }, { "creator_type": "author", "first_name": "Hiroko", "last_name": "Isoda", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.biopha.2025.117954" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "40031374" } }, "mesh": [ { "descriptor": "Apoptosis", "descriptor_ui": "D017209", "major_topic": false }, { "descriptor": "Cancer-Associated Fibroblasts", "descriptor_ui": "D000072645", "major_topic": true }, { "descriptor": "Carcinoma, Pancreatic Ductal", "descriptor_ui": "D021441", "major_topic": true }, { "descriptor": "Cell Cycle Checkpoints", "descriptor_ui": "D059447", "major_topic": true }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Cell Proliferation", "descriptor_ui": "D049109", "major_topic": true }, { "descriptor": "Cell Survival", "descriptor_ui": "D002470", "major_topic": false }, { "descriptor": "Gene Expression Regulation, Neoplastic", "descriptor_ui": "D015972", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Membrane Potential, Mitochondrial", "descriptor_ui": "D053078", "major_topic": false }, { "descriptor": "Pancreatic Neoplasms", "descriptor_ui": "D010190", "major_topic": true }, { "descriptor": "Quercetin", "descriptor_ui": "D011794", "major_topic": true }, { "descriptor": "Tumor Microenvironment", "descriptor_ui": "D059016", "major_topic": false } ], "publication": { "conference_name": null, "date": "2025 Mar 2", "date_precision": "day", "issue": "", "normalized_date": "2025-03-02", "pages": "117954", "proceedings_title": null, "publisher": "", "title": "Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie", "volume": "185", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Isorhamnetin exerts anti-proliferative effect on cancer-associated fibroblasts by inducing cell cycle arrest.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Transient memories are converted to persistent memories at the synapse and circuit/systems levels. The synapse-level consolidation parallels electrophysiological transition from early- to late-phase long-term potentiation of synaptic transmission (E-/L-LTP). While glutamate signaling upregulations coupled with dendritic spine enlargement are common underpinnings of E-LTP and L-LTP, synaptic mechanisms conferring persistence on L-LTP remain unclear. Here, we show that L-LTP induced at the perforant path-hippocampal dentate gyrus (DG) synapses accompanies cytoskeletal remodeling that involves actin and the septin subunit SEPT3. L-LTP in DG neurons causes fast spine enlargement, followed by SEPT3-dependent smooth endoplasmic reticulum (sER) extension into enlarged spines. Spines containing sER show greater Ca(2+) responses upon synaptic input and local synaptic activity. Consistently, Sept3 knockout in mice (Sept3(-/-)) impairs memory consolidation and causes a scarcity of sER-containing spines. These findings indicate a concept that sER extension into active spines serves as a synaptic basis of memory consolidation.", "classifications": [ { "id": "Sato", "label": "Group Sato", "parent": "Tsuchiya", "type": "group" }, { "id": "Tsuchiya", "label": "Team Tsuchiya", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Natsumi", "last_name": "Ageta-Ishihara", "name": null }, { "creator_type": "author", "first_name": "Yugo", "last_name": "Fukazawa", "name": null }, { "creator_type": "author", "first_name": "Fumiko", "last_name": "Arima-Yoshida", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Okuno", "name": null }, { "creator_type": "author", "first_name": "Yuichiro", "last_name": "Ishii", "name": null }, { "creator_type": "author", "first_name": "Keizo", "last_name": "Takao", "name": null }, { "creator_type": "author", "first_name": "Kohtarou", "last_name": "Konno", "name": null }, { "creator_type": "author", "first_name": "Kazuto", "last_name": "Fujishima", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Ageta", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Hioki", "name": null }, { "creator_type": "author", "first_name": "Kunihiro", "last_name": "Tsuchida", "name": null }, { "creator_type": "author", "first_name": "Yoshikatsu", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Mineko", "last_name": "Kengaku", "name": null }, { "creator_type": "author", "first_name": "Masahiko", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Ayako M.", "last_name": "Watabe", "name": null }, { "creator_type": "author", "first_name": "Toshiya", "last_name": "Manabe", "name": null }, { "creator_type": "author", "first_name": "Tsuyoshi", "last_name": "Miyakawa", "name": null }, { "creator_type": "author", "first_name": "Kaoru", "last_name": "Inokuchi", "name": null }, { "creator_type": "author", "first_name": "Haruhiko", "last_name": "Bito", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Kinoshita", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.celrep.2025.115352" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "40023151" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Dendritic Spines", "descriptor_ui": "D049229", "major_topic": true }, { "descriptor": "Dentate Gyrus", "descriptor_ui": "D018891", "major_topic": false }, { "descriptor": "Endoplasmic Reticulum", "descriptor_ui": "D004721", "major_topic": true }, { "descriptor": "Long-Term Potentiation", "descriptor_ui": "D017774", "major_topic": true }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Memory", "descriptor_ui": "D008568", "major_topic": true }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Septins", "descriptor_ui": "D058112", "major_topic": true }, { "descriptor": "Synapses", "descriptor_ui": "D013569", "major_topic": false }, { "descriptor": "Synaptic Transmission", "descriptor_ui": "D009435", "major_topic": false } ], "publication": { "conference_name": null, "date": "2025 Feb 27", "date_precision": "day", "issue": "", "normalized_date": "2025-02-27", "pages": "115352", "proceedings_title": null, "publisher": "", "title": "Cell reports", "volume": "", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Septin 3 regulates memory and L-LTP-dependent extension of endoplasmic reticulum into spines.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The ability of parasitic plants to withdraw nutrients from their hosts depends on the formation of an infective structure known as the haustorium. How parasites regulate their haustoria numbers is poorly understood, and here, we uncovered that existing haustoria in the facultative parasitic plants Phtheirospermum japonicum and Parentucellia viscosa suppressed the formation of new haustoria located on distant roots. Using Phtheirospermum, we found that this effect depended on the formation of mature haustoria and could be induced through the application of external nutrients. To understand the molecular basis of this root plasticity, we analyzed hormone response and found that existing infections upregulated cytokinin-responsive genes first at the haustoria and then more distantly in Phtheirospermum shoots. We observed that infections increased endogenous cytokinin levels in Phtheirospermum roots and shoots, and this increase appeared relevant since local treatments with exogenous cytokinins blocked the formation of both locally and distantly formed haustoria. In addition, local overexpression of a cytokinin-degrading enzyme in Phtheirospermum prevented this systemic interhaustoria repression and increased haustoria numbers locally. We propose that a long-distance signal produced by haustoria negatively regulates future haustoria, and in Phtheirospermum, such a signaling system is mediated by a local increase in cytokinin to regulate haustoria numbers and balance nutrient acquisition.", "classifications": [ { "id": "JPMJCR1924", "label": "JPMJCR1924", "researcher": "Yuichiro Tsuchiya", "type": "grant" }, { "id": "Tsuchiya", "label": "Group Tsuchiya", "parent": "Tsuchiya", "type": "group" }, { "id": "Tsuchiya", "label": "Team Tsuchiya", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Anna", "last_name": "Kokla", "name": null }, { "creator_type": "author", "first_name": "Martina", "last_name": "Leso", "name": null }, { "creator_type": "author", "first_name": "Jan", "last_name": "Simura", "name": null }, { "creator_type": "author", "first_name": "Cecilia", "last_name": "Wardig", "name": null }, { "creator_type": "author", "first_name": "Marina", "last_name": "Hayashi", "name": null }, { "creator_type": "author", "first_name": "Naoshi", "last_name": "Nishii", "name": null }, { "creator_type": "author", "first_name": "Yuichiro", "last_name": "Tsuchiya", "name": null }, { "creator_type": "author", "first_name": "Karin", "last_name": "Ljung", "name": null }, { "creator_type": "author", "first_name": "Charles W.", "last_name": "Melnyk", "name": null } ], "identifiers": { "doi": { "normalized": "10.1073/pnas.2424557122" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "39964721" } }, "mesh": [ { "descriptor": "Cytokinins", "descriptor_ui": "D003583", "major_topic": false }, { "descriptor": "Gene Expression Regulation, Plant", "descriptor_ui": "D018506", "major_topic": false }, { "descriptor": "Host-Parasite Interactions", "descriptor_ui": "D006790", "major_topic": true }, { "descriptor": "Orobanchaceae", "descriptor_ui": "D031670", "major_topic": true }, { "descriptor": "Plant Growth Regulators", "descriptor_ui": "D010937", "major_topic": false }, { "descriptor": "Plant Roots", "descriptor_ui": "D018517", "major_topic": false }, { "descriptor": "Plant Shoots", "descriptor_ui": "D018520", "major_topic": false } ], "publication": { "conference_name": null, "date": "2025 Feb 25", "date_precision": "day", "issue": "8", "normalized_date": "2025-02-25", "pages": "e2424557122", "proceedings_title": null, "publisher": "", "title": "Proceedings of the National Academy of Sciences of the United States of America", "volume": "122", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "A long-distance inhibitory system regulates haustoria numbers in parasitic plants.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Plants induce the expression of the florigen FLOWERING LOCUS T (FT) in response to seasonal changes. FT is expressed in a distinct subset of phloem companion cells in Arabidopsis. Using tissue-specific translatome analysis, we discovered that the FT-expressing cells also express FLOWERING PROMOTING FACTOR 1 (FPF1)-LIKE PROTEIN 1 (FLP1), specifically under long-day conditions with the red/far-red ratio of natural sunlight. The master regulator of FT, CONSTANS (CO), is essential for FLP1 expression, suggesting that FLP1 is involved in the photoperiod pathway. We show that FLP1 promotes early flowering independently of FT, is active in the shoot apical meristem, and induces the expression of SEPALLATA3 (SEP3), a key E-class homeotic gene. Unlike FT, FLP1 also facilitates inflorescence stem elongation. Our cumulative evidence suggests that the small FLP1 protein acts as a mobile signal like FT. Taken together, FLP1 accelerates flowering in parallel with FT and orchestrates flowering and stem elongation during the reproductive transition.", "classifications": [ { "id": "Sato", "label": "Group Sato", "parent": "Tsuchiya", "type": "group" }, { "id": "Tsuchiya", "label": "Team Tsuchiya", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Takagi", "name": null }, { "creator_type": "author", "first_name": "Nayoung", "last_name": "Lee", "name": null }, { "creator_type": "author", "first_name": "Andrew K.", "last_name": "Hempton", "name": null }, { "creator_type": "author", "first_name": "Savita", "last_name": "Purushwani", "name": null }, { "creator_type": "author", "first_name": "Michitaka", "last_name": "Notaguchi", "name": null }, { "creator_type": "author", "first_name": "Kota", "last_name": "Yamauchi", "name": null }, { "creator_type": "author", "first_name": "Kazumasa", "last_name": "Shirai", "name": null }, { "creator_type": "author", "first_name": "Yaichi", "last_name": "Kawakatsu", "name": null }, { "creator_type": "author", "first_name": "Susumu", "last_name": "Uehara", "name": null }, { "creator_type": "author", "first_name": "William G.", "last_name": "Albers", "name": null }, { "creator_type": "author", "first_name": "Benjamin L. R.", "last_name": "Downing", "name": null }, { "creator_type": "author", "first_name": "Shogo", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Takamasa", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Takakazu", "last_name": "Matsuura", "name": null }, { "creator_type": "author", "first_name": "Izumi C.", "last_name": "Mori", "name": null }, { "creator_type": "author", "first_name": "Nobutaka", "last_name": "Mitsuda", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Kurihara", "name": null }, { "creator_type": "author", "first_name": "Tomonao", "last_name": "Matsushita", "name": null }, { "creator_type": "author", "first_name": "Young Hun", "last_name": "Song", "name": null }, { "creator_type": "author", "first_name": "Yoshikatsu", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Mika", "last_name": "Nomoto", "name": null }, { "creator_type": "author", "first_name": "Naoyuki", "last_name": "Uchida", "name": null }, { "creator_type": "author", "first_name": "Yasuomi", "last_name": "Tada", "name": null }, { "creator_type": "author", "first_name": "Kousuke", "last_name": "Hanada", "name": null }, { "creator_type": "author", "first_name": "Josh T.", "last_name": "Cuperus", "name": null }, { "creator_type": "author", "first_name": "Christine", "last_name": "Queitsch", "name": null }, { "creator_type": "author", "first_name": "Takato", "last_name": "Imaizumi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.devcel.2025.02.003" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "40020678" } }, "mesh": [ { "descriptor": "Arabidopsis", "descriptor_ui": "D017360", "major_topic": true }, { "descriptor": "Arabidopsis Proteins", "descriptor_ui": "D029681", "major_topic": true }, { "descriptor": "DNA-Binding Proteins", "descriptor_ui": "D004268", "major_topic": false }, { "descriptor": "Florigen", "descriptor_ui": "D060405", "major_topic": true }, { "descriptor": "Flowers", "descriptor_ui": "D035264", "major_topic": true }, { "descriptor": "Gene Expression Regulation, Plant", "descriptor_ui": "D018506", "major_topic": false }, { "descriptor": "Meristem", "descriptor_ui": "D018519", "major_topic": false }, { "descriptor": "Photoperiod", "descriptor_ui": "D017440", "major_topic": false }, { "descriptor": "Plant Stems", "descriptor_ui": "D018547", "major_topic": true }, { "descriptor": "Transcription Factors", "descriptor_ui": "D014157", "major_topic": false } ], "publication": { "conference_name": null, "date": "2025 Feb 25", "date_precision": "day", "issue": "", "normalized_date": "2025-02-25", "pages": "S1534-5807(25)00065-6", "proceedings_title": null, "publisher": "", "title": "Developmental cell", "volume": "", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Florigen-producing cells express FPF1-LIKE PROTEIN 1 to accelerate flowering and stem growth in Arabidopsis.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Reproduction poses a substantial burden, especially for mammalian females. Puberty onset serves as a vital checkpoint, regulated based on the body's energy state, to prevent inappropriate reproductive activity under malnutrition. However, the neural basis of this puberty checkpoint remains poorly understood. Here, we demonstrate that peripubertal malnutrition in female mice reduces the synchronous activity episodes of arcuate kisspeptin neurons, which are critical regulators of the gonadotropin axis. Improved dietary availability increased the frequency of this pulsatile activity, facilitating puberty onset. Using a viral-genetic approach, we show that the activity of agouti-related protein neurons in the arcuate nucleus, a hunger center, can bidirectionally regulate the pulsatile activity of kisspeptin neurons and follicular maturation in the ovaries. Collectively, a neural circuit connecting feeding to reproductive centers acts as an adjuster of the frequency of pulsatile kisspeptin neuron activity based on dietary availability, contributing to the neural basis of the puberty checkpoint.", "classifications": [ { "id": "Miyamichi", "label": "Group Miyamichi", "parent": "Enomoto", "type": "group" }, { "id": "Enomoto", "label": "Team Enomoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Teppei", "last_name": "Goto", "name": null }, { "creator_type": "author", "first_name": "Mitsue", "last_name": "Hagihara", "name": null }, { "creator_type": "author", "first_name": "Satsuki", "last_name": "Irie", "name": null }, { "creator_type": "author", "first_name": "Takaya", "last_name": "Abe", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Kiyonari", "name": null }, { "creator_type": "author", "first_name": "Kazunari", "last_name": "Miyamichi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.neuron.2025.01.015" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "39999843" } }, "mesh": [ { "descriptor": "Agouti-Related Protein", "descriptor_ui": "D054369", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Arcuate Nucleus of Hypothalamus", "descriptor_ui": "D001111", "major_topic": true }, { "descriptor": "Diet", "descriptor_ui": "D004032", "major_topic": true }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Hypothalamus", "descriptor_ui": "D007031", "major_topic": true }, { "descriptor": "Kisspeptins", "descriptor_ui": "D059648", "major_topic": false }, { "descriptor": "Malnutrition", "descriptor_ui": "D044342", "major_topic": true }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Transgenic", "descriptor_ui": "D008822", "major_topic": false }, { "descriptor": "Neural Pathways", "descriptor_ui": "D009434", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": true }, { "descriptor": "Sexual Maturation", "descriptor_ui": "D012741", "major_topic": true } ], "publication": { "conference_name": null, "date": "2025 Feb 24", "date_precision": "day", "issue": "", "normalized_date": "2025-02-24", "pages": "S0896-6273(25)00041-8", "proceedings_title": null, "publisher": "", "title": "Neuron", "volume": "", "year": 2025 }, "ssbd": { "database": [], "repository": [ "ssbd-repos-000374" ] }, "title": "Dietary availability acutely influences puberty onset via a hypothalamic neural circuit.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Gallbladder cancer (GBC) is a highly aggressive malignancy exhibiting a correlation between increased body mass index and increased risk of developing GBC. In obese individuals, the release of free fatty acids from the adipose tissue into the circulating blood is augmented. However, the role of oleic acid (OA), one of the most abundant monounsaturated fatty acids in the plasma, in GBC cell proliferation has not been determined. In this study, we investigated the effects of OA on the proliferation of GBC cells. We focused on the role of G protein-coupled receptor 120/free fatty acid receptor 4 (GPR120/FFAR4) and G protein-coupled receptor 40/free fatty acid receptor 1 (GPR40/FFAR1), which have a high affinity for long-chain fatty acids. OA significantly promoted the proliferation of human GBC cell lines (G-415 and GBC-SD) in vitro, with the highest increase observed at 200 muM OA. In vivo, OA-treated nude mice bearing G-415 xenografts exhibited enhanced tumor growth compared to controls. Immunohistochemical analysis revealed the expression of GPR120 and GPR40 in cultured GBC cells and patient tissues. OA-induced proliferation was mediated by GPR120, as evident from significantly reduced cell proliferation upon GPR120 silencing or inhibition, and no effect of GPR40 inhibition. Furthermore, OA-induced GPR120 activation enhanced ERK phosphorylation, implicating the GPR120/ERK signaling pathway in GBC cell growth. To our knowledge, this is the first study to elucidate the role of OA in GBC cell proliferation via GPR120, suggesting its potential as a therapeutic target for GBC treatment.", "classifications": [ { "id": "Tanaka", "label": "Group Tanaka", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yuki", "last_name": "Sawai", "name": null }, { "creator_type": "author", "first_name": "Michiyo", "last_name": "Hayakawa", "name": null }, { "creator_type": "author", "first_name": "Hiroaki", "last_name": "Yasuda", "name": null }, { "creator_type": "author", "first_name": "Ryuta", "last_name": "Nakao", "name": null }, { "creator_type": "author", "first_name": "Takehiro", "last_name": "Ogata", "name": null }, { "creator_type": "author", "first_name": "Akihiro", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Kentaro", "last_name": "Mochizuki", "name": null }, { "creator_type": "author", "first_name": "Tomoki", "last_name": "Takata", "name": null }, { "creator_type": "author", "first_name": "Hayato", "last_name": "Miyake", "name": null }, { "creator_type": "author", "first_name": "Yoshio", "last_name": "Sogame", "name": null }, { "creator_type": "author", "first_name": "Ryo", "last_name": "Morimura", "name": null }, { "creator_type": "author", "first_name": "Toshihiro", "last_name": "Kurahashi", "name": null }, { "creator_type": "author", "first_name": "Ping", "last_name": "Dai", "name": null }, { "creator_type": "author", "first_name": "Eiichi", "last_name": "Konishi", "name": null }, { "creator_type": "author", "first_name": "Yoshito", "last_name": "Itoh", "name": null }, { "creator_type": "author", "first_name": "Hideo", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Yoshinori", "last_name": "Harada", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.bbrc.2025.151530" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "40023990" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Cell Proliferation", "descriptor_ui": "D049109", "major_topic": false }, { "descriptor": "Gallbladder Neoplasms", "descriptor_ui": "D005706", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "MAP Kinase Signaling System", "descriptor_ui": "D020935", "major_topic": true }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred BALB C", "descriptor_ui": "D008807", "major_topic": false }, { "descriptor": "Mice, Nude", "descriptor_ui": "D008819", "major_topic": false }, { "descriptor": "Oleic Acid", "descriptor_ui": "D019301", "major_topic": true }, { "descriptor": "Receptors, G-Protein-Coupled", "descriptor_ui": "D043562", "major_topic": true } ], "publication": { "conference_name": null, "date": "2025 Feb 23", "date_precision": "day", "issue": "", "normalized_date": "2025-02-23", "pages": "151530", "proceedings_title": null, "publisher": "", "title": "Biochemical and biophysical research communications", "volume": "754", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Oleic acid enhances the proliferation of gallbladder cancer cells via the GPR120/ERK pathway.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Mitochondrial tRNA taurine modifications mediated by mitochondrial tRNA translation optimization 1 (Mto1) is essential for the mitochondrial protein translation. Mto1 deficiency was shown to induce proteostress in embryonic stem cells. A recent finding that a patient with MTO1 gene mutation showed severe anemia led us to hypothesize that Mto1 dysfunctions may result in defective erythropoiesis. Hematopoietic-specific Mto1 conditional knockout (cKO) mice were embryonic lethal and showed niche-independent defect in erythroblast proliferation and terminal differentiation. Mechanistically, mitochondrial oxidative phosphorylation complexes were severely impaired in the Mto1 cKO fetal liver, and this was followed by cytosolic iron accumulation. Overloaded cytosolic iron promoted heme biosynthesis, which induced an unfolded protein response (UPR) in Mto1 cKO erythroblasts. An iron chelator or UPR inhibitor rescued erythroid terminal differentiation in the Mto1 cKO fetal liver in vitro. This mitochondrial regulation of iron homeostasis revealed the indispensable role of mitochondrial tRNA modification in fetal hematopoiesis.", "classifications": [ { "id": "Akaike", "label": "Group Akaike", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Morishima", "name": null }, { "creator_type": "author", "first_name": "Md", "last_name": "Fakruddin", "name": null }, { "creator_type": "author", "first_name": "Yohei", "last_name": "Kanamori", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Masuda", "name": null }, { "creator_type": "author", "first_name": "Akiko", "last_name": "Ogawa", "name": null }, { "creator_type": "author", "first_name": "Yuxin", "last_name": "Wang", "name": null }, { "creator_type": "author", "first_name": "Vivien A. C.", "last_name": "Schoonenberg", "name": null }, { "creator_type": "author", "first_name": "Falk", "last_name": "Butter", "name": null }, { "creator_type": "author", "first_name": "Yuichiro", "last_name": "Arima", "name": null }, { "creator_type": "author", "first_name": "Takaaki", "last_name": "Akaike", "name": null }, { "creator_type": "author", "first_name": "Toshiro", "last_name": "Moroishi", "name": null }, { "creator_type": "author", "first_name": "Kazuhito", "last_name": "Tomizawa", "name": null }, { "creator_type": "author", "first_name": "Toshio", "last_name": "Suda", "name": null }, { "creator_type": "author", "first_name": "Fan-Yan", "last_name": "Wei", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Takizawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1126/sciadv.adu3011" }, "pmcid": { "normalized": "PMC11844735" }, "pmid": { "normalized": "39983002" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": true }, { "descriptor": "Erythroblasts", "descriptor_ui": "D004900", "major_topic": false }, { "descriptor": "Erythroid Cells", "descriptor_ui": "D041905", "major_topic": true }, { "descriptor": "Erythropoiesis", "descriptor_ui": "D004920", "major_topic": true }, { "descriptor": "Homeostasis", "descriptor_ui": "D006706", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Iron", "descriptor_ui": "D007501", "major_topic": true }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Mitochondria", "descriptor_ui": "D008928", "major_topic": true }, { "descriptor": "Mitochondrial Proteins", "descriptor_ui": "D024101", "major_topic": false }, { "descriptor": "Protein Biosynthesis", "descriptor_ui": "D014176", "major_topic": true }, { "descriptor": "RNA, Transfer", "descriptor_ui": "D012343", "major_topic": false }, { "descriptor": "Unfolded Protein Response", "descriptor_ui": "D056811", "major_topic": false } ], "publication": { "conference_name": null, "date": "2025 Feb 21", "date_precision": "day", "issue": "8", "normalized_date": "2025-02-21", "pages": "eadu3011", "proceedings_title": null, "publisher": "", "title": "Science advances", "volume": "11", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Mitochondrial translation regulates terminal erythroid differentiation by maintaining iron homeostasis.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: The clinical information housed within unstructured electronic health records (EHRs) has the potential to promote cancer research. The National Cancer Center Hospital (NCCH) is widely recognized as a leading institution for the treatment of thoracic malignancies in Japan. Information on medical treatment, particularly the characteristics of malignant tumors that occur in patients, tumor response evaluation, and adverse events, was compiled into the databases of each NCCH department from EHRs. However, there have been few opportunities for integrated analysis of data on both the hospital and research institute. METHODS: We developed a method for predicting tumor response evaluation and survival curves of drug therapy from the EHRs of lung cancer patients using natural language processing. First, we developed a rule-based algorithm to predict treatment duration using a dictionary of anticancer drugs and regimens used for lung cancer treatment. Thereafter, we applied supervised learning to radiology reports during each treatment period and constructed a classification model to predict the tumor response evaluation of anticancer drugs and date when the progressive disease (PD) was determined. The predicted response and PD date can be used to draw a survival curve for the progression-free survival. RESULTS: We used the EHRs of 716 lung cancer treatments at the NCCH and structured data of the cases as labels for the training and testing of supervised learning. The structured data were manually curated by physicians and CRCs. We investigated the results and performance of the proposed method. Individual predictions of tumor response evaluation and PD date were not extremely high. However, the final predicted survival curves were nearly similar to the actual survival curves. CONCLUSIONS: Although it is difficult to construct a fully automated system using our method, we believe that it achieves sufficient performance for supporting physicians and CRCs constructing the database and providing clinical information to help researchers find out a chance of clinical studies.", "classifications": [ { "id": "Hamamoto", "label": "Group Hamamoto", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Toshiki", "last_name": "Takeuchi", "name": null }, { "creator_type": "author", "first_name": "Hidehito", "last_name": "Horinouchi", "name": null }, { "creator_type": "author", "first_name": "Ken", "last_name": "Takasawa", "name": null }, { "creator_type": "author", "first_name": "Masami", "last_name": "Mukai", "name": null }, { "creator_type": "author", "first_name": "Ken", "last_name": "Masuda", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Shinno", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Okuma", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Goto", "name": null }, { "creator_type": "author", "first_name": "Noboru", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Yuichiro", "last_name": "Ohe", "name": null }, { "creator_type": "author", "first_name": "Mototaka", "last_name": "Miyake", "name": null }, { "creator_type": "author", "first_name": "Hirokazu", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Masahiko", "last_name": "Kusumoto", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Aoki", "name": null }, { "creator_type": "author", "first_name": "Kunihiro", "last_name": "Nishimura", "name": null }, { "creator_type": "author", "first_name": "Ryuji", "last_name": "Hamamoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1186/s12911-025-02928-6" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "39962486" } }, "mesh": [ { "descriptor": "Antineoplastic Agents", "descriptor_ui": "D000970", "major_topic": true }, { "descriptor": "Electronic Health Records", "descriptor_ui": "D057286", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Japan", "descriptor_ui": "D007564", "major_topic": false }, { "descriptor": "Lung Neoplasms", "descriptor_ui": "D008175", "major_topic": true }, { "descriptor": "Natural Language Processing", "descriptor_ui": "D009323", "major_topic": true }, { "descriptor": "Survival Analysis", "descriptor_ui": "D016019", "major_topic": false } ], "publication": { "conference_name": null, "date": "2025 Feb 17", "date_precision": "day", "issue": "1", "normalized_date": "2025-02-17", "pages": "85", "proceedings_title": null, "publisher": "", "title": "BMC medical informatics and decision making", "volume": "25", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "A series of natural language processing for predicting tumor response evaluation and survival curve from electronic health records.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Supersulfides are molecular species characterized by catenated sulfur moieties, including low-molecular-weight and protein-bound supersulfides. Emerging evidence suggests that these molecules, abundantly present in diverse organisms, play essential roles far beyond their chemical properties, such as functions in energy metabolism, protein stabilization, and antiviral defense. Recent studies highlight their regulatory effects on pattern-recognition receptors (PRRs) and associated signaling pathways-such as nucleotide oligomerization domain-like receptor signaling, toll-like receptor signaling, and type I interferon receptor signaling-critical for innate immunity and inflammatory responses. Dysregulation of these pathways is implicated in a heterogeneous group of autoinflammatory diseases, including inflammasomopathies, relopathies, and type I interferonopathies, respectively. Notably, both endogenous and synthetic supersulfide donors have recently shown promising inhibitory effects on PRR signaling, offering their potential as targeted therapies for managing autoinflammatory conditions. This review summarizes the fundamental biology of supersulfides and typical autoinflammatory diseases, focusing on their roles in innate immune and inflammatory responses, while exploring their therapeutic potential in these diseases.", "classifications": [ { "id": "JPMJCR2024", "label": "JPMJCR2024", "researcher": "Motohiro Nishida", "type": "grant" }, { "id": "Akaike", "label": "Group Akaike", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Group Nishida", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Tianli", "last_name": "Zhang", "name": null }, { "creator_type": "author", "first_name": "Touya", "last_name": "Toyomoto", "name": null }, { "creator_type": "author", "first_name": "Tomohiro", "last_name": "Sawa", "name": null }, { "creator_type": "author", "first_name": "Takaaki", "last_name": "Akaike", "name": null }, { "creator_type": "author", "first_name": "Tetsuro", "last_name": "Matsunaga", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/1348-0421.13205" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "39956868" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Autoimmune Diseases", "descriptor_ui": "D001327", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Immunity, Innate", "descriptor_ui": "D007113", "major_topic": false }, { "descriptor": "Inflammasomes", "descriptor_ui": "D058847", "major_topic": false }, { "descriptor": "Inflammation", "descriptor_ui": "D007249", "major_topic": true }, { "descriptor": "Receptors, Pattern Recognition", "descriptor_ui": "D051192", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Sulfides", "descriptor_ui": "D013440", "major_topic": true }, { "descriptor": "Toll-Like Receptors", "descriptor_ui": "D051193", "major_topic": false } ], "publication": { "conference_name": null, "date": "2025 Feb 16", "date_precision": "day", "issue": "", "normalized_date": "2025-02-16", "pages": "", "proceedings_title": null, "publisher": "", "title": "Microbiology and immunology", "volume": "", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Supersulfides: A Promising Therapeutic Approach for Autoinflammatory Diseases.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND AND AIMS: The Moral Incongruence Model of Pornography Use proposes that pornography-use-related problems may be present due to problematic pornography use (PPU) and/or moral disapproval (MD) of pornography use. Despite some supporting empirical evidence, no study has tested the presence of different pornography-use profiles based on individuals' behavioral dysregulation (i.e., PPU) and moral values concerning pornography use. The generalizability of previous findings to diverse populations has also been limited given the scarcity of studies conducted outside of Western countries. METHODS: Using data from the International Sex Survey (42 countries, N = 66,994; Mage = 32.16 years, SD = 12.27), we conducted latent profile analysis to identify pornography-use profiles based on individuals' frequency of use, MD, and PPU. The profiles were compared along a wide range of pornography-use-related, sexuality-related, and psychological correlates. RESULTS: Six pornography-use profiles were identified, including two increased risk groups (i.e., Increased risk of PPU without MD and Increased risk of PPU with some MD). Several factors differentiated between the increased risk vs. no/low risk profiles (e.g., relatedness satisfaction) as well as between the two increased risk profiles (e.g., religiosity). Apart from behavioral dysregulation, moral values concerning pornography use played an important role in distinguishing pornography-use profiles and demonstrated the importance of inquiring about MD when working with individuals with pornography-use-related problems. CONCLUSION: Findings also support recent calls for better-integrated sex therapy and sexual medicine perspectives into pornography-use-related problems research and care.", "classifications": [ { "id": "Fujiwara", "label": "Group Fujiwara", "parent": "Fujiwara", "type": "group" }, { "id": "Fujiwara", "label": "Team Fujiwara", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Beata", "last_name": "Bothe", "name": null }, { "creator_type": "author", "first_name": "Istvan", "last_name": "Toth-Kiraly", "name": null }, { "creator_type": "author", "first_name": "Nevena", "last_name": "Popova", "name": null }, { "creator_type": "author", "first_name": "Lena", "last_name": "Nagy", "name": null }, { "creator_type": "author", "first_name": "Monika", "last_name": "Koos", "name": null }, { "creator_type": "author", "first_name": "Zsolt", "last_name": "Demetrovics", "name": null }, { "creator_type": "author", "first_name": "Marc N.", "last_name": "Potenza", "name": null }, { "creator_type": "author", "first_name": "Shane W.", "last_name": "Kraus", "name": null }, { "creator_type": "author", "first_name": "Rafael", "last_name": "Ballester-Arnal", "name": null }, { "creator_type": "author", "first_name": "Dominik", "last_name": "Batthyany", "name": null }, { "creator_type": "author", "first_name": "Sophie", "last_name": "Bergeron", "name": null }, { "creator_type": "author", "first_name": "Joel", "last_name": "Billieux", "name": null }, { "creator_type": "author", "first_name": "Peer", "last_name": "Briken", "name": null }, { "creator_type": "author", "first_name": "Julius", "last_name": "Burkauskas", "name": null }, { "creator_type": "author", "first_name": "Georgina", "last_name": "Cardenas-Lopez", "name": null }, { "creator_type": "author", "first_name": "Joana", "last_name": "Carvalho", "name": null }, { "creator_type": "author", "first_name": "Jesus", "last_name": "Castro-Calvo", "name": null }, { "creator_type": "author", "first_name": "Lijun", "last_name": "Chen", "name": null }, { "creator_type": "author", "first_name": "Giacomo", "last_name": "Ciocca", "name": null }, { "creator_type": "author", "first_name": "Ornella", "last_name": "Corazza", "name": null }, { "creator_type": "author", "first_name": "Rita I.", "last_name": "Csako", "name": null }, { "creator_type": "author", "first_name": "Andrea", "last_name": "Czako", "name": null }, { "creator_type": "author", "first_name": "David P.", "last_name": "Fernandez", "name": null }, { "creator_type": "author", "first_name": "Elaine F.", "last_name": "Fernandez", "name": null }, { "creator_type": "author", "first_name": "Hironobu", "last_name": "Fujiwara", "name": null }, { "creator_type": "author", "first_name": "Johannes", "last_name": "Fuss", "name": null }, { "creator_type": "author", "first_name": "Roman", "last_name": "Gabrhelik", "name": null }, { "creator_type": "author", "first_name": "Ateret", "last_name": "Gewirtz-Meydan", "name": null }, { "creator_type": "author", "first_name": "Biljana", "last_name": "Gjoneska", "name": null }, { "creator_type": "author", "first_name": "Mateusz", "last_name": "Gola", "name": null }, { "creator_type": "author", "first_name": "Hashim T.", "last_name": "Hashim", "name": null }, { "creator_type": "author", "first_name": "Md Saiful", "last_name": "Islam", "name": null }, { "creator_type": "author", "first_name": "Mustafa", "last_name": "Ismail", "name": null }, { "creator_type": "author", "first_name": "Martha C.", "last_name": "Jimenez-Martinez", "name": null }, { "creator_type": "author", "first_name": "Tanja", "last_name": "Jurin", "name": null }, { "creator_type": "author", "first_name": "Ondrej", "last_name": "Kalina", "name": null }, { "creator_type": "author", "first_name": "Verena", "last_name": "Klein", "name": null }, { "creator_type": "author", "first_name": "Andras", "last_name": "Kolto", "name": null }, { "creator_type": "author", "first_name": "Chih-Ting", "last_name": "Lee", "name": null }, { "creator_type": "author", "first_name": "Sang-Kyu", "last_name": "Lee", "name": null }, { "creator_type": "author", "first_name": "Karol", "last_name": "Lewczuk", "name": null }, { "creator_type": "author", "first_name": "Chung-Ying", "last_name": "Lin", "name": null }, { "creator_type": "author", "first_name": "Christine", "last_name": "Lochner", "name": null }, { "creator_type": "author", "first_name": "Silvia", "last_name": "Lopez-Alvarado", "name": null }, { "creator_type": "author", "first_name": "Katerina", "last_name": "Lukavska", "name": null }, { "creator_type": "author", "first_name": "Percy", "last_name": "Mayta-Tristan", "name": null }, { "creator_type": "author", "first_name": "Dan J.", "last_name": "Miller", "name": null }, { "creator_type": "author", "first_name": "Olga", "last_name": "Orosova", "name": null }, { "creator_type": "author", "first_name": "Gabor", "last_name": "Orosz", "name": null }, { "creator_type": "author", "first_name": "Fernando P.", "last_name": "Ponce", "name": null }, { "creator_type": "author", "first_name": "Gonzalo R.", "last_name": "Quintana", "name": null }, { "creator_type": "author", "first_name": "Gabriel C.", "last_name": "Quintero Garzola", "name": null }, { "creator_type": "author", "first_name": "Jano", "last_name": "Ramos-Diaz", "name": null }, { "creator_type": "author", "first_name": "Kevin", "last_name": "Rigaud", "name": null }, { "creator_type": "author", "first_name": "Ann", "last_name": "Rousseau", "name": null }, { "creator_type": "author", "first_name": "Marco de Tubino", "last_name": "Scanavino", "name": null }, { "creator_type": "author", "first_name": "Marion K.", "last_name": "Schulmeyer", "name": null }, { "creator_type": "author", "first_name": "Pratap", "last_name": "Sharan", "name": null }, { "creator_type": "author", "first_name": "Mami", "last_name": "Shibata", "name": null }, { "creator_type": "author", "first_name": "Sheikh", "last_name": "Shoib", "name": null }, { "creator_type": "author", "first_name": "Vera", "last_name": "Sigre-Leiros", "name": null }, { "creator_type": "author", "first_name": "Luke", "last_name": "Sniewski", "name": null }, { "creator_type": "author", "first_name": "Ognen", "last_name": "Spasovski", "name": null }, { "creator_type": "author", "first_name": "Vesta", "last_name": "Steibliene", "name": null }, { "creator_type": "author", "first_name": "Dan J.", "last_name": "Stein", "name": null }, { "creator_type": "author", "first_name": "Aleksandar", "last_name": "Stulhofer", "name": null }, { "creator_type": "author", "first_name": "Berk C.", "last_name": "Unsal", "name": null }, { "creator_type": "author", "first_name": "Marie-Pier", "last_name": "Vaillancourt-Morel", "name": null }, { "creator_type": "author", "first_name": "Marie Claire", "last_name": "Van Hout", "name": null }, { "creator_type": "author", "first_name": "Joshua B.", "last_name": "Grubbs", "name": null } ], "identifiers": { "doi": { "normalized": "10.1556/2006.2024.00054" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "39945767" } }, "mesh": [ { "descriptor": "Adolescent", "descriptor_ui": "D000293", "major_topic": false }, { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Erotica", "descriptor_ui": "D004882", "major_topic": true }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Morals", "descriptor_ui": "D009014", "major_topic": true }, { "descriptor": "Sexual Behavior", "descriptor_ui": "D012725", "major_topic": true }, { "descriptor": "Young Adult", "descriptor_ui": "D055815", "major_topic": false } ], "publication": { "conference_name": null, "date": "2025 Feb 13", "date_precision": "day", "issue": "", "normalized_date": "2025-02-13", "pages": "", "proceedings_title": null, "publisher": "", "title": "Journal of behavioral addictions", "volume": "", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Identification and comprehensive characterization of moral disapproval and behavioral dysregulation-based pornography-use profiles across 42 countries.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Squamous cell carcinoma arising from mature teratoma (SCC-MT) is a rare ovarian malignancy. The detailed molecular pathology of SCC-MT is not well understood. Moreover, the prognosis of the patients remains poor because no standard treatment has been established. In this study, we performed single-nucleus RNA sequencing and spatial transcriptomics using clinical SCC-MT samples to identify novel therapeutic candidates. snRNA-seq revealed three epithelial cell clusters, of which one was significantly associated with epidermis and keratinocyte development. Moreover, spatial transcriptomics revealed that the epithelial-mesenchymal transition was significantly inhibited, and the MYC and E2F targets were significantly activated in cancer spots on specimen sections. We focused on KLF5, which was one of the upregulated genes in cancer cells, and performed a functional analysis using NOSCC-1, a cell line derived from an SCC-MT. KLF5 downregulation significantly decreased cell proliferation and increased apoptosis. Furthermore, we previously identified miR-145-5p as a downregulated miRNA in SCC-MT. We demonstrated that miR-145-5p overexpression attenuated cell proliferation and decreased KLF5 expression. In conclusion, through multi-omics analyses, we identified unique gene expression profiles of SCC-MT and determined a role for KLF5 in SCC-MT development. Therefore, KLF5-related factors may be novel therapeutic targets, and further studies are needed to improve the diagnosis and treatment of SCC-MT.", "classifications": [ { "id": "Okamoto", "label": "Group Okamoto", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Kosuke", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Akira", "last_name": "Yokoi", "name": null }, { "creator_type": "author", "first_name": "Hironori", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Tamauchi", "name": null }, { "creator_type": "author", "first_name": "Masami", "last_name": "Kitagawa", "name": null }, { "creator_type": "author", "first_name": "Eri", "last_name": "Inami", "name": null }, { "creator_type": "author", "first_name": "Jun", "last_name": "Nakayama", "name": null }, { "creator_type": "author", "first_name": "Yutaro", "last_name": "Mori", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Okamoto", "name": null }, { "creator_type": "author", "first_name": "Yutaka", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Tomoyasu", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Hiroaki", "last_name": "Kajiyama", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Yamamoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/cas.70022" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "39948701" } }, "mesh": [ { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Apoptosis", "descriptor_ui": "D017209", "major_topic": false }, { "descriptor": "Carcinoma, Squamous Cell", "descriptor_ui": "D002294", "major_topic": true }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Cell Proliferation", "descriptor_ui": "D049109", "major_topic": false }, { "descriptor": "Epithelial-Mesenchymal Transition", "descriptor_ui": "D058750", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Gene Expression Profiling", "descriptor_ui": "D020869", "major_topic": false }, { "descriptor": "Gene Expression Regulation, Neoplastic", "descriptor_ui": "D015972", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Kruppel-Like Transcription Factors", "descriptor_ui": "D051741", "major_topic": false }, { "descriptor": "MicroRNAs", "descriptor_ui": "D035683", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Ovarian Neoplasms", "descriptor_ui": "D010051", "major_topic": true }, { "descriptor": "Sequence Analysis, RNA", "descriptor_ui": "D017423", "major_topic": false }, { "descriptor": "Single-Cell Analysis", "descriptor_ui": "D059010", "major_topic": false }, { "descriptor": "Teratoma", "descriptor_ui": "D013724", "major_topic": true }, { "descriptor": "Transcriptome", "descriptor_ui": "D059467", "major_topic": true } ], "publication": { "conference_name": null, "date": "2025 Feb 13", "date_precision": "day", "issue": "", "normalized_date": "2025-02-13", "pages": "", "proceedings_title": null, "publisher": "", "title": "Cancer science", "volume": "", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Single-Nucleus RNA Sequencing and Spatial Transcriptomics for Squamous Cell Carcinoma Arising From Ovarian Mature Teratoma.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Reactive oxygen species (ROS) produced by mechanically stretching cardiomyocytes is a crucial mediator to increase contractile force in accordance with the Frank-Starling law. However, excessive ROS production leads to oxidative stress, contributing to myocardial atrophic remodeling and cellular damage. NADPH oxidase, the primary enzyme responsible for ROS production localized on the plasma membrane and organelle membranes, plays a key role in membrane-oriented ROS signaling. Two isoforms of NADPH oxidase, Nox2 (constitutive) and Nox4 (inducible), are predominantly expressed in cardiomyocytes, each playing unique roles in different contexts. Recent studies have revealed that Nox proteins form protein signaling complexes with transient receptor potential (TRP) channel proteins, amplifying ROS signaling in hearts. This review presents the putative mechanism of protein-protein interaction between TRP and Nox and their pathophysiological significance in hearts and discusses therapeutic strategies targeting TRP-Nox protein interactions for the treatment of heart failure.", "classifications": [ { "id": "Nishida", "label": "Group Nishida", "parent": "Nishida", "type": "group" }, { "id": "Nishimura", "label": "Group Nishimura", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Xinya", "last_name": "Mi", "name": null }, { "creator_type": "author", "first_name": "Di", "last_name": "Wu", "name": null }, { "creator_type": "author", "first_name": "Tomoya", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Yuri", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Akiyuki", "last_name": "Nishimura", "name": null }, { "creator_type": "author", "first_name": "Motohiro", "last_name": "Nishida", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.jjcc.2025.02.016" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "39954724" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Heart Diseases", "descriptor_ui": "D006331", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Myocytes, Cardiac", "descriptor_ui": "D032383", "major_topic": true }, { "descriptor": "NADPH Oxidase 2", "descriptor_ui": "D000074662", "major_topic": false }, { "descriptor": "NADPH Oxidases", "descriptor_ui": "D019255", "major_topic": false }, { "descriptor": "Oxidation-Reduction", "descriptor_ui": "D010084", "major_topic": false }, { "descriptor": "Oxidative Stress", "descriptor_ui": "D018384", "major_topic": false }, { "descriptor": "Reactive Oxygen Species", "descriptor_ui": "D017382", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Transient Receptor Potential Channels", "descriptor_ui": "D050051", "major_topic": true } ], "publication": { "conference_name": null, "date": "2025 Feb 13", "date_precision": "day", "issue": "", "normalized_date": "2025-02-13", "pages": "S0914-5087(25)00064-4", "proceedings_title": null, "publisher": "", "title": "Journal of cardiology", "volume": "", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "TRP channels in cardiac mechano-redox coupling and diseases.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Vascular smooth muscle cells (VSMCs) can dynamically change their phenotype between contractile and synthetic forms in response to environmental stress, which is pivotal in maintaining vascular homeostasis and mediating pathological remodeling of blood vessels. We previously reported that suppression of canonical transient receptor potential 6 (TRPC6) channel-mediated cation entry sustains VSMCs contractile phenotype and promotes the blood flow recovery after hindlimb ischemia in mice. We also reported that Zn(2+), a metal biomolecule mobilized by TRPC6 channel activation, exerts potential beneficial effects on cardiac contractility and remodeling. Therefore, we hypothesized that TRPC6-mediated Zn(2+) influx participates in phenotype switching of VSMCs and vascular remodeling. We established rat aortic smooth muscle cells (RAoSMCs) stably expressing wild type (WT) and Zn(2+) only impermeable TRPC6 (KYD) mutant. Although the resting phenotypes were similar in both RAoSMCs, pharmacological TRPC6 activation by PPZ2 prevented the transforming growth factor (TGF) beta-induced reduction in the intracellular Zn(2+) amount and contractile differentiation in RAoSMCs (WT), but failed to prevent them in RAoSMCs (KYD). There were no significant differences in TRPC6-dependent cation currents among all RAoSMCs pretreated with or without TGFbeta and/or PPZ2, suggesting that TRPC6 channels are functionally expressed in RAoSMCs regardless of their phenotype. Treatment of mice with PPZ2 attenuated the progression of vascular remodeling caused by chronic angiotensin II infusion. These results suggest that Zn(2+) influx through TRPC6 channels negatively regulates the TGFbeta-induced contractile differentiation of VSMCs and the progression of vascular remodeling in rodents.", "classifications": [ { "id": "JPMJCR2024", "label": "JPMJCR2024", "researcher": "Motohiro Nishida", "type": "grant" }, { "id": "Nishida", "label": "Group Nishida", "parent": "Nishida", "type": "group" }, { "id": "Nishimura", "label": "Group Nishimura", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Chenlin", "last_name": "Su", "name": null }, { "creator_type": "author", "first_name": "Xinya", "last_name": "Mi", "name": null }, { "creator_type": "author", "first_name": "Tomoya", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Yuri", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Akiyuki", "last_name": "Nishimura", "name": null }, { "creator_type": "author", "first_name": "Ryu", "last_name": "Nagata", "name": null }, { "creator_type": "author", "first_name": "Yasuo", "last_name": "Mori", "name": null }, { "creator_type": "author", "first_name": "Motohiro", "last_name": "Nishida", "name": null } ], "identifiers": { "doi": { "normalized": "10.3390/biom15020267" }, "pmcid": { "normalized": "PMC11853136" }, "pmid": { "normalized": "40001570" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": true }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Muscle Contraction", "descriptor_ui": "D009119", "major_topic": false }, { "descriptor": "Muscle, Smooth, Vascular", "descriptor_ui": "D009131", "major_topic": true }, { "descriptor": "Myocytes, Smooth Muscle", "descriptor_ui": "D032389", "major_topic": true }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Rats, Sprague-Dawley", "descriptor_ui": "D017207", "major_topic": false }, { "descriptor": "Transforming Growth Factor beta", "descriptor_ui": "D016212", "major_topic": false }, { "descriptor": "TRPC Cation Channels", "descriptor_ui": "D050052", "major_topic": false }, { "descriptor": "TRPC6 Cation Channel", "descriptor_ui": "D000074287", "major_topic": true }, { "descriptor": "Vascular Remodeling", "descriptor_ui": "D066253", "major_topic": false }, { "descriptor": "Zinc", "descriptor_ui": "D015032", "major_topic": true } ], "publication": { "conference_name": null, "date": "2025 Feb 12", "date_precision": "day", "issue": "2", "normalized_date": "2025-02-12", "pages": "", "proceedings_title": null, "publisher": "", "title": "Biomolecules", "volume": "15", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "TRPC6-Mediated Zn(2+) Influx Negatively Regulates Contractile Differentiation of Vascular Smooth Muscle Cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Through-space electrical conduction in paddlewheel-type homovalent dinuclear complexes remains poorly understood, despite the numerous reports on these complexes. Herein, the electrical conduction of new Ru2(II,II) complexes with 2-pyrenecarboxylate (pyrCOO-) ligands, [Ru2(pyrCOO)4X2]∙n(X) (where X = DMF (Ru-DMF), NMP (Ru-NMP), DMA (Ru-DMA)), was investigated. The dimensionality of pi-stacking interactions between discrete molecules in Ru-DMA is higher (two-dimensional) than in Ru-DMF and Ru-NMP (stair-like one-dimensional). Nevertheless, Ru-DMF, which contains a slight amount of organic radicals, exhibited the highest electrical conductivity. This suggests that the large overlap and high dimensionality of pi-stacking interactions among the complexes, along with a slight organic radical impurity, contribute to the increased electrical conductivity.", "classifications": [ { "id": "Hijikata", "label": "Group Hijikata", "parent": "Tsuchiya", "type": "group" }, { "id": "Tsuchiya", "label": "Team Tsuchiya", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Ren", "last_name": "Takaki", "name": null }, { "creator_type": "author", "first_name": "Hiroaki", "last_name": "Iguchi", "name": null }, { "creator_type": "author", "first_name": "Liyuan", "last_name": "Qu", "name": null }, { "creator_type": "author", "first_name": "Jenny", "last_name": "Pirillo", "name": null }, { "creator_type": "author", "first_name": "Shinpei", "last_name": "Kusaka", "name": null }, { "creator_type": "author", "first_name": "Yuh", "last_name": "Hijikata", "name": null }, { "creator_type": "author", "first_name": "Hisaaki", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Wakana", "last_name": "Matsuda", "name": null }, { "creator_type": "author", "first_name": "Shu", "last_name": "Seki", "name": null }, { "creator_type": "author", "first_name": "Ryotaro", "last_name": "Matsuda", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/asia.202401599" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "39936643" } }, "mesh": [], "publication": { "conference_name": null, "date": "2025 Feb 12", "date_precision": "day", "issue": "", "normalized_date": "2025-02-12", "pages": "e202401599", "proceedings_title": null, "publisher": "", "title": "Chemistry, an Asian journal", "volume": "", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Diruthenium(II,II) Complex Assemblies Showing Electrical Conduction via pi-Stacked 2-Pyrenecarboxylate Moiety.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND AND AIMS: Despite a growing body of research on pornography use among women, there is a lack of understanding of the problematic versus non-problematic nature. The current study aimed to investigate the relationship between women's motivations for pornography use and sexual wellbeing using a cross-sectional, self-report survey design among participants from 42 countries. METHODS: The total sample included 82,243 participants, of whom 46,874 (57.0%) identified as women and were analyzed. The participants' age averaged at M = 29.67 years, with a standard deviation of SD = 10.11. Participants were asked to complete a questionnaire assessing their motivations for pornography use, as well as measures of sexual functioning, sexual desire, and sexual satisfaction. RESULTS: Study results suggest that across cultures, women's motivations for pornography use are associated with their sexual wellbeing. Specifically, when women reported using pornography for their own pleasure or sexual curiosity, it was associated with fewer sexual functioning problems and higher sexual desire. Conversely, when women reported using pornography due to a lack of sexual satisfaction in their relationships, it was associated with more sexual functioning problems. DISCUSSION AND CONCLUSIONS: These findings highlight the need to consider the multifaceted nature of pornography use among women, including the usage motives, to fully understand associations with sexual wellbeing. Additionally, the study emphasizes the importance of conducting further research utilizing longitudinal designs, to establish the directionality between pornography use motivations and sexual wellbeing among women.", "classifications": [ { "id": "Fujiwara", "label": "Group Fujiwara", "parent": "Fujiwara", "type": "group" }, { "id": "Fujiwara", "label": "Team Fujiwara", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Ateret", "last_name": "Gewirtz-Meydan", "name": null }, { "creator_type": "author", "first_name": "Hagit", "last_name": "Feder", "name": null }, { "creator_type": "author", "first_name": "Lena", "last_name": "Nagy", "name": null }, { "creator_type": "author", "first_name": "Monika", "last_name": "Koos", "name": null }, { "creator_type": "author", "first_name": "Shane W.", "last_name": "Kraus", "name": null }, { "creator_type": "author", "first_name": "Zsolt", "last_name": "Demetrovics", "name": null }, { "creator_type": "author", "first_name": "Marc N.", "last_name": "Potenza", "name": null }, { "creator_type": "author", "first_name": "Rafael", "last_name": "Ballester-Arnal", "name": null }, { "creator_type": "author", "first_name": "Dominik", "last_name": "Batthyany", "name": null }, { "creator_type": "author", "first_name": "Sophie", "last_name": "Bergeron", "name": null }, { "creator_type": "author", "first_name": "Joel", "last_name": "Billieux", "name": null }, { "creator_type": "author", "first_name": "Peer", "last_name": "Briken", "name": null }, { "creator_type": "author", "first_name": "Julius", "last_name": "Burkauskas", "name": null }, { "creator_type": "author", "first_name": "Georgina", "last_name": "Cardenas-Lopez", "name": null }, { "creator_type": "author", "first_name": "Joana", "last_name": "Carvalho", "name": null }, { "creator_type": "author", "first_name": "Jesus", "last_name": "Castro-Calvo", "name": null }, { "creator_type": "author", "first_name": "Lijun", "last_name": "Chen", "name": null }, { "creator_type": "author", "first_name": "Giacomo", "last_name": "Ciocca", "name": null }, { "creator_type": "author", "first_name": "Ornella", "last_name": "Corazza", "name": null }, { "creator_type": "author", "first_name": "Rita I.", "last_name": "Csako", "name": null }, { "creator_type": "author", "first_name": "David P.", "last_name": "Fernandez", "name": null }, { "creator_type": "author", "first_name": "Elaine F.", "last_name": "Fernandez", "name": null }, { "creator_type": "author", "first_name": "Hironobu", "last_name": "Fujiwara", "name": null }, { "creator_type": "author", "first_name": "Johannes", "last_name": "Fuss", "name": null }, { "creator_type": "author", "first_name": "Roman", "last_name": "Gabrhelik", "name": null }, { "creator_type": "author", "first_name": "Biljana", "last_name": "Gjoneska", "name": null }, { "creator_type": "author", "first_name": "Mateusz", "last_name": "Gola", "name": null }, { "creator_type": "author", "first_name": "Joshua B.", "last_name": "Grubbs", "name": null }, { "creator_type": "author", "first_name": "Hashim T.", "last_name": "Hashim", "name": null }, { "creator_type": "author", "first_name": "Md Saiful", "last_name": "Islam", "name": null }, { "creator_type": "author", "first_name": "Mustafa", "last_name": "Ismail", "name": null }, { "creator_type": "author", "first_name": "Martha C.", "last_name": "Jimenez-Martinez", "name": null }, { "creator_type": "author", "first_name": "Tanja", "last_name": "Jurin", "name": null }, { "creator_type": "author", "first_name": "Ondrej", "last_name": "Kalina", "name": null }, { "creator_type": "author", "first_name": "Verena", "last_name": "Klein", "name": null }, { "creator_type": "author", "first_name": "Andras", "last_name": "Kolto", "name": null }, { "creator_type": "author", "first_name": "Chih-Ting", "last_name": "Lee", "name": null }, { "creator_type": "author", "first_name": "Sang-Kyu", "last_name": "Lee", "name": null }, { "creator_type": "author", "first_name": "Karol", "last_name": "Lewczuk", "name": null }, { "creator_type": "author", "first_name": "Chung-Ying", "last_name": "Lin", "name": null }, { "creator_type": "author", "first_name": "Christine", "last_name": "Lochner", "name": null }, { "creator_type": "author", "first_name": "Silvia", "last_name": "Lopez-Alvarado", "name": null }, { "creator_type": "author", "first_name": "Katerina", "last_name": "Lukavska", "name": null }, { "creator_type": "author", "first_name": "Percy", "last_name": "Mayta-Tristan", "name": null }, { "creator_type": "author", "first_name": "Dan J.", "last_name": "Miller", "name": null }, { "creator_type": "author", "first_name": "Olga", "last_name": "Orosova", "name": null }, { "creator_type": "author", "first_name": "Gabor", "last_name": "Orosz", "name": null }, { "creator_type": "author", "first_name": "Fernando P.", "last_name": "Ponce", "name": null }, { "creator_type": "author", "first_name": "Gonzalo R.", "last_name": "Quintana", "name": null }, { "creator_type": "author", "first_name": "Gabriel C.", "last_name": "Quintero Garzola", "name": null }, { "creator_type": "author", "first_name": "Jano", "last_name": "Ramos-Diaz", "name": null }, { "creator_type": "author", "first_name": "Kevin", "last_name": "Rigaud", "name": null }, { "creator_type": "author", "first_name": "Ann", "last_name": "Rousseau", "name": null }, { "creator_type": "author", "first_name": "Marco", "last_name": "De Tubino Scanavino", "name": null }, { "creator_type": "author", "first_name": "Marion K.", "last_name": "Schulmeyer", "name": null }, { "creator_type": "author", "first_name": "Pratap", "last_name": "Sharan", "name": null }, { "creator_type": "author", "first_name": "Mami", "last_name": "Shibata", "name": null }, { "creator_type": "author", "first_name": "Sheikh", "last_name": "Shoib", "name": null }, { "creator_type": "author", "first_name": "Vera", "last_name": "Sigre-Leiros", "name": null }, { "creator_type": "author", "first_name": "Luke", "last_name": "Sniewski", "name": null }, { "creator_type": "author", "first_name": "Ognen", "last_name": "Spasovski", "name": null }, { "creator_type": "author", "first_name": "Vesta", "last_name": "Steibliene", "name": null }, { "creator_type": "author", "first_name": "Dan J.", "last_name": "Stein", "name": null }, { "creator_type": "author", "first_name": "Julian", "last_name": "Strizek", "name": null }, { "creator_type": "author", "first_name": "Aleksandar", "last_name": "Stulhofer", "name": null }, { "creator_type": "author", "first_name": "Berk C.", "last_name": "Unsal", "name": null }, { "creator_type": "author", "first_name": "Marie-Pier", "last_name": "Vaillancourt-Morel", "name": null }, { "creator_type": "author", "first_name": "Marie Claire", "last_name": "Van Hout", "name": null }, { "creator_type": "author", "first_name": "Beata", "last_name": "Bothe", "name": null } ], "identifiers": { "doi": { "normalized": "10.1556/2006.2024.00040" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "39945771" } }, "mesh": [ { "descriptor": "Adolescent", "descriptor_ui": "D000293", "major_topic": false }, { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Cross-Sectional Studies", "descriptor_ui": "D003430", "major_topic": false }, { "descriptor": "Erotica", "descriptor_ui": "D004882", "major_topic": true }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Libido", "descriptor_ui": "D007989", "major_topic": true }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Motivation", "descriptor_ui": "D009042", "major_topic": true }, { "descriptor": "Personal Satisfaction", "descriptor_ui": "D010549", "major_topic": true }, { "descriptor": "Sexual Behavior", "descriptor_ui": "D012725", "major_topic": true }, { "descriptor": "Young Adult", "descriptor_ui": "D055815", "major_topic": false } ], "publication": { "conference_name": null, "date": "2025 Feb 12", "date_precision": "day", "issue": "", "normalized_date": "2025-02-12", "pages": "", "proceedings_title": null, "publisher": "", "title": "Journal of behavioral addictions", "volume": "", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Motives for pornography use and women's sexual wellbeing: Insights from a 42-country study.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "While the intestinal epithelium has the highest cellular turnover rates in the mammalian body, it is also considered one of the tissues most resilient to aging-related disorders. Here, we reveal an innate protective mechanism that safeguards intestinal stem cells (ISCs) from environmental conditions in the aged intestine. Using in vivo phenotypic analysis, transcriptomics, and in vitro intestinal organoid studies, we show that age-dependent activation of interferon-gamma (IFN-gamma) signaling and inactivation of extracellular signal-regulated kinase/mitogen-activated protein kinase (ERK/MAPK) signaling are responsible for establishing an equilibrium of Lgr5(+) ISCs-between active and quiescent states-to preserve the ISC pool during aging. Furthermore, we show that differentiated cells have different sensitivities to each of the two signaling pathways, which may induce aging-related, functional, and metabolic changes in the body. Thus, our findings reveal an exquisitely balanced, age-dependent signaling mechanism that preserves stem cells at the expense of differentiated cells.", "classifications": [ { "id": "JPMJCR2023", "label": "JPMJCR2023", "researcher": "Fumiko Toyoshima", "type": "grant" }, { "id": "Toyoshima", "label": "Group Toyoshima", "parent": "Toyoshima", "type": "group" }, { "id": "Yamamoto", "label": "Group Yamamoto", "parent": "Toyoshima", "type": "group" }, { "id": "Toyoshima", "label": "Team Toyoshima", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "May", "last_name": "Nakajima-Koyama", "name": null }, { "creator_type": "author", "first_name": "Mio", "last_name": "Kabata", "name": null }, { "creator_type": "author", "first_name": "Joonseong", "last_name": "Lee", "name": null }, { "creator_type": "author", "first_name": "Yuko", "last_name": "Sogabe", "name": null }, { "creator_type": "author", "first_name": "Satoko", "last_name": "Sakurai", "name": null }, { "creator_type": "author", "first_name": "Akira", "last_name": "Hirota", "name": null }, { "creator_type": "author", "first_name": "Mizuki", "last_name": "Kimura", "name": null }, { "creator_type": "author", "first_name": "Tomonori", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Imoto", "name": null }, { "creator_type": "author", "first_name": "Kohei", "last_name": "Kometani", "name": null }, { "creator_type": "author", "first_name": "Yoko", "last_name": "Hamazaki", "name": null }, { "creator_type": "author", "first_name": "Yasuaki", "last_name": "Hiraoka", "name": null }, { "creator_type": "author", "first_name": "Mitinori", "last_name": "Saitou", "name": null }, { "creator_type": "author", "first_name": "Eisuke", "last_name": "Nishida", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Yamamoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.celrep.2025.115286" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "39952238" } }, "mesh": [ { "descriptor": "Aging", "descriptor_ui": "D000375", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Interferon-gamma", "descriptor_ui": "D007371", "major_topic": true }, { "descriptor": "Intestinal Mucosa", "descriptor_ui": "D007413", "major_topic": true }, { "descriptor": "Intestines", "descriptor_ui": "D007422", "major_topic": true }, { "descriptor": "MAP Kinase Signaling System", "descriptor_ui": "D020935", "major_topic": true }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Receptors, G-Protein-Coupled", "descriptor_ui": "D043562", "major_topic": false }, { "descriptor": "Stem Cells", "descriptor_ui": "D013234", "major_topic": true } ], "publication": { "conference_name": null, "date": "2025 Feb 11", "date_precision": "day", "issue": "", "normalized_date": "2025-02-11", "pages": "115286", "proceedings_title": null, "publisher": "", "title": "Cell reports", "volume": "", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "The balance between IFN-gamma and ERK/MAPK signaling activities ensures lifelong maintenance of intestinal stem cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The physiological functions of supersulfides, inorganic and organic sulfides with sulfur catenation, have been extensively studied. Their synthesis is mainly mediated by mitochondrial cysteinyl-tRNA synthetase (CARS2) that functions as a principal cysteine persulfide synthase. This study aimed to investigate the role of supersulfides in joint homeostasis and bone regeneration. Using Cars2(AINK/+) mutant mice, in which the KIIK motif of CARS2 essential for supersulfide production was replaced with AINK, we evaluated the role of supersulfides in fracture healing and cartilage homeostasis during osteoarthritis (OA). Tibial fracture surgery was performed on the wild-type (Cars2(+/+)) and Cars2(AINK/+) mice littermates. Bulk RNA-seq analysis for the osteochondral regeneration in the fracture model showed increased inflammatory markers and reduced osteogenic factors, indicative of impaired bone regeneration, in Cars2(AINK/+) mice. Destabilization of the medial meniscus (DMM) surgery was performed to produce the mouse OA model. Histological analyses with Osteoarthritis Research Society International and synovitis scores revealed accelerated OA progression in Cars2(AINK/+) mice compared with that in Cars2(+/+) mice. To assess the effects of supersulfides on OA progression, glutathione trisulfide (GSSSG) or saline was periodically injected into the mouse knee joints after the DMM surgery. Thus, supersulfides derived from CARS2 and GSSSG exogenously administered significantly inhibited inflammation and lipid peroxidation of the joint cartilage, possibly through suppression of ferroptosis, during OA development. This study represents a significant advancement in understanding anti-inflammatory and anti-oxidant functions of supersulfides in skeletal tissues and may have a clinical relevance for the bone healing and OA therapeutics.", "classifications": [ { "id": "JPMJCR2024", "label": "JPMJCR2024", "researcher": "Motohiro Nishida", "type": "grant" }, { "id": "Akaike", "label": "Group Akaike", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Group Nishida", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Miki", "last_name": "Maemura", "name": null }, { "creator_type": "author", "first_name": "Masanobu", "last_name": "Morita", "name": null }, { "creator_type": "author", "first_name": "Seiryo", "last_name": "Ogata", "name": null }, { "creator_type": "author", "first_name": "Yoichi", "last_name": "Miyamoto", "name": null }, { "creator_type": "author", "first_name": "Tomoaki", "last_name": "Ida", "name": null }, { "creator_type": "author", "first_name": "Kazuhiro", "last_name": "Shibusaka", "name": null }, { "creator_type": "author", "first_name": "Soichiro", "last_name": "Negishi", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Hosonuma", "name": null }, { "creator_type": "author", "first_name": "Taku", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Jun", "last_name": "Yoshitake", "name": null }, { "creator_type": "author", "first_name": "Tsuyoshi", "last_name": "Takata", "name": null }, { "creator_type": "author", "first_name": "Tetsuro", "last_name": "Matsunaga", "name": null }, { "creator_type": "author", "first_name": "Eikan", "last_name": "Mishima", "name": null }, { "creator_type": "author", "first_name": "Uladzimir", "last_name": "Barayeu", "name": null }, { "creator_type": "author", "first_name": "Takaaki", "last_name": "Akaike", "name": null }, { "creator_type": "author", "first_name": "Fumiko", "last_name": "Yano", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.redox.2025.103545" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "39983344" } }, "mesh": [ { "descriptor": "Amino Acyl-tRNA Synthetases", "descriptor_ui": "D000604", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Bone Regeneration", "descriptor_ui": "D001861", "major_topic": true }, { "descriptor": "Cartilage", "descriptor_ui": "D002356", "major_topic": false }, { "descriptor": "Fractures, Bone", "descriptor_ui": "D050723", "major_topic": false }, { "descriptor": "Glutathione", "descriptor_ui": "D005978", "major_topic": true }, { "descriptor": "Homeostasis", "descriptor_ui": "D006706", "major_topic": false }, { "descriptor": "Joints", "descriptor_ui": "D007596", "major_topic": true }, { "descriptor": "Knee Joint", "descriptor_ui": "D007719", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Mutant Strains", "descriptor_ui": "D008817", "major_topic": false }, { "descriptor": "Osteoarthritis", "descriptor_ui": "D010003", "major_topic": false }, { "descriptor": "Sulfides", "descriptor_ui": "D013440", "major_topic": true } ], "publication": { "conference_name": null, "date": "2025 Feb 11", "date_precision": "day", "issue": "", "normalized_date": "2025-02-11", "pages": "103545", "proceedings_title": null, "publisher": "", "title": "Redox biology", "volume": "81", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Supersulfides contribute to joint homeostasis and bone regeneration.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Upper gastrointestinal cancer (UGC) sometimes metastasizes to the splenic hilum lymph node (SHLN). However, surgical removal of SHLN is technically difficult, and the risk of postoperative complications is high. Although there are models that predict SHLN metastasis, they usually only provide point estimates of risk, and there is a lack of sufficient information. To address this issue, we aimed to develop a Bayesian logistic regression model called Bayes-SHLNM. The performance of the models was compared with that of the frequentist logistic regression (FLR) model as a benchmark, and the posterior probability distribution (PPD) was shown individually. The performance of Bayes-SHLNM was equivalent to that of the FLR model, and the PPD for each case was visualized as the uncertainty. These results indicate that the Bayes-SHLNM model has the potential to be used as a decision support system in clinical settings where uncertainty is high.", "classifications": [ { "id": "Hamamoto", "label": "Group Hamamoto", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Kenichi", "last_name": "Ishizu", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Nobuji", "last_name": "Kouno", "name": null }, { "creator_type": "author", "first_name": "Ken", "last_name": "Takasawa", "name": null }, { "creator_type": "author", "first_name": "Katsuji", "last_name": "Takeda", "name": null }, { "creator_type": "author", "first_name": "Kota", "last_name": "Matsui", "name": null }, { "creator_type": "author", "first_name": "Masashi", "last_name": "Nishino", "name": null }, { "creator_type": "author", "first_name": "Tsutomu", "last_name": "Hayashi", "name": null }, { "creator_type": "author", "first_name": "Yukinori", "last_name": "Yamagata", "name": null }, { "creator_type": "author", "first_name": "Shigeyuki", "last_name": "Matsui", "name": null }, { "creator_type": "author", "first_name": "Takaki", "last_name": "Yoshikawa", "name": null }, { "creator_type": "author", "first_name": "Ryuji", "last_name": "Hamamoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41746-025-01480-x" }, "pmcid": { "normalized": "PMC11814149" }, "pmid": { "normalized": "39934302" } }, "mesh": [], "publication": { "conference_name": null, "date": "2025 Feb 11", "date_precision": "day", "issue": "1", "normalized_date": "2025-02-11", "pages": "93", "proceedings_title": null, "publisher": "", "title": "NPJ digital medicine", "volume": "8", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Establishment of a machine learning model for predicting splenic hilar lymph node metastasis.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Despite the importance of genetic testing for risk assessment and treatment in breast cancer, the prognostic impact of germline pathogenic variants (PVs), especially in Asian populations, is unclear. We assessed the impact of germline PVs in patients with early-stage breast cancer. This study included 7278 Japanese multihospital registry patients. PVs of ATM, BRCA1, BRCA2, CDH1, CHEK2, NBN, NF1, PALB2, PTEN, STK11, and TP53 were evaluated. PV and non-PV carriers were matched by age, histology, and stage. Associations between PVs and survival were assessed. The primary outcome was invasive disease-free survival (IDFS). Secondary outcomes included relapse-free survival (RFS), overall survival, and breast cancer-specific survival. We identified 320 (4.4%) patients with BRCA1/2 PVs and 79 (1.1%) with PVs other than BRCA1/2 (non-BRCA1/2). A total of 360 patients (BRCA1/2, n = 289; non-BRCA1/2, n = 71) were matched to 720 noncarriers. Patients with BRCA1/2 PVs had significantly shorter 10-year IDFS (adjusted hazard ratio (aHR) = 2.15; 95% confidence interval (CI), 1.61-2.86; p < 0.001); and RFS (aHR = 1.74; 95% CI, 1.25-2.44; p = 0.001) than noncarriers. Among patients with hormone receptor-positive HER2-negative breast cancer, BRCA1/2 PV carriers exhibited significantly shorter 10-year IDFS than noncarriers, even those with stage I/II disease (total, aHR = 2.23; 95% CI, 1.55-3.23; p < 0.001, Stage I/II, aHR = 2.22; 95% CI, 1.43-3.44; p < 0.001). There was no significant difference in 10-year IDFS between the non-BRCA1/2 PV carrier and noncarrier groups (aHR = 1.40; 95% CI, 0.67-2.93; p = 0.37). Asian patients with breast cancer carrying germline BRCA1/2 PV, even those with a low recurrence risk, have significantly shorter 10-year IDFS than noncarriers.", "classifications": [ { "id": "Hamamoto", "label": "Group Hamamoto", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Rui", "last_name": "Kitadai", "name": null }, { "creator_type": "author", "first_name": "Shu", "last_name": "Yazaki", "name": null }, { "creator_type": "author", "first_name": "Aya", "last_name": "Kuchiba", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Yamanaka", "name": null }, { "creator_type": "author", "first_name": "Sho", "last_name": "Shiino", "name": null }, { "creator_type": "author", "first_name": "Chisako", "last_name": "Yamauchi", "name": null }, { "creator_type": "author", "first_name": "Kenichi", "last_name": "Harano", "name": null }, { "creator_type": "author", "first_name": "Motonobu", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Yosuke", "last_name": "Hirotsu", "name": null }, { "creator_type": "author", "first_name": "Hisaki", "last_name": "Aiba", "name": null }, { "creator_type": "author", "first_name": "Teruhiko", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Ryuji", "last_name": "Hamamoto", "name": null }, { "creator_type": "author", "first_name": "Chikako", "last_name": "Shimizu", "name": null }, { "creator_type": "author", "first_name": "Akihiko", "last_name": "Shimomura", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Kojima", "name": null }, { "creator_type": "author", "first_name": "Tatsunori", "last_name": "Shimoi", "name": null }, { "creator_type": "author", "first_name": "Yukihide", "last_name": "Momozawa", "name": null }, { "creator_type": "author", "first_name": "Kazuki", "last_name": "Sudo", "name": null }, { "creator_type": "author", "first_name": "Masayuki", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Kuniko", "last_name": "Sunami", "name": null }, { "creator_type": "author", "first_name": "Megumi", "last_name": "Hori", "name": null }, { "creator_type": "author", "first_name": "Kota", "last_name": "Katanoda", "name": null }, { "creator_type": "author", "first_name": "Yoko", "last_name": "Shimada", "name": null }, { "creator_type": "author", "first_name": "Yuji", "last_name": "Yamashita", "name": null }, { "creator_type": "author", "first_name": "Takahiro", "last_name": "Kogawa", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Murata", "name": null }, { "creator_type": "author", "first_name": "Saori", "last_name": "Fujiwara", "name": null }, { "creator_type": "author", "first_name": "Yohei", "last_name": "Miyagi", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Nakagomi", "name": null }, { "creator_type": "author", "first_name": "Kazunoshin", "last_name": "Tachibana", "name": null }, { "creator_type": "author", "first_name": "Masao", "last_name": "Omata", "name": null }, { "creator_type": "author", "first_name": "Tohru", "last_name": "Ohtake", "name": null }, { "creator_type": "author", "first_name": "Akihiko", "last_name": "Suto", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Onishi", "name": null }, { "creator_type": "author", "first_name": "Yoichi", "last_name": "Naito", "name": null }, { "creator_type": "author", "first_name": "Toshinari", "last_name": "Yamashita", "name": null }, { "creator_type": "author", "first_name": "Kan", "last_name": "Yonemori", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Kohno", "name": null }, { "creator_type": "author", "first_name": "Kouya", "last_name": "Shiraishi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/cas.70002" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "39930910" } }, "mesh": [ { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "BRCA1 Protein", "descriptor_ui": "D019313", "major_topic": false }, { "descriptor": "BRCA2 Protein", "descriptor_ui": "D024682", "major_topic": false }, { "descriptor": "Breast Neoplasms", "descriptor_ui": "D001943", "major_topic": true }, { "descriptor": "Disease-Free Survival", "descriptor_ui": "D018572", "major_topic": false }, { "descriptor": "East Asian People", "descriptor_ui": "D000095225", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Genetic Predisposition to Disease", "descriptor_ui": "D020022", "major_topic": false }, { "descriptor": "Genetic Testing", "descriptor_ui": "D005820", "major_topic": false }, { "descriptor": "Germ-Line Mutation", "descriptor_ui": "D018095", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Prognosis", "descriptor_ui": "D011379", "major_topic": false } ], "publication": { "conference_name": null, "date": "2025 Feb 10", "date_precision": "day", "issue": "", "normalized_date": "2025-02-10", "pages": "", "proceedings_title": null, "publisher": "", "title": "Cancer science", "volume": "", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Germline Pathogenic Variants and Clinical Outcomes in Asian Patients With Breast Cancer.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Hereditary protein C (PC) deficiency is an inherited thrombophilic disorder caused by variants in the PC gene (PROC). We identified a novel PROC variant, c.302G>T, p.Cys101Phe (C101F), in a patient with type I PC deficiency. We analyzed the intracellular dynamics of the C101F variant of PC (PC-C101F) to elucidate the pathogenic mechanism underlying this condition. Wild-type PC (PC-WT) and PC-C101F were transiently expressed in HEK293 cells for expression and functional analyses. The PC antigen levels in the cell lysate and culture supernatant of PC-C101F-expressing cells were significantly lower than those of PC-WT-expressing cells. In cycloheximide (CHX) chase experiments, the intracellular PC antigen level gradually decreased in PC-C101F-expressing cells, but remained stable at 0 and 6 h in the presence of CHX/MG132. No significant difference in co-localization with the endoplasmic reticulum was observed between PC-C101F and PC-WT. 101Cys forms a disulfide bond with 106Cys, which is crucial for maintaining the conformation of PC. PC-C101F likely results in protein misfolding and proteasomal degradation, leading to type I PC deficiency. These findings highlight the importance of cysteine residues in the three-dimensional structure of PC and provide insight into the mechanism of type I PC deficiency.", "classifications": [ { "id": "Nishikii", "label": "Group Nishikii", "parent": "Shintaku", "type": "group" }, { "id": "Shintaku", "label": "Team Shintaku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Rikuto", "last_name": "Yui", "name": null }, { "creator_type": "author", "first_name": "Satomi", "last_name": "Nagaya", "name": null }, { "creator_type": "author", "first_name": "Ibuki", "last_name": "Yasuda", "name": null }, { "creator_type": "author", "first_name": "Tomoki", "last_name": "Togashi", "name": null }, { "creator_type": "author", "first_name": "Yuika", "last_name": "Kikuchi", "name": null }, { "creator_type": "author", "first_name": "Kengo", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Makiko", "last_name": "Meguro-Horike", "name": null }, { "creator_type": "author", "first_name": "Shin-Ichi", "last_name": "Horike", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Kawasaki", "name": null }, { "creator_type": "author", "first_name": "Hidekazu", "last_name": "Nishikii", "name": null }, { "creator_type": "author", "first_name": "Eriko", "last_name": "Morishita", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/s12185-025-03943-z" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "39928218" } }, "mesh": [ { "descriptor": "Endoplasmic Reticulum", "descriptor_ui": "D004721", "major_topic": false }, { "descriptor": "HEK293 Cells", "descriptor_ui": "D057809", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": true }, { "descriptor": "Protein C", "descriptor_ui": "D011486", "major_topic": true }, { "descriptor": "Protein C Deficiency", "descriptor_ui": "D020151", "major_topic": true }, { "descriptor": "Proteolysis", "descriptor_ui": "D059748", "major_topic": true } ], "publication": { "conference_name": null, "date": "2025 Feb 10", "date_precision": "day", "issue": "", "normalized_date": "2025-02-10", "pages": "", "proceedings_title": null, "publisher": "", "title": "International journal of hematology", "volume": "", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "The novel protein C variant p.C101F results in early intracellular degradation that drives type I protein C deficiency.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "C(4) plants have C(4) photosynthetic cycle, a CO(2)-concentrating pump that functions across mesophyll (M) and bundle sheath (BS) cells. M chloroplasts aggregate toward BS cells in response to environmental stress, which would contribute to adjustment in C(4) photosynthetic cycle. However, it remains unclear whether M chloroplast movement is an intercellular response mediated by BS cells. One major challenge to resolve this is the difficulty in observing chloroplast movement due to scattering and absorption of observation light in live-leaf tissues. We established a live leaf-section imaging technique that enables the long-term observation of sections of chemically unfixed leaf blades, with which we quantitatively analyzed M chloroplast movements. Another challenge in clarifying the contribution of BS cells to M chloroplast movement is the selective ablation of BS cells without impairing M cell function. To investigate the necessity of BS cells for M chloroplast movement, we developed a method to remove BS cells only based on differences in shape between M and BS cells. We also found that chloroplasts in M cells without adjacent BS cell contents did not show typical aggregative movement. This indicates that the M chloroplast aggregative movement occurs during communication with BS cells.", "classifications": [ { "id": "Sato", "label": "Group Sato", "parent": "Tsuchiya", "type": "group" }, { "id": "Tsuchiya", "label": "Team Tsuchiya", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yuta", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Takao", "last_name": "Oi", "name": null }, { "creator_type": "author", "first_name": "Yoshikatsu", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Mitsutaka", "last_name": "Taniguchi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41598-025-86153-1" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "39900954" } }, "mesh": [ { "descriptor": "Chloroplasts", "descriptor_ui": "D002736", "major_topic": true }, { "descriptor": "Mesophyll Cells", "descriptor_ui": "D058503", "major_topic": true }, { "descriptor": "Photosynthesis", "descriptor_ui": "D010788", "major_topic": false }, { "descriptor": "Plant Leaves", "descriptor_ui": "D018515", "major_topic": true } ], "publication": { "conference_name": null, "date": "2025 Feb 3", "date_precision": "day", "issue": "1", "normalized_date": "2025-02-03", "pages": "3447", "proceedings_title": null, "publisher": "", "title": "Scientific reports", "volume": "15", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Bundle sheath cell-dependent chloroplast movement in mesophyll cells of C(4) plants analyzed using live leaf-section imaging.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "G protein-coupled receptors (GPCRs) exist in the conformational equilibrium between inactive state and active state, where the proportion of active state in the absence of a ligand determines the basal activity of GPCRs. Although many GPCRs have different basal activity, it is still unclear whether physiological stresses such as substrate stiffness affect the basal activity of GPCRs. In this study, we identified that purinergic P2Y(6) receptor (P2Y(6)R) induced spontaneous Ca(2+) oscillation without a nucleotide ligand when cells were cultured in a silicon chamber. This P2Y(6)R-dependent Ca(2+) oscillation was absent in cells cultured in glass dishes. Coating substrates, including collagen, laminin, and fibronectin, did not affect the P2Y(6)R spontaneous activity. Mutation of the extracellular Arg-Gly-Asp (RGD) motif of P2Y(6)R inhibited spontaneous activity. Additionally, extracellular Ca(2+) was required for P2Y(6)R-dependent spontaneous Ca(2+) oscillation. The GPCR screening assay identified cells expressing 10 GPCRs, including purinergic P2Y(1)R, P2Y(2)R, and P2Y(6)R, that exhibited spontaneous Ca(2+) oscillation under cell culture soft substrate. Our results suggest that stiffness of the cell adhesion surface modulates spontaneous activities of several GPCRs, including P2Y(6)R, through a ligand-independent mechanism.", "classifications": [ { "id": "JPMJCR2024", "label": "JPMJCR2024", "researcher": "Motohiro Nishida", "type": "grant" }, { "id": "Nishida", "label": "Group Nishida", "parent": "Nishida", "type": "group" }, { "id": "Nishimura", "label": "Group Nishimura", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Akiyuki", "last_name": "Nishimura", "name": null }, { "creator_type": "author", "first_name": "Kazuhiro", "last_name": "Nishiyama", "name": null }, { "creator_type": "author", "first_name": "Tomoya", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Xinya", "last_name": "Mi", "name": null }, { "creator_type": "author", "first_name": "Yuri", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Asuka", "last_name": "Inoue", "name": null }, { "creator_type": "author", "first_name": "Junken", "last_name": "Aoki", "name": null }, { "creator_type": "author", "first_name": "Motohiro", "last_name": "Nishida", "name": null } ], "identifiers": { "doi": { "normalized": "10.3390/cells14030216" }, "pmcid": { "normalized": "PMC11817550" }, "pmid": { "normalized": "39937007" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Calcium", "descriptor_ui": "D002118", "major_topic": false }, { "descriptor": "Calcium Signaling", "descriptor_ui": "D020013", "major_topic": false }, { "descriptor": "Cell Culture Techniques", "descriptor_ui": "D018929", "major_topic": true }, { "descriptor": "HEK293 Cells", "descriptor_ui": "D057809", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Ligands", "descriptor_ui": "D008024", "major_topic": false }, { "descriptor": "Receptors, Purinergic P2", "descriptor_ui": "D018048", "major_topic": true } ], "publication": { "conference_name": null, "date": "2025 Feb 3", "date_precision": "day", "issue": "3", "normalized_date": "2025-02-03", "pages": "", "proceedings_title": null, "publisher": "", "title": "Cells", "volume": "14", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Ligand-Independent Spontaneous Activation of Purinergic P2Y(6) Receptor Under Cell Culture Soft Substrate.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "We established a volumetric trans-scale imaging system with an ultra-large field-of-view (FOV) that enables simultaneous observation of millions of cellular dynamics in centimeter-wide three-dimensional (3D) tissues and embryos. Using a custom-made giant lens system with a magnification of x2 and a numerical aperture (NA) of 0.25, and a CMOS camera with more than 100 megapixels, we built a trans-scale scope AMATERAS-2, and realized fluorescence imaging with a transverse spatial resolution of approximately 1.1 microm across an FOV of approximately 1.5x1.0 cm(2). The 3D resolving capability was realized through a combination of optical and computational sectioning techniques tailored for our low-power imaging system. We applied the imaging technique to 1.2 cm-wide section of mouse brain, and successfully observed various regions of the brain with sub-cellular resolution in a single FOV. We also performed time-lapse imaging of a 1-cm-wide vascular network during quail embryo development for over 24 hr, visualizing the movement of over 4.0x10(5) vascular endothelial cells and quantitatively analyzing their dynamics. Our results demonstrate the potential of this technique in accelerating production of comprehensive reference maps of all cells in organisms and tissues, which contributes to understanding developmental processes, brain functions, and pathogenesis of disease, as well as high-throughput quality check of tissues used for transplantation medicine.", "classifications": [ { "id": "JPMJCR1926", "label": "JPMJCR1926", "researcher": "Hironobu Fujiwara", "type": "grant" }, { "id": "Fujiwara", "label": "Group Fujiwara", "parent": "Fujiwara", "type": "group" }, { "id": "Onami", "label": "Group Onami", "parent": "Fujiwara", "type": "group" }, { "id": "Fujiwara", "label": "Team Fujiwara", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Taro", "last_name": "Ichimura", "name": null }, { "creator_type": "author", "first_name": "Taishi", "last_name": "Kakizuka", "name": null }, { "creator_type": "author", "first_name": "Yoshitsugu", "last_name": "Taniguchi", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Ejima", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Keiko", "last_name": "Itano", "name": null }, { "creator_type": "author", "first_name": "Kaoru", "last_name": "Seiriki", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Ko", "last_name": "Sugawara", "name": null }, { "creator_type": "author", "first_name": "Hiroya", "last_name": "Itoga", "name": null }, { "creator_type": "author", "first_name": "Shuichi", "last_name": "Onami", "name": null }, { "creator_type": "author", "first_name": "Takeharu", "last_name": "Nagai", "name": null } ], "identifiers": { "doi": { "normalized": "10.7554/elife.93633" }, "pmcid": { "normalized": "PMC11790249" }, "pmid": { "normalized": "39899352" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Brain", "descriptor_ui": "D001921", "major_topic": true }, { "descriptor": "Embryo, Mammalian", "descriptor_ui": "D004622", "major_topic": true }, { "descriptor": "Embryo, Nonmammalian", "descriptor_ui": "D004625", "major_topic": false }, { "descriptor": "Imaging, Three-Dimensional", "descriptor_ui": "D021621", "major_topic": true }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Optical Imaging", "descriptor_ui": "D061848", "major_topic": true }, { "descriptor": "Quail", "descriptor_ui": "D011784", "major_topic": false }, { "descriptor": "Time-Lapse Imaging", "descriptor_ui": "D059008", "major_topic": false } ], "publication": { "conference_name": null, "date": "2025 Feb 3", "date_precision": "day", "issue": "", "normalized_date": "2025-02-03", "pages": "", "proceedings_title": null, "publisher": "", "title": "eLife", "volume": "13", "year": 2025 }, "ssbd": { "database": [ "ssbd-database-000409" ], "repository": [ "ssbd-repos-000409" ] }, "title": "Volumetric trans-scale imaging of massive quantity of heterogeneous cell populations in centimeter-wide tissue and embryo.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Precisely controlled remodeling of the basement membrane (BM) is crucial for morphogenesis, but its molecular and tissue-level dynamics, underlying mechanisms, and functional significance in mammals remain largely unknown due to limited visualization tools. We developed mouse lines in which the endogenous collagen IV gene (Col4a2) was fused with a fluorescent tag. Through live imaging of developing hair follicles, we reveal a spatial gradient in the turnover rate of COL4A2 that is closely coupled with both the BM expansion rate and the proliferation rate of epithelial progenitors. Epithelial progenitors are displaced with directionally expanding BMs but do not actively migrate on stationary BM. The addition of a matrix metalloproteinase inhibitor delays COL4A2 turnover, restrains BM expansion, and increases perpendicular divisions of epithelial progenitors, altering hair follicle morphology. Our findings highlight the spatially distinct dynamics of BM and their key roles in orchestrating progenitor cell behavior and organ shape during development.", "classifications": [ { "id": "JPMJCR1926", "label": "JPMJCR1926", "researcher": "Hironobu Fujiwara", "type": "grant" }, { "id": "Fujiwara", "label": "Group Fujiwara", "parent": "Fujiwara", "type": "group" }, { "id": "Fujiwara", "label": "Team Fujiwara", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Duligengaowa", "last_name": "Wuergezhen", "name": null }, { "creator_type": "author", "first_name": "Eleonore", "last_name": "Gindroz", "name": null }, { "creator_type": "author", "first_name": "Ritsuko", "last_name": "Morita", "name": null }, { "creator_type": "author", "first_name": "Kei", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Takaya", "last_name": "Abe", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Kiyonari", "name": null }, { "creator_type": "author", "first_name": "Hironobu", "last_name": "Fujiwara", "name": null } ], "identifiers": { "doi": { "normalized": "10.1083/jcb.202404003" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "39656438" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Basement Membrane", "descriptor_ui": "D001485", "major_topic": true }, { "descriptor": "Cell Movement", "descriptor_ui": "D002465", "major_topic": false }, { "descriptor": "Cell Proliferation", "descriptor_ui": "D049109", "major_topic": false }, { "descriptor": "Collagen Type IV", "descriptor_ui": "D024141", "major_topic": true }, { "descriptor": "Epithelial Cells", "descriptor_ui": "D004847", "major_topic": false }, { "descriptor": "Green Fluorescent Proteins", "descriptor_ui": "D049452", "major_topic": true }, { "descriptor": "Hair Follicle", "descriptor_ui": "D018859", "major_topic": true }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Transgenic", "descriptor_ui": "D008822", "major_topic": false }, { "descriptor": "Morphogenesis", "descriptor_ui": "D009024", "major_topic": true }, { "descriptor": "Stem Cells", "descriptor_ui": "D013234", "major_topic": false } ], "publication": { "conference_name": null, "date": "2025 Feb 3", "date_precision": "day", "issue": "2", "normalized_date": "2025-02-03", "pages": "e202404003", "proceedings_title": null, "publisher": "", "title": "The Journal of cell biology", "volume": "224", "year": 2025 }, "ssbd": { "database": [], "repository": [ "ssbd-repos-000298" ] }, "title": "An eGFP-Col4a2 mouse model reveals basement membrane dynamics underlying hair follicle morphogenesis.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Early detection of esophageal cancer is essential for esophagogastroduodenoscopy and histopathological diagnosis. However, endoscopic examinations are sometimes invasive, which limits their clinical application and compliance, and traditional blood tumor markers are unsuitable for cancer screening. The current study aimed to evaluate the usefulness of sulfur metabolites as new biomarkers for esophageal cancer using blood samples and exhaled breath condensate (EBC), which can be readily obtained and is non-invasive. We collected EBC and plasma samples from 50 patients with esophageal cancer and 30 healthy controls. Sulfur metabolome analysis using tandem mass spectrometry was performed to compare the metabolic profile between the two groups. Supersulfide metabolic profiles were different between the two cohorts. Supersulfide metabolome analysis showed that cysteine hydropersulfide (CysSSH) and homocysteine hydropersulfide (HomoCysSSH) were increased in the plasma of patients with esophageal cancer. Elevated levels of HomoCysSSH could distinguish patients with esophageal cancer from healthy subjects (area under the curve [AUC]: 0.93, sensitivity: 89%, specificity: 96%). Interestingly, we also detected an elevation of supersulfides in the EBC analysis. CysSSH levels significantly increased in the EBC recovered from patients with esophageal cancer (AUC: 0.71, sensitivity: 60%, specificity: 96%). In addition, the observed level was correlated with that of HomoCysSSH in the plasma (r = 0.27). Supersulfides, such as CysSSH and HomoCysSSH, are potential biomarkers for detecting esophageal cancer. CysSSH from EBC may serve as a valuable non-invasive biomarker with similar detection ability but with superior precision and convenience compared with the currently available blood biomarkers.", "classifications": [ { "id": "JPMJCR2024", "label": "JPMJCR2024", "researcher": "Motohiro Nishida", "type": "grant" }, { "id": "Akaike", "label": "Group Akaike", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Group Nishida", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Seji", "last_name": "Asamitsu", "name": null }, { "creator_type": "author", "first_name": "Yohei", "last_name": "Ozawa", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Okamoto", "name": null }, { "creator_type": "author", "first_name": "Seiryo", "last_name": "Ogata", "name": null }, { "creator_type": "author", "first_name": "Tetsuro", "last_name": "Matsunaga", "name": null }, { "creator_type": "author", "first_name": "Jun", "last_name": "Yoshitake", "name": null }, { "creator_type": "author", "first_name": "Kazuki", "last_name": "Fusegawa", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Taniyama", "name": null }, { "creator_type": "author", "first_name": "Chiaki", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Hirotaka", "last_name": "Ishida", "name": null }, { "creator_type": "author", "first_name": "Takaaki", "last_name": "Abe", "name": null }, { "creator_type": "author", "first_name": "Hozumi", "last_name": "Motohashi", "name": null }, { "creator_type": "author", "first_name": "Takaaki", "last_name": "Akaike", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Kamei", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/cas.16430" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "39895210" } }, "mesh": [ { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Biomarkers, Tumor", "descriptor_ui": "D014408", "major_topic": true }, { "descriptor": "Breath Tests", "descriptor_ui": "D001944", "major_topic": false }, { "descriptor": "Case-Control Studies", "descriptor_ui": "D016022", "major_topic": false }, { "descriptor": "Cysteine", "descriptor_ui": "D003545", "major_topic": false }, { "descriptor": "Early Detection of Cancer", "descriptor_ui": "D055088", "major_topic": false }, { "descriptor": "Esophageal Neoplasms", "descriptor_ui": "D004938", "major_topic": true }, { "descriptor": "Exhalation", "descriptor_ui": "D045853", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Homocysteine", "descriptor_ui": "D006710", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Metabolome", "descriptor_ui": "D055442", "major_topic": true }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Sensitivity and Specificity", "descriptor_ui": "D012680", "major_topic": false }, { "descriptor": "Sulfides", "descriptor_ui": "D013440", "major_topic": true } ], "publication": { "conference_name": null, "date": "2025 Feb 2", "date_precision": "day", "issue": "", "normalized_date": "2025-02-02", "pages": "", "proceedings_title": null, "publisher": "", "title": "Cancer science", "volume": "", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Supersulfide metabolome of exhaled breath condensate applied as diagnostic biomarkers for esophageal cancer.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The applicability of a deep learning model for the virtual staining of plant cell structures using bright-field microscopy was investigated. The training dataset consisted of microscopy images of tobacco BY-2 cells with the plasma membrane stained with the fluorescent dye PlasMem Bright Green and the cell nucleus labeled with Histone-red fluorescent protein. The trained models successfully detected the expansion of cell nuclei upon aphidicolin treatment and a decrease in the cell aspect ratio upon propyzamide treatment, demonstrating its utility in cell morphometry. The model also accurately documented the shape of Arabidopsis pavement cells in both wild type and the bpp125 triple mutant, which has an altered pavement cell phenotype. Metrics such as cell area, circularity, and solidity obtained from virtual staining analyses were highly correlated with those obtained by manual measurements of cell features from microscopy images. Furthermore, the versatility of virtual staining was highlighted by its application to track chloroplast movement in Egeria densa. The method was also effective for classifying live and dead BY-2 cells using texture-based machine learning, suggesting that virtual staining can be applied beyond typical segmentation tasks. Although this method still has some limitations, its non-invasive nature and efficiency make it highly suitable for label-free, dynamic, and high-throughput analyses in quantitative plant cell biology.", "classifications": [ { "id": "JPMJCR2121", "label": "JPMJCR2121", "researcher": "Minako Ueda", "type": "grant" }, { "id": "Higaki", "label": "Group Higaki", "parent": "Ueda", "type": "group" }, { "id": "Ueda", "label": "Group Ueda", "parent": "Ueda", "type": "group" }, { "id": "Ueda", "label": "Team Ueda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Manami", "last_name": "Ichita", "name": null }, { "creator_type": "author", "first_name": "Haruna", "last_name": "Yamamichi", "name": null }, { "creator_type": "author", "first_name": "Takumi", "last_name": "Higaki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/s11103-025-01558-w" }, "pmcid": { "normalized": "PMC11782351" }, "pmid": { "normalized": "39885095" } }, "mesh": [ { "descriptor": "Arabidopsis", "descriptor_ui": "D017360", "major_topic": false }, { "descriptor": "Cell Nucleus", "descriptor_ui": "D002467", "major_topic": false }, { "descriptor": "Chloroplasts", "descriptor_ui": "D002736", "major_topic": false }, { "descriptor": "Deep Learning", "descriptor_ui": "D000077321", "major_topic": false }, { "descriptor": "Microscopy", "descriptor_ui": "D008853", "major_topic": true }, { "descriptor": "Nicotiana", "descriptor_ui": "D014026", "major_topic": false }, { "descriptor": "Plant Cells", "descriptor_ui": "D059828", "major_topic": true }, { "descriptor": "Staining and Labeling", "descriptor_ui": "D013194", "major_topic": true } ], "publication": { "conference_name": null, "date": "2025 Jan 31", "date_precision": "day", "issue": "1", "normalized_date": "2025-01-31", "pages": "29", "proceedings_title": null, "publisher": "", "title": "Plant molecular biology", "volume": "115", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Virtual staining from bright-field microscopy for label-free quantitative analysis of plant cell structures.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Orchids have evolved flowers with unique morphologies through coevolution with pollinators, such as insects. Among the floral organs, the lip (labellum), one of the three petals, exhibits a distinctive shape and plays a crucial role in attracting pollinators and facilitating pollination in many orchids. The lip of the terrestrial orchid Habenaria radiata is shaped like a flying white bird and is believed to attract and provide a platform for nectar-feeding pollinators, such as hawk moths. To elucidate the mechanism of lip morphogenesis, we conducted time-lapse imaging of blooming flowers to observe the extension process of the lip and analyzed the cellular morphology during the generation of serrations. We found that the wing part of the lip folds inward in the bud and fully expands in two hours after blooming. The serrations of the lip were initially formed through cell division and later deepened through polar cell elongation. Transcriptome analysis of floral buds revealed the expression of genes involved in floral organ development, cell division, and meiosis. Additionally, genes involved in serration formation are also expressed in floral buds. This study provides insights into the mechanism underlying the formation of the unique lip morphology in Habenaria radiata.", "classifications": [ { "id": "Higaki", "label": "Group Higaki", "parent": "Ueda", "type": "group" }, { "id": "Ueda", "label": "Team Ueda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Seiji", "last_name": "Takeda", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Nishikawa", "name": null }, { "creator_type": "author", "first_name": "Tsutomu", "last_name": "Tachibana", "name": null }, { "creator_type": "author", "first_name": "Takumi", "last_name": "Higaki", "name": null }, { "creator_type": "author", "first_name": "Tomoaki", "last_name": "Sakamoto", "name": null }, { "creator_type": "author", "first_name": "Seisuke", "last_name": "Kimura", "name": null } ], "identifiers": { "doi": { "normalized": "10.3390/plants14030393" }, "pmcid": { "normalized": "PMC11820888" }, "pmid": { "normalized": "39942954" } }, "mesh": [], "publication": { "conference_name": null, "date": "2025 Jan 28", "date_precision": "day", "issue": "3", "normalized_date": "2025-01-28", "pages": "", "proceedings_title": null, "publisher": "", "title": "Plants (Basel, Switzerland)", "volume": "14", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Morphological and Transcriptome Analysis of the Near-Threatened Orchid Habenaria radiata with Petals Shaped Like a Flying White Bird.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yurie", "last_name": "Okayama", "name": null }, { "creator_type": "author", "first_name": "Shin", "last_name": "Ishizawa", "name": null }, { "creator_type": "author", "first_name": "Akane", "last_name": "Aikawa", "name": null }, { "creator_type": "author", "first_name": "Yuko", "last_name": "Nakanishi", "name": null }, { "creator_type": "author", "first_name": "Akio", "last_name": "Uchiyama", "name": null }, { "creator_type": "author", "first_name": "Tomohiko", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/pin.13517" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "39868958" } }, "mesh": [], "publication": { "conference_name": null, "date": "2025 Jan 27", "date_precision": "day", "issue": "", "normalized_date": "2025-01-27", "pages": "", "proceedings_title": null, "publisher": "", "title": "Pathology international", "volume": "", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Myxoid spindle cell tumor with EWSR1-CREM fusion mimicking papillary adenoma of the lung.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Hematopoietic stem cells (HSCs) possess the capacity to regenerate the entire hematopoietic system. However, the precise HSC dynamics in the early post-transplantation phase remain an enigma. Clinically, the initial hematopoiesis in the post-transplantation period is critical, necessitating strategies to accelerate hematopoietic recovery. Here, we uncovered the spatiotemporal dynamics of early active hematopoiesis, \"hematopoietic cell inflation,\" using a highly sensitive in vivo imaging system. Hematopoietic cell inflation occurs in three peaks in the spleen after transplantation, with common myeloid progenitors (CMPs), notably characterized by HSC-like signatures, playing a central role. Leveraging these findings, we developed expanded CMPs (exCMPs), which exhibit a gene expression pattern that selectively proliferates in the spleen and promotes hematopoietic expansion. Moreover, universal exCMPs supported early hematopoiesis in allogeneic transplantation. Human universal exCMPs have the potential to be a viable therapeutic enhancement for all HSC transplant patients.", "classifications": [ { "id": "Kuchimaru", "label": "Group Kuchimaru", "parent": "Shintaku", "type": "group" }, { "id": "Shintaku", "label": "Team Shintaku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Takao", "last_name": "Yogo", "name": null }, { "creator_type": "author", "first_name": "Hans Jiro", "last_name": "Becker", "name": null }, { "creator_type": "author", "first_name": "Takaharu", "last_name": "Kimura", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Iwano", "name": null }, { "creator_type": "author", "first_name": "Takahiro", "last_name": "Kuchimaru", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Miyawaki", "name": null }, { "creator_type": "author", "first_name": "Tomomasa", "last_name": "Yokomizo", "name": null }, { "creator_type": "author", "first_name": "Toshio", "last_name": "Suda", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Iwama", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Yamazaki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.celrep.2025.115241" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "39864058" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Proliferation", "descriptor_ui": "D049109", "major_topic": false }, { "descriptor": "Hematopoiesis", "descriptor_ui": "D006410", "major_topic": true }, { "descriptor": "Hematopoietic Stem Cell Transplantation", "descriptor_ui": "D018380", "major_topic": false }, { "descriptor": "Hematopoietic Stem Cells", "descriptor_ui": "D006412", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Myeloid Progenitor Cells", "descriptor_ui": "D023461", "major_topic": false }, { "descriptor": "Spleen", "descriptor_ui": "D013154", "major_topic": true } ], "publication": { "conference_name": null, "date": "2025 Jan 25", "date_precision": "day", "issue": "2", "normalized_date": "2025-01-25", "pages": "115241", "proceedings_title": null, "publisher": "", "title": "Cell reports", "volume": "44", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Progenitor effect in the spleen drives early recovery via universal hematopoietic cell inflation.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Drug resistance often stems from drug-tolerant persister (DTP) cells in cancer. These cells arise from various lineages and exhibit complex dynamics. However, effectively targeting DTP cells remains challenging. We used single-cell RNA sequencing (scRNA-Seq) data and machine learning (ML) models to identify DTP cells in patient-derived organoids (PDOs) and computationally screened candidate drugs targeting these cells in familial adenomatous polyposis (FAP), associated with a high risk of colorectal cancer. Three PDOs (benign and malignant tumor organoids and a normal organoid) were evaluated using scRNA-Seq. ML models constructed based on public scRNA-Seq data classified DTP versus non-DTP cells. Candidate drugs for DTP cells in a malignant tumor organoid were identified from public drug sensitivity data. From FAP scRNA-Seq data, a specific TC1 cell cluster in tumor organoids was identified. The ML model identified up to 36 % of TC1 cells as DTP cells, a higher proportion than those for other clusters. A viability assay using a malignant tumor organoid demonstrated that YM-155 and THZ2 exert synergistic effects with trametinib. The constructed ML model is effective for DTP cell identification based on scRNA-Seq data for FAP and provides candidate treatments. This approach may improve DTP cell targeting in the treatment of colorectal and other cancers.", "classifications": [ { "id": "JPMJCR2022", "label": "JPMJCR2022", "researcher": "Mutsuhiro Takekawa", "type": "grant" }, { "id": "Suzuki", "label": "Group Suzuki", "parent": "Takekawa", "type": "group" }, { "id": "Takekawa", "label": "Group Takekawa", "parent": "Takekawa", "type": "group" }, { "id": "Takekawa", "label": "Team Takekawa", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yosui", "last_name": "Nojima", "name": null }, { "creator_type": "author", "first_name": "Ryoji", "last_name": "Yao", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Suzuki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.bbadis.2025.167693" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "39870146" } }, "mesh": [ { "descriptor": "Adenomatous Polyposis Coli", "descriptor_ui": "D011125", "major_topic": false }, { "descriptor": "Antineoplastic Agents", "descriptor_ui": "D000970", "major_topic": true }, { "descriptor": "Colorectal Neoplasms", "descriptor_ui": "D015179", "major_topic": true }, { "descriptor": "Drug Resistance, Neoplasm", "descriptor_ui": "D019008", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Machine Learning", "descriptor_ui": "D000069550", "major_topic": true }, { "descriptor": "Organoids", "descriptor_ui": "D009940", "major_topic": false }, { "descriptor": "Pyridones", "descriptor_ui": "D011728", "major_topic": false }, { "descriptor": "Pyrimidinones", "descriptor_ui": "D011744", "major_topic": false }, { "descriptor": "Sequence Analysis, RNA", "descriptor_ui": "D017423", "major_topic": false }, { "descriptor": "Single-Cell Analysis", "descriptor_ui": "D059010", "major_topic": true } ], "publication": { "conference_name": null, "date": "2025 Jan 25", "date_precision": "day", "issue": "", "normalized_date": "2025-01-25", "pages": "167693", "proceedings_title": null, "publisher": "", "title": "Biochimica et biophysica acta. Molecular basis of disease", "volume": "", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Single-cell RNA sequencing and machine learning provide candidate drugs against drug-tolerant persister cells in colorectal cancer.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "INTRODUCTION: Pulmonary high-grade neuroendocrine carcinoma (NEC) includes small cell lung carcinoma (SCLC) and large cell neuroendocrine carcinoma (LCNEC). The seventh and eighth editions of the TNM classification for lung cancer confirmed the applicability of this staging system for SCLC. With the proposal of N2 and M1c subcategories for the ninth edition classification, we assessed the applicability to NECs. METHODS: The database included NEC cases diagnosed between January 2011 and December 2019. Eligible cases, with valid survival time and eighth edition TNM stage, were classified as pure SCLC, combined SCLC/non-small cell carcinoma and LCNEC. Survival was calculated by the Kaplan-Meier method, pairwise differences using log-rank test, and prognostic groups by a Cox regression analysis. RESULTS: There were 6181 pure/combined SCLC and 697 LCNEC cases available. For SCLC, survival outcome analyses included 4453 with clinical stage, and 583 with pathologic stage data. The corresponding numbers for LCNEC were 585 and 508. The SCLC data validated the ninth edition classification for lung cancer, including the proposed new subcategories, N2a, single-station ipsilateral mediastinal/subcarinal lymph node involvement, and N2b, involvement of multiple ipsilateral/subcarinal stations. The data also validated the subcategorization of M1c into M1c1 (multiple lesions in a single extrathoracic organ system) and M1c2 (involvement of multiple extrathoracic organ systems). The LCNEC data were insufficient for complete survival analysis, but the available data showed decreasing survival with increasing clinical and pathological stages. CONCLUSIONS: The ninth edition TNM classification applies to patients with NEC and is the appropriate standard for use in clinical practice.", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Ming Sound", "last_name": "Tsao", "name": null }, { "creator_type": "author", "first_name": "Adam", "last_name": "Rosenthal", "name": null }, { "creator_type": "author", "first_name": "Andrew G.", "last_name": "Nicholson", "name": null }, { "creator_type": "author", "first_name": "Frank", "last_name": "Detterbeck", "name": null }, { "creator_type": "author", "first_name": "Wilfried E. E.", "last_name": "Eberhardt", "name": null }, { "creator_type": "author", "first_name": "Yolande", "last_name": "Lievens", "name": null }, { "creator_type": "author", "first_name": "Eric", "last_name": "Lim", "name": null }, { "creator_type": "author", "first_name": "Jose-Maria", "last_name": "Matilla", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null }, { "creator_type": "author", "first_name": "Pier Luigi", "last_name": "Filosso", "name": null }, { "creator_type": "author", "first_name": "Ricardo", "last_name": "Beyruti", "name": null }, { "creator_type": "author", "first_name": "Katherine K.", "last_name": "Nishimura", "name": null }, { "creator_type": "author", "first_name": "William D.", "last_name": "Travis", "name": null }, { "creator_type": "author", "first_name": "Raymond Uyiosa", "last_name": "Osarogiagbon", "name": null }, { "creator_type": "author", "first_name": "Ramon", "last_name": "Rami-Porta", "name": null }, { "creator_type": "author", "first_name": "Valerie", "last_name": "Rusch", "name": null }, { "creator_type": "author", "first_name": "Hisao", "last_name": "Asamura", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.jtho.2025.01.013" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "39864546" } }, "mesh": [ { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Carcinoma, Large Cell", "descriptor_ui": "D018287", "major_topic": false }, { "descriptor": "Carcinoma, Neuroendocrine", "descriptor_ui": "D018278", "major_topic": true }, { "descriptor": "Databases, Factual", "descriptor_ui": "D016208", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Lung Neoplasms", "descriptor_ui": "D008175", "major_topic": true }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Neoplasm Staging", "descriptor_ui": "D009367", "major_topic": true }, { "descriptor": "Prognosis", "descriptor_ui": "D011379", "major_topic": false }, { "descriptor": "Survival Rate", "descriptor_ui": "D015996", "major_topic": false } ], "publication": { "conference_name": null, "date": "2025 Jan 24", "date_precision": "day", "issue": "", "normalized_date": "2025-01-24", "pages": "S1556-0864(25)00046-2", "proceedings_title": null, "publisher": "", "title": "Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer", "volume": "", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "The International Association for the Study of Lung Cancer Staging Project: The Database and Proposal for the Revision of the Staging of Pulmonary Neuroendocrine Carcinoma in the Forthcoming Ninth Edition of the TNM Classification for Lung Cancer.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Karyotype instability in the germline leads to infertility. Unlike the female germline, the male germline continuously produces fertile sperm throughout life. Here we present a molecular network responsible for maintaining karyotype stability in the male mouse germline. Loss of the cyclin-dependent kinase inhibitor Cdkn1c in undifferentiated spermatogonia induced degeneration of spermatogenesis prior to entry into the differentiating spermatogonia. In vitro analysis of spermatogonial stem cells (SSCs) revealed that CDKN1C localized to spindle microtubules during metaphase, and that disupted microtubule dynamics increased its phosphorylation. Cdkn1c deficiency activated the spindle assembly checkpoint and led to centrosome amplification, premature chromosome segregation, and loss of AURKB, and ultimately TRP53-dependent apoptosis. Trp53-deficient SSCs exhibited karyotype defects, but proliferated normally despite reduced CDKN1C and AURKB expression. In contrast, Aurkb depletion upregulated TRP53 and CDKN1C, suggesting a negative feedback loop to maintain euploidy. Thus, Cdkn1c regulates the male germline karyotype.", "classifications": [ { "id": "Yamamoto", "label": "Group Yamamoto", "parent": "Toyoshima", "type": "group" }, { "id": "Toyoshima", "label": "Team Toyoshima", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Mito", "last_name": "Kanatsu-Shinohara", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Tianjiao", "last_name": "Liu", "name": null }, { "creator_type": "author", "first_name": "Keiichi I.", "last_name": "Nakayama", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Shinohara", "name": null } ], "identifiers": { "doi": { "normalized": "10.1242/dev.204286" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "39850012" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Apoptosis", "descriptor_ui": "D017209", "major_topic": false }, { "descriptor": "Aurora Kinase B", "descriptor_ui": "D064107", "major_topic": false }, { "descriptor": "Germ Cells", "descriptor_ui": "D005854", "major_topic": true }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Spermatogenesis", "descriptor_ui": "D013091", "major_topic": false }, { "descriptor": "Spermatogonia", "descriptor_ui": "D013093", "major_topic": false }, { "descriptor": "Stem Cells", "descriptor_ui": "D013234", "major_topic": true }, { "descriptor": "Tumor Suppressor Protein p53", "descriptor_ui": "D016159", "major_topic": false } ], "publication": { "conference_name": null, "date": "2025 Jan 24", "date_precision": "day", "issue": "", "normalized_date": "2025-01-24", "pages": "dev.204286", "proceedings_title": null, "publisher": "", "title": "Development (Cambridge, England)", "volume": "", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Cdkn1c orchestrates a molecular network that regulates the euploidy of the male mouse germline stem cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Oxidation-reduction (redox) reactions are fundamental to sustaining life, with reactive oxygen and nitrogen species playing pivotal roles in cellular signaling and homeostasis. However, excessive oxidative stress disrupts redox balance, contributing to a wide range of diseases, including inflammatory and pulmonary disorders, neurodegeneration, and cancer. Although numerous antioxidant therapies have been developed and tested for oxidative stress-related diseases, their clinical efficacy remains limited. Here, we introduce the emerging concept of 'supersulfides', a class of redox molecule species with unique antioxidant and nucleophilic properties, which have recently been recognized as crucial regulators of cellular redox homeostasis. Unlike traditional antioxidants, supersulfides offer novel mechanisms of action that directly target the underlying processes of oxidative stress. This review summarizes current knowledge on supersulfides, highlighting their roles in oxidative stress and associated diseases, as well as the mechanisms underlying oxidative stress-related pathology. The therapeutic potential of synthetic supersulfides for treating oxidative stress-related diseases is also discussed. A comprehensive understanding of the molecular and cellular basis of redox biology can help to guide the development of innovative redox-based therapeutic strategies aimed at preventing and treating diseases associated with disturbed redox regulation.", "classifications": [ { "id": "JPMJCR2024", "label": "JPMJCR2024", "researcher": "Motohiro Nishida", "type": "grant" }, { "id": "Akaike", "label": "Group Akaike", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Group Nishida", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yuexuan", "last_name": "Pan", "name": null }, { "creator_type": "author", "first_name": "Tetsuro", "last_name": "Matsunaga", "name": null }, { "creator_type": "author", "first_name": "Tianli", "last_name": "Zhang", "name": null }, { "creator_type": "author", "first_name": "Takaaki", "last_name": "Akaike", "name": null } ], "identifiers": { "doi": { "normalized": "10.3390/biom15020172" }, "pmcid": { "normalized": "PMC11852411" }, "pmid": { "normalized": "40001475" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Antioxidants", "descriptor_ui": "D000975", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Neoplasms", "descriptor_ui": "D009369", "major_topic": false }, { "descriptor": "Oxidation-Reduction", "descriptor_ui": "D010084", "major_topic": false }, { "descriptor": "Oxidative Stress", "descriptor_ui": "D018384", "major_topic": true }, { "descriptor": "Reactive Oxygen Species", "descriptor_ui": "D017382", "major_topic": false }, { "descriptor": "Sulfides", "descriptor_ui": "D013440", "major_topic": true } ], "publication": { "conference_name": null, "date": "2025 Jan 23", "date_precision": "day", "issue": "2", "normalized_date": "2025-01-23", "pages": "", "proceedings_title": null, "publisher": "", "title": "Biomolecules", "volume": "15", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "The Therapeutic Potential of Supersulfides in Oxidative Stress-Related Diseases.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: This study aimed to analyze the functional role of Brd4 in colorectal cancer (CRC) organoids. Brd4 was identified as a CRC-related gene by our previous Sleeping Beauty mutagenesis transposon screening in mice. Brd4 is a transcriptional regulator that recognizes acetylated histones and is known to be involved in inflammatory responses. The role of Brd4 in CRC development remains largely unknown. METHODS: We knocked out Brd4 in tumor organoids carrying mutations in Apc and Kras to generate Brd4KO organoids, and performed RNA-seq. The response of Brd4KO organoids to IFNgamma was analyzed via a cell viability assay, an apoptosis assay, and RNAseq. The results were validated by pharmacological inhibition experiments with JQ1 in human CRC organoids. RESULTS: In Brd4KO organoids, the IFNgamma signaling genes Il33 and Myc target genes were downregulated. The addition of IFNgamma to the colon organoids induced apoptosis, but IFNgamma-induced apoptosis was attenuated in the Brd4KO organoids compared with the control organoids (two-sided t-test, P < 0.05). Similar results were obtained from pharmacological inhibition with JQ1 in human CRC organoids; IL33 expression was decreased, and IFNgamma-induced apoptosis was attenuated in the presence of JQ1. CONCLUSIONS: Our results showed that the inhibition of Brd4 suppressed IFNgamma-induced cytotoxicity by modulating the Jak-Stat pathway. These data suggested that the inhibition of Brd4 could increase cell viability in the cancer microenvironment where IFNgamma is abundant, revealing a new aspect of the molecular mechanism of CRC development. Our results may help in evaluating the application of Bet inhibitors in treating CRC. Additionally, our RNA-seq data sets will be helpful for clarifying the relationship between Brd4 and immunomodulators, such as Il33, or for studying the responses of colonic epithelial cells to IFNgamma.", "classifications": [ { "id": "Okamoto", "label": "Group Okamoto", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Akimi", "last_name": "Yonezawa", "name": null }, { "creator_type": "author", "first_name": "Kana", "last_name": "Shimomura", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Okamoto", "name": null }, { "creator_type": "author", "first_name": "Haruna", "last_name": "Takeda", "name": null } ], "identifiers": { "doi": { "normalized": "10.1186/s12885-025-13544-y" }, "pmcid": { "normalized": "PMC11759431" }, "pmid": { "normalized": "39849410" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Apoptosis", "descriptor_ui": "D017209", "major_topic": true }, { "descriptor": "Azepines", "descriptor_ui": "D001381", "major_topic": false }, { "descriptor": "Bromodomain Containing Proteins", "descriptor_ui": "D000092468", "major_topic": false }, { "descriptor": "Cell Cycle Proteins", "descriptor_ui": "D018797", "major_topic": true }, { "descriptor": "Colorectal Neoplasms", "descriptor_ui": "D015179", "major_topic": true }, { "descriptor": "Gene Expression Regulation, Neoplastic", "descriptor_ui": "D015972", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Interferon-gamma", "descriptor_ui": "D007371", "major_topic": true }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Organoids", "descriptor_ui": "D009940", "major_topic": true }, { "descriptor": "Transcription Factors", "descriptor_ui": "D014157", "major_topic": true }, { "descriptor": "Triazoles", "descriptor_ui": "D014230", "major_topic": false } ], "publication": { "conference_name": null, "date": "2025 Jan 23", "date_precision": "day", "issue": "1", "normalized_date": "2025-01-23", "pages": "136", "proceedings_title": null, "publisher": "", "title": "BMC cancer", "volume": "25", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Inhibition of BRD4 attenuated IFNgamma-induced apoptosis in colorectal cancer organoids.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The synthesis and characterization of fused aromatic networks composed of zinc tetrapyrazinoporphyrazines are reported. The steric repulsion of bulky substituents induced the formation of three-dimensional structures. Thus-obtained insoluble polymers adsorbed CO(2) and had near-infrared absorption indicating their porosity and extended pi-conjugation.", "classifications": [ { "id": "Hijikata", "label": "Group Hijikata", "parent": "Tsuchiya", "type": "group" }, { "id": "Tsuchiya", "label": "Team Tsuchiya", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Kosuke", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Teruki", "last_name": "Toya", "name": null }, { "creator_type": "author", "first_name": "Yuto", "last_name": "Toyota", "name": null }, { "creator_type": "author", "first_name": "Yoichi", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Junichi", "last_name": "Usuba", "name": null }, { "creator_type": "author", "first_name": "Yuh", "last_name": "Hijikata", "name": null }, { "creator_type": "author", "first_name": "Ryotaro", "last_name": "Matsuda", "name": null }, { "creator_type": "author", "first_name": "Katsuyuki", "last_name": "Nishimura", "name": null }, { "creator_type": "author", "first_name": "Haruki", "last_name": "Sugiyama", "name": null }, { "creator_type": "author", "first_name": "Yasutomo", "last_name": "Segawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1039/d4cc06293k" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "39838903" } }, "mesh": [], "publication": { "conference_name": null, "date": "2025 Jan 22", "date_precision": "day", "issue": "", "normalized_date": "2025-01-22", "pages": "", "proceedings_title": null, "publisher": "", "title": "Chemical communications (Cambridge, England)", "volume": "", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Synthesis of fully fused tetrapyrazinoporphyrazine polymers bearing three-dimensional structures controlled by steric repulsion.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "N-heterocyclic carbene (NHC)-protected gold nanoclusters display high stability and high photoluminescence, making them well-suited for fluorescence imaging and photodynamic therapeutic applications. We report herein the synthesis of two bisNHC-protected Au(13) nanoclusters with pi-extended aromatic systems. Depending on the position of the pi-extended aromatic system, changes to the structure of the ligand shell in the cluster are observed, with the ability to correlate increases in rigidity with increases in fluorescence quantum yield. Density functional theory analysis reveals that both synthesized Au(13) nanoclusters are 8-electron superatoms but have distinct differences in the characteristics of the lowest unoccupied single-electron states. Qualitatively, this implies different mechanisms for excitations and their decay over the fundamental energy gap. Stability and photophysical studies were carried out to provide the emission lifetime and optical purity of the two clusters. Active intracellular uptake of the nanoclusters was confirmed in vitro using confocal microscopy in human epithelial carcinoma cells. Reactive oxygen species production was measured at 7% efficiency. The high cluster stability, photoluminescence quantum yields, and efficient cellular uptake in cancer cells suggest potential for these nanoclusters as highly efficient and tunable nanomedical platforms.", "classifications": [ { "id": "Nanbo", "label": "Group Nanbo", "parent": "Tsuchiya", "type": "group" }, { "id": "Tsuchiya", "label": "Team Tsuchiya", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Viveka K.", "last_name": "Kulkarni", "name": null }, { "creator_type": "author", "first_name": "Emily L.", "last_name": "Albright", "name": null }, { "creator_type": "author", "first_name": "Elham", "last_name": "Zeinizade", "name": null }, { "creator_type": "author", "first_name": "Emily", "last_name": "Steele", "name": null }, { "creator_type": "author", "first_name": "Juan", "last_name": "Chen", "name": null }, { "creator_type": "author", "first_name": "Lili", "last_name": "Ding", "name": null }, { "creator_type": "author", "first_name": "Sami", "last_name": "Malola", "name": null }, { "creator_type": "author", "first_name": "Shinjiro", "last_name": "Takano", "name": null }, { "creator_type": "author", "first_name": "Kristen", "last_name": "Harrington", "name": null }, { "creator_type": "author", "first_name": "Nahyun", "last_name": "Kwon", "name": null }, { "creator_type": "author", "first_name": "Tetyana I.", "last_name": "Levchenko", "name": null }, { "creator_type": "author", "first_name": "Masakazu", "last_name": "Nambo", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Tsukuda", "name": null }, { "creator_type": "author", "first_name": "Hannu", "last_name": "Hakkinen", "name": null }, { "creator_type": "author", "first_name": "Kevin", "last_name": "Stamplecoskie", "name": null }, { "creator_type": "author", "first_name": "Gang", "last_name": "Zheng", "name": null }, { "creator_type": "author", "first_name": "Cathleen M.", "last_name": "Crudden", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/jacs.4c12072" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "39841867" } }, "mesh": [ { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Density Functional Theory", "descriptor_ui": "D000077318", "major_topic": false }, { "descriptor": "Gold", "descriptor_ui": "D006046", "major_topic": true }, { "descriptor": "Heterocyclic Compounds", "descriptor_ui": "D006571", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Ligands", "descriptor_ui": "D008024", "major_topic": false }, { "descriptor": "Metal Nanoparticles", "descriptor_ui": "D053768", "major_topic": true }, { "descriptor": "Methane", "descriptor_ui": "D008697", "major_topic": true }, { "descriptor": "Molecular Structure", "descriptor_ui": "D015394", "major_topic": false }, { "descriptor": "Reactive Oxygen Species", "descriptor_ui": "D017382", "major_topic": false } ], "publication": { "conference_name": null, "date": "2025 Jan 22", "date_precision": "day", "issue": "", "normalized_date": "2025-01-22", "pages": "", "proceedings_title": null, "publisher": "", "title": "Journal of the American Chemical Society", "volume": "", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Impact of Ligand Structure on Biological Activity and Photophysical Properties of NHC-Protected Au(13) Nanoclusters.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Placebo analgesia is caused by inactive treatment, implicating endogenous brain function involvement. However, the neurobiological basis remains unclear. In this study, we found that mu-opioid signals in the medial prefrontal cortex (mPFC) activate the descending pain inhibitory system to initiate placebo analgesia in neuropathic pain rats. Chemogenetic manipulation demonstrated that specific activation of mu-opioid receptor-positive (MOR(+)) neurons in the mPFC or suppression of the mPFC-ventrolateral periaqueductal gray (vlPAG) circuit inhibited placebo analgesia in rats. MOR(+) neurons in the mPFC are monosynaptically connected and directly inhibit layer V pyramidal neurons that project to the vlPAG via GABA(A) receptors. Thus, intrinsic opioid signaling in the mPFC disinhibits excitatory outflow to the vlPAG by suppressing MOR(+) neurons, leading to descending pain inhibitory system activation that initiates placebo analgesia. Our results shed light on the fundamental neurobiological mechanism of the placebo effect that maximizes therapeutic efficacy and reduces adverse drug effects in medical practice.", "classifications": [ { "id": "Miyamichi", "label": "Group Miyamichi", "parent": "Enomoto", "type": "group" }, { "id": "Enomoto", "label": "Team Enomoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Neyama", "name": null }, { "creator_type": "author", "first_name": "Yuping", "last_name": "Wu", "name": null }, { "creator_type": "author", "first_name": "Yuka", "last_name": "Nakaya", "name": null }, { "creator_type": "author", "first_name": "Shigeki", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Tomoko", "last_name": "Shimizu", "name": null }, { "creator_type": "author", "first_name": "Tsuyoshi", "last_name": "Tahara", "name": null }, { "creator_type": "author", "first_name": "Mika", "last_name": "Shigeta", "name": null }, { "creator_type": "author", "first_name": "Michiko", "last_name": "Inoue", "name": null }, { "creator_type": "author", "first_name": "Kazunari", "last_name": "Miyamichi", "name": null }, { "creator_type": "author", "first_name": "Natsuki", "last_name": "Matsushita", "name": null }, { "creator_type": "author", "first_name": "Tomoji", "last_name": "Mashimo", "name": null }, { "creator_type": "author", "first_name": "Yoshiki", "last_name": "Miyasaka", "name": null }, { "creator_type": "author", "first_name": "Yi", "last_name": "Dai", "name": null }, { "creator_type": "author", "first_name": "Koichi", "last_name": "Noguchi", "name": null }, { "creator_type": "author", "first_name": "Yasuyoshi", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Masayuki", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Kazuto", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Yilong", "last_name": "Cui", "name": null } ], "identifiers": { "doi": { "normalized": "10.1126/sciadv.adp8494" }, "pmcid": { "normalized": "PMC11734720" }, "pmid": { "normalized": "39813331" } }, "mesh": [ { "descriptor": "Analgesia", "descriptor_ui": "D000698", "major_topic": true }, { "descriptor": "Analgesics, Opioid", "descriptor_ui": "D000701", "major_topic": true }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Neuralgia", "descriptor_ui": "D009437", "major_topic": true }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Pain", "descriptor_ui": "D010146", "major_topic": true }, { "descriptor": "Periaqueductal Gray", "descriptor_ui": "D010487", "major_topic": false }, { "descriptor": "Placebo Effect", "descriptor_ui": "D015990", "major_topic": false }, { "descriptor": "Prefrontal Cortex", "descriptor_ui": "D017397", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Rats, Sprague-Dawley", "descriptor_ui": "D017207", "major_topic": false }, { "descriptor": "Receptors, Opioid, mu", "descriptor_ui": "D017450", "major_topic": true } ], "publication": { "conference_name": null, "date": "2025 Jan 17", "date_precision": "day", "issue": "3", "normalized_date": "2025-01-17", "pages": "eadp8494", "proceedings_title": null, "publisher": "", "title": "Science advances", "volume": "11", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Opioidergic activation of the descending pain inhibitory system underlies placebo analgesia.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "We develop a data harmonization approach for C. elegans volumetric microscopy data, consisting of a standardized format, pre-processing techniques, and human-in-the-loop machine-learning-based analysis tools. Using this approach, we unify a diverse collection of 118 whole-brain neural activity imaging datasets from five labs, storing these and accompanying tools in an online repository WormID (wormid.org). With this repository, we train three existing automated cell-identification algorithms, CPD, StatAtlas, and CRF_ID, to enable accuracy that generalizes across labs, recovering all human-labeled neurons in some cases. We mine this repository to identify factors that influence the developmental positioning of neurons. This growing resource of data, code, apps, and tutorials enables users to (1) study neuroanatomical organization and neural activity across diverse experimental paradigms, (2) develop and benchmark algorithms for automated neuron detection, segmentation, cell identification, tracking, and activity extraction, and (3) share data with the community and comply with data-sharing policies.", "classifications": [ { "id": "Onami", "label": "Group Onami", "parent": "Fujiwara", "type": "group" }, { "id": "Fujiwara", "label": "Team Fujiwara", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Daniel Y.", "last_name": "Sprague", "name": null }, { "creator_type": "author", "first_name": "Kevin", "last_name": "Rusch", "name": null }, { "creator_type": "author", "first_name": "Raymond L.", "last_name": "Dunn", "name": null }, { "creator_type": "author", "first_name": "Jackson M.", "last_name": "Borchardt", "name": null }, { "creator_type": "author", "first_name": "Steven", "last_name": "Ban", "name": null }, { "creator_type": "author", "first_name": "Greg", "last_name": "Bubnis", "name": null }, { "creator_type": "author", "first_name": "Grace C.", "last_name": "Chiu", "name": null }, { "creator_type": "author", "first_name": "Chentao", "last_name": "Wen", "name": null }, { "creator_type": "author", "first_name": "Ryoga", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Shivesh", "last_name": "Chaudhary", "name": null }, { "creator_type": "author", "first_name": "Hyun Jee", "last_name": "Lee", "name": null }, { "creator_type": "author", "first_name": "Zikai", "last_name": "Yu", "name": null }, { "creator_type": "author", "first_name": "Benjamin", "last_name": "Dichter", "name": null }, { "creator_type": "author", "first_name": "Ryan", "last_name": "Ly", "name": null }, { "creator_type": "author", "first_name": "Shuichi", "last_name": "Onami", "name": null }, { "creator_type": "author", "first_name": "Hang", "last_name": "Lu", "name": null }, { "creator_type": "author", "first_name": "Koutarou D.", "last_name": "Kimura", "name": null }, { "creator_type": "author", "first_name": "Eviatar", "last_name": "Yemini", "name": null }, { "creator_type": "author", "first_name": "Saul", "last_name": "Kato", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.crmeth.2024.100964" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "39826553" } }, "mesh": [ { "descriptor": "Algorithms", "descriptor_ui": "D000465", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Brain", "descriptor_ui": "D001921", "major_topic": true }, { "descriptor": "Caenorhabditis elegans", "descriptor_ui": "D017173", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Image Processing, Computer-Assisted", "descriptor_ui": "D007091", "major_topic": false }, { "descriptor": "Machine Learning", "descriptor_ui": "D000069550", "major_topic": false }, { "descriptor": "Neuroimaging", "descriptor_ui": "D059906", "major_topic": true }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": true } ], "publication": { "conference_name": null, "date": "2025 Jan 15", "date_precision": "day", "issue": "", "normalized_date": "2025-01-15", "pages": "100964", "proceedings_title": null, "publisher": "", "title": "Cell reports methods", "volume": "", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Unifying community whole-brain imaging datasets enables robust neuron identification and reveals determinants of neuron position in C. elegans.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Ultrasound (US) imaging is a widely used tool in oncology because of its noninvasiveness and real-time performance. However, its diagnostic accuracy can be limited by the skills of the examiner when performing manual scanning and by the presence of acoustic shadows that degrade image quality. Artificial intelligence (AI) technologies can support examiners in cancer screening and diagnosis by addressing these limitations. Here, we examine recent advances in AI research and development for US imaging in oncology. Breast cancer has been the most extensively studied cancer, with research predominantly focusing on tumor detection, differentiation between benign and malignant lesions, and prediction of lymph node metastasis. The American College of Radiology developed a medical imaging reporting and data system for various cancers that is often used to evaluate the accuracy of AI models. We will also explore the application of AI in clinical settings for US imaging in oncology. Despite progress, the number of approved AI-equipped software as medical devices for US imaging remains limited in Japan, the United States, and Europe. Practical issues that need to be addressed for clinical application include domain shifts, black boxes, and acoustic shadows. To address these issues, advances in image quality control, AI explainability, and preprocessing of acoustic shadows are essential.", "classifications": [ { "id": "Hamamoto", "label": "Group Hamamoto", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Masaaki", "last_name": "Komatsu", "name": null }, { "creator_type": "author", "first_name": "Naoki", "last_name": "Teraya", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Natsume", "name": null }, { "creator_type": "author", "first_name": "Naoaki", "last_name": "Harada", "name": null }, { "creator_type": "author", "first_name": "Katsuji", "last_name": "Takeda", "name": null }, { "creator_type": "author", "first_name": "Ryuji", "last_name": "Hamamoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.31662/jmaj.2024-0203" }, "pmcid": { "normalized": "PMC11799696" }, "pmid": { "normalized": "39926099" } }, "mesh": [], "publication": { "conference_name": null, "date": "2025 Jan 15", "date_precision": "day", "issue": "1", "normalized_date": "2025-01-15", "pages": "18-25", "proceedings_title": null, "publisher": "", "title": "JMA journal", "volume": "8", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Clinical Application of Artificial Intelligence in Ultrasound Imaging for Oncology.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: Perivascular epithelioid cell tumors (PEComas) rarely appear in the head and neck region. This case report describes two transcription factor E3 (TFE3)-rearranged PEComa cases, consisting of one in the orbit and one in the nasal cavity. CASE PRESENTATION: Both cases demonstrated sheet-like or focal nested architecture and comprised epithelioid cells with abundant clear to eosinophilic cytoplasm and vascular stroma. The first case exhibited partial pleomorphism, a small necrosis area, and slightly increased mitosis and was classified as malignant. The second case demonstrated mild atypia and no mitosis or necrosis and was categorized as benign. The nasal tumor was initially considered a TFE3-rearranged renal cell carcinoma metastasis. However, a subsequent renal tumor biopsy revealed angiomyolipoma. The RNA sequence revealed ZC3H4::TFE3 and PRCC::TFE3 fusions in the first and second cases, respectively. CONCLUSION: The fusion partner gene ZC3H4 is uncommon, and this is the third reported PEComa case. The fusion partner gene PRCC is often reported in TFE3-rearranged renal cell carcinoma, and this PEComa case is the second reported in the head and neck region. The initially reported cases with the fusion partner genes ZC3H4 and PRCC were categorized as malignant. These cases were discussed with a literature review.", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yuka", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Akihiko", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Seiichi", "last_name": "Yoshimoto", "name": null }, { "creator_type": "author", "first_name": "Shigenobu", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Satsuki", "last_name": "Kishikawa", "name": null }, { "creator_type": "author", "first_name": "Ayaka", "last_name": "Mitsui", "name": null }, { "creator_type": "author", "first_name": "Eijitsu", "last_name": "Ryo", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Kojima", "name": null }, { "creator_type": "author", "first_name": "Kan", "last_name": "Yonemori", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null }, { "creator_type": "author", "first_name": "Taisuke", "last_name": "Mori", "name": null } ], "identifiers": { "doi": { "normalized": "10.1186/s13000-025-01602-9" }, "pmcid": { "normalized": "PMC11734225" }, "pmid": { "normalized": "39815310" } }, "mesh": [ { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Basic Helix-Loop-Helix Leucine Zipper Transcription Factors", "descriptor_ui": "D051778", "major_topic": true }, { "descriptor": "Biomarkers, Tumor", "descriptor_ui": "D014408", "major_topic": false }, { "descriptor": "Cell Cycle Proteins", "descriptor_ui": "D018797", "major_topic": false }, { "descriptor": "Diagnosis, Differential", "descriptor_ui": "D003937", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Gene Fusion", "descriptor_ui": "D050939", "major_topic": false }, { "descriptor": "Gene Rearrangement", "descriptor_ui": "D015321", "major_topic": true }, { "descriptor": "Head and Neck Neoplasms", "descriptor_ui": "D006258", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Neoplasm Proteins", "descriptor_ui": "D009363", "major_topic": false }, { "descriptor": "Perivascular Epithelioid Cell Neoplasms", "descriptor_ui": "D054973", "major_topic": true } ], "publication": { "conference_name": null, "date": "2025 Jan 15", "date_precision": "day", "issue": "1", "normalized_date": "2025-01-15", "pages": "7", "proceedings_title": null, "publisher": "", "title": "Diagnostic pathology", "volume": "20", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "TFE3-rearranged perivascular epithelioid cell tumors of the head and neck with rare fusion partners: clues to the differential diagnosis between benign and malignant tumors.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "In mammals, lactation is essential for the health and growth of infants and supports the formation of the mother-infant bond. Breastfeeding is mediated by the neurohormone oxytocin (OT), which is released into the bloodstream in a pulsatile manner from OT neurons in the hypothalamus to promote milk ejection into mammary ducts. While classical studies using anesthetized rats have illuminated the activity patterns of putative OT neurons during breastfeeding, the molecular, cellular, and neural circuit mechanisms driving the synchronous pulsatile bursts of OT neurons in response to nipple stimulation remain largely elusive. Only recently have molecular neuroscience techniques for imaging and manipulating specific genetically defined cells been applied to lactating mice. For instance, fiber photometry has revealed the temporal dynamics of the population pulsatile activity of OT neurons in freely moving dams across various lactation stages, while microendoscopy has provided single-cell level insights. In this review, we introduce the neuroscience of lactation with respect to OT neuron activity, discuss findings from molecular neuroscience approaches, and highlight key unresolved questions.", "classifications": [ { "id": "Miyamichi", "label": "Group Miyamichi", "parent": "Enomoto", "type": "group" }, { "id": "Enomoto", "label": "Team Enomoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Hiroko", "last_name": "Yukinaga", "name": null }, { "creator_type": "author", "first_name": "Kazunari", "last_name": "Miyamichi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.neures.2025.01.002" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "39824310" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Lactation", "descriptor_ui": "D007774", "major_topic": true }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": true }, { "descriptor": "Oxytocin", "descriptor_ui": "D010121", "major_topic": true } ], "publication": { "conference_name": null, "date": "2025 Jan 15", "date_precision": "day", "issue": "", "normalized_date": "2025-01-15", "pages": "S0168-0102(25)00012-4", "proceedings_title": null, "publisher": "", "title": "Neuroscience research", "volume": "", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Oxytocin and Neuroscience of Lactation: Insights from the Molecular Genetic Approach.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Hepatic de novo lipogenesis (DNL) is increased by both carbohydrate intake and protein consumption. In hepatic fat synthesis, a key role is played by the induction of the hepatic expression of lipogenic genes, including Fasn, Scd1, and Srebf1. Regarding carbohydrate intake, increased blood glucose and insulin levels promote the expression of hepatic lipogenic genes. However, although amino acids serve as a carbon source for hepatic DNL during protein consumption, their effects on hepatic lipogenic gene expression remain unclear. We investigated the effects of amino acids on hepatic lipogenic gene induction using primary cultured mouse hepatocytes and hepatic Fasn reporter (l-FasnGLuc) mice. In primary cultured hepatocytes, lipogenic gene expression (Fasn, Scd1, Srebf1) was induced under postprandial-mimicking conditions (treatment with insulin and LXR agonist). When hepatocytes were stimulated with an amino acid mixture containing 20 amino acids, the induction of lipogenic gene expression was enhanced, but this effect disappeared when proline was removed from the mixture. Furthermore, when each amino acid was tested individually, only proline potentiated the induction of lipogenic gene expression in hepatocytes under postprandial-mimicking conditions. In mouse liver, continuous proline infusion via osmotic pump increased Fasn gene expression and showed a trend toward increased Srebf1 expression. In l-FasnGLuc mice, continuous proline infusion resulted in sustained enhancement of hepatic Fasn transcription, measured by secreted luciferase activity. These results demonstrate that proline enhances the induction of hepatic lipogenic gene expression both in vitro and in vivo.", "classifications": [ { "id": "JPMJCR2123", "label": "JPMJCR2123", "researcher": "Shinya Kuroda", "type": "grant" }, { "id": "Inaba", "label": "Group Inaba", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Group Kuroda", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Akinori", "last_name": "Taniguchi", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Kumi", "last_name": "Kimura", "name": null }, { "creator_type": "author", "first_name": "Emi", "last_name": "Hashiuchi", "name": null }, { "creator_type": "author", "first_name": "Nami", "last_name": "Ohashi", "name": null }, { "creator_type": "author", "first_name": "Hirofumi", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Mashito", "last_name": "Sakai", "name": null }, { "creator_type": "author", "first_name": "Michihiro", "last_name": "Matsumoto", "name": null }, { "creator_type": "author", "first_name": "Shun-Ichiro", "last_name": "Asahara", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Inoue", "name": null }, { "creator_type": "author", "first_name": "Yuka", "last_name": "Inaba", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.bbrc.2025.151314" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "39799864" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Fatty Acid Synthase, Type I", "descriptor_ui": "D054890", "major_topic": true }, { "descriptor": "Genes, Reporter", "descriptor_ui": "D017930", "major_topic": false }, { "descriptor": "Hepatocytes", "descriptor_ui": "D022781", "major_topic": false }, { "descriptor": "Lipogenesis", "descriptor_ui": "D050155", "major_topic": true }, { "descriptor": "Liver", "descriptor_ui": "D008099", "major_topic": true }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Proline", "descriptor_ui": "D011392", "major_topic": true }, { "descriptor": "Stearoyl-CoA Desaturase", "descriptor_ui": "D013230", "major_topic": false }, { "descriptor": "Sterol Regulatory Element Binding Protein 1", "descriptor_ui": "D051780", "major_topic": false } ], "publication": { "conference_name": null, "date": "2025 Jan 9", "date_precision": "day", "issue": "", "normalized_date": "2025-01-09", "pages": "151314", "proceedings_title": null, "publisher": "", "title": "Biochemical and biophysical research communications", "volume": "747", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Proline enhances the hepatic induction of lipogenic gene expression in male hepatic fasn reporter mice.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: Our human volumetric MRI study (Dai et al., 2024) demonstrated that habenula (Hb) volume is associated with psychological resilience, a key protective factor against depression. However, the biological mechanisms underpinning this relationship remain unclear. A recent animal study highlighted that neuronal activity in the Hb modulates rapid eye movement (REM) sleep, influencing depressive behaviors during wakefulness. Based on this, we hypothesized that sleep quality mediates the relationship between Hb volume and psychological resilience in humans. METHODS: We utilized a deep learning-based automated segmentation model to estimate Hb volume from 3T-MRI T1-weighted images of 84 healthy participants. Correlation analyses were performed to examine the relationship between Hb volume and questionnaire-based assessments of sleep quality. Mediation analysis was then conducted with Hb volume as the independent variable, psychological resilience as the dependent variable, and sleep quality as the mediator. RESULTS: Hb volume was found to be negatively correlated with sleep disturbance, indicating that individuals with larger Hb volumes experienced better sleep quality. A lateralization effect was also observed, where greater leftward asymmetry (larger left Hb volume compared to right) was associated with more severe sleep disturbances. Moreover, sleep quality was identified as a mediator in the relationship between Hb volume and psychological resilience. CONCLUSION: This study provides preliminary evidence of the association among Hb volume, sleep quality, and resilience. Sleep quality appears to be a critical mediator in the biological processes linking smaller Hb volumes to decreased psychological resilience. Enhancing sleep quality may be a promising approach for bolstering psychological resilience and reducing the risk of depression.", "classifications": [ { "id": "Fujiwara", "label": "Group Fujiwara", "parent": "Fujiwara", "type": "group" }, { "id": "Fujiwara", "label": "Team Fujiwara", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Qi", "last_name": "Dai", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Kyuragi", "name": null }, { "creator_type": "author", "first_name": "Halwa", "last_name": "Zakia", "name": null }, { "creator_type": "author", "first_name": "Naoya", "last_name": "Oishi", "name": null }, { "creator_type": "author", "first_name": "Lichang", "last_name": "Yao", "name": null }, { "creator_type": "author", "first_name": "Morio", "last_name": "Aki", "name": null }, { "creator_type": "author", "first_name": "Mami", "last_name": "Shibata", "name": null }, { "creator_type": "author", "first_name": "Zhilin", "last_name": "Zhang", "name": null }, { "creator_type": "author", "first_name": "Luyao", "last_name": "Wang", "name": null }, { "creator_type": "author", "first_name": "Jiajia", "last_name": "Yang", "name": null }, { "creator_type": "author", "first_name": "Toshiya", "last_name": "Murai", "name": null }, { "creator_type": "author", "first_name": "Hironobu", "last_name": "Fujiwara", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.psychres.2025.116358" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "39799818" } }, "mesh": [ { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Deep Learning", "descriptor_ui": "D000077321", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Habenula", "descriptor_ui": "D019262", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Magnetic Resonance Imaging", "descriptor_ui": "D008279", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Resilience, Psychological", "descriptor_ui": "D055500", "major_topic": true }, { "descriptor": "Sleep Quality", "descriptor_ui": "D000089943", "major_topic": true }, { "descriptor": "Sleep Wake Disorders", "descriptor_ui": "D012893", "major_topic": true }, { "descriptor": "Young Adult", "descriptor_ui": "D055815", "major_topic": false } ], "publication": { "conference_name": null, "date": "2025 Jan 9", "date_precision": "day", "issue": "", "normalized_date": "2025-01-09", "pages": "116358", "proceedings_title": null, "publisher": "", "title": "Psychiatry research", "volume": "344", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "The role of sleep quality in mediating the relationship between habenula volume and resilience.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Genomic variants causing abnormal splicing play important roles in genetic disorders and cancer development. Among them, variants that cause the formation of novel splice-sites (splice-site creating variants, SSCVs) are particularly difficult to identify and often overlooked in genomic studies. Additionally, these SSCVs are frequently considered promising candidates for treatment with splice-switching antisense oligonucleotides (ASOs). To leverage massive transcriptome sequence data such as those available from the Sequence Read Archive, we develop a novel framework to screen for SSCVs solely using transcriptome data. We apply it to 322,072 publicly available transcriptomes and identify 30,130 SSCVs. Among them, 5121 SSCVs affect disease-causing variants. By utilizing this extensive collection of SSCVs, we reveal the characteristics of Alu exonization via SSCVs, especially the hotspots of SSCVs within Alu sequences and their evolutionary relationships. We discover novel gain-of-function SSCVs in the deep intronic region of the NOTCH1 gene and demonstrate that their activation can be suppressed using splice-switching ASOs. Collectively, we provide a systematic approach for automatically acquiring a registry of SSCVs, which facilitates the elucidation of novel biological mechanisms underlying splicing and serves as a valuable resource for drug discovery. The catalogs of SSCVs identified in this study are accessible on the SSCV DB ( https://sscvdb.io ).", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Naoko", "last_name": "Iida", "name": null }, { "creator_type": "author", "first_name": "Ai", "last_name": "Okada", "name": null }, { "creator_type": "author", "first_name": "Yoshihisa", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Kenichi", "last_name": "Chiba", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null }, { "creator_type": "author", "first_name": "Yuichi", "last_name": "Shiraishi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41467-024-55185-y" }, "pmcid": { "normalized": "PMC11718197" }, "pmid": { "normalized": "39788962" } }, "mesh": [ { "descriptor": "Alternative Splicing", "descriptor_ui": "D017398", "major_topic": false }, { "descriptor": "Alu Elements", "descriptor_ui": "D020087", "major_topic": true }, { "descriptor": "Exons", "descriptor_ui": "D005091", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Introns", "descriptor_ui": "D007438", "major_topic": false }, { "descriptor": "Oligonucleotides, Antisense", "descriptor_ui": "D016376", "major_topic": false }, { "descriptor": "Receptor, Notch1", "descriptor_ui": "D051881", "major_topic": false }, { "descriptor": "Registries", "descriptor_ui": "D012042", "major_topic": false }, { "descriptor": "RNA Splice Sites", "descriptor_ui": "D022821", "major_topic": true }, { "descriptor": "RNA Splicing", "descriptor_ui": "D012326", "major_topic": true }, { "descriptor": "Transcriptome", "descriptor_ui": "D059467", "major_topic": true } ], "publication": { "conference_name": null, "date": "2025 Jan 9", "date_precision": "day", "issue": "1", "normalized_date": "2025-01-09", "pages": "426", "proceedings_title": null, "publisher": "", "title": "Nature communications", "volume": "16", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Systematically developing a registry of splice-site creating variants utilizing massive publicly available transcriptome sequence data.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Vulvar adenocarcinoma of the intestinal type (VAIt) is a rare subtype of primary vulvar carcinoma, with approximately 30 cases documented in the English literature. This study presents 2 new cases of HPV-independent VAIt with lymph node metastasis and discusses their clinical presentation, histopathologic features, and whole exome sequencing (WES) analysis. Both cases exhibited histologic features consistent with VAIt, including tubular, papillary, and mucinous carcinoma components. Immunohistochemical analysis showed p16 patchy staining, CDX2, CK20, and SATB2 positivity, while being negative for ER, PAX8, and CK7. WES revealed pathogenic TP53 mutations in both cases, accompanied by distinct additional mutations (GRIN2A and KDM6A in Case #1; CHD4 in Case #2). Common copy number alterations (CNAs) included TP53 loss of heterozygosity and CD274/PD-L1 amplification. However, other CNAs varied between the cases. Immunohistochemistry for p53 suggests the presence of both wild-type and mutant subclones, indicating that TP53 abnormalities may be acquired during tumor progression. Both tumors showed mutational signatures SBS1 and SBS5, associated with aging and DNA damage. Our findings deepen the understanding of the genetic events involved in the tumorigenesis of HPV-independent VAIt. Given the TP53 abnormalities and CD274/PD-L1 amplification, emerging p53-based therapies and immune checkpoint inhibitors may represent potential treatment targets. While these findings contribute to the understanding of VAIt tumorigenesis, further research is required to validate these observations in a larger cohort.", "classifications": [ { "id": "Hamamoto", "label": "Group Hamamoto", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Erisa", "last_name": "Fujii", "name": null }, { "creator_type": "author", "first_name": "Mayumi Kobayashi", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Hanako", "last_name": "Ono", "name": null }, { "creator_type": "author", "first_name": "Maiko", "last_name": "Yamaguchi", "name": null }, { "creator_type": "author", "first_name": "Daiki", "last_name": "Higuchi", "name": null }, { "creator_type": "author", "first_name": "Takafumi", "last_name": "Koyama", "name": null }, { "creator_type": "author", "first_name": "Masaaki", "last_name": "Komatsu", "name": null }, { "creator_type": "author", "first_name": "Ryuji", "last_name": "Hamamoto", "name": null }, { "creator_type": "author", "first_name": "Mitsuya", "last_name": "Ishikawa", "name": null }, { "creator_type": "author", "first_name": "Tomoyasu", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Kohno", "name": null }, { "creator_type": "author", "first_name": "Kouya", "last_name": "Shiraishi", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Yoshida", "name": null } ], "identifiers": { "doi": { "normalized": "10.1097/pgp.0000000000001093" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "39868745" } }, "mesh": [ { "descriptor": "Adenocarcinoma", "descriptor_ui": "D000230", "major_topic": true }, { "descriptor": "B7-H1 Antigen", "descriptor_ui": "D060890", "major_topic": true }, { "descriptor": "DNA Copy Number Variations", "descriptor_ui": "D056915", "major_topic": false }, { "descriptor": "Exome Sequencing", "descriptor_ui": "D000073359", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Gene Amplification", "descriptor_ui": "D005784", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": false }, { "descriptor": "Tumor Suppressor Protein p53", "descriptor_ui": "D016159", "major_topic": true }, { "descriptor": "Vulvar Neoplasms", "descriptor_ui": "D014846", "major_topic": true } ], "publication": { "conference_name": null, "date": "2025 Jan 9", "date_precision": "day", "issue": "", "normalized_date": "2025-01-09", "pages": "", "proceedings_title": null, "publisher": "", "title": "International journal of gynecological pathology : official journal of the International Society of Gynecological Pathologists", "volume": "", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "TP53 Mutations and PD-L1 Amplification in Vulvar Adenocarcinoma of the Intestinal Type: Insights From Whole Exome Sequencing of 2 Cases.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "From September 16 to 19, 2024, an international symposium to celebrate the centennial of the discovery of the gastrula organizer by Hans Spemann and Hilde Mangold, was held at the University of Freiburg, Germany, where they studied embryology. There were 41 plenary lectures, 11 short talks, and 182 poster presentations, with more than 300 participants from 23 countries. The symposium covered research topics broadly related to developmental, cell, genome, and evolutionary biology, mainly focused on early animal development. In addition to in vivo studies on topics such as gastrulation, embryonic patterning, cell polarity, and morphogenesis, recent studies using gastruloids and organoids, which recapitulate embryogenesis and organogenesis in in vitro cell culture, were also presented at this symposium, entitled Self-Organization in Biology. Most of the reported studies used vertebrate models such as mice, frogs, and zebrafish; however, evolutionary studies involving invertebrate and plant models were also presented. Presentations employing traditional methods such as cell transplantation and phenotype screening, and state-of-the-art technologies such as single-cell omics, high-resolution imaging, and computational analysis showed that experimental embryology has a long history, to which studies of the organizer have contributed significantly. Here we discuss memorable aspects of the symposium in the hope that this report will encourage young scientists to actively participate in face-to-face international conferences.", "classifications": [ { "id": "JPMJCR1923", "label": "JPMJCR1923", "researcher": "Satoshi Sawai", "type": "grant" }, { "id": "Sawai", "label": "Group Sawai", "parent": "Sawai", "type": "group" }, { "id": "Sawai", "label": "Team Sawai", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Satoshi", "last_name": "Kuwana", "name": null }, { "creator_type": "author", "first_name": "Yuuri", "last_name": "Yasuoka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/dgd.12954" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "39777708" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Developmental Biology", "descriptor_ui": "D015509", "major_topic": true }, { "descriptor": "Embryology", "descriptor_ui": "D004626", "major_topic": true }, { "descriptor": "Gastrula", "descriptor_ui": "D005775", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false } ], "publication": { "conference_name": null, "date": "2025 Jan 8", "date_precision": "day", "issue": "", "normalized_date": "2025-01-08", "pages": "", "proceedings_title": null, "publisher": "", "title": "Development, growth & differentiation", "volume": "", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Meeting report about self-organization in biology: Freiburg Spemann-Mangold Centennial Symposium.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: Chronic kidney disease (CKD) causes progressive and irreversible damage to the kidneys. Renal biopsies are essential for diagnosing the etiology and prognosis of CKD, while accurate quantification of tubulo-interstitial injuries from whole slide images (WSIs) of renal biopsy specimens is challenging with visual inspection alone. METHODS: We develop a deep learning-based method named DLRS to quantify interstitial fibrosis and inflammatory cell infiltration as tubulo-interstitial injury scores, from WSIs of renal biopsy specimens. DLRS segments WSIs into non-tissue areas, glomeruli, tubules, interstitium, and arteries, and detects interstitial nuclei. It then quantifies these tubulo-interstitial injury scores using the segmented tissues and detected nuclei. RESULTS: Applied to WSIs from 71 Japanese CKD patients with diabetic nephropathy or benign nephrosclerosis, DLRS-derived scores show concordance with nephrologists' evaluations. Notably, the DLRS-derived fibrosis score has a higher correlation with the estimated glomerular filtration rate (eGFR) at biopsy than scores from nephrologists' evaluations. Validated on WSIs from 28 Japanese tubulointerstitial nephritis patients and 49 European-ancestry patients with nephrosclerosis, DLRS-derived scores show a significant correlation with eGFR. In an expanded analysis of 238 Japanese CKD patients, including 167 from another hospital, deviations in eGFR from expected values based on DLRS-derived scores correlate with annual eGFR decline after biopsy. Inclusion of these deviations and DLRS-derived fibrosis scores improve predictions of the annual eGFR decline. CONCLUSIONS: DLRS-derived tubulo-interstitial injury scores are concordant with nephrologists' evaluations and correlated with eGFR across different populations and institutions. The effectiveness of DLRS-derived scores for predicting annual eGFR decline highlights the potential of DLRS as a predictor of renal prognosis.", "classifications": [ { "id": "Okamoto", "label": "Group Okamoto", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Nonoka", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Kaname", "last_name": "Kojima", "name": null }, { "creator_type": "author", "first_name": "Silvia", "last_name": "Malvica", "name": null }, { "creator_type": "author", "first_name": "Kenshi", "last_name": "Yamasaki", "name": null }, { "creator_type": "author", "first_name": "Yoichiro", "last_name": "Chikamatsu", "name": null }, { "creator_type": "author", "first_name": "Yuji", "last_name": "Oe", "name": null }, { "creator_type": "author", "first_name": "Tasuku", "last_name": "Nagasawa", "name": null }, { "creator_type": "author", "first_name": "Ekyu", "last_name": "Kondo", "name": null }, { "creator_type": "author", "first_name": "Satoru", "last_name": "Sanada", "name": null }, { "creator_type": "author", "first_name": "Setsuya", "last_name": "Aiba", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Mariko", "last_name": "Miyazaki", "name": null }, { "creator_type": "author", "first_name": "Sadayoshi", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Mitsuhiro", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Tetsuhiro", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Kengo", "last_name": "Kinoshita", "name": null }, { "creator_type": "author", "first_name": "Yoshihide", "last_name": "Asano", "name": null }, { "creator_type": "author", "first_name": "Avi Z.", "last_name": "Rosenberg", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Okamoto", "name": null }, { "creator_type": "author", "first_name": "Kosuke", "last_name": "Shido", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s43856-024-00708-3" }, "pmcid": { "normalized": "PMC11701080" }, "pmid": { "normalized": "39757253" } }, "mesh": [], "publication": { "conference_name": null, "date": "2025 Jan 5", "date_precision": "day", "issue": "1", "normalized_date": "2025-01-05", "pages": "3", "proceedings_title": null, "publisher": "", "title": "Communications medicine", "volume": "5", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Deep learning-based histopathological assessment of tubulo-interstitial injury in chronic kidney diseases.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The peri-operative management of non-small cell lung cancer (NSCLC) in earlier stage disease has seen significant advances in recent years with the incorporation of immune checkpoint inhibitors and targeted therapy. However, many unanswered questions and challenges remain, including the application of clinical trial data to routine clinical practice. Recognising the unique demographic profile of Asian patients with NSCLC and heterogeneous healthcare systems, the Asian Thoracic Oncology Research Group (ATORG) convened a consensus meeting in Singapore on 26 April 2024 to discuss relevant issues spanning diagnostic testing to post-neoadjuvant treatment considerations and future directions. An interdisciplinary group of 19 experts comprising medical oncologists, thoracic surgeons, radiation oncologists, pulmonologists and pathologists from Singapore, Hong Kong, Mainland China, Korea, Japan, Taiwan, India, Malaysia, Thailand, Vietnam and Australia met to discuss emerging data, identify existing gaps in clinical care and develop a multidisciplinary, multinational expert consensus statement on the peri-operative management of NSCLC tailored to the Asia-Pacific region.", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Stephanie P. L.", "last_name": "Saw", "name": null }, { "creator_type": "author", "first_name": "Wen-Zhao", "last_name": "Zhong", "name": null }, { "creator_type": "author", "first_name": "Rui", "last_name": "Fu", "name": null }, { "creator_type": "author", "first_name": "Molly S. C.", "last_name": "Li", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Goto", "name": null }, { "creator_type": "author", "first_name": "Stephen B.", "last_name": "Fox", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null }, { "creator_type": "author", "first_name": "Boon-Hean", "last_name": "Ong", "name": null }, { "creator_type": "author", "first_name": "Calvin S. H.", "last_name": "Ng", "name": null }, { "creator_type": "author", "first_name": "David D. W.", "last_name": "Lee", "name": null }, { "creator_type": "author", "first_name": "Pham", "last_name": "Cam Phuong", "name": null }, { "creator_type": "author", "first_name": "In Kyu", "last_name": "Park", "name": null }, { "creator_type": "author", "first_name": "James C. H.", "last_name": "Yang", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Tsuboi", "name": null }, { "creator_type": "author", "first_name": "Lye Mun", "last_name": "Tho", "name": null }, { "creator_type": "author", "first_name": "Thomas", "last_name": "John", "name": null }, { "creator_type": "author", "first_name": "Hsao-Hsun", "last_name": "Hsu", "name": null }, { "creator_type": "author", "first_name": "Daniel S. W.", "last_name": "Tan", "name": null }, { "creator_type": "author", "first_name": "Tony S. K.", "last_name": "Mok", "name": null }, { "creator_type": "author", "first_name": "Thanyanan", "last_name": "Reungwetwattana", "name": null }, { "creator_type": "author", "first_name": "Navneet", "last_name": "Singh", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.lungcan.2024.108076" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "39799810" } }, "mesh": [ { "descriptor": "Asia", "descriptor_ui": "D001208", "major_topic": false }, { "descriptor": "Carcinoma, Non-Small-Cell Lung", "descriptor_ui": "D002289", "major_topic": true }, { "descriptor": "Disease Management", "descriptor_ui": "D019468", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Lung Neoplasms", "descriptor_ui": "D008175", "major_topic": true }, { "descriptor": "Perioperative Care", "descriptor_ui": "D019990", "major_topic": true } ], "publication": { "conference_name": null, "date": "2025 Jan 2", "date_precision": "day", "issue": "", "normalized_date": "2025-01-02", "pages": "108076", "proceedings_title": null, "publisher": "", "title": "Lung cancer (Amsterdam, Netherlands)", "volume": "200", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Asian Thoracic Oncology Research Group expert consensus statement on the peri-operative management of non-small cell lung cancer.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Heterogeneity is a critical determinant for multicellular pattern formation. Although the importance of microscale and macroscale heterogeneity at the single-cell and whole-system levels, respectively, has been well accepted, the presence and functions of mesoscale heterogeneity, such as cell clusters with distinct properties, have been poorly recognized. We investigated the biological importance of mesoscale heterogeneity in signal-relaying abilities (excitability) in the self-organization of spiral waves of intercellular communications by studying the self-organized pattern formation in a population of Dictyostelium discoideum cells, a classical signal-relaying system model. By utilizing pulse-count analysis to evaluate cellular excitability, we successfully visualized the development of mesoscale heterogeneity in excitability, whose spatial scale was comparably large to that of the traveling waves of intercellular communication. Together with perturbation experiments, our detailed analysis of the structural change in mesoscale heterogeneity and associated wave dynamics demonstrated the functional importance of mesoscale heterogeneity in generating the spiral wave pattern, whose experimental observations were first realized. We propose that mesoscale heterogeneity, in addition to microscale and macroscale heterogeneities, is a critical determinant of diverse multicellular pattern formations.", "classifications": [ { "id": "Onami", "label": "Group Onami", "parent": "Fujiwara", "type": "group" }, { "id": "Fujiwara", "label": "Team Fujiwara", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Taishi", "last_name": "Kakizuka", "name": null }, { "creator_type": "author", "first_name": "Hidenori", "last_name": "Nakaoka", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Hara", "name": null }, { "creator_type": "author", "first_name": "Aya", "last_name": "Ichiraku", "name": null }, { "creator_type": "author", "first_name": "Yoshiyuki", "last_name": "Arai", "name": null }, { "creator_type": "author", "first_name": "Hiroya", "last_name": "Itoga", "name": null }, { "creator_type": "author", "first_name": "Shuichi", "last_name": "Onami", "name": null }, { "creator_type": "author", "first_name": "Taro", "last_name": "Ichimura", "name": null }, { "creator_type": "author", "first_name": "Takeharu", "last_name": "Nagai", "name": null }, { "creator_type": "author", "first_name": "Kazuki", "last_name": "Horikawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41598-025-85759-9" }, "pmcid": { "normalized": "PMC11717926" }, "pmid": { "normalized": "39789232" } }, "mesh": [ { "descriptor": "Cell Communication", "descriptor_ui": "D002450", "major_topic": false }, { "descriptor": "Dictyostelium", "descriptor_ui": "D004023", "major_topic": true }, { "descriptor": "Models, Biological", "descriptor_ui": "D008954", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false } ], "publication": { "conference_name": null, "date": "2025-01", "date_precision": "month", "issue": "1", "normalized_date": "2025-01", "pages": "1422", "proceedings_title": null, "publisher": "", "title": "Scientific Reports", "volume": "15", "year": 2025 }, "ssbd": { "database": [], "repository": [ "ssbd-repos-000173" ] }, "title": "Mesoscale heterogeneity is a critical determinant for spiral pattern formation in developing social amoeba", "url": "https://www.nature.com/articles/s41598-025-85759-9", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Subclinical Cushing's syndrome (SCS) is frequently encountered during the clinical evaluation of adrenal incidentalomas and is typically associated with reduced levels of serum dehydroepiandrosterone sulfate (DHEA-S). Cytochrome b5 is a component of the electron transfer system that enhances the activity of 17, 20-lyase relative to that of 17a-hydroxylase. Therefore, tumors harboring cytochrome b5 might be associated with dehydroepiandrosterone sulfotransferase (DHEA-ST) expression, resulting in unsuppressed serum DHEA-S levels. Here, we reported the first case of SCS with elevated serum DHEA-S levels in an incidentally detected adrenocortical adenoma showing immunohistochemical positivity for both cytochrome b5 and DHEA-ST.", "classifications": [ { "id": "Suzuki", "label": "Group Suzuki", "parent": "Takekawa", "type": "group" }, { "id": "Takekawa", "label": "Team Takekawa", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Ichiro", "last_name": "Abe", "name": null }, { "creator_type": "author", "first_name": "Yuto", "last_name": "Yamazaki", "name": null }, { "creator_type": "author", "first_name": "Ayuko", "last_name": "Higashi", "name": null }, { "creator_type": "author", "first_name": "Kentaro", "last_name": "Ochi", "name": null }, { "creator_type": "author", "first_name": "Keita", "last_name": "Kubo", "name": null }, { "creator_type": "author", "first_name": "Yuya", "last_name": "Fujita", "name": null }, { "creator_type": "author", "first_name": "Kaori", "last_name": "Takeshita", "name": null }, { "creator_type": "author", "first_name": "Toshiaki", "last_name": "Wada", "name": null }, { "creator_type": "author", "first_name": "Ryo", "last_name": "Mitsuoka", "name": null }, { "creator_type": "author", "first_name": "Yo", "last_name": "Yamashita", "name": null }, { "creator_type": "author", "first_name": "Ryoko", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Tamotsu", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Tadachika", "last_name": "Kudo", "name": null }, { "creator_type": "author", "first_name": "Shigero", "last_name": "Miyajima", "name": null }, { "creator_type": "author", "first_name": "Tatsu", "last_name": "Ishii", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Nimura", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Hironobu", "last_name": "Sasano", "name": null }, { "creator_type": "author", "first_name": "Kunihisa", "last_name": "Kobayashi", "name": null } ], "identifiers": { "doi": { "normalized": "10.3389/fendo.2025.1624396" }, "pmcid": { "normalized": "PMC12326150" }, "pmid": { "normalized": "40771281" } }, "mesh": [ { "descriptor": "Adrenal Cortex Neoplasms", "descriptor_ui": "D000306", "major_topic": true }, { "descriptor": "Adrenocortical Adenoma", "descriptor_ui": "D018246", "major_topic": true }, { "descriptor": "Cushing Syndrome", "descriptor_ui": "D003480", "major_topic": true }, { "descriptor": "Cytochromes b5", "descriptor_ui": "D015786", "major_topic": true }, { "descriptor": "Dehydroepiandrosterone Sulfate", "descriptor_ui": "D019314", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Sulfotransferases", "descriptor_ui": "D015238", "major_topic": true } ], "publication": { "conference_name": null, "date": "2025", "date_precision": "year", "issue": "", "normalized_date": "2025", "pages": "1624396", "proceedings_title": null, "publisher": "", "title": "Frontiers in endocrinology", "volume": "16", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Case Report: Adrenocortical adenoma harboring atypical subclinical Cushing's syndrome with dehydroepiandrosterone sulfate transferase and cytochrome b5 expression in tumor cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The presence of redox-active molecules containing catenated sulfur atoms (supersulfides) in living organisms has led to a review of the concepts of redox biology and its translational strategy. Glutathione (GSH) is the body’s primary detoxifier and antioxidant, and its oxidized form (GSSG) has been considered as a marker of oxidative status. However, we report that GSSG, but not reduced GSH, prevents ischemic supersulfide catabolism-associated heart failure in male mice by electrophilic modification of dynamin-related protein (Drp1). In healthy exercised hearts, the redox-sensitive Cys644 of Drp1 is highly S-glutathionylated. Nearly 40% of Cys644 is normally polysulfidated, which is a preferential target for GSSG-mediated S-glutathionylation. Cys644 S-glutathionylation is resistant to Drp1 depolysulfidation-dependent mitochondrial hyperfission and myocardial dysfunction caused by hypoxic stress. MD simulation of Drp1 structure and site-directed mutagenetic analysis reveal a functional interaction between Cys644 and a critical phosphorylation site Ser637, through Glu640. Bulky modification at Cys644 via polysulfidation or S-glutathionylation reduces Drp1 activity by disrupting Ser637-Glu640-Cys644 interaction. Disruption of Cys644 S-glutathionylation nullifies the cardioprotective effect of GSSG against heart failure after myocardial infarction. Our findings suggest a therapeutic potential of supersulfide-based Cys bulking on Drp1 for ischemic heart disease.", "classifications": [ { "id": "JPMJCR2024", "label": "JPMJCR2024", "researcher": "Motohiro Nishida", "type": "grant" }, { "id": "Akaike", "label": "Group Akaike", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Group Nishida", "parent": "Nishida", "type": "group" }, { "id": "Nishimura", "label": "Group Nishimura", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Akiyuki", "last_name": "Nishimura", "name": null }, { "creator_type": "author", "first_name": "Seiryo", "last_name": "Ogata", "name": null }, { "creator_type": "author", "first_name": "Xiaokang", "last_name": "Tang", "name": null }, { "creator_type": "author", "first_name": "Kowit", "last_name": "Hengphasatporn", "name": null }, { "creator_type": "author", "first_name": "Keitaro", "last_name": "Umezawa", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Sanbo", "name": null }, { "creator_type": "author", "first_name": "Masumi", "last_name": "Hirabayashi", "name": null }, { "creator_type": "author", "first_name": "Yuri", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Yuko", "last_name": "Ibuki", "name": null }, { "creator_type": "author", "first_name": "Yoshito", "last_name": "Kumagai", "name": null }, { "creator_type": "author", "first_name": "Kenta", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Yasunari", "last_name": "Kanda", "name": null }, { "creator_type": "author", "first_name": "Yasuteru", "last_name": "Urano", "name": null }, { "creator_type": "author", "first_name": "Yasuteru", "last_name": "Shigeta", "name": null }, { "creator_type": "author", "first_name": "Takaaki", "last_name": "Akaike", "name": null }, { "creator_type": "author", "first_name": "Motohiro", "last_name": "Nishida", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41467-024-55661-5" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "39747092" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cysteine", "descriptor_ui": "D003545", "major_topic": false }, { "descriptor": "Dynamins", "descriptor_ui": "D034281", "major_topic": true }, { "descriptor": "Glutathione", "descriptor_ui": "D005978", "major_topic": true }, { "descriptor": "Heart Failure", "descriptor_ui": "D006333", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Myocardial Ischemia", "descriptor_ui": "D017202", "major_topic": false }, { "descriptor": "Myocardium", "descriptor_ui": "D009206", "major_topic": false }, { "descriptor": "Oxidation-Reduction", "descriptor_ui": "D010084", "major_topic": false }, { "descriptor": "Oxidative Stress", "descriptor_ui": "D018384", "major_topic": false }, { "descriptor": "Phosphorylation", "descriptor_ui": "D010766", "major_topic": false }, { "descriptor": "Sulfides", "descriptor_ui": "D013440", "major_topic": true } ], "publication": { "conference_name": null, "date": "2025", "date_precision": "year", "issue": "", "normalized_date": "2025", "pages": "", "proceedings_title": null, "publisher": "", "title": "Nature Communications", "volume": "16", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Polysulfur-based bulking of dynamin-related protein 1 prevents ischemic sulfide catabolism and heart failure in mice.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Plants develop characteristic shoot architectures by extending branches at specific angles. Primary shoots bend in response to gravity and then adjust the orientation through an organ-straightening process to achieve a mechanically favorable shape. However, how plants integrate branch structure with the shoot architecture remains uncertain. Here, we examined the lateral branch morphology of Arabidopsis thaliana mutants for myosin XI motor proteins through a combination of three-dimensional reconstruction and temporal imaging. The wild type and myosin xif mutant formed S-shaped branches and gradually adjusted the branch angle upwards. The myosin xik mutant exhibited straighter and drooping branches and maintained branch angles. The myosin xif xik double mutant formed branches with irregular directional changes with fluctuating angles. These results suggest that MYOSIN XIk and XIf are required for the establishment of branch morphology through upward bending, stabilizing growth direction, and maintaining curvature.", "classifications": [ { "id": "Higaki", "label": "Group Higaki", "parent": "Ueda", "type": "group" }, { "id": "Ueda", "label": "Team Ueda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Daichi", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Itsuki", "last_name": "Kunita", "name": null }, { "creator_type": "author", "first_name": "Masashi", "last_name": "Toda", "name": null }, { "creator_type": "author", "first_name": "Haruko", "last_name": "Ueda", "name": null }, { "creator_type": "author", "first_name": "Takumi", "last_name": "Higaki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1017/qpb.2025.10007" }, "pmcid": { "normalized": "PMC12186554" }, "pmid": { "normalized": "40557251" } }, "mesh": [], "publication": { "conference_name": null, "date": "2025", "date_precision": "year", "issue": "", "normalized_date": "2025", "pages": "e15", "proceedings_title": null, "publisher": "", "title": "Quantitative plant biology", "volume": "6", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Four-dimensional phenotyping reveals MYOSIN XI-dependent establishment of branch morphology through upward- and stably-directed growth in Arabidopsis.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The hypothalamus is the gray matter of the ventral portion of the diencephalon. The hypothalamus is the higher center of the autonomic nervous system and is involved in the regulation of various homeostatic mechanisms. It also modulates respiration by facilitating the respiratory network. Among subregions of the hypothalamus, the paraventricular nucleus, lateral hypothalamic area, perifornical area, dorsomedial and posterior hypothalamus play particularly important roles in respiratory control. Neurons in these regions have extensive and complex interconnectivity with the cerebral cortex, pons, medulla, spinal cord, and other brain areas. These hypothalamic regions are involved in the maintenance of basal ventilation, respiratory responses to hypoxic and hypercapnic conditions, respiratory augmentation during dynamic exercise, and respiratory modulation in awake and sleep states. Disorders affecting the hypothalamus such as narcolepsy, ROHHAD syndrome, and Prader-Willi syndrome could lead to respiratory abnormalities. However, the role of the hypothalamus in respiratory control, especially its interplay with other local respiratory networks has not yet been fully elucidated. Further clarification of these issues would contribute to a better understanding of the hypothalamus-mediated respiratory control and the pathophysiology of respiratory disorders underlain by hypothalamic dysfunction, as well as to the development of new targeted therapies.", "classifications": [ { "id": "Yokota", "label": "Group Yokota", "parent": "Enomoto", "type": "group" }, { "id": "Enomoto", "label": "Team Enomoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Isato", "last_name": "Fukushi", "name": null }, { "creator_type": "author", "first_name": "Shigefumi", "last_name": "Yokota", "name": null }, { "creator_type": "author", "first_name": "Yohei", "last_name": "Hasebe", "name": null }, { "creator_type": "author", "first_name": "Mieczyslaw", "last_name": "Pokorski", "name": null }, { "creator_type": "author", "first_name": "Yasumasa", "last_name": "Okada", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/bs.vh.2024.06.006" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "39864940" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Hypothalamus", "descriptor_ui": "D007031", "major_topic": true }, { "descriptor": "Respiration", "descriptor_ui": "D012119", "major_topic": true } ], "publication": { "conference_name": null, "date": "2025", "date_precision": "year", "issue": "", "normalized_date": "2025", "pages": "125-152", "proceedings_title": null, "publisher": "", "title": "Vitamins and hormones", "volume": "127", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Modulation of respiration and hypothalamus.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Neural circuits are composed of numerous neurons that perform diverse functions. Understanding the mechanisms of neural processing requires elucidating the connections among individual neurons. Rabies virus (RV)-mediated trans-synaptic tracing enables the visualization of direct presynaptic neurons of a defined neural population, facilitating the precise mapping of neural circuits across various brain regions. This method relies on RV mutants that require the expression of the TVA receptor and rabies glycoprotein to infect and spread to presynaptic neurons. Traditionally, adeno-associated virus (AAV) has been used to express these proteins. However, because AAV requires several weeks to achieve sufficient gene expression, it is challenging to use this approach for studying neural connections during postnatal development. To address this limitation, we generated a transgenic mouse line, termed Ai162-nCTG, which expresses nuclear-localized mCherry, the TVA receptor, and rabies glycoprotein in a Cre-dependent manner. As a proof-of-principle, we crossed the Ai162-nCTG line with the vasopressin-Cre line. In the paraventricular hypothalamic nucleus, where a major cluster of vasopressin neurons exists, mCherry expression was highly specific to vasopressin neurons, although not all vasopressin neurons co-expressed mCherry. We injected RV into the paraventricular hypothalamic nucleus and compared the labeling patterns with those of the conventional AAV-based approach. Although both methods labeled input cells in similar brain regions, the AAV-based approach was superior in terms of labeling efficiency. We also demonstrated that the Ai162-nCTG-based method enables rabies virus-mediated trans-synaptic tracing in mice at postnatal day 7 and 30. The distribution of presynaptic neurons was largely similar in the juvenile and adult stages, suggesting that paraventricular vasopressin neurons do not significantly change their presynaptic inputs during post-weaning development. Taken together, these findings suggest that the Ai162-nCTG line can be used for rabies virus-mediated trans-synaptic tracing when AAV administration is challenging. We also acknowledge and discuss the technical constraints associated with this mouse line.", "classifications": [ { "id": "Miyamichi", "label": "Group Miyamichi", "parent": "Enomoto", "type": "group" }, { "id": "Enomoto", "label": "Team Enomoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Kengo", "last_name": "Inada", "name": null }, { "creator_type": "author", "first_name": "Mitsue", "last_name": "Hagihara", "name": null }, { "creator_type": "author", "first_name": "Miho", "last_name": "Kihara", "name": null }, { "creator_type": "author", "first_name": "Takaya", "last_name": "Abe", "name": null }, { "creator_type": "author", "first_name": "Kazunari", "last_name": "Miyamichi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1371/journal.pone.0323629" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "40354365" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Avian Proteins", "descriptor_ui": "D030161", "major_topic": false }, { "descriptor": "Brain", "descriptor_ui": "D001921", "major_topic": true }, { "descriptor": "Luminescent Proteins", "descriptor_ui": "D008164", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Transgenic", "descriptor_ui": "D008822", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Rabies virus", "descriptor_ui": "D011820", "major_topic": true }, { "descriptor": "Receptors, Virus", "descriptor_ui": "D011991", "major_topic": false }, { "descriptor": "Red Fluorescent Protein", "descriptor_ui": "D000097573", "major_topic": false }, { "descriptor": "Synapses", "descriptor_ui": "D013569", "major_topic": true } ], "publication": { "conference_name": null, "date": "2025", "date_precision": "year", "issue": "5", "normalized_date": "2025", "pages": "e0323629", "proceedings_title": null, "publisher": "", "title": "PloS one", "volume": "20", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "A transgenic mouse line for rabies virus-mediated trans-synaptic tracing in the postnatal developing brain.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "INTRODUCTION: Self-esteem (SE) can significantly affect individual well-being and has been linked to various psychiatric conditions. SE involves cognitive and emotional regulation within a social context. Prior research focusing on young adults has indicated neural correlations in prefrontal cortex areas but presented inconsistent findings. Our study expanded this to a broader age range and covariates, and examined the influence of subthreshold depression, emphasizing the functional role of the dorsolateral (dlPFC), ventrolateral prefrontal cortices (vlPFC) and cerebellum in social cognition and emotional regulation of social exclusion. METHODS: We conducted resting-state functional magnetic resonance imaging analyses on 114 participants to investigate the neural correlates of self-esteem. RESULTS: We found that high SE correlated with robust functional connectivity between the left dlPFC and posterior cerebellum. Associations between the left dlPFC and right lingual gyrus, the right vlPFC and insula were FDR-survived, along with diminished connectivity between the left vlPFC, angular gyri, and thalamus. DISCUSSION: These results not only support our hypothesis regarding the dual role of SE-which includes its social cognitive role in avoiding social exclusion and its emotional resilience in enduring such exclusion-but also suggest a potential link with rumination.", "classifications": [ { "id": "Fujiwara", "label": "Group Fujiwara", "parent": "Fujiwara", "type": "group" }, { "id": "Fujiwara", "label": "Team Fujiwara", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Morio", "last_name": "Aki", "name": null }, { "creator_type": "author", "first_name": "Mami", "last_name": "Shibata", "name": null }, { "creator_type": "author", "first_name": "Yoshihisa", "last_name": "Fujita", "name": null }, { "creator_type": "author", "first_name": "Michael", "last_name": "Spantios", "name": null }, { "creator_type": "author", "first_name": "Kei", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Tsukasa", "last_name": "Ueno", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Miyagi", "name": null }, { "creator_type": "author", "first_name": "Sayaka", "last_name": "Yoshimura", "name": null }, { "creator_type": "author", "first_name": "Naoya", "last_name": "Oishi", "name": null }, { "creator_type": "author", "first_name": "Toshiya", "last_name": "Murai", "name": null }, { "creator_type": "author", "first_name": "Hironobu", "last_name": "Fujiwara", "name": null } ], "identifiers": { "doi": { "normalized": "10.3389/fnins.2025.1588567" }, "pmcid": { "normalized": "PMC12130037" }, "pmid": { "normalized": "40463590" } }, "mesh": [], "publication": { "conference_name": null, "date": "2025", "date_precision": "year", "issue": "", "normalized_date": "2025", "pages": "1588567", "proceedings_title": null, "publisher": "", "title": "Frontiers in neuroscience", "volume": "19", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Neural basis of self-esteem: social cognitive and emotional regulation insights.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Inflammatory bowel disease (IBD) is characterized by chronic intestinal inflammation where CD4(+) T lymphocytes play an essential role. Accumulating evidence suggests that immune responses driven by CD4(+) T cells are critically regulated by various metabolic pathways including oxidative phosphorylation and glycolysis. Here we show that CARS2/CPERS-dependent supersulfide metabolism restrains CD4(+) T cell proliferation in a cell-intrinsic manner. Under steady state, Cars2 (+/-) mice exhibited spontaneous accumulation of effector/memory CD4(+) T cells in the colon with age. In lymphopenic conditions, Cars2 (+/-) CD4(+) T cells showed enhanced cell cycle entry with reduced expression of a cell cycle inhibitor Trp53 and triggered an exacerbated form of colitis, the response being rescued by treatment with a supersulfide donor glutathione trisulfide (GSSSG). Furthermore, re-analysis of publicly available gene datasets of human colonic CD4(+) T lymphocytes revealed that downregulation of CARS2 was associated with pathogenesis of IBD, and indeed, addition of GSSSG inhibited human CD4(+) T cell proliferation in vitro. Together these observations reveal that CARS2/CPERS-dependent supersulfide metabolism is essential for homeostasis of intestinal effector/memory CD4(+) T cells, and further suggest that dysregulation of the same metabolic pathway can lead to development of gut inflammation both in mice and humans.", "classifications": [ { "id": "JPMJCR2024", "label": "JPMJCR2024", "researcher": "Motohiro Nishida", "type": "grant" }, { "id": "Akaike", "label": "Group Akaike", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Group Nishida", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Shunichi", "last_name": "Tayama", "name": null }, { "creator_type": "author", "first_name": "Yuya", "last_name": "Kitamura", "name": null }, { "creator_type": "author", "first_name": "Kyoga", "last_name": "Hiraide", "name": null }, { "creator_type": "author", "first_name": "Hibiki", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Jing", "last_name": "Li", "name": null }, { "creator_type": "author", "first_name": "Ziying", "last_name": "Yang", "name": null }, { "creator_type": "author", "first_name": "Ryoji", "last_name": "Mitsuwaka", "name": null }, { "creator_type": "author", "first_name": "Akihisa", "last_name": "Kawajiri", "name": null }, { "creator_type": "author", "first_name": "Kosuke", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Feng", "last_name": "Gao", "name": null }, { "creator_type": "author", "first_name": "Taku", "last_name": "Nakai", "name": null }, { "creator_type": "author", "first_name": "Yuko", "last_name": "Okuyama", "name": null }, { "creator_type": "author", "first_name": "Tadahisa", "last_name": "Numakura", "name": null }, { "creator_type": "author", "first_name": "Mitsuhiro", "last_name": "Yamada", "name": null }, { "creator_type": "author", "first_name": "Tomoaki", "last_name": "Ida", "name": null }, { "creator_type": "author", "first_name": "Masanobu", "last_name": "Morita", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Kawabe", "name": null }, { "creator_type": "author", "first_name": "Takaaki", "last_name": "Akaike", "name": null }, { "creator_type": "author", "first_name": "Naoto", "last_name": "Ishii", "name": null } ], "identifiers": { "doi": { "normalized": "10.3389/fimmu.2025.1506580" }, "pmcid": { "normalized": "PMC12037617" }, "pmid": { "normalized": "40303402" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "CD4-Positive T-Lymphocytes", "descriptor_ui": "D015496", "major_topic": true }, { "descriptor": "Cell Proliferation", "descriptor_ui": "D049109", "major_topic": false }, { "descriptor": "Colitis", "descriptor_ui": "D003092", "major_topic": true }, { "descriptor": "Disease Models, Animal", "descriptor_ui": "D004195", "major_topic": false }, { "descriptor": "Glutathione", "descriptor_ui": "D005978", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Inflammation", "descriptor_ui": "D007249", "major_topic": false }, { "descriptor": "Inflammatory Bowel Diseases", "descriptor_ui": "D015212", "major_topic": true }, { "descriptor": "Lymphocyte Activation", "descriptor_ui": "D008213", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Sulfides", "descriptor_ui": "D013440", "major_topic": true } ], "publication": { "conference_name": null, "date": "2025", "date_precision": "year", "issue": "", "normalized_date": "2025", "pages": "1506580", "proceedings_title": null, "publisher": "", "title": "Frontiers in immunology", "volume": "16", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Supersulfide controls intestinal inflammation by suppressing CD4(+) T cell proliferation.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "During the early postnatal period, neurons in sensory circuits dynamically remodel their connectivity to acquire discrete receptive fields. Neuronal activity is thought to play a central role in circuit remodeling during this period: Neuronal activity stabilizes some synaptic connections while eliminating others. Synaptic competition plays a central role in the binary choice between stabilization and elimination. While activity-dependent \"punishment signals\" propagating from winner to loser synapses have been hypothesized to drive synapse elimination, their exact nature has remained elusive. In this review, I summarize recent studies in mouse mitral cells that explain how only one dendrite is stabilized while others are eliminated, based on early postnatal spontaneous activity in the olfactory bulb. I discuss how the hypothetical punishment signals act on loser but not winner dendrites to establish only one primary dendrite per mitral cell, the anatomical basis for the odorant receptor-specific parallel information processing in the olfactory bulb.", "classifications": [ { "id": "Imai", "label": "Group Imai", "parent": "Enomoto", "type": "group" }, { "id": "Enomoto", "label": "Team Enomoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Takeshi", "last_name": "Imai", "name": null } ], "identifiers": { "doi": { "normalized": "10.3389/fncir.2025.1541926" }, "pmcid": { "normalized": "PMC11873734" }, "pmid": { "normalized": "40034992" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Dendrites", "descriptor_ui": "D003712", "major_topic": true }, { "descriptor": "Neuronal Plasticity", "descriptor_ui": "D009473", "major_topic": true }, { "descriptor": "Olfactory Bulb", "descriptor_ui": "D009830", "major_topic": true }, { "descriptor": "Synapses", "descriptor_ui": "D013569", "major_topic": true } ], "publication": { "conference_name": null, "date": "2025", "date_precision": "year", "issue": "", "normalized_date": "2025", "pages": "1541926", "proceedings_title": null, "publisher": "", "title": "Frontiers in neural circuits", "volume": "19", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Activity-dependent synaptic competition and dendrite pruning in developing mitral cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Inflammation is one defense mechanism of the body that has multiple origins, ranging from physical agents to infectious agents including viruses and bacteria. The resolution of inflammation has emerged as a critical endogenous process that protects host tissues from prolonged or excessive inflammation, which can become chronic. Failure of the inflammation resolution is a key pathological mechanism that drives the progression of numerous inflammatory diseases. Owing to the various side effects of currently available drugs to control inflammation, novel therapeutic agents that can prevent or suppress inflammation are needed. Supersulfides are highly reactive and biologically potent molecules that function as antioxidants, redox regulators, and modulators of cell signaling. The catenation state of individual sulfur atoms endows supersulfides with unique biological activities. Great strides have recently been made in achieving a molecular understanding of these sulfur species, which participate in various physiological and pathological pathways. This review mainly focuses on the anti-inflammatory effects of supersulfides. The review starts with an overview of supersulfide biology and highlights the roles of supersulfides in both immune and inflammatory responses. The various donors used to generate supersulfides are assessed as research tools and potential therapeutic agents. Deeper understanding of the molecular and cellular bases of supersulfide-driven biology can help guide the development of innovative therapeutic strategies to prevent and treat diseases associated with various immune and inflammatory responses.", "classifications": [ { "id": "JPMJCR2024", "label": "JPMJCR2024", "researcher": "Motohiro Nishida", "type": "grant" }, { "id": "Akaike", "label": "Group Akaike", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Group Nishida", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Tianli", "last_name": "Zhang", "name": null }, { "creator_type": "author", "first_name": "Yuexuan", "last_name": "Pan", "name": null }, { "creator_type": "author", "first_name": "Tomohiro", "last_name": "Sawa", "name": null }, { "creator_type": "author", "first_name": "Takaaki", "last_name": "Akaike", "name": null }, { "creator_type": "author", "first_name": "Tetsuro", "last_name": "Matsunaga", "name": null } ], "identifiers": { "doi": { "normalized": "10.3389/fimmu.2025.1581385" }, "pmcid": { "normalized": "PMC12040673" }, "pmid": { "normalized": "40308575" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Anti-Inflammatory Agents", "descriptor_ui": "D000893", "major_topic": true }, { "descriptor": "Antioxidants", "descriptor_ui": "D000975", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Inflammation", "descriptor_ui": "D007249", "major_topic": true }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Sulfides", "descriptor_ui": "D013440", "major_topic": true } ], "publication": { "conference_name": null, "date": "2025", "date_precision": "year", "issue": "", "normalized_date": "2025", "pages": "1581385", "proceedings_title": null, "publisher": "", "title": "Frontiers in immunology", "volume": "16", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Supersulfide donors and their therapeutic targets in inflammatory diseases.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: Ongoing debates question the harm of internet use with the evolving technology, as many individuals transition from regular to problematic internet use (PIU). The habenula (Hb), located between the thalamus and the third ventricle, is implicated in various psychiatric disorders. In addition, personality features have been suggested to play a role in the pathophysiology of PIU. AIMS: This study aimed to investigate Hb volumetry in individuals with subclinical PIU and the mediating effect of personality traits on this relationship. METHODS: 110 healthy adults in this cross-sectional study underwent structural magnetic resonance imaging. Hb segmentation was performed using a deep learning technique. The Internet Addiction Test (IAT) and the NEO Five-Factor Inventory were used to assess the PIU level and personality, respectively. Partial Spearman's correlation analyses were performed to explore the relationships between Hb volumetry, IAT and NEO. Multiple regression analysis was applied to identify personality traits that predict IAT scores. The significant trait was then treated as a mediator between Hb volume and IAT correlation in mediation analysis with a bootstrap value of 5000. RESULTS: Relative Hb volume was negatively correlated with IAT scores (partial rho=-0.142, p=0.009). The IAT score was positively correlated with neuroticism (partial rho=0.430, p<0.001) and negatively correlated with extraversion, agreeableness and conscientiousness (partial rho=-0.213, p<0.001; partial rho=-0.279, p<0.001; and partial rho=-0.327, p<0.001). There was a significant indirect effect of Hb volume on this model (beta=-0.061, p=0.048, boot 95% confidence interval: -0.149 to -0.001). CONCLUSIONS: This study uncovered a crucial link between reduced Hb volume and heightened PIU. Our findings highlight neuroticism as a key risk factor for developing PIU. Moreover, neuroticism was shown to mediate the relationship between Hb volume and PIU tendency, offering valuable insight into the complexities of this interaction.", "classifications": [ { "id": "Fujiwara", "label": "Group Fujiwara", "parent": "Fujiwara", "type": "group" }, { "id": "Fujiwara", "label": "Team Fujiwara", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Halwa", "last_name": "Zakia", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Kyuragi", "name": null }, { "creator_type": "author", "first_name": "Qi", "last_name": "Dai", "name": null }, { "creator_type": "author", "first_name": "Naoya", "last_name": "Oishi", "name": null }, { "creator_type": "author", "first_name": "Yuzuki", "last_name": "Ishikawa", "name": null }, { "creator_type": "author", "first_name": "Lichang", "last_name": "Yao", "name": null }, { "creator_type": "author", "first_name": "Morio", "last_name": "Aki", "name": null }, { "creator_type": "author", "first_name": "Toshiya", "last_name": "Murai", "name": null }, { "creator_type": "author", "first_name": "Hironobu", "last_name": "Fujiwara", "name": null } ], "identifiers": { "doi": { "normalized": "10.1136/gpsych-2024-101694" }, "pmcid": { "normalized": "PMC11815417" }, "pmid": { "normalized": "39944777" } }, "mesh": [], "publication": { "conference_name": null, "date": "2025", "date_precision": "year", "issue": "1", "normalized_date": "2025", "pages": "e101694", "proceedings_title": null, "publisher": "", "title": "General psychiatry", "volume": "38", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Association between the subclinical level of problematic internet use and habenula volume: a look at mediation effect of neuroticism.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The coordination of various brain regions achieves both volitional and forced motor control, but the role of the primary motor cortex in proficient running motor control remains unclear. This study trained mice to run at high performance (>10,000 rotations per day or >2,700 rotations per hour) using a running wheel, and then assessed the effects of the removal of bilateral cortical areas including the primary motor cortex on volitional (self-initiated) and forced (externally driven) running locomotion. The control sham-operated group revealed a quick recovery of volitional running, reaching half of the maximum daily rotation in 3.9 +/- 2.6 days (n = 10). In contrast, the cortical injury group took a significantly longer period (7.0 +/- 3.3 days, n = 15, p < 0.05) to reach half of the maximum volitional daily rotation, but recovered to preoperative levels in about two weeks. Furthermore, even 3 days after surgery to remove cortical regions, the running time on a treadmill moving at 35.3 cm/s, which is difficult for naive mice to run on, was not significantly different from that in the sham-operated group. These results suggest that the intact primary motor cortex is not necessarily required to execute trained fast-running locomotion, but rather contributes to the spontaneity of running in mice.", "classifications": [ { "id": "JPMJCR1921", "label": "JPMJCR1921", "researcher": "Itaru Imayoshi", "type": "grant" }, { "id": "Imayoshi", "label": "Group Imayoshi", "parent": "Imayoshi", "type": "group" }, { "id": "Imayoshi", "label": "Team Imayoshi", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Ryusei", "last_name": "Abo", "name": null }, { "creator_type": "author", "first_name": "Mei", "last_name": "Ishikawa", "name": null }, { "creator_type": "author", "first_name": "Rio", "last_name": "Shinohara", "name": null }, { "creator_type": "author", "first_name": "Takayuki", "last_name": "Michikawa", "name": null }, { "creator_type": "author", "first_name": "Itaru", "last_name": "Imayoshi", "name": null } ], "identifiers": { "doi": { "normalized": "10.3389/fncir.2025.1630932" }, "pmcid": { "normalized": "PMC12391011" }, "pmid": { "normalized": "40896520" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Motor Cortex", "descriptor_ui": "D009044", "major_topic": true }, { "descriptor": "Running", "descriptor_ui": "D012420", "major_topic": true }, { "descriptor": "Volition", "descriptor_ui": "D014836", "major_topic": true } ], "publication": { "conference_name": null, "date": "2025", "date_precision": "year", "issue": "", "normalized_date": "2025", "pages": "1630932", "proceedings_title": null, "publisher": "", "title": "Frontiers in neural circuits", "volume": "19", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Volitional and forced running ability in mice lacking intact primary motor cortex.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "INTRODUCTION: Although a number of neuroimaging studies on problematic internet use (PIU) have been conducted, few studies on non-problematic internet use (non-PIU) are available; therefore, the influences of non-PIU on brain function are unclear. Resting-state functional connectivity (rsFC) could be an appropriate tool to investigate subclinical samples, such as non-PIU, to capture the potentially subtle changes compared to clinical samples. In the context of rsFC, the default mode network (DMN), the central executive network (CEN), and the salience network (SN) are representative of the brain networks. Because accumulating studies have investigated rsFC between these networks in PIU samples, investigating rsFC between these networks in non-PIU samples could give us a clue to elucidate the neural basis of non-PIU in relation to those of PIU. METHODS: We recruited 119 healthy volunteers and used the General Problematic Internet Use Scale-2 (GPIUS-2) to measure their propensity to use the Internet. The GPIUS-2 consists of four subscales. We analyzed the correlation between the degree of Internet use assessed by the GPIUS-2 and the rsFC of the regions comprising DMN, CEN, and SN using resting-state functional magnetic resonance imaging in non-PIU samples. RESULTS: There was a positive correlation between the mood regulation subscale score and SN (bilateral anterior insula) - CEN (left lateral prefrontal cortex: LPFC), SN (left anterior insula) - DMN (medial prefrontal cortex: MPFC), and DMN (MPFC) - CEN (right LPFC) rsFC. Additionally, there was a negative correlation between the mood regulation subscale score and DMN - FPN rsFC. DISCUSSION: The correlations between rsFC and non-PIU suggest that non-PIU and PIU could influence rsFC in opposite directions. Furthermore, the hub regions comprising connections correlated with non-PIU in this study are involved in cognitive and emotional processes. One possible interpretation would be that the bilateral insula and synchronized LPFC activity in individuals with non-PIU results in well-functioning emotion regulation as an appropriate coping strategy, in contrast to PIU. These findings suggest that non-PIU might contribute to health promotion through mood regulation with alterations in the functional connectivity between the regions involved in mood regulation.", "classifications": [ { "id": "Fujiwara", "label": "Group Fujiwara", "parent": "Fujiwara", "type": "group" }, { "id": "Fujiwara", "label": "Team Fujiwara", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Mami", "last_name": "Shibata", "name": null }, { "creator_type": "author", "first_name": "Kosuke", "last_name": "Tsurumi", "name": null }, { "creator_type": "author", "first_name": "Kei", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Sayaka", "last_name": "Yoshimura", "name": null }, { "creator_type": "author", "first_name": "Michael", "last_name": "Spantios", "name": null }, { "creator_type": "author", "first_name": "Naoya", "last_name": "Oishi", "name": null }, { "creator_type": "author", "first_name": "Toshiya", "last_name": "Murai", "name": null }, { "creator_type": "author", "first_name": "Hironobu", "last_name": "Fujiwara", "name": null } ], "identifiers": { "doi": { "normalized": "10.3389/fnins.2025.1599987" }, "pmcid": { "normalized": "PMC12259676" }, "pmid": { "normalized": "40666258" } }, "mesh": [], "publication": { "conference_name": null, "date": "2025", "date_precision": "year", "issue": "", "normalized_date": "2025", "pages": "1599987", "proceedings_title": null, "publisher": "", "title": "Frontiers in neuroscience", "volume": "19", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Alterations of the default mode network, salience network, and frontoparietal network in non-problematic Internet use and their association with mood regulation: from an internet literacy perspective.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Because of its good spectral separation from green (GFP) and red (RFP) fluorescent proteins, blue fluorescent protein (BFP) is essential for multicolor live cell imaging. However, the commonly used bright mTagBFP2 strongly perturbs the cellular localization of Lifeact, an F-actin marker. As an alternative, we tested the expression of Electra2 in Dictyostelium . Both standalone and as a fusion tag to Lifeact, HistoneH1, or the Akt/PKB PH domain, Electra2 showed brightness comparable to that of mTagBFP2, with intracellular localization patterns consistent with those of GFP and RFP. Electra2 is a promising BFP of choice for studying actin and other targets.", "classifications": [ { "id": "JPMJCR1923", "label": "JPMJCR1923", "researcher": "Satoshi Sawai", "type": "grant" }, { "id": "Sawai", "label": "Group Sawai", "parent": "Sawai", "type": "group" }, { "id": "Sawai", "label": "Team Sawai", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Hidenori", "last_name": "Hashimura", "name": null }, { "creator_type": "author", "first_name": "Hibiki", "last_name": "Nakagawa", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Sawai", "name": null } ], "identifiers": { "doi": { "normalized": "10.17912/micropub.biology.001774" }, "pmcid": { "normalized": "PMC12413638" }, "pmid": { "normalized": "40918425" } }, "mesh": [], "publication": { "conference_name": null, "date": "2025", "date_precision": "year", "issue": "", "normalized_date": "2025", "pages": "", "proceedings_title": null, "publisher": "", "title": "microPublication biology", "volume": "2025", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Use of blue fluorescent protein Electra2 for live-cell imaging in Dictyostelium discoideum.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Currently, a variety of anticancer agents are used in the treatment of cancer. Since anticancer agents are used continuously over a long time, they carry the risk of side effects. One of the major side effects is cardiac dysfunction. For example, doxorubicin, an anthracycline-type anticancer agent, is clinically restricted because of its dose-dependent cardiotoxicity. Cardiotoxicity includes decreased ejection fraction, arrhythmias, and congestive heart failure, all of which are associated with high mortality rates. Therefore, it is important to assess the risk of cardiotoxicity of anticancer agents in advance. Cardiomyocytes require energy to beat and retain an abundance of mitochondria. We established quantitative measurements of mitochondrial length and respiratory activities using cardiomyocytes. We found that exposure of human iPS cell-derived cardiomyocytes (hiPSC-CMs) to anticancer agents with reported cardiotoxicity enhanced mitochondrial hyperfission and the oxygen consumption rate was significantly reduced. Knockdown of dynamin-related protein 1 (Drp1), mitochondrial fission-accelerating GTP-binding protein, suppressed mitochondrial hyperfission in hiPSC-CMs. This indicates that visualizing mitochondrial functions in hiPSC-CMs will be helpful in assessing the risk of cardiotoxicity caused by anticancer agents and that maintaining mitochondrial quality will become a new strategy to reduce anticancer agents-induced cardiotoxicity. In this review, we present the evaluation of cardiotoxicity targeting mitochondrial quality in anticancer agents, using osimertinib, a non-small cell lung cancer drug, as an example.", "classifications": [ { "id": "Nishida", "label": "Group Nishida", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yuri", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Yuya", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Moe", "last_name": "Kondo", "name": null }, { "creator_type": "author", "first_name": "Yasunari", "last_name": "Kanda", "name": null }, { "creator_type": "author", "first_name": "Motohiro", "last_name": "Nishida", "name": null } ], "identifiers": { "doi": { "normalized": "10.1254/fpj.24056" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "39756913" } }, "mesh": [ { "descriptor": "Antineoplastic Agents", "descriptor_ui": "D000970", "major_topic": true }, { "descriptor": "Cardiotoxicity", "descriptor_ui": "D066126", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Induced Pluripotent Stem Cells", "descriptor_ui": "D057026", "major_topic": true }, { "descriptor": "Mitochondria", "descriptor_ui": "D008928", "major_topic": true }, { "descriptor": "Mitochondria, Heart", "descriptor_ui": "D008929", "major_topic": false }, { "descriptor": "Myocytes, Cardiac", "descriptor_ui": "D032383", "major_topic": true }, { "descriptor": "Risk Assessment", "descriptor_ui": "D018570", "major_topic": false } ], "publication": { "conference_name": null, "date": "2025", "date_precision": "year", "issue": "1", "normalized_date": "2025", "pages": "9-12", "proceedings_title": null, "publisher": "", "title": "Nihon yakurigaku zasshi. Folia pharmacologica Japonica", "volume": "160", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "[Cardiotoxicity risk assessment of anticancer drugs by focusing on mitochondrial quality of human iPS cell-derived cardiomyocytes].", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Hi-C methods reveal 3D genome features but lack correspondence to dynamic chromatin behavior. PHi-C2, Python software, addresses this gap by transforming Hi-C data into polymer models. After the optimization algorithm, it enables us to calculate 3D conformations and conduct dynamic simulations, providing insights into chromatin dynamics, including the mean-squared displacement and rheological properties. This chapter introduces PHi-C2 usage, offering a tutorial for comprehensive 4D genome analysis.", "classifications": [ { "id": "Onami", "label": "Group Onami", "parent": "Fujiwara", "type": "group" }, { "id": "Fujiwara", "label": "Team Fujiwara", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Soya", "last_name": "Shinkai", "name": null }, { "creator_type": "author", "first_name": "Shuichi", "last_name": "Onami", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/978-1-0716-4136-1_16" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "39283458" } }, "mesh": [ { "descriptor": "Algorithms", "descriptor_ui": "D000465", "major_topic": true }, { "descriptor": "Chromatin", "descriptor_ui": "D002843", "major_topic": true }, { "descriptor": "Computational Biology", "descriptor_ui": "D019295", "major_topic": false }, { "descriptor": "Genome", "descriptor_ui": "D016678", "major_topic": false }, { "descriptor": "Genomics", "descriptor_ui": "D023281", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Software", "descriptor_ui": "D012984", "major_topic": true } ], "publication": { "conference_name": null, "date": "2025", "date_precision": "year", "issue": "", "normalized_date": "2025", "pages": "271-279", "proceedings_title": null, "publisher": "", "title": "Methods in molecular biology (Clifton, N.J.)", "volume": "2856", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "4D Genome Analysis Using PHi-C2.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "We investigate the behavior of self-propelled particles under cyclic stretching, inspired by the characteristic pattern dynamics observed in microtubule (MT) motility assays subjected to uniaxial cyclic substrate stretching. We develop a self-propelled particle model that incorporates the elastic energy acting on the filaments due to substrate deformation, successfully reproducing the experimentally observed MT patterns. Additionally, the general framework of the model enables systematic exploration of collective responses to various substrate deformations, offering potential applications in the manipulation of MT patterns and other active matter systems.", "classifications": [ { "id": "Ishihara", "label": "Group Ishihara", "parent": "Sawai", "type": "group" }, { "id": "Sawai", "label": "Team Sawai", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Takumi", "last_name": "Tagaki", "name": null }, { "creator_type": "author", "first_name": "Seiya", "last_name": "Nishikawa", "name": null }, { "creator_type": "author", "first_name": "Shuji", "last_name": "Ishihara", "name": null } ], "identifiers": { "doi": { "normalized": "10.1103/qysz-9fk3" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "41116414" } }, "mesh": [], "publication": { "conference_name": null, "date": "2025 Sep", "date_precision": "unknown", "issue": "3-1", "normalized_date": null, "pages": "034405", "proceedings_title": null, "publisher": "", "title": "Physical review. E", "volume": "112", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Active matter under cyclic stretch: Modeling microtubule alignment and bundling.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The unique architecture of the liver consists of hepatic lobules, dividing the hepatic features of metabolism into 2 distinct zones, namely the pericentral and periportal zones, the spatial characteristics of which are broadly defined as metabolic zonation. R-spondin3 (Rspo3), a bioactive protein promoting the Wnt signaling pathway, regulates metabolic features especially around hepatic central veins. However, the functional impact of hepatic metabolic zonation, regulated by the Rspo3/Wnt signaling pathway, on whole-body metabolism homeostasis remains poorly understood. In this study, we analyze the local functions of Rspo3 in the liver and the remote actions of hepatic Rspo3 on other organs of the body by using murine models. Rspo3 expression analysis shows that Rspo3 expression patterns are spatiotemporally controlled in the murine liver such that it locates in the pericentral zones and converges after feeding, and the dynamics of these processes are disturbed in obesity. We find that viral-mediated induction of Rspo3 in hepatic tissue of obesity improves insulin resistance and prevents body weight gain by restoring attenuated organ insulin sensitivities, reducing adipose tissue enlargement and reversing overstimulated adaptive thermogenesis. Denervation of the hepatic vagus suppresses these remote effects, derived from hepatic Rspo3 induction, toward adipose tissues and skeletal muscle, suggesting that signals are transduced via the neuronal communication consisting of afferent vagal and efferent sympathetic nerves. Furthermore, the non-neuronal inter-organ communication up-regulating muscle lipid utilization is partially responsible for the ameliorations of both fatty liver development and reduced skeletal muscle quality in obesity. In contrast, hepatic Rspo3 suppression through Cre-LoxP-mediated recombination system exacerbates diabetes due to glucose intolerance and insulin resistance, promotes fatty liver development and decreases skeletal muscle quality, resulting in obesity. Taken together, our study results reveal that modulation of hepatic Rspo3 contributes to maintaining systemic glucose metabolism and body composition via a newly identified inter-organ communication mechanism.", "classifications": [ { "id": "Suzuki", "label": "Group Suzuki", "parent": "Takekawa", "type": "group" }, { "id": "Takekawa", "label": "Team Takekawa", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Kenji", "last_name": "Uno", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Uchino", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Yohei", "last_name": "Sayama", "name": null }, { "creator_type": "author", "first_name": "Naoki", "last_name": "Edo", "name": null }, { "creator_type": "author", "first_name": "Kiyoko", "last_name": "Uno-Eder", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Morita", "name": null }, { "creator_type": "author", "first_name": "Toshio", "last_name": "Ishikawa", "name": null }, { "creator_type": "author", "first_name": "Miho", "last_name": "Koizumi", "name": null }, { "creator_type": "author", "first_name": "Hiroaki", "last_name": "Honda", "name": null }, { "creator_type": "author", "first_name": "Hideki", "last_name": "Katagiri", "name": null }, { "creator_type": "author", "first_name": "Kazuhisa", "last_name": "Tsukamoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1371/journal.pbio.3002955" }, "pmcid": { "normalized": "PMC11759367" }, "pmid": { "normalized": "39854351" } }, "mesh": [ { "descriptor": "Adipose Tissue", "descriptor_ui": "D000273", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Body Weight", "descriptor_ui": "D001835", "major_topic": false }, { "descriptor": "Glucose", "descriptor_ui": "D005947", "major_topic": true }, { "descriptor": "Insulin Resistance", "descriptor_ui": "D007333", "major_topic": false }, { "descriptor": "Liver", "descriptor_ui": "D008099", "major_topic": true }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Obesity", "descriptor_ui": "D009765", "major_topic": false }, { "descriptor": "Thermogenesis", "descriptor_ui": "D022722", "major_topic": false }, { "descriptor": "Thrombospondins", "descriptor_ui": "D019699", "major_topic": true }, { "descriptor": "Wnt Signaling Pathway", "descriptor_ui": "D060449", "major_topic": false } ], "publication": { "conference_name": null, "date": "2025 Jan", "date_precision": "unknown", "issue": "1", "normalized_date": null, "pages": "e3002955", "proceedings_title": null, "publisher": "", "title": "PLoS biology", "volume": "23", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Rspo3-mediated metabolic liver zonation regulates systemic glucose metabolism and body mass in mice.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Respiratory syncytial virus (RSV) is a seasonal respiratory pathogen that primarily affects young children, potentially causing severe lower respiratory tract disease. Despite the high disease burden, understanding of RSV pathophysiology remains limited. To address this, advanced RSV infection models are needed. Whereas HEp-2 cells are widely used because of their high susceptibility to RSV, they do not accurately reflect the host response of the human respiratory tract. In this study, we evaluated human-induced pluripotent stem cell-derived respiratory organoids, which contain respiratory epithelial cells, immune cells, fibroblasts, and vascular endothelial cells, for their potential to model RSV infection and support pharmaceutical research. RSV-infected organoids exhibited high viral genome and protein expression, epithelial layer destruction, and increased collagen accumulation. Pro-inflammatory cytokine levels in culture supernatants also increased post-infection. Furthermore, RSV infection was significantly inhibited by monoclonal antibodies (nirsevimab, palivizumab, suptavumab, or clesrovimab), although ribavirin showed limited efficacy. These findings highlight the utility of respiratory organoids for RSV research.", "classifications": [ { "id": "Yamamoto", "label": "Group Yamamoto", "parent": "Toyoshima", "type": "group" }, { "id": "Toyoshima", "label": "Team Toyoshima", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Rina", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Yukio", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Abeer", "last_name": "Keshta", "name": null }, { "creator_type": "author", "first_name": "Masaya", "last_name": "Sugiyama", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Kitai", "name": null }, { "creator_type": "author", "first_name": "Ai", "last_name": "Hirabayashi", "name": null }, { "creator_type": "author", "first_name": "Naoko", "last_name": "Yasuhara", "name": null }, { "creator_type": "author", "first_name": "Shiho", "last_name": "Morimoto", "name": null }, { "creator_type": "author", "first_name": "Ayaka", "last_name": "Sakamoto", "name": null }, { "creator_type": "author", "first_name": "Yasufumi", "last_name": "Matsumura", "name": null }, { "creator_type": "author", "first_name": "Hidekazu", "last_name": "Nishimura", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Noda", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Miki", "last_name": "Nagao", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Takeda", "name": null }, { "creator_type": "author", "first_name": "Kazuo", "last_name": "Takayama", "name": null } ], "identifiers": { "doi": { "normalized": "10.26508/lsa.202402837" }, "pmcid": { "normalized": "PMC12015132" }, "pmid": { "normalized": "40262853" } }, "mesh": [ { "descriptor": "Antibodies, Monoclonal", "descriptor_ui": "D000911", "major_topic": false }, { "descriptor": "Antiviral Agents", "descriptor_ui": "D000998", "major_topic": false }, { "descriptor": "Cytokines", "descriptor_ui": "D016207", "major_topic": false }, { "descriptor": "Epithelial Cells", "descriptor_ui": "D004847", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Induced Pluripotent Stem Cells", "descriptor_ui": "D057026", "major_topic": true }, { "descriptor": "Organoids", "descriptor_ui": "D009940", "major_topic": true }, { "descriptor": "Respiratory Syncytial Virus Infections", "descriptor_ui": "D018357", "major_topic": true }, { "descriptor": "Respiratory Syncytial Virus, Human", "descriptor_ui": "D018113", "major_topic": true }, { "descriptor": "Respiratory Syncytial Viruses", "descriptor_ui": "D012136", "major_topic": false } ], "publication": { "conference_name": null, "date": "2025 Jul", "date_precision": "unknown", "issue": "7", "normalized_date": null, "pages": "", "proceedings_title": null, "publisher": "", "title": "Life science alliance", "volume": "8", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Human iPS cell-derived respiratory organoids as a model for respiratory syncytial virus infection.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The mammalian target of rapamycin complex 1 (mTORC1) signaling pathway, composed of amino acid (AA)-sensing (Ragulator/LAMTOR-Rag) and growth factor (GF)-sensing (AKT-TSC1/2-Rheb) axes, pivotally regulates intracellular anabolism and catabolism. mTORC1 deregulation is associated with various metabolic diseases, including cancer and diabetes. As a key regulator of nutrient signaling, mTORC1 integrates a variety of nutrient signals. However, signal integration and crosstalk in the mTORC1 pathway remain incompletely understood. Therefore, in this study, we aimed to understand the complex mTORC1 signaling cascade by constructing an integrated mathematical model of temporal mTORC1 regulation using two AA-sensing and GF-sensing axes. Mathematical simulations and experimental data revealed robust AKT phosphorylation (P-T308/P-S473) after insulin stimulation, regardless of the intracellular AA levels. Conversely, AKT-mediated inhibitory TSC2 phosphorylation (P-T1462) substantially diminished during AA deprivation compared with AA treatment. Furthermore, we highlighted PP2A-mediated TSC2 dephosphorylation during AA removal, ensuring complete mTORC1 activation only upon concurrent AA and GF sensing. Thus, we elucidated mTORC1 signaling dynamics, revealing the complex interplay between AAs and GFs and offering insights into metabolic regulation.", "classifications": [ { "id": "JPMJCR2022", "label": "JPMJCR2022", "researcher": "Mutsuhiro Takekawa", "type": "grant" }, { "id": "Suzuki", "label": "Group Suzuki", "parent": "Takekawa", "type": "group" }, { "id": "Takekawa", "label": "Group Takekawa", "parent": "Takekawa", "type": "group" }, { "id": "Takekawa", "label": "Team Takekawa", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Takanori", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Shigeyuki", "last_name": "Nada", "name": null }, { "creator_type": "author", "first_name": "Masaki", "last_name": "Matsumoto", "name": null }, { "creator_type": "author", "first_name": "Nuha", "last_name": "Loling Othman", "name": null }, { "creator_type": "author", "first_name": "Hidetaka", "last_name": "Kosako", "name": null }, { "creator_type": "author", "first_name": "Kazuki", "last_name": "Ikeda", "name": null }, { "creator_type": "author", "first_name": "Naohiko", "last_name": "Koshikawa", "name": null }, { "creator_type": "author", "first_name": "Junya", "last_name": "Masumoto", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Sawasaki", "name": null }, { "creator_type": "author", "first_name": "Mutsuhiro", "last_name": "Takekawa", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Masato", "last_name": "Okada", "name": null } ], "identifiers": { "doi": { "normalized": "10.26508/lsa.202503206" }, "pmcid": { "normalized": "PMC12405003" }, "pmid": { "normalized": "40897470" } }, "mesh": [ { "descriptor": "Amino Acids", "descriptor_ui": "D000596", "major_topic": true }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Insulin", "descriptor_ui": "D007328", "major_topic": false }, { "descriptor": "Lysosomes", "descriptor_ui": "D008247", "major_topic": true }, { "descriptor": "Mechanistic Target of Rapamycin Complex 1", "descriptor_ui": "D000076222", "major_topic": true }, { "descriptor": "Phosphorylation", "descriptor_ui": "D010766", "major_topic": false }, { "descriptor": "Protein Phosphatase 2", "descriptor_ui": "D054648", "major_topic": true }, { "descriptor": "Proto-Oncogene Proteins c-akt", "descriptor_ui": "D051057", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Tuberous Sclerosis Complex 2 Protein", "descriptor_ui": "D000077005", "major_topic": true } ], "publication": { "conference_name": null, "date": "2025 Nov", "date_precision": "unknown", "issue": "11", "normalized_date": null, "pages": "", "proceedings_title": null, "publisher": "", "title": "Life science alliance", "volume": "8", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Amino acid-dependent TSC2 dephosphorylation by lysosome-PP2A regulates mTORC1 signaling transduction.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Chemical reaction network (CRN) theory is widely utilized to model and analyze a wide range of biochemical phenomena. Structural transformations and reductions serve as essential tools to better understand how topological properties of a CRN are related with specific functions. In this context, graph-based representations of CRNs have been explored; however, their connections to concentration dynamics and thermodynamics remain elusive. In this study, we propose a natural transformation from the classical complex-reaction graph to a species-transition graph, leveraging the conservation laws of the stoichiometric matrix. By introducing transition matrices on the species graph, the concentration dynamics of CRNs are reinterpreted as the differences between the physically observable inflow and outflow of species. This approach enables the formal lumping of multiple reactions into fewer interactions, which we demonstrate using a realistic metabolic model of E. coli. Additionally, we define species-specific thermodynamic quantities on the species graphs and establish bounds relating them to conventional reactionwise quantities. The specieswise bounds of conventional driving forces and entropy production rates can outperform the bounds determined by reactionwise flux fluctuations, as illustrated through numerical simulations with the Brusselator model. The proposed framework unifies graph-based representations of CRNs with concentration dynamics and thermodynamic principles, offering novel insights and computational advantages for analyzing complex biochemical networks.", "classifications": [ { "id": "Kobayashi", "label": "Group Kobayashi", "parent": "Wakamoto", "type": "group" }, { "id": "Wakamoto", "label": "Team Wakamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Keisuke", "last_name": "Sugie", "name": null }, { "creator_type": "author", "first_name": "Dimitri", "last_name": "Loutchko", "name": null }, { "creator_type": "author", "first_name": "Tetsuya J.", "last_name": "Kobayashi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1103/p42m-8bqy" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "41250401" } }, "mesh": [], "publication": { "conference_name": null, "date": "2025 Oct", "date_precision": "unknown", "issue": "4-1", "normalized_date": null, "pages": "044112", "proceedings_title": null, "publisher": "", "title": "Physical review. E", "volume": "112", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Transitions and thermodynamics on species graphs of chemical reaction networks.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: Esophageal squamous cell carcinoma (ESCC) represents an aggressive cancer type associated with poor prognosis, often treated with neoadjuvant chemotherapy (NAC) using cisplatin-based regimens. However, cisplatin resistance limits therapeutic efficacy, necessitating a deeper understanding of resistance mechanisms. L-type amino acid transporter 1 (LAT1) plays a crucial role in amino acid uptake and is linked to cancer cell survival through activation of the mammalian target of rapamycin (mTOR) pathway. The involvement of LAT1 in cisplatin resistance in ESCC remains unclear. METHODS: LAT1 expression in ESCC patient samples post-NAC was evaluated by immunohistochemistry, and its association with clinicopathological factors and survival outcomes was analyzed. ESCC cell lines with varying cisplatin sensitivities were assessed for LAT1 expression using western blotting. Amino acid metabolism was examined via radiotracer uptake of (18)F-FET and (18)F-FDG. RNA sequencing was conducted to identify differentially expressed genes associated with mTOR signaling and autophagy. Finally, the effect of the LAT1 inhibitor JPH203 on cell proliferation was tested. RESULTS: High LAT1 expression was significantly associated with larger tumor size, lymph node metastasis, advanced pathological stage, and poor NAC response. Patients with high LAT1 expression exhibited shorter disease-free survival and overall survival. Cisplatin-resistant ESCC cells (KYSE520) showed elevated LAT1 expression, which further increased following cisplatin treatment. Radiotracer assays revealed that (18)F-FET uptake was significantly higher in KYSE520 after cisplatin treatment compared to the sensitive cell line TE5. RNA sequencing identified regulation of mTOR pathway components and autophagy-related genes in cisplatin-resistant cells. Treatment with JPH203 significantly suppressed cell proliferation, particularly in KYSE520 cells, indicating LAT1's role in sustaining tumor cell survival under chemotherapy stress. CONCLUSION: LAT1 contributes to cisplatin resistance in ESCC by sustaining amino acid metabolism and promoting mTOR-dependent autophagy. Targeting LAT1 with JPH203 enhances cisplatin sensitivity, suggesting that LAT1 inhibition could be a promising therapeutic strategy for overcoming chemoresistance in ESCC.", "classifications": [ { "id": "Suzuki", "label": "Group Suzuki", "parent": "Takekawa", "type": "group" }, { "id": "Takekawa", "label": "Team Takekawa", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Takeru", "last_name": "Mozumi", "name": null }, { "creator_type": "author", "first_name": "Narumi", "last_name": "Harada-Shoji", "name": null }, { "creator_type": "author", "first_name": "Yohei", "last_name": "Ozawa", "name": null }, { "creator_type": "author", "first_name": "Yuto", "last_name": "Yamazaki", "name": null }, { "creator_type": "author", "first_name": "Ryoyu", "last_name": "Niikuni", "name": null }, { "creator_type": "author", "first_name": "Kentaro", "last_name": "Imai", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Taniyama", "name": null }, { "creator_type": "author", "first_name": "Chiaki", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Okamoto", "name": null }, { "creator_type": "author", "first_name": "Hirotaka", "last_name": "Ishida", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Kunimitsu", "name": null }, { "creator_type": "author", "first_name": "Iku", "last_name": "Sasaki-Higashimoto", "name": null }, { "creator_type": "author", "first_name": "Chisa", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Shozo", "last_name": "Furumoto", "name": null }, { "creator_type": "author", "first_name": "Takaaki", "last_name": "Abe", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Kamei", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/cam4.71234" }, "pmcid": { "normalized": "PMC12418084" }, "pmid": { "normalized": "40923294" } }, "mesh": [ { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Antineoplastic Agents", "descriptor_ui": "D000970", "major_topic": true }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Cell Proliferation", "descriptor_ui": "D049109", "major_topic": false }, { "descriptor": "Cisplatin", "descriptor_ui": "D002945", "major_topic": true }, { "descriptor": "Drug Resistance, Neoplasm", "descriptor_ui": "D019008", "major_topic": true }, { "descriptor": "Esophageal Neoplasms", "descriptor_ui": "D004938", "major_topic": true }, { "descriptor": "Esophageal Squamous Cell Carcinoma", "descriptor_ui": "D000077277", "major_topic": true }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Gene Expression Regulation, Neoplastic", "descriptor_ui": "D015972", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Large Neutral Amino Acid-Transporter 1", "descriptor_ui": "D027283", "major_topic": true }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "TOR Serine-Threonine Kinases", "descriptor_ui": "D058570", "major_topic": false } ], "publication": { "conference_name": null, "date": "2025 Sep", "date_precision": "unknown", "issue": "17", "normalized_date": null, "pages": "e71234", "proceedings_title": null, "publisher": "", "title": "Cancer medicine", "volume": "14", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "A Novel Approach for Cisplatin-Resistant Esophageal Squamous Cell Carcinoma via Amino Acid Transporter LAT1 Inhibition.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "SIGNIFICANCE: Three-dimensional (3D) two-photon patterned illumination using a combination of computer-generated holography (CGH) and wide-field temporal focusing (TF) has emerged as a highly effective approach for photostimulation. However, even though the axial full-width at half-maximum of a single-spot by TF is smaller than the single-cell size of 10  μm , the axial resolution of 3D multispot patterns produced by CGH with TF is lower than the single-cell resolution as a result of interference among multispots. AIM: We aim to achieve 3D two-photon patterned illumination with single-cell resolution by combining CGH with time-multiplexed multiline temporal focusing (TM-ML-TF), which is implemented by adding an echelle grating at a position conjugate to the focal plane of the TF-CGH system. APPROACH: We measure the 3D two-photon fluorescence distributions generated by the TF-CGH and TM-ML-TF-CGH systems. RESULTS: In TM-ML-TF, the crosstalk artifacts between the target spots in two proximal planes with an axial distance of 20  μm were suppressed from 81% to 15% compared with those in TF. We successfully achieved the photoconversion of 3D target cells in spheroids with single-cell resolution. CONCLUSIONS: TM-ML-TF successfully suppresses the interference among multispots, enabling the TM-ML-TF-CGH system to provide precise 3D patterned illumination with single-cell resolution.", "classifications": [ { "id": "JPMJCR1921", "label": "JPMJCR1921", "researcher": "Itaru Imayoshi", "type": "grant" }, { "id": "Imayoshi", "label": "Group Imayoshi", "parent": "Imayoshi", "type": "group" }, { "id": "Isobe", "label": "Group Isobe", "parent": "Imayoshi", "type": "group" }, { "id": "Imayoshi", "label": "Team Imayoshi", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Kenta", "last_name": "Inazawa", "name": null }, { "creator_type": "author", "first_name": "Mayumi", "last_name": "Yamada", "name": null }, { "creator_type": "author", "first_name": "Takayuki", "last_name": "Michikawa", "name": null }, { "creator_type": "author", "first_name": "Kana", "last_name": "Namiki", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Miyawaki", "name": null }, { "creator_type": "author", "first_name": "Itaru", "last_name": "Imayoshi", "name": null }, { "creator_type": "author", "first_name": "Katsumi", "last_name": "Midorikawa", "name": null }, { "creator_type": "author", "first_name": "Keisuke", "last_name": "Isobe", "name": null } ], "identifiers": { "doi": { "normalized": "10.1117/1.jbo.30.7.075003" }, "pmcid": { "normalized": "PMC12302995" }, "pmid": { "normalized": "40726593" } }, "mesh": [ { "descriptor": "Equipment Design", "descriptor_ui": "D004867", "major_topic": false }, { "descriptor": "Holography", "descriptor_ui": "D006696", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Imaging, Three-Dimensional", "descriptor_ui": "D021621", "major_topic": true }, { "descriptor": "Microscopy, Fluorescence, Multiphoton", "descriptor_ui": "D036641", "major_topic": true }, { "descriptor": "Single-Cell Analysis", "descriptor_ui": "D059010", "major_topic": true } ], "publication": { "conference_name": null, "date": "2025 Jul", "date_precision": "unknown", "issue": "7", "normalized_date": null, "pages": "075003", "proceedings_title": null, "publisher": "", "title": "Journal of biomedical optics", "volume": "30", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Three-dimensional scanless patterned illumination using time-multiplexed multiline temporal focusing for multicell manipulation with single-cell resolution.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Background Graft-versus-host disease (GVHD) is a severe complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Although calcineurin inhibitor (CNI)-containing GVHD prophylaxis is currently standard, it has the disadvantages of nephrotoxicity, a risk for thrombotic microangiopathy, drug interaction, and a requirement for monitoring blood concentration. Therefore, we conducted a prospective trial with the Japanese population undergoing allo-HSCT from an HLA-matched donor to investigate the safety and preliminary efficacy of single-agent post-transplant cyclophosphamide (PTCy) for GVHD prophylaxis. Methods This single-center phase I/II trial was a prospective study registered in the UMIN Clinical Trials Registry (UMINID: UMIN000028779) on November 1, 2017, and enrolled patients aged 16-60 years old with hematological malignancies in remission but without a history of previous allo-HSCT. Myeloablative conditioning (fludarabine 120 mg/m(2) and total body irradiation 12 Gy) was followed by bone marrow transplantation from an HLA-matched donor. Cyclophosphamide (50 mg/kg) was administered on days 3 and 4. The primary endpoint was GVHD-free, relapse-free survival (GRFS) at six months after transplantation. Secondary endpoints included overall survival, incidences of relapse, non-relapse mortality (NRM), and acute and chronic GVHD (a/cGVHD). The prespecified sample size was 20. Results Four patients were enrolled, and one patient withdrew due to medication non-compliance. The GRFS at six months post-transplant was 2 out of 3 evaluable patients (66.7%). Grade 2 aGVHD was observed in 2/3 (66.7%), and neither grade 3-4 aGVHD nor moderate-to-severe cGVHD appeared within six months after transplantation. Two patients required additional cyclosporine administration because of hemophagocytic lymphohistiocytosis and grade 2 skin aGVHD, respectively, which improved promptly after cyclosporine administration. One patient relapsed, and NRM was not observed. Overall survival at six months was 3/3 (100%). The study was terminated early with poor recruitment. Conclusions PTCy alone may ensure safety, but PTCy alone may ensure safety. However, in this small cohort, PTCy monotherapy failed to provide adequate immunosuppression, necessitating CNI-based therapy in two of three patients for immune-mediated complications. Consistent with prior studies in HLA-matched settings that have not shown superiority of PTCy monotherapy over PTCy plus CNI, GVHD prophylaxis with single-agent PTCy should be carefully considered.", "classifications": [ { "id": "Nishikii", "label": "Group Nishikii", "parent": "Shintaku", "type": "group" }, { "id": "Shintaku", "label": "Team Shintaku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Miki", "last_name": "Joyce", "name": null }, { "creator_type": "author", "first_name": "Naoki", "last_name": "Kurita", "name": null }, { "creator_type": "author", "first_name": "Bryan J.", "last_name": "Mathis", "name": null }, { "creator_type": "author", "first_name": "Kenichi", "last_name": "Makishima", "name": null }, { "creator_type": "author", "first_name": "Sakurako", "last_name": "Suma", "name": null }, { "creator_type": "author", "first_name": "Yuya", "last_name": "Sasaki", "name": null }, { "creator_type": "author", "first_name": "Yasuhito", "last_name": "Suehara", "name": null }, { "creator_type": "author", "first_name": "Keiichiro", "last_name": "Hattori", "name": null }, { "creator_type": "author", "first_name": "Tatsuhiro", "last_name": "Sakamoto", "name": null }, { "creator_type": "author", "first_name": "Takayasu", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Naoshi", "last_name": "Obara", "name": null }, { "creator_type": "author", "first_name": "Shigeru", "last_name": "Chiba", "name": null }, { "creator_type": "author", "first_name": "Hidekazu", "last_name": "Nishikii", "name": null }, { "creator_type": "author", "first_name": "Mamiko", "last_name": "Sakata-Yanagimoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.7759/cureus.100251" }, "pmcid": { "normalized": "PMC12840819" }, "pmid": { "normalized": "41607955" } }, "mesh": [], "publication": { "conference_name": null, "date": "2025 Dec", "date_precision": "unknown", "issue": "12", "normalized_date": null, "pages": "e100251", "proceedings_title": null, "publisher": "", "title": "Cureus", "volume": "17", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Safety of Post-transplant Cyclophosphamide as a Single Agent for Graft-Versus-Host Disease Prophylaxis After Human Leukocyte Antigen (HLA)-Matched Transplantation With the Japanese Population: A Single-Center Phase Ⅰ/Ⅱ Study.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "OBJECTIVE: To evaluate whether results of the JCOG0802/WJOG4607L trial, which demonstrated the superiority of segmentectomy over lobectomy in terms of overall survival for patients with peripheral small-sized lung cancer, are applicable to clinical practice. METHODS: In this single-center retrospective analysis, we categorized patients who underwent lobectomy or segmentectomy during the enrollment period of the JCOG0802/WJOG4607L trial into 3 groups: patients enrolled in the trial (Cohort A), patients who were eligible but not enrolled (Cohort B), and ineligible patients (Cohort C). We assessed whether trial participants reflected typical patients seen in clinical practice (representativeness) and whether trial results could be applied in routine practice (generalizability) by comparing patient characteristics and survival between cohorts, using Cohort A as the reference. RESULTS: Cohorts A, B, and C included 91, 163, and 81 patients, respectively. Overall survival at 5 years was 91.2% (95% confidence interval [CI], 83.1%-95.5%), 93.9% (95% CI, 88.5%-96.8%), and 87.7% (95% CI, 77.7%-93.4%), respectively, with no significant different among the 3 cohorts (P = .269). Hazard ratios for segmentectomy over lobectomy were 0.125 (95% CI, 0.015-0.987) in Cohort A, 0.281 (95% CI, 0.036-2.147) in Cohort B, and 1.806 (95% CI, 0.573-5.690) in Cohort C, indicating that the results observed in Cohort A were not replicated in Cohort B. CONCLUSIONS: In this single-center retrospective study, segmentectomy was associated with numerically improved overall survival rates than lobectomy in JCOG0802-eligible patients not enrolled in the trial, although the difference was not statistically significant. Given the study's retrospective nature and underpowered statistics with a small sample size, these findings should be interpreted cautiously.", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Tsuchida", "name": null }, { "creator_type": "author", "first_name": "Masaya", "last_name": "Yotsukura", "name": null }, { "creator_type": "author", "first_name": "Tomohiro", "last_name": "Haruki", "name": null }, { "creator_type": "author", "first_name": "Yukihiro", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Kimiteru", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Hirokazu", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Tomonori", "last_name": "Mizutani", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null }, { "creator_type": "author", "first_name": "Shun-Ichi", "last_name": "Watanabe", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.xjon.2025.05.005" }, "pmcid": { "normalized": "PMC12414405" }, "pmid": { "normalized": "40923055" } }, "mesh": [], "publication": { "conference_name": null, "date": "2025 Aug", "date_precision": "unknown", "issue": "", "normalized_date": null, "pages": "234-241", "proceedings_title": null, "publisher": "", "title": "JTCVS open", "volume": "26", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Is segmentectomy actually superior to lobectomy for early-stage lung cancer? A discrepancy between the JCOG0802 trial and real-world practice.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "", "classifications": [ { "id": "Hamamoto", "label": "Group Hamamoto", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Takeshi", "last_name": "Uozumi", "name": null }, { "creator_type": "author", "first_name": "Maki", "last_name": "Sugimoto", "name": null }, { "creator_type": "author", "first_name": "Yasuhiko", "last_name": "Mizuguchi", "name": null }, { "creator_type": "author", "first_name": "Naoya", "last_name": "Toyoshima", "name": null }, { "creator_type": "author", "first_name": "Seiichiro", "last_name": "Abe", "name": null }, { "creator_type": "author", "first_name": "Ryuji", "last_name": "Hamamoto", "name": null }, { "creator_type": "author", "first_name": "Yutaka", "last_name": "Saito", "name": null } ], "identifiers": { "doi": { "normalized": "10.1055/a-2639-4693" }, "pmcid": { "normalized": "PMC12367403" }, "pmid": { "normalized": "40834891" } }, "mesh": [], "publication": { "conference_name": null, "date": "2025 Dec", "date_precision": "unknown", "issue": "S 01", "normalized_date": null, "pages": "E923-E924", "proceedings_title": null, "publisher": "", "title": "Endoscopy", "volume": "57", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Intraoperative mixed reality support for endoscopic submucosal dissection of a large laterally spreading tumor in the rectum.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "During embryogenesis, organisms function as a robust system that ensures uniformity within individuals, but they lose robustness and develop variations at advanced ages. However, when and how organisms lose this robustness remains largely elusive. Here, we identified a sharp transition from interindividual uniformity to diversity in the appearance and transcriptional features of age-matched Caenorhabditis elegans in midlife. Convolutional neural network analysis of individual appearance alterations revealed that the transition occurs in midlife, which coincides with the cessation of egg-laying activity and increased motility defects. This period represents the transition from the young state, marked by shared homogeneous features among same-age individuals, to the old state, marked by shared among old individuals. Transcriptional coherence within the age-matched individuals shows essentially the same transition, coinciding with the appearance features. These findings provide a new framework for understanding the aging trajectory in C. elegans, demonstrating the occurrence of the loss of robust control over appearance and transcriptional homeostasis in midlife.", "classifications": [ { "id": "Yamamoto", "label": "Group Yamamoto", "parent": "Toyoshima", "type": "group" }, { "id": "Toyoshima", "label": "Team Toyoshima", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Masaharu", "last_name": "Uno", "name": null }, { "creator_type": "author", "first_name": "Masanori", "last_name": "Nono", "name": null }, { "creator_type": "author", "first_name": "Chika", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Saya", "last_name": "Kishimoto", "name": null }, { "creator_type": "author", "first_name": "Emiko", "last_name": "Okabe", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Eisuke", "last_name": "Nishida", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/gtc.13187" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "39743742" } }, "mesh": [ { "descriptor": "Aging", "descriptor_ui": "D000375", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Caenorhabditis elegans", "descriptor_ui": "D017173", "major_topic": true }, { "descriptor": "Caenorhabditis elegans Proteins", "descriptor_ui": "D029742", "major_topic": false }, { "descriptor": "Transcription, Genetic", "descriptor_ui": "D014158", "major_topic": false } ], "publication": { "conference_name": null, "date": "2025 Jan", "date_precision": "unknown", "issue": "1", "normalized_date": null, "pages": "e13187", "proceedings_title": null, "publisher": "", "title": "Genes to cells : devoted to molecular & cellular mechanisms", "volume": "30", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "A Transition From Interindividual Uniformity to Diversity in Appearance and Transcriptional Features at Midlife in Caenorhabditis elegans.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BackgroundEarly detection of dementia requires highly accurate and efficient screening tests that minimize patient burden.ObjectiveTo develop a machine learning model predicting dementia conversion within 3-5 years using Cube Copying Test (CCT) drawings at baseline.MethodsThis retrospective study analyzed CCT drawing data from 767 patients at the Center for Comprehensive Care and Research on Memory Disorders (2011-2020). Of the 2303 patients who met the inclusion criteria, 534 were excluded due to mild cognitive impairment (MCI) persistence, pending diagnoses, or new neurovascular diseases, while 1002 were lost to follow-up. Eligibility criteria included a baseline Mini-Mental State Examination (MMSE) score ≥24, absence of dementia diagnosis or anti-dementia medication intake, and completion of a 3-5-year follow-up without meeting exclusion criteria.ResultsOf 767 patients, 457 converted to dementia (318 with Alzheimer's disease, 116 with dementia with Lewy bodies, and 23 with frontotemporal dementia) within 3-5 years, while 310 did not. The model achieved an area under the curve of 0.85 for predicting dementia conversion. Shapley Additive exPlanations analysis identified PatchCore-derived features as the strongest predictors, distinguishing drawing patterns of converters and non-converters.ConclusionsIn patients who convert to Alzheimer's disease, dementia with Lewy bodies, or frontotemporal dementia, the very early stages of constructional apraxia-like symptoms already exist at the preclinical stage or MCI stage. Applying deep learning-based anomaly-detection models can detect these early drawing distortions that differ from normal aging and contribute to improving the performance of dementia-conversion prediction.", "classifications": [ { "id": "Suzuki", "label": "Group Suzuki", "parent": "Takekawa", "type": "group" }, { "id": "Takekawa", "label": "Team Takekawa", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Mio", "last_name": "Shinozaki", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Hishida", "name": null }, { "creator_type": "author", "first_name": "Yasuyuki", "last_name": "Gondo", "name": null }, { "creator_type": "author", "first_name": "Michio", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Rina", "last_name": "Miura", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Sakurai", "name": null }, { "creator_type": "author", "first_name": "Akinori", "last_name": "Takeda", "name": null }, { "creator_type": "author", "first_name": "Yutaka", "last_name": "Arahata", "name": null } ], "identifiers": { "doi": { "normalized": "10.1177/13872877251376939" }, "pmcid": { "normalized": "PMC12583638" }, "pmid": { "normalized": "40982217" } }, "mesh": [ { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Aged, 80 and over", "descriptor_ui": "D000369", "major_topic": false }, { "descriptor": "Alzheimer Disease", "descriptor_ui": "D000544", "major_topic": false }, { "descriptor": "Cognitive Dysfunction", "descriptor_ui": "D060825", "major_topic": false }, { "descriptor": "Dementia", "descriptor_ui": "D003704", "major_topic": true }, { "descriptor": "Disease Progression", "descriptor_ui": "D018450", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Frontotemporal Dementia", "descriptor_ui": "D057180", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Lewy Body Disease", "descriptor_ui": "D020961", "major_topic": false }, { "descriptor": "Machine Learning", "descriptor_ui": "D000069550", "major_topic": true }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mental Status and Dementia Tests", "descriptor_ui": "D000073216", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Neuropsychological Tests", "descriptor_ui": "D009483", "major_topic": true }, { "descriptor": "Retrospective Studies", "descriptor_ui": "D012189", "major_topic": false } ], "publication": { "conference_name": null, "date": "2025 Nov", "date_precision": "unknown", "issue": "1_suppl", "normalized_date": null, "pages": "S141-S158", "proceedings_title": null, "publisher": "", "title": "Journal of Alzheimer's disease : JAD", "volume": "108", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Machine learning model for predicting the conversion to dementia using the Cube Copying Test.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Intravascular large B-cell lymphoma (IVLBCL) is a rare type of extranodal large B-cell lymphoma that is characterized by the proliferation of lymphoma cells in the lumina of small vessels. Recent progress uncovering the genetic characteristics associated with MYD88/CD79B mutations has stimulated interest in the use of drugs targeting B-cell receptor signaling, including Bruton's tyrosine kinase. However, difficulties in culturing ex vivo IVLBCL cells has hampered research on the development of novel therapies. In the present study, we demonstrated the establishment of an ex vivo culture system of IVLBCL cells obtained from patient-derived xenograft (PDX) models. The spheroid culture enabled us to culture IVLBCL PDX cells for more than 10 days and to explore the efficacy of drug treatments acting on these cells. We found that carfilzomib and ibrutinib were effective for treating IVLBCL in ex vivo experiments and conducted in vivo analyses to assess the efficacy of these drugs. Although the efficacy of carfilzomib was difficult to confirm due to its toxicity in our models, ibrutinib showed comparable efficacy to a standard combination of chemotherapy drugs. Together, our data provide a new culture method for IVLBCL PDX cells and a rationale for translating ibrutinib to clinical use in IVLBCL patients.", "classifications": [ { "id": "Suzuki", "label": "Group Suzuki", "parent": "Takekawa", "type": "group" }, { "id": "Takekawa", "label": "Team Takekawa", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Mika", "last_name": "Takai", "name": null }, { "creator_type": "author", "first_name": "Kazuyuki", "last_name": "Shimada", "name": null }, { "creator_type": "author", "first_name": "Katsuya", "last_name": "Furukawa", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Yamaga", "name": null }, { "creator_type": "author", "first_name": "Soichi", "last_name": "Yoshiyama", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Kagaya", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Kazuhiko", "last_name": "Hayashi", "name": null }, { "creator_type": "author", "first_name": "Satoko", "last_name": "Shimada", "name": null }, { "creator_type": "author", "first_name": "Kennosuke", "last_name": "Karube", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Kiyoi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/cas.16310" }, "pmcid": { "normalized": "PMC11711046" }, "pmid": { "normalized": "39428323" } }, "mesh": [ { "descriptor": "Adenine", "descriptor_ui": "D000225", "major_topic": true }, { "descriptor": "Agammaglobulinaemia Tyrosine Kinase", "descriptor_ui": "D000077329", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Antineoplastic Agents", "descriptor_ui": "D000970", "major_topic": false }, { "descriptor": "CD79 Antigens", "descriptor_ui": "D051925", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Lymphoma, Large B-Cell, Diffuse", "descriptor_ui": "D016403", "major_topic": true }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred NOD", "descriptor_ui": "D016688", "major_topic": false }, { "descriptor": "Myeloid Differentiation Factor 88", "descriptor_ui": "D053594", "major_topic": false }, { "descriptor": "Oligopeptides", "descriptor_ui": "D009842", "major_topic": false }, { "descriptor": "Piperidines", "descriptor_ui": "D010880", "major_topic": true }, { "descriptor": "Pyrazoles", "descriptor_ui": "D011720", "major_topic": false }, { "descriptor": "Pyrimidines", "descriptor_ui": "D011743", "major_topic": false }, { "descriptor": "Spheroids, Cellular", "descriptor_ui": "D018874", "major_topic": true }, { "descriptor": "Tumor Cells, Cultured", "descriptor_ui": "D014407", "major_topic": false }, { "descriptor": "Vascular Neoplasms", "descriptor_ui": "D019043", "major_topic": false }, { "descriptor": "Xenograft Model Antitumor Assays", "descriptor_ui": "D023041", "major_topic": true } ], "publication": { "conference_name": null, "date": "2025 Jan", "date_precision": "unknown", "issue": "1", "normalized_date": null, "pages": "214-225", "proceedings_title": null, "publisher": "", "title": "Cancer science", "volume": "116", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Spheroid culture to select theoretical therapeutic drugs in intravascular large B-cell lymphoma.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Roxadustat, a drug recently approved for treating renal anemia, might activate thyroid hormone receptors (TRα and TRβ). We, thus, investigated the direct effects of roxadustat on intact TRα and TRβ in vitro. U2OS, MCF-7, COS-7, and Caco-2 cells were transiently transfected with a firefly luciferase reporter plasmid highly responsive to the activation of TRα and TRβ, along with a plasmid overexpressing either TRα or TRβ. Transfected cells were incubated for three hours in 100% thyroid hormone-stripped fetal bovine serum (FBS) with or without either roxadustat or triiodothyronine (T3). Also, transfected U2OS cells were placed for three hours in 100% unprocessed normal adult human serum with or without the addition of either roxadustat or T3. Cell lysates were measured for firefly luciferase activity. Roxadustat induced firefly luciferase activities when added at clinically achievable serum concentrations in TRα- or TRβ-transfected U2OS, MCF-7, COS-7, and Caco-2 cells placed in thyroid hormone-deprived FBS. The induction was comparable to or greater than that observed with T3 added at normal or even supranormal serum concentrations. Roxadustat also increased firefly luciferase activities in TRα- or TRβ-transfected U2OS cells in adult human serum. These data suggest the possibility that roxadustat could activate TRα and TRβ at clinically relevant concentrations. Physicians prescribing roxadustat should be aware of its thyromimetic activity.", "classifications": [ { "id": "Suzuki", "label": "Group Suzuki", "parent": "Takekawa", "type": "group" }, { "id": "Takekawa", "label": "Team Takekawa", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Koji", "last_name": "Morita", "name": null }, { "creator_type": "author", "first_name": "Toru", "last_name": "Iigo", "name": null }, { "creator_type": "author", "first_name": "Kaho", "last_name": "Jimbo", "name": null }, { "creator_type": "author", "first_name": "Akihiro", "last_name": "Jimbo", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Naoki", "last_name": "Edo", "name": null }, { "creator_type": "author", "first_name": "Hiroki", "last_name": "Yamazaki", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Uno", "name": null }, { "creator_type": "author", "first_name": "Kazuhisa", "last_name": "Tsukamoto", "name": null }, { "creator_type": "author", "first_name": "Toshio", "last_name": "Ishikawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.7759/cureus.89750" }, "pmcid": { "normalized": "PMC12421935" }, "pmid": { "normalized": "40937255" } }, "mesh": [], "publication": { "conference_name": null, "date": "2025 Aug", "date_precision": "unknown", "issue": "8", "normalized_date": null, "pages": "e89750", "proceedings_title": null, "publisher": "", "title": "Cureus", "volume": "17", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Roxadustat Activates Thyroid Hormone Receptors α and β at Clinically Relevant Concentrations.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Pattern dynamics on curved surfaces are ubiquitous. Although the effect of surface topography on pattern dynamics has gained much interest, there is a limited understanding of the roles of surface geometry and topology in pattern dynamics. Recently, we reported that a static pattern on a flat plane can become a propagating pattern on a curved surface [Phys. Rev. Lett. 128, 224101 (2022)10.1103/PhysRevLett.128.224101]. By examining reaction-diffusion equations on axisymmetric surfaces, certain conditions for the onset of pattern propagation were determined. However, this analysis was limited by the assumption that the pattern propagates at a constant speed. Here, we investigate the pattern propagation driven by surface curvature using weakly nonlinear analysis, which enables a more comprehensive approach to the aforementioned problem. The analysis reveals consistent conditions of the pattern propagation similar to our previous results, and further predicts that rich dynamics other than pattern propagation, such as periodic and chaotic behaviors, can arise depending on the surface geometry. This study provides a perspective on the relationship between surfaces and pattern dynamics and a basis for controlling pattern dynamics on surfaces.", "classifications": [ { "id": "Ishihara", "label": "Group Ishihara", "parent": "Sawai", "type": "group" }, { "id": "Sawai", "label": "Team Sawai", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Ryosuke", "last_name": "Nishide", "name": null }, { "creator_type": "author", "first_name": "Shuji", "last_name": "Ishihara", "name": null } ], "identifiers": { "doi": { "normalized": "10.1103/physreve.111.024208" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "40103169" } }, "mesh": [], "publication": { "conference_name": null, "date": "2025 Feb", "date_precision": "unknown", "issue": "2-1", "normalized_date": null, "pages": "024208", "proceedings_title": null, "publisher": "", "title": "Physical review. E", "volume": "111", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Weakly nonlinear analysis of Turing pattern dynamics on curved surfaces.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Patients with mpox may present with a skin rash and mild respiratory symptoms, including sore throat and cough. The genome of the mpox virus (MPXV) has been detected in throat swab specimens from some mpox patients, indicating potential involvement of the respiratory tract. In this study, we used lung organoids to investigate the effects of MPXV infection on the respiratory system by evaluating the viral replication and the infection-mediated host response. MPXV infection resulted in the accumulation of high levels of viral genomes within the cells. H&E staining showed almost no histological differences between MPXV-infected lung organoids and uninfected lung organoids. In addition, RNA-seq analysis revealed that MPXV infection did not significantly alter the gene expression levels of various lung markers. MPXV infection did not change the production of proinflammatory cytokines, including interleukin-1 beta (IL-1beta), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), and interferon-beta (IFN-beta). These findings suggest that MPXV can replicate in lung organoids without significantly affecting their cellular function.", "classifications": [ { "id": "Yamamoto", "label": "Group Yamamoto", "parent": "Toyoshima", "type": "group" }, { "id": "Toyoshima", "label": "Team Toyoshima", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yoshitaka", "last_name": "Nakata", "name": null }, { "creator_type": "author", "first_name": "Keiya", "last_name": "Uriu", "name": null }, { "creator_type": "author", "first_name": "Rina", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Akatsuki", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Kei", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Kazuo", "last_name": "Takayama", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.bbrep.2025.102326" }, "pmcid": { "normalized": "PMC12803792" }, "pmid": { "normalized": "41542170" } }, "mesh": [], "publication": { "conference_name": null, "date": "2025 Dec", "date_precision": "unknown", "issue": "", "normalized_date": null, "pages": "102326", "proceedings_title": null, "publisher": "", "title": "Biochemistry and biophysics reports", "volume": "44", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Mpox virus replicates in lung organoids without significantly affecting their cellular function.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: Schlafen 11 (SLFN-11) has been identified as a sensitizer of tumor cells to DNA-damaging agents. However, the relationship between SLFN-11 expression and clinical outcomes in patients with small cell lung cancer (SCLC) remains unexplored. Thus, we aimed to evaluate the impact of SLFN-11 expression on survival in patients with limited-stage (LS) SCLC. METHODS: We conducted a retrospective review of data from patients pathologically diagnosed with LS-SCLC post-surgery between January 2008 and December 2018. SLFN-11 expression was assessed using immunohistochemistry in tissue microarrays and scored using a histology (H)-score (range: 0-300). RESULTS: Overall, 86 patients were included in the analysis with a median H-score of 43 for SLFN-11 expression. Among the patients, 44 had high SLFN-11 expression (provisionally defined as H-score >/= 43). No significant differences in clinical profiles were observed between the two groups (high and low SLFN expression). The median survival durations were not reached (NR; 95% confidence interval [CI]: 65.1 months to NR) and 33.5 months (95% CI: 24.2 months to NR) for patients with high and low SLFN-11 expression, respectively (hazard ratio [HR]: 0.40, 95% CI: 0.19-0.81; p = 0.012). Among patients who relapsed post-surgery (n = 21), the median survival durations were 22.0 (95% CI: 7.6-44.9 months) and 8.1 (95% CI: 1.8-24.6 months) months in patients with high and low SLFN-11 expression, respectively (HR: 0.22, 95% CI: 0.06-0.84; p = 0.026). CONCLUSIONS: High SLFN-11 expression is associated with relatively longer survival in patients with LS-SCLC in both those undergoing surgery and those who have relapsed.", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Ken", "last_name": "Masuda", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Noriko", "last_name": "Motoi", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Shinno", "name": null }, { "creator_type": "author", "first_name": "Yuji", "last_name": "Matsumoto", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Okuma", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Goto", "name": null }, { "creator_type": "author", "first_name": "Hidehito", "last_name": "Horinouchi", "name": null }, { "creator_type": "author", "first_name": "Noboru", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Shun-Ichi", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Tomoaki", "last_name": "Hoshino", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null }, { "creator_type": "author", "first_name": "Yuichiro", "last_name": "Ohe", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/1759-7714.15529" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "39809728" } }, "mesh": [ { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Aged, 80 and over", "descriptor_ui": "D000369", "major_topic": false }, { "descriptor": "Biomarkers, Tumor", "descriptor_ui": "D014408", "major_topic": true }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Lung Neoplasms", "descriptor_ui": "D008175", "major_topic": true }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Nuclear Proteins", "descriptor_ui": "D009687", "major_topic": false }, { "descriptor": "Prognosis", "descriptor_ui": "D011379", "major_topic": false }, { "descriptor": "Retrospective Studies", "descriptor_ui": "D012189", "major_topic": false }, { "descriptor": "Small Cell Lung Carcinoma", "descriptor_ui": "D055752", "major_topic": true } ], "publication": { "conference_name": null, "date": "2025 Jan", "date_precision": "unknown", "issue": "1", "normalized_date": null, "pages": "e15529", "proceedings_title": null, "publisher": "", "title": "Thoracic cancer", "volume": "16", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Schlafen 11 Expression in Patients With Small Cell Lung Cancer and Its Association With Clinical Outcomes.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "5'Hox genes regulate pattern formation along the axes of the limb. Previously, we showed that Hoxa13/Hoxd13 double-mutant newts lacked all digits of the forelimbs during development and regeneration, showing that newt Hox13 is necessary for digit formation in development and regeneration. In addition, we found another unique phenotype. Some of the Hox13 crispant newts showed hindlimb defects, in which whole or almost whole hindlimbs were lost, suggesting a novel function of Hox13 in limb development. Using germline mutants, we showed that mutation in Hox13 led to hindlimb defects. The limb buds of Hox13 crispants formed, however, did not show outgrowth. Expression of Fgf10 and Tbx4, which are involved in limb outgrowth, decreased in the hindlimb buds of Hox13 crispants. In addition, hindlimb defects were observed in both Fgf10 and Tbx4 crispant newts. Finally, Fgf10 and Tbx4 interacted with Hox13 genetically. Our results revealed a novel function of Hox13 in regulating the outgrowth of the newt hindlimb bud through interaction with Fgf10 and Tbx4.", "classifications": [ { "id": "Suzuki", "label": "Group Suzuki", "parent": "Morishita", "type": "group" }, { "id": "Morishita", "label": "Team Morishita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Sayo", "last_name": "Tozawa", "name": null }, { "creator_type": "author", "first_name": "Haruka", "last_name": "Matsubara", "name": null }, { "creator_type": "author", "first_name": "Fumina", "last_name": "Minamitani", "name": null }, { "creator_type": "author", "first_name": "Yasuhiro", "last_name": "Kamei", "name": null }, { "creator_type": "author", "first_name": "Misako", "last_name": "Saida", "name": null }, { "creator_type": "author", "first_name": "Momoko", "last_name": "Asao", "name": null }, { "creator_type": "author", "first_name": "Ken-Ichi T.", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Masatoshi", "last_name": "Matsunami", "name": null }, { "creator_type": "author", "first_name": "Shuji", "last_name": "Shigenobu", "name": null }, { "creator_type": "author", "first_name": "Toshinori", "last_name": "Hayashi", "name": null }, { "creator_type": "author", "first_name": "Gembu", "last_name": "Abe", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Takeuchi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/dgd.12952" }, "pmcid": { "normalized": "PMC11758191" }, "pmid": { "normalized": "39725403" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Fibroblast Growth Factor 10", "descriptor_ui": "D051526", "major_topic": true }, { "descriptor": "Gene Expression Regulation, Developmental", "descriptor_ui": "D018507", "major_topic": false }, { "descriptor": "Hindlimb", "descriptor_ui": "D006614", "major_topic": true }, { "descriptor": "Homeodomain Proteins", "descriptor_ui": "D018398", "major_topic": true }, { "descriptor": "Limb Buds", "descriptor_ui": "D018878", "major_topic": true }, { "descriptor": "Salamandridae", "descriptor_ui": "D012455", "major_topic": true }, { "descriptor": "T-Box Domain Proteins", "descriptor_ui": "D020825", "major_topic": true } ], "publication": { "conference_name": null, "date": "2025 Jan", "date_precision": "unknown", "issue": "1", "normalized_date": null, "pages": "10-22", "proceedings_title": null, "publisher": "", "title": "Development, growth & differentiation", "volume": "67", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Novel function of Hox13 in regulating outgrowth of the newt hindlimb bud through interaction with Fgf10 and Tbx4.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Patterns on curved surfaces are ubiquitous, yet the influence of surface geometry on pattern dynamics remains elusive. We recently reported a mechanism of pattern propagation in which a static pattern on a flat plane becomes a propagating pattern on a curved surface [Phys. Rev. Lett. 128, 224101 (2022)0031-900710.1103/PhysRevLett.128.224101]. Here, we address whether surface curvature can drive more complex pattern dynamics beyond propagation. By employing a combination of weakly nonlinear analysis and numerical simulation, we theoretically determine the condition for the emergence of pattern dynamics on curved surfaces and show that oscillatory and chaotic pattern dynamics can emerge by controlling the surface shapes. These findings highlight a role of surface topography in pattern formation and dynamics.", "classifications": [ { "id": "Ishihara", "label": "Group Ishihara", "parent": "Sawai", "type": "group" }, { "id": "Sawai", "label": "Team Sawai", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Ryosuke", "last_name": "Nishide", "name": null }, { "creator_type": "author", "first_name": "Shuji", "last_name": "Ishihara", "name": null } ], "identifiers": { "doi": { "normalized": "10.1103/physreve.111.l022202" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "40103164" } }, "mesh": [], "publication": { "conference_name": null, "date": "2025 Feb", "date_precision": "unknown", "issue": "2", "normalized_date": null, "pages": "L022202", "proceedings_title": null, "publisher": "", "title": "Physical review. E", "volume": "111", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Oscillatory and chaotic pattern dynamics driven by surface curvature.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "INTRODUCTION: Minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS) are podocytopathies with varying clinical courses and therapeutic responses. FSGS often leads to end-stage renal disease. Consequently, their heterogeneity requires case stratification and pathophysiological elucidation. The involvement of energy metabolism in FSGS pathogenesis and stratification has not been clarified. Therefore, this study aimed to verify whether evaluating energy kinetics can be a new approach to MCD or FSGS stratification and explore the role of energy metabolism in MCD or FSGS. METHODS: Cultured human podocytes were treated with sera from patients with biopsy-confirmed MCD or FSGS. Serum-treated podocytes were analyzed for apoptosis using flow cytometry, metabolomics via mass spectrometry, and real-time adenosine triphosphate (ATP) production rates using an extracellular flux analyzer. Adriamycin-induced nephropathy was induced in podocyte-specific lactate dehydrogenase (LDH) A (LDHA)-deficient and control mice. RESULTS: The sera from patients with FSGS significantly induced apoptosis in human podocytes compared with those from individuals with MCD. Apoptosis severity was associated with segmental obliteration and corticosteroid resistance. Metabolomic analysis revealed differences in anaerobic glycolysis and tricarboxylic acid cycle (TCA)-related metabolites in podocytes exposed to the sera of patients with MCD and FSGS. In the podocytes treated with sera from patients with FSGS, glycolytic ATP production significantly decreased in cases with high apoptosis rates. The sera from patients with FSGS suppressed LDHA activity, suppressed alpha-actinin 4 (ACTN4) expression, and promoted actin remodeling of podocytes. Segmental sclerosis was more prominent in podocyte-specific LDHA-deficient mice with adriamycin-induced nephropathy than in control mice. CONCLUSION: FSGS progression was associated with decreased anaerobic glycolysis in podocytes.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Masahiro", "last_name": "Sugimura", "name": null }, { "creator_type": "author", "first_name": "Kayaho", "last_name": "Maeda", "name": null }, { "creator_type": "author", "first_name": "Katsuaki", "last_name": "Shibata", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Seko", "name": null }, { "creator_type": "author", "first_name": "Yohei", "last_name": "Kozaki", "name": null }, { "creator_type": "author", "first_name": "Akiyoshi", "last_name": "Hirayama", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Takaya", "last_name": "Ozeki", "name": null }, { "creator_type": "author", "first_name": "Yuka", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Noritoshi", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Tomoki", "last_name": "Kosugi", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Kadomatsu", "name": null }, { "creator_type": "author", "first_name": "Shoichi", "last_name": "Maruyama", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.ekir.2025.06.022" }, "pmcid": { "normalized": "PMC12446983" }, "pmid": { "normalized": "40980659" } }, "mesh": [], "publication": { "conference_name": null, "date": "2025 Sep", "date_precision": "unknown", "issue": "9", "normalized_date": null, "pages": "3239-3254", "proceedings_title": null, "publisher": "", "title": "Kidney international reports", "volume": "10", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Dysregulated Anaerobic Glycolysis in Podocytes is Relevant to the Progression of Focal Segmental Glomerulosclerosis.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "During mouse embryonic development, the embryonic day (E) 5.5 stage represents a crucial period for the formation of the primitive body axis, where the symmetry breaking of cellular states influences the multicellular system. Elucidating the detailed mechanisms of this process necessitates a trans-layered dynamic observation of the embryo and all internal cells. In this report, we present our success in achieving in-toto single-cell observation in a whole hemisphere of an E5.5 embryo for 12 h, using a newly developed incubator-type biaxial light-sheet microscope. To achieve the success, we optimized our microscope system, including an incubator for culture stability, and refining the observation protocol to reduce phototoxicity. Our key discovery is that the scan speed during light-sheet formation plays a critical role in reducing phototoxicity, rather than the irradiation intensity or the interval time between frames. This innovative system not only enabled in-toto single-cell tracking but also led to the discovery of the abrupt shrinking of embryos whose contractile center was located at the extraembryonic ectoderm during monotonous growth up to the E6.5 stage.", "classifications": [ { "id": "Onami", "label": "Group Onami", "parent": "Fujiwara", "type": "group" }, { "id": "Fujiwara", "label": "Team Fujiwara", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Go", "last_name": "Shioi", "name": null }, { "creator_type": "author", "first_name": "Tomonobu M.", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Junichi", "last_name": "Kaneshiro", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Azuma", "name": null }, { "creator_type": "author", "first_name": "Shuichi", "last_name": "Onami", "name": null } ], "identifiers": { "doi": { "normalized": "10.26508/lsa.202402839" }, "pmcid": { "normalized": "PMC11735545" }, "pmid": { "normalized": "39814551" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Embryo, Mammalian", "descriptor_ui": "D004622", "major_topic": true }, { "descriptor": "Embryonic Development", "descriptor_ui": "D047108", "major_topic": true }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Incubators", "descriptor_ui": "D007185", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Microscopy", "descriptor_ui": "D008853", "major_topic": true }, { "descriptor": "Single-Cell Analysis", "descriptor_ui": "D059010", "major_topic": false } ], "publication": { "conference_name": null, "date": "2025 Mar", "date_precision": "unknown", "issue": "3", "normalized_date": null, "pages": "", "proceedings_title": null, "publisher": "", "title": "Life science alliance", "volume": "8", "year": 2025 }, "ssbd": { "database": [], "repository": [ "ssbd-repos-000243" ] }, "title": "Trans-scale live-imaging of an E5.5 mouse embryo using incubator-type biaxial light-sheet microscopy.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Although ovarian endometrioid carcinoma (OEC), frequently associated with endometrial endometrioid carcinoma (EEC), is often diagnosed at an early stage, the prognosis remains poor. The development of new, effective drugs to target these cancers is highly desirable. The bromodomain and extra-terminal domain (BET) family proteins serve a role in regulating transcription by recognizing histone acetylation, which is implicated in several types of cancer. BET inhibitors have been reported as promising cancer drugs. The present study aimed to assess the role of JQ1, a BET inhibitor, in ovarian and endometrial cancers. The sensitivity of OEC and EEC cell lines to JQ1 was assessed using cell viability and colony formation assays. Additionally, western blotting and cell cycle assays were performed to evaluate changes in c-Myc expression and apoptosis markers. Cell proliferation and colony formation assays revealed significant tumor suppression in both OEC and EEC cell lines in response to JQ1 treatment. Furthermore, treatment with JQ1 induced a decrease in c-Myc expression and an increase in apoptosis markers, such as cleaved PARP and the cell population in the sub-G1 phase, in both OEC and EEC cell lines. The findings of the present study indicate that JQ1 may induce cell death through c-Myc inhibition and could be a potentially novel therapeutic agent in the treatment in OEC and EEC. However, the direct mechanism, has not been fully elucidated, warranting further investigation.", "classifications": [ { "id": "Hamamoto", "label": "Group Hamamoto", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Saki", "last_name": "Tanimoto", "name": null }, { "creator_type": "author", "first_name": "Kenbun", "last_name": "Sone", "name": null }, { "creator_type": "author", "first_name": "Yuri", "last_name": "Jonouchi", "name": null }, { "creator_type": "author", "first_name": "Ryuta", "last_name": "Hachijo", "name": null }, { "creator_type": "author", "first_name": "Eri", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Natsumi", "last_name": "Tsuboyama", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Toyohara", "name": null }, { "creator_type": "author", "first_name": "Futaba", "last_name": "Inoue", "name": null }, { "creator_type": "author", "first_name": "Harunori", "last_name": "Honjoh", "name": null }, { "creator_type": "author", "first_name": "Tomohiko", "last_name": "Fukuda", "name": null }, { "creator_type": "author", "first_name": "Ayumi", "last_name": "Taguchi", "name": null }, { "creator_type": "author", "first_name": "Yuichiro", "last_name": "Miyamoto", "name": null }, { "creator_type": "author", "first_name": "Takayuki", "last_name": "Iriyama", "name": null }, { "creator_type": "author", "first_name": "Mayuyo", "last_name": "Mori", "name": null }, { "creator_type": "author", "first_name": "Ken", "last_name": "Asada", "name": null }, { "creator_type": "author", "first_name": "Masaaki", "last_name": "Komatsu", "name": null }, { "creator_type": "author", "first_name": "Syuzo", "last_name": "Kaneko", "name": null }, { "creator_type": "author", "first_name": "Ryuji", "last_name": "Hamamoto", "name": null }, { "creator_type": "author", "first_name": "Osamu", "last_name": "Wada-Hiraike", "name": null }, { "creator_type": "author", "first_name": "Katsutoshi", "last_name": "Oda", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Hirota", "name": null }, { "creator_type": "author", "first_name": "Yutaka", "last_name": "Osuga", "name": null } ], "identifiers": { "doi": { "normalized": "10.3892/ol.2024.14852" }, "pmcid": { "normalized": "PMC11683525" }, "pmid": { "normalized": "39736925" } }, "mesh": [], "publication": { "conference_name": null, "date": "2025 Mar", "date_precision": "unknown", "issue": "3", "normalized_date": null, "pages": "106", "proceedings_title": null, "publisher": "", "title": "Oncology letters", "volume": "29", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "BET inhibitor JQ1 induces apoptosis of ovarian and endometrial endometrioid carcinoma cells by downregulating c‑Myc.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "SIGNIFICANCE: I explore hyperspectral imaging, a rapid and noninvasive technique with significant potential in biometrics and medical diagnosis. Personal identification was performed using cross-sectional hyperspectral images of palms, offering a simpler and more robust method than conventional vascular pattern identification methods. AIM: I aim to demonstrate the potential of local cross-sectional hyperspectral palm images to identify individuals with high accuracy. APPROACH: Hyperspectral imaging of palms, artificial intelligence (AI)-based region of interest (ROI) detection, feature vector extraction, and dimensionality reduction were utilized to validate personal identification accuracy using the area under the curve (AUC) and equal error rate (EER). RESULTS: The feature vectors extracted by the proposed method demonstrated higher intra-cluster similarity when the clustering data were reduced through uniform manifold approximation and projection compared with principal component analysis and t -distributed stochastic neighbor embedding. A maximum AUC of 0.98 and an EER of 0.04% were observed. CONCLUSIONS: I proposed a biometric method using cross-sectional hyperspectral imaging of human palms. The procedure includes AI-based ROI detection, feature extraction, dimension reduction, and intra- and inter-subject matching using Euclidean distances as a discriminant function. The proposed method has the potential to identify individuals with high accuracy.", "classifications": [ { "id": "Suzuki", "label": "Group Suzuki", "parent": "Takekawa", "type": "group" }, { "id": "Takekawa", "label": "Team Takekawa", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Takashi", "last_name": "Suzuki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1117/1.jbo.30.2.023514" }, "pmcid": { "normalized": "PMC11649094" }, "pmid": { "normalized": "39687234" } }, "mesh": [ { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Algorithms", "descriptor_ui": "D000465", "major_topic": false }, { "descriptor": "Artificial Intelligence", "descriptor_ui": "D001185", "major_topic": false }, { "descriptor": "Biometric Identification", "descriptor_ui": "D056667", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Hand", "descriptor_ui": "D006225", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Hyperspectral Imaging", "descriptor_ui": "D000081862", "major_topic": true }, { "descriptor": "Image Processing, Computer-Assisted", "descriptor_ui": "D007091", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Principal Component Analysis", "descriptor_ui": "D025341", "major_topic": false } ], "publication": { "conference_name": null, "date": "2025 Feb", "date_precision": "unknown", "issue": "2", "normalized_date": null, "pages": "023514", "proceedings_title": null, "publisher": "", "title": "Journal of biomedical optics", "volume": "30", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Personal identification using a cross-sectional hyperspectral image of a hand.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Feeding behavior is controlled by various neural networks in the brain that are involved in different feeding phases: Food procurement, consumption, and termination. However, the specific neural circuits controlling the food consumption phase remain poorly understood. Here, we investigated the roles of dopaminergic neurons in the paraventricular nucleus of the hypothalamus (PVH) in the feeding behavior in mice. Our results indicated that the PVH dopaminergic neurons were critical for extending the food consumption phase and involved in the development of obesity through epigenetic mechanisms. These neurons synchronized with proopiomelanocortin neurons during consumption, were stimulated by proopiomelanocortin activation, and projected to the lateral habenula (LHb), where dopamine receptor D2 was involved in the increase in food consumption. In addition, upregulated tyrosine hydroxylase (TH) expression in PVH was associated with obesity and indispensable for obesity induction in mice lacking Dnmt3a. Taken together, our results highlight the roles of PVH dopaminergic neurons in promoting food consumption and obesity induction.", "classifications": [ { "id": "JPMJCR1921", "label": "JPMJCR1921", "researcher": "Itaru Imayoshi", "type": "grant" }, { "id": "Imayoshi", "label": "Group Imayoshi", "parent": "Imayoshi", "type": "group" }, { "id": "Imayoshi", "label": "Team Imayoshi", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Winda", "last_name": "Ariyani", "name": null }, { "creator_type": "author", "first_name": "Chiharu", "last_name": "Yoshikawa", "name": null }, { "creator_type": "author", "first_name": "Haruka", "last_name": "Tsuneoka", "name": null }, { "creator_type": "author", "first_name": "Izuki", "last_name": "Amano", "name": null }, { "creator_type": "author", "first_name": "Itaru", "last_name": "Imayoshi", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Ichinose", "name": null }, { "creator_type": "author", "first_name": "Chiho", "last_name": "Sumi-Ichinose", "name": null }, { "creator_type": "author", "first_name": "Noriyuki", "last_name": "Koibuchi", "name": null }, { "creator_type": "author", "first_name": "Tadahiro", "last_name": "Kitamura", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Kohno", "name": null } ], "identifiers": { "doi": { "normalized": "10.1073/pnas.2411069122" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "40153459" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "DNA (Cytosine-5-)-Methyltransferases", "descriptor_ui": "D004248", "major_topic": false }, { "descriptor": "DNA Methyltransferase 3A", "descriptor_ui": "D000090205", "major_topic": false }, { "descriptor": "Dopaminergic Neurons", "descriptor_ui": "D059290", "major_topic": true }, { "descriptor": "Eating", "descriptor_ui": "D004435", "major_topic": true }, { "descriptor": "Epigenesis, Genetic", "descriptor_ui": "D044127", "major_topic": false }, { "descriptor": "Feeding Behavior", "descriptor_ui": "D005247", "major_topic": true }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Obesity", "descriptor_ui": "D009765", "major_topic": false }, { "descriptor": "Paraventricular Hypothalamic Nucleus", "descriptor_ui": "D010286", "major_topic": true }, { "descriptor": "Pro-Opiomelanocortin", "descriptor_ui": "D011333", "major_topic": false }, { "descriptor": "Receptors, Dopamine D2", "descriptor_ui": "D017448", "major_topic": false }, { "descriptor": "Tyrosine 3-Monooxygenase", "descriptor_ui": "D014446", "major_topic": false } ], "publication": { "conference_name": null, "date": "2025 Apr", "date_precision": "unknown", "issue": "13", "normalized_date": null, "pages": "e2411069122", "proceedings_title": null, "publisher": "", "title": "Proceedings of the National Academy of Sciences of the United States of America", "volume": "122", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Dopaminergic neurons in the paraventricular hypothalamus extend the food consumption phase.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: T follicular helper (Tfh) cell lymphomas, including their most prevalent form, angioimmunoblastic T-cell lymphoma, frequently present with clinical symptoms, such as fever and rash, accompanied by substantial immune cell infiltration within the tumor microenvironment. These features often obscure the distinction between Tfh lymphoma and other autoimmune or inflammatory conditions. Notably, the p.Gly17Val RHOA (G17V) mutation is commonly associated with Tfh lymphomas, including angioimmunoblastic T-cell lymphoma, suggesting that testing for the G17V mutation may serve as a valuable diagnostic tool. However, it remains unclear which patients would benefit the most from G17V mutation testing. METHODS: In this study, we retrospectively reviewed the medical records of 224 patients tested for the G17V mutation as part of routine clinical practice. RESULTS: We detected G17V in 17 patients. Among Tfh lymphoma cases, the sensitivity and specificity of the G17V test were 0.533 and 0.955, respectively. We further explored the association between G17V positivity and the clinical features of patients undergoing testing for the first time (n = 186). The G17V mutation was more frequent in patients presenting with lymphadenopathy in combination with fever or skin rash and elevated soluble interleukin-2 receptor levels (p = 0.002). The median time from G17V test submission to results was 11.6 d shorter than that for pathological diagnosis (p = 0.0009). CONCLUSIONS: Given the noninvasive nature of the G17V test, its rapid administration to appropriate patients is expected to enable faster and more efficient diagnosis of Tfh lymphomas compared with conventional methods.", "classifications": [ { "id": "Nishikii", "label": "Group Nishikii", "parent": "Shintaku", "type": "group" }, { "id": "Shintaku", "label": "Team Shintaku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yuri", "last_name": "Tsuboi", "name": null }, { "creator_type": "author", "first_name": "Keiichiro", "last_name": "Hattori", "name": null }, { "creator_type": "author", "first_name": "Naoki", "last_name": "Kurita", "name": null }, { "creator_type": "author", "first_name": "Yasuhito", "last_name": "Suehara", "name": null }, { "creator_type": "author", "first_name": "Toru", "last_name": "Nanmoku", "name": null }, { "creator_type": "author", "first_name": "Ryota", "last_name": "Matsuoka", "name": null }, { "creator_type": "author", "first_name": "Ryota", "last_name": "Ishii", "name": null }, { "creator_type": "author", "first_name": "Sakurako", "last_name": "Suma", "name": null }, { "creator_type": "author", "first_name": "Kenichi", "last_name": "Makishima", "name": null }, { "creator_type": "author", "first_name": "Yumiko", "last_name": "Maruyama", "name": null }, { "creator_type": "author", "first_name": "Tatsuhiro", "last_name": "Sakamoto", "name": null }, { "creator_type": "author", "first_name": "Takayasu", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Hidekazu", "last_name": "Nishikii", "name": null }, { "creator_type": "author", "first_name": "Naoshi", "last_name": "Obara", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Matsubara", "name": null }, { "creator_type": "author", "first_name": "Mamiko", "last_name": "Sakata-Yanagimoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/cam4.70955" }, "pmcid": { "normalized": "PMC12065079" }, "pmid": { "normalized": "40347078" } }, "mesh": [ { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Aged, 80 and over", "descriptor_ui": "D000369", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Lymphoma, Follicular", "descriptor_ui": "D008224", "major_topic": true }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": true }, { "descriptor": "Retrospective Studies", "descriptor_ui": "D012189", "major_topic": false }, { "descriptor": "rhoA GTP-Binding Protein", "descriptor_ui": "D020742", "major_topic": true }, { "descriptor": "T-Lymphocytes, Helper-Inducer", "descriptor_ui": "D006377", "major_topic": false } ], "publication": { "conference_name": null, "date": "2025 May", "date_precision": "unknown", "issue": "9", "normalized_date": null, "pages": "e70955", "proceedings_title": null, "publisher": "", "title": "Cancer medicine", "volume": "14", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Real-World Data on the p.Gly17Val RHOA Mutation in Diagnosing T Follicular Helper Cell Lymphomas.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The endoplasmic reticulum (ER) plays crucial roles in maintaining protein quality control and regulating dynamic Ca(2+) storage in eukaryotic cells. However, the proteostasis system involved in ER-mediated protein quality control has not been fully characterized. Here we show that Ca(2+) triggers the condensation of PDIA6, an ER-resident disulfide isomerase and molecular chaperone, into quality control granules. In contrast to the condensation mechanism observed for proteins containing low-complexity domains, our results indicate that transient but specific electrostatic interactions occur between the first and the third folded thioredoxin-like domains of PDIA6. We further show that the PDIA6 condensates recruit proinsulin, thereby accelerating the oxidative proinsulin folding and suppressing the proinsulin aggregation inside quality control granules, essential for secretion of insulin.", "classifications": [ { "id": "Nakabayashi", "label": "Group Nakabayashi", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Young-Ho", "last_name": "Lee", "name": null }, { "creator_type": "author", "first_name": "Tomohide", "last_name": "Saio", "name": null }, { "creator_type": "author", "first_name": "Mai", "last_name": "Watabe", "name": null }, { "creator_type": "author", "first_name": "Motonori", "last_name": "Matsusaki", "name": null }, { "creator_type": "author", "first_name": "Shingo", "last_name": "Kanemura", "name": null }, { "creator_type": "author", "first_name": "Yuxi", "last_name": "Lin", "name": null }, { "creator_type": "author", "first_name": "Taro", "last_name": "Mannen", "name": null }, { "creator_type": "author", "first_name": "Tsubura", "last_name": "Kuramochi", "name": null }, { "creator_type": "author", "first_name": "Yuka", "last_name": "Kamada", "name": null }, { "creator_type": "author", "first_name": "Katsuya", "last_name": "Iuchi", "name": null }, { "creator_type": "author", "first_name": "Michiko", "last_name": "Tajiri", "name": null }, { "creator_type": "author", "first_name": "Kotono", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Yan", "last_name": "Li", "name": null }, { "creator_type": "author", "first_name": "Yunseok", "last_name": "Heo", "name": null }, { "creator_type": "author", "first_name": "Kotone", "last_name": "Ishii", "name": null }, { "creator_type": "author", "first_name": "Kenta", "last_name": "Arai", "name": null }, { "creator_type": "author", "first_name": "Kazunori", "last_name": "Ban", "name": null }, { "creator_type": "author", "first_name": "Mayuko", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Shuichiro", "last_name": "Oshita", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Ninagawa", "name": null }, { "creator_type": "author", "first_name": "Yoshikazu", "last_name": "Hattori", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Kumeta", "name": null }, { "creator_type": "author", "first_name": "Airu", "last_name": "Takeuchi", "name": null }, { "creator_type": "author", "first_name": "Shinji", "last_name": "Kajimoto", "name": null }, { "creator_type": "author", "first_name": "Hiroya", "last_name": "Abe", "name": null }, { "creator_type": "author", "first_name": "Eiichiro", "last_name": "Mori", "name": null }, { "creator_type": "author", "first_name": "Takahiro", "last_name": "Muraoka", "name": null }, { "creator_type": "author", "first_name": "Takakazu", "last_name": "Nakabayashi", "name": null }, { "creator_type": "author", "first_name": "Satoko", "last_name": "Akashi", "name": null }, { "creator_type": "author", "first_name": "Tsukasa", "last_name": "Okiyoneda", "name": null }, { "creator_type": "author", "first_name": "Michele", "last_name": "Vendruscolo", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Inaba", "name": null }, { "creator_type": "author", "first_name": "Masaki", "last_name": "Okumura", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41556-025-01794-8" }, "pmcid": { "normalized": "PMC12611771" }, "pmid": { "normalized": "41219432" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Calcium", "descriptor_ui": "D002118", "major_topic": true }, { "descriptor": "Endoplasmic Reticulum", "descriptor_ui": "D004721", "major_topic": false }, { "descriptor": "HEK293 Cells", "descriptor_ui": "D057809", "major_topic": false }, { "descriptor": "HeLa Cells", "descriptor_ui": "D006367", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Insulin", "descriptor_ui": "D007328", "major_topic": false }, { "descriptor": "Oxidation-Reduction", "descriptor_ui": "D010084", "major_topic": false }, { "descriptor": "Procollagen-Proline Dioxygenase", "descriptor_ui": "D011393", "major_topic": true }, { "descriptor": "Proinsulin", "descriptor_ui": "D011384", "major_topic": true }, { "descriptor": "Protein Disulfide-Isomerases", "descriptor_ui": "D019704", "major_topic": true }, { "descriptor": "Protein Folding", "descriptor_ui": "D017510", "major_topic": true }, { "descriptor": "Proteostasis", "descriptor_ui": "D000074702", "major_topic": false } ], "publication": { "conference_name": null, "date": "2025 Nov", "date_precision": "unknown", "issue": "11", "normalized_date": null, "pages": "1952-1964", "proceedings_title": null, "publisher": "", "title": "Nature cell biology", "volume": "27", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Ca(2+)-driven PDIA6 biomolecular condensation ensures proinsulin folding.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The leaf apex, the distal end of the leaf blade, exhibits enormous variation in shapes across plant species. Among these diverse morphologies, the sharp apex, characterized by its pointed and elongated tip, is important for both species identification and environmental adaptation. Despite its taxonomic and ecological importance, the developmental mechanisms underlying the formation of a sharp apex remain unknown. The present study aims to investigate the curvature patterns and morphogenesis of the sharp apex to uncover these mechanisms using Triadica sebifera leaves. We revealed that the sharp apex marks the maximum positive curvature and is flanked by concave joints with negative curvatures, indicating anisotropic tissue growth and spatially regulated cellular behavior. To investigate the underlying cellular mechanism, we observed cell shapes and cell divisions across different developmental stages and regions. Unlike plant roots or stems, we did not observe highly elongated or aligned cell shapes at the mature stage. Also, unlike serration leaf margins, we did not observe increased cell proliferation near the sharply elongated apex. Instead, we identified a biregional differentiation in cell division angles, and our simulations confirmed that these division angles could generate the sharply elongated apex that might be influenced by anisotropic cell growth. Then, further generalizations were made from this case study of T. sebifera, revealing that spatiotemporal change in cell division angle is essential to make sharp-tipped leaf shape.", "classifications": [ { "id": "Mochizuki", "label": "Group Mochizuki", "parent": "Eiraku", "type": "group" }, { "id": "Eiraku", "label": "Team Eiraku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Zining", "last_name": "Wang", "name": null }, { "creator_type": "author", "first_name": "Yasuhiro", "last_name": "Inoue", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Mochizuki", "name": null }, { "creator_type": "author", "first_name": "Hirokazu", "last_name": "Tsukaya", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/tpj.70310" }, "pmcid": { "normalized": "PMC12228550" }, "pmid": { "normalized": "40616818" } }, "mesh": [ { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Cell Division", "descriptor_ui": "D002455", "major_topic": false }, { "descriptor": "Cell Proliferation", "descriptor_ui": "D049109", "major_topic": false }, { "descriptor": "Cell Shape", "descriptor_ui": "D048430", "major_topic": false }, { "descriptor": "Plant Leaves", "descriptor_ui": "D018515", "major_topic": true } ], "publication": { "conference_name": null, "date": "2025 Jul", "date_precision": "unknown", "issue": "1", "normalized_date": null, "pages": "e70310", "proceedings_title": null, "publisher": "", "title": "The Plant journal : for cell and molecular biology", "volume": "123", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Biregionally differentiated growth generates sharp apex and concave joints in leaves.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Sulfur, like oxygen, belongs to Group 16 of the periodic table and is characterized by its flexibility in both donating and accepting electrons, as well as its wide range of oxidation states. These properties enable sulfur to participate in diverse redox reactions. In biological systems, sulfur plays vital roles as a component of catalytic centers of enzymes and as a redox sensor. Moreover, sulfur is the only element known to form stable linear chains through homoelemental bonding, a phenomenon known as catenation, resulting in a variety of allotropes present widely in nature. Advances in analytical techniques have recently revealed the endogenous presence of\"supersulfides\", which contain sulfur catenation structures. The physiological and pathological functions of these species are gradually being elucidated. This review focuses on the chemical properties and biological functions of supersulfides, with particular emphasis on their roles in cancer. Furthermore, we discuss the therapeutic potential of targeting the\"over-reduced state,\"a redox imbalance caused by excessive production of supersulfides.", "classifications": [ { "id": "Akaike", "label": "Group Akaike", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Keito", "last_name": "Okazaki", "name": null }, { "creator_type": "author", "first_name": "Takaaki", "last_name": "Akaike", "name": null }, { "creator_type": "author", "first_name": "Hozumi", "last_name": "Motohashi", "name": null } ], "identifiers": { "doi": { "normalized": null }, "pmcid": { "normalized": null }, "pmid": { "normalized": "40840901" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Neoplasms", "descriptor_ui": "D009369", "major_topic": true }, { "descriptor": "Oxidation-Reduction", "descriptor_ui": "D010084", "major_topic": false }, { "descriptor": "Sulfur", "descriptor_ui": "D013455", "major_topic": true } ], "publication": { "conference_name": null, "date": "2025 Aug", "date_precision": "unknown", "issue": "8", "normalized_date": null, "pages": "541-548", "proceedings_title": null, "publisher": "", "title": "Gan to kagaku ryoho. Cancer & chemotherapy", "volume": "52", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "[Sulfur Metabolism in Cancer Malignancy and Its Potential for Therapeutic Application].", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Retroperitoneal sarcoma (RPS) is a biologically heterogeneous tumor and rare malignant mesenchymal soft-tissue neoplasm. Although the 5-year overall survival rate for RPS is approximately 60%-70%, it is quite low for unresectable tumors. Surgery is a standard treatment for RPS. Immune checkpoint inhibitors (ICIs) have shown promising effects against various tumor types; however, the efficacy of ICIs for RPS is unclear and the combination of ICIs with other drugs or treatments has been considered. We report the case of a 71-year-old woman with dual primary cancer, retroperitoneal leiomyosarcoma, and malignant melanoma in the lower leg. Retroperitoneal leiomyosarcoma was considered inoperable and managed with palliative radiotherapy. However, subsequent treatment with nivolumab for melanoma resulted in significant shrinkage of the retroperitoneal leiomyosarcoma. The genomic analysis revealed a low TMB and poor CD8 score. These findings suggest that the retroperitoneal leiomyosarcoma would be immunologically cold. We report an unexpectedly successful treatment of RPS with ICI therapy after radiotherapy. There have been few reports on the detailed genetic profiles of sarcomas that respond to ICI therapy. Our findings suggest that the combination of radiotherapy and ICIs has therapeutic potential for immunologically cold tumors and may be a useful treatment strategy for RPS. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13691-025-00771-0.", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Shin", "last_name": "Ishihara", "name": null }, { "creator_type": "author", "first_name": "Kouya", "last_name": "Shiraishi", "name": null }, { "creator_type": "author", "first_name": "Akihiko", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Taisuke", "last_name": "Mori", "name": null }, { "creator_type": "author", "first_name": "Toshihide", "last_name": "Ueno", "name": null }, { "creator_type": "author", "first_name": "Hanako", "last_name": "Ono", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Ichikawa", "name": null }, { "creator_type": "author", "first_name": "Shigehiro", "last_name": "Yagishita", "name": null }, { "creator_type": "author", "first_name": "Shinji", "last_name": "Kohsaka", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Goto", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null }, { "creator_type": "author", "first_name": "Akinobu", "last_name": "Hamada", "name": null }, { "creator_type": "author", "first_name": "Akira", "last_name": "Kawai", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Mano", "name": null }, { "creator_type": "author", "first_name": "Shintaro", "last_name": "Iwata", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/s13691-025-00771-0" }, "pmcid": { "normalized": "PMC12226442" }, "pmid": { "normalized": "40620529" } }, "mesh": [], "publication": { "conference_name": null, "date": "2025 Jul", "date_precision": "unknown", "issue": "3", "normalized_date": null, "pages": "190-197", "proceedings_title": null, "publisher": "", "title": "International cancer conference journal", "volume": "14", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Favorable response to nivolumab combined with radiotherapy for retroperitoneal leiomyosarcoma.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: Cancer cells reprogram their metabolism to sustain energy production and biosynthesis for malignant proliferation; however, their metabolic phenotypes vary significantly across different growth environments, creating discrepancies between in vitro and in vivo findings. These inconsistencies pose challenges for translating metabolic research into clinical applications. The emergence of 3D culture models as in vitro systems that accurately mimic the in vivo environment can mitigate these challenges by providing conditions that reflect physiological architecture and metabolic interactions. Therefore, we investigated the impact of the purine metabolism enzyme hypoxanthine-guanine phosphoribosyltransferase 1 (HPRT1) on the proliferation and metabolism of SCLC cells using 2D and 3D culture models, with the goal of identifying context-specific metabolic regulation not captured in conventional 2D cultures. METHODS: We evaluated cell proliferation and performed metabolomic profiling of HPRT1-knockout (KO) SCLC cells grown in 2D cultures, two 3D culture systems, and mouse xenograft models. Metabolomic profiling was performed using CE-TOFMS, followed by PCA and pathway analysis. The expression of beta-alanine (beta-Ala) metabolism-related genes, including carnosine synthase 1 (CARNS1), was assessed by RNA-seq and RT-PCR. CARNS1 expression was further evaluated in publicly available lung cancer datasets, including both cell line and clinical tumor cohorts, to determine its association with patient prognosis and its correlation with HPRT1 expression. RESULTS: The knockout of HPRT1 significantly reduced cell proliferation in 3D cultures and in vivo but had a minimal impact in 2D cultures. Comprehensive metabolomic analyses of HPRT1-KO cells revealed extensive alterations in amino acid and purine metabolism both in vitro and in vivo. Notably, the effect of HPRT1 KO on beta-Ala metabolism differed between 2D and 3D cultures. In 3D cultures, HPRT1 KO led to increased expression of the endogenous antitumor metabolite carnosine and its biosynthetic enzyme CARNS1 within the beta-Ala metabolic pathway. Furthermore, analysis of clinical databases showed that high CARNS1 expression correlated with improved prognosis in patients with lung cancer and negatively correlated with HPRT1 expression in tumor tissues. CONCLUSION: This study highlights the potential of 3D culture systems to elucidate context-specific mechanisms of metabolic regulation, such as the suppressive effect of HPRT1 on carnosine production. Our findings demonstrate that metabolic phenotypes observed in 2D cultures may not fully capture the complexity of in vivo metabolism, whereas 3D models can reveal regulatory pathways that are otherwise overlooked, including context-dependent regulation of carnosine metabolism by HPRT1.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Sho", "last_name": "Tabata", "name": null }, { "creator_type": "author", "first_name": "Ichiro", "last_name": "Fujimoto", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Hideki", "last_name": "Makinoshima", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/cam4.71452" }, "pmcid": { "normalized": "PMC12688478" }, "pmid": { "normalized": "41365579" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Culture Techniques", "descriptor_ui": "D018929", "major_topic": true }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Cell Proliferation", "descriptor_ui": "D049109", "major_topic": false }, { "descriptor": "Gene Knockout Techniques", "descriptor_ui": "D055786", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Hypoxanthine Phosphoribosyltransferase", "descriptor_ui": "D007041", "major_topic": true }, { "descriptor": "Lung Neoplasms", "descriptor_ui": "D008175", "major_topic": true }, { "descriptor": "Metabolomics", "descriptor_ui": "D055432", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Small Cell Lung Carcinoma", "descriptor_ui": "D055752", "major_topic": true } ], "publication": { "conference_name": null, "date": "2025 Dec", "date_precision": "unknown", "issue": "23", "normalized_date": null, "pages": "e71452", "proceedings_title": null, "publisher": "", "title": "Cancer medicine", "volume": "14", "year": 2025 }, "ssbd": { "database": [], "repository": [] }, "title": "Context-Specific Metabolic Alterations in HPRT1 Knockout Cells Within a 3D Culture System.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Alpha-1-antitrypsin (AAT), a circulating serine protease inhibitor, is an acute inflammatory response protein with anti-inflammatory functions. The C-terminal peptides of AAT are found in various tissues and have been proposed as putative bioactive peptides with multiple functions, but its mechanism of action remains unclear. We previously reported that a mouse AAT C-terminal peptide of 35 amino acids (mAAT-C(1-35)) penetrates plasma membrane and associates guanine nucleotide-binding protein subunit alpha 13 (Galpha13). Here, we show that mAAT-C(1-35) binds directly to the guanosine diphosphate (GDP)-bound form of Galpha13 through the N-terminal region (mAAT-C(1-17)), thereby facilitating the interaction of Galpha13・GDP with its effector proteins. The minimal sequence (mAAT-C(3-16)) and essential amino acid residue (Phe11) of mAAT-C(1-17) were identified as being necessary for this effect. A molecular dynamics simulation for the Galpha13・GDP-mAAT-C(1-17) complex model showed that binding of mAAT-C(1-17) to the region surrounded by switch regions of Galpha13 stabilizes the flexible switch II and III regions, thereby maintaining their active conformation. In addition, mAAT-C(1-35) activates the Galpha13 signalling pathway in cells where Phe11 is required. Our study reveals the structure-based mechanism of action of AAT-C peptides in the regulation of Galpha13, and demonstrates that AAT-C peptides represent a biological peptide capable of activating G protein signals in a manner that is independent of G-protein-coupled receptors.", "classifications": [ { "id": "Toyoshima", "label": "Group Toyoshima", "parent": "Toyoshima", "type": "group" }, { "id": "Toyoshima", "label": "Team Toyoshima", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yonghak", "last_name": "Park", "name": null }, { "creator_type": "author", "first_name": "Shigeyuki", "last_name": "Matsumoto", "name": null }, { "creator_type": "author", "first_name": "Kosuke", "last_name": "Ogata", "name": null }, { "creator_type": "author", "first_name": "Biao", "last_name": "Ma", "name": null }, { "creator_type": "author", "first_name": "Ryo", "last_name": "Kanada", "name": null }, { "creator_type": "author", "first_name": "Yuta", "last_name": "Isaka", "name": null }, { "creator_type": "author", "first_name": "Norihito", "last_name": "Arichi", "name": null }, { "creator_type": "author", "first_name": "Xiaowen", "last_name": "Liang", "name": null }, { "creator_type": "author", "first_name": "Ritsuko", "last_name": "Maki", "name": null }, { "creator_type": "author", "first_name": "Tohru", "last_name": "Kozasa", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Okuno", "name": null }, { "creator_type": "author", "first_name": "Hiroaki", "last_name": "Ohno", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Ishihama", "name": null }, { "creator_type": "author", "first_name": "Fumiko", "last_name": "Toyoshima", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.jbc.2024.108136" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "39730062" } }, "mesh": [ { "descriptor": "alpha 1-Antitrypsin", "descriptor_ui": "D000515", "major_topic": true }, { "descriptor": "Amino Acid Sequence", "descriptor_ui": "D000595", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "GTP-Binding Protein alpha Subunits, G12-G13", "descriptor_ui": "D044365", "major_topic": true }, { "descriptor": "HEK293 Cells", "descriptor_ui": "D057809", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Molecular Dynamics Simulation", "descriptor_ui": "D056004", "major_topic": false }, { "descriptor": "Peptide Fragments", "descriptor_ui": "D010446", "major_topic": true }, { "descriptor": "Peptides", "descriptor_ui": "D010455", "major_topic": true }, { "descriptor": "Protein Binding", "descriptor_ui": "D011485", "major_topic": false } ], "publication": { "conference_name": null, "date": "2024 Dec 25", "date_precision": "day", "issue": "", "normalized_date": "2024-12-25", "pages": "108136", "proceedings_title": null, "publisher": "", "title": "The Journal of biological chemistry", "volume": "", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Receptor-independent regulation of Galpha13 by alpha-1-antitrypsin C-terminal peptides.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "KRAS(G12C) inhibitors sotorasib and adagrasib have been approved for the treatment of KRAS(G12C)-mutant non-small cell lung cancer (NSCLC). However, the efficacy of single-agent treatments is limited, presumably due to multiple resistance mechanisms. To overcome these therapeutic limitations, combination strategies that potentiate the antitumor efficacy of KRAS(G12C) inhibitors must be developed. Through unbiased high-throughput screening of 1395 kinase inhibitors, we identified adavosertib, a WEE1 inhibitor, as a promising combination partner of sotorasib. The combination of sotorasib and adavosertib exhibited synergistic antiproliferative activities both in vitro and in vivo, irrespective of TP53, STK11, and KEAP1 co-mutation profiles. WEE1 inhibition potentiated MCL-1-mediated apoptosis in sotorasib-treated cancer cells. Mechanistically, the combination downregulated MCL-1 protein levels by attenuating de novo translation and enhancing its degradation. WEE1 overexpression conferred resistance against sotorasib via MCL-1 upregulation. Moreover, cells that acquired sotorasib resistance profoundly upregulated both WEE1 and MCL-1 proteins, highlighting WEE1 as a crucial driver of sotorasib resistance. Importantly, WEE1 inhibition re-sensitized resistant cells to sotorasib treatment. The current findings demonstrate that combined inhibition of KRAS(G12C) and WEE1 not only exhibits synergistic antitumor efficacy but also overcomes resistance to KRAS(G12C) inhibitors, thus representing a novel therapeutic strategy for KRAS(G12C)-mutant NSCLC.", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Gaku", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Kosuke", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Ryo", "last_name": "Kamata", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Tomoko", "last_name": "Yamamori-Morita", "name": null }, { "creator_type": "author", "first_name": "Takehiro", "last_name": "Nakao", "name": null }, { "creator_type": "author", "first_name": "Jie", "last_name": "Liu", "name": null }, { "creator_type": "author", "first_name": "Shunta", "last_name": "Mori", "name": null }, { "creator_type": "author", "first_name": "Shigehiro", "last_name": "Yagishita", "name": null }, { "creator_type": "author", "first_name": "Akinobu", "last_name": "Hamada", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Shinno", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Hidehito", "last_name": "Horinouchi", "name": null }, { "creator_type": "author", "first_name": "Yuichiro", "last_name": "Ohe", "name": null }, { "creator_type": "author", "first_name": "Shun-Ichi", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null }, { "creator_type": "author", "first_name": "Hidenori", "last_name": "Kitai", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Konno", "name": null }, { "creator_type": "author", "first_name": "Susumu S.", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Akihiro", "last_name": "Ohashi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.canlet.2024.217414" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "39725152" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Apoptosis", "descriptor_ui": "D017209", "major_topic": false }, { "descriptor": "Carcinoma, Non-Small-Cell Lung", "descriptor_ui": "D002289", "major_topic": true }, { "descriptor": "Cell Cycle Proteins", "descriptor_ui": "D018797", "major_topic": true }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Cell Proliferation", "descriptor_ui": "D049109", "major_topic": false }, { "descriptor": "Drug Resistance, Neoplasm", "descriptor_ui": "D019008", "major_topic": true }, { "descriptor": "Drug Synergism", "descriptor_ui": "D004357", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Lung Neoplasms", "descriptor_ui": "D008175", "major_topic": true }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": false }, { "descriptor": "Myeloid Cell Leukemia Sequence 1 Protein", "descriptor_ui": "D064549", "major_topic": false }, { "descriptor": "Nuclear Proteins", "descriptor_ui": "D009687", "major_topic": false }, { "descriptor": "Protein Kinase Inhibitors", "descriptor_ui": "D047428", "major_topic": true }, { "descriptor": "Protein-Tyrosine Kinases", "descriptor_ui": "D011505", "major_topic": true }, { "descriptor": "Proto-Oncogene Proteins p21(ras)", "descriptor_ui": "D016283", "major_topic": true }, { "descriptor": "Pyrazoles", "descriptor_ui": "D011720", "major_topic": false }, { "descriptor": "Pyrimidines", "descriptor_ui": "D011743", "major_topic": false }, { "descriptor": "Pyrimidinones", "descriptor_ui": "D011744", "major_topic": false }, { "descriptor": "Xenograft Model Antitumor Assays", "descriptor_ui": "D023041", "major_topic": false } ], "publication": { "conference_name": null, "date": "2024 Dec 24", "date_precision": "day", "issue": "", "normalized_date": "2024-12-24", "pages": "217414", "proceedings_title": null, "publisher": "", "title": "Cancer letters", "volume": "611", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "WEE1 confers resistance to KRAS(G12C) inhibitors in non-small cell lung cancer.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The question of how changes in chemoattractant concentration translate into the chemotactic response of immune cells serves as a paradigm for the quantitative understanding of how cells perceive and process temporal and spatial information. Here, using a microfluidic approach, we analyzed the migration of neutrophil-like HL-60 cells to a traveling wave of the chemoattractants fMLP and leukotriene B4 (LTB4). We found that under a pulsatile wave that travels at a speed of 95 and 170 microm/min, cells move forward in the front of the wave but slow down and randomly orient at the back due to temporal decrease in the attractant concentration. Under a slower wave, cells re-orient and migrate at the back of the wave; thus, cell displacement is canceled out or even becomes negative as cells chase the receding wave. FRET-based analysis indicated that these patterns of movement correlated well with spatiotemporal changes in Cdc42 activity. Furthermore, pharmacological perturbations showed that (re-)orientation in front and back of the wave had different susceptibility to Cdc42 and ROCK inhibition. These results suggest that pulsatile attractant waves may recruit or disperse neutrophils, depending on their speed and degree of cell polarization.", "classifications": [ { "id": "JPMJCR1923", "label": "JPMJCR1923", "researcher": "Satoshi Sawai", "type": "grant" }, { "id": "Sawai", "label": "Group Sawai", "parent": "Sawai", "type": "group" }, { "id": "Sawai", "label": "Team Sawai", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Motohiko", "last_name": "Ishida", "name": null }, { "creator_type": "author", "first_name": "Masahito", "last_name": "Uwamichi", "name": null }, { "creator_type": "author", "first_name": "Akihiko", "last_name": "Nakajima", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Sawai", "name": null } ], "identifiers": { "doi": { "normalized": "10.1091/mbc.e24-06-0245" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "39718770" } }, "mesh": [ { "descriptor": "cdc42 GTP-Binding Protein", "descriptor_ui": "D020764", "major_topic": false }, { "descriptor": "Cell Movement", "descriptor_ui": "D002465", "major_topic": false }, { "descriptor": "Chemotactic Factors", "descriptor_ui": "D002630", "major_topic": false }, { "descriptor": "Chemotaxis", "descriptor_ui": "D002633", "major_topic": true }, { "descriptor": "Fluorescence Resonance Energy Transfer", "descriptor_ui": "D031541", "major_topic": false }, { "descriptor": "HL-60 Cells", "descriptor_ui": "D018922", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Leukotriene B4", "descriptor_ui": "D007975", "major_topic": false }, { "descriptor": "N-Formylmethionine Leucyl-Phenylalanine", "descriptor_ui": "D009240", "major_topic": false }, { "descriptor": "Neutrophils", "descriptor_ui": "D009504", "major_topic": true } ], "publication": { "conference_name": null, "date": "2024 Dec 24", "date_precision": "day", "issue": "", "normalized_date": "2024-12-24", "pages": "mbcE24060245", "proceedings_title": null, "publisher": "", "title": "Molecular biology of the cell", "volume": "", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Traveling wave chemotaxis of neutrophil-like HL-60 cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Background: Chemoresistance is an important issue to be solved in breast cancer. It is well known that the content and morphology of collagens in tumor tissues are drastically altered following chemotherapy, and discoidin domain receptor 2 (DDR2) is a unique type of receptor tyrosine kinase (RTK). This RTK is activated by collagens, playing important roles in human malignancies. However, the contribution to the chemoresistance of DDR2 in terms of the association with collagens remains largely unclear in breast cancer. Methods: We immunolocalized DDR2 and collagen type I in 224 breast cancer tissues and subsequently conducted in vitro studies to confirm the role of DDR2 in breast cancer chemoresistance using chemosensitive and chemoresistant cell lines. Results: DDR2 immunoreactivity was positively correlated with aggressive behaviors of breast cancer and was significantly associated with an increased risk of recurrence, especially in those who received chemotherapy. Moreover, in vitro experiments demonstrated that DDR2 promoted the proliferative activity of breast cancer cells, and cell viability after epirubicin treatment was significantly maintained by DDR2 in a collagen I-dependent manner. Conclusions: These data suggested that DDR2 could be a poor prognostic factor associated with cell proliferation and chemotherapy resistance in human breast cancer.", "classifications": [ { "id": "Suzuki", "label": "Group Suzuki", "parent": "Takekawa", "type": "group" }, { "id": "Takekawa", "label": "Team Takekawa", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Ai", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Kiyoshi", "last_name": "Takagi", "name": null }, { "creator_type": "author", "first_name": "Momoka", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Mio", "last_name": "Yamaguchi-Tanaka", "name": null }, { "creator_type": "author", "first_name": "Mikoto", "last_name": "Sagehashi", "name": null }, { "creator_type": "author", "first_name": "Yasuhiro", "last_name": "Miki", "name": null }, { "creator_type": "author", "first_name": "Minoru", "last_name": "Miyashita", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Suzuki", "name": null } ], "identifiers": { "doi": { "normalized": "10.3390/cancers16244285" }, "pmcid": { "normalized": "PMC11674238" }, "pmid": { "normalized": "39766183" } }, "mesh": [], "publication": { "conference_name": null, "date": "2024 Dec 23", "date_precision": "day", "issue": "24", "normalized_date": "2024-12-23", "pages": "", "proceedings_title": null, "publisher": "", "title": "Cancers", "volume": "16", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Discoidin Domain Receptor 2 Contributes to Breast Cancer Progression and Chemoresistance by Interacting with Collagen Type I.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "", "classifications": [ { "id": "Fujita", "label": "Group Fujita", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Karen", "last_name": "Faulds", "name": null }, { "creator_type": "author", "first_name": "Katsumasa", "last_name": "Fujita", "name": null }, { "creator_type": "author", "first_name": "Pavel", "last_name": "Matousek", "name": null }, { "creator_type": "author", "first_name": "Zachary D.", "last_name": "Schultz", "name": null } ], "identifiers": { "doi": { "normalized": "10.1039/d4an90097a" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "39688143" } }, "mesh": [], "publication": { "conference_name": null, "date": "2024 Dec 17", "date_precision": "day", "issue": "", "normalized_date": "2024-12-17", "pages": "", "proceedings_title": null, "publisher": "", "title": "The Analyst", "volume": "", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "150 years of Analyst encompassing Raman and SERS development.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Messenger RNA vaccines based on lipid nanoparticles (mRNA-LNPs) are promising vaccine modalities. However, mRNA-LNP vaccines frequently cause adverse reactions such as swelling and fever in humans, partly due to the inflammatory nature of LNP. Modification of the ionizable lipids used in LNP is one approach to avoid these adverse reactions. Herein, we report the development of mRNA-LNP vaccines with better protective immunity and reduced adverse reactions using LNP, which contains a disulfide (SS)-cleavable bond and pH-activated lipid-like materials with oleic acid (ssPalmO) as an ionizable lipid (LNP(ssPalmO)). We used mRNA expressing H5N1 subtype high-pathogenicity avian influenza virus-derived hemagglutinin or neuraminidase to generate mRNA-LNP vaccines against H5N1 influenza. Compared with conventional LNP, mRNA-LNP(ssPalmO) induced comparable antigen-specific antibodies and better interferon-gamma (IFN-gamma)-producing T-helper type-1 (Th1) responses in mice. Both mRNA-LNP(ssPalmO) and conventional mRNA-LNP conferred strong protection against homologous H5N1 virus challenge. In addition, mRNA-LNP(ssPalmO) showed better cross-protection against heterologous H5N1 virus challenge compared with conventional mRNA-LNPs. Furthermore, we observed that mRNA-LNP(ssPalmO) induced less inflammatory responses (e.g., inflammatory cytokine production and vascular hyperpermeability) and fewer adverse reactions (e.g., weight loss and fever) compared with conventional mRNA-LNP. These results suggest that mRNA-LNP(ssPalmO) would be a safe alternative to conventional vaccines to overcome mRNA-LNP vaccine hesitancy.", "classifications": [ { "id": "Yamamoto", "label": "Group Yamamoto", "parent": "Toyoshima", "type": "group" }, { "id": "Toyoshima", "label": "Team Toyoshima", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Atsushi", "last_name": "Kawai", "name": null }, { "creator_type": "author", "first_name": "Taro", "last_name": "Shimizu", "name": null }, { "creator_type": "author", "first_name": "Hiroki", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Shintaro", "last_name": "Shichinohe", "name": null }, { "creator_type": "author", "first_name": "Jessica", "last_name": "Anindita", "name": null }, { "creator_type": "author", "first_name": "Mika", "last_name": "Hirose", "name": null }, { "creator_type": "author", "first_name": "Eigo", "last_name": "Kawahara", "name": null }, { "creator_type": "author", "first_name": "Kota", "last_name": "Senpuku", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Shimooka", "name": null }, { "creator_type": "author", "first_name": "Le Thi", "last_name": "Quynh Mai", "name": null }, { "creator_type": "author", "first_name": "Ryo", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Takuto", "last_name": "Nogimori", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Toshiro", "last_name": "Hirai", "name": null }, { "creator_type": "author", "first_name": "Takayuki", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Tokiko", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Hidetaka", "last_name": "Akita", "name": null }, { "creator_type": "author", "first_name": "Yasuo", "last_name": "Yoshioka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.ymthe.2024.12.032" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "39690742" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Antibodies, Viral", "descriptor_ui": "D000914", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Influenza A Virus, H5N1 Subtype", "descriptor_ui": "D053124", "major_topic": true }, { "descriptor": "Influenza Vaccines", "descriptor_ui": "D007252", "major_topic": true }, { "descriptor": "Influenza, Human", "descriptor_ui": "D007251", "major_topic": false }, { "descriptor": "Interferon-gamma", "descriptor_ui": "D007371", "major_topic": false }, { "descriptor": "Lipids", "descriptor_ui": "D008055", "major_topic": true }, { "descriptor": "Liposomes", "descriptor_ui": "D008081", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred BALB C", "descriptor_ui": "D008807", "major_topic": false }, { "descriptor": "mRNA Vaccines", "descriptor_ui": "D000087503", "major_topic": true }, { "descriptor": "Nanoparticles", "descriptor_ui": "D053758", "major_topic": true }, { "descriptor": "Orthomyxoviridae Infections", "descriptor_ui": "D009976", "major_topic": true }, { "descriptor": "RNA, Messenger", "descriptor_ui": "D012333", "major_topic": true } ], "publication": { "conference_name": null, "date": "2024 Dec 17", "date_precision": "day", "issue": "", "normalized_date": "2024-12-17", "pages": "S1525-0016(24)00831-1", "proceedings_title": null, "publisher": "", "title": "Molecular therapy : the journal of the American Society of Gene Therapy", "volume": "", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Low-inflammatory lipid nanoparticle-based mRNA vaccine elicits protective immunity against H5N1 high-pathogenicity avian influenza virus with reduced adverse reactions.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Raman microscopy is an emerging molecular imaging technology, yet its signal-to-noise ratio (SNR) in measurements of biological specimens is severely limited because of the small cross section of Raman scattering. Here, we present Raman imaging techniques of cryofixed specimens to overcome SNR limitations by enabling long exposure of specimens under highly stabilized low-temperature conditions. The observation of frozen specimens in a cryostat at a constant low temperature immediately after rapid freezing enabled the improvement of SNR and enhanced the spatial and spectral resolution. We also confirmed that the cryofixation can preserve physicochemical states of specimens by observing alkyne-labeled coenzyme Q in cytosol and hemeproteins in acute ischemic myocardium, which cannot be done by fixation using chemical reagents. Last, we applied the technique for multiplex Raman imaging of label-free endogenous molecules and alkyne-tagged molecules in cryofixed HeLa cells, demonstrating its capability of high-content imaging of complex biological phenomena while maintaining physiological conditions.", "classifications": [ { "id": "JPMJCR1925", "label": "JPMJCR1925", "researcher": "Katsumasa Fujita", "type": "grant" }, { "id": "Fujita", "label": "Group Fujita", "parent": "Fujita", "type": "group" }, { "id": "Sodeoka", "label": "Group Sodeoka", "parent": "Fujita", "type": "group" }, { "id": "Tanaka", "label": "Group Tanaka", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Kenta", "last_name": "Mizushima", "name": null }, { "creator_type": "author", "first_name": "Yasuaki", "last_name": "Kumamoto", "name": null }, { "creator_type": "author", "first_name": "Shoko", "last_name": "Tamura", "name": null }, { "creator_type": "author", "first_name": "Masahito", "last_name": "Yamanaka", "name": null }, { "creator_type": "author", "first_name": "Kentaro", "last_name": "Mochizuki", "name": null }, { "creator_type": "author", "first_name": "Menglu", "last_name": "Li", "name": null }, { "creator_type": "author", "first_name": "Syusuke", "last_name": "Egoshi", "name": null }, { "creator_type": "author", "first_name": "Kosuke", "last_name": "Dodo", "name": null }, { "creator_type": "author", "first_name": "Yoshinori", "last_name": "Harada", "name": null }, { "creator_type": "author", "first_name": "Nicholas I.", "last_name": "Smith", "name": null }, { "creator_type": "author", "first_name": "Mikiko", "last_name": "Sodeoka", "name": null }, { "creator_type": "author", "first_name": "Hideo", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Katsumasa", "last_name": "Fujita", "name": null } ], "identifiers": { "doi": { "normalized": "10.1126/sciadv.adn0110" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "39661690" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cryopreservation", "descriptor_ui": "D015925", "major_topic": false }, { "descriptor": "HeLa Cells", "descriptor_ui": "D006367", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Microscopy", "descriptor_ui": "D008853", "major_topic": false }, { "descriptor": "Molecular Imaging", "descriptor_ui": "D057054", "major_topic": false }, { "descriptor": "Myocardium", "descriptor_ui": "D009206", "major_topic": false }, { "descriptor": "Signal-To-Noise Ratio", "descriptor_ui": "D059629", "major_topic": false }, { "descriptor": "Spectrum Analysis, Raman", "descriptor_ui": "D013059", "major_topic": true }, { "descriptor": "Ubiquinone", "descriptor_ui": "D014451", "major_topic": false } ], "publication": { "conference_name": null, "date": "2024 Dec 13", "date_precision": "day", "issue": "50", "normalized_date": "2024-12-13", "pages": "", "proceedings_title": null, "publisher": "", "title": "Science Advances", "volume": "10", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Raman microscopy of cryofixed biological specimens for high-resolution and high-sensitivity chemical imaging.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "During morphogenesis, epithelial sheets undergo sequential folding to form three-dimensional organ structures. The resulting folds are often irreversible, ensuring that morphogenesis progresses in one direction. However, the mechanism establishing folding irreversibility remains unclear. Here, we report a mechanical property of epithelia that determines folding irreversibility. Using a mechanical assay, we demonstrate that long-term, high-curvature folding induces plastic, irreversible deformations, while short-term or low-curvature folding results in an elastic, shape-restoring response. This elastic-plastic transition occurs in a switch-like manner, with critical thresholds in folding curvature and duration. The transition is induced by F-actin accumulating into a bracket-like structure across the fold, triggered by cells sensing deformations via mechanosensitive signaling pathways, including TRPC 3/6-mediated calcium influx and ligand-independent EGFR activation. These results demonstrate that cells control epithelial folding irreversibility by detecting folding characteristics and adaptively switching between elastic and plastic responses, providing mechanical insight into the directionality of morphogenesis.", "classifications": [ { "id": "JPMJCR1921", "label": "JPMJCR1921", "researcher": "Itaru Imayoshi", "type": "grant" }, { "id": "Imayoshi", "label": "Group Imayoshi", "parent": "Imayoshi", "type": "group" }, { "id": "Okuda", "label": "Group Okuda", "parent": "Imayoshi", "type": "group" }, { "id": "Imayoshi", "label": "Team Imayoshi", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Aki", "last_name": "Teranishi", "name": null }, { "creator_type": "author", "first_name": "Misato", "last_name": "Mori", "name": null }, { "creator_type": "author", "first_name": "Rihoko", "last_name": "Ichiki", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Toda", "name": null }, { "creator_type": "author", "first_name": "Go", "last_name": "Shioi", "name": null }, { "creator_type": "author", "first_name": "Satoru", "last_name": "Okuda", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41467-024-54906-7" }, "pmcid": { "normalized": "PMC11638340" }, "pmid": { "normalized": "39668169" } }, "mesh": [ { "descriptor": "Actins", "descriptor_ui": "D000199", "major_topic": true }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Calcium", "descriptor_ui": "D002118", "major_topic": false }, { "descriptor": "Dogs", "descriptor_ui": "D004285", "major_topic": false }, { "descriptor": "Elasticity", "descriptor_ui": "D004548", "major_topic": false }, { "descriptor": "Epithelial Cells", "descriptor_ui": "D004847", "major_topic": true }, { "descriptor": "Epithelium", "descriptor_ui": "D004848", "major_topic": false }, { "descriptor": "ErbB Receptors", "descriptor_ui": "D066246", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Madin Darby Canine Kidney Cells", "descriptor_ui": "D061985", "major_topic": false }, { "descriptor": "Mechanotransduction, Cellular", "descriptor_ui": "D040542", "major_topic": false }, { "descriptor": "Morphogenesis", "descriptor_ui": "D009024", "major_topic": true }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false } ], "publication": { "conference_name": null, "date": "2024 Dec 12", "date_precision": "day", "issue": "1", "normalized_date": "2024-12-12", "pages": "10476", "proceedings_title": null, "publisher": "", "title": "Nature communications", "volume": "15", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "An actin bracket-induced elastoplastic transition determines epithelial folding irreversibility.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The three-vessel view (3VV) is a standardized transverse scanning plane used in fetal cardiac ultrasound screening to measure the absolute and relative diameters of the pulmonary artery (PA), ascending aorta (Ao), and superior vena cava, as required. The PA/Ao ratio is used to support the diagnosis of congenital heart disease (CHD). However, vascular diameters are measured manually by examiners, which causes intra- and interobserver variability in clinical practice. In the present study, we aimed to develop an artificial intelligence-based method for the standardized and quantitative evaluation of 3VV. In total, 315 cases and 20 examiners were included in this study. We used the object-detection software YOLOv7 for the automated extraction of 3VV images and compared three segmentation algorithms: DeepLabv3+, UNet3+, and SegFormer. Using the PA/Ao ratios based on vascular segmentation, YOLOv7 plus UNet3+ yielded the most appropriate classification for normal fetuses and those with CHD. Furthermore, YOLOv7 plus UNet3+ achieved an arithmetic mean value of 0.883 for the area under the receiver operating characteristic curve, which was higher than 0.749 for residents and 0.808 for fellows. Our automated method may support unskilled examiners in performing quantitative and objective assessments of 3VV images during fetal cardiac ultrasound screening.", "classifications": [ { "id": "Hamamoto", "label": "Group Hamamoto", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Rina", "last_name": "Aoyama", "name": null }, { "creator_type": "author", "first_name": "Masaaki", "last_name": "Komatsu", "name": null }, { "creator_type": "author", "first_name": "Naoaki", "last_name": "Harada", "name": null }, { "creator_type": "author", "first_name": "Reina", "last_name": "Komatsu", "name": null }, { "creator_type": "author", "first_name": "Akira", "last_name": "Sakai", "name": null }, { "creator_type": "author", "first_name": "Katsuji", "last_name": "Takeda", "name": null }, { "creator_type": "author", "first_name": "Naoki", "last_name": "Teraya", "name": null }, { "creator_type": "author", "first_name": "Ken", "last_name": "Asada", "name": null }, { "creator_type": "author", "first_name": "Syuzo", "last_name": "Kaneko", "name": null }, { "creator_type": "author", "first_name": "Kazuki", "last_name": "Iwamoto", "name": null }, { "creator_type": "author", "first_name": "Ryu", "last_name": "Matsuoka", "name": null }, { "creator_type": "author", "first_name": "Akihiko", "last_name": "Sekizawa", "name": null }, { "creator_type": "author", "first_name": "Ryuji", "last_name": "Hamamoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.3390/bioengineering11121256" }, "pmcid": { "normalized": "PMC11673077" }, "pmid": { "normalized": "39768074" } }, "mesh": [], "publication": { "conference_name": null, "date": "2024 Dec 12", "date_precision": "day", "issue": "12", "normalized_date": "2024-12-12", "pages": "", "proceedings_title": null, "publisher": "", "title": "Bioengineering (Basel, Switzerland)", "volume": "11", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Automated Assessment of the Pulmonary Artery-to-Ascending Aorta Ratio in Fetal Cardiac Ultrasound Screening Using Artificial Intelligence.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The sympathetic nervous system is crucial for responding to environmental changes. This regulation is coordinated by the spinal sympathetic preganglionic neurons (SPNs), innervating both postganglionic neurons and the adrenal gland. Despite decades of research supporting the concept of selective control within this system, the neural circuit organization responsible for the output specificity remains poorly understood. Here, by combining recent single-cell transcriptome data with viral-genetic toolkits in mice, we identify two subtypes of SPNs in the lower thoracic spinal cord, defined at the molecular level, exhibiting nonoverlapping patterns of innervation: one specifically projecting to the celiac/superior mesenteric ganglia, and the other targeting the adrenal grand. Chemogenetic manipulations on these distinct SPN subtypes revealed selective impacts on the motility of the gastrointestinal tracts or glucose metabolism mediated by the adrenal gland, respectively. This molecularly delineated parallel labeled-line organization in sympathetic outflows presents a potential avenue for selectively manipulating organ functions.", "classifications": [ { "id": "JPMJCR2021", "label": "JPMJCR2021", "researcher": "Hideki Enomoto", "type": "grant" }, { "id": "Enomoto", "label": "Group Enomoto", "parent": "Enomoto", "type": "group" }, { "id": "Miyamichi", "label": "Group Miyamichi", "parent": "Enomoto", "type": "group" }, { "id": "Enomoto", "label": "Team Enomoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yukiko", "last_name": "Harima", "name": null }, { "creator_type": "author", "first_name": "Masafumi", "last_name": "Tsurutani", "name": null }, { "creator_type": "author", "first_name": "Serika", "last_name": "Yamada", "name": null }, { "creator_type": "author", "first_name": "Shuntaro", "last_name": "Uchida", "name": null }, { "creator_type": "author", "first_name": "Kengo", "last_name": "Inada", "name": null }, { "creator_type": "author", "first_name": "Mitsue", "last_name": "Hagihara", "name": null }, { "creator_type": "author", "first_name": "Satsuki", "last_name": "Irie", "name": null }, { "creator_type": "author", "first_name": "Mayo", "last_name": "Shigeta", "name": null }, { "creator_type": "author", "first_name": "Takaya", "last_name": "Abe", "name": null }, { "creator_type": "author", "first_name": "Yukiko U.", "last_name": "Inoue", "name": null }, { "creator_type": "author", "first_name": "Takayoshi", "last_name": "Inoue", "name": null }, { "creator_type": "author", "first_name": "Kazunari", "last_name": "Miyamichi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41467-024-54928-1" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "39658565" } }, "mesh": [ { "descriptor": "Adrenal Glands", "descriptor_ui": "D000311", "major_topic": true }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Ganglia, Sympathetic", "descriptor_ui": "D005728", "major_topic": true }, { "descriptor": "Gastrointestinal Tract", "descriptor_ui": "D041981", "major_topic": false }, { "descriptor": "Glucose", "descriptor_ui": "D005947", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Single-Cell Analysis", "descriptor_ui": "D059010", "major_topic": false }, { "descriptor": "Spinal Cord", "descriptor_ui": "D013116", "major_topic": true }, { "descriptor": "Sympathetic Nervous System", "descriptor_ui": "D013564", "major_topic": true }, { "descriptor": "Transcriptome", "descriptor_ui": "D059467", "major_topic": false } ], "publication": { "conference_name": null, "date": "2024 Dec 10", "date_precision": "day", "issue": "1", "normalized_date": "2024-12-10", "pages": "10478", "proceedings_title": null, "publisher": "", "title": "Nature communications", "volume": "15", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Parallel labeled-line organization of sympathetic outflow for selective organ regulation in mice.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The orchestration of our genes heavily relies on coordinated communication between enhancers and promoters, yet the mechanisms behind this dynamic interplay during active transcription remain unclear. Here, we investigated enhancer-promoter (E-P) interactions in relation to transcriptional bursting in mouse embryonic stem cells using sequential DNA/RNA/immunofluorescence–fluorescence in situ hybridization analyses. Our data reveal that the active state of specific genes is characterized by specific proximities between different genomic regions and the accumulation of transcriptional regulatory factors. Mathematical simulations suggest that an increase in local viscosity could potentially contribute to stabilizing the duration of these E-P proximities. Our study provides insights into the association among E-P proximity, protein accumulation, and transcriptional dynamics, paving the way for a more nuanced understanding of gene-specific regulatory mechanisms.", "classifications": [ { "id": "Onami", "label": "Group Onami", "parent": "Fujiwara", "type": "group" }, { "id": "Fujiwara", "label": "Team Fujiwara", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Hiroaki", "last_name": "Ohishi", "name": null }, { "creator_type": "author", "first_name": "Soya", "last_name": "Shinkai", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Owada", "name": null }, { "creator_type": "author", "first_name": "Takeru", "last_name": "Fujii", "name": null }, { "creator_type": "author", "first_name": "Kazufumi", "last_name": "Hosoda", "name": null }, { "creator_type": "author", "first_name": "Shuichi", "last_name": "Onami", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Yasuyuki", "last_name": "Ohkawa", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Ochiai", "name": null } ], "identifiers": { "doi": { "normalized": "10.1126/sciadv.adn0020" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "39642226" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Enhancer Elements, Genetic", "descriptor_ui": "D004742", "major_topic": true }, { "descriptor": "Gene Expression Regulation", "descriptor_ui": "D005786", "major_topic": false }, { "descriptor": "Genome", "descriptor_ui": "D016678", "major_topic": false }, { "descriptor": "In Situ Hybridization, Fluorescence", "descriptor_ui": "D017404", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mouse Embryonic Stem Cells", "descriptor_ui": "D000066450", "major_topic": true }, { "descriptor": "Promoter Regions, Genetic", "descriptor_ui": "D011401", "major_topic": true }, { "descriptor": "Transcription Factors", "descriptor_ui": "D014157", "major_topic": false }, { "descriptor": "Transcription, Genetic", "descriptor_ui": "D014158", "major_topic": true } ], "publication": { "conference_name": null, "date": "2024 Dec 06", "date_precision": "day", "issue": "49", "normalized_date": "2024-12-06", "pages": "", "proceedings_title": null, "publisher": "", "title": "Science Advances", "volume": "10", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Transcription-coupled changes in genomic region proximities during transcriptional bursting.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Assessing objective physical function in patients with cancer is crucial for evaluating their ability to tolerate invasive treatments. Current assessment methods, such as the timed up and go (TUG) test and the short physical performance battery, tend to require additional resources and time, limiting their practicality in routine clinical practice. To address these challenges, we developed a system to assess physical function based on movements observed during clinical consultations and aimed to explore relevant features from inertial measurement unit data collected during those movements. As for the flow of the research, we first collected inertial measurement unit data from 61 patients with cancer while they replicated a series of movements in a consultation room. We then conducted correlation analyses to identify keypoints of focus and developed machine learning models to predict the TUG test outcomes using the extracted features. Regarding results, pelvic velocity variability (PVV) was identified using Lasso regression. A linear regression model using PVV as the input variable achieved a mean absolute error of 1.322 s and a correlation of 0.713 with the measured TUG results during five-fold cross-validation. Higher PVV correlated with shorter TUG test results. These findings provide a foundation for the development of an artificial intelligence-based physical function assessment system that operates without the need for additional resources.", "classifications": [ { "id": "Hamamoto", "label": "Group Hamamoto", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Nobuji", "last_name": "Kouno", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Ken", "last_name": "Takasawa", "name": null }, { "creator_type": "author", "first_name": "Masaaki", "last_name": "Komatsu", "name": null }, { "creator_type": "author", "first_name": "Naoaki", "last_name": "Ishiguro", "name": null }, { "creator_type": "author", "first_name": "Katsuji", "last_name": "Takeda", "name": null }, { "creator_type": "author", "first_name": "Ayumu", "last_name": "Matsuoka", "name": null }, { "creator_type": "author", "first_name": "Maiko", "last_name": "Fujimori", "name": null }, { "creator_type": "author", "first_name": "Kazuki", "last_name": "Yokoyama", "name": null }, { "creator_type": "author", "first_name": "Shun", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Yoshitaka", "last_name": "Honma", "name": null }, { "creator_type": "author", "first_name": "Ken", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Kazutaka", "last_name": "Obama", "name": null }, { "creator_type": "author", "first_name": "Ryuji", "last_name": "Hamamoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.3390/bioengineering11121232" }, "pmcid": { "normalized": "PMC11673146" }, "pmid": { "normalized": "39768050" } }, "mesh": [], "publication": { "conference_name": null, "date": "2024 Dec 5", "date_precision": "day", "issue": "12", "normalized_date": "2024-12-05", "pages": "", "proceedings_title": null, "publisher": "", "title": "Bioengineering (Basel, Switzerland)", "volume": "11", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Analysis of Inertial Measurement Unit Data for an AI-Based Physical Function Assessment System Using In-Clinic-like Movements.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Oscillatory phenomena play widespread roles in the control of biological systems. In D. discoideum, oscillatory cyclic adenosine monophosphate (cAMP) signaling drives collective behavior and induces a temporal developmental gene expression program. How collective cAMP oscillations emerge or how they encode temporal transcriptional information is still poorly understood. To address this, we identified a transcription factor required for the initiation of collective behavior. Hbx5 activity is cAMP dependent and provides a sensitive single-cell readout for cAMP signaling. Extensive stochastic pulsatile cAMP signaling is found to precede collective oscillations. Stochastic signaling induces Hbx5-dependent transcriptional feedback, which enhances signal sensitivity and cell-cell coupling. This results in the emergence of synchronized collective oscillations, which subsequently activates the GtaC transcription factor and triggers shifts in developmental gene expression. Our results suggest this temporal coordination is encoded by changes in the amplitude of cAMP oscillations and differential sensitivity of these transcription factors to the cAMP-regulated kinase ErkB.", "classifications": [ { "id": "Sawai", "label": "Group Sawai", "parent": "Sawai", "type": "group" }, { "id": "Sawai", "label": "Team Sawai", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Christopher A.", "last_name": "Brimson", "name": null }, { "creator_type": "author", "first_name": "Robert", "last_name": "Baines", "name": null }, { "creator_type": "author", "first_name": "Elisabeth", "last_name": "Sams-Dodd", "name": null }, { "creator_type": "author", "first_name": "Ioanina", "last_name": "Stefanescu", "name": null }, { "creator_type": "author", "first_name": "Bethany", "last_name": "Evans", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Kuwana", "name": null }, { "creator_type": "author", "first_name": "Hidenori", "last_name": "Hashimura", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Sawai", "name": null }, { "creator_type": "author", "first_name": "Christopher R. L.", "last_name": "Thompson", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.devcel.2024.11.016" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "39672161" } }, "mesh": [ { "descriptor": "Cyclic AMP", "descriptor_ui": "D000242", "major_topic": true }, { "descriptor": "Dictyostelium", "descriptor_ui": "D004023", "major_topic": true }, { "descriptor": "Gene Expression Regulation, Developmental", "descriptor_ui": "D018507", "major_topic": false }, { "descriptor": "Protozoan Proteins", "descriptor_ui": "D015800", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": true }, { "descriptor": "Transcription Factors", "descriptor_ui": "D014157", "major_topic": false } ], "publication": { "conference_name": null, "date": "2024 Dec 5", "date_precision": "day", "issue": "", "normalized_date": "2024-12-05", "pages": "S1534-5807(24)00698-1", "proceedings_title": null, "publisher": "", "title": "Developmental cell", "volume": "", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Collective oscillatory signaling in Dictyosteliumdiscoideum acts as a developmental timer initiated by weak coupling of a noisy pulsatile signal.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The cellular slime mold Dictyostelium discoideum, a member of the Amoebozoa, has been extensively studied in cell and developmental biology. D. discoideum is unique in that they are genetically tractable, with a wealth of data accumulated over half a century of research. Fluorescence live-cell imaging of D. discoideum has greatly facilitated studies on fundamental topics, including cytokinesis, phagocytosis, and cell migration. Additionally, its unique life cycle places Dictyostelium at the forefront of understanding aggregative multicellularity, a recurring evolutionary trait found across the Opisthokonta and Amoebozoa clades. The use of multiple fluorescent proteins (FP) and labels with separable spectral properties is critical for tracking cells in aggregates and identifying co-occurring biomolecular events and factors that underlie the dynamics of the cytoskeleton, membrane lipids, second messengers, and gene expression. However, in D. discoideum, the number of frequently used FP species is limited to two or three. In this study, we explored the use of new-generation FP for practical 4- to 5-color fluorescence imaging of D. discoideum. We showed that the yellow fluorescent protein Achilles and the red fluorescent protein mScarlet-I both yield high signals and allow sensitive detection of rapid gene induction. The color palette was further expanded to include blue (mTagBFP2 and mTurquosie2), large Stoke-shift LSSmGFP, and near-infrared (miRFP670nano3) FPs, in addition to the HaloTag ligand SaraFluor 650T. Thus, we demonstrated the feasibility of deploying 4- and 5- color imaging of D. discoideum using conventional confocal microscopy.Key words: fluorescence imaging, organelle, cytoskeleton, small GTPase, Dictyostelium.", "classifications": [ { "id": "JPMJCR1923", "label": "JPMJCR1923", "researcher": "Satoshi Sawai", "type": "grant" }, { "id": "Sawai", "label": "Group Sawai", "parent": "Sawai", "type": "group" }, { "id": "Sawai", "label": "Team Sawai", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Hidenori", "last_name": "Hashimura", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Kuwana", "name": null }, { "creator_type": "author", "first_name": "Hibiki", "last_name": "Nakagwa", "name": null }, { "creator_type": "author", "first_name": "Kenichi", "last_name": "Abe", "name": null }, { "creator_type": "author", "first_name": "Tomoko", "last_name": "Adachi", "name": null }, { "creator_type": "author", "first_name": "Toyoko", "last_name": "Sugita", "name": null }, { "creator_type": "author", "first_name": "Shoko", "last_name": "Fujishiro", "name": null }, { "creator_type": "author", "first_name": "Gen", "last_name": "Honda", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Sawai", "name": null } ], "identifiers": { "doi": { "normalized": "10.1247/csf.24065" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "39631875" } }, "mesh": [ { "descriptor": "Dictyostelium", "descriptor_ui": "D004023", "major_topic": true }, { "descriptor": "Luminescent Proteins", "descriptor_ui": "D008164", "major_topic": true }, { "descriptor": "Microscopy, Fluorescence", "descriptor_ui": "D008856", "major_topic": false }, { "descriptor": "Red Fluorescent Protein", "descriptor_ui": "D000097573", "major_topic": false } ], "publication": { "conference_name": null, "date": "2024 Dec 4", "date_precision": "day", "issue": "", "normalized_date": "2024-12-04", "pages": "", "proceedings_title": null, "publisher": "", "title": "Cell structure and function", "volume": "", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Multi-color fluorescence live-cell imaging in Dictyostelium discoideum.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Hyalinized clear cell carcinoma (HCCC) is a rare tumor of the minor salivary gland, characterized by pale cytoplasm and EWSR1::ATF1 fusion. Recently, new fusions such as EWSR1::LARP4 and SMARCA2::CREM have also been identified. Histologically, HCCC closely resembles other salivary gland tumors like mucoepidermoid carcinoma and myoepithelial carcinoma, and there are no specific immunohistological markers for its identification. In this study, we investigated potential markers for HCCC based on the characteristics of minor salivary gland acini, from which these tumors may originate. SOX10 is a known marker for serous gland clusters and NKX3.1 for mucus gland clusters. Fluorescence intensity analysis of double staining, objectively evaluated by AI, revealed variations in the positive intensity of cells single positive for NKX3.1 and SOX10, as well as cells positive for both markers, which are commonly observed in normal minor salivary glands. We evaluated NKX3.1 expression by immunohistochemistry in 12 HCCC cases (including 9 EWSR1::ATF1, one EWSR1::LARP4, and one SMARCA2::CREM), 12 myoepithelial carcinoma cases and Tissue micro array (TMA) containing 88 cases of multiple salivary gland tumors using immunohistochemistry. NKX3.1 was expressed in all 12 HCCC cases (100%), with NKX3.1-positive cells >==90% in four 3 cases, >==60% one case, >==30% five 4 cases, and <30% two 4 cases, respectively. SOX10 was negative in 10 cases and weakly positive in 2 cases. This finding mimics the pattern of expression in minor salivary glands and may explain the occurrence of weak NKX3.1 staining and SOX10 positive cases in HCCC. Additionally, in the TMA analysis, NKX3.1 staining was observed in only one HCCC case. These findings indicate that NKX3.1 is a useful marker for distinguishing HCCC from other clear cell salivary gland neoplasms. This study suggests that NKX3.1, along with SOX10 and CK7, can be utilized to improve the accuracy of HCCC diagnosis.", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Airi", "last_name": "Sakyo", "name": null }, { "creator_type": "author", "first_name": "Eijitsu", "last_name": "Ryo", "name": null }, { "creator_type": "author", "first_name": "Shogo", "last_name": "Nishino", "name": null }, { "creator_type": "author", "first_name": "Kenya", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Seiichi", "last_name": "Yoshimoto", "name": null }, { "creator_type": "author", "first_name": "Go", "last_name": "Omura", "name": null }, { "creator_type": "author", "first_name": "Chihiro", "last_name": "Fushimi", "name": null }, { "creator_type": "author", "first_name": "Toshihiko", "last_name": "Sakai", "name": null }, { "creator_type": "author", "first_name": "Azusa", "last_name": "Sakai", "name": null }, { "creator_type": "author", "first_name": "Kohtaro", "last_name": "Eguchi", "name": null }, { "creator_type": "author", "first_name": "Hideaki", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Kazuki", "last_name": "Yokoyama", "name": null }, { "creator_type": "author", "first_name": "Yoshitaka", "last_name": "Honma", "name": null }, { "creator_type": "author", "first_name": "Akiko", "last_name": "Mori", "name": null }, { "creator_type": "author", "first_name": "Hiroko", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Toshiyuki", "last_name": "Hatano", "name": null }, { "creator_type": "author", "first_name": "Akihiko", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Fumihiko", "last_name": "Matsumoto", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null }, { "creator_type": "author", "first_name": "Taisuke", "last_name": "Mori", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.labinv.2024.102205" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "39617100" } }, "mesh": [ { "descriptor": "Adenocarcinoma, Clear Cell", "descriptor_ui": "D018262", "major_topic": true }, { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Biomarkers, Tumor", "descriptor_ui": "D014408", "major_topic": true }, { "descriptor": "Diagnosis, Differential", "descriptor_ui": "D003937", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Homeodomain Proteins", "descriptor_ui": "D018398", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Immunohistochemistry", "descriptor_ui": "D007150", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Salivary Gland Neoplasms", "descriptor_ui": "D012468", "major_topic": true }, { "descriptor": "SOXE Transcription Factors", "descriptor_ui": "D055757", "major_topic": false }, { "descriptor": "Transcription Factors", "descriptor_ui": "D014157", "major_topic": true } ], "publication": { "conference_name": null, "date": "2024 Nov 29", "date_precision": "day", "issue": "", "normalized_date": "2024-11-29", "pages": "102205", "proceedings_title": null, "publisher": "", "title": "Laboratory investigation; a journal of technical methods and pathology", "volume": "", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "NKX3.1 helps distinguish hyalinizing clear cell carcinoma from other clear cell salivary gland neoplasms.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Ischemic heart disease is the main global cause of death in the world. Abnormal sulfide catabolism, especially hydrogen sulfide accumulation, impedes mitochondrial respiration and worsens the prognosis after ischemic insults, but the substantial therapeutic strategy has not been established. Non-thermal atmospheric pressure plasma irradiation therapy is attracted attention as it exerts beneficial effects by producing various reactive molecular species. Growing evidence has suggested that supersulfides, formed by catenation of sulfur atoms, contribute to various biological processes involving electron transfer in cells. Here, we report that non-thermal plasma-irradiated cysteine (Cys *) protects mouse hearts against ischemia/reperfusion (I/R) injury by preventing supersulfide catabolism. Cys * has a weak but long-lasting supersulfide activity, and the treatment of rat cardiomyocytes with Cys * prevents mitochondrial dysfunction after hypoxic stress. Cys * increases sulfide-quinone oxidoreductase (SQOR), and silencing SQOR abolishes Cys *-induced supersulfide formation and cytoprotection. Local administration of mouse hearts with Cys * significantly reduces infarct size with preserving supersulfide levels after I/R. These results suggest that maintaining supersulfide formation through SQOR underlies cardioprotection by Cys * against I/R injury.", "classifications": [ { "id": "JPMJCR2024", "label": "JPMJCR2024", "researcher": "Motohiro Nishida", "type": "grant" }, { "id": "Akaike", "label": "Group Akaike", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Group Nishida", "parent": "Nishida", "type": "group" }, { "id": "Nishimura", "label": "Group Nishimura", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Akiyuki", "last_name": "Nishimura", "name": null }, { "creator_type": "author", "first_name": "Tomohiro", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Kakeru", "last_name": "Shimoda", "name": null }, { "creator_type": "author", "first_name": "Tomoaki", "last_name": "Ida", "name": null }, { "creator_type": "author", "first_name": "Shota", "last_name": "Sasaki", "name": null }, { "creator_type": "author", "first_name": "Keitaro", "last_name": "Umezawa", "name": null }, { "creator_type": "author", "first_name": "Hiromi", "last_name": "Imamura", "name": null }, { "creator_type": "author", "first_name": "Yasuteru", "last_name": "Urano", "name": null }, { "creator_type": "author", "first_name": "Fumito", "last_name": "Ichinose", "name": null }, { "creator_type": "author", "first_name": "Toshiro", "last_name": "Kaneko", "name": null }, { "creator_type": "author", "first_name": "Takaaki", "last_name": "Akaike", "name": null }, { "creator_type": "author", "first_name": "Motohiro", "last_name": "Nishida", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.redox.2024.103445" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "39637599" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cysteine", "descriptor_ui": "D003545", "major_topic": true }, { "descriptor": "Disease Models, Animal", "descriptor_ui": "D004195", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Myocardial Reperfusion Injury", "descriptor_ui": "D015428", "major_topic": true }, { "descriptor": "Myocytes, Cardiac", "descriptor_ui": "D032383", "major_topic": false }, { "descriptor": "Plasma Gases", "descriptor_ui": "D058626", "major_topic": true }, { "descriptor": "Quinone Reductases", "descriptor_ui": "D011808", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Sulfides", "descriptor_ui": "D013440", "major_topic": true } ], "publication": { "conference_name": null, "date": "2024 Nov 28", "date_precision": "day", "issue": "", "normalized_date": "2024-11-28", "pages": "103445", "proceedings_title": null, "publisher": "", "title": "Redox biology", "volume": "79", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Non-thermal atmospheric pressure plasma-irradiated cysteine protects cardiac ischemia/reperfusion injury by preserving supersulfides.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "A critical aspect of the mechanism of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is the protease-mediated activation of the viral spike (S) protein. The type II transmembrane serine protease TMPRSS2 is crucial for SARS-CoV-2 infection in lung epithelial Calu-3 cells and murine airways. However, the importance of TMPRSS2 needs to be re-examined because the ability to utilize TMPRSS2 is significantly reduced in the Omicron variants that spread globally. For this purpose, replication profiles of SARS-CoV-2 were analyzed in human respiratory organoids. All tested viruses, including Omicron variants, replicated efficiently in these organoids. Notably, all SARS-CoV-2 strains retained replication ability in TMPRSS2-gene knockout (KO) respiratory organoids, suggesting that TMPRSS2 is not essential for SARS-CoV-2 infection in human respiratory tissues. However, TMPRSS2-gene knockout significantly reduces the inhibitory effect of nafamostat, indicating the advantage of TMPRSS2-utilizing ability for the SARS-CoV-2 infection in these organoids. Interestingly, Omicron variants regained the TMPRSS2-utilizing ability in recent subvariants. The basal infectivity would be supported mainly by cathepsins because the cathepsin inhibitor, EST, showed a significant inhibitory effect on infection with any SARS-CoV-2 strains, mainly when used with nafamostat. A supplementary contribution of other serine proteases was also suggested because the infection of the Delta variant was still inhibited partially by nafamostat in TMPRSS2 KO organoids. Thus, various proteases, including TMPRSS2, other serine proteases, and cathepsins, co-operatively contribute to SARS-CoV-2 infection significantly in the respiratory organoids. Thus, SARS-CoV-2 infection in the human respiratory tissues would be more complex than observed in cell lines or mice. IMPORTANCE: We explored how the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus infects human respiratory organoids, which are a cultured cell model made to mimic the physiological conditions of the human airways. We focused on understanding the role of different proteases of host cells in activating the virus spike proteins. Specifically, we looked at TMPRSS2, a transmembrane serine protease, and cathepsin L, a lysosomal enzyme, which helps the virus enter cells by cutting the viral spike protein. We discovered that while TMPRSS2 is crucial for the virus in certain cells and animal models, other proteases, including cathepsins and various serine proteases, also play significant roles in the SARS-CoV-2 infection of human respiratory organoids. We suggest that SARS-CoV-2 uses a more complex mechanism involving multiple proteases to infect human airways, differing from what we see in conventional cell lines or animal models. This complexity might help explain how different variants can spread and infect people effectively.", "classifications": [ { "id": "Yamamoto", "label": "Group Yamamoto", "parent": "Toyoshima", "type": "group" }, { "id": "Toyoshima", "label": "Team Toyoshima", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Masatoshi", "last_name": "Kakizaki", "name": null }, { "creator_type": "author", "first_name": "Rina", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Noriyo", "last_name": "Nagata", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Okura", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Katoh", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Kitai", "name": null }, { "creator_type": "author", "first_name": "Yukiko", "last_name": "Akahori", "name": null }, { "creator_type": "author", "first_name": "Kazuya", "last_name": "Shirato", "name": null }, { "creator_type": "author", "first_name": "Akihide", "last_name": "Ryo", "name": null }, { "creator_type": "author", "first_name": "Kazuo", "last_name": "Takayama", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Takeda", "name": null } ], "identifiers": { "doi": { "normalized": "10.1128/jvi.01853-24" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "39601592" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Benzamidines", "descriptor_ui": "D001550", "major_topic": false }, { "descriptor": "Cathepsin L", "descriptor_ui": "D056668", "major_topic": true }, { "descriptor": "Cathepsins", "descriptor_ui": "D002403", "major_topic": true }, { "descriptor": "COVID-19", "descriptor_ui": "D000086382", "major_topic": true }, { "descriptor": "Gene Knockout Techniques", "descriptor_ui": "D055786", "major_topic": false }, { "descriptor": "Guanidines", "descriptor_ui": "D006146", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Lung", "descriptor_ui": "D008168", "major_topic": false }, { "descriptor": "Organoids", "descriptor_ui": "D009940", "major_topic": true }, { "descriptor": "SARS-CoV-2", "descriptor_ui": "D000086402", "major_topic": true }, { "descriptor": "Serine Endopeptidases", "descriptor_ui": "D012697", "major_topic": true }, { "descriptor": "Spike Glycoprotein, Coronavirus", "descriptor_ui": "D064370", "major_topic": false }, { "descriptor": "Virus Replication", "descriptor_ui": "D014779", "major_topic": false } ], "publication": { "conference_name": null, "date": "2024 Nov 27", "date_precision": "day", "issue": "", "normalized_date": "2024-11-27", "pages": "e0185324", "proceedings_title": null, "publisher": "", "title": "Journal of virology", "volume": "", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "The respective roles of TMPRSS2 and cathepsins for SARS-CoV-2 infection in human respiratory organoids.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Although a widely used and important industrial chemical, carbon disulfide (CS2) also poses a number of hazards due to its volatility and toxicity. As such, the development of multifunctional materials for the selective capture and easy recognition of CS2 is one of the crucial issues. Herein, we demonstrate completely selective CS2 adsorption among trials involving H2O, alcohols, volatile organic compounds (including thiol derivatives), N2, H2, O2, CH4, CO, NO, and CO2. We also showcase its fine detection using remarkable luminescent response in an Au(I)-based metal-organic framework (MOF) of ZnII(pz)[AuI(CN)2]2 (pz = pyrazine; 1) with a two-fold interpenetration network. Ex situ single crystal X-ray diffraction for 1 and CS2 accommodated 1 suggested that the Au...Au atoms are not only luminescent centers but also act as interaction sites for CS2 modulating the Au...Au contacts. These experiments revealed the specificity of CS2 and how changes in the CS2-induced structure. Based on the obtained structural formation, 1 exhibited a sensitive detecting ability for CS2 with an ultrafast response time of less than 10 s. Ex situ time-resolved photoluminescence analyses developed in this work implied that CS2 varied the energetic relaxation at the excited states related to the luminescent efficiency of the resultant MOF system.", "classifications": [ { "id": "Hijikata", "label": "Group Hijikata", "parent": "Tsuchiya", "type": "group" }, { "id": "Tsuchiya", "label": "Team Tsuchiya", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Haruka", "last_name": "Yoshino", "name": null }, { "creator_type": "author", "first_name": "Masaki", "last_name": "Saigo", "name": null }, { "creator_type": "author", "first_name": "Takumi", "last_name": "Ehara", "name": null }, { "creator_type": "author", "first_name": "Kiyoshi", "last_name": "Miyata", "name": null }, { "creator_type": "author", "first_name": "Ken", "last_name": "Onda", "name": null }, { "creator_type": "author", "first_name": "Jenny", "last_name": "Pirillo", "name": null }, { "creator_type": "author", "first_name": "Yuh", "last_name": "Hijikata", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Takaishi", "name": null }, { "creator_type": "author", "first_name": "Wataru", "last_name": "Kosaka", "name": null }, { "creator_type": "author", "first_name": "Keni-Ichi", "last_name": "Otake", "name": null }, { "creator_type": "author", "first_name": "Susumu", "last_name": "Kitagawa", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Miyasaka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/anie.202413830" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "39592409" } }, "mesh": [], "publication": { "conference_name": null, "date": "2024 Nov 26", "date_precision": "day", "issue": "", "normalized_date": "2024-11-26", "pages": "e202413830", "proceedings_title": null, "publisher": "", "title": "Angewandte Chemie (International ed. in English)", "volume": "", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Ultrafast Luminescence Detection with Selective Adsorption of Carbon Disulfide in a Gold(I) Metal-Organic Framework.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "", "classifications": [ { "id": "Akaike", "label": "Group Akaike", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Hiroki", "last_name": "Sekine", "name": null }, { "creator_type": "author", "first_name": "Haruna", "last_name": "Takeda", "name": null }, { "creator_type": "author", "first_name": "Norihiko", "last_name": "Takeda", "name": null }, { "creator_type": "author", "first_name": "Akihiro", "last_name": "Kishino", "name": null }, { "creator_type": "author", "first_name": "Hayato", "last_name": "Anzawa", "name": null }, { "creator_type": "author", "first_name": "Takayuki", "last_name": "Isagawa", "name": null }, { "creator_type": "author", "first_name": "Nao", "last_name": "Ohta", "name": null }, { "creator_type": "author", "first_name": "Shohei", "last_name": "Murakami", "name": null }, { "creator_type": "author", "first_name": "Hideya", "last_name": "Iwaki", "name": null }, { "creator_type": "author", "first_name": "Nobufumi", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Shu", "last_name": "Kimura", "name": null }, { "creator_type": "author", "first_name": "Zun", "last_name": "Liu", "name": null }, { "creator_type": "author", "first_name": "Koichiro", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Fumiki", "last_name": "Katsuoka", "name": null }, { "creator_type": "author", "first_name": "Masayuki", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Fumihito", "last_name": "Miura", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Masatomo", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Yoshihiro", "last_name": "Izumi", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Fujita", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Yamagata", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Bamba", "name": null }, { "creator_type": "author", "first_name": "Takaaki", "last_name": "Akaike", "name": null }, { "creator_type": "author", "first_name": "Norio", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Kengo", "last_name": "Kinoshita", "name": null }, { "creator_type": "author", "first_name": "Hozumi", "last_name": "Motohashi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s42255-024-01183-9" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "39592844" } }, "mesh": [], "publication": { "conference_name": null, "date": "2024 Nov 26", "date_precision": "day", "issue": "", "normalized_date": "2024-11-26", "pages": "", "proceedings_title": null, "publisher": "", "title": "Nature metabolism", "volume": "", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Author Correction: PNPO-PLP axis senses prolonged hypoxia in macrophages by regulating lysosomal activity.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "We assessed the association between a genome-wide polygenic risk score (PRS) developed for lung adenocarcinoma (LUAD) risk and mutation on the epidermal growth factor receptor (EGFR) gene in 998 East Asian never-smoking female LUAD cases (518 EGFR-positive; 480 EGFR-negative) and 4,544 never-smoking controls using case-case and multinomial regression analyses. We found that the PRS was more strongly associated with EGFR-positive LUAD compared to EGFR-negative LUAD, where the association between the fourth quartile of the PRS and EGFR-positive LUAD (OR=8.63, 95% CI:5.67, 13.14) was significantly higher than the association between the fourth quartile of the PRS with EGFR-negative LUAD (OR=3.50, 95% CI: 2.44, 5.00) (p-heterogeneity=3.66x10(-3)). Our findings suggest that germline genetic susceptibility may be differentially associated with LUAD in never-smoking female East Asian patients depending on the cancer's mutation status, which may have important public health and clinical implications.", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Batel", "last_name": "Blechter", "name": null }, { "creator_type": "author", "first_name": "Chao Agnes", "last_name": "Hsiung", "name": null }, { "creator_type": "author", "first_name": "Xiaoyu", "last_name": "Wang", "name": null }, { "creator_type": "author", "first_name": "Haoyu", "last_name": "Zhang", "name": null }, { "creator_type": "author", "first_name": "Wei Jie", "last_name": "Seow", "name": null }, { "creator_type": "author", "first_name": "Jianxin", "last_name": "Shi", "name": null }, { "creator_type": "author", "first_name": "Nilanjan", "last_name": "Chatterjee", "name": null }, { "creator_type": "author", "first_name": "Hee Nam", "last_name": "Kim", "name": null }, { "creator_type": "author", "first_name": "Maria Pik", "last_name": "Wong", "name": null }, { "creator_type": "author", "first_name": "Yun-Chul", "last_name": "Hong", "name": null }, { "creator_type": "author", "first_name": "Jason Yy", "last_name": "Wong", "name": null }, { "creator_type": "author", "first_name": "Juncheng", "last_name": "Dai", "name": null }, { "creator_type": "author", "first_name": "H. Dean", "last_name": "Hosgood", "name": null }, { "creator_type": "author", "first_name": "Zhaoming", "last_name": "Wang", "name": null }, { "creator_type": "author", "first_name": "I.-Shou", "last_name": "Chang", "name": null }, { "creator_type": "author", "first_name": "Jiyeon", "last_name": "Choi", "name": null }, { "creator_type": "author", "first_name": "Jiucun", "last_name": "Wang", "name": null }, { "creator_type": "author", "first_name": "Minsun", "last_name": "Song", "name": null }, { "creator_type": "author", "first_name": "Wei", "last_name": "Hu", "name": null }, { "creator_type": "author", "first_name": "Wei", "last_name": "Zheng", "name": null }, { "creator_type": "author", "first_name": "Jin Hee", "last_name": "Kim", "name": null }, { "creator_type": "author", "first_name": "Baosen", "last_name": "Zhou", "name": null }, { "creator_type": "author", "first_name": "Demetrius", "last_name": "Albanes", "name": null }, { "creator_type": "author", "first_name": "Min-Ho", "last_name": "Shin", "name": null }, { "creator_type": "author", "first_name": "Lap Ping", "last_name": "Chung", "name": null }, { "creator_type": "author", "first_name": "She-Juan", "last_name": "An", "name": null }, { "creator_type": "author", "first_name": "Hong", "last_name": "Zheng", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null }, { "creator_type": "author", "first_name": "Xu-Chao", "last_name": "Zhang", "name": null }, { "creator_type": "author", "first_name": "Young Tae", "last_name": "Kim", "name": null }, { "creator_type": "author", "first_name": "Xiao-Ou", "last_name": "Shu", "name": null }, { "creator_type": "author", "first_name": "Young-Chul", "last_name": "Kim", "name": null }, { "creator_type": "author", "first_name": "Roel C. H.", "last_name": "Vermeulen", "name": null }, { "creator_type": "author", "first_name": "Bryan A.", "last_name": "Bassig", "name": null }, { "creator_type": "author", "first_name": "Jiang", "last_name": "Chang", "name": null }, { "creator_type": "author", "first_name": "James Chung", "last_name": "Man Ho", "name": null }, { "creator_type": "author", "first_name": "Bu-Tian", "last_name": "Ji", "name": null }, { "creator_type": "author", "first_name": "Michiaki", "last_name": "Kubo", "name": null }, { "creator_type": "author", "first_name": "Yataro", "last_name": "Daigo", "name": null }, { "creator_type": "author", "first_name": "Yukihide", "last_name": "Momozawa", "name": null }, { "creator_type": "author", "first_name": "Yoichiro", "last_name": "Kamatani", "name": null }, { "creator_type": "author", "first_name": "Takayuki", "last_name": "Honda", "name": null }, { "creator_type": "author", "first_name": "Hideo", "last_name": "Kunitoh", "name": null }, { "creator_type": "author", "first_name": "Shun-Ichi", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Yohei", "last_name": "Miyagi", "name": null }, { "creator_type": "author", "first_name": "Haruhiko", "last_name": "Nakayama", "name": null }, { "creator_type": "author", "first_name": "Shingo", "last_name": "Matsumoto", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Tsuboi", "name": null }, { "creator_type": "author", "first_name": "Koichi", "last_name": "Goto", "name": null }, { "creator_type": "author", "first_name": "Zhihua", "last_name": "Yin", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Akiteru", "last_name": "Goto", "name": null }, { "creator_type": "author", "first_name": "Yoshihiro", "last_name": "Minamiya", "name": null }, { "creator_type": "author", "first_name": "Kimihiro", "last_name": "Shimizu", "name": null }, { 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"creator_type": "author", "first_name": "Ming-Shyan", "last_name": "Huang", "name": null }, { "creator_type": "author", "first_name": "Hsien-Chih", "last_name": "Lin", "name": null }, { "creator_type": "author", "first_name": "Adeline", "last_name": "Seow", "name": null }, { "creator_type": "author", "first_name": "Jae Yong", "last_name": "Park", "name": null }, { "creator_type": "author", "first_name": "Sun-Seog", "last_name": "Kweon", "name": null }, { "creator_type": "author", "first_name": "Chien-Jen", "last_name": "Chen", "name": null }, { "creator_type": "author", "first_name": "Yu-Tang", "last_name": "Gao", "name": null }, { "creator_type": "author", "first_name": "Chen", "last_name": "Wu", "name": null }, { "creator_type": "author", "first_name": "Biyun", "last_name": "Qian", "name": null }, { "creator_type": "author", "first_name": "Daru", "last_name": "Lu", "name": null }, { "creator_type": "author", "first_name": "Jianjun", "last_name": "Liu", "name": null }, { "creator_type": "author", "first_name": "Hyo-Sung", "last_name": "Jeon", "name": null }, { "creator_type": "author", "first_name": "Chin-Fu", "last_name": "Hsiao", "name": null }, { "creator_type": "author", "first_name": "Jae Sook", "last_name": "Sung", "name": null }, { "creator_type": "author", "first_name": "Ying-Huang", "last_name": "Tsai", "name": null }, { "creator_type": "author", "first_name": "Yoo Jin", "last_name": "Jung", "name": null }, { "creator_type": "author", "first_name": "Huan", "last_name": "Guo", "name": null }, { "creator_type": "author", "first_name": "Zhibin", "last_name": "Hu", "name": null }, { "creator_type": "author", "first_name": "Tzu-Yu", "last_name": "Chen", "name": null }, { "creator_type": "author", "first_name": "Laurie", "last_name": "Burdett", "name": null }, { "creator_type": "author", "first_name": "Meredith", "last_name": "Yeager", "name": null }, { "creator_type": "author", "first_name": "Amy", "last_name": "Hutchinson", "name": null }, { "creator_type": "author", "first_name": "Sonja I.", "last_name": "Berndt", "name": null }, { "creator_type": "author", "first_name": "Wei", "last_name": "Wu", "name": null }, { "creator_type": "author", "first_name": "Junwen", "last_name": "Wang", "name": null }, { "creator_type": "author", "first_name": "Jin Eun", "last_name": "Choi", "name": null }, { "creator_type": "author", "first_name": "Kyong Hwa", "last_name": "Park", "name": null }, { "creator_type": "author", "first_name": "Sook Whan", "last_name": "Sung", "name": null }, { "creator_type": "author", "first_name": "Li", "last_name": "Liu", "name": null }, { "creator_type": "author", "first_name": "Chang Hyun", "last_name": "Kang", "name": null }, { "creator_type": "author", "first_name": "Chung-Hsing", "last_name": "Chen", "name": null }, { "creator_type": "author", "first_name": "Jun", "last_name": "Xu", "name": null }, { "creator_type": "author", "first_name": "Peng", "last_name": "Guan", "name": null }, { "creator_type": "author", "first_name": "Wen", "last_name": "Tan", "name": null }, { "creator_type": "author", "first_name": "Chih-Liang", "last_name": "Wang", "name": null }, { "creator_type": "author", "first_name": "Alan Dart", "last_name": "Loon Sihoe", "name": null }, { "creator_type": "author", "first_name": "Ying", "last_name": "Chen", "name": null }, { "creator_type": "author", "first_name": "Yi Young", "last_name": "Choi", "name": null }, { "creator_type": "author", "first_name": "Jun Suk", "last_name": "Kim", "name": null }, { "creator_type": "author", "first_name": "Ho-Il", "last_name": "Yoon", "name": null }, { "creator_type": "author", "first_name": "Qiuyin", "last_name": "Cai", "name": null }, { "creator_type": "author", "first_name": "In Kyu", "last_name": "Park", "name": null }, { "creator_type": "author", "first_name": "Ping", "last_name": "Xu", "name": null }, { "creator_type": "author", "first_name": "Qincheng", "last_name": "He", "name": null }, { "creator_type": "author", "first_name": "Chih-Yi", "last_name": "Chen", "name": null }, { "creator_type": "author", "first_name": "Junjie", "last_name": "Wu", "name": null }, { "creator_type": "author", "first_name": "Wei-Yen", "last_name": "Lim", "name": null }, { "creator_type": "author", "first_name": "Kun-Chieh", "last_name": "Chen", "name": null }, { "creator_type": "author", "first_name": "John K. C.", "last_name": "Chan", "name": null }, { "creator_type": "author", "first_name": "Jihua", "last_name": "Li", "name": null }, { "creator_type": "author", "first_name": "Hongyan", "last_name": "Chen", "name": null }, { "creator_type": "author", "first_name": "Chong-Jen", "last_name": "Yu", "name": null }, { "creator_type": "author", "first_name": "Li", "last_name": "Jin", "name": null }, { "creator_type": "author", "first_name": "Joseph F. Jr", "last_name": "Fraumeni", "name": null }, { "creator_type": "author", "first_name": "Jie", "last_name": "Liu", "name": null }, { "creator_type": "author", "first_name": "Maria Teresa", "last_name": "Landi", "name": null }, { "creator_type": "author", "first_name": "Taiki", "last_name": "Yamaji", "name": null }, { "creator_type": "author", "first_name": "Yang", "last_name": "Yang", "name": null }, { "creator_type": "author", "first_name": "Belynda", "last_name": "Hicks", "name": null }, { "creator_type": "author", "first_name": "Kathleen", "last_name": "Wyatt", "name": null }, { "creator_type": "author", "first_name": "Shengchao A.", "last_name": "Li", "name": null }, { "creator_type": "author", "first_name": "Hongxia", "last_name": "Ma", "name": null }, { "creator_type": "author", "first_name": "Bao", "last_name": "Song", "name": null }, { "creator_type": "author", "first_name": "Zhehai", "last_name": "Wang", "name": null }, { "creator_type": "author", "first_name": "Sensen", "last_name": "Cheng", "name": null }, { "creator_type": "author", "first_name": "Xuelian", "last_name": "Li", "name": null }, { "creator_type": "author", "first_name": "Yangwu", "last_name": "Ren", "name": null }, { "creator_type": "author", "first_name": "Motoki", "last_name": "Iwasaki", "name": null }, { "creator_type": "author", "first_name": "Junjie", "last_name": "Zhu", "name": null }, { "creator_type": "author", "first_name": "Gening", "last_name": "Jiang", "name": null }, { "creator_type": "author", "first_name": "Ke", "last_name": "Fei", "name": null }, { "creator_type": "author", "first_name": "Guoping", "last_name": "Wu", "name": null }, { "creator_type": "author", "first_name": "Li-Hsin", "last_name": "Chien", "name": null }, { "creator_type": "author", "first_name": "Fang-Yu", "last_name": "Tsai", "name": null }, { "creator_type": "author", "first_name": "Jinming", "last_name": "Yu", "name": null }, { "creator_type": "author", "first_name": "Victoria L.", "last_name": "Stevens", "name": null }, { "creator_type": "author", "first_name": "Pan-Chyr", "last_name": "Yang", "name": null }, { "creator_type": "author", "first_name": "Dongxin", "last_name": "Lin", "name": null }, { "creator_type": "author", "first_name": "Kexin", "last_name": "Chen", "name": null }, { "creator_type": "author", "first_name": "Yi-Long", "last_name": "Wu", "name": null }, { "creator_type": "author", "first_name": "Keitaro", "last_name": "Matsuo", "name": null }, { "creator_type": "author", "first_name": "Nathaniel", "last_name": "Rothman", "name": null }, { "creator_type": "author", "first_name": "Kouya", "last_name": "Shiraishi", "name": null }, { "creator_type": "author", "first_name": "Hongbing", "last_name": "Shen", "name": null }, { "creator_type": "author", "first_name": "Stephen J.", "last_name": "Chanock", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Kohno", "name": null }, { "creator_type": "author", "first_name": "Qing", "last_name": "Lan", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.jtho.2024.11.019" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "39581378" } }, "mesh": [ { "descriptor": "Adenocarcinoma of Lung", "descriptor_ui": "D000077192", "major_topic": true }, { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Case-Control Studies", "descriptor_ui": "D016022", "major_topic": false }, { "descriptor": "ErbB Receptors", "descriptor_ui": "D066246", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Genetic Predisposition to Disease", "descriptor_ui": "D020022", "major_topic": false }, { "descriptor": "Genetic Risk Score", "descriptor_ui": "D000096442", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Lung Neoplasms", "descriptor_ui": "D008175", "major_topic": true }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Multifactorial Inheritance", "descriptor_ui": "D020412", "major_topic": true }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": true }, { "descriptor": "Non-Smokers", "descriptor_ui": "D000078405", "major_topic": false }, { "descriptor": "Prognosis", "descriptor_ui": "D011379", "major_topic": false }, { "descriptor": "Risk Factors", "descriptor_ui": "D012307", "major_topic": false } ], "publication": { "conference_name": null, "date": "2024 Nov 22", "date_precision": "day", "issue": "", "normalized_date": "2024-11-22", "pages": "S1556-0864(24)02482-1", "proceedings_title": null, "publisher": "", "title": "Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer", "volume": "", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Polygenic risk score and lung adenocarcinoma risk among never-smokers by EGFR mutation status-a brief report.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Nanoporous solids, including metal-organic frameworks (MOFs), have long been known to capture small molecules by adsorption on their pore surfaces. Liquids are also known to accommodate small molecules by dissolution. These two processes have been recognized as fundamentally distinct phenomena because of the different nature of the medium-solids and liquids. Here, we report a dissolution-like gas accommodation so-called \"adsorptive-dissolution\" behavior in a MOF (PFAC-2) with pores densely filled with perfluoroalkyl chains. PFAC-2 does not have solvent-accessible voids; nevertheless, it captures oxygen molecules without changing the framework structure, analogous to molecular dissolution into liquids. Moreover, we demonstrate the selective capture of O(2) by PFAC-2 in a mixture of O(2) and Ar, which are difficult to separate due to their similarities such as boiling point and molecular size. Our results show the integration of molecular adsorption into nanospaces and dissolution into fluorous solvents, which can guide the design of crystalline adsorbents for selective molecular trapping and gas separation.", "classifications": [ { "id": "Hijikata", "label": "Group Hijikata", "parent": "Tsuchiya", "type": "group" }, { "id": "Tsuchiya", "label": "Team Tsuchiya", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Shinpei", "last_name": "Kusaka", "name": null }, { "creator_type": "author", "first_name": "Yuh", "last_name": "Itoh", "name": null }, { "creator_type": "author", "first_name": "Akihiro", "last_name": "Hori", "name": null }, { "creator_type": "author", "first_name": "Junichi", "last_name": "Usuba", "name": null }, { "creator_type": "author", "first_name": "Jenny", "last_name": "Pirillo", "name": null }, { "creator_type": "author", "first_name": "Yuh", "last_name": "Hijikata", "name": null }, { "creator_type": "author", "first_name": "Yunsheng", "last_name": "Ma", "name": null }, { "creator_type": "author", "first_name": "Ryotaro", "last_name": "Matsuda", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41467-024-54391-y" }, "pmcid": { "normalized": "PMC11584617" }, "pmid": { "normalized": "39578463" } }, "mesh": [], "publication": { "conference_name": null, "date": "2024 Nov 22", "date_precision": "day", "issue": "1", "normalized_date": "2024-11-22", "pages": "10117", "proceedings_title": null, "publisher": "", "title": "Nature communications", "volume": "15", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Adsorptive-dissolution of O(2) into the potential nanospace of a densely fluorinated metal-organic framework.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "INTRODUCTION: With the implementation of low-dose computed tomography (LDCT) screening, multiple pulmonary tumor nodules (MPTN) are diagnosed with increasing frequency and the selection of surgical treatments versus systemic therapies has become challenging on a daily basis in clinical practice. In the presence of multiple carcinomas, especially adenocarcinomas, pathologically determined to be of pulmonary origin, the distinction between separate primary lung carcinomas (SPLCs) and intrapulmonary metastases (IPMs) is important for staging, management, and prognostication. METHODS: We systemically reviewed various means that aid in the differentiation between SPLCs and IPMs explored by histopathologic evaluation and molecular profiling, the latter includes DNA microsatellite analysis, array comparative genomic hybridization, TP53 and oncogenic driver mutation testing and, more recently, with promising effectiveness, next-generation sequencing (NGS) comprising small- or large-scale multi-gene panels. RESULTS: Comprehensive histologic evaluation may suffice to differentiate between SPLCs and IPMs. However, molecular profiling using larger-scale NGS typically provides superior discriminatory power, allowing for more accurate classification. Based on the literature review and expert opinions, we proposed a combined 4-step histologic and molecular classification algorithm for addressing MPTN of adenocarcinoma histology that encourages a multidisciplinary approach. It is also noteworthy that new technologies combining machine learning and digital pathology may develop into valuable diagnostic tools for distinguishing SPLCs from IPMs in the future. CONCLUSIONS: Although histopathologic evaluation is often adequate to differentiate SPLCs from IPMs, molecular profiling should be performed when possible, especially in cases with tumors exhibiting similar morphology. This manuscript summarized the previous efforts in resolving the current challenges and highlighted the recent progress in the differentiation methods and algorithms used in categorizing multiple lung adenocarcinomas into SPLCs or IPMs, which are becoming more and more critical in precision lung cancer management.", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Teh-Ying", "last_name": "Chou", "name": null }, { "creator_type": "author", "first_name": "Sanja", "last_name": "Dacic", "name": null }, { "creator_type": "author", "first_name": "Ignacio", "last_name": "Wistuba", "name": null }, { "creator_type": "author", "first_name": "Mary Beth", "last_name": "Beasley", "name": null }, { "creator_type": "author", "first_name": "Sabina", "last_name": "Berezowska", "name": null }, { "creator_type": "author", "first_name": "Yeun-Chung", "last_name": "Chang", "name": null }, { "creator_type": "author", "first_name": "Jin-Haeng", "last_name": "Chung", "name": null }, { "creator_type": "author", "first_name": "Casey", "last_name": "Connolly", "name": null }, { "creator_type": "author", "first_name": "Yuchen", "last_name": "Han", "name": null }, { "creator_type": "author", "first_name": "Fred R.", "last_name": "Hirsch", "name": null }, { "creator_type": "author", "first_name": "David M.", "last_name": "Hwang", "name": null }, { "creator_type": "author", "first_name": "Andrew", "last_name": "Janowczyk", "name": null }, { "creator_type": "author", "first_name": "Philippe", "last_name": "Joubert", "name": null }, { "creator_type": "author", "first_name": "Keith M.", "last_name": "Kerr", "name": null }, { "creator_type": "author", "first_name": "Dongmei", "last_name": "Lin", "name": null }, { "creator_type": "author", "first_name": "Yuko", "last_name": "Minami", "name": null }, { "creator_type": "author", "first_name": "Mari", "last_name": "Mino-Kenudson", "name": null }, { "creator_type": "author", "first_name": "Andrew G.", "last_name": "Nicholson", "name": null }, { "creator_type": "author", "first_name": "Mauro", "last_name": "Papotti", "name": null }, { "creator_type": "author", "first_name": "Natasha", "last_name": "Rekhtman", "name": null }, { "creator_type": "author", "first_name": "Anja C.", "last_name": "Roden", "name": null }, { "creator_type": "author", "first_name": "Erik", "last_name": "Thunnissen", "name": null }, { "creator_type": "author", "first_name": "J. H.", "last_name": "von der Thusen", "name": null }, { "creator_type": "author", "first_name": "William", "last_name": "Travis", "name": null }, { "creator_type": "author", "first_name": "Ming-Sound", "last_name": "Tsao", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null }, { "creator_type": "author", "first_name": "Yi-Chen", "last_name": "Yeh", "name": null }, { "creator_type": "author", "first_name": "Lukas", "last_name": "Bubendorf", "name": null }, { "creator_type": "author", "first_name": "Wei-Chin", "last_name": "Chang", "name": null }, { "creator_type": "author", "first_name": "Valeria", "last_name": "Denninghoff", "name": null }, { "creator_type": "author", "first_name": "Fabio Rocha", "last_name": "Fernandes Tavora", "name": null }, { "creator_type": "author", "first_name": "Takuo", "last_name": "Hayashi", "name": null }, { "creator_type": "author", "first_name": "Paul", "last_name": "Hofman", "name": null }, { "creator_type": "author", "first_name": "Deepali", "last_name": "Jain", "name": null }, { "creator_type": "author", "first_name": "Tae-Jung", "last_name": "Kim", "name": null }, { "creator_type": "author", "first_name": "Sylvie", "last_name": "Lantuejoul", "name": null }, { "creator_type": "author", "first_name": "John", "last_name": "Le Quesne", "name": null }, { "creator_type": "author", "first_name": "Fernando", "last_name": "Lopez-Rios", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Matsubara", "name": null }, { "creator_type": "author", "first_name": "Masayuki", "last_name": "Noguchi", "name": null }, { "creator_type": "author", "first_name": "Teodora", "last_name": "Radonic", "name": null }, { "creator_type": "author", "first_name": "Anjali", "last_name": "Saqi", "name": null }, { "creator_type": "author", "first_name": "Kurt", "last_name": "Schalper", "name": null }, { "creator_type": "author", "first_name": "Hyo Sup", "last_name": "Shim", "name": null }, { "creator_type": "author", "first_name": "Lynette", "last_name": "Sholl", "name": null }, { "creator_type": "author", "first_name": "Annikka", "last_name": "Weissferdt", "name": null }, { "creator_type": "author", "first_name": "Wendy A.", "last_name": "Cooper", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.jtho.2024.11.016" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "39579981" } }, "mesh": [ { "descriptor": "Adenocarcinoma", "descriptor_ui": "D000230", "major_topic": true }, { "descriptor": "Adenocarcinoma of Lung", "descriptor_ui": "D000077192", "major_topic": true }, { "descriptor": "Diagnosis, Differential", "descriptor_ui": "D003937", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Lung Neoplasms", "descriptor_ui": "D008175", "major_topic": true }, { "descriptor": "Neoplasm Metastasis", "descriptor_ui": "D009362", "major_topic": false } ], "publication": { "conference_name": null, "date": "2024 Nov 21", "date_precision": "day", "issue": "", "normalized_date": "2024-11-21", "pages": "S1556-0864(24)02479-1", "proceedings_title": null, "publisher": "", "title": "Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer", "volume": "", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Differentiating separate primary lung adenocarcinomas from intrapulmonary metastases with emphasis on pathological and molecular considerations: Recommendations from the IASLC Pathology Committee.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: A substantial portion of gastric cancer (GC) is linked to Epstein-Barr virus (EBV) infection. The characteristics of this viral genome, such as specific viral strains and large structural variations, influence the progression of diseases like nasopharyngeal carcinoma and hematological malignancy. However, the EBV genomes from GC have not been thoroughly characterized. METHODS: Our study involved 849 consecutive GC patients diagnosed at Nagoya City University Hospital, Japan (NCU cohort). We detected EBV from formalin-fixed, paraffin-embedded sections using a novel direct PCR-based rapid detection method. Additionally, we analyzed 142 EBV whole genomes (125 newly sequenced) from GC, comparing them with 205 genomes from other EBV-associated diseases. RESULTS: We identified 32 (3.8%) patients associated with EBVaGC in the NCU cohort. Moreover, the direct PCR identified several GC specimens containing EBV-infected lymphocytes or their follicles. The dominant viral strain in GC was type 1 EBV, prevalent in most parts of the world, and no GC-specific strain was identified. We found no significant associations between single-nucleotide variants in the viral genome and GC. Structural variations of the EBV genome were infrequent in GC (4 cases, 2.1%), contrasting with EBV-associated hematological malignancy, which frequently carries large deletions. CONCLUSIONS: This study is the first to uncover the genomic variations of EBV in GC. While EBV is definitively linked to GC, the characteristics of its genomes do not strongly correlate with disease development or progression. Our findings on viral genomes supplement the current understanding of human genomes in EBVaGC.", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yuki", "last_name": "Kojima", "name": null }, { "creator_type": "author", "first_name": "Motoharu", "last_name": "Hamada", "name": null }, { "creator_type": "author", "first_name": "Azumi", "last_name": "Naruse", "name": null }, { "creator_type": "author", "first_name": "Kimitoshi", "last_name": "Goto", "name": null }, { "creator_type": "author", "first_name": "Htet Thiri", "last_name": "Khine", "name": null }, { "creator_type": "author", "first_name": "Haruto", "last_name": "Arai", "name": null }, { "creator_type": "author", "first_name": "Yuta", "last_name": "Akutsu", "name": null }, { "creator_type": "author", "first_name": "Akira", "last_name": "Satou", "name": null }, { "creator_type": "author", "first_name": "Masato", "last_name": "Nakaguro", "name": null }, { "creator_type": "author", "first_name": "Seiichi", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Yasuhiro", "last_name": "Kodera", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null }, { "creator_type": "author", "first_name": "Yuka", "last_name": "Torii", "name": null }, { "creator_type": "author", "first_name": "Jun-Ichi", "last_name": "Kawada", "name": null }, { "creator_type": "author", "first_name": "Takayuki", "last_name": "Murata", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Kimura", "name": null }, { "creator_type": "author", "first_name": "Shuji", "last_name": "Takiguchi", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Inagaki", "name": null }, { "creator_type": "author", "first_name": "Hiromi", "last_name": "Kataoka", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Okuno", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/s00535-024-02170-3" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "39572460" } }, "mesh": [ { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Aged, 80 and over", "descriptor_ui": "D000369", "major_topic": false }, { "descriptor": "DNA, Viral", "descriptor_ui": "D004279", "major_topic": false }, { "descriptor": "Epstein-Barr Virus Infections", "descriptor_ui": "D020031", "major_topic": true }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Genome, Viral", "descriptor_ui": "D016679", "major_topic": true }, { "descriptor": "Herpesvirus 4, Human", "descriptor_ui": "D004854", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Japan", "descriptor_ui": "D007564", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Polymerase Chain Reaction", "descriptor_ui": "D016133", "major_topic": false }, { "descriptor": "Stomach Neoplasms", "descriptor_ui": "D013274", "major_topic": true } ], "publication": { "conference_name": null, "date": "2024 Nov 21", "date_precision": "day", "issue": "", "normalized_date": "2024-11-21", "pages": "", "proceedings_title": null, "publisher": "", "title": "Journal of gastroenterology", "volume": "", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "The landscape of 142 Epstein-Barr viral whole genomes in gastric cancer.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Temporal control of transgenes has advanced biomedical interventions, including in vivo reprogramming, often utilizing the doxycycline (Dox)-mediated Tet-ON system. Here, we developed the Dox-mediated Tet-ON or complementary Tet-OFF counterpart to thoroughly investigate spatial and temporal transgene regulation in adult tissues, revealing inherent limitations and unexpected capabilities of each system. In stark contrast with the Tet-ON system, which was effective only in particular tissues and cell types, primarily epithelial cells, the Tet-OFF system proved capable of gene induction across diverse cell types. Despite the drawback of the Tet-OFF system in inducibility and tunability identified in our study, we demonstrated that use of tetracycline (Tc) effectively addresses these issues, possibly through its pharmacologic properties. Our data suggest that the Tc-mediated Tet-OFF system not only enables more versatile control of transgene expression but also offers a more biocompatible alternative for in vivo applications such as tissue regeneration and organismal rejuvenation.", "classifications": [ { "id": "Yamamoto", "label": "Group Yamamoto", "parent": "Toyoshima", "type": "group" }, { "id": "Toyoshima", "label": "Team Toyoshima", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Jumpei", "last_name": "Taguchi", "name": null }, { "creator_type": "author", "first_name": "Yosuke", "last_name": "Yamada", "name": null }, { "creator_type": "author", "first_name": "Sho", "last_name": "Ohta", "name": null }, { "creator_type": "author", "first_name": "Fumie", "last_name": "Nakasuka", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Manabu", "last_name": "Ozawa", "name": null }, { "creator_type": "author", "first_name": "Yasuhiro", "last_name": "Yamada", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.stemcr.2024.11.003" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "39642874" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Doxycycline", "descriptor_ui": "D004318", "major_topic": false }, { "descriptor": "Gene Expression Regulation", "descriptor_ui": "D005786", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Organ Specificity", "descriptor_ui": "D009928", "major_topic": false }, { "descriptor": "Tetracycline", "descriptor_ui": "D013752", "major_topic": false }, { "descriptor": "Transgenes", "descriptor_ui": "D019076", "major_topic": true } ], "publication": { "conference_name": null, "date": "2024 Nov 20", "date_precision": "day", "issue": "", "normalized_date": "2024-11-20", "pages": "S2213-6711(24)00317-5", "proceedings_title": null, "publisher": "", "title": "Stem cell reports", "volume": "", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "A versatile in vivo platform for reversible control of transgene expression in adult tissues.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Sexual desire is a complex construct with important implications for sexual functioning and well-being. In this research, we translated the Sexual Desire Inventory (SDI-2), a widely used scale for assessing sexual (desire), into 25 languages from English and used data from the International Sex Survey (ISS) to (a) investigate its psychometric properties (i.e. factorial structure, reliability, validity, and measurement invariance) and (b) explore the expression of sexual desire across different countries, genders, and sexual orientations. A total of 82,243 participants from 42 countries completed the SDI-2, along with other sexuality-related scales. Confirmatory factor analysis supported a three-factor solution for the SDI-2 (CFI = .980; RMSEA = .060), encompassing the domains of \"Partner-related,\" \"Attractive-person-related,\" and \"Solitary\" sexual desire. The reliability of the total score and subscales were excellent. Likewise, correlations with other sexuality-related variables were positive yet weak-to-moderate in effect size. Measurement invariance tests supported its use across countries, languages, genders, and sexual orientations. Analysis of SDI-2 scores according to these variables supported its ability to capture group-based differences in sexual desire. In sum, the SDI-2 constitutes a psychometrically robust measure for the assessment of sexual desire in non-clinical samples with utility in large-scale cross-cultural studies.", "classifications": [ { "id": "Fujiwara", "label": "Group Fujiwara", "parent": "Fujiwara", "type": "group" }, { "id": "Fujiwara", "label": "Team Fujiwara", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Jesus", "last_name": "Castro-Calvo", "name": null }, { "creator_type": "author", "first_name": "Patricia", "last_name": "Beltran-Martinez", "name": null }, { "creator_type": "author", "first_name": "Rafael", "last_name": "Ballester-Arnal", "name": null }, { "creator_type": "author", "first_name": "Lena", "last_name": "Nagy", "name": null }, { "creator_type": "author", "first_name": "Monika", "last_name": "Koos", "name": null }, { "creator_type": "author", "first_name": "Shane W.", "last_name": "Kraus", "name": null }, { "creator_type": "author", "first_name": "Zsolt", "last_name": "Demetrovics", "name": null }, { "creator_type": "author", "first_name": "Marc N.", "last_name": "Potenza", "name": null }, { "creator_type": "author", "first_name": "Dominik", "last_name": "Batthyany", "name": null }, { "creator_type": "author", "first_name": "Sophie", "last_name": "Bergeron", "name": null }, { "creator_type": "author", "first_name": "Joel", "last_name": "Billieux", "name": null }, { "creator_type": "author", "first_name": "Peer", "last_name": "Briken", "name": null }, { "creator_type": "author", "first_name": "Julius", "last_name": "Burkauskas", "name": null }, { "creator_type": "author", "first_name": "Georgina", "last_name": "Cardenas-Lopez", "name": null }, { "creator_type": "author", "first_name": "Joana", "last_name": "Carvalho", "name": null }, { "creator_type": "author", "first_name": "Lijun", "last_name": "Chen", "name": null }, { "creator_type": "author", "first_name": "Giacomo", "last_name": "Ciocca", "name": null }, { "creator_type": "author", "first_name": "Ornella", "last_name": "Corazza", "name": null }, { "creator_type": "author", "first_name": "Rita", "last_name": "Csako", "name": null }, { "creator_type": "author", "first_name": "David P.", "last_name": "Fernandez", "name": null }, { "creator_type": "author", "first_name": "Elaine F.", "last_name": "Fernandez", "name": null }, { "creator_type": "author", "first_name": "Hironobu", "last_name": "Fujiwara", "name": null }, { "creator_type": "author", "first_name": "Johannes", "last_name": "Fuss", "name": null }, { "creator_type": "author", "first_name": "Roman", "last_name": "Gabrhelik", "name": null }, { "creator_type": "author", "first_name": "Ateret", "last_name": "Gewirtz-Meydan", "name": null }, { "creator_type": "author", "first_name": "Biljana", "last_name": "Gjoneska", "name": null }, { "creator_type": "author", "first_name": "Mateusz", "last_name": "Gola", "name": null }, { "creator_type": "author", "first_name": "Joshua B.", "last_name": "Grubbs", "name": null }, { "creator_type": "author", "first_name": "Hashim T.", "last_name": "Hashim", "name": null }, { "creator_type": "author", "first_name": "Yi-Ping", "last_name": "Hsieh", "name": null }, { "creator_type": "author", "first_name": "Saiful", "last_name": "Islam", "name": null }, { "creator_type": "author", "first_name": "Mustafa", "last_name": "Ismail", "name": null }, { "creator_type": "author", "first_name": "Martha C.", "last_name": "Jimenez-Martinez", "name": null }, { "creator_type": "author", "first_name": "Tanja", "last_name": "Jurin", "name": null }, { "creator_type": "author", "first_name": "Ondrej", "last_name": "Kalina", "name": null }, { "creator_type": "author", "first_name": "Verena", "last_name": "Klein", "name": null }, { "creator_type": "author", "first_name": "Andras", "last_name": "Kolto", "name": null }, { "creator_type": "author", "first_name": "Sang-Kyu", "last_name": "Lee", "name": null }, { "creator_type": "author", "first_name": "Karol", "last_name": "Lewczuk", "name": null }, { "creator_type": "author", "first_name": "Chung-Ying", "last_name": "Lin", "name": null }, { "creator_type": "author", "first_name": "Christine", "last_name": "Lochner", "name": null }, { "creator_type": "author", "first_name": "Silvia", "last_name": "Lopez-Alvarado", "name": null }, { "creator_type": "author", "first_name": "Katerina", "last_name": "Lukavska", "name": null }, { "creator_type": "author", "first_name": "Percy", "last_name": "Mayta-Tristan", "name": null }, { "creator_type": "author", "first_name": "Dan J.", "last_name": "Miller", "name": null }, { "creator_type": "author", "first_name": "Olga", "last_name": "Orosova", "name": null }, { "creator_type": "author", "first_name": "Gabor", "last_name": "Orosz", "name": null }, { "creator_type": "author", "first_name": "Sungkyunkwan University's Research", "last_name": "Team", "name": null }, { "creator_type": "author", "first_name": "Fernando P.", "last_name": "Ponce", "name": null }, { "creator_type": "author", "first_name": "Gonzalo R.", "last_name": "Quintana", "name": null }, { "creator_type": "author", "first_name": "Gabriel C.", "last_name": "Quintero Garzola", "name": null }, { "creator_type": "author", "first_name": "Jano", "last_name": "Ramos-Diaz", "name": null }, { "creator_type": "author", "first_name": "Kevin", "last_name": "Rigaud", "name": null }, { "creator_type": "author", "first_name": "Ann", "last_name": "Rousseau", "name": null }, { "creator_type": "author", "first_name": "Marco", "last_name": "De Tubino Scanavino", "name": null }, { "creator_type": "author", "first_name": "Marion K.", "last_name": "Schulmeyer", "name": null }, { "creator_type": "author", "first_name": "Pratap", "last_name": "Sharan", "name": null }, { "creator_type": "author", "first_name": "Mami", "last_name": "Shibata", "name": null }, { "creator_type": "author", "first_name": "Sheikh", "last_name": "Shoib", "name": null }, { "creator_type": "author", "first_name": "Vera", "last_name": "Sigre-Leiros", "name": null }, { "creator_type": "author", "first_name": "Luke", "last_name": "Sniewski", "name": null }, { "creator_type": "author", "first_name": "Ognen", "last_name": "Spasovski", "name": null }, { "creator_type": "author", "first_name": "Vesta", "last_name": "Steibliene", "name": null }, { "creator_type": "author", "first_name": "Dan J.", "last_name": "Stein", "name": null }, { "creator_type": "author", "first_name": "Aleksandar", "last_name": "Stulhofer", "name": null }, { "creator_type": "author", "first_name": "Berk C.", "last_name": "Unsal", "name": null }, { "creator_type": "author", "first_name": "Marie-Pier", "last_name": "Vaillancourt-Morel", "name": null }, { "creator_type": "author", "first_name": "Marie Claire", "last_name": "Van Hout", "name": null }, { "creator_type": "author", "first_name": "Beata", "last_name": "Bothe", "name": null } ], "identifiers": { "doi": { "normalized": "10.1080/00224499.2024.2417023" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "39560207" } }, "mesh": [ { "descriptor": "Adolescent", "descriptor_ui": "D000293", "major_topic": false }, { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Cross-Cultural Comparison", "descriptor_ui": "D003431", "major_topic": true }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Libido", "descriptor_ui": "D007989", "major_topic": true }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Psychometrics", "descriptor_ui": "D011594", "major_topic": true }, { "descriptor": "Reproducibility of Results", "descriptor_ui": "D015203", "major_topic": false }, { "descriptor": "Sexual Behavior", "descriptor_ui": "D012725", "major_topic": true }, { "descriptor": "Surveys and Questionnaires", "descriptor_ui": "D011795", "major_topic": false }, { "descriptor": "Young Adult", "descriptor_ui": "D055815", "major_topic": false } ], "publication": { "conference_name": null, "date": "2024 Nov 19", "date_precision": "day", "issue": "", "normalized_date": "2024-11-19", "pages": "1-14", "proceedings_title": null, "publisher": "", "title": "Journal of sex research", "volume": "", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Cross-Cultural Validation of the Sexual Desire Inventory (SDI-2) in 42 Countries and 26 Languages.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "PURPOSE: A major problem in establishing treatment strategies for salivary gland carcinomas is the difficulty of preoperative histologic subtyping. Core needle biopsy (CNB) allows the collection of a small, intact specimens from the tumor center for detailed analysis. We evaluated the efficacy and limitations of preoperative diagnosis with CNB specimens collected using a newly developed 20-gauge needle designed to popularize its use. METHODS: Paired preoperative CNB and surgical specimens from 41 patients with malignant salivary gland tumors were retrospectively reviewed. A histologic typing platform, including morphologic and immunohistochemical evaluation and fluorescence in situ hybridization, was evaluated using CNB specimens. Biopsy specimen quality, diagnostic accuracy, and immunohistochemistry concordance rates between biopsy and surgical specimens were analyzed. RESULTS: In 39 of the 41 patients, CNB provided high-quality specimens, enabling adequate morphologic, immunohistologic, and genomic analyses. In two patients, high-quality CNB specimens could not be obtained due to cystic fluid and tumor firmness. The overall accuracy of correct preoperative diagnosis was 75%. The success rate of histologic subtyping and HER2 immunostaining concordance between CNB and surgical specimens was lower in carcinoma ex-pleomorphic adenoma (CXPA) than in de novo carcinoma (histologic subtyping; CXPA vs de novo carcinoma 50% vs 89%, p = 0.016, HER2 concordance; salivary duct carcinoma [SDC] ex-PA vs de novo SDC 16% vs 100%, p = 4.66E-03). No recurrence occurred due to tumor seeding after CNB. CONCLUSIONS: Highly accurate histologic subtyping of salivary gland carcinomas can be performed by preoperative CNB; however, specificity can be more challenging in pathologically heterogenous tumors.", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Kenya", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Seiichi", "last_name": "Yoshimoto", "name": null }, { "creator_type": "author", "first_name": "Go", "last_name": "Omura", "name": null }, { "creator_type": "author", "first_name": "Yoshifumi", "last_name": "Matsumoto", "name": null }, { "creator_type": "author", "first_name": "Azusa", "last_name": "Sakai", "name": null }, { "creator_type": "author", "first_name": "Kohtaro", "last_name": "Eguchi", "name": null }, { "creator_type": "author", "first_name": "Toshihiko", "last_name": "Sakai", "name": null }, { "creator_type": "author", "first_name": "Yoshitaka", "last_name": "Honma", "name": null }, { "creator_type": "author", "first_name": "Fumihiko", "last_name": "Matsumoto", "name": null }, { "creator_type": "author", "first_name": "Masahito", "last_name": "Kawazu", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Eigitsu", "last_name": "Ryo", "name": null }, { "creator_type": "author", "first_name": "Akihiko", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null }, { "creator_type": "author", "first_name": "Taisuke", "last_name": "Mori", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/s12105-024-01725-3" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "39560855" } }, "mesh": [ { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Aged, 80 and over", "descriptor_ui": "D000369", "major_topic": false }, { "descriptor": "Biopsy, Large-Core Needle", "descriptor_ui": "D062005", "major_topic": false }, { "descriptor": "Carcinoma", "descriptor_ui": "D002277", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Pathologists", "descriptor_ui": "D000072142", "major_topic": false }, { "descriptor": "Retrospective Studies", "descriptor_ui": "D012189", "major_topic": false }, { "descriptor": "Salivary Gland Neoplasms", "descriptor_ui": "D012468", "major_topic": true }, { "descriptor": "Young Adult", "descriptor_ui": "D055815", "major_topic": false } ], "publication": { "conference_name": null, "date": "2024 Nov 19", "date_precision": "day", "issue": "1", "normalized_date": "2024-11-19", "pages": "122", "proceedings_title": null, "publisher": "", "title": "Head and neck pathology", "volume": "18", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "An Institutional Experience of Core Needle Biopsy with Cooperative Implementation by Pathologists and Head and Neck Oncologists in Salivary Gland Carcinoma.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The expectations for artificial intelligence (AI) technology have increased considerably in recent years, mainly due to the emergence of deep learning. At present, AI technology is being used for various purposes and has brought about change in society. In particular, the rapid development of generative AI technology, exemplified by ChatGPT, has amplified the societal impact of AI. The medical field is no exception, with a wide range of AI technologies being introduced for basic and applied research. Further, AI-equipped software as a medical device (AI-SaMD) is also being approved by regulatory bodies. Combined with the advent of big data, data-driven research utilizing AI is actively pursued. Nevertheless, while AI technology has great potential, it also presents many challenges that require careful consideration. In this review, we introduce the current status of AI-based cancer research, especially from the perspective of clinical application, and discuss the associated challenges and future directions, with the aim of helping to promote cancer research that utilizes effective AI technology.", "classifications": [ { "id": "Hamamoto", "label": "Group Hamamoto", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Ryuji", "last_name": "Hamamoto", "name": null }, { "creator_type": "author", "first_name": "Masaaki", "last_name": "Komatsu", "name": null }, { "creator_type": "author", "first_name": "Masayoshi", "last_name": "Yamada", "name": null }, { "creator_type": "author", "first_name": "Kazuma", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Masamichi", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Mototaka", "last_name": "Miyake", "name": null }, { "creator_type": "author", "first_name": "Shunichi", "last_name": "Jinnai", "name": null }, { "creator_type": "author", "first_name": "Takafumi", "last_name": "Koyama", "name": null }, { "creator_type": "author", "first_name": "Nobuji", "last_name": "Kouno", "name": null }, { "creator_type": "author", "first_name": "Hidenori", "last_name": "Machino", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Ken", "last_name": "Asada", "name": null }, { "creator_type": "author", "first_name": "Naonori", "last_name": "Ueda", "name": null }, { "creator_type": "author", "first_name": "Syuzo", "last_name": "Kaneko", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/cas.16395" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "39557634" } }, "mesh": [ { "descriptor": "Artificial Intelligence", "descriptor_ui": "D001185", "major_topic": true }, { "descriptor": "Big Data", "descriptor_ui": "D000077558", "major_topic": false }, { "descriptor": "Biomedical Research", "descriptor_ui": "D035843", "major_topic": true }, { "descriptor": "Deep Learning", "descriptor_ui": "D000077321", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Neoplasms", "descriptor_ui": "D009369", "major_topic": true } ], "publication": { "conference_name": null, "date": "2024 Nov 18", "date_precision": "day", "issue": "", "normalized_date": "2024-11-18", "pages": "", "proceedings_title": null, "publisher": "", "title": "Cancer science", "volume": "", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Current status and future direction of cancer research using artificial intelligence for clinical application.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Objective physical function assessment is crucial for determining patient eligibility for treatment and adjusting the treatment intensity. Existing assessments, such as performance status, are not well standardized, despite their frequent use in daily clinical practice. This paper explored how artificial intelligence (AI) could predict physical function scores from various patient data sources and reviewed methods to measure objective physical function using this technology. This review included relevant articles published in English that were retrieved from PubMed. These studies utilized AI technology to predict physical function indices from patient data extracted from videos, sensors, or electronic health records, thereby eliminating manual measurements. Studies that used AI technology solely to automate traditional evaluations were excluded. These technologies are recommended for future clinical systems that perform repeated objective physical function assessments in all patients without requiring extra time, personnel, or resources. This enables the detection of minimal changes in a patient's condition, enabling early intervention and enhanced outcomes.", "classifications": [ { "id": "Hamamoto", "label": "Group Hamamoto", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Nobuji", "last_name": "Kouno", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Masaaki", "last_name": "Komatsu", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Sakaguchi", "name": null }, { "creator_type": "author", "first_name": "Naoaki", "last_name": "Ishiguro", "name": null }, { "creator_type": "author", "first_name": "Katsuji", "last_name": "Takeda", "name": null }, { "creator_type": "author", "first_name": "Kyoko", "last_name": "Fujioka", "name": null }, { "creator_type": "author", "first_name": "Ayumu", "last_name": "Matsuoka", "name": null }, { "creator_type": "author", "first_name": "Maiko", "last_name": "Fujimori", "name": null }, { "creator_type": "author", "first_name": "Ryuji", "last_name": "Hamamoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.3390/bioengineering11111154" }, "pmcid": { "normalized": "PMC11591743" }, "pmid": { "normalized": "39593814" } }, "mesh": [], "publication": { "conference_name": null, "date": "2024 Nov 16", "date_precision": "day", "issue": "11", "normalized_date": "2024-11-16", "pages": "", "proceedings_title": null, "publisher": "", "title": "Bioengineering (Basel, Switzerland)", "volume": "11", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Introduction of AI Technology for Objective Physical Function Assessment.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "AMIGO2 adheres to liver endothelium and induces liver metastasis. We revealed that genetically altering AMIGO2 expression in tumor cells affects their liver metastatic potential, depending on the AMIGO2 expression level. The aim of this study was to prevent liver metastasis by pharmacologically suppressing AMIGO2 expression. For screening, we used the mouse LV12 cells because of their affinity to adhere to liver endothelium and metastasize the liver owing to elevated AMIGO2 expression. Of the 285 compounds tested, 17 reduced AMIGO2 mRNA expression. We subsequently screened for compounds that inhibited tumor cell adhesion to liver endothelium and identified five compounds that inhibit three signaling pathways (MEK, JAK, and JNK). Treatment with these compounds inhibited liver metastasis of LV12 cells. Next, we used clinically available signal inhibitors (MEK inhibitor trametinib, JAK inhibitor ruxolitinib, and JNK inhibitor SP600125), and found that ruxolitinib inhibits AMIGO2 expression more stably. Furthermore, ruxolitinib inhibited the adhesion of LV12 cells to liver endothelium and suppressed liver metastasis. Using the MKN45 gastric cancer cells, we confirmed that ruxolitinib could prevent liver metastasis of human cancer cells. These results demonstrate that pharmacological inhibition of AMIGO2 expression in tumor cells is a promising novel strategy to prevent and control liver metastasis.", "classifications": [ { "id": "Okamoto", "label": "Group Okamoto", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "HeeKyung", "last_name": "Seong", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Kanda", "name": null }, { "creator_type": "author", "first_name": "Runa", "last_name": "Izutsu", "name": null }, { "creator_type": "author", "first_name": "Jumond P.", "last_name": "Jehung", "name": null }, { "creator_type": "author", "first_name": "Junichi", "last_name": "Hamada", "name": null }, { "creator_type": "author", "first_name": "Mitsuhiko", "last_name": "Osaki", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Okamoto", "name": null }, { "creator_type": "author", "first_name": "Futoshi", "last_name": "Okada", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41598-024-71827-z" }, "pmcid": { "normalized": "PMC11568326" }, "pmid": { "normalized": "39548119" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Anthracenes", "descriptor_ui": "D000873", "major_topic": false }, { "descriptor": "Cell Adhesion", "descriptor_ui": "D002448", "major_topic": true }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Gene Expression Regulation, Neoplastic", "descriptor_ui": "D015972", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Liver Neoplasms", "descriptor_ui": "D008113", "major_topic": true }, { "descriptor": "Membrane Proteins", "descriptor_ui": "D008565", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Nitriles", "descriptor_ui": "D009570", "major_topic": false }, { "descriptor": "Pyrazoles", "descriptor_ui": "D011720", "major_topic": false }, { "descriptor": "Pyridones", "descriptor_ui": "D011728", "major_topic": false }, { "descriptor": "Pyrimidines", "descriptor_ui": "D011743", "major_topic": true }, { "descriptor": "Pyrimidinones", "descriptor_ui": "D011744", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Stomach Neoplasms", "descriptor_ui": "D013274", "major_topic": false } ], "publication": { "conference_name": null, "date": "2024 Nov 15", "date_precision": "day", "issue": "1", "normalized_date": "2024-11-15", "pages": "28183", "proceedings_title": null, "publisher": "", "title": "Scientific reports", "volume": "14", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Prevention of liver metastasis via the pharmacological suppression of AMIGO2 expression in tumor cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Margarine, a water-in-oil (W/O) emulsion, offers advantages such as lower costs in comparison to similar products, but large amounts of saturated fats pose health risks. Reduction of saturated fat content is difficult and often leads to \"oil-off,\" i.e., the seepage of liquid oil from the mixture, resulting in undesirable appearance and texture. Investigations into the phenomenon have often focused on morphology at the water-oil interfaces, and this work establishes Raman imaging as a powerful application for observing microscopic morphologies of W/O emulsions. We analyze morphologies of 5 distinct margarine spreads that differ in manufacturing date, formulation, and manufacturing process. More robust H-bonding in the oil phase of the emulsions co-occurred with smaller amounts of oil-off, suggesting that H-bonding interactions between emulsifier molecules, water, and crystallized fats in the lipid phase of the W/O emulsions results in an emulsion that is less susceptible to the production of oil-off.", "classifications": [ { "id": "Fujita", "label": "Group Fujita", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "J. Nicholas", "last_name": "Taylor", "name": null }, { "creator_type": "author", "first_name": "Kazuki", "last_name": "Bando", "name": null }, { "creator_type": "author", "first_name": "Shiori", "last_name": "Tsukagoshi", "name": null }, { "creator_type": "author", "first_name": "Leo", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Katsumasa", "last_name": "Fujita", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Fujita", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.foodchem.2024.142035" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "39571430" } }, "mesh": [ { "descriptor": "Emulsions", "descriptor_ui": "D004655", "major_topic": true }, { "descriptor": "Hydrogen Bonding", "descriptor_ui": "D006860", "major_topic": true }, { "descriptor": "Machine Learning", "descriptor_ui": "D000069550", "major_topic": true }, { "descriptor": "Margarine", "descriptor_ui": "D008383", "major_topic": true }, { "descriptor": "Spectrum Analysis, Raman", "descriptor_ui": "D013059", "major_topic": true }, { "descriptor": "Water", "descriptor_ui": "D014867", "major_topic": true } ], "publication": { "conference_name": null, "date": "2024 Nov 13", "date_precision": "day", "issue": "Pt 2", "normalized_date": "2024-11-13", "pages": "142035", "proceedings_title": null, "publisher": "", "title": "Food chemistry", "volume": "465", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Microscopic water dispersion and hydrogen-bonding structures in margarine spreads with Raman hyperspectral imaging and machine learning.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The ERK pathway governs essential biological processes such as cell proliferation and survival, and its hyperactivation by various oncogenes ultimately drives carcinogenesis. However, normal mammalian cells typically recognize aberrant ERK signaling as oncogenic stress and respond by inducing cell cycle arrest or apoptosis through activation of the p38 and JNK pathways. Despite the critical role of this response in preventing carcinogenesis, the precise molecular mechanisms underlying oncogene-induced, ERK-dependent activation of p38/JNK and its tumor-suppressive effects remain unclear. Here, we demonstrate that MAP three kinase 1 (MTK1), a stress-responsive MAPKKK, serves as a key mediator of p38/JNK activation induced by oncogenic ERK signaling. Mechanistically, aberrant ERK signaling induces sustained expression of the transcription factor early growth response protein 1 (EGR1), which promotes the production of the MTK1 activator GADD45beta, leading to persistent activation of MTK1-p38/JNK signaling. Gene knockout and transcriptome analyses revealed that this GADD45beta/MTK1-mediated cross-talk between the ERK and p38/JNK pathways preferentially upregulates a specific set of genes involved in apoptosis and the immune response. Notably, the expression of EGR1, GADD45beta, and MTK1 is frequently downregulated in many cancers with high ERK activity, resulting in the disruption of the tumor-suppressive ERK-p38/JNK cross-talk. Restoring GADD45beta expression in cancer cells reactivates p38/JNK signaling and suppresses tumorigenesis. Our findings delineate a molecular mechanism by which normal cells sense and respond to oncogenic stress to prevent abnormal growth, and highlight the significance of its dysregulation in cancer.", "classifications": [ { "id": "JPMJCR2022", "label": "JPMJCR2022", "researcher": "Mutsuhiro Takekawa", "type": "grant" }, { "id": "Takekawa", "label": "Group Takekawa", "parent": "Takekawa", "type": "group" }, { "id": "Takekawa", "label": "Team Takekawa", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Saeko", "last_name": "Kawataki", "name": null }, { "creator_type": "author", "first_name": "Yuji", "last_name": "Kubota", "name": null }, { "creator_type": "author", "first_name": "Kotoe", "last_name": "Katayama", "name": null }, { "creator_type": "author", "first_name": "Seiya", "last_name": "Imoto", "name": null }, { "creator_type": "author", "first_name": "Mutsuhiro", "last_name": "Takekawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/cas.16389" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "39526327" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Antigens, Differentiation", "descriptor_ui": "D000943", "major_topic": false }, { "descriptor": "Apoptosis", "descriptor_ui": "D017209", "major_topic": false }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Cell Proliferation", "descriptor_ui": "D049109", "major_topic": false }, { "descriptor": "Early Growth Response Protein 1", "descriptor_ui": "D051766", "major_topic": true }, { "descriptor": "GADD45 Proteins", "descriptor_ui": "D000097642", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "MAP Kinase Signaling System", "descriptor_ui": "D020935", "major_topic": true }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "p38 Mitogen-Activated Protein Kinases", "descriptor_ui": "D048051", "major_topic": true }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false } ], "publication": { "conference_name": null, "date": "2024 Nov 11", "date_precision": "day", "issue": "", "normalized_date": "2024-11-11", "pages": "", "proceedings_title": null, "publisher": "", "title": "Cancer science", "volume": "", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "GADD45beta-MTK1 signaling axis mediates oncogenic stress-induced activation of the p38 and JNK pathways.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "PURPOSE: To compare the variability of quantitative values from lung adenocarcinoma CT images independently assessed by 2 radiologists and AI-based software under different display conditions, and to identify predictors of pathological lymph node metastasis (LNM), disease-free survival (DFS), and overall survival (OS). METHODS: Preoperative CT images of 307 patients were displayed under 4 conditions: lung-1, lung-2, mediastinum-1, and mediastinum-2. Two radiologists (R1, R2) measured total diameter (tD) and the longest solid diameter (sD) under each condition. The AI-based software automatically detected lung nodules, providing tD, sD, total volume (tV), and solid volume (sV). RESULTS: All measurements by R1 and R2 with AI-based software were identical. Four out of the 8 measurements showed significant variation between R1 and R2. For LNM, multivariate logistic regression identified significant indicators including sD at mediastinum-2 of R1, sD at mediastinum-1 and mediastinum-2 of R2, tV, and the proportion of sV to tV (sV/tV) of AI-based software. For DFS, multivariate Cox regression identified sD at lung-1 of R1, the proportions of sD to tD at lung-2 of R1, sD at lung-2 and mediastinum-1 of R2, tV, and sV/tV of AI-based software as significant. For OS, multivariate Cox regression identified sD at lung-1 and mediastinum-2 of R1, tD at lung-2 of R2, sD at mediastinum-1 of R2, sV, and sV/tV of AI-based software as significant. CONCLUSION: Radiologists' CT measurements were significant predictors of LNM and prognosis, but variability existed among radiologists and display conditions. AI-based software can provide accurate and reproducible indicators for predicting LNM and prognosis.", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Junya", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Yanagawa", "name": null }, { "creator_type": "author", "first_name": "Daiki", "last_name": "Nishigaki", "name": null }, { "creator_type": "author", "first_name": "Akinori", "last_name": "Hata", "name": null }, { "creator_type": "author", "first_name": "Yukinori", "last_name": "Sakao", "name": null }, { "creator_type": "author", "first_name": "Noriaki", "last_name": "Sakakura", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Shintani", "name": null }, { "creator_type": "author", "first_name": "Shoji", "last_name": "Kido", "name": null }, { "creator_type": "author", "first_name": "Noriyuki", "last_name": "Tomiyama", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.cllc.2024.10.015" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "39592291" } }, "mesh": [ { "descriptor": "Adenocarcinoma", "descriptor_ui": "D000230", "major_topic": false }, { "descriptor": "Adenocarcinoma of Lung", "descriptor_ui": "D000077192", "major_topic": true }, { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Aged, 80 and over", "descriptor_ui": "D000369", "major_topic": false }, { "descriptor": "Artificial Intelligence", "descriptor_ui": "D001185", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Lung Neoplasms", "descriptor_ui": "D008175", "major_topic": true }, { "descriptor": "Lymph Nodes", "descriptor_ui": "D008198", "major_topic": false }, { "descriptor": "Lymphatic Metastasis", "descriptor_ui": "D008207", "major_topic": true }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Prognosis", "descriptor_ui": "D011379", "major_topic": false }, { "descriptor": "Radiologists", "descriptor_ui": "D000072177", "major_topic": false }, { "descriptor": "Retrospective Studies", "descriptor_ui": "D012189", "major_topic": false }, { "descriptor": "Software", "descriptor_ui": "D012984", "major_topic": true }, { "descriptor": "Tomography, X-Ray Computed", "descriptor_ui": "D014057", "major_topic": true } ], "publication": { "conference_name": null, "date": "2024 Nov 7", "date_precision": "day", "issue": "", "normalized_date": "2024-11-07", "pages": "S1525-7304(24)00232-8", "proceedings_title": null, "publisher": "", "title": "Clinical lung cancer", "volume": "", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Radiologists Versus AI-Based Software: Predicting Lymph Node Metastasis and Prognosis in Lung Adenocarcinoma From CT Under Various Image Display Conditions.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "SSBD (https://ssbd.riken.jp) is a platform for the sharing and reuse of bioimaging data. As part of efforts to build a bioimaging data ecosystem, SSBD has recently been updated to a two-tiered data resource comprising SSBD:repository, a public repository for the sharing of all types of bioimaging data reported in journals, and SSBD:database, an added-value database for the sharing of curated, highly reusable, metadata-rich data. This update addresses the conflicting demands of rapid data publication and sharing of richly annotated data, thereby promoting bioimaging data sharing and reuse. With this update, SSBD is now positioned as a core repository and database within the foundingGIDE, an international consortium working to establish a global image data ecosystem. Harmonizing metadata between data resources enables cross-searching and data exchange with data resources from other countries and regions.", "classifications": [ { "id": "JPMJCR1926", "label": "JPMJCR1926", "researcher": "Hironobu Fujiwara", "type": "grant" }, { "id": "Fujiwara", "label": "Group Fujiwara", "parent": "Fujiwara", "type": "group" }, { "id": "Onami", "label": "Group Onami", "parent": "Fujiwara", "type": "group" }, { "id": "Fujiwara", "label": "Team Fujiwara", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Koji", "last_name": "Kyoda", "name": null }, { "creator_type": "author", "first_name": "Hiroya", "last_name": "Itoga", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Yamagata", "name": null }, { "creator_type": "author", "first_name": "Emi", "last_name": "Fujisawa", "name": null }, { "creator_type": "author", "first_name": "Fangfang", "last_name": "Wang", "name": null }, { "creator_type": "author", "first_name": "Miguel", "last_name": "Miranda-Miranda", "name": null }, { "creator_type": "author", "first_name": "Haruna", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Yasue", "last_name": "Nakano", "name": null }, { "creator_type": "author", "first_name": "Yukako", "last_name": "Tohsato", "name": null }, { "creator_type": "author", "first_name": "Shuichi", "last_name": "Onami", "name": null } ], "identifiers": { "doi": { "normalized": "10.1093/nar/gkae860" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "39479781" } }, "mesh": [ { "descriptor": "Databases, Factual", "descriptor_ui": "D016208", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Information Dissemination", "descriptor_ui": "D033181", "major_topic": true }, { "descriptor": "Metadata", "descriptor_ui": "D000071253", "major_topic": false }, { "descriptor": "Molecular Imaging", "descriptor_ui": "D057054", "major_topic": false } ], "publication": { "conference_name": null, "date": "2024 Oct 31", "date_precision": "day", "issue": "", "normalized_date": "2024-10-31", "pages": "gkae860", "proceedings_title": null, "publisher": "", "title": "Nucleic acids research", "volume": "", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "SSBD: an ecosystem for enhanced sharing and reuse of bioimaging data.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Hydrogen persulfide (H(2)S(2)) is an important sulfur-containing signaling molecule that plays a crucial role in the homeostasis of various organ systems, such as the renal, cardiovascular, liver, and gastrointestinal systems. However, research on H(2)S(2) in biological settings is still challenging due to its instability and high reactivity. Compounds that can controllably release H(2)S(2) (also known as donors) are thus crucial research tools. Currently, available H(2)S(2) donors are still very limited, with most of them relying on modified disulfide templates. These templates possess an unavoidable limitation of being susceptible to cellular disulfide exchange which can compromise their efficacy. In this work, we explored nondisulfide-based and nonoxidation-dependent templates for the design of H(2)S(2) donors. We found that tertiary naphthacyl thiols could undergo phototriggered C-S homolytic cleavage to form H(2)S(2) via hydrosulfide (HS) radicals. In addition, the release of H(2)S(2) was associated with the formation of a product with strong blue fluorescence, which allowed for real-time monitoring of the release process. This reaction was demonstrated to proceed effectively in both buffers and cells, with the ability to enhance intracellular production of persulfides, including GSSH, CysSSH, H(2)S(2), H(2)S(3), etc. It provides a unique photocontrolled H(2)S(2) donor system with distinct advantages compared to known H(2)S(2) donors due to its good stability and spatiotemporal control ability.", "classifications": [ { "id": "Akaike", "label": "Group Akaike", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Biswajit", "last_name": "Roy", "name": null }, { "creator_type": "author", "first_name": "Meg", "last_name": "Shieh", "name": null }, { "creator_type": "author", "first_name": "Tsuyoshi", "last_name": "Takata", "name": null }, { "creator_type": "author", "first_name": "Minkyung", "last_name": "Jung", "name": null }, { "creator_type": "author", "first_name": "Eshani", "last_name": "Das", "name": null }, { "creator_type": "author", "first_name": "Shi", "last_name": "Xu", "name": null }, { "creator_type": "author", "first_name": "Takaaki", "last_name": "Akaike", "name": null }, { "creator_type": "author", "first_name": "Ming", "last_name": "Xian", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/jacs.4c11540" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "39449660" } }, "mesh": [ { "descriptor": "Free Radicals", "descriptor_ui": "D005609", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Hydrogen Sulfide", "descriptor_ui": "D006862", "major_topic": true }, { "descriptor": "Metabolome", "descriptor_ui": "D055442", "major_topic": false }, { "descriptor": "Sulfhydryl Compounds", "descriptor_ui": "D013438", "major_topic": false }, { "descriptor": "Sulfides", "descriptor_ui": "D013440", "major_topic": true }, { "descriptor": "Sulfur", "descriptor_ui": "D013455", "major_topic": false } ], "publication": { "conference_name": null, "date": "2024 Oct 25", "date_precision": "day", "issue": "", "normalized_date": "2024-10-25", "pages": "", "proceedings_title": null, "publisher": "", "title": "Journal of the American Chemical Society", "volume": "", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Phototriggered Hydrogen Persulfide Donors via Hydrosulfide Radical Formation Enhancing the Reactive Sulfur Metabolome in Cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Background/Objectives: Receptor for hyaluronan-mediated motility (RHAMM) is a hyaluronan (HA) receptor, which exerts diverse biological functions in not only physiological but also pathological conditions in human malignancies, including breast cancer. Although chemoresistance is a significant clinical challenge in breast cancer, a possible contribution of RHAMM and hyaluronan to breast cancer chemoresistance has remained unclear. Methods: We immunolocalized RHAMM and HA in breast carcinoma tissues. Also, we utilized epirubicin-sensitive (parental) and rpirubicin-resistant (EPIR) breast cancer cell lines to explore the role of RHAMMM in breast cancer progression. Results: We found out that RHAMM and HA were cooperatively correlated with breast cancer aggressiveness and recurrence after chemotherapy. In vitro studies demonstrated that RHAMM was overexpressed in EPIR cells compared to parental cells. In addition, the knockdown of RHAMM significantly suppressed proliferation and migration of both parental and EPIR cells. On the other hand, the expression level of cancer stem cell marker CD44, which was overexpressed in M-EPIR (epirubicin-resistant MCF-7 subline) compared to MCF-7, was significantly suppressed by knockdown of RHAMM. In addition, the knockdown of RHAMM significantly altered the expression of N-cadherin and E-cadherin, leading to an epithelial phenotype. Conclusions: Aberrant RHAMM signaling were considered to cause chemoresistance related to cancer stemness and epithelial to mesenchymal transition, and increased cell proliferation and migration of both chemo-sensitive and chemo-resistant breast cancer cells.", "classifications": [ { "id": "Suzuki", "label": "Group Suzuki", "parent": "Takekawa", "type": "group" }, { "id": "Takekawa", "label": "Team Takekawa", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Shiori", "last_name": "Fujisawa", "name": null }, { "creator_type": "author", "first_name": "Kiyoshi", "last_name": "Takagi", "name": null }, { "creator_type": "author", "first_name": "Mio", "last_name": "Yamaguchi-Tanaka", "name": null }, { "creator_type": "author", "first_name": "Ai", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Yasuhiro", "last_name": "Miki", "name": null }, { "creator_type": "author", "first_name": "Minoru", "last_name": "Miyashita", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Tada", "name": null }, { "creator_type": "author", "first_name": "Takanori", "last_name": "Ishida", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Suzuki", "name": null } ], "identifiers": { "doi": { "normalized": "10.3390/cancers16213600" }, "pmcid": { "normalized": "PMC11545538" }, "pmid": { "normalized": "39518040" } }, "mesh": [], "publication": { "conference_name": null, "date": "2024 Oct 25", "date_precision": "day", "issue": "21", "normalized_date": "2024-10-25", "pages": "", "proceedings_title": null, "publisher": "", "title": "Cancers", "volume": "16", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Receptor for Hyaluronan Mediated Motility (RHAMM)/Hyaluronan Axis in Breast Cancer Chemoresistance.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Lung cancer is the leading cause of cancer related deaths worldwide, although some patients with early-stage disease can be cured with surgical resection. Standardised reporting of all clinically relevant pathological parameters is essential for best patient care and is also important for ongoing data collection and refinement of important pathological features that impact patient prognosis, staging and clinical care. Using the established International Collaboration on Cancer Reporting (ICCR) procedure, a representative international expert panel of nine lung pathologists as well as an oncologist was convened. Essential core elements and suggested non-core elements were identified for inclusion in the resected lung cancer pathology data set based on predetermined levels of evidence as well as consensus expert opinion. A lung cancer histopathology reporting guide was developed that includes relevant clinical, macroscopic, microscopic and ancillary testing. Critical review and discussion of current evidence was incorporated into the new data set including changes from the 2021 World Health Organisation (WHO) Classification of Thoracic Tumours, fifth edition, new requirements for grading invasive non-mucinous adenocarcinomas, assessment of response to neoadjuvant therapy and requirements for molecular testing in early-stage resected lung carcinomas. This ICCR data set represents incorporation of all relevant parameters for histology reporting of lung cancer resection specimens. Routine use of this data set is recommended for all pathology reporting of resected lung cancer and it is freely available worldwide on the ICCR website (https://www.iccr-cancer.org/datasets/published-datasets/). Widespread implementation will help to ensure consistent and comprehensive pathology reporting and data collection essential for lung cancer patient care, clinical trials and other research.", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Wendy A.", "last_name": "Cooper", "name": null }, { "creator_type": "author", "first_name": "Fleur", "last_name": "Webster", "name": null }, { "creator_type": "author", "first_name": "Kelly J.", "last_name": "Butnor", "name": null }, { "creator_type": "author", "first_name": "Fiorella", "last_name": "Calabrese", "name": null }, { "creator_type": "author", "first_name": "Teh-Ying", "last_name": "Chou", "name": null }, { "creator_type": "author", "first_name": "David M.", "last_name": "Hwang", "name": null }, { "creator_type": "author", "first_name": "Izidor", "last_name": "Kern", "name": null }, { "creator_type": "author", "first_name": "Sanjay", "last_name": "Popat", "name": null }, { "creator_type": "author", "first_name": "Lynette", "last_name": "Sholl", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null }, { "creator_type": "author", "first_name": "Andrew G.", "last_name": "Nicholson", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/his.15313" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "39438780" } }, "mesh": [ { "descriptor": "Datasets as Topic", "descriptor_ui": "D066264", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Lung Neoplasms", "descriptor_ui": "D008175", "major_topic": true }, { "descriptor": "Pathology, Clinical", "descriptor_ui": "D010338", "major_topic": false } ], "publication": { "conference_name": null, "date": "2024 Oct 22", "date_precision": "day", "issue": "", "normalized_date": "2024-10-22", "pages": "", "proceedings_title": null, "publisher": "", "title": "Histopathology", "volume": "", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Data set for the reporting of lung cancer: recommendations from the International Collaboration on Cancer Reporting (ICCR).", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Liquid droplets, formed by intracellular liquid-liquid phase separation (LLPS), are called membraneless organelles. They provide transient enzymatic reaction fields for maintaining cellular homeostasis, although they might transform into aggregates, leading to neurodegenerative diseases. To understand the nature of intracellular droplets, it is crucial to quantify the liquid droplets inside a living cell as well as to elucidate the underlying biological mechanism. In this study, we performed near-infrared fluorescence and Raman imaging to quantify chemical components inside stress granules (SGs) formed by LLPS in living cells. The Raman images reveal that the nucleic acid concentration inside the SGs was more than 20% higher than the surrounding cytoplasm, whereas the lipid concentration was lower. Quantitative Raman intensity analysis using a water Raman band as an internal standard enables in situ concentration determination of nucleic acids in the SGs and other organelles. The intensity of the biomolecular C-H bands relative to the water band indicates that the crowding environment inside the SGs depends on the stress type; under oxidative stress, the inside of the SGs was nearly identical to the outside, whereas it was sparser in hyperosmotic stressed cells, suggesting that the high concentrations of nucleic acids play a pivotal role in maintaining the environments inside the SGs. These results demonstrate that intracellular droplets are not always highly condensed.", "classifications": [ { "id": "JPMJCR2024", "label": "JPMJCR2024", "researcher": "Motohiro Nishida", "type": "grant" }, { "id": "Nakabayashi", "label": "Group Nakabayashi", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Group Nishida", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Ren", "last_name": "Shibuya", "name": null }, { "creator_type": "author", "first_name": "Shinji", "last_name": "Kajimoto", "name": null }, { "creator_type": "author", "first_name": "Hideyuki", "last_name": "Yaginuma", "name": null }, { "creator_type": "author", "first_name": "Tetsuro", "last_name": "Ariyoshi", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Okada", "name": null }, { "creator_type": "author", "first_name": "Takakazu", "last_name": "Nakabayashi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/acs.analchem.4c01096" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "39405087" } }, "mesh": [ { "descriptor": "HeLa Cells", "descriptor_ui": "D006367", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Nucleic Acids", "descriptor_ui": "D009696", "major_topic": true }, { "descriptor": "Oxidative Stress", "descriptor_ui": "D018384", "major_topic": false }, { "descriptor": "Spectrum Analysis, Raman", "descriptor_ui": "D013059", "major_topic": true }, { "descriptor": "Stress Granules", "descriptor_ui": "D000088162", "major_topic": false } ], "publication": { "conference_name": null, "date": "2024 Oct 15", "date_precision": "day", "issue": "", "normalized_date": "2024-10-15", "pages": "", "proceedings_title": null, "publisher": "", "title": "Analytical chemistry", "volume": "", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Nucleic Acid-Rich Stress Granules Are Not Merely Crowded Condensates: A Quantitative Raman Imaging Study.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Cell-based mechanical models, such as the Cell Vertex Model (CVM), have proven useful for studying the mechanical control of epithelial tissue dynamics. We recently developed a statistical method called image-based parameter inference for formulating CVM model functions and estimating their parameters from image data of epithelial tissues. In this study, we employed Bayesian statistics to improve the utility and flexibility of image-based parameter inference. Tests on synthetic data confirmed that both our non-hierarchical and hierarchical Bayesian models provide accurate estimates of model parameters. By applying this method to Drosophila wings, we demonstrated that the reliability of parameter estimation is closely linked to the mechanical anisotropies present in the tissue. Moreover, we revealed that the cortical elasticity term is dispensable for explaining force-shape correlations in vivo. We anticipate that the flexibility of the Bayesian statistical framework will facilitate the integration of various types of information, thereby contributing to the quantitative dissection of the mechanical control of tissue dynamics.", "classifications": [ { "id": "Ishihara", "label": "Group Ishihara", "parent": "Sawai", "type": "group" }, { "id": "Sawai", "label": "Team Sawai", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Xin", "last_name": "Yan", "name": null }, { "creator_type": "author", "first_name": "Goshi", "last_name": "Ogita", "name": null }, { "creator_type": "author", "first_name": "Shuji", "last_name": "Ishihara", "name": null }, { "creator_type": "author", "first_name": "Kaoru", "last_name": "Sugimura", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.jtbi.2024.111960" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "39395535" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Bayes Theorem", "descriptor_ui": "D001499", "major_topic": true }, { "descriptor": "Biomechanical Phenomena", "descriptor_ui": "D001696", "major_topic": false }, { "descriptor": "Drosophila", "descriptor_ui": "D004330", "major_topic": false }, { "descriptor": "Drosophila melanogaster", "descriptor_ui": "D004331", "major_topic": false }, { "descriptor": "Epithelial Cells", "descriptor_ui": "D004847", "major_topic": false }, { "descriptor": "Epithelium", "descriptor_ui": "D004848", "major_topic": false }, { "descriptor": "Models, Biological", "descriptor_ui": "D008954", "major_topic": true }, { "descriptor": "Wings, Animal", "descriptor_ui": "D014921", "major_topic": false } ], "publication": { "conference_name": null, "date": "2024 Oct 10", "date_precision": "day", "issue": "", "normalized_date": "2024-10-10", "pages": "111960", "proceedings_title": null, "publisher": "", "title": "Journal of theoretical biology", "volume": "", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Bayesian parameter inference for epithelial mechanics.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Cells functioning at a specific zone by clustering according to gene expression are recognized as zonated cells. Here, we demonstrate anatomical and functional zones in the zebrafish heart. The cardiomyocytes (CMs) at the atrioventricular canal between the atrium and ventricle could be grouped into three zones according to the localization of signal-activated CMs: Wnt/beta-catenin signal(+), Bmp signal(+), and Tbx2b(+) zones. Endocardial endothelial cells (ECs) changed their characteristics, penetrated the Wnt/beta-catenin signal(+) CM zone, and became coronary ECs covering the heart. Coronary vessel length was reduced when the Wnt/beta-catenin signal(+) CMs were depleted. Collectively, we demonstrate the importance of anatomical and functional zonation of CMs in the zebrafish heart.", "classifications": [ { "id": "Yamamoto", "label": "Group Yamamoto", "parent": "Toyoshima", "type": "group" }, { "id": "Toyoshima", "label": "Team Toyoshima", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Ayano", "last_name": "Chiba", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Hajime", "last_name": "Fukui", "name": null }, { "creator_type": "author", "first_name": "Moe", "last_name": "Fukumoto", "name": null }, { "creator_type": "author", "first_name": "Manabu", "last_name": "Shirai", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Nakajima", "name": null }, { "creator_type": "author", "first_name": "Naoki", "last_name": "Mochizuki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.devcel.2024.09.012" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "39395410" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "beta Catenin", "descriptor_ui": "D051176", "major_topic": true }, { "descriptor": "Coronary Vessels", "descriptor_ui": "D003331", "major_topic": true }, { "descriptor": "Endothelial Cells", "descriptor_ui": "D042783", "major_topic": false }, { "descriptor": "Gene Expression Regulation, Developmental", "descriptor_ui": "D018507", "major_topic": false }, { "descriptor": "Heart Atria", "descriptor_ui": "D006325", "major_topic": false }, { "descriptor": "Myocytes, Cardiac", "descriptor_ui": "D032383", "major_topic": true }, { "descriptor": "Wnt Signaling Pathway", "descriptor_ui": "D060449", "major_topic": true }, { "descriptor": "Zebrafish", "descriptor_ui": "D015027", "major_topic": true }, { "descriptor": "Zebrafish Proteins", "descriptor_ui": "D029961", "major_topic": true } ], "publication": { "conference_name": null, "date": "2024 Oct 8", "date_precision": "day", "issue": "", "normalized_date": "2024-10-08", "pages": "S1534-5807(24)00540-9", "proceedings_title": null, "publisher": "", "title": "Developmental cell", "volume": "", "year": 2024 }, "ssbd": { "database": [], "repository": [ "ssbd-repos-000435" ] }, "title": "Zonated Wnt/beta-catenin signal-activated cardiomyocytes at the atrioventricular canal promote coronary vessel formation in zebrafish.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Complex organ structures are formed with high reproducibility. To achieve such intricate morphologies, the responsible epithelium undergoes multiple simultaneous shape changes, such as elongation and folding. However, these changes have typically been assessed separately. In this study, we revealed how distinct shape changes are controlled during internal organ morphogenesis. The Drosophila embryonic hindgut undergoes left-right asymmetric rotation and anteroposterior elongation in a tissue-autonomous manner driven by cell sliding and convergent extension, respectively, in the hindgut epithelia. However, the regulation of these processes remains unclear. Through genetic analysis and live imaging, we demonstrated that cell sliding and convergent extension are independently regulated by Myosin1D and E-cadherin, and Par-3, respectively, whereas both require MyosinII activity. Using a mathematical model, we demonstrated that independently regulated cellular dynamics can simultaneously cause shape changes in a single mechanical system using anisotropic edge contraction. Our findings indicate that distinct cellular dynamics sharing a common apparatus can be independently and simultaneously controlled to form complex organ shapes. This suggests that such a mechanism may be a general strategy during complex tissue morphogenesis.", "classifications": [ { "id": "Okuda", "label": "Group Okuda", "parent": "Imayoshi", "type": "group" }, { "id": "Imayoshi", "label": "Team Imayoshi", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Mikiko", "last_name": "Inaki", "name": null }, { "creator_type": "author", "first_name": "Takamasa", "last_name": "Higashi", "name": null }, { "creator_type": "author", "first_name": "Satoru", "last_name": "Okuda", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Matsuno", "name": null } ], "identifiers": { "doi": { "normalized": "10.1371/journal.pgen.1011422" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "39374304" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Body Patterning", "descriptor_ui": "D019521", "major_topic": false }, { "descriptor": "Cadherins", "descriptor_ui": "D015820", "major_topic": true }, { "descriptor": "Drosophila melanogaster", "descriptor_ui": "D004331", "major_topic": true }, { "descriptor": "Drosophila Proteins", "descriptor_ui": "D029721", "major_topic": true }, { "descriptor": "Embryo, Nonmammalian", "descriptor_ui": "D004625", "major_topic": false }, { "descriptor": "Epithelium", "descriptor_ui": "D004848", "major_topic": false }, { "descriptor": "Gene Expression Regulation, Developmental", "descriptor_ui": "D018507", "major_topic": false }, { "descriptor": "Morphogenesis", "descriptor_ui": "D009024", "major_topic": true }, { "descriptor": "Myosin Type II", "descriptor_ui": "D024462", "major_topic": false }, { "descriptor": "Myosins", "descriptor_ui": "D009218", "major_topic": false }, { "descriptor": "Rotation", "descriptor_ui": "D012399", "major_topic": false } ], "publication": { "conference_name": null, "date": "2024 Oct 7", "date_precision": "day", "issue": "10", "normalized_date": "2024-10-07", "pages": "e1011422", "proceedings_title": null, "publisher": "", "title": "PLoS genetics", "volume": "20", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Distinct cellular and junctional dynamics independently regulate the rotation and elongation of the embryonic gut in Drosophila.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Selective vulnerability offers a conceptual framework for understanding neurodegenerative disorders such as Parkinson's disease, where specific neuronal types are selectively affected and adjacent ones are spared. However, the applicability of this framework to neurodevelopmental disorders, particularly those characterized by atypical social behaviors, such as autism spectrum disorder, remains uncertain. Here we show that an embryonic disturbance, known to induce social dysfunction in male mice, preferentially impaired the gene expression crucial for neural functions in parvocellular oxytocin (OT) neurons-a subtype linked to social rewards-while neighboring cell types experienced a lesser impact. Chemogenetic stimulation of OT neurons at the neonatal stage ameliorated social deficits in early adulthood, concurrent with cell-type-specific sustained recovery of pivotal gene expression within parvocellular OT neurons. Collectively, our data shed light on the transcriptomic selective vulnerability within the hypothalamic social behavioral center and provide a potential therapeutic target through specific neonatal neurostimulation.", "classifications": [ { "id": "Miyamichi", "label": "Group Miyamichi", "parent": "Enomoto", "type": "group" }, { "id": "Enomoto", "label": "Team Enomoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Masafumi", "last_name": "Tsurutani", "name": null }, { "creator_type": "author", "first_name": "Teppei", "last_name": "Goto", "name": null }, { "creator_type": "author", "first_name": "Mitsue", "last_name": "Hagihara", "name": null }, { "creator_type": "author", "first_name": "Satsuki", "last_name": "Irie", "name": null }, { "creator_type": "author", "first_name": "Kazunari", "last_name": "Miyamichi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41467-024-53092-w" }, "pmcid": { "normalized": "PMC11456597" }, "pmid": { "normalized": "39370447" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Autism Spectrum Disorder", "descriptor_ui": "D000067877", "major_topic": false }, { "descriptor": "Behavior, Animal", "descriptor_ui": "D001522", "major_topic": false }, { "descriptor": "Disease Models, Animal", "descriptor_ui": "D004195", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Hypothalamus", "descriptor_ui": "D007031", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": true }, { "descriptor": "Oxytocin", "descriptor_ui": "D010121", "major_topic": true }, { "descriptor": "Social Behavior", "descriptor_ui": "D012919", "major_topic": true }, { "descriptor": "Transcriptome", "descriptor_ui": "D059467", "major_topic": false } ], "publication": { "conference_name": null, "date": "2024 Oct 6", "date_precision": "day", "issue": "1", "normalized_date": "2024-10-06", "pages": "8661", "proceedings_title": null, "publisher": "", "title": "Nature communications", "volume": "15", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Selective vulnerability of parvocellular oxytocin neurons in social dysfunction.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Natural products that inhibit osteoclast differentiation are promising therapeutic and preventive agents for osteoporosis. Conventionally, identifying osteoclast differentiation involves visual inspection of the microscope images of stained osteoclasts. In this study, a supervised machine learning model was developed to classify bright-field microscope images of osteoclasts without staining. The model was used to screen a compound library, and osteoclast differentiation inhibitors were identified, demonstrating the validity of our method. Next, an in-house library of fungal extracts was screened, and pinolidoxin was revealed as an inhibitor of osteoclast differentiation. Our machine learning method enabled accurate, objective, and high-throughput evaluation of osteoclast differentiation and efficient screening of the inhibitors from natural product extracts. This study represents the first machine learning classification developed to evaluate the inhibitory activity of natural products in osteoclast differentiation.", "classifications": [ { "id": "Higaki", "label": "Group Higaki", "parent": "Ueda", "type": "group" }, { "id": "Ueda", "label": "Team Ueda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yuki", "last_name": "Hitora", "name": null }, { "creator_type": "author", "first_name": "Mako", "last_name": "Hokaguchi", "name": null }, { "creator_type": "author", "first_name": "Yusaku", "last_name": "Sadahiro", "name": null }, { "creator_type": "author", "first_name": "Takumi", "last_name": "Higaki", "name": null }, { "creator_type": "author", "first_name": "Sachiko", "last_name": "Tsukamoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/acs.jnatprod.4c00640" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "39364554" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Biological Products", "descriptor_ui": "D001688", "major_topic": true }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": true }, { "descriptor": "Machine Learning", "descriptor_ui": "D000069550", "major_topic": true }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Molecular Structure", "descriptor_ui": "D015394", "major_topic": false }, { "descriptor": "Osteoclasts", "descriptor_ui": "D010010", "major_topic": true } ], "publication": { "conference_name": null, "date": "2024 Oct 4", "date_precision": "day", "issue": "", "normalized_date": "2024-10-04", "pages": "", "proceedings_title": null, "publisher": "", "title": "Journal of natural products", "volume": "", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Machine Learning Accelerates Screening of Osteoclast Differentiation Inhibitors from Natural Products.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The reflexive excitation of the sympathetic nervous system in response to psychological stress leads to elevated blood pressure, a condition that persists even after the stress has been alleviated. This sustained increase in blood pressure, which may contribute to the pathophysiology of hypertension, could be linked to neural plasticity in sympathetic nervous activity. Given the critical role of astrocytes in various forms of neural plasticity, we investigated their involvement in maintaining elevated blood pressure during the post-stress phase. Specifically, we examined the effects of arundic acid, an astrocytic inhibitor, on blood pressure and heart rate responses to air-jet stress. First, we confirmed that the inhibitory effect of arundic acid is specific to astrocytes. Using c-Fos immunohistology, we then observed that psychological stress activates neurons in cardiovascular brain regions, and that this stress-induced neuronal activation was suppressed by arundic acid pre-treatment in rats. By evaluating astrocytic process thickness, we also confirmed that astrocytes in the cardiovascular brain regions were activated by stress, and this activation was blocked by arundic acid pre-treatment. Next, we conducted blood pressure measurements on unanesthetized, unrestrained rats. Air-jet stress elevated blood pressure, which remained high for a significant period during the post-stress phase. However, pre-treatment with arundic acid, which inhibited astrocytic activation, suppressed stress-induced blood pressure elevation both during and after stress. In contrast, arundic acid had no significant impact on heart rate. These findings suggest that both neurons and astrocytes play integral roles in stress-induced blood pressure elevation and its persistence after stress, offering new insights into the pathophysiological mechanisms underlying hypertension.", "classifications": [ { "id": "Yokota", "label": "Group Yokota", "parent": "Enomoto", "type": "group" }, { "id": "Enomoto", "label": "Team Enomoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yohei", "last_name": "Hasebe", "name": null }, { "creator_type": "author", "first_name": "Shigefumi", "last_name": "Yokota", "name": null }, { "creator_type": "author", "first_name": "Isato", "last_name": "Fukushi", "name": null }, { "creator_type": "author", "first_name": "Kotaro", "last_name": "Takeda", "name": null }, { "creator_type": "author", "first_name": "Masashi", "last_name": "Yoshizawa", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Onimaru", "name": null }, { "creator_type": "author", "first_name": "Yosuke", "last_name": "Kono", "name": null }, { "creator_type": "author", "first_name": "Shuei", "last_name": "Sugama", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Uchiyama", "name": null }, { "creator_type": "author", "first_name": "Keiichi", "last_name": "Koizumi", "name": null }, { "creator_type": "author", "first_name": "Jouji", "last_name": "Horiuchi", "name": null }, { "creator_type": "author", "first_name": "Yoshihiko", "last_name": "Kakinuma", "name": null }, { "creator_type": "author", "first_name": "Mieczyslaw", "last_name": "Pokorski", "name": null }, { "creator_type": "author", "first_name": "Takako", "last_name": "Toda", "name": null }, { "creator_type": "author", "first_name": "Masahiko", "last_name": "Izumizaki", "name": null }, { "creator_type": "author", "first_name": "Yasuo", "last_name": "Mori", "name": null }, { "creator_type": "author", "first_name": "Kanji", "last_name": "Sugita", "name": null }, { "creator_type": "author", "first_name": "Yasumasa", "last_name": "Okada", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41598-024-73345-4" }, "pmcid": { "normalized": "PMC11450218" }, "pmid": { "normalized": "39363030" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Astrocytes", "descriptor_ui": "D001253", "major_topic": true }, { "descriptor": "Blood Pressure", "descriptor_ui": "D001794", "major_topic": true }, { "descriptor": "Brain", "descriptor_ui": "D001921", "major_topic": false }, { "descriptor": "Heart Rate", "descriptor_ui": "D006339", "major_topic": false }, { "descriptor": "Hypertension", "descriptor_ui": "D006973", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Proto-Oncogene Proteins c-fos", "descriptor_ui": "D016760", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Rats, Sprague-Dawley", "descriptor_ui": "D017207", "major_topic": false }, { "descriptor": "Stress, Psychological", "descriptor_ui": "D013315", "major_topic": true } ], "publication": { "conference_name": null, "date": "2024 Oct 3", "date_precision": "day", "issue": "1", "normalized_date": "2024-10-03", "pages": "22984", "proceedings_title": null, "publisher": "", "title": "Scientific reports", "volume": "14", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Persistence of post-stress blood pressure elevation requires activation of astrocytes.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Accurate estimation of tumor mutational burden (TMB) as a predictor of responsiveness to immune checkpoint inhibitors in gene panel assays requires an adequate panel size. The current calculations of TMB only consider coding regions, while most of gene panel assays interrogate non-coding regions. Leveraging the non-coding regions is a potential solution to address this panel size limitation. However, the impact of including non-coding regions on the accuracy of TMB estimates remains unclear. This study investigated the validity of leveraging non-coding regions to supplement panel size using the OncoGuide NCC Oncopanel System (NOP). The aim of this study was to evaluate test performance against orthogonal assays and the association with responsiveness to immune checkpoint inhibitors was not included in the evaluation. We compared TMB status and values between TMB calculated only from coding regions (NOP-coding) and from both coding and non-coding regions (NOP-overall) using whole exome sequencing (WES) and FoundationOne(R)CDx (F1CDx) assay. Our findings revealed that NOP-overall significantly improved the overall percent agreement (OPA) with TMB status compared with NOP-coding for both WES (OPA: 96.7% vs. 73.3%, n = 30) and F1CDx (OPA: 90.0% vs. 73.3%). Additionally, the mean difference in TMB values compared with WES was lower for NOP-overall (3.55 [95% CI: 0.98-6.13]) than for NOP-coding (6.22 [95% CI: 3.73-8.70]). These results exemplify the utility of incorporating non-coding regions to maintain accurate TMB estimates in small-sized panels.", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Takahiro", "last_name": "Nishino", "name": null }, { "creator_type": "author", "first_name": "Mio", "last_name": "Yumura", "name": null }, { "creator_type": "author", "first_name": "Kuniko", "last_name": "Sunami", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Kubo", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Ichikawa", "name": null }, { "creator_type": "author", "first_name": "Tomoyo", "last_name": "Yasuda", "name": null }, { "creator_type": "author", "first_name": "Eisaku", "last_name": "Furukawa", "name": null }, { "creator_type": "author", "first_name": "Momoko", "last_name": "Nagai", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null }, { "creator_type": "author", "first_name": "Mamoru", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Kohno", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/cas.16342" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "39351646" } }, "mesh": [ { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Biomarkers, Tumor", "descriptor_ui": "D014408", "major_topic": false }, { "descriptor": "Exome Sequencing", "descriptor_ui": "D000073359", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": true }, { "descriptor": "Neoplasms", "descriptor_ui": "D009369", "major_topic": true }, { "descriptor": "Tumor Burden", "descriptor_ui": "D047368", "major_topic": false } ], "publication": { "conference_name": null, "date": "2024 Oct 1", "date_precision": "day", "issue": "", "normalized_date": "2024-10-01", "pages": "", "proceedings_title": null, "publisher": "", "title": "Cancer science", "volume": "", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Leveraging non-coding regions to guarantee the accuracy of small-sized panel-based tumor mutational burden estimates.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Axolotl (Ambystoma mexicanum) limb regeneration begins with blastemas of various sizes, in contrast to the limb developmental process. Despite this size variation, normal limb morphology, consistent with a limb stump size, is regenerated. This outcome suggests the existence of underlying scale-invariant mechanisms. To identify such mechanisms, we examined the allometric relationships between blastema size, and Sonic Hedgehog (Shh) and Fibroblast Growth Factor 8 (Fgf8) expression patterns against limb stump size. We found that all factors showed allometric rather than isometric scaling; specifically, their relative sizes decrease with an increase in limb stump size. However, the ratio of Shh/Fgf8 signaling dominant region was nearly constant, independent of blastema/body size. Furthermore, the relative spatial patterns of cell density and proliferation activity and the relative position of first digit formation were scale-invariant in the summed Shh/Fgf8 crosstalk region. This scale-invariant nature may underlie the morphogenesis of normal limbs from different sizes of blastemas.", "classifications": [ { "id": "Morishita", "label": "Group Morishita", "parent": "Morishita", "type": "group" }, { "id": "Morishita", "label": "Team Morishita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Saya", "last_name": "Furukawa", "name": null }, { "creator_type": "author", "first_name": "Sakiya", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Ayaka", "last_name": "Ohashi", "name": null }, { "creator_type": "author", "first_name": "Yoshihiro", "last_name": "Morishita", "name": null }, { "creator_type": "author", "first_name": "Akira", "last_name": "Satoh", "name": null } ], "identifiers": { "doi": { "normalized": "10.1242/dev.202697" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "39344771" } }, "mesh": [ { "descriptor": "Ambystoma mexicanum", "descriptor_ui": "D000558", "major_topic": true }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Body Patterning", "descriptor_ui": "D019521", "major_topic": true }, { "descriptor": "Cell Proliferation", "descriptor_ui": "D049109", "major_topic": false }, { "descriptor": "Extremities", "descriptor_ui": "D005121", "major_topic": true }, { "descriptor": "Fibroblast Growth Factor 8", "descriptor_ui": "D051524", "major_topic": true }, { "descriptor": "Hedgehog Proteins", "descriptor_ui": "D053823", "major_topic": true }, { "descriptor": "Morphogenesis", "descriptor_ui": "D009024", "major_topic": true }, { "descriptor": "Regeneration", "descriptor_ui": "D012038", "major_topic": true }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false } ], "publication": { "conference_name": null, "date": "2024 Sep 30", "date_precision": "day", "issue": "", "normalized_date": "2024-09-30", "pages": "dev.202697", "proceedings_title": null, "publisher": "", "title": "Development (Cambridge, England)", "volume": "", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Allometry in limb regeneration and scale-invariant patterning as the basis of normal morphogenesis from different sizes of blastemas.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Hepatic glucose metabolism serves dual purposes: maintaining glucose homeostasis and converting glucose into energy sources; however, the underlying mechanisms are unclear. We quantitatively measured liver metabolites, gene expression, and phosphorylated insulin signaling molecules in mice orally administered varying doses of glucose, and constructed a transomic network. Rapid phosphorylation of insulin signaling molecules in response to glucose intake was observed, in contrast to the more gradual changes in gene expression. Glycolytic and gluconeogenic metabolites and expression of genes involved in glucose metabolism including glucose-6-phosphate, G6pc, and Pck1, demonstrated high glucose dose sensitivity. Whereas, glucokinase expression and glycogen accumulation showed low glucose dose sensitivity. During the early phase after glucose intake, metabolic flux was geared towards glucose homeostasis regardless of the glucose dose but shifted towards energy conversion during the late phase at higher glucose doses. Our research provides a comprehensive view of time- and dose-dependent selective glucose metabolism.", "classifications": [ { "id": "JPMJCR2123", "label": "JPMJCR2123", "researcher": "Shinya Kuroda", "type": "grant" }, { "id": "Inaba", "label": "Group Inaba", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Group Kuroda", "parent": "Kuroda", "type": "group" }, { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yifei", "last_name": "Pan", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Hatano", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Ohno", "name": null }, { "creator_type": "author", "first_name": "Keigo", "last_name": "Morita", "name": null }, { "creator_type": "author", "first_name": "Toshiya", "last_name": "Kokaji", "name": null }, { "creator_type": "author", "first_name": "Yunfan", "last_name": "Bai", "name": null }, { "creator_type": "author", "first_name": "Hikaru", "last_name": "Sugimoto", "name": null }, { "creator_type": "author", "first_name": "Riku", "last_name": "Egami", "name": null }, { "creator_type": "author", "first_name": "Akira", "last_name": "Terakawa", "name": null }, { "creator_type": "author", "first_name": "Dongzi", "last_name": "Li", "name": null }, { "creator_type": "author", "first_name": "Saori", "last_name": "Uematsu", "name": null }, { "creator_type": "author", "first_name": "Hideki", "last_name": "Maehara", "name": null }, { "creator_type": "author", "first_name": "Suguru", "last_name": "Fujita", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Inoue", "name": null }, { "creator_type": "author", "first_name": "Yuka", "last_name": "Inaba", "name": null }, { "creator_type": "author", "first_name": "Atsushi J.", "last_name": "Nagano", "name": null }, { "creator_type": "author", "first_name": "Akiyoshi", "last_name": "Hirayama", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Kuroda", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41540-024-00437-2" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "39349490" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Energy Metabolism", "descriptor_ui": "D004734", "major_topic": true }, { "descriptor": "Glucokinase", "descriptor_ui": "D005941", "major_topic": false }, { "descriptor": "Gluconeogenesis", "descriptor_ui": "D005943", "major_topic": false }, { "descriptor": "Glucose", "descriptor_ui": "D005947", "major_topic": true }, { "descriptor": "Glucose-6-Phosphate", "descriptor_ui": "D019298", "major_topic": false }, { "descriptor": "Glycolysis", "descriptor_ui": "D006019", "major_topic": false }, { "descriptor": "Homeostasis", "descriptor_ui": "D006706", "major_topic": true }, { "descriptor": "Insulin", "descriptor_ui": "D007328", "major_topic": false }, { "descriptor": "Liver", "descriptor_ui": "D008099", "major_topic": true }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Phosphorylation", "descriptor_ui": "D010766", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false } ], "publication": { "conference_name": null, "date": "2024 Sep 30", "date_precision": "day", "issue": "1", "normalized_date": "2024-09-30", "pages": "107", "proceedings_title": null, "publisher": "", "title": "NPJ systems biology and applications", "volume": "10", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Time and dose selective glucose metabolism for glucose homeostasis and energy conversion in the liver.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Electrocatalysts which can operate for several years are required to produce hydrogen and commodity chemicals in an environmentally friendly manner. However, designing materials with long operational lifetimes is challenging, due to the lack of a conceptual framework to predict catalytic lifetimes quantitatively. Here, we report a microkinetic equation which quantifies the lifetime of an electrocatalyst undergoing dissolution. This equation was obtained by taking advantage of the fact that catalysis is much faster than deactivation, which allows the ordinary differential equations to be solved via the quasi steady-state approximation. All chemical reactions were modeled as irreversible, first-order elementary reactions. Under this assumption, the catalytic rate correlates linearly with the deactivation rate, leading to a trade-off relationship between activity and stability. Our model was supported by the correlation between theoretical and experimental lifetimes (r(2) = 0.86) of a manganese oxide electrocatalyst during the oxygen evolution reaction.", "classifications": [ { "id": "Mochizuki", "label": "Group Mochizuki", "parent": "Eiraku", "type": "group" }, { "id": "Eiraku", "label": "Team Eiraku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Hideshi", "last_name": "Ooka", "name": null }, { "creator_type": "author", "first_name": "Marie E.", "last_name": "Wintzer", "name": null }, { "creator_type": "author", "first_name": "Hirokazu", "last_name": "Komatsu", "name": null }, { "creator_type": "author", "first_name": "Tomoharu", "last_name": "Suda", "name": null }, { "creator_type": "author", "first_name": "Kiyohiro", "last_name": "Adachi", "name": null }, { "creator_type": "author", "first_name": "Ailong", "last_name": "Li", "name": null }, { "creator_type": "author", "first_name": "Shuang", "last_name": "Kong", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Hashizume", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Mochizuki", "name": null }, { "creator_type": "author", "first_name": "Ryuhei", "last_name": "Nakamura", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/acs.jpclett.4c02162" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "39344961" } }, "mesh": [], "publication": { "conference_name": null, "date": "2024 Sep 30", "date_precision": "day", "issue": "", "normalized_date": "2024-09-30", "pages": "10079-10085", "proceedings_title": null, "publisher": "", "title": "The journal of physical chemistry letters", "volume": "", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Microkinetic Model to Rationalize the Lifetime of Electrocatalysis: Trade-off between Activity and Stability.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Living tissues each exhibit a distinct stiffness, which provides cells with key environmental cues that regulate their behaviors. Despite this significance, our understanding of the spatiotemporal dynamics and the biological roles of stiffness in three-dimensional tissues is currently limited due to a lack of appropriate measurement techniques. To address this issue, we propose a new method combining upright structured illumination microscopy (USIM) and atomic force microscopy (AFM) to obtain precisely coordinated stiffness maps and biomolecular fluorescence images of thick living tissue slices. Using mouse embryonic and adult skin as a representative tissue with mechanically heterogeneous structures inside, we validate the measurement principle of USIM-AFM. Live measurement of tissue stiffness distributions revealed the highly heterogeneous mechanical nature of skin, including nucleated/enucleated epithelium, mesenchyme, and hair follicle, as well as the role of collagens in maintaining its integrity. Furthermore, quantitative analysis comparing stiffness distributions in live tissue samples with those in preserved tissues, including formalin-fixed and cryopreserved tissue samples, unveiled the distinct impacts of preservation processes on tissue stiffness patterns. This series of experiments highlights the importance of live mechanical testing of tissue-scale samples to accurately capture the true spatiotemporal variations in mechanical properties. Our USIM-AFM technique provides a new methodology to reveal the dynamic nature of tissue stiffness and its correlation with biomolecular distributions in live tissues and thus could serve as a technical basis for exploring tissue-scale mechanobiology. STATEMENT OF SIGNIFICANCE: Stiffness, a simple mechanical parameter, has drawn attention in understanding the mechanobiological principles underlying the homeostasis and pathology of living tissues. To explore tissue-scale mechanobiology, we propose a technique integrating an upright structured illumination microscope and an atomic force microscope. This technique enables live measurements of stiffness distribution and fluorescent observation of thick living tissue slices. Experiments revealed the highly heterogeneous mechanical nature of mouse embryonic and adult skin in three dimensions and the previously unnoticed influences of preservation techniques on the mechanical properties of tissue at microscopic resolution. This study provides a new technical platform for live stiffness measurement and biomolecular observation of tissue-scale samples with micron-scale resolution, thus contributing to future studies of tissue- and organ-scale mechanobiology.", "classifications": [ { "id": "JPMJCR1921", "label": "JPMJCR1921", "researcher": "Itaru Imayoshi", "type": "grant" }, { "id": "JPMJCR1926", "label": "JPMJCR1926", "researcher": "Hironobu Fujiwara", "type": "grant" }, { "id": "Fujiwara", "label": "Group Fujiwara", "parent": "Fujiwara", "type": "group" }, { "id": "Imayoshi", "label": "Group Imayoshi", "parent": "Imayoshi", "type": "group" }, { "id": "Okuda", "label": "Group Okuda", "parent": "Imayoshi", "type": "group" }, { "id": "Fujiwara", "label": "Team Fujiwara", "type": "team" }, { "id": "Imayoshi", "label": "Team Imayoshi", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Itsuki", "last_name": "Shioka", "name": null }, { "creator_type": "author", "first_name": "Ritsuko", "last_name": "Morita", "name": null }, { "creator_type": "author", "first_name": "Rei", "last_name": "Yagasaki", "name": null }, { "creator_type": "author", "first_name": "Duligengaowa", "last_name": "Wuergezhen", "name": null }, { "creator_type": "author", "first_name": "Tadahiro", "last_name": "Yamashita", "name": null }, { "creator_type": "author", "first_name": "Hironobu", "last_name": "Fujiwara", "name": null }, { "creator_type": "author", "first_name": "Satoru", "last_name": "Okuda", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.actbio.2024.09.023" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "39379233" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Biomechanical Phenomena", "descriptor_ui": "D001696", "major_topic": false }, { "descriptor": "Imaging, Three-Dimensional", "descriptor_ui": "D021621", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Microscopy, Atomic Force", "descriptor_ui": "D018625", "major_topic": true }, { "descriptor": "Skin", "descriptor_ui": "D012867", "major_topic": true } ], "publication": { "conference_name": null, "date": "2024 Sep 27", "date_precision": "day", "issue": "", "normalized_date": "2024-09-27", "pages": "S1742-7061(24)00539-7", "proceedings_title": null, "publisher": "", "title": "Acta biomaterialia", "volume": "", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Ex vivo SIM-AFM measurements reveal the spatial correlation of stiffness and molecular distributions in 3D living tissue.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "During the COVID-19 pandemic, diabetic and obese patients experienced higher rates of hospital admissions, severe illness, and mortality. However, vaccinations failed to provide those vulnerable populations the same level of protection against COVID-19 severity as those without diabetic and obese phenotypes. Our study aimed to investigate how diabetes mellitus (DM) impacts the immune response following vaccination including the artificially designed trimeric SARS-CoV-2 spike (S)-protein. By using two diabetic mouse models, ob/ob mice (obese, hyperglycemic, and insulin-resistant) and STZ-treated mice (insulin-deficient and hyperglycemic), we observed a significant reduction in S-protein-specific IgG antibody titer post-vaccination in both diabetic models compared to wild-type (WT) mice. Both diabetic mouse models exhibited significant abnormalities in spleen tissue, including marked reductions in splenic weight and the size of the white pulp regions. Furthermore, the splenic T-cell and B-cell zones were notably diminished, suggesting an underlying immune dysfunction that could contribute to impaired antibody production. Notably, vaccination with the S-protein, when paired with an optimal adjuvant, did not exacerbate diabetic cardiomyopathy, blood glucose levels, or liver function, providing reassurance about the vaccine's safety. These findings offer valuable insights into potential mechanisms responsible for the decreased persistence of antibody production in diabetic patients.", "classifications": [ { "id": "JPMJCR2024", "label": "JPMJCR2024", "researcher": "Motohiro Nishida", "type": "grant" }, { "id": "Nishida", "label": "Group Nishida", "parent": "Nishida", "type": "group" }, { "id": "Nishimura", "label": "Group Nishimura", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yara", "last_name": "Atef", "name": null }, { "creator_type": "author", "first_name": "Tomoya", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Akitsu", "last_name": "Masuda", "name": null }, { "creator_type": "author", "first_name": "Yuri", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Akiyuki", "last_name": "Nishimura", "name": null }, { "creator_type": "author", "first_name": "Yasunari", "last_name": "Kanda", "name": null }, { "creator_type": "author", "first_name": "Jun", "last_name": "Kunisawa", "name": null }, { "creator_type": "author", "first_name": "Takahiro", "last_name": "Kusakabe", "name": null }, { "creator_type": "author", "first_name": "Motohiro", "last_name": "Nishida", "name": null } ], "identifiers": { "doi": { "normalized": "10.3390/ijms251910379" }, "pmcid": { "normalized": "PMC11476529" }, "pmid": { "normalized": "39408710" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Antibodies, Viral", "descriptor_ui": "D000914", "major_topic": true }, { "descriptor": "Antibody Formation", "descriptor_ui": "D000917", "major_topic": false }, { "descriptor": "COVID-19", "descriptor_ui": "D000086382", "major_topic": true }, { "descriptor": "COVID-19 Vaccines", "descriptor_ui": "D000086663", "major_topic": true }, { "descriptor": "Diabetes Mellitus, Experimental", "descriptor_ui": "D003921", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Immunoglobulin G", "descriptor_ui": "D007074", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Obese", "descriptor_ui": "D008820", "major_topic": false }, { "descriptor": "SARS-CoV-2", "descriptor_ui": "D000086402", "major_topic": true }, { "descriptor": "Spike Glycoprotein, Coronavirus", "descriptor_ui": "D064370", "major_topic": true }, { "descriptor": "Spleen", "descriptor_ui": "D013154", "major_topic": true } ], "publication": { "conference_name": null, "date": "2024 Sep 26", "date_precision": "day", "issue": "19", "normalized_date": "2024-09-26", "pages": "", "proceedings_title": null, "publisher": "", "title": "International journal of molecular sciences", "volume": "25", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Diabetic Mice Spleen Vulnerability Contributes to Decreased Persistence of Antibody Production after SARS-CoV-2 Vaccine.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "PATOL1 contributes to increasing biomass not only by effective stomatal movement but also by root meristematic activity. PATROL1 (PROTON ATPase TRANSLOCATION CONTROL 1), a protein with a MUN domain, is involved in the intercellular trafficking of AHA1 H(+)-ATPase to the plasma membrane in guard cells. This allows for larger stomatal opening and more efficient photosynthesis, leading to increased biomass. Although PATROL1 is expressed not only in stomata but also in other tissues of the shoot and root, the role in other tissues than stomata has not been determined yet. Here, we investigated PATROL1 functions in roots using a loss-of-function mutant and an overexpressor. Cytological observations revealed that root meristematic size was significantly smaller in the mutant resulting in the short primary root. Grafting experiments showed that the shoot biomass of the mutant scion was increased when it grafted onto wild-type or overexpressor rootstocks. Conversely, grafting of the overexpressor scion shoot enhanced the growth of the mutant rootstock. The leaf temperatures of the grafted plants were consistent with those of their respective genotypes, indicating cell-autonomous behavior of stomatal movement and independent roles of PATROL1 in plant growth. Moreover, plasma membrane localization of AHA1 was not altered in root epidermal cells in the patrol1 mutant implying existence of a different mode of PATROL1 action in roots. Thus PATROL1 plays a role in root meristem and contributes to increase shoot biomass.", "classifications": [ { "id": "JPMJCR2121", "label": "JPMJCR2121", "researcher": "Minako Ueda", "type": "grant" }, { "id": "Higaki", "label": "Group Higaki", "parent": "Ueda", "type": "group" }, { "id": "Ueda", "label": "Group Ueda", "parent": "Ueda", "type": "group" }, { "id": "Ueda", "label": "Team Ueda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Michitaka", "last_name": "Notaguchi", "name": null }, { "creator_type": "author", "first_name": "Manami", "last_name": "Ichita", "name": null }, { "creator_type": "author", "first_name": "Takaya", "last_name": "Kawasoe", "name": null }, { "creator_type": "author", "first_name": "Keina", "last_name": "Monda", "name": null }, { "creator_type": "author", "first_name": "Ken-Ichi", "last_name": "Kurotani", "name": null }, { "creator_type": "author", "first_name": "Takumi", "last_name": "Higaki", "name": null }, { "creator_type": "author", "first_name": "Koh", "last_name": "Iba", "name": null }, { "creator_type": "author", "first_name": "Mimi", "last_name": "Hashimoto-Sugimoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/s00425-024-04526-8" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "39325207" } }, "mesh": [ { "descriptor": "Arabidopsis", "descriptor_ui": "D017360", "major_topic": true }, { "descriptor": "Arabidopsis Proteins", "descriptor_ui": "D029681", "major_topic": true }, { "descriptor": "Biomass", "descriptor_ui": "D018533", "major_topic": true }, { "descriptor": "Cell Membrane", "descriptor_ui": "D002462", "major_topic": false }, { "descriptor": "Gene Expression Regulation, Plant", "descriptor_ui": "D018506", "major_topic": false }, { "descriptor": "Meristem", "descriptor_ui": "D018519", "major_topic": false }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": false }, { "descriptor": "Plant Leaves", "descriptor_ui": "D018515", "major_topic": false }, { "descriptor": "Plant Roots", "descriptor_ui": "D018517", "major_topic": true }, { "descriptor": "Plant Shoots", "descriptor_ui": "D018520", "major_topic": true }, { "descriptor": "Plant Stomata", "descriptor_ui": "D054046", "major_topic": false }, { "descriptor": "Proton-Translocating ATPases", "descriptor_ui": "D006180", "major_topic": false } ], "publication": { "conference_name": null, "date": "2024 Sep 26", "date_precision": "day", "issue": "5", "normalized_date": "2024-09-26", "pages": "105", "proceedings_title": null, "publisher": "", "title": "Planta", "volume": "260", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "The PATROL1 function in roots contributes to the increase in shoot biomass.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "AIMS: The PEComa family of tumours is defined by spindle/epithelioid cells with myomelanocytic differentiation. A small subset harbours TFE3 fusion; however, YAP1::TEE3 has not been reported. Clear cell stromal tumour of the lung (CCST-L) is an emerging entity characterized by spindle to epithelioid cells with focal cytoplasmic clearing, inflammatory infiltrates, no myomelanocytic differentiation, and YAP1::TFE3 fusion. Herein, we report two cases of lung tumours with myomelanocytic differentiation that showed inflammatory spindle cell histology, focal epithelioid clear cells, as well as YAP1::TFE3 fusion. METHODS AND RESULTS: The patients were both men, aged 61 and 68 years. The tumours in both cases presented as well-circumscribed solid masses involving the lung hilum. After lobectomy, no recurrence was observed at 7 and 32 months. Both tumours shared storiform to short fascicular growth of long spindle cells, with a minor component of epithelioid cells showing clear cytoplasm in the background of substantial intratumoral chronic inflammation and dilated blood vessels. One tumour showed focal melanin deposition. Both tumours were immunohistochemically positive for HMB45, Melan A, and h-caldesmon. Fluorescence in situ hybridization assays indicated the presence of YAP1::TFE3 fusions, which was confirmed by RNA sequencing in one case tested, and by immunohistochemical TFE3 expression and loss of YAP1 C-terminus staining. CONCLUSION: We present two cases of inflammatory spindle to epithelioid cell tumours of the lungs with myomelanocytic differentiation and YAP1::TFE3 fusion. This unique morphology and gene fusion suggest that these tumours may constitute a distinct subset of lung PEComa. Furthermore, morphological and molecular overlap with CCST-L gives rise to a hypothesis of a potential inherent relationship between PEComa and CCST-L.", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Naoki", "last_name": "Kojima", "name": null }, { "creator_type": "author", "first_name": "Shogo", "last_name": "Nishino", "name": null }, { "creator_type": "author", "first_name": "Yukiko", "last_name": "Sasahara", "name": null }, { "creator_type": "author", "first_name": "Tetsuro", "last_name": "Taki", "name": null }, { "creator_type": "author", "first_name": "Hiroki", "last_name": "Imada", "name": null }, { "creator_type": "author", "first_name": "Tomohiro", "last_name": "Miyoshi", "name": null }, { "creator_type": "author", "first_name": "Shun-Ichi", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Genichiro", "last_name": "Ishii", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null }, { "creator_type": "author", "first_name": "Taisuke", "last_name": "Mori", "name": null }, { "creator_type": "author", "first_name": "Akihiko", "last_name": "Yoshida", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/his.15328" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "39327855" } }, "mesh": [ { "descriptor": "Adaptor Proteins, Signal Transducing", "descriptor_ui": "D048868", "major_topic": false }, { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Basic Helix-Loop-Helix Leucine Zipper Transcription Factors", "descriptor_ui": "D051778", "major_topic": true }, { "descriptor": "Biomarkers, Tumor", "descriptor_ui": "D014408", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Lung Neoplasms", "descriptor_ui": "D008175", "major_topic": true }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Oncogene Proteins, Fusion", "descriptor_ui": "D015514", "major_topic": false }, { "descriptor": "Perivascular Epithelioid Cell Neoplasms", "descriptor_ui": "D054973", "major_topic": true }, { "descriptor": "Transcription Factors", "descriptor_ui": "D014157", "major_topic": true }, { "descriptor": "YAP-Signaling Proteins", "descriptor_ui": "D000091102", "major_topic": true } ], "publication": { "conference_name": null, "date": "2024 Sep 26", "date_precision": "day", "issue": "", "normalized_date": "2024-09-26", "pages": "", "proceedings_title": null, "publisher": "", "title": "Histopathology", "volume": "", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Inflammatory spindle cell PEComa of the lung with YAP1::TFE3 fusion: a report of two cases and a potential relationship with clear cell stromal tumour.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Inter-kingdom communication through small molecules is essential to the coexistence of organisms in an ecosystem. In soil communities, the plant root is a nexus of interactions for a remarkable number of fungi and is a source of small-molecule plant hormones that shape fungal compositions. Although hormone signaling pathways are established in plants, how fungi perceive and respond to molecules is unclear because many plant-associated fungi are recalcitrant to experimentation. Here, we develop an approach using the model fungus, Saccharomyces cerevisiae, to elucidate mechanisms of fungal response to plant hormones. Two plant hormones, strigolactone and methyl jasmonate, produce unique transcript profiles in yeast, affecting phosphate and sugar metabolism, respectively. Genetic analysis in combination with structural studies suggests that SLs require the high-affinity transporter Pho84 to modulate phosphate homeostasis. The ability to study small-molecule plant hormones in a tractable genetic system should have utility in understanding fungal-plant interactions.", "classifications": [ { "id": "JPMJCR1924", "label": "JPMJCR1924", "researcher": "Yuichiro Tsuchiya", "type": "grant" }, { "id": "Tsuchiya", "label": "Group Tsuchiya", "parent": "Tsuchiya", "type": "group" }, { "id": "Tsuchiya", "label": "Team Tsuchiya", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "James M.", "last_name": "Bradley", "name": null }, { "creator_type": "author", "first_name": "Michael", "last_name": "Bunsick", "name": null }, { "creator_type": "author", "first_name": "George", "last_name": "Ly", "name": null }, { "creator_type": "author", "first_name": "Bruno", "last_name": "Aquino", "name": null }, { "creator_type": "author", "first_name": "Flora Zhiqi", "last_name": "Wang", "name": null }, { "creator_type": "author", "first_name": "Duncan", "last_name": "Holbrook-Smith", "name": null }, { "creator_type": "author", "first_name": "Shingo", "last_name": "Suginoo", "name": null }, { "creator_type": "author", "first_name": "Dylan", "last_name": "Bradizza", "name": null }, { "creator_type": "author", "first_name": "Naoki", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Omar", "last_name": "As'sadiq", "name": null }, { "creator_type": "author", "first_name": "Nina", "last_name": "Marsh", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Osada", "name": null }, { "creator_type": "author", "first_name": "Francois-Didier", "last_name": "Boyer", "name": null }, { "creator_type": "author", "first_name": "Christopher S. P.", "last_name": "McErlean", "name": null }, { "creator_type": "author", "first_name": "Yuichiro", "last_name": "Tsuchiya", "name": null }, { "creator_type": "author", "first_name": "Rajagopal", "last_name": "Subramaniam", "name": null }, { "creator_type": "author", "first_name": "Dario", "last_name": "Bonetta", "name": null }, { "creator_type": "author", "first_name": "Peter", "last_name": "McCourt", "name": null }, { "creator_type": "author", "first_name": "Shelley", "last_name": "Lumba", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.molcel.2024.09.004" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "39357514" } }, "mesh": [ { "descriptor": "Acetates", "descriptor_ui": "D000085", "major_topic": false }, { "descriptor": "Cyclopentanes", "descriptor_ui": "D003517", "major_topic": true }, { "descriptor": "Gene Expression Regulation, Fungal", "descriptor_ui": "D015966", "major_topic": false }, { "descriptor": "Heterocyclic Compounds, 3-Ring", "descriptor_ui": "D006575", "major_topic": false }, { "descriptor": "Homeostasis", "descriptor_ui": "D006706", "major_topic": true }, { "descriptor": "Lactones", "descriptor_ui": "D007783", "major_topic": true }, { "descriptor": "Models, Molecular", "descriptor_ui": "D008958", "major_topic": false }, { "descriptor": "Oxylipins", "descriptor_ui": "D054883", "major_topic": true }, { "descriptor": "Phosphates", "descriptor_ui": "D010710", "major_topic": true }, { "descriptor": "Plant Growth Regulators", "descriptor_ui": "D010937", "major_topic": true }, { "descriptor": "Proton-Phosphate Symporters", "descriptor_ui": "D028081", "major_topic": false }, { "descriptor": "Saccharomyces cerevisiae", "descriptor_ui": "D012441", "major_topic": true }, { "descriptor": "Saccharomyces cerevisiae Proteins", "descriptor_ui": "D029701", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false } ], "publication": { "conference_name": null, "date": "2024 Sep 25", "date_precision": "day", "issue": "", "normalized_date": "2024-09-25", "pages": "S1097-2765(24)00737-8", "proceedings_title": null, "publisher": "", "title": "Molecular cell", "volume": "", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Modulation of fungal phosphate homeostasis by the plant hormone strigolactone.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "I. BACKGROUND: Human induced pluripotent stem cell (hiPSC) derived cardiomyocytes (CMs) have been utilized in drug toxicity evaluation, drug discovery, and treating heart failure patients, showing substantial effects. Ensuring the quality, purity, and maturation of hiPSC-CMs during large-scale production is crucial. There is a growing demand for a novel method to characterize cell molecular profiles without labels and without causing damage. II. METHODS: In this study, we employed label-free Raman microscopy to evaluate hiPSC-derived CMs. The study involved the characterization of cell molecular profiles without labels and without causing damage. The correlation between Raman spectroscopy of specific components, such as cytochrome c and myoglobin, and CM purity and maturation following hiPSC differentiation was investigated. Additionally, the validation of this correlation was performed by assessing mixtures of commercially available CMs (iCell cardiomyocytes2) and fibroblasts at various ratios as well as hiPSC-derived CMs with different efficiencies. Furthermore, CMs were matured using rapid pacing of traveling waves, and the Raman profiles of matured CMs were compared to those of immature ones. III. RESULTS: Raman spectroscopy indicated that the cytochrome c and myoglobin showed correlation with the purity and maturation of CMs following differentiation of hiPSCs. This correlation was validated through experiments involving different CM-fibroblast mixtures and hiPSC-derived CMs with varying efficiencies. Moreover, matured CMs exhibited markedly different Raman profiles compared to immature ones, indicating the potential of Raman imaging as a tool for assessing CM maturation. IV. CONCLUSIONS: We discovered that Raman spectroscopy of certain components, such as cytochrome c and myoglobin, correlates with the CM purity and maturation following hiPSC differentiation. The findings of this study highlight the potential of label-free Raman microscopy as a nondestructive, high-content, and time-efficient method for quality control of hiPSC-derived CMs. This approach could significantly contribute to ensuring the quality and maturity of hiPSC-CMs for various applications in drug discovery and regenerative medicine.", "classifications": [ { "id": "Fujita", "label": "Group Fujita", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Junjun", "last_name": "Li", "name": null }, { "creator_type": "author", "first_name": "Menglu", "last_name": "Li", "name": null }, { "creator_type": "author", "first_name": "Yasunori", "last_name": "Nawa", "name": null }, { "creator_type": "author", "first_name": "Yuting", "last_name": "Liu", "name": null }, { "creator_type": "author", "first_name": "Kazuki", "last_name": "Bando", "name": null }, { "creator_type": "author", "first_name": "Ying", "last_name": "Hua", "name": null }, { "creator_type": "author", "first_name": "Lifu", "last_name": "Sun", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Fujita", "name": null }, { "creator_type": "author", "first_name": "Yoshiki", "last_name": "Sawa", "name": null }, { "creator_type": "author", "first_name": "Katsumasa", "last_name": "Fujita", "name": null }, { "creator_type": "author", "first_name": "Li", "last_name": "Liu", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/acs.analchem.4c03871" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "39291743" } }, "mesh": [ { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": true }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Cytochromes c", "descriptor_ui": "D045304", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Induced Pluripotent Stem Cells", "descriptor_ui": "D057026", "major_topic": true }, { "descriptor": "Myocytes, Cardiac", "descriptor_ui": "D032383", "major_topic": true }, { "descriptor": "Myoglobin", "descriptor_ui": "D009211", "major_topic": false }, { "descriptor": "Spectrum Analysis, Raman", "descriptor_ui": "D013059", "major_topic": true } ], "publication": { "conference_name": null, "date": "2024 Sep 18", "date_precision": "day", "issue": "", "normalized_date": "2024-09-18", "pages": "", "proceedings_title": null, "publisher": "", "title": "Analytical chemistry", "volume": "", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Label-Free Raman Spectroscopy for Assessing Purity and Maturation of hiPSC-Derived Cardiac Tissue.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Within the same species, individuals exhibiting faster growth tend to have shorter lifespans, even if their fast growth arises from early-life pharmacological interventions. However, in vertebrates, the impact of the early-life environment on the growth rate and lifespan has not been fully elucidated. In this study, by utilizing the short-lived African turquoise killifish, which is suitable for a comprehensive life-stage analysis in a brief timeframe, we explored the effects of housing density during the juvenile stage on holistic life traits. As a result, we found that lower housing densities resulted in faster growth, but led to longer adult lifespan, which was contrary to the common notion. Furthermore, the single-housed adult fish displayed a longer egg-laying period than did their group-housed counterparts. Our transcriptome analysis also demonstrated that, in terms of internal transcriptional programs, the life stage progression and aging process of single-housed fish were slower than those of group-housed fish. Collectively, our results suggest that sharing housing with others in early life might influence whole-life attributes, potentially leading to specific life history traits beyond the typical relationship between the growth rate and lifespan.", "classifications": [ { "id": "Yamamoto", "label": "Group Yamamoto", "parent": "Toyoshima", "type": "group" }, { "id": "Toyoshima", "label": "Team Toyoshima", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Chika", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Emiko", "last_name": "Okabe", "name": null }, { "creator_type": "author", "first_name": "Masanori", "last_name": "Nono", "name": null }, { "creator_type": "author", "first_name": "Saya", "last_name": "Kishimoto", "name": null }, { "creator_type": "author", "first_name": "Hideaki", "last_name": "Matsui", "name": null }, { "creator_type": "author", "first_name": "Tohru", "last_name": "Ishitani", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Masaharu", "last_name": "Uno", "name": null }, { "creator_type": "author", "first_name": "Eisuke", "last_name": "Nishida", "name": null } ], "identifiers": { "doi": { "normalized": "10.18632/aging.206111" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "39302208" } }, "mesh": [ { "descriptor": "Aging", "descriptor_ui": "D000375", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Fundulidae", "descriptor_ui": "D023781", "major_topic": true }, { "descriptor": "Housing, Animal", "descriptor_ui": "D006799", "major_topic": false }, { "descriptor": "Killifishes", "descriptor_ui": "D007695", "major_topic": false }, { "descriptor": "Longevity", "descriptor_ui": "D008136", "major_topic": true }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false } ], "publication": { "conference_name": null, "date": "2024 Sep 16", "date_precision": "day", "issue": "", "normalized_date": "2024-09-16", "pages": "", "proceedings_title": null, "publisher": "", "title": "Aging", "volume": "16", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Single housing of juveniles accelerates early-stage growth but extends adult lifespan in African turquoise killifish.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Plants develop along apical-basal and radial axes. In Arabidopsis thaliana, the radial axis becomes evident when the cells of the 8-cell proembryo divide periclinally, forming inner and outer cell layers. Although changes in cell polarity or morphology likely precede this oriented cell division, the initial events and the factors regulating radial axis formation remain elusive. Here, we report that three transcription factors belonging to the class IV homeodomain-leucine zipper (HD-ZIP IV) family redundantly regulate radial pattern formation: HOMEODOMAIN GLABROUS11 (HDG11), HDG12, and PROTODERMAL FACTOR2 (PDF2). The hdg11 hdg12 pdf2 triple mutant failed to undergo periclinal division at the 8-cell stage and cell differentiation along the radial axis. Live-cell imaging revealed that the mutant defect is already evident in the behavior of the embryo's initial cell (apical cell), which is generated by zygote division. In the wild type, the apical cell grows longitudinally and then radially, and its nucleus remains at the bottom of the cell, where the vertical cell plate emerges. By contrast, the mutant apical cell elongates longitudinally, and its nucleus releases from its basal position, resulting in a transverse division. Computer simulations based on the live-cell imaging data confirmed the importance of the geometric rule (the minimal plane principle and nucleus-passing principle) in determining the cell division plane. We propose that HDG11, HDG12, and PDF2 promote apical cell polarization, i.e., radial cell growth and basal nuclear retention, and set proper radial axis formation during embryogenesis.", "classifications": [ { "id": "JPMJCR2121", "label": "JPMJCR2121", "researcher": "Minako Ueda", "type": "grant" }, { "id": "Higaki", "label": "Group Higaki", "parent": "Ueda", "type": "group" }, { "id": "Ueda", "label": "Group Ueda", "parent": "Ueda", "type": "group" }, { "id": "Ueda", "label": "Team Ueda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Sayuri", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Yuuki", "last_name": "Matsushita", "name": null }, { "creator_type": "author", "first_name": "Yuga", "last_name": "Hanaki", "name": null }, { "creator_type": "author", "first_name": "Takumi", "last_name": "Higaki", "name": null }, { "creator_type": "author", "first_name": "Naoya", "last_name": "Kamamoto", "name": null }, { "creator_type": "author", "first_name": "Katsuyoshi", "last_name": "Matsushita", "name": null }, { "creator_type": "author", "first_name": "Tetsuya", "last_name": "Higashiyama", "name": null }, { "creator_type": "author", "first_name": "Koichi", "last_name": "Fujimoto", "name": null }, { "creator_type": "author", "first_name": "Minako", "last_name": "Ueda", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.cub.2024.08.038" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "39303713" } }, "mesh": [ { "descriptor": "Arabidopsis", "descriptor_ui": "D017360", "major_topic": true }, { "descriptor": "Arabidopsis Proteins", "descriptor_ui": "D029681", "major_topic": true }, { "descriptor": "Cell Polarity", "descriptor_ui": "D016764", "major_topic": true }, { "descriptor": "Gene Expression Regulation, Plant", "descriptor_ui": "D018506", "major_topic": false }, { "descriptor": "Homeodomain Proteins", "descriptor_ui": "D018398", "major_topic": true }, { "descriptor": "Seeds", "descriptor_ui": "D012639", "major_topic": false }, { "descriptor": "Transcription Factors", "descriptor_ui": "D014157", "major_topic": false } ], "publication": { "conference_name": null, "date": "2024 Sep 15", "date_precision": "day", "issue": "", "normalized_date": "2024-09-15", "pages": "S0960-9822(24)01153-9", "proceedings_title": null, "publisher": "", "title": "Current biology : CB", "volume": "", "year": 2024 }, "ssbd": { "database": [ "ssbd-database-000460" ], "repository": [ "ssbd-repos-000460" ] }, "title": "HD-ZIP IV genes are essential for embryo initial cell polarization and the radial axis formation in Arabidopsis.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Ikeuchi", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Matsuno", "name": null }, { "creator_type": "author", "first_name": "Rika", "last_name": "Kusumoto-Matsuo", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Kojima", "name": null }, { "creator_type": "author", "first_name": "Toshihide", "last_name": "Ueno", "name": null }, { "creator_type": "author", "first_name": "Masachika", "last_name": "Ikegami", "name": null }, { "creator_type": "author", "first_name": "Rina", "last_name": "Kitada", "name": null }, { "creator_type": "author", "first_name": "Hitomi", "last_name": "Sumiyoshi-Okuma", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Kojima", "name": null }, { "creator_type": "author", "first_name": "Kan", "last_name": "Yonemori", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null }, { "creator_type": "author", "first_name": "Kazuya", "last_name": "Takamochi", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Ken-Ichi", "last_name": "Yoshioka", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Mano", "name": null }, { "creator_type": "author", "first_name": "Shinji", "last_name": "Kohsaka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41388-024-03159-1" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "39271966" } }, "mesh": [], "publication": { "conference_name": null, "date": "2024 Sep 13", "date_precision": "day", "issue": "", "normalized_date": "2024-09-13", "pages": "", "proceedings_title": null, "publisher": "", "title": "Oncogene", "volume": "", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Correction: GLI1 confers resistance to PARP inhibitors by activating the DNA damage repair pathway.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Wound healing of partially incised Arabidopsis inflorescence stems constitutes cell proliferation that initiates mainly in pith tissues about three days after incision, and that the healing process completes in about seven days. Although the initiation mechanisms of cell proliferation have been well documented, the suppression mechanisms remain elusive. Matrix metalloproteinases (MMPs) are zinc-dependent endopeptidases well-known as proteolytic enzymes in animal systems functioning in extracellular matrix remodeling during physiological and pathological processes, including tissue differentiation, growth, defense, wound healing, and control of cancer growth. In this study, we report At2-MMP might contribute to the suppression mechanism of cell proliferation during tissue-repair process of incised inflorescence stems. At2-MMP transcript was gradually upregulated from day 0 to 5 after incision, and slightly decreased on day 7. Morphological analysis of incised stem of defected mutant at2-mmp revealed significantly enhanced cell proliferation around the incision site. Consistent with this, semi-quantitative analysis of dividing cells displayed a significant increment in the number of dividing cells in at2-mmp as compared to WT. These results showed that the upregulation of At2-MMP at the later stage of wound-healing process is likely to be involved in the completion of the process by attenuating the cell proliferation.", "classifications": [ { "id": "Higaki", "label": "Group Higaki", "parent": "Ueda", "type": "group" }, { "id": "Ueda", "label": "Team Ueda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Afiifah", "last_name": "Machfuudzoh", "name": null }, { "creator_type": "author", "first_name": "Weerasak", "last_name": "Pitaksaringkarn", "name": null }, { "creator_type": "author", "first_name": "Ryo", "last_name": "Koshiba", "name": null }, { "creator_type": "author", "first_name": "Takumi", "last_name": "Higaki", "name": null }, { "creator_type": "author", "first_name": "Randeep", "last_name": "Rakwal", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Ohba", "name": null }, { "creator_type": "author", "first_name": "Masashi", "last_name": "Asahina", "name": null }, { "creator_type": "author", "first_name": "Shinobu", "last_name": "Satoh", "name": null }, { "creator_type": "author", "first_name": "Hiroaki", "last_name": "Iwai", "name": null } ], "identifiers": { "doi": { "normalized": "10.1093/pcp/pcae103" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "39275791" } }, "mesh": [ { "descriptor": "Arabidopsis", "descriptor_ui": "D017360", "major_topic": true }, { "descriptor": "Arabidopsis Proteins", "descriptor_ui": "D029681", "major_topic": true }, { "descriptor": "Cell Proliferation", "descriptor_ui": "D049109", "major_topic": true }, { "descriptor": "Gene Expression Regulation, Plant", "descriptor_ui": "D018506", "major_topic": true }, { "descriptor": "Inflorescence", "descriptor_ui": "D056626", "major_topic": true }, { "descriptor": "Matrix Metalloproteinases", "descriptor_ui": "D020782", "major_topic": false }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": false }, { "descriptor": "Plant Stems", "descriptor_ui": "D018547", "major_topic": true }, { "descriptor": "Wound Healing", "descriptor_ui": "D014945", "major_topic": false } ], "publication": { "conference_name": null, "date": "2024 Sep 13", "date_precision": "day", "issue": "", "normalized_date": "2024-09-13", "pages": "pcae103", "proceedings_title": null, "publisher": "", "title": "Plant & cell physiology", "volume": "", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "At2-MMP is required for attenuation of cell proliferation during wound healing in incised Arabidopsis inflorescence stems.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "In the rapidly evolving field of medical image analysis utilizing artificial intelligence (AI), the selection of appropriate computational models is critical for accurate diagnosis and patient care. This literature review provides a comprehensive comparison of vision transformers (ViTs) and convolutional neural networks (CNNs), the two leading techniques in the field of deep learning in medical imaging. We conducted a survey systematically. Particular attention was given to the robustness, computational efficiency, scalability, and accuracy of these models in handling complex medical datasets. The review incorporates findings from 36 studies and indicates a collective trend that transformer-based models, particularly ViTs, exhibit significant potential in diverse medical imaging tasks, showcasing superior performance when contrasted with conventional CNN models. Additionally, it is evident that pre-training is important for transformer applications. We expect this work to help researchers and practitioners select the most appropriate model for specific medical image analysis tasks, accounting for the current state of the art and future trends in the field.", "classifications": [ { "id": "Hamamoto", "label": "Group Hamamoto", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Satoshi", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Sakaguchi", "name": null }, { "creator_type": "author", "first_name": "Nobuji", "last_name": "Kouno", "name": null }, { "creator_type": "author", "first_name": "Ken", "last_name": "Takasawa", "name": null }, { "creator_type": "author", "first_name": "Kenichi", "last_name": "Ishizu", "name": null }, { "creator_type": "author", "first_name": "Yu", "last_name": "Akagi", "name": null }, { "creator_type": "author", "first_name": "Rina", "last_name": "Aoyama", "name": null }, { "creator_type": "author", "first_name": "Naoki", "last_name": "Teraya", "name": null }, { "creator_type": "author", "first_name": "Amina", "last_name": "Bolatkan", "name": null }, { "creator_type": "author", "first_name": "Norio", "last_name": "Shinkai", "name": null }, { "creator_type": "author", "first_name": "Hidenori", "last_name": "Machino", "name": null }, { "creator_type": "author", "first_name": "Kazuma", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Ken", "last_name": "Asada", "name": null }, { "creator_type": "author", "first_name": "Masaaki", "last_name": "Komatsu", "name": null }, { "creator_type": "author", "first_name": "Syuzo", "last_name": "Kaneko", "name": null }, { "creator_type": "author", "first_name": "Masashi", "last_name": "Sugiyama", "name": null }, { "creator_type": "author", "first_name": "Ryuji", "last_name": "Hamamoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/s10916-024-02105-8" }, "pmcid": { "normalized": "PMC11393140" }, "pmid": { "normalized": "39264388" } }, "mesh": [ { "descriptor": "Artificial Intelligence", "descriptor_ui": "D001185", "major_topic": false }, { "descriptor": "Deep Learning", "descriptor_ui": "D000077321", "major_topic": true }, { "descriptor": "Diagnostic Imaging", "descriptor_ui": "D003952", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Image Processing, Computer-Assisted", "descriptor_ui": "D007091", "major_topic": true }, { "descriptor": "Neural Networks, Computer", "descriptor_ui": "D016571", "major_topic": true } ], "publication": { "conference_name": null, "date": "2024 Sep 12", "date_precision": "day", "issue": "1", "normalized_date": "2024-09-12", "pages": "84", "proceedings_title": null, "publisher": "", "title": "Journal of medical systems", "volume": "48", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Comparison of Vision Transformers and Convolutional Neural Networks in Medical Image Analysis: A Systematic Review.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Microbes have evolved intricate communication systems that enable individual cells of a population to send and receive signals in response to changes in their immediate environment. In the fission yeast Schizosaccharomyces pombe, the oxylipin nitrogen signaling factor (NSF) is part of such communication system, which functions to regulate the usage of different nitrogen sources. Yet, the pathways and mechanisms by which NSF acts are poorly understood. Here, we show that NSF physically interacts with the mitochondrial sulfide:quinone oxidoreductase Hmt2 and that it prompts a change from a fermentation- to a respiration-like gene expression program without any change in the carbon source. Our results suggest that NSF activity is not restricted to nitrogen metabolism alone and that it could function as a rheostat to prepare a population of S. pombe cells for an imminent shortage of their preferred nutrients.", "classifications": [ { "id": "Sodeoka", "label": "Group Sodeoka", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Shin", "last_name": "Ohsawa", "name": null }, { "creator_type": "author", "first_name": "Michaela", "last_name": "Schwaiger", "name": null }, { "creator_type": "author", "first_name": "Vytautas", "last_name": "Iesmantavicius", "name": null }, { "creator_type": "author", "first_name": "Rio", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Hiromitsu", "last_name": "Moriyama", "name": null }, { "creator_type": "author", "first_name": "Hiroaki", "last_name": "Matoba", "name": null }, { "creator_type": "author", "first_name": "Go", "last_name": "Hirai", "name": null }, { "creator_type": "author", "first_name": "Mikiko", "last_name": "Sodeoka", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Akihisa", "last_name": "Matsuyama", "name": null }, { "creator_type": "author", "first_name": "Minoru", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Yoko", "last_name": "Yashiroda", "name": null }, { "creator_type": "author", "first_name": "Marc", "last_name": "Buhler", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s44318-024-00224-z" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "39256560" } }, "mesh": [ { "descriptor": "Gene Expression Regulation, Fungal", "descriptor_ui": "D015966", "major_topic": true }, { "descriptor": "Nitrogen", "descriptor_ui": "D009584", "major_topic": true }, { "descriptor": "Schizosaccharomyces", "descriptor_ui": "D012568", "major_topic": true }, { "descriptor": "Schizosaccharomyces pombe Proteins", "descriptor_ui": "D029702", "major_topic": true }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": true } ], "publication": { "conference_name": null, "date": "2024 Sep 10", "date_precision": "day", "issue": "", "normalized_date": "2024-09-10", "pages": "", "proceedings_title": null, "publisher": "", "title": "The EMBO journal", "volume": "", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Nitrogen signaling factor triggers a respiration-like gene expression program in fission yeast.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: Chemical bioproduction has attracted attention as a key technology in a decarbonized society. In computational design for chemical bioproduction, it is necessary to predict changes in metabolic fluxes when up-/down-regulating enzymatic reactions, that is, responses of the system to enzyme perturbations. Structural sensitivity analysis (SSA) was previously developed as a method to predict qualitative responses to enzyme perturbations on the basis of the structural information of the reaction network. However, the network structural information can sometimes be insufficient to predict qualitative responses unambiguously, which is a practical issue in bioproduction applications. To address this, in this study, we propose BayesianSSA, a Bayesian statistical model based on SSA. BayesianSSA extracts environmental information from perturbation datasets collected in environments of interest and integrates it into SSA predictions. RESULTS: We applied BayesianSSA to synthetic and real datasets of the central metabolic pathway of Escherichia coli. Our result demonstrates that BayesianSSA can successfully integrate environmental information extracted from perturbation data into SSA predictions. In addition, the posterior distribution estimated by BayesianSSA can be associated with the known pathway reported to enhance succinate export flux in previous studies. CONCLUSIONS: We believe that BayesianSSA will accelerate the chemical bioproduction process and contribute to advancements in the field.", "classifications": [ { "id": "Mochizuki", "label": "Group Mochizuki", "parent": "Eiraku", "type": "group" }, { "id": "Eiraku", "label": "Team Eiraku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Shion", "last_name": "Hosoda", "name": null }, { "creator_type": "author", "first_name": "Hisashi", "last_name": "Iwata", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Miura", "name": null }, { "creator_type": "author", "first_name": "Maiko", "last_name": "Tanabe", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Okada", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Mochizuki", "name": null }, { "creator_type": "author", "first_name": "Miwa", "last_name": "Sato", "name": null } ], "identifiers": { "doi": { "normalized": "10.1186/s12859-024-05921-4" }, "pmcid": { "normalized": "PMC11389226" }, "pmid": { "normalized": "39256657" } }, "mesh": [ { "descriptor": "Bayes Theorem", "descriptor_ui": "D001499", "major_topic": true }, { "descriptor": "Computational Biology", "descriptor_ui": "D019295", "major_topic": false }, { "descriptor": "Enzymes", "descriptor_ui": "D004798", "major_topic": false }, { "descriptor": "Escherichia coli", "descriptor_ui": "D004926", "major_topic": true }, { "descriptor": "Metabolic Networks and Pathways", "descriptor_ui": "D053858", "major_topic": true }, { "descriptor": "Models, Statistical", "descriptor_ui": "D015233", "major_topic": false } ], "publication": { "conference_name": null, "date": "2024 Sep 10", "date_precision": "day", "issue": "1", "normalized_date": "2024-09-10", "pages": "297", "proceedings_title": null, "publisher": "", "title": "BMC bioinformatics", "volume": "25", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "BayesianSSA: a Bayesian statistical model based on structural sensitivity analysis for predicting responses to enzyme perturbations in metabolic networks.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Surface modification with functional molecules is essential for introducing various surface properties. As gold nanoparticles (AuNPs) have extraordinary chemical, physical, and optical properties, control of their surface, mainly through modification with mixed alkanethiols via Au-S interactions, has attracted much attention. However, surface modification of AuNPs with mixed alkanethiols to provide a strictly regulated composition remains challenging. Further, there are very few methods that can easily establish the nature of ligands and their replacement with similar molecules at nanoparticle surfaces, limiting precise analyses. Herein, we demonstrate an unfair ligand exchange between oligo(ethylene glycol) (OEG)-attached alkanethiols as a source of unfair surface modification utilizing programable thermo-responsive properties of OEG-alkanethiols-modified AuNPs and fair surface modification with mixed OEG-alkanethiols by minimizing this effect. OEG-alkanethiols-modified AuNPs show an assembly/disassembly behavior in response to the solution temperature. Assembly temperature (T (A)) changes in the presence of other OEG-alkanethiols, confirming the ligand exchange between alkanethiols in an aqueous solution. Kinetic analyses indicate that the competitive exchange reaction of these two alkanethiols results in an unfair ligand exchange, which leads to gradual changes in surface composition. As this ligand exchange between alkanethiols takes a longer time compared to that from citric acid, which initially covered the AuNPs, exact surface modification of AuNPs with OEG-alkanethiols is performed by moderate reaction conditions (25 degrees C, several to 24 hours). This insight regarding \"more prolonged reaction is not always better\" could be widely applied for surface modifications with various thiol-ligands.", "classifications": [ { "id": "Nagayama", "label": "Group Nagayama", "parent": "Fujiwara", "type": "group" }, { "id": "Fujiwara", "label": "Team Fujiwara", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Kun", "last_name": "Xiong", "name": null }, { "creator_type": "author", "first_name": "Masaharu", "last_name": "Nagayama", "name": null }, { "creator_type": "author", "first_name": "Kuniharu", "last_name": "Ijiro", "name": null }, { "creator_type": "author", "first_name": "Hideyuki", "last_name": "Mitomo", "name": null } ], "identifiers": { "doi": { "normalized": "10.1039/d4na00270a" }, "pmcid": { "normalized": "PMC11385987" }, "pmid": { "normalized": "39263403" } }, "mesh": [], "publication": { "conference_name": null, "date": "2024 Sep 10", "date_precision": "day", "issue": "18", "normalized_date": "2024-09-10", "pages": "4583-4590", "proceedings_title": null, "publisher": "", "title": "Nanoscale advances", "volume": "6", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Fair surface modification with mixed alkanethiols on gold nanoparticles through minimal unfair ligand exchange.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Insulin-like growth factor (IGF)-I mediates long-term activities that determine cell fate, including cell proliferation and differentiation. This study aimed to characterize the mechanisms by which IGF-I determines cell fate from the aspect of IGF-I signaling dynamics. In L6 myoblasts, myogenic differentiation proceeded under low IGF-I levels, whereas proliferation was enhanced under high levels. Mathematical and experimental analyses revealed that IGF-I signaling oscillated at low IGF-I levels but remained constant at high levels, suggesting that differences in IGF-I signaling dynamics determine cell fate. We previously reported that differential insulin receptor substrate (IRS)-1 levels generate a driving force for cell competition. Computational simulations and immunofluorescence analyses revealed that asynchronous IRS-1 protein oscillations were synchronized during myogenic processes through cell competition. Disturbances of cell competition impaired signaling synchronization and cell fusion, indicating that synchronization of IGF-I signaling oscillation is critical for myoblast cell fusion to form multinucleate myotubes.", "classifications": [ { "id": "Miyamoto", "label": "Group Miyamoto", "parent": "Wakamoto", "type": "group" }, { "id": "Mochizuki", "label": "Group Mochizuki", "parent": "Eiraku", "type": "group" }, { "id": "Eiraku", "label": "Team Eiraku", "type": "team" }, { "id": "Wakamoto", "label": "Team Wakamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Ryosuke", "last_name": "Okino", "name": null }, { "creator_type": "author", "first_name": "Kazuaki", "last_name": "Mukai", "name": null }, { "creator_type": "author", "first_name": "Shunpei", "last_name": "Oguri", "name": null }, { "creator_type": "author", "first_name": "Masato", "last_name": "Masuda", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Yosuke", "last_name": "Yoneyama", "name": null }, { "creator_type": "author", "first_name": "Sumine", "last_name": "Nagaosa", "name": null }, { "creator_type": "author", "first_name": "Takafumi", "last_name": "Miyamoto", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Mochizuki", "name": null }, { "creator_type": "author", "first_name": "Shin-Ichiro", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Fumihiko", "last_name": "Hakuno", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41598-024-71739-y" }, "pmcid": { "normalized": "PMC11377782" }, "pmid": { "normalized": "39237579" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": true }, { "descriptor": "Cell Fusion", "descriptor_ui": "D002459", "major_topic": false }, { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "Cell Proliferation", "descriptor_ui": "D049109", "major_topic": false }, { "descriptor": "Insulin Receptor Substrate Proteins", "descriptor_ui": "D055504", "major_topic": false }, { "descriptor": "Insulin-Like Growth Factor I", "descriptor_ui": "D007334", "major_topic": true }, { "descriptor": "Muscle Development", "descriptor_ui": "D024510", "major_topic": false }, { "descriptor": "Muscle Fibers, Skeletal", "descriptor_ui": "D018485", "major_topic": false }, { "descriptor": "Myoblasts", "descriptor_ui": "D032446", "major_topic": true }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": true } ], "publication": { "conference_name": null, "date": "2024 Sep 5", "date_precision": "day", "issue": "1", "normalized_date": "2024-09-05", "pages": "20699", "proceedings_title": null, "publisher": "", "title": "Scientific reports", "volume": "14", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "IGF-I concentration determines cell fate by converting signaling dynamics as a bifurcation parameter in L6 myoblasts.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The nature of microRNA (miRNA) dysfunction in carcinogenesis remains controversial because of the complex connection between miRNA structural diversity and biological processes. Here, we found that oncofetal IGF2BP3 regulates the selective production of a subset of 3'-isoforms (3'-isomiRs), including miR-21-5p and Let-7 family, which induces significant changes in their cellular seed occupancy and structural components, establishing a cancer-specific gene expression profile. The D-score, reflecting dominant production of a representative miR-21-5p+C (a 3'-isomiR), discriminated between clinical early-stage lung adenocarcinoma (LUAD) cases with low and high recurrence risks, and was associated with molecular features of cell cycle progression, epithelial-mesenchymal transition pressure, and immune evasion. We found that IGF2BP3 controls the production of miR-21-5p+C by directing the nuclear Drosha complex to select the cleavage site. IGF2BP3 was also involved in the production of 3'-isomiRs of miR-425-5p and miR-454-3p. IGF2BP3-regulated these three miRNAs are suggested to be associated with the regulation of p53, TGF-beta, and TNF pathways in LUAD. Knockdown of IGF2BP3 also induced a selective upregulation of Let-7 3'-isomiRs, leading to increased cellular Let-7 seed occupancy and broad repression of its target genes encoding cell cycle regulators. The D-score is an index that reflects this cellular situation. Our results suggest that the aberrant regulation of miRNA structural diversity is a critical component for controlling cellular networks, thus supporting the establishment of a malignant gene expression profile in early stage LUAD.", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yuko", "last_name": "Fujiwara", "name": null }, { "creator_type": "author", "first_name": "Ryou-U.", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Motonobu", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Michinobu", "last_name": "Umakoshi", "name": null }, { "creator_type": "author", "first_name": "Yoko", "last_name": "Shimada", "name": null }, { "creator_type": "author", "first_name": "Kei", "last_name": "Koyama", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null }, { "creator_type": "author", "first_name": "Shun-Ichi", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Souichi", "last_name": "Koyota", "name": null }, { "creator_type": "author", "first_name": "Yoshihiro", "last_name": "Minamiya", "name": null }, { "creator_type": "author", "first_name": "Hidetoshi", "last_name": "Tahara", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Kono", "name": null }, { "creator_type": "author", "first_name": "Kouya", "last_name": "Shiraishi", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Kohno", "name": null }, { "creator_type": "author", "first_name": "Akiteru", "last_name": "Goto", "name": null }, { "creator_type": "author", "first_name": "Naoto", "last_name": "Tsuchiya", "name": null } ], "identifiers": { "doi": { "normalized": "10.1073/pnas.2407016121" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "39196622" } }, "mesh": [ { "descriptor": "Adenocarcinoma of Lung", "descriptor_ui": "D000077192", "major_topic": true }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Epithelial-Mesenchymal Transition", "descriptor_ui": "D058750", "major_topic": false }, { "descriptor": "Gene Expression Regulation, Neoplastic", "descriptor_ui": "D015972", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Lung Neoplasms", "descriptor_ui": "D008175", "major_topic": true }, { "descriptor": "MicroRNAs", "descriptor_ui": "D035683", "major_topic": true }, { "descriptor": "Ribonuclease III", "descriptor_ui": "D043244", "major_topic": false }, { "descriptor": "RNA-Binding Proteins", "descriptor_ui": "D016601", "major_topic": true } ], "publication": { "conference_name": null, "date": "2024 Sep 3", "date_precision": "day", "issue": "36", "normalized_date": "2024-09-03", "pages": "e2407016121", "proceedings_title": null, "publisher": "", "title": "Proceedings of the National Academy of Sciences of the United States of America", "volume": "121", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Oncofetal IGF2BP3-mediated control of microRNA structural diversity in the malignancy of early-stage lung adenocarcinoma.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Quantum sensing has the potential to improve the sensitivity of chemical sensing by exploiting the characteristics of qubits, which are sensitive to the external environment. Modulation of quantum coherence by target analytes can be a useful tool for quantum sensing. Using molecular qubits is expected to provide excellent sensitivity due to the proximity of the sensor to the target analyte. However, many molecular qubits are used at cryogenic temperatures, and how to make molecular qubits respond to specific analytes remains unclear. Here, we propose a material design in which the coherence time changes in response to a variety of analytes at room temperature. We used the photoexcited triplet, which can be initialized at room temperature, as qubits and introduce them to a metal-organic framework that can flexibly change its pore structure in response to guest adsorption. By changing the local molecular density around the triplet qubits by adsorption of a specific analyte, the mobility of the triplet qubit can be changed, and the coherence time can be made responsive.", "classifications": [ { "id": "Hijikata", "label": "Group Hijikata", "parent": "Tsuchiya", "type": "group" }, { "id": "Tsuchiya", "label": "Team Tsuchiya", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Akio", "last_name": "Yamauchi", "name": null }, { "creator_type": "author", "first_name": "Saiya", "last_name": "Fujiwara", "name": null }, { "creator_type": "author", "first_name": "Nobuo", "last_name": "Kimizuka", "name": null }, { "creator_type": "author", "first_name": "Mizue", "last_name": "Asada", "name": null }, { "creator_type": "author", "first_name": "Motoyasu", "last_name": "Fujiwara", "name": null }, { "creator_type": "author", "first_name": "Toshikazu", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Jenny", "last_name": "Pirillo", "name": null }, { "creator_type": "author", "first_name": "Yuh", "last_name": "Hijikata", "name": null }, { "creator_type": "author", "first_name": "Nobuhiro", "last_name": "Yanai", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41467-024-51715-w" }, "pmcid": { "normalized": "PMC11375101" }, "pmid": { "normalized": "39231937" } }, "mesh": [], "publication": { "conference_name": null, "date": "2024 Sep 2", "date_precision": "day", "issue": "1", "normalized_date": "2024-09-02", "pages": "7622", "proceedings_title": null, "publisher": "", "title": "Nature communications", "volume": "15", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Modulation of triplet quantum coherence by guest-induced structural changes in a flexible metal-organic framework.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: The cancer genome contains several driver mutations. However, in some cases, no known drivers have been identified; these remaining areas of unmet needs, leading to limited progress in cancer therapy. Whole-genome sequencing (WGS) can identify non-coding alterations associated with the disease. Consequently, exploration of non-coding regions using WGS and other omics data such as ChIP-sequencing (ChIP-seq) to discern novel alterations and mechanisms related to tumorigenesis have been attractive these days. METHODS: Integrated multi-omics analyses, including WGS, ChIP-seq, DNA methylation, and RNA-sequencing (RNA-seq), were conducted on samples from patients with non-clinically actionable genetic alterations (non-CAGAs) in lung adenocarcinoma (LUAD). Second-level cluster analysis was performed to reinforce the correlations associated with patient survival, as identified by RNA-seq. Subsequent differential gene expression analysis was performed to identify potential druggable targets. RESULTS: Differences in H3K27ac marks in non-CAGAs LUAD were found and confirmed by analyzing RNA-seq data, in which mastermind-like transcriptional coactivator 2 (MAML2) was suppressed. The down-regulated genes whose expression was correlated to MAML2 expression were associated with patient prognosis. WGS analysis revealed somatic mutations associated with the H3K27ac marks in the MAML2 region and high levels of DNA methylation in MAML2 were observed in tumor samples. The second-level cluster analysis enabled patient stratification and subsequent analyses identified potential therapeutic target genes and treatment options. CONCLUSIONS: We overcome the persistent challenges of identifying alterations or driver mutations in coding regions related to tumorigenesis through a novel approach combining multi-omics data with clinical information to reveal the molecular mechanisms underlying non-CAGAs LUAD, stratify patients to improve patient prognosis, and identify potential therapeutic targets. This approach may be applicable to studies of other cancers with unmet needs.", "classifications": [ { "id": "Hamamoto", "label": "Group Hamamoto", "parent": "Okamoto", "type": "group" }, { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Ken", "last_name": "Asada", "name": null }, { "creator_type": "author", "first_name": "Syuzo", "last_name": "Kaneko", "name": null }, { "creator_type": "author", "first_name": "Ken", "last_name": "Takasawa", "name": null }, { "creator_type": "author", "first_name": "Kouya", "last_name": "Shiraishi", "name": null }, { "creator_type": "author", "first_name": "Norio", "last_name": "Shinkai", "name": null }, { "creator_type": "author", "first_name": "Yoko", "last_name": "Shimada", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Hidenori", "last_name": "Machino", "name": null }, { "creator_type": "author", "first_name": "Kazuma", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Amina", "last_name": "Bolatkan", "name": null }, { "creator_type": "author", "first_name": "Masaaki", "last_name": "Komatsu", "name": null }, { "creator_type": "author", "first_name": "Masayoshi", "last_name": "Yamada", "name": null }, { "creator_type": "author", "first_name": "Mototaka", "last_name": "Miyake", "name": null }, { "creator_type": "author", "first_name": "Hirokazu", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Akiko", "last_name": "Tateishi", "name": null }, { "creator_type": "author", "first_name": "Takaaki", "last_name": "Mizuno", "name": null }, { "creator_type": "author", "first_name": "Yu", "last_name": "Okubo", "name": null }, { "creator_type": "author", "first_name": "Masami", "last_name": "Mukai", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Yukihiro", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Hidehito", "last_name": "Horinouchi", "name": null }, { "creator_type": "author", "first_name": "Shun-Ichi", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Yuichiro", "last_name": "Ohe", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Kohno", "name": null }, { "creator_type": "author", "first_name": "Ryuji", "last_name": "Hamamoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1186/s12943-024-02093-w" }, "pmcid": { "normalized": "PMC11367768" }, "pmid": { "normalized": "39218851" } }, "mesh": [ { "descriptor": "Adenocarcinoma of Lung", "descriptor_ui": "D000077192", "major_topic": true }, { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Biomarkers, Tumor", "descriptor_ui": "D014408", "major_topic": false }, { "descriptor": "Cluster Analysis", "descriptor_ui": "D016000", "major_topic": false }, { "descriptor": "DNA Methylation", "descriptor_ui": "D019175", "major_topic": true }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Gene Expression Profiling", "descriptor_ui": "D020869", "major_topic": false }, { "descriptor": "Gene Expression Regulation, Neoplastic", "descriptor_ui": "D015972", "major_topic": true }, { "descriptor": "Genomics", "descriptor_ui": "D023281", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Lung Neoplasms", "descriptor_ui": "D008175", "major_topic": true }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Molecular Targeted Therapy", "descriptor_ui": "D058990", "major_topic": false }, { "descriptor": "Multiomics", "descriptor_ui": "D000095028", "major_topic": false }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": false }, { "descriptor": "Prognosis", "descriptor_ui": "D011379", "major_topic": false }, { "descriptor": "Whole Genome Sequencing", "descriptor_ui": "D000073336", "major_topic": false } ], "publication": { "conference_name": null, "date": "2024 Sep 2", "date_precision": "day", "issue": "1", "normalized_date": "2024-09-02", "pages": "182", "proceedings_title": null, "publisher": "", "title": "Molecular cancer", "volume": "23", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Multi-omics and clustering analyses reveal the mechanisms underlying unmet needs for patients with lung adenocarcinoma and identify potential therapeutic targets.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "In eukaryotic cell nuclei, specific sets of proteins gather in nuclear bodies and facilitate distinct genomic processes. The nucleolus, a nuclear body, functions as a factory for ribosome biogenesis by accumulating constitutive proteins, such as RNA polymerase I and nucleophosmin 1 (NPM1). Although in vitro assays have suggested the importance of liquid-liquid phase separation (LLPS) of constitutive proteins in nucleolar formation, how the nucleolus is structurally maintained with intranuclear architecture remains unknown. This study revealed that the nucleolus is encapsulated by single-stranded (ss) DNA-based molecular complex inside the cell nucleus. Super-resolution lattice-structured illumination microscopy (lattice-SIM) showed high abundance of ssDNA beyond the \"outer shell\" of the nucleolus. Nucleolar disruption and the release of NPM1 were caused by in situ digestion of ssDNA, suggesting that ssDNA has a structural role in nucleolar encapsulation. Furthermore, we identified that ssDNA forms molecular complex with histone H1 for nucleolar encapsulation. Thus, this study illustrates how ssDNA-based molecular complex uphold the structural integrity of nuclear bodies to coordinate genomic processes such as gene transcription and replication.", "classifications": [ { "id": "JPMJCR2023", "label": "JPMJCR2023", "researcher": "Fumiko Toyoshima", "type": "grant" }, { "id": "Maki", "label": "Group Maki", "parent": "Toyoshima", "type": "group" }, { "id": "Toyoshima", "label": "Group Toyoshima", "parent": "Toyoshima", "type": "group" }, { "id": "Toyoshima", "label": "Team Toyoshima", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Koichiro", "last_name": "Maki", "name": null }, { "creator_type": "author", "first_name": "Jumpei", "last_name": "Fukute", "name": null }, { "creator_type": "author", "first_name": "Taiji", "last_name": "Adachi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1242/jcs.262039" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "39206638" } }, "mesh": [ { "descriptor": "Cell Nucleolus", "descriptor_ui": "D002466", "major_topic": true }, { "descriptor": "DNA, Single-Stranded", "descriptor_ui": "D004277", "major_topic": true }, { "descriptor": "HeLa Cells", "descriptor_ui": "D006367", "major_topic": false }, { "descriptor": "Histones", "descriptor_ui": "D006657", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Nuclear Proteins", "descriptor_ui": "D009687", "major_topic": false }, { "descriptor": "Nucleophosmin", "descriptor_ui": "D000090243", "major_topic": true } ], "publication": { "conference_name": null, "date": "2024 Aug 29", "date_precision": "day", "issue": "", "normalized_date": "2024-08-29", "pages": "jcs.262039", "proceedings_title": null, "publisher": "", "title": "Journal of cell science", "volume": "", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Super-resolution imaging reveals nucleolar encapsulation by single-stranded DNA.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "OBJECTIVE: The 2023 International Federation of Gynecology and Obstetrics classification with molecular classification shows superior discriminatory ability compared to staging systems lacking molecular data. However, the accuracy of endometrial biopsy data in molecular classification remains uncertain. This study aimed to assess the concordance of molecular classifications between preoperative biopsy and hysterectomy to predict prognosis before surgical staging. METHODS: Endometrial biopsies and corresponding hysterectomy specimens were collected at the National Cancer Center Hospital between 2012 and 2023. Immunohistochemistry for p53 and mismatch repair (MMR) proteins and next-generation sequencing of all exons of polymerase epsilon (POLE) were performed. Given the limited number of POLE mut cases in prior studies, we prepared a POLE mut-enriched cohort. Cohen's kappa estimates were used to determine concordance for molecular and clinicopathological subgroup assignments. RESULTS: Among 70 patients classified into four molecular subtype groups, 33 exhibited POLE mutations, 15 showed loss of MMR protein expression, 13 had p53-abnormality, and 9 had no specific molecular profile. Concordance between biopsy and hysterectomy specimens was 100% (kappa = 1.000). In contrast, histological types and grades between biopsy and surgical specimens showed moderate and substantial agreement (kappa = 0.420 and kappa = 0.780, respectively). CONCLUSIONS: Molecular subtypes were completely consistent with those derived from surgical specimens, demonstrating high concordance between preoperative and postoperative molecular classifications. This suggests that endometrial biopsies could reliably predict prognosis. Future studies should investigate how biopsy-based molecular profiling influences treatment planning and patient outcomes.", "classifications": [ { "id": "Hamamoto", "label": "Group Hamamoto", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Mayumi Kobayashi", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Erisa", "last_name": "Fujii", "name": null }, { "creator_type": "author", "first_name": "Maiko", "last_name": "Yamaguchi", "name": null }, { "creator_type": "author", "first_name": "Daiki", "last_name": "Higuchi", "name": null }, { "creator_type": "author", "first_name": "Yuka", "last_name": "Asami", "name": null }, { "creator_type": "author", "first_name": "Kengo", "last_name": "Hiranuma", "name": null }, { "creator_type": "author", "first_name": "Masaaki", "last_name": "Komatsu", "name": null }, { "creator_type": "author", "first_name": "Ryuji", "last_name": "Hamamoto", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Matumoto", "name": null }, { "creator_type": "author", "first_name": "Tomoyasu", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Kohno", "name": null }, { "creator_type": "author", "first_name": "Mitsuya", "last_name": "Ishikawa", "name": null }, { "creator_type": "author", "first_name": "Kouya", "last_name": "Shiraishi", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Yoshida", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.ygyno.2024.08.016" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "39191063" } }, "mesh": [ { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Aged, 80 and over", "descriptor_ui": "D000369", "major_topic": false }, { "descriptor": "Biopsy", "descriptor_ui": "D001706", "major_topic": false }, { "descriptor": "DNA Mismatch Repair", "descriptor_ui": "D053843", "major_topic": false }, { "descriptor": "DNA Polymerase II", "descriptor_ui": "D004257", "major_topic": true }, { "descriptor": "Endometrial Neoplasms", "descriptor_ui": "D016889", "major_topic": true }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Hysterectomy", "descriptor_ui": "D007044", "major_topic": true }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": false }, { "descriptor": "Neoplasm Staging", "descriptor_ui": "D009367", "major_topic": false }, { "descriptor": "Poly-ADP-Ribose Binding Proteins", "descriptor_ui": "D000075223", "major_topic": false }, { "descriptor": "Tumor Suppressor Protein p53", "descriptor_ui": "D016159", "major_topic": false } ], "publication": { "conference_name": null, "date": "2024 Aug 26", "date_precision": "day", "issue": "", "normalized_date": "2024-08-26", "pages": "139-145", "proceedings_title": null, "publisher": "", "title": "Gynecologic oncology", "volume": "190", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Excellent concordance of the molecular classification between preoperative biopsy and final hysterectomy in endometrial carcinoma.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Metabolic abnormalities play a pivotal role in various pathological conditions, necessitating the quantification of specific metabolites for diagnosis. While mass spectrometry remains the primary method for metabolite measurement, its limited throughput underscores the need for biosensors capable of rapid detection. Previously, we reported that pillar[6]arene with 12 carboxylate groups (P6AC) forms host-guest complexes with 1-methylnicotinamide (1-MNA), which is produced in vivo by nicotinamide N-methyltransferase (NNMT). P6AC acts as a biosensor by measuring the fluorescence quenching caused by photoinduced electron transfer upon 1-MNA binding. However, the low sensitivity of P6AC makes it impractical for detecting 1-MNA in unpurified biological samples. In this study, we found that P6A with 12 sulfonate groups (P6AS) is a specific and potent supramolecular host for 1-MNA interactions even in biological samples. The 1-MNA binding affinity of P6AS in water was found to be (5.68 +/- 1.02) x 10(6) M(-1), which is approximately 700-fold higher than that of P6AC. Moreover, the 1-MNA detection limit of P6AS was determined to be 2.84 x 10(-7) M, which is substantially lower than that of P6AC. Direct addition of P6AS to culture medium was sufficient to quantify 1-MNA produced by cancer cells. Furthermore, this sensor was able to specifically detect 1-MNA even in unpurified human urine. P6AS therefore enables rapid and high-throughput quantification of 1-MNA, and further improvement of our strategy will contribute to the establishment of high-throughput screening of NNMT inhibitors, diagnosis of liver diseases, and imaging of human cancer cells in vivo.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Masaya", "last_name": "Ueno", "name": null }, { "creator_type": "author", "first_name": "Hiroki", "last_name": "Sugiyama", "name": null }, { "creator_type": "author", "first_name": "Feng", "last_name": "Li", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Nishimura", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Arakawa", "name": null }, { "creator_type": "author", "first_name": "Xi", "last_name": "Chen", "name": null }, { "creator_type": "author", "first_name": "Xiaoxiao", "last_name": "Cheng", "name": null }, { "creator_type": "author", "first_name": "Shinji", "last_name": "Takeuchi", "name": null }, { "creator_type": "author", "first_name": "Yumie", "last_name": "Takeshita", "name": null }, { "creator_type": "author", "first_name": "Toshinari", "last_name": "Takamura", "name": null }, { "creator_type": "author", "first_name": "Sakae", "last_name": "Miyagi", "name": null }, { "creator_type": "author", "first_name": "Tadashi", "last_name": "Toyama", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Masuo", "name": null }, { "creator_type": "author", "first_name": "Yukio", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Hiromasa", "last_name": "Tsujiguchi", "name": null }, { "creator_type": "author", "first_name": "Akinori", "last_name": "Hara", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Tajima", "name": null }, { "creator_type": "author", "first_name": "Moeko", "last_name": "Noguchi-Shinohara", "name": null }, { "creator_type": "author", "first_name": "Kenjiro", "last_name": "Ono", "name": null }, { "creator_type": "author", "first_name": "Kenta", "last_name": "Kurayoshi", "name": null }, { "creator_type": "author", "first_name": "Masahiko", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Yuko", "last_name": "Tadokoro", "name": null }, { "creator_type": "author", "first_name": "Atsuko", "last_name": "Kasahara", "name": null }, { "creator_type": "author", "first_name": "Mahmoud I.", "last_name": "Shoulkamy", "name": null }, { "creator_type": "author", "first_name": "Katsuhiro", "last_name": "Maeda", "name": null }, { "creator_type": "author", "first_name": "Tomoki", "last_name": "Ogoshi", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Hirao", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/acs.analchem.4c02653" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "39183562" } }, "mesh": [ { "descriptor": "Biosensing Techniques", "descriptor_ui": "D015374", "major_topic": true }, { "descriptor": "Calixarenes", "descriptor_ui": "D047250", "major_topic": false }, { "descriptor": "High-Throughput Screening Assays", "descriptor_ui": "D057166", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Niacin", "descriptor_ui": "D009525", "major_topic": false }, { "descriptor": "Niacinamide", "descriptor_ui": "D009536", "major_topic": false }, { "descriptor": "Nicotinamide N-Methyltransferase", "descriptor_ui": "D050903", "major_topic": false } ], "publication": { "conference_name": null, "date": "2024 Aug 25", "date_precision": "day", "issue": "", "normalized_date": "2024-08-25", "pages": "", "proceedings_title": null, "publisher": "", "title": "Analytical chemistry", "volume": "", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "A Supramolecular Biosensor for Rapid and High-Throughput Quantification of a Disease-Associated Niacin Metabolite.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Autosomal dominant optic atrophy (DOA) is a progressive form of blindness caused by degeneration of retinal ganglion cells and their axons, mainly caused by mutations in the OPA1 mitochondrial dynamin like GTPase (OPA1) gene. OPA1 encodes a dynamin-like GTPase present in the mitochondrial inner membrane. When associated with OPA1 mutations, DOA can present not only ocular symptoms but also multi-organ symptoms (DOA plus). DOA plus often results from point mutations in the GTPase domain, which are assumed to have dominant-negative effects. However, the presence of mutations in the GTPase domain does not always result in DOA plus. Therefore, an experimental system to distinguish between DOA and DOA plus is needed. In this study, we found that loss-of-function mutations of the dOPA1 gene in Drosophila can imitate the pathology of optic nerve degeneration observed in DOA. We successfully rescued this degeneration by expressing the human OPA1 (hOPA1) gene, indicating that hOPA1 is functionally interchangeable with dOPA1 in the fly system. However, mutations previously identified did not ameliorate the dOPA1 deficiency phenotype. By expressing both WT and DOA plus mutant hOPA1 forms in the optic nerve of dOPA1 mutants, we observed that DOA plus mutations suppressed the rescue, facilitating the distinction between loss-of-function and dominant-negative mutations in hOPA1. This fly model aids in distinguishing DOA from DOA plus and guides initial hOPA1 mutation treatment strategies.", "classifications": [ { "id": "Suzuki", "label": "Group Suzuki", "parent": "Takekawa", "type": "group" }, { "id": "Takekawa", "label": "Team Takekawa", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yohei", "last_name": "Nitta", "name": null }, { "creator_type": "author", "first_name": "Jiro", "last_name": "Osaka", "name": null }, { "creator_type": "author", "first_name": "Ryuto", "last_name": "Maki", "name": null }, { "creator_type": "author", "first_name": "Satoko", "last_name": "Hakeda-Suzuki", "name": null }, { "creator_type": "author", "first_name": "Emiko", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Ueki", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Sugie", "name": null } ], "identifiers": { "doi": { "normalized": "10.7554/elife.87880" }, "pmcid": { "normalized": "PMC11343565" }, "pmid": { "normalized": "39177028" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Disease Models, Animal", "descriptor_ui": "D004195", "major_topic": true }, { "descriptor": "Drosophila", "descriptor_ui": "D004330", "major_topic": false }, { "descriptor": "Drosophila melanogaster", "descriptor_ui": "D004331", "major_topic": false }, { "descriptor": "Drosophila Proteins", "descriptor_ui": "D029721", "major_topic": true }, { "descriptor": "GTP Phosphohydrolases", "descriptor_ui": "D020558", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Membrane Proteins", "descriptor_ui": "D008565", "major_topic": false }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": false }, { "descriptor": "Optic Atrophy, Autosomal Dominant", "descriptor_ui": "D029241", "major_topic": true } ], "publication": { "conference_name": null, "date": "2024 Aug 23", "date_precision": "day", "issue": "", "normalized_date": "2024-08-23", "pages": "", "proceedings_title": null, "publisher": "", "title": "eLife", "volume": "12", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Drosophila model to clarify the pathological significance of OPA1 in autosomal dominant optic atrophy.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Given the worldwide risk for the outbreak of emerging/re-emerging respiratory viruses, establishment of new antiviral strategies is greatly demanded. In this study, we present a scheme to identify gapmer antisense oligonucleotides (ASOs) targeting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA that efficiently inhibit viral replication. We synthesized approximately 300 gapmer ASOs designed to target various SARS-CoV-2 RNA regions and evaluated their activity in cell-based assays. Through a multistep screening in cell culture systems, we identified that ASO#41, targeting the coding region for viral main protease, reduced SARS-CoV-2 RNA levels in infected cells and inhibited virus-induced cytopathic effects. Antiviral effect of ASO#41 was also observed in iPS cell-derived human lung organoids. ASO#41 depleted intracellular viral RNAs during genome replication in an endogenous RNaseH-dependent manner. ASO#41 showed a wide range of antiviral activity against SARS-CoV-2 variants of concern including Alpha, Delta, and Omicron. Intranasal administration to mice exhibited intracellular accumulation of ASO#41 in the lung and significantly reduced the viral infectious titer, with milder body weight loss due to SARS-CoV-2 infection. Further chemical modification with phosphoryl guanidine-containing backbone linkages provided an elevation of anti-SARS-CoV-2 activity, with 23.4 nM of 50% antiviral inhibitory concentration, one of the strongest anti-SARS-CoV-2 ASOs reported so far. Our study presents an approach to identify active ASOs against SARS-CoV-2, which is potentially useful for establishing an antiviral strategy by targeting genome RNA of respiratory viruses.", "classifications": [ { "id": "Yamamoto", "label": "Group Yamamoto", "parent": "Toyoshima", "type": "group" }, { "id": "Toyoshima", "label": "Team Toyoshima", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Masako", "last_name": "Yamasaki", "name": null }, { "creator_type": "author", "first_name": "Wakana", "last_name": "Saso", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Masayoshi", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Hiroko", "last_name": "Takagi", "name": null }, { "creator_type": "author", "first_name": "Tetsuya", "last_name": "Hasegawa", "name": null }, { "creator_type": "author", "first_name": "Yuji", "last_name": "Kozakura", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Yokoi", "name": null }, { "creator_type": "author", "first_name": "Hirofumi", "last_name": "Ohashi", "name": null }, { "creator_type": "author", "first_name": "Kana", "last_name": "Tsuchimoto", "name": null }, { "creator_type": "author", "first_name": "Rina", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Shuetsu", "last_name": "Fukushi", "name": null }, { "creator_type": "author", "first_name": "Akihiko", "last_name": "Uda", "name": null }, { "creator_type": "author", "first_name": "Masamichi", "last_name": "Muramatsu", "name": null }, { "creator_type": "author", "first_name": "Kazuo", "last_name": "Takayama", "name": null }, { "creator_type": "author", "first_name": "Ken", "last_name": "Maeda", "name": null }, { "creator_type": "author", "first_name": "Yoshimasa", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Tsuyoshi", "last_name": "Nagase", "name": null }, { "creator_type": "author", "first_name": "Koichi", "last_name": "Watashi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.antiviral.2024.105992" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "39181215" } }, "mesh": [ { "descriptor": "Administration, Intranasal", "descriptor_ui": "D000281", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "COVID-19", "descriptor_ui": "D000086382", "major_topic": false }, { "descriptor": "Disease Models, Animal", "descriptor_ui": "D004195", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Induced Pluripotent Stem Cells", "descriptor_ui": "D057026", "major_topic": false }, { "descriptor": "Lung", "descriptor_ui": "D008168", "major_topic": false }, { "descriptor": "Mice, Inbred BALB C", "descriptor_ui": "D008807", "major_topic": false }, { "descriptor": "Oligonucleotides, Antisense", "descriptor_ui": "D016376", "major_topic": true }, { "descriptor": "Organoids", "descriptor_ui": "D009940", "major_topic": false }, { "descriptor": "Peptide Hydrolases", "descriptor_ui": "D010447", "major_topic": true }, { "descriptor": "Ribonuclease H", "descriptor_ui": "D016914", "major_topic": false }, { "descriptor": "RNA, Viral", "descriptor_ui": "D012367", "major_topic": true }, { "descriptor": "SARS-CoV-2", "descriptor_ui": "D000086402", "major_topic": true } ], "publication": { "conference_name": null, "date": "2024 Aug 22", "date_precision": "day", "issue": "", "normalized_date": "2024-08-22", "pages": "105992", "proceedings_title": null, "publisher": "", "title": "Antiviral research", "volume": "", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Anti-SARS-CoV-2 gapmer antisense oligonucleotides targeting the main protease region of viral RNA.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The precise onset of flowering is crucial to ensure successful plant reproduction. The gene FLOWERING LOCUS T (FT) encodes florigen, a mobile signal produced in leaves that initiates flowering at the shoot apical meristem. In response to seasonal changes, FT is induced in phloem companion cells located in distal leaf regions. Thus far, a detailed molecular characterization of the FT-expressing cells has been lacking. Here, we used bulk nuclei RNA-seq and single nuclei RNA (snRNA)-seq to investigate gene expression in FT-expressing cells and other phloem companion cells. Our bulk nuclei RNA-seq demonstrated that FT-expressing cells in cotyledons and in true leaves differed transcriptionally. Within the true leaves, our snRNA-seq analysis revealed that companion cells with high FT expression form a unique cluster in which many genes involved in ATP biosynthesis are highly upregulated. The cluster also expresses other genes encoding small proteins, including the flowering and stem growth inducer FPF1-LIKE PROTEIN 1 (FLP1) and the anti-florigen BROTHER OF FT AND TFL1 (BFT). In addition, we found that the promoters of FT and the genes co-expressed with FT in the cluster were enriched for the consensus binding motifs of NITRATE-INDUCIBLE GARP-TYPE TRANSCRIPTIONAL REPRESSOR 1 (NIGT1). Overexpression of the paralogous NIGT1.2 and NIGT1.4 repressed FT expression and significantly delayed flowering under nitrogen-rich conditions, consistent with NIGT1s acting as nitrogen-dependent FT repressors. Taken together, our results demonstrate that major FT-expressing cells show a distinct expression profile that suggests that these cells may produce multiple systemic signals to regulate plant growth and development.", "classifications": [ { "id": "Sato", "label": "Group Sato", "parent": "Tsuchiya", "type": "group" }, { "id": "Tsuchiya", "label": "Team Tsuchiya", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Takagi", "name": null }, { "creator_type": "author", "first_name": "Shogo", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Jae Sung", "last_name": "Shim", "name": null }, { "creator_type": "author", "first_name": "Akane", "last_name": "Kubota", "name": null }, { "creator_type": "author", "first_name": "Andrew K.", "last_name": "Hempton", "name": null }, { "creator_type": "author", "first_name": "Nayoung", "last_name": "Lee", "name": null }, { "creator_type": "author", "first_name": "Takamasa", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Chansie", "last_name": "Yang", "name": null }, { "creator_type": "author", "first_name": "Christine T.", "last_name": "Nolan", "name": null }, { "creator_type": "author", "first_name": "Kerry L.", "last_name": "Bubb", "name": null }, { "creator_type": "author", "first_name": "Cristina M.", "last_name": "Alexandre", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Kurihara", "name": null }, { "creator_type": "author", "first_name": "Yoshikatsu", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Yasuomi", "last_name": "Tada", "name": null }, { "creator_type": "author", "first_name": "Takatoshi", "last_name": "Kiba", "name": null }, { "creator_type": "author", "first_name": "Jose L.", "last_name": "Pruneda-Paz", "name": null }, { "creator_type": "author", "first_name": "Christine", "last_name": "Queitsch", "name": null }, { "creator_type": "author", "first_name": "Josh T.", "last_name": "Cuperus", "name": null }, { "creator_type": "author", "first_name": "Takato", "last_name": "Imaizumi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1101/2024.08.17.608367" }, "pmcid": { "normalized": null }, "pmid": { "normalized": null } }, "mesh": [], "publication": { "conference_name": null, "date": "2024 Aug 19", "date_precision": "day", "issue": null, "normalized_date": "2024-08-19", "pages": null, "proceedings_title": null, "publisher": null, "title": null, "volume": null, "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "A florigen-expressing subpopulation of companion cells expresses other small proteins and reveals a nitrogen-sensitive FT repressor.", "url": "", "zotero": { "item_type": "preprint" } }, { "abstract": "Although many host factors important for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection have been reported, the mechanisms by which the virus interacts with host cells remain elusive. Here, we identified tripartite motif containing (TRIM) 28, TRIM33, euchromatic histone lysine methyltransferase (EHMT) 1, and EHMT2 as proviral factors involved in SARS-CoV-2 infection by CRISPR-Cas9 screening. Our result suggested that TRIM28 may play a role in viral particle formation and that TRIM33, EHMT1, and EHMT2 may be involved in viral transcription and replication. UNC0642, a compound that specifically inhibits the methyltransferase activity of EHMT1/2, strikingly suppressed SARS-CoV-2 growth in cultured cells and reduced disease severity in a hamster infection model. This study suggests that EHMT1/2 may be a therapeutic target for SARS-CoV-2 infection.", "classifications": [ { "id": "Yusa", "label": "Group Yusa", "parent": "Eiraku", "type": "group" }, { "id": "Eiraku", "label": "Team Eiraku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Madoka", "last_name": "Sakai", "name": null }, { "creator_type": "author", "first_name": "Yoshie", "last_name": "Masuda", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Tarumoto", "name": null }, { "creator_type": "author", "first_name": "Naoyuki", "last_name": "Aihara", "name": null }, { "creator_type": "author", "first_name": "Yugo", "last_name": "Tsunoda", "name": null }, { "creator_type": "author", "first_name": "Michiko", "last_name": "Iwata", "name": null }, { "creator_type": "author", "first_name": "Yumiko", "last_name": "Kamiya", "name": null }, { "creator_type": "author", "first_name": "Ryo", "last_name": "Komorizono", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Noda", "name": null }, { "creator_type": "author", "first_name": "Kosuke", "last_name": "Yusa", "name": null }, { "creator_type": "author", "first_name": "Keizo", "last_name": "Tomonaga", "name": null }, { "creator_type": "author", "first_name": "Akiko", "last_name": "Makino", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.isci.2024.110475" }, "pmcid": { "normalized": "PMC11295705" }, "pmid": { "normalized": "39100693" } }, "mesh": [], "publication": { "conference_name": null, "date": "2024 Aug 16", "date_precision": "day", "issue": "8", "normalized_date": "2024-08-16", "pages": "110475", "proceedings_title": null, "publisher": "", "title": "iScience", "volume": "27", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Genome-scale CRISPR-Cas9 screen identifies host factors as potential therapeutic targets for SARS-CoV-2 infection.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Recent studies reveal that biosynthesis of iron-sulfur clusters (Fe-Ss) is essential for cell proliferation, including that of cancer cells. Nonetheless, it remains unclear how Fe-S biosynthesis functions in cell proliferation/survival. Here, we report that proper Fe-S biosynthesis is essential to prevent cellular senescence, apoptosis or ferroptosis, depending on cell context. To assess these outcomes in cancer, we developed an ovarian cancer line with conditional KO of FDX2, a component of the core Fe-S assembly complex. FDX2 loss induced global down-regulation of Fe-S-containing proteins and Fe(2+) overload, resulting in DNA damage and p53 pathway activation, and driving the senescence program. p53-deficiency augmented DNA damage responses upon FDX2 loss, resulting in apoptosis rather than senescence. FDX2 loss also sensitized cells to ferroptosis, as evidenced by compromised redox homeostasis of membrane phospholipids (PLs). Our results suggest that p53 status and PL homeostatic activity are critical determinants of diverse biological outcomes of Fe-S deficiency in cancer cells.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Shuko", "last_name": "Miyahara", "name": null }, { "creator_type": "author", "first_name": "Mai", "last_name": "Ohuchi", "name": null }, { "creator_type": "author", "first_name": "Miyuki", "last_name": "Nomura", "name": null }, { "creator_type": "author", "first_name": "Eifumi", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Rintaro", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Kayoko", "last_name": "Hayashi", "name": null }, { "creator_type": "author", "first_name": "Taku", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Masatoshi", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Yoji", "last_name": "Yamashita", "name": null }, { "creator_type": "author", "first_name": "Muneaki", "last_name": "Shimada", "name": null }, { "creator_type": "author", "first_name": "Nobuo", "last_name": "Yaegashi", "name": null }, { "creator_type": "author", "first_name": "Hidekazu", "last_name": "Yamada", "name": null }, { "creator_type": "author", "first_name": "Nobuhiro", "last_name": "Tanuma", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.jbc.2024.107678" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "39151727" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Apoptosis", "descriptor_ui": "D017209", "major_topic": true }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Cellular Senescence", "descriptor_ui": "D016922", "major_topic": true }, { "descriptor": "DNA Damage", "descriptor_ui": "D004249", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Ferroptosis", "descriptor_ui": "D000079403", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Iron", "descriptor_ui": "D007501", "major_topic": false }, { "descriptor": "Iron-Sulfur Proteins", "descriptor_ui": "D007506", "major_topic": true }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Ovarian Neoplasms", "descriptor_ui": "D010051", "major_topic": true }, { "descriptor": "Tumor Suppressor Protein p53", "descriptor_ui": "D016159", "major_topic": true } ], "publication": { "conference_name": null, "date": "2024 Aug 14", "date_precision": "day", "issue": "", "normalized_date": "2024-08-14", "pages": "107678", "proceedings_title": null, "publisher": "", "title": "The Journal of biological chemistry", "volume": "", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "FDX2, an iron-sulfur cluster assembly factor, is essential to prevent cellular senescence, apoptosis or ferroptosis of ovarian cancer cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: Psychological resilience is defined as the process and outcome of individuals' successful adaptation to challenging life experiences. The Habenula (Hb) is known to be involved in the stress response; however, the relationship between Hb volume and resilience in humans remains unclear. This study investigated the correlation among resilience, Hb volume, and depressive tendencies in adults. METHODS: Hb volumes were assessed using deep learning techniques applied to 110 healthy participants. Resilience and depression were evaluated using the Connor-Davidson Resilience Scale and Beck Depression Inventory-II, respectively. We examined the relationship between Hb volume and resilience and assessed the mediating effects of resilience on the relationship between Hb volume and depressive tendencies. RESULTS: Correlation analysis revealed a positive correlation between resilience and Hb volume (partial r = 0.176, p = 0.001), which was more pronounced in women (partial r = 0.353, p = 0.003). Hb volumes on the left and right sides exhibited significant lateralization (LI = 0.031, 95 % CI = [0.016, 0.046]). Despite Hb asymmetry, lateralization was not significantly associated with resilience. The mediation analysis shows significant indirect effect of resilience on the relationship between Hb volume and depressive tendencies (beta = -0.093, 95%CI = [-0.189, -0.019]). CONCLUSION: This study found that populations with lower resilience have smaller Hb volume. Previous research has shown that Hb volume decreased with the increasing severity of depression symptoms in patients. Our findings support this view and extend it to a population that has not been clinically diagnosed with depression. Additionally, we found that psychological resilience can be predicted by Hb volume and may serve as a mediating factor indirectly affecting depressive tendencies, even in healthy individuals. LIMITATIONS: Due to its cross-sectional design, this study was unable to analyze dynamic changes in Hb volume during the process of resilience adaptation.", "classifications": [ { "id": "Fujiwara", "label": "Group Fujiwara", "parent": "Fujiwara", "type": "group" }, { "id": "Fujiwara", "label": "Team Fujiwara", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Qi", "last_name": "Dai", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Kyuragi", "name": null }, { "creator_type": "author", "first_name": "Halwa", "last_name": "Zakia", "name": null }, { "creator_type": "author", "first_name": "Naoya", "last_name": "Oishi", "name": null }, { "creator_type": "author", "first_name": "Lichang", "last_name": "Yao", "name": null }, { "creator_type": "author", "first_name": "Zhilin", "last_name": "Zhang", "name": null }, { "creator_type": "author", "first_name": "Luyao", "last_name": "Wang", "name": null }, { "creator_type": "author", "first_name": "Jiajia", "last_name": "Yang", "name": null }, { "creator_type": "author", "first_name": "Toshiya", "last_name": "Murai", "name": null }, { "creator_type": "author", "first_name": "Hironobu", "last_name": "Fujiwara", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.jad.2024.08.012" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "39151760" } }, "mesh": [ { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Depression", "descriptor_ui": "D003863", "major_topic": true }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Habenula", "descriptor_ui": "D019262", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Magnetic Resonance Imaging", "descriptor_ui": "D008279", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Psychiatric Status Rating Scales", "descriptor_ui": "D011569", "major_topic": false }, { "descriptor": "Resilience, Psychological", "descriptor_ui": "D055500", "major_topic": true }, { "descriptor": "Young Adult", "descriptor_ui": "D055815", "major_topic": false } ], "publication": { "conference_name": null, "date": "2024 Aug 14", "date_precision": "day", "issue": "", "normalized_date": "2024-08-14", "pages": "S0165-0327(24)01226-6", "proceedings_title": null, "publisher": "", "title": "Journal of affective disorders", "volume": "", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Psychological resilience is positively correlated with Habenula volume.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "While N-heterocyclic carbenes (NHCs) have recently been shown to be effective ligands for gold nanoclusters, very few examples of heterometallic clusters incorporating nongroup 11 metals are known. We present herein an Au-Pt NHC cluster featuring a crown-shaped [Au(8)Pt(NHC)(8)](2+) core, produced in high yield without the need for chromatographic purification. The method was largely independent of the substitution pattern of the NHC backbone; however, bulky wingtip groups were needed for clean conversion to the Au(8)Pt cluster. Clusters were characterized using single crystal X-ray diffraction, multinuclear nuclear magnetic resonance, electrospray ionization mass spectroscopy, and ultraviolet-visible spectroscopy, and electrochemical features of the cluster are also presented. A detailed analysis of the in-progress reaction mixture by ESI-MS supports the direct involvement of Au-H species as intermediates in cluster formation. These studies further demonstrate that NHC wingtip sterics play a key part in determining the nature of the initial cluster species, providing critical information for the generation of new NHC-stabilized nanoclusters.", "classifications": [ { "id": "Nanbo", "label": "Group Nanbo", "parent": "Tsuchiya", "type": "group" }, { "id": "Tsuchiya", "label": "Team Tsuchiya", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Joseph F.", "last_name": "DeJesus", "name": null }, { "creator_type": "author", "first_name": "Samuel I.", "last_name": "Jacob", "name": null }, { "creator_type": "author", "first_name": "Quan Manh", "last_name": "Phung", "name": null }, { "creator_type": "author", "first_name": "Koichi", "last_name": "Mimura", "name": null }, { "creator_type": "author", "first_name": "Yoshitaka", "last_name": "Aramaki", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Ooi", "name": null }, { "creator_type": "author", "first_name": "Masakazu", "last_name": "Nambo", "name": null }, { "creator_type": "author", "first_name": "Cathleen M.", "last_name": "Crudden", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/jacs.4c04873" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "39141005" } }, "mesh": [], "publication": { "conference_name": null, "date": "2024 Aug 14", "date_precision": "day", "issue": "", "normalized_date": "2024-08-14", "pages": "", "proceedings_title": null, "publisher": "", "title": "Journal of the American Chemical Society", "volume": "", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "If the Crown Fits: Sterically Demanding N-Heterocyclic Carbene Promotes the Formation of Au(8)Pt Nanoclusters.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: Primary analysis of the phase III AGEHA study suggested a favorable benefit-risk profile for emicizumab prophylaxis in patients with acquired hemophilia A (PwAHA); however, only patients undergoing immunosuppressive therapy (IST) (Cohort 1) were included. OBJECTIVES: To present final analysis results of AGEHA, including data on IST-ineligible patients (Cohort 2) and on long-term prophylaxis with emicizumab. METHODS: For patients in both Cohorts 1 and 2, emicizumab was administered subcutaneously at 6 mg/kg on Day 1, 3 mg/kg on Day 2, and 1.5 mg/kg once weekly from Day 8 onward. RESULTS: Twelve patients (Cohort 1) and 2 patients (Cohort 2) were enrolled. Duration of emicizumab treatment was 8-639 days (median: 44.5 days) in Cohort 1 and 64 and 450 days in Cohort 2. In both cohorts, no major bleeds were observed after initial emicizumab administration. Six patients started their first rehabilitation sessions during emicizumab treatment and no rehabilitation-related bleeds occurred. Twenty-three surgeries were performed under emicizumab prophylaxis and there were no bleeds related to surgeries. Although asymptomatic deep vein thrombosis was reported in 1 patient in the primary analysis, no other thrombotic events occurred thereafter. Two patients developed anti-emicizumab antibodies, 1 of whom showed accelerated emicizumab clearance. Tailored IST approaches (delayed initiation, no use, or reduced dose) were successfully executed in 3 patients undergoing emicizumab prophylaxis. CONCLUSIONS: These results suggest that emicizumab prophylaxis has a favorable benefit-risk profile in PwAHA regardless of eligibility for IST.", "classifications": [ { "id": "Nishikii", "label": "Group Nishikii", "parent": "Shintaku", "type": "group" }, { "id": "Shintaku", "label": "Team Shintaku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Midori", "last_name": "Shima", "name": null }, { "creator_type": "author", "first_name": "Nobuaki", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Hidekazu", "last_name": "Nishikii", "name": null }, { "creator_type": "author", "first_name": "Kagehiro", "last_name": "Amano", "name": null }, { "creator_type": "author", "first_name": "Yoshiyuki", "last_name": "Ogawa", "name": null }, { "creator_type": "author", "first_name": "Ryota", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Ryoto", "last_name": "Ozaki", "name": null }, { "creator_type": "author", "first_name": "Koichiro", "last_name": "Yoneyama", "name": null }, { "creator_type": "author", "first_name": "Narumi", "last_name": "Mizuno", "name": null }, { "creator_type": "author", "first_name": "Emiko", "last_name": "Sakaida", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Okamura", "name": null }, { "creator_type": "author", "first_name": "Toshihiro", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Norimichi", "last_name": "Hattori", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Higasa", "name": null }, { "creator_type": "author", "first_name": "Yoshinobu", "last_name": "Seki", "name": null }, { "creator_type": "author", "first_name": "Keiji", "last_name": "Nogami", "name": null } ], "identifiers": { "doi": { "normalized": "10.1055/a-2384-3585" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "39134043" } }, "mesh": [ { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Antibodies, Bispecific", "descriptor_ui": "D018033", "major_topic": true }, { "descriptor": "Antibodies, Monoclonal, Humanized", "descriptor_ui": "D061067", "major_topic": true }, { "descriptor": "Drug Administration Schedule", "descriptor_ui": "D004334", "major_topic": false }, { "descriptor": "Factor VIII", "descriptor_ui": "D005169", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Hemophilia A", "descriptor_ui": "D006467", "major_topic": true }, { "descriptor": "Hemorrhage", "descriptor_ui": "D006470", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Immunosuppressive Agents", "descriptor_ui": "D007166", "major_topic": true }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Time Factors", "descriptor_ui": "D013997", "major_topic": false }, { "descriptor": "Treatment Outcome", "descriptor_ui": "D016896", "major_topic": false }, { "descriptor": "Young Adult", "descriptor_ui": "D055815", "major_topic": false } ], "publication": { "conference_name": null, "date": "2024 Aug 12", "date_precision": "day", "issue": "", "normalized_date": "2024-08-12", "pages": "", "proceedings_title": null, "publisher": "", "title": "Thrombosis and haemostasis", "volume": "", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Final Analysis Results from the AGEHA Study: Emicizumab Prophylaxis for Acquired Hemophilia A with or without Immunosuppressive Therapy.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "EUS-TA in unresectable pancreatic cancer requires not only a tissue diagnosis but also tissue collection in anticipation of comprehensive genomic profiling. However, the optimal puncture target remains controversial. Therefore, the Primary and Metastatic Lesions in Pancreatic Cancer (PRIMATE) study was designed to clarify the optimal target by comparing the success rates for meeting OncoGuide NCC Oncopanel (NOP) analysis criteria on pre-check primary and metastatic lesion specimens obtained during the same EUS-TA session in patients with invasive pancreatic ductal adenocarcinoma. In this ongoing prospective study, two specimens, each from primary and metastatic lesions, are obtained by EUS-TA (typically using a 19G fine-needle biopsy needle) in patients with invasive pancreatic ductal adenocarcinoma. The primary endpoint is the proportion of EUS-TA specimens that meet NOP analysis criteria during pre-check (i.e., tumor cellularity of >/=20% and a tissue area of >/=4 mm(2)), which are then compared between primary and metastatic lesions. This study has been approved by the National Cancer Center Institutional Review Board (Research No. 2022-168). The results of this study will be reported at an international conference and published in an international peer-reviewed journal. The trial registration number is UMIN 000048966.", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Kotaro", "last_name": "Takeshita", "name": null }, { "creator_type": "author", "first_name": "Susumu", "last_name": "Hijioka", "name": null }, { "creator_type": "author", "first_name": "Yoshikuni", "last_name": "Nagashio", "name": null }, { "creator_type": "author", "first_name": "Hidenobu", "last_name": "Hara", "name": null }, { "creator_type": "author", "first_name": "Daiki", "last_name": "Agarie", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Kawasaki", "name": null }, { "creator_type": "author", "first_name": "Tetsuro", "last_name": "Takasaki", "name": null }, { "creator_type": "author", "first_name": "Shin", "last_name": "Yagi", "name": null }, { "creator_type": "author", "first_name": "Yuya", "last_name": "Hagiwara", "name": null }, { "creator_type": "author", "first_name": "Kohei", "last_name": "Okamoto", "name": null }, { "creator_type": "author", "first_name": "Daiki", "last_name": "Yamashige", "name": null }, { "creator_type": "author", "first_name": "Soma", "last_name": "Fukuda", "name": null }, { "creator_type": "author", "first_name": "Masaru", "last_name": "Kuwada", "name": null }, { "creator_type": "author", "first_name": "Yasuhiro", "last_name": "Komori", "name": null }, { "creator_type": "author", "first_name": "Mao", "last_name": "Okada", "name": null }, { "creator_type": "author", "first_name": "Yuta", "last_name": "Maruki", "name": null }, { "creator_type": "author", "first_name": "Chigusa", "last_name": "Morizane", "name": null }, { "creator_type": "author", "first_name": "Hideki", "last_name": "Ueno", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null }, { "creator_type": "author", "first_name": "Takuji", "last_name": "Okusaka", "name": null } ], "identifiers": { "doi": { "normalized": "10.3390/diseases12080182" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "39195181" } }, "mesh": [], "publication": { "conference_name": null, "date": "2024 Aug 12", "date_precision": "day", "issue": "8", "normalized_date": "2024-08-12", "pages": "182", "proceedings_title": null, "publisher": "", "title": "Diseases (Basel, Switzerland)", "volume": "12", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Study Protocol for a Prospective Self-Controlled Trial on Success in Meeting Comprehensive Genomic Profiling Analysis Criteria for Specimens Obtained by Endoscopic Ultrasound-Guided Tissue Acquisition Using a 19G Needle from Primary and Metastatic Lesions in Pancreatic Cancer with Metastatic Lesions: The PRIMATE Study.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: Thyroid hormones (TH) regulate the basal metabolic rate through their receptors THRalpha and THRbeta. TH activates lipid metabolism via THRbeta, however, an excess amount of TH can lead to tachycardia, bone loss, and muscle wasting through THRalpha. In recent years, TH analogs that selectively bind to THRbeta have gained attention as new agents for treating dyslipidemia and obesity, which continue to pose major challenges to public health worldwide. METHODS: We developed a TH analog, ZTA-261, by modifying the existing THRbeta-selective agonists GC-1 and GC-24. To determine the THRbeta-selectivity of ZTA-261, an in vitro radiolabeled TH displacement assay was conducted. ZTA-261 was intraperitoneally injected into a mouse model of high-fat diet-induced obesity, and its effectiveness in reducing body weight and visceral fat, and improving lipid metabolism was assessed. In addition, its toxicity in the liver, heart, and bone was evaluated. RESULTS: ZTA-261 is more selective towards THRbeta than GC-1. Although ZTA-261 is less effective in reducing body weight and visceral fat than GC-1, it is as effective as GC-1 in reducing the levels of serum and liver lipids. These effects are mediated by the same pathway as that of T(3), a natural TH, as evidenced by similar changes in the expression of TH-induced and lipid metabolism-related genes. The bone, cardiac, and hepatotoxicity of ZTA-261 are significantly lower than those of GC-1. CONCLUSIONS: ZTA-261, a highly selective and less toxic THRbeta agonist, has the potential to be used as a drug for treating diseases related to lipid metabolism.", "classifications": [ { "id": "Nanbo", "label": "Group Nanbo", "parent": "Tsuchiya", "type": "group" }, { "id": "Tsuchiya", "label": "Team Tsuchiya", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Masakazu", "last_name": "Nambo", "name": null }, { "creator_type": "author", "first_name": "Taeko", "last_name": "Nishiwaki-Ohkawa", "name": null }, { "creator_type": "author", "first_name": "Akihiro", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Zachary T.", "last_name": "Ariki", "name": null }, { "creator_type": "author", "first_name": "Yuka", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Yuuki", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Muhammad", "last_name": "Yar", "name": null }, { "creator_type": "author", "first_name": "Jacky C.-H.", "last_name": "Yim", "name": null }, { "creator_type": "author", "first_name": "Emily", "last_name": "Kim", "name": null }, { "creator_type": "author", "first_name": "Elizabeth", "last_name": "Sharkey", "name": null }, { "creator_type": "author", "first_name": "Keiko", "last_name": "Kano", "name": null }, { "creator_type": "author", "first_name": "Emi", "last_name": "Mishiro-Sato", "name": null }, { "creator_type": "author", "first_name": "Kosuke", "last_name": "Okimura", "name": null }, { "creator_type": "author", "first_name": "Michiyo", "last_name": "Maruyama", "name": null }, { "creator_type": "author", "first_name": "Wataru", "last_name": "Ota", "name": null }, { "creator_type": "author", "first_name": "Yuko", "last_name": "Furukawa", "name": null }, { "creator_type": "author", "first_name": "Tomoya", "last_name": "Nakayama", "name": null }, { "creator_type": "author", "first_name": "Misato", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Fumihiko", "last_name": "Horio", "name": null }, { "creator_type": "author", "first_name": "Ayato", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Cathleen M.", "last_name": "Crudden", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Yoshimura", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s43856-024-00574-z" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "39107484" } }, "mesh": [], "publication": { "conference_name": null, "date": "2024 Aug 6", "date_precision": "day", "issue": "1", "normalized_date": "2024-08-06", "pages": "152", "proceedings_title": null, "publisher": "", "title": "Communications medicine", "volume": "4", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Synthesis and preclinical testing of a selective beta-subtype agonist of thyroid hormone receptor ZTA-261.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Methods to form carbon-carbon bonds efficiently and with control of stereochemistry are critical for the construction of complex molecules. Cross-coupling reactions are among the most efficient and widely used reactions to construct molecules, with reactions enabling the retention or installation of chirality as recent additions to this powerful toolbox. Sulfones are robust, accessible organic electrophiles that have many attractive features as cross-coupling partners; however, since the first example of their use in 1979, there have been no examples of their use in enantioselective, enantiospecific or entantioconvergent cross-couplings. The high acidity of sulfones makes it unclear whether this transformation is even possible outside tertiary systems. Here we report the enantiospecific cross-coupling of cyclic sulfones and Grignard reagents. Up to 99% chirality transfer is observed despite the strong basicity of the Grignard components. In situ monitoring reveals that the cross-coupling is kinetically competitive with competing deprotonation, resulting in a highly enantioselective transformation.", "classifications": [ { "id": "Nanbo", "label": "Group Nanbo", "parent": "Tsuchiya", "type": "group" }, { "id": "Tsuchiya", "label": "Team Tsuchiya", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Roberto", "last_name": "Nolla-Saltiel", "name": null }, { "creator_type": "author", "first_name": "Zachary T.", "last_name": "Ariki", "name": null }, { "creator_type": "author", "first_name": "Stefanie", "last_name": "Schiele", "name": null }, { "creator_type": "author", "first_name": "Jana", "last_name": "Alpin", "name": null }, { "creator_type": "author", "first_name": "Yasuyo", "last_name": "Tahara", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Yokogawa", "name": null }, { "creator_type": "author", "first_name": "Masakazu", "last_name": "Nambo", "name": null }, { "creator_type": "author", "first_name": "Cathleen M.", "last_name": "Crudden", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41557-024-01594-x" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "39103655" } }, "mesh": [], "publication": { "conference_name": null, "date": "2024 Aug 5", "date_precision": "day", "issue": "", "normalized_date": "2024-08-05", "pages": "", "proceedings_title": null, "publisher": "", "title": "Nature chemistry", "volume": "", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Enantiospecific cross-coupling of cyclic alkyl sulfones.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Identifying the mechanisms of action of anticancer drugs is an important step in the development of new drugs. In this study, we established a comprehensive screening platform consisting of 68 oncogenes (MANO panel), encompassing 243 genetic variants, to identify predictive markers for drug efficacy. Validation was performed using drugs that targeted EGFR, BRAF, and MAP2K1, which confirmed the utility of this functional screening panel. Screening of a BRCA2-knockout DLD1 cell line (DLD1-KO) revealed that cells expressing SMO and GLI1 were resistant to olaparib. Gene set enrichment analysis identified genes associated with DNA damage repair that were enriched in cells overexpressing SMO and GLI1. The expression of genes associated with homologous recombination repair (HR), such as the FANC family and BRCA1/2, was significantly upregulated by GLI1 expression, which is indicative of PARP inhibitor resistance. Although not all representative genes of the nucleotide excision repair (NER) pathway were upregulated, NER activity was enhanced by GLI1. The GLI1 inhibitor was effective against DLD1-KO cells overexpressing GLI1 both in vitro and in vivo. Furthermore, the combination therapy of olaparib and GLI1 inhibitor exhibited a synergistic effect on DLD1-KO, suggesting the possible clinical application of GLI1 inhibitor targeting cancer with defective DNA damage repair. This platform enables the identification of biomarkers associated with drug sensitivity, and is a useful tool for drug development.", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Ikeuchi", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Matsuno", "name": null }, { "creator_type": "author", "first_name": "Rika", "last_name": "Kusumoto-Matsuo", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Kojima", "name": null }, { "creator_type": "author", "first_name": "Toshihide", "last_name": "Ueno", "name": null }, { "creator_type": "author", "first_name": "Masachika", "last_name": "Ikegami", "name": null }, { "creator_type": "author", "first_name": "Rina", "last_name": "Kitada", "name": null }, { "creator_type": "author", "first_name": "Hitomi", "last_name": "Sumiyoshi-Okuma", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Kojima", "name": null }, { "creator_type": "author", "first_name": "Kan", "last_name": "Yonemori", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null }, { "creator_type": "author", "first_name": "Kazuya", "last_name": "Takamochi", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Ken-Ichi", "last_name": "Yoshioka", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Mano", "name": null }, { "creator_type": "author", "first_name": "Shinji", "last_name": "Kohsaka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41388-024-03105-1" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "39095584" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "DNA Damage", "descriptor_ui": "D004249", "major_topic": true }, { "descriptor": "DNA Repair", "descriptor_ui": "D004260", "major_topic": true }, { "descriptor": "Drug Resistance, Neoplasm", "descriptor_ui": "D019008", "major_topic": true }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Phthalazines", "descriptor_ui": "D010793", "major_topic": false }, { "descriptor": "Piperazines", "descriptor_ui": "D010879", "major_topic": false }, { "descriptor": "Poly(ADP-ribose) Polymerase Inhibitors", "descriptor_ui": "D000067856", "major_topic": true }, { "descriptor": "Xenograft Model Antitumor Assays", "descriptor_ui": "D023041", "major_topic": false }, { "descriptor": "Zinc Finger Protein GLI1", "descriptor_ui": "D000071676", "major_topic": true } ], "publication": { "conference_name": null, "date": "2024 Aug 3", "date_precision": "day", "issue": "", "normalized_date": "2024-08-03", "pages": "", "proceedings_title": null, "publisher": "", "title": "Oncogene", "volume": "", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "GLI1 confers resistance to PARP inhibitors by activating the DNA damage repair pathway.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Sayaka", "last_name": "Mizutani", "name": null }, { "creator_type": "author", "first_name": "Ayako", "last_name": "Tamaki", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Shiba", "name": null }, { "creator_type": "author", "first_name": "Felix", "last_name": "Salim", "name": null }, { "creator_type": "author", "first_name": "Masayoshi", "last_name": "Yamada", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Takamaru", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Nakajima", "name": null }, { "creator_type": "author", "first_name": "Naohisa", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Shoko", "last_name": "Ikuta", "name": null }, { "creator_type": "author", "first_name": "Tatsuo", "last_name": "Yachida", "name": null }, { "creator_type": "author", "first_name": "Tatsuhiro", "last_name": "Shibata", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Yutaka", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Shinji", "last_name": "Fukuda", "name": null }, { "creator_type": "author", "first_name": "Hideki", "last_name": "Ishikawa", "name": null }, { "creator_type": "author", "first_name": "Takuji", "last_name": "Yamada", "name": null }, { "creator_type": "author", "first_name": "Shinichi", "last_name": "Yachida", "name": null } ], "identifiers": { "doi": { "normalized": "10.1136/gutjnl-2024-332381" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "39089862" } }, "mesh": [], "publication": { "conference_name": null, "date": "2024 Aug 1", "date_precision": "day", "issue": "", "normalized_date": "2024-08-01", "pages": "gutjnl-2024-332381", "proceedings_title": null, "publisher": "", "title": "Gut", "volume": "", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Dynamics of the gut microbiome in FAP patients undergoing intensive endoscopic reduction of polyp burden.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "A highly sensitive method is proposed for obtaining the Raman spectra of low-concentration proteins and nucleic acids in an aqueous solution using liquid-liquid phase separation. This method uses water droplets formed by adding a large amount of polyethylene glycol into a biomolecular aqueous solution. Ordinary spontaneous Raman spectra are obtained with a high signal-to-noise ratio.", "classifications": [ { "id": "Nakabayashi", "label": "Group Nakabayashi", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Reona", "last_name": "Tobita", "name": null }, { "creator_type": "author", "first_name": "Lisa", "last_name": "Kageyama", "name": null }, { "creator_type": "author", "first_name": "Ayaka", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Tahara", "name": null }, { "creator_type": "author", "first_name": "Shinji", "last_name": "Kajimoto", "name": null }, { "creator_type": "author", "first_name": "Takakazu", "last_name": "Nakabayashi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1039/d4cc03035d" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "39072433" } }, "mesh": [ { "descriptor": "Phase Separation", "descriptor_ui": "D000095496", "major_topic": false }, { "descriptor": "Polyethylene Glycols", "descriptor_ui": "D011092", "major_topic": true }, { "descriptor": "Proteins", "descriptor_ui": "D011506", "major_topic": true }, { "descriptor": "Signal-To-Noise Ratio", "descriptor_ui": "D059629", "major_topic": false }, { "descriptor": "Solutions", "descriptor_ui": "D012996", "major_topic": true }, { "descriptor": "Spectrum Analysis, Raman", "descriptor_ui": "D013059", "major_topic": true }, { "descriptor": "Water", "descriptor_ui": "D014867", "major_topic": true } ], "publication": { "conference_name": null, "date": "2024 Jul 29", "date_precision": "day", "issue": "", "normalized_date": "2024-07-29", "pages": "", "proceedings_title": null, "publisher": "", "title": "Chemical communications (Cambridge, England)", "volume": "", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Highly sensitive Raman measurements of protein aqueous solutions using liquid-liquid phase separation.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The UPPS-P Impulsive Behavior Model and the various psychometric instruments developed and validated based on this model are well established in clinical and research settings. However, evidence regarding the psychometric validity, reliability, and equivalence across multiple countries of residence, languages, or gender identities, including gender-diverse individuals, is lacking to date. Using data from the International Sex Survey (N = 82,243), confirmatory factor analyses and measurement invariance analyses were performed on the preestablished five-factor structure of the 20-item short version of the UPPS-P Impulsive Behavior Scale to examine whether (a) psychometric validity and reliability and (b) psychometric equivalence hold across 34 country-of-residence-related, 22 language-related, and three gender-identity-related groups. The results of the present study extend the latter psychometric instrument's well-established relevance to 26 countries, 13 languages, and three gender identities. Most notably, psychometric validity and reliability were evidenced across nine novel translations included in the present study (i.e., Croatian, English, German, Hebrew, Korean, Macedonian, Polish, Portuguese-Portugal, and Spanish-Latin American) and psychometric equivalence was evidenced across all three gender identities included in the present study (i.e., women, men, and gender-diverse individuals).", "classifications": [ { "id": "Fujiwara", "label": "Group Fujiwara", "parent": "Fujiwara", "type": "group" }, { "id": "Fujiwara", "label": "Team Fujiwara", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Lois", "last_name": "Fournier", "name": null }, { "creator_type": "author", "first_name": "Beata", "last_name": "Bothe", "name": null }, { "creator_type": "author", "first_name": "Zsolt", "last_name": "Demetrovics", "name": null }, { "creator_type": "author", "first_name": "Monika", "last_name": "Koos", "name": null }, { "creator_type": "author", "first_name": "Shane W.", "last_name": "Kraus", "name": null }, { "creator_type": "author", "first_name": "Lena", "last_name": "Nagy", "name": null }, { "creator_type": "author", "first_name": "Marc N.", "last_name": "Potenza", "name": null }, { "creator_type": "author", "first_name": "Rafael", "last_name": "Ballester-Arnal", "name": null }, { "creator_type": "author", "first_name": "Dominik", "last_name": "Batthyany", "name": null }, { "creator_type": "author", "first_name": "Sophie", "last_name": "Bergeron", "name": null }, { "creator_type": "author", "first_name": "Peer", "last_name": "Briken", "name": null }, { "creator_type": "author", "first_name": "Julius", "last_name": "Burkauskas", "name": null }, { "creator_type": "author", "first_name": "Georgina", "last_name": "Cardenas-Lopez", "name": null }, { "creator_type": "author", "first_name": "Joana", "last_name": "Carvalho", "name": null }, { "creator_type": "author", "first_name": "Jesus", "last_name": "Castro-Calvo", "name": null }, { "creator_type": "author", "first_name": "Lijun", "last_name": "Chen", "name": null }, { "creator_type": "author", "first_name": "Giacomo", "last_name": "Ciocca", "name": null }, { "creator_type": "author", "first_name": "Ornella", "last_name": "Corazza", "name": null }, { "creator_type": "author", "first_name": "Rita I.", "last_name": "Csako", "name": null }, { "creator_type": "author", "first_name": "David P.", "last_name": "Fernandez", "name": null }, { "creator_type": "author", "first_name": "Hironobu", "last_name": "Fujiwara", "name": null }, { "creator_type": "author", "first_name": "Elaine F.", "last_name": "Fernandez", "name": null }, { "creator_type": "author", "first_name": "Johannes", "last_name": "Fuss", "name": null }, { "creator_type": "author", "first_name": "Roman", "last_name": "Gabrhelik", "name": null }, { "creator_type": "author", "first_name": "Ateret", "last_name": "Gewirtz-Meydan", "name": null }, { "creator_type": "author", "first_name": "Biljana", "last_name": "Gjoneska", "name": null }, { "creator_type": "author", "first_name": "Mateusz", "last_name": "Gola", "name": null }, { "creator_type": "author", "first_name": "Joshua B.", "last_name": "Grubbs", "name": null }, { "creator_type": "author", "first_name": "Hashim T.", "last_name": "Hashim", "name": null }, { "creator_type": "author", "first_name": "Md", "last_name": "Saiful Islam", "name": null }, { "creator_type": "author", "first_name": "Mustafa", "last_name": "Ismail", "name": null }, { "creator_type": "author", "first_name": "Martha C.", "last_name": "Jimenez-Martinez", "name": null }, { "creator_type": "author", "first_name": "Tanja", "last_name": "Jurin", "name": null }, { "creator_type": "author", "first_name": "Ondrej", "last_name": "Kalina", "name": null }, { "creator_type": "author", "first_name": "Verena", "last_name": "Klein", "name": null }, { "creator_type": "author", "first_name": "Andras", "last_name": "Kolto", "name": null }, { "creator_type": "author", "first_name": "Sang-Kyu", "last_name": "Lee", "name": null }, { "creator_type": "author", "first_name": "Karol", "last_name": "Lewczuk", "name": null }, { "creator_type": "author", "first_name": "Chung-Ying", "last_name": "Lin", "name": null }, { "creator_type": "author", "first_name": "Christine", "last_name": "Lochner", "name": null }, { "creator_type": "author", "first_name": "Silvia", "last_name": "Lopez-Alvarado", "name": null }, { "creator_type": "author", "first_name": "Katerina", "last_name": "Lukavska", "name": null }, { "creator_type": "author", "first_name": "Percy", "last_name": "Mayta-Tristan", "name": null }, { "creator_type": "author", "first_name": "Dan J.", "last_name": "Miller", "name": null }, { "creator_type": "author", "first_name": "Olga", "last_name": "Orosova", "name": null }, { "creator_type": "author", "first_name": "Gabor", "last_name": "Orosz", "name": null }, { "creator_type": "author", "first_name": "Fernando P.", "last_name": "Ponce", "name": null }, { "creator_type": "author", "first_name": "Gonzalo R.", "last_name": "Quintana", "name": null }, { "creator_type": "author", "first_name": "Gabriel C.", "last_name": "Quintero Garzola", "name": null }, { "creator_type": "author", "first_name": "Jano", "last_name": "Ramos-Diaz", "name": null }, { "creator_type": "author", "first_name": "Kevin", "last_name": "Rigaud", "name": null }, { "creator_type": "author", "first_name": "Ann", "last_name": "Rousseau", "name": null }, { "creator_type": "author", "first_name": "Marco", "last_name": "De Tubino Scanavino", "name": null }, { "creator_type": "author", "first_name": "Marion K.", "last_name": "Schulmeyer", "name": null }, { "creator_type": "author", "first_name": "Pratap", "last_name": "Sharan", "name": null }, { "creator_type": "author", "first_name": "Mami", "last_name": "Shibata", "name": null }, { "creator_type": "author", "first_name": "Sheikh", "last_name": "Shoib", "name": null }, { "creator_type": "author", "first_name": "Vera", "last_name": "Sigre-Leiros", "name": null }, { "creator_type": "author", "first_name": "Luke", "last_name": "Sniewski", "name": null }, { "creator_type": "author", "first_name": "Ognen", "last_name": "Spasovski", "name": null }, { "creator_type": "author", "first_name": "Vesta", "last_name": "Steibliene", "name": null }, { "creator_type": "author", "first_name": "Dan J.", "last_name": "Stein", "name": null }, { "creator_type": "author", "first_name": "Julian", "last_name": "Strizek", "name": null }, { "creator_type": "author", "first_name": "Meng-Che", "last_name": "Tsai", "name": null }, { "creator_type": "author", "first_name": "Berk C.", "last_name": "Unsal", "name": null }, { "creator_type": "author", "first_name": "Marie-Pier", "last_name": "Vaillancourt-Morel", "name": null }, { "creator_type": "author", "first_name": "Marie Claire", "last_name": "Van Hout", "name": null }, { "creator_type": "author", "first_name": "Joel", "last_name": "Billieux", "name": null } ], "identifiers": { "doi": { "normalized": "10.1177/10731911241259560" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "39054862" } }, "mesh": [ { "descriptor": "Adolescent", "descriptor_ui": "D000293", "major_topic": false }, { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Cross-Cultural Comparison", "descriptor_ui": "D003431", "major_topic": false }, { "descriptor": "Factor Analysis, Statistical", "descriptor_ui": "D005163", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Gender Identity", "descriptor_ui": "D005783", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Impulsive Behavior", "descriptor_ui": "D007175", "major_topic": true }, { "descriptor": "Language", "descriptor_ui": "D007802", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Psychometrics", "descriptor_ui": "D011594", "major_topic": false }, { "descriptor": "Reproducibility of Results", "descriptor_ui": "D015203", "major_topic": false }, { "descriptor": "Surveys and Questionnaires", "descriptor_ui": "D011795", "major_topic": false }, { "descriptor": "Young Adult", "descriptor_ui": "D055815", "major_topic": false } ], "publication": { "conference_name": null, "date": "2024 Jul 26", "date_precision": "day", "issue": "", "normalized_date": "2024-07-26", "pages": "10731911241259560", "proceedings_title": null, "publisher": "", "title": "Assessment", "volume": "", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Evaluating the factor structure and measurement invariance of the 20-item short version of the UPPS-P Impulsive Behavior Scale across multiple countries, languages, and gender identities.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Ectodermal organs, such as hair follicles, originate from simple epithelial and mesenchymal sheets through a complex developmental process driven by interactions between these cell types. This process involves dermal condensation, placode formation, bud morphogenesis, and organogenesis, and all of these processes require intricate interactions among various tissues. Recent research has emphasized the crucial role of reciprocal and dynamic interactions between cells and the extracellular matrix (ECM), referred to as the \"dynamic duo\", in the development of ectodermal organs. These interactions provide spatially and temporally changing biophysical and biochemical cues within tissues. Using the hair follicle as an example, this review highlights two types of cell-ECM adhesion units-focal adhesion-type and hemidesmosome-type adhesion units-that facilitate communication between epithelial and mesenchymal cells. This review further explores how these adhesion units, along with other cell-ECM interactions, evolve during hair follicle development and regeneration, underscoring their importance in guiding both developmental and regenerative processes.", "classifications": [ { "id": "Fujiwara", "label": "Group Fujiwara", "parent": "Fujiwara", "type": "group" }, { "id": "Fujiwara", "label": "Team Fujiwara", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Hironobu", "last_name": "Fujiwara", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.ydbio.2024.07.012" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "39059679" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Adhesion", "descriptor_ui": "D002448", "major_topic": false }, { "descriptor": "Cell Communication", "descriptor_ui": "D002450", "major_topic": false }, { "descriptor": "Epithelial Cells", "descriptor_ui": "D004847", "major_topic": false }, { "descriptor": "Extracellular Matrix", "descriptor_ui": "D005109", "major_topic": true }, { "descriptor": "Focal Adhesions", "descriptor_ui": "D022001", "major_topic": false }, { "descriptor": "Hair Follicle", "descriptor_ui": "D018859", "major_topic": true }, { "descriptor": "Hemidesmosomes", "descriptor_ui": "D022002", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Regeneration", "descriptor_ui": "D012038", "major_topic": true } ], "publication": { "conference_name": null, "date": "2024 Jul 24", "date_precision": "day", "issue": "", "normalized_date": "2024-07-24", "pages": "S0012-1606(24)00192-1", "proceedings_title": null, "publisher": "", "title": "Developmental biology", "volume": "", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Dynamic duo: Cell-extracellular matrix interactions in hair follicle development and regeneration.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Pulmonary tumor thrombotic microangiopathy (PTTM) is a rapidly progressive cancer-related disease with a dismal clinical course. The patient in this report was a 43-year-old man with metastatic salivary duct carcinoma arising from the parotid gland. Combined androgen blockade therapy was administered started as first-line treatment, but failed after 5 months, followed by docetaxel plus carboplatin therapy as second-line treatment, which failed after 3 months. Genomic profiling revealed a BRAF V600E mutation, and combined BRAF and MEK inhibitor therapy was started as third-line treatment. The cancer remained stable during the first 10 months of third-line treatment, but treatment was subsequently discontinued due to the onset of symptoms of fatigue, myalgia and arthritis. Twenty days after the onset of these symptoms and interruption of third-line treatment, the patient was urgently admitted to hospital with respiratory distress and severe thrombocytopenia. CT images at the time of admission led our radiologist to the possibility of PTTM, but the patient died the day after admission and autopsy findings indicated that PTTM was the cause of death. This report describes a very informative case of PTTM with sequential imaging and detailed autopsy findings were available and provides a literature review.", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Mai", "last_name": "Itoyama", "name": null }, { "creator_type": "author", "first_name": "Akihiro", "last_name": "Ohara", "name": null }, { "creator_type": "author", "first_name": "Kazuki", "last_name": "Yokoyama", "name": null }, { "creator_type": "author", "first_name": "Shun", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Ken", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Yuichiro", "last_name": "Tada", "name": null }, { "creator_type": "author", "first_name": "Ayumi", "last_name": "Sugitani", "name": null }, { "creator_type": "author", "first_name": "Hirokazu", "last_name": "Sugino", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null }, { "creator_type": "author", "first_name": "Masahiko", "last_name": "Kusumoto", "name": null }, { "creator_type": "author", "first_name": "Kenichi", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Yoshitaka", "last_name": "Honma", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.anl.2024.07.002" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "39047424" } }, "mesh": [ { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Androgen Antagonists", "descriptor_ui": "D000726", "major_topic": false }, { "descriptor": "Antineoplastic Combined Chemotherapy Protocols", "descriptor_ui": "D000971", "major_topic": true }, { "descriptor": "Autopsy", "descriptor_ui": "D001344", "major_topic": false }, { "descriptor": "Carboplatin", "descriptor_ui": "D016190", "major_topic": false }, { "descriptor": "Carcinoma, Ductal", "descriptor_ui": "D044584", "major_topic": false }, { "descriptor": "Docetaxel", "descriptor_ui": "D000077143", "major_topic": false }, { "descriptor": "Fatal Outcome", "descriptor_ui": "D017809", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Lung Neoplasms", "descriptor_ui": "D008175", "major_topic": true }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Parotid Neoplasms", "descriptor_ui": "D010307", "major_topic": true }, { "descriptor": "Proto-Oncogene Proteins B-raf", "descriptor_ui": "D048493", "major_topic": false }, { "descriptor": "Salivary Ducts", "descriptor_ui": "D018987", "major_topic": false }, { "descriptor": "Thrombocytopenia", "descriptor_ui": "D013921", "major_topic": false }, { "descriptor": "Thrombotic Microangiopathies", "descriptor_ui": "D057049", "major_topic": true }, { "descriptor": "Tomography, X-Ray Computed", "descriptor_ui": "D014057", "major_topic": false } ], "publication": { "conference_name": null, "date": "2024 Jul 23", "date_precision": "day", "issue": "5", "normalized_date": "2024-07-23", "pages": "829-833", "proceedings_title": null, "publisher": "", "title": "Auris, nasus, larynx", "volume": "51", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "An autopsy case of pulmonary tumor thrombotic microangiopathy that developed during chemotherapy for salivary duct carcinoma of the parotid gland.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Accumulating evidence demonstrates clear correlation between the gut microbiota and sporadic colorectal cancer (CRC). Despite this, there is limited understanding of the association between the gut microbiota and CRC in Lynch Syndrome (LS), a hereditary type of CRC. Here, we analyzed fecal shotgun metagenomic and targeted metabolomic of 71 Japanese LS subjects. A previously published Japanese sporadic CRC cohort, which includes non-LS controls, was utilized as a non-LS cohort (n = 437). LS subjects exhibited reduced microbial diversity and low-Faecalibacterium enterotypes compared to non-LS. Patients with LS-CRC had higher levels of Fusobacterium nucleatum and fap2. Differential fecal metabolites and functional genes suggest heightened degradation of lysine and arginine in LS-CRC. A comparison between LS and non-LS subjects prior to adenoma formation revealed distinct fecal metabolites of LS subjects. These findings suggest that the gut microbiota plays a more responsive role in CRC tumorigenesis in patients with LS than those without LS.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Felix", "last_name": "Salim", "name": null }, { "creator_type": "author", "first_name": "Sayaka", "last_name": "Mizutani", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Shiba", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Takamaru", "name": null }, { "creator_type": "author", "first_name": "Masayoshi", "last_name": "Yamada", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Nakajima", "name": null }, { "creator_type": "author", "first_name": "Tatsuo", "last_name": "Yachida", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Yutaka", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Shinji", "last_name": "Fukuda", "name": null }, { "creator_type": "author", "first_name": "Shinichi", "last_name": "Yachida", "name": null }, { "creator_type": "author", "first_name": "Takuji", "last_name": "Yamada", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.isci.2024.110181" }, "pmcid": { "normalized": "PMC11237946" }, "pmid": { "normalized": "38993678" } }, "mesh": [], "publication": { "conference_name": null, "date": "2024 Jul 19", "date_precision": "day", "issue": "7", "normalized_date": "2024-07-19", "pages": "110181", "proceedings_title": null, "publisher": "", "title": "iScience", "volume": "27", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Fusobacterium species are distinctly associated with patients with Lynch syndrome colorectal cancer.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Epithelial-to-mesenchymal transition (EMT) contributes to the poor prognosis of patients with cancer by promoting distant metastasis and anti-cancer drug resistance. Several distinct metabolic alterations have been identified as key EMT phenotypes. In the present study, we further characterize the role of transforming growth factor-beta (TGF-beta)-induced EMT in non-small-cell lung cancer. Our study revealed that TGF-beta plays a role in EMT functions by upregulation of cytidine 5'-triphosphate synthetase 1 (CTPS), a vital enzyme for CTP biosynthesis in the pyrimidine metabolic pathway. Both knockdown and enzymatic inhibition of CTPS reduced TGF-beta-induced changes in EMT marker expression, chemoresistance and migration in vitro. Moreover, CTPS knockdown counteracted the TGF-beta-mediated downregulation of UDP-glucuronate, glutarate, creatine, taurine and nicotinamide. These findings indicate that CTPS plays a multifaceted role in EMT metabolism, which is crucial for the malignant transformation of cancer through EMT, and underline its potential as a promising therapeutic target for preventing drug resistance and metastasis in non-small-cell lung cancer.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Fumie", "last_name": "Nakasuka", "name": null }, { "creator_type": "author", "first_name": "Akiyoshi", "last_name": "Hirayama", "name": null }, { "creator_type": "author", "first_name": "Hideki", "last_name": "Makinoshima", "name": null }, { "creator_type": "author", "first_name": "Seiji", "last_name": "Yano", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Sho", "last_name": "Tabata", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/2211-5463.13860" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "39030877" } }, "mesh": [ { "descriptor": "Carbon-Nitrogen Ligases", "descriptor_ui": "D019731", "major_topic": true }, { "descriptor": "Carcinoma, Non-Small-Cell Lung", "descriptor_ui": "D002289", "major_topic": true }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Cell Movement", "descriptor_ui": "D002465", "major_topic": false }, { "descriptor": "Drug Resistance, Neoplasm", "descriptor_ui": "D019008", "major_topic": false }, { "descriptor": "Epithelial-Mesenchymal Transition", "descriptor_ui": "D058750", "major_topic": true }, { "descriptor": "Gene Expression Regulation, Neoplastic", "descriptor_ui": "D015972", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Ligases", "descriptor_ui": "D008025", "major_topic": true }, { "descriptor": "Lung Neoplasms", "descriptor_ui": "D008175", "major_topic": true }, { "descriptor": "Transforming Growth Factor beta", "descriptor_ui": "D016212", "major_topic": false } ], "publication": { "conference_name": null, "date": "2024 Jul 19", "date_precision": "day", "issue": "", "normalized_date": "2024-07-19", "pages": "", "proceedings_title": null, "publisher": "", "title": "FEBS open bio", "volume": "", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "The role of cytidine 5'-triphosphate synthetase 1 in metabolic rewiring during epithelial-to-mesenchymal transition in non-small-cell lung cancer.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The homeostatic regulation of sleep is characterized by rebound sleep after prolonged wakefulness, but the molecular and cellular mechanisms underlying this regulation are still unknown. In this study, we show that Ca(2+)/calmodulin-dependent protein kinase II (CaMKII)-dependent activity control of parvalbumin (PV)-expressing cortical neurons is involved in homeostatic regulation of sleep in male mice. Prolonged wakefulness enhances cortical PV-neuron activity. Chemogenetic suppression or activation of cortical PV neurons inhibits or induces rebound sleep, implying that rebound sleep is dependent on increased activity of cortical PV neurons. Furthermore, we discovered that CaMKII kinase activity boosts the activity of cortical PV neurons, and that kinase activity is important for homeostatic sleep rebound. Here, we propose that CaMKII-dependent PV-neuron activity represents negative feedback inhibition of cortical neural excitability, which serves as the distributive cortical circuits for sleep homeostatic regulation.", "classifications": [ { "id": "Miyamichi", "label": "Group Miyamichi", "parent": "Enomoto", "type": "group" }, { "id": "Enomoto", "label": "Team Enomoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Kazuhiro", "last_name": "Kon", "name": null }, { "creator_type": "author", "first_name": "Koji L.", "last_name": "Ode", "name": null }, { "creator_type": "author", "first_name": "Tomoyuki", "last_name": "Mano", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Fujishima", "name": null }, { "creator_type": "author", "first_name": "Riina R.", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Tone", "name": null }, { "creator_type": "author", "first_name": "Chika", "last_name": "Shimizu", "name": null }, { "creator_type": "author", "first_name": "Shinnosuke", "last_name": "Shiono", "name": null }, { "creator_type": "author", "first_name": "Saori", "last_name": "Yada", "name": null }, { "creator_type": "author", "first_name": "Kyoko", "last_name": "Matsuzawa", "name": null }, { "creator_type": "author", "first_name": "Shota Y.", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Junko", "last_name": "Yoshida Garcon", "name": null }, { "creator_type": "author", "first_name": "Mari", "last_name": "Kaneko", "name": null }, { "creator_type": "author", "first_name": "Yuta", "last_name": "Shinohara", "name": null }, { "creator_type": "author", "first_name": "Rikuhiro G.", "last_name": "Yamada", "name": null }, { "creator_type": "author", "first_name": "Shoi", "last_name": "Shi", "name": null }, { "creator_type": "author", "first_name": "Kazunari", "last_name": "Miyamichi", "name": null }, { "creator_type": "author", "first_name": "Kenta", "last_name": "Sumiyama", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Kiyonari", "name": null }, { "creator_type": "author", "first_name": "Etsuo A.", "last_name": "Susaki", "name": null }, { "creator_type": "author", "first_name": "Hiroki R.", "last_name": "Ueda", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41467-024-50168-5" }, "pmcid": { "normalized": "PMC11258272" }, "pmid": { "normalized": "39025867" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Calcium-Calmodulin-Dependent Protein Kinase Type 2", "descriptor_ui": "D054732", "major_topic": true }, { "descriptor": "Cerebral Cortex", "descriptor_ui": "D002540", "major_topic": true }, { "descriptor": "Homeostasis", "descriptor_ui": "D006706", "major_topic": true }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Transgenic", "descriptor_ui": "D008822", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": true }, { "descriptor": "Parvalbumins", "descriptor_ui": "D010320", "major_topic": true }, { "descriptor": "Sleep", "descriptor_ui": "D012890", "major_topic": true }, { "descriptor": "Wakefulness", "descriptor_ui": "D014851", "major_topic": true } ], "publication": { "conference_name": null, "date": "2024 Jul 18", "date_precision": "day", "issue": "1", "normalized_date": "2024-07-18", "pages": "6054", "proceedings_title": null, "publisher": "", "title": "Nature communications", "volume": "15", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Cortical parvalbumin neurons are responsible for homeostatic sleep rebound through CaMKII activation.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Predicting olfactory perceptions from odorant molecules is challenging due to the complex and potentially discontinuous nature of the perceptual space for smells. In this study, we introduce a deep learning model, Mol-PECO (Molecular Representation by Positional Encoding of Coulomb Matrix), designed to predict olfactory perceptions based on molecular structures and electrostatics. Mol-PECO learns the efficient embedding of molecules by utilizing the Coulomb matrix, which encodes atomic coordinates and charges, as an alternative of the adjacency matrix and its Laplacian eigenfunctions as positional encoding of atoms. With a comprehensive dataset of odor molecules and descriptors, Mol-PECO outperforms traditional machine learning methods using molecular fingerprints and graph neural networks based on adjacency matrices. The learned embeddings by Mol-PECO effectively capture the odor space, enabling global clustering of descriptors and local retrieval of similar odorants. This work contributes to a deeper understanding of the olfactory sense and its mechanisms.", "classifications": [ { "id": "Kobayashi", "label": "Group Kobayashi", "parent": "Wakamoto", "type": "group" }, { "id": "Wakamoto", "label": "Team Wakamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Mengji", "last_name": "Zhang", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Hiki", "name": null }, { "creator_type": "author", "first_name": "Akira", "last_name": "Funahashi", "name": null }, { "creator_type": "author", "first_name": "Tetsuya J.", "last_name": "Kobayashi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41540-024-00401-0" }, "pmcid": { "normalized": "PMC11255234" }, "pmid": { "normalized": "39019918" } }, "mesh": [ { "descriptor": "Algorithms", "descriptor_ui": "D000465", "major_topic": false }, { "descriptor": "Deep Learning", "descriptor_ui": "D000077321", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Machine Learning", "descriptor_ui": "D000069550", "major_topic": false }, { "descriptor": "Molecular Structure", "descriptor_ui": "D015394", "major_topic": false }, { "descriptor": "Neural Networks, Computer", "descriptor_ui": "D016571", "major_topic": false }, { "descriptor": "Odorants", "descriptor_ui": "D009812", "major_topic": true }, { "descriptor": "Olfactory Perception", "descriptor_ui": "D055696", "major_topic": true }, { "descriptor": "Smell", "descriptor_ui": "D012903", "major_topic": false }, { "descriptor": "Static Electricity", "descriptor_ui": "D055672", "major_topic": true } ], "publication": { "conference_name": null, "date": "2024 Jul 17", "date_precision": "day", "issue": "1", "normalized_date": "2024-07-17", "pages": "76", "proceedings_title": null, "publisher": "", "title": "NPJ systems biology and applications", "volume": "10", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "A deep position-encoding model for predicting olfactory perception from molecular structures and electrostatics.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Gut bacteria are linked to neurodegenerative diseases but the risk factors beyond microbiota composition are limited. Here we used a pre-clinical model of multiple sclerosis (MS), experimental autoimmune encephalomyelitis (EAE), to identify microbial risk factors. Mice with different genotypes and complex microbiotas or six combinations of a synthetic human microbiota were analysed, resulting in varying probabilities of severe neuroinflammation. However, the presence or relative abundances of suspected microbial risk factors failed to predict disease severity. Akkermansia muciniphila, often associated with MS, exhibited variable associations with EAE severity depending on the background microbiota. Significant inter-individual disease course variations were observed among mice harbouring the same microbiota. Evaluation of microbial functional characteristics and host immune responses demonstrated that the immunoglobulin A coating index of certain bacteria before disease onset is a robust individualized predictor of disease development. Our study highlights the need to consider microbial community networks and host-specific bidirectional interactions when aiming to predict severity of neuroinflammation.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Alex", "last_name": "Steimle", "name": null }, { "creator_type": "author", "first_name": "Mareike", "last_name": "Neumann", "name": null }, { "creator_type": "author", "first_name": "Erica T.", "last_name": "Grant", "name": null }, { "creator_type": "author", "first_name": "Stephanie", "last_name": "Willieme", "name": null }, { "creator_type": "author", "first_name": "Alessandro", "last_name": "De Sciscio", "name": null }, { "creator_type": "author", "first_name": "Amy", "last_name": "Parrish", "name": null }, { "creator_type": "author", "first_name": "Markus", "last_name": "Ollert", "name": null }, { "creator_type": "author", "first_name": "Eiji", "last_name": "Miyauchi", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Shinji", "last_name": "Fukuda", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Ohno", "name": null }, { "creator_type": "author", "first_name": "Mahesh S.", "last_name": "Desai", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41564-024-01761-3" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "39009690" } }, "mesh": [ { "descriptor": "Akkermansia", "descriptor_ui": "D000086102", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Bacteria", "descriptor_ui": "D001419", "major_topic": false }, { "descriptor": "Disease Models, Animal", "descriptor_ui": "D004195", "major_topic": true }, { "descriptor": "Encephalomyelitis, Autoimmune, Experimental", "descriptor_ui": "D004681", "major_topic": true }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Gastrointestinal Microbiome", "descriptor_ui": "D000069196", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Immunoglobulin A", "descriptor_ui": "D007070", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Multiple Sclerosis", "descriptor_ui": "D009103", "major_topic": true }, { "descriptor": "Risk Factors", "descriptor_ui": "D012307", "major_topic": false }, { "descriptor": "Severity of Illness Index", "descriptor_ui": "D012720", "major_topic": false } ], "publication": { "conference_name": null, "date": "2024 Jul 15", "date_precision": "day", "issue": "", "normalized_date": "2024-07-15", "pages": "", "proceedings_title": null, "publisher": "", "title": "Nature microbiology", "volume": "", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Gut microbial factors predict disease severity in a mouse model of multiple sclerosis.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Polycyclic aromatic hydrocarbons (PAHs) are fragments of graphene that have attracted considerable attention as a new class of carbon-based materials. The functionalization of edge positions in PAHs is important to enable the modulation of physical and chemical properties essential for various applications. However, straightforward methods that combine functional group tolerance and regioselectivity remain sought after. Here we report a photochemical approach for the direct alkylation of carbon-hydrogen bonds in PAHs that takes place in a regiospecific manner, an outcome that has never been achieved in related thermal reactions. A reaction mechanism involving a single electron transfer process from photo-excited PAHs to sulfones, and a rationale for the origin of regioselectivity are proposed on the basis of spectroscopic analyses and theoretical calculations.", "classifications": [ { "id": "Nanbo", "label": "Group Nanbo", "parent": "Tsuchiya", "type": "group" }, { "id": "Tsuchiya", "label": "Team Tsuchiya", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Motoo", "last_name": "Ohtsuka", "name": null }, { "creator_type": "author", "first_name": "Koushik", "last_name": "Ghosh", "name": null }, { "creator_type": "author", "first_name": "Jacky C.-H.", "last_name": "Yim", "name": null }, { "creator_type": "author", "first_name": "Hikaru", "last_name": "Sotome", "name": null }, { "creator_type": "author", "first_name": "Tsubasa", "last_name": "Okamoto", "name": null }, { "creator_type": "author", "first_name": "Kayo", "last_name": "Suda", "name": null }, { "creator_type": "author", "first_name": "Yasuhiro", "last_name": "Kobori", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Yokogawa", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Miyasaka", "name": null }, { "creator_type": "author", "first_name": "Cathleen M.", "last_name": "Crudden", "name": null }, { "creator_type": "author", "first_name": "Masakazu", "last_name": "Nambo", "name": null } ], "identifiers": { "doi": { "normalized": "10.1039/d4sc02577f" }, "pmcid": { "normalized": "PMC11234832" }, "pmid": { "normalized": "38994431" } }, "mesh": [], "publication": { "conference_name": null, "date": "2024 Jul 10", "date_precision": "day", "issue": "27", "normalized_date": "2024-07-10", "pages": "10592-10599", "proceedings_title": null, "publisher": "", "title": "Chemical science", "volume": "15", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Visible-light-induced direct C-H alkylation of polycyclic aromatic hydrocarbons with alkylsulfones.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND AND PURPOSE: Maintaining mitochondrial quality is attracting attention as a new strategy to treat diabetes and diabetic complications. We previously reported that mitochondrial hyperfission by forming a protein complex between dynamin-related protein (Drp) 1 and filamin, mediates chronic heart failure and cilnidipine, initially developed as an L/N-type Ca(2+) channel blocker, improves heart failure by inhibiting Drp1-filamin protein complex. We investigated whether cilnidipine improves hyperglycaemia of various diabetic mice models. EXPERIMENTAL APPROACH: Retrospective analysis focusing on haemoglobin A1c (HbA1c) was performed in hypertensive and hyperglycaemic patients taking cilnidipine and amlodipine. After developing diabetic mice by streptozotocin (STZ) treatment, an osmotic pump including drug was implanted intraperitoneally, followed by weekly measurements of blood glucose levels. Mitochondrial morphology was analysed by electron microscopy. A Ca(2+) channel-insensitive cilnidipine derivative (1,4-dihydropyridine [DHP]) was synthesized and its pharmacological effect was evaluated using obese (ob/ob) mice fed with high-fat diet (HFD). KEY RESULTS: In patients, cilnidipine was superior to amlodipine in HbA1c lowering effect. Cilnidipine treatment improved systemic hyperglycaemia and mitochondrial morphological abnormalities in STZ-exposed mice, without lowering blood pressure. Cilnidipine failed to improve hyperglycaemia of ob/ob mice, with suppressing insulin secretion. 1,4-DHP improved hyperglycaemia and mitochondria abnormality in ob/ob mice fed HFD. 1,4-DHP and cilnidipine improved basal oxygen consumption rate of HepG2 cells cultured under 25 mM glucose. CONCLUSION AND IMPLICATIONS: Inhibition of Drp1-filamin protein complex formation becomes a new strategy for type 2 diabetes treatment.", "classifications": [ { "id": "JPMJCR2024", "label": "JPMJCR2024", "researcher": "Motohiro Nishida", "type": "grant" }, { "id": "Nishida", "label": "Group Nishida", "parent": "Nishida", "type": "group" }, { "id": "Nishimura", "label": "Group Nishimura", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yuri", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Kohei", "last_name": "Ariyoshi", "name": null }, { "creator_type": "author", "first_name": "Yasunobu", "last_name": "Nohara", "name": null }, { "creator_type": "author", "first_name": "Naoya", "last_name": "Matsunaga", "name": null }, { "creator_type": "author", "first_name": "Tsukasa", "last_name": "Shimauchi", "name": null }, { "creator_type": "author", "first_name": "Naoya", "last_name": "Shindo", "name": null }, { "creator_type": "author", "first_name": "Akiyuki", "last_name": "Nishimura", "name": null }, { "creator_type": "author", "first_name": "Xinya", "last_name": "Mi", "name": null }, { "creator_type": "author", "first_name": "Sang Geon", "last_name": "Kim", "name": null }, { "creator_type": "author", "first_name": "Tomomi", "last_name": "Ide", "name": null }, { "creator_type": "author", "first_name": "Eiji", "last_name": "Kawanishi", "name": null }, { "creator_type": "author", "first_name": "Akio", "last_name": "Ojida", "name": null }, { "creator_type": "author", "first_name": "Naoki", "last_name": "Nakashima", "name": null }, { "creator_type": "author", "first_name": "Yasuo", "last_name": "Mori", "name": null }, { "creator_type": "author", "first_name": "Motohiro", "last_name": "Nishida", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/bph.16487" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "38986570" } }, "mesh": [ { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Amlodipine", "descriptor_ui": "D017311", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Blood Glucose", "descriptor_ui": "D001786", "major_topic": false }, { "descriptor": "Calcium Channel Blockers", "descriptor_ui": "D002121", "major_topic": false }, { "descriptor": "Diabetes Mellitus, Experimental", "descriptor_ui": "D003921", "major_topic": true }, { "descriptor": "Dihydropyridines", "descriptor_ui": "D004095", "major_topic": true }, { "descriptor": "Dynamins", "descriptor_ui": "D034281", "major_topic": true }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Glucose", "descriptor_ui": "D005947", "major_topic": false }, { "descriptor": "Glycated Hemoglobin", "descriptor_ui": "D006442", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Hyperglycemia", "descriptor_ui": "D006943", "major_topic": false }, { "descriptor": "Hypertension", "descriptor_ui": "D006973", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Obese", "descriptor_ui": "D008820", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Mitochondria", "descriptor_ui": "D008928", "major_topic": false }, { "descriptor": "Retrospective Studies", "descriptor_ui": "D012189", "major_topic": false } ], "publication": { "conference_name": null, "date": "2024 Jul 10", "date_precision": "day", "issue": "", "normalized_date": "2024-07-10", "pages": "", "proceedings_title": null, "publisher": "", "title": "British journal of pharmacology", "volume": "", "year": 2024 }, "ssbd": { "database": [], "repository": [ "ssbd-repos-000424" ] }, "title": "Inhibition of dynamin-related protein 1-filamin interaction improves systemic glucose metabolism.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Oxygen molecules accept electrons from the respiratory chain in the mitochondria and are responsible for energy production in aerobic organisms. The reactive oxygen species formed via these oxygen reduction processes undergo complicated electron transfer reactions with other biological substances, which leads to alterations in their physiological functions and cause diverse biological and pathophysiological consequences (e.g., oxidative stress). Oxygen accounts for only a small proportion of the redox reactions in organisms, especially under aerobic or hypoxic conditions but not under anaerobic and hypoxic conditions. This article discusses a completely new concept of redox biology, which is governed by redox-active supersulfides, i.e., sulfur-catenated molecular species. These species are present in abundance in all organisms but remain largely unexplored in terms of redox biology and life science research. In fact, accumulating evidence shows that supersulfides have extensive redox chemical properties and that they can be readily ionized or radicalized to participate in energy metabolism, redox signaling, and oxidative stress responses in cells and in vivo. Thus, pharmacological intervention and medicinal modulation of supersulfide activities have been shown to benefit the regulation of disease pathogenesis as well as disease control.", "classifications": [ { "id": "JPMJCR2024", "label": "JPMJCR2024", "researcher": "Motohiro Nishida", "type": "grant" }, { "id": "Akaike", "label": "Group Akaike", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Group Nishida", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Takaaki", "last_name": "Akaike", "name": null }, { "creator_type": "author", "first_name": "Masanobu", "last_name": "Morita", "name": null }, { "creator_type": "author", "first_name": "Seiryo", "last_name": "Ogata", "name": null }, { "creator_type": "author", "first_name": "Jun", "last_name": "Yoshitake", "name": null }, { "creator_type": "author", "first_name": "Minkyung", "last_name": "Jung", "name": null }, { "creator_type": "author", "first_name": "Hiroki", "last_name": "Sekine", "name": null }, { "creator_type": "author", "first_name": "Hozumi", "last_name": "Motohashi", "name": null }, { "creator_type": "author", "first_name": "Uladzimir", "last_name": "Barayeu", "name": null }, { "creator_type": "author", "first_name": "Tetsuro", "last_name": "Matsunaga", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.freeradbiomed.2024.07.007" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "38992395" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Energy Metabolism", "descriptor_ui": "D004734", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mitochondria", "descriptor_ui": "D008928", "major_topic": false }, { "descriptor": "Oxidation-Reduction", "descriptor_ui": "D010084", "major_topic": true }, { "descriptor": "Oxidative Stress", "descriptor_ui": "D018384", "major_topic": true }, { "descriptor": "Reactive Oxygen Species", "descriptor_ui": "D017382", "major_topic": true }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": true }, { "descriptor": "Sulfides", "descriptor_ui": "D013440", "major_topic": true } ], "publication": { "conference_name": null, "date": "2024 Jul 9", "date_precision": "day", "issue": "", "normalized_date": "2024-07-09", "pages": "539-551", "proceedings_title": null, "publisher": "", "title": "Free radical biology & medicine", "volume": "222", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "New aspects of redox signaling mediated by supersulfides in health and disease.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Polyhalogenated molecules are often found as bioactive compounds in nature and are used as synthetic building blocks. Fluoroalkyl compounds hold promise for the development of novel pharmaceuticals and agrochemicals, as the introduction of fluoroalkyl groups is known to improve lipophilicity, membrane permeability, and metabolic stability. Three-component 1,2-halo-halodifluoromethylation reactions of alkenes are useful for their synthesis. However, general methods enabling the introduction of halodifluoromethyl (CF2X) and halogen (X') groups in the desired combination of X and X' are lacking. To address this gap, for the first time, we report a three-component halo-halodifluoromethylation of alkenes and alkynes using combinations of commercially available fluorinated carboxylic anhydrides ((CF2XCO)2O, X = Cl and Br) and alkali metal halides (X' = Cl and Br). In situ prepared fluorinated diacyl peroxides were identified as important intermediates, and the use of appropriate bipyridyl-based ligands and a copper catalyst was essential for achieving high product selectivity. The synthetic utility of the polyhalogenated products was demonstrated by exploiting differences in the reactivities of their C-X and C-X' bonds to achieve selective derivatization. Finally, the reaction mechanism and ligand effect were investigated using experimental and theoretical methods to provide important insights for the further development of catalytic reactions.", "classifications": [ { "id": "Sodeoka", "label": "Group Sodeoka", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Subrata", "last_name": "Mukherjee", "name": null }, { "creator_type": "author", "first_name": "Yuma", "last_name": "Aoki", "name": null }, { "creator_type": "author", "first_name": "Shintaro", "last_name": "Kawamura", "name": null }, { "creator_type": "author", "first_name": "Mikiko", "last_name": "Sodeoka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/anie.202407150" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "38979689" } }, "mesh": [], "publication": { "conference_name": null, "date": "2024 Jul 9", "date_precision": "day", "issue": "", "normalized_date": "2024-07-09", "pages": "e202407150", "proceedings_title": null, "publisher": "", "title": "Angewandte Chemie (International ed. in English)", "volume": "", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Ligand-Controlled Copper-Catalyzed Halo-Halodifluoromethylation of Alkenes and Alkynes Using Fluorinated Carboxylic Anhydrides.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "CIC-rearranged sarcoma is an aggressive round cell sarcoma, and an alternative ATXN1/ATXN1L fusion has been reported. Diagnosis may be difficult, and molecular assays may suffer from imperfect sensitivity. Characteristic histology and ETV4 immunohistochemical positivity are diagnostically helpful. However, ETV4 staining is unavailable in most laboratories. Here, we explored the diagnostic utility of MUC5AC immunohistochemistry in CIC-rearranged sarcomas. All 30 cases, except one, of CIC-rearranged sarcomas and 2 ATXN1-rearranged sarcomas were positive for MUC5AC, although the number of immunopositive cells was generally low (< 5%) in most samples, representing a characteristic scattered pattern. The only MUC5AC-negative case had the lowest tumor volume. Among the 110 mimicking round cell malignancies, 12 tumors showed MUC5AC positivity, including occasional cases of synovial sarcoma and small cell carcinoma, whereas the remaining 98 samples were negative. Despite its lower specificity than that of ETV4 and sparse reactivity that requires careful interpretation, MUC5AC may serve as a useful marker for CIC/ATXN1-rearranged sarcoma because of its wider accessibility.", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Shogo", "last_name": "Nishino", "name": null }, { "creator_type": "author", "first_name": "Naoki", "last_name": "Kojima", "name": null }, { "creator_type": "author", "first_name": "Hirokazu", "last_name": "Sugino", "name": null }, { "creator_type": "author", "first_name": "Taisuke", "last_name": "Mori", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null }, { "creator_type": "author", "first_name": "Akihiko", "last_name": "Yoshida", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/s00428-024-03863-z" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "38970674" } }, "mesh": [ { "descriptor": "Adolescent", "descriptor_ui": "D000293", "major_topic": false }, { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Biomarkers, Tumor", "descriptor_ui": "D014408", "major_topic": true }, { "descriptor": "Child", "descriptor_ui": "D002648", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Gene Rearrangement", "descriptor_ui": "D015321", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Immunohistochemistry", "descriptor_ui": "D007150", "major_topic": true }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Mucin 5AC", "descriptor_ui": "D055271", "major_topic": true }, { "descriptor": "Repressor Proteins", "descriptor_ui": "D012097", "major_topic": false }, { "descriptor": "Sarcoma", "descriptor_ui": "D012509", "major_topic": true }, { "descriptor": "Soft Tissue Neoplasms", "descriptor_ui": "D012983", "major_topic": false }, { "descriptor": "Young Adult", "descriptor_ui": "D055815", "major_topic": false } ], "publication": { "conference_name": null, "date": "2024 Jul 6", "date_precision": "day", "issue": "", "normalized_date": "2024-07-06", "pages": "", "proceedings_title": null, "publisher": "", "title": "Virchows Archiv : an international journal of pathology", "volume": "", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "MUC5AC immunoreactivity in scattered tumor cells is useful for diagnosing CIC-rearranged sarcoma.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Bioluminescence imaging (BLI) is an indispensable technique for visualizing the dynamics of diverse biological processes in mammalian animal models, including cancer, viral infections, and immune responses. However, a critical scientific challenge remains: non-invasively visualizing homeostatic and disease mechanisms in freely moving animals to understand the molecular basis of exercises, social behavior, and other phenomena. Classical BLI relies on prolonged camera exposure to accumulate the limited number of photons that traveled from deep tissues in anesthetized or constrained animals. Recent advancements in synthetic bioluminescence reactions, utilizing artificial luciferin-luciferase pairs, have considerably increased the number of detectable photons from deep tissues, facilitating high-speed BLI to capture moving objects. In this review, I provide an overview of emerging synthetic bioluminescence reactions that enable the non-invasive imaging of freely moving animals. This approach holds the potential to uncover unique physiological processes that are inaccessible with current methodologies.", "classifications": [ { "id": "Kuchimaru", "label": "Group Kuchimaru", "parent": "Shintaku", "type": "group" }, { "id": "Shintaku", "label": "Team Shintaku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Takahiro", "last_name": "Kuchimaru", "name": null } ], "identifiers": { "doi": { "normalized": "10.3390/ijms25137338" }, "pmcid": { "normalized": "PMC11242611" }, "pmid": { "normalized": "39000448" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Luciferases", "descriptor_ui": "D008156", "major_topic": false }, { "descriptor": "Luminescent Measurements", "descriptor_ui": "D008163", "major_topic": true } ], "publication": { "conference_name": null, "date": "2024 Jul 4", "date_precision": "day", "issue": "13", "normalized_date": "2024-07-04", "pages": "", "proceedings_title": null, "publisher": "", "title": "International journal of molecular sciences", "volume": "25", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Emerging Synthetic Bioluminescent Reactions for Non-Invasive Imaging of Freely Moving Animals.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Explainability is key to enhancing the trustworthiness of artificial intelligence in medicine. However, there exists a significant gap between physicians' expectations for model explainability and the actual behavior of these models. This gap arises from the absence of a consensus on a physician-centered evaluation framework, which is needed to quantitatively assess the practical benefits that effective explainability should offer practitioners. Here, we hypothesize that superior attention maps, as a mechanism of model explanation, should align with the information that physicians focus on, potentially reducing prediction uncertainty and increasing model reliability. We employed a multimodal transformer to predict lymph node metastasis of rectal cancer using clinical data and magnetic resonance imaging. We explored how well attention maps, visualized through a state-of-the-art technique, can achieve agreement with physician understanding. Subsequently, we compared two distinct approaches for estimating uncertainty: a standalone estimation using only the variance of prediction probability, and a human-in-the-loop estimation that considers both the variance of prediction probability and the quantified agreement. Our findings revealed no significant advantage of the human-in-the-loop approach over the standalone one. In conclusion, this case study did not confirm the anticipated benefit of the explanation in enhancing model reliability. Superficial explanations could do more harm than good by misleading physicians into relying on uncertain predictions, suggesting that the current state of attention mechanisms should not be overestimated in the context of model explainability.", "classifications": [ { "id": "Hamamoto", "label": "Group Hamamoto", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Kazuma", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Yasuyuki", "last_name": "Takamizawa", "name": null }, { "creator_type": "author", "first_name": "Mototaka", "last_name": "Miyake", "name": null }, { "creator_type": "author", "first_name": "Sono", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Lin", "last_name": "Gu", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Nakatsuka", "name": null }, { "creator_type": "author", "first_name": "Yu", "last_name": "Akagi", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Harada", "name": null }, { "creator_type": "author", "first_name": "Yukihide", "last_name": "Kanemitsu", "name": null }, { "creator_type": "author", "first_name": "Ryuji", "last_name": "Hamamoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.artmed.2024.102929" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "38996696" } }, "mesh": [ { "descriptor": "Artificial Intelligence", "descriptor_ui": "D001185", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Judgment", "descriptor_ui": "D007600", "major_topic": true }, { "descriptor": "Lymph Nodes", "descriptor_ui": "D008198", "major_topic": false }, { "descriptor": "Lymphatic Metastasis", "descriptor_ui": "D008207", "major_topic": true }, { "descriptor": "Magnetic Resonance Imaging", "descriptor_ui": "D008279", "major_topic": false }, { "descriptor": "Physicians", "descriptor_ui": "D010820", "major_topic": false }, { "descriptor": "Rectal Neoplasms", "descriptor_ui": "D012004", "major_topic": true }, { "descriptor": "Reproducibility of Results", "descriptor_ui": "D015203", "major_topic": false }, { "descriptor": "Trust", "descriptor_ui": "D035502", "major_topic": false }, { "descriptor": "Uncertainty", "descriptor_ui": "D035501", "major_topic": false } ], "publication": { "conference_name": null, "date": "2024 Jul 4", "date_precision": "day", "issue": "", "normalized_date": "2024-07-04", "pages": "102929", "proceedings_title": null, "publisher": "", "title": "Artificial intelligence in medicine", "volume": "154", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Can physician judgment enhance model trustworthiness? A case study on predicting pathological lymph nodes in rectal cancer.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Recent advances have made modeling human small intestines in vitro possible, but it remains a challenge to recapitulate fully their structural and functional characteristics. We suspected interstitial flow within the intestine, powered by circulating blood plasma during embryonic organogenesis, to be a vital factor. We aimed to construct an in vivo-like multilayered small intestinal tissue by incorporating interstitial flow into the system and, in turn, developed the micro-small intestine system by differentiating definitive endoderm and mesoderm cells from human pluripotent stem cells simultaneously on a microfluidic device capable of replicating interstitial flow. This approach enhanced cell maturation and led to the development of a three-dimensional small intestine-like tissue with villi-like epithelium and an aligned mesenchymal layer. Our micro-small intestine system not only overcomes the limitations of conventional intestine models but also offers a unique opportunity to gain insights into the detailed mechanisms underlying intestinal tissue development.", "classifications": [ { "id": "Yamamoto", "label": "Group Yamamoto", "parent": "Toyoshima", "type": "group" }, { "id": "Toyoshima", "label": "Team Toyoshima", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Sayaka", "last_name": "Deguchi", "name": null }, { "creator_type": "author", "first_name": "Kaori", "last_name": "Kosugi", "name": null }, { "creator_type": "author", "first_name": "Naoki", "last_name": "Takeishi", "name": null }, { "creator_type": "author", "first_name": "Yukio", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Shiho", "last_name": "Morimoto", "name": null }, { "creator_type": "author", "first_name": "Ryosuke", "last_name": "Negoro", "name": null }, { "creator_type": "author", "first_name": "Fuki", "last_name": "Yokoi", "name": null }, { "creator_type": "author", "first_name": "Hiroki", "last_name": "Futatsusako", "name": null }, { "creator_type": "author", "first_name": "May", "last_name": "Nakajima-Koyama", "name": null }, { "creator_type": "author", "first_name": "Mio", "last_name": "Iwasaki", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Yoshiya", "last_name": "Kawaguchi", "name": null }, { "creator_type": "author", "first_name": "Yu-Suke", "last_name": "Torisawa", "name": null }, { "creator_type": "author", "first_name": "Kazuo", "last_name": "Takayama", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.stem.2024.06.012" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "38996472" } }, "mesh": [ { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Intestine, Small", "descriptor_ui": "D007421", "major_topic": true }, { "descriptor": "Mesoderm", "descriptor_ui": "D008648", "major_topic": false }, { "descriptor": "Pluripotent Stem Cells", "descriptor_ui": "D039904", "major_topic": false }, { "descriptor": "Tissue Engineering", "descriptor_ui": "D023822", "major_topic": true } ], "publication": { "conference_name": null, "date": "2024 Jul 3", "date_precision": "day", "issue": "", "normalized_date": "2024-07-03", "pages": "S1934-5909(24)00220-0", "proceedings_title": null, "publisher": "", "title": "Cell stem cell", "volume": "", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Construction of multilayered small intestine-like tissue by reproducing interstitial flow.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: Cystathionine β-synthase (CBS)-deficient homocystinuria (HCU) is an inherited disorder of sulfur amino acid metabolism with varying severity and organ complications, and a limited knowledge about underlying pathophysiological processes. Here we aimed at getting an in-depth insight into disease mechanisms using a transgenic mouse model of HCU (I278T).\nMETHODS: We assessed metabolic, proteomic and sphingolipidomic changes, and mitochondrial function in tissues and body fluids of I278T mice and WT controls. Furthermore, we evaluated the efficacy of methionine-restricted diet (MRD) in I278T mice.\nRESULTS: In WT mice, we observed a distinct tissue/body fluid compartmentalization of metabolites with up to six-orders of magnitude differences in concentrations among various organs. The I278T mice exhibited the anticipated metabolic imbalance with signs of an increased production of hydrogen sulfide and disturbed persulfidation of free aminothiols. HCU resulted in a significant dysregulation of liver proteome affecting biological oxidations, conjugation of compounds, and metabolism of amino acids, vitamins, cofactors and lipids. Liver sphingolipidomics indicated upregulation of the pro-proliferative sphingosine-1-phosphate signaling pathway. Liver mitochondrial function of HCU mice did not seem to be impaired compared to controls. MRD in I278T mice improved metabolic balance in all tissues and substantially reduced dysregulation of liver proteome.\nCONCLUSION: The study highlights distinct tissue compartmentalization of sulfur-related metabolites in normal mice, extensive metabolome, proteome and sphingolipidome disruptions in I278T mice, and the efficacy of MRD to alleviate some of the HCU-related biochemical abnormalities.", "classifications": [ { "id": "JPMJCR2024", "label": "JPMJCR2024", "researcher": "Motohiro Nishida", "type": "grant" }, { "id": "Akaike", "label": "Group Akaike", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Group Nishida", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Tomas", "last_name": "Majtan", "name": null }, { "creator_type": "author", "first_name": "Thomas", "last_name": "Olsen", "name": null }, { "creator_type": "author", "first_name": "Jitka", "last_name": "Sokolova", "name": null }, { "creator_type": "author", "first_name": "Jakub", "last_name": "Krijt", "name": null }, { "creator_type": "author", "first_name": "Michaela", "last_name": "Křížková", "name": null }, { "creator_type": "author", "first_name": "Tomoaki", "last_name": "Ida", "name": null }, { "creator_type": "author", "first_name": "Tamás", "last_name": "Ditrói", "name": null }, { "creator_type": "author", "first_name": "Hana", "last_name": "Hansikova", "name": null }, { "creator_type": "author", "first_name": "Ondrej", "last_name": "Vit", "name": null }, { "creator_type": "author", "first_name": "Jiri", "last_name": "Petrak", "name": null }, { "creator_type": "author", "first_name": "Ladislav", "last_name": "Kuchař", "name": null }, { "creator_type": "author", "first_name": "Warren D.", "last_name": "Kruger", "name": null }, { "creator_type": "author", "first_name": "Péter", "last_name": "Nagy", "name": null }, { "creator_type": "author", "first_name": "Takaaki", "last_name": "Akaike", "name": null }, { "creator_type": "author", "first_name": "Viktor", "last_name": "Kožich", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.redox.2024.103222" }, "pmcid": { "normalized": "PMC11190558" }, "pmid": { "normalized": "38843767" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cystathionine beta-Synthase", "descriptor_ui": "D003541", "major_topic": true }, { "descriptor": "Disease Models, Animal", "descriptor_ui": "D004195", "major_topic": true }, { "descriptor": "Homocystinuria", "descriptor_ui": "D006712", "major_topic": true }, { "descriptor": "Lipidomics", "descriptor_ui": "D000081362", "major_topic": false }, { "descriptor": "Liver", "descriptor_ui": "D008099", "major_topic": true }, { "descriptor": "Metabolomics", "descriptor_ui": "D055432", "major_topic": true }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Transgenic", "descriptor_ui": "D008822", "major_topic": true }, { "descriptor": "Mitochondria", "descriptor_ui": "D008928", "major_topic": false }, { "descriptor": "Proteome", "descriptor_ui": "D020543", "major_topic": false }, { "descriptor": "Proteomics", "descriptor_ui": "D040901", "major_topic": true }, { "descriptor": "Sphingolipids", "descriptor_ui": "D013107", "major_topic": true } ], "publication": { "conference_name": null, "date": "2024-07", "date_precision": "month", "issue": "", "normalized_date": "2024-07", "pages": "103222", "proceedings_title": null, "publisher": "", "title": "Redox Biology", "volume": "73", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Deciphering pathophysiological mechanisms underlying cystathionine beta-synthase-deficient homocystinuria using targeted metabolomics, liver proteomics, sphingolipidomics and analysis of mitochondrial function", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "We develop a data harmonization approach for C. elegans volumetric microscopy data, still or video, consisting of a standardized format, data pre-processing techniques, and a set of human-in-the-loop machine learning based analysis software tools. We unify a diverse collection of 118 whole-brain neural activity imaging datasets from 5 labs, storing these and accompanying tools in an online repository called WormID (wormid.org). We use this repository to train three existing automated cell identification algorithms to, for the first time, enable accuracy in neural identification that generalizes across labs, approaching human performance in some cases. We mine this repository to identify factors that influence the developmental positioning of neurons. To facilitate communal use of this repository, we created open-source software, code, web-based tools, and tutorials to explore and curate datasets for contribution to the scientific community. This repository provides a growing resource for experimentalists, theorists, and toolmakers to (a) study neuroanatomical organization and neural activity across diverse experimental paradigms, (b) develop and benchmark algorithms for automated neuron detection, segmentation, cell identification, tracking, and activity extraction, and (c) inform models of neurobiological development and function.", "classifications": [ { "id": "Onami", "label": "Group Onami", "parent": "Fujiwara", "type": "group" }, { "id": "Fujiwara", "label": "Team Fujiwara", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Daniel Y.", "last_name": "Sprague", "name": null }, { "creator_type": "author", "first_name": "Kevin", "last_name": "Rusch", "name": null }, { "creator_type": "author", "first_name": "Raymond L.", "last_name": "Dunn", "name": null }, { "creator_type": "author", "first_name": "Jackson M.", "last_name": "Borchardt", "name": null }, { "creator_type": "author", "first_name": "Steven", "last_name": "Ban", "name": null }, { "creator_type": "author", "first_name": "Greg", "last_name": "Bubnis", "name": null }, { "creator_type": "author", "first_name": "Grace C.", "last_name": "Chiu", "name": null }, { "creator_type": "author", "first_name": "Chentao", "last_name": "Wen", "name": null }, { "creator_type": "author", "first_name": "Ryoga", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Shivesh", "last_name": "Chaudhary", "name": null }, { "creator_type": "author", "first_name": "Hyun Jee", "last_name": "Lee", "name": null }, { "creator_type": "author", "first_name": "Zikai", "last_name": "Yu", "name": null }, { "creator_type": "author", "first_name": "Benjamin", "last_name": "Dichter", "name": null }, { "creator_type": "author", "first_name": "Ryan", "last_name": "Ly", "name": null }, { "creator_type": "author", "first_name": "Shuichi", "last_name": "Onami", "name": null }, { "creator_type": "author", "first_name": "Hang", "last_name": "Lu", "name": null }, { "creator_type": "author", "first_name": "Koutarou D.", "last_name": "Kimura", "name": null }, { "creator_type": "author", "first_name": "Eviatar", "last_name": "Yemini", "name": null }, { "creator_type": "author", "first_name": "Saul", "last_name": "Kato", "name": null } ], "identifiers": { "doi": { "normalized": "10.1101/2024.04.28.591397" }, "pmcid": { "normalized": null }, "pmid": { "normalized": null } }, "mesh": [], "publication": { "conference_name": null, "date": "2024 Jun 29", "date_precision": "day", "issue": null, "normalized_date": "2024-06-29", "pages": null, "proceedings_title": null, "publisher": null, "title": null, "volume": null, "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Unifying community-wide whole-brain imaging datasets enables robust automated neuron identification and reveals determinants of neuron positioning in C. elegans.", "url": "", "zotero": { "item_type": "preprint" } }, { "abstract": "Fluorescence imaging is widely used for the mesoscopic mapping of neuronal connectivity. However, neurite reconstruction is challenging, especially when neurons are densely labelled. Here, we report a strategy for the fully automated reconstruction of densely labelled neuronal circuits. Firstly, we establish stochastic super-multicolour labelling with up to seven different fluorescent proteins using the Tetbow method. With this method, each neuron is labelled with a unique combination of fluorescent proteins, which are then imaged and separated by linear unmixing. We also establish an automated neurite reconstruction pipeline based on the quantitative analysis of multiple dyes (QDyeFinder), which identifies neurite fragments with similar colour combinations. To classify colour combinations, we develop unsupervised clustering algorithm, dCrawler, in which data points in multi-dimensional space are clustered based on a given threshold distance. Our strategy allows the reconstruction of neurites for up to hundreds of neurons at the millimetre scale without using their physical continuity.", "classifications": [ { "id": "JPMJCR2021", "label": "JPMJCR2021", "researcher": "Hideki Enomoto", "type": "grant" }, { "id": "Enomoto", "label": "Group Enomoto", "parent": "Enomoto", "type": "group" }, { "id": "Imai", "label": "Group Imai", "parent": "Enomoto", "type": "group" }, { "id": "Enomoto", "label": "Team Enomoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Marcus N.", "last_name": "Leiwe", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Fujimoto", "name": null }, { "creator_type": "author", "first_name": "Toshikazu", "last_name": "Baba", "name": null }, { "creator_type": "author", "first_name": "Daichi", "last_name": "Moriyasu", "name": null }, { "creator_type": "author", "first_name": "Biswanath", "last_name": "Saha", "name": null }, { "creator_type": "author", "first_name": "Richi", "last_name": "Sakaguchi", "name": null }, { "creator_type": "author", "first_name": "Shigenori", "last_name": "Inagaki", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Imai", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41467-024-49455-y" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "38918382" } }, "mesh": [ { "descriptor": "Algorithms", "descriptor_ui": "D000465", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cluster Analysis", "descriptor_ui": "D016000", "major_topic": false }, { "descriptor": "Color", "descriptor_ui": "D003116", "major_topic": true }, { "descriptor": "Image Processing, Computer-Assisted", "descriptor_ui": "D007091", "major_topic": false }, { "descriptor": "Luminescent Proteins", "descriptor_ui": "D008164", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Neurites", "descriptor_ui": "D016501", "major_topic": true }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": true }, { "descriptor": "Optical Imaging", "descriptor_ui": "D061848", "major_topic": false }, { "descriptor": "Staining and Labeling", "descriptor_ui": "D013194", "major_topic": false } ], "publication": { "conference_name": null, "date": "2024 Jun 25", "date_precision": "day", "issue": "1", "normalized_date": "2024-06-25", "pages": "5279", "proceedings_title": null, "publisher": "", "title": "Nature communications", "volume": "15", "year": 2024 }, "ssbd": { "database": [], "repository": [ "ssbd-repos-000346" ] }, "title": "Automated neuronal reconstruction with super-multicolour Tetbow labelling and threshold-based clustering of colour hues.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "We have synthesized 10 analogs of oxylipins, which are nitrogen signaling factors (NSFs) that mediate cell-to-cell communication in the fission yeast Schizosaccharomyces pombe, and evaluated their structure-activity relationships with the aim of developing molecular probes for NSFs. We found that the OH or OAc group at C10 could be replaced with a compact amide (17) or carbamate (19). Introducing an alkyne as a detection tag at C10 led to decreased, though still sufficient, activity. Introducing an alkyne at the C18 position showed a similar trend, suggesting tolerance is relatively low even for compact functional groups such as alkynes. Although introduction of a diazirine moiety as a photoreactive group at the C5 position decreased the activity, we found that introducing diazirine at the C13 position was acceptable, and compound 38 exhibited potent NSF activity. These findings will be helpful in the development of molecular probes for NSFs.", "classifications": [ { "id": "Sodeoka", "label": "Group Sodeoka", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Hiroaki", "last_name": "Matoba", "name": null }, { "creator_type": "author", "first_name": "Kouhei", "last_name": "Oba", "name": null }, { "creator_type": "author", "first_name": "Huanlin", "last_name": "Li", "name": null }, { "creator_type": "author", "first_name": "Yuta", "last_name": "Mizuno", "name": null }, { "creator_type": "author", "first_name": "Qianqian", "last_name": "Wang", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Yoritate", "name": null }, { "creator_type": "author", "first_name": "Mariko", "last_name": "Aso", "name": null }, { "creator_type": "author", "first_name": "Mikiko", "last_name": "Sodeoka", "name": null }, { "creator_type": "author", "first_name": "Minoru", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Yoko", "last_name": "Yashiroda", "name": null }, { "creator_type": "author", "first_name": "Go", "last_name": "Hirai", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.bmcl.2024.129857" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "38909706" } }, "mesh": [ { "descriptor": "Molecular Structure", "descriptor_ui": "D015394", "major_topic": false }, { "descriptor": "Nitrogen", "descriptor_ui": "D009584", "major_topic": false }, { "descriptor": "Oxylipins", "descriptor_ui": "D054883", "major_topic": false }, { "descriptor": "Schizosaccharomyces", "descriptor_ui": "D012568", "major_topic": true }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Structure-Activity Relationship", "descriptor_ui": "D013329", "major_topic": false } ], "publication": { "conference_name": null, "date": "2024 Jun 21", "date_precision": "day", "issue": "", "normalized_date": "2024-06-21", "pages": "129857", "proceedings_title": null, "publisher": "", "title": "Bioorganic & medicinal chemistry letters", "volume": "", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Structure-activity relationship study of nitrogen signaling factors.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Motivations for pornography use may vary across gender identities, sexual orientations, and geographical regions, warranting examination to promote individual and public health. The aims of this study were to validate the Pornography Use Motivations Scale (PUMS) in a diverse, multicultural sample, and develop a short form (PUMS-8) that can assess a wide range of pornography use motivations. Using data from 42 countries (N = 75,117; M(age) = 32.07; SD(age) = 12.37), enabled us to thoroughly evaluate the dimensionality, validity, and reliability of the Pornography Use Motivations Scale (PUMS), leading to the development of the more concise PUMS-8 short scale. Additionally, language-, nationality-, gender-, and sexual-orientation-based measurement invariance tests were conducted to test the comparability across groups. Both the PUMS and the PUMS-8 assess eight pornography use motivations, and both demonstrated excellent psychometric properties. Sexual Pleasure emerged as the most frequent motivation for pornography use across countries, genders, and sexual orientations, while differences were observed concerning other motivations (e.g. self-exploration was more prevalent among gender-diverse individuals than men or women). The motivational background of pornography use showed high similarity in the examined countries. Both the PUMS and the PUMS-8 are reliable and valid measurement tools to assess different types of motivations for pornography use across countries, genders, and sexual orientations. Both scales are recommended for use in research and clinical settings.", "classifications": [ { "id": "Fujiwara", "label": "Group Fujiwara", "parent": "Fujiwara", "type": "group" }, { "id": "Fujiwara", "label": "Team Fujiwara", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Monika", "last_name": "Koos", "name": null }, { "creator_type": "author", "first_name": "Lena", "last_name": "Nagy", "name": null }, { "creator_type": "author", "first_name": "Shane W.", "last_name": "Kraus", "name": null }, { "creator_type": "author", "first_name": "Zsolt", "last_name": "Demetrovics", "name": null }, { "creator_type": "author", "first_name": "Marc N.", "last_name": "Potenza", "name": null }, { "creator_type": "author", "first_name": "Emilie", "last_name": "Gaudet", "name": null }, { "creator_type": "author", "first_name": "Rafael", "last_name": "Ballester-Arnal", "name": null }, { "creator_type": "author", "first_name": "Dominik", "last_name": "Batthyany", "name": null }, { "creator_type": "author", "first_name": "Sophie", "last_name": "Bergeron", "name": null }, { "creator_type": "author", "first_name": "Joel", "last_name": "Billieux", "name": null }, { "creator_type": "author", "first_name": "Peer", "last_name": "Briken", "name": null }, { "creator_type": "author", "first_name": "Julius", "last_name": "Burkauskas", "name": null }, { "creator_type": "author", "first_name": "Georgina", "last_name": "Cardenas-Lopez", "name": null }, { "creator_type": "author", "first_name": "Joana", "last_name": "Carvalho", "name": null }, { "creator_type": "author", "first_name": "Jesus", "last_name": "Castro-Calvo", "name": null }, { "creator_type": "author", "first_name": "Yun-Hsuan", "last_name": "Chang", "name": null }, { "creator_type": "author", "first_name": "Lijun", "last_name": "Chen", "name": null }, { "creator_type": "author", "first_name": "Giacomo", "last_name": "Ciocca", "name": null }, { "creator_type": "author", "first_name": "Ornella", "last_name": "Corazza", "name": null }, { "creator_type": "author", "first_name": "Rita I.", "last_name": "Csako", "name": null }, { "creator_type": "author", "first_name": "David P.", "last_name": "Fernandez", "name": null }, { "creator_type": "author", "first_name": "Hironobu", "last_name": "Fujiwara", "name": null }, { "creator_type": "author", "first_name": "Elaine F.", "last_name": "Fernandez", "name": null }, { "creator_type": "author", "first_name": "Johannes", "last_name": "Fuss", "name": null }, { "creator_type": "author", "first_name": "Roman", "last_name": "Gabrhelik", "name": null }, { "creator_type": "author", "first_name": "Ateret", "last_name": "Gewirtz-Meydan", "name": null }, { "creator_type": "author", "first_name": "Biljana", "last_name": "Gjoneska", "name": null }, { "creator_type": "author", "first_name": "Mateusz", "last_name": "Gola", "name": null }, { "creator_type": "author", "first_name": "Joshua B.", "last_name": "Grubbs", "name": null }, { "creator_type": "author", "first_name": "Hashim T.", "last_name": "Hashim", "name": null }, { "creator_type": "author", "first_name": "Yi-Ping", "last_name": "Hsieh", "name": null }, { "creator_type": "author", "first_name": "Md Saiful", "last_name": "Islam", "name": null }, { "creator_type": "author", "first_name": "Mustafa", "last_name": "Ismail", "name": null }, { "creator_type": "author", "first_name": "Martha C.", "last_name": "Jimenez-Martinez", "name": null }, { "creator_type": "author", "first_name": "Tanja", "last_name": "Jurin", "name": null }, { "creator_type": "author", "first_name": "Ondrej", "last_name": "Kalina", "name": null }, { "creator_type": "author", "first_name": "Verena", "last_name": "Klein", "name": null }, { "creator_type": "author", "first_name": "Andras", "last_name": "Kolto", "name": null }, { "creator_type": "author", "first_name": "Sang-Kyu", "last_name": "Lee", "name": null }, { "creator_type": "author", "first_name": "Karol", "last_name": "Lewczuk", "name": null }, { "creator_type": "author", "first_name": "Christine", "last_name": "Lochner", "name": null }, { "creator_type": "author", "first_name": "Silvia", "last_name": "Lopez-Alvarado", "name": null }, { "creator_type": "author", "first_name": "Katerina", "last_name": "Lukavska", "name": null }, { "creator_type": "author", "first_name": "Percy", "last_name": "Mayta-Tristan", "name": null }, { "creator_type": "author", "first_name": "Dan J.", "last_name": "Miller", "name": null }, { "creator_type": "author", "first_name": "Olga", "last_name": "Orosova", "name": null }, { "creator_type": "author", "first_name": "Gabor", "last_name": "Orosz", "name": null }, { "creator_type": "author", "first_name": "Fernando P.", "last_name": "Ponce", "name": null }, { "creator_type": "author", "first_name": "Gonzalo R.", "last_name": "Quintana", "name": null }, { "creator_type": "author", "first_name": "Gabriel C.", "last_name": "Quintero Garzola", "name": null }, { "creator_type": "author", "first_name": "Jano", "last_name": "Ramos-Diaz", "name": null }, { "creator_type": "author", "first_name": "Kevin", "last_name": "Rigaud", "name": null }, { "creator_type": "author", "first_name": "Ann", "last_name": "Rousseau", "name": null }, { "creator_type": "author", "first_name": "Marco De Tubino", "last_name": "Scanavino", "name": null }, { "creator_type": "author", "first_name": "Marion K.", "last_name": "Schulmeyer", "name": null }, { "creator_type": "author", "first_name": "Pratap", "last_name": "Sharan", "name": null }, { "creator_type": "author", "first_name": "Mami", "last_name": "Shibata", "name": null }, { "creator_type": "author", "first_name": "Sheikh", "last_name": "Shoib", "name": null }, { "creator_type": "author", "first_name": "Vera", "last_name": "Sigre-Leiros", "name": null }, { "creator_type": "author", "first_name": "Luke", "last_name": "Sniewski", "name": null }, { "creator_type": "author", "first_name": "Ognen", "last_name": "Spasovski", "name": null }, { "creator_type": "author", "first_name": "Vesta", "last_name": "Steibliene", "name": null }, { "creator_type": "author", "first_name": "Dan J.", "last_name": "Stein", "name": null }, { "creator_type": "author", "first_name": "Julian", "last_name": "Strizek", "name": null }, { "creator_type": "author", "first_name": "Alexandar", "last_name": "Stulhofer", "name": null }, { "creator_type": "author", "first_name": "Berk C.", "last_name": "Unsal", "name": null }, { "creator_type": "author", "first_name": "Marie-Pier", "last_name": "Vaillancourt-Morel", "name": null }, { "creator_type": "author", "first_name": "Marie Claire", "last_name": "Van Hout", "name": null }, { "creator_type": "author", "first_name": "Beata", "last_name": "Bothe", "name": null } ], "identifiers": { "doi": { "normalized": "10.1080/00224499.2024.2359641" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "38905162" } }, "mesh": [ { "descriptor": "Adolescent", "descriptor_ui": "D000293", "major_topic": false }, { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Cross-Cultural Comparison", "descriptor_ui": "D003431", "major_topic": false }, { "descriptor": "Erotica", "descriptor_ui": "D004882", "major_topic": true }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Motivation", "descriptor_ui": "D009042", "major_topic": true }, { "descriptor": "Psychometrics", "descriptor_ui": "D011594", "major_topic": true }, { "descriptor": "Reproducibility of Results", "descriptor_ui": "D015203", "major_topic": false }, { "descriptor": "Sexual Behavior", "descriptor_ui": "D012725", "major_topic": true }, { "descriptor": "Surveys and Questionnaires", "descriptor_ui": "D011795", "major_topic": false }, { "descriptor": "Young Adult", "descriptor_ui": "D055815", "major_topic": false } ], "publication": { "conference_name": null, "date": "2024 Jun 21", "date_precision": "day", "issue": "", "normalized_date": "2024-06-21", "pages": "1-16", "proceedings_title": null, "publisher": "", "title": "Journal of sex research", "volume": "", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Why Do People Watch Pornography? Cross-Cultural Validation of the Pornography Use Motivations Scale (PUMS) and Its Short Form (PUMS-8).", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Insulin plays a crucial role in regulating the metabolism of blood glucose, amino acids (aa), and lipids in humans. However, the mechanisms by which insulin selectively regulates these metabolites are not fully understood. To address this question, we used mathematical modeling to identify the selective regulatory mechanisms of insulin on blood aa and lipids. Our study revealed that insulin negatively regulates the influx and positively regulates the efflux of lipids, consistent with previous findings. By contrast, we did not observe the previously reported insulin’s negative regulation of branched-chain aa (BCAA) influx; instead, we found that insulin positively regulates BCAA efflux. We observed that the earlier peak time of lipids compared to BCAA is dependent on insulin’s negative regulation of their influx. Overall, our findings shed new light on how insulin selectively regulates the levels of different metabolites in human blood, providing insights into the metabolic disorder pathogenesis and potential therapies.", "classifications": [ { "id": "JPMJCR2123", "label": "JPMJCR2123", "researcher": "Shinya Kuroda", "type": "grant" }, { "id": "Kuroda", "label": "Group Kuroda", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Suguru", "last_name": "Fujita", "name": null }, { "creator_type": "author", "first_name": "Ken-ichi", "last_name": "Hironaka", "name": null }, { "creator_type": "author", "first_name": "Yasuaki", "last_name": "Karasawa", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Kuroda", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.isci.2024.109833" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "39055606" } }, "mesh": [], "publication": { "conference_name": null, "date": "2024 Jun 21", "date_precision": "day", "issue": "6", "normalized_date": "2024-06-21", "pages": "", "proceedings_title": null, "publisher": "", "title": "iScience", "volume": "27", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Model selection reveals selective regulation of blood amino acid and lipid metabolism by insulin in humans.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Strategic design for the construction of contiguous tetrasubstituted carbons represents a daunting challenge in synthetic organic chemistry. Herein, we report a combined experimental and computational investigation aimed at developing catalytic aerobic carbooxygenation, involving the intramolecular addition of tertiary radicals to geminally di-substituted-alkenes followed by aerobic oxygenation. This reaction provides a straightforward route to various alpha,alpha,beta,beta-tetrasubstituted gamma-lactones, which can be readily transformed into hexasubstituted gamma-lactones through allylation/translactonization. Computational analysis reveals that the key mechanistic foundation for achieving the developed aerobic carbooxygenation involves the design of endothermic (energetically uphill) C-C bond formation followed by exothermic (energetically downhill) oxygenation. Furthermore, we highlight a unique fluorine- induced stereoelectronic effect that stabilizes the endothermic stereo-determining transition state.", "classifications": [ { "id": "Sodeoka", "label": "Group Sodeoka", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Florian", "last_name": "Punner", "name": null }, { "creator_type": "author", "first_name": "Yoshihiro", "last_name": "Sohtome", "name": null }, { "creator_type": "author", "first_name": "Yanzong", "last_name": "Lyu", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Hashizume", "name": null }, { "creator_type": "author", "first_name": "Mai", "last_name": "Akakabe", "name": null }, { "creator_type": "author", "first_name": "Mami", "last_name": "Yoshimura", "name": null }, { "creator_type": "author", "first_name": "Yoko", "last_name": "Yashiroda", "name": null }, { "creator_type": "author", "first_name": "Minoru", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Mikiko", "last_name": "Sodeoka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/anie.202405876" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "39031750" } }, "mesh": [], "publication": { "conference_name": null, "date": "2024 Jun 20", "date_precision": "day", "issue": "", "normalized_date": "2024-06-20", "pages": "e202405876", "proceedings_title": null, "publisher": "", "title": "Angewandte Chemie (International ed. in English)", "volume": "", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Catalytic Aerobic Carbooxygenation for the Construction of Vicinal Tetrasubstituted Centers: Application to the Synthesis of Hexasubstituted gamma-Lactones.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Spermatogonial stem cells (SSCs) undergo self-renewal division to sustain spermatogenesis. Although it is possible to derive SSC cultures in most mouse strains, SSCs from a 129 background never proliferate under the same culture conditions, suggesting they have distinct self-renewal requirements. Here, we established long-term culture conditions for SSCs from mice of the 129 background (129 mice). An analysis of 129 testes showed significant reduction of GDNF and CXCL12, whereas FGF2, INHBA and INHBB were higher than in testes of C57BL/6 mice. An analysis of undifferentiated spermatogonia in 129 mice showed higher expression of Chrna4, which encodes an acetylcholine (Ach) receptor component. By supplementing medium with INHBA and Ach, SSC cultures were derived from 129 mice. Following lentivirus transduction for marking donor cells, transplanted cells re-initiated spermatogenesis in infertile mouse testes and produced transgenic offspring. These results suggest that the requirements of SSC self-renewal in mice are diverse, which has important implications for understanding self-renewal mechanisms in various animal species.", "classifications": [ { "id": "Yamamoto", "label": "Group Yamamoto", "parent": "Toyoshima", "type": "group" }, { "id": "Toyoshima", "label": "Team Toyoshima", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Mito", "last_name": "Kanatsu-Shinohara", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Hiroko", "last_name": "Morimoto", "name": null }, { "creator_type": "author", "first_name": "Tianjiao", "last_name": "Liu", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Shinohara", "name": null } ], "identifiers": { "doi": { "normalized": "10.1242/dev.202553" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "38934417" } }, "mesh": [ { "descriptor": "Adult Germline Stem Cells", "descriptor_ui": "D000072956", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Cell Proliferation", "descriptor_ui": "D049109", "major_topic": false }, { "descriptor": "Cell Self Renewal", "descriptor_ui": "D000066673", "major_topic": false }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": true }, { "descriptor": "Mice, Inbred Strains", "descriptor_ui": "D008815", "major_topic": false }, { "descriptor": "Mice, Transgenic", "descriptor_ui": "D008822", "major_topic": false }, { "descriptor": "Receptors, Nicotinic", "descriptor_ui": "D011978", "major_topic": false }, { "descriptor": "Spermatogenesis", "descriptor_ui": "D013091", "major_topic": true }, { "descriptor": "Spermatogonia", "descriptor_ui": "D013093", "major_topic": true }, { "descriptor": "Stem Cells", "descriptor_ui": "D013234", "major_topic": false }, { "descriptor": "Testis", "descriptor_ui": "D013737", "major_topic": true } ], "publication": { "conference_name": null, "date": "2024 Jun 15", "date_precision": "day", "issue": "12", "normalized_date": "2024-06-15", "pages": "dev202553", "proceedings_title": null, "publisher": "", "title": "Development (Cambridge, England)", "volume": "151", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Spermatogonial stem cells in the 129 inbred strain exhibit unique requirements for self-renewal.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Leigh syndrome is the most common inherited mitochondrial disease in children and is often fatal within the first few years of life. In 2020, mutations in the gene encoding sulfide:quinone oxidoreductase (SQOR), a mitochondrial protein, were identified as a cause of Leigh syndrome. Here, we report that mice with a mutation in the gene encoding SQOR (SqorDeltaN/DeltaN mice), which prevented SQOR from entering mitochondria, had clinical and pathological manifestations of Leigh syndrome. SqorDeltaN/DeltaN mice had increased blood lactate levels that were associated with markedly decreased complex IV activity and increased hydrogens sulfide (H2S) levels. Because H2S is produced by both gut microbiota and host tissue, we tested whether metronidazole (a broad-spectrum antibiotic) or a sulfur-restricted diet rescues SqorDeltaN/DeltaN mice from developing Leigh syndrome. Daily treatment with metronidazole alleviated increased H2S levels, normalized complex IV activity and blood lactate levels, and prolonged the survival of SqorDeltaN/DeltaN mice. Similarly, a sulfur-restricted diet normalized blood lactate levels and inhibited the development of Leigh syndrome. Taken together, these observations suggest that mitochondrial SQOR is essential to prevent systemic accumulation of H2S. Administration of metronidazole or a sulfur-restricted diet may be therapeutic approaches to treatment of patients with Leigh syndrome caused by mutations in SQOR.", "classifications": [ { "id": "JPMJCR2024", "label": "JPMJCR2024", "researcher": "Motohiro Nishida", "type": "grant" }, { "id": "Akaike", "label": "Group Akaike", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Group Nishida", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Eiki", "last_name": "Kanemaru", "name": null }, { "creator_type": "author", "first_name": "Kakeru", "last_name": "Shimoda", "name": null }, { "creator_type": "author", "first_name": "Eizo", "last_name": "Marutani", "name": null }, { "creator_type": "author", "first_name": "Masanobu", "last_name": "Morita", "name": null }, { "creator_type": "author", "first_name": "Maria", "last_name": "Miranda", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Miyazaki", "name": null }, { "creator_type": "author", "first_name": "Claire", "last_name": "Sinow", "name": null }, { "creator_type": "author", "first_name": "Rohit", "last_name": "Sharma", "name": null }, { "creator_type": "author", "first_name": "Fangcong", "last_name": "Dong", "name": null }, { "creator_type": "author", "first_name": "Donald B.", "last_name": "Bloch", "name": null }, { "creator_type": "author", "first_name": "Takaaki", "last_name": "Akaike", "name": null }, { "creator_type": "author", "first_name": "Fumito", "last_name": "Ichinose", "name": null } ], "identifiers": { "doi": { "normalized": "10.1172/jci170994" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "38870029" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Hydrogen Sulfide", "descriptor_ui": "D006862", "major_topic": true }, { "descriptor": "Leigh Disease", "descriptor_ui": "D007888", "major_topic": true }, { "descriptor": "Metronidazole", "descriptor_ui": "D008795", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mitochondria", "descriptor_ui": "D008928", "major_topic": true }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": false }, { "descriptor": "Quinone Reductases", "descriptor_ui": "D011808", "major_topic": true }, { "descriptor": "Sulfides", "descriptor_ui": "D013440", "major_topic": false } ], "publication": { "conference_name": null, "date": "2024 Jun 13", "date_precision": "day", "issue": "", "normalized_date": "2024-06-13", "pages": "e170994", "proceedings_title": null, "publisher": "", "title": "The Journal of clinical investigation", "volume": "", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Exclusion of sulfide:quinone oxidoreductase from mitochondria causes Leigh-like disease in mice by impairing sulfide metabolism.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Ferroptosis is a form of regulated cell death induced by iron-dependent accumulation of lipid hydroperoxides. Selenoprotein glutathione peroxidase 4 (GPX4) suppresses ferroptosis by detoxifying lipid hydroperoxides via a catalytic selenocysteine (Sec) residue. Sec, the genetically encoded 21(st) amino acid, is biosynthesized from a reactive selenium donor on its cognate tRNA([Ser]Sec). It is thought that intracellular selenium must be delivered 'safely' and 'efficiently' by a carrier protein owing to its high reactivity and very low concentrations. Here, we identified peroxiredoxin 6 (PRDX6) as a novel selenoprotein synthesis factor. Loss of PRDX6 decreases the expression of selenoproteins and induces ferroptosis via a reduction in GPX4. Mechanistically, PRDX6 increases the efficiency of intracellular selenium utilization by transferring selenium between proteins within the selenocysteyl-tRNA([Ser]Sec) synthesis machinery, leading to efficient synthesis of selenocysteyl-tRNA([Ser]Sec). These findings highlight previously unidentified selenium metabolic systems and provide new insights into ferroptosis.", "classifications": [ { "id": "JPMJCR2024", "label": "JPMJCR2024", "researcher": "Motohiro Nishida", "type": "grant" }, { "id": "Akaike", "label": "Group Akaike", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Group Nishida", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Hiroaki", "last_name": "Fujita", "name": null }, { "creator_type": "author", "first_name": "Yu-Ki", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Seiryo", "last_name": "Ogata", "name": null }, { "creator_type": "author", "first_name": "Noriyuki", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Sota", "last_name": "Kuno", "name": null }, { "creator_type": "author", "first_name": "Uladzimir", "last_name": "Barayeu", "name": null }, { "creator_type": "author", "first_name": "Takaaki", "last_name": "Akaike", "name": null }, { "creator_type": "author", "first_name": "Yasumitsu", "last_name": "Ogra", "name": null }, { "creator_type": "author", "first_name": "Kazuhiro", "last_name": "Iwai", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41594-024-01329-z" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "38867112" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Ferroptosis", "descriptor_ui": "D000079403", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Iron", "descriptor_ui": "D007501", "major_topic": true }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Peroxiredoxin VI", "descriptor_ui": "D054465", "major_topic": true }, { "descriptor": "Phospholipid Hydroperoxide Glutathione Peroxidase", "descriptor_ui": "D000080662", "major_topic": true }, { "descriptor": "RNA, Transfer, Amino Acyl", "descriptor_ui": "D012346", "major_topic": false }, { "descriptor": "Selenium", "descriptor_ui": "D012643", "major_topic": true }, { "descriptor": "Selenocysteine", "descriptor_ui": "D017279", "major_topic": false }, { "descriptor": "Selenoproteins", "descriptor_ui": "D051140", "major_topic": false } ], "publication": { "conference_name": null, "date": "2024 Jun 12", "date_precision": "day", "issue": "", "normalized_date": "2024-06-12", "pages": "", "proceedings_title": null, "publisher": "", "title": "Nature structural & molecular biology", "volume": "", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "PRDX6 augments selenium utilization to limit iron toxicity and ferroptosis.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "KSP-1007 is a novel bicyclic boronate-based broad-spectrum β-lactamase inhibitor and is being developed in combination with meropenem (MEM) for the treatment of infections caused by carbapenem-resistant Gram-negative bacteria, a global health concern, and here, we describe its characteristics. KSP-1007 exhibited low apparent inhibition constant (K(i) (app)) values against all classes of β-lactamase, including imipenemase types and oxacillinase types from Acinetobacter baumannii. Against 207 Enterobacterales and 55 A. baumannii, including carbapenemase producers, KSP-1007 at fixed concentrations of 4, 8, and 16 µg/mL dose-dependently potentiated the in vitro activity of MEM in broth microdilution MIC testing. The MIC(90) of MEM/KSP-1007 at 8 µg/mL against Enterobacterales was lower than those of MEM/vaborbactam, ceftazidime/avibactam, imipenem/relebactam, and colistin and similar to those of aztreonam/avibactam, cefiderocol, and tigecycline. The in vitro activity of MEM/KSP-1007 at ≥4 µg/mL against Enterobacterales harboring metallo-β-lactamase was superior to that of cefepime/taniborbactam. MEM/KSP-1007 showed excellent activity against Escherichia coli with PBP3 mutations and New Delhi metallo-β-lactamase compared to aztreonam/avibactam, cefepime/taniborbactam, and cefiderocol. MEM/KSP-1007 at 8 µg/mL showed greater efficacy against A. baumannii than these comparators except for cefiderocol, tigecycline, and colistin. A 2-fold reduction in MEM MIC against 96 Pseudomonas aeruginosa was observed in combination with KSP-1007. MEM/KSP-1007 demonstrated bactericidal activity against carbapenemase-producing Enterobacterales, A. baumannii, and P. aeruginosa based on minimum bactericidal concentration/MIC ratios of ≤4. KSP-1007 enhanced the in vivo activity of MEM against carbapenemase-producing Enterobacterales, A. baumannii, and P. aeruginosa in murine systemic, complicated urinary tract, and thigh infection models. Collectively, MEM/KSP-1007 has a good profile for treating carbapenem-resistant Gram-negative bacterial infections.", "classifications": [ { "id": "Fujimoto", "label": "Group Fujimoto", "parent": "Ueda", "type": "group" }, { "id": "Ueda", "label": "Team Ueda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Koji", "last_name": "Takemoto", "name": null }, { "creator_type": "author", "first_name": "Ryo", "last_name": "Nakayama", "name": null }, { "creator_type": "author", "first_name": "Koichi", "last_name": "Fujimoto", "name": null }, { "creator_type": "author", "first_name": "Yumiko", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Yukiko", "last_name": "Takarabe", "name": null }, { "creator_type": "author", "first_name": "Masako", "last_name": "Honsho", "name": null }, { "creator_type": "author", "first_name": "Sachiko", "last_name": "Kitahara", "name": null }, { "creator_type": "author", "first_name": "Yoshihiko", "last_name": "Noguchi", "name": null }, { "creator_type": "author", "first_name": "Hidehito", "last_name": "Matsui", "name": null }, { "creator_type": "author", "first_name": "Tomoyasu", "last_name": "Hirose", "name": null }, { "creator_type": "author", "first_name": "Yukihiro", "last_name": "Asami", "name": null }, { "creator_type": "author", "first_name": "Jun", "last_name": "Hidaka", "name": null }, { "creator_type": "author", "first_name": "Toshiaki", "last_name": "Sunazuka", "name": null }, { "creator_type": "author", "first_name": "Hideaki", "last_name": "Hanaki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1128/aac.01602-23" }, "pmcid": { "normalized": "PMC11620503" }, "pmid": { "normalized": "38709005" } }, "mesh": [ { "descriptor": "Acinetobacter baumannii", "descriptor_ui": "D040981", "major_topic": true }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Anti-Bacterial Agents", "descriptor_ui": "D000900", "major_topic": true }, { "descriptor": "Azabicyclo Compounds", "descriptor_ui": "D053961", "major_topic": true }, { "descriptor": "Bacterial Proteins", "descriptor_ui": "D001426", "major_topic": false }, { "descriptor": "beta-Lactamase Inhibitors", "descriptor_ui": "D065093", "major_topic": true }, { "descriptor": "beta-Lactamases", "descriptor_ui": "D001618", "major_topic": true }, { "descriptor": "Boronic Acids", "descriptor_ui": "D001897", "major_topic": false }, { "descriptor": "Carbapenem-Resistant Enterobacteriaceae", "descriptor_ui": "D000073182", "major_topic": false }, { "descriptor": "Carbapenems", "descriptor_ui": "D015780", "major_topic": false }, { "descriptor": "Ceftazidime", "descriptor_ui": "D002442", "major_topic": false }, { "descriptor": "Cephalosporins", "descriptor_ui": "D002511", "major_topic": false }, { "descriptor": "Colistin", "descriptor_ui": "D003091", "major_topic": false }, { "descriptor": "Drug Combinations", "descriptor_ui": "D004338", "major_topic": false }, { "descriptor": "Gram-Negative Bacteria", "descriptor_ui": "D006090", "major_topic": false }, { "descriptor": "Meropenem", "descriptor_ui": "D000077731", "major_topic": true }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Microbial Sensitivity Tests", "descriptor_ui": "D008826", "major_topic": true }, { "descriptor": "Pseudomonas aeruginosa", "descriptor_ui": "D011550", "major_topic": false } ], "publication": { "conference_name": null, "date": "2024 Jun 5", "date_precision": "day", "issue": "6", "normalized_date": "2024-06-05", "pages": "e0160223", "proceedings_title": null, "publisher": "", "title": "Antimicrobial agents and chemotherapy", "volume": "68", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "In vitro and in vivo activities of KSP-1007, a broad-spectrum inhibitor of serine- and metallo-β-lactamases, in combination with meropenem against carbapenem-resistant Gram-negative bacteria.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The incidence of vulvar carcinoma varies by race; however, it is a rare disease, and its genomic profiles remain largely unknown. This study examined the characteristics of vulvar squamous cell carcinoma (VSCC) in Japanese patients, focusing on genomic profiles and potential racial disparities. The study included two Japanese groups: the National Cancer Center Hospital (NCCH) group comprised 19 patients diagnosed between 2015 and 2023, and the Center for Cancer Genomics and Advanced Therapeutics group comprised 29 patients diagnosed between 2019 and 2022. Somatic mutations were identified by targeted or panel sequencing, and TP53 was identified as the most common mutation (52-81%), followed by HRAS (7-26%), CDKN2A (21-24%), and PIK3CA (5-10%). The mutation frequencies, except for TP53, were similar to those of Caucasian cohorts. In the NCCH group, 16 patients of HPV-independent tumors were identified by immunohistochemistry and genotyping. Univariate analysis revealed that TP53-mutated patients were associated with a poor prognosis (log-rank test, P = 0.089). Japanese VSCC mutations resembled those of Caucasian vulvar carcinomas, and TP53 mutations predicted prognosis regardless of ethnicity. The present findings suggest potential molecular-targeted therapies for select VSCC patients.", "classifications": [ { "id": "Hamamoto", "label": "Group Hamamoto", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Erisa", "last_name": "Fujii", "name": null }, { "creator_type": "author", "first_name": "Mayumi Kobayashi", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Maiko", "last_name": "Yamaguchi", "name": null }, { "creator_type": "author", "first_name": "Daiki", "last_name": "Higuchi", "name": null }, { "creator_type": "author", "first_name": "Takafumi", "last_name": "Koyama", "name": null }, { "creator_type": "author", "first_name": "Masaaki", "last_name": "Komatsu", "name": null }, { "creator_type": "author", "first_name": "Ryuji", "last_name": "Hamamoto", "name": null }, { "creator_type": "author", "first_name": "Mitsuya", "last_name": "Ishikawa", "name": null }, { "creator_type": "author", "first_name": "Tomoyasu", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Kohno", "name": null }, { "creator_type": "author", "first_name": "Kouya", "last_name": "Shiraishi", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Yoshida", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41598-024-63913-z" }, "pmcid": { "normalized": "PMC11156893" }, "pmid": { "normalized": "38844774" } }, "mesh": [ { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Aged, 80 and over", "descriptor_ui": "D000369", "major_topic": false }, { "descriptor": "Carcinoma, Squamous Cell", "descriptor_ui": "D002294", "major_topic": true }, { "descriptor": "Class I Phosphatidylinositol 3-Kinases", "descriptor_ui": "D058534", "major_topic": false }, { "descriptor": "Cyclin-Dependent Kinase Inhibitor p16", "descriptor_ui": "D019941", "major_topic": false }, { "descriptor": "East Asian People", "descriptor_ui": "D000095225", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Genomics", "descriptor_ui": "D023281", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Japan", "descriptor_ui": "D007564", "major_topic": false }, { "descriptor": "Japanese people", "descriptor_ui": "C000724324", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": true }, { "descriptor": "Prognosis", "descriptor_ui": "D011379", "major_topic": false }, { "descriptor": "Proto-Oncogene Proteins p21(ras)", "descriptor_ui": "D016283", "major_topic": false }, { "descriptor": "Tumor Suppressor Protein p53", "descriptor_ui": "D016159", "major_topic": true }, { "descriptor": "Vulvar Neoplasms", "descriptor_ui": "D014846", "major_topic": true } ], "publication": { "conference_name": null, "date": "2024-06", "date_precision": "month", "issue": "1", "normalized_date": "2024-06", "pages": "13058", "proceedings_title": null, "publisher": "", "title": "Scientific Reports", "volume": "14", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Genomic profiles of Japanese patients with vulvar squamous cell carcinoma", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: In an extensive genomic analysis of lung adenocarcinomas (LUADs), driver mutations have been recognized as potential targets for molecular therapy. However, there remain cases where target genes are not identified. Super-enhancers and structural variants are frequently identified in several hundred loci per case. Despite this, most cancer research has approached the analysis of these data sets separately, without merging and comparing the data, and there are no examples of integrated analysis in LUAD.\nMETHODS: We performed an integrated analysis of super-enhancers and structural variants in a cohort of 174 LUAD cases that lacked clinically actionable genetic alterations. To achieve this, we conducted both WGS and H3K27Ac ChIP-seq analyses using samples with driver gene mutations and those without, allowing for a comprehensive investigation of the potential roles of super-enhancer in LUAD cases.\nRESULTS: We demonstrate that most genes situated in these overlapped regions were associated with known and previously unknown driver genes and aberrant expression resulting from the formation of super-enhancers accompanied by genomic structural abnormalities. Hi-C and long-read sequencing data further corroborated this insight. When we employed CRISPR-Cas9 to induce structural abnormalities that mimicked cases with outlier ERBB2 gene expression, we observed an elevation in ERBB2 expression. These abnormalities are associated with a higher risk of recurrence after surgery, irrespective of the presence or absence of driver mutations.\nCONCLUSIONS: Our findings suggest that aberrant gene expression linked to structural polymorphisms can significantly impact personalized cancer treatment by facilitating the identification of driver mutations and prognostic factors, contributing to a more comprehensive understanding of LUAD pathogenesis.", "classifications": [ { "id": "Hamamoto", "label": "Group Hamamoto", "parent": "Okamoto", "type": "group" }, { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Syuzo", "last_name": "Kaneko", "name": null }, { "creator_type": "author", "first_name": "Ken", "last_name": "Takasawa", "name": null }, { "creator_type": "author", "first_name": "Ken", "last_name": "Asada", "name": null }, { "creator_type": "author", "first_name": "Kouya", "last_name": "Shiraishi", "name": null }, { "creator_type": "author", "first_name": "Noriko", "last_name": "Ikawa", "name": null }, { "creator_type": "author", "first_name": "Hidenori", "last_name": "Machino", "name": null }, { "creator_type": "author", "first_name": "Norio", "last_name": "Shinkai", "name": null }, { "creator_type": "author", "first_name": "Maiko", "last_name": "Matsuda", "name": null }, { "creator_type": "author", "first_name": "Mari", "last_name": "Masuda", "name": null }, { "creator_type": "author", "first_name": "Shungo", "last_name": "Adachi", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Kazuma", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Nobuji", "last_name": "Kouno", "name": null }, { "creator_type": "author", "first_name": "Amina", "last_name": "Bolatkan", "name": null }, { "creator_type": "author", "first_name": "Masaaki", "last_name": "Komatsu", "name": null }, { "creator_type": "author", "first_name": "Masayoshi", "last_name": "Yamada", "name": null }, { "creator_type": "author", "first_name": "Mototaka", "last_name": "Miyake", "name": null }, { "creator_type": "author", "first_name": "Hirokazu", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Akiko", "last_name": "Tateishi", "name": null }, { "creator_type": "author", "first_name": "Takaaki", "last_name": "Mizuno", "name": null }, { "creator_type": "author", "first_name": "Yu", "last_name": "Okubo", "name": null }, { "creator_type": "author", "first_name": "Masami", "last_name": "Mukai", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Yukihiro", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Hidehito", "last_name": "Horinouchi", "name": null }, { "creator_type": "author", "first_name": "Shun-Ichi", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Yuichiro", "last_name": "Ohe", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null }, { "creator_type": "author", "first_name": "Vassiliki", "last_name": "Saloura", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Kohno", "name": null }, { "creator_type": "author", "first_name": "Ryuji", "last_name": "Hamamoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1186/s12943-024-02035-6" }, "pmcid": { "normalized": "PMC11165761" }, "pmid": { "normalized": "38862995" } }, "mesh": [ { "descriptor": "Adenocarcinoma of Lung", "descriptor_ui": "D000077192", "major_topic": true }, { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Biomarkers, Tumor", "descriptor_ui": "D014408", "major_topic": false }, { "descriptor": "Enhancer Elements, Genetic", "descriptor_ui": "D004742", "major_topic": true }, { "descriptor": "Erb-b2 Receptor Tyrosine Kinases", "descriptor_ui": "D018719", "major_topic": true }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Gene Expression Regulation, Neoplastic", "descriptor_ui": "D015972", "major_topic": true }, { "descriptor": "Genomic Structural Variation", "descriptor_ui": "D056914", "major_topic": false }, { "descriptor": "Genomics", "descriptor_ui": "D023281", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Lung Neoplasms", "descriptor_ui": "D008175", "major_topic": true }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": false }, { "descriptor": "Prognosis", "descriptor_ui": "D011379", "major_topic": false } ], "publication": { "conference_name": null, "date": "2024-06", "date_precision": "month", "issue": "1", "normalized_date": "2024-06", "pages": "126", "proceedings_title": null, "publisher": "", "title": "Molecular Cancer", "volume": "23", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Mechanism of ERBB2 gene overexpression by the formation of super-enhancer with genomic structural abnormalities in lung adenocarcinoma without clinically actionable genetic alterations", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Oxygen is critical for all metazoan organisms on the earth and impacts various biological processes in physiological and pathological conditions. While oxygen-sensing systems inducing acute hypoxic responses, including the hypoxia-inducible factor pathway, have been identified, those operating in prolonged hypoxia remain to be elucidated. Here we show that pyridoxine 5'-phosphate oxidase (PNPO), which catalyses bioactivation of vitamin B6, serves as an oxygen sensor and regulates lysosomal activity in macrophages. Decreased PNPO activity under prolonged hypoxia reduced an active form of vitamin B6, pyridoxal 5'-phosphate (PLP), and inhibited lysosomal acidification, which in macrophages led to iron dysregulation, TET2 protein loss and delayed resolution of the inflammatory response. Among PLP-dependent metabolism, supersulfide synthesis was suppressed in prolonged hypoxia, resulting in the lysosomal inhibition and consequent proinflammatory phenotypes of macrophages. The PNPO-PLP axis creates a distinct layer of oxygen sensing that gradually shuts down PLP-dependent metabolism in response to prolonged oxygen deprivation.", "classifications": [ { "id": "Akaike", "label": "Group Akaike", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Hiroki", "last_name": "Sekine", "name": null }, { "creator_type": "author", "first_name": "Haruna", "last_name": "Takeda", "name": null }, { "creator_type": "author", "first_name": "Norihiko", "last_name": "Takeda", "name": null }, { "creator_type": "author", "first_name": "Akihiro", "last_name": "Kishino", "name": null }, { "creator_type": "author", "first_name": "Hayato", "last_name": "Anzawa", "name": null }, { "creator_type": "author", "first_name": "Takayuki", "last_name": "Isagawa", "name": null }, { "creator_type": "author", "first_name": "Nao", "last_name": "Ohta", "name": null }, { "creator_type": "author", "first_name": "Shohei", "last_name": "Murakami", "name": null }, { "creator_type": "author", "first_name": "Hideya", "last_name": "Iwaki", "name": null }, { "creator_type": "author", "first_name": "Nobufumi", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Shu", "last_name": "Kimura", "name": null }, { "creator_type": "author", "first_name": "Zun", "last_name": "Liu", "name": null }, { "creator_type": "author", "first_name": "Koichiro", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Fumiki", "last_name": "Katsuoka", "name": null }, { "creator_type": "author", "first_name": "Masayuki", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Fumihito", "last_name": "Miura", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Masatomo", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Yoshihiro", "last_name": "Izumi", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Fujita", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Yamagata", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Bamba", "name": null }, { "creator_type": "author", "first_name": "Takaaki", "last_name": "Akaike", "name": null }, { "creator_type": "author", "first_name": "Norio", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Kengo", "last_name": "Kinoshita", "name": null }, { "creator_type": "author", "first_name": "Hozumi", "last_name": "Motohashi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s42255-024-01053-4" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "38822028" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Hypoxia", "descriptor_ui": "D015687", "major_topic": false }, { "descriptor": "Hypoxia", "descriptor_ui": "D000860", "major_topic": false }, { "descriptor": "Inflammation", "descriptor_ui": "D007249", "major_topic": false }, { "descriptor": "Lysosomes", "descriptor_ui": "D008247", "major_topic": true }, { "descriptor": "Macrophages", "descriptor_ui": "D008264", "major_topic": true }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Oxygen", "descriptor_ui": "D010100", "major_topic": false }, { "descriptor": "Pyridoxal Phosphate", "descriptor_ui": "D011732", "major_topic": true }, { "descriptor": "Vitamin B 6", "descriptor_ui": "D025101", "major_topic": false } ], "publication": { "conference_name": null, "date": "2024 May 31", "date_precision": "day", "issue": "", "normalized_date": "2024-05-31", "pages": "", "proceedings_title": null, "publisher": "", "title": "Nature metabolism", "volume": "", "year": 2024 }, "ssbd": { "database": [], "repository": [ "ssbd-repos-000446" ] }, "title": "PNPO-PLP axis senses prolonged hypoxia in macrophages by regulating lysosomal activity.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "It has been reported that accumulation of senescent cells in various tissues contributes to pathological aging and that elimination of senescent cells (senolysis) improves age-associated pathologies. Here, we demonstrate that inhibition of sodium-glucose co-transporter 2 (SGLT2) enhances clearance of senescent cells, thereby ameliorating age-associated phenotypic changes. In a mouse model of dietary obesity, short-term treatment with the SGLT2 inhibitor canagliflozin reduced the senescence load in visceral adipose tissue and improved adipose tissue inflammation and metabolic dysfunction, but normalization of plasma glucose by insulin treatment had no effect on senescent cells. Canagliflozin extended the lifespan of mice with premature aging even when treatment was started in middle age. Metabolomic analyses revealed that short-term treatment with canagliflozin upregulated 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside, enhancing immune-mediated clearance of senescent cells by downregulating expression of programmed cell death-ligand 1. These findings suggest that inhibition of SGLT2 has an indirect senolytic effect by enhancing endogenous immunosurveillance of senescent cells.", "classifications": [ { "id": "JPMJCR2123", "label": "JPMJCR2123", "researcher": "Shinya Kuroda", "type": "grant" }, { "id": "Kuroda", "label": "Group Kuroda", "parent": "Kuroda", "type": "group" }, { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Goro", "last_name": "Katsuumi", "name": null }, { "creator_type": "author", "first_name": "Ippei", "last_name": "Shimizu", "name": null }, { "creator_type": "author", "first_name": "Masayoshi", "last_name": "Suda", "name": null }, { "creator_type": "author", "first_name": "Yohko", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Takaaki", "last_name": "Furihata", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Joki", "name": null }, { "creator_type": "author", "first_name": "Chieh-Lun", "last_name": "Hsiao", "name": null }, { "creator_type": "author", "first_name": "Liang", "last_name": "Jiaqi", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Fujiki", "name": null }, { "creator_type": "author", "first_name": "Manabu", "last_name": "Abe", "name": null }, { "creator_type": "author", "first_name": "Masataka", "last_name": "Sugimoto", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Tohru", "last_name": "Minamino", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s43587-024-00642-y" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "38816549" } }, "mesh": [ { "descriptor": "Aging", "descriptor_ui": "D000375", "major_topic": true }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Canagliflozin", "descriptor_ui": "D000068896", "major_topic": true }, { "descriptor": "Cellular Senescence", "descriptor_ui": "D016922", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Obesity", "descriptor_ui": "D009765", "major_topic": false }, { "descriptor": "Sodium-Glucose Transporter 2", "descriptor_ui": "D051297", "major_topic": true }, { "descriptor": "Sodium-Glucose Transporter 2 Inhibitors", "descriptor_ui": "D000077203", "major_topic": true } ], "publication": { "conference_name": null, "date": "2024 May 30", "date_precision": "day", "issue": "", "normalized_date": "2024-05-30", "pages": "", "proceedings_title": null, "publisher": "", "title": "Nature aging", "volume": "", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "SGLT2 inhibition eliminates senescent cells and alleviates pathological aging.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: Both small-cell carcinoma (SCLC) and large-cell neuroendocrine carcinoma (LCNEC) of the lung are often clinically dealt with as being in the same category as neuroendocrine carcinoma, and their clinical differences have not been adequately assessed. METHODS: The postoperative prognosis was retrospectively analyzed using the data of 196 patients who underwent resection for SCLC or LCNEC. RESULTS: Of the patients included, 99 (50.5%) had SCLC and 97 (49.5%) had LCNEC. The median duration of follow-up was 39 months (interquartile range [IQR] 21-76) and 56 months (IQR 21-87) for SCLC and LCNEC, respectively. The estimated 5-year overall survival (OS) probabilities were 53.7% and 62.7% (p = 0.133) for patients with SCLC and LCNEC, respectively. In the SCLC group, a multivariate analysis showed that adjuvant chemotherapy (hazard ratio 0.54, 95% confidence interval 0.30-0.99, p = 0.04) was the only factor that was significantly associated with OS. In the LCNEC group, univariate analyses demonstrated that pathologic stage I (p = 0.01) was the only factor that was associated with better OS after surgery. CONCLUSIONS: We found different clinical features in SCLC and LCNEC; in patients with SCLC, because OS could be expected to significantly improve with postoperative adjuvant chemotherapy, patients with resected SCLC of any pathologic stage should receive adjuvant chemotherapy. For patients with LCNEC, because pathologic stage I LCNEC is related to better prognosis than any other stages, a thorough clinical staging, including invasive staging, according to present guidelines should be performed to identify clinical stage I LCNEC with the highest certainty.", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Wakako", "last_name": "Fujiwara", "name": null }, { "creator_type": "author", "first_name": "Masaya", "last_name": "Yotsukura", "name": null }, { "creator_type": "author", "first_name": "Yukihiro", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Kazuo", "last_name": "Nakagawa", "name": null }, { "creator_type": "author", "first_name": "Jumpei", "last_name": "Kashima", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null }, { "creator_type": "author", "first_name": "Shun-Ichi", "last_name": "Watanabe", "name": null } ], "identifiers": { "doi": { "normalized": "10.1245/s10434-024-15505-4" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "38811497" } }, "mesh": [ { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Carcinoma, Large Cell", "descriptor_ui": "D018287", "major_topic": true }, { "descriptor": "Carcinoma, Neuroendocrine", "descriptor_ui": "D018278", "major_topic": true }, { "descriptor": "Chemotherapy, Adjuvant", "descriptor_ui": "D017024", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Follow-Up Studies", "descriptor_ui": "D005500", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Lung Neoplasms", "descriptor_ui": "D008175", "major_topic": true }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Neoplasm Staging", "descriptor_ui": "D009367", "major_topic": false }, { "descriptor": "Prognosis", "descriptor_ui": "D011379", "major_topic": false }, { "descriptor": "Retrospective Studies", "descriptor_ui": "D012189", "major_topic": false }, { "descriptor": "Small Cell Lung Carcinoma", "descriptor_ui": "D055752", "major_topic": true }, { "descriptor": "Survival Rate", "descriptor_ui": "D015996", "major_topic": false } ], "publication": { "conference_name": null, "date": "2024 May 29", "date_precision": "day", "issue": "", "normalized_date": "2024-05-29", "pages": "", "proceedings_title": null, "publisher": "", "title": "Annals of surgical oncology", "volume": "", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Clinical and Pathologic Differences between Small-Cell Carcinoma and Large-Cell Neuroendocrine Carcinoma of the Lung.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Although the mRNA SARS-CoV-2 vaccine has improved the mortality rate in the general population, its efficacy against rapidly mutating virus strains, especially in kidney transplant recipients, remains unclear. We examined the anti-SARS-CoV-2 spike protein IgG antibody and neutralizing antibody titers and cellular immunity against B.1.1, BA.1, and BA.5 antigens in 73 uninfected kidney recipients and 16 uninfected healthy controls who received three doses of an mRNA SARS-CoV-2 vaccine. The IgG antibody titers were significantly lower in recipients than in healthy controls. Similarly, neutralizing antibody titers against three viral variants were significantly lower in recipients. When the virus was mutated, the neutralizing antibody titers decreased significantly in both groups. In cellular immunity analysis, the number of spike-specific CD8 + non-naïve T cells against three variants significantly decreased in recipients. Conversely, the frequency of spike-specific Th2 CD4 + T-cells in recipients was higher than that in healthy controls. Nineteen recipients and six healthy controls also received a bivalent omicron-containing booster vaccine, leading to increase IgG and neutralizing antibody titers in both groups. After that, eleven recipients and five healthy controls received XBB.1.5 monovalent vaccines, increasing the neutralizing antibody titers against not only XBB.1.5, but also EG.5.1 and BA.2.86 antigens in kidney recipients. Although kidney recipients did not gain sufficient immunity against Omicron BA.5 with the third dose of vaccine, humoral response against mutant SARS-CoV-2 lineages significantly increased after bivalent Omicron-containing booster vaccine and the XBB.1.5 monovalent vaccine. Therefore, it is important for kidney recipients to continue to administer updated vaccines.", "classifications": [ { "id": "Yamamoto", "label": "Group Yamamoto", "parent": "Toyoshima", "type": "group" }, { "id": "Toyoshima", "label": "Team Toyoshima", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Keita", "last_name": "Kawashiro", "name": null }, { "creator_type": "author", "first_name": "Rigel", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Takuto", "last_name": "Nogimori", "name": null }, { "creator_type": "author", "first_name": "Shuhei", "last_name": "Tsujino", "name": null }, { "creator_type": "author", "first_name": "Naoya", "last_name": "Iwahara", "name": null }, { "creator_type": "author", "first_name": "Takayuki", "last_name": "Hirose", "name": null }, { "creator_type": "author", "first_name": "Kazufumi", "last_name": "Okada", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Takasuke", "last_name": "Fukuhara", "name": null }, { "creator_type": "author", "first_name": "Kiyohiko", "last_name": "Hotta", "name": null }, { "creator_type": "author", "first_name": "Nobuo", "last_name": "Shinohara", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41598-024-63147-z" }, "pmcid": { "normalized": "PMC11133393" }, "pmid": { "normalized": "38806644" } }, "mesh": [ { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Antibodies, Neutralizing", "descriptor_ui": "D057134", "major_topic": true }, { "descriptor": "Antibodies, Viral", "descriptor_ui": "D000914", "major_topic": true }, { "descriptor": "COVID-19", "descriptor_ui": "D000086382", "major_topic": true }, { "descriptor": "COVID-19 Vaccines", "descriptor_ui": "D000086663", "major_topic": true }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Immunity, Cellular", "descriptor_ui": "D007111", "major_topic": false }, { "descriptor": "Immunization, Secondary", "descriptor_ui": "D007117", "major_topic": false }, { "descriptor": "Immunoglobulin G", "descriptor_ui": "D007074", "major_topic": true }, { "descriptor": "Kidney Transplantation", "descriptor_ui": "D016030", "major_topic": true }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "SARS-CoV-2", "descriptor_ui": "D000086402", "major_topic": true }, { "descriptor": "Spike Glycoprotein, Coronavirus", "descriptor_ui": "D064370", "major_topic": true }, { "descriptor": "Transplant Recipients", "descriptor_ui": "D066027", "major_topic": false }, { "descriptor": "Vaccination", "descriptor_ui": "D014611", "major_topic": false } ], "publication": { "conference_name": null, "date": "2024 May 28", "date_precision": "day", "issue": "1", "normalized_date": "2024-05-28", "pages": "12176", "proceedings_title": null, "publisher": "", "title": "Scientific reports", "volume": "14", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Neutralizing antibody responses and cellular responses against SARS-CoV-2 Omicron subvariants after mRNA SARS-CoV-2 vaccination in kidney transplant recipients.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: One significant challenge in addressing the coronavirus disease 2019 (COVID-19) pandemic is to grasp a comprehensive picture of its infectious mechanisms. We urgently need a consistent framework to capture the intricacies of its complicated viral infectious processes and diverse symptoms. RESULTS: We systematized COVID-19 infectious processes through an ontological approach and provided a unified description framework of causal relationships from the early infectious stage to severe clinical manifestations based on the homeostasis imbalance process ontology (HoIP). HoIP covers a broad range of processes in the body, ranging from normal to abnormal. Moreover, our imbalance model enabled us to distinguish viral functional demands from immune defense processes, thereby supporting the development of new drugs, and our research demonstrates how ontological reasoning contributes to the identification of patients at severe risk. CONCLUSIONS: The HoIP organises knowledge of COVID-19 infectious processes and related entities, such as molecules, drugs, and symptoms, with a consistent descriptive framework. HoIP is expected to harmonise the description of various heterogeneous processes and improve the interoperability of COVID-19 knowledge through the COVID-19 ontology harmonisation working group.", "classifications": [ { "id": "Onami", "label": "Group Onami", "parent": "Fujiwara", "type": "group" }, { "id": "Fujiwara", "label": "Team Fujiwara", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yuki", "last_name": "Yamagata", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Kushida", "name": null }, { "creator_type": "author", "first_name": "Shuichi", "last_name": "Onami", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Masuya", "name": null } ], "identifiers": { "doi": { "normalized": "10.1186/s12911-024-02516-0" }, "pmcid": { "normalized": "PMC11110177" }, "pmid": { "normalized": "38778394" } }, "mesh": [ { "descriptor": "Biological Ontologies", "descriptor_ui": "D064229", "major_topic": true }, { "descriptor": "COVID-19", "descriptor_ui": "D000086382", "major_topic": true }, { "descriptor": "Homeostasis", "descriptor_ui": "D006706", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "SARS-CoV-2", "descriptor_ui": "D000086402", "major_topic": false } ], "publication": { "conference_name": null, "date": "2024 May 22", "date_precision": "day", "issue": "Suppl 4", "normalized_date": "2024-05-22", "pages": "301", "proceedings_title": null, "publisher": "", "title": "BMC medical informatics and decision making", "volume": "23", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Homeostasis imbalance process ontology: a study on COVID-19 infectious processes.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Epigenetic reprogramming resets parental epigenetic memories and differentiates primordial germ cells (PGCs) into mitotic pro-spermatogonia or oogonia. This process ensures sexually dimorphic germ cell development for totipotency(1). In vitro reconstitution of epigenetic reprogramming in humans remains a fundamental challenge. Here we establish a strategy for inducing epigenetic reprogramming and differentiation of pluripotent stem-cell-derived human PGC-like cells (hPGCLCs) into mitotic pro-spermatogonia or oogonia, coupled with their extensive amplification (about >10(10)-fold). Bone morphogenetic protein (BMP) signalling is a key driver of these processes. BMP-driven hPGCLC differentiation involves attenuation of the MAPK (ERK) pathway and both de novo and maintenance DNA methyltransferase activities, which probably promote replication-coupled, passive DNA demethylation. hPGCLCs deficient in TET1, an active DNA demethylase abundant in human germ cells(2,3), differentiate into extraembryonic cells, including amnion, with de-repression of key genes that bear bivalent promoters. These cells fail to fully activate genes vital for spermatogenesis and oogenesis, and their promoters remain methylated. Our study provides a framework for epigenetic reprogramming in humans and an important advance in human biology. Through the generation of abundant mitotic pro-spermatogonia and oogonia-like cells, our results also represent a milestone for human in vitro gametogenesis research and its potential translation into reproductive medicine.", "classifications": [ { "id": "Yamamoto", "label": "Group Yamamoto", "parent": "Toyoshima", "type": "group" }, { "id": "Toyoshima", "label": "Team Toyoshima", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yusuke", "last_name": "Murase", "name": null }, { "creator_type": "author", "first_name": "Ryuta", "last_name": "Yokogawa", "name": null }, { "creator_type": "author", "first_name": "Yukihiro", "last_name": "Yabuta", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Nagano", "name": null }, { "creator_type": "author", "first_name": "Yoshitaka", "last_name": "Katou", "name": null }, { "creator_type": "author", "first_name": "Manami", "last_name": "Mizuyama", "name": null }, { "creator_type": "author", "first_name": "Ayaka", "last_name": "Kitamura", "name": null }, { "creator_type": "author", "first_name": "Pimpitcha", "last_name": "Puangsricharoen", "name": null }, { "creator_type": "author", "first_name": "Chika", "last_name": "Yamashiro", "name": null }, { "creator_type": "author", "first_name": "Bo", "last_name": "Hu", "name": null }, { "creator_type": "author", "first_name": "Ken", "last_name": "Mizuta", "name": null }, { "creator_type": "author", "first_name": "Taro", "last_name": "Tsujimura", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Kosuke", "last_name": "Ogata", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Ishihama", "name": null }, { "creator_type": "author", "first_name": "Mitinori", "last_name": "Saitou", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41586-024-07526-6" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "38768632" } }, "mesh": [ { "descriptor": "Amnion", "descriptor_ui": "D000650", "major_topic": false }, { "descriptor": "Bone Morphogenetic Proteins", "descriptor_ui": "D019485", "major_topic": false }, { "descriptor": "Cellular Reprogramming", "descriptor_ui": "D065150", "major_topic": true }, { "descriptor": "DNA Methylation", "descriptor_ui": "D019175", "major_topic": false }, { "descriptor": "Epigenesis, Genetic", "descriptor_ui": "D044127", "major_topic": true }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Gene Expression Regulation, Developmental", "descriptor_ui": "D018507", "major_topic": false }, { "descriptor": "Germ Cells", "descriptor_ui": "D005854", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "In Vitro Techniques", "descriptor_ui": "D066298", "major_topic": true }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "MAP Kinase Signaling System", "descriptor_ui": "D020935", "major_topic": false }, { "descriptor": "Mitosis", "descriptor_ui": "D008938", "major_topic": false }, { "descriptor": "Mixed Function Oxygenases", "descriptor_ui": "D006899", "major_topic": false }, { "descriptor": "Oogenesis", "descriptor_ui": "D009866", "major_topic": false }, { "descriptor": "Oogonia", "descriptor_ui": "D009867", "major_topic": false }, { "descriptor": "Pluripotent Stem Cells", "descriptor_ui": "D039904", "major_topic": false }, { "descriptor": "Promoter Regions, Genetic", "descriptor_ui": "D011401", "major_topic": false }, { "descriptor": "Proto-Oncogene Proteins", "descriptor_ui": "D011518", "major_topic": false }, { "descriptor": "Spermatogenesis", "descriptor_ui": "D013091", "major_topic": false }, { "descriptor": "Spermatogonia", "descriptor_ui": "D013093", "major_topic": false } ], "publication": { "conference_name": null, "date": "2024 May 20", "date_precision": "day", "issue": "", "normalized_date": "2024-05-20", "pages": "", "proceedings_title": null, "publisher": "", "title": "Nature", "volume": "", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "In vitro reconstitution of epigenetic reprogramming in the human germ line.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Accumulating evidence suggests that endothelial cells can be useful therapeutic targets. One of the potential targets is an endothelial cell-specific protein, Roundabout4 (ROBO4). ROBO4 has been shown to ameliorate multiple diseases in mice, including infectious diseases and sepsis. However, its mechanisms are not fully understood. In this study, using RNA-seq analysis, we found that ROBO4 downregulates prostaglandin-endoperoxide synthase 2 (PTGS2), which encodes cyclooxygenase-2. Mechanistic analysis reveals that ROBO4 interacts with IQ motif-containing GTPase-activating protein 1 (IQGAP1) and TNF receptor-associated factor 7 (TRAF7), a ubiquitin E3 ligase. In this complex, ROBO4 enhances IQGAP1 ubiquitination through TRAF7, inhibits prolonged RAC1 activation, and decreases PTGS2 expression in inflammatory endothelial cells. In addition, Robo4-deficiency in mice exacerbates PTGS2-associated inflammatory diseases, including arthritis, edema, and pain. Thus, we reveal the molecular mechanism by which ROBO4 suppresses the inflammatory response and vascular hyperpermeability, highlighting its potential as a promising therapeutic target for inflammatory diseases.", "classifications": [ { "id": "Yamamoto", "label": "Group Yamamoto", "parent": "Toyoshima", "type": "group" }, { "id": "Toyoshima", "label": "Team Toyoshima", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Masato", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Keisuke", "last_name": "Shirakura", "name": null }, { "creator_type": "author", "first_name": "Yui", "last_name": "Takayama", "name": null }, { "creator_type": "author", "first_name": "Miki", "last_name": "Muatsui", "name": null }, { "creator_type": "author", "first_name": "Yukio", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Junya", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Shota", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Nobumasa", "last_name": "Hino", "name": null }, { "creator_type": "author", "first_name": "Takefumi", "last_name": "Doi", "name": null }, { "creator_type": "author", "first_name": "Masanori", "last_name": "Obana", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Fujio", "name": null }, { "creator_type": "author", "first_name": "Kazuo", "last_name": "Takayama", "name": null }, { "creator_type": "author", "first_name": "Yoshiaki", "last_name": "Okada", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s42003-024-06317-z" }, "pmcid": { "normalized": "PMC11102558" }, "pmid": { "normalized": "38762541" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cyclooxygenase 2", "descriptor_ui": "D051546", "major_topic": true }, { "descriptor": "Endothelial Cells", "descriptor_ui": "D042783", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Inflammation", "descriptor_ui": "D007249", "major_topic": true }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Receptors, Cell Surface", "descriptor_ui": "D011956", "major_topic": true }, { "descriptor": "Roundabout Proteins", "descriptor_ui": "D000097905", "major_topic": false } ], "publication": { "conference_name": null, "date": "2024 May 18", "date_precision": "day", "issue": "1", "normalized_date": "2024-05-18", "pages": "599", "proceedings_title": null, "publisher": "", "title": "Communications biology", "volume": "7", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Endothelial ROBO4 suppresses PTGS2/COX-2 expression and inflammatory diseases.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Lipid droplet (LD) accumulation in hepatocytes is one of the major symptoms associated with fatty liver disease. Mitochondria play a key role in catabolizing fatty acids for energy production through beta-oxidation. The interplay between mitochondria and LD assumes a crucial role in lipid metabolism, while it is obscure how mitochondrial morphology affects systemic lipid metabolism in the liver. We previously reported that cilnidipine, an already existing anti-hypertensive drug, can prevent pathological mitochondrial fission by inhibiting protein-protein interaction between dynamin-related protein 1 (Drp1) and filamin, an actin-binding protein. Here, we found that cilnidipine and its new dihydropyridine (DHP) derivative, 1,4-DHP, which lacks Ca(2+) channel-blocking action of cilnidipine, prevent the palmitic acid-induced Drp1-filamin interaction, LD accumulation and cytotoxicity of human hepatic HepG2 cells. Cilnidipine and 1,4-DHP also suppressed the LD accumulation accompanied by reducing mitochondrial contact with LD in obese model and high-fat diet-fed mouse livers. These results propose that targeting the Drp1-filamin interaction become a new strategy for the prevention or treatment of fatty liver disease.", "classifications": [ { "id": "JPMJCR2024", "label": "JPMJCR2024", "researcher": "Motohiro Nishida", "type": "grant" }, { "id": "Nishida", "label": "Group Nishida", "parent": "Nishida", "type": "group" }, { "id": "Nishimura", "label": "Group Nishimura", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Kohei", "last_name": "Ariyoshi", "name": null }, { "creator_type": "author", "first_name": "Kazuhiro", "last_name": "Nishiyama", "name": null }, { "creator_type": "author", "first_name": "Yuri", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Xinya", "last_name": "Mi", "name": null }, { "creator_type": "author", "first_name": "Tomoya", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Yasu-Taka", "last_name": "Azuma", "name": null }, { "creator_type": "author", "first_name": "Akiyuki", "last_name": "Nishimura", "name": null }, { "creator_type": "author", "first_name": "Motohiro", "last_name": "Nishida", "name": null } ], "identifiers": { "doi": { "normalized": "10.3390/ijms25105446" }, "pmcid": { "normalized": "PMC11122359" }, "pmid": { "normalized": "38791484" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Diet, High-Fat", "descriptor_ui": "D059305", "major_topic": false }, { "descriptor": "Dihydropyridines", "descriptor_ui": "D004095", "major_topic": true }, { "descriptor": "Dynamins", "descriptor_ui": "D034281", "major_topic": true }, { "descriptor": "Hep G2 Cells", "descriptor_ui": "D056945", "major_topic": false }, { "descriptor": "Hepatocytes", "descriptor_ui": "D022781", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Lipid Droplets", "descriptor_ui": "D066292", "major_topic": true }, { "descriptor": "Lipid Metabolism", "descriptor_ui": "D050356", "major_topic": false }, { "descriptor": "Liver", "descriptor_ui": "D008099", "major_topic": true }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mitochondria", "descriptor_ui": "D008928", "major_topic": false }, { "descriptor": "Mitochondrial Dynamics", "descriptor_ui": "D063154", "major_topic": false } ], "publication": { "conference_name": null, "date": "2024 May 17", "date_precision": "day", "issue": "10", "normalized_date": "2024-05-17", "pages": "", "proceedings_title": null, "publisher": "", "title": "International journal of molecular sciences", "volume": "25", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Inhibition of Drp1-Filamin Protein Complex Prevents Hepatic Lipid Droplet Accumulation by Increasing Mitochondria-Lipid Droplet Contact.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Although cellular senescence is a key factor in organismal aging, with both positive and negative effects on individuals, its mechanisms remain largely unknown. Thus, integrating knowledge is essential to explain how cellular senescence manifests in tissue damage and age-related diseases. Here, we propose an ontological model that organizes knowledge of cellular senescence in a computer-readable form. We manually annotated and defined cellular senescence processes, molecules, anatomical structures, phenotypes, and other entities based on the Homeostasis Imbalance Process ontology (HOIP). We described the mechanisms as causal relationships of processes and modelled a homeostatic imbalance between stress and stress response in cellular senescence for a unified framework. HOIP was assessed formally, and the relationships between cellular senescence and diseases were inferred for higher-order knowledge processing. We visualized cellular senescence processes to support knowledge utilization. Our study provides a knowledge base to help elucidate mechanisms linking cellular and organismal aging.", "classifications": [ { "id": "Onami", "label": "Group Onami", "parent": "Fujiwara", "type": "group" }, { "id": "Fujiwara", "label": "Team Fujiwara", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yuki", "last_name": "Yamagata", "name": null }, { "creator_type": "author", "first_name": "Tsubasa", "last_name": "Fukuyama", "name": null }, { "creator_type": "author", "first_name": "Shuichi", "last_name": "Onami", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Masuya", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41597-024-03331-y" }, "pmcid": { "normalized": "PMC11087592" }, "pmid": { "normalized": "38729991" } }, "mesh": [ { "descriptor": "Aging", "descriptor_ui": "D000375", "major_topic": false }, { "descriptor": "Cellular Senescence", "descriptor_ui": "D016922", "major_topic": true }, { "descriptor": "Homeostasis", "descriptor_ui": "D006706", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false } ], "publication": { "conference_name": null, "date": "2024 May 10", "date_precision": "day", "issue": "1", "normalized_date": "2024-05-10", "pages": "485", "proceedings_title": null, "publisher": "", "title": "Scientific data", "volume": "11", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Prototyping an Ontological Framework for Cellular Senescence Mechanisms: A Homeostasis Imbalance Perspective.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Cell deformability is an essential determinant for tissue-scale mechanical nature, such as fluidity and rigidity, and is thus crucial for tissue homeostasis and stable developmental processes. However, large-scale simulations of deformable cells have been restricted to those of polygonal-shaped cells, limiting our understanding of populations of arbitrarily deformable cells, such as mesenchymal, amoeboid cells, and nonconfluent epithelial cells. Here, we present an efficient approach for simulating large populations of nonpolygonally deformable cells with considerably higher computational efficiency than existing methods. Using the method, we demonstrate that the densely packed active cell population interacting via excluded volume interactions exhibits a fluid-to-fluid transition. An experimentally measurable index of topological defects, defined using the number of neighboring cells, is also proposed to characterize this transition. This study provides a flexible approach to tissue-scale cell population and a broader perspective on the biological fluid phases.", "classifications": [ { "id": "JPMJCR1923", "label": "JPMJCR1923", "researcher": "Satoshi Sawai", "type": "grant" }, { "id": "Ishihara", "label": "Group Ishihara", "parent": "Sawai", "type": "group" }, { "id": "Sawai", "label": "Group Sawai", "parent": "Sawai", "type": "group" }, { "id": "Sawai", "label": "Team Sawai", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Nen", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Shuji", "last_name": "Ishihara", "name": null } ], "identifiers": { "doi": { "normalized": "10.1126/sciadv.adi8433" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "38718115" } }, "mesh": [ { "descriptor": "Cell Shape", "descriptor_ui": "D048430", "major_topic": false }, { "descriptor": "Computer Simulation", "descriptor_ui": "D003198", "major_topic": false }, { "descriptor": "Epithelial Cells", "descriptor_ui": "D004847", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Models, Biological", "descriptor_ui": "D008954", "major_topic": true }, { "descriptor": "Phase Transition", "descriptor_ui": "D044367", "major_topic": false } ], "publication": { "conference_name": null, "date": "2024 May 10", "date_precision": "day", "issue": "19", "normalized_date": "2024-05-10", "pages": "eadi8433", "proceedings_title": null, "publisher": "", "title": "Science advances", "volume": "10", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Cell deformability drives fluid-to-fluid phase transition in active cell monolayers.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The molecular system regulating cellular mechanical properties remains unexplored at single-cell resolution mainly due to a limited ability to combine mechanophenotyping with unbiased transcriptional screening. Here, we describe an electroporation-based lipid-bilayer assay for cell surface tension and transcriptomics (ELASTomics), a method in which oligonucleotide-labelled macromolecules are imported into cells via nanopore electroporation to assess the mechanical state of the cell surface and are enumerated by sequencing. ELASTomics can be readily integrated with existing single-cell sequencing approaches and enables the joint study of cell surface mechanics and underlying transcriptional regulation at an unprecedented resolution. We validate ELASTomics via analysis of cancer cell lines from various malignancies and show that the method can accurately identify cell types and assess cell surface tension. ELASTomics enables exploration of the relationships between cell surface tension, surface proteins, and transcripts along cell lineages differentiating from the haematopoietic progenitor cells of mice. We study the surface mechanics of cellular senescence and demonstrate that RRAD regulates cell surface tension in senescent TIG-1 cells. ELASTomics provides a unique opportunity to profile the mechanical and molecular phenotypes of single cells and can dissect the interplay among these in a range of biological contexts.", "classifications": [ { "id": "JPMJCR2124", "label": "JPMJCR2124", "researcher": "Hirofumi Shintaku", "type": "grant" }, { "id": "Nishikii", "label": "Group Nishikii", "parent": "Shintaku", "type": "group" }, { "id": "Shintaku", "label": "Group Shintaku", "parent": "Shintaku", "type": "group" }, { "id": "Shintaku", "label": "Team Shintaku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Akifumi", "last_name": "Shiomi", "name": null }, { "creator_type": "author", "first_name": "Taikopaul", "last_name": "Kaneko", "name": null }, { "creator_type": "author", "first_name": "Kaori", "last_name": "Nishikawa", "name": null }, { "creator_type": "author", "first_name": "Arata", "last_name": "Tsuchida", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Isoshima", "name": null }, { "creator_type": "author", "first_name": "Mayuko", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Kiminori", "last_name": "Toyooka", "name": null }, { "creator_type": "author", "first_name": "Kentaro", "last_name": "Doi", "name": null }, { "creator_type": "author", "first_name": "Hidekazu", "last_name": "Nishikii", "name": null }, { "creator_type": "author", "first_name": "Hirofumi", "last_name": "Shintaku", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41467-024-48088-5" }, "pmcid": { "normalized": "PMC11101642" }, "pmid": { "normalized": "38760380" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Cell Membrane", "descriptor_ui": "D002462", "major_topic": false }, { "descriptor": "Cellular Senescence", "descriptor_ui": "D016922", "major_topic": false }, { "descriptor": "Electroporation", "descriptor_ui": "D018274", "major_topic": false }, { "descriptor": "Gene Expression Profiling", "descriptor_ui": "D020869", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Phenotype", "descriptor_ui": "D010641", "major_topic": false }, { "descriptor": "Single-Cell Analysis", "descriptor_ui": "D059010", "major_topic": true }, { "descriptor": "Surface Tension", "descriptor_ui": "D013500", "major_topic": false }, { "descriptor": "Transcriptome", "descriptor_ui": "D059467", "major_topic": true } ], "publication": { "conference_name": null, "date": "2024-05", "date_precision": "month", "issue": "1", "normalized_date": "2024-05", "pages": "3812", "proceedings_title": null, "publisher": "", "title": "Nature Communications", "volume": "15", "year": 2024 }, "ssbd": { "database": [], "repository": [ "ssbd-repos-000343" ] }, "title": "High-throughput mechanical phenotyping and transcriptomics of single cells", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Hydrogels containing chondrocytes have exhibited excellent potential in regenerating hyaline cartilage. However, chondrocytes are vulnerable to dedifferentiation during in vitro culture, leading to fibrosis and mechanical degradation of newly formed cartilage. We propose to modulate cartilage formation via the developed chondrocyte pericellular matrix (PCM) -like scaffolds for the first time, in which the S, M and L-sized scaffolds were fabricated by femtosecond laser maskless optical projection lithography of bovine serum albumin-glyceryl methacrylate hydrogel. Chondrocytes on the M PCM-like scaffold can maintain round morphology and synthesize extracellular matrix to induce regeneration of hyaline cartilage microtissues by geometrical restriction. A series of M PCM-like scaffolds was fabricated with different stiffness and those with a high Young's modulus are more effective in maintaining the chondrocyte phenotype. The proposed PCM-like scaffolds are effective in modulating cartilage formation influenced by pore size, depth and stiffness, which would pave the way for a better understanding of the geometric cues of mechanotransduction interactions in regulating cell fate and open up new avenues for tissue engineering. This article is protected by copyright. All rights reserved.", "classifications": [ { "id": "Fujita", "label": "Group Fujita", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Teng", "last_name": "Li", "name": null }, { "creator_type": "author", "first_name": "Jie", "last_name": "Liu", "name": null }, { "creator_type": "author", "first_name": "Min", "last_name": "Guo", "name": null }, { "creator_type": "author", "first_name": "Fan-Chun", "last_name": "Bin", "name": null }, { "creator_type": "author", "first_name": "Qi", "last_name": "Duan", "name": null }, { "creator_type": "author", "first_name": "Xian-Zi", "last_name": "Dong", "name": null }, { "creator_type": "author", "first_name": "Feng", "last_name": "Jin", "name": null }, { "creator_type": "author", "first_name": "Katsumasa", "last_name": "Fujita", "name": null }, { "creator_type": "author", "first_name": "Mei-Ling", "last_name": "Zheng", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/adhm.202400849" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "38687974" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cattle", "descriptor_ui": "D002417", "major_topic": false }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Chondrocytes", "descriptor_ui": "D019902", "major_topic": true }, { "descriptor": "Chondrogenesis", "descriptor_ui": "D020219", "major_topic": false }, { "descriptor": "Elastic Modulus", "descriptor_ui": "D055119", "major_topic": false }, { "descriptor": "Extracellular Matrix", "descriptor_ui": "D005109", "major_topic": true }, { "descriptor": "Hydrogels", "descriptor_ui": "D020100", "major_topic": true }, { "descriptor": "Lasers", "descriptor_ui": "D007834", "major_topic": false }, { "descriptor": "Phenotype", "descriptor_ui": "D010641", "major_topic": false }, { "descriptor": "Tissue Engineering", "descriptor_ui": "D023822", "major_topic": true }, { "descriptor": "Tissue Scaffolds", "descriptor_ui": "D054457", "major_topic": true } ], "publication": { "conference_name": null, "date": "2024 Apr 30", "date_precision": "day", "issue": "", "normalized_date": "2024-04-30", "pages": "e2400849", "proceedings_title": null, "publisher": "", "title": "Advanced healthcare materials", "volume": "", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Femtosecond Laser Maskless Optical Projection Lithography of Cartilage PCM Inspired 3D Protein Matrix to Chondrocyte Phenotype.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Tissue regeneration and maintenance rely on coordinated stem cell behaviours. This orchestration can be impaired by oncogenic mutations leading to cancer. However, it is largely unclear how oncogenes perturb stem cells' orchestration to disrupt tissue. Here we used intravital imaging to investigate the mechanisms by which oncogenic Kras mutation causes tissue disruption in the hair follicle. Through longitudinally tracking hair follicles in live mice, we found that Kras(G12D), a mutation that can lead to squamous cell carcinoma, induces epithelial tissue deformation in a spatiotemporally specific manner, linked with abnormal cell division and migration. Using a reporter mouse capture real-time ERK signal dynamics at the single-cell level, we discovered that Kras(G12D), but not a closely related mutation Hras(G12V), converts ERK signal in stem cells from pulsatile to sustained. Finally, we demonstrated that interrupting sustained ERK signal reverts Kras(G12D)-induced tissue deformation through modulating specific features of cell migration and division.", "classifications": [ { "id": "Fujiwara", "label": "Group Fujiwara", "parent": "Fujiwara", "type": "group" }, { "id": "Fujiwara", "label": "Team Fujiwara", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Tianchi", "last_name": "Xin", "name": null }, { "creator_type": "author", "first_name": "Sara", "last_name": "Gallini", "name": null }, { "creator_type": "author", "first_name": "Haoyang", "last_name": "Wei", "name": null }, { "creator_type": "author", "first_name": "David G.", "last_name": "Gonzalez", "name": null }, { "creator_type": "author", "first_name": "Catherine", "last_name": "Matte-Martone", "name": null }, { "creator_type": "author", "first_name": "Hiroki", "last_name": "Machida", "name": null }, { "creator_type": "author", "first_name": "Hironobu", "last_name": "Fujiwara", "name": null }, { "creator_type": "author", "first_name": "H. Amalia", "last_name": "Pasolli", "name": null }, { "creator_type": "author", "first_name": "Kathleen C.", "last_name": "Suozzi", "name": null }, { "creator_type": "author", "first_name": "Lauren E.", "last_name": "Gonzalez", "name": null }, { "creator_type": "author", "first_name": "Sergi", "last_name": "Regot", "name": null }, { "creator_type": "author", "first_name": "Valentina", "last_name": "Greco", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41556-024-01413-y" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "38689013" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Carcinoma, Squamous Cell", "descriptor_ui": "D002294", "major_topic": false }, { "descriptor": "Cell Movement", "descriptor_ui": "D002465", "major_topic": true }, { "descriptor": "Enzyme Activation", "descriptor_ui": "D004789", "major_topic": false }, { "descriptor": "Extracellular Signal-Regulated MAP Kinases", "descriptor_ui": "D048049", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Hair Follicle", "descriptor_ui": "D018859", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "MAP Kinase Signaling System", "descriptor_ui": "D020935", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Transgenic", "descriptor_ui": "D008822", "major_topic": false }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": true }, { "descriptor": "Proto-Oncogene Proteins p21(ras)", "descriptor_ui": "D016283", "major_topic": true }, { "descriptor": "Stem Cells", "descriptor_ui": "D013234", "major_topic": false } ], "publication": { "conference_name": null, "date": "2024 Apr 30", "date_precision": "day", "issue": "", "normalized_date": "2024-04-30", "pages": "", "proceedings_title": null, "publisher": "", "title": "Nature cell biology", "volume": "", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Oncogenic Kras induces spatiotemporally specific tissue deformation through converting pulsatile into sustained ERK activation.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Seasonal changes in spring induce flowering by expressing the florigen, FLOWERING LOCUS T (FT), in Arabidopsis. FT is expressed in unique phloem companion cells with unknown characteristics. The question of which genes are co-expressed with FT and whether they have roles in flowering remains elusive. Through tissue-specific translatome analysis, we discovered that under long-day conditions with the natural sunlight red/far-red ratio, the FT-producing cells express a gene encoding FPF1-LIKE PROTEIN 1 (FLP1). The master FT regulator, CONSTANS (CO), controls FLP1 expression, suggesting FLP1's involvement in the photoperiod pathway. FLP1 promotes early flowering independently of FT, is active in the shoot apical meristem, and induces the expression of SEPALLATA 3 (SEP3), a key E-class homeotic gene. Unlike FT, FLP1 facilitates inflorescence stem elongation. Our cumulative evidence indicates that FLP1 may act as a mobile signal. Thus, FLP1 orchestrates floral initiation together with FT and promotes inflorescence stem elongation during reproductive transitions.", "classifications": [ { "id": "Sato", "label": "Group Sato", "parent": "Tsuchiya", "type": "group" }, { "id": "Tsuchiya", "label": "Team Tsuchiya", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Takagi", "name": null }, { "creator_type": "author", "first_name": "Nayoung", "last_name": "Lee", "name": null }, { "creator_type": "author", "first_name": "Andrew K.", "last_name": "Hempton", "name": null }, { "creator_type": "author", "first_name": "Savita", "last_name": "Purushwani", "name": null }, { "creator_type": "author", "first_name": "Michitaka", "last_name": "Notaguchi", "name": null }, { "creator_type": "author", "first_name": "Kota", "last_name": "Yamauchi", "name": null }, { "creator_type": "author", "first_name": "Kazumasa", "last_name": "Shirai", "name": null }, { "creator_type": "author", "first_name": "Yaichi", "last_name": "Kawakatsu", "name": null }, { "creator_type": "author", "first_name": "Susumu", "last_name": "Uehara", "name": null }, { "creator_type": "author", "first_name": "William G.", "last_name": "Albers", "name": null }, { "creator_type": "author", "first_name": "Benjamin L. R.", "last_name": "Downing", "name": null }, { "creator_type": "author", "first_name": "Shogo", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Takamasa", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Takakazu", "last_name": "Matsuura", "name": null }, { "creator_type": "author", "first_name": "Izumi C.", "last_name": "Mori", "name": null }, { "creator_type": "author", "first_name": "Nobutaka", "last_name": "Mitsuda", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Kurihara", "name": null }, { "creator_type": "author", "first_name": "Tomonao", "last_name": "Matsushita", "name": null }, { "creator_type": "author", "first_name": "Young Hun", "last_name": "Song", "name": null }, { "creator_type": "author", "first_name": "Yoshikatsu", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Mika", "last_name": "Nomoto", "name": null }, { "creator_type": "author", "first_name": "Yasuomi", "last_name": "Tada", "name": null }, { "creator_type": "author", "first_name": "Kousuke", "last_name": "Hanada", "name": null }, { "creator_type": "author", "first_name": "Josh T.", "last_name": "Cuperus", "name": null }, { "creator_type": "author", "first_name": "Christine", "last_name": "Queitsch", "name": null }, { "creator_type": "author", "first_name": "Takato", "last_name": "Imaizumi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1101/2024.04.26.591289" }, "pmcid": { "normalized": null }, "pmid": { "normalized": null } }, "mesh": [], "publication": { "conference_name": null, "date": "2024 Apr 29", "date_precision": "day", "issue": null, "normalized_date": "2024-04-29", "pages": null, "proceedings_title": null, "publisher": null, "title": null, "volume": null, "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Florigen-producing cells express FPF1-LIKE PROTEIN 1 that accelerates flowering and stem growth in long days with sunlight red/far-red ratio in Arabidopsis.", "url": "", "zotero": { "item_type": "preprint" } }, { "abstract": "Human-induced pluripotent stem cells (hiPSCs) have great therapeutic potential. The cell source differentiated from hiPSCs requires xeno-free and robust methods for lineage-specific differentiation. Here, a system is described for differentiating hiPSCs on new generation laminin fragments (NGLFs), a recombinant form of a laminin E8 fragment conjugated to the heparan sulfate chains (HS) attachment domain of perlecan. Using NGLFs, hiPSCs are highly promoted to direct differentiation into a paraxial mesoderm state with high-efficiency muscle lineage generation. HS conjugation to the C-terminus of Laminin E8 fragments brings fibroblast growth factors (FGFs) bound to the HS close to the cell surface of hiPSCs, thereby facilitating stronger FGF signaling pathways stimulation and initiating HOX gene expression, which triggers the paraxial mesoderm differentiation of hiPSCs. This highly efficient differentiation system can provide a roadmap for paraxial mesoderm development and an infinite source of myocytes and muscle stem cells for disease modeling and regenerative medicine.", "classifications": [ { "id": "Yamamoto", "label": "Group Yamamoto", "parent": "Toyoshima", "type": "group" }, { "id": "Toyoshima", "label": "Team Toyoshima", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Mingming", "last_name": "Zhao", "name": null }, { "creator_type": "author", "first_name": "Yukimasa", "last_name": "Taniguchi", "name": null }, { "creator_type": "author", "first_name": "Chisei", "last_name": "Shimono", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Jonouchi", "name": null }, { "creator_type": "author", "first_name": "Yushen", "last_name": "Cheng", "name": null }, { "creator_type": "author", "first_name": "Yasuhiro", "last_name": "Shimizu", "name": null }, { "creator_type": "author", "first_name": "Minas", "last_name": "Nalbandian", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Masato", "last_name": "Nakagawa", "name": null }, { "creator_type": "author", "first_name": "Kiyotoshi", "last_name": "Sekiguchi", "name": null }, { "creator_type": "author", "first_name": "Hidetoshi", "last_name": "Sakurai", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/advs.202308306" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "38685581" } }, "mesh": [ { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": true }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Heparan Sulfate", "descriptor_ui": "D006497", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Induced Pluripotent Stem Cells", "descriptor_ui": "D057026", "major_topic": true }, { "descriptor": "Laminin", "descriptor_ui": "D007797", "major_topic": true }, { "descriptor": "Mesoderm", "descriptor_ui": "D008648", "major_topic": true }, { "descriptor": "Muscle Development", "descriptor_ui": "D024510", "major_topic": false } ], "publication": { "conference_name": null, "date": "2024 Apr 29", "date_precision": "day", "issue": "", "normalized_date": "2024-04-29", "pages": "e2308306", "proceedings_title": null, "publisher": "", "title": "Advanced science (Weinheim, Baden-Wurttemberg, Germany)", "volume": "", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Heparan Sulfate Chain-Conjugated Laminin-E8 Fragments Advance Paraxial Mesodermal Differentiation Followed by High Myogenic Induction from hiPSCs.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The heart of ascidians, marine invertebrate chordates, has a tubular structure, and heartbeats propagate from one end to the other. The direction of pulsation waves intermittently reverses in the heart of ascidians and their relatives; however, the underlying mechanisms remain unclear. We herein performed a series of experiments to characterize the pacemaker systems in isolated hearts and their fragments, and applied a mathematical model to examine the conditions leading to heart reversals. The isolated heart of Ciona autonomously generated pulsation waves at approximately 20 to 25 beats per minute (bpm) with reversals at approximately 1 to 10 min intervals. Experimental bisections of isolated hearts revealed that independent pacemakers resided on each side and also that their beating frequencies periodically changed as they expressed bimodal rhythms, which comprised an approximately 1.25 to 5.5-min acceleration/deceleration cycle of a beating rate of between 0 and 25 bpm. Only fragments including 5% or shorter terminal regions of the heart tube maintained autonomous pulsation rhythms, whereas other regions did not. Our mathematical model, based on FitzHugh-Nagumo equations applied to a one-dimensional alignment of cells, demonstrated that the difference between frequencies expressed by the two independent terminal pacemakers determined the direction of propagated waves. Changes in the statuses of terminal pacemakers between the excitatory and oscillatory modes as well as in their endogenous oscillation frequencies were sufficient to lead to heart reversals. These results suggest that the directions of pulsation waves in the Ciona heart reverse according to the changing rhythms independently expressed by remotely coupled terminal pacemakers.", "classifications": [ { "id": "Fujimoto", "label": "Group Fujimoto", "parent": "Ueda", "type": "group" }, { "id": "Ueda", "label": "Team Ueda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yuma", "last_name": "Fujikake", "name": null }, { "creator_type": "author", "first_name": "Keita", "last_name": "Fukuda", "name": null }, { "creator_type": "author", "first_name": "Katsuyoshi", "last_name": "Matsushita", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Iwatani", "name": null }, { "creator_type": "author", "first_name": "Koichi", "last_name": "Fujimoto", "name": null }, { "creator_type": "author", "first_name": "Atsuo S.", "last_name": "Nishino", "name": null } ], "identifiers": { "doi": { "normalized": "10.1242/jeb.246810" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "38682233" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Biological Clocks", "descriptor_ui": "D001683", "major_topic": true }, { "descriptor": "Ciona intestinalis", "descriptor_ui": "D002938", "major_topic": true }, { "descriptor": "Heart", "descriptor_ui": "D006321", "major_topic": true }, { "descriptor": "Heart Rate", "descriptor_ui": "D006339", "major_topic": false } ], "publication": { "conference_name": null, "date": "2024 Apr 29", "date_precision": "day", "issue": "", "normalized_date": "2024-04-29", "pages": "jeb.246810", "proceedings_title": null, "publisher": "", "title": "The Journal of experimental biology", "volume": "", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Pulsation waves along the Ciona heart tube reverse by bimodal rhythms expressed by a remote pair of pacemakers.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Protein lactylation is a post-translational modification associated with glycolysis. Although recent evidence indicates that protein lactylation is involved in epigenetic gene regulation, its pathophysiological significance remains unclear, particularly in neoplasms. Herein, we investigated the potential involvement of protein lactylation in the molecular mechanisms underlying benign and malignant pancreatic epithelial tumors, as well as its role in the response of pancreatic cancer (PC) cells to gemcitabine. Increased lactylation was observed in the nuclei of intraductal papillary mucinous adenoma, non-invasive intraductal papillary mucinous carcinoma, and invasive carcinoma, in parallel to the upregulation of hypoxia-inducible factor-1α. This observation indicated that a hypoxia-associated increase in nuclear protein lactylation could be a biochemical hallmark in pancreatic epithelial tumors. The standard PC chemotherapy drug gemcitabine suppressed histone lactylation in vitro, suggesting that histone lactylation might be relevant to its mechanism of action. Taken together, our findings suggest that protein lactylation may be involved in the development of pancreatic epithelial tumors and could represent a potential therapeutic target for PC.", "classifications": [ { "id": "JPMJCR1925", "label": "JPMJCR1925", "researcher": "Katsumasa Fujita", "type": "grant" }, { "id": "Fujita", "label": "Group Fujita", "parent": "Fujita", "type": "group" }, { "id": "Tanaka", "label": "Group Tanaka", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Tomoki", "last_name": "Takata", "name": null }, { "creator_type": "author", "first_name": "Akihiro", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Hiroaki", "last_name": "Yasuda", "name": null }, { "creator_type": "author", "first_name": "Hayato", "last_name": "Miyake", "name": null }, { "creator_type": "author", "first_name": "Yoshio", "last_name": "Sogame", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Sawai", "name": null }, { "creator_type": "author", "first_name": "Michiyo", "last_name": "Hayakawa", "name": null }, { "creator_type": "author", "first_name": "Kentaro", "last_name": "Mochizuki", "name": null }, { "creator_type": "author", "first_name": "Ryuta", "last_name": "Nakao", "name": null }, { "creator_type": "author", "first_name": "Takehiro", "last_name": "Ogata", "name": null }, { "creator_type": "author", "first_name": "Hisashi", "last_name": "Ikoma", "name": null }, { "creator_type": "author", "first_name": "Eiichi", "last_name": "Konishi", "name": null }, { "creator_type": "author", "first_name": "Yoshinori", "last_name": "Harada", "name": null }, { "creator_type": "author", "first_name": "Eigo", "last_name": "Otsuji", "name": null }, { "creator_type": "author", "first_name": "Yoshito", "last_name": "Itoh", "name": null }, { "creator_type": "author", "first_name": "Hideo", "last_name": "Tanaka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1267/ahc.24-00010" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "38695038" } }, "mesh": [], "publication": { "conference_name": null, "date": "2024 Apr 25", "date_precision": "day", "issue": "2", "normalized_date": "2024-04-25", "pages": "57-66", "proceedings_title": null, "publisher": "", "title": "Acta Histochemica et Cytochemica", "volume": "57", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Pathophysiological Implications of Protein Lactylation in Pancreatic Epithelial Tumors.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Daichi", "last_name": "Morii", "name": null }, { "creator_type": "author", "first_name": "Takahiro", "last_name": "Matsui", "name": null }, { "creator_type": "author", "first_name": "Taisuke", "last_name": "Mori", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null }, { "creator_type": "author", "first_name": "Eiichi", "last_name": "Morii", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/pin.13431" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "38651939" } }, "mesh": [ { "descriptor": "Gliosis", "descriptor_ui": "D005911", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Infant", "descriptor_ui": "D007223", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Metaplasia", "descriptor_ui": "D008679", "major_topic": true }, { "descriptor": "Ossification, Heterotopic", "descriptor_ui": "D009999", "major_topic": false }, { "descriptor": "Retina", "descriptor_ui": "D012160", "major_topic": false }, { "descriptor": "Retinal Diseases", "descriptor_ui": "D012164", "major_topic": false } ], "publication": { "conference_name": null, "date": "2024 Apr 23", "date_precision": "day", "issue": "", "normalized_date": "2024-04-23", "pages": "", "proceedings_title": null, "publisher": "", "title": "Pathology international", "volume": "", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Retinal gliosis with osseous metaplasia in an infant.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Raman spectroscopy can provide nonbiased single-cell analysis based on the endogenous ensemble of biomolecules, with alterations in cellular content indicative of cell state and disease. The measurements themselves can be performed in a variety of modes: generally, full imaging takes the most time but can provide the most information. By reducing the imaging resolution and generating the most characteristic single-cell Raman spectrum in the shortest time, we optimize the utility of the Raman measurement for cell phenotyping. Here, we establish methods to compare these different measurement approaches and assess what, if any, undesired effects occur in the cell. Assuming that laser-induced damage should be apparent as a change in molecular spectra across sequential measurements, and by defining the information content as the Raman-based separability of two cell lines, we thereby establish a parameter range for optimum measurement sensitivity and single-cell throughput in single-cell Raman spectroscopic analysis. While the work here uses 532 nm irradiation, the same approach can be generalized to Raman analysis at other wavelengths.", "classifications": [ { "id": "Fujita", "label": "Group Fujita", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Alison J.", "last_name": "Hobro", "name": null }, { "creator_type": "author", "first_name": "Nicolas", "last_name": "Pavillon", "name": null }, { "creator_type": "author", "first_name": "Kota", "last_name": "Koike", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Sugiyama", "name": null }, { "creator_type": "author", "first_name": "Takayuki", "last_name": "Umakoshi", "name": null }, { "creator_type": "author", "first_name": "Prabhat", "last_name": "Verma", "name": null }, { "creator_type": "author", "first_name": "Katsumasa", "last_name": "Fujita", "name": null }, { "creator_type": "author", "first_name": "Nicholas I.", "last_name": "Smith", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/acs.analchem.4c00236" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "38653469" } }, "mesh": [ { "descriptor": "High-Throughput Screening Assays", "descriptor_ui": "D057166", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Phenotype", "descriptor_ui": "D010641", "major_topic": false }, { "descriptor": "Single-Cell Analysis", "descriptor_ui": "D059010", "major_topic": true }, { "descriptor": "Spectrum Analysis, Raman", "descriptor_ui": "D013059", "major_topic": true } ], "publication": { "conference_name": null, "date": "2024 Apr 23", "date_precision": "day", "issue": "", "normalized_date": "2024-04-23", "pages": "", "proceedings_title": null, "publisher": "", "title": "Analytical chemistry", "volume": "", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Imaging vs Nonimaging Raman Spectroscopy for High-Throughput Single-Cell Phenotyping.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Ovarian clear cell carcinoma (OCCC) is a gynecological cancer with a dismal prognosis; however, the mechanism underlying OCCC chemoresistance is not well understood. To explore the intracellular networks associated with the chemoresistance, we analyze surgical specimens by performing integrative analyses that combine single-cell analyses and spatial transcriptomics. We find that a chemoresistant OCCC subpopulation with elevated HIF activity localizes mainly in areas populated by cancer-associated fibroblasts (CAFs) with a myofibroblastic phenotype, which is corroborated by quantitative immunostaining. CAF-enhanced chemoresistance and HIF-1alpha induction are recapitulated in co-culture assays, which show that cancer-derived platelet-derived growth factor (PDGF) contributes to the chemoresistance and HIF-1alpha induction via PDGF receptor signaling in CAFs. Ripretinib is identified as an effective receptor tyrosine kinase inhibitor against CAF survival. In the co-culture system and xenograft tumors, ripretinib prevents CAF survival and suppresses OCCC proliferation in the presence of carboplatin, indicating that combination of conventional chemotherapy and CAF-targeted agents is effective against OCCC.", "classifications": [ { "id": "Okamoto", "label": "Group Okamoto", "parent": "Okamoto", "type": "group" }, { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yutaro", "last_name": "Mori", "name": null }, { "creator_type": "author", "first_name": "Yoshie", "last_name": "Okimoto", "name": null }, { "creator_type": "author", "first_name": "Hiroaki", "last_name": "Sakai", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Kanda", "name": null }, { "creator_type": "author", "first_name": "Hirokazu", "last_name": "Ohata", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Shiokawa", "name": null }, { "creator_type": "author", "first_name": "Mikiko", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Haruka", "last_name": "Ueda", "name": null }, { "creator_type": "author", "first_name": "Tomoyuki", "last_name": "Sekizuka", "name": null }, { "creator_type": "author", "first_name": "Ryo", "last_name": "Tamura", "name": null }, { "creator_type": "author", "first_name": "Kaoru", "last_name": "Yamawaki", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Ishiguro", "name": null }, { "creator_type": "author", "first_name": "Raul Nicolas", "last_name": "Mateos", "name": null }, { "creator_type": "author", "first_name": "Yuichi", "last_name": "Shiraishi", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null }, { "creator_type": "author", "first_name": "Akinobu", "last_name": "Hamada", "name": null }, { "creator_type": "author", "first_name": "Kosuke", "last_name": "Yoshihara", "name": null }, { "creator_type": "author", "first_name": "Takayuki", "last_name": "Enomoto", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Okamoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.xcrm.2024.101532" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "38670097" } }, "mesh": [ { "descriptor": "Adenocarcinoma, Clear Cell", "descriptor_ui": "D018262", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cancer-Associated Fibroblasts", "descriptor_ui": "D000072645", "major_topic": true }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Cell Proliferation", "descriptor_ui": "D049109", "major_topic": false }, { "descriptor": "Coculture Techniques", "descriptor_ui": "D018920", "major_topic": false }, { "descriptor": "Disease Progression", "descriptor_ui": "D018450", "major_topic": false }, { "descriptor": "Drug Resistance, Neoplasm", "descriptor_ui": "D019008", "major_topic": false }, { "descriptor": "Feedback, Physiological", "descriptor_ui": "D025461", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Hypoxia-Inducible Factor 1, alpha Subunit", "descriptor_ui": "D051795", "major_topic": true }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Nude", "descriptor_ui": "D008819", "major_topic": false }, { "descriptor": "Ovarian Neoplasms", "descriptor_ui": "D010051", "major_topic": true }, { "descriptor": "Platelet-Derived Growth Factor", "descriptor_ui": "D010982", "major_topic": true }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": true }, { "descriptor": "Xenograft Model Antitumor Assays", "descriptor_ui": "D023041", "major_topic": false } ], "publication": { "conference_name": null, "date": "2024 Apr 23", "date_precision": "day", "issue": "", "normalized_date": "2024-04-23", "pages": "101532", "proceedings_title": null, "publisher": "", "title": "Cell reports. Medicine", "volume": "", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Targeting PDGF signaling of cancer-associated fibroblasts blocks feedback activation of HIF-1alpha and tumor progression of clear cell ovarian cancer.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Heterogeneity among both primed and naive pluripotent stem cell lines remains a major unresolved problem. Here we show that expressing the maternal-specific linker histone H1FOO fused to a destabilizing domain (H1FOO-DD), together with OCT4, SOX2, KLF4, and LMYC, in human somatic cells improves the quality of reprogramming to both primed and naive pluripotency. H1FOO-DD expression was associated with altered chromatin accessibility around pluripotency genes and with suppression of the innate immune response. Notably, H1FOO-DD generates naive induced pluripotent stem cells with lower variation in transcriptome and methylome among clones and a more uniform and superior differentiation potency. Furthermore, we elucidated that upregulation of FKBP1A, driven by these five factors, plays a key role in H1FOO-DD-mediated reprogramming.", "classifications": [ { "id": "Yamamoto", "label": "Group Yamamoto", "parent": "Toyoshima", "type": "group" }, { "id": "Toyoshima", "label": "Team Toyoshima", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Akira", "last_name": "Kunitomi", "name": null }, { "creator_type": "author", "first_name": "Ryoko", "last_name": "Hirohata", "name": null }, { "creator_type": "author", "first_name": "Mitsujiro", "last_name": "Osawa", "name": null }, { "creator_type": "author", "first_name": "Kaho", "last_name": "Washizu", "name": null }, { "creator_type": "author", "first_name": "Vanessa", "last_name": "Arreola", "name": null }, { "creator_type": "author", "first_name": "Norikazu", "last_name": "Saiki", "name": null }, { "creator_type": "author", "first_name": "Tomoaki M.", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Masaki", "last_name": "Nomura", "name": null }, { "creator_type": "author", "first_name": "Haruko", "last_name": "Kunitomi", "name": null }, { "creator_type": "author", "first_name": "Tokiko", "last_name": "Ohkame", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Ohkame", "name": null }, { "creator_type": "author", "first_name": "Jitsutaro", "last_name": "Kawaguchi", "name": null }, { "creator_type": "author", "first_name": "Hiroto", "last_name": "Hara", "name": null }, { "creator_type": "author", "first_name": "Kohji", "last_name": "Kusano", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Yasuhiro", "last_name": "Takashima", "name": null }, { "creator_type": "author", "first_name": "Shugo", "last_name": "Tohyama", "name": null }, { "creator_type": "author", "first_name": "Shinsuke", "last_name": "Yuasa", "name": null }, { "creator_type": "author", "first_name": "Keiichi", "last_name": "Fukuda", "name": null }, { "creator_type": "author", "first_name": "Naoko", "last_name": "Takasu", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Yamanaka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.stemcr.2024.04.005" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "38701780" } }, "mesh": [ { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Cellular Reprogramming", "descriptor_ui": "D065150", "major_topic": true }, { "descriptor": "Chromatin", "descriptor_ui": "D002843", "major_topic": false }, { "descriptor": "Histones", "descriptor_ui": "D006657", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Induced Pluripotent Stem Cells", "descriptor_ui": "D057026", "major_topic": true }, { "descriptor": "Kruppel-Like Factor 4", "descriptor_ui": "D000090062", "major_topic": true }, { "descriptor": "Kruppel-Like Transcription Factors", "descriptor_ui": "D051741", "major_topic": false }, { "descriptor": "Pluripotent Stem Cells", "descriptor_ui": "D039904", "major_topic": false }, { "descriptor": "SOXB1 Transcription Factors", "descriptor_ui": "D055748", "major_topic": false }, { "descriptor": "Transcription Factors", "descriptor_ui": "D014157", "major_topic": false }, { "descriptor": "Transcriptome", "descriptor_ui": "D059467", "major_topic": false } ], "publication": { "conference_name": null, "date": "2024 Apr 23", "date_precision": "day", "issue": "", "normalized_date": "2024-04-23", "pages": "S2213-6711(24)00111-5", "proceedings_title": null, "publisher": "", "title": "Stem cell reports", "volume": "", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "H1FOO-DD promotes efficiency and uniformity in reprogramming to naive pluripotency.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Malignant tumors are characterized by a hypoxic microenvironment, and metabolic reprogramming is necessary to ensure energy production and oxidative stress resistance. Although the microenvironmental properties of tumors vary under acute and chronic hypoxia, studies on chronic hypoxia-induced metabolic changes are limited. In the present study, we performed a comprehensive metabolic analysis in a chronic hypoxia model using colorectal cancer (CRC) organoids, and identified an amino acid supply system through the gamma-glutamyl cycle, a glutathione recycling pathway. We analyzed the metabolic changes caused by hypoxia over time and observed that chronic hypoxia resulted in an increase in 5-oxoproline and a decrease in oxidized glutathione (GSSG) compared to acute hypoxia. These findings suggest that chronic hypoxia induces metabolic changes in the gamma-glutamyl cycle. Moreover, inhibition of the gamma-glutamyl cycle via gamma-glutamyl cyclotransferase (GGCT) and gamma-glutamyl transferase 1 (GGT1) knockdown significantly reversed chronic hypoxia-induced upregulation of 5-oxoproline and several amino acids. Notably, GGT1 knockdown downregulated the intracellular levels of gamma-glutamyl amino acids. Conclusively, these results indicate that the gamma-glutamyl cycle serves as an amino acid supply system in CRC under chronic hypoxia, which provides fresh insight into cancer metabolism under chronic hypoxia.", "classifications": [ { "id": "JPMJCR2123", "label": "JPMJCR2123", "researcher": "Shinya Kuroda", "type": "grant" }, { "id": "Kuroda", "label": "Group Kuroda", "parent": "Kuroda", "type": "group" }, { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Sho", "last_name": "Tabata", "name": null }, { "creator_type": "author", "first_name": "Hiroko", "last_name": "Endo", "name": null }, { "creator_type": "author", "first_name": "Hideki", "last_name": "Makinoshima", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Inoue", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.bbrc.2024.149977" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "38663093" } }, "mesh": [ { "descriptor": "Amino Acids", "descriptor_ui": "D000596", "major_topic": true }, { "descriptor": "Cell Hypoxia", "descriptor_ui": "D015687", "major_topic": false }, { "descriptor": "Colorectal Neoplasms", "descriptor_ui": "D015179", "major_topic": true }, { "descriptor": "gamma-Glutamylcyclotransferase", "descriptor_ui": "D005722", "major_topic": false }, { "descriptor": "gamma-Glutamyltransferase", "descriptor_ui": "D005723", "major_topic": true }, { "descriptor": "Glutathione", "descriptor_ui": "D005978", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Hypoxia", "descriptor_ui": "D000860", "major_topic": false }, { "descriptor": "Organoids", "descriptor_ui": "D009940", "major_topic": true }, { "descriptor": "Tumor Hypoxia", "descriptor_ui": "D000072258", "major_topic": false }, { "descriptor": "Tumor Microenvironment", "descriptor_ui": "D059016", "major_topic": false } ], "publication": { "conference_name": null, "date": "2024 Apr 22", "date_precision": "day", "issue": "", "normalized_date": "2024-04-22", "pages": "149977", "proceedings_title": null, "publisher": "", "title": "Biochemical and biophysical research communications", "volume": "714", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "The gamma-glutamyl cycle serves as an amino acids supply system in colorectal cancer organoids under chronic hypoxia.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "During organ regeneration, after the initial responses to injury, gene expression patterns similar to those in normal development are reestablished during subsequent morphogenesis phases. This supports the idea that regeneration recapitulates development and predicts the existence of genes that reboot the developmental program after the initial responses. However, such rebooting mechanisms are largely unknown. Here, we explore core rebooting factors that operate during Xenopus limb regeneration. Transcriptomic analysis of larval limb blastema reveals that hoxc12/c13 show the highest regeneration specificity in expression. Knocking out each of them through genome editing inhibits cell proliferation and expression of a group of genes that are essential for development, resulting in autopod regeneration failure, while limb development and initial blastema formation are not affected. Furthermore, the induction of hoxc12/c13 expression partially restores froglet regenerative capacity which is normally very limited compared to larval regeneration. Thus, we demonstrate the existence of genes that have a profound impact alone on rebooting of the developmental program in a regeneration-specific manner.", "classifications": [ { "id": "JPMJCR2025", "label": "JPMJCR2025", "researcher": "Yoshihiro Morishita", "type": "grant" }, { "id": "Morishita", "label": "Group Morishita", "parent": "Morishita", "type": "group" }, { "id": "Suzuki", "label": "Group Suzuki", "parent": "Morishita", "type": "group" }, { "id": "Morishita", "label": "Team Morishita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Aiko", "last_name": "Kawasumi-Kita", "name": null }, { "creator_type": "author", "first_name": "Sang-Woo", "last_name": "Lee", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Ohtsuka", "name": null }, { "creator_type": "author", "first_name": "Kaori", "last_name": "Niimi", "name": null }, { "creator_type": "author", "first_name": "Yoshifumi", "last_name": "Asakura", "name": null }, { "creator_type": "author", "first_name": "Keiichi", "last_name": "Kitajima", "name": null }, { "creator_type": "author", "first_name": "Yuto", "last_name": "Sakane", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Tamura", "name": null }, { "creator_type": "author", "first_name": "Haruki", "last_name": "Ochi", "name": null }, { "creator_type": "author", "first_name": "Ken-Ichi T.", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Yoshihiro", "last_name": "Morishita", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41467-024-47093-y" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "38649703" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Proliferation", "descriptor_ui": "D049109", "major_topic": false }, { "descriptor": "Extremities", "descriptor_ui": "D005121", "major_topic": true }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Gene Editing", "descriptor_ui": "D000072669", "major_topic": false }, { "descriptor": "Gene Expression Profiling", "descriptor_ui": "D020869", "major_topic": false }, { "descriptor": "Gene Expression Regulation, Developmental", "descriptor_ui": "D018507", "major_topic": true }, { "descriptor": "Homeodomain Proteins", "descriptor_ui": "D018398", "major_topic": true }, { "descriptor": "Larva", "descriptor_ui": "D007814", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Regeneration", "descriptor_ui": "D012038", "major_topic": true }, { "descriptor": "Xenopus laevis", "descriptor_ui": "D014982", "major_topic": true }, { "descriptor": "Xenopus Proteins", "descriptor_ui": "D029867", "major_topic": true } ], "publication": { "conference_name": null, "date": "2024 Apr 22", "date_precision": "day", "issue": "1", "normalized_date": "2024-04-22", "pages": "3340", "proceedings_title": null, "publisher": "", "title": "Nature communications", "volume": "15", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "hoxc12/c13 as key regulators for rebooting the developmental program in Xenopus limb regeneration.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19), which is associated with various neurological symptoms, including nausea, dizziness, headache, encephalitis, and epileptic seizures. SARS-CoV-2 is considered to affect the central nervous system (CNS) by interacting with the blood-brain barrier (BBB), which is defined by tight junctions that seal paracellular gaps between brain microvascular endothelial cells (BMECs). Although SARS-CoV-2 infection of BMECs has been reported, the detailed mechanism has not been fully elucidated. METHODS: Using the original strain of SARS-CoV-2, the infection in BMECs was confirmed by a detection of intracellular RNA copy number and localization of viral particles. BMEC functions were evaluated by measuring transendothelial electrical resistance (TEER), which evaluates the integrity of tight junction dynamics, and expression levels of proinflammatory genes. BMEC signaling pathway was examined by comprehensive RNA-seq analysis. RESULTS: We observed that iPSC derived brain microvascular endothelial like cells (iPSC-BMELCs) were infected with SARS-CoV-2. SARS-CoV-2 infection resulted in decreased TEER. In addition, SARS-CoV-2 infection decreased expression levels of tight junction markers CLDN3 and CLDN11. SARS-CoV-2 infection also increased expression levels of proinflammatory genes, which are known to be elevated in patients with COVID-19. Furthermore, RNA-seq analysis revealed that SARS-CoV-2 dysregulated the canonical Wnt signaling pathway in iPSC-BMELCs. Modulation of the Wnt signaling by CHIR99021 partially inhibited the infection and the subsequent inflammatory responses. CONCLUSION: These findings suggest that SARS-CoV-2 infection causes BBB dysfunction via Wnt signaling. Thus, iPSC-BMELCs are a useful in vitro model for elucidating COVID-19 neuropathology and drug development.", "classifications": [ { "id": "Nishida", "label": "Group Nishida", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Shigeru", "last_name": "Yamada", "name": null }, { "creator_type": "author", "first_name": "Tadahiro", "last_name": "Hashita", "name": null }, { "creator_type": "author", "first_name": "Shota", "last_name": "Yanagida", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Yukuto", "last_name": "Yasuhiko", "name": null }, { "creator_type": "author", "first_name": "Kaori", "last_name": "Okabe", "name": null }, { "creator_type": "author", "first_name": "Takamasa", "last_name": "Noda", "name": null }, { "creator_type": "author", "first_name": "Motohiro", "last_name": "Nishida", "name": null }, { "creator_type": "author", "first_name": "Tamihide", "last_name": "Matsunaga", "name": null }, { "creator_type": "author", "first_name": "Yasunari", "last_name": "Kanda", "name": null } ], "identifiers": { "doi": { "normalized": "10.1186/s12987-024-00533-9" }, "pmcid": { "normalized": "PMC11000354" }, "pmid": { "normalized": "38584257" } }, "mesh": [ { "descriptor": "Blood-Brain Barrier", "descriptor_ui": "D001812", "major_topic": false }, { "descriptor": "Brain", "descriptor_ui": "D001921", "major_topic": false }, { "descriptor": "COVID-19", "descriptor_ui": "D000086382", "major_topic": true }, { "descriptor": "Endothelial Cells", "descriptor_ui": "D042783", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Induced Pluripotent Stem Cells", "descriptor_ui": "D057026", "major_topic": true }, { "descriptor": "SARS-CoV-2", "descriptor_ui": "D000086402", "major_topic": false }, { "descriptor": "Wnt Signaling Pathway", "descriptor_ui": "D060449", "major_topic": false } ], "publication": { "conference_name": null, "date": "2024 Apr 8", "date_precision": "day", "issue": "1", "normalized_date": "2024-04-08", "pages": "32", "proceedings_title": null, "publisher": "", "title": "Fluids and barriers of the CNS", "volume": "21", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "SARS-CoV-2 causes dysfunction in human iPSC-derived brain microvascular endothelial cells potentially by modulating the Wnt signaling pathway.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Context: Sodium-glucose cotransporter 2 (SGLT2) inhibitors lower blood glucose levels by promoting urinary glucose excretion, but their overall effects on hormonal and metabolic status remain unclear. Objective: We here investigated the roles of insulin and glucagon in the regulation of glycemia in individuals treated with an SGLT2 inhibitor using mathematical model analysis. Methods: Hyperinsulinemic-euglycemic clamp and oral glucose tolerance tests were performed in 68 individuals with type 2 diabetes treated with the SGLT2 inhibitor dapagliflozin. Data previously obtained from such tests in 120 subjects with various levels of glucose tolerance and not treated with an SGLT2 inhibitor were examined as a control. Mathematical models of the feedback loops connecting glucose and insulin (GI model) or glucose, insulin, and glucagon (GIG model) were generated. Results: Analysis with the GI model revealed that the disposition index/clearance, which is defined as the product of insulin sensitivity and insulin secretion divided by the square of insulin clearance and represents the glucose-handling ability of insulin, was significantly correlated with glycemia in subjects not taking an SGLT2 inhibitor but not in those taking dapagliflozin. Analysis with the GIG model revealed that a metric defined as the product of glucagon sensitivity and glucagon secretion divided by glucagon clearance (designated production index/clearance) was significantly correlated with blood glucose level in subjects treated with dapagliflozin. Conclusion: Treatment with an SGLT2 inhibitor alters the relation between insulin effect and blood glucose concentration, and glucagon effect may account for variation in glycemia among individuals treated with such drugs.", "classifications": [ { "id": "JPMJCR2123", "label": "JPMJCR2123", "researcher": "Shinya Kuroda", "type": "grant" }, { "id": "Kuroda", "label": "Group Kuroda", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Tomoko", "last_name": "Yamada", "name": null }, { "creator_type": "author", "first_name": "Hikaru", "last_name": "Sugimoto", "name": null }, { "creator_type": "author", "first_name": "Ken-ichi", "last_name": "Hironaka", "name": null }, { "creator_type": "author", "first_name": "Yasuko", "last_name": "Morita", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Miura", "name": null }, { "creator_type": "author", "first_name": "Natsu", "last_name": "Otowa-Suematsu", "name": null }, { "creator_type": "author", "first_name": "Yuko", "last_name": "Okada", "name": null }, { "creator_type": "author", "first_name": "Yushi", "last_name": "Hirota", "name": null }, { "creator_type": "author", "first_name": "Kazuhiko", "last_name": "Sakaguchi", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Kuroda", "name": null }, { "creator_type": "author", "first_name": "Wataru", "last_name": "Ogawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1210/jendso/bvae067" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "38633895" } }, "mesh": [], "publication": { "conference_name": null, "date": "2024 Apr 06", "date_precision": "day", "issue": "6", "normalized_date": "2024-04-06", "pages": "", "proceedings_title": null, "publisher": "", "title": "Journal of the Endocrine Society", "volume": "8", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Mathematical Models of the Effect of Glucagon on Glycemia in Individuals With Type 2 Diabetes Treated With Dapagliflozin.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "INTRODUCTION: Programmed cell death ligand-1 (PD-L1) expression is a predictive biomarker for the efficacy of anti-programmed cell death receptor-1/PD-L1 antibodies in advanced non-small cell lung cancer (NSCLC). Although several assays have been approved for evaluating PD-L1 expression status, inter-assay discordance has been observed between some assays. The clinical significance of these discrepancies is still unclear. METHODS: We retrospectively reviewed treatment-naive NSCLC patients whose PD-L1 expression was evaluated using both 22C3 and SP142 assays. Among those, efficacy analysis was performed for patients with PD-L1 tumor proportion score (TPS) >/= 50 % (22C3), who had received first-line pembrolizumab monotherapy. Additionally, transcriptome analysis was conducted in the available tumors with TPS >/= 50 % to investigate the distinct immune profiles that accompany inter-assay discordance. RESULTS: In total, 611 patients were eligible. Among 198 patients with TPS >/= 50 %, 91 (46 %) had tumor cell score T in almost all lesions, and most mutational signatures corresponded to signature 1, 2, 3, and 8. The types of proposed aetiology in most lesions were based on age and AID/APOBEC family and BRCA1/BRCA2 mutations. Evolutionary trees were characterized by short trunks and long branches due to the extremely high ratio of private mutations. In contrast, pathogenic factors, such as base substitutions, mutational signatures, and proposed aetiology, were shared. Tumour evolution in EMPD appears to be characterized by a high level of genetic ITH with shared background factors.", "classifications": [ { "id": "Suzuki", "label": "Group Suzuki", "parent": "Takekawa", "type": "group" }, { "id": "Takekawa", "label": "Team Takekawa", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Kenichiro", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Ikko", "last_name": "Kajihara", "name": null }, { "creator_type": "author", "first_name": "Kazuro", "last_name": "Shimokawa", "name": null }, { "creator_type": "author", "first_name": "Naotoshi", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Yudo", "last_name": "Kusaba", "name": null }, { "creator_type": "author", "first_name": "Ryoko", "last_name": "Sakamoto", "name": null }, { "creator_type": "author", "first_name": "Saki", "last_name": "Maeda-Otsuka", "name": null }, { "creator_type": "author", "first_name": "Saori", "last_name": "Yamada-Kanazawa", "name": null }, { "creator_type": "author", "first_name": "Soichiro", "last_name": "Sawamura", "name": null }, { "creator_type": "author", "first_name": "Hisashi", "last_name": "Kanemaru", "name": null }, { "creator_type": "author", "first_name": "Katsunari", "last_name": "Makino", "name": null }, { "creator_type": "author", "first_name": "Jun", "last_name": "Aoi", "name": null }, { "creator_type": "author", "first_name": "Shinichi", "last_name": "Masuguchi", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Fukushima", "name": null } ], "identifiers": { "doi": { "normalized": "10.1684/ejd.2024.4609" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "38907549" } }, "mesh": [ { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Aged, 80 and over", "descriptor_ui": "D000369", "major_topic": false }, { "descriptor": "Clonal Evolution", "descriptor_ui": "D060965", "major_topic": true }, { "descriptor": "Exome Sequencing", "descriptor_ui": "D000073359", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Genetic Heterogeneity", "descriptor_ui": "D018740", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": true }, { "descriptor": "Paget Disease, Extramammary", "descriptor_ui": "D010145", "major_topic": true }, { "descriptor": "Skin Neoplasms", "descriptor_ui": "D012878", "major_topic": true } ], "publication": { "conference_name": null, "date": "2024 Apr 1", "date_precision": "day", "issue": "2", "normalized_date": "2024-04-01", "pages": "182-192", "proceedings_title": null, "publisher": "", "title": "European journal of dermatology : EJD", "volume": "34", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Genetic intratumour heterogeneity and clonal evolution in extramammary Paget's disease.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The social amoeba Dictyostelium discoideum switches between solitary growth and social fruitification depending on nutrient availability. Under starvation, cells aggregate and form fruiting bodies consisting of spores and altruistic stalk cells. Once cells socially committed, they complete fruitification, even if a new source of nutrients becomes available. This social commitment is puzzling because it hinders individual cells from resuming solitary growth quickly. One idea posits that traits that facilitate premature de-commitment are hindered from being selected. We studied outcomes of the premature de-commitment through forced refeeding. Our results show that when refed cells interacted with non-refed cells, some of them became solitary, whereas a fraction was redirected to the altruistic stalk, regardless of their original fate. The refed cells exhibited reduced cohesiveness and were sorted out during morphogenesis. Our findings provide an insight into a division of labor of the social amoeba, in which less cohesive individuals become altruists.", "classifications": [ { "id": "JPMJCR1923", "label": "JPMJCR1923", "researcher": "Satoshi Sawai", "type": "grant" }, { "id": "Sawai", "label": "Group Sawai", "parent": "Sawai", "type": "group" }, { "id": "Sawai", "label": "Team Sawai", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yuka", "last_name": "Shirokawa", "name": null }, { "creator_type": "author", "first_name": "Masakazu", "last_name": "Shimada", "name": null }, { "creator_type": "author", "first_name": "Nao", "last_name": "Shimada", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Sawai", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41598-024-58277-3" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "38561423" } }, "mesh": [ { "descriptor": "Amoeba", "descriptor_ui": "D000656", "major_topic": true }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Cell Movement", "descriptor_ui": "D002465", "major_topic": false }, { "descriptor": "Dictyostelium", "descriptor_ui": "D004023", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Morphogenesis", "descriptor_ui": "D009024", "major_topic": false } ], "publication": { "conference_name": null, "date": "2024 Apr 1", "date_precision": "day", "issue": "1", "normalized_date": "2024-04-01", "pages": "7677", "proceedings_title": null, "publisher": "", "title": "Scientific reports", "volume": "14", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Prestalk-like positioning of de-differentiated cells in the social amoeba Dictyostelium discoideum.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The CRISPR-Cas system for in vivo genome editing is a powerful tool for gene therapy against several diseases. We have previously developed the pCriMGET_9-12a system, an in vivo cleavable donor plasmid for precise targeted knock-in of exogenous DNA by both Cas9 and Cas12a. Here, we show that the pCriMGET_9-12a system can be applied for in vivo in-frame knock-in of exogenous DNA in adult mouse liver by hydrodynamic delivery of the targeting plasmids. The in vivo cleavable pCriMGET_9-12a donor plasmids significantly increased the knock-in efficiency of both CRISPR-Cas9 and CRISPR-Cas12a in the adult mouse liver compared to uncleavable donor plasmids. This strategy also achieved in-frame reporter gene knock-in without indel mutations. Therefore, in vivo gene targeting using the pCriMGET_9-12a system may contribute to the establishment of safer, more precise, versatile and efficient gene therapy methods in adult organs.", "classifications": [ { "id": "JPMJCR2023", "label": "JPMJCR2023", "researcher": "Fumiko Toyoshima", "type": "grant" }, { "id": "Toyoshima", "label": "Group Toyoshima", "parent": "Toyoshima", "type": "group" }, { "id": "Toyoshima", "label": "Team Toyoshima", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Riki", "last_name": "Ishibashi", "name": null }, { "creator_type": "author", "first_name": "Ritsuko", "last_name": "Maki", "name": null }, { "creator_type": "author", "first_name": "Fumiko", "last_name": "Toyoshima", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41598-024-57551-8" }, "pmcid": { "normalized": "PMC10982285" }, "pmid": { "normalized": "38556532" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "CRISPR-Cas Systems", "descriptor_ui": "D064113", "major_topic": true }, { "descriptor": "DNA", "descriptor_ui": "D004247", "major_topic": false }, { "descriptor": "Gene Editing", "descriptor_ui": "D000072669", "major_topic": true }, { "descriptor": "Gene Targeting", "descriptor_ui": "D018390", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Plasmids", "descriptor_ui": "D010957", "major_topic": false } ], "publication": { "conference_name": null, "date": "2024 Mar 31", "date_precision": "day", "issue": "1", "normalized_date": "2024-03-31", "pages": "7615", "proceedings_title": null, "publisher": "", "title": "Scientific reports", "volume": "14", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Gene targeting in adult organs using in vivo cleavable donor plasmids for CRISPR-Cas9 and CRISPR-Cas12a.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "AIM: This study aimed to analyze two cases of marked hypo-high-density lipoprotein (HDL) cholesterolemia to identify mutations in ATP-binding cassette transporter A1 (ABCA1) and elucidate the molecular mechanism by which these novel pathological mutations contribute to hypo-HDL cholesterolemia in Tangier disease. METHODS: Wild type and mutant expression plasmids containing a FLAG tag inserted at the C-terminus of the human ABCA1 gene were generated and transfected into HEK293T cells. ABCA1 protein expression and cholesterol efflux were evaluated via Western blotting and efflux assay. The difference in the rate of change in protein expression was evaluated when proteolytic and protein-producing systems were inhibited. RESULTS: In case 1, a 20-year-old woman presented with a chief complaint of gait disturbance. Her HDL-C level was only 6.2 mg/dL. Tangier disease was suspected because of muscle weakness, decreased nerve conduction velocity, and splenomegaly. Whole-exome analysis showed compound heterozygosity for a W484* nonsense mutation and S1343I missense mutation, which confirmed Tangier disease. Cholesterol efflux decreased by a mixture of W484* and S1343I mutations. The S1343I mutation decreased the protein production rate but increased the degradation rate, decreasing the protein levels. This patient also had Krabbe disease. The endogenous ABCA1 protein level of macrophage cell decreased by knocking down its internal galactocerebrosidase.Case 2, a 51-year-old woman who underwent tonsillectomy presented with peripheral neuropathy, corneal opacity, and HDL-C of 3.4 mg/dL. Whole-exome analysis revealed compound heterozygosity for R579* and R1572* nonsense mutations, which confirmed Tangier disease. CONCLUSION: Case 1 is a new ABCA1 mutation with complex pathogenicity, namely, a W484*/S1343I compound heterozygote with marked hypo-HDL cholesterolemia. Analyses of the compound heterozygous mutations indicated that decreases in ABCA1 protein levels and cholesterol efflux activity caused by the novel S1343I mutation combined with loss of W484* protein activity could lead to marked hypo-HDL cholesterolemia. Galactocerebrosidase dysfunction could also be a potential confounding factor for ABCA1 protein function.", "classifications": [ { "id": "Miyamoto", "label": "Group Miyamoto", "parent": "Wakamoto", "type": "group" }, { "id": "Wakamoto", "label": "Team Wakamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yasuhisa", "last_name": "Furuta", "name": null }, { "creator_type": "author", "first_name": "Yoshinori", "last_name": "Osaki", "name": null }, { "creator_type": "author", "first_name": "Yoshimi", "last_name": "Nakagawa", "name": null }, { "creator_type": "author", "first_name": "Song-Iee", "last_name": "Han", "name": null }, { "creator_type": "author", "first_name": "Masaya", "last_name": "Araki", "name": null }, { "creator_type": "author", "first_name": "Akito", "last_name": "Shikama", "name": null }, { "creator_type": "author", "first_name": "Nami", "last_name": "Ohuchi", "name": null }, { "creator_type": "author", "first_name": "Daichi", "last_name": "Yamazaki", "name": null }, { "creator_type": "author", "first_name": "Erika", "last_name": "Matsuda", "name": null }, { "creator_type": "author", "first_name": "Seitaro", "last_name": "Nohara", "name": null }, { "creator_type": "author", "first_name": "Yuhei", "last_name": "Mizunoe", "name": null }, { "creator_type": "author", "first_name": "Kenta", "last_name": "Kainoh", "name": null }, { "creator_type": "author", "first_name": "Yasuhito", "last_name": "Suehara", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Ohno", "name": null }, { "creator_type": "author", "first_name": "Yoshinori", "last_name": "Takeuchi", "name": null }, { "creator_type": "author", "first_name": "Takafumi", "last_name": "Miyamoto", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Murayama", "name": null }, { "creator_type": "author", "first_name": "Yoko", "last_name": "Sugano", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Iwasaki", "name": null }, { "creator_type": "author", "first_name": "Ken-Ichi", "last_name": "Hirano", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Koseki", "name": null }, { "creator_type": "author", "first_name": "Shogo", "last_name": "Nakano", "name": null }, { "creator_type": "author", "first_name": "Hiroaki", "last_name": "Tokiwa", "name": null }, { "creator_type": "author", "first_name": "Motohiro", "last_name": "Sekiya", "name": null }, { "creator_type": "author", "first_name": "Naoya", "last_name": "Yahagi", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Matsuzaka", "name": null }, { "creator_type": "author", "first_name": "Kiyotaka", "last_name": "Nakamagoe", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Tomidokoro", "name": null }, { "creator_type": "author", "first_name": "Jun", "last_name": "Mitsui", "name": null }, { "creator_type": "author", "first_name": "Shoji", "last_name": "Tsuji", "name": null }, { "creator_type": "author", "first_name": "Hiroaki", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Shimano", "name": null } ], "identifiers": { "doi": { "normalized": "10.5551/jat.64579" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "38538338" } }, "mesh": [ { "descriptor": "ATP Binding Cassette Transporter 1", "descriptor_ui": "D064286", "major_topic": true }, { "descriptor": "Cholesterol, HDL", "descriptor_ui": "D008076", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "HEK293 Cells", "descriptor_ui": "D057809", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": false }, { "descriptor": "Tangier Disease", "descriptor_ui": "D013631", "major_topic": false }, { "descriptor": "Young Adult", "descriptor_ui": "D055815", "major_topic": false } ], "publication": { "conference_name": null, "date": "2024 Mar 28", "date_precision": "day", "issue": "", "normalized_date": "2024-03-28", "pages": "", "proceedings_title": null, "publisher": "", "title": "Journal of atherosclerosis and thrombosis", "volume": "", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Genetic and Functional Analyses of Patients with Marked Hypo-High-Density Lipoprotein Cholesterolemia.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Tissues consist of cells with different molecular and/or mechanical properties. Measuring the forces and stresses in mixed-cell populations is essential for understanding the mechanisms by which tissue development, homeostasis, and disease emerge from the cooperation of distinct cell types. However, many previous studies have primarily focused their mechanical measurements on dissociated cells or aggregates of a single-cell type, leaving the mechanics of mixed-cell populations largely unexplored. In the present study, we aimed to elucidate the influence of interactions between different cell types on cell mechanics by conducting in situ mechanical measurements on a monolayer of mammalian epithelial cells. Our findings revealed that while individual cell types displayed varying magnitudes of traction and intercellular stress before mixing, these mechanical values shifted in the mixed monolayer, becoming nearly indistinguishable between the cell types. Moreover, by analyzing a mixed-phase model of active tissues, we identified physical conditions under which such mechanical convergence is induced. Overall, the present study underscores the importance of in situ mechanical measurements in mixed-cell populations to deepen our understanding of the mechanics of multicellular systems.", "classifications": [ { "id": "JPMJCR1923", "label": "JPMJCR1923", "researcher": "Satoshi Sawai", "type": "grant" }, { "id": "Ishihara", "label": "Group Ishihara", "parent": "Sawai", "type": "group" }, { "id": "Sawai", "label": "Group Sawai", "parent": "Sawai", "type": "group" }, { "id": "Sawai", "label": "Team Sawai", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Estelle", "last_name": "Gauquelin", "name": null }, { "creator_type": "author", "first_name": "Keisuke", "last_name": "Kuromiya", "name": null }, { "creator_type": "author", "first_name": "Toshinori", "last_name": "Namba", "name": null }, { "creator_type": "author", "first_name": "Keisuke", "last_name": "Ikawa", "name": null }, { "creator_type": "author", "first_name": "Yasuyuki", "last_name": "Fujita", "name": null }, { "creator_type": "author", "first_name": "Shuji", "last_name": "Ishihara", "name": null }, { "creator_type": "author", "first_name": "Kaoru", "last_name": "Sugimura", "name": null } ], "identifiers": { "doi": { "normalized": "10.1140/epje/s10189-024-00415-w" }, "pmcid": { "normalized": "PMC10973031" }, "pmid": { "normalized": "38538808" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Biomechanical Phenomena", "descriptor_ui": "D001696", "major_topic": false }, { "descriptor": "Epithelial Cells", "descriptor_ui": "D004847", "major_topic": true }, { "descriptor": "Mammals", "descriptor_ui": "D008322", "major_topic": true }, { "descriptor": "Stress, Mechanical", "descriptor_ui": "D013314", "major_topic": false } ], "publication": { "conference_name": null, "date": "2024 Mar 27", "date_precision": "day", "issue": "3", "normalized_date": "2024-03-27", "pages": "21", "proceedings_title": null, "publisher": "", "title": "The European physical journal. E, Soft matter", "volume": "47", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Mechanical convergence in mixed populations of mammalian epithelial cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Overcoming resistance to immune checkpoint inhibitors is an important issue in patients with non-small-cell lung cancer (NSCLC). Transcriptome analysis shows that adenocarcinoma can be divided into three molecular subtypes: terminal respiratory unit (TRU), proximal proliferative (PP), and proximal inflammatory (PI), and squamous cell carcinoma (LUSQ) into four. However, the immunological characteristics of these subtypes are not fully understood. In this study, we investigated the immune landscape of NSCLC tissues in molecular subtypes using a multi-omics dataset, including tumor-infiltrating leukocytes (TILs) analyzed using flow cytometry, RNA sequences, whole exome sequences, metabolomic analysis, and clinicopathologic findings. In the PI subtype, the number of TILs increased and the immune response in the tumor microenvironment (TME) was activated, as indicated by high levels of tertiary lymphoid structures, and high cytotoxic marker levels. Patient prognosis was worse in the PP subtype than in other adenocarcinoma subtypes. Glucose transporter 1 (GLUT1) expression levels were upregulated and lactate accumulated in the TME of the PP subtype. This could lead to the formation of an immunosuppressive TME, including the inactivation of antigen-presenting cells. The TRU subtype had low biological malignancy and \"cold\" tumor-immune phenotypes. Squamous cell carcinoma (LUSQ) did not show distinct immunological characteristics in its respective subtypes. Elucidation of the immune characteristics of molecular subtypes could lead to the development of personalized immune therapy for lung cancer. Immune checkpoint inhibitors could be an effective treatment for the PI subtype. Glycolysis is a potential target for converting an immunosuppressive TME into an antitumorigenic TME in the PP subtype.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Hironori", "last_name": "Fukuda", "name": null }, { "creator_type": "author", "first_name": "Kosuke", "last_name": "Arai", "name": null }, { "creator_type": "author", "first_name": "Hideaki", "last_name": "Mizuno", "name": null }, { "creator_type": "author", "first_name": "Yukari", "last_name": "Nishito", "name": null }, { "creator_type": "author", "first_name": "Noriko", "last_name": "Motoi", "name": null }, { "creator_type": "author", "first_name": "Yasuhito", "last_name": "Arai", "name": null }, { "creator_type": "author", "first_name": "Nobuyoshi", "last_name": "Hiraoka", "name": null }, { "creator_type": "author", "first_name": "Tatsuhiro", "last_name": "Shibata", "name": null }, { "creator_type": "author", "first_name": "Yukiko", "last_name": "Sonobe", "name": null }, { "creator_type": "author", "first_name": "Yoko", "last_name": "Kayukawa", "name": null }, { "creator_type": "author", "first_name": "Eri", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Mina", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Etsuko", "last_name": "Fujii", "name": null }, { "creator_type": "author", "first_name": "Toru", "last_name": "Maruyama", "name": null }, { "creator_type": "author", "first_name": "Kenta", "last_name": "Kuwabara", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Nishizawa", "name": null }, { "creator_type": "author", "first_name": "Yukihiro", "last_name": "Mizoguchi", "name": null }, { "creator_type": "author", "first_name": "Yukihiro", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Shun-Ichi", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Makiko", "last_name": "Yamashita", "name": null }, { "creator_type": "author", "first_name": "Shigehisa", "last_name": "Kitano", "name": null }, { "creator_type": "author", "first_name": "Hiromi", "last_name": "Sakamoto", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Nagata", "name": null }, { "creator_type": "author", "first_name": "Risa", "last_name": "Mitsumori", "name": null }, { "creator_type": "author", "first_name": "Kouichi", "last_name": "Ozaki", "name": null }, { "creator_type": "author", "first_name": "Shumpei", "last_name": "Niida", "name": null }, { "creator_type": "author", "first_name": "Yae", "last_name": "Kanai", "name": null }, { "creator_type": "author", "first_name": "Akiyoshi", "last_name": "Hirayama", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Keisuke", "last_name": "Tsukada", "name": null }, { "creator_type": "author", "first_name": "Nami", "last_name": "Yabuki", "name": null }, { "creator_type": "author", "first_name": "Mei", "last_name": "Shimada", "name": null }, { "creator_type": "author", "first_name": "Takehisa", "last_name": "Kitazawa", "name": null }, { "creator_type": "author", "first_name": "Osamu", "last_name": "Natori", "name": null }, { "creator_type": "author", "first_name": "Noriaki", "last_name": "Sawada", "name": null }, { "creator_type": "author", "first_name": "Atsuhiko", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Teruhiko", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Kazuki", "last_name": "Yasuda", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Ochiai", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Tsunoda", "name": null }, { "creator_type": "author", "first_name": "Kazunori", "last_name": "Aoki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/cas.16154" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "38527308" } }, "mesh": [ { "descriptor": "Adenocarcinoma of Lung", "descriptor_ui": "D000077192", "major_topic": true }, { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Carcinoma, Non-Small-Cell Lung", "descriptor_ui": "D002289", "major_topic": false }, { "descriptor": "Carcinoma, Squamous Cell", "descriptor_ui": "D002294", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Gene Expression Profiling", "descriptor_ui": "D020869", "major_topic": false }, { "descriptor": "Gene Expression Regulation, Neoplastic", "descriptor_ui": "D015972", "major_topic": false }, { "descriptor": "Glucose Transporter Type 1", "descriptor_ui": "D051272", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Lung Neoplasms", "descriptor_ui": "D008175", "major_topic": true }, { "descriptor": "Lymphocytes, Tumor-Infiltrating", "descriptor_ui": "D016246", "major_topic": true }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Prognosis", "descriptor_ui": "D011379", "major_topic": false }, { "descriptor": "Tumor Microenvironment", "descriptor_ui": "D059016", "major_topic": true } ], "publication": { "conference_name": null, "date": "2024 Mar 25", "date_precision": "day", "issue": "", "normalized_date": "2024-03-25", "pages": "", "proceedings_title": null, "publisher": "", "title": "Cancer science", "volume": "", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Molecular subtypes of lung adenocarcinoma present distinct immune tumor microenvironments.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "We recently achieved the first-in-human transfusion of induced pluripotent stem cell-derived platelets (iPSC-PLTs) as an alternative to standard transfusions, which are dependent on donors and therefore variable in supply. However, heterogeneity characterized by thrombopoiesis-biased or immune-biased megakaryocytes (MKs) continues to pose a bottleneck against the standardization of iPSC-PLT manufacturing. To address this problem, here we employ microRNA (miRNA) switch biotechnology to distinguish subpopulations of imMKCLs, the MK cell lines producing iPSC-PLTs. Upon miRNA switch-based screening, we find imMKCLs with lower let-7 activity exhibit an immune-skewed transcriptional signature. Notably, the low activity of let-7a-5p results in the upregulation of RAS like proto-oncogene B (RALB) expression, which is crucial for the lineage determination of immune-biased imMKCL subpopulations and leads to the activation of interferon-dependent signaling. The dysregulation of immune properties/subpopulations, along with the secretion of inflammatory cytokines, contributes to a decline in the quality of the whole imMKCL population.", "classifications": [ { "id": "Yamamoto", "label": "Group Yamamoto", "parent": "Toyoshima", "type": "group" }, { "id": "Toyoshima", "label": "Team Toyoshima", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Si Jing", "last_name": "Chen", "name": null }, { "creator_type": "author", "first_name": "Kazuya", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Kosuke", "last_name": "Fujio", "name": null }, { "creator_type": "author", "first_name": "Karin", "last_name": "Hayashi", "name": null }, { "creator_type": "author", "first_name": "Sudip Kumar", "last_name": "Paul", "name": null }, { "creator_type": "author", "first_name": "Akinori", "last_name": "Yuzuriha", "name": null }, { "creator_type": "author", "first_name": "Wei-Yin", "last_name": "Qiu", "name": null }, { "creator_type": "author", "first_name": "Emiri", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Maria Alejandra", "last_name": "Kanashiro", "name": null }, { "creator_type": "author", "first_name": "Mio", "last_name": "Kabata", "name": null }, { "creator_type": "author", "first_name": "Sou", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Naoshi", "last_name": "Sugimoto", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Kaneda", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Hirohide", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Naoya", "last_name": "Takayama", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Eto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41467-024-46605-0" }, "pmcid": { "normalized": "PMC10960040" }, "pmid": { "normalized": "38519457" } }, "mesh": [ { "descriptor": "Blood Platelets", "descriptor_ui": "D001792", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Induced Pluripotent Stem Cells", "descriptor_ui": "D057026", "major_topic": true }, { "descriptor": "Megakaryocytes", "descriptor_ui": "D008533", "major_topic": false }, { "descriptor": "MicroRNAs", "descriptor_ui": "D035683", "major_topic": true }, { "descriptor": "Thrombopoiesis", "descriptor_ui": "D034061", "major_topic": false } ], "publication": { "conference_name": null, "date": "2024 Mar 22", "date_precision": "day", "issue": "1", "normalized_date": "2024-03-22", "pages": "2588", "proceedings_title": null, "publisher": "", "title": "Nature communications", "volume": "15", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "A let-7 microRNA-RALB axis links the immune properties of iPSC-derived megakaryocytes with platelet producibility.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "cAMP is a universal second messenger regulated by various upstream pathways including Ca(2+) and G-protein-coupled receptors (GPCRs). To decipher in vivo cAMP dynamics, we rationally designed cAMPinG1, a sensitive genetically encoded green cAMP indicator that outperformed its predecessors in both dynamic range and cAMP affinity. Two-photon cAMPinG1 imaging detected cAMP transients in the somata and dendritic spines of neurons in the mouse visual cortex on the order of tens of seconds. In addition, multicolor imaging with a sensitive red Ca(2+) indicator RCaMP3 allowed simultaneous measurement of population patterns in Ca(2+) and cAMP in hundreds of neurons. We found Ca(2+)-related cAMP responses that represented specific information, such as direction selectivity in vision and locomotion, as well as GPCR-related cAMP responses. Overall, our multicolor suite will facilitate analysis of the interaction between the Ca(2+), GPCR and cAMP signaling at single-cell resolution both in vitro and in vivo.", "classifications": [ { "id": "JPMJCR1921", "label": "JPMJCR1921", "researcher": "Itaru Imayoshi", "type": "grant" }, { "id": "Imayoshi", "label": "Group Imayoshi", "parent": "Imayoshi", "type": "group" }, { "id": "Imayoshi", "label": "Team Imayoshi", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Tatsushi", "last_name": "Yokoyama", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Manita", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Uwamori", "name": null }, { "creator_type": "author", "first_name": "Mio", "last_name": "Tajiri", "name": null }, { "creator_type": "author", "first_name": "Itaru", "last_name": "Imayoshi", "name": null }, { "creator_type": "author", "first_name": "Sho", "last_name": "Yagishita", "name": null }, { "creator_type": "author", "first_name": "Masanori", "last_name": "Murayama", "name": null }, { "creator_type": "author", "first_name": "Kazuo", "last_name": "Kitamura", "name": null }, { "creator_type": "author", "first_name": "Masayuki", "last_name": "Sakamoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41592-024-02222-9" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "38514778" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Calcium", "descriptor_ui": "D002118", "major_topic": true }, { "descriptor": "Calcium Signaling", "descriptor_ui": "D020013", "major_topic": false }, { "descriptor": "Cyclic AMP", "descriptor_ui": "D000242", "major_topic": true }, { "descriptor": "HEK293 Cells", "descriptor_ui": "D057809", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": true }, { "descriptor": "Receptors, G-Protein-Coupled", "descriptor_ui": "D043562", "major_topic": false }, { "descriptor": "Visual Cortex", "descriptor_ui": "D014793", "major_topic": true } ], "publication": { "conference_name": null, "date": "2024 Mar 21", "date_precision": "day", "issue": "", "normalized_date": "2024-03-21", "pages": "", "proceedings_title": null, "publisher": "", "title": "Nature methods", "volume": "", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "A multicolor suite for deciphering population coding of calcium and cAMP in vivo.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "We introduce a simple integrated analysis method that links cellular phenotypic behaviour with single-cell RNA sequencing (scRNA-seq) by utilizing a combination of optical indices from cells and hydrogel beads. With our method, the combinations, referred to as joint colour codes, enable the link via matching the optical combinations measured by conventional epi-fluorescence microscopy with the concatenated DNA molecular barcodes created by cell-hydrogel bead pairs and sequenced by next-generation sequencing. We validated our approach by demonstrating an accurate link between the cell image and scRNA-seq with mixed species experiments, longitudinal cell tagging by electroporation and lipofection, and gene expression analysis. Furthermore, we extended our approach to multiplexed chemical transcriptomics, which enabled us to identify distinct phenotypic behaviours in HeLa cells treated with various concentrations of paclitaxel, and determine the corresponding gene regulation associated with the formation of a multipolar spindle.", "classifications": [ { "id": "Shintaku", "label": "Group Shintaku", "parent": "Shintaku", "type": "group" }, { "id": "Shintaku", "label": "Team Shintaku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Arata", "last_name": "Tsuchida", "name": null }, { "creator_type": "author", "first_name": "Taikopaul", "last_name": "Kaneko", "name": null }, { "creator_type": "author", "first_name": "Kaori", "last_name": "Nishikawa", "name": null }, { "creator_type": "author", "first_name": "Mayu", "last_name": "Kawasaki", "name": null }, { "creator_type": "author", "first_name": "Ryuji", "last_name": "Yokokawa", "name": null }, { "creator_type": "author", "first_name": "Hirofumi", "last_name": "Shintaku", "name": null } ], "identifiers": { "doi": { "normalized": "10.1039/d3lc00866e" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "38506394" } }, "mesh": [ { "descriptor": "Gene Expression Profiling", "descriptor_ui": "D020869", "major_topic": true }, { "descriptor": "HeLa Cells", "descriptor_ui": "D006367", "major_topic": false }, { "descriptor": "High-Throughput Nucleotide Sequencing", "descriptor_ui": "D059014", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Hydrogels", "descriptor_ui": "D020100", "major_topic": false }, { "descriptor": "Sequence Analysis, RNA", "descriptor_ui": "D017423", "major_topic": false }, { "descriptor": "Single-Cell Analysis", "descriptor_ui": "D059010", "major_topic": false }, { "descriptor": "Transcriptome", "descriptor_ui": "D059467", "major_topic": true } ], "publication": { "conference_name": null, "date": "2024 Mar 20", "date_precision": "day", "issue": "", "normalized_date": "2024-03-20", "pages": "", "proceedings_title": null, "publisher": "", "title": "Lab on a chip", "volume": "", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Opto-combinatorial indexing enables high-content transcriptomics by linking cell images and transcriptomes.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Capturing images of the nuclear dynamics within live cells is an essential technique for comprehending the intricate biological processes inherent to plant cell nuclei. While various methods exist for imaging nuclei, including combining fluorescent proteins and dyes with microscopy, there is a dearth of commercially available dyes for live-cell imaging. In Arabidopsis thaliana, we discovered that nuclei emit autofluorescence in the near-infrared (NIR) range of the spectrum and devised a non-invasive technique for the visualization of live cell nuclei using this inherent NIR autofluorescence. Our studies demonstrated the capability of the NIR imaging technique to visualize the dynamic behavior of nuclei within primary roots, root hairs, and pollen tubes, which are tissues that harbor a limited number of other organelles displaying autofluorescence. We further demonstrated the applicability of NIR autofluorescence imaging in various other tissues by incorporating fluorescence lifetime imaging techniques. Nuclear autofluorescence was also detected across a wide range of plant species, enabling analyses without the need for transformation. The nuclear autofluorescence in the NIR wavelength range was not observed in animal or yeast cells. Genetic analysis revealed that this autofluorescence was caused by the phytochrome protein. Our studies demonstrated that nuclear autofluorescence imaging can be effectively employed not only in model plants but also for studying nuclei in non-model plant species.", "classifications": [ { "id": "Sato", "label": "Group Sato", "parent": "Tsuchiya", "type": "group" }, { "id": "Tsuchiya", "label": "Team Tsuchiya", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Akira", "last_name": "Yoshinari", "name": null }, { "creator_type": "author", "first_name": "Reika", "last_name": "Isoda", "name": null }, { "creator_type": "author", "first_name": "Noriyoshi", "last_name": "Yagi", "name": null }, { "creator_type": "author", "first_name": "Yoshikatsu", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Jelmer J.", "last_name": "Lindeboom", "name": null }, { "creator_type": "author", "first_name": "David W.", "last_name": "Ehrhardt", "name": null }, { "creator_type": "author", "first_name": "Wolf B.", "last_name": "Frommer", "name": null }, { "creator_type": "author", "first_name": "Masayoshi", "last_name": "Nakamura", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/tpj.16699" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "38509728" } }, "mesh": [ { "descriptor": "Arabidopsis", "descriptor_ui": "D017360", "major_topic": true }, { "descriptor": "Arabidopsis Proteins", "descriptor_ui": "D029681", "major_topic": false }, { "descriptor": "Cell Nucleus", "descriptor_ui": "D002467", "major_topic": true }, { "descriptor": "Fluorescence", "descriptor_ui": "D005453", "major_topic": false }, { "descriptor": "Optical Imaging", "descriptor_ui": "D061848", "major_topic": true }, { "descriptor": "Phytochrome", "descriptor_ui": "D010834", "major_topic": false }, { "descriptor": "Plant Roots", "descriptor_ui": "D018517", "major_topic": false } ], "publication": { "conference_name": null, "date": "2024 Mar 20", "date_precision": "day", "issue": "", "normalized_date": "2024-03-20", "pages": "", "proceedings_title": null, "publisher": "", "title": "The Plant journal : for cell and molecular biology", "volume": "", "year": 2024 }, "ssbd": { "database": [ "ssbd-database-000474" ], "repository": [ "ssbd-repos-000474" ] }, "title": "Near-infrared imaging of phytochrome-derived autofluorescence in plant nuclei.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Morphological and structural remodeling of the heart, including cardiac hypertrophy and fibrosis, has been considered a therapeutic target for heart failure for approximately three decades. Groundbreaking heart failure medications demonstrating reverse remodeling effects have contributed significantly to medical advancements. However, nearly 50% of heart failure patients still exhibit drug resistance, posing a challenge to the healthcare system. Recently, characteristics of heart failure resistant to ARBs and beta-blockers have been defined, highlighting preserved systolic function despite impaired diastolic function, leading to the classification of heart failure with preserved ejection fraction (HFpEF). The pathogenesis and etiology of HFpEF may be related to metabolic abnormalities, as evidenced by its mimicry through endothelial dysfunction and excessive intake of high-fat diets. Our recent findings indicate a significant involvement of mitochondrial hyper-fission in the progression of heart failure. This mitochondrial pathological remodeling is associated with redox imbalance, especially hydrogen sulfide accumulation due to abnormal electron leak in myocardium. In this review, we also introduce a novel therapeutic strategy for heart failure from the current perspective of mitochondrial redox-metabolic remodeling.", "classifications": [ { "id": "Nishida", "label": "Group Nishida", "parent": "Nishida", "type": "group" }, { "id": "Nishimura", "label": "Group Nishimura", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Motohiro", "last_name": "Nishida", "name": null }, { "creator_type": "author", "first_name": "Xinya", "last_name": "Mi", "name": null }, { "creator_type": "author", "first_name": "Yukina", "last_name": "Ishii", "name": null }, { "creator_type": "author", "first_name": "Yuri", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Akiyuki", "last_name": "Nishimura", "name": null } ], "identifiers": { "doi": { "normalized": "10.1093/jb/mvae031" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "38507681" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Heart Failure", "descriptor_ui": "D006333", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mitochondria, Heart", "descriptor_ui": "D008929", "major_topic": false }, { "descriptor": "Myocardium", "descriptor_ui": "D009206", "major_topic": false }, { "descriptor": "Ventricular Remodeling", "descriptor_ui": "D020257", "major_topic": true } ], "publication": { "conference_name": null, "date": "2024 Mar 20", "date_precision": "day", "issue": "", "normalized_date": "2024-03-20", "pages": "mvae031", "proceedings_title": null, "publisher": "", "title": "Journal of biochemistry", "volume": "", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Cardiac Remodeling: Novel Pathophysiological Mechanisms and Therapeutic Strategies.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Accelerating the measurement for discrimination of samples, such as classification of cell phenotype, is crucial when faced with significant time and cost constraints. Spontaneous Raman microscopy offers label-free, rich chemical information but suffers from long acquisition time due to extremely small scattering cross-sections. One possible approach to accelerate the measurement is by measuring necessary parts with a suitable number of illumination points. However, how to design these points during measurement remains a challenge. To address this, we developed an imaging technique based on a reinforcement learning in machine learning (ML). This ML approach adaptively feeds back \"optimal\" illumination pattern during the measurement to detect the existence of specific characteristics of interest, allowing faster measurements while guaranteeing discrimination accuracy. Using a set of Raman images of human follicular thyroid and follicular thyroid carcinoma cells, we showed that our technique requires 3,333 to 31,683 times smaller number of illuminations for discriminating the phenotypes than raster scanning. To quantitatively evaluate the number of illuminations depending on the requisite discrimination accuracy, we prepared a set of polymer bead mixture samples to model anomalous and normal tissues. We then applied a home-built programmable-illumination microscope equipped with our algorithm, and confirmed that the system can discriminate the sample conditions with 104 to 4,350 times smaller number of illuminations compared to standard point illumination Raman microscopy. The proposed algorithm can be applied to other types of microscopy that can control measurement condition on the fly, offering an approach for the acceleration of accurate measurements in various applications including medical diagnosis.", "classifications": [ { "id": "Fujita", "label": "Group Fujita", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Koji", "last_name": "Tabata", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Kawagoe", "name": null }, { "creator_type": "author", "first_name": "J. Nicholas", "last_name": "Taylor", "name": null }, { "creator_type": "author", "first_name": "Kentaro", "last_name": "Mochizuki", "name": null }, { "creator_type": "author", "first_name": "Toshiki", "last_name": "Kubo", "name": null }, { "creator_type": "author", "first_name": "Jean-Emmanuel", "last_name": "Clement", "name": null }, { "creator_type": "author", "first_name": "Yasuaki", "last_name": "Kumamoto", "name": null }, { "creator_type": "author", "first_name": "Yoshinori", "last_name": "Harada", "name": null }, { "creator_type": "author", "first_name": "Atsuyoshi", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Katsumasa", "last_name": "Fujita", "name": null }, { "creator_type": "author", "first_name": "Tamiki", "last_name": "Komatsuzaki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1073/pnas.2304866121" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "38483992" } }, "mesh": [ { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Machine Learning", "descriptor_ui": "D000069550", "major_topic": false }, { "descriptor": "Microscopy", "descriptor_ui": "D008853", "major_topic": true }, { "descriptor": "Nonlinear Optical Microscopy", "descriptor_ui": "D000073758", "major_topic": false }, { "descriptor": "Spectrum Analysis, Raman", "descriptor_ui": "D013059", "major_topic": true }, { "descriptor": "Thyroid Gland", "descriptor_ui": "D013961", "major_topic": false } ], "publication": { "conference_name": null, "date": "2024 Mar 19", "date_precision": "day", "issue": "12", "normalized_date": "2024-03-19", "pages": "e2304866121", "proceedings_title": null, "publisher": "", "title": "Proceedings of the National Academy of Sciences of the United States of America", "volume": "121", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "On-the-fly Raman microscopy guaranteeing the accuracy of discrimination.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "HPLC-MS analysis revealed the presence of an unreported peptide in the extract of the marine sponge Neopetrosia sp. Its structure was determined as a tripeptide, named neopetromin (1), composed of two tyrosine and one tryptophan residues with a heteroaromatic C-N cross-link between side chains. The absolute configuration of amino acids was determined using Marfey's method after ozonolysis and hydrolysis of 1. Compound 1 promoted vacuole fragmentation in an actin-independent manner in tobacco BY-2 cells.", "classifications": [ { "id": "Higaki", "label": "Group Higaki", "parent": "Ueda", "type": "group" }, { "id": "Ueda", "label": "Team Ueda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yuki", "last_name": "Hitora", "name": null }, { "creator_type": "author", "first_name": "Ahmed H.", "last_name": "El-Desoky", "name": null }, { "creator_type": "author", "first_name": "Yusaku", "last_name": "Sadahiro", "name": null }, { "creator_type": "author", "first_name": "Ai", "last_name": "Sejiyama", "name": null }, { "creator_type": "author", "first_name": "Amiri", "last_name": "Kinoshita", "name": null }, { "creator_type": "author", "first_name": "Yuji", "last_name": "Ise", "name": null }, { "creator_type": "author", "first_name": "Esther D.", "last_name": "Angkouw", "name": null }, { "creator_type": "author", "first_name": "Remy E. P.", "last_name": "Mangindaan", "name": null }, { "creator_type": "author", "first_name": "Takumi", "last_name": "Higaki", "name": null }, { "creator_type": "author", "first_name": "Sachiko", "last_name": "Tsukamoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/acs.jnatprod.4c00158" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "38503712" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Chromatography, High Pressure Liquid", "descriptor_ui": "D002851", "major_topic": false }, { "descriptor": "Marine Biology", "descriptor_ui": "D008386", "major_topic": false }, { "descriptor": "Molecular Structure", "descriptor_ui": "D015394", "major_topic": false }, { "descriptor": "Nicotiana", "descriptor_ui": "D014026", "major_topic": true }, { "descriptor": "Oligopeptides", "descriptor_ui": "D009842", "major_topic": false }, { "descriptor": "Peptides, Cyclic", "descriptor_ui": "D010456", "major_topic": false }, { "descriptor": "Porifera", "descriptor_ui": "D011161", "major_topic": true }, { "descriptor": "Tryptophan", "descriptor_ui": "D014364", "major_topic": false }, { "descriptor": "Vacuoles", "descriptor_ui": "D014617", "major_topic": true } ], "publication": { "conference_name": null, "date": "2024 Mar 19", "date_precision": "day", "issue": "", "normalized_date": "2024-03-19", "pages": "", "proceedings_title": null, "publisher": "", "title": "Journal of natural products", "volume": "", "year": 2024 }, "ssbd": { "database": [ "ssbd-database-000451" ], "repository": [ "ssbd-repos-000451" ] }, "title": "Neopetromin, a Cyclic Tripeptide with a C-N Cross-Link, from the Marine Sponge Neopetrosia sp., That Causes Vacuole Fragmentation in Tobacco BY-2 Cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Reactive sulfane sulfur species such as persulfides (RSSH) and H(2)S(2) are important redox regulators and closely linked to H(2)S signaling. However, the study of these species is still challenging due to their instability, high reactivity, and the lack of suitable donors to produce them. Herein we report a unique compound, 2H-thiopyran-2-thione sulfine (TTS), which can specifically convert H(2)S to HSOH, and then to H(2)S(2) in the presence of excess H(2)S. Meanwhile, the reaction product 2H-thiopyran-2-thione (TT) can be oxidized to reform TTS by biological oxidants. The reaction mechanism of TTS is studied experimentally and computationally. TTS can be conjugated to proteins to achieve specific delivery, and the combination of TTS and H(2)S leads to highly efficient protein persulfidation. When TTS is applied in conjunction with established H(2)S donors, the corresponding donors of H(2)S(2) (or its equivalents) are obtained. Cell-based studies reveal that TTS can effectively increase intracellular sulfane sulfur levels and compensate for certain aspects of sulfide:quinone oxidoreductase (SQR) deficiency. These properties make TTS a conceptually new strategy for the design of donors of reactive sulfane sulfur species.", "classifications": [ { "id": "JPMJCR2024", "label": "JPMJCR2024", "researcher": "Motohiro Nishida", "type": "grant" }, { "id": "Akaike", "label": "Group Akaike", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Group Nishida", "parent": "Nishida", "type": "group" }, { "id": "Nishimura", "label": "Group Nishimura", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Qi", "last_name": "Cui", "name": null }, { "creator_type": "author", "first_name": "Meg", "last_name": "Shieh", "name": null }, { "creator_type": "author", "first_name": "Tony W.", "last_name": "Pan", "name": null }, { "creator_type": "author", "first_name": "Akiyuki", "last_name": "Nishimura", "name": null }, { "creator_type": "author", "first_name": "Tetsuro", "last_name": "Matsunaga", "name": null }, { "creator_type": "author", "first_name": "Shane S.", "last_name": "Kelly", "name": null }, { "creator_type": "author", "first_name": "Shi", "last_name": "Xu", "name": null }, { "creator_type": "author", "first_name": "Minkyung", "last_name": "Jung", "name": null }, { "creator_type": "author", "first_name": "Seiryo", "last_name": "Ogata", "name": null }, { "creator_type": "author", "first_name": "Masanobu", "last_name": "Morita", "name": null }, { "creator_type": "author", "first_name": "Jun", "last_name": "Yoshitake", "name": null }, { "creator_type": "author", "first_name": "Xiaoyan", "last_name": "Chen", "name": null }, { "creator_type": "author", "first_name": "Jerome R.", "last_name": "Robinson", "name": null }, { "creator_type": "author", "first_name": "Wei-Jun", "last_name": "Qian", "name": null }, { "creator_type": "author", "first_name": "Motohiro", "last_name": "Nishida", "name": null }, { "creator_type": "author", "first_name": "Takaaki", "last_name": "Akaike", "name": null }, { "creator_type": "author", "first_name": "Ming", "last_name": "Xian", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41467-024-46652-7" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "38503758" } }, "mesh": [ { "descriptor": "Hydrogen Sulfide", "descriptor_ui": "D006862", "major_topic": true }, { "descriptor": "Oxidation-Reduction", "descriptor_ui": "D010084", "major_topic": false }, { "descriptor": "Proteins", "descriptor_ui": "D011506", "major_topic": false }, { "descriptor": "Pyrans", "descriptor_ui": "D011714", "major_topic": true }, { "descriptor": "Sulfhydryl Compounds", "descriptor_ui": "D013438", "major_topic": true }, { "descriptor": "Sulfides", "descriptor_ui": "D013440", "major_topic": false }, { "descriptor": "Sulfur", "descriptor_ui": "D013455", "major_topic": false }, { "descriptor": "Thiones", "descriptor_ui": "D013871", "major_topic": false } ], "publication": { "conference_name": null, "date": "2024 Mar 19", "date_precision": "day", "issue": "1", "normalized_date": "2024-03-19", "pages": "2453", "proceedings_title": null, "publisher": "", "title": "Nature communications", "volume": "15", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "2H-Thiopyran-2-thione sulfine, a compound for converting H(2)S to HSOH/H(2)S(2) and increasing intracellular sulfane sulfur levels.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Dysregulation of liver metabolism associated with obesity during feeding and fasting leads to the breakdown of metabolic homeostasis. However, the underlying mechanism remains unknown. Here, we measured multi-omics data in the liver of wild-type and leptin-deficient obese (ob/ob) mice at ad libitum feeding and constructed a differential regulatory trans-omic network of metabolic reactions. We compared the trans-omic network at feeding with that at 16 h fasting constructed in our previous study. Intermediate metabolites in glycolytic and nucleotide metabolism decreased in ob/ob mice at feeding but increased at fasting. Allosteric regulation reversely shifted between feeding and fasting, generally showing activation at feeding while inhibition at fasting in ob/ob mice. Transcriptional regulation was similar between feeding and fasting, generally showing inhibiting transcription factor regulations and activating enzyme protein regulations in ob/ob mice. The opposite metabolic dysregulation between feeding and fasting characterizes breakdown of metabolic homeostasis associated with obesity.", "classifications": [ { "id": "JPMJCR2123", "label": "JPMJCR2123", "researcher": "Shinya Kuroda", "type": "grant" }, { "id": "Inaba", "label": "Group Inaba", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Group Kuroda", "parent": "Kuroda", "type": "group" }, { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yunfan", "last_name": "Bai", "name": null }, { "creator_type": "author", "first_name": "Keigo", "last_name": "Morita", "name": null }, { "creator_type": "author", "first_name": "Toshiya", "last_name": "Kokaji", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Hatano", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Ohno", "name": null }, { "creator_type": "author", "first_name": "Riku", "last_name": "Egami", "name": null }, { "creator_type": "author", "first_name": "Yifei", "last_name": "Pan", "name": null }, { "creator_type": "author", "first_name": "Dongzi", "last_name": "Li", "name": null }, { "creator_type": "author", "first_name": "Katsuyuki", "last_name": "Yugi", "name": null }, { "creator_type": "author", "first_name": "Saori", "last_name": "Uematsu", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Inoue", "name": null }, { "creator_type": "author", "first_name": "Yuka", "last_name": "Inaba", "name": null }, { "creator_type": "author", "first_name": "Yutaka", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Masaki", "last_name": "Matsumoto", "name": null }, { "creator_type": "author", "first_name": "Masatomo", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Yoshihiro", "last_name": "Izumi", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Bamba", "name": null }, { "creator_type": "author", "first_name": "Akiyoshi", "last_name": "Hirayama", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Kuroda", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.isci.2024.109121" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "38524370" } }, "mesh": [], "publication": { "conference_name": null, "date": "2024 Mar 15", "date_precision": "day", "issue": "3", "normalized_date": "2024-03-15", "pages": "", "proceedings_title": null, "publisher": "", "title": "iScience", "volume": "27", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Trans-omic analysis reveals opposite metabolic dysregulation between feeding and fasting in liver associated with obesity.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Human pluripotent stem cells (hPSCs) dynamically respond to their chemical and physical microenvironment, dictating their behavior. However, conventional in vitro studies predominantly employ plastic culture wares, which offer a simplified representation of the in vivo microenvironment. Emerging evidence underscores the pivotal role of mechanical and topological cues in hPSC differentiation and maintenance. In this study, we cultured hPSCs on hydrogel substrates with spatially controlled stiffness. The use of culture substrates that enable precise manipulation of spatial mechanical properties holds promise for better mimicking in vivo conditions and advancing tissue engineering techniques. We designed a photocurable polyethylene glycol-polyvinyl alcohol (PVA-PEG) hydrogel, allowing the spatial control of surface stiffness and geometry at a micrometer scale. This versatile hydrogel can be functionalized with various extracellular matrix proteins. Laminin 511-functionalized PVA-PEG gel effectively supports the growth and differentiation of hPSCs. Moreover, by spatially modulating the stiffness of the patterned gel, we achieved spatially selective cell differentiation, resulting in the generation of intricate patterned structures.", "classifications": [ { "id": "Eiraku", "label": "Group Eiraku", "parent": "Eiraku", "type": "group" }, { "id": "Maki", "label": "Group Maki", "parent": "Toyoshima", "type": "group" }, { "id": "Eiraku", "label": "Team Eiraku", "type": "team" }, { "id": "Toyoshima", "label": "Team Toyoshima", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Zhe", "last_name": "Wang", "name": null }, { "creator_type": "author", "first_name": "Akira", "last_name": "Numada", "name": null }, { "creator_type": "author", "first_name": "Fumi", "last_name": "Wagai", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Oda", "name": null }, { "creator_type": "author", "first_name": "Masatoshi", "last_name": "Ohgushi", "name": null }, { "creator_type": "author", "first_name": "Koichiro", "last_name": "Maki", "name": null }, { "creator_type": "author", "first_name": "Taiji", "last_name": "Adachi", "name": null }, { "creator_type": "author", "first_name": "Mototsugu", "last_name": "Eiraku", "name": null } ], "identifiers": { "doi": { "normalized": "10.1242/dev.201621" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "38512805" } }, "mesh": [ { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Hydrogels", "descriptor_ui": "D020100", "major_topic": true }, { "descriptor": "Pluripotent Stem Cells", "descriptor_ui": "D039904", "major_topic": true }, { "descriptor": "Tissue Engineering", "descriptor_ui": "D023822", "major_topic": false } ], "publication": { "conference_name": null, "date": "2024 Mar 15", "date_precision": "day", "issue": "6", "normalized_date": "2024-03-15", "pages": "dev201621", "proceedings_title": null, "publisher": "", "title": "Development (Cambridge, England)", "volume": "151", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Spatial cell fate manipulation of human pluripotent stem cells by controlling the microenvironment using photocurable hydrogel.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The emergence of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) variants necessitated a rapid evaluation system for their pathogenesis. Lung epithelial cells are their entry points; however, in addition to their limited source, the culture of human alveolar epithelial cells is especially complicated. Induced pluripotent stem cells (iPSCs) are an alternative source of human primary stem cells. Here, we report a model for distinguishing SARS-CoV-2 variants at high resolution, using separately induced iPSC-derived alveolar and airway cells in micro-patterned culture plates. The position-specific signals induced the apical-out alveolar type 2 and multiciliated airway cells at the periphery and center of the colonies, respectively. The infection studies in each lineage enabled profiling of the pathogenesis of SARS-CoV-2 variants: infection efficiency, tropism to alveolar and airway lineages, and their responses. These results indicate that this culture system is suitable for predicting the pathogenesis of emergent SARS-CoV-2 variants.", "classifications": [ { "id": "Yamamoto", "label": "Group Yamamoto", "parent": "Toyoshima", "type": "group" }, { "id": "Toyoshima", "label": "Team Toyoshima", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Atsushi", "last_name": "Masui", "name": null }, { "creator_type": "author", "first_name": "Rina", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Yasufumi", "last_name": "Matsumura", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Miki", "last_name": "Nagao", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Noda", "name": null }, { "creator_type": "author", "first_name": "Kazuo", "last_name": "Takayama", "name": null }, { "creator_type": "author", "first_name": "Shimpei", "last_name": "Gotoh", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.stemcr.2024.02.011" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "38552631" } }, "mesh": [ { "descriptor": "COVID-19", "descriptor_ui": "D000086382", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Induced Pluripotent Stem Cells", "descriptor_ui": "D057026", "major_topic": true }, { "descriptor": "Lung", "descriptor_ui": "D008168", "major_topic": false }, { "descriptor": "SARS-CoV-2", "descriptor_ui": "D000086402", "major_topic": false } ], "publication": { "conference_name": null, "date": "2024 Mar 15", "date_precision": "day", "issue": "", "normalized_date": "2024-03-15", "pages": "S2213-6711(24)00048-1", "proceedings_title": null, "publisher": "", "title": "Stem cell reports", "volume": "", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Micro-patterned culture of iPSC-derived alveolar and airway cells distinguishes SARS-CoV-2 variants.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "In amniote limbs, Fibroblast Growth Factor 10 (FGF10) is essential for limb development, but whether this function is broadly conserved in tetrapods and/or involved in adult limb regeneration remains unknown. To tackle this question, we established Fgf10 mutant lines in the newt Pleurodeles waltl which has amazing regenerative ability. While Fgf10 mutant forelimbs develop normally, the hindlimbs fail to develop and downregulate FGF target genes. Despite these developmental defects, Fgf10 mutants were able to regenerate normal hindlimbs rather than recapitulating the embryonic phenotype. Together, our results demonstrate an important role for FGF10 in hindlimb formation, but little or no function in regeneration, suggesting that different mechanisms operate during limb regeneration versus development.", "classifications": [ { "id": "JPMJCR2025", "label": "JPMJCR2025", "researcher": "Yoshihiro Morishita", "type": "grant" }, { "id": "Morishita", "label": "Group Morishita", "parent": "Morishita", "type": "group" }, { "id": "Morishita", "label": "Team Morishita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Miyuki", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Akinori", "last_name": "Okumura", "name": null }, { "creator_type": "author", "first_name": "Akane", "last_name": "Chihara", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Shibata", "name": null }, { "creator_type": "author", "first_name": "Tetsuya", "last_name": "Endo", "name": null }, { "creator_type": "author", "first_name": "Machiko", "last_name": "Teramoto", "name": null }, { "creator_type": "author", "first_name": "Kiyokazu", "last_name": "Agata", "name": null }, { "creator_type": "author", "first_name": "Marianne E.", "last_name": "Bronner", "name": null }, { "creator_type": "author", "first_name": "Ken-Ichi T.", "last_name": "Suzuki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1073/pnas.2314911121" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "38442169" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Fibroblast Growth Factor 10", "descriptor_ui": "D051526", "major_topic": true }, { "descriptor": "Hindlimb", "descriptor_ui": "D006614", "major_topic": false }, { "descriptor": "Pleurodeles", "descriptor_ui": "D010999", "major_topic": false }, { "descriptor": "Regeneration", "descriptor_ui": "D012038", "major_topic": false } ], "publication": { "conference_name": null, "date": "2024 Mar 12", "date_precision": "day", "issue": "11", "normalized_date": "2024-03-12", "pages": "e2314911121", "proceedings_title": null, "publisher": "", "title": "Proceedings of the National Academy of Sciences of the United States of America", "volume": "121", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Fgf10 mutant newts regenerate normal hindlimbs despite severe developmental defects.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "DNA methylation is an epigenetic modification that results in dynamic changes during ontogenesis and cell differentiation. DNA methylation patterns regulate gene expression and have been widely researched. While tools for DNA methylation analysis have been developed, most of them have focused on intergroup comparative analysis within a dataset; therefore, it is difficult to conduct cross-dataset studies, such as rare disease studies or cross-institutional studies. This study describes a novel method for DNA methylation analysis, namely, methPLIER, which enables interdataset comparative analyses. methPLIER combines Pathway Level Information Extractor (PLIER), which is a non-negative matrix factorization (NMF) method, with regularization by a knowledge matrix and transfer learning. methPLIER can be used to perform intersample and interdataset comparative analysis based on latent feature matrices, which are obtained via matrix factorization of large-scale data, and factor-loading matrices, which are obtained through matrix factorization of the data to be analyzed. We used methPLIER to analyze a lung cancer dataset and confirmed that the data decomposition reflected sample characteristics for recurrence-free survival. Moreover, methPLIER can analyze data obtained via different preprocessing methods, thereby reducing distributional bias among datasets due to preprocessing. Furthermore, methPLIER can be employed for comparative analyses of methylation data obtained from different platforms, thereby reducing bias in data distribution due to platform differences. methPLIER is expected to facilitate cross-sectional DNA methylation data analysis and enhance DNA methylation data resources.", "classifications": [ { "id": "Hamamoto", "label": "Group Hamamoto", "parent": "Okamoto", "type": "group" }, { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Ken", "last_name": "Takasawa", "name": null }, { "creator_type": "author", "first_name": "Ken", "last_name": "Asada", "name": null }, { "creator_type": "author", "first_name": "Syuzo", "last_name": "Kaneko", "name": null }, { "creator_type": "author", "first_name": "Kouya", "last_name": "Shiraishi", "name": null }, { "creator_type": "author", "first_name": "Hidenori", "last_name": "Machino", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Norio", "last_name": "Shinkai", "name": null }, { "creator_type": "author", "first_name": "Nobuji", "last_name": "Kouno", "name": null }, { "creator_type": "author", "first_name": "Kazuma", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Masaaki", "last_name": "Komatsu", "name": null }, { "creator_type": "author", "first_name": "Takaaki", "last_name": "Mizuno", "name": null }, { "creator_type": "author", "first_name": "Yu", "last_name": "Okubo", "name": null }, { "creator_type": "author", "first_name": "Masami", "last_name": "Mukai", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Yukihiro", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Hidehito", "last_name": "Horinouchi", "name": null }, { "creator_type": "author", "first_name": "Shun-Ichi", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Yuichiro", "last_name": "Ohe", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Kohno", "name": null }, { "creator_type": "author", "first_name": "Ryuji", "last_name": "Hamamoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s12276-024-01173-7" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "38433247" } }, "mesh": [ { "descriptor": "Algorithms", "descriptor_ui": "D000465", "major_topic": false }, { "descriptor": "Cross-Sectional Studies", "descriptor_ui": "D003430", "major_topic": false }, { "descriptor": "DNA Methylation", "descriptor_ui": "D019175", "major_topic": true }, { "descriptor": "Epigenesis, Genetic", "descriptor_ui": "D044127", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Neoplasms", "descriptor_ui": "D009369", "major_topic": true } ], "publication": { "conference_name": null, "date": "2024 Mar 4", "date_precision": "day", "issue": "", "normalized_date": "2024-03-04", "pages": "", "proceedings_title": null, "publisher": "", "title": "Experimental & molecular medicine", "volume": "", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Advances in cancer DNA methylation analysis with methPLIER: use of non-negative matrix factorization and knowledge-based constraints to enhance biological interpretability.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The clinical features of sporadic mismatch repair deficiency (MMRd) and Lynch syndrome (LS) in Japanese patients with endometrial cancer (EC) were examined by evaluating the prevalence and prognostic factors of LS and sporadic MMRd in patients with EC. Targeted sequencing of five LS susceptibility genes (MLH1, MSH2, MSH6, PMS2, and EPCAM) was carried out in 443 patients with EC who were pathologically diagnosed with EC at the National Cancer Center Hospital between 2011 and 2018. Pathogenic variants in these genes were detected in 16 patients (3.7%). Immunohistochemistry for MMR proteins was undertaken in 337 of the 433 (77.9%) EC patients, and 91 patients (27.0%) showed absent expression of at least one MMR protein. The 13 cases of LS with MMR protein loss (93.8%) showed a favorable prognosis with a 5-year overall survival (OS) rate of 100%, although there was no statistically significant difference between this group and the sporadic MMRd group (p = 0.27). In the MMRd without LS group, the 5-year OS rate was significantly worse in seven patients with an aberrant p53 expression pattern than in those with p53 WT (53.6% vs. 93.9%, log-rank test; p = 0.0016). These results suggest that p53 abnormalities and pathogenic germline variants in MMR genes could be potential biomarkers for the molecular classification of EC with MMRd.", "classifications": [ { "id": "Hamamoto", "label": "Group Hamamoto", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Mayumi Kobayashi", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Erisa", "last_name": "Fujii", "name": null }, { "creator_type": "author", "first_name": "Yuka", "last_name": "Asami", "name": null }, { "creator_type": "author", "first_name": "Yukihide", "last_name": "Momozawa", "name": null }, { "creator_type": "author", "first_name": "Kengo", "last_name": "Hiranuma", "name": null }, { "creator_type": "author", "first_name": "Masaaki", "last_name": "Komatsu", "name": null }, { "creator_type": "author", "first_name": "Ryuji", "last_name": "Hamamoto", "name": null }, { "creator_type": "author", "first_name": "Takahiro", "last_name": "Ebata", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Matsumoto", "name": null }, { "creator_type": "author", "first_name": "Mitsuya", "last_name": "Ishikawa", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Kohno", "name": null }, { "creator_type": "author", "first_name": "Tomoyasu", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Kouya", "last_name": "Shiraishi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/cas.16121" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "38433331" } }, "mesh": [ { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Aged, 80 and over", "descriptor_ui": "D000369", "major_topic": false }, { "descriptor": "Colorectal Neoplasms, Hereditary Nonpolyposis", "descriptor_ui": "D003123", "major_topic": true }, { "descriptor": "DNA Mismatch Repair", "descriptor_ui": "D053843", "major_topic": true }, { "descriptor": "DNA-Binding Proteins", "descriptor_ui": "D004268", "major_topic": false }, { "descriptor": "Endometrial Neoplasms", "descriptor_ui": "D016889", "major_topic": true }, { "descriptor": "Epithelial Cell Adhesion Molecule", "descriptor_ui": "D000071858", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Japan", "descriptor_ui": "D007564", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Mismatch Repair Endonuclease PMS2", "descriptor_ui": "D000070976", "major_topic": false }, { "descriptor": "MutL Protein Homolog 1", "descriptor_ui": "D000070957", "major_topic": false }, { "descriptor": "MutS Homolog 2 Protein", "descriptor_ui": "D051718", "major_topic": false }, { "descriptor": "Prognosis", "descriptor_ui": "D011379", "major_topic": false }, { "descriptor": "Tumor Suppressor Protein p53", "descriptor_ui": "D016159", "major_topic": true }, { "descriptor": "Uterine Neoplasms", "descriptor_ui": "D014594", "major_topic": true } ], "publication": { "conference_name": null, "date": "2024 Mar 3", "date_precision": "day", "issue": "", "normalized_date": "2024-03-03", "pages": "", "proceedings_title": null, "publisher": "", "title": "Cancer science", "volume": "", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Clinical features and impact of p53 status on sporadic mismatch repair deficiency and Lynch syndrome in uterine cancer.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The complex structures of multicellular organisms originate from a unicellular zygote. In most angiosperms, including Arabidopsis thaliana, the zygote is distinctly polar and divides asymmetrically to produce an apical cell, which generates the aboveground part of the plant body, and a basal cell, which generates the root tip and extraembryonic suspensor. Thus, zygote polarity is pivotal for establishing the apical-basal axis running from the shoot apex to the root tip of the plant body. The molecular mechanisms and spatiotemporal dynamics behind zygote polarization remain elusive. However, advances in live-cell imaging of plant zygotes have recently made significant insights possible. In this Cell Science at a Glance article and the accompanying poster, we summarize our understanding of the early steps in apical-basal axis formation in Arabidopsis, with a focus on de novo transcriptional activation after fertilization and the intracellular dynamics leading to the first asymmetric division of the zygote.", "classifications": [ { "id": "JPMJCR2121", "label": "JPMJCR2121", "researcher": "Minako Ueda", "type": "grant" }, { "id": "Ueda", "label": "Group Ueda", "parent": "Ueda", "type": "group" }, { "id": "Ueda", "label": "Team Ueda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Hikari", "last_name": "Matsumoto", "name": null }, { "creator_type": "author", "first_name": "Minako", "last_name": "Ueda", "name": null } ], "identifiers": { "doi": { "normalized": "10.1242/jcs.261809" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "38436556" } }, "mesh": [ { "descriptor": "Arabidopsis", "descriptor_ui": "D017360", "major_topic": true }, { "descriptor": "Meristem", "descriptor_ui": "D018519", "major_topic": false }, { "descriptor": "Seeds", "descriptor_ui": "D012639", "major_topic": false }, { "descriptor": "Transcriptional Activation", "descriptor_ui": "D015533", "major_topic": false }, { "descriptor": "Zygote", "descriptor_ui": "D015053", "major_topic": true } ], "publication": { "conference_name": null, "date": "2024 Mar 1", "date_precision": "day", "issue": "5", "normalized_date": "2024-03-01", "pages": "jcs261809", "proceedings_title": null, "publisher": "", "title": "Journal of cell science", "volume": "137", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Polarity establishment in the plant zygote at a glance.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "l-Lactate is a monocarboxylate produced during the process of cellular glycolysis and has long generally been considered a waste product. However, studies in recent decades have provided new perspectives on the physiological roles of l-lactate as a major energy substrate and a signaling molecule. To enable further investigations of the physiological roles of l-lactate, we have developed a series of high-performance (DeltaF/F = 15 to 30 in vitro), intensiometric, genetically encoded green fluorescent protein (GFP)-based intracellular l-lactate biosensors with a range of affinities. We evaluated these biosensors in cultured cells and demonstrated their application in an ex vivo preparation of Drosophila brain tissue. Using these biosensors, we were able to detect glycolytic oscillations, which we analyzed and mathematically modeled.", "classifications": [ { "id": "Kuroda", "label": "Group Kuroda", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Saaya", "last_name": "Hario", "name": null }, { "creator_type": "author", "first_name": "Giang N. T.", "last_name": "Le", "name": null }, { "creator_type": "author", "first_name": "Hikaru", "last_name": "Sugimoto", "name": null }, { "creator_type": "author", "first_name": "Kei", "last_name": "Takahashi-Yamashiro", "name": null }, { "creator_type": "author", "first_name": "Suguru", "last_name": "Nishinami", "name": null }, { "creator_type": "author", "first_name": "Hirofumi", "last_name": "Toda", "name": null }, { "creator_type": "author", "first_name": "Selene", "last_name": "Li", "name": null }, { "creator_type": "author", "first_name": "Jonathan S.", "last_name": "Marvin", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Kuroda", "name": null }, { "creator_type": "author", "first_name": "Mikhail", "last_name": "Drobizhev", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Terai", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Nasu", "name": null }, { "creator_type": "author", "first_name": "Robert E.", "last_name": "Campbell", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/acscentsci.3c01250" }, "pmcid": { "normalized": "PMC10906044" }, "pmid": { "normalized": "38435524" } }, "mesh": [], "publication": { "conference_name": null, "date": "2024 Feb 28", "date_precision": "day", "issue": "2", "normalized_date": "2024-02-28", "pages": "402-416", "proceedings_title": null, "publisher": "", "title": "ACS central science", "volume": "10", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "High-Performance Genetically Encoded Green Fluorescent Biosensors for Intracellular l-Lactate.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The length of long bones is determined by column formation of proliferative chondrocytes and subsequent chondrocyte hypertrophy in the growth plate during bone development. Despite the importance of mechanical loading in long bone development, the mechanical conditions of the cells within the growth plate, such as the stress field, remain unclear owing to the difficulty in investigating spatiotemporal changes within dynamically growing tissues. In this study, the mechanisms of longitudinal bone growth were investigated from a mechanical perspective through column formation of proliferative chondrocytes within the growth plate before the secondary ossification center formation using continuum-based particle models (CbPMs). A one-factor model, which simply describes essential aspects of a biological signaling cascade regulating cell activities within the growth plate, was developed and incorporated into CbPM. Subsequently, the developmental process and maintenance of the growth plate structure and resulting bone morphogenesis were simulated. Thus, stress anisotropy in the proliferative zone that affects bone elongation through chondrocyte column formation was identified and found to be promoted by chondrocyte hypertrophy. These results provide further insights into the mechanical regulation of multicellular dynamics during bone development.", "classifications": [ { "id": "Maki", "label": "Group Maki", "parent": "Toyoshima", "type": "group" }, { "id": "Toyoshima", "label": "Team Toyoshima", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yuka", "last_name": "Yokoyama", "name": null }, { "creator_type": "author", "first_name": "Yoshitaka", "last_name": "Kameo", "name": null }, { "creator_type": "author", "first_name": "Junko", "last_name": "Sunaga", "name": null }, { "creator_type": "author", "first_name": "Koichiro", "last_name": "Maki", "name": null }, { "creator_type": "author", "first_name": "Taiji", "last_name": "Adachi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.bone.2024.117055" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "38412894" } }, "mesh": [ { "descriptor": "Anisotropy", "descriptor_ui": "D016880", "major_topic": false }, { "descriptor": "Bone Development", "descriptor_ui": "D001846", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Chondrocytes", "descriptor_ui": "D019902", "major_topic": true }, { "descriptor": "Growth Plate", "descriptor_ui": "D006132", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Hypertrophy", "descriptor_ui": "D006984", "major_topic": false } ], "publication": { "conference_name": null, "date": "2024 Feb 25", "date_precision": "day", "issue": "", "normalized_date": "2024-02-25", "pages": "117055", "proceedings_title": null, "publisher": "", "title": "Bone", "volume": "", "year": 2024 }, "ssbd": { "database": [], "repository": [ "ssbd-repos-000432" ] }, "title": "Chondrocyte hypertrophy in the growth plate promotes stress anisotropy affecting long bone development through chondrocyte column formation.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Plasma membrane damage (PMD) occurs in all cell types due to environmental perturbation and cell-autonomous activities. However, cellular outcomes of PMD remain largely unknown except for recovery or death. In this study, using budding yeast and normal human fibroblasts, we found that cellular senescence-stable cell cycle arrest contributing to organismal aging-is the long-term outcome of PMD. Our genetic screening using budding yeast unexpectedly identified a close genetic association between PMD response and replicative lifespan regulations. Furthermore, PMD limits replicative lifespan in budding yeast; upregulation of membrane repair factors ESCRT-III (SNF7) and AAA-ATPase (VPS4) extends it. In normal human fibroblasts, PMD induces premature senescence via the Ca(2+)-p53 axis but not the major senescence pathway, DNA damage response pathway. Transient upregulation of ESCRT-III (CHMP4B) suppressed PMD-dependent senescence. Together with mRNA sequencing results, our study highlights an underappreciated but ubiquitous senescent cell subtype: PMD-dependent senescent cells.", "classifications": [ { "id": "Sato", "label": "Group Sato", "parent": "Tsuchiya", "type": "group" }, { "id": "Tsuchiya", "label": "Team Tsuchiya", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Kojiro", "last_name": "Suda", "name": null }, { "creator_type": "author", "first_name": "Yohsuke", "last_name": "Moriyama", "name": null }, { "creator_type": "author", "first_name": "Nurhanani", "last_name": "Razali", "name": null }, { "creator_type": "author", "first_name": "Yatzu", "last_name": "Chiu", "name": null }, { "creator_type": "author", "first_name": "Yumiko", "last_name": "Masukagami", "name": null }, { "creator_type": "author", "first_name": "Koutarou", "last_name": "Nishimura", "name": null }, { "creator_type": "author", "first_name": "Hunter", "last_name": "Barbee", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Takase", "name": null }, { "creator_type": "author", "first_name": "Shinju", "last_name": "Sugiyama", "name": null }, { "creator_type": "author", "first_name": "Yuta", "last_name": "Yamazaki", "name": null }, { "creator_type": "author", "first_name": "Yoshikatsu", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Tetsuya", "last_name": "Higashiyama", "name": null }, { "creator_type": "author", "first_name": "Yoshikazu", "last_name": "Johmura", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Nakanishi", "name": null }, { "creator_type": "author", "first_name": "Keiko", "last_name": "Kono", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s43587-024-00575-6" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "38388781" } }, "mesh": [ { "descriptor": "Adenosine Triphosphatases", "descriptor_ui": "D000251", "major_topic": false }, { "descriptor": "Cell Membrane", "descriptor_ui": "D002462", "major_topic": false }, { "descriptor": "Cellular Senescence", "descriptor_ui": "D016922", "major_topic": false }, { "descriptor": "Endosomal Sorting Complexes Required for Transport", "descriptor_ui": "D056827", "major_topic": false }, { "descriptor": "Fibroblasts", "descriptor_ui": "D005347", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Longevity", "descriptor_ui": "D008136", "major_topic": false }, { "descriptor": "Saccharomyces cerevisiae", "descriptor_ui": "D012441", "major_topic": true }, { "descriptor": "Saccharomyces cerevisiae Proteins", "descriptor_ui": "D029701", "major_topic": true }, { "descriptor": "Tumor Suppressor Protein p53", "descriptor_ui": "D016159", "major_topic": false } ], "publication": { "conference_name": null, "date": "2024 Feb 22", "date_precision": "day", "issue": "", "normalized_date": "2024-02-22", "pages": "", "proceedings_title": null, "publisher": "", "title": "Nature aging", "volume": "", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Plasma membrane damage limits replicative lifespan in yeast and induces premature senescence in human fibroblasts.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "OBJECTIVE: A significant number of patients experience early recurrence after surgical resection for pancreatic ductal adenocarcinoma (PDAC), negating the benefit of surgery. The present study conducted clinicopathologic and metabolomic analyses to explore the factors associated with the early recurrence of PDAC. MATERIALS AND METHODS: Patients who underwent pancreatectomy for PDAC at Kagawa University Hospital between 2011 and 2020 were enrolled. Tissue samples of PDAC and nonneoplastic pancreas were collected and frozen immediately after resection. Charged metabolites were quantified by capillary electrophoresis-mass spectrometry. Patients who relapsed within 1 year were defined as the early recurrence group. RESULTS: Frozen tumor tissue and nonneoplastic pancreas were collected from 79 patients. The clinicopathologic analysis identified 11 predictive factors, including preoperative carbohydrate antigen 19-9 levels. The metabolomic analysis revealed that only hypotaurine was a significant risk factor for early recurrence. A multivariate analysis, including clinical and metabolic factors, showed that carbohydrate antigen 19-9 and hypotaurine were independent risk factors for early recurrence (P = 0.045 and P = 0.049, respectively). The recurrence-free survival rate 1 year after surgery with both risk factors was only 25%. CONCLUSIONS: Our results suggested that tumor hypotaurine is a potential metabolite associated with early recurrence. Carbohydrate antigen 19-9 and hypotaurine showed a vital utility for predicting early recurrence.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Mina", "last_name": "Nagao", "name": null }, { "creator_type": "author", "first_name": "Minoru", "last_name": "Oshima", "name": null }, { "creator_type": "author", "first_name": "Hironobu", "last_name": "Suto", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Sugimoto", "name": null }, { "creator_type": "author", "first_name": "Ayame", "last_name": "Enomoto", "name": null }, { "creator_type": "author", "first_name": "Tomomasa", "last_name": "Murakami", "name": null }, { "creator_type": "author", "first_name": "Ayaka", "last_name": "Shimomura", "name": null }, { "creator_type": "author", "first_name": "Yukiko", "last_name": "Wada", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Matsukawa", "name": null }, { "creator_type": "author", "first_name": "Yasuhisa", "last_name": "Ando", "name": null }, { "creator_type": "author", "first_name": "Takayoshi", "last_name": "Kishino", "name": null }, { "creator_type": "author", "first_name": "Kensuke", "last_name": "Kumamoto", "name": null }, { "creator_type": "author", "first_name": "Hideki", "last_name": "Kobara", "name": null }, { "creator_type": "author", "first_name": "Hideki", "last_name": "Kamada", "name": null }, { "creator_type": "author", "first_name": "Tsutomu", "last_name": "Masaki", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Keiichi", "last_name": "Okano", "name": null } ], "identifiers": { "doi": { "normalized": "10.1097/mpa.0000000000002304" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "38373081" } }, "mesh": [ { "descriptor": "CA-19-9 Antigen", "descriptor_ui": "D018395", "major_topic": false }, { "descriptor": "Carbohydrates", "descriptor_ui": "D002241", "major_topic": false }, { "descriptor": "Carcinoma, Pancreatic Ductal", "descriptor_ui": "D021441", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Neoplasm Recurrence, Local", "descriptor_ui": "D009364", "major_topic": false }, { "descriptor": "Pancreas", "descriptor_ui": "D010179", "major_topic": false }, { "descriptor": "Pancreatectomy", "descriptor_ui": "D010180", "major_topic": false }, { "descriptor": "Pancreatic Neoplasms", "descriptor_ui": "D010190", "major_topic": true }, { "descriptor": "Prognosis", "descriptor_ui": "D011379", "major_topic": false }, { "descriptor": "Retrospective Studies", "descriptor_ui": "D012189", "major_topic": false }, { "descriptor": "Taurine", "descriptor_ui": "D013654", "major_topic": false } ], "publication": { "conference_name": null, "date": "2024 Feb 20", "date_precision": "day", "issue": "", "normalized_date": "2024-02-20", "pages": "", "proceedings_title": null, "publisher": "", "title": "Pancreas", "volume": "", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Serum Carbohydrate Antigen 19-9 and Metabolite Hypotaurine Are Predictive Markers for Early Recurrence of Pancreatic Ductal Adenocarcinoma.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "This perspective highlights advances in the preparation and understanding of metal nanoclusters stabilized by organic ligands with a focus on N-heterocyclic carbenes (NHCs). We demonstrate the need for a clear understanding of the relationship between NHC properties and their resulting metal nanocluster structure and properties. We emphasize the importance of balancing nanocluster stability with the introduction of reactive sites for catalytic applications and the importance of a better understanding of how these clusters interact with their environments for effective use in biological applications. The impact of atom-scale simulations, development of atomic interaction potentials suitable for large-scale molecular dynamics simulations, and a deeper understanding of the mechanisms behind synthetic methods and physical properties (e.g., the bright fluorescence displayed by many clusters) are emphasized.", "classifications": [ { "id": "Nanbo", "label": "Group Nanbo", "parent": "Tsuchiya", "type": "group" }, { "id": "Tsuchiya", "label": "Team Tsuchiya", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Emily L.", "last_name": "Albright", "name": null }, { "creator_type": "author", "first_name": "Tetyana I.", "last_name": "Levchenko", "name": null }, { "creator_type": "author", "first_name": "Viveka K.", "last_name": "Kulkarni", "name": null }, { "creator_type": "author", "first_name": "Angus I.", "last_name": "Sullivan", "name": null }, { "creator_type": "author", "first_name": "Joseph F.", "last_name": "DeJesus", "name": null }, { "creator_type": "author", "first_name": "Sami", "last_name": "Malola", "name": null }, { "creator_type": "author", "first_name": "Shinjiro", "last_name": "Takano", "name": null }, { "creator_type": "author", "first_name": "Masakazu", "last_name": "Nambo", "name": null }, { "creator_type": "author", "first_name": "Kevin", "last_name": "Stamplecoskie", "name": null }, { "creator_type": "author", "first_name": "Hannu", "last_name": "Hakkinen", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Tsukuda", "name": null }, { "creator_type": "author", "first_name": "Cathleen M.", "last_name": "Crudden", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/jacs.3c11031" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "38373254" } }, "mesh": [], "publication": { "conference_name": null, "date": "2024 Feb 19", "date_precision": "day", "issue": "", "normalized_date": "2024-02-19", "pages": "", "proceedings_title": null, "publisher": "", "title": "Journal of the American Chemical Society", "volume": "", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "N-Heterocyclic Carbene-Stabilized Atomically Precise Metal Nanoclusters.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "INTRODUCTION: The International Agency for Research on Cancer has classified passive smoking (PS) or secondhand smoke exposure as a Group 1 carcinogen linked to lung cancer; however, in contrast to active smoking, the mutagenic properties of PS remain unclear. METHODS: A consecutive cohort of 564 lung adenocarcinoma samples from female never-smokers, who provided detailed information about their exposure to PS during adolescence and in their thirties through a questionnaire, was prepared. Of these, all 291 cases for whom frozen tumor tissues were available were subjected to whole exome sequencing to estimate tumor mutational burden (TMB), and the top 84 cases who were exposed daily, or not, to PS during adolescence and/or in their thirties were further subjected to whole genome sequencing. RESULTS: A modest yet statistically significant increase in TMB was observed in the group exposed to PS compared with the group not exposed to PS (median values = 1.44 vs. 1.29 per Mb, respectively; p = 0.020). Instead of inducing driver oncogene mutations, PS induced significant subclonal mutations exhibiting APOBEC-type signatures, including SMAD4 and ADGRG6 hotspot mutations. A polymorphic APOBEC3A/3B allele specific to the Asian population that leads to upregulated expression of APOBEC3A accentuated the mutational load in individuals exposed daily to PS during adolescence. CONCLUSIONS: This study reveals that passive smoking-induced mutagenesis can promote lung carcinogenesis. The APOBEC3A/3B polymorphism may serve as a biomarker for identifying passive non-smoking individuals at high-risk of developing lung cancer.", "classifications": [ { "id": "Hamamoto", "label": "Group Hamamoto", "parent": "Okamoto", "type": "group" }, { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Akifumi", "last_name": "Mochizuki", "name": null }, { "creator_type": "author", "first_name": "Kouya", "last_name": "Shiraishi", "name": null }, { "creator_type": "author", "first_name": "Takayuki", "last_name": "Honda", "name": null }, { "creator_type": "author", "first_name": "Ryoko Inaba", "last_name": "Higashiyama", "name": null }, { "creator_type": "author", "first_name": "Kuniko", "last_name": "Sunami", "name": null }, { "creator_type": "author", "first_name": "Maiko", "last_name": "Matsuda", "name": null }, { "creator_type": "author", "first_name": "Yoko", "last_name": "Shimada", "name": null }, { "creator_type": "author", "first_name": "Yasunari", "last_name": "Miyazaki", "name": null }, { "creator_type": "author", "first_name": "Yukihiro", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Shun-Ichi", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null }, { "creator_type": "author", "first_name": "Ryuji", "last_name": "Hamamoto", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Kohno", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.jtho.2024.02.006" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "38382595" } }, "mesh": [ { "descriptor": "Adenocarcinoma of Lung", "descriptor_ui": "D000077192", "major_topic": false }, { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Carcinogenesis", "descriptor_ui": "D063646", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Lung Neoplasms", "descriptor_ui": "D008175", "major_topic": true }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Mutagenesis", "descriptor_ui": "D016296", "major_topic": false }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": false }, { "descriptor": "Tobacco Smoke Pollution", "descriptor_ui": "D014028", "major_topic": true } ], "publication": { "conference_name": null, "date": "2024 Feb 19", "date_precision": "day", "issue": "", "normalized_date": "2024-02-19", "pages": "S1556-0864(24)00074-1", "proceedings_title": null, "publisher": "", "title": "Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer", "volume": "", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Passive smoking-induced mutagenesis as a promoter of lung carcinogenesis.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "We recently reported that transient receptor potential canonical (TRPC) 6 channel activity contributes to intracellular Zn(2+) homeostasis in the heart. Zn(2+) has also been implicated in the regulation of intestinal redox and microbial homeostasis. This study aims to investigate the role of TRPC6-mediated Zn(2+) influx in the stress resistance of the intestine. The expression profile of TRPC1-C7 mRNAs in the actively inflamed mucosa from inflammatory bowel disease (IBD) patients was analyzed using the GEO database. Systemic TRPC3 knockout (KO) and TRPC6 KO mice were treated with dextran sulfate sodium (DSS) to induce colitis. The Zn(2+) concentration and the mRNA expression levels of oxidative/inflammatory markers in colon tissues were quantitatively analyzed, and gut microbiota profiles were compared. TRPC6 mRNA expression level was increased in IBD patients and DSS-treated mouse colon tissues. DSS-treated TRPC6 KO mice, but not TRPC3 KO mice, showed severe weight loss and increased disease activity index compared with DSS-treated WT mice. The mRNA abundances of antioxidant proteins were basically increased in the TRPC6 KO colon, with changes in gut microbiota profiles. Treatment with TRPC6 activator prevented the DSS-induced colitis progression accompanied by increasing Zn(2+) concentration. We suggest that TRPC6-mediated Zn(2+) influx activity plays a key role in stress resistance against IBD, providing a new strategy for treating colitis.", "classifications": [ { "id": "JPMJCR2024", "label": "JPMJCR2024", "researcher": "Motohiro Nishida", "type": "grant" }, { "id": "Nishida", "label": "Group Nishida", "parent": "Nishida", "type": "group" }, { "id": "Nishimura", "label": "Group Nishimura", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Kazuhiro", "last_name": "Nishiyama", "name": null }, { "creator_type": "author", "first_name": "Yuri", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Akiyuki", "last_name": "Nishimura", "name": null }, { "creator_type": "author", "first_name": "Xinya", "last_name": "Mi", "name": null }, { "creator_type": "author", "first_name": "Ryu", "last_name": "Nagata", "name": null }, { "creator_type": "author", "first_name": "Yasuo", "last_name": "Mori", "name": null }, { "creator_type": "author", "first_name": "Yasu-Taka", "last_name": "Azuma", "name": null }, { "creator_type": "author", "first_name": "Motohiro", "last_name": "Nishida", "name": null } ], "identifiers": { "doi": { "normalized": "10.3390/ijms25042401" }, "pmcid": { "normalized": "PMC10889536" }, "pmid": { "normalized": "38397074" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Colon", "descriptor_ui": "D003106", "major_topic": false }, { "descriptor": "Dextran Sulfate", "descriptor_ui": "D016264", "major_topic": false }, { "descriptor": "Disease Models, Animal", "descriptor_ui": "D004195", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Inflammatory Bowel Diseases", "descriptor_ui": "D015212", "major_topic": true }, { "descriptor": "Intestines", "descriptor_ui": "D007422", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "RNA, Messenger", "descriptor_ui": "D012333", "major_topic": false }, { "descriptor": "TRPC6 Cation Channel", "descriptor_ui": "D000074287", "major_topic": true } ], "publication": { "conference_name": null, "date": "2024 Feb 18", "date_precision": "day", "issue": "4", "normalized_date": "2024-02-18", "pages": "", "proceedings_title": null, "publisher": "", "title": "International journal of molecular sciences", "volume": "25", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Pharmacological Activation of TRPC6 Channel Prevents Colitis Progression.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Myeloid cells, which originate from hematopoietic stem/progenitor cells (HSPCs), play a crucial role in mitigating infections. This study aimed to explore the impact of mesenchymal stem/stromal cells (MSCs) on the differentiation of HSPCs and progenitors through the C-C motif chemokine CCL2/CCR2 signaling pathway. Murine MSCs, identified as PDGFRalpha(+)Sca-1(+) cells (PalphaS cells), were found to secrete CCL2, particularly in response to lipopolysaccharide stimulation. MSC-secreted CCL2 promoted the differentiation of granulocyte/macrophage progenitors into the myeloid lineage. MSC-derived CCL2 plays an important role in the early phase of myeloid cell differentiation in vivo. Single-cell RNA sequencing analysis confirmed that CCL2-mediated cell fate determination was also observed in human bone marrow cells. These findings provide valuable insights for investigating the in vivo effects of MSC transplantation.", "classifications": [ { "id": "JPMJCR2124", "label": "JPMJCR2124", "researcher": "Hirofumi Shintaku", "type": "grant" }, { "id": "Nishikii", "label": "Group Nishikii", "parent": "Shintaku", "type": "group" }, { "id": "Shintaku", "label": "Group Shintaku", "parent": "Shintaku", "type": "group" }, { "id": "Shintaku", "label": "Team Shintaku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Satoshi", "last_name": "Yamazaki", "name": null }, { "creator_type": "author", "first_name": "Yo", "last_name": "Mabuchi", "name": null }, { "creator_type": "author", "first_name": "Takaharu", "last_name": "Kimura", "name": null }, { "creator_type": "author", "first_name": "Eriko Grace", "last_name": "Suto", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Hisamatsu", "name": null }, { "creator_type": "author", "first_name": "Yuna", "last_name": "Naraoka", "name": null }, { "creator_type": "author", "first_name": "Ayako", "last_name": "Kondo", "name": null }, { "creator_type": "author", "first_name": "Yuzuki", "last_name": "Azuma", "name": null }, { "creator_type": "author", "first_name": "Riko", "last_name": "Kikuchi", "name": null }, { "creator_type": "author", "first_name": "Hidekazu", "last_name": "Nishikii", "name": null }, { "creator_type": "author", "first_name": "Soji", "last_name": "Morishita", "name": null }, { "creator_type": "author", "first_name": "Marito", "last_name": "Araki", "name": null }, { "creator_type": "author", "first_name": "Norio", "last_name": "Komatsu", "name": null }, { "creator_type": "author", "first_name": "Chihiro", "last_name": "Akazawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.stemcr.2024.02.002" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "38428413" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Chemokine CCL2", "descriptor_ui": "D018932", "major_topic": true }, { "descriptor": "Hematopoietic Stem Cells", "descriptor_ui": "D006412", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mesenchymal Stem Cells", "descriptor_ui": "D059630", "major_topic": true }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Receptors, CCR2", "descriptor_ui": "D054390", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false } ], "publication": { "conference_name": null, "date": "2024 Feb 16", "date_precision": "day", "issue": "", "normalized_date": "2024-02-16", "pages": "S2213-6711(24)00014-6", "proceedings_title": null, "publisher": "", "title": "Stem cell reports", "volume": "", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Activated mesenchymal stem/stromal cells promote myeloid cell differentiation via CCL2/CCR2 signaling.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Early patterning of neural crest cells (NCCs) in the craniofacial primordium is important for subsequent development of proper craniofacial structures. However, because of the complexity of the environment of developing tissues, surveying the early specification and patterning of NCCs is difficult. In this study, we develop a simplified in vitro 3D model using human pluripotent stem cells to analyze the early stages of facial development. In this model, cranial NCC-like cells spontaneously differentiate from neural plate border-like cells into maxillary arch-like mesenchyme after a long-term culture. Upon the addition of EDN1 and BMP4, these aggregates are converted into a mandibular arch-like state. Furthermore, temporary treatment with EDN1 and BMP4 induces the formation of spatially separated domains expressing mandibular and maxillary arch markers within a single aggregate. These results suggest that this in vitro model is useful for determining the mechanisms underlying cell fate specification and patterning during early facial development.", "classifications": [ { "id": "Eiraku", "label": "Group Eiraku", "parent": "Eiraku", "type": "group" }, { "id": "Eiraku", "label": "Team Eiraku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yusuke", "last_name": "Seto", "name": null }, { "creator_type": "author", "first_name": "Ryoma", "last_name": "Ogihara", "name": null }, { "creator_type": "author", "first_name": "Kaori", "last_name": "Takizawa", "name": null }, { "creator_type": "author", "first_name": "Mototsugu", "last_name": "Eiraku", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41467-024-45285-0" }, "pmcid": { "normalized": "PMC10867012" }, "pmid": { "normalized": "38355589" } }, "mesh": [ { "descriptor": "Branchial Region", "descriptor_ui": "D001934", "major_topic": true }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mandible", "descriptor_ui": "D008334", "major_topic": false }, { "descriptor": "Neural Crest", "descriptor_ui": "D009432", "major_topic": false }, { "descriptor": "Pluripotent Stem Cells", "descriptor_ui": "D039904", "major_topic": true } ], "publication": { "conference_name": null, "date": "2024 Feb 14", "date_precision": "day", "issue": "1", "normalized_date": "2024-02-14", "pages": "1351", "proceedings_title": null, "publisher": "", "title": "Nature communications", "volume": "15", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "In vitro induction of patterned branchial arch-like aggregate from human pluripotent stem cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "", "classifications": [ { "id": "Yamamoto", "label": "Group Yamamoto", "parent": "Toyoshima", "type": "group" }, { "id": "Toyoshima", "label": "Team Toyoshima", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Takumi", "last_name": "Okubo", "name": null }, { "creator_type": "author", "first_name": "Nicolas", "last_name": "Rivron", "name": null }, { "creator_type": "author", "first_name": "Mio", "last_name": "Kabata", "name": null }, { "creator_type": "author", "first_name": "Hideki", "last_name": "Masaki", "name": null }, { "creator_type": "author", "first_name": "Keiko", "last_name": "Kishimoto", "name": null }, { "creator_type": "author", "first_name": "Katsunori", "last_name": "Semi", "name": null }, { "creator_type": "author", "first_name": "May", "last_name": "Nakajima-Koyama", "name": null }, { "creator_type": "author", "first_name": "Haruko", "last_name": "Kunitomi", "name": null }, { "creator_type": "author", "first_name": "Belinda", "last_name": "Kaswandy", "name": null }, { "creator_type": "author", "first_name": "Hideyuki", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Hiromitsu", "last_name": "Nakauchi", "name": null }, { "creator_type": "author", "first_name": "Knut", "last_name": "Woltjen", "name": null }, { "creator_type": "author", "first_name": "Mitinori", "last_name": "Saitou", "name": null }, { "creator_type": "author", "first_name": "Erika", "last_name": "Sasaki", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Yasuhiro", "last_name": "Takashima", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41586-024-07166-w" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "38347193" } }, "mesh": [], "publication": { "conference_name": null, "date": "2024 Feb 12", "date_precision": "day", "issue": "", "normalized_date": "2024-02-12", "pages": "", "proceedings_title": null, "publisher": "", "title": "Nature", "volume": "", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Publisher Correction: Hypoblast from human pluripotent stem cells regulates epiblast development.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Together with the molecular knowledge of genes and proteins, biological images promise to significantly enhance the scientific understanding of complex cellular systems and to advance predictive and personalized therapeutic products for human health. For this potential to be realized, quality-assured image data must be shared among labs at a global scale to be compared, pooled, and reanalyzed, thus unleashing untold potential beyond the original purpose for which the data was generated. There are two broad sets of requirements to enable image data sharing in the life sciences. One set of requirements is articulated in the companion White Paper entitled \"Enabling Global Image Data Sharing in the Life Sciences,\" which is published in parallel and addresses the need to build the cyberinfrastructure for sharing the digital array data (arXiv:2401.13023 [q-bio.OT], https://doi.org/10.48550/arXiv.2401.13023). In this White Paper, we detail a broad set of requirements, which involves collecting, managing, presenting, and propagating contextual information essential to assess the quality, understand the content, interpret the scientific implications, and reuse image data in the context of the experimental details. We start by providing an overview of the main lessons learned to date through international community activities, which have recently made considerable progress toward generating community standard practices for imaging Quality Control (QC) and metadata. We then provide a clear set of recommendations for amplifying this work. The driving goal is to address remaining challenges, and democratize access to common practices and tools for a spectrum of biomedical researchers, regardless of their expertise, access to resources, and geographical location.", "classifications": [ { "id": "Onami", "label": "Group Onami", "parent": "Fujiwara", "type": "group" }, { "id": "Fujiwara", "label": "Team Fujiwara", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Nikki", "last_name": "Bialy", "name": null }, { "creator_type": "author", "first_name": "Frank", "last_name": "Alber", "name": null }, { "creator_type": "author", "first_name": "Brenda", "last_name": "Andrews", "name": null }, { "creator_type": "author", "first_name": "Michael", "last_name": "Angelo", "name": null }, { "creator_type": "author", "first_name": "Brian", "last_name": "Beliveau", "name": null }, { "creator_type": "author", "first_name": "Lacramioara", "last_name": "Bintu", "name": null }, { "creator_type": "author", "first_name": "Alistair", "last_name": "Boettiger", "name": null }, { "creator_type": "author", "first_name": "Ulrike", "last_name": "Boehm", "name": null }, { "creator_type": "author", "first_name": "Claire M.", "last_name": "Brown", "name": null }, { "creator_type": "author", "first_name": "Mahmoud Bukar", "last_name": "Maina", "name": null }, { "creator_type": "author", "first_name": "James J.", "last_name": "Chambers", "name": null }, { "creator_type": "author", "first_name": "Beth A.", "last_name": "Cimini", "name": null }, { "creator_type": "author", "first_name": "Kevin", "last_name": "Eliceiri", "name": null }, { "creator_type": "author", "first_name": "Rachel", "last_name": "Errington", "name": null }, { "creator_type": "author", "first_name": "Orestis", "last_name": "Faklaris", "name": null }, { "creator_type": "author", "first_name": "Nathalie", "last_name": "Gaudreault", "name": null }, { "creator_type": "author", "first_name": "Ronald N.", "last_name": "Germain", "name": null }, { "creator_type": "author", "first_name": "Wojtek", "last_name": "Goscinski", "name": null }, { "creator_type": "author", "first_name": "David", "last_name": "Grunwald", "name": null }, { "creator_type": "author", "first_name": "Michael", "last_name": "Halter", "name": null }, { "creator_type": "author", "first_name": "Dorit", "last_name": "Hanein", "name": null }, { "creator_type": "author", "first_name": "John W.", "last_name": "Hickey", "name": null }, { "creator_type": "author", "first_name": "Judith", "last_name": "Lacoste", "name": null }, { "creator_type": "author", "first_name": "Alex", "last_name": "Laude", "name": null }, { "creator_type": "author", "first_name": "Emma", "last_name": "Lundberg", "name": null }, { "creator_type": "author", "first_name": "Jian", "last_name": "Ma", "name": null }, { "creator_type": "author", "first_name": "Leonel", "last_name": "Malacrida", "name": null }, { "creator_type": "author", "first_name": "Josh", "last_name": "Moore", "name": null }, { "creator_type": "author", "first_name": "Glyn", "last_name": "Nelson", "name": null }, { "creator_type": "author", "first_name": "Elizabeth Kathleen", "last_name": "Neumann", "name": null }, { "creator_type": "author", "first_name": "Roland", "last_name": "Nitschke", "name": null }, { "creator_type": "author", "first_name": "Shuichi", "last_name": "Onami", "name": null }, { "creator_type": "author", "first_name": "Jaime A.", "last_name": "Pimentel", "name": null }, { "creator_type": "author", "first_name": "Anne L.", "last_name": "Plant", "name": null }, { "creator_type": "author", "first_name": "Andrea J.", "last_name": "Radtke", "name": null }, { "creator_type": "author", "first_name": "Bikash", "last_name": "Sabata", "name": null }, { "creator_type": "author", "first_name": "Denis", "last_name": "Schapiro", "name": null }, { "creator_type": "author", "first_name": "Johannes", "last_name": "Schoneberg", "name": null }, { "creator_type": "author", "first_name": "Jeffrey M.", "last_name": "Spraggins", "name": null }, { "creator_type": "author", "first_name": "Damir", "last_name": "Sudar", "name": null }, { "creator_type": "author", "first_name": "Wouter-Michiel", "last_name": "Adrien Maria Vierdag", "name": null }, { "creator_type": "author", "first_name": "Niels", "last_name": "Volkmann", "name": null }, { "creator_type": "author", "first_name": "Carolina", "last_name": "Wahlby", "name": null }, { "creator_type": "author", "first_name": "Siyuan Steven", "last_name": "Wang", "name": null }, { "creator_type": "author", "first_name": "Ziv", "last_name": "Yaniv", "name": null }, { "creator_type": "author", "first_name": "Caterina", "last_name": "Strambio-De-Castillia", "name": null } ], "identifiers": { "doi": { "normalized": "10.48550/arxiv.2401.13022" }, "pmcid": { "normalized": null }, "pmid": { "normalized": null } }, "mesh": [], "publication": { "conference_name": null, "date": "2024 Feb 8", "date_precision": "day", "issue": null, "normalized_date": "2024-02-08", "pages": null, "proceedings_title": null, "publisher": null, "title": null, "volume": null, "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Harmonizing the Generation and Pre-publication Stewardship of FAIR Image data.", "url": "", "zotero": { "item_type": "preprint" } }, { "abstract": "Nuclear pore complexes (NPCs) on the nuclear membrane surface have a crucial function in controlling the movement of small molecules and macromolecules between the cell nucleus and cytoplasm through their intricate core channel resembling a spiderweb with several layers. Currently, there are few methods available to accurately measure the dynamics of nuclear pores on the nuclear membranes at the nanoscale. The limitation of traditional optical imaging is due to diffraction, which prevents achieving the required resolution for observing a diverse array of organelles and proteins within cells. Super-resolution techniques have effectively addressed this constraint by enabling the observation of subcellular components on the nanoscale. Nevertheless, it is crucial to acknowledge that these methods often need the use of fixed samples. This also raises the question of how closely a static image represents the real intracellular dynamic system. High-speed atomic force microscopy (HS-AFM) is a unique technique used in the field of dynamic structural biology, enabling the study of individual molecules in motion close to their native states. Establishing a reliable and repeatable technique for imaging mammalian tissue at the nanoscale using HS-AFM remains challenging due to inadequate sample preparation. This study presents the rapid strainer microfiltration (RSM) protocol for directly preparing high-quality nuclei from the mouse brain. Subsequently, we promptly utilize HS-AFM real-time imaging and cinematography approaches to record the spatiotemporal of nuclear pore nano-dynamics from the mouse brain.", "classifications": [ { "id": "Inaba", "label": "Group Inaba", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yujia", "last_name": "Qiu", "name": null }, { "creator_type": "author", "first_name": "Elma Sakinatus", "last_name": "Sajidah", "name": null }, { "creator_type": "author", "first_name": "Sota", "last_name": "Kondo", "name": null }, { "creator_type": "author", "first_name": "Shinnosuke", "last_name": "Narimatsu", "name": null }, { "creator_type": "author", "first_name": "Muhammad Isman", "last_name": "Sandira", "name": null }, { "creator_type": "author", "first_name": "Yoshiki", "last_name": "Higashiguchi", "name": null }, { "creator_type": "author", "first_name": "Goro", "last_name": "Nishide", "name": null }, { "creator_type": "author", "first_name": "Azuma", "last_name": "Taoka", "name": null }, { "creator_type": "author", "first_name": "Masaharu", "last_name": "Hazawa", "name": null }, { "creator_type": "author", "first_name": "Yuka", "last_name": "Inaba", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Inoue", "name": null }, { "creator_type": "author", "first_name": "Ayami", "last_name": "Matsushima", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Okada", "name": null }, { "creator_type": "author", "first_name": "Mitsutoshi", "last_name": "Nakada", "name": null }, { "creator_type": "author", "first_name": "Toshio", "last_name": "Ando", "name": null }, { "creator_type": "author", "first_name": "Keesiang", "last_name": "Lim", "name": null }, { "creator_type": "author", "first_name": "Richard W.", "last_name": "Wong", "name": null } ], "identifiers": { "doi": { "normalized": "10.3390/cells13030279" }, "pmcid": { "normalized": "PMC10855070" }, "pmid": { "normalized": "38334671" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Brain", "descriptor_ui": "D001921", "major_topic": false }, { "descriptor": "Cell Nucleus", "descriptor_ui": "D002467", "major_topic": false }, { "descriptor": "Mammals", "descriptor_ui": "D008322", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Microscopy, Atomic Force", "descriptor_ui": "D018625", "major_topic": false }, { "descriptor": "Proteins", "descriptor_ui": "D011506", "major_topic": true }, { "descriptor": "Single Molecule Imaging", "descriptor_ui": "D000072760", "major_topic": true } ], "publication": { "conference_name": null, "date": "2024 Feb 2", "date_precision": "day", "issue": "3", "normalized_date": "2024-02-02", "pages": "", "proceedings_title": null, "publisher": "", "title": "Cells", "volume": "13", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "An Efficient Method for Isolating and Purifying Nuclei from Mice Brain for Single-Molecule Imaging Using High-Speed Atomic Force Microscopy.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "AIMS: Nonalcoholic fatty liver disease (NAFLD) is known to be associated with atherosclerosis. This study focused on upstream changes in the process by which NAFLD leads to atherosclerosis. The study aimed to confirm the association between NAFLD and the cardio-ankle vascular index (CAVI), an indicator of subclinical atherosclerosis, and explore metabolites involved in both by assessing 94 plasma polar metabolites. METHODS: A total of 928 Japanese community-dwellers (306 men and 622 women) were included in this study. The association between NAFLD and CAVI was examined using a multivariable regression model adjusted for confounders. Metabolites commonly associated with NAFLD and CAVI were investigated using linear mixed-effects models in which batch numbers of metabolite measurements were used as a random-effects variable, and false discovery rate-adjusted p-values were calculated. To determine the extent to which these metabolites mediated the association between NAFLD and CAVI, mediation analysis was conducted. RESULTS: NAFLD was positively associated with CAVI (coefficients [95% Confidence intervals (CI)]=0.23 [0.09-0.37]; p=0.001). A total of 10 metabolites were involved in NAFLD and CAVI, namely, branched-chain amino acids (BCAAs; valine, leucine, and isoleucine), aromatic amino acids (AAAs; tyrosine and tryptophan), alanine, proline, glutamic acid, glycerophosphorylcholine, and 4-methyl-2-oxopentanoate. Mediation analysis showed that BCAAs mediated more than 20% of the total effect in the association between NAFLD and CAVI. CONCLUSIONS: NAFLD was associated with a marker of atherosclerosis, and several metabolites related to insulin resistance, including BCAAs and AAAs, could be involved in the process by which NAFLD leads to atherosclerosis.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Aya", "last_name": "Hirata", "name": null }, { "creator_type": "author", "first_name": "Sei", "last_name": "Harada", "name": null }, { "creator_type": "author", "first_name": "Miho", "last_name": "Iida", "name": null }, { "creator_type": "author", "first_name": "Ayako", "last_name": "Kurihara", "name": null }, { "creator_type": "author", "first_name": "Kota", "last_name": "Fukai", "name": null }, { "creator_type": "author", "first_name": "Kazuyo", "last_name": "Kuwabara", "name": null }, { "creator_type": "author", "first_name": "Suzuka", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Minako", "last_name": "Matsumoto", "name": null }, { "creator_type": "author", "first_name": "Mizuki", "last_name": "Sata", "name": null }, { "creator_type": "author", "first_name": "Naoko", "last_name": "Miyagawa", "name": null }, { "creator_type": "author", "first_name": "Ryota", "last_name": "Toki", "name": null }, { "creator_type": "author", "first_name": "Shun", "last_name": "Edagawa", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Sugiyama", "name": null }, { "creator_type": "author", "first_name": "Asako", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Akiyoshi", "last_name": "Hirayama", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Sugimoto", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Masaru", "last_name": "Tomita", "name": null }, { "creator_type": "author", "first_name": "Tomonori", "last_name": "Okamura", "name": null }, { "creator_type": "author", "first_name": "Toru", "last_name": "Takebayashi", "name": null } ], "identifiers": { "doi": { "normalized": "10.5551/jat.64616" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "38311416" } }, "mesh": [ { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Ankle Brachial Index", "descriptor_ui": "D055109", "major_topic": false }, { "descriptor": "Atherosclerosis", "descriptor_ui": "D050197", "major_topic": false }, { "descriptor": "Biomarkers", "descriptor_ui": "D015415", "major_topic": false }, { "descriptor": "East Asian People", "descriptor_ui": "D000095225", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Independent Living", "descriptor_ui": "D057187", "major_topic": false }, { "descriptor": "Japan", "descriptor_ui": "D007564", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Metabolomics", "descriptor_ui": "D055432", "major_topic": true }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Non-alcoholic Fatty Liver Disease", "descriptor_ui": "D065626", "major_topic": true }, { "descriptor": "Prognosis", "descriptor_ui": "D011379", "major_topic": false }, { "descriptor": "Vascular Stiffness", "descriptor_ui": "D059289", "major_topic": true } ], "publication": { "conference_name": null, "date": "2024 Feb 2", "date_precision": "day", "issue": "", "normalized_date": "2024-02-02", "pages": "", "proceedings_title": null, "publisher": "", "title": "Journal of atherosclerosis and thrombosis", "volume": "", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Association of Nonalcoholic Fatty Liver Disease with Arterial Stiffness and its Metabolomic Profiling in Japanese Community-Dwellers.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "OBJECTIVES: To determine the image characteristics associated with low 18F-FDG (18F-fluorodeoxyglucose) avidity among 8-15 mm solid lung cancer. METHODS: Patients satisfying the following criteria were included: underwent surgery between January 2014 and December 2019 for lung cancer, presented 8-15 mm nodule without measurable ground glass component on preoperative CT, and underwent 18F-FDG PET before resection. Image characteristics, including air bronchogram, concave shape, pleural attachment, and background emphysema, were evaluated by two board-certified radiologists. The Mann-Whitney U test was used to compare maximum standardized uptake (SUVmax) values from 18F-FDG PET images. RESULTS: The analysis included 235 patients. The SUVmax values of lesions with air bronchogram and concave shape were significantly lower than the SUVmax values of lesions without these features (median: 1.55 vs 2.56 and 1.66 vs 2.45, both P < .001), whereas lesions arising from emphysematous lungs had significantly higher SUVmax values than lesions arising from non-emphysematous lungs (2.90 vs 1.69, P < .001). No significant differences were detected between lesions attached and not attached to pleura. The interobserver agreement was almost perfect for air bronchograms and background emphysema (kappa = 0.882 and 0.927, respectively), and 89.7% of lesions with air bronchograms and arising from non-emphysematous lungs showed SUVmax values below 2.5. CONCLUSIONS: Among 8-15 mm solid lung cancer, the presence of air bronchograms and concave shape and the absence of background emphysema were associated with low 18F-FDG accumulation. ADVANCES IN KNOWLEDGE: 18F-FDG PET can be misleading in differentiating certain type of small solid lung cancer.", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Haruto", "last_name": "Sugawara", "name": null }, { "creator_type": "author", "first_name": "Nao", "last_name": "Kikkawa", "name": null }, { "creator_type": "author", "first_name": "Kimiteru", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Hirokazu", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Sawako", "last_name": "Kaku", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Akai", "name": null }, { "creator_type": "author", "first_name": "Osamu", "last_name": "Abe", "name": null }, { "creator_type": "author", "first_name": "Shun-Ichi", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null }, { "creator_type": "author", "first_name": "Masahiko", "last_name": "Kusumoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1093/bjr/tqad048" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "38308036" } }, "mesh": [ { "descriptor": "Emphysema", "descriptor_ui": "D004646", "major_topic": true }, { "descriptor": "Fluorodeoxyglucose F18", "descriptor_ui": "D019788", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Lung", "descriptor_ui": "D008168", "major_topic": false }, { "descriptor": "Lung Neoplasms", "descriptor_ui": "D008175", "major_topic": true }, { "descriptor": "Positron Emission Tomography Computed Tomography", "descriptor_ui": "D000072078", "major_topic": false }, { "descriptor": "Positron-Emission Tomography", "descriptor_ui": "D049268", "major_topic": false }, { "descriptor": "Radiopharmaceuticals", "descriptor_ui": "D019275", "major_topic": false }, { "descriptor": "Tomography, X-Ray Computed", "descriptor_ui": "D014057", "major_topic": false } ], "publication": { "conference_name": null, "date": "2024 Feb 2", "date_precision": "day", "issue": "1154", "normalized_date": "2024-02-02", "pages": "462-468", "proceedings_title": null, "publisher": "", "title": "The British journal of radiology", "volume": "97", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Is 18F-fluorodeoxyglucose PET recommended for small lung nodules? CT findings of 18F-fluorodeoxyglucose non-avid lung cancer.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Although reactive oxygen species (ROS) are known to have harmful effects in organisms, recent studies have demonstrated expression of ROS synthases at various parts of the organisms and the controlled ROS generation, suggesting possible involvement of ROS signaling in physiological events of individuals. However, physiological roles of ROS in the CNS, including functional roles in higher brain functions or neuronal activity-dependent ROS production, remain to be elucidated. Here, we demonstrated involvement of ROS - 8-NO(2)-cGMP signaling in motor learning and synaptic plasticity in the cerebellum. In the presence of inhibitors of ROS signal or ROS synthases, cerebellar motor learning was impaired, and the stimulus inducing long-term depression (LTD), cellular basis for the motor learning, failed to induce LTD but induced long-term potentiation (LTP)-like change at cerebellar synapses. Furthermore, ROS was produced by LTD-inducing stimulus in enzyme-dependent manner, and excess administration of the antioxidant vitamin E impaired cerebellar motor learning, suggesting beneficial roles of endogenous ROS in the learning. As a downstream signal, involvement of 8-NO(2)-cGMP in motor learning and cerebellar LTD were also revealed. These findings indicate that ROS - 8-NO(2)-cGMP signal is activated by neuronal activity and is essential for cerebellum-dependent motor learning and synaptic plasticity, demonstrating involvement of the signal in physiological function of brain systems.", "classifications": [ { "id": "JPMJCR2024", "label": "JPMJCR2024", "researcher": "Motohiro Nishida", "type": "grant" }, { "id": "Akaike", "label": "Group Akaike", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Group Nishida", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Sho", "last_name": "Kakizawa", "name": null }, { "creator_type": "author", "first_name": "Tomoko", "last_name": "Arasaki", "name": null }, { "creator_type": "author", "first_name": "Ayano", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Ayami", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Yuka", "last_name": "Takino", "name": null }, { "creator_type": "author", "first_name": "Akihito", "last_name": "Ishigami", "name": null }, { "creator_type": "author", "first_name": "Takaaki", "last_name": "Akaike", "name": null }, { "creator_type": "author", "first_name": "Shuichi", "last_name": "Yanai", "name": null }, { "creator_type": "author", "first_name": "Shogo", "last_name": "Endo", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.redox.2024.103053" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "38340634" } }, "mesh": [ { "descriptor": "Cerebellum", "descriptor_ui": "D002531", "major_topic": false }, { "descriptor": "Cyclic GMP", "descriptor_ui": "D006152", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Memory, Long-Term", "descriptor_ui": "D057567", "major_topic": false }, { "descriptor": "Neuronal Plasticity", "descriptor_ui": "D009473", "major_topic": true }, { "descriptor": "Nitrogen Dioxide", "descriptor_ui": "D009585", "major_topic": true }, { "descriptor": "Reactive Oxygen Species", "descriptor_ui": "D017382", "major_topic": false } ], "publication": { "conference_name": null, "date": "2024 Feb 1", "date_precision": "day", "issue": "", "normalized_date": "2024-02-01", "pages": "103053", "proceedings_title": null, "publisher": "", "title": "Redox biology", "volume": "70", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Essential role of ROS - 8-Nitro-cGMP signaling in long-term memory of motor learning and cerebellar synaptic plasticity.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Autophagy is primarily activated by cellular stress, such as starvation or mitochondrial damage. However, stress-independent autophagy is activated by unclear mechanisms in several cell types, such as thymic epithelial cells (TECs). Here we report that the mitochondrial protein, C15ORF48, is a critical inducer of stress-independent autophagy. Mechanistically, C15ORF48 reduces the mitochondrial membrane potential and lowers intracellular ATP levels, thereby activating AMP-activated protein kinase and its downstream Unc-51-like kinase 1. Interestingly, C15ORF48-dependent induction of autophagy upregulates intracellular glutathione levels, promoting cell survival by reducing oxidative stress. Mice deficient in C15orf48 show a reduction in stress-independent autophagy in TECs, but not in typical starvation-induced autophagy in skeletal muscles. Moreover, C15orf48(-/-) mice develop autoimmunity, which is consistent with the fact that the stress-independent autophagy in TECs is crucial for the thymic self-tolerance. These results suggest that C15ORF48 induces stress-independent autophagy, thereby regulating oxidative stress and self-tolerance.", "classifications": [ { "id": "Kobayashi", "label": "Group Kobayashi", "parent": "Wakamoto", "type": "group" }, { "id": "Wakamoto", "label": "Team Wakamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yuki", "last_name": "Takakura", "name": null }, { "creator_type": "author", "first_name": "Moeka", "last_name": "Machida", "name": null }, { "creator_type": "author", "first_name": "Natsumi", "last_name": "Terada", "name": null }, { "creator_type": "author", "first_name": "Yuka", "last_name": "Katsumi", "name": null }, { "creator_type": "author", "first_name": "Seika", "last_name": "Kawamura", "name": null }, { "creator_type": "author", "first_name": "Kenta", "last_name": "Horie", "name": null }, { "creator_type": "author", "first_name": "Maki", "last_name": "Miyauchi", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Ishikawa", "name": null }, { "creator_type": "author", "first_name": "Nobuko", "last_name": "Akiyama", "name": null }, { "creator_type": "author", "first_name": "Takao", "last_name": "Seki", "name": null }, { "creator_type": "author", "first_name": "Takahisa", "last_name": "Miyao", "name": null }, { "creator_type": "author", "first_name": "Mio", "last_name": "Hayama", "name": null }, { "creator_type": "author", "first_name": "Rin", "last_name": "Endo", "name": null }, { "creator_type": "author", "first_name": "Hiroto", "last_name": "Ishii", "name": null }, { "creator_type": "author", "first_name": "Yuya", "last_name": "Maruyama", "name": null }, { "creator_type": "author", "first_name": "Naho", "last_name": "Hagiwara", "name": null }, { "creator_type": "author", "first_name": "Tetsuya J.", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Naoto", "last_name": "Yamaguchi", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Takano", "name": null }, { "creator_type": "author", "first_name": "Taishin", "last_name": "Akiyama", "name": null }, { "creator_type": "author", "first_name": "Noritaka", "last_name": "Yamaguchi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41467-024-45206-1" }, "pmcid": { "normalized": "PMC10831050" }, "pmid": { "normalized": "38296961" } }, "mesh": [ { "descriptor": "AMP-Activated Protein Kinases", "descriptor_ui": "D055372", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Autoimmunity", "descriptor_ui": "D015551", "major_topic": true }, { "descriptor": "Autophagy", "descriptor_ui": "D001343", "major_topic": false }, { "descriptor": "Epithelial Cells", "descriptor_ui": "D004847", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mitochondrial Proteins", "descriptor_ui": "D024101", "major_topic": true }, { "descriptor": "Oxidative Stress", "descriptor_ui": "D018384", "major_topic": false } ], "publication": { "conference_name": null, "date": "2024 Feb 1", "date_precision": "day", "issue": "1", "normalized_date": "2024-02-01", "pages": "953", "proceedings_title": null, "publisher": "", "title": "Nature communications", "volume": "15", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Mitochondrial protein C15ORF48 is a stress-independent inducer of autophagy that regulates oxidative stress and autoimmunity.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Label-free measurement is essential to understand the metabolism of drug molecules introduced into cells. Raman imaging is a powerful method to investigate intracellular drug molecules because it provides in situ label-free observation of introduced molecules. In this study, we propose that Raman imaging can be used not only to observe the intracellular distribution of drug molecules but also to quantitatively visualize the concentration distribution reflecting each organelle in a single living cell using the Raman band of extracellular water as an intensity standard. We dissolved poorly water-soluble all-trans-retinoic acid (ATRA) in water using a cytocompatible amphiphilic phospholipid polymer, poly[2-methacryloyloxyethyl phosphorylcholine-co-n-butyl methacrylate] (PMB) as a solubilizing reagent, introduced it into cells, and obtained the intracellular concentration distribution of ATRA. ATRA was concentrated in the cells and mainly localized to mitochondria and lipid droplets, interacting strongly with mitochondria and weakly with lipid droplets. Poorly water-soluble beta-carotene was also introduced into cells using PMB but was not concentrated intracellularly, indicating that beta-carotene does not interact specifically with intracellular molecules. We established a protocol for the solubilization and intracellular uptake of poorly water-soluble molecules using PMB and obtaining their concentration distribution using Raman microscopy.", "classifications": [ { "id": "JPMJCR2024", "label": "JPMJCR2024", "researcher": "Motohiro Nishida", "type": "grant" }, { "id": "Nakabayashi", "label": "Group Nakabayashi", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Group Nishida", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Keisuke", "last_name": "Koga", "name": null }, { "creator_type": "author", "first_name": "Shinji", "last_name": "Kajimoto", "name": null }, { "creator_type": "author", "first_name": "Yuta", "last_name": "Yoshizaki", "name": null }, { "creator_type": "author", "first_name": "Hiroaki", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Lisa", "last_name": "Kageyama", "name": null }, { "creator_type": "author", "first_name": "Tomohiro", "last_name": "Konno", "name": null }, { "creator_type": "author", "first_name": "Takakazu", "last_name": "Nakabayashi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/acs.jpcb.3c06601" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "38295808" } }, "mesh": [ { "descriptor": "beta Carotene", "descriptor_ui": "D019207", "major_topic": true }, { "descriptor": "Biological Transport", "descriptor_ui": "D001692", "major_topic": false }, { "descriptor": "Water", "descriptor_ui": "D014867", "major_topic": true } ], "publication": { "conference_name": null, "date": "2024 Jan 31", "date_precision": "day", "issue": "", "normalized_date": "2024-01-31", "pages": "", "proceedings_title": null, "publisher": "", "title": "The journal of physical chemistry. B", "volume": "", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Establishment of a Method for the Introduction of Poorly Water-Soluble Drugs in Cells and Evaluation of Intracellular Concentration Distribution Using Resonance Raman Imaging.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Proper regulation of cellular response to environmental stress is crucial for maintaining biological homeostasis and is achieved by the balance between cell death processes, such as the formation of the pyroptosis-inducing NLRP3 inflammasome, and pro-survival processes, such as stress granule (SG) assembly. However, the functional interplay between these two stress-responsive organelles remains elusive. Here, we identified DHX33, a viral RNA sensor for the NLRP3 inflammasome, as a SG component, and the SG-nucleating protein G3BP as an NLRP3 inflammasome component. We also found that a decrease in intracellular potassium (K+) concentration, a key common step in NLRP3 inflammasome activation, markedly inhibited SG assembly. Therefore, when macrophages are exposed to stress stimuli with the potential to induce both SGs and the NLRP3 inflammasome, such as cytoplasmic poly(I:C) stimulation, they preferentially form the NLRP3 inflammasome but avoid SG assembly by sequestering G3BP into the inflammasome and by inducing a reduction in intracellular K+ levels. Thus, under such conditions, DHX33 is primarily utilized as a viral RNA sensor for the inflammasome. Our data reveal the functional crosstalk between NLRP3 inflammasome-mediated pyroptosis and SG-mediated cell survival pathways, and delineate a molecular mechanism that regulates cell-fate decisions and anti-viral innate immunity under stress.", "classifications": [ { "id": "JPMJCR2022", "label": "JPMJCR2022", "researcher": "Mutsuhiro Takekawa", "type": "grant" }, { "id": "Takekawa", "label": "Group Takekawa", "parent": "Takekawa", "type": "group" }, { "id": "Takekawa", "label": "Team Takekawa", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Daisuke", "last_name": "Yoshioka", "name": null }, { "creator_type": "author", "first_name": "Takanori", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Yuji", "last_name": "Kubota", "name": null }, { "creator_type": "author", "first_name": "Mutsuhiro", "last_name": "Takekawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1093/jb/mvae009" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "38299728" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "DEAD-box RNA Helicases", "descriptor_ui": "D053487", "major_topic": false }, { "descriptor": "DNA Helicases", "descriptor_ui": "D004265", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Inflammasomes", "descriptor_ui": "D058847", "major_topic": true }, { "descriptor": "Macrophages", "descriptor_ui": "D008264", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "NLR Family, Pyrin Domain-Containing 3 Protein", "descriptor_ui": "D000071199", "major_topic": true }, { "descriptor": "Poly I-C", "descriptor_ui": "D011070", "major_topic": false }, { "descriptor": "Poly-ADP-Ribose Binding Proteins", "descriptor_ui": "D000075223", "major_topic": false }, { "descriptor": "Potassium", "descriptor_ui": "D011188", "major_topic": false }, { "descriptor": "Pyroptosis", "descriptor_ui": "D000069292", "major_topic": false }, { "descriptor": "RNA Helicases", "descriptor_ui": "D020365", "major_topic": false }, { "descriptor": "RNA Recognition Motif Proteins", "descriptor_ui": "D000067776", "major_topic": false }, { "descriptor": "Stress Granules", "descriptor_ui": "D000088162", "major_topic": true } ], "publication": { "conference_name": null, "date": "2024 Jan 31", "date_precision": "day", "issue": "", "normalized_date": "2024-01-31", "pages": "mvae009", "proceedings_title": null, "publisher": "", "title": "Journal of biochemistry", "volume": "", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Formation of the NLRP3 inflammasome inhibits stress granule assembly by multiple mechanisms.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "There are approximately 250 million people chronically infected with hepatitis B virus (HBV) worldwide. Although HBV is often integrated into the host genome and promotes hepatocarcinogenesis, vulnerability of HBV integration in liver cancer cells has not been clarified. The aim of our study is to identify vulnerability factors for HBV-associated hepatocarcinoma. Loss-of-function screening was undertaken in HepG2 and HBV-integrated HepG2.2.15 cells expressing SpCas9 using a pooled genome-wide clustered regularly interspaced short palindromic repeats (CRISPR) library. Genes whose guide RNA (gRNA) abundance significantly decreased in HepG2.2.15 cells but not in HepG2 cells were extracted using the MAGeCK algorithm. We identified four genes (BCL2L1, VPS37A, INSIG2, and CFLAR) that showed significant reductions of gRNA abundance and thus potentially involved in the vulnerability of HBV-integrated cancer cells. Among them, siRNA-mediated mRNA inhibition or CRISPR-mediated genetic deletion of INSIG2 significantly impaired cell proliferation in HepG2.2.15 cells but not in HepG2 cells. Its inhibitory effect was alleviated by cotransfection of siRNAs targeting HBV. INSIG2 inhibition suppressed the pathways related to cell cycle and DNA replication, downregulated cyclin-dependent kinase 2 (CDK2) levels, and delayed the G(1) -to-S transition in HepG2.2.15 cells. CDK2 inhibitor suppressed cell cycle progression in HepG2.2.15 cells and INSIG2 inhibition did not suppress cell proliferation in the presence of CDK2 inhibitor. In conclusion, INSIG2 inhibition induced cell cycle arrest in HBV-integrated hepatoma cells in a CDK2-dependent manner, and thus INSIG2 might be a vulnerability factor for HBV-associated liver cancer.", "classifications": [ { "id": "Yusa", "label": "Group Yusa", "parent": "Eiraku", "type": "group" }, { "id": "Eiraku", "label": "Team Eiraku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Makoto", "last_name": "Fukuoka", "name": null }, { "creator_type": "author", "first_name": "Takahiro", "last_name": "Kodama", "name": null }, { "creator_type": "author", "first_name": "Kazuhiro", "last_name": "Murai", "name": null }, { "creator_type": "author", "first_name": "Hayato", "last_name": "Hikita", "name": null }, { "creator_type": "author", "first_name": "Emi", "last_name": "Sometani", "name": null }, { "creator_type": "author", "first_name": "Jihyun", "last_name": "Sung", "name": null }, { "creator_type": "author", "first_name": "Akiyoshi", "last_name": "Shimoda", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Shigeno", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Motooka", "name": null }, { "creator_type": "author", "first_name": "Akira", "last_name": "Nishio", "name": null }, { "creator_type": "author", "first_name": "Kunimaro", "last_name": "Furuta", "name": null }, { "creator_type": "author", "first_name": "Tomohide", "last_name": "Tatsumi", "name": null }, { "creator_type": "author", "first_name": "Kosuke", "last_name": "Yusa", "name": null }, { "creator_type": "author", "first_name": "Tetsuo", "last_name": "Takehara", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/cas.16070" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "38287498" } }, "mesh": [ { "descriptor": "Carcinoma, Hepatocellular", "descriptor_ui": "D006528", "major_topic": true }, { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "DNA, Viral", "descriptor_ui": "D004279", "major_topic": false }, { "descriptor": "Hep G2 Cells", "descriptor_ui": "D056945", "major_topic": false }, { "descriptor": "Hepatitis B", "descriptor_ui": "D006509", "major_topic": true }, { "descriptor": "Hepatitis B virus", "descriptor_ui": "D006515", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Intracellular Signaling Peptides and Proteins", "descriptor_ui": "D047908", "major_topic": false }, { "descriptor": "Liver Neoplasms", "descriptor_ui": "D008113", "major_topic": true }, { "descriptor": "Membrane Proteins", "descriptor_ui": "D008565", "major_topic": false }, { "descriptor": "RNA, Guide, CRISPR-Cas Systems", "descriptor_ui": "D000094704", "major_topic": false }, { "descriptor": "RNA, Small Interfering", "descriptor_ui": "D034741", "major_topic": false }, { "descriptor": "Virus Replication", "descriptor_ui": "D014779", "major_topic": false } ], "publication": { "conference_name": null, "date": "2024 Jan 29", "date_precision": "day", "issue": "", "normalized_date": "2024-01-29", "pages": "", "proceedings_title": null, "publisher": "", "title": "Cancer science", "volume": "", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Genome-wide loss-of-function genetic screen identifies INSIG2 as the vulnerability of hepatitis B virus-integrated hepatoma cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "DNA underwinding (untwisting) is a crucial step in transcriptional activation. DNA underwinding occurs between the site where torque is generated by RNA polymerase (RNAP) and the site where the axial rotation of DNA is constrained. However, what constrains DNA axial rotation in the nucleus is yet unknown. Here, we show that the anchorage to the nuclear protein condensates constrains DNA axial rotation for DNA underwinding in the nucleolus. In situ super-resolution imaging of underwound DNA reveal that underwound DNA accumulates in the nucleolus, a nuclear condensate with a core-shell structure. Specifically, underwound DNA is distributed in the nucleolar core owing to RNA polymerase I (RNAPI) activities. Furthermore, underwound DNA in the core decreases when nucleolar shell components are prevented from binding to their recognition structure, G-quadruplex (G4). Taken together, these results suggest that the nucleolar shell provides anchoring sites that constrain DNA axial rotation for RNAPI-driven DNA underwinding in the core. Our findings will contribute to understanding how nuclear protein condensates make up constraints for the site-specific regulation of DNA underwinding and transcription.", "classifications": [ { "id": "JPMJCR2023", "label": "JPMJCR2023", "researcher": "Fumiko Toyoshima", "type": "grant" }, { "id": "Maki", "label": "Group Maki", "parent": "Toyoshima", "type": "group" }, { "id": "Toyoshima", "label": "Group Toyoshima", "parent": "Toyoshima", "type": "group" }, { "id": "Toyoshima", "label": "Team Toyoshima", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Jumpei", "last_name": "Fukute", "name": null }, { "creator_type": "author", "first_name": "Koichiro", "last_name": "Maki", "name": null }, { "creator_type": "author", "first_name": "Taiji", "last_name": "Adachi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s42003-023-05750-w" }, "pmcid": { "normalized": "PMC10805735" }, "pmid": { "normalized": "38263258" } }, "mesh": [ { "descriptor": "DNA", "descriptor_ui": "D004247", "major_topic": true }, { "descriptor": "G-Quadruplexes", "descriptor_ui": "D054856", "major_topic": true }, { "descriptor": "Nuclear Proteins", "descriptor_ui": "D009687", "major_topic": false }, { "descriptor": "Recognition, Psychology", "descriptor_ui": "D021641", "major_topic": false }, { "descriptor": "Rotation", "descriptor_ui": "D012399", "major_topic": false } ], "publication": { "conference_name": null, "date": "2024 Jan 23", "date_precision": "day", "issue": "1", "normalized_date": "2024-01-23", "pages": "83", "proceedings_title": null, "publisher": "", "title": "Communications biology", "volume": "7", "year": 2024 }, "ssbd": { "database": [ "ssbd-database-000394" ], "repository": [ "ssbd-repos-000394" ] }, "title": "The nucleolar shell provides anchoring sites for DNA untwisting.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Studies examining long-term longitudinal metabolomic data and their reliability in large-scale populations are limited. Therefore, we aimed to evaluate the reliability of repeated measurements of plasma metabolites in a prospective cohort setting and to explore intra-individual concentration changes at three time points over a 6-year period. The study participants included 2999 individuals (1317 men and 1682 women) from the Tsuruoka Metabolomics Cohort Study, who participated in all three surveys-at baseline, 3 years, and 6 years. In each survey, 94 plasma metabolites were quantified for each individual and quality control (QC) sample. The coefficients of variation of QC, intraclass correlation coefficients, and change rates of QC were calculated for each metabolite, and their reliability was classified into three categories: excellent, fair to good, and poor. Seventy-six percent (71/94) of metabolites were classified as fair to good or better. Of the 39 metabolites grouped as excellent, 29 (74%) in men and 26 (67%) in women showed significant intra-individual changes over 6 years. Overall, our study demonstrated a high degree of reliability for repeated metabolome measurements. Many highly reliable metabolites showed significant changes over the 6-year period, suggesting that repeated longitudinal metabolome measurements are useful for epidemiological studies.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Atsuko", "last_name": "Miyake", "name": null }, { "creator_type": "author", "first_name": "Sei", "last_name": "Harada", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Sugiyama", "name": null }, { "creator_type": "author", "first_name": "Minako", "last_name": "Matsumoto", "name": null }, { "creator_type": "author", "first_name": "Aya", "last_name": "Hirata", "name": null }, { "creator_type": "author", "first_name": "Naoko", "last_name": "Miyagawa", "name": null }, { "creator_type": "author", "first_name": "Ryota", "last_name": "Toki", "name": null }, { "creator_type": "author", "first_name": "Shun", "last_name": "Edagawa", "name": null }, { "creator_type": "author", "first_name": "Kazuyo", "last_name": "Kuwabara", "name": null }, { "creator_type": "author", "first_name": "Tomonori", "last_name": "Okamura", "name": null }, { "creator_type": "author", "first_name": "Asako", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Kaori", "last_name": "Amano", "name": null }, { "creator_type": "author", "first_name": "Akiyoshi", "last_name": "Hirayama", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Sugimoto", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Masaru", "last_name": "Tomita", "name": null }, { "creator_type": "author", "first_name": "Kazuharu", "last_name": "Arakawa", "name": null }, { "creator_type": "author", "first_name": "Toru", "last_name": "Takebayashi", "name": null }, { "creator_type": "author", "first_name": "Miho", "last_name": "Iida", "name": null } ], "identifiers": { "doi": { "normalized": "10.3390/metabo14010077" }, "pmcid": { "normalized": "PMC10819202" }, "pmid": { "normalized": "38276312" } }, "mesh": [], "publication": { "conference_name": null, "date": "2024 Jan 22", "date_precision": "day", "issue": "1", "normalized_date": "2024-01-22", "pages": "", "proceedings_title": null, "publisher": "", "title": "Metabolites", "volume": "14", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Reliability of Time-Series Plasma Metabolome Data over 6 Years in a Large-Scale Cohort Study.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Blood vessels show various COVID-19-related conditions including thrombosis and cytokine propagation. Existing in vitro blood vessel models cannot represent the consequent changes in the vascular structure or determine the initial infection site, making it difficult to evaluate how epithelial and endothelial tissues are damaged. Here, we developed a microphysiological system (MPS) that co-culture the bronchial organoids and the vascular bed to analyze infection site and interactions. In this system, virus-infected organoids caused damage in vascular structure. However, vasculature was not damaged or infected when the virus was directly introduced to vascular bed. The knockout of interferon-related genes and inhibition of the JAK/STAT pathway reduced the vascular damage, indicating the protective effect of interferon response suppression. The results demonstrate selective infection of bronchial epithelial cells and vascular damage by cytokines and also indicate the applicability of MPS to investigate how the infection influences vascular structure and functions.", "classifications": [ { "id": "Yamamoto", "label": "Group Yamamoto", "parent": "Toyoshima", "type": "group" }, { "id": "Toyoshima", "label": "Team Toyoshima", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Kazuya", "last_name": "Fujimoto", "name": null }, { "creator_type": "author", "first_name": "Yoshikazu", "last_name": "Kameda", "name": null }, { "creator_type": "author", "first_name": "Yuta", "last_name": "Nagano", "name": null }, { "creator_type": "author", "first_name": "Sayaka", "last_name": "Deguchi", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Rafal P.", "last_name": "Krol", "name": null }, { "creator_type": "author", "first_name": "Peter", "last_name": "Gee", "name": null }, { "creator_type": "author", "first_name": "Yasufumi", "last_name": "Matsumura", "name": null }, { "creator_type": "author", "first_name": "Toru", "last_name": "Okamoto", "name": null }, { "creator_type": "author", "first_name": "Miki", "last_name": "Nagao", "name": null }, { "creator_type": "author", "first_name": "Kazuo", "last_name": "Takayama", "name": null }, { "creator_type": "author", "first_name": "Ryuji", "last_name": "Yokokawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1039/d3lc00768e" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "38252025" } }, "mesh": [ { "descriptor": "Bronchi", "descriptor_ui": "D001980", "major_topic": true }, { "descriptor": "COVID-19", "descriptor_ui": "D000086382", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Interferon Type I", "descriptor_ui": "D007370", "major_topic": true }, { "descriptor": "Microphysiological Systems", "descriptor_ui": "D000094182", "major_topic": false }, { "descriptor": "Organoids", "descriptor_ui": "D009940", "major_topic": true }, { "descriptor": "SARS-CoV-2", "descriptor_ui": "D000086402", "major_topic": true } ], "publication": { "conference_name": null, "date": "2024 Jan 22", "date_precision": "day", "issue": "", "normalized_date": "2024-01-22", "pages": "", "proceedings_title": null, "publisher": "", "title": "Lab on a chip", "volume": "", "year": 2024 }, "ssbd": { "database": [ "ssbd-database-000393" ], "repository": [ "ssbd-repos-000393" ] }, "title": "SARS-CoV-2-induced disruption of a vascular bed in a microphysiological system caused by type-I interferon from bronchial organoids.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: Depression and anxiety are among the most prevalent mental health issues experienced worldwide. However, whereas cross-cultural studies utilize psychometrically valid and reliable scales, fewer can meaningfully compare these conditions across different groups. To address this gap, the current study aimed to psychometrically assess the Brief Symptomatology Index (BSI) in 42 countries. METHODS: Using data from the International Sex Survey (N = 82,243; M(age) = 32.39; SD(age) = 12.52; women: n = 46,874; 57 %), we examined the reliability of depression and anxiety symptom scores of the BSI-18, as well as evaluated evidence of construct, invariance, and criterion-related validity in predicting clinically relevant variables across countries, languages, genders, and sexual orientations. RESULTS: Results corroborated an invariant, two-factor structure across all groups tested, exhibiting excellent reliability estimates for both subscales. The 'caseness' criterion effectively discriminated among those at low and high risk of depression and anxiety, yielding differential effects on the clinical criteria examined. LIMITATIONS: The predictive validation was not made against a clinical diagnosis, and the full BSI-18 scale was not examined (excluding the somatization sub-dimension), limiting the validation scope of the BSI-18. Finally, the study was conducted online, mainly by advertisements through social media, ultimately skewing our sample towards women, younger, and highly educated populations. CONCLUSIONS: The results support that the BSI-12 is a valid and reliable assessment tool for assessing depression and anxiety symptoms across countries, languages, genders, and sexual orientations. Further, its caseness criterion can discriminate well between participants at high and low risk of depression and anxiety.", "classifications": [ { "id": "Fujiwara", "label": "Group Fujiwara", "parent": "Fujiwara", "type": "group" }, { "id": "Fujiwara", "label": "Team Fujiwara", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Gonzalo R.", "last_name": "Quintana", "name": null }, { "creator_type": "author", "first_name": "Fernando P.", "last_name": "Ponce", "name": null }, { "creator_type": "author", "first_name": "Javier I.", "last_name": "Escudero-Pasten", "name": null }, { "creator_type": "author", "first_name": "Juan F.", "last_name": "Santibanez-Palma", "name": null }, { "creator_type": "author", "first_name": "Lena", "last_name": "Nagy", "name": null }, { "creator_type": "author", "first_name": "Monika", "last_name": "Koos", "name": null }, { "creator_type": "author", "first_name": "Shane W.", "last_name": "Kraus", "name": null }, { "creator_type": "author", "first_name": "Zsolt", "last_name": "Demetrovics", "name": null }, { "creator_type": "author", "first_name": "Marc N.", "last_name": "Potenza", "name": null }, { "creator_type": "author", "first_name": "Rafael", "last_name": "Ballester-Arnal", "name": null }, { "creator_type": "author", "first_name": "Dominik", "last_name": "Batthyany", "name": null }, { "creator_type": "author", "first_name": "Sophie", "last_name": "Bergeron", "name": null }, { "creator_type": "author", "first_name": "Joel", "last_name": "Billieux", "name": null }, { "creator_type": "author", "first_name": "Peer", "last_name": "Briken", "name": null }, { "creator_type": "author", "first_name": "Julius", "last_name": "Burkauskas", "name": null }, { "creator_type": "author", "first_name": "Georgina", "last_name": "Cardenas-Lopez", "name": null }, { "creator_type": "author", "first_name": "Joana", "last_name": "Carvalho", "name": null }, { "creator_type": "author", "first_name": "Jesus", "last_name": "Castro-Calvo", "name": null }, { "creator_type": "author", "first_name": "Lijun", "last_name": "Chen", "name": null }, { "creator_type": "author", "first_name": "Giacomo", "last_name": "Ciocca", "name": null }, { "creator_type": "author", "first_name": "Ornella", "last_name": "Corazza", "name": null }, { "creator_type": "author", "first_name": "Rita I.", "last_name": "Csako", "name": null }, { "creator_type": "author", "first_name": "David P.", "last_name": "Fernandez", "name": null }, { "creator_type": "author", "first_name": "Elaine F.", "last_name": "Fernandez", "name": null }, { "creator_type": "author", "first_name": "Hironobu", "last_name": "Fujiwara", "name": null }, { "creator_type": "author", "first_name": "Johannes", "last_name": "Fuss", "name": null }, { "creator_type": "author", "first_name": "Roman", "last_name": "Gabrhelik", "name": null }, { "creator_type": "author", "first_name": "Ateret", "last_name": "Gewirtz-Meydan", "name": null }, { "creator_type": "author", "first_name": "Biljana", "last_name": "Gjoneska", "name": null }, { "creator_type": "author", "first_name": "Mateusz", "last_name": "Gola", "name": null }, { "creator_type": "author", "first_name": "Joshua B.", "last_name": "Grubbs", "name": null }, { "creator_type": "author", "first_name": "Hashim T.", "last_name": "Hashim", "name": null }, { "creator_type": "author", "first_name": "Md Saiful", "last_name": "Islam", "name": null }, { "creator_type": "author", "first_name": "Mustafa", "last_name": "Ismail", "name": null }, { "creator_type": "author", "first_name": "Martha C.", "last_name": "Jimenez-Martinez", "name": null }, { "creator_type": "author", "first_name": "Tanja", "last_name": "Jurin", "name": null }, { "creator_type": "author", "first_name": "Ondrej", "last_name": "Kalina", "name": null }, { "creator_type": "author", "first_name": "Verena", "last_name": "Klein", "name": null }, { "creator_type": "author", "first_name": "Andras", "last_name": "Kolto", "name": null }, { "creator_type": "author", "first_name": "Chih-Ting", "last_name": "Lee", "name": null }, { "creator_type": "author", "first_name": "Sang-Kyu", "last_name": "Lee", "name": null }, { "creator_type": "author", "first_name": "Karol", "last_name": "Lewczuk", "name": null }, { "creator_type": "author", "first_name": "Chung-Ying", "last_name": "Lin", "name": null }, { "creator_type": "author", "first_name": "Christine", "last_name": "Lochner", "name": null }, { "creator_type": "author", "first_name": "Silvia", "last_name": "Lopez-Alvarado", "name": null }, { "creator_type": "author", "first_name": "Katerina", "last_name": "Lukavska", "name": null }, { "creator_type": "author", "first_name": "Percy", "last_name": "Mayta-Tristan", "name": null }, { "creator_type": "author", "first_name": "Dan J.", "last_name": "Miller", "name": null }, { "creator_type": "author", "first_name": "Olga", "last_name": "Orosova", "name": null }, { "creator_type": "author", "first_name": "Gabor", "last_name": "Orosz", "name": null }, { "creator_type": "author", "first_name": "Gabriel C.", "last_name": "Quintero Garzola", "name": null }, { "creator_type": "author", "first_name": "Jano", "last_name": "Ramos-Diaz", "name": null }, { "creator_type": "author", "first_name": "Kevin", "last_name": "Rigaud", "name": null }, { "creator_type": "author", "first_name": "Ann", "last_name": "Rousseau", "name": null }, { "creator_type": "author", "first_name": "Marco De Tubino", "last_name": "Scanavino", "name": null }, { "creator_type": "author", "first_name": "Marion K.", "last_name": "Schulmeyer", "name": null }, { "creator_type": "author", "first_name": "Pratap", "last_name": "Sharan", "name": null }, { "creator_type": "author", "first_name": "Mami", "last_name": "Shibata", "name": null }, { "creator_type": "author", "first_name": "Sheikh", "last_name": "Shoib", "name": null }, { "creator_type": "author", "first_name": "Vera", "last_name": "Sigre-Leiros", "name": null }, { "creator_type": "author", "first_name": "Luke", "last_name": "Sniewski", "name": null }, { "creator_type": "author", "first_name": "Ognen", "last_name": "Spasovski", "name": null }, { "creator_type": "author", "first_name": "Vesta", "last_name": "Steibliene", "name": null }, { "creator_type": "author", "first_name": "Dan J.", "last_name": "Stein", "name": null }, { "creator_type": "author", "first_name": "Berk C.", "last_name": "Unsal", "name": null }, { "creator_type": "author", "first_name": "Marie-Pier", "last_name": "Vaillancourt-Morel", "name": null }, { "creator_type": "author", "first_name": "Marie Claire", "last_name": "Van Hout", "name": null }, { "creator_type": "author", "first_name": "Beata", "last_name": "Bothe", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.jad.2024.01.127" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "38244805" } }, "mesh": [ { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Anxiety", "descriptor_ui": "D001007", "major_topic": false }, { "descriptor": "Child", "descriptor_ui": "D002648", "major_topic": false }, { "descriptor": "Cross-Cultural Comparison", "descriptor_ui": "D003431", "major_topic": true }, { "descriptor": "Depression", "descriptor_ui": "D003863", "major_topic": true }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Psychometrics", "descriptor_ui": "D011594", "major_topic": false }, { "descriptor": "Reproducibility of Results", "descriptor_ui": "D015203", "major_topic": false }, { "descriptor": "Surveys and Questionnaires", "descriptor_ui": "D011795", "major_topic": false } ], "publication": { "conference_name": null, "date": "2024 Jan 18", "date_precision": "day", "issue": "", "normalized_date": "2024-01-18", "pages": "S0165-0327(24)00144-7", "proceedings_title": null, "publisher": "", "title": "Journal of affective disorders", "volume": "", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Cross-cultural validation and measurement invariance of anxiety and depression symptoms: A study of the Brief Symptom Inventory (BSI) in 42 countries.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The development of artificial spider silk with properties similar to native silk has been a challenging task in materials science. In this study, we use a microfluidic device to create continuous fibers based on recombinant MaSp2 spidroin. The strategy incorporates ion-induced liquid-liquid phase separation, pH-driven fibrillation, and shear-dependent induction of beta-sheet formation. We find that a threshold shear stress of approximately 72 Pa is required for fiber formation, and that beta-sheet formation is dependent on the presence of polyalanine blocks in the repetitive sequence. The MaSp2 fiber formed has a beta-sheet content (29.2%) comparable to that of native dragline with a shear stress requirement of 111 Pa. Interestingly, the polyalanine blocks have limited influence on the occurrence of liquid-liquid phase separation and hierarchical structure. These results offer insights into the shear-induced crystallization and sequence-structure relationship of spider silk and have significant implications for the rational design of artificially spun fibers.", "classifications": [ { "id": "Shintaku", "label": "Group Shintaku", "parent": "Shintaku", "type": "group" }, { "id": "Shintaku", "label": "Team Shintaku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Jianming", "last_name": "Chen", "name": null }, { "creator_type": "author", "first_name": "Arata", "last_name": "Tsuchida", "name": null }, { "creator_type": "author", "first_name": "Ali D.", "last_name": "Malay", "name": null }, { "creator_type": "author", "first_name": "Kousuke", "last_name": "Tsuchiya", "name": null }, { "creator_type": "author", "first_name": "Hiroyasu", "last_name": "Masunaga", "name": null }, { "creator_type": "author", "first_name": "Yui", "last_name": "Tsuji", "name": null }, { "creator_type": "author", "first_name": "Mako", "last_name": "Kuzumoto", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Urayama", "name": null }, { "creator_type": "author", "first_name": "Hirofumi", "last_name": "Shintaku", "name": null }, { "creator_type": "author", "first_name": "Keiji", "last_name": "Numata", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41467-024-44733-1" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "38225234" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Fibroins", "descriptor_ui": "D005349", "major_topic": true }, { "descriptor": "Microfluidics", "descriptor_ui": "D044085", "major_topic": false }, { "descriptor": "Repetitive Sequences, Nucleic Acid", "descriptor_ui": "D012091", "major_topic": false }, { "descriptor": "Silk", "descriptor_ui": "D047011", "major_topic": false }, { "descriptor": "Spiders", "descriptor_ui": "D013112", "major_topic": true } ], "publication": { "conference_name": null, "date": "2024 Jan 15", "date_precision": "day", "issue": "1", "normalized_date": "2024-01-15", "pages": "527", "proceedings_title": null, "publisher": "", "title": "Nature communications", "volume": "15", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Replicating shear-mediated self-assembly of spider silk through microfluidics.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Accumulating evidence suggests that cellular heterogeneity in organs and cell-cell and tissue-tissue interactions are crucial for maintaining physical homeostasis and disease progression. Endocrine organs also exhibit cellular heterogeneity and comprise multiple cell types. For instance, the pituitary gland comprises five types of pituitary hormone-producing cells as well as non-hormone-producing supporting cells, such as fibroblasts, endothelial cells, and folliculostellate cells. However, the functional roles of the interactions between hormone-producing and non-producing cells in the pituitary gland remain incompletely understood. Over the past decade, emerging technologies such as single-cell and spatial transcriptomics have provided excellent tools for studying cellular heterogeneity and their interactions; however, the application of these technologies in endocrine research remains limited. This review provides an overview of these technologies and discusses their strengths and limitations. Additionally, we also summarize the potential future applications of single-cell and spatial transcriptomics in the study of endocrine organs and their disorders.", "classifications": [ { "id": "Yamamoto", "label": "Group Yamamoto", "parent": "Toyoshima", "type": "group" }, { "id": "Toyoshima", "label": "Team Toyoshima", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Ryusaku", "last_name": "Matsumoto", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Yamamoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1507/endocrj.ej23-0457" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "38220200" } }, "mesh": [ { "descriptor": "Endothelial Cells", "descriptor_ui": "D042783", "major_topic": true }, { "descriptor": "Gene Expression Profiling", "descriptor_ui": "D020869", "major_topic": false }, { "descriptor": "Pituitary Gland", "descriptor_ui": "D010902", "major_topic": true }, { "descriptor": "Transcriptome", "descriptor_ui": "D059467", "major_topic": false } ], "publication": { "conference_name": null, "date": "2024 Jan 13", "date_precision": "day", "issue": "", "normalized_date": "2024-01-13", "pages": "", "proceedings_title": null, "publisher": "", "title": "Endocrine journal", "volume": "", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Single-cell and spatial transcriptomics in endocrine research.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The gut microbiota is closely associated with human health and is greatly impacted by the host diet. Bacteria such as Escherichia coli live in the gut all throughout the life of a human host and adapt to the intestinal environment. Adaptive mutations in E. coli are reported to enhance fitness in the mammalian intestine, but to what extent is still poorly known. It is also unknown whether the host diet affects what genes are mutated and to what extent fitness is affected. This study suggests that genetic mutations in the E. coli K-12 strain are selected in response to the intestinal environment and facilitate efficient utilization of abundant nutrients in the germ-free mouse intestine. Our study provides a better understanding of these intestinal adaptation mechanisms of gut microbes.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Tomoya", "last_name": "Tsukimi", "name": null }, { "creator_type": "author", "first_name": "Nozomu", "last_name": "Obana", "name": null }, { "creator_type": "author", "first_name": "Suguru", "last_name": "Shigemori", "name": null }, { "creator_type": "author", "first_name": "Kazuharu", "last_name": "Arakawa", "name": null }, { "creator_type": "author", "first_name": "Eiji", "last_name": "Miyauchi", "name": null }, { "creator_type": "author", "first_name": "Jiayue", "last_name": "Yang", "name": null }, { "creator_type": "author", "first_name": "Isaiah", "last_name": "Song", "name": null }, { "creator_type": "author", "first_name": "Yujin", "last_name": "Ashino", "name": null }, { "creator_type": "author", "first_name": "Masataka", "last_name": "Wakayama", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Masaru", "last_name": "Tomita", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Ohno", "name": null }, { "creator_type": "author", "first_name": "Hirotada", "last_name": "Mori", "name": null }, { "creator_type": "author", "first_name": "Shinji", "last_name": "Fukuda", "name": null } ], "identifiers": { "doi": { "normalized": "10.1128/msystems.01123-23" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "38205998" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Diet", "descriptor_ui": "D004032", "major_topic": false }, { "descriptor": "Ecosystem", "descriptor_ui": "D017753", "major_topic": true }, { "descriptor": "Escherichia coli", "descriptor_ui": "D004926", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Intestines", "descriptor_ui": "D007422", "major_topic": false }, { "descriptor": "Mammals", "descriptor_ui": "D008322", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": false } ], "publication": { "conference_name": null, "date": "2024 Jan 11", "date_precision": "day", "issue": "", "normalized_date": "2024-01-11", "pages": "e0112323", "proceedings_title": null, "publisher": "", "title": "mSystems", "volume": "", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Genetic mutation in Escherichia coli genome during adaptation to the murine intestine is optimized for the host diet.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The Tsuruoka Metabolomics Cohort Study (TMCS) is an ongoing population-based cohort study being conducted in the rural area of Yamagata Prefecture, Japan. This study aimed to enhance the precision prevention of multi-factorial, complex diseases, including non-communicable and aging-associated diseases, by improving risk stratification and prediction measures. At baseline, 11,002 participants aged 35-74 years were recruited in Tsuruoka City, Yamagata Prefecture, Japan, between 2012 and 2015, with an ongoing follow-up survey. Participants underwent various measurements, examinations, tests, and questionnaires on their health, lifestyle, and social factors. This study used an integrative approach with deep molecular profiling to identify potential biomarkers linked to phenotypes that underpin disease pathophysiology and provide better mechanistic insights into social health determinants. The TMCS incorporates multi-omics data, including genetic and metabolomic analyses of 10,933 participants and comprehensive data collection ranging from physical, psychological, behavioral, and social to biological data. The metabolome is used as a phenotypic probe because it is sensitive to changes in physiological and external conditions. The TMCS focuses on collecting outcomes for cardiovascular disease, cancer incidence and mortality, disability, functional decline due to aging and disease sequelae, and the variation in health status within the body represented by omics analysis that lies between exposure and disease. It contains several sub-studies on aging, heated tobacco products, and women's health. This study is notable for its robust design, high participation rate (89%), and long-term repeated surveys. Moreover, it contributes to precision prevention in Japan and East Asia as a well-established multi-omics platform.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Sei", "last_name": "Harada", "name": null }, { "creator_type": "author", "first_name": "Miho", "last_name": "Iida", "name": null }, { "creator_type": "author", "first_name": "Naoko", "last_name": "Miyagawa", "name": null }, { "creator_type": "author", "first_name": "Aya", "last_name": "Hirata", "name": null }, { "creator_type": "author", "first_name": "Kazuyo", "last_name": "Kuwabara", "name": null }, { "creator_type": "author", "first_name": "Minako", "last_name": "Matsumoto", "name": null }, { "creator_type": "author", "first_name": "Tomonori", "last_name": "Okamura", "name": null }, { "creator_type": "author", "first_name": "Shun", "last_name": "Edagawa", "name": null }, { "creator_type": "author", "first_name": "Yoko", "last_name": "Kawada", "name": null }, { "creator_type": "author", "first_name": "Atsuko", "last_name": "Miyake", "name": null }, { "creator_type": "author", "first_name": "Ryota", "last_name": "Toki", "name": null }, { "creator_type": "author", "first_name": "Miki", "last_name": "Akiyama", "name": null }, { "creator_type": "author", "first_name": "Atsuki", "last_name": "Kawai", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Sugiyama", "name": null }, { "creator_type": "author", "first_name": "Yasunori", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Ryo", "last_name": "Takemura", "name": null }, { "creator_type": "author", "first_name": "Kota", "last_name": "Fukai", "name": null }, { "creator_type": "author", "first_name": "Yoshiki", "last_name": "Ishibashi", "name": null }, { "creator_type": "author", "first_name": "Suzuka", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Ayako", "last_name": "Kurihara", "name": null }, { "creator_type": "author", "first_name": "Mizuki", "last_name": "Sata", "name": null }, { "creator_type": "author", "first_name": "Takuma", "last_name": "Shibuki", "name": null }, { "creator_type": "author", "first_name": "Ayano", "last_name": "Takeuchi", "name": null }, { "creator_type": "author", "first_name": "Shun", "last_name": "Kohsaka", "name": null }, { "creator_type": "author", "first_name": "Mitsuaki", "last_name": "Sawano", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Shoji", "name": null }, { "creator_type": "author", "first_name": "Yoshikane", "last_name": "Izawa", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Katsumata", "name": null }, { "creator_type": "author", "first_name": "Koichi", "last_name": "Oki", "name": null }, { "creator_type": "author", "first_name": "Shinichi", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Tsubasa", "last_name": "Takizawa", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Maruya", "name": null }, { "creator_type": "author", "first_name": "Yuji", "last_name": "Nishiwaki", "name": null }, { "creator_type": "author", "first_name": "Ryo", "last_name": "Kawasaki", "name": null }, { "creator_type": "author", "first_name": "Akiyoshi", "last_name": "Hirayama", "name": null }, { "creator_type": "author", "first_name": "Takamasa", "last_name": "Ishikawa", "name": null }, { "creator_type": "author", "first_name": "Rintaro", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Asako", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Sugimoto", "name": null }, { "creator_type": "author", "first_name": "Masaru", "last_name": "Tomita", "name": null }, { "creator_type": "author", "first_name": "Shohei", "last_name": "Komaki", "name": null }, { "creator_type": "author", "first_name": "Hideki", "last_name": "Ohmomo", "name": null }, { "creator_type": "author", "first_name": "Kanako", "last_name": "Ono", "name": null }, { "creator_type": "author", "first_name": "Yayoi", "last_name": "Otsuka-Yamasaki", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Shimizu", "name": null }, { "creator_type": "author", "first_name": "Yoichi", "last_name": "Sutoh", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Hozawa", "name": null }, { "creator_type": "author", "first_name": "Kengo", "last_name": "Kinoshita", "name": null }, { "creator_type": "author", "first_name": "Seizo", "last_name": "Koshiba", "name": null }, { "creator_type": "author", "first_name": "Kazuki", "last_name": "Kumada", "name": null }, { "creator_type": "author", "first_name": "Soichi", "last_name": "Ogishima", "name": null }, { "creator_type": "author", "first_name": "Mika", "last_name": "Sakurai-Yageta", "name": null }, { "creator_type": "author", "first_name": "Gen", "last_name": "Tamiya", "name": null }, { "creator_type": "author", "first_name": "Toru", "last_name": "Takebayashi", "name": null } ], "identifiers": { "doi": { "normalized": "10.2188/jea.je20230192" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "38191178" } }, "mesh": [ { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Biomarkers", "descriptor_ui": "D015415", "major_topic": false }, { "descriptor": "Cohort Studies", "descriptor_ui": "D015331", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Japan", "descriptor_ui": "D007564", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Metabolomics", "descriptor_ui": "D055432", "major_topic": true }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false } ], "publication": { "conference_name": null, "date": "2024 Jan 6", "date_precision": "day", "issue": "", "normalized_date": "2024-01-06", "pages": "", "proceedings_title": null, "publisher": "", "title": "Journal of epidemiology", "volume": "", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Study Profile of the Tsuruoka Metabolomics Cohort Study (TMCS).", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "OBJECTIVE: We analyzed adult ADHD symptoms in a cross-cultural context, including investigating the occurrence and potential correlates of adult ADHD and psychometric examination of the Adult ADHD Self-Report Scale (ASRS) Screener. METHOD: Our analysis is based on a large-scale research project involving 42 countries (International Sex Survey, N=72,627, 57% women, Mage=32.84; SDage=12.57). RESULTS: The ASRS Screener demonstrated good reliability and validity, along with partial invariance across different languages, countries, and genders. The occurrence of being at risk for adult ADHD was relatively high (21.4% for women, 18.1% for men). The highest scores were obtained in the US, Canada, and other English-speaking Western countries, with significantly lower scores among East Asian and non-English-speaking European countries. Moreover, ADHD symptom severity and occurrence were especially high among gender-diverse individuals. Significant associations between adult ADHD symptoms and age, mental and sexual health, and socioeconomic status were observed. CONCLUSIONS: Present results show significant cross-cultural variability in adult ADHD occurrence as well as highlight important factors related to adult ADHD. Moreover, the importance of further research on adult ADHD in previously understudied populations (non-Western countries) and minority groups (gender-diverse individuals) is stressed. Lastly, the present analysis is consistent with previous evidence showing low specificity of adult ADHD screening instruments and contributes to the current discussion on accurate adult ADHD screening and diagnosis.", "classifications": [ { "id": "Fujiwara", "label": "Group Fujiwara", "parent": "Fujiwara", "type": "group" }, { "id": "Fujiwara", "label": "Team Fujiwara", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Karol", "last_name": "Lewczuk", "name": null }, { "creator_type": "author", "first_name": "Przemyslaw", "last_name": "Marcowski", "name": null }, { "creator_type": "author", "first_name": "Magdalena", "last_name": "Wizla", "name": null }, { "creator_type": "author", "first_name": "Mateusz", "last_name": "Gola", "name": null }, { "creator_type": "author", "first_name": "Lena", "last_name": "Nagy", "name": null }, { "creator_type": "author", "first_name": "Monika", "last_name": "Koos", "name": null }, { "creator_type": "author", "first_name": "Shane W.", "last_name": "Kraus", "name": null }, { "creator_type": "author", "first_name": "Zsolt", "last_name": "Demetrovics", "name": null }, { "creator_type": "author", "first_name": "Marc N.", "last_name": "Potenza", "name": null }, { "creator_type": "author", "first_name": "Rafael", "last_name": "Ballester-Arnal", "name": null }, { "creator_type": "author", "first_name": "Dominik", "last_name": "Batthyany", "name": null }, { "creator_type": "author", "first_name": "Sophie", "last_name": "Bergeron", "name": null }, { "creator_type": "author", "first_name": "Joel", "last_name": "Billieux", "name": null }, { "creator_type": "author", "first_name": "Peer", "last_name": "Briken", "name": null }, { "creator_type": "author", "first_name": "Julius", "last_name": "Burkauskas", "name": null }, { "creator_type": "author", "first_name": "Georgina", "last_name": "Cardenas-Lopez", "name": null }, { "creator_type": "author", "first_name": "Joana", "last_name": "Carvalho", "name": null }, { "creator_type": "author", "first_name": "Jesus", "last_name": "Castro-Calvo", "name": null }, { "creator_type": "author", "first_name": "Lijun", "last_name": "Chen", "name": null }, { "creator_type": "author", "first_name": "Giacomo", "last_name": "Ciocca", "name": null }, { "creator_type": "author", "first_name": "Ornella", "last_name": "Corazza", "name": null }, { "creator_type": "author", "first_name": "Rita I.", "last_name": "Csako", "name": null }, { "creator_type": "author", "first_name": "David P.", "last_name": "Fernandez", "name": null }, { "creator_type": "author", "first_name": "Hironobu", "last_name": "Fujiwara", "name": null }, { "creator_type": "author", "first_name": "Elaine F.", "last_name": "Fernandez", "name": null }, { "creator_type": "author", "first_name": "Johannes", "last_name": "Fuss", "name": null }, { "creator_type": "author", "first_name": "Roman", "last_name": "Gabrhelik", "name": null }, { "creator_type": "author", "first_name": "Ateret", "last_name": "Gewirtz-Meydan", "name": null }, { "creator_type": "author", "first_name": "Biljana", "last_name": "Gjoneska", "name": null }, { "creator_type": "author", "first_name": "Joshua B.", "last_name": "Grubbs", "name": null }, { "creator_type": "author", "first_name": "Hashim T.", "last_name": "Hashim", "name": null }, { "creator_type": "author", "first_name": "Md Saiful", "last_name": "Islam", "name": null }, { "creator_type": "author", "first_name": "Mustafa", "last_name": "Ismail", "name": null }, { "creator_type": "author", "first_name": "Martha C.", "last_name": "Jimenez-Martinez", "name": null }, { "creator_type": "author", "first_name": "Tanja", "last_name": "Jurin", "name": null }, { "creator_type": "author", "first_name": "Ondrej", "last_name": "Kalina", "name": null }, { "creator_type": "author", "first_name": "Verena", "last_name": "Klein", "name": null }, { "creator_type": "author", "first_name": "Andras", "last_name": "Kolto", "name": null }, { "creator_type": "author", "first_name": "Sang-Kyu", "last_name": "Lee", "name": null }, { "creator_type": "author", "first_name": "Chung-Ying", "last_name": "Lin", "name": null }, { "creator_type": "author", "first_name": "Yi-Ching", "last_name": "Lin", "name": null }, { "creator_type": "author", "first_name": "Christine", "last_name": "Lochner", "name": null }, { "creator_type": "author", "first_name": "Silvia", "last_name": "Lopez-Alvarado", "name": null }, { "creator_type": "author", "first_name": "Katerina", "last_name": "Lukavska", "name": null }, { "creator_type": "author", "first_name": "Percy", "last_name": "Mayta-Tristan", "name": null }, { "creator_type": "author", "first_name": "Dan J.", "last_name": "Miller", "name": null }, { "creator_type": "author", "first_name": "Olga", "last_name": "Orosova", "name": null }, { "creator_type": "author", "first_name": "Gabor", "last_name": "Orosz", "name": null }, { "creator_type": "author", "first_name": "Fernando P.", "last_name": "Ponce", "name": null }, { "creator_type": "author", "first_name": "Gonzalo R.", "last_name": "Quintana", "name": null }, { "creator_type": "author", "first_name": "Gabriel C.", "last_name": "Quintero Garzola", "name": null }, { "creator_type": "author", "first_name": "Jano", "last_name": "Ramos-Diaz", "name": null }, { "creator_type": "author", "first_name": "Kevin", "last_name": "Rigaud", "name": null }, { "creator_type": "author", "first_name": "Ann", "last_name": "Rousseau", "name": null }, { "creator_type": "author", "first_name": "Marco De", "last_name": "Tubino Scanavino", "name": null }, { "creator_type": "author", "first_name": "Marion K.", "last_name": "Schulmeyer", "name": null }, { "creator_type": "author", "first_name": "Pratap", "last_name": "Sharan", "name": null }, { "creator_type": "author", "first_name": "Mami", "last_name": "Shibata", "name": null }, { "creator_type": "author", "first_name": "Sheikh", "last_name": "Shoib", "name": null }, { "creator_type": "author", "first_name": "Vera", "last_name": "Sigre-Leiros", "name": null }, { "creator_type": "author", "first_name": "Luke", "last_name": "Sniewski", "name": null }, { "creator_type": "author", "first_name": "Ognen", "last_name": "Spasovski", "name": null }, { "creator_type": "author", "first_name": "Vesta", "last_name": "Steibliene", "name": null }, { "creator_type": "author", "first_name": "Dan J.", "last_name": "Stein", "name": null }, { "creator_type": "author", "first_name": "Berk C.", "last_name": "Unsal", "name": null }, { "creator_type": "author", "first_name": "Marie-Pier", "last_name": "Vaillancourt-Morel", "name": null }, { "creator_type": "author", "first_name": "Marie", "last_name": "Claire Van Hout", "name": null }, { "creator_type": "author", "first_name": "Beata", "last_name": "Bothe", "name": null } ], "identifiers": { "doi": { "normalized": "10.1177/10870547231215518" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "38180045" } }, "mesh": [ { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Attention Deficit Disorder with Hyperactivity", "descriptor_ui": "D001289", "major_topic": true }, { "descriptor": "Cross-Cultural Comparison", "descriptor_ui": "D003431", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Reproducibility of Results", "descriptor_ui": "D015203", "major_topic": false }, { "descriptor": "Self Report", "descriptor_ui": "D057566", "major_topic": false }, { "descriptor": "Surveys and Questionnaires", "descriptor_ui": "D011795", "major_topic": false } ], "publication": { "conference_name": null, "date": "2024 Jan 5", "date_precision": "day", "issue": "", "normalized_date": "2024-01-05", "pages": "10870547231215518", "proceedings_title": null, "publisher": "", "title": "Journal of attention disorders", "volume": "", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Cross-Cultural Adult ADHD Assessment in 42 Countries Using the Adult ADHD Self-Report Scale Screener.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Innate immunity plays an important role in host defense against microbial infections. It also participates in activation of acquired immunity through cytokine production and antigen presentation. Pattern recognition receptors such as Toll-like receptors and nucleotide oligomerization domain-like receptors sense invading pathogens and associated tissue injury, after which inflammatory mediators such as pro-inflammatory cytokines and nitric oxide are induced. Supersulfides are molecular species possessing catenated sulfur atoms such as persulfide and polysulfide moieties. They have recently been recognized as important regulators in cellular redox homeostasis by acting as potent antioxidants and nucleophiles. In addition, recent studies suggested that supersulfides are critically involved in the regulation of innate immune and inflammatory responses. In this review, we summarize current knowledge of the chemistry and biology of supersulfides, with particular attention to their roles in regulation of innate immune and inflammatory responses. Studies with animal models of infection and inflammation demonstrated the potent anti-inflammatory functions of supersulfides such as blocking pro-inflammatory signaling cascades, reducing oxidative stresses, and inhibiting replication of microbial pathogens including severe acute respiratory syndrome coronavirus 2. Precise understanding of how supersulfides regulate innate immune responses is the necessary requirement for developing supersulfide-based diagnostic as well as therapeutic strategies against inflammatory disorders.", "classifications": [ { "id": "JPMJCR2024", "label": "JPMJCR2024", "researcher": "Motohiro Nishida", "type": "grant" }, { "id": "Akaike", "label": "Group Akaike", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Group Nishida", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Hiroyasu", "last_name": "Tsutsuki", "name": null }, { "creator_type": "author", "first_name": "Tianli", "last_name": "Zhang", "name": null }, { "creator_type": "author", "first_name": "Takaaki", "last_name": "Akaike", "name": null }, { "creator_type": "author", "first_name": "Tomohiro", "last_name": "Sawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1093/intimm/dxad057" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "38180817" } }, "mesh": [ { "descriptor": "Adaptive Immunity", "descriptor_ui": "D056704", "major_topic": true }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cytokines", "descriptor_ui": "D016207", "major_topic": false }, { "descriptor": "Immunity, Innate", "descriptor_ui": "D007113", "major_topic": true }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Toll-Like Receptors", "descriptor_ui": "D051193", "major_topic": false } ], "publication": { "conference_name": null, "date": "2024 Jan 5", "date_precision": "day", "issue": "", "normalized_date": "2024-01-05", "pages": "dxad057", "proceedings_title": null, "publisher": "", "title": "International immunology", "volume": "", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Regulation of innate immune and inflammatory responses by supersulfides.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Supersulfides, which are defined as sulfur species with catenated sulfur atoms, are increasingly being investigated in biology. We recently identified pyridoxal phosphate (PLP)-dependent biosynthesis of cysteine persulfide (CysSSH) and related supersulfides by cysteinyl-tRNA synthetase (CARS). Here, we investigated the physiological role of CysSSH in budding yeast (Saccharomyces cerevisiae) by generating a PLP-binding site mutation K109A in CRS1 (the yeast ortholog of CARS), which decreased the synthesis of CysSSH and related supersulfides and also led to reduced chronological aging, effects that were associated with an increased endoplasmic reticulum stress response and impaired mitochondrial bioenergetics. Reduced chronological aging in the K109A mutant could be rescued by using exogenous supersulfide donors. Our findings indicate important roles for CARS in the production and metabolism of supersulfides-to mediate mitochondrial function and to regulate longevity.", "classifications": [ { "id": "JPMJCR2024", "label": "JPMJCR2024", "researcher": "Motohiro Nishida", "type": "grant" }, { "id": "Akaike", "label": "Group Akaike", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Group Nishida", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Akira", "last_name": "Nishimura", "name": null }, { "creator_type": "author", "first_name": "Sunghyeon", "last_name": "Yoon", "name": null }, { "creator_type": "author", "first_name": "Tetsuro", "last_name": "Matsunaga", "name": null }, { "creator_type": "author", "first_name": "Tomoaki", "last_name": "Ida", "name": null }, { "creator_type": "author", "first_name": "Minkyung", "last_name": "Jung", "name": null }, { "creator_type": "author", "first_name": "Seiryo", "last_name": "Ogata", "name": null }, { "creator_type": "author", "first_name": "Masanobu", "last_name": "Morita", "name": null }, { "creator_type": "author", "first_name": "Jun", "last_name": "Yoshitake", "name": null }, { "creator_type": "author", "first_name": "Yuka", "last_name": "Unno", "name": null }, { "creator_type": "author", "first_name": "Uladzimir", "last_name": "Barayeu", "name": null }, { "creator_type": "author", "first_name": "Tsuyoshi", "last_name": "Takata", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Takagi", "name": null }, { "creator_type": "author", "first_name": "Hozumi", "last_name": "Motohashi", "name": null }, { "creator_type": "author", "first_name": "Albert", "last_name": "van der Vliet", "name": null }, { "creator_type": "author", "first_name": "Takaaki", "last_name": "Akaike", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.redox.2023.103018" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "38199039" } }, "mesh": [ { "descriptor": "Longevity", "descriptor_ui": "D008136", "major_topic": true }, { "descriptor": "Mitochondria", "descriptor_ui": "D008928", "major_topic": false }, { "descriptor": "Saccharomyces cerevisiae", "descriptor_ui": "D012441", "major_topic": false }, { "descriptor": "Saccharomyces cerevisiae Proteins", "descriptor_ui": "D029701", "major_topic": true }, { "descriptor": "Sulfur", "descriptor_ui": "D013455", "major_topic": false } ], "publication": { "conference_name": null, "date": "2024 Jan 3", "date_precision": "day", "issue": "", "normalized_date": "2024-01-03", "pages": "103018", "proceedings_title": null, "publisher": "", "title": "Redox biology", "volume": "69", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Longevity control by supersulfide-mediated mitochondrial respiration and regulation of protein quality.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Seed germination of a parasitic plant Striga hermonthica is elicited by strigolactones which are exuded from roots of host plants. Here, we describe a high-throughput germination assay and a method for visualizing in vivo strigolactone receptor functions with a fluorogenic probe.", "classifications": [ { "id": "Tsuchiya", "label": "Group Tsuchiya", "parent": "Tsuchiya", "type": "group" }, { "id": "Tsuchiya", "label": "Team Tsuchiya", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Jia Xin", "last_name": "Yap", "name": null }, { "creator_type": "author", "first_name": "Yuichiro", "last_name": "Tsuchiya", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/978-1-0716-3965-8_5" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "38977567" } }, "mesh": [ { "descriptor": "Fluorescent Dyes", "descriptor_ui": "D005456", "major_topic": false }, { "descriptor": "Germination", "descriptor_ui": "D018525", "major_topic": true }, { "descriptor": "Lactones", "descriptor_ui": "D007783", "major_topic": true }, { "descriptor": "Molecular Probes", "descriptor_ui": "D015335", "major_topic": false }, { "descriptor": "Plant Roots", "descriptor_ui": "D018517", "major_topic": false }, { "descriptor": "Seeds", "descriptor_ui": "D012639", "major_topic": true }, { "descriptor": "Striga", "descriptor_ui": "D034362", "major_topic": true } ], "publication": { "conference_name": null, "date": "2024", "date_precision": "year", "issue": "", "normalized_date": "2024", "pages": "51-62", "proceedings_title": null, "publisher": "", "title": "Methods in molecular biology (Clifton, N.J.)", "volume": "2830", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Assessing Seed Germination Response of Parasitic Plant Striga hermonthica with Small-Molecule Probes.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Cell-cell interaction mediated by secreted and adhesive signaling molecules forms the basis of the coordinated cell movements (i.e., collective cell migration) observed in developing embryos, regenerating tissues, immune cells, and metastatic cancer. Decoding the underlying input/output rules at the single-cell level, however, remains a challenge due to the vast complexity in the extracellular environments that support such cellular behaviors. The amoebozoa Dictyostelium discoideum uses GPCR-mediated chemotaxis and cell-cell contact signals mediated by adhesion proteins with immunoglobulin-like folds to form a collectively migrating slug. Coordinated migration and repositioning of the cells in this relatively simple morphogenetic system are driven strictly by regulation of actin cytoskeleton by these signaling factors. Its unique position in the eukaryotic tree of life outside metazoa points to basic logics of tissue self-organization that are common across taxa. Here, we describe a method to reconstitute intercellular contact signals and the resulting cell polarization using purified adhesion proteins. In addition, a protocol using a microfluidic chamber is laid out where one can study how the cell-cell contact signal and chemoattractant signals, when simultaneously presented, are interpreted. Quantitative image analysis for obtaining cell morphology features is also provided. A similar approach should be applicable to study other collectively migrating cells.", "classifications": [ { "id": "JPMJCR1923", "label": "JPMJCR1923", "researcher": "Satoshi Sawai", "type": "grant" }, { "id": "Sawai", "label": "Group Sawai", "parent": "Sawai", "type": "group" }, { "id": "Sawai", "label": "Team Sawai", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Taihei", "last_name": "Fujimori", "name": null }, { "creator_type": "author", "first_name": "Hidenori", "last_name": "Hashimura", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Sawai", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/978-1-0716-4023-4_3" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "39147967" } }, "mesh": [ { "descriptor": "Cell Adhesion", "descriptor_ui": "D002448", "major_topic": false }, { "descriptor": "Cell Communication", "descriptor_ui": "D002450", "major_topic": true }, { "descriptor": "Cell Movement", "descriptor_ui": "D002465", "major_topic": true }, { "descriptor": "Cell Polarity", "descriptor_ui": "D016764", "major_topic": false }, { "descriptor": "Chemotaxis", "descriptor_ui": "D002633", "major_topic": true }, { "descriptor": "Dictyostelium", "descriptor_ui": "D004023", "major_topic": true }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false } ], "publication": { "conference_name": null, "date": "2024", "date_precision": "year", "issue": "", "normalized_date": "2024", "pages": "23-36", "proceedings_title": null, "publisher": "", "title": "Methods in molecular biology (Clifton, N.J.)", "volume": "2828", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Imaging-Based Analysis of Cell-Cell Contact-Dependent Migration in Dictyostelium.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The measurement of cellular forces, which reflect crucial biological attributes, has the potential to replace conventional cell assessment methods, such as morphology, proliferation, and molecular expression analysis, in medical cell diagnosis and cell culture studies. In medical cell evaluations, force inference techniques have gained prominence due to their non-invasiveness and lack of requirement for specialized equipment. Among those techniques, the method proposed by Ishihara et al., which estimates forces in densely packed cells based only on cell geometry, is a promising method. However, its applicability range of this method has not been fully established. In this study, we employed a two-dimensional vertex model to numerically assess the applicability of this method on homogeneous and heterogeneous cells. Our comparisons between the true values from numerical simulations and the estimated values from the inference method revealed a significant correlation between estimation accuracy and cell roundness in systems of homogeneous cell. Moreover, the method demonstrated efficient force estimations in heterogeneous-cell systems. These findings may be useful when the force inference method is employed to evaluate medical cells.", "classifications": [ { "id": "Okuda", "label": "Group Okuda", "parent": "Imayoshi", "type": "group" }, { "id": "Imayoshi", "label": "Team Imayoshi", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Shou", "last_name": "Miyasaka", "name": null }, { "creator_type": "author", "first_name": "Keita", "last_name": "Izumi", "name": null }, { "creator_type": "author", "first_name": "Satoru", "last_name": "Okuda", "name": null }, { "creator_type": "author", "first_name": "Yuichiro", "last_name": "Miki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1371/journal.pone.0299016" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "38625886" } }, "mesh": [ { "descriptor": "Biomechanical Phenomena", "descriptor_ui": "D001696", "major_topic": false }, { "descriptor": "Mechanical Phenomena", "descriptor_ui": "D055595", "major_topic": true } ], "publication": { "conference_name": null, "date": "2024", "date_precision": "year", "issue": "4", "normalized_date": "2024", "pages": "e0299016", "proceedings_title": null, "publisher": "", "title": "PloS one", "volume": "19", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Numerical assessment of the applicability of geometry-based force inference on homogeneous and heterogeneous cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Aim: Composite population of myofibroblasts (MFs) within myocardial tissue is known to alter impulse propagation, leading to arrhythmias. However, it remains unclear whether and how MFs alter their propagation patterns when contacting cardiomyocytes (CMs) without complex structural insertions in the myocardium. We attempted to unveil the effects of the one-sided, heterocellular CM-MF connection on the impulse propagation of CM monolayers without the spatial insertion of MFs as an electrical or mechanical obstacle. Methods and results: We evaluated fluo8-based spatiotemporal patterns in impulse propagation of neonatal rat CM monolayers cultured on the microporous membrane having 8-mum diameter pores with co-culture of MFs or CMs on the reverse membrane side (CM-MF model or CM-CM model, respectively). During consecutive pacing at 1 or 2 Hz, the CM monolayers exhibited forward impulse propagation from the pacing site with a slower conduction velocity (theta) and a larger coefficient of directional theta variation in the CM-MF model than that in the CM-CM model in a frequency-dependent manner (2 Hz >1 Hz). The localized placement of an MF cluster on the reverse side resulted in an abrupt segmental depression of the impulse propagation of the upper CM layer, causing a spatiotemporally non-uniform pattern. Dye transfer of the calcein loaded in the upper CM layer to the lower MF layer was attenuated by the gap-junction inhibitor heptanol. Immunocytochemistry identified definitive connexin 43 (Cx43) between the CMs and MFs in the membrane pores. MF-selective Cx43 knockdown in the MF layer improved both the velocity and uniformity of propagation in the CM monolayer. Conclusion: Heterocellular Cx43 gap junction coupling of CMs with MFs alters the spatiotemporal patterns of myocardial impulse propagation, even in the absence of spatially interjacent and mechanosensitive modulations by MFs. Moreover, MFs can promote pro-arrhythmogenic impulse propagation when in face-to-face contact with the myocardium that arises in the healing infarct border zone.", "classifications": [ { "id": "JPMJCR1925", "label": "JPMJCR1925", "researcher": "Katsumasa Fujita", "type": "grant" }, { "id": "Fujita", "label": "Group Fujita", "parent": "Fujita", "type": "group" }, { "id": "Tanaka", "label": "Group Tanaka", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yumika", "last_name": "Tsuji", "name": null }, { "creator_type": "author", "first_name": "Takehiro", "last_name": "Ogata", "name": null }, { "creator_type": "author", "first_name": "Kentaro", "last_name": "Mochizuki", "name": null }, { "creator_type": "author", "first_name": "Shoko", "last_name": "Tamura", "name": null }, { "creator_type": "author", "first_name": "Yuma", "last_name": "Morishita", "name": null }, { "creator_type": "author", "first_name": "Tetsuro", "last_name": "Takamatsu", "name": null }, { "creator_type": "author", "first_name": "Satoaki", "last_name": "Matoba", "name": null }, { "creator_type": "author", "first_name": "Hideo", "last_name": "Tanaka", "name": null } ], "identifiers": { "doi": { "normalized": "10.3389/fphys.2024.1352911" }, "pmcid": { "normalized": "PMC10920281" }, "pmid": { "normalized": "38465264" } }, "mesh": [], "publication": { "conference_name": null, "date": "2024", "date_precision": "year", "issue": "", "normalized_date": "2024", "pages": "1352911", "proceedings_title": null, "publisher": "", "title": "Frontiers in physiology", "volume": "15", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Myofibroblasts impair myocardial impulse propagation by heterocellular connexin43 gap-junctional coupling through micropores.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Human induced pluripotent stem cells (hiPSCs) are an attractive cell source for regenerative medicine. For its widespread use as a starting material, a robust storage and distribution system in the frozen state is necessary. For this system, managing transient warming during storage and transport is essential, but how transient warming affects cells and the mechanisms involved are not yet fully understood. This study examined the influence of temperature cyclings (from −80°C to −150°C) on cryopreserved hiPSCs using a custom-made cryo Raman microscope, flow cytometry, and performance indices to assess viability. Raman spectroscopy indicated the disappearance of mitochondrial cytochrome signals after thawing. A reduction in the mitochondrial membrane potential was detected using flow cytometry. The performance indices indicated a decrease in attachment efficiency with an increase in the number of temperature cycles. This decrease was observed in the temperature cycle range above the glass transition temperature of the cryoprotectant. Raman observations captured an increase in the signal intensity of intracellular dimethyl sulfoxide (DMSO) during temperature cycles. Based on these results, we proposed a schematic illustration for cellular responses to temperature fluctuations, suggesting that temperature fluctuations above the glass-transition temperature trigger the movement of DMSO, leading to cytochrome c oxidation, mitochondrial damage, and caspase-mediated cell death. This enhances our understanding of the key events during cryopreservation and informs the development of quality control strategies for hiPSC storage and transport.", "classifications": [ { "id": "JPMJCR1925", "label": "JPMJCR1925", "researcher": "Katsumasa Fujita", "type": "grant" }, { "id": "Fujita", "label": "Group Fujita", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Jun", "last_name": "Okuda", "name": null }, { "creator_type": "author", "first_name": "Namiko", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Tetsuji", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Kenta", "last_name": "Mizushima", "name": null }, { "creator_type": "author", "first_name": "Heqi", "last_name": "Xi", "name": null }, { "creator_type": "author", "first_name": "Yasuaki", "last_name": "Kumamoto", "name": null }, { "creator_type": "author", "first_name": "Katsumasa", "last_name": "Fujita", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Kino-Oka", "name": null } ], "identifiers": { "doi": { "normalized": "10.3389/fbioe.2024.1443795" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "39139293" } }, "mesh": [], "publication": { "conference_name": null, "date": "2024", "date_precision": "year", "issue": "", "normalized_date": "2024", "pages": "", "proceedings_title": null, "publisher": "", "title": "Frontiers in Bioengineering and Biotechnology", "volume": "12", "year": 2024 }, "ssbd": { "database": [], "repository": [ "ssbd-repos-000472" ] }, "title": "The impact of repeated temperature cycling on cryopreserved human iPSC viability stems from cytochrome redox state changes.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Motivation: Visualization and analysis of biological networks play crucial roles in understanding living systems. Biological networks include diverse types, from gene regulatory networks and protein–protein interactions to metabolic networks. Metabolic networks include substrates, products, and enzymes, which are regulated by allosteric mechanisms and gene expression. However, the analysis of these diverse omics types is challenging due to the diversity of databases and the complexity of network analysis. Results: We developed iTraNet, a web application that visualizes and analyses trans-omics networks involving four types of networks: gene regulatory networks, protein–protein interactions, metabolic networks, and metabolite exchange networks. Using iTraNet, we found that in wild-type mice, hub molecules within the network tended to respond to glucose administration, whereas in ob/ob mice, this tendency disappeared. With its ability to facilitate network analysis, we anticipate that iTraNet will help researchers gain insights into living systems. Availability and implementation: iTraNet is available at https://itranet.streamlit.app/.", "classifications": [ { "id": "JPMJCR2123", "label": "JPMJCR2123", "researcher": "Shinya Kuroda", "type": "grant" }, { "id": "Kuroda", "label": "Group Kuroda", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Hikaru", "last_name": "Sugimoto", "name": null }, { "creator_type": "author", "first_name": "Keigo", "last_name": "Morita", "name": null }, { "creator_type": "author", "first_name": "Dongzi", "last_name": "Li", "name": null }, { "creator_type": "author", "first_name": "Yunfan", "last_name": "Bai", "name": null }, { "creator_type": "author", "first_name": "Matthias", "last_name": "Mattanovich", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Kuroda", "name": null } ], "identifiers": { "doi": { "normalized": "10.1093/bioadv/vbae141" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "39440006" } }, "mesh": [], "publication": { "conference_name": null, "date": "2024", "date_precision": "year", "issue": "1", "normalized_date": "2024", "pages": "", "proceedings_title": null, "publisher": "", "title": "Bioinformatics Advances", "volume": "4", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "iTraNet: a web-based platform for integrated trans-omics network visualization and analysis.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "A 64-year-old woman presented with fine motor impairment in both hands. MRI revealed a contrast-enhanced lesion in the medulla oblongata. Lymphoid cells with abnormal blebs were observed and a CD4(+)/CD8(+) double positive (DP) T cell population was detected by flow cytometry (FCM) in the bone marrow (BM) and the peripheral blood (PB). CLEC16A::IL2 fusion gene was identified by whole exome sequencing with DNA prepared from DP T cells. Clonal rearrangement of the T-cell receptor gene and expression of TCL1A protein were detected. This led to a diagnosis of T-cell prolymphocytic leukemia (T-PLL) with central nervous system (CNS) infiltration. Abnormal cells in BM and PB became undetectable on microscopy and FCM, and the CNS lesion disappeared on MRI after second-line therapy with alemtuzumab. Meanwhile, the CLEC16A::IL2 fusion mRNA remained detectable in PB. Allogeneic hematopoietic stem-cell transplantation was performed, and the fusion mRNA has now been undetectable for more than 5 years since transplantation. This is the first report of a T-PLL case with a CLEC16A::IL2 fusion gene.", "classifications": [ { "id": "Nishikii", "label": "Group Nishikii", "parent": "Shintaku", "type": "group" }, { "id": "Shintaku", "label": "Team Shintaku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Haruka", "last_name": "Momose", "name": null }, { "creator_type": "author", "first_name": "Naoki", "last_name": "Kurita", "name": null }, { "creator_type": "author", "first_name": "Hidekazu", "last_name": "Nishikii", "name": null }, { "creator_type": "author", "first_name": "Nozomi", "last_name": "Yusa", "name": null }, { "creator_type": "author", "first_name": "Kazuaki", "last_name": "Yokoyama", "name": null }, { "creator_type": "author", "first_name": "Eigo", "last_name": "Shimizu", "name": null }, { "creator_type": "author", "first_name": "Seiya", "last_name": "Imoto", "name": null }, { "creator_type": "author", "first_name": "Toru", "last_name": "Nanmoku", "name": null }, { "creator_type": "author", "first_name": "Yumiko", "last_name": "Maruyama", "name": null }, { "creator_type": "author", "first_name": "Tatsuhiro", "last_name": "Sakamoto", "name": null }, { "creator_type": "author", "first_name": "Yasuhisa", "last_name": "Yokoyama", "name": null }, { "creator_type": "author", "first_name": "Takayasu", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Ryota", "last_name": "Matsuoka", "name": null }, { "creator_type": "author", "first_name": "Naoshi", "last_name": "Obara", "name": null }, { "creator_type": "author", "first_name": "Mamiko", "last_name": "Sakata-Yanagimoto", "name": null }, { "creator_type": "author", "first_name": "Shigeru", "last_name": "Chiba", "name": null } ], "identifiers": { "doi": { "normalized": "10.11406/rinketsu.65.35" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "38311387" } }, "mesh": [ { "descriptor": "Alemtuzumab", "descriptor_ui": "D000074323", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Hematopoietic Stem Cell Transplantation", "descriptor_ui": "D018380", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Interleukin-2", "descriptor_ui": "D007376", "major_topic": false }, { "descriptor": "Lectins, C-Type", "descriptor_ui": "D037181", "major_topic": false }, { "descriptor": "Leukemia, Prolymphocytic, T-Cell", "descriptor_ui": "D015461", "major_topic": true }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Monosaccharide Transport Proteins", "descriptor_ui": "D009004", "major_topic": false }, { "descriptor": "RNA, Messenger", "descriptor_ui": "D012333", "major_topic": false } ], "publication": { "conference_name": null, "date": "2024", "date_precision": "year", "issue": "1", "normalized_date": "2024", "pages": "35-40", "proceedings_title": null, "publisher": "", "title": "[Rinsho ketsueki] The Japanese journal of clinical hematology", "volume": "65", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "[Durable remission of T-cell prolymphocytic leukemia with CLEC16A::IL2 after allogeneic hematopoietic stem cell transplantation].", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Primordial follicle activation (PFA) is a pivotal event in female reproductive biology, coordinating the transition from quiescent to growing follicles. This study employed comprehensive single-cell RNA sequencing to gain insights into the detailed regulatory mechanisms governing the synchronized dormancy and activation between granulosa cells (GCs) and oocytes with the progression of the PFA process. Wntless (Wls) conditional knockout (cKO) mice served as a unique model, suppressing the transition from pre-GCs to GCs, and disrupting somatic cell-derived WNT signaling in the ovary. Our data revealed immediate transcriptomic changes in GCs post-PFA in Wls cKO mice, leading to a divergent trajectory, while oocytes exhibited modest transcriptomic alterations. Subpopulation analysis identified the molecular pathways affected by WNT signaling on GC maturation, along with specific gene signatures linked to dormant and activated oocytes. Despite minimal evidence of continuous up-regulation of dormancy-related genes in oocytes, the loss of WNT signaling in (pre-)GCs impacted gene expression in oocytes even before PFA, subsequently influencing them globally. The infertility observed in Wls cKO mice was attributed to compromised GC-oocyte molecular crosstalk and the microenvironment for oocytes. Our study highlights the pivotal role of the WNT-signaling pathway and its molecular signature, emphasizing the importance of intercellular crosstalk between (pre-)GCs and oocytes in orchestrating folliculogenesis.", "classifications": [ { "id": "Nikaido", "label": "Group Nikaido", "parent": "Fujiwara", "type": "group" }, { "id": "Fujiwara", "label": "Team Fujiwara", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Hinako M.", "last_name": "Takase", "name": null }, { "creator_type": "author", "first_name": "Tappei", "last_name": "Mishina", "name": null }, { "creator_type": "author", "first_name": "Tetsutaro", "last_name": "Hayashi", "name": null }, { "creator_type": "author", "first_name": "Mika", "last_name": "Yoshimura", "name": null }, { "creator_type": "author", "first_name": "Mariko", "last_name": "Kuse", "name": null }, { "creator_type": "author", "first_name": "Itoshi", "last_name": "Nikaido", "name": null }, { "creator_type": "author", "first_name": "Tomoya S.", "last_name": "Kitajima", "name": null } ], "identifiers": { "doi": { "normalized": "10.1371/journal.pone.0311978" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "39441825" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Communication", "descriptor_ui": "D002450", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Granulosa Cells", "descriptor_ui": "D006107", "major_topic": true }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Oocytes", "descriptor_ui": "D009865", "major_topic": true }, { "descriptor": "Ovarian Follicle", "descriptor_ui": "D006080", "major_topic": true }, { "descriptor": "Single-Cell Analysis", "descriptor_ui": "D059010", "major_topic": false }, { "descriptor": "Transcriptome", "descriptor_ui": "D059467", "major_topic": true }, { "descriptor": "Wnt Signaling Pathway", "descriptor_ui": "D060449", "major_topic": true } ], "publication": { "conference_name": null, "date": "2024", "date_precision": "year", "issue": "10", "normalized_date": "2024", "pages": "e0311978", "proceedings_title": null, "publisher": "", "title": "PloS one", "volume": "19", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Transcriptomic signatures of WNT-driven pathways and granulosa cell-oocyte interactions during primordial follicle activation.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "During leaf development, the timing of transition from cell proliferation to expansion is an important factor in determining the final organ size. However, the regulatory system involved in this transition remains less understood. To get an insight into this system, we investigated the compensation phenomenon, in which the cell number decreases while the cell size increases in organs with determinate growth. Compensation is observed in several plant species suggesting coordination between cell proliferation and expansion. In this study, we examined an Arabidopsis mutant of ANGUSTIFOLIA 3 (AN3)/GRF-INTERACTING FACTOR 1, a positive regulator of cell proliferation, which exhibits the compensation. Though the AN3 role has been extensively investigated, the mechanism underlying excess cell expansion in the an3 mutant remains unknown. Focusing on the early stage of leaf development, we performed kinematic, cytological, biochemical, and transcriptome analyses, and found that the cell size had already increased during the proliferation phase, with active cell proliferation in the an3 mutant. Moreover, at this stage, chloroplasts, vacuoles, and xylem cells developed earlier than in the wild-type cells. Transcriptome data showed that photosynthetic activity and secondary cell wall biosynthesis were activated in an3 proliferating cells. These results indicated that precocious cell differentiation occurs in an3 cells. Therefore, we suggest a novel AN3 role in the suppression of cell expansion/differentiation during the cell proliferation phase.", "classifications": [ { "id": "Higaki", "label": "Group Higaki", "parent": "Ueda", "type": "group" }, { "id": "Ueda", "label": "Team Ueda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Kazune", "last_name": "Ezaki", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Koga", "name": null }, { "creator_type": "author", "first_name": "Noriko", "last_name": "Takeda-Kamiya", "name": null }, { "creator_type": "author", "first_name": "Kiminori", "last_name": "Toyooka", "name": null }, { "creator_type": "author", "first_name": "Takumi", "last_name": "Higaki", "name": null }, { "creator_type": "author", "first_name": "Shingo", "last_name": "Sakamoto", "name": null }, { "creator_type": "author", "first_name": "Hirokazu", "last_name": "Tsukaya", "name": null } ], "identifiers": { "doi": { "normalized": "10.3389/fpls.2024.1322223" }, "pmcid": { "normalized": "PMC11058843" }, "pmid": { "normalized": "38689848" } }, "mesh": [], "publication": { "conference_name": null, "date": "2024", "date_precision": "year", "issue": "", "normalized_date": "2024", "pages": "1322223", "proceedings_title": null, "publisher": "", "title": "Frontiers in plant science", "volume": "15", "year": 2024 }, "ssbd": { "database": [ "ssbd-database-000456" ], "repository": [ "ssbd-repos-000456" ] }, "title": "Precocious cell differentiation occurs in proliferating cells in leaf primordia in Arabidopsis angustifolia3 mutant.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Glucose metabolism is a key factor characterizing the cellular state during multicellular development. In metazoans, the metabolic state of undifferentiated cells correlates with growth/differentiation transition and cell fate determination. Notably, the cell fate of the Amoebozoa species Dictyostelium discoideum is biased by the presence of glucose and is also correlated with early differences in intracellular ATP. However, the relationship between early cell–cell heterogeneity, cell differentiation, and the metabolic state is unclear. To address the link between glucose metabolism and cell differentiation in D. discoideum, we studied the role of phosphoenolpyruvate carboxylase (PEPC), a key enzyme in the PEP-oxaloacetate-pyruvate node, a core junction that dictates the metabolic flux of glycolysis, the TCA cycle, and gluconeogenesis. We demonstrate that there is cell–cell heterogeneity in PEPC promoter activity in vegetative cells, which depends on nutrient conditions, and that cells with high PEPC promoter activity differentiate into spores. The PEPC null mutant exhibited an aberrantly high prestalk/prespore ratio, and the spore mass of the fruiting body was glassy and consisted of immature spores. Furthermore, the PEPC null mutant had high ATP levels and low mitochondrial membrane potential. Our results suggest the importance of cell–cell heterogeneity in the levels of metabolic enzymes during early cell fate priming.", "classifications": [ { "id": "JPMJCR1923", "label": "JPMJCR1923", "researcher": "Satoshi Sawai", "type": "grant" }, { "id": "Sawai", "label": "Group Sawai", "parent": "Sawai", "type": "group" }, { "id": "Sawai", "label": "Team Sawai", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Kenichi", "last_name": "Abe", "name": null }, { "creator_type": "author", "first_name": "Hidenori", "last_name": "Hashimura", "name": null }, { "creator_type": "author", "first_name": "Haruka", "last_name": "Hiraoka", "name": null }, { "creator_type": "author", "first_name": "Shoko", "last_name": "Fujishiro", "name": null }, { "creator_type": "author", "first_name": "Narufumi", "last_name": "Kameya", "name": null }, { "creator_type": "author", "first_name": "Kazuteru", "last_name": "Taoka", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Kuwana", "name": null }, { "creator_type": "author", "first_name": "Masashi", "last_name": "Fukuzawa", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Sawai", "name": null } ], "identifiers": { "doi": { "normalized": "10.3389/fcell.2024.1526795" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "39968235" } }, "mesh": [], "publication": { "conference_name": null, "date": "2024", "date_precision": "year", "issue": "", "normalized_date": "2024", "pages": "", "proceedings_title": null, "publisher": "", "title": "Frontiers in Cell and Developmental Biology", "volume": "12", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Cell–cell heterogeneity in phosphoenolpyruvate carboxylase biases early cell fate priming in Dictyostelium discoideum.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Over the last decade, the use of microfabricated substrates has proven pivotal for studying the effect of substrate topography on cell deformation and migration. Microfabrication techniques allow one to construct a transparent substrate with topographic features with high designability and reproducibility and thus well suited to experiments that microscopically address how spatial and directional bias are brought about in the cytoskeletal machineries and hence cell motility. While much of the progress in this avenue of study has so far been made in adhesive cells of epithelial and mesenchymal nature, whether related phenomena exist in less adhesive fast migrating cells is relatively unknown. In this chapter, we describe a method that makes use of micrometer-scale ridges to study fast-migrating Dictyostelium cells where it was recently shown that membrane evagination associated with macropinocytic cup formation plays a pivotal role in the topography sensing. The method requires only basic photolithography, and thus the step-by-step protocol should be a good entry point for cell biologists looking to incorporate similar microfabrication approaches.", "classifications": [ { "id": "JPMJCR1923", "label": "JPMJCR1923", "researcher": "Satoshi Sawai", "type": "grant" }, { "id": "Sawai", "label": "Group Sawai", "parent": "Sawai", "type": "group" }, { "id": "Sawai", "label": "Team Sawai", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Gen", "last_name": "Honda", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Sawai", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/978-1-0716-3894-1_11" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "38954204" } }, "mesh": [ { "descriptor": "Cell Adhesion", "descriptor_ui": "D002448", "major_topic": false }, { "descriptor": "Cell Movement", "descriptor_ui": "D002465", "major_topic": true }, { "descriptor": "Dictyostelium", "descriptor_ui": "D004023", "major_topic": true }, { "descriptor": "Microtechnology", "descriptor_ui": "D055616", "major_topic": true } ], "publication": { "conference_name": null, "date": "2024", "date_precision": "year", "issue": "", "normalized_date": "2024", "pages": "149-161", "proceedings_title": null, "publisher": "", "title": "Methods in molecular biology (Clifton, N.J.)", "volume": "2814", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Analyzing the Micro-topography Guidance of Dictyostelium Cells Using Microfabricated Structures.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The functional significance of the morphological and genetic changes that occurred in the brain during evolution is not fully understood. Here we show the relationships between evolutionary changes of the brain and glymphatic circulation. We establish a mathematical model to simulate glymphatic circulation in the cerebral hemispheres, and our results show that cortical neurons accumulate in areas of the cerebral hemispheres where glymphatic circulation is highly efficient. We also find that cortical folds markedly enhance the efficiency of glymphatic circulation in the cerebral hemispheres. Furthermore, our in vivo study using ferrets reveals sulcus-dominant cerebrospinal fluid (CSF) influx, which enhances the efficiency of glymphatic circulation in the enlarged cerebral hemispheres of gyrencephalic brains. Sulcus-dominant CSF influx is mediated by preferential expression of aquaporin-4 in sulcal regions, and similar expression patterns of aquaporin-4 are also found in human cerebral hemispheres. These results indicate that evolutionary changes in the cerebral hemispheres are related to improved efficiency of glymphatic circulation. It seems plausible that the efficiency of glymphatic circulation is an important factor determining the evolutionary trajectory of the cerebral hemispheres.", "classifications": [ { "id": "JPMJCR1921", "label": "JPMJCR1921", "researcher": "Itaru Imayoshi", "type": "grant" }, { "id": "Imayoshi", "label": "Group Imayoshi", "parent": "Imayoshi", "type": "group" }, { "id": "Okuda", "label": "Group Okuda", "parent": "Imayoshi", "type": "group" }, { "id": "Imayoshi", "label": "Team Imayoshi", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Narufumi", "last_name": "Kameya", "name": null }, { "creator_type": "author", "first_name": "Itsuki", "last_name": "Sakai", "name": null }, { "creator_type": "author", "first_name": "Kengo", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Toshihide", "last_name": "Hamabe-Horiike", "name": null }, { "creator_type": "author", "first_name": "Yohei", "last_name": "Shinmyo", "name": null }, { "creator_type": "author", "first_name": "Mitsutoshi", "last_name": "Nakada", "name": null }, { "creator_type": "author", "first_name": "Satoru", "last_name": "Okuda", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Kawasaki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41467-024-54372-1" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "39632840" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Aquaporin 4", "descriptor_ui": "D051401", "major_topic": true }, { "descriptor": "Biological Evolution", "descriptor_ui": "D005075", "major_topic": true }, { "descriptor": "Brain", "descriptor_ui": "D001921", "major_topic": false }, { "descriptor": "Cerebrospinal Fluid", "descriptor_ui": "D002555", "major_topic": false }, { "descriptor": "Cerebrum", "descriptor_ui": "D054022", "major_topic": false }, { "descriptor": "Ferrets", "descriptor_ui": "D005289", "major_topic": true }, { "descriptor": "Glymphatic System", "descriptor_ui": "D000077502", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false } ], "publication": { "conference_name": null, "date": "2024", "date_precision": "year", "issue": "", "normalized_date": "2024", "pages": "", "proceedings_title": null, "publisher": "", "title": "Nature Communications", "volume": "15", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Evolutionary changes leading to efficient glymphatic circulation in the mammalian brain.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "A 64-year-old man was diagnosed with diffuse large B-cell lymphoma (DLBCL). He achieved complete remission after R-CHOP therapy, but experienced relapse as lymphoplasmacytic lymphoma (LPL) 4 years after initial treatment. He was retreated with R-bendamustine therapy, resulting in a second remission. However, he once again experienced relapse as DLBCL 2 years later. Although lymph node lesions disappeared after salvage chemotherapy, facial and hypoglossal nerve paresis due to tumor infiltration appeared. His symptoms were attributed to cranial nerve invasion of transformed LPL, and treatment with tirabrutinib was started. Neurological symptoms markedly improved and high-dose chemotherapy followed by autologous stem cell transplantation was performed, resulting in long-term remission. Mutational analyses suggested that a B cell clone with MYD88 mutation caused the entire course of the disease, and our experience with this case indicates that Bruton's tyrosine kinase (BTK) inhibitor therapy might be effective for such cases.", "classifications": [ { "id": "Nishikii", "label": "Group Nishikii", "parent": "Shintaku", "type": "group" }, { "id": "Shintaku", "label": "Team Shintaku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Atsushi", "last_name": "Uehara", "name": null }, { "creator_type": "author", "first_name": "Hidekazu", "last_name": "Nishikii", "name": null }, { "creator_type": "author", "first_name": "Yasuhito", "last_name": "Suehara", "name": null }, { "creator_type": "author", "first_name": "Ryota", "last_name": "Matsuoka", "name": null }, { "creator_type": "author", "first_name": "Toru", "last_name": "Nanmoku", "name": null }, { "creator_type": "author", "first_name": "Kenichi", "last_name": "Makishima", "name": null }, { "creator_type": "author", "first_name": "Keiichiro", "last_name": "Hattori", "name": null }, { "creator_type": "author", "first_name": "Yuya", "last_name": "Sasaki", "name": null }, { "creator_type": "author", "first_name": "Yumiko", "last_name": "Maruyama", "name": null }, { "creator_type": "author", "first_name": "Tatsuhiro", "last_name": "Sakamoto", "name": null }, { "creator_type": "author", "first_name": "Takayasu", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Naoki", "last_name": "Kurita", "name": null }, { "creator_type": "author", "first_name": "Yasuhisa", "last_name": "Yokoyama", "name": null }, { "creator_type": "author", "first_name": "Naoshi", "last_name": "Obara", "name": null }, { "creator_type": "author", "first_name": "Mamiko", "last_name": "Sakata-Yanagimoto", "name": null }, { "creator_type": "author", "first_name": "Shigeru", "last_name": "Chiba", "name": null } ], "identifiers": { "doi": { "normalized": "10.11406/rinketsu.65.1368" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "39935223" } }, "mesh": [ { "descriptor": "Agammaglobulinaemia Tyrosine Kinase", "descriptor_ui": "D000077329", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Lymphoma, B-Cell", "descriptor_ui": "D016393", "major_topic": false }, { "descriptor": "Lymphoma, Large B-Cell, Diffuse", "descriptor_ui": "D016403", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": true }, { "descriptor": "Myeloid Differentiation Factor 88", "descriptor_ui": "D053594", "major_topic": true }, { "descriptor": "Protein Kinase Inhibitors", "descriptor_ui": "D047428", "major_topic": true }, { "descriptor": "Protein-Tyrosine Kinases", "descriptor_ui": "D011505", "major_topic": false }, { "descriptor": "Treatment Outcome", "descriptor_ui": "D016896", "major_topic": false }, { "descriptor": "Waldenstrom Macroglobulinemia", "descriptor_ui": "D008258", "major_topic": false } ], "publication": { "conference_name": null, "date": "2024", "date_precision": "year", "issue": "11", "normalized_date": "2024", "pages": "1368-1374", "proceedings_title": null, "publisher": "", "title": "[Rinsho ketsueki] The Japanese journal of clinical hematology", "volume": "65", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "[Successful BTK inhibitor therapy for refractory transformed B-cell lymphoma originating from an MYD88 mutant clone].", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: Biomarkers to predict the recurrence risk are required to optimize perioperative treatment. Adjuvant chemotherapy for patients with human epidermal growth factor 2-positive (HER2-positive) early breast cancer is decided by pathological responses of neoadjuvant chemotherapy (NAC). However, whether pathological responses are appropriate biomarkers is unclear. Currently, there are several studies using minimal residual disease (MRD) as a predictor of prognosis in solid tumors. However, there is no standard method for detecting MRD. OBJECTIVES: This study aimed at prospectively evaluating the relationship between MRD detection and recurrence in Asian patients with HER2-positive early breast cancer. DESIGN: Prospective, observational, single-group, and exploratory. This study will include 60 patients from 2 institutions in Japan and the Philippines. The invasive disease-free survival (IDFS) rates of the MRD-positive and MRD-negative groups are compared in patients with HER2-positive early breast cancer who undergo surgery after receiving NAC. METHODS AND ANALYSIS: Circulating tumor DNA (ctDNA) levels of patients will be evaluated 6 times: before NAC, after NAC, after surgery, and annually after surgery for 3 years. We will analyze the genetic profile of blood and tissue samples using the Todai OncoPanel (TOP) and the methylation level of DNA. The primary endpoint is IDFS. Secondary endpoints include overall survival (OS) and disease-free survival (DFS). Patient enrollment began in June 2022, and new participants are still being recruited. ETHICS: This study has been approved by the National Cancer Center Hospital Certified Review Board in March 2022 and has been approved by the Research Ethics Board of the participating center. DISCUSSION: Our findings will contribute to determining whether MRD detection using TOP is useful for predicting the recurrence of HER2-positive early breast cancer. If this is proven, MRD detected by TOP could be used in the future as a biomarker to assist in the de-/escalation of treatment strategies in the next interventional trial, thereby avoiding overtreatment in patients at low risk, and in the addition of intensive treatment modalities for those in patients at high risk.", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Momoko", "last_name": "Tokura", "name": null }, { "creator_type": "author", "first_name": "Mark Malalay", "last_name": "Ando", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Kojima", "name": null }, { "creator_type": "author", "first_name": "Rui", "last_name": "Kitadai", "name": null }, { "creator_type": "author", "first_name": "Shu", "last_name": "Yazaki", "name": null }, { "creator_type": "author", "first_name": "Cyrielle Marie N.", "last_name": "Atutubo", "name": null }, { "creator_type": "author", "first_name": "Rubi K.", "last_name": "Li", "name": null }, { "creator_type": "author", "first_name": "Minda Z.", "last_name": "Perez", "name": null }, { "creator_type": "author", "first_name": "Agnes E.", "last_name": "Gorospe", "name": null }, { "creator_type": "author", "first_name": "Manuelito A.", "last_name": "Madrid", "name": null }, { "creator_type": "author", "first_name": "Mel Valerie C.", "last_name": "Ordinario", "name": null }, { "creator_type": "author", "first_name": "Marcelo Severino B.", "last_name": "Imasa", "name": null }, { "creator_type": "author", "first_name": "Kazuki", "last_name": "Sudo", "name": null }, { "creator_type": "author", "first_name": "Tatsunori", "last_name": "Shimoi", "name": null }, { "creator_type": "author", "first_name": "Akihiko", "last_name": "Suto", "name": null }, { "creator_type": "author", "first_name": "Shinji", "last_name": "Kohsaka", "name": null }, { "creator_type": "author", "first_name": "Ryunosuke", "last_name": "Machida", "name": null }, { "creator_type": "author", "first_name": "Ryo", "last_name": "Sadachi", "name": null }, { "creator_type": "author", "first_name": "Masayuki", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null }, { "creator_type": "author", "first_name": "Tomomi", "last_name": "Hata", "name": null }, { "creator_type": "author", "first_name": "Kenichi", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Kan", "last_name": "Yonemori", "name": null }, { "creator_type": "author", "first_name": "Sho", "last_name": "Shiino", "name": null } ], "identifiers": { "doi": { "normalized": "10.1177/11782234241288671" }, "pmcid": { "normalized": "PMC11528640" }, "pmid": { "normalized": "39493594" } }, "mesh": [], "publication": { "conference_name": null, "date": "2024", "date_precision": "year", "issue": "", "normalized_date": "2024", "pages": "11782234241288671", "proceedings_title": null, "publisher": "", "title": "Breast cancer : basic and clinical research", "volume": "18", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Multicenter Prospective Study in HER2-Positive Early Breast Cancer for Detecting Minimal Residual Disease by Circulating Tumor DNA Analysis With Neoadjuvant Chemotherapy: HARMONY Study.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Selective perturbation of protein interactions with chemical compounds enables dissection and control of developmental processes. Differentiation of stomata, cellular valves vital for plant growth and survival, is specified by the basic-helix-loop-helix (bHLH) heterodimers. Harnessing a new amination reaction, we here report a synthesis, derivatization, target identification, and mode of action of an atypical doubly-sulfonylated imidazolone, Stomidazolone, which triggers stomatal stem cell arrest. Our forward chemical genetics followed by biophysical analyses elucidates that Stomidazolone directly binds to the C-terminal ACT-Like (ACTL) domain of MUTE, a master regulator of stomatal differentiation, and perturbs its heterodimerization with a partner bHLH, SCREAM in vitro and in plant cells. On the other hand, Stomidazolone analogs that are biologically inactive do not bind to MUTE or disrupt the SCREAM-MUTE heterodimers. Guided by structural docking modeling, we rationally design MUTE with reduced Stomidazolone binding. These engineered MUTE proteins are fully functional and confer Stomidazolone resistance in vivo. Our study identifies doubly-sulfonylated imidazolone as a direct inhibitor of the stomatal master regulator, further expanding the chemical space for perturbing bHLH-ACTL proteins to manipulate plant development.", "classifications": [ { "id": "JPMJCR1924", "label": "JPMJCR1924", "researcher": "Yuichiro Tsuchiya", "type": "grant" }, { "id": "Tsuchiya", "label": "Group Tsuchiya", "parent": "Tsuchiya", "type": "group" }, { "id": "Tsuchiya", "label": "Team Tsuchiya", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Ayami", "last_name": "Nakagawa", "name": null }, { "creator_type": "author", "first_name": "Krishna Mohan", "last_name": "Sepuru", "name": null }, { "creator_type": "author", "first_name": "Shu Jan", "last_name": "Yip", "name": null }, { "creator_type": "author", "first_name": "Hyemin", "last_name": "Seo", "name": null }, { "creator_type": "author", "first_name": "Calvin M.", "last_name": "Coffin", "name": null }, { "creator_type": "author", "first_name": "Kota", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Zixuan", "last_name": "Li", "name": null }, { "creator_type": "author", "first_name": "Yasutomo", "last_name": "Segawa", "name": null }, { "creator_type": "author", "first_name": "Rie", "last_name": "Iwasaki", "name": null }, { "creator_type": "author", "first_name": "Hiroe", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Kurihara", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Aihara", "name": null }, { "creator_type": "author", "first_name": "Stephanie", "last_name": "Kim", "name": null }, { "creator_type": "author", "first_name": "Toshinori", "last_name": "Kinoshita", "name": null }, { "creator_type": "author", "first_name": "Kenichiro", "last_name": "Itami", "name": null }, { "creator_type": "author", "first_name": "Soon-Ki", "last_name": "Han", "name": null }, { "creator_type": "author", "first_name": "Kei", "last_name": "Murakami", "name": null }, { "creator_type": "author", "first_name": "Keiko U.", "last_name": "Torii", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41467-024-53214-4" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "39443460" } }, "mesh": [ { "descriptor": "Arabidopsis", "descriptor_ui": "D017360", "major_topic": true }, { "descriptor": "Arabidopsis Proteins", "descriptor_ui": "D029681", "major_topic": true }, { "descriptor": "Basic Helix-Loop-Helix Proteins", "descriptor_ui": "D051792", "major_topic": true }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Gene Expression Regulation, Plant", "descriptor_ui": "D018506", "major_topic": false }, { "descriptor": "Imidazoles", "descriptor_ui": "D007093", "major_topic": false }, { "descriptor": "Molecular Docking Simulation", "descriptor_ui": "D062105", "major_topic": false }, { "descriptor": "Plant Stomata", "descriptor_ui": "D054046", "major_topic": true }, { "descriptor": "Protein Binding", "descriptor_ui": "D011485", "major_topic": false }, { "descriptor": "Protein Domains", "descriptor_ui": "D000072417", "major_topic": false }, { "descriptor": "Protein Multimerization", "descriptor_ui": "D055503", "major_topic": false } ], "publication": { "conference_name": null, "date": "2024", "date_precision": "year", "issue": "", "normalized_date": "2024", "pages": "", "proceedings_title": null, "publisher": "", "title": "Nature Communications", "volume": "15", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Chemical inhibition of stomatal differentiation by perturbation of the master-regulatory bHLH heterodimer via an ACT-Like domain.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Fibrocartilaginous entheses consist of tendons, unmineralized and mineralized fibrocartilage, and subchondral bone, each exhibiting varying stiffness. Here we examined the functional role of sclerostin, expressed in mature mineralized fibrochondrocytes. Following rapid mineralization of unmineralized fibrocartilage and concurrent replacement of epiphyseal hyaline cartilage by bone, unmineralized fibrocartilage reexpanded after a decline in alkaline phosphatase activity at the mineralization front. Sclerostin was co-expressed with osteocalcin at the base of mineralized fibrocartilage adjacent to subchondral bone. In Scx-deficient mice with less mechanical loading due to defects of the Achilles tendon, sclerostin(+) fibrochondrocyte count significantly decreased in the defective enthesis where chondrocyte maturation was markedly impaired in both fibrocartilage and hyaline cartilage. Loss of the Sost gene, encoding sclerostin, elevated mineral density in mineralized zones of fibrocartilaginous entheses. Atomic force microscopy analysis revealed increased fibrocartilage stiffness. These lines of evidence suggest that sclerostin in mature mineralized fibrochondrocytes acts as a modulator for mechanical tissue integrity of fibrocartilaginous entheses.", "classifications": [ { "id": "Maki", "label": "Group Maki", "parent": "Toyoshima", "type": "group" }, { "id": "Toyoshima", "label": "Team Toyoshima", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Shinsei", "last_name": "Yambe", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Yoshimoto", "name": null }, { "creator_type": "author", "first_name": "Kazutaka", "last_name": "Ikeda", "name": null }, { "creator_type": "author", "first_name": "Koichiro", "last_name": "Maki", "name": null }, { "creator_type": "author", "first_name": "Aki", "last_name": "Takimoto", "name": null }, { "creator_type": "author", "first_name": "Akihide", "last_name": "Tokuyama", "name": null }, { "creator_type": "author", "first_name": "Shinnosuke", "last_name": "Higuchi", "name": null }, { "creator_type": "author", "first_name": "Xinyi", "last_name": "Yu", "name": null }, { "creator_type": "author", "first_name": "Kenta", "last_name": "Uchibe", "name": null }, { "creator_type": "author", "first_name": "Shigenori", "last_name": "Miura", "name": null }, { "creator_type": "author", "first_name": "Hitomi", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Tetsushi", "last_name": "Sakuma", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Kotaro", "last_name": "Tanimoto", "name": null }, { "creator_type": "author", "first_name": "Gen", "last_name": "Kondoh", "name": null }, { "creator_type": "author", "first_name": "Masataka", "last_name": "Kasahara", "name": null }, { "creator_type": "author", "first_name": "Toshihide", "last_name": "Mizoguchi", "name": null }, { "creator_type": "author", "first_name": "Denitsa", "last_name": "Docheva", "name": null }, { "creator_type": "author", "first_name": "Taiji", "last_name": "Adachi", "name": null }, { "creator_type": "author", "first_name": "Chisa", "last_name": "Shukunami", "name": null } ], "identifiers": { "doi": { "normalized": "10.3389/fcell.2024.1360041" }, "pmcid": { "normalized": "PMC11183276" }, "pmid": { "normalized": "38895158" } }, "mesh": [], "publication": { "conference_name": null, "date": "2024", "date_precision": "year", "issue": "", "normalized_date": "2024", "pages": "1360041", "proceedings_title": null, "publisher": "", "title": "Frontiers in cell and developmental biology", "volume": "12", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Sclerostin modulates mineralization degree and stiffness profile in the fibrocartilaginous enthesis for mechanical tissue integrity.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: Image and Performance-Enhancing Drugs (IPEDs) can enhance mental and physical capabilities and impact one's overall health. Initially confined in sport environments, IPEDs use has become increasingly widespread in a high-performing society. The present study was aimed at profiling IPEDs use during the COVID-19 lockdown among an international sample of young adults. METHODS: A cross-sectional observational study was carried out in eight countries (United Kingdom, Italy, Lithuania, Hungary, Portugal, Spain, Brazil, and Japan) between April and May 2020. The survey questionnaire included validated measurements such as Exercise Addiction Inventory (EAI), Appearance Anxiety Inventory (AAI), and Self-Compassion Scale (SCS) as well as questions about the type of IPEDs, purchasing methods and socio-demographic information. RESULTS: A total of 736 IPEDs users were included in the survey. Their mean age was 33.05 years (+/-SD = 10.06), and 64.2% were female participants. Overall, 6.8% were found at risk of exercise addiction (EAI >24), 27.6% presented high levels of appearance anxiety, and 24.9% revealed low levels of emotional regulation's self-compassion. Most participants (55.6%) purchased IPEDs through pharmacies/specialized shops, while 41.3% purchased IPEDs on the Internet. Online IPEDs buyers were mainly men who had higher scores on the Exercise Addiction Inventory. One or more IPEDs classifiable as \"potentially risky\" were used by 66.3% of the sample. Users of \"potentially risky IPEDs\" were younger and primarily men. They showed higher scores both on the Exercise Addiction Inventory and Appearance Anxiety Inventory. CONCLUSION: This study profiled users of IPEDs when the most restrictive COVID-19 lockdown policies were implemented in all the participating countries. More targeted post-COVID 19 prevention strategies should be implemented according to the emerged socio-demographic and psychopathological traits and cross-cultural differences emerged. Longitudinal studies will also be needed to determine the long-term effect of the COVID-19 lockdown on IPEDs consumption.", "classifications": [ { "id": "Fujiwara", "label": "Group Fujiwara", "parent": "Fujiwara", "type": "group" }, { "id": "Fujiwara", "label": "Team Fujiwara", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Ilaria", "last_name": "De Luca", "name": null }, { "creator_type": "author", "first_name": "Francesco", "last_name": "Di Carlo", "name": null }, { "creator_type": "author", "first_name": "Julius", "last_name": "Burkauskas", "name": null }, { "creator_type": "author", "first_name": "Artemisa R.", "last_name": "Dores", "name": null }, { "creator_type": "author", "first_name": "Irene P.", "last_name": "Carvalho", "name": null }, { "creator_type": "author", "first_name": "M. Angeles", "last_name": "Gomez-Martinez", "name": null }, { "creator_type": "author", "first_name": "Attila", "last_name": "Szabo", "name": null }, { "creator_type": "author", "first_name": "Hironobu", "last_name": "Fujiwara", "name": null }, { "creator_type": "author", "first_name": "Cristina Monteiro", "last_name": "Barbosa", "name": null }, { "creator_type": "author", "first_name": "Marco", "last_name": "Di Nicola", "name": null }, { "creator_type": "author", "first_name": "Marianna", "last_name": "Mazza", "name": null }, { "creator_type": "author", "first_name": "Gabriele", "last_name": "Sani", "name": null }, { "creator_type": "author", "first_name": "Debora", "last_name": "Luciani", "name": null }, { "creator_type": "author", "first_name": "Mauro", "last_name": "Pettorruso", "name": null }, { "creator_type": "author", "first_name": "Massimo", "last_name": "di Giannantonio", "name": null }, { "creator_type": "author", "first_name": "Ilaria", "last_name": "Cataldo", "name": null }, { "creator_type": "author", "first_name": "Gianluca", "last_name": "Esposito", "name": null }, { "creator_type": "author", "first_name": "Giovanni", "last_name": "Martinotti", "name": null }, { "creator_type": "author", "first_name": "Thomas", "last_name": "Zandonai", "name": null }, { "creator_type": "author", "first_name": "Olivier", "last_name": "Rabin", "name": null }, { "creator_type": "author", "first_name": "Ornella", "last_name": "Corazza", "name": null } ], "identifiers": { "doi": { "normalized": "10.3389/fpubh.2024.1386721" }, "pmcid": { "normalized": "PMC11221326" }, "pmid": { "normalized": "38962770" } }, "mesh": [ { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Behavior, Addictive", "descriptor_ui": "D016739", "major_topic": false }, { "descriptor": "COVID-19", "descriptor_ui": "D000086382", "major_topic": true }, { "descriptor": "Cross-Sectional Studies", "descriptor_ui": "D003430", "major_topic": false }, { "descriptor": "Exercise", "descriptor_ui": "D015444", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Performance-Enhancing Substances", "descriptor_ui": "D058573", "major_topic": true }, { "descriptor": "SARS-CoV-2", "descriptor_ui": "D000086402", "major_topic": false }, { "descriptor": "Substance-Related Disorders", "descriptor_ui": "D019966", "major_topic": false }, { "descriptor": "Surveys and Questionnaires", "descriptor_ui": "D011795", "major_topic": false }, { "descriptor": "Young Adult", "descriptor_ui": "D055815", "major_topic": false } ], "publication": { "conference_name": null, "date": "2024", "date_precision": "year", "issue": "", "normalized_date": "2024", "pages": "1386721", "proceedings_title": null, "publisher": "", "title": "Frontiers in public health", "volume": "12", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Profiling and assessing the risks of image- and performance-enhancing drugs use during the COVID-19 lockdown.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Introduction: RRAS2, a member of the R-Ras subfamily of Ras-like low-molecular-weight GTPases, is considered to regulate cell proliferation and differentiation via the RAS/MAPK signaling pathway. Seven RRAS2 pathogenic variants have been reported in patients with Noonan syndrome; however, few functional analyses have been conducted. Herein, we report two patients who presented with a Noonan-like phenotype with recurrent and novel RRAS2 pathogenic variants (p.Gly23Val and p.Gly24Glu, respectively) and the results of their functional analysis. Materials and methods: Wild-type (WT) and mutant RRAS2 genes were transiently expressed in Human Embryonic Kidney293 cells. Expression of RRAS2 and phosphorylation of ERK1/2 were confirmed by Western blotting, and the RAS signaling pathway activity was measured using a reporter assay system with the serum response element-luciferase construct. WT and p.Gly23Val RRAS2 were expressed in Drosophila eye using the glass multiple reporter-Gal4 driver. Mutant mRNA microinjection into zebrafish embryos was performed, and the embryo jaws were observed. Results: No obvious differences in the expression of proteins WT, p.Gly23Val, and p.Gly24Glu were observed. The luciferase reporter assay showed that the activity of p.Gly23Val was 2.45 ± 0.95-fold higher than WT, and p.Gly24Glu was 3.06 ± 1.35-fold higher than WT. For transgenic flies, the p.Gly23Val expression resulted in no adults flies emerging, indicating lethality. For mutant mRNA-injected zebrafish embryos, an oval shape and delayed jaw development were observed compared with WT mRNA-injected embryos. These indicated hyperactivity of the RAS signaling pathway. Discussion: Recurrent and novel RRAS2 variants that we reported showed increased in vitro or in vivo RAS signaling pathway activity because of gain-of-function RRAS2 variants. Clinical features are similar to those previously reported, suggesting that RRAS2 gain-of-function variants cause this disease in patients.", "classifications": [ { "id": "Suzuki", "label": "Group Suzuki", "parent": "Takekawa", "type": "group" }, { "id": "Takekawa", "label": "Team Takekawa", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Takaya", "last_name": "Iida", "name": null }, { "creator_type": "author", "first_name": "Arisa", "last_name": "Igarashi", "name": null }, { "creator_type": "author", "first_name": "Kae", "last_name": "Fukunaga", "name": null }, { "creator_type": "author", "first_name": "Taiga", "last_name": "Aoki", "name": null }, { "creator_type": "author", "first_name": "Tomomi", "last_name": "Hidai", "name": null }, { "creator_type": "author", "first_name": "Kumiko", "last_name": "Yanagi", "name": null }, { "creator_type": "author", "first_name": "Masahiko", "last_name": "Yamamori", "name": null }, { "creator_type": "author", "first_name": "Kazuhito", "last_name": "Satou", "name": null }, { "creator_type": "author", "first_name": "Hayato", "last_name": "Go", "name": null }, { "creator_type": "author", "first_name": "Tomoki", "last_name": "Kosho", "name": null }, { "creator_type": "author", "first_name": "Ryuto", "last_name": "Maki", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Yohei", "last_name": "Nitta", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Sugie", "name": null }, { "creator_type": "author", "first_name": "Yoichi", "last_name": "Asaoka", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Furutani-Seiki", "name": null }, { "creator_type": "author", "first_name": "Tetsuaki", "last_name": "Kimura", "name": null }, { "creator_type": "author", "first_name": "Yoichi", "last_name": "Matsubara", "name": null }, { "creator_type": "author", "first_name": "Tadashi", "last_name": "Kaname", "name": null } ], "identifiers": { "doi": { "normalized": "10.3389/fgene.2024.1383176" }, "pmcid": { "normalized": "PMC11004488" }, "pmid": { "normalized": "38601074" } }, "mesh": [], "publication": { "conference_name": null, "date": "2024", "date_precision": "year", "issue": "", "normalized_date": "2024", "pages": "1383176", "proceedings_title": null, "publisher": "", "title": "Frontiers in genetics", "volume": "15", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Functional analysis of RRAS2 pathogenic variants with a Noonan-like phenotype.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Flowers exhibit morphological diversity in the number and positional arrangement of their floral organs, such as petals. The petal arrangements of blooming flowers are represented by the overlap position relation between neighboring petals, an indicator of the floral developmental process; however, only specialists are capable of the petal arrangement identification. Therefore, we propose a method to support the estimation of the arrangement of the perianth organs, including petals and tepals, using image recognition techniques. The problem for realizing the method is that it is not possible to prepare a large number of image datasets: we cannot apply the latest machine learning based image processing methods, which require a large number of images. Therefore, we describe the tepal arrangement as a sequence of interior-exterior patterns of tepal overlap in the image, and estimate the tepal arrangement by matching the pattern with the known patterns. We also use methods that require less or no training data to implement the method: the fine-tuned YOLO v5 model for flower detection, GrubCut for flower segmentation, the Harris corner detector for tepal overlap detection, MAML-based interior-exterior estimation, and circular permutation matching for tepal arrangement estimation. Experimental results showed good accuracy when flower detection, segmentation, overlap location estimation, interior-exterior estimation, and circle permutation matching-based tepal arrangement estimation were evaluated independently. However, the accuracy decreased when they were integrated. Therefore, we developed a user interface for manual correction of the position of overlap estimation and interior-exterior pattern estimation, which ensures the quality of tepal arrangement estimation.", "classifications": [ { "id": "Fujimoto", "label": "Group Fujimoto", "parent": "Ueda", "type": "group" }, { "id": "Ueda", "label": "Team Ueda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Tomoya", "last_name": "Nakatani", "name": null }, { "creator_type": "author", "first_name": "Yuzuko", "last_name": "Utsumi", "name": null }, { "creator_type": "author", "first_name": "Koichi", "last_name": "Fujimoto", "name": null }, { "creator_type": "author", "first_name": "Masakazu", "last_name": "Iwamura", "name": null }, { "creator_type": "author", "first_name": "Koichi", "last_name": "Kise", "name": null } ], "identifiers": { "doi": { "normalized": "10.3389/fpls.2024.1334362" }, "pmcid": { "normalized": "PMC11024381" }, "pmid": { "normalized": "38638358" } }, "mesh": [], "publication": { "conference_name": null, "date": "2024", "date_precision": "year", "issue": "", "normalized_date": "2024", "pages": "1334362", "proceedings_title": null, "publisher": "", "title": "Frontiers in plant science", "volume": "15", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Image recognition-based petal arrangement estimation.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "", "classifications": [ { "id": "Onami", "label": "Group Onami", "parent": "Fujiwara", "type": "group" }, { "id": "Fujiwara", "label": "Team Fujiwara", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Kumiko", "last_name": "Hayashi", "name": null }, { "creator_type": "author", "first_name": "Gerhard", "last_name": "Hummer", "name": null }, { "creator_type": "author", "first_name": "Jerelle A.", "last_name": "Joseph", "name": null }, { "creator_type": "author", "first_name": "Rong", "last_name": "Li", "name": null }, { "creator_type": "author", "first_name": "Takeharu", "last_name": "Nagai", "name": null }, { "creator_type": "author", "first_name": "Shuichi", "last_name": "Onami", "name": null }, { "creator_type": "author", "first_name": "Feng", "last_name": "Zhang", "name": null } ], "identifiers": { "doi": { "normalized": "10.2142/biophysico.bppb-v21.e2012" }, "pmcid": { "normalized": "PMC11998096" }, "pmid": { "normalized": "40241780" } }, "mesh": [], "publication": { "conference_name": null, "date": "2024", "date_precision": "year", "issue": "Supplemental2", "normalized_date": "2024", "pages": "e212012", "proceedings_title": null, "publisher": "", "title": "Biophysics and physicobiology", "volume": "21", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "A round table at IUPAB Congress in Kyoto 2024: Dreaming the next 50 years in our biophysics.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: The application of metabolomics-based profiles in environmental epidemiological studies is a promising approach to refine the process of health risk assessment. We aimed to identify potential metabolomics-based profiles in urine and plasma for the detection of relatively low-level cadmium (Cd) exposure in large population-based studies. METHOD: We analyzed 123 urinary metabolites and 94 plasma metabolites detected in fasting urine and plasma samples collected from 1,412 men and 2,022 women involved in the Tsuruoka Metabolomics Cohort Study. Regression analysis was performed for urinary N-acetyl-beta-D-glucosaminidase (NAG), plasma, and urinary metabolites as dependent variables, and urinary Cd (U-Cd, quartile) as an independent variable. The multivariable regression model included age, gender, systolic blood pressure, smoking, rice intake, BMI, glycated hemoglobin, low-density lipoprotein cholesterol, alcohol consumption, physical activity, educational history, dietary energy intake, urinary Na/K ratio, and uric acid. Pathway-network analysis was carried out to visualize the metabolite networks linked to Cd exposure. RESULT: Urinary NAG was positively associated with U-Cd, but not at lower concentrations (Q2). Among urinary metabolites in the total population, 45 metabolites showed associations with U-Cd in the unadjusted and adjusted models after adjusting for the multiplicity of comparison with FDR. There were 12 urinary metabolites which showed consistent associations between Cd exposure from Q2 to Q4. Among plasma metabolites, six cations and one anion were positively associated with U-Cd, whereas alanine, creatinine, and isoleucine were negatively associated with U-Cd. Our results were robust by statistical adjustment of various confounders. Pathway-network analysis revealed metabolites and upstream regulator changes associated with mitochondria (ACACB, UCP2, and metabolites related to the TCA cycle). CONCLUSION: These results suggested that U-Cd was associated with metabolites related to upstream mitochondrial dysfunction in a dose-dependent manner. Our data will help develop environmental Cd exposure profiles for human populations.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yoshiki", "last_name": "Ishibashi", "name": null }, { "creator_type": "author", "first_name": "Sei", "last_name": "Harada", "name": null }, { "creator_type": "author", "first_name": "Yoko", "last_name": "Eitaki", "name": null }, { "creator_type": "author", "first_name": "Ayako", "last_name": "Kurihara", "name": null }, { "creator_type": "author", "first_name": "Suzuka", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Kazuyo", "last_name": "Kuwabara", "name": null }, { "creator_type": "author", "first_name": "Miho", "last_name": "Iida", "name": null }, { "creator_type": "author", "first_name": "Aya", "last_name": "Hirata", "name": null }, { "creator_type": "author", "first_name": "Mizuki", "last_name": "Sata", "name": null }, { "creator_type": "author", "first_name": "Minako", "last_name": "Matsumoto", "name": null }, { "creator_type": "author", "first_name": "Takuma", "last_name": "Shibuki", "name": null }, { "creator_type": "author", "first_name": "Tomonori", "last_name": "Okamura", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Sugiyama", "name": null }, { "creator_type": "author", "first_name": "Asako", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Kaori", "last_name": "Amano", "name": null }, { "creator_type": "author", "first_name": "Akiyoshi", "last_name": "Hirayama", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Sugimoto", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Masaru", "last_name": "Tomita", "name": null }, { "creator_type": "author", "first_name": "Toru", "last_name": "Takebayashi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1265/ehpm.23-00218" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "38556356" } }, "mesh": [ { "descriptor": "Biomarkers", "descriptor_ui": "D015415", "major_topic": false }, { "descriptor": "Cadmium", "descriptor_ui": "D002104", "major_topic": true }, { "descriptor": "Cohort Studies", "descriptor_ui": "D015331", "major_topic": false }, { "descriptor": "Environmental Exposure", "descriptor_ui": "D004781", "major_topic": true }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Kidney", "descriptor_ui": "D007668", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Regression Analysis", "descriptor_ui": "D012044", "major_topic": false } ], "publication": { "conference_name": null, "date": "2024", "date_precision": "year", "issue": "", "normalized_date": "2024", "pages": "22", "proceedings_title": null, "publisher": "", "title": "Environmental health and preventive medicine", "volume": "29", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "A population-based urinary and plasma metabolomics study of environmental exposure to cadmium.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Lenvatinib, a multitarget tyrosine kinase inhibitor for c-Kit and other kinases, has exhibited promising efficacy in treating advanced or metastatic thymic carcinoma (TC). Here, we present the case of a patient with metastatic TC harboring a KIT exon 11 deletion and amplification. The patient exhibited a remarkable response to lenvatinib but experienced rapid disease progression after discontinuation of lenvatinib, referred to as a \"disease flare.\" This case report indicates that KIT mutations and amplification can predict lenvatinib response in patients with TC. However, in such cases, there might be a risk of disease flares after lenvatinib discontinuation.", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Masahiro", "last_name": "Torasawa", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Kouya", "last_name": "Shiraishi", "name": null }, { "creator_type": "author", "first_name": "Naoko", "last_name": "Goto", "name": null }, { "creator_type": "author", "first_name": "Toshihide", "last_name": "Ueno", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Ichikawa", "name": null }, { "creator_type": "author", "first_name": "Shigehiro", "last_name": "Yagishita", "name": null }, { "creator_type": "author", "first_name": "Shinji", "last_name": "Kohsaka", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Goto", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null }, { "creator_type": "author", "first_name": "Akinobu", "last_name": "Hamada", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Mano", "name": null }, { "creator_type": "author", "first_name": "Yuichiro", "last_name": "Ohe", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.jtocrr.2024.100657" }, "pmcid": { "normalized": "PMC11069009" }, "pmid": { "normalized": "38706977" } }, "mesh": [], "publication": { "conference_name": null, "date": "2024 Apr", "date_precision": "unknown", "issue": "4", "normalized_date": null, "pages": "100657", "proceedings_title": null, "publisher": "", "title": "JTO clinical and research reports", "volume": "5", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Rapid Response to Lenvatinib and Disease Flare After Discontinuation in a Patient With Thymic Carcinoma Harboring KIT Exon 11 Mutation: A Case Report.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Cellular functions are realized through the dynamics of chemical reaction networks formed by thousands of chemical reactions. Numerical studies have empirically demonstrated that small differences in network structures among species or tissues can cause substantial changes in dynamics. However, a general principle for behavior changes in response to network structure modifications is not known. The chemical reaction system possesses substructures called buffering structures, which are characterized by a certain topological index being zero. It was proven that the steady-state response to modulation of reaction parameters inside a buffering structure is localized in the buffering structure. In this study, we developed a method to systematically identify the loss or creation of buffering structures induced by the addition of a single degradation reaction from network structure alone. This makes it possible to predict the qualitative and macroscopic changes in regulation that will be caused by the network modification. This method was applied to two reaction systems: the central metabolic system and the mitogen-activated protein kinases signal transduction system. Our method enables identification of reactions that are important for biological functions in living systems.", "classifications": [ { "id": "JPMJCR1922", "label": "JPMJCR1922", "researcher": "Mototsugu Eiraku", "type": "grant" }, { "id": "Eiraku", "label": "Group Eiraku", "parent": "Eiraku", "type": "group" }, { "id": "Mochizuki", "label": "Group Mochizuki", "parent": "Eiraku", "type": "group" }, { "id": "Eiraku", "label": "Team Eiraku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Atsuki", "last_name": "Hishida", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Okada", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Mochizuki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1093/pnasnexus/pgad441" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "38292559" } }, "mesh": [], "publication": { "conference_name": null, "date": "2024 Jan", "date_precision": "unknown", "issue": "1", "normalized_date": null, "pages": "", "proceedings_title": null, "publisher": "", "title": "PNAS Nexus", "volume": "3", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Patterns of change in regulatory modules of chemical reaction systems induced by network modification.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Despite the widespread recognition of the global concern regarding the onset of cardiovascular diseases in a significant number of patients following cancer treatment, definitive strategies for prevention and treatment remain elusive. In this study, we established systems to evaluate the influence of anti-cancer drugs on the quality control of mitochondria, pivotal for energy metabolism, using human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs). Osimertinib, an epidermal growth factor receptor tyrosine kinase inhibitor used for treatment in lung cancer, reportedly increases the risk of cardiovascular disease. However, its underlying mechanism is largely unknown. Here, we found that the treatment of hiPSC-CMs with osimertinib and doxorubicin, but not trastuzumab and cisplatin, revealed a concentration-dependent impairment of respiratory function accompanied by mitochondrial fission. We previously reported the significant role of sulfur metabolism in maintaining mitochondrial quality in the heart. Co-treatment with various inorganic sulfur donors (Na(2)S, Na(2)S(2), Na(2)S(3)) alongside anti-cancer drugs demonstrated that Na(2)S attenuated the cardiotoxicity of osimertinib but not doxorubicin. Osimertinib decreased intracellular reduced sulfur levels, while Na(2)S treatment suppressed the sulfur leakage, suggesting its potential in mitigating osimertinib-induced cardiotoxicity. These results imply the prospect of inorganic sulfides, such as Na(2)S, as a seed for precision pharmacotherapy to alleviate osimertinib's cardiotoxic effects.", "classifications": [ { "id": "JPMJCR2024", "label": "JPMJCR2024", "researcher": "Motohiro Nishida", "type": "grant" }, { "id": "Akaike", "label": "Group Akaike", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Group Nishida", "parent": "Nishida", "type": "group" }, { "id": "Nishimura", "label": "Group Nishimura", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Moe", "last_name": "Kondo", "name": null }, { "creator_type": "author", "first_name": "Yuya", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Yuri", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Akiyuki", "last_name": "Nishimura", "name": null }, { "creator_type": "author", "first_name": "Mitsuhiro", "last_name": "Fukata", "name": null }, { "creator_type": "author", "first_name": "Shohei", "last_name": "Moriyama", "name": null }, { "creator_type": "author", "first_name": "Tomoya", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Keitaro", "last_name": "Umezawa", "name": null }, { "creator_type": "author", "first_name": "Yasuteru", "last_name": "Urano", "name": null }, { "creator_type": "author", "first_name": "Takaaki", "last_name": "Akaike", "name": null }, { "creator_type": "author", "first_name": "Koichi", "last_name": "Akashi", "name": null }, { "creator_type": "author", "first_name": "Yasunari", "last_name": "Kanda", "name": null }, { "creator_type": "author", "first_name": "Motohiro", "last_name": "Nishida", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.jphs.2024.07.007" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "39179336" } }, "mesh": [ { "descriptor": "Acrylamides", "descriptor_ui": "D000178", "major_topic": true }, { "descriptor": "Aniline Compounds", "descriptor_ui": "D000814", "major_topic": true }, { "descriptor": "Antineoplastic Agents", "descriptor_ui": "D000970", "major_topic": true }, { "descriptor": "Cardiotoxicity", "descriptor_ui": "D066126", "major_topic": false }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Doxorubicin", "descriptor_ui": "D004317", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Indoles", "descriptor_ui": "D007211", "major_topic": false }, { "descriptor": "Induced Pluripotent Stem Cells", "descriptor_ui": "D057026", "major_topic": true }, { "descriptor": "Mitochondria", "descriptor_ui": "D008928", "major_topic": true }, { "descriptor": "Mitochondrial Dynamics", "descriptor_ui": "D063154", "major_topic": false }, { "descriptor": "Myocytes, Cardiac", "descriptor_ui": "D032383", "major_topic": true }, { "descriptor": "Pyrimidines", "descriptor_ui": "D011743", "major_topic": false }, { "descriptor": "Sulfides", "descriptor_ui": "D013440", "major_topic": true }, { "descriptor": "Sulfur", "descriptor_ui": "D013455", "major_topic": false } ], "publication": { "conference_name": null, "date": "2024 Oct", "date_precision": "unknown", "issue": "2", "normalized_date": null, "pages": "69-76", "proceedings_title": null, "publisher": "", "title": "Journal of pharmacological sciences", "volume": "156", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Inorganic sulfides prevent osimertinib-induced mitochondrial dysfunction in human iPS cell-derived cardiomyocytes.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND/AIM: (18)F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) is reportedly associated with the malignant potential of cancer. This study aimed to evaluate the association between FDG accumulation and tumor metabolism in pancreatic ductal adenocarcinoma (PDAC). PATIENTS AND METHODS: A prognostic analysis of data from 131 patients with PDAC who underwent FDG-PET/CT before curative-intent pancreatic surgery was performed. Capillary electrophoresis-mass spectrometry (CE-MS) was used to analyze the metabolome of tumor and non-neoplastic pancreas from 80 patients. These patients were divided into two groups: low SUVmax group (SUVmax <6.09) and high SUVmax group (SUVmax >/=6.09). RESULTS: Carbohydrate antigen 19-9 (CA19-9), maximum standardized uptake value (SUVmax) of PET, N stage, and postoperative chemotherapy were identified as significant prognostic factors by univariate analysis. SUVmax emerged as an independent prognostic factor for overall survival [hazard ratio (HR)=1.88, p<0.05] and disease-free survival (HR=2.01, p<0.05) in multivariate analysis. Metabolic analyses confirmed that 43 metabolites significantly differed depending on the accumulation of SUV in tumors. Metabolites involved in the removal of reactive oxygen species (e.g., hypotaurine, glutathione, Met), treatment resistance (UDP-N-acetylglucosamine), and proliferation (e.g., choline, leucine, isoleucine) were increased in the high SUVmax group. CONCLUSION: FDG accumulation is an important independent prognostic factor reflecting tumor activity associated with metabolic changes in cancer cells.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Ayaka", "last_name": "Shimomura", "name": null }, { "creator_type": "author", "first_name": "Minoru", "last_name": "Oshima", "name": null }, { "creator_type": "author", "first_name": "Hironobu", "last_name": "Suto", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Matsukawa", "name": null }, { "creator_type": "author", "first_name": "Akihiro", "last_name": "Kondo", "name": null }, { "creator_type": "author", "first_name": "Yasuhisa", "last_name": "Ando", "name": null }, { "creator_type": "author", "first_name": "Takayoshi", "last_name": "Kishino", "name": null }, { "creator_type": "author", "first_name": "Kensuke", "last_name": "Kumamoto", "name": null }, { "creator_type": "author", "first_name": "Kiyotoshi", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Sugimoto", "name": null }, { "creator_type": "author", "first_name": "Mina", "last_name": "Nagao", "name": null }, { "creator_type": "author", "first_name": "Nobuyuki", "last_name": "Miyatake", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Norikane", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Keiichi", "last_name": "Okano", "name": null } ], "identifiers": { "doi": { "normalized": "10.21873/anticanres.17151" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "39060044" } }, "mesh": [ { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Aged, 80 and over", "descriptor_ui": "D000369", "major_topic": false }, { "descriptor": "Carcinoma, Pancreatic Ductal", "descriptor_ui": "D021441", "major_topic": true }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Fluorodeoxyglucose F18", "descriptor_ui": "D019788", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Pancreatic Neoplasms", "descriptor_ui": "D010190", "major_topic": true }, { "descriptor": "Positron Emission Tomography Computed Tomography", "descriptor_ui": "D000072078", "major_topic": true }, { "descriptor": "Prognosis", "descriptor_ui": "D011379", "major_topic": false }, { "descriptor": "Radiopharmaceuticals", "descriptor_ui": "D019275", "major_topic": false } ], "publication": { "conference_name": null, "date": "2024 Aug", "date_precision": "unknown", "issue": "8", "normalized_date": null, "pages": "3321-3330", "proceedings_title": null, "publisher": "", "title": "Anticancer research", "volume": "44", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Prognostic Significance of (18)F-FDG PET/CT and Tumor Metabolic Changes in Patients With Pancreatic Ductal Adenocarcinoma.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Zebrafish is a useful model organism in neuroscience; however, its gene expression atlas in the adult brain is not well developed. In the present study, we examined the expression of 38 neuropeptides, comparing with GABAergic and glutamatergic neuron marker genes in the adult zebrafish brain by comprehensive in situ hybridization. The results are summarized as an expression atlas in 19 coronal planes of the forebrain. Furthermore, the scanned data of all brain sections were made publicly available in the Adult Zebrafish Brain Gene Expression Database (https://ssbd.riken.jp/azebex/). Based on these data, we performed detailed comparative neuroanatomical analyses of the hypothalamus and found that several regions previously described as one nucleus in the reference zebrafish brain atlas contain two or more subregions with significantly different neuropeptide/neurotransmitter expression profiles. Subsequently, we compared the expression data in zebrafish telencephalon and hypothalamus obtained in this study with those in mice, by performing a cluster analysis. As a result, several nuclei in zebrafish and mice were clustered in close vicinity. The present expression atlas, database, and anatomical findings will contribute to future neuroscience research using zebrafish.", "classifications": [ { "id": "Onami", "label": "Group Onami", "parent": "Fujiwara", "type": "group" }, { "id": "Fujiwara", "label": "Team Fujiwara", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Towako", "last_name": "Hiraki-Kajiyama", "name": null }, { "creator_type": "author", "first_name": "Nobuhiko", "last_name": "Miyasaka", "name": null }, { "creator_type": "author", "first_name": "Reiko", "last_name": "Ando", "name": null }, { "creator_type": "author", "first_name": "Noriko", "last_name": "Wakisaka", "name": null }, { "creator_type": "author", "first_name": "Hiroya", "last_name": "Itoga", "name": null }, { "creator_type": "author", "first_name": "Shuichi", "last_name": "Onami", "name": null }, { "creator_type": "author", "first_name": "Yoshihiro", "last_name": "Yoshihara", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/cne.25619" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "38831653" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Atlases as Topic", "descriptor_ui": "D001271", "major_topic": false }, { "descriptor": "Databases, Genetic", "descriptor_ui": "D030541", "major_topic": false }, { "descriptor": "Gene Expression", "descriptor_ui": "D015870", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Neuropeptides", "descriptor_ui": "D009479", "major_topic": true }, { "descriptor": "Prosencephalon", "descriptor_ui": "D016548", "major_topic": true }, { "descriptor": "Zebrafish", "descriptor_ui": "D015027", "major_topic": true } ], "publication": { "conference_name": null, "date": "2024 Jun", "date_precision": "unknown", "issue": "6", "normalized_date": null, "pages": "e25619", "proceedings_title": null, "publisher": "", "title": "The Journal of comparative neurology", "volume": "532", "year": 2024 }, "ssbd": { "database": [], "repository": [ "ssbd-repos-000266" ] }, "title": "An atlas and database of neuropeptide gene expression in the adult zebrafish forebrain.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "We derive generalized Langevin equations (GLEs) for single beads in linear elastic networks. In particular, the derivations of the GLEs are conducted without employing normal modes, resulting in two distinct representations in terms of resistance and mobility kernels. The fluctuation-dissipation relations are also confirmed for both GLEs. Subsequently, we demonstrate that these two representations are interconnected via Laplace transforms. Furthermore, another GLE is derived by utilizing a projection operator method, and it is shown that the equation obtained through the projection scheme is consistent with the GLE with the resistance kernel. As simple examples, the general theory is applied to the Rouse model and the ring polymer, where the GLEs with the resistance and mobility kernels are explicitly derived for arbitrary positions of the tagged bead in these models. Finally, the GLE with the mobility kernel is also derived for the elastic network with hydrodynamic interactions under the pre-averaging approximation.", "classifications": [ { "id": "Onami", "label": "Group Onami", "parent": "Fujiwara", "type": "group" }, { "id": "Fujiwara", "label": "Team Fujiwara", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Soya", "last_name": "Shinkai", "name": null }, { "creator_type": "author", "first_name": "Shuichi", "last_name": "Onami", "name": null }, { "creator_type": "author", "first_name": "Tomoshige", "last_name": "Miyaguchi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1103/physreve.110.044136" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "39562923" } }, "mesh": [], "publication": { "conference_name": null, "date": "2024 Oct", "date_precision": "unknown", "issue": "4-1", "normalized_date": null, "pages": "044136", "proceedings_title": null, "publisher": "", "title": "Physical review. E", "volume": "110", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Generalized Langevin dynamics for single beads in linear elastic networks.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "We investigate the convergence of chemical reaction networks (CRNs), aiming to establish an upper bound on their reaction rates. The nonlinear characteristics and discrete composition of CRNs pose significant challenges in this endeavor. To circumvent these complexities, we adopt an information geometric perspective, utilizing the natural gradient to formulate a nonlinear system. This system effectively determines an upper bound for the dynamics of CRNs. We corroborate our methodology through numerical simulations, which reveal that our constructed system converges more rapidly than CRNs within a particular class of reactions. This class is defined by the count of chemicals, the highest stoichiometric coefficients in the reactions, and the total number of reactions involved. Further, we juxtapose our approach with traditional methods, illustrating that the latter falls short in providing an upper bound for CRN reaction rates. Although our investigation centers on CRNs, the widespread presence of hypergraphs across various disciplines, ranging from natural sciences to engineering, indicates potential wider applications of our method, including in the realm of information science.", "classifications": [ { "id": "JPMJCR1927", "label": "JPMJCR1927", "researcher": "Yuichi Wakamoto", "type": "grant" }, { "id": "Kobayashi", "label": "Group Kobayashi", "parent": "Wakamoto", "type": "group" }, { "id": "Wakamoto", "label": "Group Wakamoto", "parent": "Wakamoto", "type": "group" }, { "id": "Wakamoto", "label": "Team Wakamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Tsuyoshi", "last_name": "Mizohata", "name": null }, { "creator_type": "author", "first_name": "Tetsuya J.", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Louis-S.", "last_name": "Bouchard", "name": null }, { "creator_type": "author", "first_name": "Hideyuki", "last_name": "Miyahara", "name": null } ], "identifiers": { "doi": { "normalized": "10.1103/physreve.109.044308" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "38755923" } }, "mesh": [], "publication": { "conference_name": null, "date": "2024 Apr", "date_precision": "unknown", "issue": "4-1", "normalized_date": null, "pages": "044308", "proceedings_title": null, "publisher": "", "title": "Physical review. E", "volume": "109", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Information geometric bound on general chemical reaction networks.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Patients with coronavirus disease 2019 (COVID-19) pneumonia are prone to intrapulmonary thrombosis owing to excessive inflammation and platelet activation. Myelodysplastic/myeloproliferative neoplasm (MDS/MPN) with ring sideroblasts and thrombocytosis (RS-T) is a rare disease in MDS/MPN overlap entities. Patients with MDS/MPN RS-T are known to be at a high risk of thrombosis, and platelet count control with drug therapy does not necessarily reduce this risk. Here, we report the autopsy case of an older male patient with MDS/MPN RS-T and severe COVID-19 pneumonia complicated by intrapulmonary thrombosis. His platelet count had been controlled in the normal range after treatment with hydroxyurea and 5-aza-2'-deoxycytidine. On admission day, he rapidly developed respiratory distress and tested positive on a polymerase chain reaction test for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). After admission, he received supplemental oxygen and was administered remdesivir and dexamethasone; however, his respiratory and circulatory status did not improve. The patient died on day 4 of illness. Autopsy findings revealed massive thrombi within blood vessels and diffuse alveolar damage in both lungs, which were determined to be the cause of death. In patients with MDS/MPN RS-T combined with COVID-19 pneumonia, clinicians may need to pay close attention to the risk of pulmonary thrombosis.", "classifications": [ { "id": "Tanaka", "label": "Group Tanaka", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yoshinori", "last_name": "Harada", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Makino", "name": null }, { "creator_type": "author", "first_name": "Ryuta", "last_name": "Nakao", "name": null }, { "creator_type": "author", "first_name": "Yuji", "last_name": "Shimura", "name": null }, { "creator_type": "author", "first_name": "Takehiro", "last_name": "Ogata", "name": null }, { "creator_type": "author", "first_name": "Michiyo", "last_name": "Hayakawa", "name": null }, { "creator_type": "author", "first_name": "Hirokazu", "last_name": "Shiraishi", "name": null }, { "creator_type": "author", "first_name": "Junya", "last_name": "Kuroda", "name": null }, { "creator_type": "author", "first_name": "Satoaki", "last_name": "Matoba", "name": null }, { "creator_type": "author", "first_name": "Hideo", "last_name": "Tanaka", "name": null } ], "identifiers": { "doi": { "normalized": "10.7759/cureus.62790" }, "pmcid": { "normalized": "PMC11260265" }, "pmid": { "normalized": "39036222" } }, "mesh": [], "publication": { "conference_name": null, "date": "2024 Jun", "date_precision": "unknown", "issue": "6", "normalized_date": null, "pages": "e62790", "proceedings_title": null, "publisher": "", "title": "Cureus", "volume": "16", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "An Autopsy Case of Severe COVID-19 Pneumonia Complicated by Intrapulmonary Thrombosis in Myelodysplastic/Myeloproliferative Neoplasm With Ring Sideroblasts and Thrombocytosis.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Cell–cell adhesion regulates multicellular patterning in stratified epithelia, with starvation-induced adherens junctions forming high/low cell density areas, affecting differentiation and proliferation via Yes-associated protein modulation, highlighting epithelial cells’ self-organizing properties.", "classifications": [ { "id": "JPMJCR1926", "label": "JPMJCR1926", "researcher": "Hironobu Fujiwara", "type": "grant" }, { "id": "Fujiwara", "label": "Group Fujiwara", "parent": "Fujiwara", "type": "group" }, { "id": "Nagayama", "label": "Group Nagayama", "parent": "Fujiwara", "type": "group" }, { "id": "Fujiwara", "label": "Team Fujiwara", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yosuke", "last_name": "Mai", "name": null }, { "creator_type": "author", "first_name": "Yasuaki", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Kitahata", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Seo", "name": null }, { "creator_type": "author", "first_name": "Takuma", "last_name": "Nohara", "name": null }, { "creator_type": "author", "first_name": "Sota", "last_name": "Itamoto", "name": null }, { "creator_type": "author", "first_name": "Shoko", "last_name": "Mai", "name": null }, { "creator_type": "author", "first_name": "Junichi", "last_name": "Kumamoto", "name": null }, { "creator_type": "author", "first_name": "Masaharu", "last_name": "Nagayama", "name": null }, { "creator_type": "author", "first_name": "Wataru", "last_name": "Nishie", "name": null }, { "creator_type": "author", "first_name": "Hideyuki", "last_name": "Ujiie", "name": null }, { "creator_type": "author", "first_name": "Ken", "last_name": "Natsuga", "name": null } ], "identifiers": { "doi": { "normalized": "10.26508/lsa.202402893" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "39025524" } }, "mesh": [ { "descriptor": "Adherens Junctions", "descriptor_ui": "D022005", "major_topic": true }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Adhesion", "descriptor_ui": "D002448", "major_topic": true }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": true }, { "descriptor": "Cell Proliferation", "descriptor_ui": "D049109", "major_topic": true }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Epithelial Cells", "descriptor_ui": "D004847", "major_topic": true }, { "descriptor": "Epithelium", "descriptor_ui": "D004848", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Keratinocytes", "descriptor_ui": "D015603", "major_topic": true }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false } ], "publication": { "conference_name": null, "date": "2024 Sep", "date_precision": "unknown", "issue": "9", "normalized_date": null, "pages": "", "proceedings_title": null, "publisher": "", "title": "Life Science Alliance", "volume": "7", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Patterning in stratified epithelia depends on cell–cell adhesion.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Smoking is one of the most serious risk factors for cardiovascular diseases. Although cigarette mainstream and sidestream smoke are significant contributors to increased cardiovascular mortality and morbidity, the underlying mechanism is still unclear. Here, we report that exposure of rat neonatal cardiomyocytes to cigarette smoke extract (CSE) induces mitochondrial hyperfission-mediated myocardial senescence. CSE leads to mitochondrial fission and reactive oxygen species (ROS) production through the complex formation between mitochondrial fission factor Drp1 and actin-binding protein, filamin A. Pharmacological perturbation of interaction between Drp1 and filamin A by cilnidipine and gene knockdown of Drp1 or filamin A inhibited CSE-induced mitochondrial hyperfission and ROS production as well as myocardial senescence. We previously reported that Drp1 activity is controlled by supersulfide-induced Cys644 polysulfidation. The redox-sensitive Cys644 was critical for CSE-mediated interaction with filamin A. The administration of supersulfide donor, Na(2)S(3) also improved mitochondrial hyperfission-mediated myocardial senescence induced by CSE. Our results suggest the important role of Drp1-filamin A complex formation on cigarette smoke-mediated cardiac risk and the contribution of supersulfide to mitochondrial fission-associated myocardial senescence.", "classifications": [ { "id": "JPMJCR2024", "label": "JPMJCR2024", "researcher": "Motohiro Nishida", "type": "grant" }, { "id": "Nishida", "label": "Group Nishida", "parent": "Nishida", "type": "group" }, { "id": "Nishimura", "label": "Group Nishimura", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Akiyuki", "last_name": "Nishimura", "name": null }, { "creator_type": "author", "first_name": "Liuchenzi", "last_name": "Zhou", "name": null }, { "creator_type": "author", "first_name": "Yuri", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Xinya", "last_name": "Mi", "name": null }, { "creator_type": "author", "first_name": "Tomoya", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Yuko", "last_name": "Ibuki", "name": null }, { "creator_type": "author", "first_name": "Yasunari", "last_name": "Kanda", "name": null }, { "creator_type": "author", "first_name": "Motohiro", "last_name": "Nishida", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.jphs.2023.12.008" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "38246726" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cigarette Smoking", "descriptor_ui": "D000073865", "major_topic": true }, { "descriptor": "Filamins", "descriptor_ui": "D064448", "major_topic": false }, { "descriptor": "Mitochondria", "descriptor_ui": "D008928", "major_topic": false }, { "descriptor": "Myocytes, Cardiac", "descriptor_ui": "D032383", "major_topic": true }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Reactive Oxygen Species", "descriptor_ui": "D017382", "major_topic": false }, { "descriptor": "Sulfides", "descriptor_ui": "D013440", "major_topic": false } ], "publication": { "conference_name": null, "date": "2024 Feb", "date_precision": "unknown", "issue": "2", "normalized_date": null, "pages": "127-135", "proceedings_title": null, "publisher": "", "title": "Journal of pharmacological sciences", "volume": "154", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Supersulfide prevents cigarette smoke extract-induced mitochondria hyperfission and cardiomyocyte early senescence by inhibiting Drp1-filamin complex formation.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "PURPOSE: The clinical application of PD-L1 immunohistochemistry (IHC) testing is complicated by the availability of multiple IHC assays, scoring algorithms, and cutoffs. This study assessed the analytical comparability of three commercially available PD-L1 assays and two scoring algorithms used to assess PD-L1 status in gastric cancer (GC) samples. METHODS: Serial sections of 100 resected GC samples, with PD-L1 expression levels across the dynamic range, were stained with three in vitro diagnostic-grade PD-L1 assays (28-8, 22C3, and SP263). Three trained pathologists blindly and independently scored slides using combined positive score (CPS) and tumor area positivity (TAP) algorithms. Comprehensive statistical analyses were performed to evaluate analytical concordance. Digital image analysis (DIA) was used to objectively compare the technical performance of each assay by simulating CPS and TAP. RESULTS: Comparable staining patterns were observed with these three PD-L1 assays. Despite discernible variation in staining intensity, reproducible evaluations of PD-L1 positivity were observed. Inter- and intra-assay assessments of all three assays, using either CPS or TAP and the same PD-L1 cutoffs, demonstrated moderate to almost-perfect (interassay Cohen's kappa [kappa] range, 0.47-0.83) and substantial to almost-perfect (intra-assay kappa range, 0.77-1.00) agreement. Interpathologist assessment exhibited a significant level of concordance (intraclass correlation coefficient >/=0.92). No difference in technical performance was observed using DIA. CONCLUSION: This study highlights analytical concordance in PD-L1 testing between three major PD-L1 assays when TAP and CPS are applied. Comparability of the technical assay performance was further supported by independent DIA. These observations support cross-application flexibility of the different PD-L1 assays and scoring algorithms to characterize PD-L1 expression in GC.", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Samuel J.", "last_name": "Klempner", "name": null }, { "creator_type": "author", "first_name": "Eric S.", "last_name": "Cowden", "name": null }, { "creator_type": "author", "first_name": "Samuel L.", "last_name": "Cytryn", "name": null }, { "creator_type": "author", "first_name": "Matteo", "last_name": "Fassan", "name": null }, { "creator_type": "author", "first_name": "Hisato", "last_name": "Kawakami", "name": null }, { "creator_type": "author", "first_name": "Hideaki", "last_name": "Shimada", "name": null }, { "creator_type": "author", "first_name": "Laura H.", "last_name": "Tang", "name": null }, { "creator_type": "author", "first_name": "Daniel-Christoph", "last_name": "Wagner", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null }, { "creator_type": "author", "first_name": "Alexander", "last_name": "Savchenko", "name": null }, { "creator_type": "author", "first_name": "Jennifer", "last_name": "Salcius", "name": null }, { "creator_type": "author", "first_name": "Dorhyun", "last_name": "Johng", "name": null }, { "creator_type": "author", "first_name": "Jing", "last_name": "Chen", "name": null }, { "creator_type": "author", "first_name": "Giuliana", "last_name": "Montenegro", "name": null }, { "creator_type": "author", "first_name": "Markus", "last_name": "Moehler", "name": null } ], "identifiers": { "doi": { "normalized": "10.1200/po.24.00230" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "38822761" } }, "mesh": [ { "descriptor": "Algorithms", "descriptor_ui": "D000465", "major_topic": false }, { "descriptor": "B7-H1 Antigen", "descriptor_ui": "D060890", "major_topic": true }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Immunohistochemistry", "descriptor_ui": "D007150", "major_topic": true }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Stomach Neoplasms", "descriptor_ui": "D013274", "major_topic": true } ], "publication": { "conference_name": null, "date": "2024 Jun", "date_precision": "unknown", "issue": "", "normalized_date": null, "pages": "e2400230", "proceedings_title": null, "publisher": "", "title": "JCO precision oncology", "volume": "8", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "PD-L1 Immunohistochemistry in Gastric Cancer: Comparison of Combined Positive Score and Tumor Area Positivity Across 28-8, 22C3, and SP263 Assays.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "OBJECTIVE: Oncological feasibility of segmentectomy for internal non-small cell lung cancer (NSCLC) has not been assessed adequately. We assessed the oncological feasibility of segmentectomy for inner-located NSCLC by investigating surgical margins and patient prognosis after undergoing the procedure. METHODS: Of the 3555 patients who underwent resection for lung cancer between 2013 and 2019 at our institution, 659 patients who underwent segmentectomy for clinical stage 0 to stage1A NSCLC were included in this study. Patients were separated into 2 groups according to whether the tumor was in the inner or outer third of the lung area. Clinical characteristics and prognoses were retrospectively compared between the groups. RESULTS: Of the included 659 cases, 183 (27.8%) were inner-located, and 476 (72.2%) had outer-located NSCLC. The surgical margin was significantly shorter in the inner-located group than in the outer group (median, 16 vs 25 mm; P < .001). The 5-year recurrence-free survival and overall survival probabilities were 91.1%/91.8% (P = .530) and 94.1%/95.6% (P = .345) for inner/outer-located groups, respectively. Multivariate analysis showed that clinical stage IA2 or 3 (P = .043), lymphovascular invasion (P < .001), and surgical margins <20 mm (P = .017) were independent prognostic factors for recurrence-free survival. The location of the inner or outer tumors was not related to the prognosis. CONCLUSIONS: For clinical stage 0 to stage1A NSCLC, tumor location in the inner two-thirds of the lung was not associated with prognosis after segmentectomy. Because one of the independent prognostic factors is margin distance, segmentectomy for inner-located NSCLC would be oncologically acceptable when an adequate surgical margin is secured.", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Kaito", "last_name": "Yano", "name": null }, { "creator_type": "author", "first_name": "Masaya", "last_name": "Yotsukura", "name": null }, { "creator_type": "author", "first_name": "Hirokazu", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Takaki", "last_name": "Akamine", "name": null }, { "creator_type": "author", "first_name": "Yukihiro", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Kazuo", "last_name": "Nakagawa", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null }, { "creator_type": "author", "first_name": "Masahiko", "last_name": "Kusumoto", "name": null }, { "creator_type": "author", "first_name": "Shun-Ichi", "last_name": "Watanabe", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.xjon.2024.02.015" }, "pmcid": { "normalized": "PMC11056493" }, "pmid": { "normalized": "38690420" } }, "mesh": [], "publication": { "conference_name": null, "date": "2024 Apr", "date_precision": "unknown", "issue": "", "normalized_date": null, "pages": "261-275", "proceedings_title": null, "publisher": "", "title": "JTCVS open", "volume": "18", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Oncological feasibility of segmentectomy for inner-located lung cancer.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "In this PRO-CON debate, you will read very different perspectives about a simple question regarding an observation under the microscope: What is the significance of tumor cells in the air spaces of the lung parenchyma beyond the tumor edge of a resected lung cancer? An important underlying question is whether this entire PRO-CON debate is a mere academic exercise or whether spread through air spaces (STAS), as currently defined, describes a clinically useful phenomenon. The journey of STAS began with a complete paradigm shift to reverse the thinking that all air space tumor cells beyond the edge of lung cancers are an artifact. This led to a new concept where STAS could be separated from artifacts with a definition that has proven to be clinically useful. As with any major change in thinking, it is understandable that there would be some disagreement with this paradigm shift. Nevertheless, after a decade since it was described, many pathologists and clinicians around the world have found STAS to provide important information about the behavior of lung cancer. Numerous PRO-STAS articles supporting the usefulness of STAS have been published with clinical data on many thousands of patients from numerous institutions all over the world. In contrast, for the CON-STAS articles, widespread international representation and data are limited. It is now difficult to ignore the numerous reports and is reasonable to consider how to use the presence of STAS in clinical decisions. Hopefully, this PRO-CON debate will further stimulate clinical and scientific investigations aimed at a better understanding of STAS.", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yan", "last_name": "Li", "name": null }, { "creator_type": "author", "first_name": "Prasad S.", "last_name": "Adusumilli", "name": null }, { "creator_type": "author", "first_name": "Teh-Ying", "last_name": "Chou", "name": null }, { "creator_type": "author", "first_name": "Kyuichi", "last_name": "Kadota", "name": null }, { "creator_type": "author", "first_name": "Mari", "last_name": "Mino-Kenudson", "name": null }, { "creator_type": "author", "first_name": "Mauro", "last_name": "Papotti", "name": null }, { "creator_type": "author", "first_name": "Natasha", "last_name": "Rekhtman", "name": null }, { "creator_type": "author", "first_name": "Yukako", "last_name": "Yagi", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null }, { "creator_type": "author", "first_name": "William D.", "last_name": "Travis", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.jtho.2024.03.001" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "38719424" } }, "mesh": [ { "descriptor": "Artifacts", "descriptor_ui": "D016477", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Lung Neoplasms", "descriptor_ui": "D008175", "major_topic": true } ], "publication": { "conference_name": null, "date": "2024 May", "date_precision": "unknown", "issue": "5", "normalized_date": null, "pages": "677-697", "proceedings_title": null, "publisher": "", "title": "Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer", "volume": "19", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Pro: \"Is Spread Through Air Spaces an In Vivo Phenomenon or an Inducible Artifact?\".", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Eukaryotic cells perform chemotaxis by determining the direction of chemical gradients based on stochastic sensing of concentrations at the cell surface. To examine the efficiency of this process, previous studies have investigated the limit of estimation accuracy for gradients. However, most studies have treated a circular cell shape, and the few considering elongated shapes assume the elongated direction as fixed. This leaves the question of how adaptive regulation of cell shape affects the estimation limit. Dynamics of cell shape during gradient sensing is biologically ubiquitous and can influence the estimation by altering the way the concentration is measured, and cells may strategically regulate their shape to improve estimation accuracy. To address this gap, we investigate the estimation limits in dynamic situations where elongated cells change their orientation adaptively depending on the sensed signal. We approach this problem by analyzing the stationary solution of the Bayesian nonlinear filtering equation. By applying diffusion approximation to the ligand-receptor binding process and the Laplace method for the posterior expectation under a high signal-to-noise ratio regime, we obtain an analytical expression for the estimation limit. This expression indicates that estimation accuracy can be improved by aligning the elongated direction perpendicular to the estimated direction, which is also confirmed by numerical simulations. Our analysis provides a basis for clarifying the interplay between estimation and control in gradient sensing and sheds light on how cells optimize their shape to enhance chemotactic efficiency.", "classifications": [ { "id": "Kobayashi", "label": "Group Kobayashi", "parent": "Wakamoto", "type": "group" }, { "id": "Wakamoto", "label": "Team Wakamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Kento", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Tetsuya J.", "last_name": "Kobayashi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1103/physreve.110.064407" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "39916211" } }, "mesh": [ { "descriptor": "Bayes Theorem", "descriptor_ui": "D001499", "major_topic": false }, { "descriptor": "Cell Shape", "descriptor_ui": "D048430", "major_topic": true }, { "descriptor": "Chemotaxis", "descriptor_ui": "D002633", "major_topic": true }, { "descriptor": "Diffusion", "descriptor_ui": "D004058", "major_topic": false }, { "descriptor": "Models, Biological", "descriptor_ui": "D008954", "major_topic": true }, { "descriptor": "Signal-To-Noise Ratio", "descriptor_ui": "D059629", "major_topic": false }, { "descriptor": "Stochastic Processes", "descriptor_ui": "D013269", "major_topic": false } ], "publication": { "conference_name": null, "date": "2024 Dec", "date_precision": "unknown", "issue": "6-1", "normalized_date": null, "pages": "064407", "proceedings_title": null, "publisher": "", "title": "Physical review. E", "volume": "110", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Gradient sensing limit of an elongated cell with orientational control.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The transcriptional coactivator Yes-associated protein (YAP)/transcriptional co-activator with PDZ binding motif (TAZ) induces cell proliferation through nuclear localization at low cell density. Conversely, at extremely high cell density, the Hippo pathway, which regulates YAP/TAZ, is activated. This activation leads to the translocation of YAP/TAZ into the cytoplasm, resulting in cell cycle arrest. Various cancer cells have several times more YAP/TAZ than normal cells. However, it is not entirely clear whether this several-fold increase in YAP/TAZ alone is sufficient to overcome proliferation inhibition (contact inhibition) under high-density conditions, thereby allowing continuous proliferation. In this study, we construct a three-dimensional (3D) mathematical model of cell proliferation incorporating the Hippo-YAP/TAZ pathway. Herein, a significant innovation in our approach is the introduction of a novel modeling component that inputs cell density, which reflects cell dynamics, into the Hippo pathway and enables the simulation of cell proliferation as the output response. We assume such 3D model with cell-cell interactions by solving reaction and molecular dynamics (MD) equations by applying adhesion and repulsive forces that act between cells and frictional forces acting on each cell. We assume Lennard-Jones (12-6) potential with a softcore character so that each cell secures its exclusive domain. We set cell cycles composed of mitotic and cell growth phases in which cells divide and grow under the influence of cell kinetics. We perform mathematical simulations at various YAP/TAZ levels to investigate the extent of YAP/TAZ increase required for sustained proliferation at high density. The results show that a twofold increase in YAP/TAZ levels of cancer cells was sufficient to evade cell cycle arrest compared to normal cells, enabling cells to continue proliferating even under high-density conditions. Finally, this mathematical model, which incorporates cell-cell interactions and the Hippo-YAP/TAZ pathway, may be applicable for evaluating cancer malignancy based on YAP/TAZ levels, developing drugs to suppress the abnormal proliferation of cancer cells, and determining appropriate drug dosages. The source codes are freely available.", "classifications": [ { "id": "JPMJCR2022", "label": "JPMJCR2022", "researcher": "Mutsuhiro Takekawa", "type": "grant" }, { "id": "Suzuki", "label": "Group Suzuki", "parent": "Takekawa", "type": "group" }, { "id": "Takekawa", "label": "Group Takekawa", "parent": "Takekawa", "type": "group" }, { "id": "Takekawa", "label": "Team Takekawa", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Toshihito", "last_name": "Umegaki", "name": null }, { "creator_type": "author", "first_name": "Hisashi", "last_name": "Moriizumi", "name": null }, { "creator_type": "author", "first_name": "Fumiko", "last_name": "Ogushi", "name": null }, { "creator_type": "author", "first_name": "Mutsuhiro", "last_name": "Takekawa", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Suzuki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1371/journal.pcbi.1012536" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "39527559" } }, "mesh": [ { "descriptor": "Adaptor Proteins, Signal Transducing", "descriptor_ui": "D048868", "major_topic": false }, { "descriptor": "Cell Communication", "descriptor_ui": "D002450", "major_topic": true }, { "descriptor": "Cell Proliferation", "descriptor_ui": "D049109", "major_topic": true }, { "descriptor": "Hippo Signaling Pathway", "descriptor_ui": "D000090683", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Models, Biological", "descriptor_ui": "D008954", "major_topic": false }, { "descriptor": "Molecular Dynamics Simulation", "descriptor_ui": "D056004", "major_topic": true }, { "descriptor": "Protein Serine-Threonine Kinases", "descriptor_ui": "D017346", "major_topic": true }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": true }, { "descriptor": "Transcription Factors", "descriptor_ui": "D014157", "major_topic": true }, { "descriptor": "YAP-Signaling Proteins", "descriptor_ui": "D000091102", "major_topic": false } ], "publication": { "conference_name": null, "date": "2024 Nov", "date_precision": "unknown", "issue": "11", "normalized_date": null, "pages": "e1012536", "proceedings_title": null, "publisher": "", "title": "PLoS computational biology", "volume": "20", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Molecular dynamics simulations of a multicellular model with cell-cell interactions and Hippo signaling pathway.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: The three-item Sexual Distress Scale (SDS-3) has been frequently used to assess distress related to sexuality in public health surveys and research on sexual wellbeing. However, its psychometric properties and measurement invariance across cultural, gender and sexual subgroups have not yet been examined. This multinational study aimed to validate the SDS-3 and test its psychometric properties, including measurement invariance across language, country, gender identity, and sexual orientation groups. METHODS: We used global survey data from 82,243 individuals (Mean (age)=32.39 years; 40.3 % men, 57.0 % women, 2.8 % non-binary, and 0.6 % other genders) participating in the International Sexual Survey (ISS; https://internationalsexsurvey.org/) across 42 countries and 26 languages. Participants completed the SDS-3, as well as questions regarding sociodemographic characteristics, including gender identity and sexual orientation. RESULTS: Confirmatory factor analysis (CFA) supported a unidimensional factor structure for the SDS-3, and multi-group CFA (MGCFA) suggested that this factor structure was invariant across countries, languages, gender identities, and sexual orientations. Cronbach's alpha for the unidimensional score was 0.83 (range between 0.76 and 0.89), and McDonald's omega was 0.84 (range between 0.76 and 0.90). Participants who did not experience sexual problems had significantly lower SDS-3 total scores (M = 2.99; SD=2.54) compared to those who reported sexual problems (M = 5.60; SD=3.00), with a large effect size (Cohen's d = 1.01 [95 % CI=-1.03, -0.98]; p < 0.001). CONCLUSION: The SDS-3 has a unidimensional factor structure and appears to be valid and reliable for measuring sexual distress among individuals from different countries, gender identities, and sexual orientations.", "classifications": [ { "id": "Fujiwara", "label": "Group Fujiwara", "parent": "Fujiwara", "type": "group" }, { "id": "Fujiwara", "label": "Team Fujiwara", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Chung-Ying", "last_name": "Lin", "name": null }, { "creator_type": "author", "first_name": "Meng-Che", "last_name": "Tsai", "name": null }, { "creator_type": "author", "first_name": "Monika", "last_name": "Koos", "name": null }, { "creator_type": "author", "first_name": "Lena", "last_name": "Nagy", "name": null }, { "creator_type": "author", "first_name": "Shane W.", "last_name": "Kraus", "name": null }, { "creator_type": "author", "first_name": "Zsolt", "last_name": "Demetrovics", "name": null }, { "creator_type": "author", "first_name": "Marc N.", "last_name": "Potenza", "name": null }, { "creator_type": "author", "first_name": "Rafael", "last_name": "Ballester-Arnal", "name": null }, { "creator_type": "author", "first_name": "Dominik", "last_name": "Batthyany", "name": null }, { "creator_type": "author", "first_name": "Sophie", "last_name": "Bergeron", "name": null }, { "creator_type": "author", "first_name": "Joel", "last_name": "Billieux", "name": null }, { "creator_type": "author", "first_name": "Peer", "last_name": "Briken", "name": null }, { "creator_type": "author", "first_name": "Georgina", "last_name": "Cardenas-Lopez", "name": null }, { "creator_type": "author", "first_name": "Joana", "last_name": "Carvalho", "name": null }, { "creator_type": "author", "first_name": "Jesus", "last_name": "Castro-Calvo", "name": null }, { "creator_type": "author", "first_name": "Lijun", "last_name": "Chen", "name": null }, { "creator_type": "author", "first_name": "Giacomo", "last_name": "Ciocca", "name": null }, { "creator_type": "author", "first_name": "Ornella", "last_name": "Corazza", "name": null }, { "creator_type": "author", "first_name": "Rita I.", "last_name": "Csako", "name": null }, { "creator_type": "author", "first_name": "David P.", "last_name": "Fernandez", "name": null }, { "creator_type": "author", "first_name": "Elaine F.", "last_name": "Fernandez", "name": null }, { "creator_type": "author", "first_name": "Hironobu", "last_name": "Fujiwara", "name": null }, { "creator_type": "author", "first_name": "Johannes", "last_name": "Fuss", "name": null }, { "creator_type": "author", "first_name": "Roman", "last_name": "Gabrhelik", "name": null }, { "creator_type": "author", "first_name": "Ateret", "last_name": "Gewirtz-Meydan", "name": null }, { "creator_type": "author", "first_name": "Biljana", "last_name": "Gjoneska", "name": null }, { "creator_type": "author", "first_name": "Mateusz", "last_name": "Gola", "name": null }, { "creator_type": "author", "first_name": "Joshua B.", "last_name": "Grubbs", "name": null }, { "creator_type": "author", "first_name": "Hashim T.", "last_name": "Hashim", "name": null }, { "creator_type": "author", "first_name": "Md Saiful", "last_name": "Islam", "name": null }, { "creator_type": "author", "first_name": "Mustafa", "last_name": "Ismail", "name": null }, { "creator_type": "author", "first_name": "Martha", "last_name": "Jimenez-Martinez", "name": null }, { "creator_type": "author", "first_name": "Tanja", "last_name": "Jurin", "name": null }, { "creator_type": "author", "first_name": "Ondrej", "last_name": "Kalina", "name": null }, { "creator_type": "author", "first_name": "Verena", "last_name": "Klein", "name": null }, { "creator_type": "author", "first_name": "Andras", "last_name": "Kolto", "name": null }, { "creator_type": "author", "first_name": "Sang-Kyu", "last_name": "Lee", "name": null }, { "creator_type": "author", "first_name": "Karol", "last_name": "Lewczuk", "name": null }, { "creator_type": "author", "first_name": "Christine", "last_name": "Lochner", "name": null }, { "creator_type": "author", "first_name": "Silvia", "last_name": "Lopez-Alvarado", "name": null }, { "creator_type": "author", "first_name": "Katerina", "last_name": "Lukavska", "name": null }, { "creator_type": "author", "first_name": "Percy", "last_name": "Mayta-Tristan", "name": null }, { "creator_type": "author", "first_name": "Ion", "last_name": "Milea", "name": null }, { "creator_type": "author", "first_name": "Dan J.", "last_name": "Miller", "name": null }, { "creator_type": "author", "first_name": "Olga", "last_name": "Orosova", "name": null }, { "creator_type": "author", "first_name": "Gabor", "last_name": "Orosz", "name": null }, { "creator_type": "author", "first_name": "Fernando P.", "last_name": "Ponce", "name": null }, { "creator_type": "author", "first_name": "Gonzalo R.", "last_name": "Quintana", "name": null }, { "creator_type": "author", "first_name": "Gabriel C. Quintero", "last_name": "Garzola", "name": null }, { "creator_type": "author", "first_name": "Jano", "last_name": "Ramos-Diaz", "name": null }, { "creator_type": "author", "first_name": "Kevin", "last_name": "Rigaud", "name": null }, { "creator_type": "author", "first_name": "Ann", "last_name": "Rousseau", "name": null }, { "creator_type": "author", "first_name": "Marco De Tubino", "last_name": "Scanavino", "name": null }, { "creator_type": "author", "first_name": "Marion K.", "last_name": "Schulmeyer", "name": null }, { "creator_type": "author", "first_name": "Pratap", "last_name": "Sharan", "name": null }, { "creator_type": "author", "first_name": "Mami", "last_name": "Shibata", "name": null }, { "creator_type": "author", "first_name": "Sheikh", "last_name": "Shoib", "name": null }, { "creator_type": "author", "first_name": "Vera", "last_name": "Sigre-Leiros", "name": null }, { "creator_type": "author", "first_name": "Luke", "last_name": "Sniewski", "name": null }, { "creator_type": "author", "first_name": "Ognen", "last_name": "Spasovski", "name": null }, { "creator_type": "author", "first_name": "Vesta", "last_name": "Steibliene", "name": null }, { "creator_type": "author", "first_name": "Dan J.", "last_name": "Stein", "name": null }, { "creator_type": "author", "first_name": "Julian", "last_name": "Strizek", "name": null }, { "creator_type": "author", "first_name": "Aleksandar", "last_name": "Stulhofer", "name": null }, { "creator_type": "author", "first_name": "Berk C.", "last_name": "Unsal", "name": null }, { "creator_type": "author", "first_name": "Marie-Pier", "last_name": "Vaillancourt-Morel", "name": null }, { "creator_type": "author", "first_name": "Marie Claire", "last_name": "Van Hout", "name": null }, { "creator_type": "author", "first_name": "Beata", "last_name": "Bothe", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.ijchp.2024.100461" }, "pmcid": { "normalized": "PMC11067538" }, "pmid": { "normalized": "38706570" } }, "mesh": [], "publication": { "conference_name": null, "date": "2024 Apr-Jun", "date_precision": "unknown", "issue": "2", "normalized_date": null, "pages": "100461", "proceedings_title": null, "publisher": "", "title": "International journal of clinical and health psychology : IJCHP", "volume": "24", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "The short version of the Sexual Distress Scale (SDS-3): Measurement invariance across countries, gender identities, and sexual orientations.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The atrophic myocardium resulting from mechanical unloading and nutritional deprivation is considered crucial as maladaptive remodeling directly associated with heart failure, as well as interstitial fibrosis. Conversely, myocardial hypertrophy resulting from hemodynamic loading is perceived as compensatory stress adaptation. We previously reported the abundant presence of highly redox-active polysulfide molecules, termed supersulfide, with two or more sulfur atoms catenated in normal hearts, and the supersulfide catabolism in pathologic hearts after myocardial infarction correlated with worsened prognosis of heart failure. However, the impact of supersulfide on myocardial remodeling remains unclear. Here, we investigated the involvement of supersulfide metabolism in cardiomyocyte remodeling, using a model of adenosine 5'-triphosphate (ATP) receptor-stimulated atrophy and endothelin-1 receptor-stimulated hypertrophy in neonatal rat cardiomyocytes. Results revealed contrasting changes in intracellular supersulfide and its catabolite, hydrogen sulfide (H(2)S), between cardiomyocyte atrophy and hypertrophy. Stimulation of cardiomyocytes with ATP decreased supersulfide activity, while H(2)S accumulation itself did not affect cardiomyocyte atrophy. This supersulfide catabolism was also involved in myofibroblast formation of neonatal rat cardiac fibroblasts. Thus, unraveling supersulfide metabolism during myocardial remodeling may lead to the development of novel therapeutic strategies to improve heart failure.", "classifications": [ { "id": "JPMJCR2024", "label": "JPMJCR2024", "researcher": "Motohiro Nishida", "type": "grant" }, { "id": "Akaike", "label": "Group Akaike", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Group Nishida", "parent": "Nishida", "type": "group" }, { "id": "Nishimura", "label": "Group Nishimura", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Liuchenzi", "last_name": "Zhou", "name": null }, { "creator_type": "author", "first_name": "Akiyuki", "last_name": "Nishimura", "name": null }, { "creator_type": "author", "first_name": "Keitaro", "last_name": "Umezawa", "name": null }, { "creator_type": "author", "first_name": "Yuri", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Xinya", "last_name": "Mi", "name": null }, { "creator_type": "author", "first_name": "Tomoya", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Yasuteru", "last_name": "Urano", "name": null }, { "creator_type": "author", "first_name": "Takaaki", "last_name": "Akaike", "name": null }, { "creator_type": "author", "first_name": "Motohiro", "last_name": "Nishida", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.jphs.2024.05.002" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "38880546" } }, "mesh": [ { "descriptor": "Adenosine Triphosphate", "descriptor_ui": "D000255", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Animals, Newborn", "descriptor_ui": "D000831", "major_topic": false }, { "descriptor": "Atrophy", "descriptor_ui": "D001284", "major_topic": false }, { "descriptor": "Cardiomegaly", "descriptor_ui": "D006332", "major_topic": false }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Heart Failure", "descriptor_ui": "D006333", "major_topic": false }, { "descriptor": "Hydrogen Sulfide", "descriptor_ui": "D006862", "major_topic": true }, { "descriptor": "Myocytes, Cardiac", "descriptor_ui": "D032383", "major_topic": true }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Rats, Sprague-Dawley", "descriptor_ui": "D017207", "major_topic": false }, { "descriptor": "Sulfides", "descriptor_ui": "D013440", "major_topic": true }, { "descriptor": "Ventricular Remodeling", "descriptor_ui": "D020257", "major_topic": true } ], "publication": { "conference_name": null, "date": "2024 Aug", "date_precision": "unknown", "issue": "4", "normalized_date": null, "pages": "121-130", "proceedings_title": null, "publisher": "", "title": "Journal of pharmacological sciences", "volume": "155", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Supersulfide catabolism participates in maladaptive remodeling of cardiac cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Vision is formed by the transmission of light stimuli to the brain through axons extending from photoreceptor cells. Damage to these axons leads to loss of vision. Despite research on neural circuit regeneration through transplantation, achieving precise axon projection remains challenging. To achieve optic nerve regeneration by transplantation, we employed the Drosophila visual system. We previously established a transplantation method for Drosophila utilizing photoreceptor precursor cells extracted from the eye disc. However, little axonal elongation of transplanted cells into the brain, the lamina, was observed. We verified axonal elongation to the lamina by modifying the selection process for transplanted cells. Moreover, we focused on N-cadherin (Ncad), a cell adhesion factor, and Twinstar (Tsr), which has been shown to promote actin reorganization and induce axon elongation in damaged nerves. Overexpression of Ncad and tsr promoted axon elongation to the lamina, along with presynaptic structure formation in the elongating axons. Furthermore, overexpression of Neurexin-1 (Nrx-1), encoding a protein identified as a synaptic organizer, was found to not only promote presynapse formation but also enhance axon elongation. By introducing Ncad, tsr, and Nrx-1, we not only successfully achieved axonal projection of transplanted cells to the brain beyond the retina, but also confirmed the projection of transplanted cells into a deeper ganglion, the medulla. The present study offers valuable insights to realize regeneration through transplantation in a more complex nervous system.", "classifications": [ { "id": "Suzuki", "label": "Group Suzuki", "parent": "Takekawa", "type": "group" }, { "id": "Takekawa", "label": "Team Takekawa", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Riku", "last_name": "Iwanaga", "name": null }, { "creator_type": "author", "first_name": "Nagisa", "last_name": "Yahagi", "name": null }, { "creator_type": "author", "first_name": "Satoko", "last_name": "Hakeda-Suzuki", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Suzuki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/dgd.12916" }, "pmcid": { "normalized": "PMC11457513" }, "pmid": { "normalized": "38403285" } }, "mesh": [ { "descriptor": "Actins", "descriptor_ui": "D000199", "major_topic": true }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Axons", "descriptor_ui": "D001369", "major_topic": false }, { "descriptor": "Cell Adhesion", "descriptor_ui": "D002448", "major_topic": true }, { "descriptor": "Drosophila", "descriptor_ui": "D004330", "major_topic": true }, { "descriptor": "Photoreceptor Cells", "descriptor_ui": "D010786", "major_topic": true }, { "descriptor": "Synapses", "descriptor_ui": "D013569", "major_topic": false } ], "publication": { "conference_name": null, "date": "2024 Apr", "date_precision": "unknown", "issue": "3", "normalized_date": null, "pages": "205-218", "proceedings_title": null, "publisher": "", "title": "Development, growth & differentiation", "volume": "66", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Cell adhesion and actin dynamics factors promote axonal extension and synapse formation in transplanted Drosophila photoreceptor cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Heterotopic ossification (HO) is a non-physiological bone formation where soft tissue progenitor cells differentiate into chondrogenic cells. In fibrodysplasia ossificans progressiva (FOP), a rare genetic disease characterized by progressive and systemic HO, the Activin A/mutated ACVR1/mTORC1 cascade induces HO in progenitors in muscle tissues. The relevant biological processes aberrantly regulated by activated mTORC1 remain unclear, however. RNA-sequencing analyses revealed the enrichment of genes involved in oxidative phosphorylation (OXPHOS) during Activin A-induced chondrogenesis of mesenchymal stem cells derived from FOP patient-specific induced pluripotent stem cells. Functional analyses showed a metabolic transition from glycolysis to OXPHOS during chondrogenesis, along with increased mitochondrial biogenesis. mTORC1 inhibition by rapamycin suppressed OXPHOS, whereas OXPHOS inhibitor IACS-010759 inhibited cartilage matrix formation in vitro, indicating that OXPHOS is principally involved in mTORC1-induced chondrogenesis. Furthermore, IACS-010759 inhibited the muscle injury-induced enrichment of fibro/adipogenic progenitor genes and HO in transgenic mice carrying the mutated human ACVR1. These data indicated that OXPHOS is a critical downstream mediator of mTORC1 signaling in chondrogenesis and therefore is a potential FOP therapeutic target.", "classifications": [ { "id": "Yamamoto", "label": "Group Yamamoto", "parent": "Toyoshima", "type": "group" }, { "id": "Toyoshima", "label": "Team Toyoshima", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Liping", "last_name": "Sun", "name": null }, { "creator_type": "author", "first_name": "Yonghui", "last_name": "Jin", "name": null }, { "creator_type": "author", "first_name": "Megumi", "last_name": "Nishio", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Kamakura", "name": null }, { "creator_type": "author", "first_name": "Sanae", "last_name": "Nagata", "name": null }, { "creator_type": "author", "first_name": "Masayuki", "last_name": "Fukuda", "name": null }, { "creator_type": "author", "first_name": "Hirotsugu", "last_name": "Maekawa", "name": null }, { "creator_type": "author", "first_name": "Shunsuke", "last_name": "Kawai", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Junya", "last_name": "Toguchida", "name": null } ], "identifiers": { "doi": { "normalized": "10.26508/lsa.202302219" }, "pmcid": { "normalized": "PMC10875110" }, "pmid": { "normalized": "38365425" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mechanistic Target of Rapamycin Complex 1", "descriptor_ui": "D000076222", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Transgenic", "descriptor_ui": "D008822", "major_topic": false }, { "descriptor": "Myositis Ossificans", "descriptor_ui": "D009221", "major_topic": true }, { "descriptor": "Ossification, Heterotopic", "descriptor_ui": "D009999", "major_topic": true }, { "descriptor": "Oxidative Phosphorylation", "descriptor_ui": "D010085", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false } ], "publication": { "conference_name": null, "date": "2024 May", "date_precision": "unknown", "issue": "5", "normalized_date": null, "pages": "", "proceedings_title": null, "publisher": "", "title": "Life science alliance", "volume": "7", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Oxidative phosphorylation is a pivotal therapeutic target of fibrodysplasia ossificans progressiva.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Achievement of treatment-free remission (TFR) after tyrosine kinase inhibitor (TKI) discontinuation in patients who show a durable deep molecular response (DMR) during TKI treatment of chronic myeloid leukemia in chronic phase (CML-CP) is a therapeutic goal; however, the prognostic factors that predict successful achievement of TFR are unclear. Previously, we reported that killer immunoglobulin-like receptor (KIR) and HLA polymorphisms are associated with achievement of a DMR. Here, we investigated the association between KIR and HLA polymorphisms and TFR. We conducted the POKSTIC (POlymorphisms of Killer immunoglobulin-like receptor, which affect Stop Tyrosine kinase Inhibitor in patients with Chronic myeloid leukemia) trial, a multicenter collaborative observational study that enrolled 76 patients with CML-CP. The median age was 63 years (interquartile range [IQR], 49-70). Of 76 patients, 42 (56.6%; 95% confidence interval [CI], 47.7-66.8 at 6 months) discontinued TKIs without molecular relapse; the median follow-up time for TFR was 24 months (IQR, 16-64). KIR genotyping and allele typing did not identify risk factors for molecular relapse; however, univariate and multivariate analysis identified the combination of KIR3DL1-HLA-Bw4 (an HLA-B allele) as an independent factor for a higher risk of molecular relapse (hazard ratio, 2.206; 95% CI, 1.112-4.376; P = .024). Notably, patients at higher risk of relapse had a significantly lower number of natural killer (NK) cells at TKI discontinuation than the other patients (CD16(+)/CD56(+) NK cells: median 499.63 cells per muL vs 629.17 cells per muL, respectively; P = .049). Thus, KIR3DL1-HLA-Bw status reflects NK cell responses and is associated with TFR. The study is registered with the UMIN Clinical Trials Registry as #UMIN000041798.", "classifications": [ { "id": "Tanaka", "label": "Group Tanaka", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Ureshino", "name": null }, { "creator_type": "author", "first_name": "Yasunori", "last_name": "Ueda", "name": null }, { "creator_type": "author", "first_name": "Shin", "last_name": "Fujisawa", "name": null }, { "creator_type": "author", "first_name": "Kensuke", "last_name": "Usuki", "name": null }, { "creator_type": "author", "first_name": "Hideo", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Masaya", "last_name": "Okada", "name": null }, { "creator_type": "author", "first_name": "Shugo", "last_name": "Kowata", "name": null }, { "creator_type": "author", "first_name": "Kazunori", "last_name": "Murai", "name": null }, { "creator_type": "author", "first_name": "Asao", "last_name": "Hirose", "name": null }, { "creator_type": "author", "first_name": "Motohiro", "last_name": "Shindo", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Kumagai", "name": null }, { "creator_type": "author", "first_name": "Tomoharu", "last_name": "Takeoka", "name": null }, { "creator_type": "author", "first_name": "Kazuharu", "last_name": "Kamachi", "name": null }, { "creator_type": "author", "first_name": "Keisuke", "last_name": "Kidoguchi", "name": null }, { "creator_type": "author", "first_name": "Takero", "last_name": "Shindo", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Iyama", "name": null }, { "creator_type": "author", "first_name": "Junki", "last_name": "Inamura", "name": null }, { "creator_type": "author", "first_name": "Takafumi", "last_name": "Nakao", "name": null }, { "creator_type": "author", "first_name": "Tsutomu", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Eri", "last_name": "Kawata", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Ohkawara", "name": null }, { "creator_type": "author", "first_name": "Takayuki", "last_name": "Ikezoe", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Kawaguchi", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Kimura", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.bneo.2024.100001" }, "pmcid": { "normalized": "PMC12082104" }, "pmid": { "normalized": "40453521" } }, "mesh": [], "publication": { "conference_name": null, "date": "2024 Mar", "date_precision": "unknown", "issue": "1", "normalized_date": null, "pages": "100001", "proceedings_title": null, "publisher": "", "title": "Blood neoplasia", "volume": "1", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "KIR3DL1-HLA-Bw status in CML is associated with achievement of TFR: the POKSTIC trial, a multicenter observational study.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Given that esophageal cancer is highly malignant, the discovery of novel prognostic markers is eagerly awaited. We performed serological identification of antigens by recombinant cDNA expression cloning (SEREX) and identified SKI proto-oncogene protein and transmembrane p24 trafficking protein 5 (TMED5) as antigens recognized by serum IgG antibodies in patients with esophageal carcinoma. SKI and TMED5 proteins were expressed in Escherichia coli, purified by affinity chromatography, and used as antigens. The serum anti-SKI antibody (s-SKI-Ab) and anti-TMED5 antibody (s-TMED5-Ab) levels were significantly higher in 192 patients with esophageal carcinoma than in 96 healthy donors. The presence of s-SKI-Abs and s-TMED5-Abs in the patients' sera was confirmed by western blotting. Immunohistochemical staining showed that the TMED5 protein was highly expressed in the cytoplasm and nuclear compartments of the esophageal squamous cell carcinoma tissues, whereas the SKI protein was localized predominantly in the nuclei. Regarding the overall survival in 91 patients who underwent radical surgery, the s-SKI-Ab-positive and s-TMED5-Ab-negative statuses were significantly associated with a favorable prognosis. Additionally, the combination of s-SKI-Ab-positive and s-TMED5-Ab-negative cases showed an even clearer difference in overall survival as compared with that of s-SKI-Ab-negative and s-TMED5-Ab-positive cases. The s-SKI-Ab and s-TMED5-Ab biomarkers are useful for diagnosing esophageal carcinoma and distinguishing between favorable and poor prognoses.", "classifications": [ { "id": "Suzuki", "label": "Group Suzuki", "parent": "Takekawa", "type": "group" }, { "id": "Takekawa", "label": "Team Takekawa", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Masaaki", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Yajima", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Yoko", "last_name": "Oshima", "name": null }, { "creator_type": "author", "first_name": "Tatsuki", "last_name": "Nanami", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Sumazaki", "name": null }, { "creator_type": "author", "first_name": "Fumiaki", "last_name": "Shiratori", "name": null }, { "creator_type": "author", "first_name": "Hirotaka", "last_name": "Takizawa", "name": null }, { "creator_type": "author", "first_name": "Shu-Yang", "last_name": "Li", "name": null }, { "creator_type": "author", "first_name": "Bo-Shi", "last_name": "Zhang", "name": null }, { "creator_type": "author", "first_name": "Yoichi", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Tomoo", "last_name": "Matsutani", "name": null }, { "creator_type": "author", "first_name": "Takaki", "last_name": "Hiwasa", "name": null }, { "creator_type": "author", "first_name": "Hideaki", "last_name": "Shimada", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/cas.16185" }, "pmcid": { "normalized": "PMC11247554" }, "pmid": { "normalized": "38634426" } }, "mesh": [ { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Aged, 80 and over", "descriptor_ui": "D000369", "major_topic": false }, { "descriptor": "Biomarkers, Tumor", "descriptor_ui": "D014408", "major_topic": true }, { "descriptor": "Carcinoma, Squamous Cell", "descriptor_ui": "D002294", "major_topic": false }, { "descriptor": "DNA-Binding Proteins", "descriptor_ui": "D004268", "major_topic": false }, { "descriptor": "Esophageal Neoplasms", "descriptor_ui": "D004938", "major_topic": true }, { "descriptor": "Esophageal Squamous Cell Carcinoma", "descriptor_ui": "D000077277", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Membrane Proteins", "descriptor_ui": "D008565", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Prognosis", "descriptor_ui": "D011379", "major_topic": false }, { "descriptor": "Proto-Oncogene Mas", "descriptor_ui": "D000090063", "major_topic": true }, { "descriptor": "Proto-Oncogene Proteins", "descriptor_ui": "D011518", "major_topic": true } ], "publication": { "conference_name": null, "date": "2024 Jul", "date_precision": "unknown", "issue": "7", "normalized_date": null, "pages": "2209-2219", "proceedings_title": null, "publisher": "", "title": "Cancer science", "volume": "115", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Combination of high anti-SKI and low anti-TMED5 antibody levels is preferable prognostic factor in esophageal carcinoma.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The spatiotemporal dynamics of inflammation provide vital insights into the understanding of skin inflammation. Skin inflammation primarily depends on the regulatory feedback between pro- and anti-inflammatory mediators. Healthy skin exhibits fading erythema. In contrast, diseased skin exhibits expanding erythema with diverse patterns, which are clinically classified into five types: circular, annular, arcuate, gyrate, and polycyclic. Inflammatory diseases with expanding erythema are speculated to result from the overproduction of pro-inflammatory mediators. However, the mechanism by which feedback selectively drives the transition from a healthy fading erythema to each of the five types of diseased expanding erythema remains unclear. This study theoretically elucidates the imbalanced production between pro- and anti-inflammatory mediators and prospective treatment strategies for each expanding pattern. Our literature survey showed that eleven diseases exhibit some of the five expanding erythema, thereby suggesting a common spatiotemporal regulation underlying different patterns and diseases. Accordingly, a reaction-diffusion model incorporating mediator feedback reproduced the five observed types of diseased expanding and healthy fading patterns. Importantly, the fading pattern transitioned to the arcuate, gyrate, and polycyclic patterns when the productions of anti-inflammatory and pro-inflammatory mediators were lower and higher, respectively than in the healthy condition. Further depletion of anti-inflammatory mediators caused a circular pattern, whereas further overproduction of pro-inflammatory mediators caused an annular pattern. Mechanistically, the bistability due to stabilization of the diseased state exhibits circular and annular patterns, whereas the excitability exhibits the gyrate, polycyclic, arcuate, and fading patterns as the threshold of pro-inflammatory mediator concentration relative to the healthy state increases. These dynamic regulations of diffusive mediator feedback provide effective treatment strategies for mediator production wherein skins recover from each expanding pattern toward a fading pattern. Thus, these strategies can estimate disease severity and risk based on erythema patterns, paving the way for developing noninvasive and personalized treatments for inflammatory skin diseases.", "classifications": [ { "id": "JPMJCR2121", "label": "JPMJCR2121", "researcher": "Minako Ueda", "type": "grant" }, { "id": "Fujimoto", "label": "Group Fujimoto", "parent": "Ueda", "type": "group" }, { "id": "Ueda", "label": "Group Ueda", "parent": "Ueda", "type": "group" }, { "id": "Ueda", "label": "Team Ueda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Maki", "last_name": "Sudo", "name": null }, { "creator_type": "author", "first_name": "Koichi", "last_name": "Fujimoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1371/journal.pcbi.1011693" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "38236792" } }, "mesh": [ { "descriptor": "Erythema", "descriptor_ui": "D004890", "major_topic": true }, { "descriptor": "Feedback", "descriptor_ui": "D005246", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Inflammation", "descriptor_ui": "D007249", "major_topic": false }, { "descriptor": "Inflammation Mediators", "descriptor_ui": "D018836", "major_topic": false }, { "descriptor": "Skin", "descriptor_ui": "D012867", "major_topic": true } ], "publication": { "conference_name": null, "date": "2024 Jan", "date_precision": "unknown", "issue": "1", "normalized_date": null, "pages": "", "proceedings_title": null, "publisher": "", "title": "PLOS Computational Biology", "volume": "20", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Diffusive mediator feedbacks control the health-to-disease transition of skin inflammation.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Sulfur-based redox signaling has long attracted attention as critical mechanisms underlying the development of cardiac diseases and resultant heart failure. Especially, post-translational modifications of cysteine (Cys) thiols in proteins mediate oxidative stress-dependent cardiac remodeling including myocardial hypertrophy, senescence, and interstitial fibrosis. However, we recently revealed the existence of Cys persulfides and Cys polysulfides in cells and tissues, which show higher redox activities than Cys and substantially contribute to redox signaling and energy metabolism. We have established simple evaluation methods that can detect polysulfides in proteins and inorganic polysulfides in cells and revealed that polysulfides abundantly expressed in normal hearts are dramatically catabolized by exposure to ischemic/hypoxic and environmental electrophilic stress, which causes vulnerability of the heart to mechanical load. Accumulation of hydrogen sulfide, a nucleophilic catabolite of persulfides/polysulfides, may lead to reductive stress in ischemic hearts, and perturbation of polysulfide catabolism can improve chronic heart failure after myocardial infarction in mice. This review focuses on the (patho)physiological role of sulfur metabolism in hearts, and proposes that sulfur catabolism during ischemic/hypoxic stress has great potential as a new therapeutic strategy for the treatment of ischemic heart failure.", "classifications": [ { "id": "JPMJCR2024", "label": "JPMJCR2024", "researcher": "Motohiro Nishida", "type": "grant" }, { "id": "Nishida", "label": "Group Nishida", "parent": "Nishida", "type": "group" }, { "id": "Nishimura", "label": "Group Nishimura", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Akiyuki", "last_name": "Nishimura", "name": null }, { "creator_type": "author", "first_name": "Xiaokang", "last_name": "Tang", "name": null }, { "creator_type": "author", "first_name": "Liuchenzi", "last_name": "Zhou", "name": null }, { "creator_type": "author", "first_name": "Tomoya", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Yuri", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Motohiro", "last_name": "Nishida", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.jphs.2024.04.005" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "38797536" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cysteine", "descriptor_ui": "D003545", "major_topic": true }, { "descriptor": "Energy Metabolism", "descriptor_ui": "D004734", "major_topic": false }, { "descriptor": "Heart Failure", "descriptor_ui": "D006333", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Hydrogen Sulfide", "descriptor_ui": "D006862", "major_topic": true }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Molecular Targeted Therapy", "descriptor_ui": "D058990", "major_topic": false }, { "descriptor": "Myocardium", "descriptor_ui": "D009206", "major_topic": false }, { "descriptor": "Oxidation-Reduction", "descriptor_ui": "D010084", "major_topic": true }, { "descriptor": "Oxidative Stress", "descriptor_ui": "D018384", "major_topic": false }, { "descriptor": "Protein Processing, Post-Translational", "descriptor_ui": "D011499", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Sulfides", "descriptor_ui": "D013440", "major_topic": true }, { "descriptor": "Sulfur", "descriptor_ui": "D013455", "major_topic": true } ], "publication": { "conference_name": null, "date": "2024 Jul", "date_precision": "unknown", "issue": "3", "normalized_date": null, "pages": "75-83", "proceedings_title": null, "publisher": "", "title": "Journal of pharmacological sciences", "volume": "155", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Sulfur metabolism as a new therapeutic target of heart failure.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Objectives: Disruption of the oxidative stress defense system is involved in developing various diseases. Sulfur compounds such as glutathione (GSH) and cysteine (CysSH) are representative antioxidants in the body. Recently, supersulfides, including reactive persulfide and polysulfide species, have gained attention as potent antioxidants regulating oxidative stress and redox signaling. However, their involvement in the pathogenesis of chronic rhinosinusitis (CRS) remains unclear. Methods: To clarify the changes in sulfur compounds within the sinus mucosa of each CRS subtype, we measured sulfur compound levels in the sinus mucosa of control individuals (n = 9), patients with eosinophilic CRS (ECRS) (n = 13), and those with non‐ECRS (nECRS) (n = 11) who underwent sinus surgery using mass spectrometry. Results: GSH and CysSH levels were significantly reduced, and the glutathione disulfide (GSSG)/GSH ratio, an oxidative stress indicator, was increased in patients with ECRS. Despite the absence of notable variations in supersulfides, patients with ECRS and nECRS exhibited a significant reduction in glutathione trisulfide (GSSSG), which serves as the precursor for supersulfides. Conclusions: This study is the first quantitative assessment of supersulfides in normal and inflamed sinus mucosa, suggesting that sulfur compounds contribute to the pathogenesis of CRS. Level of Evidence: N/A.", "classifications": [ { "id": "JPMJCR2024", "label": "JPMJCR2024", "researcher": "Motohiro Nishida", "type": "grant" }, { "id": "Akaike", "label": "Group Akaike", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Group Nishida", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Jun", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Tomotaka", "last_name": "Hemmi", "name": null }, { "creator_type": "author", "first_name": "Tomoaki", "last_name": "Ida", "name": null }, { "creator_type": "author", "first_name": "Seiryo", "last_name": "Ogata", "name": null }, { "creator_type": "author", "first_name": "Jun", "last_name": "Yoshitake", "name": null }, { "creator_type": "author", "first_name": "Tetsuro", "last_name": "Matsunaga", "name": null }, { "creator_type": "author", "first_name": "Tomoyasu", "last_name": "Ishida", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Numano", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Kusano", "name": null }, { "creator_type": "author", "first_name": "Ryoukichi", "last_name": "Ikeda", "name": null }, { "creator_type": "author", "first_name": "Kazuhiro", "last_name": "Nomura", "name": null }, { "creator_type": "author", "first_name": "Mitsuru", "last_name": "Sugawara", "name": null }, { "creator_type": "author", "first_name": "Nobuo", "last_name": "Ohta", "name": null }, { "creator_type": "author", "first_name": "Takaaki", "last_name": "Akaike", "name": null }, { "creator_type": "author", "first_name": "Yukio", "last_name": "Katori", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/lio2.1261" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "39071205" } }, "mesh": [], "publication": { "conference_name": null, "date": "2024 Aug", "date_precision": "unknown", "issue": "4", "normalized_date": null, "pages": "", "proceedings_title": null, "publisher": "", "title": "Laryngoscope Investigative Otolaryngology", "volume": "9", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Supersulfide formation in the sinus mucosa of chronic rhinosinusitis.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Although hyponatremia and salt wasting are common in patients with HIV/AIDS, the understanding of their contributing factors is limited. HIV viral protein R (Vpr) contributes to HIV-associated nephropathy. To investigate the effects of Vpr on the distal tubules and on the expression level of the Slc12a3 gene, encoding the sodium-chloride cotransporter (which is responsible for sodium reabsorption in distal nephron segments), single-nucleus RNA sequencing was performed on kidney cortices from three wild-type (WT) and three Vpr transgenic (Vpr Tg) mice. The percentage of distal convoluted tubule (DCT) cells was significantly lower in Vpr Tg mice compared with WT mice (P < 0.05); in Vpr Tg mice, Slc12a3 expression was not significantly different in DCT cells. The Pvalb(+) DCT1 subcluster had fewer cells in Vpr Tg mice compared with those in WT mice (P < 0.01). Immunohistochemistry revealed fewer Slc12a3(+)Pvalb(+) DCT1 segments in Vpr Tg mice. Differential gene expression analysis between Vpr Tg and WT samples in the DCT cluster showed down-regulation of the Ier3 gene, which is an inhibitor of apoptosis. The in vitro knockdown of Ier3 by siRNA transfection induced apoptosis in mouse DCT cells. These observations suggest that the salt-wasting effect of Vpr in Vpr Tg mice is likely mediated by Ier3 down-regulation in DCT1 cells and loss of Slc12a3(+)Pvalb(+) DCT1 segments.", "classifications": [ { "id": "Okamoto", "label": "Group Okamoto", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Khun Zaw", "last_name": "Latt", "name": null }, { "creator_type": "author", "first_name": "Teruhiko", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Shashi", "last_name": "Shrivastav", "name": null }, { "creator_type": "author", "first_name": "Amin", "last_name": "Abedini", "name": null }, { "creator_type": "author", "first_name": "Jeff M.", "last_name": "Reece", "name": null }, { "creator_type": "author", "first_name": "Zeguo", "last_name": "Sun", "name": null }, { "creator_type": "author", "first_name": "Hewang", "last_name": "Lee", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Okamoto", "name": null }, { "creator_type": "author", "first_name": "Pradeep", "last_name": "Dagur", "name": null }, { "creator_type": "author", "first_name": "Yu", "last_name": "Ishimoto", "name": null }, { "creator_type": "author", "first_name": "Jurgen", "last_name": "Heymann", "name": null }, { "creator_type": "author", "first_name": "Yongmei", "last_name": "Zhao", "name": null }, { "creator_type": "author", "first_name": "Joon-Yong", "last_name": "Chung", "name": null }, { "creator_type": "author", "first_name": "Stephen", "last_name": "Hewitt", "name": null }, { "creator_type": "author", "first_name": "Pedro A.", "last_name": "Jose", "name": null }, { "creator_type": "author", "first_name": "Kyung", "last_name": "Lee", "name": null }, { "creator_type": "author", "first_name": "John Cijiang", "last_name": "He", "name": null }, { "creator_type": "author", "first_name": "Cheryl A.", "last_name": "Winkler", "name": null }, { "creator_type": "author", "first_name": "Mark A.", "last_name": "Knepper", "name": null }, { "creator_type": "author", "first_name": "Tomoshige", "last_name": "Kino", "name": null }, { "creator_type": "author", "first_name": "Avi Z.", "last_name": "Rosenberg", "name": null }, { "creator_type": "author", "first_name": "Katalin", "last_name": "Susztak", "name": null }, { "creator_type": "author", "first_name": "Jeffrey B.", "last_name": "Kopp", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.ajpath.2024.06.006" }, "pmcid": { "normalized": "PMC11536472" }, "pmid": { "normalized": "39032602" } }, "mesh": [ { "descriptor": "AIDS-Associated Nephropathy", "descriptor_ui": "D016263", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Kidney Tubules, Distal", "descriptor_ui": "D007686", "major_topic": true }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Transgenic", "descriptor_ui": "D008822", "major_topic": true }, { "descriptor": "Sequence Analysis, RNA", "descriptor_ui": "D017423", "major_topic": true }, { "descriptor": "Solute Carrier Family 12, Member 3", "descriptor_ui": "D064486", "major_topic": false }, { "descriptor": "vpr Gene Products, Human Immunodeficiency Virus", "descriptor_ui": "D054325", "major_topic": false } ], "publication": { "conference_name": null, "date": "2024 Oct", "date_precision": "unknown", "issue": "10", "normalized_date": null, "pages": "1844-1856", "proceedings_title": null, "publisher": "", "title": "The American journal of pathology", "volume": "194", "year": 2024 }, "ssbd": { "database": [], "repository": [] }, "title": "Single-Nucleus RNA Sequencing Reveals Loss of Distal Convoluted Tubule 1 Renal Tubules in HIV Viral Protein R Transgenic Mice.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: Haploidentical peripheral blood stem cell transplantation (haplo-PBSCT) with post-transplant cyclophosphamide (PTCy) is an important therapeutic option for patients lacking an HLA-matched donor. However, the significance of CD34(+) cell dose in grafts has not been fully elucidated. OBJECTIVE: We aimed to explore the impact of CD34(+) cell dose on outcomes after haplo-PBSCT with PTCy. STUDY DESIGN: We retrospectively investigated 111 consecutive patients who underwent haplo-PBSCT with PTCy or HLA-matched PBSCT from related donors. RESULTS: There were no statistically significant differences in 3-year overall survival (p = 0.559) or progression-free survival (p = 0.974) between haplo-PBSCT and matched PBSCT. Delayed neutrophil engraftment and a lower incidence of graft-versus-host disease were observed in haplo-PBSCT. The median dose of CD34(+) cells was 4.9 x 10(6) /kg in 57 haplo-PBSCT and 4.5 x 10(6) /kg in 54 matched PBSCTs. Importantly, patients who underwent haplo-PBSCT with the administration of CD34(+) cell at a dose of >/=4.0 x 10(6) /kg significantly had improved OS (p = 0.015) and decreased incidence of disease relapse (p = 0.001) without increasing incidence of GVHD. CONCLUSION: Our data suggest that a higher dose of CD34(+) cells in haplo-PBSCT with PTCy positively impacts the outcomes without an increase of GVHD.", "classifications": [ { "id": "Nishikii", "label": "Group Nishikii", "parent": "Shintaku", "type": "group" }, { "id": "Shintaku", "label": "Team Shintaku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yumiko", "last_name": "Maruyama", "name": null }, { "creator_type": "author", "first_name": "Hidekazu", "last_name": "Nishikii", "name": null }, { "creator_type": "author", "first_name": "Naoki", "last_name": "Kurita", "name": null }, { "creator_type": "author", "first_name": "Tatsuhiro", "last_name": "Sakamoto", "name": null }, { "creator_type": "author", "first_name": "Keiichiro", "last_name": "Hattori", "name": null }, { "creator_type": "author", "first_name": "Yasuhito", "last_name": "Suehara", "name": null }, { "creator_type": "author", "first_name": "Yasuhisa", "last_name": "Yokoyama", "name": null }, { "creator_type": "author", "first_name": "Takayasu", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Naoshi", "last_name": "Obara", "name": null }, { "creator_type": "author", "first_name": "Mamiko", "last_name": "Sakata-Yanagimoto", "name": null }, { "creator_type": "author", "first_name": "Shigeru", "last_name": "Chiba", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.bcmd.2023.102820" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "38199143" } }, "mesh": [ { "descriptor": "Cyclophosphamide", "descriptor_ui": "D003520", "major_topic": false }, { "descriptor": "Graft vs Host Disease", "descriptor_ui": "D006086", "major_topic": true }, { "descriptor": "Hematopoietic Stem Cell Transplantation", "descriptor_ui": "D018380", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Japan", "descriptor_ui": "D007564", "major_topic": false }, { "descriptor": "Peripheral Blood Stem Cell Transplantation", "descriptor_ui": "D036102", "major_topic": true }, { "descriptor": "Retrospective Studies", "descriptor_ui": "D012189", "major_topic": false }, { "descriptor": "Transplantation Conditioning", "descriptor_ui": "D019172", "major_topic": false } ], "publication": { "conference_name": null, "date": "2023 Dec 30", "date_precision": "day", "issue": "", "normalized_date": "2023-12-30", "pages": "102820", "proceedings_title": null, "publisher": "", "title": "Blood cells, molecules & diseases", "volume": "105", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Impact of CD34 positive cell dose in donor graft on the outcomes after haploidentical peripheral blood stem cell transplantation with post-transplant cyclophosphamide - A retrospective single-center study with a Japanese cohort.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Single-cell RNA-seq analysis coupled with CRISPR-based perturbation has enabled the inference of gene regulatory networks with causal relationships. However, a snapshot of single-cell CRISPR data may not lead to an accurate inference, since a gene knockout can influence multi-layered downstream over time. Here, we developed RENGE, a computational method that infers gene regulatory networks using a time-series single-cell CRISPR dataset. RENGE models the propagation process of the effects elicited by a gene knockout on its regulatory network. It can distinguish between direct and indirect regulations, which allows for the inference of regulations by genes that are not knocked out. RENGE therefore outperforms current methods in the accuracy of inferring gene regulatory networks. When used on a dataset we derived from human-induced pluripotent stem cells, RENGE yielded a network consistent with multiple databases and literature. Accurate inference of gene regulatory networks by RENGE would enable the identification of key factors for various biological systems.", "classifications": [ { "id": "JPMJCR1922", "label": "JPMJCR1922", "researcher": "Mototsugu Eiraku", "type": "grant" }, { "id": "Eiraku", "label": "Group Eiraku", "parent": "Eiraku", "type": "group" }, { "id": "Mochizuki", "label": "Group Mochizuki", "parent": "Eiraku", "type": "group" }, { "id": "Yusa", "label": "Group Yusa", "parent": "Eiraku", "type": "group" }, { "id": "Eiraku", "label": "Team Eiraku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Masato", "last_name": "Ishikawa", "name": null }, { "creator_type": "author", "first_name": "Seiichi", "last_name": "Sugino", "name": null }, { "creator_type": "author", "first_name": "Yoshie", "last_name": "Masuda", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Tarumoto", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Seto", "name": null }, { "creator_type": "author", "first_name": "Nobuko", "last_name": "Taniyama", "name": null }, { "creator_type": "author", "first_name": "Fumi", "last_name": "Wagai", "name": null }, { "creator_type": "author", "first_name": "Yuhei", "last_name": "Yamauchi", "name": null }, { "creator_type": "author", "first_name": "Yasuhiro", "last_name": "Kojima", "name": null }, { "creator_type": "author", "first_name": "Hisanori", "last_name": "Kiryu", "name": null }, { "creator_type": "author", "first_name": "Kosuke", "last_name": "Yusa", "name": null }, { "creator_type": "author", "first_name": "Mototsugu", "last_name": "Eiraku", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Mochizuki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s42003-023-05594-4" }, "pmcid": { "normalized": "PMC10754834" }, "pmid": { "normalized": "38155269" } }, "mesh": [ { "descriptor": "Gene Knockout Techniques", "descriptor_ui": "D055786", "major_topic": false }, { "descriptor": "Gene Regulatory Networks", "descriptor_ui": "D053263", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Single-Cell Gene Expression Analysis", "descriptor_ui": "D000092386", "major_topic": true }, { "descriptor": "Time Factors", "descriptor_ui": "D013997", "major_topic": false } ], "publication": { "conference_name": null, "date": "2023 Dec 28", "date_precision": "day", "issue": "1", "normalized_date": "2023-12-28", "pages": "1290", "proceedings_title": null, "publisher": "", "title": "Communications biology", "volume": "6", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "RENGE infers gene regulatory networks using time-series single-cell RNA-seq data with CRISPR perturbations.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Human hematopoietic stem cells (HSCs) are widely used as a cellular source for hematopoietic stem cell transplantation (HSCT) in the clinical treatment of hematological malignancies. After transplantation therapy, delays in hematopoietic recovery due to insufficient donor-derived HSCs can lead to increased risks of life-threatening infections and bleeding. Our previous studies developed an efficient ex vivo expansion culture medium (3a medium) for umbilical cord blood-derived HSCs (CBSCs), offering a potential solution to this problem. Nevertheless, the broader applicability of our culture method to alternative cell sources, and, of greater significance, its efficacy in eliminating potentially disease-associated contaminated tumor cells, especially in autologous transplantation, raises critical clinical questions. In this study, we modified the 3a medium by incorporating UM729 to replace UM171, added Flt3 ligand, and adjusted the concentrations of butyzamide, 740Y-P, polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer (PCL-PVAc-PEG, Soluplus((R)ฎ)) to create the modified 3a medium. This sophistication allowed efficient expansion of not only CBSCs but also peripheral blood mobilized HSCs (PBSCs). Additionally, we successfully removed contaminated myeloma cells by adding bortezomib and TNF-related apoptosis inducing ligand (TRAIL) at appropriate concentrations, while maintaining HSCs through the addition of lenalidomide. Our research findings present the potential for widespread clinical application of the modified 3a medium and suggest a safe ex vivo culture technique for expanding human HSCs within peripheral blood derived donor grafts used for autologous HSCT.", "classifications": [ { "id": "Nishikii", "label": "Group Nishikii", "parent": "Shintaku", "type": "group" }, { "id": "Shintaku", "label": "Team Shintaku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Kantaro", "last_name": "Ishitsuka", "name": null }, { "creator_type": "author", "first_name": "Hidekazu", "last_name": "Nishikii", "name": null }, { "creator_type": "author", "first_name": "Takaharu", "last_name": "Kimura", "name": null }, { "creator_type": "author", "first_name": "Ayano", "last_name": "Sugiyama-Finnis", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Yamazaki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.exphem.2023.104138" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "38151170" } }, "mesh": [ { "descriptor": "Hematopoietic Stem Cells", "descriptor_ui": "D006412", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Ligands", "descriptor_ui": "D008024", "major_topic": false }, { "descriptor": "Multiple Myeloma", "descriptor_ui": "D009101", "major_topic": true }, { "descriptor": "Peptide Fragments", "descriptor_ui": "D010446", "major_topic": true }, { "descriptor": "Peripheral Blood Stem Cells", "descriptor_ui": "D000072916", "major_topic": true }, { "descriptor": "Polyethylene Glycols", "descriptor_ui": "D011092", "major_topic": true }, { "descriptor": "Polyvinyls", "descriptor_ui": "D011145", "major_topic": true }, { "descriptor": "Receptors, Platelet-Derived Growth Factor", "descriptor_ui": "D017479", "major_topic": true } ], "publication": { "conference_name": null, "date": "2023 Dec 25", "date_precision": "day", "issue": "", "normalized_date": "2023-12-25", "pages": "104138", "proceedings_title": null, "publisher": "", "title": "Experimental hematology", "volume": "", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Purging myeloma cell contaminants and simultaneous expansion of peripheral blood mobilised stem cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Pancreatic islet transplantation presents a promising therapy for individuals suffering from type 1 diabetes. To maintain the function of transplanted islets in vivo, it is imperative to induce angiogenesis. However, the mechanisms underlying angiogenesis triggered by islets remain unclear. In this study, we introduced a microphysiological system to study the angiogenic capacity and dynamics of individual islets. The system, which features an open-top structure, uniquely facilitates the inoculation of islets and the longitudinal observation of vascular formation in in vivo like microenvironment with islet-endothelial cell communication. By leveraging our system, we discovered notable islet-islet heterogeneity in the angiogenic capacity. Transcriptomic analysis of the vascularized islets revealed that islets with high angiogenic capacity exhibited upregulation of genes related to insulin secretion and downregulation of genes related to angiogenesis and fibroblasts. In conclusion, our microfluidic approach is effective in characterizing the vascular formation of individual islets and holds great promise for elucidating the angiogenic mechanisms that enhance islet transplantation therapy.", "classifications": [ { "id": "Shintaku", "label": "Group Shintaku", "parent": "Shintaku", "type": "group" }, { "id": "Shintaku", "label": "Team Shintaku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yuji", "last_name": "Nashimoto", "name": null }, { "creator_type": "author", "first_name": "An", "last_name": "Konno", "name": null }, { "creator_type": "author", "first_name": "Takuto", "last_name": "Imaizumi", "name": null }, { "creator_type": "author", "first_name": "Kaori", "last_name": "Nishikawa", "name": null }, { "creator_type": "author", "first_name": "Kosuke", "last_name": "Ino", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Hori", "name": null }, { "creator_type": "author", "first_name": "Hirokazu", "last_name": "Kaji", "name": null }, { "creator_type": "author", "first_name": "Hirofumi", "last_name": "Shintaku", "name": null }, { "creator_type": "author", "first_name": "Masafumi", "last_name": "Goto", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Shiku", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/bit.28631" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "38131167" } }, "mesh": [ { "descriptor": "Diabetes Mellitus, Type 1", "descriptor_ui": "D003922", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Insulin Secretion", "descriptor_ui": "D000078790", "major_topic": false }, { "descriptor": "Islets of Langerhans", "descriptor_ui": "D007515", "major_topic": true }, { "descriptor": "Islets of Langerhans Transplantation", "descriptor_ui": "D016381", "major_topic": true }, { "descriptor": "Microfluidics", "descriptor_ui": "D044085", "major_topic": false } ], "publication": { "conference_name": null, "date": "2023 Dec 22", "date_precision": "day", "issue": "", "normalized_date": "2023-12-22", "pages": "", "proceedings_title": null, "publisher": "", "title": "Biotechnology and bioengineering", "volume": "", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Microfluidic vascular formation model for assessing angiogenic capacities of single islets.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Recent regenerative studies using human pluripotent stem cells (hPSCs) have developed multiple kidney-lineage cells and organoids. However, to further form functional segments of the kidney, interactions of epithelial and interstitial cells are required. Here we describe a selective differentiation of renal interstitial progenitor-like cells (IPLCs) from human induced pluripotent stem cells (hiPSCs) by modifying our previous induction method for nephron progenitor cells (NPCs) and analyzing mouse embryonic interstitial progenitor cell (IPC) development. Our IPLCs combined with hiPSC-derived NPCs and nephric duct cells form nephrogenic niche- and mesangium-like structures in vitro. Furthermore, we successfully induce hiPSC-derived IPLCs to differentiate into mesangial and erythropoietin-producing cell lineages in vitro by screening differentiation-inducing factors and confirm that p38 MAPK, hypoxia, and VEGF signaling pathways are involved in the differentiation of mesangial-lineage cells. These findings indicate that our IPC-lineage induction method contributes to kidney regeneration and developmental research.", "classifications": [ { "id": "Yamamoto", "label": "Group Yamamoto", "parent": "Toyoshima", "type": "group" }, { "id": "Toyoshima", "label": "Team Toyoshima", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Hiraku", "last_name": "Tsujimoto", "name": null }, { "creator_type": "author", "first_name": "Azusa", "last_name": "Hoshina", "name": null }, { "creator_type": "author", "first_name": "Shin-Ichi", "last_name": "Mae", "name": null }, { "creator_type": "author", "first_name": "Toshikazu", "last_name": "Araoka", "name": null }, { "creator_type": "author", "first_name": "Wang", "last_name": "Changting", "name": null }, { "creator_type": "author", "first_name": "Yoshihiro", "last_name": "Ijiri", "name": null }, { "creator_type": "author", "first_name": "May", "last_name": "Nakajima-Koyama", "name": null }, { "creator_type": "author", "first_name": "Satoko", "last_name": "Sakurai", "name": null }, { "creator_type": "author", "first_name": "Kazusa", "last_name": "Okita", "name": null }, { "creator_type": "author", "first_name": "Ken", "last_name": "Mizuta", "name": null }, { "creator_type": "author", "first_name": "Akira", "last_name": "Niwa", "name": null }, { "creator_type": "author", "first_name": "Megumu K.", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Mitinori", "last_name": "Saitou", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Cecilia", "last_name": "Graneli", "name": null }, { "creator_type": "author", "first_name": "Kevin J.", "last_name": "Woollard", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Osafune", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.celrep.2023.113602" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "38237600" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Lineage", "descriptor_ui": "D019070", "major_topic": false }, { "descriptor": "Erythropoietin", "descriptor_ui": "D004921", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Induced Pluripotent Stem Cells", "descriptor_ui": "D057026", "major_topic": true }, { "descriptor": "Kidney", "descriptor_ui": "D007668", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Regeneration", "descriptor_ui": "D012038", "major_topic": false } ], "publication": { "conference_name": null, "date": "2023 Dec 22", "date_precision": "day", "issue": "", "normalized_date": "2023-12-22", "pages": "113602", "proceedings_title": null, "publisher": "", "title": "Cell reports", "volume": "", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Selective induction of human renal interstitial progenitor-like cell lineages from iPSCs reveals development of mesangial and EPO-producing cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Organoids, which can reproduce the complex tissue structures found in embryos, are revolutionizing basic research and regenerative medicine. In order to use organoids for research and medicine, it is necessary to assess the composition and arrangement of cell types within the organoid, i.e., spatial gene expression. However, current methods are invasive and require gene editing and immunostaining. In this study, we developed a non-invasive estimation method of spatial gene expression patterns using machine learning. A deep learning model with an encoder-decoder architecture was trained on paired datasets of phase-contrast and fluorescence images, and was applied to a retinal organoid derived from mouse embryonic stem cells, focusing on the master gene Rax (also called Rx), crucial for eye field development. This method successfully estimated spatially plausible fluorescent patterns with appropriate intensities, enabling the non-invasive, quantitative estimation of spatial gene expression patterns within each tissue. Thus, this method could lead to new avenues for evaluating spatial gene expression patterns across a wide range of biology and medicine fields.", "classifications": [ { "id": "JPMJCR1921", "label": "JPMJCR1921", "researcher": "Itaru Imayoshi", "type": "grant" }, { "id": "Imayoshi", "label": "Group Imayoshi", "parent": "Imayoshi", "type": "group" }, { "id": "Okuda", "label": "Group Okuda", "parent": "Imayoshi", "type": "group" }, { "id": "Imayoshi", "label": "Team Imayoshi", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yuki", "last_name": "Fujimura", "name": null }, { "creator_type": "author", "first_name": "Itsuki", "last_name": "Sakai", "name": null }, { "creator_type": "author", "first_name": "Itsuki", "last_name": "Shioka", "name": null }, { "creator_type": "author", "first_name": "Nozomu", "last_name": "Takata", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Funatomi", "name": null }, { "creator_type": "author", "first_name": "Satoru", "last_name": "Okuda", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41598-023-49758-y" }, "pmcid": { "normalized": "PMC10733327" }, "pmid": { "normalized": "38123631" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Gene Expression", "descriptor_ui": "D015870", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Organoids", "descriptor_ui": "D009940", "major_topic": false }, { "descriptor": "Pluripotent Stem Cells", "descriptor_ui": "D039904", "major_topic": true }, { "descriptor": "Regenerative Medicine", "descriptor_ui": "D044968", "major_topic": false }, { "descriptor": "Retina", "descriptor_ui": "D012160", "major_topic": true } ], "publication": { "conference_name": null, "date": "2023 Dec 20", "date_precision": "day", "issue": "1", "normalized_date": "2023-12-20", "pages": "22781", "proceedings_title": null, "publisher": "", "title": "Scientific reports", "volume": "13", "year": 2023 }, "ssbd": { "database": [], "repository": [ "ssbd-repos-000382" ] }, "title": "Machine learning-based estimation of spatial gene expression pattern during ESC-derived retinal organoid development.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "A comprehensive and quantitative evaluation of multiple intracellular structures or proteins is a promising approach to provide a deeper understanding of and new insights into cellular polarity. In this study, we developed an image analysis pipeline to obtain intensity profiles of fluorescent probes along the apical-basal axis in elongating Arabidopsis thaliana zygotes based on two-photon live-cell imaging data. This technique showed the intracellular distribution of actin filaments, mitochondria, microtubules, and vacuolar membranes along the apical-basal axis in elongating zygotes from the onset of cell elongation to just before asymmetric cell division. Hierarchical cluster analysis of the quantitative data on intracellular distribution revealed that the zygote may be compartmentalized into two parts, with a boundary located 43.6% from the cell tip, immediately after fertilization. To explore the biological significance of this compartmentalization, we examined the positions of the asymmetric cell divisions from the dataset used in this distribution analysis. We found that the cell division plane was reproducibly inserted 20.5% from the cell tip. This position corresponded well with the midpoint of the compartmentalized apical region, suggesting a potential relationship between the zygote compartmentalization, which begins with cell elongation, and the position of the asymmetric cell division.", "classifications": [ { "id": "JPMJCR2121", "label": "JPMJCR2121", "researcher": "Minako Ueda", "type": "grant" }, { "id": "Higaki", "label": "Group Higaki", "parent": "Ueda", "type": "group" }, { "id": "Ueda", "label": "Group Ueda", "parent": "Ueda", "type": "group" }, { "id": "Ueda", "label": "Team Ueda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yukiko", "last_name": "Hiromoto", "name": null }, { "creator_type": "author", "first_name": "Naoki", "last_name": "Minamino", "name": null }, { "creator_type": "author", "first_name": "Suzuka", "last_name": "Kikuchi", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Kimata", "name": null }, { "creator_type": "author", "first_name": "Hikari", "last_name": "Matsumoto", "name": null }, { "creator_type": "author", "first_name": "Sakumi", "last_name": "Nakagawa", "name": null }, { "creator_type": "author", "first_name": "Minako", "last_name": "Ueda", "name": null }, { "creator_type": "author", "first_name": "Takumi", "last_name": "Higaki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41598-023-50020-8" }, "pmcid": { "normalized": "PMC10739889" }, "pmid": { "normalized": "38129559" } }, "mesh": [ { "descriptor": "Arabidopsis", "descriptor_ui": "D017360", "major_topic": true }, { "descriptor": "Asymmetric Cell Division", "descriptor_ui": "D060049", "major_topic": false }, { "descriptor": "Cell Cycle", "descriptor_ui": "D002453", "major_topic": false }, { "descriptor": "Cell Division", "descriptor_ui": "D002455", "major_topic": false }, { "descriptor": "Cell Polarity", "descriptor_ui": "D016764", "major_topic": false }, { "descriptor": "Zygote", "descriptor_ui": "D015053", "major_topic": false } ], "publication": { "conference_name": null, "date": "2023 Dec 18", "date_precision": "day", "issue": "1", "normalized_date": "2023-12-18", "pages": "22879", "proceedings_title": null, "publisher": "", "title": "Scientific reports", "volume": "13", "year": 2023 }, "ssbd": { "database": [ "ssbd-database-000383" ], "repository": [ "ssbd-repos-000383" ] }, "title": "Comprehensive and quantitative analysis of intracellular structure polarization at the apical-basal axis in elongating Arabidopsis zygotes.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The mechanism underlying the development of tumors, particularly at early stages, still remains mostly elusive. Here, we report whole-genome long and short read sequencing analysis of 76 lung cancers, focusing on very early-stage lung adenocarcinomas such as adenocarcinoma in situ (AIS) and minimally invasive adenocarcinoma. The obtained data is further integrated with bulk and spatial transcriptomic data and epigenomic data. These analyses reveal key events in lung carcinogenesis. Minimal somatic mutations in pivotal driver mutations and essential proliferative factors are the only detectable somatic mutations in the very early-stage of AIS. These initial events are followed by copy number changes and global DNA hypomethylation. Particularly, drastic changes are initiated at the later AIS stage, i.e., in Noguchi type B tumors, wherein cancer cells are exposed to the surrounding microenvironment. This study sheds light on the pathogenesis of lung adenocarcinoma from integrated pathological and molecular viewpoints.", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yasuhiko", "last_name": "Haga", "name": null }, { "creator_type": "author", "first_name": "Yoshitaka", "last_name": "Sakamoto", "name": null }, { "creator_type": "author", "first_name": "Keiko", "last_name": "Kajiya", "name": null }, { "creator_type": "author", "first_name": "Hitomi", "last_name": "Kawai", "name": null }, { "creator_type": "author", "first_name": "Miho", "last_name": "Oka", "name": null }, { "creator_type": "author", "first_name": "Noriko", "last_name": "Motoi", "name": null }, { "creator_type": "author", "first_name": "Masayuki", "last_name": "Shirasawa", "name": null }, { "creator_type": "author", "first_name": "Masaya", "last_name": "Yotsukura", "name": null }, { "creator_type": "author", "first_name": "Shun-Ichi", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Miyuki", "last_name": "Arai", "name": null }, { "creator_type": "author", "first_name": "Junko", "last_name": "Zenkoh", "name": null }, { "creator_type": "author", "first_name": "Kouya", "last_name": "Shiraishi", "name": null }, { "creator_type": "author", "first_name": "Masahide", "last_name": "Seki", "name": null }, { "creator_type": "author", "first_name": "Akinori", "last_name": "Kanai", "name": null }, { "creator_type": "author", "first_name": "Yuichi", "last_name": "Shiraishi", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Matsubara", "name": null }, { "creator_type": "author", "first_name": "Yutaka", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Masayuki", "last_name": "Noguchi", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Kohno", "name": null }, { "creator_type": "author", "first_name": "Ayako", "last_name": "Suzuki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41467-023-43732-y" }, "pmcid": { "normalized": "PMC10724178" }, "pmid": { "normalized": "38102134" } }, "mesh": [ { "descriptor": "Adenocarcinoma", "descriptor_ui": "D000230", "major_topic": true }, { "descriptor": "Adenocarcinoma in Situ", "descriptor_ui": "D065311", "major_topic": true }, { "descriptor": "Adenocarcinoma of Lung", "descriptor_ui": "D000077192", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Lung", "descriptor_ui": "D008168", "major_topic": false }, { "descriptor": "Lung Neoplasms", "descriptor_ui": "D008175", "major_topic": true }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": false }, { "descriptor": "Tumor Microenvironment", "descriptor_ui": "D059016", "major_topic": false } ], "publication": { "conference_name": null, "date": "2023 Dec 15", "date_precision": "day", "issue": "1", "normalized_date": "2023-12-15", "pages": "8375", "proceedings_title": null, "publisher": "", "title": "Nature communications", "volume": "14", "year": 2023 }, "ssbd": { "database": [], "repository": [ "ssbd-repos-000457" ] }, "title": "Whole-genome sequencing reveals the molecular implications of the stepwise progression of lung adenocarcinoma.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Skeletal muscle atrophy and the inhibition of muscle regeneration are known to occur as a natural consequence of aging, yet the underlying mechanisms that lead to these processes in atrophic myofibers remain largely unclear. Our research has revealed that the maintenance of proper mitochondrial-associated endoplasmic reticulum membranes (MAM) is vital for preventing skeletal muscle atrophy in microgravity environments. We discovered that the deletion of the mitochondrial fusion protein Mitofusin2 (MFN2), which serves as a tether for MAM, in human induced pluripotent stem (iPS) cells or the reduction of MAM in differentiated myotubes caused by microgravity interfered with myogenic differentiation process and an increased susceptibility to muscle atrophy, as well as the activation of the Notch signaling pathway. The atrophic phenotype of differentiated myotubes in microgravity and the regenerative capacity of Mfn2-deficient muscle stem cells in dystrophic mice were both ameliorated by treatment with the gamma-secretase inhibitor DAPT. Our findings demonstrate how the orchestration of mitochondrial morphology in differentiated myotubes and regenerating muscle stem cells plays a crucial role in regulating Notch signaling through the interaction of MAM.", "classifications": [ { "id": "Yamamoto", "label": "Group Yamamoto", "parent": "Toyoshima", "type": "group" }, { "id": "Toyoshima", "label": "Team Toyoshima", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yurika", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Mari", "last_name": "Yamagata", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Katsuya", "last_name": "Hirasaka", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Nikawa", "name": null }, { "creator_type": "author", "first_name": "Takahiko", "last_name": "Sato", "name": null } ], "identifiers": { "doi": { "normalized": "10.7554/elife.89381" }, "pmcid": { "normalized": "PMC10723794" }, "pmid": { "normalized": "38099641" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mitochondria", "descriptor_ui": "D008928", "major_topic": false }, { "descriptor": "Muscle Fibers, Skeletal", "descriptor_ui": "D018485", "major_topic": false }, { "descriptor": "Muscle, Skeletal", "descriptor_ui": "D018482", "major_topic": false }, { "descriptor": "Muscular Atrophy", "descriptor_ui": "D009133", "major_topic": true }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Weightlessness", "descriptor_ui": "D014893", "major_topic": true } ], "publication": { "conference_name": null, "date": "2023 Dec 15", "date_precision": "day", "issue": "", "normalized_date": "2023-12-15", "pages": "", "proceedings_title": null, "publisher": "", "title": "eLife", "volume": "12", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "The reciprocal regulation between mitochondrial-associated membranes and Notch signaling in skeletal muscle atrophy.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Nicotinamide phosphoribosyltransferase (NAMPT) plays a major role in NAD biosynthesis in many cancers and is an attractive potential cancer target. However, factors dictating therapeutic efficacy of NAMPT inhibitors (NAMPTi) are unclear. We report that neuroendocrine phenotypes predict lung and prostate carcinoma vulnerability to NAMPTi, and that NAMPTi therapy against those cancers is enhanced by dietary modification. Neuroendocrine differentiation of tumor cells is associated with down-regulation of genes relevant to quinolinate phosphoribosyltransferase-dependent de novo NAD synthesis, promoting NAMPTi susceptibility in vitro. We also report that circulating nicotinic acid riboside (NAR), a non-canonical niacin absent in culture media, antagonizes NAMPTi efficacy as it fuels NAMPT-independent but nicotinamide riboside kinase 1-dependent NAD synthesis in tumors. In mouse transplantation models, depleting blood NAR by nutritional or genetic manipulations is synthetic lethal to tumors when combined with NAMPTi. Our findings provide a rationale for simultaneous targeting of NAR metabolism and NAMPT therapeutically in neuroendocrine carcinoma.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Miyuki", "last_name": "Nomura", "name": null }, { "creator_type": "author", "first_name": "Mai", "last_name": "Ohuchi", "name": null }, { "creator_type": "author", "first_name": "Yoshimi", "last_name": "Sakamoto", "name": null }, { "creator_type": "author", "first_name": "Kei", "last_name": "Kudo", "name": null }, { "creator_type": "author", "first_name": "Keisuke", "last_name": "Yaku", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Sugiura", "name": null }, { "creator_type": "author", "first_name": "Mami", "last_name": "Morita", "name": null }, { "creator_type": "author", "first_name": "Kayoko", "last_name": "Hayashi", "name": null }, { "creator_type": "author", "first_name": "Shuko", "last_name": "Miyahara", "name": null }, { "creator_type": "author", "first_name": "Taku", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Yoji", "last_name": "Yamashita", "name": null }, { "creator_type": "author", "first_name": "Shigemi", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Naohiko", "last_name": "Kikuchi", "name": null }, { "creator_type": "author", "first_name": "Ikuro", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Rintaro", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Nobuo", "last_name": "Yaegashi", "name": null }, { "creator_type": "author", "first_name": "Tatsuro", "last_name": "Fukuhara", "name": null }, { "creator_type": "author", "first_name": "Hidekazu", "last_name": "Yamada", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Shima", "name": null }, { "creator_type": "author", "first_name": "Keiichi I.", "last_name": "Nakayama", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Hirao", "name": null }, { "creator_type": "author", "first_name": "Kenta", "last_name": "Kawasaki", "name": null }, { "creator_type": "author", "first_name": "Yoichi", "last_name": "Arai", "name": null }, { "creator_type": "author", "first_name": "Shusuke", "last_name": "Akamatsu", "name": null }, { "creator_type": "author", "first_name": "Sei-Ichi", "last_name": "Tanuma", "name": null }, { "creator_type": "author", "first_name": "Toshiro", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Nakagawa", "name": null }, { "creator_type": "author", "first_name": "Nobuhiro", "last_name": "Tanuma", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41467-023-43630-3" }, "pmcid": { "normalized": "PMC10719245" }, "pmid": { "normalized": "38092728" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Carcinoma, Neuroendocrine", "descriptor_ui": "D018278", "major_topic": true }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Cytokines", "descriptor_ui": "D016207", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "NAD", "descriptor_ui": "D009243", "major_topic": false }, { "descriptor": "Niacin", "descriptor_ui": "D009525", "major_topic": true }, { "descriptor": "Nicotinamide Phosphoribosyltransferase", "descriptor_ui": "D054409", "major_topic": false } ], "publication": { "conference_name": null, "date": "2023 Dec 13", "date_precision": "day", "issue": "1", "normalized_date": "2023-12-13", "pages": "8095", "proceedings_title": null, "publisher": "", "title": "Nature communications", "volume": "14", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Niacin restriction with NAMPT-inhibition is synthetic lethal to neuroendocrine carcinoma.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The exogenous administration of nitric oxide (NO) is considered a potential therapeutic treatment against a great variety of diseases due to its significant role in multiple physiological functions. Due to the gaseous nature, short lifetime and dose- and tissue-dependent activity of this molecule, the development of new administration procedures is required to control the NO delivery in terms of dosage, timing, and location. In this work, we propose a new molecular material based on robust metal-organic polyhedra (MOPs) for controlled NO release. We select dirhodium paddlewheel complex-based cuboctahedral MOPs (RhMOP), in which NO can chemically coordinate to the open-metal sites at the axial sites of dirhodium paddlewheel moieties. We further prepare amorphous coordination polymer particles (CPPs) by connecting RhMOP with bis(imidazole) linkers at the external axial sites. Both molecular MOPs and polymeric CPPs show relevant NO payloads and the release of NO can be triggered by two different stimuli: light and humidity. We show that imidazole ligands coordinating to the external axial sites of the paddlewheel moieties tune the light-triggered NO release property. We further demonstrate that the size and the extrinsic pores of CPPs are important for enhanced NO release.", "classifications": [ { "id": "Hijikata", "label": "Group Hijikata", "parent": "Tsuchiya", "type": "group" }, { "id": "Tsuchiya", "label": "Team Tsuchiya", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Francisco J.", "last_name": "Carmona", "name": null }, { "creator_type": "author", "first_name": "Thiago", "last_name": "Negrao Chuba", "name": null }, { "creator_type": "author", "first_name": "Eli", "last_name": "Sanchez-Gonzalez", "name": null }, { "creator_type": "author", "first_name": "Jenny", "last_name": "Pirillo", "name": null }, { "creator_type": "author", "first_name": "Yuh", "last_name": "Hijikata", "name": null }, { "creator_type": "author", "first_name": "Shuhei", "last_name": "Furukawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1039/d3tb02162a" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "38084014" } }, "mesh": [ { "descriptor": "Imidazoles", "descriptor_ui": "D007093", "major_topic": false }, { "descriptor": "Nitric Oxide", "descriptor_ui": "D009569", "major_topic": true }, { "descriptor": "Polymers", "descriptor_ui": "D011108", "major_topic": false }, { "descriptor": "Rhodium", "descriptor_ui": "D012238", "major_topic": true } ], "publication": { "conference_name": null, "date": "2023 Dec 12", "date_precision": "day", "issue": "", "normalized_date": "2023-12-12", "pages": "", "proceedings_title": null, "publisher": "", "title": "Journal of materials chemistry. B", "volume": "", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Dual photoresponsive & water-triggered nitric oxide releasing materials based on rhodium-based metal-organic polyhedra.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Hepatocellular carcinoma (HCC) has a high rate of recurrence and poor prognosis, even after curative surgery. Multikinase inhibitors have been applied for HCC patients, but their effect has been restricted. This study aims to clarify the clinical impact of SUV420H1/KMT5B, one of the methyltransferases for histone H4 at lysine 20, and elucidate the novel mechanisms of HCC progression. We retrospectively investigated SUV420H1 expression using HCC clinical tissue samples employing immunohistochemical analysis (n = 350). We then performed loss-of-function analysis of SUV420H1 with cell cycle analysis, migration assay, invasion assay and RNA sequence for Gene Ontology (GO) pathway analysis in vitro, and animal experiments with xenograft mice in vivo. The SUV420H1-high-score group (n = 154) had significantly poorer prognosis for both 5-year overall and 2-year/5-year disease-free survival than the SUV420H1-low-score group (n = 196) (p < 0.001 and p < 0.05, respectively). The SUV420H1-high-score group had pathologically larger tumor size, more tumors, poorer differentiation, and more positive vascular invasion than the SUV420H1-low-score group. Multivariate analysis demonstrated that SUV420H1 high score was the poorest independent factor for overall survival. SUV420H1 knockdown could suppress cell cycle from G1 to S phase and cell invasion. GO pathway analysis showed that SUV420H1 contributed to cell proliferation, cell invasion, and/or metastasis. Overexpression of SUV420H1 clinically contributed to poor prognosis in HCC, and the inhibition of SUV420H1 could repress tumor progression and invasion both in vitro and in vivo; thus, further analyses of SUV420H1 are necessary for the discovery of future molecularly targeted drugs.", "classifications": [ { "id": "Hamamoto", "label": "Group Hamamoto", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Hirotaka", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Hayami", "name": null }, { "creator_type": "author", "first_name": "Masaki", "last_name": "Ueno", "name": null }, { "creator_type": "author", "first_name": "Norihiko", "last_name": "Suzaki", "name": null }, { "creator_type": "author", "first_name": "Masashi", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Tomohiro", "last_name": "Yoshimura", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Miyamoto", "name": null }, { "creator_type": "author", "first_name": "Yoshinobu", "last_name": "Shigekawa", "name": null }, { "creator_type": "author", "first_name": "Ken-Ichi", "last_name": "Okada", "name": null }, { "creator_type": "author", "first_name": "Motoki", "last_name": "Miyazawa", "name": null }, { "creator_type": "author", "first_name": "Yuji", "last_name": "Kitahata", "name": null }, { "creator_type": "author", "first_name": "Shogo", "last_name": "Ehata", "name": null }, { "creator_type": "author", "first_name": "Ryuji", "last_name": "Hamamoto", "name": null }, { "creator_type": "author", "first_name": "Hiroki", "last_name": "Yamaue", "name": null }, { "creator_type": "author", "first_name": "Manabu", "last_name": "Kawai", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/cas.16038" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "38082550" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Carcinoma, Hepatocellular", "descriptor_ui": "D006528", "major_topic": true }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Cell Movement", "descriptor_ui": "D002465", "major_topic": false }, { "descriptor": "Cell Proliferation", "descriptor_ui": "D049109", "major_topic": false }, { "descriptor": "Gene Expression Regulation, Neoplastic", "descriptor_ui": "D015972", "major_topic": false }, { "descriptor": "Histone Methyltransferases", "descriptor_ui": "D000076983", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Liver Neoplasms", "descriptor_ui": "D008113", "major_topic": true }, { "descriptor": "Methyltransferases", "descriptor_ui": "D008780", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Prognosis", "descriptor_ui": "D011379", "major_topic": false }, { "descriptor": "Retrospective Studies", "descriptor_ui": "D012189", "major_topic": false } ], "publication": { "conference_name": null, "date": "2023 Dec 11", "date_precision": "day", "issue": "", "normalized_date": "2023-12-11", "pages": "", "proceedings_title": null, "publisher": "", "title": "Cancer science", "volume": "", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Histone methyltransferase SUV420H1/KMT5B contributes to poor prognosis in hepatocellular carcinoma.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Morphometric studies have revealed the existence of simple geometric relationships among various animal shapes. However, we have little knowledge of the mathematical principles behind the morphogenetic dynamics that form the organ/body shapes of different species. Here, we address this issue by focusing on limb morphogenesis in Gallus gallus domesticus (chicken) and Xenopus laevis (African clawed frog). To compare the deformation dynamics between tissues with different sizes/shapes as well as their developmental rates, we introduce a species-specific rescaled spatial coordinate and a common clock necessary for cross-species synchronization of developmental times. We find that tissue dynamics are well conserved across species under this spacetime coordinate system, at least from the early stages of development through the phase when basic digit patterning is established. For this developmental period, we also reveal that the tissue dynamics of both species are mapped with each other through a time-variant linear transformation in real physical space, from which hypotheses on a species-independent archetype of tissue dynamics and morphogenetic scaling are proposed.", "classifications": [ { "id": "JPMJCR2025", "label": "JPMJCR2025", "researcher": "Yoshihiro Morishita", "type": "grant" }, { "id": "Morishita", "label": "Group Morishita", "parent": "Morishita", "type": "group" }, { "id": "Morishita", "label": "Team Morishita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yoshihiro", "last_name": "Morishita", "name": null }, { "creator_type": "author", "first_name": "Sang-Woo", "last_name": "Lee", "name": null }, { "creator_type": "author", "first_name": "Takayuki", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Yokoyama", "name": null }, { "creator_type": "author", "first_name": "Yasuhiro", "last_name": "Kamei", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Tamura", "name": null }, { "creator_type": "author", "first_name": "Aiko", "last_name": "Kawasumi-Kita", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41467-023-43902-y" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "38081837" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Morphogenesis", "descriptor_ui": "D009024", "major_topic": false }, { "descriptor": "Organogenesis", "descriptor_ui": "D038081", "major_topic": true }, { "descriptor": "Xenopus laevis", "descriptor_ui": "D014982", "major_topic": false } ], "publication": { "conference_name": null, "date": "2023 Dec 11", "date_precision": "day", "issue": "1", "normalized_date": "2023-12-11", "pages": "8199", "proceedings_title": null, "publisher": "", "title": "Nature communications", "volume": "14", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "An archetype and scaling of developmental tissue dynamics across species.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Philadelphia chromosome (Ph)-like acute lymphoblastic leukemia (ALL) is a subset of ALL that demonstrated a high treatment failure rate. One of the hallmarks of Ph-like ALL is PDGFRB gene fusion, with fusion partner proteins often harboring dimerization domains and enhancing the kinase activity of PDGFRB. We determined a novel oncogenic PDGFRB fusion gene, NRIP1::PDGFRB, from a pediatric patient with ALL, encoding a protein with the carboxy-terminal kinase domain of PDGFRB, without the partner peptide. We confirmed the oncogenic potential of NRIP1::PDGFRB in vitro and the efficacy of all ABL1-specific inhibitor generations, including imatinib, dasatinib, nilotinib, and ponatinib, in suppressing this potential. PDGFRB activation mechanism may include juxtamembrane domain truncation in the predicted peptide. In conclusion, we determined a novel fusion gene pattern in Ph-like ALL.", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Bunpei", "last_name": "Miyazaki", "name": null }, { "creator_type": "author", "first_name": "Toshihide", "last_name": "Ueno", "name": null }, { "creator_type": "author", "first_name": "Masanaka", "last_name": "Sugiyama", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Kojima", "name": null }, { "creator_type": "author", "first_name": "Ayumu", "last_name": "Arakawa", "name": null }, { "creator_type": "author", "first_name": "Kayoko", "last_name": "Tao", "name": null }, { "creator_type": "author", "first_name": "Kazuki", "last_name": "Tanimura", "name": null }, { "creator_type": "author", "first_name": "Kouya", "last_name": "Shiraishi", "name": null }, { "creator_type": "author", "first_name": "Shigehiro", "last_name": "Yagishita", "name": null }, { "creator_type": "author", "first_name": "Shinji", "last_name": "Kohsaka", "name": null }, { "creator_type": "author", "first_name": "Mamoru", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Nobutaka", "last_name": "Kiyokawa", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Goto", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null }, { "creator_type": "author", "first_name": "Akinobu", "last_name": "Hamada", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Mano", "name": null }, { "creator_type": "author", "first_name": "Chitose", "last_name": "Ogawa", "name": null }, { "creator_type": "author", "first_name": "Yosuke", "last_name": "Tanaka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41698-023-00485-7" }, "pmcid": { "normalized": "PMC10710492" }, "pmid": { "normalized": "38071343" } }, "mesh": [], "publication": { "conference_name": null, "date": "2023 Dec 9", "date_precision": "day", "issue": "1", "normalized_date": "2023-12-09", "pages": "132", "proceedings_title": null, "publisher": "", "title": "NPJ precision oncology", "volume": "7", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Promoter swapping of truncated PDGFRB drives Ph-like acute lymphoblastic leukemia.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The volume of medical images stored in hospitals is rapidly increasing; however, the utilization of these accumulated medical images remains limited. Existing content-based medical image retrieval (CBMIR) systems typically require example images, leading to practical limitations, such as the lack of customizable, fine-grained image retrieval, the inability to search without example images, and difficulty in retrieving rare cases. In this paper, we introduce a sketch-based medical image retrieval (SBMIR) system that enables users to find images of interest without the need for example images. The key concept is feature decomposition of medical images, which allows the entire feature of a medical image to be decomposed into and reconstructed from normal and abnormal features. Building on this concept, our SBMIR system provides an easy-to-use two-step graphical user interface: users first select a template image to specify a normal feature and then draw a semantic sketch of the disease on the template image to represent an abnormal feature. The system integrates both types of input to construct a query vector and retrieves reference images. For evaluation, ten healthcare professionals participated in a user test using two datasets. Consequently, our SBMIR system enabled users to overcome previous challenges, including image retrieval based on fine-grained image characteristics, image retrieval without example images, and image retrieval for rare cases. Our SBMIR system provides on-demand, customizable medical image retrieval, thereby expanding the utility of medical image databases.", "classifications": [ { "id": "Hamamoto", "label": "Group Hamamoto", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Kazuma", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Lin", "last_name": "Gu", "name": null }, { "creator_type": "author", "first_name": "Ryuichiro", "last_name": "Hataya", "name": null }, { "creator_type": "author", "first_name": "Takaaki", "last_name": "Mizuno", "name": null }, { "creator_type": "author", "first_name": "Mototaka", "last_name": "Miyake", "name": null }, { "creator_type": "author", "first_name": "Hirokazu", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Masamichi", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Yasuyuki", "last_name": "Takamizawa", "name": null }, { "creator_type": "author", "first_name": "Yukihiro", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Nobuji", "last_name": "Kouno", "name": null }, { "creator_type": "author", "first_name": "Amina", "last_name": "Bolatkan", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Kurose", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Harada", "name": null }, { "creator_type": "author", "first_name": "Ryuji", "last_name": "Hamamoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.media.2023.103060" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "38104401" } }, "mesh": [ { "descriptor": "Algorithms", "descriptor_ui": "D000465", "major_topic": true }, { "descriptor": "Databases, Factual", "descriptor_ui": "D016208", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Information Storage and Retrieval", "descriptor_ui": "D016247", "major_topic": false }, { "descriptor": "Semantics", "descriptor_ui": "D012660", "major_topic": true } ], "publication": { "conference_name": null, "date": "2023 Dec 8", "date_precision": "day", "issue": "", "normalized_date": "2023-12-08", "pages": "103060", "proceedings_title": null, "publisher": "", "title": "Medical image analysis", "volume": "92", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Sketch-based semantic retrieval of medical images.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Angiocrine signals during the development and growth of organs, including the liver, intestine, lung, and bone, are essential components of intercellular communication. The signals elicited during the liver bud stage are critical for vascularization and enhanced during the intercellular communication between the cells negative for KDR (KDR- cells) and the cells positive for KDR (KDR+ cells), which constitute the liver bud. However, the use of a human pluripotent stem cell (hPSC)-derived system has not facilitated the generation of a perfusable vascularized liver organoid that allows elucidation of liver development and has great potential for liver transplantation. This is largely owing to the lack of fundamental understanding to induce angiocrine signals in KDR- and KDR+ cells during the liver bud stage. We hypothesized that mechanical stimuli of cyclic stretching/pushing by the fetal heart adjacent to the liver bud could be the main contributor to promoting angiocrine signals in KDR- and KDR+ cells during the liver bud stage. Here, we show that an organ-on-a-chip platform allows the emulation of an in vivo-like mechanical environment for the liver bud stage in vitro and investigate the role of cyclic mechanical stretching (cMS) to angiocrine signals in KDR- and KDR+ cells derived from hPSCs. RNA sequencing revealed that the expression of genes associated with epithelial-to-mesenchymal transition, including angiocrine signals, such as hepatocyte growth factor (HGF) and matrix metallopeptidase 9 (MMP9), were increased by cMS in co-cultured KDR- and KDR+ cells. The expression and secretions of HGF and MMP9 were increased by 1.98- and 1.69-fold and 3.23- and 3.72-fold with cMS in the co-cultured KDR- and KDR+ cells but were not increased by cMS in the mono-cultured KDR- and KDR+ cells, respectively. Finally, cMS during the liver bud stage did not lead to the dedifferentiation of hepatocytes, as the cells with cMS showed hepatic maker expression (CYP3A4, CYP3A7, ALB, and AAT) and 1.71-fold higher CYP3A activity than the cells without cMS, during 12 day-hepatocyte maturation after halting cMS. Our findings provide new insights into the mechanical factors during the liver bud stage and directions for future improvements in the engineered liver tissue.", "classifications": [ { "id": "Maki", "label": "Group Maki", "parent": "Toyoshima", "type": "group" }, { "id": "Toyoshima", "label": "Team Toyoshima", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Koki", "last_name": "Yoshimoto", "name": null }, { "creator_type": "author", "first_name": "Koichiro", "last_name": "Maki", "name": null }, { "creator_type": "author", "first_name": "Taiji", "last_name": "Adachi", "name": null }, { "creator_type": "author", "first_name": "Ken-Ichiro", "last_name": "Kamei", "name": null } ], "identifiers": { "doi": { "normalized": "10.1089/ten.tea.2023.0148" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "38062736" } }, "mesh": [ { "descriptor": "Cell Culture Techniques", "descriptor_ui": "D018929", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Liver", "descriptor_ui": "D008099", "major_topic": true }, { "descriptor": "Pluripotent Stem Cells", "descriptor_ui": "D039904", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Vascular Endothelial Growth Factor Receptor-2", "descriptor_ui": "D040301", "major_topic": true } ], "publication": { "conference_name": null, "date": "2023 Dec 7", "date_precision": "day", "issue": "", "normalized_date": "2023-12-07", "pages": "", "proceedings_title": null, "publisher": "", "title": "Tissue engineering. Part A", "volume": "", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Cyclic Stretching Enhances Angiocrine Signals at Liver Bud Stage from hPSCs in 2-Dimensional Culture.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "We propose a novel odor-sensing system based on the dynamic response of phospholipid molecular layers for artificial olfaction. Organisms obtain information about their surroundings based on multidimensional information obtained from sniffing, i.e., periodic perturbations. Semiconductor- and receptor-based odor sensors have been developed previously. However, these sensors predominantly identify odors based on one-dimensional information, which limits the type of odor molecule they can identify. Therefore, the development of odor sensors that mimic the olfactory systems of living organisms is useful to overcome this limitation. In this study, we developed a novel odor-sensing system based on the dynamics of phospholipids that responds delicately to chemical substances at room temperature using multidimensional information obtained from periodic perturbations. Odor molecules are periodically supplied to the phospholipid molecular layer as an input sample. The waveform of the surface tension of the phospholipid molecular layer changes depending on the odor molecules and serves as an output. Such characteristic responses originating from the dynamics of odor molecules on the phospholipid molecular layer can be reproduced numerically. The phospholipid molecular layer amplified the information originating from the odor molecule, and the mechanism was evaluated by using surface pressure-area isotherms. This paper offers a platform for an interface-chemistry-based artificial sniffing system as an active sensor and a novel olfactory mechanism via physicochemical responses of the receptor-independent membranes of the organism.", "classifications": [ { "id": "Nagayama", "label": "Group Nagayama", "parent": "Fujiwara", "type": "group" }, { "id": "Fujiwara", "label": "Team Fujiwara", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Mai", "last_name": "Yotsumoto", "name": null }, { "creator_type": "author", "first_name": "Muneyuki", "last_name": "Matsuo", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Kitahata", "name": null }, { "creator_type": "author", "first_name": "Shinobu", "last_name": "Nakanishi", "name": null }, { "creator_type": "author", "first_name": "Mitsuhiro", "last_name": "Denda", "name": null }, { "creator_type": "author", "first_name": "Masaharu", "last_name": "Nagayama", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Nakata", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/acssensors.3c00382" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "38060767" } }, "mesh": [ { "descriptor": "Odorants", "descriptor_ui": "D009812", "major_topic": true }, { "descriptor": "Smell", "descriptor_ui": "D012903", "major_topic": true } ], "publication": { "conference_name": null, "date": "2023 Dec 7", "date_precision": "day", "issue": "", "normalized_date": "2023-12-07", "pages": "", "proceedings_title": null, "publisher": "", "title": "ACS sensors", "volume": "", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Phospholipid Molecular Layer that Enhances Distinction of Odors Based on Artificial Sniffing.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Recently, several studies using cultures of human embryos together with single-cell RNA-seq (scRNA-seq) analyses have revealed differences between humans and mice, necessitating the study of human embryos (1-8). Despite the importance of human embryology, ethical and legal restrictions have limited post-implantation stage studies. Thus, recent efforts have focused on developing in vitro self-organising models using human stem cells (9-17). Here, we report genetic and non-genetic approaches to generate authentic hypoblast cells (nHyC)-known to give rise to one of the two extraembryonic tissues essential for embryonic development-from naive human pluripotent stem cells (hPSCs). Our nHyCs spontaneously assemble with naive hPSCs to form a three-dimensional bilaminar structure (bilaminoids) with a pro-amniotic-like cavity. In the presence of additional naive hPSC-derived analogues of the second extraembryonic tissue, the trophectoderm, the efficiency of bilaminoid formation increases from 20% to 40%, and the epiblast within the bilaminoids continues to develop in response to trophectoderm-secreted IL6. Furthermore, we show that bilaminoids robustly recapitulate the patterning of the anterior-posterior axis and the formation of cells reflecting the pre-gastrula stage, whose emergence can be shaped by genetically manipulating the DKK1/OTX2 hypoblast-like domain. We have thus successfully modelled and revealed the mechanisms by which the two extraembryonic tissues efficiently guide the stage-specific growth and progression of the epiblast as it establishes the post-implantation landmarks of human embryogenesis.", "classifications": [ { "id": "JPMJCR2023", "label": "JPMJCR2023", "researcher": "Fumiko Toyoshima", "type": "grant" }, { "id": "Toyoshima", "label": "Group Toyoshima", "parent": "Toyoshima", "type": "group" }, { "id": "Yamamoto", "label": "Group Yamamoto", "parent": "Toyoshima", "type": "group" }, { "id": "Toyoshima", "label": "Team Toyoshima", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Takumi", "last_name": "Okubo", "name": null }, { "creator_type": "author", "first_name": "Nicolas", "last_name": "Rivron", "name": null }, { "creator_type": "author", "first_name": "Mio", "last_name": "Kabata", "name": null }, { "creator_type": "author", "first_name": "Hideki", "last_name": "Masaki", "name": null }, { "creator_type": "author", "first_name": "Keiko", "last_name": "Kishimoto", "name": null }, { "creator_type": "author", "first_name": "Katsunori", "last_name": "Semi", "name": null }, { "creator_type": "author", "first_name": "May", "last_name": "Nakajima-Koyama", "name": null }, { "creator_type": "author", "first_name": "Haruko", "last_name": "Kunitomi", "name": null }, { "creator_type": "author", "first_name": "Belinda", "last_name": "Kaswandy", "name": null }, { "creator_type": "author", "first_name": "Hideyuki", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Hiromitsu", "last_name": "Nakauchi", "name": null }, { "creator_type": "author", "first_name": "Knut", "last_name": "Woltjen", "name": null }, { "creator_type": "author", "first_name": "Mitinori", "last_name": "Saitou", "name": null }, { "creator_type": "author", "first_name": "Erika", "last_name": "Sasaki", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Yasuhiro", "last_name": "Takashima", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41586-023-06871-2" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "38052228" } }, "mesh": [ { "descriptor": "Amnion", "descriptor_ui": "D000650", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Ectoderm", "descriptor_ui": "D004475", "major_topic": false }, { "descriptor": "Embryo Implantation", "descriptor_ui": "D010064", "major_topic": false }, { "descriptor": "Embryo, Mammalian", "descriptor_ui": "D004622", "major_topic": false }, { "descriptor": "Embryonic Development", "descriptor_ui": "D047108", "major_topic": true }, { "descriptor": "Gastrula", "descriptor_ui": "D005775", "major_topic": false }, { "descriptor": "Germ Layers", "descriptor_ui": "D005855", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Intercellular Signaling Peptides and Proteins", "descriptor_ui": "D036341", "major_topic": false }, { "descriptor": "Interleukin-6", "descriptor_ui": "D015850", "major_topic": false }, { "descriptor": "Otx Transcription Factors", "descriptor_ui": "D051857", "major_topic": false }, { "descriptor": "Pluripotent Stem Cells", "descriptor_ui": "D039904", "major_topic": true } ], "publication": { "conference_name": null, "date": "2023 Dec 5", "date_precision": "day", "issue": "", "normalized_date": "2023-12-05", "pages": "", "proceedings_title": null, "publisher": "", "title": "Nature", "volume": "", "year": 2023 }, "ssbd": { "database": [ "ssbd-database-000379" ], "repository": [ "ssbd-repos-000379" ] }, "title": "Hypoblast from human pluripotent stem cells regulates epiblast development.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Cancer cells inevitably interact with neighboring host tissue-resident cells during the process of metastatic colonization, establishing a metastatic niche to fuel their survival, growth, and invasion. However, the underlying mechanisms in the metastatic niche are yet to be fully elucidated owing to the lack of methodologies for comprehensively studying the mechanisms of cell-cell interactions in the niche. Here, we improve a split green fluorescent protein (GFP)-based genetically encoded system to develop secretory glycosylphosphatidylinositol-anchored reconstitution-activated proteins to highlight intercellular connections (sGRAPHIC) for efficient fluorescent labeling of tissue-resident cells that neighbor on and putatively interact with cancer cells in deep tissues. The sGRAPHIC system enables the isolation of metastatic niche-associated tissue-resident cells for their characterization using a single-cell RNA sequencing platform. We use this sGRAPHIC-leveraged transcriptomic platform to uncover gene expression patterns in metastatic niche-associated hepatocytes in a murine model of liver metastasis. Among the marker genes of metastatic niche-associated hepatocytes, we identify Lgals3, encoding galectin-3, as a potential pro-metastatic factor that accelerates metastatic growth and invasion.", "classifications": [ { "id": "JPMJCR2124", "label": "JPMJCR2124", "researcher": "Hirofumi Shintaku", "type": "grant" }, { "id": "Kuchimaru", "label": "Group Kuchimaru", "parent": "Shintaku", "type": "group" }, { "id": "Shintaku", "label": "Group Shintaku", "parent": "Shintaku", "type": "group" }, { "id": "Shintaku", "label": "Team Shintaku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Misa", "last_name": "Minegishi", "name": null }, { "creator_type": "author", "first_name": "Takahiro", "last_name": "Kuchimaru", "name": null }, { "creator_type": "author", "first_name": "Kaori", "last_name": "Nishikawa", "name": null }, { "creator_type": "author", "first_name": "Takayuki", "last_name": "Isagawa", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Iwano", "name": null }, { "creator_type": "author", "first_name": "Kei", "last_name": "Iida", "name": null }, { "creator_type": "author", "first_name": "Hiromasa", "last_name": "Hara", "name": null }, { "creator_type": "author", "first_name": "Shizuka", "last_name": "Miura", "name": null }, { "creator_type": "author", "first_name": "Marika", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Shigeaki", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Akifumi", "last_name": "Shiomi", "name": null }, { "creator_type": "author", "first_name": "Yo", "last_name": "Mabuchi", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Hamana", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Kishi", "name": null }, { "creator_type": "author", "first_name": "Tatsuyuki", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Daigo", "last_name": "Sawaki", "name": null }, { "creator_type": "author", "first_name": "Shigeru", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Yutaka", "last_name": "Hanazono", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Takahide", "last_name": "Kohro", "name": null }, { "creator_type": "author", "first_name": "Tetsuya", "last_name": "Kadonosono", "name": null }, { "creator_type": "author", "first_name": "Tomomi", "last_name": "Shimogori", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Miyawaki", "name": null }, { "creator_type": "author", "first_name": "Norihiko", "last_name": "Takeda", "name": null }, { "creator_type": "author", "first_name": "Hirofumi", "last_name": "Shintaku", "name": null }, { "creator_type": "author", "first_name": "Shinae", "last_name": "Kizaka-Kondoh", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Nishimura", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41467-023-43855-2" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "38052804" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Communication", "descriptor_ui": "D002450", "major_topic": false }, { "descriptor": "Extracellular Matrix", "descriptor_ui": "D005109", "major_topic": false }, { "descriptor": "Green Fluorescent Proteins", "descriptor_ui": "D049452", "major_topic": false }, { "descriptor": "Hepatocytes", "descriptor_ui": "D022781", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Liver Neoplasms", "descriptor_ui": "D008113", "major_topic": true }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false } ], "publication": { "conference_name": null, "date": "2023 Dec 5", "date_precision": "day", "issue": "1", "normalized_date": "2023-12-05", "pages": "8031", "proceedings_title": null, "publisher": "", "title": "Nature communications", "volume": "14", "year": 2023 }, "ssbd": { "database": [ "ssbd-database-000378" ], "repository": [ "ssbd-repos-000378" ] }, "title": "Secretory GFP reconstitution labeling of neighboring cells interrogates cell-cell interactions in metastatic niches.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Rapid and precise intraoperative diagnosing systems are required for improving surgical outcomes and patient prognosis. Because of the poor quality and time-intensive process of the prevalent frozen section procedure, various intraoperative diagnostic imaging systems have been explored. Microscopy with ultraviolet surface excitation (MUSE) is an inexpensive, maintenance-free, and rapid imaging technique that yields images like thin-sectioned samples without sectioning. However, pathologists find it nearly impossible to assign diagnostic labels to MUSE images of unfixed specimens; thus, AI for intraoperative diagnosis cannot be trained in a supervised learning manner. In this study, we propose a deep-learning pipeline model for lymph node metastasis detection, in which CycleGAN translate MUSE images of unfixed lymph nodes to formalin-fixed paraffin-embedded (FFPE) sample, and diagnostic prediction is performed using deep convolutional neural network trained on FFPE sample images. Our pipeline yielded an average accuracy of 84.6% when using each of the three deep convolutional neural networks, which is a 18.3% increase over the classification-only model without CycleGAN. The modality translation to FFPE sample images using CycleGAN can be applied to various intraoperative diagnostic imaging systems and eliminate the difficulty for pathologists in labeling new modality images in clinical sites. We anticipate our pipeline to be a starting point for accurate rapid intraoperative diagnostic systems for new imaging modalities, leading to healthcare quality improvement.", "classifications": [ { "id": "Tanaka", "label": "Group Tanaka", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Junya", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Matsumoto", "name": null }, { "creator_type": "author", "first_name": "Ryuta", "last_name": "Nakao", "name": null }, { "creator_type": "author", "first_name": "Hideo", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Hajime", "last_name": "Nagahara", "name": null }, { "creator_type": "author", "first_name": "Hirohiko", "last_name": "Niioka", "name": null }, { "creator_type": "author", "first_name": "Tetsuro", "last_name": "Takamatsu", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41598-023-48319-7" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "38049475" } }, "mesh": [ { "descriptor": "Alprostadil", "descriptor_ui": "D000527", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Lymphatic Metastasis", "descriptor_ui": "D008207", "major_topic": false }, { "descriptor": "Microscopy, Fluorescence", "descriptor_ui": "D008856", "major_topic": false }, { "descriptor": "Neural Networks, Computer", "descriptor_ui": "D016571", "major_topic": true } ], "publication": { "conference_name": null, "date": "2023 Dec 4", "date_precision": "day", "issue": "1", "normalized_date": "2023-12-04", "pages": "21363", "proceedings_title": null, "publisher": "", "title": "Scientific reports", "volume": "13", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Deep UV-excited fluorescence microscopy installed with CycleGAN-assisted image translation enhances precise detection of lymph node metastasis towards rapid intraoperative diagnosis.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The maternal liver is challenged by metabolic demands throughout pregnancy. However, hepatocyte dynamics and their physiological significance in pregnancy remain unclear. Here, we show in mice that hepatocyte proliferation is spatiotemporally regulated in each liver lobular zone during pregnancy, with transient proliferation of periportal and pericentral hepatocytes during mid and late gestation, respectively. Using adeno-associated virus (AAV)-8-mediated expression of the cell cycle inhibitor p21 in hepatocytes, we show that inhibition of hepatocyte proliferation during mid, but not late, gestation impairs liver growth. Transcriptionally, genes involved in glucose/glycogen metabolism are downregulated in late pregnancy when midgestational hepatocyte proliferation is attenuated. In addition, hepatic glycogen storage is abolished, with concomitant elevated blood glucose concentrations, glucose intolerance, placental glycogen deposition, and fetal overgrowth. Laser capture microdissection and RNA-seq analysis of each liver lobular zone show zone-specific changes in the transcriptome during pregnancy and identify genes that are periportally expressed at midgestation, including the hyaluronan-mediated motility receptor (Hmmr). Knockdown of Hmmr in hepatocytes by AAV8-shHmmr suppresses periportal hepatocyte proliferation at midgestation and induces impaired hepatic glycogen storage, glucose intolerance, placental glycogen deposition and fetal overgrowth. Our results suggest that periportal hepatocyte proliferation during midgestation is critical for maternal glycogen metabolism and fetal size.", "classifications": [ { "id": "JPMJCR2023", "label": "JPMJCR2023", "researcher": "Fumiko Toyoshima", "type": "grant" }, { "id": "Toyoshima", "label": "Group Toyoshima", "parent": "Toyoshima", "type": "group" }, { "id": "Yamamoto", "label": "Group Yamamoto", "parent": "Toyoshima", "type": "group" }, { "id": "Toyoshima", "label": "Team Toyoshima", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Satoshi", "last_name": "Kozuki", "name": null }, { "creator_type": "author", "first_name": "Mio", "last_name": "Kabata", "name": null }, { "creator_type": "author", "first_name": "Satoko", "last_name": "Sakurai", "name": null }, { "creator_type": "author", "first_name": "Keiko", "last_name": "Iwaisako", "name": null }, { "creator_type": "author", "first_name": "Tomomi", "last_name": "Nishimura", "name": null }, { "creator_type": "author", "first_name": "Masakazu", "last_name": "Toi", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Fumiko", "last_name": "Toyoshima", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s42003-023-05614-3" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "38049528" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Proliferation", "descriptor_ui": "D049109", "major_topic": false }, { "descriptor": "Diabetes, Gestational", "descriptor_ui": "D016640", "major_topic": true }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Fetal Macrosomia", "descriptor_ui": "D005320", "major_topic": false }, { "descriptor": "Glucose", "descriptor_ui": "D005947", "major_topic": false }, { "descriptor": "Glucose Intolerance", "descriptor_ui": "D018149", "major_topic": true }, { "descriptor": "Glycogen", "descriptor_ui": "D006003", "major_topic": false }, { "descriptor": "Hepatocytes", "descriptor_ui": "D022781", "major_topic": false }, { "descriptor": "Homeostasis", "descriptor_ui": "D006706", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Liver Glycogen", "descriptor_ui": "D008112", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Placenta", "descriptor_ui": "D010920", "major_topic": false }, { "descriptor": "Pregnancy", "descriptor_ui": "D011247", "major_topic": false } ], "publication": { "conference_name": null, "date": "2023 Dec 4", "date_precision": "day", "issue": "1", "normalized_date": "2023-12-04", "pages": "1226", "proceedings_title": null, "publisher": "", "title": "Communications biology", "volume": "6", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Periportal hepatocyte proliferation at midgestation governs maternal glucose homeostasis in mice.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Xenopus laevis is a widely used model organism in developmental and regeneration studies. Despite several reports regarding targeted integration techniques in Xenopus, there is still room for improvement of them, especially in creating reporter lines that rely on endogenous regulatory enhancers/promoters. We developed a CRISPR-Cas9-based simple method to efficiently introduce a fluorescent protein gene into 5' untranslated regions (5'UTRs) of target genes in Xenopus laevis. A donor plasmid DNA encoding an enhanced green fluorescent protein (eGFP) flanked by a genomic fragment ranging from 66 bp to 878 bp including target 5'UTR was co-injected into fertilized eggs with a single guide RNA and Cas9 protein. Injections for krt12.2.L, myod1.S, sox2.L or brevican.S resulted in embryos expressing eGFP fluorescence in a tissue-specific manner, recapitulating endogenous expression of target genes. Integrations of the donor DNA into the target regions were examined by genotyping PCR for the eGFP-expressing embryos. The rate of embryos expressing the specific eGFP varied from 2.1% to 13.2% depending on the target locus and length of the genomic fragment in the donor plasmids. Germline transmission of an integrated DNA was observed. This simple method provides a powerful tool for exploring gene expression and function in developmental and regeneration research in X. laevis.", "classifications": [ { "id": "JPMJCR2025", "label": "JPMJCR2025", "researcher": "Yoshihiro Morishita", "type": "grant" }, { "id": "Morishita", "label": "Group Morishita", "parent": "Morishita", "type": "group" }, { "id": "Suzuki", "label": "Group Suzuki", "parent": "Morishita", "type": "group" }, { "id": "Morishita", "label": "Team Morishita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Makoto", "last_name": "Mochii", "name": null }, { "creator_type": "author", "first_name": "Kai", "last_name": "Akizuki", "name": null }, { "creator_type": "author", "first_name": "Hero", "last_name": "Ossaka", "name": null }, { "creator_type": "author", "first_name": "Norie", "last_name": "Kagawa", "name": null }, { "creator_type": "author", "first_name": "Yoshihiko", "last_name": "Umesono", "name": null }, { "creator_type": "author", "first_name": "Ken-Ichi T.", "last_name": "Suzuki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.ydbio.2023.11.010" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "38052295" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "CRISPR-Cas Systems", "descriptor_ui": "D064113", "major_topic": true }, { "descriptor": "DNA", "descriptor_ui": "D004247", "major_topic": false }, { "descriptor": "Gene Expression", "descriptor_ui": "D015870", "major_topic": false }, { "descriptor": "RNA, Guide, CRISPR-Cas Systems", "descriptor_ui": "D000094704", "major_topic": true }, { "descriptor": "Xenopus laevis", "descriptor_ui": "D014982", "major_topic": false } ], "publication": { "conference_name": null, "date": "2023 Dec 3", "date_precision": "day", "issue": "", "normalized_date": "2023-12-03", "pages": "S0012-1606(23)00200-2", "proceedings_title": null, "publisher": "", "title": "Developmental biology", "volume": "", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "A CRISPR-Cas9-mediated versatile method for targeted integration of a fluorescent protein gene to visualize endogenous gene expression in Xenopus laevis.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Half of the individuals who wear contact lenses use reusable lenses that require proper care. Improper contact lens (CL) care and using inadequate disinfecting solutions can lead to lens contamination, CL-related microbial keratitis, and Acanthamoeba keratitis. Oxidative disinfecting solutions, such as hydrogen peroxide, show higher efficacy than multipurpose solutions. Povidone-iodine (PVP-I), an oxidative disinfectant used in ophthalmic surgery, has been proven to be safe and effective. The PVP-I system, a CL disinfecting solution developed in Japan, has demonstrated excellent antimicrobial and antiviral properties. Although CL discomfort does not have a risk of ocular disorders with poor visual prognosis, such as keratitis, CL discomfort can still lead to lens dropout and thus needs to be addressed. To mitigate CL discomfort, it is essential to use disinfecting solutions containing surfactants and wetting agents that improve wettability of the lens surface. A CL solution containing hyaluronic acid derivatives (HADs) as wetting agents that permanently adhere to the lens surface to improve wettability of the lens surface was developed in Japan. There is potential for HAD to be integrated into various solutions. This article reviews the efficacy of novel PVP-I-based disinfecting solution and HAD wetting agents.", "classifications": [ { "id": "Suzuki", "label": "Group Suzuki", "parent": "Takekawa", "type": "group" }, { "id": "Takekawa", "label": "Team Takekawa", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Takashi", "last_name": "Itokawa", "name": null }, { "creator_type": "author", "first_name": "Katsuhide", "last_name": "Yamasaki", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Shizuka", "last_name": "Koh", "name": null } ], "identifiers": { "doi": { "normalized": "10.1097/icl.0000000000001060" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "38019569" } }, "mesh": [ { "descriptor": "Acanthamoeba Keratitis", "descriptor_ui": "D015823", "major_topic": true }, { "descriptor": "Contact Lens Solutions", "descriptor_ui": "D018639", "major_topic": false }, { "descriptor": "Contact Lenses", "descriptor_ui": "D003261", "major_topic": true }, { "descriptor": "Disinfectants", "descriptor_ui": "D004202", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Japan", "descriptor_ui": "D007564", "major_topic": false }, { "descriptor": "Povidone-Iodine", "descriptor_ui": "D011206", "major_topic": false }, { "descriptor": "Wetting Agents", "descriptor_ui": "D014906", "major_topic": false } ], "publication": { "conference_name": null, "date": "2023 Nov 29", "date_precision": "day", "issue": "", "normalized_date": "2023-11-29", "pages": "", "proceedings_title": null, "publisher": "", "title": "Eye & contact lens", "volume": "", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Advances in Contact Lens Care Solutions: PVP-I Disinfectant and HAD Wetting Agents From Japan.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Ratiometric Raman analysis of reversible thia-Michael reactions was achieved using alpha-cyanoacrylic acid (alphaCNA) derivatives. Among alphaCNAs, the smallest derivative, ThioRas (molecular weight: 167 g mol(-1)), and its glutathione adduct were simultaneously detected in various subcellular locations using Raman microscopy.", "classifications": [ { "id": "Fujita", "label": "Group Fujita", "parent": "Fujita", "type": "group" }, { "id": "Nakabayashi", "label": "Group Nakabayashi", "parent": "Nishida", "type": "group" }, { "id": "Sodeoka", "label": "Group Sodeoka", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Yamakoshi", "name": null }, { "creator_type": "author", "first_name": "Daiki", "last_name": "Shibata", "name": null }, { "creator_type": "author", "first_name": "Kazuki", "last_name": "Bando", "name": null }, { "creator_type": "author", "first_name": "Shinji", "last_name": "Kajimoto", "name": null }, { "creator_type": "author", "first_name": "Aki", "last_name": "Kohyama", "name": null }, { "creator_type": "author", "first_name": "Syusuke", "last_name": "Egoshi", "name": null }, { "creator_type": "author", "first_name": "Kosuke", "last_name": "Dodo", "name": null }, { "creator_type": "author", "first_name": "Yoshiharu", "last_name": "Iwabuchi", "name": null }, { "creator_type": "author", "first_name": "Mikiko", "last_name": "Sodeoka", "name": null }, { "creator_type": "author", "first_name": "Katsumasa", "last_name": "Fujita", "name": null }, { "creator_type": "author", "first_name": "Takakazu", "last_name": "Nakabayashi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1039/d3cc05015g" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "37986604" } }, "mesh": [], "publication": { "conference_name": null, "date": "2023 Nov 21", "date_precision": "day", "issue": "", "normalized_date": "2023-11-21", "pages": "", "proceedings_title": null, "publisher": "", "title": "Chemical communications (Cambridge, England)", "volume": "", "year": 2023 }, "ssbd": { "database": [ "ssbd-database-000385" ], "repository": [ "ssbd-repos-000385" ] }, "title": "Ratiometric analysis of reversible thia-Michael reactions using nitrile-tagged molecules by Raman microscopy.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Gastrointestinal tract organs harbor reserve cells, which are endowed with cellular plasticity and regenerate functional units in response to tissue damage. However, whether the reserve cells in gastrointestinal tract exist as long-term quiescent cells remain incompletely understood. In the present study, we systematically examine H2b-GFP label-retaining cells and identify a long-term slow-cycling population in the gastric corpus but not in other gastrointestinal organs. The label-retaining cells, which reside near the basal layers of the corpus, comprise a subpopulation of chief cells. The identified quiescent cells exhibit induction of Atf4 and its target genes including Atf3, a marker of paligenosis, and activation of the unfolded protein response, but do not show elevated expression of Troy, Lgr5, or Mist. External damage to the gastric mucosa induced by indomethacin treatment triggers proliferation of the quiescent Atf4(+) population, indicating that the gastric corpus harbors a specific cell population that is primed to facilitate stomach regeneration.", "classifications": [ { "id": "Okamoto", "label": "Group Okamoto", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Daisuke", "last_name": "Shiokawa", "name": null }, { "creator_type": "author", "first_name": "Hiroaki", "last_name": "Sakai", "name": null }, { "creator_type": "author", "first_name": "Miho", "last_name": "Koizumi", "name": null }, { "creator_type": "author", "first_name": "Yoshie", "last_name": "Okimoto", "name": null }, { "creator_type": "author", "first_name": "Yutaro", "last_name": "Mori", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Kanda", "name": null }, { "creator_type": "author", "first_name": "Hirokazu", "last_name": "Ohata", "name": null }, { "creator_type": "author", "first_name": "Hiroaki", "last_name": "Honda", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Okamoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s42003-023-05550-2" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "37985874" } }, "mesh": [ { "descriptor": "Chief Cells, Gastric", "descriptor_ui": "D019872", "major_topic": true }, { "descriptor": "Epithelial Cells", "descriptor_ui": "D004847", "major_topic": false }, { "descriptor": "Gastric Mucosa", "descriptor_ui": "D005753", "major_topic": false }, { "descriptor": "Stem Cells", "descriptor_ui": "D013234", "major_topic": false }, { "descriptor": "Stomach", "descriptor_ui": "D013270", "major_topic": false } ], "publication": { "conference_name": null, "date": "2023 Nov 20", "date_precision": "day", "issue": "1", "normalized_date": "2023-11-20", "pages": "1183", "proceedings_title": null, "publisher": "", "title": "Communications biology", "volume": "6", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Elevated stress response marks deeply quiescent reserve cells of gastric chief cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Our knowledge of the regulatory mechanisms that govern the replication of the rubella virus (RV) in human cells is limited. To gain insight into the host-pathogen interaction, we conducted a loss-of-function screening using the CRISPR-Cas9 system in the human placenta-derived JAR cells. We identified sphingomyelin synthase 1 (SGMS1 or SMS1) as a susceptibility factor for RV infection. Genetic knockout of SGMS1 rendered JAR cells resistant to infection by RV. The re-introduction of SGMS1 restored cellular susceptibility to RV infection. The restricted step of RV infection was post-endocytosis processes associated with the endosomal acidification. In the late phase of the RV replication cycle, the maintenance of viral persistence was disrupted, partly due to the attenuated viral gene expression. Our results shed light on the unique regulation of RV replication by a host factor during the early and late phases of viral life cycle.", "classifications": [ { "id": "Yusa", "label": "Group Yusa", "parent": "Eiraku", "type": "group" }, { "id": "Eiraku", "label": "Team Eiraku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Mayuko", "last_name": "Yagi", "name": null }, { "creator_type": "author", "first_name": "Minami", "last_name": "Hama", "name": null }, { "creator_type": "author", "first_name": "Sayaka", "last_name": "Ichii", "name": null }, { "creator_type": "author", "first_name": "Yurie", "last_name": "Nakashima", "name": null }, { "creator_type": "author", "first_name": "Daiki", "last_name": "Kanbayashi", "name": null }, { "creator_type": "author", "first_name": "Takako", "last_name": "Kurata", "name": null }, { "creator_type": "author", "first_name": "Kosuke", "last_name": "Yusa", "name": null }, { "creator_type": "author", "first_name": "Jun", "last_name": "Komano", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.isci.2023.108267" }, "pmcid": { "normalized": "PMC10654604" }, "pmid": { "normalized": "38026182" } }, "mesh": [], "publication": { "conference_name": null, "date": "2023 Nov 17", "date_precision": "day", "issue": "11", "normalized_date": "2023-11-17", "pages": "108267", "proceedings_title": null, "publisher": "", "title": "iScience", "volume": "26", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Sphingomyelin synthase 1 supports two steps of rubella virus life cycle.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "OBJECTIVES: While chondrocytes have mitochondria, they receive little O(2) from the bloodstream. Sulfur respiration, an essential energy production system in mitochondria, uses supersulfides instead of O(2). Supersulfides are inorganic and organic sulfides with catenated sulfur atoms and are primarily produced by cysteinyl tRNA synthetase-2 (CARS2). Here, we investigated the role of supersulfides in chondrocyte proliferation and bone growth driven by growth plate chondrocyte proliferation. METHODS: We examined the effects of NaHS, an HS(-)/H(2)S donor, and cystine, the cellular source of cysteine, on the proliferation of mouse primary chondrocytes and growth of embryonic mouse tibia in vitro. We also examined the effect of RNA interference acting on the Cars2 gene on chondrocyte proliferation in the presence of cystine. RESULTS: NaHS (30 mumol/L) enhanced tibia longitudinal growth in vitro with expansion of the proliferating zone of their growth plates. While NaHS (30 mumol/L) also promoted chondrocyte proliferation only under normoxic conditions (20 % O(2)), cystine (0.5 mmol/L) promoted it under both normoxic and hypoxic (2 % O(2)) conditions. Cars2 gene knockdown abrogated the ability of cystine (0.5 mmol/L) to promote chondrocyte proliferation under normoxic conditions, indicating that supersulfides produced by CARS2 were responsible for the cystine-dependent promotion of bone growth. CONCLUSIONS: The presented results indicate that supersulfides play a vital role in bone growth achieved by chondrocyte proliferation in the growth plates driven by sulfur respiration.", "classifications": [ { "id": "Akaike", "label": "Group Akaike", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yuji", "last_name": "Sasama", "name": null }, { "creator_type": "author", "first_name": "Kentaro", "last_name": "Yoshimura", "name": null }, { "creator_type": "author", "first_name": "Marie", "last_name": "Hoshino", "name": null }, { "creator_type": "author", "first_name": "Kiyohito", "last_name": "Sasa", "name": null }, { "creator_type": "author", "first_name": "Takaaki", "last_name": "Akaike", "name": null }, { "creator_type": "author", "first_name": "Masanobu", "last_name": "Morita", "name": null }, { "creator_type": "author", "first_name": "Kazuyoshi", "last_name": "Baba", "name": null }, { "creator_type": "author", "first_name": "Tatsuo", "last_name": "Shirota", "name": null }, { "creator_type": "author", "first_name": "Yoichi", "last_name": "Miyamoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.job.2023.11.004" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "37979656" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Bone Development", "descriptor_ui": "D001846", "major_topic": false }, { "descriptor": "Cell Proliferation", "descriptor_ui": "D049109", "major_topic": false }, { "descriptor": "Chondrocytes", "descriptor_ui": "D019902", "major_topic": true }, { "descriptor": "Cystine", "descriptor_ui": "D003553", "major_topic": false }, { "descriptor": "Growth Plate", "descriptor_ui": "D006132", "major_topic": true }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Sulfur", "descriptor_ui": "D013455", "major_topic": false } ], "publication": { "conference_name": null, "date": "2023 Nov 16", "date_precision": "day", "issue": "", "normalized_date": "2023-11-16", "pages": "S1349-0079(23)00185-8", "proceedings_title": null, "publisher": "", "title": "Journal of oral biosciences", "volume": "", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Supersulfides support bone growth by promoting chondrocyte proliferation in the growth plates.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The heterogeneity of cancer stem cells (CSCs) within tumors presents a challenge in therapeutic targeting. To decipher the cellular plasticity that fuels phenotypic heterogeneity, we undertook single-cell transcriptomics analysis in triple-negative breast cancer (TNBC) to identify subpopulations in CSCs. We found a subpopulation of CSCs with ancestral features that is marked by FXYD domain-containing ion transport regulator 3 (FXYD3), a component of the Na+/K+ pump. Accordingly, FXYD3+ CSCs evolve and proliferate, while displaying traits of alveolar progenitors that are normally induced during pregnancy. Clinically, FXYD3+ CSCs were persistent during neoadjuvant chemotherapy, hence linking them to drug-tolerant persisters (DTPs) and identifying them as crucial therapeutic targets. Importantly, FXYD3+ CSCs were sensitive to senolytic Na+/K+ pump inhibitors, such as cardiac glycosides. Together, our data indicate that FXYD3+ CSCs with ancestral features are drivers of plasticity and chemoresistance in TNBC. Targeting the Na+/K+ pump could be an effective strategy to eliminate CSCs with ancestral and DTP features that could improve TNBC prognosis.", "classifications": [ { "id": "Okamoto", "label": "Group Okamoto", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Mengjiao", "last_name": "Li", "name": null }, { "creator_type": "author", "first_name": "Tatsunori", "last_name": "Nishimura", "name": null }, { "creator_type": "author", "first_name": "Yasuto", "last_name": "Takeuchi", "name": null }, { "creator_type": "author", "first_name": "Tsunaki", "last_name": "Hongu", "name": null }, { "creator_type": "author", "first_name": "Yuming", "last_name": "Wang", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Shiokawa", "name": null }, { "creator_type": "author", "first_name": "Kang", "last_name": "Wang", "name": null }, { "creator_type": "author", "first_name": "Haruka", "last_name": "Hirose", "name": null }, { "creator_type": "author", "first_name": "Asako", "last_name": "Sasahara", "name": null }, { "creator_type": "author", "first_name": "Masao", "last_name": "Yano", "name": null }, { "creator_type": "author", "first_name": "Satoko", "last_name": "Ishikawa", "name": null }, { "creator_type": "author", "first_name": "Masafumi", "last_name": "Inokuchi", "name": null }, { "creator_type": "author", "first_name": "Tetsuo", "last_name": "Ota", "name": null }, { "creator_type": "author", "first_name": "Masahiko", "last_name": "Tanabe", "name": null }, { "creator_type": "author", "first_name": "Kei-Ichiro", "last_name": "Tada", "name": null }, { "creator_type": "author", "first_name": "Tetsu", "last_name": "Akiyama", "name": null }, { "creator_type": "author", "first_name": "Xi", "last_name": "Cheng", "name": null }, { "creator_type": "author", "first_name": "Chia-Chi", "last_name": "Liu", "name": null }, { "creator_type": "author", "first_name": "Toshinari", "last_name": "Yamashita", "name": null }, { "creator_type": "author", "first_name": "Sumio", "last_name": "Sugano", "name": null }, { "creator_type": "author", "first_name": "Yutaro", "last_name": "Uchida", "name": null }, { "creator_type": "author", "first_name": "Tomoki", "last_name": "Chiba", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Asahara", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Nakagawa", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Yohei", "last_name": "Miyagi", "name": null }, { "creator_type": "author", "first_name": "Teppei", "last_name": "Shimamura", "name": null }, { "creator_type": "author", "first_name": "Luis Augusto E.", "last_name": "Nagai", "name": null }, { "creator_type": "author", "first_name": "Akinori", "last_name": "Kanai", "name": null }, { "creator_type": "author", "first_name": "Manami", "last_name": "Katoh", "name": null }, { "creator_type": "author", "first_name": "Seitaro", "last_name": "Nomura", "name": null }, { "creator_type": "author", "first_name": "Ryuichiro", "last_name": "Nakato", "name": null }, { "creator_type": "author", "first_name": "Yutaka", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Arinobu", "last_name": "Tojo", "name": null }, { "creator_type": "author", "first_name": "Dominic C.", "last_name": "Voon", "name": null }, { "creator_type": "author", "first_name": "Seishi", "last_name": "Ogawa", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Okamoto", "name": null }, { "creator_type": "author", "first_name": "Theodoros", "last_name": "Foukakis", "name": null }, { "creator_type": "author", "first_name": "Noriko", "last_name": "Gotoh", "name": null } ], "identifiers": { "doi": { "normalized": "10.1172/jci166666" }, "pmcid": { "normalized": "PMC10645391" }, "pmid": { "normalized": "37966117" } }, "mesh": [ { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Membrane Proteins", "descriptor_ui": "D008565", "major_topic": false }, { "descriptor": "Neoplasm Proteins", "descriptor_ui": "D009363", "major_topic": false }, { "descriptor": "Neoplastic Stem Cells", "descriptor_ui": "D014411", "major_topic": false }, { "descriptor": "Triple Negative Breast Neoplasms", "descriptor_ui": "D064726", "major_topic": true } ], "publication": { "conference_name": null, "date": "2023 Nov 15", "date_precision": "day", "issue": "22", "normalized_date": "2023-11-15", "pages": "", "proceedings_title": null, "publisher": "", "title": "The Journal of clinical investigation", "volume": "133", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "FXYD3 functionally demarcates an ancestral breast cancer stem cell subpopulation with features of drug-tolerant persisters.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "In vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) are 2 major assisted reproductive techniques (ARTs) used widely to treat infertility. Recently, spermatogonial transplantation emerged as a new ART to restore fertility to young patients with cancer after cancer therapy. To examine the influence of germ cell manipulation on behavior of offspring, we produced F1 offspring by a combination of two ARTs, spermatogonial transplantation and ICSI. When these animals were compared with F1 offspring produced by ICSI using fresh wild-type sperm, not only spermatogonial transplantation-ICSI mice but also ICSI-only control mice exhibited behavioral abnormalities, which persisted in the F2 generation. Furthermore, although these F1 offspring appeared normal, F2 offspring produced by IVF using F1 sperm and wild-type oocytes showed various types of congenital abnormalities, including anophthalmia, hydrocephalus, and missing limbs. Therefore, ARTs can induce morphological and functional defects in mice, some of which become evident only after germline transmission.", "classifications": [ { "id": "Yamamoto", "label": "Group Yamamoto", "parent": "Toyoshima", "type": "group" }, { "id": "Toyoshima", "label": "Team Toyoshima", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Mito", "last_name": "Kanatsu-Shinohara", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Shiromoto", "name": null }, { "creator_type": "author", "first_name": "Narumi", "last_name": "Ogonuki", "name": null }, { "creator_type": "author", "first_name": "Kimiko", "last_name": "Inoue", "name": null }, { "creator_type": "author", "first_name": "Satoko", "last_name": "Hattori", "name": null }, { "creator_type": "author", "first_name": "Kento", "last_name": "Miura", "name": null }, { "creator_type": "author", "first_name": "Naomi", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Ayumi", "last_name": "Hasegawa", "name": null }, { "creator_type": "author", "first_name": "Keiji", "last_name": "Mochida", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Tsuyoshi", "last_name": "Miyakawa", "name": null }, { "creator_type": "author", "first_name": "Atsuo", "last_name": "Ogura", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Shinohara", "name": null } ], "identifiers": { "doi": { "normalized": "10.1172/jci170140" }, "pmcid": { "normalized": "PMC10645388" }, "pmid": { "normalized": "37966118" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Fertilization in Vitro", "descriptor_ui": "D005307", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Infertility", "descriptor_ui": "D007246", "major_topic": true }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Neoplasms", "descriptor_ui": "D009369", "major_topic": true }, { "descriptor": "Semen", "descriptor_ui": "D012661", "major_topic": false }, { "descriptor": "Sperm Injections, Intracytoplasmic", "descriptor_ui": "D020554", "major_topic": false } ], "publication": { "conference_name": null, "date": "2023 Nov 15", "date_precision": "day", "issue": "22", "normalized_date": "2023-11-15", "pages": "", "proceedings_title": null, "publisher": "", "title": "The Journal of clinical investigation", "volume": "133", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Intracytoplasmic sperm injection induces transgenerational abnormalities in mice.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Sulfur is essential in the inception of life and crucial for maintaining human health. This mineral is primarily supplied through the intake of proteins and is used for synthesizing various sulfur-containing biomolecules. Recent research has highlighted the biological significance of endogenous supersulfides, which include reactive persulfide species and sulfur catenated residues in thiol and proteins. Ingestion of exogenous sulfur compounds is essential for endogenous supersulfide production. However, the content and composition of supersulfides in foods remain unclear. This study investigated the supersulfide profiles of protein-rich foods, including edible animal meat and beans. Quantification of the supersulfide content revealed that natto, chicken liver, and bean sprouts contained abundant supersulfides. In general, the supersulfide content in beans and their derivatives was higher than that in animal meat. The highest proportion (2.15 %) was detected in natto, a traditional Japanese fermented soybean dish. These results suggest that the abundance of supersulfides, especially in foods like natto and bean sprouts, may contribute to their health-promoting properties. Our findings may have significant biological implications and warrant developing novel dietary intervention for the human health-promoting effects of dietary supersulfides abundantly present in protein-rich foods such as natto and bean sprouts.", "classifications": [ { "id": "JPMJCR2024", "label": "JPMJCR2024", "researcher": "Motohiro Nishida", "type": "grant" }, { "id": "Akaike", "label": "Group Akaike", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Group Nishida", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Shingo", "last_name": "Kasamatsu", "name": null }, { "creator_type": "author", "first_name": "Ayaka", "last_name": "Kinno", "name": null }, { "creator_type": "author", "first_name": "Chiharu", "last_name": "Miura", "name": null }, { "creator_type": "author", "first_name": "Jun-Ichi", "last_name": "Hishiyama", "name": null }, { "creator_type": "author", "first_name": "Kensuke", "last_name": "Fukui", "name": null }, { "creator_type": "author", "first_name": "Shoji", "last_name": "Kure", "name": null }, { "creator_type": "author", "first_name": "Kazunobu", "last_name": "Tsumura", "name": null }, { "creator_type": "author", "first_name": "Tomoaki", "last_name": "Ida", "name": null }, { "creator_type": "author", "first_name": "Tetsuro", "last_name": "Matsunaga", "name": null }, { "creator_type": "author", "first_name": "Takaaki", "last_name": "Akaike", "name": null }, { "creator_type": "author", "first_name": "Hideshi", "last_name": "Ihara", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.ab.2023.115392" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "37967784" } }, "mesh": [ { "descriptor": "Glycine max", "descriptor_ui": "D013025", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Meat", "descriptor_ui": "D008460", "major_topic": false }, { "descriptor": "Soy Foods", "descriptor_ui": "D045730", "major_topic": true }, { "descriptor": "Sulfur", "descriptor_ui": "D013455", "major_topic": false } ], "publication": { "conference_name": null, "date": "2023 Nov 13", "date_precision": "day", "issue": "", "normalized_date": "2023-11-13", "pages": "115392", "proceedings_title": null, "publisher": "", "title": "Analytical biochemistry", "volume": "685", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Quantitative profiling of supersulfides naturally occurring in dietary meats and beans.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Attention-deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) are associated with attentional impairments, with both commonalities and differences in the nature of their attention deficits. This study aimed to investigate the neural correlates of ADHD and ASD traits in healthy individuals, focusing on the functional connectivity (FC) of attention-related large-scale brain networks (LSBNs). The participants were 61 healthy individuals (30 men; age, 21.9 +/- 1.9 years). The Adult ADHD Self-Report Scale (ASRS) and Autism Spectrum Quotient (AQ) were administered as indicators of ADHD and ASD traits, respectively. Performance in the continuous performance test (CPT) was used as a behavioural measure of sustained attentional function. Functional magnetic resonance imaging scans were performed during the resting state (Rest) and auditory oddball task (Odd). Considering the critical role in attention processing, we focused our analyses on the default mode (DMN), frontoparietal (FPN), and salience (SN) networks. Region of interest (ROI)-to-ROI analyses (false discovery rate < 0.05) were performed to determine relationships between psychological measures with within-network FC (DMN, FPN, and SN) as well as with between-network FC (DMN-FPN, DMN-SN, and FPN-SN). ASRS scores, but not AQ scores, were correlated with less frequent commission errors and shorter reaction times in the CPT. During Odd, significant positive correlations with ASRS were demonstrated in multiple FCs within DMN, while significant positive correlations with AQ were demonstrated in multiple FCs within FPN. AQs were negatively correlated with FPN-SN FCs. During Rest, AQs were negatively and positively correlated with one FC within the SN and multiple FCs between the DMN and SN, respectively. These findings of the ROI-to-ROI analysis were only partially replicated in a split-half replication analysis, a replication analysis with open-access data sets, and a replication analysis with a structure-based atlas. The better CPT performance by individuals with subclinical ADHD traits suggests positive effects of these traits on sustained attention. Differential associations between LSBN FCs and ASD/ADHD traits corroborate the notion of differences in sustained and selective attention between clinical ADHD and ASD.", "classifications": [ { "id": "Fujiwara", "label": "Group Fujiwara", "parent": "Fujiwara", "type": "group" }, { "id": "Fujiwara", "label": "Team Fujiwara", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Risa", "last_name": "Hirata", "name": null }, { "creator_type": "author", "first_name": "Sayaka", "last_name": "Yoshimura", "name": null }, { "creator_type": "author", "first_name": "Key", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Morio", "last_name": "Aki", "name": null }, { "creator_type": "author", "first_name": "Mami", "last_name": "Shibata", "name": null }, { "creator_type": "author", "first_name": "Tsukasa", "last_name": "Ueno", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Miyagi", "name": null }, { "creator_type": "author", "first_name": "Naoya", "last_name": "Oishi", "name": null }, { "creator_type": "author", "first_name": "Toshiya", "last_name": "Murai", "name": null }, { "creator_type": "author", "first_name": "Hironobu", "last_name": "Fujiwara", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41598-023-47034-7" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "37957246" } }, "mesh": [ { "descriptor": "Attention Deficit Disorder with Hyperactivity", "descriptor_ui": "D001289", "major_topic": true }, { "descriptor": "Autism Spectrum Disorder", "descriptor_ui": "D000067877", "major_topic": true }, { "descriptor": "Autistic Disorder", "descriptor_ui": "D001321", "major_topic": true }, { "descriptor": "Brain", "descriptor_ui": "D001921", "major_topic": false }, { "descriptor": "Brain Mapping", "descriptor_ui": "D001931", "major_topic": false }, { "descriptor": "East Asian People", "descriptor_ui": "D000095225", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Magnetic Resonance Imaging", "descriptor_ui": "D008279", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Neural Pathways", "descriptor_ui": "D009434", "major_topic": false }, { "descriptor": "Young Adult", "descriptor_ui": "D055815", "major_topic": false } ], "publication": { "conference_name": null, "date": "2023 Nov 13", "date_precision": "day", "issue": "1", "normalized_date": "2023-11-13", "pages": "19724", "proceedings_title": null, "publisher": "", "title": "Scientific reports", "volume": "13", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Differences between subclinical attention-deficit/hyperactivity and autistic traits in default mode, salience, and frontoparietal network connectivities in young adult Japanese.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Many patients with non-small cell lung cancer do not receive guideline-recommended, biomarker-directed therapy, despite the potential for improved clinical outcomes. Access to timely, accurate, and comprehensive molecular profiling, including targetable protein overexpression, is essential to allow fully informed treatment decisions to be taken. In turn, this requires optimal tissue management to protect and maximize the use of this precious finite resource. Here, a group of leading thoracic pathologists recommend factors to consider for optimal tissue management. Starting from when lung cancer is first suspected, keeping predictive biomarker testing in the front of the mind should drive the development of practices and procedures that conserve tissue appropriately to support molecular characterization and treatment selection.", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Keith M.", "last_name": "Kerr", "name": null }, { "creator_type": "author", "first_name": "Lukas", "last_name": "Bubendorf", "name": null }, { "creator_type": "author", "first_name": "Fernando", "last_name": "Lopez-Rios", "name": null }, { "creator_type": "author", "first_name": "Farah", "last_name": "Khalil", "name": null }, { "creator_type": "author", "first_name": "Sinchita", "last_name": "Roy-Chowdhuri", "name": null }, { "creator_type": "author", "first_name": "Philippe", "last_name": "Joubert", "name": null }, { "creator_type": "author", "first_name": "Arndt", "last_name": "Hartmann", "name": null }, { "creator_type": "author", "first_name": "Elena", "last_name": "Guerini-Rocco", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null }, { "creator_type": "author", "first_name": "Paul", "last_name": "Hofman", "name": null }, { "creator_type": "author", "first_name": "Wendy A.", "last_name": "Cooper", "name": null }, { "creator_type": "author", "first_name": "Sanja", "last_name": "Dacic", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/his.15078" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "37957137" } }, "mesh": [ { "descriptor": "Biomarkers, Tumor", "descriptor_ui": "D014408", "major_topic": false }, { "descriptor": "Carcinoma, Non-Small-Cell Lung", "descriptor_ui": "D002289", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Lung Neoplasms", "descriptor_ui": "D008175", "major_topic": true }, { "descriptor": "Molecular Targeted Therapy", "descriptor_ui": "D058990", "major_topic": false }, { "descriptor": "Pathologists", "descriptor_ui": "D000072142", "major_topic": false } ], "publication": { "conference_name": null, "date": "2023 Nov 13", "date_precision": "day", "issue": "", "normalized_date": "2023-11-13", "pages": "", "proceedings_title": null, "publisher": "", "title": "Histopathology", "volume": "", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Optimizing tissue stewardship in non-small cell lung cancer to support molecular characterization and treatment selection: statement from a working group of thoracic pathologists.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Hyponatremia and salt wasting is a common occurance in patients with HIV/AIDS, however, the understanding of its contributing factors is limited. HIV viral protein R (Vpr) contributes to HIV-associated nephropathy. To investigate the effects of Vpr on the expression level of the Slc12a3 gene, encoding the Na-Cl cotransporter, which is responsible for sodium reabsorption in distal nephron segments, we performed single-nucleus RNA sequencing of kidney cortices from three wild-type (WT) and three Vpr-transgenic (Vpr Tg) mice. The results showed that the percentage of distal convoluted tubule (DCT) cells was significantly lower in Vpr Tg mice compared with WT mice (P < 0.05), and that in Vpr Tg mice, Slc12a3 expression was not different in DCT cell cluster. The Pvalb(+) DCT1 subcluster had fewer cells in Vpr Tg mice compared with WT (P < 0.01). Immunohistochemistry demonstrated fewer Slc12a3(+) Pvalb(+) DCT1 segments in Vpr Tg mice. Differential gene expression analysis comparing Vpr Tg and WT in the DCT cluster showed Ier3, an inhibitor of apoptosis, to be the most downregulated gene. These observations demonstrate that the salt-wasting effect of Vpr in Vpr Tg mice is mediated by loss of Slc12a3(+) Pvalb(+) DCT1 segments via apoptosis dysregulation.", "classifications": [ { "id": "Okamoto", "label": "Group Okamoto", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Khun Zaw", "last_name": "Latt", "name": null }, { "creator_type": "author", "first_name": "Teruhiko", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Shashi", "last_name": "Shrivastav", "name": null }, { "creator_type": "author", "first_name": "Amin", "last_name": "Abedini", "name": null }, { "creator_type": "author", "first_name": "Jeff M.", "last_name": "Reece", "name": null }, { "creator_type": "author", "first_name": "Zeguo", "last_name": "Sun", "name": null }, { "creator_type": "author", "first_name": "Hewang", "last_name": "Lee", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Okamoto", "name": null }, { "creator_type": "author", "first_name": "Pradeep", "last_name": "Dagur", "name": null }, { "creator_type": "author", "first_name": "Jurgen", "last_name": "Heymann", "name": null }, { "creator_type": "author", "first_name": "Yongmei", "last_name": "Zhao", "name": null }, { "creator_type": "author", "first_name": "Joon-Yong", "last_name": "Chung", "name": null }, { "creator_type": "author", "first_name": "Stephen", "last_name": "Hewitt", "name": null }, { "creator_type": "author", "first_name": "Pedro A.", "last_name": "Jose", "name": null }, { "creator_type": "author", "first_name": "Kyung", "last_name": "Lee", "name": null }, { "creator_type": "author", "first_name": "John Cijiang", "last_name": "He", "name": null }, { "creator_type": "author", "first_name": "Cheryl A.", "last_name": "Winkler", "name": null }, { "creator_type": "author", "first_name": "Mark A.", "last_name": "Knepper", "name": null }, { "creator_type": "author", "first_name": "Tomoshige", "last_name": "Kino", "name": null }, { "creator_type": "author", "first_name": "Avi Z.", "last_name": "Rosenberg", "name": null }, { "creator_type": "author", "first_name": "Katalin", "last_name": "Susztak", "name": null }, { "creator_type": "author", "first_name": "Jeffrey B.", "last_name": "Kopp", "name": null } ], "identifiers": { "doi": { "normalized": "10.1101/2023.02.02.526686" }, "pmcid": { "normalized": null }, "pmid": { "normalized": null } }, "mesh": [], "publication": { "conference_name": null, "date": "2023 Nov 13", "date_precision": "day", "issue": null, "normalized_date": "2023-11-13", "pages": null, "proceedings_title": null, "publisher": null, "title": null, "volume": null, "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "HIV viral protein R induces loss of DCT1-type renal tubules.", "url": "", "zotero": { "item_type": "preprint" } }, { "abstract": "", "classifications": [ { "id": "Higaki", "label": "Group Higaki", "parent": "Ueda", "type": "group" }, { "id": "Ueda", "label": "Team Ueda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Keiji", "last_name": "Nakajima", "name": null }, { "creator_type": "author", "first_name": "Takumi", "last_name": "Higaki", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Ueda", "name": null }, { "creator_type": "author", "first_name": "Masahiko", "last_name": "Inami", "name": null } ], "identifiers": { "doi": { "normalized": "10.1093/pcp/pcad144" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "37952100" } }, "mesh": [ { "descriptor": "Biology", "descriptor_ui": "D001695", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Plants", "descriptor_ui": "D010944", "major_topic": true } ], "publication": { "conference_name": null, "date": "2023 Nov 10", "date_precision": "day", "issue": "", "normalized_date": "2023-11-10", "pages": "pcad144", "proceedings_title": null, "publisher": "", "title": "Plant & cell physiology", "volume": "", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Gaining new insights in plant biology through human-machine collaboration.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "In autosomal dominant polycystic kidney disease (ADPKD), renal cyst lesions predominantly arise from collecting ducts (CDs). However, relevant CD cyst models using human cells are lacking. Although previous reports have generated in vitro renal tubule cyst models from human induced pluripotent stem cells (hiPSCs), therapeutic drug candidates for ADPKD have not been identified. Here, by establishing expansion cultures of hiPSC-derived ureteric bud tip cells, an embryonic precursor that gives rise to CDs, we succeed in advancing the developmental stage of CD organoids and show that all CD organoids derived from PKD1(-/-) hiPSCs spontaneously develop multiple cysts, clarifying the initiation mechanisms of cystogenesis. Moreover, we identify retinoic acid receptor (RAR) agonists as candidate drugs that suppress in vitro cystogenesis and confirm the therapeutic effects on an ADPKD mouse model in vivo. Therefore, our in vitro CD cyst model contributes to understanding disease mechanisms and drug discovery for ADPKD.", "classifications": [ { "id": "JPMJCR2123", "label": "JPMJCR2123", "researcher": "Shinya Kuroda", "type": "grant" }, { "id": "Kuroda", "label": "Group Kuroda", "parent": "Kuroda", "type": "group" }, { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Shin-Ichi", "last_name": "Mae", "name": null }, { "creator_type": "author", "first_name": "Fumihiko", "last_name": "Hattanda", "name": null }, { "creator_type": "author", "first_name": "Hiroyoshi", "last_name": "Morita", "name": null }, { "creator_type": "author", "first_name": "Aya", "last_name": "Nozaki", "name": null }, { "creator_type": "author", "first_name": "Naoko", "last_name": "Katagiri", "name": null }, { "creator_type": "author", "first_name": "Hanako", "last_name": "Ogawa", "name": null }, { "creator_type": "author", "first_name": "Kaori", "last_name": "Teranaka", "name": null }, { "creator_type": "author", "first_name": "Yu", "last_name": "Nishimura", "name": null }, { "creator_type": "author", "first_name": "Aoi", "last_name": "Kudoh", "name": null }, { "creator_type": "author", "first_name": "Sanae", "last_name": "Yamanaka", "name": null }, { "creator_type": "author", "first_name": "Kyoko", "last_name": "Matsuse", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Ryosaka", "name": null }, { "creator_type": "author", "first_name": "Akira", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Saori", "last_name": "Nishio", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Osafune", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.celrep.2023.113431" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "38039961" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cysts", "descriptor_ui": "D003560", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Induced Pluripotent Stem Cells", "descriptor_ui": "D057026", "major_topic": true }, { "descriptor": "Kidney", "descriptor_ui": "D007668", "major_topic": false }, { "descriptor": "Kidney Neoplasms", "descriptor_ui": "D007680", "major_topic": true }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Organoids", "descriptor_ui": "D009940", "major_topic": false }, { "descriptor": "Polycystic Kidney, Autosomal Dominant", "descriptor_ui": "D016891", "major_topic": true }, { "descriptor": "TRPP Cation Channels", "descriptor_ui": "D050396", "major_topic": false } ], "publication": { "conference_name": null, "date": "2023 Nov 10", "date_precision": "day", "issue": "", "normalized_date": "2023-11-10", "pages": "113431", "proceedings_title": null, "publisher": "", "title": "Cell reports", "volume": "", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Human iPSC-derived renal collecting duct organoid model cystogenesis in ADPKD.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Salivary gland-type tumor (SGT) of the lung, which arises from the bronchial glands of the tracheobronchial tree, was first recognized in the 1950s. SGT represents less than 1% of all lung tumors and is generally reported to have a good prognosis. Mucoepidermoid carcinoma (MEC) and adenoid cystic carcinoma (ACC) are the two most common subtypes, comprising more than 90% of all SGTs. The reported 5-year survival rate of patients with SGT is 63.4%. Because this type of tumor develops in major bronchi, patients with SGT commonly present with symptoms of bronchial obstruction, including dyspnea, shortness of breath, wheezing, and coughing; thus, the tumor is usually identified at an early stage. Most patients are treated by lobectomy and pneumonectomy, but bronchoplasty or tracheoplasty is often needed to preserve respiratory function. Lymphadenectomy in the surgical resection of SGT is recommended, given that clinical benefit from lymphadenectomy has been reported in patients with MEC. For advanced tumors, appropriate therapy should be considered according to the subtype because of the varying clinicopathologic features. MEC, but not ACC, is less likely to be treated with radiation therapy because of its low response rate. Although previous researchers have learned much from studying SGT over the years, the diagnosis and treatment of SGT remains a complex and challenging problem for thoracic surgeons. In this article, we review the diagnosis, prognosis, and treatment (surgery, chemotherapy, and radiotherapy) of SGT, mainly focusing on MEC and ACC. We also summarize reports of adjuvant and definitive radiation therapy for ACC in the literature.", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Shinkichi", "last_name": "Takamori", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Osoegawa", "name": null }, { "creator_type": "author", "first_name": "Keiju", "last_name": "Aokage", "name": null }, { "creator_type": "author", "first_name": "Hiroshige", "last_name": "Yoshioka", "name": null }, { "creator_type": "author", "first_name": "Tomohiro", "last_name": "Miyoshi", "name": null }, { "creator_type": "author", "first_name": "Takahiro", "last_name": "Mimae", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Endo", "name": null }, { "creator_type": "author", "first_name": "Aritoshi", "last_name": "Hattori", "name": null }, { "creator_type": "author", "first_name": "Masaya", "last_name": "Yotsukura", "name": null }, { "creator_type": "author", "first_name": "Tetsuya", "last_name": "Isaka", "name": null }, { "creator_type": "author", "first_name": "Mitsuhiro", "last_name": "Isaka", "name": null }, { "creator_type": "author", "first_name": "Tomohiro", "last_name": "Maniwa", "name": null }, { "creator_type": "author", "first_name": "Ryu", "last_name": "Nakajima", "name": null }, { "creator_type": "author", "first_name": "Shun-Ichi", "last_name": "Watanabe", "name": null } ], "identifiers": { "doi": { "normalized": "10.1093/jjco/hyad154" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "37952098" } }, "mesh": [ { "descriptor": "Carcinoma, Adenoid Cystic", "descriptor_ui": "D003528", "major_topic": true }, { "descriptor": "Carcinoma, Mucoepidermoid", "descriptor_ui": "D018277", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Lung", "descriptor_ui": "D008168", "major_topic": false }, { "descriptor": "Lung Neoplasms", "descriptor_ui": "D008175", "major_topic": true }, { "descriptor": "Salivary Gland Neoplasms", "descriptor_ui": "D012468", "major_topic": true }, { "descriptor": "Salivary Glands", "descriptor_ui": "D012469", "major_topic": false } ], "publication": { "conference_name": null, "date": "2023 Nov 10", "date_precision": "day", "issue": "", "normalized_date": "2023-11-10", "pages": "hyad154", "proceedings_title": null, "publisher": "", "title": "Japanese journal of clinical oncology", "volume": "", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Rare but clinically important salivary gland-type tumor of the lung: A review.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Currently, lung cancer is treated by the highest number of therapeutic options and the benefits are based on multiple large-scale sequencing studies, translational research and new drug development, which has promoted our understanding of the molecular pathology of lung cancer. According to the driver alterations, different characteristics have been revealed, such as differences in ethnic prevalence, median age and alteration patterns. Consequently, beyond traditional chemoradiotherapy, molecular-targeted therapy and treatment with immune check-point inhibitors (ICI) also became available major therapeutic options. Interestingly, clinical results suggest that the recently established therapies target distinct lung cancer proportions, particularly between the EGFR/ALK and PD-1/PD-L1-positive subsets, e.g. the kinase inhibitors target driver mutation-positive tumours, whereas driver mutation-negative tumours respond to ICI treatment. These therapeutic efficacy-related differences might be explained by the molecular pathogenesis of lung cancer. Addictive driver mutations promote tumour formation with powerful transformation performance, resulting in a low tumour mutation burden, reduced immune surveillance, and subsequent poor response to ICIs. In contrast, regular tobacco smoke exposure repeatedly injures the proximal airway epithelium, leading to accumulated genetic alterations. In the latter pathway, overgrowth due to alteration and immunological exclusion against neoantigens is initially balanced. However, tumours could be generated from certain clones that outcompete immunological exclusion and outgrow the others. Consequently, this cancer type responds to immune check-point treatment. These pathogenic differences are explained well by the two-compartment model, focusing upon the anatomical and functional composition of distinct cellular components between the terminal respiratory unit and the air-conducting system.", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/his.15080" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "37936491" } }, "mesh": [ { "descriptor": "B7-H1 Antigen", "descriptor_ui": "D060890", "major_topic": false }, { "descriptor": "Carcinoma", "descriptor_ui": "D002277", "major_topic": true }, { "descriptor": "Carcinoma, Non-Small-Cell Lung", "descriptor_ui": "D002289", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Lung Neoplasms", "descriptor_ui": "D008175", "major_topic": true }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": false }, { "descriptor": "Pathology, Molecular", "descriptor_ui": "D057089", "major_topic": false } ], "publication": { "conference_name": null, "date": "2023 Nov 7", "date_precision": "day", "issue": "", "normalized_date": "2023-11-07", "pages": "", "proceedings_title": null, "publisher": "", "title": "Histopathology", "volume": "", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Molecular pathology of non-small cell carcinoma.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: Complex biological systems are described as a multitude of cell-cell interactions (CCIs). Recent single-cell RNA-sequencing studies focus on CCIs based on ligand-receptor (L-R) gene co-expression but the analytical methods are not appropriate to detect many-to-many CCIs. RESULTS: In this work, we propose scTensor, a novel method for extracting representative triadic relationships (or hypergraphs), which include ligand-expression, receptor-expression, and related L-R pairs. CONCLUSIONS: Through extensive studies with simulated and empirical datasets, we have shown that scTensor can detect some hypergraphs that cannot be detected using conventional CCI detection methods, especially when they include many-to-many relationships. scTensor is implemented as a freely available R/Bioconductor package.", "classifications": [ { "id": "JPMJCR1926", "label": "JPMJCR1926", "researcher": "Hironobu Fujiwara", "type": "grant" }, { "id": "Fujiwara", "label": "Group Fujiwara", "parent": "Fujiwara", "type": "group" }, { "id": "Nikaido", "label": "Group Nikaido", "parent": "Fujiwara", "type": "group" }, { "id": "Fujiwara", "label": "Team Fujiwara", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Koki", "last_name": "Tsuyuzaki", "name": null }, { "creator_type": "author", "first_name": "Manabu", "last_name": "Ishii", "name": null }, { "creator_type": "author", "first_name": "Itoshi", "last_name": "Nikaido", "name": null } ], "identifiers": { "doi": { "normalized": "10.1186/s12859-023-05490-y" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "37936079" } }, "mesh": [ { "descriptor": "Gene Expression", "descriptor_ui": "D015870", "major_topic": false }, { "descriptor": "Ligands", "descriptor_ui": "D008024", "major_topic": false }, { "descriptor": "RNA", "descriptor_ui": "D012313", "major_topic": true }, { "descriptor": "Sequence Analysis, RNA", "descriptor_ui": "D017423", "major_topic": false }, { "descriptor": "Software", "descriptor_ui": "D012984", "major_topic": true } ], "publication": { "conference_name": null, "date": "2023 Nov 7", "date_precision": "day", "issue": "1", "normalized_date": "2023-11-07", "pages": "420", "proceedings_title": null, "publisher": "", "title": "BMC bioinformatics", "volume": "24", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Sctensor detects many-to-many cell-cell interactions from single cell RNA-sequencing data.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Each tissue has a dominant set of functional proteins required to mediate tissue-specific functions. Epigenetic modifications, transcription, and translational efficiency control tissue-dominant protein production. However, the coordination of these regulatory mechanisms to achieve such tissue-specific protein production remains unclear. Here, we analyzed the DNA methylome, transcriptome, and proteome in mouse liver and skeletal muscle. We found that DNA hypomethylation at promoter regions is globally associated with liver-dominant or skeletal muscle-dominant functional protein production within each tissue, as well as with genes encoding proteins involved in ubiquitous functions in both tissues. Thus, genes encoding liver-dominant proteins, such as those involved in glycolysis or gluconeogenesis, the urea cycle, complement and coagulation systems, enzymes of tryptophan metabolism, and cytochrome P450-related metabolism, were hypomethylated in the liver, whereas those encoding-skeletal muscle-dominant proteins, such as those involved in sarcomere organization, were hypomethylated in the skeletal muscle. Thus, DNA hypomethylation characterizes genes encoding tissue-dominant functional proteins.", "classifications": [ { "id": "JPMJCR2123", "label": "JPMJCR2123", "researcher": "Shinya Kuroda", "type": "grant" }, { "id": "Kuroda", "label": "Group Kuroda", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Hideki", "last_name": "Maehara", "name": null }, { "creator_type": "author", "first_name": "Toshiya", "last_name": "Kokaji", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Hatano", "name": null }, { "creator_type": "author", "first_name": "Yutaka", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Masaki", "last_name": "Matsumoto", "name": null }, { "creator_type": "author", "first_name": "Keiichi I.", "last_name": "Nakayama", "name": null }, { "creator_type": "author", "first_name": "Riku", "last_name": "Egami", "name": null }, { "creator_type": "author", "first_name": "Takaho", "last_name": "Tsuchiya", "name": null }, { "creator_type": "author", "first_name": "Haruka", "last_name": "Ozaki", "name": null }, { "creator_type": "author", "first_name": "Keigo", "last_name": "Morita", "name": null }, { "creator_type": "author", "first_name": "Masaki", "last_name": "Shirai", "name": null }, { "creator_type": "author", "first_name": "Dongzi", "last_name": "Li", "name": null }, { "creator_type": "author", "first_name": "Akira", "last_name": "Terakawa", "name": null }, { "creator_type": "author", "first_name": "Saori", "last_name": "Uematsu", "name": null }, { "creator_type": "author", "first_name": "Ken-Ichi", "last_name": "Hironaka", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Ohno", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Kubota", "name": null }, { "creator_type": "author", "first_name": "Hiromitsu", "last_name": "Araki", "name": null }, { "creator_type": "author", "first_name": "Fumihito", "last_name": "Miura", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Kuroda", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41598-023-46393-5" }, "pmcid": { "normalized": "PMC10625943" }, "pmid": { "normalized": "37926704" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "DNA", "descriptor_ui": "D004247", "major_topic": false }, { "descriptor": "DNA Methylation", "descriptor_ui": "D019175", "major_topic": true }, { "descriptor": "Epigenesis, Genetic", "descriptor_ui": "D044127", "major_topic": false }, { "descriptor": "Liver", "descriptor_ui": "D008099", "major_topic": true }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Muscle Proteins", "descriptor_ui": "D009124", "major_topic": false }, { "descriptor": "Muscle, Skeletal", "descriptor_ui": "D018482", "major_topic": false } ], "publication": { "conference_name": null, "date": "2023 Nov 5", "date_precision": "day", "issue": "1", "normalized_date": "2023-11-05", "pages": "19118", "proceedings_title": null, "publisher": "", "title": "Scientific reports", "volume": "13", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "DNA hypomethylation characterizes genes encoding tissue-dominant functional proteins in liver and skeletal muscle.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: Heated tobacco products (HTPs) have gained global popularity, but their health risks remain unclear. Therefore, the current study aimed to identify plasma metabolites associated with smoking and HTP use in a large Japanese population to improve health risk assessment. METHODS: Metabolomics data from 9,922 baseline participants of the Tsuruoka Metabolomics Cohort Study (TMCS) were analyzed to determine the association between smoking habits and plasma metabolites. Moreover, alterations in smoking-related metabolites among HTP users were examined based on data obtained from 3,334 participants involved from April 2018 to June 2019 in a follow-up survey. RESULTS: Our study revealed that cigarette smokers had metabolomics profiles distinct from never smokers, with 22 polar metabolites identified as candidate biomarkers for smoking. These biomarker profiles of HTP users were closer to those of cigarette smokers than those of never smokers. The concentration of glutamate was higher in cigarette smokers, and biomarkers involved in glutamate metabolism were also associated with cigarette smoking and HTP use. Network pathway analysis showed that smoking was associated with the glutamate pathway, which could lead to endothelial dysfunction and atherosclerosis of the vessels. CONCLUSIONS: Our study showed that the glutamate pathway is affected by habitual smoking. These changes in the glutamate pathway may partly explain the mechanism by which cigarette smoking causes cardiovascular disease. HTP use was also associated with glutamate metabolism, indicating that HTP use may contribute to the development of cardiovascular disease through mechanisms similar to those in cigarette use.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Sei", "last_name": "Harada", "name": null }, { "creator_type": "author", "first_name": "Hideki", "last_name": "Ohmomo", "name": null }, { "creator_type": "author", "first_name": "Minako", "last_name": "Matsumoto", "name": null }, { "creator_type": "author", "first_name": "Mizuki", "last_name": "Sata", "name": null }, { "creator_type": "author", "first_name": "Miho", "last_name": "Iida", "name": null }, { "creator_type": "author", "first_name": "Aya", "last_name": "Hirata", "name": null }, { "creator_type": "author", "first_name": "Naoko", "last_name": "Miyagawa", "name": null }, { "creator_type": "author", "first_name": "Kazuyo", "last_name": "Kuwabara", "name": null }, { "creator_type": "author", "first_name": "Suzuka", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Ryota", "last_name": "Toki", "name": null }, { "creator_type": "author", "first_name": "Shun", "last_name": "Edagawa", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Sugiyama", "name": null }, { "creator_type": "author", "first_name": "Asako", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Akiyoshi", "last_name": "Hirayama", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Sugimoto", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Masaru", "last_name": "Tomita", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Shimizu", "name": null }, { "creator_type": "author", "first_name": "Tomonori", "last_name": "Okamura", "name": null }, { "creator_type": "author", "first_name": "Toru", "last_name": "Takebayashi", "name": null } ], "identifiers": { "doi": { "normalized": "10.2188/jea.je20230170" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "37926518" } }, "mesh": [ { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Biomarkers", "descriptor_ui": "D015415", "major_topic": true }, { "descriptor": "Cigarette Smoking", "descriptor_ui": "D000073865", "major_topic": true }, { "descriptor": "Cohort Studies", "descriptor_ui": "D015331", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Hot Temperature", "descriptor_ui": "D006358", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Japan", "descriptor_ui": "D007564", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Metabolomics", "descriptor_ui": "D055432", "major_topic": true }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Smokers", "descriptor_ui": "D000074285", "major_topic": true }, { "descriptor": "Tobacco Products", "descriptor_ui": "D062789", "major_topic": true } ], "publication": { "conference_name": null, "date": "2023 Nov 4", "date_precision": "day", "issue": "", "normalized_date": "2023-11-04", "pages": "", "proceedings_title": null, "publisher": "", "title": "Journal of epidemiology", "volume": "", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Metabolomics profiles alterations in cigarette smokers and heated tobacco product users.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "", "classifications": [ { "id": "Hamamoto", "label": "Group Hamamoto", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Masayuki", "last_name": "Shirasawa", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Kouya", "last_name": "Shiraishi", "name": null }, { "creator_type": "author", "first_name": "Naoko", "last_name": "Goto", "name": null }, { "creator_type": "author", "first_name": "Shigehiro", "last_name": "Yagishita", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Imabayashi", "name": null }, { "creator_type": "author", "first_name": "Yuji", "last_name": "Matsumoto", "name": null }, { "creator_type": "author", "first_name": "Ken", "last_name": "Masuda", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Shinno", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Okuma", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Goto", "name": null }, { "creator_type": "author", "first_name": "Hidehito", "last_name": "Horinouchi", "name": null }, { "creator_type": "author", "first_name": "Masaya", "last_name": "Yotsukura", "name": null }, { "creator_type": "author", "first_name": "Yukihiro", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Kazuo", "last_name": "Nakagawa", "name": null }, { "creator_type": "author", "first_name": "Katsuhiko", "last_name": "Naoki", "name": null }, { "creator_type": "author", "first_name": "Takaaki", "last_name": "Tsuchida", "name": null }, { "creator_type": "author", "first_name": "Ryuji", "last_name": "Hamamoto", "name": null }, { "creator_type": "author", "first_name": "Noboru", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Noriko", "last_name": "Motoi", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Kohno", "name": null }, { "creator_type": "author", "first_name": "Shun-Ichi", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Yuichiro", "last_name": "Ohe", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41416-023-02481-x" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "37923915" } }, "mesh": [], "publication": { "conference_name": null, "date": "2023 Nov 3", "date_precision": "day", "issue": "", "normalized_date": "2023-11-03", "pages": "", "proceedings_title": null, "publisher": "", "title": "British journal of cancer", "volume": "", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Correction: Tumor microenvironment-mediated immune profiles and efficacy of anti-PD-L1 antibody plus chemotherapy stratified by DLL3 expression in small-cell lung cancer.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Acute leukemia cells require bone marrow microenvironments, termed niches, which provide leukemic cells with niche factors that are essential for leukemic cell survival and/or proliferation. However, it remains unclear how the dynamics of the leukemic cell-niche interaction are regulated. Using a genome-wide CRISPR screen, we discovered that canonical BRG1/BRM-associated factor (cBAF), a variant of the switch/sucrose non-fermenting chromatin remodeling complex, regulates migratory response of human T-cell acute lymphoblastic leukemia (T-ALL) cells to a niche factor CXCL12. Mechanistically, cBAF maintains chromatin accessibility and allows RUNX1 to bind to CXCR4 enhancer regions. cBAF inhibition evicts RUNX1 from the genome, resulting in CXCR4 downregulation and impaired migration activity. In addition, cBAF maintains chromatin accessibility preferentially at RUNX1 binding sites, ensuring RUNX1 binding at these sites, and is required for expression of RUNX1-regulated genes, such as CDK6; therefore, cBAF inhibition negatively impacts cell proliferation and profoundly induces apoptosis. This anticancer effect was also confirmed using T-ALL xenograft models, suggesting cBAF as a promising therapeutic target. Thus, we provide novel evidence that cBAF regulates the RUNX1-driven leukemic program and governs migration activity toward CXCL12 and cell-autonomous growth in human T-ALL.", "classifications": [ { "id": "Yusa", "label": "Group Yusa", "parent": "Eiraku", "type": "group" }, { "id": "Eiraku", "label": "Team Eiraku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Kazunari", "last_name": "Aoki", "name": null }, { "creator_type": "author", "first_name": "Mizuki", "last_name": "Hyuga", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Tarumoto", "name": null }, { "creator_type": "author", "first_name": "Gohei", "last_name": "Nishibuchi", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Ueda", "name": null }, { "creator_type": "author", "first_name": "Yotaro", "last_name": "Ochi", "name": null }, { "creator_type": "author", "first_name": "Seiichi", "last_name": "Sugino", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Mikami", "name": null }, { "creator_type": "author", "first_name": "Hirokazu", "last_name": "Kobushi", "name": null }, { "creator_type": "author", "first_name": "Itaru", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Koshi", "last_name": "Akahane", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Inukai", "name": null }, { "creator_type": "author", "first_name": "Akifumi", "last_name": "Takaori-Kondo", "name": null }, { "creator_type": "author", "first_name": "Junko", "last_name": "Takita", "name": null }, { "creator_type": "author", "first_name": "Seishi", "last_name": "Ogawa", "name": null }, { "creator_type": "author", "first_name": "Kosuke", "last_name": "Yusa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1182/blood.2023020857" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "37922452" } }, "mesh": [ { "descriptor": "Bone Marrow", "descriptor_ui": "D001853", "major_topic": false }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Chromatin", "descriptor_ui": "D002843", "major_topic": false }, { "descriptor": "Core Binding Factor Alpha 2 Subunit", "descriptor_ui": "D050676", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Precursor T-Cell Lymphoblastic Leukemia-Lymphoma", "descriptor_ui": "D054218", "major_topic": true }, { "descriptor": "T-Lymphocytes", "descriptor_ui": "D013601", "major_topic": false }, { "descriptor": "Tumor Microenvironment", "descriptor_ui": "D059016", "major_topic": false } ], "publication": { "conference_name": null, "date": "2023 Nov 3", "date_precision": "day", "issue": "", "normalized_date": "2023-11-03", "pages": "blood.2023020857", "proceedings_title": null, "publisher": "", "title": "Blood", "volume": "", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Canonical BAF complex regulates the oncogenic program in human T-cell acute lymphoblastic leukemia.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "One hallmark of some autoimmune diseases is the variability of symptoms among individuals. Organs affected by the disease differ between patients, posing a challenge in diagnosing the affected organs. Although numerous studies have investigated the correlation between T cell antigen receptor (TCR) repertoires and the development of infectious and immune diseases, the correlation between TCR repertoires and variations in disease symptoms among individuals remains unclear. This study aimed to investigate the correlation of TCRalpha and beta repertoires in blood T cells with the extent of autoimmune signs that varies among individuals. We sequenced TCRalpha and beta of CD4(+) CD44(high) CD62L(low) T cells in the blood and stomachs of mice deficient in autoimmune regulator (Aire) (AIRE KO), a mouse model of human autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy. Data analysis revealed that the degree of similarity in TCR sequences between the blood and stomach varied among individual AIRE KO mice and reflected the extent of T cell infiltration in the stomach. We identified a set of TCR sequences whose frequencies in blood might correlate with extent of the stomach manifestations. Our results propose a potential of using TCR repertoires not only for diagnosing disease development but also for diagnosing affected organs in autoimmune diseases.", "classifications": [ { "id": "Kobayashi", "label": "Group Kobayashi", "parent": "Wakamoto", "type": "group" }, { "id": "Wakamoto", "label": "Team Wakamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Ishikawa", "name": null }, { "creator_type": "author", "first_name": "Kenta", "last_name": "Horie", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Takakura", "name": null }, { "creator_type": "author", "first_name": "Houko", "last_name": "Ohki", "name": null }, { "creator_type": "author", "first_name": "Yuya", "last_name": "Maruyama", "name": null }, { "creator_type": "author", "first_name": "Mio", "last_name": "Hayama", "name": null }, { "creator_type": "author", "first_name": "Maki", "last_name": "Miyauchi", "name": null }, { "creator_type": "author", "first_name": "Takahisa", "last_name": "Miyao", "name": null }, { "creator_type": "author", "first_name": "Naho", "last_name": "Hagiwara", "name": null }, { "creator_type": "author", "first_name": "Tetsuya J.", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Nobuko", "last_name": "Akiyama", "name": null }, { "creator_type": "author", "first_name": "Taishin", "last_name": "Akiyama", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/gtc.13079" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "37909727" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Autoimmune Diseases", "descriptor_ui": "D001327", "major_topic": true }, { "descriptor": "CD4-Positive T-Lymphocytes", "descriptor_ui": "D015496", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Polyendocrinopathies, Autoimmune", "descriptor_ui": "D016884", "major_topic": true }, { "descriptor": "Receptors, Antigen, T-Cell", "descriptor_ui": "D011948", "major_topic": false } ], "publication": { "conference_name": null, "date": "2023 Nov 1", "date_precision": "day", "issue": "", "normalized_date": "2023-11-01", "pages": "", "proceedings_title": null, "publisher": "", "title": "Genes to cells : devoted to molecular & cellular mechanisms", "volume": "", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "T-cell receptor repertoire analysis of CD4-positive T cells from blood and an affected organ in an autoimmune mouse model.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "During early development, neurons in the brain often form excess synaptic connections. Later, they strengthen some connections while eliminating others to build functional neuronal circuits. In the olfactory bulb, a mitral cell initially extends multiple dendrites to multiple glomeruli but eventually forms a single primary dendrite through the activity-dependent dendrite pruning process. Recent studies have reported that microglia facilitate synapse pruning during the circuit remodeling in some systems. It has remained unclear whether microglia are involved in the activity-dependent dendrite pruning in the developing brains. Here, we examined whether microglia are required for the developmental dendrite pruning of mitral cells in mice. To deplete microglia in the fetal brain, we treated mice with a CSF1R inhibitor, PLX5622, from pregnancy. Microglia were reduced by >90% in mice treated with PLX5622. However, dendrite pruning of mitral cells was not significantly affected. Moreover, we found no significant differences in the number, density, and size of excitatory synapses formed in mitral cell dendrites. We also found no evidence for the role of microglia in the activity-dependent dendrite remodeling of layer 4 neurons in the barrel cortex. In contrast, the density of excitatory synapses (dendritic spines) in granule cells in the olfactory bulb was significantly increased in mice treated with PLX5622 at P6, suggesting a role for the regulation of dendritic spines. Our results indicate that microglia do not play a critical role in activity-dependent dendrite pruning at the neurite level during early postnatal development in mice.Significance StatementSynapse elimination is essential for activity-dependent circuit remodeling in the developing brains of mammals. Recent studies suggested that microglia play a critical role in the synapse elimination. This study found that microglia are dispensable for the activity-dependent dendrite pruning in developing mitral cells and layer 4 neurons in the barrel cortex. Thus, microglia are not critical for activity-dependent dendrite pruning at the neurite level during normal developmental process.", "classifications": [ { "id": "JPMJCR2021", "label": "JPMJCR2021", "researcher": "Hideki Enomoto", "type": "grant" }, { "id": "Enomoto", "label": "Group Enomoto", "parent": "Enomoto", "type": "group" }, { "id": "Imai", "label": "Group Imai", "parent": "Enomoto", "type": "group" }, { "id": "Enomoto", "label": "Team Enomoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Tetsushi", "last_name": "Niiyama", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Fujimoto", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Imai", "name": null } ], "identifiers": { "doi": { "normalized": "10.1523/eneuro.0323-23.2023" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "37890992" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Dendrites", "descriptor_ui": "D003712", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Microglia", "descriptor_ui": "D017628", "major_topic": true }, { "descriptor": "Neuronal Plasticity", "descriptor_ui": "D009473", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": true }, { "descriptor": "Organic Chemicals", "descriptor_ui": "D009930", "major_topic": false }, { "descriptor": "Synapses", "descriptor_ui": "D013569", "major_topic": false } ], "publication": { "conference_name": null, "date": "2023 Oct 27", "date_precision": "day", "issue": "", "normalized_date": "2023-10-27", "pages": "ENEURO.0323-23.2023", "proceedings_title": null, "publisher": "", "title": "eNeuro", "volume": "", "year": 2023 }, "ssbd": { "database": [], "repository": [ "ssbd-repos-000326" ] }, "title": "Microglia are dispensable for developmental dendrite pruning of mitral cells in mice.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "", "classifications": [ { "id": "Hamamoto", "label": "Group Hamamoto", "parent": "Okamoto", "type": "group" }, { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Kouya", "last_name": "Shiraishi", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Yukihide", "last_name": "Momozawa", "name": null }, { "creator_type": "author", "first_name": "Yataro", "last_name": "Daigo", "name": null }, { "creator_type": "author", "first_name": "Syuzo", "last_name": "Kaneko", "name": null }, { "creator_type": "author", "first_name": "Takahisa", "last_name": "Kawaguchi", "name": null }, { "creator_type": "author", "first_name": "Hideo", "last_name": "Kunitoh", "name": null }, { "creator_type": "author", "first_name": "Shingo", "last_name": "Matsumoto", "name": null }, { "creator_type": "author", "first_name": "Hidehito", "last_name": "Horinouchi", "name": null }, { "creator_type": "author", "first_name": "Akiteru", "last_name": "Goto", "name": null }, { "creator_type": "author", "first_name": "Takayuki", "last_name": "Honda", "name": null }, { "creator_type": "author", "first_name": "Kimihiro", "last_name": "Shimizu", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Torasawa", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Takayanagi", "name": null }, { "creator_type": "author", "first_name": "Motonobu", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Akira", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Yuichiro", "last_name": "Ohe", "name": null }, { "creator_type": "author", "first_name": "Shun-Ichi", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Koichi", "last_name": "Goto", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Tsuboi", "name": null }, { "creator_type": "author", "first_name": "Katsuya", "last_name": "Tsuchihara", "name": null }, { "creator_type": "author", "first_name": "Sadaaki", "last_name": "Takata", "name": null }, { "creator_type": "author", "first_name": "Tomomi", "last_name": "Aoi", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Takano", "name": null }, { "creator_type": "author", "first_name": "Masashi", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Yohei", "last_name": "Miyagi", "name": null }, { "creator_type": "author", "first_name": "Kazumi", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Daichi", "last_name": "Maeda", "name": null }, { "creator_type": "author", "first_name": "Takumi", "last_name": "Yamaura", "name": null }, { "creator_type": "author", "first_name": "Maiko", "last_name": "Matsuda", "name": null }, { "creator_type": "author", "first_name": "Yoko", "last_name": "Shimada", "name": null }, { "creator_type": "author", "first_name": "Takaaki", "last_name": "Mizuno", "name": null }, { "creator_type": "author", "first_name": "Hiromi", "last_name": "Sakamoto", "name": null }, { "creator_type": "author", "first_name": "Teruhiko", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Goto", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Taiki", "last_name": "Yamaji", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Sonobe", "name": null }, { "creator_type": "author", "first_name": "Shinichi", "last_name": "Toyooka", "name": null }, { "creator_type": "author", "first_name": "Kazue", "last_name": "Yoneda", "name": null }, { "creator_type": "author", "first_name": "Katsuhiro", "last_name": "Masago", "name": null }, { "creator_type": "author", "first_name": "Fumihiro", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Megumi", "last_name": "Hara", "name": null }, { "creator_type": "author", "first_name": "Nobuo", "last_name": "Fuse", "name": null }, { "creator_type": "author", "first_name": "Satoshi S.", "last_name": "Nishizuka", "name": null }, { "creator_type": "author", "first_name": "Noriko", "last_name": "Motoi", "name": null }, { "creator_type": "author", "first_name": "Norie", "last_name": "Sawada", "name": null }, { "creator_type": "author", "first_name": "Yuichiro", "last_name": "Nishida", "name": null }, { "creator_type": "author", "first_name": "Kazuki", "last_name": "Kumada", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Takeuchi", "name": null }, { "creator_type": "author", "first_name": "Kozo", "last_name": "Tanno", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null }, { "creator_type": "author", "first_name": "Kuniko", "last_name": "Sunami", "name": null }, { "creator_type": "author", "first_name": "Tomoyuki", "last_name": "Hishida", "name": null }, { "creator_type": "author", "first_name": "Yasunari", "last_name": "Miyazaki", "name": null }, { "creator_type": "author", "first_name": "Hidemi", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Mitsuhiro", "last_name": "Amemiya", "name": null }, { "creator_type": "author", "first_name": "Hirohiko", "last_name": "Totsuka", "name": null }, { "creator_type": "author", "first_name": "Haruhiko", "last_name": "Nakayama", "name": null }, { "creator_type": "author", "first_name": "Tomoyuki", "last_name": "Yokose", "name": null }, { "creator_type": "author", "first_name": "Kazuyoshi", "last_name": "Ishigaki", "name": null }, { "creator_type": "author", "first_name": "Toshiteru", "last_name": "Nagashima", "name": null }, { "creator_type": "author", "first_name": "Yoichi", "last_name": "Ohtaki", "name": null }, { "creator_type": "author", "first_name": "Kazuhiro", "last_name": "Imai", "name": null }, { "creator_type": "author", "first_name": "Ken", "last_name": "Takasawa", "name": null }, { "creator_type": "author", "first_name": "Yoshihiro", "last_name": "Minamiya", "name": null }, { "creator_type": "author", "first_name": "Kazuma", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Kenichi", "last_name": "Okubo", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Wakai", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Shimizu", "name": null }, { "creator_type": "author", "first_name": "Masayuki", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Motoki", "last_name": "Iwasaki", "name": null }, { "creator_type": "author", "first_name": "Koichi", "last_name": "Matsuda", "name": null }, { "creator_type": "author", "first_name": "Johji", "last_name": "Inazawa", "name": null }, { "creator_type": "author", "first_name": "Yuichi", "last_name": "Shiraishi", "name": null }, { "creator_type": "author", "first_name": "Hiroyoshi", "last_name": "Nishikawa", "name": null }, { "creator_type": "author", "first_name": "Yoshinori", "last_name": "Murakami", "name": null }, { "creator_type": "author", "first_name": "Michiaki", "last_name": "Kubo", "name": null }, { "creator_type": "author", "first_name": "Fumihiko", "last_name": "Matsuda", "name": null }, { "creator_type": "author", "first_name": "Yoichiro", "last_name": "Kamatani", "name": null }, { "creator_type": "author", "first_name": "Ryuji", "last_name": "Hamamoto", "name": null }, { "creator_type": "author", "first_name": "Keitaro", "last_name": "Matsuo", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Kohno", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/cac2.12498" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "37882647" } }, "mesh": [ { "descriptor": "Adenocarcinoma of Lung", "descriptor_ui": "D000077192", "major_topic": true }, { "descriptor": "Genome-Wide Association Study", "descriptor_ui": "D055106", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Lung Neoplasms", "descriptor_ui": "D008175", "major_topic": true }, { "descriptor": "Telomere", "descriptor_ui": "D016615", "major_topic": false }, { "descriptor": "Whole Genome Sequencing", "descriptor_ui": "D000073336", "major_topic": false } ], "publication": { "conference_name": null, "date": "2023 Oct 26", "date_precision": "day", "issue": "", "normalized_date": "2023-10-26", "pages": "", "proceedings_title": null, "publisher": "", "title": "Cancer communications (London, England)", "volume": "", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Identification of telomere maintenance gene variations related to lung adenocarcinoma risk by genome-wide association and whole genome sequencing analyses.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "For decades, the major focus of redox biology has been oxygen, the most abundant element on Earth. Molecular oxygen functions as the final electron acceptor in the mitochondrial respiratory chain, thus contributing to energy production in aerobic organisms. In addition, oxygen-derived reactive oxygen species that include hydrogen peroxide, oxygen and nitrogen free radicals, such as superoxide, hydroxyl radical, and nitric oxide radical, undergo a complicated sequence of electron transfer reactions with other biomolecules, which lead to their modified physiological functions and diverse biological and pathophysiological consequences (e.g. oxidative stress). What is now evident is that oxygen accounts for only a small number of redox reactions in organisms, and knowledge of the general landscape of biological redox reactions is still quite limited. This article discusses a new revision of redox biology, which is governed by redox-active sulfur-containing molecules - supersulfides. We define the term \"supersulfides\" as sulfur species with catenated sulfur atoms. Supersulfides were determined to be abundant in all organisms, but their redox biological properties have remained largely unexplored. In fact, the unique chemical properties of supersulfides permit them to be readily ionized or radicalized, thereby allowing supersulfides to actively participate in redox reactions and antioxidant responses in cells. Accumulating evidence has demonstrated that supersulfides are indispensable for fundamental biological processes such as energy production, nucleic acid metabolism, protein translation, and others. Moreover, manipulation of supersulfide levels was beneficial for pathogenesis of various diseases. Thus, supersulfide biology has opened a new era of disease control that includes potential applications to clinical diagnosis, prevention, and therapeutics of diseases.", "classifications": [ { "id": "JPMJCR2024", "label": "JPMJCR2024", "researcher": "Motohiro Nishida", "type": "grant" }, { "id": "Akaike", "label": "Group Akaike", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Group Nishida", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Uladzimir", "last_name": "Barayeu", "name": null }, { "creator_type": "author", "first_name": "Tomohiro", "last_name": "Sawa", "name": null }, { "creator_type": "author", "first_name": "Motohiro", "last_name": "Nishida", "name": null }, { "creator_type": "author", "first_name": "Fan-Yan", "last_name": "Wei", "name": null }, { "creator_type": "author", "first_name": "Hozumi", "last_name": "Motohashi", "name": null }, { "creator_type": "author", "first_name": "Takaaki", "last_name": "Akaike", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/bph.16271" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "37872133" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Oxidation-Reduction", "descriptor_ui": "D010084", "major_topic": false }, { "descriptor": "Sulfides", "descriptor_ui": "D013440", "major_topic": true }, { "descriptor": "Translational Research, Biomedical", "descriptor_ui": "D057170", "major_topic": true } ], "publication": { "conference_name": null, "date": "2023 Oct 23", "date_precision": "day", "issue": "", "normalized_date": "2023-10-23", "pages": "", "proceedings_title": null, "publisher": "", "title": "British journal of pharmacology", "volume": "", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Supersulfide biology and translational medicine for disease control.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Type 2 diabetes (T2D) is a progressive disorder denoted by hyperglycemia and impaired insulin secretion. Although a decrease in beta-cell function and mass is a well-known trigger for diabetes, the comprehensive mechanism is still unidentified. Here we carried out single-cell RNA sequencing (scRNA-seq) of pancreatic islets from prediabetic and diabetic db/db mice, an animal model of T2D. We discovered a diabetes-specific transcriptome landscape of endocrine and nonendocrine cell types with subpopulations of beta and alpha cells. We recognized a new prediabetic gene, Anxa10, that was induced by, and regulated Ca2+ influx from metabolic stresses. Anxa10-overexpressed beta cells displayed suppression of glucose-stimulated intracellular Ca2+ elevation and potassiuminduced insulin secretion. Pseudotime analysis of beta cells predicted this Ca2+-surge responder-cluster proceeded to mitochondria dysfunction and also endoplasmic reticulum stress. Other trajectories comprised dedifferentiation and transdifferentiation, emphasizing acinar-like cells in diabetic islets. Altogether, our data provides a new insight into Ca2+ allostasis and beta cell failure processes.", "classifications": [ { "id": "Miyamoto", "label": "Group Miyamoto", "parent": "Wakamoto", "type": "group" }, { "id": "Wakamoto", "label": "Team Wakamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Kaori", "last_name": "Motomura", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Matsuzaka", "name": null }, { "creator_type": "author", "first_name": "Shigeyuki", "last_name": "Shichino", "name": null }, { "creator_type": "author", "first_name": "Tatsuro", "last_name": "Ogawa", "name": null }, { "creator_type": "author", "first_name": "Hao", "last_name": "Pan", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Nakajima", "name": null }, { "creator_type": "author", "first_name": "Yasuhito", "last_name": "Asano", "name": null }, { "creator_type": "author", "first_name": "Toshitsugu", "last_name": "Okayama", "name": null }, { "creator_type": "author", "first_name": "Tomoyo", "last_name": "Takeuchi", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Ohno", "name": null }, { "creator_type": "author", "first_name": "Song-Iee", "last_name": "Han", "name": null }, { "creator_type": "author", "first_name": "Takafumi", "last_name": "Miyamoto", "name": null }, { "creator_type": "author", "first_name": "Yoshinori", "last_name": "Takeuchi", "name": null }, { "creator_type": "author", "first_name": "Motohiro", "last_name": "Sekiya", "name": null }, { "creator_type": "author", "first_name": "Hirohito", "last_name": "Sone", "name": null }, { "creator_type": "author", "first_name": "Naoya", "last_name": "Yahagi", "name": null }, { "creator_type": "author", "first_name": "Yoshimi", "last_name": "Nakagawa", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Oda", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Ueha", "name": null }, { "creator_type": "author", "first_name": "Kazuho", "last_name": "Ikeo", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Ogura", "name": null }, { "creator_type": "author", "first_name": "Kouji", "last_name": "Matsushima", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Shimano", "name": null } ], "identifiers": { "doi": { "normalized": "10.2337/db23-0212" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "37871012" } }, "mesh": [ { "descriptor": "Allostasis", "descriptor_ui": "D052636", "major_topic": true }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Annexins", "descriptor_ui": "D017302", "major_topic": false }, { "descriptor": "Calcium", "descriptor_ui": "D002118", "major_topic": false }, { "descriptor": "Diabetes Mellitus, Experimental", "descriptor_ui": "D003921", "major_topic": true }, { "descriptor": "Diabetes Mellitus, Type 2", "descriptor_ui": "D003924", "major_topic": true }, { "descriptor": "Gene Expression Profiling", "descriptor_ui": "D020869", "major_topic": false }, { "descriptor": "Insulin", "descriptor_ui": "D007328", "major_topic": false }, { "descriptor": "Insulin-Secreting Cells", "descriptor_ui": "D050417", "major_topic": true }, { "descriptor": "Islets of Langerhans", "descriptor_ui": "D007515", "major_topic": true }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred Strains", "descriptor_ui": "D008815", "major_topic": false }, { "descriptor": "Prediabetic State", "descriptor_ui": "D011236", "major_topic": true } ], "publication": { "conference_name": null, "date": "2023 Oct 23", "date_precision": "day", "issue": "", "normalized_date": "2023-10-23", "pages": "db230212", "proceedings_title": null, "publisher": "", "title": "Diabetes", "volume": "", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Single-cell transcriptome profiling of pancreatic islets from early diabetic mice identifies Anxa10 for Ca2+ allostasis toward beta-cell failure.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Inflammatory rhabdomyoblastic tumors (IRMTs) are newly recognized skeletal muscle tumors with uncertain malignant potential. We investigated 13 IRMTs using clinicopathological, genetic, and epigenetic methods. The cohort included 7 men and 6 women, aged 23-80 years (median, 50 years), of whom two had neurofibromatosis type 1. Most tumors occurred in the deep soft tissues of the lower limbs, head/neck, trunk wall, and retroperitoneum/pelvis. Two tumors involved the hypopharyngeal submucosa as polypoid masses. Eight tumors showed conventional histology of predominantly spindled cells with nuclear atypia, low mitotic activity, and massive inflammatory infiltrates. Three tumors showed atypical histology, including uniform epithelioid or plump cells and mitotically active histocytes. The remaining 2 tumors demonstrated malignant progression to rhabdomyosarcoma; one had additional IRMT histology and the other was a pure sarcoma. All 11 IRMTs without malignant progression exhibited indolent behavior at a median follow-up of 43 months. One of the 2 patients with IRMTs with malignant progression died of lung metastases. All IRMTs were positive for desmin and PAX7, whereas myogenin and MyoD1 were expressed in a subset of cases. Targeted next-generation sequencing identified pathogenic mutations in NF1 (5/8) and TP53 (4/8). All TP53 mutations co-occurred with NF1 mutations. TP53 variant allele frequency was much lower than that of NF1 in 2 cases. These tumors showed geographic (sub-clonal) strong p53 immunoreactivity, suggesting the secondary emergence of a TP53-mutant clone. DNA methylation-based copy number analysis conducted in 11 tumors revealed characteristic flat patterns with relative gains including chromosomes 5, 18, and/or 20-22 in most cases. Widespread loss of heterozygosity with retained biparental copies of these chromosomes was confirmed in 4 tumors analyzed via allele-specific profiling. Based on unsupervised DNA methylation analysis, none of the 11 tumors tested clustered with existing reference entities but formed a coherent group, although its specificity warrants further study.", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Toru", "last_name": "Odate", "name": null }, { "creator_type": "author", "first_name": "Kaishi", "last_name": "Satomi", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Kubo", "name": null }, { "creator_type": "author", "first_name": "Yuko", "last_name": "Matsushita", "name": null }, { "creator_type": "author", "first_name": "Toshihide", "last_name": "Ueno", "name": null }, { "creator_type": "author", "first_name": "Akira", "last_name": "Kurose", "name": null }, { "creator_type": "author", "first_name": "Kohei", "last_name": "Shomori", "name": null }, { "creator_type": "author", "first_name": "Tokiko", "last_name": "Nakai", "name": null }, { "creator_type": "author", "first_name": "Reiko", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Keiko", "last_name": "Segawa", "name": null }, { "creator_type": "author", "first_name": "Shusa", "last_name": "Ohshika", "name": null }, { "creator_type": "author", "first_name": "Naritomo", "last_name": "Miyake", "name": null }, { "creator_type": "author", "first_name": "Sayaka", "last_name": "Kudo", "name": null }, { "creator_type": "author", "first_name": "Tatsunori", "last_name": "Shimoi", "name": null }, { "creator_type": "author", "first_name": "Eisuke", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Motokiyo", "last_name": "Komiyama", "name": null }, { "creator_type": "author", "first_name": "Seiichi", "last_name": "Yoshimoto", "name": null }, { "creator_type": "author", "first_name": "Fumihiko", "last_name": "Nakatani", "name": null }, { "creator_type": "author", "first_name": "Akira", "last_name": "Kawai", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null }, { "creator_type": "author", "first_name": "Shinji", "last_name": "Kohsaka", "name": null }, { "creator_type": "author", "first_name": "Koichi", "last_name": "Ichimura", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Ichikawa", "name": null }, { "creator_type": "author", "first_name": "Akihiko", "last_name": "Yoshida", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.modpat.2023.100359" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "37871654" } }, "mesh": [ { "descriptor": "Biomarkers, Tumor", "descriptor_ui": "D014408", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Muscle Neoplasms", "descriptor_ui": "D019042", "major_topic": true }, { "descriptor": "Neurofibromatosis 1", "descriptor_ui": "D009456", "major_topic": true }, { "descriptor": "Rhabdomyosarcoma", "descriptor_ui": "D012208", "major_topic": true }, { "descriptor": "Sarcoma", "descriptor_ui": "D012509", "major_topic": true }, { "descriptor": "Soft Tissue Neoplasms", "descriptor_ui": "D012983", "major_topic": true } ], "publication": { "conference_name": null, "date": "2023 Oct 21", "date_precision": "day", "issue": "", "normalized_date": "2023-10-21", "pages": "100359", "proceedings_title": null, "publisher": "", "title": "Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc", "volume": "", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Inflammatory Rhabdomyoblastic Tumor: Clinicopathological and Molecular Analysis of 13 Cases.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The paraventricular nucleus of the thalamus (PVT) projects axons to multiple areas, mediates a wide range of behaviors, and exhibits regional heterogeneity in both functions and axonal projections. Still, questions regarding the cell types present in the PVT and the extent of their differences remain inadequately addressed. We applied single-cell RNA sequencing to depict the transcriptomic characteristics of mouse PVT neurons. We found that one of the most significant variances in the PVT transcriptome corresponded to the anterior-posterior axis. While the single-cell transcriptome classified PVT neurons into five types, our transcriptomic and histological analyses showed continuity among the cell types. We discovered that anterior and posterior subpopulations had nearly non-overlapping projection patterns, while another population showed intermediate patterns. In addition, these subpopulations responded differently to appetite-related neuropeptides, with their activation showing opposing effects on food consumption. Our studies unveiled the contrasts and the continuity of PVT neurons that underpin their function.", "classifications": [ { "id": "JPMJCR1926", "label": "JPMJCR1926", "researcher": "Hironobu Fujiwara", "type": "grant" }, { "id": "Fujiwara", "label": "Group Fujiwara", "parent": "Fujiwara", "type": "group" }, { "id": "Nikaido", "label": "Group Nikaido", "parent": "Fujiwara", "type": "group" }, { "id": "Fujiwara", "label": "Team Fujiwara", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yasuyuki", "last_name": "Shima", "name": null }, { "creator_type": "author", "first_name": "Henrik", "last_name": "Skibbe", "name": null }, { "creator_type": "author", "first_name": "Yohei", "last_name": "Sasagawa", "name": null }, { "creator_type": "author", "first_name": "Noriko", "last_name": "Fujimori", "name": null }, { "creator_type": "author", "first_name": "Yoshimi", "last_name": "Iwayama", "name": null }, { "creator_type": "author", "first_name": "Ayako", "last_name": "Isomura-Matoba", "name": null }, { "creator_type": "author", "first_name": "Minoru", "last_name": "Yano", "name": null }, { "creator_type": "author", "first_name": "Takumi", "last_name": "Ichikawa", "name": null }, { "creator_type": "author", "first_name": "Itoshi", "last_name": "Nikaido", "name": null }, { "creator_type": "author", "first_name": "Nobutaka", "last_name": "Hattori", "name": null }, { "creator_type": "author", "first_name": "Tadafumi", "last_name": "Kato", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.celrep.2023.113309" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "37862168" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Midline Thalamic Nuclei", "descriptor_ui": "D020644", "major_topic": true }, { "descriptor": "Paraventricular Hypothalamic Nucleus", "descriptor_ui": "D010286", "major_topic": true }, { "descriptor": "Thalamus", "descriptor_ui": "D013788", "major_topic": false }, { "descriptor": "Transcriptome", "descriptor_ui": "D059467", "major_topic": false } ], "publication": { "conference_name": null, "date": "2023 Oct 18", "date_precision": "day", "issue": "10", "normalized_date": "2023-10-18", "pages": "113309", "proceedings_title": null, "publisher": "", "title": "Cell reports", "volume": "42", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Distinctiveness and continuity in transcriptome and connectivity in the anterior-posterior axis of the paraventricular nucleus of the thalamus.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "", "classifications": [ { "id": "Nikaido", "label": "Group Nikaido", "parent": "Fujiwara", "type": "group" }, { "id": "Fujiwara", "label": "Team Fujiwara", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Hitomi", "last_name": "Takada", "name": null }, { "creator_type": "author", "first_name": "Yohei", "last_name": "Sasagawa", "name": null }, { "creator_type": "author", "first_name": "Mika", "last_name": "Yoshimura", "name": null }, { "creator_type": "author", "first_name": "Kaori", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Yoshimi", "last_name": "Iwayama", "name": null }, { "creator_type": "author", "first_name": "Tetsutaro", "last_name": "Hayashi", "name": null }, { "creator_type": "author", "first_name": "Ayako", "last_name": "Isomura-Matoba", "name": null }, { "creator_type": "author", "first_name": "Itoshi", "last_name": "Nikaido", "name": null }, { "creator_type": "author", "first_name": "Akira", "last_name": "Kurisaki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41467-023-41823-4" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "37848419" } }, "mesh": [], "publication": { "conference_name": null, "date": "2023 Oct 17", "date_precision": "day", "issue": "1", "normalized_date": "2023-10-17", "pages": "6540", "proceedings_title": null, "publisher": "", "title": "Nature communications", "volume": "14", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Author Correction: Single-cell transcriptomics uncovers EGFR signaling-mediated gastric progenitor cell differentiation in stomach homeostasis.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Chronic inflammation promotes development and progression of colorectal cancer (CRC). To comprehensively understand the molecular mechanisms underlying the development and progression of inflamed CRC, we perform in vivo screening and identify 142 genes that are frequently mutated in inflammation-associated colon tumors. These genes include senescence and TGFbeta-activin signaling genes. We find that TNFalpha can induce stemness and activate senescence signaling by enhancing cell plasticity in colonic epithelial cells, which could act as a selective pressure to mutate senescence-related genes in inflammation-associated colonic tumors. Furthermore, we show the efficacy of the Cdk4/6 inhibitor in vivo for inflammation-associated colonic tumors. Finally, we functionally validate that Arhgap5 and Mecom are tumor suppressor genes, providing possible therapeutic targets for CRC. Thus, we demonstrate the importance of the inactivation of senescence pathways in CRC development and progression in an inflammatory microenvironment, which can help progress toward precision medicine.", "classifications": [ { "id": "Okamoto", "label": "Group Okamoto", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Kana", "last_name": "Shimomura", "name": null }, { "creator_type": "author", "first_name": "Naoko", "last_name": "Hattori", "name": null }, { "creator_type": "author", "first_name": "Naoko", "last_name": "Iida", "name": null }, { "creator_type": "author", "first_name": "Yukari", "last_name": "Muranaka", "name": null }, { "creator_type": "author", "first_name": "Kotomi", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Yuichi", "last_name": "Shiraishi", "name": null }, { "creator_type": "author", "first_name": "Yasuhito", "last_name": "Arai", "name": null }, { "creator_type": "author", "first_name": "Natsuko", "last_name": "Hama", "name": null }, { "creator_type": "author", "first_name": "Tatsuhiro", "last_name": "Shibata", "name": null }, { "creator_type": "author", "first_name": "Daichi", "last_name": "Narushima", "name": null }, { "creator_type": "author", "first_name": "Mamoru", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Takamaru", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Okamoto", "name": null }, { "creator_type": "author", "first_name": "Haruna", "last_name": "Takeda", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41467-023-42228-z" }, "pmcid": { "normalized": "PMC10579371" }, "pmid": { "normalized": "37845228" } }, "mesh": [ { "descriptor": "Colonic Neoplasms", "descriptor_ui": "D003110", "major_topic": true }, { "descriptor": "Colorectal Neoplasms", "descriptor_ui": "D015179", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Inflammation", "descriptor_ui": "D007249", "major_topic": false }, { "descriptor": "Mutagenesis", "descriptor_ui": "D016296", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Tumor Microenvironment", "descriptor_ui": "D059016", "major_topic": false } ], "publication": { "conference_name": null, "date": "2023 Oct 16", "date_precision": "day", "issue": "1", "normalized_date": "2023-10-16", "pages": "6514", "proceedings_title": null, "publisher": "", "title": "Nature communications", "volume": "14", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Sleeping Beauty transposon mutagenesis identified genes and pathways involved in inflammation-associated colon tumor development.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Takaki", "last_name": "Akamine", "name": null }, { "creator_type": "author", "first_name": "Kazuo", "last_name": "Nakagawa", "name": null }, { "creator_type": "author", "first_name": "Kimiteru", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Hirokazu", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Masaya", "last_name": "Yotsukura", "name": null }, { "creator_type": "author", "first_name": "Yukihiro", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null }, { "creator_type": "author", "first_name": "Masahiko", "last_name": "Kusumoto", "name": null }, { "creator_type": "author", "first_name": "Shun-Ichi", "last_name": "Watanabe", "name": null } ], "identifiers": { "doi": { "normalized": "10.1245/s10434-023-14391-6" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "37843666" } }, "mesh": [], "publication": { "conference_name": null, "date": "2023 Oct 16", "date_precision": "day", "issue": "", "normalized_date": "2023-10-16", "pages": "", "proceedings_title": null, "publisher": "", "title": "Annals of surgical oncology", "volume": "", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "ASO Visual Abstract: Impact of 18F-FDG PET on TNM Staging and Prognosis in Thymic Epithelial Tumors.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "High-grade serous ovarian carcinoma (HGSOC) is the most lethal gynecological malignancy. To date, the profiles of gene mutations and copy number alterations in HGSOC have been well characterized. However, the patterns of epigenetic alterations and transcription factor dysregulation in HGSOC have not yet been fully elucidated. In this study, we performed integrative omics analyses of a series of stepwise HGSOC model cells originating from human fallopian tube secretory epithelial cells (HFTSECs) to investigate early epigenetic alterations in HGSOC tumorigenesis. Assay for transposase-accessible chromatin using sequencing (ATAC-seq), chromatin immunoprecipitation sequencing (ChIP-seq), and RNA sequencing (RNA-seq) methods were used to analyze HGSOC samples. Additionally, protein expression changes in target genes were confirmed using normal HFTSECs, serous tubal intraepithelial carcinomas (STICs), and HGSOC tissues. Transcription factor motif analysis revealed that the DNA-binding activity of the AP-1 complex and GATA family proteins was dysregulated during early tumorigenesis. The protein expression levels of JUN and FOSL2 were increased, and those of GATA6 and DAB2 were decreased in STIC lesions, which were associated with epithelial-mesenchymal transition (EMT) and proteasome downregulation. The genomic region around the FRA16D site, containing a cadherin cluster region, was epigenetically suppressed by oncogenic signaling. Proteasome inhibition caused the upregulation of chemokine genes, which may facilitate immune evasion during HGSOC tumorigenesis. Importantly, MEK inhibitor treatment reversed these oncogenic alterations, indicating its clinical effectiveness in a subgroup of patients with HGSOC. This result suggests that MEK inhibitor therapy may be an effective treatment option for chemotherapy-resistant HGSOC.", "classifications": [ { "id": "Hamamoto", "label": "Group Hamamoto", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Hidenori", "last_name": "Machino", "name": null }, { "creator_type": "author", "first_name": "Ai", "last_name": "Dozen", "name": null }, { "creator_type": "author", "first_name": "Mariko", "last_name": "Konaka", "name": null }, { "creator_type": "author", "first_name": "Masaaki", "last_name": "Komatsu", "name": null }, { "creator_type": "author", "first_name": "Kohei", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Noriko", "last_name": "Ikawa", "name": null }, { "creator_type": "author", "first_name": "Kanto", "last_name": "Shozu", "name": null }, { "creator_type": "author", "first_name": "Ken", "last_name": "Asada", "name": null }, { "creator_type": "author", "first_name": "Syuzo", "last_name": "Kaneko", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Tomoyasu", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Kentaro", "last_name": "Nakayama", "name": null }, { "creator_type": "author", "first_name": "Vassiliki", "last_name": "Saloura", "name": null }, { "creator_type": "author", "first_name": "Satoru", "last_name": "Kyo", "name": null }, { "creator_type": "author", "first_name": "Ryuji", "last_name": "Hamamoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s12276-023-01090-1" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "37779141" } }, "mesh": [ { "descriptor": "Carcinogenesis", "descriptor_ui": "D063646", "major_topic": false }, { "descriptor": "Cystadenocarcinoma, Serous", "descriptor_ui": "D018284", "major_topic": true }, { "descriptor": "Epigenesis, Genetic", "descriptor_ui": "D044127", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mitogen-Activated Protein Kinase Kinases", "descriptor_ui": "D020929", "major_topic": false }, { "descriptor": "Ovarian Neoplasms", "descriptor_ui": "D010051", "major_topic": true }, { "descriptor": "Proteasome Endopeptidase Complex", "descriptor_ui": "D046988", "major_topic": false }, { "descriptor": "Transcription Factors", "descriptor_ui": "D014157", "major_topic": false } ], "publication": { "conference_name": null, "date": "2023 Oct 2", "date_precision": "day", "issue": "", "normalized_date": "2023-10-02", "pages": "", "proceedings_title": null, "publisher": "", "title": "Experimental & molecular medicine", "volume": "", "year": 2023 }, "ssbd": { "database": [], "repository": [ "ssbd-repos-000372" ] }, "title": "Integrative analysis reveals early epigenetic alterations in high-grade serous ovarian carcinomas.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Small-cell lung cancer (SCLC) has a poor prognosis, emphasizing the necessity for developing new therapies. The de novo synthesis pathway of purine nucleotides, which is involved in the malignant growth of SCLC, has emerged as a novel therapeutic target. Purine nucleotides are supplied by two pathways: de novo and salvage. However, the role of the salvage pathway in SCLC and the differences in utilization and crosstalk between the two pathways remain largely unclear. Here, we found that deletion of the HPRT1 gene, which codes for the rate-limiting enzyme of the purine salvage pathway, significantly suppressed tumor growth in vivo in several SCLC cells. We also demonstrated that HPRT1 expression confers resistance to lemetrexol (LMX), an inhibitor of the purine de novo pathway. Interestingly, HPRT1-knockout had less effect on SCLC SBC-5 cells, which are more sensitive to LMX than other SCLC cell lines, suggesting that a preference for either the purine de novo or salvage pathway occurs in SCLC. Furthermore, metabolome analysis of HPRT1-knockout cells revealed increased intermediates in the pentose phosphate pathway and elevated metabolic flux in the purine de novo pathway, indicating compensated metabolism between the de novo and salvage pathways in purine nucleotide biosynthesis. These results suggest that HPRT1 has therapeutic implications in SCLC and provide fundamental insights into the regulation of purine nucleotide biosynthesis. Implications: SCLC tumors preferentially utilize either the de novo or salvage pathway in purine nucleotide biosynthesis, and HPRT1 has therapeutic implications in SCLC.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Sho", "last_name": "Tabata", "name": null }, { "creator_type": "author", "first_name": "Shigeki", "last_name": "Umemura", "name": null }, { "creator_type": "author", "first_name": "Miyu", "last_name": "Narita", "name": null }, { "creator_type": "author", "first_name": "Hibiki", "last_name": "Udagawa", "name": null }, { "creator_type": "author", "first_name": "Takamasa", "last_name": "Ishikawa", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Tsuboi", "name": null }, { "creator_type": "author", "first_name": "Koichi", "last_name": "Goto", "name": null }, { "creator_type": "author", "first_name": "Genichiro", "last_name": "Ishii", "name": null }, { "creator_type": "author", "first_name": "Katsuya", "last_name": "Tsuchihara", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Ochiai", "name": null }, { "creator_type": "author", "first_name": "Susumu S.", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Hideki", "last_name": "Makinoshima", "name": null } ], "identifiers": { "doi": { "normalized": "10.1158/1541-7786.mcr-23-0386" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "37773022" } }, "mesh": [ { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Hypoxanthine Phosphoribosyltransferase", "descriptor_ui": "D007041", "major_topic": false }, { "descriptor": "Lung Neoplasms", "descriptor_ui": "D008175", "major_topic": true }, { "descriptor": "Purine Nucleotides", "descriptor_ui": "D011685", "major_topic": false }, { "descriptor": "Purines", "descriptor_ui": "D011687", "major_topic": false }, { "descriptor": "Small Cell Lung Carcinoma", "descriptor_ui": "D055752", "major_topic": true } ], "publication": { "conference_name": null, "date": "2023 Sep 29", "date_precision": "day", "issue": "", "normalized_date": "2023-09-29", "pages": "", "proceedings_title": null, "publisher": "", "title": "Molecular cancer research : MCR", "volume": "", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Metabolic hallmarks for purine nucleotide biosynthesis in small-cell lung carcinoma.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: Preoperative fluorine-18-fluorodeoxyglucose positron emission tomography ((18)F-FDG PET) of thymic epithelial tumors (TETs) is well known for identifying malignant-grade TETs; however, its predictive power for determining locally advanced tumors, lymph node (LN) metastasis, and prognosis remains unknown. PATIENTS AND METHODS: We retrospectively evaluated patients with resectable TETs who were preoperatively assessed using (18)F-FDG PET from January 2012 to January 2023. The receiver operating characteristic curve was used to evaluate the cutoff value of the maximum standardized uptake value (SUVmax) to predict advanced-stage disease. Recurrence/progression-free survival (RFS/PFS) was analyzed using the Kaplan-Meier method. The staging was classified according to the tumor-node-metastasis system. RESULTS: Our study included 177 patients; 145 (81.9%) had pathological early-stage TET (stage I or II), and 32 (19.1%) had advanced stage (stage III or IV). The area under the curve value for predicting the advanced stage was 0.903, and the cutoff value was 5.6 (sensitivity 81.3%, specificity 84.8%). SUVmax > 5.6 was associated with worse prognosis for RFS/PFS. LN metastasis was preoperatively detected by FDG uptake in 30.8% of patients with pathological LN positivity, whereas LN metastasis was not pathologically detected in patients with SUVmax < 5.9. In patients with advanced-stage TETs, LN recurrence was more frequent in patients who were preoperatively detected by (18)F-FDG PET than those who were not (75.0% versus 7.1%). CONCLUSIONS: (18)F-FDG PET is a potentially valuable tool for predicting advanced stage and poor prognosis of recurrence in patients with TETs. SUVmax can help thoracic surgeons to guide them in selecting appropriate therapeutic strategies for TETs.", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Takaki", "last_name": "Akamine", "name": null }, { "creator_type": "author", "first_name": "Kazuo", "last_name": "Nakagawa", "name": null }, { "creator_type": "author", "first_name": "Kimiteru", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Hirokazu", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Masaya", "last_name": "Yotsukura", "name": null }, { "creator_type": "author", "first_name": "Yukihiro", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null }, { "creator_type": "author", "first_name": "Masahiko", "last_name": "Kusumoto", "name": null }, { "creator_type": "author", "first_name": "Shun-Ichi", "last_name": "Watanabe", "name": null } ], "identifiers": { "doi": { "normalized": "10.1245/s10434-023-14328-z" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "37743455" } }, "mesh": [ { "descriptor": "Fluorodeoxyglucose F18", "descriptor_ui": "D019788", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Lymphatic Metastasis", "descriptor_ui": "D008207", "major_topic": false }, { "descriptor": "Neoplasm Staging", "descriptor_ui": "D009367", "major_topic": false }, { "descriptor": "Neoplasms, Glandular and Epithelial", "descriptor_ui": "D009375", "major_topic": true }, { "descriptor": "Positron Emission Tomography Computed Tomography", "descriptor_ui": "D000072078", "major_topic": false }, { "descriptor": "Positron-Emission Tomography", "descriptor_ui": "D049268", "major_topic": false }, { "descriptor": "Prognosis", "descriptor_ui": "D011379", "major_topic": false }, { "descriptor": "Radiopharmaceuticals", "descriptor_ui": "D019275", "major_topic": false }, { "descriptor": "Retrospective Studies", "descriptor_ui": "D012189", "major_topic": false }, { "descriptor": "Thymus Neoplasms", "descriptor_ui": "D013953", "major_topic": false } ], "publication": { "conference_name": null, "date": "2023 Sep 25", "date_precision": "day", "issue": "", "normalized_date": "2023-09-25", "pages": "", "proceedings_title": null, "publisher": "", "title": "Annals of surgical oncology", "volume": "", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Impact of (18)F-FDG PET on TNM Staging and Prognosis in Thymic Epithelial Tumors.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "INTRODUCTION: Despite being a widely used screening questionnaire, there is no consensus on the most appropriate measurement model for the Alcohol Use Disorders Identification Test (AUDIT). Furthermore, there have been limited studies on its measurement invariance across cross-cultural subgroups, genders, and sexual orientations. AIMS: The present study aimed to examine the fit of different measurement models for the AUDIT and its measurement invariance across a wide range of subgroups by country, language, gender, and sexual orientation. METHODS: Responses concerning past-year alcohol use from the participants of the cross-sectional International Sex Survey were considered (N = 62,943; M(age): 32.73; SD = 12.59). Confirmatory factor analysis, as well as measurement invariance tests were performed for 21 countries, 14 languages, three genders, and four sexual-orientation subgroups that met the minimum sample size requirement for inclusion in these analyses. RESULTS: A two-factor model with factors describing 'alcohol use' (items 1-3) and 'alcohol problems' (items 4-10) showed the best model fit across countries, languages, genders, and sexual orientations. For the former two, scalar and latent mean levels of invariance were reached considering different criteria. For gender and sexual orientation, a latent mean level of invariance was reached. CONCLUSIONS: In line with the two-factor model, the calculation of separate alcohol-use and alcohol-problem scores is recommended when using the AUDIT. The high levels of measurement invariance achieved for the AUDIT support its use in cross-cultural research, capable also of meaningful comparisons among genders and sexual orientations.", "classifications": [ { "id": "Fujiwara", "label": "Group Fujiwara", "parent": "Fujiwara", "type": "group" }, { "id": "Fujiwara", "label": "Team Fujiwara", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Zsolt", "last_name": "Horvath", "name": null }, { "creator_type": "author", "first_name": "Lena", "last_name": "Nagy", "name": null }, { "creator_type": "author", "first_name": "Monika", "last_name": "Koos", "name": null }, { "creator_type": "author", "first_name": "Shane W.", "last_name": "Kraus", "name": null }, { "creator_type": "author", "first_name": "Zsolt", "last_name": "Demetrovics", "name": null }, { "creator_type": "author", "first_name": "Marc N.", "last_name": "Potenza", "name": null }, { "creator_type": "author", "first_name": "Rafael", "last_name": "Ballester-Arnal", "name": null }, { "creator_type": "author", "first_name": "Dominik", "last_name": "Batthyany", "name": null }, { "creator_type": "author", "first_name": "Sophie", "last_name": "Bergeron", "name": null }, { "creator_type": "author", "first_name": "Joel", "last_name": "Billieux", "name": null }, { "creator_type": "author", "first_name": "Peer", "last_name": "Briken", "name": null }, { "creator_type": "author", "first_name": "Julius", "last_name": "Burkauskas", "name": null }, { "creator_type": "author", "first_name": "Georgina", "last_name": "Cardenas-Lopez", "name": null }, { "creator_type": "author", "first_name": "Joana", "last_name": "Carvalho", "name": null }, { "creator_type": "author", "first_name": "Jesus", "last_name": "Castro-Calvo", "name": null }, { "creator_type": "author", "first_name": "Lijun", "last_name": "Chen", "name": null }, { "creator_type": "author", "first_name": "Giacomo", "last_name": "Ciocca", "name": null }, { "creator_type": "author", "first_name": "Ornella", "last_name": "Corazza", "name": null }, { "creator_type": "author", "first_name": "Rita", "last_name": "Csako", "name": null }, { "creator_type": "author", "first_name": "David P.", "last_name": "Fernandez", "name": null }, { "creator_type": "author", "first_name": "Hironobu", "last_name": "Fujiwara", "name": null }, { "creator_type": "author", "first_name": "Elaine F.", "last_name": "Fernandez", "name": null }, { "creator_type": "author", "first_name": "Johannes", "last_name": "Fuss", "name": null }, { "creator_type": "author", "first_name": "Roman", "last_name": "Gabrhelik", "name": null }, { "creator_type": "author", "first_name": "Ateret", "last_name": "Gewirtz-Meydan", "name": null }, { "creator_type": "author", "first_name": "Biljana", "last_name": "Gjoneska", "name": null }, { "creator_type": "author", "first_name": "Mateusz", "last_name": "Gola", "name": null }, { "creator_type": "author", "first_name": "Joshua B.", "last_name": "Grubbs", "name": null }, { "creator_type": "author", "first_name": "Hashim T.", "last_name": "Hashim", "name": null }, { "creator_type": "author", "first_name": "Md Saiful", "last_name": "Islam", "name": null }, { "creator_type": "author", "first_name": "Mustafa", "last_name": "Ismail", "name": null }, { "creator_type": "author", "first_name": "Martha C.", "last_name": "Jimenez-Martinez", "name": null }, { "creator_type": "author", "first_name": "Tanja", "last_name": "Jurin", "name": null }, { "creator_type": "author", "first_name": "Ondrej", "last_name": "Kalina", "name": null }, { "creator_type": "author", "first_name": "Verena", "last_name": "Klein", "name": null }, { "creator_type": "author", "first_name": "Andras", "last_name": "Kolto", "name": null }, { "creator_type": "author", "first_name": "Sang-Kyu", "last_name": "Lee", "name": null }, { "creator_type": "author", "first_name": "Karol", "last_name": "Lewczuk", "name": null }, { "creator_type": "author", "first_name": "Chung-Ying", "last_name": "Lin", "name": null }, { "creator_type": "author", "first_name": "Christine", "last_name": "Lochner", "name": null }, { "creator_type": "author", "first_name": "Silvia", "last_name": "Lopez-Alvarado", "name": null }, { "creator_type": "author", "first_name": "Katerina", "last_name": "Lukavska", "name": null }, { "creator_type": "author", "first_name": "Percy", "last_name": "Mayta-Tristan", "name": null }, { "creator_type": "author", "first_name": "Dan J.", "last_name": "Miller", "name": null }, { "creator_type": "author", "first_name": "Olga", "last_name": "Orosova", "name": null }, { "creator_type": "author", "first_name": "Gabor", "last_name": "Orosz", "name": null }, { "creator_type": "author", "first_name": "Fernando P.", "last_name": "Ponce", "name": null }, { "creator_type": "author", "first_name": "Gonzalo R.", "last_name": "Quintana", "name": null }, { "creator_type": "author", "first_name": "Gabriel C.", "last_name": "Quintero Garzola", "name": null }, { "creator_type": "author", "first_name": "Jano", "last_name": "Ramos-Diaz", "name": null }, { "creator_type": "author", "first_name": "Kevin", "last_name": "Rigaud", "name": null }, { "creator_type": "author", "first_name": "Ann", "last_name": "Rousseau", "name": null }, { "creator_type": "author", "first_name": "Marco De Tubino", "last_name": "Scanavino", "name": null }, { "creator_type": "author", "first_name": "Marion K.", "last_name": "Schulmeyer", "name": null }, { "creator_type": "author", "first_name": "Pratap", "last_name": "Sharan", "name": null }, { "creator_type": "author", "first_name": "Mami", "last_name": "Shibata", "name": null }, { "creator_type": "author", "first_name": "Sheikh", "last_name": "Shoib", "name": null }, { "creator_type": "author", "first_name": "Vera", "last_name": "Sigre-Leiros", "name": null }, { "creator_type": "author", "first_name": "Luke", "last_name": "Sniewski", "name": null }, { "creator_type": "author", "first_name": "Ognen", "last_name": "Spasovski", "name": null }, { "creator_type": "author", "first_name": "Vesta", "last_name": "Steibliene", "name": null }, { "creator_type": "author", "first_name": "Dan J.", "last_name": "Stein", "name": null }, { "creator_type": "author", "first_name": "Julian", "last_name": "Strizek", "name": null }, { "creator_type": "author", "first_name": "Meng-Che", "last_name": "Tsai", "name": null }, { "creator_type": "author", "first_name": "Berk C.", "last_name": "Unsal", "name": null }, { "creator_type": "author", "first_name": "Marie-Pier", "last_name": "Vaillancourt-Morel", "name": null }, { "creator_type": "author", "first_name": "Marie Claire", "last_name": "Van Hout", "name": null }, { "creator_type": "author", "first_name": "Beata", "last_name": "Bothe", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.comppsych.2023.152427" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "37782987" } }, "mesh": [ { "descriptor": "Alcoholism", "descriptor_ui": "D000437", "major_topic": true }, { "descriptor": "Cross-Cultural Comparison", "descriptor_ui": "D003431", "major_topic": false }, { "descriptor": "Cross-Sectional Studies", "descriptor_ui": "D003430", "major_topic": false }, { "descriptor": "Factor Analysis, Statistical", "descriptor_ui": "D005163", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Psychometrics", "descriptor_ui": "D011594", "major_topic": false }, { "descriptor": "Reproducibility of Results", "descriptor_ui": "D015203", "major_topic": false }, { "descriptor": "Sexual Behavior", "descriptor_ui": "D012725", "major_topic": false }, { "descriptor": "Surveys and Questionnaires", "descriptor_ui": "D011795", "major_topic": false } ], "publication": { "conference_name": null, "date": "2023 Sep 23", "date_precision": "day", "issue": "", "normalized_date": "2023-09-23", "pages": "152427", "proceedings_title": null, "publisher": "", "title": "Comprehensive psychiatry", "volume": "127", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Psychometric properties of the Alcohol Use Disorders Identification Test (AUDIT) across cross-cultural subgroups, genders, and sexual orientations: Findings from the International Sex Survey (ISS).", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: Delta-like ligand 3 (DLL3) is a therapeutic target in small-cell lung cancer (SCLC). However, how DLL3 expression status affects the tumor microenvironment (TME) and clinical outcomes in SCLC remains unclear. METHODS: This retrospective study included patients with postoperative limited-stage (LS)-SCLC and extensive-stage (ES)-SCLC treated with platinum and etoposide (PE) plus anti-programmed cell death ligand 1 (PD-L1) antibody. We investigated the relationship of DLL3 expression with TME, mutation status, tumor neoantigens, and immunochemotherapy. RESULTS: In the LS-SCLC cohort (n = 59), whole-exome sequencing revealed that DLL3(High) cases had significantly more neoantigens (P = 0.004) and a significantly higher rate of the signature SBS4 associated with smoking (P = 0.02) than DLL3(Low) cases. Transcriptome analysis in the LS-SCLC cohort revealed that DLL3(High) cases had significantly suppressed immune-related pathways and dendritic cell (DC) function. SCLC with DLL3(High) had significantly lower proportions of T cells, macrophages, and DCs than those with DLL3(Low). In the ES-SCLC cohort (n = 30), the progression-free survival associated with PE plus anti-PD-L1 antibody was significantly worse in DLL3(High) cases than in DLL3(Low) cases (4.7 vs. 7.4 months, P = 0.01). CONCLUSIONS: Although SCLC with DLL3(High) had a higher neoantigen load, these tumors were resistant to immunochemotherapy due to suppressed tumor immunity by inhibiting antigen-presenting functions.", "classifications": [ { "id": "Hamamoto", "label": "Group Hamamoto", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Masayuki", "last_name": "Shirasawa", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Kouya", "last_name": "Shiraishi", "name": null }, { "creator_type": "author", "first_name": "Naoko", "last_name": "Goto", "name": null }, { "creator_type": "author", "first_name": "Shigehiro", "last_name": "Yagishita", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Imabayashi", "name": null }, { "creator_type": "author", "first_name": "Yuji", "last_name": "Matsumoto", "name": null }, { "creator_type": "author", "first_name": "Ken", "last_name": "Masuda", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Shinno", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Okuma", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Goto", "name": null }, { "creator_type": "author", "first_name": "Hidehito", "last_name": "Horinouchi", "name": null }, { "creator_type": "author", "first_name": "Masaya", "last_name": "Yotsukura", "name": null }, { "creator_type": "author", "first_name": "Yukihiro", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Kazuo", "last_name": "Nakagawa", "name": null }, { "creator_type": "author", "first_name": "Katsuhiko", "last_name": "Naoki", "name": null }, { "creator_type": "author", "first_name": "Takaaki", "last_name": "Tsuchida", "name": null }, { "creator_type": "author", "first_name": "Ryuji", "last_name": "Hamamoto", "name": null }, { "creator_type": "author", "first_name": "Noboru", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Noriko", "last_name": "Motoi", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Kohno", "name": null }, { "creator_type": "author", "first_name": "Shun-Ichi", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Yuichiro", "last_name": "Ohe", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41416-023-02427-3" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "37731022" } }, "mesh": [ { "descriptor": "Etoposide", "descriptor_ui": "D005047", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Intracellular Signaling Peptides and Proteins", "descriptor_ui": "D047908", "major_topic": false }, { "descriptor": "Ligands", "descriptor_ui": "D008024", "major_topic": false }, { "descriptor": "Lung Neoplasms", "descriptor_ui": "D008175", "major_topic": true }, { "descriptor": "Membrane Proteins", "descriptor_ui": "D008565", "major_topic": false }, { "descriptor": "Retrospective Studies", "descriptor_ui": "D012189", "major_topic": false }, { "descriptor": "Small Cell Lung Carcinoma", "descriptor_ui": "D055752", "major_topic": true }, { "descriptor": "Tumor Microenvironment", "descriptor_ui": "D059016", "major_topic": false } ], "publication": { "conference_name": null, "date": "2023 Sep 20", "date_precision": "day", "issue": "", "normalized_date": "2023-09-20", "pages": "", "proceedings_title": null, "publisher": "", "title": "British journal of cancer", "volume": "", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Tumor microenvironment-mediated immune profiles and efficacy of anti-PD-L1 antibody plus chemotherapy stratified by DLL3 expression in small-cell lung cancer.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Cell spheroids offer alternative in vitro cell models to monolayer cultured cells because they express complexities similar to those of in vivo tissues, such as cellular responses to drugs and chemicals. Raman spectroscopy emerged as a powerful analytical tool for detecting chemical changes in living cells because it nondestructively provides vibrational information regarding a target. Although multiple iterations are required in drug screening to determine drugs to treat cell spheroids and assess the inter-spheroid heterogeneity, current Raman applications used in spheroids analysis allow the observation of only a few spheroids owing to the low throughput of Raman spectroscopy. In this study, we developed a multifocal Raman spectrophotometer that enables simultaneous analysis of multiple spheroids in separate wells of a regular 96-well plate. By utilizing 96 focal spots excitation and parallel signal collection, our system can improve the throughput by approximately 2 orders of magnitude compared to a conventional single-focus Raman microscope. The Raman spectra of HeLa cell spheroids treated with anticancer drugs and HepG2 cell spheroids treated with free fatty acids were measured simultaneously, and concentration-dependent cellular responses were observed in both studies. Using the multifocal Raman spectrophotometer, we rapidly observed chemical changes in spheroids, and thus, this system can facilitate the application of Raman spectroscopy in analyzing the cellular responses of spheroids.", "classifications": [ { "id": "Fujita", "label": "Group Fujita", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Hao-Xiang", "last_name": "Liao", "name": null }, { "creator_type": "author", "first_name": "Kazuki", "last_name": "Bando", "name": null }, { "creator_type": "author", "first_name": "Menglu", "last_name": "Li", "name": null }, { "creator_type": "author", "first_name": "Katsumasa", "last_name": "Fujita", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/acs.analchem.3c02129" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "37725051" } }, "mesh": [ { "descriptor": "Antineoplastic Agents", "descriptor_ui": "D000970", "major_topic": true }, { "descriptor": "HeLa Cells", "descriptor_ui": "D006367", "major_topic": false }, { "descriptor": "Hep G2 Cells", "descriptor_ui": "D056945", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Spectrum Analysis, Raman", "descriptor_ui": "D013059", "major_topic": true }, { "descriptor": "Spheroids, Cellular", "descriptor_ui": "D018874", "major_topic": true } ], "publication": { "conference_name": null, "date": "2023 Sep 19", "date_precision": "day", "issue": "", "normalized_date": "2023-09-19", "pages": "", "proceedings_title": null, "publisher": "", "title": "Analytical chemistry", "volume": "", "year": 2023 }, "ssbd": { "database": [ "ssbd-database-000371" ], "repository": [ "ssbd-repos-000371" ] }, "title": "Multifocal Raman Spectrophotometer for Examining Drug-Induced and Chemical-Induced Cellular Changes in 3D Cell Spheroids.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "All aromatic C-H bonds of triphenylphosphine (PPh(3)) were efficiently replaced by C-D bonds using Ru/C and Ir/C co-catalysts in 2-PrOH and D(2)O, an inexpensive deuterium source. Furthermore, non-radioactive and safe deuterium-incorporated Mito-Q (drug candidate) was prepared from deuterated PPh(3) and used for the live-cell Raman imaging to evaluate the mitochondrial uptake.", "classifications": [ { "id": "Nakabayashi", "label": "Group Nakabayashi", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Shogo", "last_name": "Moriyama", "name": null }, { "creator_type": "author", "first_name": "Miyu", "last_name": "Mae", "name": null }, { "creator_type": "author", "first_name": "Daiki", "last_name": "Shibata", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Yamakoshi", "name": null }, { "creator_type": "author", "first_name": "Shinji", "last_name": "Kajimoto", "name": null }, { "creator_type": "author", "first_name": "Takakazu", "last_name": "Nakabayashi", "name": null }, { "creator_type": "author", "first_name": "Takayoshi", "last_name": "Ishimoto", "name": null }, { "creator_type": "author", "first_name": "Kaiki", "last_name": "Mogi", "name": null }, { "creator_type": "author", "first_name": "Hironao", "last_name": "Sajiki", "name": null }, { "creator_type": "author", "first_name": "Shuji", "last_name": "Akai", "name": null }, { "creator_type": "author", "first_name": "Yoshinari", "last_name": "Sawama", "name": null } ], "identifiers": { "doi": { "normalized": "10.1039/d3cc04410f" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "37721453" } }, "mesh": [ { "descriptor": "Deuterium", "descriptor_ui": "D003903", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mitochondria", "descriptor_ui": "D008928", "major_topic": false }, { "descriptor": "Organophosphorus Compounds", "descriptor_ui": "D009943", "major_topic": true }, { "descriptor": "Spectrum Analysis, Raman", "descriptor_ui": "D013059", "major_topic": false } ], "publication": { "conference_name": null, "date": "2023 Sep 18", "date_precision": "day", "issue": "", "normalized_date": "2023-09-18", "pages": "", "proceedings_title": null, "publisher": "", "title": "Chemical communications (Cambridge, England)", "volume": "", "year": 2023 }, "ssbd": { "database": [ "ssbd-database-000369" ], "repository": [ "ssbd-repos-000369" ] }, "title": "Multiple deuteration of triphenylphosphine and live-cell Raman imaging of deuterium-incorporated Mito-Q.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The interdigitated pavement cell shape is suggested to be mechanically rational at both the cellular and tissue levels, but the biological significance of the cell shape is not fully understood. In this study, we explored the potential importance of the jigsaw puzzle-like cell shape for cotyledon morphogenesis in Arabidopsis. We used a transgenic line overexpressing a Rho-like GTPase-interacting protein, ROP-INTERACTIVE CRIB MOTIF-CONTAINING PROTEIN 1 (RIC1), which causes simple elongation of pavement cells. Computer-assisted microscopic analyses, including virtual reality observation, revealed that RIC1 overexpression resulted in abnormal cotyledon shapes with marginal protrusions, suggesting that the abnormal organ shape might be explained by changes in the pavement cell shape. Microscopic, biochemical and mechanical observations indicated that the pavement cell deformation might be due to reduction in the cell wall cellulose content with alteration of cortical microtubule organization. To examine our hypothesis that simple elongation of pavement cells leads to an abnormal shape with marginal protrusion of the cotyledon, we developed a mathematical model that examines the impact of planar cell growth geometry on the morphogenesis of the organ that is an assemblage of the cells. Computer simulations supported experimental observations that elongated pavement cells resulted in an irregular cotyledon shape, suggesting that marginal protrusions were due to local growth variation possibly caused by stochastic bias in the direction of cell elongation cannot be explained only by polarity-based cell elongation, but that an organ-level regulatory mechanism is required.", "classifications": [ { "id": "JPMJCR2121", "label": "JPMJCR2121", "researcher": "Minako Ueda", "type": "grant" }, { "id": "Higaki", "label": "Group Higaki", "parent": "Ueda", "type": "group" }, { "id": "Ueda", "label": "Group Ueda", "parent": "Ueda", "type": "group" }, { "id": "Ueda", "label": "Team Ueda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Kotomi", "last_name": "Kikukawa", "name": null }, { "creator_type": "author", "first_name": "Hisako", "last_name": "Takigawa-Imamura", "name": null }, { "creator_type": "author", "first_name": "Kouichi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Toshihisa", "last_name": "Kotake", "name": null }, { "creator_type": "author", "first_name": "Takumi", "last_name": "Higaki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1093/pcp/pcad094" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "37718531" } }, "mesh": [ { "descriptor": "Arabidopsis", "descriptor_ui": "D017360", "major_topic": true }, { "descriptor": "Arabidopsis Proteins", "descriptor_ui": "D029681", "major_topic": true }, { "descriptor": "Cell Shape", "descriptor_ui": "D048430", "major_topic": false }, { "descriptor": "Cotyledon", "descriptor_ui": "D018548", "major_topic": false }, { "descriptor": "Microtubule-Associated Proteins", "descriptor_ui": "D008869", "major_topic": false }, { "descriptor": "Microtubules", "descriptor_ui": "D008870", "major_topic": false }, { "descriptor": "Plant Leaves", "descriptor_ui": "D018515", "major_topic": false } ], "publication": { "conference_name": null, "date": "2023 Sep 18", "date_precision": "day", "issue": "", "normalized_date": "2023-09-18", "pages": "pcad094", "proceedings_title": null, "publisher": "", "title": "Plant & cell physiology", "volume": "", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Smooth Elongation of Pavement Cells Induced by RIC1 Overexpression Leads to Marginal Protrusions of the Cotyledon in Arabidopsis thaliana.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Guanosine triphosphate (GTP) and adenosine triphosphate (ATP) are essential nucleic acid building blocks and serve as energy molecules for a wide range of cellular reactions. Cellular GTP concentration fluctuates independently of ATP and is significantly elevated in numerous cancers, contributing to malignancy. Quantitative measurement of ATP and GTP has become increasingly important to elucidate how concentration changes regulate cell function. Liquid chromatography-coupled mass spectrometry (LC-MS) and capillary electrophoresis-coupled MS (CE-MS) are powerful methods widely used for the identification and quantification of biological metabolites. However, these methods have limitations related to specialized instrumentation and expertise, low throughput, and high costs. Here, we introduce a novel quantitative method for GTP concentration monitoring (GTP-quenching resonance energy transfer (QRET)) in homogenous cellular extracts. CE-MS analysis along with pharmacological control of cellular GTP levels shows that GTP-QRET possesses high dynamic range and accuracy. Furthermore, we combined GTP-QRET with luciferase-based ATP detection, leading to a new technology, termed QT-Luc(GTP&ATP), enabling high-throughput compatible dual monitoring of cellular GTP and ATP in a homogenous fashion. Collectively, GTP-QRET and QT-Luc(GTP&ATP) offer a unique, high-throughput opportunity to explore cellular energy metabolism, serving as a powerful platform for the development of novel therapeutics and extending its usability across a range of disciplines.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Kari", "last_name": "Kopra", "name": null }, { "creator_type": "author", "first_name": "Randa", "last_name": "Mahran", "name": null }, { "creator_type": "author", "first_name": "Titta", "last_name": "Yli-Hollo", "name": null }, { "creator_type": "author", "first_name": "Sho", "last_name": "Tabata", "name": null }, { "creator_type": "author", "first_name": "Emmiliisa", "last_name": "Vuorinen", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Fujii", "name": null }, { "creator_type": "author", "first_name": "Iida", "last_name": "Vuorinen", "name": null }, { "creator_type": "author", "first_name": "Aki", "last_name": "Ogawa-Iio", "name": null }, { "creator_type": "author", "first_name": "Akiyoshi", "last_name": "Hirayama", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Atsuo T.", "last_name": "Sasaki", "name": null }, { "creator_type": "author", "first_name": "Harri", "last_name": "Harma", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/s00216-023-04944-9" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "37714971" } }, "mesh": [ { "descriptor": "Adenosine", "descriptor_ui": "D000241", "major_topic": true }, { "descriptor": "Adenosine Triphosphate", "descriptor_ui": "D000255", "major_topic": true }, { "descriptor": "Chromatography, Liquid", "descriptor_ui": "D002853", "major_topic": false }, { "descriptor": "Guanosine", "descriptor_ui": "D006151", "major_topic": false }, { "descriptor": "Guanosine Triphosphate", "descriptor_ui": "D006160", "major_topic": false } ], "publication": { "conference_name": null, "date": "2023 Sep 16", "date_precision": "day", "issue": "", "normalized_date": "2023-09-16", "pages": "", "proceedings_title": null, "publisher": "", "title": "Analytical and bioanalytical chemistry", "volume": "", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Homogeneous luminescent quantitation of cellular guanosine and adenosine triphosphates (GTP and ATP) using QT-Luc(GTP&ATP) assay.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "INTRODUCTION: Morphologic and molecular data for staging of multifocal lung squamous cell carcinomas (LSCC) are limited. In this study, whole exome sequencing (WES) was used as the gold standard to determine if multifocal LSCC represented separate primary cancers (SPLC) or intrapulmonary metastases (IPM). Genomic profiles were compared to the comprehensive morphologic assessment. METHODS: WES was performed on 20 tumor pairs of multifocal LSCC and matched normal lymph nodes using the Illumina NovaSeq6000 S4-Xp (Illumina, San Diego, CA). WES clonal and subclonal analysis data were compared with histological assessment by 16 thoracic pathologists. Additionally, the immune gene profiling of the study cases was characterized by the HTG EdgeSeq Precision Immuno-Oncology Panel. RESULTS: By WES data, eleven cases were classified as SPLC, while seven cases were IPM. Two cases were technically suboptimal. Analysis showed marked genomic and immunogenic heterogeneity, but immune gene expression profiles highly correlated with mutation profiles. Tumors classified as IPM have a large number of shared mutations (ranging from 33.5% to 80.7%) The agreement between individual morphological assessments for each case and WES was 58.3%. One case was unanimously interpreted morphologically as IPM and was in agreement with WES. In a further 17 cases, the number of pathologists whose morphological interpretation was in agreement with WES ranged from two (1 case) up to fifteen pathologists (1 case) per case. Pathologists showed a fair inter-observer agreement in the morphologic staging of multiple LSCC, with an overall kappa of 0.232. CONCLUSIONS: Staging of multifocal LSCC based on morphologic assessment is unreliable. Comprehensive genomic analyses should be adopted for the staging of multifocal LSCC.", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Sanja", "last_name": "Dacic", "name": null }, { "creator_type": "author", "first_name": "Xuanye", "last_name": "Cao", "name": null }, { "creator_type": "author", "first_name": "Neus Bota-", "last_name": "Rabassedas", "name": null }, { "creator_type": "author", "first_name": "Beatriz", "last_name": "Sanchez-Espiridion", "name": null }, { "creator_type": "author", "first_name": "Sabina", "last_name": "Berezowska", "name": null }, { "creator_type": "author", "first_name": "Yuchen", "last_name": "Han", "name": null }, { "creator_type": "author", "first_name": "Jin-Haeng", "last_name": "Chung", "name": null }, { "creator_type": "author", "first_name": "Mary Beth", "last_name": "Beasley", "name": null }, { "creator_type": "author", "first_name": "Lin", "last_name": "Dongmei", "name": null }, { "creator_type": "author", "first_name": "David", "last_name": "Hwang", "name": null }, { "creator_type": "author", "first_name": "Mari", "last_name": "Mino-Kenudson", "name": null }, { "creator_type": "author", "first_name": "Yuko", "last_name": "Minami", "name": null }, { "creator_type": "author", "first_name": "Mauro", "last_name": "Papotti", "name": null }, { "creator_type": "author", "first_name": "Natasha", "last_name": "Rekhtman", "name": null }, { "creator_type": "author", "first_name": "Anja C.", "last_name": "Roden", "name": null }, { "creator_type": "author", "first_name": "Erik", "last_name": "Thunnissen", "name": null }, { "creator_type": "author", "first_name": "Ming-Sound", "last_name": "Tsao", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null }, { "creator_type": "author", "first_name": "Akihiko", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Linghua", "last_name": "Wang", "name": null }, { "creator_type": "author", "first_name": "Douglas J.", "last_name": "Hartman", "name": null }, { "creator_type": "author", "first_name": "Jacob A.", "last_name": "Jerome", "name": null }, { "creator_type": "author", "first_name": "Humam", "last_name": "Kadara", "name": null }, { "creator_type": "author", "first_name": "Teh-Ying", "last_name": "Chou", "name": null }, { "creator_type": "author", "first_name": "Ignacio", "last_name": "Wistuba", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.jtho.2023.09.275" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "37717856" } }, "mesh": [ { "descriptor": "Carcinoma, Non-Small-Cell Lung", "descriptor_ui": "D002289", "major_topic": true }, { "descriptor": "Carcinoma, Squamous Cell", "descriptor_ui": "D002294", "major_topic": true }, { "descriptor": "Genomics", "descriptor_ui": "D023281", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Lung", "descriptor_ui": "D008168", "major_topic": false }, { "descriptor": "Lung Neoplasms", "descriptor_ui": "D008175", "major_topic": true } ], "publication": { "conference_name": null, "date": "2023 Sep 15", "date_precision": "day", "issue": "", "normalized_date": "2023-09-15", "pages": "S1556-0864(23)01077-8", "proceedings_title": null, "publisher": "", "title": "Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer", "volume": "", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Genomic staging of multifocal lung squamous cell carcinomas is independent of the comprehensive morphologic assessment.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The extended tubular shape of root hairs is established by tip growth and concomitant hardening. Here, we demonstrate that a syntaxin of plants (SYP)123-vesicle-associated membrane protein (VAMP)727-dependent secretion system delivers secondary cell wall components for hardening the subapical zone and shank of Arabidopsis (Arabidopsis thaliana) root hairs. We found increased SYP123 localization at the plasma membrane of the subapical and shank zones compared to the tip region in elongating root hairs. Inhibition of phosphatidylinositol (PtdIns)(3,5)P2 production impaired SYP123 localization at the plasma membrane and SYP123-mediated root hair shank hardening. Moreover, root hair elongation in the syp123 mutant was insensitive to a PtdIns(3,5)P2 synthesis inhibitor. SYP123 interacts with both VAMP721 and VAMP727. syp123 and vamp727 mutants exhibited reduced shank cell wall stiffness due to impaired secondary cell wall component deposition. Based on these results, we conclude that SYP123 is involved in VAMP721-mediated conventional secretion for root hair elongation as well as in VAMP727-mediated secretory functions for the delivery of secondary cell wall components to maintain root hair tubular morphology.", "classifications": [ { "id": "Higaki", "label": "Group Higaki", "parent": "Ueda", "type": "group" }, { "id": "Ueda", "label": "Team Ueda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Tomoko", "last_name": "Hirano", "name": null }, { "creator_type": "author", "first_name": "Kazuo", "last_name": "Ebine", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Ueda", "name": null }, { "creator_type": "author", "first_name": "Takumi", "last_name": "Higaki", "name": null }, { "creator_type": "author", "first_name": "Takahiro", "last_name": "Watanabe-Nakayama", "name": null }, { "creator_type": "author", "first_name": "Hiroki", "last_name": "Konno", "name": null }, { "creator_type": "author", "first_name": "Hisako", "last_name": "Takigawa-Imamura", "name": null }, { "creator_type": "author", "first_name": "Masa H.", "last_name": "Sato", "name": null } ], "identifiers": { "doi": { "normalized": "10.1093/plcell/koad240" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "37713604" } }, "mesh": [ { "descriptor": "Arabidopsis", "descriptor_ui": "D017360", "major_topic": true }, { "descriptor": "Arabidopsis Proteins", "descriptor_ui": "D029681", "major_topic": true }, { "descriptor": "Cell Wall", "descriptor_ui": "D002473", "major_topic": false }, { "descriptor": "Cytoplasm", "descriptor_ui": "D003593", "major_topic": false }, { "descriptor": "Phosphatidylinositols", "descriptor_ui": "D010716", "major_topic": false }, { "descriptor": "Plant Roots", "descriptor_ui": "D018517", "major_topic": false }, { "descriptor": "R-SNARE Proteins", "descriptor_ui": "D050683", "major_topic": false }, { "descriptor": "SNARE Proteins", "descriptor_ui": "D050600", "major_topic": false } ], "publication": { "conference_name": null, "date": "2023 Sep 15", "date_precision": "day", "issue": "", "normalized_date": "2023-09-15", "pages": "koad240", "proceedings_title": null, "publisher": "", "title": "The Plant cell", "volume": "", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "The SYP123-VAMP727 SNARE complex delivers secondary cell wall components for root hair shank hardening in Arabidopsis.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Myxoid liposarcoma (MLS) is a common type of liposarcoma. It is characterized by variably lipogenic uniform cells in myxoid stroma with arborizing capillaries and DDIT3 fusion. Nuclear uniformity is the rule, which is maintained even in high-grade round cell examples. In this study, we conducted an in-depth investigation of four MLS tumors that demonstrated nuclear pleomorphism in three patients. These cases accounted for 2.1% of 142 patients with MLS. All patients were male aged 26, 33, and 49 years. Nuclear pleomorphism was observed in both primary and metastatic tumors in one patient, a primary tumor in one patient, and a metastatic tumor in another patient. Pleomorphism was severe in three tumors and moderate in one. Histology resembled that of dedifferentiated liposarcoma with myxoid features, pleomorphic liposarcoma with myxoid features, or myxoid pleomorphic liposarcoma in two tumors, pleomorphic sarcoma with focal cartilaginous and rhabdomyoblastic differentiation in one tumor, and epithelioid pleomorphic liposarcoma in one tumor. All tumors harbored FUS::DDIT3 fusions and immunohistochemically expressed DDIT3. All tumors had TP53 mutations, whereas previous specimens with uniform cytology from the same patients lacked TP53 mutations. One tumor showed RB1 deletion and complete loss of Rb expression, which was unclassifiable using DNA methylation-based methods. The rare occurrence of nuclear pleomorphism is underrecognized in MLS and increases the complexity to the diagnosis of liposarcoma. DDIT3 evaluation can be liberally considered in liposarcoma assessment even in the presence of nuclear pleomorphism.", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Naoki", "last_name": "Kojima", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Kubo", "name": null }, { "creator_type": "author", "first_name": "Taisuke", "last_name": "Mori", "name": null }, { "creator_type": "author", "first_name": "Kaishi", "last_name": "Satomi", "name": null }, { "creator_type": "author", "first_name": "Yuko", "last_name": "Matsushita", "name": null }, { "creator_type": "author", "first_name": "Shintaro", "last_name": "Iwata", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null }, { "creator_type": "author", "first_name": "Koichi", "last_name": "Ichimura", "name": null }, { "creator_type": "author", "first_name": "Akira", "last_name": "Kawai", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Ichikawa", "name": null }, { "creator_type": "author", "first_name": "Akihiko", "last_name": "Yoshida", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/s00428-023-03631-5" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "37704823" } }, "mesh": [ { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Liposarcoma", "descriptor_ui": "D008080", "major_topic": true }, { "descriptor": "Liposarcoma, Myxoid", "descriptor_ui": "D018208", "major_topic": true }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": false }, { "descriptor": "Soft Tissue Neoplasms", "descriptor_ui": "D012983", "major_topic": true } ], "publication": { "conference_name": null, "date": "2023 Sep 13", "date_precision": "day", "issue": "", "normalized_date": "2023-09-13", "pages": "", "proceedings_title": null, "publisher": "", "title": "Virchows Archiv : an international journal of pathology", "volume": "", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Myxoid liposarcoma with nuclear pleomorphism: a clinicopathological and molecular study.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "During periods of fasting, the body undergoes a metabolic shift from carbohydrate utilization to the use of fats and ketones as an energy source, as well as the inhibition of de novo lipogenesis and the initiation of gluconeogenesis in the liver. The transcription factor sterol regulatory element-binding protein-1 (SREBP-1), which plays a critical role in the regulation of lipogenesis, is suppressed during fasting, resulting in the suppression of hepatic lipogenesis. We previously demonstrated that the interaction of fasting-induced Kruppel-like factor 15 (KLF15) with liver X receptor (LXR) serves as the essential mechanism for the nutritional regulation of SREBP-1 expression. However, the underlying mechanisms of KLF15 induction during fasting remain unclear. In this study, we show that the glucocorticoid receptor (GR) regulates the hepatic expression of KLF15 and, subsequently, lipogenesis through the KLF15-SREBP-1 pathway during fasting. KLF15 is necessary for the suppression of SREBP-1 by GR, as demonstrated through experiments using KLF15 knockout mice. Additionally, we show that GR is involved in the fasting response, with heightened binding to the KLF15 enhancer. It has been widely known that the hypothalamic-pituitary-adrenal (HPA) axis regulates the secretion of glucocorticoids and plays a significant role in the metabolic response to undernutrition. These findings demonstrate the importance of the HPA axis-regulated GR-KLF15 pathway in the regulation of lipid metabolism in the liver during fasting.", "classifications": [ { "id": "Miyamoto", "label": "Group Miyamoto", "parent": "Wakamoto", "type": "group" }, { "id": "Wakamoto", "label": "Team Wakamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yoshinori", "last_name": "Takeuchi", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Murayama", "name": null }, { "creator_type": "author", "first_name": "Yuichi", "last_name": "Aita", "name": null }, { "creator_type": "author", "first_name": "Zahra", "last_name": "Mehrazad Saber", "name": null }, { "creator_type": "author", "first_name": "Samia", "last_name": "Karkoutly", "name": null }, { "creator_type": "author", "first_name": "Duhan", "last_name": "Tao", "name": null }, { "creator_type": "author", "first_name": "Kyoka", "last_name": "Katabami", "name": null }, { "creator_type": "author", "first_name": "Chen", "last_name": "Ye", "name": null }, { "creator_type": "author", "first_name": "Akito", "last_name": "Shikama", "name": null }, { "creator_type": "author", "first_name": "Yukari", "last_name": "Masuda", "name": null }, { "creator_type": "author", "first_name": "Yoshihiko", "last_name": "Izumida", "name": null }, { "creator_type": "author", "first_name": "Takafumi", "last_name": "Miyamoto", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Matsuzaka", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Kawakami", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Shimano", "name": null }, { "creator_type": "author", "first_name": "Naoya", "last_name": "Yahagi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/febs.16957" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "37702262" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Fasting", "descriptor_ui": "D005215", "major_topic": false }, { "descriptor": "Kruppel-Like Transcription Factors", "descriptor_ui": "D051741", "major_topic": false }, { "descriptor": "Lipogenesis", "descriptor_ui": "D050155", "major_topic": true }, { "descriptor": "Liver", "descriptor_ui": "D008099", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Promoter Regions, Genetic", "descriptor_ui": "D011401", "major_topic": false }, { "descriptor": "Receptors, Glucocorticoid", "descriptor_ui": "D011965", "major_topic": true }, { "descriptor": "Sterol Regulatory Element Binding Protein 1", "descriptor_ui": "D051780", "major_topic": false } ], "publication": { "conference_name": null, "date": "2023 Sep 13", "date_precision": "day", "issue": "", "normalized_date": "2023-09-13", "pages": "", "proceedings_title": null, "publisher": "", "title": "The FEBS journal", "volume": "", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "GR-KLF15 pathway controls hepatic lipogenesis during fasting.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Decitabine (DAC) is clinically used to treat myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). Our genome-wide CRISPR-dCas9 activation screen using MDS-derived AML cells indicates that mitotic regulation is critical for DAC resistance. DAC strongly induces abnormal mitosis (abscission failure or tripolar mitosis) in human myeloid tumors at clinical concentrations, especially in those with TP53 mutations or antecedent hematological disorders. This DAC-induced mitotic disruption and apoptosis are significantly attenuated in DNMT1-depleted cells. In contrast, overexpression of Dnmt1, but not the catalytically inactive mutant, enhances DAC-induced mitotic defects in myeloid tumors. We also demonstrate that DAC-induced mitotic disruption is enhanced by pharmacological inhibition of the ATR-CLSPN-CHK1 pathway. These data challenge the current assumption that DAC inhibits leukemogenesis through DNMT1 inhibition and subsequent DNA hypomethylation and highlight the potent activity of DAC to disrupt mitosis through aberrant DNMT1-DNA covalent bonds.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Tomohiro", "last_name": "Yabushita", "name": null }, { "creator_type": "author", "first_name": "Takumi", "last_name": "Chinen", "name": null }, { "creator_type": "author", "first_name": "Atsuya", "last_name": "Nishiyama", "name": null }, { "creator_type": "author", "first_name": "Shuhei", "last_name": "Asada", "name": null }, { "creator_type": "author", "first_name": "Ruka", "last_name": "Shimura", "name": null }, { "creator_type": "author", "first_name": "Tomoya", "last_name": "Isobe", "name": null }, { "creator_type": "author", "first_name": "Keita", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Naru", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Yutaka", "last_name": "Enomoto", "name": null }, { "creator_type": "author", "first_name": "Yosuke", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Tomofusa", "last_name": "Fukuyama", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Satoh", "name": null }, { "creator_type": "author", "first_name": "Keiko", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Kaori", "last_name": "Saitoh", "name": null }, { "creator_type": "author", "first_name": "Takamasa", "last_name": "Ishikawa", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Yasuhito", "last_name": "Nannya", "name": null }, { "creator_type": "author", "first_name": "Tatsuo", "last_name": "Fukagawa", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Nakanishi", "name": null }, { "creator_type": "author", "first_name": "Daiju", "last_name": "Kitagawa", "name": null }, { "creator_type": "author", "first_name": "Toshio", "last_name": "Kitamura", "name": null }, { "creator_type": "author", "first_name": "Susumu", "last_name": "Goyama", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.celrep.2023.113098" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "37714156" } }, "mesh": [ { "descriptor": "Adaptor Proteins, Signal Transducing", "descriptor_ui": "D048868", "major_topic": false }, { "descriptor": "Antimetabolites, Antineoplastic", "descriptor_ui": "D000964", "major_topic": false }, { "descriptor": "Azacitidine", "descriptor_ui": "D001374", "major_topic": true }, { "descriptor": "Decitabine", "descriptor_ui": "D000077209", "major_topic": false }, { "descriptor": "DNA", "descriptor_ui": "D004247", "major_topic": false }, { "descriptor": "DNA Methylation", "descriptor_ui": "D019175", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Leukemia, Myeloid, Acute", "descriptor_ui": "D015470", "major_topic": true } ], "publication": { "conference_name": null, "date": "2023 Sep 12", "date_precision": "day", "issue": "", "normalized_date": "2023-09-12", "pages": "113098", "proceedings_title": null, "publisher": "", "title": "Cell reports", "volume": "", "year": 2023 }, "ssbd": { "database": [ "ssbd-database-000368" ], "repository": [ "ssbd-repos-000368" ] }, "title": "Mitotic perturbation is a key mechanism of action of decitabine in myeloid tumor treatment.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes are interacting comorbidities of obesity, and increased hepatic de novo lipogenesis (DNL), driven by hyperinsulinemia and carbohydrate overload, contributes to their pathogenesis. Fatty acid synthase (FASN), a key enzyme of hepatic DNL, is upregulated in association with insulin resistance. However, the therapeutic potential of targeting FASN in hepatocytes for obesity-associated metabolic diseases is unknown. Here, we show that hepatic FASN deficiency differentially affects NAFLD and diabetes depending on the etiology of obesity. Hepatocyte-specific ablation of FASN ameliorated NAFLD and diabetes in melanocortin 4 receptor-deficient mice but not in mice with diet-induced obesity. In leptin-deficient mice, FASN ablation alleviated hepatic steatosis and improved glucose tolerance but exacerbated fed hyperglycemia and liver dysfunction. The beneficial effects of hepatic FASN deficiency on NAFLD and glucose metabolism were associated with suppression of DNL and attenuation of gluconeogenesis and fatty acid oxidation, respectively. The exacerbation of fed hyperglycemia by FASN ablation in leptin-deficient mice appeared attributable to impairment of hepatic glucose uptake triggered by glycogen accumulation and citrate-mediated inhibition of glycolysis. Further investigation of the therapeutic potential of hepatic FASN inhibition for NAFLD and diabetes in humans should thus consider the etiology of obesity.", "classifications": [ { "id": "Inaba", "label": "Group Inaba", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Toshiya", "last_name": "Matsukawa", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Yagi", "name": null }, { "creator_type": "author", "first_name": "Tohru", "last_name": "Uchida", "name": null }, { "creator_type": "author", "first_name": "Mashito", "last_name": "Sakai", "name": null }, { "creator_type": "author", "first_name": "Masaru", "last_name": "Mitsushima", "name": null }, { "creator_type": "author", "first_name": "Takao", "last_name": "Naganuma", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Yano", "name": null }, { "creator_type": "author", "first_name": "Yuka", "last_name": "Inaba", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Inoue", "name": null }, { "creator_type": "author", "first_name": "Keisuke", "last_name": "Yanagida", "name": null }, { "creator_type": "author", "first_name": "Masaaki", "last_name": "Uematsu", "name": null }, { "creator_type": "author", "first_name": "Kazuki", "last_name": "Nakao", "name": null }, { "creator_type": "author", "first_name": "Harumi", "last_name": "Nakao", "name": null }, { "creator_type": "author", "first_name": "Atsu", "last_name": "Aiba", "name": null }, { "creator_type": "author", "first_name": "Yoji", "last_name": "Nagashima", "name": null }, { "creator_type": "author", "first_name": "Tetsuya", "last_name": "Kubota", "name": null }, { "creator_type": "author", "first_name": "Naoto", "last_name": "Kubota", "name": null }, { "creator_type": "author", "first_name": "Yoshihiko", "last_name": "Izumida", "name": null }, { "creator_type": "author", "first_name": "Naoya", "last_name": "Yahagi", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Unoki-Kubota", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Kaburagi", "name": null }, { "creator_type": "author", "first_name": "Shun-Ichiro", "last_name": "Asahara", "name": null }, { "creator_type": "author", "first_name": "Yoshiaki", "last_name": "Kido", "name": null }, { "creator_type": "author", "first_name": "Hideo", "last_name": "Shindou", "name": null }, { "creator_type": "author", "first_name": "Michiko", "last_name": "Itoh", "name": null }, { "creator_type": "author", "first_name": "Yoshihiro", "last_name": "Ogawa", "name": null }, { "creator_type": "author", "first_name": "Shiro", "last_name": "Minami", "name": null }, { "creator_type": "author", "first_name": "Yasuo", "last_name": "Terauchi", "name": null }, { "creator_type": "author", "first_name": "Kazuyuki", "last_name": "Tobe", "name": null }, { "creator_type": "author", "first_name": "Kohjiro", "last_name": "Ueki", "name": null }, { "creator_type": "author", "first_name": "Masato", "last_name": "Kasuga", "name": null }, { "creator_type": "author", "first_name": "Michihiro", "last_name": "Matsumoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1172/jci.insight.161282" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "37681411" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Diabetes Mellitus, Type 2", "descriptor_ui": "D003924", "major_topic": true }, { "descriptor": "Fatty Acid Synthase, Type I", "descriptor_ui": "D054890", "major_topic": false }, { "descriptor": "Fatty Acid Synthases", "descriptor_ui": "D064429", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Hyperglycemia", "descriptor_ui": "D006943", "major_topic": true }, { "descriptor": "Leptin", "descriptor_ui": "D020738", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Nitric Oxide Synthase", "descriptor_ui": "D019001", "major_topic": false }, { "descriptor": "Non-alcoholic Fatty Liver Disease", "descriptor_ui": "D065626", "major_topic": true }, { "descriptor": "Obesity", "descriptor_ui": "D009765", "major_topic": false } ], "publication": { "conference_name": null, "date": "2023 Sep 8", "date_precision": "day", "issue": "17", "normalized_date": "2023-09-08", "pages": "e161282", "proceedings_title": null, "publisher": "", "title": "JCI insight", "volume": "8", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Hepatic FASN deficiency differentially affects nonalcoholic fatty liver disease and diabetes in mouse obesity models.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Tubulin, a heterodimer of alpha- and beta-tubulin, is a GTPase that assembles into microtubule (MT) polymers whose dynamic properties are intimately coupled to nucleotide hydrolysis. In cells, the organization and dynamics of MTs are further tuned by post-translational modifications (PTMs), which control the ability of MT-associated proteins (MAPs) and molecular motors to engage MTs. Detyrosination is a PTM of alpha-tubulin, wherein its C-terminal tyrosine residue is enzymatically removed by either the vasohibin (VASH) or MT-associated tyrosine carboxypeptidase (MATCAP) peptidases. How these enzymes generate specific patterns of MT detyrosination in cells is not known. Here, we use a novel antibody-based probe to visualize the formation of detyrosinated MTs in real time and employ single-molecule imaging of VASH1 bound to its regulatory partner small-vasohibin binding protein (SVBP) to understand the process of MT detyrosination in vitro and in cells. We demonstrate that the activity, but not binding, of VASH1/SVBP is much greater on mimics of guanosine triphosphate (GTP)-MTs than on guanosine diphosphate (GDP)-MTs. Given emerging data showing that tubulin subunits in GTP-MTs are in expanded conformation relative to tubulin subunits in GDP-MTs, we reasoned that the lattice conformation of MTs is a key factor that gates the activity of VASH1/SVBP. We show that Taxol, a drug known to expand the MT lattice, promotes MT detyrosination and that CAMSAP2 and CAMSAP3 are two MAPs that spatially regulate detyrosination in cells. Collectively, our work shows that VASH1/SVBP detyrosination is regulated by the conformational state of tubulin in the MT lattice and that this is spatially determined in cells by the activity of MAPs.", "classifications": [ { "id": "Higaki", "label": "Group Higaki", "parent": "Ueda", "type": "group" }, { "id": "Ueda", "label": "Team Ueda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yang", "last_name": "Yue", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Hotta", "name": null }, { "creator_type": "author", "first_name": "Takumi", "last_name": "Higaki", "name": null }, { "creator_type": "author", "first_name": "Kristen J.", "last_name": "Verhey", "name": null }, { "creator_type": "author", "first_name": "Ryoma", "last_name": "Ohi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.cub.2023.07.062" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "37716348" } }, "mesh": [ { "descriptor": "Guanosine Triphosphate", "descriptor_ui": "D006160", "major_topic": false }, { "descriptor": "Microtubules", "descriptor_ui": "D008870", "major_topic": true }, { "descriptor": "Paclitaxel", "descriptor_ui": "D017239", "major_topic": false }, { "descriptor": "Tubulin", "descriptor_ui": "D014404", "major_topic": true }, { "descriptor": "Tyrosine", "descriptor_ui": "D014443", "major_topic": false } ], "publication": { "conference_name": null, "date": "2023 Sep 5", "date_precision": "day", "issue": "", "normalized_date": "2023-09-05", "pages": "S0960-9822(23)01001-1", "proceedings_title": null, "publisher": "", "title": "Current biology : CB", "volume": "", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Microtubule detyrosination by VASH1/SVBP is regulated by the conformational state of tubulin in the lattice.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Growth regulation by estrogen in breast cancer 1 (GREB1) is involved in hormone-dependent and -independent tumor development (e.g., hepatoblastoma). In this study, we found that a GREB1 splicing variant, isoform 4 (Is4), which encodes C-terminal half of full-length GREB1, is specifically expressed via microphthalmia-associated transcription factor (MITF) in melanocytic melanoma, and that two MITF-binding E-box CANNTG motifs at the 5'-upstream region of GREB1 exon 19 are necessary for GREB1 Is4 transcription. MITF and GREB1 Is4 were strongly co-expressed in approximately 20% of the melanoma specimens evaluated (17/89 cases) and their expression was associated with tumor thickness. GREB1 Is4 silencing reduced melanoma cell proliferation in association with altered expression of cell proliferation-related genes in vitro. In addition, GREB1 Is4 targeting by antisense oligonucleotide (ASO) decreased melanoma xenograft tumor formation and GREB1 Is4 expression in a BRAF(V600E); PTEN(flox) melanoma mouse model promoted melanoma formation, demonstrating the crucial role of GREB1 Is4 for melanoma proliferation in vivo. GREB1 Is4 bound to CAD, the rate-limiting enzyme of pyrimidine metabolism, and metabolic flux analysis revealed that GREBI Is4 is necessary for pyrimidine synthesis. These results suggest that MITF-dependent GREB1 Is4 expression leads to melanoma proliferation and GREB1 Is4 represents a new molecular target in melanoma.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Koei", "last_name": "Shinzawa", "name": null }, { "creator_type": "author", "first_name": "Shinji", "last_name": "Matsumoto", "name": null }, { "creator_type": "author", "first_name": "Ryota", "last_name": "Sada", "name": null }, { "creator_type": "author", "first_name": "Akikazu", "last_name": "Harada", "name": null }, { "creator_type": "author", "first_name": "Kaori", "last_name": "Saitoh", "name": null }, { "creator_type": "author", "first_name": "Keiko", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Satsuki", "last_name": "Ikeda", "name": null }, { "creator_type": "author", "first_name": "Akiyoshi", "last_name": "Hirayama", "name": null }, { "creator_type": "author", "first_name": "Kazunori", "last_name": "Yokoi", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Tanemura", "name": null }, { "creator_type": "author", "first_name": "Keisuke", "last_name": "Nimura", "name": null }, { "creator_type": "author", "first_name": "Masahito", "last_name": "Ikawa", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Akira", "last_name": "Kikuchi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41388-023-02803-6" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "37658191" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Cell Proliferation", "descriptor_ui": "D049109", "major_topic": false }, { "descriptor": "Gene Expression Regulation, Neoplastic", "descriptor_ui": "D015972", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Melanoma", "descriptor_ui": "D008545", "major_topic": true }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Microphthalmia-Associated Transcription Factor", "descriptor_ui": "D051739", "major_topic": true }, { "descriptor": "Neoplasm Proteins", "descriptor_ui": "D009363", "major_topic": false }, { "descriptor": "Protein Isoforms", "descriptor_ui": "D020033", "major_topic": false }, { "descriptor": "Pyrimidines", "descriptor_ui": "D011743", "major_topic": false } ], "publication": { "conference_name": null, "date": "2023 Sep 1", "date_precision": "day", "issue": "", "normalized_date": "2023-09-01", "pages": "", "proceedings_title": null, "publisher": "", "title": "Oncogene", "volume": "", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "GREB1 isoform 4 is specifically transcribed by MITF and required for melanoma proliferation.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Red blood cells (RBCs) mediate cardioprotection via nitric oxide-like bioactivity, but the signaling and the identity of any mediator released by the RBCs remains unknown. We investigated whether RBCs exposed to hypoxia release a cardioprotective mediator and explored the nature of this mediator. Perfusion of isolated hearts subjected to ischemia-reperfusion with extracellular supernatant from mouse RBCs exposed to hypoxia resulted in improved postischemic cardiac function and reduced infarct size. Hypoxia increased extracellular export of cyclic guanosine monophosphate (cGMP) from mouse RBCs, and exogenous cGMP mimicked the cardioprotection induced by the supernatant. The protection induced by hypoxic RBCs was dependent on RBC-soluble guanylate cyclase and cGMP transport and was sensitive to phosphodiesterase 5 and activated cardiomyocyte protein kinase G. Oral administration of nitrate to mice to increase nitric oxide bioactivity further enhanced the cardioprotective effect of hypoxic RBCs. In a placebo-controlled clinical trial, a clear cardioprotective, soluble guanylate cyclase-dependent effect was induced by RBCs collected from patients randomized to 5 weeks nitrate-rich diet. It is concluded that RBCs generate and export cGMP as a response to hypoxia, mediating cardioprotection via a paracrine effect. This effect can be further augmented by a simple dietary intervention, suggesting preventive and therapeutic opportunities in ischemic heart disease.", "classifications": [ { "id": "Akaike", "label": "Group Akaike", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Jiangning", "last_name": "Yang", "name": null }, { "creator_type": "author", "first_name": "Michaela L.", "last_name": "Sundqvist", "name": null }, { "creator_type": "author", "first_name": "Xiaowei", "last_name": "Zheng", "name": null }, { "creator_type": "author", "first_name": "Tong", "last_name": "Jiao", "name": null }, { "creator_type": "author", "first_name": "Aida", "last_name": "Collado", "name": null }, { "creator_type": "author", "first_name": "Yahor", "last_name": "Tratsiakovich", "name": null }, { "creator_type": "author", "first_name": "Ali", "last_name": "Mahdi", "name": null }, { "creator_type": "author", "first_name": "John", "last_name": "Tengbom", "name": null }, { "creator_type": "author", "first_name": "Evanthia", "last_name": "Mergia", "name": null }, { "creator_type": "author", "first_name": "Sergiu-Bogdan", "last_name": "Catrina", "name": null }, { "creator_type": "author", "first_name": "Zhichao", "last_name": "Zhou", "name": null }, { "creator_type": "author", "first_name": "Mattias", "last_name": "Carlstrom", "name": null }, { "creator_type": "author", "first_name": "Takaaki", "last_name": "Akaike", "name": null }, { "creator_type": "author", "first_name": "Miriam M.", "last_name": "Cortese-Krott", "name": null }, { "creator_type": "author", "first_name": "Eddie", "last_name": "Weitzberg", "name": null }, { "creator_type": "author", "first_name": "Jon O.", "last_name": "Lundberg", "name": null }, { "creator_type": "author", "first_name": "John", "last_name": "Pernow", "name": null } ], "identifiers": { "doi": { "normalized": "10.1172/jci167693" }, "pmcid": { "normalized": "PMC10471167" }, "pmid": { "normalized": "37655658" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cardiotonic Agents", "descriptor_ui": "D002316", "major_topic": true }, { "descriptor": "Cyclic GMP", "descriptor_ui": "D006152", "major_topic": true }, { "descriptor": "Erythrocytes", "descriptor_ui": "D004912", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Hypoxia", "descriptor_ui": "D000860", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Myocytes, Cardiac", "descriptor_ui": "D032383", "major_topic": false }, { "descriptor": "Nitrates", "descriptor_ui": "D009566", "major_topic": false }, { "descriptor": "Nitric Oxide", "descriptor_ui": "D009569", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Soluble Guanylyl Cyclase", "descriptor_ui": "D000071756", "major_topic": true } ], "publication": { "conference_name": null, "date": "2023 Sep 1", "date_precision": "day", "issue": "17", "normalized_date": "2023-09-01", "pages": "", "proceedings_title": null, "publisher": "", "title": "The Journal of clinical investigation", "volume": "133", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Hypoxic erythrocytes mediate cardioprotection through activation of soluble guanylate cyclase and release of cyclic GMP.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Biological systems are inherently noisy; however, they produce highly stereotyped tissue morphology. Drosophila pupal wings show a highly stereotypic folding through uniform expansion and subsequent buckling of wing epithelium within a surrounding cuticle sac. The folding pattern produced by buckling is generally stochastic; it is thus unclear how buckling leads to stereotypic tissue folding of the wings. We found that the extracellular matrix (ECM) protein, Dumpy, guides the position and direction of buckling-induced folds. Dumpy anchors the wing epithelium to the overlying cuticle at specific tissue positions. Tissue-wide alterations of Dumpy deposition and degradation yielded different buckling patterns. In summary, we propose that spatiotemporal ECM remodeling shapes stereotyped tissue folding through dynamic interactions between the epithelium and its external structures.", "classifications": [ { "id": "JPMJCR2121", "label": "JPMJCR2121", "researcher": "Minako Ueda", "type": "grant" }, { "id": "Fujimoto", "label": "Group Fujimoto", "parent": "Ueda", "type": "group" }, { "id": "Ueda", "label": "Group Ueda", "parent": "Ueda", "type": "group" }, { "id": "Ueda", "label": "Team Ueda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Alice", "last_name": "Tsuboi", "name": null }, { "creator_type": "author", "first_name": "Koichi", "last_name": "Fujimoto", "name": null }, { "creator_type": "author", "first_name": "Takefumi", "last_name": "Kondo", "name": null } ], "identifiers": { "doi": { "normalized": "10.1126/sciadv.adh2154" }, "pmcid": { "normalized": null }, "pmid": { "normalized": null } }, "mesh": [], "publication": { "conference_name": null, "date": "2023-09", "date_precision": "month", "issue": "35", "normalized_date": "2023-09", "pages": "eadh2154", "proceedings_title": null, "publisher": "American Association for the Advancement of Science", "title": "Science Advances", "volume": "9", "year": 2023 }, "ssbd": { "database": [ "ssbd-database-000367" ], "repository": [ "ssbd-repos-000367" ] }, "title": "Spatiotemporal remodeling of extracellular matrix orients epithelial sheet folding", "url": "https://www.science.org/doi/10.1126/sciadv.adh2154", "zotero": { "item_type": "journalArticle" } }, { "abstract": "In mammals, pluripotent cells transit through a continuum of distinct molecular and functional states en route to initiating lineage specification. Capturing pluripotent stem cells (PSCs) mirroring in vivo pluripotent states provides accessible in vitro models to study the pluripotency program and mechanisms underlying lineage restriction. Here, we develop optimal culture conditions to derive and propagate post-implantation epiblast-derived PSCs (EpiSCs) in rats, a valuable model for biomedical research. We show that rat EpiSCs (rEpiSCs) can be reset toward the naive pluripotent state with exogenous Klf4, albeit not with the other five candidate genes (Nanog, Klf2, Esrrb, Tfcp2l1, and Tbx3) effective in mice. Finally, we demonstrate that rat EpiSCs retain competency to produce authentic primordial germ cell-like cells that undergo functional gametogenesis leading to the birth of viable offspring. Our findings in the rat model uncover principles underpinning pluripotency and germline competency across species.", "classifications": [ { "id": "Yamamoto", "label": "Group Yamamoto", "parent": "Toyoshima", "type": "group" }, { "id": "Toyoshima", "label": "Team Toyoshima", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Kenyu", "last_name": "Iwatsuki", "name": null }, { "creator_type": "author", "first_name": "Mami", "last_name": "Oikawa", "name": null }, { "creator_type": "author", "first_name": "Hisato", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Christopher A.", "last_name": "Penfold", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Sanbo", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Shinichi", "last_name": "Hochi", "name": null }, { "creator_type": "author", "first_name": "Kazuki", "last_name": "Kurimoto", "name": null }, { "creator_type": "author", "first_name": "Masumi", "last_name": "Hirabayashi", "name": null }, { "creator_type": "author", "first_name": "Toshihiro", "last_name": "Kobayashi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.crmeth.2023.100542" }, "pmcid": { "normalized": "PMC10475792" }, "pmid": { "normalized": "37671016" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Biomedical Research", "descriptor_ui": "D035843", "major_topic": true }, { "descriptor": "Embryo Implantation", "descriptor_ui": "D010064", "major_topic": false }, { "descriptor": "Germ Cells", "descriptor_ui": "D005854", "major_topic": false }, { "descriptor": "Germ Layers", "descriptor_ui": "D005855", "major_topic": false }, { "descriptor": "Kruppel-Like Transcription Factors", "descriptor_ui": "D051741", "major_topic": false }, { "descriptor": "Mammals", "descriptor_ui": "D008322", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Pluripotent Stem Cells", "descriptor_ui": "D039904", "major_topic": true }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false } ], "publication": { "conference_name": null, "date": "2023 Aug 28", "date_precision": "day", "issue": "8", "normalized_date": "2023-08-28", "pages": "100542", "proceedings_title": null, "publisher": "", "title": "Cell reports methods", "volume": "3", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Rat post-implantation epiblast-derived pluripotent stem cells produce functional germ cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Histidine (His) residues are methylated in various proteins, but their roles and regulation mechanisms remain unknown. Here, we show that carnosine N-methyltransferase 1 (CARNMT1), a known His methyltransferase of dipeptide carnosine (betaAla-His), is a major His N1-position-specific methyltransferase. We found that 52 His sites in 20 proteins underwent CARNMT1-mediated methylation. The consensus methylation site for CARNMT1 was identified as Cx(F/Y)xH, a C3H zinc finger (C3H ZF) motif. CARNMT1-deficient and catalytically inactive mutant mice showed embryonic lethality. Among the CARNMT1 target C3H ZF proteins, RNA degradation mediated by Roquin and tristetraprolin (TTP) was affected by CARNMT1 and its enzymatic activity. Furthermore, the recognition of the 3' splice site of the CARNMT1 target C3H ZF protein U2AF1 was perturbed, and pre-mRNA alternative splicing (AS) was affected by CARNMT1 deficiency. These findings indicate that CARNMT1-mediated protein His methylation, which is essential for embryogenesis, plays roles in diverse aspects of RNA metabolism by targeting C3H ZF-type RNA-binding proteins and modulating their functions, including pre-mRNA AS and mRNA degradation regulation.", "classifications": [ { "id": "Sodeoka", "label": "Group Sodeoka", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Tadahiro", "last_name": "Shimazu", "name": null }, { "creator_type": "author", "first_name": "Rei", "last_name": "Yoshimoto", "name": null }, { "creator_type": "author", "first_name": "Kaoru", "last_name": "Kotoshiba", "name": null }, { "creator_type": "author", "first_name": "Takehiro", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Shogo", "last_name": "Matoba", "name": null }, { "creator_type": "author", "first_name": "Michiko", "last_name": "Hirose", "name": null }, { "creator_type": "author", "first_name": "Mai", "last_name": "Akakabe", "name": null }, { "creator_type": "author", "first_name": "Yoshihiro", "last_name": "Sohtome", "name": null }, { "creator_type": "author", "first_name": "Mikiko", "last_name": "Sodeoka", "name": null }, { "creator_type": "author", "first_name": "Atsuo", "last_name": "Ogura", "name": null }, { "creator_type": "author", "first_name": "Naoshi", "last_name": "Dohmae", "name": null }, { "creator_type": "author", "first_name": "Yoichi", "last_name": "Shinkai", "name": null } ], "identifiers": { "doi": { "normalized": "10.1101/gad.350755.123" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "37612136" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Carnosine", "descriptor_ui": "D002336", "major_topic": true }, { "descriptor": "Histidine", "descriptor_ui": "D006639", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C3H", "descriptor_ui": "D008809", "major_topic": false }, { "descriptor": "Protein Methyltransferases", "descriptor_ui": "D011496", "major_topic": true }, { "descriptor": "RNA Precursors", "descriptor_ui": "D012322", "major_topic": false }, { "descriptor": "RNA Splice Sites", "descriptor_ui": "D022821", "major_topic": false }, { "descriptor": "Zinc Fingers", "descriptor_ui": "D016335", "major_topic": false } ], "publication": { "conference_name": null, "date": "2023 Aug 23", "date_precision": "day", "issue": "", "normalized_date": "2023-08-23", "pages": "", "proceedings_title": null, "publisher": "", "title": "Genes & development", "volume": "", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Histidine N1-position-specific methyltransferase CARNMT1 targets C3H zinc finger proteins and modulates RNA metabolism.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Abstract Nanog and Oct4 are core transcription factors that form part of a gene regulatory network to regulate hundreds of target genes for pluripotency maintenance in mouse embryonic stem cells (ESCs). To understand their function in the pluripotency maintenance, we visualised and quantified the dynamics of single molecules of Nanog and Oct4 in a mouse ESCs during pluripotency loss. Interestingly, Nanog interacted longer with its target loci upon reduced expression or at the onset of differentiation, suggesting a feedback mechanism to maintain the pluripotent state. The expression level and interaction time of Nanog and Oct4 correlate with their fluctuation and interaction frequency, respectively, which in turn depend on the ESC differentiation status. The DNA viscoelasticity near the Oct4 target locus remained flexible during differentiation, supporting its role either in chromatin opening or a preferred binding to uncondensed chromatin regions. Based on these results, we propose a new negative feedback mechanism for pluripotency maintenance via the DNA condensation state-dependent interplay of Nanog and Oct4.", "classifications": [ { "id": "Onami", "label": "Group Onami", "parent": "Fujiwara", "type": "group" }, { "id": "Fujiwara", "label": "Team Fujiwara", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Kazuko", "last_name": "Okamoto", "name": null }, { "creator_type": "author", "first_name": "Hideaki", "last_name": "Fujita", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Okada", "name": null }, { "creator_type": "author", "first_name": "Soya", "last_name": "Shinkai", "name": null }, { "creator_type": "author", "first_name": "Shuichi", "last_name": "Onami", "name": null }, { "creator_type": "author", "first_name": "Kuniya", "last_name": "Abe", "name": null }, { "creator_type": "author", "first_name": "Kenta", "last_name": "Fujimoto", "name": null }, { "creator_type": "author", "first_name": "Kensuke", "last_name": "Sasaki", "name": null }, { "creator_type": "author", "first_name": "Go", "last_name": "Shioi", "name": null }, { "creator_type": "author", "first_name": "Tomonobu M", "last_name": "Watanabe", "name": null } ], "identifiers": { "doi": { "normalized": "10.15252/embj.2022112305" }, "pmcid": { "normalized": null }, "pmid": { "normalized": null } }, "mesh": [], "publication": { "conference_name": null, "date": "2023-08-23", "date_precision": "day", "issue": "n/a", "normalized_date": "2023-08-23", "pages": "e112305", "proceedings_title": null, "publisher": "John Wiley & Sons, Ltd", "title": "The EMBO Journal", "volume": "n/a", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Single-molecule tracking of Nanog and Oct4 in living mouse embryonic stem cells uncovers a feedback mechanism of pluripotency maintenance", "url": "https://www.embopress.org/doi/full/10.15252/embj.2022112305", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: Clinical trials have reported the efficacy of immune checkpoint inhibitors in the treatment of mismatch repair-deficient (dMMR) advanced solid tumors. The accumulated evidence of tumor agnostic agent has been made since PD-1 inhibitor was approved and used in clinical practice. Therefore, we have revised the guideline \"Japan Society of Clinical Oncology provisional clinical opinion for the diagnosis and use of immunotherapy in patients with deficient DNA mismatch repair tumors, cooperated by Japanese Society of Medical Oncology, First Edition\". METHODS: Clinical questions regarding medical care were formulated for patients with dMMR advanced solid tumors. Relevant publications were searched by PubMed and Cochrane Database. Critical publications and conference reports were added manually. Systematic reviews were performed for each clinical question for the purpose of developing clinical recommendations. The committee members identified by Japan Society of Clinical Oncology (JSCO), Japanese Society of Medical Oncology (JSMO), and Japanese society of pediatric hematology/oncology (JSPHO) voted to determine the level of each recommendation considering the strength of evidence, expected risks and benefits to patients, and other related factors. Thereafter, a peer review by experts nominated from JSCO, JSMO, and JSPHO and the public comments among all societies' members were done. RESULTS: The current guideline describes two clinical questions and eight recommendations for whom, when, and how MMR status should be tested. CONCLUSION: In this guideline, the committee proposed eight recommendations for performing MMR testing properly to select patients who are likely to benefit from immunotherapy.", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Saori", "last_name": "Mishima", "name": null }, { "creator_type": "author", "first_name": "Yoichi", "last_name": "Naito", "name": null }, { "creator_type": "author", "first_name": "Kiwamu", "last_name": "Akagi", "name": null }, { "creator_type": "author", "first_name": "Naomi", "last_name": "Hayashi", "name": null }, { "creator_type": "author", "first_name": "Akira", "last_name": "Hirasawa", "name": null }, { "creator_type": "author", "first_name": "Tomoro", "last_name": "Hishiki", "name": null }, { "creator_type": "author", "first_name": "Ataru", "last_name": "Igarashi", "name": null }, { "creator_type": "author", "first_name": "Masafumi", "last_name": "Ikeda", "name": null }, { "creator_type": "author", "first_name": "Shigenori", "last_name": "Kadowaki", "name": null }, { "creator_type": "author", "first_name": "Hiroaki", "last_name": "Kajiyama", "name": null }, { "creator_type": "author", "first_name": "Motohiro", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Hirotsugu", "last_name": "Kenmotsu", "name": null }, { "creator_type": "author", "first_name": "Yasuhiro", "last_name": "Kodera", "name": null }, { "creator_type": "author", "first_name": "Keigo", "last_name": "Komine", "name": null }, { "creator_type": "author", "first_name": "Takafumi", "last_name": "Koyama", "name": null }, { "creator_type": "author", "first_name": "Osamu", "last_name": "Maeda", "name": null }, { "creator_type": "author", "first_name": "Mitsuru", "last_name": "Miyachi", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Nishihara", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Nishiyama", "name": null }, { "creator_type": "author", "first_name": "Shouichi", "last_name": "Ohga", "name": null }, { "creator_type": "author", "first_name": "Wataru", "last_name": "Okamoto", "name": null }, { "creator_type": "author", "first_name": "Eiji", "last_name": "Oki", "name": null }, { "creator_type": "author", "first_name": "Shigeru", "last_name": "Ono", "name": null }, { "creator_type": "author", "first_name": "Masashi", "last_name": "Sanada", "name": null }, { "creator_type": "author", "first_name": "Ikuo", "last_name": "Sekine", "name": null }, { "creator_type": "author", "first_name": "Tadao", "last_name": "Takano", "name": null }, { "creator_type": "author", "first_name": "Kayoko", "last_name": "Tao", "name": null }, { "creator_type": "author", "first_name": "Keita", "last_name": "Terashima", "name": null }, { "creator_type": "author", "first_name": "Katsuya", "last_name": "Tsuchihara", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null }, { "creator_type": "author", "first_name": "Takayuki", "last_name": "Yoshino", "name": null }, { "creator_type": "author", "first_name": "Eishi", "last_name": "Baba", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/s10147-023-02397-9" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "37599324" } }, "mesh": [ { "descriptor": "Colorectal Neoplasms", "descriptor_ui": "D015179", "major_topic": true }, { "descriptor": "DNA Mismatch Repair", "descriptor_ui": "D053843", "major_topic": false }, { "descriptor": "Hematology", "descriptor_ui": "D006405", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Immunotherapy", "descriptor_ui": "D007167", "major_topic": false }, { "descriptor": "Japan", "descriptor_ui": "D007564", "major_topic": false }, { "descriptor": "Medical Oncology", "descriptor_ui": "D008495", "major_topic": false }, { "descriptor": "Neoplasms", "descriptor_ui": "D009369", "major_topic": true } ], "publication": { "conference_name": null, "date": "2023 Aug 20", "date_precision": "day", "issue": "", "normalized_date": "2023-08-20", "pages": "", "proceedings_title": null, "publisher": "", "title": "International journal of clinical oncology", "volume": "", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Japanese Society of Medical Oncology/Japan Society of Clinical Oncology/Japanese Society of Pediatric Hematology/Oncology-led clinical recommendations on the diagnosis and use of immunotherapy in patients with DNA mismatch repair deficient (dMMR) tumors, third edition.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "ACTIN DEPOLYMERIZING FACTOR (ADF) is a conserved protein that regulates the organization and dynamics of actin microfilaments. Eleven ADFs in the Arabidopsis thaliana genome are grouped into four subclasses, and subclass I ADFs, ADF1-4, are all expressed throughout the plant. Previously, we showed that subclass I ADFs function in the regulation of the response against powdery mildew fungus as well as in the regulation of cell size and endoreplication. Here, we report a new role of subclass I ADFs in the regulation of nuclear organization and gene expression. Through microscopic observation of epidermal cells in mature leaves, we found that the size of chromocenters in both adf4 and transgenic lines where expression of subclass I ADFs is downregulated (ADF1-4Ri) was reduced compared with that of wild-type Col-0. Arabidopsis thaliana possesses eight ACTIN (ACT) genes, among which ACT2, -7 and -8 are expressed in vegetative organs. The chromocenter size in act7, but not in the act2/8 double mutant, was enlarged compared with that in Col-0. Microarray analysis revealed that 1,818 genes were differentially expressed in adf4 and ADF1-4Ri. In particular, expression of 22 nucleotide-binding leucine-rich repeat genes, which are involved in effector-triggered plant immunity, was reduced in adf4 and ADF1-4Ri. qRT-PCR confirmed the altered expressions shown with microarray analysis. Overall, these results suggest that ADF regulates various aspects of plant physiology through its role in regulation of nuclear organization and gene expression. The mechanism how ADF and ACT regulate nuclear organization and gene expression is discussed.", "classifications": [ { "id": "Higaki", "label": "Group Higaki", "parent": "Ueda", "type": "group" }, { "id": "Ueda", "label": "Team Ueda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Tomoko", "last_name": "Matsumoto", "name": null }, { "creator_type": "author", "first_name": "Takumi", "last_name": "Higaki", "name": null }, { "creator_type": "author", "first_name": "Hirotomo", "last_name": "Takatsuka", "name": null }, { "creator_type": "author", "first_name": "Natsumaro", "last_name": "Kutsuna", "name": null }, { "creator_type": "author", "first_name": "Yoshiyuki", "last_name": "Ogata", "name": null }, { "creator_type": "author", "first_name": "Seiichiro", "last_name": "Hasezawa", "name": null }, { "creator_type": "author", "first_name": "Masaaki", "last_name": "Umeda", "name": null }, { "creator_type": "author", "first_name": "Noriko", "last_name": "Inada", "name": null } ], "identifiers": { "doi": { "normalized": "10.1093/pcp/pcad092" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "37647615" } }, "mesh": [ { "descriptor": "Actin Depolymerizing Factors", "descriptor_ui": "D051339", "major_topic": true }, { "descriptor": "Arabidopsis", "descriptor_ui": "D017360", "major_topic": true }, { "descriptor": "Arabidopsis Proteins", "descriptor_ui": "D029681", "major_topic": true }, { "descriptor": "Cell Nucleus", "descriptor_ui": "D002467", "major_topic": true }, { "descriptor": "Gene Expression Regulation, Plant", "descriptor_ui": "D018506", "major_topic": true }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": false }, { "descriptor": "Plant Leaves", "descriptor_ui": "D018515", "major_topic": false }, { "descriptor": "Plants, Genetically Modified", "descriptor_ui": "D030821", "major_topic": false } ], "publication": { "conference_name": null, "date": "2023 Aug 18", "date_precision": "day", "issue": "", "normalized_date": "2023-08-18", "pages": "pcad092", "proceedings_title": null, "publisher": "", "title": "Plant & cell physiology", "volume": "", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Arabidopsis thaliana Subclass I ACTIN DEPOLYMERIZING FACTORs Regulate Nuclear Organization and Gene Expression.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Abundant formation of endogenous supersulfides, which include reactive persulfide species and sulfur catenated residues in thiols and proteins (supersulfidation), has been observed. We found here that supersulfides catalyze S-nitrosoglutathione (GSNO) metabolism via glutathione-dependent electron transfer from aldehydes by exploiting alcohol dehydrogenase 5 (ADH5). ADH5 is a highly conserved bifunctional enzyme serving as GSNO reductase (GSNOR) that down-regulates NO signaling and formaldehyde dehydrogenase (FDH) that detoxifies formaldehyde in the form of glutathione hemithioacetal. C174S mutation significantly reduced the supersulfidation of ADH5 and almost abolished GSNOR activity but spared FDH activity. Notably, Adh5C174S/C174S mice manifested improved cardiac functions possibly because of GSNOR elimination and consequent increased NO bioavailability. Therefore, we successfully separated dual functions (GSNOR and FDH) of ADH5 (mediated by the supersulfide catalysis) through the biochemical analysis for supersulfides in vitro and characterizing in vivo phenotypes of the GSNOR-deficient organisms that we established herein. Supersulfides in ADH5 thus constitute a substantial catalytic center for GSNO metabolism mediating electron transfer from aldehydes.", "classifications": [ { "id": "JPMJCR2024", "label": "JPMJCR2024", "researcher": "Motohiro Nishida", "type": "grant" }, { "id": "Nishida", "label": "Group Nishida", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Shingo", "last_name": "Kasamatsu", "name": null }, { "creator_type": "author", "first_name": "Akira", "last_name": "Nishimura", "name": null }, { "creator_type": "author", "first_name": "Md. Morshedul", "last_name": "Alam", "name": null }, { "creator_type": "author", "first_name": "Masanobu", "last_name": "Morita", "name": null }, { "creator_type": "author", "first_name": "Kakeru", "last_name": "Shimoda", "name": null }, { "creator_type": "author", "first_name": "Tetsuro", "last_name": "Matsunaga", "name": null }, { "creator_type": "author", "first_name": "Minkyung", "last_name": "Jung", "name": null }, { "creator_type": "author", "first_name": "Seiryo", "last_name": "Ogata", "name": null }, { "creator_type": "author", "first_name": "Uladzimir", "last_name": "Barayeu", "name": null }, { "creator_type": "author", "first_name": "Tomoaki", "last_name": "Ida", "name": null }, { "creator_type": "author", "first_name": "Motohiro", "last_name": "Nishida", "name": null }, { "creator_type": "author", "first_name": "Akiyuki", "last_name": "Nishimura", "name": null }, { "creator_type": "author", "first_name": "Hozumi", "last_name": "Motohashi", "name": null }, { "creator_type": "author", "first_name": "Takaaki", "last_name": "Akaike", "name": null } ], "identifiers": { "doi": { "normalized": "10.1126/sciadv.adg8631" }, "pmcid": { "normalized": null }, "pmid": { "normalized": null } }, "mesh": [], "publication": { "conference_name": null, "date": "2023-08-18", "date_precision": "day", "issue": "33", "normalized_date": "2023-08-18", "pages": "eadg8631", "proceedings_title": null, "publisher": "American Association for the Advancement of Science", "title": "Science Advances", "volume": "9", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Supersulfide catalysis for nitric oxide and aldehyde metabolism", "url": "https://www.science.org/doi/10.1126/sciadv.adg8631", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Activation of the KRAS oncogene is a source of replication stress, but how this stress is generated and how it is tolerated by cancer cells remain poorly understood. Here we show that induction of KRAS(G12V) expression in untransformed cells triggers H3K27me3 and HP1-associated chromatin compaction in an RNA transcription dependent manner, resulting in replication fork slowing and cell death. Furthermore, elevated ATR expression is necessary and sufficient for tolerance of KRAS(G12V)-induced replication stress to expand replication stress-tolerant cells (RSTCs). PrimPol is phosphorylated at Ser255, a potential Chk1 substrate site, under KRAS(G12V)-induced replication stress and promotes repriming to maintain fork progression and cell survival in an ATR/Chk1-dependent manner. However, ssDNA gaps are generated at heterochromatin by PrimPol-dependent repriming, leading to genomic instability. These results reveal a role of ATR-PrimPol in enabling precancerous cells to survive KRAS-induced replication stress and expand clonally with accumulation of genomic instability.", "classifications": [ { "id": "Hamamoto", "label": "Group Hamamoto", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Taichi", "last_name": "Igarashi", "name": null }, { "creator_type": "author", "first_name": "Marianne", "last_name": "Mazevet", "name": null }, { "creator_type": "author", "first_name": "Takaaki", "last_name": "Yasuhara", "name": null }, { "creator_type": "author", "first_name": "Kimiyoshi", "last_name": "Yano", "name": null }, { "creator_type": "author", "first_name": "Akifumi", "last_name": "Mochizuki", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Nishino", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Yukihiro", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Nobuhiko", "last_name": "Takamatsu", "name": null }, { "creator_type": "author", "first_name": "Akihide", "last_name": "Yoshimi", "name": null }, { "creator_type": "author", "first_name": "Kouya", "last_name": "Shiraishi", "name": null }, { "creator_type": "author", "first_name": "Hidehito", "last_name": "Horinouchi", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Kohno", "name": null }, { "creator_type": "author", "first_name": "Ryuji", "last_name": "Hamamoto", "name": null }, { "creator_type": "author", "first_name": "Jun", "last_name": "Adachi", "name": null }, { "creator_type": "author", "first_name": "Lee", "last_name": "Zou", "name": null }, { "creator_type": "author", "first_name": "Bunsyo", "last_name": "Shiotani", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41467-023-40578-2" }, "pmcid": { "normalized": "PMC10435487" }, "pmid": { "normalized": "37591859" } }, "mesh": [ { "descriptor": "Ataxia Telangiectasia Mutated Proteins", "descriptor_ui": "D064007", "major_topic": false }, { "descriptor": "Chromatin", "descriptor_ui": "D002843", "major_topic": false }, { "descriptor": "DNA Primase", "descriptor_ui": "D019915", "major_topic": false }, { "descriptor": "DNA-Directed DNA Polymerase", "descriptor_ui": "D004259", "major_topic": false }, { "descriptor": "Genomic Instability", "descriptor_ui": "D042822", "major_topic": false }, { "descriptor": "Heterochromatin", "descriptor_ui": "D006570", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Multifunctional Enzymes", "descriptor_ui": "D064251", "major_topic": false }, { "descriptor": "Proto-Oncogene Proteins p21(ras)", "descriptor_ui": "D016283", "major_topic": true } ], "publication": { "conference_name": null, "date": "2023 Aug 17", "date_precision": "day", "issue": "1", "normalized_date": "2023-08-17", "pages": "4991", "proceedings_title": null, "publisher": "", "title": "Nature communications", "volume": "14", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "An ATR-PrimPol pathway confers tolerance to oncogenic KRAS-induced and heterochromatin-associated replication stress.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Graft failure and delayed hematopoietic recovery are the major limitations of cord-blood transplantation (CBT). Romiplostim, a thrombopoietin-receptor agonist, promotes megakaryopoiesis and multilineage hematopoiesis in aplastic anemia. The decreased number of hematopoietic stem cells in the early phase after CBT and aplastic anemia share certain characteristics. Therefore, we hypothesized that romiplostim administration immediately after CBT may promote multilineage hematopoietic recovery. We investigated the safety and preliminary efficacy of administering romiplostim a day after CBT. This phase 1 dose-escalation study included six adults with hematologic malignancies in remission. Romiplostim was administered subcutaneously within 7 days after single-unit CBT, initially at doses of 5 microg/kg or 10 microg/kg in three patients, then once a week for 14 weeks or until platelet recovery. The maximum dose was 20 microg/kg. The median number of romiplostim administrations was 6 (range, 3-15). Romiplostim-related adverse events included bone pain (3/6) and injection site reaction (1/6). Non-hematological grade >/= 3 toxicities were observed in four patients; febrile neutropenia was the most common (4/6). All patients achieved neutrophil engraftment and the median time was 14 days (range, 12-32). Platelet counts >/= 50 x 10(9) /L were recorded in all patients except for one who died on day 48; the median time was 34 days (range, 29-98). No relapse, thrombosis, or bone marrow fibrosis was observed during a median follow-up of 34 months. Romiplostim may be safely administered in the early phase of CBT. Further phase 2 trial is warranted for its efficacy evaluation. Trial registration number: UMIN000033799, August 18, 2018.", "classifications": [ { "id": "Nishikii", "label": "Group Nishikii", "parent": "Shintaku", "type": "group" }, { "id": "Shintaku", "label": "Team Shintaku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Naoki", "last_name": "Kurita", "name": null }, { "creator_type": "author", "first_name": "Hidekazu", "last_name": "Nishikii", "name": null }, { "creator_type": "author", "first_name": "Yumiko", "last_name": "Maruyama", "name": null }, { "creator_type": "author", "first_name": "Yasuhito", "last_name": "Suehara", "name": null }, { "creator_type": "author", "first_name": "Keiichiro", "last_name": "Hattori", "name": null }, { "creator_type": "author", "first_name": "Tatsuhiro", "last_name": "Sakamoto", "name": null }, { "creator_type": "author", "first_name": "Takayasu", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Yasuhisa", "last_name": "Yokoyama", "name": null }, { "creator_type": "author", "first_name": "Naoshi", "last_name": "Obara", "name": null }, { "creator_type": "author", "first_name": "Kazushi", "last_name": "Maruo", "name": null }, { "creator_type": "author", "first_name": "Tomohiro", "last_name": "Ohigashi", "name": null }, { "creator_type": "author", "first_name": "Hitomi", "last_name": "Yamaguchi", "name": null }, { "creator_type": "author", "first_name": "Toshiro", "last_name": "Iwamoto", "name": null }, { "creator_type": "author", "first_name": "Hideto", "last_name": "Minohara", "name": null }, { "creator_type": "author", "first_name": "Ryota", "last_name": "Matsuoka", "name": null }, { "creator_type": "author", "first_name": "Koichi", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Mamiko", "last_name": "Sakata-Yanagimoto", "name": null }, { "creator_type": "author", "first_name": "Shigeru", "last_name": "Chiba", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/s00277-023-05410-3" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "37589942" } }, "mesh": [ { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Anemia, Aplastic", "descriptor_ui": "D000741", "major_topic": true }, { "descriptor": "Hematopoietic Stem Cell Transplantation", "descriptor_ui": "D018380", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Neoplasm Recurrence, Local", "descriptor_ui": "D009364", "major_topic": false }, { "descriptor": "Receptors, Fc", "descriptor_ui": "D011961", "major_topic": false }, { "descriptor": "Recombinant Fusion Proteins", "descriptor_ui": "D011993", "major_topic": false }, { "descriptor": "Thrombopoietin", "descriptor_ui": "D013926", "major_topic": false } ], "publication": { "conference_name": null, "date": "2023 Aug 17", "date_precision": "day", "issue": "", "normalized_date": "2023-08-17", "pages": "", "proceedings_title": null, "publisher": "", "title": "Annals of hematology", "volume": "", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Safety of romiplostim administered immediately after cord-blood transplantation: a phase 1 trial.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "SIGNIFICANCE: Persulfides/polysulfides are sulfur-catenated molecular species (i.e., R-S(n)-R', n > 2; R-S(n)-H, n > 1, with R = cysteine, glutathione, and proteins), such as cysteine persulfide (CysSSH). These species are abundantly formed as endogenous metabolites in mammalian and human cells and tissues. However, the persulfide synthesis mechanism has yet to be thoroughly discussed. RECENT ADVANCES: We used beta-(4-hydroxyphenyl)ethyl iodoacetamide and mass spectrometry to develop sulfur metabolomics, a highly precise, quantitative analytical method for sulfur metabolites. CRITICAL ISSUES: With this method, we detected appreciable amounts of different persulfide species in biological specimens from various organisms, from the domains Bacteria, Archaea, and Eukarya. By using our rigorously quantitative approach, we identified cysteinyl-tRNA synthetase (CARS) as a novel persulfide synthase, and we found that the CysSSH synthase activity of CARS is highly conserved from the domains Bacteria to Eukarya. Because persulfide synthesis is found not only with CARS but also with other sulfotransferase enzymes in many organisms, persulfides/polysulfides are expected to contribute as fundamental elements to substantially diverse biological phenomena. In fact, persulfide generation in higher organisms-i.e., plants and animals-demonstrated various physiological functions that are mediated by redox signaling, such as regulation of energy metabolism, infection, inflammation, and cell death including ferroptosis. FUTURE DIRECTIONS: Investigating CARS-dependent persulfide production may clarify various pathways of redox signaling in physiological and pathophysiological conditions and may thereby promote the development of preventive and therapeutic measures for oxidative stress as well as different inflammatory, metabolic, and neurodegenerative diseases.", "classifications": [ { "id": "JPMJCR2024", "label": "JPMJCR2024", "researcher": "Motohiro Nishida", "type": "grant" }, { "id": "Akaike", "label": "Group Akaike", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Group Nishida", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Seiryo", "last_name": "Ogata", "name": null }, { "creator_type": "author", "first_name": "Tetsuro", "last_name": "Matsunaga", "name": null }, { "creator_type": "author", "first_name": "Minkyung", "last_name": "Jung", "name": null }, { "creator_type": "author", "first_name": "Uladzimir", "last_name": "Barayeu", "name": null }, { "creator_type": "author", "first_name": "Masanobu", "last_name": "Morita", "name": null }, { "creator_type": "author", "first_name": "Takaaki", "last_name": "Akaike", "name": null } ], "identifiers": { "doi": { "normalized": "10.1089/ars.2023.0405" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "37565274" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cysteine", "descriptor_ui": "D003545", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mammals", "descriptor_ui": "D008322", "major_topic": false }, { "descriptor": "Oxidation-Reduction", "descriptor_ui": "D010084", "major_topic": false }, { "descriptor": "Sulfides", "descriptor_ui": "D013440", "major_topic": true }, { "descriptor": "Sulfur", "descriptor_ui": "D013455", "major_topic": false } ], "publication": { "conference_name": null, "date": "2023 Aug 11", "date_precision": "day", "issue": "", "normalized_date": "2023-08-11", "pages": "", "proceedings_title": null, "publisher": "", "title": "Antioxidants & redox signaling", "volume": "", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Persulfide Biosynthesis Conserved Evolutionarily in All Organisms.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Organisms have evolved under gravitational force and many sense the direction of gravity via statoliths in specialized cells. In flowering plants, starch-accumulating plastids, known as amyloplasts, act as statoliths to facilitate downstream gravitropism. The gravity sensing mechanism has long been considered a mechanosensing process by which amyloplasts transmit forces to intracellular structures, but the molecular mechanism underlying this has not been elucidated. We show here that LAZY1-LIKE (LZY) family proteins involved in statocyte gravity signaling associate with amyloplasts and its proximal plasma membrane. This results in polar localization according to the direction of gravity. We propose a gravity sensing mechanism by which LZY translocation to the plasma membrane signals the direction of gravity by transmitting information on the position of amyloplasts.", "classifications": [ { "id": "Higaki", "label": "Group Higaki", "parent": "Ueda", "type": "group" }, { "id": "Ueda", "label": "Team Ueda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Takeshi", "last_name": "Nishimura", "name": null }, { "creator_type": "author", "first_name": "Shogo", "last_name": "Mori", "name": null }, { "creator_type": "author", "first_name": "Hiromasa", "last_name": "Shikata", "name": null }, { "creator_type": "author", "first_name": "Moritaka", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Yasuko", "last_name": "Hashiguchi", "name": null }, { "creator_type": "author", "first_name": "Yoshinori", "last_name": "Abe", "name": null }, { "creator_type": "author", "first_name": "Takuma", "last_name": "Hagihara", "name": null }, { "creator_type": "author", "first_name": "Hiroshi Y.", "last_name": "Yoshikawa", "name": null }, { "creator_type": "author", "first_name": "Masatsugu", "last_name": "Toyota", "name": null }, { "creator_type": "author", "first_name": "Takumi", "last_name": "Higaki", "name": null }, { "creator_type": "author", "first_name": "Miyo Terao", "last_name": "Morita", "name": null } ], "identifiers": { "doi": { "normalized": "10.1126/science.adh9978" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "37561884" } }, "mesh": [ { "descriptor": "Arabidopsis", "descriptor_ui": "D017360", "major_topic": true }, { "descriptor": "Arabidopsis Proteins", "descriptor_ui": "D029681", "major_topic": true }, { "descriptor": "Cell Membrane", "descriptor_ui": "D002462", "major_topic": true }, { "descriptor": "Cell Polarity", "descriptor_ui": "D016764", "major_topic": true }, { "descriptor": "Gravitation", "descriptor_ui": "D006112", "major_topic": false }, { "descriptor": "Gravitropism", "descriptor_ui": "D018522", "major_topic": true }, { "descriptor": "Gravity Sensing", "descriptor_ui": "D018466", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Plastids", "descriptor_ui": "D018087", "major_topic": true }, { "descriptor": "Protein Transport", "descriptor_ui": "D021381", "major_topic": false } ], "publication": { "conference_name": null, "date": "2023 Aug 10", "date_precision": "day", "issue": "", "normalized_date": "2023-08-10", "pages": "eadh9978", "proceedings_title": null, "publisher": "", "title": "Science (New York, N.Y.)", "volume": "", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Cell polarity linked to gravity sensing is generated by LZY translocation from statoliths to the plasma membrane.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Raman hyperspectral microscopy is a valuable tool in biological and biomedical imaging. Because Raman scattering is often weak in comparison to other phenomena, prevalent spectral fluctuations and contaminations have brought advancements in analytical and chemometric methods for Raman spectra. These chemometric advances have been key contributors to the applicability of Raman imaging to biological systems. As studies increase in scale, spectral contamination from extrinsic background, intensity from sources such as the optical components that are extrinsic to the sample of interest, has become an emerging issue. Although existing baseline correction schemes often reduce intrinsic background such as autofluorescence originating from the sample of interest, extrinsic background is not explicitly considered, and these methods often fail to reduce its effects. Here, we show that extrinsic background can significantly affect a classification model using Raman images, yielding misleadingly high accuracies in the distinction of benign and malignant samples of follicular thyroid cell lines. To mitigate its effects, we develop extrinsic background correction (EBC) and demonstrate its use in combination with existing methods on Raman hyperspectral images. EBC isolates regions containing the smallest amounts of sample materials that retain extrinsic contributions that are specific to the device or environment. We perform classification both with and without the use of EBC, and we find that EBC retains biological characteristics in the spectra while significantly reducing extrinsic background. As the methodology used in EBC is not specific to Raman spectra, correction of extrinsic effects in other types of hyperspectral and grayscale images is also possible.", "classifications": [ { "id": "Fujita", "label": "Group Fujita", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "J. Nicholas", "last_name": "Taylor", "name": null }, { "creator_type": "author", "first_name": "Aurelien", "last_name": "Pelissier", "name": null }, { "creator_type": "author", "first_name": "Kentaro", "last_name": "Mochizuki", "name": null }, { "creator_type": "author", "first_name": "Kosuke", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Yasuaki", "last_name": "Kumamoto", "name": null }, { "creator_type": "author", "first_name": "Yoshinori", "last_name": "Harada", "name": null }, { "creator_type": "author", "first_name": "Katsumasa", "last_name": "Fujita", "name": null }, { "creator_type": "author", "first_name": "Thomas", "last_name": "Bocklitz", "name": null }, { "creator_type": "author", "first_name": "Tamiki", "last_name": "Komatsuzaki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/acs.analchem.3c01406" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "37561910" } }, "mesh": [], "publication": { "conference_name": null, "date": "2023 Aug 10", "date_precision": "day", "issue": "", "normalized_date": "2023-08-10", "pages": "", "proceedings_title": null, "publisher": "", "title": "Analytical chemistry", "volume": "", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Correction for Extrinsic Background in Raman Hyperspectral Images.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Palladium enolates derived from beta-ketocarbonyl compounds serve as key intermediates in various catalytic asymmetric reactions. We found that the palladium enolate formed from beta-ketoamide is stable in air and moisture and we applied this property to develop a peptide purification system using beta-ketoamide as a small affinity tag in aqueous media. A solid-supported palladium complex successfully captured beta-ketoamide-tagged molecules as palladium enolates and released them in high yield upon acid treatment. Optimum conditions for the catch and release of tagged peptides from a mixture of untagged peptides were established. To demonstrate the value of this methodology in identifying the binding site of a ligand to its target protein, we purified and identified a peptide containing the ligand-binding site from the tryptic digest of cathepsin B labelled with a covalent cathepsin B inhibitor containing a beta-ketoamide tag.", "classifications": [ { "id": "Sodeoka", "label": "Group Sodeoka", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Kenji", "last_name": "Hayamizu", "name": null }, { "creator_type": "author", "first_name": "Kota", "last_name": "Koike", "name": null }, { "creator_type": "author", "first_name": "Kosuke", "last_name": "Dodo", "name": null }, { "creator_type": "author", "first_name": "Miwako", "last_name": "Asanuma", "name": null }, { "creator_type": "author", "first_name": "Hiromichi", "last_name": "Egami", "name": null }, { "creator_type": "author", "first_name": "Mikiko", "last_name": "Sodeoka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1039/d2sc03112d" }, "pmcid": { "normalized": "PMC10411859" }, "pmid": { "normalized": "37564408" } }, "mesh": [], "publication": { "conference_name": null, "date": "2023 Aug 9", "date_precision": "day", "issue": "31", "normalized_date": "2023-08-09", "pages": "8249-8254", "proceedings_title": null, "publisher": "", "title": "Chemical science", "volume": "14", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Simple purification of small-molecule-labelled peptides via palladium enolate formation from beta-ketoamide tags.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: Pemetrexed is used for the chemotherapy of advanced thymoma. Exceptional responses of thymoma to pemetrexed treatment are not frequently observed. The underlying genetic mechanism of the exceptional responses remains unclear. We used whole-exome sequencing to explore the specific genomic aberrations that lead to an extreme and durable response. METHODS: Whole-exome sequencing using NovaSeq6000 (150 bp paired-end sequencing) was performed on nine formalin-fixed paraffin-embedded tissues from patients with advanced thymomas treated with pemetrexed (two exceptional responders and seven typical responders). RESULTS: We identified 284 somatic single-nucleotide variants (SNVs; 272 missense, 8 missense/splice-site, 3 stop-gain, and 1 stop-gain/splice-site), 34 insertions and deletions (Indels; 33 frameshift and one splice region), and 21 copy number variations (CNVs; 15 gains and six losses). No difference in the number of SNVs variants and distribution of deleterious Indels was observed between the exceptional and typical responders. Interestingly, arm-level chromosomal CNVs (15 gains and six losses) were detected in four patients, including an exceptional responder. The highest number of arm-level CNVs was observed in an exceptional responder. CONCLUSION: Exceptional responders to pemetrexed for metastatic thymomas may be characterized by arm-level CNVs. Further, whole-genome and RNA sequencing studies should be performed.", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Tomohiro", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Goto", "name": null }, { "creator_type": "author", "first_name": "Masafumi", "last_name": "Horie", "name": null }, { "creator_type": "author", "first_name": "Ken", "last_name": "Masuda", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Shinno", "name": null }, { "creator_type": "author", "first_name": "Yuji", "last_name": "Matsumoto", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Okuma", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Hidehito", "last_name": "Horinouchi", "name": null }, { "creator_type": "author", "first_name": "Noriko", "last_name": "Motoi", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null }, { "creator_type": "author", "first_name": "Shunichi", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Noboru", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Yuichiro", "last_name": "Ohe", "name": null } ], "identifiers": { "doi": { "normalized": "10.3390/cancers15164018" }, "pmcid": { "normalized": "PMC10452868" }, "pmid": { "normalized": "37627046" } }, "mesh": [], "publication": { "conference_name": null, "date": "2023 Aug 8", "date_precision": "day", "issue": "16", "normalized_date": "2023-08-08", "pages": "", "proceedings_title": null, "publisher": "", "title": "Cancers", "volume": "15", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Whole Exome Sequencing of Thymoma Patients Exhibiting Exceptional Responses to Pemetrexed Monotherapy.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: Ectopic lymphoid structures called tertiary lymphoid tissues (TLTs) develop in several kidney diseases and are associated with poor renal prognosis. However, the mechanisms that expand TLTs and underlie exacerbation of kidney injury remain unclear. METHODS: We performed single-nucleus RNA-sequencing (snRNA-seq) on aged mouse kidneys with TLTs after ischemia-reperfusion injury. The results were validated using immunostaining, in situ hybridization of murine and human kidneys, and in vitro experiments. RESULTS: Using snRNA-seq, we identified proinflammatory and profibrotic Vcam1+ injured proximal tubules (PTs) with NFkappaB and IFN-inducible transcription factor activation. VCAM1+ PTs were preferentially localized around TLTs and drove inflammation and fibrosis via the production of multiple chemokines or cytokines. Lymphocytes within TLTs expressed Tnf and Ifng at high levels, which synergistically upregulated VCAM1 and chemokine expression in cultured PT cells. In addition, snRNA-seq also identified proinflammatory and profibrotic fibroblasts, which resided within and outside TLTs, respectively. Proinflammatory fibroblasts exhibited STAT1 activation and various chemokine or cytokine production, including CXCL9/CXCL10 and B cell activating factor, contributing to lymphocyte recruitment and survival. IFNgamma upregulated the expression of these molecules in cultured fibroblasts in a STAT1-dependent manner, indicating potential bidirectional interactions between IFNgamma-producing CXCR3+ T cells and proinflammatory fibroblasts within TLTs. The cellular and molecular components described in this study were confirmed in human kidneys with TLTs. CONCLUSIONS: These findings suggest that TLTs potentially amplify inflammation by providing a microenvironment that allows intense interactions between renal parenchymal and immune cells. These interactions may serve as novel therapeutic targets in kidney diseases involving TLT formation.", "classifications": [ { "id": "Yamamoto", "label": "Group Yamamoto", "parent": "Toyoshima", "type": "group" }, { "id": "Toyoshima", "label": "Team Toyoshima", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Takahisa", "last_name": "Yoshikawa", "name": null }, { "creator_type": "author", "first_name": "Akiko", "last_name": "Oguchi", "name": null }, { "creator_type": "author", "first_name": "Naoya", "last_name": "Toriu", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Osamu", "last_name": "Ogawa", "name": null }, { "creator_type": "author", "first_name": "Hironori", "last_name": "Haga", "name": null }, { "creator_type": "author", "first_name": "Satoko", "last_name": "Sakurai", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Yasuhiro", "last_name": "Murakawa", "name": null }, { "creator_type": "author", "first_name": "Motoko", "last_name": "Yanagita", "name": null } ], "identifiers": { "doi": { "normalized": "10.1681/asn.0000000000000202" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "37548710" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Chemokine CXCL10", "descriptor_ui": "D054357", "major_topic": false }, { "descriptor": "Chemokine CXCL9", "descriptor_ui": "D054370", "major_topic": false }, { "descriptor": "Chemokines", "descriptor_ui": "D018925", "major_topic": false }, { "descriptor": "Cytokines", "descriptor_ui": "D016207", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Inflammation", "descriptor_ui": "D007249", "major_topic": false }, { "descriptor": "Interferon-gamma", "descriptor_ui": "D007371", "major_topic": false }, { "descriptor": "Kidney", "descriptor_ui": "D007668", "major_topic": false }, { "descriptor": "Lymphoid Tissue", "descriptor_ui": "D008221", "major_topic": true }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Receptors, CXCR3", "descriptor_ui": "D054367", "major_topic": false } ], "publication": { "conference_name": null, "date": "2023 Aug 7", "date_precision": "day", "issue": "", "normalized_date": "2023-08-07", "pages": "", "proceedings_title": null, "publisher": "", "title": "Journal of the American Society of Nephrology : JASN", "volume": "", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Tertiary Lymphoid Tissues Are Microenvironments with Intensive Interactions between Immune Cells and Proinflammatory Parenchymal Cells in Aged Kidneys.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "OBJECTIVES: Immunosuppressive therapy (IST) with antithymocyte globulin (ATG) and cyclosporin A is the standard treatment for aplastic anemia (AA). However, the efficacy of repeated IST with rabbit ATG (rATG) as salvage therapy remains unclear in patients with relapsed or refractory AA. METHODS: We retrospectively evaluated the efficacy and safety of IST2 with rATG (IST2-rATG) in 19 consecutive patients with relapsed or refractory AA who received first-line IST with rATG in two centers between 2009 and 2020. RESULTS: The overall 6-month response rate of the patients was 58%. The response rates were similar between patients with relapsed and refractory AA. The presence of glycophosphatidylinositol-deficient blood cells was associated with a better response to IST2-rATG. Despite retreatment with the same rATG, serum disease and severe allergic reactions were not observed. CONCLUSION: IST2-rATG is effective and safe for the treatment of adult patients with relapsed and refractory AA after receiving first-line IST with rATG.", "classifications": [ { "id": "Nishikii", "label": "Group Nishikii", "parent": "Shintaku", "type": "group" }, { "id": "Shintaku", "label": "Team Shintaku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Tatsuhiro", "last_name": "Sakamoto", "name": null }, { "creator_type": "author", "first_name": "Naoshi", "last_name": "Obara", "name": null }, { "creator_type": "author", "first_name": "Yumiko", "last_name": "Maruyama", "name": null }, { "creator_type": "author", "first_name": "Takayasu", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Naoki", "last_name": "Kurita", "name": null }, { "creator_type": "author", "first_name": "Keiichiro", "last_name": "Hattori", "name": null }, { "creator_type": "author", "first_name": "Yasuhito", "last_name": "Suehara", "name": null }, { "creator_type": "author", "first_name": "Hidekazu", "last_name": "Nishikii", "name": null }, { "creator_type": "author", "first_name": "Yasuhisa", "last_name": "Yokoyama", "name": null }, { "creator_type": "author", "first_name": "Mamiko", "last_name": "Sakata-Yanagimoto", "name": null }, { "creator_type": "author", "first_name": "Kensuke", "last_name": "Usuki", "name": null }, { "creator_type": "author", "first_name": "Shigeru", "last_name": "Chiba", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/ejh.14075" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "37549934" } }, "mesh": [ { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Anemia, Aplastic", "descriptor_ui": "D000741", "major_topic": true }, { "descriptor": "Antilymphocyte Serum", "descriptor_ui": "D000961", "major_topic": true }, { "descriptor": "Cyclosporine", "descriptor_ui": "D016572", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Immunosuppression Therapy", "descriptor_ui": "D007165", "major_topic": false }, { "descriptor": "Immunosuppressive Agents", "descriptor_ui": "D007166", "major_topic": false }, { "descriptor": "Retrospective Studies", "descriptor_ui": "D012189", "major_topic": false }, { "descriptor": "Treatment Outcome", "descriptor_ui": "D016896", "major_topic": false } ], "publication": { "conference_name": null, "date": "2023 Aug 7", "date_precision": "day", "issue": "", "normalized_date": "2023-08-07", "pages": "", "proceedings_title": null, "publisher": "", "title": "European journal of haematology", "volume": "", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Repeated immunosuppressive rabbit antithymocyte globulin therapy for adult patients with relapsed or refractory aplastic anemia.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: This study aimed to elucidate the clinicopathological and molecular features of HER2-amplified and HER2-low colorectal cancers (CRCs). We also characterised HER2 expression statuses in CRCs focusing on their intratumoral heterogeneity and alterations in metastatic lesions to establish practical HER2 status assessment. METHODS: We evaluated 1009 CRCs for HER2 expression and HER2 amplification by immunohistochemistry and FISH, respectively, and correlated the results to clinicopathological and molecular data. For HER2-positive tumours, HER2 expression in metastatic lesions was also assessed. RESULTS: Twenty-five HER2-amplified (2.5%) and 46 HER2-low tumours (4.6%) were identified. HER2-amplified tumours consistently lacked a mucinous component and HER2-low tumours tended to be in the right colon, but no other clinicopathological features were noted. KRAS, NRAS or BRAF mutations were detected in only two HER2-amplified tumours (8%), whereas 23 HER2-low tumours (50%) had one of these mutations. Most HER2-amplified and HER2-low tumours showed a homogeneous or mosaic HER2 expression pattern and a clustered heterogeneous expression pattern was rather rare. HER2 expression was maintained in most metastatic lesions in both HER2-amplified (93%) and HER2-low tumours (81%). CONCLUSIONS: These results suggest that biopsy-based assessment of primary lesions is appropriate for the identification of CRC patients eligible for systemic HER2-targeted therapy.", "classifications": [ { "id": "Hamamoto", "label": "Group Hamamoto", "parent": "Okamoto", "type": "group" }, { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Taiki", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Takayanagi", "name": null }, { "creator_type": "author", "first_name": "Junpei", "last_name": "Yonemaru", "name": null }, { "creator_type": "author", "first_name": "Tomoaki", "last_name": "Naka", "name": null }, { "creator_type": "author", "first_name": "Kengo", "last_name": "Nagashima", "name": null }, { "creator_type": "author", "first_name": "Erika", "last_name": "Machida", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Kohno", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null }, { "creator_type": "author", "first_name": "Yukihide", "last_name": "Kanemitsu", "name": null }, { "creator_type": "author", "first_name": "Ryuji", "last_name": "Hamamoto", "name": null }, { "creator_type": "author", "first_name": "Atsuo", "last_name": "Takashima", "name": null }, { "creator_type": "author", "first_name": "Kouya", "last_name": "Shiraishi", "name": null }, { "creator_type": "author", "first_name": "Shigeki", "last_name": "Sekine", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41416-023-02382-z" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "37543670" } }, "mesh": [ { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Aged, 80 and over", "descriptor_ui": "D000369", "major_topic": false }, { "descriptor": "Colorectal Neoplasms", "descriptor_ui": "D015179", "major_topic": true }, { "descriptor": "Erb-b2 Receptor Tyrosine Kinases", "descriptor_ui": "D018719", "major_topic": true }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Gene Amplification", "descriptor_ui": "D005784", "major_topic": true }, { "descriptor": "Genetic Heterogeneity", "descriptor_ui": "D018740", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Immunohistochemistry", "descriptor_ui": "D007150", "major_topic": false }, { "descriptor": "In Situ Hybridization, Fluorescence", "descriptor_ui": "D017404", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": false }, { "descriptor": "Proto-Oncogene Proteins B-raf", "descriptor_ui": "D048493", "major_topic": false }, { "descriptor": "Proto-Oncogene Proteins p21(ras)", "descriptor_ui": "D016283", "major_topic": false } ], "publication": { "conference_name": null, "date": "2023 Aug 5", "date_precision": "day", "issue": "", "normalized_date": "2023-08-05", "pages": "", "proceedings_title": null, "publisher": "", "title": "British journal of cancer", "volume": "", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "A comprehensive appraisal of HER2 heterogeneity in HER2-amplified and HER2-low colorectal cancer.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "In this study, we propose a mathematical model of self-propelled objects based on the Allen-Cahn type phase-field equation. We combine it with the equation for the concentration of surfactant used in previous studies to construct a model that can handle self-propelled object motion with shape change. A distinctive feature of our mathematical model is that it can represent both deformable self-propelled objects, such as droplets, and solid objects, such as camphor disks, by controlling a single parameter. Furthermore, we demonstrate that, by taking the singular limit, this phase-field based model can be reduced to a free boundary model, which is equivalent to the [Formula: see text]-gradient flow model of self-propelled objects derived by the variational principle from the interfacial energy, which gives a physical interpretation to the phase-field model.", "classifications": [ { "id": "Nagayama", "label": "Group Nagayama", "parent": "Fujiwara", "type": "group" }, { "id": "Fujiwara", "label": "Team Fujiwara", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Masaharu", "last_name": "Nagayama", "name": null }, { "creator_type": "author", "first_name": "Harunori", "last_name": "Monobe", "name": null }, { "creator_type": "author", "first_name": "Koya", "last_name": "Sakakibara", "name": null }, { "creator_type": "author", "first_name": "Ken-Ichi", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Yasuaki", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Kitahata", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41598-023-39395-w" }, "pmcid": { "normalized": "PMC10400585" }, "pmid": { "normalized": "37537247" } }, "mesh": [], "publication": { "conference_name": null, "date": "2023 Aug 3", "date_precision": "day", "issue": "1", "normalized_date": "2023-08-03", "pages": "12633", "proceedings_title": null, "publisher": "", "title": "Scientific reports", "volume": "13", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "On the reaction-diffusion type modelling of the self-propelled object motion.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The adaptive increase in insulin secretion in early stages of obesity serves as a safeguard mechanism to maintain glucose homeostasis that cannot be sustained, and the eventual decompensation of beta cells is a key event in the pathogenesis of diabetes. Here we describe a crucial system orchestrated by a transcriptional cofactor CtBP2. In cultured beta cells, insulin gene expression is coactivated by CtBP2. Global genomic mapping of CtBP2 binding sites identifies a key interaction between CtBP2 and NEUROD1 through which CtBP2 decompacts chromatin in the insulin gene promoter. CtBP2 expression is diminished in pancreatic islets in multiple mouse models of obesity, as well as human obesity. Pancreatic beta cell-specific CtBP2-deficient mice manifest glucose intolerance with impaired insulin secretion. Our transcriptome analysis highlights an essential role of CtBP2 in the maintenance of beta cell integrity. This system provides clues to the molecular basis in obesity and may be targetable to develop therapeutic approaches.", "classifications": [ { "id": "Miyamoto", "label": "Group Miyamoto", "parent": "Wakamoto", "type": "group" }, { "id": "Wakamoto", "label": "Team Wakamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Motohiro", "last_name": "Sekiya", "name": null }, { "creator_type": "author", "first_name": "Yang", "last_name": "Ma", "name": null }, { "creator_type": "author", "first_name": "Kenta", "last_name": "Kainoh", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Daichi", "last_name": "Yamazaki", "name": null }, { "creator_type": "author", "first_name": "Tomomi", "last_name": "Tsuyuzaki", "name": null }, { "creator_type": "author", "first_name": "Wanpei", "last_name": "Chen", "name": null }, { "creator_type": "author", "first_name": "Putu Indah Paramita", "last_name": "Adi Putri", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Ohno", "name": null }, { "creator_type": "author", "first_name": "Takafumi", "last_name": "Miyamoto", "name": null }, { "creator_type": "author", "first_name": "Yoshinori", "last_name": "Takeuchi", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Murayama", "name": null }, { "creator_type": "author", "first_name": "Yoko", "last_name": "Sugano", "name": null }, { "creator_type": "author", "first_name": "Yoshinori", "last_name": "Osaki", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Iwasaki", "name": null }, { "creator_type": "author", "first_name": "Naoya", "last_name": "Yahagi", "name": null }, { "creator_type": "author", "first_name": "Hiroaki", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Kaori", "last_name": "Motomura", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Matsuzaka", "name": null }, { "creator_type": "author", "first_name": "Kazuya", "last_name": "Murata", "name": null }, { "creator_type": "author", "first_name": "Seiya", "last_name": "Mizuno", "name": null }, { "creator_type": "author", "first_name": "Satoru", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Shimano", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.celrep.2023.112914" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "37557182" } }, "mesh": [ { "descriptor": "Alcohol Oxidoreductases", "descriptor_ui": "D000429", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Co-Repressor Proteins", "descriptor_ui": "D056970", "major_topic": false }, { "descriptor": "Glucose", "descriptor_ui": "D005947", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Insulin", "descriptor_ui": "D007328", "major_topic": false }, { "descriptor": "Insulin Secretion", "descriptor_ui": "D000078790", "major_topic": false }, { "descriptor": "Insulin-Secreting Cells", "descriptor_ui": "D050417", "major_topic": true }, { "descriptor": "Islets of Langerhans", "descriptor_ui": "D007515", "major_topic": true }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Obesity", "descriptor_ui": "D009765", "major_topic": true } ], "publication": { "conference_name": null, "date": "2023 Aug 1", "date_precision": "day", "issue": "", "normalized_date": "2023-08-01", "pages": "112914", "proceedings_title": null, "publisher": "", "title": "Cell reports", "volume": "", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Loss of CtBP2 may be a mechanistic link between metabolic derangements and progressive impairment of pancreatic beta cell function.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The ErbB-family receptors play pivotal roles in the proliferation, migration, and survival of epithelial cells. Because our knowledge on the ErbB-family receptors was obtained largely by the exogenous application of their ligands, it remains unknown to which extent each of the ErbB contributes to these outputs. We here knocked out each ErbB gene, various combinations of ErbB genes, or all in Madin-Darby canine kidney cells to delineate the contribution of each gene. ERK activation waves during collective cell migration were mediated primarily by ErbB1 and secondarily by the ErbB2/ErbB3 heterodimer. Either ErbB1 or the ErbB2/ErbB3 complex was sufficient for the G1/S progression. The saturation cell density was markedly reduced in cells deficient in all ErbB-proteins, but not cells retaining only ErbB2, which cannot bind to ligands. Thus, the ligand-independent ErbB2 activity is sufficient for preventing apoptosis at high cell density. In short, systematic knockout of ErbB-family genes delineated the roles of each ErbB receptor.", "classifications": [ { "id": "Sawano", "label": "Group Sawano", "parent": "Shintaku", "type": "group" }, { "id": "Shintaku", "label": "Team Shintaku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Kimiya", "last_name": "Matsuda", "name": null }, { "creator_type": "author", "first_name": "Daiki", "last_name": "Hirayama", "name": null }, { "creator_type": "author", "first_name": "Naoya", "last_name": "Hino", "name": null }, { "creator_type": "author", "first_name": "Sota", "last_name": "Kuno", "name": null }, { "creator_type": "author", "first_name": "Asako", "last_name": "Sakaue-Sawano", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Miyawaki", "name": null }, { "creator_type": "author", "first_name": "Michiyuki", "last_name": "Matsuda", "name": null }, { "creator_type": "author", "first_name": "Kenta", "last_name": "Terai", "name": null } ], "identifiers": { "doi": { "normalized": "10.1242/jcs.261199" }, "pmcid": { "normalized": null }, "pmid": { "normalized": null } }, "mesh": [], "publication": { "conference_name": null, "date": "2023-07-31", "date_precision": "day", "issue": "", "normalized_date": "2023-07-31", "pages": "jcs.261199", "proceedings_title": null, "publisher": "", "title": "Journal of Cell Science", "volume": "", "year": 2023 }, "ssbd": { "database": [], "repository": [ "ssbd-repos-000265" ] }, "title": "Knockout of all ErbB-family genes delineates their roles in proliferation, survival, and migration", "url": "https://doi.org/10.1242/jcs.261199", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The demand for practical methods for the synthesis of novel fluoroalkyl molecules is increasing owing to their diverse applications. Our group has achieved efficient difunctionalizing fluoroalkylations of alkenes using fluorinated carboxylic anhydrides as user-friendly fluoroalkyl sources. Fluorinated diacyl peroxide, prepared in situ from carboxylic anhydrides, enables the development of novel reactions when used as a radical fluoroalkylating reagent. In this account, we aim to provide an in-depth understanding of the structure, bonding, and reactivity of fluorinated diacyl peroxides and radicals as well as their control in fluoroalkylation reactions. In the first part of this account, the physical properties and reactivity of diacyl peroxides and fluoroalkyl radicals are described. In the subsequent part, we categorize the reactions into copper-catalyzed and metal-free methods utilizing the oxidizing properties of fluorinated diacyl peroxides. We also outline examples and mechanisms.", "classifications": [ { "id": "Sodeoka", "label": "Group Sodeoka", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Shintaro", "last_name": "Kawamura", "name": null }, { "creator_type": "author", "first_name": "Mikiko", "last_name": "Sodeoka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/tcr.202300202" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "37522613" } }, "mesh": [], "publication": { "conference_name": null, "date": "2023 Jul 31", "date_precision": "day", "issue": "", "normalized_date": "2023-07-31", "pages": "e202300202", "proceedings_title": null, "publisher": "", "title": "Chemical record (New York, N.Y.)", "volume": "", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Understanding and Controlling Fluorinated Diacyl Peroxides and Fluoroalkyl Radicals in Alkene Fluoroalkylations.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The excessive inflammatory response of macrophages plays a vital role in the pathogenesis of various diseases. The dynamic metabolic alterations in macrophages, including amino acid metabolism, are known to orchestrate their inflammatory phenotype. To explore a new metabolic pathway that regulates the inflammatory response, we examined metabolome changes in mouse peritoneal macrophages (PMs) in response to lipopolysaccharide (LPS) and found a coordinated increase of cysteine and its related metabolites, suggesting an enhanced demand for cysteine during the inflammatory response. Because Slc7a11, which encodes a cystine transporter xCT, was remarkably upregulated upon the pro-inflammatory challenge and found to serve as a major channel of cysteine supply, we examined the inflammatory behavior of Slc7a11 knockout PMs (xCT-KO PMs) to clarify an impact of the increased cysteine demand on inflammation. The xCT-KO PMs exhibited a prolonged upregulation of pro-inflammatory genes, which was recapitulated by cystine depletion in the culture media of wild-type PMs, suggesting that cysteine facilitates the resolution of inflammation. Detailed analysis of the sulfur metabolome revealed that supersulfides, such as cysteine persulfide, were increased in PMs in response to LPS, which was abolished in xCT-KO PMs. Supplementation of N-acetylcysteine tetrasulfide (NAC-S2), a supersulfide donor, attenuated the pro-inflammatory gene expression in xCT-KO PMs. Thus, activated macrophages increase cystine uptake via xCT and produce supersulfides, creating a negative feedback loop to limit excessive inflammation. Our study highlights the finely tuned regulation of macrophage inflammatory response by sulfur metabolism.", "classifications": [ { "id": "Akaike", "label": "Group Akaike", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Haruna", "last_name": "Takeda", "name": null }, { "creator_type": "author", "first_name": "Shohei", "last_name": "Murakami", "name": null }, { "creator_type": "author", "first_name": "Zun", "last_name": "Liu", "name": null }, { "creator_type": "author", "first_name": "Tomohiro", "last_name": "Sawa", "name": null }, { "creator_type": "author", "first_name": "Masatomo", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Yoshihiro", "last_name": "Izumi", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Bamba", "name": null }, { "creator_type": "author", "first_name": "Hideyo", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Takaaki", "last_name": "Akaike", "name": null }, { "creator_type": "author", "first_name": "Hiroki", "last_name": "Sekine", "name": null }, { "creator_type": "author", "first_name": "Hozumi", "last_name": "Motohashi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.redox.2023.102834" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "37536084" } }, "mesh": [ { "descriptor": "Acetylcysteine", "descriptor_ui": "D000111", "major_topic": false }, { "descriptor": "Amino Acid Transport System y+", "descriptor_ui": "D027182", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cystine", "descriptor_ui": "D003553", "major_topic": true }, { "descriptor": "Feedback", "descriptor_ui": "D005246", "major_topic": false }, { "descriptor": "Lipopolysaccharides", "descriptor_ui": "D008070", "major_topic": true }, { "descriptor": "Macrophages", "descriptor_ui": "D008264", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Sulfur", "descriptor_ui": "D013455", "major_topic": false } ], "publication": { "conference_name": null, "date": "2023 Jul 29", "date_precision": "day", "issue": "", "normalized_date": "2023-07-29", "pages": "102834", "proceedings_title": null, "publisher": "", "title": "Redox biology", "volume": "65", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Sulfur metabolic response in macrophage limits excessive inflammatory response by creating a negative feedback loop.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Association fibers connect different areas of the cerebral cortex over long distances and integrate information to achieve higher brain functions, particularly in humans. Prototyped association fibers are developed to the respective tangential direction throughout the cerebral hemispheres along the deepest border of the subplate during the fetal period. However, how guidance to remote areas is achieved is not known. Because the subplate is located below the cortical surface, the tangential direction of the fibers may be biased by the curved surface geometry due to Sylvian fissure and cortical poles. The fiber length can be minimized if the tracts follow the shortest paths (geodesics) of the curved surface. Here, we propose and examine a theory that geodesics guide the tangential direction of long association fibers by analyzing how geodesics are spatially distributed on the fetal human brains. We found that the geodesics were dense on the saddle-shaped surface of the perisylvian region and sparse on the dome-shaped cortical poles. The geodesics corresponded with the arrangement of five typical association fibers, supporting the theory. Thus, the geodesic theory provides directional guidance information for wiring remote areas and suggests that long association fibers emerge from minimizing their tangential length in fetal brains.", "classifications": [ { "id": "JPMJCR2121", "label": "JPMJCR2121", "researcher": "Minako Ueda", "type": "grant" }, { "id": "Fujimoto", "label": "Group Fujimoto", "parent": "Ueda", "type": "group" }, { "id": "Ueda", "label": "Group Ueda", "parent": "Ueda", "type": "group" }, { "id": "Ueda", "label": "Team Ueda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Kazuya", "last_name": "Horibe", "name": null }, { "creator_type": "author", "first_name": "Gentaro", "last_name": "Taga", "name": null }, { "creator_type": "author", "first_name": "Koichi", "last_name": "Fujimoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1093/cercor/bhad243" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "37482884" } }, "mesh": [ { "descriptor": "Cerebral Cortex", "descriptor_ui": "D002540", "major_topic": true }, { "descriptor": "Fetus", "descriptor_ui": "D005333", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false } ], "publication": { "conference_name": null, "date": "2023 Jul 24", "date_precision": "day", "issue": "", "normalized_date": "2023-07-24", "pages": "bhad243", "proceedings_title": null, "publisher": "", "title": "Cerebral cortex (New York, N.Y. : 1991)", "volume": "", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Geodesic theory of long association fibers arrangement in the human fetal cortex.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Tumors contain various stromal cells, such as immune cells, endothelial cells, and fibroblasts, which contribute to the development of a tumor-specific microenvironment characterized by hypoxia and inflammation, and are associated with malignant progression. In this study, we investigated the activity of intratumoral hypoxia-inducible factor (HIF), which functions as a master regulator of the cellular response to hypoxia and inflammation. We constructed the HIF activity-monitoring reporter gene hypoxia-response element-Venus-Akaluc (HVA) that expresses the green fluorescent protein Venus and modified firefly luciferase Akaluc in a HIF activity-dependent manner, and created transgenic mice harboring HVA transgene (HVA-Tg). In HVA-Tg, HIF-active cells can be visualized using AkaBLI, an ultra-sensitive in vivo bioluminescence imaging technology that produces an intense near-infrared light upon reaction of Akaluc with the D-luciferin analog AkaLumine-HCl. By orthotopic transplantation of E0771, a mouse triple negative breast cancer cell line without a reporter gene, into HVA-Tg, we succeeded in noninvasively monitoring bioluminescence signals from HIF-active stromal cells as early as 8 days after transplantation. The HIF-active stromal cells initially clustered locally and then spread throughout the tumors with growth. Immunohistochemistry and flow cytometry analyses revealed that CD11b+F4/80+ macrophages were the predominant HIF-active stromal cells in E0771 tumors. These results indicate that HVA-Tg is a useful tool for spatiotemporal analysis of HIF-active tumor stromal cells, facilitating investigation of the roles of HIF-active tumor stromal cells in tumor growth and malignant progression.", "classifications": [ { "id": "Kuchimaru", "label": "Group Kuchimaru", "parent": "Shintaku", "type": "group" }, { "id": "Shintaku", "label": "Team Shintaku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Hitomi", "last_name": "Miyabara", "name": null }, { "creator_type": "author", "first_name": "Ryuichiro", "last_name": "Hirano", "name": null }, { "creator_type": "author", "first_name": "Shigeaki", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "John Clyde Co", "last_name": "Soriano", "name": null }, { "creator_type": "author", "first_name": "Hitomi", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Takahiro", "last_name": "Kuchimaru", "name": null }, { "creator_type": "author", "first_name": "Nobuo", "last_name": "Kitada", "name": null }, { "creator_type": "author", "first_name": "Tetsuya", "last_name": "Kadonosono", "name": null }, { "creator_type": "author", "first_name": "Shojiro A.", "last_name": "Maki", "name": null }, { "creator_type": "author", "first_name": "Gen", "last_name": "Kondoh", "name": null }, { "creator_type": "author", "first_name": "Shinae", "last_name": "Kizaka-Kondoh", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/cas.15907" }, "pmcid": { "normalized": null }, "pmid": { "normalized": null } }, "mesh": [], "publication": { "conference_name": null, "date": "2023 Jul 22", "date_precision": "day", "issue": "n/a", "normalized_date": "2023-07-22", "pages": "", "proceedings_title": null, "publisher": "", "title": "Cancer Science", "volume": "n/a", "year": 2023 }, "ssbd": { "database": [ "ssbd-database-000332" ], "repository": [ "ssbd-repos-000332" ] }, "title": "In vivo optical imaging of tumor stromal cells with hypoxia-inducible factor activity", "url": "https://onlinelibrary.wiley.com/doi/abs/10.1111/cas.15907", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Neurons decline in their functionality over time, and age-related neuronal alterations are associated with phenotypes of neurodegenerative diseases. In nonneural tissues, an infolded nuclear shape has been proposed as a hallmark of aged cells and neurons with infolded nuclei have also been reported to be associated with neuronal activity. Here, we performed time-lapse imaging in the visual cortex of Nex-Cre;SUN1-GFP mice. Nuclear infolding was observed within 10 min of stimulation in young nuclei, while the aged nuclei were already infolded pre-stimulation and showed reduced dynamics of the morphology. In young nuclei, the depletion of the stimuli restored the nucleus to a spherical shape and reduced the dynamic behavior, suggesting that nuclear infolding is a reversible process. We also found the aged nucleus to be stiffer than the young one, further relating to the age-associated loss of nuclear shape dynamics. We reveal temporal changes in the nuclear shape upon external stimulation and observe that these morphological dynamics decrease with age.", "classifications": [ { "id": "Maki", "label": "Group Maki", "parent": "Toyoshima", "type": "group" }, { "id": "Toyoshima", "label": "Team Toyoshima", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Tanita", "last_name": "Frey", "name": null }, { "creator_type": "author", "first_name": "Tomonari", "last_name": "Murakami", "name": null }, { "creator_type": "author", "first_name": "Koichiro", "last_name": "Maki", "name": null }, { "creator_type": "author", "first_name": "Takumi", "last_name": "Kawaue", "name": null }, { "creator_type": "author", "first_name": "Naoki", "last_name": "Tani", "name": null }, { "creator_type": "author", "first_name": "Ayaka", "last_name": "Sugai", "name": null }, { "creator_type": "author", "first_name": "Naotaka", "last_name": "Nakazawa", "name": null }, { "creator_type": "author", "first_name": "Kei-ichiro", "last_name": "Ishiguro", "name": null }, { "creator_type": "author", "first_name": "Taiji", "last_name": "Adachi", "name": null }, { "creator_type": "author", "first_name": "Mineko", "last_name": "Kengaku", "name": null }, { "creator_type": "author", "first_name": "Kenichi", "last_name": "Ohki", "name": null }, { "creator_type": "author", "first_name": "Yukiko", "last_name": "Gotoh", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Kishi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/acel.13925" }, "pmcid": { "normalized": null }, "pmid": { "normalized": null } }, "mesh": [], "publication": { "conference_name": null, "date": "2023 Jul 21", "date_precision": "day", "issue": "n/a", "normalized_date": "2023-07-21", "pages": "e13925", "proceedings_title": null, "publisher": "", "title": "Aging Cell", "volume": "n/a", "year": 2023 }, "ssbd": { "database": [], "repository": [ "ssbd-repos-000302" ] }, "title": "Age-associated reduction of nuclear shape dynamics in excitatory neurons of the visual cortex", "url": "https://onlinelibrary.wiley.com/doi/abs/10.1111/acel.13925", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Cell proliferation is a fundamental process underlying embryogenesis, homeostasis, wound healing, and cancer. The process involves multiple events during each cell cycle, such as cell growth, contractile ring formation, and division to daughter cells, which affect the surrounding cell population geometrically and mechanically. However, existing methods do not comprehensively describe the dynamics of multicellular structures involving cell proliferation at a subcellular resolution. In this study, we present a novel model for proliferative multicellular dynamics at the subcellular level by building upon the nonconservative fluid membrane (NCF) model that we developed in earlier research. The NCF model utilizes a dynamically-rearranging closed triangular mesh to depict the shape of each cell, enabling us to analyze cell dynamics over extended periods beyond each cell cycle, during which cell surface components undergo dynamic turnover. The proposed model represents the process of cell proliferation by incorporating cell volume growth and contractile ring formation through an energy function and topologically dividing each cell at the cleavage furrow formed by the ring. Numerical simulations demonstrated that the model recapitulated the process of cell proliferation at subcellular resolution, including cell volume growth, cleavage furrow formation, and division to daughter cells. Further analyses suggested that the orientation of actomyosin stress in the contractile ring plays a crucial role in the cleavage furrow formation, i.e., circumferential orientation can form a cleavage furrow but isotropic orientation cannot. Furthermore, the model replicated tissue-scale multicellular dynamics, where the successive proliferation of adhesive cells led to the formation of a cell sheet and stratification on the substrate. Overall, the proposed model provides a basis for analyzing proliferative multicellular dynamics at subcellular resolution.", "classifications": [ { "id": "JPMJCR1921", "label": "JPMJCR1921", "researcher": "Itaru Imayoshi", "type": "grant" }, { "id": "Imayoshi", "label": "Group Imayoshi", "parent": "Imayoshi", "type": "group" }, { "id": "Imayoshi", "label": "Team Imayoshi", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Satoru", "last_name": "Okuda", "name": null }, { "creator_type": "author", "first_name": "Tetsuya", "last_name": "Hiraiwa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1140/epje/s10189-023-00315-5" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "37466721" } }, "mesh": [ { "descriptor": "Actin Cytoskeleton", "descriptor_ui": "D008841", "major_topic": true }, { "descriptor": "Cell Division", "descriptor_ui": "D002455", "major_topic": false }, { "descriptor": "Cell Membrane", "descriptor_ui": "D002462", "major_topic": false } ], "publication": { "conference_name": null, "date": "2023 Jul 19", "date_precision": "day", "issue": "7", "normalized_date": "2023-07-19", "pages": "56", "proceedings_title": null, "publisher": "", "title": "The European physical journal. E, Soft matter", "volume": "46", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Modelling contractile ring formation and division to daughter cells for simulating proliferative multicellular dynamics.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Hyalinizing clear cell carcinoma (HCCC) is a rare indolent malignant tumor of minor salivary gland origin with EWSR1::ATF1 rearrangement. Pathologically, the tumor cells possess a clear cytoplasm in a background of hyalinized stroma. Generally, the tumor cells are positive for p63 and p40, and negative for s100 and alphaSMA, suggesting that they differentiate into squamous epithelium and not into myoepithelium. In this study, we performed a detailed histopathological and genomic analysis of six cases of HCCC including two atypical subtypes-a case of \"high-grade transformation\" and one with \"possessing a novel partner gene for EWSR1.\" We performed a sequential analysis of the primary and recurrent tumor by whole-exome sequencing, RNA sequencing, Sanger sequencing, and fluorescence in situ hybridization (FISH) to investigate the effect of genomic changes on histopathology and clinical prognosis. A fusion gene involving the EWSR1 gene was detected in all cases. Five cases, including the \"high-grade transformation,\" harbored a known EWSR1::ATF1 fusion gene; however, one case harbored a novel EWSR1::LARP4 fusion gene. This novel EWSR1::LARP4 fused HCCC has a SOX10 positive staining which is different from the EWSR1::ATF1 fused HCCC. According to whole-exome sequencing and FISH analysis, the \"Whole-genome doubling\" and, focal deletion involving CDKN2A, CDKN2B and PTEN were detected in HCCC with \"high-grade transformation\". Conclusively, we identified a novel partner gene for EWSR1, LARP4, in indolent HCCC. Importantly, \"high-grade transformation\" and poor prognosis were caused by whole genome doubling and subsequent genomic aberrations.", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Kenya", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Masahito", "last_name": "Kawazu", "name": null }, { "creator_type": "author", "first_name": "Seiichi", "last_name": "Yoshimoto", "name": null }, { "creator_type": "author", "first_name": "Toshihide", "last_name": "Ueno", "name": null }, { "creator_type": "author", "first_name": "Go", "last_name": "Omura", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Mizuo", "last_name": "Ando", "name": null }, { "creator_type": "author", "first_name": "Eigitsu", "last_name": "Ryo", "name": null }, { "creator_type": "author", "first_name": "Airi", "last_name": "Sakyo", "name": null }, { "creator_type": "author", "first_name": "Akihiko", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Mano", "name": null }, { "creator_type": "author", "first_name": "Taisuke", "last_name": "Mori", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.labinv.2023.100213" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "37479138" } }, "mesh": [ { "descriptor": "Adenocarcinoma, Clear Cell", "descriptor_ui": "D018262", "major_topic": true }, { "descriptor": "Base Sequence", "descriptor_ui": "D001483", "major_topic": false }, { "descriptor": "Carcinoma", "descriptor_ui": "D002277", "major_topic": true }, { "descriptor": "Genes, cdc", "descriptor_ui": "D018816", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "In Situ Hybridization, Fluorescence", "descriptor_ui": "D017404", "major_topic": false }, { "descriptor": "Oncogene Proteins, Fusion", "descriptor_ui": "D015514", "major_topic": false }, { "descriptor": "RNA-Binding Protein EWS", "descriptor_ui": "D034802", "major_topic": false }, { "descriptor": "Salivary Gland Neoplasms", "descriptor_ui": "D012468", "major_topic": true }, { "descriptor": "Salivary Glands", "descriptor_ui": "D012469", "major_topic": false }, { "descriptor": "SOXE Transcription Factors", "descriptor_ui": "D055757", "major_topic": false } ], "publication": { "conference_name": null, "date": "2023 Jul 19", "date_precision": "day", "issue": "", "normalized_date": "2023-07-19", "pages": "100213", "proceedings_title": null, "publisher": "", "title": "Laboratory investigation; a journal of technical methods and pathology", "volume": "", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Genome doubling shapes high-grade transformation and novel EWSR1::LARP4 fusion shows SOX10 immunostaining in hyalinizing clear cell carcinoma of salivary gland.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "We aimed to investigate the impact of glutathione trisulfide (GSSSG) on lipopolysaccharide (LPS)-induced inflammation in retinal glia. Inflammatory responses in mouse-derived glial cells and Wistar rat retinas were stimulated with administration of LPS. Cell survival and proinflammatory cytokine production were examined using the Calcein-AM assay, and reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and enzyme-linked immunosorbent assay (ELISA), respectively. Retinal microglia were visualized with immunohistochemistry for Iba1. Administration of LPS (10 microg/mL) or GSSSG (less than 100 microM) did not affect survival of cultured primary Muller cells and established microglial cells (BV-2). RT-qPCR and ELISA indicated that GSSSG inhibited LPS-induced gene upregulation and protein secretion of proinflammatory cytokines in these glial cells and rat retinas. GSSSG inhibited LPS-induced activation of TGF-beta-activated kinase 1 (TAK1), which is an upstream kinase of NF-kappaB, in BV-2 cells. Finally, in vivo experiments indicated that intravitreal administration of GSSSG but not its relative glutathione disulfide (GSSG) inhibited LPS (500 ng)-induced accumulation of Iba1-immunopositive microglia in rat retinas. Taken together, GSSSG has the potential to prevent pathogenesis of inflammation-associated ocular diseases by inhibiting proinflammatory cytokine expression in retinal glial cells.", "classifications": [ { "id": "Akaike", "label": "Group Akaike", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Tawarayama", "name": null }, { "creator_type": "author", "first_name": "Kota", "last_name": "Umeki", "name": null }, { "creator_type": "author", "first_name": "Maki", "last_name": "Inoue-Yanagimachi", "name": null }, { "creator_type": "author", "first_name": "Naoki", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Hirokazu", "last_name": "Hasegawa", "name": null }, { "creator_type": "author", "first_name": "Noriko", "last_name": "Himori", "name": null }, { "creator_type": "author", "first_name": "Satoru", "last_name": "Tsuda", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Kunikata", "name": null }, { "creator_type": "author", "first_name": "Takaaki", "last_name": "Akaike", "name": null }, { "creator_type": "author", "first_name": "Toru", "last_name": "Nakazawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41598-023-38696-4" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "37460786" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cytokines", "descriptor_ui": "D016207", "major_topic": false }, { "descriptor": "Glutathione", "descriptor_ui": "D005978", "major_topic": false }, { "descriptor": "Inflammation", "descriptor_ui": "D007249", "major_topic": true }, { "descriptor": "Lipopolysaccharides", "descriptor_ui": "D008070", "major_topic": true }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Microglia", "descriptor_ui": "D017628", "major_topic": false }, { "descriptor": "Neuroglia", "descriptor_ui": "D009457", "major_topic": false }, { "descriptor": "NF-kappa B", "descriptor_ui": "D016328", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Rats, Wistar", "descriptor_ui": "D017208", "major_topic": false } ], "publication": { "conference_name": null, "date": "2023 Jul 17", "date_precision": "day", "issue": "1", "normalized_date": "2023-07-17", "pages": "11513", "proceedings_title": null, "publisher": "", "title": "Scientific reports", "volume": "13", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Glutathione trisulfide prevents lipopolysaccharide-induced retinal inflammation via inhibition of proinflammatory cytokine production in glial cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "N,N-Dimethylformamide (DMF) is an essential solvent in industries and pharmaceutics. Its market size range was estimated to be 2 billion U.S. dollars in 2022. Monitoring DMF in solution environments in real time is significant because of its toxicity. However, DMF is not a redox-active molecule; therefore, selective monitoring of DMF in solutions, especially in polar aqueous solutions, in real time is extremely difficult. In this paper, we propose a selective DMF sensor using a molybdenum disulfide (MoS(2)) field-effect transistor (FET). The sensor responds to DMF molecules but not to similar molecules of formamide, N,N-diethylformamide, and N,N-dimethylacetamide. The plausible atomic mechanism is the oxygen substitution sites on MoS(2), on which the DMF molecule shows an exceptional orientation. The thin structure of MoS(2)-FET can be incorporated into a microfluidic chamber, which leads to DMF monitoring in real time by exchanging solutions subsequently. The designed device shows DMF monitoring in NaCl ionic solutions from 1 to 200 muL/mL. This work proposes the concept of selectively monitoring redox-inactive molecules based on the nonideal atomic affinity site on the surface of two-dimensional semiconductors.", "classifications": [ { "id": "Hijikata", "label": "Group Hijikata", "parent": "Tsuchiya", "type": "group" }, { "id": "Tsuchiya", "label": "Team Tsuchiya", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Akito", "last_name": "Fukui", "name": null }, { "creator_type": "author", "first_name": "Keigo", "last_name": "Matsuyama", "name": null }, { "creator_type": "author", "first_name": "Hiroaki", "last_name": "Onoe", "name": null }, { "creator_type": "author", "first_name": "Shun", "last_name": "Itai", "name": null }, { "creator_type": "author", "first_name": "Hidekazu", "last_name": "Ikeno", "name": null }, { "creator_type": "author", "first_name": "Shunsuke", "last_name": "Hiraoka", "name": null }, { "creator_type": "author", "first_name": "Kousei", "last_name": "Hiura", "name": null }, { "creator_type": "author", "first_name": "Yuh", "last_name": "Hijikata", "name": null }, { "creator_type": "author", "first_name": "Jenny", "last_name": "Pirillo", "name": null }, { "creator_type": "author", "first_name": "Takahiro", "last_name": "Nagata", "name": null }, { "creator_type": "author", "first_name": "Kuniharu", "last_name": "Takei", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Yoshimura", "name": null }, { "creator_type": "author", "first_name": "Norifumi", "last_name": "Fujimura", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Kiriya", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/acsnano.3c03915" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "37458690" } }, "mesh": [], "publication": { "conference_name": null, "date": "2023 Jul 17", "date_precision": "day", "issue": "", "normalized_date": "2023-07-17", "pages": "", "proceedings_title": null, "publisher": "", "title": "ACS nano", "volume": "", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Unusual Selective Monitoring of N,N-Dimethylformamide in a Two-Dimensional Material Field-Effect Transistor.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND AND OBJECTIVES: This study examined the trend of hazards for postoperative recurrence of lung cancer according to pathologic stages. METHODS: We reviewed the records of 1987 patients who underwent resection for lung cancer between 2007 and 2012. Postoperative recurrence and development of second primary lung cancer were analyzed to evaluate the trend of hazard rate. RESULTS: Recurrence-free survival (RFS) probabilities at 5 postoperative years in patients with stage I/II/III disease were 87.8%/54.7%,/33.4%, respectively. The hazard rate of RFS was consistently low (<0.005) for stage I patients for 5 years after surgery. The hazard rate of RFS for stage II patients showed a peak of 0.016 at 12.4 months after surgery, and that for stage III patients had a higher peak of 0.029 at 13.7 months after surgery, after which they showed a gradual decrease. The hazard rate for the development of second primary lung cancer exceeded that of recurrence of first primary lung cancer after 72 months postoperatively. CONCLUSIONS: Short-interval postoperative surveillance might be unnecessary for stage I patients but should be considered in stage II/III patients. Screening of second primary lung cancer rather than surveillance of recurrence might be beneficial after more than 6 years postoperatively.", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yuji", "last_name": "Muraoka", "name": null }, { "creator_type": "author", "first_name": "Masaya", "last_name": "Yotsukura", "name": null }, { "creator_type": "author", "first_name": "Yukihiro", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Kazuo", "last_name": "Nakagawa", "name": null }, { "creator_type": "author", "first_name": "Kouya", "last_name": "Shiraishi", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Kohno", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null }, { "creator_type": "author", "first_name": "Shun-Ichi", "last_name": "Watanabe", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/jso.27395" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "37458135" } }, "mesh": [ { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Aged, 80 and over", "descriptor_ui": "D000369", "major_topic": false }, { "descriptor": "Carcinoma, Non-Small-Cell Lung", "descriptor_ui": "D002289", "major_topic": true }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Follow-Up Studies", "descriptor_ui": "D005500", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Lung Neoplasms", "descriptor_ui": "D008175", "major_topic": true }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Neoplasm Recurrence, Local", "descriptor_ui": "D009364", "major_topic": true }, { "descriptor": "Neoplasm Staging", "descriptor_ui": "D009367", "major_topic": false }, { "descriptor": "Neoplasms, Second Primary", "descriptor_ui": "D016609", "major_topic": true }, { "descriptor": "Pneumonectomy", "descriptor_ui": "D011013", "major_topic": false }, { "descriptor": "Retrospective Studies", "descriptor_ui": "D012189", "major_topic": false }, { "descriptor": "Survival Rate", "descriptor_ui": "D015996", "major_topic": false } ], "publication": { "conference_name": null, "date": "2023 Jul 17", "date_precision": "day", "issue": "", "normalized_date": "2023-07-17", "pages": "", "proceedings_title": null, "publisher": "", "title": "Journal of surgical oncology", "volume": "", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Dynamics of recurrence after curative resection of nonsmall cell lung cancer.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Gravitropism is the plant organ bending in response to gravity, while a straightening mechanism prevents bending beyond the gravitropic set-point angle. The promotion and prevention of bending occur simultaneously around the inflorescence stem tip. How these two opposing forces work together and what part of the stem they affect are unknown. To understand the mechanical forces involved, we rotated wild type and organ-straightening-deficient mutant (myosin xif xik) Arabidopsis plants to a horizontal position to initiate bending. The mutant stems started to bend before the wild-type stems, which led us to hypothesize that the force preventing bending was weaker in mutant. We modeled the wild-type and mutant stems as elastic rods, and evaluated two parameters: an organ-angle-dependent gravitropic-responsive parameter (beta) and an organ-curvature-dependent proprioceptive-responsive parameter (gamma). Our model showed that these two parameters were lower in mutant than in wild type, implying that, unexpectedly, both promotion and prevention of bending are weak in mutant. Subsequently, finite element method simulations revealed that the compressive stress in the middle of the stem was significantly lower in wild type than in mutant. The results of this study show that myosin-XIk-and-XIf-dependent organ straightening adjusts the stress distribution to achieve a mechanically favorable shape.", "classifications": [ { "id": "JPMJCR2121", "label": "JPMJCR2121", "researcher": "Minako Ueda", "type": "grant" }, { "id": "Tsugawa", "label": "Group Tsugawa", "parent": "Ueda", "type": "group" }, { "id": "Ueda", "label": "Group Ueda", "parent": "Ueda", "type": "group" }, { "id": "Ueda", "label": "Team Ueda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Satoru", "last_name": "Tsugawa", "name": null }, { "creator_type": "author", "first_name": "Yuzuki", "last_name": "Miyake", "name": null }, { "creator_type": "author", "first_name": "Keishi", "last_name": "Okamoto", "name": null }, { "creator_type": "author", "first_name": "Masatsugu", "last_name": "Toyota", "name": null }, { "creator_type": "author", "first_name": "Hiroki", "last_name": "Yagi", "name": null }, { "creator_type": "author", "first_name": "Miyo", "last_name": "Terao Morita", "name": null }, { "creator_type": "author", "first_name": "Ikuko", "last_name": "Hara-Nishimura", "name": null }, { "creator_type": "author", "first_name": "Taku", "last_name": "Demura", "name": null }, { "creator_type": "author", "first_name": "Haruko", "last_name": "Ueda", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41598-023-38069-x" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "37460700" } }, "mesh": [ { "descriptor": "Arabidopsis", "descriptor_ui": "D017360", "major_topic": true }, { "descriptor": "Arabidopsis Proteins", "descriptor_ui": "D029681", "major_topic": true }, { "descriptor": "Gravitation", "descriptor_ui": "D006112", "major_topic": false }, { "descriptor": "Gravitropism", "descriptor_ui": "D018522", "major_topic": false }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": false }, { "descriptor": "Myosins", "descriptor_ui": "D009218", "major_topic": false } ], "publication": { "conference_name": null, "date": "2023 Jul 17", "date_precision": "day", "issue": "1", "normalized_date": "2023-07-17", "pages": "11165", "proceedings_title": null, "publisher": "", "title": "Scientific reports", "volume": "13", "year": 2023 }, "ssbd": { "database": [ "ssbd-database-000333" ], "repository": [ "ssbd-repos-000333" ] }, "title": "Shoot gravitropism and organ straightening cooperate to arrive at a mechanically favorable shape in Arabidopsis.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The enteric nervous system (ENS) regulates gut functions independently from the central nervous system (CNS) by its highly autonomic neural circuit that integrates diverse neuronal subtypes. Although several transcription factors are shown to be necessary for the generation of some enteric neuron subtypes, the mechanisms underlying neuronal subtype specification in the ENS remain elusive. In this study, we examined the biological function of Polycomb group RING finger protein 1 (PCGF1), one of the epigenetic modifiers, in the development and differentiation of the ENS by disrupting the Pcgf1 gene selectively in the autonomic-lineage cells. Although ENS precursor migration and enteric neurogenesis were largely unaffected, neuronal differentiation was impaired in the Pcgf1-deficient mice, with the numbers of neurons expressing somatostatin (Sst(+) ) decreased in multiple gut regions. Notably, the decrease in Sst(+) neurons was associated with the corresponding increase in calbindin(+) neurons in the proximal colon. These findings suggest that neuronal subtype conversion may occur in the absence of PCGF1 and that epigenetic mechanism is primarily involved in specification of some enteric neuron subtypes. This article is protected by copyright. All rights reserved.", "classifications": [ { "id": "JPMJCR2021", "label": "JPMJCR2021", "researcher": "Hideki Enomoto", "type": "grant" }, { "id": "Enomoto", "label": "Group Enomoto", "parent": "Enomoto", "type": "group" }, { "id": "Enomoto", "label": "Team Enomoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Bayu Pratama", "last_name": "Putra", "name": null }, { "creator_type": "author", "first_name": "Keisuke", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Carla", "last_name": "Cirillo", "name": null }, { "creator_type": "author", "first_name": "Mukhamad", "last_name": "Sunardi", "name": null }, { "creator_type": "author", "first_name": "Haruhiko", "last_name": "Koseki", "name": null }, { "creator_type": "author", "first_name": "Toshihiro", "last_name": "Uesaka", "name": null }, { "creator_type": "author", "first_name": "Hideki", "last_name": "Enomoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/dgd.12880" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "37452641" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Enteric Nervous System", "descriptor_ui": "D017615", "major_topic": true }, { "descriptor": "Epigenesis, Genetic", "descriptor_ui": "D044127", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": true }, { "descriptor": "Polycomb Repressive Complex 1", "descriptor_ui": "D063150", "major_topic": false }, { "descriptor": "Transcription Factors", "descriptor_ui": "D014157", "major_topic": false } ], "publication": { "conference_name": null, "date": "2023 Jul 15", "date_precision": "day", "issue": "", "normalized_date": "2023-07-15", "pages": "", "proceedings_title": null, "publisher": "", "title": "Development, growth & differentiation", "volume": "", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Pcgf1 gene disruption reveals primary involvement of epigenetic mechanism in neuronal subtype specification in the enteric nervous system.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "KRAS is the most commonly mutated oncogene in advanced, non-squamous, non-small cell lung cancer (NSCLC) in Western countries. Of the various KRAS mutants, KRAS G12C is the most common variant (~40%), representing 10-13% of advanced non-squamous NSCLC. Recent regulatory approvals of the KRAS(G12C)-selective inhibitors sotorasib and adagrasib for patients with advanced or metastatic NSCLC harboring KRASG12C have transformed KRAS into a druggable target. In this review, we explore the evolving role of KRAS from a prognostic to a predictive biomarker in advanced NSCLC, discussing KRAS G12C biology, real-world prevalence, clinical relevance of co-mutations, and approaches to molecular testing. Real-world evidence demonstrates significant geographic differences in KRAS G12C prevalence (8.9-19.5% in the US, 9.3-18.4% in Europe, 6.9-9.0% in Latin America, and 1.4-4.3% in Asia) in advanced NSCLC. Additionally, the body of clinical data pertaining to KRAS G12C co-mutations such as STK11, KEAP1, and TP53 is increasing. In real-world evidence, KRAS G12C-mutant NSCLC was associated with STK11, KEAP1, and TP53 co-mutations in 10.3-28.0%, 6.3-23.0%, and 17.8-50.0% of patients, respectively. Whilst sotorasib and adagrasib are currently approved for use in the second-line setting and beyond for patients with advanced/metastatic NSCLC, testing and reporting of the KRAS G12C variant should be included in routine biomarker testing prior to first-line therapy. KRAS G12C test results should be clearly documented in patients' health records for actionability at progression. Where available, next-generation sequencing is recommended to facilitate simultaneous testing of potentially actionable biomarkers in a single run to conserve tissue. Results from molecular testing should inform clinical decisions in treating patients with KRAS G12C-mutated advanced NSCLC.", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Tony Kiat Hon", "last_name": "Lim", "name": null }, { "creator_type": "author", "first_name": "Ferdinandos", "last_name": "Skoulidis", "name": null }, { "creator_type": "author", "first_name": "Keith M.", "last_name": "Kerr", "name": null }, { "creator_type": "author", "first_name": "Myung-Ju", "last_name": "Ahn", "name": null }, { "creator_type": "author", "first_name": "Joshua R.", "last_name": "Kapp", "name": null }, { "creator_type": "author", "first_name": "Fernando A.", "last_name": "Soares", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.lungcan.2023.107293" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "37683526" } }, "mesh": [ { "descriptor": "Acetonitriles", "descriptor_ui": "D000097", "major_topic": false }, { "descriptor": "Carcinoma, Non-Small-Cell Lung", "descriptor_ui": "D002289", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Kelch-Like ECH-Associated Protein 1", "descriptor_ui": "D000072019", "major_topic": false }, { "descriptor": "Lung Neoplasms", "descriptor_ui": "D008175", "major_topic": true }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": false }, { "descriptor": "NF-E2-Related Factor 2", "descriptor_ui": "D051267", "major_topic": false }, { "descriptor": "Piperazines", "descriptor_ui": "D010879", "major_topic": false }, { "descriptor": "Prevalence", "descriptor_ui": "D015995", "major_topic": false }, { "descriptor": "Proto-Oncogene Proteins p21(ras)", "descriptor_ui": "D016283", "major_topic": false }, { "descriptor": "Pyrimidines", "descriptor_ui": "D011743", "major_topic": false } ], "publication": { "conference_name": null, "date": "2023 Jul 13", "date_precision": "day", "issue": "", "normalized_date": "2023-07-13", "pages": "107293", "proceedings_title": null, "publisher": "", "title": "Lung cancer (Amsterdam, Netherlands)", "volume": "184", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "KRAS G12C in advanced NSCLC: Prevalence, co-mutations, and testing.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The incidence of second primary neoplasms arising in the skin reconstructive flap (SNAF) is increasing because of the increase in head and neck flap reconstruction and cancer survival. Prognosis, optimal treatment, and their clinicopathological-genetic features are under debate and are difficult to diagnose. We retrospectively reviewed SNAFs based on a single center's experience over 20 years. Medical records and specimens of 21 patients with SNAF who underwent biopsies between April 2000 and April 2020 at our institute were retrospectively analyzed. Definite squamous cell carcinoma and the remaining neoplastic lesions were subclassified as flap cancer (FC) and precancerous lesions (PLs), respectively. Immunohistochemical studies focused on p53 and p16. TP53 sequencing was conducted using next-generation sequencing. Seven and 14 patients had definite FC and PL, respectively. The mean number of biopsies/latency intervals was 2.0 times/114 months and 2.5 times/108 months for FC and PL, respectively. All lesions were grossly exophytic and accompanied by inflamed stroma. In FC and PL, the incidences of altered p53 types were 43% and 29%, respectively, and those of positive p16 stains were 57% and 64%, respectively. Mutation of TP53 in FC and PL were 17% and 29%, respectively. All except one patient with FC under long-term immunosuppressive therapy survived in this study. SNAFs are grossly exophytic tumors with an inflammatory background and show a relatively low altered p53 and TP53 rate and a high p16 positivity rate. They are slow-growing neoplasms with good prognoses. Diagnosis is often difficult; therefore, repeated or excisional biopsy of the lesion may be desirable.", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Kohtaro", "last_name": "Eguchi", "name": null }, { "creator_type": "author", "first_name": "Kenya", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Yoshitaka", "last_name": "Honma", "name": null }, { "creator_type": "author", "first_name": "Eijitsu", "last_name": "Ryo", "name": null }, { "creator_type": "author", "first_name": "Airi", "last_name": "Sakyo", "name": null }, { "creator_type": "author", "first_name": "Kazuki", "last_name": "Yokoyama", "name": null }, { "creator_type": "author", "first_name": "Takane", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Aihara", "name": null }, { "creator_type": "author", "first_name": "Azusa", "last_name": "Sakai", "name": null }, { "creator_type": "author", "first_name": "Yoshifumi", "last_name": "Matsumoto", "name": null }, { "creator_type": "author", "first_name": "Toshihiko", "last_name": "Sakai", "name": null }, { "creator_type": "author", "first_name": "Go", "last_name": "Omura", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null }, { "creator_type": "author", "first_name": "Seiichi", "last_name": "Yoshimoto", "name": null }, { "creator_type": "author", "first_name": "Taisuke", "last_name": "Mori", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41598-023-38122-9" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "37433786" } }, "mesh": [ { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Head", "descriptor_ui": "D006257", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Neck", "descriptor_ui": "D009333", "major_topic": false }, { "descriptor": "Neoplasms, Second Primary", "descriptor_ui": "D016609", "major_topic": true }, { "descriptor": "Pregnancy", "descriptor_ui": "D011247", "major_topic": false }, { "descriptor": "Retrospective Studies", "descriptor_ui": "D012189", "major_topic": false }, { "descriptor": "Tumor Suppressor Protein p53", "descriptor_ui": "D016159", "major_topic": false } ], "publication": { "conference_name": null, "date": "2023 Jul 11", "date_precision": "day", "issue": "1", "normalized_date": "2023-07-11", "pages": "11214", "proceedings_title": null, "publisher": "", "title": "Scientific reports", "volume": "13", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Clinical and pathological features of second primary neoplasms arising in head and neck reconstructive skin flaps.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Naked mole-rats (NMRs) have exceptional longevity and are resistant to age-related physiological decline and diseases. Given the role of cellular senescence in aging, we postulated that NMRs possess unidentified species-specific mechanisms to prevent senescent cell accumulation. Here, we show that upon induction of cellular senescence, NMR fibroblasts underwent delayed and progressive cell death that required activation of the INK4a-retinoblastoma protein (RB) pathway (termed \"INK4a-RB cell death\"), a phenomenon not observed in mouse fibroblasts. Naked mole-rat fibroblasts uniquely accumulated serotonin and were inherently vulnerable to hydrogen peroxide (H(2) O(2) ). After activation of the INK4a-RB pathway, NMR fibroblasts increased monoamine oxidase levels, leading to serotonin oxidization and H(2) O(2) production, which resulted in increased intracellular oxidative damage and cell death activation. In the NMR lung, induction of cellular senescence caused delayed, progressive cell death mediated by monoamine oxidase activation, thereby preventing senescent cell accumulation, consistent with in vitro results. The present findings indicate that INK4a-RB cell death likely functions as a natural senolytic mechanism in NMRs, providing an evolutionary rationale for senescent cell removal as a strategy to resist aging.", "classifications": [ { "id": "Yamamoto", "label": "Group Yamamoto", "parent": "Toyoshima", "type": "group" }, { "id": "Toyoshima", "label": "Team Toyoshima", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yoshimi", "last_name": "Kawamura", "name": null }, { "creator_type": "author", "first_name": "Kaori", "last_name": "Oka", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Semba", "name": null }, { "creator_type": "author", "first_name": "Mayuko", "last_name": "Takamori", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Sugiura", "name": null }, { "creator_type": "author", "first_name": "Riyo", "last_name": "Yamasaki", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Chujo", "name": null }, { "creator_type": "author", "first_name": "Mari", "last_name": "Nagase", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Oiwa", "name": null }, { "creator_type": "author", "first_name": "Shusuke", "last_name": "Fujioka", "name": null }, { "creator_type": "author", "first_name": "Sayuri", "last_name": "Homma", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Yamamura", "name": null }, { "creator_type": "author", "first_name": "Shingo", "last_name": "Miyawaki", "name": null }, { "creator_type": "author", "first_name": "Minoru", "last_name": "Narita", "name": null }, { "creator_type": "author", "first_name": "Takaichi", "last_name": "Fukuda", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Sakai", "name": null }, { "creator_type": "author", "first_name": "Takatsugu", "last_name": "Ishimoto", "name": null }, { "creator_type": "author", "first_name": "Kazuhito", "last_name": "Tomizawa", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Suematsu", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Hidemasa", "last_name": "Bono", "name": null }, { "creator_type": "author", "first_name": "Hideyuki", "last_name": "Okano", "name": null }, { "creator_type": "author", "first_name": "Kyoko", "last_name": "Miura", "name": null } ], "identifiers": { "doi": { "normalized": "10.15252/embj.2022111133" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "37431790" } }, "mesh": [ { "descriptor": "Aging", "descriptor_ui": "D000375", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Death", "descriptor_ui": "D016923", "major_topic": false }, { "descriptor": "Cellular Senescence", "descriptor_ui": "D016922", "major_topic": true }, { "descriptor": "Cyclin-Dependent Kinase Inhibitor p16", "descriptor_ui": "D019941", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mole Rats", "descriptor_ui": "D019577", "major_topic": false }, { "descriptor": "Serotonin", "descriptor_ui": "D012701", "major_topic": true } ], "publication": { "conference_name": null, "date": "2023 Jul 11", "date_precision": "day", "issue": "", "normalized_date": "2023-07-11", "pages": "e111133", "proceedings_title": null, "publisher": "", "title": "The EMBO journal", "volume": "", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Cellular senescence induction leads to progressive cell death via the INK4a-RB pathway in naked mole-rats.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "A growing community is constructing a next-generation file format (NGFF) for bioimaging to overcome problems of scalability and heterogeneity. Organized by the Open Microscopy Environment (OME), individuals and institutes across diverse modalities facing these problems have designed a format specification process (OME-NGFF) to address these needs. This paper brings together a wide range of those community members to describe the cloud-optimized format itself-OME-Zarr-along with tools and data resources available today to increase FAIR access and remove barriers in the scientific process. The current momentum offers an opportunity to unify a key component of the bioimaging domain-the file format that underlies so many personal, institutional, and global data management and analysis tasks.", "classifications": [ { "id": "JPMJCR1926", "label": "JPMJCR1926", "researcher": "Hironobu Fujiwara", "type": "grant" }, { "id": "Fujiwara", "label": "Group Fujiwara", "parent": "Fujiwara", "type": "group" }, { "id": "Onami", "label": "Group Onami", "parent": "Fujiwara", "type": "group" }, { "id": "Fujiwara", "label": "Team Fujiwara", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Josh", "last_name": "Moore", "name": null }, { "creator_type": "author", "first_name": "Daniela", "last_name": "Basurto-Lozada", "name": null }, { "creator_type": "author", "first_name": "Sebastien", "last_name": "Besson", "name": null }, { "creator_type": "author", "first_name": "John", "last_name": "Bogovic", "name": null }, { "creator_type": "author", "first_name": "Jordao", "last_name": "Bragantini", "name": null }, { "creator_type": "author", "first_name": "Eva M.", "last_name": "Brown", "name": null }, { "creator_type": "author", "first_name": "Jean-Marie", "last_name": "Burel", "name": null }, { "creator_type": "author", "first_name": "Xavier", "last_name": "Casas Moreno", "name": null }, { "creator_type": "author", "first_name": "Gustavo", "last_name": "de Medeiros", "name": null }, { "creator_type": "author", "first_name": "Erin E.", "last_name": "Diel", "name": null }, { "creator_type": "author", "first_name": "David", "last_name": "Gault", "name": null }, { "creator_type": "author", "first_name": "Satrajit S.", "last_name": "Ghosh", "name": null }, { "creator_type": "author", "first_name": "Ilan", "last_name": "Gold", "name": null }, { "creator_type": "author", "first_name": "Yaroslav O.", "last_name": "Halchenko", "name": null }, { "creator_type": "author", "first_name": "Matthew", "last_name": "Hartley", "name": null }, { "creator_type": "author", "first_name": "Dave", "last_name": "Horsfall", "name": null }, { "creator_type": "author", "first_name": "Mark S.", "last_name": "Keller", "name": null }, { "creator_type": "author", "first_name": "Mark", "last_name": "Kittisopikul", "name": null }, { "creator_type": "author", "first_name": "Gabor", "last_name": "Kovacs", "name": null }, { "creator_type": "author", "first_name": "Aybuke", "last_name": "Kupcu Yoldas", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Kyoda", "name": null }, { "creator_type": "author", "first_name": "Albane", "last_name": "le Tournoulx de la Villegeorges", "name": null }, { "creator_type": "author", "first_name": "Tong", "last_name": "Li", "name": null }, { "creator_type": "author", "first_name": "Prisca", "last_name": "Liberali", "name": null }, { "creator_type": "author", "first_name": "Dominik", "last_name": "Lindner", "name": null }, { "creator_type": "author", "first_name": "Melissa", "last_name": "Linkert", "name": null }, { "creator_type": "author", "first_name": "Joel", "last_name": "Luthi", "name": null }, { "creator_type": "author", "first_name": "Jeremy", "last_name": "Maitin-Shepard", "name": null }, { "creator_type": "author", "first_name": "Trevor", "last_name": "Manz", "name": null }, { "creator_type": "author", "first_name": "Luca", "last_name": "Marconato", "name": null }, { "creator_type": "author", "first_name": "Matthew", "last_name": "McCormick", "name": null }, { "creator_type": "author", "first_name": "Merlin", "last_name": "Lange", "name": null }, { "creator_type": "author", "first_name": "Khaled", "last_name": "Mohamed", "name": null }, { "creator_type": "author", "first_name": "William", "last_name": "Moore", "name": null }, { "creator_type": "author", "first_name": "Nils", "last_name": "Norlin", "name": null }, { "creator_type": "author", "first_name": "Wei", "last_name": "Ouyang", "name": null }, { "creator_type": "author", "first_name": "Bugra", "last_name": "Ozdemir", "name": null }, { "creator_type": "author", "first_name": "Giovanni", "last_name": "Palla", "name": null }, { "creator_type": "author", "first_name": "Constantin", "last_name": "Pape", "name": null }, { "creator_type": "author", "first_name": "Lucas", "last_name": "Pelkmans", "name": null }, { "creator_type": "author", "first_name": "Tobias", "last_name": "Pietzsch", "name": null }, { "creator_type": "author", "first_name": "Stephan", "last_name": "Preibisch", "name": null }, { "creator_type": "author", "first_name": "Martin", "last_name": "Prete", "name": null }, { "creator_type": "author", "first_name": "Norman", "last_name": "Rzepka", "name": null }, { "creator_type": "author", "first_name": "Sameeul", "last_name": "Samee", "name": null }, { "creator_type": "author", "first_name": "Nicholas", "last_name": "Schaub", "name": null }, { "creator_type": "author", "first_name": "Hythem", "last_name": "Sidky", "name": null }, { "creator_type": "author", "first_name": "Ahmet Can", "last_name": "Solak", "name": null }, { "creator_type": "author", "first_name": "David R.", "last_name": "Stirling", "name": null }, { "creator_type": "author", "first_name": "Jonathan", "last_name": "Striebel", "name": null }, { "creator_type": "author", "first_name": "Christian", "last_name": "Tischer", "name": null }, { "creator_type": "author", "first_name": "Daniel", "last_name": "Toloudis", "name": null }, { "creator_type": "author", "first_name": "Isaac", "last_name": "Virshup", "name": null }, { "creator_type": "author", "first_name": "Petr", "last_name": "Walczysko", "name": null }, { "creator_type": "author", "first_name": "Alan M.", "last_name": "Watson", "name": null }, { "creator_type": "author", "first_name": "Erin", "last_name": "Weisbart", "name": null }, { "creator_type": "author", "first_name": "Frances", "last_name": "Wong", "name": null }, { "creator_type": "author", "first_name": "Kevin A.", "last_name": "Yamauchi", "name": null }, { "creator_type": "author", "first_name": "Omer", "last_name": "Bayraktar", "name": null }, { "creator_type": "author", "first_name": "Beth A.", "last_name": "Cimini", "name": null }, { "creator_type": "author", "first_name": "Nils", "last_name": "Gehlenborg", "name": null }, { "creator_type": "author", "first_name": "Muzlifah", "last_name": "Haniffa", "name": null }, { "creator_type": "author", "first_name": "Nathan", "last_name": "Hotaling", "name": null }, { "creator_type": "author", "first_name": "Shuichi", "last_name": "Onami", "name": null }, { "creator_type": "author", "first_name": "Loic A.", "last_name": "Royer", "name": null }, { "creator_type": "author", "first_name": "Stephan", "last_name": "Saalfeld", "name": null }, { "creator_type": "author", "first_name": "Oliver", "last_name": "Stegle", "name": null }, { "creator_type": "author", "first_name": "Fabian J.", "last_name": "Theis", "name": null }, { "creator_type": "author", "first_name": "Jason R.", "last_name": "Swedlow", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/s00418-023-02209-1" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "37428210" } }, "mesh": [ { "descriptor": "Community Support", "descriptor_ui": "D000091443", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Microscopy", "descriptor_ui": "D008853", "major_topic": true }, { "descriptor": "Software", "descriptor_ui": "D012984", "major_topic": true } ], "publication": { "conference_name": null, "date": "2023 Jul 10", "date_precision": "day", "issue": "", "normalized_date": "2023-07-10", "pages": "", "proceedings_title": null, "publisher": "", "title": "Histochemistry and cell biology", "volume": "", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "OME-Zarr: a cloud-optimized bioimaging file format with international community support.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Plants can regenerate their bodies via de novo establishment of shoot apical meristems (SAMs) from pluripotent callus. Only a small fraction of callus cells is eventually specified into SAMs but the molecular mechanisms underlying fate specification remain obscure. The expression of WUSCHEL (WUS) is an early hallmark of SAM fate acquisition. Here, we show that a WUS paralog, WUSCHEL-RELATED HOMEOBOX 13 (WOX13), negatively regulates SAM formation from callus in Arabidopsis thaliana. WOX13 promotes non-meristematic cell fate via transcriptional repression of WUS and other SAM regulators and activation of cell wall modifiers. Our Quartz-Seq2–based single cell transcriptome revealed that WOX13 plays key roles in determining cellular identity of callus cell population. We propose that reciprocal inhibition between WUS and WOX13 mediates critical cell fate determination in pluripotent cell population, which has a major impact on regeneration efficiency.", "classifications": [ { "id": "JPMJCR1926", "label": "JPMJCR1926", "researcher": "Hironobu Fujiwara", "type": "grant" } ], "creators": [ { "creator_type": "author", "first_name": "Nao", "last_name": "Ogura", "name": null }, { "creator_type": "author", "first_name": "Yohei", "last_name": "Sasagawa", "name": null }, { "creator_type": "author", "first_name": "Tasuku", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Toshiaki", "last_name": "Tameshige", "name": null }, { "creator_type": "author", "first_name": "Satomi", "last_name": "Kawai", "name": null }, { "creator_type": "author", "first_name": "Masaki", "last_name": "Sano", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Doll", "name": null }, { "creator_type": "author", "first_name": "Akira", "last_name": "Iwase", "name": null }, { "creator_type": "author", "first_name": "Ayako", "last_name": "Kawamura", "name": null }, { "creator_type": "author", "first_name": "Takamasa", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Itoshi", "last_name": "Nikaido", "name": null }, { "creator_type": "author", "first_name": "Keiko", "last_name": "Sugimoto", "name": null }, { "creator_type": "author", "first_name": "Momoko", "last_name": "Ikeuchi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1126/sciadv.adg6983" }, "pmcid": { "normalized": null }, "pmid": { "normalized": null } }, "mesh": [], "publication": { "conference_name": null, "date": "2023-07-07", "date_precision": "day", "issue": "27", "normalized_date": "2023-07-07", "pages": "eadg6983", "proceedings_title": null, "publisher": "American Association for the Advancement of Science", "title": "Science Advances", "volume": "9", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "WUSCHEL-RELATED HOMEOBOX 13 suppresses de novo shoot regeneration via cell fate control of pluripotent callus", "url": "https://www.science.org/doi/10.1126/sciadv.adg6983", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The Alcohol, Smoking and Substance Involvement Screening Test (ASSIST) is an instrument to screen substance-use-related health risks. However, little is known whether the ASSIST could be further shortened while remaining psychometrically sound across different countries, languages, gender identities, and sexual-orientation-based groups. The study aimed to validate a shortened 11-item ASSIST (ASSIST-11). Using the International Sex Survey data, 82,243 participants (M (age) = 32.39 years) across 42 countries and 26 languages completed questions from the ASSIST-11 regarding gender identity, sexual orientation, and other information. Confirmatory factor analysis (CFA) and multigroup CFA (MGCFA) evaluated the ASSIST-11's structure and tested measurement invariance across groups. Cronbach's alpha and McDonald's omega were used to examine the internal consistency. Cohen's d and independent t-tests were used to examine known-group validity. The ASSIST-11 was unidimensional across countries, languages, age groups, gender identities (i.e., men, women, and gender-diverse individuals), and sexual orientations (i.e., heterosexual and sexual minority individuals). Cronbach's alpha was 0.63 and McDonald's omega was 0.68 for the ASSIST-11. Known-group validity was supported by Cohen's d (range between 0.23 and 0.40) with significant differences (p-values<0.001). The ASSIST-11 is a modified instrument with a unidimensional factor structure across different languages, age groups, countries, gender identities, and sexual orientations. The low internal consistency of the ASSIST-11 might be acceptable as it assesses a broad concept (i.e., use of several different substances). Healthcare providers and researchers may use the ASSIST-11 to quickly assess substance-use information from general populations and evaluate the need to follow up with more detailed questions about substance use.", "classifications": [ { "id": "Fujiwara", "label": "Group Fujiwara", "parent": "Fujiwara", "type": "group" }, { "id": "Fujiwara", "label": "Team Fujiwara", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Chih-Ting", "last_name": "Lee", "name": null }, { "creator_type": "author", "first_name": "Chung-Ying", "last_name": "Lin", "name": null }, { "creator_type": "author", "first_name": "Monika", "last_name": "Koos", "name": null }, { "creator_type": "author", "first_name": "Lena", "last_name": "Nagy", "name": null }, { "creator_type": "author", "first_name": "Shane W.", "last_name": "Kraus", "name": null }, { "creator_type": "author", "first_name": "Zsolt", "last_name": "Demetrovics", "name": null }, { "creator_type": "author", "first_name": "Marc N.", "last_name": "Potenza", "name": null }, { "creator_type": "author", "first_name": "Rafael", "last_name": "Ballester-Arnal", "name": null }, { "creator_type": "author", "first_name": "Dominik", "last_name": "Batthyany", "name": null }, { "creator_type": "author", "first_name": "Sophie", "last_name": "Bergeron", "name": null }, { "creator_type": "author", "first_name": "Joel", "last_name": "Billieux", "name": null }, { "creator_type": "author", "first_name": "Julius", "last_name": "Burkauskas", "name": null }, { "creator_type": "author", "first_name": "Georgina", "last_name": "Cardenas-Lopez", "name": null }, { "creator_type": "author", "first_name": "Joana", "last_name": "Carvalho", "name": null }, { "creator_type": "author", "first_name": "Jesus", "last_name": "Castro-Calvo", "name": null }, { "creator_type": "author", "first_name": "Lijun", "last_name": "Chen", "name": null }, { "creator_type": "author", "first_name": "Giacomo", "last_name": "Ciocca", "name": null }, { "creator_type": "author", "first_name": "Ornella", "last_name": "Corazza", "name": null }, { "creator_type": "author", "first_name": "Rita I.", "last_name": "Csako", "name": null }, { "creator_type": "author", "first_name": "David P.", "last_name": "Fernandez", "name": null }, { "creator_type": "author", "first_name": "Elaine F.", "last_name": "Fernandez", "name": null }, { "creator_type": "author", "first_name": "Hironobu", "last_name": "Fujiwara", "name": null }, { "creator_type": "author", "first_name": "Johannes", "last_name": "Fuss", "name": null }, { "creator_type": "author", "first_name": "Roman", "last_name": "Gabrhelik", "name": null }, { "creator_type": "author", "first_name": "Ateret", "last_name": "Gewirtz-Meydan", "name": null }, { "creator_type": "author", "first_name": "Biljana", "last_name": "Gjoneska", "name": null }, { "creator_type": "author", "first_name": "Mateusz", "last_name": "Gola", "name": null }, { "creator_type": "author", "first_name": "Joshua B.", "last_name": "Grubbs", "name": null }, { "creator_type": "author", "first_name": "Hashim T.", "last_name": "Hashim", "name": null }, { "creator_type": "author", "first_name": "Md Saiful", "last_name": "Islam", "name": null }, { "creator_type": "author", "first_name": "Mustafa", "last_name": "Ismail", "name": null }, { "creator_type": "author", "first_name": "Martha", "last_name": "Jimenez-Martinez", "name": null }, { "creator_type": "author", "first_name": "Tanja", "last_name": "Jurin", "name": null }, { "creator_type": "author", "first_name": "Ondrej", "last_name": "Kalina", "name": null }, { "creator_type": "author", "first_name": "Verena", "last_name": "Klein", "name": null }, { "creator_type": "author", "first_name": "Andras", "last_name": "Kolto", "name": null }, { "creator_type": "author", "first_name": "Sang-Kyu", "last_name": "Lee", "name": null }, { "creator_type": "author", "first_name": "Karol", "last_name": "Lewczuk", "name": null }, { "creator_type": "author", "first_name": "Christine", "last_name": "Lochner", "name": null }, { "creator_type": "author", "first_name": "Silvia", "last_name": "Lopez-Alvarado", "name": null }, { "creator_type": "author", "first_name": "Katerina", "last_name": "Lukavska", "name": null }, { "creator_type": "author", "first_name": "Percy", "last_name": "Mayta-Tristan", "name": null }, { "creator_type": "author", "first_name": "Ionut", "last_name": "Milea", "name": null }, { "creator_type": "author", "first_name": "Dan J.", "last_name": "Miller", "name": null }, { "creator_type": "author", "first_name": "Olga", "last_name": "Orosova", "name": null }, { "creator_type": "author", "first_name": "Gabor", "last_name": "Orosz", "name": null }, { "creator_type": "author", "first_name": "Fernando P.", "last_name": "Ponce", "name": null }, { "creator_type": "author", "first_name": "Gonzalo R.", "last_name": "Quintana", "name": null }, { "creator_type": "author", "first_name": "Gabriel C. Quintero", "last_name": "Garzola", "name": null }, { "creator_type": "author", "first_name": "Jano", "last_name": "Ramos-Diaz", "name": null }, { "creator_type": "author", "first_name": "Kevin", "last_name": "Rigaud", "name": null }, { "creator_type": "author", "first_name": "Ann", "last_name": "Rousseau", "name": null }, { "creator_type": "author", "first_name": "Marco De Tubino", "last_name": "Scanavino", "name": null }, { "creator_type": "author", "first_name": "Marion K.", "last_name": "Schulmeyer", "name": null }, { "creator_type": "author", "first_name": "Pratap", "last_name": "Sharan", "name": null }, { "creator_type": "author", "first_name": "Mami", "last_name": "Shibata", "name": null }, { "creator_type": "author", "first_name": "Sheikh", "last_name": "Shoib", "name": null }, { "creator_type": "author", "first_name": "Vera", "last_name": "Sigre-Leiros", "name": null }, { "creator_type": "author", "first_name": "Luke", "last_name": "Sniewski", "name": null }, { "creator_type": "author", "first_name": "Ognen", "last_name": "Spasovski", "name": null }, { "creator_type": "author", "first_name": "Vesta", "last_name": "Steibliene", "name": null }, { "creator_type": "author", "first_name": "Dan J.", "last_name": "Stein", "name": null }, { "creator_type": "author", "first_name": "Julian", "last_name": "Strizek", "name": null }, { "creator_type": "author", "first_name": "Berk C.", "last_name": "Unsal", "name": null }, { "creator_type": "author", "first_name": "Marie-Pier", "last_name": "Vaillancourt-Morel", "name": null }, { "creator_type": "author", "first_name": "Marie Claire", "last_name": "Van Hout", "name": null }, { "creator_type": "author", "first_name": "Beata", "last_name": "Bothe", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.jpsychires.2023.06.033" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "37453212" } }, "mesh": [ { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Cross-Cultural Comparison", "descriptor_ui": "D003431", "major_topic": true }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Gender Identity", "descriptor_ui": "D005783", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Psychometrics", "descriptor_ui": "D011594", "major_topic": false }, { "descriptor": "Reproducibility of Results", "descriptor_ui": "D015203", "major_topic": false }, { "descriptor": "Smoking", "descriptor_ui": "D012907", "major_topic": false }, { "descriptor": "Substance-Related Disorders", "descriptor_ui": "D019966", "major_topic": true }, { "descriptor": "Surveys and Questionnaires", "descriptor_ui": "D011795", "major_topic": false } ], "publication": { "conference_name": null, "date": "2023 Jul 6", "date_precision": "day", "issue": "", "normalized_date": "2023-07-06", "pages": "16-27", "proceedings_title": null, "publisher": "", "title": "Journal of psychiatric research", "volume": "165", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "The eleven-item Alcohol, Smoking and Substance Involvement Screening Test (ASSIST-11): Cross-cultural psychometric evaluation across 42 countries.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "A line illumination Raman microscope extracts the underlying spatial and spectral information of a sample, typically a few hundred times faster than raster scanning. This makes it possible to measure a wide range of biological samples such as cells and tissues - that only allow modest intensity illumination to prevent potential damage - within feasible time frame. However, a non-uniform intensity distribution of laser line illumination may induce some artifacts in the data and lower the accuracy of machine learning models trained to predict sample class membership. Here, using cancerous and normal human thyroid follicular epithelial cell lines, FTC-133 and Nthy-ori 3-1 lines, whose Raman spectral difference is not so large, we show that the standard pre-processing of spectral analyses widely used for raster scanning microscopes introduced some artifacts. To address this issue, we proposed a detrending scheme based on random forest regression, a nonparametric model-free machine learning algorithm, combined with a position-dependent wavenumber calibration scheme along the illumination line. It was shown that the detrending scheme minimizes the artifactual biases arising from non-uniform laser sources and significantly enhances the differentiability of the sample states, i.e., cancerous or normal epithelial cells, compared to the standard pre-processing scheme.", "classifications": [ { "id": "Fujita", "label": "Group Fujita", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Abdul Halim", "last_name": "Bhuiyan", "name": null }, { "creator_type": "author", "first_name": "Jean-Emmanuel", "last_name": "Clement", "name": null }, { "creator_type": "author", "first_name": "Zannatul", "last_name": "Ferdous", "name": null }, { "creator_type": "author", "first_name": "Kentaro", "last_name": "Mochizuki", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Tabata", "name": null }, { "creator_type": "author", "first_name": "James Nicholas", "last_name": "Taylor", "name": null }, { "creator_type": "author", "first_name": "Yasuaki", "last_name": "Kumamoto", "name": null }, { "creator_type": "author", "first_name": "Yoshinori", "last_name": "Harada", "name": null }, { "creator_type": "author", "first_name": "Thomas", "last_name": "Bocklitz", "name": null }, { "creator_type": "author", "first_name": "Katsumasa", "last_name": "Fujita", "name": null }, { "creator_type": "author", "first_name": "Tamiki", "last_name": "Komatsuzaki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1039/d3an00516j" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "37403759" } }, "mesh": [ { "descriptor": "Algorithms", "descriptor_ui": "D000465", "major_topic": false }, { "descriptor": "Calibration", "descriptor_ui": "D002138", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Light", "descriptor_ui": "D008027", "major_topic": false }, { "descriptor": "Lighting", "descriptor_ui": "D008029", "major_topic": true }, { "descriptor": "Microscopy", "descriptor_ui": "D008853", "major_topic": true }, { "descriptor": "Spectrum Analysis, Raman", "descriptor_ui": "D013059", "major_topic": false } ], "publication": { "conference_name": null, "date": "2023 Jul 5", "date_precision": "day", "issue": "", "normalized_date": "2023-07-05", "pages": "", "proceedings_title": null, "publisher": "", "title": "The Analyst", "volume": "", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Differentiability of cell types enhanced by detrending a non-homogeneous pattern in a line-illumination Raman microscope.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "CONTEXT: Insulin clearance is implicated in regulation of glucose homeostasis independently of insulin sensitivity and insulin secretion. OBJECTIVE: To understand the relation between blood glucose and insulin sensitivity, secretion, and clearance. METHODS: We performed a hyperglycemic clamp, a hyperinsulinemic-euglycemic clamp, and an oral glucose tolerance test (OGTT) in 47, 16, and 49 subjects with normal glucose tolerance (NGT), impaired glucose tolerance (IGT), and type 2 diabetes mellitus (T2DM), respectively. Mathematical analyses were retrospectively performed on this dataset. RESULTS: The disposition index (DI), defined as the product of insulin sensitivity and secretion, showed a weak correlation with blood glucose levels, especially in IGT (r=0.04; 95% CI,-0.63-0.44). However, an equation relating DI, insulin clearance, and blood glucose levels was well conserved regardless of the extent of glucose intolerance. As a measure of the effect of insulin, we developed an index, designated \"disposition index/clearance,\" (DI/cle) that is based on this equation and corresponds to DI divided by the square of insulin clearance. DI/cle was not impaired in IGT compared with NGT, possibly as a result of a decrease in insulin clearance in response to a reduction in DI, whereas it was impaired in T2DM relative to IGT. Moreover, DI/cle estimated from a hyperinsulinemic-euglycemic clamp, OGTT, or a fasting blood test were significantly correlated with that estimated from two clamp tests (r=0.52; 95% CI,0.37-0.64, r=0.43; 95% CI,0.24-0.58, and r=0.54; 95% CI,0.38-0.68, respectively). CONCLUSIONS: DI/cle can serve as a new indicator for the trajectory of changes in glucose tolerance.", "classifications": [ { "id": "JPMJCR2123", "label": "JPMJCR2123", "researcher": "Shinya Kuroda", "type": "grant" }, { "id": "Kuroda", "label": "Group Kuroda", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Hikaru", "last_name": "Sugimoto", "name": null }, { "creator_type": "author", "first_name": "Ken-Ichi", "last_name": "Hironaka", "name": null }, { "creator_type": "author", "first_name": "Tomoko", "last_name": "Yamada", "name": null }, { "creator_type": "author", "first_name": "Kazuhiko", "last_name": "Sakaguchi", "name": null }, { "creator_type": "author", "first_name": "Wataru", "last_name": "Ogawa", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Kuroda", "name": null } ], "identifiers": { "doi": { "normalized": "10.1210/clinem/dgad392" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "37406246" } }, "mesh": [ { "descriptor": "Blood Glucose", "descriptor_ui": "D001786", "major_topic": false }, { "descriptor": "Diabetes Mellitus, Type 2", "descriptor_ui": "D003924", "major_topic": true }, { "descriptor": "Glucose", "descriptor_ui": "D005947", "major_topic": false }, { "descriptor": "Glucose Intolerance", "descriptor_ui": "D018149", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Insulin", "descriptor_ui": "D007328", "major_topic": false }, { "descriptor": "Insulin Resistance", "descriptor_ui": "D007333", "major_topic": true }, { "descriptor": "Retrospective Studies", "descriptor_ui": "D012189", "major_topic": false } ], "publication": { "conference_name": null, "date": "2023 Jul 5", "date_precision": "day", "issue": "", "normalized_date": "2023-07-05", "pages": "dgad392", "proceedings_title": null, "publisher": "", "title": "The Journal of clinical endocrinology and metabolism", "volume": "", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "DI/cle, a Measure Consisting of Insulin Sensitivity, Secretion, and Clearance, Captures Diabetic States.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Lodging of cereal crops significantly reduces grain yield and quality, making lodging resistance a prime target for breeding programs. However, lodging resistance among different rice (Oryza sativa L.) cultivars in the field remains largely unknown, as is the relationship between the major properties of culms such as their morphological and mechanical properties. Here, we investigated the morphological and mechanical properties of 12 rice cultivars by considering different internodes within culms. We detected variation in these two traits among cultivars: one set of cultivars had thicker but softer culms (thickness-type), while the other set of cultivars showed stiffer but thinner culms (stiffness-type). We designate this variation as a thickness-stiffness trade-off. We then constructed a mechanical model to dissect the mechanical and/or morphological constraints of rice culms subjected to their own weight (self-weight load). Through modeling, we discovered that ear weight and the morphology of the highest internode were important for reducing deflection, which may be important factors to achieve higher lodging resistance. The mechanical theory devised in this study could be used to predict the deflection of rice culms and may open new avenues for novel mechanics-based breeding techniques.", "classifications": [ { "id": "JPMJCR2121", "label": "JPMJCR2121", "researcher": "Minako Ueda", "type": "grant" } ], "creators": [ { "creator_type": "author", "first_name": "Satoru", "last_name": "Tsugawa", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Shima", "name": null }, { "creator_type": "author", "first_name": "Yukitaka", "last_name": "Ishimoto", "name": null }, { "creator_type": "author", "first_name": "Kazuya", "last_name": "Ishikawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41598-023-37992-3" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "37402826" } }, "mesh": [ { "descriptor": "Edible Grain", "descriptor_ui": "D002523", "major_topic": false }, { "descriptor": "Oryza", "descriptor_ui": "D012275", "major_topic": true }, { "descriptor": "Phenotype", "descriptor_ui": "D010641", "major_topic": false }, { "descriptor": "Plant Breeding", "descriptor_ui": "D000069600", "major_topic": false } ], "publication": { "conference_name": null, "date": "2023 Jul 4", "date_precision": "day", "issue": "1", "normalized_date": "2023-07-04", "pages": "10828", "proceedings_title": null, "publisher": "", "title": "Scientific reports", "volume": "13", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Thickness-stiffness trade-off improves lodging resistance in rice.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Mechanical forces are critical for regulating many biological processes such as cell differentiation, proliferation, and death. Probing the continuously changing molecular force through integrin receptors provides insights into the molecular mechanism of rigidity sensing in cells; however, the force information is still limited. Here, we built a coil-shaped DNA origami (DNA nanospring, NS) as a force sensor that reports the dynamic motion of single integrins as well as the magnitude and orientation of the force through integrins in living cells. We monitored the extension with nanometer accuracy and the orientation of the NS linked with a single integrin by the shape of the fluorescence spots. We used acoustic force spectroscopy to estimate the force–extension curve of the NS and determined the force with an ∼10% force error at a broad detectable range from subpicoNewtons (pN) to ∼50 pN. We found single integrins tethered with the NS moved several tens of nanometers, and the contraction and relaxation speeds were load dependent at less than ∼20 pN but robust over ∼20 pN. Fluctuations of the traction force orientation were suppressed with increasing load. Our assay system is a potentially powerful tool for studying mechanosensing at the molecular level.", "classifications": [ { "id": "JPMJCR2023", "label": "JPMJCR2023", "researcher": "Fumiko Toyoshima", "type": "grant" }, { "id": "Iwaki", "label": "Group Iwaki", "parent": "Toyoshima", "type": "group" }, { "id": "Toyoshima", "label": "Group Toyoshima", "parent": "Toyoshima", "type": "group" }, { "id": "Toyoshima", "label": "Team Toyoshima", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Hitomi", "last_name": "Matsubara", "name": null }, { "creator_type": "author", "first_name": "Hiroki", "last_name": "Fukunaga", "name": null }, { "creator_type": "author", "first_name": "Takahiro", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Keigo", "last_name": "Ikezaki", "name": null }, { "creator_type": "author", "first_name": "Mitsuhiro", "last_name": "Iwaki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/acsnano.2c12545" }, "pmcid": { "normalized": null }, "pmid": { "normalized": null } }, "mesh": [], "publication": { "conference_name": null, "date": "2023-07-02", "date_precision": "day", "issue": "", "normalized_date": "2023-07-02", "pages": "", "proceedings_title": null, "publisher": "American Chemical Society", "title": "ACS Nano", "volume": "", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "A Programmable DNA Origami Nanospring That Reports Dynamics of Single Integrin Motion, Force Magnitude and Force Orientation in Living Cells", "url": "https://doi.org/10.1021/acsnano.2c12545", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: Cryobiopsy is recently being promoted for biopsy of tumors in the lung periphery in precision medicine for lung cancer; the obtained tissue samples have been reported to be more useful compared to those obtained using forceps, because of the larger volume and higher quality. However, the influence of freezing and thawing of tissues when performing cryobiopsy on the results of immunohistochemistry (IHC) has not been completely understood. METHODS: In this study, consecutive patients who underwent diagnostic bronchoscopy with cryobiopsy for peripheral pulmonary lesions (PPLs) at our institution between June 2017 and November 2021 were reviewed retrospectively. Specimens of diagnosed cases of unresectable or recurrent non-small cell lung carcinoma (NSCLC) were selected. We compared the results of IHC assessment for programmed death-ligand 1 (PD-L1), human epidermal growth factor receptor 2 (HER2), and human epidermal growth factor receptor 3 (HER3) in cryobiopsy specimens versus conventional forceps biopsy specimens from the same site in the same procedure. RESULTS: Twenty-four of 40 patients were male (60%). The most frequent histologic type of cancer was adenocarcinoma (n=31, 77.5%), followed by NSCLC (n=4, 10%), squamous cell carcinoma (n=3, 7.5%), and others (n=2, 5%). The concordance rates of the tumor proportion scores (TPSs) for PD-L1, IHC score for HER2 and, IHC scores for HER3 were 85%, 72.5%, and 75%, respectively; the weighted kappa were 0.835, 0.637, and 0.697, respectively. CONCLUSIONS: Freezing and thawing associated with cryobiopsy had virtually no effect on the results of IHC. We suggest that cryobiopsy specimens would therefore be ideal for precision medicine and translational research.", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Kanako", "last_name": "Nishimatsu", "name": null }, { "creator_type": "author", "first_name": "Yuji", "last_name": "Matsumoto", "name": null }, { "creator_type": "author", "first_name": "Jumpei", "last_name": "Kashima", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Imabayashi", "name": null }, { "creator_type": "author", "first_name": "Keigo", "last_name": "Uchimura", "name": null }, { "creator_type": "author", "first_name": "Hideaki", "last_name": "Furuse", "name": null }, { "creator_type": "author", "first_name": "Ken", "last_name": "Masuda", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Shinno", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Okuma", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Goto", "name": null }, { "creator_type": "author", "first_name": "Hidehito", "last_name": "Horinouchi", "name": null }, { "creator_type": "author", "first_name": "Noboru", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Takaaki", "last_name": "Tsuchida", "name": null }, { "creator_type": "author", "first_name": "Yuichiro", "last_name": "Ohe", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null } ], "identifiers": { "doi": { "normalized": "10.21037/tlcr-22-621" }, "pmcid": { "normalized": "PMC10326773" }, "pmid": { "normalized": "37425419" } }, "mesh": [], "publication": { "conference_name": null, "date": "2023 Jun 30", "date_precision": "day", "issue": "6", "normalized_date": "2023-06-30", "pages": "1245-1255", "proceedings_title": null, "publisher": "", "title": "Translational lung cancer research", "volume": "12", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Concordance between cryobiopsy and forceps biopsy specimens in assessment of immunohistochemistry staining for non-small cell lung carcinoma.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "We cloned and characterized two new coral fluorescent proteins: h2-3 and 1-41. h2-3 formed an obligate dimeric complex and exhibited bright green fluorescence. On the other hand, 1-41 formed a highly multimeric complex and exhibited dim red fluorescence. We engineered 1-41 into AzaleaB5, a practically useful red-emitting fluorescent protein for cellular labeling applications. We fused h2-3 and AzaleaB5 to the ubiquitination domains of human Geminin and Cdt1, respectively, to generate a new color variant of Fucci (Fluorescent Ubiquitination-based Cell-Cycle Indicator): Fucci5. We found Fucci5 provided more reliable nuclear labeling for monitoring cell-cycle progression than the 1(st) and 2(nd) generations that used mAG/mKO2 and mVenus/mCherry, respectively. Key Words: fluorescent protein, cell cycle, time-lapse imaging, flow cytometry.", "classifications": [ { "id": "JPMJCR2124", "label": "JPMJCR2124", "researcher": "Hirofumi Shintaku", "type": "grant" }, { "id": "Sawano", "label": "Group Sawano", "parent": "Shintaku", "type": "group" }, { "id": "Shintaku", "label": "Group Shintaku", "parent": "Shintaku", "type": "group" }, { "id": "Shintaku", "label": "Team Shintaku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Ryoko", "last_name": "Ando", "name": null }, { "creator_type": "author", "first_name": "Asako", "last_name": "Sakaue-Sawano", "name": null }, { "creator_type": "author", "first_name": "Keiko", "last_name": "Shoda", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Miyawaki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1247/csf.23028" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "37394513" } }, "mesh": [ { "descriptor": "Cell Cycle", "descriptor_ui": "D002453", "major_topic": false }, { "descriptor": "Cell Cycle Proteins", "descriptor_ui": "D018797", "major_topic": true }, { "descriptor": "Cell Division", "descriptor_ui": "D002455", "major_topic": false }, { "descriptor": "Color", "descriptor_ui": "D003116", "major_topic": false }, { "descriptor": "Coloring Agents", "descriptor_ui": "D004396", "major_topic": true }, { "descriptor": "Green Fluorescent Proteins", "descriptor_ui": "D049452", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Microscopy, Fluorescence", "descriptor_ui": "D008856", "major_topic": false } ], "publication": { "conference_name": null, "date": "2023 Jun 30", "date_precision": "day", "issue": "", "normalized_date": "2023-06-30", "pages": "", "proceedings_title": null, "publisher": "", "title": "Cell structure and function", "volume": "", "year": 2023 }, "ssbd": { "database": [ "ssbd-database-000316" ], "repository": [ "ssbd-repos-000316" ] }, "title": "Two coral fluorescent proteins of distinct colors for sharp visualization of cell-cycle progression.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Defects in gastric progenitor cell differentiation are associated with various gastric disorders, including atrophic gastritis, intestinal metaplasia, and gastric cancer. However, the mechanisms underlying the multilineage differentiation of gastric progenitor cells during healthy homeostasis remain poorly understood. Here, using a single-cell RNA sequencing method, Quartz-Seq2, we analyzed the gene expression dynamics of progenitor cell differentiation toward pit cell, neck cell, and parietal cell lineages in healthy adult mouse corpus tissues. Enrichment analysis of pseudotime-dependent genes and a gastric organoid assay revealed that EGFR-ERK signaling promotes pit cell differentiation, whereas NF-kappaB signaling maintains gastric progenitor cells in an undifferentiated state. In addition, pharmacological inhibition of EGFR in vivo resulted in a decreased number of pit cells. Although activation of EGFR signaling in gastric progenitor cells has been suggested as one of the major inducers of gastric cancers, our findings unexpectedly identified that EGFR signaling exerts a differentiation-promoting function, not a mitogenic function, in normal gastric homeostasis.", "classifications": [ { "id": "Nikaido", "label": "Group Nikaido", "parent": "Fujiwara", "type": "group" }, { "id": "Fujiwara", "label": "Team Fujiwara", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Hitomi", "last_name": "Takada", "name": null }, { "creator_type": "author", "first_name": "Yohei", "last_name": "Sasagawa", "name": null }, { "creator_type": "author", "first_name": "Mika", "last_name": "Yoshimura", "name": null }, { "creator_type": "author", "first_name": "Kaori", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Yoshimi", "last_name": "Iwayama", "name": null }, { "creator_type": "author", "first_name": "Tetsutaro", "last_name": "Hayashi", "name": null }, { "creator_type": "author", "first_name": "Ayako", "last_name": "Isomura-Matoba", "name": null }, { "creator_type": "author", "first_name": "Itoshi", "last_name": "Nikaido", "name": null }, { "creator_type": "author", "first_name": "Akira", "last_name": "Kurisaki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41467-023-39113-0" }, "pmcid": { "normalized": "PMC10310803" }, "pmid": { "normalized": "37386010" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "ErbB Receptors", "descriptor_ui": "D066246", "major_topic": false }, { "descriptor": "Homeostasis", "descriptor_ui": "D006706", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Stomach Neoplasms", "descriptor_ui": "D013274", "major_topic": true }, { "descriptor": "Transcriptome", "descriptor_ui": "D059467", "major_topic": true } ], "publication": { "conference_name": null, "date": "2023 Jun 29", "date_precision": "day", "issue": "1", "normalized_date": "2023-06-29", "pages": "3750", "proceedings_title": null, "publisher": "", "title": "Nature communications", "volume": "14", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Single-cell transcriptomics uncovers EGFR signaling-mediated gastric progenitor cell differentiation in stomach homeostasis.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "We have established a new transgenesis protocol based on CRISPR-Cas9, \"New and Easy XenopusTransgenesis (NEXTrans),\" and identified a novel safe harbor site in African clawed frogs, Xenopus laevis. We describe steps in detail for the construction of NEXTrans plasmid and guide RNA, CRISPR-Cas9-mediated NEXTrans plasmid integration into the locus, and its validation by genomic PCR. This improved strategy allows us to simply generate transgenic animals that stably express the transgene. For complete details on the use and execution of this protocol, please refer to Shibata et al. (2022).(1).", "classifications": [ { "id": "JPMJCR2025", "label": "JPMJCR2025", "researcher": "Yoshihiro Morishita", "type": "grant" }, { "id": "Morishita", "label": "Group Morishita", "parent": "Morishita", "type": "group" }, { "id": "Suzuki", "label": "Group Suzuki", "parent": "Morishita", "type": "group" }, { "id": "Morishita", "label": "Team Morishita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yuki", "last_name": "Shibata", "name": null }, { "creator_type": "author", "first_name": "Akinori", "last_name": "Okumura", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Mochii", "name": null }, { "creator_type": "author", "first_name": "Ken-Ichi T.", "last_name": "Suzuki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.xpro.2023.102382" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "37389994" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "CRISPR-Cas Systems", "descriptor_ui": "D064113", "major_topic": true }, { "descriptor": "Gene Transfer Techniques", "descriptor_ui": "D018014", "major_topic": false }, { "descriptor": "RNA, Guide, CRISPR-Cas Systems", "descriptor_ui": "D000094704", "major_topic": true }, { "descriptor": "Transgenes", "descriptor_ui": "D019076", "major_topic": false }, { "descriptor": "Xenopus laevis", "descriptor_ui": "D014982", "major_topic": false } ], "publication": { "conference_name": null, "date": "2023 Jun 28", "date_precision": "day", "issue": "3", "normalized_date": "2023-06-28", "pages": "102382", "proceedings_title": null, "publisher": "", "title": "STAR protocols", "volume": "4", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Protocols for transgenesis at a safe harbor site in the Xenopus laevis genome using CRISPR-Cas9.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: Ascidians significantly change their body structure through metamorphosis, but the spatio-temporal cell dynamics in the early metamorphosis stage has not been clarified. A natural Ciona embryo is surrounded by maternally derived non-self-test cells before metamorphosis. However, after metamorphosis, the juvenile is surrounded by self-tunic cells derived from mesenchymal cell lineages. Both test cells and tunic cells are thought to be changed their distributions during metamorphosis, but the precise timing is unknown. RESULTS: Using a metamorphosis induction by mechanical stimulation, we investigated the dynamics of mesenchymal cells during metamorphosis in a precise time course. After the stimulation, two-round Ca(2+) transients were observed. Migrating mesenchymal cells came out through the epidermis within 10 min after the second phase. We named this event \"cell extravasation.\" The cell extravasation occurred at the same time as the backward movement of posterior trunk epidermal cells. Timelapse imaging of transgenic-line larva revealed that non-self-test cells and self-tunic cells temporarily coexist outside the body until the test cells are eliminated. At the juvenile stage, only extravasated self-tunic cells remained outside the body. CONCLUSIONS: We found that mesenchymal cells extravasated following two-round Ca(2+) transients, and distributions of test cells and tunic cells changed in the outer body after tail regression.", "classifications": [ { "id": "Sawai", "label": "Group Sawai", "parent": "Sawai", "type": "group" }, { "id": "Sawai", "label": "Team Sawai", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Nozomu M.", "last_name": "Totsuka", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Kuwana", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Sawai", "name": null }, { "creator_type": "author", "first_name": "Kotaro", "last_name": "Oka", "name": null }, { "creator_type": "author", "first_name": "Yasunori", "last_name": "Sasakura", "name": null }, { "creator_type": "author", "first_name": "Kohji", "last_name": "Hotta", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/dvdy.636" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "37341471" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Ciona", "descriptor_ui": "D000077262", "major_topic": true }, { "descriptor": "Ciona intestinalis", "descriptor_ui": "D002938", "major_topic": true }, { "descriptor": "Epidermal Cells", "descriptor_ui": "D000078404", "major_topic": false }, { "descriptor": "Epidermis", "descriptor_ui": "D004817", "major_topic": false }, { "descriptor": "Larva", "descriptor_ui": "D007814", "major_topic": false }, { "descriptor": "Metamorphosis, Biological", "descriptor_ui": "D008675", "major_topic": false }, { "descriptor": "Urochordata", "descriptor_ui": "D014561", "major_topic": true } ], "publication": { "conference_name": null, "date": "2023 Jun 21", "date_precision": "day", "issue": "", "normalized_date": "2023-06-21", "pages": "", "proceedings_title": null, "publisher": "", "title": "Developmental dynamics : an official publication of the American Association of Anatomists", "volume": "", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Distribution changes of non-self-test cells and self-tunic cells surrounding the outer body during Ciona metamorphosis.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "We synthesized a (1-propylpyridinium)2[ReN(CN)4]-type organic-inorganic hybrid exhibiting water-vapor-induced drastic structural changes of the [ReN(CN)4]2- assemblies. Specifically, upon exposure to water vapor, dehydrated nitrido-bridged chains were converted to hydrated cyanido-bridged tetranuclear clusters via rearrangements of large molecular building units in the crystals. These switchable assembly forms display substantially different photo-physical properties, although in both cases the emission is caused by a metal-centered d-d transition. The nitrido-bridged chain exhibited a near-infrared (749 nm) emission, which blue-shifted as the temperature increased, while a visible (561 nm) emission and its red shift was demonstrated by the cyanido-bridged cluster.", "classifications": [ { "id": "Hijikata", "label": "Group Hijikata", "parent": "Tsuchiya", "type": "group" }, { "id": "Tsuchiya", "label": "Team Tsuchiya", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Ryo", "last_name": "Ohtani", "name": null }, { "creator_type": "author", "first_name": "Xu", "last_name": "Jianeng", "name": null }, { "creator_type": "author", "first_name": "Junichi", "last_name": "Yanagisawa", "name": null }, { "creator_type": "author", "first_name": "Yuudai", "last_name": "Iwai", "name": null }, { "creator_type": "author", "first_name": "Takumi", "last_name": "Ehara", "name": null }, { "creator_type": "author", "first_name": "Kiyoshi", "last_name": "Miyata", "name": null }, { "creator_type": "author", "first_name": "Ken", "last_name": "Onda", "name": null }, { "creator_type": "author", "first_name": "Jenny", "last_name": "Pirillo", "name": null }, { "creator_type": "author", "first_name": "Yuh", "last_name": "Hijikata", "name": null }, { "creator_type": "author", "first_name": "Tomoaki", "last_name": "Hiraoka", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Hayami", "name": null }, { "creator_type": "author", "first_name": "Benjamin", "last_name": "Le Ouay", "name": null }, { "creator_type": "author", "first_name": "Masaaki", "last_name": "Ohba", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/anie.202306853" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "37340936" } }, "mesh": [], "publication": { "conference_name": null, "date": "2023 Jun 21", "date_precision": "day", "issue": "", "normalized_date": "2023-06-21", "pages": "e202306853", "proceedings_title": null, "publisher": "", "title": "Angewandte Chemie (International ed. in English)", "volume": "", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Structural-transformation-induced Drastic Luminescence Changes in an Organic-Inorganic Hybrid [ReN(CN)4]2- Salt Triggered by Chemical Stimuli.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "In recent decades, human fathers across the globe have shown a substantial increase in their engagement in paternal caregiving behaviors. Despite the growing interest, the precise neurobiological mechanisms underlying caregiving behaviors in males remain unclear. Neurobiological studies conducted on rodents have advanced our understanding of the molecular, cellular, and circuit-level mechanisms. Typically, sexually naive males exhibit aggression toward offspring, while fathers display parental behaviors. This drastic behavioral plasticity may be associated with changes in connections among specific regions or cell types. Recent studies have begun to describe this structural plasticity by comparing neural connections before and after fatherhood. In this Perspective, we summarize the findings from four well-studied rodent species, namely prairie voles, California mice, laboratory rats, and laboratory mice, with a view toward integrating past and current progress. We then review recent advances in the understanding of structural plasticity for parental behaviors. Finally, we discuss remaining questions that require further exploration to gain a deeper understanding of the neural mechanisms underlying paternal behaviors in males, including their possible implications for the human brain.", "classifications": [ { "id": "Miyamichi", "label": "Group Miyamichi", "parent": "Enomoto", "type": "group" }, { "id": "Enomoto", "label": "Team Enomoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Kengo", "last_name": "Inada", "name": null }, { "creator_type": "author", "first_name": "Kazunari", "last_name": "Miyamichi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.neures.2023.06.007" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "37343600" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Arvicolinae", "descriptor_ui": "D003411", "major_topic": false }, { "descriptor": "Brain", "descriptor_ui": "D001921", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Parents", "descriptor_ui": "D010290", "major_topic": false }, { "descriptor": "Paternal Behavior", "descriptor_ui": "D010332", "major_topic": false }, { "descriptor": "Rodentia", "descriptor_ui": "D012377", "major_topic": true } ], "publication": { "conference_name": null, "date": "2023 Jun 19", "date_precision": "day", "issue": "", "normalized_date": "2023-06-19", "pages": "S0168-0102(23)00112-8", "proceedings_title": null, "publisher": "", "title": "Neuroscience research", "volume": "", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Association between parental behaviors and structural plasticity in the brain of male rodents.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: In the field of neuroscience, neural modules and circuits that control biological functions have been found throughout entire neural networks. Correlations in neural activity can be used to identify such neural modules. Recent technological advances enable us to measure whole-brain neural activity with single-cell resolution in several species including [Formula: see text]. Because current neural activity data in C. elegans contain many missing data points, it is necessary to merge results from as many animals as possible to obtain more reliable functional modules. RESULTS: In this work, we developed a new time-series clustering method, WormTensor, to identify functional modules using whole-brain activity data from C. elegans. WormTensor uses a distance measure, modified shape-based distance to account for the lags and the mutual inhibition of cell-cell interactions and applies the tensor decomposition algorithm multi-view clustering based on matrix integration using the higher orthogonal iteration of tensors (HOOI) algorithm (MC-MI-HOOI), which can estimate both the weight to account for the reliability of data from each animal and the clusters that are common across animals. CONCLUSION: We applied the method to 24 individual C. elegans and successfully found some known functional modules. Compared with a widely used consensus clustering method to aggregate multiple clustering results, WormTensor showed higher silhouette coefficients. Our simulation also showed that WormTensor is robust to contamination from noisy data. WormTensor is freely available as an R/CRAN package https://cran.r-project.org/web/packages/WormTensor .", "classifications": [ { "id": "Nikaido", "label": "Group Nikaido", "parent": "Fujiwara", "type": "group" }, { "id": "Fujiwara", "label": "Team Fujiwara", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Koki", "last_name": "Tsuyuzaki", "name": null }, { "creator_type": "author", "first_name": "Kentaro", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Yu", "last_name": "Toyoshima", "name": null }, { "creator_type": "author", "first_name": "Hirofumi", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Manami", "last_name": "Kanamori", "name": null }, { "creator_type": "author", "first_name": "Takayuki", "last_name": "Teramoto", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Ishihara", "name": null }, { "creator_type": "author", "first_name": "Yuichi", "last_name": "Iino", "name": null }, { "creator_type": "author", "first_name": "Itoshi", "last_name": "Nikaido", "name": null } ], "identifiers": { "doi": { "normalized": "10.1186/s12859-023-05230-2" }, "pmcid": { "normalized": "PMC10273573" }, "pmid": { "normalized": "37328814" } }, "mesh": [ { "descriptor": "Algorithms", "descriptor_ui": "D000465", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Brain", "descriptor_ui": "D001921", "major_topic": true }, { "descriptor": "Caenorhabditis elegans", "descriptor_ui": "D017173", "major_topic": true }, { "descriptor": "Cluster Analysis", "descriptor_ui": "D016000", "major_topic": false }, { "descriptor": "Reproducibility of Results", "descriptor_ui": "D015203", "major_topic": false } ], "publication": { "conference_name": null, "date": "2023 Jun 16", "date_precision": "day", "issue": "1", "normalized_date": "2023-06-16", "pages": "254", "proceedings_title": null, "publisher": "", "title": "BMC bioinformatics", "volume": "24", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "WormTensor: a clustering method for time-series whole-brain activity data from C. elegans.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "", "classifications": [ { "id": "Akaike", "label": "Group Akaike", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Shinichiro", "last_name": "Horii", "name": null }, { "creator_type": "author", "first_name": "Hirofumi", "last_name": "Sugawara", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Goto", "name": null }, { "creator_type": "author", "first_name": "Munetaka", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Tetsuro", "last_name": "Matsunaga", "name": null }, { "creator_type": "author", "first_name": "Daijirou", "last_name": "Akamatsu", "name": null }, { "creator_type": "author", "first_name": "Yuta", "last_name": "Tajima", "name": null }, { "creator_type": "author", "first_name": "Michihisa", "last_name": "Umetsu", "name": null }, { "creator_type": "author", "first_name": "Takaaki", "last_name": "Akaike", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Kamei", "name": null } ], "identifiers": { "doi": { "normalized": "10.1620/tjem.2023.j049" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "37316278" } }, "mesh": [ { "descriptor": "Atherosclerosis", "descriptor_ui": "D050197", "major_topic": true }, { "descriptor": "Helicobacter", "descriptor_ui": "D016998", "major_topic": true }, { "descriptor": "Helicobacter Infections", "descriptor_ui": "D016481", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false } ], "publication": { "conference_name": null, "date": "2023 Jun 15", "date_precision": "day", "issue": "", "normalized_date": "2023-06-15", "pages": "", "proceedings_title": null, "publisher": "", "title": "The Tohoku journal of experimental medicine", "volume": "", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Presence of Helicobacter cinaedi in Atherosclerotic Abdominal Aortic Aneurysmal Wall.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The activation and expansion of T cells that recognize cancer cells is an essential aspect to antitumor immunity. Tumors may escape destruction by the immune system through ectopic expression of inhibitory immune ligands typically exemplified by the PD-L1/PD-1 pathway. Here, we reveal another facet of tumor evasion from T cell surveillance. By secretome profiling of necrotic tumor cells, we identified an oncometabolite spermidine as a unique inhibitor of T cell receptor (TCR) signaling. Mechanistically, spermidine causes the downregulation of the plasma membrane cholesterol levels, resulting in the suppression of TCR clustering. Using syngeneic mouse models, we show that spermidine is abundantly detected in the tumor immune microenvironment (TIME) and that administration of the polyamine synthesis inhibitor effectively enhanced CD8+ T cell–dependent antitumor responses. Further, the combination of the polyamine synthesis inhibitor with anti-PD-1 immune checkpoint antibody resulted in a much stronger antitumor immune response. This study reveals an aspect of immunosuppressive TIME, wherein spermidine functions as a metabolic T cell checkpoint that may offer a unique approach for promoting tumor immunotherapy.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Sana", "last_name": "Hibino", "name": null }, { "creator_type": "author", "first_name": "Shotaro", "last_name": "Eto", "name": null }, { "creator_type": "author", "first_name": "Sho", "last_name": "Hangai", "name": null }, { "creator_type": "author", "first_name": "Keiko", "last_name": "Endo", "name": null }, { "creator_type": "author", "first_name": "Sanae", "last_name": "Ashitani", "name": null }, { "creator_type": "author", "first_name": "Maki", "last_name": "Sugaya", "name": null }, { "creator_type": "author", "first_name": "Tsuyoshi", "last_name": "Osawa", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Tadatsugu", "last_name": "Taniguchi", "name": null }, { "creator_type": "author", "first_name": "Hideyuki", "last_name": "Yanai", "name": null } ], "identifiers": { "doi": { "normalized": "10.1073/pnas.2305245120" }, "pmcid": { "normalized": null }, "pmid": { "normalized": null } }, "mesh": [], "publication": { "conference_name": null, "date": "2023-06-13", "date_precision": "day", "issue": "24", "normalized_date": "2023-06-13", "pages": "e2305245120", "proceedings_title": null, "publisher": "Proceedings of the National Academy of Sciences", "title": "Proceedings of the National Academy of Sciences", "volume": "120", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Tumor cell–derived spermidine is an oncometabolite that suppresses TCR clustering for intratumoral CD8+ T cell activation", "url": "https://www.pnas.org/doi/10.1073/pnas.2305245120", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Dormant seeds of a root parasitic plant Striga hermonthica sense strigolactones from host plants as environmental cues for germination. This process is mediated by diversified member of strigolactone receptors encoded by HYPOSENSITIVE TO LIGHT/KARRIKIN INSENSITIVE2 genes. It is known that warm and moist treatment of seed conditioning gradually turns dormant Striga seeds competent to respond strigolactones, while the mechanism behind it has been poorly understood. In this report, we show that plant hormone gibberellins increase the strigolactone-competence by up-regulating mRNA expressions of the major strigolactone receptors during the conditioning period. This idea was supported by poor germination phenotype when gibberellin biosynthesis is depleted by paclobutrazol during conditioning. Moreover, live-imaging with fluorogenic strigolactone-mimic, yoshimulactone green W, revealed that paclobutrazol treatment during conditioning caused aberrant dynamics of strigolactone perception after germination. These observations revealed an indirect role of gibberellins to the seed germination in Striga, which is contrastive to their roles as dominant germination stimulating hormone in non-parasitic plants. We propose a model of how the role of gibberellins become indirect during the evolution of parasitism in plants. Our work also highlight the potential role for gibberellins in field application, for instance, elevating the sensitivity of the seeds towards strigolactones in the current suicidal germination approach to alleviate the agricultural threats caused by this parasite in Africa.", "classifications": [ { "id": "JPMJCR1924", "label": "JPMJCR1924", "researcher": "Yuichiro Tsuchiya", "type": "grant" }, { "id": "Tsuchiya", "label": "Group Tsuchiya", "parent": "Tsuchiya", "type": "group" }, { "id": "Tsuchiya", "label": "Team Tsuchiya", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Jia Xin", "last_name": "Yap", "name": null }, { "creator_type": "author", "first_name": "Yuichiro", "last_name": "Tsuchiya", "name": null } ], "identifiers": { "doi": { "normalized": "10.1093/pcp/pcad056" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "37300550" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Germination", "descriptor_ui": "D018525", "major_topic": false }, { "descriptor": "Gibberellins", "descriptor_ui": "D005875", "major_topic": false }, { "descriptor": "Heterocyclic Compounds, 3-Ring", "descriptor_ui": "D006575", "major_topic": false }, { "descriptor": "Lactones", "descriptor_ui": "D007783", "major_topic": false }, { "descriptor": "Parasites", "descriptor_ui": "D010271", "major_topic": true }, { "descriptor": "Seeds", "descriptor_ui": "D012639", "major_topic": false }, { "descriptor": "Striga", "descriptor_ui": "D034362", "major_topic": true } ], "publication": { "conference_name": null, "date": "2023 Jun 10", "date_precision": "day", "issue": "", "normalized_date": "2023-06-10", "pages": "pcad056", "proceedings_title": null, "publisher": "", "title": "Plant & cell physiology", "volume": "", "year": 2023 }, "ssbd": { "database": [], "repository": [ "ssbd-repos-000301" ] }, "title": "Gibberellins promote seed conditioning by up-regulating strigolactone receptors in the parasitic plant Striga hermonthica.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Cystathionine gamma-lyase (CSE) is an enzyme responsible for the biosynthesis of cysteine from cystathionine in the final step of the transsulfuration pathway. It also has beta-lyase activity toward cystine, generating cysteine persulfide (Cys-SSH). The chemical reactivity of Cys-SSH is thought to be involved in the catalytic activity of particular proteins via protein polysulfidation, the formation of -S-(S)n-H on their reactive cysteine residues. The Cys136/171 residues of CSE have been proposed to be redox-sensitive residues. Herein, we investigated whether CSE polysulfidation occurs at Cys136/171 during cystine metabolism. Transfection of wild-type CSE into COS-7 cells resulted in increased intracellular Cys-SSH production, which was significantly increased when Cys136Val or Cys136/171Val CSE mutants were transfected, instead of the wild-type enzyme. A biotin-polyethylene glycol-conjugated maleimide capture assay revealed that CSE polysulfidation occurs at Cys136 during cystine metabolism. In vitro incubation of CSE with CSE-enzymatically synthesized Cys-SSH resulted in the inhibition of Cys-SSH production. In contrast, the mutant CSEs (Cys136Val and Cys136/171Val) proved resistant to inhibition. The Cys-SSH-producing CSE activity of Cys136/171Val CSE was higher than that of the wild-type enzyme. Meanwhile, the cysteine-producing CSE activity of this mutant was equivalent to that of the wild-type enzyme. It is assumed that Cys-SSH-producing CSE activity could be auto-inactivated via the polysulfidation of the enzyme during cystine metabolism. Thus, the polysulfidation of CSE at the Cys136 residue may be an integral feature of cystine metabolism, which functions to down-regulate Cys-SSH synthesis by the enzyme.", "classifications": [ { "id": "JPMJCR2024", "label": "JPMJCR2024", "researcher": "Motohiro Nishida", "type": "grant" } ], "creators": [ { "creator_type": "author", "first_name": "Shoma", "last_name": "Araki", "name": null }, { "creator_type": "author", "first_name": "Tsuyoshi", "last_name": "Takata", "name": null }, { "creator_type": "author", "first_name": "Katsuhiko", "last_name": "Ono", "name": null }, { "creator_type": "author", "first_name": "Tomohiro", "last_name": "Sawa", "name": null }, { "creator_type": "author", "first_name": "Shingo", "last_name": "Kasamatsu", "name": null }, { "creator_type": "author", "first_name": "Hideshi", "last_name": "Ihara", "name": null }, { "creator_type": "author", "first_name": "Yoshito", "last_name": "Kumagai", "name": null }, { "creator_type": "author", "first_name": "Takaaki", "last_name": "Akaike", "name": null }, { "creator_type": "author", "first_name": "Yasuo", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Yukihiro", "last_name": "Tsuchiya", "name": null } ], "identifiers": { "doi": { "normalized": "10.3390/ijms24129982" }, "pmcid": { "normalized": "PMC10298322" }, "pmid": { "normalized": "37373128" } }, "mesh": [ { "descriptor": "Cystathionine gamma-Lyase", "descriptor_ui": "D003542", "major_topic": true }, { "descriptor": "Cysteine", "descriptor_ui": "D003545", "major_topic": false }, { "descriptor": "Cystine", "descriptor_ui": "D003553", "major_topic": false }, { "descriptor": "Hydrogen Sulfide", "descriptor_ui": "D006862", "major_topic": true }, { "descriptor": "Oxidation-Reduction", "descriptor_ui": "D010084", "major_topic": false }, { "descriptor": "Proteins", "descriptor_ui": "D011506", "major_topic": false } ], "publication": { "conference_name": null, "date": "2023 Jun 10", "date_precision": "day", "issue": "12", "normalized_date": "2023-06-10", "pages": "", "proceedings_title": null, "publisher": "", "title": "International journal of molecular sciences", "volume": "24", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Cystathionine gamma-Lyase Self-Inactivates by Polysulfidation during Cystine Metabolism.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The development of novel antitumor agents and accompanying biomarkers has improved survival across several tumor types. Previously, we developed recommendations for tumor-agnostic treatments in patients with solid tumors with DNA mismatch repair deficient or neurotrophic receptor tyrosine kinase fusions. Recently, immune checkpoint inhibitors have shown efficacy in patient with tumor mutation burden-high (TMB-H) solid tumors and have been established as a third tumor-agnostic agent, making it necessary to develop the guideline prioritized for these patients. Clinical questions regarding medical care were formulated for patients with TMB-H advanced solid tumors. Relevant publications were searched by PubMed and Cochrane Database. Critical publications and conference reports were added manually. Systematic reviews were performed for each clinical question for the purpose of developing clinical recommendations. The committee members identified by Japan Society of Clinical Oncology (JSCO), Japanese Society of Medical Oncology (JSMO), and Japanese society of pediatric hematology/oncology (JSPHO) voted to determine the level of each recommendation considering the strength of evidence, expected risks and benefits to patients, and other related factors. Thereafter, a peer review by experts nominated from JSCO, JSMO, and JSPHO, and the public comments among all societies' members was done. The current guideline describes three clinical questions and seven recommendations for whom, when, and how TMB should be tested, and what is recommended for patients with TMB-H advanced solid tumors. In this guideline, the committee proposed seven recommendations for performing TMB testing properly to select patients who are likely to benefit from immunotherapy.", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Saori", "last_name": "Mishima", "name": null }, { "creator_type": "author", "first_name": "Yoichi", "last_name": "Naito", "name": null }, { "creator_type": "author", "first_name": "Kiwamu", "last_name": "Akagi", "name": null }, { "creator_type": "author", "first_name": "Naomi", "last_name": "Hayashi", "name": null }, { "creator_type": "author", "first_name": "Akira", "last_name": "Hirasawa", "name": null }, { "creator_type": "author", "first_name": "Tomoro", "last_name": "Hishiki", "name": null }, { "creator_type": "author", "first_name": "Ataru", "last_name": "Igarashi", "name": null }, { "creator_type": "author", "first_name": "Masafumi", "last_name": "Ikeda", "name": null }, { "creator_type": "author", "first_name": "Shigenori", "last_name": "Kadowaki", "name": null }, { "creator_type": "author", "first_name": "Hiroaki", "last_name": "Kajiyama", "name": null }, { "creator_type": "author", "first_name": "Motohiro", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Hirotsugu", "last_name": "Kenmotsu", "name": null }, { "creator_type": "author", "first_name": "Yasuhiro", "last_name": "Kodera", "name": null }, { "creator_type": "author", "first_name": "Keigo", "last_name": "Komine", "name": null }, { "creator_type": "author", "first_name": "Takafumi", "last_name": "Koyama", "name": null }, { "creator_type": "author", "first_name": "Osamu", "last_name": "Maeda", "name": null }, { "creator_type": "author", "first_name": "Mitsuru", "last_name": "Miyachi", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Nishihara", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Nishiyama", "name": null }, { "creator_type": "author", "first_name": "Shouichi", "last_name": "Ohga", "name": null }, { "creator_type": "author", "first_name": "Wataru", "last_name": "Okamoto", "name": null }, { "creator_type": "author", "first_name": "Eiji", "last_name": "Oki", "name": null }, { "creator_type": "author", "first_name": "Shigeru", "last_name": "Ono", "name": null }, { "creator_type": "author", "first_name": "Masashi", "last_name": "Sanada", "name": null }, { "creator_type": "author", "first_name": "Ikuo", "last_name": "Sekine", "name": null }, { "creator_type": "author", "first_name": "Tadao", "last_name": "Takano", "name": null }, { "creator_type": "author", "first_name": "Kayoko", "last_name": "Tao", "name": null }, { "creator_type": "author", "first_name": "Keita", "last_name": "Terashima", "name": null }, { "creator_type": "author", "first_name": "Katsuya", "last_name": "Tsuchihara", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null }, { "creator_type": "author", "first_name": "Takayuki", "last_name": "Yoshino", "name": null }, { "creator_type": "author", "first_name": "Eishi", "last_name": "Baba", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/s10147-023-02360-8" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "37300720" } }, "mesh": [ { "descriptor": "B7-H1 Antigen", "descriptor_ui": "D060890", "major_topic": false }, { "descriptor": "Biomarkers, Tumor", "descriptor_ui": "D014408", "major_topic": false }, { "descriptor": "Brain Neoplasms", "descriptor_ui": "D001932", "major_topic": true }, { "descriptor": "Child", "descriptor_ui": "D002648", "major_topic": false }, { "descriptor": "East Asian People", "descriptor_ui": "D000095225", "major_topic": false }, { "descriptor": "Hematology", "descriptor_ui": "D006405", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Immunotherapy", "descriptor_ui": "D007167", "major_topic": false }, { "descriptor": "Japan", "descriptor_ui": "D007564", "major_topic": false }, { "descriptor": "Medical Oncology", "descriptor_ui": "D008495", "major_topic": false }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": false } ], "publication": { "conference_name": null, "date": "2023 Jun 10", "date_precision": "day", "issue": "", "normalized_date": "2023-06-10", "pages": "", "proceedings_title": null, "publisher": "", "title": "International journal of clinical oncology", "volume": "", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Japanese Society of Medical Oncology/Japan Society of Clinical Oncology/Japanese Society of Pediatric Hematology/Oncology-led clinical recommendations on the diagnosis and use of immunotherapy in patients with high tumor mutational burden tumors.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "To promote the clinical application of human induced pluripotent stem cell (hiPSC)-derived hepatocytes, a method capable of monitoring regenerative processes and assessing differentiation efficiency without harming or modifying these cells is important. Raman microscopy provides a powerful tool for this as it enables label-free identification of intracellular biomolecules in live samples. Here, we used label-free Raman microscopy to assess hiPSC differentiation into hepatocyte lineage based on the intracellular chemical content. We contrasted these data with similar phenotypes from the HepaRG and from commercially available hiPSC-derived hepatocytes (iCell hepatocytes). We detected hepatic cytochromes, lipids, and glycogen in hiPSC-derived hepatocyte-like cells (HLCs) but not biliary-like cells (BLCs), indicating intrinsic differences in biomolecular content between these phenotypes. The data show significant glycogen and lipid accumulation as early as the definitive endoderm transition. Additionally, we explored the use of Raman imaging as a hepatotoxicity assay for the HepaRG and iCell hepatocytes, with data displaying a dose-dependent reduction of glycogen accumulation in response to acetaminophen. These findings show that the nondestructive and high-content nature of Raman imaging provides a promising tool for both quality control of hiPSC-derived hepatocytes and hepatotoxicity screening.", "classifications": [ { "id": "Fujita", "label": "Group Fujita", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Menglu", "last_name": "Li", "name": null }, { "creator_type": "author", "first_name": "Yukiko", "last_name": "Ueyama-Toba", "name": null }, { "creator_type": "author", "first_name": "Matthew", "last_name": "Lindley", "name": null }, { "creator_type": "author", "first_name": "Gunganist", "last_name": "Kongklad", "name": null }, { "creator_type": "author", "first_name": "Yasunori", "last_name": "Nawa", "name": null }, { "creator_type": "author", "first_name": "Yasuaki", "last_name": "Kumamoto", "name": null }, { "creator_type": "author", "first_name": "Seiichi", "last_name": "Ishida", "name": null }, { "creator_type": "author", "first_name": "Yasunari", "last_name": "Kanda", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Fujita", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Mizuguchi", "name": null }, { "creator_type": "author", "first_name": "Katsumasa", "last_name": "Fujita", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/acs.analchem.3c00976" }, "pmcid": { "normalized": null }, "pmid": { "normalized": null } }, "mesh": [], "publication": { "conference_name": null, "date": "2023-06-09", "date_precision": "day", "issue": "", "normalized_date": "2023-06-09", "pages": "", "proceedings_title": null, "publisher": "American Chemical Society", "title": "Analytical Chemistry", "volume": "", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Label-Free Evaluation of Maturation and Hepatotoxicity of Human iPSC-Derived Hepatocytes Using Hyperspectral Raman Imaging", "url": "https://doi.org/10.1021/acs.analchem.3c00976", "zotero": { "item_type": "journalArticle" } }, { "abstract": "SIGNIFICANCE: Routine exposure to xenobiotics is unavoidable during our lifetimes. Certain xenobiotics are hazardous to human health, and are metabolized in the body to render them less toxic. During this process, several detoxification enzymes cooperatively metabolize xenobiotics. Glutathione (GSH) conjugation plays an important role in the metabolism of electrophilic xenobiotics. RECENT ADVANCES: Recent advances in reactive sulfur and supersulfide (RSS) analyses showed that persulfides and polysulfides bound to low-molecular-weight thiols, such as GSH and to protein thiols are abundant in both eukaryotes and prokaryotes. The highly nucleophilic nature of hydropersulfides and hydropolysulfides contributes to cell protection against oxidative stress and electrophilic stress. CRITICAL ISSUES: In contrast to GSH conjugation to electrophiles that is aided by glutathione S-transferase (GST), persulfides and polysulfides can directly form conjugates with electrophiles without the catalytic actions of GST. The polysulfur bonds in the conjugates are further reduced by perthioanions and polythioanions derived from RSS to form sulfhydrated metabolites that are no longer electrophilic but rather nucleophilic and differ from metabolites that are formed via GSH conjugation. FUTURE DIRECTIONS: In view of the abundance of RSS in cells and tissues, metabolism of xenobiotics that is mediated by RSS warrants additional investigations, such as studies of the impact of microbiota-derived RSS on xenobiotic metabolism. Metabolites formed from reactions between electrophiles and RSS may be potential biomarkers for monitoring exposure to electrophiles and for studying their metabolism by RSS.", "classifications": [ { "id": "Akaike", "label": "Group Akaike", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Tianli", "last_name": "Zhang", "name": null }, { "creator_type": "author", "first_name": "Takaaki", "last_name": "Akaike", "name": null }, { "creator_type": "author", "first_name": "Tomohiro", "last_name": "Sawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1089/ars.2022.0172" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "37294201" } }, "mesh": [ { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Oxidation-Reduction", "descriptor_ui": "D010084", "major_topic": false }, { "descriptor": "Sulfhydryl Compounds", "descriptor_ui": "D013438", "major_topic": false }, { "descriptor": "Sulfides", "descriptor_ui": "D013440", "major_topic": true }, { "descriptor": "Sulfur", "descriptor_ui": "D013455", "major_topic": true }, { "descriptor": "Xenobiotics", "descriptor_ui": "D015262", "major_topic": true } ], "publication": { "conference_name": null, "date": "2023 Jun 9", "date_precision": "day", "issue": "", "normalized_date": "2023-06-09", "pages": "", "proceedings_title": null, "publisher": "", "title": "Antioxidants & redox signaling", "volume": "", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Redox Regulation of Xenobiotics by Reactive Sulfur and Supersulfide Species.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Kinetochore is an essential protein complex required for accurate chromosome segregation. The constitutive centromere-associated network (CCAN), a subcomplex of the kinetochore, associates with centromeric chromatin and provides a platform for the kinetochore assembly. The CCAN protein CENP-C is thought to be a central hub for the centromere/kinetochore organization. However, the role of CENP-C in CCAN assembly needs to be elucidated. Here, we demonstrate that both the CCAN-binding domain and the C-terminal region that includes the Cupin domain of CENP-C are necessary and sufficient for chicken CENP-C function. Structural and biochemical analyses reveal self-oligomerization of the Cupin domains of chicken and human CENP-C. We find that the CENP-C Cupin domain oligomerization is vital for CENP-C function, centromeric localization of CCAN, and centromeric chromatin organization. These results suggest that CENP-C facilitates the centromere/kinetochore assembly through its oligomerization.", "classifications": [ { "id": "Onami", "label": "Group Onami", "parent": "Fujiwara", "type": "group" }, { "id": "Fujiwara", "label": "Team Fujiwara", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Masatoshi", "last_name": "Hara", "name": null }, { "creator_type": "author", "first_name": "Mariko", "last_name": "Ariyoshi", "name": null }, { "creator_type": "author", "first_name": "Tomoki", "last_name": "Sano", "name": null }, { "creator_type": "author", "first_name": "Ryu-Suke", "last_name": "Nozawa", "name": null }, { "creator_type": "author", "first_name": "Soya", "last_name": "Shinkai", "name": null }, { "creator_type": "author", "first_name": "Shuichi", "last_name": "Onami", "name": null }, { "creator_type": "author", "first_name": "Isabelle", "last_name": "Jansen", "name": null }, { "creator_type": "author", "first_name": "Toru", "last_name": "Hirota", "name": null }, { "creator_type": "author", "first_name": "Tatsuo", "last_name": "Fukagawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.molcel.2023.05.023" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "37295434" } }, "mesh": [ { "descriptor": "Centromere", "descriptor_ui": "D002503", "major_topic": true }, { "descriptor": "Centromere Protein A", "descriptor_ui": "D000076247", "major_topic": false }, { "descriptor": "Chromatin", "descriptor_ui": "D002843", "major_topic": false }, { "descriptor": "Chromosomal Proteins, Non-Histone", "descriptor_ui": "D002868", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Kinetochores", "descriptor_ui": "D018386", "major_topic": true } ], "publication": { "conference_name": null, "date": "2023 Jun 6", "date_precision": "day", "issue": "", "normalized_date": "2023-06-06", "pages": "S1097-2765(23)00379-9", "proceedings_title": null, "publisher": "", "title": "Molecular cell", "volume": "", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Centromere/kinetochore is assembled through CENP-C oligomerization.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Maintenance of metabolic homeostasis is secured by metabolite-sensing systems, which can be overwhelmed by constant macronutrient surplus in obesity. Not only the uptake processes but also the consumption of energy substrates determine the cellular metabolic burden. We herein describe a novel transcriptional system in this context comprised of peroxisome proliferator-activated receptor alpha (PPARalpha), a master regulator for fatty acid oxidation, and C-terminal binding protein 2 (CtBP2), a metabolite-sensing transcriptional co-repressor. CtBP2 interacts with PPARalpha to repress its activity, and the interaction is enhanced upon binding to malonyl-CoA, a metabolic intermediate increased in tissues in obesity and reported to suppress fatty acid oxidation through inhibition of carnitine palmitoyltransferase 1 (CPT1). In line with our preceding observations that CtBP2 adopts a monomeric configuration upon binding to acyl-CoAs, we determined that mutations in CtBP2 that shift the conformational equilibrium toward monomers increase the interaction between CtBP2 and PPARalpha. In contrast, metabolic manipulations that reduce malonyl-CoA decreased the formation of the CtBP2/PPARalpha complex. Consistent with these in vitro findings, we found that the CtBP2/PPARalpha interaction is accelerated in obese livers while genetic deletion of CtBP2 in the liver causes derepression of PPARalpha target genes. These findings support our model where CtBP2 exists primarily as a monomer in the metabolic milieu of obesity to repress PPARalpha, representing a liability in metabolic diseases that can be exploited to develop therapeutic approaches.", "classifications": [ { "id": "Miyamoto", "label": "Group Miyamoto", "parent": "Wakamoto", "type": "group" }, { "id": "Wakamoto", "label": "Team Wakamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Kenji", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Motohiro", "last_name": "Sekiya", "name": null }, { "creator_type": "author", "first_name": "Kenta", "last_name": "Kainoh", "name": null }, { "creator_type": "author", "first_name": "Ryunosuke", "last_name": "Yoshino", "name": null }, { "creator_type": "author", "first_name": "Akio", "last_name": "Hayashi", "name": null }, { "creator_type": "author", "first_name": "Song-Iee", "last_name": "Han", "name": null }, { "creator_type": "author", "first_name": "Masaya", "last_name": "Araki", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Ohno", "name": null }, { "creator_type": "author", "first_name": "Yoshinori", "last_name": "Takeuchi", "name": null }, { "creator_type": "author", "first_name": "Tomomi", "last_name": "Tsuyuzaki", "name": null }, { "creator_type": "author", "first_name": "Daichi", "last_name": "Yamazaki", "name": null }, { "creator_type": "author", "first_name": "Chen", "last_name": "Wanpei", "name": null }, { "creator_type": "author", "first_name": "Lisa", "last_name": "Hada", "name": null }, { "creator_type": "author", "first_name": "Sho", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Putu Indah", "last_name": "Paramita Adi Putri", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Murayama", "name": null }, { "creator_type": "author", "first_name": "Yoko", "last_name": "Sugano", "name": null }, { "creator_type": "author", "first_name": "Yoshinori", "last_name": "Osaki", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Iwasaki", "name": null }, { "creator_type": "author", "first_name": "Naoya", "last_name": "Yahagi", "name": null }, { "creator_type": "author", "first_name": "Hiroaki", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Takafumi", "last_name": "Miyamoto", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Matsuzaka", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Shimano", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.jbc.2023.104890" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "37286039" } }, "mesh": [ { "descriptor": "Alcohol Oxidoreductases", "descriptor_ui": "D000429", "major_topic": true }, { "descriptor": "Allosteric Regulation", "descriptor_ui": "D000494", "major_topic": false }, { "descriptor": "Co-Repressor Proteins", "descriptor_ui": "D056970", "major_topic": true }, { "descriptor": "Fatty Acids", "descriptor_ui": "D005227", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Liver", "descriptor_ui": "D008099", "major_topic": false }, { "descriptor": "Obesity", "descriptor_ui": "D009765", "major_topic": true }, { "descriptor": "PPAR alpha", "descriptor_ui": "D047493", "major_topic": true } ], "publication": { "conference_name": null, "date": "2023 Jun 5", "date_precision": "day", "issue": "", "normalized_date": "2023-06-05", "pages": "104890", "proceedings_title": null, "publisher": "", "title": "The Journal of biological chemistry", "volume": "", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Obesity-induced metabolic imbalance allosterically modulates CtBP2 to inhibit PPAR-alpha transcriptional activity.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Plants use many long-distance and systemic signals to modulate growth and development, as well as respond to biotic and abiotic stresses. Parasitic nematodes infect host plant roots and cause severe damage to crop plants. However, the molecular mechanisms that regulate parasitic nematode infections are still unknown. Here, we show that plant parasitic root-knot nematodes (RKNs), Meloidogyne incognita, modulate the host CLAVATA3 (CLV3)/EMBRYO SURROUNDING REGION (CLE)-CLV1 signaling module to promote the infection progression. Plants deficient in the CLE signaling pathway show enhanced RKN resistance, whereas CLE overexpression leads to increased susceptibility toward RKN. Grafting analysis shows that CLV1 expression in the shoot alone is sufficient to positively regulate RKN infection. Together with results from the split-root culture system, infection assays, and CLE3-CLV1 binding assays, we conclude that mobile root-derived CLE signals are perceived by CLV1 in the shoot, which subsequently produce systemic signals to promote gall formation and RKN reproduction.", "classifications": [ { "id": "Sato", "label": "Group Sato", "parent": "Tsuchiya", "type": "group" }, { "id": "Tsuchiya", "label": "Team Tsuchiya", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Satoru", "last_name": "Nakagami", "name": null }, { "creator_type": "author", "first_name": "Michitaka", "last_name": "Notaguchi", "name": null }, { "creator_type": "author", "first_name": "Tatsuhiko", "last_name": "Kondo", "name": null }, { "creator_type": "author", "first_name": "Satoru", "last_name": "Okamoto", "name": null }, { "creator_type": "author", "first_name": "Takanori", "last_name": "Ida", "name": null }, { "creator_type": "author", "first_name": "Yoshikatsu", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Tetsuya", "last_name": "Higashiyama", "name": null }, { "creator_type": "author", "first_name": "Allen Yi-Lun", "last_name": "Tsai", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Ishida", "name": null }, { "creator_type": "author", "first_name": "Shinichiro", "last_name": "Sawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1126/sciadv.adf4803" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "37267361" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Plants", "descriptor_ui": "D010944", "major_topic": true }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Tylenchoidea", "descriptor_ui": "D014431", "major_topic": true } ], "publication": { "conference_name": null, "date": "2023 Jun 2", "date_precision": "day", "issue": "22", "normalized_date": "2023-06-02", "pages": "eadf4803", "proceedings_title": null, "publisher": "", "title": "Science advances", "volume": "9", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Root-knot nematode modulates plant CLE3-CLV1 signaling as a long-distance signal for successful infection.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "In developing brains, activity-dependent remodeling facilitates the formation of precise neuronal connectivity. Synaptic competition is known to facilitate synapse elimination; however, it has remained unknown how different synapses compete with one another within a post-synaptic cell. Here, we investigate how a mitral cell in the mouse olfactory bulb prunes all but one primary dendrite during the developmental remodeling process. We find that spontaneous activity generated within the olfactory bulb is essential. We show that strong glutamatergic inputs to one dendrite trigger branch-specific changes in RhoA activity to facilitate the pruning of the remaining dendrites: NMDAR-dependent local signals suppress RhoA to protect it from pruning; however, the subsequent neuronal depolarization induces neuron-wide activation of RhoA to prune non-protected dendrites. NMDAR-RhoA signals are also essential for the synaptic competition in the mouse barrel cortex. Our results demonstrate a general principle whereby activity-dependent lateral inhibition across synapses establishes a discrete receptive field of a neuron.", "classifications": [ { "id": "JPMJCR2021", "label": "JPMJCR2021", "researcher": "Hideki Enomoto", "type": "grant" }, { "id": "Enomoto", "label": "Group Enomoto", "parent": "Enomoto", "type": "group" }, { "id": "Imai", "label": "Group Imai", "parent": "Enomoto", "type": "group" }, { "id": "Enomoto", "label": "Team Enomoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Satoshi", "last_name": "Fujimoto", "name": null }, { "creator_type": "author", "first_name": "Marcus N.", "last_name": "Leiwe", "name": null }, { "creator_type": "author", "first_name": "Shuhei", "last_name": "Aihara", "name": null }, { "creator_type": "author", "first_name": "Richi", "last_name": "Sakaguchi", "name": null }, { "creator_type": "author", "first_name": "Yuko", "last_name": "Muroyama", "name": null }, { "creator_type": "author", "first_name": "Reiko", "last_name": "Kobayakawa", "name": null }, { "creator_type": "author", "first_name": "Ko", "last_name": "Kobayakawa", "name": null }, { "creator_type": "author", "first_name": "Tetsuichiro", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Imai", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.devcel.2023.05.004" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "37290446" } }, "mesh": [ { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Dendrites", "descriptor_ui": "D003712", "major_topic": true }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Olfactory Bulb", "descriptor_ui": "D009830", "major_topic": true }, { "descriptor": "Synapses", "descriptor_ui": "D013569", "major_topic": false } ], "publication": { "conference_name": null, "date": "2023 May 30", "date_precision": "day", "issue": "", "normalized_date": "2023-05-30", "pages": "S1534-5807(23)00237-X", "proceedings_title": null, "publisher": "", "title": "Developmental cell", "volume": "", "year": 2023 }, "ssbd": { "database": [ "ssbd-database-000289" ], "repository": [ "ssbd-repos-000289" ] }, "title": "Activity-dependent local protection and lateral inhibition control synaptic competition in developing mitral cells in mice.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Formation of oriented myofibrils is a key event in musculoskeletal development. However, the mechanisms that drive myocyte orientation and fusion to control muscle directionality in adults remain enigmatic. Here, we demonstrate that the developing skeleton instructs the directional outgrowth of skeletal muscle and other soft tissues during limb and facial morphogenesis in zebrafish and mouse. Time-lapse live imaging reveals that during early craniofacial development, myoblasts condense into round clusters corresponding to future muscle groups. These clusters undergo oriented stretch and alignment during embryonic growth. Genetic perturbation of cartilage patterning or size disrupts the directionality and number of myofibrils in vivo. Laser ablation of musculoskeletal attachment points reveals tension imposed by cartilage expansion on the forming myofibers. Application of continuous tension using artificial attachment points, or stretchable membrane substrates, is sufficient to drive polarization of myocyte populations in vitro. Overall, this work outlines a biomechanical guidance mechanism that is potentially useful for engineering functional skeletal muscle.", "classifications": [ { "id": "Maki", "label": "Group Maki", "parent": "Toyoshima", "type": "group" }, { "id": "Yamamoto", "label": "Group Yamamoto", "parent": "Toyoshima", "type": "group" }, { "id": "Toyoshima", "label": "Team Toyoshima", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Kazunori", "last_name": "Sunadome", "name": null }, { "creator_type": "author", "first_name": "Alek G.", "last_name": "Erickson", "name": null }, { "creator_type": "author", "first_name": "Delf", "last_name": "Kah", "name": null }, { "creator_type": "author", "first_name": "Ben", "last_name": "Fabry", "name": null }, { "creator_type": "author", "first_name": "Csaba", "last_name": "Adori", "name": null }, { "creator_type": "author", "first_name": "Polina", "last_name": "Kameneva", "name": null }, { "creator_type": "author", "first_name": "Louis", "last_name": "Faure", "name": null }, { "creator_type": "author", "first_name": "Shigeaki", "last_name": "Kanatani", "name": null }, { "creator_type": "author", "first_name": "Marketa", "last_name": "Kaucka", "name": null }, { "creator_type": "author", "first_name": "Ivar", "last_name": "Dehnisch Ellstrom", "name": null }, { "creator_type": "author", "first_name": "Marketa", "last_name": "Tesarova", "name": null }, { "creator_type": "author", "first_name": "Tomas", "last_name": "Zikmund", "name": null }, { "creator_type": "author", "first_name": "Jozef", "last_name": "Kaiser", "name": null }, { "creator_type": "author", "first_name": "Steven", "last_name": "Edwards", "name": null }, { "creator_type": "author", "first_name": "Koichiro", "last_name": "Maki", "name": null }, { "creator_type": "author", "first_name": "Taiji", "last_name": "Adachi", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Kaj", "last_name": "Fried", "name": null }, { "creator_type": "author", "first_name": "Igor", "last_name": "Adameyko", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41467-023-38647-7" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "37244931" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Morphogenesis", "descriptor_ui": "D009024", "major_topic": false }, { "descriptor": "Muscle, Skeletal", "descriptor_ui": "D018482", "major_topic": true }, { "descriptor": "Myoblasts", "descriptor_ui": "D032446", "major_topic": false }, { "descriptor": "Myofibrils", "descriptor_ui": "D009210", "major_topic": false }, { "descriptor": "Zebrafish", "descriptor_ui": "D015027", "major_topic": true } ], "publication": { "conference_name": null, "date": "2023 May 27", "date_precision": "day", "issue": "1", "normalized_date": "2023-05-27", "pages": "3060", "proceedings_title": null, "publisher": "", "title": "Nature communications", "volume": "14", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Directionality of developing skeletal muscles is set by mechanical forces.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Lung adenocarcinoma is the most common type of lung cancer. Known risk variants explain only a small fraction of lung adenocarcinoma heritability. Here, we conducted a two-stage genome-wide association study of lung adenocarcinoma of East Asian ancestry (21,658 cases and 150,676 controls; 54.5% never-smokers) and identified 12 novel susceptibility variants, bringing the total number to 28 at 25 independent loci. Transcriptome-wide association analyses together with colocalization studies using a Taiwanese lung expression quantitative trait loci dataset (n = 115) identified novel candidate genes, including FADS1 at 11q12 and ELF5 at 11p13. In a multi-ancestry meta-analysis of East Asian and European studies, four loci were identified at 2p11, 4q32, 16q23, and 18q12. At the same time, most of our findings in East Asian populations showed no evidence of association in European populations. In our studies drawn from East Asian populations, a polygenic risk score based on the 25 loci had a stronger association in never-smokers vs. individuals with a history of smoking (P(interaction) = 0.0058). These findings provide new insights into the etiology of lung adenocarcinoma in individuals from East Asian populations, which could be important in developing translational applications.", "classifications": [ { "id": "Hamamoto", "label": "Group Hamamoto", "parent": "Okamoto", "type": "group" }, { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Jianxin", "last_name": "Shi", "name": null }, { "creator_type": "author", "first_name": "Kouya", "last_name": "Shiraishi", "name": null }, { "creator_type": "author", "first_name": "Jiyeon", "last_name": "Choi", "name": null }, { "creator_type": "author", "first_name": "Keitaro", "last_name": "Matsuo", "name": null }, { "creator_type": "author", "first_name": "Tzu-Yu", "last_name": "Chen", "name": null }, { "creator_type": "author", "first_name": "Juncheng", "last_name": "Dai", "name": null }, { "creator_type": "author", "first_name": "Rayjean J.", "last_name": "Hung", "name": null }, { "creator_type": "author", "first_name": "Kexin", "last_name": "Chen", "name": null }, { "creator_type": "author", "first_name": "Xiao-Ou", "last_name": "Shu", "name": null }, { "creator_type": "author", "first_name": "Young Tae", "last_name": "Kim", "name": null }, { "creator_type": "author", "first_name": "Maria Teresa", "last_name": "Landi", "name": null }, { "creator_type": "author", "first_name": "Dongxin", "last_name": "Lin", "name": null }, { "creator_type": "author", "first_name": "Wei", "last_name": "Zheng", "name": null }, { "creator_type": "author", "first_name": "Zhihua", "last_name": "Yin", "name": null }, { "creator_type": "author", "first_name": "Baosen", "last_name": "Zhou", "name": null }, { "creator_type": "author", "first_name": "Bao", "last_name": "Song", "name": null }, { "creator_type": "author", "first_name": "Jiucun", "last_name": "Wang", "name": null }, { "creator_type": "author", "first_name": "Wei Jie", "last_name": "Seow", "name": null }, { "creator_type": "author", "first_name": "Lei", "last_name": "Song", "name": null }, { "creator_type": "author", "first_name": "I.-Shou", "last_name": "Chang", "name": null }, { "creator_type": "author", "first_name": "Wei", "last_name": "Hu", "name": null }, { "creator_type": "author", "first_name": "Li-Hsin", "last_name": "Chien", "name": null }, { "creator_type": "author", "first_name": "Qiuyin", "last_name": "Cai", "name": null }, { "creator_type": "author", "first_name": "Yun-Chul", "last_name": "Hong", "name": null }, { "creator_type": "author", "first_name": "Hee Nam", "last_name": "Kim", "name": null }, { "creator_type": "author", "first_name": "Yi-Long", "last_name": "Wu", "name": null }, { "creator_type": "author", "first_name": "Maria Pik", "last_name": "Wong", "name": null }, { "creator_type": "author", "first_name": "Brian Douglas", "last_name": "Richardson", "name": null }, { "creator_type": "author", "first_name": "Karen M.", "last_name": "Funderburk", "name": null }, { "creator_type": "author", "first_name": "Shilan", "last_name": "Li", "name": null }, { "creator_type": "author", "first_name": "Tongwu", "last_name": "Zhang", "name": null }, { "creator_type": "author", "first_name": "Charles", "last_name": "Breeze", "name": null }, { "creator_type": "author", "first_name": "Zhaoming", "last_name": "Wang", "name": null }, { "creator_type": "author", "first_name": "Batel", "last_name": "Blechter", "name": null }, { "creator_type": "author", "first_name": "Bryan A.", "last_name": "Bassig", "name": null }, { "creator_type": "author", "first_name": "Jin Hee", "last_name": "Kim", "name": null }, { "creator_type": "author", "first_name": "Demetrius", "last_name": "Albanes", "name": null }, { "creator_type": "author", "first_name": "Jason Y. 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H.", "last_name": "Vermeulen", "name": null }, { "creator_type": "author", "first_name": "Iona", "last_name": "Cheng", "name": null }, { "creator_type": "author", "first_name": "Junjie", "last_name": "Wu", "name": null }, { "creator_type": "author", "first_name": "Wei-Yen", "last_name": "Lim", "name": null }, { "creator_type": "author", "first_name": "Fang-Yu", "last_name": "Tsai", "name": null }, { "creator_type": "author", "first_name": "John K. C.", "last_name": "Chan", "name": null }, { "creator_type": "author", "first_name": "Jihua", "last_name": "Li", "name": null }, { "creator_type": "author", "first_name": "Hongyan", "last_name": "Chen", "name": null }, { "creator_type": "author", "first_name": "Hsien-Chih", "last_name": "Lin", "name": null }, { "creator_type": "author", "first_name": "Li", "last_name": "Jin", "name": null }, { "creator_type": "author", "first_name": "Jie", "last_name": "Liu", "name": null }, { "creator_type": "author", "first_name": "Norie", "last_name": "Sawada", "name": null }, { "creator_type": "author", "first_name": "Taiki", "last_name": "Yamaji", "name": null }, { "creator_type": "author", "first_name": "Kathleen", "last_name": "Wyatt", "name": null }, { "creator_type": "author", "first_name": "Shengchao A.", "last_name": "Li", "name": null }, { "creator_type": "author", "first_name": "Hongxia", "last_name": "Ma", "name": null }, { "creator_type": "author", "first_name": "Meng", "last_name": "Zhu", "name": null }, { "creator_type": "author", "first_name": "Zhehai", "last_name": "Wang", "name": null }, { "creator_type": "author", "first_name": "Sensen", "last_name": "Cheng", "name": null }, { "creator_type": "author", "first_name": "Xuelian", "last_name": "Li", "name": null }, { "creator_type": "author", "first_name": "Yangwu", "last_name": "Ren", "name": null }, { "creator_type": "author", "first_name": "Ann", "last_name": "Chao", "name": null }, { "creator_type": "author", "first_name": "Motoki", "last_name": "Iwasaki", "name": null }, { "creator_type": "author", "first_name": "Junjie", "last_name": "Zhu", "name": null }, { "creator_type": "author", "first_name": "Gening", "last_name": "Jiang", "name": null }, { "creator_type": "author", "first_name": "Ke", "last_name": "Fei", "name": null }, { "creator_type": "author", "first_name": "Guoping", "last_name": "Wu", "name": null }, { "creator_type": "author", "first_name": "Chih-Yi", "last_name": "Chen", "name": null }, { "creator_type": "author", "first_name": "Chien-Jen", "last_name": "Chen", "name": null }, { "creator_type": "author", "first_name": "Pan-Chyr", "last_name": "Yang", "name": null }, { "creator_type": "author", "first_name": "Jinming", "last_name": "Yu", "name": null }, { "creator_type": "author", "first_name": "Victoria L.", "last_name": "Stevens", "name": null }, { "creator_type": "author", "first_name": "Joseph F. Jr", "last_name": "Fraumeni", "name": null }, { "creator_type": "author", "first_name": "Nilanjan", "last_name": "Chatterjee", "name": null }, { "creator_type": "author", "first_name": "Olga Y.", "last_name": "Gorlova", "name": null }, { "creator_type": "author", "first_name": "Chao Agnes", "last_name": "Hsiung", "name": null }, { "creator_type": "author", "first_name": "Christopher I.", "last_name": "Amos", "name": null }, { "creator_type": "author", "first_name": "Hongbing", "last_name": "Shen", "name": null }, { "creator_type": "author", "first_name": "Stephen J.", "last_name": "Chanock", "name": null }, { "creator_type": "author", "first_name": "Nathaniel", "last_name": "Rothman", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Kohno", "name": null }, { "creator_type": "author", "first_name": "Qing", "last_name": "Lan", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41467-023-38196-z" }, "pmcid": { "normalized": "PMC10220065" }, "pmid": { "normalized": "37236969" } }, "mesh": [ { "descriptor": "Adenocarcinoma of Lung", "descriptor_ui": "D000077192", "major_topic": true }, { "descriptor": "Asia, Eastern", "descriptor_ui": "D005202", "major_topic": false }, { "descriptor": "Genetic Predisposition to Disease", "descriptor_ui": "D020022", "major_topic": false }, { "descriptor": "Genome-Wide Association Study", "descriptor_ui": "D055106", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Lung Neoplasms", "descriptor_ui": "D008175", "major_topic": true }, { "descriptor": "Polymorphism, Single Nucleotide", "descriptor_ui": "D020641", "major_topic": false } ], "publication": { "conference_name": null, "date": "2023 May 26", "date_precision": "day", "issue": "1", "normalized_date": "2023-05-26", "pages": "3043", "proceedings_title": null, "publisher": "", "title": "Nature communications", "volume": "14", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Genome-wide association study of lung adenocarcinoma in East Asia and comparison with a European population.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Reproductive senescence is broadly observed across mammalian females, including humans, eventually leading to a loss of fertility. The pulsatile secretion of gonadotropin-releasing hormone (GnRH), which is essential for gonad function, is primarily controlled by kisspeptin neurons in the hypothalamic arcuate nucleus (ARC(kiss)), the pulse generator of GnRH. The pulsatility of GnRH release, as assessed by the amount of circulating gonadotropin, is markedly reduced in aged animals, suggesting that the malfunctions of ARC(kiss) may be responsible for reproductive aging and menopause-related disorders. However, the activity dynamics of ARC(kiss) during the natural transition to reproductive senescence remain unclear. Herein, we introduce chronic in vivo Ca(2+) imaging of ARC(kiss) in female mice by fiber photometry to monitor the synchronous episodes of ARC(kiss) (SEs(kiss)), a known hallmark of GnRH pulse generator activity, from the fully reproductive to acyclic phase over 1 year. During the reproductive phase, we find that not only the frequency, but also the intensities and waveforms of individual SEs(kiss), vary depending on the stage of the estrus cycle. During the transition to reproductive senescence, the integrity of SEs(kiss) patterns, including the frequency and waveforms, remains mostly unchanged, whereas the intensities tend to decline. These data illuminate the temporal dynamics of ARC(kiss) activities in aging female mice. More generally, our findings demonstrate the utility of fiber-photometry-based chronic imaging of neuroendocrine regulators in the brain to characterize aging-associated malfunction.", "classifications": [ { "id": "Miyamichi", "label": "Group Miyamichi", "parent": "Enomoto", "type": "group" }, { "id": "Enomoto", "label": "Team Enomoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Teppei", "last_name": "Goto", "name": null }, { "creator_type": "author", "first_name": "Mitsue", "last_name": "Hagihara", "name": null }, { "creator_type": "author", "first_name": "Kazunari", "last_name": "Miyamichi", "name": null } ], "identifiers": { "doi": { "normalized": "10.7554/elife.82533" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "37223988" } }, "mesh": [ { "descriptor": "Aging", "descriptor_ui": "D000375", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Gonadotropin-Releasing Hormone", "descriptor_ui": "D007987", "major_topic": false }, { "descriptor": "Kisspeptins", "descriptor_ui": "D059648", "major_topic": true }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": true }, { "descriptor": "Reproduction", "descriptor_ui": "D012098", "major_topic": true } ], "publication": { "conference_name": null, "date": "2023 May 24", "date_precision": "day", "issue": "", "normalized_date": "2023-05-24", "pages": "e82533", "proceedings_title": null, "publisher": "", "title": "eLife", "volume": "12", "year": 2023 }, "ssbd": { "database": [], "repository": [ "ssbd-repos-000297" ] }, "title": "Dynamics of pulsatile activities of arcuate kisspeptin neurons in aging female mice.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: Clinical trials have reported the efficacy of tropomyosin receptor kinase (TRK) inhibitors against neurotrophic receptor tyrosine kinase (NTRK) fusion gene-positive advanced solid tumors. The accumulated evidence of tumor-agnostic agent has made since TRK inhibitors were approved and used in clinical practice. Therefore, we have revised the 'Japan Society of Clinical Oncology (JSCO)/Japanese Society of Medical Oncology (JSMO)-led clinical recommendations on the diagnosis and use of tropomyosin receptor kinase inhibitors in adult and pediatric patients with neurotrophic receptor tyrosine kinase fusion-positive advanced solid tumors, cooperated by the Japanese Society of Pediatric Hematology/Oncology (JSPHO)'. METHODS: Clinical questions regarding medical care were formulated for patients with NTRK fusion-positive advanced solid tumors. Relevant publications were searched by PubMed and Cochrane Database. Critical publications and conference reports were added manually. Systematic reviews were performed for each clinical question for the purpose of developing clinical recommendations. The committee members identified by JSCO, JSMO, and JSPHO voted to determine the level of each recommendation considering the strength of evidence, expected risks and benefits to patients, and other related factors. Thereafter, a peer review by experts nominated from JSCO, JSMO, and JSPHO, and the public comments among all societies' members was done. RESULTS: The current guideline describes 3 clinical questions and 14 recommendations for whom, when, and how NTRK fusion should be tested, and what is recommended for patients with NTRK fusion-positive advanced solid tumors. CONCLUSION: The committee proposed 14 recommendations for performing NTRK testing properly to select patients who are likely to benefit from TRK inhibitors.", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yoichi", "last_name": "Naito", "name": null }, { "creator_type": "author", "first_name": "Saori", "last_name": "Mishima", "name": null }, { "creator_type": "author", "first_name": "Kiwamu", "last_name": "Akagi", "name": null }, { "creator_type": "author", "first_name": "Naomi", "last_name": "Hayashi", "name": null }, { "creator_type": "author", "first_name": "Akira", "last_name": "Hirasawa", "name": null }, { "creator_type": "author", "first_name": "Tomoro", "last_name": "Hishiki", "name": null }, { "creator_type": "author", "first_name": "Ataru", "last_name": "Igarashi", "name": null }, { "creator_type": "author", "first_name": "Masafumi", "last_name": "Ikeda", "name": null }, { "creator_type": "author", "first_name": "Shigenori", "last_name": "Kadowaki", "name": null }, { "creator_type": "author", "first_name": "Hiroaki", "last_name": "Kajiyama", "name": null }, { "creator_type": "author", "first_name": "Motohiro", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Hirotsugu", "last_name": "Kenmotsu", "name": null }, { "creator_type": "author", "first_name": "Yasuhiro", "last_name": "Kodera", "name": null }, { "creator_type": "author", "first_name": "Keigo", "last_name": "Komine", "name": null }, { "creator_type": "author", "first_name": "Takafumi", "last_name": "Koyama", "name": null }, { "creator_type": "author", "first_name": "Osamu", "last_name": "Maeda", "name": null }, { "creator_type": "author", "first_name": "Mitsuru", "last_name": "Miyachi", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Nishihara", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Nishiyama", "name": null }, { "creator_type": "author", "first_name": "Shouichi", "last_name": "Ohga", "name": null }, { "creator_type": "author", "first_name": "Wataru", "last_name": "Okamoto", "name": null }, { "creator_type": "author", "first_name": "Eiji", "last_name": "Oki", "name": null }, { "creator_type": "author", "first_name": "Shigeru", "last_name": "Ono", "name": null }, { "creator_type": "author", "first_name": "Masashi", "last_name": "Sanada", "name": null }, { "creator_type": "author", "first_name": "Ikuo", "last_name": "Sekine", "name": null }, { "creator_type": "author", "first_name": "Tadao", "last_name": "Takano", "name": null }, { "creator_type": "author", "first_name": "Kayoko", "last_name": "Tao", "name": null }, { "creator_type": "author", "first_name": "Keita", "last_name": "Terashima", "name": null }, { "creator_type": "author", "first_name": "Katsuya", "last_name": "Tsuchihara", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null }, { "creator_type": "author", "first_name": "Takayuki", "last_name": "Yoshino", "name": null }, { "creator_type": "author", "first_name": "Eishi", "last_name": "Baba", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/s10147-023-02345-7" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "37212982" } }, "mesh": [ { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Child", "descriptor_ui": "D002648", "major_topic": false }, { "descriptor": "East Asian People", "descriptor_ui": "D000095225", "major_topic": false }, { "descriptor": "Gene Fusion", "descriptor_ui": "D050939", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Japan", "descriptor_ui": "D007564", "major_topic": false }, { "descriptor": "Neoplasms", "descriptor_ui": "D009369", "major_topic": true }, { "descriptor": "Protein Kinase Inhibitors", "descriptor_ui": "D047428", "major_topic": false }, { "descriptor": "Receptor Protein-Tyrosine Kinases", "descriptor_ui": "D020794", "major_topic": true }, { "descriptor": "Receptor, trkA", "descriptor_ui": "D020917", "major_topic": false }, { "descriptor": "Tropomyosin", "descriptor_ui": "D014335", "major_topic": true } ], "publication": { "conference_name": null, "date": "2023 May 22", "date_precision": "day", "issue": "", "normalized_date": "2023-05-22", "pages": "", "proceedings_title": null, "publisher": "", "title": "International journal of clinical oncology", "volume": "", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Japanese Society of Medical Oncology/Japan Society of Clinical Oncology/Japanese Society of Pediatric Hematology/Oncology-led clinical recommendations on the diagnosis and use of tropomyosin receptor kinase inhibitors in adult and pediatric patients with neurotrophic receptor tyrosine kinase fusion-positive advanced solid tumors.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Nuclear magnetic resonance (NMR) spectroscopy is one of the indispensable techniques in chemistry because it enables us to obtain accurate information on the chemical, electronic, and dynamic properties of molecules. Computational simulation of the NMR spectra requires time-consuming density functional theory (DFT) calculations for an ensemble of molecular conformations. For large flexible molecules, it is considered too high-cost since it requires time-averaging of the instantaneous chemical shifts of each nuclear spin across the conformational space of molecules for NMR timescales. Here, we present a Gaussian process/deep kernel learning-based machine learning (ML) method for enabling us to predict, average in time, and analyze the instantaneous chemical shifts of conformations in the molecular dynamics trajectory. We demonstrate the use of the method by computing the averaged 1H and 13C chemical shifts of each nuclear spin of a trefoil knot molecule consisting of 24 para-connected benzene rings (240 atoms). By training ML model with the chemical shift data obtained from DFT calculations, we predicted chemical shifts for each conformation during dynamics. We were able to observe the merging of the time-averaged chemical shifts of each nuclear spin in a singlet 1H NMR peak and two 13C NMR peaks for the knot molecule, in agreement with experimental measurements. The unique feature of the presented method is the use of the learned low-dimensional deep kernel representation of local spin environments for comparing and analyzing the local chemical environment histories of spins during dynamics. It allowed us to identify two groups of protons in the knot molecule, which implies that the observed singlet 1H NMR peak could be composed of the contributions from protons with two distinct local chemical environments.", "classifications": [ { "id": "Hijikata", "label": "Group Hijikata", "parent": "Tsuchiya", "type": "group" }, { "id": "Tsuchiya", "label": "Team Tsuchiya", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Mikhail", "last_name": "Tsitsvero", "name": null }, { "creator_type": "author", "first_name": "Jenny", "last_name": "Pirillo", "name": null }, { "creator_type": "author", "first_name": "Yuh", "last_name": "Hijikata", "name": null }, { "creator_type": "author", "first_name": "Tamiki", "last_name": "Komatsuzaki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1063/5.0147398" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "37194718" } }, "mesh": [], "publication": { "conference_name": null, "date": "2023 May 21", "date_precision": "day", "issue": "19", "normalized_date": "2023-05-21", "pages": "194108", "proceedings_title": null, "publisher": "", "title": "The Journal of chemical physics", "volume": "158", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "NMR spectrum prediction for dynamic molecules by machine learning: A case study of trefoil knot molecule.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "OBJECTIVES: We evaluated the potential of preoperative fluorine-18-fluorodeoxyglucose positron emission tomography (18F-FDG PET) to predict invasive thymic epithelial tumours in patients with computed tomography (CT)-defined clinical stage I thymic epithelial tumours I thymic epithelial tumours from pathological stage I (best cut-off value, 4.2; area under the curve [AUC] = 0.820) and thymic carcinomas from other thymic tumours (best cut-off value, 4.5; AUC = 0.882). CONCLUSIONS: Thoracic surgeons should carefully determine the surgical approach for high FDG-uptake thymic epithelial tumours and keep in mind the issues associated with thymic carcinoma and potential combined resections of neighbouring structures.", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Takaki", "last_name": "Akamine", "name": null }, { "creator_type": "author", "first_name": "Kazuo", "last_name": "Nakagawa", "name": null }, { "creator_type": "author", "first_name": "Kimiteru", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Hirokazu", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Masaya", "last_name": "Yotsukura", "name": null }, { "creator_type": "author", "first_name": "Yukihiro", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null }, { "creator_type": "author", "first_name": "Masahiko", "last_name": "Kusumoto", "name": null }, { "creator_type": "author", "first_name": "Shun-Ichi", "last_name": "Watanabe", "name": null } ], "identifiers": { "doi": { "normalized": "10.1093/icvts/ivad082" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "37208183" } }, "mesh": [], "publication": { "conference_name": null, "date": "2023 May 19", "date_precision": "day", "issue": "", "normalized_date": "2023-05-19", "pages": "ivad082", "proceedings_title": null, "publisher": "", "title": "Interdisciplinary cardiovascular and thoracic surgery", "volume": "", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Role of 18F-FDG PET in selecting candidates for a minimally invasive approach for thymic epithelial tumour resection.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Cancer chemoresistance is often attributed to slow-cycling persister populations with cancer stem cell (CSC)-like features. However, how persister populations emerge and prevail in cancer remains obscure. We previously demonstrated that while the NOX1-mTORC1 pathway is responsible for proliferation of a fast-cycling CSC population, PROX1 expression is required for chemoresistant persisters in colon cancer. Here, we show that enhanced autolysosomal activity mediated by mTORC1 inhibition induces PROX1 expression and that PROX1 induction in turn inhibits NOX1-mTORC1 activation. CDX2, identified as a transcriptional activator of NOX1, mediates PROX1-dependent NOX1 inhibition. PROX1-positive and CDX2-positive cells are present in distinct populations, and mTOR inhibition triggers conversion of the CDX2-positive population to the PROX1-positive population. Inhibition of autophagy synergizes with mTOR inhibition to block cancer proliferation. Thus, mTORC1 inhibition-mediated induction of PROX1 stabilizes a persister-like state with high autolysosomal activity via a feedback regulation that involves a key cascade of proliferating CSCs.", "classifications": [ { "id": "Hamamoto", "label": "Group Hamamoto", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Group Okamoto", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Hirokazu", "last_name": "Ohata", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Shiokawa", "name": null }, { "creator_type": "author", "first_name": "Hiroaki", "last_name": "Sakai", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Kanda", "name": null }, { "creator_type": "author", "first_name": "Yoshie", "last_name": "Okimoto", "name": null }, { "creator_type": "author", "first_name": "Syuzo", "last_name": "Kaneko", "name": null }, { "creator_type": "author", "first_name": "Ryuji", "last_name": "Hamamoto", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Nakagama", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Okamoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.celrep.2023.112519" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "37224811" } }, "mesh": [ { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Cell Proliferation", "descriptor_ui": "D049109", "major_topic": false }, { "descriptor": "Colonic Neoplasms", "descriptor_ui": "D003110", "major_topic": true }, { "descriptor": "Feedback", "descriptor_ui": "D005246", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mechanistic Target of Rapamycin Complex 1", "descriptor_ui": "D000076222", "major_topic": false }, { "descriptor": "NADPH Oxidase 1", "descriptor_ui": "D000074624", "major_topic": false }, { "descriptor": "Prospero-Related Homeobox 1 Protein", "descriptor_ui": "D000098551", "major_topic": false } ], "publication": { "conference_name": null, "date": "2023 May 17", "date_precision": "day", "issue": "", "normalized_date": "2023-05-17", "pages": "112519", "proceedings_title": null, "publisher": "", "title": "Cell reports", "volume": "", "year": 2023 }, "ssbd": { "database": [], "repository": [ "ssbd-repos-000400" ] }, "title": "PROX1 induction by autolysosomal activity stabilizes persister-like state of colon cancer via feedback repression of the NOX1-mTORC1 pathway.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Alzheimer's disease (AD) is a progressive neurodegenerative disorder whereby oxidative stress augmentation results in mitochondrial dysfunction and cell death by apoptosis. Emerging evidence indicates that reactive sulfur species (RSS), such as glutathione hydropersulfide (GSSH), is endogenously produced, functions as potent antioxidants, and regulate redox signaling through the formation of protein polysulfides. However, the relationship between RSS and AD pathogenesis is not fully understood. In this study, we analyzed endogenous RSS production in the brain tissue of a familial AD model (5xFAD) mouse using multiple RSS-omics approaches. Memory impairment, increased amyloid plaques, and neuroinflammation have been confirmed in 5xFAD mice. Quantitative RSS omics analysis revealed that the total polysulfide content was significantly decreased in the brains of 5xFAD mice, whereas there was no significant difference in the levels of glutathione, GSSH, or hydrogen sulfide between wild-type and 5xFAD mice. In contrast, a significant decline in the protein polysulfide status was observed in the brains of 5xFAD mice, suggesting that RSS production and subsequent redox signaling might be altered during the onset and progression of AD. Our findings have important implications for understanding the significance of RSS in the development of preventive and therapeutic strategies for AD.", "classifications": [ { "id": "JPMJCR2024", "label": "JPMJCR2024", "researcher": "Motohiro Nishida", "type": "grant" }, { "id": "Akaike", "label": "Group Akaike", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Group Nishida", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Ayaka", "last_name": "Kinno", "name": null }, { "creator_type": "author", "first_name": "Shingo", "last_name": "Kasamatsu", "name": null }, { "creator_type": "author", "first_name": "Takaaki", "last_name": "Akaike", "name": null }, { "creator_type": "author", "first_name": "Hideshi", "last_name": "Ihara", "name": null } ], "identifiers": { "doi": { "normalized": "10.3390/antiox12051105" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "37237971" } }, "mesh": [], "publication": { "conference_name": null, "date": "2023 May 16", "date_precision": "day", "issue": "5", "normalized_date": "2023-05-16", "pages": "1105", "proceedings_title": null, "publisher": "", "title": "Antioxidants (Basel, Switzerland)", "volume": "12", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Reactive Sulfur Species Omics Analysis in the Brain Tissue of the 5xFAD Mouse Model of Alzheimer's Disease.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Although the development of three-dimensional (3D) printing technology is growing rapidly in the biomedical field, it remains a challenge to achieve arbitrary 3D structures with high resolution and high efficiency. Protein hydrogels fabricated by twophoton polymerization (TPP) have excellent mechanical properties, high precision, and 3D architecture. However, a large number of the amino acid group in bovine serum albumin (BSA) would be consumed when the protein-based hydrogels use dyes of free radical type II photoinitiators. In this study, we use glycidyl methacrylate (GMA) to modify BSA molecules to obtain a series of BSA-GMA materials, allowing the protein material to be two-photon polymerized with a water-soluble free radical type I photoinitiator. The precisely controllable 3D structure of the BSA-GMA hydrogel was fabricated by adjusting the concentration of the precursor solution, the degree of methacrylation, and the processing parameters of the TPP technique. Importantly, BSA-GMA materials are free of acidic hazardous substances. Meanwhile, the water-soluble initiator lithium phenyl (2,4,6-trimethylbenzoyl) phosphite (LAP) allows TPP on the vinyl group of the GMA chain and thus without consuming its amino acid group. The as-prepared BSA-GMA hydrogel structure exhibits excellent autofluorescence imaging, pH responsiveness, and biocompatibility, which would provide new avenues for potential applications in tissue engineering and biomedical fields to meet specific biological requirements.", "classifications": [ { "id": "Fujita", "label": "Group Fujita", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Teng", "last_name": "Li", "name": null }, { "creator_type": "author", "first_name": "Jie", "last_name": "Liu", "name": null }, { "creator_type": "author", "first_name": "Min", "last_name": "Guo", "name": null }, { "creator_type": "author", "first_name": "Fan-Chun", "last_name": "Bin", "name": null }, { "creator_type": "author", "first_name": "Jian-Yu", "last_name": "Wang", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Nakayama", "name": null }, { "creator_type": "author", "first_name": "Wei-Cai", "last_name": "Zhang", "name": null }, { "creator_type": "author", "first_name": "Feng", "last_name": "Jin", "name": null }, { "creator_type": "author", "first_name": "Xian-Zi", "last_name": "Dong", "name": null }, { "creator_type": "author", "first_name": "Katsumasa", "last_name": "Fujita", "name": null }, { "creator_type": "author", "first_name": "Mei-Ling", "last_name": "Zheng", "name": null } ], "identifiers": { "doi": { "normalized": "10.18063/ijb.752" }, "pmcid": { "normalized": null }, "pmid": { "normalized": null } }, "mesh": [], "publication": { "conference_name": null, "date": "2023-05-12", "date_precision": "day", "issue": "", "normalized_date": "2023-05-12", "pages": "", "proceedings_title": null, "publisher": "", "title": "International Journal of Bioprinting", "volume": "", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Synthesis of biocompatible BSA-GMA and two-photon polymerization of 3D hydrogels with free radical type I photoinitiator", "url": "https://ijb.whioce.com/index.php/int-j-bioprinting/article/view/752", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Decentralized stochastic control (DSC) is a stochastic optimal control problem consisting of multiple controllers. DSC assumes that each controller is unable to accurately observe the target system and the other controllers. This setup results in two difficulties in DSC; one is that each controller has to memorize the infinite-dimensional observation history, which is not practical, because the memory of the actual controllers is limited. The other is that the reduction of infinite-dimensional sequential Bayesian estimation to finite-dimensional Kalman filter is impossible in general DSC, even for linear-quadratic-Gaussian (LQG) problems. In order to address these issues, we propose an alternative theoretical framework to DSC-memory-limited DSC (ML-DSC). ML-DSC explicitly formulates the finite-dimensional memories of the controllers. Each controller is jointly optimized to compress the infinite-dimensional observation history into the prescribed finite-dimensional memory and to determine the control based on it. Therefore, ML-DSC can be a practical formulation for actual memory-limited controllers. We demonstrate how ML-DSC works in the LQG problem. The conventional DSC cannot be solved except in the special LQG problems where the information the controllers have is independent or partially nested. We show that ML-DSC can be solved in more general LQG problems where the interaction among the controllers is not restricted.", "classifications": [ { "id": "Kobayashi", "label": "Group Kobayashi", "parent": "Wakamoto", "type": "group" }, { "id": "Wakamoto", "label": "Team Wakamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Takehiro", "last_name": "Tottori", "name": null }, { "creator_type": "author", "first_name": "Tetsuya J.", "last_name": "Kobayashi", "name": null } ], "identifiers": { "doi": { "normalized": "10.3390/e25050791" }, "pmcid": { "normalized": "PMC10217446" }, "pmid": { "normalized": "37238546" } }, "mesh": [], "publication": { "conference_name": null, "date": "2023 May 12", "date_precision": "day", "issue": "5", "normalized_date": "2023-05-12", "pages": "", "proceedings_title": null, "publisher": "", "title": "Entropy (Basel, Switzerland)", "volume": "25", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Decentralized Stochastic Control with Finite-Dimensional Memories: A Memory Limitation Approach.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Remdesivir is an antiviral drug used for COVID-19 treatment worldwide. Cardiovascular side effects have been associated with remdesivir; however, the underlying molecular mechanism remains unknown. Here, we performed a large-scale G-protein-coupled receptor screening in combination with structural modeling and found that remdesivir is a selective, partial agonist for urotensin-II receptor (UTS2R) through the Galpha(i/o)-dependent AKT/ERK axis. Functionally, remdesivir treatment induced prolonged field potential and APD(90) in human induced pluripotent stem cell (iPS)-derived cardiomyocytes and impaired contractility in both neonatal and adult cardiomyocytes, all of which mirror the clinical pathology. Importantly, remdesivir-mediated cardiac malfunctions were effectively attenuated by antagonizing UTS2R signaling. Finally, we characterized the effect of 110 single-nucleotide variants in UTS2R gene reported in genome database and found four missense variants that show gain-of-function effects in the receptor sensitivity to remdesivir. Collectively, our study illuminates a previously unknown mechanism underlying remdesivir-related cardiovascular events and that genetic variations of UTS2R gene can be a potential risk factor for cardiovascular events during remdesivir treatment, which collectively paves the way for a therapeutic opportunity to prevent such events in the future.", "classifications": [ { "id": "JPMJCR2024", "label": "JPMJCR2024", "researcher": "Motohiro Nishida", "type": "grant" }, { "id": "Nishida", "label": "Group Nishida", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Akiko", "last_name": "Ogawa", "name": null }, { "creator_type": "author", "first_name": "Seiya", "last_name": "Ohira", "name": null }, { "creator_type": "author", "first_name": "Yuri", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Ikuta", "name": null }, { "creator_type": "author", "first_name": "Shota", "last_name": "Yanagida", "name": null }, { "creator_type": "author", "first_name": "Xinya", "last_name": "Mi", "name": null }, { "creator_type": "author", "first_name": "Yukina", "last_name": "Ishii", "name": null }, { "creator_type": "author", "first_name": "Yasunari", "last_name": "Kanda", "name": null }, { "creator_type": "author", "first_name": "Motohiro", "last_name": "Nishida", "name": null }, { "creator_type": "author", "first_name": "Asuka", "last_name": "Inoue", "name": null }, { "creator_type": "author", "first_name": "Fan-Yan", "last_name": "Wei", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s42003-023-04888-x" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "37173432" } }, "mesh": [ { "descriptor": "Adenosine Monophosphate", "descriptor_ui": "D000249", "major_topic": false }, { "descriptor": "Alanine", "descriptor_ui": "D000409", "major_topic": false }, { "descriptor": "Antiviral Agents", "descriptor_ui": "D000998", "major_topic": true }, { "descriptor": "COVID-19", "descriptor_ui": "D000086382", "major_topic": true }, { "descriptor": "COVID-19 Drug Treatment", "descriptor_ui": "D000093485", "major_topic": false }, { "descriptor": "Heart Failure", "descriptor_ui": "D006333", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Induced Pluripotent Stem Cells", "descriptor_ui": "D057026", "major_topic": true }, { "descriptor": "Infant, Newborn", "descriptor_ui": "D007231", "major_topic": false }, { "descriptor": "Myocytes, Cardiac", "descriptor_ui": "D032383", "major_topic": false }, { "descriptor": "Receptors, G-Protein-Coupled", "descriptor_ui": "D043562", "major_topic": true } ], "publication": { "conference_name": null, "date": "2023 May 12", "date_precision": "day", "issue": "1", "normalized_date": "2023-05-12", "pages": "511", "proceedings_title": null, "publisher": "", "title": "Communications biology", "volume": "6", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Activation of the urotensin-II receptor by remdesivir induces cardiomyocyte dysfunction.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Animals are capable of representing different scale spaces from smaller to larger ones. However, most laboratory animals live their life in a narrow range of scale spaces like home-cages and experimental setups, making it hard to extrapolate the spatial representation and learning process in large scale spaces from those in conventional scale spaces. Here, we developed a 3-meter diameter Barnes maze (BM3), then explored whether spatial learning in the Barnes maze (BM) is calibrated by scale spaces. Spatial learning in the BM3 was successfully established with a lower learning rate than that in a conventional 1-meter diameter Barnes maze (BM1). Specifically, analysis of exploration strategies revealed that the mice in the BM3 persistently searched certain places throughout the learning, while such places were rapidly decreased in the BM1. These results suggest dedicated exploration strategies requiring more trial-and-errors and computational resources in the BM3 than in the BM1, leading to a divergence of spatial learning between the BM1 and the BM3. We then explored whether prior learning in one BM scale calibrates subsequent spatial learning in another BM scale, and found asymmetric facilitation such that the prior learning in the BM3 facilitated the subsequent BM1 learning, but not vice versa Thus, scale space calibrates both the present and subsequent BM learning. This is the first study to demonstrate scale-dependent spatial learning in BM in mice. The couple of the BM1 and the BM3 would be a suitable system to seek how animals represent different scale spaces with underlying neural implementation.Significance StatementAnimals are capable of representing different scale spaces. However, whether scale space calibrates goal-directed spatial learning remains unclear. The Barnes maze is a well-established experimental paradigm to evaluate spatial learning in rodents. Here, we developed a larger scale 3-meter diameter Barnes maze (BM3) then compared various navigation features in mice between the BM3 and a conventional 1-meter diameter Barnes maze (BM1). We demonstrated that spatial learning on the BM3 was established, but required more trial-and-error and computational resources than in the BM1, prompting mice to visit certain places persistently. Such learning experiences in the BM3 facilitated subsequent spatial learning in the BM1, but not vice versa. These results suggest that scale space calibrates present and subsequent spatial learning.", "classifications": [ { "id": "JPMJCR1921", "label": "JPMJCR1921", "researcher": "Itaru Imayoshi", "type": "grant" }, { "id": "Imayoshi", "label": "Group Imayoshi", "parent": "Imayoshi", "type": "group" }, { "id": "Imayoshi", "label": "Team Imayoshi", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yuto", "last_name": "Tachiki", "name": null }, { "creator_type": "author", "first_name": "Yusuke 2nd", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Mutsumi", "last_name": "Kurahashi", "name": null }, { "creator_type": "author", "first_name": "Keisuke", "last_name": "Oki", "name": null }, { "creator_type": "author", "first_name": "Ozgun", "last_name": "Mavuk", "name": null }, { "creator_type": "author", "first_name": "Takuma", "last_name": "Nakagawa", "name": null }, { "creator_type": "author", "first_name": "Shogo", "last_name": "Ishihara", "name": null }, { "creator_type": "author", "first_name": "Yuichiro", "last_name": "Gyoten", "name": null }, { "creator_type": "author", "first_name": "Akira", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Itaru", "last_name": "Imayoshi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1523/eneuro.0505-22.2023" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "37169582" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Maze Learning", "descriptor_ui": "D018782", "major_topic": false }, { "descriptor": "Memory", "descriptor_ui": "D008568", "major_topic": true }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Spatial Learning", "descriptor_ui": "D065853", "major_topic": true } ], "publication": { "conference_name": null, "date": "2023 May 11", "date_precision": "day", "issue": "", "normalized_date": "2023-05-11", "pages": "ENEURO.0505-22.2023", "proceedings_title": null, "publisher": "", "title": "eNeuro", "volume": "", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Scale space calibrates present and subsequent spatial learning in Barnes maze in mice.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Root penetration into the soil is essential for plants to access water and nutrients, as well as to mechanically support aboveground structures. This requires a combination of healthy plant growth, adequate soil mechanical properties, and compatible plant-soil interactions. Despite the current knowledge of the static rheology driving the interactions at the root-soil interface, few theoretical approaches have attempted to describe root penetration with dynamic rheology. In this work, we experimentally showed that radish roots in contact with soil of specific density during a specific growth stage fail to penetrate the soil. To explore the mechanism of root penetration into the soil, we constructed a theoretical model to explore the relevant conditions amenable to root entry into the soil. The theory indicates that dimensionless parameters such as root growth anisotropy, static root-soil competition, and dynamic root-soil competition are important for root penetration. The consequent theoretical expectations were supported by finite element analysis, and a potential mechanism of root penetration into the soil is discussed.", "classifications": [ { "id": "JPMJCR2121", "label": "JPMJCR2121", "researcher": "Minako Ueda", "type": "grant" }, { "id": "Tsugawa", "label": "Group Tsugawa", "parent": "Ueda", "type": "group" }, { "id": "Ueda", "label": "Group Ueda", "parent": "Ueda", "type": "group" }, { "id": "Ueda", "label": "Team Ueda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Haruka", "last_name": "Tomobe", "name": null }, { "creator_type": "author", "first_name": "Satoru", "last_name": "Tsugawa", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Tetsuya", "last_name": "Arita", "name": null }, { "creator_type": "author", "first_name": "Allen Yi-Lun", "last_name": "Tsai", "name": null }, { "creator_type": "author", "first_name": "Minoru", "last_name": "Kubo", "name": null }, { "creator_type": "author", "first_name": "Taku", "last_name": "Demura", "name": null }, { "creator_type": "author", "first_name": "Shinichiro", "last_name": "Sawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41598-023-34025-x" }, "pmcid": { "normalized": "PMC10170176" }, "pmid": { "normalized": "37160914" } }, "mesh": [ { "descriptor": "Anisotropy", "descriptor_ui": "D016880", "major_topic": false }, { "descriptor": "Finite Element Analysis", "descriptor_ui": "D020342", "major_topic": false }, { "descriptor": "Plant Roots", "descriptor_ui": "D018517", "major_topic": false }, { "descriptor": "Soil", "descriptor_ui": "D012987", "major_topic": true } ], "publication": { "conference_name": null, "date": "2023 May 9", "date_precision": "day", "issue": "1", "normalized_date": "2023-05-09", "pages": "7473", "proceedings_title": null, "publisher": "", "title": "Scientific reports", "volume": "13", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "A mechanical theory of competition between plant root growth and soil pressure reveals a potential mechanism of root penetration.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Kallikrein-related peptides (KLKs) form an evolutionally conserved subgroup of secreted serine proteases that consists of 15 members (KLK1-15). Previous studies have shown that KLKs regulate diverse biological processes, but the clinical significance of KLKs remains largely unclear in human breast cancers. We examined the expression profile of 15 KLK genes in breast carcinomas using microarray data. Next, we immunolocalized KLK12 in 140 breast carcinomas and evaluated its clinical significance. Subsequently, we examined the effects of KLK12 on proliferation and migration in breast cancer cell lines. From microarray analyses, it turned out that KLK12 was the most strongly associated with low-grade malignancy in breast carcinomas among the 15 KLK members. Immunohistochemical KLK12 status was positively associated with ER and PR status, while it was inversely associated with stage, pathological T factor, lymph node metastasis, and distant metastasis. Prognostic analyses demonstrated that KLK12 was a favorable prognostic factor for both disease-free and breast cancer-specific survival of the patients. Furthermore, the knockdown of KLK12 significantly increased cell proliferation activity and cell migration of breast cancer cells. These results suggest that KLK12 has antitumorigenic effects associated with proliferation and migration and immunohistochemical KLK12 status as a potent favorable prognostic factor in breast carcinoma patients.", "classifications": [ { "id": "Suzuki", "label": "Group Suzuki", "parent": "Takekawa", "type": "group" }, { "id": "Takekawa", "label": "Team Takekawa", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Ai", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Kiyoshi", "last_name": "Takagi", "name": null }, { "creator_type": "author", "first_name": "Ayano", "last_name": "Yoshimura", "name": null }, { "creator_type": "author", "first_name": "Wakana", "last_name": "Tsukamoto", "name": null }, { "creator_type": "author", "first_name": "Mio", "last_name": "Yamaguchi-Tanaka", "name": null }, { "creator_type": "author", "first_name": "Yasuhiro", "last_name": "Miki", "name": null }, { "creator_type": "author", "first_name": "Akiko", "last_name": "Ebata", "name": null }, { "creator_type": "author", "first_name": "Minoru", "last_name": "Miyashita", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Suzuki", "name": null } ], "identifiers": { "doi": { "normalized": "10.3390/ijms24098419" }, "pmcid": { "normalized": "PMC10179240" }, "pmid": { "normalized": "37176127" } }, "mesh": [ { "descriptor": "Breast Neoplasms", "descriptor_ui": "D001943", "major_topic": true }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Kallikreins", "descriptor_ui": "D007610", "major_topic": false }, { "descriptor": "Prognosis", "descriptor_ui": "D011379", "major_topic": false } ], "publication": { "conference_name": null, "date": "2023 May 8", "date_precision": "day", "issue": "9", "normalized_date": "2023-05-08", "pages": "", "proceedings_title": null, "publisher": "", "title": "International journal of molecular sciences", "volume": "24", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Kallikrein-Related Peptidase 12 (KLK12) in Breast Cancer as a Favorable Prognostic Marker.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Tissue engineers have utilized a variety of three-dimensional (3D) scaffolds for controlling multicellular dynamics and the resulting tissue microstructures. In particular, cutting-edge microfabrication technologies, such as 3D bioprinting, provide increasingly complex structures. However, unpredictable microtissue detachment from scaffolds, which ruins desired tissue structures, is becoming an evident problem. To overcome this issue, we elucidated the mechanism underlying collective cellular detachment by combining a new computational simulation method with quantitative tissue-culture experiments. We first quantified the stochastic processes of cellular detachment shown by vascular smooth muscle cells on model curved scaffolds and found that microtissue morphologies vary drastically depending on cell contractility, substrate curvature, and cell-substrate adhesion strength. To explore this mechanism, we developed a new particle-based model that explicitly describes stochastic processes of multicellular dynamics, such as adhesion, rupture, and large deformation of microtissues on structured surfaces. Computational simulations using the developed model successfully reproduced characteristic detachment processes observed in experiments. Crucially, simulations revealed that cellular contractility-induced stress is locally concentrated at the cell-substrate interface, subsequently inducing a catastrophic process of collective cellular detachment, which can be suppressed by modulating cell contractility, substrate curvature, and cell-substrate adhesion. These results show that the developed computational method is useful for predicting engineered tissue dynamics as a platform for prediction-guided scaffold design. STATEMENT OF SIGNIFICANCE: Microfabrication technologies aiming to control multicellular dynamics by engineering 3D scaffolds are attracting increasing attention for modelling in cell biology and regenerative medicine. However, obtaining microtissues with the desired 3D structures is made considerably more difficult by microtissue detachments from scaffolds. This study reveals a key mechanism behind this detachment by developing a novel computational method for simulating multicellular dynamics on designed scaffolds. This method enabled us to predict microtissue dynamics on structured surfaces, based on cell mechanics, substrate geometry, and cell-substrate interaction. This study provides a platform for the physics-based design of micro-engineered scaffolds and thus contributes to prediction-guided biomaterials design in the future.", "classifications": [ { "id": "JPMJCR1921", "label": "JPMJCR1921", "researcher": "Itaru Imayoshi", "type": "grant" }, { "id": "Imayoshi", "label": "Group Imayoshi", "parent": "Imayoshi", "type": "group" }, { "id": "Okuda", "label": "Group Okuda", "parent": "Imayoshi", "type": "group" }, { "id": "Imayoshi", "label": "Team Imayoshi", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Ryosuke", "last_name": "Matsuzawa", "name": null }, { "creator_type": "author", "first_name": "Akira", "last_name": "Matsuo", "name": null }, { "creator_type": "author", "first_name": "Shuya", "last_name": "Fukamachi", "name": null }, { "creator_type": "author", "first_name": "Sho", "last_name": "Shimada", "name": null }, { "creator_type": "author", "first_name": "Midori", "last_name": "Takeuchi", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Nishina", "name": null }, { "creator_type": "author", "first_name": "Philip", "last_name": "Kollmannsberger", "name": null }, { "creator_type": "author", "first_name": "Ryo", "last_name": "Sudo", "name": null }, { "creator_type": "author", "first_name": "Satoru", "last_name": "Okuda", "name": null }, { "creator_type": "author", "first_name": "Tadahiro", "last_name": "Yamashita", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.actbio.2023.05.012" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "37164300" } }, "mesh": [ { "descriptor": "Cell Adhesion", "descriptor_ui": "D002448", "major_topic": false }, { "descriptor": "Microtechnology", "descriptor_ui": "D055616", "major_topic": false }, { "descriptor": "Myocytes, Smooth Muscle", "descriptor_ui": "D032389", "major_topic": true }, { "descriptor": "Tissue Engineering", "descriptor_ui": "D023822", "major_topic": true }, { "descriptor": "Tissue Scaffolds", "descriptor_ui": "D054457", "major_topic": false } ], "publication": { "conference_name": null, "date": "2023 May 8", "date_precision": "day", "issue": "", "normalized_date": "2023-05-08", "pages": "S1742-7061(23)00260-X", "proceedings_title": null, "publisher": "", "title": "Acta biomaterialia", "volume": "", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Multicellular dynamics on structured surfaces: Stress concentration is a key to controlling complex microtissue morphology on engineered scaffolds.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Collective cell migration is the coordinated movement of multiple cells connected with cadherin-based adherens junctions essential for physiological and pathological processes. Cadherins undergo dynamic intracellular trafficking and their surface level is determined by a balance between endocytosis, recycling and degradation. However, the regulatory mechanism of cadherin turnover in collective cell migration remains elusive. In this study, we show that a BAR domain protein pacsin 2 plays an essential role in collective cell migration by regulating the N-cadherin endocytosis in human cancer cells. Pacsin 2-depleted cells formed cell-cell contacts enriched with N-cadherin and migrated in a directed manner. Furthermore, pacsin 2-depleted cells showed attenuated internalization of N-cadherin from the cell surface. Interestingly, the GST-pulldown assay demonstrated that the pacsin 2 SH3 domain binds to the cytoplasmic region of N-cadherin, and expression of an N-cadherin mutant defective in binding to pacsin 2 phenocopied pacsin 2 RNAi cells both in cell contact formation and N-cadherin endocytosis. These data support new insights into a novel endocytic route of N-cadherin in collective cell migration providing pacsin 2 as a possible therapeutic target for cancer metastasis.", "classifications": [ { "id": "Higaki", "label": "Group Higaki", "parent": "Ueda", "type": "group" }, { "id": "Ueda", "label": "Team Ueda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Haymar", "last_name": "Wint", "name": null }, { "creator_type": "author", "first_name": "Jianzhen", "last_name": "Li", "name": null }, { "creator_type": "author", "first_name": "Tadashi", "last_name": "Abe", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Yamada", "name": null }, { "creator_type": "author", "first_name": "Takumi", "last_name": "Higaki", "name": null }, { "creator_type": "author", "first_name": "Yasutomo", "last_name": "Nasu", "name": null }, { "creator_type": "author", "first_name": "Masami", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Kohji", "last_name": "Takei", "name": null }, { "creator_type": "author", "first_name": "Tetsuya", "last_name": "Takeda", "name": null } ], "identifiers": { "doi": { "normalized": "10.1242/jcs.260827" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "37132654" } }, "mesh": [ { "descriptor": "Adaptor Proteins, Signal Transducing", "descriptor_ui": "D048868", "major_topic": true }, { "descriptor": "Adherens Junctions", "descriptor_ui": "D022005", "major_topic": false }, { "descriptor": "Cadherins", "descriptor_ui": "D015820", "major_topic": true }, { "descriptor": "Cell Membrane", "descriptor_ui": "D002462", "major_topic": false }, { "descriptor": "Cell Movement", "descriptor_ui": "D002465", "major_topic": false }, { "descriptor": "Endocytosis", "descriptor_ui": "D004705", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Neoplasms", "descriptor_ui": "D009369", "major_topic": true } ], "publication": { "conference_name": null, "date": "2023 May 3", "date_precision": "day", "issue": "", "normalized_date": "2023-05-03", "pages": "jcs.260827", "proceedings_title": null, "publisher": "", "title": "Journal of cell science", "volume": "", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Pacsin 2-dependent N-cadherin internalization regulates the migration behaviour of malignant cancer cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The journey to implement cancer genomic medicine (CGM) in oncology practice began in the 1980s, which is considered the dawn of genetic and genomic cancer research. At the time, a variety of activating oncogenic alterations and their functional significance were unveiled in cancer cells, which led to the development of molecular targeted therapies in the 2000s and beyond. Although CGM is still a relatively new discipline and it is difficult to predict to what extent CGM will benefit the diverse pool of cancer patients, the National Cancer Center (NCC) of Japan has already contributed considerably to CGM advancement for the conquest of cancer. Looking back at these past achievements of the NCC, we predict that the future of CGM will involve the following: 1) A biobank of paired cancerous and non-cancerous tissues and cells from various cancer types and stages will be developed. The quantity and quality of these samples will be compatible with omics analyses. All biobank samples will be linked to longitudinal clinical information. 2) New technologies, such as whole-genome sequencing and artificial intelligence, will be introduced and new bioresources for functional and pharmacologic analyses (e.g., a patient-derived xenograft library) will be systematically deployed. 3) Fast and bidirectional translational research (bench-to-bedside and bedside-to-bench) performed by basic researchers and clinical investigators, preferably working alongside each other at the same institution, will be implemented; 4) Close collaborations between academia, industry, regulatory bodies, and funding agencies will be established. 5) There will be an investment in the other branch of CGM, personalized preventive medicine, based on the individual's genetic predisposition to cancer.", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Teruhiko", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null }, { "creator_type": "author", "first_name": "Ken", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Genichiro", "last_name": "Ishii", "name": null }, { "creator_type": "author", "first_name": "Akinobu", "last_name": "Hamada", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Mano", "name": null }, { "creator_type": "author", "first_name": "Kuniko", "last_name": "Sunami", "name": null }, { "creator_type": "author", "first_name": "Noboru", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Kohno", "name": null } ], "identifiers": { "doi": { "normalized": "10.20892/j.issn.2095-3941.2023.0036" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "37133223" } }, "mesh": [ { "descriptor": "Artificial Intelligence", "descriptor_ui": "D001185", "major_topic": true }, { "descriptor": "Genomic Medicine", "descriptor_ui": "D000088744", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Japan", "descriptor_ui": "D007564", "major_topic": false }, { "descriptor": "Medical Oncology", "descriptor_ui": "D008495", "major_topic": false }, { "descriptor": "Neoplasms", "descriptor_ui": "D009369", "major_topic": true } ], "publication": { "conference_name": null, "date": "2023 May 3", "date_precision": "day", "issue": "", "normalized_date": "2023-05-03", "pages": "j.issn.2095-3941.2023.0036", "proceedings_title": null, "publisher": "", "title": "Cancer biology & medicine", "volume": "", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "The evolution of cancer genomic medicine in Japan and the role of the National Cancer Center Japan.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Epigenetic alterations, especially histone methylation, are key factors in cell migration and invasion in cancer metastasis. However, in lung cancer metastasis, the mechanism by which histone methylation regulates metastasis has not been fully elucidated. Here, we found that the histone methyltransferase SMYD2 is overexpressed in lung cancer and that knockdown of SMYD2 could reduce the rates of cell migration and invasion in lung cancer cell lines via direct downregulation of SMAD3 via SMYD2-mediated epigenetic regulation. Furthermore, using an in vitro epithelial-mesenchymal transition (EMT) system with a Transwell system, we generated highly invasive H1299 (In-H1299) cell lines and observed the suppression of metastatic features by SMYD2 knockdown. Finally, two types of in vivo studies revealed that the formation of metastatic tumors by shSMYD2 was significantly suppressed. Thus, we suggest that SMYD2 is a potential metastasis regulator and that the development of SMYD2-specific inhibitors may help to increase the efficacy of lung cancer treatment.", "classifications": [ { "id": "Hamamoto", "label": "Group Hamamoto", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Kwangho", "last_name": "Kim", "name": null }, { "creator_type": "author", "first_name": "Tae Young", "last_name": "Ryu", "name": null }, { "creator_type": "author", "first_name": "Eunsun", "last_name": "Jung", "name": null }, { "creator_type": "author", "first_name": "Tae-Su", "last_name": "Han", "name": null }, { "creator_type": "author", "first_name": "Jinkwon", "last_name": "Lee", "name": null }, { "creator_type": "author", "first_name": "Seon-Kyu", "last_name": "Kim", "name": null }, { "creator_type": "author", "first_name": "Yu Na", "last_name": "Roh", "name": null }, { "creator_type": "author", "first_name": "Moo-Seung", "last_name": "Lee", "name": null }, { "creator_type": "author", "first_name": "Cho-Rok", "last_name": "Jung", "name": null }, { "creator_type": "author", "first_name": "Jung Hwa", "last_name": "Lim", "name": null }, { "creator_type": "author", "first_name": "Ryuji", "last_name": "Hamamoto", "name": null }, { "creator_type": "author", "first_name": "Hye Won", "last_name": "Lee", "name": null }, { "creator_type": "author", "first_name": "Keun", "last_name": "Hur", "name": null }, { "creator_type": "author", "first_name": "Mi-Young", "last_name": "Son", "name": null }, { "creator_type": "author", "first_name": "Dae-Soo", "last_name": "Kim", "name": null }, { "creator_type": "author", "first_name": "Hyun-Soo", "last_name": "Cho", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s12276-023-00987-1" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "37121971" } }, "mesh": [ { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Cell Proliferation", "descriptor_ui": "D049109", "major_topic": false }, { "descriptor": "Epigenesis, Genetic", "descriptor_ui": "D044127", "major_topic": false }, { "descriptor": "Epithelial-Mesenchymal Transition", "descriptor_ui": "D058750", "major_topic": false }, { "descriptor": "Histone Methyltransferases", "descriptor_ui": "D000076983", "major_topic": false }, { "descriptor": "Histone-Lysine N-Methyltransferase", "descriptor_ui": "D011495", "major_topic": false }, { "descriptor": "Histones", "descriptor_ui": "D006657", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Lung Neoplasms", "descriptor_ui": "D008175", "major_topic": true }, { "descriptor": "Smad3 Protein", "descriptor_ui": "D051900", "major_topic": false } ], "publication": { "conference_name": null, "date": "2023 May 1", "date_precision": "day", "issue": "", "normalized_date": "2023-05-01", "pages": "", "proceedings_title": null, "publisher": "", "title": "Experimental & molecular medicine", "volume": "", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Epigenetic regulation of SMAD3 by histone methyltransferase SMYD2 promotes lung cancer metastasis.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Nano-DDS, a drug delivery system using nanoparticles, is a promising tool to reduce adverse drug reactions and maximize drug efficiency. Understanding the intracellular dynamics following the accumulation of nanoparticles in tissues, such as cellular uptake, distribution, metabolism, and pharmacological effects, is essential to maximize drug efficiency; however, it remains elusive. In this study, we tracked the intracellular behavior of nanoparticles of a prodrug, cholesterol-linked SN-38 (CLS), in a label-free manner using Raman and autofluorescence imaging. Bright autofluorescent spots were observed in cells treated with CLS nanoparticles, and the color tone of the bright spots changed with incubation time. The Raman spectra of the bright spots showed that the autofluorescence came from the nanoparticles taken into cells, and the change in color of bright spots indicated that CLS turned into SN-38 via hydrolysis inside a cell. It was found that most of the SN-38 were localized in small regions in the cytoplasm even after the conversion from CLS, and only a small amount of SN-38 was dissolved and migrated into other cytoplasm regions and the nucleus. The massive size growth of cells was observed within several tens of hours after the treatment with CLS nanoparticles. Moreover, Raman images of cells using the cytochrome c band and the fluorescence images of cells stained with JC-1 showed that cellular uptake of CLS nanoparticles efficiently caused mitochondrial damage. These results show that the combination of Raman and autofluorescence imaging can provide insight into the intracellular behavior of prodrug nanoparticles and the cell response and facilitate the development of nano-DDSs.", "classifications": [ { "id": "Nakabayashi", "label": "Group Nakabayashi", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Masato", "last_name": "Machida", "name": null }, { "creator_type": "author", "first_name": "Toshiki", "last_name": "Sugimura", "name": null }, { "creator_type": "author", "first_name": "Shinji", "last_name": "Kajimoto", "name": null }, { "creator_type": "author", "first_name": "Farsai", "last_name": "Taemaitree", "name": null }, { "creator_type": "author", "first_name": "Yoshitaka", "last_name": "Koseki", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Kasai", "name": null }, { "creator_type": "author", "first_name": "Takakazu", "last_name": "Nakabayashi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/acs.jpcb.3c01133" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "37094294" } }, "mesh": [ { "descriptor": "Drug Delivery Systems", "descriptor_ui": "D016503", "major_topic": false }, { "descriptor": "Irinotecan", "descriptor_ui": "D000077146", "major_topic": false }, { "descriptor": "Nanoparticles", "descriptor_ui": "D053758", "major_topic": true }, { "descriptor": "Optical Imaging", "descriptor_ui": "D061848", "major_topic": false }, { "descriptor": "Prodrugs", "descriptor_ui": "D011355", "major_topic": true }, { "descriptor": "Spectrum Analysis, Raman", "descriptor_ui": "D013059", "major_topic": false } ], "publication": { "conference_name": null, "date": "2023 Apr 24", "date_precision": "day", "issue": "", "normalized_date": "2023-04-24", "pages": "", "proceedings_title": null, "publisher": "", "title": "The journal of physical chemistry. B", "volume": "", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Label-Free Tracking of Nanoprodrug Cellular Uptake and Metabolism Using Raman and Autofluorescence Imaging.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Cytoplasmic stress granules (SGs) are phase-separated membrane-less organelles that form in response to various stress stimuli. SGs are mainly composed of non-canonical stalled 48S preinitiation complexes. In addition, many other proteins also accumulate into SGs, but the list is still incomplete. SG assembly suppresses apoptosis and promotes cell survival under stress. Furthermore, hyperformation of SGs is frequently observed in various human cancers and accelerates tumor development and progression by reducing stress-induced damage of cancer cells. Therefore, they are of clinical importance. However, the precise mechanism underlying SG-mediated inhibition of apoptosis remains ill-defined. Here, using a proximity-labeling proteomic approach, we comprehensively analyzed SG-resident proteins and identified the executioner caspases, caspase-3 and -7, as SG components. We demonstrate that accumulation of caspase-3/7 into SGs is mediated by evolutionarily conserved amino acid residues within their large catalytic domains and inhibits caspase activities and consequent apoptosis induced by various stresses. Expression of an SG-localization-deficient caspase-3 mutant in cells largely counteracted the anti-apoptotic effect of SGs, whereas enforced relocalization of the caspase-3 mutant to SGs restored it. Thus, SG-mediated sequestration of executioner caspases is a mechanism underlying the broad cytoprotective function of SGs. Furthermore, using a mouse xenograft tumor model, we show that this mechanism prevents cancer cells from apoptosis in tumor tissues, thereby promoting cancer progression. Our results reveal the functional crosstalk between SG-mediated cell survival and caspase-mediated cell death signaling pathways and delineate a molecular mechanism that dictates cell-fate decisions under stress and promotes tumorigenesis.", "classifications": [ { "id": "JPMJCR2022", "label": "JPMJCR2022", "researcher": "Mutsuhiro Takekawa", "type": "grant" }, { "id": "Takekawa", "label": "Group Takekawa", "parent": "Takekawa", "type": "group" }, { "id": "Takekawa", "label": "Team Takekawa", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Daichi", "last_name": "Fujikawa", "name": null }, { "creator_type": "author", "first_name": "Takanori", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Yoshioka", "name": null }, { "creator_type": "author", "first_name": "Zizheng", "last_name": "Li", "name": null }, { "creator_type": "author", "first_name": "Hisashi", "last_name": "Moriizumi", "name": null }, { "creator_type": "author", "first_name": "Mari", "last_name": "Taguchi", "name": null }, { "creator_type": "author", "first_name": "Noriko", "last_name": "Tokai-Nishizumi", "name": null }, { "creator_type": "author", "first_name": "Hiroko", "last_name": "Kozuka-Hata", "name": null }, { "creator_type": "author", "first_name": "Masaaki", "last_name": "Oyama", "name": null }, { "creator_type": "author", "first_name": "Mutsuhiro", "last_name": "Takekawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.cub.2023.04.012" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "37119817" } }, "mesh": [ { "descriptor": "Apoptosis", "descriptor_ui": "D017209", "major_topic": false }, { "descriptor": "Caspase 3", "descriptor_ui": "D053148", "major_topic": false }, { "descriptor": "Caspases", "descriptor_ui": "D020169", "major_topic": true }, { "descriptor": "Cytoplasmic Granules", "descriptor_ui": "D003594", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Proteomics", "descriptor_ui": "D040901", "major_topic": true }, { "descriptor": "Stress Granules", "descriptor_ui": "D000088162", "major_topic": false }, { "descriptor": "Stress, Physiological", "descriptor_ui": "D013312", "major_topic": false } ], "publication": { "conference_name": null, "date": "2023 Apr 21", "date_precision": "day", "issue": "", "normalized_date": "2023-04-21", "pages": "S0960-9822(23)00460-8", "proceedings_title": null, "publisher": "", "title": "Current biology : CB", "volume": "", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Stress granule formation inhibits stress-induced apoptosis by selectively sequestering executioner caspases.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The catalytic reaction system (CRS) formalism by Hordijk and Steel is a versatile method to model autocatalytic biochemical reaction networks. It is particularly suited, and has been widely used, to study self-sustainment and self-generation properties. Its distinguishing feature is the explicit assignment of a catalytic function to chemicals that are part of the system. In this work, it is shown that the subsequent and simultaneous catalytic functions give rise to an algebraic structure of a semigroup with the additional compatible operation of idempotent addition and a partial order. The aim of this article is to demonstrate that such semigroup models are a natural setup to describe and analyze self-sustaining CRS. The basic algebraic properties of the models are established and the notion of the function of any set of chemicals on the whole CRS is made precise. This leads to a natural discrete dynamical system on the power set of chemicals, which is obtained by iteratively considering the self-action on a set of chemicals by its own function. The fixed points of this dynamical system are proven to correspond to self-sustaining sets of chemicals, which are functionally closed. Finally, as the main application, a theorem on the maximal self-sustaining set and a structure theorem on the set of functionally closed self-sustaining sets of chemicals are proven.", "classifications": [ { "id": "JPMJCR1927", "label": "JPMJCR1927", "researcher": "Yuichi Wakamoto", "type": "grant" }, { "id": "Wakamoto", "label": "Group Wakamoto", "parent": "Wakamoto", "type": "group" }, { "id": "Wakamoto", "label": "Team Wakamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Dimitri", "last_name": "Loutchko", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/s00285-023-01898-5" }, "pmcid": { "normalized": "PMC10115742" }, "pmid": { "normalized": "37076601" } }, "mesh": [ { "descriptor": "Catalysis", "descriptor_ui": "D002384", "major_topic": true } ], "publication": { "conference_name": null, "date": "2023 Apr 19", "date_precision": "day", "issue": "5", "normalized_date": "2023-04-19", "pages": "78", "proceedings_title": null, "publisher": "", "title": "Journal of mathematical biology", "volume": "86", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Semigroup models for biochemical reaction networks.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Liquid-liquid phase separation is a phenomenon that features the formation of liquid droplets containing concentrated solutes. The droplets of neurodegeneration-associated proteins are prone to generate aggregates and cause diseases. To uncover the aggregation process from the droplets, it is necessary to analyze the protein structure with keeping the droplet state in a label-free manner, but there was no suitable method. In this study, we observed the structural changes of ataxin-3, a protein associated with Machado-Joseph disease, inside the droplets, using autofluorescence lifetime microscopy. Each droplet showed autofluorescence due to tryptophan (Trp) residues, and its lifetime increased with time, reflecting structural changes toward aggregation. We used Trp mutants to reveal the structural changes around each Trp and showed that the structural change consists of several steps on different timescales. We demonstrated that the present method visualizes the protein dynamics inside a droplet in a label-free manner. Further investigations revealed that the aggregate structure formed in the droplets differs from that formed in dispersed solutions and that a polyglutamine repeat extension in ataxin-3 hardly modulates the aggregation dynamics in the droplets. These findings highlight that the droplet environment facilitates unique protein dynamics different from those in solutions.", "classifications": [ { "id": "Nakabayashi", "label": "Group Nakabayashi", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Uchu", "last_name": "Matsuura", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Tahara", "name": null }, { "creator_type": "author", "first_name": "Shinji", "last_name": "Kajimoto", "name": null }, { "creator_type": "author", "first_name": "Takakazu", "last_name": "Nakabayashi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41598-023-33268-y" }, "pmcid": { "normalized": "PMC10113985" }, "pmid": { "normalized": "37076520" } }, "mesh": [ { "descriptor": "Ataxin-3", "descriptor_ui": "D000067699", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Machado-Joseph Disease", "descriptor_ui": "D017827", "major_topic": true } ], "publication": { "conference_name": null, "date": "2023 Apr 19", "date_precision": "day", "issue": "1", "normalized_date": "2023-04-19", "pages": "6389", "proceedings_title": null, "publisher": "", "title": "Scientific reports", "volume": "13", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Label-free autofluorescence lifetime reveals the structural dynamics of ataxin-3 inside droplets formed via liquid-liquid phase separation.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: Driver alterations may represent novel candidates for driver gene-guided therapy; however, intrahepatic cholangiocarcinoma (ICC) with multiple genomic aberrations makes them intractable. Therefore, the pathogenesis and metabolic changes of ICC need to be understood to develop new treatment strategies. We aimed to unravel the evolution of ICC and identify ICC-specific metabolic characteristics to investigate the metabolic pathway associated with ICC development using multiregional sampling to encompass the intra- and inter-tumoral heterogeneity. METHODS: We performed the genomic, transcriptomic, proteomic and metabolomic analysis of 39-77 ICC tumour samples and eleven normal samples. Further, we analysed their cell proliferation and viability. RESULTS: We demonstrated that intra-tumoral heterogeneity of ICCs with distinct driver genes per case exhibited neutral evolution, regardless of their tumour stage. Upregulation of BCAT1 and BCAT2 indicated the involvement of 'Val Leu Ile degradation pathway'. ICCs exhibit the accumulation of ubiquitous metabolites, such as branched-chain amino acids including valine, leucine, and isoleucine, to negatively affect cancer prognosis. We revealed that this metabolic pathway was almost ubiquitously altered in all cases with genomic diversity and might play important roles in tumour progression and overall survival. CONCLUSIONS: We propose a novel ICC onco-metabolic pathway that could enable the development of new therapeutic interventions.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Akihiro", "last_name": "Kitagawa", "name": null }, { "creator_type": "author", "first_name": "Tsuyoshi", "last_name": "Osawa", "name": null }, { "creator_type": "author", "first_name": "Miwa", "last_name": "Noda", "name": null }, { "creator_type": "author", "first_name": "Yuta", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Sho", "last_name": "Aki", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Nakano", "name": null }, { "creator_type": "author", "first_name": "Tomoko", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Dai", "last_name": "Shimizu", "name": null }, { "creator_type": "author", "first_name": "Hisateru", "last_name": "Komatsu", "name": null }, { "creator_type": "author", "first_name": "Maki", "last_name": "Sugaya", "name": null }, { "creator_type": "author", "first_name": "Junichi", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Keisuke", "last_name": "Kosai", "name": null }, { "creator_type": "author", "first_name": "Seiichiro", "last_name": "Takao", "name": null }, { "creator_type": "author", "first_name": "Yushi", "last_name": "Motomura", "name": null }, { "creator_type": "author", "first_name": "Kuniaki", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Qingjiang", "last_name": "Hu", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Fujii", "name": null }, { "creator_type": "author", "first_name": "Hiroaki", "last_name": "Wakiyama", "name": null }, { "creator_type": "author", "first_name": "Taro", "last_name": "Tobo", "name": null }, { "creator_type": "author", "first_name": "Hiroki", "last_name": "Uchida", "name": null }, { "creator_type": "author", "first_name": "Keishi", "last_name": "Sugimachi", "name": null }, { "creator_type": "author", "first_name": "Kohei", "last_name": "Shibata", "name": null }, { "creator_type": "author", "first_name": "Tohru", "last_name": "Utsunomiya", "name": null }, { "creator_type": "author", "first_name": "Shogo", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Hideshi", "last_name": "Ishii", "name": null }, { "creator_type": "author", "first_name": "Takanori", "last_name": "Hasegawa", "name": null }, { "creator_type": "author", "first_name": "Takaaki", "last_name": "Masuda", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Matsui", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Niida", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Yutaka", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Satoru", "last_name": "Miyano", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Aburatani", "name": null }, { "creator_type": "author", "first_name": "Yuichiro", "last_name": "Doki", "name": null }, { "creator_type": "author", "first_name": "Hidetoshi", "last_name": "Eguchi", "name": null }, { "creator_type": "author", "first_name": "Masaki", "last_name": "Mori", "name": null }, { "creator_type": "author", "first_name": "Keiichi I.", "last_name": "Nakayama", "name": null }, { "creator_type": "author", "first_name": "Teppei", "last_name": "Shimamura", "name": null }, { "creator_type": "author", "first_name": "Tatsuhiro", "last_name": "Shibata", "name": null }, { "creator_type": "author", "first_name": "Koshi", "last_name": "Mimori", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41416-023-02256-4" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "37076565" } }, "mesh": [ { "descriptor": "Amino Acids, Branched-Chain", "descriptor_ui": "D000597", "major_topic": false }, { "descriptor": "Bile Duct Neoplasms", "descriptor_ui": "D001650", "major_topic": true }, { "descriptor": "Bile Ducts, Intrahepatic", "descriptor_ui": "D001653", "major_topic": false }, { "descriptor": "Cholangiocarcinoma", "descriptor_ui": "D018281", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Proteomics", "descriptor_ui": "D040901", "major_topic": false }, { "descriptor": "Transaminases", "descriptor_ui": "D000637", "major_topic": false } ], "publication": { "conference_name": null, "date": "2023 Apr 19", "date_precision": "day", "issue": "", "normalized_date": "2023-04-19", "pages": "", "proceedings_title": null, "publisher": "", "title": "British journal of cancer", "volume": "", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Convergent genomic diversity and novel BCAA metabolism in intrahepatic cholangiocarcinoma.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The ability of a chemical reaction network to generate itself by catalyzed reactions from constantly present environmental food sources is considered a fundamental property in origin-of-life research. Based on Kaufmann's autocatalytic sets, Hordijk and Steel have constructed the versatile formalism of catalytic reaction systems (CRS) to model and to analyze such self-generating networks, which they named reflexively autocatalytic and food-generated. Recently, it was established that the subsequent and simultaenous catalytic functions of the chemicals of a CRS give rise to an algebraic structure, termed a semigroup model. The semigroup model allows to naturally consider the function of any subset of chemicals on the whole CRS. This gives rise to a generative dynamics by iteratively applying the function of a subset to the externally supplied food set. The fixed point of this dynamics yields the maximal self-generating set of chemicals. Moreover, the set of all functionally closed self-generating sets of chemicals is discussed and a structure theorem for this set is proven. It is also shown that a CRS which contains self-generating sets of chemicals cannot have a nilpotent semigroup model and thus a useful link to the combinatorial theory of finite semigroups is established. The main technical tool introduced and utilized in this work is the representation of the semigroup elements as decorated rooted trees, allowing to translate the generation of chemicals from a given set of resources into the semigroup language.", "classifications": [ { "id": "JPMJCR1927", "label": "JPMJCR1927", "researcher": "Yuichi Wakamoto", "type": "grant" }, { "id": "Wakamoto", "label": "Group Wakamoto", "parent": "Wakamoto", "type": "group" }, { "id": "Wakamoto", "label": "Team Wakamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Dimitri", "last_name": "Loutchko", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/s00285-023-01899-4" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "37071214" } }, "mesh": [ { "descriptor": "Catalysis", "descriptor_ui": "D002384", "major_topic": true } ], "publication": { "conference_name": null, "date": "2023 Apr 18", "date_precision": "day", "issue": "5", "normalized_date": "2023-04-18", "pages": "76", "proceedings_title": null, "publisher": "", "title": "Journal of mathematical biology", "volume": "86", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "An algebraic characterization of self-generating chemical reaction networks using semigroup models.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "High-throughput metabolomics has enabled the development of large-scale cohort studies. Long-term studies require multiple batch-based measurements, which require sophisticated quality control (QC) to eliminate unexpected bias to obtain biologically meaningful quantified metabolomic profiles. Liquid chromatography-mass spectrometry was used to analyze 10,833 samples in 279 batch measurements. The quantified profile included 147 lipids including acylcarnitine, fatty acids, glucosylceramide, lactosylceramide, lysophosphatidic acid, and progesterone. Each batch included 40 samples, and 5 QC samples were measured for 10 samples of each. The quantified data from the QC samples were used to normalize the quantified profiles of the sample data. The intra- and inter-batch median coefficients of variation (CV) among the 147 lipids were 44.3% and 20.8%, respectively. After normalization, the CV values decreased by 42.0% and 14.7%, respectively. The effect of this normalization on the subsequent analyses was also evaluated. The demonstrated analyses will contribute to obtaining unbiased, quantified data for large-scale metabolomics.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Akiyoshi", "last_name": "Hirayama", "name": null }, { "creator_type": "author", "first_name": "Takamasa", "last_name": "Ishikawa", "name": null }, { "creator_type": "author", "first_name": "Haruka", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Sanae", "last_name": "Yamanaka", "name": null }, { "creator_type": "author", "first_name": "Satsuki", "last_name": "Ikeda", "name": null }, { "creator_type": "author", "first_name": "Aya", "last_name": "Hirata", "name": null }, { "creator_type": "author", "first_name": "Sei", "last_name": "Harada", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Sugimoto", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Masaru", "last_name": "Tomita", "name": null }, { "creator_type": "author", "first_name": "Toru", "last_name": "Takebayashi", "name": null } ], "identifiers": { "doi": { "normalized": "10.3390/metabo13040558" }, "pmcid": { "normalized": "PMC10146188" }, "pmid": { "normalized": "37110217" } }, "mesh": [], "publication": { "conference_name": null, "date": "2023 Apr 13", "date_precision": "day", "issue": "4", "normalized_date": "2023-04-13", "pages": "", "proceedings_title": null, "publisher": "", "title": "Metabolites", "volume": "13", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Quality Control of Targeted Plasma Lipids in a Large-Scale Cohort Study Using Liquid Chromatography-Tandem Mass Spectrometry.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "TEAD transcription factors are responsible for the transcriptional output of Hippo signaling. TEAD activity is primarily regulated by phosphorylation of its coactivators, YAP and TAZ. In addition, cysteine palmitoylation has recently been shown to regulate TEAD activity. Here, we report lysine long-chain fatty acylation as a posttranslational modification of TEADs. Lysine fatty acylation occurs spontaneously via intramolecular transfer of acyl groups from the proximal acylated cysteine residue. Lysine fatty acylation, like cysteine palmitoylation, contributes to the transcriptional activity of TEADs by enhancing the interaction with YAP and TAZ, but it is more stable than cysteine acylation, suggesting that the lysine fatty-acylated TEAD acts as a \"stable active form.\" Significantly, lysine fatty acylation of TEAD increased upon Hippo signaling activation despite a decrease in cysteine acylation. Our results provide insight into the role of fatty-acyl modifications in the regulation of TEAD activity.", "classifications": [ { "id": "Sodeoka", "label": "Group Sodeoka", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Kota", "last_name": "Noritsugu", "name": null }, { "creator_type": "author", "first_name": "Takehiro", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Kosuke", "last_name": "Dodo", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Ohgane", "name": null }, { "creator_type": "author", "first_name": "Yasue", "last_name": "Ichikawa", "name": null }, { "creator_type": "author", "first_name": "Kota", "last_name": "Koike", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Morita", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Umehara", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Ogawa", "name": null }, { "creator_type": "author", "first_name": "Mikiko", "last_name": "Sodeoka", "name": null }, { "creator_type": "author", "first_name": "Naoshi", "last_name": "Dohmae", "name": null }, { "creator_type": "author", "first_name": "Minoru", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Akihiro", "last_name": "Ito", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.celrep.2023.112388" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "37060904" } }, "mesh": [ { "descriptor": "Acylation", "descriptor_ui": "D000215", "major_topic": false }, { "descriptor": "Cysteine", "descriptor_ui": "D003545", "major_topic": false }, { "descriptor": "Lysine", "descriptor_ui": "D008239", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "TEA Domain Transcription Factors", "descriptor_ui": "D000091262", "major_topic": true }, { "descriptor": "Transcription Factors", "descriptor_ui": "D014157", "major_topic": true } ], "publication": { "conference_name": null, "date": "2023 Apr 12", "date_precision": "day", "issue": "", "normalized_date": "2023-04-12", "pages": "112388", "proceedings_title": null, "publisher": "", "title": "Cell reports", "volume": "", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Lysine long-chain fatty acylation regulates the TEAD transcription factor.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Active microrheology was conducted in living cells by applying an optical-trapping force to vigorously fluctuating tracer beads with feedback-tracking technology. The complex shear modulus G(omega)=G(')(omega)-iG('')(omega) was measured in HeLa cells in an epithelial-like confluent monolayer. We found that G(omega) proportional, variant(-iomega)(1/2) over a wide range of frequencies (1 Hz < omega/2pi < 10 kHz). Actin disruption and cell-cycle progression from G1 to S and G2 phases only had a limited effect on G(omega) in living cells. On the other hand, G(omega) was found to be dependent on cell metabolism; ATP-depleted cells showed an increased elastic modulus G(')(omega) at low frequencies, giving rise to a constant plateau such that G(omega)=G(0)+A(-iomega)(1/2). Both the plateau and the additional frequency dependency proportional, variant(-iomega)(1/2) of ATP-depleted cells are consistent with a rheological response typical of colloidal jamming. On the other hand, the plateau G(0) disappeared in ordinary metabolically active cells, implying that living cells fluidize their internal states such that they approach the critical jamming point.", "classifications": [ { "id": "Miyamoto", "label": "Group Miyamoto", "parent": "Wakamoto", "type": "group" }, { "id": "Wakamoto", "label": "Team Wakamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Ebata", "name": null }, { "creator_type": "author", "first_name": "Katsuhiro", "last_name": "Umeda", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Nishizawa", "name": null }, { "creator_type": "author", "first_name": "Wataru", "last_name": "Nagao", "name": null }, { "creator_type": "author", "first_name": "Shono", "last_name": "Inokuchi", "name": null }, { "creator_type": "author", "first_name": "Yujiro", "last_name": "Sugino", "name": null }, { "creator_type": "author", "first_name": "Takafumi", "last_name": "Miyamoto", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Mizuno", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.bpj.2023.04.011" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "37050875" } }, "mesh": [ { "descriptor": "Actins", "descriptor_ui": "D000199", "major_topic": true }, { "descriptor": "Adenosine Triphosphate", "descriptor_ui": "D000255", "major_topic": true }, { "descriptor": "Elastic Modulus", "descriptor_ui": "D055119", "major_topic": false }, { "descriptor": "HeLa Cells", "descriptor_ui": "D006367", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Rheology", "descriptor_ui": "D012212", "major_topic": false } ], "publication": { "conference_name": null, "date": "2023 Apr 11", "date_precision": "day", "issue": "", "normalized_date": "2023-04-11", "pages": "S0006-3495(23)00241-2", "proceedings_title": null, "publisher": "", "title": "Biophysical journal", "volume": "", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Activity-dependent glassy cell mechanics Ⅰ: Mechanical properties measured with active microrheology.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "In eukaryotes, higher-order chromatin organization is spatiotemporally regulated as domains, for various cellular functions. However, their physical nature in living cells remains unclear (e.g., condensed domains or extended fiber loops; liquid-like or solid-like). Using novel approaches combining genomics, single-nucleosome imaging, and computational modeling, we investigated the physical organization and behavior of early DNA replicated regions in human cells, which correspond to Hi-C contact domains with active chromatin marks. Motion correlation analysis of two neighbor nucleosomes shows that nucleosomes form physically condensed domains with ~150-nm diameters, even in active chromatin regions. The mean-square displacement analysis between two neighbor nucleosomes demonstrates that nucleosomes behave like a liquid in the condensed domain on the ~150 nm/~0.5 s spatiotemporal scale, which facilitates chromatin accessibility. Beyond the micrometers/minutes scale, chromatin seems solid-like, which may contribute to maintaining genome integrity. Our study reveals the viscoelastic principle of the chromatin polymer; chromatin is locally dynamic and reactive but globally stable.", "classifications": [ { "id": "Onami", "label": "Group Onami", "parent": "Fujiwara", "type": "group" }, { "id": "Fujiwara", "label": "Team Fujiwara", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Tadasu", "last_name": "Nozaki", "name": null }, { "creator_type": "author", "first_name": "Soya", "last_name": "Shinkai", "name": null }, { "creator_type": "author", "first_name": "Satoru", "last_name": "Ide", "name": null }, { "creator_type": "author", "first_name": "Koichi", "last_name": "Higashi", "name": null }, { "creator_type": "author", "first_name": "Sachiko", "last_name": "Tamura", "name": null }, { "creator_type": "author", "first_name": "Masa A.", "last_name": "Shimazoe", "name": null }, { "creator_type": "author", "first_name": "Masaki", "last_name": "Nakagawa", "name": null }, { "creator_type": "author", "first_name": "Yutaka", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Okada", "name": null }, { "creator_type": "author", "first_name": "Masaki", "last_name": "Sasai", "name": null }, { "creator_type": "author", "first_name": "Shuichi", "last_name": "Onami", "name": null }, { "creator_type": "author", "first_name": "Ken", "last_name": "Kurokawa", "name": null }, { "creator_type": "author", "first_name": "Shiori", "last_name": "Iida", "name": null }, { "creator_type": "author", "first_name": "Kazuhiro", "last_name": "Maeshima", "name": null } ], "identifiers": { "doi": { "normalized": "10.1126/sciadv.adf1488" }, "pmcid": { "normalized": "PMC10075990" }, "pmid": { "normalized": "37018405" } }, "mesh": [ { "descriptor": "Chromatin", "descriptor_ui": "D002843", "major_topic": true }, { "descriptor": "Chromatin Assembly and Disassembly", "descriptor_ui": "D042002", "major_topic": false }, { "descriptor": "DNA", "descriptor_ui": "D004247", "major_topic": false }, { "descriptor": "Eukaryota", "descriptor_ui": "D056890", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Nucleosomes", "descriptor_ui": "D009707", "major_topic": true } ], "publication": { "conference_name": null, "date": "2023 Apr 5", "date_precision": "day", "issue": "14", "normalized_date": "2023-04-05", "pages": "eadf1488", "proceedings_title": null, "publisher": "", "title": "Science advances", "volume": "9", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Condensed but liquid-like domain organization of active chromatin regions in living human cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "A luminescent three-dimensional coordination polymer (CP) of [Cd(II)(pmd)Ag(I)(CN)(2)(2)] (1; pmd = pyrimidine) comprising two different coordination modes of Ag(+) ions was synthesised herein. 1 exhibited thermochromic luminescence, accompanied by positive thermal elongation of the Agcdots, three dots, centeredAg distance. Moreover, 1 showed a bright phosphorescence with the highest photoluminescence quantum yield (Phi(em)), approximately 60% at room temperature, among previously reported phosphorescent Ag-based CPs or metal-organic frameworks.", "classifications": [ { "id": "Hijikata", "label": "Group Hijikata", "parent": "Tsuchiya", "type": "group" }, { "id": "Tsuchiya", "label": "Team Tsuchiya", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Haruka", "last_name": "Yoshino", "name": null }, { "creator_type": "author", "first_name": "Masaki", "last_name": "Saigo", "name": null }, { "creator_type": "author", "first_name": "Kiyoshi", "last_name": "Miyata", "name": null }, { "creator_type": "author", "first_name": "Ken", "last_name": "Onda", "name": null }, { "creator_type": "author", "first_name": "Jenny", "last_name": "Pirillo", "name": null }, { "creator_type": "author", "first_name": "Yuh", "last_name": "Hijikata", "name": null }, { "creator_type": "author", "first_name": "Wataru", "last_name": "Kosaka", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Miyasaka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1039/d3cc00179b" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "36987740" } }, "mesh": [], "publication": { "conference_name": null, "date": "2023 Mar 29", "date_precision": "day", "issue": "", "normalized_date": "2023-03-29", "pages": "", "proceedings_title": null, "publisher": "", "title": "Chemical communications (Cambridge, England)", "volume": "", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Unprecedented highly efficient photoluminescence in a phosphorescent Ag(I) coordination polymer.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: Platinum etoposide plus anti-programmed cell death ligand-1 (PD-L1) antibody therapy is the standard of care for extensive-stage small cell lung cancer (ES-SCLC). However, patient characteristics associated with the efficacy of the combination therapy in SCLC are unclear. METHODS: We retrospectively reviewed post-surgical limited-stage (LS)-SCLC and ES-SCLC patients treated with atezolizumab plus carboplatin and etoposide (ACE). The association between SCLC subtypes based on transcriptomic data and pathological findings, including CD8-positive tumor-infiltrating lymphocyte (TIL) status, was investigated in the LS-SCLC cohort. The association between the efficacy of ACE therapy, pathological subtypes, and TIL status was evaluated in the ES-SCLC cohort. RESULTS: The LS-SCLC cohort (N = 48) was classified into four SCLC subtypes (ASCL1 + NEUROD1 [SCLC-A + N, N = 17], POU2F3 [SCLC-P, N = 15], YAP1 [SCLC-Y, N = 10], and inflamed [SCLC-I, N = 6]) based on transcriptomic data. SCLC-I showed enriched immune-related pathways, the highest immune score (CD8A expression and T-cell-inflamed gene expression profiles), and epithelial-mesenchymal transition (EMT), in transcriptional subtypes. Immunohistochemical staining (IHC) showed that SCLC-I had the highest density of CD8-positive TILs in transcriptional subtypes. In the ES-SCLC cohort, the efficacy of ACE therapy did not differ according to pathological subtypes. The progression-free survival (PFS) of TIL(High) patients was significantly longer than that of TIL(Low) patients (PFS: 7.3 months vs. 4.0 months, p < 0.001). CONCLUSION: Tumors with a high density of TILs, which represent the most immunogenic SCLC subtype (SCLC-I), based on transcriptomic data could benefit from ACE therapy.", "classifications": [ { "id": "Hamamoto", "label": "Group Hamamoto", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Masayuki", "last_name": "Shirasawa", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Kouya", "last_name": "Shiraishi", "name": null }, { "creator_type": "author", "first_name": "Ayako", "last_name": "Takigami", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Takayanagi", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Imabayashi", "name": null }, { "creator_type": "author", "first_name": "Yuji", "last_name": "Matsumoto", "name": null }, { "creator_type": "author", "first_name": "Ken", "last_name": "Masuda", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Shinno", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Okuma", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Goto", "name": null }, { "creator_type": "author", "first_name": "Hidehito", "last_name": "Horinouchi", "name": null }, { "creator_type": "author", "first_name": "Masaya", "last_name": "Yotsukura", "name": null }, { "creator_type": "author", "first_name": "Yukihiro", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Kazuo", "last_name": "Nakagawa", "name": null }, { "creator_type": "author", "first_name": "Takaaki", "last_name": "Tsuchida", "name": null }, { "creator_type": "author", "first_name": "Ryuji", "last_name": "Hamamoto", "name": null }, { "creator_type": "author", "first_name": "Noboru", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Noriko", "last_name": "Motoi", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Kohno", "name": null }, { "creator_type": "author", "first_name": "Shun-Ichi", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Yuichiro", "last_name": "Ohe", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.lungcan.2023.107183" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "37037178" } }, "mesh": [ { "descriptor": "Etoposide", "descriptor_ui": "D005047", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Lung Neoplasms", "descriptor_ui": "D008175", "major_topic": true }, { "descriptor": "Phenotype", "descriptor_ui": "D010641", "major_topic": false }, { "descriptor": "Retrospective Studies", "descriptor_ui": "D012189", "major_topic": false }, { "descriptor": "Small Cell Lung Carcinoma", "descriptor_ui": "D055752", "major_topic": true } ], "publication": { "conference_name": null, "date": "2023 Mar 25", "date_precision": "day", "issue": "", "normalized_date": "2023-03-25", "pages": "107183", "proceedings_title": null, "publisher": "", "title": "Lung cancer (Amsterdam, Netherlands)", "volume": "179", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Identification of inflamed-phenotype of small cell lung cancer leading to the efficacy of anti-PD-L1 antibody and chemotherapy.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The analysis of super-enhancers (SEs) has recently attracted attention in elucidating the molecular mechanisms of cancer and other diseases. SEs are genomic structures that strongly induce gene expression and have been reported to contribute to the overexpression of oncogenes. Because the analysis of SEs and integrated analysis with other data are performed using large amounts of genome-wide data, artificial intelligence technology, with machine learning at its core, has recently begun to be utilized. In promoting precision medicine, it is important to consider information from SEs in addition to genomic data; therefore, machine learning technology is expected to be introduced appropriately in terms of building a robust analysis platform with a high generalization performance. In this review, we explain the history and principles of SE, and the results of SE analysis using state-of-the-art machine learning and integrated analysis with other data are presented to provide a comprehensive understanding of the current status of SE analysis in the field of medical biology. Additionally, we compared the accuracy between existing machine learning methods on the benchmark dataset and attempted to explore the kind of data preprocessing and integration work needed to make the existing algorithms work on the benchmark dataset. Furthermore, we discuss the issues and future directions of current SE analysis.", "classifications": [ { "id": "Hamamoto", "label": "Group Hamamoto", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Ryuji", "last_name": "Hamamoto", "name": null }, { "creator_type": "author", "first_name": "Ken", "last_name": "Takasawa", "name": null }, { "creator_type": "author", "first_name": "Norio", "last_name": "Shinkai", "name": null }, { "creator_type": "author", "first_name": "Hidenori", "last_name": "Machino", "name": null }, { "creator_type": "author", "first_name": "Nobuji", "last_name": "Kouno", "name": null }, { "creator_type": "author", "first_name": "Ken", "last_name": "Asada", "name": null }, { "creator_type": "author", "first_name": "Masaaki", "last_name": "Komatsu", "name": null }, { "creator_type": "author", "first_name": "Syuzo", "last_name": "Kaneko", "name": null } ], "identifiers": { "doi": { "normalized": "10.1093/bib/bbad107" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "36960780" } }, "mesh": [ { "descriptor": "Algorithms", "descriptor_ui": "D000465", "major_topic": true }, { "descriptor": "Artificial Intelligence", "descriptor_ui": "D001185", "major_topic": true }, { "descriptor": "Enhancer Elements, Genetic", "descriptor_ui": "D004742", "major_topic": false }, { "descriptor": "Genomics", "descriptor_ui": "D023281", "major_topic": false }, { "descriptor": "Machine Learning", "descriptor_ui": "D000069550", "major_topic": false } ], "publication": { "conference_name": null, "date": "2023 Mar 23", "date_precision": "day", "issue": "", "normalized_date": "2023-03-23", "pages": "bbad107", "proceedings_title": null, "publisher": "", "title": "Briefings in bioinformatics", "volume": "", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Analysis of super-enhancer using machine learning and its application to medical biology.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Interactions between various molecular species in biological phenomena give rise to numerous networks. The investigation of these networks, including their statistical and biochemical interactions, supports a deeper understanding of biological phenomena. The clustering of nodes associated with molecular species and enrichment analysis is frequently applied to examine the biological significance of such network structures. However, these methods focus on delineating the function of a node. As such, in-depth investigations of the edges, which are the connections between the nodes, are rarely explored. In the current study, we aimed to investigate the functions of the edges rather than the nodes. To accomplish this, for each network, we categorized the edges and defined the edge type based on their biological annotations. Subsequently, we used the edge type to compare the network structures of the metabolome and transcriptome in the livers of healthy (wild-type) and obese (ob/ob) mice following oral glucose administration (OGTT). The findings demonstrate that the edge type can facilitate the characterization of the state of a network structure, thereby reducing the information available through datasets containing the OGTT response in the metabolome and transcriptome.", "classifications": [ { "id": "Kuroda", "label": "Group Kuroda", "parent": "Kuroda", "type": "group" }, { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yuki", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Shinsuke", "last_name": "Uda", "name": null }, { "creator_type": "author", "first_name": "Toshiya", "last_name": "Kokaji", "name": null }, { "creator_type": "author", "first_name": "Akiyoshi", "last_name": "Hirayama", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Yutaka", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Kuroda", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Kubota", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41598-023-31547-2" }, "pmcid": { "normalized": "PMC10036622" }, "pmid": { "normalized": "36959243" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Glucose", "descriptor_ui": "D005947", "major_topic": true }, { "descriptor": "Liver", "descriptor_ui": "D008099", "major_topic": false }, { "descriptor": "Metabolome", "descriptor_ui": "D055442", "major_topic": true }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Obese", "descriptor_ui": "D008820", "major_topic": false } ], "publication": { "conference_name": null, "date": "2023 Mar 23", "date_precision": "day", "issue": "1", "normalized_date": "2023-03-23", "pages": "4758", "proceedings_title": null, "publisher": "", "title": "Scientific reports", "volume": "13", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Comparison of hepatic responses to glucose perturbation between healthy and obese mice based on the edge type of network structures.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Tumor-associated macrophages (TAMs) contribute to tumor progression and chemoresistance; it is therefore important to clarify the altered functions of macrophages following chemotherapy. While extracellular heat shock protein (HSP) 70 is associated with therapeutic resistance, the effects of HSP70 on TAMs remain largely unknown. Here, we conducted in vitro experiments and immunohistochemistry in 116 breast carcinoma specimens to determine whether the secretion of HSP70 from breast cancer cells following chemotherapy affects macrophage function. It was revealed that the interaction of epirubicin (EPI)-exposed breast cancer cells with macrophages enhanced tumor progression, and EPI promoted the secretion of extracellular HSP70 from breast cancer cells. The expression of pro-tumorigenic macrophage marker CD163 was decreased in macrophages treated with a conditioned medium (CM) from HSP70-silenced breast cancer cells. Breast cancer cells treated with CM from HSP70-silenced breast cancer cells showed decreased expression of transforming growth factor (TGF)-β, and the pro-tumorigenic effects of macrophages were impaired when TGF-β signaling was inhibited. Immunohistochemistry demonstrated that HSP70 served as a poor prognostic factor in conjunction with macrophage infiltration. It was therefore concluded that extracellular HSP70 levels increased following chemotherapy and enhanced the pro-tumorigenic effects of TAMs, either directly or indirectly, by regulating TGF-β expression in breast cancer cells.", "classifications": [ { "id": "Suzuki", "label": "Group Suzuki", "parent": "Takekawa", "type": "group" }, { "id": "Takekawa", "label": "Team Takekawa", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Mio", "last_name": "Yamaguchi-Tanaka", "name": null }, { "creator_type": "author", "first_name": "Kiyoshi", "last_name": "Takagi", "name": null }, { "creator_type": "author", "first_name": "Yasuhiro", "last_name": "Miki", "name": null }, { "creator_type": "author", "first_name": "Ai", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Erina", "last_name": "Iwabuchi", "name": null }, { "creator_type": "author", "first_name": "Minoru", "last_name": "Miyashita", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Suzuki", "name": null } ], "identifiers": { "doi": { "normalized": "10.3390/cancers15061903" }, "pmcid": { "normalized": "PMC10047178" }, "pmid": { "normalized": "36980788" } }, "mesh": [], "publication": { "conference_name": null, "date": "2023 Mar 22", "date_precision": "day", "issue": "6", "normalized_date": "2023-03-22", "pages": "", "proceedings_title": null, "publisher": "", "title": "Cancers", "volume": "15", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "The Pro-Tumorigenic Role of Chemotherapy-Induced Extracellular HSP70 from Breast Cancer Cells via Intratumoral Macrophages.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "To deal with the broad spectrum of coronaviruses, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), that threaten human health, it is essential to not only drugs develop that target viral proteins but also consider drugs that target host proteins/cellular processes to protect them from being hijacked for viral infection and replication. To this end, it has been reported that autophagy is deeply involved in coronavirus infection. In this study, we used airway organoids to screen a chemical library of autophagic modulators to identify compounds that could potentially be used to fight against infections by a broad range of coronaviruses. Among the 80 autophagy-related compounds tested, cycloheximide and thapsigargin reduced SARS-CoV-2 infection efficiency in a dose-dependent manner. Cycloheximide treatment reduced the infection efficiency of not only six SARS-CoV-2 variants but also human coronavirus (HCoV)-229E and HCoV-OC43. Cycloheximide treatment also reversed viral infection-induced innate immune responses. However, even low-dose (1 μM) cycloheximide treatment altered the expression profile of ribosomal RNAs; thus, side effects such as inhibition of protein synthesis in host cells must be considered. These results suggest that cycloheximide has broad-spectrum anti-coronavirus activity in vitro and warrants further investigation.", "classifications": [ { "id": "Yamamoto", "label": "Group Yamamoto", "parent": "Toyoshima", "type": "group" }, { "id": "Toyoshima", "label": "Team Toyoshima", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Rina", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Tomokazu", "last_name": "Tamura", "name": null }, { "creator_type": "author", "first_name": "Yukio", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Ayaka", "last_name": "Sakamoto", "name": null }, { "creator_type": "author", "first_name": "Naoko", "last_name": "Yasuhara", "name": null }, { "creator_type": "author", "first_name": "Hayato", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Nakano", "name": null }, { "creator_type": "author", "first_name": "Hiromitsu", "last_name": "Fuse", "name": null }, { "creator_type": "author", "first_name": "Akira", "last_name": "Ohta", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Noda", "name": null }, { "creator_type": "author", "first_name": "Yasufumi", "last_name": "Matsumura", "name": null }, { "creator_type": "author", "first_name": "Miki", "last_name": "Nagao", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Takasuke", "last_name": "Fukuhara", "name": null }, { "creator_type": "author", "first_name": "Kazuo", "last_name": "Takayama", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/acs.molpharmaceut.3c00114" }, "pmcid": { "normalized": null }, "pmid": { "normalized": null } }, "mesh": [], "publication": { "conference_name": null, "date": "2023-03-22", "date_precision": "day", "issue": "", "normalized_date": "2023-03-22", "pages": "", "proceedings_title": null, "publisher": "American Chemical Society", "title": "Molecular Pharmaceutics", "volume": "", "year": 2023 }, "ssbd": { "database": [ "ssbd-database-000334" ], "repository": [ "ssbd-repos-000334" ] }, "title": "Evaluation of Broad Anti-Coronavirus Activity of Autophagy-Related Compounds Using Human Airway Organoids", "url": "https://doi.org/10.1021/acs.molpharmaceut.3c00114", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Vasculogenic mesenchymal tumor (VMT), a primitive mesenchymal neoplasm enriched by various-sized atypical vessels, is a new entity that develops in mediastinal germ cell tumors (GCTs) with yolk sac tumor (YST) components after chemotherapy. Notably, patients with VMT in the residual GCT have increased risk of developing sarcomas or hematopoietic malignancies. Here, we report a late-teenage male patient with residual teratoma and high-grade VMT after chemotherapy for a mediastinal mixed GCT, including YST. Whole-exome sequencing revealed biallelic inactivation of TP53 and extensive copy number alterations that suggested whole-genome doubling. The biopsy tissue of the mixed GCT before chemotherapy exhibited overlapping genetic alterations to those in the VMT. Immunohistochemical analyses of the VMT showed that the abnormal vessels were positive for cytokeratin, glypican 3, EZH2, and IMP3. The findings that VMT inherits the genetic alterations of pre-existing mixed GCT and exhibits a partly YST-like immunophenotype might contribute to its clinical aggressiveness.", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Hirotake", "last_name": "Fujii", "name": null }, { "creator_type": "author", "first_name": "Yosuke", "last_name": "Yamada", "name": null }, { "creator_type": "author", "first_name": "Kentaro", "last_name": "Yamamura", "name": null }, { "creator_type": "author", "first_name": "Yoshihiro", "last_name": "Ishida", "name": null }, { "creator_type": "author", "first_name": "Marina", "last_name": "Tsujimura", "name": null }, { "creator_type": "author", "first_name": "Kazuhisa", "last_name": "Matsumoto", "name": null }, { "creator_type": "author", "first_name": "Satona", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Date", "name": null }, { "creator_type": "author", "first_name": "Tadaaki", "last_name": "Nishikawa", "name": null }, { "creator_type": "author", "first_name": "Yukihiro", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Jumpei", "last_name": "Kashima", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null }, { "creator_type": "author", "first_name": "Seishi", "last_name": "Ogawa", "name": null }, { "creator_type": "author", "first_name": "Alexander", "last_name": "Marx", "name": null }, { "creator_type": "author", "first_name": "Thomas M.", "last_name": "Ulbright", "name": null }, { "creator_type": "author", "first_name": "Hironori", "last_name": "Haga", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/s00428-023-03529-2" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "36943470" } }, "mesh": [ { "descriptor": "Adolescent", "descriptor_ui": "D000293", "major_topic": false }, { "descriptor": "Endodermal Sinus Tumor", "descriptor_ui": "D018240", "major_topic": true }, { "descriptor": "Exome Sequencing", "descriptor_ui": "D000073359", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mediastinal Neoplasms", "descriptor_ui": "D008479", "major_topic": true }, { "descriptor": "Mediastinum", "descriptor_ui": "D008482", "major_topic": false }, { "descriptor": "Neoplasms, Germ Cell and Embryonal", "descriptor_ui": "D009373", "major_topic": true }, { "descriptor": "Teratoma", "descriptor_ui": "D013724", "major_topic": true }, { "descriptor": "Testicular Neoplasms", "descriptor_ui": "D013736", "major_topic": true } ], "publication": { "conference_name": null, "date": "2023 Mar 21", "date_precision": "day", "issue": "", "normalized_date": "2023-03-21", "pages": "", "proceedings_title": null, "publisher": "", "title": "Virchows Archiv : an international journal of pathology", "volume": "", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "A case of vasculogenic mesenchymal tumor in the mediastinum: whole-exome sequencing reveals origin from pre-existing germ cell tumor.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The alkyne tag, consisting of only two carbons, is widely used as a bioorthogonal functional group due to its compactness and nonpolar structure, and various probes consisting of lipids bearing an alkyne tag have been developed. Here, we designed and synthesized analogues of ganglioside GM3 bearing an alkyne tag in the fatty acid moiety and evaluated the effect of the alkyne tag on the biological activity. To eliminate the influence of other factors such as degradation of the glycan chain when evaluating biological activity in a cellular environment, we introduced the tag into sialidase-resistant (S)-CHF-linked GM3 analogues developed by our group. The designed analogues were efficiently synthesized by tuning the protecting group of the glucosylsphingosine acceptor. The growth-promoting effect of these analogues on Had-1 cells was dramatically altered depending upon the position of the alkyne tag.", "classifications": [ { "id": "Sodeoka", "label": "Group Sodeoka", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Eisuke", "last_name": "Ota", "name": null }, { "creator_type": "author", "first_name": "Daiki", "last_name": "Takeda", "name": null }, { "creator_type": "author", "first_name": "Kana", "last_name": "Oonuma", "name": null }, { "creator_type": "author", "first_name": "Marie", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Hiroaki", "last_name": "Matoba", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Yoritate", "name": null }, { "creator_type": "author", "first_name": "Mikiko", "last_name": "Sodeoka", "name": null }, { "creator_type": "author", "first_name": "Go", "last_name": "Hirai", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/s10719-023-10111-0" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "36939991" } }, "mesh": [ { "descriptor": "G(M3) Ganglioside", "descriptor_ui": "D005679", "major_topic": true } ], "publication": { "conference_name": null, "date": "2023 Mar 20", "date_precision": "day", "issue": "", "normalized_date": "2023-03-20", "pages": "", "proceedings_title": null, "publisher": "", "title": "Glycoconjugate journal", "volume": "", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Synthesis and biological activity of ganglioside GM3 analogues with a (S)-CHF-Sialoside linkage and an alkyne tag.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Polarization of the zygote defines the body axis during plant development. In Arabidopsis (Arabidopsis thaliana), the zygote becomes polarized and elongates in the longitudinal direction, ultimately forming the apical-basal axis of the mature plant. Despite its importance, the mechanism for this elongation remains poorly understood. Based on live-cell imaging of the zygote, we developed new image analysis methods, referred to as coordinate normalization, that appropriately fix and align positions in an image, preventing fluctuation across a temporal sequence of images. Using these methods, we discovered that the zygote elongates only at its apical tip region, similar to tip-growing cells such as pollen tubes and root hairs. We also investigated the spatiotemporal dynamics of the apical tip contour of the zygote and observed that the zygote tip retains its isotropic, hemispherical apical shape during cell elongation. By looking at the elliptical fitting of the contour over time, we further discovered that the apical cell tip becomes thinner at first and then thickens, with a transient increase in growth speed that is followed by the first cell division. We performed the same series of analyses using root hairs and established that the hemispherical tip shape and the changes in growth rate associated with changes in tip size are both specific to the zygote. In summary, the Arabidopsis zygote undergoes directional elongation as a tip-growing cell, but its tip retains an unusual isotropic shape, and the manner of growth changes with the developmental stage.", "classifications": [ { "id": "JPMJCR2121", "label": "JPMJCR2121", "researcher": "Minako Ueda", "type": "grant" }, { "id": "Tsugawa", "label": "Group Tsugawa", "parent": "Ueda", "type": "group" }, { "id": "Ueda", "label": "Group Ueda", "parent": "Ueda", "type": "group" }, { "id": "Ueda", "label": "Team Ueda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Zichen", "last_name": "Kang", "name": null }, { "creator_type": "author", "first_name": "Hikari", "last_name": "Matsumoto", "name": null }, { "creator_type": "author", "first_name": "Tomonobu", "last_name": "Nonoyama", "name": null }, { "creator_type": "author", "first_name": "Sakumi", "last_name": "Nakagawa", "name": null }, { "creator_type": "author", "first_name": "Yukitaka", "last_name": "Ishimoto", "name": null }, { "creator_type": "author", "first_name": "Satoru", "last_name": "Tsugawa", "name": null }, { "creator_type": "author", "first_name": "Minako", "last_name": "Ueda", "name": null } ], "identifiers": { "doi": { "normalized": "10.1093/pcp/pcad020" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "36943754" } }, "mesh": [ { "descriptor": "Arabidopsis", "descriptor_ui": "D017360", "major_topic": true }, { "descriptor": "Arabidopsis Proteins", "descriptor_ui": "D029681", "major_topic": true }, { "descriptor": "Cell Division", "descriptor_ui": "D002455", "major_topic": false }, { "descriptor": "Plant Roots", "descriptor_ui": "D018517", "major_topic": false }, { "descriptor": "Pollen Tube", "descriptor_ui": "D053205", "major_topic": false }, { "descriptor": "Zygote", "descriptor_ui": "D015053", "major_topic": false } ], "publication": { "conference_name": null, "date": "2023 Mar 20", "date_precision": "day", "issue": "", "normalized_date": "2023-03-20", "pages": "pcad020", "proceedings_title": null, "publisher": "", "title": "Plant & cell physiology", "volume": "", "year": 2023 }, "ssbd": { "database": [ "ssbd-database-000323" ], "repository": [ "ssbd-repos-000323" ] }, "title": "Coordinate Normalization of Live-Cell Imaging Data Reveals Growth Dynamics of the Arabidopsis Zygote.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Small extracellular vesicles (sEV) contain various microRNAs (miRNAs) and play crucial roles in the tumor metastatic process. Although miR-29b levels in peritoneal exosomes was markedly reduced in patients with peritoneal metastases (PM), their role has not been fully clarified. In this study, we asked if the replacement of miR-29b can affect the development of PM in murine model. UE6E7T-12, a human bone marrow derived mesenchymal stem cells (BMSCs), were transfected with miR-29b-integrating recombinant lenti-viral vector and sEV isolated from culture supernatants using ultracentrifugation. The sEV contained markedly increased amounts of miR-29b compared with negative controls. Treatment with TGF-beta1 decreased the expression of E-cadherin and calretinin with increased expression of vimentin and fibronectin on human peritoneal mesothelial cells (HPMCs). However, the effects were totally abrogated by the adding miR-29b-rich sEV. The sEV inhibited proliferation and migration of HPMCs by 15% (p< 0.005, n=6), 70% (p< 0.005, n=6), and inhibited adhesion of NUGC-4 and MKN45 to HPMCs by 90 % (p< 0.0001, n=5) and 77% (p< 0.0001, n=5), respectively. MiR-29b-rich murine sEV were similarly obtained using mouse BMSCs and examined for in vivo effects with a syngeneic murine model using YTN16P, a highly metastatic clone of gastric cancer cell. Intraperitoneal (IP) transfer of the sEV for every 3 days markedly reduced the number of PM from YTN16P in the mesentery (p< 0.05, n=6) and the omentum (p< 0.05, n=6). BMSC-derived sEV are a useful carrier for IP administration of miR-29b which can suppress the development of PM of gastric cancer.", "classifications": [ { "id": "Kuchimaru", "label": "Group Kuchimaru", "parent": "Shintaku", "type": "group" }, { "id": "Shintaku", "label": "Team Shintaku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yuki", "last_name": "Kimura", "name": null }, { "creator_type": "author", "first_name": "Hideyuki", "last_name": "Ohzawa", "name": null }, { "creator_type": "author", "first_name": "Hideyo", "last_name": "Miyato", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Kaneko", "name": null }, { "creator_type": "author", "first_name": "Takahiro", "last_name": "Kuchimaru", "name": null }, { "creator_type": "author", "first_name": "Rei", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Hironori", "last_name": "Yamaguchi", "name": null }, { "creator_type": "author", "first_name": "Kentaro", "last_name": "Kurashina", "name": null }, { "creator_type": "author", "first_name": "Shin", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Yoshinori", "last_name": "Hosoya", "name": null }, { "creator_type": "author", "first_name": "Alan Kawarai", "last_name": "Lefor", "name": null }, { "creator_type": "author", "first_name": "Naohiro", "last_name": "Sata", "name": null }, { "creator_type": "author", "first_name": "Joji", "last_name": "Kitayama", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/cas.15793" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "36939028" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Disease Models, Animal", "descriptor_ui": "D004195", "major_topic": false }, { "descriptor": "Exosomes", "descriptor_ui": "D055354", "major_topic": true }, { "descriptor": "Extracellular Vesicles", "descriptor_ui": "D000067128", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "MicroRNAs", "descriptor_ui": "D035683", "major_topic": true }, { "descriptor": "Peritoneal Neoplasms", "descriptor_ui": "D010534", "major_topic": true }, { "descriptor": "Stomach Neoplasms", "descriptor_ui": "D013274", "major_topic": true } ], "publication": { "conference_name": null, "date": "2023 Mar 20", "date_precision": "day", "issue": "", "normalized_date": "2023-03-20", "pages": "", "proceedings_title": null, "publisher": "", "title": "Cancer science", "volume": "", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Intraperitoneal transfer of miR-29b-containing small extracellular vesicles can suppress peritoneal metastases of gastric cancer.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "We introduce a novel approach to determine the critical quality attributes (CQAs) of mesenchymal stem cells (MSCs) expected to exert immunosuppressive effects. MSCs retained homeostatic replication potentials, such as sustainable growth and consistent cell morphology as a population, in early passages, but lost them in late passages. Characteristic surface markers of MSCs (ie, CD73, CD90, and CD105) were no longer expressed at 2 weeks after subcutaneous transplantation into NOG mice when MSCs from late passages were transplanted, but not when MSCs from early passages were transplanted, suggesting that the biological effects of the MSCs differed according to the timing of cell harvesting and highlighting the importance of specifying MSCs that retained homeostatic features to define the CQAs. The homeostatic features of MSCs related to the balance of the redox system, nutrient requirements, and mitochondrial function were also observed until a certain passage. Therefore, we could define the CQAs of MSCs related to manufacturing by selecting process parameters (PPs) underlying the homeostatic features of MSCs and measuring these PPs quantitatively to specify the cell population with homeostatic features by limiting the passage number. The validity of the PPs stipulated in our pilot study was verified using an SKG murine arthritis model, and critical PPs (CPPs) were then selected among the PPs. Thus, CQAs related to manufacturing in the developmental phase could be defined by the CPPs in this manner, and the concept of CQAs could be refined continuously toward commercial manufacturing.", "classifications": [ { "id": "Suzuki", "label": "Group Suzuki", "parent": "Takekawa", "type": "group" }, { "id": "Takekawa", "label": "Team Takekawa", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Takako", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Mao", "last_name": "Arita", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Tamura", "name": null }, { "creator_type": "author", "first_name": "Miho", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Hirohito", "last_name": "Katayama", "name": null }, { "creator_type": "author", "first_name": "Hirotaka", "last_name": "Kuroda", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Shin", "last_name": "Kawamata", "name": null } ], "identifiers": { "doi": { "normalized": "10.1093/stcltm/szad005" }, "pmcid": { "normalized": "PMC10021496" }, "pmid": { "normalized": "36917628" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Cell Proliferation", "descriptor_ui": "D049109", "major_topic": false }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Mesenchymal Stem Cells", "descriptor_ui": "D059630", "major_topic": true }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Pilot Projects", "descriptor_ui": "D010865", "major_topic": false } ], "publication": { "conference_name": null, "date": "2023 Mar 17", "date_precision": "day", "issue": "3", "normalized_date": "2023-03-17", "pages": "169-182", "proceedings_title": null, "publisher": "", "title": "Stem cells translational medicine", "volume": "12", "year": 2023 }, "ssbd": { "database": [ "ssbd-database-000318" ], "repository": [ "ssbd-repos-000318" ] }, "title": "A Novel Approach for Determining the Critical Quality Attributes of Mesenchymal Stem Cells by Specifying Cell Population With Replication Potential.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Contractile force generated in actomyosin stress fibers (SFs) is transmitted along SFs to the extracellular matrix (ECM), which contributes to cell migration and sensing of ECM rigidity. In this study, we show that efficient force transmission along SFs relies on actin crosslinking by alpha-actinin. Upon reduction of alpha-actinin-mediated crosslinks, the myosin II activity induced flows of actin filaments and myosin II along SFs, leading to a decrease in traction force exertion to ECM. The fluidized SFs maintained their cable integrity probably through enhanced actin polymerization throughout SFs. A computational modeling analysis suggested that lowering the density of actin crosslinks caused viscous slippage of actin filaments in SFs and, thereby, dissipated myosin-generated force transmitting along SFs. As a cellular scale outcome, alpha-actinin depletion attenuated the ECM-rigidity-dependent difference in cell migration speed, which suggested that alpha-actinin-modulated SF mechanics is involved in the cellular response to ECM rigidity.", "classifications": [ { "id": "JPMJCR1921", "label": "JPMJCR1921", "researcher": "Itaru Imayoshi", "type": "grant" }, { "id": "Imayoshi", "label": "Group Imayoshi", "parent": "Imayoshi", "type": "group" }, { "id": "Okuda", "label": "Group Okuda", "parent": "Imayoshi", "type": "group" }, { "id": "Imayoshi", "label": "Team Imayoshi", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Hiroki", "last_name": "Katsuta", "name": null }, { "creator_type": "author", "first_name": "Satoru", "last_name": "Okuda", "name": null }, { "creator_type": "author", "first_name": "Kazuaki", "last_name": "Nagayama", "name": null }, { "creator_type": "author", "first_name": "Hiroaki", "last_name": "Machiyama", "name": null }, { "creator_type": "author", "first_name": "Satoru", "last_name": "Kidoaki", "name": null }, { "creator_type": "author", "first_name": "Masashi", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Sokabe", "name": null }, { "creator_type": "author", "first_name": "Takaki", "last_name": "Miyata", "name": null }, { "creator_type": "author", "first_name": "Hiroaki", "last_name": "Hirata", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.isci.2023.106090" }, "pmcid": { "normalized": "PMC9958379" }, "pmid": { "normalized": "36852278" } }, "mesh": [], "publication": { "conference_name": null, "date": "2023 Mar 17", "date_precision": "day", "issue": "3", "normalized_date": "2023-03-17", "pages": "106090", "proceedings_title": null, "publisher": "", "title": "iScience", "volume": "26", "year": 2023 }, "ssbd": { "database": [ "ssbd-database-000292" ], "repository": [ "ssbd-repos-000292" ] }, "title": "Actin crosslinking by alpha-actinin averts viscous dissipation of myosin force transmission in stress fibers.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Abstract Human in vitro oogenesis provides a framework for clarifying the mechanism of human oogenesis. To create its benchmark, it is vital to promote in vitro oogenesis using a model physiologically close to humans. Here, we establish a foundation for in vitro oogenesis in cynomolgus (cy) monkeys (Macaca fascicularis): cy female embryonic stem cells harboring one active and one inactive X chromosome (Xa and Xi, respectively) differentiate robustly into primordial germ cell-like cells, which in xenogeneic reconstituted ovaries develop efficiently into oogonia and, remarkably, further into meiotic oocytes at the zygotene stage. This differentiation entails comprehensive epigenetic reprogramming, including Xi reprogramming, yet Xa and Xi remain epigenetically asymmetric with, as partly observed in vivo, incomplete Xi reactivation. In humans and monkeys, the Xi epigenome in pluripotent stem cells functions as an Xi-reprogramming determinant. We further show that developmental pathway over-activations with suboptimal up-regulation of relevant meiotic genes impede in vitro meiotic progression. Cy in vitro oogenesis exhibits critical homology with the human system, including with respect to bottlenecks, providing a salient model for advancing human in vitro oogenesis.", "classifications": [ { "id": "Yamamoto", "label": "Group Yamamoto", "parent": "Toyoshima", "type": "group" }, { "id": "Toyoshima", "label": "Team Toyoshima", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Sayuri", "last_name": "Gyobu-Motani", "name": null }, { "creator_type": "author", "first_name": "Yukihiro", "last_name": "Yabuta", "name": null }, { "creator_type": "author", "first_name": "Ken", "last_name": "Mizuta", "name": null }, { "creator_type": "author", "first_name": "Yoshitaka", "last_name": "Katou", "name": null }, { "creator_type": "author", "first_name": "Ikuhiro", "last_name": "Okamoto", "name": null }, { "creator_type": "author", "first_name": "Masanori", "last_name": "Kawasaki", "name": null }, { "creator_type": "author", "first_name": "Ayaka", "last_name": "Kitamura", "name": null }, { "creator_type": "author", "first_name": "Tomoyuki", "last_name": "Tsukiyama", "name": null }, { "creator_type": "author", "first_name": "Chizuru", "last_name": "Iwatani", "name": null }, { "creator_type": "author", "first_name": "Hideaki", "last_name": "Tsuchiya", "name": null }, { "creator_type": "author", "first_name": "Taro", "last_name": "Tsujimura", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Tomonori", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Mitinori", "last_name": "Saitou", "name": null } ], "identifiers": { "doi": { "normalized": "10.15252/embj.2022112962" }, "pmcid": { "normalized": null }, "pmid": { "normalized": null } }, "mesh": [], "publication": { "conference_name": null, "date": "2023-03-16", "date_precision": "day", "issue": "n/a", "normalized_date": "2023-03-16", "pages": "e112962", "proceedings_title": null, "publisher": "John Wiley & Sons, Ltd", "title": "The EMBO Journal", "volume": "n/a", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Induction of fetal meiotic oocytes from embryonic stem cells in cynomolgus monkeys", "url": "https://www.embopress.org/doi/full/10.15252/embj.2022112962", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Tissue specimen quality assurance is a major issue of precision medicine for rare cancers. However, the laboratory standards and quality of pathological specimens prepared in Asian hospitals remain unknown. To understand the methods in Southeast Asian oncology hospitals and to clarify how pre-analytics affect the quality of formalin-fixed paraffin-embedded (FFPE) specimens, a questionnaire surveying pre-analytical procedures (Part I), quality assessment of immunohistochemistry staining (IHC) and DNA/RNA extracted from the representative FFPE specimen from each hospital (Part II), and quality of DNA/RNA extracted from FFPE of rare cancer patients for genomic sequencing (Part III), were conducted. Quality measurements for DNA/RNA included DeltaDeltaCt, DV200, and cDNA yield. Six major cancer hospitals from Malaysia, Philippines, and Vietnam participated. One hospital showed unacceptable quality for the DNA/RNA assessment, but improved by revising laboratory procedures. Only 57% (n=73) of the 128 rare cancer patients' specimens met both DNA and RNA quality criteria for Next-Generation Sequencing. Median DV200 was 80.7% and 64.3% for qualified and failed RNA, respectively. Median DeltaDeltaCt was 1.25 for qualified and 4.89 for failed DNA. Longer storage period was significantly associated with poor DNA (fail:qualify = 1579:321 days, p<0.001) and RNA (fail:qualify = 1070:280 days, p<0.001). After improvement of pre-analytical factors, the qualification rate increased for hospitals A and E from 41.5% to 70.5% and 62.5% to 86%, respectively. This is the first report to elucidate the pre-analytical laboratory procedures of main Southeast Asian oncology hospitals. An external quality assessment program may improve factors associated with tumor FFPE specimen quality.", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Hitomi Sumiyoshi", "last_name": "Okuma", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Yoshihisa", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Motoko", "last_name": "Arakaki", "name": null }, { "creator_type": "author", "first_name": "Chiharu", "last_name": "Mizoguchi", "name": null }, { "creator_type": "author", "first_name": "Lina", "last_name": "Inagaki", "name": null }, { "creator_type": "author", "first_name": "Voon", "last_name": "Pei Jye", "name": null }, { "creator_type": "author", "first_name": "Adam", "last_name": "Malik Bin Ismail", "name": null }, { "creator_type": "author", "first_name": "Hwoei", "last_name": "Fen Soo Hoo", "name": null }, { "creator_type": "author", "first_name": "Suhana", "last_name": "Yusak", "name": null }, { "creator_type": "author", "first_name": "Marcelo", "last_name": "Severino B Imasa", "name": null }, { "creator_type": "author", "first_name": "Thinh", "last_name": "Nguyen Huy", "name": null }, { "creator_type": "author", "first_name": "Tu", "last_name": "Thai Anh", "name": null }, { "creator_type": "author", "first_name": "Shinji", "last_name": "Kohsaka", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Mano", "name": null }, { "creator_type": "author", "first_name": "Kan", "last_name": "Yonemori", "name": null }, { "creator_type": "author", "first_name": "Kenichi", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/cas.15790" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "36919757" } }, "mesh": [ { "descriptor": "Asia", "descriptor_ui": "D001208", "major_topic": false }, { "descriptor": "Asia, Southeastern", "descriptor_ui": "D001210", "major_topic": false }, { "descriptor": "DNA", "descriptor_ui": "D004247", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Neoplasms", "descriptor_ui": "D009369", "major_topic": true }, { "descriptor": "Paraffin Embedding", "descriptor_ui": "D016612", "major_topic": false }, { "descriptor": "Pathology, Molecular", "descriptor_ui": "D057089", "major_topic": true }, { "descriptor": "Quality Control", "descriptor_ui": "D011786", "major_topic": false }, { "descriptor": "RNA", "descriptor_ui": "D012313", "major_topic": false }, { "descriptor": "Tissue Fixation", "descriptor_ui": "D016707", "major_topic": false } ], "publication": { "conference_name": null, "date": "2023 Mar 15", "date_precision": "day", "issue": "", "normalized_date": "2023-03-15", "pages": "", "proceedings_title": null, "publisher": "", "title": "Cancer science", "volume": "", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Molecular pathology quality control in Southeast Asia: Results of a Multiregional Quality Assurance Study from MASTER KEY Asia.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The testis is an immune-privileged organ. It is considered that the testis somatic microenvironment is responsible for immune suppression. However, immunological properties of spermatogonial stem cells (SSCs) have remained unknown. Here, we report the birth of allogeneic offspring by enhanced expression of immunosuppressive PD-L1 in SSCs. In vitro supplementation of GDNF and FGF2 increased expression of PD-L1 in SSCs. Cultured SSCs maintained allogeneic spermatogenesis that persisted for >1 year. However, depletion or gene editing of Pd-l1 family genes in SSCs prevented allogeneic spermatogenesis, which suggested that germ cells are responsible for suppression of the allogeneic response. PD-L1 was induced by activation of the MAPK14-BCL6B pathway, which drives self-renewal by reactive oxygen species (ROS) generation. By contrast, reduced ROS or Mapk14 deficiency downregulated PD-L1. Allogeneic offspring were born after SSC transplantation into congenitally infertile and chemically castrated mice. Thus, SSCs have unique immunological properties, which make allogeneic recipients into \"surrogate fathers.\"", "classifications": [ { "id": "Yamamoto", "label": "Group Yamamoto", "parent": "Toyoshima", "type": "group" }, { "id": "Toyoshima", "label": "Team Toyoshima", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Takashi", "last_name": "Shinohara", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Hiroko", "last_name": "Morimoto", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Shiromoto", "name": null }, { "creator_type": "author", "first_name": "Mito", "last_name": "Kanatsu-Shinohara", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.stemcr.2023.02.008" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "36963391" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "B7-H1 Antigen", "descriptor_ui": "D060890", "major_topic": false }, { "descriptor": "Cell Proliferation", "descriptor_ui": "D049109", "major_topic": false }, { "descriptor": "Hematopoietic Stem Cell Transplantation", "descriptor_ui": "D018380", "major_topic": true }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mitogen-Activated Protein Kinase 14", "descriptor_ui": "D048308", "major_topic": true }, { "descriptor": "Reactive Oxygen Species", "descriptor_ui": "D017382", "major_topic": false }, { "descriptor": "Spermatogenesis", "descriptor_ui": "D013091", "major_topic": false }, { "descriptor": "Spermatogonia", "descriptor_ui": "D013093", "major_topic": false }, { "descriptor": "Testis", "descriptor_ui": "D013737", "major_topic": false } ], "publication": { "conference_name": null, "date": "2023 Mar 14", "date_precision": "day", "issue": "", "normalized_date": "2023-03-14", "pages": "S2213-6711(23)00055-3", "proceedings_title": null, "publisher": "", "title": "Stem cell reports", "volume": "", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Allogeneic offspring produced by induction of PD-L1 in spermatogonial stem cells via self-renewal stimulation.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Maternal factors present in oocytes and surrounding granulosa cells influence early development of embryos. In this study, we searched for epigenetic regulators that are expressed in oocytes and/or granulosa cells. Some of the 120 epigenetic regulators examined were expressed specifically in oocytes and/or granulosa cells. When their expression was examined in young versus aged oocytes or granulosa cells, many were significantly up- or downregulated in aged cells. The maternal role of six genes in development was investigated by generating oocyte-specific knock-out (MKO) mice. Two genes (Mllt10, Kdm2b) did not show maternal effects on later development, whereas maternal effects were evident for Kdm6a, Kdm4a, Prdm3, and Prdm16 for MKO female mice. Offspring from Kdm6a MKO mice underwent perinatal lethality at a higher rate. Pups derived from Prdm3;Prdm16 double MKO showed a higher incidence of postnatal death. Finally, embryos derived from Kdm4a MKO mice showed early developmental defects as early as the peri-implantation stage. These results suggest that many of maternal epigenetic regulators undergo differential expression upon aging. Some, such as Kdm4a, Kdm6a, Prdm3, and Prdm16, have maternal role in later embryonic or postnatal development. This article is protected by copyright. All rights reserved.", "classifications": [ { "id": "Nikaido", "label": "Group Nikaido", "parent": "Fujiwara", "type": "group" }, { "id": "Fujiwara", "label": "Team Fujiwara", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Hiromi", "last_name": "Nishimura", "name": null }, { "creator_type": "author", "first_name": "Yayoi", "last_name": "Ikawa", "name": null }, { "creator_type": "author", "first_name": "Eriko", "last_name": "Kajikawa", "name": null }, { "creator_type": "author", "first_name": "Natsumi", "last_name": "Shimizu-Mizuno", "name": null }, { "creator_type": "author", "first_name": "Sylvain", "last_name": "Hiver", "name": null }, { "creator_type": "author", "first_name": "Namine", "last_name": "Tabata-Okamoto", "name": null }, { "creator_type": "author", "first_name": "Masashi", "last_name": "Mori", "name": null }, { "creator_type": "author", "first_name": "Tomoya", "last_name": "Kitajima", "name": null }, { "creator_type": "author", "first_name": "Tetsutaro", "last_name": "Hayashi", "name": null }, { "creator_type": "author", "first_name": "Mika", "last_name": "Yoshimura", "name": null }, { "creator_type": "author", "first_name": "Mana", "last_name": "Umeda", "name": null }, { "creator_type": "author", "first_name": "Itoshi", "last_name": "Nikaido", "name": null }, { "creator_type": "author", "first_name": "Mineo", "last_name": "Kurokawa", "name": null }, { "creator_type": "author", "first_name": "Toshio", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Hamada", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/gtc.13024" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "36906847" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Embryonic Development", "descriptor_ui": "D047108", "major_topic": false }, { "descriptor": "Epigenesis, Genetic", "descriptor_ui": "D044127", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Histone Demethylases", "descriptor_ui": "D056466", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Oocytes", "descriptor_ui": "D009865", "major_topic": true }, { "descriptor": "Pregnancy", "descriptor_ui": "D011247", "major_topic": false }, { "descriptor": "Transcription Factors", "descriptor_ui": "D014157", "major_topic": true } ], "publication": { "conference_name": null, "date": "2023 Mar 12", "date_precision": "day", "issue": "", "normalized_date": "2023-03-12", "pages": "", "proceedings_title": null, "publisher": "", "title": "Genes to cells : devoted to molecular & cellular mechanisms", "volume": "", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Maternal epigenetic factors in embryonic and postnatal development.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "", "classifications": [ { "id": "Suzuki", "label": "Group Suzuki", "parent": "Takekawa", "type": "group" }, { "id": "Takekawa", "label": "Team Takekawa", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Toshiyuki", "last_name": "Itai", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Sugie", "name": null }, { "creator_type": "author", "first_name": "Yohei", "last_name": "Nitta", "name": null }, { "creator_type": "author", "first_name": "Ryuto", "last_name": "Maki", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Yoichi", "last_name": "Shinkai", "name": null }, { "creator_type": "author", "first_name": "Yoshihiro", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Nakano", "name": null }, { "creator_type": "author", "first_name": "Kazushi", "last_name": "Ichikawa", "name": null }, { "creator_type": "author", "first_name": "Nobuhiko", "last_name": "Okamoto", "name": null }, { "creator_type": "author", "first_name": "Yasuhiro", "last_name": "Utsuno", "name": null }, { "creator_type": "author", "first_name": "Eriko", "last_name": "Koshimizu", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Fujita", "name": null }, { "creator_type": "author", "first_name": "Kohei", "last_name": "Hamanaka", "name": null }, { "creator_type": "author", "first_name": "Yuri", "last_name": "Uchiyama", "name": null }, { "creator_type": "author", "first_name": "Naomi", "last_name": "Tsuchida", "name": null }, { "creator_type": "author", "first_name": "Noriko", "last_name": "Miyake", "name": null }, { "creator_type": "author", "first_name": "Kazuharu", "last_name": "Misawa", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Mizuguchi", "name": null }, { "creator_type": "author", "first_name": "Satoko", "last_name": "Miyatake", "name": null }, { "creator_type": "author", "first_name": "Naomichi", "last_name": "Matsumoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41598-023-30968-3" }, "pmcid": { "normalized": "PMC9998850" }, "pmid": { "normalized": "36894578" } }, "mesh": [], "publication": { "conference_name": null, "date": "2023 Mar 9", "date_precision": "day", "issue": "1", "normalized_date": "2023-03-09", "pages": "3954", "proceedings_title": null, "publisher": "", "title": "Scientific reports", "volume": "13", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Publisher Correction: A novel NONO variant that causes developmental delay and cardiac phenotypes.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "", "classifications": [ { "id": "Nishikii", "label": "Group Nishikii", "parent": "Shintaku", "type": "group" }, { "id": "Shintaku", "label": "Team Shintaku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yusuke", "last_name": "Kiyoki", "name": null }, { "creator_type": "author", "first_name": "Takayasu", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Sakura", "last_name": "Kito", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Matsuzaka", "name": null }, { "creator_type": "author", "first_name": "Shin", "last_name": "Morioka", "name": null }, { "creator_type": "author", "first_name": "Junko", "last_name": "Sasaki", "name": null }, { "creator_type": "author", "first_name": "Kenichi", "last_name": "Makishima", "name": null }, { "creator_type": "author", "first_name": "Tatsuhiro", "last_name": "Sakamoto", "name": null }, { "creator_type": "author", "first_name": "Hidekazu", "last_name": "Nishikii", "name": null }, { "creator_type": "author", "first_name": "Naoshi", "last_name": "Obara", "name": null }, { "creator_type": "author", "first_name": "Mamiko", "last_name": "Sakata-Yanagimoto", "name": null }, { "creator_type": "author", "first_name": "Takehiko", "last_name": "Sasaki", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Shimano", "name": null }, { "creator_type": "author", "first_name": "Shigeru", "last_name": "Chiba", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41375-023-01842-y" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "36890291" } }, "mesh": [ { "descriptor": "Fatty Acid Elongases", "descriptor_ui": "D000081031", "major_topic": false }, { "descriptor": "Fatty Acids", "descriptor_ui": "D005227", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Leukemia", "descriptor_ui": "D007938", "major_topic": true } ], "publication": { "conference_name": null, "date": "2023 Mar 8", "date_precision": "day", "issue": "", "normalized_date": "2023-03-08", "pages": "", "proceedings_title": null, "publisher": "", "title": "Leukemia", "volume": "", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "The fatty acid elongase Elovl6 is crucial for hematopoietic stem cell engraftment and leukemia propagation.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Oncometabolites, such as D/L-2-hydroxyglutarate (2HG), have directly been implicated in carcinogenesis; however, the underlying molecular mechanisms remain poorly understood. Here, we showed that the levels of the L-enantiomer of 2HG (L2HG) were specifically increased in colorectal cancer (CRC) tissues and cell lines compared with the D-enantiomer of 2HG (D2HG). In addition, L2HG increased the expression of ATF4 and its target genes by activating the mTOR pathway, which subsequently provided amino acids and improved the survival of CRC cells under serum deprivation. Downregulating the expression of L-2-hydroxyglutarate dehydrogenase (L2HGDH) and oxoglutarate dehydrogenase (OGDH) increased L2HG levels in CRC, thereby activating mTOR-ATF4 signaling. Furthermore, L2HGDH overexpression reduced L2HG-mediated mTOR-ATF4 signaling under hypoxia, whereas L2HGDH knockdown promoted tumor growth and amino acid metabolism in vivo. Together, these results indicate that L2HG ameliorates nutritional stress by activating the mTOR-ATF4 axis and thus could be a potential therapeutic target for CRC.", "classifications": [ { "id": "JPMJCR2123", "label": "JPMJCR2123", "researcher": "Shinya Kuroda", "type": "grant" }, { "id": "Kuroda", "label": "Group Kuroda", "parent": "Kuroda", "type": "group" }, { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Sho", "last_name": "Tabata", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Kojima", "name": null }, { "creator_type": "author", "first_name": "Takeharu", "last_name": "Sakamoto", "name": null }, { "creator_type": "author", "first_name": "Kaori", "last_name": "Igarashi", "name": null }, { "creator_type": "author", "first_name": "Ko", "last_name": "Umetsu", "name": null }, { "creator_type": "author", "first_name": "Takamasa", "last_name": "Ishikawa", "name": null }, { "creator_type": "author", "first_name": "Akiyoshi", "last_name": "Hirayama", "name": null }, { "creator_type": "author", "first_name": "Rie", "last_name": "Kajino-Sakamoto", "name": null }, { "creator_type": "author", "first_name": "Naoya", "last_name": "Sakamoto", "name": null }, { "creator_type": "author", "first_name": "Ken-Ichi", "last_name": "Yasumoto", "name": null }, { "creator_type": "author", "first_name": "Keiichi", "last_name": "Okano", "name": null }, { "creator_type": "author", "first_name": "Yasuyuki", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Shinichi", "last_name": "Yachida", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Aoki", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41388-023-02632-7" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "36879117" } }, "mesh": [ { "descriptor": "Activating Transcription Factor 4", "descriptor_ui": "D051701", "major_topic": false }, { "descriptor": "Alcohol Oxidoreductases", "descriptor_ui": "D000429", "major_topic": false }, { "descriptor": "Amino Acids", "descriptor_ui": "D000596", "major_topic": false }, { "descriptor": "Colorectal Neoplasms", "descriptor_ui": "D015179", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "TOR Serine-Threonine Kinases", "descriptor_ui": "D058570", "major_topic": true } ], "publication": { "conference_name": null, "date": "2023 Mar 6", "date_precision": "day", "issue": "", "normalized_date": "2023-03-06", "pages": "", "proceedings_title": null, "publisher": "", "title": "Oncogene", "volume": "", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "L-2hydroxyglutaric acid rewires amino acid metabolism in colorectal cancer via the mTOR-ATF4 axis.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Anal squamous cell carcinoma (ASCC) is a rare tumor of the gastrointestinal tract. We aimed to compare the genetic backgrounds and their effect on clinical outcomes between Japanese and Caucasian patients with ASCC. Forty-one patients diagnosed with ASCC at the National Cancer Center Hospital were enrolled and evaluated for clinicopathological features, human papillomavirus (HPV) infection, HPV genotypes, p16 expression, PD-L1, and association of p16 status with the efficacy of concurrent chemoradiotherapy (CCRT). Target sequencing for hotspot mutations in 50 cancer-related genes was performed using genomic DNA from 30 available samples. Of 41 patients, 34 were HPV-positive (among them, HPV 16 was predominant; 73.2%); 38 patients were p16-positive (92.7%); and 39 patients received CCRT, of whom 36 were p16-positive and three p16-negative. p16-positive patients showed better complete response than p16-negative patients. Among 28 samples, 15 showed mutations in PIK3CA, FBXW7, ABL1, TP53, and PTEN; no difference in mutation profiles between the Japanese and Caucasian cohorts was observed. Actionable mutations were detected in both Japanese and Caucasian patients with ASCC. Genetic backgrounds, such as the HPV 16 genotype and PIK3CA mutations, were common regardless of ethnicity. p16 status may be a prognostic biomarker for CCRT in Japanese patients with ASCC.", "classifications": [ { "id": "Hamamoto", "label": "Group Hamamoto", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Takahiko", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Takayanagi", "name": null }, { "creator_type": "author", "first_name": "Shigeki", "last_name": "Sekine", "name": null }, { "creator_type": "author", "first_name": "Taiki", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Yoko", "last_name": "Shimada", "name": null }, { "creator_type": "author", "first_name": "Maiko", "last_name": "Matsuda", "name": null }, { "creator_type": "author", "first_name": "Masayoshi", "last_name": "Yamada", "name": null }, { "creator_type": "author", "first_name": "Ryuji", "last_name": "Hamamoto", "name": null }, { "creator_type": "author", "first_name": "Tomoyasu", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Dai", "last_name": "Shida", "name": null }, { "creator_type": "author", "first_name": "Yukihide", "last_name": "Kanemitsu", "name": null }, { "creator_type": "author", "first_name": "Narikazu", "last_name": "Boku", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Kohno", "name": null }, { "creator_type": "author", "first_name": "Atsuo", "last_name": "Takashima", "name": null }, { "creator_type": "author", "first_name": "Kouya", "last_name": "Shiraishi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41598-023-30624-w" }, "pmcid": { "normalized": "PMC9984524" }, "pmid": { "normalized": "36869079" } }, "mesh": [ { "descriptor": "Anus Neoplasms", "descriptor_ui": "D001005", "major_topic": true }, { "descriptor": "Carcinoma, Squamous Cell", "descriptor_ui": "D002294", "major_topic": true }, { "descriptor": "East Asian People", "descriptor_ui": "D000095225", "major_topic": false }, { "descriptor": "Genes, Regulator", "descriptor_ui": "D005809", "major_topic": false }, { "descriptor": "Genomics", "descriptor_ui": "D023281", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Papillomavirus Infections", "descriptor_ui": "D030361", "major_topic": true }, { "descriptor": "White People", "descriptor_ui": "D044465", "major_topic": false } ], "publication": { "conference_name": null, "date": "2023 Mar 3", "date_precision": "day", "issue": "1", "normalized_date": "2023-03-03", "pages": "3587", "proceedings_title": null, "publisher": "", "title": "Scientific reports", "volume": "13", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Comparison of clinicopathological and genomic profiles in anal squamous cell carcinoma between Japanese and Caucasian cohorts.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Hypothalamic neurons regulate body homeostasis by sensing and integrating changes in the levels of key hormones and primary nutrients (amino acids, glucose, and lipids). However, the molecular mechanisms that enable hypothalamic neurons to detect primary nutrients remain elusive. Here, we identified L-type amino acid transporter 1 (LAT1) in hypothalamic leptin receptor (LepR)-expressing neurons as being important for systemic energy and bone homeostasis. We observed LAT1-dependent amino acid uptake in the hypothalamus, which was compromised in a mouse model of obesity and diabetes. Mice lacking LAT1 (encoded by Slc7a5) in LepR-expressing neurons exhibited obesity-related phenotypes and higher bone mass. Slc7a5 deficiency caused sympathetic dysfunction and leptin insensitivity in LepR-expressing neurons before obesity onset. Importantly, restoring Slc7a5 expression selectively in LepR-expressing ventromedial hypothalamus neurons rescued energy and bone homeostasis in mice deficient for Slc7a5 in LepR-expressing cells. Mechanistic target of rapamycin complex-1 (mTORC1) was found to be a crucial mediator of LAT1-dependent regulation of energy and bone homeostasis. These results suggest that the LAT1-mTORC1 axis in LepR-expressing neurons controls energy and bone homeostasis by fine-tuning sympathetic outflow, thus providing in vivo evidence of the implications of amino acid sensing by hypothalamic neurons in body homeostasis.", "classifications": [ { "id": "Inaba", "label": "Group Inaba", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Gyujin", "last_name": "Park", "name": null }, { "creator_type": "author", "first_name": "Kazuya", "last_name": "Fukasawa", "name": null }, { "creator_type": "author", "first_name": "Tetsuhiro", "last_name": "Horie", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Masuo", "name": null }, { "creator_type": "author", "first_name": "Yuka", "last_name": "Inaba", "name": null }, { "creator_type": "author", "first_name": "Takanori", "last_name": "Tatsuno", "name": null }, { "creator_type": "author", "first_name": "Takanori", "last_name": "Yamada", "name": null }, { "creator_type": "author", "first_name": "Kazuya", "last_name": "Tokumura", "name": null }, { "creator_type": "author", "first_name": "Sayuki", "last_name": "Iwahashi", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Iezaki", "name": null }, { "creator_type": "author", "first_name": "Katsuyuki", "last_name": "Kaneda", "name": null }, { "creator_type": "author", "first_name": "Yukio", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Yasuhito", "last_name": "Ishigaki", "name": null }, { "creator_type": "author", "first_name": "Michihiro", "last_name": "Mieda", "name": null }, { "creator_type": "author", "first_name": "Tomohiro", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Kazuma", "last_name": "Ogawa", "name": null }, { "creator_type": "author", "first_name": "Hiroki", "last_name": "Ochi", "name": null }, { "creator_type": "author", "first_name": "Shingo", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Yun-Bo", "last_name": "Shi", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Inoue", "name": null }, { "creator_type": "author", "first_name": "Hojoon", "last_name": "Lee", "name": null }, { "creator_type": "author", "first_name": "Eiichi", "last_name": "Hinoi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1172/jci.insight.154925" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "36862514" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Homeostasis", "descriptor_ui": "D006706", "major_topic": false }, { "descriptor": "Hypothalamus", "descriptor_ui": "D007031", "major_topic": true }, { "descriptor": "Large Neutral Amino Acid-Transporter 1", "descriptor_ui": "D027283", "major_topic": true }, { "descriptor": "Mechanistic Target of Rapamycin Complex 1", "descriptor_ui": "D000076222", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Obesity", "descriptor_ui": "D009765", "major_topic": false } ], "publication": { "conference_name": null, "date": "2023 Mar 2", "date_precision": "day", "issue": "", "normalized_date": "2023-03-02", "pages": "e154925", "proceedings_title": null, "publisher": "", "title": "JCI insight", "volume": "", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "L-type amino acid transporter 1 in hypothalamic neurons in mice maintains energy and bone homeostasis.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Raman microscopy is an emerging tool for molecular imaging and analysis of living samples. Use of Raman microscopy in life sciences is, however, still limited because of its slow measurement speed for spectral imaging and analysis. We developed a multiline-illumination Raman microscope to achieve ultrafast Raman spectral imaging. A spectrophotometer equipped with a periodic array of confocal slits detects Raman spectra from a sample irradiated by multiple line illuminations. A comb-like Raman hyperspectral image is formed on a two-dimensional detector in the spectrophotometer, and a hyperspectral Raman image is acquired by scanning the sample with multiline illumination array. By irradiating a sample with 21 simultaneous illumination lines, we achieved high-throughput Raman hyperspectral imaging of mouse brain tissue, acquiring 1108800 spectra in 11.4 min. We also measured mouse kidney and liver tissue as well as conducted label-free live-cell molecular imaging. The ultrafast Raman hyperspectral imaging enabled by the presented technique will expand the possible applications of Raman microscopy in biological and medical fields.", "classifications": [ { "id": "Fujita", "label": "Group Fujita", "parent": "Fujita", "type": "group" }, { "id": "Tanaka", "label": "Group Tanaka", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Kentaro", "last_name": "Mochizuki", "name": null }, { "creator_type": "author", "first_name": "Yasuaki", "last_name": "Kumamoto", "name": null }, { "creator_type": "author", "first_name": "Shunsuke", "last_name": "Maeda", "name": null }, { "creator_type": "author", "first_name": "Masato", "last_name": "Tanuma", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Kasai", "name": null }, { "creator_type": "author", "first_name": "Masashi", "last_name": "Takemura", "name": null }, { "creator_type": "author", "first_name": "Yoshinori", "last_name": "Harada", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Hideo", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Nicholas Isaac", "last_name": "Smith", "name": null }, { "creator_type": "author", "first_name": "Katsumasa", "last_name": "Fujita", "name": null } ], "identifiers": { "doi": { "normalized": "10.1364/boe.480611" }, "pmcid": { "normalized": "PMC10026569" }, "pmid": { "normalized": "36950233" } }, "mesh": [], "publication": { "conference_name": null, "date": "2023 Mar 1", "date_precision": "day", "issue": "3", "normalized_date": "2023-03-01", "pages": "1015-1026", "proceedings_title": null, "publisher": "", "title": "Biomedical optics express", "volume": "14", "year": 2023 }, "ssbd": { "database": [ "ssbd-database-000305" ], "repository": [ "ssbd-repos-000305" ] }, "title": "High-throughput line-illumination Raman microscopy with multislit detection.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The cortical motor cells (CMCs) in a legume pulvinus execute the reversible deformation in leaf movement that is driven by changes in turgor pressure. In contrast to the underlying osmotic regulation proper, the cell wall structure of CMCs that contributes to the movement has yet to be characterized in detail. Here, we report that the cell wall of CMCs has circumferential slits with low levels of cellulose deposition, which are widely conserved among legume species. This structure is unique and distinct from that of any other primary cell walls reported so far; thus, we named them \"pulvinar slits.\" Notably, we predominantly detected de-methyl-esterified homogalacturonan inside pulvinar slits, with a low deposition of highly methyl-esterified homogalacturonan, as with cellulose. In addition, Fourier-transform infrared spectroscopy analysis indicated that the cell wall composition of pulvini is different from that of other axial organs, such as petioles or stems. Moreover, monosaccharide analysis showed that pulvini are pectin-rich organs like developing stems and that the amount of galacturonic acid in pulvini is greater than in developing stems. Computer modeling suggested that pulvinar slits facilitate anisotropic extension in the direction perpendicular to the slits in the presence of turgor pressure. When tissue slices of CMCs were transferred to different extracellular osmotic conditions, pulvinar slits altered their opening width, indicating their deformability. In this study, we thus characterized a distinctive cell wall structure of CMCs, adding to knowledge of repetitive and reversible organ deformation as well as the structural diversity and function of the plant cell wall.", "classifications": [ { "id": "Tsugawa", "label": "Group Tsugawa", "parent": "Ueda", "type": "group" }, { "id": "Ueda", "label": "Team Ueda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Masahiro", "last_name": "Takahara", "name": null }, { "creator_type": "author", "first_name": "Satoru", "last_name": "Tsugawa", "name": null }, { "creator_type": "author", "first_name": "Shingo", "last_name": "Sakamoto", "name": null }, { "creator_type": "author", "first_name": "Taku", "last_name": "Demura", "name": null }, { "creator_type": "author", "first_name": "Miyuki T.", "last_name": "Nakata", "name": null } ], "identifiers": { "doi": { "normalized": "10.1093/plphys/kiad105" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "36849132" } }, "mesh": [ { "descriptor": "Cell Membrane", "descriptor_ui": "D002462", "major_topic": false }, { "descriptor": "Cell Wall", "descriptor_ui": "D002473", "major_topic": false }, { "descriptor": "Cellulose", "descriptor_ui": "D002482", "major_topic": false }, { "descriptor": "Fabaceae", "descriptor_ui": "D007887", "major_topic": true }, { "descriptor": "Pectins", "descriptor_ui": "D010368", "major_topic": false }, { "descriptor": "Pulvinar", "descriptor_ui": "D020649", "major_topic": true } ], "publication": { "conference_name": null, "date": "2023 Feb 28", "date_precision": "day", "issue": "", "normalized_date": "2023-02-28", "pages": "kiad105", "proceedings_title": null, "publisher": "", "title": "Plant physiology", "volume": "", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Pulvinar Slits: Cellulose-deficient and De-Methyl-Esterified Pectin-Rich Structures in a Legume Motor Cell.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Haematopoietic stem cells (HSCs) are a rare cell type that reconstitute the entire blood and immune systems after transplantation and can be used as a curative cell therapy for a variety of haematological diseases(1,2). However, the low number of HSCs in the body makes both biological analyses and clinical application difficult, and the limited extent to which human HSCs can be expanded ex vivo remains a substantial barrier to the wider and safer therapeutic use of HSC transplantation(3). Although various reagents have been tested in attempts to stimulate the expansion of human HSCs, cytokines have long been thought to be essential for supporting HSCs ex vivo(4). Here we report the establishment of a culture system that allows the long-term ex vivo expansion of human HSCs, achieved through the complete replacement of exogenous cytokines and albumin with chemical agonists and a caprolactam-based polymer. A phosphoinositide 3-kinase activator, in combination with a thrombopoietin-receptor agonist and the pyrimidoindole derivative UM171, were sufficient to stimulate the expansion of umbilical cord blood HSCs that are capable of serial engraftment in xenotransplantation assays. Ex vivo HSC expansion was further supported by split-clone transplantation assays and single-cell RNA-sequencing analysis. Our chemically defined expansion culture system will help to advance clinical HSC therapies.", "classifications": [ { "id": "Nishikii", "label": "Group Nishikii", "parent": "Shintaku", "type": "group" }, { "id": "Shintaku", "label": "Team Shintaku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Masatoshi", "last_name": "Sakurai", "name": null }, { "creator_type": "author", "first_name": "Kantaro", "last_name": "Ishitsuka", "name": null }, { "creator_type": "author", "first_name": "Ryoji", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Adam C.", "last_name": "Wilkinson", "name": null }, { "creator_type": "author", "first_name": "Takaharu", "last_name": "Kimura", "name": null }, { "creator_type": "author", "first_name": "Eiji", "last_name": "Mizutani", "name": null }, { "creator_type": "author", "first_name": "Hidekazu", "last_name": "Nishikii", "name": null }, { "creator_type": "author", "first_name": "Kazuhiro", "last_name": "Sudo", "name": null }, { "creator_type": "author", "first_name": "Hans Jiro", "last_name": "Becker", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Takemoto", "name": null }, { "creator_type": "author", "first_name": "Tsubasa", "last_name": "Sano", "name": null }, { "creator_type": "author", "first_name": "Keisuke", "last_name": "Kataoka", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Yukio", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "David G.", "last_name": "Kent", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Iwama", "name": null }, { "creator_type": "author", "first_name": "Shigeru", "last_name": "Chiba", "name": null }, { "creator_type": "author", "first_name": "Shinichiro", "last_name": "Okamoto", "name": null }, { "creator_type": "author", "first_name": "Hiromitsu", "last_name": "Nakauchi", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Yamazaki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41586-023-05739-9" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "36813966" } }, "mesh": [ { "descriptor": "Albumins", "descriptor_ui": "D000418", "major_topic": false }, { "descriptor": "Caprolactam", "descriptor_ui": "D002209", "major_topic": false }, { "descriptor": "Cell Culture Techniques", "descriptor_ui": "D018929", "major_topic": true }, { "descriptor": "Cell Proliferation", "descriptor_ui": "D049109", "major_topic": true }, { "descriptor": "Clone Cells", "descriptor_ui": "D002999", "major_topic": false }, { "descriptor": "Cytokines", "descriptor_ui": "D016207", "major_topic": true }, { "descriptor": "Fetal Blood", "descriptor_ui": "D005312", "major_topic": false }, { "descriptor": "Hematopoietic Stem Cell Transplantation", "descriptor_ui": "D018380", "major_topic": false }, { "descriptor": "Hematopoietic Stem Cells", "descriptor_ui": "D006412", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Indoles", "descriptor_ui": "D007211", "major_topic": false }, { "descriptor": "Phosphatidylinositol 3-Kinases", "descriptor_ui": "D019869", "major_topic": false }, { "descriptor": "Polymers", "descriptor_ui": "D011108", "major_topic": false }, { "descriptor": "Pyrimidines", "descriptor_ui": "D011743", "major_topic": false }, { "descriptor": "Receptors, Thrombopoietin", "descriptor_ui": "D053628", "major_topic": false }, { "descriptor": "Single-Cell Gene Expression Analysis", "descriptor_ui": "D000092386", "major_topic": false }, { "descriptor": "Transplantation, Heterologous", "descriptor_ui": "D014183", "major_topic": false } ], "publication": { "conference_name": null, "date": "2023 Feb 22", "date_precision": "day", "issue": "", "normalized_date": "2023-02-22", "pages": "", "proceedings_title": null, "publisher": "", "title": "Nature", "volume": "", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Chemically defined cytokine-free expansion of human haematopoietic stem cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Chiral Ni complexes have revolutionized both asymmetric acid-base and redox catalysis. However, the coordination isomerism of Ni complexes and their open-shell property still often hinder the elucidation of the origin of their observed stereoselectivity. Here, we report our experimental and computational investigations to clarify the mechanism of beta-nitrostyrene facial selectivity switching in Ni(II)-diamine-(OAc)(2)-catalyzed asymmetric Michael reactions. In the reaction with a dimethyl malonate, the Evans transition state (TS), in which the enolate binds in the same plane with the diamine ligand, is identified as the lowest-energy TS to promote C-C bond formation from the Si face in beta-nitrostyrene. In contrast, a detailed survey of the multiple potential pathways in the reaction with alpha-keto esters points to a clear preference for our proposed C-C bond-forming TS, in which the enolate coordinates to the Ni(II) center in apical-equatorial positions relative to the diamine ligand, thereby promoting Re face addition in beta-nitrostyrene. The N-H group plays a key orientational role in minimizing steric repulsion.", "classifications": [ { "id": "Sodeoka", "label": "Group Sodeoka", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yoshihiro", "last_name": "Sohtome", "name": null }, { "creator_type": "author", "first_name": "Shinsuke", "last_name": "Komagawa", "name": null }, { "creator_type": "author", "first_name": "Ayako", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Hashizume", "name": null }, { "creator_type": "author", "first_name": "Sylvain", "last_name": "Lectard", "name": null }, { "creator_type": "author", "first_name": "Mai", "last_name": "Akakabe", "name": null }, { "creator_type": "author", "first_name": "Yoshitaka", "last_name": "Hamashima", "name": null }, { "creator_type": "author", "first_name": "Masanobu", "last_name": "Uchiyama", "name": null }, { "creator_type": "author", "first_name": "Mikiko", "last_name": "Sodeoka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/acs.joc.2c02732" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "36813263" } }, "mesh": [ { "descriptor": "Acetates", "descriptor_ui": "D000085", "major_topic": false }, { "descriptor": "Carboxylic Acids", "descriptor_ui": "D002264", "major_topic": false }, { "descriptor": "Catalysis", "descriptor_ui": "D002384", "major_topic": false }, { "descriptor": "Diamines", "descriptor_ui": "D003959", "major_topic": true }, { "descriptor": "Ligands", "descriptor_ui": "D008024", "major_topic": false }, { "descriptor": "Nickel", "descriptor_ui": "D009532", "major_topic": true }, { "descriptor": "Organometallic Compounds", "descriptor_ui": "D009942", "major_topic": false }, { "descriptor": "Styrenes", "descriptor_ui": "D013343", "major_topic": false } ], "publication": { "conference_name": null, "date": "2023 Feb 22", "date_precision": "day", "issue": "", "normalized_date": "2023-02-22", "pages": "", "proceedings_title": null, "publisher": "", "title": "The Journal of organic chemistry", "volume": "", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Experimental and Computational Investigation of Facial Selectivity Switching in Nickel-Diamine-Acetate-Catalyzed Michael Reactions.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Insulin regulates various cellular metabolic processes by activating specific isoforms of the Akt family of kinases. Here, we elucidated metabolic pathways that are regulated in an Akt2-dependent manner. We constructed a transomics network by quantifying phosphorylated Akt substrates, metabolites, and transcripts in C2C12 skeletal muscle cells with acute, optogenetically induced activation of Akt2. We found that Akt2-specific activation predominantly affected Akt substrate phosphorylation and metabolite regulation rather than transcript regulation. The transomics network revealed that Akt2 regulated the lower glycolysis pathway and nucleotide metabolism and cooperated with Akt2-independent signaling to promote the rate-limiting steps in these processes, such as the first step of glycolysis, glucose uptake, and the activation of the pyrimidine metabolic enzyme CAD. Together, our findings reveal the mechanism of Akt2-dependent metabolic pathway regulation, paving the way for Akt2-targeting therapeutics in diabetes and metabolic disorders.", "classifications": [ { "id": "Kuroda", "label": "Group Kuroda", "parent": "Kuroda", "type": "group" }, { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Genki", "last_name": "Kawamura", "name": null }, { "creator_type": "author", "first_name": "Toshiya", "last_name": "Kokaji", "name": null }, { "creator_type": "author", "first_name": "Kentaro", "last_name": "Kawata", "name": null }, { "creator_type": "author", "first_name": "Yuka", "last_name": "Sekine", "name": null }, { "creator_type": "author", "first_name": "Yutaka", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Yoshibumi", "last_name": "Ueda", "name": null }, { "creator_type": "author", "first_name": "Mizuki", "last_name": "Endo", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Kuroda", "name": null }, { "creator_type": "author", "first_name": "Takeaki", "last_name": "Ozawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1126/scisignal.abn0782" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "36809024" } }, "mesh": [ { "descriptor": "Insulin", "descriptor_ui": "D007328", "major_topic": false }, { "descriptor": "Metabolic Networks and Pathways", "descriptor_ui": "D053858", "major_topic": false }, { "descriptor": "Muscle, Skeletal", "descriptor_ui": "D018482", "major_topic": false }, { "descriptor": "Optogenetics", "descriptor_ui": "D062308", "major_topic": true }, { "descriptor": "Phosphorylation", "descriptor_ui": "D010766", "major_topic": false }, { "descriptor": "Proto-Oncogene Proteins c-akt", "descriptor_ui": "D051057", "major_topic": true }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false } ], "publication": { "conference_name": null, "date": "2023 Feb 21", "date_precision": "day", "issue": "773", "normalized_date": "2023-02-21", "pages": "eabn0782", "proceedings_title": null, "publisher": "", "title": "Science signaling", "volume": "16", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Optogenetic decoding of Akt2-regulated metabolic signaling pathways in skeletal muscle cells using transomics analysis.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: Electroconvulsive therapy is effectively used for treatment-resistant depression; however, its neural mechanism is largely unknown. Resting-state functional magnetic resonance imaging is promising for monitoring outcomes of electroconvulsive therapy for depression. This study aimed to explore the imaging correlates of the electroconvulsive therapy effects on depression using Granger causality analysis and dynamic functional connectivity analyses. METHODS: We performed advanced analyses of resting-state functional magnetic resonance imaging data at the beginning and intermediate stages and end of the therapeutic course to identify neural markers that reflect or predict the therapeutic effects of electroconvulsive therapy on depression. RESULTS: We demonstrated that information flow between the functional networks analyzed by Granger causality changes during electroconvulsive therapy, and this change was correlated with the therapeutic outcome. Information flow and the dwell time (an index reflecting the temporal stability of functional connectivity) before electroconvulsive therapy are correlated with depressive symptoms during and after treatment. LIMITATIONS: First, the sample size was small. A larger group is needed to confirm our findings. Second, the influence of concomitant pharmacotherapy on our results was not fully addressed, although we expected it to be minimal because only minor changes in pharmacotherapy occurred during electroconvulsive therapy. Third, different scanners were used the groups, although the acquisition parameters were the same; a direct comparison between patient and healthy participant data was not possible. Thus, we presented the data of the healthy participants separately from that of the patients as a reference. CONCLUSIONS: These results show the specific properties of functional brain connectivity.", "classifications": [ { "id": "Fujiwara", "label": "Group Fujiwara", "parent": "Fujiwara", "type": "group" }, { "id": "Fujiwara", "label": "Team Fujiwara", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yusuke", "last_name": "Kyuragi", "name": null }, { "creator_type": "author", "first_name": "Naoya", "last_name": "Oishi", "name": null }, { "creator_type": "author", "first_name": "Shimpei", "last_name": "Yamasaki", "name": null }, { "creator_type": "author", "first_name": "Masaaki", "last_name": "Hazama", "name": null }, { "creator_type": "author", "first_name": "Jun", "last_name": "Miyata", "name": null }, { "creator_type": "author", "first_name": "Mami", "last_name": "Shibata", "name": null }, { "creator_type": "author", "first_name": "Hironobu", "last_name": "Fujiwara", "name": null }, { "creator_type": "author", "first_name": "Yasutaka", "last_name": "Fushimi", "name": null }, { "creator_type": "author", "first_name": "Toshiya", "last_name": "Murai", "name": null }, { "creator_type": "author", "first_name": "Taro", "last_name": "Suwa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.jad.2023.02.060" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "36801417" } }, "mesh": [ { "descriptor": "Brain", "descriptor_ui": "D001921", "major_topic": false }, { "descriptor": "Brain Mapping", "descriptor_ui": "D001931", "major_topic": false }, { "descriptor": "Depression", "descriptor_ui": "D003863", "major_topic": false }, { "descriptor": "Electroconvulsive Therapy", "descriptor_ui": "D004565", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Magnetic Resonance Imaging", "descriptor_ui": "D008279", "major_topic": false } ], "publication": { "conference_name": null, "date": "2023 Feb 18", "date_precision": "day", "issue": "", "normalized_date": "2023-02-18", "pages": "141-152", "proceedings_title": null, "publisher": "", "title": "Journal of affective disorders", "volume": "328", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Information flow and dynamic functional connectivity during electroconvulsive therapy in patients with depression.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Cancer cells coordinate the mTORC1 signals and the related metabolic pathways to robustly and rapidly grow in response to nutrient conditions. Although a CNC-family transcription factor NRF3 promotes cancer development, the biological relevance between NRF3 function and mTORC1 signals in cancer cells remains unknown. Hence, we showed that NRF3 contributes to cancer cell viability through mTORC1 activation in response to amino acids, particularly arginine. NRF3 induced SLC38A9 and RagC expression for the arginine-dependent mTORC1 recruitment onto lysosomes, and it also enhanced RAB5-mediated bulk macropinocytosis and SLC7A1-mediated selective transport for arginine loading into lysosomes. Besides, the inhibition of the NRF3-mTORC1 axis impaired mitochondrial function, leading to cancer cell apoptosis. Consistently, the aberrant upregulation of the axis caused tumor growth and poor prognosis. In conclusion, this study sheds light on the unique function of NRF3 in arginine-dependent mTORC1 activation and the pathophysiological aspects of the NRF3-mTORC1 axis in cancer development.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Shuuhei", "last_name": "Hirose", "name": null }, { "creator_type": "author", "first_name": "Tsuyoshi", "last_name": "Waku", "name": null }, { "creator_type": "author", "first_name": "Misato", "last_name": "Tani", "name": null }, { "creator_type": "author", "first_name": "Haruka", "last_name": "Masuda", "name": null }, { "creator_type": "author", "first_name": "Keiko", "last_name": "Endo", "name": null }, { "creator_type": "author", "first_name": "Sanae", "last_name": "Ashitani", "name": null }, { "creator_type": "author", "first_name": "Iori", "last_name": "Aketa", "name": null }, { "creator_type": "author", "first_name": "Hina", "last_name": "Kitano", "name": null }, { "creator_type": "author", "first_name": "Sota", "last_name": "Nakada", "name": null }, { "creator_type": "author", "first_name": "Ayaka", "last_name": "Wada", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Hatanaka", "name": null }, { "creator_type": "author", "first_name": "Tsuyoshi", "last_name": "Osawa", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Akira", "last_name": "Kobayashi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.isci.2023.106045" }, "pmcid": { "normalized": "PMC9932127" }, "pmid": { "normalized": "36818298" } }, "mesh": [], "publication": { "conference_name": null, "date": "2023 Feb 17", "date_precision": "day", "issue": "2", "normalized_date": "2023-02-17", "pages": "106045", "proceedings_title": null, "publisher": "", "title": "iScience", "volume": "26", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "NRF3 activates mTORC1 arginine-dependently for cancer cell viability.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "An essential challenge in diagnosing states of non-alcoholic fatty liver disease (NAFLD) is the early prediction of progression from non-alcoholic fatty liver (NAFL) to non-alcoholic steatohepatitis (NASH) before the disease progresses. Histological diagnoses of NAFLD rely on the appearance of anomalous tissue morphologies, and it is difficult to segment the biomolecular environment of the tissue through a conventional histopathological approach. Here, we show that hyper-spectral Raman imaging provides diagnostic information on NAFLD in rats, as spectral changes among disease states can be detected before histological characteristics emerge. Our results demonstrate that Raman imaging of NAFLD can be a useful tool for histopathologists, offering biomolecular distinctions among tissue states that cannot be observed through standard histopathological means.", "classifications": [ { "id": "Fujita", "label": "Group Fujita", "parent": "Fujita", "type": "group" }, { "id": "Tanaka", "label": "Group Tanaka", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Khalifa Mohammad", "last_name": "Helal", "name": null }, { "creator_type": "author", "first_name": "Harsono", "last_name": "Cahyadi", "name": null }, { "creator_type": "author", "first_name": "J. Nicholas", "last_name": "Taylor", "name": null }, { "creator_type": "author", "first_name": "Akira", "last_name": "Okajima", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Tabata", "name": null }, { "creator_type": "author", "first_name": "Yasuaki", "last_name": "Kumamoto", "name": null }, { "creator_type": "author", "first_name": "Kentaro", "last_name": "Mochizuki", "name": null }, { "creator_type": "author", "first_name": "Yoshito", "last_name": "Itoh", "name": null }, { "creator_type": "author", "first_name": "Tetsuro", "last_name": "Takamatsu", "name": null }, { "creator_type": "author", "first_name": "Hideo", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Katsumasa", "last_name": "Fujita", "name": null }, { "creator_type": "author", "first_name": "Tamiki", "last_name": "Komatsuzaki", "name": null }, { "creator_type": "author", "first_name": "Yoshinori", "last_name": "Harada", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/1873-3468.14600" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "36807196" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Liver", "descriptor_ui": "D008099", "major_topic": false }, { "descriptor": "Non-alcoholic Fatty Liver Disease", "descriptor_ui": "D065626", "major_topic": true }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false } ], "publication": { "conference_name": null, "date": "2023 Feb 17", "date_precision": "day", "issue": "", "normalized_date": "2023-02-17", "pages": "", "proceedings_title": null, "publisher": "", "title": "FEBS letters", "volume": "", "year": 2023 }, "ssbd": { "database": [], "repository": [ "ssbd-repos-000264" ] }, "title": "Raman imaging of rat non-alcoholic fatty liver tissues reveals distinct biomolecular states.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: We investigated the utility of a molecular classifier tool and genetic alterations for predicting prognosis in Japanese patients with endometrial cancer. METHODS: A total of 1029 patients with endometrial cancer from two independent cohorts were classified into four molecular subtype groups. The primary and secondary endpoints were relapse-free survival (RFS) and overall survival (OS), respectively. RESULTS: Among the 265 patients who underwent initial surgery, classified according to immunohistochemistry, patients with DNA polymerase epsilon exonuclease domain mutation had an excellent prognosis (RFS and OS), patients with no specific molecular profile (NSMP) and mismatch repair protein deficiency had an intermediate prognosis, and those with protein 53 abnormal expression (p53abn) had the worst prognosis (P < 0.001). In the NSMP group, mutant KRAS and wild-type ARID1A were associated with significantly poorer 5-year RFS (41.2%) than other genomic characteristics (P < 0.001). The distribution of the subtypes differed significantly between patients with recurrence/progression and classified by sequencing (n = 764) and patients who underwent initial surgery (P < 0.001). Among patients with recurrence/progression, 51.4% had the opportunity to receive molecular targeted therapy. CONCLUSIONS: A molecular classifier is a useful tool for determining prognosis and eligibility for molecularly targeted therapy in patients with endometrial cancer.", "classifications": [ { "id": "Hamamoto", "label": "Group Hamamoto", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yuka", "last_name": "Asami", "name": null }, { "creator_type": "author", "first_name": "Mayumi", "last_name": "Kobayashi Kato", "name": null }, { "creator_type": "author", "first_name": "Kengo", "last_name": "Hiranuma", "name": null }, { "creator_type": "author", "first_name": "Maiko", "last_name": "Matsuda", "name": null }, { "creator_type": "author", "first_name": "Yoko", "last_name": "Shimada", "name": null }, { "creator_type": "author", "first_name": "Mitsuya", "last_name": "Ishikawa", "name": null }, { "creator_type": "author", "first_name": "Takafumi", "last_name": "Koyama", "name": null }, { "creator_type": "author", "first_name": "Masaaki", "last_name": "Komatsu", "name": null }, { "creator_type": "author", "first_name": "Ryuji", "last_name": "Hamamoto", "name": null }, { "creator_type": "author", "first_name": "Minoru", "last_name": "Nagashima", "name": null }, { "creator_type": "author", "first_name": "Yasuhisa", "last_name": "Terao", "name": null }, { "creator_type": "author", "first_name": "Atsuo", "last_name": "Itakura", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Kohno", "name": null }, { "creator_type": "author", "first_name": "Akihiko", "last_name": "Sekizawa", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Matsumoto", "name": null }, { "creator_type": "author", "first_name": "Tomoyasu", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Kouya", "last_name": "Shiraishi", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Yoshida", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41416-023-02203-3" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "36797358" } }, "mesh": [ { "descriptor": "Biomarkers, Tumor", "descriptor_ui": "D014408", "major_topic": true }, { "descriptor": "Endometrial Neoplasms", "descriptor_ui": "D016889", "major_topic": true }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": false }, { "descriptor": "Neoplasm Recurrence, Local", "descriptor_ui": "D009364", "major_topic": false }, { "descriptor": "Prognosis", "descriptor_ui": "D011379", "major_topic": false } ], "publication": { "conference_name": null, "date": "2023 Feb 16", "date_precision": "day", "issue": "", "normalized_date": "2023-02-16", "pages": "", "proceedings_title": null, "publisher": "", "title": "British journal of cancer", "volume": "", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Utility of molecular subtypes and genetic alterations for evaluating clinical outcomes in 1029 patients with endometrial cancer.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Nonalcoholic steatohepatitis (NASH) is a disease that progresses from nonalcoholic fatty liver (NAFL) and which is characterized by inflammation and fibrosis. The purinergic P2Y(6) receptor (P2Y(6)R) is a pro-inflammatory G(q)/G(12) family protein-coupled receptor and reportedly contributes to intestinal inflammation and cardiovascular fibrosis, but its role in liver pathogenesis is unknown. Human genomics data analysis revealed that the liver P2Y(6)R mRNA expression level is increased during the progression from NAFL to NASH, which positively correlates with inductions of C-C motif chemokine 2 (CCL2) and collagen type I alpha1 chain (Col1a1) mRNAs. Therefore, we examined the impact of P2Y(6)R functional deficiency in mice crossed with a NASH model using a choline-deficient, L-amino acid-defined, high-fat diet (CDAHFD). Feeding CDAHFD for 6 weeks markedly increased P2Y(6)R expression level in mouse liver, which was positively correlated with CCL2 mRNA induction. Unexpectedly, the CDAHFD treatment for 6 weeks increased liver weights with severe steatosis in both wild-type (WT) and P2Y(6)R knockout (KO) mice, while the disease marker levels such as serum AST and liver CCL2 mRNA in CDAHFD-treated P2Y(6)R KO mice were rather aggravated compared with those of CDAHFD-treated WT mice. Thus, P2Y(6)R may not contribute to the progression of liver injury, despite increased expression in NASH liver.", "classifications": [ { "id": "JPMJCR2024", "label": "JPMJCR2024", "researcher": "Motohiro Nishida", "type": "grant" }, { "id": "Nishida", "label": "Group Nishida", "parent": "Nishida", "type": "group" }, { "id": "Nishimura", "label": "Group Nishimura", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Kazuhiro", "last_name": "Nishiyama", "name": null }, { "creator_type": "author", "first_name": "Kohei", "last_name": "Ariyoshi", "name": null }, { "creator_type": "author", "first_name": "Akiyuki", "last_name": "Nishimura", "name": null }, { "creator_type": "author", "first_name": "Yuri", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Xinya", "last_name": "Mi", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Kurose", "name": null }, { "creator_type": "author", "first_name": "Sang Geon", "last_name": "Kim", "name": null }, { "creator_type": "author", "first_name": "Motohiro", "last_name": "Nishida", "name": null } ], "identifiers": { "doi": { "normalized": "10.3390/ijms24043800" }, "pmcid": { "normalized": "PMC9963899" }, "pmid": { "normalized": "36835211" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Diet, High-Fat", "descriptor_ui": "D059305", "major_topic": false }, { "descriptor": "Disease Models, Animal", "descriptor_ui": "D004195", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Non-alcoholic Fatty Liver Disease", "descriptor_ui": "D065626", "major_topic": true }, { "descriptor": "Receptors, Purinergic P2", "descriptor_ui": "D018048", "major_topic": true }, { "descriptor": "RNA, Messenger", "descriptor_ui": "D012333", "major_topic": false } ], "publication": { "conference_name": null, "date": "2023 Feb 14", "date_precision": "day", "issue": "4", "normalized_date": "2023-02-14", "pages": "", "proceedings_title": null, "publisher": "", "title": "International journal of molecular sciences", "volume": "24", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Knockout of Purinergic P2Y(6) Receptor Fails to Improve Liver Injury and Inflammation in Non-Alcoholic Steatohepatitis.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Chiral pyrrolic macrocycles continue to attract interest. However, their molecular design remains challenging. Here, we report a calixpyrrole-based chiral macrocyclic system, calix[1]furan[1]pyrrole[1]thiophene (1), synthesized from an oligoketone. Macrocycle 1 adopts a partial cone conformation in the solid state, and undergoes racemization via ring inversion. Molecular dynamics simulations revealed that inversion of the thiophene is the rate determining step. Pyrrole N-methylation suppressed racemization and permitted chiral resolution. Enantioselective N-methylation also occurred in the presence of a chiral ammonium salt, although the stereoselectivity is modest. A unique feature of 1 is that it acts as a useful synthetic precursor to yield several calix[n]furan[n]pyrrole[n]thiophene products (n=2-4), including a calix[12]pyrrole analogue that to our knowledge constitutes the largest calix[n]pyrrole-like species to be structurally characterized.", "classifications": [ { "id": "Hijikata", "label": "Group Hijikata", "parent": "Tsuchiya", "type": "group" }, { "id": "Tsuchiya", "label": "Team Tsuchiya", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yuya", "last_name": "Inaba", "name": null }, { "creator_type": "author", "first_name": "Jian", "last_name": "Yang", "name": null }, { "creator_type": "author", "first_name": "Yu", "last_name": "Kakibayashi", "name": null }, { "creator_type": "author", "first_name": "Tomoki", "last_name": "Yoneda", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Ide", "name": null }, { "creator_type": "author", "first_name": "Yuh", "last_name": "Hijikata", "name": null }, { "creator_type": "author", "first_name": "Jenny", "last_name": "Pirillo", "name": null }, { "creator_type": "author", "first_name": "Ranajit", "last_name": "Saha", "name": null }, { "creator_type": "author", "first_name": "Jonathan L.", "last_name": "Sessler", "name": null }, { "creator_type": "author", "first_name": "Yasuhide", "last_name": "Inokuma", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/anie.202301460" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "36785520" } }, "mesh": [], "publication": { "conference_name": null, "date": "2023 Feb 13", "date_precision": "day", "issue": "", "normalized_date": "2023-02-13", "pages": "e202301460", "proceedings_title": null, "publisher": "", "title": "Angewandte Chemie (International ed. in English)", "volume": "", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Chiral Calix[3]pyrrole Derivatives: Synthesis, Racemization Kinetics, and Ring Expansion to Calix[9]- and Calix[12]pyrrole Analogues.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Insect galls are abnormal plant organs formed by gall-inducing insects to provide shelter and nutrients for themselves. Although insect galls are spatialized complex structures with unique shapes and functions, the molecular mechanism of the gall formation and the screening system for the gall inducing effectors remains unknown. Here, we demonstrate that an extract of a gall-inducing aphid, Schlechtendalia chinensis, induces an abnormal structure in the root-tip region of Arabidopsis seedlings. The abnormal structure is composed of stem-like cells, vascular, and protective tissues, as observed in typical insect galls. Furthermore, we confirm similarities in the gene expression profiles between the aphid-treated seedlings and the early developmental stages of Rhus javanica galls formed by S. chinensis. Based on the results, we propose a model system for analyzing the molecular mechanisms of gall formation: the Arabidopsis-based Gall-Forming Assay (Ab-GALFA). Ab-GALFA could be used not only as a model to elucidate the mechanisms underlying gall formation, but also as a bioassay system to isolate insect effector molecules of gall-induction.", "classifications": [ { "id": "Higaki", "label": "Group Higaki", "parent": "Ueda", "type": "group" }, { "id": "Ueda", "label": "Team Ueda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Tomoko", "last_name": "Hirano", "name": null }, { "creator_type": "author", "first_name": "Ayaka", "last_name": "Okamoto", "name": null }, { "creator_type": "author", "first_name": "Yoshihisa", "last_name": "Oda", "name": null }, { "creator_type": "author", "first_name": "Tomoaki", "last_name": "Sakamoto", "name": null }, { "creator_type": "author", "first_name": "Seiji", "last_name": "Takeda", "name": null }, { "creator_type": "author", "first_name": "Takakazu", "last_name": "Matsuura", "name": null }, { "creator_type": "author", "first_name": "Yoko", "last_name": "Ikeda", "name": null }, { "creator_type": "author", "first_name": "Takumi", "last_name": "Higaki", "name": null }, { "creator_type": "author", "first_name": "Seisuke", "last_name": "Kimura", "name": null }, { "creator_type": "author", "first_name": "Masa H.", "last_name": "Sato", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41598-023-29302-8" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "36781988" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Aphids", "descriptor_ui": "D001042", "major_topic": true }, { "descriptor": "Arabidopsis", "descriptor_ui": "D017360", "major_topic": true }, { "descriptor": "Insecta", "descriptor_ui": "D007313", "major_topic": false }, { "descriptor": "Plant Tumors", "descriptor_ui": "D010941", "major_topic": false }, { "descriptor": "Transcriptome", "descriptor_ui": "D059467", "major_topic": false } ], "publication": { "conference_name": null, "date": "2023 Feb 13", "date_precision": "day", "issue": "1", "normalized_date": "2023-02-13", "pages": "2554", "proceedings_title": null, "publisher": "", "title": "Scientific reports", "volume": "13", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Ab-GALFA, A bioassay for insect gall formation using the model plant Arabidopsis thaliana.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Proper regulation of apoptotic cell death is crucial for normal development and homeostasis in multicellular organisms, and is achieved by the balance between pro-apoptotic processes, such as caspase activation, and pro-survival signaling, such as extracellular signal-regulated kinase (ERK) activation. However, the functional interplay between these opposing signaling pathways remains incompletely understood. Here, we identified MAPK/ERK kinase (MEK) 1, a central component of the ERK pathway, as a specific substrate for the executioner caspase-3. During apoptosis, MEK1 is cleaved at an evolutionarily conserved Asp282 residue in the kinase domain, thereby losing its catalytic activity. Gene knockout experiments showed that MEK1 cleavage was mediated by caspase-3, but not by the other executioner caspases, caspase-6 or -7. Following exposure of cells to osmotic stress, elevated ERK activity gradually decreased and this was accompanied by increased cleavage of MEK1. In contrast, expression of a caspase-uncleavable MEK1(D282N) mutant in cells maintained stress-induced ERK activity and thereby attenuated apoptotic cell death. Thus, caspase-3-mediated, proteolytic inhibition of MEK1 sensitizes cells to apoptosis by suppressing pro-survival ERK signaling. Furthermore, we found that a RASopathy-associated MEK1(Y130C) mutation prevented this caspase-3-mediated proteolytic inactivation of MEK1 and efficiently protected cells from stress-induced apoptosis. Our data reveal the functional crosstalk between ERK-mediated cell survival and caspase-mediated cell death pathways, and suggest that its dysregulation by a disease-associated MEK1 mutation is at least partly involved in the pathophysiology of congenital RASopathies.", "classifications": [ { "id": "JPMJCR2022", "label": "JPMJCR2022", "researcher": "Mutsuhiro Takekawa", "type": "grant" }, { "id": "Takekawa", "label": "Group Takekawa", "parent": "Takekawa", "type": "group" }, { "id": "Takekawa", "label": "Team Takekawa", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Hisashi", "last_name": "Moriizumi", "name": null }, { "creator_type": "author", "first_name": "Yuji", "last_name": "Kubota", "name": null }, { "creator_type": "author", "first_name": "Tomoyuki", "last_name": "Tsuchiya", "name": null }, { "creator_type": "author", "first_name": "Ryosuke", "last_name": "Naka", "name": null }, { "creator_type": "author", "first_name": "Mutsuhiro", "last_name": "Takekawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/2211-5463.13574" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "36776127" } }, "mesh": [ { "descriptor": "Apoptosis", "descriptor_ui": "D017209", "major_topic": false }, { "descriptor": "Caspase 3", "descriptor_ui": "D053148", "major_topic": false }, { "descriptor": "Caspases", "descriptor_ui": "D020169", "major_topic": false }, { "descriptor": "Extracellular Signal-Regulated MAP Kinases", "descriptor_ui": "D048049", "major_topic": true }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": true } ], "publication": { "conference_name": null, "date": "2023 Feb 13", "date_precision": "day", "issue": "", "normalized_date": "2023-02-13", "pages": "", "proceedings_title": null, "publisher": "", "title": "FEBS open bio", "volume": "", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Caspase 3-specific cleavage of MEK1 suppresses ERK signaling and sensitizes cells to stress-induced apoptosis.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "", "classifications": [ { "id": "Iwaki", "label": "Group Iwaki", "parent": "Toyoshima", "type": "group" }, { "id": "Toyoshima", "label": "Team Toyoshima", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Mitsuhiro", "last_name": "Iwaki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.bpj.2022.11.264" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "36784909" } }, "mesh": [], "publication": { "conference_name": null, "date": "2023 Feb 10", "date_precision": "day", "issue": "3S1", "normalized_date": "2023-02-10", "pages": "5a", "proceedings_title": null, "publisher": "", "title": "Biophysical journal", "volume": "122", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Dynamic coordination of the lever-arm swing of myosin II in DNA origami-based thick filament.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Symmetric tissue alignment is pivotal to the functions of plant vascular tissue, such as long-distance molecular transport and lateral organ formation. During the vascular development of the Arabidopsis roots, cytokinins initially determine cell-type boundaries among vascular stem cells and subsequently promote cell proliferation to establish vascular tissue symmetry. Although it is unknown whether and how the symmetry of initially defined boundaries is progressively refined under tissue growth in plants, such boundary shapes in animal tissues are regulated by cell fluidity, e.g., cell migration and intercalation, lacking in plant tissues. Here, we uncover that cell proliferation during vascular development produces anisotropic compressive stress, smoothing, and symmetrizing cell arrangement of the vascular-cell-type boundary. Mechanistically, the GATA transcription factor HANABA-TARANU cooperates with the type-B Arabidopsis response regulators to form an incoherent feedforward loop in cytokinin signaling. The incoherent feedforward loop fine-tunes the position and frequency of vascular cell proliferation, which in turn restricts the source of mechanical stress to the position distal and symmetric to the boundary. By combinatorial analyses of mechanical simulations and laser cell ablation, we show that the spatially constrained environment of vascular tissue efficiently entrains the stress orientation among the cells to produce a tissue-wide stress field. Together, our data indicate that the localized proliferation regulated by the cytokinin signaling circuit is decoded into a globally oriented mechanical stress to shape the vascular tissue symmetry, representing a reasonable mechanism controlling the boundary alignment and symmetry in tissue lacking cell fluidity.", "classifications": [ { "id": "JPMJCR2121", "label": "JPMJCR2121", "researcher": "Minako Ueda", "type": "grant" }, { "id": "Fujimoto", "label": "Group Fujimoto", "parent": "Ueda", "type": "group" }, { "id": "Ueda", "label": "Group Ueda", "parent": "Ueda", "type": "group" }, { "id": "Ueda", "label": "Team Ueda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Motohiro", "last_name": "Fujiwara", "name": null }, { "creator_type": "author", "first_name": "Miyu", "last_name": "Imamura", "name": null }, { "creator_type": "author", "first_name": "Katsuyoshi", "last_name": "Matsushita", "name": null }, { "creator_type": "author", "first_name": "Pawel", "last_name": "Roszak", "name": null }, { "creator_type": "author", "first_name": "Takafumi", "last_name": "Yamashino", "name": null }, { "creator_type": "author", "first_name": "Yoichiroh", "last_name": "Hosokawa", "name": null }, { "creator_type": "author", "first_name": "Keiji", "last_name": "Nakajima", "name": null }, { "creator_type": "author", "first_name": "Koichi", "last_name": "Fujimoto", "name": null }, { "creator_type": "author", "first_name": "Shunsuke", "last_name": "Miyashima", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.cub.2023.01.036" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "36787744" } }, "mesh": [ { "descriptor": "Arabidopsis", "descriptor_ui": "D017360", "major_topic": true }, { "descriptor": "Arabidopsis Proteins", "descriptor_ui": "D029681", "major_topic": true }, { "descriptor": "Cell Proliferation", "descriptor_ui": "D049109", "major_topic": false }, { "descriptor": "Cytokinins", "descriptor_ui": "D003583", "major_topic": false }, { "descriptor": "Gene Expression Regulation, Plant", "descriptor_ui": "D018506", "major_topic": false }, { "descriptor": "Meristem", "descriptor_ui": "D018519", "major_topic": false }, { "descriptor": "Plant Roots", "descriptor_ui": "D018517", "major_topic": false } ], "publication": { "conference_name": null, "date": "2023 Feb 9", "date_precision": "day", "issue": "", "normalized_date": "2023-02-09", "pages": "S0960-9822(23)00070-2", "proceedings_title": null, "publisher": "", "title": "Current biology : CB", "volume": "", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Patterned proliferation orients tissue-wide stress to control root vascular symmetry in Arabidopsis.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "INTRODUCTION: Osimertinib is a third-generation, irreversible, oral epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) that potently and selectively inhibits both EGFR-TKI sensitizing and EGFR T790M resistance mutations, with demonstrated efficacy in EGFR mutation-positive (EGFRm) non-small cell lung cancer (NSCLC), including central nervous system (CNS) metastases. Here we present the rationale and study design for ADAURA2 (NCT05120349), which will evaluate adjuvant osimertinib vs. placebo in patients with stage IA2-IA3 EGFRm NSCLC, following complete tumor resection. PATIENTS AND METHODS: ADAURA2 is a phase III, global, randomized, double-blind, placebo-controlled study. Patients will be adults aged >/=18 years with resected primary nonsquamous NSCLC stage IA2 or IA3 and central confirmation of an EGFR exon 19 deletion or L858R mutation. Patients will be stratified by pathologic risk of disease recurrence (high vs. low), EGFR mutation type (exon 19 deletion vs. L858R) and race (Chinese Asian vs. non-Chinese Asian vs. non-Asian), and randomized 1:1 to receive osimertinib 80 mg once daily (QD) or placebo QD until disease recurrence, treatment discontinuation, or a maximum treatment duration of 3 years. The primary endpoint of this study is disease-free survival (DFS) in the high-risk stratum. Secondary endpoints include DFS in the overall population, overall survival, CNS DFS, and safety. Health-related quality of life and pharmacokinetics will also be evaluated. RESULTS: Study enrolment began in February 2022 and interim results of the primary endpoint are expected in August 2027.", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yasuhiro", "last_name": "Tsutani", "name": null }, { "creator_type": "author", "first_name": "Jonathan W.", "last_name": "Goldman", "name": null }, { "creator_type": "author", "first_name": "Sanja", "last_name": "Dacic", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null }, { "creator_type": "author", "first_name": "Margarita", "last_name": "Majem", "name": null }, { "creator_type": "author", "first_name": "Xiangning", "last_name": "Huang", "name": null }, { "creator_type": "author", "first_name": "Allen", "last_name": "Chen", "name": null }, { "creator_type": "author", "first_name": "Toon", "last_name": "van der Gronde", "name": null }, { "creator_type": "author", "first_name": "Jie", "last_name": "He", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.cllc.2023.02.002" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "36872181" } }, "mesh": [ { "descriptor": "Acrylamides", "descriptor_ui": "D000178", "major_topic": false }, { "descriptor": "Aniline Compounds", "descriptor_ui": "D000814", "major_topic": false }, { "descriptor": "Antineoplastic Agents", "descriptor_ui": "D000970", "major_topic": true }, { "descriptor": "Carcinoma, Non-Small-Cell Lung", "descriptor_ui": "D002289", "major_topic": true }, { "descriptor": "Clinical Trials, Phase III as Topic", "descriptor_ui": "D017326", "major_topic": false }, { "descriptor": "Disease-Free Survival", "descriptor_ui": "D018572", "major_topic": false }, { "descriptor": "Double-Blind Method", "descriptor_ui": "D004311", "major_topic": false }, { "descriptor": "ErbB Receptors", "descriptor_ui": "D066246", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Indoles", "descriptor_ui": "D007211", "major_topic": false }, { "descriptor": "Lung Neoplasms", "descriptor_ui": "D008175", "major_topic": true }, { "descriptor": "Placebos", "descriptor_ui": "D010919", "major_topic": false }, { "descriptor": "Protein Kinase Inhibitors", "descriptor_ui": "D047428", "major_topic": true }, { "descriptor": "Pyrimidines", "descriptor_ui": "D011743", "major_topic": false }, { "descriptor": "Randomized Controlled Trials as Topic", "descriptor_ui": "D016032", "major_topic": false } ], "publication": { "conference_name": null, "date": "2023 Feb 8", "date_precision": "day", "issue": "", "normalized_date": "2023-02-08", "pages": "S1525-7304(23)00020-7", "proceedings_title": null, "publisher": "", "title": "Clinical lung cancer", "volume": "", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Adjuvant Osimertinib vs. Placebo in Completely Resected Stage IA2-IA3 EGFR-Mutated NSCLC: ADAURA2.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "AIMS: Extraskeletal myxoid chondrosarcoma (EMC) is a rare form of adult sarcoma with distinct histology and NR4A3 gene fusion. Immunohistochemically, EMCs are variably positive for S100 protein and neuroendocrine markers. Unlike histologically similar soft-tissue myoepithelial tumors, keratin expression is rare. Prompted by two recent EMC cases with diffuse keratin expression, we investigated the expression of epithelial markers in a molecularly confirmed cohort of EMC and identified two additional similar cases. METHODS AND RESULTS: Four keratin-positive EMCs occurred in one man and three women aged 46-59 years. All tumors displayed non-classic histology with prominent stromal fibrosis, and keratin AE1/AE3 was expressed either diffusely (N = 2) or focally (N = 2). In one tumor, keratin expression was limited to the sclerotic area. All tumors co-expressed epithelial membrane antigen and two additionally expressed S100 protein or glial fibrillary acidic protein. All tumors harbored NR4A3 fusions including TAF15::NR4A3 (N = 1) and EWSR1::NR4A3 (N = 3). Two cases were initially considered as most consistent with myoepithelial tumors based on widespread stromal fibrosis and keratin expression. DNA methylation analysis classified two tumors tested as EMCs. CONCLUSIONS: We identified a small subset of EMCs characterized by keratin expression and prominent stromal fibrosis. This histological pattern must be recognized in the differential diagnosis of myoepithelial tumors because misclassification may lead to the erroneous prediction of tumor behavior and may alter patient management. NR4A3 genetic analysis should be considered even in the face of keratin expression and prominent stromal fibrosis.", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Hirokazu", "last_name": "Sugino", "name": null }, { "creator_type": "author", "first_name": "Shintaro", "last_name": "Iwata", "name": null }, { "creator_type": "author", "first_name": "Kaishi", "last_name": "Satomi", "name": null }, { "creator_type": "author", "first_name": "Taisuke", "last_name": "Mori", "name": null }, { "creator_type": "author", "first_name": "Sumihito", "last_name": "Nobusawa", "name": null }, { "creator_type": "author", "first_name": "Toshiteru", "last_name": "Nagashima", "name": null }, { "creator_type": "author", "first_name": "Yuko", "last_name": "Matsushita", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null }, { "creator_type": "author", "first_name": "Koichi", "last_name": "Ichimura", "name": null }, { "creator_type": "author", "first_name": "Akira", "last_name": "Kawai", "name": null }, { "creator_type": "author", "first_name": "Akihiko", "last_name": "Yoshida", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/his.14882" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "36754860" } }, "mesh": [ { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Calmodulin-Binding Proteins", "descriptor_ui": "D002148", "major_topic": false }, { "descriptor": "Chondrosarcoma", "descriptor_ui": "D002813", "major_topic": true }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Fibrosis", "descriptor_ui": "D005355", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Keratins", "descriptor_ui": "D007633", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Myoepithelioma", "descriptor_ui": "D009208", "major_topic": true }, { "descriptor": "Neoplasms, Connective and Soft Tissue", "descriptor_ui": "D018204", "major_topic": false }, { "descriptor": "RNA-Binding Proteins", "descriptor_ui": "D016601", "major_topic": false }, { "descriptor": "S100 Proteins", "descriptor_ui": "D009418", "major_topic": false }, { "descriptor": "Soft Tissue Neoplasms", "descriptor_ui": "D012983", "major_topic": true } ], "publication": { "conference_name": null, "date": "2023 Feb 8", "date_precision": "day", "issue": "", "normalized_date": "2023-02-08", "pages": "", "proceedings_title": null, "publisher": "", "title": "Histopathology", "volume": "", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Keratin-positive fibrotic extraskeletal myxoid chondrosarcoma: a close mimic of myoepithelial tumor.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Our previous real-world studies raised concerns that sequential biomarker testing may lead to increased time to treatment when compared with simultaneous single biomarker testing. The Oncomine Dx target test (ODxTT), a next-generation sequencing-based multiplex biomarker panel test approved in Japan in 2019, is expected to improve time to treatment due to changes in testing methods. This retrospective observational study examined data claims for reimbursement submitted for patients with lung cancer in Japan between June 1, 2019, and March 31, 2020. To evaluate the change in testing prevalence over time and associated improvements in time to treatment (TTT), descriptive statistics were used to characterize biomarker testing patterns and rates and evaluate the TTT in the time following the approval of ODxTT considering transitions over time during the evaluation period. EGFR and programmed death ligand 1 (PD-L1) were the most tested biomarkers in overall single and simultaneous single testing in the 6177 patients in this study. Individual single biomarker testing gradually decreased over time, except testing for PD-L1, which remained constant. The use of ODxTT gradually increased in this period. TTT was decreased from 29 to 22 days with ODxTT, in contrast with single biomarker tests (median, 21-23 days overall). These results indicate that biomarker testing frequency has changed in Japanese clinical practice during the study and that the use of ODxTT has increased over time, which potentially contributed to the shortening of TTT.", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Toshiaki", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Nishio", "name": null }, { "creator_type": "author", "first_name": "Kazumi", "last_name": "Nishino", "name": null }, { "creator_type": "author", "first_name": "Yasumasa", "last_name": "Yoshiki", "name": null }, { "creator_type": "author", "first_name": "Naoko", "last_name": "Shiraiwa", "name": null }, { "creator_type": "author", "first_name": "Birol", "last_name": "Emir", "name": null }, { "creator_type": "author", "first_name": "Laura", "last_name": "Iadeluca", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null }, { "creator_type": "author", "first_name": "Kazuto", "last_name": "Nishio", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/cas.15752" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "36751989" } }, "mesh": [ { "descriptor": "B7-H1 Antigen", "descriptor_ui": "D060890", "major_topic": false }, { "descriptor": "Biomarkers, Tumor", "descriptor_ui": "D014408", "major_topic": false }, { "descriptor": "Carcinoma, Non-Small-Cell Lung", "descriptor_ui": "D002289", "major_topic": true }, { "descriptor": "High-Throughput Nucleotide Sequencing", "descriptor_ui": "D059014", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Japan", "descriptor_ui": "D007564", "major_topic": false }, { "descriptor": "Lung Neoplasms", "descriptor_ui": "D008175", "major_topic": true }, { "descriptor": "Retrospective Studies", "descriptor_ui": "D012189", "major_topic": false } ], "publication": { "conference_name": null, "date": "2023 Feb 8", "date_precision": "day", "issue": "", "normalized_date": "2023-02-08", "pages": "", "proceedings_title": null, "publisher": "", "title": "Cancer science", "volume": "", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Real-world study of next-generation sequencing diagnostic biomarker testing for patients with lung cancer in Japan.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Alliaceous and cruciferous vegetables are rich in bioactive organosulfur compounds, including polysulfides, which exhibit a broad spectrum of potential health benefits. Here, we developed novel, accurate, and reproducible methods to quantify the total polysulfide content (TPsC) and the reactive polysulfide content (RPsC) using liquid chromatography-electrospray ionization-tandem mass spectrometry, and analyzed the reactive polysulfide profiles of 22 types of fresh vegetables, including onions, garlic, and broccoli. Quantitative analyses revealed that onions contained the largest amounts of polysulfides, followed by broccoli, Chinese chive, and garlic. A strong positive correlation was observed between the TPsC and RPsC, whereas only a moderate positive correlation was found between the total sulfur content and TPsC. These results suggest that reactive polysulfide profiling can be a novel criterion for evaluating the beneficial functions of vegetables and their derivatives, which may lead to an understanding of the detailed mechanisms underlying their bioactivities.", "classifications": [ { "id": "Akaike", "label": "Group Akaike", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Shingo", "last_name": "Kasamatsu", "name": null }, { "creator_type": "author", "first_name": "Ayaka", "last_name": "Kinno", "name": null }, { "creator_type": "author", "first_name": "Jun-Ichi", "last_name": "Hishiyama", "name": null }, { "creator_type": "author", "first_name": "Takaaki", "last_name": "Akaike", "name": null }, { "creator_type": "author", "first_name": "Hideshi", "last_name": "Ihara", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.foodchem.2023.135610" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "36774840" } }, "mesh": [ { "descriptor": "Antioxidants", "descriptor_ui": "D000975", "major_topic": false }, { "descriptor": "Brassica", "descriptor_ui": "D001937", "major_topic": true }, { "descriptor": "Garlic", "descriptor_ui": "D005737", "major_topic": true }, { "descriptor": "Onions", "descriptor_ui": "D019697", "major_topic": false }, { "descriptor": "Sulfides", "descriptor_ui": "D013440", "major_topic": false }, { "descriptor": "Vegetables", "descriptor_ui": "D014675", "major_topic": false } ], "publication": { "conference_name": null, "date": "2023 Feb 4", "date_precision": "day", "issue": "", "normalized_date": "2023-02-04", "pages": "135610", "proceedings_title": null, "publisher": "", "title": "Food chemistry", "volume": "413", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Development of methods for quantitative determination of the total and reactive polysulfides: Reactive polysulfide profiling in vegetables.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The bodies of herbaceous plants are slender, thin, and soft. These plants support their bodies through the action of turgor pressure associated with their internal water stores. The purpose of this study was to apply the principles of structural mechanics to clarify the underlying mechanism of rigidity control that is responsible for turgor pressure in plants and the reason behind the self-supporting ability of herbaceous plants. We modeled a plant a horizontally oriented thin-walled cylindrical cantilever with closed ends enclosing a cavity filled with water that is acted on by its own weight and by internal tension generated through turgor pressure. We derived an equation describing the plant's consequent deflection, introducing a dimensionless parameter to express the decrease in deflection associated with the action of turgor pressure. We found that the mechanical and physical characteristics of herbaceous plants that would appear to be counter-productive from a superficial perspective increase the deflection decreasing effect of turgor pressure.", "classifications": [ { "id": "JPMJCR2121", "label": "JPMJCR2121", "researcher": "Minako Ueda", "type": "grant" }, { "id": "Tsugawa", "label": "Group Tsugawa", "parent": "Ueda", "type": "group" }, { "id": "Ueda", "label": "Group Ueda", "parent": "Ueda", "type": "group" }, { "id": "Ueda", "label": "Team Ueda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Tohya", "last_name": "Kanahama", "name": null }, { "creator_type": "author", "first_name": "Satoru", "last_name": "Tsugawa", "name": null }, { "creator_type": "author", "first_name": "Motohiro", "last_name": "Sato", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41598-023-29294-5" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "36739460" } }, "mesh": [], "publication": { "conference_name": null, "date": "2023 Feb 4", "date_precision": "day", "issue": "1", "normalized_date": "2023-02-04", "pages": "2063", "proceedings_title": null, "publisher": "", "title": "Scientific reports", "volume": "13", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Rigidity control mechanism by turgor pressure in plants.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "NF-E2-related factor 2 (NRF2) plays a crucial role in the maintenance of cellular homeostasis by regulating various enzymes and proteins that are involved in the redox reactions utilizing sulfur. While substantial impacts of NRF2 on mitochondrial activity have been described, the precise mechanism by which NRF2 regulates mitochondrial function is still not fully understood. Here, we demonstrated that NRF2 increased intracellular persulfides by upregulating the cystine transporter xCT encoded by Slc7a11, a well-known NRF2 target gene. Persulfides have been shown to play an important role in mitochondrial function. Supplementation with glutathione trisulfide (GSSSG), which is a form of persulfide, elevated the mitochondrial membrane potential (MMP), increased the oxygen consumption rate (OCR) and promoted ATP production. Persulfide-mediated mitochondrial activation was shown to require the mitochondrial sulfur oxidation pathway, especially sulfide quinone oxidoreductase (SQOR). Consistently, NRF2-mediated mitochondrial activation was also dependent on SQOR activity. This study clarified that the facilitation of persulfide production and sulfur metabolism in mitochondria by increasing cysteine availability is one of the mechanisms for NRF2-dependent mitochondrial activation.", "classifications": [ { "id": "Akaike", "label": "Group Akaike", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Md Morshedul", "last_name": "Alam", "name": null }, { "creator_type": "author", "first_name": "Akihiro", "last_name": "Kishino", "name": null }, { "creator_type": "author", "first_name": "Eunkyu", "last_name": "Sung", "name": null }, { "creator_type": "author", "first_name": "Hiroki", "last_name": "Sekine", "name": null }, { "creator_type": "author", "first_name": "Takaaki", "last_name": "Abe", "name": null }, { "creator_type": "author", "first_name": "Shohei", "last_name": "Murakami", "name": null }, { "creator_type": "author", "first_name": "Takaaki", "last_name": "Akaike", "name": null }, { "creator_type": "author", "first_name": "Hozumi", "last_name": "Motohashi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.redox.2023.102624" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "36758466" } }, "mesh": [ { "descriptor": "Cystine", "descriptor_ui": "D003553", "major_topic": false }, { "descriptor": "Mitochondria", "descriptor_ui": "D008928", "major_topic": false }, { "descriptor": "NF-E2-Related Factor 2", "descriptor_ui": "D051267", "major_topic": true }, { "descriptor": "Sulfides", "descriptor_ui": "D013440", "major_topic": true } ], "publication": { "conference_name": null, "date": "2023 Feb 2", "date_precision": "day", "issue": "", "normalized_date": "2023-02-02", "pages": "102624", "proceedings_title": null, "publisher": "", "title": "Redox biology", "volume": "60", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Contribution of NRF2 to sulfur metabolism and mitochondrial activity.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Induced pluripotent stem cell (iPSC) reprogramming is inefficient and understanding the molecular mechanisms underlying this inefficiency holds the key to successfully control cellular identity. Here, we report 24 reprogramming roadblock genes identified by CRISPR/Cas9-mediated genome-wide knockout (KO) screening. Of these, depletion of the predicted KRAB zinc finger protein (KRAB-ZFP) Zfp266 strongly and consistently enhances murine iPSC generation in several reprogramming settings, emerging as the most robust roadblock. We show that ZFP266 binds Short Interspersed Nuclear Elements (SINEs) adjacent to binding sites of pioneering factors, OCT4 (POU5F1), SOX2, and KLF4, and impedes chromatin opening. Replacing the KRAB co-suppressor with co-activator domains converts ZFP266 from an inhibitor to a potent facilitator of iPSC reprogramming. We propose that the SINE-KRAB-ZFP interaction is a critical regulator of chromatin accessibility at regulatory elements required for efficient cellular identity changes. In addition, this work serves as a resource to further illuminate molecular mechanisms hindering reprogramming.", "classifications": [ { "id": "Yusa", "label": "Group Yusa", "parent": "Eiraku", "type": "group" }, { "id": "Eiraku", "label": "Team Eiraku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Daniel F.", "last_name": "Kaemena", "name": null }, { "creator_type": "author", "first_name": "Masahito", "last_name": "Yoshihara", "name": null }, { "creator_type": "author", "first_name": "Meryam", "last_name": "Beniazza", "name": null }, { "creator_type": "author", "first_name": "James", "last_name": "Ashmore", "name": null }, { "creator_type": "author", "first_name": "Suling", "last_name": "Zhao", "name": null }, { "creator_type": "author", "first_name": "Marten", "last_name": "Bertenstam", "name": null }, { "creator_type": "author", "first_name": "Victor", "last_name": "Olariu", "name": null }, { "creator_type": "author", "first_name": "Shintaro", "last_name": "Katayama", "name": null }, { "creator_type": "author", "first_name": "Keisuke", "last_name": "Okita", "name": null }, { "creator_type": "author", "first_name": "Simon R.", "last_name": "Tomlinson", "name": null }, { "creator_type": "author", "first_name": "Kosuke", "last_name": "Yusa", "name": null }, { "creator_type": "author", "first_name": "Keisuke", "last_name": "Kaji", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41467-023-36097-9" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "36717582" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cellular Reprogramming", "descriptor_ui": "D065150", "major_topic": false }, { "descriptor": "Chromatin", "descriptor_ui": "D002843", "major_topic": false }, { "descriptor": "Induced Pluripotent Stem Cells", "descriptor_ui": "D057026", "major_topic": true }, { "descriptor": "Kruppel-Like Factor 4", "descriptor_ui": "D000090062", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Zinc Fingers", "descriptor_ui": "D016335", "major_topic": true } ], "publication": { "conference_name": null, "date": "2023 Jan 30", "date_precision": "day", "issue": "1", "normalized_date": "2023-01-30", "pages": "488", "proceedings_title": null, "publisher": "", "title": "Nature communications", "volume": "14", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "B1 SINE-binding ZFP266 impedes mouse iPSC generation through suppression of chromatin opening mediated by reprogramming factors.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Choline supplies methyl groups for regeneration of methionine and the methyl donor S-adenosylmethionine in the liver. Here, we report that the catabolism of membrane phosphatidylcholine (PC) into water-soluble glycerophosphocholine (GPC) by the phospholipase/lysophospholipase PNPLA8-PNPLA7 axis enables endogenous choline stored in hepatic PC to be utilized in methyl metabolism. PNPLA7-deficient mice show marked decreases in hepatic GPC, choline, and several metabolites related to the methionine cycle, accompanied by various signs of methionine insufficiency, including growth retardation, hypoglycemia, hypolipidemia, increased energy consumption, reduced adiposity, increased fibroblast growth factor 21 (FGF21), and an altered histone/DNA methylation landscape. Moreover, PNPLA8-deficient mice recapitulate most of these phenotypes. In contrast to wild-type mice fed a methionine/choline-deficient diet, both knockout strains display decreased hepatic triglyceride, likely via reductions of lipogenesis and GPC-derived glycerol flux. Collectively, our findings highlight the biological importance of phospholipid catabolism driven by PNPLA8/PNPLA7 in methyl group flux and triglyceride synthesis in the liver.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Tetsuya", "last_name": "Hirabayashi", "name": null }, { "creator_type": "author", "first_name": "Mai", "last_name": "Kawaguchi", "name": null }, { "creator_type": "author", "first_name": "Sayaka", "last_name": "Harada", "name": null }, { "creator_type": "author", "first_name": "Misa", "last_name": "Mouri", "name": null }, { "creator_type": "author", "first_name": "Rina", "last_name": "Takamiya", "name": null }, { "creator_type": "author", "first_name": "Yoshimi", "last_name": "Miki", "name": null }, { "creator_type": "author", "first_name": "Hiroyasu", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Yoshitaka", "last_name": "Taketomi", "name": null }, { "creator_type": "author", "first_name": "Kohei", "last_name": "Yokoyama", "name": null }, { "creator_type": "author", "first_name": "Tetsuyuki", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Suzumi M.", "last_name": "Tokuoka", "name": null }, { "creator_type": "author", "first_name": "Yoshihiro", "last_name": "Kita", "name": null }, { "creator_type": "author", "first_name": "Emiko", "last_name": "Yoda", "name": null }, { "creator_type": "author", "first_name": "Shuntaro", "last_name": "Hara", "name": null }, { "creator_type": "author", "first_name": "Kyohei", "last_name": "Mikami", "name": null }, { "creator_type": "author", "first_name": "Yasumasa", "last_name": "Nishito", "name": null }, { "creator_type": "author", "first_name": "Norihito", "last_name": "Kikuchi", "name": null }, { "creator_type": "author", "first_name": "Rieko", "last_name": "Nakata", "name": null }, { "creator_type": "author", "first_name": "Mari", "last_name": "Kaneko", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Kiyonari", "name": null }, { "creator_type": "author", "first_name": "Kohji", "last_name": "Kasahara", "name": null }, { "creator_type": "author", "first_name": "Toshiki", "last_name": "Aiba", "name": null }, { "creator_type": "author", "first_name": "Kazutaka", "last_name": "Ikeda", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Kurano", "name": null }, { "creator_type": "author", "first_name": "Yutaka", "last_name": "Yatomi", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Murakami", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.celrep.2022.111940" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "36719796" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Carboxylic Ester Hydrolases", "descriptor_ui": "D002265", "major_topic": false }, { "descriptor": "Choline", "descriptor_ui": "D002794", "major_topic": false }, { "descriptor": "Glycerylphosphorylcholine", "descriptor_ui": "D005997", "major_topic": false }, { "descriptor": "Liver", "descriptor_ui": "D008099", "major_topic": true }, { "descriptor": "Lysophospholipase", "descriptor_ui": "D008245", "major_topic": true }, { "descriptor": "Methionine", "descriptor_ui": "D008715", "major_topic": true }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Phosphatidylcholines", "descriptor_ui": "D010713", "major_topic": true }, { "descriptor": "Racemethionine", "descriptor_ui": "D064697", "major_topic": false }, { "descriptor": "S-Adenosylmethionine", "descriptor_ui": "D012436", "major_topic": false }, { "descriptor": "Triglycerides", "descriptor_ui": "D014280", "major_topic": false } ], "publication": { "conference_name": null, "date": "2023 Jan 30", "date_precision": "day", "issue": "2", "normalized_date": "2023-01-30", "pages": "111940", "proceedings_title": null, "publisher": "", "title": "Cell reports", "volume": "42", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Hepatic phosphatidylcholine catabolism driven by PNPLA7 and PNPLA8 supplies endogenous choline to replenish the methionine cycle with methyl groups.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The redox behaviors of macrocyclic molecules with an entirely π-conjugated system are of interest due to their unique optical, electronic, and magnetic properties. In this study, defect-free cyclic P3HT with a degree of polymerization (DP(n)) from 14 to 43 was synthesized based on our previously established method, and its unique redox behaviors arising from the cyclic topology were investigated. Cyclic voltammetry (CV) showed that the HOMO level of cyclic P3HT decreases from -4.86 eV (14 mer) to -4.89 eV (43 mer), in contrast to the linear counterparts increasing from -4.94 eV (14 mer) to -4.91 eV (43 mer). During the CV measurement, linear P3HT suffered from electro-oxidation at the chain ends, while cyclic P3HT was stable. ESR and UV-Vis-NIR spectroscopy suggested that cyclic P3HT has stronger dicationic properties due to the interactions between the polarons. On the other hand, linear P3HT showed characteristics of polaron pairs with multiple isolated polarons. Moreover, the dicationic properties of cyclic P3HT were more pronounced for the smaller macrocycles.", "classifications": [ { "id": "Yamamoto", "label": "Group Yamamoto", "parent": "Toyoshima", "type": "group" }, { "id": "Toyoshima", "label": "Team Toyoshima", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Ryohei", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Atsuo", "last_name": "Utagawa", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Fushimi", "name": null }, { "creator_type": "author", "first_name": "Feng", "last_name": "Li", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Isono", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Tajima", "name": null }, { "creator_type": "author", "first_name": "Toshifumi", "last_name": "Satoh", "name": null }, { "creator_type": "author", "first_name": "Shin-Ichiro", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Hirata", "name": null }, { "creator_type": "author", "first_name": "Yoshihiro", "last_name": "Kikkawa", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Yamamoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.3390/polym15030666" }, "pmcid": { "normalized": "PMC9920727" }, "pmid": { "normalized": "36771966" } }, "mesh": [], "publication": { "conference_name": null, "date": "2023 Jan 28", "date_precision": "day", "issue": "3", "normalized_date": "2023-01-28", "pages": "", "proceedings_title": null, "publisher": "", "title": "Polymers", "volume": "15", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Molecular Weight-Dependent Oxidation and Optoelectronic Properties of Defect-Free Macrocyclic Poly(3-hexylthiophene).", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "OBJECTIVES: With recent improvements in surgical techniques for segmentectomy, we hypothesized that segmentectomy is feasible and more effective than wedge resection for non-small cell lung cancer (NSCLC). We compared perioperative and oncological outcomes for segmentectomy and wedge resection. METHODS: We performed a retrospective analysis of 720 patients who underwent sublobar resection (segmentectomy, 479; wedge resection, 241) for clinical stage 0 or I NSCLC from January 2017 to June 2020. An adequate surgical margin was defined as a surgical margin distance of >/= 2 cm or >/= the total tumour size. Recurrence-free survival (RFS) was estimated using the Kaplan-Meier method for clinical stage IA. RESULTS: There was no significant difference in the rate of major (grade >/= III) complications between segmentectomy (1.7%) and wedge resection (1.2%) (P = 0.76). The probability of obtaining adequate surgical margins was significantly higher with segmentectomy (71.4%) versus wedge resection (59.5%) (P = 0.002), and the difference was especially prominent for clinical stage IA2 (75.3% vs 56.9%; P = 0.012). Among patients with clinical stage IA, segmentectomy significantly improved the RFS compared with wedge resection (hazard ratio 2.7; 95% confidence interval 1.60-4.61; log-rank P < 0.001). Subgroup analysis based on tumour status revealed that segmentectomy had a better RFS in clinical stage IA2 (P < 0.001) and in pure-solid tumors (P = 0.022) than wedge resection. CONCLUSIONS: We demonstrate that segmentectomy is a feasible procedure with comparable safety outcomes and better surgical margins and cancer control than wedge resection, particularly for clinical stage IA2 NSCLC.", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Takaki", "last_name": "Akamine", "name": null }, { "creator_type": "author", "first_name": "Masaya", "last_name": "Yotsukura", "name": null }, { "creator_type": "author", "first_name": "Yukihiro", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Kazuo", "last_name": "Nakagawa", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null }, { "creator_type": "author", "first_name": "Shun-Ichi", "last_name": "Watanabe", "name": null } ], "identifiers": { "doi": { "normalized": "10.1093/ejcts/ezad018" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "36708001" } }, "mesh": [ { "descriptor": "Carcinoma, Non-Small-Cell Lung", "descriptor_ui": "D002289", "major_topic": true }, { "descriptor": "Feasibility Studies", "descriptor_ui": "D005240", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Lung Neoplasms", "descriptor_ui": "D008175", "major_topic": true }, { "descriptor": "Margins of Excision", "descriptor_ui": "D000072662", "major_topic": false }, { "descriptor": "Neoplasm Staging", "descriptor_ui": "D009367", "major_topic": false }, { "descriptor": "Pneumonectomy", "descriptor_ui": "D011013", "major_topic": false }, { "descriptor": "Retrospective Studies", "descriptor_ui": "D012189", "major_topic": false } ], "publication": { "conference_name": null, "date": "2023 Jan 27", "date_precision": "day", "issue": "", "normalized_date": "2023-01-27", "pages": "ezad018", "proceedings_title": null, "publisher": "", "title": "European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery", "volume": "", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Feasibility and effectiveness of segmentectomy versus wedge resection for clinical stage I non-small cell lung cancer.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Plant cells are surrounded by a cell wall and do not migrate, which makes the regulation of cell division orientation crucial for development. Regulatory mechanisms controlling cell division orientation may have contributed to the evolution of body organization in land plants. The GRAS family of transcription factors was transferred horizontally from soil bacteria to an algal common ancestor of land plants. SHORTROOT (SHR) and SCARECROW (SCR) genes in this family regulate formative periclinal cell divisions in the roots of flowering plants, but their roles in nonflowering plants and their evolution have not been studied in relation to body organization. Here, we show that SHR cell autonomously inhibits formative periclinal cell divisions indispensable for leaf vein formation in the moss Physcomitrium patens, and SHR expression is positively and negatively regulated by SCR and the GRAS member LATERAL SUPPRESSOR, respectively. While precursor cells of a leaf vein lacking SHR usually follow the geometry rule of dividing along the division plane with the minimum surface area, SHR overrides this rule and forces cells to divide nonpericlinally. Together, these results imply that these bacterially derived GRAS transcription factors were involved in the establishment of the genetic regulatory networks modulating cell division orientation in the common ancestor of land plants and were later adapted to function in flowering plant and moss lineages for their specific body organizations.", "classifications": [ { "id": "Fujimoto", "label": "Group Fujimoto", "parent": "Ueda", "type": "group" }, { "id": "Ueda", "label": "Team Ueda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Masaki", "last_name": "Ishikawa", "name": null }, { "creator_type": "author", "first_name": "Ayaka", "last_name": "Fujiwara", "name": null }, { "creator_type": "author", "first_name": "Ken", "last_name": "Kosetsu", "name": null }, { "creator_type": "author", "first_name": "Yuta", "last_name": "Horiuchi", "name": null }, { "creator_type": "author", "first_name": "Naoya", "last_name": "Kamamoto", "name": null }, { "creator_type": "author", "first_name": "Naoyuki", "last_name": "Umakawa", "name": null }, { "creator_type": "author", "first_name": "Yosuke", "last_name": "Tamada", "name": null }, { "creator_type": "author", "first_name": "Liechi", "last_name": "Zhang", "name": null }, { "creator_type": "author", "first_name": "Katsuyoshi", "last_name": "Matsushita", "name": null }, { "creator_type": "author", "first_name": "Gergo", "last_name": "Palfalvi", "name": null }, { "creator_type": "author", "first_name": "Tomoaki", "last_name": "Nishiyama", "name": null }, { "creator_type": "author", "first_name": "Sota", "last_name": "Kitasaki", "name": null }, { "creator_type": "author", "first_name": "Yuri", "last_name": "Masuda", "name": null }, { "creator_type": "author", "first_name": "Yoshiki", "last_name": "Shiroza", "name": null }, { "creator_type": "author", "first_name": "Munenori", "last_name": "Kitagawa", "name": null }, { "creator_type": "author", "first_name": "Toru", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Hongchang", "last_name": "Cui", "name": null }, { "creator_type": "author", "first_name": "Yuji", "last_name": "Hiwatashi", "name": null }, { "creator_type": "author", "first_name": "Yukiko", "last_name": "Kabeya", "name": null }, { "creator_type": "author", "first_name": "Shuji", "last_name": "Shigenobu", "name": null }, { "creator_type": "author", "first_name": "Tsuyoshi", "last_name": "Aoyama", "name": null }, { "creator_type": "author", "first_name": "Kagayaki", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Murata", "name": null }, { "creator_type": "author", "first_name": "Koichi", "last_name": "Fujimoto", "name": null }, { "creator_type": "author", "first_name": "Philip N.", "last_name": "Benfey", "name": null }, { "creator_type": "author", "first_name": "Mitsuyasu", "last_name": "Hasebe", "name": null }, { "creator_type": "author", "first_name": "Rumiko", "last_name": "Kofuji", "name": null } ], "identifiers": { "doi": { "normalized": "10.1073/pnas.2210632120" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "36669117" } }, "mesh": [ { "descriptor": "Arabidopsis", "descriptor_ui": "D017360", "major_topic": true }, { "descriptor": "Arabidopsis Proteins", "descriptor_ui": "D029681", "major_topic": true }, { "descriptor": "Cell Division", "descriptor_ui": "D002455", "major_topic": false }, { "descriptor": "Gene Expression Regulation, Plant", "descriptor_ui": "D018506", "major_topic": false }, { "descriptor": "Plant Roots", "descriptor_ui": "D018517", "major_topic": false }, { "descriptor": "Transcription Factors", "descriptor_ui": "D014157", "major_topic": false } ], "publication": { "conference_name": null, "date": "2023 Jan 24", "date_precision": "day", "issue": "4", "normalized_date": "2023-01-24", "pages": "e2210632120", "proceedings_title": null, "publisher": "", "title": "Proceedings of the National Academy of Sciences of the United States of America", "volume": "120", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "GRAS transcription factors regulate cell division planes in moss overriding the default rule.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Constitutive activation of the mitogen-activated protein kinase (MAPK) signaling pathway is essential for tumorigenesis of pancreatic ductal adenocarcinoma (PDAC). To date, however, almost all clinical trials of inhibitors targeting this pathway have failed to improve the outcome of patients with PDAC. We have found that implanted MIA Paca2, a human PDAC cell line sensitive to a MAPK inhibitor, PD0325901, became refractory within a week after the treatment. By comparing the expression profiles of MIA Paca2 before and after acquisition of the refractoriness to PD0325901, we identified clusterin (CLU) as a candidate gene involved. CLU was shown to be induced immediately after treatment with PD0325901 or expressed primarily in more than half of PDAC cell lines, enhancing cell viability by escaping from apoptosis. A combination of PD0325901 and CLU downregulation was found to synergistically or additively reduce the proliferation of PDAC cells. In surgically resected PDAC tissues, overexpression of CLU in cancer cells was observed immunohistochemically in approximately half of the cases studied. Collectively, our findings highlight the mechanisms responsible for the rapid refractory response to MEK inhibitor in PDAC cells, suggesting a novel therapeutic strategy that could be applicable to patients with PDAC using inhibitors targeting the MAPK signaling pathway and CLU.", "classifications": [ { "id": "Takekawa", "label": "Group Takekawa", "parent": "Takekawa", "type": "group" }, { "id": "Takekawa", "label": "Team Takekawa", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Kohei", "last_name": "Amada", "name": null }, { "creator_type": "author", "first_name": "Naoki", "last_name": "Hijiya", "name": null }, { "creator_type": "author", "first_name": "Sawa", "last_name": "Ikarimoto", "name": null }, { "creator_type": "author", "first_name": "Kazuyoshi", "last_name": "Yanagihara", "name": null }, { "creator_type": "author", "first_name": "Toshikatsu", "last_name": "Hanada", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Hidano", "name": null }, { "creator_type": "author", "first_name": "Shusaku", "last_name": "Kurogi", "name": null }, { "creator_type": "author", "first_name": "Yoshiyuki", "last_name": "Tsukamoto", "name": null }, { "creator_type": "author", "first_name": "Chisato", "last_name": "Nakada", "name": null }, { "creator_type": "author", "first_name": "Keisuke", "last_name": "Kinoshita", "name": null }, { "creator_type": "author", "first_name": "Yuka", "last_name": "Hirashita", "name": null }, { "creator_type": "author", "first_name": "Tomohisa", "last_name": "Uchida", "name": null }, { "creator_type": "author", "first_name": "Toshitaka", "last_name": "Shin", "name": null }, { "creator_type": "author", "first_name": "Kazuhiro", "last_name": "Yada", "name": null }, { "creator_type": "author", "first_name": "Teijiro", "last_name": "Hirashita", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Kazunari", "last_name": "Murakami", "name": null }, { "creator_type": "author", "first_name": "Masafumi", "last_name": "Inomata", "name": null }, { "creator_type": "author", "first_name": "Kuniaki", "last_name": "Shirao", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Aoki", "name": null }, { "creator_type": "author", "first_name": "Mutsuhiro", "last_name": "Takekawa", "name": null }, { "creator_type": "author", "first_name": "Masatsugu", "last_name": "Moriyama", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/cas.15735" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "36694355" } }, "mesh": [ { "descriptor": "Benzamides", "descriptor_ui": "D001549", "major_topic": false }, { "descriptor": "Carcinoma, Pancreatic Ductal", "descriptor_ui": "D021441", "major_topic": true }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Cell Proliferation", "descriptor_ui": "D049109", "major_topic": false }, { "descriptor": "Clusterin", "descriptor_ui": "D051152", "major_topic": false }, { "descriptor": "Diphenylamine", "descriptor_ui": "D004159", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mitogen-Activated Protein Kinase Kinases", "descriptor_ui": "D020929", "major_topic": false }, { "descriptor": "Mitogen-Activated Protein Kinases", "descriptor_ui": "D020928", "major_topic": false }, { "descriptor": "Pancreatic Neoplasms", "descriptor_ui": "D010190", "major_topic": true }, { "descriptor": "Protein Kinase Inhibitors", "descriptor_ui": "D047428", "major_topic": false } ], "publication": { "conference_name": null, "date": "2023 Jan 24", "date_precision": "day", "issue": "", "normalized_date": "2023-01-24", "pages": "", "proceedings_title": null, "publisher": "", "title": "Cancer science", "volume": "", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Involvement of clusterin expression in the refractory response of pancreatic cancer cells to a MEK inhibitor.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Memory-limited partially observable stochastic control (ML-POSC) is the stochastic optimal control problem under incomplete information and memory limitation. To obtain the optimal control function of ML-POSC, a system of the forward Fokker-Planck (FP) equation and the backward Hamilton-Jacobi-Bellman (HJB) equation needs to be solved. In this work, we first show that the system of HJB-FP equations can be interpreted via Pontryagin's minimum principle on the probability density function space. Based on this interpretation, we then propose the forward-backward sweep method (FBSM) for ML-POSC. FBSM is one of the most basic algorithms for Pontryagin's minimum principle, which alternately computes the forward FP equation and the backward HJB equation in ML-POSC. Although the convergence of FBSM is generally not guaranteed in deterministic control and mean-field stochastic control, it is guaranteed in ML-POSC because the coupling of the HJB-FP equations is limited to the optimal control function in ML-POSC.", "classifications": [ { "id": "Kobayashi", "label": "Group Kobayashi", "parent": "Wakamoto", "type": "group" }, { "id": "Wakamoto", "label": "Team Wakamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Takehiro", "last_name": "Tottori", "name": null }, { "creator_type": "author", "first_name": "Tetsuya J.", "last_name": "Kobayashi", "name": null } ], "identifiers": { "doi": { "normalized": "10.3390/e25020208" }, "pmcid": { "normalized": "PMC9955073" }, "pmid": { "normalized": "36832575" } }, "mesh": [], "publication": { "conference_name": null, "date": "2023 Jan 21", "date_precision": "day", "issue": "2", "normalized_date": "2023-01-21", "pages": "", "proceedings_title": null, "publisher": "", "title": "Entropy (Basel, Switzerland)", "volume": "25", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Forward-Backward Sweep Method for the System of HJB-FP Equations in Memory-Limited Partially Observable Stochastic Control.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Defect-free one-handed contracted helical tubular ladder polymers with a pi-electron-rich cylindrical helical cavity were synthesized by alkyne benzannulations of the random-coil precursor polymers containing 6,6 -linked-1,1 -spirobiindane-7,7 -diol-based chiral monomer units. The resulting tightly-twisted helical tubular ladder polymers showed remarkably high enantioseparation abilities toward a variety of chiral hydrophobic aromatics with point, axial, and planar chiralities. The random-coil precursor polymer and analogous rigid-rod extended helical ribbon-like ladder polymer with no internal helical cavity exhibited no resolution abilities. The molecular dynamics simulations suggested that the pi-electron-rich cylindrical helical cavity formed in the tightly-twisted tubular helical ladder structures is of key importance for producing the highly-enantioseparation ability, by which chiral aromatics can be enantioselectively encapsulated by specific pi-pi and/or hydrophobic interactions.", "classifications": [ { "id": "Hijikata", "label": "Group Hijikata", "parent": "Tsuchiya", "type": "group" }, { "id": "Tsuchiya", "label": "Team Tsuchiya", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Wei", "last_name": "Zheng", "name": null }, { "creator_type": "author", "first_name": "Kosuke", "last_name": "Oki", "name": null }, { "creator_type": "author", "first_name": "Ranajit", "last_name": "Saha", "name": null }, { "creator_type": "author", "first_name": "Yuh", "last_name": "Hijikata", "name": null }, { "creator_type": "author", "first_name": "Eiji", "last_name": "Yashima", "name": null }, { "creator_type": "author", "first_name": "Tomoyuki", "last_name": "Ikai", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/anie.202218297" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "36680515" } }, "mesh": [], "publication": { "conference_name": null, "date": "2023 Jan 21", "date_precision": "day", "issue": "", "normalized_date": "2023-01-21", "pages": "", "proceedings_title": null, "publisher": "", "title": "Angewandte Chemie (International ed. in English)", "volume": "", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "One-Handed Helical Tubular Ladder Polymers for Chromatographic Enantioseparation.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "In the sexual reproduction of flowering plants, two independent fertilization events occur almost simultaneously: two identical sperm cells fuse with either the egg cell or the central cell, resulting in embryo and endosperm development to produce a seed. GCS1/HAP2 is a sperm cell membrane protein essential for plasma membrane fusion with both female gametes. Other sperm membrane proteins, DMP8 and DMP9, are more important for egg cell fertilization than that of the central cell, suggesting its regulatory mechanism in GCS1/HAP2-driving gamete membrane fusion. To assess the GCS1/HAP2 regulatory cascade in the double fertilization system of flowering plants, we produced Arabidopsis transgenic lines expressing different GCS1/HAP2 variants and evaluated the fertilization in vivo. The fertilization pattern observed in GCS1_RNAi transgenic plants implied that sperm cells over the amount of GCS1/HAP2 required for fusion on their surface could facilitate membrane fusion with both female gametes. The cytological analysis of the dmp8dmp9 sperm cell arrested alone in an embryo sac supported GCS1/HAP2 distribution on the sperm surface. Furthermore, the fertilization failures with both female gametes were caused by GCS1/HAP2 secretion from the egg cell. These results provided a possible scenario of GCS1/HAP2 regulation, showing a potential scheme for capturing additional GCS1/HAP2-interacting proteins.", "classifications": [ { "id": "Ueda", "label": "Group Ueda", "parent": "Ueda", "type": "group" }, { "id": "Ueda", "label": "Team Ueda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yuka", "last_name": "Shiba", "name": null }, { "creator_type": "author", "first_name": "Taro", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Yukino", "last_name": "Ohashi", "name": null }, { "creator_type": "author", "first_name": "Minako", "last_name": "Ueda", "name": null }, { "creator_type": "author", "first_name": "Amane", "last_name": "Mimuro", "name": null }, { "creator_type": "author", "first_name": "Jin", "last_name": "Sugimoto", "name": null }, { "creator_type": "author", "first_name": "Yuka", "last_name": "Noguchi", "name": null }, { "creator_type": "author", "first_name": "Tomoko", "last_name": "Igawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.3390/biom13020208" }, "pmcid": { "normalized": "PMC9953686" }, "pmid": { "normalized": "36830580" } }, "mesh": [ { "descriptor": "Arabidopsis", "descriptor_ui": "D017360", "major_topic": true }, { "descriptor": "Arabidopsis Proteins", "descriptor_ui": "D029681", "major_topic": true }, { "descriptor": "Carrier Proteins", "descriptor_ui": "D002352", "major_topic": false }, { "descriptor": "Fertilization", "descriptor_ui": "D005306", "major_topic": false }, { "descriptor": "Germ Cells", "descriptor_ui": "D005854", "major_topic": false }, { "descriptor": "Seeds", "descriptor_ui": "D012639", "major_topic": false } ], "publication": { "conference_name": null, "date": "2023 Jan 20", "date_precision": "day", "issue": "2", "normalized_date": "2023-01-20", "pages": "", "proceedings_title": null, "publisher": "", "title": "Biomolecules", "volume": "13", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Behavior of Male Gamete Fusogen GCS1/HAP2 and the Regulation in Arabidopsis Double Fertilization.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Animals' sensory systems adjust their responsiveness to environmental stimuli that vary greatly in their intensity. Here we report the neural mechanism of experience-dependent sensory adjustment, especially gain control, in the ASH nociceptive neurons in Caenorhabditis elegans. Using calcium imaging under gradual changes in stimulus intensity, we find that the ASH neurons of naive animals respond to concentration increases in a repulsive odor 2-nonanone regardless of the magnitude of the concentration increase. However, after preexposure to the odor, the ASH neurons exhibit significantly weak responses to a small gradual increase in odor concentration while their responses to a large gradual increase remain strong. Thus, preexposure changes the slope of stimulus-response relationships (i.e., gain control). Behavioral analysis suggests that this gain control contributes to the preexposure-dependent enhancement of odor avoidance behavior. Mathematical analysis reveals that the ASH response consists of fast and slow components, and that the fast component is specifically suppressed by preexposure. In addition, genetic analysis suggests that G protein signaling may be required for the regulation of fast component. We propose how prior experience dynamically and specifically modulates stimulus-response relationships in sensory neurons, eventually leading to adaptive modulation of behavior.", "classifications": [ { "id": "Fujimoto", "label": "Group Fujimoto", "parent": "Ueda", "type": "group" }, { "id": "Ueda", "label": "Team Ueda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yosuke", "last_name": "Ikejiri", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Tanimoto", "name": null }, { "creator_type": "author", "first_name": "Kosuke", "last_name": "Fujita", "name": null }, { "creator_type": "author", "first_name": "Fumie", "last_name": "Hiramatsu", "name": null }, { "creator_type": "author", "first_name": "Shuhei J.", "last_name": "Yamazaki", "name": null }, { "creator_type": "author", "first_name": "Yuto", "last_name": "Endo", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Iwatani", "name": null }, { "creator_type": "author", "first_name": "Koichi", "last_name": "Fujimoto", "name": null }, { "creator_type": "author", "first_name": "Koutarou D.", "last_name": "Kimura", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.neures.2023.01.006" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "36681153" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Caenorhabditis elegans", "descriptor_ui": "D017173", "major_topic": true }, { "descriptor": "Caenorhabditis elegans Proteins", "descriptor_ui": "D029742", "major_topic": true }, { "descriptor": "Nociceptors", "descriptor_ui": "D009619", "major_topic": false }, { "descriptor": "Sensory Receptor Cells", "descriptor_ui": "D011984", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false } ], "publication": { "conference_name": null, "date": "2023 Jan 18", "date_precision": "day", "issue": "", "normalized_date": "2023-01-18", "pages": "S0168-0102(23)00006-8", "proceedings_title": null, "publisher": "", "title": "Neuroscience research", "volume": "", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Neural mechanism of experience-dependent sensory gain control in C. elegans.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The Drosophila behavior/human splicing protein family is involved in numerous steps of gene regulation. In humans, this family consists of three proteins: SFPQ, PSPC1, and NONO. Hemizygous loss-of-function (LoF) variants in NONO cause a developmental delay with several complications (e.g., distinctive facial features, cardiac symptoms, and skeletal symptoms) in an X-linked recessive manner. Most of the reported variants have been LoF variants, and two missense variants have been reported as likely deleterious but with no functional validation. We report three individuals from two families harboring an identical missense variant that is located in the nuclear localization signal, NONO: NM_001145408.2:c.1375C > G p.(Pro459Ala). All of them were male and the variant was inherited from their asymptomatic mothers. Individual 1 was diagnosed with developmental delay and cardiac phenotypes (ventricular tachycardia and dilated cardiomyopathy), which overlapped with the features of reported individuals having NONO LoF variants. Individuals 2 and 3 were monozygotic twins. Unlike in Individual 1, developmental delay with autistic features was the only symptom found in them. A fly experiment and cell localization experiment showed that the NONO variant impaired its proper intranuclear localization, leading to mild LoF. Our findings suggest that deleterious NONO missense variants should be taken into consideration when whole-exome sequencing is performed on male individuals with developmental delay with or without cardiac symptoms.", "classifications": [ { "id": "Suzuki", "label": "Group Suzuki", "parent": "Takekawa", "type": "group" }, { "id": "Takekawa", "label": "Team Takekawa", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Toshiyuki", "last_name": "Itai", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Sugie", "name": null }, { "creator_type": "author", "first_name": "Yohei", "last_name": "Nitta", "name": null }, { "creator_type": "author", "first_name": "Ryuto", "last_name": "Maki", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Yoichi", "last_name": "Shinkai", "name": null }, { "creator_type": "author", "first_name": "Yoshihiro", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Nakano", "name": null }, { "creator_type": "author", "first_name": "Kazushi", "last_name": "Ichikawa", "name": null }, { "creator_type": "author", "first_name": "Nobuhiko", "last_name": "Okamoto", "name": null }, { "creator_type": "author", "first_name": "Yasuhiro", "last_name": "Utsuno", "name": null }, { "creator_type": "author", "first_name": "Eriko", "last_name": "Koshimizu", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Fujita", "name": null }, { "creator_type": "author", "first_name": "Kohei", "last_name": "Hamanaka", "name": null }, { "creator_type": "author", "first_name": "Yuri", "last_name": "Uchiyama", "name": null }, { "creator_type": "author", "first_name": "Naomi", "last_name": "Tsuchida", "name": null }, { "creator_type": "author", "first_name": "Noriko", "last_name": "Miyake", "name": null }, { "creator_type": "author", "first_name": "Kazuharu", "last_name": "Misawa", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Mizuguchi", "name": null }, { "creator_type": "author", "first_name": "Satoko", "last_name": "Miyatake", "name": null }, { "creator_type": "author", "first_name": "Naomichi", "last_name": "Matsumoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41598-023-27770-6" }, "pmcid": { "normalized": "PMC9849200" }, "pmid": { "normalized": "36653413" } }, "mesh": [ { "descriptor": "Cardiomyopathy, Dilated", "descriptor_ui": "D002311", "major_topic": true }, { "descriptor": "DNA-Binding Proteins", "descriptor_ui": "D004268", "major_topic": true }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Heart", "descriptor_ui": "D006321", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mutation, Missense", "descriptor_ui": "D020125", "major_topic": true }, { "descriptor": "Phenotype", "descriptor_ui": "D010641", "major_topic": false }, { "descriptor": "RNA-Binding Proteins", "descriptor_ui": "D016601", "major_topic": true } ], "publication": { "conference_name": null, "date": "2023 Jan 18", "date_precision": "day", "issue": "1", "normalized_date": "2023-01-18", "pages": "975", "proceedings_title": null, "publisher": "", "title": "Scientific reports", "volume": "13", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "A novel NONO variant that causes developmental delay and cardiac phenotypes.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Endothelial cells (ECs) line blood vessels and serve as a niche for hematopoietic stem and progenitor cells (HSPCs). Recent data point to tissue-specific EC specialization as well as heterogeneity; however, it remains unclear how ECs acquire these properties. Here, by combining live-imaging-based lineage-tracing and single-cell transcriptomics in zebrafish embryos, we identify an unexpected origin for part of the vascular HSPC niche. We find that islet1 (isl1)-expressing cells are the progenitors of the venous ECs that constitute the majority of the HSPC niche. These isl1-expressing cells surprisingly originate from the endoderm and differentiate into ECs in a process dependent on Bmp-Smad signaling and subsequently requiring npas4l (cloche) function. Single-cell RNA sequencing analyses show that isl1-derived ECs express a set of genes that reflect their distinct origin. This study demonstrates that endothelial specialization in the HSPC niche is determined at least in part by the origin of the ECs.", "classifications": [ { "id": "Yamamoto", "label": "Group Yamamoto", "parent": "Toyoshima", "type": "group" }, { "id": "Toyoshima", "label": "Team Toyoshima", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Nakajima", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Ishikawa", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Ayano", "last_name": "Chiba", "name": null }, { "creator_type": "author", "first_name": "Hajime", "last_name": "Fukui", "name": null }, { "creator_type": "author", "first_name": "Keisuke", "last_name": "Sako", "name": null }, { "creator_type": "author", "first_name": "Moe", "last_name": "Fukumoto", "name": null }, { "creator_type": "author", "first_name": "Kenny", "last_name": "Mattonet", "name": null }, { "creator_type": "author", "first_name": "Hyouk-Bum", "last_name": "Kwon", "name": null }, { "creator_type": "author", "first_name": "Subhra P.", "last_name": "Hui", "name": null }, { "creator_type": "author", "first_name": "Gergana D.", "last_name": "Dobreva", "name": null }, { "creator_type": "author", "first_name": "Kazu", "last_name": "Kikuchi", "name": null }, { "creator_type": "author", "first_name": "Christian S. M.", "last_name": "Helker", "name": null }, { "creator_type": "author", "first_name": "Didier Y. R.", "last_name": "Stainier", "name": null }, { "creator_type": "author", "first_name": "Naoki", "last_name": "Mochizuki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.devcel.2022.12.013" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "36693371" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Endoderm", "descriptor_ui": "D004707", "major_topic": false }, { "descriptor": "Endothelial Cells", "descriptor_ui": "D042783", "major_topic": true }, { "descriptor": "Endothelium", "descriptor_ui": "D004727", "major_topic": false }, { "descriptor": "Hematopoietic Stem Cells", "descriptor_ui": "D006412", "major_topic": false }, { "descriptor": "Zebrafish", "descriptor_ui": "D015027", "major_topic": true } ], "publication": { "conference_name": null, "date": "2023 Jan 13", "date_precision": "day", "issue": "", "normalized_date": "2023-01-13", "pages": "S1534-5807(22)00895-4", "proceedings_title": null, "publisher": "", "title": "Developmental cell", "volume": "", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Endoderm-derived islet1-expressing cells differentiate into endothelial cells to function as the vascular HSPC niche in zebrafish.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Abnormal sulfide catabolism, especially the accumulation of hydrogen sulfide (H(2)S) during hypoxic or inflammatory stresses, is a major cause of redox imbalance-associated cardiac dysfunction. Polyhydroxynaphtoquinone echinochrome A (Ech-A), a natural pigment of marine origin found in the shells and needles of many species of sea urchins, is a potent antioxidant and inhibits acute myocardial ferroptosis after ischemia/reperfusion, but the chronic effect of Ech-A on heart failure is unknown. Reactive sulfur species (RSS), which include catenated sulfur atoms, have been revealed as true biomolecules with high redox reactivity required for intracellular energy metabolism and signal transduction. Here, we report that continuous intraperitoneal administration of Ech-A (2.0 mg/kg/day) prevents RSS catabolism-associated chronic heart failure after myocardial infarction (MI) in mice. Ech-A prevented left ventricular (LV) systolic dysfunction and structural remodeling after MI. Fluorescence imaging revealed that intracellular RSS level was reduced after MI, while H(2)S/HS(-) level was increased in LV myocardium, which was attenuated by Ech-A. This result indicates that Ech-A suppresses RSS catabolism to H(2)S/HS(-) in LV myocardium after MI. In addition, Ech-A reduced oxidative stress formation by MI. Ech-A suppressed RSS catabolism caused by hypoxia in neonatal rat cardiomyocytes and human iPS cell-derived cardiomyocytes. Ech-A also suppressed RSS catabolism caused by lipopolysaccharide stimulation in macrophages. Thus, Ech-A has the potential to improve chronic heart failure after MI, in part by preventing sulfide catabolism.", "classifications": [ { "id": "JPMJCR2024", "label": "JPMJCR2024", "researcher": "Motohiro Nishida", "type": "grant" }, { "id": "Akaike", "label": "Group Akaike", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Group Nishida", "parent": "Nishida", "type": "group" }, { "id": "Nishimura", "label": "Group Nishimura", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Xiaokang", "last_name": "Tang", "name": null }, { "creator_type": "author", "first_name": "Akiyuki", "last_name": "Nishimura", "name": null }, { "creator_type": "author", "first_name": "Kohei", "last_name": "Ariyoshi", "name": null }, { "creator_type": "author", "first_name": "Kazuhiro", "last_name": "Nishiyama", "name": null }, { "creator_type": "author", "first_name": "Yuri", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Elena A.", "last_name": "Vasileva", "name": null }, { "creator_type": "author", "first_name": "Natalia P.", "last_name": "Mishchenko", "name": null }, { "creator_type": "author", "first_name": "Sergey A.", "last_name": "Fedoreyev", "name": null }, { "creator_type": "author", "first_name": "Valentin A.", "last_name": "Stonik", "name": null }, { "creator_type": "author", "first_name": "Hyoung-Kyu", "last_name": "Kim", "name": null }, { "creator_type": "author", "first_name": "Jin", "last_name": "Han", "name": null }, { "creator_type": "author", "first_name": "Yasunari", "last_name": "Kanda", "name": null }, { "creator_type": "author", "first_name": "Keitaro", "last_name": "Umezawa", "name": null }, { "creator_type": "author", "first_name": "Yasuteru", "last_name": "Urano", "name": null }, { "creator_type": "author", "first_name": "Takaaki", "last_name": "Akaike", "name": null }, { "creator_type": "author", "first_name": "Motohiro", "last_name": "Nishida", "name": null } ], "identifiers": { "doi": { "normalized": "10.3390/md21010052" }, "pmcid": { "normalized": "PMC9863521" }, "pmid": { "normalized": "36662225" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Heart Failure", "descriptor_ui": "D006333", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Myocardial Infarction", "descriptor_ui": "D009203", "major_topic": true }, { "descriptor": "Myocardium", "descriptor_ui": "D009206", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Sulfides", "descriptor_ui": "D013440", "major_topic": false }, { "descriptor": "Sulfur", "descriptor_ui": "D013455", "major_topic": false }, { "descriptor": "Ventricular Dysfunction, Left", "descriptor_ui": "D018487", "major_topic": true } ], "publication": { "conference_name": null, "date": "2023 Jan 12", "date_precision": "day", "issue": "1", "normalized_date": "2023-01-12", "pages": "", "proceedings_title": null, "publisher": "", "title": "Marine drugs", "volume": "21", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Echinochrome Prevents Sulfide Catabolism-Associated Chronic Heart Failure after Myocardial Infarction in Mice.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Metal-organic frameworks (MOFs) have attracted significant attention over the past 2 decades due to their wide applicability as functional materials. However, targeted synthesis of novel MOFs remains problematic as their formation mechanisms are poorly understood, which forces us to rely on serendipity in the synthesis of novel MOFs. Here, we demonstrate a workflow employing the artificial force induced reaction (AFIR) method to investigate the self-assembly process of the node of the SIFSIX-3-Zn MOF, [Zn(pyz)(4)(SiF(6))(2)](2-) (pyz = pyrazine), in an automated manner. The workflow encompassing AFIR calculations, generation of extensive reaction path networks, propagation simulations of intermediates, and further refinements of identified formation pathways showed that the nodal structure can form through multiple competing pathways involving interconvertible intermediates. This finding provides a plausible rationale for the stochastic multistage processes believed to be key in MOF formation. Furthermore, this work represents the first application of an automated reaction mechanism discovery method to a MOF system using a general workflow that is applicable to study the formation of other MOF motifs as well.", "classifications": [ { "id": "Hijikata", "label": "Group Hijikata", "parent": "Tsuchiya", "type": "group" }, { "id": "Tsuchiya", "label": "Team Tsuchiya", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Bastian Bjerkem", "last_name": "Skjelstad", "name": null }, { "creator_type": "author", "first_name": "Yuh", "last_name": "Hijikata", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Maeda", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/acs.inorgchem.2c03681" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "36626658" } }, "mesh": [ { "descriptor": "Metal-Organic Frameworks", "descriptor_ui": "D000073396", "major_topic": true }, { "descriptor": "Metals", "descriptor_ui": "D008670", "major_topic": false }, { "descriptor": "Pyrazines", "descriptor_ui": "D011719", "major_topic": false }, { "descriptor": "Zinc", "descriptor_ui": "D015032", "major_topic": false } ], "publication": { "conference_name": null, "date": "2023 Jan 10", "date_precision": "day", "issue": "", "normalized_date": "2023-01-10", "pages": "", "proceedings_title": null, "publisher": "", "title": "Inorganic chemistry", "volume": "", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Early-Stage Formation of the SIFSIX-3-Zn Metal-Organic Framework: An Automated Computational Study.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Lateral roots are important for a wide range of processes, including water and nutrients uptake. The CLAVATA3 (CLV3)/EMBRYO SURROUNDING REGION-RELATED (CLE) 1~7 peptide family and their cognate receptor CLV1 have been shown to negatively regulate lateral root formation under low nitrate conditions. However, little is known about how CLE signaling regulates lateral root formation. A persistent obstacle in CLE peptide research is their functional redundancies, which makes functional analyses difficult. To address this problem, we generate the cle1~7 septuple mutant (cle1~7-cr1, cr stands for mutant allele generated with CRISPR/Cas9). cle1~7-cr1 exhibits longer lateral roots under normal condition. Specifically, in cle1~7-cr1, the lateral root density is increased, and lateral root primordia initiation is found to be accelerated. Further analysis shows that cle3 single mutant exhibits slightly longer lateral roots. On the other hand, plants that overexpress CLE2 and CLE3 exhibit decreased lateral root lengths. To explore cognate receptor(s) of CLE2 and CLE3, we analyze lateral root lengths in clv1 bam1 (barely any meristem 1) double mutant. Mutating both the CLV1 and BAM1 causes longer lateral roots, but not in each single mutant. In addition, genetic analysis reveals that CLV1 and BAM1 are epistatic to CLE2 and CLE3. Furthermore, gene expression analysis shows that the LATERAL ORGAN BOUNDARIES DOMAIN/ASYMMETRIC LEAVES2-LIKE (LBD/ASL) genes, which promote lateral root formation, are upregulated in cle1~7-cr1 and clv1 bam1. We therefore propose that CLE2 and CLE3 peptides are perceived by CLV1 and BAM1 to mediate lateral root formation through LBDs regulation.", "classifications": [ { "id": "Sato", "label": "Group Sato", "parent": "Tsuchiya", "type": "group" }, { "id": "Tsuchiya", "label": "Team Tsuchiya", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Satoru", "last_name": "Nakagami", "name": null }, { "creator_type": "author", "first_name": "Tsuyoshi", "last_name": "Aoyama", "name": null }, { "creator_type": "author", "first_name": "Yoshikatsu", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Taiki", "last_name": "Kajiwara", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Ishida", "name": null }, { "creator_type": "author", "first_name": "Shinichiro", "last_name": "Sawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/tpj.16103" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "36628476" } }, "mesh": [ { "descriptor": "Arabidopsis", "descriptor_ui": "D017360", "major_topic": true }, { "descriptor": "Arabidopsis Proteins", "descriptor_ui": "D029681", "major_topic": true }, { "descriptor": "Gene Expression Regulation, Plant", "descriptor_ui": "D018506", "major_topic": false }, { "descriptor": "Intercellular Signaling Peptides and Proteins", "descriptor_ui": "D036341", "major_topic": false }, { "descriptor": "Peptides", "descriptor_ui": "D010455", "major_topic": false }, { "descriptor": "Plant Roots", "descriptor_ui": "D018517", "major_topic": true }, { "descriptor": "Protein Serine-Threonine Kinases", "descriptor_ui": "D017346", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false } ], "publication": { "conference_name": null, "date": "2023 Jan 10", "date_precision": "day", "issue": "", "normalized_date": "2023-01-10", "pages": "", "proceedings_title": null, "publisher": "", "title": "The Plant journal : for cell and molecular biology", "volume": "", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "CLE3 and its homologues share overlapping functions in the modulation of lateral root formation through CLV1 and BAM1 in Arabidopsis thaliana.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Neurotrophic tyrosine receptor kinase (NTRK) fusions define infantile fibrosarcomas in young children and NTRK-rearranged spindle-cell tumors in older children and adults, which share characteristic spindle-cell histology and CD34 or S100 protein expression. Similar phenotypes were identified in tumors with BRAF, RAF1, or RET fusions, suggesting a unifying concept of \"spindle-cell tumors with kinase gene fusions.\" In this study, we investigated CD30 expression in 38 mesenchymal tumors with kinase gene fusions using immunohistochemistry. CD30 was expressed in 15 of 22 NTRK-rearranged tumors and 12 of 16 tumors with BRAF, RAF1, or RET fusions. In total, CD30 was expressed in 27 of the 38 tumors (71%), with >50% CD30-positive cells in 21 tumors and predominantly moderate or strong staining in 24 tumors. CD34 and S100 protein were also expressed in 71% and 69% of the tumors, respectively. In contrast, CD30 was significantly less frequently expressed in other mesenchymal tumor types that histologically mimic kinase fusion-positive tumors (9 of 150 tumors, 6%), of which none showed >50% or predominantly strong staining. Among these mimicking tumors, malignant peripheral nerve sheath tumors occasionally (30%) expressed CD30, albeit in a weak focal manner in most positive cases. CD30 was also expressed in 3 of 15 separately analyzed ALK- or ROS1-positive inflammatory myofibroblastic tumors. Frequent expression of CD30 enhances the shared phenotype of spindle-cell tumors with NTRK and other kinase gene fusions, and its sensitivity seems similar to that of CD34 and S100 protein. Although moderate sensitivity hampers its use as a screening tool, CD30 expression could be valuable to rapidly identify high-yield candidates for molecular workup, particularly in communities that lack routine genetic analysis and/or for tumors with BRAF, RAF1, or RET fusions.", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Naoki", "last_name": "Kojima", "name": null }, { "creator_type": "author", "first_name": "Taisuke", "last_name": "Mori", "name": null }, { "creator_type": "author", "first_name": "Toru", "last_name": "Motoi", "name": null }, { "creator_type": "author", "first_name": "Eisuke", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Masayuki", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Ichikawa", "name": null }, { "creator_type": "author", "first_name": "Akira", "last_name": "Kawai", "name": null }, { "creator_type": "author", "first_name": "Kan", "last_name": "Yonemori", "name": null }, { "creator_type": "author", "first_name": "Cristina R.", "last_name": "Antonescu", "name": null }, { "creator_type": "author", "first_name": "Akihiko", "last_name": "Yoshida", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.modpat.2022.100083" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "36788089" } }, "mesh": [ { "descriptor": "Antigens, CD", "descriptor_ui": "D015703", "major_topic": false }, { "descriptor": "Fibrosarcoma", "descriptor_ui": "D005354", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Oncogene Proteins, Fusion", "descriptor_ui": "D015514", "major_topic": false }, { "descriptor": "Protein-Tyrosine Kinases", "descriptor_ui": "D011505", "major_topic": false }, { "descriptor": "Proto-Oncogene Proteins", "descriptor_ui": "D011518", "major_topic": false }, { "descriptor": "Proto-Oncogene Proteins B-raf", "descriptor_ui": "D048493", "major_topic": true }, { "descriptor": "Proto-Oncogene Proteins c-ret", "descriptor_ui": "D051096", "major_topic": false }, { "descriptor": "Receptor Protein-Tyrosine Kinases", "descriptor_ui": "D020794", "major_topic": false }, { "descriptor": "Receptor, trkA", "descriptor_ui": "D020917", "major_topic": false }, { "descriptor": "S100 Proteins", "descriptor_ui": "D009418", "major_topic": false } ], "publication": { "conference_name": null, "date": "2023 Jan 10", "date_precision": "day", "issue": "4", "normalized_date": "2023-01-10", "pages": "100083", "proceedings_title": null, "publisher": "", "title": "Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc", "volume": "36", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Frequent CD30 Expression in an Emerging Group of Mesenchymal Tumors With NTRK, BRAF, RAF1, or RET Fusions.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Drosophila is an excellent model organism for studying human neurodegenerative diseases (NDs). However, there is still almost no experimental system which could directly observe the degeneration of neurons and automatically quantify axonal degeneration. In this study, we created MeDUsA (a 'method for the quantification of degeneration using fly axons'), a standalone executable computer program based on Python that combines a pre-trained deep-learning masking tool with an axon terminal counting tool. This software automatically quantifies the number of retinal R7 axons in Drosophila from a confocal z-stack image series. Using this software, we were able to directly demonstrate that axons were degenerated by the representative causative genes of NDs for the first time in Drosophila. The fly retinal axon is an excellent experimental system that is capable of mimicking the pathology of axonal degeneration in human NDs. MeDUsA rapidly and accurately quantifies axons in Drosophila photoreceptor neurons. It enables large-scale research into axonal degeneration, including screening to identify genes or drugs that mediate axonal toxicity caused by ND proteins and diagnose the pathological significance of novel variants of human genes in axons.", "classifications": [ { "id": "Suzuki", "label": "Group Suzuki", "parent": "Takekawa", "type": "group" }, { "id": "Takekawa", "label": "Team Takekawa", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yohei", "last_name": "Nitta", "name": null }, { "creator_type": "author", "first_name": "Hiroki", "last_name": "Kawai", "name": null }, { "creator_type": "author", "first_name": "Ryuto", "last_name": "Maki", "name": null }, { "creator_type": "author", "first_name": "Jiro", "last_name": "Osaka", "name": null }, { "creator_type": "author", "first_name": "Satoko", "last_name": "Hakeda-Suzuki", "name": null }, { "creator_type": "author", "first_name": "Yoshitaka", "last_name": "Nagai", "name": null }, { "creator_type": "author", "first_name": "Karolina", "last_name": "Doubkova", "name": null }, { "creator_type": "author", "first_name": "Tomoko", "last_name": "Uehara", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Kenjiro", "last_name": "Kosaki", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Gaia", "last_name": "Tavosanis", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Sugie", "name": null } ], "identifiers": { "doi": { "normalized": "10.1093/hmg/ddac307" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "36611008" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Axons", "descriptor_ui": "D001369", "major_topic": false }, { "descriptor": "Drosophila", "descriptor_ui": "D004330", "major_topic": false }, { "descriptor": "Drosophila Proteins", "descriptor_ui": "D029721", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Neurodegenerative Diseases", "descriptor_ui": "D019636", "major_topic": true }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false } ], "publication": { "conference_name": null, "date": "2023 Jan 5", "date_precision": "day", "issue": "", "normalized_date": "2023-01-05", "pages": "ddac307", "proceedings_title": null, "publisher": "", "title": "Human molecular genetics", "volume": "", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Direct evaluation of neuroaxonal degeneration with the causative genes of neurodegenerative diseases in drosophila using the automated axon quantification system, MeDUsA.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Although irreversible cardiomyocyte injury provokes intracellular Ca2+ ([Ca2+]i) overload, the underlying dynamics of this response and its effects on cellular morphology remain unknown. We therefore visualised rapid-scanning confocal fluo4-[Ca2+]i dynamics and morphology of cardiomyocytes in Langendorff-perfused rat hearts following saponin-membrane permeabilisation. Our data demonstrate that 0.4% saponin-treated myocytes immediately exhibited high-frequency Ca2+ waves (131.3 waves/min/cell) with asynchronous, oscillatory contractions having a mean propagation velocity of 117.8 μm/s. These waves slowly decreased in frequency, developed a prolonged decay phase, and disappeared in 10 min resulting in high-static, fluo4-fluorescence intensity. The myocytes showing these waves displayed contraction bands, i.e., band-like actin-fibre aggregates with disruption of sarcomeric α-actinin. The contraction bands were not attenuated by the abolition of Ca2+ waves under pretreatment with ryanodine plus thapsigargin, but were partially attenuated by the calpain inhibitor MDL28170, while mechanical arrest of the myocytes by 2,3-butanedione monoxime completely attenuated contraction-band formation. The depletion of adenosine 5'-triphosphate by the mitochondrial electron uncoupler carbonyl cyanide 4-trifluoromethoxy phenylhydrazone also attenuated Ca2+ waves and contraction bands. Overall, saponin-induced myocyte [Ca2+]i overload provokes agonal Ca2+ waves and contraction bands. Contraction bands are not the direct consequence of the waves but are caused by cross-bridge interactions of the myocytes under calpain-mediated proteolysis.", "classifications": [ { "id": "JPMJCR1925", "label": "JPMJCR1925", "researcher": "Katsumasa Fujita", "type": "grant" }, { "id": "Fujita", "label": "Group Fujita", "parent": "Fujita", "type": "group" }, { "id": "Tanaka", "label": "Group Tanaka", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yuma", "last_name": "Morishita", "name": null }, { "creator_type": "author", "first_name": "Shoko", "last_name": "Tamura", "name": null }, { "creator_type": "author", "first_name": "Kentaro", "last_name": "Mochizuki", "name": null }, { "creator_type": "author", "first_name": "Yoshinori", "last_name": "Harada", "name": null }, { "creator_type": "author", "first_name": "Tetsuro", "last_name": "Takamatsu", "name": null }, { "creator_type": "author", "first_name": "Hajime", "last_name": "Hosoi", "name": null }, { "creator_type": "author", "first_name": "Hideo", "last_name": "Tanaka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41598-023-27807-w" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "36646772" } }, "mesh": [ { "descriptor": "Adenosine Triphosphate", "descriptor_ui": "D000255", "major_topic": true }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Calcium", "descriptor_ui": "D002118", "major_topic": false }, { "descriptor": "Mitochondria", "descriptor_ui": "D008928", "major_topic": false }, { "descriptor": "Myocardial Contraction", "descriptor_ui": "D009200", "major_topic": false }, { "descriptor": "Myocytes, Cardiac", "descriptor_ui": "D032383", "major_topic": true }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Sarcomeres", "descriptor_ui": "D012518", "major_topic": false } ], "publication": { "conference_name": null, "date": "2023-01", "date_precision": "month", "issue": "1", "normalized_date": "2023-01", "pages": "803", "proceedings_title": null, "publisher": "", "title": "Scientific Reports", "volume": "13", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Generation of myocyte agonal Ca2+ waves and contraction bands in perfused rat hearts following irreversible membrane permeabilisation", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Cancer cachexia is a complex metabolic disorder accounting for ~20% of cancer-related deaths, yet its metabolic landscape remains unexplored. Here, we report a decrease in B vitamin-related liver enzymes as a hallmark of systemic metabolic changes occurring in cancer cachexia. Metabolomics of multiple mouse models highlights cachexia-associated reductions of niacin, vitamin B6, and a glycine-related subset of one-carbon (C1) metabolites in the liver. Integration of proteomics and metabolomics reveals that liver enzymes related to niacin, vitamin B6, and glycine-related C1 enzymes dependent on B vitamins decrease linearly with their associated metabolites, likely reflecting stoichiometric cofactor-enzyme interactions. The decrease of B vitamin-related enzymes is also found to depend on protein abundance and cofactor subtype. These metabolic/proteomic changes and decreased protein malonylation, another cachexia feature identified by protein post-translational modification analysis, are reflected in blood samples from mouse models and gastric cancer patients with cachexia, underscoring the clinical relevance of our findings.", "classifications": [ { "id": "JPMJCR2123", "label": "JPMJCR2123", "researcher": "Shinya Kuroda", "type": "grant" }, { "id": "Kuroda", "label": "Group Kuroda", "parent": "Kuroda", "type": "group" }, { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yasushi", "last_name": "Kojima", "name": null }, { "creator_type": "author", "first_name": "Emi", "last_name": "Mishiro-Sato", "name": null }, { "creator_type": "author", "first_name": "Teruaki", "last_name": "Fujishita", "name": null }, { "creator_type": "author", "first_name": "Kiyotoshi", "last_name": "Satoh", "name": null }, { "creator_type": "author", "first_name": "Rie", "last_name": "Kajino-Sakamoto", "name": null }, { "creator_type": "author", "first_name": "Isao", "last_name": "Oze", "name": null }, { "creator_type": "author", "first_name": "Kazuki", "last_name": "Nozawa", "name": null }, { "creator_type": "author", "first_name": "Yukiya", "last_name": "Narita", "name": null }, { "creator_type": "author", "first_name": "Takatsugu", "last_name": "Ogata", "name": null }, { "creator_type": "author", "first_name": "Keitaro", "last_name": "Matsuo", "name": null }, { "creator_type": "author", "first_name": "Kei", "last_name": "Muro", "name": null }, { "creator_type": "author", "first_name": "Makoto Mark", "last_name": "Taketo", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Aoki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41467-023-41952-w" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "37803016" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cachexia", "descriptor_ui": "D002100", "major_topic": false }, { "descriptor": "Glycine", "descriptor_ui": "D005998", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Liver", "descriptor_ui": "D008099", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Niacin", "descriptor_ui": "D009525", "major_topic": true }, { "descriptor": "Proteomics", "descriptor_ui": "D040901", "major_topic": false }, { "descriptor": "Pyridoxine", "descriptor_ui": "D011736", "major_topic": false }, { "descriptor": "Stomach Neoplasms", "descriptor_ui": "D013274", "major_topic": true }, { "descriptor": "Vitamin B 6", "descriptor_ui": "D025101", "major_topic": false }, { "descriptor": "Vitamin B Complex", "descriptor_ui": "D014803", "major_topic": true } ], "publication": { "conference_name": null, "date": "2023", "date_precision": "year", "issue": "", "normalized_date": "2023", "pages": "", "proceedings_title": null, "publisher": "", "title": "Nature Communications", "volume": "14", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Decreased liver B vitamin-related enzymes as a metabolic hallmark of cancer cachexia.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The invariant cell lineage of Caenorhabditis elegans allows unambiguous assignment of the identity for each cell, which offers a unique opportunity to study developmental dynamics such as the timing of cell division, dynamics of gene expression, and cell fate decisions at single-cell resolution. However, little is known about cell morphodynamics, including the extent to which they are variable between individuals, mainly due to the lack of sufficient amount and quality of quantified data. In this study, we systematically quantified the cell morphodynamics in 52 C. elegans embryos from the two-cell stage to mid-gastrulation at the high spatiotemporal resolution, 0.5 mum thickness of optical sections, and 30-second intervals of recordings. Our data allowed systematic analyses of the morphological features. We analyzed sphericity dynamics and found a significant increase at the end of metaphase in every cell, indicating the universality of the mitotic cell rounding. Concomitant with the rounding, the volume also increased in most but not all cells, suggesting less universality of the mitotic swelling. Combining all features showed that cell morphodynamics was unique for each cell type. The cells before the onset of gastrulation could be distinguished from all the other cell types. Quantification of reproducibility in cell-cell contact revealed that variability in division timings and cell arrangements produced variability in contacts between the embryos. However, the area of such contacts occupied less than 5% of the total area, suggesting the high reproducibility of spatial occupancies and adjacency relationships of the cells. By comparing the morphodynamics of identical cells between the embryos, we observed diversity in the variability between cells and found it was determined by multiple factors, including cell lineage, cell generation, and cell-cell contact. We compared the variabilities of cell morphodynamics and cell-cell contacts with those in ascidian Phallusia mammillata embryos. The variabilities were larger in C. elegans, despite smaller differences in embryo size and number of cells at each developmental stage.", "classifications": [ { "id": "Onami", "label": "Group Onami", "parent": "Fujiwara", "type": "group" }, { "id": "Fujiwara", "label": "Team Fujiwara", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yusuke", "last_name": "Azuma", "name": null }, { "creator_type": "author", "first_name": "Hatsumi", "last_name": "Okada", "name": null }, { "creator_type": "author", "first_name": "Shuichi", "last_name": "Onami", "name": null } ], "identifiers": { "doi": { "normalized": "10.3389/fbinf.2023.1082531" }, "pmcid": { "normalized": "PMC10070942" }, "pmid": { "normalized": "37026092" } }, "mesh": [], "publication": { "conference_name": null, "date": "2023", "date_precision": "year", "issue": "", "normalized_date": "2023", "pages": "1082531", "proceedings_title": null, "publisher": "", "title": "Frontiers in bioinformatics", "volume": "3", "year": 2023 }, "ssbd": { "database": [], "repository": [ "ssbd-repos-000236" ] }, "title": "Systematic analysis of cell morphodynamics in C. elegans early embryogenesis.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Microfluidic devices offer precise control of single cells and molecules by liquid flows, downsizing tools to allow us to perform single-cell assays at unprecedented resolutions and minimizing contamination. In this chapter, we introduce an approach, called single-cell integrated nuclear and cytoplasmic RNA-sequencing (SINC-seq), which enables precise fractionation of cytoplasmic and nuclear RNA of single cells. This approach uses electric field control in microfluidics to manipulate single cells and RNA sequencing to dissect gene expression and RNA localization in subcellular compartments. The microfluidic system for SINC-seq exploits a hydrodynamic trap (a constriction in a microchannel) to isolate a single cell, selectively lyses its plasma membrane via a focused electric field, and retains the nucleus at the hydrodynamic trap during the electrophoretic extraction of cytoplasmic RNA. Here, we provide a step-by-step protocol from microfluidic RNA fractionation to off-chip preparation of RNA-sequencing libraries for full-length cDNA sequencing using both a short-read sequencer (Illumina) and a long-read sequencer (Oxford Nanopore Technologies).", "classifications": [ { "id": "Shintaku", "label": "Group Shintaku", "parent": "Shintaku", "type": "group" }, { "id": "Shintaku", "label": "Team Shintaku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Mahmoud N.", "last_name": "Abdelmoez", "name": null }, { "creator_type": "author", "first_name": "Hirofumi", "last_name": "Shintaku", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/978-1-0716-3323-6_14" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "37430055" } }, "mesh": [ { "descriptor": "Biological Assay", "descriptor_ui": "D001681", "major_topic": true }, { "descriptor": "Cytoplasm", "descriptor_ui": "D003593", "major_topic": false }, { "descriptor": "Cytosol", "descriptor_ui": "D003600", "major_topic": false }, { "descriptor": "Gene Expression", "descriptor_ui": "D015870", "major_topic": false }, { "descriptor": "Silanes", "descriptor_ui": "D012821", "major_topic": false } ], "publication": { "conference_name": null, "date": "2023", "date_precision": "year", "issue": "", "normalized_date": "2023", "pages": "179-189", "proceedings_title": null, "publisher": "", "title": "Methods in molecular biology (Clifton, N.J.)", "volume": "2689", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "A SINC-Seq Protocol for the Analysis of Subcellular Gene Expression in Single Cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Supersulphides are inorganic and organic sulphides with sulphur catenation with diverse physiological functions. Their synthesis is mainly mediated by mitochondrial cysteinyl-tRNA synthetase (CARS2) that functions as a principal cysteine persulphide synthase (CPERS). Here, we identify protective functions of supersulphides in viral airway infections (influenza and COVID-19), in aged lungs and in chronic lung diseases, including chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis (IPF). We develop a method for breath supersulphur-omics and demonstrate that levels of exhaled supersulphides increase in people with COVID-19 infection and in a hamster model of SARS-CoV-2 infection. Lung damage and subsequent lethality that result from oxidative stress and inflammation in mouse models of COPD, IPF, and ageing were mitigated by endogenous supersulphides production by CARS2/CPERS or exogenous administration of the supersulphide donor glutathione trisulphide. We revealed a protective role of supersulphides in airways with various viral or chronic insults and demonstrated the potential of targeting supersulphides in lung disease.", "classifications": [ { "id": "JPMJCR2024", "label": "JPMJCR2024", "researcher": "Motohiro Nishida", "type": "grant" }, { "id": "Akaike", "label": "Group Akaike", "parent": "Nishida", "type": "group" }, { "id": "Nakabayashi", "label": "Group Nakabayashi", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Group Nishida", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Tetsuro", "last_name": "Matsunaga", "name": null }, { "creator_type": "author", "first_name": "Hirohito", "last_name": "Sano", "name": null }, { "creator_type": "author", "first_name": "Katsuya", "last_name": "Takita", "name": null }, { "creator_type": "author", "first_name": "Masanobu", "last_name": "Morita", "name": null }, { "creator_type": "author", "first_name": "Shun", "last_name": "Yamanaka", "name": null }, { "creator_type": "author", "first_name": "Tomohiro", "last_name": "Ichikawa", "name": null }, { "creator_type": "author", "first_name": "Tadahisa", "last_name": "Numakura", "name": null }, { "creator_type": "author", "first_name": "Tomoaki", "last_name": "Ida", "name": null }, { "creator_type": "author", "first_name": "Minkyung", "last_name": "Jung", "name": null }, { "creator_type": "author", "first_name": "Seiryo", "last_name": "Ogata", "name": null }, { "creator_type": "author", "first_name": "Sunghyeon", "last_name": "Yoon", "name": null }, { "creator_type": "author", "first_name": "Naoya", "last_name": "Fujino", "name": null }, { "creator_type": "author", "first_name": "Yorihiko", "last_name": "Kyogoku", "name": null }, { "creator_type": "author", "first_name": "Yusaku", "last_name": "Sasaki", "name": null }, { "creator_type": "author", "first_name": "Akira", "last_name": "Koarai", "name": null }, { "creator_type": "author", "first_name": "Tsutomu", "last_name": "Tamada", "name": null }, { "creator_type": "author", "first_name": "Atsuhiko", "last_name": "Toyama", "name": null }, { "creator_type": "author", "first_name": "Takakazu", "last_name": "Nakabayashi", "name": null }, { "creator_type": "author", "first_name": "Lisa", "last_name": "Kageyama", "name": null }, { "creator_type": "author", "first_name": "Shigeru", "last_name": "Kyuwa", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Inaba", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Péter", "last_name": "Nagy", "name": null }, { "creator_type": "author", "first_name": "Tomohiro", "last_name": "Sawa", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Oshiumi", "name": null }, { "creator_type": "author", "first_name": "Masakazu", "last_name": "Ichinose", "name": null }, { "creator_type": "author", "first_name": "Mitsuhiro", "last_name": "Yamada", "name": null }, { "creator_type": "author", "first_name": "Hisatoshi", "last_name": "Sugiura", "name": null }, { "creator_type": "author", "first_name": "Fan-Yan", "last_name": "Wei", "name": null }, { "creator_type": "author", "first_name": "Hozumi", "last_name": "Motohashi", "name": null }, { "creator_type": "author", "first_name": "Takaaki", "last_name": "Akaike", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41467-023-40182-4" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "37491435" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "COVID-19", "descriptor_ui": "D000086382", "major_topic": true }, { "descriptor": "Idiopathic Pulmonary Fibrosis", "descriptor_ui": "D054990", "major_topic": true }, { "descriptor": "Lung", "descriptor_ui": "D008168", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Pulmonary Disease, Chronic Obstructive", "descriptor_ui": "D029424", "major_topic": true }, { "descriptor": "SARS-CoV-2", "descriptor_ui": "D000086402", "major_topic": false } ], "publication": { "conference_name": null, "date": "2023", "date_precision": "year", "issue": "", "normalized_date": "2023", "pages": "", "proceedings_title": null, "publisher": "", "title": "Nature Communications", "volume": "14", "year": 2023 }, "ssbd": { "database": [], "repository": [ "ssbd-repos-000426" ] }, "title": "Supersulphides provide airway protection in viral and chronic lung diseases.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Building limb morphogenesis in vitro would substantially open up avenues for research and applications of appendage development. Recently, advances in stem cell engineering to differentiate desired cell types and produce multicellular structures in vitro have enabled the derivation of limb-like tissues from pluripotent stem cells. However, in vitro recapitulation of limb morphogenesis is yet to be achieved. To formulate a method of building limbs in vitro, it is critically important to understand developmental mechanisms, especially the modularity and the dependency of limb development on the external tissues, as those would help us to postulate what can be self-organized and what needs to be externally manipulated when reconstructing limb development in vitro. Although limbs are formed on the designated limb field on the flank of embryo in the normal developmental context, limbs can also be regenerated on the amputated stump in some animals and experimentally induced at ectopic locations, which highlights the modular aspects of limb morphogenesis. The forelimb-hindlimb identity and the dorsal-ventral, proximal-distal, and anterior-posterior axes are initially instructed by the body axis of the embryo, and maintained in the limb domain once established. In contrast, the aspects of dependency on the external tissues are especially underscored by the contribution of incoming tissues, such as muscles, blood vessels, and peripheral nerves, to developing limbs. Together, those developmental mechanisms explain how limb-like tissues could be derived from pluripotent stem cells. Prospectively, the higher complexity of limb morphologies is expected to be recapitulated by introducing the morphogen gradient and the incoming tissues in the culture environment. Those technological developments would dramatically enhance experimental accessibility and manipulability for elucidating the mechanisms of limb morphogenesis and interspecies differences. Furthermore, if human limb development can be modeled, drug development would be benefited by in vitro assessment of prenatal toxicity on congenital limb deficiencies. Ultimately, we might even create a future in which the lost appendage would be recovered by transplanting artificially grown human limbs.", "classifications": [ { "id": "JPMJCR1922", "label": "JPMJCR1922", "researcher": "Mototsugu Eiraku", "type": "grant" }, { "id": "Eiraku", "label": "Group Eiraku", "parent": "Eiraku", "type": "group" }, { "id": "Eiraku", "label": "Team Eiraku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Rio", "last_name": "Tsutsumi", "name": null }, { "creator_type": "author", "first_name": "Mototsugu", "last_name": "Eiraku", "name": null } ], "identifiers": { "doi": { "normalized": "10.3389/fcell.2023.1135784" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "37283945" } }, "mesh": [], "publication": { "conference_name": null, "date": "2023", "date_precision": "year", "issue": "", "normalized_date": "2023", "pages": "", "proceedings_title": null, "publisher": "", "title": "Frontiers in Cell and Developmental Biology", "volume": "11", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "How might we build limbs in vitro informed by the modular aspects and tissue-dependency in limb development?", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "A principal concept in developing antibacterial agents with selective toxicity is blocking metabolic pathways that are critical for bacterial growth but that mammalian cells lack. Serine O-acetyltransferase (CysE) is an enzyme in many bacteria that catalyzes the first step in l-cysteine biosynthesis by transferring an acetyl group from acetyl coenzyme A (acetyl-CoA) to l-serine to form O-acetylserine. Because mammalian cells lack this l-cysteine biosynthesis pathway, developing an inhibitor of CysE has been thought to be a way to establish a new class of antibacterial agents. Here, we demonstrated that alkyl gallates such as octyl gallate (OGA) could act as potent CysE inhibitors in vitro and in bacteria. Mass spectrometry analyses indicated that OGA treatment markedly reduced intrabacterial levels of l-cysteine and its metabolites including glutathione and glutathione persulfide in Escherichia coli to a level similar to that found in E. coli lacking the cysE gene. Consistent with the reduction of those antioxidant molecules in bacteria, E. coli became vulnerable to hydrogen peroxide-mediated bacterial killing in the presence of OGA. More important, OGA treatment intensified susceptibilities of metallo-β-lactamase-expressing Gram-negative bacteria (E. coli and Klebsiella pneumoniae) to carbapenem. Structural analyses showed that alkyl gallate bound to the binding site for acetyl-CoA that limits access of acetyl-CoA to the active site. Our data thus suggest that CysE inhibitors may be used to treat infectious diseases caused by drug-resistant Gram-negative bacteria not only via direct antibacterial activity but also by enhancing therapeutic potentials of existing antibiotics.", "classifications": [ { "id": "JPMJCR2024", "label": "JPMJCR2024", "researcher": "Motohiro Nishida", "type": "grant" }, { "id": "Akaike", "label": "Group Akaike", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Group Nishida", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Touya", "last_name": "Toyomoto", "name": null }, { "creator_type": "author", "first_name": "Katsuhiko", "last_name": "Ono", "name": null }, { "creator_type": "author", "first_name": "Tomoo", "last_name": "Shiba", "name": null }, { "creator_type": "author", "first_name": "Kenta", "last_name": "Momitani", "name": null }, { "creator_type": "author", "first_name": "Tianli", "last_name": "Zhang", "name": null }, { "creator_type": "author", "first_name": "Hiroyasu", "last_name": "Tsutsuki", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Ishikawa", "name": null }, { "creator_type": "author", "first_name": "Kanae", "last_name": "Hoso", "name": null }, { "creator_type": "author", "first_name": "Koma", "last_name": "Hamada", "name": null }, { "creator_type": "author", "first_name": "Azizur", "last_name": "Rahman", "name": null }, { "creator_type": "author", "first_name": "Liping", "last_name": "Wen", "name": null }, { "creator_type": "author", "first_name": "Yosuke", "last_name": "Maeda", "name": null }, { "creator_type": "author", "first_name": "Keiichi", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Masao", "last_name": "Matsuoka", "name": null }, { "creator_type": "author", "first_name": "Kenjiro", "last_name": "Hanaoka", "name": null }, { "creator_type": "author", "first_name": "Takuro", "last_name": "Niidome", "name": null }, { "creator_type": "author", "first_name": "Takaaki", "last_name": "Akaike", "name": null }, { "creator_type": "author", "first_name": "Tomohiro", "last_name": "Sawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.3389/fmicb.2023.1276447" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "37965540" } }, "mesh": [], "publication": { "conference_name": null, "date": "2023", "date_precision": "year", "issue": "", "normalized_date": "2023", "pages": "", "proceedings_title": null, "publisher": "", "title": "Frontiers in Microbiology", "volume": "14", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Alkyl gallates inhibit serine O-acetyltransferase in bacteria and enhance susceptibility of drug-resistant Gram-negative bacteria to antibiotics.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Breastfeeding, which is essential for the survival of mammalian infants, is critically mediated by pulsatile secretion of the pituitary hormone oxytocin from the central oxytocin neurons located in the paraventricular and supraoptic hypothalamic nuclei of mothers. Despite its importance, the molecular and neural circuit mechanisms of the milk ejection reflex remain poorly understood, in part because a mouse model to study lactation was only recently established. In our previous study, we successfully introduced fiber photometry-based chronic imaging of the pulsatile activities of oxytocin neurons during lactation. However, the necessity of Cre recombinase-based double knock-in mice substantially compromised the use of various Cre-dependent neuroscience toolkits. To overcome this obstacle, we developed a simple Cre-free method for monitoring oxytocin neurons by an adeno-associated virus vector driving GCaMP6s under a 2.6 kb mouse oxytocin mini-promoter. Using this method, we monitored calcium ion transients of oxytocin neurons in the paraventricular nucleus in wild-type C57BL/6N and ICR mothers without genetic crossing. By combining this method with video recordings of mothers and pups, we found that the pulsatile activities of oxytocin neurons require physical mother-pup contact for the milk ejection reflex. Notably, the frequencies of photometric signals were dynamically modulated by mother-pup reunions after isolation and during natural weaning stages. Collectively, the present study illuminates the temporal dynamics of pulsatile activities of oxytocin neurons in wild-type mice and provides a tool to characterize maternal oxytocin functions.", "classifications": [ { "id": "Miyamichi", "label": "Group Miyamichi", "parent": "Enomoto", "type": "group" }, { "id": "Enomoto", "label": "Team Enomoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Kasane", "last_name": "Yaguchi", "name": null }, { "creator_type": "author", "first_name": "Mitsue", "last_name": "Hagihara", "name": null }, { "creator_type": "author", "first_name": "Ayumu", "last_name": "Konno", "name": null }, { "creator_type": "author", "first_name": "Hirokazu", "last_name": "Hirai", "name": null }, { "creator_type": "author", "first_name": "Hiroko", "last_name": "Yukinaga", "name": null }, { "creator_type": "author", "first_name": "Kazunari", "last_name": "Miyamichi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1371/journal.pone.0285589" }, "pmcid": { "normalized": "PMC10171594" }, "pmid": { "normalized": "37163565" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Lactation", "descriptor_ui": "D007774", "major_topic": true }, { "descriptor": "Mammals", "descriptor_ui": "D008322", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Inbred ICR", "descriptor_ui": "D008813", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Oxytocin", "descriptor_ui": "D010121", "major_topic": true }, { "descriptor": "Paraventricular Hypothalamic Nucleus", "descriptor_ui": "D010286", "major_topic": false }, { "descriptor": "Supraoptic Nucleus", "descriptor_ui": "D013495", "major_topic": false } ], "publication": { "conference_name": null, "date": "2023", "date_precision": "year", "issue": "5", "normalized_date": "2023", "pages": "e0285589", "proceedings_title": null, "publisher": "", "title": "PloS one", "volume": "18", "year": 2023 }, "ssbd": { "database": [], "repository": [ "ssbd-repos-000308" ] }, "title": "Dynamic modulation of pulsatile activities of oxytocin neurons in lactating wild-type mice.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Adaptability to changing environments is one of the universal characteristics of living organisms. Because individual modes of adaptation are diverse, a unified understanding of these diverse modes is essential to comprehend adaptation. Adaptations can be categorized from at least two perspectives with respect to information. One is the passivity and activity of adaptation and the other is the type of information transmission. In Darwinian natural selection, organisms are selected among randomly generated traits under which individual organisms are passive in the sense that they do not process any environmental information. On the other hand, organisms can also adapt by sensing their environment and changing their traits. This is an active adaptation in that it makes use of environmental information. In terms of information transfer, adaptation through phenotypic heterogeneity, such as bacterial bet-hedging, is intragenerational in which traits are not passed on to the next generation. In contrast, adaptation through genetic diversity is intergenerational. The theory of population dynamics enables us to unify these various modes of adaptations and their properties can be analyzed qualitatively and quantitatively using techniques from quantitative genetics and information thermodynamics. In addition, such methods can be applied to situations where organisms can learn from past experiences and pass them on from generation to generation. In this work, we introduce the unified theory of biological adaptation based on population dynamics and show its potential applications to evaluate the fitness value of information and to analyze experimental lineage tree data. Finally, we discuss future perspectives for its development. This review article is an extended version of the Japanese article in SEIBUTSU BUTSURI Vol. 57, p. 287–290 (2017).", "classifications": [ { "id": "JPMJCR1927", "label": "JPMJCR1927", "researcher": "Yuichi Wakamoto", "type": "grant" }, { "id": "Kobayashi", "label": "Group Kobayashi", "parent": "Wakamoto", "type": "group" }, { "id": "Wakamoto", "label": "Group Wakamoto", "parent": "Wakamoto", "type": "group" }, { "id": "Wakamoto", "label": "Team Wakamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "So", "last_name": "Nakashima", "name": null }, { "creator_type": "author", "first_name": "Tetsuya", "last_name": "J. Kobayashi", "name": null } ], "identifiers": { "doi": { "normalized": "10.2142/biophysico.bppb-v20.0034" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "38124797" } }, "mesh": [], "publication": { "conference_name": null, "date": "2023", "date_precision": "year", "issue": "3", "normalized_date": "2023", "pages": "", "proceedings_title": null, "publisher": "", "title": "Biophysics and Physicobiology", "volume": "20", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Population dynamics models for various forms of adaptation.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Gene deletion is one of the standard approaches in genetics to investigate the roles and functions of target genes. However, the influence of gene deletion on cellular phenotypes is usually analyzed sometime after the gene deletion was introduced. Such lags from gene deletion to phenotype evaluation could select only the fittest fraction of genedeleted cells and hinder the detection of potentially diverse phenotypic consequences. Therefore, dynamic aspects of gene deletion, such as real-time propagation and compensation of deletion effects on cellular phenotypes, still need to be explored. To resolve this issue, we have recently introduced a new method that combines a photoactivatable Cre recombination system and microfluidic single-cell observation. This method enables us to induce gene deletion at desired timings in single bacterial cells and to monitor their dynamics for prolonged periods. Here, we detail the protocol for estimating the fractions of gene-deleted cells based on a batch-culture assay. The duration of blue light exposure significantly affects the fractions of gene-deleted cells. Therefore, gene-deleted and non-deleted cells can coexist in a cellular population by adjusting the duration of blue light exposure. Single-cell observations under such illumination conditions allow the comparison of temporal dynamics between gene-deleted and non-deleted cells and unravel phenotypic dynamics provoked by gene deletion.", "classifications": [ { "id": "JPMJCR1927", "label": "JPMJCR1927", "researcher": "Yuichi Wakamoto", "type": "grant" }, { "id": "Wakamoto", "label": "Group Wakamoto", "parent": "Wakamoto", "type": "group" }, { "id": "Wakamoto", "label": "Team Wakamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yuta", "last_name": "Koganezawa", "name": null }, { "creator_type": "author", "first_name": "Yuichi", "last_name": "Wakamoto", "name": null }, { "creator_type": "author", "first_name": "Moritoshi", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Miki", "last_name": "Umetani", "name": null } ], "identifiers": { "doi": { "normalized": "10.21769/bioprotoc.4685" }, "pmcid": { "normalized": null }, "pmid": { "normalized": null } }, "mesh": [], "publication": { "conference_name": null, "date": "2023", "date_precision": "year", "issue": "11", "normalized_date": "2023", "pages": "", "proceedings_title": null, "publisher": "", "title": "BIO-PROTOCOL", "volume": "13", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Detecting Photoactivatable Cre-mediated Gene Deletion Efficiency in Escherichia coli", "url": "https://bio-protocol.org/e4685", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Amoeboid cell movement and migration are wide-spread across various cell types and species. Microscopy-based analysis of the model systems Dictyostelium and neutrophils over the years have uncovered generality in their overall cell movement pattern. Under no directional cues, the centroid movement can be quantitatively characterized by their persistence to move in a straight line and the frequency of re-orientation. Mathematically, the cells essentially behave as a persistent random walker with memory of two characteristic time-scale. Such quantitative characterization is important from a cellular-level ethology point of view as it has direct connotation to their exploratory and foraging strategies. Interestingly, outside the amoebozoa and metazoa, there are largely uncharacterized species in the excavate taxon Heterolobosea including amoeboflagellate Naegleria. While classical works have shown that these cells indeed show typical amoeboid locomotion on an attached surface, their quantitative features are so far unexplored. Here, we analyzed the cell movement of Naegleria gruberi by employing long-time phase contrast imaging that automatically tracks individual cells. We show that the cells move as a persistent random walker with two time-scales that are close to those known in Dictyostelium and neutrophils. Similarities were also found in the shape dynamics which are characterized by the appearance, splitting and annihilation of the curvature waves along the cell edge. Our analysis based on the Fourier descriptor and a neural network classifier point to importance of morphology features unique to Naegleria including complex protrusions and the transient bipolar dumbbell morphologies.", "classifications": [ { "id": "JPMJCR1923", "label": "JPMJCR1923", "researcher": "Satoshi Sawai", "type": "grant" }, { "id": "Sawai", "label": "Group Sawai", "parent": "Sawai", "type": "group" }, { "id": "Sawai", "label": "Team Sawai", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Masahito", "last_name": "Uwamichi", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Miura", "name": null }, { "creator_type": "author", "first_name": "Ayako", "last_name": "Kamiya", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Imoto", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Sawai", "name": null } ], "identifiers": { "doi": { "normalized": "10.3389/fcell.2023.1274127" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "38020930" } }, "mesh": [], "publication": { "conference_name": null, "date": "2023", "date_precision": "year", "issue": "", "normalized_date": "2023", "pages": "", "proceedings_title": null, "publisher": "", "title": "Frontiers in Cell and Developmental Biology", "volume": "11", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Random walk and cell morphology dynamics in Naegleria gruberi.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "", "classifications": [ { "id": "JPMJCR1921", "label": "JPMJCR1921", "researcher": "Itaru Imayoshi", "type": "grant" }, { "id": "Imayoshi", "label": "Group Imayoshi", "parent": "Imayoshi", "type": "group" }, { "id": "Imayoshi", "label": "Team Imayoshi", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Shinji C.", "last_name": "Nagasaki", "name": null }, { "creator_type": "author", "first_name": "Tomonori D.", "last_name": "Fukuda", "name": null }, { "creator_type": "author", "first_name": "Mayumi", "last_name": "Yamada", "name": null }, { "creator_type": "author", "first_name": "Yusuke Iii", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Ryo", "last_name": "Kakutani", "name": null }, { "creator_type": "author", "first_name": "Adam T.", "last_name": "Guy", "name": null }, { "creator_type": "author", "first_name": "Itaru", "last_name": "Imayoshi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1247/csf.22074" }, "pmcid": { "normalized": null }, "pmid": { "normalized": null } }, "mesh": [], "publication": { "conference_name": null, "date": "2023", "date_precision": "year", "issue": "1", "normalized_date": "2023", "pages": "31-47", "proceedings_title": null, "publisher": "", "title": "Cell Structure and Function", "volume": "48", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Enhancement of Vivid-based photo-activatable Gal4 transcription factor in mammalian cells", "url": "https://www.jstage.jst.go.jp/article/csf/48/1/48_22074/_article", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Hepatocellular death increases with hepatic steatosis aggravation, although its regulation remains unclear. Here we show that hepatic steatosis aggravation shifts the hepatocellular death mode from apoptosis to necroptosis, causing increased hepatocellular death. Our results reveal that the transcription factor ATF3 acts as a master regulator in this shift by inducing expression of RIPK3, a regulator of necroptosis. In severe hepatic steatosis, after partial hepatectomy, hepatic ATF3-deficient or -overexpressing mice display decreased or increased RIPK3 expression and necroptosis, respectively. In cultured hepatocytes, ATF3 changes TNFα-dependent cell death mode from apoptosis to necroptosis, as revealed by live-cell imaging. In non-alcoholic steatohepatitis (NASH) mice, hepatic ATF3 deficiency suppresses RIPK3 expression and hepatocellular death. In human NASH, hepatocellular damage is correlated with the frequency of hepatocytes expressing ATF3 or RIPK3, which overlap frequently. ATF3-dependent RIPK3 induction, causing a modal shift of hepatocellular death, can be a therapeutic target for steatosis-induced liver damage, including NASH.", "classifications": [ { "id": "JPMJCR2123", "label": "JPMJCR2123", "researcher": "Shinya Kuroda", "type": "grant" }, { "id": "Inaba", "label": "Group Inaba", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Group Kuroda", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yuka", "last_name": "Inaba", "name": null }, { "creator_type": "author", "first_name": "Emi", "last_name": "Hashiuchi", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Kumi", "last_name": "Kimura", "name": null }, { "creator_type": "author", "first_name": "Yu", "last_name": "Oshima", "name": null }, { "creator_type": "author", "first_name": "Kohsuke", "last_name": "Tsuchiya", "name": null }, { "creator_type": "author", "first_name": "Shin", "last_name": "Murai", "name": null }, { "creator_type": "author", "first_name": "Chiaki", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Michihiro", "last_name": "Matsumoto", "name": null }, { "creator_type": "author", "first_name": "Shigetaka", "last_name": "Kitajima", "name": null }, { "creator_type": "author", "first_name": "Yasuhiko", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Masao", "last_name": "Honda", "name": null }, { "creator_type": "author", "first_name": "Shun-ichiro", "last_name": "Asahara", "name": null }, { "creator_type": "author", "first_name": "Kim", "last_name": "Ravnskjaer", "name": null }, { "creator_type": "author", "first_name": "Shin-ichi", "last_name": "Horike", "name": null }, { "creator_type": "author", "first_name": "Shuichi", "last_name": "Kaneko", "name": null }, { "creator_type": "author", "first_name": "Masato", "last_name": "Kasuga", "name": null }, { "creator_type": "author", "first_name": "Hiroyasu", "last_name": "Nakano", "name": null }, { "creator_type": "author", "first_name": "Kenichi", "last_name": "Harada", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Inoue", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41467-023-35804-w" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "36690638" } }, "mesh": [ { "descriptor": "Activating Transcription Factor 3", "descriptor_ui": "D051700", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Apoptosis", "descriptor_ui": "D017209", "major_topic": false }, { "descriptor": "Cell Death", "descriptor_ui": "D016923", "major_topic": false }, { "descriptor": "Hepatocytes", "descriptor_ui": "D022781", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Necroptosis", "descriptor_ui": "D000079302", "major_topic": false }, { "descriptor": "Non-alcoholic Fatty Liver Disease", "descriptor_ui": "D065626", "major_topic": true }, { "descriptor": "Receptor-Interacting Protein Serine-Threonine Kinases", "descriptor_ui": "D053422", "major_topic": false }, { "descriptor": "Transcription Factors", "descriptor_ui": "D014157", "major_topic": false } ], "publication": { "conference_name": null, "date": "2023", "date_precision": "year", "issue": "", "normalized_date": "2023", "pages": "", "proceedings_title": null, "publisher": "", "title": "Nature Communications", "volume": "14", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "The transcription factor ATF3 switches cell death from apoptosis to necroptosis in hepatic steatosis in male mice.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "High-throughput omics technologies have enabled the profiling of entire biological systems. For the biological interpretation of such omics data, two analyses, hypothesis- and data-driven analyses including tensor decomposition, have been used. Both analyses have their own advantages and disadvantages and are mutually complementary; however, a direct comparison of these two analyses for omics data is poorly examined.We applied tensor decomposition (TD) to a dataset representing changes in the concentrations of 562 blood molecules at 14 time points in 20 healthy human subjects after ingestion of 75 g oral glucose. We characterized each molecule by individual dependence (constant or variable) and time dependence (later peak or early peak). Three of the four features extracted by TD were characterized by our previous hypothesis-driven study, indicating that TD can extract some of the same features obtained by hypothesis-driven analysis in a non-biased manner. In contrast to the years taken for our previous hypothesis-driven analysis, the data-driven analysis in this study took days, indicating that TD can extract biological features in a non-biased manner without the time-consuming process of hypothesis generation.", "classifications": [ { "id": "JPMJCR2123", "label": "JPMJCR2123", "researcher": "Shinya Kuroda", "type": "grant" }, { "id": "Kuroda", "label": "Group Kuroda", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Suguru", "last_name": "Fujita", "name": null }, { "creator_type": "author", "first_name": "Yasuaki", "last_name": "Karasawa", "name": null }, { "creator_type": "author", "first_name": "Ken-ichi", "last_name": "Hironaka", "name": null }, { "creator_type": "author", "first_name": "Y.-h", "last_name": "Taguchi", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Kuroda", "name": null } ], "identifiers": { "doi": { "normalized": "10.1371/journal.pone.0281594" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "36791130" } }, "mesh": [ { "descriptor": "Blood", "descriptor_ui": "D001769", "major_topic": true }, { "descriptor": "Blood Chemical Analysis", "descriptor_ui": "D001774", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Metabolome", "descriptor_ui": "D055442", "major_topic": true } ], "publication": { "conference_name": null, "date": "2023", "date_precision": "year", "issue": "2", "normalized_date": "2023", "pages": "", "proceedings_title": null, "publisher": "", "title": "PLOS ONE", "volume": "18", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Features extracted using tensor decomposition reflect the biological features of the temporal patterns of human blood multimodal metabolome.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The outbreak-causing monkeypox virus of 2022 (2022 MPXV) is classified as a clade IIb strain and phylogenetically distinct from prior endemic MPXV strains (clades I or IIa), suggesting that its virological properties may also differ. Here, we used human keratinocytes and induced pluripotent stem cell-derived colon organoids to examine the efficiency of viral growth in these cells and the MPXV infection-mediated host responses. MPXV replication was much more productive in keratinocytes than in colon organoids. We observed that MPXV infections, regardless of strain, caused cellular dysfunction and mitochondrial damage in keratinocytes. Notably, a significant increase in the expression of hypoxia-related genes was observed specifically in 2022 MPXV-infected keratinocytes. Our comparison of virological features between 2022 MPXV and prior endemic MPXV strains revealed signaling pathways potentially involved with the cellular damages caused by MPXV infections and highlights host vulnerabilities that could be utilized as protective therapeutic strategies against human mpox in the future.", "classifications": [ { "id": "Yamamoto", "label": "Group Yamamoto", "parent": "Toyoshima", "type": "group" }, { "id": "Toyoshima", "label": "Team Toyoshima", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yukio", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Izumi", "last_name": "Kimura", "name": null }, { "creator_type": "author", "first_name": "Rina", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Ayaka", "last_name": "Sakamoto", "name": null }, { "creator_type": "author", "first_name": "Naoko", "last_name": "Yasuhara", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "The Genotype to Phenotype Japan (G2P-Japan)", "last_name": "Consortium", "name": null }, { "creator_type": "author", "first_name": "Kei", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Kazuo", "last_name": "Takayama", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/jmv.28827" }, "pmcid": { "normalized": null }, "pmid": { "normalized": null } }, "mesh": [], "publication": { "conference_name": null, "date": "2023", "date_precision": "year", "issue": "6", "normalized_date": "2023", "pages": "e28827", "proceedings_title": null, "publisher": "", "title": "Journal of Medical Virology", "volume": "95", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Virological characterization of the 2022 outbreak-causing monkeypox virus using human keratinocytes and colon organoids", "url": "https://onlinelibrary.wiley.com/doi/abs/10.1002/jmv.28827", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Sequencing technology has identified aplastic anemia (AA) not only as an autoimmune bone marrow failure syndrome, but also as a clonal hematopoietic disease. Here, we present a case in which an ASXL1-mutated clone was predominantly expanded during the treatment of AA. A 58-year-old man with chronic glomerulonephritis on maintenance hemodialysis presented with pancytopenia. The findings of bone marrow biopsy indicated a hypoplastic bone marrow. Magnetic resonant imaging showed fatty changes in the bone marrow. The patient was eventually diagnosed with severe AA. He was treated with anti-human thymocyte globulin, cyclosporine, granulocyte colony-stimulating factor, and the thrombopoietin receptor agonist (TPO-RA) eltrombopag. After switching to another TPO-RA, romiplostim, the neutrophil, reticulocyte, and platelet counts gradually improved, and blood transfusion was not needed 1 year after treatment. Mutational analyses revealed that reconstituted hematopoietic cells originated from the ASXL1-mutated clone. Nevertheless, the patient's blood cell counts remained normal 2 years after treatment.", "classifications": [ { "id": "Nishikii", "label": "Group Nishikii", "parent": "Shintaku", "type": "group" }, { "id": "Shintaku", "label": "Team Shintaku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yumoe", "last_name": "Shimizu", "name": null }, { "creator_type": "author", "first_name": "Hidekazu", "last_name": "Nishikii", "name": null }, { "creator_type": "author", "first_name": "Tadashi", "last_name": "Iitsuka", "name": null }, { "creator_type": "author", "first_name": "Ryota", "last_name": "Matsuoka", "name": null }, { "creator_type": "author", "first_name": "Naoki", "last_name": "Kurita", "name": null }, { "creator_type": "author", "first_name": "Tatsuhiro", "last_name": "Sakamoto", "name": null }, { "creator_type": "author", "first_name": "Yasuhisa", "last_name": "Yokoyama", "name": null }, { "creator_type": "author", "first_name": "Takayasu", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Yasuhito", "last_name": "Suehara", "name": null }, { "creator_type": "author", "first_name": "Keiichiro", "last_name": "Hattori", "name": null }, { "creator_type": "author", "first_name": "Yumiko", "last_name": "Maruyama", "name": null }, { "creator_type": "author", "first_name": "Yasuhito", "last_name": "Nannya", "name": null }, { "creator_type": "author", "first_name": "Seishi", "last_name": "Ogawa", "name": null }, { "creator_type": "author", "first_name": "Mamiko", "last_name": "Sakata-Yanagimoto", "name": null }, { "creator_type": "author", "first_name": "Shigeru", "last_name": "Chiba", "name": null }, { "creator_type": "author", "first_name": "Naoshi", "last_name": "Obara", "name": null } ], "identifiers": { "doi": { "normalized": "10.11406/rinketsu.64.49" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "36775307" } }, "mesh": [ { "descriptor": "Anemia, Aplastic", "descriptor_ui": "D000741", "major_topic": true }, { "descriptor": "Antilymphocyte Serum", "descriptor_ui": "D000961", "major_topic": false }, { "descriptor": "Bone Marrow", "descriptor_ui": "D001853", "major_topic": false }, { "descriptor": "Bone Marrow Failure Disorders", "descriptor_ui": "D000080983", "major_topic": false }, { "descriptor": "Clone Cells", "descriptor_ui": "D002999", "major_topic": false }, { "descriptor": "Hematopoietic Stem Cells", "descriptor_ui": "D006412", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Immunosuppression Therapy", "descriptor_ui": "D007165", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Repressor Proteins", "descriptor_ui": "D012097", "major_topic": false } ], "publication": { "conference_name": null, "date": "2023", "date_precision": "year", "issue": "1", "normalized_date": "2023", "pages": "49-53", "proceedings_title": null, "publisher": "", "title": "[Rinsho ketsueki] The Japanese journal of clinical hematology", "volume": "64", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "[Hematopoietic recovery by ASXL1-mutated clones after immune suppressive therapy in a patient with severe aplastic anemia].", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Progress of molecular biology resulted in the accumulation of information on biomolecular interactions, which are complex enough to be termed as networks. Dynamical behavior generated by complex network systems is considered to be the origin of the biological functions. One of the largest missions in modern life science is to obtain logical understanding for the dynamics of complex systems based on experimentally identified networks. However, a network does not provide sufficient information to specify dynamics explicitly, i.e. it lacks information of mathematical formulae of functions or parameter values. One has to develop mathematical models under assumptions of functions and parameter values to know the detail of dynamics of network systems. In this review, on the other hand, we introduce our own mathematical theory to understand the behavior of biological systems from the information of regulatory networks alone. Using the theory, important aspects of dynamical properties can be extracted from networks. Namely, key factors for observing/controlling the whole dynamical system are determined from network structure alone. We also show an application of the theory to a real biological system, a gene regulatory network for cell-fate specification in ascidian. We demonstrate that the system was completely controllable by experimental manipulations of the key factors identified by the theory from the information of network alone. This review article is an extended version of the Japanese article, Controlling Cell-Fate Specification System Based on a Mathematical Theory of Network Dynamics, published in SEIBUTSU BUTSURI Vol. 60, p. 349-351 (2020).", "classifications": [ { "id": "Mochizuki", "label": "Group Mochizuki", "parent": "Eiraku", "type": "group" }, { "id": "Eiraku", "label": "Team Eiraku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Atsushi", "last_name": "Mochizuki", "name": null } ], "identifiers": { "doi": { "normalized": "10.2142/biophysico.bppb-v20.0019" }, "pmcid": { "normalized": "PMC10941957" }, "pmid": { "normalized": "38496244" } }, "mesh": [], "publication": { "conference_name": null, "date": "2023", "date_precision": "year", "issue": "2", "normalized_date": "2023", "pages": "e200019", "proceedings_title": null, "publisher": "", "title": "Biophysics and physicobiology", "volume": "20", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Controlling complex dynamical systems based on the structure of the networks.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The thymus has the ability to regenerate from acute injury caused by radiation, infection, and stressors. In addition to thymocytes, thymic epithelial cells in the medulla (mTECs), which are crucial for T cell self-tolerance by ectopically expressing and presenting thousands of tissue-specific antigens (TSAs), are damaged by these insults and recover thereafter. However, given recent discoveries on the high heterogeneity of mTECs, it remains to be determined whether the frequency and properties of mTEC subsets are restored during thymic recovery from radiation damage. Here we demonstrate that acute total body irradiation with a sublethal dose induces aftereffects on heterogeneity and gene expression of mTECs. Single-cell RNA-sequencing (scRNA-seq) analysis showed that irradiation reduces the frequency of mTECs expressing AIRE, which is a critical regulator of TSA expression, 15 days after irradiation. In contrast, transit-amplifying mTECs (TA-mTECs), which are progenitors of AIRE-expressing mTECs, and Ccl21a-expressing mTECs, were less affected. Interestingly, a detailed analysis of scRNA-seq data suggested that the proportion of a unique mTEC cluster expressing Ccl25 and a high level of TSAs was severely decreased by irradiation. In sum, we propose that the effects of acute irradiation disrupt the heterogeneity and properties of mTECs over an extended period, which potentially leads to an impairment of thymic T cell selection.", "classifications": [ { "id": "Kobayashi", "label": "Group Kobayashi", "parent": "Wakamoto", "type": "group" }, { "id": "Wakamoto", "label": "Team Wakamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Kenta", "last_name": "Horie", "name": null }, { "creator_type": "author", "first_name": "Kano", "last_name": "Namiki", "name": null }, { "creator_type": "author", "first_name": "Kyouhei", "last_name": "Kinoshita", "name": null }, { "creator_type": "author", "first_name": "Maki", "last_name": "Miyauchi", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Ishikawa", "name": null }, { "creator_type": "author", "first_name": "Mio", "last_name": "Hayama", "name": null }, { "creator_type": "author", "first_name": "Yuya", "last_name": "Maruyama", "name": null }, { "creator_type": "author", "first_name": "Naho", "last_name": "Hagiwara", "name": null }, { "creator_type": "author", "first_name": "Takahisa", "last_name": "Miyao", "name": null }, { "creator_type": "author", "first_name": "Shigeo", "last_name": "Murata", "name": null }, { "creator_type": "author", "first_name": "Tetsuya J.", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Nobuko", "last_name": "Akiyama", "name": null }, { "creator_type": "author", "first_name": "Taishin", "last_name": "Akiyama", "name": null } ], "identifiers": { "doi": { "normalized": "10.3389/fimmu.2023.1186154" }, "pmcid": { "normalized": "PMC10652284" }, "pmid": { "normalized": "38022666" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Epithelial Cells", "descriptor_ui": "D004847", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Transcription Factors", "descriptor_ui": "D014157", "major_topic": true }, { "descriptor": "Transcriptome", "descriptor_ui": "D059467", "major_topic": true } ], "publication": { "conference_name": null, "date": "2023", "date_precision": "year", "issue": "", "normalized_date": "2023", "pages": "1186154", "proceedings_title": null, "publisher": "", "title": "Frontiers in immunology", "volume": "14", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Acute irradiation causes a long-term disturbance in the heterogeneity and gene expression profile of medullary thymic epithelial cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "A 61-year-old female was referred to our hospital because of pancytopenia and febrile neutropenia. On admission, computed tomography showed mild hepatosplenomegaly and intra-abdominal abscess formation in the right pelvic region; however, no lymphadenopathy was found. Bone marrow (BM) examination showed severe fibrosis by silver staining. Several small- to medium-sized lymphocytes with a constriction in the nuclei were observed, exhibiting CD3 (-), CD10 (-), CD20 (+), BCL-2 (+-), and CD138 (+-). Genetic testing revealed that BM cells were positive for MYD88 mutation and positive for IgH rearrangement, whereas neither JAK2 nor CALR mutation was positive. A diagnosis of BM infiltration of lymphoplasmacytic lymphoma (LPL) was made. Rituximab monotherapy was administered once a week for four times. BM examination 4 weeks after the end of treatment showed that lymphoma cells had disappeared and that myelofibrosis had been almost gone. The MYD88 mutation of BM turned out to be negative at that moment.", "classifications": [ { "id": "Nishikii", "label": "Group Nishikii", "parent": "Shintaku", "type": "group" }, { "id": "Shintaku", "label": "Team Shintaku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Ayako", "last_name": "Takarada", "name": null }, { "creator_type": "author", "first_name": "Haruka", "last_name": "Momose", "name": null }, { "creator_type": "author", "first_name": "Naoki", "last_name": "Kurita", "name": null }, { "creator_type": "author", "first_name": "Ryota", "last_name": "Matsuoka", "name": null }, { "creator_type": "author", "first_name": "Naoya", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Tasuhiro", "last_name": "Sakamoto", "name": null }, { "creator_type": "author", "first_name": "Takayasu", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Keiichiro", "last_name": "Hattori", "name": null }, { "creator_type": "author", "first_name": "Yasuhito", "last_name": "Suehara", "name": null }, { "creator_type": "author", "first_name": "Yasuhisa", "last_name": "Yokoyama", "name": null }, { "creator_type": "author", "first_name": "Hidekazu", "last_name": "Nishikii", "name": null }, { "creator_type": "author", "first_name": "Yumiko", "last_name": "Maruyama", "name": null }, { "creator_type": "author", "first_name": "Naoshi", "last_name": "Obara", "name": null }, { "creator_type": "author", "first_name": "Shigeru", "last_name": "Chiba", "name": null }, { "creator_type": "author", "first_name": "Mamiko", "last_name": "Sakata-Yanagimoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.11406/rinketsu.64.54" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "36775308" } }, "mesh": [ { "descriptor": "Bone Marrow", "descriptor_ui": "D001853", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Lymphoma, B-Cell", "descriptor_ui": "D016393", "major_topic": true }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Myeloid Differentiation Factor 88", "descriptor_ui": "D053594", "major_topic": false }, { "descriptor": "Primary Myelofibrosis", "descriptor_ui": "D055728", "major_topic": true }, { "descriptor": "Rituximab", "descriptor_ui": "D000069283", "major_topic": false }, { "descriptor": "Waldenstrom Macroglobulinemia", "descriptor_ui": "D008258", "major_topic": true } ], "publication": { "conference_name": null, "date": "2023", "date_precision": "year", "issue": "1", "normalized_date": "2023", "pages": "54-59", "proceedings_title": null, "publisher": "", "title": "[Rinsho ketsueki] The Japanese journal of clinical hematology", "volume": "64", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "[Lymphoplasmacytic lymphoma accompanied by severe myelofibrosis].", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Chronic manipulation in neonatal mice is a technical challenge, but it can achieve greater insights into how mice develop immediately after birth. However, these manipulations can often result in maternal rejection and consequently serious malnourishment and occasional death. Here, we describe a method to effectively hand rear mice to develop normally during the first post-natal week. In our experiments, we were able to negate the feeding deficiencies of anosmic mutant mice when compared to littermate controls. As a result, the delayed neuronal remodeling seen in maternally reared mutant mice was not seen in the hand-reared mutant mice. This methodology is user intensive but can be useful for a broad range of studies either requiring many interventions or one intervention that can result in maternal rejection or being outcompeted by healthy littermates.", "classifications": [ { "id": "Imai", "label": "Group Imai", "parent": "Enomoto", "type": "group" }, { "id": "Enomoto", "label": "Team Enomoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Leiwe", "last_name": "Marcus", "name": null }, { "creator_type": "author", "first_name": "Imai", "last_name": "Takeshi", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Imai", "name": null } ], "identifiers": { "doi": { "normalized": "10.21769/bioprotoc.4755" }, "pmcid": { "normalized": null }, "pmid": { "normalized": null } }, "mesh": [], "publication": { "conference_name": null, "date": "2023", "date_precision": "year", "issue": "11", "normalized_date": "2023", "pages": "", "proceedings_title": null, "publisher": "", "title": "BIO-PROTOCOL", "volume": "13", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Effective Hand Rearing of Neonatal Mice for Developmental Studies", "url": "https://bio-protocol.org/e4755", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Parental care plays a crucial role in the physical and mental well-being of mammalian offspring. Although sexually naive male mice, as well as certain strains of female mice, display aggression toward pups, they exhibit heightened parental caregiving behaviors as they approach the time of anticipating their offspring. In this Mini Review, I provide a concise overview of the current understanding of distinct limbic neural types and their circuits governing both aggressive and caregiving behaviors toward infant mice. Subsequently, I delve into recent advancements in the understanding of the molecular, cellular, and neural circuit mechanisms that regulate behavioral plasticity during the transition to parenthood, with a specific focus on the sex steroid hormone estrogen and neural hormone oxytocin. Additionally, I explore potential sex-related differences and highlight some critical unanswered questions that warrant further investigation.", "classifications": [ { "id": "Miyamichi", "label": "Group Miyamichi", "parent": "Enomoto", "type": "group" }, { "id": "Enomoto", "label": "Team Enomoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Kazunari", "last_name": "Miyamichi", "name": null } ], "identifiers": { "doi": { "normalized": "10.3389/fncir.2023.1340497" }, "pmcid": { "normalized": "PMC10829089" }, "pmid": { "normalized": "38298741" } }, "mesh": [ { "descriptor": "Aggression", "descriptor_ui": "D000374", "major_topic": true }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mammals", "descriptor_ui": "D008322", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Oxytocin", "descriptor_ui": "D010121", "major_topic": false }, { "descriptor": "Paternal Behavior", "descriptor_ui": "D010332", "major_topic": true } ], "publication": { "conference_name": null, "date": "2023", "date_precision": "year", "issue": "", "normalized_date": "2023", "pages": "1340497", "proceedings_title": null, "publisher": "", "title": "Frontiers in neural circuits", "volume": "17", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Neural basis for behavioral plasticity during the parental life-stage transition in mice.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND AND AIMS: To examine the roles of microRNAs in the development of colitis, we conducted the RNA-sequencing studies using RNA derived from normal and colitogenic CD4+ T cells. Colitogenic CD4(+) T cells demonstrated the increased expression of miR-150. We focused on the involvement of miR-150 in the colitis. METHODS: We crossed miR-150 knockout mice and T-cell-specific Rap1KO mice, which is colitis model mice and spontaneously develop the colitis with tubular adenomas in microbiota-dependent manner. RESULTS: MiR-150 silencing completely inhibited the expansion of pathogenic Th17 cells and the development of colitis. CONCLUSION: MiR-150 is a potential therapeutic target of inflammatory bowel diseases.", "classifications": [ { "id": "Sawai", "label": "Group Sawai", "parent": "Sawai", "type": "group" }, { "id": "Sawai", "label": "Team Sawai", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Sayaka", "last_name": "Ishihara", "name": null }, { "creator_type": "author", "first_name": "Masashi", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Haruka", "last_name": "Miyazaki", "name": null }, { "creator_type": "author", "first_name": "Haruka", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Tsuyoshi", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Noriyuki", "last_name": "Fujikado", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Sawai", "name": null }, { "creator_type": "author", "first_name": "Ai", "last_name": "Kotani", "name": null }, { "creator_type": "author", "first_name": "Koko", "last_name": "Katagiri", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.gastha.2023.01.021" }, "pmcid": { "normalized": "PMC11308117" }, "pmid": { "normalized": "39132043" } }, "mesh": [], "publication": { "conference_name": null, "date": "2023", "date_precision": "year", "issue": "4", "normalized_date": "2023", "pages": "487-496", "proceedings_title": null, "publisher": "", "title": "Gastro hep advances", "volume": "2", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Deletion of miR-150 Prevents Spontaneous T Cell Proliferation and the Development of Colitis.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Introduction: Periodic organ arrangements occur during growth and development and are widespread in animals and plants. In bilaterian animals, repetitive organs can be interpreted as being periodically arranged along the two-dimensional space and defined by two body axes; on the other hand, in radially symmetrical animals and plants, organs are arranged in the three-dimensional space around the body axis and around plant stems, respectively. The principles of periodic organ arrangement have primarily been investigated in bilaterians; however, studies on this phenomenon in radially symmetrical animals are scarce. Methods: In the present study, we combined live imaging, quantitative analysis, and mathematical modeling to elucidate periodic organ arrangement in a radially symmetrical animal, Coryne uchidai (Cnidaria, Hydrozoa). Results: The polyps of C. uchidai simultaneously formed multiple tentacles to establish a regularly angled, ring-like arrangement with radial symmetry. Multiple rings periodically appeared throughout the body and mostly maintained symmetry. Furthermore, we observed polymorphisms in symmetry type, including tri-, tetra-, and pentaradial symmetries, as individual variations. Notably, the types of radial symmetry were positively correlated with polyp diameter, with a larger diameter in pentaradial polyps than in tetra- and triradial ones. Our mathematical model suggested the selection of size-correlated radial symmetry based on the activation-inhibition and positional information from the mouth of tentacle initiation. Discussion: Our established quantification methods and mathematical model for tentacle arrangements are applicable to other radially symmetrical animals, and will reveal the widespread association between size-correlated symmetry and periodic arrangement principles.", "classifications": [ { "id": "Fujimoto", "label": "Group Fujimoto", "parent": "Ueda", "type": "group" }, { "id": "Ueda", "label": "Team Ueda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Safiye E.", "last_name": "Sarper", "name": null }, { "creator_type": "author", "first_name": "Miho S.", "last_name": "Kitazawa", "name": null }, { "creator_type": "author", "first_name": "Tamami", "last_name": "Nakanishi", "name": null }, { "creator_type": "author", "first_name": "Koichi", "last_name": "Fujimoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.3389/fcell.2023.1284904" }, "pmcid": { "normalized": "PMC10703359" }, "pmid": { "normalized": "38078002" } }, "mesh": [], "publication": { "conference_name": null, "date": "2023", "date_precision": "year", "issue": "", "normalized_date": "2023", "pages": "1284904", "proceedings_title": null, "publisher": "", "title": "Frontiers in cell and developmental biology", "volume": "11", "year": 2023 }, "ssbd": { "database": [ "ssbd-database-000408" ], "repository": [ "ssbd-repos-000408" ] }, "title": "Size-correlated polymorphisms in phyllotaxis-like periodic and symmetric tentacle arrangements in hydrozoan Coryne uchidai.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND AND AIMS: Corticotropin-releasing hormone (CRH) is a major regulator of the stress response to internal and external factors. CRH and its receptors (CRHR1 and CRHR2) are expressed in the central nervous system and some cancer cells, suggesting the importance of CRH signaling in pancreatic cancers. However, the clinicopathological significance of CRH remains unknown because the immunolocalization of CRH, CRHR1, and CRHR2 has not been examined in pancreatic carcinoma tissues. We clarified the correlation of the expression of CRH and its receptors with overall survival in pancreatic cancer. METHODS: This study evaluated 96 patients with pancreatic cancer who underwent microscopic complete resection (R0) but not neoadjuvant chemotherapy from 1988 to 2007 at Tohoku University Hospital, Japan. CRH, CRHR1, and CRHR2 immunoreactivity were detected in the pancreatic carcinoma cells. Overall survival curves were generated according to the Kaplan-Meier method. RESULTS: CRHR1 immunoreactivity was significantly associated with an increased risk of poorer prognosis in all patients (P = .038) and the adjuvant therapy group (P = .022). Overall survival was worse in the CRHR1-positive group than in the CRHR1-negative group among the 62 patients treated with gemcitabine hydrochloride (P = .046) and the 22 patients treated with other drugs (P = .047). CRHR1 expression was correlated with survival in univariate analysis but not in multivariate analysis. CONCLUSION: This study is the first to immunolocalize CRH, CRHR1, and CRHR2 in pancreatic carcinoma tissues and to examine the biological prognosis. This study revealed that survival in patients with pancreatic cancer was significantly associated with expression of CRHR1 by assessing biological progression according to CRH and the expression of its receptors. However, CRHR1 expression was correlated with survival in univariate analysis but not in multivariate analysis.", "classifications": [ { "id": "Suzuki", "label": "Group Suzuki", "parent": "Takekawa", "type": "group" }, { "id": "Takekawa", "label": "Team Takekawa", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Naoko", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Fuyuhiko", "last_name": "Motoi", "name": null }, { "creator_type": "author", "first_name": "Hana", "last_name": "Tajiki", "name": null }, { "creator_type": "author", "first_name": "Kei", "last_name": "Kawaguchi", "name": null }, { "creator_type": "author", "first_name": "Hideo", "last_name": "Ohtsuka", "name": null }, { "creator_type": "author", "first_name": "Tatuyuki", "last_name": "Takadate", "name": null }, { "creator_type": "author", "first_name": "Kei", "last_name": "Nakagawa", "name": null }, { "creator_type": "author", "first_name": "Kiyoshi", "last_name": "Takagi", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Yu", "last_name": "Katayose", "name": null }, { "creator_type": "author", "first_name": "Shin", "last_name": "Fukudo", "name": null }, { "creator_type": "author", "first_name": "Michiaki", "last_name": "Unno", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.gastha.2022.09.003" }, "pmcid": { "normalized": "PMC11308248" }, "pmid": { "normalized": "39130148" } }, "mesh": [], "publication": { "conference_name": null, "date": "2023", "date_precision": "year", "issue": "1", "normalized_date": "2023", "pages": "147-155", "proceedings_title": null, "publisher": "", "title": "Gastro hep advances", "volume": "2", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Expression of Corticotropin-Releasing Hormone and Its Receptors May Be Associated With Survival Rate in Pancreatic Cancer.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "A 51-year-old man with the chief complaint of glove- and stocking-type dysesthesia for >3 years was diagnosed with Waldenstrom's macroglobulinemia (WM) based on IgM-type M-proteinemia, bone marrow infiltration of plasmacytoid B cells, multiple lymphadenopathies, and splenomegaly. A nerve conduction examination suggested demyelinating neuropathy. Serum anti-myelin-associated glycoprotein antibody was negative. Sural nerve biopsy showed myelin thinning, suggesting demyelination. Axonal damage and tumor cell infiltration in the intrafascicular epineurium were also observed. After chemotherapies with rituximab and bendamustine, M-proteinemia and lymphadenopathies disappeared. However, abnormalities in the nerve conduction examination and dysesthesia were only slightly alleviated. As articles describing patients with WM with peripheral nerve infiltration are limited, we report this case with a literature review.", "classifications": [ { "id": "Nishikii", "label": "Group Nishikii", "parent": "Shintaku", "type": "group" }, { "id": "Shintaku", "label": "Team Shintaku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Natsuki", "last_name": "Norioka", "name": null }, { "creator_type": "author", "first_name": "Naoki", "last_name": "Kurita", "name": null }, { "creator_type": "author", "first_name": "Yuya", "last_name": "Kamura", "name": null }, { "creator_type": "author", "first_name": "Tatsuhiro", "last_name": "Sakamoto", "name": null }, { "creator_type": "author", "first_name": "Takayasu", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Yasuhisa", "last_name": "Yokoyama", "name": null }, { "creator_type": "author", "first_name": "Hidekazu", "last_name": "Nishikii", "name": null }, { "creator_type": "author", "first_name": "Naoshi", "last_name": "Obara", "name": null }, { "creator_type": "author", "first_name": "Mamiko", "last_name": "Sakata-Yanagimoto", "name": null }, { "creator_type": "author", "first_name": "Hana", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Kiyotaka", "last_name": "Nakamagoe", "name": null }, { "creator_type": "author", "first_name": "Akiko", "last_name": "Ishii", "name": null }, { "creator_type": "author", "first_name": "Ryota", "last_name": "Matsuoka", "name": null }, { "creator_type": "author", "first_name": "Toru", "last_name": "Nanmoku", "name": null }, { "creator_type": "author", "first_name": "Akira", "last_name": "Tamaoka", "name": null }, { "creator_type": "author", "first_name": "Shigeru", "last_name": "Chiba", "name": null } ], "identifiers": { "doi": { "normalized": "10.11406/rinketsu.64.18" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "36775301" } }, "mesh": [ { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Immunoglobulin M", "descriptor_ui": "D007075", "major_topic": false }, { "descriptor": "Lymphadenopathy", "descriptor_ui": "D000072281", "major_topic": true }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Paresthesia", "descriptor_ui": "D010292", "major_topic": false }, { "descriptor": "Peripheral Nervous System Diseases", "descriptor_ui": "D010523", "major_topic": true }, { "descriptor": "Rituximab", "descriptor_ui": "D000069283", "major_topic": false }, { "descriptor": "Waldenstrom Macroglobulinemia", "descriptor_ui": "D008258", "major_topic": true } ], "publication": { "conference_name": null, "date": "2023", "date_precision": "year", "issue": "1", "normalized_date": "2023", "pages": "18-22", "proceedings_title": null, "publisher": "", "title": "[Rinsho ketsueki] The Japanese journal of clinical hematology", "volume": "64", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "[Waldenstrom macroglobulinemia complicated by peripheral neuropathy due to neural infiltration].", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The hormone oxytocin, secreted from oxytocin neurons in the paraventricular (PVH) and supraoptic (SO) hypothalamic nuclei, promotes parturition, milk ejection, and maternal caregiving behaviors. Previous experiments with whole-body oxytocin knockout mice showed that milk ejection was the unequivocal function of oxytocin, whereas parturition and maternal behaviors were less dependent on oxytocin. Whole-body knockout, however, could induce the enhancement of expression of related gene(s), a phenomenon called genetic compensation, which may hide the actual functions of oxytocin. In addition, the relative contributions of oxytocin neurons in the PVH and SO have not been well documented. Here, we show that females with conditional knockout of oxytocin gene in both the PVH and SO undergo grossly normal parturition and maternal caregiving behaviors, while dams with a smaller number of remaining oxytocin-expressing neurons exhibit severe impairments in breastfeeding, leading to the death of their pups within 24 hours after birth. We also found that the growth of pups is normal even under oxytocin conditional knockout in PVH and SO as long as pups survive the next day of delivery, suggesting that the reduced oxytocin release affects the onset of lactation most severely. These phenotypes are largely recapitulated by SO-specific oxytocin conditional knockout, indicating the unequivocal role of oxytocin neurons in the SO in successful breastfeeding. Given that oxytocin neurons not only secrete oxytocin but also non-oxytocin neurotransmitters or neuropeptides, we further performed cell ablation of oxytocin neurons in the PVH and SO. We found that cell ablation of oxytocin neurons leads to no additional abnormalities over the oxytocin conditional knockout, suggesting that non-oxytocin ligands expressed by oxytocin neurons have negligible functions on the responses measured in this study. Collectively, our findings confirm the dispensability of oxytocin for parturition or maternal behaviors, as well as the importance of SO-derived oxytocin for breastfeeding.", "classifications": [ { "id": "Miyamichi", "label": "Group Miyamichi", "parent": "Enomoto", "type": "group" }, { "id": "Enomoto", "label": "Team Enomoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Mitsue", "last_name": "Hagihara", "name": null }, { "creator_type": "author", "first_name": "Kazunari", "last_name": "Miyamichi", "name": null }, { "creator_type": "author", "first_name": "Kengo", "last_name": "Inada", "name": null } ], "identifiers": { "doi": { "normalized": "10.1371/journal.pone.0283152" }, "pmcid": { "normalized": "PMC10022762" }, "pmid": { "normalized": "36930664" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Hypothalamus", "descriptor_ui": "D007031", "major_topic": false }, { "descriptor": "Lactation", "descriptor_ui": "D007774", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Oxytocin", "descriptor_ui": "D010121", "major_topic": true }, { "descriptor": "Paraventricular Hypothalamic Nucleus", "descriptor_ui": "D010286", "major_topic": false }, { "descriptor": "Supraoptic Nucleus", "descriptor_ui": "D013495", "major_topic": true } ], "publication": { "conference_name": null, "date": "2023", "date_precision": "year", "issue": "3", "normalized_date": "2023", "pages": "e0283152", "proceedings_title": null, "publisher": "", "title": "PloS one", "volume": "18", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "The importance of oxytocin neurons in the supraoptic nucleus for breastfeeding in mice.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Large vacuoles are a predominant cell organelle throughout the plant body. They maximally account for over 90% of cell volume and generate turgor pressure that acts as a driving force of cell growth, which is essential for plant development. The plant vacuole also acts as a reservoir for sequestering waste products and apoptotic enzymes, thereby enabling plants to rapidly respond to fluctuating environments. Vacuoles undergo dynamic transformation through repeated enlargement, fusion, fragmentation, invagination, and constriction, eventually resulting in the typical 3-dimensional complex structure in each cell type. Previous studies have indicated that such dynamic transformations of plant vacuoles are governed by the plant cytoskeletons, which consist of F-actin and microtubules. However, the molecular mechanism of cytoskeleton-mediated vacuolar modifications remains largely unclear. Here we first review the behavior of cytoskeletons and vacuoles during plant development and in response to environmental stresses, and then introduce candidates that potentially play pivotal roles in the vacuole–cytoskeleton nexus. Finally, we discuss factors hampering the advances in this research field and their possible solutions using the currently available cutting-edge technologies.", "classifications": [ { "id": "JPMJCR2121", "label": "JPMJCR2121", "researcher": "Minako Ueda", "type": "grant" }, { "id": "Higaki", "label": "Group Higaki", "parent": "Ueda", "type": "group" }, { "id": "Ueda", "label": "Group Ueda", "parent": "Ueda", "type": "group" }, { "id": "Ueda", "label": "Team Ueda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Hirotomo", "last_name": "Takatsuka", "name": null }, { "creator_type": "author", "first_name": "Takumi", "last_name": "Higaki", "name": null }, { "creator_type": "author", "first_name": "Masaki", "last_name": "Ito", "name": null } ], "identifiers": { "doi": { "normalized": "10.3390/ijms24044143" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "36835552" } }, "mesh": [ { "descriptor": "Actin Cytoskeleton", "descriptor_ui": "D008841", "major_topic": false }, { "descriptor": "Cytoskeleton", "descriptor_ui": "D003599", "major_topic": true }, { "descriptor": "Microtubules", "descriptor_ui": "D008870", "major_topic": false }, { "descriptor": "Plants", "descriptor_ui": "D010944", "major_topic": false }, { "descriptor": "Vacuoles", "descriptor_ui": "D014617", "major_topic": true } ], "publication": { "conference_name": null, "date": "2023 Feb", "date_precision": "unknown", "issue": "4", "normalized_date": null, "pages": "", "proceedings_title": null, "publisher": "", "title": "International Journal of Molecular Sciences", "volume": "24", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "At the Nexus between Cytoskeleton and Vacuole: How Plant Cytoskeletons Govern the Dynamics of Large Vacuoles.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The endoplasmic reticulum (ER)-embedded transcription factors, sterol regulatory element-binding proteins (SREBPs), master regulators of lipid biosynthesis, are transported to the Golgi for proteolytic activation to tune cellular cholesterol levels and regulate lipogenesis. However, mechanisms by which the cell responds to the levels of saturated or unsaturated fatty acids remain underexplored. Here, we show that RHBDL4/RHBDD1, a rhomboid family protease, directly cleaves SREBP-1c at the ER. The p97/VCP, AAA-ATPase complex then acts as an auxiliary segregase to extract the remaining ER-embedded fragment of SREBP-1c. Importantly, the enzymatic activity of RHBDL4 is enhanced by saturated fatty acids (SFAs) but inhibited by polyunsaturated fatty acids (PUFAs). Genetic deletion of RHBDL4 in mice fed on a Western diet enriched in SFAs and cholesterol prevented SREBP-1c from inducing genes for lipogenesis, particularly for synthesis and incorporation of PUFAs, and secretion of lipoproteins. The RHBDL4-SREBP-1c pathway reveals a regulatory system for monitoring fatty acid composition and maintaining cellular lipid homeostasis.", "classifications": [ { "id": "Miyamoto", "label": "Group Miyamoto", "parent": "Wakamoto", "type": "group" }, { "id": "Wakamoto", "label": "Team Wakamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Song-Iee", "last_name": "Han", "name": null }, { "creator_type": "author", "first_name": "Masanori", "last_name": "Nakakuki", "name": null }, { "creator_type": "author", "first_name": "Yoshimi", "last_name": "Nakagawa", "name": null }, { "creator_type": "author", "first_name": "Yunong", "last_name": "Wang", "name": null }, { "creator_type": "author", "first_name": "Masaya", "last_name": "Araki", "name": null }, { "creator_type": "author", "first_name": "Yuta", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Hiroaki", "last_name": "Tokiwa", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Takeda", "name": null }, { "creator_type": "author", "first_name": "Yuhei", "last_name": "Mizunoe", "name": null }, { "creator_type": "author", "first_name": "Kaori", "last_name": "Motomura", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Ohno", "name": null }, { "creator_type": "author", "first_name": "Kenta", "last_name": "Kainoh", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Murayama", "name": null }, { "creator_type": "author", "first_name": "Yuichi", "last_name": "Aita", "name": null }, { "creator_type": "author", "first_name": "Yoshinori", "last_name": "Takeuchi", "name": null }, { "creator_type": "author", "first_name": "Yoshinori", "last_name": "Osaki", "name": null }, { "creator_type": "author", "first_name": "Takafumi", "last_name": "Miyamoto", "name": null }, { "creator_type": "author", "first_name": "Motohiro", "last_name": "Sekiya", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Matsuzaka", "name": null }, { "creator_type": "author", "first_name": "Naoya", "last_name": "Yahagi", "name": null }, { "creator_type": "author", "first_name": "Hirohito", "last_name": "Sone", "name": null }, { "creator_type": "author", "first_name": "Hiroaki", "last_name": "Daitoku", "name": null }, { "creator_type": "author", "first_name": "Ryuichiro", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Kawano", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Shimano", "name": null } ], "identifiers": { "doi": { "normalized": "10.1093/pnasnexus/pgad351" }, "pmcid": { "normalized": "PMC10637267" }, "pmid": { "normalized": "37954160" } }, "mesh": [], "publication": { "conference_name": null, "date": "2023 Nov", "date_precision": "unknown", "issue": "11", "normalized_date": null, "pages": "pgad351", "proceedings_title": null, "publisher": "", "title": "PNAS nexus", "volume": "2", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Rhomboid protease RHBDL4/RHBDD1 cleaves SREBP-1c at endoplasmic reticulum monitoring and regulating fatty acids.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.jtocrr.2023.100492" }, "pmcid": { "normalized": "PMC10023938" }, "pmid": { "normalized": "36942129" } }, "mesh": [], "publication": { "conference_name": null, "date": "2023 Mar", "date_precision": "unknown", "issue": "3", "normalized_date": null, "pages": "100492", "proceedings_title": null, "publisher": "", "title": "JTO clinical and research reports", "volume": "4", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Comments on the Article by Miura et al.: \"Comparable Clinical Benefit Between Different Subsets Selected by PD-L1 22C3 and SP142 Tests\".", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Reactive sulfur species, or persulfides and polysulfides, such as cysteine hydropersulfide and glutathione persulfide, are endogenously produced in abundance in both prokaryotes and eukaryotes, including mammals. Various forms of reactive persulfides occur in both low-molecular-weight and protein-bound thiols. The chemical properties and great supply of these molecular species suggest a pivotal role for reactive persulfides/polysulfides in different cellular regulatory processes (e.g., energy metabolism and redox signaling). We demonstrated earlier that cysteinyl-tRNA synthetase (CARS) is a new cysteine persulfide synthase (CPERS) and is responsible for the in vivo production of most reactive persulfides (polysulfides). Some researchers continue to suggest that 3-mercaptopyruvate sulfurtransferase (3-MST), cystathionine β-synthase (CBS), and cystathionine γ-lyase (CSE) may also produce hydrogen sulfide and persulfides that may be generated during the transfer of sulfur from 3-mercaptopyruvate to the cysteine residues of 3-MST or direct synthesis from cysteine by CBS/CSE, respectively. We thus used integrated sulfur metabolome analysis, which we recently developed, with 3-MST knockout (KO) mice and CBS/CSE/3-MST triple-KO mice, to elucidate the possible contribution of 3-MST, CBS, and CSE to the production of reactive persulfides in vivo. We therefore quantified various sulfide metabolites in organs derived from these mutant mice and their wild-type littermates via this sulfur metabolome, which clearly revealed no significant difference between mutant mice and wild-type mice in terms of reactive persulfide production. This result indicates that 3-MST, CBS, and CSE are not major sources of endogenous reactive persulfide production; rather, CARS/CPERS is the principal enzyme that is actually involved in and even primarily responsible for the biosynthesis of reactive persulfides and polysulfides in vivo in mammals.", "classifications": [ { "id": "JPMJCR2024", "label": "JPMJCR2024", "researcher": "Motohiro Nishida", "type": "grant" }, { "id": "Akaike", "label": "Group Akaike", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Group Nishida", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Qamarul Hafiz", "last_name": "Zainol Abidin", "name": null }, { "creator_type": "author", "first_name": "Tomoaki", "last_name": "Ida", "name": null }, { "creator_type": "author", "first_name": "Masanobu", "last_name": "Morita", "name": null }, { "creator_type": "author", "first_name": "Tetsuro", "last_name": "Matsunaga", "name": null }, { "creator_type": "author", "first_name": "Akira", "last_name": "Nishimura", "name": null }, { "creator_type": "author", "first_name": "Minkyung", "last_name": "Jung", "name": null }, { "creator_type": "author", "first_name": "Naim", "last_name": "Hassan", "name": null }, { "creator_type": "author", "first_name": "Tsuyoshi", "last_name": "Takata", "name": null }, { "creator_type": "author", "first_name": "Isao", "last_name": "Ishii", "name": null }, { "creator_type": "author", "first_name": "Warren", "last_name": "Kruger", "name": null }, { "creator_type": "author", "first_name": "Rui", "last_name": "Wang", "name": null }, { "creator_type": "author", "first_name": "Hozumi", "last_name": "Motohashi", "name": null }, { "creator_type": "author", "first_name": "Masato", "last_name": "Tsutsui", "name": null }, { "creator_type": "author", "first_name": "Takaaki", "last_name": "Akaike", "name": null } ], "identifiers": { "doi": { "normalized": "10.3390/antiox12040868" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "37107243" } }, "mesh": [], "publication": { "conference_name": null, "date": "2023 Apr", "date_precision": "unknown", "issue": "4", "normalized_date": null, "pages": "", "proceedings_title": null, "publisher": "", "title": "Antioxidants", "volume": "12", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Synthesis of Sulfides and Persulfides Is Not Impeded by Disruption of Three Canonical Enzymes in Sulfur Metabolism.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Flow cytometry is an indispensable tool in biology and medicine for counting and analyzing cells in large heterogeneous populations. It identifies multiple characteristics of every single cell, typically via fluorescent probes that specifically bind to target molecules on the cell surface or within the cell. However, flow cytometry has a critical limitation: the color barrier. The number of chemical traits that can be simultaneously resolved is typically limited to several due to the spectral overlap between fluorescence signals from different fluorescent probes. Here, we present color-scalable flow cytometry based on coherent Raman flow cytometry with Raman tags to break the color barrier. This is made possible by combining a broadband Fourier-transform coherent anti-Stokes Raman scattering (FT-CARS) flow cytometer, resonance-enhanced cyanine-based Raman tags, and Raman-active dots (Rdots). Specifically, we synthesized 20 cyanine-based Raman tags whose Raman spectra are linearly independent in the fingerprint region (400 to 1,600 cm−1). For highly sensitive detection, we produced Rdots composed of 12 different Raman tags in polymer nanoparticles whose detection limit was as low as 12 nM for a short FT-CARS signal integration time of 420 µs. We performed multiplex flow cytometry of MCF-7 breast cancer cells stained by 12 different Rdots with a high classification accuracy of 98%. Moreover, we demonstrated a large-scale time-course analysis of endocytosis via the multiplex Raman flow cytometer. Our method can theoretically achieve flow cytometry of live cells with >140 colors based on a single excitation laser and a single detector without increasing instrument size, cost, or complexity.", "classifications": [ { "id": "JPMJCR1925", "label": "JPMJCR1925", "researcher": "Katsumasa Fujita", "type": "grant" }, { "id": "Fujita", "label": "Group Fujita", "parent": "Fujita", "type": "group" }, { "id": "Sodeoka", "label": "Group Sodeoka", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Ryo", "last_name": "Nishiyama", "name": null }, { "creator_type": "author", "first_name": "Kotaro", "last_name": "Hiramatsu", "name": null }, { "creator_type": "author", "first_name": "Shintaro", "last_name": "Kawamura", "name": null }, { "creator_type": "author", "first_name": "Kosuke", "last_name": "Dodo", "name": null }, { "creator_type": "author", "first_name": "Kei", "last_name": "Furuya", "name": null }, { "creator_type": "author", "first_name": "Julia Gala", "last_name": "de Pablo", "name": null }, { "creator_type": "author", "first_name": "Shigekazu", "last_name": "Takizawa", "name": null }, { "creator_type": "author", "first_name": "Wei", "last_name": "Min", "name": null }, { "creator_type": "author", "first_name": "Mikiko", "last_name": "Sodeoka", "name": null }, { "creator_type": "author", "first_name": "Keisuke", "last_name": "Goda", "name": null } ], "identifiers": { "doi": { "normalized": "10.1093/pnasnexus/pgad001" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "36845353" } }, "mesh": [], "publication": { "conference_name": null, "date": "2023 Feb", "date_precision": "unknown", "issue": "2", "normalized_date": null, "pages": "", "proceedings_title": null, "publisher": "", "title": "PNAS Nexus", "volume": "2", "year": 2023 }, "ssbd": { "database": [ "ssbd-database-000300" ], "repository": [ "ssbd-repos-000300" ] }, "title": "Color-scalable flow cytometry with Raman tags.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "AIM: Gastrectomy is recommended for patients with early gastric cancer (EGC) because the possibility of lymph node metastasis (LNM) cannot be completely denied. The aim of this study was to develop a discrimination model to select patients who do not require surgery using machine learning. METHODS: Data from 382 patients who received gastrectomy for gastric cancer and who were diagnosed with pT1b were extracted for developing a discrimination model. For the validation of this discrimination model, data from 140 consecutive patients who underwent endoscopic resection followed by gastrectomy, with a diagnosis of pT1b EGC, were extracted. We applied XGBoost to develop a discrimination model for clinical and pathological variables. The performance of the discrimination model was evaluated based on the number of cases classified as true negatives for LNM, with no false negatives for LNM allowed. RESULTS: Lymph node metastasis was observed in 95 patients (25%) in the development cohort and 11 patients (8%) in the validation cohort. The discrimination model was developed to identify 27 (7%) patients with no indications for additional surgery due to the prediction of an LNM-negative status with no false negatives. In the validation cohort, 13 (9%) patients were identified as having no indications for additional surgery and no patients with LNM were classified into this group. CONCLUSION: The discrimination model using XGBoost algorithms could select patients with no risk of LNM from patients with pT1b EGC. This discrimination model was considered promising for clinical decision-making in relation to patients with EGC.", "classifications": [ { "id": "Hamamoto", "label": "Group Hamamoto", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Tsutomu", "last_name": "Hayashi", "name": null }, { "creator_type": "author", "first_name": "Ken", "last_name": "Takasawa", "name": null }, { "creator_type": "author", "first_name": "Takaki", "last_name": "Yoshikawa", "name": null }, { "creator_type": "author", "first_name": "Taiki", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Shigeki", "last_name": "Sekine", "name": null }, { "creator_type": "author", "first_name": "Takeyuki", "last_name": "Wada", "name": null }, { "creator_type": "author", "first_name": "Yukinori", "last_name": "Yamagata", "name": null }, { "creator_type": "author", "first_name": "Haruhisa", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Seiichirou", "last_name": "Abe", "name": null }, { "creator_type": "author", "first_name": "Shigetaka", "last_name": "Yoshinaga", "name": null }, { "creator_type": "author", "first_name": "Yutaka", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Nobuji", "last_name": "Kouno", "name": null }, { "creator_type": "author", "first_name": "Ryuji", "last_name": "Hamamoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/ags3.12714" }, "pmcid": { "normalized": "PMC10623978" }, "pmid": { "normalized": "37927931" } }, "mesh": [], "publication": { "conference_name": null, "date": "2023 Nov", "date_precision": "unknown", "issue": "6", "normalized_date": null, "pages": "913-921", "proceedings_title": null, "publisher": "", "title": "Annals of gastroenterological surgery", "volume": "7", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "A discrimination model by machine learning to avoid gastrectomy for early gastric cancer.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yu", "last_name": "Okubo", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.jtho.2023.02.006" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "37087120" } }, "mesh": [ { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Lung Neoplasms", "descriptor_ui": "D008175", "major_topic": true }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false } ], "publication": { "conference_name": null, "date": "2023 May", "date_precision": "unknown", "issue": "5", "normalized_date": null, "pages": "e46-e48", "proceedings_title": null, "publisher": "", "title": "Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer", "volume": "18", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Reply to the Letter to the Editor From He Y et al.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Cutaneous adnexal tumors are neoplasms that arise from skin appendages. Their morphologic diversity and phenotypic variability with rare progression to malignancy make them difficult to diagnose and classify, and there is currently no established treatment strategy. To overcome these difficulties, this study investigated the transcription factor SOX9 expression, morphology, and genetics of skin adnexal tumors for understanding their biology, especially their histogenesis. We showed that cutaneous adnexal tumors and their nontumor counterparts of skin and appendages exhibit expression patterns similar to that of SOX9. Its expression intensity and pattern, as well as histopathologic evaluation of tumors, were analyzed using digital images of 69 normal skin adnexal 9-type organs and 185 skin adnexal 29-type tumors as references. It was possible to distinguish basal cell carcinoma from squamous cell carcinoma, sebaceous carcinoma, and pilomatrixoma with significant differences, along with porocarcinoma from squamous cell carcinoma. Furthermore, unsupervised machine learning \"computational pathology\" was used to derive a multiregion whole-exome sequencing fusion method termed \"genocomputed pathology.\" The genocomputed pathology of three representable adnexal carcinomas (porocarcinoma, hidradenocarcinoma, and spiradenocarcinoma) was evaluated for total nine cases. We showed that there was more heterogeneity than expected within the tumors as well as the coexistence of components lacking driver fusion genes. The presence or absence of potential driver genes, such as PIK3CA, YAP1, and PTEN, in each region was identified, highlighting a therapeutic strategy for cutaneous adnexal carcinoma encompassing heterogeneous tumors.", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yuuki", "last_name": "Nishimura", "name": null }, { "creator_type": "author", "first_name": "Eijitsu", "last_name": "Ryo", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Inoue", "name": null }, { "creator_type": "author", "first_name": "Masahito", "last_name": "Kawazu", "name": null }, { "creator_type": "author", "first_name": "Toshihide", "last_name": "Ueno", "name": null }, { "creator_type": "author", "first_name": "Kenjiro", "last_name": "Namikawa", "name": null }, { "creator_type": "author", "first_name": "Akira", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Dai", "last_name": "Ogata", "name": null }, { "creator_type": "author", "first_name": "Akihiko", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Naoya", "last_name": "Yamazaki", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Mano", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null }, { "creator_type": "author", "first_name": "Taisuke", "last_name": "Mori", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.xjidi.2023.100229" }, "pmcid": { "normalized": "PMC10641284" }, "pmid": { "normalized": "37965425" } }, "mesh": [], "publication": { "conference_name": null, "date": "2023 Nov", "date_precision": "unknown", "issue": "6", "normalized_date": null, "pages": "100229", "proceedings_title": null, "publisher": "", "title": "JID innovations : skin science from molecules to population health", "volume": "3", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Strategic Approach to Heterogeneity Analysis of Cutaneous Adnexal Carcinomas Using Computational Pathology and Genomics.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Label-free super-resolution (LFSR) imaging relies on light-scattering processes in nanoscale objects without a need for fluorescent (FL) staining required in super-resolved FL microscopy. The objectives of this Roadmap are to present a comprehensive vision of the developments, the state-of-the-art in this field, and to discuss the resolution boundaries and hurdles which need to be overcome to break the classical diffraction limit of the LFSR imaging. The scope of this Roadmap spans from the advanced interference detection techniques, where the diffraction-limited lateral resolution is combined with unsurpassed axial and temporal resolution, to techniques with true lateral super-resolution capability which are based on understanding resolution as an information science problem, on using novel structured illumination, near-field scanning, and nonlinear optics approaches, and on designing superlenses based on nanoplasmonics, metamaterials, transformation optics, and microsphere-assisted approaches. To this end, this Roadmap brings under the same umbrella researchers from the physics and biomedical optics communities in which such studies have often been developing separately. The ultimate intent of this paper is to create a vision for the current and future developments of LFSR imaging based on its physical mechanisms and to create a great opening for the series of articles in this field.", "classifications": [ { "id": "Fujita", "label": "Group Fujita", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Vasily N.", "last_name": "Astratov", "name": null }, { "creator_type": "author", "first_name": "Yair Ben", "last_name": "Sahel", "name": null }, { "creator_type": "author", "first_name": "Yonina C.", "last_name": "Eldar", "name": null }, { "creator_type": "author", "first_name": "Luzhe", "last_name": "Huang", "name": null }, { "creator_type": "author", "first_name": "Aydogan", "last_name": "Ozcan", "name": null }, { "creator_type": "author", "first_name": "Nikolay", "last_name": "Zheludev", "name": null }, { "creator_type": "author", "first_name": "Junxiang", "last_name": "Zhao", "name": null }, { "creator_type": "author", "first_name": "Zachary", "last_name": "Burns", "name": null }, { "creator_type": "author", "first_name": "Zhaowei", "last_name": "Liu", "name": null }, { "creator_type": "author", "first_name": "Evgenii", "last_name": "Narimanov", "name": null }, { "creator_type": "author", "first_name": "Neha", "last_name": "Goswami", "name": null }, { "creator_type": "author", "first_name": "Gabriel", "last_name": "Popescu", "name": null }, { "creator_type": "author", "first_name": "Emanuel", "last_name": "Pfitzner", "name": null }, { "creator_type": "author", "first_name": "Philipp", "last_name": "Kukura", "name": null }, { "creator_type": "author", "first_name": "Yi-Teng", "last_name": "Hsiao", "name": null }, { "creator_type": "author", "first_name": "Chia-Lung", "last_name": "Hsieh", "name": null }, { "creator_type": "author", "first_name": "Brian", "last_name": "Abbey", "name": null }, { "creator_type": "author", "first_name": "Alberto", "last_name": "Diaspro", "name": null }, { "creator_type": "author", "first_name": "Aymeric", "last_name": "LeGratiet", "name": null }, { "creator_type": "author", "first_name": "Paolo", "last_name": "Bianchini", "name": null }, { "creator_type": "author", "first_name": "Natan T.", "last_name": "Shaked", "name": null }, { "creator_type": "author", "first_name": "Bertrand", "last_name": "Simon", "name": null }, { "creator_type": "author", "first_name": "Nicolas", "last_name": "Verrier", "name": null }, { "creator_type": "author", "first_name": "Matthieu", "last_name": "Debailleul", "name": null }, { "creator_type": "author", "first_name": "Olivier", "last_name": "Haeberle", "name": null }, { "creator_type": "author", "first_name": "Sheng", "last_name": "Wang", "name": null }, { "creator_type": "author", "first_name": "Mengkun", "last_name": "Liu", "name": null }, { "creator_type": "author", "first_name": "Yeran", "last_name": "Bai", "name": null }, { "creator_type": "author", "first_name": "Ji-Xin", "last_name": "Cheng", "name": null }, { "creator_type": "author", "first_name": "Behjat S.", "last_name": "Kariman", "name": null }, { "creator_type": "author", "first_name": "Katsumasa", "last_name": "Fujita", "name": null }, { "creator_type": "author", "first_name": "Moshe", "last_name": "Sinvani", "name": null }, { "creator_type": "author", "first_name": "Zeev", "last_name": "Zalevsky", "name": null }, { "creator_type": "author", "first_name": "Xiangping", "last_name": "Li", "name": null }, { "creator_type": "author", "first_name": "Guan-Jie", "last_name": "Huang", "name": null }, { "creator_type": "author", "first_name": "Shi-Wei", "last_name": "Chu", "name": null }, { "creator_type": "author", "first_name": "Omer", "last_name": "Tzang", "name": null }, { "creator_type": "author", "first_name": "Dror", "last_name": "Hershkovitz", "name": null }, { "creator_type": "author", "first_name": "Ori", "last_name": "Cheshnovsky", "name": null }, { "creator_type": "author", "first_name": "Mikko J.", "last_name": "Huttunen", "name": null }, { "creator_type": "author", "first_name": "Stefan G.", "last_name": "Stanciu", "name": null }, { "creator_type": "author", "first_name": "Vera N.", "last_name": "Smolyaninova", "name": null }, { "creator_type": "author", "first_name": "Igor I.", "last_name": "Smolyaninov", "name": null }, { "creator_type": "author", "first_name": "Ulf", "last_name": "Leonhardt", "name": null }, { "creator_type": "author", "first_name": "Sahar", "last_name": "Sahebdivan", "name": null }, { "creator_type": "author", "first_name": "Zengbo", "last_name": "Wang", "name": null }, { "creator_type": "author", "first_name": "Boris", "last_name": "Luk'yanchuk", "name": null }, { "creator_type": "author", "first_name": "Limin", "last_name": "Wu", "name": null }, { "creator_type": "author", "first_name": "Alexey V.", "last_name": "Maslov", "name": null }, { "creator_type": "author", "first_name": "Boya", "last_name": "Jin", "name": null }, { "creator_type": "author", "first_name": "Constantin R.", "last_name": "Simovski", "name": null }, { "creator_type": "author", "first_name": "Stephane", "last_name": "Perrin", "name": null }, { "creator_type": "author", "first_name": "Paul", "last_name": "Montgomery", "name": null }, { "creator_type": "author", "first_name": "Sylvain", "last_name": "Lecler", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/lpor.202200029" }, "pmcid": { "normalized": "PMC11178318" }, "pmid": { "normalized": "38883699" } }, "mesh": [], "publication": { "conference_name": null, "date": "2023 Dec", "date_precision": "unknown", "issue": "12", "normalized_date": null, "pages": "2200029", "proceedings_title": null, "publisher": "", "title": "Laser & photonics reviews", "volume": "17", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Roadmap on Label-Free Super-Resolution Imaging.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Background and aims: There has been an increasing role of artificial intelligence (AI) in the characterization of colorectal polyps. Recently, a novel AI algorithm for the characterization of polyps was developed by NEC Corporation (Japan). The aim of our study is to perform an external validation of this algorithm. Methods: The study was a video-based evaluation of the computer-aided diagnosis (CADx) system. Patients undergoing colonoscopy were recruited to record videos of colonic polyps. The frozen polyp images extracted from these videos were used for real-time histological prediction by the endoscopists and by the CADx system, and the results were compared. Results: A total of 115 polyp images were extracted from 66 patients. Sensitivity, negative predictive value and accuracy for diminutive polyps on white light imaging (WLI) and image-enhanced endoscopy (IEE) when assessed by CADx was 90.9% [95% confidence interval (CI) 77.3-100] and 95.8% [95% CI 87.5-100], 80% [95% CI 44.4-97.5] and 90.9% [95% CI 58.7-99.8], 84.8% [95% CI 72.7-97] and 84.6% [95%CI 71.8-94.9], respectively, compared to 48.1% [95%CI 37.7-59.1] and 72% [95% CI 62.5-81], 37.5% [95% CI 28.8-46.8] and 55% [95% CI 44.7-65.0], 53.7% [95% CI 44.2-63.2] and 66.7% [95% CI 59.7-73.3] when assessed by endoscopists. Concordance between histology and CADx-based post-polypectomy surveillance intervals was 93.02% on WLI and 96% on IEE. Conclusion: AI-based optical diagnosis is promising and has the potential to be better than the performance of general endoscopists. We believe that AI can help make real-time optical diagnoses of polyps meeting the Preservation and Incorporation of Valuable endoscopic Innovations standards set by the American Society of Gastrointestinal Endoscopy.", "classifications": [ { "id": "Hamamoto", "label": "Group Hamamoto", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Ejaz", "last_name": "Hossain", "name": null }, { "creator_type": "author", "first_name": "Mohamed", "last_name": "Abdelrahim", "name": null }, { "creator_type": "author", "first_name": "Andrea", "last_name": "Tanasescu", "name": null }, { "creator_type": "author", "first_name": "Masayoshi", "last_name": "Yamada", "name": null }, { "creator_type": "author", "first_name": "Hiroko", "last_name": "Kondo", "name": null }, { "creator_type": "author", "first_name": "Shijemi", "last_name": "Yamada", "name": null }, { "creator_type": "author", "first_name": "Ryuji", "last_name": "Hamamoto", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Marugame", "name": null }, { "creator_type": "author", "first_name": "Yutaka", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Pradeep", "last_name": "Bhandari", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/deo2.178" }, "pmcid": { "normalized": "PMC9614381" }, "pmid": { "normalized": "36320934" } }, "mesh": [], "publication": { "conference_name": null, "date": "2023 Apr", "date_precision": "unknown", "issue": "1", "normalized_date": null, "pages": "e178", "proceedings_title": null, "publisher": "", "title": "DEN open", "volume": "3", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Performance of a novel computer-aided diagnosis system in the characterization of colorectal polyps, and its role in meeting Preservation and Incorporation of Valuable Endoscopic Innovations standards set by the American Society of Gastrointestinal Endoscopy.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Sulfide plays essential roles in controlling various physiological activities in almost all organisms. Although recent evidence has demonstrated that sulfide is endogenously generated and metabolized into polysulfides inside the cells, the relationship between polysulfide metabolism and polysulfide-sensing mechanisms is not well understood. To better define this interplay between polysulfide metabolism and sensing in cells, we investigated the role of polysulfide-metabolizing enzymes such as sulfide:quinone oxidoreductase (SQR) on the temporal dynamics of cellular polysulfide speciation and on the transcriptional regulation by the persulfide-responsive transcription factor SqrR in Rhodobacter capsulatus. We show that disruption of the sqr gene resulted in the loss of SqrR repression by exogenous sulfide at longer culture times, which impacts the speciation of intracellular polysulfides of Deltasqr vs. wild-type strains. Both the attenuated response of SqrR and the change in polysulfide dynamics of the Deltasqr strain is fully reversed by the addition to cells of cystine-derived polysulfides, but not by glutathione disulfide (GSSG)-derived polysulfides. Furthermore, cysteine persulfide (CysSSH) yields a higher rate of oxidation of SqrR relative to glutathione persulfide (GSSH), which leads to DNA dissociation in vitro. The oxidation of SqrR was confirmed by a mass spectrometry-based kinetic profiling strategy that showed distinct polysulfide-crosslinked products obtained with CysSSH vs. GSSH. Taken together, these results establish a novel association between the metabolism of polysulfides and the mechanisms for polysulfide sensing inside the cells.", "classifications": [ { "id": "Akaike", "label": "Group Akaike", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Takayuki", "last_name": "Shimizu", "name": null }, { "creator_type": "author", "first_name": "Tomoaki", "last_name": "Ida", "name": null }, { "creator_type": "author", "first_name": "Giuliano T.", "last_name": "Antelo", "name": null }, { "creator_type": "author", "first_name": "Yuta", "last_name": "Ihara", "name": null }, { "creator_type": "author", "first_name": "Joseph N.", "last_name": "Fakhoury", "name": null }, { "creator_type": "author", "first_name": "Shinji", "last_name": "Masuda", "name": null }, { "creator_type": "author", "first_name": "David P.", "last_name": "Giedroc", "name": null }, { "creator_type": "author", "first_name": "Takaaki", "last_name": "Akaike", "name": null }, { "creator_type": "author", "first_name": "Daiana A.", "last_name": "Capdevila", "name": null }, { "creator_type": "author", "first_name": "Tatsuru", "last_name": "Masuda", "name": null } ], "identifiers": { "doi": { "normalized": "10.1093/pnasnexus/pgad048" }, "pmcid": { "normalized": "PMC9995734" }, "pmid": { "normalized": "36909821" } }, "mesh": [], "publication": { "conference_name": null, "date": "2023 Mar", "date_precision": "unknown", "issue": "3", "normalized_date": null, "pages": "pgad048", "proceedings_title": null, "publisher": "", "title": "PNAS nexus", "volume": "2", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Polysulfide metabolizing enzymes influence SqrR-mediated sulfide-induced transcription by impacting intracellular polysulfide dynamics.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Abstract Background and aims Despite its inclusion in the 11th revision of the International Classification of Diseases, there is a virtual paucity of high-quality scientific evidence about compulsive sexual behavior disorder (CSBD), especially in underrepresented and underserved populations. Therefore, we comprehensively examined CSBD across 42 countries, genders, and sexual orientations, and validated the original (CSBD-19) and short (CSBD-7) versions of the Compulsive Sexual Behavior Disorder Scale to provide standardized, state-of-the-art screening tools for research and clinical practice. Method Using data from the International Sex Survey (N = 82,243; Mage = 32.39 years, SD = 12.52), we evaluated the psychometric properties of the CSBD-19 and CSBD-7 and compared CSBD across 42 countries, three genders, eight sexual orientations, and individuals with low vs. high risk of experiencing CSBD. Results A total of 4.8% of the participants were at high risk of experiencing CSBD. Country- and gender-based differences were observed, while no sexual-orientation-based differences were present in CSBD levels. Only 14% of individuals with CSBD have ever sought treatment for this disorder, with an additional 33% not having sought treatment because of various reasons. Both versions of the scale demonstrated excellent validity and reliability. Discussion and conclusions This study contributes to a better understanding of CSBD in underrepresented and underserved populations and facilitates its identification in diverse populations by providing freely accessible ICD-11-based screening tools in 26 languages. The findings may also serve as a crucial building block to stimulate research into evidence-based, culturally sensitive prevention and intervention strategies for CSBD that are currently missing from the literature.", "classifications": [ { "id": "Fujiwara", "label": "Group Fujiwara", "parent": "Fujiwara", "type": "group" }, { "id": "Fujiwara", "label": "Team Fujiwara", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Beáta", "last_name": "Bőthe", "name": null }, { "creator_type": "author", "first_name": "Mónika", "last_name": "Koós", "name": null }, { "creator_type": "author", "first_name": "Léna", "last_name": "Nagy", "name": null }, { "creator_type": "author", "first_name": "Shane W.", "last_name": "Kraus", "name": null }, { "creator_type": "author", "first_name": "Zsolt", "last_name": "Demetrovics", "name": null }, { "creator_type": "author", "first_name": "Marc N.", "last_name": "Potenza", "name": null }, { "creator_type": "author", "first_name": "Aurélie", "last_name": "Michaud", "name": null }, { "creator_type": "author", "first_name": "Rafael", "last_name": "Ballester-Arnal", "name": null }, { "creator_type": "author", "first_name": "Dominik", "last_name": "Batthyány", "name": null }, { "creator_type": "author", "first_name": "Sophie", "last_name": "Bergeron", "name": null }, { "creator_type": "author", "first_name": "Joël", "last_name": "Billieux", "name": null }, { "creator_type": "author", "first_name": "Peer", "last_name": "Briken", "name": null }, { "creator_type": "author", "first_name": "Julius", "last_name": "Burkauskas", "name": null }, { "creator_type": "author", "first_name": "Georgina", "last_name": "Cárdenas-López", "name": null }, { "creator_type": "author", "first_name": "Joana", "last_name": "Carvalho", "name": null }, { "creator_type": "author", "first_name": "Jesús", "last_name": "Castro-Calvo", "name": null }, { "creator_type": "author", "first_name": "Lijun", "last_name": "Chen", "name": null }, { "creator_type": "author", "first_name": "Giacomo", "last_name": "Ciocca", "name": null }, { "creator_type": "author", "first_name": "Ornella", "last_name": "Corazza", "name": null }, { "creator_type": "author", "first_name": "Rita", "last_name": "Csako", "name": null }, { "creator_type": "author", "first_name": "David P.", "last_name": "Fernandez", "name": null }, { "creator_type": "author", "first_name": "Elaine F.", "last_name": "Fernandez", "name": null }, { "creator_type": "author", "first_name": "Loïs", "last_name": "Fournier", "name": null }, { "creator_type": "author", "first_name": "Hironobu", "last_name": "Fujiwara", "name": null }, { "creator_type": "author", "first_name": "Johannes", "last_name": "Fuss", "name": null }, { "creator_type": "author", "first_name": "Roman", "last_name": "Gabrhelík", "name": null }, { "creator_type": "author", "first_name": "Ateret", "last_name": "Gewirtz-Meydan", "name": null }, { "creator_type": "author", "first_name": "Biljana", "last_name": "Gjoneska", "name": null }, { "creator_type": "author", "first_name": "Mateusz", "last_name": "Gola", "name": null }, { "creator_type": "author", "first_name": "Joshua B.", "last_name": "Grubbs", "name": null }, { "creator_type": "author", "first_name": "Hashim T.", "last_name": "Hashim", "name": null }, { "creator_type": "author", "first_name": "Md Saiful", "last_name": "Islam", "name": null }, { "creator_type": "author", "first_name": "Mustafa", "last_name": "Ismail", "name": null }, { "creator_type": "author", "first_name": "Martha C.", "last_name": "Jiménez-Martínez", "name": null }, { "creator_type": "author", "first_name": "Tanja", "last_name": "Jurin", "name": null }, { "creator_type": "author", "first_name": "Ondrej", "last_name": "Kalina", "name": null }, { "creator_type": "author", "first_name": "Verena", "last_name": "Klein", "name": null }, { "creator_type": "author", "first_name": "András", "last_name": "Költő", "name": null }, { "creator_type": "author", "first_name": "Chih-Ting", "last_name": "Lee", "name": null }, { "creator_type": "author", "first_name": "Sang-Kyu", "last_name": "Lee", "name": null }, { "creator_type": "author", "first_name": "Karol", "last_name": "Lewczuk", "name": null }, { "creator_type": "author", "first_name": "Chung-Ying", "last_name": "Lin", "name": null }, { "creator_type": "author", "first_name": "Christine", "last_name": "Lochner", "name": null }, { "creator_type": "author", "first_name": "Silvia", "last_name": "López-Alvarado", "name": null }, { "creator_type": "author", "first_name": "Kateřina", "last_name": "Lukavská", "name": null }, { "creator_type": "author", "first_name": "Percy", "last_name": "Mayta-Tristán", "name": null }, { "creator_type": "author", "first_name": "Ionut", "last_name": "Milea", "name": null }, { "creator_type": "author", "first_name": "Dan J.", "last_name": "Miller", "name": null }, { "creator_type": "author", "first_name": "Oľga", "last_name": "Orosová", "name": null }, { "creator_type": "author", "first_name": "Gábor", "last_name": "Orosz", "name": null }, { "creator_type": "author", "first_name": "Fernando P.", "last_name": "Ponce", "name": null }, { "creator_type": "author", "first_name": "Gonzalo R.", "last_name": "Quintana", "name": null }, { "creator_type": "author", "first_name": "Gabriel C. Quintero", "last_name": "Garzola", "name": null }, { "creator_type": "author", "first_name": "Jano", "last_name": "Ramos-Diaz", "name": null }, { "creator_type": "author", "first_name": "Kévin", "last_name": "Rigaud", "name": null }, { "creator_type": "author", "first_name": "Ann", "last_name": "Rousseau", "name": null }, { "creator_type": "author", "first_name": "Marco De Tubino", "last_name": "Scanavino", "name": null }, { "creator_type": "author", "first_name": "Marion K.", "last_name": "Schulmeyer", "name": null }, { "creator_type": "author", "first_name": "Pratap", "last_name": "Sharan", "name": null }, { "creator_type": "author", "first_name": "Mami", "last_name": "Shibata", "name": null }, { "creator_type": "author", "first_name": "Sheikh", "last_name": "Shoib", "name": null }, { "creator_type": "author", "first_name": "Vera L. Sigre", "last_name": "Leirós", "name": null }, { "creator_type": "author", "first_name": "Luke", "last_name": "Sniewski", "name": null }, { "creator_type": "author", "first_name": "Ognen", "last_name": "Spasovski", "name": null }, { "creator_type": "author", "first_name": "Vesta", "last_name": "Steibliene", "name": null }, { "creator_type": "author", "first_name": "Dan J.", "last_name": "Stein", "name": null }, { "creator_type": "author", "first_name": "Julian", "last_name": "Strizek", "name": null }, { "creator_type": "author", "first_name": "Aleksandar", "last_name": "Štulhofer", "name": null }, { "creator_type": "author", "first_name": "Berk C.", "last_name": "Ünsal", "name": null }, { "creator_type": "author", "first_name": "Marie-Pier", "last_name": "Vaillancourt-Morel", "name": null } ], "identifiers": { "doi": { "normalized": "10.1556/2006.2023.00028" }, "pmcid": { "normalized": null }, "pmid": { "normalized": null } }, "mesh": [], "publication": { "conference_name": null, "date": "2023/06/22", "date_precision": "unknown", "issue": "aop", "normalized_date": null, "pages": "", "proceedings_title": null, "publisher": "Akadémiai Kiadó", "title": "Journal of Behavioral Addictions", "volume": "-1", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Compulsive sexual behavior disorder in 42 countries: Insights from the International Sex Survey and introduction of standardized assessment tools", "url": "https://akjournals.com/view/journals/2006/aop/article-10.1556-2006.2023.00028/article-10.1556-2006.2023.00028.xml", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Various molecular subclasses of hepatocellular carcinoma (HCC) exists, with many novel cooperating oncogenes and tumor suppressor genes involved in its tumorigenesis. The emerging importance of WNT signaling in HCC has been established. However, the intricate genetic mechanisms involved in this complex signaling pathway remains to be elucidated. Importantly, while some cooperating genes have been identified, there are still many unknown genes associated with catenin beta 1 (CTNNB1)-induced HCC. Mutations in both oncogenes and tumor suppressor genes are required for HCC tumorigenesis. The emergence of the CRISPR/Cas9 system has allowed researchers now to target both alleles efficiently. In this novel study, the Sleeping Beauty transposon system was used as a gene delivery system in vivo to stably integrate an expression cassette that carry pools of gRNAs and overexpress a mutant version of CTNNB1 into the hepatocyte genome. We identified 206 candidate genes that drive HCC tumorigenesis in the context of WNT signaling activation and, neurofibromin 2 (NF2) gene, a known tumor suppressor gene with clinical relevance was validated in this proof-of-principle study.", "classifications": [ { "id": "Yusa", "label": "Group Yusa", "parent": "Eiraku", "type": "group" }, { "id": "Eiraku", "label": "Team Eiraku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Vincent W.", "last_name": "Keng", "name": null }, { "creator_type": "author", "first_name": "Amy P.", "last_name": "Chiu", "name": null }, { "creator_type": "author", "first_name": "Jeffrey C.", "last_name": "To", "name": null }, { "creator_type": "author", "first_name": "Xiao-Xiao", "last_name": "Li", "name": null }, { "creator_type": "author", "first_name": "Michael A.", "last_name": "Linden", "name": null }, { "creator_type": "author", "first_name": "Khalid", "last_name": "Amin", "name": null }, { "creator_type": "author", "first_name": "Branden S.", "last_name": "Moriarity", "name": null }, { "creator_type": "author", "first_name": "Kosuke", "last_name": "Yusa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.heliyon.2023.e18774" }, "pmcid": { "normalized": "PMC10412851" }, "pmid": { "normalized": "37576222" } }, "mesh": [], "publication": { "conference_name": null, "date": "2023 Aug", "date_precision": "unknown", "issue": "8", "normalized_date": null, "pages": "e18774", "proceedings_title": null, "publisher": "", "title": "Heliyon", "volume": "9", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Transposon delivery for CRISPR-based loss-of-function screen in mice identifies NF2 as a cooperating gene involved with the canonical WNT signaling molecular class of hepatocellular carcinoma.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "PURPOSE: This single-center, prospective molecular profiling study characterizes genomic alterations and identifies therapeutic targets in advanced pediatric solid tumors. METHODS: As part of the TOP-GEAR (Trial of Onco-Panel for Gene profiling to Estimate both Adverse events and Response by cancer treatment) project at the National Cancer Center (NCC), Japan, we enrolled pediatric patients with a refractory or recurrent disease during August 2016-December 2021 and performed genomic analysis of matched tumors and blood using originally developed cancer gene panels, NCC Oncopanel (ver. 4.0) and NCC Oncopanel Ped (ver. 1.0). RESULTS: Of 142 patients (age, 1-28 years) enrolled, 128 (90%) were evaluable for genomic analysis; 76 (59%) patients harbored at least one reportable somatic or germline alteration. The tumor samples were collected during the initial diagnosis in 65 (51%) patients, after treatment initiation in 11 (9%) patients, and upon either disease progression or relapse in 52 (41%) patients. The leading altered gene was TP53, followed by MYCN, MYC, CDKN2A, and CDK4. The commonly affected molecular processes were transcription, cell-cycle regulation, epigenetic modifiers, and RAS/mitogen-activated protein kinase signaling. Twelve (9%) patients carried pathogenic germline variants in cancer-predisposing genes. Potentially actionable findings were identified in 40 (31%) patients; to date, 13 (10%) patients have received the recommended therapy on the basis of their genomic profiles. Although four patients had access to targeted therapy through clinical trials, the agents were used in nine patients in an off-label setting. CONCLUSION: The implementation of genomic medicine has furthered our understanding of tumor biology and provided new therapeutic strategies. However, the paucity of proposed agents limits the full potential of actionability, emphasizing the significance of facilitating access to targeted cancer therapies.", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Kayoko", "last_name": "Tao", "name": null }, { "creator_type": "author", "first_name": "Fumito", "last_name": "Yamazaki", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Kubo", "name": null }, { "creator_type": "author", "first_name": "Kuniko", "last_name": "Sunami", "name": null }, { "creator_type": "author", "first_name": "Tadashi", "last_name": "Kumamoto", "name": null }, { "creator_type": "author", "first_name": "Ayumu", "last_name": "Arakawa", "name": null }, { "creator_type": "author", "first_name": "Masanaka", "last_name": "Sugiyama", "name": null }, { "creator_type": "author", "first_name": "Yuko", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Miho", "last_name": "Nakajima", "name": null }, { "creator_type": "author", "first_name": "Nami", "last_name": "Shirakawa", "name": null }, { "creator_type": "author", "first_name": "Kazuki", "last_name": "Tanimura", "name": null }, { "creator_type": "author", "first_name": "Takafumi", "last_name": "Koyama", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Hirata", "name": null }, { "creator_type": "author", "first_name": "Kazuki", "last_name": "Sudo", "name": null }, { "creator_type": "author", "first_name": "Noriko", "last_name": "Tanabe", "name": null }, { "creator_type": "author", "first_name": "Tomoko", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Teruhiko", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Mayuko", "last_name": "Kitami", "name": null }, { "creator_type": "author", "first_name": "Akihiko", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null }, { "creator_type": "author", "first_name": "Yoshiko", "last_name": "Nakano", "name": null }, { "creator_type": "author", "first_name": "Miki", "last_name": "Ohira", "name": null }, { "creator_type": "author", "first_name": "Takehiko", "last_name": "Kamijo", "name": null }, { "creator_type": "author", "first_name": "Atsuko", "last_name": "Nakazawa", "name": null }, { "creator_type": "author", "first_name": "Motohiro", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Koichi", "last_name": "Ichimura", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Kohno", "name": null }, { "creator_type": "author", "first_name": "Noboru", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Tomoro", "last_name": "Hishiki", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Ichikawa", "name": null }, { "creator_type": "author", "first_name": "Chitose", "last_name": "Ogawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1200/po.22.00266" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "37410973" } }, "mesh": [ { "descriptor": "Adolescent", "descriptor_ui": "D000293", "major_topic": false }, { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Child", "descriptor_ui": "D002648", "major_topic": false }, { "descriptor": "Child, Preschool", "descriptor_ui": "D002675", "major_topic": false }, { "descriptor": "Genomics", "descriptor_ui": "D023281", "major_topic": false }, { "descriptor": "Germ-Line Mutation", "descriptor_ui": "D018095", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Infant", "descriptor_ui": "D007223", "major_topic": false }, { "descriptor": "Japan", "descriptor_ui": "D007564", "major_topic": false }, { "descriptor": "Neoplasms", "descriptor_ui": "D009369", "major_topic": true }, { "descriptor": "Precision Medicine", "descriptor_ui": "D057285", "major_topic": true }, { "descriptor": "Young Adult", "descriptor_ui": "D055815", "major_topic": false } ], "publication": { "conference_name": null, "date": "2023 Jul", "date_precision": "unknown", "issue": "", "normalized_date": null, "pages": "e2200266", "proceedings_title": null, "publisher": "", "title": "JCO precision oncology", "volume": "7", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Pediatric Precision Medicine at the National Cancer Center Japan: Prospective Genomic Study of Pediatric Patients with Cancer as Part of the TOP-GEAR Project.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Resistance to immune checkpoint blockade remains challenging in patients with non-small cell lung cancer (NSCLC). Tumor-infiltrating leukocyte (TIL) quantity, composition, and activation status profoundly influence responsiveness to cancer immunotherapy. This study examined the immune landscape in the NSCLC tumor microenvironment by analyzing TIL profiles of 281 fresh resected NSCLC tissues. Unsupervised clustering based on numbers and percentages of 30 TIL types classified adenocarcinoma (LUAD) and squamous cell carcinoma (LUSQ) into the cold, myeloid cell-dominant, and CD8(+) T cell-dominant subtypes. These were significantly correlated with patient prognosis; the myeloid cell subtype had worse outcomes than the others. Integrated genomic and transcriptomic analyses, including RNA sequencing, whole-exome sequencing, T-cell receptor repertoire, and metabolomics of tumor tissue, revealed that immune reaction-related signaling pathways were inactivated, while the glycolysis and K-ras signaling pathways activated in LUAD and LUSQ myeloid cell subtypes. Cases with ALK and ROS1 fusion genes were enriched in the LUAD myeloid subtype, and the frequency of TERT copy-number variations was higher in LUSQ myeloid subtype than in the others. These classifications of NSCLC based on TIL status may be useful for developing personalized immune therapies for NSCLC. SIGNIFICANCE: The precise TIL profiling classified NSCLC into novel three immune subtypes that correlates with patient outcome, identifying subtype-specific molecular pathways and genomic alterations that should play important roles in constructing subtype-specific immune tumor microenvironments. These classifications of NSCLC based on TIL status are useful for developing personalized immune therapies for NSCLC.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Kazunori", "last_name": "Aoki", "name": null }, { "creator_type": "author", "first_name": "Yukari", "last_name": "Nishito", "name": null }, { "creator_type": "author", "first_name": "Noriko", "last_name": "Motoi", "name": null }, { "creator_type": "author", "first_name": "Yasuhito", "last_name": "Arai", "name": null }, { "creator_type": "author", "first_name": "Nobuyoshi", "last_name": "Hiraoka", "name": null }, { "creator_type": "author", "first_name": "Tatsuhiro", "last_name": "Shibata", "name": null }, { "creator_type": "author", "first_name": "Yukiko", "last_name": "Sonobe", "name": null }, { "creator_type": "author", "first_name": "Yoko", "last_name": "Kayukawa", "name": null }, { "creator_type": "author", "first_name": "Eri", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Mina", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Etsuko", "last_name": "Fujii", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Nishizawa", "name": null }, { "creator_type": "author", "first_name": "Hironori", "last_name": "Fukuda", "name": null }, { "creator_type": "author", "first_name": "Kana", "last_name": "Ohashi", "name": null }, { "creator_type": "author", "first_name": "Kosuke", "last_name": "Arai", "name": null }, { "creator_type": "author", "first_name": "Yukihiro", "last_name": "Mizoguchi", "name": null }, { "creator_type": "author", "first_name": "Yukihiro", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Shun-Ichi", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Makiko", "last_name": "Yamashita", "name": null }, { "creator_type": "author", "first_name": "Shigehisa", "last_name": "Kitano", "name": null }, { "creator_type": "author", "first_name": "Hiromi", "last_name": "Sakamoto", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Nagata", "name": null }, { "creator_type": "author", "first_name": "Risa", "last_name": "Mitsumori", "name": null }, { "creator_type": "author", "first_name": "Kouichi", "last_name": "Ozaki", "name": null }, { "creator_type": "author", "first_name": "Shumpei", "last_name": "Niida", "name": null }, { "creator_type": "author", "first_name": "Yae", "last_name": "Kanai", "name": null }, { "creator_type": "author", "first_name": "Akiyoshi", "last_name": "Hirayama", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Toru", "last_name": "Maruyama", "name": null }, { "creator_type": "author", "first_name": "Keisuke", "last_name": "Tsukada", "name": null }, { "creator_type": "author", "first_name": "Nami", "last_name": "Yabuki", "name": null }, { "creator_type": "author", "first_name": "Mei", "last_name": "Shimada", "name": null }, { "creator_type": "author", "first_name": "Takehisa", "last_name": "Kitazawa", "name": null }, { "creator_type": "author", "first_name": "Osamu", "last_name": "Natori", "name": null }, { "creator_type": "author", "first_name": "Noriaki", "last_name": "Sawada", "name": null }, { "creator_type": "author", "first_name": "Atsuhiko", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Teruhiko", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Kazuki", "last_name": "Yasuda", "name": null }, { "creator_type": "author", "first_name": "Hideaki", "last_name": "Mizuno", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Tsunoda", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Ochiai", "name": null } ], "identifiers": { "doi": { "normalized": "10.1158/2767-9764.crc-22-0415" }, "pmcid": { "normalized": "PMC10263066" }, "pmid": { "normalized": "37377611" } }, "mesh": [ { "descriptor": "Carcinoma, Non-Small-Cell Lung", "descriptor_ui": "D002289", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Lung Neoplasms", "descriptor_ui": "D008175", "major_topic": true }, { "descriptor": "Lymphocytes, Tumor-Infiltrating", "descriptor_ui": "D016246", "major_topic": false }, { "descriptor": "Protein-Tyrosine Kinases", "descriptor_ui": "D011505", "major_topic": false }, { "descriptor": "Proto-Oncogene Proteins", "descriptor_ui": "D011518", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Tumor Microenvironment", "descriptor_ui": "D059016", "major_topic": false } ], "publication": { "conference_name": null, "date": "2023 Jun", "date_precision": "unknown", "issue": "6", "normalized_date": null, "pages": "1026-1040", "proceedings_title": null, "publisher": "", "title": "Cancer research communications", "volume": "3", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Tumor-infiltrating Leukocyte Profiling Defines Three Immune Subtypes of NSCLC with Distinct Signaling Pathways and Genetic Alterations.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Muscle satellite cells (MuSCs), myogenic stem cells in skeletal muscles, play an essential role in muscle regeneration. After skeletal muscle injury, quiescent MuSCs are activated to enter the cell cycle and proliferate, thereby initiating regeneration; however, the mechanisms that ensure successful MuSC division, including chromosome segregation, remain unclear. Here, we show that PIEZO1, a calcium ion (Ca(2+))-permeable cation channel activated by membrane tension, mediates spontaneous Ca(2+) influx to control the regenerative function of MuSCs. Our genetic engineering approach in mice revealed that PIEZO1 is functionally expressed in MuSCs and that Piezo1 deletion in these cells delays myofibre regeneration after injury. These results are, at least in part, due to a mitotic defect in MuSCs. Mechanistically, this phenotype is caused by impaired PIEZO1-Rho signalling during myogenesis. Thus, we provide the first concrete evidence that PIEZO1, a bona fide mechanosensitive ion channel, promotes proliferation and regenerative functions of MuSCs through precise control of cell division.", "classifications": [ { "id": "Shintaku", "label": "Group Shintaku", "parent": "Shintaku", "type": "group" }, { "id": "Shintaku", "label": "Team Shintaku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Kotaro", "last_name": "Hirano", "name": null }, { "creator_type": "author", "first_name": "Masaki", "last_name": "Tsuchiya", "name": null }, { "creator_type": "author", "first_name": "Akifumi", "last_name": "Shiomi", "name": null }, { "creator_type": "author", "first_name": "Seiji", "last_name": "Takabayashi", "name": null }, { "creator_type": "author", "first_name": "Miki", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Yudai", "last_name": "Ishikawa", "name": null }, { "creator_type": "author", "first_name": "Yuya", "last_name": "Kawano", "name": null }, { "creator_type": "author", "first_name": "Yutaka", "last_name": "Takabayashi", "name": null }, { "creator_type": "author", "first_name": "Kaori", "last_name": "Nishikawa", "name": null }, { "creator_type": "author", "first_name": "Kohjiro", "last_name": "Nagao", "name": null }, { "creator_type": "author", "first_name": "Eiji", "last_name": "Umemoto", "name": null }, { "creator_type": "author", "first_name": "Yasuo", "last_name": "Kitajima", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Ono", "name": null }, { "creator_type": "author", "first_name": "Keiko", "last_name": "Nonomura", "name": null }, { "creator_type": "author", "first_name": "Hirofumi", "last_name": "Shintaku", "name": null }, { "creator_type": "author", "first_name": "Yasuo", "last_name": "Mori", "name": null }, { "creator_type": "author", "first_name": "Masato", "last_name": "Umeda", "name": null }, { "creator_type": "author", "first_name": "Yuji", "last_name": "Hara", "name": null } ], "identifiers": { "doi": { "normalized": "10.26508/lsa.202201783" }, "pmcid": { "normalized": "PMC9711862" }, "pmid": { "normalized": "36446523" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Chromosome Segregation", "descriptor_ui": "D020090", "major_topic": false }, { "descriptor": "Ion Channels", "descriptor_ui": "D007473", "major_topic": true }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Muscle, Skeletal", "descriptor_ui": "D018482", "major_topic": false }, { "descriptor": "Myoblasts", "descriptor_ui": "D032446", "major_topic": false }, { "descriptor": "Regeneration", "descriptor_ui": "D012038", "major_topic": true }, { "descriptor": "Satellite Cells, Skeletal Muscle", "descriptor_ui": "D032496", "major_topic": true }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false } ], "publication": { "conference_name": null, "date": "2023 Feb", "date_precision": "unknown", "issue": "2", "normalized_date": null, "pages": "", "proceedings_title": null, "publisher": "", "title": "Life science alliance", "volume": "6", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "The mechanosensitive ion channel PIEZO1 promotes satellite cell function in muscle regeneration.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Earlier studies revealed the presence of cysteine persulfide (CysSSH) and related polysulfide species in various mammalian tissues. CysSSH has both antioxidant and oxidant properties, modulates redox-dependent signal transduction and has been shown to mitigate oxidative stress. However, its functional relevance in the setting of myocardial ischaemia-reperfusion injury (IRI) remains unknown. The present study was undertaken to (1) study the dynamics of production and consumption of persulfides under normoxic and hypoxic conditions in the heart, and (2) determine whether exogenous administration of the CysSSH donor, cysteine trisulfide (Cys-SSS-Cys) at the onset of reperfusion rescues functional impairment and myocardial damage by interfering with lipid peroxidation. Utilising a well-established ex vivo Langendorff murine model, we here demonstrate that endogenous tissue concentrations of CysSSH are upregulated when oxygen supply is compromised (global myocardial ischaemia) and rapidly restored to baseline levels upon reperfusion, suggestive of active regulation. In a separate set of experiments, exogenous administration of Cys-SSS-Cys for 10 min at the onset of reperfusion was found to decrease malondialdehyde (MDA) concentrations, formation of 4-hydroxynonenal (4-HNE) protein adducts and rescue the heart from injury. Cys-SSS-Cys also restored post-ischaemic cardiac function, improving both coronary flow and left ventricular developed pressure (LVDP). Taken together, these results support the notion that endogenous CysSSH plays an important role as a “redox preconditioning” agent to combat the oxidative insult in myocardial IRI.", "classifications": [ { "id": "JPMJCR2024", "label": "JPMJCR2024", "researcher": "Motohiro Nishida", "type": "grant" }, { "id": "Akaike", "label": "Group Akaike", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Group Nishida", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Kayleigh", "last_name": "Griffiths", "name": null }, { "creator_type": "author", "first_name": "Tomoaki", "last_name": "Ida", "name": null }, { "creator_type": "author", "first_name": "Masanobu", "last_name": "Morita", "name": null }, { "creator_type": "author", "first_name": "Reece J.", "last_name": "Lamb", "name": null }, { "creator_type": "author", "first_name": "Jordan J.", "last_name": "Lee", "name": null }, { "creator_type": "author", "first_name": "Michael P.", "last_name": "Frenneaux", "name": null }, { "creator_type": "author", "first_name": "Jon M.", "last_name": "Fukuto", "name": null }, { "creator_type": "author", "first_name": "Takaaki", "last_name": "Akaike", "name": null }, { "creator_type": "author", "first_name": "Martin", "last_name": "Feelisch", "name": null }, { "creator_type": "author", "first_name": "Melanie", "last_name": "Madhani", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.redox.2023.102605" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "36657187" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cysteine", "descriptor_ui": "D003545", "major_topic": false }, { "descriptor": "Ischemic Preconditioning", "descriptor_ui": "D019194", "major_topic": true }, { "descriptor": "Ischemic Preconditioning, Myocardial", "descriptor_ui": "D019157", "major_topic": true }, { "descriptor": "Lipid Peroxidation", "descriptor_ui": "D015227", "major_topic": false }, { "descriptor": "Mammals", "descriptor_ui": "D008322", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Myocardial Reperfusion Injury", "descriptor_ui": "D015428", "major_topic": true }, { "descriptor": "Myocardium", "descriptor_ui": "D009206", "major_topic": false }, { "descriptor": "Sulfides", "descriptor_ui": "D013440", "major_topic": false } ], "publication": { "conference_name": null, "date": "2023 Apr", "date_precision": "unknown", "issue": "", "normalized_date": null, "pages": "", "proceedings_title": null, "publisher": "", "title": "Redox Biology", "volume": "60", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "Cysteine hydropersulfide reduces lipid peroxidation and protects against myocardial ischaemia-reperfusion injury - Are endogenous persulfides mediators of ischaemic preconditioning?", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Cancer‑associated fibroblasts (CAFs) are implicated in the strong malignancy of pancreatic cancer (PC). Various CAF subtypes have different functions, and their heterogeneity likely influence the malignancy of PC. Meanwhile, it is known that senescent cells can create a tumor‑promoting microenvironment by inducing a senescence‑associated secretory phenotype (SASP). In the present study, the effects of individual differences in CAFs on PC malignancy were investigated with a focus on cellular senescence. First, primary cultures of CAFs from 8 PC patients were generated and co‑cultured with PC cell lines. This co‑culture assay showed that differences in CAFs induce differences in PC cell proliferation. It was further investigated which clinical factors affected the malignant potential of CAF and it was found that the difference of malignant potential of each CAF was marginally related to the age of original patients. Next, to verify the senescence of CAFs really affected the malignant potential of CAF, PCR array analysis of each CAF sample was performed and it was revealed that expression of genes about cellular senescence and SASP such as tumor protein p53, nuclear factor kappa B subunit 1, and IL6, are related to the malignant potential of CAFs impacting on PC proliferation. Finally, to elucidate the effect of p53‑mediated cellular senescence of CAFs on malignant potential of PC, it was examined whether CAFs with the treatment of p53 inhibitor affected PC cell proliferation in co‑culture assays. The treatment of CAFs with p53 inhibitor significantly suppressed PC cell proliferation. In addition, a comparison of the concentration of IL‑6, a SASP cytokine, in the co‑culture supernatant showed a significant decrease in the sample after p53 inhibitor treatment. In conclusion, the present results suggested that proliferation potential of PC may be related to p53‑mediated cellular senescence and SASP of CAFs.", "classifications": [ { "id": "Yamamoto", "label": "Group Yamamoto", "parent": "Toyoshima", "type": "group" }, { "id": "Toyoshima", "label": "Team Toyoshima", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Masaya", "last_name": "Higashiguchi", "name": null }, { "creator_type": "author", "first_name": "Hirotomo", "last_name": "Murakami", "name": null }, { "creator_type": "author", "first_name": "Hirofumi", "last_name": "Akita", "name": null }, { "creator_type": "author", "first_name": "Shogo", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Shokichi", "last_name": "Takahama", "name": null }, { "creator_type": "author", "first_name": "Yoshifumi", "last_name": "Iwagami", "name": null }, { "creator_type": "author", "first_name": "Daisaku", "last_name": "Yamada", "name": null }, { "creator_type": "author", "first_name": "Yoshito", "last_name": "Tomimaru", "name": null }, { "creator_type": "author", "first_name": "Takehiro", "last_name": "Noda", "name": null }, { "creator_type": "author", "first_name": "Kunihito", "last_name": "Gotoh", "name": null }, { "creator_type": "author", "first_name": "Yuichiro", "last_name": "Doki", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Hidetoshi", "last_name": "Eguchi", "name": null } ], "identifiers": { "doi": { "normalized": "10.3892/or.2023.8535" }, "pmcid": { "normalized": "PMC10091076" }, "pmid": { "normalized": "36999632" } }, "mesh": [ { "descriptor": "Cancer-Associated Fibroblasts", "descriptor_ui": "D000072645", "major_topic": true }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Cellular Senescence", "descriptor_ui": "D016922", "major_topic": false }, { "descriptor": "Fibroblasts", "descriptor_ui": "D005347", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Pancreatic Neoplasms", "descriptor_ui": "D010190", "major_topic": true }, { "descriptor": "Phenotype", "descriptor_ui": "D010641", "major_topic": false }, { "descriptor": "Senescence-Associated Secretory Phenotype", "descriptor_ui": "D000089262", "major_topic": false }, { "descriptor": "Tumor Microenvironment", "descriptor_ui": "D059016", "major_topic": false }, { "descriptor": "Tumor Suppressor Protein p53", "descriptor_ui": "D016159", "major_topic": false } ], "publication": { "conference_name": null, "date": "2023 May", "date_precision": "unknown", "issue": "5", "normalized_date": null, "pages": "98", "proceedings_title": null, "publisher": "", "title": "Oncology reports", "volume": "49", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "The impact of cellular senescence and senescence‑associated secretory phenotype in cancer‑associated fibroblasts on the malignancy of pancreatic cancer.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Cell division is essential for development and involves spindle assembly, chromosome separation, and cytokinesis. In plants, the genetic tools for controlling the events in cell division at the desired time are limited and ineffective owing to high redundancy and lethality. Therefore, we screened cell division-affecting compounds in Arabidopsis thaliana zygotes, whose cell division is traceable without time-lapse observations. We then determined the target events of the identified compounds using live-cell imaging of tobacco BY-2 cells. Subsequently, we isolated two compounds, PD-180970 and PP2, neither of which caused lethal damage. PD-180970 disrupted microtubule (MT) organization and, thus, nuclear separation, and PP2 blocked phragmoplast formation and impaired cytokinesis. Phosphoproteomic analysis showed that these compounds reduced the phosphorylation of diverse proteins, including MT-associated proteins (MAP70) and class II Kinesin-12. Moreover, these compounds were effective in multiple plant species, such as cucumber (Cucumis sativus) and moss (Physcomitrium patens). These properties make PD-180970 and PP2 useful tools for transiently controlling plant cell division at key manipulation nodes conserved across diverse plant species.", "classifications": [ { "id": "JPMJCR2121", "label": "JPMJCR2121", "researcher": "Minako Ueda", "type": "grant" }, { "id": "Ueda", "label": "Group Ueda", "parent": "Ueda", "type": "group" }, { "id": "Ueda", "label": "Team Ueda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yusuke", "last_name": "Kimata", "name": null }, { "creator_type": "author", "first_name": "Moe", "last_name": "Yamada", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Murata", "name": null }, { "creator_type": "author", "first_name": "Keiko", "last_name": "Kuwata", "name": null }, { "creator_type": "author", "first_name": "Ayato", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Takamasa", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Kurihara", "name": null }, { "creator_type": "author", "first_name": "Mitsuyasu", "last_name": "Hasebe", "name": null }, { "creator_type": "author", "first_name": "Tetsuya", "last_name": "Higashiyama", "name": null }, { "creator_type": "author", "first_name": "Minako", "last_name": "Ueda", "name": null } ], "identifiers": { "doi": { "normalized": "10.26508/lsa.202201657" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "36849250" } }, "mesh": [ { "descriptor": "Arabidopsis", "descriptor_ui": "D017360", "major_topic": true }, { "descriptor": "Cell Division", "descriptor_ui": "D002455", "major_topic": false }, { "descriptor": "Chromosome Segregation", "descriptor_ui": "D020090", "major_topic": false }, { "descriptor": "Cytokinesis", "descriptor_ui": "D048749", "major_topic": true }, { "descriptor": "Microtubule-Associated Proteins", "descriptor_ui": "D008869", "major_topic": false }, { "descriptor": "Microtubules", "descriptor_ui": "D008870", "major_topic": false } ], "publication": { "conference_name": null, "date": "2023 May", "date_precision": "unknown", "issue": "5", "normalized_date": null, "pages": "e202201657", "proceedings_title": null, "publisher": "", "title": "Life science alliance", "volume": "6", "year": 2023 }, "ssbd": { "database": [ "ssbd-database-000293" ], "repository": [ "ssbd-repos-000293" ] }, "title": "Novel inhibitors of microtubule organization and phragmoplast formation in diverse plant species.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "SARS-CoV-2 induces severe organ damage not only in the lung but also in the liver, heart, kidney, and intestine. It is known that COVID-19 severity correlates with liver dysfunction, but few studies have investigated the liver pathophysiology in COVID-19 patients. Here, we elucidated liver pathophysiology in COVID-19 patients using organs-on-a-chip technology and clinical analyses. First, we developed liver-on-a-chip (LoC) which recapitulating hepatic functions around the intrahepatic bile duct and blood vessel. We found that hepatic dysfunctions, but not hepatobiliary diseases, were strongly induced by SARS-CoV-2 infection. Next, we evaluated the therapeutic effects of COVID-19 drugs to inhibit viral replication and recover hepatic dysfunctions, and found that the combination of anti-viral and immunosuppressive drugs (Remdesivir and Baricitinib) is effective to treat hepatic dysfunctions caused by SARS-CoV-2 infection. Finally, we analyzed the sera obtained from COVID-19 patients, and revealed that COVID-19 patients, who were positive for serum viral RNA, are likely to become severe and develop hepatic dysfunctions, as compared with COVID-19 patients who were negative for serum viral RNA. We succeeded in modeling the liver pathophysiology of COVID-19 patients using LoC technology and clinical samples.", "classifications": [ { "id": "Yamamoto", "label": "Group Yamamoto", "parent": "Toyoshima", "type": "group" }, { "id": "Toyoshima", "label": "Team Toyoshima", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Sayaka", "last_name": "Deguchi", "name": null }, { "creator_type": "author", "first_name": "Kaori", "last_name": "Kosugi", "name": null }, { "creator_type": "author", "first_name": "Rina", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Ayaka", "last_name": "Sakamoto", "name": null }, { "creator_type": "author", "first_name": "Masaki", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Rafal P.", "last_name": "Krol", "name": null }, { "creator_type": "author", "first_name": "Peter", "last_name": "Gee", "name": null }, { "creator_type": "author", "first_name": "Ryosuke", "last_name": "Negoro", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Noda", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Yu-Suke", "last_name": "Torisawa", "name": null }, { "creator_type": "author", "first_name": "Miki", "last_name": "Nagao", "name": null }, { "creator_type": "author", "first_name": "Kazuo", "last_name": "Takayama", "name": null } ], "identifiers": { "doi": { "normalized": "10.1093/pnasnexus/pgad029" }, "pmcid": { "normalized": "PMC9991504" }, "pmid": { "normalized": "36896132" } }, "mesh": [], "publication": { "conference_name": null, "date": "2023 Mar", "date_precision": "unknown", "issue": "3", "normalized_date": null, "pages": "pgad029", "proceedings_title": null, "publisher": "", "title": "PNAS nexus", "volume": "2", "year": 2023 }, "ssbd": { "database": [ "ssbd-database-000291" ], "repository": [ "ssbd-repos-000291" ] }, "title": "Elucidation of the liver pathophysiology of COVID-19 patients using liver-on-a-chips.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "High-quality, straightforward single-cell RNA sequencing (RNA-seq) with spatial resolution remains challenging. Here, we developed DRaqL (direct RNA recovery and quenching for laser capture microdissection), an experimental approach for efficient cell lysis of tissue sections, directly applicable to cDNA amplification. Single-cell RNA-seq combined with DRaqL allowed transcriptomic profiling from alcohol-fixed sections with efficiency comparable with that of profiling from freshly dissociated cells, together with effective exon-exon junction profiling. The combination of DRaqL with protease treatment enabled robust and efficient single-cell transcriptome analysis from formalin-fixed tissue sections. Applying this method to mouse ovarian sections, we were able to predict the transcriptome of oocytes by their size and identified an anomaly in the size-transcriptome relationship relevant to growth retardation of oocytes, in addition to detecting oocyte-specific splice isoforms. Furthermore, we identified differentially expressed genes in granulosa cells in association with their proximity to the oocytes, suggesting distinct epigenetic regulations and cell-cycle activities governing the germ-soma relationship. Thus, DRaqL is a versatile, efficient approach for high-quality single-cell RNA-seq from tissue sections, thereby revealing histological heterogeneity in folliculogenic transcriptome.", "classifications": [ { "id": "Yamamoto", "label": "Group Yamamoto", "parent": "Toyoshima", "type": "group" }, { "id": "Toyoshima", "label": "Team Toyoshima", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Hiroki", "last_name": "Ikeda", "name": null }, { "creator_type": "author", "first_name": "Shintaro", "last_name": "Miyao", "name": null }, { "creator_type": "author", "first_name": "So", "last_name": "Nagaoka", "name": null }, { "creator_type": "author", "first_name": "Tomoya", "last_name": "Takashima", "name": null }, { "creator_type": "author", "first_name": "Sze-Ming", "last_name": "Law", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Kazuki", "last_name": "Kurimoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.26508/lsa.202301929" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "37722727" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Cycle", "descriptor_ui": "D002453", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Gene Expression Profiling", "descriptor_ui": "D020869", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Oocytes", "descriptor_ui": "D009865", "major_topic": false }, { "descriptor": "Ovary", "descriptor_ui": "D010053", "major_topic": true }, { "descriptor": "Transcriptome", "descriptor_ui": "D059467", "major_topic": true } ], "publication": { "conference_name": null, "date": "2023 Nov", "date_precision": "unknown", "issue": "11", "normalized_date": null, "pages": "e202301929", "proceedings_title": null, "publisher": "", "title": "Life science alliance", "volume": "6", "year": 2023 }, "ssbd": { "database": [], "repository": [] }, "title": "High-quality single-cell transcriptomics from ovarian histological sections during folliculogenesis.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "A high-salt diet significantly impacts various diseases, including cancer and immune diseases. Recent studies suggest that the high-salt/hyperosmotic environment in the body may alter the chronic properties of cancer and immune cells in the disease context. However, little is known about the acute metabolic changes in hyperosmotic stress. Here, we found that hyperosmotic stress for a few minutes induces Warburg-like metabolic remodeling in HeLa and Raw264.7 cells and suppresses fatty acid oxidation. Regarding Warburg-like remodeling, we determined that the pyruvate dehydrogenase (PDH) phosphorylation status was altered bidirectionally (high in hyperosmolarity and low in hypoosmolarity) to osmotic stress in isolated mitochondria, suggesting that mitochondria themselves have an acute osmo-sensing mechanism. Additionally, we demonstrate that Warburg-like remodeling is required for HeLa cells to maintain ATP levels and survive under hyperosmotic conditions. Collectively, our findings suggest that cells exhibit acute metabolic remodeling under osmotic stress via the regulation of PDH phosphorylation by direct osmosensing within mitochondria.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Takeshi", "last_name": "Ikizawa", "name": null }, { "creator_type": "author", "first_name": "Kazutaka", "last_name": "Ikeda", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Arita", "name": null }, { "creator_type": "author", "first_name": "Shojiro", "last_name": "Kitajima", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Hidenori", "last_name": "Ichijo", "name": null }, { "creator_type": "author", "first_name": "Isao", "last_name": "Naguro", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.jbc.2022.102837" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "36581206" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "HeLa Cells", "descriptor_ui": "D006367", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mitochondria", "descriptor_ui": "D008928", "major_topic": true }, { "descriptor": "Osmotic Pressure", "descriptor_ui": "D009997", "major_topic": true }, { "descriptor": "Oxidoreductases", "descriptor_ui": "D010088", "major_topic": true }, { "descriptor": "Phosphorylation", "descriptor_ui": "D010766", "major_topic": false }, { "descriptor": "Pyruvates", "descriptor_ui": "D011773", "major_topic": true }, { "descriptor": "RAW 264.7 Cells", "descriptor_ui": "D000067996", "major_topic": false } ], "publication": { "conference_name": null, "date": "2022 Dec 26", "date_precision": "day", "issue": "", "normalized_date": "2022-12-26", "pages": "102837", "proceedings_title": null, "publisher": "", "title": "The Journal of biological chemistry", "volume": "", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Mitochondria directly sense osmotic stress to trigger rapid metabolic remodeling via regulation of pyruvate dehydrogenase (PDH) phosphorylation.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The segmented body plan of vertebrates is established during somitogenesis, a well-studied process in model organisms, but remains largely elusive in humans due to ethical and technical limitations. Despite recent advances with pluripotent stem cell (PSC)-based approaches(1-5), models that robustly recapitulate human somitogenesis in both space and time are still largely missing. Here, we introduce a PSC-derived mesoderm-based 3D model of human segmentation and somitogenesis, which we termed 'axioloid', that captures accurately the oscillatory dynamics of the segmentation clock and the morphological and molecular characteristics of sequential somite formation in vitro. Axioloids show proper rostrocaudal patterning of forming segments and robust anterior-posterior FGF/WNT signaling gradients and retinoic acid (RA) signaling components. We identify an unexpected critical role of RA signaling in the stabilization of forming segments, indicating distinct, but also synergistic effects of RA and extracellular matrix (ECM) on the formation and epithelialization of somites. Importantly, comparative analysis demonstrates striking similarities of axioloids to the human embryo, further validated by the presence of a HOX code in axioloids. Lastly, we demonstrate the utility of axioloids to study the pathogenesis of human congenital spine diseases, by using patient-like iPSCs with mutations in HES7 and MESP2. These results suggest that axioloids represent a promising novel platform to study axial development and disease in humans.", "classifications": [ { "id": "Yamamoto", "label": "Group Yamamoto", "parent": "Toyoshima", "type": "group" }, { "id": "Toyoshima", "label": "Team Toyoshima", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yoshihiro", "last_name": "Yamanaka", "name": null }, { "creator_type": "author", "first_name": "Sofiane", "last_name": "Hamidi", "name": null }, { "creator_type": "author", "first_name": "Kumiko", "last_name": "Yoshioka-Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Sirajam", "last_name": "Munira", "name": null }, { "creator_type": "author", "first_name": "Kazunori", "last_name": "Sunadome", "name": null }, { "creator_type": "author", "first_name": "Yi", "last_name": "Zhang", "name": null }, { "creator_type": "author", "first_name": "Yuzuru", "last_name": "Kurokawa", "name": null }, { "creator_type": "author", "first_name": "Rolf", "last_name": "Ericsson", "name": null }, { "creator_type": "author", "first_name": "Ai", "last_name": "Mieda", "name": null }, { "creator_type": "author", "first_name": "Jamie L.", "last_name": "Thompson", "name": null }, { "creator_type": "author", "first_name": "Janet", "last_name": "Kerwin", "name": null }, { "creator_type": "author", "first_name": "Steven", "last_name": "Lisgo", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Naomi", "last_name": "Moris", "name": null }, { "creator_type": "author", "first_name": "Alfonso", "last_name": "Martinez-Arias", "name": null }, { "creator_type": "author", "first_name": "Taro", "last_name": "Tsujimura", "name": null }, { "creator_type": "author", "first_name": "Cantas", "last_name": "Alev", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41586-022-05649-2" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "36543322" } }, "mesh": [ { "descriptor": "Basic Helix-Loop-Helix Proteins", "descriptor_ui": "D051792", "major_topic": false }, { "descriptor": "Body Patterning", "descriptor_ui": "D019521", "major_topic": true }, { "descriptor": "Cell Culture Techniques, Three Dimensional", "descriptor_ui": "D000087603", "major_topic": true }, { "descriptor": "Extracellular Matrix", "descriptor_ui": "D005109", "major_topic": false }, { "descriptor": "Fibroblast Growth Factors", "descriptor_ui": "D005346", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "In Vitro Techniques", "descriptor_ui": "D066298", "major_topic": false }, { "descriptor": "Induced Pluripotent Stem Cells", "descriptor_ui": "D057026", "major_topic": false }, { "descriptor": "Models, Biological", "descriptor_ui": "D008954", "major_topic": false }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": false }, { "descriptor": "Somites", "descriptor_ui": "D019170", "major_topic": true }, { "descriptor": "Spinal Diseases", "descriptor_ui": "D013122", "major_topic": false }, { "descriptor": "Tretinoin", "descriptor_ui": "D014212", "major_topic": false }, { "descriptor": "Wnt Signaling Pathway", "descriptor_ui": "D060449", "major_topic": false } ], "publication": { "conference_name": null, "date": "2022 Dec 21", "date_precision": "day", "issue": "", "normalized_date": "2022-12-21", "pages": "", "proceedings_title": null, "publisher": "", "title": "Nature", "volume": "", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Reconstituting human somitogenesis in vitro.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "OBJECTIVES: To compare fluorescein tear break-up time (BUT) and noninvasive BUT measured using interferometry and corneal topography. METHODS: We investigated 34 eyes of 34 patients with dry eye (mean age 39.2+/-8.3 years) and 16 eyes of 16 non-dry eye subjects (33.5+/-6.5 years). Tear film stability was measured using fluorescein BUT, noninvasive BUT (NIBUT)-DR1 with an interferometer, and noninvasive keratographic BUT (NIKBUT)-first and average using corneal topography. Correlations between fluorescein BUT and noninvasive BUT parameters were determined statistically. The noninvasive BUTs were compared between the dry eye and non-dry eye groups. The agreement between fluorescein and noninvasive BUTs was described using Bland-Altman analysis. RESULTS: Fluorescein BUT was significantly correlated with NIBUT-DR1, NIKBUT-first, and NIKBUT-average. The Bland-Altman analysis revealed bias and 95% limits of agreement between fluorescein BUT and noninvasive BUTs as follows: NIBUT-DR1: 2.07 s, -5.33 to 9.46 s; NIKBUT-first: 3.39 s, -5.46 to 12.24 s; NIKBUT-average: 6.61 s, -1.58 to 14.79 s. The noninvasive BUTs were significantly different between the two groups. When NIBUT-DR1, NIKBUT-first, and NIKBUT-average with Bland-Altman correction were used as an index for dry eye, the cut-off values were 7.1, 8.4, and 11.6 s, respectively. The sensitivities were 0.735, 0.818, and 0.727 and specificities were 0.500, 0.437, and 0.562, respectively. CONCLUSION: Fluorescein BUT and noninvasive BUTs were significantly correlated, and noninvasive BUTs had higher values than fluorescein BUT. Considering the differences between fluorescein BUT and noninvasive BUTs, noninvasive methods can be used as effective tool for diagnosing dry eye.", "classifications": [ { "id": "Suzuki", "label": "Group Suzuki", "parent": "Takekawa", "type": "group" }, { "id": "Takekawa", "label": "Team Takekawa", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Takashi", "last_name": "Itokawa", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Shizuka", "last_name": "Koh", "name": null }, { "creator_type": "author", "first_name": "Yuichi", "last_name": "Hori", "name": null } ], "identifiers": { "doi": { "normalized": "10.1097/icl.0000000000000966" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "36548980" } }, "mesh": [ { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Corneal Topography", "descriptor_ui": "D019781", "major_topic": false }, { "descriptor": "Dry Eye Syndromes", "descriptor_ui": "D015352", "major_topic": true }, { "descriptor": "Fluorescein", "descriptor_ui": "D019793", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Interferometry", "descriptor_ui": "D007368", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Tears", "descriptor_ui": "D013666", "major_topic": false } ], "publication": { "conference_name": null, "date": "2022 Dec 20", "date_precision": "day", "issue": "", "normalized_date": "2022-12-20", "pages": "", "proceedings_title": null, "publisher": "", "title": "Eye & contact lens", "volume": "", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Evaluating the Differences Between Fluorescein Tear Break-up Time and Noninvasive Measurement Techniques.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Tomoaki", "last_name": "Naka", "name": null }, { "creator_type": "author", "first_name": "Taiki", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Teruhiko", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null }, { "creator_type": "author", "first_name": "Shigeki", "last_name": "Sekine", "name": null } ], "identifiers": { "doi": { "normalized": "10.1097/pas.0000000000002012" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "36729478" } }, "mesh": [ { "descriptor": "Adenoma", "descriptor_ui": "D000236", "major_topic": true }, { "descriptor": "Adenomatous Polyps", "descriptor_ui": "D018256", "major_topic": false }, { "descriptor": "Gastric Mucosa", "descriptor_ui": "D005753", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": false }, { "descriptor": "Stomach", "descriptor_ui": "D013270", "major_topic": false }, { "descriptor": "Stomach Neoplasms", "descriptor_ui": "D013274", "major_topic": true } ], "publication": { "conference_name": null, "date": "2022 Dec 19", "date_precision": "day", "issue": "", "normalized_date": "2022-12-19", "pages": "", "proceedings_title": null, "publisher": "", "title": "The American journal of surgical pathology", "volume": "", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "KLF4 c.A1322C Mutation Is a Consistent and Specific Genetic Feature of Raspberry-like Foveolar-type Adenoma of the Stomach.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "OBJECTIVES: This study investigated the early progression patterns of lung squamous cell carcinoma (SqCC) on computed tomography (CT) images. MATERIALS AND METHODS: In total, 65 patients with SqCC who underwent surgical resection and two CT scans separated by an interval of at least 6 months were enrolled. We categorized the findings of the initial and at-diagnosis CT images into five patterns as previously reported. The volume doubling time (VDT) was calculated for measurable lesions. RESULTS: A single nodule pattern on CT images at-diagnosis was most common in 56 (86.2 %) patients, in line with practical clinical findings. However, the patterns were diverse in the initial images, with 28 (43.1 %) patients displaying atypical findings, including multiple nodules (3.1 %), endobronchial lesions (20.0 %), subsolid nodules (10.8 %), and cyst wall thickening (9.2 %). All endobronchial lesions were located in the central/middle zone of the lung field, whereas lesions presented as multiple nodules, subsolid nodules, and cyst wall thickening were predominantly observed in the peripheral zone. The differences in the developed zones were reflected in the median VDT, and the tumors with an initial endobronchial pattern had a significantly shorter VDT than those with a subsolid nodule pattern (median: 140 days vs 276 days, p < 0.001). CONCLUSIONS: Lung SqCC initiated with various CT image patterns, although most tumors ultimately developed a single nodule pattern by diagnosis. The initial CT image patterns differed between the hilar and peripheral zones, suggesting a difference in the progression scheme, which was also supported by differences in VDT.", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Haruto", "last_name": "Sugawara", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null }, { "creator_type": "author", "first_name": "Hirokazu", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Akai", "name": null }, { "creator_type": "author", "first_name": "Osamu", "last_name": "Abe", "name": null }, { "creator_type": "author", "first_name": "Shun-Ichi", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Masahiko", "last_name": "Kusumoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.lungcan.2022.12.007" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "36584605" } }, "mesh": [ { "descriptor": "Carcinoma, Non-Small-Cell Lung", "descriptor_ui": "D002289", "major_topic": true }, { "descriptor": "Carcinoma, Squamous Cell", "descriptor_ui": "D002294", "major_topic": true }, { "descriptor": "Cysts", "descriptor_ui": "D003560", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Lung", "descriptor_ui": "D008168", "major_topic": false }, { "descriptor": "Lung Neoplasms", "descriptor_ui": "D008175", "major_topic": true }, { "descriptor": "Retrospective Studies", "descriptor_ui": "D012189", "major_topic": false } ], "publication": { "conference_name": null, "date": "2022 Dec 19", "date_precision": "day", "issue": "", "normalized_date": "2022-12-19", "pages": "31-37", "proceedings_title": null, "publisher": "", "title": "Lung cancer (Amsterdam, Netherlands)", "volume": "176", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Radiological precursor lesions of lung squamous cell carcinoma: Early progression patterns and divergent volume doubling time between hilar and peripheral zones.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Epithelial cells remodel cell adhesion and change their neighbors to shape a tissue. This cellular rearrangement proceeds in three steps: the shrinkage of a junction, exchange of junctions, and elongation of the newly generated junction. Herein, by combining live imaging and physical modeling, we showed that the formation of myosin-II (myo-II) cables around the cell vertices underlies the exchange of junctions in the Drosophila wing epithelium. The local and transient detachment of myo-II from the cell cortex is regulated by the LIM domain-containing protein Jub and the tricellular septate junction protein M6. Moreover, we found that M6 shifts to the adherens junction plane on jub RNAi and that Jub is persistently retained at reconnecting junctions in m6 RNAi cells. This interplay between Jub and M6 can depend on the junction length and thereby couples the detachment of cortical myo-II cables and the shrinkage/elongation of the junction during cell rearrangement. Furthermore, we developed a mechanical model based on the wetting theory and clarified how the physical properties of myo-II cables are integrated with the junction geometry to induce the transition between the attached and detached states and support the unidirectionality of cell rearrangement. Collectively, this study elucidates the orchestration of geometry, mechanics, and signaling for exchanging junctions.", "classifications": [ { "id": "Ishihara", "label": "Group Ishihara", "parent": "Sawai", "type": "group" }, { "id": "Sawai", "label": "Team Sawai", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Keisuke", "last_name": "Ikawa", "name": null }, { "creator_type": "author", "first_name": "Shuji", "last_name": "Ishihara", "name": null }, { "creator_type": "author", "first_name": "Yoichiro", "last_name": "Tamori", "name": null }, { "creator_type": "author", "first_name": "Kaoru", "last_name": "Sugimura", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.cub.2022.11.067" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "36543168" } }, "mesh": [ { "descriptor": "Adherens Junctions", "descriptor_ui": "D022005", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Drosophila", "descriptor_ui": "D004330", "major_topic": true }, { "descriptor": "Drosophila melanogaster", "descriptor_ui": "D004331", "major_topic": false }, { "descriptor": "Drosophila Proteins", "descriptor_ui": "D029721", "major_topic": true }, { "descriptor": "Epithelium", "descriptor_ui": "D004848", "major_topic": false }, { "descriptor": "Intercellular Junctions", "descriptor_ui": "D007365", "major_topic": false }, { "descriptor": "Myosin Type II", "descriptor_ui": "D024462", "major_topic": false }, { "descriptor": "Myosins", "descriptor_ui": "D009218", "major_topic": false } ], "publication": { "conference_name": null, "date": "2022 Dec 15", "date_precision": "day", "issue": "", "normalized_date": "2022-12-15", "pages": "S0960-9822(22)01897-8", "proceedings_title": null, "publisher": "", "title": "Current biology : CB", "volume": "", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Attachment and detachment of cortical myosin regulates cell junction exchange during cell rearrangement in the Drosophila wing epithelium.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "", "classifications": [ { "id": "Enomoto", "label": "Group Enomoto", "parent": "Enomoto", "type": "group" }, { "id": "Enomoto", "label": "Team Enomoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Mukhamad", "last_name": "Sunardi", "name": null }, { "creator_type": "author", "first_name": "Keisuke", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Yuya", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Toshihiro", "last_name": "Uesaka", "name": null }, { "creator_type": "author", "first_name": "Mitsuhiro", "last_name": "Iwasaki", "name": null }, { "creator_type": "author", "first_name": "Hideki", "last_name": "Enomoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.jcmgh.2022.12.003" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "36521661" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Enteric Nervous System", "descriptor_ui": "D017615", "major_topic": true }, { "descriptor": "Hirschsprung Disease", "descriptor_ui": "D006627", "major_topic": true }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Proto-Oncogene Proteins c-ret", "descriptor_ui": "D051096", "major_topic": false } ], "publication": { "conference_name": null, "date": "2022-12-12", "date_precision": "day", "issue": "0", "normalized_date": "2022-12-12", "pages": "", "proceedings_title": null, "publisher": "Elsevier", "title": "Cellular and Molecular Gastroenterology and Hepatology", "volume": "0", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "A Single RET Mutation in Hirschsprung Disease Induces Intestinal Aganglionosis Via a Dominant-Negative Mechanism", "url": "https://www.cmghjournal.org/article/S2352-345X(22)00251-X/fulltext", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: Since the 8(th) edition of UICC/AJCC TNM classification system the primary tumor pT stage is determined based on presence and size of the invasive components. The aim of this study was to identify histological features in tumors with lepidic growth pattern that may be used to establish criteria for distinguishing invasive from non-invasive areas. MATERIALS AND METHODS: A Delphi approach was used with two rounds of blinded anonymized analysis of resected non-mucinous lung adenocarcinoma cases with presumed invasive and non-invasive components, followed by one round of reviewer de-anonymized and unblinded review of cases with known outcomes. A digital pathology platform was used for measuring total tumor size and invasive tumor size. RESULTS: The mean coefficient of variation for measuring total tumor size and tumor invasive size was 6.9% (range 1.7-22.3%) and 54% (range 14.7-155%), respectively, with substantial variations in interpretation of the size and location of invasion among pathologists. Following the presentation of the results and further discussion among members at large of the IASLC Pathology Committee, extensive epithelial proliferation (EEP) in areas of collapsed lepidic growth pattern is recognized as a feature likely to be associated with invasive growth. EEP is characterized by multilayered luminal epithelial cell growth, usually with high grade cytological features in several alveolar spaces. CONCLUSION: Collapsed alveoli and transition zones with EEP were identified by the Delphi process as morphologic features that were a source of interobserver variability. Definition criteria for collapse and EEP are proposed to improve reproducibility of invasion measurement.", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Erik", "last_name": "Thunnissen", "name": null }, { "creator_type": "author", "first_name": "Mary Beth", "last_name": "Beasley", "name": null }, { "creator_type": "author", "first_name": "Alain", "last_name": "Borczuk", "name": null }, { "creator_type": "author", "first_name": "Sanja", "last_name": "Dacic", "name": null }, { "creator_type": "author", "first_name": "Keith M.", "last_name": "Kerr", "name": null }, { "creator_type": "author", "first_name": "Yuko", "last_name": "Minami", "name": null }, { "creator_type": "author", "first_name": "Andrew G.", "last_name": "Nicholson", "name": null }, { "creator_type": "author", "first_name": "Lynette", "last_name": "Sholl", "name": null }, { "creator_type": "author", "first_name": "Ming-Sound", "last_name": "Tsao", "name": null }, { "creator_type": "author", "first_name": "Masayuki", "last_name": "Noguchi", "name": null }, { "creator_type": "author", "first_name": "Birgit", "last_name": "Lissenberg-Witte", "name": null }, { "creator_type": "author", "first_name": "John", "last_name": "Le Quesne", "name": null }, { "creator_type": "author", "first_name": "Anja C.", "last_name": "Roden", "name": null }, { "creator_type": "author", "first_name": "Jin-Haeng", "last_name": "Chung", "name": null }, { "creator_type": "author", "first_name": "Akihiko", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Andre L.", "last_name": "Moreira", "name": null }, { "creator_type": "author", "first_name": "Sylvie", "last_name": "Lantuejoul", "name": null }, { "creator_type": "author", "first_name": "Giuseppe", "last_name": "Pelosi", "name": null }, { "creator_type": "author", "first_name": "Claudia", "last_name": "Poleri", "name": null }, { "creator_type": "author", "first_name": "David", "last_name": "Hwang", "name": null }, { "creator_type": "author", "first_name": "Deepali", "last_name": "Jain", "name": null }, { "creator_type": "author", "first_name": "William D.", "last_name": "Travis", "name": null }, { "creator_type": "author", "first_name": "Elisabeth", "last_name": "Brambilla", "name": null }, { "creator_type": "author", "first_name": "Gang", "last_name": "Chen", "name": null }, { "creator_type": "author", "first_name": "Johan", "last_name": "Botling", "name": null }, { "creator_type": "author", "first_name": "Lukas", "last_name": "Bubendorf", "name": null }, { "creator_type": "author", "first_name": "Mari", "last_name": "Mino-Kenudson", "name": null }, { "creator_type": "author", "first_name": "Noriko", "last_name": "Motoi", "name": null }, { "creator_type": "author", "first_name": "Teh Ying", "last_name": "Chou", "name": null }, { "creator_type": "author", "first_name": "Mauro", "last_name": "Papotti", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null }, { "creator_type": "author", "first_name": "Wendy", "last_name": "Cooper", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.jtho.2022.11.026" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "36503176" } }, "mesh": [ { "descriptor": "Adenocarcinoma", "descriptor_ui": "D000230", "major_topic": true }, { "descriptor": "Adenocarcinoma of Lung", "descriptor_ui": "D000077192", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Lung Neoplasms", "descriptor_ui": "D008175", "major_topic": true }, { "descriptor": "Neoplasm Invasiveness", "descriptor_ui": "D009361", "major_topic": false }, { "descriptor": "Neoplasm Staging", "descriptor_ui": "D009367", "major_topic": false }, { "descriptor": "Reproducibility of Results", "descriptor_ui": "D015203", "major_topic": false } ], "publication": { "conference_name": null, "date": "2022 Dec 8", "date_precision": "day", "issue": "", "normalized_date": "2022-12-08", "pages": "S1556-0864(22)01936-0", "proceedings_title": null, "publisher": "", "title": "Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer", "volume": "", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Defining morphologic features of invasion in pulmonary non-mucinous adenocarcinoma with lepidic growth - A proposal by the IASLC Pathology Committee.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Masaya", "last_name": "Yotsukura", "name": null }, { "creator_type": "author", "first_name": "Yuji", "last_name": "Muraoka", "name": null }, { "creator_type": "author", "first_name": "Yukihiro", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Kazuo", "last_name": "Nakagawa", "name": null }, { "creator_type": "author", "first_name": "Kouya", "last_name": "Shiraishi", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Kohno", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null }, { "creator_type": "author", "first_name": "Shun-Ichi", "last_name": "Watanabe", "name": null } ], "identifiers": { "doi": { "normalized": "10.1245/s10434-022-12718-3" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "36472783" } }, "mesh": [], "publication": { "conference_name": null, "date": "2022 Dec 6", "date_precision": "day", "issue": "", "normalized_date": "2022-12-06", "pages": "", "proceedings_title": null, "publisher": "", "title": "Annals of surgical oncology", "volume": "", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "ASO Visual Abstract: Long-Term Prognosis and Prognostic Indicators of Stage IA Lung Adenocarcinoma.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Necroptosis is a regulated form of cell death involved in various pathological conditions, including ischemic reperfusion injuries, virus infections, and drug-induced tissue injuries. However, it is not fully understood when and where necroptosis occurs in vivo. We previously generated a Forster resonance energy transfer (FRET) biosensor, termed SMART (the sensor for MLKL activation by RIPK3 based on FRET), which monitors conformational changes of MLKL along with progression of necroptosis in human and murine cell lines in vitro. Here, we generate transgenic (Tg) mice that express the SMART biosensor in various tissues. The FRET ratio is increased in necroptosis, but not apoptosis or pyroptosis, in primary cells. Moreover, the FRET signals are elevated in renal tubular cells of cisplatin-treated SMART Tg mice compared to untreated SMART Tg mice. Together, SMART Tg mice may provide a valuable tool for monitoring necroptosis in different types of cells in vitro and in vivo.", "classifications": [], "creators": [ { "creator_type": "author", "first_name": "Shin", "last_name": "Murai", "name": null }, { "creator_type": "author", "first_name": "Kanako", "last_name": "Takakura", "name": null }, { "creator_type": "author", "first_name": "Kenta", "last_name": "Sumiyama", "name": null }, { "creator_type": "author", "first_name": "Kenta", "last_name": "Moriwaki", "name": null }, { "creator_type": "author", "first_name": "Kenta", "last_name": "Terai", "name": null }, { "creator_type": "author", "first_name": "Sachiko", "last_name": "Komazawa-Sakon", "name": null }, { "creator_type": "author", "first_name": "Takao", "last_name": "Seki", "name": null }, { "creator_type": "author", "first_name": "Yoshifumi", "last_name": "Yamaguchi", "name": null }, { "creator_type": "author", "first_name": "Tetuo", "last_name": "Mikami", "name": null }, { "creator_type": "author", "first_name": "Kimi", "last_name": "Araki", "name": null }, { "creator_type": "author", "first_name": "Masaki", "last_name": "Ohmuraya", "name": null }, { "creator_type": "author", "first_name": "Michiyuki", "last_name": "Matsuda", "name": null }, { "creator_type": "author", "first_name": "Hiroyasu", "last_name": "Nakano", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s42003-022-04300-0" }, "pmcid": { "normalized": "PMC9722793" }, "pmid": { "normalized": "36471162" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Biosensing Techniques", "descriptor_ui": "D015374", "major_topic": true }, { "descriptor": "Fluorescence Resonance Energy Transfer", "descriptor_ui": "D031541", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Transgenic", "descriptor_ui": "D008822", "major_topic": false }, { "descriptor": "Necroptosis", "descriptor_ui": "D000079302", "major_topic": true }, { "descriptor": "Protein Kinases", "descriptor_ui": "D011494", "major_topic": false } ], "publication": { "conference_name": null, "date": "2022 Dec 5", "date_precision": "day", "issue": "1", "normalized_date": "2022-12-05", "pages": "1331", "proceedings_title": null, "publisher": "", "title": "Communications biology", "volume": "5", "year": 2022 }, "ssbd": { "database": [ "ssbd-database-000276" ], "repository": [ "ssbd-repos-000276" ] }, "title": "Generation of transgenic mice expressing a FRET biosensor, SMART, that responds to necroptosis.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Follicular neoplasms of the thyroid include follicular thyroid carcinoma (FTC) and follicular thyroid adenoma (FTA). However, the differences in cytological findings between FTC and FTA remain undetermined. Here, we aimed to evaluate the accumulation of lipid droplets (LDs) and the expression of adipophilin (perilipin 2/ADRP/ADFP), a known LD marker, in cultured FTC cells. We also immunohistochemically compared adipophilin expression in the FTC and FTA of resected human thyroid tissues. Cultured FTC (FTC-133 and RO82W-1) possessed increased populations of LDs compared to thyroid follicular epithelial (Nthy-ori 3-1) cells. In vitro treatment with phosphatidylinositol-3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) signaling inhibitors (LY294002, MK2206, and rapamycin) in FTC-133 cells downregulated the PI3K/Akt/mTOR/sterol regulatory element-binding protein 1 (SREBP1) signaling pathway, resulting in a significant reduction in LD accumulation. SREBP1 is a master transcription factor that controls lipid metabolism. Fluorescence immunocytochemistry revealed adipophilin expression in the LDs of FTC-133 cells. Immunohistochemical analysis of surgically resected human thyroid tissues revealed significantly increased expression of adipophilin in FTC compared with FTA and adjacent non-tumorous thyroid epithelia. Taken together, LDs and adipophilin were abundant in cultured FTC; the evaluation of adipophilin expression can help distinguish FTC from FTA in surgical specimens.", "classifications": [ { "id": "Fujita", "label": "Group Fujita", "parent": "Fujita", "type": "group" }, { "id": "Tanaka", "label": "Group Tanaka", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Michiyo", "last_name": "Hayakawa", "name": null }, { "creator_type": "author", "first_name": "J. Nicholas", "last_name": "Taylor", "name": null }, { "creator_type": "author", "first_name": "Ryuta", "last_name": "Nakao", "name": null }, { "creator_type": "author", "first_name": "Kentaro", "last_name": "Mochizuki", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Sawai", "name": null }, { "creator_type": "author", "first_name": "Kosuke", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Tabata", "name": null }, { "creator_type": "author", "first_name": "Yasuaki", "last_name": "Kumamoto", "name": null }, { "creator_type": "author", "first_name": "Katsumasa", "last_name": "Fujita", "name": null }, { "creator_type": "author", "first_name": "Eiichi", "last_name": "Konishi", "name": null }, { "creator_type": "author", "first_name": "Shigeru", "last_name": "Hirano", "name": null }, { "creator_type": "author", "first_name": "Hideo", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Tamiki", "last_name": "Komatsuzaki", "name": null }, { "creator_type": "author", "first_name": "Yoshinori", "last_name": "Harada", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.bbrc.2022.12.007" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "36521425" } }, "mesh": [ { "descriptor": "Adenocarcinoma, Follicular", "descriptor_ui": "D018263", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Lipid Droplets", "descriptor_ui": "D066292", "major_topic": false }, { "descriptor": "Perilipin-2", "descriptor_ui": "D000070780", "major_topic": false }, { "descriptor": "Phosphatidylinositol 3-Kinase", "descriptor_ui": "D058539", "major_topic": false }, { "descriptor": "Phosphatidylinositol 3-Kinases", "descriptor_ui": "D019869", "major_topic": false }, { "descriptor": "Proto-Oncogene Proteins c-akt", "descriptor_ui": "D051057", "major_topic": false }, { "descriptor": "Thyroid Neoplasms", "descriptor_ui": "D013964", "major_topic": true }, { "descriptor": "TOR Serine-Threonine Kinases", "descriptor_ui": "D058570", "major_topic": false } ], "publication": { "conference_name": null, "date": "2022 Dec 5", "date_precision": "day", "issue": "", "normalized_date": "2022-12-05", "pages": "192-201", "proceedings_title": null, "publisher": "", "title": "Biochemical and biophysical research communications", "volume": "640", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Lipid droplet accumulation and adipophilin expression in follicular thyroid carcinoma.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Ovarian clear cell carcinoma (OCCC) has a poor prognosis, and its therapeutic strategy has not been established. PRELP is a leucine-rich repeat protein in the extracellular matrix of connective tissues. Although PRELP anchors the basement membrane to the connective tissue and is absent in most epithelial cancers, much remains unknown regarding its function as a regulator of ligand-mediated signaling pathways. Here, we obtained sets of differentially expressed genes by PRELP expression using OCCC cell lines. We found that more than 1000 genes were significantly altered by PRELP expression, particularly affecting the expression of a group of genes involved in the PI3K-AKT signaling pathway. Furthermore, we revealed the loss of active histone marks on the loci of the PRELP gene in patients with OCCC and how its forced expression inhibited cell proliferation. These findings suggest that PRELP is not only a molecule anchored in connective tissues but is also a signaling molecule acting in a tumor-suppressive manner. It can serve as the basis for early detection and novel therapeutic approaches for OCCC toward precision medicine.", "classifications": [ { "id": "Hamamoto", "label": "Group Hamamoto", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Ai", "last_name": "Dozen", "name": null }, { "creator_type": "author", "first_name": "Kanto", "last_name": "Shozu", "name": null }, { "creator_type": "author", "first_name": "Norio", "last_name": "Shinkai", "name": null }, { "creator_type": "author", "first_name": "Noriko", "last_name": "Ikawa", "name": null }, { "creator_type": "author", "first_name": "Rina", "last_name": "Aoyama", "name": null }, { "creator_type": "author", "first_name": "Hidenori", "last_name": "Machino", "name": null }, { "creator_type": "author", "first_name": "Ken", "last_name": "Asada", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Tomoyasu", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Ryuji", "last_name": "Hamamoto", "name": null }, { "creator_type": "author", "first_name": "Syuzo", "last_name": "Kaneko", "name": null }, { "creator_type": "author", "first_name": "Masaaki", "last_name": "Komatsu", "name": null } ], "identifiers": { "doi": { "normalized": "10.3390/jpm12121999" }, "pmcid": { "normalized": "PMC9785654" }, "pmid": { "normalized": "36556220" } }, "mesh": [], "publication": { "conference_name": null, "date": "2022 Dec 2", "date_precision": "day", "issue": "12", "normalized_date": "2022-12-02", "pages": "", "proceedings_title": null, "publisher": "", "title": "Journal of personalized medicine", "volume": "12", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Tumor Suppressive Role of the PRELP Gene in Ovarian Clear Cell Carcinoma.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "SUMMARY: In this study, we herein describe a 47-year-old Japanese woman who manifested inheritable non-alcoholic steatohepatitis (NASH) and severe dyslipidemia. Interestingly, her NASH progression was ameliorated by treatment with a sodium-glucose co-transporter 2 (SGLT2) inhibitor. This inheritability prompted us to comprehensively decode her genomic information using whole-exome sequencing. We found the well-established I148M mutation in PNPLA3 as well as mutations in LGALS3 and PEMT for her NASH. Mutations in GCKR may contribute to both NASH and dyslipidemia. We further mined gene mutations potentially responsible for her manifestations that led to the identification of a novel M188fs mutation in MUL1 that may be causally associated with her mitochondrial dysfunction. Our case may provide some clues to better understand this spectrum of disease as well as the rationale for selecting medications. LEARNING POINTS: While the PNPLA3 I148M mutation is well-established, accumulation of other mutations may accelerate susceptibility to non-alcoholic steatohepatitis (NASH). NASH and dyslipidemia may be intertwined biochemically and genetically through several key genes. SGLT2 inhibitors emerge as promising treatment for NASH albeit with interindividual variation in efficacy. Genetic background may explain the mechanisms behind the variation. A novel dysfunctional mutation in MUL1 may lead to metabolic inflexibilities through impaired mitochondrial dynamics and function.", "classifications": [ { "id": "Miyamoto", "label": "Group Miyamoto", "parent": "Wakamoto", "type": "group" }, { "id": "Wakamoto", "label": "Team Wakamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Rikako", "last_name": "Nakajima", "name": null }, { "creator_type": "author", "first_name": "Motohiro", "last_name": "Sekiya", "name": null }, { "creator_type": "author", "first_name": "Yasuhisa", "last_name": "Furuta", "name": null }, { "creator_type": "author", "first_name": "Takafumi", "last_name": "Miyamoto", "name": null }, { "creator_type": "author", "first_name": "Masashi", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Kuniaki", "last_name": "Fukuda", "name": null }, { "creator_type": "author", "first_name": "Keiichiro", "last_name": "Hattori", "name": null }, { "creator_type": "author", "first_name": "Yasuhito", "last_name": "Suehara", "name": null }, { "creator_type": "author", "first_name": "Mamiko", "last_name": "Sakata-Yanagimoto", "name": null }, { "creator_type": "author", "first_name": "Shigeru", "last_name": "Chiba", "name": null }, { "creator_type": "author", "first_name": "Yuka", "last_name": "Okajima", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Matsuzaka", "name": null }, { "creator_type": "author", "first_name": "Satoru", "last_name": "Takase", "name": null }, { "creator_type": "author", "first_name": "Mikio", "last_name": "Takanashi", "name": null }, { "creator_type": "author", "first_name": "Hiroaki", "last_name": "Okazaki", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Takashima", "name": null }, { "creator_type": "author", "first_name": "Mikiko", "last_name": "Yuhara", "name": null }, { "creator_type": "author", "first_name": "Yuta", "last_name": "Mitani", "name": null }, { "creator_type": "author", "first_name": "Nako", "last_name": "Matsumoto", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Murayama", "name": null }, { "creator_type": "author", "first_name": "Mariko", "last_name": "Ohyama Osawa", "name": null }, { "creator_type": "author", "first_name": "Nami", "last_name": "Ohuchi", "name": null }, { "creator_type": "author", "first_name": "Daichi", "last_name": "Yamazaki", "name": null }, { "creator_type": "author", "first_name": "Sayuri", "last_name": "Mori", "name": null }, { "creator_type": "author", "first_name": "Yoko", "last_name": "Sugano", "name": null }, { "creator_type": "author", "first_name": "Yoshinori", "last_name": "Osaki", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Iwasaki", "name": null }, { "creator_type": "author", "first_name": "Hiroaki", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Shimano", "name": null } ], "identifiers": { "doi": { "normalized": "10.1530/edm-22-0368" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "36571472" } }, "mesh": [], "publication": { "conference_name": null, "date": "2022 Dec 1", "date_precision": "day", "issue": "", "normalized_date": "2022-12-01", "pages": "22-0368", "proceedings_title": null, "publisher": "", "title": "Endocrinology, diabetes & metabolism case reports", "volume": "2022", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "A case of NASH with genetic predisposition successfully treated with an SGLT2 inhibitor: a possible involvement of mitochondrial dysfunction.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Myocardial damage caused by the newly emerged coronavirus (SARS-CoV-2) infection is one of the key determinants of COVID-19 severity and mortality. SARS-CoV-2 entry to host cells is initiated by binding with its receptor, angiotensin-converting enzyme (ACE) 2, and the ACE2 abundance is thought to reflect the susceptibility to infection. Here, we report that ibudilast, which we previously identified as a potent inhibitor of protein complex between transient receptor potential canonical (TRPC) 3 and NADPH oxidase (Nox) 2, attenuates the SARS-CoV-2 spike glycoprotein pseudovirus-evoked contractile and metabolic dysfunctions of neonatal rat cardiomyocytes (NRCMs). Epidemiologically reported risk factors of severe COVID-19, including cigarette sidestream smoke (CSS) and anti-cancer drug treatment, commonly upregulate ACE2 expression level, and these were suppressed by inhibiting TRPC3-Nox2 complex formation. Exposure of NRCMs to SARS-CoV-2 pseudovirus, as well as CSS and doxorubicin (Dox), induces ATP release through pannexin-1 hemi-channels, and this ATP release potentiates pseudovirus entry to NRCMs and human iPS cell-derived cardiomyocytes (hiPS-CMs). As the pseudovirus entry followed by production of reactive oxygen species was attenuated by inhibiting TRPC3-Nox2 complex in hiPS-CMs, we suggest that TRPC3-Nox2 complex formation triggered by panexin1-mediated ATP release participates in exacerbation of myocardial damage by amplifying ACE2-dependent SARS-CoV-2 entry.", "classifications": [ { "id": "JPMJCR2024", "label": "JPMJCR2024", "researcher": "Motohiro Nishida", "type": "grant" }, { "id": "Nishida", "label": "Group Nishida", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yuri", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Kazuhiro", "last_name": "Nishiyama", "name": null }, { "creator_type": "author", "first_name": "Jae", "last_name": "Man Lee", "name": null }, { "creator_type": "author", "first_name": "Yuko", "last_name": "Ibuki", "name": null }, { "creator_type": "author", "first_name": "Yumiko", "last_name": "Imai", "name": null }, { "creator_type": "author", "first_name": "Takamasa", "last_name": "Noda", "name": null }, { "creator_type": "author", "first_name": "Noriho", "last_name": "Kamiya", "name": null }, { "creator_type": "author", "first_name": "Takahiro", "last_name": "Kusakabe", "name": null }, { "creator_type": "author", "first_name": "Yasunari", "last_name": "Kanda", "name": null }, { "creator_type": "author", "first_name": "Motohiro", "last_name": "Nishida", "name": null } ], "identifiers": { "doi": { "normalized": "10.3390/ijms24010102" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "36613540" } }, "mesh": [ { "descriptor": "Adenosine Triphosphate", "descriptor_ui": "D000255", "major_topic": false }, { "descriptor": "Angiotensin-Converting Enzyme 2", "descriptor_ui": "D000085962", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "COVID-19", "descriptor_ui": "D000086382", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Myocytes, Cardiac", "descriptor_ui": "D032383", "major_topic": false }, { "descriptor": "NADPH Oxidase 2", "descriptor_ui": "D000074662", "major_topic": true }, { "descriptor": "Protein Binding", "descriptor_ui": "D011485", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "SARS-CoV-2", "descriptor_ui": "D000086402", "major_topic": false }, { "descriptor": "Spike Glycoprotein, Coronavirus", "descriptor_ui": "D064370", "major_topic": false }, { "descriptor": "TRPC Cation Channels", "descriptor_ui": "D050052", "major_topic": true }, { "descriptor": "Up-Regulation", "descriptor_ui": "D015854", "major_topic": false } ], "publication": { "conference_name": null, "date": "2022-12", "date_precision": "month", "issue": "1", "normalized_date": "2022-12", "pages": "102", "proceedings_title": null, "publisher": "", "title": "International Journal of Molecular Sciences", "volume": "24", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "TRPC3-Nox2 Protein Complex Formation Increases the Risk of SARS-CoV-2 Spike Protein-Induced Cardiomyocyte Dysfunction through ACE2 Upregulation", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "DNA topoisomerase II (TOP2) is an enzyme that resolves DNA topological problems and plays critical roles in various nuclear processes. Recently, a heterozygous H58Y substitution in the ATPase domain of human TOP2B was identified from patients with autism spectrum disorder, but its biological significance remains unclear. In this study, we analyzed the nuclear dynamics of TOP2B with H58Y (TOP2B H58Y). Although wild-type TOP2B was highly mobile in the nucleus of a living cell, the nuclear mobility of TOP2B H58Y was markedly reduced, suggesting that the impact of H58Y manifests as low protein mobility. We found that TOP2B H58Y is insensitive to ICRF-187, a TOP2 inhibitor that halts TOP2 as a closed clamp on DNA. When the ATPase activity of TOP2B was compromised, the nuclear mobility of TOP2B H58Y was restored to wild-type levels, indicating the contribution of the ATPase activity to the low nuclear mobility. Analysis of genome-edited cells harboring TOP2B H58Y showed that TOP2B H58Y retains sensitivity to the TOP2 poison etoposide, implying that TOP2B H58Y can undergo at least a part of its catalytic reactions. Collectively, TOP2 H58Y represents a unique example of the relationship between a disease-associated mutation and perturbed protein dynamics.", "classifications": [ { "id": "Higaki", "label": "Group Higaki", "parent": "Ueda", "type": "group" }, { "id": "Ueda", "label": "Team Ueda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Keiko", "last_name": "Morotomi-Yano", "name": null }, { "creator_type": "author", "first_name": "Yukiko", "last_name": "Hiromoto", "name": null }, { "creator_type": "author", "first_name": "Takumi", "last_name": "Higaki", "name": null }, { "creator_type": "author", "first_name": "Ken-Ichi", "last_name": "Yano", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41598-022-24883-2" }, "pmcid": { "normalized": "PMC9712534" }, "pmid": { "normalized": "36450898" } }, "mesh": [ { "descriptor": "Adenosine Triphosphatases", "descriptor_ui": "D000251", "major_topic": false }, { "descriptor": "Autism Spectrum Disorder", "descriptor_ui": "D000067877", "major_topic": true }, { "descriptor": "Cell Nucleus", "descriptor_ui": "D002467", "major_topic": false }, { "descriptor": "DNA Topoisomerases, Type II", "descriptor_ui": "D004250", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": false } ], "publication": { "conference_name": null, "date": "2022 Nov 30", "date_precision": "day", "issue": "1", "normalized_date": "2022-11-30", "pages": "20627", "proceedings_title": null, "publisher": "", "title": "Scientific reports", "volume": "12", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Disease-associated H58Y mutation affects the nuclear dynamics of human DNA topoisomerase IIbeta.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Histone methyltransferase SETD1A is critical for acute myeloid leukemia (AML) cell survival, but the molecular mechanism driving SETD1A gene regulation remains elusive. To delineate the role of SETD1A, we utilize a protein degrader technology to induce rapid SETD1A degradation in AML cell lines. SETD1A degradation results in immediate downregulation of transcripts associated with DNA repair and heme biosynthesis pathways. CRISPR-based functional analyses and metabolomics reveal an essential role of SETD1A to maintain mitochondrial respiration in AML cells. These SETD1A targets are enriched in head-to-head (H2H) genes. SETD1A degradation disrupts a non-enzymatic SETD1A domain-dependent cyclin K function, increases the Ser5P RNA polymerase II (RNAPII) at the transcriptional start site (TSS), and induces the promoter-proximal pausing of RNAPII in a strand-specific manner. This study reveals a non-enzymatic role for SETD1A in transcriptional pause release and provides insight into the mechanism of RNAPII pausing and its function in cancer.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Takayuki", "last_name": "Hoshii", "name": null }, { "creator_type": "author", "first_name": "Sarah", "last_name": "Perlee", "name": null }, { "creator_type": "author", "first_name": "Sota", "last_name": "Kikuchi", "name": null }, { "creator_type": "author", "first_name": "Bahityar", "last_name": "Rahmutulla", "name": null }, { "creator_type": "author", "first_name": "Masaki", "last_name": "Fukuyo", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Masuda", "name": null }, { "creator_type": "author", "first_name": "Sumio", "last_name": "Ohtsuki", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Behnam", "last_name": "Nabet", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Kaneda", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.celrep.2022.111727" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "36450243" } }, "mesh": [ { "descriptor": "DNA Repair", "descriptor_ui": "D004260", "major_topic": false }, { "descriptor": "Down-Regulation", "descriptor_ui": "D015536", "major_topic": false }, { "descriptor": "Heme", "descriptor_ui": "D006418", "major_topic": false }, { "descriptor": "Histone-Lysine N-Methyltransferase", "descriptor_ui": "D011495", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Leukemia", "descriptor_ui": "D007938", "major_topic": true }, { "descriptor": "Metabolomics", "descriptor_ui": "D055432", "major_topic": false }, { "descriptor": "RNA Polymerase II", "descriptor_ui": "D012319", "major_topic": false } ], "publication": { "conference_name": null, "date": "2022 Nov 29", "date_precision": "day", "issue": "9", "normalized_date": "2022-11-29", "pages": "111727", "proceedings_title": null, "publisher": "", "title": "Cell reports", "volume": "41", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "SETD1A regulates transcriptional pause release of heme biosynthesis genes in leukemia.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Efficient delivery of subunit vaccines to dendritic cells (DCs) is necessary to improve vaccine efficacy, because the vaccine antigen alone cannot induce sufficient protective immunity. Here, we identified DC-targeting peptides using a phage display system and demonstrated the potential of these peptides as antigen-delivery carriers to improve subunit vaccine effectiveness in mice. The fusion of antigen proteins and peptides with DC-targeting peptides induced strong antigen-specific IgG responses, even in the absence of adjuvants. In addition, the DC-targeting peptide improved the distribution of antigens to DCs and antigen presentation by DCs. The combined use of an adjuvant with a DC-targeting peptide improved the effectiveness of the vaccine. Furthermore, nucleolin, located on the DC surface, was identified as the receptor for DC-targeting peptide, and nucleolin was indispensable for the vaccine effect of the DC-targeting peptide. Overall, the findings of this study could be useful for developing subunit vaccines against infectious diseases.", "classifications": [ { "id": "Yamamoto", "label": "Group Yamamoto", "parent": "Toyoshima", "type": "group" }, { "id": "Toyoshima", "label": "Team Toyoshima", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Teppei", "last_name": "Matsuda", "name": null }, { "creator_type": "author", "first_name": "Kazuki", "last_name": "Misato", "name": null }, { "creator_type": "author", "first_name": "Shigeyuki", "last_name": "Tamiya", "name": null }, { "creator_type": "author", "first_name": "Yasuhiro", "last_name": "Akeda", "name": null }, { "creator_type": "author", "first_name": "Ikuhiko", "last_name": "Nakase", "name": null }, { "creator_type": "author", "first_name": "Etsushi", "last_name": "Kuroda", "name": null }, { "creator_type": "author", "first_name": "Shokichi", "last_name": "Takahama", "name": null }, { "creator_type": "author", "first_name": "Motohiro", "last_name": "Nonaka", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Michiko N.", "last_name": "Fukuda", "name": null }, { "creator_type": "author", "first_name": "Yasuo", "last_name": "Yoshioka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.isci.2022.105324" }, "pmcid": { "normalized": "PMC9593262" }, "pmid": { "normalized": "36304121" } }, "mesh": [], "publication": { "conference_name": null, "date": "2022 Nov 18", "date_precision": "day", "issue": "11", "normalized_date": "2022-11-18", "pages": "105324", "proceedings_title": null, "publisher": "", "title": "iScience", "volume": "25", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Efficient antigen delivery by dendritic cell-targeting peptide via nucleolin confers superior vaccine effects in mice.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Suvorexant (Belsomra(R)), a dual orexin receptor antagonist widely used in the treatment of insomnia, inhibits the arousal system in the brain. However, the drug's ventilatory effects have not been fully explored. This study aims to investigate the expression of orexin receptors in respiratory neurons and the effects of suvorexant on ventilation. Immunohistology of brainstem orexin receptor OX2R expression was performed in adult mice (n = 4) in (1) rostral ventral respiratory group (rVRG) neurons projecting to the phrenic nucleus (PhN) retrogradely labeled by Fluoro-Gold (FG) tracer, (2) neurons immunoreactive for paired like homeobox 2b (Phox2b) in the parafacial respiratory group/retrotrapezoid nucleus (pFRG/RTN), and (3) neurons immunoreactive for neurokinin 1 receptor (NK1R) and somatostatin (SST) in the preBotzinger complex (preBotC). Additionally, we measured in vivo ventilatory responses to hyperoxic hypercapnia (5% CO2) and hypoxia (10% O2) before and after suvorexant pretreatment (10 and cumulative 100 mg/kg) in unrestrained mice (n = 10) in a body plethysmograph. We found the OX2R immunoreactive materials in pFRG/RTN Phox2b and preBotC NK1R/SST immunoreactive neurons but not in FG-labeled rVRG neurons, which suggests the involvement of orexin in respiratory control. Further, suvorexant expressly suppressed the hypercapnic ventilatory augmentation, otherwise unaffecting ventilation. Central orexin is involved in shaping the hypercapnic ventilatory chemosensitivity. Suppression of hypercapnic ventilatory augmentation by the orexin receptor antagonist suvorexant calls for caution in its use in pathologies that may progress to hypercapnic respiratory failure, or sleep-disordered breathing. Clinical trials are required to explore the role of targeted pharmacological inhibition of orexin in ventilatory pathologies.", "classifications": [ { "id": "Yokota", "label": "Group Yokota", "parent": "Enomoto", "type": "group" }, { "id": "Enomoto", "label": "Team Enomoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Isato", "last_name": "Fukushi", "name": null }, { "creator_type": "author", "first_name": "Shigefumi", "last_name": "Yokota", "name": null }, { "creator_type": "author", "first_name": "Kotaro", "last_name": "Takeda", "name": null }, { "creator_type": "author", "first_name": "Jiro", "last_name": "Terada", "name": null }, { "creator_type": "author", "first_name": "Akira", "last_name": "Umeda", "name": null }, { "creator_type": "author", "first_name": "Masashi", "last_name": "Yoshizawa", "name": null }, { "creator_type": "author", "first_name": "Yosuke", "last_name": "Kono", "name": null }, { "creator_type": "author", "first_name": "Yohei", "last_name": "Hasebe", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Onimaru", "name": null }, { "creator_type": "author", "first_name": "Mieczyslaw", "last_name": "Pokorski", "name": null }, { "creator_type": "author", "first_name": "Yasumasa", "last_name": "Okada", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.brainres.2022.148061" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "36037880" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Azepines", "descriptor_ui": "D001381", "major_topic": false }, { "descriptor": "Carbon Dioxide", "descriptor_ui": "D002245", "major_topic": false }, { "descriptor": "Hypercapnia", "descriptor_ui": "D006935", "major_topic": true }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Orexin Receptor Antagonists", "descriptor_ui": "D000068796", "major_topic": true }, { "descriptor": "Orexin Receptors", "descriptor_ui": "D064446", "major_topic": false }, { "descriptor": "Orexins", "descriptor_ui": "D000068797", "major_topic": false }, { "descriptor": "Receptors, Neurokinin-1", "descriptor_ui": "D018040", "major_topic": false }, { "descriptor": "Somatostatin", "descriptor_ui": "D013004", "major_topic": false }, { "descriptor": "Transcription Factors", "descriptor_ui": "D014157", "major_topic": false }, { "descriptor": "Triazoles", "descriptor_ui": "D014230", "major_topic": false } ], "publication": { "conference_name": null, "date": "2022 Nov 15", "date_precision": "day", "issue": "", "normalized_date": "2022-11-15", "pages": "148061", "proceedings_title": null, "publisher": "", "title": "Brain research", "volume": "1795", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Dual orexin receptor blocker suvorexant attenuates hypercapnic ventilatory augmentation in mice.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Recent advances in RNA studies have revealed that functional long noncoding RNAs (lncRNAs) contribute to the biology of cancers. In breast cancer, estrogen receptor α (ERα) is an essential transcription factor that primarily promotes the growth of luminal-type cancer, although only a small number of lncRNAs are identified as direct ERα targets and modulators for ERα signaling. In this study, we performed RNA-sequencing for ER-positive breast cancer cells and identified a novel estrogen-inducible antisense RNA in the COL18A1 promoter region, named breast cancer natural antisense transcript 1 (BNAT1). In clinicopathological study, BNAT1 may have clinical relevance as a potential diagnostic factor for prognoses of ER-positive breast cancer patients based on an in situ hybridization study for breast cancer specimens. siRNA-mediated BNAT1 silencing significantly inhibited the in vitro and in vivo growth of tamoxifen-resistant ER-positive breast cancer cells. Notably, BNAT1 silencing repressed cell cycle progression whereas it promoted apoptosis. Microarray analysis revealed that BNAT1 silencing in estrogen-sensitive breast cancer cells repressed estrogen signaling. We showed that BNAT1 knockdown decreased ERα expression and repressed ERα transactivation. RNA immunoprecipitation showed that BNAT1 physically binds to ERα protein. In summary, BNAT1 would play a critical role in the biology of ER-positive breast cancer by modulating ERα-dependent transcription regulation. We consider that BNAT1 could be a potential molecular target for diagnostic and therapeutic options targeting luminal-type and endocrine-resistant breast cancer.", "classifications": [ { "id": "Suzuki", "label": "Group Suzuki", "parent": "Takekawa", "type": "group" }, { "id": "Takekawa", "label": "Team Takekawa", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Kuniko", "last_name": "Horie", "name": null }, { "creator_type": "author", "first_name": "Kiyoshi", "last_name": "Takagi", "name": null }, { "creator_type": "author", "first_name": "Toshihiko", "last_name": "Takeiwa", "name": null }, { "creator_type": "author", "first_name": "Yuichi", "last_name": "Mitobe", "name": null }, { "creator_type": "author", "first_name": "Hidetaka", "last_name": "Kawabata", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Kazuhiro", "last_name": "Ikeda", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Inoue", "name": null } ], "identifiers": { "doi": { "normalized": "10.3390/cells11223610" }, "pmcid": { "normalized": "PMC9688125" }, "pmid": { "normalized": "36429038" } }, "mesh": [ { "descriptor": "Breast Neoplasms", "descriptor_ui": "D001943", "major_topic": true }, { "descriptor": "Estrogen Receptor alpha", "descriptor_ui": "D047628", "major_topic": false }, { "descriptor": "Estrogens", "descriptor_ui": "D004967", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Receptors, Estrogen", "descriptor_ui": "D011960", "major_topic": false }, { "descriptor": "RNA, Long Noncoding", "descriptor_ui": "D062085", "major_topic": true } ], "publication": { "conference_name": null, "date": "2022 Nov 15", "date_precision": "day", "issue": "22", "normalized_date": "2022-11-15", "pages": "", "proceedings_title": null, "publisher": "", "title": "Cells", "volume": "11", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Estrogen-Inducible LncRNA BNAT1 Functions as a Modulator for Estrogen Receptor Signaling in Endocrine-Resistant Breast Cancer Cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Leaf meristem is a cell proliferative zone present in the lateral organ primordia. In this study, we examined how cell proliferative zones in primordia of planar floral organs and polar auxin transport inhibitor (PATI)-treated leaf organs differ from those of non-treated foliage leaves of Arabidopsis thaliana, with a focus on the accumulation pattern of ANGUSTIFOLIA3 (AN3) protein, a key element for leaf meristem positioning. We found that PATI-induced leaf shape changes were correlated with cell division angle but not with meristem positioning/size or AN3 localisation. In contrast, different shapes between sepals and petals compared with foliage leaves were associated with both altered meristem position, due to altered AN3 expression patterns, and different distributions of cell division angles. A numerical simulation showed that meristem position majorly affected the final shape but biased cell division angles had a minor effect. Taken together, these results suggest that the unique shapes of different lateral organs depend on the position of the meristem in the case of floral organs and cell division angles in the case of leaf organs with different auxin flow.", "classifications": [ { "id": "Mochizuki", "label": "Group Mochizuki", "parent": "Eiraku", "type": "group" }, { "id": "Eiraku", "label": "Team Eiraku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Ayaka", "last_name": "Kinoshita", "name": null }, { "creator_type": "author", "first_name": "Makiko", "last_name": "Naito", "name": null }, { "creator_type": "author", "first_name": "Zining", "last_name": "Wang", "name": null }, { "creator_type": "author", "first_name": "Yasuhiro", "last_name": "Inoue", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Mochizuki", "name": null }, { "creator_type": "author", "first_name": "Hirokazu", "last_name": "Tsukaya", "name": null } ], "identifiers": { "doi": { "normalized": "10.1242/dev.199773" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "36373561" } }, "mesh": [ { "descriptor": "Arabidopsis", "descriptor_ui": "D017360", "major_topic": true }, { "descriptor": "Arabidopsis Proteins", "descriptor_ui": "D029681", "major_topic": true }, { "descriptor": "Cell Division", "descriptor_ui": "D002455", "major_topic": false }, { "descriptor": "Gene Expression Regulation, Plant", "descriptor_ui": "D018506", "major_topic": false }, { "descriptor": "Indoleacetic Acids", "descriptor_ui": "D007210", "major_topic": false }, { "descriptor": "Meristem", "descriptor_ui": "D018519", "major_topic": false }, { "descriptor": "Plant Leaves", "descriptor_ui": "D018515", "major_topic": false } ], "publication": { "conference_name": null, "date": "2022 Nov 14", "date_precision": "day", "issue": "", "normalized_date": "2022-11-14", "pages": "dev.199773", "proceedings_title": null, "publisher": "", "title": "Development (Cambridge, England)", "volume": "", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Position of meristems and the angles of the cell division plane regulate the uniqueness of lateral organ shape.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "", "classifications": [ { "id": "Suzuki", "label": "Group Suzuki", "parent": "Takekawa", "type": "group" }, { "id": "Takekawa", "label": "Team Takekawa", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Ryohei", "last_name": "Nejima", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Eguchi", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Todokoro", "name": null }, { "creator_type": "author", "first_name": "Tomoyuki", "last_name": "Inoue", "name": null }, { "creator_type": "author", "first_name": "Yuichi", "last_name": "Kaji", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Takaaki", "last_name": "Hattori", "name": null }, { "creator_type": "author", "first_name": "Saichi", "last_name": "Hoshi", "name": null }, { "creator_type": "author", "first_name": "Yumi", "last_name": "Sasaki", "name": null }, { "creator_type": "author", "first_name": "Yoshitsugu", "last_name": "Inoue", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/s10384-022-00965-6" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "36374434" } }, "mesh": [], "publication": { "conference_name": null, "date": "2022 Nov 14", "date_precision": "day", "issue": "", "normalized_date": "2022-11-14", "pages": "", "proceedings_title": null, "publisher": "", "title": "Japanese journal of ophthalmology", "volume": "", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Correction to: Analysis of treatment protocols using azithromycin eye drops for bacterial blepharitis: second report-bacteriological investigation.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Most published guidelines for genomic biomarker testing in non-small cell lung cancer (NSCLC) reflect the disease epidemiology and treatments readily available in Europe and North America. However, 60% of annual global NSCLC cases occur in Asia, where patient characteristics, tumor molecular profiles, and treatments vary greatly from the Western world. For example, mutations in the epidermal growth factor receptor (EGFR) occur at a higher prevalence in Asia than in other world regions. Although medical associations such as IASLC, ESMO, and ASCO have described principles for tumor genomic biomarker testing in NSCLC, there is a need for recommendations specific for Asia. This report provides consensus recommendations for NSCLC biomarker testing from Asian lung cancer experts, for clinicians working in Asia to improve patient care. These recommendations are divided into non-metastatic and metastatic forms of adenocarcinoma and squamous cell carcinoma. Biomarker testing approaches for actionable genetic alterations in EGFR, ALK, ROS1 and others are discussed. Owing to the higher prevalence of EGFR mutations in Asia, the experts emphasized the need for EGFR testing to include not just common mutations (exon 19 deletions & L858R substitutions) but also other uncommon EGFR mutations. In addition to the assessment of biomarkers in tumor tissue, the role of assessing tumor biomarkers by liquid biopsy are also discussed.", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Tetsuya", "last_name": "Mitsudomi", "name": null }, { "creator_type": "author", "first_name": "Daniel", "last_name": "Tan", "name": null }, { "creator_type": "author", "first_name": "James Chih-Hsin", "last_name": "Yang", "name": null }, { "creator_type": "author", "first_name": "Myung-Ju", "last_name": "Ahn", "name": null }, { "creator_type": "author", "first_name": "Ullas", "last_name": "Batra", "name": null }, { "creator_type": "author", "first_name": "Byoung-Chul", "last_name": "Cho", "name": null }, { "creator_type": "author", "first_name": "Gerardo", "last_name": "Cornelio", "name": null }, { "creator_type": "author", "first_name": "Tony", "last_name": "Lim", "name": null }, { "creator_type": "author", "first_name": "Tony", "last_name": "Mok", "name": null }, { "creator_type": "author", "first_name": "Kumar", "last_name": "Prabhash", "name": null }, { "creator_type": "author", "first_name": "Thanyanan", "last_name": "Reungwetwattana", "name": null }, { "creator_type": "author", "first_name": "Sheng-Xiang", "last_name": "Ren", "name": null }, { "creator_type": "author", "first_name": "Navneet", "last_name": "Singh", "name": null }, { "creator_type": "author", "first_name": "Shinichi", "last_name": "Toyooka", "name": null }, { "creator_type": "author", "first_name": "Yi-Long", "last_name": "Wu", "name": null }, { "creator_type": "author", "first_name": "Pan-Chyr", "last_name": "Yang", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.jtho.2022.10.021" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "36379356" } }, "mesh": [ { "descriptor": "Asia", "descriptor_ui": "D001208", "major_topic": false }, { "descriptor": "Biomarkers, Tumor", "descriptor_ui": "D014408", "major_topic": false }, { "descriptor": "Carcinoma, Non-Small-Cell Lung", "descriptor_ui": "D002289", "major_topic": true }, { "descriptor": "ErbB Receptors", "descriptor_ui": "D066246", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Lung Neoplasms", "descriptor_ui": "D008175", "major_topic": true }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": false }, { "descriptor": "Protein-Tyrosine Kinases", "descriptor_ui": "D011505", "major_topic": false }, { "descriptor": "Proto-Oncogene Proteins", "descriptor_ui": "D011518", "major_topic": false } ], "publication": { "conference_name": null, "date": "2022 Nov 12", "date_precision": "day", "issue": "", "normalized_date": "2022-11-12", "pages": "S1556-0864(22)01905-0", "proceedings_title": null, "publisher": "", "title": "Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer", "volume": "", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Expert consensus recommendations on biomarker testing in metastatic and non-metastatic non-small cell lung cancer in Asia.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: Proline/arginine-rich end leucine-rich repeat protein (PRELP) is a member of the small leucine-rich proteoglycan family of extracellular matrix proteins, which is markedly suppressed in the majority of early-stage epithelial cancers and plays a role in regulating the epithelial-mesenchymal transition by altering cell-cell adhesion. Although PRELP is an important factor in the development and progression of bladder cancer, the mechanism of PRELP gene repression remains unclear. RESULTS: Here, we show that repression of PRELP mRNA expression in bladder cancer cells is alleviated by HDAC inhibitors (HDACi) through histone acetylation. Using ChIP-qPCR analysis, we found that acetylation of lysine residue 5 of histone H2B in the PRELP gene promoter region is a marker for the de-repression of PRELP expression. CONCLUSIONS: These results suggest a mechanism through which HDACi may partially regulate the function of PRELP to suppress the development and progression of bladder cancer. Some HDACi are already in clinical use, and the findings of this study provide a mechanistic basis for further investigation of HDACi-based therapeutic strategies.", "classifications": [ { "id": "Hamamoto", "label": "Group Hamamoto", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Kanto", "last_name": "Shozu", "name": null }, { "creator_type": "author", "first_name": "Syuzo", "last_name": "Kaneko", "name": null }, { "creator_type": "author", "first_name": "Norio", "last_name": "Shinkai", "name": null }, { "creator_type": "author", "first_name": "Ai", "last_name": "Dozen", "name": null }, { "creator_type": "author", "first_name": "Hirofumi", "last_name": "Kosuge", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Nakakido", "name": null }, { "creator_type": "author", "first_name": "Hidenori", "last_name": "Machino", "name": null }, { "creator_type": "author", "first_name": "Ken", "last_name": "Takasawa", "name": null }, { "creator_type": "author", "first_name": "Ken", "last_name": "Asada", "name": null }, { "creator_type": "author", "first_name": "Masaaki", "last_name": "Komatsu", "name": null }, { "creator_type": "author", "first_name": "Kouhei", "last_name": "Tsumoto", "name": null }, { "creator_type": "author", "first_name": "Shin-Ichi", "last_name": "Ohnuma", "name": null }, { "creator_type": "author", "first_name": "Ryuji", "last_name": "Hamamoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1186/s13148-022-01370-z" }, "pmcid": { "normalized": "PMC9656081" }, "pmid": { "normalized": "36371227" } }, "mesh": [ { "descriptor": "Acetylation", "descriptor_ui": "D000107", "major_topic": false }, { "descriptor": "DNA Methylation", "descriptor_ui": "D019175", "major_topic": false }, { "descriptor": "Extracellular Matrix Proteins", "descriptor_ui": "D016326", "major_topic": false }, { "descriptor": "Glycoproteins", "descriptor_ui": "D006023", "major_topic": false }, { "descriptor": "Histone Deacetylase Inhibitors", "descriptor_ui": "D056572", "major_topic": false }, { "descriptor": "Histones", "descriptor_ui": "D006657", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Lysine", "descriptor_ui": "D008239", "major_topic": false }, { "descriptor": "Urinary Bladder Neoplasms", "descriptor_ui": "D001749", "major_topic": true } ], "publication": { "conference_name": null, "date": "2022 Nov 12", "date_precision": "day", "issue": "1", "normalized_date": "2022-11-12", "pages": "147", "proceedings_title": null, "publisher": "", "title": "Clinical epigenetics", "volume": "14", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Repression of the PRELP gene is relieved by histone deacetylase inhibitors through acetylation of histone H2B lysine 5 in bladder cancer.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "INTRODUCTION: Advances in metabolomics have significantly improved cancer detection, diagnosis, treatment, and prognosis. OBJECTIVES: To investigate the relationship between metabolic tumor volume (MTV) using 2-deoxy-2-[(18)F]fluoro-D-glucose (FDG) positron emission tomography (PET)/ computed tomography (CT) and metabolomics data in patients with colorectal cancer (CRC). METHODS: The metabolome in tumor tissues was analyzed using capillary electrophoresis time-of-flight mass spectrometry in 33 patients with newly diagnosed CRC who underwent FDG PET/CT before treatment and had tumor tissue post-surgery. Based on the FDG PET data, MTV was calculated and was dichotomized according to the median value, and tumors were divided into low-MTV and high-MTV tumors. Metabolomics data were compared between the low-MTV and high-MTV tumors. RESULTS: The levels of most glycolysis-related metabolites were not different between low-MTV and high-MTV tumors. The level of component of the initial part of the tricarboxylic acid (TCA) cycle, citrate, was significantly lower in the high-MTV tumor than in the low-MTV tumor. The TCA intermediate succinate level was significantly higher in the high-MTV tumor than in the low-MTV tumor. In contrast, the TCA intermediate fumarate level was significantly lower in the high-MTV tumor than in the low-MTV tumor. The levels of many amino acids were significantly higher in the high-MTV tumor than in the low-MTV tumor. CONCLUSIONS: Although preliminary, these results suggest that tumors with high FDG metabolism in CRC may obtain more energy by using a reverse reaction of the TCA cycle and amino-acid metabolism. However, further research is required to clarify this relationship.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Masashi", "last_name": "Imajo", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Norikane", "name": null }, { "creator_type": "author", "first_name": "Yuka", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Yukito", "last_name": "Maeda", "name": null }, { "creator_type": "author", "first_name": "Kaori", "last_name": "Saitoh", "name": null }, { "creator_type": "author", "first_name": "Keiko", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Keiichi", "last_name": "Okano", "name": null }, { "creator_type": "author", "first_name": "Yoshihiro", "last_name": "Nishiyama", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/s11306-022-01952-1" }, "pmcid": { "normalized": "PMC9652241" }, "pmid": { "normalized": "36367606" } }, "mesh": [ { "descriptor": "Colorectal Neoplasms", "descriptor_ui": "D015179", "major_topic": true }, { "descriptor": "Fluorodeoxyglucose F18", "descriptor_ui": "D019788", "major_topic": false }, { "descriptor": "Glucose", "descriptor_ui": "D005947", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Metabolomics", "descriptor_ui": "D055432", "major_topic": false }, { "descriptor": "Positron Emission Tomography Computed Tomography", "descriptor_ui": "D000072078", "major_topic": true } ], "publication": { "conference_name": null, "date": "2022 Nov 11", "date_precision": "day", "issue": "11", "normalized_date": "2022-11-11", "pages": "91", "proceedings_title": null, "publisher": "", "title": "Metabolomics : Official journal of the Metabolomic Society", "volume": "18", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Relationship between [(18)F]FDG PET/CT and metabolomics in patients with colorectal cancer.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Anti-oxidative intraocular irrigating solutions (IISs) based on reactive persulfides, such as oxidized glutathione disulfide (GSSG), are commonly used worldwide. However, even with GSSG-based IISs, it has been shown that oxidative stress can occur during surgery, posing a risk to intraocular tissues. This study compared two IISs: one containing GSSG and one containing an oxidized glutathione trisulfide (GSSSG). Experimental in vivo irrigation with the IISs in rabbits showed that there was less leakage into the anterior chamber of rabbit serum albumin during perfusion with a 300-muM GSSSG IIS than with a 300-muM GSSG IIS. Experimental in vivo cataract surgery in rabbits showed that aqueous flare was suppressed 3 days after surgery with a 600-muM GSSSG IIS, but not with a 300-muM GSSSG or 300-muM GSSG IIS. Furthermore, an in vitro experiment, without any live tissue, showed that reactive oxygen species were suppressed more strongly with a 600-muM GSSSG IIS than with a 300-muM GSSG IIS. Thus, this study found that novel IISs based on GSSSG had anti-inflammatory and anti-oxidative effects during and after intraocular surgery and may decrease the rate of complications after surgery.", "classifications": [ { "id": "Akaike", "label": "Group Akaike", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Kunikata", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Tawarayama", "name": null }, { "creator_type": "author", "first_name": "Satoru", "last_name": "Tsuda", "name": null }, { "creator_type": "author", "first_name": "Takaaki", "last_name": "Akaike", "name": null }, { "creator_type": "author", "first_name": "Toru", "last_name": "Nakazawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41598-022-21677-4" }, "pmcid": { "normalized": "PMC9649782" }, "pmid": { "normalized": "36357454" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Aqueous Humor", "descriptor_ui": "D001082", "major_topic": false }, { "descriptor": "Cataract Extraction", "descriptor_ui": "D002387", "major_topic": true }, { "descriptor": "Glutathione", "descriptor_ui": "D005978", "major_topic": false }, { "descriptor": "Glutathione Disulfide", "descriptor_ui": "D019803", "major_topic": false }, { "descriptor": "Rabbits", "descriptor_ui": "D011817", "major_topic": false }, { "descriptor": "Sulfides", "descriptor_ui": "D013440", "major_topic": true } ], "publication": { "conference_name": null, "date": "2022 Nov 10", "date_precision": "day", "issue": "1", "normalized_date": "2022-11-10", "pages": "19243", "proceedings_title": null, "publisher": "", "title": "Scientific reports", "volume": "12", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Development of an anti-oxidative intraocular irrigating solution based on reactive persulfides.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Lymph node metastasis (LNM) is a well-established prognostic factor in endometrial cancer (EC). We aimed to construct a model that predicts LNM and prognosis using preoperative factors such as myometrial invasion (MI), enlarged lymph nodes (LNs), histological grade determined by endometrial biopsy, and serum cancer antigen 125 (CA125) level using two independent cohorts consisting of 254 EC patients. The area under the receiver operating characteristic curve (AUC) of the constructed model was 0.80 regardless of the machine learning techniques. Enlarged LNs and higher serum CA125 levels were more significant in patients with low-grade EC (LGEC) and LNM than in patients without LNM, whereas deep MI and higher CA125 levels were more significant in patients with high-grade EC (HGEC) and LNM than in patients without LNM. The predictive performance of LNM in the HGEC group was higher than that in the LGEC group (AUC = 0.84 and 0.75, respectively). Patients in the group without postoperative pathological LNM and positive LNM prediction had significantly worse relapse-free and overall survival than patients with negative LNM prediction (log-rank test, P < 0.01). This study showed that preoperative clinicopathological factors can predict LNM with high precision and detect patients with poor prognoses. Furthermore, clinicopathological factors associated with LNM were different between HGEC and LGEC patients.", "classifications": [ { "id": "Hamamoto", "label": "Group Hamamoto", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yuka", "last_name": "Asami", "name": null }, { "creator_type": "author", "first_name": "Kengo", "last_name": "Hiranuma", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Takayanagi", "name": null }, { "creator_type": "author", "first_name": "Maiko", "last_name": "Matsuda", "name": null }, { "creator_type": "author", "first_name": "Yoko", "last_name": "Shimada", "name": null }, { "creator_type": "author", "first_name": "Mayumi Kobayashi", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Ikumi", "last_name": "Kuno", "name": null }, { "creator_type": "author", "first_name": "Naoya", "last_name": "Murakami", "name": null }, { "creator_type": "author", "first_name": "Masaaki", "last_name": "Komatsu", "name": null }, { "creator_type": "author", "first_name": "Ryuji", "last_name": "Hamamoto", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Kohno", "name": null }, { "creator_type": "author", "first_name": "Akihiko", "last_name": "Sekizawa", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Matsumoto", "name": null }, { "creator_type": "author", "first_name": "Tomoyasu", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Kouya", "last_name": "Shiraishi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41598-022-23252-3" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "36347927" } }, "mesh": [ { "descriptor": "Endometrial Neoplasms", "descriptor_ui": "D016889", "major_topic": true }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Lymph Nodes", "descriptor_ui": "D008198", "major_topic": true }, { "descriptor": "Lymphatic Metastasis", "descriptor_ui": "D008207", "major_topic": false }, { "descriptor": "Neoplasm Recurrence, Local", "descriptor_ui": "D009364", "major_topic": false }, { "descriptor": "Prognosis", "descriptor_ui": "D011379", "major_topic": false }, { "descriptor": "Retrospective Studies", "descriptor_ui": "D012189", "major_topic": false } ], "publication": { "conference_name": null, "date": "2022 Nov 8", "date_precision": "day", "issue": "1", "normalized_date": "2022-11-08", "pages": "19004", "proceedings_title": null, "publisher": "", "title": "Scientific reports", "volume": "12", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Predictive model for the preoperative assessment and prognostic modeling of lymph node metastasis in endometrial cancer.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Control problems with incomplete information and memory limitation appear in many practical situations. Although partially observable stochastic control (POSC) is a conventional theoretical framework that considers the optimal control problem with incomplete information, it cannot consider memory limitation. Furthermore, POSC cannot be solved in practice except in special cases. In order to address these issues, we propose an alternative theoretical framework, memory-limited POSC (ML-POSC). ML-POSC directly considers memory limitation as well as incomplete information, and it can be solved in practice by employing the technique of mean-field control theory. ML-POSC can generalize the linear-quadratic-Gaussian (LQG) problem to include memory limitation. Because estimation and control are not clearly separated in the LQG problem with memory limitation, the Riccati equation is modified to the partially observable Riccati equation, which improves estimation as well as control. Furthermore, we demonstrate the effectiveness of ML-POSC for a non-LQG problem by comparing it with the local LQG approximation.", "classifications": [ { "id": "Kobayashi", "label": "Group Kobayashi", "parent": "Wakamoto", "type": "group" }, { "id": "Wakamoto", "label": "Team Wakamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Takehiro", "last_name": "Tottori", "name": null }, { "creator_type": "author", "first_name": "Tetsuya J.", "last_name": "Kobayashi", "name": null } ], "identifiers": { "doi": { "normalized": "10.3390/e24111599" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "36359688" } }, "mesh": [], "publication": { "conference_name": null, "date": "2022 Nov 3", "date_precision": "day", "issue": "11", "normalized_date": "2022-11-03", "pages": "1599", "proceedings_title": null, "publisher": "", "title": "Entropy (Basel, Switzerland)", "volume": "24", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Memory-Limited Partially Observable Stochastic Control and Its Mean-Field Control Approach.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "In chemical biology research, various fluorescent probes have been developed and used to visualize target proteins or molecules in living cells and tissues, yet there are limitations to this technology, such as the limited number of colors that can be detected simultaneously. Recently, Raman spectroscopy has been applied in chemical biology to overcome such limitations. Raman spectroscopy detects the molecular vibrations reflecting the structures and chemical conditions of molecules in a sample and was originally used to directly visualize the chemical responses of endogenous molecules. However, our initial research to develop “Raman tags” opens a new avenue for the application of Raman spectroscopy in chemical biology. In this Perspective, we first introduce the label-free Raman imaging of biomolecules, illustrating the biological applications of Raman spectroscopy. Next, we highlight the application of Raman imaging of small molecules using Raman tags for chemical biology research. Finally, we discuss the development and potential of Raman probes, which represent the next-generation probes in chemical biology.", "classifications": [ { "id": "JPMJCR1925", "label": "JPMJCR1925", "researcher": "Katsumasa Fujita", "type": "grant" }, { "id": "Fujita", "label": "Group Fujita", "parent": "Fujita", "type": "group" }, { "id": "Sodeoka", "label": "Group Sodeoka", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Kosuke", "last_name": "Dodo", "name": null }, { "creator_type": "author", "first_name": "Katsumasa", "last_name": "Fujita", "name": null }, { "creator_type": "author", "first_name": "Mikiko", "last_name": "Sodeoka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/jacs.2c05359" }, "pmcid": { "normalized": null }, "pmid": { "normalized": null } }, "mesh": [], "publication": { "conference_name": null, "date": "2022-11-02", "date_precision": "day", "issue": "43", "normalized_date": "2022-11-02", "pages": "19651-19667", "proceedings_title": null, "publisher": "American Chemical Society", "title": "Journal of the American Chemical Society", "volume": "144", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Raman Spectroscopy for Chemical Biology Research", "url": "https://doi.org/10.1021/jacs.2c05359", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Invasive mucinous adenocarcinoma (IMA) of the lung shares some clinicopathological features with mucinous carcinoma of other organs, such as the ovary. Sarcoma-like lesions, called mural nodules, have been reported in the cystic walls of ovarian mucinous tumors. In this study, we analyzed 213 surgically resected cases of IMA of the lung to determine whether similar mural nodule-like lesions were present. We considered abrupt discrete lesions composed of dedifferentiated tumor cells as mural nodule-like lesions. Of 213 IMAs, we identified 11 tumors with mural nodule-like lesions that were histologically categorized into three subtypes similar to those in the ovary. The sarcomatoid and anaplastic carcinoma-like nodules were composed of spindle cell proliferations and polygonal undifferentiated carcinoma, respectively. Sarcoma-like lesions mimicked sarcomatoid nodules, but the spindle cell proliferations were considered a fibroblastic reaction to the scattered, isolated clusters of tumor cells. Molecular analysis of the components of differentiated IMAs and mural nodule-like lesions revealed a clonal relationship, suggesting a spectrum of tumors with different histology. Clinicopathologically, an older age, the male sex, and smokers were significantly associated with IMAs with mural nodule-like lesions. Notably, patient outcomes were unaffected by the presence or absence of these lesions. Our findings demonstrated that IMA of the lung rarely develops mural nodule-like lesions (11 of 213, 5%). Despite a histological impression of clinical aggressiveness, there was no clear trend in patient outcomes, suggesting that pathologists should avoid overstating this mural nodule-like lesion.", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Masahiro", "last_name": "Higashiyama", "name": null }, { "creator_type": "author", "first_name": "Yoshihisa", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Jumpei", "last_name": "Kashima", "name": null }, { "creator_type": "author", "first_name": "Yuji", "last_name": "Muraoka", "name": null }, { "creator_type": "author", "first_name": "Hirokazu", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Masahiko", "last_name": "Kusumoto", "name": null }, { "creator_type": "author", "first_name": "Shun-Ichi", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null } ], "identifiers": { "doi": { "normalized": "10.1097/pas.0000000000001938" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "35939825" } }, "mesh": [ { "descriptor": "Adenocarcinoma, Mucinous", "descriptor_ui": "D002288", "major_topic": true }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Lung", "descriptor_ui": "D008168", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Ovarian Neoplasms", "descriptor_ui": "D010051", "major_topic": true }, { "descriptor": "Sarcoma", "descriptor_ui": "D012509", "major_topic": true }, { "descriptor": "Soft Tissue Neoplasms", "descriptor_ui": "D012983", "major_topic": true } ], "publication": { "conference_name": null, "date": "2022 Nov 1", "date_precision": "day", "issue": "11", "normalized_date": "2022-11-01", "pages": "1524-1532", "proceedings_title": null, "publisher": "", "title": "The American journal of surgical pathology", "volume": "46", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Invasive Mucinous Adenocarcinoma of the Lung With a Mural Nodule-like Lesion.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Since U.S. President Barack Obama announced the Precision Medicine Initiative in his New Year's State of the Union address in 2015, the establishment of a precision medicine system has been emphasized worldwide, particularly in the field of oncology. With the advent of next-generation sequencers specifically, genome analysis technology has made remarkable progress, and there are active efforts to apply genome information to diagnosis and treatment. Generally, in the process of feeding back the results of next-generation sequencing analysis to patients, a molecular tumor board (MTB), consisting of experts in clinical oncology, genetic medicine, etc., is established to discuss the results. On the other hand, an MTB currently involves a large amount of work, with humans searching through vast databases and literature, selecting the best drug candidates, and manually confirming the status of available clinical trials. In addition, as personalized medicine advances, the burden on MTB members is expected to increase in the future. Under these circumstances, introducing cutting-edge artificial intelligence (AI) technology and information and communication technology to MTBs while reducing the burden on MTB members and building a platform that enables more accurate and personalized medical care would be of great benefit to patients. In this review, we introduced the latest status of elemental technologies that have potential for AI utilization in MTB, and discussed issues that may arise in the future as we progress with AI implementation.", "classifications": [ { "id": "Hamamoto", "label": "Group Hamamoto", "parent": "Okamoto", "type": "group" }, { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Ryuji", "last_name": "Hamamoto", "name": null }, { "creator_type": "author", "first_name": "Takafumi", "last_name": "Koyama", "name": null }, { "creator_type": "author", "first_name": "Nobuji", "last_name": "Kouno", "name": null }, { "creator_type": "author", "first_name": "Tomohiro", "last_name": "Yasuda", "name": null }, { "creator_type": "author", "first_name": "Shuntaro", "last_name": "Yui", "name": null }, { "creator_type": "author", "first_name": "Kazuki", "last_name": "Sudo", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Hirata", "name": null }, { "creator_type": "author", "first_name": "Kuniko", "last_name": "Sunami", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Kubo", "name": null }, { "creator_type": "author", "first_name": "Ken", "last_name": "Takasawa", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Hidenori", "last_name": "Machino", "name": null }, { "creator_type": "author", "first_name": "Kazuma", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Ken", "last_name": "Asada", "name": null }, { "creator_type": "author", "first_name": "Masaaki", "last_name": "Komatsu", "name": null }, { "creator_type": "author", "first_name": "Syuzo", "last_name": "Kaneko", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null }, { "creator_type": "author", "first_name": "Noboru", "last_name": "Yamamoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1186/s40164-022-00333-7" }, "pmcid": { "normalized": "PMC9620610" }, "pmid": { "normalized": "36316731" } }, "mesh": [], "publication": { "conference_name": null, "date": "2022 Oct 31", "date_precision": "day", "issue": "1", "normalized_date": "2022-10-31", "pages": "82", "proceedings_title": null, "publisher": "", "title": "Experimental hematology & oncology", "volume": "11", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Introducing AI to the molecular tumor board: one direction toward the establishment of precision medicine using large-scale cancer clinical and biological information.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The histone methyltransferase SET domain-containing protein 8 (SETD8), which methylates histone H4 lysine 20 (H4K20) and non-histone proteins such as p53, plays key roles in human carcinogenesis. Our aim was to determine the involvement of SETD8 in endometrial cancer and its therapeutic potential and identify the downstream genes regulated by SETD8 via H4K20 methylation and the p53 signaling pathway. We examined the expression profile of SETD8 and evaluated whether SETD8 plays a critical role in the proliferation of endometrial cancer cells using small interfering RNAs (siRNAs). We identified the prognostically important genes regulated by SETD8 via H4K20 methylation and p53 signaling using chromatin immunoprecipitation sequencing, RNA sequencing, and machine learning. We confirmed that SETD8 expression was elevated in endometrial cancer tissues. Our in vitro results suggest that the suppression of SETD8 using siRNA or a selective inhibitor attenuated cell proliferation and promoted the apoptosis of endometrial cancer cells. In these cells, SETD8 regulates genes via H4K20 methylation and the p53 signaling pathway. We also identified the prognostically important genes related to apoptosis, such as those encoding KIAA1324 and TP73, in endometrial cancer. SETD8 is an important gene for carcinogenesis and progression of endometrial cancer via H4K20 methylation.", "classifications": [ { "id": "Hamamoto", "label": "Group Hamamoto", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Asako", "last_name": "Kukita", "name": null }, { "creator_type": "author", "first_name": "Kenbun", "last_name": "Sone", "name": null }, { "creator_type": "author", "first_name": "Syuzo", "last_name": "Kaneko", "name": null }, { "creator_type": "author", "first_name": "Eiryo", "last_name": "Kawakami", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Oki", "name": null }, { "creator_type": "author", "first_name": "Machiko", "last_name": "Kojima", "name": null }, { "creator_type": "author", "first_name": "Miku", "last_name": "Wada", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Toyohara", "name": null }, { "creator_type": "author", "first_name": "Yu", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Futaba", "last_name": "Inoue", "name": null }, { "creator_type": "author", "first_name": "Saki", "last_name": "Tanimoto", "name": null }, { "creator_type": "author", "first_name": "Ayumi", "last_name": "Taguchi", "name": null }, { "creator_type": "author", "first_name": "Tomohiko", "last_name": "Fukuda", "name": null }, { "creator_type": "author", "first_name": "Yuichiro", "last_name": "Miyamoto", "name": null }, { "creator_type": "author", "first_name": "Michihiro", "last_name": "Tanikawa", "name": null }, { "creator_type": "author", "first_name": "Mayuyo", "last_name": "Mori-Uchino", "name": null }, { "creator_type": "author", "first_name": "Tetsushi", "last_name": "Tsuruga", "name": null }, { "creator_type": "author", "first_name": "Takayuki", "last_name": "Iriyama", "name": null }, { "creator_type": "author", "first_name": "Yoko", "last_name": "Matsumoto", "name": null }, { "creator_type": "author", "first_name": "Kazunori", "last_name": "Nagasaka", "name": null }, { "creator_type": "author", "first_name": "Osamu", "last_name": "Wada-Hiraike", "name": null }, { "creator_type": "author", "first_name": "Katsutoshi", "last_name": "Oda", "name": null }, { "creator_type": "author", "first_name": "Ryuji", "last_name": "Hamamoto", "name": null }, { "creator_type": "author", "first_name": "Yutaka", "last_name": "Osuga", "name": null } ], "identifiers": { "doi": { "normalized": "10.3390/cancers14215367" }, "pmcid": { "normalized": "PMC9655767" }, "pmid": { "normalized": "36358786" } }, "mesh": [], "publication": { "conference_name": null, "date": "2022 Oct 31", "date_precision": "day", "issue": "21", "normalized_date": "2022-10-31", "pages": "5367", "proceedings_title": null, "publisher": "", "title": "Cancers", "volume": "14", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "The Histone Methyltransferase SETD8 Regulates the Expression of Tumor Suppressor Genes via H4K20 Methylation and the p53 Signaling Pathway in Endometrial Cancer Cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Visible light, particularly in the blue region of the spectrum, can cause cell dysfunction through the generation of singlet oxygen, contributing to cellular aging and age-related pathologies. Although photooxidation of nucleic acids, lipids, and amino acids has been extensively studied, the magnitude and span of blue-light-induced protein damages within proteome remain largely unknown. Herein we present a chemoproteomic approach to mapping blue-light-damaged proteins in live mammalian cells by exploiting a nucleophilic alkyne chemical probe. A gene ontology enrichment analysis revealed that cell surface proteins are more readily oxidized than other susceptible sets of proteins, including mitochondrial proteins. In particular, the integrin family of cell surface receptors (ITGs) was highly ranked in the mammalian cells tested, including human corneal endothelial cells. The blue-light-oxidized ITGB1 protein was functionally inactive in promoting cell adhesion and proliferation, suggesting that the photodamage of integrins contributes to the blue-light-induced cell dysfunction. Further application of our method to various cells and tissues should lead to a comprehensive analysis of light-sensitive proteins.", "classifications": [ { "id": "Sodeoka", "label": "Group Sodeoka", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Kohei", "last_name": "Toh", "name": null }, { "creator_type": "author", "first_name": "Kosuke", "last_name": "Nishio", "name": null }, { "creator_type": "author", "first_name": "Reiko", "last_name": "Nakagawa", "name": null }, { "creator_type": "author", "first_name": "Syusuke", "last_name": "Egoshi", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Abo", "name": null }, { "creator_type": "author", "first_name": "Amelie", "last_name": "Perron", "name": null }, { "creator_type": "author", "first_name": "Shin-ichi", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Naoki", "last_name": "Okumura", "name": null }, { "creator_type": "author", "first_name": "Noriko", "last_name": "Koizumi", "name": null }, { "creator_type": "author", "first_name": "Kosuke", "last_name": "Dodo", "name": null }, { "creator_type": "author", "first_name": "Mikiko", "last_name": "Sodeoka", "name": null }, { "creator_type": "author", "first_name": "Motonari", "last_name": "Uesugi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/jacs.2c07180" }, "pmcid": { "normalized": null }, "pmid": { "normalized": null } }, "mesh": [], "publication": { "conference_name": null, "date": "2022-10-28", "date_precision": "day", "issue": "", "normalized_date": "2022-10-28", "pages": "", "proceedings_title": null, "publisher": "American Chemical Society", "title": "Journal of the American Chemical Society", "volume": "", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Chemoproteomic Identification of Blue-Light-Damaged Proteins", "url": "https://doi.org/10.1021/jacs.2c07180", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Thymic squamous cell carcinoma (TSC) presents distinct immunohistochemical features with its expression of CD5 and CD117, both of which are rarely expressed in squamous cell carcinoma in other organs. We found insulinoma-associated-1 (INSM1) expression in some TSCs; thus, a series of thymic tumors were examined retrospectively. Using surgically resected thymic tumors (TSC, n = 35; thymic atypical carcinoid [TAC], n = 4; and thymoma, n = 112) and non-neoplastic thymic tissue (n = 26), we evaluated immunohistochemically the expressions of INSM1, ASCL1, SOX2, NE markers (synaptophysin, chromogranin A, and CD56), and conventional TSC markers (CD5 and CD117). INSM1 was expressed in 22 TSCs (63%), whereas the positive frequencies of synaptophysin, chromogranin A, and CD56 were limited to 13, 10, and 1 cases, respectively. The discordance was highly contrasted with concordantly positive TACs. INSM1 and NE makers were rarely expressed in thymomas. INSM1 expression in TSCs was also associated with CD5 expression, which was significantly less frequent in INSM1-negative TSCs. INSM1, ASCL1, and SOX2 expressions were correlated with one another, but none of the single transcription factors or their combinations is associated with NE expression. The non-neoplastic medullary thymic epithelium was dispersedly positive for INSM1, particularly around Hassall's corpuscles. Despite positive INSM1, a significant decrease in the frequency of NE maker expression may present as a diagnostic pitfall in TSCs. Furthermore, the discordance, which was inherent in the non-neoplastic thymic epithelium, might be a characteristic feature in TSCs.", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Jumpei", "last_name": "Kashima", "name": null }, { "creator_type": "author", "first_name": "Taiki", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Akihiko", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Goto", "name": null }, { "creator_type": "author", "first_name": "Tetsuo", "last_name": "Ushiku", "name": null }, { "creator_type": "author", "first_name": "Yuichiro", "last_name": "Ohe", "name": null }, { "creator_type": "author", "first_name": "Shun-Ichi", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/s00428-022-03437-x" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "36305944" } }, "mesh": [ { "descriptor": "Biomarkers, Tumor", "descriptor_ui": "D014408", "major_topic": false }, { "descriptor": "Carcinoma, Squamous Cell", "descriptor_ui": "D002294", "major_topic": true }, { "descriptor": "Chromogranin A", "descriptor_ui": "D053379", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Immunohistochemistry", "descriptor_ui": "D007150", "major_topic": false }, { "descriptor": "Repressor Proteins", "descriptor_ui": "D012097", "major_topic": false }, { "descriptor": "Retrospective Studies", "descriptor_ui": "D012189", "major_topic": false }, { "descriptor": "Thymoma", "descriptor_ui": "D013945", "major_topic": true }, { "descriptor": "Thymus Neoplasms", "descriptor_ui": "D013953", "major_topic": true } ], "publication": { "conference_name": null, "date": "2022 Oct 28", "date_precision": "day", "issue": "", "normalized_date": "2022-10-28", "pages": "", "proceedings_title": null, "publisher": "", "title": "Virchows Archiv : an international journal of pathology", "volume": "", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Insulinoma-associated-1 (INSM1) expression in thymic squamous cell carcinoma.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The stimulation of photosynthesis is a strategy for achieving sustainable plant production. Red light is useful for plant growth because it is absorbed by chlorophyll pigments, which initiate natural photosynthetic processes. Ultraviolet (UV)-to-red wavelength-converting materials are promising candidates for eco-friendly plant cultures that do not require electric power. In this study, transparent films equipped with a UV-to-red wavelength-converting luminophore, the Eu(3+) complex, were prepared on commercially available plastic films for plant growth experiments. The present Eu(3+)-based films absorb UV light and exhibit strong red luminescence under sunlight. Eu(3+)-painted films provide significant growth acceleration with size increment and biomass production for vegetal crops and trees in a northern region. The plants cultured with Eu(3+)-painted films had a 1.2-fold height and 1.4-fold total body biomass than those cultures without the Eu(3+) luminophores. The present film can promote the plant production in fields of agriculture and forestry.", "classifications": [ { "id": "Suzuki", "label": "Group Suzuki", "parent": "Takekawa", "type": "group" }, { "id": "Takekawa", "label": "Team Takekawa", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Sunao", "last_name": "Shoji", "name": null }, { "creator_type": "author", "first_name": "Hideyuki", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Yutaka", "last_name": "Jitsuyama", "name": null }, { "creator_type": "author", "first_name": "Kotono", "last_name": "Tomita", "name": null }, { "creator_type": "author", "first_name": "Qiang", "last_name": "Haoyang", "name": null }, { "creator_type": "author", "first_name": "Yukiho", "last_name": "Sakurai", "name": null }, { "creator_type": "author", "first_name": "Yuhei", "last_name": "Okazaki", "name": null }, { "creator_type": "author", "first_name": "Kota", "last_name": "Aikawa", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Konishi", "name": null }, { "creator_type": "author", "first_name": "Kensei", "last_name": "Sasaki", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Fushimi", "name": null }, { "creator_type": "author", "first_name": "Yuichi", "last_name": "Kitagawa", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Yasuchika", "last_name": "Hasegawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41598-022-21427-6" }, "pmcid": { "normalized": "PMC9605945" }, "pmid": { "normalized": "36289255" } }, "mesh": [ { "descriptor": "Acceleration", "descriptor_ui": "D000054", "major_topic": false }, { "descriptor": "Chlorophyll", "descriptor_ui": "D002734", "major_topic": true }, { "descriptor": "Crops, Agricultural", "descriptor_ui": "D018556", "major_topic": false }, { "descriptor": "Photosynthesis", "descriptor_ui": "D010788", "major_topic": true }, { "descriptor": "Plastics", "descriptor_ui": "D010969", "major_topic": false }, { "descriptor": "Ultraviolet Rays", "descriptor_ui": "D014466", "major_topic": false } ], "publication": { "conference_name": null, "date": "2022 Oct 26", "date_precision": "day", "issue": "1", "normalized_date": "2022-10-26", "pages": "17155", "proceedings_title": null, "publisher": "", "title": "Scientific reports", "volume": "12", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Plant growth acceleration using a transparent Eu(3+)-painted UV-to-red conversion film.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Sterol regulatory element binding proteins (SREBPs) are master transcription factors for lipid synthesis, and SREBP-1 is important for fatty acid and triglyceride synthesis. SREBP-1 has two isoforms, SREBP-1a and SREBP-1c, which are splicing variants transcribed from the Srebf1 gene. Although SREBP-1a exhibits stronger transcriptional activity as compared to SREBP-1c, hepatic SREBP-1c is considered more physiologically important. We generated SREBP-1a flox mice using the CRISPR/Cas9 system, and hepatocyte- and macrophage-specific SREBP-1a knockout (KO) mice (LKO, liver-knockout; and mΦKO, macrophage-knockout). There were no significantly differences among all the mouse genotypes upon feeding with a normal diet. However, feeding with a methionine and choline-deficient (MCD) diet resulted in exacerbated liver injury in both KO mice. In LKO mice, fatty liver was unexpectedly exacerbated, leading to macrophage infiltration and inflammation. In contrast, in mΦKO mice, the fatty liver state was similar to that in flox mice, but the polarity of the macrophages in the liver was transformed into a proinflammatory M1 subtype, resulting in the exacerbation of inflammation. Taken together, we found that SREBP-1a does not contribute to hepatic lipogenesis, but in either hepatocytes or macrophages distinctly controls the onset of pathological conditions in MCD diet-induced hepatitis.", "classifications": [ { "id": "Miyamoto", "label": "Group Miyamoto", "parent": "Wakamoto", "type": "group" }, { "id": "Wakamoto", "label": "Team Wakamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Masaya", "last_name": "Araki", "name": null }, { "creator_type": "author", "first_name": "Yoshimi", "last_name": "Nakagawa", "name": null }, { "creator_type": "author", "first_name": "Hodaka", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Yasunari", "last_name": "Yamada", "name": null }, { "creator_type": "author", "first_name": "Song-iee", "last_name": "Han", "name": null }, { "creator_type": "author", "first_name": "Yuhei", "last_name": "Mizunoe", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Ohno", "name": null }, { "creator_type": "author", "first_name": "Takafumi", "last_name": "Miyamoto", "name": null }, { "creator_type": "author", "first_name": "Motohiro", "last_name": "Sekiya", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Matsuzaka", "name": null }, { "creator_type": "author", "first_name": "Hirohito", "last_name": "Sone", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Shimano", "name": null } ], "identifiers": { "doi": { "normalized": "10.1152/ajpgi.00090.2022" }, "pmcid": { "normalized": null }, "pmid": { "normalized": null } }, "mesh": [], "publication": { "conference_name": null, "date": "2022-10-25", "date_precision": "day", "issue": "", "normalized_date": "2022-10-25", "pages": "", "proceedings_title": null, "publisher": "American Physiological Society", "title": "American Journal of Physiology-Gastrointestinal and Liver Physiology", "volume": "", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Hepatocyte or macrophage-specific SREBP-1a deficiency in mice exacerbates methionine- and choline-deficient diet-induced NAFLD", "url": "https://journals.physiology.org/doi/abs/10.1152/ajpgi.00090.2022", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Primary aldosteronism (PA) is considered the most common form of secondary hypertension, which is associated with excessive aldosterone secretion in the adrenal cortex. The cause of excessive aldosterone secretion is the induction of aldosterone synthase gene (CYP11B2) expression by depolarization of adrenocortical cells. In this study, we found that YM750, an Acyl-coenzyme A: cholesterol acyltransferase (ACAT) inhibitor, acts on adrenocortical cells to suppress CYP11B2 gene expression and aldosterone secretion. YM750 inhibited the induction of CYP11B2 gene expression by KCl stimulation, but not by angiotensin II and forskolin stimulation. Interestingly, YM750 did not inhibit KCl-stimulated depolarization via an increase in intracellular calcium ion concentration. Moreover, ACAT1 expression was relatively abundant in the zona glomerulosa (ZG) including these CYP11B2-positive cells. Thus, YM750 suppresses CYP11B2 gene expression by suppressing intracellular signaling activated by depolarization. In addition, ACAT1 was suggested to play an important role in steroidogenesis in the ZG. YM750 suppresses CYP11B2 gene expression and aldosterone secretion in the adrenal cortex, suggesting that it may be a potential therapeutic agent for PA.", "classifications": [ { "id": "Suzuki", "label": "Group Suzuki", "parent": "Takekawa", "type": "group" }, { "id": "Takekawa", "label": "Team Takekawa", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Hiroki", "last_name": "Shimada", "name": null }, { "creator_type": "author", "first_name": "Shuko", "last_name": "Hata", "name": null }, { "creator_type": "author", "first_name": "Yuto", "last_name": "Yamazaki", "name": null }, { "creator_type": "author", "first_name": "Yuri", "last_name": "Otsubo", "name": null }, { "creator_type": "author", "first_name": "Ikuko", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Kazue", "last_name": "Ise", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Yokoyama", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Hironobu", "last_name": "Sasano", "name": null }, { "creator_type": "author", "first_name": "Akira", "last_name": "Sugawara", "name": null }, { "creator_type": "author", "first_name": "Yasuhiro", "last_name": "Nakamura", "name": null } ], "identifiers": { "doi": { "normalized": "10.3390/ijms232112803" }, "pmcid": { "normalized": "PMC9655524" }, "pmid": { "normalized": "36361592" } }, "mesh": [ { "descriptor": "Acyltransferases", "descriptor_ui": "D000217", "major_topic": false }, { "descriptor": "Adrenal Cortex", "descriptor_ui": "D000302", "major_topic": true }, { "descriptor": "Aldosterone", "descriptor_ui": "D000450", "major_topic": false }, { "descriptor": "Cytochrome P-450 CYP11B2", "descriptor_ui": "D019405", "major_topic": true }, { "descriptor": "Zona Glomerulosa", "descriptor_ui": "D015384", "major_topic": false } ], "publication": { "conference_name": null, "date": "2022 Oct 24", "date_precision": "day", "issue": "21", "normalized_date": "2022-10-24", "pages": "", "proceedings_title": null, "publisher": "", "title": "International journal of molecular sciences", "volume": "23", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "YM750, an ACAT Inhibitor, Acts on Adrenocortical Cells to Inhibit Aldosterone Secretion Due to Depolarization.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The CRISPR-Cas system is widely used for genome editing of cultured cells and organisms. The discovery of a new single RNA-guided endonuclease, CRISPR-Cas12a, in addition to the conventional CRISPR-Cas9 has broadened the number of editable target sites on the genome. Here, we developed an in vivo cleavable donor plasmid for precise targeted knock-in of external DNA by both Cas9 and Cas12a. This plasmid, named pCriMGET_9-12a (plasmid of synthetic CRISPR-coded RNA target sequence-equipped donor plasmid-mediated gene targeting via Cas9 and Cas12a), comprises the protospacer-adjacent motif sequences of Cas9 and Cas12a at the side of an off-target free synthetic CRISPR-coded RNA target sequence and a multiple cloning site for donor cassette insertion. pCriMGET_9-12a generates a linearized donor cassette in vivo by both CRISPR-Cas9 and CRISPR-Cas12a, which resulted in increased knock-in efficiency in culture cells. This method also achieved > 25% targeted knock-in of long external DNA (> 4 kb) in mice by both CRISPR-Cas9 and CRISPR-Cas12a. The pCriMGET_9-12a system expands the genomic target space for transgene knock-in and provides a versatile, low-cost, and high-performance CRISPR genome editing tool.", "classifications": [ { "id": "JPMJCR2023", "label": "JPMJCR2023", "researcher": "Fumiko Toyoshima", "type": "grant" }, { "id": "Toyoshima", "label": "Group Toyoshima", "parent": "Toyoshima", "type": "group" }, { "id": "Toyoshima", "label": "Team Toyoshima", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Riki", "last_name": "Ishibashi", "name": null }, { "creator_type": "author", "first_name": "Ritsuko", "last_name": "Maki", "name": null }, { "creator_type": "author", "first_name": "Satsuki", "last_name": "Kitano", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Miyachi", "name": null }, { "creator_type": "author", "first_name": "Fumiko", "last_name": "Toyoshima", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41598-022-22639-6" }, "pmcid": { "normalized": "PMC9588054" }, "pmid": { "normalized": "36272994" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "CRISPR-Cas Systems", "descriptor_ui": "D064113", "major_topic": true }, { "descriptor": "DNA", "descriptor_ui": "D004247", "major_topic": false }, { "descriptor": "Endonucleases", "descriptor_ui": "D004720", "major_topic": false }, { "descriptor": "Gene Editing", "descriptor_ui": "D000072669", "major_topic": true }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Plasmids", "descriptor_ui": "D010957", "major_topic": false }, { "descriptor": "RNA", "descriptor_ui": "D012313", "major_topic": false }, { "descriptor": "Transgenes", "descriptor_ui": "D019076", "major_topic": false } ], "publication": { "conference_name": null, "date": "2022 Oct 22", "date_precision": "day", "issue": "1", "normalized_date": "2022-10-22", "pages": "17775", "proceedings_title": null, "publisher": "", "title": "Scientific reports", "volume": "12", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Development of an in vivo cleavable donor plasmid for targeted transgene integration by CRISPR-Cas9 and CRISPR-Cas12a.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Several cross-protective antibodies that recognize a broad range of influenza A virus (IAV) strains are known to have functions in virus elimination such as Fcγ receptor (FcγR)-effector function and neutralizing activity against the head region. Although few studies have used primary cells as effector cells, the FcγR-effector function was evaluated after isolating each cell subset. Herein, we established an original assay system to evaluate purified FI6 IgG-mediated binding to hemagglutinin (HA)-expressing cells by flow cytometry using peripheral blood mononuclear cells from cynomolgus macaques. In addition, we evaluated the FcγR-effector function of IAV vaccine-induced anti-HA antibodies in cynomolgus macaques after administering the split vaccine. We found several cell types, mainly classical monocytes, bound to HA-expressing target cells in an FcγR-dependent manner, that were dominant in the binding of the cell population. Thus, this assay system could facilitate the development of a universal influenza vaccine.", "classifications": [ { "id": "Yamamoto", "label": "Group Yamamoto", "parent": "Toyoshima", "type": "group" }, { "id": "Toyoshima", "label": "Team Toyoshima", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yuji", "last_name": "Masuta", "name": null }, { "creator_type": "author", "first_name": "Shokichi", "last_name": "Takahama", "name": null }, { "creator_type": "author", "first_name": "Takuto", "last_name": "Nogimori", "name": null }, { "creator_type": "author", "first_name": "Saya", "last_name": "Moriyama", "name": null }, { "creator_type": "author", "first_name": "Yoshimasa", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Yamamoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.isci.2022.105085" }, "pmcid": { "normalized": "PMC9486051" }, "pmid": { "normalized": "36147947" } }, "mesh": [], "publication": { "conference_name": null, "date": "2022 Oct 21", "date_precision": "day", "issue": "10", "normalized_date": "2022-10-21", "pages": "105085", "proceedings_title": null, "publisher": "", "title": "iScience", "volume": "25", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Assessment of Fcγ receptor-dependent binding of influenza hemagglutinin vaccine-induced antibodies in a non-human primate model.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "", "classifications": [ { "id": "Yusa", "label": "Group Yusa", "parent": "Eiraku", "type": "group" }, { "id": "Eiraku", "label": "Team Eiraku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Zheng-Shan", "last_name": "Chong", "name": null }, { "creator_type": "author", "first_name": "Shuhei", "last_name": "Ohnishi", "name": null }, { "creator_type": "author", "first_name": "Kosuke", "last_name": "Yusa", "name": null }, { "creator_type": "author", "first_name": "Gavin J.", "last_name": "Wright", "name": null } ], "identifiers": { "doi": { "normalized": "10.1186/s13059-022-02797-6" }, "pmcid": { "normalized": "PMC9585853" }, "pmid": { "normalized": "36271468" } }, "mesh": [], "publication": { "conference_name": null, "date": "2022 Oct 21", "date_precision": "day", "issue": "1", "normalized_date": "2022-10-21", "pages": "224", "proceedings_title": null, "publisher": "", "title": "Genome biology", "volume": "23", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Author Correction: Pooled extracellular receptor-ligand interaction screening using CRISPR activation.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Many organisms living along the coastlines synchronize their reproduction with the lunar cycle. At the time of spring tide, thousands of grass puffers (Takifugu alboplumbeus) aggregate and vigorously tremble their bodies at the water's edge to spawn. To understand the mechanisms underlying this spectacular semilunar beach spawning, we collected the hypothalamus and pituitary from male grass puffers every week for 2 months. RNA sequencing (RNA-seq) analysis identified 125 semilunar genes, including genes crucial for reproduction (e.g., gonadotropin-releasing hormone 1 [gnrh1], luteinizing hormone beta subunit [lhb]) and receptors for pheromone prostaglandin E (PGE). PGE2 is secreted into the seawater during the spawning, and its administration activates olfactory sensory neurons and triggers trembling behavior of surrounding individuals. These results suggest that PGE2 synchronizes lunar-regulated beach-spawning behavior in grass puffers. To further explore the mechanism that regulates the lunar-synchronized transcription of semilunar genes, we searched for semilunar transcription factors. Spatial transcriptomics and multiplex fluorescent in situ hybridization showed co-localization of the semilunar transcription factor CCAAT/enhancer-binding protein delta (cebpd) and gnrh1, and cebpd induced the promoter activity of gnrh1. Taken together, our study demonstrates semilunar genes that mediate lunar-synchronized beach-spawning behavior. VIDEO ABSTRACT.", "classifications": [ { "id": "Sato", "label": "Group Sato", "parent": "Tsuchiya", "type": "group" }, { "id": "Tsuchiya", "label": "Team Tsuchiya", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Junfeng", "last_name": "Chen", "name": null }, { "creator_type": "author", "first_name": "Yuma", "last_name": "Katada", "name": null }, { "creator_type": "author", "first_name": "Kousuke", "last_name": "Okimura", "name": null }, { "creator_type": "author", "first_name": "Taiki", "last_name": "Yamaguchi", "name": null }, { "creator_type": "author", "first_name": "Ying-Jey", "last_name": "Guh", "name": null }, { "creator_type": "author", "first_name": "Tomoya", "last_name": "Nakayama", "name": null }, { "creator_type": "author", "first_name": "Michiyo", "last_name": "Maruyama", "name": null }, { "creator_type": "author", "first_name": "Yuko", "last_name": "Furukawa", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Nakane", "name": null }, { "creator_type": "author", "first_name": "Naoyuki", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Yoshikatsu", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Hironori", "last_name": "Ando", "name": null }, { "creator_type": "author", "first_name": "Asako", "last_name": "Sugimura", "name": null }, { "creator_type": "author", "first_name": "Kazufumi", "last_name": "Tabata", "name": null }, { "creator_type": "author", "first_name": "Ayato", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Yoshimura", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.cub.2022.09.062" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "36306789" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "In Situ Hybridization, Fluorescence", "descriptor_ui": "D017404", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Moon", "descriptor_ui": "D016081", "major_topic": true }, { "descriptor": "Prostaglandins", "descriptor_ui": "D011453", "major_topic": false }, { "descriptor": "Prostaglandins E", "descriptor_ui": "D011458", "major_topic": false }, { "descriptor": "Reproduction", "descriptor_ui": "D012098", "major_topic": false }, { "descriptor": "Takifugu", "descriptor_ui": "D023741", "major_topic": true } ], "publication": { "conference_name": null, "date": "2022 Oct 21", "date_precision": "day", "issue": "", "normalized_date": "2022-10-21", "pages": "S0960-9822(22)01604-9", "proceedings_title": null, "publisher": "", "title": "Current biology : CB", "volume": "", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Prostaglandin E2 synchronizes lunar-regulated beach spawning in grass puffers.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "OBJECTIVE: In recent years, positron emission tomography/magnetic resonance imaging (PET/MRI) has been clinically used as a method to diagnose non-small cell lung cancer (NSCLC). This study aimed to evaluate the concordance of staging and prognostic ability of NSCLC patients using thin-slice computed tomography (CT) and (18)F-fluorodeoxyglucose (FDG) PET/MRI. METHODS: This retrospective study was performed on consecutive NSCLC patients who underwent both diagnostic CT and (18)F-FDG PET/MRI before surgery between November 2015 and May 2019. The cTNM staging yielded from PET/MRI was compared with CT and pathological staging, and concordance was investigated, defining pathological findings as reference. To assess the prognostic value of disease-free survival (DFS) and overall survival (OS), we dichotomized the typical prognostic factors and TNM classification staging (Stage I vs. Stage II or higher). Kaplan-Meier curves derived by the log-rank test were generated, and univariate and multivariate analyses were performed to identify the factors associated with DFS and OS. RESULTS: A total of 82 subjects were included; PET/MRI staging was more consistent (59 of 82) with pathological staging than with CT staging. There was a total of 21 cases of CT and 11 cases of PET/MRI that were judged as cStage I, but were actually pStage II or pStage III. CT tended to judge pN1 or pN2 as cN0 compared to PET/MRI. There was a significant difference between NSCLC patients with Stage I and Stage II or higher by PET/MRI staging as well as prognosis prediction of DFS by pathological staging (P < 0.001). In univariate analysis, PET/MRI, CT, and pathological staging (Stage I or lower vs. Stage II or higher) all showed significant differences as prognostic factors of recurrence or metastases. In multivariate analysis, pathological staging was the only independent factor for recurrence (P = 0.009), and preoperative PET/MRI staging was a predictor of patient survival (P = 0.013). CONCLUSIONS: In NSCLC, pathologic staging was better at predicting recurrence, and preoperative PET/MRI staging was better at predicting survival. Preoperative staging by PET/MRI was superior to CT in diagnosing hilar and mediastinal lymph-node metastases, which contributed to the high concordance with pathologic staging.", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Akiko", "last_name": "Kajiyama", "name": null }, { "creator_type": "author", "first_name": "Kimiteru", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Hirokazu", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Sunao", "last_name": "Mizumura", "name": null }, { "creator_type": "author", "first_name": "Shun-Ichi", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Gomi", "name": null }, { "creator_type": "author", "first_name": "Masahiko", "last_name": "Kusumoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/s12149-022-01795-9" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "36264439" } }, "mesh": [ { "descriptor": "Carcinoma, Non-Small-Cell Lung", "descriptor_ui": "D002289", "major_topic": true }, { "descriptor": "Fluorodeoxyglucose F18", "descriptor_ui": "D019788", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Lung Neoplasms", "descriptor_ui": "D008175", "major_topic": true }, { "descriptor": "Magnetic Resonance Imaging", "descriptor_ui": "D008279", "major_topic": false }, { "descriptor": "Neoplasm Staging", "descriptor_ui": "D009367", "major_topic": false }, { "descriptor": "Positron-Emission Tomography", "descriptor_ui": "D049268", "major_topic": false }, { "descriptor": "Prognosis", "descriptor_ui": "D011379", "major_topic": false }, { "descriptor": "Radiopharmaceuticals", "descriptor_ui": "D019275", "major_topic": false }, { "descriptor": "Retrospective Studies", "descriptor_ui": "D012189", "major_topic": false } ], "publication": { "conference_name": null, "date": "2022 Oct 20", "date_precision": "day", "issue": "", "normalized_date": "2022-10-20", "pages": "", "proceedings_title": null, "publisher": "", "title": "Annals of nuclear medicine", "volume": "", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Consistency and prognostic value of preoperative staging and postoperative pathological staging using (18)F-FDG PET/MRI in patients with non-small cell lung cancer.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: The 8th edition of the TNM stage classification of lung cancer was developed based on an evaluation of the 5-year prognosis using an international database. Since recurrence after 5 years postoperatively is known to develop, the applicability of the stage classification beyond 5 years after treatment needs to be evaluated. PATIENTS AND METHODS: Postoperative prognosis and prognostic indicators were analyzed using data for 648 patients of pathological stage IA adenocarcinoma, who underwent complete resection between 2007 and 2012. RESULTS: The median age was 66 years (interquartile range 60-73 years), and the median follow-up duration was 100 months (interquartile range 70-116 months). Overall survival probabilities for pathological stage IA1, IA2, and IA3 patients were 100%, 96.3%, and 91.5% at 5 postoperative years, and 94.2%, 89.8%, and 83.5% at 10 postoperative years, respectively (IA1 vs IA2: p = 0.05; IA2 vs IA3: p = 0.05). Multivariate analysis for overall survival of patients who survived without recurrence for 5 postoperative years revealed that age (hazard ratio 3.21, p = 0.02) was the only factor that was significantly associated with long-term survival. Stage classification (IA1, IA2, or IA3) was not an associated factor. The incidence of secondary primary lung cancer continued to increase, resulting in an estimated probability of 8.6% at 10 postoperative years. CONCLUSIONS: For patients who survived without recurrence for 5 postoperative years, age, not stage classification, was associated with survival thereafter. The long-term follow-up strategy does not need to be modified according to the stage classification, and screening for secondary primary lung cancer should be considered.", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Masaya", "last_name": "Yotsukura", "name": null }, { "creator_type": "author", "first_name": "Yuji", "last_name": "Muraoka", "name": null }, { "creator_type": "author", "first_name": "Yukihiro", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Kazuo", "last_name": "Nakagawa", "name": null }, { "creator_type": "author", "first_name": "Kouya", "last_name": "Shiraishi", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Kohno", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null }, { "creator_type": "author", "first_name": "Shun-Ichi", "last_name": "Watanabe", "name": null } ], "identifiers": { "doi": { "normalized": "10.1245/s10434-022-12621-x" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "36260144" } }, "mesh": [ { "descriptor": "Adenocarcinoma", "descriptor_ui": "D000230", "major_topic": true }, { "descriptor": "Adenocarcinoma of Lung", "descriptor_ui": "D000077192", "major_topic": true }, { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Lung Neoplasms", "descriptor_ui": "D008175", "major_topic": true }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Neoplasm Staging", "descriptor_ui": "D009367", "major_topic": false }, { "descriptor": "Prognosis", "descriptor_ui": "D011379", "major_topic": false }, { "descriptor": "Retrospective Studies", "descriptor_ui": "D012189", "major_topic": false } ], "publication": { "conference_name": null, "date": "2022 Oct 19", "date_precision": "day", "issue": "", "normalized_date": "2022-10-19", "pages": "", "proceedings_title": null, "publisher": "", "title": "Annals of surgical oncology", "volume": "", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Long-Term Prognosis and Prognostic Indicators of Stage IA Lung Adenocarcinoma.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The PI3K pathway is commonly activated in breast cancer, with PI3K-AKT pathway inhibitors used clinically. However, mechanisms that limit or enhance the therapeutic effects of PI3K-AKT inhibitors are poorly understood at a genome-wide level. Parallel CRISPR screens in 3 PTEN-null breast cancer cell lines identified genes mediating resistance to capivasertib (AKT inhibitor) and AZD8186 (PI3Kbeta inhibitor). The dominant mechanism causing resistance is reactivated PI3K-AKT-mTOR signalling, but not other canonical signalling pathways. Deletion of TSC1/2 conferred resistance to PI3Kbetai and AKTi through mTORC1. However, deletion of PIK3R2 and INPPL1 drove specific PI3Kbetai resistance through AKT. Conversely deletion of PIK3CA, ERBB2, ERBB3 increased PI3Kbetai sensitivity while modulation of RRAGC, LAMTOR1, LAMTOR4 increased AKTi sensitivity. Significantly, we found that Mcl-1 loss enhanced response through rapid apoptosis induction with AKTi and PI3Kbetai in both sensitive and drug resistant TSC1/2 null cells. The combination effect was BAK but not BAX dependent. The Mcl-1i + PI3Kbeta/AKTi combination was effective across a panel of breast cancer cell lines with PIK3CA and PTEN mutations, and delivered increased anti-tumor benefit in vivo. This study demonstrates that different resistance drivers to PI3Kbetai and AKTi converge to reactivate PI3K-AKT or mTOR signalling and combined inhibition of Mcl-1 and PI3K-AKT has potential as a treatment strategy for PI3Kbetai/AKTi sensitive and resistant breast tumours.", "classifications": [ { "id": "Yusa", "label": "Group Yusa", "parent": "Eiraku", "type": "group" }, { "id": "Eiraku", "label": "Team Eiraku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Shanade", "last_name": "Dunn", "name": null }, { "creator_type": "author", "first_name": "Cath", "last_name": "Eberlein", "name": null }, { "creator_type": "author", "first_name": "Jason", "last_name": "Yu", "name": null }, { "creator_type": "author", "first_name": "Albert", "last_name": "Gris-Oliver", "name": null }, { "creator_type": "author", "first_name": "Swee Hoe", "last_name": "Ong", "name": null }, { "creator_type": "author", "first_name": "Urs", "last_name": "Yelland", "name": null }, { "creator_type": "author", "first_name": "Natalie", "last_name": "Cureton", "name": null }, { "creator_type": "author", "first_name": "Anna", "last_name": "Staniszewska", "name": null }, { "creator_type": "author", "first_name": "Robert", "last_name": "McEwen", "name": null }, { "creator_type": "author", "first_name": "Millie", "last_name": "Fox", "name": null }, { "creator_type": "author", "first_name": "James", "last_name": "Pilling", "name": null }, { "creator_type": "author", "first_name": "Philip", "last_name": "Hopcroft", "name": null }, { "creator_type": "author", "first_name": "Elizabeth A.", "last_name": "Coker", "name": null }, { "creator_type": "author", "first_name": "Patricia", "last_name": "Jaaks", "name": null }, { "creator_type": "author", "first_name": "Mathew J.", "last_name": "Garnett", "name": null }, { "creator_type": "author", "first_name": "Beverley", "last_name": "Isherwood", "name": null }, { "creator_type": "author", "first_name": "Violeta", "last_name": "Serra", "name": null }, { "creator_type": "author", "first_name": "Barry R.", "last_name": "Davies", "name": null }, { "creator_type": "author", "first_name": "Simon T.", "last_name": "Barry", "name": null }, { "creator_type": "author", "first_name": "James T.", "last_name": "Lynch", "name": null }, { "creator_type": "author", "first_name": "Kosuke", "last_name": "Yusa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41388-022-02482-9" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "36241868" } }, "mesh": [ { "descriptor": "Antineoplastic Agents", "descriptor_ui": "D000970", "major_topic": true }, { "descriptor": "Breast Neoplasms", "descriptor_ui": "D001943", "major_topic": true }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Class I Phosphatidylinositol 3-Kinases", "descriptor_ui": "D058534", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Guanine Nucleotide Exchange Factors", "descriptor_ui": "D020662", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mechanistic Target of Rapamycin Complex 1", "descriptor_ui": "D000076222", "major_topic": false }, { "descriptor": "Phosphatidylinositol 3-Kinases", "descriptor_ui": "D019869", "major_topic": false }, { "descriptor": "Phosphoinositide-3 Kinase Inhibitors", "descriptor_ui": "D000081082", "major_topic": false }, { "descriptor": "Protein Kinase Inhibitors", "descriptor_ui": "D047428", "major_topic": false }, { "descriptor": "Proto-Oncogene Proteins c-akt", "descriptor_ui": "D051057", "major_topic": false }, { "descriptor": "PTEN Phosphohydrolase", "descriptor_ui": "D051059", "major_topic": false }, { "descriptor": "TOR Serine-Threonine Kinases", "descriptor_ui": "D058570", "major_topic": false } ], "publication": { "conference_name": null, "date": "2022 Oct 14", "date_precision": "day", "issue": "", "normalized_date": "2022-10-14", "pages": "", "proceedings_title": null, "publisher": "", "title": "Oncogene", "volume": "", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "AKT-mTORC1 reactivation is the dominant resistance driver for PI3Kbeta/AKT inhibitors in PTEN-null breast cancer and can be overcome by combining with Mcl-1 inhibitors.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The measurement of cytoskeletal features can provide valuable insights into cell biology. In recent years, digital image analysis of cytoskeletal features has become an important research tool for quantitative evaluation of cytoskeleton organization. In this study, we examined the utility of a supervised machine learning approach with digital image analysis to distinguish different cellular organizational patterns. We focused on the jigsaw puzzle-shaped pavement cells of Arabidopsis thaliana. Measurements of three features of cortical microtubules in these cells (parallelness, density, and the coefficient of variation of the intensity distribution of fluorescently labeled cytoskeletons [as an indicator of microtubule bundling]) were obtained from microscopic images. A random forest machine learning model was then used with these images to differentiate mutant and wild type, and Taxol-treated and control cells. Using these three metrics, we were able to distinguish wild type from bpp125 triple mutant cells, with approximately 80% accuracy; classification accuracy was 88% for control and Taxol-treated cells. Different features contributed most to the classification, namely, coefficient of variation for the wild-type/mutant cells and parallelness for the Taxol-treated/control cells. The random forest method used enabled quantitative evaluation of the contribution of features to the classification, and partial dependence plots showed the relationships between metric values and classification accuracy. While further improvements to the method are needed, our small-scale analysis shows the potential for this approach in large-scale screening analyses.", "classifications": [ { "id": "JPMJCR2121", "label": "JPMJCR2121", "researcher": "Minako Ueda", "type": "grant" }, { "id": "Higaki", "label": "Group Higaki", "parent": "Ueda", "type": "group" }, { "id": "Ueda", "label": "Group Ueda", "parent": "Ueda", "type": "group" }, { "id": "Ueda", "label": "Team Ueda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Daichi", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Kae", "last_name": "Akita", "name": null }, { "creator_type": "author", "first_name": "Takumi", "last_name": "Higaki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/s00709-022-01813-7" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "36219259" } }, "mesh": [ { "descriptor": "Arabidopsis", "descriptor_ui": "D017360", "major_topic": true }, { "descriptor": "Arabidopsis Proteins", "descriptor_ui": "D029681", "major_topic": true }, { "descriptor": "Cotyledon", "descriptor_ui": "D018548", "major_topic": false }, { "descriptor": "Machine Learning", "descriptor_ui": "D000069550", "major_topic": false }, { "descriptor": "Microtubules", "descriptor_ui": "D008870", "major_topic": false }, { "descriptor": "Paclitaxel", "descriptor_ui": "D017239", "major_topic": false } ], "publication": { "conference_name": null, "date": "2022 Oct 11", "date_precision": "day", "issue": "", "normalized_date": "2022-10-11", "pages": "", "proceedings_title": null, "publisher": "", "title": "Protoplasma", "volume": "", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Machine learning and feature analysis of the cortical microtubule organization of Arabidopsis cotyledon pavement cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Curcumin (aglycone curcumin) has antitumor properties in a variety of malignancies via the alteration of multiple cancer-related biological pathways; however, its clinical application has been hampered due to its poor bioavailability. To overcome this limitation, we have developed a synthesized curcumin beta-D-glucuronide sodium salt (TBP1901), a prodrug form of aglycone curcumin. In this study, we aimed to clarify the pharmacologic characteristics of TBP1901. In beta-glucuronidase (GUSB)-proficient mice, both curcumin beta-D-glucuronide and its active metabolite, aglycone curcumin, were detected in the blood after TBP1901 injection, whereas only curcumin beta-D-glucuronide was detected in GUSB-impaired mice, suggesting that GUSB plays a pivotal role in the conversion of TBP1901 into aglycone curcumin in vivo. TBP1901 itself had minimal antitumor effects in vitro, whereas it demonstrated significant antitumor effects in vivo. Genome-wide clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 screen disclosed the genes associated with NF-kappaB signaling pathway and mitochondria were among the highest hit. In vitro, aglycone curcumin inhibited NF-kappa B signaling pathways whereas it caused production of reactive oxygen species (ROS). ROS scavenger, N-acetyl-L-cysteine, partially reversed antitumor effects of aglycone curcumin. In summary, TBP1901 can exert antitumor effects as a prodrug of aglycone curcumin through GUSB-dependent activation.", "classifications": [ { "id": "Yusa", "label": "Group Yusa", "parent": "Eiraku", "type": "group" }, { "id": "Eiraku", "label": "Team Eiraku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Tomoyuki", "last_name": "Abe", "name": null }, { "creator_type": "author", "first_name": "Yoshihito", "last_name": "Horisawa", "name": null }, { "creator_type": "author", "first_name": "Osamu", "last_name": "Kikuchi", "name": null }, { "creator_type": "author", "first_name": "Hitomi", "last_name": "Ozawa-Umeta", "name": null }, { "creator_type": "author", "first_name": "Atsuhiro", "last_name": "Kishimoto", "name": null }, { "creator_type": "author", "first_name": "Yasuhiro", "last_name": "Katsuura", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Imaizumi", "name": null }, { "creator_type": "author", "first_name": "Tadashi", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Kotaro", "last_name": "Shirakawa", "name": null }, { "creator_type": "author", "first_name": "Akifumi", "last_name": "Takaori-Kondo", "name": null }, { "creator_type": "author", "first_name": "Kosuke", "last_name": "Yusa", "name": null }, { "creator_type": "author", "first_name": "Tadashi", "last_name": "Asakura", "name": null }, { "creator_type": "author", "first_name": "Hideaki", "last_name": "Kakeya", "name": null }, { "creator_type": "author", "first_name": "Masashi", "last_name": "Kanai", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.ejphar.2022.175321" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "36228744" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "CRISPR-Cas Systems", "descriptor_ui": "D064113", "major_topic": false }, { "descriptor": "Curcumin", "descriptor_ui": "D003474", "major_topic": true }, { "descriptor": "Glucuronidase", "descriptor_ui": "D005966", "major_topic": false }, { "descriptor": "Glucuronides", "descriptor_ui": "D020719", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "NF-kappa B", "descriptor_ui": "D016328", "major_topic": false }, { "descriptor": "Prodrugs", "descriptor_ui": "D011355", "major_topic": true }, { "descriptor": "Reactive Oxygen Species", "descriptor_ui": "D017382", "major_topic": false } ], "publication": { "conference_name": null, "date": "2022 Oct 10", "date_precision": "day", "issue": "", "normalized_date": "2022-10-10", "pages": "175321", "proceedings_title": null, "publisher": "", "title": "European journal of pharmacology", "volume": "935", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Pharmacologic characterization of TBP1901, a prodrug form of aglycone curcumin, and CRISPR-Cas9 screen for therapeutic targets of aglycone curcumin.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Upon the initiation of collective cell migration, the cells at the free edge are specified as leader cells; however, the mechanism underlying the leader cell specification remains elusive. Here, we show that lamellipodial extension after the release from mechanical confinement causes sustained extracellular signal-regulated kinase (ERK) activation and underlies the leader cell specification. Live-imaging of Madin-Darby canine kidney (MDCK) cells and mouse epidermis through the use of Forster resonance energy transfer (FRET)-based biosensors showed that leader cells exhibit sustained ERK activation in a hepatocyte growth factor (HGF)-dependent manner. Meanwhile, follower cells exhibit oscillatory ERK activation waves in an epidermal growth factor (EGF) signaling-dependent manner. Lamellipodial extension at the free edge increases the cellular sensitivity to HGF. The HGF-dependent ERK activation, in turn, promotes lamellipodial extension, thereby forming a positive feedback loop between cell extension and ERK activation and specifying the cells at the free edge as the leader cells. Our findings show that the integration of physical and biochemical cues underlies the leader cell specification during collective cell migration.", "classifications": [], "creators": [ { "creator_type": "author", "first_name": "Naoya", "last_name": "Hino", "name": null }, { "creator_type": "author", "first_name": "Kimiya", "last_name": "Matsuda", "name": null }, { "creator_type": "author", "first_name": "Yuya", "last_name": "Jikko", "name": null }, { "creator_type": "author", "first_name": "Gembu", "last_name": "Maryu", "name": null }, { "creator_type": "author", "first_name": "Katsuya", "last_name": "Sakai", "name": null }, { "creator_type": "author", "first_name": "Ryu", "last_name": "Imamura", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Tsukiji", "name": null }, { "creator_type": "author", "first_name": "Kazuhiro", "last_name": "Aoki", "name": null }, { "creator_type": "author", "first_name": "Kenta", "last_name": "Terai", "name": null }, { "creator_type": "author", "first_name": "Tsuyoshi", "last_name": "Hirashima", "name": null }, { "creator_type": "author", "first_name": "Xavier", "last_name": "Trepat", "name": null }, { "creator_type": "author", "first_name": "Michiyuki", "last_name": "Matsuda", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.devcel.2022.09.003" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "36174555" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Movement", "descriptor_ui": "D002465", "major_topic": false }, { "descriptor": "Dogs", "descriptor_ui": "D004285", "major_topic": false }, { "descriptor": "Epidermal Growth Factor", "descriptor_ui": "D004815", "major_topic": false }, { "descriptor": "Extracellular Signal-Regulated MAP Kinases", "descriptor_ui": "D048049", "major_topic": true }, { "descriptor": "Feedback", "descriptor_ui": "D005246", "major_topic": false }, { "descriptor": "Hepatocyte Growth Factor", "descriptor_ui": "D017228", "major_topic": true }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false } ], "publication": { "conference_name": null, "date": "2022 Oct 10", "date_precision": "day", "issue": "19", "normalized_date": "2022-10-10", "pages": "2290-2304.e7", "proceedings_title": null, "publisher": "", "title": "Developmental cell", "volume": "57", "year": 2022 }, "ssbd": { "database": [], "repository": [ "ssbd-repos-000248" ] }, "title": "A feedback loop between lamellipodial extension and HGF-ERK signaling specifies leader cells during collective cell migration.", "url": "https://www.sciencedirect.com/science/article/pii/S1534580722006335?via%3Dihub", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Retinoblastoma (RB) is the most common intraocular pediatric cancer. Nearly all cases of RB are associated with mutations compromising the function of the RB1 tumor suppressor gene. We previously demonstrated that PRELP is widely downregulated in various cancers and our in vivo and in vitro analysis revealed PRELP as a novel tumor suppressor and regulator of EMT. In addition, PRELP is located at chromosome 1q31.1, around a region hypothesized to be associated with the initiation of malignancy in RB. Therefore, in this study, we investigated the role of PRELP in RB through in vitro analysis and next-generation sequencing. Immunostaining revealed that PRELP is expressed in Muller glial cells in the retina. mRNA expression profiling of PRELP(-/-) mouse retina and PRELP-treated RB cells found that PRELP contributes to RB progression via regulation of the cancer microenvironment, in which loss of PRELP reduces cell-cell adhesion and facilitates EMT. Our observations suggest that PRELP may have potential as a new strategy for RB treatment.", "classifications": [ { "id": "Hamamoto", "label": "Group Hamamoto", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Jack", "last_name": "Hopkins", "name": null }, { "creator_type": "author", "first_name": "Ken", "last_name": "Asada", "name": null }, { "creator_type": "author", "first_name": "Alex", "last_name": "Leung", "name": null }, { "creator_type": "author", "first_name": "Vasiliki", "last_name": "Papadaki", "name": null }, { "creator_type": "author", "first_name": "Hongorzul", "last_name": "Davaapil", "name": null }, { "creator_type": "author", "first_name": "Matthew", "last_name": "Morrison", "name": null }, { "creator_type": "author", "first_name": "Tomoko", "last_name": "Orita", "name": null }, { "creator_type": "author", "first_name": "Ryohei", "last_name": "Sekido", "name": null }, { "creator_type": "author", "first_name": "Hirofumi", "last_name": "Kosuge", "name": null }, { "creator_type": "author", "first_name": "M. Ashwin", "last_name": "Reddy", "name": null }, { "creator_type": "author", "first_name": "Kazuhiro", "last_name": "Kimura", "name": null }, { "creator_type": "author", "first_name": "Akihisa", "last_name": "Mitani", "name": null }, { "creator_type": "author", "first_name": "Kouhei", "last_name": "Tsumoto", "name": null }, { "creator_type": "author", "first_name": "Ryuji", "last_name": "Hamamoto", "name": null }, { "creator_type": "author", "first_name": "Mandeep S.", "last_name": "Sagoo", "name": null }, { "creator_type": "author", "first_name": "Shin-Ichi", "last_name": "Ohnuma", "name": null } ], "identifiers": { "doi": { "normalized": "10.3390/cancers14194926" }, "pmcid": { "normalized": "PMC9563430" }, "pmid": { "normalized": "36230849" } }, "mesh": [], "publication": { "conference_name": null, "date": "2022 Oct 8", "date_precision": "day", "issue": "19", "normalized_date": "2022-10-08", "pages": "4926", "proceedings_title": null, "publisher": "", "title": "Cancers", "volume": "14", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "PRELP Regulates Cell-Cell Adhesion and EMT and Inhibits Retinoblastoma Progression.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "N-cadherin (NCad) is a classical cadherin that mediates cell-cell interactions in a Ca(2+)-dependent manner. NCad participates in various biological processes, from ontogenesis to higher brain functions, though the visualization of NCad interactions in living cells remains limited. Here, we present intensiometric NCad interaction indicators, named INCIDERs, that utilize dimerization-dependent fluorescent proteins. INCIDERs successfully visualize reversible NCad interactions across cells. Compared to FRET-based indicators, INCIDERs have a ~70-fold higher signal contrast, enabling clear identification of NCad interactions. In primary neuronal cells, NCad interactions are visualized between closely apposed processes. Furthermore, visualization of NCad interaction at cell adhesion sites in dense cell populations is achieved by two-photon microscopy. INCIDERs are useful tools in the spatiotemporal investigation of NCad interactions across cells; future research should evaluate the potential of INCIDERs in mapping complex three-dimensional architectures in multi-cellular systems.", "classifications": [ { "id": "Eiraku", "label": "Group Eiraku", "parent": "Eiraku", "type": "group" }, { "id": "Eiraku", "label": "Team Eiraku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Takashi", "last_name": "Kanadome", "name": null }, { "creator_type": "author", "first_name": "Kanehiro", "last_name": "Hayashi", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Seto", "name": null }, { "creator_type": "author", "first_name": "Mototsugu", "last_name": "Eiraku", "name": null }, { "creator_type": "author", "first_name": "Kazunori", "last_name": "Nakajima", "name": null }, { "creator_type": "author", "first_name": "Takeharu", "last_name": "Nagai", "name": null }, { "creator_type": "author", "first_name": "Tomoki", "last_name": "Matsuda", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s42003-022-04023-2" }, "pmcid": { "normalized": "PMC9546846" }, "pmid": { "normalized": "36207396" } }, "mesh": [ { "descriptor": "Cadherins", "descriptor_ui": "D015820", "major_topic": true }, { "descriptor": "Cell Adhesion", "descriptor_ui": "D002448", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": true } ], "publication": { "conference_name": null, "date": "2022 Oct 7", "date_precision": "day", "issue": "1", "normalized_date": "2022-10-07", "pages": "1065", "proceedings_title": null, "publisher": "", "title": "Communications biology", "volume": "5", "year": 2022 }, "ssbd": { "database": [ "ssbd-database-000283" ], "repository": [ "ssbd-repos-000283" ] }, "title": "Development of intensiometric indicators for visualizing N-cadherin interaction across cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The induction mechanism of heme oxygenase-1 (HO-1) by heat shock (HS) is still unknown. Here, we discovered that HS activates the HO-1 expression in a mouse hepatoma cell line (Hepa 1-6). Knockdown experiments showed that the HS-induced HO-1 expression was dependent on HS factor 1 (HSF1). A chromatin immunoprecipitation (ChIP) assay demonstrated that the HS-activated HSF1 bound to the HS elements (HSEs) in the upstream enhancer 1 region (E1). Unexpectedly, HS also facilitates the BTB and CNC homology 1 (BACH1) binding to the Maf recognition elements (MAREs) in E1. We examined the effects of a catalytically inactive CRISPR-associated 9 nucleases (dCas9) with short guide RNAs (sgRNAs), and demonstrated that the HSF1 binding to HSEs in E1 was indispensable for the HS-induced HO-1 expression. Heme treatment (HA) dissociates BACH1 from MAREs and facilitated the binding of nuclear factor-erythroid-2-related factor 2 (NRF2) to MAREs. Following treatment with both HS and HA, the HO-1 induction and the HSF1 binding to HSEs in E1 were most notably observed. These results indicate that the HS-induced HO-1 expression is dependent on the HSF1 binding to HSEs in E1, although modulated by the BACH1 and NRF2 binding to MAREs within the same E1.", "classifications": [ { "id": "Miyamoto", "label": "Group Miyamoto", "parent": "Wakamoto", "type": "group" }, { "id": "Wakamoto", "label": "Team Wakamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Sachiye", "last_name": "Inouye", "name": null }, { "creator_type": "author", "first_name": "Takanori", "last_name": "Kubo", "name": null }, { "creator_type": "author", "first_name": "Takafumi", "last_name": "Miyamoto", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Iyoda", "name": null }, { "creator_type": "author", "first_name": "Naoyuki", "last_name": "Okita", "name": null }, { "creator_type": "author", "first_name": "Reiko", "last_name": "Akagi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/gtc.12986" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "36203316" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Basic-Leucine Zipper Transcription Factors", "descriptor_ui": "D050976", "major_topic": false }, { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "Heat Shock Transcription Factors", "descriptor_ui": "D000076249", "major_topic": false }, { "descriptor": "Heat-Shock Response", "descriptor_ui": "D018869", "major_topic": true }, { "descriptor": "Heme Oxygenase-1", "descriptor_ui": "D051547", "major_topic": true }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false } ], "publication": { "conference_name": null, "date": "2022 Oct 6", "date_precision": "day", "issue": "", "normalized_date": "2022-10-06", "pages": "", "proceedings_title": null, "publisher": "", "title": "Genes to cells : devoted to molecular & cellular mechanisms", "volume": "", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Heat shock-induced heme oxygenase-1 expression in a mouse hepatoma cell line is dependent on HSF1 and modified by NRF2 and BACH1.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Nucleic acid-based adjuvants such as CpG oligonucleotides (CpG ODNs) and poly(I:C) are potential vaccine adjuvants for infectious diseases and cancers. However, the mechanism by which their cell surface receptors promote their uptake into dendritic cells (DCs) and shuttle them to intracellular Toll-like receptors remains to be further investigated. Here, we demonstrated a role for nucleolin, a multifunctional DNA- and RNA-binding protein and a major constituent of the nucleolus, as one of the cell-surface receptors for nucleic acid-based adjuvants. Nucleolin on mouse DC surface bound directly to A-type CpG ODN, B-type CpG ODN, and poly(I:C) and promoted their internalization into cells following DC maturation in vitro. In human DCs, nucleolin also contributed to the binding and internalization of both types of CpG ODNs and subsequent cytokine production. Furthermore, nucleolin played a crucial role in cytokine production and activating antigen-specific antibodies and T cell responses induced by B-type CpG ODN in vivo in mice. Our findings provide valuable information that can help improve the efficacy and safety of these adjuvants.", "classifications": [ { "id": "Yamamoto", "label": "Group Yamamoto", "parent": "Toyoshima", "type": "group" }, { "id": "Toyoshima", "label": "Team Toyoshima", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Satoki", "last_name": "Kitagawa", "name": null }, { "creator_type": "author", "first_name": "Teppei", "last_name": "Matsuda", "name": null }, { "creator_type": "author", "first_name": "Ayaka", "last_name": "Washizaki", "name": null }, { "creator_type": "author", "first_name": "Hirotomo", "last_name": "Murakami", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Yasuo", "last_name": "Yoshioka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41541-022-00541-6" }, "pmcid": { "normalized": "PMC9537314" }, "pmid": { "normalized": "36202858" } }, "mesh": [], "publication": { "conference_name": null, "date": "2022 Oct 6", "date_precision": "day", "issue": "1", "normalized_date": "2022-10-06", "pages": "115", "proceedings_title": null, "publisher": "", "title": "NPJ vaccines", "volume": "7", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Elucidation of the role of nucleolin as a cell surface receptor for nucleic acid-based adjuvants.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Primary pancreatic lymphoma is a rare pancreatic malignancy, reportedly accounting for only 0.2-0.7% of all primary pancreatic tumors. Primary pancreatic lymphoma is often difficult to distinguish from other diseases, such as acute pancreatitis. We herein report the autopsy of a patient with primary pancreatic lymphoma with imaging findings resembling those of severe acute pancreatitis, with a focus on the gross and histological features.", "classifications": [ { "id": "Tanaka", "label": "Group Tanaka", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yoshinori", "last_name": "Harada", "name": null }, { "creator_type": "author", "first_name": "Yoshio", "last_name": "Sogame", "name": null }, { "creator_type": "author", "first_name": "Ryuta", "last_name": "Nakao", "name": null }, { "creator_type": "author", "first_name": "Takehiro", "last_name": "Ogata", "name": null }, { "creator_type": "author", "first_name": "Hiroaki", "last_name": "Yasuda", "name": null }, { "creator_type": "author", "first_name": "Junichi", "last_name": "Sakagami", "name": null }, { "creator_type": "author", "first_name": "Yoshito", "last_name": "Itoh", "name": null }, { "creator_type": "author", "first_name": "Hideo", "last_name": "Tanaka", "name": null } ], "identifiers": { "doi": { "normalized": "10.2169/internalmedicine.0757-22" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "36198606" } }, "mesh": [ { "descriptor": "Acute Disease", "descriptor_ui": "D000208", "major_topic": false }, { "descriptor": "Autopsy", "descriptor_ui": "D001344", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Lymphoma", "descriptor_ui": "D008223", "major_topic": true }, { "descriptor": "Pancreatic Neoplasms", "descriptor_ui": "D010190", "major_topic": true }, { "descriptor": "Pancreatitis", "descriptor_ui": "D010195", "major_topic": true } ], "publication": { "conference_name": null, "date": "2022 Oct 5", "date_precision": "day", "issue": "", "normalized_date": "2022-10-05", "pages": "", "proceedings_title": null, "publisher": "", "title": "Internal medicine (Tokyo, Japan)", "volume": "", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Autopsy of a Patient with Primary Pancreatic Lymphoma with Findings Resembling Severe Acute Pancreatitis.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: There are limited studies on the results of comprehensive genomic profiling testing for pancreatic cancer tissue specimens by endoscopic ultrasound-guided tissue acquisition (EUS-TA). This study aimed to evaluate the proportion of specimens obtained by EUS-TA using a 19-gauge (G) fine-needle biopsy (FNB) needle for unresectable pancreatic cancer (UR-PC) that met the OncoGuide() NCC Oncopanel System (NOP) analysis suitability criteria. METHODS: In this single-arm, prospective, phase II study, EUS-TA was performed using a 19G FNB biopsy needle in patients with suspected UR-PC based on a contrast-enhanced computed tomography scan. The primary endpoint was the proportion of patients who met the NOP analysis suitability criteria, with a threshold, expected value, alpha-error, and power of 40%, 70%, 0.025, and 0.9, respectively, and the planned number of enrolled patients was 33. The NOP analysis suitability criteria were defined as tumor cell content >/= 20% and tissue size >/= 4 mm(2). RESULTS: Thirty-three patients were enrolled. The procedural success rate was 100%, and the cytodiagnosis of class V was observed in all patients. The proportion of patients meeting the NOP analysis suitability criteria was 63.6% (95% CI 47.22-80.05), which satisfied the predefined criteria to be considered valid. Adverse events occurred in 9.0% of the patients. CONCLUSIONS: The proportion of patients with UR-PC who met the NOP analysis suitability criteria for EUS-TA using a 19G FNB needle was effective for achieving the primary endpoint, making it a valid test method. Adverse events occurred at a higher rate than that previously reported.", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yuya", "last_name": "Hisada", "name": null }, { "creator_type": "author", "first_name": "Susumu", "last_name": "Hijioka", "name": null }, { "creator_type": "author", "first_name": "Go", "last_name": "Ikeda", "name": null }, { "creator_type": "author", "first_name": "Kosuke", "last_name": "Maehara", "name": null }, { "creator_type": "author", "first_name": "Taiki", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Hidetoshi", "last_name": "Kitamura", "name": null }, { "creator_type": "author", "first_name": "Shota", "last_name": "Harai", "name": null }, { "creator_type": "author", "first_name": "Motohiro", "last_name": "Yoshinari", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Kawasaki", "name": null }, { "creator_type": "author", "first_name": "Yumi", "last_name": "Murashima", "name": null }, { "creator_type": "author", "first_name": "Takehiko", "last_name": "Koga", "name": null }, { "creator_type": "author", "first_name": "Kotaro", "last_name": "Takeshita", "name": null }, { "creator_type": "author", "first_name": "Yuta", "last_name": "Maruki", "name": null }, { "creator_type": "author", "first_name": "Akihiro", "last_name": "Ohba", "name": null }, { "creator_type": "author", "first_name": "Yoshikuni", "last_name": "Nagashio", "name": null }, { "creator_type": "author", "first_name": "Shunsuke", "last_name": "Kondo", "name": null }, { "creator_type": "author", "first_name": "Chigusa", "last_name": "Morizane", "name": null }, { "creator_type": "author", "first_name": "Hideki", "last_name": "Ueno", "name": null }, { "creator_type": "author", "first_name": "Yutaka", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null }, { "creator_type": "author", "first_name": "Takuji", "last_name": "Okusaka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/s00535-022-01926-z" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "36190682" } }, "mesh": [ { "descriptor": "Endoscopic Ultrasound-Guided Fine Needle Aspiration", "descriptor_ui": "D061765", "major_topic": true }, { "descriptor": "Endosonography", "descriptor_ui": "D019160", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Pancreatic Neoplasms", "descriptor_ui": "D010190", "major_topic": true }, { "descriptor": "Prospective Studies", "descriptor_ui": "D011446", "major_topic": false } ], "publication": { "conference_name": null, "date": "2022 Oct 3", "date_precision": "day", "issue": "", "normalized_date": "2022-10-03", "pages": "", "proceedings_title": null, "publisher": "", "title": "Journal of gastroenterology", "volume": "", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Proportion of unresectable pancreatic cancer specimens obtained by endoscopic ultrasound-guided tissue acquisition meeting the OncoGuide NCC Oncopanel System analysis suitability criteria: a single-arm, phase II clinical trial.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Hibernoma is an uncommon benign tumor of brown fat cells that consistently expresses uncoupling protein 1 (UCP1). Herein, we clinicopathologically characterized 16 liposarcomas, for which histology, at least focally, closely resembled that of hibernoma, including sheets of brown fat-like, finely multivacuolated-to-eosinophilic tumor cells with no or minimal nuclear atypia. The cohort consisted of 4 well-differentiated liposarcomas (WDLSs), 6 dedifferentiated liposarcomas with a concomitant WDLS component, and 6 myxoid liposarcomas (MLSs). For all dedifferentiated liposarcoma cases, hibernoma-like histology was present only in the WDLS component. All tumors presented as large, deep-seated masses. Hibernoma-like histology resembled the pale cell, mixed cell, eosinophilic cell, or spindle cell subtypes of hibernoma, and it was a focal observation, with conventional liposarcoma histology coexisting in all cases. However, a few biopsy samples were predominated by hibernoma-like patterns, and 1 case was initially interpreted as hibernoma. Hibernoma-like components in WDLS immunohistochemically coexpressed MDM2 and CDK4 in most cases and harbored MDM2 amplification in tested cases, whereas half of the cases expressed UCP1. The hibernoma-like components of MLS expressed DDIT3, and DDIT3 rearrangements were present in the tested cases, whereas only negative or equivocal UCP1 expression was observed. In summary, WDLS and MLS focally demonstrate hibernoma-like histology on rare occasions. These elements are neoplastic, and some such areas in WDLS likely represent true brown fat differentiation, as supported by UCP1 expression. This pattern requires recognition to avoid the misdiagnosis as hibernoma, especially in biopsies. A careful search for classic liposarcoma histology and additional work-ups for the MDM2/CDK4 or DDIT3 status will be helpful for an accurate diagnosis.", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Naoki", "last_name": "Kojima", "name": null }, { "creator_type": "author", "first_name": "Motokiyo", "last_name": "Komiyama", "name": null }, { "creator_type": "author", "first_name": "Yasuo", "last_name": "Shinoda", "name": null }, { "creator_type": "author", "first_name": "Shun-Ichi", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null }, { "creator_type": "author", "first_name": "Akira", "last_name": "Kawai", "name": null }, { "creator_type": "author", "first_name": "Akihiko", "last_name": "Yoshida", "name": null } ], "identifiers": { "doi": { "normalized": "10.1097/pas.0000000000001911" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "35475774" } }, "mesh": [ { "descriptor": "Biopsy", "descriptor_ui": "D001706", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Lipoma", "descriptor_ui": "D008067", "major_topic": true }, { "descriptor": "Liposarcoma", "descriptor_ui": "D008080", "major_topic": true }, { "descriptor": "Liposarcoma, Myxoid", "descriptor_ui": "D018208", "major_topic": true }, { "descriptor": "Proto-Oncogene Proteins c-mdm2", "descriptor_ui": "D051736", "major_topic": false }, { "descriptor": "Uncoupling Protein 1", "descriptor_ui": "D000071256", "major_topic": false } ], "publication": { "conference_name": null, "date": "2022 Oct 1", "date_precision": "day", "issue": "10", "normalized_date": "2022-10-01", "pages": "1319-1328", "proceedings_title": null, "publisher": "", "title": "The American journal of surgical pathology", "volume": "46", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Liposarcoma With Hibernoma-like Histology: A Clinicopathologic Study of 16 Cases.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Problematic internet use (PIU) is increasingly recognized as a mental health concern, particularly among adolescents. The resting-state functional connectivity (rsFC) of the triple-network model has been described inconsistently in PIU. Using resting-state fMRI (rsFMRI) and hypothesizing a lower rsFC between default mode (DMN) and central executive networks (CEN) but a higher rsFC within the salience network (SN), this study scrutinized the neural substrates of PIU adolescents. A total of 30 adolescents with PIU and 30 control subjects underwent rsFMRI. The severity of PIU was evaluated by the Internet Addiction Test. Additionally, personality traits as well as emotional and behavioral problems were evaluated by the Temperament and Character Inventory (TCI) and the Strength and Difficulties Questionnaire (SDQ), respectively. Focusing on the DMN, SN, and CEN, we compared rsFC values between PIU and the control. Subsequently, within the combined group of subjects, TCI and SDQ correlation and mediation effects were investigated. Higher rsFC values of the left lateral prefrontal cortex (LPFC(L)) with the left anterior insula (aIns(L)) were observed for PIU than for the control, while rsFCs of the LPFC(L) with the medial PFC (MPFC), LPFC(L), as well as with the right lateral parietal cortex (LP(R)) were lower for PIU. Among these significant group differences, the rsFC between the LPFC(L) and MPFC was mediated by emotional symptoms (standardized beta = -0.12, 95% CI -0.29, -0.0052). The dysfunctional attention switching and incentive salience regulated by the SN were implicated as being a neural correlate of PIU, and this relationship would in part be explained by the emotional dysregulation associated with PIU in adolescents.", "classifications": [ { "id": "Fujiwara", "label": "Group Fujiwara", "parent": "Fujiwara", "type": "group" }, { "id": "Fujiwara", "label": "Team Fujiwara", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Kristiana", "last_name": "Siste", "name": null }, { "creator_type": "author", "first_name": "Jacub", "last_name": "Pandelaki", "name": null }, { "creator_type": "author", "first_name": "Jun", "last_name": "Miyata", "name": null }, { "creator_type": "author", "first_name": "Naoya", "last_name": "Oishi", "name": null }, { "creator_type": "author", "first_name": "Kosuke", "last_name": "Tsurumi", "name": null }, { "creator_type": "author", "first_name": "Hironobu", "last_name": "Fujiwara", "name": null }, { "creator_type": "author", "first_name": "Toshiya", "last_name": "Murai", "name": null }, { "creator_type": "author", "first_name": "Martina Wiwie", "last_name": "Nasrun", "name": null }, { "creator_type": "author", "first_name": "Tjhin", "last_name": "Wiguna", "name": null }, { "creator_type": "author", "first_name": "Saptawati", "last_name": "Bardosono", "name": null }, { "creator_type": "author", "first_name": "Rini", "last_name": "Sekartini", "name": null }, { "creator_type": "author", "first_name": "Riza", "last_name": "Sarasvita", "name": null }, { "creator_type": "author", "first_name": "Belinda Julivia", "last_name": "Murtani", "name": null }, { "creator_type": "author", "first_name": "Lee Thung", "last_name": "Sen", "name": null }, { "creator_type": "author", "first_name": "Karina Kalani", "last_name": "Firdaus", "name": null } ], "identifiers": { "doi": { "normalized": "10.3390/jcm11195838" }, "pmcid": { "normalized": "PMC9570959" }, "pmid": { "normalized": "36233704" } }, "mesh": [], "publication": { "conference_name": null, "date": "2022 Oct 1", "date_precision": "day", "issue": "19", "normalized_date": "2022-10-01", "pages": "5838", "proceedings_title": null, "publisher": "", "title": "Journal of clinical medicine", "volume": "11", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Altered Resting-State Network in Adolescents with Problematic Internet Use.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "PURPOSE: To gain new insights into the etiology of blepharitis, we investigated the causative bacteria in patients with blepharitis and the effects of 1% azithromycin ophthalmic solution. STUDY DESIGN: A multicenter, prospective observational study. METHODS: After the subjects were diagnosed as having blepharitis they were administered 1% azithromycin ophthalmic solution for up to 14 days. Bacterial cultures and smear microscopic examinations of the eyelid margin were conducted at the initial visit, after administering eye drops, and 1 month after the end of eye drop administration. The minimum inhibitory concentrations (MICs) of azithromycin were measured. RESULTS: At the initial visit, the bacterial morphology determined by smear microscopic examinations coincided with that of strains isolated by culture taken from 22 of 45 patients. All detected bacteria were gram-positive, and Corynebacterium spp., Cutibacterium acnes, Staphylococcus epidermidis, Streptococcus spp., and Enterococcus faecalis were isolated most commonly. Compared with the initial visit the number of isolated strains per eye decreased significantly at 7 days after the start of eye drop administration and 1 month after the end of eye drop administration. The azithromycin MICs were temporarily increased after the start of eye drops but then decreased. CONCLUSION: Our study suggests that in blepharitis pathogenicity is characterized by increased strain numbers and amounts of indigenous bacteria. Administering a 1% azithromycin ophthalmic solution suppresses the number of bacterial strains within 1 month after the end of eye drop administration without increasing drug resistance.", "classifications": [ { "id": "Suzuki", "label": "Group Suzuki", "parent": "Takekawa", "type": "group" }, { "id": "Takekawa", "label": "Team Takekawa", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Ryohei", "last_name": "Nejima", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Eguchi", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Todokoro", "name": null }, { "creator_type": "author", "first_name": "Tomoyuki", "last_name": "Inoue", "name": null }, { "creator_type": "author", "first_name": "Yuichi", "last_name": "Kaji", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Takaaki", "last_name": "Hattori", "name": null }, { "creator_type": "author", "first_name": "Saichi", "last_name": "Hoshi", "name": null }, { "creator_type": "author", "first_name": "Yumi", "last_name": "Sasaki", "name": null }, { "creator_type": "author", "first_name": "Yoshitsugu", "last_name": "Inoue", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/s10384-022-00947-8" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "36181644" } }, "mesh": [ { "descriptor": "Anti-Bacterial Agents", "descriptor_ui": "D000900", "major_topic": false }, { "descriptor": "Azithromycin", "descriptor_ui": "D017963", "major_topic": true }, { "descriptor": "Bacteria", "descriptor_ui": "D001419", "major_topic": false }, { "descriptor": "Blepharitis", "descriptor_ui": "D001762", "major_topic": true }, { "descriptor": "Clinical Protocols", "descriptor_ui": "D002985", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Multicenter Studies as Topic", "descriptor_ui": "D015337", "major_topic": false }, { "descriptor": "Observational Studies as Topic", "descriptor_ui": "D064887", "major_topic": false }, { "descriptor": "Ophthalmic Solutions", "descriptor_ui": "D009883", "major_topic": false }, { "descriptor": "Treatment Outcome", "descriptor_ui": "D016896", "major_topic": false } ], "publication": { "conference_name": null, "date": "2022 Oct 1", "date_precision": "day", "issue": "", "normalized_date": "2022-10-01", "pages": "", "proceedings_title": null, "publisher": "", "title": "Japanese journal of ophthalmology", "volume": "", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Analysis of treatment protocols using azithromycin eye drops for bacterial blepharitis: second report-bacteriological investigation.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The ability to engineer complex multicellular systems has enormous potential to inform our understanding of biological processes and disease and alter the drug development process. Engineering living systems to emulate natural processes or to incorporate new functions relies on a detailed understanding of the biochemical, mechanical, and other cues between cells and between cells and their environment that result in the coordinated action of multicellular systems. On April 3-6, 2022, experts in the field met at the Keystone symposium \"Engineering Multicellular Living Systems\" to discuss recent advances in understanding how cells cooperate within a multicellular system, as well as recent efforts to engineer systems like organ-on-a-chip models, biological robots, and organoids. Given the similarities and common themes, this meeting was held in conjunction with the symposium \"Organoids as Tools for Fundamental Discovery and Translation\".", "classifications": [ { "id": "Morishita", "label": "Group Morishita", "parent": "Morishita", "type": "group" }, { "id": "Morishita", "label": "Team Morishita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Jennifer", "last_name": "Cable", "name": null }, { "creator_type": "author", "first_name": "Paola", "last_name": "Arlotta", "name": null }, { "creator_type": "author", "first_name": "Kevin Kit", "last_name": "Parker", "name": null }, { "creator_type": "author", "first_name": "Alex J.", "last_name": "Hughes", "name": null }, { "creator_type": "author", "first_name": "Katharine", "last_name": "Goodwin", "name": null }, { "creator_type": "author", "first_name": "Christine L.", "last_name": "Mummery", "name": null }, { "creator_type": "author", "first_name": "Roger D.", "last_name": "Kamm", "name": null }, { "creator_type": "author", "first_name": "Sandra J.", "last_name": "Engle", "name": null }, { "creator_type": "author", "first_name": "Danilo A.", "last_name": "Tagle", "name": null }, { "creator_type": "author", "first_name": "Sylvia F.", "last_name": "Boj", "name": null }, { "creator_type": "author", "first_name": "Alice E.", "last_name": "Stanton", "name": null }, { "creator_type": "author", "first_name": "Yoshihiro", "last_name": "Morishita", "name": null }, { "creator_type": "author", "first_name": "Melissa L.", "last_name": "Kemp", "name": null }, { "creator_type": "author", "first_name": "Dennis A.", "last_name": "Norfleet", "name": null }, { "creator_type": "author", "first_name": "Elebeoba E.", "last_name": "May", "name": null }, { "creator_type": "author", "first_name": "Aric", "last_name": "Lu", "name": null }, { "creator_type": "author", "first_name": "Rashid", "last_name": "Bashir", "name": null }, { "creator_type": "author", "first_name": "Adam W.", "last_name": "Feinberg", "name": null }, { "creator_type": "author", "first_name": "Sarah M.", "last_name": "Hull", "name": null }, { "creator_type": "author", "first_name": "Anjelica L.", "last_name": "Gonzalez", "name": null }, { "creator_type": "author", "first_name": "Michael R.", "last_name": "Blatchley", "name": null }, { "creator_type": "author", "first_name": "Nuria", "last_name": "Montserrat Pulido", "name": null }, { "creator_type": "author", "first_name": "Ryuji", "last_name": "Morizane", "name": null }, { "creator_type": "author", "first_name": "Todd C.", "last_name": "McDevitt", "name": null }, { "creator_type": "author", "first_name": "Deepak", "last_name": "Mishra", "name": null }, { "creator_type": "author", "first_name": "Adriana", "last_name": "Mulero-Russe", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/nyas.14896" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "36177947" } }, "mesh": [ { "descriptor": "Engineering", "descriptor_ui": "D004738", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Organoids", "descriptor_ui": "D009940", "major_topic": true }, { "descriptor": "Tissue Engineering", "descriptor_ui": "D023822", "major_topic": false } ], "publication": { "conference_name": null, "date": "2022 Sep 30", "date_precision": "day", "issue": "", "normalized_date": "2022-09-30", "pages": "", "proceedings_title": null, "publisher": "", "title": "Annals of the New York Academy of Sciences", "volume": "", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Engineering multicellular living systems-A Keystone Symposia report.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Immunotherapy including immune checkpoint inhibitors (ICIs) has become the backbone of treatment for the majority of lung cancers with advanced or metastatic disease. In addition, they have increasingly been used for early-stage tumors in neoadjuvant and adjuvant settings. Unfortunately, however, only a subset of patients experiences meaningful response to ICIs. While PD-L1 protein expression by immunohistochemistry (IHC) has played a role as the principle predictive biomarker for immunotherapy, its performance may not be optimal, and it suffers multiple practical issues with different companion diagnostic assays approved. Similarly, tumor mutation burden (TMB) has multiple technical issues as a predictive biomarker for ICIs. Now, ongoing research on tumor and host immune-specific factors has identified immunotherapy biomarkers that may provide better response and prognosis prediction, in particular in a multimodal approach. This review by the IASLC Pathology Committee provides an overview of various immunotherapy biomarkers including updated data on PD-L1 IHC and TMB, and assesssments of neoantigens, genetic and epigenetic signatures, immune microenvironment by IHC and transcriptomics, as well as microbiome and pathological response to neoadjuvant immunotherapies. The aim of this review is to underline the efficacy of new individual or combined predictive biomarkers beyond PD-L1 IHC and TMB.", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Mari", "last_name": "Mino-Kenudson", "name": null }, { "creator_type": "author", "first_name": "Kurt", "last_name": "Schalper", "name": null }, { "creator_type": "author", "first_name": "Wendy", "last_name": "Cooper", "name": null }, { "creator_type": "author", "first_name": "Sanja", "last_name": "Dacic", "name": null }, { "creator_type": "author", "first_name": "Fred R.", "last_name": "Hirsch", "name": null }, { "creator_type": "author", "first_name": "Deepali", "last_name": "Jain", "name": null }, { "creator_type": "author", "first_name": "Fernando", "last_name": "Lopez-Rios", "name": null }, { "creator_type": "author", "first_name": "Ming Sound", "last_name": "Tsao", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null }, { "creator_type": "author", "first_name": "Mary Beth", "last_name": "Beasley", "name": null }, { "creator_type": "author", "first_name": "Hui", "last_name": "Yu", "name": null }, { "creator_type": "author", "first_name": "Lynette M.", "last_name": "Sholl", "name": null }, { "creator_type": "author", "first_name": "Elizabeth", "last_name": "Brambilla", "name": null }, { "creator_type": "author", "first_name": "Teh-Ying", "last_name": "Chou", "name": null }, { "creator_type": "author", "first_name": "Casey", "last_name": "Connolly", "name": null }, { "creator_type": "author", "first_name": "Ignacio", "last_name": "Wistuba", "name": null }, { "creator_type": "author", "first_name": "Keith M.", "last_name": "Kerr", "name": null }, { "creator_type": "author", "first_name": "Sylvie", "last_name": "Lantuejoul", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.jtho.2022.09.109" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "36184066" } }, "mesh": [ { "descriptor": "B7-H1 Antigen", "descriptor_ui": "D060890", "major_topic": false }, { "descriptor": "Biomarkers, Tumor", "descriptor_ui": "D014408", "major_topic": false }, { "descriptor": "Carcinoma, Non-Small-Cell Lung", "descriptor_ui": "D002289", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Immunotherapy", "descriptor_ui": "D007167", "major_topic": false }, { "descriptor": "Lung Neoplasms", "descriptor_ui": "D008175", "major_topic": true }, { "descriptor": "Tumor Microenvironment", "descriptor_ui": "D059016", "major_topic": false } ], "publication": { "conference_name": null, "date": "2022 Sep 29", "date_precision": "day", "issue": "", "normalized_date": "2022-09-29", "pages": "S1556-0864(22)01695-1", "proceedings_title": null, "publisher": "", "title": "Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer", "volume": "", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Predictive Biomarkers for Immunotherapy in Lung Cancer: Perspective from the IASLC Pathology Committee.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Cardiovascular disease is the most common comorbidity in chronic kidney disease (CKD) patients, affecting both their prognosis and quality of life. Cardiac fibrosis is common in CKD patients with left ventricular diastolic dysfunction, and it is associated with increased risk of heart failure and mortality. Recent evidence suggests that high salt intake activates immune responses associated with local accumulation of sodium. We reported that high salt intake promotes cardiac inflammation in subtotal nephrectomized (Nx) mice. We investigated the effects of administration of MR16-1, a rat anti-mouse monoclonal interleukin (IL)-6 receptor antibody, in Nx mice with salt loading (Nx-salt). Expression of monocyte chemoattractant protein (MCP)-1, tumor necrosis factor (TNF)-a, IL-1b, and IL-6 mRNAs and macrophage infiltration was significantly reduced in the heart of Nx-salt mice treated with MR16-1 (Nx-salt-MR16-1) as compared with Nx-salt mice treated with control rat immunoglobulin G1 (rat IgG1) (Nx-salt-rat IgG1). Correspondingly, cardiac fibrosis was significantly attenuated in Nx-salt-MR16-1 mice compared with Nx-salt-rat IgG1 mice. Furthermore, in the heart of Nx-salt-MR16-1 mice, expression of mRNA for nicotinamide adenine dinucleotide phosphate oxidase-2, an oxidative stress marker, was significantly downregulated compared with Nx-salt-rat IgG1 mice. Increases in cardiac metabolites including histidine and γ-butyrobetaine were also reversed by IL-6 blockade treatment. In conclusion, IL-6 blockade exerts anti-inflammatory, anti-fibrotic, and partial anti-oxidative effects in the heart of Nx-salt mice.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Hiroya", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Ting", "last_name": "Sun", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Kinashi", "name": null }, { "creator_type": "author", "first_name": "Keisuke", "last_name": "Kamiya", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Yamaguchi", "name": null }, { "creator_type": "author", "first_name": "Hironobu", "last_name": "Nobata", "name": null }, { "creator_type": "author", "first_name": "Fumiko", "last_name": "Sakata", "name": null }, { "creator_type": "author", "first_name": "Hangsoo", "last_name": "Kim", "name": null }, { "creator_type": "author", "first_name": "Masashi", "last_name": "Mizuno", "name": null }, { "creator_type": "author", "first_name": "Shunnosuke", "last_name": "Kunoki", "name": null }, { "creator_type": "author", "first_name": "Yukinao", "last_name": "Sakai", "name": null }, { "creator_type": "author", "first_name": "Akiyoshi", "last_name": "Hirayama", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Kazuhiro", "last_name": "Yoshikawa", "name": null }, { "creator_type": "author", "first_name": "Takuji", "last_name": "Ishimoto", "name": null }, { "creator_type": "author", "first_name": "Yasuhiko", "last_name": "Ito", "name": null } ], "identifiers": { "doi": { "normalized": "10.1152/ajprenal.00396.2021" }, "pmcid": { "normalized": null }, "pmid": { "normalized": null } }, "mesh": [], "publication": { "conference_name": null, "date": "2022-09-29", "date_precision": "day", "issue": "", "normalized_date": "2022-09-29", "pages": "", "proceedings_title": null, "publisher": "American Physiological Society", "title": "American Journal of Physiology-Renal Physiology", "volume": "", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Interleukin-6 blockade reduces salt-induced cardiac inflammation and fibrosis in subtotal nephrectomized mice", "url": "https://journals.physiology.org/doi/abs/10.1152/ajprenal.00396.2021", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Vanishing bile duct syndrome (VBDS) is a rare hepatic disorder which leads to liver failure as a result of progressive destruction of the intrahepatic bile ducts. There are no treatment modalities for VBDS itself and severe hepatic dysfunction restricts the treatment of underlying diseases. We safely treated a case of classic Hodgkin lymphoma (HL) with VBDS using brentuximab vedotin (BV). The patient was treated with 5 cycles of reduced BV and a partial metabolic response was obtained. Moreover, a standard dose of BV for another 5 cycles was accomplished with minimal adverse events. Our experience indicates that BV could be a treatment option for classic HL with VBDS.", "classifications": [ { "id": "Nishikii", "label": "Group Nishikii", "parent": "Shintaku", "type": "group" }, { "id": "Shintaku", "label": "Team Shintaku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Kantaro", "last_name": "Ishitsuka", "name": null }, { "creator_type": "author", "first_name": "Yasuhisa", "last_name": "Yokoyama", "name": null }, { "creator_type": "author", "first_name": "Naoko", "last_name": "Baba", "name": null }, { "creator_type": "author", "first_name": "Ryota", "last_name": "Matsuoka", "name": null }, { "creator_type": "author", "first_name": "Noriaki", "last_name": "Sakamoto", "name": null }, { "creator_type": "author", "first_name": "Tatsuhiro", "last_name": "Sakamoto", "name": null }, { "creator_type": "author", "first_name": "Manabu", "last_name": "Kusakabe", "name": null }, { "creator_type": "author", "first_name": "Takayasu", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Naoki", "last_name": "Kurita", "name": null }, { "creator_type": "author", "first_name": "Hidekazu", "last_name": "Nishikii", "name": null }, { "creator_type": "author", "first_name": "Mamiko", "last_name": "Sakata-Yanagimoto", "name": null }, { "creator_type": "author", "first_name": "Naoshi", "last_name": "Obara", "name": null }, { "creator_type": "author", "first_name": "Yuichi", "last_name": "Hasegawa", "name": null }, { "creator_type": "author", "first_name": "Shigeru", "last_name": "Chiba", "name": null } ], "identifiers": { "doi": { "normalized": "10.3960/jslrt.21035" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "35831099" } }, "mesh": [ { "descriptor": "Bile Ducts, Intrahepatic", "descriptor_ui": "D001653", "major_topic": false }, { "descriptor": "Brentuximab Vedotin", "descriptor_ui": "D000079963", "major_topic": false }, { "descriptor": "Hodgkin Disease", "descriptor_ui": "D006689", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Liver Failure", "descriptor_ui": "D017093", "major_topic": true } ], "publication": { "conference_name": null, "date": "2022 Sep 28", "date_precision": "day", "issue": "3", "normalized_date": "2022-09-28", "pages": "154-157", "proceedings_title": null, "publisher": "", "title": "Journal of clinical and experimental hematopathology : JCEH", "volume": "62", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Administration of brentuximab vedotin to a Hodgkin lymphoma patient with liver dysfunction due to vanishing bile duct syndrome resulting in a partial response without any severe adverse events.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Tubulin post-translational modifications (PTMs) alter microtubule properties by affecting the binding of microtubule-associated proteins (MAPs). Microtubule detyrosination, which occurs by proteolytic removal of the C-terminal tyrosine from a-tubulin, generates the oldest known tubulin PTM, but we lack comprehensive knowledge of MAPs that are regulated by this PTM. We developed a screening pipeline to identify proteins that discriminate between Y- and DeltaY-microtubules and found that echinoderm microtubule-associated protein-like 2 (EML2) preferentially interacts with Y-microtubules. This activity depends on a Y-microtubule interaction motif built from WD40 repeats. We show that EML2 tracks the tips of shortening microtubules, a behavior not previously seen among human MAPs in vivo, and influences dynamics to increase microtubule stability. Our screening pipeline is readily adapted to identify proteins that specifically recognize a wide range of microtubule PTMs.", "classifications": [ { "id": "Higaki", "label": "Group Higaki", "parent": "Ueda", "type": "group" }, { "id": "Ueda", "label": "Team Ueda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Takashi", "last_name": "Hotta", "name": null }, { "creator_type": "author", "first_name": "Thomas S.", "last_name": "McAlear", "name": null }, { "creator_type": "author", "first_name": "Yang", "last_name": "Yue", "name": null }, { "creator_type": "author", "first_name": "Takumi", "last_name": "Higaki", "name": null }, { "creator_type": "author", "first_name": "Sarah E.", "last_name": "Haynes", "name": null }, { "creator_type": "author", "first_name": "Alexey I.", "last_name": "Nesvizhskii", "name": null }, { "creator_type": "author", "first_name": "David", "last_name": "Sept", "name": null }, { "creator_type": "author", "first_name": "Kristen J.", "last_name": "Verhey", "name": null }, { "creator_type": "author", "first_name": "Susanne", "last_name": "Bechstedt", "name": null }, { "creator_type": "author", "first_name": "Ryoma", "last_name": "Ohi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.cub.2022.07.027" }, "pmcid": { "normalized": "PMC9530018" }, "pmid": { "normalized": "35963242" } }, "mesh": [ { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Microtubule-Associated Proteins", "descriptor_ui": "D008869", "major_topic": false }, { "descriptor": "Microtubules", "descriptor_ui": "D008870", "major_topic": true }, { "descriptor": "Protein Processing, Post-Translational", "descriptor_ui": "D011499", "major_topic": false }, { "descriptor": "Tubulin", "descriptor_ui": "D014404", "major_topic": true }, { "descriptor": "Tyrosine", "descriptor_ui": "D014443", "major_topic": false } ], "publication": { "conference_name": null, "date": "2022 Sep 26", "date_precision": "day", "issue": "18", "normalized_date": "2022-09-26", "pages": "3898-3910.e14", "proceedings_title": null, "publisher": "", "title": "Current biology : CB", "volume": "32", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "EML2-S constitutes a new class of proteins that recognizes and regulates the dynamics of tyrosinated microtubules.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "In the initial process of coronavirus disease 2019 (COVID-19), severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infects respiratory epithelial cells and then transfers to other organs the blood vessels. It is believed that SARS-CoV-2 can pass the vascular wall by altering the endothelial barrier using an unknown mechanism. In this study, we investigated the effect of SARS-CoV-2 on the endothelial barrier using an airway-on-a-chip that mimics respiratory organs and found that SARS-CoV-2 produced from infected epithelial cells disrupts the barrier by decreasing Claudin-5 (CLDN5), a tight junction protein, and disrupting vascular endothelial cadherin-mediated adherens junctions. Consistently, the gene and protein expression levels of CLDN5 in the lungs of a patient with COVID-19 were decreased. CLDN5 overexpression or Fluvastatin treatment rescued the SARS-CoV-2-induced respiratory endothelial barrier disruption. We concluded that the down-regulation of CLDN5 expression is a pivotal mechanism for SARS-CoV-2-induced endothelial barrier disruption in respiratory organs and that inducing CLDN5 expression is a therapeutic strategy against COVID-19.", "classifications": [ { "id": "Yamamoto", "label": "Group Yamamoto", "parent": "Toyoshima", "type": "group" }, { "id": "Toyoshima", "label": "Team Toyoshima", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Rina", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Junya", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Keisuke", "last_name": "Shirakura", "name": null }, { "creator_type": "author", "first_name": "Risa", "last_name": "Funatsu", "name": null }, { "creator_type": "author", "first_name": "Kaori", "last_name": "Kosugi", "name": null }, { "creator_type": "author", "first_name": "Sayaka", "last_name": "Deguchi", "name": null }, { "creator_type": "author", "first_name": "Masaki", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Yugo", "last_name": "Tsunoda", "name": null }, { "creator_type": "author", "first_name": "Maaya", "last_name": "Morita", "name": null }, { "creator_type": "author", "first_name": "Kosuke", "last_name": "Muraoka", "name": null }, { "creator_type": "author", "first_name": "Masato", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Tomoaki", "last_name": "Kanbara", "name": null }, { "creator_type": "author", "first_name": "Shota", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Shigeyuki", "last_name": "Tamiya", "name": null }, { "creator_type": "author", "first_name": "Nagisa", "last_name": "Tokunoh", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Kawai", "name": null }, { "creator_type": "author", "first_name": "Masahito", "last_name": "Ikawa", "name": null }, { "creator_type": "author", "first_name": "Chikako", "last_name": "Ono", "name": null }, { "creator_type": "author", "first_name": "Keisuke", "last_name": "Tachibana", "name": null }, { "creator_type": "author", "first_name": "Masuo", "last_name": "Kondoh", "name": null }, { "creator_type": "author", "first_name": "Masanori", "last_name": "Obana", "name": null }, { "creator_type": "author", "first_name": "Yoshiharu", "last_name": "Matsuura", "name": null }, { "creator_type": "author", "first_name": "Akihiro", "last_name": "Ohsumi", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Noda", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Yasuo", "last_name": "Yoshioka", "name": null }, { "creator_type": "author", "first_name": "Yu-Suke", "last_name": "Torisawa", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Date", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Fujio", "name": null }, { "creator_type": "author", "first_name": "Miki", "last_name": "Nagao", "name": null }, { "creator_type": "author", "first_name": "Kazuo", "last_name": "Takayama", "name": null }, { "creator_type": "author", "first_name": "Yoshiaki", "last_name": "Okada", "name": null } ], "identifiers": { "doi": { "normalized": "10.1126/sciadv.abo6783" }, "pmcid": { "normalized": "PMC9491726" }, "pmid": { "normalized": "36129989" } }, "mesh": [ { "descriptor": "Claudin-5", "descriptor_ui": "D062507", "major_topic": false }, { "descriptor": "COVID-19", "descriptor_ui": "D000086382", "major_topic": true }, { "descriptor": "Endothelial Cells", "descriptor_ui": "D042783", "major_topic": false }, { "descriptor": "Fluvastatin", "descriptor_ui": "D000077340", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "SARS-CoV-2", "descriptor_ui": "D000086402", "major_topic": true }, { "descriptor": "Tight Junction Proteins", "descriptor_ui": "D062725", "major_topic": false } ], "publication": { "conference_name": null, "date": "2022 Sep 23", "date_precision": "day", "issue": "38", "normalized_date": "2022-09-23", "pages": "eabo6783", "proceedings_title": null, "publisher": "", "title": "Science advances", "volume": "8", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "SARS-CoV-2 disrupts respiratory vascular barriers by suppressing Claudin-5 expression.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Chemotaxis, the migration of cells in response to chemical stimulus, is an important concept in the angiogenesis model. In most angiogenesis models, chemotaxis is defined as the migration of a sprout tip in response to the upgradient of the VEGF (vascular endothelial growth factor). However, we found that angiogenesis induced by performing arterial patch grafting on rabbits occurred under the decreasing VEGFA gradient. Data show that the VEGFA concentration peaked at approximately 0.3 to 0.5 cm away from the arterial patch and decreased as the measurement approaches the patch. We also observed that the new blood vessels formed are twisted and congested in some areas, in a distinguishable manner from non-pathological blood vessels. To explain these observations, we developed a mathematical model and compared the results from numerical simulations with the experimental data. We introduced a new chemotactic velocity using the temporal change in the chemoattractant gradient to govern the sprout tip migration. We performed a hybrid simulation to illustrate the growth of new vessels. Results indicated the speed of growth of new vessels oscillated before reaching the periphery of the arterial patch. Crowded and congested blood vessel formation was observed during numerical simulations. Thus, our numerical simulation results agreed with the experimental data.", "classifications": [ { "id": "JPMJCR2022", "label": "JPMJCR2022", "researcher": "Mutsuhiro Takekawa", "type": "grant" }, { "id": "Suzuki", "label": "Group Suzuki", "parent": "Takekawa", "type": "group" }, { "id": "Takekawa", "label": "Group Takekawa", "parent": "Takekawa", "type": "group" }, { "id": "Takekawa", "label": "Team Takekawa", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Dhisa", "last_name": "Minerva", "name": null }, { "creator_type": "author", "first_name": "Nuha Loling", "last_name": "Othman", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Nakazawa", "name": null }, { "creator_type": "author", "first_name": "Yukinobu", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Akiteru", "last_name": "Goto", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Suzuki", "name": null } ], "identifiers": { "doi": { "normalized": "10.3390/ijms231911208" }, "pmcid": { "normalized": "PMC9569559" }, "pmid": { "normalized": "36232507" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Chemotactic Factors", "descriptor_ui": "D002630", "major_topic": false }, { "descriptor": "Chemotaxis", "descriptor_ui": "D002633", "major_topic": false }, { "descriptor": "Neovascularization, Pathologic", "descriptor_ui": "D009389", "major_topic": true }, { "descriptor": "Neovascularization, Physiologic", "descriptor_ui": "D018919", "major_topic": false }, { "descriptor": "Rabbits", "descriptor_ui": "D011817", "major_topic": false }, { "descriptor": "Vascular Endothelial Growth Factor A", "descriptor_ui": "D042461", "major_topic": true }, { "descriptor": "Vascular Endothelial Growth Factors", "descriptor_ui": "D042442", "major_topic": false } ], "publication": { "conference_name": null, "date": "2022 Sep 23", "date_precision": "day", "issue": "19", "normalized_date": "2022-09-23", "pages": "11208", "proceedings_title": null, "publisher": "", "title": "International journal of molecular sciences", "volume": "23", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "A New Chemotactic Mechanism Governs Long-Range Angiogenesis Induced by Patching an Arterial Graft into a Vein.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "With age, senescence-associated (SA) CD4(+) T cells that are refractory to T cell receptor (TCR) stimulation are increased along with spontaneous germinal center (Spt-GC) development prone to autoantibody production. We demonstrate that CD153 and its receptor CD30 are expressed in SA-T and Spt-GC B cells, respectively, and deficiency of either CD153 or CD30 results in the compromised increase of both cell types. CD153 engagement on SA-T cells upon TCR stimulation causes association of CD153 with the TCR/CD3 complex and restores TCR signaling, whereas CD30 engagement on GC B cells induces their expansion. Administration of an anti-CD153 antibody blocking the interaction with CD30 suppresses the increase in both SA-T and Spt-GC B cells with age and ameliorates lupus in lupus-prone mice. These results suggest that the molecular interaction of CD153 and CD30 plays a central role in the reciprocal activation of SA-T and Spt-GC B cells, leading to immunosenescent phenotypes and autoimmunity.", "classifications": [], "creators": [ { "creator_type": "author", "first_name": "Yuji", "last_name": "Fukushima", "name": null }, { "creator_type": "author", "first_name": "Keiko", "last_name": "Sakamoto", "name": null }, { "creator_type": "author", "first_name": "Michiyuki", "last_name": "Matsuda", "name": null }, { "creator_type": "author", "first_name": "Yasunobu", "last_name": "Yoshikai", "name": null }, { "creator_type": "author", "first_name": "Hideo", "last_name": "Yagita", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Kitamura", "name": null }, { "creator_type": "author", "first_name": "Misaki", "last_name": "Chihara", "name": null }, { "creator_type": "author", "first_name": "Nagahiro", "last_name": "Minato", "name": null }, { "creator_type": "author", "first_name": "Masakazu", "last_name": "Hattori", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.celrep.2022.111373" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "36130493" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "CD3 Complex", "descriptor_ui": "D017252", "major_topic": false }, { "descriptor": "CD30 Ligand", "descriptor_ui": "D053285", "major_topic": false }, { "descriptor": "Germinal Center", "descriptor_ui": "D018858", "major_topic": false }, { "descriptor": "Ki-1 Antigen", "descriptor_ui": "D017730", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Receptors, Antigen, T-Cell", "descriptor_ui": "D011948", "major_topic": true }, { "descriptor": "T-Lymphocytes", "descriptor_ui": "D013601", "major_topic": true } ], "publication": { "conference_name": null, "date": "2022 Sep 20", "date_precision": "day", "issue": "12", "normalized_date": "2022-09-20", "pages": "111373", "proceedings_title": null, "publisher": "", "title": "Cell reports", "volume": "40", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "cis interaction of CD153 with TCR/CD3 is crucial for the pathogenic activation of senescence-associated T cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "", "classifications": [ { "id": "Nishikii", "label": "Group Nishikii", "parent": "Shintaku", "type": "group" }, { "id": "Shintaku", "label": "Team Shintaku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Kantaro", "last_name": "Ishitsuka", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Yoshizawa", "name": null }, { "creator_type": "author", "first_name": "Hidekazu", "last_name": "Nishikii", "name": null }, { "creator_type": "author", "first_name": "Manabu", "last_name": "Kusakabe", "name": null }, { "creator_type": "author", "first_name": "Yufu", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Yukinori", "last_name": "Inadome", "name": null }, { "creator_type": "author", "first_name": "Tatsuhiro", "last_name": "Sakamoto", "name": null }, { "creator_type": "author", "first_name": "Takayasu", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Naoki", "last_name": "Kurita", "name": null }, { "creator_type": "author", "first_name": "Yasuhisa", "last_name": "Yokoyama", "name": null }, { "creator_type": "author", "first_name": "Naoshi", "last_name": "Obara", "name": null }, { "creator_type": "author", "first_name": "Yuichi", "last_name": "Hasegawa", "name": null }, { "creator_type": "author", "first_name": "Yasuhito", "last_name": "Nannya", "name": null }, { "creator_type": "author", "first_name": "Seishi", "last_name": "Ogawa", "name": null }, { "creator_type": "author", "first_name": "Mamiko", "last_name": "Sakata-Yanagimoto", "name": null }, { "creator_type": "author", "first_name": "Shigeru", "last_name": "Chiba", "name": null } ], "identifiers": { "doi": { "normalized": "10.1080/10428194.2022.2123235" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "36126964" } }, "mesh": [ { "descriptor": "AMP-Activated Protein Kinase Kinases", "descriptor_ui": "D000091162", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Leukemia, Mast-Cell", "descriptor_ui": "D007946", "major_topic": true }, { "descriptor": "Mast Cells", "descriptor_ui": "D008407", "major_topic": false }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": false }, { "descriptor": "Proto-Oncogene Proteins c-kit", "descriptor_ui": "D019009", "major_topic": false }, { "descriptor": "Translocation, Genetic", "descriptor_ui": "D014178", "major_topic": false } ], "publication": { "conference_name": null, "date": "2022 Sep 20", "date_precision": "day", "issue": "", "normalized_date": "2022-09-20", "pages": "1-5", "proceedings_title": null, "publisher": "", "title": "Leukemia & lymphoma", "volume": "", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Novel translocation of POGZ/STK11 in de novo mast cell leukemia with KIT D816H mutation.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Capillary electrophoresis mass spectrometry (CE-MS) can measure the intracellular amount of highly polar and charged metabolites; liquid chromatography mass spectrometry (LC-MS) can quantify hydrophobic metabolites. A comprehensive metabolome analysis requires independent sample preparation for LC-MS and CE-MS. Here, we present a protocol to prepare for sequentially analyzing the metabolites from one sample. Here we describe the steps for breast cancer cell lines, MCF-7 cells, but the protocol can be applied to other cell types.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Ryuhei", "last_name": "Kudo", "name": null }, { "creator_type": "author", "first_name": "Kaori", "last_name": "Igarashi", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Takamasa", "last_name": "Ishikawa", "name": null }, { "creator_type": "author", "first_name": "Yasuhiro", "last_name": "Saito", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.xpro.2022.101531" }, "pmcid": { "normalized": "PMC9283946" }, "pmid": { "normalized": "35819883" } }, "mesh": [ { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Mass Spectrometry", "descriptor_ui": "D013058", "major_topic": false }, { "descriptor": "Metabolome", "descriptor_ui": "D055442", "major_topic": true }, { "descriptor": "Metabolomics", "descriptor_ui": "D055432", "major_topic": true } ], "publication": { "conference_name": null, "date": "2022 Sep 16", "date_precision": "day", "issue": "3", "normalized_date": "2022-09-16", "pages": "101531", "proceedings_title": null, "publisher": "", "title": "STAR protocols", "volume": "3", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Comprehensive metabolome analysis of intracellular metabolites in cultured cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Ductal carcinoma in situ (DCIS) is a precursor to invasive breast cancer. The frequency of DCIS is increasing because of routine mammography; however, the biological features and intratumoral heterogeneity of DCIS remain obscure. To address this deficiency, we performed single-cell transcriptomic profiling of DCIS and invasive ductal carcinoma (IDC). DCIS was found to be composed of several transcriptionally distinct subpopulations of cancer cells with specific functions. Several transcripts, including long noncoding RNAs, were highly expressed in IDC compared with DCIS and might be related to the invasive phenotype. Closeness centrality analysis revealed extensive heterogeneity in DCIS, and the prediction model for cell-to-cell interactions implied that the interaction network among luminal cells and immune cells in DCIS was comparable with that in IDC. In addition, transcriptomic profiling of HER2+ luminal DCIS indicated HER2 genomic amplification at the DCIS stage. These data provide novel insight into the intratumoral heterogeneity and molecular features of DCIS, which exhibit properties similar to IDC. SIGNIFICANCE: Investigation of the molecular features of ductal carcinoma in situ at single cell resolution provides new insights into breast cancer biology and identifies candidate therapeutic targets and diagnostic biomarkers.", "classifications": [ { "id": "Okamoto", "label": "Group Okamoto", "parent": "Okamoto", "type": "group" }, { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Momoko", "last_name": "Tokura", "name": null }, { "creator_type": "author", "first_name": "Jun", "last_name": "Nakayama", "name": null }, { "creator_type": "author", "first_name": "Marta", "last_name": "Prieto-Vila", "name": null }, { "creator_type": "author", "first_name": "Sho", "last_name": "Shiino", "name": null }, { "creator_type": "author", "first_name": "Masayuki", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Tomofumi", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Naoaki", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Shin", "last_name": "Takayama", "name": null }, { "creator_type": "author", "first_name": "Yutaka", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Okamoto", "name": null }, { "creator_type": "author", "first_name": "Takahiro", "last_name": "Ochiya", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Kohno", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null }, { "creator_type": "author", "first_name": "Akihiko", "last_name": "Suto", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Yamamoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1158/0008-5472.can-22-0090" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "35852797" } }, "mesh": [ { "descriptor": "Biomarkers", "descriptor_ui": "D015415", "major_topic": false }, { "descriptor": "Breast Neoplasms", "descriptor_ui": "D001943", "major_topic": true }, { "descriptor": "Carcinoma, Ductal, Breast", "descriptor_ui": "D018270", "major_topic": true }, { "descriptor": "Carcinoma, Intraductal, Noninfiltrating", "descriptor_ui": "D002285", "major_topic": true }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Gene Expression Profiling", "descriptor_ui": "D020869", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false } ], "publication": { "conference_name": null, "date": "2022 Sep 16", "date_precision": "day", "issue": "18", "normalized_date": "2022-09-16", "pages": "3236-3248", "proceedings_title": null, "publisher": "", "title": "Cancer research", "volume": "82", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Single-Cell Transcriptome Profiling Reveals Intratumoral Heterogeneity and Molecular Features of Ductal Carcinoma In Situ.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Phenotypic alterations in the lung epithelium have been widely implicated in Chronic obstructive pulmonary disease (COPD) pathogenesis, but the precise mechanisms orchestrating this persistent inflammatory process remain unknown due to the complexity of lung parenchymal and mesenchymal architecture. To identify cell type-specific mechanisms and cell-cell interactions among the multiple lung resident cell types and inflammatory cells that contribute to COPD progression, we profiled 57,918 cells from lungs of COPD patients, non-COPD smokers, and never smokers using single-cell RNA sequencing technology. We predicted pseudotime of cell differentiation and cell-to-cell interaction networks in COPD. While epithelial components in never-smokers were relatively uniform, smoker groups represent extensive heterogeneity in epithelial cells, particularly in alveolar type 2 (AT2) clusters. Among AT2 cells, which are generally regarded as alveolar progenitors, we identified a unique subset that increased in COPD patients, and specifically expressed a series of chemokines including CXCL1 and CXCL8. A trajectory analysis revealed that the inflammatory AT2 cell subpopulation followed a unique differentiation path, and a prediction model of cell-to-cell interactions inferred significantly increased intercellular networks of inflammatory AT2 cells. Our results identify previously unidentified cell subsets and provide an insight into the biological and clinical characteristics of COPD pathogenesis.", "classifications": [ { "id": "Okamoto", "label": "Group Okamoto", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Naoaki", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Yu", "last_name": "Fujita", "name": null }, { "creator_type": "author", "first_name": "Jun", "last_name": "Nakayama", "name": null }, { "creator_type": "author", "first_name": "Yutaro", "last_name": "Mori", "name": null }, { "creator_type": "author", "first_name": "Tsukasa", "last_name": "Kadota", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Hayashi", "name": null }, { "creator_type": "author", "first_name": "Iwao", "last_name": "Shimomura", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Ohtsuka", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Okamoto", "name": null }, { "creator_type": "author", "first_name": "Jun", "last_name": "Araya", "name": null }, { "creator_type": "author", "first_name": "Kazuyoshi", "last_name": "Kuwano", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Yamamoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1165/rcmb.2021-0555oc" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "36108172" } }, "mesh": [ { "descriptor": "Alveolar Epithelial Cells", "descriptor_ui": "D056809", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Epithelial Cells", "descriptor_ui": "D004847", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Lung", "descriptor_ui": "D008168", "major_topic": false }, { "descriptor": "Pulmonary Disease, Chronic Obstructive", "descriptor_ui": "D029424", "major_topic": true } ], "publication": { "conference_name": null, "date": "2022 Sep 15", "date_precision": "day", "issue": "", "normalized_date": "2022-09-15", "pages": "", "proceedings_title": null, "publisher": "", "title": "American journal of respiratory cell and molecular biology", "volume": "", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Anomalous Epithelial Variations and Ectopic Inflammatory Response in Chronic Obstructive Pulmonary Disease.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Triple-negative essential thrombocythemia (ET) is a condition in which mutations in JAK2, CALR and MPL are all negative. Transformation to acute myeloid leukemia may occur during the course of ET, while B-acute lymphoblastic leukemia (B-ALL) is rare. We experienced a case diagnosed as B-ALL during the course of triple-negative ET. Notably, cytoreduction was required for the excessive increase in blood cells during the bone marrow recovery period after chemotherapies. Whole-exome sequencing identified 17 somatic mutations: 9 were identified in both ET and B-ALL samples, while 8 were specific to B-ALL, suggesting that these 8 might have caused the transformation.", "classifications": [ { "id": "Nishikii", "label": "Group Nishikii", "parent": "Shintaku", "type": "group" }, { "id": "Shintaku", "label": "Team Shintaku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yuri", "last_name": "Tsuboi", "name": null }, { "creator_type": "author", "first_name": "Tatsuhiro", "last_name": "Sakamoto", "name": null }, { "creator_type": "author", "first_name": "Kenichi", "last_name": "Makishima", "name": null }, { "creator_type": "author", "first_name": "Yasuhito", "last_name": "Suehara", "name": null }, { "creator_type": "author", "first_name": "Keiichiro", "last_name": "Hattori", "name": null }, { "creator_type": "author", "first_name": "Naoki", "last_name": "Kurita", "name": null }, { "creator_type": "author", "first_name": "Yasuhisa", "last_name": "Yokoyama", "name": null }, { "creator_type": "author", "first_name": "Takayasu", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Hidekazu", "last_name": "Nishikii", "name": null }, { "creator_type": "author", "first_name": "Naoshi", "last_name": "Obara", "name": null }, { "creator_type": "author", "first_name": "Fumiaki", "last_name": "Matsumura", "name": null }, { "creator_type": "author", "first_name": "Ryota", "last_name": "Matsuoka", "name": null }, { "creator_type": "author", "first_name": "Shigeru", "last_name": "Chiba", "name": null }, { "creator_type": "author", "first_name": "Mamiko", "last_name": "Sakata-Yanagimoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.2169/internalmedicine.0269-22" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "36104197" } }, "mesh": [ { "descriptor": "Calreticulin", "descriptor_ui": "D037282", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Janus Kinase 2", "descriptor_ui": "D053614", "major_topic": false }, { "descriptor": "Leukemia, Myeloid, Acute", "descriptor_ui": "D015470", "major_topic": true }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": false }, { "descriptor": "Precursor Cell Lymphoblastic Leukemia-Lymphoma", "descriptor_ui": "D054198", "major_topic": true }, { "descriptor": "Thrombocythemia, Essential", "descriptor_ui": "D013920", "major_topic": true } ], "publication": { "conference_name": null, "date": "2022 Sep 13", "date_precision": "day", "issue": "", "normalized_date": "2022-09-13", "pages": "", "proceedings_title": null, "publisher": "", "title": "Internal medicine (Tokyo, Japan)", "volume": "", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Triple-negative Thrombocythemia and Subsequent Acute Lymphoblastic Leukemia with Additional Somatic Mutations.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Pulsatile release of the hormone oxytocin (OT) mediates uterine contraction during parturition and milk ejection during lactation.(1-3) These pulses are generated by the unique activity patterns of the central neuroendocrine OT neurons located in the paraventricular and supraoptic hypothalamus. Classical studies have characterized putative OT neurons by in vivo extracellular recording techniques in rats and rabbits.(1)(,)(4-10) Due to technical limitations, however, the identity of OT neurons in these previous studies was speculative based on their electrophysiological characteristics and axonal projection to the posterior pituitary, not on OT gene expression. To pinpoint OT neural activities among other hypothalamic neurons that project to the pituitary(11)(,)(12) and make better use of cell-type-specific neuroscience toolkits,(13) a mouse model needs to be developed for the studies of parturition and lactation. We herein introduce viral genetic approaches in mice to characterize the maternal activities of OT neurons by fiber photometry. A sharp photometric peak of OT neurons appeared at approximately 520 s following simultaneous suckling stimuli from three pups. The amplitude of the peaks increased as the mother mice experienced lactation, irrespective of the age of the pups, suggesting the intrinsic plasticity of maternal OT neurons. Based on a mono-synaptic input map to OT neurons, we pharmacogenetically activated the inhibitory neurons in the bed nucleus of the stria terminalis and found the suppression of the activities of OT neurons. Collectively, our study illuminates temporal dynamics in the maternal neural activities of OT neurons and identifies one of its modulatory inputs.", "classifications": [ { "id": "Miyamichi", "label": "Group Miyamichi", "parent": "Enomoto", "type": "group" }, { "id": "Enomoto", "label": "Team Enomoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Hiroko", "last_name": "Yukinaga", "name": null }, { "creator_type": "author", "first_name": "Mitsue", "last_name": "Hagihara", "name": null }, { "creator_type": "author", "first_name": "Kazuko", "last_name": "Tsujimoto", "name": null }, { "creator_type": "author", "first_name": "Hsiao-Ling", "last_name": "Chiang", "name": null }, { "creator_type": "author", "first_name": "Shigeki", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Kazuto", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Kazunari", "last_name": "Miyamichi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.cub.2022.06.083" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "35868323" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Hypothalamus", "descriptor_ui": "D007031", "major_topic": false }, { "descriptor": "Lactation", "descriptor_ui": "D007774", "major_topic": true }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Oxytocin", "descriptor_ui": "D010121", "major_topic": true }, { "descriptor": "Paraventricular Hypothalamic Nucleus", "descriptor_ui": "D010286", "major_topic": false }, { "descriptor": "Pregnancy", "descriptor_ui": "D011247", "major_topic": false }, { "descriptor": "Thalamus", "descriptor_ui": "D013788", "major_topic": false } ], "publication": { "conference_name": null, "date": "2022 Sep 12", "date_precision": "day", "issue": "17", "normalized_date": "2022-09-12", "pages": "3821-3829.e6", "proceedings_title": null, "publisher": "", "title": "Current biology : CB", "volume": "32", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Recording and manipulation of the maternal oxytocin neural activities in mice.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "SUMMARY: High-throughput chromosome conformation capture (Hi-C) is a widely used assay for studying the three-dimensional (3D) genome organization across the whole genome. Here, we present PHi-C2, a Python package supported by mathematical and biophysical polymer modeling that converts input Hi-C matrix data into the polymer model's dynamics, structural conformations, and rheological features. The updated optimization algorithm for regenerating a highly similar Hi-C matrix provides a fast and accurate optimal solution compared to the previous version by eliminating the factors underlying the inefficiency of the optimization algorithm in the iterative optimization process. In addition, we have enabled a Google Colab workflow to run the algorithm, wherein users can easily change the parameters and check the results in the notebook. Overall, PHi-C2 represents a valuable tool for mining the dynamic 3D genome state embedded in Hi-C data. AVAILABILITY AND IMPLEMENTATION: PHi-C2 as the phic Python package is freely available under the GPL license and can be installed from the Python package index. The source code is available from GitHub at https://github.com/soyashinkai/PHi-C2. Moreover, users do not have to prepare a Python environment because PHi-C2 can run on Google Colab (https://bit.ly/3rlptGI). SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.", "classifications": [ { "id": "Onami", "label": "Group Onami", "parent": "Fujiwara", "type": "group" }, { "id": "Fujiwara", "label": "Team Fujiwara", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Soya", "last_name": "Shinkai", "name": null }, { "creator_type": "author", "first_name": "Hiroya", "last_name": "Itoga", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Kyoda", "name": null }, { "creator_type": "author", "first_name": "Shuichi", "last_name": "Onami", "name": null } ], "identifiers": { "doi": { "normalized": "10.1093/bioinformatics/btac613" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "36087002" } }, "mesh": [ { "descriptor": "Chromosomes", "descriptor_ui": "D002875", "major_topic": false }, { "descriptor": "Genome", "descriptor_ui": "D016678", "major_topic": true }, { "descriptor": "Molecular Conformation", "descriptor_ui": "D008968", "major_topic": false }, { "descriptor": "Polymers", "descriptor_ui": "D011108", "major_topic": false }, { "descriptor": "Software", "descriptor_ui": "D012984", "major_topic": true } ], "publication": { "conference_name": null, "date": "2022 Sep 10", "date_precision": "day", "issue": "", "normalized_date": "2022-09-10", "pages": "btac613", "proceedings_title": null, "publisher": "", "title": "Bioinformatics (Oxford, England)", "volume": "", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "PHi-C2: interpreting Hi-C data as the dynamic 3D genome state.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Low body temperature predicts a poor outcome in patients with heart failure, but the underlying pathological mechanisms and implications are largely unknown. Brown adipose tissue (BAT) was initially characterised as a thermogenic organ, and recent studies have suggested it plays a crucial role in maintaining systemic metabolic health. While these reports suggest a potential link between BAT and heart failure, the potential role of BAT dysfunction in heart failure has not been investigated. Here, we demonstrate that alteration of BAT function contributes to development of heart failure through disorientation in choline metabolism. Thoracic aortic constriction (TAC) or myocardial infarction (MI) reduced the thermogenic capacity of BAT in mice, leading to significant reduction of body temperature with cold exposure. BAT became hypoxic with TAC or MI, and hypoxic stress induced apoptosis of brown adipocytes. Enhancement of BAT function improved thermogenesis and cardiac function in TAC mice. Conversely, systolic function was impaired in a mouse model of genetic BAT dysfunction, in association with a low survival rate after TAC. Metabolomic analysis showed that reduced BAT thermogenesis was associated with elevation of plasma trimethylamine N-oxide (TMAO) levels. Administration of TMAO to mice led to significant reduction of phosphocreatine and ATP levels in cardiac tissue via suppression of mitochondrial complex IV activity. Genetic or pharmacological inhibition of flavin-containing monooxygenase reduced the plasma TMAO level in mice, and improved cardiac dysfunction in animals with left ventricular pressure overload. In patients with dilated cardiomyopathy, body temperature was low along with elevation of plasma choline and TMAO levels. These results suggest that maintenance of BAT homeostasis and reducing TMAO production could be potential next-generation therapies for heart failure.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yohko", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Ippei", "last_name": "Shimizu", "name": null }, { "creator_type": "author", "first_name": "Atsuhiro", "last_name": "Shimada", "name": null }, { "creator_type": "author", "first_name": "Keita", "last_name": "Nakahara", "name": null }, { "creator_type": "author", "first_name": "Sachiko", "last_name": "Yanagisawa", "name": null }, { "creator_type": "author", "first_name": "Minoru", "last_name": "Kubo", "name": null }, { "creator_type": "author", "first_name": "Shinji", "last_name": "Fukuda", "name": null }, { "creator_type": "author", "first_name": "Chiharu", "last_name": "Ishii", "name": null }, { "creator_type": "author", "first_name": "Hiromitsu", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Takamasa", "last_name": "Ishikawa", "name": null }, { "creator_type": "author", "first_name": "Kuniyuki", "last_name": "Kano", "name": null }, { "creator_type": "author", "first_name": "Junken", "last_name": "Aoki", "name": null }, { "creator_type": "author", "first_name": "Goro", "last_name": "Katsuumi", "name": null }, { "creator_type": "author", "first_name": "Masayoshi", "last_name": "Suda", "name": null }, { "creator_type": "author", "first_name": "Kazuyuki", "last_name": "Ozaki", "name": null }, { "creator_type": "author", "first_name": "Yutaka", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Shujiro", "last_name": "Okuda", "name": null }, { "creator_type": "author", "first_name": "Shigeo", "last_name": "Ohta", "name": null }, { "creator_type": "author", "first_name": "Shiki", "last_name": "Okamoto", "name": null }, { "creator_type": "author", "first_name": "Yasuhiko", "last_name": "Minokoshi", "name": null }, { "creator_type": "author", "first_name": "Kanako", "last_name": "Oda", "name": null }, { "creator_type": "author", "first_name": "Toshikuni", "last_name": "Sasaoka", "name": null }, { "creator_type": "author", "first_name": "Manabu", "last_name": "Abe", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Sakimura", "name": null }, { "creator_type": "author", "first_name": "Yoshiaki", "last_name": "Kubota", "name": null }, { "creator_type": "author", "first_name": "Norihiko", "last_name": "Yoshimura", "name": null }, { "creator_type": "author", "first_name": "Shingo", "last_name": "Kajimura", "name": null }, { "creator_type": "author", "first_name": "Maria", "last_name": "Zuriaga", "name": null }, { "creator_type": "author", "first_name": "Kenneth", "last_name": "Walsh", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Tohru", "last_name": "Minamino", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41598-022-19245-x" }, "pmcid": { "normalized": "PMC9436957" }, "pmid": { "normalized": "36050466" } }, "mesh": [ { "descriptor": "Adipocytes, Brown", "descriptor_ui": "D052437", "major_topic": false }, { "descriptor": "Adipose Tissue, Brown", "descriptor_ui": "D002001", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Choline", "descriptor_ui": "D002794", "major_topic": false }, { "descriptor": "Heart Failure", "descriptor_ui": "D006333", "major_topic": true }, { "descriptor": "Methylamines", "descriptor_ui": "D008744", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Myocardial Infarction", "descriptor_ui": "D009203", "major_topic": true }, { "descriptor": "Thermogenesis", "descriptor_ui": "D022722", "major_topic": false } ], "publication": { "conference_name": null, "date": "2022 Sep 1", "date_precision": "day", "issue": "1", "normalized_date": "2022-09-01", "pages": "14883", "proceedings_title": null, "publisher": "", "title": "Scientific reports", "volume": "12", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Brown adipose tissue dysfunction promotes heart failure via a trimethylamine N-oxide-dependent mechanism.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Computational fluid dynamics is widely used to simulate droplet-spreading behavior due to respiratory events. However, droplet generation inside the body, such as the number, mass, and particle size distribution, has not been quantitatively analyzed. The aim of this study was to identify quantitative characteristics of droplet generation during coughing. Airflow simulations were performed by coupling the discrete phase model and Eulerian wall film model to reproduce shear-induced stripping of airway mucosa. An ideal airway model with symmetric bifurcations was constructed, and the wall domain was covered by a mucous liquid film. The results of the transient airflow simulation indicated that the droplets had a wide particle size distribution of 0.1-400 microm, and smaller droplets were generated in larger numbers. In addition, the total mass and number of droplets generated increased with an increasing airflow. The total mass of the droplets also increased with an increasing mucous viscosity, and the largest number and size of droplets were obtained at a viscosity of 8 mPa s. The simulation methods used in this study can be used to quantify the particle size distribution and maximum particle diameter under various conditions.", "classifications": [ { "id": "Akaike", "label": "Group Akaike", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Hitomi", "last_name": "Anzai", "name": null }, { "creator_type": "author", "first_name": "Yugo", "last_name": "Shindo", "name": null }, { "creator_type": "author", "first_name": "Yutaro", "last_name": "Kohata", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Hasegawa", "name": null }, { "creator_type": "author", "first_name": "Hidemasa", "last_name": "Takana", "name": null }, { "creator_type": "author", "first_name": "Tetsuro", "last_name": "Matsunaga", "name": null }, { "creator_type": "author", "first_name": "Takaaki", "last_name": "Akaike", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Ohta", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41598-022-18788-3" }, "pmcid": { "normalized": "PMC9434508" }, "pmid": { "normalized": "36050319" } }, "mesh": [ { "descriptor": "Computer Simulation", "descriptor_ui": "D003198", "major_topic": false }, { "descriptor": "Cough", "descriptor_ui": "D003371", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Hydrodynamics", "descriptor_ui": "D057446", "major_topic": false }, { "descriptor": "Respiratory Aerosols and Droplets", "descriptor_ui": "D000088343", "major_topic": true }, { "descriptor": "Respiratory System", "descriptor_ui": "D012137", "major_topic": false } ], "publication": { "conference_name": null, "date": "2022 Sep 1", "date_precision": "day", "issue": "1", "normalized_date": "2022-09-01", "pages": "14849", "proceedings_title": null, "publisher": "", "title": "Scientific reports", "volume": "12", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Coupled discrete phase model and Eulerian wall film model for numerical simulation of respiratory droplet generation during coughing.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Cancer-specific metabolic activities play a crucial role in the pathogenesis of human malignancies. To investigate human acute leukemia-specific metabolic properties, we comprehensively measured the cellular metabolites within the CD34+ fraction of normal hematopoietic stem progenitor cells (HSPCs), and primary human acute myelogenous leukemia (AML) and lymphoblastic leukemia (ALL) cells. Here we show that human leukemia addicts to the branched-chain amino acid (BCAA) metabolism to maintain their stemness, irrespective of myeloid or lymphoid types. Human primary acute leukemias had BCAA transporters for BCAA uptake, cellular BCAA, alpha-ketoglutarate (alpha-KG) and cytoplasmic BCAA transaminase-1 (BCAT1) at significantly higher levels than control HSPCs. Isotope-tracing experiments showed that in primary leukemia cells, BCAT1 actively catabolizes BCAA using alpha-KG into branched-chain alpha-ketoacids (BCKAs), whose metabolic processes provide leukemia cells with critical substrates for the TCA cycle and the non-essential amino acids synthesis, both of which reproduce alpha-KG to maintain its cellular level. In xenogeneic transplantation experiments, deprivation of BCAA from daily diet strongly inhibited expansion, engraftment and self-renewal of human acute leukemia cells. Inhibition of BCAA catabolism in primary AML or ALL cells specifically inactivates polycomb repressive complex 2 (PRC2) function, an epigenetic regulator for stem cell signatures, through inhibiting transcription of PRC components, such as zeste homolog 2 (EZH2) and embryonic ectoderm development (EED). Accordingly, BCAA catabolism plays an important role in maintenance of stemness in primary human AML and ALL, and molecules related to the BCAA metabolism pathway should be critical targets for acute leukemia treatment.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yoshikane", "last_name": "Kikushige", "name": null }, { "creator_type": "author", "first_name": "Toshihiro", "last_name": "Miyamoto", "name": null }, { "creator_type": "author", "first_name": "Yu", "last_name": "Kochi", "name": null }, { "creator_type": "author", "first_name": "Yuichiro", "last_name": "Semba", "name": null }, { "creator_type": "author", "first_name": "Maki", "last_name": "Ohishi", "name": null }, { "creator_type": "author", "first_name": "Hidetoshi", "last_name": "Irifune", "name": null }, { "creator_type": "author", "first_name": "Kiwamu", "last_name": "Hatakeyama", "name": null }, { "creator_type": "author", "first_name": "Yuya", "last_name": "Kunisaki", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Sugio", "name": null }, { "creator_type": "author", "first_name": "Teppei", "last_name": "Sakoda", "name": null }, { "creator_type": "author", "first_name": "Kohta", "last_name": "Miyawaki", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Koichi", "last_name": "Akashi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1182/bloodadvances.2022008242" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "36044390" } }, "mesh": [ { "descriptor": "Amino Acids, Branched-Chain", "descriptor_ui": "D000597", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Keto Acids", "descriptor_ui": "D007651", "major_topic": false }, { "descriptor": "Leukemia, Myeloid, Acute", "descriptor_ui": "D015470", "major_topic": true }, { "descriptor": "Polycomb Repressive Complex 2", "descriptor_ui": "D063151", "major_topic": false }, { "descriptor": "Transaminases", "descriptor_ui": "D000637", "major_topic": false } ], "publication": { "conference_name": null, "date": "2022 Aug 31", "date_precision": "day", "issue": "", "normalized_date": "2022-08-31", "pages": "bloodadvances.2022008242", "proceedings_title": null, "publisher": "", "title": "Blood advances", "volume": "", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Human acute leukemia utilizes branched-chain amino acid catabolism to maintain stemness through regulating PRC2 function.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Critical chain length that divides small molecule crystallization from macromolecular crystallization is an important index in macro-organic chemistry to predict chain-length dependent properties of oligomers and polymers. However, extensive research on crystallization behavior of individual oligomers has been inhibited by difficulties in their synthesis and crystallization. Here, we report on the determination of critical chain length of macromolecular crystallization for structurally flexible polyketones consisting of 3,3-dimethylpentane-2,4-dione. Discrete polyketone oligomers were synthesized via stepwise elongation up to 20-mer. Powder and single crystal X-ray diffraction showed that the critical chain length for polyketones existed at an unexpectedly short chain length, 5-mer. While shorter oligomers adopted unique conformations and packing structures in the solid state, higher oligomers longer than 4-mer produced helical conformations and similar crystal packing. The critical chain length helped with understanding the inexplicable changes in melting point in the shorter chain length region resulting from chain conformations and packing styles.", "classifications": [ { "id": "Hijikata", "label": "Group Hijikata", "parent": "Tsuchiya", "type": "group" }, { "id": "Tsuchiya", "label": "Team Tsuchiya", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yuki", "last_name": "Ide", "name": null }, { "creator_type": "author", "first_name": "Yumehiro", "last_name": "Manabe", "name": null }, { "creator_type": "author", "first_name": "Yuya", "last_name": "Inaba", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Kinoshita", "name": null }, { "creator_type": "author", "first_name": "Jenny", "last_name": "Pirillo", "name": null }, { "creator_type": "author", "first_name": "Yuh", "last_name": "Hijikata", "name": null }, { "creator_type": "author", "first_name": "Tomoki", "last_name": "Yoneda", "name": null }, { "creator_type": "author", "first_name": "Kilingaru I.", "last_name": "Shivakumar", "name": null }, { "creator_type": "author", "first_name": "Saki", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Asakawa", "name": null }, { "creator_type": "author", "first_name": "Yasuhide", "last_name": "Inokuma", "name": null } ], "identifiers": { "doi": { "normalized": "10.1039/d2sc03083g" }, "pmcid": { "normalized": "PMC9434099" }, "pmid": { "normalized": "36199636" } }, "mesh": [], "publication": { "conference_name": null, "date": "2022 Aug 31", "date_precision": "day", "issue": "34", "normalized_date": "2022-08-31", "pages": "9848-9854", "proceedings_title": null, "publisher": "", "title": "Chemical science", "volume": "13", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Determination of the critical chain length for macromolecular crystallization using structurally flexible polyketones.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Background and Purpose Capillary arterialization, characterized by the coverage of pre-existing or nascent capillary vessels with vascular smooth muscle cells (VSMCs), is critical for the development of collateral arterioles to improve post-ischaemic blood flow. We previously demonstrated that the inhibition of transient receptor potential 6 subfamily C, member 6 (TRPC6) channels facilitate contractile differentiation of VSMCs under ischaemic stress. We here investigated whether TRPC6 inhibition promotes post-ischaemic blood flow recovery through capillary arterialization in vivo. Experimental Approach Mice were subjected to hindlimb ischaemia by ligating left femoral artery. The recovery rate of peripheral blood flow was calculated by the ratio of ischaemic left leg to non-ischaemic right one. The number and diameter of blood vessels were analysed by immunohistochemistry. Expression and phosphorylation levels of TRPC6 proteins were determined by western blotting and immunohistochemistry. Key Results Although the post-ischaemic blood flow recovery is reportedly dependent on endothelium-dependent relaxing factors, systemic TRPC6 deletion significantly promoted blood flow recovery under the condition that nitric oxide or prostacyclin production were inhibited, accompanying capillary arterialization. Cilostazol, a clinically approved drug for peripheral arterial disease, facilitates blood flow recovery by inactivating TRPC6 via phosphorylation at Thr69 in VSMCs. Furthermore, inhibition of TRPC6 channel activity by pyrazole-2 (Pyr2; BTP2; YM-58483) promoted post-ischaemic blood flow recovery in Apolipoprotein E-knockout mice. Conclusion and Implications Suppression of TRPC6 channel activity in VSMCs could be a new strategy for the improvement of post-ischaemic peripheral blood circulation.", "classifications": [ { "id": "JPMJCR2024", "label": "JPMJCR2024", "researcher": "Motohiro Nishida", "type": "grant" }, { "id": "Nishida", "label": "Group Nishida", "parent": "Nishida", "type": "group" }, { "id": "Nishimura", "label": "Group Nishimura", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Takuro", "last_name": "Numaga-Tomita", "name": null }, { "creator_type": "author", "first_name": "Tsukasa", "last_name": "Shimauchi", "name": null }, { "creator_type": "author", "first_name": "Yuri", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Kazuhiro", "last_name": "Nishiyama", "name": null }, { "creator_type": "author", "first_name": "Akiyuki", "last_name": "Nishimura", "name": null }, { "creator_type": "author", "first_name": "Kosuke", "last_name": "Sakata", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Inada", "name": null }, { "creator_type": "author", "first_name": "Satomi", "last_name": "Kita", "name": null }, { "creator_type": "author", "first_name": "Takahiro", "last_name": "Iwamoto", "name": null }, { "creator_type": "author", "first_name": "Junichi", "last_name": "Nabekura", "name": null }, { "creator_type": "author", "first_name": "Lutz", "last_name": "Birnbaumer", "name": null }, { "creator_type": "author", "first_name": "Yasuo", "last_name": "Mori", "name": null }, { "creator_type": "author", "first_name": "Motohiro", "last_name": "Nishida", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/bph.15942" }, "pmcid": { "normalized": null }, "pmid": { "normalized": null } }, "mesh": [], "publication": { "conference_name": null, "date": "2022-08-29", "date_precision": "day", "issue": "n/a", "normalized_date": "2022-08-29", "pages": "", "proceedings_title": null, "publisher": "", "title": "British Journal of Pharmacology", "volume": "n/a", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Inhibition of transient receptor potential cation channel 6 promotes capillary arterialization during post-ischaemic blood flow recovery", "url": "https://onlinelibrary.wiley.com/doi/abs/10.1111/bph.15942", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Non-small cell lung cancer (NSCLC) is a heterogeneous disease, with many oncogenic driver mutations, including de novo mutations in the Mesenchymal Epithelial Transition (MET) gene (specifically in Exon 14 [ex14]), that lead to tumourigenesis. Acquired alterations in the MET gene, specifically MET amplification is also associated with the development of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) resistance in patients with EGFR-mutant NSCLC. Although MET has become an actionable biomarker with the availability of MET-specific inhibitors in selected countries, there is differential accessibility to diagnostic platforms and targeted therapies across countries in Asia-Pacific (APAC). The Asian Thoracic Oncology Research Group (ATORG), an interdisciplinary group of experts from Australia, Hong Kong, Japan, Korea, Mainland China, Malaysia, the Philippines, Singapore, Taiwan, Thailand and Vietnam, discussed testing for MET alterations and considerations for using MET-specific inhibitors at a consensus meeting in January 2022, and in subsequent offline consultation. Consensus recommendations are provided by the ATORG group to address the unmet need for standardised approaches to diagnosing MET alterations in NSCLC and for using these therapies. MET inhibitors may be considered for first-line or second or subsequent lines of treatment for patients with advanced and metastatic NSCLC harbouring MET ex14 skipping mutations; MET ex14 testing is preferred within multi-gene panels for detecting targetable driver mutations in NSCLC. For patients with EGFR-mutant NSCLC and MET amplification leading to EGFR TKI resistance, enrolment in combination trials of EGFR TKIs and MET inhibitors is encouraged.", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Myung-Ju", "last_name": "Ahn", "name": null }, { "creator_type": "author", "first_name": "Marvin Jonne L.", "last_name": "Mendoza", "name": null }, { "creator_type": "author", "first_name": "Nick", "last_name": "Pavlakis", "name": null }, { "creator_type": "author", "first_name": "Terufumi", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Ross A.", "last_name": "Soo", "name": null }, { "creator_type": "author", "first_name": "Dong-Wan", "last_name": "Kim", "name": null }, { "creator_type": "author", "first_name": "Chong Kin", "last_name": "Liam", "name": null }, { "creator_type": "author", "first_name": "Te-Chun", "last_name": "Hsia", "name": null }, { "creator_type": "author", "first_name": "Chee Khoon", "last_name": "Lee", "name": null }, { "creator_type": "author", "first_name": "Thanyanan", "last_name": "Reungwetwattana", "name": null }, { "creator_type": "author", "first_name": "Sarayut", "last_name": "Geater", "name": null }, { "creator_type": "author", "first_name": "Oscar Siu Hong", "last_name": "Chan", "name": null }, { "creator_type": "author", "first_name": "Naiyarat", "last_name": "Prasongsook", "name": null }, { "creator_type": "author", "first_name": "Benjamin J.", "last_name": "Solomon", "name": null }, { "creator_type": "author", "first_name": "Thi Thai Hoa", "last_name": "Nguyen", "name": null }, { "creator_type": "author", "first_name": "Toshiyuki", "last_name": "Kozuki", "name": null }, { "creator_type": "author", "first_name": "James Chih-Hsin", "last_name": "Yang", "name": null }, { "creator_type": "author", "first_name": "Yi-Long", "last_name": "Wu", "name": null }, { "creator_type": "author", "first_name": "Tony Shu Kam", "last_name": "Mok", "name": null }, { "creator_type": "author", "first_name": "Daniel Shao-Weng", "last_name": "Tan", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.cllc.2022.07.012" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "36151006" } }, "mesh": [ { "descriptor": "Carcinoma, Non-Small-Cell Lung", "descriptor_ui": "D002289", "major_topic": true }, { "descriptor": "Drug Resistance, Neoplasm", "descriptor_ui": "D019008", "major_topic": false }, { "descriptor": "Epithelial-Mesenchymal Transition", "descriptor_ui": "D058750", "major_topic": true }, { "descriptor": "ErbB Receptors", "descriptor_ui": "D066246", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Lung Neoplasms", "descriptor_ui": "D008175", "major_topic": true }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": false }, { "descriptor": "Protein Kinase Inhibitors", "descriptor_ui": "D047428", "major_topic": false }, { "descriptor": "Proto-Oncogene Proteins c-met", "descriptor_ui": "D019859", "major_topic": false } ], "publication": { "conference_name": null, "date": "2022 Aug 23", "date_precision": "day", "issue": "", "normalized_date": "2022-08-23", "pages": "S1525-7304(22)00165-6", "proceedings_title": null, "publisher": "", "title": "Clinical lung cancer", "volume": "", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Asian Thoracic Oncology Research Group (ATORG) Expert Consensus Statement on MET Alterations in NSCLC: Diagnostic and Therapeutic Considerations.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "OBJECTIVES: Comprehensive genomic profiling (CGP) has been approved in Japan since June 2019, enabling mutation-specific therapy. Although tissue sampling via endoscopic ultrasound-guided tissue acquisition (EUS-TA) is standard in pancreatic cancer, reports on obtaining appropriate samples for CGP, especially for the OncoGuide NCC Oncopanel System (NOP) and FoundationOne CDx (FOne), are lacking. Therefore, we investigated the success rate and factors related to appropriate EUS-TA sampling for CGP analysis suitability in unresectable pancreatic ductal adenocarcinoma (UR-PDAC). METHODS: Participants comprised 150 UR-PDAC patients who underwent EUS-TA and tumor sample evaluation for CGP analysis suitability between June 2019 and December 2021. The proportion of patients meeting the criteria was evaluated considering tumor size, puncture lesion, presence of metastasis, type and size of puncture needle, suction method, number of punctures, and puncture route. RESULTS: In total, 39.2% (60/153) of samples met NOP analysis suitability criteria and 0% met FOne analysis suitability criteria. The suitability rate was significantly higher with 19G fine-needle biopsy (FNB) (56.0%; 42/75) than with 22G FNB (32.6%; 14/43) and 22G fine-needle aspiration (11.4%; 4/35). Nineteen-gauge needle (odds ratio [OR] 2.53; 95% confidence interval [CI] 1.15-5.57; P = 0.021) and FNB (OR 3.57; 95% CI 1.05-12.20; P = 0.041) were independent factors contributing to NOP analysis suitability. Among 30 patients who underwent actual NOP analysis, the analysis success rate was 100% (30/30). CONCLUSION: In sample collection via EUS-TA, 19G and FNB needles contribute to NOP analysis suitability.", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Go", "last_name": "Ikeda", "name": null }, { "creator_type": "author", "first_name": "Susumu", "last_name": "Hijioka", "name": null }, { "creator_type": "author", "first_name": "Yoshikuni", "last_name": "Nagashio", "name": null }, { "creator_type": "author", "first_name": "Yuta", "last_name": "Maruki", "name": null }, { "creator_type": "author", "first_name": "Akihiro", "last_name": "Ohba", "name": null }, { "creator_type": "author", "first_name": "Yuya", "last_name": "Hisada", "name": null }, { "creator_type": "author", "first_name": "Motohiro", "last_name": "Yoshinari", "name": null }, { "creator_type": "author", "first_name": "Shota", "last_name": "Harai", "name": null }, { "creator_type": "author", "first_name": "Hidetoshi", "last_name": "Kitamura", "name": null }, { "creator_type": "author", "first_name": "Takehiko", "last_name": "Koga", "name": null }, { "creator_type": "author", "first_name": "Yumi", "last_name": "Murashima", "name": null }, { "creator_type": "author", "first_name": "Kosuke", "last_name": "Maehara", "name": null }, { "creator_type": "author", "first_name": "Mao", "last_name": "Okada", "name": null }, { "creator_type": "author", "first_name": "Daiki", "last_name": "Yamashige", "name": null }, { "creator_type": "author", "first_name": "Kohei", "last_name": "Okamoto", "name": null }, { "creator_type": "author", "first_name": "Hidenobu", "last_name": "Hara", "name": null }, { "creator_type": "author", "first_name": "Yuya", "last_name": "Hagiwara", "name": null }, { "creator_type": "author", "first_name": "Daiki", "last_name": "Agarie", "name": null }, { "creator_type": "author", "first_name": "Tetsuro", "last_name": "Takasaki", "name": null }, { "creator_type": "author", "first_name": "Kotaro", "last_name": "Takeshita", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Kawasaki", "name": null }, { "creator_type": "author", "first_name": "Shunsuke", "last_name": "Kondo", "name": null }, { "creator_type": "author", "first_name": "Chigusa", "last_name": "Morizane", "name": null }, { "creator_type": "author", "first_name": "Hideki", "last_name": "Ueno", "name": null }, { "creator_type": "author", "first_name": "Nobuyoshi", "last_name": "Hiraoka", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null }, { "creator_type": "author", "first_name": "Yutaka", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Katsuhiko", "last_name": "Iwakiri", "name": null }, { "creator_type": "author", "first_name": "Takuji", "last_name": "Okusaka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/den.14423" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "35993898" } }, "mesh": [ { "descriptor": "Adenocarcinoma", "descriptor_ui": "D000230", "major_topic": true }, { "descriptor": "Endoscopic Ultrasound-Guided Fine Needle Aspiration", "descriptor_ui": "D061765", "major_topic": false }, { "descriptor": "Genomics", "descriptor_ui": "D023281", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Pancreas", "descriptor_ui": "D010179", "major_topic": false }, { "descriptor": "Pancreatic Neoplasms", "descriptor_ui": "D010190", "major_topic": true } ], "publication": { "conference_name": null, "date": "2022 Aug 22", "date_precision": "day", "issue": "", "normalized_date": "2022-08-22", "pages": "", "proceedings_title": null, "publisher": "", "title": "Digestive endoscopy : official journal of the Japan Gastroenterological Endoscopy Society", "volume": "", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Fine-needle biopsy with 19G needle is effective in combination with endoscopic ultrasound-guided tissue acquisition for genomic profiling of unresectable pancreatic cancer.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Although investigating drug modulation of cytochrome P450 (CYP) activity under physiological conditions is crucial in drug development to avoid severe adverse drug reactions, the current evaluation approaches that rely on the destructive and end-point analysis can be misleading due to invasive treatments and cellular heterogeneity. Here, we propose a non-destructive and high-content method for visualizing and quantifying intracellular CYP activity under drug administration by Raman microscopy. The redox-state and spin-state sensitive Raman measurement indicated that the induced CYPs in living hepatocytes were in oxidized and low-spin state, which is related to monooxygenase function of CYP. Moreover, glycogen depletion associated with CYP induction was simultaneously observed, indicating a relevant effect on glucose metabolism. By deciphering the overall changes in the biochemical fingerprints of hepatocytes, Raman microscopy offers a non-destructive and quantitative chemical imaging method to evaluate CYP activity at the single-cell level with the potential to facilitate future drug development schemes.", "classifications": [ { "id": "JPMJCR1925", "label": "JPMJCR1925", "researcher": "Katsumasa Fujita", "type": "grant" }, { "id": "Fujita", "label": "Group Fujita", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Menglu", "last_name": "Li", "name": null }, { "creator_type": "author", "first_name": "Yasunori", "last_name": "Nawa", "name": null }, { "creator_type": "author", "first_name": "Seiichi", "last_name": "Ishida", "name": null }, { "creator_type": "author", "first_name": "Yasunari", "last_name": "Kanda", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Fujita", "name": null }, { "creator_type": "author", "first_name": "Katsumasa", "last_name": "Fujita", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s42003-022-03713-1" }, "pmcid": { "normalized": "PMC9395422" }, "pmid": { "normalized": "35995965" } }, "mesh": [ { "descriptor": "Cytochrome P-450 Enzyme System", "descriptor_ui": "D003577", "major_topic": true }, { "descriptor": "Enzyme Induction", "descriptor_ui": "D004790", "major_topic": false }, { "descriptor": "Hepatocytes", "descriptor_ui": "D022781", "major_topic": false }, { "descriptor": "Microscopy", "descriptor_ui": "D008853", "major_topic": true } ], "publication": { "conference_name": null, "date": "2022 Aug 22", "date_precision": "day", "issue": "1", "normalized_date": "2022-08-22", "pages": "778", "proceedings_title": null, "publisher": "", "title": "Communications biology", "volume": "5", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Label-free chemical imaging of cytochrome P450 activity by Raman microscopy.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Abnormal/cancerous cells within healthy epithelial tissues undergo apical extrusion to protect against carcinogenesis, although they acquire invasive capacity once carcinogenesis progresses. However, the molecular mechanisms by which cancer cells escape from apical extrusion and invade surrounding tissues remain elusive. In this study, we demonstrate a molecular mechanism for cell fate switching during epithelial cell competition. We found that during competition within epithelial cell layers, Src transformation promotes maturation of focal adhesions and degradation of extracellular matrix. Src-transformed cells underwent basal delamination by Src activation within sphingolipid/cholesterol-enriched membrane microdomains/lipid rafts, whereas they were apically extruded when Src was outside of lipid rafts. A comparative analysis of contrasting phenotypes revealed that activation of the Src-STAT3-MMP axis through lipid rafts was required for basal delamination. CUB-domain-containing protein 1 (CDCP1) was identified as an Src-activating scaffold and as a Met regulator in lipid rafts, and its overexpression induced basal delamination. In renal cancer models, CDCP1 promoted epithelial-mesenchymal transition-mediated invasive behavior by activating the Src-STAT3-MMP axis through Met activation. Overall, these results suggest that spatial activation of Src signaling in lipid rafts confers resistance to apical extrusion and invasive potential on epithelial cells to promote carcinogenesis.", "classifications": [ { "id": "Okuda", "label": "Group Okuda", "parent": "Imayoshi", "type": "group" }, { "id": "Imayoshi", "label": "Team Imayoshi", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Kentaro", "last_name": "Kajiwara", "name": null }, { "creator_type": "author", "first_name": "Ping-Kuan", "last_name": "Chen", "name": null }, { "creator_type": "author", "first_name": "Yuichi", "last_name": "Abe", "name": null }, { "creator_type": "author", "first_name": "Satoru", "last_name": "Okuda", "name": null }, { "creator_type": "author", "first_name": "Shunsuke", "last_name": "Kon", "name": null }, { "creator_type": "author", "first_name": "Jun", "last_name": "Adachi", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Tomonaga", "name": null }, { "creator_type": "author", "first_name": "Yasuyuki", "last_name": "Fujita", "name": null }, { "creator_type": "author", "first_name": "Masato", "last_name": "Okada", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.cub.2022.06.038" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "35809567" } }, "mesh": [ { "descriptor": "Antigens, Neoplasm", "descriptor_ui": "D000951", "major_topic": false }, { "descriptor": "Carcinogenesis", "descriptor_ui": "D063646", "major_topic": false }, { "descriptor": "Cell Adhesion Molecules", "descriptor_ui": "D015815", "major_topic": false }, { "descriptor": "Cell Competition", "descriptor_ui": "D000084502", "major_topic": true }, { "descriptor": "Epithelial Cells", "descriptor_ui": "D004847", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Membrane Microdomains", "descriptor_ui": "D021962", "major_topic": true }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false } ], "publication": { "conference_name": null, "date": "2022 Aug 22", "date_precision": "day", "issue": "16", "normalized_date": "2022-08-22", "pages": "3460-3476.e6", "proceedings_title": null, "publisher": "", "title": "Current biology : CB", "volume": "32", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Src activation in lipid rafts confers epithelial cells with invasive potential to escape from apical extrusion during cell competition.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Living cells actively deform and move by their force generations in three-dimensional (3D) space. These 3D cell dynamics occur over a long-term time scale, ranging from tens of minutes to days. On such a time scale, turnover of cell membrane constituents due to endocytosis and exocytosis cannot be ignored, i.e., the surface membrane dynamically deforms without mass conservation. Although membrane turnover is essential for large deformation of cells, there is no computational framework yet to simulate long-term cell dynamics with a non-conservative fluidic membrane. In this paper, we proposed a computational framework for simulating the long-term dynamics of a cell membrane in 3D space. For this purpose, in the proposed framework, the cell surface membrane is treated as a viscous fluid membrane without mass conservation. Cell shape is discretized by a triangular mesh, and its dynamics are expressed by effective energy and dissipation function. The mesh structure, distorted by membrane motion, is dynamically optimized by introducing a modified dynamic remeshing method. To validate the proposed framework, numerical simulations were performed, showing that the membrane flow is reproduced in a physically consistent manner and that the artificial effects of the remeshing method were negligible. To further demonstrate the applicability of the proposed framework, numerical simulations of cell migration induced by a mechanism similar to the Marangoni effect, i.e., the polarized surface tension actively generated by the cell, were performed. The observed cell behaviors agreed with existing analytical solutions, indicating that the proposed computational framework can quantitatively reproduce long-term active cell dynamics with membrane turnover. Based on the simple description of cell membrane dynamics, this framework provides a useful basis for analyzing various cell shaping and movement.", "classifications": [ { "id": "JPMJCR1921", "label": "JPMJCR1921", "researcher": "Itaru Imayoshi", "type": "grant" }, { "id": "Imayoshi", "label": "Group Imayoshi", "parent": "Imayoshi", "type": "group" }, { "id": "Imayoshi", "label": "Team Imayoshi", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Satoru", "last_name": "Okuda", "name": null }, { "creator_type": "author", "first_name": "Katsuhiko", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Tetsuya", "last_name": "Hiraiwa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1140/epje/s10189-022-00223-0" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "35984568" } }, "mesh": [ { "descriptor": "Cell Membrane", "descriptor_ui": "D002462", "major_topic": false }, { "descriptor": "Cell Shape", "descriptor_ui": "D048430", "major_topic": false }, { "descriptor": "Computer Simulation", "descriptor_ui": "D003198", "major_topic": false }, { "descriptor": "Metabolic Networks and Pathways", "descriptor_ui": "D053858", "major_topic": true }, { "descriptor": "Viscosity", "descriptor_ui": "D014783", "major_topic": false } ], "publication": { "conference_name": null, "date": "2022 Aug 19", "date_precision": "day", "issue": "8", "normalized_date": "2022-08-19", "pages": "69", "proceedings_title": null, "publisher": "", "title": "The European physical journal. E, Soft matter", "volume": "45", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Continuum modeling of non-conservative fluid membrane for simulating long-term cell dynamics.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "INTRODUCTION: This study explored the predictors of a histological aggressive component in ground glass opacity-containing lung adenocarcinoma. METHODS: Of the 2388 patients who underwent resection for lung cancer at our institute between 2017 and 2020, we collected data on the 501 patients with ground glass opacity-containing adenocarcinoma with a total diameter of 0.5 (P < 0.01), maximum standardized uptake value on positron emission tomography >/=1.5 (P = 0.01) and smoking index >20 pack-years (P = 0.01) were predictors of the presence of a histological aggressive component. A total of 98% of cases without any of the above factors did not have a histological aggressive component. CONCLUSIONS: Approximately 7% of ground glass opacity-containing small adenocarcinomas contained histological aggressive component. A consolidation/tumour ratio > 0.5, maximum standardized uptake value >/= 1.5 and smoking index >20 pack-years were predictors for such cases. These predictors may be useful for screening patients with a potentially high risk of a poor prognosis and for prioritizing resection without delay.", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Masaya", "last_name": "Yotsukura", "name": null }, { "creator_type": "author", "first_name": "Kazuo", "last_name": "Nakagawa", "name": null }, { "creator_type": "author", "first_name": "Chihiro", "last_name": "Takemura", "name": null }, { "creator_type": "author", "first_name": "Yukihiro", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Kimiteru", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Hirokazu", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Masahiko", "last_name": "Kusumoto", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null }, { "creator_type": "author", "first_name": "Shun-Ichi", "last_name": "Watanabe", "name": null } ], "identifiers": { "doi": { "normalized": "10.1093/jjco/hyac131" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "35975671" } }, "mesh": [ { "descriptor": "Adenocarcinoma", "descriptor_ui": "D000230", "major_topic": true }, { "descriptor": "Adenocarcinoma of Lung", "descriptor_ui": "D000077192", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Lung Neoplasms", "descriptor_ui": "D008175", "major_topic": true }, { "descriptor": "Neoplasm Staging", "descriptor_ui": "D009367", "major_topic": false }, { "descriptor": "Pneumonectomy", "descriptor_ui": "D011013", "major_topic": false }, { "descriptor": "Positron-Emission Tomography", "descriptor_ui": "D049268", "major_topic": false }, { "descriptor": "Prognosis", "descriptor_ui": "D011379", "major_topic": false }, { "descriptor": "Retrospective Studies", "descriptor_ui": "D012189", "major_topic": false } ], "publication": { "conference_name": null, "date": "2022 Aug 16", "date_precision": "day", "issue": "", "normalized_date": "2022-08-16", "pages": "hyac131", "proceedings_title": null, "publisher": "", "title": "Japanese journal of clinical oncology", "volume": "", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Aggressive histological component in subsolid lung adenocarcinoma: priority for resection without delay.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: Improved optical diagnostic technology is needed that can be used by also outside expert centers. Hence, we developed an artificial intelligence (AI) system that automatically and robustly predicts the pathological diagnosis based on the revised Vienna Classification using standard colonoscopy images. METHODS: We prepared deep learning algorithms and colonoscopy images containing pathologically proven lesions (56,872 images, 6775 lesions). Four classifications were adopted: revised Vienna Classification category 1, 3, and 4/5 and normal images. The best algorithm-ResNet152-in the independent internal validation (14,048 images, 1718 lesions) was used for external validation (255 images, 128 lesions) based on neoplastic and non-neoplastic classification. Diagnostic performance of endoscopists was compared using a computer-assisted interpreting test. RESULTS: In the internal validation, the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy for adenoma (category 3) of 84.6% (95% CI 83.5-85.6%), 99.7% (99.5-99.8%), 90.8% (89.9-91.7%), 89.2% (88.5-99.0%), and 89.8% (89.3-90.4%), respectively. In the external validation, ResNet152's sensitivity, specificity, PPV, NPV, and accuracy for neoplastic lesions were 88.3% (82.6-94.1%), 90.3% (83.0-97.7%), 94.6% (90.5-98.8%), 80.0% (70.6-89.4%), and 89.0% (84.5-93.6%), respectively. This diagnostic performance was superior to that of expert endoscopists. Area under the receiver-operating characteristic curve was 0.903 (0.860-0.946). CONCLUSIONS: The developed AI system can help non-expert endoscopists make differential diagnoses of colorectal neoplasia on par with expert endoscopists during colonoscopy. (229/250 words).", "classifications": [ { "id": "Hamamoto", "label": "Group Hamamoto", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Masayoshi", "last_name": "Yamada", "name": null }, { "creator_type": "author", "first_name": "Ryosaku", "last_name": "Shino", "name": null }, { "creator_type": "author", "first_name": "Hiroko", "last_name": "Kondo", "name": null }, { "creator_type": "author", "first_name": "Shigemi", "last_name": "Yamada", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Takamaru", "name": null }, { "creator_type": "author", "first_name": "Taku", "last_name": "Sakamoto", "name": null }, { "creator_type": "author", "first_name": "Pradeep", "last_name": "Bhandari", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Imaoka", "name": null }, { "creator_type": "author", "first_name": "Aya", "last_name": "Kuchiba", "name": null }, { "creator_type": "author", "first_name": "Taro", "last_name": "Shibata", "name": null }, { "creator_type": "author", "first_name": "Yutaka", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Ryuji", "last_name": "Hamamoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/s00535-022-01908-1" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "35972582" } }, "mesh": [ { "descriptor": "Adenoma", "descriptor_ui": "D000236", "major_topic": true }, { "descriptor": "Artificial Intelligence", "descriptor_ui": "D001185", "major_topic": false }, { "descriptor": "Colonoscopy", "descriptor_ui": "D003113", "major_topic": false }, { "descriptor": "Colorectal Neoplasms", "descriptor_ui": "D015179", "major_topic": true }, { "descriptor": "Deep Learning", "descriptor_ui": "D000077321", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false } ], "publication": { "conference_name": null, "date": "2022 Aug 16", "date_precision": "day", "issue": "", "normalized_date": "2022-08-16", "pages": "", "proceedings_title": null, "publisher": "", "title": "Journal of gastroenterology", "volume": "", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Robust automated prediction of the revised Vienna Classification in colonoscopy using deep learning: development and initial external validation.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Gastric foveolar-type adenoma (FA) is a rare benign neoplasm occurring either sporadically or in patients with familial adenomatous polyposis (FAP). However, the molecular features of FA and the relationship between sporadic and syndromic lesions remain unclear. In this study, we performed clinicopathological, immunohistochemical, and genetic analyses of 18 sporadic and 30 FAP-associated FAs. Most sporadic and FAP-associated FAs were located in the upper or middle third of the stomach, on a background of fundic gland mucosa. Most lesions were low-grade, but 3 lesions had a high-grade component. Sporadic FAs included 2 morphologically distinct subtypes, that is, flat and raspberry-like FAs, which we distinguished based on the endoscopic features. Seven lesions were regarded as flat FAs, appearing as large, slightly elevated lesions and measuring 11 to 87 mm in size. Conversely, 10 raspberry-like FAs were small bright-red polyps, measuring 2 to 8 mm in size. FAP-associated FAs, particularly larger lesions, exhibited morphologic features resembling flat FAs but varied significantly in size (2 to 103 mm). Mutation analysis identified APC and KRAS mutations in all flat FAs but never in raspberry-like FAs. Remarkably, somatic APC and KRAS mutations were also detected in 19 (63%) and 27 (90%) of FAP-associated FAs, respectively. This indicates that they are genetically equivalent to sporadic, flat FAs. This study showed that sporadic FA includes at least 2 morphologically and genetically distinct subtypes: flat and raspberry-like FA. Furthermore, flat FA represents a sporadic counterpart of FAP-associated FA.", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Tomoaki", "last_name": "Naka", "name": null }, { "creator_type": "author", "first_name": "Taiki", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Hourin", "last_name": "Cho", "name": null }, { "creator_type": "author", "first_name": "Noriko", "last_name": "Tanabe", "name": null }, { "creator_type": "author", "first_name": "Teruhiko", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null }, { "creator_type": "author", "first_name": "Takaki", "last_name": "Yoshikawa", "name": null }, { "creator_type": "author", "first_name": "Seiichiro", "last_name": "Abe", "name": null }, { "creator_type": "author", "first_name": "Shigeki", "last_name": "Sekine", "name": null } ], "identifiers": { "doi": { "normalized": "10.1097/pas.0000000000001949" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "35968980" } }, "mesh": [ { "descriptor": "Adenomatous Polyposis Coli", "descriptor_ui": "D011125", "major_topic": true }, { "descriptor": "Adenomatous Polyps", "descriptor_ui": "D018256", "major_topic": false }, { "descriptor": "DNA Mutational Analysis", "descriptor_ui": "D004252", "major_topic": false }, { "descriptor": "Gastric Mucosa", "descriptor_ui": "D005753", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Proto-Oncogene Proteins p21(ras)", "descriptor_ui": "D016283", "major_topic": false }, { "descriptor": "Stomach Neoplasms", "descriptor_ui": "D013274", "major_topic": true } ], "publication": { "conference_name": null, "date": "2022 Aug 15", "date_precision": "day", "issue": "", "normalized_date": "2022-08-15", "pages": "", "proceedings_title": null, "publisher": "", "title": "The American journal of surgical pathology", "volume": "", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Sporadic and Familial Adenomatous Polyposis-associated Foveolar-type Adenoma of the Stomach.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Metabolic regulation in skeletal muscle is essential for blood glucose homeostasis. Obesity causes insulin resistance in skeletal muscle, leading to hyperglycemia and type 2 diabetes. In this study, we performed multiomic analysis of the skeletal muscle of wild-type (WT) and leptin-deficient obese (ob/ob) mice, and constructed regulatory transomic networks for metabolism after oral glucose administration. Our network revealed that metabolic regulation by glucose-responsive metabolites had a major effect on WT mice, especially carbohydrate metabolic pathways. By contrast, in ob/ob mice, much of the metabolic regulation by glucose-responsive metabolites was lost and metabolic regulation by glucose-responsive genes was largely increased, especially in carbohydrate and lipid metabolic pathways. We present some characteristic metabolic regulatory pathways found in central carbon, branched amino acids, and ketone body metabolism. Our transomic analysis will provide insights into how skeletal muscle responds to changes in blood glucose and how it fails to respond in obesity.", "classifications": [ { "id": "JPMJCR2123", "label": "JPMJCR2123", "researcher": "Shinya Kuroda", "type": "grant" }, { "id": "Kuroda", "label": "Group Kuroda", "parent": "Kuroda", "type": "group" }, { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Toshiya", "last_name": "Kokaji", "name": null }, { "creator_type": "author", "first_name": "Miki", "last_name": "Eto", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Hatano", "name": null }, { "creator_type": "author", "first_name": "Katsuyuki", "last_name": "Yugi", "name": null }, { "creator_type": "author", "first_name": "Keigo", "last_name": "Morita", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Ohno", "name": null }, { "creator_type": "author", "first_name": "Masashi", "last_name": "Fujii", "name": null }, { "creator_type": "author", "first_name": "Ken-Ichi", "last_name": "Hironaka", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Riku", "last_name": "Egami", "name": null }, { "creator_type": "author", "first_name": "Saori", "last_name": "Uematsu", "name": null }, { "creator_type": "author", "first_name": "Akira", "last_name": "Terakawa", "name": null }, { "creator_type": "author", "first_name": "Yifei", "last_name": "Pan", "name": null }, { "creator_type": "author", "first_name": "Hideki", "last_name": "Maehara", "name": null }, { "creator_type": "author", "first_name": "Dongzi", "last_name": "Li", "name": null }, { "creator_type": "author", "first_name": "Yunfan", "last_name": "Bai", "name": null }, { "creator_type": "author", "first_name": "Takaho", "last_name": "Tsuchiya", "name": null }, { "creator_type": "author", "first_name": "Haruka", "last_name": "Ozaki", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Inoue", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Kubota", "name": null }, { "creator_type": "author", "first_name": "Yutaka", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Akiyoshi", "last_name": "Hirayama", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Kuroda", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41598-022-17964-9" }, "pmcid": { "normalized": "PMC9374747" }, "pmid": { "normalized": "35962137" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Blood Glucose", "descriptor_ui": "D001786", "major_topic": false }, { "descriptor": "Diabetes Mellitus, Type 2", "descriptor_ui": "D003924", "major_topic": true }, { "descriptor": "Glucose", "descriptor_ui": "D005947", "major_topic": false }, { "descriptor": "Insulin Resistance", "descriptor_ui": "D007333", "major_topic": true }, { "descriptor": "Leptin", "descriptor_ui": "D020738", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Obese", "descriptor_ui": "D008820", "major_topic": false }, { "descriptor": "Muscle, Skeletal", "descriptor_ui": "D018482", "major_topic": false }, { "descriptor": "Obesity", "descriptor_ui": "D009765", "major_topic": false } ], "publication": { "conference_name": null, "date": "2022 Aug 12", "date_precision": "day", "issue": "1", "normalized_date": "2022-08-12", "pages": "13719", "proceedings_title": null, "publisher": "", "title": "Scientific reports", "volume": "12", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "In vivo transomic analyses of glucose-responsive metabolism in skeletal muscle reveal core differences between the healthy and obese states.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "OBJECTIVE: We investigated the metabolic changes in pancreatic ductal adenocarcinoma to identify the mechanisms of treatment response of neoadjuvant chemoradiation therapy. METHODS: Frozen tumor and non-neoplastic pancreas tissues were prospectively obtained from 88 patients with pancreatic ductal adenocarcinoma who underwent curative-intent surgery. Sixty-two patients received neoadjuvant chemoradiation therapy and 26 patients did not receive neoadjuvant therapy (control group). Comprehensive analysis of metabolites in tumor and non-neoplastic pancreatic tissue was performed by capillary electrophoresis-mass spectrometry. RESULTS: Capillary electrophoresis-mass spectrometry detected 90 metabolites for analysis among more than 500 ionic metabolites quantified. There were significant differences in 27 tumor metabolites between the neoadjuvant chemoradiation therapy and control groups. There were significant differences in eight metabolites [1-MethylnNicotinamide, Carnitine, Glucose, Glutathione (red), N-acetylglucosamine 6-phosphate, N-acetylglucosamine 1-phosphate, UMP, Phosphocholine] between good responder and poor responder for neoadjuvant chemoradiation therapy. Among these metabolites, phosphocholine, Carnitine and Glutathione were associated with recurrence-free survival only in the neoadjuvant chemoradiation therapy group. Microarray confirmed marked gene suppression of choline transporters [CTL1-4 (SLC44A1-44A4)] in pancreatic ductal adenocarcinoma tissue of neoadjuvant chemoradiation therapy group. CONCLUSION: The present study identifies several important metabolic consequences and potential neoadjuvant chemoradiation therapy targets in pancreatic ductal adenocarcinoma. Choline metabolism is one of the key pathways involved in recurrence of the patients with pancreatic ductal adenocarcinoma who received neoadjuvant chemoradiation therapy.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yukiko", "last_name": "Wada", "name": null }, { "creator_type": "author", "first_name": "Keiichi", "last_name": "Okano", "name": null }, { "creator_type": "author", "first_name": "Kiyotoshi", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Sugimoto", "name": null }, { "creator_type": "author", "first_name": "Ayaka", "last_name": "Shimomura", "name": null }, { "creator_type": "author", "first_name": "Mina", "last_name": "Nagao", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Matsukawa", "name": null }, { "creator_type": "author", "first_name": "Yasuhisa", "last_name": "Ando", "name": null }, { "creator_type": "author", "first_name": "Hironobu", "last_name": "Suto", "name": null }, { "creator_type": "author", "first_name": "Minoru", "last_name": "Oshima", "name": null }, { "creator_type": "author", "first_name": "Akihiro", "last_name": "Kondo", "name": null }, { "creator_type": "author", "first_name": "Eisuke", "last_name": "Asano", "name": null }, { "creator_type": "author", "first_name": "Takayoshi", "last_name": "Kishino", "name": null }, { "creator_type": "author", "first_name": "Kensuke", "last_name": "Kumamoto", "name": null }, { "creator_type": "author", "first_name": "Hideki", "last_name": "Kobara", "name": null }, { "creator_type": "author", "first_name": "Hideki", "last_name": "Kamada", "name": null }, { "creator_type": "author", "first_name": "Tsutomu", "last_name": "Masaki", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Yasuyuki", "last_name": "Suzuki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1093/jjco/hyac074" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "35523689" } }, "mesh": [ { "descriptor": "Antigens, CD", "descriptor_ui": "D015703", "major_topic": false }, { "descriptor": "Carcinoma, Pancreatic Ductal", "descriptor_ui": "D021441", "major_topic": true }, { "descriptor": "Carnitine", "descriptor_ui": "D002331", "major_topic": false }, { "descriptor": "Chemoradiotherapy", "descriptor_ui": "D059248", "major_topic": false }, { "descriptor": "Glutathione", "descriptor_ui": "D005978", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Neoadjuvant Therapy", "descriptor_ui": "D020360", "major_topic": false }, { "descriptor": "Neoplasm Recurrence, Local", "descriptor_ui": "D009364", "major_topic": false }, { "descriptor": "Organic Cation Transport Proteins", "descriptor_ui": "D027701", "major_topic": false }, { "descriptor": "Pancreatectomy", "descriptor_ui": "D010180", "major_topic": false }, { "descriptor": "Pancreatic Neoplasms", "descriptor_ui": "D010190", "major_topic": true }, { "descriptor": "Phosphorylcholine", "descriptor_ui": "D010767", "major_topic": false } ], "publication": { "conference_name": null, "date": "2022 Aug 5", "date_precision": "day", "issue": "8", "normalized_date": "2022-08-05", "pages": "879-887", "proceedings_title": null, "publisher": "", "title": "Japanese journal of clinical oncology", "volume": "52", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Tumor metabolic alterations after neoadjuvant chemoradiotherapy predict postoperative recurrence in patients with pancreatic cancer.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The pheromonal information received by the vomeronasal system plays a crucial role in regulating social behaviors such as aggression in mice. Despite accumulating knowledge of the brain regions involved in aggression, the specific vomeronasal receptors and the exact neural circuits responsible for pheromone-mediated aggression remain unknown. Here, we identified one murine vomeronasal receptor, Vmn2r53, that is activated by urine from males of various strains and is responsible for evoking intermale aggression. We prepared a purified pheromonal fraction and Vmn2r53 knockout mice and applied genetic tools for neuronal activity recording, manipulation, and circuit tracing to decipher the neural mechanisms underlying Vmn2r53-mediated aggression. We found that Vmn2r53-mediated aggression is regulated by specific neuronal populations in the ventral premammillary nucleus and the ventromedial hypothalamic nucleus. Together, our results shed light on the hypothalamic regulation of male aggression mediated by a single vomeronasal receptor.", "classifications": [ { "id": "Miyamichi", "label": "Group Miyamichi", "parent": "Enomoto", "type": "group" }, { "id": "Enomoto", "label": "Team Enomoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Takumi", "last_name": "Itakura", "name": null }, { "creator_type": "author", "first_name": "Ken", "last_name": "Murata", "name": null }, { "creator_type": "author", "first_name": "Kazunari", "last_name": "Miyamichi", "name": null }, { "creator_type": "author", "first_name": "Kentaro K.", "last_name": "Ishii", "name": null }, { "creator_type": "author", "first_name": "Yoshihiro", "last_name": "Yoshihara", "name": null }, { "creator_type": "author", "first_name": "Kazushige", "last_name": "Touhara", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.neuron.2022.05.002" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "35654036" } }, "mesh": [ { "descriptor": "Aggression", "descriptor_ui": "D000374", "major_topic": true }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Hypothalamus", "descriptor_ui": "D007031", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Pheromones", "descriptor_ui": "D010675", "major_topic": false }, { "descriptor": "Ventromedial Hypothalamic Nucleus", "descriptor_ui": "D014697", "major_topic": false }, { "descriptor": "Vomeronasal Organ", "descriptor_ui": "D019147", "major_topic": true } ], "publication": { "conference_name": null, "date": "2022 Aug 3", "date_precision": "day", "issue": "15", "normalized_date": "2022-08-03", "pages": "2455-2469.e8", "proceedings_title": null, "publisher": "", "title": "Neuron", "volume": "110", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "A single vomeronasal receptor promotes intermale aggression through dedicated hypothalamic neurons.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Hematopoietic stem cells (HSCs) are produced from the blood vessel walls and circulate in the blood during the perinatal period. However, the migration dynamics of how HSCs enter the bone marrow remain elusive. To observe the dynamics of HSCs over time, the present study develops an intravital imaging method to visualize bone marrow in neonatal long bones formed by endochondral ossification which is essential for HSC niche formation. Endogenous HSCs are labeled with tdTomato under the control of an HSC marker gene Hlf, and a customized imaging system with a bone penetrating laser is developed for intravital imaging of tdTomato-labeled neonatal HSCs in undrilled tibia, which is essential to avoid bleeding from fragile neonatal tibia by bone drilling. The migration speed of neonatal HSCs is higher than that of adult HSCs. Neonatal HSCs migrate from outside to inside the tibia via the blood vessels that penetrate the bone, which is a transient structure during the neonatal period, and settle on the blood vessel wall in the bone marrow. The results obtained from direct observations in vivo reveal the motile dynamics and colonization process of neonatal HSCs during bone marrow formation.", "classifications": [ { "id": "Higaki", "label": "Group Higaki", "parent": "Ueda", "type": "group" }, { "id": "Ueda", "label": "Team Ueda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yuji", "last_name": "Takihara", "name": null }, { "creator_type": "author", "first_name": "Takumi", "last_name": "Higaki", "name": null }, { "creator_type": "author", "first_name": "Tomomasa", "last_name": "Yokomizo", "name": null }, { "creator_type": "author", "first_name": "Terumasa", "last_name": "Umemoto", "name": null }, { "creator_type": "author", "first_name": "Kazunori", "last_name": "Ariyoshi", "name": null }, { "creator_type": "author", "first_name": "Michihiro", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Maiko", "last_name": "Sezaki", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Takizawa", "name": null }, { "creator_type": "author", "first_name": "Toshihiro", "last_name": "Inoue", "name": null }, { "creator_type": "author", "first_name": "Toshio", "last_name": "Suda", "name": null }, { "creator_type": "author", "first_name": "Hidenobu", "last_name": "Mizuno", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s42003-022-03733-x" }, "pmcid": { "normalized": "PMC9346000" }, "pmid": { "normalized": "35918480" } }, "mesh": [ { "descriptor": "Bone and Bones", "descriptor_ui": "D001842", "major_topic": false }, { "descriptor": "Bone Marrow", "descriptor_ui": "D001853", "major_topic": true }, { "descriptor": "Diagnostic Imaging", "descriptor_ui": "D003952", "major_topic": false }, { "descriptor": "Hematopoietic Stem Cells", "descriptor_ui": "D006412", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Infant, Newborn", "descriptor_ui": "D007231", "major_topic": false }, { "descriptor": "Stem Cell Niche", "descriptor_ui": "D055153", "major_topic": true } ], "publication": { "conference_name": null, "date": "2022 Aug 2", "date_precision": "day", "issue": "1", "normalized_date": "2022-08-02", "pages": "776", "proceedings_title": null, "publisher": "", "title": "Communications biology", "volume": "5", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Bone marrow imaging reveals the migration dynamics of neonatal hematopoietic stem cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The stiffness of a plant cell in response to an applied force is determined not only by the elasticity of the cell wall but also by turgor pressure and cell geometry, which affect the tension of the cell wall. Although stiffness has been investigated using atomic force microscopy (AFM) and Young's modulus of the cell wall has occasionally been estimated using the contact-stress theory (Hertz theory), the existence of tension has made the study of stiffness more complex. Elastic shell theory has been proposed as an alternative method; however, the estimation of elasticity remains ambiguous. Here, we used finite element method simulations to verify the formula of the elastic shell theory for onion (Allium cepa) cells. We applied the formula and simulations to successfully quantify the turgor pressure and elasticity of a cell in the plane direction using the cell curvature and apparent stiffness measured by AFM. We conclude that tension resulting from turgor pressure regulates cell stiffness, which can be modified by a slight adjustment of turgor pressure in the order of 0.1 MPa. This theoretical analysis reveals a path for understanding forces inherent in plant cells.", "classifications": [ { "id": "JPMJCR2121", "label": "JPMJCR2121", "researcher": "Minako Ueda", "type": "grant" }, { "id": "Tsugawa", "label": "Group Tsugawa", "parent": "Ueda", "type": "group" }, { "id": "Ueda", "label": "Group Ueda", "parent": "Ueda", "type": "group" }, { "id": "Ueda", "label": "Team Ueda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Satoru", "last_name": "Tsugawa", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Yamasaki", "name": null }, { "creator_type": "author", "first_name": "Shota", "last_name": "Horiguchi", "name": null }, { "creator_type": "author", "first_name": "Tianhao", "last_name": "Zhang", "name": null }, { "creator_type": "author", "first_name": "Takara", "last_name": "Muto", "name": null }, { "creator_type": "author", "first_name": "Yosuke", "last_name": "Nakaso", "name": null }, { "creator_type": "author", "first_name": "Kenshiro", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Ryu", "last_name": "Takebayashi", "name": null }, { "creator_type": "author", "first_name": "Kazunori", "last_name": "Okano", "name": null }, { "creator_type": "author", "first_name": "Eri", "last_name": "Akita", "name": null }, { "creator_type": "author", "first_name": "Ryohei", "last_name": "Yasukuni", "name": null }, { "creator_type": "author", "first_name": "Taku", "last_name": "Demura", "name": null }, { "creator_type": "author", "first_name": "Tetsuro", "last_name": "Mimura", "name": null }, { "creator_type": "author", "first_name": "Ken'ichi", "last_name": "Kawaguchi", "name": null }, { "creator_type": "author", "first_name": "Yoichiroh", "last_name": "Hosokawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41598-022-16880-2" }, "pmcid": { "normalized": "PMC9343428" }, "pmid": { "normalized": "35915101" } }, "mesh": [ { "descriptor": "Cell Wall", "descriptor_ui": "D002473", "major_topic": true }, { "descriptor": "Elastic Modulus", "descriptor_ui": "D055119", "major_topic": false }, { "descriptor": "Elasticity", "descriptor_ui": "D004548", "major_topic": false }, { "descriptor": "Microscopy, Atomic Force", "descriptor_ui": "D018625", "major_topic": false }, { "descriptor": "Onions", "descriptor_ui": "D019697", "major_topic": false }, { "descriptor": "Plant Cells", "descriptor_ui": "D059828", "major_topic": true } ], "publication": { "conference_name": null, "date": "2022 Aug 1", "date_precision": "day", "issue": "1", "normalized_date": "2022-08-01", "pages": "13044", "proceedings_title": null, "publisher": "", "title": "Scientific reports", "volume": "12", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Elastic shell theory for plant cell wall stiffness reveals contributions of cell wall elasticity and turgor pressure in AFM measurement.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Pituitary adenomas are characterized by abnormal growth in the pituitary gland. Surgical excision is the first-line treatment for functional (hormone-producing) pituitary adenomas, except for prolactin-producing adenomas; however, complete excision is technically challenging, and many patients require long-term medication after the treatment. In addition, the pathophysiology of pituitary adenomas, such as tumorigenesis, has not been fully understood. Pituitary adenoma pathophysiology has mainly been studied using animal models and animal tumor-derived cell lines. Nevertheless, experimental studies on human pituitary adenomas are difficult because of the significant differences among species and the lack of reliable cell lines. Recently, several methods have been established to differentiate pituitary cells from human pluripotent stem cells (hPSCs). The induced pituitary hormone-producing cells retain the physiological properties already lost in tumor-derived cell lines. Moreover, CRISPR/Cas9 systems have expedited the introduction of causative gene mutations in various malignant tumors into hPSCs. Therefore, hPSC-derived pituitary cells have great potential as a novel platform for studying the pathophysiology of human-specific pituitary adenomas and developing novel drugs. This review presents an overview of the recent progresses in hPSC applications for pituitary research, functional pituitary adenoma pathogenesis, and genome-editing techniques for introducing causative mutations. We also discuss future applications of hPSCs for studying pituitary adenomas.", "classifications": [ { "id": "Yamamoto", "label": "Group Yamamoto", "parent": "Toyoshima", "type": "group" }, { "id": "Toyoshima", "label": "Team Toyoshima", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Ryusaku", "last_name": "Matsumoto", "name": null }, { "creator_type": "author", "first_name": "Hidetaka", "last_name": "Suga", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Arima", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Yamamoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.3390/cancers14153660" }, "pmcid": { "normalized": "PMC9367606" }, "pmid": { "normalized": "35954322" } }, "mesh": [], "publication": { "conference_name": null, "date": "2022 Jul 27", "date_precision": "day", "issue": "15", "normalized_date": "2022-07-27", "pages": "3660", "proceedings_title": null, "publisher": "", "title": "Cancers", "volume": "14", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Disease Modeling of Pituitary Adenoma Using Human Pluripotent Stem Cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Histone lysine methylation is an epigenetic mark that can control gene expression. In particular, H3K9me3 contributes to transcriptional repression by regulating chromatin structure. Successful mitotic progression requires correct timing of chromatin structure changes, including epigenetic marks. However, spatiotemporal information on histone modifications in living cells remains limited. In this study, we created an FRET-based probe for live-cell imaging based on the HP1alpha chromodomain (HP1alphaCD), which binds to H3K9me3. The probe was incorporated into chromatin and the emission ratio decreased after treatment with histone methyltransferase inhibitors, indicating that it successfully traced dynamic changes in H3K9me3. Upon entry into mitosis, the probe's emission ratio transiently increased with a concomitant increase in H3K9me3, then exhibited a stepwise decrease, probably due to loss of HP1alphaCD binding caused by phosphorylation of H3S10 and demethylation of H3K9me3. This probe will be a useful tool for detecting dynamic changes in chromatin structure associated with HP1alpha.", "classifications": [ { "id": "Sodeoka", "label": "Group Sodeoka", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Kazuki", "last_name": "Sasaki", "name": null }, { "creator_type": "author", "first_name": "Michihiro", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Sonoda", "name": null }, { "creator_type": "author", "first_name": "Tilman", "last_name": "Schneider-Poetsch", "name": null }, { "creator_type": "author", "first_name": "Akihiro", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Motoki", "last_name": "Takagi", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Fujishiro", "name": null }, { "creator_type": "author", "first_name": "Yoshihiro", "last_name": "Sohtome", "name": null }, { "creator_type": "author", "first_name": "Kosuke", "last_name": "Dodo", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Umehara", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Aburatani", "name": null }, { "creator_type": "author", "first_name": "Kazuo", "last_name": "Shin-Ya", "name": null }, { "creator_type": "author", "first_name": "Yoichi", "last_name": "Nakao", "name": null }, { "creator_type": "author", "first_name": "Mikiko", "last_name": "Sodeoka", "name": null }, { "creator_type": "author", "first_name": "Minoru", "last_name": "Yoshida", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.chembiol.2022.05.006" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "35728598" } }, "mesh": [ { "descriptor": "Chromatin", "descriptor_ui": "D002843", "major_topic": false }, { "descriptor": "Chromobox Protein Homolog 5", "descriptor_ui": "D000090266", "major_topic": false }, { "descriptor": "Chromosomal Proteins, Non-Histone", "descriptor_ui": "D002868", "major_topic": false }, { "descriptor": "Histones", "descriptor_ui": "D006657", "major_topic": true }, { "descriptor": "Methylation", "descriptor_ui": "D008745", "major_topic": false }, { "descriptor": "Nucleosomes", "descriptor_ui": "D009707", "major_topic": true }, { "descriptor": "Transcription Factors", "descriptor_ui": "D014157", "major_topic": false } ], "publication": { "conference_name": null, "date": "2022 Jul 21", "date_precision": "day", "issue": "7", "normalized_date": "2022-07-21", "pages": "1153-1161.e5", "proceedings_title": null, "publisher": "", "title": "Cell chemical biology", "volume": "29", "year": 2022 }, "ssbd": { "database": [ "ssbd-database-000275" ], "repository": [ "ssbd-repos-000275" ] }, "title": "Visualization of the dynamic interaction between nucleosomal histone H3K9 tri-methylation and HP1alpha chromodomain in living cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "This cross-sectional study aimed to explore specific online behaviours and their association with a range of underlying psychological and other behavioural factors during the COVID-19 pandemic. Eight countries (Italy, Spain, the United Kingdom, Lithuania, Portugal, Japan, Hungary, and Brazil) participated in an international investigation involving 2223 participants (M = 33 years old; SD = 11), 70% of whom were females. Participants were surveyed for specific type of Internet use severity, appearance anxiety, self-compassion, and image and use of performance-enhancing drugs (IPEDs). Results were compared cross-culturally. The mean time spent online was 5 h (SD = +/-3) of daily browsing during the pandemic. The most commonly performed activities included social networking, streaming, and general surfing. A strong association between these online behaviours and appearance anxiety, self-compassion, and IPEDs use was found after adjustment for possible confounders, with higher scores being associated with specific online activities. Significant cross-cultural differences also emerged in terms of the amount of time spent online during the initial stages of the COVID-19 pandemic.", "classifications": [ { "id": "Fujiwara", "label": "Group Fujiwara", "parent": "Fujiwara", "type": "group" }, { "id": "Fujiwara", "label": "Team Fujiwara", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Julius", "last_name": "Burkauskas", "name": null }, { "creator_type": "author", "first_name": "Naomi A.", "last_name": "Fineberg", "name": null }, { "creator_type": "author", "first_name": "Konstantinos", "last_name": "Ioannidis", "name": null }, { "creator_type": "author", "first_name": "Samuel R.", "last_name": "Chamberlain", "name": null }, { "creator_type": "author", "first_name": "Henrietta", "last_name": "Bowden-Jones", "name": null }, { "creator_type": "author", "first_name": "Inga", "last_name": "Griskova-Bulanova", "name": null }, { "creator_type": "author", "first_name": "Aiste", "last_name": "Pranckeviciene", "name": null }, { "creator_type": "author", "first_name": "Artemisa R.", "last_name": "Dores", "name": null }, { "creator_type": "author", "first_name": "Irene P.", "last_name": "Carvalho", "name": null }, { "creator_type": "author", "first_name": "Fernando", "last_name": "Barbosa", "name": null }, { "creator_type": "author", "first_name": "Pierluigi", "last_name": "Simonato", "name": null }, { "creator_type": "author", "first_name": "Ilaria", "last_name": "De Luca", "name": null }, { "creator_type": "author", "first_name": "Rosin", "last_name": "Mooney", "name": null }, { "creator_type": "author", "first_name": "Maria Angeles", "last_name": "Gomez-Martinez", "name": null }, { "creator_type": "author", "first_name": "Zsolt", "last_name": "Demetrovics", "name": null }, { "creator_type": "author", "first_name": "Krisztina Edina", "last_name": "Abel", "name": null }, { "creator_type": "author", "first_name": "Attila", "last_name": "Szabo", "name": null }, { "creator_type": "author", "first_name": "Hironobu", "last_name": "Fujiwara", "name": null }, { "creator_type": "author", "first_name": "Mami", "last_name": "Shibata", "name": null }, { "creator_type": "author", "first_name": "Alejandra R.", "last_name": "Melero-Ventola", "name": null }, { "creator_type": "author", "first_name": "Eva M.", "last_name": "Arroyo-Anllo", "name": null }, { "creator_type": "author", "first_name": "Ricardo M.", "last_name": "Santos-Labrador", "name": null }, { "creator_type": "author", "first_name": "Kei", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Francesco", "last_name": "Di Carlo", "name": null }, { "creator_type": "author", "first_name": "Cristina", "last_name": "Monteiro", "name": null }, { "creator_type": "author", "first_name": "Giovanni", "last_name": "Martinotti", "name": null }, { "creator_type": "author", "first_name": "Ornella", "last_name": "Corazza", "name": null } ], "identifiers": { "doi": { "normalized": "10.3390/ijerph19148823" }, "pmcid": { "normalized": "PMC9323465" }, "pmid": { "normalized": "35886679" } }, "mesh": [ { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Anxiety", "descriptor_ui": "D001007", "major_topic": false }, { "descriptor": "Anxiety Disorders", "descriptor_ui": "D001008", "major_topic": false }, { "descriptor": "COVID-19", "descriptor_ui": "D000086382", "major_topic": true }, { "descriptor": "Cross-Sectional Studies", "descriptor_ui": "D003430", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Pandemics", "descriptor_ui": "D058873", "major_topic": false } ], "publication": { "conference_name": null, "date": "2022 Jul 20", "date_precision": "day", "issue": "14", "normalized_date": "2022-07-20", "pages": "8823", "proceedings_title": null, "publisher": "", "title": "International journal of environmental research and public health", "volume": "19", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Online Behaviours during the COVID-19 Pandemic and Their Associations with Psychological Factors: An International Exploratory Study.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The increase in the expectations of artificial intelligence (AI) technology has led to machine learning technology being actively used in the medical field. Non-negative matrix factorization (NMF) is a machine learning technique used for image analysis, speech recognition, and language processing; recently, it is being applied to medical research. Precision medicine, wherein important information is extracted from large-scale medical data to provide optimal medical care for every individual, is considered important in medical policies globally, and the application of machine learning techniques to this end is being handled in several ways. NMF is also introduced differently because of the characteristics of its algorithms. In this review, the importance of NMF in the field of medicine, with a focus on the field of oncology, is described by explaining the mathematical science of NMF and the characteristics of the algorithm, providing examples of how NMF can be used to establish precision medicine, and presenting the challenges of NMF. Finally, the direction regarding the effective use of NMF in the field of oncology is also discussed.", "classifications": [ { "id": "Hamamoto", "label": "Group Hamamoto", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Group Okamoto", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Ryuji", "last_name": "Hamamoto", "name": null }, { "creator_type": "author", "first_name": "Ken", "last_name": "Takasawa", "name": null }, { "creator_type": "author", "first_name": "Hidenori", "last_name": "Machino", "name": null }, { "creator_type": "author", "first_name": "Kazuma", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Amina", "last_name": "Bolatkan", "name": null }, { "creator_type": "author", "first_name": "Norio", "last_name": "Shinkai", "name": null }, { "creator_type": "author", "first_name": "Akira", "last_name": "Sakai", "name": null }, { "creator_type": "author", "first_name": "Rina", "last_name": "Aoyama", "name": null }, { "creator_type": "author", "first_name": "Masayoshi", "last_name": "Yamada", "name": null }, { "creator_type": "author", "first_name": "Ken", "last_name": "Asada", "name": null }, { "creator_type": "author", "first_name": "Masaaki", "last_name": "Komatsu", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Okamoto", "name": null }, { "creator_type": "author", "first_name": "Hirokazu", "last_name": "Kameoka", "name": null }, { "creator_type": "author", "first_name": "Syuzo", "last_name": "Kaneko", "name": null } ], "identifiers": { "doi": { "normalized": "10.1093/bib/bbac246" }, "pmcid": { "normalized": "PMC9294421" }, "pmid": { "normalized": "35788277" } }, "mesh": [ { "descriptor": "Algorithms", "descriptor_ui": "D000465", "major_topic": false }, { "descriptor": "Artificial Intelligence", "descriptor_ui": "D001185", "major_topic": true }, { "descriptor": "Machine Learning", "descriptor_ui": "D000069550", "major_topic": false }, { "descriptor": "Precision Medicine", "descriptor_ui": "D057285", "major_topic": true } ], "publication": { "conference_name": null, "date": "2022 Jul 18", "date_precision": "day", "issue": "4", "normalized_date": "2022-07-18", "pages": "bbac246", "proceedings_title": null, "publisher": "", "title": "Briefings in bioinformatics", "volume": "23", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Application of non-negative matrix factorization in oncology: one approach for establishing precision medicine.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The physical causes of organ malformation remain largely unclear in most cases due to a lack of information on tissue/cell dynamics. Here, we address this issue by considering onset of cyclopia in sonic hedgehog (SHH)-inhibited chick embryos. We show that ventral forebrain-specific self-organization ability driven by SHH-dependent polarized patterns in cell shape, phosphorylated myosin localization, and collective cell motion promotes optic vesicle elongation during normal development. Stress loading tests revealed that these polarized dynamics result from mechanical responses. In particular, stress and active tissue deformation satisfy orthogonality, defining an SHH-regulated morphogenetic law. Without SHH signaling, cells cannot detect the direction of stress and move randomly, leading to insufficient optic vesicle elongation and consequently a cyclopia phenotype. Since polarized tissue/cell dynamics are common in organogenesis, cell disorientation caused by loss of mechanosensation could be a pathogenic mechanism for other malformations.", "classifications": [ { "id": "JPMJCR2025", "label": "JPMJCR2025", "researcher": "Yoshihiro Morishita", "type": "grant" }, { "id": "Morishita", "label": "Group Morishita", "parent": "Morishita", "type": "group" }, { "id": "Morishita", "label": "Team Morishita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Daisuke", "last_name": "Ohtsuka", "name": null }, { "creator_type": "author", "first_name": "Naoki", "last_name": "Kida", "name": null }, { "creator_type": "author", "first_name": "Sang-Woo", "last_name": "Lee", "name": null }, { "creator_type": "author", "first_name": "Naofumi", "last_name": "Kawahira", "name": null }, { "creator_type": "author", "first_name": "Yoshihiro", "last_name": "Morishita", "name": null } ], "identifiers": { "doi": { "normalized": "10.1126/sciadv.abn2330" }, "pmcid": { "normalized": "PMC9278851" }, "pmid": { "normalized": "35857502" } }, "mesh": [], "publication": { "conference_name": null, "date": "2022 Jul 15", "date_precision": "day", "issue": "28", "normalized_date": "2022-07-15", "pages": "eabn2330", "proceedings_title": null, "publisher": "", "title": "Science advances", "volume": "8", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Cell disorientation by loss of SHH-dependent mechanosensation causes cyclopia.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Abnormal mitochondrial fragmentation by dynamin-related protein1 (Drp1) is associated with the progression of aging-associated heart diseases, including heart failure and myocardial infarction (MI). Here, we report a protective role of outer mitochondrial membrane (OMM)-localized E3 ubiquitin ligase MITOL/MARCH5 against cardiac senescence and MI, partly through Drp1 clearance by OMM-associated degradation (OMMAD). Persistent Drp1 accumulation in cardiomyocyte-specific MITOL conditional-knockout mice induced mitochondrial fragmentation and dysfunction, including reduced ATP production and increased ROS generation, ultimately leading to myocardial senescence and chronic heart failure. Furthermore, ischemic stress-induced acute downregulation of MITOL, which permitted mitochondrial accumulation of Drp1, resulted in mitochondrial fragmentation. Adeno-associated virus-mediated delivery of the MITOL gene to cardiomyocytes ameliorated cardiac dysfunction induced by MI. Our findings suggest that OMMAD activation by MITOL can be a therapeutic target for aging-associated heart diseases, including heart failure and MI.", "classifications": [ { "id": "Nishida", "label": "Group Nishida", "parent": "Nishida", "type": "group" }, { "id": "Nishimura", "label": "Group Nishimura", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Takeshi", "last_name": "Tokuyama", "name": null }, { "creator_type": "author", "first_name": "Hideki", "last_name": "Uosaki", "name": null }, { "creator_type": "author", "first_name": "Ayumu", "last_name": "Sugiura", "name": null }, { "creator_type": "author", "first_name": "Gen", "last_name": "Nishitai", "name": null }, { "creator_type": "author", "first_name": "Keisuke", "last_name": "Takeda", "name": null }, { "creator_type": "author", "first_name": "Shun", "last_name": "Nagashima", "name": null }, { "creator_type": "author", "first_name": "Isshin", "last_name": "Shiiba", "name": null }, { "creator_type": "author", "first_name": "Naoki", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Taku", "last_name": "Amo", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Mohri", "name": null }, { "creator_type": "author", "first_name": "Akiyuki", "last_name": "Nishimura", "name": null }, { "creator_type": "author", "first_name": "Motohiro", "last_name": "Nishida", "name": null }, { "creator_type": "author", "first_name": "Ayumu", "last_name": "Konno", "name": null }, { "creator_type": "author", "first_name": "Hirokazu", "last_name": "Hirai", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Ishido", "name": null }, { "creator_type": "author", "first_name": "Takahiro", "last_name": "Yoshizawa", "name": null }, { "creator_type": "author", "first_name": "Takayuki", "last_name": "Shindo", "name": null }, { "creator_type": "author", "first_name": "Shingo", "last_name": "Takada", "name": null }, { "creator_type": "author", "first_name": "Shintaro", "last_name": "Kinugawa", "name": null }, { "creator_type": "author", "first_name": "Ryoko", "last_name": "Inatome", "name": null }, { "creator_type": "author", "first_name": "Shigeru", "last_name": "Yanagi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.isci.2022.104582" }, "pmcid": { "normalized": "PMC9249672" }, "pmid": { "normalized": "35789860" } }, "mesh": [], "publication": { "conference_name": null, "date": "2022 Jul 15", "date_precision": "day", "issue": "7", "normalized_date": "2022-07-15", "pages": "104582", "proceedings_title": null, "publisher": "", "title": "iScience", "volume": "25", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Protective roles of MITOL against myocardial senescence and ischemic injury partly via Drp1 regulation.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Point-mutations of MEK1, a central component of ERK signaling, are present in cancer and RASopathies, but their precise biological effects remain obscure. Here, we report a mutant MEK1 structure that uncovers the mechanisms underlying abnormal activities of cancer- and RASopathy-associated MEK1 mutants. These two classes of MEK1 mutations differentially impact on spatiotemporal dynamics of ERK signaling, cellular transcriptional programs, gene expression profiles, and consequent biological outcomes. By making use of such distinct characteristics of the MEK1 mutants, we identified cancer- and RASopathy-signature genes that may serve as diagnostic markers or therapeutic targets for these diseases. In particular, two AKT-inhibitor molecules, PHLDA1 and 2, are simultaneously upregulated by oncogenic ERK signaling, and mediate cancer-specific ERK-AKT crosstalk. The combined expression of PHLDA1/2 is critical to confer resistance to ERK pathway-targeted therapeutics on cancer cells. Finally, we propose a therapeutic strategy to overcome this drug resistance. Our data provide vital insights into the etiology, diagnosis, and therapeutic strategy of cancers and RASopathies.", "classifications": [ { "id": "JPMJCR2022", "label": "JPMJCR2022", "researcher": "Mutsuhiro Takekawa", "type": "grant" }, { "id": "Takekawa", "label": "Group Takekawa", "parent": "Takekawa", "type": "group" }, { "id": "Takekawa", "label": "Team Takekawa", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yuji", "last_name": "Kubota", "name": null }, { "creator_type": "author", "first_name": "Yuko", "last_name": "Fujioka", "name": null }, { "creator_type": "author", "first_name": "Ashwini", "last_name": "Patil", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Takagi", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Matsubara", "name": null }, { "creator_type": "author", "first_name": "Masatomi", "last_name": "Iijima", "name": null }, { "creator_type": "author", "first_name": "Isao", "last_name": "Momose", "name": null }, { "creator_type": "author", "first_name": "Ryosuke", "last_name": "Naka", "name": null }, { "creator_type": "author", "first_name": "Kenta", "last_name": "Nakai", "name": null }, { "creator_type": "author", "first_name": "Nobuo N.", "last_name": "Noda", "name": null }, { "creator_type": "author", "first_name": "Mutsuhiro", "last_name": "Takekawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41467-022-31690-w" }, "pmcid": { "normalized": "PMC9279491" }, "pmid": { "normalized": "35831322" } }, "mesh": [ { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "MAP Kinase Kinase 1", "descriptor_ui": "D048369", "major_topic": false }, { "descriptor": "MAP Kinase Signaling System", "descriptor_ui": "D020935", "major_topic": false }, { "descriptor": "Mitogen-Activated Protein Kinase Kinases", "descriptor_ui": "D020929", "major_topic": false }, { "descriptor": "Neoplasms", "descriptor_ui": "D009369", "major_topic": true }, { "descriptor": "Protein Kinase Inhibitors", "descriptor_ui": "D047428", "major_topic": false }, { "descriptor": "Proto-Oncogene Proteins c-akt", "descriptor_ui": "D051057", "major_topic": true }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false } ], "publication": { "conference_name": null, "date": "2022 Jul 13", "date_precision": "day", "issue": "1", "normalized_date": "2022-07-13", "pages": "4063", "proceedings_title": null, "publisher": "", "title": "Nature communications", "volume": "13", "year": 2022 }, "ssbd": { "database": [ "ssbd-database-000257" ], "repository": [ "ssbd-repos-000257" ] }, "title": "Qualitative differences in disease-associated MEK mutants reveal molecular signatures and aberrant signaling-crosstalk in cancer.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Copper-zinc superoxide dismutase (SOD1) has been proposed as one of the causative proteins of amyotrophic lateral sclerosis (ALS). The accumulation of non-native conformers, oligomers, and aggregates of SOD1 in motor neurons is considered responsible for this disease. However, it remains unclear which specific feature of these species induces the onset of ALS. In this study, we showed that disulfide-linked oligomers of denatured SOD1 exhibit pro-oxidant activity. Substituting all the cysteine residues in the free thiol state with serine resulted in the loss of both the propensity to oligomerize and the increase in pro-oxidant activity after denaturation. In contrast, these cysteine mutants oligomerized and acquired the pro-oxidant activity after denaturation in the presence of a reductant that cleaves the intramolecular disulfide bond. These results indicate that one of the toxicities of SOD1 oligomers is the pro-oxidant activity induced by scrambling of the disulfide bonds. Small oligomers such as dimers and trimers exhibit stronger pro-oxidant activity than large oligomers and aggregates, consistent with the trend of the cytotoxicity of oligomers and aggregates reported in previous studies. We propose that the cleavage of the intramolecular disulfide bond accompanied by the oligomerization reduces the substrate specificity of SOD1, leading to the non-native enzymatic activity.", "classifications": [ { "id": "JPMJCR2024", "label": "JPMJCR2024", "researcher": "Motohiro Nishida", "type": "grant" }, { "id": "Nakabayashi", "label": "Group Nakabayashi", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Group Nishida", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Kosuke", "last_name": "Yamazaki", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Tahara", "name": null }, { "creator_type": "author", "first_name": "Takumi", "last_name": "Ohyama", "name": null }, { "creator_type": "author", "first_name": "Kunisato", "last_name": "Kuroi", "name": null }, { "creator_type": "author", "first_name": "Takakazu", "last_name": "Nakabayashi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41598-022-15701-w" }, "pmcid": { "normalized": "PMC9273606" }, "pmid": { "normalized": "35817830" } }, "mesh": [ { "descriptor": "Amyotrophic Lateral Sclerosis", "descriptor_ui": "D000690", "major_topic": true }, { "descriptor": "Cysteine", "descriptor_ui": "D003545", "major_topic": false }, { "descriptor": "Disulfides", "descriptor_ui": "D004220", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": false }, { "descriptor": "Reactive Oxygen Species", "descriptor_ui": "D017382", "major_topic": false }, { "descriptor": "Superoxide Dismutase", "descriptor_ui": "D013482", "major_topic": false }, { "descriptor": "Superoxide Dismutase-1", "descriptor_ui": "D000072105", "major_topic": false } ], "publication": { "conference_name": null, "date": "2022 Jul 11", "date_precision": "day", "issue": "1", "normalized_date": "2022-07-11", "pages": "11750", "proceedings_title": null, "publisher": "", "title": "Scientific reports", "volume": "12", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "SOD1 gains pro-oxidant activity upon aberrant oligomerization: change in enzymatic activity by intramolecular disulfide bond cleavage.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Abstract Germ cells are unique in engendering totipotency, yet the mechanisms underlying this capacity remain elusive. Here, we perform comprehensive and in-depth nucleome analysis of mouse germ-cell development in?vitro, encompassing pluripotent precursors, primordial germ cells (PGCs) before and after epigenetic reprogramming, and spermatogonia/spermatogonial stem cells (SSCs). Although epigenetic reprogramming, including genome-wide DNA de-methylation, creates broadly open chromatin with abundant enhancer-like signatures, the augmented chromatin insulation safeguards transcriptional fidelity. These insulatory constraints are then erased en masse for spermatogonial development. Notably, despite distinguishing epigenetic programming, including global DNA re-methylation, the PGCs-to-spermatogonia/SSCs development entails further euchromatization. This accompanies substantial erasure of lamina-associated domains, generating spermatogonia/SSCs with a minimal peripheral attachment of chromatin except for pericentromeres?an architecture conserved in primates. Accordingly, faulty nucleome maturation, including persistent insulation and improper euchromatization, leads to impaired spermatogenic potential. Given that PGCs after epigenetic reprogramming serve as oogenic progenitors as well, our findings elucidate a principle for the nucleome programming that creates gametogenic progenitors in both sexes, defining a basis for nuclear totipotency.", "classifications": [ { "id": "Yamamoto", "label": "Group Yamamoto", "parent": "Toyoshima", "type": "group" }, { "id": "Toyoshima", "label": "Team Toyoshima", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Masahiro", "last_name": "Nagano", "name": null }, { "creator_type": "author", "first_name": "Bo", "last_name": "Hu", "name": null }, { "creator_type": "author", "first_name": "Shihori", "last_name": "Yokobayashi", "name": null }, { "creator_type": "author", "first_name": "Akitoshi", "last_name": "Yamamura", "name": null }, { "creator_type": "author", "first_name": "Fumiya", "last_name": "Umemura", "name": null }, { "creator_type": "author", "first_name": "Mariel", "last_name": "Coradin", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Ohta", "name": null }, { "creator_type": "author", "first_name": "Yukihiro", "last_name": "Yabuta", "name": null }, { "creator_type": "author", "first_name": "Yukiko", "last_name": "Ishikura", "name": null }, { "creator_type": "author", "first_name": "Ikuhiro", "last_name": "Okamoto", "name": null }, { "creator_type": "author", "first_name": "Hiroki", "last_name": "Ikeda", "name": null }, { "creator_type": "author", "first_name": "Naofumi", "last_name": "Kawahira", "name": null }, { "creator_type": "author", "first_name": "Yoshiaki", "last_name": "Nosaka", "name": null }, { "creator_type": "author", "first_name": "Sakura", "last_name": "Shimizu", "name": null }, { "creator_type": "author", "first_name": "Yoji", "last_name": "Kojima", "name": null }, { "creator_type": "author", "first_name": "Ken", "last_name": "Mizuta", "name": null }, { "creator_type": "author", "first_name": "Tomoko", "last_name": "Kasahara", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Imoto", "name": null }, { "creator_type": "author", "first_name": "Killian", "last_name": "Meehan", "name": null }, { "creator_type": "author", "first_name": "Roman", "last_name": "Stocsits", "name": null }, { "creator_type": "author", "first_name": "Gordana", "last_name": "Wutz", "name": null }, { "creator_type": "author", "first_name": "Yasuaki", "last_name": "Hiraoka", "name": null }, { "creator_type": "author", "first_name": "Yasuhiro", "last_name": "Murakawa", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Kikue", "last_name": "Tachibana", "name": null }, { "creator_type": "author", "first_name": "Jan-Michel", "last_name": "Peters", "name": null }, { "creator_type": "author", "first_name": "Leonid A", "last_name": "Mirny", "name": null }, { "creator_type": "author", "first_name": "Benjamin A", "last_name": "Garcia", "name": null }, { "creator_type": "author", "first_name": "Jacek", "last_name": "Majewski", "name": null }, { "creator_type": "author", "first_name": "Mitinori", "last_name": "Saitou", "name": null } ], "identifiers": { "doi": { "normalized": "10.15252/embj.2022110600" }, "pmcid": { "normalized": null }, "pmid": { "normalized": null } }, "mesh": [], "publication": { "conference_name": null, "date": "2022-07-04", "date_precision": "day", "issue": "13", "normalized_date": "2022-07-04", "pages": "e110600", "proceedings_title": null, "publisher": "John Wiley & Sons, Ltd", "title": "The EMBO Journal", "volume": "41", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Nucleome programming is required for the foundation of totipotency in mammalian germline development", "url": "https://www.embopress.org/doi/full/10.15252/embj.2022110600", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Simultaneous observation of drug distribution at the effector site and subsequent cell response are essential in the drug development process. However, few studies have visualized the drug itself and biomolecular interactions in living cells. Here, we used label-free Raman microscopy to investigate drug-induced cytotoxicity and visualize drug uptake and subcellular localization by its specific molecular fingerprint. A redox-sensitive Raman microscope detected the decrease of reduced cytochrome c (cyt c) after Actinomycin D (ActD) treatment in a time-dependent and dose-dependent format. Immunofluorescence staining of cyt c suggested that the release of cyt c was not the major cause. Combining Raman microscopy with conventional biological methods, we reported that the oxidization of cyt c is an early cytotoxicity marker prior to the release of cyt c. Moreover, as the spectral properties of ActD are sensitive to the surrounding environment, subcellular localization of ActD was visualized sensitively by the weak autofluorescence, and the intercalation of ActD into DNA was detected by shifted Raman peaks, allowing for parallel observation of drug uptake and the mechanism of action. In this research, we achieved simultaneous observation of cytotoxicity and cellular drug uptake by Raman microscopy, which could facilitate a precise understanding of pharmacological effects and predict potential drug toxicity in the future.", "classifications": [ { "id": "JPMJCR1925", "label": "JPMJCR1925", "researcher": "Katsumasa Fujita", "type": "grant" }, { "id": "Fujita", "label": "Group Fujita", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Menglu", "last_name": "Li", "name": null }, { "creator_type": "author", "first_name": "Hao-Xiang", "last_name": "Liao", "name": null }, { "creator_type": "author", "first_name": "Kazuki", "last_name": "Bando", "name": null }, { "creator_type": "author", "first_name": "Yasunori", "last_name": "Nawa", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Fujita", "name": null }, { "creator_type": "author", "first_name": "Katsumasa", "last_name": "Fujita", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/acs.analchem.2c00293" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "35786862" } }, "mesh": [ { "descriptor": "Cytochromes c", "descriptor_ui": "D045304", "major_topic": true }, { "descriptor": "Dactinomycin", "descriptor_ui": "D003609", "major_topic": false }, { "descriptor": "Microscopy", "descriptor_ui": "D008853", "major_topic": false }, { "descriptor": "Optical Imaging", "descriptor_ui": "D061848", "major_topic": false }, { "descriptor": "Spectrum Analysis, Raman", "descriptor_ui": "D013059", "major_topic": true } ], "publication": { "conference_name": null, "date": "2022-07", "date_precision": "month", "issue": "28", "normalized_date": "2022-07", "pages": "10019-10026", "proceedings_title": null, "publisher": "", "title": "Analytical Chemistry", "volume": "94", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Label-Free Monitoring of Drug-Induced Cytotoxicity and Its Molecular Fingerprint by Live-Cell Raman and Autofluorescence Imaging", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Ribosome biogenesis is an energetically expensive program that is dictated by nutrient availability. Here we report that nutrient deprivation severely impairs precursor ribosomal RNA (pre-rRNA) processing and leads to the accumulation of unprocessed rRNAs. Upon nutrient restoration, pre-rRNAs stored under starvation are processed into mature rRNAs that are utilized for ribosome biogenesis. Failure to accumulate pre-rRNAs under nutrient stress leads to perturbed ribosome assembly upon nutrient restoration and subsequent apoptosis via uL5/uL18-mediated activation of p53. Restoration of glutamine alone activates p53 by triggering uL5/uL18 translation. Induction of uL5/uL18 protein synthesis by glutamine is dependent on the translation factor eukaryotic elongation factor 2 (eEF2), which is in turn dependent on Raf/MEK/ERK signaling. Depriving cells of glutamine prevents the activation of p53 by rRNA synthesis inhibitors. Our data reveals a mechanism that tumor cells can exploit to suppress p53-mediated apoptosis during fluctuations in environmental nutrient availability.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Melvin", "last_name": "Pan", "name": null }, { "creator_type": "author", "first_name": "Christiane", "last_name": "Zorbas", "name": null }, { "creator_type": "author", "first_name": "Maki", "last_name": "Sugaya", "name": null }, { "creator_type": "author", "first_name": "Kensuke", "last_name": "Ishiguro", "name": null }, { "creator_type": "author", "first_name": "Miki", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Miyuki", "last_name": "Nishida", "name": null }, { "creator_type": "author", "first_name": "Hai-Feng", "last_name": "Zhang", "name": null }, { "creator_type": "author", "first_name": "Marco M.", "last_name": "Candeias", "name": null }, { "creator_type": "author", "first_name": "Akimitsu", "last_name": "Okamoto", "name": null }, { "creator_type": "author", "first_name": "Takamasa", "last_name": "Ishikawa", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Aburatani", "name": null }, { "creator_type": "author", "first_name": "Juro", "last_name": "Sakai", "name": null }, { "creator_type": "author", "first_name": "Yoshihiro", "last_name": "Matsumura", "name": null }, { "creator_type": "author", "first_name": "Tsutomu", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Christopher G.", "last_name": "Proud", "name": null }, { "creator_type": "author", "first_name": "Denis L. J.", "last_name": "Lafontaine", "name": null }, { "creator_type": "author", "first_name": "Tsuyoshi", "last_name": "Osawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41467-022-31418-w" }, "pmcid": { "normalized": "PMC9240073" }, "pmid": { "normalized": "35764642" } }, "mesh": [ { "descriptor": "Glutamine", "descriptor_ui": "D005973", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Neoplasms", "descriptor_ui": "D009369", "major_topic": true }, { "descriptor": "Nucleic Acid Synthesis Inhibitors", "descriptor_ui": "D019384", "major_topic": false }, { "descriptor": "Ribosomes", "descriptor_ui": "D012270", "major_topic": false }, { "descriptor": "RNA Precursors", "descriptor_ui": "D012322", "major_topic": false }, { "descriptor": "RNA, Ribosomal", "descriptor_ui": "D012335", "major_topic": false }, { "descriptor": "Tumor Suppressor Protein p53", "descriptor_ui": "D016159", "major_topic": false } ], "publication": { "conference_name": null, "date": "2022 Jun 28", "date_precision": "day", "issue": "1", "normalized_date": "2022-06-28", "pages": "3706", "proceedings_title": null, "publisher": "", "title": "Nature communications", "volume": "13", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Glutamine deficiency in solid tumor cells confers resistance to ribosomal RNA synthesis inhibitors.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Retarded revascularization after progressive occlusion of large conductance arteries is a major cause of bad prognosis for peripheral artery disease (PAD). However, pharmacological treatment for PAD is still limited. We previously reported that suppression of transient receptor potential canonical (TRPC) 6 channel activity in vascular smooth muscle cells (VSMCs) facilitates VSMC differentiation without affecting proliferation and migration. In this study, we found that 1-benzilpiperadine derivative (1-BP), a selective inhibitor for TRPC3 and TRPC6 channel activities, induced VSMC differentiation. 1-BP-treated mice showed increased capillary arterialization and improvement of peripheral circulation and skeletal muscle mass after hind-limb ischemia (HLI) in mice. 1-BP had no additive effect on the facilitation of blood flow recovery after HLI in TRPC6-deficient mice, suggesting that suppression of TRPC6 underlies facilitation of the blood flow recovery by 1-BP. 1-BP also improved vascular nitric oxide bioavailability and blood flow recovery after HLI in hypercholesterolemic mice with endothelial dysfunction, suggesting the retrograde interaction from VSMCs to endothelium. These results suggest that 1-BP becomes a potential seed for PAD treatments that target vascular TRPC6 channels.", "classifications": [ { "id": "JPMJCR2024", "label": "JPMJCR2024", "researcher": "Motohiro Nishida", "type": "grant" }, { "id": "Nishida", "label": "Group Nishida", "parent": "Nishida", "type": "group" }, { "id": "Nishimura", "label": "Group Nishimura", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Tsukasa", "last_name": "Shimauchi", "name": null }, { "creator_type": "author", "first_name": "Takuro", "last_name": "Numaga-Tomita", "name": null }, { "creator_type": "author", "first_name": "Yuri", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Morimoto", "name": null }, { "creator_type": "author", "first_name": "Kosuke", "last_name": "Sakata", "name": null }, { "creator_type": "author", "first_name": "Ryosuke", "last_name": "Matsukane", "name": null }, { "creator_type": "author", "first_name": "Akiyuki", "last_name": "Nishimura", "name": null }, { "creator_type": "author", "first_name": "Kazuhiro", "last_name": "Nishiyama", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Shibuta", "name": null }, { "creator_type": "author", "first_name": "Yutoku", "last_name": "Horiuchi", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Kurose", "name": null }, { "creator_type": "author", "first_name": "Sang Geon", "last_name": "Kim", "name": null }, { "creator_type": "author", "first_name": "Yasuteru", "last_name": "Urano", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Ohshima", "name": null }, { "creator_type": "author", "first_name": "Motohiro", "last_name": "Nishida", "name": null } ], "identifiers": { "doi": { "normalized": "10.3390/cells11132041" }, "pmcid": { "normalized": "PMC9266111" }, "pmid": { "normalized": "35805125" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Arteries", "descriptor_ui": "D001158", "major_topic": false }, { "descriptor": "Ischemia", "descriptor_ui": "D007511", "major_topic": true }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Muscle, Skeletal", "descriptor_ui": "D018482", "major_topic": false }, { "descriptor": "Myocytes, Smooth Muscle", "descriptor_ui": "D032389", "major_topic": true }, { "descriptor": "TRPC Cation Channels", "descriptor_ui": "D050052", "major_topic": false }, { "descriptor": "TRPC6 Cation Channel", "descriptor_ui": "D000074287", "major_topic": false } ], "publication": { "conference_name": null, "date": "2022-06-27", "date_precision": "day", "issue": "13", "normalized_date": "2022-06-27", "pages": "2041", "proceedings_title": null, "publisher": "", "title": "Cells", "volume": "11", "year": 2022 }, "ssbd": { "database": [ "ssbd-database-000253" ], "repository": [ "ssbd-repos-000253" ] }, "title": "A TRPC3/6 Channel Inhibitor Promotes Arteriogenesis after Hind-Limb Ischemia", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Liquid–liquid phase separation (LLPS) is an important phenomenon in biology, and it is desirable to develop quantitative methods to analyze protein droplets generated by LLPS. This study quantified the change in protein concentration in a droplet in label-free and single-droplet conditions using Raman imaging and the Raman band of water as an intensity standard. Small changes in the protein concentration with variations in pH and salt concentration were observed, and it was shown that the concentration in the droplet decreases as the conditions become less favorable for droplet formation. The effect of exposure to 1,6-hexanediol was also examined, and this additive was found to decrease the protein concentration in the droplet. A model can be proposed in which the addition of 1,6-hexanediol reduces the protein concentration in the droplet, and the droplet disappears when the concentration falls below a certain threshold value.", "classifications": [ { "id": "Nakabayashi", "label": "Group Nakabayashi", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Kohei", "last_name": "Yokosawa", "name": null }, { "creator_type": "author", "first_name": "Shinji", "last_name": "Kajimoto", "name": null }, { "creator_type": "author", "first_name": "Daiki", "last_name": "Shibata", "name": null }, { "creator_type": "author", "first_name": "Kunisato", "last_name": "Kuroi", "name": null }, { "creator_type": "author", "first_name": "Tomohiro", "last_name": "Konno", "name": null }, { "creator_type": "author", "first_name": "Takakazu", "last_name": "Nakabayashi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/acs.jpclett.2c00962" }, "pmcid": { "normalized": null }, "pmid": { "normalized": null } }, "mesh": [], "publication": { "conference_name": null, "date": "2022-06-23", "date_precision": "day", "issue": "24", "normalized_date": "2022-06-23", "pages": "5692-5697", "proceedings_title": null, "publisher": "American Chemical Society", "title": "The Journal of Physical Chemistry Letters", "volume": "13", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Concentration Quantification of the Low-Complexity Domain of Fused in Sarcoma inside a Single Droplet and Effects of Solution Parameters", "url": "https://doi.org/10.1021/acs.jpclett.2c00962", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Human primed embryonic stem cells (ESCs) are known to be converted to cells with several trophoblast properties, but it has remained controversial whether this phenomenon represents the inherent differentiation competence of human primed ESCs to trophoblast lineages. In this study, we report that chemical blockage of ACTIVIN/NODAL and FGF signals is sufficient to steer human primed ESCs into GATA3-expressing cells that give rise to placental hormone-producing syncytia analogous to syncytiotrophoblasts of the post-implantation stage of the human embryo. Despite their cytological similarity to syncytiotrophoblasts, these syncytia arise from the non-trophoblastic differentiation trajectory that recapitulates amniogenesis. These results provide insights into the possible extraembryonic differentiation pathway that is unique in primate embryogenesis.", "classifications": [ { "id": "Eiraku", "label": "Group Eiraku", "parent": "Eiraku", "type": "group" }, { "id": "Eiraku", "label": "Team Eiraku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Masatoshi", "last_name": "Ohgushi", "name": null }, { "creator_type": "author", "first_name": "Nobuko", "last_name": "Taniyama", "name": null }, { "creator_type": "author", "first_name": "Alexis", "last_name": "Vandenbon", "name": null }, { "creator_type": "author", "first_name": "Mototsugu", "last_name": "Eiraku", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.celrep.2022.110973" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "35732132" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Embryonic Stem Cells", "descriptor_ui": "D053595", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Giant Cells", "descriptor_ui": "D015726", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Placenta", "descriptor_ui": "D010920", "major_topic": true }, { "descriptor": "Pregnancy", "descriptor_ui": "D011247", "major_topic": false }, { "descriptor": "Trophoblasts", "descriptor_ui": "D014327", "major_topic": true } ], "publication": { "conference_name": null, "date": "2022 Jun 21", "date_precision": "day", "issue": "12", "normalized_date": "2022-06-21", "pages": "110973", "proceedings_title": null, "publisher": "", "title": "Cell reports", "volume": "39", "year": 2022 }, "ssbd": { "database": [ "ssbd-database-000282" ], "repository": [ "ssbd-repos-000282" ] }, "title": "Delamination of trophoblast-like syncytia from the amniotic ectodermal analogue in human primed embryonic stem cell-based differentiation model.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Angioimmunoblastic T-cell lymphoma (AITL) is an intractable type of T-cell lymphoma. We and others have identified that the p.Gly17Val RHOA mutation is specifically identified in AITL. We herein report a patient whose condition deteriorated, resulting from massive pericardial effusion one month after undergoing autologous transplantation for AITL. He was diagnosed with cardiac tamponade caused by AITL recurrence in the presence of the p.Gly17Val RHOA mutation as well as T-lineage cells with an aberrant immune-phenotype in the pericardial effusion. This case suggests that a precision medicine approach by detecting the presence of a p.Gly17Val RHOA mutation is useful for the management of AITL.", "classifications": [ { "id": "Nishikii", "label": "Group Nishikii", "parent": "Shintaku", "type": "group" }, { "id": "Shintaku", "label": "Team Shintaku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yuri", "last_name": "Tsuboi", "name": null }, { "creator_type": "author", "first_name": "Yumoe", "last_name": "Iimura", "name": null }, { "creator_type": "author", "first_name": "Fumiaki", "last_name": "Matsumura", "name": null }, { "creator_type": "author", "first_name": "Toru", "last_name": "Nanmoku", "name": null }, { "creator_type": "author", "first_name": "Sakurako", "last_name": "Suma", "name": null }, { "creator_type": "author", "first_name": "Ryota", "last_name": "Matsuoka", "name": null }, { "creator_type": "author", "first_name": "Tomoki", "last_name": "Nakagawa", "name": null }, { "creator_type": "author", "first_name": "Daishi", "last_name": "Nakagawa", "name": null }, { "creator_type": "author", "first_name": "Yasuhito", "last_name": "Suehara", "name": null }, { "creator_type": "author", "first_name": "Keiichiro", "last_name": "Hattori", "name": null }, { "creator_type": "author", "first_name": "Kimi", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Yumiko", "last_name": "Maruyama", "name": null }, { "creator_type": "author", "first_name": "Tatsuhiro", "last_name": "Sakamoto", "name": null }, { "creator_type": "author", "first_name": "Yasuhisa", "last_name": "Yokoyama", "name": null }, { "creator_type": "author", "first_name": "Takayasu", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Naoki", "last_name": "Kurita", "name": null }, { "creator_type": "author", "first_name": "Hidekazu", "last_name": "Nishikii", "name": null }, { "creator_type": "author", "first_name": "Naoshi", "last_name": "Obara", "name": null }, { "creator_type": "author", "first_name": "Masaki", "last_name": "Ieda", "name": null }, { "creator_type": "author", "first_name": "Shigeru", "last_name": "Chiba", "name": null }, { "creator_type": "author", "first_name": "Mamiko", "last_name": "Sakata-Yanagimoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.2169/internalmedicine.9248-22" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "35732446" } }, "mesh": [ { "descriptor": "Cardiac Tamponade", "descriptor_ui": "D002305", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Immunoblastic Lymphadenopathy", "descriptor_ui": "D007119", "major_topic": true }, { "descriptor": "Lymphoma, T-Cell", "descriptor_ui": "D016399", "major_topic": true }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": false }, { "descriptor": "Pericardial Effusion", "descriptor_ui": "D010490", "major_topic": true }, { "descriptor": "rhoA GTP-Binding Protein", "descriptor_ui": "D020742", "major_topic": false } ], "publication": { "conference_name": null, "date": "2022 Jun 21", "date_precision": "day", "issue": "", "normalized_date": "2022-06-21", "pages": "", "proceedings_title": null, "publisher": "", "title": "Internal medicine (Tokyo, Japan)", "volume": "", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "A Case of Cardiac Tamponade as a Recurrence of Angioimmunoblastic T-Cell Lymphoma with the Detection of a p.Gly17Val RHOA Mutation in the Pericardial Effusion.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Many previous studies have reported the various proteins specifically secreted as inducers in the dorsal or ventral regions in vertebrate gastrula. However, little is known about the effect on cell fate of small molecules below 1000 Da. We therefore tried to identify small molecules specifically expressed in the dorsal marginal zone (DMZ) or ventral marginal zone (VMZ) in vertebrate gastrula. Small intracellular and secreted molecules were detected using explants and supernatant samples. Hydrophilic metabolites were analyzed by capillary ion chromatography-mass spectrometry and liquid chromatography-mass spectrometry, and lipids were analyzed by supercritical fluid chromatography-tandem mass spectrometry. In total, 190 hydrophilic metabolites and 396 lipids were identified. The DMZ was found to have high amounts of glycolysis- and glutathione metabolism-related metabolites in explants, and the VMZ was richer in purine metabolism-related metabolites. We also discovered some hydrophilic metabolites and lipids differentially contained in the DMZ or VMZ. Our research would contribute to a deeper understanding of the cellular physiology that regulates early embryogenesis.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yukako", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Ryosuke", "last_name": "Hayasaka", "name": null }, { "creator_type": "author", "first_name": "Masako", "last_name": "Hasebe", "name": null }, { "creator_type": "author", "first_name": "Satsuki", "last_name": "Ikeda", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Masaru", "last_name": "Tomita", "name": null }, { "creator_type": "author", "first_name": "Akiyoshi", "last_name": "Hirayama", "name": null }, { "creator_type": "author", "first_name": "Hiroki", "last_name": "Kuroda", "name": null } ], "identifiers": { "doi": { "normalized": "10.3390/metabo12060566" }, "pmcid": { "normalized": "PMC9229639" }, "pmid": { "normalized": "35736498" } }, "mesh": [], "publication": { "conference_name": null, "date": "2022 Jun 20", "date_precision": "day", "issue": "6", "normalized_date": "2022-06-20", "pages": "566", "proceedings_title": null, "publisher": "", "title": "Metabolites", "volume": "12", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Comparative Metabolomics of Small Molecules Specifically Expressed in the Dorsal or Ventral Marginal Zones in Vertebrate Gastrula.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "In living cells, chemical reactions are connected by sharing their products and substrates, and form complex systems, i.e. chemical reaction network. One of the largest missions in modern biology is to understand behaviors of such systems logically based on information of network structures. However, there are series of obstacles to study dynamical behaviors of complex network systems in biology. For example, network structure does not provide sufficient information to determine details of the dynamical behaviors. In this review, I will introduce a novel mathematical theory, structural sensitivity analysis, by which the responses of reaction systems upon the changes in enzyme activities/amounts are determined from network structure alone. The patterns of responses exhibit characteristic features, localization and hierarchy, depending on the topology of the network. The theory also shows that ranges of enzymatic regulations are governed by a mathematical law characterized by local topology of substructures. These findings imply that the network topology is one of the origins of biological robustness.", "classifications": [ { "id": "Mochizuki", "label": "Group Mochizuki", "parent": "Eiraku", "type": "group" }, { "id": "Eiraku", "label": "Team Eiraku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Atsushi", "last_name": "Mochizuki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1042/bcj20210545" }, "pmcid": { "normalized": "PMC9246345" }, "pmid": { "normalized": "35713414" } }, "mesh": [ { "descriptor": "Models, Biological", "descriptor_ui": "D008954", "major_topic": true } ], "publication": { "conference_name": null, "date": "2022 Jun 17", "date_precision": "day", "issue": "11", "normalized_date": "2022-06-17", "pages": "1265-1283", "proceedings_title": null, "publisher": "", "title": "The Biochemical journal", "volume": "479", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "A structural approach to understanding enzymatic regulation of chemical reaction networks.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The adult brain can flexibly adapt behaviors to specific life-stage demands. For example, while sexually naive male mice are aggressive to the conspecific young, they start to provide caregiving to infants around the time when their own young are expected. How such behavioral plasticity is implemented at the level of neural connections remains poorly understood. Here, using viral-genetic approaches, we establish hypothalamic oxytocin neurons as the key regulators of the parental caregiving behaviors of male mice. We then use rabies-virus-mediated unbiased screening to identify excitatory neural connections originating from the lateral hypothalamus to the oxytocin neurons to be drastically strengthened when male mice become fathers. These connections are functionally relevant, as their activation suppresses pup-directed aggression in virgin males. These results demonstrate the life-stage associated, long-distance, and cell-type-specific plasticity of neural connections in the hypothalamus, the brain region that is classically assumed to be hard-wired.", "classifications": [ { "id": "Miyamichi", "label": "Group Miyamichi", "parent": "Enomoto", "type": "group" }, { "id": "Enomoto", "label": "Team Enomoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Kengo", "last_name": "Inada", "name": null }, { "creator_type": "author", "first_name": "Mitsue", "last_name": "Hagihara", "name": null }, { "creator_type": "author", "first_name": "Kazuko", "last_name": "Tsujimoto", "name": null }, { "creator_type": "author", "first_name": "Takaya", "last_name": "Abe", "name": null }, { "creator_type": "author", "first_name": "Ayumu", "last_name": "Konno", "name": null }, { "creator_type": "author", "first_name": "Hirokazu", "last_name": "Hirai", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Kiyonari", "name": null }, { "creator_type": "author", "first_name": "Kazunari", "last_name": "Miyamichi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.neuron.2022.03.033" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "35443152" } }, "mesh": [ { "descriptor": "Aggression", "descriptor_ui": "D000374", "major_topic": true }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Hypothalamus", "descriptor_ui": "D007031", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Oxytocin", "descriptor_ui": "D010121", "major_topic": true }, { "descriptor": "Parents", "descriptor_ui": "D010290", "major_topic": false } ], "publication": { "conference_name": null, "date": "2022 Jun 15", "date_precision": "day", "issue": "12", "normalized_date": "2022-06-15", "pages": "2009-2023.e5", "proceedings_title": null, "publisher": "", "title": "Neuron", "volume": "110", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Plasticity of neural connections underlying oxytocin-mediated parental behaviors of male mice.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Cancer recurrence due to tumor cell quiescence after therapy and long-term remission is associated with cancer-related death. Previous studies have used cell models that are unable to return to a proliferative state; thus, the transition between quiescent and proliferative states is not well understood. Here, we report monolayer cancer cell models wherein the human non-small cell lung carcinoma cell line H2228 and pancreatic cancer cell line AsPC-1 can be reversibly induced to a quiescent state under hypoxic and serum-starved (HSS) conditions. Transcriptome and metabolome dual-omics profiles of these cells were compared with those of the human lung adenocarcinoma cell line A549, which was unable to enter a quiescent state under HSS conditions. The quiescence-inducible cells had substantially lower intracellular pyruvate and ATP levels in the quiescent state than in the proliferative state, and their response to sudden demand for energy was dramatically reduced. Furthermore, in quiescence-inducible cells, the transition between quiescent and proliferative states of these cells was regulated by the balance between the proliferation-promoting Ras and Rap1 signaling and the suppressive AGE/RAGE signaling. These cell models elucidate the transition between quiescent and proliferative states, allowing the development of drug-screening systems for quiescent tumor cells.", "classifications": [ { "id": "Kuchimaru", "label": "Group Kuchimaru", "parent": "Shintaku", "type": "group" }, { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" }, { "id": "Shintaku", "label": "Team Shintaku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Tetsuya", "last_name": "Kadonosono", "name": null }, { "creator_type": "author", "first_name": "Kotaro", "last_name": "Miyamoto", "name": null }, { "creator_type": "author", "first_name": "Shiori", "last_name": "Sakai", "name": null }, { "creator_type": "author", "first_name": "Yoshiyuki", "last_name": "Matsuo", "name": null }, { "creator_type": "author", "first_name": "Shojiro", "last_name": "Kitajima", "name": null }, { "creator_type": "author", "first_name": "Qiannan", "last_name": "Wang", "name": null }, { "creator_type": "author", "first_name": "Minori", "last_name": "Endo", "name": null }, { "creator_type": "author", "first_name": "Mizuho", "last_name": "Niibori", "name": null }, { "creator_type": "author", "first_name": "Takahiro", "last_name": "Kuchimaru", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Kiichi", "last_name": "Hirota", "name": null }, { "creator_type": "author", "first_name": "Shinae", "last_name": "Kizaka-Kondoh", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41598-022-14272-0" }, "pmcid": { "normalized": "PMC9198021" }, "pmid": { "normalized": "35701529" } }, "mesh": [ { "descriptor": "A549 Cells", "descriptor_ui": "D000072283", "major_topic": false }, { "descriptor": "Anaplastic Lymphoma Kinase", "descriptor_ui": "D000077548", "major_topic": true }, { "descriptor": "Antigens, Neoplasm", "descriptor_ui": "D000951", "major_topic": true }, { "descriptor": "Carcinoma, Non-Small-Cell Lung", "descriptor_ui": "D002289", "major_topic": true }, { "descriptor": "Cell Hypoxia", "descriptor_ui": "D015687", "major_topic": false }, { "descriptor": "Cell Proliferation", "descriptor_ui": "D049109", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Lung Neoplasms", "descriptor_ui": "D008175", "major_topic": true }, { "descriptor": "Mitogen-Activated Protein Kinases", "descriptor_ui": "D020928", "major_topic": true }, { "descriptor": "Neoplasm Recurrence, Local", "descriptor_ui": "D009364", "major_topic": false }, { "descriptor": "Pancreatic Neoplasms", "descriptor_ui": "D010190", "major_topic": true }, { "descriptor": "Receptor for Advanced Glycation End Products", "descriptor_ui": "D000067759", "major_topic": true }, { "descriptor": "Receptor Protein-Tyrosine Kinases", "descriptor_ui": "D020794", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false } ], "publication": { "conference_name": null, "date": "2022 Jun 14", "date_precision": "day", "issue": "1", "normalized_date": "2022-06-14", "pages": "9886", "proceedings_title": null, "publisher": "", "title": "Scientific reports", "volume": "12", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "AGE/RAGE axis regulates reversible transition to quiescent states of ALK-rearranged NSCLC and pancreatic cancer cells in monolayer cultures.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Enteroendocrine cells (EECs) are the primary sensory cells that sense the gut luminal environment and secret hormones to regulate organ function. Recent studies revealed that vagal afferent neurons are connected to EECs and relay sensory information from EECs to the brain stem. To date, however, the identity of vagal afferent neurons connected to a given EEC subtype and the mode of their gene responses to its intestinal hormone have remained unknown. Hypothesizing that EEC-associated vagal afferent neurons change their gene expression in response to the microbiota-related extracellular stimuli, we conducted comparative gene expression analyses of the nodose-petrosal ganglion complex (NPG) using specific pathogen-free (SPF) and germ-free (GF) mice. We report here that the Uts2b gene, which encodes a functionally unknown neuropeptide, urotensin 2B (UTS2B), is expressed in a microbiota-dependent manner in NPG neurons. In cultured NPG neurons, expression of Uts2b was induced by AR420626, the selective agonist for FFAR3. Moreover, distinct gastrointestinal hormones exerted differential effects on Uts2b expression in NPG neurons, where cholecystokinin (CCK) significantly increased its expression. The majority of Uts2b-expressing NPG neurons expressed CCK-A, the receptor for CCK, which comprised approximately 25% of all CCK-A-expressing NPG neurons. Selective fluorescent labeling of Uts2b-expressing NPG neurons revealed a direct contact of their nerve fibers to CCK-expressing EECs. This study identifies the Uts2b as a microbiota-regulated gene, demonstrates that Uts2b-expressing vagal afferent neurons transduce sensory information from CCK-expressing EECs to the brain, and suggests potential involvement of UTS2B in a modality of CCK actions.", "classifications": [ { "id": "Enomoto", "label": "Group Enomoto", "parent": "Enomoto", "type": "group" }, { "id": "Enomoto", "label": "Team Enomoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yuta", "last_name": "Yoshioka", "name": null }, { "creator_type": "author", "first_name": "Yoshihisa", "last_name": "Tachibana", "name": null }, { "creator_type": "author", "first_name": "Toshihiro", "last_name": "Uesaka", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Hioki", "name": null }, { "creator_type": "author", "first_name": "Yuya", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Takumi", "last_name": "Fukumoto", "name": null }, { "creator_type": "author", "first_name": "Hideki", "last_name": "Enomoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.bbrc.2022.03.117" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "35390674" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cholecystokinin", "descriptor_ui": "D002766", "major_topic": true }, { "descriptor": "Enteroendocrine Cells", "descriptor_ui": "D019858", "major_topic": false }, { "descriptor": "Intracellular Signaling Peptides and Proteins", "descriptor_ui": "D047908", "major_topic": true }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Microbiota", "descriptor_ui": "D064307", "major_topic": true }, { "descriptor": "Neurons, Afferent", "descriptor_ui": "D009475", "major_topic": true }, { "descriptor": "Nodose Ganglion", "descriptor_ui": "D009620", "major_topic": false }, { "descriptor": "Peptide Hormones", "descriptor_ui": "D036361", "major_topic": true }, { "descriptor": "Vagus Nerve", "descriptor_ui": "D014630", "major_topic": true } ], "publication": { "conference_name": null, "date": "2022 Jun 11", "date_precision": "day", "issue": "", "normalized_date": "2022-06-11", "pages": "66-72", "proceedings_title": null, "publisher": "", "title": "Biochemical and biophysical research communications", "volume": "608", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Uts2b is a microbiota-regulated gene expressed in vagal afferent neurons connected to enteroendocrine cells producing cholecystokinin.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "5-Aminolevulinic acid (5-ALA) is a natural amino acid and a precursor of heme and chlorophyll. Exogenously administered 5-ALA is metabolized into protoporphyrin IX (PpIX). PpIX accumulates in cancer cells because of the low activity of ferrochelatase, an enzyme that metabolizes PpIX to heme. High expression of 5-ALA influx transporters, such as peptide transporters 1/2, in cancer cells also enhances PpIX production. Because PpIX radiates red fluorescence when excited with blue/violet light, 5-ALA has been used for the visualization of various tumors. 5-ALA photodynamic diagnosis (PDD) has been shown to improve the tumor removal rate in high-grade gliomas and non-muscular invasive bladder cancers. However, 5-ALA PDD remains a challenge as a diagnostic method because tissue autofluorescence interferes with PpIX signals in cases where tumors emit only weak signals, and non-tumorous lesions, such as inflammatory sites, tend to emit PpIX fluorescence. Here, we review the current outline of 5-ALA PDD and strategies for improving its diagnostic applicability for tumor detection, focusing on optical techniques and 5-ALA metabolic pathways in both viable and necrotic tumor tissues.", "classifications": [ { "id": "Tanaka", "label": "Group Tanaka", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yoshinori", "last_name": "Harada", "name": null }, { "creator_type": "author", "first_name": "Yasutoshi", "last_name": "Murayama", "name": null }, { "creator_type": "author", "first_name": "Tetsuro", "last_name": "Takamatsu", "name": null }, { "creator_type": "author", "first_name": "Eigo", "last_name": "Otsuji", "name": null }, { "creator_type": "author", "first_name": "Hideo", "last_name": "Tanaka", "name": null } ], "identifiers": { "doi": { "normalized": "10.3390/ijms23126478" }, "pmcid": { "normalized": "PMC9223645" }, "pmid": { "normalized": "35742921" } }, "mesh": [ { "descriptor": "Aminolevulinic Acid", "descriptor_ui": "D000622", "major_topic": false }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Fluorescence", "descriptor_ui": "D005453", "major_topic": false }, { "descriptor": "Glioma", "descriptor_ui": "D005910", "major_topic": true }, { "descriptor": "Heme", "descriptor_ui": "D006418", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Optical Imaging", "descriptor_ui": "D061848", "major_topic": false }, { "descriptor": "Photochemotherapy", "descriptor_ui": "D010778", "major_topic": true }, { "descriptor": "Photosensitizing Agents", "descriptor_ui": "D017319", "major_topic": false }, { "descriptor": "Protoporphyrins", "descriptor_ui": "D011524", "major_topic": false }, { "descriptor": "Radiopharmaceuticals", "descriptor_ui": "D019275", "major_topic": false } ], "publication": { "conference_name": null, "date": "2022 Jun 9", "date_precision": "day", "issue": "12", "normalized_date": "2022-06-09", "pages": "6478", "proceedings_title": null, "publisher": "", "title": "International journal of molecular sciences", "volume": "23", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "5-Aminolevulinic Acid-Induced Protoporphyrin IX Fluorescence Imaging for Tumor Detection: Recent Advances and Challenges.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Protein methylation occurs predominantly on lysine and arginine residues, but histidine also serves as a methylation substrate. However, a limited number of enzymes responsible for this modification have been reported. Moreover, the biological role of histidine methylation has remained poorly understood to date. Here, we report that human METTL18 is a histidine methyltransferase for the ribosomal protein RPL3 and that the modification specifically slows ribosome traversal on Tyr codons, allowing the proper folding of synthesized proteins. By performing an in vitro methylation assay with a methyl donor analog and quantitative mass spectrometry, we found that His245 of RPL3 is methylated at the tau-N position by METTL18. Structural comparison of the modified and unmodified ribosomes showed stoichiometric modification and suggested a role in translation reactions. Indeed, genome-wide ribosome profiling and an in vitro translation assay revealed that translation elongation at Tyr codons was suppressed by RPL3 methylation. Because the slower elongation provides enough time for nascent protein folding, RPL3 methylation protects cells from the cellular aggregation of Tyr-rich proteins. Our results reveal histidine methylation as an example of a ribosome modification that ensures proteome integrity in cells.", "classifications": [ { "id": "Sodeoka", "label": "Group Sodeoka", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Eriko", "last_name": "Matsuura-Suzuki", "name": null }, { "creator_type": "author", "first_name": "Tadahiro", "last_name": "Shimazu", "name": null }, { "creator_type": "author", "first_name": "Mari", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Kaoru", "last_name": "Kotoshiba", "name": null }, { "creator_type": "author", "first_name": "Takehiro", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Kazuhiro", "last_name": "Kashiwagi", "name": null }, { "creator_type": "author", "first_name": "Yoshihiro", "last_name": "Sohtome", "name": null }, { "creator_type": "author", "first_name": "Mai", "last_name": "Akakabe", "name": null }, { "creator_type": "author", "first_name": "Mikiko", "last_name": "Sodeoka", "name": null }, { "creator_type": "author", "first_name": "Naoshi", "last_name": "Dohmae", "name": null }, { "creator_type": "author", "first_name": "Takuhiro", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Yoichi", "last_name": "Shinkai", "name": null }, { "creator_type": "author", "first_name": "Shintaro", "last_name": "Iwasaki", "name": null } ], "identifiers": { "doi": { "normalized": "10.7554/elife.72780" }, "pmcid": { "normalized": "PMC9177149" }, "pmid": { "normalized": "35674491" } }, "mesh": [ { "descriptor": "Histidine", "descriptor_ui": "D006639", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Methylation", "descriptor_ui": "D008745", "major_topic": false }, { "descriptor": "Methyltransferases", "descriptor_ui": "D008780", "major_topic": true }, { "descriptor": "Protein Biosynthesis", "descriptor_ui": "D014176", "major_topic": false }, { "descriptor": "Proteostasis", "descriptor_ui": "D000074702", "major_topic": true }, { "descriptor": "Ribosomal Protein L3", "descriptor_ui": "D000090822", "major_topic": true } ], "publication": { "conference_name": null, "date": "2022 Jun 8", "date_precision": "day", "issue": "", "normalized_date": "2022-06-08", "pages": "e72780", "proceedings_title": null, "publisher": "", "title": "eLife", "volume": "11", "year": 2022 }, "ssbd": { "database": [ "ssbd-database-000277" ], "repository": [ "ssbd-repos-000277" ] }, "title": "METTL18-mediated histidine methylation of RPL3 modulates translation elongation for proteostasis maintenance.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "To improve the performance of assisted reproductive technology, it is necessary to find an indicator that can identify and select embryos that will be born or be aborted. We searched for indicators of embryo selection by comparing born/abort mouse embryos. We found that asynchronous embryos during the 4-8-cell stage were predisposed to be aborted. In asynchronous mouse embryos, the nuclear translocation of YAP1 in some blastomeres and compaction were delayed, and the number of ICMs was reduced. Hence, it is possible that asynchronous embryos have abnormal differentiation. When the synchrony of human embryos was observed, it was confirmed that embryos that did not reach clinical pregnancy had asynchrony as in mice. This could make synchrony a universal indicator common to all animal species.", "classifications": [ { "id": "JPMJCR1927", "label": "JPMJCR1927", "researcher": "Yuichi Wakamoto", "type": "grant" }, { "id": "Kobayashi", "label": "Group Kobayashi", "parent": "Wakamoto", "type": "group" }, { "id": "Wakamoto", "label": "Group Wakamoto", "parent": "Wakamoto", "type": "group" }, { "id": "Wakamoto", "label": "Team Wakamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Daisuke", "last_name": "Mashiko", "name": null }, { "creator_type": "author", "first_name": "Zenki", "last_name": "Ikeda", "name": null }, { "creator_type": "author", "first_name": "Mikiko", "last_name": "Tokoro", "name": null }, { "creator_type": "author", "first_name": "Yu", "last_name": "Hatano", "name": null }, { "creator_type": "author", "first_name": "Tatsuma", "last_name": "Yao", "name": null }, { "creator_type": "author", "first_name": "Tetsuya J.", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Noritaka", "last_name": "Fukunaga", "name": null }, { "creator_type": "author", "first_name": "Yoshimasa", "last_name": "Asada", "name": null }, { "creator_type": "author", "first_name": "Kazuo", "last_name": "Yamagata", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41598-022-13646-8" }, "pmcid": { "normalized": "PMC9174281" }, "pmid": { "normalized": "35672442" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Blastocyst", "descriptor_ui": "D001755", "major_topic": false }, { "descriptor": "Blastomeres", "descriptor_ui": "D001757", "major_topic": false }, { "descriptor": "Embryo, Mammalian", "descriptor_ui": "D004622", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Live Birth", "descriptor_ui": "D050498", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Pregnancy", "descriptor_ui": "D011247", "major_topic": false }, { "descriptor": "Preimplantation Diagnosis", "descriptor_ui": "D019836", "major_topic": true } ], "publication": { "conference_name": null, "date": "2022 Jun 7", "date_precision": "day", "issue": "1", "normalized_date": "2022-06-07", "pages": "9411", "proceedings_title": null, "publisher": "", "title": "Scientific reports", "volume": "12", "year": 2022 }, "ssbd": { "database": [ "ssbd-database-000284" ], "repository": [ "ssbd-repos-000284" ] }, "title": "Asynchronous division at 4-8-cell stage of preimplantation embryos affects live birth through ICM/TE differentiation.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The prevalence of NTRK fusions in non-small cell carcinoma (NSCLC) is only approximately 0.2%, most of which harbor NTRK1 fusions. NSCLCs with NTRK3 fusions are extremely rare. Herein, we report a case of low-grade tracheal adenocarcinoma in a 64-year-old woman. Histologically, areas of complicated tubule-papillary or cribriform patterns constituted a major component of the tumor and comprised cuboidal to columnar epithelial tumor cells with pale eosinophilic cytoplasm and cytoplasmic mucin, similar to subsets of sinonasal low-grade non-intestinal-type adenocarcinomas. Immunohistochemically, the tumor was positive for MUC5AC and MUC4 and showed nuclear expression of the pan-Trk antibody. ETV6::NTRK3 was identified by reverse transcription-polymerase chain reaction using formalin-fixed paraffin-embedded tissues. To the best of our knowledge, this is the first case of low-grade tracheal adenocarcinoma with ETV6::NTRK3 fusion. Our case illustrates that low-grade adenocarcinomas with ETV6::NTRK3 fusion may exist throughout the respiratory tract.", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Satsuki", "last_name": "Kishikawa", "name": null }, { "creator_type": "author", "first_name": "Takuo", "last_name": "Hayashi", "name": null }, { "creator_type": "author", "first_name": "Junzo", "last_name": "Shimizu", "name": null }, { "creator_type": "author", "first_name": "Bungo", "last_name": "Fuwa", "name": null }, { "creator_type": "author", "first_name": "Akitaka", "last_name": "Nonomura", "name": null }, { "creator_type": "author", "first_name": "Tsuyoshi", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Yao", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/s00428-022-03353-0" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "35670854" } }, "mesh": [ { "descriptor": "Adenocarcinoma", "descriptor_ui": "D000230", "major_topic": true }, { "descriptor": "Biomarkers, Tumor", "descriptor_ui": "D014408", "major_topic": false }, { "descriptor": "Carcinoma", "descriptor_ui": "D002277", "major_topic": true }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Immunohistochemistry", "descriptor_ui": "D007150", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Oncogene Proteins, Fusion", "descriptor_ui": "D015514", "major_topic": false }, { "descriptor": "Proto-Oncogene Proteins c-ets", "descriptor_ui": "D050783", "major_topic": false }, { "descriptor": "Repressor Proteins", "descriptor_ui": "D012097", "major_topic": false } ], "publication": { "conference_name": null, "date": "2022 Jun 7", "date_precision": "day", "issue": "", "normalized_date": "2022-06-07", "pages": "", "proceedings_title": null, "publisher": "", "title": "Virchows Archiv : an international journal of pathology", "volume": "", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Low-grade tracheal adenocarcinoma with ETV6::NTRK3 fusion: unique morphology akin to subsets of sinonasal low-grade non-intestinal-type adenocarcinoma.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Pattern dynamics on curved surfaces are found everywhere in nature. The geometry of surfaces has been shown to influence dynamics and play a functional role, yet a comprehensive understanding is still elusive. Here, we report for the first time that a static Turing pattern on a flat surface can propagate on a curved surface, as opposed to previous studies, where the pattern is presupposed to be static irrespective of the surface geometry. To understand such significant changes on curved surfaces, we investigate reaction-diffusion systems on axisymmetric curved surfaces. Numerical and theoretical analyses reveal that both the symmetries of the surface and pattern participate in the initiation of pattern propagation. This study provides a novel and generic mechanism of pattern propagation that is caused by surface curvature, as well as insights into the general role of surface geometry.", "classifications": [ { "id": "Ishihara", "label": "Group Ishihara", "parent": "Sawai", "type": "group" }, { "id": "Sawai", "label": "Team Sawai", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Ryosuke", "last_name": "Nishide", "name": null }, { "creator_type": "author", "first_name": "Shuji", "last_name": "Ishihara", "name": null } ], "identifiers": { "doi": { "normalized": "10.1103/physrevlett.128.224101" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "35714259" } }, "mesh": [ { "descriptor": "Diffusion", "descriptor_ui": "D004058", "major_topic": false }, { "descriptor": "Models, Theoretical", "descriptor_ui": "D008962", "major_topic": true } ], "publication": { "conference_name": null, "date": "2022 Jun 3", "date_precision": "day", "issue": "22", "normalized_date": "2022-06-03", "pages": "224101", "proceedings_title": null, "publisher": "", "title": "Physical review letters", "volume": "128", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Pattern Propagation Driven by Surface Curvature.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Dynamic chromatin behavior plays a critical role in various genome functions. However, it remains unclear how chromatin behavior changes during interphase, where the nucleus enlarges and genomic DNA doubles. While the previously reported chromatin movements varied during interphase when measured using a minute or longer time scale, we unveil that local chromatin motion captured by single-nucleosome imaging/tracking on a second time scale remained steady throughout G1, S, and G2 phases in live human cells. This motion mode appeared to change beyond this time scale. A defined genomic region also behaved similarly. Combined with Brownian dynamics modeling, our results suggest that this steady-state chromatin motion was mainly driven by thermal fluctuations. Steady-state motion temporarily increased following a DNA damage response. Our findings support the viscoelastic properties of chromatin. We propose that the observed steady-state chromatin motion allows cells to conduct housekeeping functions, such as transcription and DNA replication, under similar environments during interphase.", "classifications": [ { "id": "Onami", "label": "Group Onami", "parent": "Fujiwara", "type": "group" }, { "id": "Fujiwara", "label": "Team Fujiwara", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Shiori", "last_name": "Iida", "name": null }, { "creator_type": "author", "first_name": "Soya", "last_name": "Shinkai", "name": null }, { "creator_type": "author", "first_name": "Yuji", "last_name": "Itoh", "name": null }, { "creator_type": "author", "first_name": "Sachiko", "last_name": "Tamura", "name": null }, { "creator_type": "author", "first_name": "Masato T.", "last_name": "Kanemaki", "name": null }, { "creator_type": "author", "first_name": "Shuichi", "last_name": "Onami", "name": null }, { "creator_type": "author", "first_name": "Kazuhiro", "last_name": "Maeshima", "name": null } ], "identifiers": { "doi": { "normalized": "10.1126/sciadv.abn5626" }, "pmcid": { "normalized": "PMC9166292" }, "pmid": { "normalized": "35658044" } }, "mesh": [ { "descriptor": "Cell Nucleus", "descriptor_ui": "D002467", "major_topic": false }, { "descriptor": "Chromatin", "descriptor_ui": "D002843", "major_topic": true }, { "descriptor": "DNA Replication", "descriptor_ui": "D004261", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Interphase", "descriptor_ui": "D007399", "major_topic": false }, { "descriptor": "Nucleosomes", "descriptor_ui": "D009707", "major_topic": true } ], "publication": { "conference_name": null, "date": "2022 Jun 3", "date_precision": "day", "issue": "22", "normalized_date": "2022-06-03", "pages": "eabn5626", "proceedings_title": null, "publisher": "", "title": "Science advances", "volume": "8", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Single-nucleosome imaging reveals steady-state motion of interphase chromatin in living human cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Analyzing only one cell allows the changes and characteristics of intracellular metabolites during the chromosome segregation process to be precisely captured and mitotic sub-phases to be dissected at the metabolite level.", "classifications": [ { "id": "Higaki", "label": "Group Higaki", "parent": "Ueda", "type": "group" }, { "id": "Ueda", "label": "Team Ueda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Emiko", "last_name": "Okubo-Kurihara", "name": null }, { "creator_type": "author", "first_name": "Ahmed", "last_name": "Ali", "name": null }, { "creator_type": "author", "first_name": "Mika", "last_name": "Hiramoto", "name": null }, { "creator_type": "author", "first_name": "Yukio", "last_name": "Kurihara", "name": null }, { "creator_type": "author", "first_name": "Yasmine", "last_name": "Abouleila", "name": null }, { "creator_type": "author", "first_name": "Eman Muhammad", "last_name": "Abdelazem", "name": null }, { "creator_type": "author", "first_name": "Takayuki", "last_name": "Kawai", "name": null }, { "creator_type": "author", "first_name": "Yuko", "last_name": "Makita", "name": null }, { "creator_type": "author", "first_name": "Mika", "last_name": "Kawashima", "name": null }, { "creator_type": "author", "first_name": "Tsuyoshi", "last_name": "Esaki", "name": null }, { "creator_type": "author", "first_name": "Hiroaki", "last_name": "Shimada", "name": null }, { "creator_type": "author", "first_name": "Tetsuya", "last_name": "Mori", "name": null }, { "creator_type": "author", "first_name": "Masami Yokota", "last_name": "Hirai", "name": null }, { "creator_type": "author", "first_name": "Takumi", "last_name": "Higaki", "name": null }, { "creator_type": "author", "first_name": "Seiichiro", "last_name": "Hasezawa", "name": null }, { "creator_type": "author", "first_name": "Yoshihiro", "last_name": "Shimizu", "name": null }, { "creator_type": "author", "first_name": "Tsutomu", "last_name": "Masujima", "name": null }, { "creator_type": "author", "first_name": "Minami", "last_name": "Matsui", "name": null } ], "identifiers": { "doi": { "normalized": "10.1093/plphys/kiac093" }, "pmcid": { "normalized": "PMC9157120" }, "pmid": { "normalized": "35301535" } }, "mesh": [ { "descriptor": "Chromosome Segregation", "descriptor_ui": "D020090", "major_topic": true }, { "descriptor": "Mitosis", "descriptor_ui": "D008938", "major_topic": true } ], "publication": { "conference_name": null, "date": "2022 Jun 1", "date_precision": "day", "issue": "2", "normalized_date": "2022-06-01", "pages": "459-464", "proceedings_title": null, "publisher": "", "title": "Plant physiology", "volume": "189", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Tracking metabolites at single-cell resolution reveals metabolic dynamics during plant mitosis.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Objective Graft failure (GF) is a life-threatening complication of hematopoietic stem cell transplantation (HSCT). A standardized conditioning regimen and an appropriate graft source of salvage HSCT for GF have not yet been established. Some case series have shown good hematopoietic recoveries after salvage HSCT using a short-term reduced-intensity preparative regimen consisting of fludarabine (30-90 mg/m(2)), cyclophosphamide (2 g/m(2)), and total-body irradiation (2 Gy). However, the dose of fludarabine has varied in these reports based on the clinical condition of the patients, resulting in very limited experiences with each dose of fludarabine. Methods We retrospectively analyzed 10 patients who developed GF after allogeneic HSCT and underwent salvage cord blood transplantation (CBT) using the above-mentioned conditioning regimen with a fixed dose (90 mg/m(2)) of fludarabine. Results Eight patients (80.0%) achieved neutrophil engraftment within 30 days from salvage HSCT with a median of 21 (range, 17-23) days. The 1-year overall survival (OS) rate after the salvage HSCT was 50.0%, and the median OS was 281 (range, 23-1,638) days. Cumulative incidences of non-relapse mortality and relapse at 1 year were 50.0% and 10.0%, respectively. Conclusion CBT using this short-term reduced-intensity conditioning regimen may be a promising salvage therapy for GF.", "classifications": [ { "id": "Nishikii", "label": "Group Nishikii", "parent": "Shintaku", "type": "group" }, { "id": "Shintaku", "label": "Team Shintaku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Sakurako", "last_name": "Suma", "name": null }, { "creator_type": "author", "first_name": "Yasuhisa", "last_name": "Yokoyama", "name": null }, { "creator_type": "author", "first_name": "Haruka", "last_name": "Momose", "name": null }, { "creator_type": "author", "first_name": "Kenichi", "last_name": "Makishima", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Kiyoki", "name": null }, { "creator_type": "author", "first_name": "Tatsuhiro", "last_name": "Sakamoto", "name": null }, { "creator_type": "author", "first_name": "Manabu", "last_name": "Kusakabe", "name": null }, { "creator_type": "author", "first_name": "Takayasu", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Naoki", "last_name": "Kurita", "name": null }, { "creator_type": "author", "first_name": "Hidekazu", "last_name": "Nishikii", "name": null }, { "creator_type": "author", "first_name": "Mamiko", "last_name": "Sakata-Yanagimoto", "name": null }, { "creator_type": "author", "first_name": "Naoshi", "last_name": "Obara", "name": null }, { "creator_type": "author", "first_name": "Yuichi", "last_name": "Hasegawa", "name": null }, { "creator_type": "author", "first_name": "Shigeru", "last_name": "Chiba", "name": null } ], "identifiers": { "doi": { "normalized": "10.2169/internalmedicine.7836-21" }, "pmcid": { "normalized": "PMC9259308" }, "pmid": { "normalized": "34803091" } }, "mesh": [ { "descriptor": "Cord Blood Stem Cell Transplantation", "descriptor_ui": "D036101", "major_topic": true }, { "descriptor": "Graft vs Host Disease", "descriptor_ui": "D006086", "major_topic": true }, { "descriptor": "Hematopoietic Stem Cell Transplantation", "descriptor_ui": "D018380", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Retrospective Studies", "descriptor_ui": "D012189", "major_topic": false }, { "descriptor": "Salvage Therapy", "descriptor_ui": "D016879", "major_topic": false }, { "descriptor": "Transplantation Conditioning", "descriptor_ui": "D019172", "major_topic": false }, { "descriptor": "Vidarabine", "descriptor_ui": "D014740", "major_topic": false } ], "publication": { "conference_name": null, "date": "2022 Jun 1", "date_precision": "day", "issue": "11", "normalized_date": "2022-06-01", "pages": "1673-1679", "proceedings_title": null, "publisher": "", "title": "Internal medicine (Tokyo, Japan)", "volume": "61", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Salvage Cord Blood Transplantation Using a Short-term Reduced-intensity Conditioning Regimen for Graft Failure.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Download figureDownload PowerPoint", "classifications": [ { "id": "Nishida", "label": "Group Nishida", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yasunori", "last_name": "Iwata", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Nakade", "name": null }, { "creator_type": "author", "first_name": "Shinji", "last_name": "Kitajima", "name": null }, { "creator_type": "author", "first_name": "Shiori", "last_name": "Yoneda-Nakagawa", "name": null }, { "creator_type": "author", "first_name": "Megumi", "last_name": "Oshima", "name": null }, { "creator_type": "author", "first_name": "Norihiko", "last_name": "Sakai", "name": null }, { "creator_type": "author", "first_name": "Hisayuki", "last_name": "Ogura", "name": null }, { "creator_type": "author", "first_name": "Koichi", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Tadashi", "last_name": "Toyama", "name": null }, { "creator_type": "author", "first_name": "Yuta", "last_name": "Yamamura", "name": null }, { "creator_type": "author", "first_name": "Taro", "last_name": "Miyagawa", "name": null }, { "creator_type": "author", "first_name": "Hiroka", "last_name": "Yamazaki", "name": null }, { "creator_type": "author", "first_name": "Akinori", "last_name": "Hara", "name": null }, { "creator_type": "author", "first_name": "Miho", "last_name": "Shimizu", "name": null }, { "creator_type": "author", "first_name": "Kengo", "last_name": "Furuichi", "name": null }, { "creator_type": "author", "first_name": "Masashi", "last_name": "Mita", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Hamase", "name": null }, { "creator_type": "author", "first_name": "Tomohiro", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Motohiro", "last_name": "Nishida", "name": null }, { "creator_type": "author", "first_name": "Wataru", "last_name": "Muramatsu", "name": null }, { "creator_type": "author", "first_name": "Hisashi", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Shigeyuki", "last_name": "Shichino", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Ueha", "name": null }, { "creator_type": "author", "first_name": "Kouji", "last_name": "Matsushima", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Wada", "name": null } ], "identifiers": { "doi": { "normalized": "10.1152/ajprenal.00198.2021" }, "pmcid": { "normalized": null }, "pmid": { "normalized": null } }, "mesh": [], "publication": { "conference_name": null, "date": "2022-06", "date_precision": "month", "issue": "6", "normalized_date": "2022-06", "pages": "F667-F679", "proceedings_title": null, "publisher": "American Physiological Society", "title": "American Journal of Physiology-Renal Physiology", "volume": "322", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Protective effect of d-alanine against acute kidney injury", "url": "https://journals.physiology.org/doi/full/10.1152/ajprenal.00198.2021", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The development of an in vitro cell model that can be used to study severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) research is expected. Here we conducted infection experiments in bronchial organoids (BO) and an BO-derived air-liquid interface model (BO-ALI) using 8 SARS-CoV-2 variants. The infection efficiency in BO-ALI was more than 1,000 times higher than that in BO. Among the bronchial epithelial cells, we found that ciliated cells were infected with the virus, but basal cells were not. Ciliated cells died 7 days after the viral infection, but basal cells survived after the viral infection and differentiated into ciliated cells. Fibroblast growth factor 10 signaling was essential for this differentiation. These results indicate that BO and BO-ALI may be used not only to evaluate the cell response to SARS-CoV-2 and coronavirus disease 2019 (COVID-19) therapeutic agents, but also for airway regeneration studies.", "classifications": [ { "id": "Yamamoto", "label": "Group Yamamoto", "parent": "Toyoshima", "type": "group" }, { "id": "Toyoshima", "label": "Team Toyoshima", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Emi", "last_name": "Sano", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Rina", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Yumi", "last_name": "Itoh", "name": null }, { "creator_type": "author", "first_name": "Ayaka", "last_name": "Sakamoto", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Sakai", "name": null }, { "creator_type": "author", "first_name": "Akatsuki", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Okuzaki", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Motooka", "name": null }, { "creator_type": "author", "first_name": "Yukiko", "last_name": "Muramoto", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Noda", "name": null }, { "creator_type": "author", "first_name": "Tomohiko", "last_name": "Takasaki", "name": null }, { "creator_type": "author", "first_name": "Jun-Ichi", "last_name": "Sakuragi", "name": null }, { "creator_type": "author", "first_name": "Shohei", "last_name": "Minami", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Yasufumi", "last_name": "Matsumura", "name": null }, { "creator_type": "author", "first_name": "Miki", "last_name": "Nagao", "name": null }, { "creator_type": "author", "first_name": "Toru", "last_name": "Okamoto", "name": null }, { "creator_type": "author", "first_name": "Kazuo", "last_name": "Takayama", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s42003-022-03499-2" }, "pmcid": { "normalized": "PMC9151746" }, "pmid": { "normalized": "35637255" } }, "mesh": [ { "descriptor": "Bronchi", "descriptor_ui": "D001980", "major_topic": false }, { "descriptor": "COVID-19", "descriptor_ui": "D000086382", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Organoids", "descriptor_ui": "D009940", "major_topic": false }, { "descriptor": "SARS-CoV-2", "descriptor_ui": "D000086402", "major_topic": true } ], "publication": { "conference_name": null, "date": "2022 May 30", "date_precision": "day", "issue": "1", "normalized_date": "2022-05-30", "pages": "516", "proceedings_title": null, "publisher": "", "title": "Communications biology", "volume": "5", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Cell response analysis in SARS-CoV-2 infected bronchial organoids.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Brown adipose tissue (BAT) is a metabolically active organ that contributes to the thermogenic response to cold exposure. In addition, other thermogenic cells termed beige adipocytes are generated in white adipose tissue (WAT) by cold exposure. Although activation of brown/beige adipose tissue is associated with mobilization of both glucose and lipids, few studies have focused on the role of glycolytic enzymes in regulating adipose tissue function. We generated mouse models with specific deletion of the glycolytic enzyme phosphoglycerate mutase 1 (PGAM1) from adipose tissue. Deletion of Pgam1 from both BAT and WAT promoted whitening of BAT with beiging of visceral WAT, whereas deletion of Pgam1 from BAT alone led to whitening of BAT without beiging of WAT. Our results demonstrate a potential role of glycolytic enzymes in beiging of visceral WAT and suggest that PGAM1 would be a novel therapeutic target in obesity and diabetes.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yohko", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Ippei", "last_name": "Shimizu", "name": null }, { "creator_type": "author", "first_name": "Yung-Ting", "last_name": "Hsiao", "name": null }, { "creator_type": "author", "first_name": "Masayoshi", "last_name": "Suda", "name": null }, { "creator_type": "author", "first_name": "Goro", "last_name": "Katsuumi", "name": null }, { "creator_type": "author", "first_name": "Masahide", "last_name": "Seki", "name": null }, { "creator_type": "author", "first_name": "Yutaka", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Shujiro", "last_name": "Okuda", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Tohru", "last_name": "Minamino", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.isci.2022.104268" }, "pmcid": { "normalized": "PMC9065309" }, "pmid": { "normalized": "35521515" } }, "mesh": [], "publication": { "conference_name": null, "date": "2022 May 20", "date_precision": "day", "issue": "5", "normalized_date": "2022-05-20", "pages": "104268", "proceedings_title": null, "publisher": "", "title": "iScience", "volume": "25", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Differing impact of phosphoglycerate mutase 1-deficiency on brown and white adipose tissue.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Insulin signaling promotes anabolic metabolism to regulate cell growth through multi-omic interactions. To obtain a comprehensive view of the cellular responses to insulin, we constructed a trans-omic network of insulin action in Drosophila cells that involves the integration of multi-omic data sets. In this network, 14 transcription factors, including Myc, coordinately upregulate the gene expression of anabolic processes such as nucleotide synthesis, transcription, and translation, consistent with decreases in metabolites such as nucleotide triphosphates and proteinogenic amino acids required for transcription and translation. Next, as cell growth is required for cell proliferation and insulin can stimulate proliferation in a context-dependent manner, we integrated the trans-omic network with results from a CRISPR functional screen for cell proliferation. This analysis validates the role of a Myc-mediated subnetwork that coordinates the activation of genes involved in anabolic processes required for cell growth.", "classifications": [ { "id": "JPMJCR2123", "label": "JPMJCR2123", "researcher": "Shinya Kuroda", "type": "grant" }, { "id": "Kuroda", "label": "Group Kuroda", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Akira", "last_name": "Terakawa", "name": null }, { "creator_type": "author", "first_name": "Yanhui", "last_name": "Hu", "name": null }, { "creator_type": "author", "first_name": "Toshiya", "last_name": "Kokaji", "name": null }, { "creator_type": "author", "first_name": "Katsuyuki", "last_name": "Yugi", "name": null }, { "creator_type": "author", "first_name": "Keigo", "last_name": "Morita", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Ohno", "name": null }, { "creator_type": "author", "first_name": "Yifei", "last_name": "Pan", "name": null }, { "creator_type": "author", "first_name": "Yunfan", "last_name": "Bai", "name": null }, { "creator_type": "author", "first_name": "Andrey A.", "last_name": "Parkhitko", "name": null }, { "creator_type": "author", "first_name": "Xiaochun", "last_name": "Ni", "name": null }, { "creator_type": "author", "first_name": "John M.", "last_name": "Asara", "name": null }, { "creator_type": "author", "first_name": "Martha L.", "last_name": "Bulyk", "name": null }, { "creator_type": "author", "first_name": "Norbert", "last_name": "Perrimon", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Kuroda", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.isci.2022.104231" }, "pmcid": { "normalized": "PMC9044165" }, "pmid": { "normalized": "35494245" } }, "mesh": [], "publication": { "conference_name": null, "date": "2022 May 20", "date_precision": "day", "issue": "5", "normalized_date": "2022-05-20", "pages": "104231", "proceedings_title": null, "publisher": "", "title": "iScience", "volume": "25", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Trans-omics analysis of insulin action reveals a cell growth subnetwork which co-regulates anabolic processes.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The effects of transcription factors on the maintenance and differentiation of human-induced or embryonic pluripotent stem cells (iPSCs/ESCs) have been well studied. However, the importance of posttranscriptional regulatory mechanisms, which cause the quantitative dissociation of mRNA and protein expression, has not been explored in detail. Here, by combining transcriptome and proteome profiling, we identified 228 posttranscriptionally regulated genes with strict upregulation of the protein level in iPSCs/ESCs. Among them, we found 84 genes were vital for the survival of iPSCs and HDFs, including 20 genes that were specifically necessary for iPSC survival. These 20 proteins were upregulated only in iPSCs/ESCs and not in differentiated cells derived from the three germ layers. Although there are still unknown mechanisms that downregulate protein levels in HDFs, these results reveal that posttranscriptionally regulated genes have a crucial role in iPSC survival.", "classifications": [ { "id": "Yamamoto", "label": "Group Yamamoto", "parent": "Toyoshima", "type": "group" }, { "id": "Toyoshima", "label": "Team Toyoshima", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Mio", "last_name": "Iwasaki", "name": null }, { "creator_type": "author", "first_name": "Yuka", "last_name": "Kawahara", "name": null }, { "creator_type": "author", "first_name": "Chikako", "last_name": "Okubo", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Yamakawa", "name": null }, { "creator_type": "author", "first_name": "Michiko", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Tsuyoshi", "last_name": "Tabata", "name": null }, { "creator_type": "author", "first_name": "Yohei", "last_name": "Nishi", "name": null }, { "creator_type": "author", "first_name": "Megumi", "last_name": "Narita", "name": null }, { "creator_type": "author", "first_name": "Akira", "last_name": "Ohta", "name": null }, { "creator_type": "author", "first_name": "Hirohide", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Masato", "last_name": "Nakagawa", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Yamanaka", "name": null }, { "creator_type": "author", "first_name": "Kazutoshi", "last_name": "Takahashi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.isci.2022.104289" }, "pmcid": { "normalized": "PMC9097716" }, "pmid": { "normalized": "35573189" } }, "mesh": [], "publication": { "conference_name": null, "date": "2022 May 20", "date_precision": "day", "issue": "5", "normalized_date": "2022-05-20", "pages": "104289", "proceedings_title": null, "publisher": "", "title": "iScience", "volume": "25", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Multi-omics approach reveals posttranscriptionally regulated genes are essential for human pluripotent stem cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "We investigated the effects of glutathione trisulfide (GSSSG) on lipopolysaccharide (LPS)-induced inflammatory gene expression in immortalized ARPE-19, and primary human and mouse retinal pigment epithelial (RPE) cells. Sulfane sulfur molecules were significantly increased in GSSSG-treated ARPE-19 cells. GSSSG prevented the LPS-induced upregulation of interleukin (IL)-1beta, IL-6, and C-C motif chemokine ligand 2 (CCL2) in ARPE-19/primary RPE cells. Moreover, GSSSG prevented the activation of the nuclear factor-kappa B p65 subunit, and promoted the activation of extracellular signal-regulated kinase 1/2 (ERK1/2) in LPS-treated ARPE-19 cells. ERK1/2 inhibition prevented the GSSSG-mediated inhibition of LPS-induced IL-6 and CCL2 upregulation. Additionally, ERK1/2 activation prevented the upregulation of these genes in the absence of GSSSG. Knockdown of HMOX1 or NRF2, known as anti-oxidative genes, did not affect the activity of GSSSG in the context of LPS stimulation. These findings suggest that GSSSG attenuates LPS-induced inflammatory gene expression via ERK signaling hyperactivation, independently of the NRF2/HMOX1 pathway.", "classifications": [ { "id": "Akaike", "label": "Group Akaike", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Tawarayama", "name": null }, { "creator_type": "author", "first_name": "Noriyuki", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Maki", "last_name": "Inoue-Yanagimachi", "name": null }, { "creator_type": "author", "first_name": "Noriko", "last_name": "Himori", "name": null }, { "creator_type": "author", "first_name": "Satoru", "last_name": "Tsuda", "name": null }, { "creator_type": "author", "first_name": "Kota", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Tomoaki", "last_name": "Ida", "name": null }, { "creator_type": "author", "first_name": "Takaaki", "last_name": "Akaike", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Kunikata", "name": null }, { "creator_type": "author", "first_name": "Toru", "last_name": "Nakazawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1080/09273948.2020.1833224" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "33215957" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Epithelial Cells", "descriptor_ui": "D004847", "major_topic": false }, { "descriptor": "Gene Expression", "descriptor_ui": "D015870", "major_topic": false }, { "descriptor": "Glutathione", "descriptor_ui": "D005978", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Inflammation", "descriptor_ui": "D007249", "major_topic": false }, { "descriptor": "Interleukin-6", "descriptor_ui": "D015850", "major_topic": false }, { "descriptor": "Lipopolysaccharides", "descriptor_ui": "D008070", "major_topic": true }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "NF-E2-Related Factor 2", "descriptor_ui": "D051267", "major_topic": false }, { "descriptor": "Retinal Pigment Epithelium", "descriptor_ui": "D055213", "major_topic": true }, { "descriptor": "Retinal Pigments", "descriptor_ui": "D012168", "major_topic": false }, { "descriptor": "Sulfur", "descriptor_ui": "D013455", "major_topic": false } ], "publication": { "conference_name": null, "date": "2022 May 19", "date_precision": "day", "issue": "4", "normalized_date": "2022-05-19", "pages": "789-800", "proceedings_title": null, "publisher": "", "title": "Ocular immunology and inflammation", "volume": "30", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Glutathione Trisulfide Prevents Lipopolysaccharide-induced Inflammatory Gene Expression in Retinal Pigment Epithelial Cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Medullary thymic epithelial cells (mTECs) are critical for self-tolerance induction in T cells via promiscuous expression of tissue-specific antigens (TSAs), which are controlled by the transcriptional regulator, AIRE. Whereas AIRE-expressing (Aire(+)) mTECs undergo constant turnover in the adult thymus, mechanisms underlying differentiation of postnatal mTECs remain to be discovered. Integrative analysis of single-cell assays for transposase-accessible chromatin (scATAC-seq) and single-cell RNA sequencing (scRNA-seq) suggested the presence of proliferating mTECs with a specific chromatin structure, which express high levels of Aire and co-stimulatory molecules, CD80 (Aire(+)CD80(hi)). Proliferating Aire(+)CD80(hi) mTECs detected using Fucci technology express a minimal number of Aire-dependent TSAs and are converted into quiescent Aire(+)CD80(hi) mTECs expressing high levels of TSAs after a transit amplification. These data provide evidence for the existence of transit-amplifying Aire(+)mTEC precursors during the Aire(+)mTEC differentiation process of the postnatal thymus.", "classifications": [ { "id": "Sawano", "label": "Group Sawano", "parent": "Shintaku", "type": "group" }, { "id": "Shintaku", "label": "Team Shintaku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Takahisa", "last_name": "Miyao", "name": null }, { "creator_type": "author", "first_name": "Maki", "last_name": "Miyauchi", "name": null }, { "creator_type": "author", "first_name": "S. Thomas", "last_name": "Kelly", "name": null }, { "creator_type": "author", "first_name": "Tommy W.", "last_name": "Terooatea", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Ishikawa", "name": null }, { "creator_type": "author", "first_name": "Eugene", "last_name": "Oh", "name": null }, { "creator_type": "author", "first_name": "Sotaro", "last_name": "Hirai", "name": null }, { "creator_type": "author", "first_name": "Kenta", "last_name": "Horie", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Takakura", "name": null }, { "creator_type": "author", "first_name": "Houko", "last_name": "Ohki", "name": null }, { "creator_type": "author", "first_name": "Mio", "last_name": "Hayama", "name": null }, { "creator_type": "author", "first_name": "Yuya", "last_name": "Maruyama", "name": null }, { "creator_type": "author", "first_name": "Takao", "last_name": "Seki", "name": null }, { "creator_type": "author", "first_name": "Hiroto", "last_name": "Ishii", "name": null }, { "creator_type": "author", "first_name": "Haruka", "last_name": "Yabukami", "name": null }, { "creator_type": "author", "first_name": "Masaki", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Azusa", "last_name": "Inoue", "name": null }, { "creator_type": "author", "first_name": "Asako", "last_name": "Sakaue-Sawano", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Miyawaki", "name": null }, { "creator_type": "author", "first_name": "Masafumi", "last_name": "Muratani", "name": null }, { "creator_type": "author", "first_name": "Aki", "last_name": "Minoda", "name": null }, { "creator_type": "author", "first_name": "Nobuko", "last_name": "Akiyama", "name": null }, { "creator_type": "author", "first_name": "Taishin", "last_name": "Akiyama", "name": null } ], "identifiers": { "doi": { "normalized": "10.7554/elife.73998" }, "pmcid": { "normalized": "PMC9113748" }, "pmid": { "normalized": "35578835" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Chromatin", "descriptor_ui": "D002843", "major_topic": true }, { "descriptor": "Epithelial Cells", "descriptor_ui": "D004847", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Single-Cell Analysis", "descriptor_ui": "D059010", "major_topic": true }, { "descriptor": "Thymus Gland", "descriptor_ui": "D013950", "major_topic": false }, { "descriptor": "Transposases", "descriptor_ui": "D019895", "major_topic": false } ], "publication": { "conference_name": null, "date": "2022 May 17", "date_precision": "day", "issue": "", "normalized_date": "2022-05-17", "pages": "e73998", "proceedings_title": null, "publisher": "", "title": "eLife", "volume": "11", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Integrative analysis of scRNA-seq and scATAC-seq revealed transit-amplifying thymic epithelial cells expressing autoimmune regulator.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "In embryogenesis and cancer invasion, cells collectively migrate as a cluster in 3D tissues. Many studies have elucidated mechanisms of either individual or collective cell migration on 2D substrates; however, it remains unclear how cells collectively migrate as a cluster through 3D tissues. To address this issue, we considered the interfacial tension at cell-cell boundaries expressing cortical actomyosin contractions and cell-cell adhesive interactions. The strength of this tension is polarized; i.e., spatially biased within each cell according to a chemoattractant gradient. Using a 3D vertex model, we performed numerical simulations of multicellular dynamics in 3D space. The simulations revealed that the polarized interfacial tension enables cells to migrate collectively as a cluster through a 3D tissue. In this mechanism, interfacial tension induces unidirectional flow of each cell surface from the front to the rear along the cluster surface. Importantly, this mechanism does not necessarily require convection of cells, i.e., cell rearrangement, within the cluster. Moreover, several migratory modes were induced, depending on the strengths of polarity, adhesion, and noise; i.e., cells migrate either as single cells, as a cluster, or aligned like beads on a string, as occurs in embryogenesis and cancer invasion. These results indicate that the simple expansion and contraction of cell-cell boundaries enables cells to move directionally forward and to produce the variety of collective migratory movements observed in living systems.", "classifications": [ { "id": "JPMJCR1921", "label": "JPMJCR1921", "researcher": "Itaru Imayoshi", "type": "grant" }, { "id": "Imayoshi", "label": "Group Imayoshi", "parent": "Imayoshi", "type": "group" }, { "id": "Okuda", "label": "Group Okuda", "parent": "Imayoshi", "type": "group" }, { "id": "Imayoshi", "label": "Team Imayoshi", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Satoru", "last_name": "Okuda", "name": null }, { "creator_type": "author", "first_name": "Katsuhiko", "last_name": "Sato", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.bpj.2022.04.018" }, "pmcid": { "normalized": "PMC9199099" }, "pmid": { "normalized": "35525240" } }, "mesh": [ { "descriptor": "Actomyosin", "descriptor_ui": "D000205", "major_topic": true }, { "descriptor": "Cell Communication", "descriptor_ui": "D002450", "major_topic": true }, { "descriptor": "Cell Movement", "descriptor_ui": "D002465", "major_topic": false }, { "descriptor": "Embryonic Development", "descriptor_ui": "D047108", "major_topic": false }, { "descriptor": "Surface Tension", "descriptor_ui": "D013500", "major_topic": false } ], "publication": { "conference_name": null, "date": "2022 May 17", "date_precision": "day", "issue": "10", "normalized_date": "2022-05-17", "pages": "1856-1867", "proceedings_title": null, "publisher": "", "title": "Biophysical journal", "volume": "121", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Polarized interfacial tension induces collective migration of cells, as a cluster, in a 3D tissue.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Genetic modifications, such as gene deletion and mutations, could lead to significant changes in physiological states or even cell death. Bacterial cells can adapt to diverse external stresses, such as antibiotic exposure, but can they also adapt to detrimental genetic modification? To address this issue, we visualized the response of individual Escherichia coli cells to deletion of the antibiotic resistance gene under chloramphenicol (Cp) exposure, combining the light-inducible genetic recombination and microfluidic long-term single-cell tracking. We found that a significant fraction ( approximately 40%) of resistance-gene-deleted cells demonstrated a gradual restoration of growth and stably proliferated under continuous Cp exposure without the resistance gene. Such physiological adaptation to genetic modification was not observed when the deletion was introduced in 10 hr or more advance before Cp exposure. Resistance gene deletion under Cp exposure disrupted the stoichiometric balance of ribosomal large and small subunit proteins (RplS and RpsB). However, the balance was gradually recovered in the cell lineages with restored growth. These results demonstrate that bacterial cells can adapt even to lethal genetic modifications by plastically gaining physiological resistance. However, the access to the resistance states is limited by the environmental histories and the timings of genetic modification.", "classifications": [ { "id": "JPMJCR1927", "label": "JPMJCR1927", "researcher": "Yuichi Wakamoto", "type": "grant" }, { "id": "Wakamoto", "label": "Group Wakamoto", "parent": "Wakamoto", "type": "group" }, { "id": "Wakamoto", "label": "Team Wakamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yuta", "last_name": "Koganezawa", "name": null }, { "creator_type": "author", "first_name": "Miki", "last_name": "Umetani", "name": null }, { "creator_type": "author", "first_name": "Moritoshi", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Yuichi", "last_name": "Wakamoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.7554/elife.74486" }, "pmcid": { "normalized": "PMC9090333" }, "pmid": { "normalized": "35535492" } }, "mesh": [ { "descriptor": "Adaptation, Physiological", "descriptor_ui": "D000222", "major_topic": false }, { "descriptor": "Anti-Bacterial Agents", "descriptor_ui": "D000900", "major_topic": true }, { "descriptor": "Chloramphenicol", "descriptor_ui": "D002701", "major_topic": false }, { "descriptor": "Drug Resistance, Bacterial", "descriptor_ui": "D024881", "major_topic": false }, { "descriptor": "Drug Resistance, Microbial", "descriptor_ui": "D004352", "major_topic": false }, { "descriptor": "Escherichia coli", "descriptor_ui": "D004926", "major_topic": false }, { "descriptor": "Escherichia coli Proteins", "descriptor_ui": "D029968", "major_topic": true } ], "publication": { "conference_name": null, "date": "2022 May 10", "date_precision": "day", "issue": "", "normalized_date": "2022-05-10", "pages": "e74486", "proceedings_title": null, "publisher": "", "title": "eLife", "volume": "11", "year": 2022 }, "ssbd": { "database": [ "ssbd-database-000255" ], "repository": [ "ssbd-repos-000255" ] }, "title": "History-dependent physiological adaptation to lethal genetic modification under antibiotic exposure.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Metabolic distribution of fatty acid to organelles is an essential biological process for energy homeostasis as well as for the maintenance of membrane integrity, and the metabolic pathways are strictly regulated in response to environmental stimuli. Herein, we report a fluorescent fatty acid probe, which bears an azapyrene dye that changes its absorption and emission features depending on the microenvironment polarity of the organelle into which it is transported. Owing to the environmental sensitivity of this dye, the distribution of the metabolically incorporated probe in non-polar lipid droplets, medium-polarity membranes, and the polar aqueous regions, can be visualized in different colors. Based on density scatter plots of the fluorophore, we demonstrate that the degradation of triacylglycerols in lipid droplets occurs predominantly via lipolysis rather than lipophagy in nutrition-starved hepatocytes. This tool can thus be expected to significantly advance our understanding of the lipid metabolism in living organisms.", "classifications": [ { "id": "Sato", "label": "Group Sato", "parent": "Tsuchiya", "type": "group" }, { "id": "Tsuchiya", "label": "Team Tsuchiya", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Keiji", "last_name": "Kajiwara", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Osaki", "name": null }, { "creator_type": "author", "first_name": "Steffen", "last_name": "Gressies", "name": null }, { "creator_type": "author", "first_name": "Keiko", "last_name": "Kuwata", "name": null }, { "creator_type": "author", "first_name": "Ju Hyun", "last_name": "Kim", "name": null }, { "creator_type": "author", "first_name": "Tobias", "last_name": "Gensch", "name": null }, { "creator_type": "author", "first_name": "Yoshikatsu", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Frank", "last_name": "Glorius", "name": null }, { "creator_type": "author", "first_name": "Shigehiro", "last_name": "Yamaguchi", "name": null }, { "creator_type": "author", "first_name": "Masayasu", "last_name": "Taki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41467-022-30153-6" }, "pmcid": { "normalized": "PMC9085894" }, "pmid": { "normalized": "35534485" } }, "mesh": [ { "descriptor": "Fatty Acids", "descriptor_ui": "D005227", "major_topic": true }, { "descriptor": "Fluorescent Dyes", "descriptor_ui": "D005456", "major_topic": true }, { "descriptor": "Lipid Droplets", "descriptor_ui": "D066292", "major_topic": false }, { "descriptor": "Lipid Metabolism", "descriptor_ui": "D050356", "major_topic": false }, { "descriptor": "Lipolysis", "descriptor_ui": "D008066", "major_topic": false } ], "publication": { "conference_name": null, "date": "2022 May 9", "date_precision": "day", "issue": "1", "normalized_date": "2022-05-09", "pages": "2533", "proceedings_title": null, "publisher": "", "title": "Nature communications", "volume": "13", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "A negative-solvatochromic fluorescent probe for visualizing intracellular distributions of fatty acid metabolites.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Endocardial border detection is a key step in assessing left ventricular systolic function in echocardiography. However, this process is still not sufficiently accurate, and manual retracing is often required, causing time-consuming and intra-/inter-observer variability in clinical practice. To address these clinical issues, more accurate and normalized automatic endocardial border detection would be valuable. Here, we develop a deep learning-based method for automated endocardial border detection and left ventricular functional assessment in two-dimensional echocardiographic videos. First, segmentation of the left ventricular cavity was performed in the six representative projections for a cardiac cycle. We employed four segmentation methods: U-Net, UNet++, UNet3+, and Deep Residual U-Net. UNet++ and UNet3+ showed a sufficiently high performance in the mean value of intersection over union and Dice coefficient. The accuracy of the four segmentation methods was then evaluated by calculating the mean value for the estimation error of the echocardiographic indexes. UNet++ was superior to the other segmentation methods, with the acceptable mean estimation error of the left ventricular ejection fraction of 10.8%, global longitudinal strain of 8.5%, and global circumferential strain of 5.8%, respectively. Our method using UNet++ demonstrated the best performance. This method may potentially support examiners and improve the workflow in echocardiography.", "classifications": [ { "id": "Hamamoto", "label": "Group Hamamoto", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Shunzaburo", "last_name": "Ono", "name": null }, { "creator_type": "author", "first_name": "Masaaki", "last_name": "Komatsu", "name": null }, { "creator_type": "author", "first_name": "Akira", "last_name": "Sakai", "name": null }, { "creator_type": "author", "first_name": "Hideki", "last_name": "Arima", "name": null }, { "creator_type": "author", "first_name": "Mie", "last_name": "Ochida", "name": null }, { "creator_type": "author", "first_name": "Rina", "last_name": "Aoyama", "name": null }, { "creator_type": "author", "first_name": "Suguru", "last_name": "Yasutomi", "name": null }, { "creator_type": "author", "first_name": "Ken", "last_name": "Asada", "name": null }, { "creator_type": "author", "first_name": "Syuzo", "last_name": "Kaneko", "name": null }, { "creator_type": "author", "first_name": "Tetsuo", "last_name": "Sasano", "name": null }, { "creator_type": "author", "first_name": "Ryuji", "last_name": "Hamamoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.3390/biomedicines10051082" }, "pmcid": { "normalized": "PMC9138644" }, "pmid": { "normalized": "35625819" } }, "mesh": [], "publication": { "conference_name": null, "date": "2022 May 6", "date_precision": "day", "issue": "5", "normalized_date": "2022-05-06", "pages": "1082", "proceedings_title": null, "publisher": "", "title": "Biomedicines", "volume": "10", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Automated Endocardial Border Detection and Left Ventricular Functional Assessment in Echocardiography Using Deep Learning.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Immune dysregulation plays a key role in the pathogenesis of autism. Changes occurring at the systemic level, from brain inflammation to disturbed innate/adaptive immune in the periphery, are frequently observed in patients with autism; however, the intrinsic mechanisms behind them remain elusive. We hypothesize a common etiology may lie in progenitors of different types underlying widespread immune dysregulation. By single-cell RNA sequencing (sc-RNA seq), we trace the developmental origins of immune dysregulation in a mouse model of idiopathic autism. It is found that both in aorta-gonad-mesonephros (AGM) and yolk sac (YS) progenitors, the dysregulation of HDAC1-mediated epigenetic machinery alters definitive hematopoiesis during embryogenesis and downregulates the expression of the AP-1 complex for microglia development. Subsequently, these changes result in the dysregulation of the immune system, leading to gut dysbiosis and hyperactive microglia in the brain. We further confirm that dysregulated immune profiles are associated with specific microbiota composition, which may serve as a biomarker to identify autism of immune-dysregulated subtypes. Our findings elucidate a shared mechanism for the origin of immune dysregulation from the brain to the gut in autism and provide new insight to dissecting the heterogeneity of autism, as well as the therapeutic potential of targeting immune-dysregulated autism subtypes.", "classifications": [ { "id": "Nikaido", "label": "Group Nikaido", "parent": "Fujiwara", "type": "group" }, { "id": "Fujiwara", "label": "Team Fujiwara", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Chia-Wen", "last_name": "Lin", "name": null }, { "creator_type": "author", "first_name": "Dian E.", "last_name": "Septyaningtrias", "name": null }, { "creator_type": "author", "first_name": "Hsu-Wen", "last_name": "Chao", "name": null }, { "creator_type": "author", "first_name": "Mikiko", "last_name": "Konda", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Atarashi", "name": null }, { "creator_type": "author", "first_name": "Kozue", "last_name": "Takeshita", "name": null }, { "creator_type": "author", "first_name": "Kota", "last_name": "Tamada", "name": null }, { "creator_type": "author", "first_name": "Jun", "last_name": "Nomura", "name": null }, { "creator_type": "author", "first_name": "Yohei", "last_name": "Sasagawa", "name": null }, { "creator_type": "author", "first_name": "Kaori", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Itoshi", "last_name": "Nikaido", "name": null }, { "creator_type": "author", "first_name": "Kenya", "last_name": "Honda", "name": null }, { "creator_type": "author", "first_name": "Thomas J.", "last_name": "McHugh", "name": null }, { "creator_type": "author", "first_name": "Toru", "last_name": "Takumi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41380-022-01566-y" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "35491410" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Autistic Disorder", "descriptor_ui": "D001321", "major_topic": true }, { "descriptor": "Disease Models, Animal", "descriptor_ui": "D004195", "major_topic": false }, { "descriptor": "Epigenesis, Genetic", "descriptor_ui": "D044127", "major_topic": false }, { "descriptor": "Gonads", "descriptor_ui": "D006066", "major_topic": false }, { "descriptor": "Mesonephros", "descriptor_ui": "D008650", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Yolk Sac", "descriptor_ui": "D015017", "major_topic": false } ], "publication": { "conference_name": null, "date": "2022 May 2", "date_precision": "day", "issue": "", "normalized_date": "2022-05-02", "pages": "", "proceedings_title": null, "publisher": "", "title": "Molecular psychiatry", "volume": "", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "A common epigenetic mechanism across different cellular origins underlies systemic immune dysregulation in an idiopathic autism mouse model.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Estrogen receptor (ER) positive breast cancer represents 75% of all breast cancers in women. Although patients with ER+ cancers receive endocrine therapies, more than 30% develop resistance and succumb to the disease, highlighting the need to understand endocrine resistance. Here we show an unexpected role for the cell polarity protein SCRIB as a tumor-promoter and a regulator of endocrine resistance in ER-positive breast cancer cells. SCRIB expression is induced by estrogen signaling in a MYC-dependent manner. SCRIB interacts with SLC3A2, a heteromeric component of leucine amino acid transporter SLC7A5. SLC3A2 binds to the N-terminus of SCRIB to facilitate the formation of SCRIB/SLC3A2/LLGL2/SLC7A5 quaternary complex required for membrane localization of the amino acid transporter complex. Both SCRIB and SLC3A2 are required for cell proliferation and tamoxifen resistance in ER+ cells identifying a new role for the SCRIB/SLC3A2 complex in ER+ breast cancer.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yasuhiro", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Shiori", "last_name": "Matsuda", "name": null }, { "creator_type": "author", "first_name": "Naomi", "last_name": "Ohnishi", "name": null }, { "creator_type": "author", "first_name": "Keiko", "last_name": "Endo", "name": null }, { "creator_type": "author", "first_name": "Sanae", "last_name": "Ashitani", "name": null }, { "creator_type": "author", "first_name": "Maki", "last_name": "Ohishi", "name": null }, { "creator_type": "author", "first_name": "Ayano", "last_name": "Ueno", "name": null }, { "creator_type": "author", "first_name": "Masaru", "last_name": "Tomita", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Ueda", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Senthil K.", "last_name": "Muthuswamy", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s42003-022-03363-3" }, "pmcid": { "normalized": "PMC9061724" }, "pmid": { "normalized": "35501367" } }, "mesh": [ { "descriptor": "Breast Neoplasms", "descriptor_ui": "D001943", "major_topic": true }, { "descriptor": "Cell Proliferation", "descriptor_ui": "D049109", "major_topic": false }, { "descriptor": "Cytoskeletal Proteins", "descriptor_ui": "D003598", "major_topic": false }, { "descriptor": "Drug Resistance, Neoplasm", "descriptor_ui": "D019008", "major_topic": true }, { "descriptor": "Estrogens", "descriptor_ui": "D004967", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Fusion Regulatory Protein 1, Heavy Chain", "descriptor_ui": "D027282", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Large Neutral Amino Acid-Transporter 1", "descriptor_ui": "D027283", "major_topic": false }, { "descriptor": "Membrane Proteins", "descriptor_ui": "D008565", "major_topic": true }, { "descriptor": "Receptors, Estrogen", "descriptor_ui": "D011960", "major_topic": false }, { "descriptor": "Tamoxifen", "descriptor_ui": "D013629", "major_topic": true }, { "descriptor": "Tumor Suppressor Proteins", "descriptor_ui": "D025521", "major_topic": true } ], "publication": { "conference_name": null, "date": "2022 May 2", "date_precision": "day", "issue": "1", "normalized_date": "2022-05-02", "pages": "403", "proceedings_title": null, "publisher": "", "title": "Communications biology", "volume": "5", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Polarity protein SCRIB interacts with SLC3A2 to regulate proliferation and tamoxifen resistance in ER+ breast cancer.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The topology effects of cyclization on thermal phase transition behaviors were investigated for a series of amphiphilic Pluronic copolymers of both hydrophilic-hydrophobic-hydrophilic and hydrophobic-hydrophilic-hydrophobic block sequences. The dye solubilization measurements revealed the lowered critical micelle temperatures (TCMT) along with the decreased micellization enthalpy (DeltaHmic) and entropy (DeltaSmic) for the cyclized species. Furthermore, the transmittance and dynamic light scattering (DLS) measurements indicated a block sequence-dependent effect on the clouding phenomena, where a profound decrease in cloud point (Tc) was only found for the copolymers with a hydrophilic-hydrophobic-hydrophilic block sequence. Thus, the effect of cyclization on these critical temperatures was manifested differently depending on its block sequence. Finally, a comparison of the linear hydroxy-terminated, methoxy-terminated, and cyclized species indicated the effect of cyclization to be unique from a simple elimination of the terminal hydrophilic moieties.", "classifications": [ { "id": "Yamamoto", "label": "Group Yamamoto", "parent": "Toyoshima", "type": "group" }, { "id": "Toyoshima", "label": "Team Toyoshima", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Tomohisa", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Yubo", "last_name": "Wang", "name": null }, { "creator_type": "author", "first_name": "Tomoko", "last_name": "Ono", "name": null }, { "creator_type": "author", "first_name": "Satoru", "last_name": "Chimura", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Isono", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Tajima", "name": null }, { "creator_type": "author", "first_name": "Toshifumi", "last_name": "Satoh", "name": null }, { "creator_type": "author", "first_name": "Shin-Ichiro", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Daichi", "last_name": "Ida", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Yamamoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.3390/polym14091823" }, "pmcid": { "normalized": "PMC9105568" }, "pmid": { "normalized": "35566993" } }, "mesh": [], "publication": { "conference_name": null, "date": "2022 Apr 29", "date_precision": "day", "issue": "9", "normalized_date": "2022-04-29", "pages": "1823", "proceedings_title": null, "publisher": "", "title": "Polymers", "volume": "14", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Topology and Sequence-Dependent Micellization and Phase Separation of Pluronic L35, L64, 10R5, and 17R4: Effects of Cyclization and the Chain Ends.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Spontaneous Raman microscopy, which can detect molecular vibrations in cells and tissues, could be a useful tool for the label-free assessment of non-alcoholic fatty liver disease (NAFLD). However, it is unclear whether it can be used to evaluate the nascent state of NAFLD. To address this, we analyzed the Raman spectra of rat liver tissues in the nascent state of NAFLD upon excitation at 532 nm. Raman and histochemical analyses were performed of liver tissues from rats fed a high-fat, high-cholesterol diet (HFHCD). Raman microscopic imaging analysis of formalin-fixed thin tissue slices showed hepatic steatosis, as revealed by the Raman band at 2,854 cm(-1), whereas lipid droplets were not detectable by hematoxylin-eosin staining of images until 3 days after feeding a HFHCD. Raman signals of retinol at 1,588 cm(-1) emitted from hepatic stellate cells were distributed alongside hepatic cords; the retinol content rapidly decreased after feeding a HFHCD, whereas hepatic lipid content increased inversely. Raman microscopic analysis of the surface of fresh ex vivo livers enabled early detection of lipid accumulation after a 1-day feeding a HFHCD. In conclusion, spontaneous Raman microscopy can be applied to the label-free evaluation of the nascent state of NAFLD liver tissues.", "classifications": [ { "id": "JPMJCR1925", "label": "JPMJCR1925", "researcher": "Katsumasa Fujita", "type": "grant" }, { "id": "Fujita", "label": "Group Fujita", "parent": "Fujita", "type": "group" }, { "id": "Tanaka", "label": "Group Tanaka", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Masashi", "last_name": "Takemura", "name": null }, { "creator_type": "author", "first_name": "Kentaro", "last_name": "Mochizuki", "name": null }, { "creator_type": "author", "first_name": "Yoshinori", "last_name": "Harada", "name": null }, { "creator_type": "author", "first_name": "Akira", "last_name": "Okajima", "name": null }, { "creator_type": "author", "first_name": "Michiyo", "last_name": "Hayakawa", "name": null }, { "creator_type": "author", "first_name": "Ping", "last_name": "Dai", "name": null }, { "creator_type": "author", "first_name": "Yoshito", "last_name": "Itoh", "name": null }, { "creator_type": "author", "first_name": "Hideo", "last_name": "Tanaka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1267/ahc.22-00013" }, "pmcid": { "normalized": "PMC9043435" }, "pmid": { "normalized": "35509867" } }, "mesh": [], "publication": { "conference_name": null, "date": "2022 Apr 27", "date_precision": "day", "issue": "2", "normalized_date": "2022-04-27", "pages": "57-66", "proceedings_title": null, "publisher": "", "title": "Acta histochemica et cytochemica", "volume": "55", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Label-free Assessment of the Nascent State of Rat Non-alcoholic Fatty Liver Disease Using Spontaneous Raman Microscopy.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Tissue stem cells are vital for organ homeostasis and regeneration owing to their ability to self-renew and differentiate into the various cell types that constitute organ tissue. These stem cells are formed during complex and dynamic organ development, necessitating spatial–temporal coordination of morphogenetic events and cell fate specification during this process. In recent years, technological advances have enabled the tracing of the cellular dynamics, states, and lineages of individual cells over time in relation to tissue morphological changes. These dynamic data have not only revealed the origin of tissue stem cells in various organs but have also led to an understanding of the molecular, cellular, and biophysical bases of tissue stem cell formation. Herein, we summarize recent findings on the developmental origin of tissue stem cells in the hair follicles, intestines, brain, skeletal muscles, and hematopoietic system, and further discuss how stem cell fate specification is coordinated with tissue topology.", "classifications": [ { "id": "JPMJCR1926", "label": "JPMJCR1926", "researcher": "Hironobu Fujiwara", "type": "grant" }, { "id": "Fujiwara", "label": "Group Fujiwara", "parent": "Fujiwara", "type": "group" }, { "id": "Fujiwara", "label": "Team Fujiwara", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Ritsuko", "last_name": "Morita", "name": null }, { "creator_type": "author", "first_name": "Hironobu", "last_name": "Fujiwara", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/dgd.12816" }, "pmcid": { "normalized": null }, "pmid": { "normalized": null } }, "mesh": [], "publication": { "conference_name": null, "date": "2022-04-27", "date_precision": "day", "issue": "n/a", "normalized_date": "2022-04-27", "pages": "", "proceedings_title": null, "publisher": "", "title": "Development, Growth & Differentiation", "volume": "n/a", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Tracing the developmental origin of tissue stem cells", "url": "https://onlinelibrary.wiley.com/doi/abs/10.1111/dgd.12816", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The resistance to transcription factor-mediated reprogramming into pluripotent stem cells is one of the distinctive features of cancer cells. Here we dissect the profiles of reprogramming factor binding and the subsequent transcriptional response in cancer cells to reveal its underlying mechanisms. Using clear cell sarcomas (CCSs), we show that the driver oncogene EWS/ATF1 misdirects the reprogramming factors to cancer-specific enhancers and thereby impairs the transcriptional response toward pluripotency that is otherwise provoked. Sensitization to the reprogramming cue is observed in other cancer types when the corresponding oncogenic signals are pharmacologically inhibited. Exploiting this oncogene dependence of the transcriptional \"stiffness,\" we identify mTOR signaling pathways downstream of EWS/ATF1 and discover that inhibiting mTOR activity substantially attenuates the propagation of CCS cells in vitro and in vivo. Our results demonstrate that the early transcriptional response to cell fate perturbations can be a faithful readout to identify effective therapeutics targets in cancer cells.", "classifications": [ { "id": "Yamamoto", "label": "Group Yamamoto", "parent": "Toyoshima", "type": "group" }, { "id": "Toyoshima", "label": "Team Toyoshima", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Kenji", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Kohei", "last_name": "Nagata", "name": null }, { "creator_type": "author", "first_name": "Sho", "last_name": "Ohta", "name": null }, { "creator_type": "author", "first_name": "Yutaka", "last_name": "Matsuda", "name": null }, { "creator_type": "author", "first_name": "Tomoyo", "last_name": "Ukai", "name": null }, { "creator_type": "author", "first_name": "Ichiro", "last_name": "Yasuda", "name": null }, { "creator_type": "author", "first_name": "Akira", "last_name": "Ota", "name": null }, { "creator_type": "author", "first_name": "Ryota", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Mio", "last_name": "Kabata", "name": null }, { "creator_type": "author", "first_name": "Nao", "last_name": "Sankoda", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Maeda", "name": null }, { "creator_type": "author", "first_name": "Knut", "last_name": "Woltjen", "name": null }, { "creator_type": "author", "first_name": "Liying", "last_name": "Yang", "name": null }, { "creator_type": "author", "first_name": "Reo", "last_name": "Maruyama", "name": null }, { "creator_type": "author", "first_name": "Ryohei", "last_name": "Katayama", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Yasuhiro", "last_name": "Yamada", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.celrep.2022.110721" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "35476996" } }, "mesh": [ { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Oncogenes", "descriptor_ui": "D009857", "major_topic": true }, { "descriptor": "Sarcoma, Clear Cell", "descriptor_ui": "D018227", "major_topic": true }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "TOR Serine-Threonine Kinases", "descriptor_ui": "D058570", "major_topic": false }, { "descriptor": "Transcription Factors", "descriptor_ui": "D014157", "major_topic": false } ], "publication": { "conference_name": null, "date": "2022 Apr 26", "date_precision": "day", "issue": "4", "normalized_date": "2022-04-26", "pages": "110721", "proceedings_title": null, "publisher": "", "title": "Cell reports", "volume": "39", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "The oncogene-dependent resistance to reprogramming unveils cancer therapeutic targets.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Accumulating evidence indicates that the gut microbiome and metabolites are associated with colorectal cancer (CRC). However, the influence of surgery for CRC treatment on the gut microbiome and metabolites and how it relates to CRC risk in postoperative CRC patients remain partially understood. Here, we collected 170 fecal samples from 85 CRC patients pre- and approximately 1 year postsurgery and performed shotgun metagenomic sequencing and capillary electrophoresis-time of flight mass spectrometry-based metabolomics analyses to characterize alterations between pre- and postsurgery. We determined that the relative abundance of 114 species was altered postsurgery (P < 0.005). CRC-associated species, such as Fusobacterium nucleatum, were decreased postsurgery. On the other hand, Clostridium scindens, carcinogenesis-associated deoxycholate (DCA)-producing species, and its biotransformed genes (bai operon) were increased postsurgery. The concentration of 60 fecal metabolites was also altered postsurgery (P < 0.005). Two bile acids, cholate and DCA, were increased postsurgery. We developed methods to estimate postoperative CRC risk based on the gut microbiome and metabolomic compositions using a random forest machine-learning algorithm that classifies large adenoma or early-stage CRC and healthy controls from publicly available data sets. We applied methods to preoperative samples and then compared the estimated CRC risk between the two groups according to the presence of large adenoma or tumors 5 years postsurgery (P < 0.05). Overall, our results show that the gut microbiome and metabolites dynamically change from pre- to postsurgery. In postoperative CRC patients, potential CRC risk derived from gut microbiome and metabolites still remains, which indicates the importance of follow-up assessments. IMPORTANCE The gut microbiome and metabolites are associated with CRC progression and carcinogenesis. Postoperative CRC patients are reported to be at an increased CRC risk; however, how gut microbiome and metabolites are related to CRC risk in postoperative patients remains only partially understood. In this study, we investigated the influence of surgical CRC treatment on the gut microbiome and metabolites. We found that the CRC-associated species Fusobacterium nucleatum was decreased postsurgery, whereas carcinogenesis-associated DCA and its producing species and genes were increased postsurgery. We developed methods to estimate postoperative CRC risk based on the gut microbiome and metabolomic compositions. We applied methods to compare the estimated CRC risk between two groups according to the presence of large adenoma or tumors after 5 years postsurgery. To our knowledge, this study is the first report on differences between pre- and postsurgery using metagenomics and metabolomics data analysis. Our methods might be used for CRC risk assessment in postoperative patients.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Hirotsugu", "last_name": "Shiroma", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Shiba", "name": null }, { "creator_type": "author", "first_name": "Pande Putu", "last_name": "Erawijantari", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Takamaru", "name": null }, { "creator_type": "author", "first_name": "Masayoshi", "last_name": "Yamada", "name": null }, { "creator_type": "author", "first_name": "Taku", "last_name": "Sakamoto", "name": null }, { "creator_type": "author", "first_name": "Yukihide", "last_name": "Kanemitsu", "name": null }, { "creator_type": "author", "first_name": "Sayaka", "last_name": "Mizutani", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Yutaka", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Tatsuhiro", "last_name": "Shibata", "name": null }, { "creator_type": "author", "first_name": "Shinji", "last_name": "Fukuda", "name": null }, { "creator_type": "author", "first_name": "Shinichi", "last_name": "Yachida", "name": null }, { "creator_type": "author", "first_name": "Takuji", "last_name": "Yamada", "name": null } ], "identifiers": { "doi": { "normalized": "10.1128/msystems.00018-22" }, "pmcid": { "normalized": "PMC9040882" }, "pmid": { "normalized": "35311577" } }, "mesh": [ { "descriptor": "Adenoma", "descriptor_ui": "D000236", "major_topic": true }, { "descriptor": "Carcinogenesis", "descriptor_ui": "D063646", "major_topic": false }, { "descriptor": "Colorectal Neoplasms", "descriptor_ui": "D015179", "major_topic": true }, { "descriptor": "Gastrointestinal Microbiome", "descriptor_ui": "D000069196", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Metabolome", "descriptor_ui": "D055442", "major_topic": false } ], "publication": { "conference_name": null, "date": "2022 Apr 26", "date_precision": "day", "issue": "2", "normalized_date": "2022-04-26", "pages": "e0001822", "proceedings_title": null, "publisher": "", "title": "mSystems", "volume": "7", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Surgical Treatment for Colorectal Cancer Partially Restores Gut Microbiome and Metabolome Traits.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Herein, we describe the synthesis of a toroidal Au(10) cluster stabilized by N-heterocyclic carbene and halide ligands via reduction of the corresponding NHC-Au-X complexes (X = Cl, Br, I). The significant effect of the halide ligands on the formation, stability, and further conversions of these clusters is presented. While solutions of the chloride derivatives of Au(10) show no change even upon heating, the bromide derivative readily undergoes conversion to form a biicosahedral Au(25) cluster at room temperature. For the iodide derivative, the formation of a significant amount of Au(25) was observed even upon the reduction of NHC-Au-I. The isolated bromide derivative of the Au(25) cluster displays a relatively high (ca. 15%) photoluminescence quantum yield, attributed to the high rigidity of the cluster, which is enforced by multiple CH-pi interactions within the molecular structure. Density functional theory computations are used to characterize the electronic structure and optical absorption of the Au(10) cluster. (13)C-Labeling is employed to assist with characterization of the products and to observe their conversions by NMR spectroscopy.", "classifications": [ { "id": "Nanbo", "label": "Group Nanbo", "parent": "Tsuchiya", "type": "group" }, { "id": "Tsuchiya", "label": "Team Tsuchiya", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Paul A.", "last_name": "Lummis", "name": null }, { "creator_type": "author", "first_name": "Kimberly M.", "last_name": "Osten", "name": null }, { "creator_type": "author", "first_name": "Tetyana I.", "last_name": "Levchenko", "name": null }, { "creator_type": "author", "first_name": "Maryam", "last_name": "Sabooni Asre Hazer", "name": null }, { "creator_type": "author", "first_name": "Sami", "last_name": "Malola", "name": null }, { "creator_type": "author", "first_name": "Bryan", "last_name": "Owens-Baird", "name": null }, { "creator_type": "author", "first_name": "Alex J.", "last_name": "Veinot", "name": null }, { "creator_type": "author", "first_name": "Emily L.", "last_name": "Albright", "name": null }, { "creator_type": "author", "first_name": "Gabriele", "last_name": "Schatte", "name": null }, { "creator_type": "author", "first_name": "Shinjiro", "last_name": "Takano", "name": null }, { "creator_type": "author", "first_name": "Kirill", "last_name": "Kovnir", "name": null }, { "creator_type": "author", "first_name": "Kevin G.", "last_name": "Stamplecoskie", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Tsukuda", "name": null }, { "creator_type": "author", "first_name": "Hannu", "last_name": "Hakkinen", "name": null }, { "creator_type": "author", "first_name": "Masakazu", "last_name": "Nambo", "name": null }, { "creator_type": "author", "first_name": "Cathleen M.", "last_name": "Crudden", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/jacsau.2c00004" }, "pmcid": { "normalized": "PMC9088291" }, "pmid": { "normalized": "35557749" } }, "mesh": [], "publication": { "conference_name": null, "date": "2022 Apr 25", "date_precision": "day", "issue": "4", "normalized_date": "2022-04-25", "pages": "875-885", "proceedings_title": null, "publisher": "", "title": "JACS Au", "volume": "2", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "NHC-Stabilized Au(10) Nanoclusters and Their Conversion to Au(25) Nanoclusters.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Subtilase cytotoxin (SubAB) is an AB5 toxin mainly produced by the locus of enterocyte effacement-negative Shiga-toxigenic Escherichia coli (STEC) strain such as O113:H21, yet the contribution of SubAB to STEC infectious disease is unclear. We found that SubAB reduced activation of the STEC O113:H21 infection-induced non-canonical NLRP3 inflammasome and interleukin (IL)-1beta and IL-18 production in murine macrophages. Downstream of lipopolysaccharide signaling, SubAB suppressed caspase-11 expression by inhibiting interferon-beta/STAT1 signaling, followed by disrupting formation of the NLRP3/caspase-1 assembly. These inhibitions were regulated by PERK/IRE1alpha-dependent endoplasmic reticulum (ER) stress signaling initiated by cleavage of the host ER chaperone BiP by SubAB. Our murine model of SubAB-producing Citrobacter rodentium demonstrated that SubAB promoted C. rodentium proliferation and worsened symptoms such as intestinal hyperplasia and diarrhea. These findings highlight the inhibitory effect of SubAB on the NLRP3 inflammasome via ER stress, which may be associated with STEC survival and infectious disease pathogenicity in hosts.", "classifications": [ { "id": "JPMJCR2024", "label": "JPMJCR2024", "researcher": "Motohiro Nishida", "type": "grant" }, { "id": "Akaike", "label": "Group Akaike", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Group Nishida", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Hiroyasu", "last_name": "Tsutsuki", "name": null }, { "creator_type": "author", "first_name": "Tianli", "last_name": "Zhang", "name": null }, { "creator_type": "author", "first_name": "Kinnosuke", "last_name": "Yahiro", "name": null }, { "creator_type": "author", "first_name": "Katsuhiko", "last_name": "Ono", "name": null }, { "creator_type": "author", "first_name": "Yukio", "last_name": "Fujiwara", "name": null }, { "creator_type": "author", "first_name": "Sunao", "last_name": "Iyoda", "name": null }, { "creator_type": "author", "first_name": "Fan-Yan", "last_name": "Wei", "name": null }, { "creator_type": "author", "first_name": "Kazuaki", "last_name": "Monde", "name": null }, { "creator_type": "author", "first_name": "Kazuko", "last_name": "Seto", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Ohnishi", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Oshiumi", "name": null }, { "creator_type": "author", "first_name": "Takaaki", "last_name": "Akaike", "name": null }, { "creator_type": "author", "first_name": "Tomohiro", "last_name": "Sawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.isci.2022.104050" }, "pmcid": { "normalized": "PMC8957020" }, "pmid": { "normalized": "35345462" } }, "mesh": [], "publication": { "conference_name": null, "date": "2022 Apr 15", "date_precision": "day", "issue": "4", "normalized_date": "2022-04-15", "pages": "104050", "proceedings_title": null, "publisher": "", "title": "iScience", "volume": "25", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Subtilase cytotoxin from Shiga-toxigenic Escherichia coli impairs the inflammasome and exacerbates enteropathogenic bacterial infection.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The in vitro generation of germ cells from pluripotent stem cells (PSCs) can have a substantial effect on future reproductive medicine and animal breeding. A decade ago, in vitro gametogenesis was established in the mouse. However, induction of primordial germ cell-like cells (PGCLCs) to produce gametes has not been achieved in any other species. Here, we demonstrate the induction of functional PGCLCs from rat PSCs. We show that epiblast-like cells in floating aggregates form rat PGCLCs. The gonadal somatic cells support maturation and epigenetic reprogramming of the PGCLCs. When rat PGCLCs are transplanted into the seminiferous tubules of germline-less rats, functional spermatids-that is, those capable of siring viable offspring-are generated. Insights from our rat model will elucidate conserved and divergent mechanisms essential for the broad applicability of in vitro gametogenesis.", "classifications": [ { "id": "Yamamoto", "label": "Group Yamamoto", "parent": "Toyoshima", "type": "group" }, { "id": "Toyoshima", "label": "Team Toyoshima", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Mami", "last_name": "Oikawa", "name": null }, { "creator_type": "author", "first_name": "Hisato", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Sanbo", "name": null }, { "creator_type": "author", "first_name": "Naoaki", "last_name": "Mizuno", "name": null }, { "creator_type": "author", "first_name": "Kenyu", "last_name": "Iwatsuki", "name": null }, { "creator_type": "author", "first_name": "Tomoya", "last_name": "Takashima", "name": null }, { "creator_type": "author", "first_name": "Keiko", "last_name": "Yamauchi", "name": null }, { "creator_type": "author", "first_name": "Fumika", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Shinohara", "name": null }, { "creator_type": "author", "first_name": "Hiromitsu", "last_name": "Nakauchi", "name": null }, { "creator_type": "author", "first_name": "Kazuki", "last_name": "Kurimoto", "name": null }, { "creator_type": "author", "first_name": "Masumi", "last_name": "Hirabayashi", "name": null }, { "creator_type": "author", "first_name": "Toshihiro", "last_name": "Kobayashi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1126/science.abl4412" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "35389778" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": true }, { "descriptor": "Epigenomics", "descriptor_ui": "D057890", "major_topic": false }, { "descriptor": "Gametogenesis", "descriptor_ui": "D005718", "major_topic": true }, { "descriptor": "Germ Cells", "descriptor_ui": "D005854", "major_topic": false }, { "descriptor": "Germ Layers", "descriptor_ui": "D005855", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Pluripotent Stem Cells", "descriptor_ui": "D039904", "major_topic": true }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false } ], "publication": { "conference_name": null, "date": "2022 Apr 8", "date_precision": "day", "issue": "6589", "normalized_date": "2022-04-08", "pages": "176-179", "proceedings_title": null, "publisher": "", "title": "Science (New York, N.Y.)", "volume": "376", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Functional primordial germ cell-like cells from pluripotent stem cells in rats.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The pancreatic islet vasculature is of fundamental importance to the beta-cell response to obesity-associated insulin resistance. To explore islet vascular alterations in the pathogenesis of type 2 diabetes, we evaluated two insulin resistance models: ob/ob mice, which sustain large beta-cell mass and hyperinsulinemia, and db/db mice, which progress to diabetes due to secondary beta-cell compensation failure for insulin secretion. Time-dependent changes in islet vasculature and blood flow were investigated using tomato lectin staining and in vivo live imaging. Marked islet capillary dilation was observed in ob/ob mice, but this adaptive change was blunted in db/db mice. Islet blood flow volume was augmented in ob/ob mice, whereas it was reduced in db/db mice. The protein concentrations of total and phosphorylated endothelial nitric oxide synthase (eNOS) at Ser1177 were increased in ob/ob islets, while they were diminished in db/db mice, indicating decreased eNOS activity. This was accompanied by an increased retention of advanced glycation end-products in db/db blood vessels. Amelioration of diabetes by Elovl6 deficiency involved a restoration of capillary dilation, blood flow, and eNOS phosphorylation in db/db islets. Our findings suggest that the disability of islet capillary dilation due to endothelial dysfunction impairs local islet blood flow, which may play a role in the loss of beta-cell function and further exacerbate type 2 diabetes.", "classifications": [ { "id": "Miyamoto", "label": "Group Miyamoto", "parent": "Wakamoto", "type": "group" }, { "id": "Wakamoto", "label": "Team Wakamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yuka", "last_name": "Okajima", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Matsuzaka", "name": null }, { "creator_type": "author", "first_name": "Shun", "last_name": "Miyazaki", "name": null }, { "creator_type": "author", "first_name": "Kaori", "last_name": "Motomura", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Ohno", "name": null }, { "creator_type": "author", "first_name": "Rahul", "last_name": "Sharma", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Shimura", "name": null }, { "creator_type": "author", "first_name": "Nurani", "last_name": "Istiqamah", "name": null }, { "creator_type": "author", "first_name": "Song-Iee", "last_name": "Han", "name": null }, { "creator_type": "author", "first_name": "Yuhei", "last_name": "Mizunoe", "name": null }, { "creator_type": "author", "first_name": "Yoshinori", "last_name": "Osaki", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Iwasaki", "name": null }, { "creator_type": "author", "first_name": "Shigeru", "last_name": "Yatoh", "name": null }, { "creator_type": "author", "first_name": "Hiroaki", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Hirohito", "last_name": "Sone", "name": null }, { "creator_type": "author", "first_name": "Takafumi", "last_name": "Miyamoto", "name": null }, { "creator_type": "author", "first_name": "Yuichi", "last_name": "Aita", "name": null }, { "creator_type": "author", "first_name": "Yoshinori", "last_name": "Takeuchi", "name": null }, { "creator_type": "author", "first_name": "Motohiro", "last_name": "Sekiya", "name": null }, { "creator_type": "author", "first_name": "Naoya", "last_name": "Yahagi", "name": null }, { "creator_type": "author", "first_name": "Yoshimi", "last_name": "Nakagawa", "name": null }, { "creator_type": "author", "first_name": "Tsutomu", "last_name": "Tomita", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Shimano", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.bbadis.2022.166339" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "35017029" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Blood Flow Velocity", "descriptor_ui": "D001783", "major_topic": false }, { "descriptor": "Blood Vessels", "descriptor_ui": "D001808", "major_topic": false }, { "descriptor": "Diabetes Mellitus, Type 2", "descriptor_ui": "D003924", "major_topic": false }, { "descriptor": "Disease Models, Animal", "descriptor_ui": "D004195", "major_topic": false }, { "descriptor": "Fatty Acid Elongases", "descriptor_ui": "D000081031", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Glycation End Products, Advanced", "descriptor_ui": "D017127", "major_topic": false }, { "descriptor": "Insulin", "descriptor_ui": "D007328", "major_topic": false }, { "descriptor": "Insulin Resistance", "descriptor_ui": "D007333", "major_topic": false }, { "descriptor": "Islets of Langerhans", "descriptor_ui": "D007515", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Mice, Obese", "descriptor_ui": "D008820", "major_topic": false }, { "descriptor": "Nitric Oxide Synthase Type III", "descriptor_ui": "D052250", "major_topic": false }, { "descriptor": "Phosphorylation", "descriptor_ui": "D010766", "major_topic": false } ], "publication": { "conference_name": null, "date": "2022 Apr 1", "date_precision": "day", "issue": "4", "normalized_date": "2022-04-01", "pages": "166339", "proceedings_title": null, "publisher": "", "title": "Biochimica et biophysica acta. Molecular basis of disease", "volume": "1868", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Morphological and functional adaptation of pancreatic islet blood vessels to insulin resistance is impaired in diabetic db/db mice.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "PURPOSE: Post-cataract surgery bacterial endophthalmitis is a serious postoperative complication, and Enterococcus spp.-induced endophthalmitis reportedly has a particularly poor visual prognosis. This study aimed to demonstrate the prophylactic effect of postoperative intracameral phage administration in Enterococcus faecalis-induced endophthalmitis after cataract surgery in rabbits. METHODS: Endophthalmitis was induced in rabbits by injecting E. faecalis into the anterior chamber just after lensectomy while simultaneously administering either phage phiEF24C-P2 or vehicle. Retinal function was evaluated using electroretinography. The number of viable bacteria and myeloperoxidase (MPO) activity in the eye and histopathologic examinations were analyzed 48 hours after infection. RESULTS: In the vehicle-treated group, retinal function at 24 hours after infection was impaired, and the number of viable bacteria and MPO activity in the eye increased 48 hours later. In the phage-administered group, retinal function was maintained; the number of viable bacteria and MPO activity were significantly suppressed. Histopathologic examinations showed disruption of the retinal layers and the presence of numerous E. faecalis in the lens capsule and vitreous cavity in vehicle-treated eyes. In contrast, retinal structures were intact, and no E. faecalis staining was observed in phage-treated eyes. No retinal dysfunction was observed in the group that received phage only without lensectomy; almost no phage was detected in the eyes after 14 days of treatment. CONCLUSIONS: Phage administration in the anterior chamber did not cause retinal dysfunction and suppressed postoperative endophthalmitis in rabbits. TRANSLATIONAL RELEVANCE: In vivo results of intracameral phage administration suggest that phages are a promising prophylactic candidate for postoperative endophthalmitis.", "classifications": [ { "id": "Suzuki", "label": "Group Suzuki", "parent": "Takekawa", "type": "group" }, { "id": "Takekawa", "label": "Team Takekawa", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Tatsuma", "last_name": "Kishimoto", "name": null }, { "creator_type": "author", "first_name": "Waka", "last_name": "Ishida", "name": null }, { "creator_type": "author", "first_name": "Isana", "last_name": "Nakajima", "name": null }, { "creator_type": "author", "first_name": "Takako", "last_name": "Ujihara", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Jumpei", "last_name": "Uchiyama", "name": null }, { "creator_type": "author", "first_name": "Shigenobu", "last_name": "Matsuzaki", "name": null }, { "creator_type": "author", "first_name": "Ken", "last_name": "Fukuda", "name": null } ], "identifiers": { "doi": { "normalized": "10.1167/tvst.11.4.2" }, "pmcid": { "normalized": "PMC8976926" }, "pmid": { "normalized": "35363260" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Bacteriophages", "descriptor_ui": "D001435", "major_topic": true }, { "descriptor": "Cataract", "descriptor_ui": "D002386", "major_topic": true }, { "descriptor": "Endophthalmitis", "descriptor_ui": "D009877", "major_topic": true }, { "descriptor": "Enterococcus faecalis", "descriptor_ui": "D013293", "major_topic": false }, { "descriptor": "Eye Infections, Bacterial", "descriptor_ui": "D015818", "major_topic": true }, { "descriptor": "Rabbits", "descriptor_ui": "D011817", "major_topic": false } ], "publication": { "conference_name": null, "date": "2022 Apr 1", "date_precision": "day", "issue": "4", "normalized_date": "2022-04-01", "pages": "2", "proceedings_title": null, "publisher": "", "title": "Translational vision science & technology", "volume": "11", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Intracameral Bacteriophage Injection as Postoperative Prophylaxis for Enterococcus faecalis-Induced Endophthalmitis After Cataract Surgery in Rabbits.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Cells change their metabolism in response to internal and external conditions by regulating the trans-omic network, which is a global biochemical network with multiple omic layers. Metabolic flux is a direct measure of the activity of a metabolic reaction that provides valuable information for understanding complex trans-omic networks. Over the past decades, techniques to determine metabolic fluxes, including 13C-metabolic flux analysis (13C-MFA), flux balance analysis (FBA), and kinetic modeling, have been developed. Recent studies that acquire quantitative metabolic flux and multi-omic data have greatly advanced the quantitative understanding and prediction of metabolism-centric trans-omic networks. In this review, we present an overview of 13C-MFA, FBA, and kinetic modeling as the main techniques to determine quantitative metabolic fluxes, and discuss their advantages and disadvantages. We also introduce case studies with the aim of understanding complex metabolism-centric trans-omic networks based on the determination of metabolic fluxes.", "classifications": [ { "id": "JPMJCR2123", "label": "JPMJCR2123", "researcher": "Shinya Kuroda", "type": "grant" }, { "id": "Kuroda", "label": "Group Kuroda", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Satoshi", "last_name": "Ohno", "name": null }, { "creator_type": "author", "first_name": "Saori", "last_name": "Uematsu", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Kuroda", "name": null } ], "identifiers": { "doi": { "normalized": "10.1042/bcj20210596" }, "pmcid": { "normalized": "PMC9022981" }, "pmid": { "normalized": "35356967" } }, "mesh": [ { "descriptor": "Kinetics", "descriptor_ui": "D007700", "major_topic": false }, { "descriptor": "Metabolic Flux Analysis", "descriptor_ui": "D064688", "major_topic": true }, { "descriptor": "Metabolic Networks and Pathways", "descriptor_ui": "D053858", "major_topic": true } ], "publication": { "conference_name": null, "date": "2022 Mar 31", "date_precision": "day", "issue": "6", "normalized_date": "2022-03-31", "pages": "787-804", "proceedings_title": null, "publisher": "", "title": "The Biochemical journal", "volume": "479", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Quantitative metabolic fluxes regulated by trans-omic networks.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Naked mole-rats (NMRs) have a very low spontaneous carcinogenesis rate, which has prompted studies on the responsible mechanisms to provide clues for human cancer prevention. However, it remains unknown whether and how NMR tissues respond to experimental carcinogenesis induction. Here, we show that NMRs exhibit extraordinary resistance against potent chemical carcinogenesis induction through a dampened inflammatory response. Although carcinogenic insults damaged skin cells of both NMRs and mice, NMR skin showed markedly lower immune cell infiltration. NMRs harbour loss-of-function mutations in RIPK3 and MLKL genes, which are essential for necroptosis, a type of necrotic cell death that activates strong inflammation. In mice, disruption of Ripk3 reduced immune cell infiltration and delayed carcinogenesis. Therefore, necroptosis deficiency may serve as a cancer resistance mechanism via attenuating the inflammatory response in NMRs. Our study sheds light on the importance of a dampened inflammatory response as a non-cell-autonomous cancer resistance mechanism in NMRs.", "classifications": [ { "id": "Yamamoto", "label": "Group Yamamoto", "parent": "Toyoshima", "type": "group" }, { "id": "Toyoshima", "label": "Team Toyoshima", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Kaori", "last_name": "Oka", "name": null }, { "creator_type": "author", "first_name": "Shusuke", "last_name": "Fujioka", "name": null }, { "creator_type": "author", "first_name": "Yoshimi", "last_name": "Kawamura", "name": null }, { "creator_type": "author", "first_name": "Yoshihiro", "last_name": "Komohara", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Chujo", "name": null }, { "creator_type": "author", "first_name": "Koki", "last_name": "Sekiguchi", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Yamamura", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Oiwa", "name": null }, { "creator_type": "author", "first_name": "Natsuko", "last_name": "Omamiuda-Ishikawa", "name": null }, { "creator_type": "author", "first_name": "Shohei", "last_name": "Komaki", "name": null }, { "creator_type": "author", "first_name": "Yoichi", "last_name": "Sutoh", "name": null }, { "creator_type": "author", "first_name": "Satoko", "last_name": "Sakurai", "name": null }, { "creator_type": "author", "first_name": "Kazuhito", "last_name": "Tomizawa", "name": null }, { "creator_type": "author", "first_name": "Hidemasa", "last_name": "Bono", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Shimizu", "name": null }, { "creator_type": "author", "first_name": "Kimi", "last_name": "Araki", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Yasuhiro", "last_name": "Yamada", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Oshiumi", "name": null }, { "creator_type": "author", "first_name": "Kyoko", "last_name": "Miura", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s42003-022-03241-y" }, "pmcid": { "normalized": "PMC8967925" }, "pmid": { "normalized": "35354912" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Carcinogenesis", "descriptor_ui": "D063646", "major_topic": false }, { "descriptor": "Inflammation", "descriptor_ui": "D007249", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mole Rats", "descriptor_ui": "D019577", "major_topic": true }, { "descriptor": "Necroptosis", "descriptor_ui": "D000079302", "major_topic": true }, { "descriptor": "Skin", "descriptor_ui": "D012867", "major_topic": false } ], "publication": { "conference_name": null, "date": "2022 Mar 30", "date_precision": "day", "issue": "1", "normalized_date": "2022-03-30", "pages": "287", "proceedings_title": null, "publisher": "", "title": "Communications biology", "volume": "5", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Resistance to chemical carcinogenesis induction via a dampened inflammatory response in naked mole-rats.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Biologically derived metal-organic frameworks (Bio-MOFs) are significant, as they can be used in cutting-edge biomedical applications such as targeted gene delivery. Herein, adenine (Ade) and unnatural amino acids coordinate with Zn(2+) to produce biocompatible frameworks, KBM-1 and KBM-2, with extremely defined porous channels. They feature an accessible Watson-Crick Ade face that is available for further hydrogen bonding and can load single-stranded DNA (ssDNA) with 13 and 41% efficiency for KBM-1 and KBM-2, respectively. Treatment of these frameworks with thymine (Thy), as a competitive guest for base pairing with the Ade open sites, led to more than 50% reduction of ssDNA loading. Moreover, KBM-2 loaded Thy-rich ssDNA more efficiently than Thy-free ssDNA. These findings support the role of the Thy-Ade base pairing in promoting ssDNA loading. Furthermore, theoretical calculations using the self-consistent charge density functional tight-binding (SCC-DFTB) method verified the role of hydrogen bonding and van der Waals type interactions in this host-guest interface. KBM-1 and KBM-2 can protect ssDNA from enzymatic degradation and release it at acidic pH. Most importantly, these biocompatible frameworks can efficiently deliver genetic cargo with retained activity to the cell nucleus. We envisage that this class of Bio-MOFs can find immediate applicability as biomimics for sensing, stabilizing, and delivering genetic materials.", "classifications": [ { "id": "Hijikata", "label": "Group Hijikata", "parent": "Tsuchiya", "type": "group" }, { "id": "Tsuchiya", "label": "Team Tsuchiya", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Santanu", "last_name": "Chand", "name": null }, { "creator_type": "author", "first_name": "Othman", "last_name": "Alahmed", "name": null }, { "creator_type": "author", "first_name": "Walaa S.", "last_name": "Baslyman", "name": null }, { "creator_type": "author", "first_name": "Avishek", "last_name": "Dey", "name": null }, { "creator_type": "author", "first_name": "Somayah", "last_name": "Qutub", "name": null }, { "creator_type": "author", "first_name": "Ranajit", "last_name": "Saha", "name": null }, { "creator_type": "author", "first_name": "Yuh", "last_name": "Hijikata", "name": null }, { "creator_type": "author", "first_name": "Manal", "last_name": "Alaamery", "name": null }, { "creator_type": "author", "first_name": "Niveen M.", "last_name": "Khashab", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/jacsau.1c00516" }, "pmcid": { "normalized": "PMC8969998" }, "pmid": { "normalized": "35373199" } }, "mesh": [], "publication": { "conference_name": null, "date": "2022 Mar 28", "date_precision": "day", "issue": "3", "normalized_date": "2022-03-28", "pages": "623-630", "proceedings_title": null, "publisher": "", "title": "JACS Au", "volume": "2", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "DNA-Mimicking Metal-Organic Frameworks with Accessible Adenine Faces for Complementary Base Pairing.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Uncovering the mechanisms that establish naive pluripotency in humans is crucial for the future applications of pluripotent stem cells including the production of human blastoids. However, the regulatory pathways that control the establishment of naive pluripotency by reprogramming are largely unknown. Here, we use genome-wide screening to identify essential regulators as well as major impediments of human primed to naive pluripotent stem cell reprogramming. We discover that factors essential for cell state change do not typically undergo changes at the level of gene expression but rather are repurposed with new functions. Mechanistically, we establish that the variant Polycomb complex PRC1.3 and PRDM14 jointly repress developmental and gene regulatory factors to ensure naive cell reprogramming. In addition, small-molecule inhibitors of reprogramming impediments improve naive cell reprogramming beyond current methods. Collectively, this work defines the principles controlling the establishment of human naive pluripotency and also provides new insights into mechanisms that destabilize and reconfigure cell identity during cell state transitions.", "classifications": [ { "id": "Yusa", "label": "Group Yusa", "parent": "Eiraku", "type": "group" }, { "id": "Eiraku", "label": "Team Eiraku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Amanda J.", "last_name": "Collier", "name": null }, { "creator_type": "author", "first_name": "Adam", "last_name": "Bendall", "name": null }, { "creator_type": "author", "first_name": "Charlene", "last_name": "Fabian", "name": null }, { "creator_type": "author", "first_name": "Andrew A.", "last_name": "Malcolm", "name": null }, { "creator_type": "author", "first_name": "Katarzyna", "last_name": "Tilgner", "name": null }, { "creator_type": "author", "first_name": "Claudia I.", "last_name": "Semprich", "name": null }, { "creator_type": "author", "first_name": "Katarzyna", "last_name": "Wojdyla", "name": null }, { "creator_type": "author", "first_name": "Paola Serena", "last_name": "Nisi", "name": null }, { "creator_type": "author", "first_name": "Kamal", "last_name": "Kishore", "name": null }, { "creator_type": "author", "first_name": "Valar Nila", "last_name": "Roamio Franklin", "name": null }, { "creator_type": "author", "first_name": "Bahar", "last_name": "Mirshekar-Syahkal", "name": null }, { "creator_type": "author", "first_name": "Clive", "last_name": "D'Santos", "name": null }, { "creator_type": "author", "first_name": "Kathrin", "last_name": "Plath", "name": null }, { "creator_type": "author", "first_name": "Kosuke", "last_name": "Yusa", "name": null }, { "creator_type": "author", "first_name": "Peter J.", "last_name": "Rugg-Gunn", "name": null } ], "identifiers": { "doi": { "normalized": "10.1126/sciadv.abk0013" }, "pmcid": { "normalized": "PMC8956265" }, "pmid": { "normalized": "35333572" } }, "mesh": [ { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Cellular Reprogramming", "descriptor_ui": "D065150", "major_topic": true }, { "descriptor": "Gene Expression Regulation", "descriptor_ui": "D005786", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Pluripotent Stem Cells", "descriptor_ui": "D039904", "major_topic": true }, { "descriptor": "Polycomb Repressive Complex 1", "descriptor_ui": "D063150", "major_topic": true } ], "publication": { "conference_name": null, "date": "2022 Mar 25", "date_precision": "day", "issue": "12", "normalized_date": "2022-03-25", "pages": "eabk0013", "proceedings_title": null, "publisher": "", "title": "Science advances", "volume": "8", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Genome-wide screening identifies Polycomb repressive complex 1.3 as an essential regulator of human naive pluripotent cell reprogramming.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The development of the plant body starts with spore germination in bryophytes. In many cases, the first division of the spore occurs after germination and cell elongation of the spore. In Marchantia polymorpha, asymmetric division occurs upon spore germination to generate two daughter cells: the larger one retains the ability to divide and develops into the thallus via sporeling or protonema, while the smaller one maintains tip growth and differentiates into the first rhizoid, providing a scaffold for initial development. Although spore germination of M. polymorpha was described in the 19th century, the intracellular processes of the first asymmetric division of the spore have not been well characterized. In this study, we used live-cell imaging analyses to elucidate microtubule dynamics during the first asymmetric division concomitantly with germination. In particular, we demonstrated that the preprophase band was not formed in the spore and that the bipolar prospindle, which is a microtubule structure surrounding the nucleus during prophase, migrated from the center to the periphery in the spore, suggesting that it was the earliest visible sign of cell polarity. We also showed that the occurrence of asymmetric division depended on actin filaments. Our findings regarding the first division of the spore in M. polymorpha will lead to a better model for cell-autonomous asymmetric division in plants.", "classifications": [ { "id": "Higaki", "label": "Group Higaki", "parent": "Ueda", "type": "group" }, { "id": "Ueda", "label": "Team Ueda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yuuki", "last_name": "Sakai", "name": null }, { "creator_type": "author", "first_name": "Takumi", "last_name": "Higaki", "name": null }, { "creator_type": "author", "first_name": "Kimitsune", "last_name": "Ishizaki", "name": null }, { "creator_type": "author", "first_name": "Ryuichi", "last_name": "Nishihama", "name": null }, { "creator_type": "author", "first_name": "Takayuki", "last_name": "Kohchi", "name": null }, { "creator_type": "author", "first_name": "Seiichiro", "last_name": "Hasezawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.5511/plantbiotechnology.21.1217b" }, "pmcid": { "normalized": "PMC9200083" }, "pmid": { "normalized": "35800969" } }, "mesh": [], "publication": { "conference_name": null, "date": "2022 Mar 25", "date_precision": "day", "issue": "1", "normalized_date": "2022-03-25", "pages": "5-12", "proceedings_title": null, "publisher": "", "title": "Plant biotechnology (Tokyo, Japan)", "volume": "39", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Migration of prospindle before the first asymmetric division in germinating spore of Marchantia polymorpha.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The recent discovery of calix[3]pyrrole, a porphyrinogen-like tripyrrolic macrocycle, has provided an unprecedented strain-induced ring expansion reaction into calix[6]pyrrole. Here, we synthesized calix[n]furan[3-n]pyrrole (n=1 approximately 3) macrocycles to investigate the reaction scope and mechanism of the ring expansion. Single crystal X-ray analysis and theoretical calculations revealed that macrocyclic ring strain increases as the number of inner NH sites increases. While calix[1]furan[2]pyrrole exhibited almost quantitative conversion into calix[2]furan[4]pyrrole within 5 minutes, less-strained calix[2]furan[1]pyrrole and calix[3]furan were inert. However, N-methylation of calix[2]furan[1]pyrrole induced a ring-expansion reaction that enabled the isolation of a linear reaction intermediate. The mechanism analysis revealed that the ring expansion consists of regioselective ring cleavage and subsequent cyclodimerization. This reaction was further utilized for synthesis of calix[6]-type macrocycles.", "classifications": [ { "id": "Hijikata", "label": "Group Hijikata", "parent": "Tsuchiya", "type": "group" }, { "id": "Tsuchiya", "label": "Team Tsuchiya", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yuya", "last_name": "Inaba", "name": null }, { "creator_type": "author", "first_name": "Yu", "last_name": "Kakibayashi", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Ide", "name": null }, { "creator_type": "author", "first_name": "Jenny", "last_name": "Pirillo", "name": null }, { "creator_type": "author", "first_name": "Yuh", "last_name": "Hijikata", "name": null }, { "creator_type": "author", "first_name": "Tomoki", "last_name": "Yoneda", "name": null }, { "creator_type": "author", "first_name": "Yasuhide", "last_name": "Inokuma", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/chem.202200056" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "35137995" } }, "mesh": [ { "descriptor": "Calixarenes", "descriptor_ui": "D047250", "major_topic": true }, { "descriptor": "Pyrroles", "descriptor_ui": "D011758", "major_topic": true } ], "publication": { "conference_name": null, "date": "2022 Mar 22", "date_precision": "day", "issue": "17", "normalized_date": "2022-03-22", "pages": "e202200056", "proceedings_title": null, "publisher": "", "title": "Chemistry (Weinheim an der Bergstrasse, Germany)", "volume": "28", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Strain-Induced Ring Expansion Reactions of Calix[3]pyrrole-Related Macrocycles.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Symptom overlap between meibomian gland dysfunction (MGD) and dry eye (DE) makes it difficult to distinguish between these two conditions on the basis of symptoms alone. We searched for characteristic symptoms that might help to distinguish MGD from DE on the basis of a population-based study. Subjects comprised 311 residents of Takushima island (18 to 96 years), including 117 individuals with MGD and 114 with DE. Responses to a symptom-related questionnaire (19 items) were subjected to factor analysis, and univariate regression analysis was performed to identify ocular surface parameters associated with characteristic symptoms of MGD. Factor analysis revealed aggregation of symptoms according to three factors: Factor 1 related to Symptom Score, Factor 2 to DE, and Factor 3 to MGD. Symptoms associated with DE included 11 items, whereas the only item related to MGD was tearing sensation. Pearson's correlation analysis revealed that tearing sensation was associated with tear meniscus height (TMH), noninvasive tear-film breakup time, fluorescein staining score, meiboscore, meibum grade, and Schirmer value. Subjects with MGD experienced significantly more tearing and had a larger TMH than did those without MGD (p = 0.0334). Tearing sensation may thus be a characteristic symptom of MGD. Physicians should suspect MGD who complain of tearing sensation.", "classifications": [ { "id": "Suzuki", "label": "Group Suzuki", "parent": "Takekawa", "type": "group" }, { "id": "Takekawa", "label": "Team Takekawa", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Reiko", "last_name": "Arita", "name": null }, { "creator_type": "author", "first_name": "Takanori", "last_name": "Mizoguchi", "name": null }, { "creator_type": "author", "first_name": "Motoko", "last_name": "Kawashima", "name": null }, { "creator_type": "author", "first_name": "Shima", "last_name": "Fukuoka", "name": null }, { "creator_type": "author", "first_name": "Shizuka", "last_name": "Koh", "name": null }, { "creator_type": "author", "first_name": "Rika", "last_name": "Shirakawa", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Naoyuki", "last_name": "Morishige", "name": null } ], "identifiers": { "doi": { "normalized": "10.3390/jcm11061715" }, "pmcid": { "normalized": "PMC8952797" }, "pmid": { "normalized": "35330039" } }, "mesh": [], "publication": { "conference_name": null, "date": "2022 Mar 19", "date_precision": "day", "issue": "6", "normalized_date": "2022-03-19", "pages": "1715", "proceedings_title": null, "publisher": "", "title": "Journal of clinical medicine", "volume": "11", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Exploratory Search for Characteristic Symptoms to Distinguish Meibomian Gland Dysfunction from Dry Eye in a Population-Based Study in Japan.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Trees are thought to have acquired a mechanically optimized shape through evolution, but a scientific methodology to investigate the mechanical rationality of tree morphology remains to be established. The aim of this study was to develop a new method for 3D reconstruction of actual tree shape and to establish a theoretical formulation for elucidating the structure and function of tree branches. We obtained 3D point cloud data of tree shape of Japanese zelkova (Zelkova serrata) and Japanese larch (Larix kaempferi) using the NavVis Lidar scanner, then applied a cylinder structure extraction from point cloud data with error estimation. We then formulated the mechanical stress of branches under gravity using the elastic theory, and performed finite element method simulations to evaluate the mechanical characteristics. Subsequently, we constructed a mechanics-based theoretical formulation of branch development that ensures constant bending stress produces various branching patterns depending on growth properties. The derived theory recapitulates the trade-off among branch growth anisotropy, stress-gravity length, and branch shape, which may open the quantitative way to evaluate mechanical and morphological rationality of tree branches.", "classifications": [ { "id": "Tsugawa", "label": "Group Tsugawa", "parent": "Ueda", "type": "group" }, { "id": "Ueda", "label": "Team Ueda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Satoru", "last_name": "Tsugawa", "name": null }, { "creator_type": "author", "first_name": "Kaname", "last_name": "Teratsuji", "name": null }, { "creator_type": "author", "first_name": "Fumio", "last_name": "Okura", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Noshita", "name": null }, { "creator_type": "author", "first_name": "Masaki", "last_name": "Tateno", "name": null }, { "creator_type": "author", "first_name": "Jingyao", "last_name": "Zhang", "name": null }, { "creator_type": "author", "first_name": "Taku", "last_name": "Demura", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41598-022-08030-5" }, "pmcid": { "normalized": "PMC8904476" }, "pmid": { "normalized": "35260741" } }, "mesh": [ { "descriptor": "Finite Element Analysis", "descriptor_ui": "D020342", "major_topic": false }, { "descriptor": "Gravitation", "descriptor_ui": "D006112", "major_topic": false }, { "descriptor": "Larix", "descriptor_ui": "D028221", "major_topic": true }, { "descriptor": "Stress, Mechanical", "descriptor_ui": "D013314", "major_topic": false }, { "descriptor": "Trees", "descriptor_ui": "D014197", "major_topic": true } ], "publication": { "conference_name": null, "date": "2022 Mar 8", "date_precision": "day", "issue": "1", "normalized_date": "2022-03-08", "pages": "4054", "proceedings_title": null, "publisher": "", "title": "Scientific reports", "volume": "12", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Exploring the mechanical and morphological rationality of tree branch structure based on 3D point cloud analysis and the finite element method.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Although the number of patients with heart failure is increasing, a sufficient treatment agent has not been established. Oxidative stress and inflammation play important roles in the development of myocardial remodeling. When thioredoxin (Trx), an endogenous anti-oxidative and inflammatory modulator with a molecular weight of 12 kDa, is exogenously administered, it disappears rapidly from the blood circulation. In this study, we prepared a long-acting Trx, by fusing human Trx (HSA-Trx) with human serum albumin (HSA) and evaluated its efficacy in treating drug-induced heart failure. Drug-induced cardiomyopathy was created by intraperitoneally administering doxorubicin (Dox) to mice three times per week. A decrease in heart weight, increased myocardial fibrosis and markers for myocardial damage that were observed in the Dox group were suppressed by HSA-Trx administration. HSA-Trx also suppressed the expression of atrogin-1 and myostatin, myocardial atrophy factors in addition to suppressing oxidative stress and inflammation. In the Dox group, a decreased expression of endogenous Trx in cardiac tissue and an increased expression of macrophage migration inhibitory factor were observed, but these changes were restored to normal levels by HSA-Trx administration. These findings suggest that HSA-Trx improves the pathological condition associated with Dox-induced cardiomyopathy by its anti-oxidative/anti-inflammatory and myocardial atrophy inhibitory action.", "classifications": [ { "id": "Nishida", "label": "Group Nishida", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Ryota", "last_name": "Murata", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Hiroto", "last_name": "Nosaki", "name": null }, { "creator_type": "author", "first_name": "Kento", "last_name": "Nishida", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Maeda", "name": null }, { "creator_type": "author", "first_name": "Motohiro", "last_name": "Nishida", "name": null }, { "creator_type": "author", "first_name": "Toru", "last_name": "Maruyama", "name": null } ], "identifiers": { "doi": { "normalized": "10.3390/pharmaceutics14030562" }, "pmcid": { "normalized": "PMC8953310" }, "pmid": { "normalized": "35335938" } }, "mesh": [], "publication": { "conference_name": null, "date": "2022 Mar 3", "date_precision": "day", "issue": "3", "normalized_date": "2022-03-03", "pages": "562", "proceedings_title": null, "publisher": "", "title": "Pharmaceutics", "volume": "14", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Long-Acting Thioredoxin Ameliorates Doxorubicin-Induced Cardiomyopathy via Its Anti-Oxidative and Anti-Inflammatory Action.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "We previously demonstrated different expression patterns of the neuronal nitric oxide synthase (nNOS) splicing variants, nNOS-mu and nNOS-alpha, in the rat brain; however, their exact functions have not been fully elucidated. In this study, we compared the enzymatic activities of nNOS-mu and nNOS-alpha and investigated intracellular redox signaling in nNOS-expressing PC12 cells, stimulated with a neurotoxicant, 1-methyl-4-phenylpyridinium ion (MPP(+)), to enhance the nNOS uncoupling reaction. Using in vitro studies, we show that nNOS-mu produced nitric oxide (NO), as did nNOS-alpha, in the presence of tetrahydrobiopterin (BH4), an important cofactor for the enzymatic activity. However, nNOS-mu generated more NO and less superoxide than nNOS-alpha in the absence of BH4. MPP (+) treatment induced more reactive oxygen species (ROS) production in nNOS-alpha-expressing PC12 cells than in those expressing nNOS-mu, which correlated with the intracellular production of 8-nitroguanosine 3',5'-cyclic monophosphate (8-nitro-cGMP), a downstream messenger of nNOS redox signaling, and apoptosis in these cells. Furthermore, post-treatment with 8-nitro-cGMP aggravated MPP(+)-induced cytotoxicity via activation of the H-Ras/extracellular signal-regulated kinase signaling pathway. In conclusion, our results provide strong evidence that nNOS-mu exhibits distinctive enzymatic properties of NO/ROS production, contributing to the regulation of intracellular redox signaling, including the downstream production of 8-nitro-cGMP.", "classifications": [ { "id": "Akaike", "label": "Group Akaike", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Shingo", "last_name": "Kasamatsu", "name": null }, { "creator_type": "author", "first_name": "Hiroyasu", "last_name": "Tsutsuki", "name": null }, { "creator_type": "author", "first_name": "Tomoaki", "last_name": "Ida", "name": null }, { "creator_type": "author", "first_name": "Tomohiro", "last_name": "Sawa", "name": null }, { "creator_type": "author", "first_name": "Yasuo", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Takaaki", "last_name": "Akaike", "name": null }, { "creator_type": "author", "first_name": "Hideshi", "last_name": "Ihara", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.niox.2022.01.004" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "35033681" } }, "mesh": [ { "descriptor": "1-Methyl-4-phenylpyridinium", "descriptor_ui": "D015655", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Apoptosis", "descriptor_ui": "D017209", "major_topic": false }, { "descriptor": "Cyclic GMP", "descriptor_ui": "D006152", "major_topic": false }, { "descriptor": "Mitogen-Activated Protein Kinase 1", "descriptor_ui": "D019950", "major_topic": false }, { "descriptor": "Mitogen-Activated Protein Kinase 3", "descriptor_ui": "D048052", "major_topic": false }, { "descriptor": "Nitric Oxide", "descriptor_ui": "D009569", "major_topic": false }, { "descriptor": "Nitric Oxide Synthase Type I", "descriptor_ui": "D052248", "major_topic": false }, { "descriptor": "Oxidation-Reduction", "descriptor_ui": "D010084", "major_topic": false }, { "descriptor": "PC12 Cells", "descriptor_ui": "D016716", "major_topic": false }, { "descriptor": "Phosphorylation", "descriptor_ui": "D010766", "major_topic": false }, { "descriptor": "Protein Isoforms", "descriptor_ui": "D020033", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Superoxides", "descriptor_ui": "D013481", "major_topic": false } ], "publication": { "conference_name": null, "date": "2022 Mar 1", "date_precision": "day", "issue": "", "normalized_date": "2022-03-01", "pages": "44-52", "proceedings_title": null, "publisher": "", "title": "Nitric oxide : biology and chemistry", "volume": "120", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Regulation of nitric oxide/reactive oxygen species redox signaling by nNOS splicing variants.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Longitudinal bone growth is achieved by a tightly controlled process termed endochondral bone formation. C-type natriuretic peptide (CNP) stimulates endochondral bone formation through binding to its specific receptor, guanylyl cyclase (GC)-B. However, CNP/GC-B signaling dynamics in different stages of endochondral bone formation have not been fully clarified, especially in terms of the interaction between the cyclic guanine monophosphate (cGMP) and cyclic adenosine monophosphate (cAMP) pathways. Here, we demonstrated that CNP activates the cAMP/protein kinase A (PKA) pathway and that this activation contributed to the elongation of the hypertrophic zone in the growth plate. Cells of the chondrogenic line ATDC5 were transfected with Forster resonance energy transfer (FRET)-based cGMP and PKA biosensors. Dual-FRET imaging revealed that CNP increased intracellular cGMP levels and PKA activities in chondrocytes. Further, CNP-induced PKA activation was enhanced following differentiation of ATDC5 cells. Live imaging of the fetal growth plate of transgenic mice, expressing a FRET biosensor for PKA, PKAchu mice, showed that CNP predominantly activates the PKA in the hypertrophic chondrocytes. Additionally, histological analysis of the growth plate of PKAchu mice demonstrated that CNP increased the length of the growth plate, but coadministration of a PKA inhibitor, H89, inhibited the growth-promoting effect of CNP only in the hypertrophic zone. In summary, we revealed that CNP-induced cGMP elevation activated the cAMP/PKA pathway, and clarified that this PKA activation contributed to the bone growth-promoting effect of CNP in hypertrophic chondrocytes. These results provide insights regarding the cross-talk between cGMP and cAMP signaling in endochondral bone formation and in the physiological role of the CNP/GC-B system.", "classifications": [], "creators": [ { "creator_type": "author", "first_name": "Keisho", "last_name": "Hirota", "name": null }, { "creator_type": "author", "first_name": "Tsuyoshi", "last_name": "Hirashima", "name": null }, { "creator_type": "author", "first_name": "Kazuki", "last_name": "Horikawa", "name": null }, { "creator_type": "author", "first_name": "Akihiro", "last_name": "Yasoda", "name": null }, { "creator_type": "author", "first_name": "Michiyuki", "last_name": "Matsuda", "name": null } ], "identifiers": { "doi": { "normalized": "10.1210/endocr/bqac005" }, "pmcid": { "normalized": "PMC8826897" }, "pmid": { "normalized": "35041746" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "Chondrocytes", "descriptor_ui": "D019902", "major_topic": false }, { "descriptor": "Cyclic AMP", "descriptor_ui": "D000242", "major_topic": false }, { "descriptor": "Cyclic AMP-Dependent Protein Kinases", "descriptor_ui": "D017868", "major_topic": false }, { "descriptor": "Cyclic GMP", "descriptor_ui": "D006152", "major_topic": false }, { "descriptor": "Enzyme Activation", "descriptor_ui": "D004789", "major_topic": false }, { "descriptor": "Fluorescence Resonance Energy Transfer", "descriptor_ui": "D031541", "major_topic": false }, { "descriptor": "Growth Plate", "descriptor_ui": "D006132", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Transgenic", "descriptor_ui": "D008822", "major_topic": false }, { "descriptor": "Natriuretic Peptide, C-Type", "descriptor_ui": "D020098", "major_topic": false }, { "descriptor": "Osteogenesis", "descriptor_ui": "D010012", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false } ], "publication": { "conference_name": null, "date": "2022 Mar 1", "date_precision": "day", "issue": "3", "normalized_date": "2022-03-01", "pages": "bqac005", "proceedings_title": null, "publisher": "", "title": "Endocrinology", "volume": "163", "year": 2022 }, "ssbd": { "database": [], "repository": [ "ssbd-repos-000221" ] }, "title": "C-type Natriuretic Peptide-induced PKA Activation Promotes Endochondral Bone Formation in Hypertrophic Chondrocytes.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Cyclic oligoketones composed of 3,3-dimethylpentane-2,4-diones showed crown ether-like alkali metal ion binding behavior with association constants up to 1.7 x 10(4) M(-1) in chloroform/acetonitrile (v/v, 9/1). The binding properties have been used for catalysis in the Finkelstein reaction in a low-polarity solvent. Furthermore, novel ion-binding hosts were generated by terminal functionalization of linear polyketones.", "classifications": [ { "id": "Hijikata", "label": "Group Hijikata", "parent": "Tsuchiya", "type": "group" }, { "id": "Tsuchiya", "label": "Team Tsuchiya", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Narito", "last_name": "Ozawa", "name": null }, { "creator_type": "author", "first_name": "Kilingaru I.", "last_name": "Shivakumar", "name": null }, { "creator_type": "author", "first_name": "Muthuchamy", "last_name": "Murugavel", "name": null }, { "creator_type": "author", "first_name": "Yuya", "last_name": "Inaba", "name": null }, { "creator_type": "author", "first_name": "Tomoki", "last_name": "Yoneda", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Ide", "name": null }, { "creator_type": "author", "first_name": "Jenny", "last_name": "Pirillo", "name": null }, { "creator_type": "author", "first_name": "Yuh", "last_name": "Hijikata", "name": null }, { "creator_type": "author", "first_name": "Yasuhide", "last_name": "Inokuma", "name": null } ], "identifiers": { "doi": { "normalized": "10.1039/d2cc00361a" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "35170625" } }, "mesh": [], "publication": { "conference_name": null, "date": "2022 Mar 1", "date_precision": "day", "issue": "18", "normalized_date": "2022-03-01", "pages": "2971-2974", "proceedings_title": null, "publisher": "", "title": "Chemical communications (Cambridge, England)", "volume": "58", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Alkali metal ion binding using cyclic polyketones.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Diagnostic support tools based on artificial intelligence (AI) have exhibited high performance in various medical fields. However, their clinical application remains challenging because of the lack of explanatory power in AI decisions (black box problem), making it difficult to build trust with medical professionals. Nevertheless, visualizing the internal representation of deep neural networks will increase explanatory power and improve the confidence of medical professionals in AI decisions. We propose a novel deep learning-based explainable representation \"graph chart diagram\" to support fetal cardiac ultrasound screening, which has low detection rates of congenital heart diseases due to the difficulty in mastering the technique. Screening performance improves using this representation from 0.966 to 0.975 for experts, 0.829 to 0.890 for fellows, and 0.616 to 0.748 for residents in the arithmetic mean of area under the curve of a receiver operating characteristic curve. This is the first demonstration wherein examiners used deep learning-based explainable representation to improve the performance of fetal cardiac ultrasound screening, highlighting the potential of explainable AI to augment examiner capabilities.", "classifications": [ { "id": "Hamamoto", "label": "Group Hamamoto", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Akira", "last_name": "Sakai", "name": null }, { "creator_type": "author", "first_name": "Masaaki", "last_name": "Komatsu", "name": null }, { "creator_type": "author", "first_name": "Reina", "last_name": "Komatsu", "name": null }, { "creator_type": "author", "first_name": "Ryu", "last_name": "Matsuoka", "name": null }, { "creator_type": "author", "first_name": "Suguru", "last_name": "Yasutomi", "name": null }, { "creator_type": "author", "first_name": "Ai", "last_name": "Dozen", "name": null }, { "creator_type": "author", "first_name": "Kanto", "last_name": "Shozu", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Arakaki", "name": null }, { "creator_type": "author", "first_name": "Hidenori", "last_name": "Machino", "name": null }, { "creator_type": "author", "first_name": "Ken", "last_name": "Asada", "name": null }, { "creator_type": "author", "first_name": "Syuzo", "last_name": "Kaneko", "name": null }, { "creator_type": "author", "first_name": "Akihiko", "last_name": "Sekizawa", "name": null }, { "creator_type": "author", "first_name": "Ryuji", "last_name": "Hamamoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.3390/biomedicines10030551" }, "pmcid": { "normalized": "PMC8945208" }, "pmid": { "normalized": "35327353" } }, "mesh": [], "publication": { "conference_name": null, "date": "2022 Feb 25", "date_precision": "day", "issue": "3", "normalized_date": "2022-02-25", "pages": "551", "proceedings_title": null, "publisher": "", "title": "Biomedicines", "volume": "10", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Medical Professional Enhancement Using Explainable Artificial Intelligence in Fetal Cardiac Ultrasound Screening.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The spread of cancer to bone is invariably fatal, with complex cross-talk between tumor cells and the bone microenvironment responsible for driving disease progression. By combining in silico analysis of patient datasets with metabolomic profiling of prostate cancer cells cultured with bone cells, we demonstrate the changing energy requirements of prostate cancer cells in the bone microenvironment, identifying the pentose phosphate pathway (PPP) as elevated in prostate cancer bone metastasis, with increased expression of the PPP rate-limiting enzyme glucose-6-phosphate dehydrogenase (G6PD) associated with a reduction in progression-free survival. Genetic and pharmacologic manipulation demonstrates that G6PD inhibition reduces prostate cancer growth and migration, associated with changes in cellular redox state and increased chemosensitivity. Genetic blockade of G6PD in vivo results in reduction of tumor growth within bone. In summary, we demonstrate the metabolic plasticity of prostate cancer cells in the bone microenvironment, identifying the PPP and G6PD as metabolic targets for the treatment of prostate cancer bone metastasis.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Jessica", "last_name": "Whitburn", "name": null }, { "creator_type": "author", "first_name": "Srinivasa R.", "last_name": "Rao", "name": null }, { "creator_type": "author", "first_name": "Emma V.", "last_name": "Morris", "name": null }, { "creator_type": "author", "first_name": "Sho", "last_name": "Tabata", "name": null }, { "creator_type": "author", "first_name": "Akiyoshi", "last_name": "Hirayama", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "James R.", "last_name": "Edwards", "name": null }, { "creator_type": "author", "first_name": "Zeynep", "last_name": "Kaya", "name": null }, { "creator_type": "author", "first_name": "Charlotte", "last_name": "Palmer", "name": null }, { "creator_type": "author", "first_name": "Freddie C.", "last_name": "Hamdy", "name": null }, { "creator_type": "author", "first_name": "Claire M.", "last_name": "Edwards", "name": null } ], "identifiers": { "doi": { "normalized": "10.1126/sciadv.abf9096" }, "pmcid": { "normalized": "PMC8880772" }, "pmid": { "normalized": "35213227" } }, "mesh": [ { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Glucosephosphate Dehydrogenase", "descriptor_ui": "D005954", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Metabolomics", "descriptor_ui": "D055432", "major_topic": false }, { "descriptor": "Pentose Phosphate Pathway", "descriptor_ui": "D010427", "major_topic": false }, { "descriptor": "Prostatic Neoplasms", "descriptor_ui": "D011471", "major_topic": true }, { "descriptor": "Tumor Microenvironment", "descriptor_ui": "D059016", "major_topic": false } ], "publication": { "conference_name": null, "date": "2022 Feb 25", "date_precision": "day", "issue": "8", "normalized_date": "2022-02-25", "pages": "eabf9096", "proceedings_title": null, "publisher": "", "title": "Science advances", "volume": "8", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Metabolic profiling of prostate cancer in skeletal microenvironments identifies G6PD as a key mediator of growth and survival.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Arabidopsis thaliana has 13 genes belonging to the myosin XI family. Myosin XI-2 (MYA2) plays a major role in the generation of cytoplasmic streaming in Arabidopsis cells. In this study, we investigated the molecular properties of MYA2 expressed by the baculovirus transfer system. Actin-activated ATPase activity and in vitro motility assays revealed that activity of MYA2 was regulated by the globular tail domain (GTD). When the GTD is not bound to the cargo, the GTD inhibits ADP dissociation from the motor domain. Optical nanometry of single MYA2 molecules, combining total internal reflection fluorescence microscopy (TIRFM) and the fluorescence imaging with one-nanometer accuracy (FIONA) method, revealed that the MYA2 processively moved on actin with three different step sizes: - 28 nm, 29 nm, and 60 nm, at low ATP concentrations. This result indicates that MYA2 uses two different stepping modes; hand-over-hand and inchworm-like. Force measurement using optical trapping showed the stall force of MYA2 was 0.85 pN, which was less than half that of myosin V (2-3 pN). These results indicated that MYA2 has different transport properties from that of the myosin V responsible for vesicle transport in animal cells. Such properties may enable multiple myosin XIs to transport organelles quickly and smoothly, for the generation of cytoplasmic streaming in plant cells.", "classifications": [ { "id": "Iwaki", "label": "Group Iwaki", "parent": "Toyoshima", "type": "group" }, { "id": "Toyoshima", "label": "Team Toyoshima", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Takeshi", "last_name": "Haraguchi", "name": null }, { "creator_type": "author", "first_name": "Kohji", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Takamitsu", "last_name": "Morikawa", "name": null }, { "creator_type": "author", "first_name": "Kohei", "last_name": "Yoshimura", "name": null }, { "creator_type": "author", "first_name": "Nao", "last_name": "Shoji", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Kimura", "name": null }, { "creator_type": "author", "first_name": "Mitsuhiro", "last_name": "Iwaki", "name": null }, { "creator_type": "author", "first_name": "Motoki", "last_name": "Tominaga", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41598-022-07047-0" }, "pmcid": { "normalized": "PMC8873201" }, "pmid": { "normalized": "35210477" } }, "mesh": [ { "descriptor": "Arabidopsis", "descriptor_ui": "D017360", "major_topic": false }, { "descriptor": "Cytoplasmic Streaming", "descriptor_ui": "D003595", "major_topic": true }, { "descriptor": "Myosin Heavy Chains", "descriptor_ui": "D018995", "major_topic": false }, { "descriptor": "Organelles", "descriptor_ui": "D015388", "major_topic": false } ], "publication": { "conference_name": null, "date": "2022 Feb 24", "date_precision": "day", "issue": "1", "normalized_date": "2022-02-24", "pages": "3150", "proceedings_title": null, "publisher": "", "title": "Scientific reports", "volume": "12", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Autoregulation and dual stepping mode of MYA2, an Arabidopsis myosin XI responsible for cytoplasmic streaming.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Glucose homeostasis is maintained by modulation of metabolic flux. Enzymes and metabolites regulate the involved metabolic pathways. Dysregulation of glucose homeostasis is a pathological event in obesity. Analyzing metabolic pathways and the mechanisms contributing to obesity-associated dysregulation in vivo is challenging. Here, we introduce OMELET: Omics-Based Metabolic Flux Estimation without Labeling for Extended Trans-omic Analysis. OMELET uses metabolomic, proteomic, and transcriptomic data to identify relative changes in metabolic flux, and to calculate contributions of metabolites, enzymes, and transcripts to the changes in metabolic flux. By evaluating the livers of fasting ob/ob mice, we found that increased metabolic flux through gluconeogenesis resulted primarily from increased transcripts, whereas that through the pyruvate cycle resulted from both increased transcripts and changes in substrates of metabolic enzymes. With OMELET, we identified mechanisms underlying the obesity-associated dysregulation of metabolic flux in the liver.", "classifications": [ { "id": "JPMJCR2123", "label": "JPMJCR2123", "researcher": "Shinya Kuroda", "type": "grant" }, { "id": "Kuroda", "label": "Group Kuroda", "parent": "Kuroda", "type": "group" }, { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Saori", "last_name": "Uematsu", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Ohno", "name": null }, { "creator_type": "author", "first_name": "Kaori Y.", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Hatano", "name": null }, { "creator_type": "author", "first_name": "Toshiya", "last_name": "Kokaji", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Kubota", "name": null }, { "creator_type": "author", "first_name": "Ken-Ichi", "last_name": "Hironaka", "name": null }, { "creator_type": "author", "first_name": "Yutaka", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Masaki", "last_name": "Matsumoto", "name": null }, { "creator_type": "author", "first_name": "Keiichi I.", "last_name": "Nakayama", "name": null }, { "creator_type": "author", "first_name": "Akiyoshi", "last_name": "Hirayama", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Kuroda", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.isci.2022.103787" }, "pmcid": { "normalized": "PMC8859528" }, "pmid": { "normalized": "35243212" } }, "mesh": [], "publication": { "conference_name": null, "date": "2022 Feb 18", "date_precision": "day", "issue": "2", "normalized_date": "2022-02-18", "pages": "103787", "proceedings_title": null, "publisher": "", "title": "iScience", "volume": "25", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Multi-omics-based label-free metabolic flux inference reveals obesity-associated dysregulatory mechanisms in liver glucose metabolism.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The asymmetric oxidation of a sulfur-containing nine-membered heterocycle was achieved for the late-stage introduction of chirality to the substituents of pi-electron systems. The oxidation of the sulfur atom considerably influenced the phase-transition behaviour and crystallinity of the resulting pi-electron systems.", "classifications": [ { "id": "Hijikata", "label": "Group Hijikata", "parent": "Tsuchiya", "type": "group" }, { "id": "Tsuchiya", "label": "Team Tsuchiya", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Masahiro", "last_name": "Hayakawa", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Horike", "name": null }, { "creator_type": "author", "first_name": "Yuh", "last_name": "Hijikata", "name": null }, { "creator_type": "author", "first_name": "Kosuke", "last_name": "Yasui", "name": null }, { "creator_type": "author", "first_name": "Shigehiro", "last_name": "Yamaguchi", "name": null }, { "creator_type": "author", "first_name": "Aiko", "last_name": "Fukazawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1039/d1cc06996a" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "35103262" } }, "mesh": [], "publication": { "conference_name": null, "date": "2022 Feb 17", "date_precision": "day", "issue": "15", "normalized_date": "2022-02-17", "pages": "2548-2551", "proceedings_title": null, "publisher": "", "title": "Chemical communications (Cambridge, England)", "volume": "58", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Late-stage modification of pi-electron systems based on asymmetric oxidation of a medium-sized sulfur-containing ring.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Cancer-specific cell surface antigens are ideal therapeutic targets for monoclonal antibody (mAb)-based therapy. Here, we report that multiple myeloma (MM), an incurable hematological malignancy, can be specifically targeted by an mAb that recognizes a ubiquitously present protein, CD98 heavy chain (hc) (also known as SLC3A2). We screened more than 10,000 mAb clones raised against MM cells and identified R8H283, an mAb that bound MM cells but not normal hematopoietic or nonhematopoietic cells. R8H283 specifically recognized CD98hc. R8H283 did not react with monomers of CD98hc; instead, it bound CD98hc in heterodimers with a CD98 light chain (CD98lc), a complex that functions as an amino acid transporter. CD98 heterodimers were abundant on MM cells and took up amino acids for constitutive production of immunoglobulin. Although CD98 heterodimers were also present on normal leukocytes, R8H283 did not react with them. The glycoforms of CD98hc present on normal leukocytes were distinct from those present on MM cells, which may explain the lack of R8H283 reactivity to normal leukocytes. R8H283 exerted anti-MM effects without damaging normal hematopoietic cells. These findings suggested that R8H283 is a candidate for mAb-based therapies for MM. In addition, our findings showed that a cancer-specific conformational epitope in a ubiquitous protein, which cannot be identified by transcriptome or proteome analyses, can be found by extensive screening of primary human tumor samples.", "classifications": [ { "id": "Yusa", "label": "Group Yusa", "parent": "Eiraku", "type": "group" }, { "id": "Eiraku", "label": "Team Eiraku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Kana", "last_name": "Hasegawa", "name": null }, { "creator_type": "author", "first_name": "Shunya", "last_name": "Ikeda", "name": null }, { "creator_type": "author", "first_name": "Moto", "last_name": "Yaga", "name": null }, { "creator_type": "author", "first_name": "Kouki", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Rika", "last_name": "Urakawa", "name": null }, { "creator_type": "author", "first_name": "Akie", "last_name": "Iehara", "name": null }, { "creator_type": "author", "first_name": "Mai", "last_name": "Iwai", "name": null }, { "creator_type": "author", "first_name": "Seishin", "last_name": "Hashiguchi", "name": null }, { "creator_type": "author", "first_name": "Soyoko", "last_name": "Morimoto", "name": null }, { "creator_type": "author", "first_name": "Fumihiro", "last_name": "Fujiki", "name": null }, { "creator_type": "author", "first_name": "Hiroko", "last_name": "Nakajima", "name": null }, { "creator_type": "author", "first_name": "Jun", "last_name": "Nakata", "name": null }, { "creator_type": "author", "first_name": "Sumiyuki", "last_name": "Nishida", "name": null }, { "creator_type": "author", "first_name": "Akihiro", "last_name": "Tsuboi", "name": null }, { "creator_type": "author", "first_name": "Yoshihiro", "last_name": "Oka", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Yoshihara", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Manabe", "name": null }, { "creator_type": "author", "first_name": "Hiroyoshi", "last_name": "Ichihara", "name": null }, { "creator_type": "author", "first_name": "Atsuko", "last_name": "Mugitani", "name": null }, { "creator_type": "author", "first_name": "Yasutaka", "last_name": "Aoyama", "name": null }, { "creator_type": "author", "first_name": "Takafumi", "last_name": "Nakao", "name": null }, { "creator_type": "author", "first_name": "Asao", "last_name": "Hirose", "name": null }, { "creator_type": "author", "first_name": "Masayuki", "last_name": "Hino", "name": null }, { "creator_type": "author", "first_name": "Shiho", "last_name": "Ueda", "name": null }, { "creator_type": "author", "first_name": "Katsuto", "last_name": "Takenaka", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Masuko", "name": null }, { "creator_type": "author", "first_name": "Koichi", "last_name": "Akashi", "name": null }, { "creator_type": "author", "first_name": "Takahiro", "last_name": "Maruno", "name": null }, { "creator_type": "author", "first_name": "Susumu", "last_name": "Uchiyama", "name": null }, { "creator_type": "author", "first_name": "Shinji", "last_name": "Takamatsu", "name": null }, { "creator_type": "author", "first_name": "Naoki", "last_name": "Wada", "name": null }, { "creator_type": "author", "first_name": "Eiichi", "last_name": "Morii", "name": null }, { "creator_type": "author", "first_name": "Shushi", "last_name": "Nagamori", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Motooka", "name": null }, { "creator_type": "author", "first_name": "Yoshikatsu", "last_name": "Kanai", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Oji", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Nakagawa", "name": null }, { "creator_type": "author", "first_name": "Noriyuki", "last_name": "Kijima", "name": null }, { "creator_type": "author", "first_name": "Haruhiko", "last_name": "Kishima", "name": null }, { "creator_type": "author", "first_name": "Atsuyo", "last_name": "Ikeda", "name": null }, { "creator_type": "author", "first_name": "Takayuki", "last_name": "Ogino", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Shintani", "name": null }, { "creator_type": "author", "first_name": "Tateki", "last_name": "Kubo", "name": null }, { "creator_type": "author", "first_name": "Emiko", "last_name": "Mihara", "name": null }, { "creator_type": "author", "first_name": "Kosuke", "last_name": "Yusa", "name": null }, { "creator_type": "author", "first_name": "Haruo", "last_name": "Sugiyama", "name": null }, { "creator_type": "author", "first_name": "Junichi", "last_name": "Takagi", "name": null }, { "creator_type": "author", "first_name": "Eiji", "last_name": "Miyoshi", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Kumanogoh", "name": null }, { "creator_type": "author", "first_name": "Naoki", "last_name": "Hosen", "name": null } ], "identifiers": { "doi": { "normalized": "10.1126/scitranslmed.aax7706" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "35171652" } }, "mesh": [ { "descriptor": "Antibodies, Monoclonal", "descriptor_ui": "D000911", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Multiple Myeloma", "descriptor_ui": "D009101", "major_topic": true } ], "publication": { "conference_name": null, "date": "2022 Feb 16", "date_precision": "day", "issue": "632", "normalized_date": "2022-02-16", "pages": "eaax7706", "proceedings_title": null, "publisher": "", "title": "Science translational medicine", "volume": "14", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Selective targeting of multiple myeloma cells with a monoclonal antibody recognizing the ubiquitous protein CD98 heavy chain.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The balance of programmed death-1 (PD-1)-expressing CD8(+) T cells and regulatory T (Treg) cells in the tumor microenvironment (TME) determines the clinical efficacy of PD-1 blockade therapy through the competition of their reactivation. However, factors that determine this balance remain unknown. Here, we show that Treg cells gain higher PD-1 expression than effector T cells in highly glycolytic tumors, including MYC-amplified tumors and liver tumors. Under low-glucose environments via glucose consumption by tumor cells, Treg cells actively absorbed lactic acid (LA) through monocarboxylate transporter 1 (MCT1), promoting NFAT1 translocation into the nucleus, thereby enhancing the expression of PD-1, whereas PD-1 expression by effector T cells was dampened. PD-1 blockade invigorated the PD-1-expressing Treg cells, resulting in treatment failure. We propose that LA in the highly glycolytic TME is an active checkpoint for the function of Treg cells in the TME via upregulation of PD-1 expression.", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Shogo", "last_name": "Kumagai", "name": null }, { "creator_type": "author", "first_name": "Shohei", "last_name": "Koyama", "name": null }, { "creator_type": "author", "first_name": "Kota", "last_name": "Itahashi", "name": null }, { "creator_type": "author", "first_name": "Tokiyoshi", "last_name": "Tanegashima", "name": null }, { "creator_type": "author", "first_name": "Yi-Tzu", "last_name": "Lin", "name": null }, { "creator_type": "author", "first_name": "Yosuke", "last_name": "Togashi", "name": null }, { "creator_type": "author", "first_name": "Takahiro", "last_name": "Kamada", "name": null }, { "creator_type": "author", "first_name": "Takuma", "last_name": "Irie", "name": null }, { "creator_type": "author", "first_name": "Genki", "last_name": "Okumura", "name": null }, { "creator_type": "author", "first_name": "Hidetoshi", "last_name": "Kono", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Rika", "last_name": "Fujii", "name": null }, { "creator_type": "author", "first_name": "Sho", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Atsuo", "last_name": "Sai", "name": null }, { "creator_type": "author", "first_name": "Shota", "last_name": "Fukuoka", "name": null }, { "creator_type": "author", "first_name": "Eri", "last_name": "Sugiyama", "name": null }, { "creator_type": "author", "first_name": "Go", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Owari", "name": null }, { "creator_type": "author", "first_name": "Hitomi", "last_name": "Nishinakamura", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Sugiyama", "name": null }, { "creator_type": "author", "first_name": "Yuka", "last_name": "Maeda", "name": null }, { "creator_type": "author", "first_name": "Akihito", "last_name": "Kawazoe", "name": null }, { "creator_type": "author", "first_name": "Hiroki", "last_name": "Yukami", "name": null }, { "creator_type": "author", "first_name": "Keigo", "last_name": "Chida", "name": null }, { "creator_type": "author", "first_name": "Yuuki", "last_name": "Ohara", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Shinno", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Takeyasu", "name": null }, { "creator_type": "author", "first_name": "Masayuki", "last_name": "Shirasawa", "name": null }, { "creator_type": "author", "first_name": "Kenta", "last_name": "Nakama", "name": null }, { "creator_type": "author", "first_name": "Keiju", "last_name": "Aokage", "name": null }, { "creator_type": "author", "first_name": "Jun", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Genichiro", "last_name": "Ishii", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Kuwata", "name": null }, { "creator_type": "author", "first_name": "Naoya", "last_name": "Sakamoto", "name": null }, { "creator_type": "author", "first_name": "Masahito", "last_name": "Kawazu", "name": null }, { "creator_type": "author", "first_name": "Toshihide", "last_name": "Ueno", "name": null }, { "creator_type": "author", "first_name": "Taisuke", "last_name": "Mori", "name": null }, { "creator_type": "author", "first_name": "Naoya", "last_name": "Yamazaki", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Tsuboi", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null }, { "creator_type": "author", "first_name": "Takahiro", "last_name": "Kinoshita", "name": null }, { "creator_type": "author", "first_name": "Toshihiko", "last_name": "Doi", "name": null }, { "creator_type": "author", "first_name": "Kohei", "last_name": "Shitara", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Mano", "name": null }, { "creator_type": "author", "first_name": "Hiroyoshi", "last_name": "Nishikawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.ccell.2022.01.001" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "35090594" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Biomarkers, Tumor", "descriptor_ui": "D014408", "major_topic": false }, { "descriptor": "CD8-Positive T-Lymphocytes", "descriptor_ui": "D018414", "major_topic": false }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Disease Models, Animal", "descriptor_ui": "D004195", "major_topic": false }, { "descriptor": "Fluorescent Antibody Technique", "descriptor_ui": "D005455", "major_topic": false }, { "descriptor": "Gene Expression Regulation, Neoplastic", "descriptor_ui": "D015972", "major_topic": true }, { "descriptor": "Glycolysis", "descriptor_ui": "D006019", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Immune Checkpoint Inhibitors", "descriptor_ui": "D000082082", "major_topic": false }, { "descriptor": "Immune Checkpoint Proteins", "descriptor_ui": "D000082102", "major_topic": false }, { "descriptor": "Immunophenotyping", "descriptor_ui": "D016130", "major_topic": false }, { "descriptor": "Lactic Acid", "descriptor_ui": "D019344", "major_topic": false }, { "descriptor": "Lymphocyte Activation", "descriptor_ui": "D008213", "major_topic": false }, { "descriptor": "Lymphocyte Count", "descriptor_ui": "D018655", "major_topic": false }, { "descriptor": "Lymphocytes, Tumor-Infiltrating", "descriptor_ui": "D016246", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Molecular Targeted Therapy", "descriptor_ui": "D058990", "major_topic": false }, { "descriptor": "Prognosis", "descriptor_ui": "D011379", "major_topic": false }, { "descriptor": "Programmed Cell Death 1 Receptor", "descriptor_ui": "D061026", "major_topic": false }, { "descriptor": "T-Lymphocytes, Regulatory", "descriptor_ui": "D050378", "major_topic": false }, { "descriptor": "Treatment Outcome", "descriptor_ui": "D016896", "major_topic": false }, { "descriptor": "Tumor Microenvironment", "descriptor_ui": "D059016", "major_topic": false } ], "publication": { "conference_name": null, "date": "2022 Feb 14", "date_precision": "day", "issue": "2", "normalized_date": "2022-02-14", "pages": "201-218.e9", "proceedings_title": null, "publisher": "", "title": "Cancer cell", "volume": "40", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Lactic acid promotes PD-1 expression in regulatory T cells in highly glycolytic tumor microenvironments.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The proliferation and differentiation of skeletal muscle cells are usually controlled by serum components. Myogenic differentiation is induced by a reduction of serum components in vitro. It has been recently reported that serum contains not only various growth factors with specific actions on the proliferation and differentiation of myogenic cells, but also exogenous exosomes, the function of which is poorly understood in myogenesis. We have found that exosomes in fetal bovine serum are capable of exerting an inhibitive effect on the differentiation of C2C12 myogenic cells in vitro. In this process of inhibition, the downregulation of Tceal5 and Tceal7 genes was observed. Expression of these genes is specifically increased in direct proportion to myogenic differentiation. Loss- or gain- of function studies with Tceal5 and Tceal7 indicated that they have the potential to regulate myogenic differentiation via exosomes in fetal bovine serum.", "classifications": [ { "id": "Yamamoto", "label": "Group Yamamoto", "parent": "Toyoshima", "type": "group" }, { "id": "Toyoshima", "label": "Team Toyoshima", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Aika", "last_name": "Sawada", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Takahiko", "last_name": "Sato", "name": null } ], "identifiers": { "doi": { "normalized": "10.3390/ijms23042036" }, "pmcid": { "normalized": "PMC8877866" }, "pmid": { "normalized": "35216152" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": true }, { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "Exosomes", "descriptor_ui": "D055354", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Myoblasts", "descriptor_ui": "D032446", "major_topic": true }, { "descriptor": "Nuclear Proteins", "descriptor_ui": "D009687", "major_topic": false }, { "descriptor": "Serum Albumin, Bovine", "descriptor_ui": "D012710", "major_topic": false }, { "descriptor": "Transcription Factors", "descriptor_ui": "D014157", "major_topic": true } ], "publication": { "conference_name": null, "date": "2022 Feb 12", "date_precision": "day", "issue": "4", "normalized_date": "2022-02-12", "pages": "2036", "proceedings_title": null, "publisher": "", "title": "International journal of molecular sciences", "volume": "23", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Tceal5 and Tceal7 Function in C2C12 Myogenic Differentiation via Exosomes in Fetal Bovine Serum.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Triple-negative breast cancer (TNBC) is a highly aggressive cancer for which targeted therapeutic agents are limited. Growing evidence suggests that TNBC originates from breast cancer stem cells (BCSCs), and elucidation of the molecular mechanisms controlling BCSC proliferation will be crucial for new drug development. We have previously reported that the lysosphingolipid sphingosine-1-phosphate mediates the CSC phenotype, which can be identified as the ALDH-positive cell population in several types of human cancer cell lines. In this study, we have investigated additional lipid receptors upregulated in BCSCs. We found that lysophosphatidic acid (LPA) receptor 3 was highly expressed in ALDH-positive TNBC cells. The LPAR3 antagonist inhibited the increase in ALDH-positive cells after LPA treatment. Mechanistically, the LPA-induced increase in ALDH-positive cells was dependent on intracellular calcium ion (Ca(2+)), and the increase in Ca(2+) was suppressed by a selective inhibitor of transient receptor potential cation channel subfamily C member 3 (TRPC3). Moreover, IL-8 production was involved in the LPA response via the activation of the Ca(2+)-dependent transcriptional factor nuclear factor of activated T cells. Taken together, our findings provide new insights into the lipid-mediated regulation of BCSCs via the LPA-TRPC3 signaling axis and suggest several potential therapeutic targets for TNBC.", "classifications": [ { "id": "Nishida", "label": "Group Nishida", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Naoya", "last_name": "Hirata", "name": null }, { "creator_type": "author", "first_name": "Shigeru", "last_name": "Yamada", "name": null }, { "creator_type": "author", "first_name": "Shota", "last_name": "Yanagida", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Ono", "name": null }, { "creator_type": "author", "first_name": "Yukuto", "last_name": "Yasuhiko", "name": null }, { "creator_type": "author", "first_name": "Motohiro", "last_name": "Nishida", "name": null }, { "creator_type": "author", "first_name": "Yasunari", "last_name": "Kanda", "name": null } ], "identifiers": { "doi": { "normalized": "10.3390/ijms23041967" }, "pmcid": { "normalized": "PMC8877950" }, "pmid": { "normalized": "35216080" } }, "mesh": [ { "descriptor": "Breast", "descriptor_ui": "D001940", "major_topic": false }, { "descriptor": "Calcium", "descriptor_ui": "D002118", "major_topic": false }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Epithelial-Mesenchymal Transition", "descriptor_ui": "D058750", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Gene Expression Regulation, Neoplastic", "descriptor_ui": "D015972", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Interleukin-8", "descriptor_ui": "D016209", "major_topic": false }, { "descriptor": "Lysophospholipids", "descriptor_ui": "D008246", "major_topic": false }, { "descriptor": "Neoplastic Stem Cells", "descriptor_ui": "D014411", "major_topic": false }, { "descriptor": "Receptors, Lysophosphatidic Acid", "descriptor_ui": "D049368", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Sphingosine", "descriptor_ui": "D013110", "major_topic": false }, { "descriptor": "Triple Negative Breast Neoplasms", "descriptor_ui": "D064726", "major_topic": false }, { "descriptor": "TRPC Cation Channels", "descriptor_ui": "D050052", "major_topic": false } ], "publication": { "conference_name": null, "date": "2022 Feb 10", "date_precision": "day", "issue": "4", "normalized_date": "2022-02-10", "pages": "1967", "proceedings_title": null, "publisher": "", "title": "International journal of molecular sciences", "volume": "23", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Lysophosphatidic Acid Promotes the Expansion of Cancer Stem Cells via TRPC3 Channels in Triple-Negative Breast Cancer.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Herein we report the first chiral Au(10) nanoclusters stabilized by chiral bis N-heterocyclic carbene (bisNHC) ligands. ESI-MS and single-crystal X-ray crystallography confirmed the molecular formula to be [Au(10)(bisNHC)(4)Br(2)](O(2)CCF(3))(2). The chiral Au(10) nanocluster adopts a linear edge-shared tetrahedral geometry with a prolate shape. DFT calculations provide insight into the electronic structure, optical absorption, and circular dichroism (CD) characteristics of this unique Au(10) nanocluster. CD spectra demonstrate chirality transfer from the chiral bisNHC ligand to the inner Au(10) nanocluster core. Examination of ESI-MS and UV-vis spectra show that cluster [Au(9)(bisNHC)(4)Br]Br(2) is formed initially and then transformed into the Au(10) nanocluster in solution.", "classifications": [ { "id": "Nanbo", "label": "Group Nanbo", "parent": "Tsuchiya", "type": "group" }, { "id": "Tsuchiya", "label": "Team Tsuchiya", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Renee W. Y.", "last_name": "Man", "name": null }, { "creator_type": "author", "first_name": "Hong", "last_name": "Yi", "name": null }, { "creator_type": "author", "first_name": "Sami", "last_name": "Malola", "name": null }, { "creator_type": "author", "first_name": "Shinjiro", "last_name": "Takano", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Tsukuda", "name": null }, { "creator_type": "author", "first_name": "Hannu", "last_name": "Hakkinen", "name": null }, { "creator_type": "author", "first_name": "Masakazu", "last_name": "Nambo", "name": null }, { "creator_type": "author", "first_name": "Cathleen M.", "last_name": "Crudden", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/jacs.1c11857" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "35100506" } }, "mesh": [], "publication": { "conference_name": null, "date": "2022 Feb 9", "date_precision": "day", "issue": "5", "normalized_date": "2022-02-09", "pages": "2056-2061", "proceedings_title": null, "publisher": "", "title": "Journal of the American Chemical Society", "volume": "144", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Synthesis and Characterization of Enantiopure Chiral Bis NHC-Stabilized Edge-Shared Au(10) Nanocluster with Unique Prolate Shape.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Oral glucose ingestion induces systemic changes of many blood metabolites related not only to glucose, but also other metabolites such as amino acids and lipids through many blood hormones. However, the detailed temporal changes in the concentrations of comprehensive metabolites and hormones over a long time by oral glucose ingestion are uncharacterized. We measured 83 metabolites and 7 hormones in 20 healthy human subjects in response to glucose ingestion. We characterized temporal patterns of blood molecules by four features: (i) the decomposability into \"amplitude\" and \"rate\" components, (ii) the similarity of temporal patterns among individuals, (iii) the relation of molecules over time among individuals, and (iv) the similarity of temporal patterns among molecules. Glucose and glucose metabolism-related hormones indicated a rapid increase, and citrulline and lipids, which indicated a rapid decrease, returned to fasting levels faster than amino acids. Compared to glucose metabolism-related molecules and lipids, amino acids showed similar temporal patterns among individuals. The four features of temporal patterns of blood molecules by oral glucose ingestion characterize the differences among individuals and among molecules.", "classifications": [ { "id": "Kuroda", "label": "Group Kuroda", "parent": "Kuroda", "type": "group" }, { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Suguru", "last_name": "Fujita", "name": null }, { "creator_type": "author", "first_name": "Yasuaki", "last_name": "Karasawa", "name": null }, { "creator_type": "author", "first_name": "Masashi", "last_name": "Fujii", "name": null }, { "creator_type": "author", "first_name": "Ken-Ichi", "last_name": "Hironaka", "name": null }, { "creator_type": "author", "first_name": "Shinsuke", "last_name": "Uda", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Kubota", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Inoue", "name": null }, { "creator_type": "author", "first_name": "Yohei", "last_name": "Sumitomo", "name": null }, { "creator_type": "author", "first_name": "Akiyoshi", "last_name": "Hirayama", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Kuroda", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41540-022-00213-0" }, "pmcid": { "normalized": "PMC8826934" }, "pmid": { "normalized": "35136093" } }, "mesh": [ { "descriptor": "Blood Glucose", "descriptor_ui": "D001786", "major_topic": true }, { "descriptor": "Eating", "descriptor_ui": "D004435", "major_topic": false }, { "descriptor": "Glucose", "descriptor_ui": "D005947", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Insulin", "descriptor_ui": "D007328", "major_topic": false } ], "publication": { "conference_name": null, "date": "2022 Feb 8", "date_precision": "day", "issue": "1", "normalized_date": "2022-02-08", "pages": "6", "proceedings_title": null, "publisher": "", "title": "NPJ systems biology and applications", "volume": "8", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Four features of temporal patterns characterize similarity among individuals and molecules by glucose ingestion in humans.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: Approximately 20% of lung adenocarcinoma (LUAD) is negative for the lineage-specific oncogene Thyroid transcription factor 1 (TTF-1) and exhibits worse clinical outcome with a low frequency of actionable genomic alterations. To identify molecular features associated with TTF-1-negative LUAD, we compared the transcriptomic and proteomic profiles of LUAD cell lines. SRGN , a chondroitin sulfate proteoglycan Serglycin, was identified as a markedly overexpressed gene in TTF-1-negative LUAD. We therefore investigated the roles and regulation of SRGN in TTF-1-negative LUAD. METHODS: Proteomic and metabolomic analyses of 41 LUAD cell lines were done using mass spectrometry. The function of SRGN was investigated in 3 TTF-1-negative and 4 TTF-1-positive LUAD cell lines and in a syngeneic mouse model (n = 5 to 8 mice per group). Expression of SRGN was evaluated in 94 and 105 surgically resected LUAD tumor specimens using immunohistochemistry. All statistical tests were 2-sided. RESULTS: SRGN was markedly overexpressed at mRNA and protein levels in TTF-1-negative LUAD cell lines (P < .001 for both mRNA and protein levels). Expression of SRGN in LUAD tumor tissue was associated with poor outcome (hazard ratio = 4.22, 95% confidence interval = 1.12 to 15.86, likelihood ratio test, P = .03), and with higher expression of Programmed cell death 1 ligand 1 (PD-L1) in tumor cells and higher infiltration of Programmed cell death protein 1-positive lymphocytes. SRGN regulated expression of PD-L1 as well as proinflammatory cytokines, including Interleukin-6, Interleukin-8, and C-X-C motif chemokine 1 in LUAD cell lines; increased migratory and invasive properties of LUAD cells and fibroblasts; and enhanced angiogenesis. SRGN was induced by DNA demethylation resulting from Nicotinamide N-methyltransferase-mediated impairment of methionine metabolism. CONCLUSIONS: Our findings suggest that SRGN plays a pivotal role in tumor-stromal interaction and reprogramming into an aggressive and immunosuppressive tumor microenvironment in TTF-1-negative LUAD.", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Ichidai", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Delphine", "last_name": "Dayde", "name": null }, { "creator_type": "author", "first_name": "Mei Chee", "last_name": "Tai", "name": null }, { "creator_type": "author", "first_name": "Haruki", "last_name": "Mori", "name": null }, { "creator_type": "author", "first_name": "Luisa M.", "last_name": "Solis", "name": null }, { "creator_type": "author", "first_name": "Satyendra C.", "last_name": "Tripathi", "name": null }, { "creator_type": "author", "first_name": "Johannes F.", "last_name": "Fahrmann", "name": null }, { "creator_type": "author", "first_name": "Nese", "last_name": "Unver", "name": null }, { "creator_type": "author", "first_name": "Gargy", "last_name": "Parhy", "name": null }, { "creator_type": "author", "first_name": "Rekha", "last_name": "Jain", "name": null }, { "creator_type": "author", "first_name": "Edwin R.", "last_name": "Parra", "name": null }, { "creator_type": "author", "first_name": "Yoshiko", "last_name": "Murakami", "name": null }, { "creator_type": "author", "first_name": "Clemente", "last_name": "Aguilar-Bonavides", "name": null }, { "creator_type": "author", "first_name": "Barbara", "last_name": "Mino", "name": null }, { "creator_type": "author", "first_name": "Muge", "last_name": "Celiktas", "name": null }, { "creator_type": "author", "first_name": "Dilsher", "last_name": "Dhillon", "name": null }, { "creator_type": "author", "first_name": "Julian Phillip", "last_name": "Casabar", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Nakatochi", "name": null }, { "creator_type": "author", "first_name": "Francesco", "last_name": "Stingo", "name": null }, { "creator_type": "author", "first_name": "Veera", "last_name": "Baladandayuthapani", "name": null }, { "creator_type": "author", "first_name": "Hong", "last_name": "Wang", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Katayama", "name": null }, { "creator_type": "author", "first_name": "Jennifer B.", "last_name": "Dennison", "name": null }, { "creator_type": "author", "first_name": "Philip L.", "last_name": "Lorenzi", "name": null }, { "creator_type": "author", "first_name": "Kim-Anh", "last_name": "Do", "name": null }, { "creator_type": "author", "first_name": "Junya", "last_name": "Fujimoto", "name": null }, { "creator_type": "author", "first_name": "Carmen", "last_name": "Behrens", "name": null }, { "creator_type": "author", "first_name": "Edwin J.", "last_name": "Ostrin", "name": null }, { "creator_type": "author", "first_name": "Jaime", "last_name": "Rodriguez-Canales", "name": null }, { "creator_type": "author", "first_name": "Tetsunari", "last_name": "Hase", "name": null }, { "creator_type": "author", "first_name": "Takayuki", "last_name": "Fukui", "name": null }, { "creator_type": "author", "first_name": "Taisuke", "last_name": "Kajino", "name": null }, { "creator_type": "author", "first_name": "Seiichi", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null }, { "creator_type": "author", "first_name": "Waki", "last_name": "Hosoda", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Kawaguchi", "name": null }, { "creator_type": "author", "first_name": "Kohei", "last_name": "Yokoi", "name": null }, { "creator_type": "author", "first_name": "Toyofumi F.", "last_name": "Chen-Yoshikawa", "name": null }, { "creator_type": "author", "first_name": "Yoshinori", "last_name": "Hasegawa", "name": null }, { "creator_type": "author", "first_name": "Adi F.", "last_name": "Gazdar", "name": null }, { "creator_type": "author", "first_name": "Ignacio I.", "last_name": "Wistuba", "name": null }, { "creator_type": "author", "first_name": "Samir", "last_name": "Hanash", "name": null }, { "creator_type": "author", "first_name": "Ayumu", "last_name": "Taguchi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1093/jnci/djab183" }, "pmcid": { "normalized": "PMC8826620" }, "pmid": { "normalized": "34524427" } }, "mesh": [ { "descriptor": "Adenocarcinoma of Lung", "descriptor_ui": "D000077192", "major_topic": true }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "DNA-Binding Proteins", "descriptor_ui": "D004268", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Lung Neoplasms", "descriptor_ui": "D008175", "major_topic": true }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Phenotype", "descriptor_ui": "D010641", "major_topic": false }, { "descriptor": "Proteoglycans", "descriptor_ui": "D011509", "major_topic": true }, { "descriptor": "Proteomics", "descriptor_ui": "D040901", "major_topic": false }, { "descriptor": "Thyroid Nuclear Factor 1", "descriptor_ui": "D000074482", "major_topic": false }, { "descriptor": "Transcription Factors", "descriptor_ui": "D014157", "major_topic": true }, { "descriptor": "Tumor Microenvironment", "descriptor_ui": "D059016", "major_topic": false }, { "descriptor": "Vesicular Transport Proteins", "descriptor_ui": "D033921", "major_topic": true } ], "publication": { "conference_name": null, "date": "2022 Feb 7", "date_precision": "day", "issue": "2", "normalized_date": "2022-02-07", "pages": "290-301", "proceedings_title": null, "publisher": "", "title": "Journal of the National Cancer Institute", "volume": "114", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "SRGN-Triggered Aggressive and Immunosuppressive Phenotype in a Subset of TTF-1-Negative Lung Adenocarcinomas.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Astrocytes are thought to play a crucial role in providing structure to the spinal cord and maintaining efficient synaptic function and metabolism because their fine processes envelop the synapses of neurons and form many neuronal networks within the central nervous system (CNS). To investigate whether putative astrocytes and putative neurons distributed on the ventral horn play a role in the modulation of lumbar locomotor central pattern generator (CPG) networks, we used extracellular recording and optical imaging techniques and recorded the neural output from the left L5 ventral root and the calcium activity of putative astrocytes and neurons in the L5 ventral horn at the same time when activating an isolated L1-L5 spinal cord preparation from rats aged 0-2 days. Optical measurements detected cells that showed a fluorescence intensity change under all experimental conditions, namely, (1) 5-HT + NMDA, (2) TTX, and (3) TTX + Low K(+). These cells were semiautomatically identified using an in-house MATLAB-based program, as putative astrocytes and neurons according to the cell classification, i.e., increased or decreased fluorescence intensity change (DeltaF/F0), and subjective judgment based on their soma size. Coherence and its phase were calculated according to the calcium activity of the putative astrocytes and putative neurons, and neural output was calculated during fictive locomotion with in-house MATLAB-based programs. We found that the number of putative astrocytes activated by applying low K(+) tends not to differ from that activated by applying the protease-activated receptor 1 (PAR1) selective agonist TFLLR-NH2 (TFLLR). Moreover, the calcium activity of several putative astrocytes and neurons synchronized with locomotor-like activity at a frequency range below 0.5 Hz and the time lag between peaks of cellular calcium activity and locomotor-like activity ranged from -1000 to + 1000 ms. These findings presumably indicates that these putative astrocytes and neurons in the left L5 ventral horn require -1000 to + 1000 ms to communicate with lumbar CPG networks and maintain efficient synaptic function and metabolism in activated lumbar CPG networks. This finding suggests the possibility that putative astrocytic and neuronal cells in the L5 ventral horn contribute to generating the rhythms and patterns of locomotor-like activity by activated CPG networks in the first to fifth lumbar spinal cord.", "classifications": [ { "id": "Yokota", "label": "Group Yokota", "parent": "Enomoto", "type": "group" }, { "id": "Enomoto", "label": "Team Enomoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Itaru", "last_name": "Yazawa", "name": null }, { "creator_type": "author", "first_name": "Shuntaro", "last_name": "Okazaki", "name": null }, { "creator_type": "author", "first_name": "Shigefumi", "last_name": "Yokota", "name": null }, { "creator_type": "author", "first_name": "Kotaro", "last_name": "Takeda", "name": null }, { "creator_type": "author", "first_name": "Isato", "last_name": "Fukushi", "name": null }, { "creator_type": "author", "first_name": "Masashi", "last_name": "Yoshizawa", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Onimaru", "name": null }, { "creator_type": "author", "first_name": "Yasumasa", "last_name": "Okada", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.neulet.2021.136421" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "34968723" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Anterior Horn Cells", "descriptor_ui": "D000870", "major_topic": false }, { "descriptor": "Astrocytes", "descriptor_ui": "D001253", "major_topic": false }, { "descriptor": "Calcium Signaling", "descriptor_ui": "D020013", "major_topic": true }, { "descriptor": "Central Pattern Generators", "descriptor_ui": "D063226", "major_topic": false }, { "descriptor": "Locomotion", "descriptor_ui": "D008124", "major_topic": true }, { "descriptor": "N-Methylaspartate", "descriptor_ui": "D016202", "major_topic": false }, { "descriptor": "Oligopeptides", "descriptor_ui": "D009842", "major_topic": false }, { "descriptor": "Potassium", "descriptor_ui": "D011188", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Rats, Wistar", "descriptor_ui": "D017208", "major_topic": false }, { "descriptor": "Serotonin", "descriptor_ui": "D012701", "major_topic": false }, { "descriptor": "Tetrodotoxin", "descriptor_ui": "D013779", "major_topic": false } ], "publication": { "conference_name": null, "date": "2022 Feb 6", "date_precision": "day", "issue": "", "normalized_date": "2022-02-06", "pages": "136421", "proceedings_title": null, "publisher": "", "title": "Neuroscience letters", "volume": "771", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Coherence analysis of the calcium activity of putative astrocytic and neuronal cells on the L5 ventral horn and neural output in activated lumbar CPG networks.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The vomeronasal system plays an essential role in sensing various environmental chemical cues. Here we show that mice exposed to blood and, consequently, hemoglobin results in the activation of vomeronasal sensory neurons expressing a specific vomeronasal G protein-coupled receptor, Vmn2r88, which is mediated by the interaction site, Gly17, on hemoglobin. The hemoglobin signal reaches the medial amygdala (MeA) in both male and female mice. However, it activates the dorsal part of ventromedial hypothalamus (VMHd) only in lactating female mice. As a result, in lactating mothers, hemoglobin enhances digging and rearing behavior. Manipulation of steroidogenic factor 1 (SF1)-expressing neurons in the VMHd is sufficient to induce the hemoglobin-mediated behaviors. Our results suggest that the oxygen-carrier hemoglobin plays a role as a chemosensory signal, eliciting behavioral responses in mice in a state-dependent fashion.", "classifications": [ { "id": "Miyamichi", "label": "Group Miyamichi", "parent": "Enomoto", "type": "group" }, { "id": "Enomoto", "label": "Team Enomoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Takuya", "last_name": "Osakada", "name": null }, { "creator_type": "author", "first_name": "Takayuki", "last_name": "Abe", "name": null }, { "creator_type": "author", "first_name": "Takumi", "last_name": "Itakura", "name": null }, { "creator_type": "author", "first_name": "Hiromi", "last_name": "Mori", "name": null }, { "creator_type": "author", "first_name": "Kentaro K.", "last_name": "Ishii", "name": null }, { "creator_type": "author", "first_name": "Ryo", "last_name": "Eguchi", "name": null }, { "creator_type": "author", "first_name": "Ken", "last_name": "Murata", "name": null }, { "creator_type": "author", "first_name": "Kosuke", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Sachiko", "last_name": "Haga-Yamanaka", "name": null }, { "creator_type": "author", "first_name": "Hiroko", "last_name": "Kimoto", "name": null }, { "creator_type": "author", "first_name": "Yoshihiro", "last_name": "Yoshihara", "name": null }, { "creator_type": "author", "first_name": "Kazunari", "last_name": "Miyamichi", "name": null }, { "creator_type": "author", "first_name": "Kazushige", "last_name": "Touhara", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41467-022-28118-w" }, "pmcid": { "normalized": "PMC8814178" }, "pmid": { "normalized": "35115521" } }, "mesh": [ { "descriptor": "Amygdala", "descriptor_ui": "D000679", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "beta-Globins", "descriptor_ui": "D055544", "major_topic": false }, { "descriptor": "Biomarkers", "descriptor_ui": "D015415", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Hemoglobins", "descriptor_ui": "D006454", "major_topic": false }, { "descriptor": "In Situ Hybridization", "descriptor_ui": "D017403", "major_topic": false }, { "descriptor": "Lactation", "descriptor_ui": "D007774", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred BALB C", "descriptor_ui": "D008807", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Motor Activity", "descriptor_ui": "D009043", "major_topic": false }, { "descriptor": "Proto-Oncogene Proteins c-fos", "descriptor_ui": "D016760", "major_topic": false }, { "descriptor": "Receptors, G-Protein-Coupled", "descriptor_ui": "D043562", "major_topic": false }, { "descriptor": "Sensory Receptor Cells", "descriptor_ui": "D011984", "major_topic": false }, { "descriptor": "Steroidogenic Factor 1", "descriptor_ui": "D054339", "major_topic": false }, { "descriptor": "Ventromedial Hypothalamic Nucleus", "descriptor_ui": "D014697", "major_topic": false }, { "descriptor": "Vomeronasal Organ", "descriptor_ui": "D019147", "major_topic": false } ], "publication": { "conference_name": null, "date": "2022 Feb 3", "date_precision": "day", "issue": "1", "normalized_date": "2022-02-03", "pages": "556", "proceedings_title": null, "publisher": "", "title": "Nature communications", "volume": "13", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Hemoglobin in the blood acts as a chemosensory signal via the mouse vomeronasal system.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Natural killer (NK) cells lyse invading tumor cells to limit metastatic growth in the lung, but how some cancers evade this host protective mechanism to establish a growing lesion is unknown. Here, we have combined ultra-sensitive bioluminescence imaging with intravital two-photon microscopy involving genetically encoded biosensors to examine this question. NK cells eliminated disseminated tumor cells from the lung within 24 hr of arrival, but not thereafter. Intravital dynamic imaging revealed that 50% of NK-tumor cell encounters lead to tumor cell death in the first 4 hr after tumor cell arrival, but after 24 hr of arrival, nearly 100% of the interactions result in the survival of the tumor cell. During this 24-hr period, the probability of ERK activation in NK cells upon encountering the tumor cells was decreased from 68% to 8%, which correlated with the loss of the activating ligand CD155/PVR/Necl5 from the tumor cell surface. Thus, by quantitatively visualizing, the NK-tumor cell interaction at the early stage of metastasis, we have revealed the crucial parameters of NK cell immune surveillance in the lung.", "classifications": [], "creators": [ { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Ichise", "name": null }, { "creator_type": "author", "first_name": "Shoko", "last_name": "Tsukamoto", "name": null }, { "creator_type": "author", "first_name": "Tsuyoshi", "last_name": "Hirashima", "name": null }, { "creator_type": "author", "first_name": "Yoshinobu", "last_name": "Konishi", "name": null }, { "creator_type": "author", "first_name": "Choji", "last_name": "Oki", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Tsukiji", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Iwano", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Miyawaki", "name": null }, { "creator_type": "author", "first_name": "Kenta", "last_name": "Sumiyama", "name": null }, { "creator_type": "author", "first_name": "Kenta", "last_name": "Terai", "name": null }, { "creator_type": "author", "first_name": "Michiyuki", "last_name": "Matsuda", "name": null } ], "identifiers": { "doi": { "normalized": "10.7554/elife.76269" }, "pmcid": { "normalized": "PMC8849286" }, "pmid": { "normalized": "35113018" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Biosensing Techniques", "descriptor_ui": "D015374", "major_topic": false }, { "descriptor": "Cell Communication", "descriptor_ui": "D002450", "major_topic": false }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Immunologic Surveillance", "descriptor_ui": "D007157", "major_topic": true }, { "descriptor": "Intravital Microscopy", "descriptor_ui": "D000069416", "major_topic": false }, { "descriptor": "Killer Cells, Natural", "descriptor_ui": "D007694", "major_topic": false }, { "descriptor": "Luminescent Proteins", "descriptor_ui": "D008164", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred BALB C", "descriptor_ui": "D008807", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Neoplasm Metastasis", "descriptor_ui": "D009362", "major_topic": false }, { "descriptor": "Neoplastic Cells, Circulating", "descriptor_ui": "D009360", "major_topic": false } ], "publication": { "conference_name": null, "date": "2022 Feb 3", "date_precision": "day", "issue": "", "normalized_date": "2022-02-03", "pages": "e76269", "proceedings_title": null, "publisher": "", "title": "eLife", "volume": "11", "year": 2022 }, "ssbd": { "database": [], "repository": [ "ssbd-repos-000162" ] }, "title": "Functional visualization of NK cell-mediated killing of metastatic single tumor cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Intercellular signals induce various cellular responses, including growth, proliferation, and differentiation, via the dynamic processes of signal transduction pathways. For cell fate decisions, ligand-binding induces the phosphorylation of ERBB receptors, which in turn activate downstream molecules. The ERBB family includes four subtypes, which diverged through two gene duplications from a common ancestor. Differences in the expression patterns of the subtypes have been reported between different organs in the human body. However, how these different expression properties influence the diverse phosphorylation levels of ERBB proteins is not well understood. Here we study the origin of the phosphorylation responses by experimental and mathematical analyses. The experimental measurements clarified that the phosphorylation levels heavily depend on the ERBB expression profiles. We developed a mathematical model consisting of the four subtypes as monomers, homodimers, and heterodimers and estimated the rate constants governing the phosphorylation responses from the experimental data. To understand the origin of the diversity, we analyzed the effects of the expression levels and reaction rates of the ERBB subtypes on the diversity. The difference in phosphorylation rates between ERBB subtypes showed a much greater contribution to the diversity than did the dimerization rates. This result implies that divergent evolution in phosphorylation reactions rather than in dimerization reactions after whole genome duplications was essential for increasing the diversity of the phosphorylation responses.", "classifications": [ { "id": "JPMJCR1922", "label": "JPMJCR1922", "researcher": "Mototsugu Eiraku", "type": "grant" }, { "id": "Eiraku", "label": "Group Eiraku", "parent": "Eiraku", "type": "group" }, { "id": "Mochizuki", "label": "Group Mochizuki", "parent": "Eiraku", "type": "group" }, { "id": "Eiraku", "label": "Team Eiraku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Takashi", "last_name": "Okada", "name": null }, { "creator_type": "author", "first_name": "Hiraku", "last_name": "Miyagi", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Sako", "name": null }, { "creator_type": "author", "first_name": "Michio", "last_name": "Hiroshima", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Mochizuki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.bpj.2021.12.031" }, "pmcid": { "normalized": "PMC8822607" }, "pmid": { "normalized": "34958777" } }, "mesh": [ { "descriptor": "Erb-b2 Receptor Tyrosine Kinases", "descriptor_ui": "D018719", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Phosphorylation", "descriptor_ui": "D010766", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": true } ], "publication": { "conference_name": null, "date": "2022 Feb 1", "date_precision": "day", "issue": "3", "normalized_date": "2022-02-01", "pages": "470-480", "proceedings_title": null, "publisher": "", "title": "Biophysical journal", "volume": "121", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Origin of diverse phosphorylation patterns in the ERBB system.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "OBJECTIVES: To examine the severe ocular complications associated with contact lens wearing in Japan. METHOD: A questionnaire was sent to 964 ophthalmologist training facilities inquiring for cases of contact lens-associated complications from April 2016 to March 2018. The inclusion criteria were as follows: (1) corrected distance visual acuity 2; and R-Sn-H, n > 1) exist in many organisms. The highly nucleophilic nature of hydropersulfides and hydropolysulfides contributes to the potent antioxidant activities of polysulfide species that protect organisms against oxidative and electrophilic stresses. Recent Advances: Accumulating evidence suggests that organic polysulfides (R-Sn-R') readily undergo alkaline hydrolysis, which results in formation of both nucleophilic hydrosulfide/polysulfide (R-Sn-1H) and electrophilic sulfenic acid (R'SOH) species. Polysulfides maintain a steady-state equilibrium that is driven by hydrolysis even in aqueous physiological milieus. This unique property makes polysulfide chemistry and biology more complex than previously believed. Critical Issues: The hydrolysis equilibrium of polysulfides shifts to the right when electrophiles are present. Strong electrophilic alkylating agents (e.g., monobromobimane) greatly enhance polysulfide hydrolysis, which leads to increased polysulfide degradation and artifactual formation of bis-S-bimane adducts in the absence of free hydrogen sulfide. The finding that hydroxyl group-containing substances such as tyrosine efficiently protected polysulfides from hydrolysis led to development of the new alkylating agent, N-iodoacetyl l-tyrosine methyl ester (TME-IAM). TME-IAM efficiently and specifically traps and stabilizes hydropolysulfides and protects polysulfide chains from hydrolysis, and, when used with mass spectrometry, TME-IAM allows speciation of the reactive sulfur metabolome. In addition, the polyethylene glycol-conjugated maleimide-labeling gel shift assay, which relies on unique hydrolysis equilibrium of polysulfides, will be a reliable technique for proteomics of polysulfide-containing proteins. Future Directions: Using precise methodologies to achieve a better understanding of the occurrence and metabolism of polysulfide species is necessary to gain insights into the undefined biology of polysulfide species. Antioxid. Redox Signal. 36, 327-336.", "classifications": [ { "id": "JPMJCR2024", "label": "JPMJCR2024", "researcher": "Motohiro Nishida", "type": "grant" }, { "id": "Akaike", "label": "Group Akaike", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Group Nishida", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Tomohiro", "last_name": "Sawa", "name": null }, { "creator_type": "author", "first_name": "Tsuyoshi", "last_name": "Takata", "name": null }, { "creator_type": "author", "first_name": "Tetsuro", "last_name": "Matsunaga", "name": null }, { "creator_type": "author", "first_name": "Hideshi", "last_name": "Ihara", "name": null }, { "creator_type": "author", "first_name": "Hozumi", "last_name": "Motohashi", "name": null }, { "creator_type": "author", "first_name": "Takaaki", "last_name": "Akaike", "name": null } ], "identifiers": { "doi": { "normalized": "10.1089/ars.2021.0170" }, "pmcid": { "normalized": "PMC8865625" }, "pmid": { "normalized": "34409860" } }, "mesh": [ { "descriptor": "Bridged Bicyclo Compounds", "descriptor_ui": "D001643", "major_topic": false }, { "descriptor": "Hydrolysis", "descriptor_ui": "D006868", "major_topic": false }, { "descriptor": "Proteomics", "descriptor_ui": "D040901", "major_topic": false }, { "descriptor": "Sulfides", "descriptor_ui": "D013440", "major_topic": true }, { "descriptor": "Sulfur", "descriptor_ui": "D013455", "major_topic": true } ], "publication": { "conference_name": null, "date": "2022 Feb", "date_precision": "unknown", "issue": "4-6", "normalized_date": null, "pages": "327-336", "proceedings_title": null, "publisher": "", "title": "Antioxidants & redox signaling", "volume": "36", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Chemical Biology of Reactive Sulfur Species: Hydrolysis-Driven Equilibrium of Polysulfides as a Determinant of Physiological Functions.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Quantitative depth estimation of tumor invasion in early gastric cancer by scattering of circularly polarized light is computationally investigated using the Monte Carlo method. Using the optical parameters of the human stomach wall and its carcinoma, the intensity and circular polarization of light scattered from pseudo-healthy and cancerous tissues were calculated over a wide spectral range. Large differences in the circular polarization with opposite signs, together with the large intensity, are obtained at wavelengths 600 nm and 950 nm. At these two wavelengths, the sampling depth of the biological tissues can be modulated by tuning the detection angle. In bi-layered pseudo-tissues with a cancerous layer on a healthy layer and vice versa, the degree of circular polarization of scattered light shows systematic changes depending on the thickness and depth of the cancerous layer, which indicates the feasibility of in vivo quantitative estimation of cancer progression in early gastric cancer.", "classifications": [ { "id": "Kuchimaru", "label": "Group Kuchimaru", "parent": "Shintaku", "type": "group" }, { "id": "Shintaku", "label": "Team Shintaku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Nozomi", "last_name": "Nishizawa", "name": null }, { "creator_type": "author", "first_name": "Takahiro", "last_name": "Kuchimaru", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/jbio.202200062" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "35666013" } }, "mesh": [ { "descriptor": "Computer Simulation", "descriptor_ui": "D003198", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Monte Carlo Method", "descriptor_ui": "D009010", "major_topic": false }, { "descriptor": "Scattering, Radiation", "descriptor_ui": "D012542", "major_topic": false }, { "descriptor": "Stomach Neoplasms", "descriptor_ui": "D013274", "major_topic": true } ], "publication": { "conference_name": null, "date": "2022 Oct", "date_precision": "unknown", "issue": "10", "normalized_date": null, "pages": "e202200062", "proceedings_title": null, "publisher": "", "title": "Journal of biophotonics", "volume": "15", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Depth estimation of tumor invasion in early gastric cancer using scattering of circularly polarized light: Monte Carlo Simulation study.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The transcription factor NF-kappaB, which plays an important role in cell fate determination, is involved in the activation of super-enhancers (SEs). However, the biological functions of the NF-kappaB SEs in gene control are not fully elucidated. We investigated the characteristics of NF-kappaB-mediated SE activity using fluorescence imaging of RelA, single-cell transcriptome and chromatin accessibility analyses in anti-IgM-stimulated B cells. The formation of cell stimulation-induced nuclear RelA foci was abolished in the presence of hexanediol, suggesting an underlying process of liquid-liquid phase separation. The gained SEs induced a switch-like expression and enhanced cell-to-cell variability in transcriptional response. These properties were correlated with the number of gained cis-regulatory interactions, while switch-like gene induction was associated with the number of NF-kappaB binding sites in SE. Our study suggests that NF-kappaB SEs have an important role in the transcriptional regulation of B cells possibly through liquid condensate formation consisting of macromolecular interactions.", "classifications": [ { "id": "JPMJCR1926", "label": "JPMJCR1926", "researcher": "Hironobu Fujiwara", "type": "grant" }, { "id": "Fujiwara", "label": "Group Fujiwara", "parent": "Fujiwara", "type": "group" }, { "id": "Nikaido", "label": "Group Nikaido", "parent": "Fujiwara", "type": "group" }, { "id": "Fujiwara", "label": "Team Fujiwara", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Johannes N.", "last_name": "Wibisana", "name": null }, { "creator_type": "author", "first_name": "Takehiko", "last_name": "Inaba", "name": null }, { "creator_type": "author", "first_name": "Hisaaki", "last_name": "Shinohara", "name": null }, { "creator_type": "author", "first_name": "Noriko", "last_name": "Yumoto", "name": null }, { "creator_type": "author", "first_name": "Tetsutaro", "last_name": "Hayashi", "name": null }, { "creator_type": "author", "first_name": "Mana", "last_name": "Umeda", "name": null }, { "creator_type": "author", "first_name": "Masashi", "last_name": "Ebisawa", "name": null }, { "creator_type": "author", "first_name": "Itoshi", "last_name": "Nikaido", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Sako", "name": null }, { "creator_type": "author", "first_name": "Mariko", "last_name": "Okada", "name": null } ], "identifiers": { "doi": { "normalized": "10.1371/journal.pgen.1010235" }, "pmcid": { "normalized": "PMC9191726" }, "pmid": { "normalized": "35648786" } }, "mesh": [ { "descriptor": "Cell Nucleus", "descriptor_ui": "D002467", "major_topic": false }, { "descriptor": "Gene Expression Regulation", "descriptor_ui": "D005786", "major_topic": false }, { "descriptor": "NF-kappa B", "descriptor_ui": "D016328", "major_topic": true }, { "descriptor": "Protein Binding", "descriptor_ui": "D011485", "major_topic": false }, { "descriptor": "Regulatory Sequences, Nucleic Acid", "descriptor_ui": "D012045", "major_topic": false }, { "descriptor": "Transcription Factor RelA", "descriptor_ui": "D051996", "major_topic": true }, { "descriptor": "Transcriptional Activation", "descriptor_ui": "D015533", "major_topic": false } ], "publication": { "conference_name": null, "date": "2022 Jun", "date_precision": "unknown", "issue": "6", "normalized_date": null, "pages": "e1010235", "proceedings_title": null, "publisher": "", "title": "PLoS genetics", "volume": "18", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Enhanced transcriptional heterogeneity mediated by NF-kappaB super-enhancers.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Fluorescent probes are useful tools for the detection of sulfane sulfurs in biological systems. In this work, we report the development of SSP4, a widely used probe generated in our laboratory. We describe its evolution, preparation, and physical/chemical properties. Fluorescence analyses of SSP4 determined its high selectivity and sensitivity to sulfane sulfurs, even with the interfering presence of other species, such as amino acids and metal ions. Protocols for using SSP4 in a relatively quick and simple manner for the detection of persulfidated proteins, including papain, BSA, and GAPDH were developed. The method was then applied to human protein disulfide isomerase (PDI), leading to the discovery that persulfidation can occur at PDI's non-active site cysteines, and that PDI reductase activity is affected by sulfane sulfur treatment. Protocols for using SSP4 for the bioimaging of exogenous and endogenous sulfane sulfurs in different -cell lines were also established. These results should guide further applications of SSP4.", "classifications": [ { "id": "JPMJCR2024", "label": "JPMJCR2024", "researcher": "Motohiro Nishida", "type": "grant" }, { "id": "Akaike", "label": "Group Akaike", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Group Nishida", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Meg", "last_name": "Shieh", "name": null }, { "creator_type": "author", "first_name": "Xiang", "last_name": "Ni", "name": null }, { "creator_type": "author", "first_name": "Shi", "last_name": "Xu", "name": null }, { "creator_type": "author", "first_name": "Stephen P.", "last_name": "Lindahl", "name": null }, { "creator_type": "author", "first_name": "Moua", "last_name": "Yang", "name": null }, { "creator_type": "author", "first_name": "Tetsuro", "last_name": "Matsunaga", "name": null }, { "creator_type": "author", "first_name": "Robert", "last_name": "Flaumenhaft", "name": null }, { "creator_type": "author", "first_name": "Takaaki", "last_name": "Akaike", "name": null }, { "creator_type": "author", "first_name": "Ming", "last_name": "Xian", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.redox.2022.102433" }, "pmcid": { "normalized": "PMC9411671" }, "pmid": { "normalized": "35987086" } }, "mesh": [ { "descriptor": "Cysteine", "descriptor_ui": "D003545", "major_topic": false }, { "descriptor": "Fluorescent Dyes", "descriptor_ui": "D005456", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Oxidoreductases", "descriptor_ui": "D010088", "major_topic": false }, { "descriptor": "Papain", "descriptor_ui": "D010206", "major_topic": false }, { "descriptor": "Protein Disulfide-Isomerases", "descriptor_ui": "D019704", "major_topic": true }, { "descriptor": "Sulfur", "descriptor_ui": "D013455", "major_topic": false } ], "publication": { "conference_name": null, "date": "2022 Oct", "date_precision": "unknown", "issue": "", "normalized_date": null, "pages": "102433", "proceedings_title": null, "publisher": "", "title": "Redox biology", "volume": "56", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Shining a light on SSP4: A comprehensive analysis and biological applications for the detection of sulfane sulfurs.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "INTRODUCTION: Because several articles have reported a prognostic association with the radiologic features of ground-glass opacity, we explored whether the histologic presence of a lepidic component had similar significance. METHODS: We retrospectively evaluated 380 consecutive surgically resected lung adenocarcinomas (ADCs) of pathologic (p)stage IA. The tumors were classified into lepidic-positive and lepidic-negative ADCs. Clinicopathologic characteristics, radiographic ground-glass opacity status, and disease-free survival were compared between lepidic-positive and lepidic-negative ADCs and between part-solid and solid nodules on computed tomography images. RESULTS: Of the 380 cases, 176 (46.3%) were lepidic-positive ADCs. Of the overall patients with pT1, lepidic-positive ADCs were found to have significantly better recurrence-free survival (5 y, 95.4% versus 87.0%, p = 0.005), but this significance was not reproduced in pT1 subcategories (pT1a, pT1b, and pT1c). Furthermore, the presence of the lepidic component was not an independent prognostic factor in the multivariate analysis (hazard ratio = 0.46 [95% confidence interval: 0.19-1.14], p = 0.09). We also analyzed the extent of the lepidic component with 10% incremental valuables. Although we found that a 10% or greater extent of lepidic component made the recurrence-free survival difference the largest, a clear prognostic impact was not obtained with this cutoff point. CONCLUSIONS: Although lepidic-positive ADCs tended to have a favorable outcome, the lepidic component was not a clear independent prognostic factor in pstage I ADC.", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yu", "last_name": "Okubo", "name": null }, { "creator_type": "author", "first_name": "Jumpei", "last_name": "Kashima", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Teishikata", "name": null }, { "creator_type": "author", "first_name": "Yuji", "last_name": "Muraoka", "name": null }, { "creator_type": "author", "first_name": "Masaya", "last_name": "Yotsukura", "name": null }, { "creator_type": "author", "first_name": "Yukihiro", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Kazuo", "last_name": "Nakagawa", "name": null }, { "creator_type": "author", "first_name": "Hirokazu", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Masahiko", "last_name": "Kusumoto", "name": null }, { "creator_type": "author", "first_name": "Shun-Ichi", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.jtho.2021.09.006" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "34634451" } }, "mesh": [ { "descriptor": "Adenocarcinoma", "descriptor_ui": "D000230", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Lung Neoplasms", "descriptor_ui": "D008175", "major_topic": true }, { "descriptor": "Neoplasm Invasiveness", "descriptor_ui": "D009361", "major_topic": false }, { "descriptor": "Neoplasm Staging", "descriptor_ui": "D009367", "major_topic": false }, { "descriptor": "Prognosis", "descriptor_ui": "D011379", "major_topic": false }, { "descriptor": "Retrospective Studies", "descriptor_ui": "D012189", "major_topic": false } ], "publication": { "conference_name": null, "date": "2022 Jan", "date_precision": "unknown", "issue": "1", "normalized_date": null, "pages": "67-75", "proceedings_title": null, "publisher": "", "title": "Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer", "volume": "17", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Prognostic Impact of the Histologic Lepidic Component in Pathologic Stage IA Adenocarcinoma.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease caused by the loss of motor neurons, and development of effective medicines is urgently required. Induced pluripotent stem cell (iPSC)-based drug repurposing identified the Src/c-Abl inhibitor bosutinib, which is approved for the treatment of chronic myelogenous leukemia (CML), as a candidate for the molecular targeted therapy of ALS. METHODS: An open-label, multicentre, dose-escalation phase 1 study using a 3 + 3 design was conducted in 4 hospitals in Japan to evaluate the safety and tolerability of bosutinib in patients with ALS. Furthermore, the exploratory efficacy was evaluated using Revised ALS Functional Rating Scale (ALSFRS-R), predictive biomarkers including plasma neurofilament light chain (NFL) were explored, and single-cell RNA sequencing of iPSC-derived motor neurons was conducted. Patients, whose total ALSFRS-R scores decreased by 1-3 points during the 12-week, received escalating doses starting from 100 mg quaque die (QD) up to 400 mg QD based on dose-limiting toxicity (DLT) occurrence, and all participants who received one dose of the study drug were included in the primary analysis. This trial is registered with ClinicalTrials.gov, NCT04744532, as Induced pluripotent stem cell-based Drug Repurposing for Amyotrophic Lateral Sclerosis Medicine (iDReAM) study. FINDINGS: Between March 29, 2019 and May 7, 2021, 20 patients were enrolled, 13 of whom received bosutinib treatment and 12 were included in the safety and efficacy analyses. No DLTs were observed up to 300 mg QD, but DLTs were observed in 3/3 patients of the 400 mg QD cohort. In all patients receiving 100 mg-400 mg, the prevalent adverse events (AEs) were gastrointestinal AEs in 12 patients (92.3%), liver function related AEs in 7 patients (53.8%), and rash in 3 patients (23.1%). The safety profile was consistent with that known for CML treatment, and ALS-specific AEs were not observed. A subset of patients (5/9 patients) was found to respond well to bosutinib treatment over the 12-week treatment period. It was found that the treatment-responsive patients could be distinguished by their lower levels of plasma NFL. Furthermore, single-cell RNA sequencing of iPSC-derived motor neurons revealed the pathogenesis related molecular signature in patients with ALS showing responsiveness to bosutinib. INTERPRETATION: This is the first trial of a Src/c-Abl inhibitor, bosutinib, for patients with ALS. The safety and tolerability of bosutinib up to 300 mg, not 400 mg, in ALS were described, and responsiveness of patients on motor function was observed. Since this was an open-label trial within a short period with a limited number of patients, further clinical trials will be required. FUNDING: AMED and iPS Cell Research Fund.", "classifications": [ { "id": "Yamamoto", "label": "Group Yamamoto", "parent": "Toyoshima", "type": "group" }, { "id": "Toyoshima", "label": "Team Toyoshima", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Keiko", "last_name": "Imamura", "name": null }, { "creator_type": "author", "first_name": "Yuishin", "last_name": "Izumi", "name": null }, { "creator_type": "author", "first_name": "Makiko", "last_name": "Nagai", "name": null }, { "creator_type": "author", "first_name": "Kazutoshi", "last_name": "Nishiyama", "name": null }, { "creator_type": "author", "first_name": "Yasuhiro", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Ritsuko", "last_name": "Hanajima", "name": null }, { "creator_type": "author", "first_name": "Naohiro", "last_name": "Egawa", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Ayaki", "name": null }, { "creator_type": "author", "first_name": "Ryosuke", "last_name": "Oki", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Fujita", "name": null }, { "creator_type": "author", "first_name": "Ryuji", "last_name": "Uozumi", "name": null }, { "creator_type": "author", "first_name": "Akiko", "last_name": "Morinaga", "name": null }, { "creator_type": "author", "first_name": "Tomoko", "last_name": "Hirohashi", "name": null }, { "creator_type": "author", "first_name": "Yosuke", "last_name": "Fujii", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Harutsugu", "last_name": "Tatebe", "name": null }, { "creator_type": "author", "first_name": "Takahiko", "last_name": "Tokuda", "name": null }, { "creator_type": "author", "first_name": "Naoto", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Morita", "name": null }, { "creator_type": "author", "first_name": "Ryosuke", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Haruhisa", "last_name": "Inoue", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.eclinm.2022.101707" }, "pmcid": { "normalized": "PMC9716331" }, "pmid": { "normalized": "36467452" } }, "mesh": [], "publication": { "conference_name": null, "date": "2022 Nov", "date_precision": "unknown", "issue": "", "normalized_date": null, "pages": "101707", "proceedings_title": null, "publisher": "", "title": "EClinicalMedicine", "volume": "53", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Safety and tolerability of bosutinib in patients with amyotrophic lateral sclerosis (iDReAM study): A multicentre, open-label, dose-escalation phase 1 trial.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Synovial sarcoma is characterized by variable epithelial differentiation and specific SS18-SSX gene fusions. The diagnosis is primarily based on phenotype, but fusion gene detection is increasingly being considered indispensable, with SS18 break-apart fluorescence in situ hybridization (FISH) being favored in many laboratories. However, SS18 FISH assay produces negative or atypical results in a minority of cases, leaving uncertainties in diagnosis and management. Here, we analyzed this challenging subset of SS18 FISH-negative/atypical synovial sarcoma using RNA sequencing and monoclonal antibodies that recognize SS18-SSX and the SSX C-terminus. Among 99 synovial sarcoma cases that were previously subjected to SS18 break-apart FISH, eight cases were reported as negative and three cases were indeterminate, owing to atypical signal patterns. Three of these 11 tumors (two monophasic and one biphasic) harbored novel EWSR1-SSX1 fusions, were negative for SS18-SSX staining, and were positive for SSX C-terminus staining. One monophasic tumor harbored a novel MN1-SSX1 fusion, and showed negative SS18-SSX expression and positive SSX C-terminus staining. Another monophasic tumor carried an SS18L1-SSX1 fusion, and was weakly positive for SS18-SSX, while SMARCB1 expression was reduced. The presence of these novel and/or rare fusions was confirmed using RT-PCR and Sanger sequencing. EWSR1-SSX1 was further validated by EWSR1 FISH assay. The remaining six tumors (five monophasic and one biphasic) showed strong SS18-SSX expression, and RNA sequencing successfully performed in three cases identified canonical SS18-SSX2 fusions. Based on a DNA methylation-based unsupervised clustering, the tumors with EWSR1-SSX1 and SS18L1-SSX1 clustered with synovial sarcoma, while the MN1-SSX1-positive tumor was not co-clustered despite classic histology and immunoprofile. In summary, we discovered novel and rare SSX1 fusions to non-SS18 genes in synovial sarcoma. The expanded genetic landscape carries significant diagnostic implications and advances our understanding of the oncogenic mechanism.", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Akihiko", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Yasuhito", "last_name": "Arai", "name": null }, { "creator_type": "author", "first_name": "Kaishi", "last_name": "Satomi", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Kubo", "name": null }, { "creator_type": "author", "first_name": "Eijitsu", "last_name": "Ryo", "name": null }, { "creator_type": "author", "first_name": "Yuko", "last_name": "Matsushita", "name": null }, { "creator_type": "author", "first_name": "Natsuko", "last_name": "Hama", "name": null }, { "creator_type": "author", "first_name": "Kazuki", "last_name": "Sudo", "name": null }, { "creator_type": "author", "first_name": "Motokiyo", "last_name": "Komiyama", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null }, { "creator_type": "author", "first_name": "Tatsuhiro", "last_name": "Shibata", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Ichikawa", "name": null }, { "creator_type": "author", "first_name": "Koichi", "last_name": "Ichimura", "name": null }, { "creator_type": "author", "first_name": "Akira", "last_name": "Kawai", "name": null }, { "creator_type": "author", "first_name": "Taisuke", "last_name": "Mori", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41379-021-00910-x" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "34504309" } }, "mesh": [ { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "In Situ Hybridization, Fluorescence", "descriptor_ui": "D017404", "major_topic": false }, { "descriptor": "Oncogene Proteins, Fusion", "descriptor_ui": "D015514", "major_topic": false }, { "descriptor": "Proto-Oncogene Proteins", "descriptor_ui": "D011518", "major_topic": false }, { "descriptor": "Repressor Proteins", "descriptor_ui": "D012097", "major_topic": false }, { "descriptor": "Sarcoma, Synovial", "descriptor_ui": "D013584", "major_topic": true } ], "publication": { "conference_name": null, "date": "2022 Feb", "date_precision": "unknown", "issue": "2", "normalized_date": null, "pages": "228-239", "proceedings_title": null, "publisher": "", "title": "Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc", "volume": "35", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Identification of novel SSX1 fusions in synovial sarcoma.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Coronavirus disease 2019 (COVID-19) remains prevalent worldwide since its onset was confirmed in Wuhan, China in 2019. Vaccines against the causative virus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), have shown a preventive effect against the onset and severity of COVID-19, and social and economic activities are gradually recovering. However, the presence of vaccine-resistant variants has been reported, and the development of therapeutic agents for patients with severe COVID-19 and related sequelae remains urgent. Drug repurposing, also called drug repositioning or eco-pharma, is the strategy of using previously approved and safe drugs for a therapeutic indication that is different from their original indication. The risk of severe COVID-19 and mortality increases with advancing age, cardiovascular disease, hypertension, diabetes, and cancer. We have reported three protein-protein interactions that are related to heart failure, and recently identified that one mechanism increases the risk of SARS-CoV-2 infection in mammalian cells. This review outlines the global efforts and outcomes of drug repurposing research for the treatment of severe COVID-19. It also discusses our recent finding of a new protein-protein interaction that is common to COVID-19 aggravation and heart failure.", "classifications": [ { "id": "Nishida", "label": "Group Nishida", "parent": "Nishida", "type": "group" }, { "id": "Nishimura", "label": "Group Nishimura", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yuri", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Kazuhiro", "last_name": "Nishiyama", "name": null }, { "creator_type": "author", "first_name": "Akiyuki", "last_name": "Nishimura", "name": null }, { "creator_type": "author", "first_name": "Takamasa", "last_name": "Noda", "name": null }, { "creator_type": "author", "first_name": "Kaori", "last_name": "Okabe", "name": null }, { "creator_type": "author", "first_name": "Takahiro", "last_name": "Kusakabe", "name": null }, { "creator_type": "author", "first_name": "Yasunari", "last_name": "Kanda", "name": null }, { "creator_type": "author", "first_name": "Motohiro", "last_name": "Nishida", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.jphs.2022.04.007" }, "pmcid": { "normalized": "PMC9040495" }, "pmid": { "normalized": "35641023" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "COVID-19 Drug Treatment", "descriptor_ui": "D000093485", "major_topic": true }, { "descriptor": "Drug Repositioning", "descriptor_ui": "D058492", "major_topic": false }, { "descriptor": "Heart Failure", "descriptor_ui": "D006333", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mammals", "descriptor_ui": "D008322", "major_topic": false }, { "descriptor": "SARS-CoV-2", "descriptor_ui": "D000086402", "major_topic": false } ], "publication": { "conference_name": null, "date": "2022 Jul", "date_precision": "unknown", "issue": "3", "normalized_date": null, "pages": "108-114", "proceedings_title": null, "publisher": "", "title": "Journal of pharmacological sciences", "volume": "149", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Drug repurposing for the treatment of COVID-19.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Recent technological advances in high-resolution imaging and artificial modulation of genetic functions at different times and regions have enabled direct observations of the formation and elimination of abnormal cell populations. A recent trend in cell competition research is the incorporation of cell mechanics. In different tissues and species, abnormal cells developing in epithelial tissues are mechanically eliminated by cell contraction via actomyosin accumulation at the interface between normal and abnormal cells. This mechanical cell elimination process has attracted attention as a potential universal defense mechanism. Here, we theoretically examined the conditions for mechanical elimination of growing abnormal cell populations. Simulations and mathematical analyses using a vertex dynamics model revealed two types of critical cell density associated with mechanical elimination of abnormal cell clusters. One is a subtype of homeostatic density, in which the frequencies of spontaneous mechanical cell elimination and proliferation are balanced, even if no explicit dependence of proliferation or apoptosis on the cell density is assumed. This density is related to the mechanical stability of a single cell. The other is density related to mechanical stability as a cell population under external pressure. Both density types are determined by tissue mechanical properties. In solid tissues, the former type is reached first as the intensity of interfacial contraction increases, and it functions as a critical density. On the other hand, the latter type becomes critical when tissues are highly fluid. The derived analytical solution explicitly reveals the dependence of critical contractile force and density on different parameters. We also found a negative correlation between the proliferation rate of abnormal cells and the likelihood of the abnormal cell population expanding by escaping elimination. This is counterintuitive because in the context of cell competition, fast-growing cell populations generally win. These findings provide new insight into, and interpretation of, the results from experimental studies.", "classifications": [ { "id": "Morishita", "label": "Group Morishita", "parent": "Morishita", "type": "group" }, { "id": "Morishita", "label": "Team Morishita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Sang-Woo", "last_name": "Lee", "name": null }, { "creator_type": "author", "first_name": "Yoshihiro", "last_name": "Morishita", "name": null } ], "identifiers": { "doi": { "normalized": "10.1371/journal.pcbi.1010178" }, "pmcid": { "normalized": "PMC9232172" }, "pmid": { "normalized": "35696420" } }, "mesh": [ { "descriptor": "Actin Cytoskeleton", "descriptor_ui": "D008841", "major_topic": true }, { "descriptor": "Apoptosis", "descriptor_ui": "D017209", "major_topic": true }, { "descriptor": "Cell Count", "descriptor_ui": "D002452", "major_topic": false }, { "descriptor": "Epithelium", "descriptor_ui": "D004848", "major_topic": false }, { "descriptor": "Homeostasis", "descriptor_ui": "D006706", "major_topic": false } ], "publication": { "conference_name": null, "date": "2022 Jun", "date_precision": "unknown", "issue": "6", "normalized_date": null, "pages": "e1010178", "proceedings_title": null, "publisher": "", "title": "PLoS computational biology", "volume": "18", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Two types of critical cell density for mechanical elimination of abnormal cell clusters from epithelial tissue.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Human pluripotent stem cell-derived muscle progenitor cells (hiPSC-MuPCs) resemble fetal-stage muscle progenitor cells and possess in vivo regeneration capacity. However, the heterogeneity of hiPSC-MuPCs is unknown, which could impact the regenerative potential of these cells. Here, we established an hiPSC-MuPC atlas by performing single-cell RNA sequencing of hiPSC-MuPC cultures. Bioinformatic analysis revealed four cell clusters for hiPSC-MuPCs: myocytes, committed, cycling, and noncycling progenitors Using FGFR4 as a marker for noncycling progenitors and cycling cells and CD36 as a marker for committed and myocyte cells, we found that FGFR4+ cells possess a higher regenerative capacity than CD36(+) cells. We also identified the family of E2F transcription factors are key regulators of hiPSC-MuPC proliferation. Our study provides insights on the purification of hiPSC-MuPCs with higher regenerative potential and increases the understanding of the transcriptional regulation of hiPSC-MuPCs.", "classifications": [ { "id": "Yamamoto", "label": "Group Yamamoto", "parent": "Toyoshima", "type": "group" }, { "id": "Toyoshima", "label": "Team Toyoshima", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Minas", "last_name": "Nalbandian", "name": null }, { "creator_type": "author", "first_name": "Mingming", "last_name": "Zhao", "name": null }, { "creator_type": "author", "first_name": "Hiroki", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Jonouchi", "name": null }, { "creator_type": "author", "first_name": "May", "last_name": "Nakajima-Koyama", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Hidetoshi", "last_name": "Sakurai", "name": null } ], "identifiers": { "doi": { "normalized": "10.26508/lsa.202101312" }, "pmcid": { "normalized": "PMC9034463" }, "pmid": { "normalized": "35459735" } }, "mesh": [ { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Cell Proliferation", "descriptor_ui": "D049109", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Induced Pluripotent Stem Cells", "descriptor_ui": "D057026", "major_topic": true }, { "descriptor": "Muscles", "descriptor_ui": "D009132", "major_topic": false }, { "descriptor": "RNA-Seq", "descriptor_ui": "D000081246", "major_topic": false } ], "publication": { "conference_name": null, "date": "2022 Aug", "date_precision": "unknown", "issue": "8", "normalized_date": null, "pages": "e202101312", "proceedings_title": null, "publisher": "", "title": "Life science alliance", "volume": "5", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Single-cell RNA-seq reveals heterogeneity in hiPSC-derived muscle progenitors and E2F family as a key regulator of proliferation.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "", "classifications": [ { "id": "Nikaido", "label": "Group Nikaido", "parent": "Fujiwara", "type": "group" }, { "id": "Shintaku", "label": "Group Shintaku", "parent": "Shintaku", "type": "group" }, { "id": "Fujiwara", "label": "Team Fujiwara", "type": "team" }, { "id": "Shintaku", "label": "Team Shintaku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Maik", "last_name": "Herbig", "name": null }, { "creator_type": "author", "first_name": "Akihiro", "last_name": "Isozaki", "name": null }, { "creator_type": "author", "first_name": "Dino", "last_name": "Di Carlo", "name": null }, { "creator_type": "author", "first_name": "Jochen", "last_name": "Guck", "name": null }, { "creator_type": "author", "first_name": "Nao", "last_name": "Nitta", "name": null }, { "creator_type": "author", "first_name": "Robert", "last_name": "Damoiseaux", "name": null }, { "creator_type": "author", "first_name": "Shogo", "last_name": "Kamikawaji", "name": null }, { "creator_type": "author", "first_name": "Eigo", "last_name": "Suyama", "name": null }, { "creator_type": "author", "first_name": "Hirofumi", "last_name": "Shintaku", "name": null }, { "creator_type": "author", "first_name": "Angela Ruohao", "last_name": "Wu", "name": null }, { "creator_type": "author", "first_name": "Itoshi", "last_name": "Nikaido", "name": null }, { "creator_type": "author", "first_name": "Keisuke", "last_name": "Goda", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41592-022-01483-6" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "35508736" } }, "mesh": [ { "descriptor": "Biomedical Research", "descriptor_ui": "D035843", "major_topic": true } ], "publication": { "conference_name": null, "date": "2022 Jun", "date_precision": "unknown", "issue": "6", "normalized_date": null, "pages": "633-634", "proceedings_title": null, "publisher": "", "title": "Nature methods", "volume": "19", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Best practices for reporting throughput in biomedical research.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The current World Health Organization classification of diffuse astrocytic and oligodendroglial tumors requires the examination of isocitrate dehydrogenase 1 (IDH1) or IDH2 mutations. Conventional analysis tools, including Sanger DNA sequencing or pyrosequencing, fail in detecting these variants of low frequency owing to their limited sensitivity. Digital polymerase chain reaction (dPCR) is a recently developed, highly sensitive, and precise quantitative rare variant assay. This study aimed to establish a robust limit of quantitation of the dPCR assay to detect a small fraction of IDH1 R132H mutation. The dPCR assays with serially diluted IDH1 R132H constructs detected 0.05% or more of mutant IDH1 R132H in samples containing mutant DNA. The measured target/total value of the experiments was proportional to the dilution factors and was almost equal to the actual frequencies of the mutant alleles. Based on the average target/total values, together with a twofold standard deviation of the normal DNA, a limit of quantitation of 0.25% was set to secure a safe margin to judge the mutation status of the IDH1 R132H dPCR assay. In clinical settings, detecting IDH1 R132H using dPCR assays can validate ambiguous immunohistochemistry results even when conventional DNA sequencing cannot detect the mutation and assure diagnostic quality.", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Kaishi", "last_name": "Satomi", "name": null }, { "creator_type": "author", "first_name": "Akihiko", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Yuko", "last_name": "Matsushita", "name": null }, { "creator_type": "author", "first_name": "Hirokazu", "last_name": "Sugino", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Fujimoto", "name": null }, { "creator_type": "author", "first_name": "Mai", "last_name": "Honda-Kitahara", "name": null }, { "creator_type": "author", "first_name": "Masamichi", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Ohno", "name": null }, { "creator_type": "author", "first_name": "Yasuji", "last_name": "Miyakita", "name": null }, { "creator_type": "author", "first_name": "Yoshitaka", "last_name": "Narita", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null }, { "creator_type": "author", "first_name": "Junji", "last_name": "Shibahara", "name": null }, { "creator_type": "author", "first_name": "Koichi", "last_name": "Ichimura", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/s10014-022-00442-5" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "35902443" } }, "mesh": [ { "descriptor": "Alleles", "descriptor_ui": "D000483", "major_topic": false }, { "descriptor": "Brain Neoplasms", "descriptor_ui": "D001932", "major_topic": true }, { "descriptor": "Glioma", "descriptor_ui": "D005910", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Isocitrate Dehydrogenase", "descriptor_ui": "D007521", "major_topic": false }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": false }, { "descriptor": "Polymerase Chain Reaction", "descriptor_ui": "D016133", "major_topic": false } ], "publication": { "conference_name": null, "date": "2022 Oct", "date_precision": "unknown", "issue": "4", "normalized_date": null, "pages": "210-217", "proceedings_title": null, "publisher": "", "title": "Brain tumor pathology", "volume": "39", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Clinical application of a highly sensitive digital PCR assay to detect a small fraction of IDH1 R132H-mutant alleles in diffuse gliomas.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "beta cells have a limited capacity for regeneration, which predisposes towards diabetes. Here, we show that, of the MYC family members, Mycl plays a key role in proliferation of pancreatic endocrine cells. Genetic ablation of Mycl causes a reduction in the proliferation of pancreatic endocrine cells in neonatal mice. By contrast, the expression of Mycl in adult mice stimulates the proliferation of beta and alpha cells, and the cells persist after withdrawal of Mycl expression. A subset of the expanded alpha cells give rise to insulin-producing cells after this withdrawal. Transient Mycl expression in vivo is sufficient to normalize the hyperglycaemia of diabetic mice. In vitro expression of Mycl similarly provokes active replication in islet cells, even in those from aged mice. Finally, we show that MYCL stimulates the division of human adult cadaveric islet cells. Our results demonstrate that the induction of Mycl alone expands the functional beta-cell population, which may provide a regenerative strategy for beta cells.", "classifications": [ { "id": "Yamamoto", "label": "Group Yamamoto", "parent": "Toyoshima", "type": "group" }, { "id": "Toyoshima", "label": "Team Toyoshima", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Michitada", "last_name": "Hirano", "name": null }, { "creator_type": "author", "first_name": "Yusei", "last_name": "So", "name": null }, { "creator_type": "author", "first_name": "Shin", "last_name": "Tsunekawa", "name": null }, { "creator_type": "author", "first_name": "Mio", "last_name": "Kabata", "name": null }, { "creator_type": "author", "first_name": "Sho", "last_name": "Ohta", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Sagara", "name": null }, { "creator_type": "author", "first_name": "Nao", "last_name": "Sankoda", "name": null }, { "creator_type": "author", "first_name": "Jumpei", "last_name": "Taguchi", "name": null }, { "creator_type": "author", "first_name": "Yosuke", "last_name": "Yamada", "name": null }, { "creator_type": "author", "first_name": "Tomoyo", "last_name": "Ukai", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Jiro", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Manabu", "last_name": "Ozawa", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Yasuhiro", "last_name": "Yamada", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s42255-022-00530-y" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "35145326" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Diabetes Mellitus, Experimental", "descriptor_ui": "D003921", "major_topic": true }, { "descriptor": "Glucagon-Secreting Cells", "descriptor_ui": "D050416", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Insulin", "descriptor_ui": "D007328", "major_topic": false }, { "descriptor": "Insulin-Secreting Cells", "descriptor_ui": "D050417", "major_topic": true }, { "descriptor": "Islets of Langerhans", "descriptor_ui": "D007515", "major_topic": true }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Pancreatic Hormones", "descriptor_ui": "D010187", "major_topic": false } ], "publication": { "conference_name": null, "date": "2022 Feb", "date_precision": "unknown", "issue": "2", "normalized_date": null, "pages": "254-268", "proceedings_title": null, "publisher": "", "title": "Nature metabolism", "volume": "4", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "MYCL-mediated reprogramming expands pancreatic insulin-producing cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "PURPOSE: To investigate the clinical characteristics and causative fungi in patients with fungal keratitis in Japan, and to determine factors related to the prognosis. STUDY DESIGN: Multicenter prospective observational study. METHODS: Eligible patients were enrolled from November 2011 to October 2013 at the 1st stage and from April 2015 to March 2016 at the 2nd stage. The corneal foci were scraped, and the scrapings were cultured in potato dextrose agar. The isolated fungi were identified by gene analyses. Data were collected from the clinical records and statistically analyzed by Cox and logistic regression analyses. RESULTS: Ninety-four fungal strains were isolated from 93 cases, including 42 yeast-like fungi and 52 filamentous fungi. The fungi affected the deep layers of the cornea in 23 cases (24.7%) and the peripheral cornea in 29 cases (31.2%). The incidences of lid swelling/redness, ciliary injection, anterior chamber cells/flare, anterior chamber fibrin, and hyphate ulcer in cases of filamentous fungi were significantly higher than in yeast-like fungi. No history of topical steroids, absence of a main lesion in the peripheral cornea, and best-corrected visual acuity (BCVA) of more than 0.04 at the first visit were related to a shorter healing time. No history of ocular surgery, absence of lesion at one-third deep stromal layer and BCVA of more than 0.04 at the first visit were correlated with BCVA at 3 months after the initial examination. CONCLUSION: Fungal keratitis is caused by various species of fungi and can become refractory due to poor prognosis factors.", "classifications": [ { "id": "Suzuki", "label": "Group Suzuki", "parent": "Takekawa", "type": "group" }, { "id": "Takekawa", "label": "Team Takekawa", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yoshitsugu", "last_name": "Inoue", "name": null }, { "creator_type": "author", "first_name": "Yuichi", "last_name": "Ohashi", "name": null }, { "creator_type": "author", "first_name": "Yoshikazu", "last_name": "Shimomura", "name": null }, { "creator_type": "author", "first_name": "Chie", "last_name": "Sotozono", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Hatano", "name": null }, { "creator_type": "author", "first_name": "Masahiko", "last_name": "Fukuda", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Eguchi", "name": null }, { "creator_type": "author", "first_name": "Kaoru", "last_name": "Araki-Sasaki", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Saichi", "last_name": "Hoshi", "name": null }, { "creator_type": "author", "first_name": "Seishi", "last_name": "Asari", "name": null }, { "creator_type": "author", "first_name": "Atsuko", "last_name": "Sunada", "name": null }, { "creator_type": "author", "first_name": "Keigo", "last_name": "Kimura", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Yaguchi", "name": null }, { "creator_type": "author", "first_name": "Koichi", "last_name": "Makimura", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/s10384-022-00904-5" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "35348982" } }, "mesh": [ { "descriptor": "Antifungal Agents", "descriptor_ui": "D000935", "major_topic": false }, { "descriptor": "Corneal Ulcer", "descriptor_ui": "D003320", "major_topic": true }, { "descriptor": "Eye Infections, Fungal", "descriptor_ui": "D015821", "major_topic": true }, { "descriptor": "Fungi", "descriptor_ui": "D005658", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Japan", "descriptor_ui": "D007564", "major_topic": false }, { "descriptor": "Keratitis", "descriptor_ui": "D007634", "major_topic": true }, { "descriptor": "Saccharomyces cerevisiae", "descriptor_ui": "D012441", "major_topic": false } ], "publication": { "conference_name": null, "date": "2022 May", "date_precision": "unknown", "issue": "3", "normalized_date": null, "pages": "227-239", "proceedings_title": null, "publisher": "", "title": "Japanese journal of ophthalmology", "volume": "66", "year": 2022 }, "ssbd": { "database": [], "repository": [] }, "title": "Multicenter prospective observational study of fungal keratitis in Japan: analyses of culture-positive cases.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "OBJECTIVES: To evaluate the effect of emphysema on tumor diameter measured on preoperative computed tomography (CT) images versus pathological specimens. MATERIALS AND METHODS: We investigated patients who underwent primary lung cancer surgery: 55 patients (57 tumors) with severe emphysema and 57 patients (57 tumors) without emphysema. The tumor diameters measured in the postoperative pathological specimens were compared with those measured on the axial CT images and on multiplanar reconstruction (MPR) CT images by two independent radiologists; a subgroup analysis according to tumor size was also performed. A paired or unpaired t test was performed, depending on the tested subjects. RESULTS: In the emphysema group, the mean axial CT diameter was significantly smaller than the mean pathological diameter (p = 0.025/0.001 for reader 1/2), whereas in the non-emphysema group, the mean axial CT diameter was not significantly different from the pathological one for both readers. The difference between CT axial diameter and pathological diameter (= CT diameter - pathological diameter) was significantly smaller (i.e., had a stronger tendency toward underestimation on radiological measurements) in the emphysema group compared with the non-emphysema group (p = 0.014/0.008 for reader 1/2), and the difference was significantly smaller in tumors sized > 30 mm than tumors sized /=100 kb) with differential H3K9me3 enrichment, many of which are lamina-associated domains (LADs) in somatic but not in embryonic stem cells. A majority of these epigenomic heterogeneities are independent of genetic variations. We identify an X chromosome state with chromosome-wide H3K9me3 that stably prevents X chromosome erosion. Importantly, the germline potential of female hiPSCs correlates with X chromosome inactivation. We propose that inherent genomic properties, including CpG density, transposons, and LADs, engender epigenomic heterogeneity in hiPSCs.", "classifications": [ { "id": "Yamamoto", "label": "Group Yamamoto", "parent": "Toyoshima", "type": "group" }, { "id": "Toyoshima", "label": "Team Toyoshima", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Shihori", "last_name": "Yokobayashi", "name": null }, { "creator_type": "author", "first_name": "Yukihiro", "last_name": "Yabuta", "name": null }, { "creator_type": "author", "first_name": "Masato", "last_name": "Nakagawa", "name": null }, { "creator_type": "author", "first_name": "Keisuke", "last_name": "Okita", "name": null }, { "creator_type": "author", "first_name": "Bo", "last_name": "Hu", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Murase", "name": null }, { "creator_type": "author", "first_name": "Tomonori", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Guillaume", "last_name": "Bourque", "name": null }, { "creator_type": "author", "first_name": "Jacek", "last_name": "Majewski", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Mitinori", "last_name": "Saitou", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.celrep.2021.109909" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "34731633" } }, "mesh": [ { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "Chromatin Assembly and Disassembly", "descriptor_ui": "D042002", "major_topic": false }, { "descriptor": "Chromosomes, Human, X", "descriptor_ui": "D041321", "major_topic": true }, { "descriptor": "CpG Islands", "descriptor_ui": "D018899", "major_topic": false }, { "descriptor": "DNA Transposable Elements", "descriptor_ui": "D004251", "major_topic": false }, { "descriptor": "Epigenesis, Genetic", "descriptor_ui": "D044127", "major_topic": true }, { "descriptor": "Epigenome", "descriptor_ui": "D000081122", "major_topic": true }, { "descriptor": "Epigenomics", "descriptor_ui": "D057890", "major_topic": false }, { "descriptor": "Evolution, Molecular", "descriptor_ui": "D019143", "major_topic": false }, { "descriptor": "Genetic Heterogeneity", "descriptor_ui": "D018740", "major_topic": true }, { "descriptor": "Histones", "descriptor_ui": "D006657", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Induced Pluripotent Stem Cells", "descriptor_ui": "D057026", "major_topic": false }, { "descriptor": "Methylation", "descriptor_ui": "D008745", "major_topic": false }, { "descriptor": "Nuclear Lamina", "descriptor_ui": "D034881", "major_topic": false }, { "descriptor": "Protein Processing, Post-Translational", "descriptor_ui": "D011499", "major_topic": false }, { "descriptor": "RNA, Long Noncoding", "descriptor_ui": "D062085", "major_topic": false }, { "descriptor": "X Chromosome Inactivation", "descriptor_ui": "D049951", "major_topic": true } ], "publication": { "conference_name": null, "date": "2021 Nov 2", "date_precision": "day", "issue": "5", "normalized_date": "2021-11-02", "pages": "109909", "proceedings_title": null, "publisher": "", "title": "Cell reports", "volume": "37", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Inherent genomic properties underlie the epigenomic heterogeneity of human induced pluripotent stem cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yuuki", "last_name": "Nishimura", "name": null }, { "creator_type": "author", "first_name": "Eijitsu", "last_name": "Ryo", "name": null }, { "creator_type": "author", "first_name": "Naoya", "last_name": "Yamazaki", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null }, { "creator_type": "author", "first_name": "Taisuke", "last_name": "Mori", "name": null } ], "identifiers": { "doi": { "normalized": "10.1097/pas.0000000000001801" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "34482332" } }, "mesh": [ { "descriptor": "Bromodomain Containing Proteins", "descriptor_ui": "D000092468", "major_topic": false }, { "descriptor": "Carcinoma", "descriptor_ui": "D002277", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Transcription Factors", "descriptor_ui": "D014157", "major_topic": true } ], "publication": { "conference_name": null, "date": "2021 Nov 1", "date_precision": "day", "issue": "11", "normalized_date": "2021-11-01", "pages": "1582-1584", "proceedings_title": null, "publisher": "", "title": "The American journal of surgical pathology", "volume": "45", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Cutaneous Primary NUT Carcinoma With BRD3-NUTM1 Fusion.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Sulfides and persulfides/polysulfides (R-Sn-R', n > 2; R-Sn-H, n > 1) are endogenously produced metabolites that are abundant in mammalian and human cells and tissues. The most typical persulfides that are widely distributed among different organisms include various reactive persulfides-low-molecular-weight thiol compounds such as cysteine hydropersulfide, glutathione hydropersulfide, and glutathione trisulfide as well as protein-bound thiols. These species are generally more redox-active than are other simple thiols and disulfides. Although hydrogen sulfide (H2S) has been suggested for years to be a small signaling molecule, it is intimately linked biochemically to persulfides and may actually be more relevant as a marker of functionally active persulfides. Reactive persulfides can act as powerful antioxidants and redox signaling species and are involved in energy metabolism. Recent evidence revealed that cysteinyl-tRNA synthetases (CARSs) act as the principal cysteine persulfide synthases in mammals and contribute significantly to endogenous persulfide/polysulfide production, in addition to being associated with a battery of enzymes including cystathionine beta-synthase, cystathionine gamma-lyase, and 3-mercaptopyruvate sulfurtransferase, which have been described as H2S-producing enzymes. The reactive sulfur metabolites including persulfides/polysulfides derived from CARS2, a mitochondrial isoform of CARS, also mediate not only mitochondrial biogenesis and bioenergetics but also anti-inflammatory and immunomodulatory functions. The physiological roles of persulfides, their biosynthetic pathways, and their pathophysiology in various diseases are not fully understood, however. Developing basic and high precision techniques and methods for the detection, characterization, and quantitation of sulfides and persulfides is therefore of great importance so as to thoroughly understand and clarify the exact functions and roles of these species in cells and in vivo.", "classifications": [ { "id": "JPMJCR2024", "label": "JPMJCR2024", "researcher": "Motohiro Nishida", "type": "grant" }, { "id": "Akaike", "label": "Group Akaike", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Group Nishida", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Tsuyoshi", "last_name": "Takata", "name": null }, { "creator_type": "author", "first_name": "Minkyung", "last_name": "Jung", "name": null }, { "creator_type": "author", "first_name": "Tetsuro", "last_name": "Matsunaga", "name": null }, { "creator_type": "author", "first_name": "Tomoaki", "last_name": "Ida", "name": null }, { "creator_type": "author", "first_name": "Masanobu", "last_name": "Morita", "name": null }, { "creator_type": "author", "first_name": "Hozumi", "last_name": "Motohashi", "name": null }, { "creator_type": "author", "first_name": "Xinggui", "last_name": "Shen", "name": null }, { "creator_type": "author", "first_name": "Christopher G.", "last_name": "Kevil", "name": null }, { "creator_type": "author", "first_name": "Jon M.", "last_name": "Fukuto", "name": null }, { "creator_type": "author", "first_name": "Takaaki", "last_name": "Akaike", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.niox.2021.09.002" }, "pmcid": { "normalized": "PMC8486624" }, "pmid": { "normalized": "34534626" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "Chemistry Techniques, Analytical", "descriptor_ui": "D002623", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Hydrogen Sulfide", "descriptor_ui": "D006862", "major_topic": false }, { "descriptor": "Protein Processing, Post-Translational", "descriptor_ui": "D011499", "major_topic": false }, { "descriptor": "Proteins", "descriptor_ui": "D011506", "major_topic": false }, { "descriptor": "Proteomics", "descriptor_ui": "D040901", "major_topic": false }, { "descriptor": "Sulfides", "descriptor_ui": "D013440", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Nov 1", "date_precision": "day", "issue": "", "normalized_date": "2021-11-01", "pages": "47-64", "proceedings_title": null, "publisher": "", "title": "Nitric oxide : biology and chemistry", "volume": "116", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Methods in sulfide and persulfide research.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yasuhisa", "last_name": "Hasegawa", "name": null }, { "creator_type": "author", "first_name": "Kiyoaki", "last_name": "Tsukahara", "name": null }, { "creator_type": "author", "first_name": "Seiichi", "last_name": "Yoshimoto", "name": null }, { "creator_type": "author", "first_name": "Kouki", "last_name": "Miura", "name": null }, { "creator_type": "author", "first_name": "Junkichi", "last_name": "Yokoyama", "name": null }, { "creator_type": "author", "first_name": "Shigeru", "last_name": "Hirano", "name": null }, { "creator_type": "author", "first_name": "Hirokazu", "last_name": "Uemura", "name": null }, { "creator_type": "author", "first_name": "Masashi", "last_name": "Sugasawa", "name": null }, { "creator_type": "author", "first_name": "Tomokazu", "last_name": "Yoshizaki", "name": null }, { "creator_type": "author", "first_name": "Akihiro", "last_name": "Homma", "name": null }, { "creator_type": "author", "first_name": "Kazuaki", "last_name": "Chikamatsu", "name": null }, { "creator_type": "author", "first_name": "Mikio", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Akihiro", "last_name": "Shiotani", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Matsuzuka", "name": null }, { "creator_type": "author", "first_name": "Naoyuki", "last_name": "Kohno", "name": null }, { "creator_type": "author", "first_name": "Masakazu", "last_name": "Miyazaki", "name": null }, { "creator_type": "author", "first_name": "Isao", "last_name": "Oze", "name": null }, { "creator_type": "author", "first_name": "Keitaro", "last_name": "Matsuo", "name": null }, { "creator_type": "author", "first_name": "Shigeru", "last_name": "Kosuda", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null } ], "identifiers": { "doi": { "normalized": "10.1200/jco.21.01554" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "34506232" } }, "mesh": [], "publication": { "conference_name": null, "date": "2021 Nov 1", "date_precision": "day", "issue": "31", "normalized_date": "2021-11-01", "pages": "3518-3519", "proceedings_title": null, "publisher": "", "title": "Journal of clinical oncology : official journal of the American Society of Clinical Oncology", "volume": "39", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Reply to P. Kaul et al.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Macropinocytosis refers to the non-specific uptake of extracellular fluid, which plays ubiquitous roles in cell growth, immune surveillance, and virus entry. Despite its widespread occurrence, it remains unclear how its initial cup-shaped plasma membrane extensions form without any external solid support, as opposed to the process of particle uptake during phagocytosis. Here, by developing a computational framework that describes the coupling between the bistable reaction-diffusion processes of active signaling patches and membrane deformation, we demonstrated that the protrusive force localized to the edge of the patches can give rise to a self-enclosing cup structure, without further assumptions of local bending or contraction. Efficient uptake requires a balance among the patch size, magnitude of protrusive force, and cortical tension. Furthermore, our model exhibits cyclic cup formation, coexistence of multiple cups, and cup-splitting, indicating that these complex morphologies self-organize via a common mutually-dependent process of reaction-diffusion and membrane deformation.", "classifications": [ { "id": "JPMJCR1923", "label": "JPMJCR1923", "researcher": "Satoshi Sawai", "type": "grant" }, { "id": "Sawai", "label": "Group Sawai", "parent": "Sawai", "type": "group" }, { "id": "Sawai", "label": "Team Sawai", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Nen", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Sawai", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.isci.2021.103087" }, "pmcid": { "normalized": "PMC8560551" }, "pmid": { "normalized": "34755081" } }, "mesh": [], "publication": { "conference_name": null, "date": "2021 Oct 22", "date_precision": "day", "issue": "10", "normalized_date": "2021-10-22", "pages": "103087", "proceedings_title": null, "publisher": "", "title": "iScience", "volume": "24", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Three-dimensional morphodynamic simulations of macropinocytic cups.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Monocarboxylates, such as lactate and pyruvate, are precursors for biosynthetic pathways, including those for glucose, lipids, and amino acids via the tricarboxylic acid (TCA) cycle and adjacent metabolic networks. The transportation of monocarboxylates across the cellular membrane is performed primarily by monocarboxylate transporters (MCTs), the membrane localization and stabilization of which are facilitated by the transmembrane protein basigin (BSG). Here, we demonstrate that the MCT/BSG axis sits at a crucial intersection of cellular metabolism. Abolishment of MCT1 in the plasma membrane was achieved by Bsg depletion, which led to gluconeogenesis impairment via preventing the influx of lactate and pyruvate into the cell, consequently suppressing the TCA cycle. This net anaplerosis suppression was compensated in part by the increased utilization of glycogenic amino acids (e.g., alanine and glutamine) into the TCA cycle and by activated ketogenesis through fatty acid β-oxidation. Complementary to these observations, hyperglycemia and hepatic steatosis induced by a high-fat diet were ameliorated in Bsg-deficient mice. Furthermore, Bsg deficiency significantly improved insulin resistance induced by a high-fat diet. Taken together, the plasma membrane–selective modulation of lactate and pyruvate transport through BSG inhibition could potentiate metabolic flexibility to treat metabolic diseases.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Akihiro", "last_name": "Ryuge", "name": null }, { "creator_type": "author", "first_name": "Tomoki", "last_name": "Kosugi", "name": null }, { "creator_type": "author", "first_name": "Kayaho", "last_name": "Maeda", "name": null }, { "creator_type": "author", "first_name": "Ryoichi", "last_name": "Banno", "name": null }, { "creator_type": "author", "first_name": "Yang", "last_name": "Gou", "name": null }, { "creator_type": "author", "first_name": "Kei", "last_name": "Zaitsu", "name": null }, { "creator_type": "author", "first_name": "Takanori", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Yuka", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Akiyoshi", "last_name": "Hirayama", "name": null }, { "creator_type": "author", "first_name": "Shoma", "last_name": "Tsubota", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Honda", "name": null }, { "creator_type": "author", "first_name": "Kazuki", "last_name": "Nakajima", "name": null }, { "creator_type": "author", "first_name": "Tomoya", "last_name": "Ozaki", "name": null }, { "creator_type": "author", "first_name": "Kunio", "last_name": "Kondoh", "name": null }, { "creator_type": "author", "first_name": "Kazuo", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Noritoshi", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Takuji", "last_name": "Ishimoto", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Takahiko", "last_name": "Nakagawa", "name": null }, { "creator_type": "author", "first_name": "Teruhiko", "last_name": "Koike", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Arima", "name": null }, { "creator_type": "author", "first_name": "Yukio", "last_name": "Yuzawa", "name": null }, { "creator_type": "author", "first_name": "Yasuhiko", "last_name": "Minokoshi", "name": null }, { "creator_type": "author", "first_name": "Shoichi", "last_name": "Maruyama", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Kadomatsu", "name": null } ], "identifiers": { "doi": { "normalized": "10.1172/jci.insight.142464" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "34676828" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Basigin", "descriptor_ui": "D051926", "major_topic": false }, { "descriptor": "Fatty Liver", "descriptor_ui": "D005234", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Insulin Resistance", "descriptor_ui": "D007333", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021-10-22", "date_precision": "day", "issue": "20", "normalized_date": "2021-10-22", "pages": "", "proceedings_title": null, "publisher": "", "title": "JCI Insight", "volume": "6", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Basigin deficiency prevents anaplerosis and ameliorates insulin resistance and hepatosteatosis.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "In recent years, the diversity of cancer cells in tumor tissues as a result of intratumor heterogeneity has attracted attention. In particular, the development of single-cell analysis technology has made a significant contribution to the field; technologies that are centered on single-cell RNA sequencing (scRNA-seq) have been reported to analyze cancer constituent cells, identify cell groups responsible for therapeutic resistance, and analyze gene signatures of resistant cell groups. However, although single-cell analysis is a powerful tool, various issues have been reported, including batch effects and transcriptional noise due to gene expression variation and mRNA degradation. To overcome these issues, machine learning techniques are currently being introduced for single-cell analysis, and promising results are being reported. In addition, machine learning has also been used in various ways for single-cell analysis, such as single-cell assay of transposase accessible chromatin sequencing (ATAC-seq), chromatin immunoprecipitation sequencing (ChIP-seq) analysis, and multi-omics analysis; thus, it contributes to a deeper understanding of the characteristics of human diseases, especially cancer, and supports clinical applications. In this review, we present a comprehensive introduction to the implementation of machine learning techniques in medical research for single-cell analysis, and discuss their usefulness and future potential.", "classifications": [ { "id": "Hamamoto", "label": "Group Hamamoto", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Group Okamoto", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Ken", "last_name": "Asada", "name": null }, { "creator_type": "author", "first_name": "Ken", "last_name": "Takasawa", "name": null }, { "creator_type": "author", "first_name": "Hidenori", "last_name": "Machino", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Norio", "last_name": "Shinkai", "name": null }, { "creator_type": "author", "first_name": "Amina", "last_name": "Bolatkan", "name": null }, { "creator_type": "author", "first_name": "Kazuma", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Masaaki", "last_name": "Komatsu", "name": null }, { "creator_type": "author", "first_name": "Syuzo", "last_name": "Kaneko", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Okamoto", "name": null }, { "creator_type": "author", "first_name": "Ryuji", "last_name": "Hamamoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.3390/biomedicines9111513" }, "pmcid": { "normalized": "PMC8614827" }, "pmid": { "normalized": "34829742" } }, "mesh": [], "publication": { "conference_name": null, "date": "2021 Oct 21", "date_precision": "day", "issue": "11", "normalized_date": "2021-10-21", "pages": "1513", "proceedings_title": null, "publisher": "", "title": "Biomedicines", "volume": "9", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Single-Cell Analysis Using Machine Learning Techniques and Its Application to Medical Research.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Devising synthetic strategies to construct a covalent bond is a common research topic among synthetic chemists. A key driver of success is the high tunability of the conditions, including catalysts, reagents, solvents, and reaction temperature. Such flexibility of synthetic operations has allowed for the rapid exploration of a myriad of artificial synthetic transformations in recent decades. However, if we turn our attention to chemical reactions controlled in living cells, the situation is quite different; the number of hit substrates for the reaction-type is relatively small, while the crowded environment is chemically complex and inflexible to control.A specific objective of this Account is to introduce our chemical methylome analysis as an example of bridging the gap between chemistry and biology. Protein methylation, catalyzed by protein methyltransferases (MTases) using S-adenosyl-l-methionine (SAM or AdoMet) as a methyl donor, is a simple but important post-translational covalent modification. We aim to efficiently identify MTase substrates and methylation sites using activity-based protein profiling (ABPP) with propargylic Se-adenosyl-l-selenomethionine (ProSeAM, also called SeAdoYn). Specifically, we draw heavily from quantitative proteomics that yields information about the differences between two samples utilizing LC-MS/MS analysis. By exploiting the use of ProSeAM, we have prepared the requisite two samples for quantitative methylome analysis. The structural difference between ProSeAM and the parent SAM is so small that the quantity of modification of the protein substrate with this artificial cofactor reflects, to a large extent, levels of activity of the MTase of interest with SAM. First, we identified that the addition of exogenous recombinant MTase (methylation accel), a natural catalyst, enhances the generation of the corresponding propargylated product even in the cell lysate. Then, we applied the principle to isotope label-free quantification with HEK293T cell lysates. By comparing the intensity of LC-MS/MS signals in the absence and presence of the MTase, we have successfully correlated the MTase substrates. We have currently applied the concept to the stable isotope label-based quantification, SILAC (stable isotope labeling by amino acids in cell culture). The strategy merging ProSeAM/MTase/SILAC (PMS) is uniquely versatile and programmable. We can choose suitable cell lines, subcellular fractions (i.e.; whole lysate or mitochondria), and genotypes as required. In particular, we would like to emphasize that the use of cell lysates derived from disease-associated MTase knockouts (KOs) holds vast potential to discover functionally unknown but biologically important methylation events. By adding ProSeAM and a recombinant MTase to the lysates derived from KO cells, we successfully characterized unprecedented nonhistone substrates of several MTases. Furthermore, this chemoproteomic procedure can be applied to explore MTase inhibitors (methylation brake). The combined strategy with ProSeAM/inhibitor/SILAC (PIS) offers intriguing opportunities to explore nonhistone methylation inhibitors.Considering that SAM is the second most widely used enzyme-substrate following ATP, the interdisciplinary research between chemistry and biology using SAM analogs has a potentially huge impact on a wide range of research fields associated with biological methylation. We hope that this Account will help to further delineate the biological function of this important class of enzymatic reaction.", "classifications": [ { "id": "Sodeoka", "label": "Group Sodeoka", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yoshihiro", "last_name": "Sohtome", "name": null }, { "creator_type": "author", "first_name": "Tadahiro", "last_name": "Shimazu", "name": null }, { "creator_type": "author", "first_name": "Yoichi", "last_name": "Shinkai", "name": null }, { "creator_type": "author", "first_name": "Mikiko", "last_name": "Sodeoka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/acs.accounts.1c00395" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "34612032" } }, "mesh": [ { "descriptor": "Biocatalysis", "descriptor_ui": "D055162", "major_topic": false }, { "descriptor": "Methyltransferases", "descriptor_ui": "D008780", "major_topic": false }, { "descriptor": "Molecular Structure", "descriptor_ui": "D015394", "major_topic": false }, { "descriptor": "Selenomethionine", "descriptor_ui": "D012645", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Oct 19", "date_precision": "day", "issue": "20", "normalized_date": "2021-10-19", "pages": "3818-3827", "proceedings_title": null, "publisher": "", "title": "Accounts of chemical research", "volume": "54", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Propargylic Se-adenosyl-l-selenomethionine: A Chemical Tool for Methylome Analysis.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "In this article, we report the use of randomly structured light illumination for chemical imaging of molecular distribution based on Raman microscopy with improved image resolution. Random structured basis images generated from temporal and spectral characteristics of the measured Raman signatures were superposed to perform structured illumination microscopy (SIM) with the blind-SIM algorithm. For experimental validation, Raman signatures corresponding to Rhodamine 6G (R6G) in the waveband of 730-760 nm and Raman shift in the range of 1096-1634 cm(-1) were extracted and reconstructed to build images of R6G. The results confirm improved image resolution using the concept and hints at super-resolution by almost twice better than the diffraction-limit.", "classifications": [ { "id": "Fujita", "label": "Group Fujita", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Hongki", "last_name": "Lee", "name": null }, { "creator_type": "author", "first_name": "Hajun", "last_name": "Yoo", "name": null }, { "creator_type": "author", "first_name": "Gwiyeong", "last_name": "Moon", "name": null }, { "creator_type": "author", "first_name": "Kar-Ann", "last_name": "Toh", "name": null }, { "creator_type": "author", "first_name": "Kentaro", "last_name": "Mochizuki", "name": null }, { "creator_type": "author", "first_name": "Katsumasa", "last_name": "Fujita", "name": null }, { "creator_type": "author", "first_name": "Donghyun", "last_name": "Kim", "name": null } ], "identifiers": { "doi": { "normalized": "10.1063/5.0064082" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "34654313" } }, "mesh": [], "publication": { "conference_name": null, "date": "2021 Oct 14", "date_precision": "day", "issue": "14", "normalized_date": "2021-10-14", "pages": "144202", "proceedings_title": null, "publisher": "", "title": "The Journal of chemical physics", "volume": "155", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Super-resolved Raman microscopy using random structured light illumination: Concept and feasibility.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Regnase-1 is an endoribonuclease crucial for controlling inflammation by degrading mRNAs encoding cytokines and inflammatory mediators in mammals. However, it is unclear how Regnase-1-mediated mRNA decay is controlled in interleukin (IL)-1beta- or Toll-like receptor (TLR) ligand-stimulated cells. Here, by analyzing the Regnase-1 interactome, we found that IL-1beta or TLR stimulus dynamically induced the formation of Regnase-1-beta-transducin repeat-containing protein (betaTRCP) complex. Importantly, we also uncovered a novel interaction between Regnase-1 and 14-3-3 in both mouse and human cells. In IL-1R/TLR-stimulated cells, the Regnase-1-14-3-3 interaction is mediated by IRAK1 through a previously uncharacterized C-terminal structural domain. Phosphorylation of Regnase-1 at S494 and S513 is critical for Regnase-1-14-3-3 interaction, while a different set of phosphorylation sites of Regnase-1 is known to be required for the recognition by betaTRCP and proteasome-mediated degradation. We found that Regnase-1-14-3-3 and Regnase-1-betaTRCP interactions are not sequential events. Rather, 14-3-3 protects Regnase-1 from betaTRCP-mediated degradation. On the other hand, 14-3-3 abolishes Regnase-1-mediated mRNA decay by inhibiting Regnase-1-mRNA association. In addition, nuclear-cytoplasmic shuttling of Regnase-1 is abrogated by 14-3-3 interaction. Taken together, the results suggest that a novel inflammation-induced interaction of 14-3-3 with Regnase-1 stabilizes inflammatory mRNAs by sequestering Regnase-1 in the cytoplasm to prevent mRNA recognition.", "classifications": [ { "id": "Mochizuki", "label": "Group Mochizuki", "parent": "Eiraku", "type": "group" }, { "id": "Eiraku", "label": "Team Eiraku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Kotaro", "last_name": "Akaki", "name": null }, { "creator_type": "author", "first_name": "Kosuke", "last_name": "Ogata", "name": null }, { "creator_type": "author", "first_name": "Yuhei", "last_name": "Yamauchi", "name": null }, { "creator_type": "author", "first_name": "Noriki", "last_name": "Iwai", "name": null }, { "creator_type": "author", "first_name": "Ka Man", "last_name": "Tse", "name": null }, { "creator_type": "author", "first_name": "Fabian", "last_name": "Hia", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Mochizuki", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Ishihama", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Mino", "name": null }, { "creator_type": "author", "first_name": "Osamu", "last_name": "Takeuchi", "name": null } ], "identifiers": { "doi": { "normalized": "10.7554/elife.71966" }, "pmcid": { "normalized": "PMC8553338" }, "pmid": { "normalized": "34636324" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Interleukin-1 Receptor-Associated Kinases", "descriptor_ui": "D053592", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Multiprotein Complexes", "descriptor_ui": "D046912", "major_topic": false }, { "descriptor": "Ribonucleases", "descriptor_ui": "D012260", "major_topic": false }, { "descriptor": "RNA Stability", "descriptor_ui": "D020871", "major_topic": false }, { "descriptor": "RNA, Messenger", "descriptor_ui": "D012333", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Oct 12", "date_precision": "day", "issue": "", "normalized_date": "2021-10-12", "pages": "e71966", "proceedings_title": null, "publisher": "", "title": "eLife", "volume": "10", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "IRAK1-dependent Regnase-1-14-3-3 complex formation controls Regnase-1-mediated mRNA decay.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Alkyne functional groups have Raman signatures in a region (1800 cm(-1) to 2800 cm(-1)) that is free from interference from cell components, known as the \"silent region\", and alkyne signals in this region were first utilized a decade ago to visualize the nuclear localization of a thymidine analogue EdU. Since then, the strategy of Raman imaging of biological samples by using alkyne functional groups, called alkyne-tag Raman imaging (ATRI), has become widely used. This article reviews the applications of ATRI in biological samples ranging from organelles to whole animal models, and briefly discusses the prospects for this technique.", "classifications": [ { "id": "JPMJCR1925", "label": "JPMJCR1925", "researcher": "Katsumasa Fujita", "type": "grant" }, { "id": "Fujita", "label": "Group Fujita", "parent": "Fujita", "type": "group" }, { "id": "Sodeoka", "label": "Group Sodeoka", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Subha", "last_name": "Bakthavatsalam", "name": null }, { "creator_type": "author", "first_name": "Kosuke", "last_name": "Dodo", "name": null }, { "creator_type": "author", "first_name": "Mikiko", "last_name": "Sodeoka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1039/d1cb00116g" }, "pmcid": { "normalized": "PMC8496067" }, "pmid": { "normalized": "34704046" } }, "mesh": [], "publication": { "conference_name": null, "date": "2021 Oct 7", "date_precision": "day", "issue": "5", "normalized_date": "2021-10-07", "pages": "1415-1429", "proceedings_title": null, "publisher": "", "title": "RSC chemical biology", "volume": "2", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "A decade of alkyne-tag Raman imaging (ATRI): applications in biological systems.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Alkynes were employed as tags to observe small molecules in cells by Raman microscopy. Herein, simple deuteration was found to shift the vibrational frequency of the alkyne by 135 cm(-1). Two-color Raman imaging of D-alkynes and H-alkynes made it possible to distinguish between and observe similar small molecules in live cells.", "classifications": [ { "id": "Sodeoka", "label": "Group Sodeoka", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Syusuke", "last_name": "Egoshi", "name": null }, { "creator_type": "author", "first_name": "Kosuke", "last_name": "Dodo", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Ohgane", "name": null }, { "creator_type": "author", "first_name": "Mikiko", "last_name": "Sodeoka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1039/d1ob01479j" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "34528645" } }, "mesh": [ { "descriptor": "Alkynes", "descriptor_ui": "D000480", "major_topic": true }, { "descriptor": "Deuterium", "descriptor_ui": "D003903", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Molecular Structure", "descriptor_ui": "D015394", "major_topic": false }, { "descriptor": "Spectrum Analysis, Raman", "descriptor_ui": "D013059", "major_topic": true } ], "publication": { "conference_name": null, "date": "2021 Oct 6", "date_precision": "day", "issue": "38", "normalized_date": "2021-10-06", "pages": "8232-8236", "proceedings_title": null, "publisher": "", "title": "Organic & biomolecular chemistry", "volume": "19", "year": 2021 }, "ssbd": { "database": [ "ssbd-database-000227" ], "repository": [ "ssbd-repos-000227" ] }, "title": "Deuteration of terminal alkynes realizes simultaneous live cell Raman imaging of similar alkyne-tagged biomolecules.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Photosensory adaptation, which can be classified as sensor or effector adaptation, optimizes the light sensing of living organisms by tuning their sensitivity to changing light conditions. During the phototropic response in Arabidopsis (Arabidopsis thaliana), the light-dependent expression controls of blue-light (BL) photoreceptor phototropin 1 (phot1) and its modulator ROOT PHOTOTROPISM2 (RPT2) are known as the molecular mechanisms underlying sensor adaptation. However, little is known about effector adaption in plant phototropism. Here, we show that control of the phosphorylation status of NONPHOTOTROPIC HYPOCOTYL3 (NPH3) leads to effector adaptation in hypocotyl phototropism. We generated unphosphorable and phosphomimetic NPH3 proteins on seven phosphorylation sites in the etiolated seedlings of Arabidopsis. Unphosphorable NPH3 showed a shortening of its retention time in the cytosol and caused an inability to adapt to very low fluence rates of BL ( approximately 10-5 micromol m-2 s-1) during the phototropic response. In contrast, the phosphomimetic NPH3 proteins had a lengthened retention time in the cytosol and could not enable the adaptation to BL at fluence rates of 10-3 micromol m-2 s-1 or more. Our results indicate that the activation level of phot1 and the corresponding phosphorylation level of NPH3 determine the dissociation rate and the reassociation rate of NPH3 on the plasma membrane, respectively. These mechanisms may moderately maintain the active state of phot1 signaling across a broad range of BL intensities and contribute to the photosensory adaptation of phot1 signaling during the phototropic response in hypocotyls.", "classifications": [ { "id": "Higaki", "label": "Group Higaki", "parent": "Ueda", "type": "group" }, { "id": "Ueda", "label": "Team Ueda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Taro", "last_name": "Kimura", "name": null }, { "creator_type": "author", "first_name": "Ken", "last_name": "Haga", "name": null }, { "creator_type": "author", "first_name": "Yuko", "last_name": "Nomura", "name": null }, { "creator_type": "author", "first_name": "Takumi", "last_name": "Higaki", "name": null }, { "creator_type": "author", "first_name": "Hirofumi", "last_name": "Nakagami", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Sakai", "name": null } ], "identifiers": { "doi": { "normalized": "10.1093/plphys/kiab281" }, "pmcid": { "normalized": "PMC8491083" }, "pmid": { "normalized": "34608954" } }, "mesh": [ { "descriptor": "Arabidopsis", "descriptor_ui": "D017360", "major_topic": true }, { "descriptor": "Arabidopsis Proteins", "descriptor_ui": "D029681", "major_topic": false }, { "descriptor": "Phosphorylation", "descriptor_ui": "D010766", "major_topic": false }, { "descriptor": "Phototropism", "descriptor_ui": "D018524", "major_topic": true }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Oct 5", "date_precision": "day", "issue": "2", "normalized_date": "2021-10-05", "pages": "981-995", "proceedings_title": null, "publisher": "", "title": "Plant physiology", "volume": "187", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Phosphorylation of NONPHOTOTROPIC HYPOCOTYL3 affects photosensory adaptation during the phototropic response.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Stimulation of cells by nanosecond pulsed electric fields (nsPEFs) has attracted attention as a technology for medical applications such as cancer treatment. nsPEFs have been shown to affect intracellular environments without significant damage to cell membranes; however, the mechanism underlying the effect of nsPEFs on cells remains unclear. In this study, we constructed electrodes for applying nsPEFs and analyzed the change in volume of a single cell due to nsPEFs using fluorescence and Raman microscopy. It was shown that the direction of the change depended on the applied electric field; expansion due to the influx of water was observed at high electric field, and cell shrinkage was observed at low electric field. The change in cell volume was correlated to the change in the intracellular Ca(2+) concentration, and nsPEFs-induced shrinking was not observed when the Ca(2+)-free medium was used. This result suggests that the cell shrinkage is related to the regulatory volume decrease where the cell adjusts the increase in intracellular Ca(2+) concentration, inducing the efflux of ions and water from the cell.", "classifications": [ { "id": "Nakabayashi", "label": "Group Nakabayashi", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Qi", "last_name": "Yang", "name": null }, { "creator_type": "author", "first_name": "Shinji", "last_name": "Kajimoto", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Hirotsugu", "last_name": "Hiramatsu", "name": null }, { "creator_type": "author", "first_name": "Takakazu", "last_name": "Nakabayashi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/acs.jpcb.1c06058" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "34519209" } }, "mesh": [ { "descriptor": "Cell Size", "descriptor_ui": "D048429", "major_topic": false }, { "descriptor": "Electricity", "descriptor_ui": "D004560", "major_topic": true } ], "publication": { "conference_name": null, "date": "2021 Sep 30", "date_precision": "day", "issue": "38", "normalized_date": "2021-09-30", "pages": "10692-10700", "proceedings_title": null, "publisher": "", "title": "The journal of physical chemistry. B", "volume": "125", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Regulation of Cell Volume by Nanosecond Pulsed Electric Fields.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Acute kidney injury (AKI) is defined as a rapid decline in kidney function. The associated syndromes may lead to increased morbidity and mortality, but its early detection remains difficult. Using capillary electrophoresis time-of-flight mass spectrometry (CE-TOFMS), we analyzed the urinary metabolomic profile of patients admitted to the intensive care unit (ICU) after invasive surgery. Urine samples were collected at six time points: before surgery, at ICU admission and 6, 12, 24 and 48 h after. First, urine samples from 61 initial patients (non-AKI: 23, mild AKI: 24, severe AKI: 14) were measured, followed by the measurement of urine samples from 60 additional patients (non-AKI: 40, mild AKI: 20). Glycine and ethanolamine were decreased in patients with AKI compared with non-AKI patients at 6-24 h in the two groups. The linear statistical model constructed at each time point by machine learning achieved the best performance at 24 h (median AUC, area under the curve: 89%, cross-validated) for the 1st group. When cross-validated between the two groups, the AUC showed the best value of 70% at 12 h. These results identified metabolites and time points that show patterns specific to subjects who develop AKI, paving the way for the development of better biomarkers.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Rintaro", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Akiyoshi", "last_name": "Hirayama", "name": null }, { "creator_type": "author", "first_name": "Arisa", "last_name": "Akiba", "name": null }, { "creator_type": "author", "first_name": "Yushi", "last_name": "Kamei", "name": null }, { "creator_type": "author", "first_name": "Yuyu", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Satsuki", "last_name": "Ikeda", "name": null }, { "creator_type": "author", "first_name": "Brian", "last_name": "Kwan", "name": null }, { "creator_type": "author", "first_name": "Minya", "last_name": "Pu", "name": null }, { "creator_type": "author", "first_name": "Loki", "last_name": "Natarajan", "name": null }, { "creator_type": "author", "first_name": "Hibiki", "last_name": "Shinjo", "name": null }, { "creator_type": "author", "first_name": "Shin'ichi", "last_name": "Akiyama", "name": null }, { "creator_type": "author", "first_name": "Masaru", "last_name": "Tomita", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Shoichi", "last_name": "Maruyama", "name": null } ], "identifiers": { "doi": { "normalized": "10.3390/metabo11100671" }, "pmcid": { "normalized": "PMC8540909" }, "pmid": { "normalized": "34677386" } }, "mesh": [], "publication": { "conference_name": null, "date": "2021 Sep 30", "date_precision": "day", "issue": "10", "normalized_date": "2021-09-30", "pages": "", "proceedings_title": null, "publisher": "", "title": "Metabolites", "volume": "11", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Urinary Metabolome Analyses of Patients with Acute Kidney Injury Using Capillary Electrophoresis-Mass Spectrometry.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Targeted sequencing for somatic mutations across the hotspots of 50 cancer-related genes was performed using biopsy specimens to investigate whether clinicopathological factors and genomic alterations correlated with prognosis in locally advanced cervical cancer. Seventy patients diagnosed with International Federation of Obstetrics and Gynecology (FIGO) stage III to IVA cervical cancer underwent radiotherapy or concurrent chemoradiotherapy at the National Cancer Center Hospital between January 2008 and December 2017. Mutations were detected in 47 of 70 [67% of cases; frequency of genetic alterations was as follows: PIK3CA (51%), FBXW7 (10%), PTEN (7.1%), and TP53 (5.7%)]. The Cancer Genome Atlas (TCGA) datasets showed a similar distribution of somatic mutations, but PIK3CA mutation frequency was significantly higher in our cohort than in TCGA datasets (P = 0.028). Patients with TP53 mutation were significantly related to poor progression-free survival (PFS) (hazard ratio [HR] = 3.53, P = 0.042). Patients with tumor diameters > 70 mm were associated with poor prognosis (HR = 2.96, P = 0.0048). Patients with non-HPV16/18 genotypes had worse prognosis than those with HPV16/18 genotypes (HR = 2.15, P = 0.030). Hence, patients with locally advanced cervical cancer, TP53 mutation, large tumor diameter, and non-HPV16/18 genotype were independently correlated with poor PFS, despite concurrent chemoradiotherapy.", "classifications": [ { "id": "Hamamoto", "label": "Group Hamamoto", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Ikumi", "last_name": "Kuno", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Takayanagi", "name": null }, { "creator_type": "author", "first_name": "Yuka", "last_name": "Asami", "name": null }, { "creator_type": "author", "first_name": "Naoya", "last_name": "Murakami", "name": null }, { "creator_type": "author", "first_name": "Maiko", "last_name": "Matsuda", "name": null }, { "creator_type": "author", "first_name": "Yoko", "last_name": "Shimada", "name": null }, { "creator_type": "author", "first_name": "Sou", "last_name": "Hirose", "name": null }, { "creator_type": "author", "first_name": "Mayumi Kobayashi", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Masaaki", "last_name": "Komatsu", "name": null }, { "creator_type": "author", "first_name": "Ryuji", "last_name": "Hamamoto", "name": null }, { "creator_type": "author", "first_name": "Kae", "last_name": "Okuma", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Kohno", "name": null }, { "creator_type": "author", "first_name": "Jun", "last_name": "Itami", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Kouya", "last_name": "Shiraishi", "name": null }, { "creator_type": "author", "first_name": "Tomoyasu", "last_name": "Kato", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41598-021-98527-2" }, "pmcid": { "normalized": "PMC8478905" }, "pmid": { "normalized": "34584128" } }, "mesh": [ { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Aged, 80 and over", "descriptor_ui": "D000369", "major_topic": false }, { "descriptor": "Alphapapillomavirus", "descriptor_ui": "D052685", "major_topic": false }, { "descriptor": "Cervix Uteri", "descriptor_ui": "D002584", "major_topic": false }, { "descriptor": "Chemoradiotherapy", "descriptor_ui": "D059248", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Follow-Up Studies", "descriptor_ui": "D005500", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": false }, { "descriptor": "Neoplasm Staging", "descriptor_ui": "D009367", "major_topic": false }, { "descriptor": "Papillomavirus Infections", "descriptor_ui": "D030361", "major_topic": false }, { "descriptor": "Prognosis", "descriptor_ui": "D011379", "major_topic": false }, { "descriptor": "Progression-Free Survival", "descriptor_ui": "D000077982", "major_topic": false }, { "descriptor": "Risk Factors", "descriptor_ui": "D012307", "major_topic": false }, { "descriptor": "Tumor Burden", "descriptor_ui": "D047368", "major_topic": false }, { "descriptor": "Tumor Suppressor Protein p53", "descriptor_ui": "D016159", "major_topic": false }, { "descriptor": "Uterine Cervical Neoplasms", "descriptor_ui": "D002583", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Sep 28", "date_precision": "day", "issue": "1", "normalized_date": "2021-09-28", "pages": "19261", "proceedings_title": null, "publisher": "", "title": "Scientific reports", "volume": "11", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "TP53 mutants and non-HPV16/18 genotypes are poor prognostic factors for concurrent chemoradiotherapy in locally advanced cervical cancer.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Despite the availability of vaccines that efficiently reduce the severity of clinical symptoms, influenza viruses still cause substantial morbidity and mortality worldwide. In this regard, nasal influenza vaccines-because they induce virus-specific IgA-may be more effective than traditional parenteral formulations in preventing infection of the upper respiratory tract. In addition, the neuraminidase (NA) of influenza virus has shown promise as a vaccine antigen to confer broad cross-protection, in contrast to hemagglutinin (HA), the target of most current vaccines, which undergoes frequent antigenic changes, leading to vaccine ineffectiveness against mismatched heterologous strains. However, the usefulness of NA as an antigen for nasal vaccines is unclear. Here, we compared NA and HA as antigens for nasal vaccines in mice. Intranasal immunization with recombinant NA (rNA) plus adjuvant protected mice against not only homologous but also heterologous virus challenge in the upper respiratory tract, whereas intranasal immunization with rHA failed to protect against heterologous challenge. In addition, intranasal immunization with rNA, but not rHA, conferred cross-protection even in the absence of adjuvant in virus infection-experienced mice; this strong cross-protection was due to the broader capacity of NA-specific antibodies to bind to heterologous virus. Furthermore, the NA-specific IgA in the upper respiratory tract that was induced through rNA intranasal immunization recognized more epitopes than did the NA-specific IgG and IgA in plasma, again increasing cross-protection. Together, our findings suggest the potential of NA as an antigen for nasal vaccines to provide broad cross-protection against both homologous and heterologous influenza viruses. IMPORTANCE Because mismatch between vaccine strains and epidemic strains cannot always be avoided, the development of influenza vaccines that induce broad cross-protection against antigenically mismatched heterologous strains is needed. Although the importance of NA-specific antibodies to cross-protection in humans and experimental animals is becoming clear, the potential of NA as an antigen for providing cross-protection through nasal vaccines is unknown. We show here that intranasal immunization with NA confers broad cross-protection in the upper respiratory tract, where virus transmission is initiated, by inducing NA-specific IgA that recognizes a wide range of epitopes. These data shed new light on NA-based nasal vaccines as powerful anti-influenza tools that confer broad cross-protection.", "classifications": [ { "id": "Yamamoto", "label": "Group Yamamoto", "parent": "Toyoshima", "type": "group" }, { "id": "Toyoshima", "label": "Team Toyoshima", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Xun", "last_name": "Sun", "name": null }, { "creator_type": "author", "first_name": "Jonas", "last_name": "Alfermann", "name": null }, { "creator_type": "author", "first_name": "Hao", "last_name": "Li", "name": null }, { "creator_type": "author", "first_name": "Maxwell B.", "last_name": "Watkins", "name": null }, { "creator_type": "author", "first_name": "Yi-Tsao", "last_name": "Chen", "name": null }, { "creator_type": "author", "first_name": "Thomas E.", "last_name": "Morrell", "name": null }, { "creator_type": "author", "first_name": "Florian", "last_name": "Mayerthaler", "name": null }, { "creator_type": "author", "first_name": "Chia-Ying", "last_name": "Wang", "name": null }, { "creator_type": "author", "first_name": "Tamiki", "last_name": "Komatsuzaki", "name": null }, { "creator_type": "author", "first_name": "Jhih-Wei", "last_name": "Chu", "name": null }, { "creator_type": "author", "first_name": "Nozomi", "last_name": "Ando", "name": null }, { "creator_type": "author", "first_name": "Henning D.", "last_name": "Mootz", "name": null }, { "creator_type": "author", "first_name": "Haw", "last_name": "Yang", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Kawai", "name": null }, { "creator_type": "author", "first_name": "Yasuyuki", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Takuto", "last_name": "Nogimori", "name": null }, { "creator_type": "author", "first_name": "Kohei", "last_name": "Takeshita", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Yasuo", "last_name": "Yoshioka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1128/jvi.01180-21" }, "pmcid": { "normalized": "PMC8475506" }, "pmid": { "normalized": "34379511" } }, "mesh": [ { "descriptor": "Adjuvants, Immunologic", "descriptor_ui": "D000276", "major_topic": false }, { "descriptor": "Administration, Intranasal", "descriptor_ui": "D000281", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Antibodies, Viral", "descriptor_ui": "D000914", "major_topic": false }, { "descriptor": "Cross Protection", "descriptor_ui": "D056738", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Hemagglutinin Glycoproteins, Influenza Virus", "descriptor_ui": "D019267", "major_topic": false }, { "descriptor": "Hemagglutinins", "descriptor_ui": "D006388", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Influenza A Virus, H1N1 Subtype", "descriptor_ui": "D053118", "major_topic": false }, { "descriptor": "Influenza Vaccines", "descriptor_ui": "D007252", "major_topic": false }, { "descriptor": "Influenza, Human", "descriptor_ui": "D007251", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Neuraminidase", "descriptor_ui": "D009439", "major_topic": false }, { "descriptor": "Orthomyxoviridae", "descriptor_ui": "D009975", "major_topic": false }, { "descriptor": "Orthomyxoviridae Infections", "descriptor_ui": "D009976", "major_topic": false }, { "descriptor": "Vaccination", "descriptor_ui": "D014611", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Sep 27", "date_precision": "day", "issue": "20", "normalized_date": "2021-09-27", "pages": "e0118021", "proceedings_title": null, "publisher": "", "title": "Journal of virology", "volume": "95", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "The Potential of Neuraminidase as an Antigen for Nasal Vaccines To Increase Cross-Protection against Influenza Viruses.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The shoot organ boundaries have important roles in plant growth and morphogenesis. It has been reported that a gene encoding a cysteine-rich secreted peptide of the EPIDERMAL PATTERNING FACTOR-LIKE (EPFL) family, EPFL2, is expressed in the boundary domain between the two cotyledon primordia of Arabidopsis thaliana embryo. However, its developmental functions remain unknown. This study aimed to analyze the role of EPFL2 during embryogenesis. We found that cotyledon growth was reduced in its loss-of-function mutants, and this phenotype was associated with the reduction of auxin response peaks at the tips of the primordia. The reduced cotyledon size of the mutant embryo recovered in germinating seedlings, indicating the presence of a factor that acted redundantly with EPFL2 to promote cotyledon growth in late embryogenesis. Our analysis suggests that the boundary domain between the cotyledon primordia acts as a signaling center that organizes auxin response peaks and promotes cotyledon growth.", "classifications": [ { "id": "Higaki", "label": "Group Higaki", "parent": "Ueda", "type": "group" }, { "id": "Ueda", "label": "Team Ueda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Rina", "last_name": "Fujihara", "name": null }, { "creator_type": "author", "first_name": "Naoyuki", "last_name": "Uchida", "name": null }, { "creator_type": "author", "first_name": "Toshiaki", "last_name": "Tameshige", "name": null }, { "creator_type": "author", "first_name": "Nozomi", "last_name": "Kawamoto", "name": null }, { "creator_type": "author", "first_name": "Yugo", "last_name": "Hotokezaka", "name": null }, { "creator_type": "author", "first_name": "Takumi", "last_name": "Higaki", "name": null }, { "creator_type": "author", "first_name": "Rudiger", "last_name": "Simon", "name": null }, { "creator_type": "author", "first_name": "Keiko U.", "last_name": "Torii", "name": null }, { "creator_type": "author", "first_name": "Masao", "last_name": "Tasaka", "name": null }, { "creator_type": "author", "first_name": "Mitsuhiro", "last_name": "Aida", "name": null } ], "identifiers": { "doi": { "normalized": "10.5511/plantbiotechnology.21.0508a" }, "pmcid": { "normalized": "PMC8562585" }, "pmid": { "normalized": "34782818" } }, "mesh": [], "publication": { "conference_name": null, "date": "2021 Sep 25", "date_precision": "day", "issue": "3", "normalized_date": "2021-09-25", "pages": "317-322", "proceedings_title": null, "publisher": "", "title": "Plant biotechnology (Tokyo, Japan)", "volume": "38", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "The boundary-expressed EPIDERMAL PATTERNING FACTOR-LIKE2 gene encoding a signaling peptide promotes cotyledon growth during Arabidopsis thaliana embryogenesis.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Secondary cell walls (SCWs) accumulate in specific cell types of vascular plants, notably xylem vessel cells. Previous work has shown that calcium ions (Ca(2+)) participate in xylem vessel cell differentiation, but whether they function in SCW deposition remains unclear. In this study, we examined the role of Ca(2+) in SCW deposition during xylem vessel cell differentiation using Arabidopsis thaliana suspension-cultured cells carrying the VND7-inducible system, in which VND7 activity can be post-translationally upregulated to induce transdifferentiation into protoxylem-type vessel cells. We observed that extracellular Ca(2+) concentration was a crucial determinant of differentiation, although it did not have consistent effects on the transcription of VND7-downstream genes as a whole. Increasing the Ca(2+) concentration reduced differentiation but the cells could generate the spiral patterning of SCWs. Exposure to a calcium-channel inhibitor partly restored differentiation but resulted in abnormal branched and net-like SCW patterning. These data suggest that Ca(2+) signaling participates in xylem vessel cell differentiation via post-transcriptional regulation of VND7-downstream events, such as patterning of SCW deposition.", "classifications": [ { "id": "Higaki", "label": "Group Higaki", "parent": "Ueda", "type": "group" }, { "id": "Ueda", "label": "Team Ueda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Eri", "last_name": "Kamon", "name": null }, { "creator_type": "author", "first_name": "Chihiro", "last_name": "Noda", "name": null }, { "creator_type": "author", "first_name": "Takumi", "last_name": "Higaki", "name": null }, { "creator_type": "author", "first_name": "Taku", "last_name": "Demura", "name": null }, { "creator_type": "author", "first_name": "Misato", "last_name": "Ohtani", "name": null } ], "identifiers": { "doi": { "normalized": "10.5511/plantbiotechnology.21.0519a" }, "pmcid": { "normalized": "PMC8562575" }, "pmid": { "normalized": "34782820" } }, "mesh": [], "publication": { "conference_name": null, "date": "2021 Sep 25", "date_precision": "day", "issue": "3", "normalized_date": "2021-09-25", "pages": "331-337", "proceedings_title": null, "publisher": "", "title": "Plant biotechnology (Tokyo, Japan)", "volume": "38", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Calcium signaling contributes to xylem vessel cell differentiation via post-transcriptional regulation of VND7 downstream events.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Cell signaling and the following gene regulation are tightly regulated to keep homeostasis. NF-kappaB is a famous key transcription factor for inflammatory cell regulations that obtain a closed feedback loop with IkappaB. Similarly, we show here, NFAT is also tightly regulated via its downstream target, down syndrome critical region (DSCR)-1. In primary cultured endothelium, either shear stress or VEGF treatment revealed quick NFAT1 nuclear localization following the DSCR-1 transactivation, which in turn induced NFAT1 cytoplasm sequestration. Interestingly, both NFAT and DSCR-1 can be competitive substrates for calcineurin phosphatase and DSCR-1 is known to unstable protein, which caused NFAT1-nucleocytoplasmic damped oscillation via sustained shear stress or VEGF stimulation in endothelial cell (EC)s. To understand the molecular mechanism underlying the NFAT1 oscillation, we built a mathematical model of spatiotemporal regulation of NFAT1 combined with calcineurin and DSCR-1. Theoretically, manipulation of DSCR-1 expression in simulation predicted that DSCR-1 reduction would cause nuclear retention of dephosphorylated NFAT1 and disappearance of NFAT1 oscillation. To confirm this in ECs, DSCR-1 knockdown analysis was performed. DSCR-1 reduction indeed increased dephosphorylated NFAT1 in both the nucleus and cytoplasm, which eventually led to nuclear retention of NFAT1. Taken together, these studies suggest that DSCR-1 is a responsible critical factor for NFAT1 nucleocytoplasmic oscillation in shear stress or VEGF treated ECs. Our mathematical model successfully reproduced the experimental observations of NFAT1 dynamics. Combined mathematical and experimental approaches would provide a quantitative understanding way for the spatiotemporal NFAT1 feedback system.", "classifications": [ { "id": "Suzuki", "label": "Group Suzuki", "parent": "Takekawa", "type": "group" }, { "id": "Takekawa", "label": "Team Takekawa", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Masashi", "last_name": "Muramatsu", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Hokuto", "last_name": "Shimoji", "name": null }, { "creator_type": "author", "first_name": "Miko", "last_name": "Komiya", "name": null }, { "creator_type": "author", "first_name": "Yuri", "last_name": "Miyamura", "name": null }, { "creator_type": "author", "first_name": "Koichi", "last_name": "Nishiyama", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Minami", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.bbrc.2021.07.072" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "34332425" } }, "mesh": [ { "descriptor": "Active Transport, Cell Nucleus", "descriptor_ui": "D021581", "major_topic": false }, { "descriptor": "Calcineurin", "descriptor_ui": "D019703", "major_topic": false }, { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "DNA-Binding Proteins", "descriptor_ui": "D004268", "major_topic": false }, { "descriptor": "Endothelial Cells", "descriptor_ui": "D042783", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Muscle Proteins", "descriptor_ui": "D009124", "major_topic": false }, { "descriptor": "NFATC Transcription Factors", "descriptor_ui": "D050778", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Sep 24", "date_precision": "day", "issue": "", "normalized_date": "2021-09-24", "pages": "201-209", "proceedings_title": null, "publisher": "", "title": "Biochemical and biophysical research communications", "volume": "571", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "NFAT indicates nucleocytoplasmic damped oscillation via its feedback modulator.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Human pluripotent stem cells (hPSCs) are grouped into two cell types; embryonic stem cells (hESCs) and induced pluripotent stem cells (hiPSCs). hESCs have provided multiple powerful platforms to study human biology, including human development and diseases; however, there were difficulties in the establishment of hESCs from human embryo and concerns over its ethical issues. The discovery of hiPSCs has expanded to various applications in no time because hiPSCs had already overcome these problems. Many hPSC-based studies have been performed using two-dimensional monocellular culture methods at the cellular level. However, in many physiological and pathophysiological conditions, intra- and inter-organ interactions play an essential role, which has hampered the establishment of an appropriate study model. Therefore, the application of recently developed technologies, such as three-dimensional organoids, bioengineering, and organ-on-a-chip technology, has great potential for constructing multicellular tissues, generating the functional organs from hPSCs, and recapitulating complex tissue functions for better biological research and disease modeling. Moreover, emerging techniques, such as single-cell transcriptomics, spatial transcriptomics, and artificial intelligence (AI) allowed for a denser and more precise analysis of such heterogeneous and complex tissues. Here, we review the applications of hPSCs to construct complex organs and discuss further prospects of disease modeling and drug discovery based on these PSC-derived organs.", "classifications": [ { "id": "Yamamoto", "label": "Group Yamamoto", "parent": "Toyoshima", "type": "group" }, { "id": "Toyoshima", "label": "Team Toyoshima", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Ryusaku", "last_name": "Matsumoto", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Yutaka", "last_name": "Takahashi", "name": null } ], "identifiers": { "doi": { "normalized": "10.3390/ijms221910184" }, "pmcid": { "normalized": "PMC8508560" }, "pmid": { "normalized": "34638524" } }, "mesh": [ { "descriptor": "Biomedical Research", "descriptor_ui": "D035843", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Central Nervous System", "descriptor_ui": "D002490", "major_topic": false }, { "descriptor": "Coculture Techniques", "descriptor_ui": "D018920", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Induced Pluripotent Stem Cells", "descriptor_ui": "D057026", "major_topic": false }, { "descriptor": "Organoids", "descriptor_ui": "D009940", "major_topic": false }, { "descriptor": "Synthetic Biology", "descriptor_ui": "D058615", "major_topic": false }, { "descriptor": "Tissue Engineering", "descriptor_ui": "D023822", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Sep 22", "date_precision": "day", "issue": "19", "normalized_date": "2021-09-22", "pages": "10184", "proceedings_title": null, "publisher": "", "title": "International journal of molecular sciences", "volume": "22", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Complex Organ Construction from Human Pluripotent Stem Cells for Biological Research and Disease Modeling with New Emerging Techniques.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Multicomponent crystallization is universally important in various research fields including materials science as well as biology and geology, and presents new opportunities in crystal engineering. This process includes multiple kinetic and thermodynamic events that compete with each other, wherein \"external triggers\" often help the system select appropriate pathways for constructing desired structures. Here we report an unprecedented finding that a lattice strain accumulated with the growth of a crystal serves as an \"internal trigger\" for pathway selection in multicomponent crystallization. We discovered a \"spontaneous\" crystal transition, where the kinetically preferred layered crystal, initially formed by excluding the pillar component, carries a single dislocation at its geometrical center. This crystal \"spontaneously\" liberates a core region to relieve the accumulated lattice strain around the dislocation. Consequently, the liberated part becomes dynamic and enables the pillar ligand to invade the crystalline lattice, thereby transforming into a thermodynamically preferred pillared-layer crystal.", "classifications": [ { "id": "Hijikata", "label": "Group Hijikata", "parent": "Tsuchiya", "type": "group" }, { "id": "Tsuchiya", "label": "Team Tsuchiya", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Hubiao", "last_name": "Huang", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Jenny", "last_name": "Pirillo", "name": null }, { "creator_type": "author", "first_name": "Yuh", "last_name": "Hijikata", "name": null }, { "creator_type": "author", "first_name": "Yong Sheng", "last_name": "Zhao", "name": null }, { "creator_type": "author", "first_name": "Stephen Z. D.", "last_name": "Cheng", "name": null }, { "creator_type": "author", "first_name": "Takuzo", "last_name": "Aida", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/jacs.1c06854" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "34506155" } }, "mesh": [], "publication": { "conference_name": null, "date": "2021 Sep 22", "date_precision": "day", "issue": "37", "normalized_date": "2021-09-22", "pages": "15319-15325", "proceedings_title": null, "publisher": "", "title": "Journal of the American Chemical Society", "volume": "143", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Accumulated Lattice Strain as an Internal Trigger for Spontaneous Pathway Selection.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: Intra-tumor heterogeneity (ITH) encompasses cellular differences in tumors and is related to clinical outcomes such as drug resistance. However, little is known about the dynamics of ITH, owing to the lack of time-series analysis at the single-cell level. Mouse models that recapitulate cancer development are useful for controlled serial time sampling. RESULTS: We performed single-cell exome and transcriptome sequencing of 200 cells to investigate how ITH is generated in a mouse colorectal cancer model. In the model, a single normal intestinal cell is grown into organoids that mimic the intestinal crypt structure. Upon RNAi-mediated downregulation of a tumor suppressor gene APC, the transduced organoids were serially transplanted into mice to allow exposure to in vivo microenvironments, which play relevant roles in cancer development. The ITH of the transcriptome increased after the transplantation, while that of the exome decreased. Mutations generated during organoid culture did not greatly change at the bulk-cell level upon the transplantation. The RNA ITH increase was due to the emergence of new transcriptional subpopulations. In contrast to the initial cells expressing mesenchymal-marker genes, new subpopulations repressed these genes after the transplantation. Analyses of colorectal cancer data from The Cancer Genome Atlas revealed a high proportion of metastatic cases in human subjects with expression patterns similar to the new cell subpopulations in mouse. These results suggest that the birth of transcriptional subpopulations may be a key for adaptation to drastic micro-environmental changes when cancer cells have sufficient genetic alterations at later tumor stages. CONCLUSIONS: This study revealed an evolutionary dynamics of single-cell RNA and DNA heterogeneity in tumor progression, giving insights into the mesenchymal-epithelial transformation of tumor cells at metastasis in colorectal cancer.", "classifications": [ { "id": "Okamoto", "label": "Group Okamoto", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Hanako", "last_name": "Ono", "name": null }, { "creator_type": "author", "first_name": "Yasuhito", "last_name": "Arai", "name": null }, { "creator_type": "author", "first_name": "Eisaku", "last_name": "Furukawa", "name": null }, { "creator_type": "author", "first_name": "Daichi", "last_name": "Narushima", "name": null }, { "creator_type": "author", "first_name": "Tetsuya", "last_name": "Matsuura", "name": null }, { "creator_type": "author", "first_name": "Hiromi", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Shiokawa", "name": null }, { "creator_type": "author", "first_name": "Momoko", "last_name": "Nagai", "name": null }, { "creator_type": "author", "first_name": "Toshio", "last_name": "Imai", "name": null }, { "creator_type": "author", "first_name": "Koshi", "last_name": "Mimori", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Okamoto", "name": null }, { "creator_type": "author", "first_name": "Yoshitaka", "last_name": "Hippo", "name": null }, { "creator_type": "author", "first_name": "Tatsuhiro", "last_name": "Shibata", "name": null }, { "creator_type": "author", "first_name": "Mamoru", "last_name": "Kato", "name": null } ], "identifiers": { "doi": { "normalized": "10.1186/s12915-021-01147-5" }, "pmcid": { "normalized": "PMC8456589" }, "pmid": { "normalized": "34548081" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Colorectal Neoplasms", "descriptor_ui": "D015179", "major_topic": true }, { "descriptor": "DNA", "descriptor_ui": "D004247", "major_topic": false }, { "descriptor": "Exome", "descriptor_ui": "D059472", "major_topic": false }, { "descriptor": "Genetic Heterogeneity", "descriptor_ui": "D018740", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "RNA", "descriptor_ui": "D012313", "major_topic": false }, { "descriptor": "Sequence Analysis, RNA", "descriptor_ui": "D017423", "major_topic": false }, { "descriptor": "Tumor Microenvironment", "descriptor_ui": "D059016", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Sep 21", "date_precision": "day", "issue": "1", "normalized_date": "2021-09-21", "pages": "207", "proceedings_title": null, "publisher": "", "title": "BMC biology", "volume": "19", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Single-cell DNA and RNA sequencing reveals the dynamics of intra-tumor heterogeneity in a colorectal cancer model.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "5-aminolevulinic acid (5-ALA)-induced protoporphyrin IX (PpIX) fluorescence is widely used for the intraoperative detection of malignant tumors. However, the fluorescence emission profiles of the accompanying necrotic regions of these tumors have yet to be determined. To address this, we performed fluorescence and high-performance liquid chromatography (HPLC) analyses of necrotic tissues of squamous cancer after 5-ALA administration. In resected human lymph nodes of metastatic squamous cell carcinoma, we found a fluorescence peak at approximately 620 nm in necrotic lesions, which was distinct from the PpIX fluorescence peak at 635 nm for viable cancer lesions. Necrotic lesions obtained from a subcutaneous xenograft model of human B88 oral squamous cancer also emitted the characteristic fluorescence peak at 620 nm after light irradiation: the fluorescence intensity ratio (620 nm/635 nm) increased with the energy of the irradiation light. HPLC analysis revealed a high content ratio of uroporphyrin I (UPI)/total porphyrins in the necrotic cores of murine tumors, indicating that UPI is responsible for the 620 nm peak. UPI accumulation in necrotic tissues after 5-ALA administration was possibly due to the failure of the heme biosynthetic pathway. Taken together, fluorescence imaging of UPI after 5-ALA administration may be applicable for the evaluation of tumor necrosis.", "classifications": [ { "id": "Tanaka", "label": "Group Tanaka", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Masatomo", "last_name": "Beika", "name": null }, { "creator_type": "author", "first_name": "Yoshinori", "last_name": "Harada", "name": null }, { "creator_type": "author", "first_name": "Takeo", "last_name": "Minamikawa", "name": null }, { "creator_type": "author", "first_name": "Yoshihisa", "last_name": "Yamaoka", "name": null }, { "creator_type": "author", "first_name": "Noriaki", "last_name": "Koizumi", "name": null }, { "creator_type": "author", "first_name": "Yasutoshi", "last_name": "Murayama", "name": null }, { "creator_type": "author", "first_name": "Hirotaka", "last_name": "Konishi", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Shiozaki", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Fujiwara", "name": null }, { "creator_type": "author", "first_name": "Eigo", "last_name": "Otsuji", "name": null }, { "creator_type": "author", "first_name": "Tetsuro", "last_name": "Takamatsu", "name": null }, { "creator_type": "author", "first_name": "Hideo", "last_name": "Tanaka", "name": null } ], "identifiers": { "doi": { "normalized": "10.3390/ijms221810121" }, "pmcid": { "normalized": "PMC8471361" }, "pmid": { "normalized": "34576284" } }, "mesh": [ { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Aminolevulinic Acid", "descriptor_ui": "D000622", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Carcinoma, Squamous Cell", "descriptor_ui": "D002294", "major_topic": false }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Chromatography, High Pressure Liquid", "descriptor_ui": "D002851", "major_topic": false }, { "descriptor": "Disease Models, Animal", "descriptor_ui": "D004195", "major_topic": false }, { "descriptor": "Esophageal Neoplasms", "descriptor_ui": "D004938", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Models, Biological", "descriptor_ui": "D008954", "major_topic": false }, { "descriptor": "Necrosis", "descriptor_ui": "D009336", "major_topic": false }, { "descriptor": "Spectrometry, Fluorescence", "descriptor_ui": "D013050", "major_topic": false }, { "descriptor": "Uroporphyrins", "descriptor_ui": "D014578", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Sep 19", "date_precision": "day", "issue": "18", "normalized_date": "2021-09-19", "pages": "10121", "proceedings_title": null, "publisher": "", "title": "International journal of molecular sciences", "volume": "22", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Accumulation of Uroporphyrin I in Necrotic Tissues of Squamous Cell Carcinoma after Administration of 5-Aminolevulinic Acid.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Disruption of mitochondrial morphology occurs during various diseases, but the biological significance is not entirely clear. Here, we describe a detailed step-by-step protocol for a chemically inducible dimerization system-based synthetic protein device, termed inducible counter mitochondrial morphology. This system allows artificial manipulation of mitochondrial morphology on a timescale of minutes in living mammalian cells. We also describe an AI-assisted imaging processing approach. For complete details on the use and execution of this protocol, please refer to Miyamoto et al., 2021.", "classifications": [ { "id": "JPMJCR1927", "label": "JPMJCR1927", "researcher": "Yuichi Wakamoto", "type": "grant" }, { "id": "Miyamoto", "label": "Group Miyamoto", "parent": "Wakamoto", "type": "group" }, { "id": "Wakamoto", "label": "Group Wakamoto", "parent": "Wakamoto", "type": "group" }, { "id": "Wakamoto", "label": "Team Wakamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Takafumi", "last_name": "Miyamoto", "name": null }, { "creator_type": "author", "first_name": "Song-Iee", "last_name": "Han", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Shimano", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.xpro.2021.100721" }, "pmcid": { "normalized": "PMC8353406" }, "pmid": { "normalized": "34401787" } }, "mesh": [ { "descriptor": "Dimerization", "descriptor_ui": "D019281", "major_topic": false }, { "descriptor": "Genetic Engineering", "descriptor_ui": "D005818", "major_topic": false }, { "descriptor": "HeLa Cells", "descriptor_ui": "D006367", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mitochondria", "descriptor_ui": "D008928", "major_topic": false }, { "descriptor": "Organelle Shape", "descriptor_ui": "D053140", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Sep 17", "date_precision": "day", "issue": "3", "normalized_date": "2021-09-17", "pages": "100721", "proceedings_title": null, "publisher": "", "title": "STAR protocols", "volume": "2", "year": 2021 }, "ssbd": { "database": [ "ssbd-database-000239" ], "repository": [ "ssbd-repos-000239" ] }, "title": "Protocol for rapid manipulation of mitochondrial morphology in living cells using inducible counter mitochondrial morphology (iCMM).", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Proper organ development often requires nuclei to move to a specific position within the cell. To determine how nuclear positioning affects left-right (LR) development in the Drosophila anterior midgut (AMG), we developed a surface-modeling method to measure and describe nuclear behavior at stages 13-14, captured in three-dimensional time-lapse movies. We describe the distinctive positioning and a novel collective nuclear behavior by which nuclei align LR symmetrically along the anterior-posterior axis in the visceral muscles that overlie the midgut and are responsible for the LR-asymmetric development of this organ. Wnt4 signaling is crucial for the collective behavior and proper positioning of the nuclei, as are myosin II and the LINC complex, without which the nuclei fail to align LR symmetrically. The LR-symmetric positioning of the nuclei is important for the subsequent LR-asymmetric development of the AMG. We propose that the bilaterally symmetrical positioning of these nuclei may be mechanically coupled with subsequent LR-asymmetric morphogenesis.", "classifications": [ { "id": "Eiraku", "label": "Group Eiraku", "parent": "Eiraku", "type": "group" }, { "id": "Eiraku", "label": "Team Eiraku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Dongsun", "last_name": "Shin", "name": null }, { "creator_type": "author", "first_name": "Mitsutoshi", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Yoshitaka", "last_name": "Morishita", "name": null }, { "creator_type": "author", "first_name": "Mototsugu", "last_name": "Eiraku", "name": null }, { "creator_type": "author", "first_name": "Tomoko", "last_name": "Yamakawa", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Sasamura", "name": null }, { "creator_type": "author", "first_name": "Masakazu", "last_name": "Akiyama", "name": null }, { "creator_type": "author", "first_name": "Mikiko", "last_name": "Inaki", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Matsuno", "name": null } ], "identifiers": { "doi": { "normalized": "10.1242/dev.198507" }, "pmcid": { "normalized": "PMC8126412" }, "pmid": { "normalized": "34097729" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Body Patterning", "descriptor_ui": "D019521", "major_topic": false }, { "descriptor": "Cell Nucleus", "descriptor_ui": "D002467", "major_topic": false }, { "descriptor": "Digestive System", "descriptor_ui": "D004064", "major_topic": false }, { "descriptor": "Drosophila", "descriptor_ui": "D004330", "major_topic": false }, { "descriptor": "Drosophila Proteins", "descriptor_ui": "D029721", "major_topic": false }, { "descriptor": "Gene Expression Regulation, Developmental", "descriptor_ui": "D018507", "major_topic": false }, { "descriptor": "Morphogenesis", "descriptor_ui": "D009024", "major_topic": false }, { "descriptor": "Muscles", "descriptor_ui": "D009132", "major_topic": false }, { "descriptor": "Myosin Type II", "descriptor_ui": "D024462", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Sep 15", "date_precision": "day", "issue": "18", "normalized_date": "2021-09-15", "pages": "dev198507", "proceedings_title": null, "publisher": "", "title": "Development (Cambridge, England)", "volume": "148", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Collective nuclear behavior shapes bilateral nuclear symmetry for subsequent left-right asymmetric morphogenesis in Drosophila.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Patients with type 2 diabetes treated with Sodium glucose transporter 2 (SGLT2) inhibitors show reduced mortality and hospitalization for heart failure (HF). SGLT2 inhibitors are considered to activate multiple cardioprotective pathways; however, underlying mechanisms are not fully described. This study aimed to elucidate the underlying mechanisms of the beneficial effects of SGLT2 inhibitors on the failing heart. We generated a left ventricular (LV) pressure overload model in C57BL/6NCrSlc mice by transverse aortic constriction (TAC) and examined the effects of empagliflozin (EMPA) in this model. We conducted metabolome and transcriptome analyses and histological and physiological examinations. EMPA administration ameliorated pressure overload-induced systolic dysfunction. Metabolomic studies showed that EMPA increased citrulline levels in cardiac tissue and reduced levels of arginine, indicating enhanced metabolism from arginine to citrulline and nitric oxide (NO). Transcriptome suggested possible involvement of the insulin/AKT pathway that could activate NO production through phosphorylation of endothelial NO synthase (eNOS). Histological examination of the mice showed capillary rarefaction and endothelial apoptosis after TAC, both of which were significantly improved by EMPA treatment. This improvement was associated with enhanced expression phospho-eNOS and NO production in cardiac endothelial cells. NOS inhibition attenuated these cardioprotective effects of EMPA. The in vitro studies showed that catecholamine-induced endothelial apoptosis was inhibited by NO, arginine, or AKT activator. EMPA activates the AKT/eNOS/NO pathway, which helps to suppress endothelial apoptosis, maintain capillarization and improve systolic dysfunction during LV pressure overload.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Masaaki", "last_name": "Nakao", "name": null }, { "creator_type": "author", "first_name": "Ippei", "last_name": "Shimizu", "name": null }, { "creator_type": "author", "first_name": "Goro", "last_name": "Katsuumi", "name": null }, { "creator_type": "author", "first_name": "Yohko", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Masayoshi", "last_name": "Suda", "name": null }, { "creator_type": "author", "first_name": "Yuka", "last_name": "Hayashi", "name": null }, { "creator_type": "author", "first_name": "Ryutaro", "last_name": "Ikegami", "name": null }, { "creator_type": "author", "first_name": "Yung Ting", "last_name": "Hsiao", "name": null }, { "creator_type": "author", "first_name": "Shujiro", "last_name": "Okuda", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Tohru", "last_name": "Minamino", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41598-021-97787-2" }, "pmcid": { "normalized": "PMC8443662" }, "pmid": { "normalized": "34526601" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Benzhydryl Compounds", "descriptor_ui": "D001559", "major_topic": false }, { "descriptor": "Biomarkers", "descriptor_ui": "D015415", "major_topic": false }, { "descriptor": "Blood Pressure", "descriptor_ui": "D001794", "major_topic": false }, { "descriptor": "Cardiotonic Agents", "descriptor_ui": "D002316", "major_topic": false }, { "descriptor": "Disease Management", "descriptor_ui": "D019468", "major_topic": false }, { "descriptor": "Disease Models, Animal", "descriptor_ui": "D004195", "major_topic": false }, { "descriptor": "Gene Expression Profiling", "descriptor_ui": "D020869", "major_topic": false }, { "descriptor": "Glucosides", "descriptor_ui": "D005960", "major_topic": false }, { "descriptor": "Heart Failure", "descriptor_ui": "D006333", "major_topic": false }, { "descriptor": "Immunohistochemistry", "descriptor_ui": "D007150", "major_topic": false }, { "descriptor": "Metabolome", "descriptor_ui": "D055442", "major_topic": false }, { "descriptor": "Metabolomics", "descriptor_ui": "D055432", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Microcirculation", "descriptor_ui": "D008833", "major_topic": false }, { "descriptor": "Models, Biological", "descriptor_ui": "D008954", "major_topic": false }, { "descriptor": "Norepinephrine", "descriptor_ui": "D009638", "major_topic": false }, { "descriptor": "Sodium-Glucose Transporter 2 Inhibitors", "descriptor_ui": "D000077203", "major_topic": false }, { "descriptor": "Ventricular Dysfunction, Left", "descriptor_ui": "D018487", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Sep 15", "date_precision": "day", "issue": "1", "normalized_date": "2021-09-15", "pages": "18384", "proceedings_title": null, "publisher": "", "title": "Scientific reports", "volume": "11", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Empagliflozin maintains capillarization and improves cardiac function in a murine model of left ventricular pressure overload.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Symmetry in the arrangement of body parts is a distinctive phylogenetic feature of animals. Cnidarians show both bilateral and radial symmetries in their internal organs, such as gastric pouches and muscles. However, how different symmetries appear during the developmental process remains unknown. Here, we report intraspecific variations in the symmetric arrangement of gastric pouches, muscles, and siphonoglyphs, the Anthozoan-specific organ that drives water into the organism, in D. lineata (Diadumenidae, Actiniaria). We found that the positional arrangement of the internal organs was apparently constrained to either biradial or bilateral symmetries depending on the number of siphonoglyphs. Based on the morphological observations, a mathematical model of internal organ positioning was employed to predict the developmental backgrounds responsible for the biradial and bilateral symmetries. In the model, we assumed that the specification of gastric pouches is orchestrated by lateral inhibition and activation, which results in different symmetries depending on the number of siphonoglyphs. Thus, we propose that a common developmental program can generate either bilateral or biradial symmetries depending on the number of siphonoglyphs formed in the early developmental stages.", "classifications": [ { "id": "Fujimoto", "label": "Group Fujimoto", "parent": "Ueda", "type": "group" }, { "id": "Ueda", "label": "Team Ueda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Safiye E.", "last_name": "Sarper", "name": null }, { "creator_type": "author", "first_name": "Tamami", "last_name": "Hirai", "name": null }, { "creator_type": "author", "first_name": "Take", "last_name": "Matsuyama", "name": null }, { "creator_type": "author", "first_name": "Shigeru", "last_name": "Kuratani", "name": null }, { "creator_type": "author", "first_name": "Koichi", "last_name": "Fujimoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1186/s40851-021-00180-0" }, "pmcid": { "normalized": "PMC8419960" }, "pmid": { "normalized": "34488893" } }, "mesh": [], "publication": { "conference_name": null, "date": "2021 Sep 6", "date_precision": "day", "issue": "1", "normalized_date": "2021-09-06", "pages": "12", "proceedings_title": null, "publisher": "", "title": "Zoological letters", "volume": "7", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Polymorphism in the symmetries of gastric pouch arrangements in the sea anemone D. lineata.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The coronavirus disease 2019 (COVID-19) pandemic began at the end of December 2019, giving rise to a high rate of infections and causing COVID-19-associated deaths worldwide. It was first reported in Wuhan, China, and since then, not only global leaders, organizations, and pharmaceutical/biotech companies, but also researchers, have directed their efforts toward overcoming this threat. The use of artificial intelligence (AI) has recently surged internationally and has been applied to diverse aspects of many problems. The benefits of using AI are now widely accepted, and many studies have shown great success in medical research on tasks, such as the classification, detection, and prediction of disease, or even patient outcome. In fact, AI technology has been actively employed in various ways in COVID-19 research, and several clinical applications of AI-equipped medical devices for the diagnosis of COVID-19 have already been reported. Hence, in this review, we summarize the latest studies that focus on medical imaging analysis, drug discovery, and therapeutics such as vaccine development and public health decision-making using AI. This survey clarifies the advantages of using AI in the fight against COVID-19 and provides future directions for tackling the COVID-19 pandemic using AI techniques.", "classifications": [ { "id": "Hamamoto", "label": "Group Hamamoto", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Ken", "last_name": "Asada", "name": null }, { "creator_type": "author", "first_name": "Masaaki", "last_name": "Komatsu", "name": null }, { "creator_type": "author", "first_name": "Ryo", "last_name": "Shimoyama", "name": null }, { "creator_type": "author", "first_name": "Ken", "last_name": "Takasawa", "name": null }, { "creator_type": "author", "first_name": "Norio", "last_name": "Shinkai", "name": null }, { "creator_type": "author", "first_name": "Akira", "last_name": "Sakai", "name": null }, { "creator_type": "author", "first_name": "Amina", "last_name": "Bolatkan", "name": null }, { "creator_type": "author", "first_name": "Masayoshi", "last_name": "Yamada", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Hidenori", "last_name": "Machino", "name": null }, { "creator_type": "author", "first_name": "Kazuma", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Syuzo", "last_name": "Kaneko", "name": null }, { "creator_type": "author", "first_name": "Ryuji", "last_name": "Hamamoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.3390/jpm11090886" }, "pmcid": { "normalized": "PMC8471764" }, "pmid": { "normalized": "34575663" } }, "mesh": [], "publication": { "conference_name": null, "date": "2021 Sep 4", "date_precision": "day", "issue": "9", "normalized_date": "2021-09-04", "pages": "886", "proceedings_title": null, "publisher": "", "title": "Journal of personalized medicine", "volume": "11", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Application of Artificial Intelligence in COVID-19 Diagnosis and Therapeutics.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Mesoionic carbene-stabilized borenium ions efficiently reduce substituted pyridines to piperidines in the presence of a hydrosilane and a hydrogen atmosphere. Control experiments and deuterium labeling studies demonstrate reversible hydrosilylation of the pyridine, enabling full reduction of the N-heterocycle under milder conditions. The silane is a critical reaction component to prevent adduct formation between the piperidine product and the borenium catalyst.", "classifications": [ { "id": "Nanbo", "label": "Group Nanbo", "parent": "Tsuchiya", "type": "group" }, { "id": "Tsuchiya", "label": "Team Tsuchiya", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Joshua J.", "last_name": "Clarke", "name": null }, { "creator_type": "author", "first_name": "Yuuki", "last_name": "Maekawa", "name": null }, { "creator_type": "author", "first_name": "Masakazu", "last_name": "Nambo", "name": null }, { "creator_type": "author", "first_name": "Cathleen M.", "last_name": "Crudden", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/acs.orglett.1c01892" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "34383490" } }, "mesh": [], "publication": { "conference_name": null, "date": "2021 Sep 3", "date_precision": "day", "issue": "17", "normalized_date": "2021-09-03", "pages": "6617-6621", "proceedings_title": null, "publisher": "", "title": "Organic letters", "volume": "23", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Borenium-Catalyzed Reduction of Pyridines through the Combined Action of Hydrogen and Hydrosilane.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "In 2019, a novel severe acute respiratory syndrome called coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was reported and was declared a pandemic by the World Health Organization (WHO) in March 2020. With the advancing development of COVID-19 vaccines and their administration globally, it is expected that COVID-19 will converge in the future; however, the situation remains unpredictable because of a series of reports regarding SARS-CoV-2 variants. Currently, there are still few specific effective treatments for COVID-19, as many unanswered questions remain regarding the pathogenic mechanism of COVID-19. Continued elucidation of COVID-19 pathogenic mechanisms is a matter of global importance. In this regard, recent reports have suggested that epigenetics plays an important role; for instance, the expression of angiotensin I converting enzyme 2 (ACE2) receptor, an important factor in human infection with SARS-CoV-2, is epigenetically regulated; further, DNA methylation status is reported to be unique to patients with COVID-19. In this review, we focus on epigenetic mechanisms to provide a new molecular framework for elucidating the pathogenesis of SARS-CoV-2 infection in humans and of COVID-19, along with the possibility of new diagnostic and therapeutic strategies.", "classifications": [ { "id": "Hamamoto", "label": "Group Hamamoto", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Syuzo", "last_name": "Kaneko", "name": null }, { "creator_type": "author", "first_name": "Ken", "last_name": "Takasawa", "name": null }, { "creator_type": "author", "first_name": "Ken", "last_name": "Asada", "name": null }, { "creator_type": "author", "first_name": "Norio", "last_name": "Shinkai", "name": null }, { "creator_type": "author", "first_name": "Amina", "last_name": "Bolatkan", "name": null }, { "creator_type": "author", "first_name": "Masayoshi", "last_name": "Yamada", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Hidenori", "last_name": "Machino", "name": null }, { "creator_type": "author", "first_name": "Kazuma", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Masaaki", "last_name": "Komatsu", "name": null }, { "creator_type": "author", "first_name": "Ryuji", "last_name": "Hamamoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.3390/biomedicines9091142" }, "pmcid": { "normalized": "PMC8466119" }, "pmid": { "normalized": "34572329" } }, "mesh": [], "publication": { "conference_name": null, "date": "2021 Sep 2", "date_precision": "day", "issue": "9", "normalized_date": "2021-09-02", "pages": "1142", "proceedings_title": null, "publisher": "", "title": "Biomedicines", "volume": "9", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Epigenetic Mechanisms Underlying COVID-19 Pathogenesis.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Mitochondrial electron transport chain complex I (ETCC1) is the essential core of cancer metabolism, yet potent ETCC1 inhibitors capable of safely suppressing tumor growth and metastasis in vivo are limited. From a plant extract screening, we identified petasin (PT) as a highly potent ETCC1 inhibitor with a chemical structure distinct from conventional inhibitors. PT had at least 1700 times higher activity than that of metformin or phenformin and induced cytotoxicity against a broad spectrum of tumor types. PT administration also induced prominent growth inhibition in multiple syngeneic and xenograft mouse models in vivo. Despite its higher potency, it showed no apparent toxicity toward nontumor cells and normal organs. Also, treatment with PT attenuated cellular motility and focal adhesion in vitro as well as lung metastasis in vivo. Metabolome and proteome analyses revealed that PT severely depleted the level of aspartate, disrupted tumor-associated metabolism of nucleotide synthesis and glycosylation, and downregulated major oncoproteins associated with proliferation and metastasis. These findings indicate the promising potential of PT as a potent ETCC1 inhibitor to target the metabolic vulnerability of tumor cells.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Kazuki", "last_name": "Heishima", "name": null }, { "creator_type": "author", "first_name": "Nobuhiko", "last_name": "Sugito", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Masashi", "last_name": "Nishikawa", "name": null }, { "creator_type": "author", "first_name": "Yuko", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Ryo", "last_name": "Honda", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Kuranaga", "name": null }, { "creator_type": "author", "first_name": "Hiroki", "last_name": "Sakai", "name": null }, { "creator_type": "author", "first_name": "Ryo", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Takayuki", "last_name": "Nakagawa", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Ueda", "name": null }, { "creator_type": "author", "first_name": "Yukihiro", "last_name": "Akao", "name": null } ], "identifiers": { "doi": { "normalized": "10.1172/jci139933" }, "pmcid": { "normalized": "PMC8409585" }, "pmid": { "normalized": "34623325" } }, "mesh": [ { "descriptor": "Adenosine Triphosphate", "descriptor_ui": "D000255", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Antineoplastic Agents, Phytogenic", "descriptor_ui": "D000972", "major_topic": false }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Electron Transport Complex I", "descriptor_ui": "D042967", "major_topic": false }, { "descriptor": "Endoplasmic Reticulum Stress", "descriptor_ui": "D059865", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Lung Neoplasms", "descriptor_ui": "D008175", "major_topic": false }, { "descriptor": "Metabolome", "descriptor_ui": "D055442", "major_topic": false }, { "descriptor": "Metformin", "descriptor_ui": "D008687", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred BALB C", "descriptor_ui": "D008807", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Nude", "descriptor_ui": "D008819", "major_topic": false }, { "descriptor": "Neoplasm Metastasis", "descriptor_ui": "D009362", "major_topic": false }, { "descriptor": "Neoplasms, Experimental", "descriptor_ui": "D009374", "major_topic": false }, { "descriptor": "Petasites", "descriptor_ui": "D036901", "major_topic": false }, { "descriptor": "Phenformin", "descriptor_ui": "D010629", "major_topic": false }, { "descriptor": "Sesquiterpenes", "descriptor_ui": "D012717", "major_topic": false }, { "descriptor": "Unfolded Protein Response", "descriptor_ui": "D056811", "major_topic": false }, { "descriptor": "Xenograft Model Antitumor Assays", "descriptor_ui": "D023041", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Sep 1", "date_precision": "day", "issue": "17", "normalized_date": "2021-09-01", "pages": "", "proceedings_title": null, "publisher": "", "title": "The Journal of clinical investigation", "volume": "131", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Petasin potently inhibits mitochondrial complex I-based metabolism that supports tumor growth and metastasis.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The PI3K/Akt/mTOR pathway has been well known to interact with the estrogen receptor (ER)-pathway and to be also frequently upregulated in aromatase inhibitor (AI)-resistant breast cancer patients. Intracellular levels of free amino acids, especially leucine, regulate the mammalian target of rapamycin complex 1 (mTORC1) activation. L-type amino acid transporters such as LAT1 and LAT3 are associated with the uptake of essential amino acids. LAT1 expression could mediate leucine uptake, mTORC1 signaling, and cell proliferation. Therefore, in this study, we explored amino acid metabolism, including LAT1, in breast cancer and clarified the potential roles of LAT1 in the development of therapeutic resistance and the eventual clinical outcome of the patients. We evaluated LAT1 and LAT3 expression before and after neoadjuvant hormone therapy (NAH) and examined LAT1 function and expression in estrogen deprivation-resistant (EDR) breast carcinoma cell lines. Tumors tended to be in advanced stages in the cases whose LAT1 expression was high. LAT1 expression in the EDR cell lines was upregulated. JPH203, a selective LAT1 inhibitor, demonstrated inhibitory effects on cell proliferation in EDR cells. Hormone therapy changed the tumor microenvironment and resulted in metabolic reprogramming through inducing LAT1 expression. LAT1 expression then mediated leucine uptake, enhanced mTORC1 signaling, and eventually resulted in AI resistance. Therefore, LAT1 could be the potential therapeutic target in AI-resistant breast cancer patients.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Haruhiko", "last_name": "Shindo", "name": null }, { "creator_type": "author", "first_name": "Narumi", "last_name": "Harada-Shoji", "name": null }, { "creator_type": "author", "first_name": "Akiko", "last_name": "Ebata", "name": null }, { "creator_type": "author", "first_name": "Miku", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Minoru", "last_name": "Miyashita", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Tada", "name": null }, { "creator_type": "author", "first_name": "Masaaki", "last_name": "Kawai", "name": null }, { "creator_type": "author", "first_name": "Shinkichi", "last_name": "Kosaka", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Onuki", "name": null }, { "creator_type": "author", "first_name": "Shin", "last_name": "Usami", "name": null }, { "creator_type": "author", "first_name": "Shozo", "last_name": "Furumoto", "name": null }, { "creator_type": "author", "first_name": "Shinichi", "last_name": "Hayashi", "name": null }, { "creator_type": "author", "first_name": "Takaaki", "last_name": "Abe", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Takanori", "last_name": "Ishida", "name": null }, { "creator_type": "author", "first_name": "Hironobu", "last_name": "Sasano", "name": null } ], "identifiers": { "doi": { "normalized": "10.3390/cancers13174375" }, "pmcid": { "normalized": "PMC8431153" }, "pmid": { "normalized": "34503187" } }, "mesh": [], "publication": { "conference_name": null, "date": "2021 Aug 30", "date_precision": "day", "issue": "17", "normalized_date": "2021-08-30", "pages": "", "proceedings_title": null, "publisher": "", "title": "Cancers", "volume": "13", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Targeting Amino Acid Metabolic Reprogramming via L-Type Amino Acid Transporter 1 (LAT1) for Endocrine-Resistant Breast Cancer.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Polyamine metabolites provide pathophysiological information on disease or therapeutic efficacy, yet rapid screening methods for these biomarkers are lacking. Here, we developed high-throughput polyamine metabolite profiling based on multisegment injection capillary electrophoresis triple quadrupole tandem mass spectrometry (MSI-CE-MS/MS), which allows sequential 40-sample injection followed by electrophoretic separation and specific mass detection. To achieve consecutive analysis of polyamine samples, 1 M formic acid was used as the background electrolyte (BGE). The BGE spacer volume had an apparent effect on peak resolution among samples, and 20 nL was selected as the optimal volume. The use of polyamine isotopomers as the internal standard enabled the correction of matrix effects in MS detection. This method is sensitive, selective and quantitative, and its utility was demonstrated by screening polyamines in 359 salivary samples within 360 min, resulting in discrimination of colorectal cancer patients from noncancer controls.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Kaori", "last_name": "Igarashi", "name": null }, { "creator_type": "author", "first_name": "Sana", "last_name": "Ota", "name": null }, { "creator_type": "author", "first_name": "Miku", "last_name": "Kaneko", "name": null }, { "creator_type": "author", "first_name": "Akiyoshi", "last_name": "Hirayama", "name": null }, { "creator_type": "author", "first_name": "Masanobu", "last_name": "Enomoto", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Katumata", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Sugimoto", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.chroma.2021.462355" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "34233246" } }, "mesh": [ { "descriptor": "Biomarkers, Tumor", "descriptor_ui": "D014408", "major_topic": false }, { "descriptor": "Colorectal Neoplasms", "descriptor_ui": "D015179", "major_topic": false }, { "descriptor": "Electrophoresis, Capillary", "descriptor_ui": "D019075", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Polyamines", "descriptor_ui": "D011073", "major_topic": false }, { "descriptor": "Saliva", "descriptor_ui": "D012463", "major_topic": false }, { "descriptor": "Tandem Mass Spectrometry", "descriptor_ui": "D053719", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Aug 30", "date_precision": "day", "issue": "", "normalized_date": "2021-08-30", "pages": "462355", "proceedings_title": null, "publisher": "", "title": "Journal of chromatography. A", "volume": "1652", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "High-throughput screening of salivary polyamine markers for discrimination of colorectal cancer by multisegment injection capillary electrophoresis tandem mass spectrometry.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "An effective combination of multi-omic datasets can enhance our understanding of complex biological phenomena. To build a context-dependent network with multiple omic layers, i.e., a trans-omic network, we perform phosphoproteomics, transcriptomics, proteomics, and metabolomics of murine liver for 4 h after insulin administration and integrate the resulting time series. Structural characteristics and dynamic nature of the network are analyzed to elucidate the impact of insulin. Early and prominent changes in protein phosphorylation and persistent and asynchronous changes in mRNA and protein levels through non-transcriptional mechanisms indicate enhanced crosstalk between phosphorylation-mediated signaling and protein expression regulation. Metabolic response shows different temporal regulation with transient increases at early time points across categories and enhanced response in the amino acid and nucleotide categories at later time points as a result of process convergence. This extensive and dynamic view of the trans-omic network elucidates prominent regulatory mechanisms that drive insulin responses through intricate interlayer coordination.", "classifications": [ { "id": "Kuroda", "label": "Group Kuroda", "parent": "Kuroda", "type": "group" }, { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Fumiko", "last_name": "Matsuzaki", "name": null }, { "creator_type": "author", "first_name": "Shinsuke", "last_name": "Uda", "name": null }, { "creator_type": "author", "first_name": "Yukiyo", "last_name": "Yamauchi", "name": null }, { "creator_type": "author", "first_name": "Masaki", "last_name": "Matsumoto", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Kazumitsu", "last_name": "Maehara", "name": null }, { "creator_type": "author", "first_name": "Yasuyuki", "last_name": "Ohkawa", "name": null }, { "creator_type": "author", "first_name": "Keiichi I.", "last_name": "Nakayama", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Kuroda", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Kubota", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.celrep.2021.109569" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "34433063" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Gene Expression Regulation", "descriptor_ui": "D005786", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Insulin", "descriptor_ui": "D007328", "major_topic": false }, { "descriptor": "Liver", "descriptor_ui": "D008099", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Metabolomics", "descriptor_ui": "D055432", "major_topic": true }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Proteomics", "descriptor_ui": "D040901", "major_topic": true }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Aug 24", "date_precision": "day", "issue": "8", "normalized_date": "2021-08-24", "pages": "109569", "proceedings_title": null, "publisher": "", "title": "Cell reports", "volume": "36", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "An extensive and dynamic trans-omic network illustrating prominent regulatory mechanisms in response to insulin in the liver.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Engineered synthetic biomolecular devices that integrate elaborate information processing and precisely regulate living cell behavior have potential in various applications. Although devices that directly regulate key biomolecules constituting inherent biological systems exist, no devices have been developed to control intracellular membrane architecture, contributing to the spatiotemporal functions of these biomolecules. This study developed a synthetic biomolecular device, termed inducible counter mitochondrial morphology (iCMM), to manipulate mitochondrial morphology, an emerging informative property for understanding physiopathological cellular behaviors, on a minute timescale by using a chemically inducible dimerization system. Using iCMM, we determined cellular changes by altering mitochondrial morphology in an unprecedented manner. This approach serves as a platform for developing more sophisticated synthetic biomolecular devices to regulate biological systems by extending manipulation targets from conventional biomolecules to mitochondria. Furthermore, iCMM might serve as a tool for uncovering the biological significance of mitochondrial morphology in various physiopathological cellular processes.", "classifications": [ { "id": "JPMJCR1927", "label": "JPMJCR1927", "researcher": "Yuichi Wakamoto", "type": "grant" }, { "id": "Miyamoto", "label": "Group Miyamoto", "parent": "Wakamoto", "type": "group" }, { "id": "Wakamoto", "label": "Group Wakamoto", "parent": "Wakamoto", "type": "group" }, { "id": "Wakamoto", "label": "Team Wakamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Takafumi", "last_name": "Miyamoto", "name": null }, { "creator_type": "author", "first_name": "Hideki", "last_name": "Uosaki", "name": null }, { "creator_type": "author", "first_name": "Yuhei", "last_name": "Mizunoe", "name": null }, { "creator_type": "author", "first_name": "Song-Iee", "last_name": "Han", "name": null }, { "creator_type": "author", "first_name": "Satoi", "last_name": "Goto", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Yamanaka", "name": null }, { "creator_type": "author", "first_name": "Masato", "last_name": "Masuda", "name": null }, { "creator_type": "author", "first_name": "Yosuke", "last_name": "Yoneyama", "name": null }, { "creator_type": "author", "first_name": "Hideki", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Naoko", "last_name": "Hattori", "name": null }, { "creator_type": "author", "first_name": "Yoshinori", "last_name": "Takeuchi", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Ohno", "name": null }, { "creator_type": "author", "first_name": "Motohiro", "last_name": "Sekiya", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Matsuzaka", "name": null }, { "creator_type": "author", "first_name": "Fumihiko", "last_name": "Hakuno", "name": null }, { "creator_type": "author", "first_name": "Shin-Ichiro", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Naoya", "last_name": "Yahagi", "name": null }, { "creator_type": "author", "first_name": "Koichi", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Shimano", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.crmeth.2021.100052" }, "pmcid": { "normalized": "PMC9017203" }, "pmid": { "normalized": "35475143" } }, "mesh": [ { "descriptor": "Mitochondria", "descriptor_ui": "D008928", "major_topic": true }, { "descriptor": "Synthetic Biology", "descriptor_ui": "D058615", "major_topic": true } ], "publication": { "conference_name": null, "date": "2021 Aug 23", "date_precision": "day", "issue": "4", "normalized_date": "2021-08-23", "pages": "100052", "proceedings_title": null, "publisher": "", "title": "Cell reports methods", "volume": "1", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Rapid manipulation of mitochondrial morphology in a living cell with iCMM.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The ‘open’ and ‘compact’ regions of chromatin are considered to be regions of active and silent transcription, respectively. However, individual genes produce transcripts at different levels, suggesting that transcription output does not depend on the simple open-compact conversion of chromatin, but on structural variations in chromatin itself, which so far have remained elusive. In this study, weakly crosslinked chromatin was subjected to sedimentation velocity centrifugation, which fractionated the chromatin according to its degree of compaction. Open chromatin remained in upper fractions, while compact chromatin sedimented to lower fractions depending on the level of nucleosome assembly. Although nucleosomes were evenly detected in all fractions, histone H1 was more highly enriched in the lower fractions. H1 was found to self-associate and crosslinked to histone H3, suggesting that H1 bound to H3 interacts with another H1 in an adjacent nucleosome to form compact chromatin. Genome-wide analyses revealed that nearly the entire genome consists of compact chromatin without differences in compaction between repeat and non-repeat sequences; however, active transcription start sites (TSSs) were rarely found in compact chromatin. Considering the inverse correlation between chromatin compaction and RNA polymerase binding at TSSs, it appears that local states of chromatin compaction determine transcription levels.", "classifications": [ { "id": "Nikaido", "label": "Group Nikaido", "parent": "Fujiwara", "type": "group" }, { "id": "Fujiwara", "label": "Team Fujiwara", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Satoru", "last_name": "Ishihara", "name": null }, { "creator_type": "author", "first_name": "Yohei", "last_name": "Sasagawa", "name": null }, { "creator_type": "author", "first_name": "Takeru", "last_name": "Kameda", "name": null }, { "creator_type": "author", "first_name": "Hayato", "last_name": "Yamashita", "name": null }, { "creator_type": "author", "first_name": "Mana", "last_name": "Umeda", "name": null }, { "creator_type": "author", "first_name": "Naoe", "last_name": "Kotomura", "name": null }, { "creator_type": "author", "first_name": "Masayuki", "last_name": "Abe", "name": null }, { "creator_type": "author", "first_name": "Yohei", "last_name": "Shimono", "name": null }, { "creator_type": "author", "first_name": "Itoshi", "last_name": "Nikaido", "name": null } ], "identifiers": { "doi": { "normalized": "10.1093/nar/gkab587" }, "pmcid": { "normalized": null }, "pmid": { "normalized": null } }, "mesh": [], "publication": { "conference_name": null, "date": "2021-08-20", "date_precision": "day", "issue": "14", "normalized_date": "2021-08-20", "pages": "8007-8023", "proceedings_title": null, "publisher": "", "title": "Nucleic Acids Research", "volume": "49", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Local states of chromatin compaction at transcription start sites control transcription levels", "url": "https://doi.org/10.1093/nar/gkab587", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Patient-derived cells and xenografts retain the biological characteristics of clinical cancers and are instrumental in gaining a better understanding of the chemoresistance of cancer cells. Here, we have established a panel of patient-derived spheroids from clinical materials of ovarian cancer. Systematic evaluation using therapeutic agents indicated that sensitivity to platinum-based compounds significantly varied among the spheroids. To understand the molecular basis of drug sensitivity, we performed integrative analyses combining chemoresistance data and gene expression profiling of the ovarian cancer patient-derived spheroids. Correlation analyses revealed that cisplatin resistance was significantly associated with elevated levels of glucose-6-phosphate dehydrogenase (G6PD) and glutathione-producing redox enzymes. Accordingly, cisplatin-resistant spheroids established in vitro showed elevated levels of G6PD and active glutathione. Moreover, treatment with a G6PD inhibitor in combination with cisplatin suppressed spheroid proliferation in vitro and largely eradicated peritoneal metastasis in mouse xenograft models. Furthermore, G6PD expression was elevated during carcinogenesis and associated with poor prognosis. Thus, the combination of gene expression data and chemosensitivity revealed the essential roles of G6PD-driven redox metabolism in cisplatin resistance, underscoring the significance of an integrative approach using patient-derived cells.", "classifications": [ { "id": "Okamoto", "label": "Group Okamoto", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Kaoru", "last_name": "Yamawaki", "name": null }, { "creator_type": "author", "first_name": "Yutaro", "last_name": "Mori", "name": null }, { "creator_type": "author", "first_name": "Hiroaki", "last_name": "Sakai", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Kanda", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Shiokawa", "name": null }, { "creator_type": "author", "first_name": "Haruka", "last_name": "Ueda", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Ishiguro", "name": null }, { "creator_type": "author", "first_name": "Kosuke", "last_name": "Yoshihara", "name": null }, { "creator_type": "author", "first_name": "Kazunori", "last_name": "Nagasaka", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Onda", "name": null }, { "creator_type": "author", "first_name": "Tomoyasu", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Tadashi", "last_name": "Kondo", "name": null }, { "creator_type": "author", "first_name": "Takayuki", "last_name": "Enomoto", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Okamoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.canlet.2021.08.018" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "34419499" } }, "mesh": [], "publication": { "conference_name": null, "date": "2021 Aug 19", "date_precision": "day", "issue": "", "normalized_date": "2021-08-19", "pages": "29-38", "proceedings_title": null, "publisher": "", "title": "Cancer letters", "volume": "521", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Integrative analyses of gene expression and chemosensitivity of patient-derived ovarian cancer spheroids link G6PD-driven redox metabolism to cisplatin chemoresistance.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The Western pattern diet is rich not only in fat and calories but also in phosphate. The negative effects of excessive fat and calorie intake on health are widely known, but the potential harms of excessive phosphate intake are poorly recognized. Here, we show the mechanism by which dietary phosphate damages the kidney. When phosphate intake was excessive relative to the number of functioning nephrons, circulating levels of FGF23, a hormone that increases the excretion of phosphate per nephron, were increased to maintain phosphate homeostasis. FGF23 suppressed phosphate reabsorption in renal tubules and thus raised the phosphate concentration in the tubule fluid. Once it exceeded a threshold, microscopic particles containing calcium phosphate crystals appeared in the tubule lumen, which damaged tubule cells through binding to the TLR4 expressed on them. Persistent tubule damage induced interstitial fibrosis, reduced the number of nephrons, and further boosted FGF23 to trigger a deterioration spiral leading to progressive nephron loss. In humans, the progression of chronic kidney disease (CKD) ensued when serum FGF23 levels exceeded 53 pg/mL. The present study identified calcium phosphate particles in the renal tubular fluid as an effective therapeutic target to decelerate nephron loss during the course of aging and CKD progression.", "classifications": [ { "id": "Kuchimaru", "label": "Group Kuchimaru", "parent": "Shintaku", "type": "group" }, { "id": "Shintaku", "label": "Team Shintaku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Kazuhiro", "last_name": "Shiizaki", "name": null }, { "creator_type": "author", "first_name": "Asako", "last_name": "Tsubouchi", "name": null }, { "creator_type": "author", "first_name": "Yutaka", "last_name": "Miura", "name": null }, { "creator_type": "author", "first_name": "Kinya", "last_name": "Seo", "name": null }, { "creator_type": "author", "first_name": "Takahiro", "last_name": "Kuchimaru", "name": null }, { "creator_type": "author", "first_name": "Hirosaka", "last_name": "Hayashi", "name": null }, { "creator_type": "author", "first_name": "Yoshitaka", "last_name": "Iwazu", "name": null }, { "creator_type": "author", "first_name": "Marina", "last_name": "Miura", "name": null }, { "creator_type": "author", "first_name": "Batpurev", "last_name": "Battulga", "name": null }, { "creator_type": "author", "first_name": "Nobuhiko", "last_name": "Ohno", "name": null }, { "creator_type": "author", "first_name": "Toru", "last_name": "Hara", "name": null }, { "creator_type": "author", "first_name": "Rina", "last_name": "Kunishige", "name": null }, { "creator_type": "author", "first_name": "Mamiko", "last_name": "Masutani", "name": null }, { "creator_type": "author", "first_name": "Keita", "last_name": "Negishi", "name": null }, { "creator_type": "author", "first_name": "Kazuomi", "last_name": "Kario", "name": null }, { "creator_type": "author", "first_name": "Kazuhiko", "last_name": "Kotani", "name": null }, { "creator_type": "author", "first_name": "Toshiyuki", "last_name": "Yamada", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Nagata", "name": null }, { "creator_type": "author", "first_name": "Issei", "last_name": "Komuro", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Itoh", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Kurosu", "name": null }, { "creator_type": "author", "first_name": "Masayuki", "last_name": "Murata", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Kuro-O", "name": null } ], "identifiers": { "doi": { "normalized": "10.1172/jci145693" }, "pmcid": { "normalized": "PMC8363285" }, "pmid": { "normalized": "34185705" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Body Fluids", "descriptor_ui": "D001826", "major_topic": false }, { "descriptor": "Calcium Phosphates", "descriptor_ui": "D002130", "major_topic": false }, { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "Crystallization", "descriptor_ui": "D003460", "major_topic": false }, { "descriptor": "Diet, Western", "descriptor_ui": "D066273", "major_topic": false }, { "descriptor": "Disease Progression", "descriptor_ui": "D018450", "major_topic": false }, { "descriptor": "Endocytosis", "descriptor_ui": "D004705", "major_topic": false }, { "descriptor": "Fibroblast Growth Factor-23", "descriptor_ui": "D000089703", "major_topic": false }, { "descriptor": "Fibroblast Growth Factors", "descriptor_ui": "D005346", "major_topic": false }, { "descriptor": "Homeostasis", "descriptor_ui": "D006706", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Kidney Tubules", "descriptor_ui": "D007684", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Phosphates", "descriptor_ui": "D010710", "major_topic": false }, { "descriptor": "Renal Insufficiency, Chronic", "descriptor_ui": "D051436", "major_topic": false }, { "descriptor": "Toll-Like Receptor 4", "descriptor_ui": "D051197", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Aug 16", "date_precision": "day", "issue": "16", "normalized_date": "2021-08-16", "pages": "145693", "proceedings_title": null, "publisher": "", "title": "The Journal of clinical investigation", "volume": "131", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Calcium phosphate microcrystals in the renal tubular fluid accelerate chronic kidney disease progression.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Hepatocellular carcinoma (HCC) is the third leading cause of cancer death worldwide. Additionally, the efficacy of targeted molecular therapies with multiple tyrosine kinase inhibitors is limited. In this study, we focused on the cellular signaling pathways common to diverse HCC cells and used quantitative reverse phase protein array (RPPA) and statistical analyses to elucidate the molecular mechanisms determining its malignancy. We examined the heterogeneity of 17 liver cancer cell lines by performing cluster analysis of their expression of CD90 and EpCAM cancer stem cell markers. Gaussian mixture model clustering identified three dominant clusters: CD90-positive and EpCAM-negative (CD90+), EpCAM-positive and CD90-negative (EpCAM+) and EpCAM-negative and CD90-negative (Neutral). A multivariate analysis by partial least squares revealed that the former two cell populations showed distinct patterns of protein expression and phosphorylation in the EGFR and EphA2 signaling pathways. The CD90+ cells exhibited higher abundance of AKT, EphA2 and its phosphorylated form at Ser(897), whereas the EpCAM+ cells exhibited higher abundance of ERK, RSK and its phosphorylated form. This demonstrates that pro-oncogenic, ligand-independent EphA2 signaling plays a dominant role in CD90+ cells with higher motility and metastatic activity than EpCAM+ cells. We also showed that an AKT inhibitor reduced the proliferation and survival of CD90+ cells but did not affect those of EpCAM+ cells. Taken together, our results suggest that AKT activation may be a key pro-oncogenic regulator in HCC.", "classifications": [ { "id": "Suzuki", "label": "Group Suzuki", "parent": "Takekawa", "type": "group" }, { "id": "Takekawa", "label": "Team Takekawa", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Nobuhiko", "last_name": "Asakura", "name": null }, { "creator_type": "author", "first_name": "Naotoshi", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Muroi", "name": null }, { "creator_type": "author", "first_name": "Yosui", "last_name": "Nojima", "name": null }, { "creator_type": "author", "first_name": "Taro", "last_name": "Yamashita", "name": null }, { "creator_type": "author", "first_name": "Shuichi", "last_name": "Kaneko", "name": null }, { "creator_type": "author", "first_name": "Kazuki", "last_name": "Ikeda", "name": null }, { "creator_type": "author", "first_name": "Naohiko", "last_name": "Koshikawa", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Suzuki", "name": null } ], "identifiers": { "doi": { "normalized": "10.3390/ijms22168652" }, "pmcid": { "normalized": "PMC8395527" }, "pmid": { "normalized": "34445353" } }, "mesh": [ { "descriptor": "Biomarkers, Tumor", "descriptor_ui": "D014408", "major_topic": false }, { "descriptor": "Carcinogenesis", "descriptor_ui": "D063646", "major_topic": false }, { "descriptor": "Carcinoma, Hepatocellular", "descriptor_ui": "D006528", "major_topic": false }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Epithelial Cell Adhesion Molecule", "descriptor_ui": "D000071858", "major_topic": false }, { "descriptor": "Hep G2 Cells", "descriptor_ui": "D056945", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Liver Neoplasms", "descriptor_ui": "D008113", "major_topic": false }, { "descriptor": "Neoplastic Stem Cells", "descriptor_ui": "D014411", "major_topic": false }, { "descriptor": "Receptor, EphA2", "descriptor_ui": "D036104", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Thy-1 Antigens", "descriptor_ui": "D018800", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Aug 11", "date_precision": "day", "issue": "16", "normalized_date": "2021-08-11", "pages": "8652", "proceedings_title": null, "publisher": "", "title": "International journal of molecular sciences", "volume": "22", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Expression of Cancer Stem Cell Markers EpCAM and CD90 Is Correlated with Anti- and Pro-Oncogenic EphA2 Signaling in Hepatocellular Carcinoma.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "A long-standing question in porphyrin chemistry is why pyrrole monomers selectively form tetrapyrrolic macrocycles, whereas the corresponding tripyrrolic macrocycles are never observed. Calix[3]pyrrole, a tripyrrolic porphyrinogen-like macrocycle bearing three sp(3)-carbon linkages, is a missing link molecule that might hold the key to this enigma; however, it has remained elusive. Here we report the synthesis and strain-induced transformations of calix[3]pyrrole and its furan analogue, calix[3]furan. These macrocycles are readily accessed from cyclic oligoketones. Crystallographic and theoretical analyses reveal that these three-subunit systems possess the largest strain energy among known calix[n]-type macrocycles. The ring-strain triggers transformation of calix[3]pyrrole into first calix[6]pyrrole and then calix[4]pyrrole under porphyrin cyclization conditions. The present results help explain the absence of naturally occurring three-pyrrole macrocycles and the fact that they are not observed as products or intermediate during classic porphyrin syntheses.", "classifications": [ { "id": "Hijikata", "label": "Group Hijikata", "parent": "Tsuchiya", "type": "group" }, { "id": "Tsuchiya", "label": "Team Tsuchiya", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yuya", "last_name": "Inaba", "name": null }, { "creator_type": "author", "first_name": "Yu", "last_name": "Nomata", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Ide", "name": null }, { "creator_type": "author", "first_name": "Jenny", "last_name": "Pirillo", "name": null }, { "creator_type": "author", "first_name": "Yuh", "last_name": "Hijikata", "name": null }, { "creator_type": "author", "first_name": "Tomoki", "last_name": "Yoneda", "name": null }, { "creator_type": "author", "first_name": "Atsuhiro", "last_name": "Osuka", "name": null }, { "creator_type": "author", "first_name": "Jonathan L.", "last_name": "Sessler", "name": null }, { "creator_type": "author", "first_name": "Yasuhide", "last_name": "Inokuma", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/jacs.1c06331" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "34320322" } }, "mesh": [], "publication": { "conference_name": null, "date": "2021 Aug 11", "date_precision": "day", "issue": "31", "normalized_date": "2021-08-11", "pages": "12355-12360", "proceedings_title": null, "publisher": "", "title": "Journal of the American Chemical Society", "volume": "143", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Calix[3]pyrrole: A Missing Link in Porphyrin-Related Chemistry.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "A series of chiral Au(13) nanoclusters were synthesized via the direct reduction of achiral dinuclear Au(i) halide complexes ligated by ortho-xylyl-linked bis-N-heterocyclic carbene (NHC) ligands. A broad range of functional groups are tolerated as wingtip substituents, allowing for the synthesis of a variety of functionalized chiral Au(13) nanoclusters. Single crystal X-ray crystallography confirmed the molecular formula to be [Au(13)(bisNHC)(5)Cl(2)]Cl(3), with a chiral helical arrangement of the five bidentate NHC ligands around the icosahedral Au(13) core. This Au(13) nanocluster is highly luminescent, with a quantum yield of 23%. The two enantiomers of the Au(13) clusters can be separated by chiral HPLC, and the isolated enantiomers were characterized by circular dichroism spectroscopy. The clusters show remarkable stability, including configurational stability, opening the door to further investigation of the effect of chirality on these clusters.", "classifications": [ { "id": "Nanbo", "label": "Group Nanbo", "parent": "Tsuchiya", "type": "group" }, { "id": "Tsuchiya", "label": "Team Tsuchiya", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Hong", "last_name": "Yi", "name": null }, { "creator_type": "author", "first_name": "Kimberly M.", "last_name": "Osten", "name": null }, { "creator_type": "author", "first_name": "Tetyana I.", "last_name": "Levchenko", "name": null }, { "creator_type": "author", "first_name": "Alex J.", "last_name": "Veinot", "name": null }, { "creator_type": "author", "first_name": "Yoshitaka", "last_name": "Aramaki", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Ooi", "name": null }, { "creator_type": "author", "first_name": "Masakazu", "last_name": "Nambo", "name": null }, { "creator_type": "author", "first_name": "Cathleen M.", "last_name": "Crudden", "name": null } ], "identifiers": { "doi": { "normalized": "10.1039/d1sc03076k" }, "pmcid": { "normalized": "PMC8356741" }, "pmid": { "normalized": "34447535" } }, "mesh": [], "publication": { "conference_name": null, "date": "2021 Aug 11", "date_precision": "day", "issue": "31", "normalized_date": "2021-08-11", "pages": "10436-10440", "proceedings_title": null, "publisher": "", "title": "Chemical science", "volume": "12", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Synthesis and enantioseparation of chiral Au(13) nanoclusters protected by bis-N-heterocyclic carbene ligands.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "A double-stranded spiroborate helicate bearing a bisporphyrin unit in the middle forms an inclusion complex with electron-deficient aromatic guests that are sandwiched between the porphyrins. In the present study, we systematically investigated the effects of size, electron density, and substituents of a series of aromatic guests on inclusion complex formations within the bisporphyrin. The thermodynamic and kinetic behaviors during the guest-encapsulation process were also investigated in detail. The guest-encapsulation abilities in the helicate increased with the increasing core sizes of the electron-deficient aromatic guests and decreased with the increasing bulkiness and number of substituents of the guests. Among the naphthalenediimide derivatives, those with bulky N-substituents at both ends hardly formed an inclusion complex. Instead, they formed a [2]rotaxane-like inclusion complex through the water-mediated dynamic B-O bond cleavage/reformation of the spiroborate groups of the helicate, which enhanced the conformational flexibility of the helicate to enlarge the bisporphyrin cavity and form an inclusion complex. Based on the X-ray crystal structure of a unique pacman-like 1:1 inclusion complex between the helicate and an ammonium cation as well as the molecular dynamics simulation results, a plausible mechanism for the inclusion of a planar aromatic guest within the helicate is also proposed.", "classifications": [ { "id": "Hijikata", "label": "Group Hijikata", "parent": "Tsuchiya", "type": "group" }, { "id": "Tsuchiya", "label": "Team Tsuchiya", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Naoki", "last_name": "Ousaka", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Hiroki", "last_name": "Iida", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Iwata", "name": null }, { "creator_type": "author", "first_name": "Shingo", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Rafael", "last_name": "Souza", "name": null }, { "creator_type": "author", "first_name": "Yuh", "last_name": "Hijikata", "name": null }, { "creator_type": "author", "first_name": "Stephan", "last_name": "Irle", "name": null }, { "creator_type": "author", "first_name": "Eiji", "last_name": "Yashima", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/acs.joc.1c01155" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "34282918" } }, "mesh": [ { "descriptor": "Correctional Facilities", "descriptor_ui": "D000081682", "major_topic": false }, { "descriptor": "Electrons", "descriptor_ui": "D004583", "major_topic": true }, { "descriptor": "Kinetics", "descriptor_ui": "D007700", "major_topic": false }, { "descriptor": "Molecular Dynamics Simulation", "descriptor_ui": "D056004", "major_topic": true }, { "descriptor": "Thermodynamics", "descriptor_ui": "D013816", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Aug 6", "date_precision": "day", "issue": "15", "normalized_date": "2021-08-06", "pages": "10501-10516", "proceedings_title": null, "publisher": "", "title": "The Journal of organic chemistry", "volume": "86", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Encapsulation of Aromatic Guests in the Bisporphyrin Cavity of a Double-Stranded Spiroborate Helicate: Thermodynamic and Kinetic Studies and the Encapsulation Mechanism.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "During the development of analgesic tolerance to morphine, the V1b vasopressin receptor has been proposed to bind to beta-arrestin 2 and the micro-opioid receptor to enable their interaction. However, direct evidence of such a high-order complex is lacking. Using bioluminescent resonance energy transfer between a split Nanoluciferase and the Venus fluorescent protein, the NanoBit-NanoBRET system, we found that beta-arrestin 2 closely located near the heteromer micro-V1b receptor in the absence of an agonist and moved closer to the receptor carboxyl-termini upon agonist stimulation. An additive effect of the two agonists for opioid and vasopressin receptors was detected on the NanoBRET between the micro-V1b heteromer and beta-arrestin 2. To increase the agonist response of NanoBRET, the ratio of the donor luminophore to the acceptor fluorophore was decreased to the detection limit of luminescence. In the first phase of access, beta-arrestin 2 was likely to bind to the unstimulated V1b receptor in both its phosphorylated and unphosphorylated forms. In contrast, the second-phase access of beta-arrestin 2 was agonist dependent, indicating a possible pharmacological intervention strategy. Therefore, our efficient method should be useful for evaluating chemicals that directly target the vasopressin binding site in the micro-V1b heteromer to reduce the second-phase access of beta-arrestin 2 and thereby to alleviate tolerance to morphine analgesia.", "classifications": [ { "id": "Kuchimaru", "label": "Group Kuchimaru", "parent": "Shintaku", "type": "group" }, { "id": "Shintaku", "label": "Team Shintaku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Nuttawadee", "last_name": "Ngamlertwong", "name": null }, { "creator_type": "author", "first_name": "Hiroyoshi", "last_name": "Tsuchiya", "name": null }, { "creator_type": "author", "first_name": "Yuta", "last_name": "Mochimaru", "name": null }, { "creator_type": "author", "first_name": "Morio", "last_name": "Azuma", "name": null }, { "creator_type": "author", "first_name": "Takahiro", "last_name": "Kuchimaru", "name": null }, { "creator_type": "author", "first_name": "Taka-Aki", "last_name": "Koshimizu", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41598-021-94894-y" }, "pmcid": { "normalized": "PMC8339129" }, "pmid": { "normalized": "34349143" } }, "mesh": [ { "descriptor": "Analgesics, Opioid", "descriptor_ui": "D000701", "major_topic": false }, { "descriptor": "beta-Arrestin 2", "descriptor_ui": "D000071560", "major_topic": false }, { "descriptor": "Binding Sites", "descriptor_ui": "D001665", "major_topic": false }, { "descriptor": "Drug Tolerance", "descriptor_ui": "D004361", "major_topic": false }, { "descriptor": "HEK293 Cells", "descriptor_ui": "D057809", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Morphine", "descriptor_ui": "D009020", "major_topic": false }, { "descriptor": "Phosphorylation", "descriptor_ui": "D010766", "major_topic": false }, { "descriptor": "Receptors, Vasopressin", "descriptor_ui": "D017483", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Aug 4", "date_precision": "day", "issue": "1", "normalized_date": "2021-08-04", "pages": "15813", "proceedings_title": null, "publisher": "", "title": "Scientific reports", "volume": "11", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Agonist dependency of the second phase access of beta-arrestin 2 to the heteromeric micro-V1b receptor.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The trapping of paraffins is beneficial compared to selective olefin adsorption for adsorptive olefin purification from a process engineering point of view. Here we demonstrate the use of a series of Zn2(X-bdc)2(dabco) (where X-bdc2- is bdc2- = 1,4-benzenedicarboxylate with substituting groups X, DM-bdc2- = 2,5-dimethyl-1,4-benzenedicarboxylate or TM-bdc2- = 2,3,5,6-tetramethyl-1,4-benzenedicarboxylate and dabco = diazabicyclo[2.2.2.]octane) metal-organic frameworks (MOFs) for the adsorptive removal of ethane from ethylene streams. The best performing material from this series is Zn2(TM-bdc)2(dabco) (DMOF-TM), which shows a high ethane uptake of 5.31 mmol g-1 at 110 kPa, with a good IAST selectivity of 1.88 towards ethane over ethylene. Through breakthrough measurements a high productivity of 13.1 L kg-1 per breakthrough is revealed with good reproducibility over five consecutive cycles. Molecular simulations show that the methyl groups of DMOF-TM are forming a van der Waals trap with the methylene groups from dabco, snuggly fitting the ethane. Further, rarely used high pressure coadsorption measurements, in pressure regimes that most scientific studies on hydrocarbon separation on MOFs ignore, reveal an increase in ethane capacity and selectivity for binary mixtures with increased pressures. The coadsorption measurements reveal good selectivity of 1.96 at 1000 kPa, which is verified also through IAST calculations up to 3000 kPa. This study overall showcases the opportunities that pore engineering by alkyl group incorporation and pressure increase offer to improve hydrocarbon separation in reticular materials.", "classifications": [ { "id": "Hijikata", "label": "Group Hijikata", "parent": "Tsuchiya", "type": "group" }, { "id": "Tsuchiya", "label": "Team Tsuchiya", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Andreas", "last_name": "Schneemann", "name": null }, { "creator_type": "author", "first_name": "Yuan", "last_name": "Jing", "name": null }, { "creator_type": "author", "first_name": "Jack D.", "last_name": "Evans", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Toyao", "name": null }, { "creator_type": "author", "first_name": "Yuh", "last_name": "Hijikata", "name": null }, { "creator_type": "author", "first_name": "Yuichi", "last_name": "Kamiya", "name": null }, { "creator_type": "author", "first_name": "Ken-Ichi", "last_name": "Shimizu", "name": null }, { "creator_type": "author", "first_name": "Nicholas C.", "last_name": "Burtch", "name": null }, { "creator_type": "author", "first_name": "Shin-Ichiro", "last_name": "Noro", "name": null } ], "identifiers": { "doi": { "normalized": "10.1039/d1dt01477c" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "34240094" } }, "mesh": [], "publication": { "conference_name": null, "date": "2021 Aug 4", "date_precision": "day", "issue": "30", "normalized_date": "2021-08-04", "pages": "10423-10435", "proceedings_title": null, "publisher": "", "title": "Dalton transactions (Cambridge, England : 2003)", "volume": "50", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Alkyl decorated metal-organic frameworks for selective trapping of ethane from ethylene above ambient pressures.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Although Raman spectroscopy has been used for the quantitative analysis of samples in many fields, including material science, biomedical, and pharmaceutical research, its low sensitivity hindered the application of the analytical capability for high-throughput screening. Here, we developed a high-throughput Raman screening system that can analyze hundreds of specimens in a multiwell plate simultaneously. Multiple high numerical aperture (NA) lenses are assembled under each well in the multiwell plate to detect Raman scattering simultaneously with high sensitivity. The Raman spectrum of 192 samples loaded on a standard 384-well plate can be analyzed simultaneously. With the developed system, the throughput of Raman measurement was significantly improved (about 100 times) compared to conventional Raman instruments based on a single-point measurement. By using the developed system, we demonstrated high-throughput Raman screening to investigate drug polymorphism and identify a small-molecule binding site in a protein. Furthermore, the same system was used to demonstrate high-speed chemical mapping of a centimeter-sized pork slice.", "classifications": [ { "id": "Fujita", "label": "Group Fujita", "parent": "Fujita", "type": "group" }, { "id": "Sodeoka", "label": "Group Sodeoka", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Kawagoe", "name": null }, { "creator_type": "author", "first_name": "Jun", "last_name": "Ando", "name": null }, { "creator_type": "author", "first_name": "Miwako", "last_name": "Asanuma", "name": null }, { "creator_type": "author", "first_name": "Kosuke", "last_name": "Dodo", "name": null }, { "creator_type": "author", "first_name": "Tetsuya", "last_name": "Miyano", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Ueda", "name": null }, { "creator_type": "author", "first_name": "Mikiko", "last_name": "Sodeoka", "name": null }, { "creator_type": "author", "first_name": "Katsumasa", "last_name": "Fujita", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41598-021-95139-8" }, "pmcid": { "normalized": "PMC8333358" }, "pmid": { "normalized": "34344945" } }, "mesh": [], "publication": { "conference_name": null, "date": "2021 Aug 3", "date_precision": "day", "issue": "1", "normalized_date": "2021-08-03", "pages": "15742", "proceedings_title": null, "publisher": "", "title": "Scientific reports", "volume": "11", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Multiwell Raman plate reader for high-throughput biochemical screening.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Prostaglandin E2 (PGE2) promotes tumor progression through evasion of antitumor immunity. In stark contrast to cyclooxygenase-dependent production of PGE2, little is known whether PGE2 secretion is regulated within tumor tissues. Here, we show that VEGF-dependent release of thromboxane A2 (TXA2) triggers Ca(2+) transients in tumor cells, culminating in PGE2 secretion and subsequent immune evasion in the early stages of tumorigenesis. Ca(2+) transients caused cPLA2 activation and triggered the arachidonic acid cascade. Ca(2+) transients were monitored as the surrogate marker of PGE2 secretion. Intravital imaging of Braf(V600E) mouse melanoma cells revealed that the proportion of cells exhibiting Ca(2+) transients is markedly higher in vivo than in vitro. The TXA2 receptor was indispensable for the Ca(2+) transients in vivo, high intratumoral PGE2 concentration, and evasion of antitumor immunity. Notably, treatment with a VEGF receptor antagonist and an anti-VEGF antibody rapidly suppressed Ca(2+) transients and reduced TXA2 and PGE2 concentrations in tumor tissues. These results identify the VEGF-TXA2 axis as a critical promoter of PGE2-dependent tumor immune evasion, providing a molecular basis underlying the immunomodulatory effect of anti-VEGF therapies. SIGNIFICANCE: This study identifies the VEGF-TXA2 axis as a potentially targetable regulator of PGE2 secretion, which provides novel strategies for prevention and treatment of multiple types of malignancies.", "classifications": [], "creators": [ { "creator_type": "author", "first_name": "Yoshinobu", "last_name": "Konishi", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Ichise", "name": null }, { "creator_type": "author", "first_name": "Tetsuya", "last_name": "Watabe", "name": null }, { "creator_type": "author", "first_name": "Choji", "last_name": "Oki", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Tsukiji", "name": null }, { "creator_type": "author", "first_name": "Yoko", "last_name": "Hamazaki", "name": null }, { "creator_type": "author", "first_name": "Yasuhiro", "last_name": "Murakawa", "name": null }, { "creator_type": "author", "first_name": "Akifumi", "last_name": "Takaori-Kondo", "name": null }, { "creator_type": "author", "first_name": "Kenta", "last_name": "Terai", "name": null }, { "creator_type": "author", "first_name": "Michiyuki", "last_name": "Matsuda", "name": null } ], "identifiers": { "doi": { "normalized": "10.1158/0008-5472.can-20-4245" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "34035084" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Dinoprostone", "descriptor_ui": "D015232", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Immune Evasion", "descriptor_ui": "D057131", "major_topic": false }, { "descriptor": "Intravital Microscopy", "descriptor_ui": "D000069416", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Nude", "descriptor_ui": "D008819", "major_topic": false }, { "descriptor": "Vascular Endothelial Growth Factor A", "descriptor_ui": "D042461", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Aug 1", "date_precision": "day", "issue": "15", "normalized_date": "2021-08-01", "pages": "4124-4132", "proceedings_title": null, "publisher": "", "title": "Cancer research", "volume": "81", "year": 2021 }, "ssbd": { "database": [ "ssbd-database-000219" ], "repository": [ "ssbd-repos-000219" ] }, "title": "Intravital Imaging Identifies the VEGF-TXA2 Axis as a Critical Promoter of PGE2 Secretion from Tumor Cells and Immune Evasion.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Neuronal birthdate is one of the major determinants of neuronal phenotypes. However, most birthdating methods are retrospective in nature, allowing very little experimental access to the classified neuronal subsets. Here, we introduce four neurogenic tagging mouse lines, which can assign CreER-loxP recombination to neuron subsets that share the same differentiation timing in living animals and enable various experimental manipulations of the classified subsets. We constructed a brain atlas of the neurogenic tagging mouse lines (NeuroGT), which includes holistic image data of the loxP-recombined neurons and their processes across the entire brain that were tagged on each single day during the neurodevelopmental period. This image database, which is open to the public, offers investigators the opportunity to find specific neurogenic tagging driver lines and the stages of tagging appropriate for their own research purposes.", "classifications": [ { "id": "Onami", "label": "Group Onami", "parent": "Fujiwara", "type": "group" }, { "id": "Fujiwara", "label": "Team Fujiwara", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Tatsumi", "last_name": "Hirata", "name": null }, { "creator_type": "author", "first_name": "Yukako", "last_name": "Tohsato", "name": null }, { "creator_type": "author", "first_name": "Hiroya", "last_name": "Itoga", "name": null }, { "creator_type": "author", "first_name": "Go", "last_name": "Shioi", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Kiyonari", "name": null }, { "creator_type": "author", "first_name": "Sanae", "last_name": "Oka", "name": null }, { "creator_type": "author", "first_name": "Toshihiko", "last_name": "Fujimori", "name": null }, { "creator_type": "author", "first_name": "Shuichi", "last_name": "Onami", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.crmeth.2021.100012" }, "pmcid": { "normalized": "PMC9017123" }, "pmid": { "normalized": "35474959" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Brain", "descriptor_ui": "D001921", "major_topic": true }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": true }, { "descriptor": "Retrospective Studies", "descriptor_ui": "D012189", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Jul 26", "date_precision": "day", "issue": "3", "normalized_date": "2021-07-26", "pages": "100012", "proceedings_title": null, "publisher": "", "title": "Cell reports methods", "volume": "1", "year": 2021 }, "ssbd": { "database": [ "ssbd-database-000140" ], "repository": [ "ssbd-repos-000140" ] }, "title": "NeuroGT: A brain atlas of neurogenic tagging CreER drivers for birthdate-based classification and manipulation of mouse neurons.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "At the early stage of cancer development, oncogenic mutations often cause multilayered epithelial structures. However, the underlying molecular mechanism still remains enigmatic. By performing a series of screenings targeting plasma membrane proteins, we have found that collagen XVII (COL17A1) and CD44 accumulate in RasV12-, Src-, or ErbB2-transformed epithelial cells. In addition, the expression of COL17A1 and CD44 is also regulated by cell density and upon apical cell extrusion. We further demonstrate that the expression of COL17A1 and CD44 is profoundly upregulated at the upper layers of multilayered, transformed epithelia in vitro and in vivo. The accumulated COL17A1 and CD44 suppress mitochondrial membrane potential and reactive oxygen species (ROS) production. The diminished intracellular ROS level then promotes resistance against ferroptosis-mediated cell death upon cell extrusion, thereby positively regulating the formation of multilayered structures. To further understand the functional role of COL17A1, we performed comprehensive metabolome analysis and compared intracellular metabolites between RasV12 and COL17A1-knockout RasV12 cells. The data imply that COL17A1 regulates the metabolic pathway from the GABA shunt to mitochondrial complex I through succinate, thereby suppressing the ROS production. Moreover, we demonstrate that CD44 regulates membrane accumulation of COL17A1 in multilayered structures. These results suggest that CD44 and COL17A1 are crucial regulators for the clonal expansion of transformed cells within multilayered epithelia, thus being potential targets for early diagnosis and preventive treatment for precancerous lesions.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Kei", "last_name": "Kozawa", "name": null }, { "creator_type": "author", "first_name": "Miho", "last_name": "Sekai", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Ohba", "name": null }, { "creator_type": "author", "first_name": "Shoko", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Hiroaki", "last_name": "Sako", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Maruyama", "name": null }, { "creator_type": "author", "first_name": "Mai", "last_name": "Kakeno", "name": null }, { "creator_type": "author", "first_name": "Takanobu", "last_name": "Shirai", "name": null }, { "creator_type": "author", "first_name": "Keisuke", "last_name": "Kuromiya", "name": null }, { "creator_type": "author", "first_name": "Tomoko", "last_name": "Kamasaki", "name": null }, { "creator_type": "author", "first_name": "Koki", "last_name": "Kohashi", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Susumu", "last_name": "Ishikawa", "name": null }, { "creator_type": "author", "first_name": "Nanami", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Shota", "last_name": "Asano", "name": null }, { "creator_type": "author", "first_name": "Hironori", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Nobuyuki", "last_name": "Tanimura", "name": null }, { "creator_type": "author", "first_name": "Yohei", "last_name": "Mukai", "name": null }, { "creator_type": "author", "first_name": "Noriko", "last_name": "Gotoh", "name": null }, { "creator_type": "author", "first_name": "Mishie", "last_name": "Tanino", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Ken", "last_name": "Natsuga", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Tomonori", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Yukihiro", "last_name": "Yabuta", "name": null }, { "creator_type": "author", "first_name": "Mitinori", "last_name": "Saitou", "name": null }, { "creator_type": "author", "first_name": "Takahiro", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Kenkyo", "last_name": "Matsuura", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Tsunoda", "name": null }, { "creator_type": "author", "first_name": "Toyone", "last_name": "Kikumori", "name": null }, { "creator_type": "author", "first_name": "Tadashi", "last_name": "Iida", "name": null }, { "creator_type": "author", "first_name": "Yasuyuki", "last_name": "Mizutani", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Miyai", "name": null }, { "creator_type": "author", "first_name": "Kozo", "last_name": "Kaibuchi", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Enomoto", "name": null }, { "creator_type": "author", "first_name": "Yasuyuki", "last_name": "Fujita", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.cub.2021.04.078" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "34087104" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "Cell Transformation, Neoplastic", "descriptor_ui": "D002471", "major_topic": true }, { "descriptor": "Dogs", "descriptor_ui": "D004285", "major_topic": false }, { "descriptor": "Epithelium", "descriptor_ui": "D004848", "major_topic": false }, { "descriptor": "Ferroptosis", "descriptor_ui": "D000079403", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Hyaluronan Receptors", "descriptor_ui": "D018960", "major_topic": false }, { "descriptor": "Madin Darby Canine Kidney Cells", "descriptor_ui": "D061985", "major_topic": false }, { "descriptor": "Membrane Potential, Mitochondrial", "descriptor_ui": "D053078", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Non-Fibrillar Collagens", "descriptor_ui": "D024041", "major_topic": false }, { "descriptor": "Reactive Oxygen Species", "descriptor_ui": "D017382", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Jul 26", "date_precision": "day", "issue": "14", "normalized_date": "2021-07-26", "pages": "3086-3097.e7", "proceedings_title": null, "publisher": "", "title": "Current biology : CB", "volume": "31", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "The CD44/COL17A1 pathway promotes the formation of multilayered, transformed epithelia.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Haploinsufficiency of EHMT1, which encodes histone H3 lysine 9 (H3K9) methyltransferase G9a-like protein (GLP), causes Kleefstra syndrome (KS), a complex disorder of developmental delay and intellectual disability. Here, we examined whether postnatal supply of GLP can reverse the neurological phenotypes seen in Ehmt1 (Delta/+) mice as a KS model. Ubiquitous GLP supply from the juvenile stage ameliorated behavioral abnormalities in Ehmt1 (Delta/+) mice. Postnatal neuron-specific GLP supply was not sufficient for the improvement of abnormal behaviors but still reversed the reduction of H3K9me2 and spine number in Ehmt1 (Delta/+) mice. Interestingly, some inflammatory genes, including IL-1beta (Il1b), were upregulated and activated microglial cells increased in the Ehmt1 (Delta/+) brain, and such phenotypes were also reversed by neuron-specific postnatal GLP supply. Il1b inactivation canceled the microglial and spine number phenotypes in the Ehmt1 (Delta/+) mice. Thus, H3K9me2 and some neurological phenotypes are reversible, but behavioral abnormalities are more difficult to improve depending on the timing of GLP supply.", "classifications": [ { "id": "Nikaido", "label": "Group Nikaido", "parent": "Fujiwara", "type": "group" }, { "id": "Fujiwara", "label": "Team Fujiwara", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Ayumi", "last_name": "Yamada", "name": null }, { "creator_type": "author", "first_name": "Takae", "last_name": "Hirasawa", "name": null }, { "creator_type": "author", "first_name": "Kayako", "last_name": "Nishimura", "name": null }, { "creator_type": "author", "first_name": "Chikako", "last_name": "Shimura", "name": null }, { "creator_type": "author", "first_name": "Naomi", "last_name": "Kogo", "name": null }, { "creator_type": "author", "first_name": "Kei", "last_name": "Fukuda", "name": null }, { "creator_type": "author", "first_name": "Madoka", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Masaki", "last_name": "Yokomori", "name": null }, { "creator_type": "author", "first_name": "Tetsutaro", "last_name": "Hayashi", "name": null }, { "creator_type": "author", "first_name": "Mana", "last_name": "Umeda", "name": null }, { "creator_type": "author", "first_name": "Mika", "last_name": "Yoshimura", "name": null }, { "creator_type": "author", "first_name": "Yoichiro", "last_name": "Iwakura", "name": null }, { "creator_type": "author", "first_name": "Itoshi", "last_name": "Nikaido", "name": null }, { "creator_type": "author", "first_name": "Shigeyoshi", "last_name": "Itohara", "name": null }, { "creator_type": "author", "first_name": "Yoichi", "last_name": "Shinkai", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.isci.2021.102741" }, "pmcid": { "normalized": "PMC8258976" }, "pmid": { "normalized": "34258564" } }, "mesh": [], "publication": { "conference_name": null, "date": "2021 Jul 23", "date_precision": "day", "issue": "7", "normalized_date": "2021-07-23", "pages": "102741", "proceedings_title": null, "publisher": "", "title": "iScience", "volume": "24", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Derepression of inflammation-related genes link to microglia activation and neural maturation defect in a mouse model of Kleefstra syndrome.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Radiogenomics use non-invasively obtained imaging data, such as magnetic resonance imaging (MRI), to predict critical biomarkers of patients. Developing an accurate machine learning (ML) technique for MRI requires data from hundreds of patients, which cannot be gathered from any single local hospital. Hence, a model universally applicable to multiple cohorts/hospitals is required. We applied various ML and image pre-processing procedures on a glioma dataset from The Cancer Image Archive (TCIA, n = 159). The models that showed a high level of accuracy in predicting glioblastoma or WHO Grade II and III glioma using the TCIA dataset, were then tested for the data from the National Cancer Center Hospital, Japan (NCC, n = 166) whether they could maintain similar levels of high accuracy. Results: we confirmed that our ML procedure achieved a level of accuracy (AUROC = 0.904) comparable to that shown previously by the deep-learning methods using TCIA. However, when we directly applied the model to the NCC dataset, its AUROC dropped to 0.383. Introduction of standardization and dimension reduction procedures before classification without re-training improved the prediction accuracy obtained using NCC (0.804) without a loss in prediction accuracy for the TCIA dataset. Furthermore, we confirmed the same tendency in a model for IDH1/2 mutation prediction with standardization and application of dimension reduction that was also applicable to multiple hospitals. Our results demonstrated that overfitting may occur when an ML method providing the highest accuracy in a small training dataset is used for different heterogeneous data sets, and suggested a promising process for developing an ML method applicable to multiple cohorts.", "classifications": [ { "id": "Hamamoto", "label": "Group Hamamoto", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Risa K.", "last_name": "Kawaguchi", "name": null }, { "creator_type": "author", "first_name": "Masamichi", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Mototaka", "last_name": "Miyake", "name": null }, { "creator_type": "author", "first_name": "Manabu", "last_name": "Kinoshita", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Koichi", "last_name": "Ichimura", "name": null }, { "creator_type": "author", "first_name": "Ryuji", "last_name": "Hamamoto", "name": null }, { "creator_type": "author", "first_name": "Yoshitaka", "last_name": "Narita", "name": null }, { "creator_type": "author", "first_name": "Jun", "last_name": "Sese", "name": null } ], "identifiers": { "doi": { "normalized": "10.3390/cancers13143611" }, "pmcid": { "normalized": "PMC8306149" }, "pmid": { "normalized": "34298824" } }, "mesh": [], "publication": { "conference_name": null, "date": "2021 Jul 19", "date_precision": "day", "issue": "14", "normalized_date": "2021-07-19", "pages": "3611", "proceedings_title": null, "publisher": "", "title": "Cancers", "volume": "13", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Assessing Versatile Machine Learning Models for Glioma Radiogenomic Studies across Hospitals.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Osimertinib is a third-generation, irreversible oral EGFR-tyrosine kinase inhibitor), that potently inhibits EGFR-tyrosine kinase inhibitor-sensitizing mutations and T790M resistance mutations together with efficacy in CNS metastases in patients with non-small-cell lung cancer (NSCLC). Here we describe the rationale and design for the Phase III NeoADAURA study (NCT04351555), which will evaluate neoadjuvant osimertinib with or without chemotherapy versus chemotherapy alone prior to surgery, in patients with resectable stage II–IIIB N2 EGFR mutation-positive NSCLC. The primary end point is centrally assessed major pathological response at the time of resection. Secondary end points include event-free survival, pathological complete response, nodal downstaging at the time of surgery, disease-free survival, overall survival and health-related quality of life. Safety and tolerability will also be assessed.Trial Registration number: NCT04351555 (ClinicalTrials.gov)", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Masahiro", "last_name": "Tsuboi", "name": null }, { "creator_type": "author", "first_name": "Walter", "last_name": "Weder", "name": null }, { "creator_type": "author", "first_name": "Carles", "last_name": "Escriu", "name": null }, { "creator_type": "author", "first_name": "Collin", "last_name": "Blakely", "name": null }, { "creator_type": "author", "first_name": "Jianxing", "last_name": "He", "name": null }, { "creator_type": "author", "first_name": "Sanja", "last_name": "Dacic", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null }, { "creator_type": "author", "first_name": "Lingmin", "last_name": "Zeng", "name": null }, { "creator_type": "author", "first_name": "Andrew", "last_name": "Walding", "name": null }, { "creator_type": "author", "first_name": "Jamie E.", "last_name": "Chaft", "name": null } ], "identifiers": { "doi": { "normalized": "10.2217/fon-2021-0549" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "34278827" } }, "mesh": [ { "descriptor": "Acrylamides", "descriptor_ui": "D000178", "major_topic": false }, { "descriptor": "Aniline Compounds", "descriptor_ui": "D000814", "major_topic": false }, { "descriptor": "Carcinoma, Non-Small-Cell Lung", "descriptor_ui": "D002289", "major_topic": false }, { "descriptor": "ErbB Receptors", "descriptor_ui": "D066246", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Indoles", "descriptor_ui": "D007211", "major_topic": false }, { "descriptor": "Lung Neoplasms", "descriptor_ui": "D008175", "major_topic": false }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": true }, { "descriptor": "Neoadjuvant Therapy", "descriptor_ui": "D020360", "major_topic": false }, { "descriptor": "Pyrimidines", "descriptor_ui": "D011743", "major_topic": false }, { "descriptor": "Quality of Life", "descriptor_ui": "D011788", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021-07-19", "date_precision": "day", "issue": "31", "normalized_date": "2021-07-19", "pages": "4045-4055", "proceedings_title": null, "publisher": "", "title": "Future Oncology", "volume": "17", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Neoadjuvant osimertinib with/without chemotherapy versus chemotherapy alone for EGFR-mutated resectable non-small-cell lung cancer: NeoADAURA.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "PURPOSE: We assessed the intratumor pharmacokinetics of [fam-] trastuzumab deruxtecan, T-DXd (known as DS-8201a), a novel HER2-targeted antibody-drug conjugate, using phosphor-integrated dots (PID)-imaging analysis to elucidate its pharmacologic mechanism. EXPERIMENTAL DESIGN: We used two mouse xenograft models administered T-DXd at the concentration of 4 mg/kg: (i) a heterogeneous model in which HER2-positive and HER2-negative cell lines were mixed, and (ii) a homogeneous model in which both cell types were transplanted separately into the same mouse. PID imaging involved immunostaining using novel high-intensity fluorescent nanoparticles. The distribution of T-DXd was assessed by PID imaging targeting the parent antibody, trastuzumab, and the payload, DXd, in serial frozen sections, respectively. RESULTS: After T-DXd administration in the heterogeneous model, HER2 expression tended to decrease in a time-dependent manner. The distribution of trastuzumab and DXd was observed by PID imaging along the HER2-positive area throughout the observation period. A detailed comparison of the PID distribution between trastuzumab and DXd showed that trastuzumab matched almost perfectly with the HER2-positive area. In contrast, DXd exhibited widespread distribution in the surrounding HER2-negative area as well. In the HER2-negative tumor of the homogeneous model, the PID distribution of trastuzumab and DXd remained extremely low throughout the observation period. CONCLUSIONS: Our results suggest that T-DXd is distributed to tumor tissues via trastuzumab in a HER2-dependent manner and then to adjacent HER2-negative areas. We successfully visualized the intratumor distribution of T-DXd and its mechanism of action, the so-called \"bystander effect.\"", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Mikiko", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Shigehiro", "last_name": "Yagishita", "name": null }, { "creator_type": "author", "first_name": "Kiyoshi", "last_name": "Sugihara", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Ogitani", "name": null }, { "creator_type": "author", "first_name": "Tadaaki", "last_name": "Nishikawa", "name": null }, { "creator_type": "author", "first_name": "Mayu", "last_name": "Ohuchi", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Teishikata", "name": null }, { "creator_type": "author", "first_name": "Takahiro", "last_name": "Jikoh", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null }, { "creator_type": "author", "first_name": "Kan", "last_name": "Yonemori", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Tamura", "name": null }, { "creator_type": "author", "first_name": "Kosei", "last_name": "Hasegawa", "name": null }, { "creator_type": "author", "first_name": "Akinobu", "last_name": "Hamada", "name": null } ], "identifiers": { "doi": { "normalized": "10.1158/1078-0432.ccr-21-0397" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "33980613" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Camptothecin", "descriptor_ui": "D002166", "major_topic": false }, { "descriptor": "Disease Models, Animal", "descriptor_ui": "D004195", "major_topic": false }, { "descriptor": "Erb-b2 Receptor Tyrosine Kinases", "descriptor_ui": "D018719", "major_topic": false }, { "descriptor": "Fluorescent Dyes", "descriptor_ui": "D005456", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Immunoconjugates", "descriptor_ui": "D018796", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Nanoparticles", "descriptor_ui": "D053758", "major_topic": false }, { "descriptor": "Neoplasms", "descriptor_ui": "D009369", "major_topic": false }, { "descriptor": "Trastuzumab", "descriptor_ui": "D000068878", "major_topic": false }, { "descriptor": "Tumor Cells, Cultured", "descriptor_ui": "D014407", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Jul 15", "date_precision": "day", "issue": "14", "normalized_date": "2021-07-15", "pages": "3970-3979", "proceedings_title": null, "publisher": "", "title": "Clinical cancer research : an official journal of the American Association for Cancer Research", "volume": "27", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Visualization of Intratumor Pharmacokinetics of [fam-] Trastuzumab Deruxtecan (DS-8201a) in HER2 Heterogeneous Model Using Phosphor-integrated Dots Imaging Analysis.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "While molecular oxygen is essential for aerobic organisms, its utilization is inseparably connected with generation of oxidative insults. To cope with the detrimental aspects, cells evolved antioxidative defense systems, and insufficient management of the oxidative insults underlies the pathogenesis of a wide range of diseases. A battery of genes for this antioxidative defense are regulated by the transcription factors nuclear factor-erythroid 2-like 1 and 2 (NRF1 and NRF2). While the regulatory steps for the activation of NRFs have been investigated with particular emphasis on nuclear translocation and proteosomal degradation, unknown redundancy may exist considering the indispensable nature of these defense systems. Here we unraveled that C-terminal binding protein 2 (CtBP2), a transcriptional cofactor with redox-sensing capability, is an obligate partner of NRFs. CtBP2 forms transcriptional complexes with NRF1 and NRF2 that is required to promote the expression of antioxidant genes in response to oxidative insults. Our findings illustrate a basis for understanding the transcriptional regulation of antioxidative defense systems that may be exploited therapeutically.", "classifications": [ { "id": "Miyamoto", "label": "Group Miyamoto", "parent": "Wakamoto", "type": "group" }, { "id": "Wakamoto", "label": "Team Wakamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Kenta", "last_name": "Kainoh", "name": null }, { "creator_type": "author", "first_name": "Ryo", "last_name": "Takano", "name": null }, { "creator_type": "author", "first_name": "Motohiro", "last_name": "Sekiya", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Takehito", "last_name": "Sugasawa", "name": null }, { "creator_type": "author", "first_name": "Yang", "last_name": "Ma", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Murayama", "name": null }, { "creator_type": "author", "first_name": "Yoko", "last_name": "Sugano", "name": null }, { "creator_type": "author", "first_name": "Yoshinori", "last_name": "Osaki", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Iwasaki", "name": null }, { "creator_type": "author", "first_name": "Yoshinori", "last_name": "Takeuchi", "name": null }, { "creator_type": "author", "first_name": "Naoya", "last_name": "Yahagi", "name": null }, { "creator_type": "author", "first_name": "Hiroaki", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Takafumi", "last_name": "Miyamoto", "name": null }, { "creator_type": "author", "first_name": "Yoshimi", "last_name": "Nakagawa", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Matsuzaka", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Shimano", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.bbrc.2021.05.069" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "34052660" } }, "mesh": [ { "descriptor": "Alcohol Oxidoreductases", "descriptor_ui": "D000429", "major_topic": false }, { "descriptor": "Amino Acid Sequence", "descriptor_ui": "D000595", "major_topic": false }, { "descriptor": "Antioxidants", "descriptor_ui": "D000975", "major_topic": false }, { "descriptor": "Co-Repressor Proteins", "descriptor_ui": "D056970", "major_topic": false }, { "descriptor": "Gene Expression Regulation", "descriptor_ui": "D005786", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "NF-E2-Related Factor 1", "descriptor_ui": "D051265", "major_topic": false }, { "descriptor": "NF-E2-Related Factor 2", "descriptor_ui": "D051267", "major_topic": false }, { "descriptor": "Oxidative Stress", "descriptor_ui": "D018384", "major_topic": false }, { "descriptor": "Protein Binding", "descriptor_ui": "D011485", "major_topic": false }, { "descriptor": "Transcription, Genetic", "descriptor_ui": "D014158", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Jul 12", "date_precision": "day", "issue": "", "normalized_date": "2021-07-12", "pages": "146-153", "proceedings_title": null, "publisher": "", "title": "Biochemical and biophysical research communications", "volume": "562", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "CtBP2 confers protection against oxidative stress through interactions with NRF1 and NRF2.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Multiciliated cells (MCCs) in tracheas generate mucociliary clearance through coordinated ciliary beating. Apical microtubules (MTs) play a crucial role in this process by organizing the planar cell polarity (PCP)-dependent orientation of ciliary basal bodies (BBs), for which the underlying molecular basis remains elusive. Herein, we found that the deficiency of Daple, a dishevelled-associating protein, in tracheal MCCs impaired the planar polarized apical MTs without affecting the core PCP proteins, causing significant defects in the BB orientation at the cell level but not the tissue level. Using live-cell imaging and ultra-high voltage electron microscope tomography, we found that the apical MTs accumulated and were stabilized by side-by-side association with one side of the apical junctional complex, to which Daple was localized. In vitro binding and single-molecule imaging revealed that Daple directly bound to, bundled, and stabilized MTs through its dimerization. These features convey a PCP-related molecular basis for the polarization of apical MTs, which coordinate ciliary beating in tracheal MCCs.", "classifications": [ { "id": "Ishihara", "label": "Group Ishihara", "parent": "Sawai", "type": "group" }, { "id": "Sawai", "label": "Team Sawai", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Shogo", "last_name": "Nakayama", "name": null }, { "creator_type": "author", "first_name": "Tomoki", "last_name": "Yano", "name": null }, { "creator_type": "author", "first_name": "Toshinori", "last_name": "Namba", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Konishi", "name": null }, { "creator_type": "author", "first_name": "Maki", "last_name": "Takagishi", "name": null }, { "creator_type": "author", "first_name": "Elisa", "last_name": "Herawati", "name": null }, { "creator_type": "author", "first_name": "Tomoki", "last_name": "Nishida", "name": null }, { "creator_type": "author", "first_name": "Yasuo", "last_name": "Imoto", "name": null }, { "creator_type": "author", "first_name": "Shuji", "last_name": "Ishihara", "name": null }, { "creator_type": "author", "first_name": "Masahide", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Ken'ya", "last_name": "Furuta", "name": null }, { "creator_type": "author", "first_name": "Kazuhiro", "last_name": "Oiwa", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Tamura", "name": null }, { "creator_type": "author", "first_name": "Sachiko", "last_name": "Tsukita", "name": null } ], "identifiers": { "doi": { "normalized": "10.1083/jcb.202010034" }, "pmcid": { "normalized": "PMC8094116" }, "pmid": { "normalized": "33929515" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Basal Bodies", "descriptor_ui": "D064652", "major_topic": false }, { "descriptor": "Carrier Proteins", "descriptor_ui": "D002352", "major_topic": false }, { "descriptor": "Cell Polarity", "descriptor_ui": "D016764", "major_topic": false }, { "descriptor": "Cilia", "descriptor_ui": "D002923", "major_topic": false }, { "descriptor": "Epithelial Cells", "descriptor_ui": "D004847", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Microtubules", "descriptor_ui": "D008870", "major_topic": false }, { "descriptor": "Mucociliary Clearance", "descriptor_ui": "D009079", "major_topic": false }, { "descriptor": "Trachea", "descriptor_ui": "D014132", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Jul 5", "date_precision": "day", "issue": "7", "normalized_date": "2021-07-05", "pages": "e202010034", "proceedings_title": null, "publisher": "", "title": "The Journal of cell biology", "volume": "220", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Planar cell polarity induces local microtubule bundling for coordinated ciliary beating.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Injury in adult tissue generally reactivates developmental programs to foster regeneration, but it is not known whether this paradigm applies to growing tissue. Here, by employing blisters, we show that epidermal wounds heal at the expense of skin development. The regenerated epidermis suppresses the expression of tissue morphogenesis genes accompanied by delayed hair follicle (HF) growth. Lineage tracing experiments, cell proliferation dynamics, and mathematical modeling reveal that the progeny of HF junctional zone stem cells, which undergo a morphological transformation, repair the blisters while not promoting HF development. In contrast, the contribution of interfollicular stem cell progeny to blister healing is small. These findings demonstrate that HF development can be sacrificed for the sake of epidermal wound regeneration. Our study elucidates the key cellular mechanism of wound healing in skin blistering diseases.", "classifications": [ { "id": "Nagayama", "label": "Group Nagayama", "parent": "Fujiwara", "type": "group" }, { "id": "Fujiwara", "label": "Team Fujiwara", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yu", "last_name": "Fujimura", "name": null }, { "creator_type": "author", "first_name": "Mika", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Kota", "last_name": "Ohno", "name": null }, { "creator_type": "author", "first_name": "Yasuaki", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Shota", "last_name": "Takashima", "name": null }, { "creator_type": "author", "first_name": "Hideki", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Hideyuki", "last_name": "Kosumi", "name": null }, { "creator_type": "author", "first_name": "Yunan", "last_name": "Wang", "name": null }, { "creator_type": "author", "first_name": "Yosuke", "last_name": "Mai", "name": null }, { "creator_type": "author", "first_name": "Andrea", "last_name": "Lauria", "name": null }, { "creator_type": "author", "first_name": "Valentina", "last_name": "Proserpio", "name": null }, { "creator_type": "author", "first_name": "Hideyuki", "last_name": "Ujiie", "name": null }, { "creator_type": "author", "first_name": "Hiroaki", "last_name": "Iwata", "name": null }, { "creator_type": "author", "first_name": "Wataru", "last_name": "Nishie", "name": null }, { "creator_type": "author", "first_name": "Masaharu", "last_name": "Nagayama", "name": null }, { "creator_type": "author", "first_name": "Salvatore", "last_name": "Oliviero", "name": null }, { "creator_type": "author", "first_name": "Giacomo", "last_name": "Donati", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Shimizu", "name": null }, { "creator_type": "author", "first_name": "Ken", "last_name": "Natsuga", "name": null } ], "identifiers": { "doi": { "normalized": "10.15252/embr.202050882" }, "pmcid": { "normalized": "PMC8256293" }, "pmid": { "normalized": "34085753" } }, "mesh": [ { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Blister", "descriptor_ui": "D001768", "major_topic": true }, { "descriptor": "Epidermal Cells", "descriptor_ui": "D000078404", "major_topic": false }, { "descriptor": "Epidermis", "descriptor_ui": "D004817", "major_topic": false }, { "descriptor": "Hair Follicle", "descriptor_ui": "D018859", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Skin", "descriptor_ui": "D012867", "major_topic": false }, { "descriptor": "Stem Cells", "descriptor_ui": "D013234", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Jul 5", "date_precision": "day", "issue": "7", "normalized_date": "2021-07-05", "pages": "e50882", "proceedings_title": null, "publisher": "", "title": "EMBO reports", "volume": "22", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Hair follicle stem cell progeny heal blisters while pausing skin development.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yuki", "last_name": "Takeyasu", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Noriko", "last_name": "Motoi", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Teishikata", "name": null }, { "creator_type": "author", "first_name": "Midori", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Yuji", "last_name": "Matsumoto", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Shinno", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Okuma", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Goto", "name": null }, { "creator_type": "author", "first_name": "Hidehito", "last_name": "Horinouchi", "name": null }, { "creator_type": "author", "first_name": "Hiroki", "last_name": "Kakishima", "name": null }, { "creator_type": "author", "first_name": "Takaaki", "last_name": "Tsuchida", "name": null }, { "creator_type": "author", "first_name": "Noboru", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Yuichiro", "last_name": "Ohe", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null } ], "identifiers": { "doi": { "normalized": "10.1093/jjco/hyab092" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "34100088" } }, "mesh": [], "publication": { "conference_name": null, "date": "2021 Jul 1", "date_precision": "day", "issue": "7", "normalized_date": "2021-07-01", "pages": "1183", "proceedings_title": null, "publisher": "", "title": "Japanese journal of clinical oncology", "volume": "51", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Corrigendum to: Feasibility of next-generation sequencing (Oncomine DX Target Test) for the screening of oncogenic mutations in advanced non-small-cell lung cancer patients.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: The Oncomine Dx Target Test based on next-generation sequencing has been approved for the screening of oncogenic mutations in advanced non-small-cell lung cancer patients. METHODS: We assessed the tissue sample factors that affect the success rate of Oncomine Dx Target Test companion diagnostics and the feasibility of using biopsy specimens for Oncomine Dx Target Test companion diagnostics in advanced non-small-cell lung cancer patients. RESULTS: Ninety-nine biopsy samples were subjected to genetic testing using the Oncomine Dx Target Test companion diagnostics to detect v-raf murine sarcoma viral oncogene homologue B1 mutations (Cohort 1), and 136 biopsy samples were examined using Oncomine Dx Target Test companion diagnostics for the detection of multiple oncogenic mutations (Cohort 2) between July 2018 and April 2020. We retrospectively collected clinical and pathological data, including tissue size and tumour cell content. The success rate was 77% (76/99) in Cohort 1 and 93% (127/136) in Cohort 2. In Cohort 1, the success rate was significantly associated with the tumour cell content: the success rate was 63% for samples with a tumour cell content of <20%, whereas it was 83% for samples with a tumour cell content of 20% or higher (P = 0.0446). The tissue size also affected the success rate: a success rate of 57% was obtained for tissue sizes <4 mm2, whereas a success rate of 95% was obtained for tissue sizes of 4 mm2 or larger (P < 0.0001). In Cohort 2, the success rate was 100% when tumour specimens with a tissue size of 4 mm2 or larger were used. CONCLUSIONS: Tissue size and tumour cell content were significantly associated with the success rate of Oncomine Dx Target Test companion diagnostics.", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yuki", "last_name": "Takeyasu", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Noriko", "last_name": "Motoi", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Teishikata", "name": null }, { "creator_type": "author", "first_name": "Midori", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Yuji", "last_name": "Matsumoto", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Shinno", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Okuma", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Goto", "name": null }, { "creator_type": "author", "first_name": "Hidehito", "last_name": "Horinouchi", "name": null }, { "creator_type": "author", "first_name": "Hiroki", "last_name": "Kakishima", "name": null }, { "creator_type": "author", "first_name": "Takaaki", "last_name": "Tsuchida", "name": null }, { "creator_type": "author", "first_name": "Noboru", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Yuichiro", "last_name": "Ohe", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null } ], "identifiers": { "doi": { "normalized": "10.1093/jjco/hyab059" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "33881137" } }, "mesh": [ { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Aged, 80 and over", "descriptor_ui": "D000369", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Carcinoma, Non-Small-Cell Lung", "descriptor_ui": "D002289", "major_topic": false }, { "descriptor": "Early Detection of Cancer", "descriptor_ui": "D055088", "major_topic": false }, { "descriptor": "Feasibility Studies", "descriptor_ui": "D005240", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Genetic Testing", "descriptor_ui": "D005820", "major_topic": false }, { "descriptor": "High-Throughput Nucleotide Sequencing", "descriptor_ui": "D059014", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Lung Neoplasms", "descriptor_ui": "D008175", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mass Screening", "descriptor_ui": "D008403", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": false }, { "descriptor": "Retrospective Studies", "descriptor_ui": "D012189", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Jul 1", "date_precision": "day", "issue": "7", "normalized_date": "2021-07-01", "pages": "1114-1122", "proceedings_title": null, "publisher": "", "title": "Japanese journal of clinical oncology", "volume": "51", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Feasibility of next-generation sequencing (Oncomine DX Target Test) for the screening of oncogenic mutations in advanced non-small-cell lung cancer patients.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Deoxyribonucleotide biosynthesis from ribonucleotides supports the growth of active cancer cells by producing building blocks for DNA. Although ribonucleotide reductase (RNR) is known to catalyze the rate-limiting step of de novo deoxyribonucleotide triphosphate (dNTP) synthesis, the biological function of the RNR large subunit (RRM1) in small-cell lung carcinoma (SCLC) remains unclear. In this study, we established siRNA-transfected SCLC cell lines to investigate the anticancer effect of silencing RRM1 gene expression. We found that RRM1 is required for the full growth of SCLC cells both in vitro and in vivo. In particular, the deletion of RRM1 induced a DNA damage response in SCLC cells and decreased the number of cells with S phase cell cycle arrest. We also elucidated the overall changes in the metabolic profile of SCLC cells caused by RRM1 deletion. Together, our findings reveal a relationship between the deoxyribonucleotide biosynthesis axis and key metabolic changes in SCLC, which may indicate a possible link between tumor growth and the regulation of deoxyribonucleotide metabolism in SCLC.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Ami", "last_name": "Maruyama", "name": null }, { "creator_type": "author", "first_name": "Yuzo", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Joji", "last_name": "Nakayama", "name": null }, { "creator_type": "author", "first_name": "Junko", "last_name": "Murai", "name": null }, { "creator_type": "author", "first_name": "Takamasa", "last_name": "Ishikawa", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Hideki", "last_name": "Makinoshima", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41598-021-92948-9" }, "pmcid": { "normalized": "PMC8242079" }, "pmid": { "normalized": "34188151" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Cell Proliferation", "descriptor_ui": "D049109", "major_topic": true }, { "descriptor": "Deoxyribonucleotides", "descriptor_ui": "D003854", "major_topic": false }, { "descriptor": "DNA Damage", "descriptor_ui": "D004249", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Lung Neoplasms", "descriptor_ui": "D008175", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Nude", "descriptor_ui": "D008819", "major_topic": false }, { "descriptor": "Neoplasm Proteins", "descriptor_ui": "D009363", "major_topic": false }, { "descriptor": "Ribonucleoside Diphosphate Reductase", "descriptor_ui": "D012262", "major_topic": false }, { "descriptor": "Small Cell Lung Carcinoma", "descriptor_ui": "D055752", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Jun 29", "date_precision": "day", "issue": "1", "normalized_date": "2021-06-29", "pages": "13474", "proceedings_title": null, "publisher": "", "title": "Scientific reports", "volume": "11", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "De novo deoxyribonucleotide biosynthesis regulates cell growth and tumor progression in small-cell lung carcinoma.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Muscle energetics reflects the ability of myosin motors to convert chemical energy into mechanical energy. How this process takes place remains one of the most elusive questions in the field. Here, we combined experimental measurements of in vitro sliding velocity based on DNA-origami built filaments carrying myosins with different lever arm length and Monte Carlo simulations based on a model which accounts for three basic components: (i) the geometrical hindrance, (ii) the mechano-sensing mechanism, and (iii) the biased kinetics for stretched or compressed motors. The model simulations showed that the geometrical hindrance due to acto-myosin spatial mismatching and the preferential detachment of compressed motors are synergic in generating the rapid increase in the ATP-ase rate from isometric to moderate velocities of contraction, thus acting as an energy-conservation strategy in muscle contraction. The velocity measurements on a DNA-origami filament that preserves the motors' distribution showed that geometrical hindrance and biased detachment generate a non-zero sliding velocity even without rotation of the myosin lever-arm, which is widely recognized as the basic event in muscle contraction. Because biased detachment is a mechanism for the rectification of thermal fluctuations, in the Brownian-ratchet framework, we predict that it requires a non-negligible amount of energy to preserve the second law of thermodynamics. Taken together, our theoretical and experimental results elucidate less considered components in the chemo-mechanical energy transduction in muscle.", "classifications": [ { "id": "Iwaki", "label": "Group Iwaki", "parent": "Toyoshima", "type": "group" }, { "id": "Toyoshima", "label": "Team Toyoshima", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Lorenzo", "last_name": "Marcucci", "name": null }, { "creator_type": "author", "first_name": "Hiroki", "last_name": "Fukunaga", "name": null }, { "creator_type": "author", "first_name": "Toshio", "last_name": "Yanagida", "name": null }, { "creator_type": "author", "first_name": "Mitsuhiro", "last_name": "Iwaki", "name": null } ], "identifiers": { "doi": { "normalized": "10.3390/ijms22137037" }, "pmcid": { "normalized": "PMC8269045" }, "pmid": { "normalized": "34210098" } }, "mesh": [ { "descriptor": "Actomyosin", "descriptor_ui": "D000205", "major_topic": false }, { "descriptor": "Adenosine Triphosphatases", "descriptor_ui": "D000251", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Kinetics", "descriptor_ui": "D007700", "major_topic": false }, { "descriptor": "Models, Biological", "descriptor_ui": "D008954", "major_topic": false }, { "descriptor": "Monte Carlo Method", "descriptor_ui": "D009010", "major_topic": false }, { "descriptor": "Muscle Contraction", "descriptor_ui": "D009119", "major_topic": false }, { "descriptor": "Muscles", "descriptor_ui": "D009132", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Jun 29", "date_precision": "day", "issue": "13", "normalized_date": "2021-06-29", "pages": "7037", "proceedings_title": null, "publisher": "", "title": "International journal of molecular sciences", "volume": "22", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "The Synergic Role of Actomyosin Architecture and Biased Detachment in Muscle Energetics: Insights in Cross Bridge Mechanism Beyond the Lever-Arm Swing.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Epithelial-mesenchymal transition (EMT)-a fundamental process in embryogenesis and wound healing-promotes tumor metastasis and resistance to chemotherapy. While studies have identified signaling components and transcriptional factors responsible in the TGF-beta-dependent EMT, whether and how intracellular metabolism is integrated with EMT remains to be fully elucidated. Here, we showed that TGF-beta induces reprogramming of intracellular amino acid metabolism, which is necessary to promote EMT in non-small cell lung cancer cells. Combined metabolome and transcriptome analysis identified prolyl 4-hydroxylase alpha3 (P4HA3), an enzyme implicated in cancer metabolism, to be upregulated during TGF-beta stimulation. Further, knockdown of P4HA3 diminished TGF-beta-dependent changes in amino acids, EMT, and tumor metastasis. Conversely, manipulation of extracellular amino acids induced EMT-like responses without TGF-beta stimulation. These results suggest a previously unappreciated requirement for the reprogramming of amino acid metabolism via P4HA3 for TGF-beta-dependent EMT and implicate a P4HA3 inhibitor as a potential therapeutic agent for cancer.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Fumie", "last_name": "Nakasuka", "name": null }, { "creator_type": "author", "first_name": "Sho", "last_name": "Tabata", "name": null }, { "creator_type": "author", "first_name": "Takeharu", "last_name": "Sakamoto", "name": null }, { "creator_type": "author", "first_name": "Akiyoshi", "last_name": "Hirayama", "name": null }, { "creator_type": "author", "first_name": "Hiromichi", "last_name": "Ebi", "name": null }, { "creator_type": "author", "first_name": "Tadaaki", "last_name": "Yamada", "name": null }, { "creator_type": "author", "first_name": "Ko", "last_name": "Umetsu", "name": null }, { "creator_type": "author", "first_name": "Maki", "last_name": "Ohishi", "name": null }, { "creator_type": "author", "first_name": "Ayano", "last_name": "Ueno", "name": null }, { "creator_type": "author", "first_name": "Hisatsugu", "last_name": "Goto", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Sugimoto", "name": null }, { "creator_type": "author", "first_name": "Yasuhiko", "last_name": "Nishioka", "name": null }, { "creator_type": "author", "first_name": "Yasuhiro", "last_name": "Yamada", "name": null }, { "creator_type": "author", "first_name": "Masaru", "last_name": "Tomita", "name": null }, { "creator_type": "author", "first_name": "Atsuo T.", "last_name": "Sasaki", "name": null }, { "creator_type": "author", "first_name": "Seiji", "last_name": "Yano", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s42003-021-02323-7" }, "pmcid": { "normalized": "PMC8225889" }, "pmid": { "normalized": "34168290" } }, "mesh": [ { "descriptor": "Amino Acids", "descriptor_ui": "D000596", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Carcinoma, Non-Small-Cell Lung", "descriptor_ui": "D002289", "major_topic": false }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Epithelial-Mesenchymal Transition", "descriptor_ui": "D058750", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Gene Expression Profiling", "descriptor_ui": "D020869", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Lung Neoplasms", "descriptor_ui": "D008175", "major_topic": false }, { "descriptor": "Metabolomics", "descriptor_ui": "D055432", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Procollagen-Proline Dioxygenase", "descriptor_ui": "D011393", "major_topic": false }, { "descriptor": "Transforming Growth Factor beta", "descriptor_ui": "D016212", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Jun 24", "date_precision": "day", "issue": "1", "normalized_date": "2021-06-24", "pages": "782", "proceedings_title": null, "publisher": "", "title": "Communications biology", "volume": "4", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "TGF-beta-dependent reprogramming of amino acid metabolism induces epithelial-mesenchymal transition in non-small cell lung cancers.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The skin barrier is provided by the organized multi-layer structure of epidermal cells, which is dynamically maintained by a continuous supply of cells from the basal layer. The epidermal homeostasis can be disrupted by various skin diseases, which often cause morphological changes not only in the epidermis but in the dermis. We present a three-dimensional agent-based computational model of the epidermis that takes into account the deformability of the dermis. Our model can produce a stable epidermal structure with well-organized layers. We show that its stability depends on the cell supply rate from the basal layer. Modeling the morphological change of the dermis also enables us to investigate how the stiffness of the dermis affects the structure and barrier functions of the epidermis. Besides, we show that our model can simulate the formation of a corn (clavus) by assuming hyperproliferation and rapid differentiation. We also provide experimental data for human corn, which supports the model assumptions and the simulation result.", "classifications": [ { "id": "Nagayama", "label": "Group Nagayama", "parent": "Fujiwara", "type": "group" }, { "id": "Fujiwara", "label": "Team Fujiwara", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Kota", "last_name": "Ohno", "name": null }, { "creator_type": "author", "first_name": "Yasuaki", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Masaaki", "last_name": "Uesaka", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Gotoda", "name": null }, { "creator_type": "author", "first_name": "Mitsuhiro", "last_name": "Denda", "name": null }, { "creator_type": "author", "first_name": "Hideyuki", "last_name": "Kosumi", "name": null }, { "creator_type": "author", "first_name": "Mika", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Ken", "last_name": "Natsuga", "name": null }, { "creator_type": "author", "first_name": "Masaharu", "last_name": "Nagayama", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41598-021-92540-1" }, "pmcid": { "normalized": "PMC8225835" }, "pmid": { "normalized": "34168195" } }, "mesh": [ { "descriptor": "Computer Simulation", "descriptor_ui": "D003198", "major_topic": false }, { "descriptor": "Dermis", "descriptor_ui": "D020405", "major_topic": false }, { "descriptor": "Epidermis", "descriptor_ui": "D004817", "major_topic": false }, { "descriptor": "Homeostasis", "descriptor_ui": "D006706", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Skin Diseases", "descriptor_ui": "D012871", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Jun 24", "date_precision": "day", "issue": "1", "normalized_date": "2021-06-24", "pages": "13234", "proceedings_title": null, "publisher": "", "title": "Scientific reports", "volume": "11", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "A computational model of the epidermis with the deformable dermis and its application to skin diseases.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Hydroxide anion transport is essential for alkaline fuel cells, but hydroxide anion has an inherently low conductivity owing to its small diffusion coefficient and high mass. Ordered open channels found in covalent organic frameworks are promising as pathways to enable hydroxide anion transport, but this remains to be explored. Here we report designed synthesis of anionic covalent organic frameworks that promote hydroxide anion transport across the one-dimensional channels. Engineering cationic chains with imidazolium termini onto the pore walls self-assembles a supramolecular interface of single-file hydroxide anion chains in the channels. The frameworks facilitate hydroxide anion transport to achieve an exceptional conductivity of 1.53 x 10(-2) S cm(-1) at 80 degrees C, which is 2-6 orders of magnitude higher than those of linear polymers and other porous frameworks. Impedance spectroscopy at different temperatures and studies on deuterated samples reveal that hydroxide anions transport via a proton-exchange hopping mechanism. These results open a way to design framework materials for energy conversions via engineering an anionic interface.", "classifications": [ { "id": "Hijikata", "label": "Group Hijikata", "parent": "Tsuchiya", "type": "group" }, { "id": "Tsuchiya", "label": "Team Tsuchiya", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Shanshan", "last_name": "Tao", "name": null }, { "creator_type": "author", "first_name": "Hong", "last_name": "Xu", "name": null }, { "creator_type": "author", "first_name": "Qing", "last_name": "Xu", "name": null }, { "creator_type": "author", "first_name": "Yuh", "last_name": "Hijikata", "name": null }, { "creator_type": "author", "first_name": "Qiuhong", "last_name": "Jiang", "name": null }, { "creator_type": "author", "first_name": "Stephan", "last_name": "Irle", "name": null }, { "creator_type": "author", "first_name": "Donglin", "last_name": "Jiang", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/jacs.1c03268" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "34110806" } }, "mesh": [], "publication": { "conference_name": null, "date": "2021 Jun 23", "date_precision": "day", "issue": "24", "normalized_date": "2021-06-23", "pages": "8970-8975", "proceedings_title": null, "publisher": "", "title": "Journal of the American Chemical Society", "volume": "143", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Hydroxide Anion Transport in Covalent Organic Frameworks.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Reaction design in asymmetric catalysis has traditionally been predicated on a structurally robust scaffold in both substrates and catalysts, to reduce the number of possible diastereomeric transition states. Herein, we present the stereochemical dynamics in the Ni(II)-catalyzed diastereoconvergent (3 + 2) cycloadditions of isomerizable nitrile-conjugated nitrones with alpha-keto ester enolates. Even in the presence of multiple equilibrating species, the catalytic protocol displays a wide substrate scope to access a range of CN-containing building blocks bearing adjacent stereocenters with high enantio- and diastereoselectivities. Our computational investigations suggest that the enantioselectivity is governed in the deprotonation process to form (Z)-Ni-enolates, while the unique syn addition is mainly controlled by weak noncovalent bonding interactions between the nitrone and ligand.", "classifications": [ { "id": "Sodeoka", "label": "Group Sodeoka", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Tetsuya", "last_name": "Ezawa", "name": null }, { "creator_type": "author", "first_name": "Yoshihiro", "last_name": "Sohtome", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Hashizume", "name": null }, { "creator_type": "author", "first_name": "Masaya", "last_name": "Adachi", "name": null }, { "creator_type": "author", "first_name": "Mai", "last_name": "Akakabe", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Koshino", "name": null }, { "creator_type": "author", "first_name": "Mikiko", "last_name": "Sodeoka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/jacs.1c02833" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "34107685" } }, "mesh": [], "publication": { "conference_name": null, "date": "2021 Jun 23", "date_precision": "day", "issue": "24", "normalized_date": "2021-06-23", "pages": "9094-9104", "proceedings_title": null, "publisher": "", "title": "Journal of the American Chemical Society", "volume": "143", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Dynamics in Catalytic Asymmetric Diastereoconvergent (3 + 2) Cycloadditions with Isomerizable Nitrones and alpha-Keto Ester Enolates.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Developing neurons initially form excessive neurites and then remodel them based on molecular cues and neuronal activity. Developing mitral cells in the olfactory bulb initially extend multiple primary dendrites. They then stabilize single primary dendrites while eliminating others. However, the mechanisms underlying selective dendrite remodeling remain elusive. Using CRISPR-Cas9-based knockout screening combined with in utero electroporation, we identify BMPR-2 as a key regulator for selective dendrite stabilization. Bmpr2 knockout and its rescue experiments show that BMPR-2 inhibits LIMK without ligands and thereby permits dendrite destabilization. In contrast, the overexpression of antagonists and agonists indicates that ligand-bound BMPR-2 stabilizes dendrites, most likely by releasing LIMK. Using genetic and FRET imaging experiments, we demonstrate that free LIMK is activated by NMDARs via Rac1, facilitating dendrite stabilization through F-actin formation. Thus, the selective stabilization of primary dendrites is ensured by concomitant inputs of BMP ligands and neuronal activity.", "classifications": [ { "id": "Imai", "label": "Group Imai", "parent": "Enomoto", "type": "group" }, { "id": "Enomoto", "label": "Team Enomoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Shuhei", "last_name": "Aihara", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Fujimoto", "name": null }, { "creator_type": "author", "first_name": "Richi", "last_name": "Sakaguchi", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Imai", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.celrep.2021.109276" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "34161760" } }, "mesh": [ { "descriptor": "Actin Cytoskeleton", "descriptor_ui": "D008841", "major_topic": false }, { "descriptor": "Actin Depolymerizing Factors", "descriptor_ui": "D051339", "major_topic": false }, { "descriptor": "Actins", "descriptor_ui": "D000199", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Bone Morphogenetic Protein Receptors, Type II", "descriptor_ui": "D052006", "major_topic": false }, { "descriptor": "Bone Morphogenetic Proteins", "descriptor_ui": "D019485", "major_topic": false }, { "descriptor": "Dendrites", "descriptor_ui": "D003712", "major_topic": false }, { "descriptor": "Glutamic Acid", "descriptor_ui": "D018698", "major_topic": false }, { "descriptor": "Ligands", "descriptor_ui": "D008024", "major_topic": false }, { "descriptor": "Lim Kinases", "descriptor_ui": "D054461", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Olfactory Bulb", "descriptor_ui": "D009830", "major_topic": false }, { "descriptor": "p21-Activated Kinases", "descriptor_ui": "D054462", "major_topic": false }, { "descriptor": "Protein Domains", "descriptor_ui": "D000072417", "major_topic": false }, { "descriptor": "rac1 GTP-Binding Protein", "descriptor_ui": "D020830", "major_topic": false }, { "descriptor": "Receptors, N-Methyl-D-Aspartate", "descriptor_ui": "D016194", "major_topic": false }, { "descriptor": "Structure-Activity Relationship", "descriptor_ui": "D013329", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Jun 22", "date_precision": "day", "issue": "12", "normalized_date": "2021-06-22", "pages": "109276", "proceedings_title": null, "publisher": "", "title": "Cell reports", "volume": "35", "year": 2021 }, "ssbd": { "database": [], "repository": [ "ssbd-repos-000169" ] }, "title": "BMPR-2 gates activity-dependent stabilization of primary dendrites during mitral cell remodeling.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Recent advancements in tissue clearing technologies have offered unparalleled opportunities for researchers to explore the whole mouse brain at cellular resolution. With the expansion of this experimental technique, however, a scalable and easy-to-use computational tool is in demand to effectively analyze and integrate whole-brain mapping datasets. To that end, here we present CUBIC-Cloud, a cloud-based framework to quantify, visualize, and integrate mouse brain data. CUBIC-Cloud is a fully automated system where users can upload their whole-brain data, run analyses, and publish the results. We demonstrate the generality of CUBIC-Cloud by a variety of applications. First, we investigated the brain-wide distribution of five cell types. Second, we quantified Abeta plaque deposition in Alzheimer's disease model mouse brains. Third, we reconstructed a neuronal activity profile under LPS-induced inflammation by c-Fos immunostaining. Last, we show brain-wide connectivity mapping by pseudotyped rabies virus. Together, CUBIC-Cloud provides an integrative platform to advance scalable and collaborative whole-brain mapping.", "classifications": [ { "id": "Miyamichi", "label": "Group Miyamichi", "parent": "Enomoto", "type": "group" }, { "id": "Enomoto", "label": "Team Enomoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Tomoyuki", "last_name": "Mano", "name": null }, { "creator_type": "author", "first_name": "Ken", "last_name": "Murata", "name": null }, { "creator_type": "author", "first_name": "Kazuhiro", "last_name": "Kon", "name": null }, { "creator_type": "author", "first_name": "Chika", "last_name": "Shimizu", "name": null }, { "creator_type": "author", "first_name": "Hiroaki", "last_name": "Ono", "name": null }, { "creator_type": "author", "first_name": "Shoi", "last_name": "Shi", "name": null }, { "creator_type": "author", "first_name": "Rikuhiro G.", "last_name": "Yamada", "name": null }, { "creator_type": "author", "first_name": "Kazunari", "last_name": "Miyamichi", "name": null }, { "creator_type": "author", "first_name": "Etsuo A.", "last_name": "Susaki", "name": null }, { "creator_type": "author", "first_name": "Kazushige", "last_name": "Touhara", "name": null }, { "creator_type": "author", "first_name": "Hiroki R.", "last_name": "Ueda", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.crmeth.2021.100038" }, "pmcid": { "normalized": "PMC9017177" }, "pmid": { "normalized": "35475238" } }, "mesh": [ { "descriptor": "Alzheimer Disease", "descriptor_ui": "D000544", "major_topic": true }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Brain", "descriptor_ui": "D001921", "major_topic": true }, { "descriptor": "Brain Mapping", "descriptor_ui": "D001931", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Jun 21", "date_precision": "day", "issue": "2", "normalized_date": "2021-06-21", "pages": "100038", "proceedings_title": null, "publisher": "", "title": "Cell reports methods", "volume": "1", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "CUBIC-Cloud provides an integrative computational framework toward community-driven whole-mouse-brain mapping.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "PURPOSE: This study aimed to compare patients with early oral cavity squamous cell carcinoma (OCSCC) (tumor category [T] 1-2, node-negative, and no distant metastasis) treated with traditional elective neck dissection (ND) with those managed by sentinel lymph node biopsy (SLNB) using survival and neck function and complications as end points. METHODS: Sixteen institutions in Japan participated in the study (trial registration number: UMIN000006510). Patients of age >/= 18 years with histologically confirmed, previously untreated OCSCC (Union for International Cancer Control TNM Classification of Malignant Tumors 7th edition T1-2, node-negative no distant metastasis), with >/= 4 mm (T1) depth of invasion, were randomly assigned to undergo standard selective ND (ND group; n = 137) or SLNB-navigated ND (SLNB group; n = 134). The primary end point was the 3-year overall survival rate, with a 12% noninferiority margin; secondary end points included postoperative neck functionality and complications and 3-year disease-free survival. Sentinel lymph nodes underwent intraoperative multislice frozen section analyses for the diagnosis. Patients with positive sentinel lymph nodes underwent either one-stage or second-look ND. RESULTS: Pathologic metastasis-positive nodes were observed in 24.8% (34 of 137) and 33.6% (46 of 134) of patients in the ND and SLNB groups, respectively (P = .190). The 3-year overall survival in the SLNB group (87.9%; lower limit of one-sided 95% CI, 82.4) was noninferior to that in the ND group (86.6%; lower limit 95% CI, 80.9; P for noninferiority < .001). The 3-year disease-free survival rate was 78.7% (lower limit 95% CI, 72.1) and 81.3% (75.0) in the SLNB and ND groups, respectively (P for noninferiority < .001). The scores of neck functionality in the SLNB group were significantly better than those in the ND group. CONCLUSION: SLNB-navigated ND may replace elective ND without a survival disadvantage and reduce postoperative neck disability in patients with early-stage OCSCC.", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yasuhisa", "last_name": "Hasegawa", "name": null }, { "creator_type": "author", "first_name": "Kiyoaki", "last_name": "Tsukahara", "name": null }, { "creator_type": "author", "first_name": "Seiichi", "last_name": "Yoshimoto", "name": null }, { "creator_type": "author", "first_name": "Kouki", "last_name": "Miura", "name": null }, { "creator_type": "author", "first_name": "Junkichi", "last_name": "Yokoyama", "name": null }, { "creator_type": "author", "first_name": "Shigeru", "last_name": "Hirano", "name": null }, { "creator_type": "author", "first_name": "Hirokazu", "last_name": "Uemura", "name": null }, { "creator_type": "author", "first_name": "Masashi", "last_name": "Sugasawa", "name": null }, { "creator_type": "author", "first_name": "Tomokazu", "last_name": "Yoshizaki", "name": null }, { "creator_type": "author", "first_name": "Akihiro", "last_name": "Homma", "name": null }, { "creator_type": "author", "first_name": "Kazuaki", "last_name": "Chikamatsu", "name": null }, { "creator_type": "author", "first_name": "Mikio", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Akihiro", "last_name": "Shiotani", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Matsuzuka", "name": null }, { "creator_type": "author", "first_name": "Naoyuki", "last_name": "Kohno", "name": null }, { "creator_type": "author", "first_name": "Masakazu", "last_name": "Miyazaki", "name": null }, { "creator_type": "author", "first_name": "Isao", "last_name": "Oze", "name": null }, { "creator_type": "author", "first_name": "Keitaro", "last_name": "Matsuo", "name": null }, { "creator_type": "author", "first_name": "Shigeru", "last_name": "Kosuda", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null } ], "identifiers": { "doi": { "normalized": "10.1200/jco.20.03637" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "33877855" } }, "mesh": [ { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Aged, 80 and over", "descriptor_ui": "D000369", "major_topic": false }, { "descriptor": "Disease-Free Survival", "descriptor_ui": "D018572", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Lymph Node Excision", "descriptor_ui": "D008197", "major_topic": false }, { "descriptor": "Lymph Nodes", "descriptor_ui": "D008198", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Mouth Neoplasms", "descriptor_ui": "D009062", "major_topic": false }, { "descriptor": "Neoplasm Recurrence, Local", "descriptor_ui": "D009364", "major_topic": false }, { "descriptor": "Sentinel Lymph Node", "descriptor_ui": "D000071036", "major_topic": false }, { "descriptor": "Sentinel Lymph Node Biopsy", "descriptor_ui": "D021701", "major_topic": false }, { "descriptor": "Squamous Cell Carcinoma of Head and Neck", "descriptor_ui": "D000077195", "major_topic": false }, { "descriptor": "Young Adult", "descriptor_ui": "D055815", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Jun 20", "date_precision": "day", "issue": "18", "normalized_date": "2021-06-20", "pages": "2025-2036", "proceedings_title": null, "publisher": "", "title": "Journal of clinical oncology : official journal of the American Society of Clinical Oncology", "volume": "39", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Neck Dissections Based on Sentinel Lymph Node Navigation Versus Elective Neck Dissections in Early Oral Cancers: A Randomized, Multicenter, and Noninferiority Trial.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Aims: Persulfides and other reactive sulfur species are endogenously produced in large amounts in vivo and participate in multiple cellular functions underlying physiological and pathological conditions. In the current study, we aimed to develop an ideal alkylating agent for use in sulfur metabolomics, particularly targeting persulfides and other reactive sulfur species, with minimal artifactual decomposition. Results: We synthesized a tyrosine-based iodoacetamide derivative, N-iodoacetyl l-tyrosine methyl ester (TME-IAM), which reacts with the thiol residue of cysteine identically to that of beta-(4-hydroxyphenyl)ethyl iodoacetamide (HPE-IAM), a commercially available reagent. Our previous study revealed that although various electrophilic alkylating agents readily decomposed polysulfides, HPE-IAM exceptionally stabilized the polysulfides by inhibiting their alkaline hydrolysis. The newly synthesized TME-IAM stabilizes oxidized glutathione tetrasulfide more efficiently than other alkylating agents, including HPE-IAM, iodoacetamide, and monobromobimane. In fact, our quantitative sulfur-related metabolome analysis showed that TME-IAM is a more efficient trapping agent for endogenous persulfides/polysulfides containing a larger number of sulfur atoms in mouse liver and brain tissues compared with HPE-IAM. Innovation and Conclusions: We developed a novel iodoacetamide derivative, which is the most ideal reagent developed to date for detecting endogenous persulfides/polysulfides formed in biological samples, such as cultured cells, tissues, and plasma. This new probe may be useful for investigating the unique chemical properties of reactive persulfides, thereby enabling identification of novel reactive sulfur metabolites that remain unidentified because of their instability, and thus can be applied in high-precision sulfur metabolomics in redox biology and medicine. We did not perform any clinical experiments in this study. Antioxid. Redox Signal. 34, 1407-1419.", "classifications": [ { "id": "Akaike", "label": "Group Akaike", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Shingo", "last_name": "Kasamatsu", "name": null }, { "creator_type": "author", "first_name": "Tomoaki", "last_name": "Ida", "name": null }, { "creator_type": "author", "first_name": "Taisei", "last_name": "Koga", "name": null }, { "creator_type": "author", "first_name": "Kosho", "last_name": "Asada", "name": null }, { "creator_type": "author", "first_name": "Hozumi", "last_name": "Motohashi", "name": null }, { "creator_type": "author", "first_name": "Hideshi", "last_name": "Ihara", "name": null }, { "creator_type": "author", "first_name": "Takaaki", "last_name": "Akaike", "name": null } ], "identifiers": { "doi": { "normalized": "10.1089/ars.2020.8073" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "33198504" } }, "mesh": [ { "descriptor": "Acetamides", "descriptor_ui": "D000081", "major_topic": false }, { "descriptor": "Alkylating Agents", "descriptor_ui": "D000477", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Chromatography, Liquid", "descriptor_ui": "D002853", "major_topic": false }, { "descriptor": "HEK293 Cells", "descriptor_ui": "D057809", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Iodoacetamide", "descriptor_ui": "D007460", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mass Spectrometry", "descriptor_ui": "D013058", "major_topic": false }, { "descriptor": "Metabolomics", "descriptor_ui": "D055432", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Oxidation-Reduction", "descriptor_ui": "D010084", "major_topic": false }, { "descriptor": "Reactive Nitrogen Species", "descriptor_ui": "D026361", "major_topic": false }, { "descriptor": "Sulfides", "descriptor_ui": "D013440", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Jun 20", "date_precision": "day", "issue": "18", "normalized_date": "2021-06-20", "pages": "1407-1419", "proceedings_title": null, "publisher": "", "title": "Antioxidants & redox signaling", "volume": "34", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "High-Precision Sulfur Metabolomics Innovated by a New Specific Probe for Trapping Reactive Sulfur Species.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "In neuroscience, it is fundamental to understand how sensory stimuli are translated into neural activity at the entry point of sensory systems. In the olfactory system, odorants inhaled into the nasal cavity are detected by ~1,000 types of odorant receptors (ORs) that are expressed by olfactory sensory neurons (OSNs). Since each OSN expresses only one type of odorant receptor, the odor-evoked responses reflect the interaction between odorants and the expressed OR. The responses of OSN somata are often measured by calcium imaging and electrophysiological techniques; however, previous techniques require tissue dissection or cell dissociation, rendering it difficult to investigate physiological responses. Here, we describe a protocol that allows us to observe odor-evoked responses of individual OSN somata in the mouse olfactory epithelium in vivo. Two-photon excitation through the thinned skull enables highly-sensitive calcium imaging using a genetically encoded calcium indicator, GCaMP. Recording of odor-evoked responses in OSN somata in freely breathing mice will be fundamental to understanding how odor information is processed at the periphery and higher circuits in the brain.", "classifications": [ { "id": "Imai", "label": "Group Imai", "parent": "Enomoto", "type": "group" }, { "id": "Enomoto", "label": "Team Enomoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Shigenori", "last_name": "Inagaki", "name": null }, { "creator_type": "author", "first_name": "Ryo", "last_name": "Iwata", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Imai", "name": null } ], "identifiers": { "doi": { "normalized": "10.21769/bioprotoc.4055" }, "pmcid": { "normalized": "PMC8260259" }, "pmid": { "normalized": "34262998" } }, "mesh": [], "publication": { "conference_name": null, "date": "2021 Jun 20", "date_precision": "day", "issue": "12", "normalized_date": "2021-06-20", "pages": "e4055", "proceedings_title": null, "publisher": "", "title": "Bio-protocol", "volume": "11", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "In vivo Optical Access to Olfactory Sensory Neuronsin the Mouse Olfactory Epithelium.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Interactive networks of transcription factors (TFs) have critical roles in epigenetic and gene regulation for cancer progression. It is required to clarify underlying mechanisms for transcriptional activation through concerted efforts of TFs. Here, we show the essential role of disease phase-specific TF collaboration changes in advanced prostate cancer (PC). Investigation of the transcriptome in castration-resistant PC (CRPC) revealed OCT4 as a key TF in the disease pathology. OCT4 confers epigenetic changes by promoting complex formation with FOXA1 and androgen receptor (AR), the central signals for the progression to CRPC. Meanwhile, OCT4 facilitates a distinctive complex formation with nuclear respiratory factor 1 (NRF1) to gain chemo-resistance in the absence of AR. Mechanistically, we reveal that OCT4 increases large droplet formations with AR/FOXA1 as well as NRF1 in vitro. Disruption of TF collaborations using a nucleoside analogue, ribavirin, inhibited treatment-resistant PC tumor growth. Thus, our findings highlight the formation of TF collaborations as a potent therapeutic target in advanced cancer.", "classifications": [ { "id": "Suzuki", "label": "Group Suzuki", "parent": "Takekawa", "type": "group" }, { "id": "Takekawa", "label": "Team Takekawa", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Ken-Ichi", "last_name": "Takayama", "name": null }, { "creator_type": "author", "first_name": "Takeo", "last_name": "Kosaka", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Hongo", "name": null }, { "creator_type": "author", "first_name": "Mototsugu", "last_name": "Oya", "name": null }, { "creator_type": "author", "first_name": "Tetsuya", "last_name": "Fujimura", "name": null }, { "creator_type": "author", "first_name": "Yutaka", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Inoue", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41467-021-23974-4" }, "pmcid": { "normalized": "PMC8213733" }, "pmid": { "normalized": "34145268" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Antineoplastic Agents", "descriptor_ui": "D000970", "major_topic": false }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Cell Proliferation", "descriptor_ui": "D049109", "major_topic": false }, { "descriptor": "Disease Models, Animal", "descriptor_ui": "D004195", "major_topic": false }, { "descriptor": "Drug Resistance, Neoplasm", "descriptor_ui": "D019008", "major_topic": false }, { "descriptor": "Gene Expression Regulation", "descriptor_ui": "D005786", "major_topic": false }, { "descriptor": "Gene Expression Regulation, Neoplastic", "descriptor_ui": "D015972", "major_topic": false }, { "descriptor": "HEK293 Cells", "descriptor_ui": "D057809", "major_topic": false }, { "descriptor": "Hepatocyte Nuclear Factor 3-alpha", "descriptor_ui": "D051541", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred BALB C", "descriptor_ui": "D008807", "major_topic": false }, { "descriptor": "Mice, Nude", "descriptor_ui": "D008819", "major_topic": false }, { "descriptor": "Nuclear Respiratory Factor 1", "descriptor_ui": "D051266", "major_topic": false }, { "descriptor": "Octamer Transcription Factor-3", "descriptor_ui": "D050814", "major_topic": false }, { "descriptor": "Prostatic Neoplasms, Castration-Resistant", "descriptor_ui": "D064129", "major_topic": false }, { "descriptor": "Receptors, Androgen", "descriptor_ui": "D011944", "major_topic": false }, { "descriptor": "Ribavirin", "descriptor_ui": "D012254", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Transcriptome", "descriptor_ui": "D059467", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Jun 18", "date_precision": "day", "issue": "1", "normalized_date": "2021-06-18", "pages": "3766", "proceedings_title": null, "publisher": "", "title": "Nature communications", "volume": "12", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Subtype-specific collaborative transcription factor networks are promoted by OCT4 in the progression of prostate cancer.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "A series of cyclic surfactants were synthesized from a poly(ethylene glycol) (PEG) homopolymer and Pluronic surfactants L35, L64, P123, F68, 10R5, and 17R4, and their interfacial activity depending on the topology, chain ends, and block sequence was investigated. The cyclization was performed in a single step through etherification of the PEG homopolymer and the hydrophilic-hydrophobic-hydrophilic (ABA type) poly(ethylene glycol)-poly(propylene glycol)-poly(ethylene glycol) (PEG-PPG-PEG), while the hydrophobic-hydrophilic-hydrophobic (BAB type) PPG-PEG-PPG was cyclized via acetalization. The cyclized surfactants were rigorously characterized by nuclear magnetic resonance spectroscopy and size exclusion chromatography. Cyclization of the surfactants induced a significant decrease in the hydrodynamic volume, which was more pronounced than that of the PEG homopolymer. Surface tension (gamma) measurements indicated that the interfacial activity of the cyclized surfactants is stronger than their corresponding linear precursors, due to the increase in the surfactant density at the air-water interface as a consequence of the decreased molecular occupational area (A) upon cyclization. In the case of the PEG homopolymer, A considerably decreased from 410 A(2) for the linear PEG prepolymer to 100 A(2) for the cyclized PEG product. While the effects of chain-end groups were found to be limited to surfactants of relatively small molecular weights, the influence of cyclization depended strongly on the hydrophilic/hydrophobic ratio; the higher the PEG composition the surfactants had, the larger the decrease in gamma and A; in other words, stronger enhancement in the interfacial activity was observed.", "classifications": [ { "id": "Yamamoto", "label": "Group Yamamoto", "parent": "Toyoshima", "type": "group" }, { "id": "Toyoshima", "label": "Team Toyoshima", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Tomohisa", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Satoru", "last_name": "Chimura", "name": null }, { "creator_type": "author", "first_name": "Yubo", "last_name": "Wang", "name": null }, { "creator_type": "author", "first_name": "Tomoko", "last_name": "Ono", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Isono", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Tajima", "name": null }, { "creator_type": "author", "first_name": "Toshifumi", "last_name": "Satoh", "name": null }, { "creator_type": "author", "first_name": "Shin-Ichiro", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Daichi", "last_name": "Ida", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Yamamoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/acs.langmuir.1c00513" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "34048253" } }, "mesh": [], "publication": { "conference_name": null, "date": "2021 Jun 15", "date_precision": "day", "issue": "23", "normalized_date": "2021-06-15", "pages": "6974-6984", "proceedings_title": null, "publisher": "", "title": "Langmuir : the ACS journal of surfaces and colloids", "volume": "37", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Cyclization of PEG and Pluronic Surfactants and the Effects of the Topology on Their Interfacial Activity.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "We demonstrate a method for label-free monitoring of hydrolytic activity of crystalline-chitin-degrading enzyme, chitinase, by means of Raman spectroscopy. We found that crystalline chitin exhibited a characteristic Raman peak at 2995 cm-1, which did not appear in the reaction product, N,N'-diacetylchitobiose. We used this Raman peak as a marker of crystalline chitin degradation to monitor the hydrolytic activity of chitinase. When the crystalline chitin suspension and chitinase were mixed together, the peak intensity of crystalline chitin at 2995 cm-1 was linearly decreased depending on incubation time. The decrease in peak intensity was inversely correlated with the increase in the amount of released N,N'-diacetylchitobiose, which was measured by conventional colorimetric assay with alkaline ferricyanide. Our result, presented here, provides a new method for simple, in situ, and label-free monitoring of enzymatic activity of chitinase.", "classifications": [ { "id": "Fujita", "label": "Group Fujita", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Jun", "last_name": "Ando", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Kawagoe", "name": null }, { "creator_type": "author", "first_name": "Akihiko", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Ryota", "last_name": "Iino", "name": null }, { "creator_type": "author", "first_name": "Katsumasa", "last_name": "Fujita", "name": null } ], "identifiers": { "doi": { "normalized": "10.1039/d1an00581b" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "34060547" } }, "mesh": [ { "descriptor": "Chitin", "descriptor_ui": "D002686", "major_topic": false }, { "descriptor": "Chitinases", "descriptor_ui": "D002688", "major_topic": true }, { "descriptor": "Hydrolysis", "descriptor_ui": "D006868", "major_topic": false }, { "descriptor": "Spectrum Analysis, Raman", "descriptor_ui": "D013059", "major_topic": false }, { "descriptor": "Suspensions", "descriptor_ui": "D013535", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Jun 14", "date_precision": "day", "issue": "12", "normalized_date": "2021-06-14", "pages": "4087-4094", "proceedings_title": null, "publisher": "", "title": "The Analyst", "volume": "146", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Label-free monitoring of crystalline chitin hydrolysis by chitinase based on Raman spectroscopy.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Patients with chronic kidney disease (CKD) commonly exhibit hypercoagulability. Increased levels of uremic toxins cause thrombogenicity by increasing tissue factor (TF) expression and activating the extrinsic coagulation cascade. TF is induced in monocytes and macrophages under pathological conditions, such as inflammatory diseases. However, the role of monocyte myeloid cell TF in CKD progression remains unclear. We aimed to clarify this issue, and the present study found that patients with CKD had elevated levels of D-dimer, a marker of fibrin degradation, which was associated with decreased estimated glomerular filtration rate and increased serum levels of uremic toxins, such as indoxyl sulfate. In vitro studies showed that several uremic toxins increased cellular TF levels in monocytic THP-1 cells. Mice with TF specifically deleted in myeloid cells were fed an adenine diet to cause uremic kidney injury. Myeloid TF deletion reduced tubular injury and pro-inflammatory gene expression in the kidneys of adenine-induced CKD but did not improve renal function as measured by plasma creatinine or blood urea nitrogen. Collectively, our findings suggest a novel concept of pathogenesis of coagulation-mediated kidney injury, in which elevated TF levels in monocytes under uremic conditions is partly involved in the development of CKD.", "classifications": [ { "id": "Okamoto", "label": "Group Okamoto", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Shu", "last_name": "Yamakage", "name": null }, { "creator_type": "author", "first_name": "Yuji", "last_name": "Oe", "name": null }, { "creator_type": "author", "first_name": "Emiko", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Okamoto", "name": null }, { "creator_type": "author", "first_name": "Akiyo", "last_name": "Sekimoto", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Kumakura", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Mai", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Tasuku", "last_name": "Nagasawa", "name": null }, { "creator_type": "author", "first_name": "Mariko", "last_name": "Miyazaki", "name": null }, { "creator_type": "author", "first_name": "Sadayoshi", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Nigel", "last_name": "Mackman", "name": null }, { "creator_type": "author", "first_name": "Nobuyuki", "last_name": "Takahashi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41598-021-91586-5" }, "pmcid": { "normalized": "PMC8190319" }, "pmid": { "normalized": "34108522" } }, "mesh": [ { "descriptor": "Adenine", "descriptor_ui": "D000225", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Fibrin Fibrinogen Degradation Products", "descriptor_ui": "D005338", "major_topic": false }, { "descriptor": "Glomerular Filtration Rate", "descriptor_ui": "D005919", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Kidney Tubules", "descriptor_ui": "D007684", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Myeloid Cells", "descriptor_ui": "D022423", "major_topic": false }, { "descriptor": "Renal Insufficiency, Chronic", "descriptor_ui": "D051436", "major_topic": false }, { "descriptor": "Thromboplastin", "descriptor_ui": "D013925", "major_topic": false }, { "descriptor": "Toxins, Biological", "descriptor_ui": "D014118", "major_topic": false }, { "descriptor": "Uremia", "descriptor_ui": "D014511", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Jun 9", "date_precision": "day", "issue": "1", "normalized_date": "2021-06-09", "pages": "12159", "proceedings_title": null, "publisher": "", "title": "Scientific reports", "volume": "11", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Myeloid cell-derived coagulation tissue factor is associated with renal tubular damage in mice fed an adenine diet.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Organization of dynamic cellular structure is crucial for a variety of cellular functions. In this study, we report that Drosophila and Aedes have highly elastic cell membranes with extremely low membrane tension and high resistance to mechanical stress. In contrast to other eukaryotic cells, phospholipids are symmetrically distributed between the bilayer leaflets of the insect plasma membrane, where phospholipid scramblase (XKR) that disrupts the lipid asymmetry is constitutively active. We also demonstrate that XKR-facilitated phospholipid scrambling promotes the deformability of cell membranes by regulating both actin cortex dynamics and mechanical properties of the phospholipid bilayer. Moreover, XKR-mediated construction of elastic cell membranes is essential for hemocyte circulation in the Drosophila cardiovascular system. Deformation of mammalian cells is also enhanced by the expression of Aedes XKR, and thus phospholipid scrambling may contribute to formation of highly deformable cell membranes in a variety of living eukaryotic cells.", "classifications": [ { "id": "Shintaku", "label": "Group Shintaku", "parent": "Shintaku", "type": "group" }, { "id": "Shintaku", "label": "Team Shintaku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Akifumi", "last_name": "Shiomi", "name": null }, { "creator_type": "author", "first_name": "Kohjiro", "last_name": "Nagao", "name": null }, { "creator_type": "author", "first_name": "Nobuhiro", "last_name": "Yokota", "name": null }, { "creator_type": "author", "first_name": "Masaki", "last_name": "Tsuchiya", "name": null }, { "creator_type": "author", "first_name": "Utako", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Naoto", "last_name": "Juni", "name": null }, { "creator_type": "author", "first_name": "Yuji", "last_name": "Hara", "name": null }, { "creator_type": "author", "first_name": "Masayuki X.", "last_name": "Mori", "name": null }, { "creator_type": "author", "first_name": "Yasuo", "last_name": "Mori", "name": null }, { "creator_type": "author", "first_name": "Kumiko", "last_name": "Ui-Tei", "name": null }, { "creator_type": "author", "first_name": "Motohide", "last_name": "Murate", "name": null }, { "creator_type": "author", "first_name": "Toshihide", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Yuri", "last_name": "Nishino", "name": null }, { "creator_type": "author", "first_name": "Atsuo", "last_name": "Miyazawa", "name": null }, { "creator_type": "author", "first_name": "Akihisa", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Ryo", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Stefan", "last_name": "Kaufmann", "name": null }, { "creator_type": "author", "first_name": "Motomu", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Kazuya", "last_name": "Tatsumi", "name": null }, { "creator_type": "author", "first_name": "Kazuyoshi", "last_name": "Nakabe", "name": null }, { "creator_type": "author", "first_name": "Hirofumi", "last_name": "Shintaku", "name": null }, { "creator_type": "author", "first_name": "Semen", "last_name": "Yesylevsky", "name": null }, { "creator_type": "author", "first_name": "Mikhail", "last_name": "Bogdanov", "name": null }, { "creator_type": "author", "first_name": "Masato", "last_name": "Umeda", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.celrep.2021.109219" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "34107250" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Membrane", "descriptor_ui": "D002462", "major_topic": false }, { "descriptor": "Drosophila", "descriptor_ui": "D004330", "major_topic": false }, { "descriptor": "Insecta", "descriptor_ui": "D007313", "major_topic": false }, { "descriptor": "Phospholipid Transfer Proteins", "descriptor_ui": "D049294", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Jun 8", "date_precision": "day", "issue": "10", "normalized_date": "2021-06-08", "pages": "109219", "proceedings_title": null, "publisher": "", "title": "Cell reports", "volume": "35", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Extreme deformability of insect cell membranes is governed by phospholipid scrambling.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The human hand can detect both form and texture information of a contact surface. The detection of skin displacement (sustained stimulus) and changes in skin displacement (transient stimulus) are thought to be mediated in different tactile channels; however, tactile form perception may use both types of information. Here, we studied whether both the temporal frequency and the temporal coherency information of tactile stimuli encoded in sensory neurons could be used to recognize the form of contact surfaces. We used the fishbone tactile illusion (FTI), a known tactile phenomenon, as a probe for tactile form perception in humans. This illusion typically occurs with a surface geometry that has a smooth bar and coarse textures in its adjacent areas. When stroking the central bar back and forth with a fingertip, a human observer perceives a hollow surface geometry even though the bar is physically flat. We used a passive high-density pin matrix to extract only the vertical information of the contact surface, suppressing tangential displacement from surface rubbing. Participants in the psychological experiment reported indented surface geometry by tracing over the FTI textures with pin matrices of the different spatial densities (1.0 and 2.0 mm pin intervals). Human participants reported that the relative magnitude of perceived surface indentation steeply decreased when pins in the adjacent areas vibrated in synchrony. To address possible mechanisms for tactile form perception in the FTI, we developed a computational model of sensory neurons to estimate temporal patterns of action potentials from tactile receptive fields. Our computational data suggest that (1) the temporal asynchrony of sensory neuron responses is correlated with the relative magnitude of perceived surface indentation and (2) the spatiotemporal change of displacements in tactile stimuli are correlated with the asynchrony of simulated sensory neuron responses for the fishbone surface patterns. Based on these results, we propose that both the frequency and the asynchrony of temporal activity in sensory neurons could produce tactile form perception.", "classifications": [ { "id": "Nagayama", "label": "Group Nagayama", "parent": "Fujiwara", "type": "group" }, { "id": "Fujiwara", "label": "Team Fujiwara", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Masashi", "last_name": "Nakatani", "name": null }, { "creator_type": "author", "first_name": "Yasuaki", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Kota", "last_name": "Ohno", "name": null }, { "creator_type": "author", "first_name": "Masaaki", "last_name": "Uesaka", "name": null }, { "creator_type": "author", "first_name": "Sayako", "last_name": "Mogami", "name": null }, { "creator_type": "author", "first_name": "Zixia", "last_name": "Zhao", "name": null }, { "creator_type": "author", "first_name": "Takamichi", "last_name": "Sushida", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Kitahata", "name": null }, { "creator_type": "author", "first_name": "Masaharu", "last_name": "Nagayama", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41598-021-90661-1" }, "pmcid": { "normalized": "PMC8175693" }, "pmid": { "normalized": "34083558" } }, "mesh": [ { "descriptor": "Data Analysis", "descriptor_ui": "D000078332", "major_topic": false }, { "descriptor": "Hand", "descriptor_ui": "D006225", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Models, Theoretical", "descriptor_ui": "D008962", "major_topic": false }, { "descriptor": "Physical Stimulation", "descriptor_ui": "D010812", "major_topic": true }, { "descriptor": "Psychophysics", "descriptor_ui": "D011601", "major_topic": false }, { "descriptor": "Touch", "descriptor_ui": "D014110", "major_topic": false }, { "descriptor": "Touch Perception", "descriptor_ui": "D055698", "major_topic": true } ], "publication": { "conference_name": null, "date": "2021 Jun 3", "date_precision": "day", "issue": "1", "normalized_date": "2021-06-03", "pages": "11737", "proceedings_title": null, "publisher": "", "title": "Scientific reports", "volume": "11", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Temporal coherency of mechanical stimuli modulates tactile form perception.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Trophoblasts are extraembryonic cells that are essential for maintaining pregnancy. Human trophoblasts arise from the morula as trophectoderm (TE), which, after implantation, differentiates into cytotrophoblasts (CTs), syncytiotrophoblasts (STs), and extravillous trophoblasts (EVTs), composing the placenta. Here we show that naive, but not primed, human pluripotent stem cells (PSCs) recapitulate trophoblast development. Naive PSC-derived TE and CTs (nCTs) recreated human and monkey TE-to-CT transition. nCTs self-renewed as CT stem cells and had the characteristics of proliferating villous CTs and CTs in the cell column of the first trimester. Notably, although primed PSCs differentiated into trophoblast-like cells (BMP4, A83-01, and PD173074 [BAP]-treated primed PSCs [pBAPs]), pBAPs were distinct from nCTs and human placenta-derived CT stem cells, exhibiting properties consistent with the amnion. Our findings establish an authentic paradigm for human trophoblast development, demonstrating the invaluable properties of naive human PSCs. Our system provides a platform to study the molecular mechanisms underlying trophoblast development and related diseases.", "classifications": [ { "id": "Yamamoto", "label": "Group Yamamoto", "parent": "Toyoshima", "type": "group" }, { "id": "Toyoshima", "label": "Team Toyoshima", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Shingo", "last_name": "Io", "name": null }, { "creator_type": "author", "first_name": "Mio", "last_name": "Kabata", "name": null }, { "creator_type": "author", "first_name": "Yoshiki", "last_name": "Iemura", "name": null }, { "creator_type": "author", "first_name": "Katsunori", "last_name": "Semi", "name": null }, { "creator_type": "author", "first_name": "Nobuhiro", "last_name": "Morone", "name": null }, { "creator_type": "author", "first_name": "Atsutaka", "last_name": "Minagawa", "name": null }, { "creator_type": "author", "first_name": "Bo", "last_name": "Wang", "name": null }, { "creator_type": "author", "first_name": "Ikuhiro", "last_name": "Okamoto", "name": null }, { "creator_type": "author", "first_name": "Tomonori", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Yoji", "last_name": "Kojima", "name": null }, { "creator_type": "author", "first_name": "Chizuru", "last_name": "Iwatani", "name": null }, { "creator_type": "author", "first_name": "Hideaki", "last_name": "Tsuchiya", "name": null }, { "creator_type": "author", "first_name": "Belinda", "last_name": "Kaswandy", "name": null }, { "creator_type": "author", "first_name": "Eiji", "last_name": "Kondoh", "name": null }, { "creator_type": "author", "first_name": "Shin", "last_name": "Kaneko", "name": null }, { "creator_type": "author", "first_name": "Knut", "last_name": "Woltjen", "name": null }, { "creator_type": "author", "first_name": "Mitinori", "last_name": "Saitou", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Masaki", "last_name": "Mandai", "name": null }, { "creator_type": "author", "first_name": "Yasuhiro", "last_name": "Takashima", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.stem.2021.03.013" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "33831365" } }, "mesh": [ { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Placenta", "descriptor_ui": "D010920", "major_topic": false }, { "descriptor": "Pluripotent Stem Cells", "descriptor_ui": "D039904", "major_topic": true }, { "descriptor": "Pregnancy", "descriptor_ui": "D011247", "major_topic": false }, { "descriptor": "Trophoblasts", "descriptor_ui": "D014327", "major_topic": true } ], "publication": { "conference_name": null, "date": "2021 Jun 3", "date_precision": "day", "issue": "6", "normalized_date": "2021-06-03", "pages": "1023-1039.e13", "proceedings_title": null, "publisher": "", "title": "Cell stem cell", "volume": "28", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Capturing human trophoblast development with naive pluripotent stem cells in vitro.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Triplet carbenes (TCs) are of great interest due to their magnetic properties and reactivity, which descend from TCs' unique electronic state. However, the reactivity and stability of TCs are usually a trade-off, and it is difficult to achieve both at the same time. In this work, we were able to enhance the thermal stability of a TC species while maintaining its reactivity by confining them in the nanospace of a metal-organic framework (MOF). We synthesized a new MOF using a TC precursor; subsequently, TCs were generated by photostimulation. The TCs generated in the MOF nanospace were detectable up to 170 K, whereas their non-MOF-confined counterparts (bare ligand) could not be detected above 100 K. In addition, the reactivity of TC generated in MOF with O(2) was drastically improved compared to that of bare ligand. Our approach is generally applicable to the stabilization of highly reactive species, whose reactivity needs to be preserved.", "classifications": [ { "id": "Hijikata", "label": "Group Hijikata", "parent": "Tsuchiya", "type": "group" }, { "id": "Tsuchiya", "label": "Team Tsuchiya", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Toshinobu", "last_name": "Nakajo", "name": null }, { "creator_type": "author", "first_name": "Jun", "last_name": "Kumagai", "name": null }, { "creator_type": "author", "first_name": "Shinpei", "last_name": "Kusaka", "name": null }, { "creator_type": "author", "first_name": "Akihiro", "last_name": "Hori", "name": null }, { "creator_type": "author", "first_name": "Yuh", "last_name": "Hijikata", "name": null }, { "creator_type": "author", "first_name": "Jenny", "last_name": "Pirillo", "name": null }, { "creator_type": "author", "first_name": "Yunsheng", "last_name": "Ma", "name": null }, { "creator_type": "author", "first_name": "Ryotaro", "last_name": "Matsuda", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/jacs.1c02430" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "34011147" } }, "mesh": [], "publication": { "conference_name": null, "date": "2021 Jun 2", "date_precision": "day", "issue": "21", "normalized_date": "2021-06-02", "pages": "8129-8136", "proceedings_title": null, "publisher": "", "title": "Journal of the American Chemical Society", "volume": "143", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Triplet Carbene with Highly Enhanced Thermal Stability in the Nanospace of a Metal-Organic Framework.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Maternal mammals exhibit heightened motivation to care for offspring, but the underlying neuromolecular mechanisms have yet to be clarified. Here, we report that the calcitonin receptor (Calcr) and its ligand amylin are expressed in distinct neuronal populations in the medial preoptic area (MPOA) and are upregulated in mothers. Calcr+ MPOA neurons activated by parental care project to somatomotor and monoaminergic brainstem nuclei. Retrograde monosynaptic tracing reveals that significant modification of afferents to Calcr+ neurons occurs in mothers. Knockdown of either Calcr or amylin gene expression hampers risk-taking maternal care, and specific silencing of Calcr+ MPOA neurons inhibits nurturing behaviors, while pharmacogenetic activation prevents infanticide in virgin males. These data indicate that Calcr+ MPOA neurons are required for both maternal and allomaternal nurturing behaviors and that upregulation of amylin-Calcr signaling in the MPOA at least partially mediates risk-taking maternal care, possibly via modified connectomics of Calcr+ neurons postpartum.", "classifications": [ { "id": "Miyamichi", "label": "Group Miyamichi", "parent": "Enomoto", "type": "group" }, { "id": "Enomoto", "label": "Team Enomoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Chihiro", "last_name": "Yoshihara", "name": null }, { "creator_type": "author", "first_name": "Kenichi", "last_name": "Tokita", "name": null }, { "creator_type": "author", "first_name": "Teppo", "last_name": "Maruyama", "name": null }, { "creator_type": "author", "first_name": "Misato", "last_name": "Kaneko", "name": null }, { "creator_type": "author", "first_name": "Yousuke", "last_name": "Tsuneoka", "name": null }, { "creator_type": "author", "first_name": "Kansai", "last_name": "Fukumitsu", "name": null }, { "creator_type": "author", "first_name": "Eri", "last_name": "Miyazawa", "name": null }, { "creator_type": "author", "first_name": "Kazutaka", "last_name": "Shinozuka", "name": null }, { "creator_type": "author", "first_name": "Arthur J.", "last_name": "Huang", "name": null }, { "creator_type": "author", "first_name": "Katsuhiko", "last_name": "Nishimori", "name": null }, { "creator_type": "author", "first_name": "Thomas J.", "last_name": "McHugh", "name": null }, { "creator_type": "author", "first_name": "Minoru", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Shigeyoshi", "last_name": "Itohara", "name": null }, { "creator_type": "author", "first_name": "Kazushige", "last_name": "Touhara", "name": null }, { "creator_type": "author", "first_name": "Kazunari", "last_name": "Miyamichi", "name": null }, { "creator_type": "author", "first_name": "Kumi O.", "last_name": "Kuroda", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.celrep.2021.109204" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "34077719" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Behavior, Animal", "descriptor_ui": "D001522", "major_topic": false }, { "descriptor": "Estrogens", "descriptor_ui": "D004967", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Gene Silencing", "descriptor_ui": "D020868", "major_topic": false }, { "descriptor": "Gene Targeting", "descriptor_ui": "D018390", "major_topic": false }, { "descriptor": "Islet Amyloid Polypeptide", "descriptor_ui": "D058228", "major_topic": false }, { "descriptor": "Lactation", "descriptor_ui": "D007774", "major_topic": false }, { "descriptor": "Ligands", "descriptor_ui": "D008024", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Maternal Behavior", "descriptor_ui": "D008425", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Postpartum Period", "descriptor_ui": "D049590", "major_topic": false }, { "descriptor": "Preoptic Area", "descriptor_ui": "D011301", "major_topic": false }, { "descriptor": "Prolactin", "descriptor_ui": "D011388", "major_topic": false }, { "descriptor": "Receptors, Calcitonin", "descriptor_ui": "D018003", "major_topic": false }, { "descriptor": "Risk-Taking", "descriptor_ui": "D012309", "major_topic": true }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": true }, { "descriptor": "Synapses", "descriptor_ui": "D013569", "major_topic": false }, { "descriptor": "Up-Regulation", "descriptor_ui": "D015854", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Jun 1", "date_precision": "day", "issue": "9", "normalized_date": "2021-06-01", "pages": "109204", "proceedings_title": null, "publisher": "", "title": "Cell reports", "volume": "35", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Calcitonin receptor signaling in the medial preoptic area enables risk-taking maternal care.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The mammalian brain is highly vulnerable to oxygen deprivation, yet the mechanism underlying the brain's sensitivity to hypoxia is incompletely understood. Hypoxia induces accumulation of hydrogen sulfide, a gas that inhibits mitochondrial respiration. Here, we show that, in mice, rats, and naturally hypoxia-tolerant ground squirrels, the sensitivity of the brain to hypoxia is inversely related to the levels of sulfide:quinone oxidoreductase (SQOR) and the capacity to catabolize sulfide. Silencing SQOR increased the sensitivity of the brain to hypoxia, whereas neuron-specific SQOR expression prevented hypoxia-induced sulfide accumulation, bioenergetic failure, and ischemic brain injury. Excluding SQOR from mitochondria increased sensitivity to hypoxia not only in the brain but also in heart and liver. Pharmacological scavenging of sulfide maintained mitochondrial respiration in hypoxic neurons and made mice resistant to hypoxia. These results illuminate the critical role of sulfide catabolism in energy homeostasis during hypoxia and identify a therapeutic target for ischemic brain injury.", "classifications": [ { "id": "JPMJCR2024", "label": "JPMJCR2024", "researcher": "Motohiro Nishida", "type": "grant" }, { "id": "Akaike", "label": "Group Akaike", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Group Nishida", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Eizo", "last_name": "Marutani", "name": null }, { "creator_type": "author", "first_name": "Masanobu", "last_name": "Morita", "name": null }, { "creator_type": "author", "first_name": "Shuichi", "last_name": "Hirai", "name": null }, { "creator_type": "author", "first_name": "Shinichi", "last_name": "Kai", "name": null }, { "creator_type": "author", "first_name": "Robert M. H.", "last_name": "Grange", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Miyazaki", "name": null }, { "creator_type": "author", "first_name": "Fumiaki", "last_name": "Nagashima", "name": null }, { "creator_type": "author", "first_name": "Lisa", "last_name": "Traeger", "name": null }, { "creator_type": "author", "first_name": "Aurora", "last_name": "Magliocca", "name": null }, { "creator_type": "author", "first_name": "Tomoaki", "last_name": "Ida", "name": null }, { "creator_type": "author", "first_name": "Tetsuro", "last_name": "Matsunaga", "name": null }, { "creator_type": "author", "first_name": "Daniel R.", "last_name": "Flicker", "name": null }, { "creator_type": "author", "first_name": "Benjamin", "last_name": "Corman", "name": null }, { "creator_type": "author", "first_name": "Naohiro", "last_name": "Mori", "name": null }, { "creator_type": "author", "first_name": "Yumiko", "last_name": "Yamazaki", "name": null }, { "creator_type": "author", "first_name": "Annabelle", "last_name": "Batten", "name": null }, { "creator_type": "author", "first_name": "Rebecca", "last_name": "Li", "name": null }, { "creator_type": "author", "first_name": "Tomohiro", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Takamitsu", "last_name": "Ikeda", "name": null }, { "creator_type": "author", "first_name": "Akito", "last_name": "Nakagawa", "name": null }, { "creator_type": "author", "first_name": "Dmitriy N.", "last_name": "Atochin", "name": null }, { "creator_type": "author", "first_name": "Hideshi", "last_name": "Ihara", "name": null }, { "creator_type": "author", "first_name": "Benjamin A.", "last_name": "Olenchock", "name": null }, { "creator_type": "author", "first_name": "Xinggui", "last_name": "Shen", "name": null }, { "creator_type": "author", "first_name": "Motohiro", "last_name": "Nishida", "name": null }, { "creator_type": "author", "first_name": "Kenjiro", "last_name": "Hanaoka", "name": null }, { "creator_type": "author", "first_name": "Christopher G.", "last_name": "Kevil", "name": null }, { "creator_type": "author", "first_name": "Ming", "last_name": "Xian", "name": null }, { "creator_type": "author", "first_name": "Donald B.", "last_name": "Bloch", "name": null }, { "creator_type": "author", "first_name": "Takaaki", "last_name": "Akaike", "name": null }, { "creator_type": "author", "first_name": "Allyson G.", "last_name": "Hindle", "name": null }, { "creator_type": "author", "first_name": "Hozumi", "last_name": "Motohashi", "name": null }, { "creator_type": "author", "first_name": "Fumito", "last_name": "Ichinose", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41467-021-23363-x" }, "pmcid": { "normalized": "PMC8149856" }, "pmid": { "normalized": "34035265" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Brain", "descriptor_ui": "D001921", "major_topic": false }, { "descriptor": "Brain Injuries", "descriptor_ui": "D001930", "major_topic": false }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Hydrogen Sulfide", "descriptor_ui": "D006862", "major_topic": false }, { "descriptor": "Hypoxia", "descriptor_ui": "D000860", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Membrane Potential, Mitochondrial", "descriptor_ui": "D053078", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Inbred DBA", "descriptor_ui": "D008811", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Mitochondria", "descriptor_ui": "D008928", "major_topic": false }, { "descriptor": "NAD", "descriptor_ui": "D009243", "major_topic": false }, { "descriptor": "Quinone Reductases", "descriptor_ui": "D011808", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Rats, Sprague-Dawley", "descriptor_ui": "D017207", "major_topic": false }, { "descriptor": "RNA Interference", "descriptor_ui": "D034622", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 May 25", "date_precision": "day", "issue": "1", "normalized_date": "2021-05-25", "pages": "3108", "proceedings_title": null, "publisher": "", "title": "Nature communications", "volume": "12", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Sulfide catabolism ameliorates hypoxic brain injury.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "We improved the three-dimensional spatial resolution of laser scanning transmission microscopy by exploiting the saturated absorption of dye molecules. The saturated absorption is induced by the high-intensity light irradiation and localises the signal within the centre of the focal spot. Our numerical calculation indicates that the spatial resolution in transmission imaging is significantly improved for both lateral and axial directions using nonlinear transmitted signals induced by saturated absorption. We experimentally demonstrated the improvement of the three-dimensional resolution by observing fine structures of stained rat kidney tissues, which were not able to be visualised by conventional laser scanning transmission microscopy.", "classifications": [ { "id": "Fujita", "label": "Group Fujita", "parent": "Fujita", "type": "group" }, { "id": "Tanaka", "label": "Group Tanaka", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Kentaro", "last_name": "Nishida", "name": null }, { "creator_type": "author", "first_name": "Hikaru", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Ryosuke", "last_name": "Oketani", "name": null }, { "creator_type": "author", "first_name": "Kentaro", "last_name": "Mochizuki", "name": null }, { "creator_type": "author", "first_name": "Kenta", "last_name": "Temma", "name": null }, { "creator_type": "author", "first_name": "Yasuaki", "last_name": "Kumamoto", "name": null }, { "creator_type": "author", "first_name": "Hideo", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Katsumasa", "last_name": "Fujita", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/jmi.13033" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "34028848" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Chemical Phenomena", "descriptor_ui": "D055598", "major_topic": false }, { "descriptor": "Lasers", "descriptor_ui": "D007834", "major_topic": true }, { "descriptor": "Microscopy, Confocal", "descriptor_ui": "D018613", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 May 24", "date_precision": "day", "issue": "", "normalized_date": "2021-05-24", "pages": "", "proceedings_title": null, "publisher": "", "title": "Journal of microscopy", "volume": "", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Using saturated absorption for superresolution laser scanning transmission microscopy.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Genetic differences are a primary reason for differences in the susceptibility and severity of COVID-19. As induced pluripotent stem (iPS) cells maintain the genetic information of the donor, they can be used to model individual differences in SARS-CoV-2 infection in vitro. We found that human iPS cells expressing the SARS-CoV-2 receptor angiotensin-converting enzyme 2 (ACE2) (ACE2-iPS cells) can be infected w SARS-CoV-2. In infected ACE2-iPS cells, the expression of SARS-CoV-2 nucleocapsid protein, budding of viral particles, and production of progeny virus, double membrane spherules, and double-membrane vesicles were confirmed. We performed SARS-CoV-2 infection experiments on ACE2-iPS/ embryonic stem (ES) cells from eight individuals. Male iPS/ES cells were more capable of producing the virus compared with female iPS/ES cells. These findings suggest that ACE2-iPS cells can not only reproduce individual differences in SARS-CoV-2 infection in vitro but also are a useful resource to clarify the causes of individual differences in COVID-19 due to genetic differences.", "classifications": [ { "id": "Yamamoto", "label": "Group Yamamoto", "parent": "Toyoshima", "type": "group" }, { "id": "Toyoshima", "label": "Team Toyoshima", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Emi", "last_name": "Sano", "name": null }, { "creator_type": "author", "first_name": "Sayaka", "last_name": "Deguchi", "name": null }, { "creator_type": "author", "first_name": "Ayaka", "last_name": "Sakamoto", "name": null }, { "creator_type": "author", "first_name": "Natsumi", "last_name": "Mimura", "name": null }, { "creator_type": "author", "first_name": "Ai", "last_name": "Hirabayashi", "name": null }, { "creator_type": "author", "first_name": "Yukiko", "last_name": "Muramoto", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Noda", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Kazuo", "last_name": "Takayama", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.isci.2021.102428" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "33880436" } }, "mesh": [], "publication": { "conference_name": null, "date": "2021 May 21", "date_precision": "day", "issue": "5", "normalized_date": "2021-05-21", "pages": "", "proceedings_title": null, "publisher": "", "title": "iScience", "volume": "24", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Modeling SARS-CoV-2 infection and its individual differences with ACE2-expressing human iPS cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "A reaction-diffusion system with mass conservation modeling cell polarity is considered. A range of the parameters is found where the omega-limit set of the solution is spatially homogeneous, containing constant stationary solution as well as possible nontrivial spatially homogeneous orbit.", "classifications": [ { "id": "Suzuki", "label": "Group Suzuki", "parent": "Takekawa", "type": "group" }, { "id": "Takekawa", "label": "Team Takekawa", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Evangelos", "last_name": "Latos", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Suzuki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/mma.7162" }, "pmcid": { "normalized": "PMC8048841" }, "pmid": { "normalized": "33888921" } }, "mesh": [], "publication": { "conference_name": null, "date": "2021 May 15", "date_precision": "day", "issue": "7", "normalized_date": "2021-05-15", "pages": "5974-5988", "proceedings_title": null, "publisher": "", "title": "Mathematical methods in the applied sciences", "volume": "44", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Mass conservative reaction-diffusion systems describing cell polarity.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Antibody detection is crucial for monitoring host immune responses to specific pathogen antigens (Ags) and evaluating vaccine efficacies. The luciferase immunoprecipitation system (LIPS) was developed for sensitive detection of Ag-specific antibodies in sera from various species. In this study, we describe NanoLIPS, an improved LIPS assay based on NanoLuciferase (NLuc), and employ the assay for monitoring antibody responses following influenza virus infection or vaccination. We generated recombinant influenza virus hemagglutinin (HA) proteins tagged with N-terminal (N-NLuc-HA) or C-terminal (C-NLuc-HA) NLuc reporters. NLuc-HA yielded an at least 20-fold higher signal-to-noise ratio than did a LIPS assay employing a recombinant HA-Gaussia princeps luciferase (GLuc) fusion protein. NanoLIPS-based detection of anti-HA antibodies yielded highly reproducible results with a broad dynamic range. The levels of antibodies against C-NLuc-HA generated by mice vaccinated with recombinant vaccinia virus DIs strain expressing an influenza virus HA protein (rDIs-HA) was significantly correlated with the protective effect elicited by the rDIs-HA vaccine. C-NLuc-HA underwent glycosylation with native conformations and assembly to form a trimeric structure and was detected by monoclonal antibodies that detect conformational epitopes present on the globular head or stalk domain of HA. Therefore, NanoLIPS is applicable for evaluating vaccine efficacy. We also showed that C-NLuc-HA is applicable for detection of HA-specific antibodies in sera from various experimental species, including mouse, cynomolgus macaque, and tree shrew. Thus, NanoLIPS-based detection of HA offers a simple and high-sensitivity method that detects native conformational epitopes and can be used in various experimental animal models.IMPORTANCE Influenza virus HA-specific antibodies can be detected via the hemagglutination inhibition (HI) assay, the neutralization (NT) assay, and the enzyme-linked immunosorbent assay (ELISA). However, these assays have some drawbacks, including narrow dynamic range and the requirement for large amounts of sera. As an alternative to an ELISA-based method, luciferase immunoprecipitation system (LIPS) was developed. We focused on NanoLuciferase (NLuc), which has a small size, higher intensity, and longer stability. In this study, we developed a technically feasible and highly sensitive method for detecting influenza virus-specific antibodies using a NLuc-tagged recombinant HA protein produced in mammalian cells. HA with a C-terminal NLuc extension (C-NLuc-HA) was glycosylated and formed trimeric complexes when expressed in mammalian cells. Furthermore, C-NLuc-HA was recognized not only by monoclonal antibodies that bind to the globular head domain but also by those that bind to the stalk domain. We also demonstrated that the data obtained by this assay correlate with the protection of an experimental vaccine in animal models.", "classifications": [ { "id": "Yamamoto", "label": "Group Yamamoto", "parent": "Toyoshima", "type": "group" }, { "id": "Toyoshima", "label": "Team Toyoshima", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Tomoko", "last_name": "Honda", "name": null }, { "creator_type": "author", "first_name": "Sumiko", "last_name": "Gomi", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Yamane", "name": null }, { "creator_type": "author", "first_name": "Fumihiko", "last_name": "Yasui", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Tsubasa", "last_name": "Munakata", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Itoh", "name": null }, { "creator_type": "author", "first_name": "Kazumasa", "last_name": "Ogasawara", "name": null }, { "creator_type": "author", "first_name": "Takahiro", "last_name": "Sanada", "name": null }, { "creator_type": "author", "first_name": "Kenzaburo", "last_name": "Yamaji", "name": null }, { "creator_type": "author", "first_name": "Yasuhiro", "last_name": "Yasutomi", "name": null }, { "creator_type": "author", "first_name": "Kyoko", "last_name": "Tsukiyama-Kohara", "name": null }, { "creator_type": "author", "first_name": "Michinori", "last_name": "Kohara", "name": null } ], "identifiers": { "doi": { "normalized": "10.1128/msphere.01342-20" }, "pmcid": { "normalized": "PMC8125058" }, "pmid": { "normalized": "33980684" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Antibodies, Monoclonal", "descriptor_ui": "D000911", "major_topic": false }, { "descriptor": "Antibodies, Neutralizing", "descriptor_ui": "D057134", "major_topic": false }, { "descriptor": "Antibodies, Viral", "descriptor_ui": "D000914", "major_topic": false }, { "descriptor": "Epitopes", "descriptor_ui": "D000939", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Hemagglutination Inhibition Tests", "descriptor_ui": "D006385", "major_topic": false }, { "descriptor": "Hemagglutinin Glycoproteins, Influenza Virus", "descriptor_ui": "D019267", "major_topic": false }, { "descriptor": "Immunoprecipitation", "descriptor_ui": "D047468", "major_topic": false }, { "descriptor": "Influenza Vaccines", "descriptor_ui": "D007252", "major_topic": false }, { "descriptor": "Luciferases", "descriptor_ui": "D008156", "major_topic": false }, { "descriptor": "Macaca fascicularis", "descriptor_ui": "D008252", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred BALB C", "descriptor_ui": "D008807", "major_topic": false }, { "descriptor": "Orthomyxoviridae Infections", "descriptor_ui": "D009976", "major_topic": false }, { "descriptor": "Sensitivity and Specificity", "descriptor_ui": "D012680", "major_topic": false }, { "descriptor": "Tupaiidae", "descriptor_ui": "D014418", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 May 12", "date_precision": "day", "issue": "3", "normalized_date": "2021-05-12", "pages": "", "proceedings_title": null, "publisher": "", "title": "mSphere", "volume": "6", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Development and Characterization of a Highly Sensitive NanoLuciferase-Based Immunoprecipitation System for the Detection of Anti-Influenza Virus HA Antibodies.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Live cell imaging using fluorescent DNA markers are an indispensable molecular tool in various biological and biomedical fields. It is a challenge to develop DNA probes that avoid UV light photo-excitation, have high specificity for DNA, are cell-permeable and are compatible with cutting-edge imaging techniques such as super-resolution microscopy. Herein, we present N-aryl pyrido cyanine (N-aryl-PC) derivatives as a class of long absorption DNA markers with absorption in the wide range of visible light. The high DNA specificity and membrane permeability allow the staining of both organelle DNA as well as nuclear DNA, in various cell types, including plant tissues, without the need for washing post-staining. N-aryl-PC dyes are also highly compatible with a separation of photon by lifetime tuning method in stimulated emission depletion microscopy (SPLIT-STED) for super-resolution imaging as well as two-photon microscopy for deep tissue imaging, making it a powerful tool in the life sciences.", "classifications": [ { "id": "JPMJCR1924", "label": "JPMJCR1924", "researcher": "Yuichiro Tsuchiya", "type": "grant" }, { "id": "Sato", "label": "Group Sato", "parent": "Tsuchiya", "type": "group" }, { "id": "Tsuchiya", "label": "Group Tsuchiya", "parent": "Tsuchiya", "type": "group" }, { "id": "Tsuchiya", "label": "Team Tsuchiya", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Kakishi", "last_name": "Uno", "name": null }, { "creator_type": "author", "first_name": "Nagisa", "last_name": "Sugimoto", "name": null }, { "creator_type": "author", "first_name": "Yoshikatsu", "last_name": "Sato", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41467-021-23019-w" }, "pmcid": { "normalized": "PMC8113587" }, "pmid": { "normalized": "33976192" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Arabidopsis", "descriptor_ui": "D017360", "major_topic": false }, { "descriptor": "Benzimidazoles", "descriptor_ui": "D001562", "major_topic": false }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Cell Nucleus", "descriptor_ui": "D002467", "major_topic": false }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "DNA", "descriptor_ui": "D004247", "major_topic": false }, { "descriptor": "Fluorescence", "descriptor_ui": "D005453", "major_topic": false }, { "descriptor": "Fluorescent Dyes", "descriptor_ui": "D005456", "major_topic": false }, { "descriptor": "HeLa Cells", "descriptor_ui": "D006367", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Microscopy, Confocal", "descriptor_ui": "D018613", "major_topic": false }, { "descriptor": "Microscopy, Fluorescence, Multiphoton", "descriptor_ui": "D036641", "major_topic": false }, { "descriptor": "Molecular Structure", "descriptor_ui": "D015394", "major_topic": false }, { "descriptor": "NIH 3T3 Cells", "descriptor_ui": "D041681", "major_topic": false }, { "descriptor": "Organelles", "descriptor_ui": "D015388", "major_topic": false }, { "descriptor": "Staining and Labeling", "descriptor_ui": "D013194", "major_topic": false }, { "descriptor": "Time-Lapse Imaging", "descriptor_ui": "D059008", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 May 11", "date_precision": "day", "issue": "1", "normalized_date": "2021-05-11", "pages": "2650", "proceedings_title": null, "publisher": "", "title": "Nature communications", "volume": "12", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "N-aryl pyrido cyanine derivatives are nuclear and organelle DNA markers for two-photon and super-resolution imaging.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Inter-tissue interaction is fundamental to multicellularity. Although the basement membrane (BM) is located at tissue interfaces, its mode of action in inter-tissue interactions remains poorly understood, mainly because the molecular and structural details of the BM at distinct inter-tissue interfaces remain unclear. By combining quantitative transcriptomics and immunohistochemistry, we systematically identify the cellular origin, molecular identity and tissue distribution of extracellular matrix molecules in mouse hair follicles, and reveal that BM composition and architecture are exquisitely specialized for distinct inter-tissue interactions, including epithelial-fibroblast, epithelial-muscle and epithelial-nerve interactions. The epithelial-fibroblast interface, namely, hair germ-dermal papilla interface, makes asymmetrically organized side-specific heterogeneity in the BM, defined by the newly characterized interface, hook and mesh BMs. One component of these BMs, laminin alpha5, is required for hair cycle regulation and hair germ-dermal papilla anchoring. Our study highlights the significance of BM heterogeneity in distinct inter-tissue interactions.", "classifications": [ { "id": "JPMJCR1926", "label": "JPMJCR1926", "researcher": "Hironobu Fujiwara", "type": "grant" }, { "id": "Fujiwara", "label": "Group Fujiwara", "parent": "Fujiwara", "type": "group" }, { "id": "Fujiwara", "label": "Team Fujiwara", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Ko", "last_name": "Tsutsui", "name": null }, { "creator_type": "author", "first_name": "Hiroki", "last_name": "Machida", "name": null }, { "creator_type": "author", "first_name": "Asako", "last_name": "Nakagawa", "name": null }, { "creator_type": "author", "first_name": "Kyungmin", "last_name": "Ahn", "name": null }, { "creator_type": "author", "first_name": "Ritsuko", "last_name": "Morita", "name": null }, { "creator_type": "author", "first_name": "Kiyotoshi", "last_name": "Sekiguchi", "name": null }, { "creator_type": "author", "first_name": "Jeffrey H.", "last_name": "Miner", "name": null }, { "creator_type": "author", "first_name": "Hironobu", "last_name": "Fujiwara", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41467-021-22881-y" }, "pmcid": { "normalized": "PMC8110968" }, "pmid": { "normalized": "33972551" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Basement Membrane", "descriptor_ui": "D001485", "major_topic": false }, { "descriptor": "Epithelial Cells", "descriptor_ui": "D004847", "major_topic": false }, { "descriptor": "Extracellular Matrix", "descriptor_ui": "D005109", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Fibroblasts", "descriptor_ui": "D005347", "major_topic": false }, { "descriptor": "Hair Follicle", "descriptor_ui": "D018859", "major_topic": false }, { "descriptor": "Immunohistochemistry", "descriptor_ui": "D007150", "major_topic": false }, { "descriptor": "Laminin", "descriptor_ui": "D007797", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Microscopy, Electron, Transmission", "descriptor_ui": "D046529", "major_topic": false }, { "descriptor": "Multigene Family", "descriptor_ui": "D005810", "major_topic": false }, { "descriptor": "Muscle Cells", "descriptor_ui": "D032342", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Single-Cell Analysis", "descriptor_ui": "D059010", "major_topic": false }, { "descriptor": "Transcriptome", "descriptor_ui": "D059467", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 May 10", "date_precision": "day", "issue": "1", "normalized_date": "2021-05-10", "pages": "2577", "proceedings_title": null, "publisher": "", "title": "Nature communications", "volume": "12", "year": 2021 }, "ssbd": { "database": [ "ssbd-database-000170" ], "repository": [ "ssbd-repos-000170" ] }, "title": "Mapping the molecular and structural specialization of the skin basement membrane for inter-tissue interactions.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "We present a systematic study on the support effect of metal-organic frameworks (MOFs), regarding substrate adsorption. A remarkable enhancement of both catalytic activity and selectivity for the ethanol (EtOH) production reaction through acetic acid (AcOH) hydrogenation (AH) was observed on Pt nanoparticles supported on MOFs. The systematic study on catalysis using homogeneously loaded Pt catalysts, in direct contact with seven different MOF supports (MIL-125-NH(2), UiO-66-NH(2), HKUST-1, MIL-101, Zn-MOF-74, Mg-MOF-74, and MIL-121) (abbreviated as Pt/MOFs), found that MOFs having a high affinity for the AcOH substrate (UiO-66-NH(2) and MIL-125-NH(2)) showed high catalytic activity for AH. This is the first demonstration indicating that the adsorption ability of MOFs directly accelerates catalytic performance using the direct contact between the metal and the MOF. In addition, Pt/MIL-125-NH(2) showed a remarkably high EtOH yield (31% at 200 degrees C) in a fixed-bed flow reactor, which was higher by a factor of more than 8 over that observed for Pt/TiO(2), which was the best Pt-based catalyst for this reaction. Infrared spectroscopy and a theoretical study suggested that the MIL-125-NH(2) support plays an important role in high EtOH selectivity by suppressing the formation of the byproduct, ethyl acetate (AcOEt), due to its relatively weak adsorption behavior for EtOH rather than AcOH.", "classifications": [ { "id": "Hijikata", "label": "Group Hijikata", "parent": "Tsuchiya", "type": "group" }, { "id": "Tsuchiya", "label": "Team Tsuchiya", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Shotaro", "last_name": "Yoshimaru", "name": null }, { "creator_type": "author", "first_name": "Masaaki", "last_name": "Sadakiyo", "name": null }, { "creator_type": "author", "first_name": "Nobutaka", "last_name": "Maeda", "name": null }, { "creator_type": "author", "first_name": "Miho", "last_name": "Yamauchi", "name": null }, { "creator_type": "author", "first_name": "Kenichi", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Jenny", "last_name": "Pirillo", "name": null }, { "creator_type": "author", "first_name": "Yuh", "last_name": "Hijikata", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/acsami.1c01100" }, "pmcid": { "normalized": "PMC8288914" }, "pmid": { "normalized": "33877813" } }, "mesh": [], "publication": { "conference_name": null, "date": "2021 May 5", "date_precision": "day", "issue": "17", "normalized_date": "2021-05-05", "pages": "19992-20001", "proceedings_title": null, "publisher": "", "title": "ACS applied materials & interfaces", "volume": "13", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Support Effect of Metal-Organic Frameworks on Ethanol Production through Acetic Acid Hydrogenation.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "In the early fetal stage, the gonads are bipotent and only later become the ovary or testis, depending on the genetic sex. Despite many studies examining how sex determination occurs from biopotential gonads, the spatial and temporal organization of bipotential gonads and their progenitors is poorly understood. Here, using lineage tracing in mice, we find that the gonads originate from a T(+) primitive streak through WT1(+) posterior intermediate mesoderm and appear to share origins anteriorly with the adrenal glands and posteriorly with the metanephric mesenchyme. Comparative single-cell transcriptomic analyses in mouse and cynomolgus monkey embryos reveal the convergence of the lineage trajectory and genetic programs accompanying the specification of biopotential gonadal progenitor cells. This process involves sustained expression of epithelial genes and upregulation of mesenchymal genes, thereby conferring an epithelial-mesenchymal hybrid state. Our study provides key resources for understanding early gonadogenesis in mice and primates.", "classifications": [ { "id": "Yamamoto", "label": "Group Yamamoto", "parent": "Toyoshima", "type": "group" }, { "id": "Toyoshima", "label": "Team Toyoshima", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Kotaro", "last_name": "Sasaki", "name": null }, { "creator_type": "author", "first_name": "Akiko", "last_name": "Oguchi", "name": null }, { "creator_type": "author", "first_name": "Keren", "last_name": "Cheng", "name": null }, { "creator_type": "author", "first_name": "Yasuhiro", "last_name": "Murakawa", "name": null }, { "creator_type": "author", "first_name": "Ikuhiro", "last_name": "Okamoto", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Ohta", "name": null }, { "creator_type": "author", "first_name": "Yukihiro", "last_name": "Yabuta", "name": null }, { "creator_type": "author", "first_name": "Chizuru", "last_name": "Iwatani", "name": null }, { "creator_type": "author", "first_name": "Hideaki", "last_name": "Tsuchiya", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Yasunari", "last_name": "Seita", "name": null }, { "creator_type": "author", "first_name": "Mitinori", "last_name": "Saitou", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.celrep.2021.109075" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "33951437" } }, "mesh": [ { "descriptor": "Adult Stem Cells", "descriptor_ui": "D053687", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Gonads", "descriptor_ui": "D006066", "major_topic": false }, { "descriptor": "Macaca fascicularis", "descriptor_ui": "D008252", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 May 4", "date_precision": "day", "issue": "5", "normalized_date": "2021-05-04", "pages": "109075", "proceedings_title": null, "publisher": "", "title": "Cell reports", "volume": "35", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "The embryonic ontogeny of the gonadal somatic cells in mice and monkeys.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Epithelioid hemangioendothelioma (EHE) is a rare vascular endothelial neoplasm with characteristic histology and distinctive fusion genes. Its clinical presentation and outcome are heterogeneous, and the determinants of survival are controversial. In this study, we aimed to identify clinicopathologic prognostic factors of EHE in a retrospective cohort of 62 cases with CAMTA1/TFE3/WWTR1 alterations. The tumors were of the CAMTA1 subtype for 59 cases, TFE3 subtype for 2 cases, and variant WWTR1 subtype (WWTR1-ACTL6A) for 1 case. Twenty-two tumors (35.5%) demonstrated atypical histology, defined by having at least 2 of the following 3 findings: high mitotic activity (>1/2 mm2), high nuclear grade, and coagulative necrosis. During a median follow-up of 34 months, 11 patients (18%) died, and the 5-year overall survival rate was 78.8%. Survival did not correlate with such clinical parameters as age, sex, tumor sites, multifocality, and multiorgan involvement. Conversely, based on both univariate and multivariate analyses, large tumor size (>30 mm) and histologic atypia were significantly associated with a shorter survival. A proposed 3-tiered risk assessment system using these 2 parameters significantly stratified the patients into low-risk, intermediate-risk, and high-risk groups with 5-year overall survival rates of 100%, 81.8%, and 16.9%, respectively (P<0.001). Four tumors (6.4%) expressed synaptophysin, which all belonged to the high-risk group and pursued an aggressive course. The present study demonstrated the independent prognostic significance of large tumor size and atypical histology in EHE, as well as the value of risk stratification using these 2 factors. Moreover, we revealed a small EHE subset with aberrant synaptophysin expression, which may have potential prognostic and diagnostic implications.", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Takahiro", "last_name": "Shibayama", "name": null }, { "creator_type": "author", "first_name": "Naohiro", "last_name": "Makise", "name": null }, { "creator_type": "author", "first_name": "Toru", "last_name": "Motoi", "name": null }, { "creator_type": "author", "first_name": "Taisuke", "last_name": "Mori", "name": null }, { "creator_type": "author", "first_name": "Nobuyoshi", "last_name": "Hiraoka", "name": null }, { "creator_type": "author", "first_name": "Kan", "last_name": "Yonemori", "name": null }, { "creator_type": "author", "first_name": "Shun-Ichi", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Minoru", "last_name": "Esaki", "name": null }, { "creator_type": "author", "first_name": "Chigusa", "last_name": "Morizane", "name": null }, { "creator_type": "author", "first_name": "Tomotake", "last_name": "Okuma", "name": null }, { "creator_type": "author", "first_name": "Akira", "last_name": "Kawai", "name": null }, { "creator_type": "author", "first_name": "Tetsuo", "last_name": "Ushiku", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null }, { "creator_type": "author", "first_name": "Akihiko", "last_name": "Yoshida", "name": null } ], "identifiers": { "doi": { "normalized": "10.1097/pas.0000000000001660" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "33729740" } }, "mesh": [ { "descriptor": "Adolescent", "descriptor_ui": "D000293", "major_topic": false }, { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Aged, 80 and over", "descriptor_ui": "D000369", "major_topic": false }, { "descriptor": "Biomarkers, Tumor", "descriptor_ui": "D014408", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Hemangioendothelioma, Epithelioid", "descriptor_ui": "D018323", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Immunohistochemistry", "descriptor_ui": "D007150", "major_topic": false }, { "descriptor": "In Situ Hybridization, Fluorescence", "descriptor_ui": "D017404", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Mitosis", "descriptor_ui": "D008938", "major_topic": false }, { "descriptor": "Necrosis", "descriptor_ui": "D009336", "major_topic": false }, { "descriptor": "Neoplasm Grading", "descriptor_ui": "D060787", "major_topic": false }, { "descriptor": "Predictive Value of Tests", "descriptor_ui": "D011237", "major_topic": false }, { "descriptor": "Retrospective Studies", "descriptor_ui": "D012189", "major_topic": false }, { "descriptor": "Risk Assessment", "descriptor_ui": "D018570", "major_topic": false }, { "descriptor": "Risk Factors", "descriptor_ui": "D012307", "major_topic": false }, { "descriptor": "RNA-Seq", "descriptor_ui": "D000081246", "major_topic": false }, { "descriptor": "Synaptophysin", "descriptor_ui": "D016708", "major_topic": false }, { "descriptor": "Time Factors", "descriptor_ui": "D013997", "major_topic": false }, { "descriptor": "Young Adult", "descriptor_ui": "D055815", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 May 1", "date_precision": "day", "issue": "5", "normalized_date": "2021-05-01", "pages": "616-626", "proceedings_title": null, "publisher": "", "title": "The American journal of surgical pathology", "volume": "45", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Clinicopathologic Characterization of Epithelioid Hemangioendothelioma in a Series of 62 Cases: A Proposal of Risk Stratification and Identification of a Synaptophysin-positive Aggressive Subset.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Hydrogen peroxide (H2O2) is one of the main second messengers involved in signaling pathways controlling cell metabolism. During tumorigenesis H2O2 is generated on the extracellular space by membrane-associated NADPH oxidases and superoxide dismutase to stimulate cell proliferation and preservation of the transformed state. Accordingly, a characteristic feature of malignant cells is overproduction of H2O2 in the extracellular milieu and the subsequent absorption in the cytosol. Since the most significant gradients of endogenous extracellular H2O2 can be observed only in a very shallow region of the fluid in contact with the plasma membrane, we show here the use of a newly designed nanosensor anchored to the outer cell surface and capable of quantifying H2O2 at nanometer distance from the membrane proteins responsible for its production. This biosensor is built upon gold nanoparticles functionalized with a H2O2-sensitive boronate compound that is probed using surface enhanced Raman spectroscopy (SERS). The highly localized information obtained on the cell surface by SERS analysis is combined with analytical methods of redox biology to estimate the associated levels of intracellular H2O2 responsible for cell signaling. The results obtained from A549 lung cancer cell line show localized spots on the cell surface at concentration up to 12 muM, associated to intracellular concentration up to 5.1 nM.", "classifications": [ { "id": "Tanaka", "label": "Group Tanaka", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Shigekuni", "last_name": "Hosogi", "name": null }, { "creator_type": "author", "first_name": "Yoshinori", "last_name": "Marunaka", "name": null }, { "creator_type": "author", "first_name": "Eishi", "last_name": "Ashihara", "name": null }, { "creator_type": "author", "first_name": "Tadaaki", "last_name": "Yamada", "name": null }, { "creator_type": "author", "first_name": "Ayumi", "last_name": "Sumino", "name": null }, { "creator_type": "author", "first_name": "Hideo", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Leonardo", "last_name": "Puppulin", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.bios.2021.113077" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "33607416" } }, "mesh": [ { "descriptor": "Biosensing Techniques", "descriptor_ui": "D015374", "major_topic": true }, { "descriptor": "Cell Membrane", "descriptor_ui": "D002462", "major_topic": false }, { "descriptor": "Gold", "descriptor_ui": "D006046", "major_topic": false }, { "descriptor": "Hydrogen Peroxide", "descriptor_ui": "D006861", "major_topic": false }, { "descriptor": "Metal Nanoparticles", "descriptor_ui": "D053768", "major_topic": true }, { "descriptor": "NADPH Oxidases", "descriptor_ui": "D019255", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 May 1", "date_precision": "day", "issue": "", "normalized_date": "2021-05-01", "pages": "113077", "proceedings_title": null, "publisher": "", "title": "Biosensors & bioelectronics", "volume": "179", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Plasma membrane anchored nanosensor for quantifying endogenous production of H2O2 in living cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Fluorescent reporter mouse lines and Cre/Flp recombinase driver lines play essential roles in investigating various molecular functions in vivo. Now that applications of the CRISPR/Cas9 genome-editing system to mouse fertilized eggs have drastically accelerated these knock-in mouse generations, the next need is to establish easier, quicker, and cheaper methods for knock-in donor preparation. Here, we reverify and optimize the phospho-PCR method to obtain highly pure long single-stranded DNAs (ssDNAs) suitable for knock-in mouse generation via genome editing. The sophisticated sequential use of two exonucleases, in which double-stranded DNAs (dsDNAs) amplified by a pair of 5'-phosphorylated primer and normal primer are digested by Lambda exonuclease to yield ssDNA and the following Exonuclease III treatment degrades the remaining dsDNAs, enables much easier long ssDNA productions without laborious gel extraction steps. By microinjecting these donor DNAs along with CRISPR/Cas9 components into mouse zygotes, we have effectively generated fluorescent reporter lines and recombinase drivers. To further broaden the applicability, we have prepared long ssDNA donors in higher concentrations and electroporated them into mouse eggs to successfully obtain knock-in embryos. This classical yet improved method, which is regaining attention on the progress of CRISPR/Cas9 development, shall be the first choice for long donor DNA preparation, and the resulting knock-in lines could accelerate life science research.", "classifications": [ { "id": "Imayoshi", "label": "Group Imayoshi", "parent": "Imayoshi", "type": "group" }, { "id": "Imayoshi", "label": "Team Imayoshi", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yukiko U.", "last_name": "Inoue", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Morimoto", "name": null }, { "creator_type": "author", "first_name": "Mayumi", "last_name": "Yamada", "name": null }, { "creator_type": "author", "first_name": "Ryosuke", "last_name": "Kaneko", "name": null }, { "creator_type": "author", "first_name": "Kazumi", "last_name": "Shimaoka", "name": null }, { "creator_type": "author", "first_name": "Shinji", "last_name": "Oki", "name": null }, { "creator_type": "author", "first_name": "Mayuko", "last_name": "Hotta", "name": null }, { "creator_type": "author", "first_name": "Junko", "last_name": "Asami", "name": null }, { "creator_type": "author", "first_name": "Eriko", "last_name": "Koike", "name": null }, { "creator_type": "author", "first_name": "Kei", "last_name": "Hori", "name": null }, { "creator_type": "author", "first_name": "Mikio", "last_name": "Hoshino", "name": null }, { "creator_type": "author", "first_name": "Itaru", "last_name": "Imayoshi", "name": null }, { "creator_type": "author", "first_name": "Takayoshi", "last_name": "Inoue", "name": null } ], "identifiers": { "doi": { "normalized": "10.3390/cells10051076" }, "pmcid": { "normalized": "PMC8147208" }, "pmid": { "normalized": "33946570" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "CRISPR-Cas Systems", "descriptor_ui": "D064113", "major_topic": false }, { "descriptor": "DNA, Single-Stranded", "descriptor_ui": "D004277", "major_topic": false }, { "descriptor": "Electroporation", "descriptor_ui": "D018274", "major_topic": false }, { "descriptor": "Gene Editing", "descriptor_ui": "D000072669", "major_topic": false }, { "descriptor": "Gene Knock-In Techniques", "descriptor_ui": "D055879", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Transgenic", "descriptor_ui": "D008822", "major_topic": false }, { "descriptor": "Microinjections", "descriptor_ui": "D008845", "major_topic": false }, { "descriptor": "Polymerase Chain Reaction", "descriptor_ui": "D016133", "major_topic": false }, { "descriptor": "Zygote", "descriptor_ui": "D015053", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Apr 30", "date_precision": "day", "issue": "5", "normalized_date": "2021-04-30", "pages": "1076", "proceedings_title": null, "publisher": "", "title": "Cells", "volume": "10", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "An Optimized Preparation Method for Long ssDNA Donors to Facilitate Quick Knock-In Mouse Generation.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Uremic toxins are suggested to be involved in the pathophysiology of hemodialysis (HD) patients. However, the profile of uremic solutes in HD patients has not been fully elucidated. In this study using capillary electrophoresis mass spectrometry (CE-MS), we comprehensively quantified the serum concentrations of 122 ionic solutes before and after HD in 11 patients. In addition, we compared the results with those in non-HD patients with chronic kidney disease (CKD) to identify HD patient-specific solutes. We identified 38 solutes whose concentrations were higher in pre-HD than in CKD stage G5. Ten solutes among them did not significantly accumulate in non-HD CKD patients, suggesting that these solutes accumulate specifically in HD patients. We also identified 23 solutes whose concentrations were lower in both pre- and post-HD than in CKD stage G5. The serum levels of 14 solutes among them were not affected by renal function in non-HD patients, suggesting that these solutes tend to be lost specifically in HD patients. Our data demonstrate that HD patients have a markedly different profile of serum uremic solute levels compared to that in non-HD CKD patients. The solutes identified in our study may contribute to the pathophysiology of HD patients.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yasutoshi", "last_name": "Akiyama", "name": null }, { "creator_type": "author", "first_name": "Koichi", "last_name": "Kikuchi", "name": null }, { "creator_type": "author", "first_name": "Takafumi", "last_name": "Toyohara", "name": null }, { "creator_type": "author", "first_name": "Eikan", "last_name": "Mishima", "name": null }, { "creator_type": "author", "first_name": "Chitose", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Takehiro", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Masaaki", "last_name": "Nakayama", "name": null }, { "creator_type": "author", "first_name": "Yoshihisa", "last_name": "Tomioka", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Takaaki", "last_name": "Abe", "name": null } ], "identifiers": { "doi": { "normalized": "10.3390/toxins13050324" }, "pmcid": { "normalized": "PMC8147146" }, "pmid": { "normalized": "33946481" } }, "mesh": [ { "descriptor": "Case-Control Studies", "descriptor_ui": "D016022", "major_topic": false }, { "descriptor": "Electrophoresis, Capillary", "descriptor_ui": "D019075", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mass Spectrometry", "descriptor_ui": "D013058", "major_topic": false }, { "descriptor": "Metabolome", "descriptor_ui": "D055442", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Renal Dialysis", "descriptor_ui": "D006435", "major_topic": false }, { "descriptor": "Renal Insufficiency, Chronic", "descriptor_ui": "D051436", "major_topic": false }, { "descriptor": "Uremia", "descriptor_ui": "D014511", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Apr 30", "date_precision": "day", "issue": "5", "normalized_date": "2021-04-30", "pages": "", "proceedings_title": null, "publisher": "", "title": "Toxins", "volume": "13", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "CE-MS-Based Identification of Uremic Solutes Specific to Hemodialysis Patients.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Decentralized partially observable Markov decision process (DEC-POMDP) models sequential decision making problems by a team of agents. Since the planning of DEC-POMDP can be interpreted as the maximum likelihood estimation for the latent variable model, DEC-POMDP can be solved by the EM algorithm. However, in EM for DEC-POMDP, the forward-backward algorithm needs to be calculated up to the infinite horizon, which impairs the computational efficiency. In this paper, we propose the Bellman EM algorithm (BEM) and the modified Bellman EM algorithm (MBEM) by introducing the forward and backward Bellman equations into EM. BEM can be more efficient than EM because BEM calculates the forward and backward Bellman equations instead of the forward-backward algorithm up to the infinite horizon. However, BEM cannot always be more efficient than EM when the size of problems is large because BEM calculates an inverse matrix. We circumvent this shortcoming in MBEM by calculating the forward and backward Bellman equations without the inverse matrix. Our numerical experiments demonstrate that the convergence of MBEM is faster than that of EM.", "classifications": [ { "id": "Kobayashi", "label": "Group Kobayashi", "parent": "Wakamoto", "type": "group" }, { "id": "Wakamoto", "label": "Team Wakamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Takehiro", "last_name": "Tottori", "name": null }, { "creator_type": "author", "first_name": "Tetsuya J.", "last_name": "Kobayashi", "name": null } ], "identifiers": { "doi": { "normalized": "10.3390/e23050551" }, "pmcid": { "normalized": "PMC8145255" }, "pmid": { "normalized": "33947054" } }, "mesh": [], "publication": { "conference_name": null, "date": "2021 Apr 29", "date_precision": "day", "issue": "5", "normalized_date": "2021-04-29", "pages": "551", "proceedings_title": null, "publisher": "", "title": "Entropy (Basel, Switzerland)", "volume": "23", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Forward and Backward Bellman Equations Improve the Efficiency of the EM Algorithm for DEC-POMDP.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The increasing number of patients with osteoporosis and sarcopenia is a global concern among countries with progressively aging societies. The high medical costs of treating those patients suggest that prevention rather than treatment is preferable. We enrolled 729 subjects who attended both the second and third surveys of the Research on Osteoarthritis/Osteoporosis Against Disability (ROAD) study. Blood samples were collected from subjects at the second survey, and then a comprehensive metabolomic analysis was performed. It was found that 35 had newly developed osteoporosis at the third survey performed four years later, and 39 were newly diagnosed with sarcopenia at the third survey. In the second survey, we found that serum Gly levels were significantly higher even after adjustment for age, sex, and BMI in subjects with newly developed osteoporosis relative to those who remained osteoporosis-negative during the four-year follow-up. We also show that serum taurine levels were significantly lower at the second survey, even after adjustment for age, sex, and BMI in subjects with newly developed sarcopenia during the four-year follow-up compared with those not diagnosed with sarcopenia at the second or third surveys. Though our sample size and odds ratios were small, increased Gly and decreased taurine levels were found to be predictive of new development of osteoporosis and sarcopenia, respectively, within four years.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Kana", "last_name": "Miyamoto", "name": null }, { "creator_type": "author", "first_name": "Akiyoshi", "last_name": "Hirayama", "name": null }, { "creator_type": "author", "first_name": "Yuiko", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Satsuki", "last_name": "Ikeda", "name": null }, { "creator_type": "author", "first_name": "Midori", "last_name": "Maruyama", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Masaru", "last_name": "Tomita", "name": null }, { "creator_type": "author", "first_name": "Masaya", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Morio", "last_name": "Matsumoto", "name": null }, { "creator_type": "author", "first_name": "Noriko", "last_name": "Yoshimura", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Miyamoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.3390/metabo11050278" }, "pmcid": { "normalized": "PMC8145554" }, "pmid": { "normalized": "33924750" } }, "mesh": [], "publication": { "conference_name": null, "date": "2021 Apr 28", "date_precision": "day", "issue": "5", "normalized_date": "2021-04-28", "pages": "", "proceedings_title": null, "publisher": "", "title": "Metabolites", "volume": "11", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "A Metabolomic Profile Predictive of New Osteoporosis or Sarcopenia Development.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Spontaneous Raman spectroscopy, which senses changes in cellular contents of reduced cytochrome c, could be a powerful tool for label-free evaluation of ischemic hearts. However, undetermined is whether it is applicable to evaluation of myocardial viability in ischemic hearts. To address this issue, we investigated sequential changes in Raman spectra of the subepicardial myocardium in the Langendorff-perfused rat heart before and during ligation of the left coronary artery and its subsequent release and re-ligation. Under 532-nm wavelength excitation, the Raman peak intensity of reduced cytochrome c at 747 cm(-1) increased quickly after the coronary ligation, and reached a quasi-steady state within 30 min. Subsequent reperfusion of the heart after a short-term (30-min) ligation that simulates reversible conditions resulted in quick recovery of the peak intensity to the baseline. Further re-ligation resulted in resurgence of the peak intensity to nearly the identical value to the first ischemia value. In contrast, reperfusion after prolonged (120-min) ligation that assumes irreversible states resulted in incomplete recovery of the peak intensity, and re-ligation resulted in inadequate resurgence. Electron microscopic observations confirmed the spectral findings. Together, the Raman spectroscopic measurement for cytochrome c could be applicable to evaluation of viability of the ischemic myocardium without labeling.", "classifications": [ { "id": "Tanaka", "label": "Group Tanaka", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Koki", "last_name": "Ikemoto", "name": null }, { "creator_type": "author", "first_name": "Kosuke", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Yoshinori", "last_name": "Harada", "name": null }, { "creator_type": "author", "first_name": "Yasuaki", "last_name": "Kumamoto", "name": null }, { "creator_type": "author", "first_name": "Michiyo", "last_name": "Hayakawa", "name": null }, { "creator_type": "author", "first_name": "Kentaro", "last_name": "Mochizuki", "name": null }, { "creator_type": "author", "first_name": "Kazuhiko", "last_name": "Matsuo", "name": null }, { "creator_type": "author", "first_name": "Kenta", "last_name": "Yashiro", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Yaku", "name": null }, { "creator_type": "author", "first_name": "Tetsuro", "last_name": "Takamatsu", "name": null }, { "creator_type": "author", "first_name": "Hideo", "last_name": "Tanaka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1267/ahc.21-00016" }, "pmcid": { "normalized": "PMC8116620" }, "pmid": { "normalized": "34012178" } }, "mesh": [], "publication": { "conference_name": null, "date": "2021 Apr 28", "date_precision": "day", "issue": "2", "normalized_date": "2021-04-28", "pages": "65-72", "proceedings_title": null, "publisher": "", "title": "Acta histochemica et cytochemica", "volume": "54", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Raman Spectroscopic Assessment of Myocardial Viability in Langendorff-Perfused Ischemic Rat Hearts.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Oncogenes often promote cell death as well as proliferation. How oncogenes drive these diametrically opposed phenomena remains to be solved. A key question is whether cell death occurs as a response to aberrant proliferation signals or through a proliferation-independent mechanism. Here, we reveal that Src, the first identified oncogene, simultaneously drives cell proliferation and death in an obligatorily coupled manner through parallel MAPK pathways. The two MAPK pathways diverge from a lynchpin protein Slpr. A MAPK p38 drives proliferation whereas another MAPK JNK drives apoptosis independently of proliferation signals. Src-p38-induced proliferation is regulated by methionine-mediated Tor signaling. Reduction of dietary methionine uncouples the obligatory coupling of cell proliferation and death, suppressing tumorigenesis and tumor-induced lethality. Our findings provide an insight into how cells evolved to have a fail-safe mechanism that thwarts tumorigenesis by the oncogene Src. We also exemplify a diet-based approach to circumvent oncogenesis by exploiting the fail-safe mechanism.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Nishida", "name": null }, { "creator_type": "author", "first_name": "Morihiro", "last_name": "Okada", "name": null }, { "creator_type": "author", "first_name": "Lynna", "last_name": "Yang", "name": null }, { "creator_type": "author", "first_name": "Tomomi", "last_name": "Takano", "name": null }, { "creator_type": "author", "first_name": "Sho", "last_name": "Tabata", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Diana M.", "last_name": "Ho", "name": null }, { "creator_type": "author", "first_name": "Jongkyeong", "last_name": "Chung", "name": null }, { "creator_type": "author", "first_name": "Yasuhiro", "last_name": "Minami", "name": null }, { "creator_type": "author", "first_name": "Sa Kan", "last_name": "Yoo", "name": null } ], "identifiers": { "doi": { "normalized": "10.7554/elife.59809" }, "pmcid": { "normalized": "PMC8079150" }, "pmid": { "normalized": "33902813" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Death", "descriptor_ui": "D016923", "major_topic": true }, { "descriptor": "Cell Proliferation", "descriptor_ui": "D049109", "major_topic": true }, { "descriptor": "Drosophila melanogaster", "descriptor_ui": "D004331", "major_topic": false }, { "descriptor": "Drosophila Proteins", "descriptor_ui": "D029721", "major_topic": false }, { "descriptor": "Larva", "descriptor_ui": "D007814", "major_topic": false }, { "descriptor": "Methionine", "descriptor_ui": "D008715", "major_topic": false }, { "descriptor": "Proto-Oncogene Proteins pp60(c-src)", "descriptor_ui": "D016392", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Apr 27", "date_precision": "day", "issue": "", "normalized_date": "2021-04-27", "pages": "e59809", "proceedings_title": null, "publisher": "", "title": "eLife", "volume": "10", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Methionine restriction breaks obligatory coupling of cell proliferation and death by an oncogene Src in Drosophila.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Large-scale metabolomic studies have become common, and the reliability of the peak data produced by the various instruments is an important issue. However, less attention has been paid to the large number of uncharacterized peaks in untargeted metabolomics data. In this study, we tested various criteria to assess the reliability of 276 and 202 uncharacterized peaks that were detected in a gathered set of 30 plasma and urine quality control samples, respectively, using capillary electrophoresis-time-of-flight mass spectrometry (CE-TOFMS). The linear relationship between the amounts of pooled samples and the corresponding peak areas was one of the criteria used to select reliable peaks. We used samples from approximately 3000 participants in the Tsuruoka Metabolome Cohort Study to investigate patterns of the areas of these uncharacterized peaks among the samples and clustered the peaks by combining the patterns and differences in the migration times. Our assessment pipeline removed substantial numbers of unreliable or redundant peaks and detected 35 and 74 reliable uncharacterized peaks in plasma and urine, respectively, some of which may correspond to metabolites involved in important physiological processes such as disease progression. We propose that our assessment pipeline can be used to help establish large-scale untargeted clinical metabolomic studies.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Rintaro", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Sugimoto", "name": null }, { "creator_type": "author", "first_name": "Akiyoshi", "last_name": "Hirayama", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Masaru", "last_name": "Tomita", "name": null }, { "creator_type": "author", "first_name": "Toru", "last_name": "Takebayashi", "name": null } ], "identifiers": { "doi": { "normalized": "10.3390/jcm10091826" }, "pmcid": { "normalized": "PMC8122759" }, "pmid": { "normalized": "33922230" } }, "mesh": [], "publication": { "conference_name": null, "date": "2021 Apr 22", "date_precision": "day", "issue": "9", "normalized_date": "2021-04-22", "pages": "", "proceedings_title": null, "publisher": "", "title": "Journal of clinical medicine", "volume": "10", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Quality Assessment of Untargeted Analytical Data in a Large-Scale Metabolomic Study.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Hydrogen sulfide (H2S) formed during sulfur metabolism in bacteria has been implicated in the development of intrinsic resistance to antibacterial agents. Despite the conversion of H2S to hydropersulfides greatly enhancing the biochemical properties of H2S such as antioxidant activity, the effects of hydropersulfides on antibiotic resistance have remained unknown. In this work, we investigated the effects of H2S alone or together with cystine to form cysteine hydropersulfide (CysSSH) on the activities of antibacterial agents. By using the disc diffusion test, we found that CysSSH treatment effectively inactivated beta-lactams of the penicillin class (penicillin G and ampicillin) and the carbapenem class (meropenem). These beta-lactams were resistant to treatment with H2S alone or cystine alone. In contrast, cephalosporin class beta-lactams (cefaclor and cefoperazone) and non-beta-lactam antibiotics (tetracycline, kanamycin, erythromycin, and ofloxacin) were stable after CysSSH treatment. Chromatographic and mass spectrometric analyses revealed that CysSSH directly reacted with beta-lactams to form beta-lactam ring-opened carbothioic S-acids (BL-COSH). Furthermore, we demonstrated that certain bacteria (e.g., Escherichia coli and Staphylococcus aureus) efficiently decomposed beta-lactam antibiotics to form BL-COSH, which were transported to the extracellular space. These data suggest that CysSSH-mediated beta-lactam decomposition may contribute to intrinsic bacterial resistance to beta-lactams. BL-COSH may become useful biomarkers for CysSSH-mediated beta-lactam resistance and for investigation of potential antibacterial adjuvants that can enhance the antibacterial activity of beta-lactams by reducing the hydropersulfides in bacteria.", "classifications": [ { "id": "Akaike", "label": "Group Akaike", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Katsuhiko", "last_name": "Ono", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Kitamura", "name": null }, { "creator_type": "author", "first_name": "Tianli", "last_name": "Zhang", "name": null }, { "creator_type": "author", "first_name": "Hiroyasu", "last_name": "Tsutsuki", "name": null }, { "creator_type": "author", "first_name": "Azizur", "last_name": "Rahman", "name": null }, { "creator_type": "author", "first_name": "Toshihiro", "last_name": "Ihara", "name": null }, { "creator_type": "author", "first_name": "Takaaki", "last_name": "Akaike", "name": null }, { "creator_type": "author", "first_name": "Tomohiro", "last_name": "Sawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/acschembio.1c00027" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "33781062" } }, "mesh": [ { "descriptor": "Anti-Bacterial Agents", "descriptor_ui": "D000900", "major_topic": false }, { "descriptor": "Bacteria", "descriptor_ui": "D001419", "major_topic": false }, { "descriptor": "beta-Lactams", "descriptor_ui": "D047090", "major_topic": false }, { "descriptor": "Cyclization", "descriptor_ui": "D003500", "major_topic": false }, { "descriptor": "Sulfides", "descriptor_ui": "D013440", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Apr 16", "date_precision": "day", "issue": "4", "normalized_date": "2021-04-16", "pages": "731-739", "proceedings_title": null, "publisher": "", "title": "ACS chemical biology", "volume": "16", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Cysteine Hydropersulfide Inactivates beta-Lactam Antibiotics with Formation of Ring-Opened Carbothioic S-Acids in Bacteria.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Hepatic fat accumulation is associated with diabetes and hepatocellular carcinoma (HCC). Here, we characterize the metabolic response that high-fat availability elicits in livers before disease development. After a short term on a high-fat diet (HFD), otherwise healthy mice showed elevated hepatic glucose uptake and increased glucose contribution to serine and pyruvate carboxylase activity compared with control diet (CD) mice. This glucose phenotype occurred independently from transcriptional or proteomic programming, which identifies increased peroxisomal and lipid metabolism pathways. HFD-fed mice exhibited increased lactate production when challenged with glucose. Consistently, administration of an oral glucose bolus to healthy individuals revealed a correlation between waist circumference and lactate secretion in a human cohort. In vitro, palmitate exposure stimulated production of reactive oxygen species and subsequent glucose uptake and lactate secretion in hepatocytes and liver cancer cells. Furthermore, HFD enhanced the formation of HCC compared with CD in mice exposed to a hepatic carcinogen. Regardless of the dietary background, all murine tumors showed similar alterations in glucose metabolism to those identified in fat exposed nontransformed mouse livers, however, particular lipid species were elevated in HFD tumor and nontumor-bearing HFD liver tissue. These findings suggest that fat can induce glucose-mediated metabolic changes in nontransformed liver cells similar to those found in HCC. SIGNIFICANCE: With obesity-induced hepatocellular carcinoma on a rising trend, this study shows in normal, nontransformed livers that fat induces glucose metabolism similar to an oncogenic transformation.", "classifications": [ { "id": "Kuroda", "label": "Group Kuroda", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Lindsay A.", "last_name": "Broadfield", "name": null }, { "creator_type": "author", "first_name": "Joao Andre Goncalves", "last_name": "Duarte", "name": null }, { "creator_type": "author", "first_name": "Roberta", "last_name": "Schmieder", "name": null }, { "creator_type": "author", "first_name": "Dorien", "last_name": "Broekaert", "name": null }, { "creator_type": "author", "first_name": "Koen", "last_name": "Veys", "name": null }, { "creator_type": "author", "first_name": "Melanie", "last_name": "Planque", "name": null }, { "creator_type": "author", "first_name": "Kim", "last_name": "Vriens", "name": null }, { "creator_type": "author", "first_name": "Yasuaki", "last_name": "Karasawa", "name": null }, { "creator_type": "author", "first_name": "Francesco", "last_name": "Napolitano", "name": null }, { "creator_type": "author", "first_name": "Suguru", "last_name": "Fujita", "name": null }, { "creator_type": "author", "first_name": "Masashi", "last_name": "Fujii", "name": null }, { "creator_type": "author", "first_name": "Miki", "last_name": "Eto", "name": null }, { "creator_type": "author", "first_name": "Bryan", "last_name": "Holvoet", "name": null }, { "creator_type": "author", "first_name": "Roman", "last_name": "Vangoitsenhoven", "name": null }, { "creator_type": "author", "first_name": "Juan", "last_name": "Fernandez-Garcia", "name": null }, { "creator_type": "author", "first_name": "Joke", "last_name": "Van Elsen", "name": null }, { "creator_type": "author", "first_name": "Jonas", "last_name": "Dehairs", "name": null }, { "creator_type": "author", "first_name": "Jia", "last_name": "Zeng", "name": null }, { "creator_type": "author", "first_name": "James", "last_name": "Dooley", "name": null }, { "creator_type": "author", "first_name": "Rebeca Alba", "last_name": "Rubio", "name": null }, { "creator_type": "author", "first_name": "Jos", "last_name": "van Pelt", "name": null }, { "creator_type": "author", "first_name": "Thomas G. P.", "last_name": "Grunewald", "name": null }, { "creator_type": "author", "first_name": "Adrian", "last_name": "Liston", "name": null }, { "creator_type": "author", "first_name": "Chantal", "last_name": "Mathieu", "name": null }, { "creator_type": "author", "first_name": "Christophe M.", "last_name": "Deroose", "name": null }, { "creator_type": "author", "first_name": "Johannes V.", "last_name": "Swinnen", "name": null }, { "creator_type": "author", "first_name": "Diether", "last_name": "Lambrechts", "name": null }, { "creator_type": "author", "first_name": "Diego", "last_name": "di Bernardo", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Kuroda", "name": null }, { "creator_type": "author", "first_name": "Katrien", "last_name": "De Bock", "name": null }, { "creator_type": "author", "first_name": "Sarah-Maria", "last_name": "Fendt", "name": null } ], "identifiers": { "doi": { "normalized": "10.1158/0008-5472.can-20-1954" }, "pmcid": { "normalized": "PMC7611295" }, "pmid": { "normalized": "33687947" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Carcinoma, Hepatocellular", "descriptor_ui": "D006528", "major_topic": false }, { "descriptor": "Cell Transformation, Neoplastic", "descriptor_ui": "D002471", "major_topic": false }, { "descriptor": "Citric Acid Cycle", "descriptor_ui": "D002952", "major_topic": false }, { "descriptor": "Diet, High-Fat", "descriptor_ui": "D059305", "major_topic": true }, { "descriptor": "Dietary Fats", "descriptor_ui": "D004041", "major_topic": false }, { "descriptor": "Fatty Acids", "descriptor_ui": "D005227", "major_topic": false }, { "descriptor": "Glucose", "descriptor_ui": "D005947", "major_topic": false }, { "descriptor": "Glucose Tolerance Test", "descriptor_ui": "D005951", "major_topic": false }, { "descriptor": "Hepatocytes", "descriptor_ui": "D022781", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Lactic Acid", "descriptor_ui": "D019344", "major_topic": false }, { "descriptor": "Lipid Metabolism", "descriptor_ui": "D050356", "major_topic": false }, { "descriptor": "Liver Neoplasms", "descriptor_ui": "D008113", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Obesity", "descriptor_ui": "D009765", "major_topic": false }, { "descriptor": "Palmitates", "descriptor_ui": "D010168", "major_topic": false }, { "descriptor": "Peroxisomes", "descriptor_ui": "D020675", "major_topic": false }, { "descriptor": "Proteomics", "descriptor_ui": "D040901", "major_topic": false }, { "descriptor": "Pyruvate Carboxylase", "descriptor_ui": "D011766", "major_topic": false }, { "descriptor": "Random Allocation", "descriptor_ui": "D011897", "major_topic": false }, { "descriptor": "Reactive Oxygen Species", "descriptor_ui": "D017382", "major_topic": false }, { "descriptor": "Serine", "descriptor_ui": "D012694", "major_topic": false }, { "descriptor": "Transcriptional Activation", "descriptor_ui": "D015533", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Apr 15", "date_precision": "day", "issue": "8", "normalized_date": "2021-04-15", "pages": "1988-2001", "proceedings_title": null, "publisher": "", "title": "Cancer research", "volume": "81", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Fat Induces Glucose Metabolism in Nontransformed Liver Cells and Promotes Liver Tumorigenesis.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The translation inhibitor rocaglamide A (RocA) has shown promising antitumor activity because it uniquely clamps eukaryotic initiation factor (eIF) 4A onto polypurine RNA for selective translational repression. As eIF4A has been speculated to be a unique target of RocA, alternative targets have not been investigated. Here, we reveal that DDX3 is another molecular target of RocA. Proximity-specific fluorescence labeling of an O-nitrobenzoxadiazole-conjugated derivative revealed that RocA binds to DDX3. RocA clamps the DDX3 protein onto polypurine RNA in an ATP-independent manner. Analysis of a de novo-assembled transcriptome from the plant Aglaia, a natural source of RocA, uncovered the amino acid critical for RocA binding. Moreover, ribosome profiling showed that because of the dominant-negative effect of RocA, high expression of eIF4A and DDX3 strengthens translational repression in cancer cells. This study indicates that sequence-selective clamping of DDX3 and eIF4A, and subsequent dominant-negative translational repression by RocA determine its tumor toxicity.", "classifications": [ { "id": "Sodeoka", "label": "Group Sodeoka", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Mingming", "last_name": "Chen", "name": null }, { "creator_type": "author", "first_name": "Miwako", "last_name": "Asanuma", "name": null }, { "creator_type": "author", "first_name": "Mari", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Yuichi", "last_name": "Shichino", "name": null }, { "creator_type": "author", "first_name": "Mari", "last_name": "Mito", "name": null }, { "creator_type": "author", "first_name": "Koichi", "last_name": "Fujiwara", "name": null }, { "creator_type": "author", "first_name": "Hironori", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Stephen N.", "last_name": "Floor", "name": null }, { "creator_type": "author", "first_name": "Nicholas T.", "last_name": "Ingolia", "name": null }, { "creator_type": "author", "first_name": "Mikiko", "last_name": "Sodeoka", "name": null }, { "creator_type": "author", "first_name": "Kosuke", "last_name": "Dodo", "name": null }, { "creator_type": "author", "first_name": "Takuhiro", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Shintaro", "last_name": "Iwasaki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.chembiol.2020.11.008" }, "pmcid": { "normalized": "PMC8052261" }, "pmid": { "normalized": "33296667" } }, "mesh": [ { "descriptor": "Benzofurans", "descriptor_ui": "D001572", "major_topic": false }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "DEAD-box RNA Helicases", "descriptor_ui": "D053487", "major_topic": false }, { "descriptor": "Enzyme Inhibitors", "descriptor_ui": "D004791", "major_topic": false }, { "descriptor": "Eukaryotic Initiation Factor-4A", "descriptor_ui": "D039601", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Models, Molecular", "descriptor_ui": "D008958", "major_topic": false }, { "descriptor": "Molecular Conformation", "descriptor_ui": "D008968", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Apr 15", "date_precision": "day", "issue": "4", "normalized_date": "2021-04-15", "pages": "475-486.e8", "proceedings_title": null, "publisher": "", "title": "Cell chemical biology", "volume": "28", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Dual targeting of DDX3 and eIF4A by the translation inhibitor rocaglamide A.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The layered structures of graphite and related nanographene molecules play key roles in their physical and electronic functions. However, the stacking modes of negatively curved nanographenes remain unclear, owing to the lack of suitable nanographene molecules. Herein, we report the synthesis and one-dimensional supramolecular self-assembly of negatively curved nanographenes without any assembly-assisting substituents. This curved nanographene self-assembles in various organic solvents and acts as an efficient gelator. The formation of nanofibers was confirmed by microscopic measurements, and an unprecedented double-helix assembly by continuous pi-pi stacking was uncovered by three-dimensional electron crystallography. This work not only reports the discovery of an all-sp(2)-carbon supramolecular pi-organogelator with negative curvature but also demonstrates the power of three-dimensional electron crystallography for the structural determination of submicrometer-sized molecular alignment.", "classifications": [ { "id": "Hijikata", "label": "Group Hijikata", "parent": "Tsuchiya", "type": "group" }, { "id": "Tsuchiya", "label": "Team Tsuchiya", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Kenta", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Kiyofumi", "last_name": "Takaba", "name": null }, { "creator_type": "author", "first_name": "Saori", "last_name": "Maki-Yonekura", "name": null }, { "creator_type": "author", "first_name": "Nobuhiko", "last_name": "Mitoma", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Nakanishi", "name": null }, { "creator_type": "author", "first_name": "Taishi", "last_name": "Nishihara", "name": null }, { "creator_type": "author", "first_name": "Taito", "last_name": "Hatakeyama", "name": null }, { "creator_type": "author", "first_name": "Takuma", "last_name": "Kawada", "name": null }, { "creator_type": "author", "first_name": "Yuh", "last_name": "Hijikata", "name": null }, { "creator_type": "author", "first_name": "Jenny", "last_name": "Pirillo", "name": null }, { "creator_type": "author", "first_name": "Lawrence T.", "last_name": "Scott", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Yonekura", "name": null }, { "creator_type": "author", "first_name": "Yasutomo", "last_name": "Segawa", "name": null }, { "creator_type": "author", "first_name": "Kenichiro", "last_name": "Itami", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/jacs.1c00863" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "33759524" } }, "mesh": [], "publication": { "conference_name": null, "date": "2021 Apr 14", "date_precision": "day", "issue": "14", "normalized_date": "2021-04-14", "pages": "5465-5469", "proceedings_title": null, "publisher": "", "title": "Journal of the American Chemical Society", "volume": "143", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Double-Helix Supramolecular Nanofibers Assembled from Negatively Curved Nanographenes.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Liquid-liquid phase separation (LLPS) plays an important role in a variety of biological processes and is also associated with protein aggregation in neurodegenerative diseases. Quantification of LLPS is necessary to elucidate the mechanism of LLPS and the subsequent aggregation process. In this study, we showed that ataxin-3, which is associated with Machado-Joseph disease, exhibits LLPS in an intracellular crowding environment mimicked by biopolymers, and proposed that a single droplet formed in LLPS can be quantified using Raman microscopy in a label-free manner. We succeeded in evaluating the protein concentration and identifying the components present inside and outside a droplet using the O-H stretching band of water as an internal intensity standard. Only water and protein were detected to be present inside droplets with crowding agents remaining outside. The protein concentration in a droplet was dependent on the crowding environment, indicating that the protein concentration and intracellular environment should be considered when investigating LLPS. Raman microscopy has the potential to become a powerful technique for clarifying the chemical nature of LLPS and its relationship with protein aggregation.", "classifications": [ { "id": "Nakabayashi", "label": "Group Nakabayashi", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Kazuki", "last_name": "Murakami", "name": null }, { "creator_type": "author", "first_name": "Shinji", "last_name": "Kajimoto", "name": null }, { "creator_type": "author", "first_name": "Daiki", "last_name": "Shibata", "name": null }, { "creator_type": "author", "first_name": "Kunisato", "last_name": "Kuroi", "name": null }, { "creator_type": "author", "first_name": "Fumihiko", "last_name": "Fujii", "name": null }, { "creator_type": "author", "first_name": "Takakazu", "last_name": "Nakabayashi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1039/d0sc06095j" }, "pmcid": { "normalized": "PMC8171347" }, "pmid": { "normalized": "34163831" } }, "mesh": [], "publication": { "conference_name": null, "date": "2021 Apr 14", "date_precision": "day", "issue": "21", "normalized_date": "2021-04-14", "pages": "7411-7418", "proceedings_title": null, "publisher": "", "title": "Chemical science", "volume": "12", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Observation of liquid-liquid phase separation of ataxin-3 and quantitative evaluation of its concentration in a single droplet using Raman microscopy.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The use of infrared (IR) photothermal microscopy (IR-PTM) is emerging for imaging chemical substances in various samples. In this research, we demonstrated the use of a nitrile group as a vibrational tag to image target molecules in the low water-background region. We performed IR photothermal imaging of trifluoromethoxy carbonyl cyanide phenylhydrazone (FCCP) in cells and confirmed the high spatial resolution by photothermal detection using visible light as a probe beam. We imaged FCCP-treated HeLa cells and confirmed that the photothermal signal was indeed produced from the vibrational tag in lipid droplets. We also compared the results with nitrile imaging by stimulated Raman scattering (SRS) microscopy. From both the calculated and experimental results, IR-PTM demonstrated a signal-to-noise ratio (SNR) several tens of times better than that of SRS microscopy on the basis of the same power input.", "classifications": [ { "id": "Fujita", "label": "Group Fujita", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Fangfang", "last_name": "Tai", "name": null }, { "creator_type": "author", "first_name": "Kota", "last_name": "Koike", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Kawagoe", "name": null }, { "creator_type": "author", "first_name": "Jun", "last_name": "Ando", "name": null }, { "creator_type": "author", "first_name": "Yasuaki", "last_name": "Kumamoto", "name": null }, { "creator_type": "author", "first_name": "Nicholas I.", "last_name": "Smith", "name": null }, { "creator_type": "author", "first_name": "Mikiko", "last_name": "Sodeoka", "name": null }, { "creator_type": "author", "first_name": "Katsumasa", "last_name": "Fujita", "name": null } ], "identifiers": { "doi": { "normalized": "10.1039/d0an02198a" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "33620044" } }, "mesh": [ { "descriptor": "HeLa Cells", "descriptor_ui": "D006367", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Microscopy", "descriptor_ui": "D008853", "major_topic": true }, { "descriptor": "Nitriles", "descriptor_ui": "D009570", "major_topic": true }, { "descriptor": "Spectrum Analysis, Raman", "descriptor_ui": "D013059", "major_topic": false }, { "descriptor": "Vibration", "descriptor_ui": "D014732", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Apr 7", "date_precision": "day", "issue": "7", "normalized_date": "2021-04-07", "pages": "2307-2312", "proceedings_title": null, "publisher": "", "title": "The Analyst", "volume": "146", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Detecting nitrile-containing small molecules by infrared photothermal microscopy.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "While Delta non-autonomously activates Notch in neighboring cells, it autonomously inactivates Notch through cis-inhibition, the molecular mechanism and biological roles of which remain elusive. The wave of differentiation in the Drosophila brain, the 'proneural wave', is an excellent model for studying Notch signaling in vivo. Here, we show that strong nonlinearity in cis-inhibition reproduces the second peak of Notch activity behind the proneural wave in silico. Based on this, we demonstrate that Delta expression induces a quick degradation of Notch in late endosomes and the formation of the twin peaks of Notch activity in vivo. Indeed, the amount of Notch is upregulated and the twin peaks are fused forming a single peak when the function of Delta or late endosomes is compromised. Additionally, we show that the second Notch peak behind the wavefront controls neurogenesis. Thus, intracellular trafficking of Notch orchestrates the temporal dynamics of Notch activity and the temporal patterning of neurogenesis.", "classifications": [ { "id": "Nagayama", "label": "Group Nagayama", "parent": "Fujiwara", "type": "group" }, { "id": "Fujiwara", "label": "Team Fujiwara", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Miaoxing", "last_name": "Wang", "name": null }, { "creator_type": "author", "first_name": "Xujun", "last_name": "Han", "name": null }, { "creator_type": "author", "first_name": "Chuyan", "last_name": "Liu", "name": null }, { "creator_type": "author", "first_name": "Rie", "last_name": "Takayama", "name": null }, { "creator_type": "author", "first_name": "Tetsuo", "last_name": "Yasugi", "name": null }, { "creator_type": "author", "first_name": "Shin-Ichiro", "last_name": "Ei", "name": null }, { "creator_type": "author", "first_name": "Masaharu", "last_name": "Nagayama", "name": null }, { "creator_type": "author", "first_name": "Yoshitaro", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Sato", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41467-021-22442-3" }, "pmcid": { "normalized": "PMC8027629" }, "pmid": { "normalized": "33828096" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Brain", "descriptor_ui": "D001921", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Drosophila melanogaster", "descriptor_ui": "D004331", "major_topic": false }, { "descriptor": "Drosophila Proteins", "descriptor_ui": "D029721", "major_topic": false }, { "descriptor": "Endosomes", "descriptor_ui": "D011992", "major_topic": false }, { "descriptor": "Gene Expression Regulation, Developmental", "descriptor_ui": "D018507", "major_topic": false }, { "descriptor": "Gene Knockdown Techniques", "descriptor_ui": "D055785", "major_topic": false }, { "descriptor": "Intracellular Signaling Peptides and Proteins", "descriptor_ui": "D047908", "major_topic": false }, { "descriptor": "Neurogenesis", "descriptor_ui": "D055495", "major_topic": false }, { "descriptor": "Protein Transport", "descriptor_ui": "D021381", "major_topic": false }, { "descriptor": "rab GTP-Binding Proteins", "descriptor_ui": "D020691", "major_topic": false }, { "descriptor": "rab4 GTP-Binding Proteins", "descriptor_ui": "D020695", "major_topic": false }, { "descriptor": "rab7 GTP-Binding Proteins", "descriptor_ui": "D000090802", "major_topic": false }, { "descriptor": "Receptors, Notch", "descriptor_ui": "D051880", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Transcription Factors", "descriptor_ui": "D014157", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Apr 7", "date_precision": "day", "issue": "1", "normalized_date": "2021-04-07", "pages": "2083", "proceedings_title": null, "publisher": "", "title": "Nature communications", "volume": "12", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Intracellular trafficking of Notch orchestrates temporal dynamics of Notch activity in the fly brain.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Flexible porous coordination polymers (PCPs)/metal-organic frameworks are unique materials that have potential applications as components of highly efficient separation, sensor, and actuator systems. In general, the structures of flexible PCPs drastically change upon guest loading. In this investigation, we uncovered the rare one-dimensional PCP [Cu(2)(bza)(4)(2-apyr)] (1; bza = benzoate and 2-apyr = 2-aminopyrimidine), which exhibits a unique type of flexibility involving temporary pore opening. Single-crystal X-ray diffraction analysis revealed that desolvated 1 and ethyl acetate (AcOEt)-loaded (1.AcOEt) and CO(2)-loaded (1.CO(2)) 1 have isolated pores. In the case of 1, the pore structure prevents guest penetration. In addition, the isolated pore structures of 1.AcOEt and 1.CO(2) block guest release. However, 1 participates in reversible adsorption/desorption of AcOEt and CO(2) because pore opening occurs temporarily. The CO(2) adsorption/desorption isotherms of 1 are type I and dissimilar to those observed in traditional flexible PCPs with adsorption/desorption hysteresis. The lesser conventional flexibility displayed by 1 could offer new insight into the design of flexible PCPs.", "classifications": [ { "id": "Hijikata", "label": "Group Hijikata", "parent": "Tsuchiya", "type": "group" }, { "id": "Tsuchiya", "label": "Team Tsuchiya", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Shin-Ichiro", "last_name": "Noro", "name": null }, { "creator_type": "author", "first_name": "Yu", "last_name": "Meng", "name": null }, { "creator_type": "author", "first_name": "Kazushige", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Minori", "last_name": "Sugiura", "name": null }, { "creator_type": "author", "first_name": "Yuh", "last_name": "Hijikata", "name": null }, { "creator_type": "author", "first_name": "Jenny", "last_name": "Pirillo", "name": null }, { "creator_type": "author", "first_name": "Xin", "last_name": "Zheng", "name": null }, { "creator_type": "author", "first_name": "Kiyonori", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Takayoshi", "last_name": "Nakamura", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/acs.inorgchem.0c03420" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "33705119" } }, "mesh": [], "publication": { "conference_name": null, "date": "2021 Apr 5", "date_precision": "day", "issue": "7", "normalized_date": "2021-04-05", "pages": "4531-4538", "proceedings_title": null, "publisher": "", "title": "Inorganic chemistry", "volume": "60", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "A Temporarily Pore-Openable Porous Coordination Polymer for Guest Adsorption/Desorption.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Phragmoplasts, which comprise microtubules, actin filaments, and membrane vesicles, are responsible for cell plate formation and expansion during plant cytokinesis. Our previous research using the actin polymerization inhibitor latrunculin B (LatB) to investigate the role of actin filaments suggested the existence of two types of microtubules: 1) initial microtubules sensitive to LatB but unassociated with NACK1 kinesin and 2) later LatB-insensitive, NACK1-associated microtubules. The organization of initial phragmoplast microtubules might have been disrupted by the LatB treatment; this hypothesis remained unverified, however, as the exact timing of cell plate membrane accumulation could not be determined. In the present study, we further investigated the timing of cell plate formation during LatB treatment. We monitored chromosome separation during anaphase as well as accumulation of FM4-64-stained cell plate membranes in dividing transgenic tobacco BY-2 cells expressing RFP-tagged histone H2B. We observed that LatB treatment prolonged the time between the slowdown of daughter chromosome migration and the accumulation of cell plate membranes. This result suggests that disruption of actin filaments resulted in delayed cell plate formation possibly by perturbation of initial phragmoplast microtubules or cell plate assembly.", "classifications": [ { "id": "Higaki", "label": "Group Higaki", "parent": "Ueda", "type": "group" }, { "id": "Ueda", "label": "Team Ueda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Keisho", "last_name": "Maeda", "name": null }, { "creator_type": "author", "first_name": "Takumi", "last_name": "Higaki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1080/15592324.2021.1873586" }, "pmcid": { "normalized": "PMC7971283" }, "pmid": { "normalized": "33427565" } }, "mesh": [ { "descriptor": "Actin Cytoskeleton", "descriptor_ui": "D008841", "major_topic": false }, { "descriptor": "Cell Membrane", "descriptor_ui": "D002462", "major_topic": false }, { "descriptor": "Chromosome Segregation", "descriptor_ui": "D020090", "major_topic": true }, { "descriptor": "Chromosomes, Plant", "descriptor_ui": "D032461", "major_topic": false }, { "descriptor": "Cytokinesis", "descriptor_ui": "D048749", "major_topic": true }, { "descriptor": "Nicotiana", "descriptor_ui": "D014026", "major_topic": false }, { "descriptor": "Time Factors", "descriptor_ui": "D013997", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Apr 3", "date_precision": "day", "issue": "4", "normalized_date": "2021-04-03", "pages": "1873586", "proceedings_title": null, "publisher": "", "title": "Plant signaling & behavior", "volume": "16", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Disruption of actin filaments delays accumulation of cell plate membranes after chromosome separation.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Currently, large-scale cohort studies for metabolome analysis have been launched globally. However, only a few studies have evaluated the reliability of urinary metabolome analysis. This study aimed to establish the reliability of urinary metabolomic profiling in cohort studies. In the Tsuruoka Metabolomics Cohort Study, 123 charged metabolites were identified and routinely quantified using capillary electrophoresis-mass spectrometry (CE-MS). We evaluated approximately 750 quality control (QC) samples and 6,720 participants' spot urine samples. We calculated inter- and intra-batch coefficients of variation in the QC and participant samples and technical intraclass correlation coefficients (ICC). A correlation of metabolite concentrations between spot and 24-h urine samples obtained from 32 sub-cohort participants was also evaluated. The coefficient of variation (CV) was less than 20% for 87 metabolites (70.7%) and 20-30% for 19 metabolites (15.4%) in the QC samples. There was less than 20% inter-batch CV for 106 metabolites (86.2%). Most urinary metabolites would have reliability for measurement. The 96 metabolites (78.0%) was above 0.75 for the estimated ICC, and those might be useful for epidemiological analysis. Among individuals, the Pearson correlation coefficient of 24-h and spot urine was more than 70% for 59 of the 99 metabolites. These results show that the profiling of charged metabolites using CE-MS in morning spot human urine is suitable for epidemiological metabolomics studies.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yoshiki", "last_name": "Ishibashi", "name": null }, { "creator_type": "author", "first_name": "Sei", "last_name": "Harada", "name": null }, { "creator_type": "author", "first_name": "Ayano", "last_name": "Takeuchi", "name": null }, { "creator_type": "author", "first_name": "Miho", "last_name": "Iida", "name": null }, { "creator_type": "author", "first_name": "Ayako", "last_name": "Kurihara", "name": null }, { "creator_type": "author", "first_name": "Suzuka", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Kazuyo", "last_name": "Kuwabara", "name": null }, { "creator_type": "author", "first_name": "Aya", "last_name": "Hirata", "name": null }, { "creator_type": "author", "first_name": "Takuma", "last_name": "Shibuki", "name": null }, { "creator_type": "author", "first_name": "Tomonori", "last_name": "Okamura", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Sugiyama", "name": null }, { "creator_type": "author", "first_name": "Asako", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Kaori", "last_name": "Amano", "name": null }, { "creator_type": "author", "first_name": "Akiyoshi", "last_name": "Hirayama", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Sugimoto", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Masaru", "last_name": "Tomita", "name": null }, { "creator_type": "author", "first_name": "Toru", "last_name": "Takebayashi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41598-021-86600-9" }, "pmcid": { "normalized": "PMC8016858" }, "pmid": { "normalized": "33795760" } }, "mesh": [ { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Biomarkers", "descriptor_ui": "D015415", "major_topic": false }, { "descriptor": "Cohort Studies", "descriptor_ui": "D015331", "major_topic": false }, { "descriptor": "Electrophoresis, Capillary", "descriptor_ui": "D019075", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Japan", "descriptor_ui": "D007564", "major_topic": false }, { "descriptor": "Mass Spectrometry", "descriptor_ui": "D013058", "major_topic": false }, { "descriptor": "Metabolome", "descriptor_ui": "D055442", "major_topic": true }, { "descriptor": "Metabolomics", "descriptor_ui": "D055432", "major_topic": true }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Population Surveillance", "descriptor_ui": "D011159", "major_topic": false }, { "descriptor": "Quality Control", "descriptor_ui": "D011786", "major_topic": false }, { "descriptor": "Urine Specimen Collection", "descriptor_ui": "D059349", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Apr 1", "date_precision": "day", "issue": "1", "normalized_date": "2021-04-01", "pages": "7407", "proceedings_title": null, "publisher": "", "title": "Scientific reports", "volume": "11", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Reliability of urinary charged metabolite concentrations in a large-scale cohort study using capillary electrophoresis-mass spectrometry.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Extracellular vesicles (EVs) released from cancer cells contribute to various malignant phenotypes of cancer, including metastasis, cachexia, and angiogenesis. Although DNA, mRNAs, miRNAs, and proteins contained in EVs have been extensively studied, the function of metabolites in EVs remains unclear. In this study, we performed a comprehensive metabolomic analysis of pancreatic cancer cells, PANC-1, cultured under different oxygen concentrations, and small EVs (sEVs) released from them, considering the fact that hypoxia contributes to the malignant behavior of cells in pancreatic cancer, which is a poorly diagnosed cancer. sEVs were collected by ultracentrifugation, and hydrophilic metabolites were analyzed using capillary ion chromatography-mass spectrometry and liquid chromatography-mass spectrometry, and lipids were analyzed by supercritical fluid chromatography-tandem mass spectrometry. A total of 140 hydrophilic metabolites and 494 lipids were detected in sEVs, and their profiles were different from those in cells. In addition, the metabolomic profile of sEVs was observed to change under hypoxic stress, and an increase in metabolites involved in angiogenesis was also detected. We reveal the hallmark of the metabolites contained in sEVs and the effect of tumor hypoxia on their profiles, which may help in understanding EV-mediated cancer malignancy.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Ryosuke", "last_name": "Hayasaka", "name": null }, { "creator_type": "author", "first_name": "Sho", "last_name": "Tabata", "name": null }, { "creator_type": "author", "first_name": "Masako", "last_name": "Hasebe", "name": null }, { "creator_type": "author", "first_name": "Satsuki", "last_name": "Ikeda", "name": null }, { "creator_type": "author", "first_name": "Sumiko", "last_name": "Ohnuma", "name": null }, { "creator_type": "author", "first_name": "Masaru", "last_name": "Mori", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Masaru", "last_name": "Tomita", "name": null }, { "creator_type": "author", "first_name": "Akiyoshi", "last_name": "Hirayama", "name": null } ], "identifiers": { "doi": { "normalized": "10.3390/metabo11040215" }, "pmcid": { "normalized": "PMC8066639" }, "pmid": { "normalized": "33915936" } }, "mesh": [], "publication": { "conference_name": null, "date": "2021 Apr 1", "date_precision": "day", "issue": "4", "normalized_date": "2021-04-01", "pages": "", "proceedings_title": null, "publisher": "", "title": "Metabolites", "volume": "11", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Metabolomic Analysis of Small Extracellular Vesicles Derived from Pancreatic Cancer Cells Cultured under Normoxia and Hypoxia.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Akihiko", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Taiki", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Eijitsu", "last_name": "Ryo", "name": null }, { "creator_type": "author", "first_name": "Ken-Ichi", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Toru", "last_name": "Motoi", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null }, { "creator_type": "author", "first_name": "Taisuke", "last_name": "Mori", "name": null } ], "identifiers": { "doi": { "normalized": "10.1097/pas.0000000000001627" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "33443863" } }, "mesh": [ { "descriptor": "Antibodies, Monoclonal", "descriptor_ui": "D000911", "major_topic": false }, { "descriptor": "Chondrosarcoma, Mesenchymal", "descriptor_ui": "D018211", "major_topic": true }, { "descriptor": "Homeodomain Proteins", "descriptor_ui": "D018398", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Immunohistochemistry", "descriptor_ui": "D007150", "major_topic": false }, { "descriptor": "In Situ Hybridization", "descriptor_ui": "D017403", "major_topic": false }, { "descriptor": "NFATC Transcription Factors", "descriptor_ui": "D050778", "major_topic": false }, { "descriptor": "Reverse Transcriptase Polymerase Chain Reaction", "descriptor_ui": "D020133", "major_topic": false }, { "descriptor": "RNA", "descriptor_ui": "D012313", "major_topic": false }, { "descriptor": "RNA-Binding Protein EWS", "descriptor_ui": "D034802", "major_topic": false }, { "descriptor": "Sarcoma", "descriptor_ui": "D012509", "major_topic": true }, { "descriptor": "Transcription Factors", "descriptor_ui": "D014157", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Apr 1", "date_precision": "day", "issue": "4", "normalized_date": "2021-04-01", "pages": "578-582", "proceedings_title": null, "publisher": "", "title": "The American journal of surgical pathology", "volume": "45", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Confirmation of NKX3-1 Expression in EWSR1-NFATC2 Sarcoma and Mesenchymal Chondrosarcoma Using Monoclonal Antibody Immunohistochemistry, RT-PCR, and RNA In Situ Hybridization.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The chemotactic network of Escherichia coli has been studied extensively both biophysically and information theoretically. Nevertheless, connection between these two aspects is still elusive. In this work, we report such a connection. We derive an optimal filtering dynamics under the assumption that E. coli's sensory system optimally infers the binary information whether it is swimming up or down along an exponential ligand gradient from noisy sensory signals. Then we show that a standard biochemical model of the chemotactic network is mathematically equivalent to this information-theoretically optimal dynamics. Moreover, we demonstrate that an experimentally observed nonlinear response relation can be reproduced from the optimal dynamics. These results suggest that the biochemical network of E. coli chemotaxis is designed to optimally extract the binary information along an exponential gradient in a noisy condition.", "classifications": [ { "id": "Kobayashi", "label": "Group Kobayashi", "parent": "Wakamoto", "type": "group" }, { "id": "Wakamoto", "label": "Team Wakamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Kento", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Tetsuya J.", "last_name": "Kobayashi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1103/physrevlett.126.128102" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "33834835" } }, "mesh": [ { "descriptor": "Chemotaxis", "descriptor_ui": "D002633", "major_topic": false }, { "descriptor": "Escherichia coli", "descriptor_ui": "D004926", "major_topic": false }, { "descriptor": "Models, Biological", "descriptor_ui": "D008954", "major_topic": true } ], "publication": { "conference_name": null, "date": "2021 Mar 26", "date_precision": "day", "issue": "12", "normalized_date": "2021-03-26", "pages": "128102", "proceedings_title": null, "publisher": "", "title": "Physical review letters", "volume": "126", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Connection between the Bacterial Chemotactic Network and Optimal Filtering.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Prognosis of severe heart failure remains poor. Urgent new therapies are required. Some heart failure patients do not respond to established multidisciplinary treatment and are classified as \"non-responders\". The outcome is especially poor for non-responders, and underlying mechanisms are largely unknown. Mitofusin-1 (Mfn1), a mitochondrial fusion protein, is significantly reduced in non-responding patients. This study aimed to elucidate the role of Mfn1 in the failing heart. Twenty-two idiopathic dilated cardiomyopathy (IDCM) patients who underwent endomyocardial biopsy of intraventricular septum were included. Of the 22 patients, 8 were non-responders (left ventricular (LV) ejection fraction (LVEF) of < 10% improvement at late phase follow-up). Electron microscopy (EM), quantitative PCR, and immunofluorescence studies were performed to explore the biological processes and molecules involved in failure to respond. Studies in cardiac specific Mfn1 knockout mice (c-Mfn1 KO), and in vitro studies with neonatal rat ventricular myocytes (NRVMs) were also conducted. A significant reduction in mitochondrial size in cardiomyocytes, and Mfn1, was observed in non-responders. A LV pressure overload with thoracic aortic constriction (TAC) c-Mfn1 KO mouse model was generated. Systolic function was reduced in c-Mfn1 KO mice, while mitochondria alteration in TAC c-Mfn1 KO mice increased. In vitro studies in NRVMs indicated negative regulation of Mfn1 by the beta-AR/cAMP/PKA/miR-140-5p pathway resulting in significant reduction in mitochondrial respiration of NRVMs. The level of miR140-5p was increased in cardiac tissues of non-responders. Mfn1 is a biomarker of heart failure in non-responders. Therapies targeting mitochondrial dynamics and homeostasis are next generation therapy for non-responding heart failure patients.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yung Ting", "last_name": "Hsiao", "name": null }, { "creator_type": "author", "first_name": "Ippei", "last_name": "Shimizu", "name": null }, { "creator_type": "author", "first_name": "Takayuki", "last_name": "Wakasugi", "name": null }, { "creator_type": "author", "first_name": "Yohko", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Ryutaro", "last_name": "Ikegami", "name": null }, { "creator_type": "author", "first_name": "Yuka", "last_name": "Hayashi", "name": null }, { "creator_type": "author", "first_name": "Masayoshi", "last_name": "Suda", "name": null }, { "creator_type": "author", "first_name": "Goro", "last_name": "Katsuumi", "name": null }, { "creator_type": "author", "first_name": "Masaaki", "last_name": "Nakao", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Ozawa", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Izumi", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Kashimura", "name": null }, { "creator_type": "author", "first_name": "Kazuyuki", "last_name": "Ozaki", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Tohru", "last_name": "Minamino", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41598-021-86209-y" }, "pmcid": { "normalized": "PMC7990924" }, "pmid": { "normalized": "33762690" } }, "mesh": [ { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Biomarkers", "descriptor_ui": "D015415", "major_topic": true }, { "descriptor": "Cardiomyopathy, Dilated", "descriptor_ui": "D002311", "major_topic": false }, { "descriptor": "Disease Models, Animal", "descriptor_ui": "D004195", "major_topic": false }, { "descriptor": "Disease Susceptibility", "descriptor_ui": "D004198", "major_topic": false }, { "descriptor": "Energy Metabolism", "descriptor_ui": "D004734", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Gene Expression", "descriptor_ui": "D015870", "major_topic": false }, { "descriptor": "GTP Phosphohydrolases", "descriptor_ui": "D020558", "major_topic": false }, { "descriptor": "Heart Function Tests", "descriptor_ui": "D006334", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Immunohistochemistry", "descriptor_ui": "D007150", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Mitochondrial Membrane Transport Proteins", "descriptor_ui": "D033681", "major_topic": false }, { "descriptor": "Myocytes, Cardiac", "descriptor_ui": "D032383", "major_topic": false }, { "descriptor": "Organ Specificity", "descriptor_ui": "D009928", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Mar 24", "date_precision": "day", "issue": "1", "normalized_date": "2021-03-24", "pages": "6722", "proceedings_title": null, "publisher": "", "title": "Scientific reports", "volume": "11", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Cardiac mitofusin-1 is reduced in non-responding patients with idiopathic dilated cardiomyopathy.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The discovery and useful application of natural products can help improve human life. Chemicals that inhibit plant growth are broadly utilized as herbicides to control weeds. As various types of herbicides are required, the identification of compounds with novel modes of action is desirable. In the present study, we discovered a novel N-alkoxypyrrole compound, kumamonamide from Streptomyces werraensis MK493-CF1 and established a total synthesis procedure. Resulted in the bioactivity assays, we found that kumamonamic acid, a synthetic intermediate of kumamonamide, is a potential plant growth inhibitor. Further, we developed various derivatives of kumamonamic acid, including a kumamonamic acid nonyloxy derivative (KAND), which displayed high herbicidal activity without adverse effects on HeLa cell growth. We also detected that kumamonamic acid derivatives disturb plant microtubules; and additionally, that KAND affected actin filaments and induced cell death. These multifaceted effects differ from those of known microtubule inhibitors, suggesting a novel mode of action of kumamonamic acid, which represents an important lead for the development of new herbicides.", "classifications": [ { "id": "Higaki", "label": "Group Higaki", "parent": "Ueda", "type": "group" }, { "id": "Ueda", "label": "Team Ueda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Takashi", "last_name": "Ishida", "name": null }, { "creator_type": "author", "first_name": "Haruna", "last_name": "Yoshimura", "name": null }, { "creator_type": "author", "first_name": "Masatsugu", "last_name": "Takekawa", "name": null }, { "creator_type": "author", "first_name": "Takumi", "last_name": "Higaki", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Ideue", "name": null }, { "creator_type": "author", "first_name": "Masaki", "last_name": "Hatano", "name": null }, { "creator_type": "author", "first_name": "Masayuki", "last_name": "Igarashi", "name": null }, { "creator_type": "author", "first_name": "Tokio", "last_name": "Tani", "name": null }, { "creator_type": "author", "first_name": "Shinichiro", "last_name": "Sawa", "name": null }, { "creator_type": "author", "first_name": "Hayato", "last_name": "Ishikawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41598-021-85501-1" }, "pmcid": { "normalized": "PMC7988157" }, "pmid": { "normalized": "33758203" } }, "mesh": [ { "descriptor": "Actins", "descriptor_ui": "D000199", "major_topic": false }, { "descriptor": "Biological Products", "descriptor_ui": "D001688", "major_topic": false }, { "descriptor": "Herbicides", "descriptor_ui": "D006540", "major_topic": false }, { "descriptor": "Microtubules", "descriptor_ui": "D008870", "major_topic": false }, { "descriptor": "Molecular Structure", "descriptor_ui": "D015394", "major_topic": false }, { "descriptor": "Plant Cells", "descriptor_ui": "D059828", "major_topic": false }, { "descriptor": "Plant Development", "descriptor_ui": "D063245", "major_topic": false }, { "descriptor": "Plants", "descriptor_ui": "D010944", "major_topic": false }, { "descriptor": "Streptomyces", "descriptor_ui": "D013302", "major_topic": false }, { "descriptor": "Structure-Activity Relationship", "descriptor_ui": "D013329", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Mar 23", "date_precision": "day", "issue": "1", "normalized_date": "2021-03-23", "pages": "6077", "proceedings_title": null, "publisher": "", "title": "Scientific reports", "volume": "11", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Discovery, characterization and functional improvement of kumamonamide as a novel plant growth inhibitor that disturbs plant microtubules.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Machine learning models for automated magnetic resonance image segmentation may be useful in aiding glioma detection. However, the image differences among facilities cause performance degradation and impede detection. This study proposes a method to solve this issue. We used the data from the Multimodal Brain Tumor Image Segmentation Benchmark (BraTS) and the Japanese cohort (JC) datasets. Three models for tumor segmentation are developed. In our methodology, the BraTS and JC models are trained on the BraTS and JC datasets, respectively, whereas the fine-tuning models are developed from the BraTS model and fine-tuned using the JC dataset. Our results show that the Dice coefficient score of the JC model for the test portion of the JC dataset was 0.779 +/- 0.137, whereas that of the BraTS model was lower (0.717 +/- 0.207). The mean Dice coefficient score of the fine-tuning model was 0.769 +/- 0.138. There was a significant difference between the BraTS and JC models (p < 0.0001) and the BraTS and fine-tuning models (p = 0.002); however, no significant difference between the JC and fine-tuning models (p = 0.673). As our fine-tuning method requires fewer than 20 cases, this method is useful even in a facility where the number of glioma cases is small.", "classifications": [ { "id": "Hamamoto", "label": "Group Hamamoto", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Satoshi", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Masamichi", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Manabu", "last_name": "Kinoshita", "name": null }, { "creator_type": "author", "first_name": "Mototaka", "last_name": "Miyake", "name": null }, { "creator_type": "author", "first_name": "Risa", "last_name": "Kawaguchi", "name": null }, { "creator_type": "author", "first_name": "Naoki", "last_name": "Shinojima", "name": null }, { "creator_type": "author", "first_name": "Akitake", "last_name": "Mukasa", "name": null }, { "creator_type": "author", "first_name": "Kuniaki", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Motoo", "last_name": "Nagane", "name": null }, { "creator_type": "author", "first_name": "Ryohei", "last_name": "Otani", "name": null }, { "creator_type": "author", "first_name": "Fumi", "last_name": "Higuchi", "name": null }, { "creator_type": "author", "first_name": "Shota", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Nobuhiro", "last_name": "Hata", "name": null }, { "creator_type": "author", "first_name": "Kaoru", "last_name": "Tamura", "name": null }, { "creator_type": "author", "first_name": "Kensuke", "last_name": "Tateishi", "name": null }, { "creator_type": "author", "first_name": "Ryo", "last_name": "Nishikawa", "name": null }, { "creator_type": "author", "first_name": "Hideyuki", "last_name": "Arita", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Nonaka", "name": null }, { "creator_type": "author", "first_name": "Takehiro", "last_name": "Uda", "name": null }, { "creator_type": "author", "first_name": "Junya", "last_name": "Fukai", "name": null }, { "creator_type": "author", "first_name": "Yoshiko", "last_name": "Okita", "name": null }, { "creator_type": "author", "first_name": "Naohiro", "last_name": "Tsuyuguchi", "name": null }, { "creator_type": "author", "first_name": "Yonehiro", "last_name": "Kanemura", "name": null }, { "creator_type": "author", "first_name": "Kazuma", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Jun", "last_name": "Sese", "name": null }, { "creator_type": "author", "first_name": "Koichi", "last_name": "Ichimura", "name": null }, { "creator_type": "author", "first_name": "Yoshitaka", "last_name": "Narita", "name": null }, { "creator_type": "author", "first_name": "Ryuji", "last_name": "Hamamoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.3390/cancers13061415" }, "pmcid": { "normalized": "PMC8003655" }, "pmid": { "normalized": "33808802" } }, "mesh": [], "publication": { "conference_name": null, "date": "2021 Mar 19", "date_precision": "day", "issue": "6", "normalized_date": "2021-03-19", "pages": "", "proceedings_title": null, "publisher": "", "title": "Cancers", "volume": "13", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Fine-Tuning Approach for Segmentation of Gliomas in Brain Magnetic Resonance Images with a Machine Learning Method to Normalize Image Differences among Facilities.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Systemic metabolic homeostasis is regulated by inter-organ metabolic cycles involving multiple organs. Obesity impairs inter-organ metabolic cycles, resulting in metabolic diseases. The systemic landscape of dysregulated inter-organ metabolic cycles in obesity has yet to be explored. Here, we measured the transcriptome, proteome, and metabolome in the liver and skeletal muscle and the metabolome in blood of fasted wild-type and leptin-deficient obese (ob/ob) mice, identifying components with differential abundance and differential regulation in ob/ob mice. By constructing and evaluating the trans-omic network controlling the differences in metabolic reactions between fasted wild-type and ob/ob mice, we provided potential mechanisms of the obesity-associated dysfunctions of metabolic cycles between liver and skeletal muscle involving glucose-alanine, glucose-lactate, and ketone bodies. Our study revealed obesity-associated systemic pathological mechanisms of dysfunction of inter-organ metabolic cycles.", "classifications": [ { "id": "Kuroda", "label": "Group Kuroda", "parent": "Kuroda", "type": "group" }, { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Riku", "last_name": "Egami", "name": null }, { "creator_type": "author", "first_name": "Toshiya", "last_name": "Kokaji", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Hatano", "name": null }, { "creator_type": "author", "first_name": "Katsuyuki", "last_name": "Yugi", "name": null }, { "creator_type": "author", "first_name": "Miki", "last_name": "Eto", "name": null }, { "creator_type": "author", "first_name": "Keigo", "last_name": "Morita", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Ohno", "name": null }, { "creator_type": "author", "first_name": "Masashi", "last_name": "Fujii", "name": null }, { "creator_type": "author", "first_name": "Ken-Ichi", "last_name": "Hironaka", "name": null }, { "creator_type": "author", "first_name": "Saori", "last_name": "Uematsu", "name": null }, { "creator_type": "author", "first_name": "Akira", "last_name": "Terakawa", "name": null }, { "creator_type": "author", "first_name": "Yunfan", "last_name": "Bai", "name": null }, { "creator_type": "author", "first_name": "Yifei", "last_name": "Pan", "name": null }, { "creator_type": "author", "first_name": "Takaho", "last_name": "Tsuchiya", "name": null }, { "creator_type": "author", "first_name": "Haruka", "last_name": "Ozaki", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Inoue", "name": null }, { "creator_type": "author", "first_name": "Shinsuke", "last_name": "Uda", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Kubota", "name": null }, { "creator_type": "author", "first_name": "Yutaka", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Masaki", "last_name": "Matsumoto", "name": null }, { "creator_type": "author", "first_name": "Keiichi I.", "last_name": "Nakayama", "name": null }, { "creator_type": "author", "first_name": "Akiyoshi", "last_name": "Hirayama", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Kuroda", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.isci.2021.102217" }, "pmcid": { "normalized": "PMC7961104" }, "pmid": { "normalized": "33748705" } }, "mesh": [], "publication": { "conference_name": null, "date": "2021 Mar 19", "date_precision": "day", "issue": "3", "normalized_date": "2021-03-19", "pages": "102217", "proceedings_title": null, "publisher": "", "title": "iScience", "volume": "24", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Trans-omic analysis reveals obesity-associated dysregulation of inter-organ metabolic cycles between the liver and skeletal muscle.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Advanced-stage gynecologic cancer remains a life-threatening disease. Here, we present a protocol for establishment of stable in vitro 3D spheroid cells derived from human uterine endometrial and ovarian cancer tissues. The tumor-derived spheroid cells have cancer stem cell-related characteristics, including tumorigenesis, and can be used for biological and biochemical analyses and drug efficacy assays. Because these cells possess the biological characteristics of original human tumors, spheroid cells and spheroid-derived xenografts will have applications in personalized medicine in the future. For complete details on the use and execution of this protocol, please refer to Ishiguro et al. (2016) and Mori et al. (2019).", "classifications": [ { "id": "Okamoto", "label": "Group Okamoto", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Haruka", "last_name": "Ueda", "name": null }, { "creator_type": "author", "first_name": "Yutaro", "last_name": "Mori", "name": null }, { "creator_type": "author", "first_name": "Kaoru", "last_name": "Yamawaki", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Ishiguro", "name": null }, { "creator_type": "author", "first_name": "Hirokazu", "last_name": "Ohata", "name": null }, { "creator_type": "author", "first_name": "Ai", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Kentaro", "last_name": "Sugino", "name": null }, { "creator_type": "author", "first_name": "Nozomi", "last_name": "Yachida", "name": null }, { "creator_type": "author", "first_name": "Manako", "last_name": "Yamaguchi", "name": null }, { "creator_type": "author", "first_name": "Kazuaki", "last_name": "Suda", "name": null }, { "creator_type": "author", "first_name": "Ryo", "last_name": "Tamura", "name": null }, { "creator_type": "author", "first_name": "Kosuke", "last_name": "Yoshihara", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Okamoto", "name": null }, { "creator_type": "author", "first_name": "Takayuki", "last_name": "Enomoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.xpro.2021.100354" }, "pmcid": { "normalized": "PMC7905465" }, "pmid": { "normalized": "33665634" } }, "mesh": [ { "descriptor": "Cell Culture Techniques", "descriptor_ui": "D018929", "major_topic": true }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Ovarian Neoplasms", "descriptor_ui": "D010051", "major_topic": true }, { "descriptor": "Spheroids, Cellular", "descriptor_ui": "D018874", "major_topic": true }, { "descriptor": "Tumor Cells, Cultured", "descriptor_ui": "D014407", "major_topic": false }, { "descriptor": "Uterine Neoplasms", "descriptor_ui": "D014594", "major_topic": true } ], "publication": { "conference_name": null, "date": "2021 Mar 19", "date_precision": "day", "issue": "1", "normalized_date": "2021-03-19", "pages": "100354", "proceedings_title": null, "publisher": "", "title": "STAR protocols", "volume": "2", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Establishment of in vitro 3D spheroid cell cultivation from human gynecologic cancer tissues.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Cold atmospheric plasma (CAP) has attracted much attention in the fields of biotechnology and medicine owing to its potential utility in clinical applications. Recently accumulating evidence has demonstrated that CAP influences protein structures. However, there remain open questions regarding the molecular mechanisms behind the CAP-induced structural perturbations of biomacromolecules. Here, we investigated the potential effects of CAP irradiation of amyloid beta (Abeta), an amyloidogenic protein associated with Alzheimer's disease. Using nuclear magnetic resonance spectroscopy, we observed gradual spectral changes in Abeta after a 10 s CAP pretreatment, which also suppressed its fibril formation, as revealed by thioflavin T assay. As per mass spectrometric analyses, these effects were attributed to selective oxidation of the methionine residue (Met) at position 35. Interestingly, this modification occurred when Abeta was dissolved into a pre-irradiated buffer, indicating that some reactive species oxidize the Met residue. Our results strongly suggest that the H(2)O(2) generated in the solution by CAP irradiation is responsible for Met oxidation, which inhibits Abeta amyloid formation. The findings of the present study provide fundamental insights into plasma biology, giving clues for developing novel applications of CAP.", "classifications": [ { "id": "Nishida", "label": "Group Nishida", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Maho", "last_name": "Yagi-Utsumi", "name": null }, { "creator_type": "author", "first_name": "Tomohiro", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Yoko", "last_name": "Otsubo", "name": null }, { "creator_type": "author", "first_name": "Akira", "last_name": "Yamashita", "name": null }, { "creator_type": "author", "first_name": "Shinji", "last_name": "Yoshimura", "name": null }, { "creator_type": "author", "first_name": "Motohiro", "last_name": "Nishida", "name": null }, { "creator_type": "author", "first_name": "Koichi", "last_name": "Kato", "name": null } ], "identifiers": { "doi": { "normalized": "10.3390/ijms22063116" }, "pmcid": { "normalized": "PMC8003251" }, "pmid": { "normalized": "33803786" } }, "mesh": [ { "descriptor": "Amino Acid Sequence", "descriptor_ui": "D000595", "major_topic": false }, { "descriptor": "Amyloid beta-Peptides", "descriptor_ui": "D016229", "major_topic": false }, { "descriptor": "Fluorescence", "descriptor_ui": "D005453", "major_topic": false }, { "descriptor": "Magnetic Resonance Spectroscopy", "descriptor_ui": "D009682", "major_topic": false }, { "descriptor": "Methionine", "descriptor_ui": "D008715", "major_topic": false }, { "descriptor": "Oxidation-Reduction", "descriptor_ui": "D010084", "major_topic": false }, { "descriptor": "Plasma Gases", "descriptor_ui": "D058626", "major_topic": false }, { "descriptor": "Protein Aggregates", "descriptor_ui": "D066329", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Mar 18", "date_precision": "day", "issue": "6", "normalized_date": "2021-03-18", "pages": "", "proceedings_title": null, "publisher": "", "title": "International journal of molecular sciences", "volume": "22", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Cold Atmospheric Plasma Modification of Amyloid beta.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Diacyl peroxides, (RCO2)2, are readily available and widely used reagents for organic synthesis, because they can serve as electrophiles, oxidants, and radical sources. Recently, they have been used extensively as sources of O- and C-functional groups, in contrast to their classical applications as radical initiators. These novel reaction modes have greatly expanded the synthetic utility of diacyl peroxides by making it possible to simultaneously utilize plural functionalities of diacyl peroxides in unprecedented ways, with or without the aid of transition-metal catalysts. Here, we review recent advances in reactions utilizing diacyl peroxides as O- and C-sources, with examples illustrating how the reactivity of diacyl peroxides in organic reactions can be controlled.", "classifications": [ { "id": "Sodeoka", "label": "Group Sodeoka", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Shintaro", "last_name": "Kawamura", "name": null }, { "creator_type": "author", "first_name": "Subrata", "last_name": "Mukherjee", "name": null }, { "creator_type": "author", "first_name": "Mikiko", "last_name": "Sodeoka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1039/d0ob02349c" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "33620360" } }, "mesh": [], "publication": { "conference_name": null, "date": "2021 Mar 18", "date_precision": "day", "issue": "10", "normalized_date": "2021-03-18", "pages": "2096-2109", "proceedings_title": null, "publisher": "", "title": "Organic & biomolecular chemistry", "volume": "19", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Recent advances in reactions using diacyl peroxides as sources of O- and C-functional groups.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Tip-growing fungal cells maintain cell polarity at the apical regions and elongate by de novo synthesis of the cell wall. Cell polarity and tip growth rate affect mycelial morphology. However, it remains unclear how both features act cooperatively to determine cell shape. Here, we investigated this relationship by analyzing hyphal tip growth of filamentous fungi growing inside extremely narrow 1 mum-width channels of microfluidic devices. Since the channels are much narrower than the diameter of hyphae, any hypha growing through the channel must adapt its morphology. Live-cell imaging analyses revealed that hyphae of some species continued growing through the channels, whereas hyphae of other species often ceased growing when passing through the channels, or had lost apical polarity after emerging from the other end of the channel. Fluorescence live-cell imaging analyses of the Spitzenkorper, a collection of secretory vesicles and polarity-related proteins at the hyphal tip, in Neurospora crassa indicates that hyphal tip growth requires a very delicate balance of ordered exocytosis to maintain polarity in spatially confined environments. We analyzed the mycelial growth of seven fungal species from different lineages, including phytopathogenic fungi. This comparative approach revealed that the growth defects induced by the channels were not correlated with their taxonomic classification or with the width of hyphae, but, rather, correlated with the hyphal elongation rate. This report indicates a trade-off between morphological plasticity and velocity in mycelial growth and serves to help understand fungal invasive growth into substrates or plant/animal cells, with direct impact on fungal biotechnology, ecology, and pathogenicity.IMPORTANCE Cell morphology, which is controlled by polarity and growth, is fundamental for all cellular functions. However how polarity and growth act cooperatively to control cell shape remains unclear. Here we investigated their relationship by analyzing hyphal tip growth of filamentous fungi growing inside extremely narrow 1 mum-width channels of microfluidic devices. We found that most fast growing hyphae often lost the cell polarity after emerging from the channels, whereas slow growing hyphae retained polarity and continued growing, indicating a trade-off between plasticity and velocity in mycelial growth. These results serve to understand fungal invasive growth into substrates or plant/animal cells, with direct impact on fungal biotechnology, ecology and pathogenicity.", "classifications": [ { "id": "Sato", "label": "Group Sato", "parent": "Tsuchiya", "type": "group" }, { "id": "Tsuchiya", "label": "Team Tsuchiya", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Sayumi", "last_name": "Fukuda", "name": null }, { "creator_type": "author", "first_name": "Riho", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Naoki", "last_name": "Yanagisawa", "name": null }, { "creator_type": "author", "first_name": "Naoki", "last_name": "Takaya", "name": null }, { "creator_type": "author", "first_name": "Yoshikatsu", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Meritxell", "last_name": "Riquelme", "name": null }, { "creator_type": "author", "first_name": "Norio", "last_name": "Takeshita", "name": null } ], "identifiers": { "doi": { "normalized": "10.1128/mbio.03196-20" }, "pmcid": { "normalized": "PMC8092280" }, "pmid": { "normalized": "33727355" } }, "mesh": [ { "descriptor": "Aspergillus", "descriptor_ui": "D001230", "major_topic": false }, { "descriptor": "Cell Polarity", "descriptor_ui": "D016764", "major_topic": true }, { "descriptor": "Cytoplasm", "descriptor_ui": "D003593", "major_topic": false }, { "descriptor": "Fungal Proteins", "descriptor_ui": "D005656", "major_topic": false }, { "descriptor": "Fungi", "descriptor_ui": "D005658", "major_topic": false }, { "descriptor": "Hyphae", "descriptor_ui": "D025301", "major_topic": false }, { "descriptor": "Microtubules", "descriptor_ui": "D008870", "major_topic": false }, { "descriptor": "Neurospora crassa", "descriptor_ui": "D009492", "major_topic": false }, { "descriptor": "Secretory Vesicles", "descriptor_ui": "D022142", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Mar 16", "date_precision": "day", "issue": "2", "normalized_date": "2021-03-16", "pages": "e03196-20", "proceedings_title": null, "publisher": "", "title": "mBio", "volume": "12", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Trade-off between Plasticity and Velocity in Mycelial Growth.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Neuroendocrine carcinoma of the cervix (NECC) is a rare and highly aggressive tumor with no efficient treatment. We examined genetic features of NECC and identified potential therapeutic targets. A total of 272 patients with cervical cancer (25 NECC, 180 squamous cell carcinoma, 53 adenocarcinoma, and 14 adenosquamous carcinoma) were enrolled. Somatic hotspot mutations in 50 cancer-related genes were detected using the Ion AmpliSeq Cancer Hotspot Panel v2. Human papillomavirus (HPV)-positivity was examined by polymerase chain reaction (PCR)-based testing and in situ hybridization assays. Programmed cell death-ligand 1 (PD-L1) expression was examined using immunohistochemistry. Somatic mutation data for 320 cases of cervical cancer from the Project GENIE database were also analyzed. NECC showed similar (PIK3CA, 32%; TP53, 24%) and distinct (SMAD4, 20%; RET, 16%; EGFR, 12%; APC, 12%) alterations compared with other histological types. The GENIE cohort had similar profiles and RB1 mutations in 27.6% of NECC cases. Eleven (44%) cases had at least one actionable mutation linked to molecular targeted therapies and 14 (56%) cases showed more than one combined positive score for PD-L1 expression. HPV-positivity was observed in all NECC cases with a predominance of HPV-18. We report specific gene mutation profiles for NECC, which can provide a basis for the development of novel therapeutic strategies.", "classifications": [ { "id": "Hamamoto", "label": "Group Hamamoto", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Daisuke", "last_name": "Takayanagi", "name": null }, { "creator_type": "author", "first_name": "Sou", "last_name": "Hirose", "name": null }, { "creator_type": "author", "first_name": "Ikumi", "last_name": "Kuno", "name": null }, { "creator_type": "author", "first_name": "Yuka", "last_name": "Asami", "name": null }, { "creator_type": "author", "first_name": "Naoya", "last_name": "Murakami", "name": null }, { "creator_type": "author", "first_name": "Maiko", "last_name": "Matsuda", "name": null }, { "creator_type": "author", "first_name": "Yoko", "last_name": "Shimada", "name": null }, { "creator_type": "author", "first_name": "Kuniko", "last_name": "Sunami", "name": null }, { "creator_type": "author", "first_name": "Masaaki", "last_name": "Komatsu", "name": null }, { "creator_type": "author", "first_name": "Ryuji", "last_name": "Hamamoto", "name": null }, { "creator_type": "author", "first_name": "Mayumi Kobayashi", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Matsumoto", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Kohno", "name": null }, { "creator_type": "author", "first_name": "Tomoyasu", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Kouya", "last_name": "Shiraishi", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Yoshida", "name": null } ], "identifiers": { "doi": { "normalized": "10.3390/cancers13061215" }, "pmcid": { "normalized": "PMC8001835" }, "pmid": { "normalized": "33802174" } }, "mesh": [], "publication": { "conference_name": null, "date": "2021 Mar 10", "date_precision": "day", "issue": "6", "normalized_date": "2021-03-10", "pages": "", "proceedings_title": null, "publisher": "", "title": "Cancers", "volume": "13", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Comparative Analysis of Genetic Alterations, HPV-Status, and PD-L1 Expression in Neuroendocrine Carcinomas of the Cervix.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Recurrent C11orf95-RELA fusions (RELA(FUS)) are the hallmark of supratentorial ependymomas. The presence of RELA as the fusion partner indicates a close association of aberrant NF-kappaB activity with tumorigenesis. However, the oncogenic role of the C11orf95 has not been determined. Here, we performed ChIP-seq analyses to explore genomic regions bound by RELA(FUS) and H3K27ac proteins in human 293T and mouse ependymoma cells. We then utilized published RNA-Seq data from human and mouse RELA(FUS) tumors and identified target genes that were directly regulated by RELA(FUS) in these tumors. Subsequent transcription factor motif analyses of RELA(FUS) target genes detected a unique GC-rich motif recognized by the C11orf95 moiety, that is present in approximately half of RELA(FUS) target genes. Luciferase assays confirmed that a promoter carrying this motif is sufficient to drive RELA(FUS)-dependent gene expression. Further, the RELA(FUS) target genes were found to be overlapped with Rela target genes primarily via non-canonical NF-kappaB binding sites. Using a series of truncation and substitution mutants of RELA(FUS), we also show that the activation domain in the RELA(FUS) moiety is necessary for the regulation of gene expression of these RELA(FUS) target genes. Lastly, we performed an anti-cancer drug screening with mouse ependymoma cells and identified potential anti-ependymoma drugs that are related to the oncogenic mechanism of RELA(FUS). These findings suggested that RELA(FUS) might induce ependymoma formation through oncogenic pathways orchestrated by both C11orf95 and RELA target genes. Thus, our study unveils a complex gene function of RELA(FUS) as an oncogenic transcription factor in RELA(FUS) positive ependymomas.", "classifications": [ { "id": "Hamamoto", "label": "Group Hamamoto", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Ozawa", "name": null }, { "creator_type": "author", "first_name": "Syuzo", "last_name": "Kaneko", "name": null }, { "creator_type": "author", "first_name": "Frank", "last_name": "Szulzewsky", "name": null }, { "creator_type": "author", "first_name": "Zhiwei", "last_name": "Qiao", "name": null }, { "creator_type": "author", "first_name": "Mutsumi", "last_name": "Takadera", "name": null }, { "creator_type": "author", "first_name": "Yoshitaka", "last_name": "Narita", "name": null }, { "creator_type": "author", "first_name": "Tadashi", "last_name": "Kondo", "name": null }, { "creator_type": "author", "first_name": "Eric C.", "last_name": "Holland", "name": null }, { "creator_type": "author", "first_name": "Ryuji", "last_name": "Hamamoto", "name": null }, { "creator_type": "author", "first_name": "Koichi", "last_name": "Ichimura", "name": null } ], "identifiers": { "doi": { "normalized": "10.1186/s40478-021-01135-4" }, "pmcid": { "normalized": "PMC7941712" }, "pmid": { "normalized": "33685520" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Brain Neoplasms", "descriptor_ui": "D001932", "major_topic": false }, { "descriptor": "DNA-Binding Proteins", "descriptor_ui": "D004268", "major_topic": false }, { "descriptor": "Ependymoma", "descriptor_ui": "D004806", "major_topic": false }, { "descriptor": "Epigenesis, Genetic", "descriptor_ui": "D044127", "major_topic": true }, { "descriptor": "Gene Expression", "descriptor_ui": "D015870", "major_topic": false }, { "descriptor": "Gene Expression Regulation", "descriptor_ui": "D005786", "major_topic": false }, { "descriptor": "Genetic Techniques", "descriptor_ui": "D005821", "major_topic": false }, { "descriptor": "HEK293 Cells", "descriptor_ui": "D057809", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "NF-kappa B", "descriptor_ui": "D016328", "major_topic": false }, { "descriptor": "Oncogene Proteins, Fusion", "descriptor_ui": "D015514", "major_topic": false }, { "descriptor": "Proteins", "descriptor_ui": "D011506", "major_topic": false }, { "descriptor": "Supratentorial Neoplasms", "descriptor_ui": "D015173", "major_topic": false }, { "descriptor": "Transcription Factor RelA", "descriptor_ui": "D051996", "major_topic": false }, { "descriptor": "Transcription Factors", "descriptor_ui": "D014157", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Mar 8", "date_precision": "day", "issue": "1", "normalized_date": "2021-03-08", "pages": "36", "proceedings_title": null, "publisher": "", "title": "Acta neuropathologica communications", "volume": "9", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "C11orf95-RELA fusion drives aberrant gene expression through the unique epigenetic regulation for ependymoma formation.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The extraction of cellular contents from plant cells covered with cell walls remains a challenge, as it is physically hindered by the cell wall. We present a new microfluidic approach that leverages an intense pulsed electric field for permeabilizing the cell wall and a focused DC electric field for extracting the cellular contents selectively from a few targeted cells in a cluster of intact plant cells. We coupled the approach with on-chip fluorescence quantification of extracted molecules leveraging isotachophoresis as well as off-chip reverse transcription-quantitative polymerase chain reaction detecting extracted mRNA molecules. Our approach offers a workflow of about 5 min, isolating a cluster of intact plant cells, permeabilizing the cell wall, selectively extracting cytosolic molecules from a few targeted cells in the cluster, and outputting them to off-chip analyses without any enzymatic reactions. We anticipate that this approach will create a new opportunity to explore plant biology through less biased data realized by the rapid extraction of molecules from intact plant clusters.", "classifications": [ { "id": "Shintaku", "label": "Group Shintaku", "parent": "Shintaku", "type": "group" }, { "id": "Shintaku", "label": "Team Shintaku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Sangamithirai", "last_name": "Subramanian Parimalam", "name": null }, { "creator_type": "author", "first_name": "Mahmoud Nady", "last_name": "Abdelmoez", "name": null }, { "creator_type": "author", "first_name": "Arata", "last_name": "Tsuchida", "name": null }, { "creator_type": "author", "first_name": "Naoyuki", "last_name": "Sotta", "name": null }, { "creator_type": "author", "first_name": "Mayuki", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Kuromori", "name": null }, { "creator_type": "author", "first_name": "Toru", "last_name": "Fujiwara", "name": null }, { "creator_type": "author", "first_name": "Masami Yokota", "last_name": "Hirai", "name": null }, { "creator_type": "author", "first_name": "Ryuji", "last_name": "Yokokawa", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Oguchi", "name": null }, { "creator_type": "author", "first_name": "Hirofumi", "last_name": "Shintaku", "name": null } ], "identifiers": { "doi": { "normalized": "10.1039/d0an02163f" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "33624642" } }, "mesh": [ { "descriptor": "Cell Wall", "descriptor_ui": "D002473", "major_topic": false }, { "descriptor": "Isotachophoresis", "descriptor_ui": "D057625", "major_topic": true }, { "descriptor": "Microfluidics", "descriptor_ui": "D044085", "major_topic": false }, { "descriptor": "Oligonucleotide Array Sequence Analysis", "descriptor_ui": "D020411", "major_topic": false }, { "descriptor": "Plants", "descriptor_ui": "D010944", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Mar 7", "date_precision": "day", "issue": "5", "normalized_date": "2021-03-07", "pages": "1604-1611", "proceedings_title": null, "publisher": "", "title": "The Analyst", "volume": "146", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Targeted permeabilization of the cell wall and extraction of charged molecules from single cells in intact plant clusters using a focused electric field.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "A notable example of spiral architecture in organs is the mammalian cochlear duct, where the morphology is critical for hearing function. Genetic studies have revealed necessary signaling molecules, but it remains unclear how cellular dynamics generate elongating, bending, and coiling of the cochlear duct. Here, we show that extracellular signal-regulated kinase (ERK) activation waves control collective cell migration during the murine cochlear duct development using deep tissue live-cell imaging, Forster resonance energy transfer (FRET)-based quantitation, and mathematical modeling. Long-term FRET imaging reveals that helical ERK activation propagates from the apex duct tip concomitant with the reverse multicellular flow on the lateral side of the developing cochlear duct, resulting in advection-based duct elongation. Moreover, model simulations, together with experiments, explain that the oscillatory wave trains of ERK activity and the cell flow are generated by mechanochemical feedback. Our findings propose a regulatory mechanism to coordinate the multicellular behaviors underlying the duct elongation during development.", "classifications": [], "creators": [ { "creator_type": "author", "first_name": "Mamoru", "last_name": "Ishii", "name": null }, { "creator_type": "author", "first_name": "Tomoko", "last_name": "Tateya", "name": null }, { "creator_type": "author", "first_name": "Michiyuki", "last_name": "Matsuda", "name": null }, { "creator_type": "author", "first_name": "Tsuyoshi", "last_name": "Hirashima", "name": null } ], "identifiers": { "doi": { "normalized": "10.7554/elife.61092" }, "pmcid": { "normalized": "PMC7935486" }, "pmid": { "normalized": "33667159" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Movement", "descriptor_ui": "D002465", "major_topic": true }, { "descriptor": "Cochlear Duct", "descriptor_ui": "D003053", "major_topic": false }, { "descriptor": "Embryo, Mammalian", "descriptor_ui": "D004622", "major_topic": false }, { "descriptor": "Fluorescence Resonance Energy Transfer", "descriptor_ui": "D031541", "major_topic": false }, { "descriptor": "MAP Kinase Signaling System", "descriptor_ui": "D020935", "major_topic": true }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred ICR", "descriptor_ui": "D008813", "major_topic": false }, { "descriptor": "Mice, Transgenic", "descriptor_ui": "D008822", "major_topic": false }, { "descriptor": "Models, Theoretical", "descriptor_ui": "D008962", "major_topic": false }, { "descriptor": "Morphogenesis", "descriptor_ui": "D009024", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Mar 5", "date_precision": "day", "issue": "", "normalized_date": "2021-03-05", "pages": "e61092", "proceedings_title": null, "publisher": "", "title": "eLife", "volume": "10", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Retrograde ERK activation waves drive base-to-apex multicellular flow in murine cochlear duct morphogenesis.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Heterogeneous nuclear ribonucleoprotein K (hnRNPK) transcripts are abundant in estrogen receptor (ER)- or progesterone receptor (PR)-positive breast cancer. However, the biological functions of hnRNPK in the ER-mediated signaling pathway have remained largely unknown. Therefore, this study analyzes the functions of hnRNPK expression in the ER-mediated signaling pathway in breast cancer. We initially evaluated hnRNPK expression upon treatment with estradiol (E2) and ICI 182,780 in the ERα-positive breast carcinoma cell line MCF-7. The results revealed that E2 increased hnRNPK; however, hnRNPK expression was decreased with ICI 182,780 treatment, indicating estrogen dependency. We further evaluated the effects of hnRNPK knockdown in the ER-mediated signaling pathway in MCF-7 cells using small interfering RNAs. The results revealed that hnRNPK knockdown decreased ERα expression and ERα target gene pS2 by E2 treatment. As hnRNPK interacts with several other proteins, we explored the interaction between hnRNPK and ERα, which was demonstrated using immunoprecipitation and proximity ligation assay. Subsequently, we immunolocalized hnRNPK in patients with breast cancer, which revealed that hnRNPK immunoreactivity was significantly higher in ERα-positive carcinoma cells and significantly lower in Ki67-positive or proliferative carcinoma cells. These results indicated that hnRNPK directly interacted with ERα and was involved in the ER-mediated signaling pathway in breast carcinoma. Furthermore, hnRNPK expression could be an additional target of endocrine therapy in patients with ERα-positive breast cancer.", "classifications": [ { "id": "Suzuki", "label": "Group Suzuki", "parent": "Takekawa", "type": "group" }, { "id": "Takekawa", "label": "Team Takekawa", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Erina", "last_name": "Iwabuchi", "name": null }, { "creator_type": "author", "first_name": "Yasuhiro", "last_name": "Miki", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Hisashi", "last_name": "Hirakawa", "name": null }, { "creator_type": "author", "first_name": "Takanori", "last_name": "Ishida", "name": null }, { "creator_type": "author", "first_name": "Hironobu", "last_name": "Sasano", "name": null } ], "identifiers": { "doi": { "normalized": "10.3390/ijms22052581" }, "pmcid": { "normalized": "PMC7962001" }, "pmid": { "normalized": "33806648" } }, "mesh": [ { "descriptor": "Breast Neoplasms", "descriptor_ui": "D001943", "major_topic": false }, { "descriptor": "Carcinoma", "descriptor_ui": "D002277", "major_topic": false }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Cell Proliferation", "descriptor_ui": "D049109", "major_topic": false }, { "descriptor": "Estrogens", "descriptor_ui": "D004967", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Gene Expression Regulation, Neoplastic", "descriptor_ui": "D015972", "major_topic": false }, { "descriptor": "Heterogeneous-Nuclear Ribonucleoprotein K", "descriptor_ui": "D034641", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "MCF-7 Cells", "descriptor_ui": "D061986", "major_topic": false }, { "descriptor": "Receptors, Estrogen", "descriptor_ui": "D011960", "major_topic": false }, { "descriptor": "RNA, Small Interfering", "descriptor_ui": "D034741", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Mar 4", "date_precision": "day", "issue": "5", "normalized_date": "2021-03-04", "pages": "", "proceedings_title": null, "publisher": "", "title": "International journal of molecular sciences", "volume": "22", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Heterogeneous Nuclear Ribonucleoprotein K Is Involved in the Estrogen-Signaling Pathway in Breast Cancer.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "gamma-Linolenic acid (GLA) is reported to show tumor-selective cytotoxicity through unidentified mechanisms. Here, to assess the involvement of oxidized metabolites of GLA, we synthesized several deuterated GLAs and evaluated their metabolism and cytotoxicity towards normal human fibroblast WI-38 cells and VA-13 tumor cells generated from WI-38 by transformation with SV40 virus. Deuteration of GLA suppressed both metabolism and cytotoxicity towards WI-38 cells and increased the selectivity for VA-13 cells. Fully deuterated GLA was visualized by Raman imaging, which indicated that GLA is accumulated in intracellular lipid droplets of VA-13 cells. Our results suggest the tumor-selective cytotoxicity is due to GLA itself, not its oxidized metabolites.", "classifications": [ { "id": "Sodeoka", "label": "Group Sodeoka", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Kosuke", "last_name": "Dodo", "name": null }, { "creator_type": "author", "first_name": "Ayato", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Tamura", "name": null }, { "creator_type": "author", "first_name": "Syusuke", "last_name": "Egoshi", "name": null }, { "creator_type": "author", "first_name": "Koichi", "last_name": "Fujiwara", "name": null }, { "creator_type": "author", "first_name": "Kana", "last_name": "Oonuma", "name": null }, { "creator_type": "author", "first_name": "Shuhei", "last_name": "Nakao", "name": null }, { "creator_type": "author", "first_name": "Naoki", "last_name": "Terayama", "name": null }, { "creator_type": "author", "first_name": "Mikiko", "last_name": "Sodeoka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1039/d0cc07824g" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "33527102" } }, "mesh": [ { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "Cell Survival", "descriptor_ui": "D002470", "major_topic": false }, { "descriptor": "Deuterium", "descriptor_ui": "D003903", "major_topic": false }, { "descriptor": "Fibroblasts", "descriptor_ui": "D005347", "major_topic": false }, { "descriptor": "gamma-Linolenic Acid", "descriptor_ui": "D017965", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Molecular Structure", "descriptor_ui": "D015394", "major_topic": false }, { "descriptor": "Spectrum Analysis, Raman", "descriptor_ui": "D013059", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Mar 1", "date_precision": "day", "issue": "17", "normalized_date": "2021-03-01", "pages": "2180-2183", "proceedings_title": null, "publisher": "", "title": "Chemical communications (Cambridge, England)", "volume": "57", "year": 2021 }, "ssbd": { "database": [ "ssbd-database-000222" ], "repository": [ "ssbd-repos-000222" ] }, "title": "Synthesis of deuterated gamma-linolenic acid and application for biological studies: metabolic tuning and Raman imaging.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Organ morphologies are diverse but also conserved under shared developmental constraints among species. Any geometrical similarities in the shape behind diversity and the underlying developmental constraints remain unclear. Plant root tip outlines commonly exhibit a dome shape, which likely performs physiological functions, despite the diversity in size and cellular organization among distinct root classes and/or species. We carried out morphometric analysis of the primary roots of ten angiosperm species and of the lateral roots (LRs) of Arabidopsis, and found that each root outline was isometrically scaled onto a parameter-free catenary curve, a stable structure adopted for arch bridges. Using the physical model for bridges, we analogized that localized and spatially uniform occurrence of oriented cell division and expansion force the LR primordia (LRP) tip to form a catenary curve. These growth rules for the catenary curve were verified by tissue growth simulation of developing LRP development based on time-lapse imaging. Consistently, LRP outlines of mutants compromised in these rules were found to deviate from catenary curves. Our analyses demonstrate that physics-inspired growth rules constrain plant root tips to form isometrically scalable catenary curves.", "classifications": [ { "id": "Fujimoto", "label": "Group Fujimoto", "parent": "Ueda", "type": "group" }, { "id": "Ueda", "label": "Team Ueda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Motohiro", "last_name": "Fujiwara", "name": null }, { "creator_type": "author", "first_name": "Tatsuaki", "last_name": "Goh", "name": null }, { "creator_type": "author", "first_name": "Satoru", "last_name": "Tsugawa", "name": null }, { "creator_type": "author", "first_name": "Keiji", "last_name": "Nakajima", "name": null }, { "creator_type": "author", "first_name": "Hidehiro", "last_name": "Fukaki", "name": null }, { "creator_type": "author", "first_name": "Koichi", "last_name": "Fujimoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1242/dev.196253" }, "pmcid": { "normalized": "PMC7929931" }, "pmid": { "normalized": "33637613" } }, "mesh": [ { "descriptor": "Arabidopsis", "descriptor_ui": "D017360", "major_topic": false }, { "descriptor": "Cell Division", "descriptor_ui": "D002455", "major_topic": false }, { "descriptor": "Meristem", "descriptor_ui": "D018519", "major_topic": false }, { "descriptor": "Plant Development", "descriptor_ui": "D063245", "major_topic": false }, { "descriptor": "Plant Roots", "descriptor_ui": "D018517", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Feb 26", "date_precision": "day", "issue": "4", "normalized_date": "2021-02-26", "pages": "dev196253", "proceedings_title": null, "publisher": "", "title": "Development (Cambridge, England)", "volume": "148", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Tissue growth constrains root organ outlines into an isometrically scalable shape.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Marine invertebrate larvae are known to begin metamorphosis in response to environmentally derived cues. However, little is known about the relationships between the perception of such cues and internal signalling for metamorphosis. To elucidate the mechanism underlying the initiation of metamorphosis in the ascidian, Ciona intestinalis type A (Ciona robusta), we artificially induced ascidian metamorphosis and investigated Ca(2+) dynamics from pre- to post-metamorphosis. Ca(2+) transients were observed and consisted of two temporally distinct phases with different durations before tail regression which is the early event of metamorphosis. In the first phase, Phase I, the Ca(2+) transient in the papillae (adhesive organ of the anterior trunk) was coupled with the Ca(2+) transient in dorsally localized cells and endoderm cells just after mechanical stimulation. The Ca(2+) transients in Phase I were also observed when applying only short stimulation. In the second phase, Phase II, the Ca(2+) transient in papillae was observed again and lasted for approximately 5-11 min just after the Ca(2+) transient in Phase I continued for a few minutes. The impaired papillae by Foxg-knockdown failed to induce the second Ca(2+) transient in Phase II and tail regression. In Phase II, a wave-like Ca(2+) propagation was also observed across the entire epidermis. Our results indicate that the papillae sense a mechanical cue and two-round Ca(2+) transients in papillae transmits the internal metamorphic signals to different tissues, which subsequently induces tail regression. Our study will help elucidate the internal mechanism of metamorphosis in marine invertebrate larvae in response to environmental cues.", "classifications": [ { "id": "Sawai", "label": "Group Sawai", "parent": "Sawai", "type": "group" }, { "id": "Sawai", "label": "Team Sawai", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Maiki K.", "last_name": "Wakai", "name": null }, { "creator_type": "author", "first_name": "Mitsuru J.", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Sawai", "name": null }, { "creator_type": "author", "first_name": "Kohji", "last_name": "Hotta", "name": null }, { "creator_type": "author", "first_name": "Kotaro", "last_name": "Oka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1098/rspb.2020.3207" }, "pmcid": { "normalized": "PMC7935057" }, "pmid": { "normalized": "33593191" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Ciona intestinalis", "descriptor_ui": "D002938", "major_topic": true }, { "descriptor": "Epidermis", "descriptor_ui": "D004817", "major_topic": false }, { "descriptor": "Larva", "descriptor_ui": "D007814", "major_topic": false }, { "descriptor": "Metamorphosis, Biological", "descriptor_ui": "D008675", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Feb 24", "date_precision": "day", "issue": "1945", "normalized_date": "2021-02-24", "pages": "20203207", "proceedings_title": null, "publisher": "", "title": "Proceedings. Biological sciences", "volume": "288", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Two-Round Ca(2+) transient in papillae by mechanical stimulation induces metamorphosis in the ascidian Ciona intestinalis type A.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Glycoconjugates are an important class of biomolecules that regulate numerous biological events in cells. However, these complex, medium-size molecules are metabolically unstable, which hampers detailed investigations of their functions as well as their potential application as pharmaceuticals. Here we report sialidase-resistant analogues of ganglioside GM3 containing a monofluoromethylene linkage instead of the native O-sialoside linkage. Stereoselective synthesis of CHF-linked disaccharides and kinetically controlled Au(I)-catalyzed glycosylation efficiently furnished both stereoisomers of CHF-linked as well as CF 2 - and CH 2 -linked GM3 analogues. Like native GM3, the C-linked GM3 analogues inhibited the autophosphorylation of epidermal growth factor (EGF) receptor induced by EGF in vitro. Assay of the proliferation-enhancing activity toward Had-1 cells together with NMR-based conformational analysis showed that the (S)-CHF-linked GM3 analogue with exo-gauche conformation is the most potent of the synthesized compounds. Our findings suggest that exo-anomeric conformation is important for the biological functions of GM3.", "classifications": [ { "id": "Sodeoka", "label": "Group Sodeoka", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Go", "last_name": "Hirai", "name": null }, { "creator_type": "author", "first_name": "Marie", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Koshino", "name": null }, { "creator_type": "author", "first_name": "Eri", "last_name": "Nishizawa", "name": null }, { "creator_type": "author", "first_name": "Kana", "last_name": "Oonuma", "name": null }, { "creator_type": "author", "first_name": "Eisuke", "last_name": "Ota", "name": null }, { "creator_type": "author", "first_name": "Toru", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Hashizume", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Tamura", "name": null }, { "creator_type": "author", "first_name": "Mitsuaki", "last_name": "Okada", "name": null }, { "creator_type": "author", "first_name": "Taeko", "last_name": "Miyagi", "name": null }, { "creator_type": "author", "first_name": "Mikiko", "last_name": "Sodeoka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/jacsau.0c00058" }, "pmcid": { "normalized": "PMC8395706" }, "pmid": { "normalized": "34467279" } }, "mesh": [], "publication": { "conference_name": null, "date": "2021 Feb 22", "date_precision": "day", "issue": "2", "normalized_date": "2021-02-22", "pages": "137-146", "proceedings_title": null, "publisher": "", "title": "JACS Au", "volume": "1", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Ganglioside GM3 Analogues Containing Monofluoromethylene-Linked Sialoside: Synthesis, Stereochemical Effects, Conformational Behavior, and Biological Activities.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "C. elegans spe-9 class genes encode sperm proteins with indispensable roles during fertilization. We have previously reported that spe-45 belongs to the spe-9 class, based on the finding that self-sperm of spe-45(tm3715) hermaphrodites were not consumed by fertilization. In this study, we directly observed live fertilization in the spermatheca of fem-1(hc17) females after mating with spe-45(tm3715) males. As expected, it was clearly shown that spe-45 mutant spermatozoa failed to fuse with the oocyte plasma membrane. Thus, our live imaging system for C. elegans fertilization seems to be useful for evaluation of the functions of male and female gametes.", "classifications": [ { "id": "Onami", "label": "Group Onami", "parent": "Fujiwara", "type": "group" }, { "id": "Fujiwara", "label": "Team Fujiwara", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Jun", "last_name": "Takayama", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Tajima", "name": null }, { "creator_type": "author", "first_name": "Shuichi", "last_name": "Onami", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Nishimura", "name": null } ], "identifiers": { "doi": { "normalized": "10.17912/micropub.biology.000372" }, "pmcid": { "normalized": "PMC7900825" }, "pmid": { "normalized": "33644705" } }, "mesh": [], "publication": { "conference_name": null, "date": "2021 Feb 21", "date_precision": "day", "issue": "", "normalized_date": "2021-02-21", "pages": "", "proceedings_title": null, "publisher": "", "title": "microPublication biology", "volume": "2021", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "C. elegans spermatozoa lacking spe-45 are incapable of fusing with the oocyte plasma membrane.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: Cisplatin (CDDP) significantly prolongs survival in various cancers, but many patients also develop resistance that results in treatment failure. Thus, this study aimed to elucidate the underlying mechanisms by which ovarian cancer cells acquire CDDP resistance. METHODS: We evaluated the metabolic profiles in CDDP-sensitive ovarian cancer A2780 cells and CDDP-resistant A2780cis cells using capillary electrophoresis-time-of-flight mass spectrometry (CE-TOFMS). We further examined the expression of glutamine metabolism enzymes using real-time PCR and Western blot analyses. Cell viability was accessed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. RESULTS: The results showed that levels of glutamine, glutamate, and glutathione (GSH), a key drug resistance mediator synthesized from glutamate, were significantly elevated in A2780cis cells than those in A2780 cells. Furthermore, glutamine starvation decreased the GSH levels and CDDP resistance in A2780cis cells. Interestingly, the expression of glutamine synthetase (GS/GLUL), which synthesizes glutamine from glutamate and thereby negatively regulates GSH production, was almost completely suppressed in resistant A2780cis cells. In addition, treatment of A2780cis cells with 5-aza-2'-deoxycytidine, a DNA-demethylating agent, restored GS expression and reduced CDDP resistance. In contrast, GS knockdown in CDDP-sensitive A2780 cells induced CDDP resistance. CONCLUSIONS: The results indicate that upregulation of GSH synthesis from glutamine via DNA methylation-mediated silencing of GS causes CDDP resistance in A2780cis cells. Therefore, glutamine metabolism could be a novel therapeutic target against CDDP resistance.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Jing", "last_name": "Guo", "name": null }, { "creator_type": "author", "first_name": "Kiyotoshi", "last_name": "Satoh", "name": null }, { "creator_type": "author", "first_name": "Sho", "last_name": "Tabata", "name": null }, { "creator_type": "author", "first_name": "Masaru", "last_name": "Mori", "name": null }, { "creator_type": "author", "first_name": "Masaru", "last_name": "Tomita", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null } ], "identifiers": { "doi": { "normalized": "10.1186/s12885-021-07879-5" }, "pmcid": { "normalized": "PMC7891143" }, "pmid": { "normalized": "33596851" } }, "mesh": [ { "descriptor": "Antineoplastic Agents", "descriptor_ui": "D000970", "major_topic": false }, { "descriptor": "Apoptosis", "descriptor_ui": "D017209", "major_topic": false }, { "descriptor": "Cell Proliferation", "descriptor_ui": "D049109", "major_topic": false }, { "descriptor": "Cellular Reprogramming", "descriptor_ui": "D065150", "major_topic": false }, { "descriptor": "Cisplatin", "descriptor_ui": "D002945", "major_topic": false }, { "descriptor": "Drug Resistance, Neoplasm", "descriptor_ui": "D019008", "major_topic": true }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Gene Silencing", "descriptor_ui": "D020868", "major_topic": true }, { "descriptor": "Glutamate-Ammonia Ligase", "descriptor_ui": "D005974", "major_topic": false }, { "descriptor": "Glutamine", "descriptor_ui": "D005973", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Metabolome", "descriptor_ui": "D055442", "major_topic": true }, { "descriptor": "Ovarian Neoplasms", "descriptor_ui": "D010051", "major_topic": false }, { "descriptor": "Tumor Cells, Cultured", "descriptor_ui": "D014407", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Feb 17", "date_precision": "day", "issue": "1", "normalized_date": "2021-02-17", "pages": "174", "proceedings_title": null, "publisher": "", "title": "BMC cancer", "volume": "21", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Reprogramming of glutamine metabolism via glutamine synthetase silencing induces cisplatin resistance in A2780 ovarian cancer cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: Oocyte quality decreases with aging, thereby increasing errors in fertilization, chromosome segregation, and embryonic cleavage. Oocyte appearance also changes with aging, suggesting a functional relationship between oocyte quality and appearance. However, no methods are available to objectively quantify age-associated changes in oocyte appearance. RESULTS: We show that statistical image processing of Nomarski differential interference contrast microscopy images can be used to quantify age-associated changes in oocyte appearance in the nematode Caenorhabditis elegans. Max-min value (mean difference between the maximum and minimum intensities within each moving window) quantitatively characterized the difference in oocyte cytoplasmic texture between 1- and 3-day-old adults (Day 1 and Day 3 oocytes, respectively). With an appropriate parameter set, the gray level co-occurrence matrix (GLCM)-based texture feature Correlation (COR) more sensitively characterized this difference than the Max-min Value. Manipulating the smoothness of and/or adding irregular structures to the cytoplasmic texture of Day 1 oocyte images reproduced the difference in Max-min Value but not in COR between Day 1 and Day 3 oocytes. Increasing the size of granules in synthetic images recapitulated the age-associated changes in COR. Manual measurements validated that the cytoplasmic granules in oocytes become larger with aging. CONCLUSIONS: The Max-min value and COR objectively quantify age-related changes in C. elegans oocyte in Nomarski DIC microscopy images. Our methods provide new opportunities for understanding the mechanism underlying oocyte aging.", "classifications": [ { "id": "Onami", "label": "Group Onami", "parent": "Fujiwara", "type": "group" }, { "id": "Fujiwara", "label": "Team Fujiwara", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Momoko", "last_name": "Imakubo", "name": null }, { "creator_type": "author", "first_name": "Jun", "last_name": "Takayama", "name": null }, { "creator_type": "author", "first_name": "Hatsumi", "last_name": "Okada", "name": null }, { "creator_type": "author", "first_name": "Shuichi", "last_name": "Onami", "name": null } ], "identifiers": { "doi": { "normalized": "10.1186/s12859-021-03990-3" }, "pmcid": { "normalized": "PMC7890843" }, "pmid": { "normalized": "33596821" } }, "mesh": [ { "descriptor": "Aging", "descriptor_ui": "D000375", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Caenorhabditis elegans", "descriptor_ui": "D017173", "major_topic": true }, { "descriptor": "Caenorhabditis elegans Proteins", "descriptor_ui": "D029742", "major_topic": false }, { "descriptor": "Chromosome Segregation", "descriptor_ui": "D020090", "major_topic": false }, { "descriptor": "Oocytes", "descriptor_ui": "D009865", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Feb 17", "date_precision": "day", "issue": "1", "normalized_date": "2021-02-17", "pages": "73", "proceedings_title": null, "publisher": "", "title": "BMC bioinformatics", "volume": "22", "year": 2021 }, "ssbd": { "database": [], "repository": [ "ssbd-repos-000158" ] }, "title": "Statistical image processing quantifies the changes in cytoplasmic texture associated with aging in Caenorhabditis elegans oocytes.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Linkage logic theory provides a mathematical criterion to control network dynamics by manipulating activities of a subset of network nodes, which are collectively called a feedback vertex set (FVS). Because many biological functions emerge from dynamics of biological networks, this theory provides a promising tool for controlling biological functions. By manipulating the activity of FVS molecules identified in a gene regulatory network (GRN) for fate specification of seven tissues in ascidian embryos, we previously succeeded in reproducing six of the seven cell types. Simultaneously, we discovered that the experimentally reconstituted GRN lacked information sufficient to reproduce muscle cells. Here, we utilized linkage logic theory as a tool to find missing edges in the GRN. Then, we identified a FVS from an updated version of the GRN and confirmed that manipulating the activity of this FVS was sufficient to induce all seven cell types, even in a multi-cellular environment. Thus, linkage logic theory provides tools to find missing edges in experimentally reconstituted networks, to determine whether reconstituted networks contain sufficient information to fulfil expected functions, and to reprogram cell fate.", "classifications": [ { "id": "Mochizuki", "label": "Group Mochizuki", "parent": "Eiraku", "type": "group" }, { "id": "Eiraku", "label": "Team Eiraku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Kenji", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Kazuki", "last_name": "Maeda", "name": null }, { "creator_type": "author", "first_name": "Miki", "last_name": "Tokuoka", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Mochizuki", "name": null }, { "creator_type": "author", "first_name": "Yutaka", "last_name": "Satou", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41598-021-83045-y" }, "pmcid": { "normalized": "PMC7889898" }, "pmid": { "normalized": "33597570" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Chordata", "descriptor_ui": "D043344", "major_topic": false }, { "descriptor": "Embryonic Development", "descriptor_ui": "D047108", "major_topic": false }, { "descriptor": "Gene Expression Regulation, Developmental", "descriptor_ui": "D018507", "major_topic": false }, { "descriptor": "Gene Regulatory Networks", "descriptor_ui": "D053263", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Models, Biological", "descriptor_ui": "D008954", "major_topic": true }, { "descriptor": "Muscle Cells", "descriptor_ui": "D032342", "major_topic": false }, { "descriptor": "Reproduction", "descriptor_ui": "D012098", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Systems Biology", "descriptor_ui": "D049490", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Feb 17", "date_precision": "day", "issue": "1", "normalized_date": "2021-02-17", "pages": "4001", "proceedings_title": null, "publisher": "", "title": "Scientific reports", "volume": "11", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Using linkage logic theory to control dynamics of a gene regulatory network of a chordate embryo.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Primordial germ cells (PGCs) are the founding population of the germ cell lineage that undergo a multistep process to generate spermatozoa or oocytes. Establishing an appropriate culture system for PGCs is a key challenge in reproductive biology. By a chemical screening using mouse PGC-like cells (mPGCLCs), which were induced from mouse embryonic stem cells, we reported previously that forskolin and rolipram synergistically enhanced the proliferation/survival of mPGCLCs with an average expansion rate of ~20-fold. In the present study, we evaluated other chemicals or cytokines to see whether they would improve the current mPGCLC culture system. Among the chemicals and cytokines examined, in the presence of forskolin and rolipram, cyclosporin A (CsA) and fibroblast growth factors (FGFs: FGF2 and FGF10) effectively enhanced the expansion of mPGCLCs in vitro (~50-fold on average). During the expansion by CsA or FGFs, mPGCLCs comprehensively erased their DNA methylation to acquire a profile equivalent to that of gonadal germ cells in vivo, while maintaining their highly motile phenotype as well as their transcriptional properties as sexually uncommitted PGCs. Importantly, these mPGCLCs robustly contributed to spermatogenesis and produced fertile offspring. Furthermore, mouse PGCs (mPGCs) cultured with CsA ex vivo showed transcriptomes and DNA methylomes similar to those of cultured mPGCLCs. The improved culture system for mPGCLCs/mPGCs would be instructive for addressing key questions in PGC biology, including the mechanisms for germ cell migration, epigenetic reprogramming, and sex determination of the germline.", "classifications": [ { "id": "Yamamoto", "label": "Group Yamamoto", "parent": "Toyoshima", "type": "group" }, { "id": "Toyoshima", "label": "Team Toyoshima", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Ohta", "name": null }, { "creator_type": "author", "first_name": "Yukihiro", "last_name": "Yabuta", "name": null }, { "creator_type": "author", "first_name": "Kazuki", "last_name": "Kurimoto", "name": null }, { "creator_type": "author", "first_name": "Tomonori", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Murase", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Mitinori", "last_name": "Saitou", "name": null } ], "identifiers": { "doi": { "normalized": "10.1093/biolre/ioaa195" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "33079185" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Apoptosis", "descriptor_ui": "D017209", "major_topic": false }, { "descriptor": "Cell Cycle", "descriptor_ui": "D002453", "major_topic": false }, { "descriptor": "Cell Proliferation", "descriptor_ui": "D049109", "major_topic": false }, { "descriptor": "Cell Survival", "descriptor_ui": "D002470", "major_topic": false }, { "descriptor": "Colforsin", "descriptor_ui": "D005576", "major_topic": false }, { "descriptor": "Cyclosporine", "descriptor_ui": "D016572", "major_topic": false }, { "descriptor": "Enzyme Inhibitors", "descriptor_ui": "D004791", "major_topic": false }, { "descriptor": "Fibroblast Growth Factor 10", "descriptor_ui": "D051526", "major_topic": false }, { "descriptor": "Fibroblast Growth Factor 2", "descriptor_ui": "D016222", "major_topic": false }, { "descriptor": "Germ Cells", "descriptor_ui": "D005854", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Rolitetracycline", "descriptor_ui": "D012382", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Whole Genome Sequencing", "descriptor_ui": "D000073336", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Feb 11", "date_precision": "day", "issue": "2", "normalized_date": "2021-02-11", "pages": "344-360", "proceedings_title": null, "publisher": "", "title": "Biology of reproduction", "volume": "104", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Cyclosporin A and FGF signaling support the proliferation/survival of mouse primordial germ cell-like cells in vitrodagger.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Post-translational methylation plays a crucial role in regulating and optimizing protein function. Protein histidine methylation, occurring as the two isomers 1- and 3-methylhistidine (1MH and 3MH), was first reported five decades ago, but remains largely unexplored. Here we report that METTL9 is a broad-specificity methyltransferase that mediates the formation of the majority of 1MH present in mouse and human proteomes. METTL9-catalyzed methylation requires a His-x-His (HxH) motif, where \"x\" is preferably a small amino acid, allowing METTL9 to methylate a number of HxH-containing proteins, including the immunomodulatory protein S100A9 and the NDUFB3 subunit of mitochondrial respiratory Complex I. Notably, METTL9-mediated methylation enhances respiration via Complex I, and the presence of 1MH in an HxH-containing peptide reduced its zinc binding affinity. Our results establish METTL9-mediated 1MH as a pervasive protein modification, thus setting the stage for further functional studies on protein histidine methylation.", "classifications": [ { "id": "Sodeoka", "label": "Group Sodeoka", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Erna", "last_name": "Davydova", "name": null }, { "creator_type": "author", "first_name": "Tadahiro", "last_name": "Shimazu", "name": null }, { "creator_type": "author", "first_name": "Maren Kirstin", "last_name": "Schuhmacher", "name": null }, { "creator_type": "author", "first_name": "Magnus E.", "last_name": "Jakobsson", "name": null }, { "creator_type": "author", "first_name": "Hanneke L. D. M.", "last_name": "Willemen", "name": null }, { "creator_type": "author", "first_name": "Tongri", "last_name": "Liu", "name": null }, { "creator_type": "author", "first_name": "Anders", "last_name": "Moen", "name": null }, { "creator_type": "author", "first_name": "Angela Y. Y.", "last_name": "Ho", "name": null }, { "creator_type": "author", "first_name": "Jedrzej", "last_name": "Malecki", "name": null }, { "creator_type": "author", "first_name": "Lisa", "last_name": "Schroer", "name": null }, { "creator_type": "author", "first_name": "Rita", "last_name": "Pinto", "name": null }, { "creator_type": "author", "first_name": "Takehiro", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Ida A.", "last_name": "Gronsberg", "name": null }, { "creator_type": "author", "first_name": "Yoshihiro", "last_name": "Sohtome", "name": null }, { "creator_type": "author", "first_name": "Mai", "last_name": "Akakabe", "name": null }, { "creator_type": "author", "first_name": "Sara", "last_name": "Weirich", "name": null }, { "creator_type": "author", "first_name": "Masaki", "last_name": "Kikuchi", "name": null }, { "creator_type": "author", "first_name": "Jesper V.", "last_name": "Olsen", "name": null }, { "creator_type": "author", "first_name": "Naoshi", "last_name": "Dohmae", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Umehara", "name": null }, { "creator_type": "author", "first_name": "Mikiko", "last_name": "Sodeoka", "name": null }, { "creator_type": "author", "first_name": "Valentina", "last_name": "Siino", "name": null }, { "creator_type": "author", "first_name": "Michael A.", "last_name": "McDonough", "name": null }, { "creator_type": "author", "first_name": "Niels", "last_name": "Eijkelkamp", "name": null }, { "creator_type": "author", "first_name": "Christopher J.", "last_name": "Schofield", "name": null }, { "creator_type": "author", "first_name": "Albert", "last_name": "Jeltsch", "name": null }, { "creator_type": "author", "first_name": "Yoichi", "last_name": "Shinkai", "name": null }, { "creator_type": "author", "first_name": "Pal O.", "last_name": "Falnes", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41467-020-20670-7" }, "pmcid": { "normalized": "PMC7873184" }, "pmid": { "normalized": "33563959" } }, "mesh": [ { "descriptor": "Amino Acid Motifs", "descriptor_ui": "D020816", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Histidine", "descriptor_ui": "D006639", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mammals", "descriptor_ui": "D008322", "major_topic": false }, { "descriptor": "Methylation", "descriptor_ui": "D008745", "major_topic": false }, { "descriptor": "Methylhistidines", "descriptor_ui": "D008762", "major_topic": false }, { "descriptor": "Methyltransferases", "descriptor_ui": "D008780", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Mitochondria", "descriptor_ui": "D008928", "major_topic": false }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": false }, { "descriptor": "Protein Processing, Post-Translational", "descriptor_ui": "D011499", "major_topic": false }, { "descriptor": "Proteome", "descriptor_ui": "D020543", "major_topic": false }, { "descriptor": "Substrate Specificity", "descriptor_ui": "D013379", "major_topic": false }, { "descriptor": "Zinc", "descriptor_ui": "D015032", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Feb 9", "date_precision": "day", "issue": "1", "normalized_date": "2021-02-09", "pages": "891", "proceedings_title": null, "publisher": "", "title": "Nature communications", "volume": "12", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "The methyltransferase METTL9 mediates pervasive 1-methylhistidine modification in mammalian proteomes.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Gravity determines shape of body tissue and affects the functions of life, both in plants and animals. The cellular response to gravity is an active process of mechanotransduction. Although plants and animals share some common mechanisms of gravity sensing in spite of their distant phylogenetic origin, each species has its own mechanism to sense and respond to gravity. In this review, we discuss current understanding regarding the mechanisms of cellular gravity sensing in plants and animals. Understanding gravisensing also contributes to life on Earth, e.g., understanding osteoporosis and muscle atrophy. Furthermore, in the current age of Mars exploration, understanding cellular responses to gravity will form the foundation of living in space.", "classifications": [ { "id": "Sawano", "label": "Group Sawano", "parent": "Shintaku", "type": "group" }, { "id": "Shintaku", "label": "Team Shintaku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Ken", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Hideyuki", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Furuichi", "name": null }, { "creator_type": "author", "first_name": "Masatsugu", "last_name": "Toyota", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Furutani-Seiki", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Haruko", "last_name": "Watanabe-Takano", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Shinohara", "name": null }, { "creator_type": "author", "first_name": "Takuro", "last_name": "Numaga-Tomita", "name": null }, { "creator_type": "author", "first_name": "Asako", "last_name": "Sakaue-Sawano", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Miyawaki", "name": null }, { "creator_type": "author", "first_name": "Keiji", "last_name": "Naruse", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41526-020-00130-8" }, "pmcid": { "normalized": "PMC7870899" }, "pmid": { "normalized": "33558517" } }, "mesh": [], "publication": { "conference_name": null, "date": "2021 Feb 8", "date_precision": "day", "issue": "1", "normalized_date": "2021-02-08", "pages": "2", "proceedings_title": null, "publisher": "", "title": "NPJ microgravity", "volume": "7", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Gravity sensing in plant and animal cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Reduction of elastin in the skin causes various skin diseases as well as wrinkles and sagging with aging. Sialidase is a hydrolase that cleaves a sialic acid residue from sialoglycoconjugate. Cleavage of sialic acid from microfibrils by the sialidase isozyme Neu1 facilitates elastic fiber assembly. In the present study, we showed that a lower layer of the dermis and muscle showed relatively intense sialidase activity. The sialidase activity in the skin decreased with aging. Choline and geranate (CAGE), one of the ionic liquids, can deliver the sialidase subcutaneously while maintaining the enzymatic activity. The elastin level in the dermis was increased by applying sialidase from Arthrobacter ureafaciens (AUSA) with CAGE on the skin for 5 days in rats and senescence-accelerated mice prone 1 and 8. Sialidase activity in the dermis was considered to be mainly due to Neu2 based on the expression level of sialidase isozyme mRNA. Transdermal administration of Neu2 with CAGE also increased the level of elastin in the dermis. Therefore, not only Neu1 but also Neu2 would be involved in elastic fiber assembly. Transdermal administration of sialidase is expected to be useful for improvement of wrinkles and skin disorders due to the loss of elastic fibers.", "classifications": [ { "id": "Suzuki", "label": "Group Suzuki", "parent": "Takekawa", "type": "group" }, { "id": "Takekawa", "label": "Team Takekawa", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Akira", "last_name": "Minami", "name": null }, { "creator_type": "author", "first_name": "Yuka", "last_name": "Fujita", "name": null }, { "creator_type": "author", "first_name": "Jun", "last_name": "Goto", "name": null }, { "creator_type": "author", "first_name": "Ayano", "last_name": "Iuchi", "name": null }, { "creator_type": "author", "first_name": "Kosei", "last_name": "Fujita", "name": null }, { "creator_type": "author", "first_name": "Yasuyo", "last_name": "Mikami", "name": null }, { "creator_type": "author", "first_name": "Mako", "last_name": "Shiratori", "name": null }, { "creator_type": "author", "first_name": "Ami", "last_name": "Ishii", "name": null }, { "creator_type": "author", "first_name": "Samir", "last_name": "Mitragotri", "name": null }, { "creator_type": "author", "first_name": "Yasunori", "last_name": "Iwao", "name": null }, { "creator_type": "author", "first_name": "Hiroaki", "last_name": "Kanazawa", "name": null }, { "creator_type": "author", "first_name": "Yuuki", "last_name": "Kurebayashi", "name": null }, { "creator_type": "author", "first_name": "Tadanobu", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Tadamune", "last_name": "Otsubo", "name": null }, { "creator_type": "author", "first_name": "Kiyoshi", "last_name": "Ikeda", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Suzuki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41598-021-82820-1" }, "pmcid": { "normalized": "PMC7870814" }, "pmid": { "normalized": "33558588" } }, "mesh": [ { "descriptor": "Administration, Cutaneous", "descriptor_ui": "D000279", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Dermis", "descriptor_ui": "D020405", "major_topic": false }, { "descriptor": "Elastin", "descriptor_ui": "D004549", "major_topic": false }, { "descriptor": "Isoenzymes", "descriptor_ui": "D007527", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Neuraminidase", "descriptor_ui": "D009439", "major_topic": true }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Rats, Wistar", "descriptor_ui": "D017208", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Feb 8", "date_precision": "day", "issue": "1", "normalized_date": "2021-02-08", "pages": "3302", "proceedings_title": null, "publisher": "", "title": "Scientific reports", "volume": "11", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Enhancement of elastin expression by transdermal administration of sialidase isozyme Neu2.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "A new method for the generation of tertiary radicals through single electron reduction of alkylsulfones promoted by Zn and 1,10-phenanthroline has been developed. These radicals could be employed in the Giese reaction, affording structurally diverse quaternary products in good yields. With the high modularity and functional group compatibility of sulfones, the utility of this method was demonstrated by intramolecular and iterative reactions to give complex structures. The radical generation process was investigated by control experiments and theoretical calculations.", "classifications": [ { "id": "Nanbo", "label": "Group Nanbo", "parent": "Tsuchiya", "type": "group" }, { "id": "Tsuchiya", "label": "Team Tsuchiya", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Masakazu", "last_name": "Nambo", "name": null }, { "creator_type": "author", "first_name": "Yasuyo", "last_name": "Tahara", "name": null }, { "creator_type": "author", "first_name": "Jacky C.-H.", "last_name": "Yim", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Yokogawa", "name": null }, { "creator_type": "author", "first_name": "Cathleen M.", "last_name": "Crudden", "name": null } ], "identifiers": { "doi": { "normalized": "10.1039/d1sc00133g" }, "pmcid": { "normalized": "PMC8179647" }, "pmid": { "normalized": "34168761" } }, "mesh": [], "publication": { "conference_name": null, "date": "2021 Feb 4", "date_precision": "day", "issue": "13", "normalized_date": "2021-02-04", "pages": "4866-4871", "proceedings_title": null, "publisher": "", "title": "Chemical science", "volume": "12", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Synthesis of quaternary centres by single electron reduction and alkylation of alkylsulfones.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "In this study, Morimoto et al. sought to investigate how reactive oxygen species (ROS) are regulated in spermatogonial stem cells (SSCs). Using in vivo and genomic approaches, the authors report that hypoxic niche sets the ROS levels in SSCs, and spermatogenesis depends on an intricate balance between NOX1 and mitochondria-derived ROS.", "classifications": [ { "id": "Yamamoto", "label": "Group Yamamoto", "parent": "Toyoshima", "type": "group" }, { "id": "Toyoshima", "label": "Team Toyoshima", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Hiroko", "last_name": "Morimoto", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Takehiro", "last_name": "Miyazaki", "name": null }, { "creator_type": "author", "first_name": "Narumi", "last_name": "Ogonuki", "name": null }, { "creator_type": "author", "first_name": "Atsuo", "last_name": "Ogura", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Mito", "last_name": "Kanatsu-Shinohara", "name": null }, { "creator_type": "author", "first_name": "Chihiro", "last_name": "Yabe-Nishimura", "name": null }, { "creator_type": "author", "first_name": "Hongliang", "last_name": "Zhang", "name": null }, { "creator_type": "author", "first_name": "Yves", "last_name": "Pommier", "name": null }, { "creator_type": "author", "first_name": "Andreas", "last_name": "Trumpp", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Shinohara", "name": null } ], "identifiers": { "doi": { "normalized": "10.1101/gad.339903.120" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "33446567" } }, "mesh": [ { "descriptor": "Adult Germline Stem Cells", "descriptor_ui": "D000072956", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Division", "descriptor_ui": "D002455", "major_topic": false }, { "descriptor": "Cell Hypoxia", "descriptor_ui": "D015687", "major_topic": false }, { "descriptor": "Cell Proliferation", "descriptor_ui": "D049109", "major_topic": false }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "DNA Topoisomerases, Type I", "descriptor_ui": "D004264", "major_topic": false }, { "descriptor": "Gene Expression Regulation, Developmental", "descriptor_ui": "D018507", "major_topic": false }, { "descriptor": "Hypoxia-Inducible Factor 1, alpha Subunit", "descriptor_ui": "D051795", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Mitochondria", "descriptor_ui": "D008928", "major_topic": false }, { "descriptor": "NADPH Oxidase 1", "descriptor_ui": "D000074624", "major_topic": false }, { "descriptor": "Oxygen", "descriptor_ui": "D010100", "major_topic": false }, { "descriptor": "Reactive Oxygen Species", "descriptor_ui": "D017382", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Feb 1", "date_precision": "day", "issue": "3-4", "normalized_date": "2021-02-01", "pages": "250-260", "proceedings_title": null, "publisher": "", "title": "Genes & Development", "volume": "35", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "An interplay of NOX1-derived ROS and oxygen determines the spermatogonial stem cell self-renewal efficiency under hypoxia.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Articular cartilage protects and lubricates joints for smooth motion and transmission of loads. Owing to its high water content, chondrocytes within the cartilage are exposed to high levels of hydrostatic pressure, which has been shown to promote chondrocyte identity through unknown mechanisms. Here, we investigate the effects of hydrostatic pressure on chondrocyte state and behavior, and discover that application of hydrostatic pressure promotes chondrocyte quiescence and prevents maturation towards the hypertrophic state. Mechanistically, hydrostatic pressure reduces the amount of trimethylated H3K9 (K3K9me3)-marked constitutive heterochromatin and concomitantly increases H3K27me3-marked facultative heterochromatin. Reduced levels of H3K9me3 attenuates expression of pre-hypertrophic genes, replication and transcription, thereby reducing replicative stress. Conversely, promoting replicative stress by inhibition of topoisomerase II decreases Sox9 expression, suggesting that it enhances chondrocyte maturation. Our results reveal how hydrostatic pressure triggers chromatin remodeling to impact cell fate and function.This article has an associated First Person interview with the first author of the paper.", "classifications": [ { "id": "Maki", "label": "Group Maki", "parent": "Toyoshima", "type": "group" }, { "id": "Toyoshima", "label": "Team Toyoshima", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Koichiro", "last_name": "Maki", "name": null }, { "creator_type": "author", "first_name": "Michele M.", "last_name": "Nava", "name": null }, { "creator_type": "author", "first_name": "Clémentine", "last_name": "Villeneuve", "name": null }, { "creator_type": "author", "first_name": "Minki", "last_name": "Chang", "name": null }, { "creator_type": "author", "first_name": "Katsuko S.", "last_name": "Furukawa", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Ushida", "name": null }, { "creator_type": "author", "first_name": "Sara A.", "last_name": "Wickström", "name": null } ], "identifiers": { "doi": { "normalized": "10.1242/jcs.247643" }, "pmcid": { "normalized": "PMC7860130" }, "pmid": { "normalized": "33310912" } }, "mesh": [ { "descriptor": "Cartilage, Articular", "descriptor_ui": "D002358", "major_topic": true }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Chondrocytes", "descriptor_ui": "D019902", "major_topic": true }, { "descriptor": "Heterochromatin", "descriptor_ui": "D006570", "major_topic": false }, { "descriptor": "Hydrostatic Pressure", "descriptor_ui": "D006874", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Jan 27", "date_precision": "day", "issue": "2", "normalized_date": "2021-01-27", "pages": "", "proceedings_title": null, "publisher": "", "title": "Journal of cell science", "volume": "134", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Hydrostatic pressure prevents chondrocyte differentiation through heterochromatin remodeling.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "We report herein experimental observations of the reciprocating motion of a self-propelled droplet floating on the surface of an aqueous surfactant solution and a simple reaction model capable of reproducing the observed behavior of the droplet. The reciprocating motion was observed in a quasi-one-dimensional annular channel, so the reciprocation was not caused by reflections at boundaries. To understand the reciprocation, our model assumes a reaction between the surface active substance emitted from the droplet and surfactants dissolved in the aqueous solution. This reaction invokes an inversion of the surface tension gradient and thus the droplet's reciprocation. We show that the model can reproduce experimental results semi-quantitatively using numerical simulations with realistic parameters.", "classifications": [ { "id": "Nagayama", "label": "Group Nagayama", "parent": "Fujiwara", "type": "group" }, { "id": "Fujiwara", "label": "Team Fujiwara", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Shinpei", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Nakata", "name": null }, { "creator_type": "author", "first_name": "Masaharu", "last_name": "Nagayama", "name": null } ], "identifiers": { "doi": { "normalized": "10.1039/d0sm01500h" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "33174574" } }, "mesh": [], "publication": { "conference_name": null, "date": "2021 Jan 22", "date_precision": "day", "issue": "2", "normalized_date": "2021-01-22", "pages": "388-396", "proceedings_title": null, "publisher": "", "title": "Soft matter", "volume": "17", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "A surfactant reaction model for the reciprocating motion of a self-propelled droplet.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Innate fear intimately connects to the life preservation in crises, although this relationships is not fully understood. Here, we report that presentation of a supernormal innate fear inducer 2-methyl-2-thiazoline (2MT), but not learned fear stimuli, induced robust systemic hypothermia/hypometabolism and suppressed aerobic metabolism via phosphorylation of pyruvate dehydrogenase, thereby enabling long-term survival in a lethal hypoxic environment. These responses exerted potent therapeutic effects in cutaneous and cerebral ischemia/reperfusion injury models. In contrast to hibernation, 2MT stimulation accelerated glucose uptake in the brain and suppressed oxygen saturation in the blood. Whole-brain mapping and chemogenetic activation revealed that the sensory representation of 2MT orchestrates physiological responses via brain stem Sp5/NST to midbrain PBN pathway. 2MT, as a supernormal stimulus of innate fear, induced exaggerated, latent life-protective effects in mice. If this system is preserved in humans, it may be utilized to give rise to a new field: \"sensory medicine.\"", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Tomohiko", "last_name": "Matsuo", "name": null }, { "creator_type": "author", "first_name": "Tomoko", "last_name": "Isosaka", "name": null }, { "creator_type": "author", "first_name": "Lijun", "last_name": "Tang", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Reiko", "last_name": "Kobayakawa", "name": null }, { "creator_type": "author", "first_name": "Ko", "last_name": "Kobayakawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s42003-020-01629-2" }, "pmcid": { "normalized": "PMC7822961" }, "pmid": { "normalized": "33483561" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Drug Evaluation, Preclinical", "descriptor_ui": "D004353", "major_topic": false }, { "descriptor": "Fear", "descriptor_ui": "D005239", "major_topic": false }, { "descriptor": "Hibernation", "descriptor_ui": "D006605", "major_topic": true }, { "descriptor": "Hypothermia, Induced", "descriptor_ui": "D007036", "major_topic": false }, { "descriptor": "Hypoxia", "descriptor_ui": "D000860", "major_topic": false }, { "descriptor": "Instinct", "descriptor_ui": "D007323", "major_topic": true }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Odorants", "descriptor_ui": "D009812", "major_topic": true }, { "descriptor": "Reperfusion Injury", "descriptor_ui": "D015427", "major_topic": false }, { "descriptor": "Thiazoles", "descriptor_ui": "D013844", "major_topic": true } ], "publication": { "conference_name": null, "date": "2021 Jan 22", "date_precision": "day", "issue": "1", "normalized_date": "2021-01-22", "pages": "101", "proceedings_title": null, "publisher": "", "title": "Communications biology", "volume": "4", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Artificial hibernation/life-protective state induced by thiazoline-related innate fear odors.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "CRISPR guide RNA libraries have been iteratively improved to provide increasingly efficient reagents, although their large size is a barrier for many applications. We design an optimised minimal genome-wide human CRISPR-Cas9 library (MinLibCas9) by mining existing large-scale gene loss-of-function datasets, resulting in a greater than 42% reduction in size compared to other CRISPR-Cas9 libraries while preserving assay sensitivity and specificity. MinLibCas9 provides backward compatibility with existing datasets, increases the dynamic range of CRISPR-Cas9 screens and extends their application to complex models and assays.", "classifications": [ { "id": "Yusa", "label": "Group Yusa", "parent": "Eiraku", "type": "group" }, { "id": "Eiraku", "label": "Team Eiraku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Emanuel", "last_name": "Goncalves", "name": null }, { "creator_type": "author", "first_name": "Mark", "last_name": "Thomas", "name": null }, { "creator_type": "author", "first_name": "Fiona M.", "last_name": "Behan", "name": null }, { "creator_type": "author", "first_name": "Gabriele", "last_name": "Picco", "name": null }, { "creator_type": "author", "first_name": "Clare", "last_name": "Pacini", "name": null }, { "creator_type": "author", "first_name": "Felicity", "last_name": "Allen", "name": null }, { "creator_type": "author", "first_name": "Alessandro", "last_name": "Vinceti", "name": null }, { "creator_type": "author", "first_name": "Mamta", "last_name": "Sharma", "name": null }, { "creator_type": "author", "first_name": "David A.", "last_name": "Jackson", "name": null }, { "creator_type": "author", "first_name": "Stacey", "last_name": "Price", "name": null }, { "creator_type": "author", "first_name": "Charlotte M.", "last_name": "Beaver", "name": null }, { "creator_type": "author", "first_name": "Oliver", "last_name": "Dovey", "name": null }, { "creator_type": "author", "first_name": "David", "last_name": "Parry-Smith", "name": null }, { "creator_type": "author", "first_name": "Francesco", "last_name": "Iorio", "name": null }, { "creator_type": "author", "first_name": "Leopold", "last_name": "Parts", "name": null }, { "creator_type": "author", "first_name": "Kosuke", "last_name": "Yusa", "name": null }, { "creator_type": "author", "first_name": "Mathew J.", "last_name": "Garnett", "name": null } ], "identifiers": { "doi": { "normalized": "10.1186/s13059-021-02268-4" }, "pmcid": { "normalized": "PMC7818936" }, "pmid": { "normalized": "33478580" } }, "mesh": [ { "descriptor": "CRISPR-Cas Systems", "descriptor_ui": "D064113", "major_topic": true }, { "descriptor": "Gene Library", "descriptor_ui": "D015723", "major_topic": false }, { "descriptor": "Genome, Human", "descriptor_ui": "D015894", "major_topic": true }, { "descriptor": "Genome-Wide Association Study", "descriptor_ui": "D055106", "major_topic": false }, { "descriptor": "Genomic Library", "descriptor_ui": "D015698", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Organoids", "descriptor_ui": "D009940", "major_topic": false }, { "descriptor": "RNA, Guide, CRISPR-Cas Systems", "descriptor_ui": "D000094704", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Jan 21", "date_precision": "day", "issue": "1", "normalized_date": "2021-01-21", "pages": "40", "proceedings_title": null, "publisher": "", "title": "Genome biology", "volume": "22", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Minimal genome-wide human CRISPR-Cas9 library.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Post-operative endophthalmitis caused by Enterococcus spp. progresses rapidly and often results in substantial and irreversible vision loss. Therefore, novel alternative treatments that are effective against enterococcal endophthalmitis are required. Bacteriophage therapy has the potential to be an optional therapy for infectious diseases. Therefore, we investigated the therapeutic potential of three newly isolated enterococcal phages, phiEF7H, phiEF14H1, and phiEF19G, in E. faecalis-induced endophthalmitis. These phages could lyse the broad-range E. faecalis, including strains derived from endophthalmitis and vancomycin-resistant E. faecalis in vitro, as determined by the streak test. Morphological and genomic analyses revealed that these phages were classified into the Herelleviridae genus Kochikohdavirus. The whole genomes of these phages contained 143,399, 143,280, and 143,400 bp, respectively. Endophthalmitis was induced in mice by injection of three strains of E. faecalis derived from post-operative endophthalmitis or vancomycin-resistant strains into the vitreous body. The number of viable bacteria and infiltration of neutrophils in the eye were both decreased by intravitreous injection of phiEF7H, phiEF14H1, and phiEF19G 6 h after injection of all E. faecalis strains. Thus, these results suggest that these newly isolated phages may serve as promising candidates for phage therapy against endophthalmitis.", "classifications": [ { "id": "Suzuki", "label": "Group Suzuki", "parent": "Takekawa", "type": "group" }, { "id": "Takekawa", "label": "Team Takekawa", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Azuki", "last_name": "Mizutani", "name": null }, { "creator_type": "author", "first_name": "Cheng", "last_name": "Tan", "name": null }, { "creator_type": "author", "first_name": "Yuji", "last_name": "Sugita", "name": null }, { "creator_type": "author", "first_name": "Shoji", "last_name": "Takada", "name": null }, { "creator_type": "author", "first_name": "Tatsuma", "last_name": "Kishimoto", "name": null }, { "creator_type": "author", "first_name": "Waka", "last_name": "Ishida", "name": null }, { "creator_type": "author", "first_name": "Tadahiro", "last_name": "Nasukawa", "name": null }, { "creator_type": "author", "first_name": "Takako", "last_name": "Ujihara", "name": null }, { "creator_type": "author", "first_name": "Isana", "last_name": "Nakajima", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Jumpei", "last_name": "Uchiyama", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Todokoro", "name": null }, { "creator_type": "author", "first_name": "Masanori", "last_name": "Daibata", "name": null }, { "creator_type": "author", "first_name": "Atsuki", "last_name": "Fukushima", "name": null }, { "creator_type": "author", "first_name": "Shigenobu", "last_name": "Matsuzaki", "name": null }, { "creator_type": "author", "first_name": "Ken", "last_name": "Fukuda", "name": null } ], "identifiers": { "doi": { "normalized": "10.3390/microorganisms9020212" }, "pmcid": { "normalized": "PMC7909552" }, "pmid": { "normalized": "33498561" } }, "mesh": [], "publication": { "conference_name": null, "date": "2021 Jan 20", "date_precision": "day", "issue": "2", "normalized_date": "2021-01-20", "pages": "e1011321", "proceedings_title": null, "publisher": "", "title": "Microorganisms", "volume": "9", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "In Vitro and In Vivo Evaluation of Three Newly Isolated Bacteriophage Candidates, phiEF7H, phiEF14H1, phiEF19G, for Treatment of Enterococcus faecalis Endophthalmitis.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Intervention studies have shown that n-3 polyunsaturated fatty acid (PUFA) supplementation is effective for the treatment of meibomian gland dysfunction (MGD). Ointment containing an analog of vitamin D has also been found to improve symptoms and signs of MGD. We have now evaluated the relation of MGD prevalence to dietary intake of fatty acids (FAs) and vitamin D among a Japanese population. Subjects comprised 300 adults aged 20 to 92 years residing on Takushima Island. MGD was diagnosed on the basis of subjective symptoms, lid margin abnormalities, and meibomian gland obstruction. Dietary FA and vitamin D intake was estimated with a brief-type self-administered diet history questionnaire. MGD prevalence was 35.3%. Multivariate adjusted odds ratios (95% confidence intervals) between extreme quintiles of intake for MGD prevalence were 0.40 (0.16-0.97) for total fat, 0.40 (0.17-0.97) for saturated FAs, 0.40 (0.17-0.97) for oleic acid, 0.52 (0.23-1.18) for n-3 PUFAs, 0.63 (0.27-1.49) for n-6 PUFAs, 1.32 (0.59-2.95) for the n-6/n-3 PUFA ratio, and 0.38 (0.17-0.87) for vitamin D. Total fat, saturated FA, oleic acid, and vitamin D intake may thus be negatively associated with MGD prevalence in the Japanese.", "classifications": [ { "id": "Suzuki", "label": "Group Suzuki", "parent": "Takekawa", "type": "group" }, { "id": "Takekawa", "label": "Team Takekawa", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Shima", "last_name": "Fukuoka", "name": null }, { "creator_type": "author", "first_name": "Reiko", "last_name": "Arita", "name": null }, { "creator_type": "author", "first_name": "Takanori", "last_name": "Mizoguchi", "name": null }, { "creator_type": "author", "first_name": "Motoko", "last_name": "Kawashima", "name": null }, { "creator_type": "author", "first_name": "Shizuka", "last_name": "Koh", "name": null }, { "creator_type": "author", "first_name": "Rika", "last_name": "Shirakawa", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Sasaki", "name": null }, { "creator_type": "author", "first_name": "Naoyuki", "last_name": "Morishige", "name": null } ], "identifiers": { "doi": { "normalized": "10.3390/jcm10020350" }, "pmcid": { "normalized": "PMC7831319" }, "pmid": { "normalized": "33477594" } }, "mesh": [], "publication": { "conference_name": null, "date": "2021 Jan 18", "date_precision": "day", "issue": "2", "normalized_date": "2021-01-18", "pages": "350", "proceedings_title": null, "publisher": "", "title": "Journal of clinical medicine", "volume": "10", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Relation of Dietary Fatty Acids and Vitamin D to the Prevalence of Meibomian Gland Dysfunction in Japanese Adults: The Hirado-Takushima Study.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Flocculation has been recognized for hundreds of years as an important phenomenon in brewing and wastewater treatment. However, the underlying molecular mechanisms remain elusive. The lack of a distinct phenotype to differentiate between slow-growing mutants and floc-forming mutants prevents the isolation of floc-related gene by conventional mutant screening. To overcome this, we performed a two-step Escherichia coli mutant screen. The initial screen of E. coli for mutants conferring floc production during high salt treatment yielded a mutant containing point mutations in 61 genes. The following screen of the corresponding single-gene mutants identified two genes, mrcB, encoding a peptidoglycan-synthesizing enzyme and cpxA, encoding a histidine kinase of a two-component signal transduction system that contributed to salt tolerance and flocculation prevention. Both single mutants formed flocs during high salt shock, these flocs contained cytosolic proteins. DeltacpxA exhibited decreased growth with increasing floc production and addition of magnesium to DeltacpxA suppressed floc production effectively. In contrast, the growth of DeltamrcB was inconsistent under high salt conditions. In both strains, flocculation was accompanied by the release of membrane vesicles containing inner and outer membrane proteins. Of 25 histidine kinase mutants tested, DeltacpxA produced the highest amount of proteins in floc. Expression of cpxP was up-regulated by high salt in DeltacpxA, suggesting that high salinity and activation of CpxR might promote floc formation. The finding that DeltamrcB or DeltacpxA conferred floc production indicates that cell envelope stress triggered by unfavorable environmental conditions cause the initiation of flocculation in E. coli.", "classifications": [ { "id": "Akaike", "label": "Group Akaike", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Keita", "last_name": "Sugawara", "name": null }, { "creator_type": "author", "first_name": "Hayato", "last_name": "Toyoda", "name": null }, { "creator_type": "author", "first_name": "Mami", "last_name": "Kimura", "name": null }, { "creator_type": "author", "first_name": "Shunsuke", "last_name": "Hayasaka", "name": null }, { "creator_type": "author", "first_name": "Hiromi", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Kunio", "last_name": "Ihara", "name": null }, { "creator_type": "author", "first_name": "Tomoaki", "last_name": "Ida", "name": null }, { "creator_type": "author", "first_name": "Takaaki", "last_name": "Akaike", "name": null }, { "creator_type": "author", "first_name": "Eiji", "last_name": "Ando", "name": null }, { "creator_type": "author", "first_name": "Mamoru", "last_name": "Hyodo", "name": null }, { "creator_type": "author", "first_name": "Yoshihiro", "last_name": "Hayakawa", "name": null }, { "creator_type": "author", "first_name": "Shin", "last_name": "Hamamoto", "name": null }, { "creator_type": "author", "first_name": "Nobuyuki", "last_name": "Uozumi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1042/bcj20200723" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "33196080" } }, "mesh": [ { "descriptor": "Bacterial Proteins", "descriptor_ui": "D001426", "major_topic": false }, { "descriptor": "Cell Membrane", "descriptor_ui": "D002462", "major_topic": false }, { "descriptor": "Cell Wall", "descriptor_ui": "D002473", "major_topic": false }, { "descriptor": "Cytosol", "descriptor_ui": "D003600", "major_topic": false }, { "descriptor": "Escherichia coli", "descriptor_ui": "D004926", "major_topic": false }, { "descriptor": "Escherichia coli Proteins", "descriptor_ui": "D029968", "major_topic": false }, { "descriptor": "Flocculation", "descriptor_ui": "D005427", "major_topic": false }, { "descriptor": "Membrane Proteins", "descriptor_ui": "D008565", "major_topic": false }, { "descriptor": "Penicillin-Binding Proteins", "descriptor_ui": "D046915", "major_topic": false }, { "descriptor": "Peptidoglycan Glycosyltransferase", "descriptor_ui": "D046928", "major_topic": false }, { "descriptor": "Point Mutation", "descriptor_ui": "D017354", "major_topic": false }, { "descriptor": "Protein Kinases", "descriptor_ui": "D011494", "major_topic": false }, { "descriptor": "Salt Tolerance", "descriptor_ui": "D055049", "major_topic": false }, { "descriptor": "Serine-Type D-Ala-D-Ala Carboxypeptidase", "descriptor_ui": "D046929", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Jan 15", "date_precision": "day", "issue": "1", "normalized_date": "2021-01-15", "pages": "41-59", "proceedings_title": null, "publisher": "", "title": "The Biochemical journal", "volume": "478", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Loss of cell wall integrity genes cpxA and mrcB causes flocculation in Escherichia coli.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "", "classifications": [ { "id": "Sodeoka", "label": "Group Sodeoka", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Makoto", "last_name": "Yoritate", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Morita", "name": null }, { "creator_type": "author", "first_name": "Manuel", "last_name": "Gemander", "name": null }, { "creator_type": "author", "first_name": "Masaki", "last_name": "Morita", "name": null }, { "creator_type": "author", "first_name": "Tomohiro", "last_name": "Yamashita", "name": null }, { "creator_type": "author", "first_name": "Mikiko", "last_name": "Sodeoka", "name": null }, { "creator_type": "author", "first_name": "Go", "last_name": "Hirai", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/acs.orglett.0c04135" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "33370526" } }, "mesh": [], "publication": { "conference_name": null, "date": "2021 Jan 15", "date_precision": "day", "issue": "2", "normalized_date": "2021-01-15", "pages": "624", "proceedings_title": null, "publisher": "", "title": "Organic letters", "volume": "23", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Correction to \"Synthesis of DFGH-Ring Derivatives of Physalins via One-Pot Construction of GH-Ring and Evaluation of Their NF-kappaB-Inhibitory Activity\".", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Viral cell-to-cell spread, a method employed by several viral families for entrance via cell junctions, is highly relevant to the pathogenesis of various viral infections. Cell-to-cell spread of herpes simplex virus 1 (HSV-1) is known to depend greatly on envelope glycoprotein E (gE). However, the molecular mechanism by which gE acts in HSV-1 cell-to-cell spread and the mechanisms of cell-to-cell spread by other herpesviruses remain poorly understood. Here, we describe our identification of prohibitin-1 as a novel gE-interacting host cell protein. Ectopic expression of prohibitin-1 increased gE-dependent HSV-1 cell-to-cell spread. As observed with the gE-null mutation, decreased expression or pharmacological inhibition of prohibitin-1 reduced HSV-1 cell-to-cell spread without affecting the yield of virus progeny. Similar effects were produced by pharmacological inhibition of the mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) pathway, wherein prohibitin-1 acts as a protein scaffold and is required for induction of this pathway. Furthermore, artificial activation of the MAPK/ERK pathway restored HSV-1 cell-to-cell spread impaired by the gE-null mutation. Notably, pharmacological inhibition of prohibitins or the MAPK/ERK pathway reduced viral cell-to-cell spread of representative members in all herpesvirus subfamilies. Our results suggest that prohibitin-1 contributes to gE-dependent HSV-1 cell-to-cell spread via the MAPK/ERK pathway and that this mechanism is conserved throughout the Herpesviridae, whereas gE is conserved only in the Alphaherpesvirinae subfamily.IMPORTANCE Herpesviruses are ubiquitous pathogens of various animals, including humans. These viruses primarily pass through cell junctions to spread to uninfected cells. This method of cell-to-cell spread is an important pathogenic characteristic of these viruses. Here, we show that the host cell protein prohibitin-1 contributes to HSV-1 cell-to-cell spread via a downstream intracellular signaling cascade, the MAPK/ERK pathway. We also demonstrate that the role of the prohibitin-1-mediated MAPK/ERK pathway in viral cell-to-cell spread is conserved in representative members of every herpesvirus subfamily. This study has revealed a common molecular mechanism of the cell-to-cell spread of herpesviruses.", "classifications": [ { "id": "Takekawa", "label": "Group Takekawa", "parent": "Takekawa", "type": "group" }, { "id": "Takekawa", "label": "Team Takekawa", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Mizuki", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Jun", "last_name": "Arii", "name": null }, { "creator_type": "author", "first_name": "Kosuke", "last_name": "Takeshima", "name": null }, { "creator_type": "author", "first_name": "Ayano", "last_name": "Fukui", "name": null }, { "creator_type": "author", "first_name": "Masayuki", "last_name": "Shimojima", "name": null }, { "creator_type": "author", "first_name": "Hiroko", "last_name": "Kozuka-Hata", "name": null }, { "creator_type": "author", "first_name": "Masaaki", "last_name": "Oyama", "name": null }, { "creator_type": "author", "first_name": "Takeharu", "last_name": "Minamitani", "name": null }, { "creator_type": "author", "first_name": "Teruhito", "last_name": "Yasui", "name": null }, { "creator_type": "author", "first_name": "Yuji", "last_name": "Kubota", "name": null }, { "creator_type": "author", "first_name": "Mutsuhiro", "last_name": "Takekawa", "name": null }, { "creator_type": "author", "first_name": "Isao", "last_name": "Kosugi", "name": null }, { "creator_type": "author", "first_name": "Yuhei", "last_name": "Maruzuru", "name": null }, { "creator_type": "author", "first_name": "Naoto", "last_name": "Koyanagi", "name": null }, { "creator_type": "author", "first_name": "Akihisa", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Yasuko", "last_name": "Mori", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Kawaguchi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1128/jvi.01413-20" }, "pmcid": { "normalized": "PMC7925112" }, "pmid": { "normalized": "33177205" } }, "mesh": [ { "descriptor": "A549 Cells", "descriptor_ui": "D000072283", "major_topic": false }, { "descriptor": "Cell Communication", "descriptor_ui": "D002450", "major_topic": true }, { "descriptor": "Extracellular Signal-Regulated MAP Kinases", "descriptor_ui": "D048049", "major_topic": false }, { "descriptor": "Herpes Simplex", "descriptor_ui": "D006561", "major_topic": false }, { "descriptor": "Herpesvirus 1, Human", "descriptor_ui": "D018259", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Intercellular Junctions", "descriptor_ui": "D007365", "major_topic": false }, { "descriptor": "Mitogen-Activated Protein Kinases", "descriptor_ui": "D020928", "major_topic": false }, { "descriptor": "Prohibitins", "descriptor_ui": "D000091402", "major_topic": false }, { "descriptor": "Repressor Proteins", "descriptor_ui": "D012097", "major_topic": false }, { "descriptor": "Viral Envelope Proteins", "descriptor_ui": "D014759", "major_topic": false }, { "descriptor": "Virus Replication", "descriptor_ui": "D014779", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Jan 13", "date_precision": "day", "issue": "3", "normalized_date": "2021-01-13", "pages": "e01413-20", "proceedings_title": null, "publisher": "", "title": "Journal of virology", "volume": "95", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Prohibitin-1 Contributes to Cell-to-Cell Transmission of Herpes Simplex Virus 1 via the MAPK/ERK Signaling Pathway.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "(18)F-FDG PET/CT has been used as an indicator of chemotherapy effects, but cancer cells can remain even when no FDG uptake is detected, indicating the importance of exploring other metabolomic pathways. Therefore, we explored the amino acid metabolism, including L-type amino acid transporter-1 (LAT1), in breast cancer tissues and clarified the role of LAT1 in therapeutic resistance and clinical outcomes of patients. We evaluated LAT1 expression before and after neoadjuvant chemotherapy and examined the correlation of glucose uptake using FDG-PET with the pathological response of patients. It revealed that LAT1 levels correlated with proliferation after chemotherapy, and amino acid and glucose metabolism were closely correlated. In addition, LAT1 was considered to be involved in treatment resistance and sensitivity only in luminal type breast cancer. Results of in vitro analyses revealed that LAT1 promoted amino acid uptake, which contributed to energy production by supplying amino acids to the TCA cycle. However, in MCF-7 cells treated with chemotherapeutic agents, oncometabolites and branched-chain amino acids also played a pivotal role in energy production and drug resistance, despite decreased glucose metabolism. In conclusion, LAT1 was involved in drug resistance and could be a novel therapeutic target against chemotherapy resistance in luminal type breast cancer.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Suzuki", "label": "Group Suzuki", "parent": "Takekawa", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" }, { "id": "Takekawa", "label": "Team Takekawa", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Miku", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Narumi", "last_name": "Harada-Shoji", "name": null }, { "creator_type": "author", "first_name": "Takafumi", "last_name": "Toyohara", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Masatoshi", "last_name": "Itoh", "name": null }, { "creator_type": "author", "first_name": "Minoru", "last_name": "Miyashita", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Tada", "name": null }, { "creator_type": "author", "first_name": "Masakazu", "last_name": "Amari", "name": null }, { "creator_type": "author", "first_name": "Naohiko", "last_name": "Anzai", "name": null }, { "creator_type": "author", "first_name": "Shozo", "last_name": "Furumoto", "name": null }, { "creator_type": "author", "first_name": "Takaaki", "last_name": "Abe", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Takanori", "last_name": "Ishida", "name": null }, { "creator_type": "author", "first_name": "Hironobu", "last_name": "Sasano", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41598-020-80668-5" }, "pmcid": { "normalized": "PMC7803739" }, "pmid": { "normalized": "33436954" } }, "mesh": [ { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Amino Acids", "descriptor_ui": "D000596", "major_topic": false }, { "descriptor": "Breast Neoplasms", "descriptor_ui": "D001943", "major_topic": false }, { "descriptor": "Cell Proliferation", "descriptor_ui": "D049109", "major_topic": false }, { "descriptor": "Drug Resistance, Neoplasm", "descriptor_ui": "D019008", "major_topic": false }, { "descriptor": "Energy Metabolism", "descriptor_ui": "D004734", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Gene Expression", "descriptor_ui": "D015870", "major_topic": true }, { "descriptor": "Glucose", "descriptor_ui": "D005947", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Large Neutral Amino Acid-Transporter 1", "descriptor_ui": "D027283", "major_topic": false }, { "descriptor": "MCF-7 Cells", "descriptor_ui": "D061986", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Neoadjuvant Therapy", "descriptor_ui": "D020360", "major_topic": false }, { "descriptor": "Positron Emission Tomography Computed Tomography", "descriptor_ui": "D000072078", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Jan 12", "date_precision": "day", "issue": "1", "normalized_date": "2021-01-12", "pages": "589", "proceedings_title": null, "publisher": "", "title": "Scientific reports", "volume": "11", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "L-type amino acid transporter 1 is associated with chemoresistance in breast cancer via the promotion of amino acid metabolism.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The Human Genome Project, completed in 2003 by an international consortium, is considered one of the most important achievements for mankind in the 21st century [...].", "classifications": [ { "id": "Hamamoto", "label": "Group Hamamoto", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Ryuji", "last_name": "Hamamoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.3390/biom11010090" }, "pmcid": { "normalized": "PMC7828229" }, "pmid": { "normalized": "33445802" } }, "mesh": [ { "descriptor": "Artificial Intelligence", "descriptor_ui": "D001185", "major_topic": true }, { "descriptor": "Biomedical Research", "descriptor_ui": "D035843", "major_topic": true }, { "descriptor": "Genomics", "descriptor_ui": "D023281", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Image Processing, Computer-Assisted", "descriptor_ui": "D007091", "major_topic": false }, { "descriptor": "Natural Language Processing", "descriptor_ui": "D009323", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Jan 12", "date_precision": "day", "issue": "1", "normalized_date": "2021-01-12", "pages": "", "proceedings_title": null, "publisher": "", "title": "Biomolecules", "volume": "11", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Application of Artificial Intelligence for Medical Research.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Spindle assembly is spatially regulated by a chromosome-derived Ran- GTP gradient. Previous work proposed that Ran-GTP activates spindle assembly factors (SAFs) around chromosomes by dissociating inhibitory importins from SAFs. However, it is unclear whether the Ran-GTP gradient equivalently activates SAFs that localize at distinct spindle regions. In addition, Ran's dual functions in interphase nucleocytoplasmic transport and mitotic spindle assembly have made it difficult to assess its mitotic roles in somatic cells. Here, using auxin-inducible degron technology in human cells, we developed acute mitotic depletion assays to dissect Ran's mitotic roles systematically and separately from its interphase function. In contrast to the prevailing model, we found that the Ran pathway is not essential for spindle assembly activities that occur at sites spatially separated from chromosomes, including activating NuMA for spindle-pole focusing or for targeting TPX2. On the other hand, Ran-GTP is required to localize HURP and HSET specifically at chromosome-proximal regions to set proper spindle length during prometaphase. We demonstrated that Ran-GTP and importin-beta coordinately promote HURP's dynamic microtubule binding-dissociation cycle, which maintains HURP near chromosomes during metaphase. Together, we propose that the Ran pathway acts on spindle assembly independently of its interphase functions in mitotic human cells but does not equivalently regulate all Ran-regulated SAFs. Ran-dependent spindle assembly is likely coupled with additional parallel pathways that activate SAFs distantly located from the chromosomes.", "classifications": [ { "id": "Sato", "label": "Group Sato", "parent": "Tsuchiya", "type": "group" }, { "id": "Tsuchiya", "label": "Team Tsuchiya", "type": "team" } ], "creators": [ { "creator_type": "contributor", "first_name": "Kenta", "last_name": "Tsuchiya", "name": null }, { "creator_type": "contributor", "first_name": "Hisato", "last_name": "Hayashi", "name": null }, { "creator_type": "contributor", "first_name": "Momoko", "last_name": "Nishina", "name": null }, { "creator_type": "contributor", "first_name": "Masako", "last_name": "Okumura", "name": null }, { "creator_type": "contributor", "first_name": "Yoshikatsu", "last_name": "Sato", "name": null }, { "creator_type": "contributor", "first_name": "Masato T.", "last_name": "Kanemaki", "name": null }, { "creator_type": "contributor", "first_name": "Gohta", "last_name": "Goshima", "name": null }, { "creator_type": "contributor", "first_name": "Tomomi", "last_name": "Kiyomitsu", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.cub.2020.09.091" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "33186548" } }, "mesh": [ { "descriptor": "Cell Cycle Proteins", "descriptor_ui": "D018797", "major_topic": false }, { "descriptor": "Chromosomes", "descriptor_ui": "D002875", "major_topic": false }, { "descriptor": "Gene Knock-In Techniques", "descriptor_ui": "D055879", "major_topic": false }, { "descriptor": "Guanine Nucleotide Exchange Factors", "descriptor_ui": "D020662", "major_topic": false }, { "descriptor": "Guanosine Triphosphate", "descriptor_ui": "D006160", "major_topic": false }, { "descriptor": "HCT116 Cells", "descriptor_ui": "D045325", "major_topic": false }, { "descriptor": "HEK293 Cells", "descriptor_ui": "D057809", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Intravital Microscopy", "descriptor_ui": "D000069416", "major_topic": false }, { "descriptor": "Kinesins", "descriptor_ui": "D016547", "major_topic": false }, { "descriptor": "Microtubule-Associated Proteins", "descriptor_ui": "D008869", "major_topic": false }, { "descriptor": "Mitosis", "descriptor_ui": "D008938", "major_topic": true }, { "descriptor": "Neoplasm Proteins", "descriptor_ui": "D009363", "major_topic": false }, { "descriptor": "Nuclear Proteins", "descriptor_ui": "D009687", "major_topic": false }, { "descriptor": "ran GTP-Binding Protein", "descriptor_ui": "D020931", "major_topic": false }, { "descriptor": "Spindle Poles", "descriptor_ui": "D064047", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Jan 11", "date_precision": "day", "issue": "1", "normalized_date": "2021-01-11", "pages": "115-127.e3", "proceedings_title": null, "publisher": "", "title": "", "volume": "31", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Ran-GTP Is Non-essential to Activate NuMA for Mitotic Spindle-Pole Focusing but Dynamically Polarizes HURP Near Chromosomes.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "We demonstrate hyperspectral imaging by visible-wavelength two-photon excitation microscopy using line illumination and slit-confocal detection. A femtosecond pulsed laser light at 530 nm was used for the simultaneous excitation of fluorescent proteins with different emission wavelengths. The use of line illumination enabled efficient detection of hyperspectral images and achieved simultaneous detection of three fluorescence spectra in the observation of living HeLa cells with an exposure time of 1 ms per line, which is equivalent to about 2 micros per pixel in point scanning, with 160 data points per spectrum. On combining linear spectral unmixing techniques, localization of fluorescent probes in the cells was achieved. A theoretical investigation of the imaging property revealed high-depth discrimination property attained through the combination of nonlinear excitation and slit detection.", "classifications": [ { "id": "Fujita", "label": "Group Fujita", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Toshiki", "last_name": "Kubo", "name": null }, { "creator_type": "author", "first_name": "Kenta", "last_name": "Temma", "name": null }, { "creator_type": "author", "first_name": "Nicholas I.", "last_name": "Smith", "name": null }, { "creator_type": "author", "first_name": "Kai", "last_name": "Lu", "name": null }, { "creator_type": "author", "first_name": "Tomoki", "last_name": "Matsuda", "name": null }, { "creator_type": "author", "first_name": "Takeharu", "last_name": "Nagai", "name": null }, { "creator_type": "author", "first_name": "Katsumasa", "last_name": "Fujita", "name": null } ], "identifiers": { "doi": { "normalized": "10.1364/ol.413526" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "33362007" } }, "mesh": [], "publication": { "conference_name": null, "date": "2021 Jan 1", "date_precision": "day", "issue": "1", "normalized_date": "2021-01-01", "pages": "37-40", "proceedings_title": null, "publisher": "", "title": "Optics letters", "volume": "46", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Hyperspectral two-photon excitation microscopy using visible wavelength.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "During cotyledon growth, the pavement cells, which make up most of the epidermal layer, undergo dynamic morphological changes from simple to jigsaw puzzle-like shapes in most dicotyledonous plants. Morphological analysis of cell shapes generally involves the segmentation of cells from input images followed by the extraction of shape descriptors that can be used to assess cell shape. Traditionally, replica and fluorescent labeling methods have been used for time-lapse observation of cotyledon epidermal cell morphogenesis, but these methods require expensive microscopes and can be technically demanding. Here, we propose a silver-nano-ink coating method for time-lapse imaging and quantification of morphological changes in the epidermal cells of growing Arabidopsis thaliana cotyledons. To obtain high-resolution and wide-area cotyledon surface images, we placed the seedlings on a biaxial goniometer and adjusted the cotyledons, which were coated by dropping silver ink onto them, to be as horizontal to the focal plane as possible. The omnifocal images that had the most epidermal cell shapes in the observation area were taken at multiple points to cover the whole surface area of the cotyledon. The multi-point omnifocal images were automatically stitched, and the epidermal cells were automatically and accurately segmented by machine learning. Quantification of cell morphological features based on the segmented images demonstrated that the proposed method could quantitatively evaluate jigsaw puzzle-shaped cell growth and morphogenesis. The method was successfully applied to phenotyping of the bpp125 triple mutant, which has defective pavement cell morphogenesis. The proposed method will be useful for time-lapse non-destructive phenotyping of plant surface structures and is easier to use than the conversional methods that require fluorescent dye labeling or transformation with marker gene constructs and expensive microscopes such as the confocal laser microscope.", "classifications": [ { "id": "Higaki", "label": "Group Higaki", "parent": "Ueda", "type": "group" }, { "id": "Ueda", "label": "Team Ueda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Kotomi", "last_name": "Kikukawa", "name": null }, { "creator_type": "author", "first_name": "Kazuki", "last_name": "Yoshimura", "name": null }, { "creator_type": "author", "first_name": "Akira", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Takumi", "last_name": "Higaki", "name": null } ], "identifiers": { "doi": { "normalized": "10.3389/fpls.2021.745980" }, "pmcid": { "normalized": "PMC8490765" }, "pmid": { "normalized": "34621288" } }, "mesh": [], "publication": { "conference_name": null, "date": "2021", "date_precision": "year", "issue": "", "normalized_date": "2021", "pages": "745980", "proceedings_title": null, "publisher": "", "title": "Frontiers in plant science", "volume": "12", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Metal-Nano-Ink Coating for Monitoring and Quantification of Cotyledon Epidermal Cell Morphogenesis.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "RNA sequencing profiles and characterizes cell and tissue samples, giving important insights into molecular mechanisms. Such data is imperative for cardiomyocytes derived from induced pluripotent stem cells (iPSC-CMs) and used in related translational and basic research. Here we provide reliable protocols to extract differentially expressed genes in iPSC-CMs with RNA sequencing.", "classifications": [ { "id": "Yamamoto", "label": "Group Yamamoto", "parent": "Toyoshima", "type": "group" }, { "id": "Toyoshima", "label": "Team Toyoshima", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Chikako", "last_name": "Okubo", "name": null }, { "creator_type": "author", "first_name": "Megumi", "last_name": "Narita", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Yoshinori", "last_name": "Yoshida", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/978-1-0716-1484-6_19" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "34302660" } }, "mesh": [ { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Chromosome Mapping", "descriptor_ui": "D002874", "major_topic": false }, { "descriptor": "Gene Expression Profiling", "descriptor_ui": "D020869", "major_topic": false }, { "descriptor": "Gene Library", "descriptor_ui": "D015723", "major_topic": false }, { "descriptor": "Genes, Reporter", "descriptor_ui": "D017930", "major_topic": false }, { "descriptor": "Genome, Human", "descriptor_ui": "D015894", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Induced Pluripotent Stem Cells", "descriptor_ui": "D057026", "major_topic": false }, { "descriptor": "MicroRNAs", "descriptor_ui": "D035683", "major_topic": false }, { "descriptor": "Myocytes, Cardiac", "descriptor_ui": "D032383", "major_topic": false }, { "descriptor": "Principal Component Analysis", "descriptor_ui": "D025341", "major_topic": false }, { "descriptor": "RNA", "descriptor_ui": "D012313", "major_topic": false }, { "descriptor": "RNA-Seq", "descriptor_ui": "D000081246", "major_topic": false }, { "descriptor": "Sequence Alignment", "descriptor_ui": "D016415", "major_topic": false }, { "descriptor": "Software", "descriptor_ui": "D012984", "major_topic": false }, { "descriptor": "Transcriptome", "descriptor_ui": "D059467", "major_topic": true } ], "publication": { "conference_name": null, "date": "2021", "date_precision": "year", "issue": "", "normalized_date": "2021", "pages": "193-217", "proceedings_title": null, "publisher": "", "title": "Methods in molecular biology (Clifton, N.J.)", "volume": "2320", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "RNA-Sequencing Analysis of Differentially Expressed Genes in Human iPSC-Derived Cardiomyocytes.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Parasitic root-knot nematodes transform the host's vascular cells into permanent feeding giant cells (GCs) to withdraw nutrients from the host plants. GCs are multinucleated metabolically active cells with distinctive cell wall structures; however, the genetic regulation of GC formation is largely unknown. In this study, the functions of the Arabidopsis thaliana transcription factor PUCHI during GC development were investigated. PUCHI expression was shown to be induced in early developing galls, suggesting the importance of the PUCHI gene in gall formation. Despite the puchi mutant not differing significantly from the wild type in nematode invasion and reproduction rates, puchi GC cell walls appeared to be thicker and lobate when compared to the wild type, while the cell membrane sometimes formed invaginations. In three-dimensional (3D) reconstructions of puchi GCs, they appeared to be more irregularly shaped than those in the wild type, with noticeable cell-surface protrusions and folds. Interestingly, the loss-of-function mutant of 3-KETOACYL-COA SYNTHASE 1 showed GC morphology and cell wall defects similar to those of the puchi mutant, suggesting that PUCHI may regulate GC development via very long chain fatty acid synthesis.", "classifications": [ { "id": "Higaki", "label": "Group Higaki", "parent": "Ueda", "type": "group" }, { "id": "Ueda", "label": "Team Ueda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Reira", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Mizuki", "last_name": "Yamada", "name": null }, { "creator_type": "author", "first_name": "Takumi", "last_name": "Higaki", "name": null }, { "creator_type": "author", "first_name": "Mitsuhiro", "last_name": "Aida", "name": null }, { "creator_type": "author", "first_name": "Minoru", "last_name": "Kubo", "name": null }, { "creator_type": "author", "first_name": "Allen Yi-Lun", "last_name": "Tsai", "name": null }, { "creator_type": "author", "first_name": "Shinichiro", "last_name": "Sawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.3389/fpls.2021.755610" }, "pmcid": { "normalized": "PMC8527015" }, "pmid": { "normalized": "34691131" } }, "mesh": [], "publication": { "conference_name": null, "date": "2021", "date_precision": "year", "issue": "", "normalized_date": "2021", "pages": "755610", "proceedings_title": null, "publisher": "", "title": "Frontiers in plant science", "volume": "12", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "PUCHI Regulates Giant Cell Morphology During Root-Knot Nematode Infection in Arabidopsis thaliana.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Non-alcoholic steatohepatitis (NASH) is a disease that has progressed from non-alcoholic fatty liver disease (NAFLD) and is characterized by inflammation and fibrosis. Two transient receptor potential canonical (TRPC) subfamily members, TRPC3 and TRPC6 (TRPC3/6), reportedly participate in the development of fibrosis in cardiovascular and renal systems. We hypothesized that TRPC3/6 may also participate in NASH fibrosis. We evaluated the effects of TRPC3 or TRPC6 functional deficiency in a NASH mouse model using choline-deficient, L-amino acid-defined, high-fat diet (CDAHFD). Wild-type (WT) and TRPC3 or TRPC6 gene-deficient (KO) mice were fed with CDAHFD or standard diet for 6 weeks. The CDAHFD-induced body weight loss in TRPC6 KO mice was significantly lower compared with WT mice with CDAHFD. CDAHFD treatment significantly increased TRPC3 mRNA expression level and tissue weight in WT liver, which were suppressed in TRPC3 KO mice. However, either systemic deletion of TRPC3 or TRPC6 failed to attenuate liver steatosis, inflammation and fibrosis. These results imply that TRPC3 and TRPC6 are unlikely to be involved in liver dysfunction and fibrosis of NASH model mice.", "classifications": [ { "id": "Nishida", "label": "Group Nishida", "parent": "Nishida", "type": "group" }, { "id": "Nishimura", "label": "Group Nishimura", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Kazuhiro", "last_name": "Nishiyama", "name": null }, { "creator_type": "author", "first_name": "Chiemi", "last_name": "Toyama", "name": null }, { "creator_type": "author", "first_name": "Yuri", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Tomohiro", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Akiyuki", "last_name": "Nishimura", "name": null }, { "creator_type": "author", "first_name": "Ryu", "last_name": "Nagata", "name": null }, { "creator_type": "author", "first_name": "Yasuo", "last_name": "Mori", "name": null }, { "creator_type": "author", "first_name": "Motohiro", "last_name": "Nishida", "name": null } ], "identifiers": { "doi": { "normalized": "10.1248/bpb.b20-00903" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "33642551" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Chemokine CCL2", "descriptor_ui": "D018932", "major_topic": false }, { "descriptor": "Choline Deficiency", "descriptor_ui": "D002796", "major_topic": false }, { "descriptor": "Diet, High-Fat", "descriptor_ui": "D059305", "major_topic": false }, { "descriptor": "Inflammation", "descriptor_ui": "D007249", "major_topic": false }, { "descriptor": "Liver", "descriptor_ui": "D008099", "major_topic": false }, { "descriptor": "Liver Cirrhosis", "descriptor_ui": "D008103", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Non-alcoholic Fatty Liver Disease", "descriptor_ui": "D065626", "major_topic": false }, { "descriptor": "TRPC Cation Channels", "descriptor_ui": "D050052", "major_topic": false }, { "descriptor": "TRPC6 Cation Channel", "descriptor_ui": "D000074287", "major_topic": false }, { "descriptor": "Tumor Necrosis Factor-alpha", "descriptor_ui": "D014409", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021", "date_precision": "year", "issue": "3", "normalized_date": "2021", "pages": "431-436", "proceedings_title": null, "publisher": "", "title": "Biological & pharmaceutical bulletin", "volume": "44", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Deletion of TRPC3 or TRPC6 Fails to Attenuate the Formation of Inflammation and Fibrosis in Non-alcoholic Steatohepatitis.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Deep learning is a promising method for medical image analysis because it can automatically acquire meaningful representations from raw data. However, a technical challenge lies in the difficulty of determining which types of internal representation are associated with a specific task, because feature vectors can vary dynamically according to individual inputs. Here, based on the magnetic resonance imaging (MRI) of gliomas, we propose a novel method to extract a shareable set of feature vectors that encode various parts in tumor imaging phenotypes. By applying vector quantization to latent representations, features extracted by an encoder are replaced with a fixed set of feature vectors. Hence, the set of feature vectors can be used in downstream tasks as imaging markers, which we call deep radiomics. Using deep radiomics, a classifier is established using logistic regression to predict the glioma grade with 90% accuracy. We also devise an algorithm to visualize the image region encoded by each feature vector, and demonstrate that the classification model preferentially relies on feature vectors associated with the presence or absence of contrast enhancement in tumor regions. Our proposal provides a data-driven approach to enhance the understanding of the imaging appearance of gliomas.", "classifications": [ { "id": "Hamamoto", "label": "Group Hamamoto", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Kazuma", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Mototaka", "last_name": "Miyake", "name": null }, { "creator_type": "author", "first_name": "Masamichi", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Ryuji", "last_name": "Hamamoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41598-021-90555-2" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "34035410" } }, "mesh": [ { "descriptor": "Algorithms", "descriptor_ui": "D000465", "major_topic": false }, { "descriptor": "Brain Neoplasms", "descriptor_ui": "D001932", "major_topic": false }, { "descriptor": "Glioma", "descriptor_ui": "D005910", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Image Processing, Computer-Assisted", "descriptor_ui": "D007091", "major_topic": false }, { "descriptor": "Magnetic Resonance Imaging", "descriptor_ui": "D008279", "major_topic": false }, { "descriptor": "Neoplasm Grading", "descriptor_ui": "D060787", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021", "date_precision": "year", "issue": "", "normalized_date": "2021", "pages": "", "proceedings_title": null, "publisher": "", "title": "Scientific Reports", "volume": "11", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Observing deep radiomics for the classification of glioma grades.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Bing-Neel syndrome (BNS), which presents with a variety of neurological complications, is a rare manifestation of the lymphoplasmacytic lymphoma (LPL) and is characterized by the infiltration of LPL cells into the central nervous system. In this study, we report the case of a patient with BNS, which was confirmed by detecting MYD88 L265P mutation in the cerebrospinal fluid (CSF) cells. A 74-year-old patient was diagnosed with IgG-variant LPL. He achieved a very good partial response to the treatment with rituximab and bendamustine (RB) and was stable for over 5 years, when presenting a slowly progressive motor deficit in the lower limbs. It was difficult to confirm BNS from morphological analysis of the CSF cells. After detecting MYD88 L265P mutation in the CSF cells, he was subsequently diagnosed with BNS and treated with RB and intrathecal chemotherapy, resulting in rapid clinical improvement. With the onset of neurological manifestation during the clinical course of LPL, the detection of MYD88 L265P mutation in the CSF cells could be helpful for the diagnosis and management of BNS.", "classifications": [ { "id": "Nishikii", "label": "Group Nishikii", "parent": "Shintaku", "type": "group" }, { "id": "Shintaku", "label": "Team Shintaku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yumiko", "last_name": "Maruyama", "name": null }, { "creator_type": "author", "first_name": "Hidekazu", "last_name": "Nishikii", "name": null }, { "creator_type": "author", "first_name": "Ryota", "last_name": "Matsuoka", "name": null }, { "creator_type": "author", "first_name": "Kenichi", "last_name": "Makishima", "name": null }, { "creator_type": "author", "first_name": "Naoki", "last_name": "Kurita", "name": null }, { "creator_type": "author", "first_name": "Manabu", "last_name": "Kusakabe", "name": null }, { "creator_type": "author", "first_name": "Yasuhisa", "last_name": "Yokoyama", "name": null }, { "creator_type": "author", "first_name": "Takayasu", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Mamiko", "last_name": "Sakata-Yanagimoto", "name": null }, { "creator_type": "author", "first_name": "Naoshi", "last_name": "Obara", "name": null }, { "creator_type": "author", "first_name": "Naoya", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Shigeru", "last_name": "Chiba", "name": null } ], "identifiers": { "doi": { "normalized": "10.11406/rinketsu.62.1493" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "34732622" } }, "mesh": [ { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Immunoglobulin G", "descriptor_ui": "D007074", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": false }, { "descriptor": "Myeloid Differentiation Factor 88", "descriptor_ui": "D053594", "major_topic": true }, { "descriptor": "Rituximab", "descriptor_ui": "D000069283", "major_topic": false }, { "descriptor": "Waldenstrom Macroglobulinemia", "descriptor_ui": "D008258", "major_topic": true } ], "publication": { "conference_name": null, "date": "2021", "date_precision": "year", "issue": "10", "normalized_date": "2021", "pages": "1493-1498", "proceedings_title": null, "publisher": "", "title": "[Rinsho ketsueki] The Japanese journal of clinical hematology", "volume": "62", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "[IgG-variant Bing-Neel syndrome diagnosed by detecting MYD88 L265P mutation in the cerebrospinal fluid cells].", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Over the last decade, tissue-clearing techniques have expanded the scale of volumetric fluorescence imaging of the brain, allowing for the comprehensive analysis of neuronal circuits at a millimeter scale. Multicolor imaging is particularly powerful for circuit tracing with fluorescence microscopy. However, multicolor imaging of large samples often suffers from chromatic aberration, where different excitation wavelengths of light have different focal points. In this study, we evaluated chromatic aberrations for representative objective lenses and a clearing agent with confocal microscopy and found that axial aberration is particularly problematic. Moreover, the axial chromatic aberrations were often depth-dependent. Therefore, we developed a program that is able to align depths for different fluorescence channels based on reference samples with fluorescent beads or data from guide stars within biological samples. We showed that this correction program can successfully correct chromatic aberrations found in confocal images of multicolor-labeled brain tissues. Our simple post hoc correction strategy is useful to obtain large-scale multicolor images of cleared tissues with minimal chromatic aberrations.", "classifications": [ { "id": "JPMJCR2021", "label": "JPMJCR2021", "researcher": "Hideki Enomoto", "type": "grant" }, { "id": "Enomoto", "label": "Group Enomoto", "parent": "Enomoto", "type": "group" }, { "id": "Imai", "label": "Group Imai", "parent": "Enomoto", "type": "group" }, { "id": "Enomoto", "label": "Team Enomoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Marcus N.", "last_name": "Leiwe", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Fujimoto", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Imai", "name": null } ], "identifiers": { "doi": { "normalized": "10.3389/fnana.2021.760063" }, "pmcid": { "normalized": "PMC8703134" }, "pmid": { "normalized": "34955764" } }, "mesh": [], "publication": { "conference_name": null, "date": "2021", "date_precision": "year", "issue": "", "normalized_date": "2021", "pages": "760063", "proceedings_title": null, "publisher": "", "title": "Frontiers in neuroanatomy", "volume": "15", "year": 2021 }, "ssbd": { "database": [], "repository": [ "ssbd-repos-000208" ] }, "title": "Post hoc Correction of Chromatic Aberrations in Large-Scale Volumetric Images in Confocal Microscopy.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Introduction: Physical distancing under the coronavirus disease 2019 (COVID-19) pandemic had a significant impact on lifestyles, including exercise routines. In this study, we examined the relationship between mental health and addictive behaviors, such as excessive exercise and the use of image and performance enhancing drugs (IPEDs) across 12 sport disciplines. Materials and methods: A large cross-sectional sample of the adult population (N = 2,295) was surveyed. The mean age was 33.09 (SD = 11.40). The number of male participants was 668 (30.0%). The use of IPEDs was assessed in conjunction with psychometric measures such as the Exercise Addiction Inventory (EAI) and the Appearance Anxiety Inventory (AAI). The participants were grouped into activity group (AG) and non-activity group (NAG) according to the presence or absence of their exercise habits. The results were compared between these groups, as well as across sport disciplines, while taking into account the relationship between different psychological measures and IPEDs consumption. Results: The frequency of IPEDs use was higher among AG (34.6%) than NAG (14.6%), although AG participants reported less history of addictions (7.1%) than NAG (11.8%). The logistic regression analysis revealed that scores equal to or above cutoff points, in both the EAI and AAI, predicted the IPEDs use. Regarding the differences across the various sport disciplines, those who were involved in practicing Weight Lifting and Cross Fit were found to be more at risk of excessive exercising and more inclined to use a wide range of IPEDs. Conclusions: Although exercise could help to increase well-being and prevent addictions during the COVID-19 pandemic, our results show that those in the AG are particularly vulnerable to excessive IPEDs use. Sport disciplines associated with higher EAI and AAI scores have also shown a higher tendency to excessive IPEDs use. Furthermore, the factor of having above the cutoff scores in EAI or AAI in each sport could indicate larger IPEDs consumption regardless of the discipline. In light of the current findings, it is necessary to better define the \"non-excessive\" levels of exercise in various sport disciplines and an adequate intake of IPEDs to ensure the safety and well-being of people during a pandemic.", "classifications": [ { "id": "Fujiwara", "label": "Group Fujiwara", "parent": "Fujiwara", "type": "group" }, { "id": "Fujiwara", "label": "Team Fujiwara", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Mami", "last_name": "Shibata", "name": null }, { "creator_type": "author", "first_name": "Julius", "last_name": "Burkauskas", "name": null }, { "creator_type": "author", "first_name": "Artemisa R.", "last_name": "Dores", "name": null }, { "creator_type": "author", "first_name": "Kei", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Sayaka", "last_name": "Yoshimura", "name": null }, { "creator_type": "author", "first_name": "Pierluigi", "last_name": "Simonato", "name": null }, { "creator_type": "author", "first_name": "Ilaria", "last_name": "De Luca", "name": null }, { "creator_type": "author", "first_name": "Dorotea", "last_name": "Cicconcelli", "name": null }, { "creator_type": "author", "first_name": "Valentina", "last_name": "Giorgetti", "name": null }, { "creator_type": "author", "first_name": "Irene P.", "last_name": "Carvalho", "name": null }, { "creator_type": "author", "first_name": "Fernando", "last_name": "Barbosa", "name": null }, { "creator_type": "author", "first_name": "Cristina", "last_name": "Monteiro", "name": null }, { "creator_type": "author", "first_name": "Toshiya", "last_name": "Murai", "name": null }, { "creator_type": "author", "first_name": "Maria A.", "last_name": "Gomez-Martinez", "name": null }, { "creator_type": "author", "first_name": "Zsolt", "last_name": "Demetrovics", "name": null }, { "creator_type": "author", "first_name": "Krisztina Edina", "last_name": "Abel", "name": null }, { "creator_type": "author", "first_name": "Attila", "last_name": "Szabo", "name": null }, { "creator_type": "author", "first_name": "Alejandra Rebeca Melero", "last_name": "Ventola", "name": null }, { "creator_type": "author", "first_name": "Eva Maria", "last_name": "Arroyo-Anllo", "name": null }, { "creator_type": "author", "first_name": "Ricardo M.", "last_name": "Santos-Labrador", "name": null }, { "creator_type": "author", "first_name": "Inga", "last_name": "Griskova-Bulanova", "name": null }, { "creator_type": "author", "first_name": "Aiste", "last_name": "Pranckeviciene", "name": null }, { "creator_type": "author", "first_name": "Giuseppe", "last_name": "Bersani", "name": null }, { "creator_type": "author", "first_name": "Hironobu", "last_name": "Fujiwara", "name": null }, { "creator_type": "author", "first_name": "Ornella", "last_name": "Corazza", "name": null } ], "identifiers": { "doi": { "normalized": "10.3389/fpsyg.2021.689058" }, "pmcid": { "normalized": "PMC8290335" }, "pmid": { "normalized": "34295291" } }, "mesh": [], "publication": { "conference_name": null, "date": "2021", "date_precision": "year", "issue": "", "normalized_date": "2021", "pages": "689058", "proceedings_title": null, "publisher": "", "title": "Frontiers in psychology", "volume": "12", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Exploring the Relationship Between Mental Well-Being, Exercise Routines, and the Intake of Image and Performance Enhancing Drugs During the Coronavirus Disease 2019 Pandemic: A Comparison Across Sport Disciplines.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Purpose: Patients with advanced/relapsed rare cancers have few treatment options. Analysis of circulating tumor DNA in plasma may identify actionable genomic biomarkers using a non-invasive approach. Patients and Methods: Rare cancer patients underwent prospective plasma-based NGS testing. Tissue NGS to test concordance was also conducted. Plasma DNA alterations were assessed for incidence, functional impact, therapeutic implications, correlation to survival, and comparison with tissue NGS. Results: Ninety-eight patients were analyzed. Diseases included soft-tissue sarcoma, ovarian carcinoma, and others. Mean turn-around-time for results was 9.5 days. Seventy-six patients had detectable gene alterations in plasma, with a median of 2.8 alterations/patient. Sixty patients had a likely pathogenic alteration. Five received matched-therapy based on plasma NGS results. Two developed known resistance mutations while on targeted therapy. Patients with an alteration having VAF ≥5% had a significantly shorter survival compared to those of lower VAF. Tissue NGS results from eleven of 22 patients showed complete or partial concordance with plasma NGS. Conclusion: Plasma NGS testing is less invasive and capable of identifying alterations in advanced rare cancers in a clinically meaningful timeframe. It should be further studied as a prospective enrollment assay in interventional studies for patients with rare advanced stage cancers. Clinical Registration: [https://www.umin.ac.jp/ctr/index-j.htm], identifier UMIN000034394.", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Hitomi Sumiyoshi", "last_name": "Okuma", "name": null }, { "creator_type": "author", "first_name": "Kan", "last_name": "Yonemori", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Kojima", "name": null }, { "creator_type": "author", "first_name": "Maki", "last_name": "Tanioka", "name": null }, { "creator_type": "author", "first_name": "Kazuki", "last_name": "Sudo", "name": null }, { "creator_type": "author", "first_name": "Emi", "last_name": "Noguchi", "name": null }, { "creator_type": "author", "first_name": "Susumu", "last_name": "Hijioka", "name": null }, { "creator_type": "author", "first_name": "Keiko", "last_name": "Wakakuwa", "name": null }, { "creator_type": "author", "first_name": "Ken", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Akihiro", "last_name": "Hirakawa", "name": null }, { "creator_type": "author", "first_name": "Aya", "last_name": "Kuchiba", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Kubo", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Ichikawa", "name": null }, { "creator_type": "author", "first_name": "Akihiko", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null }, { "creator_type": "author", "first_name": "Kenichi", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Mano", "name": null }, { "creator_type": "author", "first_name": "Noboru", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Yasuhiro", "last_name": "Fujiwara", "name": null } ], "identifiers": { "doi": { "normalized": "10.3389/fonc.2021.732525" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "34900683" } }, "mesh": [], "publication": { "conference_name": null, "date": "2021", "date_precision": "year", "issue": "", "normalized_date": "2021", "pages": "", "proceedings_title": null, "publisher": "", "title": "Frontiers in Oncology", "volume": "11", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Clinical Utility of Circulating Tumor DNA in Advanced Rare Cancers.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Introduction: Little is known about the impact of restrictive measures during the COVID-19 pandemic on self-image and engagement in exercise and other coping strategies alongside the use of image and performance-enhancing drugs (IPEDs) to boost performance and appearance. Objectives: To assess the role of anxiety about appearance and self-compassion on the practice of physical exercise and use of IPEDs during lockdown. Methods: An international online questionnaire was carried out using the Exercise Addiction Inventory (EAI), the Appearance Anxiety Inventory (AAI), and the Self-Compassion Scale (SCS) in addition to questions on the use of IPEDs. Results: The sample consisted of 3,161 (65% female) adults from Italy (41.1%), Spain (15.7%), the United Kingdom (UK) (12.0%), Lithuania (11.6%), Portugal (10.5%), Japan (5.5%), and Hungary (3.5%). The mean age was 35.05 years (SD = 12.10). Overall, 4.3% of the participants were found to engage in excessive or problematic exercise with peaks registered in the UK (11.0%) and Spain (5.4%). The sample reported the use of a wide range of drugs and medicines to boost image and performance (28%) and maintained use during the lockdown, mostly in Hungary (56.6%), Japan (46.8%), and the UK (33.8%), with 6.4% who started to use a new drug. Significant appearance anxiety levels were found across the sample, with 18.1% in Italy, 16.9% in Japan, and 16.7% in Portugal. Logistic regression models revealed a strong association between physical exercise and IPED use. Anxiety about appearance also significantly increased the probability of using IPEDs. However, self-compassion did not significantly predict such behavior. Anxiety about appearance and self-compassion were non-significant predictors associated with engaging in physical exercise. Discussion and Conclusion: This study identified risks of problematic exercising and appearance anxiety among the general population during the COVID-19 lockdown period across all the participating countries with significant gender differences. Such behaviors were positively associated with the unsupervised use of IPEDs, although no interaction between physical exercise and appearance anxiety was observed. Further considerations are needed to explore the impact of socially restrictive measures among vulnerable groups, and the implementation of more targeted responses.", "classifications": [ { "id": "Fujiwara", "label": "Group Fujiwara", "parent": "Fujiwara", "type": "group" }, { "id": "Fujiwara", "label": "Team Fujiwara", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Artemisa R.", "last_name": "Dores", "name": null }, { "creator_type": "author", "first_name": "Irene P.", "last_name": "Carvalho", "name": null }, { "creator_type": "author", "first_name": "Julius", "last_name": "Burkauskas", "name": null }, { "creator_type": "author", "first_name": "Pierluigi", "last_name": "Simonato", "name": null }, { "creator_type": "author", "first_name": "Ilaria", "last_name": "De Luca", "name": null }, { "creator_type": "author", "first_name": "Roisin", "last_name": "Mooney", "name": null }, { "creator_type": "author", "first_name": "Konstantinos", "last_name": "Ioannidis", "name": null }, { "creator_type": "author", "first_name": "M. Angeles", "last_name": "Gomez-Martinez", "name": null }, { "creator_type": "author", "first_name": "Zsolt", "last_name": "Demetrovics", "name": null }, { "creator_type": "author", "first_name": "Krisztina Edina", "last_name": "Abel", "name": null }, { "creator_type": "author", "first_name": "Attila", "last_name": "Szabo", "name": null }, { "creator_type": "author", "first_name": "Hironobu", "last_name": "Fujiwara", "name": null }, { "creator_type": "author", "first_name": "Mami", "last_name": "Shibata", "name": null }, { "creator_type": "author", "first_name": "Alejandra Rebeca Melero", "last_name": "Ventola", "name": null }, { "creator_type": "author", "first_name": "Eva Maria", "last_name": "Arroyo-Anllo", "name": null }, { "creator_type": "author", "first_name": "Ricardo M.", "last_name": "Santos-Labrador", "name": null }, { "creator_type": "author", "first_name": "Inga", "last_name": "Griskova-Bulanova", "name": null }, { "creator_type": "author", "first_name": "Aiste", "last_name": "Pranckeviciene", "name": null }, { "creator_type": "author", "first_name": "Kei", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Giovanni", "last_name": "Martinotti", "name": null }, { "creator_type": "author", "first_name": "Naomi A.", "last_name": "Fineberg", "name": null }, { "creator_type": "author", "first_name": "Fernando", "last_name": "Barbosa", "name": null }, { "creator_type": "author", "first_name": "Ornella", "last_name": "Corazza", "name": null } ], "identifiers": { "doi": { "normalized": "10.3389/fpsyt.2021.648501" }, "pmcid": { "normalized": "PMC7988429" }, "pmid": { "normalized": "33776822" } }, "mesh": [], "publication": { "conference_name": null, "date": "2021", "date_precision": "year", "issue": "", "normalized_date": "2021", "pages": "648501", "proceedings_title": null, "publisher": "", "title": "Frontiers in psychiatry", "volume": "12", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Exercise and Use of Enhancement Drugs at the Time of the COVID-19 Pandemic: A Multicultural Study on Coping Strategies During Self-Isolation and Related Risks.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Purpose: We aimed to examine the characteristics of imaging findings of adenocarcinoma in situ (AIS) and minimally invasive adenocarcinoma (MIA) in the lungs of smokers compared with those of non-smokers. Materials and methods: We included seven cases of AIS and 20 cases of MIA in lungs of smokers (pack-years ≥ 20) and the same number of cases of AIS and MIA in lungs of non-smokers (pack-years = 0). We compared the diameter of the entire lesion and solid component measured on computed tomography (CT) images, pathological size and invasive component diameter measured from pathological specimens, and CT values of the entire lesion and ground-glass opacity (GGO) portions between the smoker and non-smoker groups. Results: The diameters of AIS and MIA on CT images and pathological specimens of the smoker group were significantly larger than those of the non-smoker group (p = 0.036 and 0.008, respectively), whereas there was no significant difference in the diameter of the solid component on CT images or invasive component of pathological specimens between the two groups. Additionally, mean CT values of the entire lesion and GGO component of the lesions in the smoker group were significantly lower than those in the non-smoker group (p = 0.036 and 0.040, respectively). Conclusion: AIS and MIA in smoker’s lung tended to have larger lesion diameter and lower internal CT values compared with lesions in non-smoker’s lung. This study calls an attention on smoking status in CT-based diagnosis for early stage adenocarcinoma.", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Haruto", "last_name": "Sugawara", "name": null }, { "creator_type": "author", "first_name": "Hirokazu", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Akira", "last_name": "Kunimatsu", "name": null }, { "creator_type": "author", "first_name": "Osamu", "last_name": "Abe", "name": null }, { "creator_type": "author", "first_name": "Shun-ichi", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null }, { "creator_type": "author", "first_name": "Masahiko", "last_name": "Kusumoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1186/s12880-021-00705-1" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "34798844" } }, "mesh": [ { "descriptor": "Adenocarcinoma", "descriptor_ui": "D000230", "major_topic": false }, { "descriptor": "Adenocarcinoma in Situ", "descriptor_ui": "D065311", "major_topic": false }, { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Japan", "descriptor_ui": "D007564", "major_topic": false }, { "descriptor": "Lung Neoplasms", "descriptor_ui": "D008175", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Retrospective Studies", "descriptor_ui": "D012189", "major_topic": false }, { "descriptor": "Smokers", "descriptor_ui": "D000074285", "major_topic": true }, { "descriptor": "Tomography, X-Ray Computed", "descriptor_ui": "D014057", "major_topic": true } ], "publication": { "conference_name": null, "date": "2021", "date_precision": "year", "issue": "", "normalized_date": "2021", "pages": "", "proceedings_title": null, "publisher": "", "title": "BMC Medical Imaging", "volume": "21", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Adenocarcinoma in situ and minimally invasive adenocarcinoma in lungs of smokers: image feature differences from those in lungs of non-smokers.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Lactate dehydrogenase (LDH) catalyses the conversion of pyruvate to lactate and NADH to NAD+; it has two isoforms, LDHA and LDHB. LDHA is a promising target for cancer therapy, whereas LDHB is necessary for basal autophagy and cancer cell proliferation in oxidative and glycolytic cancer cells. To the best of our knowledge, selective inhibitors for LDHB have not yet been reported. Here, we developed a high-throughput mass spectrometry screening system using an LDHB enzyme assay by detecting NADH and NAD+. As a result, we identified a small-molecule LDHB selective inhibitor AXKO-0046, an indole derivative. This compound exhibited uncompetitive LDHB inhibition (EC50 = 42 nM). X-ray crystallography revealed that AXKO-0046 bound to the potential allosteric site away from the LDHB catalytic active site, suggesting that targeting the tetramerisation interface of the two dimers is critical for the enzymatic activity. AXKO-0046 and its derivatives can be used to validate LDHB-associated pathways in cancer metabolism.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Sachio", "last_name": "Shibata", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Sogabe", "name": null }, { "creator_type": "author", "first_name": "Masanori", "last_name": "Miwa", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Fujimoto", "name": null }, { "creator_type": "author", "first_name": "Nobuyuki", "last_name": "Takakura", "name": null }, { "creator_type": "author", "first_name": "Akihiko", "last_name": "Naotsuka", "name": null }, { "creator_type": "author", "first_name": "Shuji", "last_name": "Kitamura", "name": null }, { "creator_type": "author", "first_name": "Tomohiro", "last_name": "Kawamoto", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41598-021-00820-7" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "34725423" } }, "mesh": [ { "descriptor": "Crystallography, X-Ray", "descriptor_ui": "D018360", "major_topic": false }, { "descriptor": "Drug Discovery", "descriptor_ui": "D055808", "major_topic": false }, { "descriptor": "Enzyme Inhibitors", "descriptor_ui": "D004791", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Indoles", "descriptor_ui": "D007211", "major_topic": false }, { "descriptor": "Isoenzymes", "descriptor_ui": "D007527", "major_topic": false }, { "descriptor": "L-Lactate Dehydrogenase", "descriptor_ui": "D007770", "major_topic": false }, { "descriptor": "Models, Molecular", "descriptor_ui": "D008958", "major_topic": false }, { "descriptor": "Small Molecule Libraries", "descriptor_ui": "D054852", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021", "date_precision": "year", "issue": "", "normalized_date": "2021", "pages": "", "proceedings_title": null, "publisher": "", "title": "Scientific Reports", "volume": "11", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Identification of the first highly selective inhibitor of human lactate dehydrogenase B.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Food intake biomarkers can be critical tools that can be used to objectively assess dietary exposure for both epidemiological and clinical nutrition studies. While an accurate estimation of food intake is essential to unravel associations between the intake and specific health conditions, random and systematic errors affect self-reported assessments. This study aimed to clarify how habitual food intake influences the circulating plasma metabolome in a free-living Japanese regional population and to identify potential food intake biomarkers. To achieve this aim, we conducted a cross-sectional analysis as part of a large cohort study. From a baseline survey of the Tsuruoka Metabolome Cohort Study, 7,012 eligible male and female participants aged 40-69 years were chosen for this study. All data on patients' health status and dietary intake were assessed via a food frequency questionnaire, and plasma samples were obtained during an annual physical examination. Ninety-four charged plasma metabolites were measured using capillary electrophoresis mass spectrometry, by a non-targeted approach. Statistical analysis was performed using partial-least-square regression. A total of 21 plasma metabolites were likely to be associated with long-term food intake of nine food groups. In particular, the influential compounds in each food group were hydroxyproline for meat, trimethylamine-N-oxide for fish, choline for eggs, galactarate for dairy, cystine and betaine for soy products, threonate and galactarate for carotenoid-rich vegetables, proline betaine for fruits, quinate and trigonelline for coffee, and pipecolate for alcohol, and these were considered as prominent food intake markers in Japanese eating habits. A set of circulating plasma metabolites was identified as potential food intake biomarkers in the Japanese community-dwelling population. These results will open the way for the application of new reliable dietary assessment tools not by self-reported measurements but through objective quantification of biofluids.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Eriko", "last_name": "Shibutami", "name": null }, { "creator_type": "author", "first_name": "Ryota", "last_name": "Ishii", "name": null }, { "creator_type": "author", "first_name": "Sei", "last_name": "Harada", "name": null }, { "creator_type": "author", "first_name": "Ayako", "last_name": "Kurihara", "name": null }, { "creator_type": "author", "first_name": "Kazuyo", "last_name": "Kuwabara", "name": null }, { "creator_type": "author", "first_name": "Suzuka", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Miho", "last_name": "Iida", "name": null }, { "creator_type": "author", "first_name": "Miki", "last_name": "Akiyama", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Sugiyama", "name": null }, { "creator_type": "author", "first_name": "Akiyoshi", "last_name": "Hirayama", "name": null }, { "creator_type": "author", "first_name": "Asako", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Kaori", "last_name": "Amano", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Sugimoto", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Masaru", "last_name": "Tomita", "name": null }, { "creator_type": "author", "first_name": "Toru", "last_name": "Takebayashi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1371/journal.pone.0246456" }, "pmcid": { "normalized": "PMC7875413" }, "pmid": { "normalized": "33566801" } }, "mesh": [ { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Biomarkers", "descriptor_ui": "D015415", "major_topic": false }, { "descriptor": "Cohort Studies", "descriptor_ui": "D015331", "major_topic": false }, { "descriptor": "Cross-Sectional Studies", "descriptor_ui": "D003430", "major_topic": false }, { "descriptor": "Eating", "descriptor_ui": "D004435", "major_topic": true }, { "descriptor": "Feeding Behavior", "descriptor_ui": "D005247", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Japan", "descriptor_ui": "D007564", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Metabolome", "descriptor_ui": "D055442", "major_topic": false }, { "descriptor": "Metabolomics", "descriptor_ui": "D055432", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021", "date_precision": "year", "issue": "2", "normalized_date": "2021", "pages": "e0246456", "proceedings_title": null, "publisher": "", "title": "PloS one", "volume": "16", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Charged metabolite biomarkers of food intake assessed via plasma metabolomics in a population-based observational study in Japan.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Cancer cell populations consist of phenotypically heterogeneous cells. Growing evidence suggests that pre-existing phenotypic differences among cancer cells correlate with differential susceptibility to anticancer drugs and eventually lead to a relapse. Such phenotypic differences can arise not only externally driven by the environmental heterogeneity around individual cells but also internally by the intrinsic fluctuation of cells. However, the quantitative characteristics of intrinsic phenotypic heterogeneity emerging even under constant environments and their relevance to drug susceptibility remain elusive. Here we employed a microfluidic device, mammalian mother machine, for studying the intrinsic heterogeneity of growth dynamics of mouse lymphocytic leukemia cells (L1210) across tens of generations. The generation time of this cancer cell line had a distribution with a long tail and a heritability across generations. We determined that a minority of cell lineages exist in a slow-cycling state for multiple generations. These slow-cycling cell lineages had a higher chance of survival than the fast-cycling lineages under continuous exposure to the anticancer drug Mitomycin C. This result suggests that heritable heterogeneity in cancer cells' growth in a population influences their susceptibility to anticancer drugs.", "classifications": [ { "id": "JPMJCR1927", "label": "JPMJCR1927", "researcher": "Yuichi Wakamoto", "type": "grant" }, { "id": "Wakamoto", "label": "Group Wakamoto", "parent": "Wakamoto", "type": "group" }, { "id": "Wakamoto", "label": "Team Wakamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Akihisa", "last_name": "Seita", "name": null }, { "creator_type": "author", "first_name": "Hidenori", "last_name": "Nakaoka", "name": null }, { "creator_type": "author", "first_name": "Reiko", "last_name": "Okura", "name": null }, { "creator_type": "author", "first_name": "Yuichi", "last_name": "Wakamoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1371/journal.pone.0236534" }, "pmcid": { "normalized": "PMC7850478" }, "pmid": { "normalized": "33524064" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Antineoplastic Agents", "descriptor_ui": "D000970", "major_topic": false }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Cell Proliferation", "descriptor_ui": "D049109", "major_topic": false }, { "descriptor": "Drug Resistance, Neoplasm", "descriptor_ui": "D019008", "major_topic": false }, { "descriptor": "Leukemia", "descriptor_ui": "D007938", "major_topic": false }, { "descriptor": "Leukemia, Lymphoid", "descriptor_ui": "D007945", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Microfluidic Analytical Techniques", "descriptor_ui": "D046210", "major_topic": false }, { "descriptor": "Mitomycin", "descriptor_ui": "D016685", "major_topic": false }, { "descriptor": "Neoplasms", "descriptor_ui": "D009369", "major_topic": false }, { "descriptor": "Phenotype", "descriptor_ui": "D010641", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021", "date_precision": "year", "issue": "2", "normalized_date": "2021", "pages": "e0236534", "proceedings_title": null, "publisher": "", "title": "PloS one", "volume": "16", "year": 2021 }, "ssbd": { "database": [ "ssbd-database-000254" ], "repository": [ "ssbd-repos-000254" ] }, "title": "Intrinsic growth heterogeneity of mouse leukemia cells underlies differential susceptibility to a growth-inhibiting anticancer drug.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: Based on the theory of traditional Chinese medicine, Chinese herbs possess four different medicinal properties: hot, warm, cold, and cool. These serve as a reference guide for these herbal medicines. However, the molecular mechanisms supporting their relevance remain unclear. METHODS: We performed metabolomics based on capillary electrophoresis-time-of-flight mass spectrometry (CE-TOF/MS) and multivariate data analysis for the structural identification of compounds of cold- and hot-natured Chinese herbs. RESULTS: To this end, 30 selected herbs were analyzed and a total of 416 metabolites were identified via CE-TOF/MS, of which 193 compounds were detected in most herbs. The observed profiles offered the potential to understand the mechanism of association between the compounds and nature of the Chinese herbs. Comparison of the similarity in terms of chemical and molecular structures and content revealed that hot-natured herbs contained more nucleotides. In contrast, principal component analysis revealed the presence of more amino acid compounds in cold-natured herbs. CONCLUSION: Comparing the structural similarities between the samples using the Tanimoto coefficient revealed that a general non-specific structure was observed between cold- and hot-natured herbs; however, the distribution of the molecular groups seemed to contribute more toward the energy properties.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Jing", "last_name": "Guo", "name": null }, { "creator_type": "author", "first_name": "Jiaxiao", "last_name": "Wang", "name": null }, { "creator_type": "author", "first_name": "Keiko", "last_name": "Iino", "name": null }, { "creator_type": "author", "first_name": "Masaru", "last_name": "Tomita", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null } ], "identifiers": { "doi": { "normalized": "10.1155/2021/6646507" }, "pmcid": { "normalized": "PMC7954617" }, "pmid": { "normalized": "33747108" } }, "mesh": [], "publication": { "conference_name": null, "date": "2021", "date_precision": "year", "issue": "", "normalized_date": "2021", "pages": "6646507", "proceedings_title": null, "publisher": "", "title": "Evidence-based complementary and alternative medicine : eCAM", "volume": "2021", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Quantitative and Molecular Similarity Analyses of the Metabolites of Cold- and Hot-Natured Chinese Herbs.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "With the completion of the International Human Genome Project, we have entered what is known as the post-genome era, and efforts to apply genomic information to medicine have become more active. In particular, with the announcement of the Precision Medicine Initiative by U.S. President Barack Obama in his State of the Union address at the beginning of 2015, “precision medicine,” which aims to divide patients and potential patients into subgroups with respect to disease susceptibility, has become the focus of worldwide attention. The field of oncology is also actively adopting the precision oncology approach, which is based on molecular profiling, such as genomic information, to select the appropriate treatment. However, the current precision oncology is dominated by a method called targeted-gene panel (TGP), which uses next-generation sequencing (NGS) to analyze a limited number of specific cancer-related genes and suggest optimal treatments, but this method causes the problem that the number of patients who benefit from it is limited. In order to steadily develop precision oncology, it is necessary to integrate and analyze more detailed omics data, such as whole genome data and epigenome data. On the other hand, with the advancement of analysis technologies such as NGS, the amount of data obtained by omics analysis has become enormous, and artificial intelligence (AI) technologies, mainly machine learning (ML) technologies, are being actively used to make more efficient and accurate predictions. In this review, we will focus on whole genome sequencing (WGS) analysis and epigenome analysis, introduce the latest results of omics analysis using ML technologies for the development of precision oncology, and discuss the future prospects.", "classifications": [ { "id": "Hamamoto", "label": "Group Hamamoto", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Ken", "last_name": "Asada", "name": null }, { "creator_type": "author", "first_name": "Syuzo", "last_name": "Kaneko", "name": null }, { "creator_type": "author", "first_name": "Ken", "last_name": "Takasawa", "name": null }, { "creator_type": "author", "first_name": "Hidenori", "last_name": "Machino", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Norio", "last_name": "Shinkai", "name": null }, { "creator_type": "author", "first_name": "Ryo", "last_name": "Shimoyama", "name": null }, { "creator_type": "author", "first_name": "Masaaki", "last_name": "Komatsu", "name": null }, { "creator_type": "author", "first_name": "Ryuji", "last_name": "Hamamoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.3389/fonc.2021.666937" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "34055633" } }, "mesh": [], "publication": { "conference_name": null, "date": "2021", "date_precision": "year", "issue": "", "normalized_date": "2021", "pages": "", "proceedings_title": null, "publisher": "", "title": "Frontiers in Oncology", "volume": "11", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Integrated Analysis of Whole Genome and Epigenome Data Using Machine Learning Technology: Toward the Establishment of Precision Oncology.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Quantitative plant biology is an interdisciplinary field that builds on a long history of biomathematics and biophysics. Today, thanks to high spatiotemporal resolution tools and computational modelling, it sets a new standard in plant science. Acquired data, whether molecular, geometric or mechanical, are quantified, statistically assessed and integrated at multiple scales and across fields. They feed testable predictions that, in turn, guide further experimental tests. Quantitative features such as variability, noise, robustness, delays or feedback loops are included to account for the inner dynamics of plants and their interactions with the environment. Here, we present the main features of this ongoing revolution, through new questions around signalling networks, tissue topology, shape plasticity, biomechanics, bioenergetics, ecology and engineering. In the end, quantitative plant biology allows us to question and better understand our interactions with plants. In turn, this field opens the door to transdisciplinary projects with the society, notably through citizen science.", "classifications": [ { "id": "Ueda", "label": "Group Ueda", "parent": "Ueda", "type": "group" }, { "id": "Ueda", "label": "Team Ueda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Daphne", "last_name": "Autran", "name": null }, { "creator_type": "author", "first_name": "George W.", "last_name": "Bassel", "name": null }, { "creator_type": "author", "first_name": "Eunyoung", "last_name": "Chae", "name": null }, { "creator_type": "author", "first_name": "Daphne", "last_name": "Ezer", "name": null }, { "creator_type": "author", "first_name": "Ali", "last_name": "Ferjani", "name": null }, { "creator_type": "author", "first_name": "Christian", "last_name": "Fleck", "name": null }, { "creator_type": "author", "first_name": "Olivier", "last_name": "Hamant", "name": null }, { "creator_type": "author", "first_name": "Felix P.", "last_name": "Hartmann", "name": null }, { "creator_type": "author", "first_name": "Yuling", "last_name": "Jiao", "name": null }, { "creator_type": "author", "first_name": "Iain G.", "last_name": "Johnston", "name": null }, { "creator_type": "author", "first_name": "Dorota", "last_name": "Kwiatkowska", "name": null }, { "creator_type": "author", "first_name": "Boon L.", "last_name": "Lim", "name": null }, { "creator_type": "author", "first_name": "Ari Pekka", "last_name": "Mahonen", "name": null }, { "creator_type": "author", "first_name": "Richard J.", "last_name": "Morris", "name": null }, { "creator_type": "author", "first_name": "Bela M.", "last_name": "Mulder", "name": null }, { "creator_type": "author", "first_name": "Naomi", "last_name": "Nakayama", "name": null }, { "creator_type": "author", "first_name": "Ross", "last_name": "Sozzani", "name": null }, { "creator_type": "author", "first_name": "Lucia C.", "last_name": "Strader", "name": null }, { "creator_type": "author", "first_name": "Kirsten", "last_name": "Ten Tusscher", "name": null }, { "creator_type": "author", "first_name": "Minako", "last_name": "Ueda", "name": null }, { "creator_type": "author", "first_name": "Sebastian", "last_name": "Wolf", "name": null } ], "identifiers": { "doi": { "normalized": "10.1017/qpb.2021.8" }, "pmcid": { "normalized": "PMC10095877" }, "pmid": { "normalized": "37077212" } }, "mesh": [], "publication": { "conference_name": null, "date": "2021", "date_precision": "year", "issue": "", "normalized_date": "2021", "pages": "e10", "proceedings_title": null, "publisher": "", "title": "Quantitative plant biology", "volume": "2", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "What is quantitative plant biology?", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: Esophageal cancer often appears as postoperative metastasis or recurrence after radical surgery. Although we had previously reported that serum programmed cell death ligand 1 (PD-L1) level correlated with the prognosis of esophageal cancer, further novel biomarkers are required for more precise prediction of the prognosis. Proprotein convertase subtilisin/kexin type 9 (PCSK9) is associated with the cholesterol metabolism. But there was no report of relationship between serum PCSK9 antibody and cancer. Therefore, we investigated whether anti-PCSK9 antibodies could be a novel biomarker for solid cancer. METHODS: Serum levels of anti-PCSK9 antibodies and antigens in patients with solid cancer were analyzed using amplified luminescence proximity homogeneous assay-linked immunosorbent assay (AlphaLISA). The reactivity of serum antibodies against recombinant PCSK9 protein was investigated by Western blotting, and the expression of PCSK9 antigens in esophageal cancer tissues was examined by immunohistochemical staining. RESULTS: AlphaLISA showed that serum anti-PCSK9 antibody (s-PCSK9-Ab) levels were significantly higher in patients with esophageal cancer, gastric cancer, colorectal cancer, lung cancer, and breast cancer than in healthy donors, and patients with esophageal cancer had the highest levels. The presence of serum antibody in patients was confirmed by Western blotting. There was no apparent correlation between s-PCSK9-Ab and PCSK9 antigen levels. Immunohistochemical staining demonstrated the expression of PCSK9 antigen in both the cytoplasm and nuclear compartments of esophageal squamous cell carcinoma tissue but not in normal tissue. Compared with patients with low s-PCSK9-Ab levels, those with high s-PCSK9-Ab levels had a favorable postoperative prognosis after radical surgery for esophageal cancer. In the multivariate analysis, tumor depth and s-PCSK9-Ab level were identified as independent prognostic factors. In the univariate analysis of clinicopathological features, high PCSK9 antibody levels were not associated with sex, age, location, tumor depth, lymph node status, squamous cell carcinoma antigen, or p53-Ab, whereas they correlated significantly with PD-L1 levels, which were associated with unfavorable prognosis. Correlation between s-PCSK9-Ab and PD-L1 levels was also confirmed in the logistic regression analysis; therefore, low s-PCSK9-Ab levels could discriminate another poor prognosis group other than high-PD-L1 group. CONCLUSIONS: Patients with solid cancer had higher s-PCSK9-Ab levels than healthy donors. High s-PCSK9-Ab levels indicated better prognosis for overall survival after surgery in patients with esophageal cancer.", "classifications": [ { "id": "Suzuki", "label": "Group Suzuki", "parent": "Takekawa", "type": "group" }, { "id": "Takekawa", "label": "Team Takekawa", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Masaaki", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Takaki", "last_name": "Hiwasa", "name": null }, { "creator_type": "author", "first_name": "Yoko", "last_name": "Oshima", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Yajima", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Tatsuki", "last_name": "Nanami", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Sumazaki", "name": null }, { "creator_type": "author", "first_name": "Fumiaki", "last_name": "Shiratori", "name": null }, { "creator_type": "author", "first_name": "Kimihiko", "last_name": "Funahashi", "name": null }, { "creator_type": "author", "first_name": "Shu-Yang", "last_name": "Li", "name": null }, { "creator_type": "author", "first_name": "Yasuo", "last_name": "Iwadate", "name": null }, { "creator_type": "author", "first_name": "Hiroki", "last_name": "Yamagata", "name": null }, { "creator_type": "author", "first_name": "Byambasteren", "last_name": "Jambaljav", "name": null }, { "creator_type": "author", "first_name": "Minoru", "last_name": "Takemoto", "name": null }, { "creator_type": "author", "first_name": "Koutaro", "last_name": "Yokote", "name": null }, { "creator_type": "author", "first_name": "Hirotaka", "last_name": "Takizawa", "name": null }, { "creator_type": "author", "first_name": "Hideaki", "last_name": "Shimada", "name": null } ], "identifiers": { "doi": { "normalized": "10.3389/fonc.2021.708039" }, "pmcid": { "normalized": "PMC8421770" }, "pmid": { "normalized": "34504788" } }, "mesh": [], "publication": { "conference_name": null, "date": "2021", "date_precision": "year", "issue": "", "normalized_date": "2021", "pages": "708039", "proceedings_title": null, "publisher": "", "title": "Frontiers in oncology", "volume": "11", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Association of Serum Anti-PCSK9 Antibody Levels with Favorable Postoperative Prognosis in Esophageal Cancer.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The current standard murine model of bone metastasis by using intracardiac injection (IC) has some limitations despite the great utility of this model. This fact emphasizes the need for a new murine model to accelerate basic research of bone metastasis. The present protocol provides instructions on caudal artery (CA) injection that is an easy-to-use method to reliably construct a murine bone metastasis model with a variety type of cancer cell lines. Bioluminescence imaging visualized that cancer cells injected via the caudal artery in the tail were efficiently delivered to a hind limb bone, where it is a common site affected with bone metastasis in mice. CA injection rarely causes stress-induced acute death in mice and enables us to inject a large number of cancer cells, thereby greatly increasing the frequency of bone metastasis in hind limb bones. Importantly, CA injection is technically as easy as tail vein injection and causes no lethal stress, indicating that it is a model that also contributes to animal welfare. CA injection model, therefore, could represent a powerful tool for many researchers to study molecular mechanisms of bone metastasis in mice.", "classifications": [ { "id": "Kuchimaru", "label": "Group Kuchimaru", "parent": "Shintaku", "type": "group" }, { "id": "Shintaku", "label": "Team Shintaku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Takahiro", "last_name": "Kuchimaru", "name": null }, { "creator_type": "author", "first_name": "Shinae", "last_name": "Kizaka-Kondoh", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/978-1-0716-1258-3_4" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "34050460" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Bone Neoplasms", "descriptor_ui": "D001859", "major_topic": false }, { "descriptor": "Carcinoma, Lewis Lung", "descriptor_ui": "D018827", "major_topic": false }, { "descriptor": "Carotid Arteries", "descriptor_ui": "D002339", "major_topic": false }, { "descriptor": "Image Processing, Computer-Assisted", "descriptor_ui": "D007091", "major_topic": false }, { "descriptor": "Luminescent Measurements", "descriptor_ui": "D008163", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021", "date_precision": "year", "issue": "", "normalized_date": "2021", "pages": "37-42", "proceedings_title": null, "publisher": "", "title": "Methods in molecular biology (Clifton, N.J.)", "volume": "2274", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "A Murine Bone Metastasis Model Using Caudal Artery Injection and Bioluminescence Imaging.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "This study assesses the gender differences in health and anxiety, especially pertaining to mental health problems and time-course effects. We surveyed 121 patients admitted to a hospital with a COVID-19 diagnosis between March 1 and August 31, 2020. Their mental status was evaluated on admission using the Japanese General Health Questionnaire-28 (GHQ-28) and State-Trait Anxiety Inventory-Form JYZ (STAI). The patients were divided into two groups depending on the period of prevalence, that is, the first and second waves of the pandemic in Japan (from the beginning of March to the end of May 2020, Time 1 = T1; and from the beginning of June to the end of August 2020, Time 2 = T2). A multivariate analysis of covariance revealed significant differences in gender by time interactions in the GHQ-28 subscale \"Insomnia and anxiety\" and STAI subscale \"State-Anxiety.\" Post-hoc t-tests revealed that the scores of \"Insomnia and Anxiety\" and \"State-Anxiety\" were higher in women than in men at T1. However, no difference was observed at T2. Further, \"Insomnia and Anxiety\" and \"State-Anxiety\" were significantly higher at T1 than at T2 in female patients. There was no significant difference in males. Thus, female patients were more anxious and depressed in the early phase of the pandemic, whereas male patients had difficulties in coping with anxiety. We suggest more gender-specific mental care, particularly for women at the early stages of infection.", "classifications": [ { "id": "Fujiwara", "label": "Group Fujiwara", "parent": "Fujiwara", "type": "group" }, { "id": "Fujiwara", "label": "Team Fujiwara", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Ryo", "last_name": "Tsukamoto", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Kataoka", "name": null }, { "creator_type": "author", "first_name": "Koichi", "last_name": "Mino", "name": null }, { "creator_type": "author", "first_name": "Naoki", "last_name": "Ishibashi", "name": null }, { "creator_type": "author", "first_name": "Mariko", "last_name": "Shibata", "name": null }, { "creator_type": "author", "first_name": "Hiroo", "last_name": "Matsuo", "name": null }, { "creator_type": "author", "first_name": "Hironobu", "last_name": "Fujiwara", "name": null } ], "identifiers": { "doi": { "normalized": "10.3389/fpubh.2021.708965" }, "pmcid": { "normalized": "PMC8563575" }, "pmid": { "normalized": "34746076" } }, "mesh": [ { "descriptor": "Anxiety", "descriptor_ui": "D001007", "major_topic": false }, { "descriptor": "COVID-19", "descriptor_ui": "D000086382", "major_topic": true }, { "descriptor": "COVID-19 Testing", "descriptor_ui": "D000086742", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Inpatients", "descriptor_ui": "D007297", "major_topic": false }, { "descriptor": "Japan", "descriptor_ui": "D007564", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Pandemics", "descriptor_ui": "D058873", "major_topic": true }, { "descriptor": "SARS-CoV-2", "descriptor_ui": "D000086402", "major_topic": false }, { "descriptor": "Sex Factors", "descriptor_ui": "D012737", "major_topic": false }, { "descriptor": "Surveys and Questionnaires", "descriptor_ui": "D011795", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021", "date_precision": "year", "issue": "", "normalized_date": "2021", "pages": "708965", "proceedings_title": null, "publisher": "", "title": "Frontiers in public health", "volume": "9", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Gender Differences in Anxiety Among COVID-19 Inpatients Under Isolation: A Questionnaire Survey During the First and Second Waves of the COVID-19 Pandemic in Japan.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The squamous–columnar junction (SCJ) is a boundary consisting of precisely positioned transitional epithelium between the squamous and columnar epithelium. Transitional epithelium is a hotspot for precancerous lesions, and is therefore clinically important; however, the origins and physiological properties of transitional epithelium have not been fully elucidated. Here, by using mouse genetics, lineage tracing, and organoid culture, we examine the development of the SCJ in the mouse stomach, and thus define the unique features of transitional epithelium. We find that two transcription factors, encoded by Sox2 and Gata4, specify primitive transitional epithelium into squamous and columnar epithelium. The proximal–distal segregation of Sox2 and Gata4 expression establishes the boundary of the unspecified transitional epithelium between committed squamous and columnar epithelium. Mechanistically, Gata4-mediated expression of the morphogen Fgf10 in the distal stomach and Sox2-mediated Fgfr2 expression in the proximal stomach induce the intermediate regional activation of MAPK/ERK, which prevents the differentiation of transitional epithelial cells within the SCJ boundary. Our results have implications for tissue regeneration and tumorigenesis, which are related to the SCJ.", "classifications": [ { "id": "Yamamoto", "label": "Group Yamamoto", "parent": "Toyoshima", "type": "group" }, { "id": "Toyoshima", "label": "Team Toyoshima", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Nao", "last_name": "Sankoda", "name": null }, { "creator_type": "author", "first_name": "Wataru", "last_name": "Tanabe", "name": null }, { "creator_type": "author", "first_name": "Akito", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Hirofumi", "last_name": "Shibata", "name": null }, { "creator_type": "author", "first_name": "Knut", "last_name": "Woltjen", "name": null }, { "creator_type": "author", "first_name": "Tsutomu", "last_name": "Chiba", "name": null }, { "creator_type": "author", "first_name": "Hironori", "last_name": "Haga", "name": null }, { "creator_type": "author", "first_name": "Yoshiharu", "last_name": "Sakai", "name": null }, { "creator_type": "author", "first_name": "Masaki", "last_name": "Mandai", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Yasuhiro", "last_name": "Yamada", "name": null }, { "creator_type": "author", "first_name": "Shinji", "last_name": "Uemoto", "name": null }, { "creator_type": "author", "first_name": "Yoshiya", "last_name": "Kawaguchi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41467-021-20906-0" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "33495473" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Epithelial Cells", "descriptor_ui": "D004847", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Gastric Mucosa", "descriptor_ui": "D005753", "major_topic": false }, { "descriptor": "GATA4 Transcription Factor", "descriptor_ui": "D050991", "major_topic": false }, { "descriptor": "Gene Expression Regulation", "descriptor_ui": "D005786", "major_topic": true }, { "descriptor": "Intercellular Junctions", "descriptor_ui": "D007365", "major_topic": false }, { "descriptor": "Keratin-7", "descriptor_ui": "D053552", "major_topic": false }, { "descriptor": "MAP Kinase Signaling System", "descriptor_ui": "D020935", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, 129 Strain", "descriptor_ui": "D057507", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Inbred ICR", "descriptor_ui": "D008813", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Mice, Transgenic", "descriptor_ui": "D008822", "major_topic": false }, { "descriptor": "SOXB1 Transcription Factors", "descriptor_ui": "D055748", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021", "date_precision": "year", "issue": "", "normalized_date": "2021", "pages": "", "proceedings_title": null, "publisher": "", "title": "Nature Communications", "volume": "12", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Epithelial expression of Gata4 and Sox2 regulates specification of the squamous–columnar junction via MAPK/ERK signaling in mice.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Robust induction of cancer-antigen-specific CD8(+) T cells is essential for the success of cancer peptide vaccines, which are composed of a peptide derived from a cancer-specific antigen and an immune-potentiating adjuvant, such as a Toll-like receptor (TLR) agonist. Efficient delivery of a vaccine antigen and an adjuvant to antigen-presenting cells in the draining lymph nodes (LNs) holds key to maximize vaccine efficacy. Here, we developed S-540956, a novel TLR9-agonistic adjuvant consisting of B-type CpG ODN2006 (also known as CpG7909), annealed to its complementary sequence oligodeoxynucleotide (ODN) conjugated to a lipid; it could target both a cancer peptide antigen and a CpG-adjuvant in the draining LNs. S-540956 accumulation in the draining LNs and activation of plasmacytoid dendritic cells (pDCs) were significantly higher than that of ODN2006. Mechanistic analysis revealed that S-540956 enhanced the induction of MHC class I peptide-specific CD8(+) T cell responses via TLR9 in a CD4(+) T cell-independent manner. In mice, the therapeutic effect of S-540956-adjuvanted with a human papillomavirus (HPV)-E7 peptide vaccine against HPV-E7-expressing TC-1 tumors was significantly better than that of an ODN2006-adjuvanted vaccine. Our findings demonstrate a novel adjuvant discovery with the complementary strand conjugated to a lipid, which enabled draining LN targeting and increased ODN2006 accumulation in draining LNs, thereby enhancing the adjuvant effect. Our findings imply that S-540956 is a promising adjuvant for cancer peptide vaccines and has a high potential for applications in various vaccines, including recombinant protein vaccines.", "classifications": [ { "id": "Yamamoto", "label": "Group Yamamoto", "parent": "Toyoshima", "type": "group" }, { "id": "Toyoshima", "label": "Team Toyoshima", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Takayuki", "last_name": "Nakagawa", "name": null }, { "creator_type": "author", "first_name": "Tetsuya", "last_name": "Tanino", "name": null }, { "creator_type": "author", "first_name": "Motoyasu", "last_name": "Onishi", "name": null }, { "creator_type": "author", "first_name": "Soichi", "last_name": "Tofukuji", "name": null }, { "creator_type": "author", "first_name": "Takayuki", "last_name": "Kanazawa", "name": null }, { "creator_type": "author", "first_name": "Yukichi", "last_name": "Ishioka", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Itoh", "name": null }, { "creator_type": "author", "first_name": "Akira", "last_name": "Kugimiya", "name": null }, { "creator_type": "author", "first_name": "Kazufumi", "last_name": "Katayama", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Morio", "last_name": "Nagira", "name": null }, { "creator_type": "author", "first_name": "Ken J.", "last_name": "Ishii", "name": null } ], "identifiers": { "doi": { "normalized": "10.3389/fimmu.2021.803090" }, "pmcid": { "normalized": "PMC8735836" }, "pmid": { "normalized": "35003132" } }, "mesh": [ { "descriptor": "Adjuvants, Vaccine", "descriptor_ui": "D000089582", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cancer Vaccines", "descriptor_ui": "D019496", "major_topic": false }, { "descriptor": "CD8-Positive T-Lymphocytes", "descriptor_ui": "D018414", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Dendritic Cells", "descriptor_ui": "D003713", "major_topic": false }, { "descriptor": "DNA", "descriptor_ui": "D004247", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Immunization", "descriptor_ui": "D007114", "major_topic": false }, { "descriptor": "Lung Neoplasms", "descriptor_ui": "D008175", "major_topic": false }, { "descriptor": "Lymphocyte Activation", "descriptor_ui": "D008213", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Neoplasms, Experimental", "descriptor_ui": "D009374", "major_topic": false }, { "descriptor": "Oligodeoxyribonucleotides", "descriptor_ui": "D009838", "major_topic": false }, { "descriptor": "Papillomavirus E7 Proteins", "descriptor_ui": "D050725", "major_topic": false }, { "descriptor": "Sentinel Lymph Node", "descriptor_ui": "D000071036", "major_topic": false }, { "descriptor": "Surface-Active Agents", "descriptor_ui": "D013501", "major_topic": false }, { "descriptor": "Toll-Like Receptor 9", "descriptor_ui": "D051217", "major_topic": false }, { "descriptor": "Vaccines, Subunit", "descriptor_ui": "D022223", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021", "date_precision": "year", "issue": "", "normalized_date": "2021", "pages": "803090", "proceedings_title": null, "publisher": "", "title": "Frontiers in immunology", "volume": "12", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "S-540956, a CpG Oligonucleotide Annealed to a Complementary Strand With an Amphiphilic Chain Unit, Acts as a Potent Cancer Vaccine Adjuvant by Targeting Draining Lymph Nodes.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Malignant pleural mesothelioma (MPM) is an invasive malignancy that develops in the pleural cavity, and antifolates are used as chemotherapeutics for treating. The majority of antifolates, including pemetrexed (PMX), inhibit enzymes involved in purine and pyrimidine synthesis. MPM patients frequently develop drug resistance in clinical practice, however the associated drug-resistance mechanism is not well understood. This study was aimed to elucidate the mechanism underlying resistance to PMX in MPM cell lines. We found that among the differentially expressed genes associated with drug resistance (determined by RNA sequencing), TYMS expression was higher in the established resistant cell lines than in the parental cell lines. Knocking down TYMS expression significantly reduced drug resistance in the resistant cell lines. Conversely, TYMS overexpression significantly increased drug resistance in the parental cells. Metabolomics analysis revealed that the levels of dTMP were higher in the resistant cell lines than in the parental cell lines; however, resistant cells showed no changes in dTTP levels after PMX treatment. We found that the nucleic acid-biosynthetic pathway is important for predicting the efficacy of PMX in MPM cells. The results of chromatin immunoprecipitation-quantitative polymerase chain reaction (ChIP-qPCR) assays suggested that H3K27 acetylation in the 5'-UTR of TYMS may promote its expression in drug-resistant cells. Our findings indicate that the intracellular levels of dTMP are potential biomarkers for the effective treatment of patients with MPM and suggest the importance of regulatory mechanisms of TYMS expression in the disease.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yuzo", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Masaru", "last_name": "Tomita", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Ochiai", "name": null }, { "creator_type": "author", "first_name": "Hideki", "last_name": "Makinoshima", "name": null } ], "identifiers": { "doi": { "normalized": "10.3389/fphar.2021.718675" }, "pmcid": { "normalized": "PMC8504579" }, "pmid": { "normalized": "34646134" } }, "mesh": [], "publication": { "conference_name": null, "date": "2021", "date_precision": "year", "issue": "", "normalized_date": "2021", "pages": "718675", "proceedings_title": null, "publisher": "", "title": "Frontiers in pharmacology", "volume": "12", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Upregulation of Thymidylate Synthase Induces Pemetrexed Resistance in Malignant Pleural Mesothelioma.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Integrin regulation by Rap1 is indispensable for lymphocyte recirculation. In mice having B-cell-specific Rap1a/b double knockouts (DKO), the number of B cells in lymph nodes decreased to approximately 4% of that of control mice, and B cells were present in the spleen and blood. Upon the immunization with NP-CGG, DKO mice demonstrated the defective GC formation in the spleen, and the reduced NP-specific antibody production. In vitro, Rap1 deficiency impaired the movement of activated B cells along the gradients of chemoattractants known to be critical for their localization in the follicles. Furthermore, B-1a cells were almost completely absent in the peritoneal cavity, spleen and blood of adult DKO mice, and the number of B-cell progenitor/precursor (B-p) were reduced in neonatal and fetal livers. However, DKO B-ps normally proliferated, and differentiated into IgM(+) cells in the presence of IL-7. CXCL12-dependent migration of B-ps on the VCAM-1 was severely impaired by Rap1 deficiency. Immunostaining study of fetal livers revealed defects in the co-localization of DKO B-ps and IL-7-producing stromal cells. This study proposes that the profound effects of Rap1-deficiency on humoral responses and B-1a cell generation may be due to or in part caused by impairments of the chemoattractant-dependent positioning and the contact with stromal cells.", "classifications": [ { "id": "Sawai", "label": "Group Sawai", "parent": "Sawai", "type": "group" }, { "id": "Sawai", "label": "Team Sawai", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Sayaka", "last_name": "Ishihara", "name": null }, { "creator_type": "author", "first_name": "Tsuyoshi", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Risa", "last_name": "Sugioka", "name": null }, { "creator_type": "author", "first_name": "Ryota", "last_name": "Miwa", "name": null }, { "creator_type": "author", "first_name": "Haruka", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Ryota", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Hidehiro", "last_name": "Fukuyama", "name": null }, { "creator_type": "author", "first_name": "Akihiko", "last_name": "Nakajima", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Sawai", "name": null }, { "creator_type": "author", "first_name": "Ai", "last_name": "Kotani", "name": null }, { "creator_type": "author", "first_name": "Koko", "last_name": "Katagiri", "name": null } ], "identifiers": { "doi": { "normalized": "10.3389/fimmu.2021.624419" }, "pmcid": { "normalized": "PMC8203927" }, "pmid": { "normalized": "34140948" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "B-Lymphocytes", "descriptor_ui": "D001402", "major_topic": false }, { "descriptor": "Chemokine CXCL12", "descriptor_ui": "D054377", "major_topic": false }, { "descriptor": "Chemotaxis, Leukocyte", "descriptor_ui": "D002634", "major_topic": true }, { "descriptor": "gamma-Globulins", "descriptor_ui": "D005719", "major_topic": false }, { "descriptor": "Germinal Center", "descriptor_ui": "D018858", "major_topic": false }, { "descriptor": "Immunity, Humoral", "descriptor_ui": "D056724", "major_topic": false }, { "descriptor": "Immunization", "descriptor_ui": "D007114", "major_topic": false }, { "descriptor": "Intercellular Adhesion Molecule-1", "descriptor_ui": "D018799", "major_topic": false }, { "descriptor": "Liver", "descriptor_ui": "D008099", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Precursor Cells, B-Lymphoid", "descriptor_ui": "D054448", "major_topic": false }, { "descriptor": "rap GTP-Binding Proteins", "descriptor_ui": "D020668", "major_topic": false }, { "descriptor": "rap1 GTP-Binding Proteins", "descriptor_ui": "D020827", "major_topic": false }, { "descriptor": "Spleen", "descriptor_ui": "D013154", "major_topic": false }, { "descriptor": "Vascular Cell Adhesion Molecule-1", "descriptor_ui": "D019010", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021", "date_precision": "year", "issue": "", "normalized_date": "2021", "pages": "624419", "proceedings_title": null, "publisher": "", "title": "Frontiers in immunology", "volume": "12", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Rap1 Is Essential for B-Cell Locomotion, Germinal Center Formation and Normal B-1a Cell Population.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The clinical sequencing of tumors is usually performed on formalin-fixed, paraffin-embedded samples and results in many sequencing errors. We identified that most of these errors are detected in chimeric reads caused by single-strand DNA molecules with microhomology. During the end-repair step of library preparation, mutations are introduced by the mis-annealing of two single-strand DNA molecules comprising homologous sequences. The mutated bases are distributed unevenly near the ends in the individual reads. Our filtering pipeline, MicroSEC, focuses on the uneven distribution of mutations in each read and removes the sequencing errors in formalin-fixed, paraffin-embedded samples without over-eliminating the mutations detected also in fresh frozen samples. Amplicon-based sequencing using 97 mutations confirmed that the sensitivity and specificity of MicroSEC were 97% (95% confidence interval: 82–100%) and 96% (95% confidence interval: 88–99%), respectively. Our pipeline will increase the reliability of the clinical sequencing and advance the cancer research using formalin-fixed, paraffin-embedded samples.", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Masachika", "last_name": "Ikegami", "name": null }, { "creator_type": "author", "first_name": "Shinji", "last_name": "Kohsaka", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Hirose", "name": null }, { "creator_type": "author", "first_name": "Toshihide", "last_name": "Ueno", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Inoue", "name": null }, { "creator_type": "author", "first_name": "Naoki", "last_name": "Kanomata", "name": null }, { "creator_type": "author", "first_name": "Hideko", "last_name": "Yamauchi", "name": null }, { "creator_type": "author", "first_name": "Taisuke", "last_name": "Mori", "name": null }, { "creator_type": "author", "first_name": "Shigeki", "last_name": "Sekine", "name": null }, { "creator_type": "author", "first_name": "Yoshihiro", "last_name": "Inamoto", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Sakae", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Mano", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s42003-021-02930-4" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "34912045" } }, "mesh": [ { "descriptor": "Filtration", "descriptor_ui": "D005374", "major_topic": false }, { "descriptor": "Formaldehyde", "descriptor_ui": "D005557", "major_topic": false }, { "descriptor": "Gene Library", "descriptor_ui": "D015723", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": true }, { "descriptor": "Paraffin Embedding", "descriptor_ui": "D016612", "major_topic": false }, { "descriptor": "Reproducibility of Results", "descriptor_ui": "D015203", "major_topic": false }, { "descriptor": "Sensitivity and Specificity", "descriptor_ui": "D012680", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021", "date_precision": "year", "issue": "", "normalized_date": "2021", "pages": "", "proceedings_title": null, "publisher": "", "title": "Communications Biology", "volume": "4", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "MicroSEC filters sequence errors for formalin-fixed and paraffin-embedded samples.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Background: Miliary pulmonary metastasis characterized by tiny nodules is a rare metastatic pattern in advanced non-small cell lung cancer (NSCLC) and is usually seen in patients harboring an EGFR mutation, and amylase-producing lung cancer is highly uncommon and rarely reported in NSCLC patients who have an EGFR mutation. Case: A 32-year-old Japanese female was found to have miliary pulmonary nodules throughout both lung fields on a chest x-ray examination during an annual health check-up. Further examination by computed tomography (CT) revealed diffuse, bilateral, miliary nodules. Blood tests showed no increased tumor marker levels, but there was a significantly increased serum amylase level. A diagnosis of ALK-rearranged adenocarcinoma was made based on the results of a mediastinal lymph node biopsy obtained by endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA). Treatment with alectinib resulted in rapid regression of the CT shadows and a reduction in the patient’s serum amylase level. Conclusion: We have reported a case of ALK-rearranged NSCLC with a miliary pulmonary metastasis pattern that was sensitive to alectinib and in which the serum amylase level decreased in response to treatment with alectinib. Young patients with miliary pulmonary metastasis should be checked for all driver mutations.", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Hironori", "last_name": "Satoh", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Okuma", "name": null }, { "creator_type": "author", "first_name": "Jumpei", "last_name": "Kashima", "name": null }, { "creator_type": "author", "first_name": "Aya", "last_name": "Konnno-Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null }, { "creator_type": "author", "first_name": "Yuichiro", "last_name": "Ohe", "name": null } ], "identifiers": { "doi": { "normalized": "10.2147/ott.s300229" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "33958877" } }, "mesh": [], "publication": { "conference_name": null, "date": "2021", "date_precision": "year", "issue": "", "normalized_date": "2021", "pages": "2911-2915", "proceedings_title": null, "publisher": "", "title": "OncoTargets and therapy", "volume": "14", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Alectinib for Miliary Lung Metastasis in ALK-Positive Lung Adenocarcinoma.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Transient receptor potential (TRP) channels, especially canonical TRP channel subfamily members 3 (TRPC3) and 6 (TRPC6), have gained attention as a putative therapeutic target of heart failure. Moreover, TRPC3 and TRPC6 channels are physiologically important for maintaining cellular homeostasis. How TRPC3/C6 channels alter intracellular signaling from adaptation to maladaptation, has been discussed for many years. We have recently shown that the formation of a protein signal complex between TRPC3 and NADPH oxidase (Nox) 2 caused by environmental stresses (e.g., hypoxia, nutritional deficiency, and anti-cancer drug treatment) promotes Nox2-dependent reactive oxygen species production and cardiac stiffness, including myocardial atrophy and interstitial fibrosis, in rodents. In fact, pharmacological prevention of the TRPC3 -Nox2 protein complex can maintain cardiac flexibility in mice after anti-cancer drug treatment. In this mini-review, we discuss the relationship between TRPC3/C6 channels and cardiovascular disease, and propose a new therapeutic strategy by focusing on pathology-specific protein-protein interactions.", "classifications": [ { "id": "Nishida", "label": "Group Nishida", "parent": "Nishida", "type": "group" }, { "id": "Nishimura", "label": "Group Nishimura", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Kazuhiro", "last_name": "Nishiyama", "name": null }, { "creator_type": "author", "first_name": "Tomohiro", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Akiyuki", "last_name": "Nishimura", "name": null }, { "creator_type": "author", "first_name": "Motohiro", "last_name": "Nishida", "name": null } ], "identifiers": { "doi": { "normalized": "10.2174/1874467213666200407090121" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "32264816" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Atrophy", "descriptor_ui": "D001284", "major_topic": false }, { "descriptor": "Biomarkers", "descriptor_ui": "D015415", "major_topic": false }, { "descriptor": "Databases, Factual", "descriptor_ui": "D016208", "major_topic": false }, { "descriptor": "Heart Failure", "descriptor_ui": "D006333", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Molecular Targeted Therapy", "descriptor_ui": "D058990", "major_topic": false }, { "descriptor": "Myocytes, Cardiac", "descriptor_ui": "D032383", "major_topic": false }, { "descriptor": "NADPH Oxidase 2", "descriptor_ui": "D000074662", "major_topic": false }, { "descriptor": "NADPH Oxidases", "descriptor_ui": "D019255", "major_topic": false }, { "descriptor": "Protein Binding", "descriptor_ui": "D011485", "major_topic": false }, { "descriptor": "Reactive Oxygen Species", "descriptor_ui": "D017382", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "TRPC Cation Channels", "descriptor_ui": "D050052", "major_topic": false }, { "descriptor": "TRPC6 Cation Channel", "descriptor_ui": "D000074287", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021", "date_precision": "year", "issue": "2", "normalized_date": "2021", "pages": "123-131", "proceedings_title": null, "publisher": "", "title": "Current molecular pharmacology", "volume": "14", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "TRPC3-Based Protein Signaling Complex as a Therapeutic Target of Myocardial Atrophy.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "In vivo reprogramming provokes a wide range of cell fate conversion. Here, we discover that in vivo induction of higher levels of OSKM in mouse somatic cells leads to increased expression of primordial germ cell (PGC)-related genes and provokes genome-wide erasure of genomic imprinting, which takes place exclusively in PGCs. Moreover, the in vivo OSKM reprogramming results in development of cancer that resembles human germ cell tumors. Like a subgroup of germ cell tumors, propagated tumor cells can differentiate into trophoblasts. Moreover, these tumor cells give rise to induced pluripotent stem cells (iPSCs) with expanded differentiation potential into trophoblasts. Remarkably, the tumor-derived iPSCs are able to contribute to non-neoplastic somatic cells in adult mice. Mechanistically, DMRT1, which is expressed in PGCs, drives the reprogramming and propagation of the tumor cells in vivo. Furthermore, the DMRT1-related epigenetic landscape is associated with trophoblast competence of the reprogrammed cells and provides a therapeutic target for germ cell tumors. These results reveal an unappreciated route for somatic cell reprogramming and underscore the impact of reprogramming in development of germ cell tumors.", "classifications": [ { "id": "Yamamoto", "label": "Group Yamamoto", "parent": "Toyoshima", "type": "group" }, { "id": "Toyoshima", "label": "Team Toyoshima", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Jumpei", "last_name": "Taguchi", "name": null }, { "creator_type": "author", "first_name": "Hirofumi", "last_name": "Shibata", "name": null }, { "creator_type": "author", "first_name": "Mio", "last_name": "Kabata", "name": null }, { "creator_type": "author", "first_name": "Masaki", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Kei", "last_name": "Fukuda", "name": null }, { "creator_type": "author", "first_name": "Akito", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Sho", "last_name": "Ohta", "name": null }, { "creator_type": "author", "first_name": "Tomoyo", "last_name": "Ukai", "name": null }, { "creator_type": "author", "first_name": "Kanae", "last_name": "Mitsunaga", "name": null }, { "creator_type": "author", "first_name": "Yosuke", "last_name": "Yamada", "name": null }, { "creator_type": "author", "first_name": "So I.", "last_name": "Nagaoka", "name": null }, { "creator_type": "author", "first_name": "Sho", "last_name": "Yamazawa", "name": null }, { "creator_type": "author", "first_name": "Kotaro", "last_name": "Ohnishi", "name": null }, { "creator_type": "author", "first_name": "Knut", "last_name": "Woltjen", "name": null }, { "creator_type": "author", "first_name": "Tetsuo", "last_name": "Ushiku", "name": null }, { "creator_type": "author", "first_name": "Manabu", "last_name": "Ozawa", "name": null }, { "creator_type": "author", "first_name": "Mitinori", "last_name": "Saitou", "name": null }, { "creator_type": "author", "first_name": "Yoichi", "last_name": "Shinkai", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Yasuhiro", "last_name": "Yamada", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41467-021-25249-4" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "34413299" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Animals, Genetically Modified", "descriptor_ui": "D030801", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Cellular Reprogramming", "descriptor_ui": "D065150", "major_topic": false }, { "descriptor": "Epigenesis, Genetic", "descriptor_ui": "D044127", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Genomic Imprinting", "descriptor_ui": "D018392", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Induced Pluripotent Stem Cells", "descriptor_ui": "D057026", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred ICR", "descriptor_ui": "D008813", "major_topic": false }, { "descriptor": "Neoplasms", "descriptor_ui": "D009369", "major_topic": false }, { "descriptor": "Neoplasms, Germ Cell and Embryonal", "descriptor_ui": "D009373", "major_topic": false }, { "descriptor": "Transcription Factors", "descriptor_ui": "D014157", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021", "date_precision": "year", "issue": "", "normalized_date": "2021", "pages": "", "proceedings_title": null, "publisher": "", "title": "Nature Communications", "volume": "12", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "DMRT1-mediated reprogramming drives development of cancer resembling human germ cell tumors with features of totipotency.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Macroautophagy (hereafter called autophagy) is a highly conserved physiological process that degrades over-abundant or damaged organelles, large protein aggregates and invading pathogens via the lysosomal system (the vacuole in plants and yeast). Autophagy is generally induced by stress, such as oxygen-, energy- or amino acid-deprivation, irradiation, drugs, etc. In addition to non-selective bulk degradation, autophagy also occurs in a selective manner, recycling specific organelles, such as mitochondria, peroxisomes, ribosomes, endoplasmic reticulum (ER), lysosomes, nuclei, proteasomes and lipid droplets (LDs). This capability makes selective autophagy a major process in maintaining cellular homeostasis. The dysfunction of selective autophagy is implicated in neurodegenerative diseases (NDDs), tumorigenesis, metabolic disorders, heart failure, etc. Considering the importance of selective autophagy in cell biology, we systemically review the recent advances in our understanding of this process and its regulatory mechanisms. We emphasize the 'cargo-ligand-receptor' model in selective autophagy for specific organelles or cellular components in yeast and mammals, with a focus on mitophagy and ER-phagy, which are finely described as types of selective autophagy. Additionally, we highlight unanswered questions in the field, helping readers focus on the research blind spots that need to be broken.", "classifications": [ { "id": "Okamoto", "label": "Group Okamoto", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Wen", "last_name": "Li", "name": null }, { "creator_type": "author", "first_name": "Pengcheng", "last_name": "He", "name": null }, { "creator_type": "author", "first_name": "Yuge", "last_name": "Huang", "name": null }, { "creator_type": "author", "first_name": "Yi-Fang", "last_name": "Li", "name": null }, { "creator_type": "author", "first_name": "Jiahong", "last_name": "Lu", "name": null }, { "creator_type": "author", "first_name": "Min", "last_name": "Li", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Kurihara", "name": null }, { "creator_type": "author", "first_name": "Zhuo", "last_name": "Luo", "name": null }, { "creator_type": "author", "first_name": "Tian", "last_name": "Meng", "name": null }, { "creator_type": "author", "first_name": "Mashun", "last_name": "Onishi", "name": null }, { "creator_type": "author", "first_name": "Changle", "last_name": "Ma", "name": null }, { "creator_type": "author", "first_name": "Lei", "last_name": "Jiang", "name": null }, { "creator_type": "author", "first_name": "Yongquan", "last_name": "Hu", "name": null }, { "creator_type": "author", "first_name": "Qing", "last_name": "Gong", "name": null }, { "creator_type": "author", "first_name": "Dongxing", "last_name": "Zhu", "name": null }, { "creator_type": "author", "first_name": "Yiming", "last_name": "Xu", "name": null }, { "creator_type": "author", "first_name": "Rong", "last_name": "Liu", "name": null }, { "creator_type": "author", "first_name": "Lei", "last_name": "Liu", "name": null }, { "creator_type": "author", "first_name": "Cong", "last_name": "Yi", "name": null }, { "creator_type": "author", "first_name": "Yushan", "last_name": "Zhu", "name": null }, { "creator_type": "author", "first_name": "Ningfang", "last_name": "Ma", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Okamoto", "name": null }, { "creator_type": "author", "first_name": "Zhiping", "last_name": "Xie", "name": null }, { "creator_type": "author", "first_name": "Jinbao", "last_name": "Liu", "name": null }, { "creator_type": "author", "first_name": "Rong-Rong", "last_name": "He", "name": null }, { "creator_type": "author", "first_name": "Du", "last_name": "Feng", "name": null } ], "identifiers": { "doi": { "normalized": "10.7150/thno.49860" }, "pmcid": { "normalized": "PMC7681076" }, "pmid": { "normalized": "33391472" } }, "mesh": [ { "descriptor": "Autophagy", "descriptor_ui": "D001343", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Macroautophagy", "descriptor_ui": "D000080550", "major_topic": false }, { "descriptor": "Mitophagy", "descriptor_ui": "D063306", "major_topic": false }, { "descriptor": "Organelles", "descriptor_ui": "D015388", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021", "date_precision": "year", "issue": "1", "normalized_date": "2021", "pages": "222-256", "proceedings_title": null, "publisher": "", "title": "Theranostics", "volume": "11", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Selective autophagy of intracellular organelles: recent research advances.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Epidermal growth factor receptor (EGFR) exon 20 insertion mutations (Exon20ins) account for 4–12% of all EGFR mutations in non-small cell lung cancer (NSCLC) patients. Data on the differences in clinical characteristics between patients with Exon20ins and major mutations (M-mut) such as exon 19 deletion and L858R are limited. We retrospectively reviewed advanced NSCLC patients with EGFR mutations, who were treated with systemic therapy between January 2011 and December 2019. We identified 23 patients with Exon20ins and 534 patients with M-mut. In Exon20ins patients, the median age was 60 (range 27–88) years, and females and never-smokers were predominant. Clinical characteristics were similar in the two groups. In Exon20ins patients, 17 patients received platinum doublet as first-line therapy, and the overall response rate (ORR) and median progression-free survival (mPFS) were 11.8% and 8.9 months. Additionally, seven patients received conventional EGFR-tyrosine kinase inhibitors (TKIs), and eight patients anti-PD-1 antibodies in any-line therapy. ORR and mPFS of EGFR-TKIs and anti-PD-1 antibodies were 0%, 2.2 months and 25%, 3.1 months, respectively. Overall survival was significantly shorter in Exon20ins patients than in M-mut patients (29.3 vs. 43.4 months, p = 0.04). The clinical outcomes in Exon20ins patients were not satisfactory compared to M-mut patients.", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Chie", "last_name": "Morita", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Masayuki", "last_name": "Shirasawa", "name": null }, { "creator_type": "author", "first_name": "Ken", "last_name": "Masuda", "name": null }, { "creator_type": "author", "first_name": "Yuji", "last_name": "Matsumoto", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Shinno", "name": null }, { "creator_type": "author", "first_name": "Shigehiro", "last_name": "Yagishita", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Okuma", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Goto", "name": null }, { "creator_type": "author", "first_name": "Hidehito", "last_name": "Horinouchi", "name": null }, { "creator_type": "author", "first_name": "Noboru", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Noriko", "last_name": "Motoi", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null }, { "creator_type": "author", "first_name": "Yuichiro", "last_name": "Ohe", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41598-021-98275-3" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "34548567" } }, "mesh": [ { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Aged, 80 and over", "descriptor_ui": "D000369", "major_topic": false }, { "descriptor": "Carcinoma, Non-Small-Cell Lung", "descriptor_ui": "D002289", "major_topic": false }, { "descriptor": "ErbB Receptors", "descriptor_ui": "D066246", "major_topic": false }, { "descriptor": "Exons", "descriptor_ui": "D005091", "major_topic": true }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Lung Neoplasms", "descriptor_ui": "D008175", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Mutagenesis, Insertional", "descriptor_ui": "D016254", "major_topic": true }, { "descriptor": "Retrospective Studies", "descriptor_ui": "D012189", "major_topic": false }, { "descriptor": "Survival Analysis", "descriptor_ui": "D016019", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021", "date_precision": "year", "issue": "", "normalized_date": "2021", "pages": "", "proceedings_title": null, "publisher": "", "title": "Scientific Reports", "volume": "11", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Clinical characteristics of advanced non-small cell lung cancer patients with EGFR exon 20 insertions.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "A 50-year-old man demonstrated markedly increased number of white blood cells, anemia, severe splenomegaly, and bleeding tendency. Bone marrow analysis revealed remarkable hypercellularity; dysplasia in multilineage cells, including megakaryocytes; and fibrosis. He was eventually diagnosed with triple-negative myelofibrosis. A massive hematoma developed at the bone marrow biopsy site. A similar episode recurred after the second bone marrow biopsy. The von Willebrand factor and other coagulation factor activities were within normal ranges. Platelet aggregation analyses demonstrated highly impaired aggregation induced by ADP, collagen, and epinephrine. Treatment with hydroxyurea and ruxolitinib, a JAK inhibitor, was ineffective, and he eventually died on day 144 after hospitalization. Acquired platelet dysfunction uncommonly occurs in patients with myelodysplastic syndromes (MDS) and myeloproliferative neoplasms (MPN), without precise elucidation of the frequency and underlying mechanism. The onset of bleeding tendency in the current patient suggested that platelet dysfunction may be caused by somatic genetic events. Here, we discuss the mechanisms of acquired platelet dysfunction in MDS or MPN with a literature review.", "classifications": [ { "id": "Nishikii", "label": "Group Nishikii", "parent": "Shintaku", "type": "group" }, { "id": "Shintaku", "label": "Team Shintaku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Haruka", "last_name": "Momose", "name": null }, { "creator_type": "author", "first_name": "Hidekazu", "last_name": "Nishikii", "name": null }, { "creator_type": "author", "first_name": "Yukinori", "last_name": "Kozuma", "name": null }, { "creator_type": "author", "first_name": "Ikuyo", "last_name": "Ota-Tsutsumi", "name": null }, { "creator_type": "author", "first_name": "Yasuhito", "last_name": "Nannya", "name": null }, { "creator_type": "author", "first_name": "Chikashi", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Komeno", "name": null }, { "creator_type": "author", "first_name": "Manabu", "last_name": "Kusakabe", "name": null }, { "creator_type": "author", "first_name": "Yasuhisa", "last_name": "Yokoyama", "name": null }, { "creator_type": "author", "first_name": "Takayasu", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Naoki", "last_name": "Kurita", "name": null }, { "creator_type": "author", "first_name": "Ayano", "last_name": "Sootome", "name": null }, { "creator_type": "author", "first_name": "Mamiko", "last_name": "Sakata-Yanagimoto", "name": null }, { "creator_type": "author", "first_name": "Naoshi", "last_name": "Obara", "name": null }, { "creator_type": "author", "first_name": "Yuichi", "last_name": "Hasegawa", "name": null }, { "creator_type": "author", "first_name": "Seishi", "last_name": "Ogawa", "name": null }, { "creator_type": "author", "first_name": "Shigeru", "last_name": "Chiba", "name": null } ], "identifiers": { "doi": { "normalized": "10.11406/rinketsu.62.1406" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "34615801" } }, "mesh": [ { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Primary Myelofibrosis", "descriptor_ui": "D055728", "major_topic": true } ], "publication": { "conference_name": null, "date": "2021", "date_precision": "year", "issue": "9", "normalized_date": "2021", "pages": "1406-1411", "proceedings_title": null, "publisher": "", "title": "[Rinsho ketsueki] The Japanese journal of clinical hematology", "volume": "62", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "[Acquired platelet dysfunction with severe bleeding tendency in triple-negative myelofibrosis].", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "", "classifications": [ { "id": "Hamamoto", "label": "Group Hamamoto", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Ozawa", "name": null }, { "creator_type": "author", "first_name": "Syuzo", "last_name": "Kaneko", "name": null }, { "creator_type": "author", "first_name": "Frank", "last_name": "Szulzewsky", "name": null }, { "creator_type": "author", "first_name": "Zhiwei", "last_name": "Qiao", "name": null }, { "creator_type": "author", "first_name": "Mutsumi", "last_name": "Takadera", "name": null }, { "creator_type": "author", "first_name": "Yoshitaka", "last_name": "Narita", "name": null }, { "creator_type": "author", "first_name": "Tadashi", "last_name": "Kondo", "name": null }, { "creator_type": "author", "first_name": "Eric C.", "last_name": "Holland", "name": null }, { "creator_type": "author", "first_name": "Ryuji", "last_name": "Hamamoto", "name": null }, { "creator_type": "author", "first_name": "Koichi", "last_name": "Ichimura", "name": null } ], "identifiers": { "doi": { "normalized": "10.1186/s40478-021-01157-y" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "34044883" } }, "mesh": [], "publication": { "conference_name": null, "date": "2021", "date_precision": "year", "issue": "", "normalized_date": "2021", "pages": "", "proceedings_title": null, "publisher": "", "title": "Acta Neuropathologica Communications", "volume": "9", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Publisher Correction to: C11orf95-RELA fusion drives aberrant gene expression through the unique epigenetic regulation for ependymoma formation.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Erythropoietin (EPO) is a crucial hormone for erythropoiesis and produced by adult kidneys. Insufficient EPO production in chronic kidney disease (CKD) can cause renal anemia. Although hypoxia-inducible factors (HIFs) are known as a main regulator, the mechanisms of EPO production have not been fully elucidated. In this study, we aimed to examine the roles of retinoic acid (RA) in EPO production using EPO-producing cells derived from human induced pluripotent stem cells (hiPSC-EPO cells) that we previously established. RA augmented EPO production by hiPSC-EPO cells under hypoxia or by treatment with prolyl hydroxylase domain-containing protein (PHD) inhibitors that upregulate HIF signals. Combination treatment with RA and a PHD inhibitor improved renal anemia in vitamin A-depleted CKD model mice. Our findings using hiPSC-EPO cells and CKD model mice may contribute to clarifying the EPO production mechanism and developing efficient therapies for renal anemia.", "classifications": [ { "id": "Yamamoto", "label": "Group Yamamoto", "parent": "Toyoshima", "type": "group" }, { "id": "Toyoshima", "label": "Team Toyoshima", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Naoko", "last_name": "Katagiri", "name": null }, { "creator_type": "author", "first_name": "Hirofumi", "last_name": "Hitomi", "name": null }, { "creator_type": "author", "first_name": "Shin-Ichi", "last_name": "Mae", "name": null }, { "creator_type": "author", "first_name": "Maki", "last_name": "Kotaka", "name": null }, { "creator_type": "author", "first_name": "Li", "last_name": "Lei", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Akira", "last_name": "Nishiyama", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Osafune", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41598-021-83431-6" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "33594180" } }, "mesh": [ { "descriptor": "Anemia", "descriptor_ui": "D000740", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Basic Helix-Loop-Helix Proteins", "descriptor_ui": "D051792", "major_topic": false }, { "descriptor": "Drug Evaluation, Preclinical", "descriptor_ui": "D004353", "major_topic": false }, { "descriptor": "Drug Therapy, Combination", "descriptor_ui": "D004359", "major_topic": false }, { "descriptor": "Endothelial PAS Domain-Containing Protein 1", "descriptor_ui": "D000099162", "major_topic": false }, { "descriptor": "Erythropoietin", "descriptor_ui": "D004921", "major_topic": false }, { "descriptor": "Glycine", "descriptor_ui": "D005998", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Hypoxia-Inducible Factor 1, alpha Subunit", "descriptor_ui": "D051795", "major_topic": false }, { "descriptor": "Hypoxia-Inducible Factor-Proline Dioxygenases", "descriptor_ui": "D064799", "major_topic": false }, { "descriptor": "Induced Pluripotent Stem Cells", "descriptor_ui": "D057026", "major_topic": false }, { "descriptor": "Isoquinolines", "descriptor_ui": "D007546", "major_topic": false }, { "descriptor": "Kidney Diseases", "descriptor_ui": "D007674", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Tretinoin", "descriptor_ui": "D014212", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021", "date_precision": "year", "issue": "", "normalized_date": "2021", "pages": "", "proceedings_title": null, "publisher": "", "title": "Scientific Reports", "volume": "11", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Retinoic acid regulates erythropoietin production cooperatively with hypoxia-inducible factors in human iPSC-derived erythropoietin-producing cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Age is a major risk factor for COVID-19 severity, and T cells play a central role in anti-SARS-CoV-2 immunity. Because SARS-CoV-2-cross-reactive T cells have been detected in unexposed individuals, we investigated the age-related differences in pre-existing SARS-CoV-2-reactive T cells. SARS-CoV-2-reactive CD4(+) T cells from young and elderly individuals were mainly detected in the central memory fraction and exhibited similar functionalities and numbers. Naive-phenotype SARS-CoV-2-reactive CD8(+) T cell populations decreased markedly in the elderly, while those with terminally differentiated and senescent phenotypes increased. Furthermore, senescent SARS-CoV-2-reactive CD8(+) T cell populations were higher in cytomegalovirus seropositive young individuals compared to seronegative ones. Our findings suggest that age-related differences in pre-existing SARS-CoV-2-reactive CD8(+) T cells may explain the poor outcomes in elderly patients and that cytomegalovirus infection is a potential factor affecting CD8(+) T cell immunity against SARS-CoV-2. Thus, this study provides insights for developing effective therapeutic and vaccination strategies for the elderly.", "classifications": [ { "id": "Yamamoto", "label": "Group Yamamoto", "parent": "Toyoshima", "type": "group" }, { "id": "Toyoshima", "label": "Team Toyoshima", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Norihide", "last_name": "Jo", "name": null }, { "creator_type": "author", "first_name": "Rui", "last_name": "Zhang", "name": null }, { "creator_type": "author", "first_name": "Hideki", "last_name": "Ueno", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Daniela", "last_name": "Weiskopf", "name": null }, { "creator_type": "author", "first_name": "Miki", "last_name": "Nagao", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Yamanaka", "name": null }, { "creator_type": "author", "first_name": "Yoko", "last_name": "Hamazaki", "name": null } ], "identifiers": { "doi": { "normalized": "10.3389/fragi.2021.719342" }, "pmcid": { "normalized": "PMC9261342" }, "pmid": { "normalized": "35822004" } }, "mesh": [], "publication": { "conference_name": null, "date": "2021", "date_precision": "year", "issue": "", "normalized_date": "2021", "pages": "719342", "proceedings_title": null, "publisher": "", "title": "Frontiers in aging", "volume": "2", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Aging and CMV Infection Affect Pre-existing SARS-CoV-2-Reactive CD8(+) T Cells in Unexposed Individuals.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The newly emerged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is causing a spread of coronavirus disease 2019 (COVID-19) globally. In order to end the COVID-19 pandemic, an effective vaccine against SARS-CoV-2 must be produced at low cost and disseminated worldwide. The spike (S) protein of coronaviruses plays a pivotal role in the infection to host cells. Therefore, targeting the S protein is one of the most rational approaches in developing vaccines and therapeutic agents. In this study, we optimized the expression of secreted trimerized S protein of SARS-CoV-2 using a silkworm-baculovirus expression vector system and evaluated its immunogenicity in mice. The results showed that the S protein forming the trimeric structure was the most stable when the chicken cartilage matrix protein was used as the trimeric motif and could be purified in large amounts from the serum of silkworm larvae. The purified S protein efficiently induced antigen-specific antibodies in mouse serum without adjuvant, but its ability to induce neutralizing antibodies was low. After examining several adjuvants, the use of Alum adjuvant was the most effective in inducing strong neutralizing antibody induction. We also examined the adjuvant effect of paramylon from Euglena gracilis when administered with the S protein. Our results highlight the effectiveness and suitable construct design of the S protein produced in silkworms for the subunit vaccine development against SARS-CoV-2.", "classifications": [ { "id": "Nishida", "label": "Group Nishida", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Akitsu", "last_name": "Masuda", "name": null }, { "creator_type": "author", "first_name": "Jae Man", "last_name": "Lee", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Miyata", "name": null }, { "creator_type": "author", "first_name": "Hiroaki", "last_name": "Mon", "name": null }, { "creator_type": "author", "first_name": "Keita", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Kosuke", "last_name": "Oyama", "name": null }, { "creator_type": "author", "first_name": "Yasuteru", "last_name": "Sakurai", "name": null }, { "creator_type": "author", "first_name": "Jiro", "last_name": "Yasuda", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Tadashi", "last_name": "Ueda", "name": null }, { "creator_type": "author", "first_name": "Yuri", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Motohiro", "last_name": "Nishida", "name": null }, { "creator_type": "author", "first_name": "Noriko", "last_name": "Karasaki", "name": null }, { "creator_type": "author", "first_name": "Kohei", "last_name": "Kakino", "name": null }, { "creator_type": "author", "first_name": "Takeru", "last_name": "Ebihara", "name": null }, { "creator_type": "author", "first_name": "Takumi", "last_name": "Nagasato", "name": null }, { "creator_type": "author", "first_name": "Masato", "last_name": "Hino", "name": null }, { "creator_type": "author", "first_name": "Ayaka", "last_name": "Nakashima", "name": null }, { "creator_type": "author", "first_name": "Kengo", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Yoshino", "last_name": "Tonooka", "name": null }, { "creator_type": "author", "first_name": "Miyu", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Takato", "last_name": "Moriyama", "name": null }, { "creator_type": "author", "first_name": "Hirokazu", "last_name": "Nakatake", "name": null }, { "creator_type": "author", "first_name": "Ryosuke", "last_name": "Fujita", "name": null }, { "creator_type": "author", "first_name": "Takahiro", "last_name": "Kusakabe", "name": null } ], "identifiers": { "doi": { "normalized": "10.3389/fimmu.2021.803647" }, "pmcid": { "normalized": "PMC8789674" }, "pmid": { "normalized": "35095889" } }, "mesh": [ { "descriptor": "Adjuvants, Immunologic", "descriptor_ui": "D000276", "major_topic": false }, { "descriptor": "Alum Compounds", "descriptor_ui": "D000534", "major_topic": false }, { "descriptor": "Aluminum Hydroxide", "descriptor_ui": "D000536", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Antibodies, Neutralizing", "descriptor_ui": "D057134", "major_topic": false }, { "descriptor": "Antibodies, Viral", "descriptor_ui": "D000914", "major_topic": false }, { "descriptor": "Bombyx", "descriptor_ui": "D012831", "major_topic": false }, { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "Chickens", "descriptor_ui": "D002645", "major_topic": false }, { "descriptor": "Chlorocebus aethiops", "descriptor_ui": "D002522", "major_topic": false }, { "descriptor": "COVID-19", "descriptor_ui": "D000086382", "major_topic": false }, { "descriptor": "COVID-19 Vaccines", "descriptor_ui": "D000086663", "major_topic": false }, { "descriptor": "Euglena gracilis", "descriptor_ui": "D005056", "major_topic": false }, { "descriptor": "Euglenozoa Infections", "descriptor_ui": "D056986", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred BALB C", "descriptor_ui": "D008807", "major_topic": false }, { "descriptor": "Pandemics", "descriptor_ui": "D058873", "major_topic": false }, { "descriptor": "SARS-CoV-2", "descriptor_ui": "D000086402", "major_topic": false }, { "descriptor": "Spike Glycoprotein, Coronavirus", "descriptor_ui": "D064370", "major_topic": false }, { "descriptor": "Vaccination", "descriptor_ui": "D014611", "major_topic": false }, { "descriptor": "Vero Cells", "descriptor_ui": "D014709", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021", "date_precision": "year", "issue": "", "normalized_date": "2021", "pages": "803647", "proceedings_title": null, "publisher": "", "title": "Frontiers in immunology", "volume": "12", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Optimization of SARS-CoV-2 Spike Protein Expression in the Silkworm and Induction of Efficient Protective Immunity by Inoculation With Alum Adjuvants.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "PURPOSE: To evaluate the diagnostic yield, safety, and factors associated with the diagnostic yield of percutaneous core needle biopsy (PNB) for peritoneal/omental lesions. METHODS: Consecutive 297 patients (67 men, 230 women; median age, 64 years [range 15-87]) who underwent a PNB for 311 peritoneal/omental lesions at a single center from April 2010 to March 2020 were evaluated retrospectively. The preprocedural CT findings, diagnostic yield, sensitivity, specificity, PPV, NPV, technical success rate, and adverse events were analyzed. Surgical or clinical diagnosis with follow-up was the diagnostic reference standard. Adverse events were evaluated using the Society of Interventional Radiology guidelines. RESULTS: The median anteroposterior (AP) diameter and CT value of the target lesion were 24 mm (range 5-78) and 46 HU (range - 75 to 140), respectively. Ascites was interposed on the puncture route in 106 patients (34.1%). The technical success rate was 100%. The diagnostic yield, sensitivity, specificity, PPV, and NPV were 93.9%, 93.8%, 100%, 100%, and 20.8%, respectively. Minor complications were observed following five procedures (1.6%). The diagnostic yield was lower for fat-dominant lesions than for other lesions (82.6% vs. 95.8%, p = 0.002). The diagnostic PNB group had a greater AP diameter than did the non-diagnostic PNB group (27.3 +/- 13.0 vs. 20.7 +/- 8.4 mm, p = 0.037). CONCLUSION: PNB for peritoneal/omental lesions provided a sufficiently high diagnostic yield and minimal adverse events. Lesions with a greater AP diameter and a higher density on CT would provide more diagnostic specimens from this technique.", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Shunsuke", "last_name": "Sugawara", "name": null }, { "creator_type": "author", "first_name": "Miyuki", "last_name": "Sone", "name": null }, { "creator_type": "author", "first_name": "Chihiro", "last_name": "Itou", "name": null }, { "creator_type": "author", "first_name": "Shintaro", "last_name": "Kimura", "name": null }, { "creator_type": "author", "first_name": "Masahiko", "last_name": "Kusumoto", "name": null }, { "creator_type": "author", "first_name": "Tomoyasu", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Kan", "last_name": "Yonemori", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null }, { "creator_type": "author", "first_name": "Yasuaki", "last_name": "Arai", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/s00261-021-03088-7" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "34047802" } }, "mesh": [ { "descriptor": "Adolescent", "descriptor_ui": "D000293", "major_topic": false }, { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Aged, 80 and over", "descriptor_ui": "D000369", "major_topic": false }, { "descriptor": "Biopsy, Large-Core Needle", "descriptor_ui": "D062005", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Image-Guided Biopsy", "descriptor_ui": "D061705", "major_topic": true }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Omentum", "descriptor_ui": "D009852", "major_topic": false }, { "descriptor": "Peritoneal Diseases", "descriptor_ui": "D010532", "major_topic": true }, { "descriptor": "Radiography, Interventional", "descriptor_ui": "D015641", "major_topic": false }, { "descriptor": "Retrospective Studies", "descriptor_ui": "D012189", "major_topic": false }, { "descriptor": "Sensitivity and Specificity", "descriptor_ui": "D012680", "major_topic": false }, { "descriptor": "Young Adult", "descriptor_ui": "D055815", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Sep", "date_precision": "unknown", "issue": "9", "normalized_date": null, "pages": "4499-4508", "proceedings_title": null, "publisher": "", "title": "Abdominal radiology (New York)", "volume": "46", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Analysis of factors affecting the diagnostic yield of image-guided percutaneous core needle biopsy for peritoneal/omental lesions.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: Chronic itch is a debilitating symptom of inflammatory skin diseases, but the underlying mechanism is poorly understood. We have recently demonstrated that astrocytes in the spinal dorsal horn become reactive in models of atopic and contact dermatitis via activation of the transcription factor signal transducer and activator of transcription 3 (STAT3) and critically contribute to chronic itch. In general, STAT3 is transiently activated; however, STAT3 activation in reactive astrocytes of chronic itch model mice persistently occurs via an unknown mechanism. OBJECTIVE: We aimed to determine the mechanisms of persistent activation of astrocytic STAT3 in chronic itch conditions. METHODS: To determine the factors that are required for persistent activation of astrocytic STAT3, Western blotting and calcium imaging with cultured astrocytes or spinal cord slices were performed. Thereafter, chronic itch model mice were used for genetic and behavioral experiments to confirm the role of the factors determined to mediate persistent STAT3 activation from in vitro and ex vivo experiments in chronic itch. RESULTS: IP3 receptor type 1 (IP3R1) knockdown in astrocytes suppressed IL-6-induced persistent STAT3 activation and expression of lipocalin-2 (LCN2), an astrocytic STAT3-dependent inflammatory factor that is required for chronic itch. IP3R1-dependent astrocytic Ca(2+) responses involved Ca(2+) influx through the cation channel transient receptor potential canonical (TRPC), which was required for persistent STAT3 activation evoked by IL-6. IL-6 expression was upregulated in dorsal root ganglion neurons in a mouse model of chronic itch. Dorsal root ganglion neuron-specific IL-6 knockdown, spinal astrocyte-specific IP3R1 knockdown, and pharmacologic spinal TRPC inhibition attenuated LCN2 expression and chronic itch. CONCLUSION: Our findings suggest that IP3R1/TRPC channel-mediated Ca(2+) signals elicited by IL-6 in astrocytes are necessary for persistent STAT3 activation, LCN2 expression, and chronic itch, and they may also provide new targets for therapeutic intervention.", "classifications": [ { "id": "Nishida", "label": "Group Nishida", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Miho", "last_name": "Shiratori-Hayashi", "name": null }, { "creator_type": "author", "first_name": "Chiharu", "last_name": "Yamaguchi", "name": null }, { "creator_type": "author", "first_name": "Kazushi", "last_name": "Eguchi", "name": null }, { "creator_type": "author", "first_name": "Yuto", "last_name": "Shiraishi", "name": null }, { "creator_type": "author", "first_name": "Keita", "last_name": "Kohno", "name": null }, { "creator_type": "author", "first_name": "Katsuhiko", "last_name": "Mikoshiba", "name": null }, { "creator_type": "author", "first_name": "Kazuhide", "last_name": "Inoue", "name": null }, { "creator_type": "author", "first_name": "Motohiro", "last_name": "Nishida", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Tsuda", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.jaci.2020.06.039" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "32781002" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Astrocytes", "descriptor_ui": "D001253", "major_topic": false }, { "descriptor": "Calcium Signaling", "descriptor_ui": "D020013", "major_topic": false }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Chronic Disease", "descriptor_ui": "D002908", "major_topic": false }, { "descriptor": "Ganglia, Spinal", "descriptor_ui": "D005727", "major_topic": false }, { "descriptor": "Inositol 1,4,5-Trisphosphate Receptors", "descriptor_ui": "D053496", "major_topic": false }, { "descriptor": "Interleukin-6", "descriptor_ui": "D015850", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Pruritus", "descriptor_ui": "D011537", "major_topic": false }, { "descriptor": "STAT3 Transcription Factor", "descriptor_ui": "D050796", "major_topic": false }, { "descriptor": "TRPC Cation Channels", "descriptor_ui": "D050052", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Apr", "date_precision": "unknown", "issue": "4", "normalized_date": null, "pages": "1341-1353", "proceedings_title": null, "publisher": "", "title": "The Journal of allergy and clinical immunology", "volume": "147", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Astrocytic STAT3 activation and chronic itch require IP3R1/TRPC-dependent Ca(2+) signals in mice.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Introduction: Diagnostic testing is important in determining appropriate treatment for individuals with lung cancer. In 2018, testing of five biomarkers (EGFR, ALK, ROS1, BRAF, programmed cell death-ligand 1 [PD-L1]) was approved in Japan. Information is lacking regarding real-world testing patterns. Methods: This descriptive, retrospective observational study used the Japan Medical Data Vision Co., Ltd. (MDV), database (June 2017–November 2018) and covered data for EGFR, ALK, ROS1, and PD-L1; records on BRAF testing were not yet available. Adults diagnosed with having lung cancer (International Classification of Diseases-10 C34) with record of any biomarker test ordered were included. Results: Of 8323 patients with any biomarker test, 83.2% were tested for EGFR, 55.3% for ALK, 32.2% ROS1, and 77.2% PD-L1. Combinations of EGFR with other biomarkers accounted for approximately 80% of the testing patterns; 1427 patients (17.1%) had combination testing ordered for EGFR/ALK/ROS1/PD-L1, but some biomarker combinations were tested in less than 1% of the cases. Median time from first testing order to treatment order was 22 (range: 2–525) days overall and increased with number of testing instances: 21 (2–509) days for patients with one, 28 (3–525) days for patients with two, and 30 (9–502) days for patients with three. A 7-day pattern of peaks was observed in the test order date and time to treatment. Conclusions: This real-world evidence revealed variations in diagnostic testing patterns, which could affect time to treatment in Japan. Variations are likely influenced by individual biomarker prioritization considering limited tissue samples in clinical practice.", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null }, { "creator_type": "author", "first_name": "Yasumasa", "last_name": "Yoshiki", "name": null }, { "creator_type": "author", "first_name": "Koichi", "last_name": "Matsumura", "name": null }, { "creator_type": "author", "first_name": "Kanae", "last_name": "Togo", "name": null }, { "creator_type": "author", "first_name": "Hironori", "last_name": "Kikkawa", "name": null }, { "creator_type": "author", "first_name": "Laura", "last_name": "Iadeluca", "name": null }, { "creator_type": "author", "first_name": "Benjamin", "last_name": "Li", "name": null }, { "creator_type": "author", "first_name": "Kazuto", "last_name": "Nishio", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.jtocrr.2020.100136" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "34589999" } }, "mesh": [], "publication": { "conference_name": null, "date": "2021 Mar", "date_precision": "unknown", "issue": "3", "normalized_date": null, "pages": "", "proceedings_title": null, "publisher": "", "title": "JTO Clinical and Research Reports", "volume": "2", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Real-World Evidence of Diagnostic Testing for Driver Oncogene Mutations in Lung Cancer in Japan.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Dozens of histone methyltransferases have been identified and biochemically characterized, but the pathological roles of their dysfunction in human diseases such as cancer remain largely unclear. Here, we demonstrate the involvement of EHMT1, a histone lysine methyltransferase, in lung cancer. Immunohistochemical analysis indicated that the expression levels of EHMT1 are significantly elevated in human lung carcinomas compared with non‐neoplastic lung tissues. Through gene ontology analysis of RNA‐seq results, we showed that EHMT1 is clearly associated with apoptosis and the cell cycle process. Moreover, FACS analysis and cell growth assays showed that knockdown of EHMT1 induced apoptosis and G1 cell cycle arrest via upregulation of CDKN1A in A549 and H1299 cell lines. Finally, in 3D spheroid culture, compared to control cells, EHMT1 knockdown cells exhibited reduced aggregation of 3D spheroids and clear upregulation of CDKN1A and downregulation of E‐cadherin. Therefore, the results of the present study suggest that EHMT1 plays a critical role in the regulation of cancer cell apoptosis and the cell cycle by modulating CDKN1A expression. Further functional analyses of EHMT1 in the context of human tumorigenesis may aid in the development of novel therapeutic strategies for cancer.", "classifications": [ { "id": "Hamamoto", "label": "Group Hamamoto", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Jinkwon", "last_name": "Lee", "name": null }, { "creator_type": "author", "first_name": "Kwangho", "last_name": "Kim", "name": null }, { "creator_type": "author", "first_name": "Tae Young", "last_name": "Ryu", "name": null }, { "creator_type": "author", "first_name": "Cho-Rok", "last_name": "Jung", "name": null }, { "creator_type": "author", "first_name": "Moo-Seung", "last_name": "Lee", "name": null }, { "creator_type": "author", "first_name": "Jung Hwa", "last_name": "Lim", "name": null }, { "creator_type": "author", "first_name": "Kunhyang", "last_name": "Park", "name": null }, { "creator_type": "author", "first_name": "Dae-Soo", "last_name": "Kim", "name": null }, { "creator_type": "author", "first_name": "Mi-Young", "last_name": "Son", "name": null }, { "creator_type": "author", "first_name": "Ryuji", "last_name": "Hamamoto", "name": null }, { "creator_type": "author", "first_name": "Hyun-Soo", "last_name": "Cho", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/1878-0261.13050" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "34214254" } }, "mesh": [ { "descriptor": "Apoptosis", "descriptor_ui": "D017209", "major_topic": false }, { "descriptor": "Cell Cycle", "descriptor_ui": "D002453", "major_topic": false }, { "descriptor": "Cell Cycle Checkpoints", "descriptor_ui": "D059447", "major_topic": false }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Cell Proliferation", "descriptor_ui": "D049109", "major_topic": false }, { "descriptor": "Cyclin-Dependent Kinase Inhibitor p21", "descriptor_ui": "D050759", "major_topic": false }, { "descriptor": "Gene Expression Regulation, Neoplastic", "descriptor_ui": "D015972", "major_topic": false }, { "descriptor": "Histone-Lysine N-Methyltransferase", "descriptor_ui": "D011495", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Lung", "descriptor_ui": "D008168", "major_topic": false }, { "descriptor": "Lung Neoplasms", "descriptor_ui": "D008175", "major_topic": true } ], "publication": { "conference_name": null, "date": "2021 Nov", "date_precision": "unknown", "issue": "11", "normalized_date": null, "pages": "2989-3002", "proceedings_title": null, "publisher": "", "title": "Molecular Oncology", "volume": "15", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "EHMT1 knockdown induces apoptosis and cell cycle arrest in lung cancer cells by increasing CDKN1A expression.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Alternative mRNA isoforms play a key role in generating diverse protein isoforms. To dissect isoform usage in the subcellular compartments of single cells, we introduced an novel approach, nanopore sequencing coupled with single-cell integrated nuclear and cytoplasmic RNA sequencing, that couples microfluidic fractionation, which separates cytoplasmic RNA from nuclear RNA, with full-length complementary DNA (cDNA) sequencing using a nanopore sequencer. Leveraging full-length cDNA reads, we found that the nuclear transcripts are notably more diverse than cytoplasmic transcripts. Our findings also indicated that transcriptional noise emanating from the nucleus is regulated across the nuclear membrane and then either attenuated or amplified in the cytoplasm depending on the function involved. Overall, our results provide the landscape that shows how the transcriptional noise arising from the nucleus propagates to the cytoplasm.", "classifications": [ { "id": "Shintaku", "label": "Group Shintaku", "parent": "Shintaku", "type": "group" }, { "id": "Shintaku", "label": "Team Shintaku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yusuke", "last_name": "Oguchi", "name": null }, { "creator_type": "author", "first_name": "Yuka", "last_name": "Ozaki", "name": null }, { "creator_type": "author", "first_name": "Mahmoud N.", "last_name": "Abdelmoez", "name": null }, { "creator_type": "author", "first_name": "Hirofumi", "last_name": "Shintaku", "name": null } ], "identifiers": { "doi": { "normalized": "10.1126/sciadv.abe0317" }, "pmcid": { "normalized": "PMC8026137" }, "pmid": { "normalized": "33827812" } }, "mesh": [], "publication": { "conference_name": null, "date": "2021 Apr", "date_precision": "unknown", "issue": "15", "normalized_date": null, "pages": "eabe0317", "proceedings_title": null, "publisher": "", "title": "Science advances", "volume": "7", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "NanoSINC-seq dissects the isoform diversity in subcellular compartments of single cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Background: Nivolumab and pembrolizumab are promising therapies for gastric adenocarcinoma. The 22C3 and 28-8 pharmDx immunohistochemistry assays for programmed death ligand-1 scoring criteria have been developed. This study compared the programmed death ligand-1 staining patterns of gastric adenocarcinoma evaluated by the 22C3 and 28-8 pharmDx assays. Methods: Tissue microarray analysis was performed for 226 patients with gastric adenocarcinoma who underwent curative surgery. Interobserver concordance between the 22C3 and 28-8 pharmDx assays was assessed to compare the dichotomized expression values. Programmed death ligand-1 positivity was assessed by combined positive score and tumor proportion score. Immunohistochemistry for deficient mismatch repair proteins and Epstein-Barr virus-encoded RNA in situ hybridization was examined. Results: Programmed death ligand-1 positivity with a combined positive score ≥5 was detected in 63 patients (28%) by the 22C3 pharmDx assay, and in 45 patients (20%) by the 28-8 pharmDx assay. A pairwise comparison of the 22C3 and 28-8 pharmDx assays showed 87% of pairs were concordant and 11% higher expressions for the 22C3 pharmDx assay, with strong concordance (kappa score =0.881 with a combined positive score cutoff of 5). The programmed death ligand-1 positivity rate (range, 3–5%) of the tumor proportion score was markedly lower than that of the combined positive score in the two assays. Programmed death ligand-1 positivity of the combined positive score in these two assays was associated with mismatch repair proteins and Epstein-Barr virus status. There was no significant difference in the overall survival between programmed death ligand-1, mismatch repair proteins, and Epstein-Barr virus status. Conclusions: The study findings suggest the potential interchangeability of the 22C3 and 28-8 pharmDx assays to determine programmed death ligand-1 expression levels in gastric adenocarcinoma patients.", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yukiya", "last_name": "Narita", "name": null }, { "creator_type": "author", "first_name": "Eiichi", "last_name": "Sasaki", "name": null }, { "creator_type": "author", "first_name": "Toshiki", "last_name": "Masuishi", "name": null }, { "creator_type": "author", "first_name": "Hiroya", "last_name": "Taniguchi", "name": null }, { "creator_type": "author", "first_name": "Shigenori", "last_name": "Kadowaki", "name": null }, { "creator_type": "author", "first_name": "Seiji", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null }, { "creator_type": "author", "first_name": "Kei", "last_name": "Muro", "name": null } ], "identifiers": { "doi": { "normalized": "10.21037/jgo-21-505" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "35070399" } }, "mesh": [], "publication": { "conference_name": null, "date": "2021 Dec", "date_precision": "unknown", "issue": "6", "normalized_date": null, "pages": "2696-2705", "proceedings_title": null, "publisher": "", "title": "Journal of Gastrointestinal Oncology", "volume": "12", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "PD-L1 immunohistochemistry comparison of 22C3 and 28-8 assays for gastric cancer.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Simple Summary: Formalin-fixed paraffin-embedded (FFPE) specimens, which are pathological specimens of human tissues, are of high clinical value because they are associated with clinical information such as drug sensitivity and side effects and exist in huge numbers worldwide. However, the quality of DNA and RNA extracted from FFPE specimens is generally poor, and it is still difficult to perform ChIP-seq. Here, we describe an experimental procedure for FFPE ChIP-seq called RCRA ChIP-seq that allows identification of the genome-wide distributions of key histone modifications and binding sites of the insulator transcription factor CTCF. We have also succeeded in obtaining accurate and stable results even for the analysis of a large number of FFPE samples by using an industrial robot. Thus, routine ChIP-seq analysis of FFPE specimens could lead to new epigenomic mechanisms in various diseases. Abstract: Although chromatin immunoprecipitation and next-generation sequencing (ChIP-seq) using formalin-fixed paraffin-embedded tissue (FFPE) has been reported, it remained elusive whether they retained accurate transcription factor binding. Here, we developed a method to identify the binding sites of the insulator transcription factor CTCF and the genome-wide distribution of histone modifications involved in transcriptional activation. Importantly, we provide evidence that the ChIP-seq datasets obtained from FFPE samples are similar to or even better than the data for corresponding fresh-frozen samples, indicating that FFPE samples are compatible with ChIP-seq analysis. H3K27ac ChIP-seq analyses of 69 FFPE samples using a dual-arm robot revealed that driver mutations in EGFR were distinguishable from pan-negative cases and were relatively homogeneous as a group in lung adenocarcinomas. Thus, our results demonstrate that FFPE samples are an important source for epigenomic research, enabling the study of histone modifications, nuclear chromatin structure, and clinical data.", "classifications": [ { "id": "Hamamoto", "label": "Group Hamamoto", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Syuzo", "last_name": "Kaneko", "name": null }, { "creator_type": "author", "first_name": "Toutai", "last_name": "Mitsuyama", "name": null }, { "creator_type": "author", "first_name": "Kouya", "last_name": "Shiraishi", "name": null }, { "creator_type": "author", "first_name": "Noriko", "last_name": "Ikawa", "name": null }, { "creator_type": "author", "first_name": "Kanto", "last_name": "Shozu", "name": null }, { "creator_type": "author", "first_name": "Ai", "last_name": "Dozen", "name": null }, { "creator_type": "author", "first_name": "Hidenori", "last_name": "Machino", "name": null }, { "creator_type": "author", "first_name": "Ken", "last_name": "Asada", "name": null }, { "creator_type": "author", "first_name": "Masaaki", "last_name": "Komatsu", "name": null }, { "creator_type": "author", "first_name": "Asako", "last_name": "Kukita", "name": null }, { "creator_type": "author", "first_name": "Kenbun", "last_name": "Sone", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Noriko", "last_name": "Motoi", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Hayami", "name": null }, { "creator_type": "author", "first_name": "Yutaka", "last_name": "Yoneoka", "name": null }, { "creator_type": "author", "first_name": "Tomoyasu", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Kohno", "name": null }, { "creator_type": "author", "first_name": "Toru", "last_name": "Natsume", "name": null }, { "creator_type": "author", "first_name": "Gottfried", "last_name": "von Keudell", "name": null }, { "creator_type": "author", "first_name": "Vassiliki", "last_name": "Saloura", "name": null }, { "creator_type": "author", "first_name": "Hiroki", "last_name": "Yamaue", "name": null }, { "creator_type": "author", "first_name": "Ryuji", "last_name": "Hamamoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.3390/cancers13092126" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "33924956" } }, "mesh": [], "publication": { "conference_name": null, "date": "2021 May", "date_precision": "unknown", "issue": "9", "normalized_date": null, "pages": "", "proceedings_title": null, "publisher": "", "title": "Cancers", "volume": "13", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Genome-Wide Chromatin Analysis of FFPE Tissues Using a Dual-Arm Robot with Clinical Potential.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "", "classifications": [ { "id": "Onami", "label": "Group Onami", "parent": "Fujiwara", "type": "group" }, { "id": "Fujiwara", "label": "Team Fujiwara", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Ugis", "last_name": "Sarkans", "name": null }, { "creator_type": "author", "first_name": "Wah", "last_name": "Chiu", "name": null }, { "creator_type": "author", "first_name": "Lucy", "last_name": "Collinson", "name": null }, { "creator_type": "author", "first_name": "Michele C.", "last_name": "Darrow", "name": null }, { "creator_type": "author", "first_name": "Jan", "last_name": "Ellenberg", "name": null }, { "creator_type": "author", "first_name": "David", "last_name": "Grunwald", "name": null }, { "creator_type": "author", "first_name": "Jean-Karim", "last_name": "Heriche", "name": null }, { "creator_type": "author", "first_name": "Andrii", "last_name": "Iudin", "name": null }, { "creator_type": "author", "first_name": "Gabriel G.", "last_name": "Martins", "name": null }, { "creator_type": "author", "first_name": "Terry", "last_name": "Meehan", "name": null }, { "creator_type": "author", "first_name": "Kedar", "last_name": "Narayan", "name": null }, { "creator_type": "author", "first_name": "Ardan", "last_name": "Patwardhan", "name": null }, { "creator_type": "author", "first_name": "Matthew Robert Geoffrey", "last_name": "Russell", "name": null }, { "creator_type": "author", "first_name": "Helen R.", "last_name": "Saibil", "name": null }, { "creator_type": "author", "first_name": "Caterina", "last_name": "Strambio-De-Castillia", "name": null }, { "creator_type": "author", "first_name": "Jason R.", "last_name": "Swedlow", "name": null }, { "creator_type": "author", "first_name": "Christian", "last_name": "Tischer", "name": null }, { "creator_type": "author", "first_name": "Virginie", "last_name": "Uhlmann", "name": null }, { "creator_type": "author", "first_name": "Paul", "last_name": "Verkade", "name": null }, { "creator_type": "author", "first_name": "Mary", "last_name": "Barlow", "name": null }, { "creator_type": "author", "first_name": "Omer", "last_name": "Bayraktar", "name": null }, { "creator_type": "author", "first_name": "Ewan", "last_name": "Birney", "name": null }, { "creator_type": "author", "first_name": "Cesare", "last_name": "Catavitello", "name": null }, { "creator_type": "author", "first_name": "Christopher", "last_name": "Cawthorne", "name": null }, { "creator_type": "author", "first_name": "Stephan", "last_name": "Wagner-Conrad", "name": null }, { "creator_type": "author", "first_name": "Elizabeth", "last_name": "Duke", "name": null }, { "creator_type": "author", "first_name": "Perrine", "last_name": "Paul-Gilloteaux", "name": null }, { "creator_type": "author", "first_name": "Emmanuel", "last_name": "Gustin", "name": null }, { "creator_type": "author", "first_name": "Maria", "last_name": "Harkiolaki", "name": null }, { "creator_type": "author", "first_name": "Pasi", "last_name": "Kankaanpaa", "name": null }, { "creator_type": "author", "first_name": "Thomas", "last_name": "Lemberger", "name": null }, { "creator_type": "author", "first_name": "Jo", "last_name": "McEntyre", "name": null }, { "creator_type": "author", "first_name": "Josh", "last_name": "Moore", "name": null }, { "creator_type": "author", "first_name": "Andrew W.", "last_name": "Nicholls", "name": null }, { "creator_type": "author", "first_name": "Shuichi", "last_name": "Onami", "name": null }, { "creator_type": "author", "first_name": "Helen", "last_name": "Parkinson", "name": null }, { "creator_type": "author", "first_name": "Maddy", "last_name": "Parsons", "name": null }, { "creator_type": "author", "first_name": "Marina", "last_name": "Romanchikova", "name": null }, { "creator_type": "author", "first_name": "Nicholas", "last_name": "Sofroniew", "name": null }, { "creator_type": "author", "first_name": "Jim", "last_name": "Swoger", "name": null }, { "creator_type": "author", "first_name": "Nadine", "last_name": "Utz", "name": null }, { "creator_type": "author", "first_name": "Lenard M.", "last_name": "Voortman", "name": null }, { "creator_type": "author", "first_name": "Frances", "last_name": "Wong", "name": null }, { "creator_type": "author", "first_name": "Peijun", "last_name": "Zhang", "name": null }, { "creator_type": "author", "first_name": "Gerard J.", "last_name": "Kleywegt", "name": null }, { "creator_type": "author", "first_name": "Alvis", "last_name": "Brazma", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41592-021-01166-8" }, "pmcid": { "normalized": "PMC8606015" }, "pmid": { "normalized": "34021280" } }, "mesh": [ { "descriptor": "Algorithms", "descriptor_ui": "D000465", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Computational Biology", "descriptor_ui": "D019295", "major_topic": false }, { "descriptor": "Congresses as Topic", "descriptor_ui": "D003226", "major_topic": false }, { "descriptor": "Cryoelectron Microscopy", "descriptor_ui": "D020285", "major_topic": false }, { "descriptor": "Data Mining", "descriptor_ui": "D057225", "major_topic": false }, { "descriptor": "Databases, Factual", "descriptor_ui": "D016208", "major_topic": false }, { "descriptor": "Diagnostic Imaging", "descriptor_ui": "D003952", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Image Processing, Computer-Assisted", "descriptor_ui": "D007091", "major_topic": false }, { "descriptor": "Metadata", "descriptor_ui": "D000071253", "major_topic": true }, { "descriptor": "Microscopy", "descriptor_ui": "D008853", "major_topic": false }, { "descriptor": "Software", "descriptor_ui": "D012984", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Dec", "date_precision": "unknown", "issue": "12", "normalized_date": null, "pages": "1418-1422", "proceedings_title": null, "publisher": "", "title": "Nature methods", "volume": "18", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "REMBI: Recommended Metadata for Biological Images-enabling reuse of microscopy data in biology.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The GDNF Family Ligands (GFLs) regulate neural development and kidney organogenesis by activating the RET receptor tyrosine kinase. Many RET-dependent developmental processes involve long-distance cell-cell communications or cell polarity, which includes cell migration and axon guidance. This suggests that spatiotemporally regulated subcellular localization of RET protein and appropriate propagation of RET signaling in cells are essential for the physiological function of the GFLs. Little is known, however, about the dynamics of RET protein in cells. Addressing this issue requires development of a system that allows visualization of RET in living cells. In this study, we report generation of a novel knock-in mouse line in which the RET-EGFP chimeric receptor is expressed under the Ret promoter. Unlike Ret-deficient mice that die after birth due to the absence of the enteric nervous system (ENS) and kidneys, Ret(RET-EGFP/RET-EGFP) mice were viable and grew to adulthood with no overt abnormality, which indicated that RET-EGFP exerts function comparable to RET. In neurons and ENS progenitors, RET-EGFP signals were detected both on the cell membrane and in the cytoplasm, the latter of which appeared as a punctate pattern. Time-lapse imaging of cultured neural cells and embryos revealed active transport of RET-EGFP puncta in neuronal axons and cell bodies. Immunohistochemical analyses detected RET-EGFP signals in early and recycling endosomes, indicating that RET-EGFP is trafficked via the endocytic pathway. Ret(RET-EGFP/RET-EGFP) mice enable visualization of functional RET protein in vivo for the first time and provide a unique platform to examine the dynamics and physiology of RET trafficking.", "classifications": [ { "id": "Enomoto", "label": "Group Enomoto", "parent": "Enomoto", "type": "group" }, { "id": "Enomoto", "label": "Team Enomoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Mukhamad", "last_name": "Sunardi", "name": null }, { "creator_type": "author", "first_name": "Keisuke", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Hideki", "last_name": "Enomoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/dgd.12740" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "34324195" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Movement", "descriptor_ui": "D002465", "major_topic": false }, { "descriptor": "Enteric Nervous System", "descriptor_ui": "D017615", "major_topic": true }, { "descriptor": "Glial Cell Line-Derived Neurotrophic Factor", "descriptor_ui": "D051100", "major_topic": true }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Aug", "date_precision": "unknown", "issue": "6", "normalized_date": null, "pages": "285-294", "proceedings_title": null, "publisher": "", "title": "Development, growth & differentiation", "volume": "63", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Live visualization of a functional RET-EGFP chimeric receptor in homozygous knock-in mice.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The ability to manipulate gene expression at a specific region in a tissue or cell culture system is critical for analysis of target gene function. For chick embryos/cells, several gene introduction/induction methods have been established such as those involving retrovirus, electroporation, sonoporation, and lipofection. However, these methods have limitations in the accurate induction of localized gene expression. Here we demonstrate the effective application of a recently developed light-dependent gene expression induction system (LightOn system) using the Neurospora crassa photoreceptor Vivid fused with a Gal4 DNA binding domain and p65 activation domain (GAVPO) that alters its activity in response to light stimulus in a primary chicken cell culture system. We show that the gene expression level and induction specificity in this system are strongly dependent on the light irradiation conditions. Especially, the irradiation interval is an important parameter for modulating gene expression; for shorter time intervals, higher induction specificity can be achieved. Further, by adjusting light irradiation conditions, the expression level in primary chicken cells can be regulated in a multiple step manner, in contrast to the binary expression seen for gene disruption or introduction (i.e., null or overexpression). This result indicates that the light-dependent expression control method can be a useful technique in chick models to examine how gene function is affected by gradual changes in gene expression levels. We applied this light induction system to regulate Sox9 expression in cultures of chick limb mesenchyme cells and showed that induced SOX9 protein could modulate expression of downstream genes.", "classifications": [ { "id": "Morishita", "label": "Group Morishita", "parent": "Morishita", "type": "group" }, { "id": "Morishita", "label": "Team Morishita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Keiichi", "last_name": "Kitajima", "name": null }, { "creator_type": "author", "first_name": "Naofumi", "last_name": "Kawahira", "name": null }, { "creator_type": "author", "first_name": "Sang-Woo", "last_name": "Lee", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Tamura", "name": null }, { "creator_type": "author", "first_name": "Yoshihiro", "last_name": "Morishita", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Ohtsuka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/dgd.12721" }, "pmcid": { "normalized": "PMC8252662" }, "pmid": { "normalized": "33733477" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Culture Techniques", "descriptor_ui": "D018929", "major_topic": true }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Chick Embryo", "descriptor_ui": "D002642", "major_topic": false }, { "descriptor": "Chickens", "descriptor_ui": "D002645", "major_topic": false }, { "descriptor": "Gene Expression Regulation, Developmental", "descriptor_ui": "D018507", "major_topic": false }, { "descriptor": "Light", "descriptor_ui": "D008027", "major_topic": true }, { "descriptor": "SOX9 Transcription Factor", "descriptor_ui": "D055758", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Apr", "date_precision": "unknown", "issue": "3", "normalized_date": null, "pages": "189-198", "proceedings_title": null, "publisher": "", "title": "Development, growth & differentiation", "volume": "63", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Light-induced local gene expression in primary chick cell culture system.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The female gametophytes of angiosperms contain cells with distinct functions, such as those that enable reproduction via pollen tube attraction and fertilization. Although the female gametophyte undergoes unique developmental processes, such as several rounds of nuclear division without cell plate formation and final cellularization, it remains unknown when and how the cell fate is determined during development. Here, we visualized the living dynamics of female gametophyte development and performed transcriptome analysis of individual cell types to assess the cell fate specifications in Arabidopsis thaliana. We recorded time lapses of the nuclear dynamics and cell plate formation from the 1-nucleate stage to the 7-cell stage after cellularization using an in vitro ovule culture system. The movies showed that the nuclear division occurred along the micropylar-chalazal (distal-proximal) axis. During cellularization, the polar nuclei migrated while associating with the forming edge of the cell plate, and then, migrated toward each other to fuse linearly. We also tracked the gene expression dynamics and identified that the expression of MYB98pro::GFP-MYB98, a synergid-specific marker, was initiated just after cellularization in the synergid, egg, and central cells and was then restricted to the synergid cells. This indicated that cell fates are determined immediately after cellularization. Transcriptome analysis of the female gametophyte cells of the wild-type and myb98 mutant revealed that the myb98 synergid cells had egg cell-like gene expression profiles. Although in myb98, egg cell-specific gene expression was properly initiated in the egg cells only after cellularization, but subsequently expressed ectopically in one of the 2 synergid cells. These results, together with the various initiation timings of the egg cell-specific genes, suggest complex regulation of the individual gametophyte cells, such as cellularization-triggered fate initiation, MYB98-dependent fate maintenance, cell morphogenesis, and organelle positioning. Our system of live-cell imaging and cell type-specific gene expression analysis provides insights into the dynamics and mechanisms of cell fate specifications in the development of female gametophytes in plants.", "classifications": [ { "id": "Ueda", "label": "Group Ueda", "parent": "Ueda", "type": "group" }, { "id": "Ueda", "label": "Team Ueda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Daichi", "last_name": "Susaki", "name": null }, { "creator_type": "author", "first_name": "Takamasa", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Maruyama", "name": null }, { "creator_type": "author", "first_name": "Minako", "last_name": "Ueda", "name": null }, { "creator_type": "author", "first_name": "Tetsuya", "last_name": "Higashiyama", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Kurihara", "name": null } ], "identifiers": { "doi": { "normalized": "10.1371/journal.pbio.3001123" }, "pmcid": { "normalized": "PMC7997040" }, "pmid": { "normalized": "33770073" } }, "mesh": [ { "descriptor": "Arabidopsis", "descriptor_ui": "D017360", "major_topic": false }, { "descriptor": "Arabidopsis Proteins", "descriptor_ui": "D029681", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Cell Nucleus", "descriptor_ui": "D002467", "major_topic": false }, { "descriptor": "Cytoplasm", "descriptor_ui": "D003593", "major_topic": false }, { "descriptor": "Gene Expression", "descriptor_ui": "D015870", "major_topic": false }, { "descriptor": "Gene Expression Profiling", "descriptor_ui": "D020869", "major_topic": false }, { "descriptor": "Gene Expression Regulation, Plant", "descriptor_ui": "D018506", "major_topic": false }, { "descriptor": "Magnoliopsida", "descriptor_ui": "D019684", "major_topic": false }, { "descriptor": "Morphogenesis", "descriptor_ui": "D009024", "major_topic": false }, { "descriptor": "Ovule", "descriptor_ui": "D056771", "major_topic": false }, { "descriptor": "Pollen Tube", "descriptor_ui": "D053205", "major_topic": false }, { "descriptor": "Promoter Regions, Genetic", "descriptor_ui": "D011401", "major_topic": false }, { "descriptor": "Transcription Factors", "descriptor_ui": "D014157", "major_topic": false }, { "descriptor": "Transcriptome", "descriptor_ui": "D059467", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Mar", "date_precision": "unknown", "issue": "3", "normalized_date": null, "pages": "e3001123", "proceedings_title": null, "publisher": "", "title": "PLoS biology", "volume": "19", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Dynamics of the cell fate specifications during female gametophyte development in Arabidopsis.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Navigation of fast migrating cells such as amoeba Dictyostelium and immune cells are tightly associated with their morphologies that range from steady polarized forms that support high directionality to those more complex and variable when making frequent turns. Model simulations are essential for quantitative understanding of these features and their origins, however systematic comparisons with real data are underdeveloped. Here, by employing deep-learning-based feature extraction combined with phase-field modeling framework, we show that a low dimensional feature space for 2D migrating cell morphologies obtained from the shape stereotype of keratocytes, Dictyostelium and neutrophils can be fully mapped by an interlinked signaling network of cell-polarization and protrusion dynamics. Our analysis links the data-driven shape analysis to the underlying causalities by identifying key parameters critical for migratory morphologies both normal and aberrant under genetic and pharmacological perturbations. The results underscore the importance of deciphering self-organizing states and their interplay when characterizing morphological phenotypes.", "classifications": [ { "id": "JPMJCR1923", "label": "JPMJCR1923", "researcher": "Satoshi Sawai", "type": "grant" }, { "id": "Sawai", "label": "Group Sawai", "parent": "Sawai", "type": "group" }, { "id": "Sawai", "label": "Team Sawai", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Daisuke", "last_name": "Imoto", "name": null }, { "creator_type": "author", "first_name": "Nen", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Akihiko", "last_name": "Nakajima", "name": null }, { "creator_type": "author", "first_name": "Gen", "last_name": "Honda", "name": null }, { "creator_type": "author", "first_name": "Motohiko", "last_name": "Ishida", "name": null }, { "creator_type": "author", "first_name": "Toyoko", "last_name": "Sugita", "name": null }, { "creator_type": "author", "first_name": "Sayaka", "last_name": "Ishihara", "name": null }, { "creator_type": "author", "first_name": "Koko", "last_name": "Katagiri", "name": null }, { "creator_type": "author", "first_name": "Chika", "last_name": "Okimura", "name": null }, { "creator_type": "author", "first_name": "Yoshiaki", "last_name": "Iwadate", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Sawai", "name": null } ], "identifiers": { "doi": { "normalized": "10.1371/journal.pcbi.1009237" }, "pmcid": { "normalized": "PMC8360578" }, "pmid": { "normalized": "34383753" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Movement", "descriptor_ui": "D002465", "major_topic": false }, { "descriptor": "Cell Polarity", "descriptor_ui": "D016764", "major_topic": false }, { "descriptor": "Cell Shape", "descriptor_ui": "D048430", "major_topic": false }, { "descriptor": "Cell Surface Extensions", "descriptor_ui": "D022081", "major_topic": false }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Cichlids", "descriptor_ui": "D023681", "major_topic": false }, { "descriptor": "Computational Biology", "descriptor_ui": "D019295", "major_topic": false }, { "descriptor": "Computer Simulation", "descriptor_ui": "D003198", "major_topic": false }, { "descriptor": "Deep Learning", "descriptor_ui": "D000077321", "major_topic": true }, { "descriptor": "Dictyostelium", "descriptor_ui": "D004023", "major_topic": false }, { "descriptor": "Fibroblasts", "descriptor_ui": "D005347", "major_topic": false }, { "descriptor": "HL-60 Cells", "descriptor_ui": "D018922", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Models, Biological", "descriptor_ui": "D008954", "major_topic": true } ], "publication": { "conference_name": null, "date": "2021 Aug", "date_precision": "unknown", "issue": "8", "normalized_date": null, "pages": "e1009237", "proceedings_title": null, "publisher": "", "title": "PLoS computational biology", "volume": "17", "year": 2021 }, "ssbd": { "database": [], "repository": [ "ssbd-repos-000167" ] }, "title": "Comparative mapping of crawling-cell morphodynamics in deep learning-based feature space.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Background: PD-L1 immunohistochemistry (IHC) is required to determine eligibility for pembrolizumab monotherapy in advanced non-small cell lung cancer (NSCLC) worldwide and for several other indications depending on the country. Four assays have been approved/CE-IVD marked, but PD-L1 IHC seems diversely implemented across regions and laboratories with the application of laboratory-developed tests (LDTs). Method: To assess practice of PD-L1 IHC and identify issues and disparities, the IASLC pathology committee conducted a global survey for pathologists from January to May 2019, comprising multiple questions on pre-analytical, analytical and post-analytical conditions. Result: 344 pathologists from 64 countries participated with 41% from Europe, 24% from North America, and 18% from Asia. Besides biopsies and resections, cellblocks were used by 75% of the participants and smears by 11%. The clone 22C3 was most commonly used (69%) followed by SP263 (51%). They were applied as a LDT by 40% and 30% of the users, respectively, and 76% of the participants developed at least one LDT. A half of the participants reported turnaround time (TAT) of ≤ 2 days, while 13% reported that of ≥ 5 days. Additionally, quality assurance (QA), formal training for scoring and standardized reporting were not implemented by 18%, 16% and 14% of the participants, respectively. Conclusion: Heterogeneity in PD-L1 testing is marked across regions and laboratories in terms of antibody clones, IHC assays, samples, TATs and QA measures. The lack of QA, formal training and standardized reporting stated by a significant minority identifies a need for additional QA measures and training opportunities.", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Mari", "last_name": "Mino-Kenudson", "name": null }, { "creator_type": "author", "first_name": "Nolwenn", "last_name": "Le Stang", "name": null }, { "creator_type": "author", "first_name": "Jillian B.", "last_name": "Daigneault", "name": null }, { "creator_type": "author", "first_name": "Andrew G.", "last_name": "Nicholson", "name": null }, { "creator_type": "author", "first_name": "Wendy A.", "last_name": "Cooper", "name": null }, { "creator_type": "author", "first_name": "Anja C.", "last_name": "Roden", "name": null }, { "creator_type": "author", "first_name": "Andre L.", "last_name": "Moreira", "name": null }, { "creator_type": "author", "first_name": "Erik", "last_name": "Thunnissen", "name": null }, { "creator_type": "author", "first_name": "Mauro", "last_name": "Papotti", "name": null }, { "creator_type": "author", "first_name": "Giuseppe", "last_name": "Pelosi", "name": null }, { "creator_type": "author", "first_name": "Noriko", "last_name": "Motoi", "name": null }, { "creator_type": "author", "first_name": "Claudia", "last_name": "Poleri", "name": null }, { "creator_type": "author", "first_name": "Elisabeth", "last_name": "Brambilla", "name": null }, { "creator_type": "author", "first_name": "Mary", "last_name": "Redman", "name": null }, { "creator_type": "author", "first_name": "Deepali", "last_name": "Jain", "name": null }, { "creator_type": "author", "first_name": "Sanja", "last_name": "Dacic", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null }, { "creator_type": "author", "first_name": "Ming", "last_name": "Sound Tsao", "name": null }, { "creator_type": "author", "first_name": "Fernando", "last_name": "Lopez-Rios", "name": null }, { "creator_type": "author", "first_name": "Johan", "last_name": "Botling", "name": null }, { "creator_type": "author", "first_name": "Gang", "last_name": "Chen", "name": null }, { "creator_type": "author", "first_name": "Teh-Ying", "last_name": "Chou", "name": null }, { "creator_type": "author", "first_name": "Fred R.", "last_name": "Hirsch", "name": null }, { "creator_type": "author", "first_name": "Mary", "last_name": "Beth Beasley", "name": null }, { "creator_type": "author", "first_name": "Alain", "last_name": "Borczuk", "name": null }, { "creator_type": "author", "first_name": "Lukas", "last_name": "Bubendorf", "name": null }, { "creator_type": "author", "first_name": "Jin-Haeng", "last_name": "Chung", "name": null }, { "creator_type": "author", "first_name": "David", "last_name": "Hwang", "name": null }, { "creator_type": "author", "first_name": "Dongmei", "last_name": "Lin", "name": null }, { "creator_type": "author", "first_name": "John", "last_name": "Longshore", "name": null }, { "creator_type": "author", "first_name": "Masayuki", "last_name": "Noguchi", "name": null }, { "creator_type": "author", "first_name": "Natasha", "last_name": "Rekhtman", "name": null }, { "creator_type": "author", "first_name": "Lynette", "last_name": "Sholl", "name": null }, { "creator_type": "author", "first_name": "William", "last_name": "Travis", "name": null }, { "creator_type": "author", "first_name": "Akihiko", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Murry W.", "last_name": "Wynes", "name": null }, { "creator_type": "author", "first_name": "Ignacio I.", "last_name": "Wistuba", "name": null }, { "creator_type": "author", "first_name": "Keith M.", "last_name": "Kerr", "name": null }, { "creator_type": "author", "first_name": "Sylvie", "last_name": "Lantuejoul", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.jtho.2020.12.026" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "33662578" } }, "mesh": [ { "descriptor": "Asia", "descriptor_ui": "D001208", "major_topic": false }, { "descriptor": "B7-H1 Antigen", "descriptor_ui": "D060890", "major_topic": false }, { "descriptor": "Biomarkers, Tumor", "descriptor_ui": "D014408", "major_topic": false }, { "descriptor": "Carcinoma, Non-Small-Cell Lung", "descriptor_ui": "D002289", "major_topic": true }, { "descriptor": "Europe", "descriptor_ui": "D005060", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Lung Neoplasms", "descriptor_ui": "D008175", "major_topic": true } ], "publication": { "conference_name": null, "date": "2021 Apr", "date_precision": "unknown", "issue": "4", "normalized_date": null, "pages": "686-696", "proceedings_title": null, "publisher": "", "title": "Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer", "volume": "16", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "IASLC Global Survey on PD-L1 Testing for Non-Small Cell Lung Cancer.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "INTRODUCTION: Because molecular-targeted drugs against MET exon 14 (METex14) skipping have been approved, molecular testing of the alteration has added to clinical guidelines. There are several such assays, but methodological issues have been reported. METHODS: METex14 skipping results from three assays (Oncomine DxTT, ArcherMET, and laboratory-developed reverse-transcriptase polymerase chain reaction test [LDT RT-PCR]) were compared in a relatively small series of the specimens diagnosed as advanced NSCLC (n = 50). RESULTS: The ArcherMET and LDT RT-PCR results were identical for all 50 samples, but eight samples had discordant results between Oncomine DxTT and the other two assays. All eight samples had METex14 skipping with Oncomine DxTT and wild-type signals with ArcherMET and LDT RT-PCR. The discordance might be caused by the homopolymeric error of the splice donor site with Oncomine DxTT, and false positives could be distinguished by relatively low read counts. CONCLUSIONS: Although the caution in detecting METex14 skipping focuses on false negatives in the literature, false positives were first noted at a relatively high frequency (8 of 26, 30.8%) in this study. According to the results of previous clinical trials using the other tyrosine kinase inhibitors, it could be surmised that MET inhibitor treatment in patients without METex14 skipping is detrimental. Clinicians need to be alert to the false positives that can lead to harmful treatments.", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Takashi", "last_name": "Teishikata", "name": null }, { "creator_type": "author", "first_name": "Kouya", "last_name": "Shiraishi", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Shinno", "name": null }, { "creator_type": "author", "first_name": "Yoshihisa", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Jumpei", "last_name": "Kashima", "name": null }, { "creator_type": "author", "first_name": "Takako", "last_name": "Ishiyama", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Taisuke", "last_name": "Mori", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.jtho.2021.07.028" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "34419686" } }, "mesh": [ { "descriptor": "Carcinoma, Non-Small-Cell Lung", "descriptor_ui": "D002289", "major_topic": true }, { "descriptor": "Exons", "descriptor_ui": "D005091", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Lung Neoplasms", "descriptor_ui": "D008175", "major_topic": true }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": false }, { "descriptor": "Proto-Oncogene Proteins c-met", "descriptor_ui": "D019859", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Dec", "date_precision": "unknown", "issue": "12", "normalized_date": null, "pages": "2133-2138", "proceedings_title": null, "publisher": "", "title": "Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer", "volume": "16", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "An Alert to Possible False Positives With a Commercial Assay for MET Exon 14 Skipping.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field.", "classifications": [ { "id": "Okamoto", "label": "Group Okamoto", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Daniel J.", "last_name": "Klionsky", "name": null }, { "creator_type": "author", "first_name": "Amal Kamal", "last_name": "Abdel-Aziz", "name": null }, { "creator_type": "author", "first_name": "Sara", "last_name": "Abdelfatah", "name": null }, { "creator_type": "author", "first_name": "Mahmoud", "last_name": "Abdellatif", "name": null }, { "creator_type": "author", "first_name": "Asghar", "last_name": "Abdoli", "name": null }, { "creator_type": "author", "first_name": "Steffen", "last_name": "Abel", "name": null }, { "creator_type": "author", "first_name": "Hagai", "last_name": "Abeliovich", "name": null }, { "creator_type": "author", "first_name": "Marie H.", "last_name": "Abildgaard", "name": null }, { "creator_type": "author", "first_name": "Yakubu Princely", "last_name": "Abudu", "name": null }, { "creator_type": "author", "first_name": "Abraham", "last_name": "Acevedo-Arozena", "name": null }, { "creator_type": "author", "first_name": "Iannis E.", "last_name": "Adamopoulos", "name": null }, { "creator_type": "author", "first_name": "Khosrow", "last_name": "Adeli", "name": null }, { "creator_type": "author", "first_name": "Timon E.", "last_name": "Adolph", "name": null }, { "creator_type": "author", "first_name": "Annagrazia", "last_name": "Adornetto", "name": null }, { "creator_type": "author", "first_name": "Elma", "last_name": "Aflaki", "name": null }, { "creator_type": "author", "first_name": "Galila", "last_name": "Agam", "name": null }, { "creator_type": "author", "first_name": "Anupam", "last_name": "Agarwal", "name": null }, { "creator_type": "author", "first_name": "Bharat B.", "last_name": "Aggarwal", "name": null }, { "creator_type": "author", "first_name": "Maria", "last_name": "Agnello", "name": null }, { "creator_type": "author", "first_name": "Patrizia", "last_name": "Agostinis", "name": null }, { "creator_type": "author", "first_name": "Javed N.", "last_name": "Agrewala", "name": null }, { "creator_type": "author", "first_name": "Alexander", "last_name": "Agrotis", "name": null }, { "creator_type": "author", "first_name": "Patricia V.", "last_name": "Aguilar", "name": null }, { "creator_type": "author", "first_name": "S. 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"last_name": "Zhang", "name": null }, { "creator_type": "author", "first_name": "Xiaolei", "last_name": "Zhang", "name": null }, { "creator_type": "author", "first_name": "Xiaoyan", "last_name": "Zhang", "name": null }, { "creator_type": "author", "first_name": "Xin", "last_name": "Zhang", "name": null }, { "creator_type": "author", "first_name": "Xinxin", "last_name": "Zhang", "name": null }, { "creator_type": "author", "first_name": "Xu Dong", "last_name": "Zhang", "name": null }, { "creator_type": "author", "first_name": "Yang", "last_name": "Zhang", "name": null }, { "creator_type": "author", "first_name": "Yanjin", "last_name": "Zhang", "name": null }, { "creator_type": "author", "first_name": "Yi", "last_name": "Zhang", "name": null }, { "creator_type": "author", "first_name": "Ying-Dong", "last_name": "Zhang", "name": null }, { "creator_type": "author", "first_name": "Yingmei", "last_name": "Zhang", "name": null }, { "creator_type": "author", "first_name": "Yuan-Yuan", "last_name": "Zhang", "name": null }, { "creator_type": "author", "first_name": "Yuchen", "last_name": "Zhang", "name": null }, { "creator_type": "author", "first_name": "Zhe", "last_name": "Zhang", "name": null }, { "creator_type": "author", "first_name": "Zhengguang", "last_name": "Zhang", "name": null }, { "creator_type": "author", "first_name": "Zhibing", "last_name": "Zhang", "name": null }, { "creator_type": "author", "first_name": "Zhihai", "last_name": "Zhang", "name": null }, { "creator_type": "author", "first_name": "Zhiyong", "last_name": "Zhang", "name": null }, { "creator_type": "author", "first_name": "Zili", "last_name": "Zhang", "name": null }, { "creator_type": "author", "first_name": "Haobin", "last_name": "Zhao", "name": null }, { "creator_type": "author", "first_name": "Lei", "last_name": "Zhao", "name": null }, { "creator_type": "author", "first_name": "Shuang", "last_name": "Zhao", "name": null }, { "creator_type": "author", "first_name": "Tongbiao", "last_name": "Zhao", "name": null }, { "creator_type": "author", "first_name": "Xiao-Fan", "last_name": "Zhao", "name": null }, { "creator_type": "author", "first_name": "Ying", "last_name": "Zhao", "name": null }, { "creator_type": "author", "first_name": "Yongchao", "last_name": "Zhao", "name": null }, { "creator_type": "author", "first_name": "Yongliang", "last_name": "Zhao", "name": null }, { "creator_type": "author", "first_name": "Yuting", "last_name": "Zhao", "name": null }, { "creator_type": "author", "first_name": "Guoping", "last_name": "Zheng", "name": null }, { "creator_type": "author", "first_name": "Kai", "last_name": "Zheng", "name": null }, { "creator_type": "author", "first_name": "Ling", "last_name": "Zheng", "name": null }, { "creator_type": "author", "first_name": "Shizhong", "last_name": "Zheng", "name": null }, { "creator_type": "author", "first_name": "Xi-Long", "last_name": "Zheng", "name": null }, { "creator_type": "author", "first_name": "Yi", "last_name": "Zheng", "name": null }, { "creator_type": "author", "first_name": "Zu-Guo", "last_name": "Zheng", "name": null }, { "creator_type": "author", "first_name": "Boris", "last_name": "Zhivotovsky", "name": null }, { "creator_type": "author", "first_name": "Qing", "last_name": "Zhong", "name": null }, { "creator_type": "author", "first_name": "Ao", "last_name": "Zhou", "name": null }, { "creator_type": "author", "first_name": "Ben", "last_name": "Zhou", "name": null }, { "creator_type": "author", "first_name": "Cefan", "last_name": "Zhou", "name": null }, { "creator_type": "author", "first_name": "Gang", "last_name": "Zhou", "name": null }, { "creator_type": "author", "first_name": "Hao", "last_name": "Zhou", "name": null }, { "creator_type": "author", "first_name": "Hong", "last_name": "Zhou", "name": null }, { "creator_type": "author", "first_name": "Hongbo", "last_name": "Zhou", "name": null }, { "creator_type": "author", "first_name": "Jie", "last_name": "Zhou", "name": null }, { "creator_type": "author", "first_name": "Jing", "last_name": "Zhou", "name": null }, { "creator_type": "author", "first_name": "Jing", "last_name": "Zhou", "name": null }, { "creator_type": "author", "first_name": "Jiyong", "last_name": "Zhou", "name": null }, { "creator_type": "author", "first_name": "Kailiang", "last_name": "Zhou", "name": null }, { "creator_type": "author", "first_name": "Rongjia", "last_name": "Zhou", "name": null }, { "creator_type": "author", "first_name": "Xu-Jie", "last_name": "Zhou", "name": null }, { "creator_type": "author", "first_name": "Yanshuang", "last_name": "Zhou", "name": null }, { "creator_type": "author", "first_name": "Yinghong", "last_name": "Zhou", "name": null }, { "creator_type": "author", "first_name": "Yubin", "last_name": "Zhou", "name": null }, { "creator_type": "author", "first_name": "Zheng-Yu", "last_name": "Zhou", "name": null }, { "creator_type": "author", "first_name": "Zhou", "last_name": "Zhou", "name": null }, { "creator_type": "author", "first_name": "Binglin", "last_name": "Zhu", "name": null }, { "creator_type": "author", "first_name": "Changlian", "last_name": "Zhu", "name": null }, { "creator_type": "author", "first_name": "Guo-Qing", "last_name": "Zhu", "name": null }, { "creator_type": "author", "first_name": "Haining", "last_name": "Zhu", "name": null }, { "creator_type": "author", "first_name": "Hongxin", "last_name": "Zhu", "name": null }, { "creator_type": "author", "first_name": "Hua", "last_name": "Zhu", "name": null }, { "creator_type": "author", "first_name": "Wei-Guo", "last_name": "Zhu", "name": null }, { "creator_type": "author", "first_name": "Yanping", "last_name": "Zhu", "name": null }, { "creator_type": "author", "first_name": "Yushan", "last_name": "Zhu", "name": null }, { "creator_type": "author", "first_name": "Haixia", "last_name": "Zhuang", "name": null }, { "creator_type": "author", "first_name": "Xiaohong", "last_name": "Zhuang", "name": null }, { "creator_type": "author", "first_name": "Katarzyna", "last_name": "Zientara-Rytter", "name": null }, { "creator_type": "author", "first_name": "Christine M.", "last_name": "Zimmermann", "name": null }, { "creator_type": "author", "first_name": "Elena", "last_name": "Ziviani", "name": null }, { "creator_type": "author", "first_name": "Teresa", "last_name": "Zoladek", "name": null }, { "creator_type": "author", "first_name": "Wei-Xing", "last_name": "Zong", "name": null }, { "creator_type": "author", "first_name": "Dmitry B.", "last_name": "Zorov", "name": null }, { "creator_type": "author", "first_name": "Antonio", "last_name": "Zorzano", "name": null }, { "creator_type": "author", "first_name": "Weiping", "last_name": "Zou", "name": null }, { "creator_type": "author", "first_name": "Zhen", "last_name": "Zou", "name": null }, { "creator_type": "author", "first_name": "Zhengzhi", "last_name": "Zou", "name": null }, { "creator_type": "author", "first_name": "Steven", "last_name": "Zuryn", "name": null }, { "creator_type": "author", "first_name": "Werner", "last_name": "Zwerschke", "name": null }, { "creator_type": "author", "first_name": "Beate", "last_name": "Brand-Saberi", "name": null }, { "creator_type": "author", "first_name": "X. Charlie", "last_name": "Dong", "name": null }, { "creator_type": "author", "first_name": "Chandra Shekar", "last_name": "Kenchappa", "name": null }, { "creator_type": "author", "first_name": "Zuguo", "last_name": "Li", "name": null }, { "creator_type": "author", "first_name": "Yong", "last_name": "Lin", "name": null }, { "creator_type": "author", "first_name": "Shigeru", "last_name": "Oshima", "name": null }, { "creator_type": "author", "first_name": "Yueguang", "last_name": "Rong", "name": null }, { "creator_type": "author", "first_name": "Judith C.", "last_name": "Sluimer", "name": null }, { "creator_type": "author", "first_name": "Christina L.", "last_name": "Stallings", "name": null }, { "creator_type": "author", "first_name": "Chun-Kit", "last_name": "Tong", "name": null } ], "identifiers": { "doi": { "normalized": "10.1080/15548627.2020.1797280" }, "pmcid": { "normalized": "PMC7996087" }, "pmid": { "normalized": "33634751" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Autophagosomes", "descriptor_ui": "D000071182", "major_topic": false }, { "descriptor": "Autophagy", "descriptor_ui": "D001343", "major_topic": true }, { "descriptor": "Autophagy-Related Proteins", "descriptor_ui": "D000071183", "major_topic": false }, { "descriptor": "Biological Assay", "descriptor_ui": "D001681", "major_topic": false }, { "descriptor": "Biomarkers", "descriptor_ui": "D015415", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Lysosomes", "descriptor_ui": "D008247", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Jan", "date_precision": "unknown", "issue": "1", "normalized_date": null, "pages": "1-382", "proceedings_title": null, "publisher": "", "title": "Autophagy", "volume": "17", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)(1).", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Contraction of vascular smooth muscle is regulated primarily by calcium concentration and secondarily by ROCK activity within the cells. In contrast to the wealth of information regarding regulation of calcium concentration, little is known about the spatiotemporal regulation of ROCK activity in live blood vessels. Here, we report ROCK activation in subcutaneous arterioles in a transgenic mouse line that expresses a genetically encoded ROCK biosensor based on the principle of Frster resonance energy transfer by two-photon excitation in vivo imaging. Rapid vasospasm was induced upon laser ablation of arterioles, concomitant with a transient increase in calcium concentration in arteriolar smooth muscles. Unlike the increase in calcium concentration, vasoconstriction and ROCK activation continued for several minutes after irradiation. Both the ROCK inhibitor, fasudil, and the ganglionic nicotinic acetylcholine receptor blocker, hexamethonium, inhibited laser-induced ROCK activation and reduced the duration of vasospasm at the segments distant from the irradiated point. These observations suggest that vasoconstriction is initially triggered by a rapid surge of cytoplasmic calcium and then maintained by sympathetic nerve-mediated ROCK activation.", "classifications": [], "creators": [ { "creator_type": "author", "first_name": "Ayako", "last_name": "Imanishi", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Ichise", "name": null }, { "creator_type": "author", "first_name": "Chuyun", "last_name": "Fan", "name": null }, { "creator_type": "author", "first_name": "Yasuaki", "last_name": "Nakagawa", "name": null }, { "creator_type": "author", "first_name": "Koichiro", "last_name": "Kuwahara", "name": null }, { "creator_type": "author", "first_name": "Kenta", "last_name": "Sumiyama", "name": null }, { "creator_type": "author", "first_name": "Michiyuki", "last_name": "Matsuda", "name": null }, { "creator_type": "author", "first_name": "Kenta", "last_name": "Terai", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.ajpath.2020.09.012" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "33069718" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Autonomic Nervous System", "descriptor_ui": "D001341", "major_topic": false }, { "descriptor": "Calcium Signaling", "descriptor_ui": "D020013", "major_topic": false }, { "descriptor": "Fluorescence Resonance Energy Transfer", "descriptor_ui": "D031541", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Transgenic", "descriptor_ui": "D008822", "major_topic": false }, { "descriptor": "Muscle, Smooth, Vascular", "descriptor_ui": "D009131", "major_topic": false }, { "descriptor": "rho-Associated Kinases", "descriptor_ui": "D054460", "major_topic": false }, { "descriptor": "Vasoconstriction", "descriptor_ui": "D014661", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Jan", "date_precision": "unknown", "issue": "1", "normalized_date": null, "pages": "194-203", "proceedings_title": null, "publisher": "", "title": "The American journal of pathology", "volume": "191", "year": 2021 }, "ssbd": { "database": [ "ssbd-database-000220" ], "repository": [ "ssbd-repos-000220" ] }, "title": "Visualization of Spatially-Controlled Vasospasm by Sympathetic Nerve-Mediated ROCK Activation.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND/AIM: We established a data-driven method for extracting spatial patterns of dose distribution associated with radiation injuries, based on patients with prostate cancer who underwent iodine-125 (I-125) seed implantation. PATIENTS AND METHODS: Seventy-five patients underwent I-125 seed implantation for prostate cancer. We modeled the severity of lower urinary tract symptoms (LUTS) to be estimated using a linear model, which is formulated as an inner product between the dose distribution D and voxel-wise radiosensitivity B inside the prostate. For the estimation, tensor regression based on a low-rank decomposition with generalized fused lasso penalty was applied. RESULTS: The spatial distribution of B was visually assessed. Positive parameters appeared dominantly in the region close to the urethra and the prostate base. CONCLUSION: Our tensor regression-based model can predict intra-organ radiosensitivity in a data-driven manner, providing a compelling parameter distribution associated with the development of LUTS after I-125 seed implantation for prostate cancer.", "classifications": [ { "id": "Hamamoto", "label": "Group Hamamoto", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Kazuma", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Naoya", "last_name": "Murakami", "name": null }, { "creator_type": "author", "first_name": "Kana", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Inaba", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Igaki", "name": null }, { "creator_type": "author", "first_name": "Ryuji", "last_name": "Hamamoto", "name": null }, { "creator_type": "author", "first_name": "Jun", "last_name": "Itami", "name": null } ], "identifiers": { "doi": { "normalized": "10.21873/invivo.12283" }, "pmcid": { "normalized": "PMC7880750" }, "pmid": { "normalized": "33402501" } }, "mesh": [ { "descriptor": "Brachytherapy", "descriptor_ui": "D001918", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Iodine Radioisotopes", "descriptor_ui": "D007457", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Prostatic Neoplasms", "descriptor_ui": "D011471", "major_topic": true }, { "descriptor": "Radiation Tolerance", "descriptor_ui": "D011836", "major_topic": false }, { "descriptor": "Radiotherapy Dosage", "descriptor_ui": "D011879", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Jan-Feb", "date_precision": "unknown", "issue": "1", "normalized_date": null, "pages": "489-497", "proceedings_title": null, "publisher": "", "title": "In vivo (Athens, Greece)", "volume": "35", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Tensor Regression-based Model to Investigate Heterogeneous Spatial Radiosensitivity After I-125 Seed Implantation for Prostate Cancer.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Chromosome segregation errors in oocytes lead to the production of aneuploid eggs, which are the leading cause of pregnancy loss and of several congenital diseases such as Down syndrome. The frequency of chromosome segregation errors in oocytes increases with maternal age, especially at a late stage of reproductive life. How aging at various life stages affects oocytes differently remains poorly understood. In this study, we describe aging-associated changes in the transcriptome profile of mouse oocytes throughout reproductive life. Our single-oocyte comprehensive RNA sequencing using RamDA-seq revealed that oocytes undergo transcriptome changes at a late reproductive stage, whereas their surrounding cumulus cells exhibit transcriptome changes at an earlier stage. Calorie restriction, a paradigm that reportedly prevents aging-associated egg aneuploidy, promotes a transcriptome shift in oocytes with the up-regulation of genes involved in chromosome segregation. This shift is accompanied by the improved maintenance of chromosomal cohesin, the loss of which is a hallmark of oocyte aging and causes chromosome segregation errors. These findings have implications for understanding how oocytes undergo aging-associated functional decline throughout their reproductive life in a context-dependent manner.", "classifications": [ { "id": "JPMJCR1926", "label": "JPMJCR1926", "researcher": "Hironobu Fujiwara", "type": "grant" }, { "id": "Fujiwara", "label": "Group Fujiwara", "parent": "Fujiwara", "type": "group" }, { "id": "Nikaido", "label": "Group Nikaido", "parent": "Fujiwara", "type": "group" }, { "id": "Fujiwara", "label": "Team Fujiwara", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Tappei", "last_name": "Mishina", "name": null }, { "creator_type": "author", "first_name": "Namine", "last_name": "Tabata", "name": null }, { "creator_type": "author", "first_name": "Tetsutaro", "last_name": "Hayashi", "name": null }, { "creator_type": "author", "first_name": "Mika", "last_name": "Yoshimura", "name": null }, { "creator_type": "author", "first_name": "Mana", "last_name": "Umeda", "name": null }, { "creator_type": "author", "first_name": "Masashi", "last_name": "Mori", "name": null }, { "creator_type": "author", "first_name": "Yayoi", "last_name": "Ikawa", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Hamada", "name": null }, { "creator_type": "author", "first_name": "Itoshi", "last_name": "Nikaido", "name": null }, { "creator_type": "author", "first_name": "Tomoya S.", "last_name": "Kitajima", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/acel.13428" }, "pmcid": { "normalized": "PMC8373347" }, "pmid": { "normalized": "34245092" } }, "mesh": [ { "descriptor": "Aging", "descriptor_ui": "D000375", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Caloric Restriction", "descriptor_ui": "D031204", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Gene Expression Profiling", "descriptor_ui": "D020869", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Oocytes", "descriptor_ui": "D009865", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Aug", "date_precision": "unknown", "issue": "8", "normalized_date": null, "pages": "e13428", "proceedings_title": null, "publisher": "", "title": "Aging cell", "volume": "20", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Single-oocyte transcriptome analysis reveals aging-associated effects influenced by life stage and calorie restriction.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: We showed previously that a thick three-dimensional epidermal equivalent can be constructed with passaged keratinocytes on a patterned surface. MATERIAL AND METHODS: We first carried out computer simulations of a three-dimensional epidermal equivalent model built on close-packed arrays of 10 microm, 15 microm, 20 microm, 30 microm, and 60 microm diameter pillars. Based on these predictions, we evaluated epidermal equivalents built on a series of porous plastic membranes bearing arrays of pillars 15 microm, 20 microm, 25 microm, 30 microm, and 50 microm in diameter. RESULTS: The simulations predicted that a model having near-physiological thickness would be formed on 15 ~ 30 microm pillars. In the results of in vitro study, the thickest epidermal equivalent was obtained on the 20 microm pillars. Epidermal differentiation markers, filaggrin and loricrin, were expressed at the upper layer of the epidermal equivalent model, and tight-junction proteins, claudin-1 and ZO-1, were expressed on the cell membranes. BrdU-positive cells were observed at the base and also at the top of the pillars. CONCLUSION: The results of the study suggested that mathematical modeling might be a useful tool to guide biological studies.", "classifications": [ { "id": "Nagayama", "label": "Group Nagayama", "parent": "Fujiwara", "type": "group" }, { "id": "Fujiwara", "label": "Team Fujiwara", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Junichi", "last_name": "Kumamoto", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Fujimoto", "name": null }, { "creator_type": "author", "first_name": "Yasuaki", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Kota", "last_name": "Ohno", "name": null }, { "creator_type": "author", "first_name": "Masaharu", "last_name": "Nagayama", "name": null }, { "creator_type": "author", "first_name": "Mitsuhiro", "last_name": "Denda", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/srt.13035" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "33760308" } }, "mesh": [ { "descriptor": "Epidermis", "descriptor_ui": "D004817", "major_topic": true }, { "descriptor": "Keratinocytes", "descriptor_ui": "D015603", "major_topic": true } ], "publication": { "conference_name": null, "date": "2021 Sep", "date_precision": "unknown", "issue": "5", "normalized_date": null, "pages": "863-870", "proceedings_title": null, "publisher": "", "title": "Skin research and technology : official journal of International Society for Bioengineering and the Skin (ISBS) [and] International Society for Digital Imaging of Skin (ISDIS) [and] International Society for Skin Imaging (ISSI)", "volume": "27", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Substrate membrane bearing close-packed array of micron-level pillars incrassates air-exposed three-dimensional epidermal equivalent model.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Stem cell (SC) proliferation and differentiation organize tissue homeostasis. However, how SCs regulate coordinate tissue scaling in dynamic organs remain unknown. Here, we delineate SC regulations in dynamic skin. We found that interfollicular epidermal SCs (IFESCs) shape basal epidermal proliferating clusters (EPCs) in expanding abdominal epidermis of pregnant mice and proliferating plantar epidermis. EPCs consist of IFESC-derived Tbx3(+)-basal cells (Tbx3(+)-BCs) and their neighboring cells where Adam8-extracellular signal-regulated kinase signaling is activated. Clonal lineage tracing revealed that Tbx3(+)-BC clones emerge in the abdominal epidermis during pregnancy, followed by differentiation after parturition. In the plantar epidermis, Tbx3(+)-BCs are sustained as long-lived SCs to maintain EPCs invariably. We showed that Tbx3(+)-BCs are vasculature-dependent IFESCs and identified mechanical stretch as an external cue for the vasculature-driven EPC formation. Our results uncover vasculature-mediated IFESC regulations, which explain how the epidermis adjusts its size in orchestration with dermal constituents in dynamic skin.", "classifications": [ { "id": "Fujiwara", "label": "Group Fujiwara", "parent": "Fujiwara", "type": "group" }, { "id": "Toyoshima", "label": "Group Toyoshima", "parent": "Toyoshima", "type": "group" }, { "id": "Yamamoto", "label": "Group Yamamoto", "parent": "Toyoshima", "type": "group" }, { "id": "Fujiwara", "label": "Team Fujiwara", "type": "team" }, { "id": "Toyoshima", "label": "Team Toyoshima", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Ryo", "last_name": "Ichijo", "name": null }, { "creator_type": "author", "first_name": "Mio", "last_name": "Kabata", "name": null }, { "creator_type": "author", "first_name": "Hiroyasu", "last_name": "Kidoya", "name": null }, { "creator_type": "author", "first_name": "Fumitaka", "last_name": "Muramatsu", "name": null }, { "creator_type": "author", "first_name": "Riki", "last_name": "Ishibashi", "name": null }, { "creator_type": "author", "first_name": "Kota", "last_name": "Abe", "name": null }, { "creator_type": "author", "first_name": "Ko", "last_name": "Tsutsui", "name": null }, { "creator_type": "author", "first_name": "Hirokazu", "last_name": "Kubo", "name": null }, { "creator_type": "author", "first_name": "Yui", "last_name": "Iizuka", "name": null }, { "creator_type": "author", "first_name": "Satsuki", "last_name": "Kitano", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Miyachi", "name": null }, { "creator_type": "author", "first_name": "Yoshiaki", "last_name": "Kubota", "name": null }, { "creator_type": "author", "first_name": "Hironobu", "last_name": "Fujiwara", "name": null }, { "creator_type": "author", "first_name": "Aiko", "last_name": "Sada", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Fumiko", "last_name": "Toyoshima", "name": null } ], "identifiers": { "doi": { "normalized": "10.1126/sciadv.abd2575" }, "pmcid": { "normalized": "PMC7875541" }, "pmid": { "normalized": "33568475" } }, "mesh": [], "publication": { "conference_name": null, "date": "2021 Feb", "date_precision": "unknown", "issue": "7", "normalized_date": null, "pages": "eabd2575", "proceedings_title": null, "publisher": "", "title": "Science advances", "volume": "7", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Vasculature-driven stem cell population coordinates tissue scaling in dynamic organs.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "ALK, ROS1 and NTRK fusions are involved in the tumorigenesis of various organs, including colorectal cancer. This study aims to clarify the prevalence of these fusions in colorectal cancer in the Japanese population. Immunohistochemical analysis of 1012 specimens of colorectal cancer revealed two NTRK-positive cases (0.2%) whereas no ALK- or ROS1-positive cases were identified. Reverse transcription polymerase chain reaction (RT-PCR) detected an LMNA-NTRK1 fusion in a case of adenosquamous carcinoma and a TPM3-NTRK1 fusion in a case of tubular adenocarcinoma. Both NTRK1 fusion-positive cases lacked activating mutations in KRAS and BRAF and were mismatch repair-deficient with loss of MLH1 and PMS2 expression and MLH1 promoter methylation. Our results show that receptor tyrosine kinase fusions are rare but present in colorectal cancers in Japanese patients, with a prevalence similar to that reported in other countries.", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Junpei", "last_name": "Yonemaru", "name": null }, { "creator_type": "author", "first_name": "Taiki", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Takayanagi", "name": null }, { "creator_type": "author", "first_name": "Tomoaki", "last_name": "Naka", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null }, { "creator_type": "author", "first_name": "Yukihide", "last_name": "Kanemitsu", "name": null }, { "creator_type": "author", "first_name": "Kouya", "last_name": "Shiraishi", "name": null }, { "creator_type": "author", "first_name": "Shigeki", "last_name": "Sekine", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/pin.13082" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "33631044" } }, "mesh": [ { "descriptor": "Adenocarcinoma", "descriptor_ui": "D000230", "major_topic": false }, { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Biomarkers, Tumor", "descriptor_ui": "D014408", "major_topic": false }, { "descriptor": "Carcinoma, Adenosquamous", "descriptor_ui": "D018196", "major_topic": false }, { "descriptor": "Colonic Neoplasms", "descriptor_ui": "D003110", "major_topic": false }, { "descriptor": "Colorectal Neoplasms", "descriptor_ui": "D015179", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Immunohistochemistry", "descriptor_ui": "D007150", "major_topic": false }, { "descriptor": "Japan", "descriptor_ui": "D007564", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Oncogene Proteins, Fusion", "descriptor_ui": "D015514", "major_topic": true }, { "descriptor": "Protein-Tyrosine Kinases", "descriptor_ui": "D011505", "major_topic": false }, { "descriptor": "Proto-Oncogene Proteins", "descriptor_ui": "D011518", "major_topic": false }, { "descriptor": "Receptor, trkA", "descriptor_ui": "D020917", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 May", "date_precision": "unknown", "issue": "5", "normalized_date": null, "pages": "355-359", "proceedings_title": null, "publisher": "", "title": "Pathology international", "volume": "71", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "NTRK fusion-positive colorectal cancer in Japanese population.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Acoustic cavitation occurs in ultrasonic treatment causing various phenomena such as chemical synthesis, chemical decomposition, and emulsification. Nonlinear oscillations of cavitation bubbles are assumed to be responsible for these phenomena, and the neighboring bubbles may interact each other. In the present study, we numerically investigated the dynamic behavior of cavitation bubbles in multi-bubble systems. The results reveal that the oscillation amplitude of a cavitation bubble surrounded by other bubbles in a multi-bubble system becomes larger compared with that in the single-bubble case. It is found that this is caused by an acoustic wake effect, which reduces the pressure near a bubble surrounded by other bubbles and increases the time delay between the bubble contraction/expansion cycles and sound pressure oscillations. A new parameter, called \"cover ratio\" is introduced to quantitatively evaluate the variation in the bubble oscillation amplitude, the time delay, and the maximum bubble radius.", "classifications": [ { "id": "Yamamoto", "label": "Group Yamamoto", "parent": "Toyoshima", "type": "group" }, { "id": "Toyoshima", "label": "Team Toyoshima", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Takuya", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Sergey V.", "last_name": "Komarov", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.ultsonch.2021.105734" }, "pmcid": { "normalized": "PMC8408526" }, "pmid": { "normalized": "34469851" } }, "mesh": [], "publication": { "conference_name": null, "date": "2021 Oct", "date_precision": "unknown", "issue": "", "normalized_date": null, "pages": "105734", "proceedings_title": null, "publisher": "", "title": "Ultrasonics sonochemistry", "volume": "78", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Enhancement of oscillation amplitude of cavitation bubble due to acoustic wake effect in multibubble environment.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The recent report by Fan et al alleged that the ProPerDP method is inadequate for the detection of protein persulfidation. Upon careful evaluation of their work, we conclude that the claim made by Fan et al is not supported by their data, rather founded in methodological shortcomings. It is understood that the ProPerDP method generates a mixture of cysteine-containing and non-cysteine-containing peptides. Instead, Fan et al suggested that the detection of non-cysteine-containing peptides indicates nonspecific alkylation at noncysteine residues. However, if true, then such peptides would not be released by reduction and therefore not appear as products in the reported workflow. Moreover, the authors' biological assessment of ProPerDP using Escherichia coli mutants was based on assumptions that have not been confirmed by other methods. We conclude that Fan et al did not rigorously assess the method and that ProPerDP remains a reliable approach for analyses of protein per/polysulfidation.", "classifications": [ { "id": "Akaike", "label": "Group Akaike", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Eva", "last_name": "Doka", "name": null }, { "creator_type": "author", "first_name": "Elias S. J.", "last_name": "Arner", "name": null }, { "creator_type": "author", "first_name": "Edward E.", "last_name": "Schmidt", "name": null }, { "creator_type": "author", "first_name": "Tobias P.", "last_name": "Dick", "name": null }, { "creator_type": "author", "first_name": "Albert", "last_name": "van der Vliet", "name": null }, { "creator_type": "author", "first_name": "Jing", "last_name": "Yang", "name": null }, { "creator_type": "author", "first_name": "Reka", "last_name": "Szatmari", "name": null }, { "creator_type": "author", "first_name": "Tamas", "last_name": "Ditroi", "name": null }, { "creator_type": "author", "first_name": "John L.", "last_name": "Wallace", "name": null }, { "creator_type": "author", "first_name": "Giuseppe", "last_name": "Cirino", "name": null }, { "creator_type": "author", "first_name": "Kenneth", "last_name": "Olson", "name": null }, { "creator_type": "author", "first_name": "Hozumi", "last_name": "Motohashi", "name": null }, { "creator_type": "author", "first_name": "Jon M.", "last_name": "Fukuto", "name": null }, { "creator_type": "author", "first_name": "Michael D.", "last_name": "Pluth", "name": null }, { "creator_type": "author", "first_name": "Martin", "last_name": "Feelisch", "name": null }, { "creator_type": "author", "first_name": "Takaaki", "last_name": "Akaike", "name": null }, { "creator_type": "author", "first_name": "David A.", "last_name": "Wink", "name": null }, { "creator_type": "author", "first_name": "Louis J.", "last_name": "Ignarro", "name": null }, { "creator_type": "author", "first_name": "Peter", "last_name": "Nagy", "name": null } ], "identifiers": { "doi": { "normalized": "10.1126/sciadv.abe7006" }, "pmcid": { "normalized": "PMC8059920" }, "pmid": { "normalized": "33883133" } }, "mesh": [], "publication": { "conference_name": null, "date": "2021 Apr", "date_precision": "unknown", "issue": "17", "normalized_date": null, "pages": "eabe7006", "proceedings_title": null, "publisher": "", "title": "Science advances", "volume": "7", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Comment on \"Evidence that the ProPerDP method is inadequate for protein persulfidation detection due to lack of specificity\".", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "ANGUSTIFOLIA (AN) is a plant-specific subfamily of the CtBP/BARS/AN family, characterized by a plant-specific C-terminal domain of approximately 200 amino acids. Previously, we revealed that double knockout (DKO) lines of Physcomitrium (Physcomitrella) patens ANGUSTIFOLIA genes (PpAN1-1 and PpAN1-2) show defects in gametophore height and the lengths of the seta and foot region of sporophytes, by reduced cell elongation. In addition to two canonical ANs, the genome of P. patens has two atypical ANs without a coding region for a plant-specific C-terminus (PpAN2-1 and PpAN2-2); these were investigated in this study. Similar to PpAN1s, both promoters of the PpAN2 genes were highly active in the stems of haploid gametophores and in the middle-to-basal region of young diploid sporophytes that develop into the seta and foot. Analyses of PpAN2-1/2-2 DKO and PpAN quadruple knockout (QKO) lines implied that these four AN genes have partially redundant functions to regulate cell elongation in their expression regions. Transgenic strains harboring P. patens alpha-tubulin fused to green fluorescent protein, which were generated from a QKO line, showed that the orientation of the microtubules in the gametophore tips in the PpAN QKO lines was unchanged from the wild-type and PpAN1-1/1-2 DKO plants. In addition to both PpAN2-1 and PpAN2-2, short Arabidopsis AN without the C-terminus of 200 amino acids could rescue the Arabidopsis thaliana an-1 phenotypes, implying AN activity is dependent on the N-terminal regions.", "classifications": [ { "id": "Sato", "label": "Group Sato", "parent": "Tsuchiya", "type": "group" }, { "id": "Tsuchiya", "label": "Team Tsuchiya", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Katsuaki", "last_name": "Takechi", "name": null }, { "creator_type": "author", "first_name": "Hiroaki", "last_name": "Nagase", "name": null }, { "creator_type": "author", "first_name": "Tomoyuki", "last_name": "Furuya", "name": null }, { "creator_type": "author", "first_name": "Koro", "last_name": "Hattori", "name": null }, { "creator_type": "author", "first_name": "Yoshikatsu", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Kensuke", "last_name": "Miyajima", "name": null }, { "creator_type": "author", "first_name": "Tomofumi", "last_name": "Higuchi", "name": null }, { "creator_type": "author", "first_name": "Ryuya", "last_name": "Matsuda", "name": null }, { "creator_type": "author", "first_name": "Susumu", "last_name": "Takio", "name": null }, { "creator_type": "author", "first_name": "Hirokazu", "last_name": "Tsukaya", "name": null }, { "creator_type": "author", "first_name": "Hiroyoshi", "last_name": "Takano", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/tpj.15121" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "33280196" } }, "mesh": [ { "descriptor": "Arabidopsis", "descriptor_ui": "D017360", "major_topic": false }, { "descriptor": "Arabidopsis Proteins", "descriptor_ui": "D029681", "major_topic": false }, { "descriptor": "Bryopsida", "descriptor_ui": "D019068", "major_topic": false }, { "descriptor": "Gene Expression Regulation, Plant", "descriptor_ui": "D018506", "major_topic": false }, { "descriptor": "Microtubules", "descriptor_ui": "D008870", "major_topic": false }, { "descriptor": "Repressor Proteins", "descriptor_ui": "D012097", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Mar", "date_precision": "unknown", "issue": "5", "normalized_date": null, "pages": "1390-1399", "proceedings_title": null, "publisher": "", "title": "The Plant journal : for cell and molecular biology", "volume": "105", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Two atypical ANGUSTIFOLIA without a plant-specific C-terminus regulate gametophore and sporophyte shapes in the moss Physcomitrium (Physcomitrella) patens.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The dynamics of biochemical reaction networks are considered to be responsible for biological functions in living systems. Since real networks are immense and complicated, it is difficult to determine which reactions can cause a significant change of dynamical behaviors, namely, bifurcations. Also to what extent numerical results of network systems depend on the chosen kinetic rate parameters is not known. In this paper, an analytical setting that splits the information of the dynamics into the network structure and reaction kinetics is introduced. This setting possesses a factorization structure for some class of network systems which allows one to determine which subnetworks are responsible for the occurrence of a bifurcation. Subsequently, the bifurcation criteria are reformulated in a manner that allows the efficient determination of relevant reactions for bifurcations.", "classifications": [ { "id": "Mochizuki", "label": "Group Mochizuki", "parent": "Eiraku", "type": "group" }, { "id": "Eiraku", "label": "Team Eiraku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Takashi", "last_name": "Okada", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Mochizuki", "name": null }, { "creator_type": "author", "first_name": "Mikio", "last_name": "Furuta", "name": null }, { "creator_type": "author", "first_name": "Je-Chiang", "last_name": "Tsai", "name": null } ], "identifiers": { "doi": { "normalized": "10.1103/physreve.103.062212" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "34271769" } }, "mesh": [], "publication": { "conference_name": null, "date": "2021 Jun", "date_precision": "unknown", "issue": "6-1", "normalized_date": null, "pages": "062212", "proceedings_title": null, "publisher": "", "title": "Physical review. E", "volume": "103", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Flux-augmented bifurcation analysis in chemical reaction network systems.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The eighth edition of the Lung Cancer Handling Regulations defines the pathological findings of “invasion” in the pathological diagnosis of lung adenocarcinoma and terms it as adenocarcinoma in situ/minimally invasive carcinoma. In addition, the invasion diameter (tumor diameter excluding the lepidic growth region) was adopted as the pT factor, and the classification further reflected prognosis (degree of invasion/progression). Meanwhile, computed tomography imaging-based classification, where the consolidation (nodule) diameter excluding the ground glass shadow area was defined as cT, and the classification reflected the pathological invasion diameter. It is clear that the revision of the eighth edition has reduced discrepancies in the pathological findings of lung adenocarcinoma in CT imaging and assessment of the degree of invasion and progression. At the same time, the 8th edition is not yet accurate enough. Therefore, we will discuss imaging techniques to better predict the extent of adenocarcinoma invasion and progression, based on our own findings and the literature.", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yukinori", "last_name": "Sakao", "name": null }, { "creator_type": "author", "first_name": "Hiroaki", "last_name": "Kuroda", "name": null }, { "creator_type": "author", "first_name": "Yuichi", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Yoshikane", "last_name": "Yamauchi", "name": null }, { "creator_type": "author", "first_name": "Fumi", "last_name": "Yokote", "name": null }, { "creator_type": "author", "first_name": "Masufumi", "last_name": "Kawamura", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null } ], "identifiers": { "doi": { "normalized": "10.21037/jtd-20-844" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "33569217" } }, "mesh": [], "publication": { "conference_name": null, "date": "2021 Jan", "date_precision": "unknown", "issue": "1", "normalized_date": null, "pages": "366-371", "proceedings_title": null, "publisher": "", "title": "Journal of Thoracic Disease", "volume": "13", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Radiological imaging and pathological findings of small lung adenocarcinoma: a narrative review.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The mechanism of intercellular transport of Wnt ligands is still a matter of debate. To better understand this issue, we examined the distribution and dynamics of Wnt8 in Xenopus embryos. While Venus-tagged Wnt8 was found on the surfaces of cells close to Wnt-producing cells, we also detected its dispersal over distances of 15 cell diameters. A combination of fluorescence correlation spectroscopy and quantitative imaging suggested that only a small proportion of Wnt8 ligands diffuses freely, whereas most Wnt8 molecules are bound to cell surfaces. Fluorescence decay after photoconversion showed that Wnt8 ligands bound on cell surfaces decrease exponentially, suggesting a dynamic exchange of bound forms of Wnt ligands. Mathematical modeling based on this exchange recapitulates a graded distribution of bound, but not free, Wnt ligands. Based on these results, we propose that Wnt distribution in tissues is controlled by a dynamic exchange of its abundant bound and rare free populations.", "classifications": [ { "id": "JPMJCR1922", "label": "JPMJCR1922", "researcher": "Mototsugu Eiraku", "type": "grant" } ], "creators": [ { "creator_type": "author", "first_name": "Yusuke", "last_name": "Mii", "name": null }, { "creator_type": "author", "first_name": "Kenichi", "last_name": "Nakazato", "name": null }, { "creator_type": "author", "first_name": "Chan-Gi", "last_name": "Pack", "name": null }, { "creator_type": "author", "first_name": "Takafumi", "last_name": "Ikeda", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Sako", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Mochizuki", "name": null }, { "creator_type": "author", "first_name": "Masanori", "last_name": "Taira", "name": null }, { "creator_type": "author", "first_name": "Shinji", "last_name": "Takada", "name": null } ], "identifiers": { "doi": { "normalized": "10.7554/elife.55108" }, "pmcid": { "normalized": "PMC8139832" }, "pmid": { "normalized": "33904408" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Diffusion", "descriptor_ui": "D004058", "major_topic": false }, { "descriptor": "Embryo, Nonmammalian", "descriptor_ui": "D004625", "major_topic": false }, { "descriptor": "Extracellular Space", "descriptor_ui": "D005110", "major_topic": false }, { "descriptor": "Frizzled-Related Proteins", "descriptor_ui": "D000099274", "major_topic": false }, { "descriptor": "Intracellular Signaling Peptides and Proteins", "descriptor_ui": "D047908", "major_topic": false }, { "descriptor": "Ligands", "descriptor_ui": "D008024", "major_topic": false }, { "descriptor": "Membrane Proteins", "descriptor_ui": "D008565", "major_topic": false }, { "descriptor": "Spectrometry, Fluorescence", "descriptor_ui": "D013050", "major_topic": false }, { "descriptor": "Wnt Proteins", "descriptor_ui": "D051153", "major_topic": false }, { "descriptor": "Xenopus laevis", "descriptor_ui": "D014982", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021/4/27", "date_precision": "unknown", "issue": "", "normalized_date": null, "pages": "e55108", "proceedings_title": null, "publisher": "", "title": "eLife", "volume": "10", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Quantitative analyses reveal extracellular dynamics of Wnt ligands in Xenopus embryos", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8139832/", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Chemosensitivity to cisplatin derivatives varies among individual patients with intractable malignancies including ovarian cancer, while how to unlock the resistance remain unknown. Ovarian cancer tissues were collected the debulking surgery in discovery- (n = 135) and validation- (n = 47) cohorts, to be analyzed with high-throughput automated immunohistochemistry which identified cystathionine gamma-lyase (CSE) as an independent marker distinguishing non-responders from responders to post-operative platinum-based chemotherapy. We aimed to identify CSE-derived metabolites responsible for chemoresistant mechanisms: gold-nanoparticle (AuN)-based surface-enhanced Raman spectroscopy (SERS) was used to enhance electromagnetic fields which enabled to visualize multiple sulfur-containing metabolites through detecting scattering light from Au-S vibration two-dimensionally. Clear cell carcinoma (CCC) who turned out less sensitive to cisplatin than serous adenocarcinoma was classified into two groups by the intensities of SERS intensities at 480 cm(-1); patients with greater intensities displayed the shorter overall survival after the debulking surgery. The SERS signals were eliminated by topically applied monobromobimane that breaks sulfane-sulfur bonds of polysulfides to result in formation of sulfodibimane which was detected at 580 cm(-1), manifesting the presence of polysulfides in cancer tissues. CCC-derived cancer cell lines in culture were resistant against cisplatin, but treatment with ambroxol, an expectorant degrading polysulfides, renders the cells CDDP-susceptible. Co-administration of ambroxol with cisplatin significantly suppressed growth of cancer xenografts in nude mice. Furthermore, polysulfides, but neither glutathione nor hypotaurine, attenuated cisplatin-induced disturbance of DNA supercoiling. Polysulfide detection by on-tissue SERS thus enables to predict prognosis of cisplatin-based chemotherapy. The current findings suggest polysulfide degradation as a stratagem unlocking cisplatin chemoresistance.", "classifications": [ { "id": "Akaike", "label": "Group Akaike", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Kazufumi", "last_name": "Honda", "name": null }, { "creator_type": "author", "first_name": "Takako", "last_name": "Hishiki", "name": null }, { "creator_type": "author", "first_name": "Sohei", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Takehiro", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Nami", "last_name": "Miura", "name": null }, { "creator_type": "author", "first_name": "Akiko", "last_name": "Kubo", "name": null }, { "creator_type": "author", "first_name": "Mai", "last_name": "Itoh", "name": null }, { "creator_type": "author", "first_name": "Wei-Yu", "last_name": "Chen", "name": null }, { "creator_type": "author", "first_name": "Masashi", "last_name": "Takano", "name": null }, { "creator_type": "author", "first_name": "Tomoyuki", "last_name": "Yoshikawa", "name": null }, { "creator_type": "author", "first_name": "Takahiro", "last_name": "Kasamatsu", "name": null }, { "creator_type": "author", "first_name": "Shinichiro", "last_name": "Sonoda", "name": null }, { "creator_type": "author", "first_name": "Hirotoshi", "last_name": "Yoshizawa", "name": null }, { "creator_type": "author", "first_name": "Seigo", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Yuichiro", "last_name": "Itai", "name": null }, { "creator_type": "author", "first_name": "Megumi", "last_name": "Shiota", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Koike", "name": null }, { "creator_type": "author", "first_name": "Masayuki", "last_name": "Naya", "name": null }, { "creator_type": "author", "first_name": "Noriyo", "last_name": "Hayakawa", "name": null }, { "creator_type": "author", "first_name": "Yoshiko", "last_name": "Naito", "name": null }, { "creator_type": "author", "first_name": "Tomomi", "last_name": "Matsuura", "name": null }, { "creator_type": "author", "first_name": "Keiko", "last_name": "Iwaisako", "name": null }, { "creator_type": "author", "first_name": "Toshihiko", "last_name": "Masui", "name": null }, { "creator_type": "author", "first_name": "Shinji", "last_name": "Uemoto", "name": null }, { "creator_type": "author", "first_name": "Kengo", "last_name": "Nagashima", "name": null }, { "creator_type": "author", "first_name": "Yoshinori", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Tomohiro", "last_name": "Sakuma", "name": null }, { "creator_type": "author", "first_name": "Osamu", "last_name": "Matsubara", "name": null }, { "creator_type": "author", "first_name": "Wilber", "last_name": "Huang", "name": null }, { "creator_type": "author", "first_name": "Tomoaki", "last_name": "Ida", "name": null }, { "creator_type": "author", "first_name": "Takaaki", "last_name": "Akaike", "name": null }, { "creator_type": "author", "first_name": "Yohei", "last_name": "Masugi", "name": null }, { "creator_type": "author", "first_name": "Michiie", "last_name": "Sakamoto", "name": null }, { "creator_type": "author", "first_name": "Tomoyasu", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Yoshinori", "last_name": "Ino", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Tsuda", "name": null }, { "creator_type": "author", "first_name": "Nobuyoshi", "last_name": "Hiraoka", "name": null }, { "creator_type": "author", "first_name": "Yasuaki", "last_name": "Kabe", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Suematsu", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.redox.2021.101926" }, "pmcid": { "normalized": "PMC8010883" }, "pmid": { "normalized": "33752108" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Antineoplastic Agents", "descriptor_ui": "D000970", "major_topic": true }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Cisplatin", "descriptor_ui": "D002945", "major_topic": false }, { "descriptor": "Drug Resistance, Neoplasm", "descriptor_ui": "D019008", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Nude", "descriptor_ui": "D008819", "major_topic": false }, { "descriptor": "Ovarian Neoplasms", "descriptor_ui": "D010051", "major_topic": true }, { "descriptor": "Spectrum Analysis, Raman", "descriptor_ui": "D013059", "major_topic": false }, { "descriptor": "Sulfides", "descriptor_ui": "D013440", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 May", "date_precision": "unknown", "issue": "", "normalized_date": null, "pages": "101926", "proceedings_title": null, "publisher": "", "title": "Redox biology", "volume": "41", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "On-tissue polysulfide visualization by surface-enhanced Raman spectroscopy benefits patients with ovarian cancer to predict post-operative chemosensitivity.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Cytokine release syndrome (CRS), occurring in more than 70% of HLA-haploidentical hematopoietic stem-cell transplantations with post-transplant cyclophosphamide (PT/CY-haplo), can lead to hemodynamic instability and worsen clinical outcomes. A calcineurin inhibitor is initiated after cyclophosphamide administration in the commonly used PT/CY regimens. Here, we conducted a phase I/II, prospective, single-center trial of PT/CY-haplo to evaluate the safety and efficacy of cyclophosphamide on days 3 and 5 along with cyclosporin and mycophenolate mofetil started from day - 1. Thirty-five adults with hematologic malignancies were enrolled. Myeloablative and reduced-intensity conditioning were used in 25 and 10 patients, respectively. Graft sources were bone marrow in 11 patients and mobilized peripheral blood stem cells in 24 patients. Disease-free survival on day 100, the primary endpoint, was 86% (95% confidence interval (CI), 69-94), which was over the predefined threshold of 50%. Unexpectedly, only 20% (95% CI, 8.4-37) of patients developed fever of > 38 degrees C early after graft infusion, all CRS grade 1, and all of which resolved just after cyclophosphamide administration. The cumulative incidences of grades II-IV acute graft-versus-host disease (GVHD), III-IV acute GVHD, and moderate-severe chronic GVHD were 23% (95% CI, 11-38), 6% (95% CI, 1-17), and 11% (95% CI, 4-25), respectively. The 3-year overall survival rate was 49% (95% CI, 31-64). Our results suggest that administration of cyclosporine and mycophenolate mofetil prior to PT/CY can reduce the frequency and severity of CRS without increasing GVHD. UMIN Clinical Trial Registry numbers: 000006631 and 000015694.", "classifications": [ { "id": "Nishikii", "label": "Group Nishikii", "parent": "Shintaku", "type": "group" }, { "id": "Shintaku", "label": "Team Shintaku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Naoki", "last_name": "Kurita", "name": null }, { "creator_type": "author", "first_name": "Tatsuhiro", "last_name": "Sakamoto", "name": null }, { "creator_type": "author", "first_name": "Takayasu", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Manabu", "last_name": "Kusakabe", "name": null }, { "creator_type": "author", "first_name": "Yasuhisa", "last_name": "Yokoyama", "name": null }, { "creator_type": "author", "first_name": "Hidekazu", "last_name": "Nishikii", "name": null }, { "creator_type": "author", "first_name": "Mamiko", "last_name": "Sakata-Yanagimoto", "name": null }, { "creator_type": "author", "first_name": "Naoshi", "last_name": "Obara", "name": null }, { "creator_type": "author", "first_name": "Yuichi", "last_name": "Hasegawa", "name": null }, { "creator_type": "author", "first_name": "Shigeru", "last_name": "Chiba", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/s00277-021-04439-6" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "33580280" } }, "mesh": [ { "descriptor": "Adolescent", "descriptor_ui": "D000293", "major_topic": false }, { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Cyclophosphamide", "descriptor_ui": "D003520", "major_topic": false }, { "descriptor": "Cyclosporine", "descriptor_ui": "D016572", "major_topic": false }, { "descriptor": "Cytokine Release Syndrome", "descriptor_ui": "D000080424", "major_topic": false }, { "descriptor": "Disease-Free Survival", "descriptor_ui": "D018572", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Graft vs Host Disease", "descriptor_ui": "D006086", "major_topic": false }, { "descriptor": "Hematopoietic Stem Cell Transplantation", "descriptor_ui": "D018380", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Immunosuppressive Agents", "descriptor_ui": "D007166", "major_topic": false }, { "descriptor": "Incidence", "descriptor_ui": "D015994", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Mycophenolic Acid", "descriptor_ui": "D009173", "major_topic": false }, { "descriptor": "Prospective Studies", "descriptor_ui": "D011446", "major_topic": false }, { "descriptor": "Transplantation, Haploidentical", "descriptor_ui": "D000075442", "major_topic": false }, { "descriptor": "Young Adult", "descriptor_ui": "D055815", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 May", "date_precision": "unknown", "issue": "5", "normalized_date": null, "pages": "1295-1301", "proceedings_title": null, "publisher": "", "title": "Annals of hematology", "volume": "100", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Early administration of cyclosporine may reduce the incidence of cytokine release syndrome after HLA-haploidentical hematopoietic stem-cell transplantation with post-transplant cyclophosphamide.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND/AIM: Programmed death-ligand 1 (PD-L1) expression on tumor cells is a predictive biomarker of programmed cell death 1 (PD-1) blockade therapy. This study sought to clarify predictors of the efficacy of nivolumab in non-small cell lung cancer (NSCLC) patients with PD-L1 expression-negative tumors. PATIENTS AND METHODS: We retrospectively reviewed the records of advanced NSCLC patients between January 2016 and April 2019, and investigated the predictive marker of nivolumab including the status of CD8(+) tumor infiltrating lymphocytes (TILs). RESULTS: A total of 70 NSCLC patients were included. Overall response rate (ORR) and progression-free survival (PFS) were better in patients with a heavy smoking history (smoking index: SI>/=600) than in those without (SI<600) [ORR: 20.6% vs. 2.8%, (p=0.02), and PFS: 2.4 months vs. 1.8 months, (p=0.04)]. A high density of CD8(+) TILs was significantly associated with a heavy smoking history (p=0.04). Conlusion: Heavy smoking history (SI>/=600), which was correlated with a large number of CD8(+) TILs, could be a predictor of the efficacy of nivolumab in NSCLC patients with PD-L1 expression-negative tumors.", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yukiko", "last_name": "Shimoda", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Masayuki", "last_name": "Shirasawa", "name": null }, { "creator_type": "author", "first_name": "Takaaki", "last_name": "Mizuno", "name": null }, { "creator_type": "author", "first_name": "Hitomi", "last_name": "Jo", "name": null }, { "creator_type": "author", "first_name": "Yuji", "last_name": "Matsumoto", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Shinno", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Okuma", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Goto", "name": null }, { "creator_type": "author", "first_name": "Hidehito", "last_name": "Horinouchi", "name": null }, { "creator_type": "author", "first_name": "Noboru", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null }, { "creator_type": "author", "first_name": "Yuichiro", "last_name": "Ohe", "name": null }, { "creator_type": "author", "first_name": "Noriko", "last_name": "Motoi", "name": null } ], "identifiers": { "doi": { "normalized": "10.21873/anticanres.15390" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "34732447" } }, "mesh": [ { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Aged, 80 and over", "descriptor_ui": "D000369", "major_topic": false }, { "descriptor": "B7-H1 Antigen", "descriptor_ui": "D060890", "major_topic": false }, { "descriptor": "Carcinoma, Non-Small-Cell Lung", "descriptor_ui": "D002289", "major_topic": false }, { "descriptor": "CD8-Positive T-Lymphocytes", "descriptor_ui": "D018414", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Immune Checkpoint Inhibitors", "descriptor_ui": "D000082082", "major_topic": false }, { "descriptor": "Lung Neoplasms", "descriptor_ui": "D008175", "major_topic": false }, { "descriptor": "Lymphocytes, Tumor-Infiltrating", "descriptor_ui": "D016246", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Nivolumab", "descriptor_ui": "D000077594", "major_topic": false }, { "descriptor": "Progression-Free Survival", "descriptor_ui": "D000077982", "major_topic": false }, { "descriptor": "Retrospective Studies", "descriptor_ui": "D012189", "major_topic": false }, { "descriptor": "Risk Assessment", "descriptor_ui": "D018570", "major_topic": false }, { "descriptor": "Risk Factors", "descriptor_ui": "D012307", "major_topic": false }, { "descriptor": "Smokers", "descriptor_ui": "D000074285", "major_topic": true }, { "descriptor": "Smoking", "descriptor_ui": "D012907", "major_topic": false }, { "descriptor": "Time Factors", "descriptor_ui": "D013997", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Nov", "date_precision": "unknown", "issue": "11", "normalized_date": null, "pages": "5739-5747", "proceedings_title": null, "publisher": "", "title": "Anticancer research", "volume": "41", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Smoking History Predicts High Presence of TILs and Efficacy of PD-1 Blockade in PD-L1 Expression-negative Non-small Cell Lung Cancer Patients.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND AND PURPOSE: Ionising radiation causes mutations in the genomes of tumour cells and serves as a potent treatment for cancer. However, the mutation signatures in the cancer genome following ionising radiation have not been documented. MATERIALS AND METHODS: We established an in vitro experimental system to analyse the presence of de novo mutations in the cancer genome of irradiated (60 Gy/20 fr/4 weeks) oesophageal cancer cell lines. Subsequently, we performed whole-genome, chromatin immunoprecipitation, and RNA sequencing using untreated and irradiated samples to assess the damage to the genome caused by radiation and understand the underlying mechanism. RESULTS: The irradiated cancer cells exhibited hotspots for the de novo 8502-12966 single nucleotide variants and 954-1,331 indels on the chromosome. These single nucleotide variants primarily originated from double-stranded break repair errors, as determined using mutation signature analysis. The hotspots partially overlapped with the sites of H3K9 trimethylation, which are regions characterised by a weak capacity for double-stranded break repair. CONCLUSION: This study highlights the signature and underlying mechanism of radiation on the cancer genome.", "classifications": [ { "id": "Hamamoto", "label": "Group Hamamoto", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Shun-Ichiro", "last_name": "Kageyama", "name": null }, { "creator_type": "author", "first_name": "Junyan", "last_name": "Du", "name": null }, { "creator_type": "author", "first_name": "Syuzo", "last_name": "Kaneko", "name": null }, { "creator_type": "author", "first_name": "Ryuji", "last_name": "Hamamoto", "name": null }, { "creator_type": "author", "first_name": "Shigeo", "last_name": "Yamaguchi", "name": null }, { "creator_type": "author", "first_name": "Riu", "last_name": "Yamashita", "name": null }, { "creator_type": "author", "first_name": "Masayuki", "last_name": "Okumura", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Motegi", "name": null }, { "creator_type": "author", "first_name": "Hidehiro", "last_name": "Hojo", "name": null }, { "creator_type": "author", "first_name": "Masaki", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Katsuya", "last_name": "Tsuchihara", "name": null }, { "creator_type": "author", "first_name": "Tetsuo", "last_name": "Akimoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.radonc.2020.10.020" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "33075393" } }, "mesh": [ { "descriptor": "DNA Repair", "descriptor_ui": "D004260", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": false }, { "descriptor": "Neoplasms", "descriptor_ui": "D009369", "major_topic": true }, { "descriptor": "Radiation, Ionizing", "descriptor_ui": "D011839", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Feb", "date_precision": "unknown", "issue": "", "normalized_date": null, "pages": "10-16", "proceedings_title": null, "publisher": "", "title": "Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology", "volume": "155", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Identification of the mutation signature of the cancer genome caused by irradiation.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "", "classifications": [ { "id": "Eiraku", "label": "Group Eiraku", "parent": "Eiraku", "type": "group" }, { "id": "Eiraku", "label": "Team Eiraku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Makoto", "last_name": "Ikeya", "name": null }, { "creator_type": "author", "first_name": "Yayoi", "last_name": "Toyooka", "name": null }, { "creator_type": "author", "first_name": "Mototsugu", "last_name": "Eiraku", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/dgd.12720" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "33666222" } }, "mesh": [ { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Developmental Biology", "descriptor_ui": "D015509", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Pluripotent Stem Cells", "descriptor_ui": "D039904", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Feb", "date_precision": "unknown", "issue": "2", "normalized_date": null, "pages": "103", "proceedings_title": null, "publisher": "", "title": "Development, growth & differentiation", "volume": "63", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Pluripotent stem cells in developmental biology (part 2).", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "", "classifications": [ { "id": "Onami", "label": "Group Onami", "parent": "Fujiwara", "type": "group" }, { "id": "Fujiwara", "label": "Team Fujiwara", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Jason R.", "last_name": "Swedlow", "name": null }, { "creator_type": "author", "first_name": "Pasi", "last_name": "Kankaanpaa", "name": null }, { "creator_type": "author", "first_name": "Ugis", "last_name": "Sarkans", "name": null }, { "creator_type": "author", "first_name": "Wojtek", "last_name": "Goscinski", "name": null }, { "creator_type": "author", "first_name": "Graham", "last_name": "Galloway", "name": null }, { "creator_type": "author", "first_name": "Leonel", "last_name": "Malacrida", "name": null }, { "creator_type": "author", "first_name": "Ryan P.", "last_name": "Sullivan", "name": null }, { "creator_type": "author", "first_name": "Steffen", "last_name": "Hartel", "name": null }, { "creator_type": "author", "first_name": "Claire M.", "last_name": "Brown", "name": null }, { "creator_type": "author", "first_name": "Christopher", "last_name": "Wood", "name": null }, { "creator_type": "author", "first_name": "Antje", "last_name": "Keppler", "name": null }, { "creator_type": "author", "first_name": "Federica", "last_name": "Paina", "name": null }, { "creator_type": "author", "first_name": "Ben", "last_name": "Loos", "name": null }, { "creator_type": "author", "first_name": "Sara", "last_name": "Zullino", "name": null }, { "creator_type": "author", "first_name": "Dario Livio", "last_name": "Longo", "name": null }, { "creator_type": "author", "first_name": "Silvio", "last_name": "Aime", "name": null }, { "creator_type": "author", "first_name": "Shuichi", "last_name": "Onami", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41592-021-01113-7" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "33948027" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Artificial Intelligence", "descriptor_ui": "D001185", "major_topic": false }, { "descriptor": "Computational Biology", "descriptor_ui": "D019295", "major_topic": false }, { "descriptor": "Databases, Factual", "descriptor_ui": "D016208", "major_topic": false }, { "descriptor": "Diagnostic Imaging", "descriptor_ui": "D003952", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Image Processing, Computer-Assisted", "descriptor_ui": "D007091", "major_topic": false }, { "descriptor": "Information Storage and Retrieval", "descriptor_ui": "D016247", "major_topic": false }, { "descriptor": "Metadata", "descriptor_ui": "D000071253", "major_topic": false }, { "descriptor": "Microscopy", "descriptor_ui": "D008853", "major_topic": false }, { "descriptor": "Proteomics", "descriptor_ui": "D040901", "major_topic": false }, { "descriptor": "Societies, Scientific", "descriptor_ui": "D012958", "major_topic": false }, { "descriptor": "Software", "descriptor_ui": "D012984", "major_topic": false }, { "descriptor": "Spectrum Analysis, Raman", "descriptor_ui": "D013059", "major_topic": false }, { "descriptor": "User-Computer Interface", "descriptor_ui": "D014584", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Dec", "date_precision": "unknown", "issue": "12", "normalized_date": null, "pages": "1440-1446", "proceedings_title": null, "publisher": "", "title": "Nature methods", "volume": "18", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "A global view of standards for open image data formats and repositories.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "What particular mechanical properties can be expected for materials composed of interlocked backbones has been a long-standing issue in materials science since the first reports on polycatenane and polyrotaxane in the 1970s(1-3). Here we report a three-dimensional porous metal-organic crystal, which is exceptional in that its warps and wefts are connected only by catenation. This porous crystal is composed of a tetragonal lattice and dynamically changes its geometry upon guest molecule release, uptake and exchange, and also upon temperature variation even in a low temperature range. We indented(4) the crystal along its a/b axes and obtained the Young's moduli of 1.77 +/- 0.16 GPa in N,N-dimethylformamide and 1.63 +/- 0.13 GPa in tetrahydrofuran, which are the lowest among those reported so far for porous metal-organic crystals(5). To our surprise, hydrostatic compression showed that this elastic porous crystal was the most deformable along its c axis, where 5% contraction occurred without structural deterioration upon compression up to 0.88 GPa. The crystal structure obtained at 0.46 GPa showed that the catenated macrocycles move translationally upon contraction. We anticipate our mechanically interlocked molecule-based design to be a starting point for the development of porous materials with exotic mechanical properties. For example, squeezable porous crystals that may address an essential difficulty in realizing both high abilities of guest uptake and release are on the horizon.", "classifications": [ { "id": "Hijikata", "label": "Group Hijikata", "parent": "Tsuchiya", "type": "group" }, { "id": "Tsuchiya", "label": "Team Tsuchiya", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Wenjing", "last_name": "Meng", "name": null }, { "creator_type": "author", "first_name": "Shun", "last_name": "Kondo", "name": null }, { "creator_type": "author", "first_name": "Takuji", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Kazuki", "last_name": "Komatsu", "name": null }, { "creator_type": "author", "first_name": "Jenny", "last_name": "Pirillo", "name": null }, { "creator_type": "author", "first_name": "Yuh", "last_name": "Hijikata", "name": null }, { "creator_type": "author", "first_name": "Yuichi", "last_name": "Ikuhara", "name": null }, { "creator_type": "author", "first_name": "Takuzo", "last_name": "Aida", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Sato", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41586-021-03880-x" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "34646002" } }, "mesh": [], "publication": { "conference_name": null, "date": "2021 Oct", "date_precision": "unknown", "issue": "7880", "normalized_date": null, "pages": "298-303", "proceedings_title": null, "publisher": "", "title": "Nature", "volume": "598", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "An elastic metal-organic crystal with a densely catenated backbone.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Artificial intelligence (AI) is being increasingly adopted in medical research and applications. Medical AI devices have continuously been approved by the Food and Drug Administration in the United States and the responsible institutions of other countries. Ultrasound (US) imaging is commonly used in an extensive range of medical fields. However, AI-based US imaging analysis and its clinical implementation have not progressed steadily compared to other medical imaging modalities. The characteristic issues of US imaging owing to its manual operation and acoustic shadows cause difficulties in image quality control. In this review, we would like to introduce the global trends of medical AI research in US imaging from both clinical and basic perspectives. We also discuss US image preprocessing, ingenious algorithms that are suitable for US imaging analysis, AI explainability for obtaining informed consent, the approval process of medical AI devices, and future perspectives towards the clinical application of AI-based US diagnostic support technologies.", "classifications": [ { "id": "Hamamoto", "label": "Group Hamamoto", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Masaaki", "last_name": "Komatsu", "name": null }, { "creator_type": "author", "first_name": "Akira", "last_name": "Sakai", "name": null }, { "creator_type": "author", "first_name": "Ai", "last_name": "Dozen", "name": null }, { "creator_type": "author", "first_name": "Kanto", "last_name": "Shozu", "name": null }, { "creator_type": "author", "first_name": "Suguru", "last_name": "Yasutomi", "name": null }, { "creator_type": "author", "first_name": "Hidenori", "last_name": "Machino", "name": null }, { "creator_type": "author", "first_name": "Ken", "last_name": "Asada", "name": null }, { "creator_type": "author", "first_name": "Syuzo", "last_name": "Kaneko", "name": null }, { "creator_type": "author", "first_name": "Ryuji", "last_name": "Hamamoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.3390/biomedicines9070720" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "34201827" } }, "mesh": [], "publication": { "conference_name": null, "date": "2021 Jul", "date_precision": "unknown", "issue": "7", "normalized_date": null, "pages": "", "proceedings_title": null, "publisher": "", "title": "Biomedicines", "volume": "9", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Towards Clinical Application of Artificial Intelligence in Ultrasound Imaging.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "", "classifications": [ { "id": "Nishida", "label": "Group Nishida", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Tomohiro", "last_name": "Sawa", "name": null }, { "creator_type": "author", "first_name": "Motohiro", "last_name": "Nishida", "name": null } ], "identifiers": { "doi": { "normalized": "10.3164/jcbn.68-1-intro" }, "pmcid": { "normalized": "PMC7844663" }, "pmid": { "normalized": "33536705" } }, "mesh": [], "publication": { "conference_name": null, "date": "2021 Jan", "date_precision": "unknown", "issue": "1", "normalized_date": null, "pages": "4", "proceedings_title": null, "publisher": "", "title": "Journal of clinical biochemistry and nutrition", "volume": "68", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Introduction to serial reviews: Recent developments in research of reactive sulfur species.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "This work shows that GATA transcription factors transduce the BMP signaling and, with SOX17 and TFAP2C, induce the human germ-cell fate, delineating the mechanism for human germ-cell specification.", "classifications": [ { "id": "Yamamoto", "label": "Group Yamamoto", "parent": "Toyoshima", "type": "group" }, { "id": "Toyoshima", "label": "Team Toyoshima", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yoji", "last_name": "Kojima", "name": null }, { "creator_type": "author", "first_name": "Chika", "last_name": "Yamashiro", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Murase", "name": null }, { "creator_type": "author", "first_name": "Yukihiro", "last_name": "Yabuta", "name": null }, { "creator_type": "author", "first_name": "Ikuhiro", "last_name": "Okamoto", "name": null }, { "creator_type": "author", "first_name": "Chizuru", "last_name": "Iwatani", "name": null }, { "creator_type": "author", "first_name": "Hideaki", "last_name": "Tsuchiya", "name": null }, { "creator_type": "author", "first_name": "Masataka", "last_name": "Nakaya", "name": null }, { "creator_type": "author", "first_name": "Tomoyuki", "last_name": "Tsukiyama", "name": null }, { "creator_type": "author", "first_name": "Tomonori", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Mitinori", "last_name": "Saitou", "name": null } ], "identifiers": { "doi": { "normalized": "10.26508/lsa.202000974" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "33608411" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Cell Lineage", "descriptor_ui": "D019070", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "GATA Transcription Factors", "descriptor_ui": "D050980", "major_topic": false }, { "descriptor": "Germ Cells", "descriptor_ui": "D005854", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Induced Pluripotent Stem Cells", "descriptor_ui": "D057026", "major_topic": false }, { "descriptor": "Macaca fascicularis", "descriptor_ui": "D008252", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred ICR", "descriptor_ui": "D008813", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "SOXF Transcription Factors", "descriptor_ui": "D055760", "major_topic": false }, { "descriptor": "Transcription Factor AP-2", "descriptor_ui": "D050656", "major_topic": false }, { "descriptor": "Transcription Factors", "descriptor_ui": "D014157", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 May", "date_precision": "unknown", "issue": "5", "normalized_date": null, "pages": "", "proceedings_title": null, "publisher": "", "title": "Life Science Alliance", "volume": "4", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "GATA transcription factors, SOX17 and TFAP2C, drive the human germ-cell specification program.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Patients with non-small cell lung cancer (NSCLC) harboring ROS proto-oncogene 1 (ROS1) gene rearrangements show dramatic response to the tyrosine kinase inhibitor (TKI) crizotinib. Current best practice guidelines recommend that all advanced stage non-squamous NSCLC patients be also tested for ROS1 gene rearrangements. Several studies have suggested that ROS1 immunohistochemistry (IHC) using the D4D6 antibody may be used to screen for ROS1 fusion positive lung cancers, with assays showing high sensitivity but moderate to high specificity. A break apart fluorescence in situ hybridization (FISH) test is then used to confirm the presence of ROS1 gene rearrangement. The goal of Canadian ROS1 (CROS) study was to harmonize ROS1 laboratory developed testing (LDT) by using IHC and FISH assays to detect ROS1 rearranged lung cancers across Canadian pathology laboratories. Cell lines expressing different levels of ROS1 (high, low, none) were used to calibrate IHC protocols after which participating laboratories ran the calibrated protocols on a reference set of 24 NSCLC cases (9 ROS1 rearranged tumors and 15 ROS1 non-rearranged tumors as determined by FISH). Results were compared using a centralized readout. The stained slides were evaluated for the cellular localization of staining, intensity of staining, the presence of staining in non-tumor cells, the presence of non-specific staining (e.g. necrosis, extracellular mater, other) and the percent positive cells. H-score was also determined for each tumor. Analytical sensitivity and specificity harmonization was achieved by using low limit of detection (LOD) as either any positivity in the U118 cell line or H-score of 200 with the HCC78 cell line. An overall diagnostic sensitivity and specificity of up to 100% and 99% respectively was achieved for ROS1 IHC testing (relative to FISH) using an adjusted H-score readout on the reference cases. This study confirms that LDT ROS1 IHC assays can be highly sensitive and specific for detection of ROS1 rearrangements in NSCLC. As NSCLC can demonstrate ROS1 IHC positivity in FISH-negative cases, the degree of the specificity of the IHC assay, especially in highly sensitive protocols, is mostly dependent on the readout cut-off threshold. As ROS1 IHC is a screening assay for a rare rearrangements in NSCLC, we recommend adjustment of the readout threshold in order to balance specificity, rather than decreasing the overall analytical and diagnostic sensitivity of the protocols.", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Carol C.", "last_name": "Cheung", "name": null }, { "creator_type": "author", "first_name": "Adam C.", "last_name": "Smith", "name": null }, { "creator_type": "author", "first_name": "Roula", "last_name": "Albadine", "name": null }, { "creator_type": "author", "first_name": "Gilbert", "last_name": "Bigras", "name": null }, { "creator_type": "author", "first_name": "Anna", "last_name": "Bojarski", "name": null }, { "creator_type": "author", "first_name": "Christian", "last_name": "Couture", "name": null }, { "creator_type": "author", "first_name": "Jean-Claude", "last_name": "Cutz", "name": null }, { "creator_type": "author", "first_name": "Weei-Yuan", "last_name": "Huang", "name": null }, { "creator_type": "author", "first_name": "Diana", "last_name": "Ionescu", "name": null }, { "creator_type": "author", "first_name": "Doha", "last_name": "Itani", "name": null }, { "creator_type": "author", "first_name": "Iyare", "last_name": "Izevbaye", "name": null }, { "creator_type": "author", "first_name": "Aly", "last_name": "Karsan", "name": null }, { "creator_type": "author", "first_name": "Margaret M.", "last_name": "Kelly", "name": null }, { "creator_type": "author", "first_name": "Joan", "last_name": "Knoll", "name": null }, { "creator_type": "author", "first_name": "Keith", "last_name": "Kwan", "name": null }, { "creator_type": "author", "first_name": "Michel R.", "last_name": "Nasr", "name": null }, { "creator_type": "author", "first_name": "Gefei", "last_name": "Qing", "name": null }, { "creator_type": "author", "first_name": "Fariboz", "last_name": "Rashid-Kolvear", "name": null }, { "creator_type": "author", "first_name": "Harmanjatinder S.", "last_name": "Sekhon", "name": null }, { "creator_type": "author", "first_name": "Alan", "last_name": "Spatz", "name": null }, { "creator_type": "author", "first_name": "Tracy", "last_name": "Stockley", "name": null }, { "creator_type": "author", "first_name": "Danh", "last_name": "Tran-Thanh", "name": null }, { "creator_type": "author", "first_name": "Tracy", "last_name": "Tucker", "name": null }, { "creator_type": "author", "first_name": "Ranjit", "last_name": "Waghray", "name": null }, { "creator_type": "author", "first_name": "Hangjun", "last_name": "Wang", "name": null }, { "creator_type": "author", "first_name": "Zhaolin", "last_name": "Xu", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null }, { "creator_type": "author", "first_name": "Emina E.", "last_name": "Torlakovic", "name": null }, { "creator_type": "author", "first_name": "Ming-Sound", "last_name": "Tsao", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.lungcan.2021.08.003" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "34509095" } }, "mesh": [ { "descriptor": "Canada", "descriptor_ui": "D002170", "major_topic": false }, { "descriptor": "Carcinoma, Non-Small-Cell Lung", "descriptor_ui": "D002289", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "In Situ Hybridization, Fluorescence", "descriptor_ui": "D017404", "major_topic": false }, { "descriptor": "Lung Neoplasms", "descriptor_ui": "D008175", "major_topic": true }, { "descriptor": "Protein-Tyrosine Kinases", "descriptor_ui": "D011505", "major_topic": false }, { "descriptor": "Proto-Oncogene Mas", "descriptor_ui": "D000090063", "major_topic": false }, { "descriptor": "Proto-Oncogene Proteins", "descriptor_ui": "D011518", "major_topic": false }, { "descriptor": "Proto-Oncogenes", "descriptor_ui": "D011519", "major_topic": false }, { "descriptor": "Reactive Oxygen Species", "descriptor_ui": "D017382", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Oct", "date_precision": "unknown", "issue": "", "normalized_date": null, "pages": "127-135", "proceedings_title": null, "publisher": "", "title": "Lung cancer (Amsterdam, Netherlands)", "volume": "160", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Canadian ROS proto-oncogene 1 study (CROS) for multi-institutional implementation of ROS1 testing in non-small cell lung cancer.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Amino acids are indispensable nutrients for both normal and cancer cells. Cancer cells are unable to synthesize essential amino acids as well as some non-essential amino acids adequately to support rapid proliferation, and must take up amino acids from the surroundings. To meet the increased demand for the amino acid needed for proliferation, high levels of amino acid transporters are expressed on the surface of cancer cells. Cancer cells utilize amino acids to synthesize proteins and nucleotides, as well as to obtain energy. In addition, amino acids are known to play pathological roles in cancer cells. Interestingly, breast cancer cells limit the use of amino acids for cell proliferation based on amino acid availability, which depends on estrogen receptor status. Here, we present a summarized literature review of novel amino acid functions in cancer cells. This review organizes the available knowledge on 2 amino acid transporters, SLC7A5 and SLC7A11, which are considered essential for breast cancer cell growth in a cell-dependent manner. In particular, we propose the glutamine recycling model to clarify the mechanism underlying aberrant SLC7A5 activation. Finally, we overview the pathological significances of SLC7A5 and SLC7A11 in cancer tissues.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yasuhiro", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/cas.15006" }, "pmcid": { "normalized": "PMC8353895" }, "pmid": { "normalized": "34091991" } }, "mesh": [ { "descriptor": "Amino Acid Transport System y+", "descriptor_ui": "D027182", "major_topic": false }, { "descriptor": "Amino Acids", "descriptor_ui": "D000596", "major_topic": false }, { "descriptor": "Antineoplastic Agents", "descriptor_ui": "D000970", "major_topic": false }, { "descriptor": "Breast Neoplasms", "descriptor_ui": "D001943", "major_topic": false }, { "descriptor": "Cell Proliferation", "descriptor_ui": "D049109", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Gene Expression Regulation, Neoplastic", "descriptor_ui": "D015972", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Large Neutral Amino Acid-Transporter 1", "descriptor_ui": "D027283", "major_topic": false }, { "descriptor": "Molecular Targeted Therapy", "descriptor_ui": "D058990", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Aug", "date_precision": "unknown", "issue": "8", "normalized_date": null, "pages": "2958-2965", "proceedings_title": null, "publisher": "", "title": "Cancer science", "volume": "112", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Amino acid transporters as emerging therapeutic targets in cancer.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "In animal embryos, gene regulatory networks control the dynamics of gene expression in cells and coordinate such dynamics among cells. In ascidian embryos, gene expression dynamics have been dissected at the single-cell resolution. Here, we revealed mathematical functions that represent the regulatory logics of all regulatory genes expressed at the 32-cell stage when the germ layers are largely specified. These functions collectively explain the entire mechanism by which gene expression dynamics are controlled coordinately in early embryos. We found that regulatory functions for genes expressed in each of the specific lineages contain a common core regulatory mechanism. Last, we showed that the expression of the regulatory genes became reproducible by calculation and controllable by experimental manipulations. Thus, these regulatory functions represent an architectural design for the germ layer specification of this chordate and provide a platform for simulations and experiments to understand the operating principles of gene regulatory networks.", "classifications": [ { "id": "JPMJCR1922", "label": "JPMJCR1922", "researcher": "Mototsugu Eiraku", "type": "grant" }, { "id": "Eiraku", "label": "Group Eiraku", "parent": "Eiraku", "type": "group" }, { "id": "Mochizuki", "label": "Group Mochizuki", "parent": "Eiraku", "type": "group" }, { "id": "Eiraku", "label": "Team Eiraku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Miki", "last_name": "Tokuoka", "name": null }, { "creator_type": "author", "first_name": "Kazuki", "last_name": "Maeda", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Mochizuki", "name": null }, { "creator_type": "author", "first_name": "Yutaka", "last_name": "Satou", "name": null } ], "identifiers": { "doi": { "normalized": "10.1126/sciadv.abf8210" }, "pmcid": { "normalized": "PMC8189585" }, "pmid": { "normalized": "34108211" } }, "mesh": [], "publication": { "conference_name": null, "date": "2021 Jun", "date_precision": "unknown", "issue": "24", "normalized_date": null, "pages": "eabf8210", "proceedings_title": null, "publisher": "", "title": "Science advances", "volume": "7", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "The gene regulatory system for specifying germ layers in early embryos of the simple chordate.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The spiral arrangement (phyllotaxis) of leaves is a shared morphology in land plants, and exhibits diversity constrained to the Fibonacci sequence. Phyllotaxis in vascular plants is produced at a multicellular meristem, whereas bryophyte phyllotaxis emerges from a single apical stem cell (AC) that is embedded in a growing tip of the gametophyte. An AC is asymmetrically divided into itself and a single 'merophyte', producing a future leaf and a portion of the stem. Although it has been suggested that the arrangement of merophytes is regulated by a rotation of the division plane of an AC, the quantitative description of the merophyte arrangement and its regulatory mechanism remain unclear. To clarify them, we examined three moss species, Tetraphis pellucida, Physcomitrium patens, and Niphotrichum japonicum, which exhibit 1/3, 2/5, and 3/8 spiral phyllotaxis, respectively. We measured the angle between the centroids of adjacent merophytes relative to the AC centroid on cross-transverse sections. At the outer merophytes, this divergence angle converged to nearly 120[Formula: see text] in T. pellucida, 136[Formula: see text] in N. japonicum, and 141[Formula: see text] in P. patens, which was nearly consistent with phyllotaxis, whereas the divergence angle deviated from the converged angle at the inner merophytes near an AC. A mathematical model, which assumes scaling growth of AC and merophytes and a constant angle of division plane rotation, quantitatively reproduced the sequence of the divergence angles. This model showed that successive relocations of the centroid position of an AC upon its division inevitably result in the transient deviation of the divergence angle. As a result, the converged divergence angle was equal to the rotation angle, predicting that the latter is a major regulator of the spiral phyllotaxis diversity in mosses.", "classifications": [ { "id": "Fujimoto", "label": "Group Fujimoto", "parent": "Ueda", "type": "group" }, { "id": "Ueda", "label": "Team Ueda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Naoya", "last_name": "Kamamoto", "name": null }, { "creator_type": "author", "first_name": "Taishi", "last_name": "Tano", "name": null }, { "creator_type": "author", "first_name": "Koichi", "last_name": "Fujimoto", "name": null }, { "creator_type": "author", "first_name": "Masaki", "last_name": "Shimamura", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/s10265-021-01298-0" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "33877466" } }, "mesh": [ { "descriptor": "Bryophyta", "descriptor_ui": "D044002", "major_topic": true }, { "descriptor": "Cell Division", "descriptor_ui": "D002455", "major_topic": false }, { "descriptor": "Meristem", "descriptor_ui": "D018519", "major_topic": false }, { "descriptor": "Models, Biological", "descriptor_ui": "D008954", "major_topic": false }, { "descriptor": "Rotation", "descriptor_ui": "D012399", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 May", "date_precision": "unknown", "issue": "3", "normalized_date": null, "pages": "457-473", "proceedings_title": null, "publisher": "", "title": "Journal of plant research", "volume": "134", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Rotation angle of stem cell division plane controls spiral phyllotaxis in mosses.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The use of patient‐derived xenografts (PDXs) has recently attracted attention as a drug discovery platform with a high predictive clinical efficacy and a preserved tumor heterogeneity. Given the racial differences in genetic variations, it would be desirable to establish a PDX library from Japanese cancer patients on a large scale. We thus tried to construct the Japanese PDX (J‐PDX) library with a detailed clinical information for further clinical utilization. Between August 2018 and May 2020, a total of 1126 cancer specimens from 1079 patients were obtained at the National Cancer Center Hospital and National Cancer Center Hospital East, Japan, and were immediately transplanted to immunodeficient mice at the National Cancer Center Research Institute. A total of 298 cross‐cancer PDXs were successfully established. The time to engraftment varied greatly by cancer subtypes, especially in the first passage. The engraftment rate was strongly affected by the clinical stage and survival time of the original patients. Approximately 1 year was needed from tumor collection to the time when coclinical trials were conducted to test the clinical utility. The 1‐year survival rates of the patients who were involved in establishing the PDX differed significantly, from 95.6% for colorectal cancer to 56.3% for lung cancer. The J‐PDX library consisting of a wide range of cancer subtypes has been successfully established as a platform for drug discovery and development in Japan. When conducting coclinical trials, it is necessary to consider the target cancer type, stage, and engraftment rate in light of this report.", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Shigehiro", "last_name": "Yagishita", "name": null }, { "creator_type": "author", "first_name": "Ken", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Mami", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Toshio", "last_name": "Imai", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Kuwata", "name": null }, { "creator_type": "author", "first_name": "Mikiko", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Ochiai", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Ohtsu", "name": null }, { "creator_type": "author", "first_name": "Kazuaki", "last_name": "Shimada", "name": null }, { "creator_type": "author", "first_name": "Toshirou", "last_name": "Nishida", "name": null }, { "creator_type": "author", "first_name": "Akinobu", "last_name": "Hamada", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Mano", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/cas.14899" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "33759313" } }, "mesh": [ { "descriptor": "Adolescent", "descriptor_ui": "D000293", "major_topic": false }, { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Aged, 80 and over", "descriptor_ui": "D000369", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Child", "descriptor_ui": "D002648", "major_topic": false }, { "descriptor": "Child, Preschool", "descriptor_ui": "D002675", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Japan", "descriptor_ui": "D007564", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Neoplasm Staging", "descriptor_ui": "D009367", "major_topic": false }, { "descriptor": "Neoplasm Transplantation", "descriptor_ui": "D009368", "major_topic": false }, { "descriptor": "Neoplasms", "descriptor_ui": "D009369", "major_topic": false }, { "descriptor": "Organ Specificity", "descriptor_ui": "D009928", "major_topic": false }, { "descriptor": "Patient-Specific Modeling", "descriptor_ui": "D066230", "major_topic": false }, { "descriptor": "Young Adult", "descriptor_ui": "D055815", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Jun", "date_precision": "unknown", "issue": "6", "normalized_date": null, "pages": "2454-2466", "proceedings_title": null, "publisher": "", "title": "Cancer Science", "volume": "112", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Characterization of the large‐scale Japanese patient‐derived xenograft (J‐PDX) library.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Depolarization of circularly polarized light scattered from biological tissues depends on structural changes in cell nuclei, which can provide valuable information for differentiating cancer tissues concealed in healthy tissues. In this study, we experimentally verified the possibility of cancer identification using scattering of circularly polarized light. We investigated the polarization of light scattered from a sliced biological tissue with various optical configurations. A significant difference between circular polarizations of light scattered from cancerous and healthy tissues is observed, which is sufficient to distinguish a cancerous region. The line-scanning experiments along a region incorporating healthy and cancerous parts indicate step-like behaviors in the degree of circular polarization corresponding to the state of tissues, whether cancerous or normal. An oblique and perpendicular incidence induces different resolutions for identifying cancerous tissues, which indicates that the optical arrangement can be selected according to the priority of resolution.", "classifications": [ { "id": "Kuchimaru", "label": "Group Kuchimaru", "parent": "Shintaku", "type": "group" }, { "id": "Shintaku", "label": "Team Shintaku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Nozomi", "last_name": "Nishizawa", "name": null }, { "creator_type": "author", "first_name": "Bassam", "last_name": "Al-Qadi", "name": null }, { "creator_type": "author", "first_name": "Takahiro", "last_name": "Kuchimaru", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/jbio.202000380" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "33295146" } }, "mesh": [ { "descriptor": "Cell Nucleus", "descriptor_ui": "D002467", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Neoplasms", "descriptor_ui": "D009369", "major_topic": true }, { "descriptor": "Scattering, Radiation", "descriptor_ui": "D012542", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Mar", "date_precision": "unknown", "issue": "3", "normalized_date": null, "pages": "e202000380", "proceedings_title": null, "publisher": "", "title": "Journal of biophotonics", "volume": "14", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Angular optimization for cancer identification with circularly polarized light.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: Recent studies highlighted the clinicopathological heterogeneity of non-ampullary duodenal adenomas and adenocarcinomas, but the detailed process of the malignant transformation remains unclear. METHODS: We analyzed 144 adenomas and 54 adenocarcinomas of the non-ampullary duodenum for immunohistochemical phenotypes, genetic alterations, and mismatch repair (MMR) status to probe their histogenetic relationship. RESULTS: The median ages of patients with adenoma and adenocarcinoma were the same (66 years). Adenomas were histologically classified as intestinal-type adenoma (n = 124), pyloric gland adenoma (PGA, n = 10), gastric-type adenoma, not otherwise specified (n = 9), and foveolar-type adenoma (n = 1). Protein-truncating APC mutations were highly frequent in adenomas (85%), with the highest prevalence in intestinal-type adenomas (89%), but rare in adenocarcinomas (9%; P = 2.1 x 10(-23)). Close associations between phenotypic marker expression and genetic alterations were observed in adenomas, but not in adenocarcinomas, excluding the common association between GNAS mutations and MUC5AC expression. MMR deficiency was more frequent in adenocarcinomas (20%) than in adenomas (1%; P = 2.6 x 10(-6)). One MMR-deficient adenoma and three MMR-deficient adenocarcinomas occurred in patients with Lynch syndrome. Additionally, three other patients with an MMR-deficient adenocarcinoma fulfilled the revised Bethesda criteria. CONCLUSION: The discrepant APC mutation frequency between adenomas and adenocarcinomas suggests that APC-mutated adenomas, which constitute the large majority of non-ampullary duodenal adenomas, are less prone to malignant transformation. Non-ampullary duodenal adenocarcinomas frequently exhibit MMR deficiency and should be subject to MMR testing to determine appropriate clinical management, including the identification of patients with Lynch syndrome.", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Kenichi", "last_name": "Ishizu", "name": null }, { "creator_type": "author", "first_name": "Taiki", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Tomoaki", "last_name": "Naka", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null }, { "creator_type": "author", "first_name": "Motohiro", "last_name": "Kojima", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Kuwata", "name": null }, { "creator_type": "author", "first_name": "Satoru", "last_name": "Nonaka", "name": null }, { "creator_type": "author", "first_name": "Ichiro", "last_name": "Oda", "name": null }, { "creator_type": "author", "first_name": "Minoru", "last_name": "Esaki", "name": null }, { "creator_type": "author", "first_name": "Masashi", "last_name": "Kudo", "name": null }, { "creator_type": "author", "first_name": "Naoto", "last_name": "Gotohda", "name": null }, { "creator_type": "author", "first_name": "Teruhiko", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Takaki", "last_name": "Yoshikawa", "name": null }, { "creator_type": "author", "first_name": "Shigeki", "last_name": "Sekine", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/s00535-021-01823-x" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "34514550" } }, "mesh": [ { "descriptor": "Adenocarcinoma", "descriptor_ui": "D000230", "major_topic": false }, { "descriptor": "Adenomatous Polyposis Coli Protein", "descriptor_ui": "D025601", "major_topic": false }, { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Duodenal Neoplasms", "descriptor_ui": "D004379", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Japan", "descriptor_ui": "D007564", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Nov", "date_precision": "unknown", "issue": "11", "normalized_date": null, "pages": "988-998", "proceedings_title": null, "publisher": "", "title": "Journal of gastroenterology", "volume": "56", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "APC mutations are common in adenomas but infrequent in adenocarcinomas of the non-ampullary duodenum.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "In medical imaging, the characteristics purely derived from a disease should reflect the extent to which abnormal findings deviate from the normal features. Indeed, physicians often need corresponding images without abnormal findings of interest or, conversely, images that contain similar abnormal findings regardless of normal anatomical context. This is called comparative diagnostic reading of medical images, which is essential for a correct diagnosis. To support comparative diagnostic reading, content-based image retrieval (CBIR) that can selectively utilize normal and abnormal features in medical images as two separable semantic components will be useful. In this study, we propose a neural network architecture to decompose the semantic components of medical images into two latent codes: normal anatomy code and abnormal anatomy code. The normal anatomy code represents counterfactual normal anatomies that should have existed if the sample is healthy, whereas the abnormal anatomy code attributes to abnormal changes that reflect deviation from the normal baseline. By calculating the similarity based on either normal or abnormal anatomy codes or the combination of the two codes, our algorithm can retrieve images according to the selected semantic component from a dataset consisting of brain magnetic resonance images of gliomas. Moreover, it can utilize a synthetic query vector combining normal and abnormal anatomy codes from two different query images. To evaluate whether the retrieved images are acquired according to the targeted semantic component, the overlap of the ground-truth labels is calculated as metrics of the semantic consistency. Our algorithm provides a flexible CBIR framework by handling the decomposed features with qualitatively and quantitatively remarkable results.", "classifications": [ { "id": "Hamamoto", "label": "Group Hamamoto", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Kazuma", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Ryuichiro", "last_name": "Hataya", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Kurose", "name": null }, { "creator_type": "author", "first_name": "Mototaka", "last_name": "Miyake", "name": null }, { "creator_type": "author", "first_name": "Masamichi", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Akiko", "last_name": "Nakagawa", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Harada", "name": null }, { "creator_type": "author", "first_name": "Ryuji", "last_name": "Hamamoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.media.2021.102227" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "34543911" } }, "mesh": [ { "descriptor": "Algorithms", "descriptor_ui": "D000465", "major_topic": false }, { "descriptor": "Glioma", "descriptor_ui": "D005910", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Information Storage and Retrieval", "descriptor_ui": "D016247", "major_topic": true }, { "descriptor": "Magnetic Resonance Imaging", "descriptor_ui": "D008279", "major_topic": false }, { "descriptor": "Neural Networks, Computer", "descriptor_ui": "D016571", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Dec", "date_precision": "unknown", "issue": "", "normalized_date": null, "pages": "102227", "proceedings_title": null, "publisher": "", "title": "Medical image analysis", "volume": "74", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Decomposing normal and abnormal features of medical images for content-based image retrieval of glioma imaging.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The bending of epithelial tubes is a fundamental process in organ morphogenesis, driven by various multicellular behaviours. The cochlea in the mammalian inner ear is a representative example of spiral tissue architecture where the continuous bending of the duct is a fundamental component of its morphogenetic process. Although the cochlear duct morphogenesis has been studied by genetic approaches extensively, it is still unclear how the cochlear duct morphology is physically formed. Here, we report that nuclear behaviour changes are associated with the curvature of the pseudostratified epithelium during murine cochlear development. Two-photon live-cell imaging reveals that the nuclei shuttle between the luminal and basal edges of the cell is in phase with cell-cycle progression, known as interkinetic nuclear migration, in the flat region of the pseudostratified epithelium. However, the nuclei become stationary on the luminal side following mitosis in the curved region. Mathematical modelling together with perturbation experiments shows that this nuclear stalling facilitates luminal-basal differential growth within the epithelium, suggesting that the nuclear stalling would contribute to the bending of the pseudostratified epithelium during the cochlear duct development. The findings suggest a possible scenario of differential growth which sculpts the tissue shape, driven by collective nuclear dynamics.", "classifications": [], "creators": [ { "creator_type": "author", "first_name": "Mamoru", "last_name": "Ishii", "name": null }, { "creator_type": "author", "first_name": "Tomoko", "last_name": "Tateya", "name": null }, { "creator_type": "author", "first_name": "Michiyuki", "last_name": "Matsuda", "name": null }, { "creator_type": "author", "first_name": "Tsuyoshi", "last_name": "Hirashima", "name": null } ], "identifiers": { "doi": { "normalized": "10.1098/rsos.211024" }, "pmcid": { "normalized": "PMC8652271" }, "pmid": { "normalized": "34909216" } }, "mesh": [], "publication": { "conference_name": null, "date": "2021 Dec", "date_precision": "unknown", "issue": "12", "normalized_date": null, "pages": "211024", "proceedings_title": null, "publisher": "", "title": "Royal Society open science", "volume": "8", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Stalling interkinetic nuclear migration in curved pseudostratified epithelium of developing cochlea.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Heterogeneous nuclear ribonucleoprotein L‐like (HNRNPLL), a suppressor of colorectal cancer (CRC) metastasis, is transcriptionally downregulated when CRC cells undergo epithelial‐mesenchymal transition (EMT). Here we show that decrease of MYB mediates the downregulation of HNRNPLL during EMT. The promoter activity was attributed to a region from −273 to −10 base pairs upstream of the transcription start site identified by 5'‐RACE analysis, and the region contained potential binding sites for MYB and SP1. Luciferase reporter gene assays and knockdown or knockout experiments for genes encoding the MYB family proteins, MYB, MYBL1, and MYBL2, revealed that MYB was responsible for approximately half of the promoter activity. On the other hand, treatment with mithramycin A, an inhibitor for SP1 and SP3, suppressed the promoter activity and their additive contribution was confirmed by knockout experiments. The expression level of MYB was reduced on EMT while that of SP1 and SP3 was unchanged, suggesting that the downregulation of HNRNPLL during EMT was mediated by the decrease of MYB expression while SP1 and SP3 determine the basal transcription level of HNRNPLL. Histopathological analysis confirmed the accumulation of MYB‐downregulated cancer cells at the invasion front of clinical CRC tissues. These results provide an insight into the molecular mechanism underlying CRC progression.", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Keiichiro", "last_name": "Sakuma", "name": null }, { "creator_type": "author", "first_name": "Eiichi", "last_name": "Sasaki", "name": null }, { "creator_type": "author", "first_name": "Waki", "last_name": "Hosoda", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Komori", "name": null }, { "creator_type": "author", "first_name": "Yasuhiro", "last_name": "Shimizu", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Aoki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/cas.15069" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "34286904" } }, "mesh": [ { "descriptor": "Binding Sites", "descriptor_ui": "D001665", "major_topic": false }, { "descriptor": "Cell Proliferation", "descriptor_ui": "D049109", "major_topic": false }, { "descriptor": "Colorectal Neoplasms", "descriptor_ui": "D015179", "major_topic": false }, { "descriptor": "Disease Progression", "descriptor_ui": "D018450", "major_topic": false }, { "descriptor": "Down-Regulation", "descriptor_ui": "D015536", "major_topic": false }, { "descriptor": "Epithelial-Mesenchymal Transition", "descriptor_ui": "D058750", "major_topic": false }, { "descriptor": "Gene Expression Regulation, Neoplastic", "descriptor_ui": "D015972", "major_topic": false }, { "descriptor": "Gene Knockdown Techniques", "descriptor_ui": "D055785", "major_topic": false }, { "descriptor": "Gene Knockout Techniques", "descriptor_ui": "D055786", "major_topic": false }, { "descriptor": "Heterogeneous-Nuclear Ribonucleoproteins", "descriptor_ui": "D034441", "major_topic": false }, { "descriptor": "HT29 Cells", "descriptor_ui": "D019073", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Neoplasm Metastasis", "descriptor_ui": "D009362", "major_topic": false }, { "descriptor": "Plicamycin", "descriptor_ui": "D008926", "major_topic": false }, { "descriptor": "Promoter Regions, Genetic", "descriptor_ui": "D011401", "major_topic": false }, { "descriptor": "Proto-Oncogene Proteins c-myb", "descriptor_ui": "D020598", "major_topic": false }, { "descriptor": "Sp1 Transcription Factor", "descriptor_ui": "D016329", "major_topic": false }, { "descriptor": "Transcription, Genetic", "descriptor_ui": "D014158", "major_topic": false }, { "descriptor": "Transfection", "descriptor_ui": "D014162", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Sep", "date_precision": "unknown", "issue": "9", "normalized_date": null, "pages": "3846-3855", "proceedings_title": null, "publisher": "", "title": "Cancer Science", "volume": "112", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "MYB mediates downregulation of the colorectal cancer metastasis suppressor heterogeneous nuclear ribonucleoprotein L‐like during epithelial‐mesenchymal transition.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Cancer stem-like cells (CSCs) induce drug resistance and recurrence of tumors when they experience DNA replication stress. However, the mechanisms underlying DNA replication stress in CSCs and its compensation remain unclear. Here, we demonstrate that upregulated c-Myc expression induces stronger DNA replication stress in patient-derived breast CSCs than in differentiated cancer cells. Our results suggest critical roles for mini-chromosome maintenance protein 10 (MCM10), a firing (activating) factor of DNA replication origins, to compensate for DNA replication stress in CSCs. MCM10 expression is upregulated in CSCs and is maintained by c-Myc. c-Myc-dependent collisions between RNA transcription and DNA replication machinery may occur in nuclei, thereby causing DNA replication stress. MCM10 may activate dormant replication origins close to these collisions to ensure the progression of replication. Moreover, patient-derived breast CSCs were found to be dependent on MCM10 for their maintenance, even after enrichment for CSCs that were resistant to paclitaxel, the standard chemotherapeutic agent. Further, MCM10 depletion decreased the growth of cancer cells, but not of normal cells. Therefore, MCM10 may robustly compensate for DNA replication stress and facilitate genome duplication in cancer cells in the S-phase, which is more pronounced in CSCs. Overall, we provide a preclinical rationale to target the c-Myc-MCM10 axis for preventing drug resistance and recurrence of tumors.", "classifications": [ { "id": "Okamoto", "label": "Group Okamoto", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Takahiko", "last_name": "Murayama", "name": null }, { "creator_type": "author", "first_name": "Yasuto", "last_name": "Takeuchi", "name": null }, { "creator_type": "author", "first_name": "Kaoru", "last_name": "Yamawaki", "name": null }, { "creator_type": "author", "first_name": "Toyoaki", "last_name": "Natsume", "name": null }, { "creator_type": "author", "first_name": "Mengjiao", "last_name": "Li", "name": null }, { "creator_type": "author", "first_name": "Rojas-Chaverra N.", "last_name": "Marcela", "name": null }, { "creator_type": "author", "first_name": "Tatsunori", "last_name": "Nishimura", "name": null }, { "creator_type": "author", "first_name": "Yuta", "last_name": "Kogure", "name": null }, { "creator_type": "author", "first_name": "Asuka", "last_name": "Nakata", "name": null }, { "creator_type": "author", "first_name": "Kana", "last_name": "Tominaga", "name": null }, { "creator_type": "author", "first_name": "Asako", "last_name": "Sasahara", "name": null }, { "creator_type": "author", "first_name": "Masao", "last_name": "Yano", "name": null }, { "creator_type": "author", "first_name": "Satoko", "last_name": "Ishikawa", "name": null }, { "creator_type": "author", "first_name": "Tetsuo", "last_name": "Ohta", "name": null }, { "creator_type": "author", "first_name": "Kazuhiro", "last_name": "Ikeda", "name": null }, { "creator_type": "author", "first_name": "Kuniko", "last_name": "Horie-Inoue", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Inoue", "name": null }, { "creator_type": "author", "first_name": "Masahide", "last_name": "Seki", "name": null }, { "creator_type": "author", "first_name": "Yutaka", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Sumio", "last_name": "Sugano", "name": null }, { "creator_type": "author", "first_name": "Takayuki", "last_name": "Enomoto", "name": null }, { "creator_type": "author", "first_name": "Masahiko", "last_name": "Tanabe", "name": null }, { "creator_type": "author", "first_name": "Kei-Ichiro", "last_name": "Tada", "name": null }, { "creator_type": "author", "first_name": "Masato T.", "last_name": "Kanemaki", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Okamoto", "name": null }, { "creator_type": "author", "first_name": "Arinobu", "last_name": "Tojo", "name": null }, { "creator_type": "author", "first_name": "Noriko", "last_name": "Gotoh", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/cas.14776" }, "pmcid": { "normalized": "PMC7935783" }, "pmid": { "normalized": "33340428" } }, "mesh": [ { "descriptor": "Antineoplastic Agents", "descriptor_ui": "D000970", "major_topic": false }, { "descriptor": "Breast", "descriptor_ui": "D001940", "major_topic": false }, { "descriptor": "Breast Neoplasms", "descriptor_ui": "D001943", "major_topic": false }, { "descriptor": "DNA Damage", "descriptor_ui": "D004249", "major_topic": false }, { "descriptor": "DNA Replication", "descriptor_ui": "D004261", "major_topic": false }, { "descriptor": "Drug Resistance, Neoplasm", "descriptor_ui": "D019008", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Minichromosome Maintenance Proteins", "descriptor_ui": "D064110", "major_topic": false }, { "descriptor": "Neoplasm Recurrence, Local", "descriptor_ui": "D009364", "major_topic": false }, { "descriptor": "Neoplastic Stem Cells", "descriptor_ui": "D014411", "major_topic": false }, { "descriptor": "Primary Cell Culture", "descriptor_ui": "D061251", "major_topic": false }, { "descriptor": "Proto-Oncogene Proteins c-myc", "descriptor_ui": "D016271", "major_topic": false }, { "descriptor": "Spheroids, Cellular", "descriptor_ui": "D018874", "major_topic": false }, { "descriptor": "Tumor Cells, Cultured", "descriptor_ui": "D014407", "major_topic": false }, { "descriptor": "Up-Regulation", "descriptor_ui": "D015854", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Mar", "date_precision": "unknown", "issue": "3", "normalized_date": null, "pages": "1209-1224", "proceedings_title": null, "publisher": "", "title": "Cancer science", "volume": "112", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "MCM10 compensates for Myc-induced DNA replication stress in breast cancer stem-like cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "INTRODUCTION: The WHO classification of lung tumors defines adenocarcinoma in situ (AIS) and minimally invasive adenocarcinoma (MIA) as cancers with no or limited histologic invasive components. The probability of patients with AIS or MIA being recurrence free for 5 years postoperatively has been found to be 100%. This study aimed to analyze the prognosis of patients with AIS or MIA after more than 5 postoperative years. METHODS: We reviewed the pathologic findings of 4768 patients who underwent resection for lung cancer between 1998 and 2010. Of these, 524 patients with curative resection for AIS (207 cases, 39.5%) and MIA (317 cases, 60.5%) were included. Postoperative recurrence, survival, and development of secondary primary lung cancer (SPLC) were analyzed. RESULTS: Of the included patients, 342 (65.3%) were of female sex, 333 (63.5%) were nonsmokers, and 229 (43.7%) underwent sublobar resection. Average pathologic total tumor diameter was 15.2 plus or minus 5.5 mm. Median postoperative follow-up period was 100 months (range: 1-237). No recurrence of lung cancer was observed for either AIS or MIA cases. Estimated 10-year postoperative disease-specific survival rates were 100% and 100% (p = 0.72), and overall survival rates were 95.3% and 97.8% (p = 0.94) for AIS and MIA cases, respectively. Estimated incidence rates of metachronous SPLC at 10 years after surgery were 5.6% and 7.7% for AIS and MIA, respectively (p = 0.45), and these were not correlated with the EGFR mutation status. CONCLUSIONS: Although the development of metachronous SPLC should be noted, the risk of recurrence is quite low at more than 5 years after resection of AIS and MIA. This finding strengthens the clinical value of distinguishing AIS and MIA from other adenocarcinomas of the lung.", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Masaya", "last_name": "Yotsukura", "name": null }, { "creator_type": "author", "first_name": "Hisao", "last_name": "Asamura", "name": null }, { "creator_type": "author", "first_name": "Noriko", "last_name": "Motoi", "name": null }, { "creator_type": "author", "first_name": "Jumpei", "last_name": "Kashima", "name": null }, { "creator_type": "author", "first_name": "Yukihiro", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Kazuo", "last_name": "Nakagawa", "name": null }, { "creator_type": "author", "first_name": "Kouya", "last_name": "Shiraishi", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Kohno", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null }, { "creator_type": "author", "first_name": "Shun-Ichi", "last_name": "Watanabe", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.jtho.2021.04.007" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "33915249" } }, "mesh": [ { "descriptor": "Adenocarcinoma", "descriptor_ui": "D000230", "major_topic": true }, { "descriptor": "Adenocarcinoma in Situ", "descriptor_ui": "D065311", "major_topic": true }, { "descriptor": "Adenocarcinoma of Lung", "descriptor_ui": "D000077192", "major_topic": true }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Lung", "descriptor_ui": "D008168", "major_topic": false }, { "descriptor": "Lung Neoplasms", "descriptor_ui": "D008175", "major_topic": true }, { "descriptor": "Neoplasm Invasiveness", "descriptor_ui": "D009361", "major_topic": false }, { "descriptor": "Neoplasm Recurrence, Local", "descriptor_ui": "D009364", "major_topic": false }, { "descriptor": "Prognosis", "descriptor_ui": "D011379", "major_topic": false }, { "descriptor": "Retrospective Studies", "descriptor_ui": "D012189", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Aug", "date_precision": "unknown", "issue": "8", "normalized_date": null, "pages": "1312-1320", "proceedings_title": null, "publisher": "", "title": "Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer", "volume": "16", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Long-Term Prognosis of Patients With Resected Adenocarcinoma In Situ and Minimally Invasive Adenocarcinoma of the Lung.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "In vertebrates, retinal rod and cone photoreceptor cells rely significantly on glycolysis. Lactate released from photoreceptor cells fuels neighboring retinal pigment epithelium cells and Muller glial cells through oxidative phosphorylation. To understand this highly heterogeneous metabolic environment around photoreceptor cells, single-cell analysis is needed. Here, we visualized cellular AMP-activated protein kinase (AMPK) activity and ATP levels in the retina by two-photon microscopy. Transgenic mice expressing a hyBRET-AMPK biosensor were used for measuring the AMPK activity. GO-ATeam2 transgenic mice were used for measuring the ATP level. Temporal metabolic responses were successfully detected in the live retinal explants upon drug perfusion. A glycolysis inhibitor, 2-deoxy-d-glucose (2-DG), activated AMPK and reduced ATP. These effects were clearly stronger in rods than in cones. Notably, rod AMPK and ATP started to recover at 30 min from the onset of 2-DG perfusion. Consistent with these findings, ex vivo electroretinogram recordings showed a transient slowdown in rod dim flash responses during a 60-min 2-DG perfusion, whereas cone responses were not affected. Based on these results, we propose that cones surrounded by highly glycolytic rods become less dependent on glycolysis, and rods also become less dependent on glycolysis within 60 min upon the glycolysis inhibition.", "classifications": [], "creators": [ { "creator_type": "author", "first_name": "Jiazhou", "last_name": "He", "name": null }, { "creator_type": "author", "first_name": "Masamichi", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Kenta", "last_name": "Sumiyama", "name": null }, { "creator_type": "author", "first_name": "Yumi", "last_name": "Konagaya", "name": null }, { "creator_type": "author", "first_name": "Kenta", "last_name": "Terai", "name": null }, { "creator_type": "author", "first_name": "Michiyuki", "last_name": "Matsuda", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Sato", "name": null } ], "identifiers": { "doi": { "normalized": "10.1096/fj.202101121r" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "34449091" } }, "mesh": [ { "descriptor": "Adenosine Triphosphate", "descriptor_ui": "D000255", "major_topic": false }, { "descriptor": "AMP-Activated Protein Kinases", "descriptor_ui": "D055372", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Ependymoglial Cells", "descriptor_ui": "D063928", "major_topic": false }, { "descriptor": "Glycolysis", "descriptor_ui": "D006019", "major_topic": false }, { "descriptor": "Light", "descriptor_ui": "D008027", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Oxidative Phosphorylation", "descriptor_ui": "D010085", "major_topic": false }, { "descriptor": "Photons", "descriptor_ui": "D017785", "major_topic": false }, { "descriptor": "Retina", "descriptor_ui": "D012160", "major_topic": false }, { "descriptor": "Retinal Cone Photoreceptor Cells", "descriptor_ui": "D017949", "major_topic": false }, { "descriptor": "Retinal Rod Photoreceptor Cells", "descriptor_ui": "D017948", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Sep", "date_precision": "unknown", "issue": "9", "normalized_date": null, "pages": "e21880", "proceedings_title": null, "publisher": "", "title": "FASEB journal : official publication of the Federation of American Societies for Experimental Biology", "volume": "35", "year": 2021 }, "ssbd": { "database": [], "repository": [ "ssbd-repos-000175" ] }, "title": "Two-photon AMPK and ATP imaging reveals the bias between rods and cones in glycolysis utility.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Histone acetyltransferases (HATs) catalyze the transfer of an acetyl group from acetyl-CoA to lysine residues of histones and play a central role in transcriptional regulation in diverse biological processes. Dysregulation of HAT activity can lead to human diseases including developmental disorders and cancer. Through genome-wide CRISPR-Cas9 screens, we identified several HATs of the MYST family as fitness genes for acute myeloid leukemia (AML). Here we investigate the essentiality of lysine acetyltransferase KAT7 in AMLs driven by the MLL-X gene fusions. We found that KAT7 loss leads to a rapid and complete loss of both H3K14ac and H4K12ac marks, in association with reduced proliferation, increased apoptosis, and differentiation of AML cells. Acetyltransferase activity of KAT7 is essential for the proliferation of these cells. Mechanistically, our data propose that acetylated histones provide a platform for the recruitment of MLL-fusion-associated adaptor proteins such as BRD4 and AF4 to gene promoters. Upon KAT7 loss, these factors together with RNA polymerase II rapidly dissociate from several MLL-fusion target genes that are essential for AML cell proliferation, including MEIS1, PBX3, and SENP6. Our findings reveal that KAT7 is a plausible therapeutic target for this poor prognosis AML subtype.", "classifications": [ { "id": "Yusa", "label": "Group Yusa", "parent": "Eiraku", "type": "group" }, { "id": "Eiraku", "label": "Team Eiraku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yan Zi", "last_name": "Au", "name": null }, { "creator_type": "author", "first_name": "Muxin", "last_name": "Gu", "name": null }, { "creator_type": "author", "first_name": "Etienne", "last_name": "De Braekeleer", "name": null }, { "creator_type": "author", "first_name": "Malgorzata", "last_name": "Gozdecka", "name": null }, { "creator_type": "author", "first_name": "Demetrios", "last_name": "Aspris", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Tarumoto", "name": null }, { "creator_type": "author", "first_name": "Jonathan", "last_name": "Cooper", "name": null }, { "creator_type": "author", "first_name": "Jason", "last_name": "Yu", "name": null }, { "creator_type": "author", "first_name": "Swee Hoe", "last_name": "Ong", "name": null }, { "creator_type": "author", "first_name": "Xi", "last_name": "Chen", "name": null }, { "creator_type": "author", "first_name": "Konstantinos", "last_name": "Tzelepis", "name": null }, { "creator_type": "author", "first_name": "Brian J. P.", "last_name": "Huntly", "name": null }, { "creator_type": "author", "first_name": "George", "last_name": "Vassiliou", "name": null }, { "creator_type": "author", "first_name": "Kosuke", "last_name": "Yusa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41375-020-1001-z" }, "pmcid": { "normalized": "PMC7610570" }, "pmid": { "normalized": "32764680" } }, "mesh": [ { "descriptor": "Apoptosis", "descriptor_ui": "D017209", "major_topic": false }, { "descriptor": "Biomarkers, Tumor", "descriptor_ui": "D014408", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Disease Management", "descriptor_ui": "D019468", "major_topic": false }, { "descriptor": "Epigenesis, Genetic", "descriptor_ui": "D044127", "major_topic": false }, { "descriptor": "Gene Knockout Techniques", "descriptor_ui": "D055786", "major_topic": false }, { "descriptor": "Gene Rearrangement", "descriptor_ui": "D015321", "major_topic": true }, { "descriptor": "Genetic Association Studies", "descriptor_ui": "D056726", "major_topic": false }, { "descriptor": "Genetic Predisposition to Disease", "descriptor_ui": "D020022", "major_topic": true }, { "descriptor": "Histone Acetyltransferases", "descriptor_ui": "D051548", "major_topic": false }, { "descriptor": "Histone-Lysine N-Methyltransferase", "descriptor_ui": "D011495", "major_topic": false }, { "descriptor": "Histones", "descriptor_ui": "D006657", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Leukemia, Myeloid, Acute", "descriptor_ui": "D015470", "major_topic": false }, { "descriptor": "Myeloid Cells", "descriptor_ui": "D022423", "major_topic": false }, { "descriptor": "Myeloid-Lymphoid Leukemia Protein", "descriptor_ui": "D051788", "major_topic": false }, { "descriptor": "Oncogene Proteins, Fusion", "descriptor_ui": "D015514", "major_topic": false }, { "descriptor": "Promoter Regions, Genetic", "descriptor_ui": "D011401", "major_topic": false }, { "descriptor": "Protein Binding", "descriptor_ui": "D011485", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Apr", "date_precision": "unknown", "issue": "4", "normalized_date": null, "pages": "1012-1022", "proceedings_title": null, "publisher": "", "title": "Leukemia", "volume": "35", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "KAT7 is a genetic vulnerability of acute myeloid leukemias driven by MLL rearrangements.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND/AIM: Circulating tumor cells (CTCs) is one of the promising markers that predict dissemination and metastases. This study aimed to identify the relationship between CTCs in pulmonary vein (PuV) and spread through air space (STAS) in non-small cell lung cancers. MATERIALS AND METHODS: We applied a cytology-based microfluidic platform for rare cell isolation. Twenty-four patients were enrolled. RESULTS: The rate of CTC detection in PuV was 79.2%, and STAS was observed in 54.2% of the samples. When the definitive cut-off value was 1 CTC/1 ml, of the 14 CTC-PuV-high cases, 11 (78.6%) were STAS-positive, whereas 2 of the 10 (20.0%) CTC-PuV-low cases were STAS-positive, and the difference between the two groups was statistically significant (p=0.02). CTC-PuV-high exhibited a significantly poorer survival (p<0.01). CONCLUSION: The higher frequency of STAS is significantly associated with a higher number of CTCs in PuV, and the combination of STAS and CTC was significantly associated with poor prognosis.", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Hiroaki", "last_name": "Kuroda", "name": null }, { "creator_type": "author", "first_name": "Katsuhiro", "last_name": "Masago", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Shiro", "last_name": "Fujita", "name": null }, { "creator_type": "author", "first_name": "Eiichi", "last_name": "Sasaki", "name": null }, { "creator_type": "author", "first_name": "Takeo", "last_name": "Nakada", "name": null }, { "creator_type": "author", "first_name": "Noriaki", "last_name": "Sakakura", "name": null }, { "creator_type": "author", "first_name": "Hayao", "last_name": "Nakanishi", "name": null }, { "creator_type": "author", "first_name": "Hirokazu", "last_name": "Matsushita", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null } ], "identifiers": { "doi": { "normalized": "10.21873/anticanres.15363" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "34732420" } }, "mesh": [ { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Carcinoma, Non-Small-Cell Lung", "descriptor_ui": "D002289", "major_topic": false }, { "descriptor": "Cell Movement", "descriptor_ui": "D002465", "major_topic": true }, { "descriptor": "Cell Separation", "descriptor_ui": "D002469", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Lung Neoplasms", "descriptor_ui": "D008175", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Microfluidic Analytical Techniques", "descriptor_ui": "D046210", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Neoplasm Invasiveness", "descriptor_ui": "D009361", "major_topic": false }, { "descriptor": "Neoplasm Staging", "descriptor_ui": "D009367", "major_topic": false }, { "descriptor": "Neoplastic Cells, Circulating", "descriptor_ui": "D009360", "major_topic": false }, { "descriptor": "Pneumonectomy", "descriptor_ui": "D011013", "major_topic": false }, { "descriptor": "Prospective Studies", "descriptor_ui": "D011446", "major_topic": false }, { "descriptor": "Pulmonary Veins", "descriptor_ui": "D011667", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Nov", "date_precision": "unknown", "issue": "11", "normalized_date": null, "pages": "5499-5505", "proceedings_title": null, "publisher": "", "title": "Anticancer research", "volume": "41", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Positive Correlation Between the Number of Circulating Tumor Cells in the Pulmonary Vein and Tumor Spread Through Air Spaces in Resected Non-small Cell Lung Cancer.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "cAMP responsive element-binding protein H (CREBH) is a hepatic transcription factor to be activated during fasting. We generated CREBH knock-in flox mice, and then generated liver-specific CREBH transgenic (CREBH L-Tg) mice in an active form. CREBH L-Tg mice showed a delay in growth in the postnatal stage. Plasma growth hormone (GH) levels were significantly increased in CREBH L-Tg mice, but plasma insulin-like growth factor 1 (IGF1) levels were significantly decreased, indicating GH resistance. In addition, CREBH overexpression significantly increased hepatic mRNA and plasma levels of FGF21, which is thought to be as one of the causes of growth delay. However, the additional ablation of FGF21 in CREBH L-Tg mice could not correct GH resistance at all. CREBH L-Tg mice sustained GH receptor (GHR) reduction and the increase of IGF binding protein 1 (IGFBP1) in the liver regardless of FGF21. As GHR is a first step in GH signaling, the reduction of GHR leads to impairment of GH signaling. These data suggest that CREBH negatively regulates growth in the postnatal growth stage via various pathways as an abundant energy response by antagonizing GH signaling.", "classifications": [ { "id": "Miyamoto", "label": "Group Miyamoto", "parent": "Wakamoto", "type": "group" }, { "id": "Wakamoto", "label": "Team Wakamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yoshimi", "last_name": "Nakagawa", "name": null }, { "creator_type": "author", "first_name": "Kae", "last_name": "Kumagai", "name": null }, { "creator_type": "author", "first_name": "Song-Iee", "last_name": "Han", "name": null }, { "creator_type": "author", "first_name": "Yuhei", "last_name": "Mizunoe", "name": null }, { "creator_type": "author", "first_name": "Masaya", "last_name": "Araki", "name": null }, { "creator_type": "author", "first_name": "Seiya", "last_name": "Mizuno", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Ohno", "name": null }, { "creator_type": "author", "first_name": "Kazuya", "last_name": "Matsuo", "name": null }, { "creator_type": "author", "first_name": "Yasunari", "last_name": "Yamada", "name": null }, { "creator_type": "author", "first_name": "Jun-Dal", "last_name": "Kim", "name": null }, { "creator_type": "author", "first_name": "Takafumi", "last_name": "Miyamoto", "name": null }, { "creator_type": "author", "first_name": "Motohiro", "last_name": "Sekiya", "name": null }, { "creator_type": "author", "first_name": "Morichika", "last_name": "Konishi", "name": null }, { "creator_type": "author", "first_name": "Nobuyuki", "last_name": "Itoh", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Matsuzaka", "name": null }, { "creator_type": "author", "first_name": "Satoru", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Hirohito", "last_name": "Sone", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Shimano", "name": null } ], "identifiers": { "doi": { "normalized": "10.1096/fj.202002784rr" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "34042217" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Body Composition", "descriptor_ui": "D001823", "major_topic": true }, { "descriptor": "Body Mass Index", "descriptor_ui": "D015992", "major_topic": true }, { "descriptor": "Cyclic AMP Response Element-Binding Protein", "descriptor_ui": "D017362", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Fibroblast Growth Factors", "descriptor_ui": "D005346", "major_topic": false }, { "descriptor": "Gene Expression Regulation, Developmental", "descriptor_ui": "D018507", "major_topic": true }, { "descriptor": "Growth Hormone", "descriptor_ui": "D013006", "major_topic": false }, { "descriptor": "Liver", "descriptor_ui": "D008099", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Mice, Transgenic", "descriptor_ui": "D008822", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Jun", "date_precision": "unknown", "issue": "6", "normalized_date": null, "pages": "e21663", "proceedings_title": null, "publisher": "", "title": "FASEB journal : official publication of the Federation of American Societies for Experimental Biology", "volume": "35", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Starvation-induced transcription factor CREBH negatively governs body growth by controlling GH signaling.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "OBJECTIVES: This study aims to evaluate whether the accumulation of TP53 mutations is associated with clinical outcome by comparing full-coverage TP53 deep sequencing of the initial and recurrent head and neck squamous cell carcinoma (HNSCC). MATERIALS AND METHODS: Medical records and surgical specimens of 400 patients with HNSCC surgically treated with curative intent, of which 95 patients developed local or locoregional recurrence, were reviewed. Of these patients, 63 were eligible for genomic analysis. Full-coverage TP53 deep sequencing of 126 paired initial and recurrent tumor samples was examined using next-generation sequencing (NGS). Temporal changes in the mutation status, molecular characterization, and clinical outcome were compared. Fisher's exact test, Kaplan-Meier method, log-rank test, and Cox regression models were used for statistical analysis. RESULTS: Of the recurrent tumors, 22% harbored accumulation of TP53 mutations, and 16% lost the original mutation. The accumulation of TP53 mutations was significantly more frequent in oral cancer than in pharyngeal or laryngeal cancer (33% vs. 7%, p = 0.016). Two-year post-recurrence survival (PRS) was associated with TP53 status for recurrent tumors, but not for initial tumors. The TP53 status for recurrent tumors was an independent risk factor in multivariate analysis (hazard ratio, 5.76; 95% confidence interval, 1.86-17.8; p = 0.0023). CONCLUSION: Approximately one-third of the recurrent HNSCC cases showed a different TP53 status from the initial tumor. Temporal changes in the mutation status differed by primary site. Full-coverage TP53 deep sequencing of recurrent tumors was useful in predicting post-recurrence prognosis.", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Kenya", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Seiichi", "last_name": "Yoshimoto", "name": null }, { "creator_type": "author", "first_name": "Mizuo", "last_name": "Ando", "name": null }, { "creator_type": "author", "first_name": "Fumihiko", "last_name": "Matsumoto", "name": null }, { "creator_type": "author", "first_name": "Naoya", "last_name": "Murakami", "name": null }, { "creator_type": "author", "first_name": "Go", "last_name": "Omura", "name": null }, { "creator_type": "author", "first_name": "Yoshitaka", "last_name": "Honma", "name": null }, { "creator_type": "author", "first_name": "Yoshifumi", "last_name": "Matsumoto", "name": null }, { "creator_type": "author", "first_name": "Atsuo", "last_name": "Ikeda", "name": null }, { "creator_type": "author", "first_name": "Azusa", "last_name": "Sakai", "name": null }, { "creator_type": "author", "first_name": "Kohtaro", "last_name": "Eguchi", "name": null }, { "creator_type": "author", "first_name": "Akiko", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Eigitsu", "last_name": "Ryo", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null }, { "creator_type": "author", "first_name": "Taisuke", "last_name": "Mori", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.oraloncology.2020.105091" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "33249291" } }, "mesh": [ { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Neoplasm Recurrence, Local", "descriptor_ui": "D009364", "major_topic": false }, { "descriptor": "Prognosis", "descriptor_ui": "D011379", "major_topic": false }, { "descriptor": "Squamous Cell Carcinoma of Head and Neck", "descriptor_ui": "D000077195", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Feb", "date_precision": "unknown", "issue": "", "normalized_date": null, "pages": "105091", "proceedings_title": null, "publisher": "", "title": "Oral oncology", "volume": "113", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Full-coverage TP53 deep sequencing of recurrent head and neck squamous cell carcinoma facilitates prognostic assessment after recurrence.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Mutations of the gene encoding the RET tyrosine kinase causes Hirschsprung's disease (HSCR) and medullary thyroid carcinoma (MTC). Current consensus holds that HSCR and MTC are induced by inactivating and activating RET mutations, respectively. However, it remains unknown whether activating mutations in the RET gene have adverse effects on ENS development in vivo We addressed this issue by examining mice engineered to express RET51(C618F), an activating mutation identified in MTC patients. Although Ret(51(C618F)/51(C618F)) mice displayed hyperganglionosis of the ENS, Ret(51(C618F)/-) mice exhibited severe intestinal aganglionosis because of premature neuronal differentiation. Reduced levels of glial cell-derived neurotrophic factor (GDNF), a RET-activating neurotrophic factor, ameliorated the ENS phenotype of Ret(51(C618F)/-) mice, demonstrating that GDNF-mediated activation of RET51(C618F) is responsible for severe aganglionic phenotype. The RET51(C618F) allele showed genetic interaction with Ednrb gene, one of modifier genes for HSCR. These data reveal that proliferation and differentiation of ENS precursors are exquisitely controlled by both the activation levels and total dose of RET. Increased RET activity coupled with a decreased gene dosage can cause intestinal aganglionosis, a finding that provides novel insight into HSCR pathogenesis.", "classifications": [ { "id": "Enomoto", "label": "Group Enomoto", "parent": "Enomoto", "type": "group" }, { "id": "Enomoto", "label": "Team Enomoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Mitsumasa", "last_name": "Okamoto", "name": null }, { "creator_type": "author", "first_name": "Toshihiro", "last_name": "Uesaka", "name": null }, { "creator_type": "author", "first_name": "Keisuke", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Hideki", "last_name": "Enomoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1523/eneuro.0534-20.2021" }, "pmcid": { "normalized": "PMC8174796" }, "pmid": { "normalized": "33958373" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Gene Dosage", "descriptor_ui": "D018628", "major_topic": false }, { "descriptor": "Glial Cell Line-Derived Neurotrophic Factor", "descriptor_ui": "D051100", "major_topic": false }, { "descriptor": "Hirschsprung Disease", "descriptor_ui": "D006627", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": false }, { "descriptor": "Proto-Oncogene Proteins c-ret", "descriptor_ui": "D051096", "major_topic": true } ], "publication": { "conference_name": null, "date": "2021 May-Jun", "date_precision": "unknown", "issue": "3", "normalized_date": null, "pages": "ENEURO.0534-20.2021", "proceedings_title": null, "publisher": "", "title": "eNeuro", "volume": "8", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Increased RET Activity Coupled with a Reduction in the RET Gene Dosage Causes Intestinal Aganglionosis in Mice.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Peritoneal metastasis, a hallmark of incurable advanced gastric cancer (GC), presently has no curative therapy and its molecular features have not been examined extensively. Here we present a comprehensive multi-omic analysis of malignant ascitic fluid samples and their corresponding tumor cell lines from 98 patients, including whole-genome sequencing, RNA sequencing, DNA methylation and enhancer landscape. We identify a higher frequency of receptor tyrosine kinase and mitogen-activated protein kinase pathway alterations compared to primary GC; moreover, approximately half of the gene alterations are potentially treatable with targeted therapy. Our analyses also stratify ascites-disseminated GC into two distinct molecular subtypes: one displaying active super enhancers (SEs) at the ELF3, KLF5 and EHF loci, and a second subtype bearing transforming growth factor-beta (TGF-beta) pathway activation through SMAD3 SE activation and high expression of transcriptional enhancer factor TEF-1 (TEAD1). In the TGF-beta subtype, inhibition of the TEAD pathway circumvents therapy resistance, suggesting a potential molecular-guided therapeutic strategy for this subtype of intractable GC.", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yosuke", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Fumiko", "last_name": "Chiwaki", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Kojima", "name": null }, { "creator_type": "author", "first_name": "Masahito", "last_name": "Kawazu", "name": null }, { "creator_type": "author", "first_name": "Masayuki", "last_name": "Komatsu", "name": null }, { "creator_type": "author", "first_name": "Toshihide", "last_name": "Ueno", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Inoue", "name": null }, { "creator_type": "author", "first_name": "Shigeki", "last_name": "Sekine", "name": null }, { "creator_type": "author", "first_name": "Keisuke", "last_name": "Matsusaki", "name": null }, { "creator_type": "author", "first_name": "Hiromichi", "last_name": "Matsushita", "name": null }, { "creator_type": "author", "first_name": "Narikazu", "last_name": "Boku", "name": null }, { "creator_type": "author", "first_name": "Yae", "last_name": "Kanai", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null }, { "creator_type": "author", "first_name": "Hiroki", "last_name": "Sasaki", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Mano", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s43018-021-00240-6" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "35121863" } }, "mesh": [ { "descriptor": "Ascites", "descriptor_ui": "D001201", "major_topic": false }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Peritoneal Neoplasms", "descriptor_ui": "D010534", "major_topic": true }, { "descriptor": "Stomach Neoplasms", "descriptor_ui": "D013274", "major_topic": true }, { "descriptor": "Transforming Growth Factor beta", "descriptor_ui": "D016212", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Sep", "date_precision": "unknown", "issue": "9", "normalized_date": null, "pages": "962-977", "proceedings_title": null, "publisher": "", "title": "Nature cancer", "volume": "2", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Multi-omic profiling of peritoneal metastases in gastric cancer identifies molecular subtypes and therapeutic vulnerabilities.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "INTRODUCTION: We describe our ongoing multicenter, prospective, single-arm, phase II trial of neoadjuvant concurrent chemo-immuno-radiation therapy followed by surgical resection and adjuvant immunotherapy for resectable stage IIIA-B (discrete N2) non-small-cell lung cancer (NSCLC) (registered at the Japan Pharmaceutical Information Center, Clinical Trials Information-195069). PATIENTS AND METHODS: Key inclusion criteria include (1) clinical T1-3/T4 (tumor size) N2 stage IIIA-B NSCLC, and (2) pathologically confirmed N2 without extranodal invasion (based on diagnostic imaging). Patients will receive concurrent chemoradiotherapy (carboplatin [area under the curve = 2] and paclitaxel [40 mg/m(2)] on days 1, 8, 15, 22, and 29, with involved-field radiation therapy [RT] [dose 50 Gy] on days 1-25) and neoadjuvant immunotherapy (durvalumab [1500 mg] on days 1 and 29). Surgical resection with mediastinal lymph node dissection is performed within 2 to 6 weeks after RT. Consolidation therapy with durvalumab is administered for up to 1 year after surgery. The primary endpoint is major pathologic response (MPR) (1) are cysteine derivatives having sulfane sulfur atoms bound to cysteine thiol. Recent advances in the development of analytical methods for detection and quantification of persulfides and polysulfides have revealed the biological presence, in both prokaryotes and eukaryotes, of persulfide/polysulfide in diverse forms such as CysSSH, glutathione persulfide and protein persulfides. Accumulating evidence has suggested that persulfide/polysulfide species may involve in a variety of biological events such as biosyntheses of sulfur-containing molecules, tRNA modification, regulation of redox-dependent signal transduction, mitochondrial energy metabolism via sulfur respiration, cytoprotection from oxidative stress via their antioxidant activities, and anti-inflammation against Toll-like receptor-mediated inflammatory responses. Development of chemical sulfur donors may facilitate further understanding of physiological and pathophysiological roles of persulfide/polysulfide species, including regulatory roles of these species in immune responses.", "classifications": [ { "id": "Akaike", "label": "Group Akaike", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Tianli", "last_name": "Zhang", "name": null }, { "creator_type": "author", "first_name": "Hiroyasu", "last_name": "Tsutsuki", "name": null }, { "creator_type": "author", "first_name": "Katushiko", "last_name": "Ono", "name": null }, { "creator_type": "author", "first_name": "Takaaki", "last_name": "Akaike", "name": null }, { "creator_type": "author", "first_name": "Tomohiro", "last_name": "Sawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.3164/jcbn.20-13" }, "pmcid": { "normalized": "PMC7844669" }, "pmid": { "normalized": "33536706" } }, "mesh": [], "publication": { "conference_name": null, "date": "2021 Jan", "date_precision": "unknown", "issue": "1", "normalized_date": null, "pages": "5-8", "proceedings_title": null, "publisher": "", "title": "Journal of clinical biochemistry and nutrition", "volume": "68", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Antioxidative and anti-inflammatory actions of reactive cysteine persulfides.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Comprehensive genomic profiling (CGP) is being increasingly used for the routine clinical management of solid cancers. In July 2018, the use of tumor tissue‐based CGP assays became available for all solid cancers under the universal health insurance system in Japan. Several restrictions presently exist, such as patient eligibility and limitations on the opportunities to perform such assays. The clinical implementation of CGP based on plasma circulating tumor DNA (ctDNA) is also expected to raise issues regarding the selection and use of tissue DNA and ctDNA CGP. A Joint Task Force for the Promotion of Cancer Genome Medicine comprised of three Japanese cancer‐related societies has formulated a policy proposal for the appropriate use of plasma CGP (in Japanese), available at https://www.jca.gr.jp/researcher/topics/2021/files/20210120.pdf, http://www.jsco.or.jp/jpn/user_data/upload/File/20210120.pdf, and https://www.jsmo.or.jp/file/dl/newsj/2765.pdf. Based on these recommendations, the working group has summarized the respective advantages and cautions regarding the use of tissue DNA CGP and ctDNA CGP with reference to the advice of a multidisciplinary expert panel, the preferred use of plasma specimens over tissue, and multiple ctDNA testing. These recommendations have been prepared to maximize the benefits of performing CGP assays and might be applicable in other countries and regions.", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Kuniko", "last_name": "Sunami", "name": null }, { "creator_type": "author", "first_name": "Hideaki", "last_name": "Bando", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null }, { "creator_type": "author", "first_name": "Yoichi", "last_name": "Naito", "name": null }, { "creator_type": "author", "first_name": "Hideaki", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Katsuya", "last_name": "Tsuchihara", "name": null }, { "creator_type": "author", "first_name": "Shinichi", "last_name": "Toyooka", "name": null }, { "creator_type": "author", "first_name": "Koshi", "last_name": "Mimori", "name": null }, { "creator_type": "author", "first_name": "Shinji", "last_name": "Kohsaka", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Uetake", "name": null }, { "creator_type": "author", "first_name": "Ichiro", "last_name": "Kinoshita", "name": null }, { "creator_type": "author", "first_name": "Keigo", "last_name": "Komine", "name": null }, { "creator_type": "author", "first_name": "Masayuki", "last_name": "Takeda", "name": null }, { "creator_type": "author", "first_name": "Tetsu", "last_name": "Hayashida", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Tamura", "name": null }, { "creator_type": "author", "first_name": "Kazuto", "last_name": "Nishio", "name": null }, { "creator_type": "author", "first_name": "Noboru", "last_name": "Yamamoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/cas.15022" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "34128569" } }, "mesh": [ { "descriptor": "Biomarkers, Tumor", "descriptor_ui": "D014408", "major_topic": false }, { "descriptor": "Blood Specimen Collection", "descriptor_ui": "D001800", "major_topic": false }, { "descriptor": "Circulating Tumor DNA", "descriptor_ui": "D000074141", "major_topic": false }, { "descriptor": "Gene Expression Profiling", "descriptor_ui": "D020869", "major_topic": false }, { "descriptor": "Guidelines as Topic", "descriptor_ui": "D017408", "major_topic": true }, { "descriptor": "High-Throughput Nucleotide Sequencing", "descriptor_ui": "D059014", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Japan", "descriptor_ui": "D007564", "major_topic": false }, { "descriptor": "Liquid Biopsy", "descriptor_ui": "D000073890", "major_topic": false }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": false }, { "descriptor": "Neoplasms", "descriptor_ui": "D009369", "major_topic": false }, { "descriptor": "Transcriptome", "descriptor_ui": "D059467", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Sep", "date_precision": "unknown", "issue": "9", "normalized_date": null, "pages": "3911-3917", "proceedings_title": null, "publisher": "", "title": "Cancer Science", "volume": "112", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Appropriate use of cancer comprehensive genome profiling assay using circulating tumor DNA.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "A 79-year-old man presented with high fever, marked eosinophilia, altered biochemical liver function tests (LFT) with predominance of biliary enzymes, and severe wall thickening of the gallbladder. Magnetic resonance cholangiopancreatography (MRCP) suggested cholecystitis, without signs of biliary strictures. Laparoscopic cholecystectomy and exploratory liver excision revealed eosinophilic cholangitis and cholecystitis, complicated with hepatitis and portal phlebitis. Prednisolone monotherapy rapidly improved peripheral eosinophilia, but not LFT. Liver biopsy showed that infiltrating eosinophils were replaced by lymphocytes and plasma cells. Treatment with ursodeoxycholic acid improved LFT abnormalities. Nevertheless, after 2 months, transaminase-dominant LFT abnormalities appeared. Transient prednisolone dose increase improved LFT, but biliary enzymes' levels re-elevated and jaundice progressed. The second and third MRCP within a 7-month interval showed rapid progression of biliary stricture. The repeated liver biopsy showed lymphocytic, not eosinophilic, peribiliary infiltration and hepatocellular reaction to cholestasis. Eighteen months after the first visit, the patient died of hepatic failure. Autopsy specimen of the liver showed lymphocyte-dominant peribiliary infiltration and bridging fibrosis due to cholestasis. Though eosinophil-induced biliary damage was an initial trigger, repeated biopsy suggested that lymphocytes played a key role in progression of the disease. Further studies are needed to elucidate the relationship between eosinophils and lymphocytes in eosinophilic cholangitis.", "classifications": [ { "id": "Tanaka", "label": "Group Tanaka", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Takahito", "last_name": "Shimomura", "name": null }, { "creator_type": "author", "first_name": "Tomoki", "last_name": "Nakajima", "name": null }, { "creator_type": "author", "first_name": "Toshiaki", "last_name": "Nakashima", "name": null }, { "creator_type": "author", "first_name": "Yasutaka", "last_name": "Morimoto", "name": null }, { "creator_type": "author", "first_name": "Junko", "last_name": "Yamaoka", "name": null }, { "creator_type": "author", "first_name": "Akiko", "last_name": "Shibuya", "name": null }, { "creator_type": "author", "first_name": "Tomoyuki", "last_name": "Ohno", "name": null }, { "creator_type": "author", "first_name": "Norimasa", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Mitsuo", "last_name": "Kishimoto", "name": null }, { "creator_type": "author", "first_name": "Eiichi", "last_name": "Konishi", "name": null }, { "creator_type": "author", "first_name": "Hideo", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Michihisa", "last_name": "Moriguchi", "name": null }, { "creator_type": "author", "first_name": "Yoshito", "last_name": "Itoh", "name": null } ], "identifiers": { "doi": { "normalized": "10.1159/000512420" }, "pmcid": { "normalized": "PMC7989825" }, "pmid": { "normalized": "33790710" } }, "mesh": [], "publication": { "conference_name": null, "date": "2021 Jan-Apr", "date_precision": "unknown", "issue": "1", "normalized_date": null, "pages": "232-243", "proceedings_title": null, "publisher": "", "title": "Case reports in gastroenterology", "volume": "15", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Eosinophilic Cholangitis with Poor Prognosis after Corticosteroid- and Ursodeoxycholic Acid-Related Remission of Peripheral and Peribiliary Eosinophilia.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Precision medicine in non-small cell lung cancer (NSCLC) is a rapidly evolving area, with the development of targeted therapies for advanced disease and concomitant molecular testing to inform clinical decision-making. In contrast, routine molecular testing in stage I-III disease has not been required, where standard of care comprises surgery with or without adjuvant or neoadjuvant chemotherapy, or concurrent chemoradiotherapy for unresectable stage III disease, without the integration of targeted therapy. However, the phase 3 ADAURA trial has recently shown that the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), osimertinib, reduces the risk of disease recurrence by 80% versus placebo in the adjuvant setting for patients with stage IB-IIIA EGFR mutation-positive NSCLC following complete tumor resection with or without adjuvant chemotherapy, according to physician and patient choice. Treatment with adjuvant osimertinib requires selection of patients based on the presence of an EGFR-TKI sensitizing mutation. Other targeted agents are currently being evaluated in the adjuvant and neoadjuvant settings. Approval of at least some of these other agents is highly likely in the coming years, bringing with it in parallel, a requirement for comprehensive molecular testing for stage I-III disease. In this review, we consider the implications of integrating molecular testing into practice when managing patients with stage I-III non-squamous NSCLC. We discuss best practices, approaches and challenges from pathology, surgical and oncology perspectives.", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Charu", "last_name": "Aggarwal", "name": null }, { "creator_type": "author", "first_name": "Lukas", "last_name": "Bubendorf", "name": null }, { "creator_type": "author", "first_name": "Wendy A.", "last_name": "Cooper", "name": null }, { "creator_type": "author", "first_name": "Peter", "last_name": "Illei", "name": null }, { "creator_type": "author", "first_name": "Paula", "last_name": "Borralho Nunes", "name": null }, { "creator_type": "author", "first_name": "Boon-Hean", "last_name": "Ong", "name": null }, { "creator_type": "author", "first_name": "Ming-Sound", "last_name": "Tsao", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null }, { "creator_type": "author", "first_name": "Keith M.", "last_name": "Kerr", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.lungcan.2021.09.003" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "34739853" } }, "mesh": [ { "descriptor": "Carcinoma, Non-Small-Cell Lung", "descriptor_ui": "D002289", "major_topic": true }, { "descriptor": "ErbB Receptors", "descriptor_ui": "D066246", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Lung Neoplasms", "descriptor_ui": "D008175", "major_topic": true }, { "descriptor": "Molecular Diagnostic Techniques", "descriptor_ui": "D025202", "major_topic": false }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": false }, { "descriptor": "Neoplasm Recurrence, Local", "descriptor_ui": "D009364", "major_topic": false }, { "descriptor": "Protein Kinase Inhibitors", "descriptor_ui": "D047428", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Dec", "date_precision": "unknown", "issue": "", "normalized_date": null, "pages": "42-53", "proceedings_title": null, "publisher": "", "title": "Lung cancer (Amsterdam, Netherlands)", "volume": "162", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Molecular testing in stage I-III non-small cell lung cancer: Approaches and challenges.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "OBJECTIVES: This study review focuses on a deep learning method for the detection of colorectal lesions in colonoscopy and AI support for detecting colorectal neoplasia, especially in flat lesions. DATA SOURCES: We performed a systematic electric search with PubMed by using \"colonoscopy\", \"artificial intelligence\", and \"detection\". Finally, nine articles about development and validation study and eight clinical trials met the review criteria. RESULTS: Development and validation studies showed that trained AI models had high accuracy-approximately 90% or more for detecting lesions. Performance was better in elevated lesions than in superficial lesions in the two studies. Among the eight clinical trials, all but one trial showed a significantly high adenoma detection rate in the CADe group than in the control group. Interestingly, the CADe group detected significantly high flat lesions than the control group in the seven studies. CONCLUSION: Flat colorectal neoplasia can be detected by endoscopists who use AI.", "classifications": [ { "id": "Hamamoto", "label": "Group Hamamoto", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Masayoshi", "last_name": "Yamada", "name": null }, { "creator_type": "author", "first_name": "Yutaka", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Shigemi", "last_name": "Yamada", "name": null }, { "creator_type": "author", "first_name": "Hiroko", "last_name": "Kondo", "name": null }, { "creator_type": "author", "first_name": "Ryuji", "last_name": "Hamamoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.bpg.2021.101745" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "34172250" } }, "mesh": [ { "descriptor": "Artificial Intelligence", "descriptor_ui": "D001185", "major_topic": false }, { "descriptor": "Colonoscopy", "descriptor_ui": "D003113", "major_topic": false }, { "descriptor": "Colorectal Neoplasms", "descriptor_ui": "D015179", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Jun-Aug", "date_precision": "unknown", "issue": "", "normalized_date": null, "pages": "101745", "proceedings_title": null, "publisher": "", "title": "Best practice & research. Clinical gastroenterology", "volume": "52-53", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Detection of flat colorectal neoplasia by artificial intelligence: A systematic review.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Osteosarcoma is the most common high-grade malignancy of bone, and novel therapeutic options are urgently required. Previously, we developed mouse osteosarcoma AXT cells that can proliferate both under adherent and nonadherent conditions. Based on metabolite levels, nonadherent conditions were more similar to the in vivo environment than adherent conditions. A drug screen identified MEK inhibitors, including trametinib, that preferentially decreased the viability of nonadherent AXT cells. Trametinib inhibited the cell cycle and induced apoptosis in AXT cells, and both effects were stronger under nonadherent conditions. Trametinib also potently decreased viability in U2OS cells, but its effects were less prominent in MG63 or Saos2 cells. By contrast, MG63 and Saos2 cells were more sensitive to PI3K inhibition than AXT or U2OS cells. Notably, the combination of MAPK/ERK kinase (MEK) and PI3K inhibition synergistically decreased viability in U2OS and AXT cells, but this effect was less pronounced in MG63 or Saos2 cells. Therefore, signal dependence for cell survival and crosstalk between MEK-ERK and PI3K-AKT pathways in osteosarcoma are cell context-dependent. The activation status of other kinases including CREB varied in a cell context-dependent manner, which might determine the response to MEK inhibition. A single dose of trametinib was sufficient to decrease the size of the primary tumor and circulating tumor cells in vivo. Moreover, combined administration of trametinib and rapamycin or conventional anticancer drugs further increased antitumor activity. Thus, given optimal biomarkers for predicting its effects, trametinib holds therapeutic potential for the treatment of osteosarcoma.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Takatsune", "last_name": "Shimizu", "name": null }, { "creator_type": "author", "first_name": "Kiyomi", "last_name": "Kimura", "name": null }, { "creator_type": "author", "first_name": "Eiji", "last_name": "Sugihara", "name": null }, { "creator_type": "author", "first_name": "Sayaka", "last_name": "Yamaguchi-Iwai", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Nobusue", "name": null }, { "creator_type": "author", "first_name": "Oltea", "last_name": "Sampetrean", "name": null }, { "creator_type": "author", "first_name": "Yuji", "last_name": "Otsuki", "name": null }, { "creator_type": "author", "first_name": "Yumi", "last_name": "Fukuchi", "name": null }, { "creator_type": "author", "first_name": "Kaori", "last_name": "Saitoh", "name": null }, { "creator_type": "author", "first_name": "Keiko", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Akihiro", "last_name": "Muto", "name": null }, { "creator_type": "author", "first_name": "Hideyuki", "last_name": "Saya", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/jor.25023" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "33751653" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Apoptosis", "descriptor_ui": "D017209", "major_topic": false }, { "descriptor": "Bone Neoplasms", "descriptor_ui": "D001859", "major_topic": true }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Cell Proliferation", "descriptor_ui": "D049109", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mitogen-Activated Protein Kinase Kinases", "descriptor_ui": "D020929", "major_topic": false }, { "descriptor": "Osteosarcoma", "descriptor_ui": "D012516", "major_topic": true }, { "descriptor": "Phosphatidylinositol 3-Kinases", "descriptor_ui": "D019869", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Dec", "date_precision": "unknown", "issue": "12", "normalized_date": null, "pages": "2732-2743", "proceedings_title": null, "publisher": "", "title": "Journal of orthopaedic research : official publication of the Orthopaedic Research Society", "volume": "39", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "MEK inhibition preferentially suppresses anchorage-independent growth in osteosarcoma cells and decreases tumors in vivo.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Tyrosine kinase inhibitors (TKIs) are used as targeted drugs for advanced renal cell carcinoma (RCC), although most cases eventually progress by acquiring resistance. Cancer stemness plays critical roles in tumor aggressiveness and therapeutic resistance, and dipeptidyl peptidase IV (DPP4) has been recently identified as a cancer stemness-related protein. A question arises whether DPP4 contributes to TKI efficacy in RCC. We established patient-derived RCC spheroids and showed that DPP4 expression is associated with stemness-related gene expression. TKI sunitinib resistance was rescued by DPP4 inhibition using sitagliptin or specific siRNAs in RCC cells and tumors. DPP4 expression can be inducible by retinoic acid and repressed by ALDH1A inhibition. Among type 2 diabetes patients with clinical RCC tumors, higher TKI efficacy is observed in those bearing DPP4(high) tumors treated with DPP4 inhibitors. This study provides new insights into TKI resistance and drug repositioning of DPP4 inhibitor as a promising strategy for advanced RCC.", "classifications": [ { "id": "Okamoto", "label": "Group Okamoto", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Shuhei", "last_name": "Kamada", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Namekawa", "name": null }, { "creator_type": "author", "first_name": "Kazuhiro", "last_name": "Ikeda", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Kagawa", "name": null }, { "creator_type": "author", "first_name": "Hideki", "last_name": "Takeshita", "name": null }, { "creator_type": "author", "first_name": "Akihiro", "last_name": "Yano", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Okamoto", "name": null }, { "creator_type": "author", "first_name": "Tomohiko", "last_name": "Ichikawa", "name": null }, { "creator_type": "author", "first_name": "Kuniko", "last_name": "Horie-Inoue", "name": null }, { "creator_type": "author", "first_name": "Satoru", "last_name": "Kawakami", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Inoue", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41388-021-01822-5" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "33972682" } }, "mesh": [ { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Aged, 80 and over", "descriptor_ui": "D000369", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Carcinoma, Renal Cell", "descriptor_ui": "D002292", "major_topic": false }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Diabetes Mellitus, Type 2", "descriptor_ui": "D003924", "major_topic": false }, { "descriptor": "Dipeptidyl Peptidase 4", "descriptor_ui": "D018819", "major_topic": false }, { "descriptor": "Dipeptidyl-Peptidase IV Inhibitors", "descriptor_ui": "D054873", "major_topic": false }, { "descriptor": "Drug Resistance, Neoplasm", "descriptor_ui": "D019008", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Kidney Neoplasms", "descriptor_ui": "D007680", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred BALB C", "descriptor_ui": "D008807", "major_topic": false }, { "descriptor": "Mice, Nude", "descriptor_ui": "D008819", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Protein Kinase Inhibitors", "descriptor_ui": "D047428", "major_topic": false }, { "descriptor": "Sitagliptin Phosphate", "descriptor_ui": "D000068900", "major_topic": false }, { "descriptor": "Spheroids, Cellular", "descriptor_ui": "D018874", "major_topic": false }, { "descriptor": "Sunitinib", "descriptor_ui": "D000077210", "major_topic": false }, { "descriptor": "Survival Rate", "descriptor_ui": "D015996", "major_topic": false }, { "descriptor": "Xenograft Model Antitumor Assays", "descriptor_ui": "D023041", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Jun", "date_precision": "unknown", "issue": "22", "normalized_date": null, "pages": "3899-3913", "proceedings_title": null, "publisher": "", "title": "Oncogene", "volume": "40", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Functional inhibition of cancer stemness-related protein DPP4 rescues tyrosine kinase inhibitor resistance in renal cell carcinoma.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "In recent years, the use of organosulfones as a new class of cross-coupling partner in transition-metal catalyzed reactions has undergone significant advancement. In this personal account, our recent investigations into desulfonylative cross-coupling reactions of benzylic sulfone derivatives catalyzed by Pd, Ni, and Cu catalysis is described. Combined with the facile alpha-functionalizations of sulfones, our methods can be used to form valuable multiply-arylated structures such as di-, tri-, and, tetraarylmethanes from readily available substrates. The reactivity of sulfones can be increased by introducing electron-withdrawing substituents such as 3,5-bis(trifluoromethyl)phenyl and trifluoromethyl groups, which enable more challenging cross-coupling reactions. Reactive intermediates including Cu-carbene complexes were identified as key intermediates in sulfone activation, representing new types of C-SO(2) bond activation processes. These results indicate sulfones are powerful functional groups, enabling new catalytic desulfonylative transformations.", "classifications": [ { "id": "Nanbo", "label": "Group Nanbo", "parent": "Tsuchiya", "type": "group" }, { "id": "Tsuchiya", "label": "Team Tsuchiya", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Masakazu", "last_name": "Nambo", "name": null }, { "creator_type": "author", "first_name": "Cathleen M.", "last_name": "Crudden", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/tcr.202100210" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "34523788" } }, "mesh": [], "publication": { "conference_name": null, "date": "2021 Dec", "date_precision": "unknown", "issue": "12", "normalized_date": null, "pages": "3978-3989", "proceedings_title": null, "publisher": "", "title": "Chemical record (New York, N.Y.)", "volume": "21", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Transition Metal-Catalyzed Cross-Couplings of Benzylic Sulfone Derivatives.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Merkel cell carcinoma (MCC) is a rare cutaneous neuroendocrine carcinoma that tends to show local recurrence and metastasis. Typically, MCC is polyomavirus (MCPyV)-associated and cytokeratin 20 (CK20) positive. However, little is known about this tumor and its origins. Here, we aimed to determine the developmental origins of MCC and to identify prognostic clinicopathologic factors. Initial examinations revealed that CK20 and MCPyV expression (CK20+, MCPyV+ (60%); CK20+, MCPyV- (10%); CK20-, and MCPyV- (30%)) did not affect overall survival. With RB1 gene sequencing of FFPE specimens, which covered an entire exon, all RB1 mutation-positive cases showed positive regional lymph node and/or distant metastases (8/8 cases, 100%), whereas the frequency of the metastasis was statistically significantly lower in RB1 mutation-negative cases, (10/16 cases, 62%, P = 0.033). The results were also confirmed with immunohistochemistry, and either RB1 alterations, entire exon sequencing, or immunohistochemistry was associated with the metastasis (P = 0.007). RB1 alterations may be used to access the aggressive clinical course of MCC.", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yusuke", "last_name": "Muto", "name": null }, { "creator_type": "author", "first_name": "Eijitsu", "last_name": "Ryo", "name": null }, { "creator_type": "author", "first_name": "Kenjiro", "last_name": "Namikawa", "name": null }, { "creator_type": "author", "first_name": "Akira", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Dai", "last_name": "Ogata", "name": null }, { "creator_type": "author", "first_name": "Taku", "last_name": "Fujimura", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null }, { "creator_type": "author", "first_name": "Setsuya", "last_name": "Aiba", "name": null }, { "creator_type": "author", "first_name": "Naoya", "last_name": "Yamazaki", "name": null }, { "creator_type": "author", "first_name": "Taisuke", "last_name": "Mori", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/pin.13090" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "33751708" } }, "mesh": [ { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Aged, 80 and over", "descriptor_ui": "D000369", "major_topic": false }, { "descriptor": "Carcinoma, Merkel Cell", "descriptor_ui": "D015266", "major_topic": true }, { "descriptor": "Carcinoma, Neuroendocrine", "descriptor_ui": "D018278", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "High-Throughput Nucleotide Sequencing", "descriptor_ui": "D059014", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Immunochemistry", "descriptor_ui": "D007120", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": false }, { "descriptor": "Neoplasm Metastasis", "descriptor_ui": "D009362", "major_topic": false }, { "descriptor": "Neoplasm Recurrence, Local", "descriptor_ui": "D009364", "major_topic": false }, { "descriptor": "Prognosis", "descriptor_ui": "D011379", "major_topic": true }, { "descriptor": "Retinoblastoma Binding Proteins", "descriptor_ui": "D056286", "major_topic": true }, { "descriptor": "Ubiquitin-Protein Ligases", "descriptor_ui": "D044767", "major_topic": true } ], "publication": { "conference_name": null, "date": "2021 May", "date_precision": "unknown", "issue": "5", "normalized_date": null, "pages": "337-347", "proceedings_title": null, "publisher": "", "title": "Pathology international", "volume": "71", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "RB1 gene mutations are a distinct predictive factor in Merkel cell carcinoma.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: BCR-ABL1 tyrosine kinase inhibitors (TKIs) are commonly initiated in older patients with chronic myeloid leukaemia in the chronic phase at standard doses. However, because of their safety profile in this population, appropriate therapy has not been established. We aimed to investigate whether a lower than standard dose of dasatinib was an appropriate therapy for older patients with chronic myeloid leukaemia in the chronic phase. METHODS: DAsatinib, Very Low-dose, for Elderly CML-CP patients (DAVLEC) was a multicentre, single-arm, phase 2 trial done in 25 Japanese hospitals. We enrolled patients older than 70 years with newly diagnosed chronic myeloid leukaemia in the chronic phase, ECOG performance status 0-2, and no previous treatment for CML other than hydroxyurea within 4 weeks. Second-generation TKI dasatinib was given orally at a starting dose of 20% of the standard dose (20 mg/day). If the treatment was assessed as optimal response at 3 months, 6 months, and 9 months and adverse events were grade 2 or better (according to the NCI Common Toxicity Criteria v 4.0), the same dose was continued. If response was suboptimal and adverse events were grade 2 or better, the dose was increased by 20 mg/day. Once a dose reduction had been made because of a grade 3 or worse adverse event, there were no further dose increases. Treatment was discontinued if assessed as failure (disease progression to the accelerated phase or acute phase). The primary endpoint was the achievement of major molecular response at 12 months, assessed using a per-protocol analysis. This trial is registered at with the UMIN clinical trial registry, UMIN000024548, and has completed its planned observation period. FINDINGS: Between Nov 1, 2016, and Oct 30, 2019, 52 patients received first-line dasatinib therapy at 20 mg/day. The median age at diagnosis was 77.5 years (73.5-83.0). 35 (67%) patients were male and 17 (33%) were female. 31 (60%) of 52 patients reached major molecular response at 12 months (one-sided 95% CI 48-71), with a median follow-up of 366 days (IQR 353-372). Grade 3-4 adverse events were reported in 12 (23%) patients. Neutropenia was the most frequent grade 3-4 adverse event, occurring in three (6%) patients. No treatment-related deaths were observed. INTERPRETATION: Low-dose dasatinib at 20mg/day is worthy of consideration as a starting dose for older patients with newly diagnosed chronic myeloid leukaemia in the chronic phase. However, this dose needs to be further studied in a larger cohort and with a more ethnically diverse population. FUNDING: Bristol-Myers Squibb.", "classifications": [ { "id": "Tanaka", "label": "Group Tanaka", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Kazunori", "last_name": "Murai", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Ureshino", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Kumagai", "name": null }, { "creator_type": "author", "first_name": "Hideo", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Kaichi", "last_name": "Nishiwaki", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Wakita", "name": null }, { "creator_type": "author", "first_name": "Koiti", "last_name": "Inokuchi", "name": null }, { "creator_type": "author", "first_name": "Toshihiro", "last_name": "Fukushima", "name": null }, { "creator_type": "author", "first_name": "Chikashi", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Nobuhiko", "last_name": "Uoshima", "name": null }, { "creator_type": "author", "first_name": "Toru", "last_name": "Kiguchi", "name": null }, { "creator_type": "author", "first_name": "Masayuki", "last_name": "Mita", "name": null }, { "creator_type": "author", "first_name": "Jun", "last_name": "Aoki", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Kimura", "name": null }, { "creator_type": "author", "first_name": "Kaori", "last_name": "Karimata", "name": null }, { "creator_type": "author", "first_name": "Kensuke", "last_name": "Usuki", "name": null }, { "creator_type": "author", "first_name": "Joji", "last_name": "Shimono", "name": null }, { "creator_type": "author", "first_name": "Yoshiaki", "last_name": "Chinen", "name": null }, { "creator_type": "author", "first_name": "Junya", "last_name": "Kuroda", "name": null }, { "creator_type": "author", "first_name": "Yasufumi", "last_name": "Matsuda", "name": null }, { "creator_type": "author", "first_name": "Kensuke", "last_name": "Nakao", "name": null }, { "creator_type": "author", "first_name": "Takaaki", "last_name": "Ono", "name": null }, { "creator_type": "author", "first_name": "Katsumichi", "last_name": "Fujimaki", "name": null }, { "creator_type": "author", "first_name": "Hirohiko", "last_name": "Shibayama", "name": null }, { "creator_type": "author", "first_name": "Chisaki", "last_name": "Mizumoto", "name": null }, { "creator_type": "author", "first_name": "Tomoharu", "last_name": "Takeoka", "name": null }, { "creator_type": "author", "first_name": "Katsuhiro", "last_name": "Io", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Kondo", "name": null }, { "creator_type": "author", "first_name": "Masatomo", "last_name": "Miura", "name": null }, { "creator_type": "author", "first_name": "Yousuke", "last_name": "Minami", "name": null }, { "creator_type": "author", "first_name": "Takayuki", "last_name": "Ikezoe", "name": null }, { "creator_type": "author", "first_name": "Jun", "last_name": "Imagawa", "name": null }, { "creator_type": "author", "first_name": "Ayako", "last_name": "Takamori", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Kawaguchi", "name": null }, { "creator_type": "author", "first_name": "Junichi", "last_name": "Sakamoto", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Kimura", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/s2352-3026(21)00333-1" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "34826413" } }, "mesh": [ { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Dasatinib", "descriptor_ui": "D000069439", "major_topic": false }, { "descriptor": "Drug Administration Schedule", "descriptor_ui": "D004334", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Fusion Proteins, bcr-abl", "descriptor_ui": "D016044", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Leukemia, Myelogenous, Chronic, BCR-ABL Positive", "descriptor_ui": "D015464", "major_topic": true }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Treatment Outcome", "descriptor_ui": "D016896", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Dec", "date_precision": "unknown", "issue": "12", "normalized_date": null, "pages": "e902-e911", "proceedings_title": null, "publisher": "", "title": "The Lancet. Haematology", "volume": "8", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Low-dose dasatinib in older patients with chronic myeloid leukaemia in chronic phase (DAVLEC): a single-arm, multicentre, phase 2 trial.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Tissue stem cells are generated from a population of embryonic progenitors through organ-specific morphogenetic events(1,2). Although tissue stem cells are central to organ homeostasis and regeneration, it remains unclear how they are induced during development, mainly because of the lack of markers that exclusively label prospective stem cells. Here we combine marker-independent long-term 3D live imaging and single-cell transcriptomics to capture a dynamic lineage progression and transcriptome changes in the entire epithelium of the mouse hair follicle as it develops. We found that the precursors of different epithelial lineages were aligned in a 2D concentric manner in the basal layer of the hair placode. Each concentric ring acquired unique transcriptomes and extended to form longitudinally aligned, 3D cylindrical compartments. Prospective bulge stem cells were derived from the peripheral ring of the placode basal layer, but not from suprabasal cells (as was previously suggested(3)). The fate of placode cells is determined by the cell position, rather than by the orientation of cell division. We also identified 13 gene clusters: the ensemble expression dynamics of these clusters drew the entire transcriptional landscape of epithelial lineage diversification, consistent with cell lineage data. Combining these findings with previous work on the development of appendages in insects(4,5), we describe the 'telescope model', a generalized model for the development of ectodermal organs in which 2D concentric zones in the placode telescope out to form 3D longitudinally aligned cylindrical compartments.", "classifications": [ { "id": "Fujiwara", "label": "Group Fujiwara", "parent": "Fujiwara", "type": "group" }, { "id": "Nikaido", "label": "Group Nikaido", "parent": "Fujiwara", "type": "group" }, { "id": "Fujiwara", "label": "Team Fujiwara", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Ritsuko", "last_name": "Morita", "name": null }, { "creator_type": "author", "first_name": "Noriko", "last_name": "Sanzen", "name": null }, { "creator_type": "author", "first_name": "Hiroko", "last_name": "Sasaki", "name": null }, { "creator_type": "author", "first_name": "Tetsutaro", "last_name": "Hayashi", "name": null }, { "creator_type": "author", "first_name": "Mana", "last_name": "Umeda", "name": null }, { "creator_type": "author", "first_name": "Mika", "last_name": "Yoshimura", "name": null }, { "creator_type": "author", "first_name": "Takaki", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Tatsuo", "last_name": "Shibata", "name": null }, { "creator_type": "author", "first_name": "Takaya", "last_name": "Abe", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Kiyonari", "name": null }, { "creator_type": "author", "first_name": "Yasuhide", "last_name": "Furuta", "name": null }, { "creator_type": "author", "first_name": "Itoshi", "last_name": "Nikaido", "name": null }, { "creator_type": "author", "first_name": "Hironobu", "last_name": "Fujiwara", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41586-021-03638-5" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "34108685" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Lineage", "descriptor_ui": "D019070", "major_topic": true }, { "descriptor": "Cell Tracking", "descriptor_ui": "D058948", "major_topic": false }, { "descriptor": "Ectoderm", "descriptor_ui": "D004475", "major_topic": false }, { "descriptor": "Embryo, Mammalian", "descriptor_ui": "D004622", "major_topic": false }, { "descriptor": "Epithelial Cells", "descriptor_ui": "D004847", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Flow Cytometry", "descriptor_ui": "D005434", "major_topic": false }, { "descriptor": "Gene Expression Regulation, Developmental", "descriptor_ui": "D018507", "major_topic": false }, { "descriptor": "Hair Follicle", "descriptor_ui": "D018859", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Transgenic", "descriptor_ui": "D008822", "major_topic": false }, { "descriptor": "Multigene Family", "descriptor_ui": "D005810", "major_topic": false }, { "descriptor": "RNA-Seq", "descriptor_ui": "D000081246", "major_topic": false }, { "descriptor": "Single-Cell Analysis", "descriptor_ui": "D059010", "major_topic": false }, { "descriptor": "Skin", "descriptor_ui": "D012867", "major_topic": false }, { "descriptor": "Stem Cells", "descriptor_ui": "D013234", "major_topic": false }, { "descriptor": "Tissue Culture Techniques", "descriptor_ui": "D046509", "major_topic": false }, { "descriptor": "Transcriptome", "descriptor_ui": "D059467", "major_topic": false }, { "descriptor": "Vibrissae", "descriptor_ui": "D014738", "major_topic": false } ], "publication": { "conference_name": null, "date": "2021 Jun", "date_precision": "unknown", "issue": "7864", "normalized_date": null, "pages": "547-552", "proceedings_title": null, "publisher": "", "title": "Nature", "volume": "594", "year": 2021 }, "ssbd": { "database": [], "repository": [ "ssbd-repos-000149" ] }, "title": "Tracing the origin of hair follicle stem cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "", "classifications": [ { "id": "Akaike", "label": "Group Akaike", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Kazufumi", "last_name": "Honda", "name": null }, { "creator_type": "author", "first_name": "Takako", "last_name": "Hishiki", "name": null }, { "creator_type": "author", "first_name": "Sohei", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Takehiro", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Nami", "last_name": "Miura", "name": null }, { "creator_type": "author", "first_name": "Akiko", "last_name": "Kubo", "name": null }, { "creator_type": "author", "first_name": "Mai", "last_name": "Itoh", "name": null }, { "creator_type": "author", "first_name": "Wei-Yu", "last_name": "Chen", "name": null }, { "creator_type": "author", "first_name": "Masashi", "last_name": "Takano", "name": null }, { "creator_type": "author", "first_name": "Tomoyuki", "last_name": "Yoshikawa", "name": null }, { "creator_type": "author", "first_name": "Takahiro", "last_name": "Kasamatsu", "name": null }, { "creator_type": "author", "first_name": "Shinichiro", "last_name": "Sonoda", "name": null }, { "creator_type": "author", "first_name": "Hirotoshi", "last_name": "Yoshizawa", "name": null }, { "creator_type": "author", "first_name": "Seigo", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Yuichiro", "last_name": "Itai", "name": null }, { "creator_type": "author", "first_name": "Megumi", "last_name": "Shiota", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Koike", "name": null }, { "creator_type": "author", "first_name": "Masayuki", "last_name": "Naya", "name": null }, { "creator_type": "author", "first_name": "Noriyo", "last_name": "Hayakawa", "name": null }, { "creator_type": "author", "first_name": "Yoshiko", "last_name": "Naito", "name": null }, { "creator_type": "author", "first_name": "Tomomi", "last_name": "Matsuura", "name": null }, { "creator_type": "author", "first_name": "Keiko", "last_name": "Iwaisako", "name": null }, { "creator_type": "author", "first_name": "Toshihiko", "last_name": "Masui", "name": null }, { "creator_type": "author", "first_name": "Shinji", "last_name": "Uemoto", "name": null }, { "creator_type": "author", "first_name": "Kengo", "last_name": "Nagashima", "name": null }, { "creator_type": "author", "first_name": "Yoshinori", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Tomohiro", "last_name": "Sakuma", "name": null }, { "creator_type": "author", "first_name": "Osamu", "last_name": "Matsubara", "name": null }, { "creator_type": "author", "first_name": "Wilber", "last_name": "Huang", "name": null }, { "creator_type": "author", "first_name": "Tomoaki", "last_name": "Ida", "name": null }, { "creator_type": "author", "first_name": "Takaaki", "last_name": "Akaike", "name": null }, { "creator_type": "author", "first_name": "Yohei", "last_name": "Masugi", "name": null }, { "creator_type": "author", "first_name": "Michiie", "last_name": "Sakamoto", "name": null }, { "creator_type": "author", "first_name": "Tomoyasu", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Yoshinori", "last_name": "Ino", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Tsuda", "name": null }, { "creator_type": "author", "first_name": "Nobuyoshi", "last_name": "Hiraoka", "name": null }, { "creator_type": "author", "first_name": "Yasuaki", "last_name": "Kabe", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Suematsu", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.redox.2021.102028" }, "pmcid": { "normalized": "PMC8182420" }, "pmid": { "normalized": "34087755" } }, "mesh": [], "publication": { "conference_name": null, "date": "2021 Aug", "date_precision": "unknown", "issue": "", "normalized_date": null, "pages": "102028", "proceedings_title": null, "publisher": "", "title": "Redox biology", "volume": "44", "year": 2021 }, "ssbd": { "database": [], "repository": [] }, "title": "Corrigendum to On-tissue polysulfide visualization by surface-enhanced Raman spectroscopy benefits patients with ovarian cancer to predict post-operative chemosensitivity\" [Redox Biol. 41 (2021) 101926].", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "In most dicotyledonous plants, leaf pavement cells exhibit complex jigsaw puzzle-like cell morphogenesis during leaf expansion. Although detailed molecular biological information and mathematical modeling of this jigsaw puzzle-like cell morphogenesis are now available, a full understanding of this process remains elusive. Recent reports have highlighted the importance of three-dimensional (3D) structures (i.e., anticlinal and periclinal cell wall) in understanding the mechanical models that describe this morphogenetic process. We believe that it is important to acquire 3D shapes of pavement cells over time, i.e., acquire and analyze four-dimensional (4D) information when studying the relationship between mechanical modeling and simulations and the actual cell shape. In this report, we have developed a framework to capture and analyze 4D morphological information of Arabidopsis thaliana cotyledon pavement cells by using both direct water immersion observations and computational image analyses, including segmentation, surface modeling, virtual reality and morphometry. The 4D cell models allowed us to perform time-lapse 3D morphometrical analysis, providing detailed quantitative information about changes in cell growth rate and shape, with cellular complexity observed to increase during cell growth. The framework should enable analysis of various phenotypes (e.g., mutants) in greater detail, especially in the 3D deformation of the cotyledon surface, and evaluation of theoretical models that describe pavement cell morphogenesis using computational simulations. Additionally, our accurate and high-throughput acquisition of growing cell structures should be suitable for use in generating in silico model cell structures.", "classifications": [ { "id": "Higaki", "label": "Group Higaki", "parent": "Ueda", "type": "group" }, { "id": "Ueda", "label": "Team Ueda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Takumi", "last_name": "Higaki", "name": null }, { "creator_type": "author", "first_name": "Hidenobu", "last_name": "Mizuno", "name": null } ], "identifiers": { "doi": { "normalized": "10.5511/plantbiotechnology.20.0605a" }, "pmcid": { "normalized": "PMC8034702" }, "pmid": { "normalized": "33850430" } }, "mesh": [], "publication": { "conference_name": null, "date": "2020 Dec 25", "date_precision": "day", "issue": "4", "normalized_date": "2020-12-25", "pages": "429-435", "proceedings_title": null, "publisher": "", "title": "Plant biotechnology (Tokyo, Japan)", "volume": "37", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Four-dimensional imaging with virtual reality to quantitatively explore jigsaw puzzle-like morphogenesis of Arabidopsis cotyledon pavement cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The evaluation of cytoskeletal bundling is a fundamental experimental method in the field of cell biology. Although the skewness of the pixel intensity distribution derived from fluorescently-labeled cytoskeletons has been widely used as a metric to evaluate the degree of bundling in digital microscopy images, its versatility has not been fully validated. Here, we applied the coefficient of variation (CV) of intensity values as an alternative metric, and compared its performance with skewness. In synthetic images representing extremely bundled conditions, the CV successfully detected degrees of bundling that could not be distinguished by skewness. On actual microscopy images, CV was better than skewness, especially on variable-angle epifluorescence microscopic images or stimulated emission depletion and confocal microscopy images of very small areas of around 1 mum(2). When blur or noise was added to synthetic images, CV was found to be robust to blur but deleteriously affected by noise, whereas skewness was robust to noise but deleteriously affected by blur. For confocal images, CV and skewness showed similar sensitivity to noise, possibly because optical blurring is often present in microscopy images. Therefore, in practical use with actual microscopy images, CV may be more appropriate than skewness, unless the image is extremely noisy.", "classifications": [ { "id": "Higaki", "label": "Group Higaki", "parent": "Ueda", "type": "group" }, { "id": "Ueda", "label": "Team Ueda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Takumi", "last_name": "Higaki", "name": null }, { "creator_type": "author", "first_name": "Kae", "last_name": "Akita", "name": null }, { "creator_type": "author", "first_name": "Kaoru", "last_name": "Katoh", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41598-020-79136-x" }, "pmcid": { "normalized": "PMC7752905" }, "pmid": { "normalized": "33349642" } }, "mesh": [ { "descriptor": "Actin Cytoskeleton", "descriptor_ui": "D008841", "major_topic": false }, { "descriptor": "Analysis of Variance", "descriptor_ui": "D000704", "major_topic": false }, { "descriptor": "Arabidopsis", "descriptor_ui": "D017360", "major_topic": false }, { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "Cytoskeleton", "descriptor_ui": "D003599", "major_topic": false }, { "descriptor": "Image Processing, Computer-Assisted", "descriptor_ui": "D007091", "major_topic": false }, { "descriptor": "Laser Scanning Cytometry", "descriptor_ui": "D047569", "major_topic": false }, { "descriptor": "Microscopy, Confocal", "descriptor_ui": "D018613", "major_topic": false }, { "descriptor": "Microscopy, Fluorescence", "descriptor_ui": "D008856", "major_topic": false }, { "descriptor": "Nicotiana", "descriptor_ui": "D014026", "major_topic": false }, { "descriptor": "Plants, Genetically Modified", "descriptor_ui": "D030821", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020 Dec 21", "date_precision": "day", "issue": "1", "normalized_date": "2020-12-21", "pages": "22187", "proceedings_title": null, "publisher": "", "title": "Scientific reports", "volume": "10", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Coefficient of variation as an image-intensity metric for cytoskeleton bundling.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Single-cell transcriptome analysis has been revolutionized by DNA barcodes that index cDNA libraries, allowing highly multiplexed analyses to be performed. Furthermore, DNA barcodes are being leveraged for spatial transcriptomes. Although spatial resolution relies on methods used to decode DNA barcodes, achieving single-molecule decoding remains a challenge. Here, we developed an in-house sequencing system inspired by a single-molecule sequencing system, HeliScope, to spatially decode DNA barcode molecules at single-molecule resolution. We benchmarked our system with 30 types of DNA barcode molecules and obtained an average read length of ~20 nt with an error rate of less than 5% per nucleotide, which was sufficient to spatially identify them. Additionally, we spatially identified DNA barcode molecules bound to antibodies at single-molecule resolution. Leveraging this, we devised a method, termed \"molecular foot printing\", showing potential for applying our system not only to spatial transcriptomics, but also to spatial proteomics.", "classifications": [ { "id": "Shintaku", "label": "Group Shintaku", "parent": "Shintaku", "type": "group" }, { "id": "Shintaku", "label": "Team Shintaku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yusuke", "last_name": "Oguchi", "name": null }, { "creator_type": "author", "first_name": "Hirofumi", "last_name": "Shintaku", "name": null }, { "creator_type": "author", "first_name": "Sotaro", "last_name": "Uemura", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s42003-020-01499-8" }, "pmcid": { "normalized": "PMC7749132" }, "pmid": { "normalized": "33339962" } }, "mesh": [ { "descriptor": "DNA Barcoding, Taxonomic", "descriptor_ui": "D058893", "major_topic": false }, { "descriptor": "Gene Expression Profiling", "descriptor_ui": "D020869", "major_topic": false }, { "descriptor": "Gene Library", "descriptor_ui": "D015723", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "K562 Cells", "descriptor_ui": "D020014", "major_topic": false }, { "descriptor": "Sequence Analysis, DNA", "descriptor_ui": "D017422", "major_topic": false }, { "descriptor": "Single Molecule Imaging", "descriptor_ui": "D000072760", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020 Dec 18", "date_precision": "day", "issue": "1", "normalized_date": "2020-12-18", "pages": "788", "proceedings_title": null, "publisher": "", "title": "Communications biology", "volume": "3", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Development of a sequencing system for spatial decoding of DNA barcode molecules at single-molecule resolution.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The application of segmentation methods to medical imaging has the potential to create novel diagnostic support models. With respect to fetal ultrasound, the thoracic wall is a key structure on the assessment of the chest region for examiners to recognize the relative orientation and size of structures inside the thorax, which are critical components in neonatal prognosis. In this study, to improve the segmentation performance of the thoracic wall in fetal ultrasound videos, we proposed a novel model-agnostic method using deep learning techniques: the Multi-Frame + Cylinder method (MFCY). The Multi-frame method (MF) uses time-series information of ultrasound videos, and the Cylinder method (CY) utilizes the shape of the thoracic wall. To evaluate the achieved improvement, we performed segmentation using five-fold cross-validation on 538 ultrasound frames in the four-chamber view (4CV) of 256 normal cases using U-net and DeepLabv3+. MFCY increased the mean values of the intersection over union (IoU) of thoracic wall segmentation from 0.448 to 0.493 for U-net and from 0.417 to 0.470 for DeepLabv3+. These results demonstrated that MFCY improved the segmentation performance of the thoracic wall in fetal ultrasound videos without altering the network structure. MFCY is expected to facilitate the development of diagnostic support models in fetal ultrasound by providing further accurate segmentation of the thoracic wall.", "classifications": [ { "id": "Hamamoto", "label": "Group Hamamoto", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Kanto", "last_name": "Shozu", "name": null }, { "creator_type": "author", "first_name": "Masaaki", "last_name": "Komatsu", "name": null }, { "creator_type": "author", "first_name": "Akira", "last_name": "Sakai", "name": null }, { "creator_type": "author", "first_name": "Reina", "last_name": "Komatsu", "name": null }, { "creator_type": "author", "first_name": "Ai", "last_name": "Dozen", "name": null }, { "creator_type": "author", "first_name": "Hidenori", "last_name": "Machino", "name": null }, { "creator_type": "author", "first_name": "Suguru", "last_name": "Yasutomi", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Arakaki", "name": null }, { "creator_type": "author", "first_name": "Ken", "last_name": "Asada", "name": null }, { "creator_type": "author", "first_name": "Syuzo", "last_name": "Kaneko", "name": null }, { "creator_type": "author", "first_name": "Ryu", "last_name": "Matsuoka", "name": null }, { "creator_type": "author", "first_name": "Akitoshi", "last_name": "Nakashima", "name": null }, { "creator_type": "author", "first_name": "Akihiko", "last_name": "Sekizawa", "name": null }, { "creator_type": "author", "first_name": "Ryuji", "last_name": "Hamamoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.3390/biom10121691" }, "pmcid": { "normalized": "PMC7766150" }, "pmid": { "normalized": "33348873" } }, "mesh": [ { "descriptor": "Algorithms", "descriptor_ui": "D000465", "major_topic": false }, { "descriptor": "Artificial Intelligence", "descriptor_ui": "D001185", "major_topic": false }, { "descriptor": "Computational Biology", "descriptor_ui": "D019295", "major_topic": false }, { "descriptor": "Heart", "descriptor_ui": "D006321", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Image Processing, Computer-Assisted", "descriptor_ui": "D007091", "major_topic": false }, { "descriptor": "Machine Learning", "descriptor_ui": "D000069550", "major_topic": false }, { "descriptor": "Models, Statistical", "descriptor_ui": "D015233", "major_topic": false }, { "descriptor": "Neural Networks, Computer", "descriptor_ui": "D016571", "major_topic": false }, { "descriptor": "Prenatal Diagnosis", "descriptor_ui": "D011296", "major_topic": false }, { "descriptor": "Prognosis", "descriptor_ui": "D011379", "major_topic": false }, { "descriptor": "Thoracic Wall", "descriptor_ui": "D035441", "major_topic": false }, { "descriptor": "Ultrasonography, Prenatal", "descriptor_ui": "D016216", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020 Dec 17", "date_precision": "day", "issue": "12", "normalized_date": "2020-12-17", "pages": "", "proceedings_title": null, "publisher": "", "title": "Biomolecules", "volume": "10", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Model-Agnostic Method for Thoracic Wall Segmentation in Fetal Ultrasound Videos.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The histone methyltransferase SETD8, which methylates the lysine 20 of histone H4 (H4K20), is reportedly involved in human carcinogenesis along with nonhistone proteins such as p53. However, its expression profiles and functions in the context of high-grade serous ovarian carcinoma (HGSOC) are still unknown. The purpose of this study was to investigate the role of SETD8 in HGSOC. We performed quantitative real-time PCR and immunohistochemistry to detect the expression of SETD8 in HGSOC samples and normal ovarian specimens. Then, we assessed the effect of the inhibition of SETD8 expression using small interfering RNA (siRNA) and a selective inhibitor (UNC0379) on cell proliferation and apoptosis in HGSOC cells. The expression of SETD8 was significantly upregulated in clinical ovarian cancer specimens compared to that in the corresponding normal ovary. In addition, suppression of SETD8 expression in HGSOC cells with either siRNA or UNC0379 resulted in reduced levels of H4K20 monomethylation, inhibition of cell proliferation, and induction of apoptosis. Furthermore, UNC0379 showed a long-term antitumor effect against HGSOC cells, as demonstrated by colony-formation assays. SETD8 thus constitutes a promising therapeutic target for HGSOC, warranting further functional studies.", "classifications": [ { "id": "Hamamoto", "label": "Group Hamamoto", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Miku", "last_name": "Wada", "name": null }, { "creator_type": "author", "first_name": "Asako", "last_name": "Kukita", "name": null }, { "creator_type": "author", "first_name": "Kenbun", "last_name": "Sone", "name": null }, { "creator_type": "author", "first_name": "Ryuji", "last_name": "Hamamoto", "name": null }, { "creator_type": "author", "first_name": "Syuzo", "last_name": "Kaneko", "name": null }, { "creator_type": "author", "first_name": "Masaaki", "last_name": "Komatsu", "name": null }, { "creator_type": "author", "first_name": "Yu", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Futaba", "last_name": "Inoue", "name": null }, { "creator_type": "author", "first_name": "Machiko", "last_name": "Kojima", "name": null }, { "creator_type": "author", "first_name": "Harunori", "last_name": "Honjoh", "name": null }, { "creator_type": "author", "first_name": "Ayumi", "last_name": "Taguchi", "name": null }, { "creator_type": "author", "first_name": "Tomoko", "last_name": "Kashiyama", "name": null }, { "creator_type": "author", "first_name": "Yuichiro", "last_name": "Miyamoto", "name": null }, { "creator_type": "author", "first_name": "Michihiro", "last_name": "Tanikawa", "name": null }, { "creator_type": "author", "first_name": "Tetsushi", "last_name": "Tsuruga", "name": null }, { "creator_type": "author", "first_name": "Mayuyo", "last_name": "Mori-Uchino", "name": null }, { "creator_type": "author", "first_name": "Osamu", "last_name": "Wada-Hiraike", "name": null }, { "creator_type": "author", "first_name": "Yutaka", "last_name": "Osuga", "name": null }, { "creator_type": "author", "first_name": "Tomoyuki", "last_name": "Fujii", "name": null } ], "identifiers": { "doi": { "normalized": "10.3390/biom10121686" }, "pmcid": { "normalized": "PMC7766894" }, "pmid": { "normalized": "33339442" } }, "mesh": [ { "descriptor": "Apoptosis", "descriptor_ui": "D017209", "major_topic": false }, { "descriptor": "Cell Cycle", "descriptor_ui": "D002453", "major_topic": false }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Cell Proliferation", "descriptor_ui": "D049109", "major_topic": false }, { "descriptor": "Cell Survival", "descriptor_ui": "D002470", "major_topic": false }, { "descriptor": "Disease Progression", "descriptor_ui": "D018450", "major_topic": false }, { "descriptor": "DNA Methylation", "descriptor_ui": "D019175", "major_topic": false }, { "descriptor": "Epigenesis, Genetic", "descriptor_ui": "D044127", "major_topic": true }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Gene Expression Regulation, Neoplastic", "descriptor_ui": "D015972", "major_topic": true }, { "descriptor": "Histone-Lysine N-Methyltransferase", "descriptor_ui": "D011495", "major_topic": false }, { "descriptor": "Histones", "descriptor_ui": "D006657", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Inhibitory Concentration 50", "descriptor_ui": "D020128", "major_topic": false }, { "descriptor": "Lysine", "descriptor_ui": "D008239", "major_topic": false }, { "descriptor": "Ovarian Neoplasms", "descriptor_ui": "D010051", "major_topic": false }, { "descriptor": "Prognosis", "descriptor_ui": "D011379", "major_topic": false }, { "descriptor": "Quinazolines", "descriptor_ui": "D011799", "major_topic": false }, { "descriptor": "RNA, Small Interfering", "descriptor_ui": "D034741", "major_topic": false }, { "descriptor": "Transfection", "descriptor_ui": "D014162", "major_topic": false }, { "descriptor": "Up-Regulation", "descriptor_ui": "D015854", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020 Dec 16", "date_precision": "day", "issue": "12", "normalized_date": "2020-12-16", "pages": "", "proceedings_title": null, "publisher": "", "title": "Biomolecules", "volume": "10", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Epigenetic Modifier SETD8 as a Therapeutic Target for High-Grade Serous Ovarian Cancer.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "We investigate label-free measurement of molecular distribution by super-resolved Raman microscopy using surface plasmon (SP) localization. Localized SP was formed with plasmonic nanopost arrays (PNAs) for measurement of the molecular distribution in HeLa cells. Compared with conventional Raman microscopy on gold thin films, PNAs induce a localized near-field, which allows for the enhancement of the peak signal-to-noise ratio by as much as 4.5 dB in the Raman shifts. Super-resolved distributions of aromatic amino acids and lipids (C-C stretching and C-H2 twist mode) as targets in HeLa cells were obtained after image reconstruction. Results show almost 4-fold improvement on average in the lateral precision over conventional diffraction-limited Raman microscopy images. Combined with axial imaging in an evanescent field, the results suggest an improvement in optical resolution due to superlocalized light volume by more than an order of magnitude over that of conventional diffraction-limited Raman microscopy.", "classifications": [ { "id": "Fujita", "label": "Group Fujita", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Hongki", "last_name": "Lee", "name": null }, { "creator_type": "author", "first_name": "Kyungnam", "last_name": "Kang", "name": null }, { "creator_type": "author", "first_name": "Kentaro", "last_name": "Mochizuki", "name": null }, { "creator_type": "author", "first_name": "Changhun", "last_name": "Lee", "name": null }, { "creator_type": "author", "first_name": "Kar-Ann", "last_name": "Toh", "name": null }, { "creator_type": "author", "first_name": "Seung Ah", "last_name": "Lee", "name": null }, { "creator_type": "author", "first_name": "Katsumasa", "last_name": "Fujita", "name": null }, { "creator_type": "author", "first_name": "Donghyun", "last_name": "Kim", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/acs.nanolett.0c04219" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "33186047" } }, "mesh": [], "publication": { "conference_name": null, "date": "2020 Dec 9", "date_precision": "day", "issue": "12", "normalized_date": "2020-12-09", "pages": "8951-8958", "proceedings_title": null, "publisher": "", "title": "Nano letters", "volume": "20", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Surface Plasmon Localization-Based Super-resolved Raman Microscopy.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "(18)F-fluorodeoxyglucose ((18)F-FDG) positron emission tomography (PET)/computed tomography (CT) is usually used for staging or evaluation of treatment response rather than for cancer screening. However, (18)F-FDG PET/CT has also been used in Japan for cancer screening in people with no cancer symptoms, and accumulating evidence supports this application of (18)F-FDG PET/CT. Previously, we have observed a correlation between the saliva and tumor metabolomic profiles in patients with oral cancer. Hence, if salivary metabolites demonstrate a significant correlation with PET parameters such as the maximum standardized uptake value (SUV(max)), they may have the potential to be used as a screening tool before PET/CT to identify patients with high SUV(max). Hence, in this study, we aimed to explore the relationship between salivary metabolites and SUV(max) of (18)F-FDG PET/CT using previously collected data. (18)F-FDG PET/CT was performed for staging 26 patients with oral cancer. The collected data were integrated and analyzed along with quantified salivary hydrophilic metabolites obtained from the same patients with oral cancer and controls (n = 44). In total, 11 metabolites showed significant correlations with SUV(max) in the delayed phases. A multiple logistic regression model of the two metabolites showed the ability to discriminate between patients with oral cancer and controls, with an area under the receiver operating characteristic curve of 0.738 (p = 0.001). This study uniquely confirmed a relationship between salivary metabolites and SUV(max) of PET/CT in patients with oral cancer; salivary metabolites were significantly correlated with SUV(max). These salivary metabolites can be used as a screening tool before PET/CT to identify patients with high SUV(max), i.e., to detect the presence of oral cancer.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Shigeo", "last_name": "Ishikawa", "name": null }, { "creator_type": "author", "first_name": "Toshitada", "last_name": "Hiraka", "name": null }, { "creator_type": "author", "first_name": "Kazukuni", "last_name": "Kirii", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Sugimoto", "name": null }, { "creator_type": "author", "first_name": "Hiroaki", "last_name": "Shimamoto", "name": null }, { "creator_type": "author", "first_name": "Ayako", "last_name": "Sugano", "name": null }, { "creator_type": "author", "first_name": "Kenichiro", "last_name": "Kitabatake", "name": null }, { "creator_type": "author", "first_name": "Yuuki", "last_name": "Toyoguchi", "name": null }, { "creator_type": "author", "first_name": "Masafumi", "last_name": "Kanoto", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Nemoto", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Masaru", "last_name": "Tomita", "name": null }, { "creator_type": "author", "first_name": "Mitsuyoshi", "last_name": "Iino", "name": null } ], "identifiers": { "doi": { "normalized": "10.3390/jcm9123958" }, "pmcid": { "normalized": "PMC7762245" }, "pmid": { "normalized": "33297326" } }, "mesh": [], "publication": { "conference_name": null, "date": "2020 Dec 7", "date_precision": "day", "issue": "12", "normalized_date": "2020-12-07", "pages": "", "proceedings_title": null, "publisher": "", "title": "Journal of clinical medicine", "volume": "9", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Relationship between Standard Uptake Values of Positron Emission Tomography/Computed Tomography and Salivary Metabolites in Oral Cancer: A Pilot Study.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Cancer stem cells (CSCs) reside in a supportive niche, constituting a microenvironment comprised of adjacent stromal cells, vessels, and extracellular matrix. The ability of CSCs to participate in the development of endothelium constitutes an important characteristic that directly contributes to the general understanding of the mechanisms of tumorigenesis and tumor metastasis. The purpose of this work is to establish a reproducible methodology to investigate the tumor-initiation capability of ovarian cancer stem cells (OCSCs). Herein, we examined the neovascularization mechanism between endothelial cells and OCSCs along with the morphological changes of endothelial cells using the in vitro co-culture model NICO-1. This protocol allows visualization of the neovascularization step surrounding the OCSCs in a time course manner. The technique can provide insight regarding the angiogenetic properties of OCSCs in tumor metastasis.", "classifications": [ { "id": "Okamoto", "label": "Group Okamoto", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "contributor", "first_name": "Yuko", "last_name": "Miyagawa", "name": null }, { "creator_type": "contributor", "first_name": "Kazunori", "last_name": "Nagasaka", "name": null }, { "creator_type": "contributor", "first_name": "Kaoru", "last_name": "Yamawaki", "name": null }, { "creator_type": "contributor", "first_name": "Yutaro", "last_name": "Mori", "name": null }, { "creator_type": "contributor", "first_name": "Tatsuya", "last_name": "Ishiguro", "name": null }, { "creator_type": "contributor", "first_name": "Kei", "last_name": "Hashimoto", "name": null }, { "creator_type": "contributor", "first_name": "Ryoko", "last_name": "Koike", "name": null }, { "creator_type": "contributor", "first_name": "Siho", "last_name": "Fukui", "name": null }, { "creator_type": "contributor", "first_name": "Takeru", "last_name": "Sugihara", "name": null }, { "creator_type": "contributor", "first_name": "Takayuki", "last_name": "Ichinose", "name": null }, { "creator_type": "contributor", "first_name": "Haruko", "last_name": "Hiraike", "name": null }, { "creator_type": "contributor", "first_name": "Koichiro", "last_name": "Kido", "name": null }, { "creator_type": "contributor", "first_name": "Koji", "last_name": "Okamoto", "name": null }, { "creator_type": "contributor", "first_name": "Takayuki", "last_name": "Enomoto", "name": null }, { "creator_type": "contributor", "first_name": "Takuya", "last_name": "Ayabe", "name": null } ], "identifiers": { "doi": { "normalized": "10.3791/61751" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "33346189" } }, "mesh": [ { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Cell Transformation, Neoplastic", "descriptor_ui": "D002471", "major_topic": false }, { "descriptor": "Coculture Techniques", "descriptor_ui": "D018920", "major_topic": false }, { "descriptor": "Endothelial Cells", "descriptor_ui": "D042783", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Neoplastic Stem Cells", "descriptor_ui": "D014411", "major_topic": false }, { "descriptor": "Neovascularization, Pathologic", "descriptor_ui": "D009389", "major_topic": false }, { "descriptor": "Ovarian Neoplasms", "descriptor_ui": "D010051", "major_topic": false }, { "descriptor": "Tumor Microenvironment", "descriptor_ui": "D059016", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020 Dec 5", "date_precision": "day", "issue": "166", "normalized_date": "2020-12-05", "pages": "", "proceedings_title": null, "publisher": "", "title": "", "volume": "", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Evaluating the Angiogenetic Properties of Ovarian Cancer Stem-like Cells using the Three-dimensional Co-culture System, NICO-1.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Pattern-triggered immunity and effector-triggered immunity are two primary forms of innate immunity in land plants. The molecular components and connecting nodes of pattern-triggered immunity and effector-triggered immunity are not fully understood. Here, we report that the Arabidopsis calcium-dependent protein kinase CPK3 is a key regulator of both pattern-triggered immunity and effector-triggered immunity. In vitro and in vivo phosphorylation assays, coupled with genetic and cell biology-based analyses, show that actin-depolymerization factor 4 (ADF4) is a physiological substrate of CPK3, and that phosphorylation of ADF4 by CPK3 governs actin cytoskeletal organization associated with pattern-triggered immunity. CPK3 regulates stomatal closure induced by flg22 and is required for resistance to Pst DC3000. Our data further demonstrates that CPK3 is required for resistance to Pst DC3000 carrying the effector AvrPphB. These results suggest that CPK3 is a missing link between cytoskeleton organization, pattern-triggered immunity and effector-triggered immunity.", "classifications": [ { "id": "Higaki", "label": "Group Higaki", "parent": "Ueda", "type": "group" }, { "id": "Ueda", "label": "Team Ueda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yi-Ju", "last_name": "Lu", "name": null }, { "creator_type": "author", "first_name": "Pai", "last_name": "Li", "name": null }, { "creator_type": "author", "first_name": "Masaki", "last_name": "Shimono", "name": null }, { "creator_type": "author", "first_name": "Alex", "last_name": "Corrion", "name": null }, { "creator_type": "author", "first_name": "Takumi", "last_name": "Higaki", "name": null }, { "creator_type": "author", "first_name": "Sheng Yang", "last_name": "He", "name": null }, { "creator_type": "author", "first_name": "Brad", "last_name": "Day", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41467-020-20007-4" }, "pmcid": { "normalized": "PMC7718926" }, "pmid": { "normalized": "33277490" } }, "mesh": [ { "descriptor": "Actin Cytoskeleton", "descriptor_ui": "D008841", "major_topic": false }, { "descriptor": "Actin Depolymerizing Factors", "descriptor_ui": "D051339", "major_topic": false }, { "descriptor": "Amino Acid Sequence", "descriptor_ui": "D000595", "major_topic": false }, { "descriptor": "Arabidopsis", "descriptor_ui": "D017360", "major_topic": false }, { "descriptor": "Arabidopsis Proteins", "descriptor_ui": "D029681", "major_topic": false }, { "descriptor": "Calcium-Calmodulin-Dependent Protein Kinases", "descriptor_ui": "D017871", "major_topic": false }, { "descriptor": "Microscopy, Confocal", "descriptor_ui": "D018613", "major_topic": false }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": false }, { "descriptor": "Plant Diseases", "descriptor_ui": "D010935", "major_topic": false }, { "descriptor": "Plant Immunity", "descriptor_ui": "D057865", "major_topic": false }, { "descriptor": "Plants, Genetically Modified", "descriptor_ui": "D030821", "major_topic": false }, { "descriptor": "Pseudomonas syringae", "descriptor_ui": "D044224", "major_topic": false }, { "descriptor": "Sequence Homology, Amino Acid", "descriptor_ui": "D017386", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020 Dec 4", "date_precision": "day", "issue": "1", "normalized_date": "2020-12-04", "pages": "6234", "proceedings_title": null, "publisher": "", "title": "Nature communications", "volume": "11", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Arabidopsis calcium-dependent protein kinase 3 regulates actin cytoskeleton organization and immunity.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "A heterometallic one-dimensional (1-D) chain consisting of multiple kinds of metals, Rh, Pt, and Pd, with direct metal-metal bonds was successfully obtained by mixing a Rh dinuclear complex and Pt-Pd-Pt trinuclear complex. The Pt-Pd-Pt trinuclear complex can be reversibly one-electron-oxidized or -reduced, where the electron paramagnetic resonance spectrum of the one-electron-oxidized one shows an axially symmetric signal with hyperfine splitting by two Pt and Pd, indicating that an unpaired electron is delocalized to the d (z (2)) orbital of Pt-Pd-Pt. Utilized with the highest occupied molecular orbital and lowest unoccupied molecular orbital interaction at the d (z (2)) orbital, simple mixing of the Pt-Pd-Pt trinuclear complex and Rh dinuclear complex in adequate solvents afforded heterometallic 1-D chains, which are aligned as -Rh-Rh-Pt-Pd-Pt-. Several physical measurements revealed that the metal oxidation state is +2. Diffuse reflectance spectra and theoretical calculations show that heterometallic 1-D chains have sigma-type conduction and valence bands where pi*(Rh(2)) are lying between them, whose gaps become narrower than the prototype chains aligned as -Rh-Rh-Pt-Pt-Pt-Pt-. The narrower band gaps are induced by destabilization of the sigma-type valence bands and accompanied by insertion of Pd ions because the d-orbital energy level of Pd is closer in value to Rh compared with Pt. Flash-photolysis time-resolved microwave conductivity measurements exhibited an increase in the product of charge carrier mobility and its generation efficiency (8.1 x 10(-5) to 4.6 x 10(-4) cm(2) V(-1) s(-1)) with narrowing the band gaps, suggesting that the better conductivity is attributed to shorter metal-metal distances in 1-D chains. These results imply the possibilities of controlling band gap with ligand modification and third metal insertion in heterometallic 1-D chains to show various conductivities.", "classifications": [ { "id": "Hijikata", "label": "Group Hijikata", "parent": "Tsuchiya", "type": "group" }, { "id": "Tsuchiya", "label": "Team Tsuchiya", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Kazuhiro", "last_name": "Uemura", "name": null }, { "creator_type": "author", "first_name": "Daiki", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Jenny", "last_name": "Pirillo", "name": null }, { "creator_type": "author", "first_name": "Yuh", "last_name": "Hijikata", "name": null }, { "creator_type": "author", "first_name": "Akinori", "last_name": "Saeki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/acsomega.0c04317" }, "pmcid": { "normalized": "PMC7711699" }, "pmid": { "normalized": "33283099" } }, "mesh": [], "publication": { "conference_name": null, "date": "2020 Dec 1", "date_precision": "day", "issue": "47", "normalized_date": "2020-12-01", "pages": "30502-30518", "proceedings_title": null, "publisher": "", "title": "ACS omega", "volume": "5", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Modulation of Band Gaps toward Varying Conductivities in Heterometallic One-Dimensional Chains by Ligand Alteration and Third Metal Insertion.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Impaired glucose tolerance associated with obesity causes postprandial hyperglycemia and can lead to type 2 diabetes. To study the differences in liver metabolism in healthy and obese states, we constructed and analyzed transomics glucose-responsive metabolic networks with layers for metabolites, expression data for metabolic enzyme genes, transcription factors, and insulin signaling proteins from the livers of healthy and obese mice. We integrated multiomics time course data from wild-type and leptin-deficient obese (ob/ob) mice after orally administered glucose. In wild-type mice, metabolic reactions were rapidly regulated within 10 min of oral glucose administration by glucose-responsive metabolites, which functioned as allosteric regulators and substrates of metabolic enzymes, and by Akt-induced changes in the expression of glucose-responsive genes encoding metabolic enzymes. In ob/ob mice, the majority of rapid regulation by glucose-responsive metabolites was absent. Instead, glucose administration produced slow changes in the expression of carbohydrate, lipid, and amino acid metabolic enzyme-encoding genes to alter metabolic reactions on a time scale of hours. Few regulatory events occurred in both healthy and obese mice. Thus, our transomics network analysis revealed that regulation of glucose-responsive liver metabolism is mediated through different mechanisms in healthy and obese states. Rapid changes in allosteric regulators and substrates and in gene expression dominate the healthy state, whereas slow changes in gene expression dominate the obese state.", "classifications": [ { "id": "Kuroda", "label": "Group Kuroda", "parent": "Kuroda", "type": "group" }, { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Toshiya", "last_name": "Kokaji", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Hatano", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Katsuyuki", "last_name": "Yugi", "name": null }, { "creator_type": "author", "first_name": "Miki", "last_name": "Eto", "name": null }, { "creator_type": "author", "first_name": "Keigo", "last_name": "Morita", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Ohno", "name": null }, { "creator_type": "author", "first_name": "Masashi", "last_name": "Fujii", "name": null }, { "creator_type": "author", "first_name": "Ken-Ichi", "last_name": "Hironaka", "name": null }, { "creator_type": "author", "first_name": "Riku", "last_name": "Egami", "name": null }, { "creator_type": "author", "first_name": "Akira", "last_name": "Terakawa", "name": null }, { "creator_type": "author", "first_name": "Takaho", "last_name": "Tsuchiya", "name": null }, { "creator_type": "author", "first_name": "Haruka", "last_name": "Ozaki", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Inoue", "name": null }, { "creator_type": "author", "first_name": "Shinsuke", "last_name": "Uda", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Kubota", "name": null }, { "creator_type": "author", "first_name": "Yutaka", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Kazutaka", "last_name": "Ikeda", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Arita", "name": null }, { "creator_type": "author", "first_name": "Masaki", "last_name": "Matsumoto", "name": null }, { "creator_type": "author", "first_name": "Keiichi I.", "last_name": "Nakayama", "name": null }, { "creator_type": "author", "first_name": "Akiyoshi", "last_name": "Hirayama", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Kuroda", "name": null } ], "identifiers": { "doi": { "normalized": "10.1126/scisignal.aaz1236" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "33262292" } }, "mesh": [ { "descriptor": "Allosteric Regulation", "descriptor_ui": "D000494", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Disease Models, Animal", "descriptor_ui": "D004195", "major_topic": false }, { "descriptor": "Gene Expression Profiling", "descriptor_ui": "D020869", "major_topic": true }, { "descriptor": "Gene Expression Regulation", "descriptor_ui": "D005786", "major_topic": true }, { "descriptor": "Glucose", "descriptor_ui": "D005947", "major_topic": false }, { "descriptor": "Liver", "descriptor_ui": "D008099", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Obese", "descriptor_ui": "D008820", "major_topic": false }, { "descriptor": "Obesity", "descriptor_ui": "D009765", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": true } ], "publication": { "conference_name": null, "date": "2020 Dec 1", "date_precision": "day", "issue": "660", "normalized_date": "2020-12-01", "pages": "eaaz1236", "proceedings_title": null, "publisher": "", "title": "Science signaling", "volume": "13", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Transomics analysis reveals allosteric and gene regulation axes for altered hepatic glucose-responsive metabolism in obesity.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Significance: Redox biology is gaining ground in research related to human physiology (metabolism, signaling), pathophysiology (cancer, cardiovascular disease, neurodegeneration), and toxicology (radiation- or xenobiotic-induced damage). A major hurdle in advancing redox medicine is the current lack of understanding the mechanisms underpinning the observed detrimental or beneficial in vivo effects. To gain deeper insights into the underlying molecular pathways of redox regulation, we need to appreciate the strengths and limitations of the currently available methods. Recent Advances: Reactive sulfur species (RSS), including cysteine derivatives of peptides and proteins along with small molecules such as hydrogen sulfide or inorganic polysulfides, are major players in redox biology. RSS-mediated regulation of protein functions is a widely studied mechanism in the field, and considerable efforts have been devoted to the development of selective detection methods. Critical Issues: A large number of available methods rely on an alkylation step to freeze the dynamism of consecutive oxidation and reduction events among RSS at a particular time point inside the cell. This process uses the assumption that alkylation blocks all redox events instantaneously. We argue that unfortunately this is often not the case, which could have serious impacts on detected sulfur species speciation and confound experimental results. Future Directions: Novel technologies and prudent optimization of existing methods to accurately characterize the dynamic redox status of the thiol proteome as well as detailed understanding of regulatory and signaling capacities of protein polysulfidation are crucial to open new routes toward therapeutic interventions.", "classifications": [ { "id": "Akaike", "label": "Group Akaike", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Peter", "last_name": "Nagy", "name": null }, { "creator_type": "author", "first_name": "Eva", "last_name": "Doka", "name": null }, { "creator_type": "author", "first_name": "Tomoaki", "last_name": "Ida", "name": null }, { "creator_type": "author", "first_name": "Takaaki", "last_name": "Akaike", "name": null } ], "identifiers": { "doi": { "normalized": "10.1089/ars.2020.8077" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "32631072" } }, "mesh": [ { "descriptor": "Alkylation", "descriptor_ui": "D000478", "major_topic": false }, { "descriptor": "Cysteine", "descriptor_ui": "D003545", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Hydrogen Sulfide", "descriptor_ui": "D006862", "major_topic": false }, { "descriptor": "Metabolic Networks and Pathways", "descriptor_ui": "D053858", "major_topic": false }, { "descriptor": "Oxidation-Reduction", "descriptor_ui": "D010084", "major_topic": true }, { "descriptor": "Reactive Oxygen Species", "descriptor_ui": "D017382", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Sulfhydryl Compounds", "descriptor_ui": "D013438", "major_topic": false }, { "descriptor": "Sulfur", "descriptor_ui": "D013455", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020 Dec 1", "date_precision": "day", "issue": "16", "normalized_date": "2020-12-01", "pages": "1174-1189", "proceedings_title": null, "publisher": "", "title": "Antioxidants & redox signaling", "volume": "33", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Measuring Reactive Sulfur Species and Thiol Oxidation States: Challenges and Cautions in Relation to Alkylation-Based Protocols.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "In recent years, advances in artificial intelligence (AI) technology have led to the rapid clinical implementation of devices with AI technology in the medical field. More than 60 AI-equipped medical devices have already been approved by the Food and Drug Administration (FDA) in the United States, and the active introduction of AI technology is considered to be an inevitable trend in the future of medicine. In the field of oncology, clinical applications of medical devices using AI technology are already underway, mainly in radiology, and AI technology is expected to be positioned as an important core technology. In particular, \"precision medicine,\" a medical treatment that selects the most appropriate treatment for each patient based on a vast amount of medical data such as genome information, has become a worldwide trend; AI technology is expected to be utilized in the process of extracting truly useful information from a large amount of medical data and applying it to diagnosis and treatment. In this review, we would like to introduce the history of AI technology and the current state of medical AI, especially in the oncology field, as well as discuss the possibilities and challenges of AI technology in the medical field.", "classifications": [ { "id": "Hamamoto", "label": "Group Hamamoto", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Ryuji", "last_name": "Hamamoto", "name": null }, { "creator_type": "author", "first_name": "Kruthi", "last_name": "Suvarna", "name": null }, { "creator_type": "author", "first_name": "Masayoshi", "last_name": "Yamada", "name": null }, { "creator_type": "author", "first_name": "Kazuma", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Norio", "last_name": "Shinkai", "name": null }, { "creator_type": "author", "first_name": "Mototaka", "last_name": "Miyake", "name": null }, { "creator_type": "author", "first_name": "Masamichi", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Shunichi", "last_name": "Jinnai", "name": null }, { "creator_type": "author", "first_name": "Ryo", "last_name": "Shimoyama", "name": null }, { "creator_type": "author", "first_name": "Akira", "last_name": "Sakai", "name": null }, { "creator_type": "author", "first_name": "Ken", "last_name": "Takasawa", "name": null }, { "creator_type": "author", "first_name": "Amina", "last_name": "Bolatkan", "name": null }, { "creator_type": "author", "first_name": "Kanto", "last_name": "Shozu", "name": null }, { "creator_type": "author", "first_name": "Ai", "last_name": "Dozen", "name": null }, { "creator_type": "author", "first_name": "Hidenori", "last_name": "Machino", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Ken", "last_name": "Asada", "name": null }, { "creator_type": "author", "first_name": "Masaaki", "last_name": "Komatsu", "name": null }, { "creator_type": "author", "first_name": "Jun", "last_name": "Sese", "name": null }, { "creator_type": "author", "first_name": "Syuzo", "last_name": "Kaneko", "name": null } ], "identifiers": { "doi": { "normalized": "10.3390/cancers12123532" }, "pmcid": { "normalized": "PMC7760590" }, "pmid": { "normalized": "33256107" } }, "mesh": [], "publication": { "conference_name": null, "date": "2020 Nov 26", "date_precision": "day", "issue": "12", "normalized_date": "2020-11-26", "pages": "", "proceedings_title": null, "publisher": "", "title": "Cancers", "volume": "12", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Application of Artificial Intelligence Technology in Oncology: Towards the Establishment of Precision Medicine.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Visualizing live-cell uptake of small-molecule drugs is paramount for drug development and pharmaceutical sciences. Bioorthogonal imaging with click chemistry has made significant contributions to the field, visualizing small molecules in cells. Furthermore, recent developments in Raman microscopy, including stimulated Raman scattering (SRS) microscopy, have realized direct visualization of alkyne-tagged small-molecule drugs in live cells. However, Raman and SRS microscopy still suffer from limited detection sensitivity with low concentration molecules for observing temporal dynamics of drug uptake. Here, we demonstrate the combination of alkyne-tag and surface-enhanced Raman scattering (SERS) microscopy for the real-time monitoring of drug uptake in live cells. Gold nanoparticles are introduced into lysosomes of live cells by endocytosis and work as SERS probes. Raman signals of alkynes can be boosted by enhanced electric fields generated by plasmon resonance of gold nanoparticles when alkyne-tagged small molecules are colocalized with the nanoparticles. With time-lapse 3D SERS imaging, this technique allows us to investigate drug uptake by live cells with different chemical and physical conditions. We also perform quantitative evaluation of the uptake speed at the single-cell level using digital SERS counting under different quantities of drug molecules and temperature conditions. Our results illustrate that alkyne-tag SERS microscopy has a potential to be an alternative bioorthogonal imaging technique to investigate temporal dynamics of small-molecule uptake of live cells for pharmaceutical research.", "classifications": [ { "id": "Fujita", "label": "Group Fujita", "parent": "Fujita", "type": "group" }, { "id": "Sodeoka", "label": "Group Sodeoka", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Kota", "last_name": "Koike", "name": null }, { "creator_type": "author", "first_name": "Kazuki", "last_name": "Bando", "name": null }, { "creator_type": "author", "first_name": "Jun", "last_name": "Ando", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Yamakoshi", "name": null }, { "creator_type": "author", "first_name": "Naoki", "last_name": "Terayama", "name": null }, { "creator_type": "author", "first_name": "Kosuke", "last_name": "Dodo", "name": null }, { "creator_type": "author", "first_name": "Nicholas Isaac", "last_name": "Smith", "name": null }, { "creator_type": "author", "first_name": "Mikiko", "last_name": "Sodeoka", "name": null }, { "creator_type": "author", "first_name": "Katsumasa", "last_name": "Fujita", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/acsnano.0c05010" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "33079538" } }, "mesh": [ { "descriptor": "Alkynes", "descriptor_ui": "D000480", "major_topic": false }, { "descriptor": "Gold", "descriptor_ui": "D006046", "major_topic": false }, { "descriptor": "Metal Nanoparticles", "descriptor_ui": "D053768", "major_topic": true }, { "descriptor": "Microscopy", "descriptor_ui": "D008853", "major_topic": true }, { "descriptor": "Pharmaceutical Preparations", "descriptor_ui": "D004364", "major_topic": true }, { "descriptor": "Spectrum Analysis, Raman", "descriptor_ui": "D013059", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020 Nov 24", "date_precision": "day", "issue": "11", "normalized_date": "2020-11-24", "pages": "15032-15041", "proceedings_title": null, "publisher": "", "title": "ACS nano", "volume": "14", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Quantitative Drug Dynamics Visualized by Alkyne-Tagged Plasmonic-Enhanced Raman Microscopy.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: Previous studies have demonstrated that individuals with autism spectrum disorder (ASD) exhibit dysfunction in the three attention systems (i.e., alerting, orienting, and executive control) as well as atypical relationships among these systems. Additionally, other studies have reported that individuals with subclinical but high levels of autistic traits show similar attentional tendencies to those observed in ASD. Based on these findings, it was hypothesized that autistic traits would affect the functions and relationships of the three attention systems in a general population. Resting-state functional magnetic resonance imaging (fMRI) was performed in 119 healthy adults to investigate relationships between autistic traits and within- and between-system functional connectivity (FC) among the three attention systems. Twenty-six regions of interest that were defined as components of the three attention systems by a previous task-based fMRI study were examined in terms of within- and between-system FC. We assessed autistic traits using the Autism-Spectrum Quotient. RESULTS: Correlational analyses revealed that autistic traits were significantly correlated with between-system FC, but not with within-system FC. CONCLUSIONS: Our results imply that a high autistic trait level, even when subclinical, is associated with the way the three attention systems interact.", "classifications": [ { "id": "Fujiwara", "label": "Group Fujiwara", "parent": "Fujiwara", "type": "group" }, { "id": "Fujiwara", "label": "Team Fujiwara", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Sayaka", "last_name": "Yoshimura", "name": null }, { "creator_type": "author", "first_name": "Kei", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Tsukasa", "last_name": "Ueno", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Miyagi", "name": null }, { "creator_type": "author", "first_name": "Naoya", "last_name": "Oishi", "name": null }, { "creator_type": "author", "first_name": "Toshiya", "last_name": "Murai", "name": null }, { "creator_type": "author", "first_name": "Hironobu", "last_name": "Fujiwara", "name": null } ], "identifiers": { "doi": { "normalized": "10.1186/s12868-020-00603-2" }, "pmcid": { "normalized": "PMC7686764" }, "pmid": { "normalized": "33228525" } }, "mesh": [ { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Attention", "descriptor_ui": "D001288", "major_topic": true }, { "descriptor": "Autism Spectrum Disorder", "descriptor_ui": "D000067877", "major_topic": false }, { "descriptor": "Brain Mapping", "descriptor_ui": "D001931", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Image Processing, Computer-Assisted", "descriptor_ui": "D007091", "major_topic": false }, { "descriptor": "Magnetic Resonance Imaging", "descriptor_ui": "D008279", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Nerve Net", "descriptor_ui": "D009415", "major_topic": false }, { "descriptor": "Neural Pathways", "descriptor_ui": "D009434", "major_topic": false }, { "descriptor": "Neuropsychological Tests", "descriptor_ui": "D009483", "major_topic": false }, { "descriptor": "Young Adult", "descriptor_ui": "D055815", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020 Nov 23", "date_precision": "day", "issue": "1", "normalized_date": "2020-11-23", "pages": "49", "proceedings_title": null, "publisher": "", "title": "BMC neuroscience", "volume": "21", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Autistic traits are associated with the functional connectivity of between-but not within-attention systems in the general population.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Bacterial photoactivated adenylyl cyclase (bPAC) has been widely used in signal transduction research. However, due to its low two-photon absorption, bPAC cannot be efficiently activated by two-photon (2P) excitation. Taking advantage of the high two-photon absorption of monomeric teal fluorescent protein 1 (mTFP1), we herein developed 2P-activatable bPAC (2pabPAC), a fusion protein consisting of bPAC and mTFP1. In 2pabPAC, the energy absorbed by mTFP1 excites bPAC by Furster resonance energy transfer (FRET) at ca. 43% efficiency. The light-induced increase in cAMP was monitored by a red-shifted FRET biosensor for PKA. In 3D MDCK cells and mouse liver, PKA was activated at single-cell resolution under a 2P microscope. We found that PKA activation in a single hepatocyte caused PKA activation in neighboring cells, indicating the propagation of PKA activation. Thus, 2pabPAC will provide a versatile platform for controlling the cAMP signaling pathway and investigating cell-to-cell communication in vivo.", "classifications": [], "creators": [ { "creator_type": "author", "first_name": "Tomoaki", "last_name": "Kinjo", "name": null }, { "creator_type": "author", "first_name": "Tetsuya", "last_name": "Watabe", "name": null }, { "creator_type": "author", "first_name": "Kenju", "last_name": "Kobachi", "name": null }, { "creator_type": "author", "first_name": "Kenta", "last_name": "Terai", "name": null }, { "creator_type": "author", "first_name": "Michiyuki", "last_name": "Matsuda", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/acschembio.0c00333" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "33074647" } }, "mesh": [ { "descriptor": "Adenylyl Cyclases", "descriptor_ui": "D000262", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Bacteria", "descriptor_ui": "D001419", "major_topic": false }, { "descriptor": "Biosensing Techniques", "descriptor_ui": "D015374", "major_topic": false }, { "descriptor": "Cell Communication", "descriptor_ui": "D002450", "major_topic": false }, { "descriptor": "Cyclic AMP", "descriptor_ui": "D000242", "major_topic": false }, { "descriptor": "Cyclic AMP-Dependent Protein Kinases", "descriptor_ui": "D017868", "major_topic": false }, { "descriptor": "Dogs", "descriptor_ui": "D004285", "major_topic": false }, { "descriptor": "Enzyme Activation", "descriptor_ui": "D004789", "major_topic": false }, { "descriptor": "Fluorescence Resonance Energy Transfer", "descriptor_ui": "D031541", "major_topic": false }, { "descriptor": "Fluorescent Dyes", "descriptor_ui": "D005456", "major_topic": false }, { "descriptor": "Green Fluorescent Proteins", "descriptor_ui": "D049452", "major_topic": false }, { "descriptor": "HeLa Cells", "descriptor_ui": "D006367", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Liver", "descriptor_ui": "D008099", "major_topic": false }, { "descriptor": "Madin Darby Canine Kidney Cells", "descriptor_ui": "D061985", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": true }, { "descriptor": "Single-Cell Analysis", "descriptor_ui": "D059010", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020 Nov 20", "date_precision": "day", "issue": "11", "normalized_date": "2020-11-20", "pages": "2848-2853", "proceedings_title": null, "publisher": "", "title": "ACS chemical biology", "volume": "15", "year": 2020 }, "ssbd": { "database": [ "ssbd-database-000177" ], "repository": [ "ssbd-repos-000177" ] }, "title": "Single-Cell Activation of the cAMP-Signaling Pathway in 3D Tissues with FRET-Assisted Two-Photon Activation of bPAC.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The nuclear lamina plays an important role in the regulation of chromatin organization and gene positioning in animals. CROWDED NUCLEI (CRWN) is a strong candidate for the plant nuclear lamina protein in Arabidopsis thaliana but its biological function was largely unknown. Here, we show that CRWNs localize at the nuclear lamina and build the meshwork structure. Fluorescence in situ hybridization and RNA-seq analyses revealed that CRWNs regulate chromatin distribution and gene expression. More than 2000 differentially expressed genes were identified in the crwn1crwn4 double mutant. Copper-associated (CA) genes that form a gene cluster on chromosome 5 were among the downregulated genes in the double mutant exhibiting low tolerance to excess copper. Our analyses showed this low tolerance to copper was associated with the suppression of CA gene expression and that CRWN1 interacts with the CA gene locus, enabling the locus to localize at the nuclear lamina under excess copper conditions.", "classifications": [ { "id": "Sato", "label": "Group Sato", "parent": "Tsuchiya", "type": "group" }, { "id": "Tsuchiya", "label": "Team Tsuchiya", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yuki", "last_name": "Sakamoto", "name": null }, { "creator_type": "author", "first_name": "Mayuko", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Yoshikatsu", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Akihito", "last_name": "Harada", "name": null }, { "creator_type": "author", "first_name": "Takamasa", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Chieko", "last_name": "Goto", "name": null }, { "creator_type": "author", "first_name": "Kentaro", "last_name": "Tamura", "name": null }, { "creator_type": "author", "first_name": "Kiminori", "last_name": "Toyooka", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Kimura", "name": null }, { "creator_type": "author", "first_name": "Yasuyuki", "last_name": "Ohkawa", "name": null }, { "creator_type": "author", "first_name": "Ikuko", "last_name": "Hara-Nishimura", "name": null }, { "creator_type": "author", "first_name": "Shingo", "last_name": "Takagi", "name": null }, { "creator_type": "author", "first_name": "Sachihiro", "last_name": "Matsunaga", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41467-020-19621-z" }, "pmcid": { "normalized": "PMC7679404" }, "pmid": { "normalized": "33219233" } }, "mesh": [ { "descriptor": "Arabidopsis", "descriptor_ui": "D017360", "major_topic": false }, { "descriptor": "Arabidopsis Proteins", "descriptor_ui": "D029681", "major_topic": true }, { "descriptor": "Cell Nucleus", "descriptor_ui": "D002467", "major_topic": false }, { "descriptor": "Chromatin", "descriptor_ui": "D002843", "major_topic": false }, { "descriptor": "Copper", "descriptor_ui": "D003300", "major_topic": false }, { "descriptor": "Gene Expression Regulation, Plant", "descriptor_ui": "D018506", "major_topic": false }, { "descriptor": "In Situ Hybridization, Fluorescence", "descriptor_ui": "D017404", "major_topic": false }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": false }, { "descriptor": "Nuclear Lamina", "descriptor_ui": "D034881", "major_topic": true }, { "descriptor": "Nuclear Proteins", "descriptor_ui": "D009687", "major_topic": true }, { "descriptor": "Plant Proteins", "descriptor_ui": "D010940", "major_topic": false }, { "descriptor": "RNA-Seq", "descriptor_ui": "D000081246", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020 Nov 20", "date_precision": "day", "issue": "1", "normalized_date": "2020-11-20", "pages": "5914", "proceedings_title": null, "publisher": "", "title": "Nature communications", "volume": "11", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Subnuclear gene positioning through lamina association affects copper tolerance.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "We designed and synthesized a series of derivatives containing the right-side DFGH-ring structure of physalin-type natural products, decorated with a hydrophobic substituent. The synthetic scheme utilizes a highly efficient, one-pot protocol for simultaneous construction of the GH-ring system, promoted by HF/pyridine. Among the compounds synthesized, 5d inhibited TNF-alpha-stimulated NF-kappaB activation with similar potency to physalin B.", "classifications": [ { "id": "Sodeoka", "label": "Group Sodeoka", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Makoto", "last_name": "Yoritate", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Morita", "name": null }, { "creator_type": "author", "first_name": "Manuel", "last_name": "Gemander", "name": null }, { "creator_type": "author", "first_name": "Masaki", "last_name": "Morita", "name": null }, { "creator_type": "author", "first_name": "Tomohiro", "last_name": "Yamashita", "name": null }, { "creator_type": "author", "first_name": "Mikiko", "last_name": "Sodeoka", "name": null }, { "creator_type": "author", "first_name": "Go", "last_name": "Hirai", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/acs.orglett.0c03255" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "33124828" } }, "mesh": [ { "descriptor": "Molecular Structure", "descriptor_ui": "D015394", "major_topic": false }, { "descriptor": "NF-kappa B", "descriptor_ui": "D016328", "major_topic": false }, { "descriptor": "Secosteroids", "descriptor_ui": "D012632", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Structure-Activity Relationship", "descriptor_ui": "D013329", "major_topic": false }, { "descriptor": "Tumor Necrosis Factor-alpha", "descriptor_ui": "D014409", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020 Nov 20", "date_precision": "day", "issue": "22", "normalized_date": "2020-11-20", "pages": "8877-8881", "proceedings_title": null, "publisher": "", "title": "Organic letters", "volume": "22", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Synthesis of DFGH-Ring Derivatives of Physalins via One-Pot Construction of GH-Ring and Evaluation of Their NF-kappaB-Inhibitory Activity.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "To date, various human disease models in small fish-such as medaka (Oryzias lapties)-have been developed for medical and pharmacological studies. Although genetic and environmental homogeneities exist, disease progressions can show large individual differences in animal models. In this study, we established an intact in vivo angiographic approach and explored vascular networks in the telencephalon of wild-type adult medaka using the spectral-domain optical coherence tomography. Our approach, which required neither surgical operations nor labeling agents, allowed to visualize blood vessels in medaka telencephala as small as about 8 µm, that is, almost the size of the blood cells of medaka. Besides, we could show the three-dimensional microvascular distribution in the medaka telencephalon. Therefore, the intact in vivo imaging via optical coherence tomography can be used to perform follow-up studies on cerebrovascular alterations in metabolic syndrome and their associations with neurodegenerative disease models in medaka.", "classifications": [ { "id": "Suzuki", "label": "Group Suzuki", "parent": "Takekawa", "type": "group" }, { "id": "Takekawa", "label": "Team Takekawa", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Takashi", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Tomohiro", "last_name": "Ueno", "name": null }, { "creator_type": "author", "first_name": "Naoya", "last_name": "Oishi", "name": null }, { "creator_type": "author", "first_name": "Hidenao", "last_name": "Fukuyama", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41598-020-76468-6" }, "pmcid": { "normalized": "PMC7669881" }, "pmid": { "normalized": "33199719" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cerebral Angiography", "descriptor_ui": "D002533", "major_topic": false }, { "descriptor": "Computed Tomography Angiography", "descriptor_ui": "D000072226", "major_topic": false }, { "descriptor": "Microvessels", "descriptor_ui": "D055806", "major_topic": false }, { "descriptor": "Models, Animal", "descriptor_ui": "D023421", "major_topic": false }, { "descriptor": "Oryzias", "descriptor_ui": "D009990", "major_topic": false }, { "descriptor": "Telencephalon", "descriptor_ui": "D013687", "major_topic": false }, { "descriptor": "Tomography, Optical Coherence", "descriptor_ui": "D041623", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020 Nov 16", "date_precision": "day", "issue": "1", "normalized_date": "2020-11-16", "pages": "19831", "proceedings_title": null, "publisher": "", "title": "Scientific reports", "volume": "10", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Intact in vivo visualization of telencephalic microvasculature in medaka using optical coherence tomography.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Osteomodulin (OMD) and proline/arginine-rich end leucine repeat protein (PRELP) are secreted extracellular matrix proteins belonging to the small leucine-rich proteoglycans family. We found that OMD and PRELP were specifically expressed in umbrella cells in bladder epithelia, and their expression levels were dramatically downregulated in all bladder cancers from very early stages and various epithelial cancers. Our in vitro studies including gene expression profiling using bladder cancer cell lines revealed that OMD or PRELP application suppressed the cancer progression by inhibiting TGF-beta and EGF pathways, which reversed epithelial-mesenchymal transition (EMT), activated cell-cell adhesion, and inhibited various oncogenic pathways. Furthermore, the overexpression of OMD in bladder cancer cells strongly inhibited the anchorage-independent growth and tumorigenicity in mouse xenograft studies. On the other hand, we found that in the bladder epithelia, the knockout mice of OMD and/or PRELP gene caused partial EMT and a loss of tight junctions of the umbrella cells and resulted in formation of a bladder carcinoma in situ-like structure by spontaneous breakdowns of the umbrella cell layer. Furthermore, the ontological analysis of the expression profiling of an OMD knockout mouse bladder demonstrated very high similarity with those obtained from human bladder cancers. Our data indicate that OMD and PRELP are endogenous inhibitors of cancer initiation and progression by controlling EMT. OMD and/or PRELP may have potential for the treatment of bladder cancer.", "classifications": [ { "id": "Hamamoto", "label": "Group Hamamoto", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Vasiliki", "last_name": "Papadaki", "name": null }, { "creator_type": "author", "first_name": "Ken", "last_name": "Asada", "name": null }, { "creator_type": "author", "first_name": "Julie K.", "last_name": "Watson", "name": null }, { "creator_type": "author", "first_name": "Toshiya", "last_name": "Tamura", "name": null }, { "creator_type": "author", "first_name": "Alex", "last_name": "Leung", "name": null }, { "creator_type": "author", "first_name": "Jack", "last_name": "Hopkins", "name": null }, { "creator_type": "author", "first_name": "Margaret", "last_name": "Dellett", "name": null }, { "creator_type": "author", "first_name": "Noriaki", "last_name": "Sasai", "name": null }, { "creator_type": "author", "first_name": "Hongorzul", "last_name": "Davaapil", "name": null }, { "creator_type": "author", "first_name": "Serena", "last_name": "Nik-Zainal", "name": null }, { "creator_type": "author", "first_name": "Rebecca", "last_name": "Longbottom", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Nakakido", "name": null }, { "creator_type": "author", "first_name": "Ryo", "last_name": "Torii", "name": null }, { "creator_type": "author", "first_name": "Abhi", "last_name": "Veerakumarasivam", "name": null }, { "creator_type": "author", "first_name": "Syuzo", "last_name": "Kaneko", "name": null }, { "creator_type": "author", "first_name": "Mandeep S.", "last_name": "Sagoo", "name": null }, { "creator_type": "author", "first_name": "Gillian", "last_name": "Murphy", "name": null }, { "creator_type": "author", "first_name": "Akihisa", "last_name": "Mitani", "name": null }, { "creator_type": "author", "first_name": "Kohei", "last_name": "Tsumoto", "name": null }, { "creator_type": "author", "first_name": "John D.", "last_name": "Kelly", "name": null }, { "creator_type": "author", "first_name": "Ryuji", "last_name": "Hamamoto", "name": null }, { "creator_type": "author", "first_name": "Shin-Ichi", "last_name": "Ohnuma", "name": null } ], "identifiers": { "doi": { "normalized": "10.3390/cancers12113362" }, "pmcid": { "normalized": "PMC7697838" }, "pmid": { "normalized": "33202923" } }, "mesh": [], "publication": { "conference_name": null, "date": "2020 Nov 13", "date_precision": "day", "issue": "11", "normalized_date": "2020-11-13", "pages": "", "proceedings_title": null, "publisher": "", "title": "Cancers", "volume": "12", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Two Secreted Proteoglycans, Activators of Urothelial Cell-Cell Adhesion, Negatively Contribute to Bladder Cancer Initiation and Progression.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Guanosine 3',5'-bis(pyrophosphate) (ppGpp) functions as a second messenger in bacteria to adjust their physiology in response to environmental changes. In recent years, the ppGpp-specific hydrolase, metazoan SpoT homolog-1 (Mesh1), was shown to have important roles for growth under nutrient deficiency in Drosophila melanogaster. Curiously, however, ppGpp has never been detected in animal cells, and therefore the physiological relevance of this molecule, if any, in metazoans has not been established. Here, we report the detection of ppGpp in Drosophila and human cells and demonstrate that ppGpp accumulation induces metabolic changes, cell death, and eventually lethality in Drosophila. Our results provide the evidence of the existence and function of the ppGpp-dependent stringent response in animals.", "classifications": [ { "id": "Suzuki", "label": "Group Suzuki", "parent": "Takekawa", "type": "group" }, { "id": "Takekawa", "label": "Team Takekawa", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Doshun", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Hinata", "last_name": "Kawamura", "name": null }, { "creator_type": "author", "first_name": "Akira", "last_name": "Oikawa", "name": null }, { "creator_type": "author", "first_name": "Yuta", "last_name": "Ihara", "name": null }, { "creator_type": "author", "first_name": "Toshio", "last_name": "Shibata", "name": null }, { "creator_type": "author", "first_name": "Nobuhiro", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Tsunaki", "last_name": "Asano", "name": null }, { "creator_type": "author", "first_name": "Shun-Ichiro", "last_name": "Kawabata", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Shinji", "last_name": "Masuda", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s42003-020-01368-4" }, "pmcid": { "normalized": "PMC7666150" }, "pmid": { "normalized": "33188280" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Bacteria", "descriptor_ui": "D001419", "major_topic": false }, { "descriptor": "Drosophila melanogaster", "descriptor_ui": "D004331", "major_topic": false }, { "descriptor": "Guanosine Pentaphosphate", "descriptor_ui": "D006158", "major_topic": false }, { "descriptor": "Guanosine Tetraphosphate", "descriptor_ui": "D006159", "major_topic": true }, { "descriptor": "Pyrophosphatases", "descriptor_ui": "D011755", "major_topic": false }, { "descriptor": "Second Messenger Systems", "descriptor_ui": "D015290", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020 Nov 13", "date_precision": "day", "issue": "1", "normalized_date": "2020-11-13", "pages": "671", "proceedings_title": null, "publisher": "", "title": "Communications biology", "volume": "3", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "ppGpp functions as an alarmone in metazoa.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Dysbiosis of the gut microbiota affects physiological processes, including brain functions, by altering the intestinal metabolism. Here we examined the effects of the gut microbiota on sleep/wake regulation. C57BL/6 male mice were treated with broad-spectrum antibiotics for 4 weeks to deplete their gut microbiota. Metabolome profiling of cecal contents in antibiotic-induced microbiota-depleted (AIMD) and control mice showed significant variations in the metabolism of amino acids and vitamins related to neurotransmission, including depletion of serotonin and vitamin B6, in the AIMD mice. Sleep analysis based on electroencephalogram and electromyogram recordings revealed that AIMD mice spent significantly less time in non-rapid eye movement sleep (NREMS) during the light phase while spending more time in NREMS and rapid eye movement sleep (REMS) during the dark phase. The number of REMS episodes seen in AIMD mice increased during both light and dark phases, and this was accompanied by frequent transitions from NREMS to REMS. In addition, the theta power density during REMS was lower in AIMD mice during the light phase compared with that in the controls. Consequently, the gut microbiota is suggested to affect the sleep/wake architecture by altering the intestinal balance of neurotransmitters.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yukino", "last_name": "Ogawa", "name": null }, { "creator_type": "author", "first_name": "Chika", "last_name": "Miyoshi", "name": null }, { "creator_type": "author", "first_name": "Nozomu", "last_name": "Obana", "name": null }, { "creator_type": "author", "first_name": "Kaho", "last_name": "Yajima", "name": null }, { "creator_type": "author", "first_name": "Noriko", "last_name": "Hotta-Hirashima", "name": null }, { "creator_type": "author", "first_name": "Aya", "last_name": "Ikkyu", "name": null }, { "creator_type": "author", "first_name": "Satomi", "last_name": "Kanno", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Shinji", "last_name": "Fukuda", "name": null }, { "creator_type": "author", "first_name": "Masashi", "last_name": "Yanagisawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41598-020-76562-9" }, "pmcid": { "normalized": "PMC7659342" }, "pmid": { "normalized": "33177599" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Anti-Bacterial Agents", "descriptor_ui": "D000900", "major_topic": false }, { "descriptor": "Cecum", "descriptor_ui": "D002432", "major_topic": false }, { "descriptor": "Electroencephalography", "descriptor_ui": "D004569", "major_topic": false }, { "descriptor": "Gastrointestinal Microbiome", "descriptor_ui": "D000069196", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Metabolome", "descriptor_ui": "D055442", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Neurotransmitter Agents", "descriptor_ui": "D018377", "major_topic": false }, { "descriptor": "Sleep", "descriptor_ui": "D012890", "major_topic": false }, { "descriptor": "Sleep, REM", "descriptor_ui": "D012895", "major_topic": false }, { "descriptor": "Synaptic Transmission", "descriptor_ui": "D009435", "major_topic": false }, { "descriptor": "Wakefulness", "descriptor_ui": "D014851", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020 Nov 11", "date_precision": "day", "issue": "1", "normalized_date": "2020-11-11", "pages": "19554", "proceedings_title": null, "publisher": "", "title": "Scientific reports", "volume": "10", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Gut microbiota depletion by chronic antibiotic treatment alters the sleep/wake architecture and sleep EEG power spectra in mice.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Image segmentation is the pixel-by-pixel detection of objects, which is the most challenging but informative in the fundamental tasks of machine learning including image classification and object detection. Pixel-by-pixel segmentation is required to apply machine learning to support fetal cardiac ultrasound screening; we have to detect cardiac substructures precisely which are small and change shapes dynamically with fetal heartbeats, such as the ventricular septum. This task is difficult for general segmentation methods such as DeepLab v3+, and U-net. Hence, here we proposed a novel segmentation method named Cropping-Segmentation-Calibration (CSC) that is specific to the ventricular septum in ultrasound videos in this study. CSC employs the time-series information of videos and specific section information to calibrate the output of U-net. The actual sections of the ventricular septum were annotated in 615 frames from 421 normal fetal cardiac ultrasound videos of 211 pregnant women who were screened. The dataset was assigned a ratio of 2:1, which corresponded to a ratio of the training to test data, and three-fold cross-validation was conducted. The segmentation results of DeepLab v3+, U-net, and CSC were evaluated using the values of the mean intersection over union (mIoU), which were 0.0224, 0.1519, and 0.5543, respectively. The results reveal the superior performance of CSC.", "classifications": [ { "id": "Hamamoto", "label": "Group Hamamoto", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Ai", "last_name": "Dozen", "name": null }, { "creator_type": "author", "first_name": "Masaaki", "last_name": "Komatsu", "name": null }, { "creator_type": "author", "first_name": "Akira", "last_name": "Sakai", "name": null }, { "creator_type": "author", "first_name": "Reina", "last_name": "Komatsu", "name": null }, { "creator_type": "author", "first_name": "Kanto", "last_name": "Shozu", "name": null }, { "creator_type": "author", "first_name": "Hidenori", "last_name": "Machino", "name": null }, { "creator_type": "author", "first_name": "Suguru", "last_name": "Yasutomi", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Arakaki", "name": null }, { "creator_type": "author", "first_name": "Ken", "last_name": "Asada", "name": null }, { "creator_type": "author", "first_name": "Syuzo", "last_name": "Kaneko", "name": null }, { "creator_type": "author", "first_name": "Ryu", "last_name": "Matsuoka", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Aoki", "name": null }, { "creator_type": "author", "first_name": "Akihiko", "last_name": "Sekizawa", "name": null }, { "creator_type": "author", "first_name": "Ryuji", "last_name": "Hamamoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.3390/biom10111526" }, "pmcid": { "normalized": "PMC7695246" }, "pmid": { "normalized": "33171658" } }, "mesh": [ { "descriptor": "Deep Learning", "descriptor_ui": "D000077321", "major_topic": true }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Fetal Heart", "descriptor_ui": "D005318", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Image Processing, Computer-Assisted", "descriptor_ui": "D007091", "major_topic": true }, { "descriptor": "Pregnancy", "descriptor_ui": "D011247", "major_topic": false }, { "descriptor": "Ultrasonography, Prenatal", "descriptor_ui": "D016216", "major_topic": true }, { "descriptor": "Ventricular Septum", "descriptor_ui": "D054088", "major_topic": true } ], "publication": { "conference_name": null, "date": "2020 Nov 8", "date_precision": "day", "issue": "11", "normalized_date": "2020-11-08", "pages": "", "proceedings_title": null, "publisher": "", "title": "Biomolecules", "volume": "10", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Image Segmentation of the Ventricular Septum in Fetal Cardiac Ultrasound Videos Based on Deep Learning Using Time-Series Information.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Human germ cells perpetuate human genetic and epigenetic information. However, the underlying mechanism remains elusive, due to a lack of appropriate experimental systems. Here, we show that human primordial germ cell-like cells (hPGCLCs) derived from human-induced pluripotent stem cells (hiPSCs) can be propagated to at least ~10(6) -fold over a period of 4 months under a defined condition in vitro. During expansion, hPGCLCs maintain an early hPGC-like transcriptome and preserve their genome-wide DNA methylation profiles, most likely due to retention of maintenance DNA methyltransferase activity. These characteristics contrast starkly with those of mouse PGCLCs, which, under an analogous condition, show a limited propagation (up to ~50-fold) and persist only around 1 week, yet undergo cell-autonomous genome-wide DNA demethylation. Importantly, upon aggregation culture with mouse embryonic ovarian somatic cells in xenogeneic-reconstituted ovaries, expanded hPGCLCs initiate genome-wide DNA demethylation and differentiate into oogonia/gonocyte-like cells, demonstrating their germline potential. By creating a paradigm for hPGCLC expansion, our study uncovers critical divergences in expansion potential and the mechanism for epigenetic reprogramming between the human and mouse germ cell lineage.", "classifications": [ { "id": "Yamamoto", "label": "Group Yamamoto", "parent": "Toyoshima", "type": "group" }, { "id": "Toyoshima", "label": "Team Toyoshima", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yusuke", "last_name": "Murase", "name": null }, { "creator_type": "author", "first_name": "Yukihiro", "last_name": "Yabuta", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Ohta", "name": null }, { "creator_type": "author", "first_name": "Chika", "last_name": "Yamashiro", "name": null }, { "creator_type": "author", "first_name": "Tomonori", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Mitinori", "last_name": "Saitou", "name": null } ], "identifiers": { "doi": { "normalized": "10.15252/embj.2020104929" }, "pmcid": { "normalized": "PMC7604613" }, "pmid": { "normalized": "32954504" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "DNA Demethylation", "descriptor_ui": "D000073399", "major_topic": false }, { "descriptor": "DNA Methylation", "descriptor_ui": "D019175", "major_topic": false }, { "descriptor": "Embryonic Stem Cells", "descriptor_ui": "D053595", "major_topic": false }, { "descriptor": "Epigenesis, Genetic", "descriptor_ui": "D044127", "major_topic": false }, { "descriptor": "Epigenomics", "descriptor_ui": "D057890", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Genome", "descriptor_ui": "D016678", "major_topic": false }, { "descriptor": "Germ Cells", "descriptor_ui": "D005854", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Induced Pluripotent Stem Cells", "descriptor_ui": "D057026", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Ovary", "descriptor_ui": "D010053", "major_topic": false }, { "descriptor": "Pluripotent Stem Cells", "descriptor_ui": "D039904", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020 Nov 2", "date_precision": "day", "issue": "21", "normalized_date": "2020-11-02", "pages": "e104929", "proceedings_title": null, "publisher": "", "title": "The EMBO journal", "volume": "39", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Long-term expansion with germline potential of human primordial germ cell-like cells in vitro.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "As the physical properties and functionality of dipeptides differ from those of amino acids, they have attracted attention in metabolomics; however, their functions in vivo have not been clarified in detail. Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer, and its major cause is chronic hepatitis. This study was conducted to explore tumor-specific dipeptide characteristics by performing comprehensive dipeptide analysis in the tumor and surrounding nontumor tissue of patients with HCC. Dipeptides were analyzed by liquid chromatography tandem mass spectrometry and capillary electrophoresis tandem mass spectrometry. Principal component analysis using 236 detected dipeptides showed differences in the dipeptide profiles between nontumor and tumor tissues; however, no clear difference was observed in etiological comparison. In addition, the N- and C-terminal amino acid compositions of the detected dipeptides significantly differed, suggesting the substrate specificity of enzyme proteins, such as peptidase. Furthermore, hepatitis-derived HCC may show a characteristic dipeptide profile even before tumor formation. These results provide insight into HCC pathogenesis and may help identify novel biomarkers for diagnosis.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Ozawa", "name": null }, { "creator_type": "author", "first_name": "Akiyoshi", "last_name": "Hirayama", "name": null }, { "creator_type": "author", "first_name": "Futaba", "last_name": "Shoji", "name": null }, { "creator_type": "author", "first_name": "Midori", "last_name": "Maruyama", "name": null }, { "creator_type": "author", "first_name": "Kumi", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Hisami", "last_name": "Yamanaka-Okumura", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Tatano", "name": null }, { "creator_type": "author", "first_name": "Yuji", "last_name": "Morine", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Mitsuo", "last_name": "Shimada", "name": null }, { "creator_type": "author", "first_name": "Masaru", "last_name": "Tomita", "name": null } ], "identifiers": { "doi": { "normalized": "10.3390/metabo10110442" }, "pmcid": { "normalized": "PMC7692321" }, "pmid": { "normalized": "33139606" } }, "mesh": [], "publication": { "conference_name": null, "date": "2020 Nov 1", "date_precision": "day", "issue": "11", "normalized_date": "2020-11-01", "pages": "", "proceedings_title": null, "publisher": "", "title": "Metabolites", "volume": "10", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Comprehensive Dipeptide Analysis Revealed Cancer-Specific Profile in the Liver of Patients with Hepatocellular Carcinoma and Hepatitis.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The formation of vascular tubes is driven by extensive changes in endothelial cell (EC) shape. Here, we have identified a role of the actin-binding protein, Marcksl1, in modulating the mechanical properties of EC cortex to regulate cell shape and vessel structure during angiogenesis. Increasing and depleting Marcksl1 expression level in vivo results in an increase and decrease, respectively, in EC size and the diameter of microvessels. Furthermore, endothelial overexpression of Marcksl1 induces ectopic blebbing on both apical and basal membranes, during and after lumen formation, that is suppressed by reduced blood flow. High resolution imaging reveals that Marcksl1 promotes the formation of linear actin bundles and decreases actin density at the EC cortex. Our findings demonstrate that a balanced network of linear and branched actin at the EC cortex is essential in conferring cortical integrity to resist the deforming forces of blood flow to regulate vessel structure.", "classifications": [ { "id": "Okuda", "label": "Group Okuda", "parent": "Imayoshi", "type": "group" }, { "id": "Imayoshi", "label": "Team Imayoshi", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Igor", "last_name": "Kondrychyn", "name": null }, { "creator_type": "author", "first_name": "Douglas J.", "last_name": "Kelly", "name": null }, { "creator_type": "author", "first_name": "Nuria Taberner", "last_name": "Carretero", "name": null }, { "creator_type": "author", "first_name": "Akane", "last_name": "Nomori", "name": null }, { "creator_type": "author", "first_name": "Kagayaki", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Jeronica", "last_name": "Chong", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Nakajima", "name": null }, { "creator_type": "author", "first_name": "Satoru", "last_name": "Okuda", "name": null }, { "creator_type": "author", "first_name": "Naoki", "last_name": "Mochizuki", "name": null }, { "creator_type": "author", "first_name": "Li-Kun", "last_name": "Phng", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41467-020-19308-5" }, "pmcid": { "normalized": "PMC7603353" }, "pmid": { "normalized": "33127887" } }, "mesh": [ { "descriptor": "Actins", "descriptor_ui": "D000199", "major_topic": false }, { "descriptor": "Actomyosin", "descriptor_ui": "D000205", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Animals, Genetically Modified", "descriptor_ui": "D030801", "major_topic": false }, { "descriptor": "Blood Vessels", "descriptor_ui": "D001808", "major_topic": false }, { "descriptor": "Calmodulin-Binding Proteins", "descriptor_ui": "D002148", "major_topic": false }, { "descriptor": "Endothelial Cells", "descriptor_ui": "D042783", "major_topic": false }, { "descriptor": "Gene Expression Regulation, Developmental", "descriptor_ui": "D018507", "major_topic": false }, { "descriptor": "Hemodynamics", "descriptor_ui": "D006439", "major_topic": false }, { "descriptor": "Microfilament Proteins", "descriptor_ui": "D008840", "major_topic": false }, { "descriptor": "Models, Animal", "descriptor_ui": "D023421", "major_topic": false }, { "descriptor": "Transcriptome", "descriptor_ui": "D059467", "major_topic": false }, { "descriptor": "Zebrafish", "descriptor_ui": "D015027", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020 Oct 30", "date_precision": "day", "issue": "1", "normalized_date": "2020-10-30", "pages": "5476", "proceedings_title": null, "publisher": "", "title": "Nature communications", "volume": "11", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Marcksl1 modulates endothelial cell mechanoresponse to haemodynamic forces to control blood vessel shape and size.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Adaptive optics is being applied widely to a range of microscopies in order to improve imaging quality in the presence of specimen-induced aberrations. We present here the first implementation of wavefront-sensorless adaptive optics for a laser-free, aperture correlation, spinning disk microscope. This widefield method provides confocal-like optical sectioning through use of a patterned disk in the illumination and detection paths. Like other high-resolution microscopes, its operation is compromised by aberrations due to refractive index mismatch and variations within the specimen. Correction of such aberrations shows improved signal level, contrast and resolution.", "classifications": [ { "id": "Fujita", "label": "Group Fujita", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Syed Asad", "last_name": "Hussain", "name": null }, { "creator_type": "author", "first_name": "Toshiki", "last_name": "Kubo", "name": null }, { "creator_type": "author", "first_name": "Nicholas", "last_name": "Hall", "name": null }, { "creator_type": "author", "first_name": "Dalia", "last_name": "Gala", "name": null }, { "creator_type": "author", "first_name": "Karen", "last_name": "Hampson", "name": null }, { "creator_type": "author", "first_name": "Richard", "last_name": "Parton", "name": null }, { "creator_type": "author", "first_name": "Mick A.", "last_name": "Phillips", "name": null }, { "creator_type": "author", "first_name": "Matthew", "last_name": "Wincott", "name": null }, { "creator_type": "author", "first_name": "Katsumasa", "last_name": "Fujita", "name": null }, { "creator_type": "author", "first_name": "Ilan", "last_name": "Davis", "name": null }, { "creator_type": "author", "first_name": "Ian", "last_name": "Dobbie", "name": null }, { "creator_type": "author", "first_name": "Martin J.", "last_name": "Booth", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/jmi.12976" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "33128278" } }, "mesh": [ { "descriptor": "Lasers", "descriptor_ui": "D007834", "major_topic": false }, { "descriptor": "Microscopy", "descriptor_ui": "D008853", "major_topic": true }, { "descriptor": "Optics and Photonics", "descriptor_ui": "D055095", "major_topic": true }, { "descriptor": "Refractometry", "descriptor_ui": "D012031", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020 Oct 30", "date_precision": "day", "issue": "", "normalized_date": "2020-10-30", "pages": "", "proceedings_title": null, "publisher": "", "title": "Journal of microscopy", "volume": "", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Wavefront-sensorless adaptive optics with a laser-free spinning disk confocal microscope.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Light-induced extrasynaptic dopamine release in the retina reduces adenosine 3',5'-cyclic monophosphate (cAMP) in rod photoreceptor cells, which is thought to mediate light-dependent desensitization. However, the fine time course of the cAMP dynamics in rods remains elusive due to technical difficulty. Here, we visualized the spatiotemporal regulation of cAMP-dependent protein kinase (PKA) in mouse rods by two-photon live imaging of retinal explants of PKAchu mice, which express a fluorescent biosensor for PKA. Unexpectedly, in addition to the light-on-induced suppression, we observed prominent light-off-induced PKA activation. This activation required photopic light intensity and was confined to the illuminated rods. The estimated maximum spectral sensitivity of 489 nm and loss of the light-off-induced PKA activation in rod-transducin-knockout retinas strongly suggest the involvement of rhodopsin. In support of this notion, rhodopsin-deficient retinal explants showed only the light-on-induced PKA suppression. Taken together, these results suggest that, upon photopic light stimulation, rhodopsin and dopamine signals are integrated to shape the light-off-induced cAMP production and following PKA activation. This may support the dark adaptation of rods.", "classifications": [], "creators": [ { "creator_type": "contributor", "first_name": "Shinya", "last_name": "Sato", "name": null }, { "creator_type": "contributor", "first_name": "Takahiro", "last_name": "Yamashita", "name": null }, { "creator_type": "contributor", "first_name": "Michiyuki", "last_name": "Matsuda", "name": null } ], "identifiers": { "doi": { "normalized": "10.1073/pnas.2009164117" }, "pmcid": { "normalized": "PMC7604457" }, "pmid": { "normalized": "33046651" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cyclic AMP-Dependent Protein Kinases", "descriptor_ui": "D017868", "major_topic": false }, { "descriptor": "Dopamine", "descriptor_ui": "D004298", "major_topic": false }, { "descriptor": "Enzyme Activation", "descriptor_ui": "D004789", "major_topic": false }, { "descriptor": "Mice, Transgenic", "descriptor_ui": "D008822", "major_topic": false }, { "descriptor": "Microscopy, Fluorescence, Multiphoton", "descriptor_ui": "D036641", "major_topic": false }, { "descriptor": "Retinal Rod Photoreceptor Cells", "descriptor_ui": "D017948", "major_topic": false }, { "descriptor": "Rhodopsin", "descriptor_ui": "D012243", "major_topic": false }, { "descriptor": "Transducin", "descriptor_ui": "D015293", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020 Oct 27", "date_precision": "day", "issue": "43", "normalized_date": "2020-10-27", "pages": "26996-27003", "proceedings_title": null, "publisher": "", "title": "Proceedings of the National Academy of Sciences of the United States of America", "volume": "117", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Rhodopsin-mediated light-off-induced protein kinase A activation in mouse rod photoreceptor cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Histone modifications deposited by the Polycomb repressive complex 2 (PRC2) play a critical role in the control of growth, development, and adaptation to environmental fluctuations of most multicellular eukaryotes. The catalytic activity of PRC2 is counteracted by Jumonji-type (JMJ) histone demethylases, which shapes the genomic distribution of H3K27me3. Here, we show that two JMJ histone demethylases in Arabidopsis, EARLY FLOWERING 6 (ELF6) and RELATIVE OF EARLY FLOWERING 6 (REF6), play distinct roles in H3K27me3 and H3K27me1 homeostasis. We show that failure to reset these chromatin marks during sexual reproduction results in the transgenerational inheritance of histone marks, which cause a loss of DNA methylation at heterochromatic loci and transposon activation. Thus, Jumonji-type histone demethylases play a dual role in plants by helping to maintain transcriptional states through development and safeguard genome integrity during sexual reproduction.", "classifications": [ { "id": "Ueda", "label": "Group Ueda", "parent": "Ueda", "type": "group" }, { "id": "Ueda", "label": "Team Ueda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Javier", "last_name": "Antunez-Sanchez", "name": null }, { "creator_type": "author", "first_name": "Matthew", "last_name": "Naish", "name": null }, { "creator_type": "author", "first_name": "Juan Sebastian", "last_name": "Ramirez-Prado", "name": null }, { "creator_type": "author", "first_name": "Sho", "last_name": "Ohno", "name": null }, { "creator_type": "author", "first_name": "Ying", "last_name": "Huang", "name": null }, { "creator_type": "author", "first_name": "Alexander", "last_name": "Dawson", "name": null }, { "creator_type": "author", "first_name": "Korawit", "last_name": "Opassathian", "name": null }, { "creator_type": "author", "first_name": "Deborah", "last_name": "Manza-Mianza", "name": null }, { "creator_type": "author", "first_name": "Federico", "last_name": "Ariel", "name": null }, { "creator_type": "author", "first_name": "Cecile", "last_name": "Raynaud", "name": null }, { "creator_type": "author", "first_name": "Anjar", "last_name": "Wibowo", "name": null }, { "creator_type": "author", "first_name": "Josquin", "last_name": "Daron", "name": null }, { "creator_type": "author", "first_name": "Minako", "last_name": "Ueda", "name": null }, { "creator_type": "author", "first_name": "David", "last_name": "Latrasse", "name": null }, { "creator_type": "author", "first_name": "R. Keith", "last_name": "Slotkin", "name": null }, { "creator_type": "author", "first_name": "Detlef", "last_name": "Weigel", "name": null }, { "creator_type": "author", "first_name": "Moussa", "last_name": "Benhamed", "name": null }, { "creator_type": "author", "first_name": "Jose", "last_name": "Gutierrez-Marcos", "name": null } ], "identifiers": { "doi": { "normalized": "10.7554/elife.58533" }, "pmcid": { "normalized": "PMC7671693" }, "pmid": { "normalized": "33107825" } }, "mesh": [ { "descriptor": "Arabidopsis", "descriptor_ui": "D017360", "major_topic": false }, { "descriptor": "Arabidopsis Proteins", "descriptor_ui": "D029681", "major_topic": false }, { "descriptor": "Gene Expression Regulation, Plant", "descriptor_ui": "D018506", "major_topic": false }, { "descriptor": "Genome, Plant", "descriptor_ui": "D018745", "major_topic": true }, { "descriptor": "Histones", "descriptor_ui": "D006657", "major_topic": false }, { "descriptor": "Jumonji Domain-Containing Histone Demethylases", "descriptor_ui": "D056484", "major_topic": false }, { "descriptor": "Polycomb Repressive Complex 2", "descriptor_ui": "D063151", "major_topic": false }, { "descriptor": "Transcription Factors", "descriptor_ui": "D014157", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020 Oct 27", "date_precision": "day", "issue": "", "normalized_date": "2020-10-27", "pages": "", "proceedings_title": null, "publisher": "", "title": "eLife", "volume": "9", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "A new role for histone demethylases in the maintenance of plant genome integrity.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The selective carbon dioxide (CO(2)) absorption properties of ionic liquids (ILs) are highly pertinent to the development of methods to capture CO(2). Although it has been reported that fluorinated components give ILs enhanced CO(2) solubilities, it has been challenging to gain a deep understanding of the interactions occurring between ILs and CO(2). In this investigation, we have utilized the soft crystalline material [Cu(NTf(2))(2)(bpp)(2)] (NTf(2)(‒) = bis(trifluoromethylsulfonyl)imide, bpp = 1,3-bis-(4-pyridyl)propane) as a surrogate for single-crystal X-ray diffraction analysis to visualize interactions occurring between CO(2) and NTf(2)(‒), the fluorinated IL component that is responsible for high CO(2) solubility. Analysis of the structure of a CO(2)-loaded crystal reveals that CO(2) interacts with both fluorine and oxygen atoms of NTf(2)(‒) anions in a trans rather than cis conformation about the S-N bond. Theoretical analysis of the structure of the CO(2)-loaded crystal indicates that dispersion and electrostatic interactions exist between CO(2) and the framework. The overall results provide important insight into understanding and improving the CO(2) absorption properties of ILs.", "classifications": [ { "id": "Hijikata", "label": "Group Hijikata", "parent": "Tsuchiya", "type": "group" }, { "id": "Tsuchiya", "label": "Team Tsuchiya", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Xin", "last_name": "Zheng", "name": null }, { "creator_type": "author", "first_name": "Katsuo", "last_name": "Fukuhara", "name": null }, { "creator_type": "author", "first_name": "Yuh", "last_name": "Hijikata", "name": null }, { "creator_type": "author", "first_name": "Jenny", "last_name": "Pirillo", "name": null }, { "creator_type": "author", "first_name": "Hiroyasu", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Kiyonori", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Shin-Ichiro", "last_name": "Noro", "name": null }, { "creator_type": "author", "first_name": "Takayoshi", "last_name": "Nakamura", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s42004-020-00390-1" }, "pmcid": { "normalized": "PMC9814135" }, "pmid": { "normalized": "36703407" } }, "mesh": [], "publication": { "conference_name": null, "date": "2020 Oct 27", "date_precision": "day", "issue": "1", "normalized_date": "2020-10-27", "pages": "143", "proceedings_title": null, "publisher": "", "title": "Communications chemistry", "volume": "3", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Understanding the interactions between the bis(trifluoromethylsulfonyl)imide anion and absorbed CO(2) using X-ray diffraction analysis of a soft crystal surrogate.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "For over the past 30 years, generalized two-dimensional correlation spectroscopy has formed an active and widespread research area. One of the most attractive properties of this method is that one can determine the sequential order of signal changes. But the determination of the sequential order has only been done manually for several arbitrarily chosen bands. In this paper, we develop a method to automatically determine the sequential order of all of the band intensity changes, and we applied this method to band changes of vibration spectra. This method will open a door to analyze more complicated signals often seen in life phenomena.", "classifications": [ { "id": "Nakabayashi", "label": "Group Nakabayashi", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Daisuke", "last_name": "Miyata", "name": null }, { "creator_type": "author", "first_name": "Takakazu", "last_name": "Nakabayashi", "name": null }, { "creator_type": "author", "first_name": "Shin-Ichi", "last_name": "Morita", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/acs.jcim.0c00627" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "32986417" } }, "mesh": [ { "descriptor": "Spectrum Analysis", "descriptor_ui": "D013057", "major_topic": false }, { "descriptor": "Vibration", "descriptor_ui": "D014732", "major_topic": true } ], "publication": { "conference_name": null, "date": "2020 Oct 26", "date_precision": "day", "issue": "10", "normalized_date": "2020-10-26", "pages": "5070-5079", "proceedings_title": null, "publisher": "", "title": "Journal of chemical information and modeling", "volume": "60", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Automatic Determination of the Sequential Order of Dynamic Data and Its Application to Vibrational Spectroscopy.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Skeletal muscle adaptation is mediated by cooperative regulation of metabolism, signal transduction, and gene expression. However, the global regulatory mechanism remains unclear. To address this issue, we performed electrical pulse stimulation (EPS) in differentiated C2C12 myotubes at low and high frequency, carried out metabolome and transcriptome analyses, and investigated phosphorylation status of signaling molecules. EPS triggered extensive and specific changes in metabolites, signaling phosphorylation, and gene expression during and after EPS in a frequency-dependent manner. We constructed trans-omic network by integrating these data and found selective activation of the pentose phosphate pathway including metabolites, upstream signaling molecules, and gene expression of metabolic enzymes after high-frequency EPS. We experimentally validated that activation of these molecules after high-frequency EPS was dependent on reactive oxygen species (ROS). Thus, the trans-omic analysis revealed ROS-dependent activation in signal transduction, metabolome, and transcriptome after high-frequency EPS in C2C12 myotubes, shedding light on possible mechanisms of muscle adaptation.", "classifications": [ { "id": "Kuroda", "label": "Group Kuroda", "parent": "Kuroda", "type": "group" }, { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Daisuke", "last_name": "Hoshino", "name": null }, { "creator_type": "author", "first_name": "Kentaro", "last_name": "Kawata", "name": null }, { "creator_type": "author", "first_name": "Katsuyuki", "last_name": "Kunida", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Hatano", "name": null }, { "creator_type": "author", "first_name": "Katsuyuki", "last_name": "Yugi", "name": null }, { "creator_type": "author", "first_name": "Takumi", "last_name": "Wada", "name": null }, { "creator_type": "author", "first_name": "Masashi", "last_name": "Fujii", "name": null }, { "creator_type": "author", "first_name": "Takanori", "last_name": "Sano", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Yasuro", "last_name": "Furuichi", "name": null }, { "creator_type": "author", "first_name": "Yasuko", "last_name": "Manabe", "name": null }, { "creator_type": "author", "first_name": "Yutaka", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Nobuharu L.", "last_name": "Fujii", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Kuroda", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.isci.2020.101558" }, "pmcid": { "normalized": "PMC7522805" }, "pmid": { "normalized": "33083727" } }, "mesh": [], "publication": { "conference_name": null, "date": "2020 Oct 23", "date_precision": "day", "issue": "10", "normalized_date": "2020-10-23", "pages": "101558", "proceedings_title": null, "publisher": "", "title": "iScience", "volume": "23", "year": 2020 }, "ssbd": { "database": [ "ssbd-database-000185" ], "repository": [ "ssbd-repos-000185" ] }, "title": "Trans-omic Analysis Reveals ROS-Dependent Pentose Phosphate Pathway Activation after High-Frequency Electrical Stimulation in C2C12 Myotubes.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "With the development of digital technology, media multitasking behaviour, which is using two or more media simultaneously, has become more commonplace. There are two opposing hypotheses of media multitasking with regard to its impact on attention. One hypothesis claims that media multitasking can strengthen attention control, and the other claims heavy media multitaskers are less able to focus on relevant tasks in the presence of distractors. A total of 103 healthy subjects took part in this study. We measured the Media Multitasking Index (MMI) and subjects performed the continuous performance test. Resting state and oddball task functional MRI were conducted to analyse functional connectivity in the dorsal attention network, and the degree centrality (DC) was calculated using graph theory analysis. We found that the DCs in the dorsal attention network were higher during resting state than during the oddball task. Furthermore, the DCs during the task were positively correlated with the MMI. These results indicated that the DC reduction from resting state to the oddball task in high media multitaskers was attenuated compared with low media multitaskers. This study not only reveals more about the neurophysiology of media multitasking, but could also indicate brain biomarkers of media multitasking behaviour.", "classifications": [ { "id": "Fujiwara", "label": "Group Fujiwara", "parent": "Fujiwara", "type": "group" }, { "id": "Fujiwara", "label": "Team Fujiwara", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Kei", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Naoya", "last_name": "Oishi", "name": null }, { "creator_type": "author", "first_name": "Sayaka", "last_name": "Yoshimura", "name": null }, { "creator_type": "author", "first_name": "Tsukasa", "last_name": "Ueno", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Miyagi", "name": null }, { "creator_type": "author", "first_name": "Toshiya", "last_name": "Murai", "name": null }, { "creator_type": "author", "first_name": "Hironobu", "last_name": "Fujiwara", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41598-020-75091-9" }, "pmcid": { "normalized": "PMC7582949" }, "pmid": { "normalized": "33093496" } }, "mesh": [ { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Attention", "descriptor_ui": "D001288", "major_topic": false }, { "descriptor": "Brain", "descriptor_ui": "D001921", "major_topic": false }, { "descriptor": "Cognition", "descriptor_ui": "D003071", "major_topic": false }, { "descriptor": "Communications Media", "descriptor_ui": "D003146", "major_topic": false }, { "descriptor": "Executive Function", "descriptor_ui": "D056344", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Memory", "descriptor_ui": "D008568", "major_topic": false }, { "descriptor": "Nerve Net", "descriptor_ui": "D009415", "major_topic": false }, { "descriptor": "Task Performance and Analysis", "descriptor_ui": "D013647", "major_topic": true } ], "publication": { "conference_name": null, "date": "2020 Oct 22", "date_precision": "day", "issue": "1", "normalized_date": "2020-10-22", "pages": "17992", "proceedings_title": null, "publisher": "", "title": "Scientific reports", "volume": "10", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Relationship between media multitasking and functional connectivity in the dorsal attention network.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Cell-cycle entry relies on an orderly progression of signaling events. To start, cells first activate the kinase cyclin D-CDK4/6, which leads to eventual inactivation of the retinoblastoma protein Rb. Hours later, cells inactivate APC/C(CDH1) and cross the final commitment point. However, many cells with genetically deleted cyclin Ds, which activate and confer specificity to CDK4/6, can compensate and proliferate. Despite its importance in cancer, how this entry mechanism operates remains poorly characterized, and whether cells use this path under normal conditions remains unknown. Here, using single-cell microscopy, we demonstrate that cells with acutely inhibited CDK4/6 enter the cell cycle with a slowed and fluctuating cyclin E-CDK2 activity increase. Surprisingly, with low CDK4/6 activity, the order of APC/C(CDH1) and Rb inactivation is reversed in both cell lines and wild-type mice. Finally, we show that as a consequence of this signaling inversion, Rb inactivation replaces APC/C(CDH1) inactivation as the point of no return. Together, we elucidate the molecular steps that enable cell-cycle entry without CDK4/6 activity. Our findings not only have implications in cancer resistance, but also reveal temporal plasticity underlying the G1 regulatory circuit.", "classifications": [], "creators": [ { "creator_type": "author", "first_name": "Chad", "last_name": "Liu", "name": null }, { "creator_type": "author", "first_name": "Yumi", "last_name": "Konagaya", "name": null }, { "creator_type": "author", "first_name": "Mingyu", "last_name": "Chung", "name": null }, { "creator_type": "author", "first_name": "Leighton H.", "last_name": "Daigh", "name": null }, { "creator_type": "author", "first_name": "Yilin", "last_name": "Fan", "name": null }, { "creator_type": "author", "first_name": "Hee Won", "last_name": "Yang", "name": null }, { "creator_type": "author", "first_name": "Kenta", "last_name": "Terai", "name": null }, { "creator_type": "author", "first_name": "Michiyuki", "last_name": "Matsuda", "name": null }, { "creator_type": "author", "first_name": "Tobias", "last_name": "Meyer", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41467-020-18966-9" }, "pmcid": { "normalized": "PMC7576148" }, "pmid": { "normalized": "33082317" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "Cell Proliferation", "descriptor_ui": "D049109", "major_topic": false }, { "descriptor": "Cyclin-Dependent Kinase 4", "descriptor_ui": "D051358", "major_topic": false }, { "descriptor": "Cyclin-Dependent Kinase 6", "descriptor_ui": "D051361", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "G1 Phase", "descriptor_ui": "D016193", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Retinoblastoma Protein", "descriptor_ui": "D016160", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020 Oct 20", "date_precision": "day", "issue": "1", "normalized_date": "2020-10-20", "pages": "5305", "proceedings_title": null, "publisher": "", "title": "Nature communications", "volume": "11", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Altered G1 signaling order and commitment point in cells proliferating without CDK4/6 activity.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Salivary metabolomics have provided the potentials to detect both oral and systemic diseases. Capillary electrophoresis time-of-flight-mass spectrometry (CE-TOFMS) enables the identification and quantification of various charged metabolites. This method has been employed to biomarker discoveries using human saliva samples, especially for various types of cancers. The untargeted analysis contributes to finding new biomarkers. i.e., the analysis of all detectable signals including both known and unknown metabolites extends the coverage of metabolite to be observed. However, the observed data includes thousands of peaks. Besides, non-linear migration time fluctuation and skewed peaks are caused by the sample condition. The presented pretreatment protocols of saliva samples enhance the reproducibility of migration time drift, which facilitates the matching peaks across the samples and also results in reproducible absolute concentrations of the detected metabolites. The described protocols are utilized not only for saliva but for any liquid samples with slight modifications.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Masahiro", "last_name": "Sugimoto", "name": null }, { "creator_type": "author", "first_name": "Sana", "last_name": "Ota", "name": null }, { "creator_type": "author", "first_name": "Miku", "last_name": "Kaneko", "name": null }, { "creator_type": "author", "first_name": "Ayame", "last_name": "Enomoto", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null } ], "identifiers": { "doi": { "normalized": "10.21769/bioprotoc.3797" }, "pmcid": { "normalized": "PMC7842545" }, "pmid": { "normalized": "33659451" } }, "mesh": [], "publication": { "conference_name": null, "date": "2020 Oct 20", "date_precision": "day", "issue": "20", "normalized_date": "2020-10-20", "pages": "e3797", "proceedings_title": null, "publisher": "", "title": "Bio-protocol", "volume": "10", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Quantification of Salivary Charged Metabolites using Capillary Electrophoresis Time-of-flight-mass Spectrometry.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "During embryogenesis, cells repeatedly divide and dynamically change their positions in three-dimensional (3D) space. A robust and accurate algorithm to acquire the 3D positions of the cells would help to reveal the mechanisms of embryogenesis. To acquire quantitative criteria of embryogenesis from time-series 3D microscopic images, image processing algorithms such as segmentation have been applied. Because the cells in embryos are considerably crowded, an algorithm to segment individual cells in detail and accurately is needed. To quantify the nuclear region of every cell from a time-series 3D fluorescence microscopic image of living cells, we developed QCANet, a convolutional neural network-based segmentation algorithm for 3D fluorescence bioimages. We demonstrated that QCANet outperformed 3D Mask R-CNN, which is currently considered as the best algorithm of instance segmentation. We showed that QCANet can be applied not only to developing mouse embryos but also to developing embryos of two other model species. Using QCANet, we were able to extract several quantitative criteria of embryogenesis from 11 early mouse embryos. We showed that the extracted criteria could be used to evaluate the differences between individual embryos. This study contributes to the development of fundamental approaches for assessing embryogenesis on the basis of extracted quantitative criteria.", "classifications": [ { "id": "JPMJCR1927", "label": "JPMJCR1927", "researcher": "Yuichi Wakamoto", "type": "grant" }, { "id": "Kobayashi", "label": "Group Kobayashi", "parent": "Wakamoto", "type": "group" }, { "id": "Wakamoto", "label": "Group Wakamoto", "parent": "Wakamoto", "type": "group" }, { "id": "Wakamoto", "label": "Team Wakamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yuta", "last_name": "Tokuoka", "name": null }, { "creator_type": "author", "first_name": "Takahiro G.", "last_name": "Yamada", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Mashiko", "name": null }, { "creator_type": "author", "first_name": "Zenki", "last_name": "Ikeda", "name": null }, { "creator_type": "author", "first_name": "Noriko F.", "last_name": "Hiroi", "name": null }, { "creator_type": "author", "first_name": "Tetsuya J.", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Kazuo", "last_name": "Yamagata", "name": null }, { "creator_type": "author", "first_name": "Akira", "last_name": "Funahashi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41540-020-00152-8" }, "pmcid": { "normalized": "PMC7575569" }, "pmid": { "normalized": "33082352" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Nucleus", "descriptor_ui": "D002467", "major_topic": false }, { "descriptor": "Embryo, Mammalian", "descriptor_ui": "D004622", "major_topic": false }, { "descriptor": "Embryonic Development", "descriptor_ui": "D047108", "major_topic": true }, { "descriptor": "Imaging, Three-Dimensional", "descriptor_ui": "D021621", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Microscopy, Fluorescence", "descriptor_ui": "D008856", "major_topic": false }, { "descriptor": "Neural Networks, Computer", "descriptor_ui": "D016571", "major_topic": true } ], "publication": { "conference_name": null, "date": "2020 Oct 20", "date_precision": "day", "issue": "1", "normalized_date": "2020-10-20", "pages": "32", "proceedings_title": null, "publisher": "", "title": "NPJ systems biology and applications", "volume": "6", "year": 2020 }, "ssbd": { "database": [ "ssbd-database-000244" ], "repository": [ "ssbd-repos-000244" ] }, "title": "3D convolutional neural networks-based segmentation to acquire quantitative criteria of the nucleus during mouse embryogenesis.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Resilience is a dynamic process that enables organisms to cope with demanding environments. Resting-state functional MRI (fMRI) studies have demonstrated a negative correlation between resilience and functional connectivities (FCs) within the default mode network (DMN). Considering the on-demand recruitment process of resilience, dynamic changes in FCs during cognitive load increases may reflect essential aspects of resilience. We compared DMN FC changes in resting and task states and their association with resilience. Eighty-nine healthy volunteers completed the Connor-Davidson Resilience Scale (CD-RISC) and an fMRI with an auditory oddball task. The fMRI time series was divided into resting and task periods. We focused on FC changes between the latter half of the resting period and the former half of the task phase (switching), and between the former and latter half of the task phase (sustaining). FCs within the ventral DMN significantly increased during \"switching\" and decreased during \"sustaining\". For FCs between the retrosplenial/posterior cingulate and the parahippocampal cortex, increased FC during switching was negatively correlated with CD-RISC scores. In individuals with higher resilience, ventral DMN connectivities were more stable and homeostatic in the face of cognitive demand. The dynamic profile of DMN FCs may represent a novel biomarker of resilience.", "classifications": [ { "id": "Fujiwara", "label": "Group Fujiwara", "parent": "Fujiwara", "type": "group" }, { "id": "Fujiwara", "label": "Team Fujiwara", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Takashi", "last_name": "Miyagi", "name": null }, { "creator_type": "author", "first_name": "Naoya", "last_name": "Oishi", "name": null }, { "creator_type": "author", "first_name": "Kei", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Tsukasa", "last_name": "Ueno", "name": null }, { "creator_type": "author", "first_name": "Sayaka", "last_name": "Yoshimura", "name": null }, { "creator_type": "author", "first_name": "Toshiya", "last_name": "Murai", "name": null }, { "creator_type": "author", "first_name": "Hironobu", "last_name": "Fujiwara", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41598-020-74283-7" }, "pmcid": { "normalized": "PMC7576164" }, "pmid": { "normalized": "33082442" } }, "mesh": [ { "descriptor": "Adolescent", "descriptor_ui": "D000293", "major_topic": false }, { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Brain", "descriptor_ui": "D001921", "major_topic": false }, { "descriptor": "Brain Mapping", "descriptor_ui": "D001931", "major_topic": false }, { "descriptor": "Cognition", "descriptor_ui": "D003071", "major_topic": false }, { "descriptor": "Default Mode Network", "descriptor_ui": "D000082702", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Magnetic Resonance Imaging", "descriptor_ui": "D008279", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Neuropsychological Tests", "descriptor_ui": "D009483", "major_topic": false }, { "descriptor": "Resilience, Psychological", "descriptor_ui": "D055500", "major_topic": true }, { "descriptor": "Young Adult", "descriptor_ui": "D055815", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020 Oct 20", "date_precision": "day", "issue": "1", "normalized_date": "2020-10-20", "pages": "17760", "proceedings_title": null, "publisher": "", "title": "Scientific reports", "volume": "10", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Psychological resilience is correlated with dynamic changes in functional connectivity within the default mode network during a cognitive task.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Mortality attributed to lung cancer accounts for a large fraction of cancer deaths worldwide. With increasing mortality figures, the accurate prediction of prognosis has become essential. In recent years, multi-omics analysis has emerged as a useful survival prediction tool. However, the methodology relevant to multi-omics analysis has not yet been fully established and further improvements are required for clinical applications. In this study, we developed a novel method to accurately predict the survival of patients with lung cancer using multi-omics data. With unsupervised learning techniques, survival-associated subtypes in non-small cell lung cancer were first detected using the multi-omics datasets from six categories in The Cancer Genome Atlas (TCGA). The new subtypes, referred to as integration survival subtypes, clearly divided patients into longer and shorter-surviving groups (log-rank test: p = 0.003) and we confirmed that this is independent of histopathological classification (Chi-square test of independence: p = 0.94). Next, an attempt was made to detect the integration survival subtypes using only one categorical dataset. Our machine learning model that was only trained on the reverse phase protein array (RPPA) could accurately predict the integration survival subtypes (AUC = 0.99). The predicted subtypes could also distinguish between high and low risk patients (log-rank test: p = 0.012). Overall, this study explores novel potentials of multi-omics analysis to accurately predict the prognosis of patients with lung cancer.", "classifications": [ { "id": "Hamamoto", "label": "Group Hamamoto", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Satoshi", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Ken", "last_name": "Asada", "name": null }, { "creator_type": "author", "first_name": "Ken", "last_name": "Takasawa", "name": null }, { "creator_type": "author", "first_name": "Ryo", "last_name": "Shimoyama", "name": null }, { "creator_type": "author", "first_name": "Akira", "last_name": "Sakai", "name": null }, { "creator_type": "author", "first_name": "Amina", "last_name": "Bolatkan", "name": null }, { "creator_type": "author", "first_name": "Norio", "last_name": "Shinkai", "name": null }, { "creator_type": "author", "first_name": "Kazuma", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Masaaki", "last_name": "Komatsu", "name": null }, { "creator_type": "author", "first_name": "Syuzo", "last_name": "Kaneko", "name": null }, { "creator_type": "author", "first_name": "Jun", "last_name": "Sese", "name": null }, { "creator_type": "author", "first_name": "Ryuji", "last_name": "Hamamoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.3390/biom10101460" }, "pmcid": { "normalized": "PMC7603376" }, "pmid": { "normalized": "33086649" } }, "mesh": [ { "descriptor": "Carcinoma, Non-Small-Cell Lung", "descriptor_ui": "D002289", "major_topic": false }, { "descriptor": "Deep Learning", "descriptor_ui": "D000077321", "major_topic": true }, { "descriptor": "Disease-Free Survival", "descriptor_ui": "D018572", "major_topic": false }, { "descriptor": "DNA Methylation", "descriptor_ui": "D019175", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Genomics", "descriptor_ui": "D023281", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Machine Learning", "descriptor_ui": "D000069550", "major_topic": true }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Models, Theoretical", "descriptor_ui": "D008962", "major_topic": false }, { "descriptor": "Prognosis", "descriptor_ui": "D011379", "major_topic": true }, { "descriptor": "Protein Array Analysis", "descriptor_ui": "D040081", "major_topic": false }, { "descriptor": "Proteomics", "descriptor_ui": "D040901", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020 Oct 19", "date_precision": "day", "issue": "10", "normalized_date": "2020-10-19", "pages": "", "proceedings_title": null, "publisher": "", "title": "Biomolecules", "volume": "10", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Predicting Deep Learning Based Multi-Omics Parallel Integration Survival Subtypes in Lung Cancer Using Reverse Phase Protein Array Data.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Metal node design is crucial for obtaining structurally diverse coordination polymers (CPs) and metal-organic frameworks with desirable properties; however, Fe(II) ions are exclusively six-coordinated. Herein, we present a cyanide-bridged three-dimensional (3D) CP, FePd(CN)(4) , bearing four-coordinate Fe(II) ions, which is synthesized by thermal treatment of a two-dimensional (2D) six-coordinate Fe(II) CP, Fe(H(2) O)(2) Pd(CN)(4) ⋅4 H(2) O, to remove water molecules. Atomic-resolution transmission electron microscopy and powder X-ray and neutron diffraction measurements revealed that the FePd(CN)(4) structure is composed of a two-fold interpenetrated PtS topology network, where the Fe(II) center demonstrates an intermediate geometry between tetrahedral and square-planar coordination. This four-coordinate Fe(II) center with the distorted geometry can act as a thermo-responsive flexible node in the PtS network.", "classifications": [ { "id": "Hijikata", "label": "Group Hijikata", "parent": "Tsuchiya", "type": "group" }, { "id": "Tsuchiya", "label": "Team Tsuchiya", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Ryo", "last_name": "Ohtani", "name": null }, { "creator_type": "author", "first_name": "Hiromu", "last_name": "Matsunari", "name": null }, { "creator_type": "author", "first_name": "Takafumi", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Kimoto", "name": null }, { "creator_type": "author", "first_name": "Masaaki", "last_name": "Isobe", "name": null }, { "creator_type": "author", "first_name": "Kotaro", "last_name": "Fujii", "name": null }, { "creator_type": "author", "first_name": "Masatomo", "last_name": "Yashima", "name": null }, { "creator_type": "author", "first_name": "Susumu", "last_name": "Fujii", "name": null }, { "creator_type": "author", "first_name": "Akihide", "last_name": "Kuwabara", "name": null }, { "creator_type": "author", "first_name": "Yuh", "last_name": "Hijikata", "name": null }, { "creator_type": "author", "first_name": "Shin-Ichiro", "last_name": "Noro", "name": null }, { "creator_type": "author", "first_name": "Masaaki", "last_name": "Ohba", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Kageyama", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Hayami", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/anie.202008187" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "32662185" } }, "mesh": [], "publication": { "conference_name": null, "date": "2020 Oct 19", "date_precision": "day", "issue": "43", "normalized_date": "2020-10-19", "pages": "19254-19259", "proceedings_title": null, "publisher": "", "title": "Angewandte Chemie (International ed. in English)", "volume": "59", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Responsive Four-Coordinate Iron(II) Nodes in FePd(CN)(4).", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Cancer chemoresistance is often attributed to the presence of cancer stem cell (CSC)-like cells, but whether they are homogeneously chemoresistant remains unclear. We previously showed that in colon tumors, a subpopulation of LGR5(+) CSC-like cells driven by TCF1 (TCF7), a Wnt-responsive transcription factor, were responsible for tumorigenicity. Here we demonstrate that the tumorigenic subpopulation of mouse LGR5(+) cells exists in a slow-cycling state and identify a unique 22-gene signature that characterizes these slow-cycling CSC. Seven of the signature genes are specifically expressed in slow-cycling LGR5(+) cells from xenografted human colon tumors and are upregulated in colon cancer clinical specimens. Among these seven, four genes (APCDD1, NOTUM, PROX1, and SP5) are known to be direct Wnt target genes, and PROX1 was expressed in the invasive fronts of colon tumors. PROX1 was activated by TCF1 to induce CDKN1C and maintain a slow-cycling state in colon cancer organoids. Strikingly, PROX1 was required for recurrent growth after chemotherapeutic treatment, suggesting that inhibition of slow-cycling CSC by targeting the TCF1-PROX1-CDKN1C pathway is an effective strategy to combat refractory colon cancer in combination with conventional chemotherapy. SIGNIFICANCE: These findings illustrate the importance of a slow-cycling CSC subpopulation in colon cancer development and chemoresistance, with potential implications for the identified slow-cycling CSC signatures and the TCF1-PROX1-CDKN1C pathway as therapeutic targets.", "classifications": [ { "id": "Okamoto", "label": "Group Okamoto", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Daisuke", "last_name": "Shiokawa", "name": null }, { "creator_type": "author", "first_name": "Hiroaki", "last_name": "Sakai", "name": null }, { "creator_type": "author", "first_name": "Hirokazu", "last_name": "Ohata", "name": null }, { "creator_type": "author", "first_name": "Toshiaki", "last_name": "Miyazaki", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Kanda", "name": null }, { "creator_type": "author", "first_name": "Shigeki", "last_name": "Sekine", "name": null }, { "creator_type": "author", "first_name": "Daichi", "last_name": "Narushima", "name": null }, { "creator_type": "author", "first_name": "Masahito", "last_name": "Hosokawa", "name": null }, { "creator_type": "author", "first_name": "Mamoru", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Yutaka", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Haruko", "last_name": "Takeyama", "name": null }, { "creator_type": "author", "first_name": "Hideki", "last_name": "Kambara", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Nakagama", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Okamoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1158/0008-5472.can-20-0378" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "32816913" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Colonic Neoplasms", "descriptor_ui": "D003110", "major_topic": false }, { "descriptor": "Cyclin-Dependent Kinase Inhibitor p57", "descriptor_ui": "D050761", "major_topic": false }, { "descriptor": "Drug Resistance, Neoplasm", "descriptor_ui": "D019008", "major_topic": false }, { "descriptor": "Gene Expression Regulation, Neoplastic", "descriptor_ui": "D015972", "major_topic": false }, { "descriptor": "Homeodomain Proteins", "descriptor_ui": "D018398", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Neoplastic Stem Cells", "descriptor_ui": "D014411", "major_topic": false }, { "descriptor": "Prospero-Related Homeobox 1 Protein", "descriptor_ui": "D000098551", "major_topic": false }, { "descriptor": "Receptors, G-Protein-Coupled", "descriptor_ui": "D043562", "major_topic": false }, { "descriptor": "Sequence Analysis, RNA", "descriptor_ui": "D017423", "major_topic": false }, { "descriptor": "Single-Cell Analysis", "descriptor_ui": "D059010", "major_topic": false }, { "descriptor": "Spheroids, Cellular", "descriptor_ui": "D018874", "major_topic": false }, { "descriptor": "Tumor Suppressor Proteins", "descriptor_ui": "D025521", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020 Oct 15", "date_precision": "day", "issue": "20", "normalized_date": "2020-10-15", "pages": "4451-4464", "proceedings_title": null, "publisher": "", "title": "Cancer research", "volume": "80", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Slow-Cycling Cancer Stem Cells Regulate Progression and Chemoresistance in Colon Cancer.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Compositional analyses of eggs have primarily focused on nutritional components, including large molecules, such as proteins. However, few reports have investigated the effects of heating and hen feed crops on taste components, such as free amino acids and sugars. Herein, water-soluble metabolites in raw and boiled eggs produced from chickens raised with corn- or rice-fed were analyzed. Each egg was separated into yolk and white, and freeze-dried samples were analyzed by CE-MS and LC-MS. Abundant metabolites included amino acids in yolks and sugars in whites. Compared to corn-fed, rice-fed resulted in three times higher betaine and uridine monophosphate concentrations in yolks and whites, respectively. Boiled whites contained more than four times higher concentrations of amino acids and fructose than raw whites. Metabolites in yolks exhibited minimal changes after boiling. Our findings support the use of water-soluble metabolomics to evaluate the effects of heating and feed crops on taste components.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Tatsuki", "last_name": "Ogura", "name": null }, { "creator_type": "author", "first_name": "Masataka", "last_name": "Wakayama", "name": null }, { "creator_type": "author", "first_name": "Yujin", "last_name": "Ashino", "name": null }, { "creator_type": "author", "first_name": "Rie", "last_name": "Kadowaki", "name": null }, { "creator_type": "author", "first_name": "Miyu", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Masaru", "last_name": "Tomita", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.foodchem.2020.127077" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "32485660" } }, "mesh": [ { "descriptor": "Animal Feed", "descriptor_ui": "D000821", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Chickens", "descriptor_ui": "D002645", "major_topic": false }, { "descriptor": "Cooking", "descriptor_ui": "D003296", "major_topic": false }, { "descriptor": "Crops, Agricultural", "descriptor_ui": "D018556", "major_topic": true }, { "descriptor": "Egg White", "descriptor_ui": "D004529", "major_topic": true }, { "descriptor": "Egg Yolk", "descriptor_ui": "D004530", "major_topic": false }, { "descriptor": "Metabolome", "descriptor_ui": "D055442", "major_topic": false }, { "descriptor": "Oryza", "descriptor_ui": "D012275", "major_topic": true }, { "descriptor": "Zea mays", "descriptor_ui": "D003313", "major_topic": true } ], "publication": { "conference_name": null, "date": "2020 Oct 15", "date_precision": "day", "issue": "", "normalized_date": "2020-10-15", "pages": "127077", "proceedings_title": null, "publisher": "", "title": "Food chemistry", "volume": "327", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Effects of feed crops and boiling on chicken egg yolk and white determined by a metabolome analysis.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "PTBP1, a well-conserved RNA-binding protein, regulates cellular development by tuning posttranscriptional mRNA modification such as alternative splicing (AS) or mRNA stabilization. We previously revealed that the loss of Ptbp1 in spermatogonia causes the dysregulation of spermatogenesis, but the molecular mechanisms by which PTBP1 regulates spermatogonium homeostasis are unclear. In this study, changes of AS or transcriptome in Ptbp1-knockout (KO) germline stem cells (GSC), an in vitro model of proliferating spermatogonia, was determined by next generation sequencing. We identified more than 200 differentially expressed genes, as well as 85 genes with altered AS due to the loss of PTBP1. Surprisingly, no differentially expressed genes overlapped with different AS genes in Ptbp1-KO GSC. In addition, we observed that the mRNA expression of Nanos3, an essential gene for normal spermatogenesis, was significantly decreased in Ptbp1-KO spermatogonia. We also revealed that PTBP1 protein binds to Nanos3 mRNA in spermatogonia. Furthermore, Nanos3(+/-);Ptbp1(+/-) mice exhibited abnormal spermatogenesis, which resembled the effects of germ cell-specific Ptbp1 KO, whereas no significant abnormality was observed in mice heterozygous for either gene alone. These data implied that PTBP1 regulates alternative splicing and transcriptome in spermatogonia under different molecular pathways, and contributes spermatogenesis, at least in part, in concert with NANOS3.", "classifications": [ { "id": "Yamamoto", "label": "Group Yamamoto", "parent": "Toyoshima", "type": "group" }, { "id": "Toyoshima", "label": "Team Toyoshima", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Manami", "last_name": "Senoo", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Hozoji", "name": null }, { "creator_type": "author", "first_name": "Yu", "last_name": "Ishikawa-Yamauchi", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Takijiri", "name": null }, { "creator_type": "author", "first_name": "Sho", "last_name": "Ohta", "name": null }, { "creator_type": "author", "first_name": "Tomoyo", "last_name": "Ukai", "name": null }, { "creator_type": "author", "first_name": "Mio", "last_name": "Kabata", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Yasuhiro", "last_name": "Yamada", "name": null }, { "creator_type": "author", "first_name": "Masahito", "last_name": "Ikawa", "name": null }, { "creator_type": "author", "first_name": "Manabu", "last_name": "Ozawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1262/jrd.2020-060" }, "pmcid": { "normalized": "PMC7593632" }, "pmid": { "normalized": "32624547" } }, "mesh": [ { "descriptor": "Alternative Splicing", "descriptor_ui": "D017398", "major_topic": true }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Gene Deletion", "descriptor_ui": "D017353", "major_topic": false }, { "descriptor": "Gene Expression Regulation", "descriptor_ui": "D005786", "major_topic": true }, { "descriptor": "Genes, Regulator", "descriptor_ui": "D005809", "major_topic": false }, { "descriptor": "Germ Cells", "descriptor_ui": "D005854", "major_topic": false }, { "descriptor": "Heterozygote", "descriptor_ui": "D006579", "major_topic": false }, { "descriptor": "Infertility, Male", "descriptor_ui": "D007248", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Protein Tyrosine Phosphatase, Non-Receptor Type 1", "descriptor_ui": "D054562", "major_topic": false }, { "descriptor": "RNA-Binding Proteins", "descriptor_ui": "D016601", "major_topic": false }, { "descriptor": "RNA-Seq", "descriptor_ui": "D000081246", "major_topic": false }, { "descriptor": "Spermatogenesis", "descriptor_ui": "D013091", "major_topic": false }, { "descriptor": "Spermatogonia", "descriptor_ui": "D013093", "major_topic": false }, { "descriptor": "Testis", "descriptor_ui": "D013737", "major_topic": false }, { "descriptor": "Transcriptome", "descriptor_ui": "D059467", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020 Oct 13", "date_precision": "day", "issue": "5", "normalized_date": "2020-10-13", "pages": "459-467", "proceedings_title": null, "publisher": "", "title": "The Journal of reproduction and development", "volume": "66", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "RNA-binding protein Ptbp1 regulates alternative splicing and transcriptome in spermatogonia and maintains spermatogenesis in concert with Nanos3.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "An amendment to this paper has been published and can be accessed via a link at the top of the paper.", "classifications": [ { "id": "Fujita", "label": "Group Fujita", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yi-Shiou", "last_name": "Duh", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Nagasaki", "name": null }, { "creator_type": "author", "first_name": "Yu-Lung", "last_name": "Tang", "name": null }, { "creator_type": "author", "first_name": "Pang-Han", "last_name": "Wu", "name": null }, { "creator_type": "author", "first_name": "Hao-Yu", "last_name": "Cheng", "name": null }, { "creator_type": "author", "first_name": "Te-Hsin", "last_name": "Yen", "name": null }, { "creator_type": "author", "first_name": "Hou-Xian", "last_name": "Ding", "name": null }, { "creator_type": "author", "first_name": "Kentaro", "last_name": "Nishida", "name": null }, { "creator_type": "author", "first_name": "Ikuto", "last_name": "Hotta", "name": null }, { "creator_type": "author", "first_name": "Jhen-Hong", "last_name": "Yang", "name": null }, { "creator_type": "author", "first_name": "Yu-Ping", "last_name": "Lo", "name": null }, { "creator_type": "author", "first_name": "Kuo-Ping", "last_name": "Chen", "name": null }, { "creator_type": "author", "first_name": "Katsumasa", "last_name": "Fujita", "name": null }, { "creator_type": "author", "first_name": "Chih-Wei", "last_name": "Chang", "name": null }, { "creator_type": "author", "first_name": "Kung-Hsuan", "last_name": "Lin", "name": null }, { "creator_type": "author", "first_name": "Junichi", "last_name": "Takahara", "name": null }, { "creator_type": "author", "first_name": "Shi-Wei", "last_name": "Chu", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41467-020-19073-5" }, "pmcid": { "normalized": "PMC7541503" }, "pmid": { "normalized": "33028831" } }, "mesh": [], "publication": { "conference_name": null, "date": "2020 Oct 7", "date_precision": "day", "issue": "1", "normalized_date": "2020-10-07", "pages": "5136", "proceedings_title": null, "publisher": "", "title": "Nature communications", "volume": "11", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Publisher Correction: Giant photothermal nonlinearity in a single silicon nanostructure.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "We report the dynamics of lipid droplet formation induced by introducing cis- and/or trans-fatty acids into cells. Raman imaging allows the chemical analysis of each droplet, showing that exogenous fatty acids initially enter original endogenous droplets, then induce additional droplets containing endogenous lipids, and finally form their droplets.", "classifications": [ { "id": "Nakabayashi", "label": "Group Nakabayashi", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Hiroaki", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Aya", "last_name": "Yanamisawa", "name": null }, { "creator_type": "author", "first_name": "Shinji", "last_name": "Kajimoto", "name": null }, { "creator_type": "author", "first_name": "Takakazu", "last_name": "Nakabayashi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1039/d0cp03805a" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "32985622" } }, "mesh": [ { "descriptor": "Fatty Acids", "descriptor_ui": "D005227", "major_topic": false }, { "descriptor": "HeLa Cells", "descriptor_ui": "D006367", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Lipid Droplets", "descriptor_ui": "D066292", "major_topic": false }, { "descriptor": "Microscopy", "descriptor_ui": "D008853", "major_topic": true }, { "descriptor": "Spectrum Analysis, Raman", "descriptor_ui": "D013059", "major_topic": true } ], "publication": { "conference_name": null, "date": "2020 Oct 7", "date_precision": "day", "issue": "38", "normalized_date": "2020-10-07", "pages": "21646-21650", "proceedings_title": null, "publisher": "", "title": "Physical chemistry chemical physics : PCCP", "volume": "22", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Observation of the changes in the chemical composition of lipid droplets using Raman microscopy.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Regulatory mechanisms of germline differentiation have generally been explained via the function of signaling pathways, transcription factors, and epigenetic regulation; however, little is known regarding proteomic and metabolomic regulation and their contribution to germ cell development. Here, we conducted integrated proteomic and metabolomic analyses of fetal germ cells in mice on embryonic day (E)13.5 and E18.5 and demonstrate sex- and developmental stage-dependent changes in these processes. In male germ cells, RNA processing, translation, oxidative phosphorylation, and nucleotide synthesis are dominant in E13.5 and then decline until E18.5, which corresponds to the prolonged cell division and more enhanced hyper-transcription/translation in male primordial germ cells and their subsequent repression. Tricarboxylic acid cycle and one-carbon pathway are consistently upregulated in fetal male germ cells, suggesting their involvement in epigenetic changes preceding in males. Increased protein stability and oxidative phosphorylation during female germ cell differentiation suggests an upregulation of aerobic energy metabolism, which likely contributes to the proteostasis required for oocyte maturation in subsequent stages. The features elucidated in this study shed light on the unrevealed mechanisms of germ cell development.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yohei", "last_name": "Hayashi", "name": null }, { "creator_type": "author", "first_name": "Masaru", "last_name": "Mori", "name": null }, { "creator_type": "author", "first_name": "Kaori", "last_name": "Igarashi", "name": null }, { "creator_type": "author", "first_name": "Keiko", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Asuka", "last_name": "Takehara", "name": null }, { "creator_type": "author", "first_name": "Yumi", "last_name": "Ito-Matsuoka", "name": null }, { "creator_type": "author", "first_name": "Akio", "last_name": "Kanai", "name": null }, { "creator_type": "author", "first_name": "Nobuo", "last_name": "Yaegashi", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Yasuhisa", "last_name": "Matsui", "name": null } ], "identifiers": { "doi": { "normalized": "10.1093/biolre/ioaa115" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "32627815" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "DNA", "descriptor_ui": "D004247", "major_topic": false }, { "descriptor": "DNA Methylation", "descriptor_ui": "D019175", "major_topic": false }, { "descriptor": "Embryo, Mammalian", "descriptor_ui": "D004622", "major_topic": false }, { "descriptor": "Embryonic Germ Cells", "descriptor_ui": "D000066473", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Gene Expression Regulation, Developmental", "descriptor_ui": "D018507", "major_topic": false }, { "descriptor": "Genome-Wide Association Study", "descriptor_ui": "D055106", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Metabolomics", "descriptor_ui": "D055432", "major_topic": true }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Transgenic", "descriptor_ui": "D008822", "major_topic": false }, { "descriptor": "Proteomics", "descriptor_ui": "D040901", "major_topic": true }, { "descriptor": "Sex Differentiation", "descriptor_ui": "D012733", "major_topic": false }, { "descriptor": "Sex Factors", "descriptor_ui": "D012737", "major_topic": false }, { "descriptor": "Transcription Factors", "descriptor_ui": "D014157", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020 Oct 5", "date_precision": "day", "issue": "4", "normalized_date": "2020-10-05", "pages": "717-735", "proceedings_title": null, "publisher": "", "title": "Biology of reproduction", "volume": "103", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Proteomic and metabolomic analyses uncover sex-specific regulatory pathways in mouse fetal germline differentiationdagger.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Testicular germ cell tumor (GCT) is the most common type of malignancy in young males. Patients with nonseminomatous GCT still have poor prognosis. To identify new therapeutic targets, we generated patient-derived cells (PDCs) and their xenograft (PDCX) models from 3 distinct GCT patients' specimens. The pathological features of GCT PDCs and PDCX tumors recapitulated those of nonseminomatous components exhibiting in the corresponding patients' specimens. Notably, stemness-related markers and hypoxia-related genes, including hypoxia inducible factor 1alpha (HIF1A) and neuritin 1 (NRN1), were abundantly expressed in three-dimensional spheroid cultures of GCT PDCs. We identified functional HIF1alpha response elements in the NRN1 promoter and defined that their transcriptional activities were substantially activated by hypoxia. HIF1alpha inhibition by siRNAs or an inhibitor, 2-methoxyestradiol, significantly suppressed NRN1 expression and decreased the in vitro and in vivo growth of PDC spheroids. Moreover, NRN1 knockdown efficiently suppressed PDC proliferation. These results suggest that HIF1alpha and NRN1 are potential diagnostic and therapeutic targets, and that 2-methoxyestradiol could be applied to clinical management of GCT. Overall, our GCT PDC and PDCX models would be useful as preclinical models for precision medicine targeting each patient.", "classifications": [ { "id": "Okamoto", "label": "Group Okamoto", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Takeshi", "last_name": "Namekawa", "name": null }, { "creator_type": "author", "first_name": "Sachi", "last_name": "Kitayama", "name": null }, { "creator_type": "author", "first_name": "Kazuhiro", "last_name": "Ikeda", "name": null }, { "creator_type": "author", "first_name": "Kuniko", "last_name": "Horie-Inoue", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Okamoto", "name": null }, { "creator_type": "author", "first_name": "Tomohiko", "last_name": "Ichikawa", "name": null }, { "creator_type": "author", "first_name": "Akihiro", "last_name": "Yano", "name": null }, { "creator_type": "author", "first_name": "Satoru", "last_name": "Kawakami", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Inoue", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.canlet.2020.05.040" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "32544513" } }, "mesh": [ { "descriptor": "2-Methoxyestradiol", "descriptor_ui": "D000077584", "major_topic": false }, { "descriptor": "Antineoplastic Agents", "descriptor_ui": "D000970", "major_topic": false }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Cell Proliferation", "descriptor_ui": "D049109", "major_topic": false }, { "descriptor": "GPI-Linked Proteins", "descriptor_ui": "D058851", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Hypoxia-Inducible Factor 1, alpha Subunit", "descriptor_ui": "D051795", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Neoplasms, Germ Cell and Embryonal", "descriptor_ui": "D009373", "major_topic": false }, { "descriptor": "Neuropeptides", "descriptor_ui": "D009479", "major_topic": false }, { "descriptor": "Spheroids, Cellular", "descriptor_ui": "D018874", "major_topic": false }, { "descriptor": "Testicular Neoplasms", "descriptor_ui": "D013736", "major_topic": false }, { "descriptor": "Xenograft Model Antitumor Assays", "descriptor_ui": "D023041", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020 Oct 1", "date_precision": "day", "issue": "", "normalized_date": "2020-10-01", "pages": "79-86", "proceedings_title": null, "publisher": "", "title": "Cancer letters", "volume": "489", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "HIF1alpha inhibitor 2-methoxyestradiol decreases NRN1 expression and represses in vivo and in vitro growth of patient-derived testicular germ cell tumor spheroids.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "We developed a new system that causes specific degradation of type II arabinogalactans by dexamethasone-inducible expression of a fungal exo-β-1,3-galactanase in Arabidopsis, producing severe tissue disorganization in the hypocotyl and cotyledons.", "classifications": [ { "id": "Higaki", "label": "Group Higaki", "parent": "Ueda", "type": "group" }, { "id": "Ueda", "label": "Team Ueda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yoshihisa", "last_name": "Yoshimi", "name": null }, { "creator_type": "author", "first_name": "Katsuya", "last_name": "Hara", "name": null }, { "creator_type": "author", "first_name": "Mami", "last_name": "Yoshimura", "name": null }, { "creator_type": "author", "first_name": "Nobukazu", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Takumi", "last_name": "Higaki", "name": null }, { "creator_type": "author", "first_name": "Yoichi", "last_name": "Tsumuraya", "name": null }, { "creator_type": "author", "first_name": "Toshihisa", "last_name": "Kotake", "name": null } ], "identifiers": { "doi": { "normalized": "10.1093/jxb/eraa236" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "32470141" } }, "mesh": [ { "descriptor": "Arabidopsis", "descriptor_ui": "D017360", "major_topic": true }, { "descriptor": "Cell Shape", "descriptor_ui": "D048430", "major_topic": false }, { "descriptor": "Galactans", "descriptor_ui": "D005685", "major_topic": false }, { "descriptor": "Mucoproteins", "descriptor_ui": "D009088", "major_topic": false }, { "descriptor": "Oligosaccharides", "descriptor_ui": "D009844", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020 Sep 19", "date_precision": "day", "issue": "18", "normalized_date": "2020-09-19", "pages": "5414-5424", "proceedings_title": null, "publisher": "", "title": "Journal of Experimental Botany", "volume": "71", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Expression of a fungal exo-β-1,3-galactanase in Arabidopsis reveals a role of type II arabinogalactans in the regulation of cell shape.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Adipose tissue is essential for metabolic homeostasis, balancing lipid storage and mobilization based on nutritional status. This is coordinated by insulin, which triggers kinase signaling cascades to modulate numerous metabolic proteins, leading to increased glucose uptake and anabolic processes like lipogenesis. Given recent evidence that glucose is dispensable for adipocyte respiration, we sought to test whether glucose is necessary for insulin-stimulated anabolism. Examining lipogenesis in cultured adipocytes, glucose was essential for insulin to stimulate the synthesis of fatty acids and glyceride-glycerol. Importantly, glucose was dispensable for lipogenesis in the absence of insulin, suggesting that distinct carbon sources are used with or without insulin. Metabolic tracing studies revealed that glucose was required for insulin to stimulate pathways providing carbon substrate, NADPH, and glycerol 3-phosphate for lipid synthesis and storage. Glucose also displaced leucine as a lipogenic substrate and was necessary to suppress fatty acid oxidation. Together, glucose provided substrates and metabolic control for insulin to promote lipogenesis in adipocytes. This contrasted with the suppression of lipolysis by insulin signaling, which occurred independently of glucose. Given previous observations that signal transduction acts primarily before glucose uptake in adipocytes, these data are consistent with a model whereby insulin initially utilizes protein phosphorylation to stimulate lipid anabolism, which is sustained by subsequent glucose metabolism. Consequently, lipid abundance was sensitive to glucose availability, both during adipogenesis and in Drosophila flies in vivo Together, these data highlight the importance of glucose metabolism to support insulin action, providing a complementary regulatory mechanism to signal transduction to stimulate adipose anabolism.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "James R.", "last_name": "Krycer", "name": null }, { "creator_type": "author", "first_name": "Lake-Ee", "last_name": "Quek", "name": null }, { "creator_type": "author", "first_name": "Deanne", "last_name": "Francis", "name": null }, { "creator_type": "author", "first_name": "Armella", "last_name": "Zadoorian", "name": null }, { "creator_type": "author", "first_name": "Fiona C.", "last_name": "Weiss", "name": null }, { "creator_type": "author", "first_name": "Kristen C.", "last_name": "Cooke", "name": null }, { "creator_type": "author", "first_name": "Marin E.", "last_name": "Nelson", "name": null }, { "creator_type": "author", "first_name": "Alexis", "last_name": "Diaz-Vegas", "name": null }, { "creator_type": "author", "first_name": "Sean J.", "last_name": "Humphrey", "name": null }, { "creator_type": "author", "first_name": "Richard", "last_name": "Scalzo", "name": null }, { "creator_type": "author", "first_name": "Akiyoshi", "last_name": "Hirayama", "name": null }, { "creator_type": "author", "first_name": "Satsuki", "last_name": "Ikeda", "name": null }, { "creator_type": "author", "first_name": "Futaba", "last_name": "Shoji", "name": null }, { "creator_type": "author", "first_name": "Kumi", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Kevin", "last_name": "Huynh", "name": null }, { "creator_type": "author", "first_name": "Corey", "last_name": "Giles", "name": null }, { "creator_type": "author", "first_name": "Bianca", "last_name": "Varney", "name": null }, { "creator_type": "author", "first_name": "Shilpa R.", "last_name": "Nagarajan", "name": null }, { "creator_type": "author", "first_name": "Andrew J.", "last_name": "Hoy", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Peter J.", "last_name": "Meikle", "name": null }, { "creator_type": "author", "first_name": "Gregory J.", "last_name": "Cooney", "name": null }, { "creator_type": "author", "first_name": "Daniel J.", "last_name": "Fazakerley", "name": null }, { "creator_type": "author", "first_name": "David E.", "last_name": "James", "name": null } ], "identifiers": { "doi": { "normalized": "10.1074/jbc.ra120.014907" }, "pmcid": { "normalized": "PMC7504926" }, "pmid": { "normalized": "32723868" } }, "mesh": [ { "descriptor": "3T3-L1 Cells", "descriptor_ui": "D041721", "major_topic": false }, { "descriptor": "Adipocytes", "descriptor_ui": "D017667", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Drosophila melanogaster", "descriptor_ui": "D004331", "major_topic": false }, { "descriptor": "Drosophila Proteins", "descriptor_ui": "D029721", "major_topic": false }, { "descriptor": "Glucose", "descriptor_ui": "D005947", "major_topic": false }, { "descriptor": "Glycerophosphates", "descriptor_ui": "D005994", "major_topic": false }, { "descriptor": "Insulin", "descriptor_ui": "D007328", "major_topic": false }, { "descriptor": "Lipogenesis", "descriptor_ui": "D050155", "major_topic": true }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "NADP", "descriptor_ui": "D009249", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": true } ], "publication": { "conference_name": null, "date": "2020 Sep 18", "date_precision": "day", "issue": "38", "normalized_date": "2020-09-18", "pages": "13250-13266", "proceedings_title": null, "publisher": "", "title": "The Journal of biological chemistry", "volume": "295", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Insulin signaling requires glucose to promote lipid anabolism in adipocytes.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The unprecedented synthesis of gem-difluoroalkenes through the Ramberg-Backlund reaction of alkyl triflones is described herein. Structurally diverse, fully substituted gem-difluoroalkenes that are difficult to prepare by other methods can be easily prepared from readily available triflones by treatment with specific Grignard reagents. Experimental and computational studies provide insight into the unique and critical role of the Grignard reagent, which serves both as a base to remove the alpha-proton and as a Lewis acid to assist C-F bond activation.", "classifications": [ { "id": "Nanbo", "label": "Group Nanbo", "parent": "Tsuchiya", "type": "group" }, { "id": "Tsuchiya", "label": "Team Tsuchiya", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yuuki", "last_name": "Maekawa", "name": null }, { "creator_type": "author", "first_name": "Masakazu", "last_name": "Nambo", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Yokogawa", "name": null }, { "creator_type": "author", "first_name": "Cathleen M.", "last_name": "Crudden", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/jacs.0c07924" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "32799441" } }, "mesh": [], "publication": { "conference_name": null, "date": "2020 Sep 16", "date_precision": "day", "issue": "37", "normalized_date": "2020-09-16", "pages": "15667-15672", "proceedings_title": null, "publisher": "", "title": "Journal of the American Chemical Society", "volume": "142", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Alkyltriflones in the Ramberg-Backlund Reaction: An Efficient and Modular Synthesis of gem-Difluoroalkenes.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "PURPOSE: To determine a correlation between temperature and blood flow in the ocular anterior segment, and their effects on corneal temperature. METHODS: In experiment 1, we recruited 40 eyes and measured the temperature and blood flow in the ocular anterior-segment (upper/lower eyelid skin, palpebral and bulbar conjunctiva, and cornea) before and after application of warm compresses. In experiment 2, we recruited 20 eyes and measured the same tissues before and during stimulation using water and capsaicin solution in the oral cavity. RESULTS: In experiment 1, the temperatures of the upper/lower eyelid skin and cornea increased significantly until 15 min after the application of the warm compress; the temperatures of the palpebral and bulbar conjunctiva increased significantly until 10 min. The blood flow in the upper/lower eyelid skin and bulbar conjunctiva increased significantly until 10 min, and that of the palpebral conjunctiva increased significantly until 15 min. In experiment 2, the temperatures were correlated significantly with the blood flow in the upper and lower eyelid skin and palpebral and bulbar conjunctiva. The temperature of all locations and palpebral conjunctival blood flow contributed independently to the corneal temperature. CONCLUSIONS: In the ocular anterior segment, the temperature and blood flow were correlated significantly, and contributed to the corneal temperature.", "classifications": [ { "id": "Suzuki", "label": "Group Suzuki", "parent": "Takekawa", "type": "group" }, { "id": "Takekawa", "label": "Team Takekawa", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Takashi", "last_name": "Itokawa", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Yukinobu", "last_name": "Okajima", "name": null }, { "creator_type": "author", "first_name": "Tatsuhiko", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Hiroko", "last_name": "Iwashita", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Gotoda", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Kakisu", "name": null }, { "creator_type": "author", "first_name": "Yuto", "last_name": "Tei", "name": null }, { "creator_type": "author", "first_name": "Yuichi", "last_name": "Hori", "name": null } ], "identifiers": { "doi": { "normalized": "10.3390/diagnostics10090695" }, "pmcid": { "normalized": "PMC7554717" }, "pmid": { "normalized": "32942653" } }, "mesh": [], "publication": { "conference_name": null, "date": "2020 Sep 15", "date_precision": "day", "issue": "9", "normalized_date": "2020-09-15", "pages": "", "proceedings_title": null, "publisher": "", "title": "Diagnostics (Basel, Switzerland)", "volume": "10", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Correlation between Blood Flow and Temperature of the Ocular Anterior Segment in Normal Subjects.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Recent advances in cancer biology reveal the importance of metabolic changes in cancer; however, less is known about how metabolic pathways in tumors are regulated in vivo. Here, we report analysis of the lung cancer metabolism based on different surgical procedures, namely lobectomy and partial resection. In lobectomy, but not in partial resection, pulmonary arteries and veins are ligated prior to removal of tissues, rendering tissues ischemic. We show that tumors indeed undergo ischemia upon lobectomy and that the tumor metabolome differs markedly from that of tumors removed by partial resection. Comparison of the responses to ischemia in tumor and normal lung tissues revealed that lung cancer tissue exhibits greater TCA cycle and autophagic activity than do normal lung tissues in vivo in patients. Finally, we report that deleting ATG7, which encodes a protein essential for autophagy, antagonizes growth of tumors derived from lung cancer cell lines, suggesting that autophagy confers metabolic advantages to lung cancer. Our findings shed light on divergent metabolic responses to ischemia seen in tumors and normal tissues.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Naohiko", "last_name": "Kikuchi", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Miyuki", "last_name": "Nomura", "name": null }, { "creator_type": "author", "first_name": "Taku", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Yoshimi", "last_name": "Sakamoto", "name": null }, { "creator_type": "author", "first_name": "Ryota", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Jiro", "last_name": "Abe", "name": null }, { "creator_type": "author", "first_name": "Mami", "last_name": "Morita", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Shima", "name": null }, { "creator_type": "author", "first_name": "Yoshinori", "last_name": "Okada", "name": null }, { "creator_type": "author", "first_name": "Nobuhiro", "last_name": "Tanuma", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.bbrc.2020.07.082" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "32828300" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Autophagy", "descriptor_ui": "D001343", "major_topic": false }, { "descriptor": "Autophagy-Related Protein 7", "descriptor_ui": "D000071193", "major_topic": false }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Citric Acid Cycle", "descriptor_ui": "D002952", "major_topic": true }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Gene Deletion", "descriptor_ui": "D017353", "major_topic": false }, { "descriptor": "Ischemia", "descriptor_ui": "D007511", "major_topic": false }, { "descriptor": "Lung Neoplasms", "descriptor_ui": "D008175", "major_topic": false }, { "descriptor": "Metabolome", "descriptor_ui": "D055442", "major_topic": true }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020 Sep 10", "date_precision": "day", "issue": "1", "normalized_date": "2020-09-10", "pages": "285-291", "proceedings_title": null, "publisher": "", "title": "Biochemical and biophysical research communications", "volume": "530", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Comparison of the ischemic and non-ischemic lung cancer metabolome reveals hyper activity of the TCA cycle and autophagy.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Cell-to-cell variability in signal transduction in biological systems is often considered noise. However, intercellular variation (i.e., cell-to-cell variability) has the potential to enable individual cells to encode different information. Here, we show that intercellular variation increases information transmission of skeletal muscle. We analyze the responses of multiple cultured myotubes or isolated skeletal muscle fibers as a multiple-cell channel composed of single-cell channels. We find that the multiple-cell channel, which incorporates intercellular variation as information, not noise, transmitted more information in the presence of intercellular variation than in the absence according to the \"response diversity effect,\" increasing in the gradualness of dose response by summing the cell-to-cell variable dose responses. We quantify the information transmission of human facial muscle contraction during intraoperative neurophysiological monitoring and find that information transmission of muscle contraction is comparable to that of a multiple-cell channel. Thus, our data indicate that intercellular variation can increase the information capacity of tissues.", "classifications": [ { "id": "Kuroda", "label": "Group Kuroda", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Takumi", "last_name": "Wada", "name": null }, { "creator_type": "author", "first_name": "Ken-Ichi", "last_name": "Hironaka", "name": null }, { "creator_type": "author", "first_name": "Mitsutaka", "last_name": "Wataya", "name": null }, { "creator_type": "author", "first_name": "Masashi", "last_name": "Fujii", "name": null }, { "creator_type": "author", "first_name": "Miki", "last_name": "Eto", "name": null }, { "creator_type": "author", "first_name": "Shinsuke", "last_name": "Uda", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Hoshino", "name": null }, { "creator_type": "author", "first_name": "Katsuyuki", "last_name": "Kunida", "name": null }, { "creator_type": "author", "first_name": "Haruki", "last_name": "Inoue", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Kubota", "name": null }, { "creator_type": "author", "first_name": "Tsuguto", "last_name": "Takizawa", "name": null }, { "creator_type": "author", "first_name": "Yasuaki", "last_name": "Karasawa", "name": null }, { "creator_type": "author", "first_name": "Hirofumi", "last_name": "Nakatomi", "name": null }, { "creator_type": "author", "first_name": "Nobuhito", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Hiroki", "last_name": "Hamaguchi", "name": null }, { "creator_type": "author", "first_name": "Yasuro", "last_name": "Furuichi", "name": null }, { "creator_type": "author", "first_name": "Yasuko", "last_name": "Manabe", "name": null }, { "creator_type": "author", "first_name": "Nobuharu L.", "last_name": "Fujii", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Kuroda", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.celrep.2020.108051" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "32877665" } }, "mesh": [ { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Muscle, Skeletal", "descriptor_ui": "D018482", "major_topic": false }, { "descriptor": "Single-Cell Analysis", "descriptor_ui": "D059010", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020 Sep 1", "date_precision": "day", "issue": "9", "normalized_date": "2020-09-01", "pages": "108051", "proceedings_title": null, "publisher": "", "title": "Cell reports", "volume": "32", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Single-Cell Information Analysis Reveals That Skeletal Muscles Incorporate Cell-to-Cell Variability as Information Not Noise.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Several challenges appear in the application of deep learning to genomic data. First, the dimensionality of input can be orders of magnitude greater than the number of samples, forcing the model to be prone to overfitting the training dataset. Second, each input variable's contribution to the prediction is usually difficult to interpret, owing to multiple nonlinear operations. Third, genetic data features sometimes have no innate structure. To alleviate these problems, we propose a modification to Diet Networks by adding element-wise input scaling. The original Diet Networks concept can considerably reduce the number of parameters of the fully-connected layers by taking the transposed data matrix as an input to its auxiliary network. The efficacy of the proposed architecture was evaluated on a binary classification task for lung cancer histology, that is, adenocarcinoma or squamous cell carcinoma, from a somatic mutation profile. The dataset consisted of 950 cases, and 5-fold cross-validation was performed for evaluating the model performance. The model achieved a prediction accuracy of around 80% and showed that our modification markedly stabilized the learning process. Also, latent representations acquired inside the model allowed us to interpret the relationship between somatic mutation sites for the prediction.", "classifications": [ { "id": "Hamamoto", "label": "Group Hamamoto", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Kazuma", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Amina", "last_name": "Bolatkan", "name": null }, { "creator_type": "author", "first_name": "Shuichiro", "last_name": "Shiina", "name": null }, { "creator_type": "author", "first_name": "Ryuji", "last_name": "Hamamoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.3390/biom10091249" }, "pmcid": { "normalized": "PMC7563438" }, "pmid": { "normalized": "32872133" } }, "mesh": [ { "descriptor": "Adenocarcinoma", "descriptor_ui": "D000230", "major_topic": false }, { "descriptor": "Carcinoma, Squamous Cell", "descriptor_ui": "D002294", "major_topic": false }, { "descriptor": "Diagnosis, Computer-Assisted", "descriptor_ui": "D003936", "major_topic": true }, { "descriptor": "Diagnosis, Differential", "descriptor_ui": "D003937", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Lung Neoplasms", "descriptor_ui": "D008175", "major_topic": false }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": false }, { "descriptor": "Neural Networks, Computer", "descriptor_ui": "D016571", "major_topic": true }, { "descriptor": "Reproducibility of Results", "descriptor_ui": "D015203", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020 Aug 28", "date_precision": "day", "issue": "9", "normalized_date": "2020-08-28", "pages": "", "proceedings_title": null, "publisher": "", "title": "Biomolecules", "volume": "10", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Fully-Connected Neural Networks with Reduced Parameterization for Predicting Histological Types of Lung Cancer from Somatic Mutations.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "A fluorophore encapsulated in a metal-organic framework showed photochromic multicolour fluorescence. Irradiation with an ultraviolet laser induced the relocation of the fluorophore from a polar to a nonpolar environment, altering the emission from red to blue. This change in emission color can be repeatably recovered by heating the fluorophore-MOF composite.", "classifications": [ { "id": "Hijikata", "label": "Group Hijikata", "parent": "Tsuchiya", "type": "group" }, { "id": "Tsuchiya", "label": "Team Tsuchiya", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Kenji", "last_name": "Hirai", "name": null }, { "creator_type": "author", "first_name": "Taisei", "last_name": "Kitagawa", "name": null }, { "creator_type": "author", "first_name": "Hideki", "last_name": "Fujiwara", "name": null }, { "creator_type": "author", "first_name": "Jenny", "last_name": "Pirillo", "name": null }, { "creator_type": "author", "first_name": "Yuh", "last_name": "Hijikata", "name": null }, { "creator_type": "author", "first_name": "Tomoko", "last_name": "Inose", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Uji-I", "name": null } ], "identifiers": { "doi": { "normalized": "10.1039/d0cc03624b" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "32692334" } }, "mesh": [ { "descriptor": "Color", "descriptor_ui": "D003116", "major_topic": false }, { "descriptor": "Fluorescent Dyes", "descriptor_ui": "D005456", "major_topic": false }, { "descriptor": "Metal-Organic Frameworks", "descriptor_ui": "D000073396", "major_topic": false }, { "descriptor": "Spectrum Analysis, Raman", "descriptor_ui": "D013059", "major_topic": false }, { "descriptor": "Ultraviolet Rays", "descriptor_ui": "D014466", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020 Aug 28", "date_precision": "day", "issue": "67", "normalized_date": "2020-08-28", "pages": "9651-9654", "proceedings_title": null, "publisher": "", "title": "Chemical communications (Cambridge, England)", "volume": "56", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Multicolour photochromic fluorescence of a fluorophore encapsulated in a metal-organic framework.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Light-inducible gene expression systems represent powerful methods for studying the functional roles of dynamic gene expression. Here, we developed an optimized light-inducible Gal4/UAS gene expression system for mammalian cells. We designed photoactivatable (PA)-Gal4 transcriptional activators based on the concept of split transcription factors, in which light-dependent interactions between Cry2-CIB1 PA-protein interaction modules can reconstitute a split Gal4 DNA-binding domain and p65 transcription activation domain. We developed a set of PA-Gal4 transcriptional activators (PA-Gal4cc), which differ in terms of induced gene expression levels following pulsed or prolonged light exposure, and which have different activation/deactivation kinetics. These systems offer optogenetic tools for the precise manipulation of gene expression at fine spatiotemporal resolution in mammalian cells.", "classifications": [ { "id": "JPMJCR1921", "label": "JPMJCR1921", "researcher": "Itaru Imayoshi", "type": "grant" }, { "id": "Imayoshi", "label": "Group Imayoshi", "parent": "Imayoshi", "type": "group" }, { "id": "Imayoshi", "label": "Team Imayoshi", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Mayumi", "last_name": "Yamada", "name": null }, { "creator_type": "author", "first_name": "Shinji C.", "last_name": "Nagasaki", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Yukinori", "last_name": "Hirano", "name": null }, { "creator_type": "author", "first_name": "Itaru", "last_name": "Imayoshi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.isci.2020.101506" }, "pmcid": { "normalized": "PMC7491154" }, "pmid": { "normalized": "32919371" } }, "mesh": [], "publication": { "conference_name": null, "date": "2020 Aug 27", "date_precision": "day", "issue": "9", "normalized_date": "2020-08-27", "pages": "101506", "proceedings_title": null, "publisher": "", "title": "iScience", "volume": "23", "year": 2020 }, "ssbd": { "database": [ "ssbd-database-000229" ], "repository": [ "ssbd-repos-000229" ] }, "title": "Optimization of Light-Inducible Gal4/UAS Gene Expression System in Mammalian Cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "CRISPR/Cas-mediated genome editing is a powerful tool for generating genetically mutated cells and organisms. Linearisation of donor cassettes with this system has been shown to facilitate both transgene donor insertion and targeted knock-in. Here, we developed a donor plasmid that we name pCriMGET (plasmid of synthetic CRISPR coded RNA target sequence-equipped donor plasmid-mediated gene targeting), in which an off-target free synthetic CRISPR coded RNA-target sequence (syn-crRNA-TS) is incorporated with a multi-cloning site, where a donor cassette can be inserted. With co-expression of Cas9 and the syn-crRNA-TS guide RNA (gRNA), pCriMGET provides a linearised donor cassette in vivo, thereby promoting the transgene donor insertion and targeted knock-in. When co-injected with Cas9 protein and gRNA into murine zygotes, pCriMGET yielded around 20% transgene insertion in embryos. This method also achieved more than 25% in-frame knock-in at the mouse Tbx3 gene locus without predicted insertion-deletion mutations using a transgene donor with 400-bp homology arms. pCriMGET is therefore useful as a versatile CRISPR/Cas9-cleavable donor plasmid for efficient integration and targeted knock-in of exogenous DNA in mice.", "classifications": [ { "id": "Toyoshima", "label": "Group Toyoshima", "parent": "Toyoshima", "type": "group" }, { "id": "Toyoshima", "label": "Team Toyoshima", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Riki", "last_name": "Ishibashi", "name": null }, { "creator_type": "author", "first_name": "Kota", "last_name": "Abe", "name": null }, { "creator_type": "author", "first_name": "Nanami", "last_name": "Ido", "name": null }, { "creator_type": "author", "first_name": "Satsuki", "last_name": "Kitano", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Miyachi", "name": null }, { "creator_type": "author", "first_name": "Fumiko", "last_name": "Toyoshima", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41598-020-70804-6" }, "pmcid": { "normalized": "PMC7445171" }, "pmid": { "normalized": "32839482" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "CRISPR-Cas Systems", "descriptor_ui": "D064113", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Gene Editing", "descriptor_ui": "D000072669", "major_topic": false }, { "descriptor": "Gene Knock-In Techniques", "descriptor_ui": "D055879", "major_topic": false }, { "descriptor": "Gene Targeting", "descriptor_ui": "D018390", "major_topic": false }, { "descriptor": "Genetic Engineering", "descriptor_ui": "D005818", "major_topic": false }, { "descriptor": "Genome", "descriptor_ui": "D016678", "major_topic": false }, { "descriptor": "HEK293 Cells", "descriptor_ui": "D057809", "major_topic": false }, { "descriptor": "HeLa Cells", "descriptor_ui": "D006367", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "INDEL Mutation", "descriptor_ui": "D054643", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Inbred ICR", "descriptor_ui": "D008813", "major_topic": false }, { "descriptor": "Mice, Transgenic", "descriptor_ui": "D008822", "major_topic": false }, { "descriptor": "Plasmids", "descriptor_ui": "D010957", "major_topic": false }, { "descriptor": "RNA, Guide, CRISPR-Cas Systems", "descriptor_ui": "D000094704", "major_topic": false }, { "descriptor": "T-Box Domain Proteins", "descriptor_ui": "D020825", "major_topic": false }, { "descriptor": "Transgenes", "descriptor_ui": "D019076", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020 Aug 24", "date_precision": "day", "issue": "1", "normalized_date": "2020-08-24", "pages": "14120", "proceedings_title": null, "publisher": "", "title": "Scientific reports", "volume": "10", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Genome editing with the donor plasmid equipped with synthetic crRNA-target sequence.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Tissue absorbance, light scattering, and autofluorescence are significantly lower in the near-infrared (NIR) range than in the visible range. Because of these advantages, NIR fluorescent proteins (FPs) are in high demand for in vivo imaging. Nevertheless, application of NIR FPs such as iRFP is still limited due to their dimness in mammalian cells. In contrast to GFP and its variants, iRFP requires biliverdin (BV) as a chromophore. The dimness of iRFP is at least partly due to rapid reduction of BV by biliverdin reductase-A (BLVRA). Here, we established biliverdin reductase-a knockout (Blvra(-/-)) mice to increase the intracellular BV concentration and, thereby, to enhance iRFP fluorescence intensity. As anticipated, iRFP fluorescence intensity was significantly increased in all examined tissues of Blvra(-/-) mice. Similarly, the genetically encoded calcium indicator NIR-GECO1, which is engineered based on another NIR FP, mIFP, exhibited a marked increase in fluorescence intensity in mouse embryonic fibroblasts derived from Blvra(-/-) mice. We expanded this approach to an NIR light-sensing optogenetic tool, the BphP1-PpsR2 system, which also requires BV as a chromophore. Again, deletion of the Blvra gene markedly enhanced the light response in HeLa cells. These results indicate that the Blvra(-/-) mouse is a versatile tool for the in vivo application of NIR FPs and NIR light-sensing optogenetic tools.Key words: in vivo imaging, near-infrared fluorescent protein, biliverdin, biliverdin reductase, optogenetic tool.", "classifications": [], "creators": [ { "creator_type": "author", "first_name": "Kenju", "last_name": "Kobachi", "name": null }, { "creator_type": "author", "first_name": "Sota", "last_name": "Kuno", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Kenta", "last_name": "Sumiyama", "name": null }, { "creator_type": "author", "first_name": "Michiyuki", "last_name": "Matsuda", "name": null }, { "creator_type": "author", "first_name": "Kenta", "last_name": "Terai", "name": null } ], "identifiers": { "doi": { "normalized": "10.1247/csf.20010" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "32581154" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Biliverdine", "descriptor_ui": "D001664", "major_topic": false }, { "descriptor": "Embryo, Mammalian", "descriptor_ui": "D004622", "major_topic": false }, { "descriptor": "Fibroblasts", "descriptor_ui": "D005347", "major_topic": false }, { "descriptor": "Green Fluorescent Proteins", "descriptor_ui": "D049452", "major_topic": false }, { "descriptor": "HeLa Cells", "descriptor_ui": "D006367", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Oxidoreductases Acting on CH-CH Group Donors", "descriptor_ui": "D044925", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020 Aug 21", "date_precision": "day", "issue": "2", "normalized_date": "2020-08-21", "pages": "131-141", "proceedings_title": null, "publisher": "", "title": "Cell structure and function", "volume": "45", "year": 2020 }, "ssbd": { "database": [ "ssbd-database-000179" ], "repository": [ "ssbd-repos-000179" ] }, "title": "Biliverdin Reductase-A Deficiency Brighten and Sensitize Biliverdin-binding Chromoproteins.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Insulin regulates glucose metabolism through thousands of regulatory mechanisms; however, which regulatory mechanisms are keys to control glucose metabolism remains unknown. Here, we performed kinetic trans-omic analysis by integrating isotope-tracing glucose flux and phosphoproteomic data from insulin-stimulated adipocytes and built a kinetic mathematical model to identify key allosteric regulatory and phosphorylation events for enzymes. We identified nine reactions regulated by allosteric effectors and one by enzyme phosphorylation and determined the regulatory mechanisms for three of these reactions. Insulin stimulated glycolysis by promoting Glut4 activity by enhancing phosphorylation of AS160 at S595, stimulated fatty acid synthesis by promoting Acly activity through allosteric activation by glucose 6-phosphate or fructose 6-phosphate, and stimulated glutamate synthesis by alleviating allosteric inhibition of Gls by glutamate. Most of glycolytic reactions were regulated by amounts of substrates and products. Thus, phosphorylation or allosteric modulator-based regulation of only a few key enzymes was sufficient to change insulin-induced metabolism.", "classifications": [ { "id": "Kuroda", "label": "Group Kuroda", "parent": "Kuroda", "type": "group" }, { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Satoshi", "last_name": "Ohno", "name": null }, { "creator_type": "author", "first_name": "Lake-Ee", "last_name": "Quek", "name": null }, { "creator_type": "author", "first_name": "James R.", "last_name": "Krycer", "name": null }, { "creator_type": "author", "first_name": "Katsuyuki", "last_name": "Yugi", "name": null }, { "creator_type": "author", "first_name": "Akiyoshi", "last_name": "Hirayama", "name": null }, { "creator_type": "author", "first_name": "Satsuki", "last_name": "Ikeda", "name": null }, { "creator_type": "author", "first_name": "Futaba", "last_name": "Shoji", "name": null }, { "creator_type": "author", "first_name": "Kumi", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "David E.", "last_name": "James", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Kuroda", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.isci.2020.101479" }, "pmcid": { "normalized": "PMC7479629" }, "pmid": { "normalized": "32891058" } }, "mesh": [], "publication": { "conference_name": null, "date": "2020 Aug 20", "date_precision": "day", "issue": "9", "normalized_date": "2020-08-20", "pages": "101479", "proceedings_title": null, "publisher": "", "title": "iScience", "volume": "23", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Kinetic Trans-omic Analysis Reveals Key Regulatory Mechanisms for Insulin-Regulated Glucose Metabolism in Adipocytes.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "A photochemically crushable and regenerative metal-organic framework ((DTE)MOF) was developed by complexation of photochromic ligand (Py)DTE(open) and 5-nitroisophthalate (nip(2-)) with Cd(2+) in DMF/MeOH. (DTE)MOF ([Cd(nip)((Py)DTE(open))(H(2)O)(DMF)(2)](n)) was obtained as colorless crystals. Its crystal structure revealed that (DTE)MOF adopts a tubular structure with interlocked coordination networks and can accommodate guest molecules in its one-dimensional pores. When (DTE)MOF suspended in DMF/MeOH was exposed to UV light, its crystalline network, though thermally stable up to 260 degrees C, was readily crushed to afford a homogeneous blue-colored solution, via ring-closing isomerization of the constituent (Py)DTE(open) ligand into (Py)DTE(closed). Upon successive exposure of this solution to visible light, colorless MOF crystals identical to those of (DTE)MOF were regenerated. Light-responsive (DTE)MOF enabled highly efficient on-demand guest release.", "classifications": [ { "id": "Hijikata", "label": "Group Hijikata", "parent": "Tsuchiya", "type": "group" }, { "id": "Tsuchiya", "label": "Team Tsuchiya", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Toshiya", "last_name": "Matsui", "name": null }, { "creator_type": "author", "first_name": "Zhiyi", "last_name": "Chen", "name": null }, { "creator_type": "author", "first_name": "Jenny", "last_name": "Pirillo", "name": null }, { "creator_type": "author", "first_name": "Yuh", "last_name": "Hijikata", "name": null }, { "creator_type": "author", "first_name": "Takuzo", "last_name": "Aida", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/jacs.0c06615" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "32787258" } }, "mesh": [], "publication": { "conference_name": null, "date": "2020 Aug 19", "date_precision": "day", "issue": "33", "normalized_date": "2020-08-19", "pages": "14069-14073", "proceedings_title": null, "publisher": "", "title": "Journal of the American Chemical Society", "volume": "142", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Photochemically Crushable and Regenerative Metal-Organic Framework.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Cardiac tissue remodeling caused by hemodynamic overload is a major clinical outcome of heart failure. Uridine-responsive purinergic P2Y6 receptor (P2Y6R) contributes to the progression of cardiovascular remodeling in rodents, but it is not known whether inhibition of P2Y6R prevents or promotes heart failure. We demonstrate that inhibition of P2Y6R promotes pressure overload-induced sudden death and heart failure in mice. In neonatal cardiomyocytes, knockdown of P2Y6R significantly attenuated hypertrophic growth and cell death caused by hypotonic stimulation, indicating the involvement of P2Y6R in mechanical stress-induced myocardial dysfunction. Unexpectedly, compared with wild-type mice, deletion of P2Y6R promoted pressure overload-induced sudden death, as well as cardiac remodeling and dysfunction. Mice with cardiomyocyte-specific overexpression of P2Y6R also exhibited cardiac dysfunction and severe fibrosis. In contrast, P2Y6R deletion had little impact on oxidative stress-mediated cardiac dysfunction induced by doxorubicin treatment. These findings provide overwhelming evidence that systemic inhibition of P2Y6R exacerbates pressure overload-induced heart failure in mice, although P2Y6R in cardiomyocytes contributes to the progression of cardiac fibrosis.", "classifications": [ { "id": "Nishida", "label": "Group Nishida", "parent": "Nishida", "type": "group" }, { "id": "Nishimura", "label": "Group Nishimura", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Kakeru", "last_name": "Shimoda", "name": null }, { "creator_type": "author", "first_name": "Akiyuki", "last_name": "Nishimura", "name": null }, { "creator_type": "author", "first_name": "Caroline", "last_name": "Sunggip", "name": null }, { "creator_type": "author", "first_name": "Tomoya", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Kazuhiro", "last_name": "Nishiyama", "name": null }, { "creator_type": "author", "first_name": "Yuri", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Tomohiro", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Hidetoshi", "last_name": "Tozaki-Saitoh", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Tsuda", "name": null }, { "creator_type": "author", "first_name": "Motohiro", "last_name": "Nishida", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41598-020-70956-5" }, "pmcid": { "normalized": "PMC7434875" }, "pmid": { "normalized": "32811872" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Doxorubicin", "descriptor_ui": "D004317", "major_topic": false }, { "descriptor": "Fibrosis", "descriptor_ui": "D005355", "major_topic": false }, { "descriptor": "Heart Failure", "descriptor_ui": "D006333", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Myocytes, Cardiac", "descriptor_ui": "D032383", "major_topic": false }, { "descriptor": "Oxidative Stress", "descriptor_ui": "D018384", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Rats, Sprague-Dawley", "descriptor_ui": "D017207", "major_topic": false }, { "descriptor": "Receptors, Purinergic P2", "descriptor_ui": "D018048", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Stress, Mechanical", "descriptor_ui": "D013314", "major_topic": false }, { "descriptor": "Ventricular Remodeling", "descriptor_ui": "D020257", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020 Aug 18", "date_precision": "day", "issue": "1", "normalized_date": "2020-08-18", "pages": "13926", "proceedings_title": null, "publisher": "", "title": "Scientific reports", "volume": "10", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Modulation of P2Y6R expression exacerbates pressure overload-induced cardiac remodeling in mice.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Silicon photonics have attracted significant interest because of their potential in integrated photonics components and all-dielectric meta-optics elements. One major challenge is to achieve active control via strong photon-photon interactions, i.e. optical nonlinearity, which is intrinsically weak in silicon. To boost the nonlinear response, practical applications rely on resonant structures such as microring resonators or photonic crystals. Nevertheless, their typical footprints are larger than 10 mum. Here, we show that 100 nm silicon nano-resonators exhibit a giant photothermal nonlinearity, yielding 90% reversible and repeatable modulation from linear scattering response at low excitation intensities. The equivalent nonlinear index is five-orders larger compared with bulk, based on Mie resonance enhanced absorption and high-efficiency heating in thermally isolated nanostructures. Furthermore, the nanoscale thermal relaxation time reaches nanosecond. This large and fast nonlinearity leads to potential applications for GHz all-optical control at the nanoscale and super-resolution imaging of silicon.", "classifications": [ { "id": "Fujita", "label": "Group Fujita", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yi-Shiou", "last_name": "Duh", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Nagasaki", "name": null }, { "creator_type": "author", "first_name": "Yu-Lung", "last_name": "Tang", "name": null }, { "creator_type": "author", "first_name": "Pang-Han", "last_name": "Wu", "name": null }, { "creator_type": "author", "first_name": "Hao-Yu", "last_name": "Cheng", "name": null }, { "creator_type": "author", "first_name": "Te-Hsin", "last_name": "Yen", "name": null }, { "creator_type": "author", "first_name": "Hou-Xian", "last_name": "Ding", "name": null }, { "creator_type": "author", "first_name": "Kentaro", "last_name": "Nishida", "name": null }, { "creator_type": "author", "first_name": "Ikuto", "last_name": "Hotta", "name": null }, { "creator_type": "author", "first_name": "Jhen-Hong", "last_name": "Yang", "name": null }, { "creator_type": "author", "first_name": "Yu-Ping", "last_name": "Lo", "name": null }, { "creator_type": "author", "first_name": "Kuo-Ping", "last_name": "Chen", "name": null }, { "creator_type": "author", "first_name": "Katsumasa", "last_name": "Fujita", "name": null }, { "creator_type": "author", "first_name": "Chih-Wei", "last_name": "Chang", "name": null }, { "creator_type": "author", "first_name": "Kung-Hsuan", "last_name": "Lin", "name": null }, { "creator_type": "author", "first_name": "Junichi", "last_name": "Takahara", "name": null }, { "creator_type": "author", "first_name": "Shi-Wei", "last_name": "Chu", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41467-020-17846-6" }, "pmcid": { "normalized": "PMC7427991" }, "pmid": { "normalized": "32796839" } }, "mesh": [], "publication": { "conference_name": null, "date": "2020 Aug 14", "date_precision": "day", "issue": "1", "normalized_date": "2020-08-14", "pages": "4101", "proceedings_title": null, "publisher": "", "title": "Nature communications", "volume": "11", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Giant photothermal nonlinearity in a single silicon nanostructure.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Cu, Zn superoxide dismutase (SOD1) is a representative antioxidant enzyme that catalyzes dismutation of reactive oxygen species in cells. However, (E,E)-SOD1 mutants in which both copper and zinc ions were deleted exhibit pro-oxidant activity, contrary to their antioxidant nature, at physiological temperatures, following denaturation and subsequent recombination of Cu(2+). This oxidative property is likely related to the pathogenesis of amyotrophic lateral sclerosis (ALS); however, the mechanism by which Cu(2+) re-binds to the denatured (E,E)-SOD1 has not been elucidated, since the concentration of free copper ions in cells is almost zero. In this study, we prepared the (Cu,E) form in which only a zinc ion was deleted using ALS-linked mutant H43R (His43-->Arg) and found that (Cu,E)-H43R showed an increase in the pro-oxidant activity even at physiological temperature. The increase in the pro-oxidant activity of (Cu,E)-H43R was also observed in solution mimicking intracellular environment and at high temperature. These results suggest that the zinc-deficient (Cu,E) form can contribute to oxidative stress in cells, and that the formation of (E,E)-SOD1 together with the subsequent Cu(2+) rebinding is not necessary for the acquisition of the pro-oxidant activity.", "classifications": [ { "id": "Nakabayashi", "label": "Group Nakabayashi", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Chise", "last_name": "Nagao", "name": null }, { "creator_type": "author", "first_name": "Kunisato", "last_name": "Kuroi", "name": null }, { "creator_type": "author", "first_name": "Taiyu", "last_name": "Wakabayashi", "name": null }, { "creator_type": "author", "first_name": "Takakazu", "last_name": "Nakabayashi", "name": null } ], "identifiers": { "doi": { "normalized": "10.3390/molecules25163600" }, "pmcid": { "normalized": "PMC7464938" }, "pmid": { "normalized": "32784718" } }, "mesh": [ { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Kinetics", "descriptor_ui": "D007700", "major_topic": false }, { "descriptor": "Models, Molecular", "descriptor_ui": "D008958", "major_topic": false }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": true }, { "descriptor": "Protein Conformation, beta-Strand", "descriptor_ui": "D000072757", "major_topic": false }, { "descriptor": "Reactive Oxygen Species", "descriptor_ui": "D017382", "major_topic": false }, { "descriptor": "Superoxide Dismutase-1", "descriptor_ui": "D000072105", "major_topic": false }, { "descriptor": "Zinc", "descriptor_ui": "D015032", "major_topic": true } ], "publication": { "conference_name": null, "date": "2020 Aug 7", "date_precision": "day", "issue": "16", "normalized_date": "2020-08-07", "pages": "E3600", "proceedings_title": null, "publisher": "", "title": "Molecules (Basel, Switzerland)", "volume": "25", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Pro-Oxidant Activity of an ALS-Linked SOD1 Mutant in Zn-Deficient Form.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Psychological stress activates the hypothalamus, augments the sympathetic nervous output, and elevates blood pressure via excitation of the ventral medullary cardiovascular regions. However, anatomical and functional connectivity from the hypothalamus to the ventral medullary cardiovascular regions has not been fully elucidated. We investigated this issue by tract-tracing and functional imaging in rats. Retrograde tracing revealed the rostral ventrolateral medulla was innervated by neurons in the ipsilateral dorsomedial hypothalamus (DMH). Anterograde tracing showed DMH neurons projected to the ventral medullary cardiovascular regions with axon terminals in contiguity with tyrosine hydroxylase-immunoreactive neurons. By voltage-sensitive dye imaging, dynamics of ventral medullary activation evoked by electrical stimulation of the DMH were analyzed in the diencephalon-lower brainstem-spinal cord preparation of rats. Although the activation of the ventral medulla induced by single pulse stimulation of the DMH was brief, tetanic stimulation caused activation of the DMH sustained into the post-stimulus phase, resulting in delayed recovery. We suggest that prolonged excitation of the DMH, which is triggered by tetanic electrical stimulation and could also be triggered by psychological stress in a real life, induces further prolonged excitation of the medullary cardiovascular networks, and could contribute to the pathological elevation of blood pressure. The connectivity from the DMH to the medullary cardiovascular networks serves as a chronological amplifier of stress-induced sympathetic excitation. This notion will be the anatomical and pathophysiological basis to understand the mechanisms of stress-induced sustained augmentation of sympathetic activity.", "classifications": [ { "id": "Yokota", "label": "Group Yokota", "parent": "Enomoto", "type": "group" }, { "id": "Enomoto", "label": "Team Enomoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yosuke", "last_name": "Kono", "name": null }, { "creator_type": "author", "first_name": "Shigefumi", "last_name": "Yokota", "name": null }, { "creator_type": "author", "first_name": "Isato", "last_name": "Fukushi", "name": null }, { "creator_type": "author", "first_name": "Yosuke", "last_name": "Arima", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Onimaru", "name": null }, { "creator_type": "author", "first_name": "Shuntaro", "last_name": "Okazaki", "name": null }, { "creator_type": "author", "first_name": "Kotaro", "last_name": "Takeda", "name": null }, { "creator_type": "author", "first_name": "Itaru", "last_name": "Yazawa", "name": null }, { "creator_type": "author", "first_name": "Masashi", "last_name": "Yoshizawa", "name": null }, { "creator_type": "author", "first_name": "Yohei", "last_name": "Hasebe", "name": null }, { "creator_type": "author", "first_name": "Keiichi", "last_name": "Koizumi", "name": null }, { "creator_type": "author", "first_name": "Mieczyslaw", "last_name": "Pokorski", "name": null }, { "creator_type": "author", "first_name": "Takako", "last_name": "Toda", "name": null }, { "creator_type": "author", "first_name": "Kanji", "last_name": "Sugita", "name": null }, { "creator_type": "author", "first_name": "Yasumasa", "last_name": "Okada", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41598-020-70234-4" }, "pmcid": { "normalized": "PMC7414200" }, "pmid": { "normalized": "32770006" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Autonomic Pathways", "descriptor_ui": "D017776", "major_topic": false }, { "descriptor": "Dorsomedial Hypothalamic Nucleus", "descriptor_ui": "D004302", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Medulla Oblongata", "descriptor_ui": "D008526", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Rats, Wistar", "descriptor_ui": "D017208", "major_topic": false }, { "descriptor": "Sympathetic Nervous System", "descriptor_ui": "D013564", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020 Aug 7", "date_precision": "day", "issue": "1", "normalized_date": "2020-08-07", "pages": "13325", "proceedings_title": null, "publisher": "", "title": "Scientific reports", "volume": "10", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Structural and functional connectivity from the dorsomedial hypothalamus to the ventral medulla as a chronological amplifier of sympathetic outflow.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Plant grafting is conducted for fruit and vegetable propagation, whereby a piece of living tissue is attached to another through cell-cell adhesion. However, graft compatibility limits combinations to closely related species, and the mechanism is poorly understood. We found that Nicotiana is capable of graft adhesion with a diverse range of angiosperms. Comparative transcriptomic analyses on graft combinations indicated that a subclade of beta-1,4-glucanases secreted into the extracellular region facilitates cell wall reconstruction near the graft interface. Grafting was promoted by overexpression of the beta-1,4-glucanase. Using Nicotiana stem as an interscion, we produced tomato fruits on rootstocks from other plant families. These findings demonstrate that the process of cell-cell adhesion is a potential target to enhance plant grafting techniques.", "classifications": [ { "id": "Sato", "label": "Group Sato", "parent": "Tsuchiya", "type": "group" }, { "id": "Tsuchiya", "label": "Team Tsuchiya", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Michitaka", "last_name": "Notaguchi", "name": null }, { "creator_type": "author", "first_name": "Ken-Ichi", "last_name": "Kurotani", "name": null }, { "creator_type": "author", "first_name": "Yoshikatsu", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Ryo", "last_name": "Tabata", "name": null }, { "creator_type": "author", "first_name": "Yaichi", "last_name": "Kawakatsu", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Okayasu", "name": null }, { "creator_type": "author", "first_name": "Yu", "last_name": "Sawai", "name": null }, { "creator_type": "author", "first_name": "Ryo", "last_name": "Okada", "name": null }, { "creator_type": "author", "first_name": "Masashi", "last_name": "Asahina", "name": null }, { "creator_type": "author", "first_name": "Yasunori", "last_name": "Ichihashi", "name": null }, { "creator_type": "author", "first_name": "Ken", "last_name": "Shirasu", "name": null }, { "creator_type": "author", "first_name": "Takamasa", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Masaki", "last_name": "Niwa", "name": null }, { "creator_type": "author", "first_name": "Tetsuya", "last_name": "Higashiyama", "name": null } ], "identifiers": { "doi": { "normalized": "10.1126/science.abc3710" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "32764072" } }, "mesh": [ { "descriptor": "Cell Adhesion", "descriptor_ui": "D002448", "major_topic": false }, { "descriptor": "Cell Communication", "descriptor_ui": "D002450", "major_topic": false }, { "descriptor": "Cellulase", "descriptor_ui": "D002480", "major_topic": false }, { "descriptor": "Gene Expression Profiling", "descriptor_ui": "D020869", "major_topic": false }, { "descriptor": "Gene Expression Regulation, Plant", "descriptor_ui": "D018506", "major_topic": false }, { "descriptor": "Horticulture", "descriptor_ui": "D000080802", "major_topic": false }, { "descriptor": "Nicotiana", "descriptor_ui": "D014026", "major_topic": false }, { "descriptor": "Plant Proteins", "descriptor_ui": "D010940", "major_topic": false }, { "descriptor": "Transcription, Genetic", "descriptor_ui": "D014158", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020 Aug 7", "date_precision": "day", "issue": "6504", "normalized_date": "2020-08-07", "pages": "698-702", "proceedings_title": null, "publisher": "", "title": "Science (New York, N.Y.)", "volume": "369", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Cell-cell adhesion in plant grafting is facilitated by beta-1,4-glucanases.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Recent studies have demonstrated the usefulness of convolutional neural networks (CNNs) to classify images of melanoma, with accuracies comparable to those achieved by dermatologists. However, the performance of a CNN trained with only clinical images of a pigmented skin lesion in a clinical image classification task, in competition with dermatologists, has not been reported to date. In this study, we extracted 5846 clinical images of pigmented skin lesions from 3551 patients. Pigmented skin lesions included malignant tumors (malignant melanoma and basal cell carcinoma) and benign tumors (nevus, seborrhoeic keratosis, senile lentigo, and hematoma/hemangioma). We created the test dataset by randomly selecting 666 patients out of them and picking one image per patient, and created the training dataset by giving bounding-box annotations to the rest of the images (4732 images, 2885 patients). Subsequently, we trained a faster, region-based CNN (FRCNN) with the training dataset and checked the performance of the model on the test dataset. In addition, ten board-certified dermatologists (BCDs) and ten dermatologic trainees (TRNs) took the same tests, and we compared their diagnostic accuracy with FRCNN. For six-class classification, the accuracy of FRCNN was 86.2%, and that of the BCDs and TRNs was 79.5% (p = 0.0081) and 75.1% (p < 0.00001), respectively. For two-class classification (benign or malignant), the accuracy, sensitivity, and specificity were 91.5%, 83.3%, and 94.5% by FRCNN; 86.6%, 86.3%, and 86.6% by BCD; and 85.3%, 83.5%, and 85.9% by TRN, respectively. False positive rates and positive predictive values were 5.5% and 84.7% by FRCNN, 13.4% and 70.5% by BCD, and 14.1% and 68.5% by TRN, respectively. We compared the classification performance of FRCNN with 20 dermatologists. As a result, the classification accuracy of FRCNN was better than that of the dermatologists. In the future, we plan to implement this system in society and have it used by the general public, in order to improve the prognosis of skin cancer.", "classifications": [ { "id": "Hamamoto", "label": "Group Hamamoto", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Shunichi", "last_name": "Jinnai", "name": null }, { "creator_type": "author", "first_name": "Naoya", "last_name": "Yamazaki", "name": null }, { "creator_type": "author", "first_name": "Yuichiro", "last_name": "Hirano", "name": null }, { "creator_type": "author", "first_name": "Yohei", "last_name": "Sugawara", "name": null }, { "creator_type": "author", "first_name": "Yuichiro", "last_name": "Ohe", "name": null }, { "creator_type": "author", "first_name": "Ryuji", "last_name": "Hamamoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.3390/biom10081123" }, "pmcid": { "normalized": "PMC7465007" }, "pmid": { "normalized": "32751349" } }, "mesh": [ { "descriptor": "Deep Learning", "descriptor_ui": "D000077321", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Melanoma", "descriptor_ui": "D008545", "major_topic": false }, { "descriptor": "Neural Networks, Computer", "descriptor_ui": "D016571", "major_topic": false }, { "descriptor": "Skin", "descriptor_ui": "D012867", "major_topic": false }, { "descriptor": "Skin Neoplasms", "descriptor_ui": "D012878", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020 Jul 29", "date_precision": "day", "issue": "8", "normalized_date": "2020-07-29", "pages": "", "proceedings_title": null, "publisher": "", "title": "Biomolecules", "volume": "10", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "The Development of a Skin Cancer Classification System for Pigmented Skin Lesions Using Deep Learning.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Although the important roles of glycolysis in T cells have been demonstrated, the regulatory mechanism of glycolysis in activated T cells has not been fully elucidated. Furthermore, the influences of glycolytic failure on the T cell-dependent immune response in vivo remain unclear. We therefore assessed the role of glycolysis in the T cell-dependent immune response using T cell-specific Pgam1-deficient mice. Both CD8 and CD4 T cell-dependent immune responses were attenuated by Pgam1 deficiency. The helper T cell-dependent inflammation was ameliorated in Pgam1-deficient mice. Glycolysis augments the activation of mTOR complex 1 (mTORC1) and the T-cell receptor (TCR) signals. Glutamine acts as a metabolic hub in activated T cells, since the TCR-dependent increase in intracellular glutamine is required to augment glycolysis, increase mTORC1 activity and augment TCR signals. These findings suggest that mTORC1, glycolysis and glutamine affect each other and cooperate to induce T cell proliferation and differentiation.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Koji", "last_name": "Toriyama", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Kuwahara", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Kondoh", "name": null }, { "creator_type": "author", "first_name": "Takumi", "last_name": "Mikawa", "name": null }, { "creator_type": "author", "first_name": "Nobuaki", "last_name": "Takemori", "name": null }, { "creator_type": "author", "first_name": "Amane", "last_name": "Konishi", "name": null }, { "creator_type": "author", "first_name": "Toshihiro", "last_name": "Yorozuya", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Yamada", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Shiraishi", "name": null }, { "creator_type": "author", "first_name": "Masakatsu", "last_name": "Yamashita", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s42003-020-01122-w" }, "pmcid": { "normalized": "PMC7382475" }, "pmid": { "normalized": "32709928" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Cell Proliferation", "descriptor_ui": "D049109", "major_topic": false }, { "descriptor": "Glycolysis", "descriptor_ui": "D006019", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Immunity", "descriptor_ui": "D007109", "major_topic": false }, { "descriptor": "Lymphocyte Activation", "descriptor_ui": "D008213", "major_topic": false }, { "descriptor": "Mechanistic Target of Rapamycin Complex 1", "descriptor_ui": "D000076222", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Phosphoglycerate Mutase", "descriptor_ui": "D010736", "major_topic": false }, { "descriptor": "T-Lymphocytes", "descriptor_ui": "D013601", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020 Jul 24", "date_precision": "day", "issue": "1", "normalized_date": "2020-07-24", "pages": "394", "proceedings_title": null, "publisher": "", "title": "Communications biology", "volume": "3", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "T cell-specific deletion of Pgam1 reveals a critical role for glycolysis in T cell responses.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Dipeptides have attracted much attention as post-amino acids with physical properties and functions different from those of amino acids. However, a given dipeptide cannot be distinguished by mass spectrometry from its structural isomer with an opposite amino acid binding order unless these isomers are separated before introduction, which complicates the comprehensive analysis of dipeptides. Herein, a novel analytical platform for dipeptide analysis by capillary electrophoresis tandem mass spectrometry and liquid chromatography tandem mass spectrometry is developed. This method is used to quantitate 335 dipeptides and achieves excellent separation of structural isomers with opposite binding orders, high correlation coefficients, and low instrumental detection limits (0.088-83.1 nM). Moreover, acceptable recoveries (70-135%) are observed for most tested dipeptides in chicken liver samples spiked both before and after preparation. The developed method is also applied to the quantitation of dipeptides in the livers of mice fed different diets to detect 236 dipeptides, and the shift from a normal diet to a high-fat diet is shown to increase/decrease (p < 0.05, fold-change < 0.5) the contents of 0/29 dipeptides, respectively. The developed method is expected to facilitate the search for new dipeptide applications such as novel functional components of foods and biomarkers of diseases.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Ozawa", "name": null }, { "creator_type": "author", "first_name": "Akiyoshi", "last_name": "Hirayama", "name": null }, { "creator_type": "author", "first_name": "Takamasa", "last_name": "Ishikawa", "name": null }, { "creator_type": "author", "first_name": "Ryuhei", "last_name": "Kudo", "name": null }, { "creator_type": "author", "first_name": "Midori", "last_name": "Maruyama", "name": null }, { "creator_type": "author", "first_name": "Futaba", "last_name": "Shoji", "name": null }, { "creator_type": "author", "first_name": "Tomohito", "last_name": "Doke", "name": null }, { "creator_type": "author", "first_name": "Takuji", "last_name": "Ishimoto", "name": null }, { "creator_type": "author", "first_name": "Shoichi", "last_name": "Maruyama", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Masaru", "last_name": "Tomita", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/acs.analchem.0c01258" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "32538620" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Chromatography, Liquid", "descriptor_ui": "D002853", "major_topic": false }, { "descriptor": "Diet, High-Fat", "descriptor_ui": "D059305", "major_topic": false }, { "descriptor": "Dipeptides", "descriptor_ui": "D004151", "major_topic": false }, { "descriptor": "Electrophoresis, Capillary", "descriptor_ui": "D019075", "major_topic": false }, { "descriptor": "Limit of Detection", "descriptor_ui": "D057230", "major_topic": false }, { "descriptor": "Liver", "descriptor_ui": "D008099", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Reproducibility of Results", "descriptor_ui": "D015203", "major_topic": false }, { "descriptor": "Tandem Mass Spectrometry", "descriptor_ui": "D053719", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020 Jul 21", "date_precision": "day", "issue": "14", "normalized_date": "2020-07-21", "pages": "9799-9806", "proceedings_title": null, "publisher": "", "title": "Analytical chemistry", "volume": "92", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Comprehensive Dipeptide Profiling and Quantitation by Capillary Electrophoresis and Liquid Chromatography Coupled with Tandem Mass Spectrometry.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Necrotic cells elicit an inflammatory response through their endogenous factors with damage-associated molecular patterns. Blocking apoptosis in Drosophila wings leads to the necrosis-driven systemic immune response by unknown mechanisms. Here, we demonstrate that immune activation in response to necrotic cells is mediated by commensal gut microbiota. Removing the microbiome attenuates hyperactivation of the innate immune signaling IMD pathway in necrosis-induced flies. Necrotic cells in wings trigger Gluconobacter expansion in the gut. An isolated Gluconobacter sp. strain is sufficient for pathological IMD activation in necrosis-induced flies, while it is not inflammatory for control animals. In addition, bacterial colonization shifts the host metabolome and shortens the lifespan of necrosis-induced flies. This study shows that local necrosis triggers a pathological systemic inflammatory response through interaction between the host and the dysbiotic gut microbiome.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Hina", "last_name": "Kosakamoto", "name": null }, { "creator_type": "author", "first_name": "Toshitaka", "last_name": "Yamauchi", "name": null }, { "creator_type": "author", "first_name": "Yoriko", "last_name": "Akuzawa-Tokita", "name": null }, { "creator_type": "author", "first_name": "Kei", "last_name": "Nishimura", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Takumi", "last_name": "Murakami", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Mori", "name": null }, { "creator_type": "author", "first_name": "Kyosuke", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Ryo", "last_name": "Miyazaki", "name": null }, { "creator_type": "author", "first_name": "Akiko", "last_name": "Koto", "name": null }, { "creator_type": "author", "first_name": "Masayuki", "last_name": "Miura", "name": null }, { "creator_type": "author", "first_name": "Fumiaki", "last_name": "Obata", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.celrep.2020.107938" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "32698005" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Colony Count, Microbial", "descriptor_ui": "D015169", "major_topic": false }, { "descriptor": "Drosophila melanogaster", "descriptor_ui": "D004331", "major_topic": false }, { "descriptor": "Dysbiosis", "descriptor_ui": "D064806", "major_topic": false }, { "descriptor": "Gastrointestinal Microbiome", "descriptor_ui": "D000069196", "major_topic": false }, { "descriptor": "Gluconobacter", "descriptor_ui": "D020576", "major_topic": false }, { "descriptor": "Necrosis", "descriptor_ui": "D009336", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Wings, Animal", "descriptor_ui": "D014921", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020 Jul 21", "date_precision": "day", "issue": "3", "normalized_date": "2020-07-21", "pages": "107938", "proceedings_title": null, "publisher": "", "title": "Cell reports", "volume": "32", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Local Necrotic Cells Trigger Systemic Immune Activation via Gut Microbiome Dysbiosis in Drosophila.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Methods relying on the use of solid solutions can be used to produce solid materials having finely controlled physical properties. In the current investigation, we utilized this protocol to prepare solid solutions derived from two different Werner complexes in order to assess the effects of component ratios on acetone vapor adsorption properties. For this purpose, microcrystalline solid solutions with the basic elemental composition alpha-[Cu(PF6)2(py)4]x[Cu(CF3SO3)2(py)4]1-x (x = 0.75 and 0.5) (alpha-PAC-2-PF6/CF3SO3(x = 0.75 and 0.5), py = pyridine) were prepared by hexane induced precipitation of acetone solutions of [Cu(PF6)2(py)4] (PAC-2-PF6) and [Cu(CF3SO3)2(py)4] (PAC-2-CF3SO3). The results of acetone sorption isotherm measurements show that gate opening and closing pressures of the solid solutions are dependent on the composition ratios of PAC-2-CF3SO3 and PAC-2-PF6. Specifically, an increase in CF3SO3- anion content induces weakening of the interactions with acetone as a consequence of expansion of lattice constants and also strengthening host-host interactions. These effects cause an increase in gate opening and closing pressures.", "classifications": [ { "id": "Hijikata", "label": "Group Hijikata", "parent": "Tsuchiya", "type": "group" }, { "id": "Tsuchiya", "label": "Team Tsuchiya", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Shin-Ichiro", "last_name": "Noro", "name": null }, { "creator_type": "author", "first_name": "Yu", "last_name": "Song", "name": null }, { "creator_type": "author", "first_name": "Yutaro", "last_name": "Tanimoto", "name": null }, { "creator_type": "author", "first_name": "Yuh", "last_name": "Hijikata", "name": null }, { "creator_type": "author", "first_name": "Kazuya", "last_name": "Kubo", "name": null }, { "creator_type": "author", "first_name": "Takayoshi", "last_name": "Nakamura", "name": null } ], "identifiers": { "doi": { "normalized": "10.1039/d0dt01355b" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "32597427" } }, "mesh": [], "publication": { "conference_name": null, "date": "2020 Jul 17", "date_precision": "day", "issue": "27", "normalized_date": "2020-07-17", "pages": "9438-9443", "proceedings_title": null, "publisher": "", "title": "Dalton transactions (Cambridge, England : 2003)", "volume": "49", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Controlling the gate-sorption properties of solid solutions of Werner complexes by varying component ratios.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Studies have shown that epigenetic abnormalities are involved in various diseases, including cancer. In particular, in order to realize precision medicine, the integrated analysis of genetics and epigenetics is considered to be important; detailed epigenetic analysis in the medical field has been becoming increasingly important. In the epigenetics analysis, DNA methylation and histone modification analyses have been actively studied for a long time, and many important findings were accumulated. On the other hand, recently, attention has also been focused on RNA modification in the field of epigenetics; now it is known that RNA modification is associated with various biological functions, such as regulation of gene expression. Among RNA modifications, functional analysis of N(6)-methyladenosine (m(6)A), the most abundant RNA modification found from humans to plants is actively progressing, and it has also been known that m(6)A abnormality is involved in cancer and other diseases. Importantly, recent studies have shown that m(6)A is related to viral infections. Considering the current world situation under threat of viral infections, it is important to deepen knowledge of RNA modification from the viewpoint of viral diseases. Hence, in this review, we have summarized the recent findings regarding the roles of RNA modifications in biological functions, cancer biology, and virus infection, particularly focusing on m(6)A in mRNA.", "classifications": [ { "id": "Hamamoto", "label": "Group Hamamoto", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Ken", "last_name": "Asada", "name": null }, { "creator_type": "author", "first_name": "Amina", "last_name": "Bolatkan", "name": null }, { "creator_type": "author", "first_name": "Ken", "last_name": "Takasawa", "name": null }, { "creator_type": "author", "first_name": "Masaaki", "last_name": "Komatsu", "name": null }, { "creator_type": "author", "first_name": "Syuzo", "last_name": "Kaneko", "name": null }, { "creator_type": "author", "first_name": "Ryuji", "last_name": "Hamamoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.3390/biom10071071" }, "pmcid": { "normalized": "PMC7408378" }, "pmid": { "normalized": "32709063" } }, "mesh": [ { "descriptor": "Adenosine", "descriptor_ui": "D000241", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Epigenesis, Genetic", "descriptor_ui": "D044127", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Neoplasms", "descriptor_ui": "D009369", "major_topic": false }, { "descriptor": "RNA", "descriptor_ui": "D012313", "major_topic": false }, { "descriptor": "RNA Folding", "descriptor_ui": "D059370", "major_topic": false }, { "descriptor": "RNA Processing, Post-Transcriptional", "descriptor_ui": "D012323", "major_topic": true }, { "descriptor": "RNA Stability", "descriptor_ui": "D020871", "major_topic": false }, { "descriptor": "RNA Transport", "descriptor_ui": "D034443", "major_topic": false }, { "descriptor": "Virus Diseases", "descriptor_ui": "D014777", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020 Jul 17", "date_precision": "day", "issue": "7", "normalized_date": "2020-07-17", "pages": "", "proceedings_title": null, "publisher": "", "title": "Biomolecules", "volume": "10", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Critical Roles of N(6)-Methyladenosine (m(6)A) in Cancer and Virus Infection.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "A practical computation of fast Fourier transformation (FFT) based generalized two-dimensional (2D) correlation spectroscopy is described. Using simple sinusoids, we tested and confirmed that the method served effectively and properly, invariant to the changes of the number of data points of the time profiles. This computation is applicable to any type of waveforms in a versatile manner.", "classifications": [ { "id": "Nakabayashi", "label": "Group Nakabayashi", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Mengmeng", "last_name": "He", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Miyata", "name": null }, { "creator_type": "author", "first_name": "Takakazu", "last_name": "Nakabayashi", "name": null }, { "creator_type": "author", "first_name": "Shin-Ichi", "last_name": "Morita", "name": null } ], "identifiers": { "doi": { "normalized": "10.2116/analsci.20n005" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "32115465" } }, "mesh": [], "publication": { "conference_name": null, "date": "2020 Jul 10", "date_precision": "day", "issue": "7", "normalized_date": "2020-07-10", "pages": "885-887", "proceedings_title": null, "publisher": "", "title": "Analytical sciences : the international journal of the Japan Society for Analytical Chemistry", "volume": "36", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Practical Computation of FFT-based Generalized Two-dimensional Correlation Spectroscopy.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Sensory information is selectively or non-selectively enhanced and inhibited in the brain, but it remains unclear whether and how this occurs at the most peripheral level. Using in vivo calcium imaging of mouse olfactory bulb and olfactory epithelium in wild-type and mutant animals, we show that odors produce not only excitatory but also inhibitory responses in olfactory sensory neurons (OSNs). Heterologous assays indicate that odorants can act as agonists to some but inverse agonists to other odorant receptors. We also demonstrate that responses to odor mixtures are extensively suppressed or enhanced in OSNs. When high concentrations of odors are mixed, widespread antagonism suppresses the overall response amplitudes and density. In contrast, a mixture of low concentrations of odors often produces synergistic effects and boosts the faint odor inputs. Thus, odor responses are extensively tuned by inhibition, antagonism, and synergy at the most peripheral level, contributing to robust sensory representations.", "classifications": [ { "id": "Imai", "label": "Group Imai", "parent": "Enomoto", "type": "group" }, { "id": "Enomoto", "label": "Team Enomoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Shigenori", "last_name": "Inagaki", "name": null }, { "creator_type": "author", "first_name": "Ryo", "last_name": "Iwata", "name": null }, { "creator_type": "author", "first_name": "Masakazu", "last_name": "Iwamoto", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Imai", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.celrep.2020.107814" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "32610120" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Axons", "descriptor_ui": "D001369", "major_topic": false }, { "descriptor": "Biological Assay", "descriptor_ui": "D001681", "major_topic": false }, { "descriptor": "Mice, Transgenic", "descriptor_ui": "D008822", "major_topic": false }, { "descriptor": "Odorants", "descriptor_ui": "D009812", "major_topic": false }, { "descriptor": "Olfactory Mucosa", "descriptor_ui": "D009831", "major_topic": false }, { "descriptor": "Olfactory Receptor Neurons", "descriptor_ui": "D018034", "major_topic": false }, { "descriptor": "Presynaptic Terminals", "descriptor_ui": "D017729", "major_topic": false }, { "descriptor": "Receptors, Odorant", "descriptor_ui": "D018035", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020 Jun 30", "date_precision": "day", "issue": "13", "normalized_date": "2020-06-30", "pages": "107814", "proceedings_title": null, "publisher": "", "title": "Cell reports", "volume": "31", "year": 2020 }, "ssbd": { "database": [], "repository": [ "ssbd-repos-000156" ] }, "title": "Widespread Inhibition, Antagonism, and Synergy in Mouse Olfactory Sensory Neurons In Vivo.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: Lymphocytes circulate between peripheral lymphoid tissues via blood and lymphatic systems, and chemokine-induced migration is important in trafficking lymphocytes to distant sites. The small GTPase Rap1 is important in mediating lymphocyte motility, and Rap1-GEFs are involved in chemokine-mediated Rap1 activation. Here, we describe the roles and mechanisms of Rap1-GEFs in lymphocyte trafficking. RESULTS: In this study, we show that RA-GEF-1 and 2 (also known as Rapgef2 and 6) are key guanine nucleotide exchange factors (GEF) for Rap1 in lymphocyte trafficking. Mice harboring T cell-specific knockouts of Rapgef2/6 demonstrate defective homing and egress of T cells. Sphingosine-1-phosphate (S1P) as well as chemokines activates Rap1 in a RA-GEF-1/2-dependent manner, and their deficiency in T cells impairs Mst1 phosphorylation, cell polarization, and chemotaxis toward S1P gradient. On the other hand, B cell-specific knockouts of Rapgef2/6 impair chemokine-dependent retention of B cells in the bone marrow and passively facilitate egress. Phospholipase D2-dependent production of phosphatidic acid by these chemotactic factors determines spatial distribution of Rap1-GTP subsequent to membrane localization of RA-GEFs and induces the development of front membrane. On the other hand, basal de-phosphorylation of RA-GEFs is necessary for chemotactic factor-dependent increase in GEF activity for Rap1. CONCLUSIONS: We demonstrate here that subcellular distribution and activation of RA-GEFs are key factors for a directional movement of lymphocytes and that phosphatidic acid is critical for membrane translocation of RA-GEFs with chemokine stimulation.", "classifications": [ { "id": "Sawai", "label": "Group Sawai", "parent": "Sawai", "type": "group" }, { "id": "Sawai", "label": "Team Sawai", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Sayaka", "last_name": "Ishihara", "name": null }, { "creator_type": "author", "first_name": "Tsuyoshi", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Guangwei", "last_name": "Du", "name": null }, { "creator_type": "author", "first_name": "Daniele", "last_name": "Guardavaccaro", "name": null }, { "creator_type": "author", "first_name": "Akihiko", "last_name": "Nakajima", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Sawai", "name": null }, { "creator_type": "author", "first_name": "Tohru", "last_name": "Kataoka", "name": null }, { "creator_type": "author", "first_name": "Koko", "last_name": "Katagiri", "name": null } ], "identifiers": { "doi": { "normalized": "10.1186/s12915-020-00809-0" }, "pmcid": { "normalized": "PMC7325102" }, "pmid": { "normalized": "32600317" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "Cell Movement", "descriptor_ui": "D002465", "major_topic": true }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Guanine Nucleotide Exchange Factors", "descriptor_ui": "D020662", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Lymphocytes", "descriptor_ui": "D008214", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Phosphatidic Acids", "descriptor_ui": "D010712", "major_topic": false }, { "descriptor": "Phosphorylation", "descriptor_ui": "D010766", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020 Jun 29", "date_precision": "day", "issue": "1", "normalized_date": "2020-06-29", "pages": "75", "proceedings_title": null, "publisher": "", "title": "BMC biology", "volume": "18", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Phosphatidic acid-dependent localization and basal de-phosphorylation of RA-GEFs regulate lymphocyte trafficking.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "De novo establishment of DNA methylation is accomplished by DNMT3A and DNMT3B. Here, we analyze de novo DNA methylation in mouse embryonic fibroblasts (2i-MEFs) derived from DNA-hypomethylated 2i/L ES cells with genetic ablation of Dnmt3a or Dnmt3b. We identify 355 and 333 uniquely unmethylated genes in Dnmt3a and Dnmt3b knockout (KO) 2i-MEFs, respectively. We find that Dnmt3a is exclusively required for de novo methylation at both TSS regions and gene bodies of Polycomb group (PcG) target developmental genes, while Dnmt3b has a dominant role on the X chromosome. Consistent with this, tissue-specific DNA methylation at PcG target genes is substantially reduced in Dnmt3a KO embryos. Finally, we find that human patients with DNMT3 mutations exhibit reduced DNA methylation at regions that are hypomethylated in Dnmt3 KO 2i-MEFs. In conclusion, here we report a set of unique de novo DNA methylation target sites for both DNMT3 enzymes during mammalian development that overlap with hypomethylated sites in human patients.", "classifications": [ { "id": "Yamamoto", "label": "Group Yamamoto", "parent": "Toyoshima", "type": "group" }, { "id": "Toyoshima", "label": "Team Toyoshima", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Masaki", "last_name": "Yagi", "name": null }, { "creator_type": "author", "first_name": "Mio", "last_name": "Kabata", "name": null }, { "creator_type": "author", "first_name": "Akito", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Tomoyo", "last_name": "Ukai", "name": null }, { "creator_type": "author", "first_name": "Sho", "last_name": "Ohta", "name": null }, { "creator_type": "author", "first_name": "Kazuhiko", "last_name": "Nakabayashi", "name": null }, { "creator_type": "author", "first_name": "Masahito", "last_name": "Shimizu", "name": null }, { "creator_type": "author", "first_name": "Kenichiro", "last_name": "Hata", "name": null }, { "creator_type": "author", "first_name": "Alexander", "last_name": "Meissner", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Yasuhiro", "last_name": "Yamada", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41467-020-16989-w" }, "pmcid": { "normalized": "PMC7314859" }, "pmid": { "normalized": "32581223" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "DNA (Cytosine-5-)-Methyltransferases", "descriptor_ui": "D004248", "major_topic": false }, { "descriptor": "DNA Methylation", "descriptor_ui": "D019175", "major_topic": true }, { "descriptor": "DNA Methyltransferase 3A", "descriptor_ui": "D000090205", "major_topic": false }, { "descriptor": "DNA Methyltransferase 3B", "descriptor_ui": "D000097584", "major_topic": false }, { "descriptor": "Epigenetic Repression", "descriptor_ui": "D063185", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mouse Embryonic Stem Cells", "descriptor_ui": "D000066450", "major_topic": false }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": false }, { "descriptor": "Organ Specificity", "descriptor_ui": "D009928", "major_topic": false }, { "descriptor": "Polycomb-Group Proteins", "descriptor_ui": "D063146", "major_topic": false }, { "descriptor": "Transcription Initiation Site", "descriptor_ui": "D024363", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020 Jun 24", "date_precision": "day", "issue": "1", "normalized_date": "2020-06-24", "pages": "3199", "proceedings_title": null, "publisher": "", "title": "Nature communications", "volume": "11", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Identification of distinct loci for de novo DNA methylation by DNMT3A and DNMT3B during mammalian development.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "During collective migration of epithelial cells, the migration direction is aligned over a tissue-scale expanse. Although the collective cell migration is known to be directed by mechanical forces transmitted via cell-cell junctions, it remains elusive how the intercellular force transmission is coordinated with intracellular biochemical signaling to achieve collective movements. Here, we show that intercellular coupling of extracellular signal-regulated kinase (ERK)-mediated mechanochemical feedback yields long-distance transmission of guidance cues. Mechanical stretch activates ERK through epidermal growth factor receptor (EGFR) activation, and ERK activation triggers cell contraction. The contraction of the activated cell pulls neighboring cells, evoking another round of ERK activation and contraction in the neighbors. Furthermore, anisotropic contraction based on front-rear polarization guarantees unidirectional propagation of ERK activation, and in turn, the ERK activation waves direct multicellular alignment of the polarity, leading to long-range ordered migration. Our findings reveal that mechanical forces mediate intercellular signaling underlying sustained transmission of guidance cues for collective cell migration.", "classifications": [], "creators": [ { "creator_type": "author", "first_name": "Naoya", "last_name": "Hino", "name": null }, { "creator_type": "author", "first_name": "Leone", "last_name": "Rossetti", "name": null }, { "creator_type": "author", "first_name": "Ariadna", "last_name": "Marin-Llaurado", "name": null }, { "creator_type": "author", "first_name": "Kazuhiro", "last_name": "Aoki", "name": null }, { "creator_type": "author", "first_name": "Xavier", "last_name": "Trepat", "name": null }, { "creator_type": "author", "first_name": "Michiyuki", "last_name": "Matsuda", "name": null }, { "creator_type": "author", "first_name": "Tsuyoshi", "last_name": "Hirashima", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.devcel.2020.05.011" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "32497487" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Movement", "descriptor_ui": "D002465", "major_topic": true }, { "descriptor": "Cell Polarity", "descriptor_ui": "D016764", "major_topic": true }, { "descriptor": "Dogs", "descriptor_ui": "D004285", "major_topic": false }, { "descriptor": "ErbB Receptors", "descriptor_ui": "D066246", "major_topic": false }, { "descriptor": "Madin Darby Canine Kidney Cells", "descriptor_ui": "D061985", "major_topic": false }, { "descriptor": "MAP Kinase Signaling System", "descriptor_ui": "D020935", "major_topic": true }, { "descriptor": "Mechanotransduction, Cellular", "descriptor_ui": "D040542", "major_topic": true } ], "publication": { "conference_name": null, "date": "2020 Jun 22", "date_precision": "day", "issue": "6", "normalized_date": "2020-06-22", "pages": "646-660.e8", "proceedings_title": null, "publisher": "", "title": "Developmental cell", "volume": "53", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "ERK-Mediated Mechanochemical Waves Direct Collective Cell Polarization.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Mammalian pluripotent stem cells are thought to exist in two states: naive and primed. Generally, unlike those in rodents, pluripotent stem cells in primates, including humans, are regarded as being in the primed pluripotent state. Recently, several groups reported the existence of naive pluripotent stem cells in humans. In this study, we report the conversion of primed state embryonic stem cells from common marmoset, a New World monkey, to the naive state using transgenes. The cells showed typical naive state features, including dome-like colony morphology, growth factor requirement, gene expression profile, X chromosome activation state, and energy metabolic status. Moreover, interspecies chimeric embryo formation ability with mouse embryos was increased in the naive state. This technique can be applied in basic medical research using nonhuman primates, such as preclinical use of naive pluripotent stem cells and generating genetically modified primates.", "classifications": [ { "id": "Nikaido", "label": "Group Nikaido", "parent": "Fujiwara", "type": "group" }, { "id": "Fujiwara", "label": "Team Fujiwara", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Seiji", "last_name": "Shiozawa", "name": null }, { "creator_type": "author", "first_name": "Mayutaka", "last_name": "Nakajima", "name": null }, { "creator_type": "author", "first_name": "Junko", "last_name": "Okahara", "name": null }, { "creator_type": "author", "first_name": "Yoko", "last_name": "Kuortaki", "name": null }, { "creator_type": "author", "first_name": "Fumihiko", "last_name": "Kisa", "name": null }, { "creator_type": "author", "first_name": "Sho", "last_name": "Yoshimatsu", "name": null }, { "creator_type": "author", "first_name": "Mari", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Ikuko", "last_name": "Koya", "name": null }, { "creator_type": "author", "first_name": "Mika", "last_name": "Yoshimura", "name": null }, { "creator_type": "author", "first_name": "Yohei", "last_name": "Sasagawa", "name": null }, { "creator_type": "author", "first_name": "Itoshi", "last_name": "Nikaido", "name": null }, { "creator_type": "author", "first_name": "Erika", "last_name": "Sasaki", "name": null }, { "creator_type": "author", "first_name": "Hideyuki", "last_name": "Okano", "name": null } ], "identifiers": { "doi": { "normalized": "10.1089/scd.2019.0259" }, "pmcid": { "normalized": null }, "pmid": { "normalized": null } }, "mesh": [], "publication": { "conference_name": null, "date": "2020-06-15", "date_precision": "day", "issue": "12", "normalized_date": "2020-06-15", "pages": "761-773", "proceedings_title": null, "publisher": "Mary Ann Liebert, Inc., publishers", "title": "Stem Cells and Development", "volume": "29", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Primed to Naive-Like Conversion of the Common Marmoset Embryonic Stem Cells", "url": "https://www.liebertpub.com/doi/10.1089/scd.2019.0259", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The preparation of a novel Au(6) cluster bearing a bidentate mixed carbene-thiolate ligand is presented. The length of linker between the central benzimidazole and thiolate has a strong effect on the formation of cluster products, with a C(2) chain giving an Au(6) cluster, while a C(3) chain results in no evidence of cluster formation. Density functional theory analysis predicts a non-metallic cluster with a large HOMO-LUMO (3.2-3.6 eV) and optical gap.", "classifications": [ { "id": "Nanbo", "label": "Group Nanbo", "parent": "Tsuchiya", "type": "group" }, { "id": "Tsuchiya", "label": "Team Tsuchiya", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Kirsi", "last_name": "Salorinne", "name": null }, { "creator_type": "author", "first_name": "Renee W. Y.", "last_name": "Man", "name": null }, { "creator_type": "author", "first_name": "Paul A.", "last_name": "Lummis", "name": null }, { "creator_type": "author", "first_name": "Maryam Sabooni Asre", "last_name": "Hazer", "name": null }, { "creator_type": "author", "first_name": "Sami", "last_name": "Malola", "name": null }, { "creator_type": "author", "first_name": "Jacky C.-H.", "last_name": "Yim", "name": null }, { "creator_type": "author", "first_name": "Alex J.", "last_name": "Veinot", "name": null }, { "creator_type": "author", "first_name": "Wenxia", "last_name": "Zhou", "name": null }, { "creator_type": "author", "first_name": "Hannu", "last_name": "Hakkinen", "name": null }, { "creator_type": "author", "first_name": "Masakazu", "last_name": "Nambo", "name": null }, { "creator_type": "author", "first_name": "Cathleen M.", "last_name": "Crudden", "name": null } ], "identifiers": { "doi": { "normalized": "10.1039/d0cc01482f" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "32355943" } }, "mesh": [], "publication": { "conference_name": null, "date": "2020 Jun 7", "date_precision": "day", "issue": "45", "normalized_date": "2020-06-07", "pages": "6102-6105", "proceedings_title": null, "publisher": "", "title": "Chemical communications (Cambridge, England)", "volume": "56", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Synthesis and properties of an Au(6) cluster supported by a mixed N-heterocyclic carbene-thiolate ligand.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "NF-kappaB is a transcription factor that activates super enhancers (SEs) and typical enhancers (TEs) and triggers threshold and graded gene expression, respectively. However, the mechanisms by which NF-kappaB selectively participates in these enhancers remain unclear. Here we show using mouse primary B lymphocytes that SE activity simultaneously associates with chromatin opening and enriched NF-kappaB binding, resulting in a higher fold change and threshold expression upon B cell receptor (BCR) activation. The higher fold change results from longer DNA, whereas the threshold response is explained by synergy in DNA-NF-kappaB binding and is supported by the coexistence of PU.1 and NF-kappaB in a SE before cell stimulation. This model indicates that the pre-existing NF-kappaB functions as a seed and triggers its processive binding upon BCR activation. Our mathematical modeling of the single-cell transcriptome reveals an additional role for SEs in divergent clonal responses in B cells.", "classifications": [ { "id": "Nikaido", "label": "Group Nikaido", "parent": "Fujiwara", "type": "group" }, { "id": "Fujiwara", "label": "Team Fujiwara", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Hiroki", "last_name": "Michida", "name": null }, { "creator_type": "author", "first_name": "Hiroaki", "last_name": "Imoto", "name": null }, { "creator_type": "author", "first_name": "Hisaaki", "last_name": "Shinohara", "name": null }, { "creator_type": "author", "first_name": "Noriko", "last_name": "Yumoto", "name": null }, { "creator_type": "author", "first_name": "Masahide", "last_name": "Seki", "name": null }, { "creator_type": "author", "first_name": "Mana", "last_name": "Umeda", "name": null }, { "creator_type": "author", "first_name": "Tetsutaro", "last_name": "Hayashi", "name": null }, { "creator_type": "author", "first_name": "Itoshi", "last_name": "Nikaido", "name": null }, { "creator_type": "author", "first_name": "Takeya", "last_name": "Kasukawa", "name": null }, { "creator_type": "author", "first_name": "Yutaka", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Mariko", "last_name": "Okada-Hatakeyama", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.celrep.2020.107724" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "32492432" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "B-Lymphocytes", "descriptor_ui": "D001402", "major_topic": false }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Chromatin", "descriptor_ui": "D002843", "major_topic": false }, { "descriptor": "Enhancer Elements, Genetic", "descriptor_ui": "D004742", "major_topic": false }, { "descriptor": "Gene Expression Regulation", "descriptor_ui": "D005786", "major_topic": false }, { "descriptor": "Histones", "descriptor_ui": "D006657", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Models, Biological", "descriptor_ui": "D008954", "major_topic": false }, { "descriptor": "NF-kappa B", "descriptor_ui": "D016328", "major_topic": false }, { "descriptor": "Protein Binding", "descriptor_ui": "D011485", "major_topic": false }, { "descriptor": "Proto-Oncogene Protein Spi-1", "descriptor_ui": "D000099232", "major_topic": false }, { "descriptor": "Proto-Oncogene Proteins", "descriptor_ui": "D011518", "major_topic": false }, { "descriptor": "Trans-Activators", "descriptor_ui": "D015534", "major_topic": false }, { "descriptor": "Transcription Factor RelA", "descriptor_ui": "D051996", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020 Jun 2", "date_precision": "day", "issue": "9", "normalized_date": "2020-06-02", "pages": "107724", "proceedings_title": null, "publisher": "", "title": "Cell reports", "volume": "31", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "The Number of Transcription Factors at an Enhancer Determines Switch-like Gene Expression.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "", "classifications": [ { "id": "Nishikii", "label": "Group Nishikii", "parent": "Shintaku", "type": "group" }, { "id": "Shintaku", "label": "Team Shintaku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Risa", "last_name": "Konishi", "name": null }, { "creator_type": "author", "first_name": "Yosuke", "last_name": "Ishitsuka", "name": null }, { "creator_type": "author", "first_name": "Sae", "last_name": "Inoue", "name": null }, { "creator_type": "author", "first_name": "Akimasa", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Yoshiyuki", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Rei", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Naoko", "last_name": "Okiyama", "name": null }, { "creator_type": "author", "first_name": "Shigeru", "last_name": "Chiba", "name": null }, { "creator_type": "author", "first_name": "Hidekazu", "last_name": "Nishikii", "name": null }, { "creator_type": "author", "first_name": "Manabu", "last_name": "Fujimoto", "name": null }, { "creator_type": "author", "first_name": "Yasuhiro", "last_name": "Fujisawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1684/ejd.2020.3779" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "32666932" } }, "mesh": [ { "descriptor": "Carcinoma, Squamous Cell", "descriptor_ui": "D002294", "major_topic": false }, { "descriptor": "Conjunctival Neoplasms", "descriptor_ui": "D003230", "major_topic": false }, { "descriptor": "Fatal Outcome", "descriptor_ui": "D017809", "major_topic": false }, { "descriptor": "Graft vs Host Disease", "descriptor_ui": "D006086", "major_topic": false }, { "descriptor": "Head and Neck Neoplasms", "descriptor_ui": "D006258", "major_topic": false }, { "descriptor": "Hematopoietic Stem Cell Transplantation", "descriptor_ui": "D018380", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Keratoconjunctivitis Sicca", "descriptor_ui": "D007638", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Neoplasms, Second Primary", "descriptor_ui": "D016609", "major_topic": false }, { "descriptor": "Radiation Injuries", "descriptor_ui": "D011832", "major_topic": false }, { "descriptor": "Skin Neoplasms", "descriptor_ui": "D012878", "major_topic": false }, { "descriptor": "Sunlight", "descriptor_ui": "D013472", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020 Jun 1", "date_precision": "day", "issue": "3", "normalized_date": "2020-06-01", "pages": "313-314", "proceedings_title": null, "publisher": "", "title": "European journal of dermatology : EJD", "volume": "30", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Aggressive conjunctival carcinoma arising on poorly controlled sun-damaged graft-versus-host disease.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Recently, ion chromatography coupled with mass spectrometry has been used for the determination of anionic metabolites. However, connection with a mass spectrometer in this method is not straightforward because backpressure produced by the addition of a make-up solution often affects the peak resolutions of the target metabolites. To overcome this problem, we developed a capillary ion chromatography-mass spectrometry method utilizing a double coaxial electrospray ionization sprayer. This method was not affected by backpressure and the number of theoretical plates was about three times that of a conventional sprayer. Under optimized conditions, 44 anionic metabolites, including organic acids, sugar phosphates, nucleotides, and cofactors, were successfully separated and selectively detected with a Q Exactive mass spectrometer. The calibration curves of the tested metabolites showed excellent linearity within the range of 1-100,000 nmol/L and the correlation coefficient was greater than 0.991. The detection limits for these metabolites were between 1 and 500 nmol/L (0.4 and 200 fmol). The developed method was applied to the quantitation of anionic metabolites in cultured cancer cell samples with tumor necrosis factor (TNF)-alpha stimulation. This allowed for the successful determination of 105 metabolites. The levels of tricarboxylic acid cycle intermediates changed significantly after TNF-alpha stimulation. These results demonstrate that the developed method is a promising new tool for comprehensive analysis of anionic metabolites.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Akiyoshi", "last_name": "Hirayama", "name": null }, { "creator_type": "author", "first_name": "Sho", "last_name": "Tabata", "name": null }, { "creator_type": "author", "first_name": "Ryuhei", "last_name": "Kudo", "name": null }, { "creator_type": "author", "first_name": "Masako", "last_name": "Hasebe", "name": null }, { "creator_type": "author", "first_name": "Kumi", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Masaru", "last_name": "Tomita", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.chroma.2020.460914" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "32008820" } }, "mesh": [ { "descriptor": "Acids", "descriptor_ui": "D000143", "major_topic": false }, { "descriptor": "Anions", "descriptor_ui": "D000838", "major_topic": false }, { "descriptor": "Calibration", "descriptor_ui": "D002138", "major_topic": false }, { "descriptor": "Chromatography", "descriptor_ui": "D002845", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Limit of Detection", "descriptor_ui": "D057230", "major_topic": false }, { "descriptor": "Neoplasms", "descriptor_ui": "D009369", "major_topic": false }, { "descriptor": "Nucleotides", "descriptor_ui": "D009711", "major_topic": false }, { "descriptor": "Spectrometry, Mass, Electrospray Ionization", "descriptor_ui": "D021241", "major_topic": false }, { "descriptor": "Tumor Necrosis Factor-alpha", "descriptor_ui": "D014409", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020 May 24", "date_precision": "day", "issue": "", "normalized_date": "2020-05-24", "pages": "460914", "proceedings_title": null, "publisher": "", "title": "Journal of chromatography. A", "volume": "1619", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "The use of a double coaxial electrospray ionization sprayer improves the peak resolutions of anionic metabolites in capillary ion chromatography-mass spectrometry.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Nitric oxide (NO)-mediated production of cyclic guanosine 3',5'-monophosphate (cGMP) is a crucial signaling pathway that controls a wide array of neuronal functions, including exocytotic neurotransmitter release. A novel nitrated derivative of cGMP, 8-nitro-cGMP, not only activates cGMP-dependent protein kinase (PKG), but also has membrane permeability and redox activity to produce superoxide and S-guanylated protein. To date, no studies have addressed the effects of 8-nitro-cGMP on exocytotic kinetics. Here, we aimed to assess the 8-nitro-cGMP-mediated modulation of the depolarization-evoked catecholamine release from bovine chromaffin cells. 8-Nitro-cGMP was produced in bovine chromaffin cells dependent on NO donor. Amperometric analysis revealed that 8-nitro-cGMP modulated the kinetic parameters of secretory spikes from chromaffin cells, particularly decreased the speed of individual spikes, resulting in a reduced amperometric spike height, slope beta, and absolute value of slope gamma. The modulatory effects were independent of the PKG signal and superoxide production. This is the first study to demonstrate that 8-nitro-cGMP modulates exocytosis and provide insights into a novel regulatory mechanism of exocytosis.", "classifications": [ { "id": "Akaike", "label": "Group Akaike", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Hiroyasu", "last_name": "Tsutsuki", "name": null }, { "creator_type": "author", "first_name": "Shingo", "last_name": "Kasamatsu", "name": null }, { "creator_type": "author", "first_name": "Kohei", "last_name": "Kunieda", "name": null }, { "creator_type": "author", "first_name": "Tomoaki", "last_name": "Ida", "name": null }, { "creator_type": "author", "first_name": "Tomohiro", "last_name": "Sawa", "name": null }, { "creator_type": "author", "first_name": "Nobuyuki", "last_name": "Sasakawa", "name": null }, { "creator_type": "author", "first_name": "Takaaki", "last_name": "Akaike", "name": null }, { "creator_type": "author", "first_name": "Hideshi", "last_name": "Ihara", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.bbrc.2020.03.045" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "32201073" } }, "mesh": [ { "descriptor": "Adrenal Glands", "descriptor_ui": "D000311", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Catecholamines", "descriptor_ui": "D002395", "major_topic": false }, { "descriptor": "Cattle", "descriptor_ui": "D002417", "major_topic": false }, { "descriptor": "Cerebellum", "descriptor_ui": "D002531", "major_topic": false }, { "descriptor": "Chromaffin Cells", "descriptor_ui": "D019439", "major_topic": false }, { "descriptor": "Cyclic GMP", "descriptor_ui": "D006152", "major_topic": false }, { "descriptor": "Cyclic GMP-Dependent Protein Kinases", "descriptor_ui": "D017869", "major_topic": false }, { "descriptor": "Exocytosis", "descriptor_ui": "D005089", "major_topic": false }, { "descriptor": "Free Radical Scavengers", "descriptor_ui": "D016166", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Protein Kinase Inhibitors", "descriptor_ui": "D047428", "major_topic": false }, { "descriptor": "Superoxides", "descriptor_ui": "D013481", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020 May 21", "date_precision": "day", "issue": "1", "normalized_date": "2020-05-21", "pages": "225-230", "proceedings_title": null, "publisher": "", "title": "Biochemical and biophysical research communications", "volume": "526", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "8-Nitro-cGMP modulates exocytosis in adrenal chromaffin cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "In cell extrusion, a cell embedded in an epithelial monolayer loses its apical or basal surface and is subsequently squeezed out of the monolayer by neighboring cells. Cell extrusions occur during apoptosis, epithelial-mesenchymal transition, or precancerous cell invasion. They play important roles in embryogenesis, homeostasis, carcinogenesis, and many other biological processes. Although many of the molecular factors involved in cell extrusion are known, little is known about the mechanical basis of cell extrusion. We used a three-dimensional (3D) vertex model to investigate the mechanical stability of cells arranged in a monolayer with 3D foam geometry. We found that when the cells composing the monolayer have homogeneous mechanical properties, cells are extruded from the monolayer when the symmetry of the 3D geometry is broken because of an increase in cell density or a decrease in the number of topological neighbors around single cells. Those results suggest that mechanical instability inherent in the 3D foam geometry of epithelial monolayers is sufficient to drive epithelial cell extrusion. In the situation in which cells in the monolayer actively generate contractile or adhesive forces under the control of intrinsic genetic programs, the forces act to break the symmetry of the monolayer, leading to cell extrusion that is directed to the apical or basal side of the monolayer by the balance of contractile and adhesive forces on the apical and basal sides. Although our analyses are based on a simple mechanical model, our results are in accordance with observations of epithelial monolayers in vivo and consistently explain cell extrusions under a wide range of physiological and pathophysiological conditions. Our results illustrate the importance of a mechanical understanding of cell extrusion and provide a basis by which to link molecular regulation to physical processes.", "classifications": [ { "id": "JPMJCR1921", "label": "JPMJCR1921", "researcher": "Itaru Imayoshi", "type": "grant" }, { "id": "Fujimoto", "label": "Group Fujimoto", "parent": "Ueda", "type": "group" }, { "id": "Imayoshi", "label": "Group Imayoshi", "parent": "Imayoshi", "type": "group" }, { "id": "Okuda", "label": "Group Okuda", "parent": "Imayoshi", "type": "group" }, { "id": "Imayoshi", "label": "Team Imayoshi", "type": "team" }, { "id": "Ueda", "label": "Team Ueda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Satoru", "last_name": "Okuda", "name": null }, { "creator_type": "author", "first_name": "Koichi", "last_name": "Fujimoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.bpj.2020.03.028" }, "pmcid": { "normalized": "PMC7231918" }, "pmid": { "normalized": "32333862" } }, "mesh": [ { "descriptor": "Apoptosis", "descriptor_ui": "D017209", "major_topic": false }, { "descriptor": "Epithelial Cells", "descriptor_ui": "D004847", "major_topic": true }, { "descriptor": "Models, Biological", "descriptor_ui": "D008954", "major_topic": true } ], "publication": { "conference_name": null, "date": "2020 May 19", "date_precision": "day", "issue": "10", "normalized_date": "2020-05-19", "pages": "2549-2560", "proceedings_title": null, "publisher": "", "title": "Biophysical journal", "volume": "118", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "A Mechanical Instability in Planar Epithelial Monolayers Leads to Cell Extrusion.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "An amendment to this paper has been published and can be accessed via a link at the top of the paper.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Ki-Hyeon", "last_name": "Seong", "name": null }, { "creator_type": "author", "first_name": "Nhung Hong", "last_name": "Ly", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Katou", "name": null }, { "creator_type": "author", "first_name": "Naoko", "last_name": "Yokota", "name": null }, { "creator_type": "author", "first_name": "Ryuichiro", "last_name": "Nakato", "name": null }, { "creator_type": "author", "first_name": "Shinnosuke", "last_name": "Murakami", "name": null }, { "creator_type": "author", "first_name": "Akiyoshi", "last_name": "Hirayama", "name": null }, { "creator_type": "author", "first_name": "Shinji", "last_name": "Fukuda", "name": null }, { "creator_type": "author", "first_name": "Siu", "last_name": "Kang", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Katsuhiko", "last_name": "Shirahige", "name": null }, { "creator_type": "author", "first_name": "Shunsuke", "last_name": "Ishii", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s42003-020-0992-3" }, "pmcid": { "normalized": "PMC7235001" }, "pmid": { "normalized": "32424230" } }, "mesh": [], "publication": { "conference_name": null, "date": "2020 May 18", "date_precision": "day", "issue": "1", "normalized_date": "2020-05-18", "pages": "251", "proceedings_title": null, "publisher": "", "title": "Communications biology", "volume": "3", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Publisher Correction: Paternal restraint stress affects offspring metabolism via ATF-2 dependent mechanisms in Drosophila melanogaster germ cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Male animals may show alternative behaviors toward infants: attack or parenting. These behaviors are triggered by pup stimuli under the influence of the internal state, including the hormonal environment and/or social experiences. Converging data suggest that the medial preoptic area (MPOA) contributes to the behavioral selection toward the pup. However, the neural mechanisms underlying how integrated stimuli affect the MPOA-dependent behavioral selection remain unclear. Here we focus on the amygdalohippocampal area (AHi) that projects to MPOA and expresses oxytocin receptor, a hormone receptor mediating social behavior toward pups. We describe the activation of MPOA-projection AHi neurons in male mice by social contact with pups. Input mapping using the TRIO method reveals that MPOA-projection AHi neurons receive prominent inputs from several regions, including the thalamus, hypothalamus, and olfactory cortex. Electrophysiological and histologic analysis demonstrates that oxytocin modulates inhibitory synaptic responses on MPOA-projection AHi neurons. In addition, AHi forms the excitatory monosynapse to MPOA, and pharmacological activation of MPOA-projection AHi neurons enhances only aggressive behavior, but not parental behavior. Interestingly, this promoted behavior was related to social experience in male mice. Collectively, our results identified a presynaptic partner of MPOA that can integrate sensory input and hormonal state, and trigger pup-directed aggression.SIGNIFICANCE STATEMENT The medial preoptic area (MPOA) plays critical roles in parental behavior, such as motor control, motivation, and social interaction. The MPOA projects to multiple brain regions, and these projections contribute to several neural controls in parental behavior. In contrast, how inputs to MPOA are regulated by social and environmental information is poorly understood. In this study, we focus on the amygdalohippocampal area (AHi) that connects to MPOA and expresses oxytocin receptor. We demonstrate the disruption of the expression of parental behavior triggered by the activation of MPOA-projection AHi neurons. This behavior may be regulated not only by oxytocin but also by neural input from several regions.", "classifications": [ { "id": "Miyamichi", "label": "Group Miyamichi", "parent": "Enomoto", "type": "group" }, { "id": "Enomoto", "label": "Team Enomoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Keiichiro", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Yumi", "last_name": "Hamasaki", "name": null }, { "creator_type": "author", "first_name": "Kiyoshiro", "last_name": "Fukui", "name": null }, { "creator_type": "author", "first_name": "Kazuki", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Kazunari", "last_name": "Miyamichi", "name": null }, { "creator_type": "author", "first_name": "Masabumi", "last_name": "Minami", "name": null }, { "creator_type": "author", "first_name": "Taiju", "last_name": "Amano", "name": null } ], "identifiers": { "doi": { "normalized": "10.1523/jneurosci.0438-19.2020" }, "pmcid": { "normalized": "PMC7219291" }, "pmid": { "normalized": "32284340" } }, "mesh": [ { "descriptor": "Aggression", "descriptor_ui": "D000374", "major_topic": false }, { "descriptor": "Amygdala", "descriptor_ui": "D000679", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Brain Mapping", "descriptor_ui": "D001931", "major_topic": false }, { "descriptor": "Electrophysiological Phenomena", "descriptor_ui": "D055724", "major_topic": false }, { "descriptor": "Hippocampus", "descriptor_ui": "D006624", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Neural Inhibition", "descriptor_ui": "D009433", "major_topic": false }, { "descriptor": "Neural Pathways", "descriptor_ui": "D009434", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Paternal Behavior", "descriptor_ui": "D010332", "major_topic": false }, { "descriptor": "Preoptic Area", "descriptor_ui": "D011301", "major_topic": false }, { "descriptor": "Receptors, Oxytocin", "descriptor_ui": "D018045", "major_topic": false }, { "descriptor": "Social Behavior", "descriptor_ui": "D012919", "major_topic": false }, { "descriptor": "Social Environment", "descriptor_ui": "D012931", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020 May 13", "date_precision": "day", "issue": "20", "normalized_date": "2020-05-13", "pages": "3981-3994", "proceedings_title": null, "publisher": "", "title": "The Journal of neuroscience : the official journal of the Society for Neuroscience", "volume": "40", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Amygdalohippocampal Area Neurons That Project to the Preoptic Area Mediate Infant-Directed Attack in Male Mice.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "We propose a label-free method for measuring intracellular temperature using a Raman image of a cell in the O-H stretching band. Raman spectra of cultured cells and the medium were first measured at various temperatures using a Raman microscope and the intensity ratio of the two regions of the O-H stretching band was calculated. The intensity ratio varies linearly with temperature in both the medium and cells, and the resulting calibration lines allow simultaneous visualization of both intracellular and extracellular temperatures in a label-free manner. We applied this method to the measurement of temperature changes after the introduction of FCCP (carbonyl cyanide-p-trifluoromethoxyphenylhydrazone) in living cells. We observed a temperature rise in the cytoplasm and succeeded in obtaining an image of the change in intracellular temperature after the FCCP treatment.", "classifications": [ { "id": "Nakabayashi", "label": "Group Nakabayashi", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Toshiki", "last_name": "Sugimura", "name": null }, { "creator_type": "author", "first_name": "Shinji", "last_name": "Kajimoto", "name": null }, { "creator_type": "author", "first_name": "Takakazu", "last_name": "Nakabayashi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/anie.201915846" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "32048796" } }, "mesh": [ { "descriptor": "Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone", "descriptor_ui": "D002259", "major_topic": false }, { "descriptor": "Extracellular Space", "descriptor_ui": "D005110", "major_topic": false }, { "descriptor": "HeLa Cells", "descriptor_ui": "D006367", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Hydrogen", "descriptor_ui": "D006859", "major_topic": false }, { "descriptor": "Intracellular Space", "descriptor_ui": "D042541", "major_topic": false }, { "descriptor": "Molecular Imaging", "descriptor_ui": "D057054", "major_topic": true }, { "descriptor": "Oxygen", "descriptor_ui": "D010100", "major_topic": false }, { "descriptor": "Spectrum Analysis, Raman", "descriptor_ui": "D013059", "major_topic": true }, { "descriptor": "Temperature", "descriptor_ui": "D013696", "major_topic": true }, { "descriptor": "Water", "descriptor_ui": "D014867", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020 May 11", "date_precision": "day", "issue": "20", "normalized_date": "2020-05-11", "pages": "7755-7760", "proceedings_title": null, "publisher": "", "title": "Angewandte Chemie (International ed. in English)", "volume": "59", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Label-Free Imaging of Intracellular Temperature by Using the O-H Stretching Raman Band of Water.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The vestibular system, which is essential for maintaining balance, contributes to the sympathetic response. Although this response is involved in hypergravity load-induced hypothermia in mice, the underlying mechanism remains unknown. This study showed that hypergravity (2g) decreased plasma catecholamines, which resulted in hypoactivity of the interscapular brown adipose tissue (iBAT). Hypothermia induced by 2g load was significantly suppressed by administration of beta-adrenergic receptor agonists, suggesting the involvement of decrease in iBAT activity through sympathoinhibition. Bilateral chemogenetic activation of vesicular glutamate transporter 2 (VGLUT2)-expressing neurons in the vestibular nuclear complex (VNC) induced hypothermia. The VGLUT2-expressing neurons contributed to 2g load-induced hypothermia, since their deletion suppressed hypothermia. Although activation of vesicular gamma-aminobutyric acid transporter-expressing neurons in the VNC induced slight hypothermia instead of hyperthermia, their deletion did not affect 2g load-induced hypothermia. Thus, we concluded that 2g load-induced hypothermia resulted from sympathoinhibition via the activation of VGLUT2-expressing neurons in the VNC.", "classifications": [ { "id": "Yokota", "label": "Group Yokota", "parent": "Enomoto", "type": "group" }, { "id": "Enomoto", "label": "Team Enomoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Chikara", "last_name": "Abe", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Yamaoka", "name": null }, { "creator_type": "author", "first_name": "Yui", "last_name": "Maejima", "name": null }, { "creator_type": "author", "first_name": "Tomoe", "last_name": "Mikami", "name": null }, { "creator_type": "author", "first_name": "Shigefumi", "last_name": "Yokota", "name": null }, { "creator_type": "author", "first_name": "Akihiro", "last_name": "Yamanaka", "name": null }, { "creator_type": "author", "first_name": "Hironobu", "last_name": "Morita", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s42003-020-0950-0" }, "pmcid": { "normalized": "PMC7210111" }, "pmid": { "normalized": "32385401" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Gravitation", "descriptor_ui": "D006112", "major_topic": true }, { "descriptor": "Hypothermia", "descriptor_ui": "D007035", "major_topic": false }, { "descriptor": "Hypothermia, Induced", "descriptor_ui": "D007036", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Stress, Physiological", "descriptor_ui": "D013312", "major_topic": false }, { "descriptor": "Vesicular Glutamate Transport Protein 2", "descriptor_ui": "D050599", "major_topic": false }, { "descriptor": "Vestibular Nuclei", "descriptor_ui": "D014726", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020 May 8", "date_precision": "day", "issue": "1", "normalized_date": "2020-05-08", "pages": "227", "proceedings_title": null, "publisher": "", "title": "Communications biology", "volume": "3", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "VGLUT2-expressing neurons in the vestibular nuclear complex mediate gravitational stress-induced hypothermia in mice.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "EIF2AK4, which encodes the amino acid deficiency-sensing protein GCN2, has been implicated as a susceptibility gene for type 2 diabetes in the Japanese population. However, the mechanism by which GCN2 affects glucose homeostasis is unclear. Here, we show that insulin secretion is reduced in individuals harboring the risk allele of EIF2AK4 and that maintenance of GCN2-deficient mice on a high-fat diet results in a loss of pancreatic beta cell mass. Our data suggest that GCN2 senses amino acid deficiency in beta cells and limits signaling by mechanistic target of rapamycin complex 1 to prevent beta cell failure during the consumption of a high-fat diet.", "classifications": [ { "id": "Inaba", "label": "Group Inaba", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Ayumi", "last_name": "Kanno", "name": null }, { "creator_type": "author", "first_name": "Shun-Ichiro", "last_name": "Asahara", "name": null }, { "creator_type": "author", "first_name": "Ayuko", "last_name": "Furubayashi", "name": null }, { "creator_type": "author", "first_name": "Katsuhisa", "last_name": "Masuda", "name": null }, { "creator_type": "author", "first_name": "Risa", "last_name": "Yoshitomi", "name": null }, { "creator_type": "author", "first_name": "Emi", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Tomoko", "last_name": "Takai", "name": null }, { "creator_type": "author", "first_name": "Maki", "last_name": "Kimura-Koyanagi", "name": null }, { "creator_type": "author", "first_name": "Tomokazu", "last_name": "Matsuda", "name": null }, { "creator_type": "author", "first_name": "Alberto", "last_name": "Bartolome", "name": null }, { "creator_type": "author", "first_name": "Yushi", "last_name": "Hirota", "name": null }, { "creator_type": "author", "first_name": "Norihide", "last_name": "Yokoi", "name": null }, { "creator_type": "author", "first_name": "Yuka", "last_name": "Inaba", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Inoue", "name": null }, { "creator_type": "author", "first_name": "Michihiro", "last_name": "Matsumoto", "name": null }, { "creator_type": "author", "first_name": "Kenichi", "last_name": "Inoue", "name": null }, { "creator_type": "author", "first_name": "Takaya", "last_name": "Abe", "name": null }, { "creator_type": "author", "first_name": "Fan-Yan", "last_name": "Wei", "name": null }, { "creator_type": "author", "first_name": "Kazuhito", "last_name": "Tomizawa", "name": null }, { "creator_type": "author", "first_name": "Wataru", "last_name": "Ogawa", "name": null }, { "creator_type": "author", "first_name": "Susumu", "last_name": "Seino", "name": null }, { "creator_type": "author", "first_name": "Masato", "last_name": "Kasuga", "name": null }, { "creator_type": "author", "first_name": "Yoshiaki", "last_name": "Kido", "name": null } ], "identifiers": { "doi": { "normalized": "10.1172/jci.insight.128820" }, "pmcid": { "normalized": "PMC7253016" }, "pmid": { "normalized": "32376799" } }, "mesh": [ { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Amino Acids", "descriptor_ui": "D000596", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Diabetes Mellitus, Type 2", "descriptor_ui": "D003924", "major_topic": true }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Genetic Predisposition to Disease", "descriptor_ui": "D020022", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Insulin Secretion", "descriptor_ui": "D000078790", "major_topic": false }, { "descriptor": "Insulin-Secreting Cells", "descriptor_ui": "D050417", "major_topic": true }, { "descriptor": "Liver", "descriptor_ui": "D008099", "major_topic": true }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred ICR", "descriptor_ui": "D008813", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Protein Serine-Threonine Kinases", "descriptor_ui": "D017346", "major_topic": true }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020 May 7", "date_precision": "day", "issue": "9", "normalized_date": "2020-05-07", "pages": "128820", "proceedings_title": null, "publisher": "", "title": "JCI insight", "volume": "5", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "GCN2 regulates pancreatic beta cell mass by sensing intracellular amino acid levels.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The one-dimensional information of genomic DNA is hierarchically packed inside the eukaryotic cell nucleus and organized in a three-dimensional (3D) space. Genome-wide chromosome conformation capture (Hi-C) methods have uncovered the 3D genome organization and revealed multiscale chromatin domains of compartments and topologically associating domains (TADs). Moreover, single-nucleosome live-cell imaging experiments have revealed the dynamic organization of chromatin domains caused by stochastic thermal fluctuations. However, the mechanism underlying the dynamic regulation of such hierarchical and structural chromatin units within the microscale thermal medium remains unclear. Microrheology is a way to measure dynamic viscoelastic properties coupling between thermal microenvironment and mechanical response. Here, we propose a new, to our knowledge, microrheology for Hi-C data to analyze the dynamic compliance property as a measure of rigidness and flexibility of genomic regions along with the time evolution. Our method allows the conversion of an Hi-C matrix into the spectrum of the dynamic rheological property along the genomic coordinate of a single chromosome. To demonstrate the power of the technique, we analyzed Hi-C data during the neural differentiation of mouse embryonic stem cells. We found that TAD boundaries behave as more rigid nodes than the intra-TAD regions. The spectrum clearly shows the dynamic viscoelasticity of chromatin domain formation at different timescales. Furthermore, we characterized the appearance of synchronous and liquid-like intercompartment interactions in differentiated cells. Together, our microrheology data derived from Hi-C data provide physical insights into the dynamics of the 3D genome organization.", "classifications": [ { "id": "Onami", "label": "Group Onami", "parent": "Fujiwara", "type": "group" }, { "id": "Fujiwara", "label": "Team Fujiwara", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Soya", "last_name": "Shinkai", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Sugawara", "name": null }, { "creator_type": "author", "first_name": "Hisashi", "last_name": "Miura", "name": null }, { "creator_type": "author", "first_name": "Ichiro", "last_name": "Hiratani", "name": null }, { "creator_type": "author", "first_name": "Shuichi", "last_name": "Onami", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.bpj.2020.02.020" }, "pmcid": { "normalized": "PMC7203008" }, "pmid": { "normalized": "32191860" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Nucleus", "descriptor_ui": "D002467", "major_topic": false }, { "descriptor": "Chromatin", "descriptor_ui": "D002843", "major_topic": true }, { "descriptor": "Chromosomes", "descriptor_ui": "D002875", "major_topic": true }, { "descriptor": "DNA", "descriptor_ui": "D004247", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mouse Embryonic Stem Cells", "descriptor_ui": "D000066450", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020 May 5", "date_precision": "day", "issue": "9", "normalized_date": "2020-05-05", "pages": "2220-2228", "proceedings_title": null, "publisher": "", "title": "Biophysical journal", "volume": "118", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Microrheology for Hi-C Data Reveals the Spectrum of the Dynamic 3D Genome Organization.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Paternal environmental factors can epigenetically influence gene expressions in offspring. We demonstrate that restraint stress, an experimental model for strong psychological stress, to fathers affects the epigenome, transcriptome, and metabolome of offspring in a MEKK1-dATF2 pathway-dependent manner in Drosophila melanogaster. Genes involved in amino acid metabolism are upregulated by paternal restraint stress, while genes involved in glycolysis and the tricarboxylic acid (TCA) cycle are downregulated. The effects of paternal restraint stress are also confirmed by metabolome analysis. dATF-2 is highly expressed in testicular germ cells, and restraint stress also induces p38 activation in the testes. Restraint stress induces Unpaired 3 (Upd3), a Drosophila homolog of Interleukin 6 (IL-6). Moreover, paternal overexpression of upd3 in somatic cells disrupts heterochromatin in offspring but not in offspring from dATF-2 mutant fathers. These results indicate that paternal restraint stress affects metabolism in offspring via inheritance of dATF-2-dependent epigenetic changes.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Ki-Hyeon", "last_name": "Seong", "name": null }, { "creator_type": "author", "first_name": "Nhung Hong", "last_name": "Ly", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Katou", "name": null }, { "creator_type": "author", "first_name": "Naoko", "last_name": "Yokota", "name": null }, { "creator_type": "author", "first_name": "Ryuichiro", "last_name": "Nakato", "name": null }, { "creator_type": "author", "first_name": "Shinnosuke", "last_name": "Murakami", "name": null }, { "creator_type": "author", "first_name": "Akiyoshi", "last_name": "Hirayama", "name": null }, { "creator_type": "author", "first_name": "Shinji", "last_name": "Fukuda", "name": null }, { "creator_type": "author", "first_name": "Siu", "last_name": "Kang", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Katsuhiko", "last_name": "Shirahige", "name": null }, { "creator_type": "author", "first_name": "Shunsuke", "last_name": "Ishii", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s42003-020-0935-z" }, "pmcid": { "normalized": "PMC7198565" }, "pmid": { "normalized": "32367035" } }, "mesh": [ { "descriptor": "Activating Transcription Factor 2", "descriptor_ui": "D051698", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Drosophila melanogaster", "descriptor_ui": "D004331", "major_topic": false }, { "descriptor": "Drosophila Proteins", "descriptor_ui": "D029721", "major_topic": false }, { "descriptor": "Epigenome", "descriptor_ui": "D000081122", "major_topic": true }, { "descriptor": "Fathers", "descriptor_ui": "D005220", "major_topic": false }, { "descriptor": "Germ Cells", "descriptor_ui": "D005854", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "MAP Kinase Kinase Kinase 1", "descriptor_ui": "D048728", "major_topic": false }, { "descriptor": "Metabolome", "descriptor_ui": "D055442", "major_topic": true }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Transcriptome", "descriptor_ui": "D059467", "major_topic": true } ], "publication": { "conference_name": null, "date": "2020 May 4", "date_precision": "day", "issue": "1", "normalized_date": "2020-05-04", "pages": "208", "proceedings_title": null, "publisher": "", "title": "Communications biology", "volume": "3", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Paternal restraint stress affects offspring metabolism via ATF-2 dependent mechanisms in Drosophila melanogaster germ cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Recurrent hotspot (p.Gly17Val) mutations in RHOA encoding a small GTPase, together with loss-of-function mutations in TET2 encoding an epigenetic regulator, are genetic hallmarks of angioimmunoblastic T-cell lymphoma (AITL). Mice expressing the p.Gly17Val RHOA mutant on a Tet2-null background succumbed to AITL-like T-cell lymphomas due to deregulated T-cell receptor (TCR) signaling. Using these mice to investigate therapeutics for AITL, we found that dasatinib, a multikinase inhibitor prolonged their survival through inhibition of hyperactivated TCR signaling. A phase I clinical trial study of dasatinib monotherapy in 5 patients with relapsed/refractory AITL was performed. Dasatinib was started at a dose of 100 mg/body once a day and continued until days 10-78 (median day 58). All the evaluable patients achieved partial responses. Our findings suggest that AITL is highly dependent on TCR signaling and that dasatinib could be a promising candidate drug for AITL treatment. SIGNIFICANCE: Deregulated T-cell receptor signaling is a critical molecular event in angioimmunoblastic T-cell lymphoma and can be targeted with dasatinib.", "classifications": [ { "id": "Nishikii", "label": "Group Nishikii", "parent": "Shintaku", "type": "group" }, { "id": "Shintaku", "label": "Team Shintaku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Tran B.", "last_name": "Nguyen", "name": null }, { "creator_type": "author", "first_name": "Mamiko", "last_name": "Sakata-Yanagimoto", "name": null }, { "creator_type": "author", "first_name": "Manabu", "last_name": "Fujisawa", "name": null }, { "creator_type": "author", "first_name": "Sharna Tanzima", "last_name": "Nuhat", "name": null }, { "creator_type": "author", "first_name": "Hiroaki", "last_name": "Miyoshi", "name": null }, { "creator_type": "author", "first_name": "Yasuhito", "last_name": "Nannya", "name": null }, { "creator_type": "author", "first_name": "Koichi", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Kota", "last_name": "Fukumoto", "name": null }, { "creator_type": "author", "first_name": "Olivier A.", "last_name": "Bernard", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Kiyoki", "name": null }, { "creator_type": "author", "first_name": "Kantaro", "last_name": "Ishitsuka", "name": null }, { "creator_type": "author", "first_name": "Haruka", "last_name": "Momose", "name": null }, { "creator_type": "author", "first_name": "Shinichiro", "last_name": "Sukegawa", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Shinagawa", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Suyama", "name": null }, { "creator_type": "author", "first_name": "Yuji", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Hidekazu", "last_name": "Nishikii", "name": null }, { "creator_type": "author", "first_name": "Naoshi", "last_name": "Obara", "name": null }, { "creator_type": "author", "first_name": "Manabu", "last_name": "Kusakabe", "name": null }, { "creator_type": "author", "first_name": "Shintaro", "last_name": "Yanagimoto", "name": null }, { "creator_type": "author", "first_name": "Seishi", "last_name": "Ogawa", "name": null }, { "creator_type": "author", "first_name": "Koichi", "last_name": "Ohshima", "name": null }, { "creator_type": "author", "first_name": "Shigeru", "last_name": "Chiba", "name": null } ], "identifiers": { "doi": { "normalized": "10.1158/0008-5472.can-19-2787" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "32107212" } }, "mesh": [ { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Antineoplastic Agents", "descriptor_ui": "D000970", "major_topic": false }, { "descriptor": "Dasatinib", "descriptor_ui": "D000069439", "major_topic": false }, { "descriptor": "Dioxygenases", "descriptor_ui": "D049308", "major_topic": false }, { "descriptor": "Disease Models, Animal", "descriptor_ui": "D004195", "major_topic": false }, { "descriptor": "DNA-Binding Proteins", "descriptor_ui": "D004268", "major_topic": false }, { "descriptor": "Drug Administration Schedule", "descriptor_ui": "D004334", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Immunoblastic Lymphadenopathy", "descriptor_ui": "D007119", "major_topic": false }, { "descriptor": "Interferon-gamma", "descriptor_ui": "D007371", "major_topic": false }, { "descriptor": "Interleukins", "descriptor_ui": "D007378", "major_topic": false }, { "descriptor": "Lymphoma, T-Cell", "descriptor_ui": "D016399", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred BALB C", "descriptor_ui": "D008807", "major_topic": false }, { "descriptor": "Mice, Nude", "descriptor_ui": "D008819", "major_topic": false }, { "descriptor": "Mice, Transgenic", "descriptor_ui": "D008822", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Proto-Oncogene Proteins", "descriptor_ui": "D011518", "major_topic": false }, { "descriptor": "Proto-Oncogene Proteins c-vav", "descriptor_ui": "D051567", "major_topic": false }, { "descriptor": "Receptors, Antigen, T-Cell", "descriptor_ui": "D011948", "major_topic": false }, { "descriptor": "rhoA GTP-Binding Protein", "descriptor_ui": "D020742", "major_topic": false }, { "descriptor": "Tumor Necrosis Factor-alpha", "descriptor_ui": "D014409", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020 May 1", "date_precision": "day", "issue": "9", "normalized_date": "2020-05-01", "pages": "1875-1884", "proceedings_title": null, "publisher": "", "title": "Cancer research", "volume": "80", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Dasatinib Is an Effective Treatment for Angioimmunoblastic T-cell Lymphoma.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "SUMMARY: Phenotypic variability in a population of cells can work as the bet-hedging of the cells under an unpredictably changing environment, the typical example of which is the bacterial persistence. To understand the strategy to control such phenomena, it is indispensable to identify the phenotype of each cell and its inheritance. Although recent advancements in microfluidic technology offer us useful lineage data, they are insufficient to directly identify the phenotypes of the cells. An alternative approach is to infer the phenotype from the lineage data by latent-variable estimation. To this end, however, we must resolve the bias problem in the inference from lineage called survivorship bias. In this work, we clarify how the survivorship bias distorts statistical estimations. We then propose a latent-variable estimation algorithm without the survivorship bias from lineage trees based on an expectation-maximization (EM) algorithm, which we call lineage EM algorithm (LEM). LEM provides a statistical method to identify the traits of the cells applicable to various kinds of lineage data. AVAILABILITY AND IMPLEMENTATION: An implementation of LEM is available at https://github.com/so-nakashima/Lineage-EM-algorithm. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.", "classifications": [ { "id": "Kobayashi", "label": "Group Kobayashi", "parent": "Wakamoto", "type": "group" }, { "id": "Wakamoto", "label": "Team Wakamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "So", "last_name": "Nakashima", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Sughiyama", "name": null }, { "creator_type": "author", "first_name": "Tetsuya J.", "last_name": "Kobayashi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1093/bioinformatics/btaa040" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "31971568" } }, "mesh": [ { "descriptor": "Algorithms", "descriptor_ui": "D000465", "major_topic": true }, { "descriptor": "Cell Lineage", "descriptor_ui": "D019070", "major_topic": false }, { "descriptor": "Phenotype", "descriptor_ui": "D010641", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020 May 1", "date_precision": "day", "issue": "9", "normalized_date": "2020-05-01", "pages": "2829-2838", "proceedings_title": null, "publisher": "", "title": "Bioinformatics (Oxford, England)", "volume": "36", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Lineage EM algorithm for inferring latent states from cellular lineage trees.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Whole-organ/body three-dimensional (3D) staining and imaging have been enduring challenges in histology. By dissecting the complex physicochemical environment of the staining system, we developed a highly optimized 3D staining imaging pipeline based on CUBIC. Based on our precise characterization of biological tissues as an electrolyte gel, we experimentally evaluated broad 3D staining conditions by using an artificial tissue-mimicking material. The combination of optimized conditions allows a bottom-up design of a superior 3D staining protocol that can uniformly label whole adult mouse brains, an adult marmoset brain hemisphere, an ~1 cm(3) tissue block of a postmortem adult human cerebellum, and an entire infant marmoset body with dozens of antibodies and cell-impermeant nuclear stains. The whole-organ 3D images collected by light-sheet microscopy are used for computational analyses and whole-organ comparison analysis between species. This pipeline, named CUBIC-HistoVIsion, thus offers advanced opportunities for organ- and organism-scale histological analysis of multicellular systems.", "classifications": [ { "id": "Miyamichi", "label": "Group Miyamichi", "parent": "Enomoto", "type": "group" }, { "id": "Enomoto", "label": "Team Enomoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Etsuo A.", "last_name": "Susaki", "name": null }, { "creator_type": "author", "first_name": "Chika", "last_name": "Shimizu", "name": null }, { "creator_type": "author", "first_name": "Akihiro", "last_name": "Kuno", "name": null }, { "creator_type": "author", "first_name": "Kazuki", "last_name": "Tainaka", "name": null }, { "creator_type": "author", "first_name": "Xiang", "last_name": "Li", "name": null }, { "creator_type": "author", "first_name": "Kengo", "last_name": "Nishi", "name": null }, { "creator_type": "author", "first_name": "Ken", "last_name": "Morishima", "name": null }, { "creator_type": "author", "first_name": "Hiroaki", "last_name": "Ono", "name": null }, { "creator_type": "author", "first_name": "Koji L.", "last_name": "Ode", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Saeki", "name": null }, { "creator_type": "author", "first_name": "Kazunari", "last_name": "Miyamichi", "name": null }, { "creator_type": "author", "first_name": "Kaoru", "last_name": "Isa", "name": null }, { "creator_type": "author", "first_name": "Chihiro", "last_name": "Yokoyama", "name": null }, { "creator_type": "author", "first_name": "Hiroki", "last_name": "Kitaura", "name": null }, { "creator_type": "author", "first_name": "Masako", "last_name": "Ikemura", "name": null }, { "creator_type": "author", "first_name": "Tetsuo", "last_name": "Ushiku", "name": null }, { "creator_type": "author", "first_name": "Yoshihiro", "last_name": "Shimizu", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Takaomi C.", "last_name": "Saido", "name": null }, { "creator_type": "author", "first_name": "Masashi", "last_name": "Fukayama", "name": null }, { "creator_type": "author", "first_name": "Hirotaka", "last_name": "Onoe", "name": null }, { "creator_type": "author", "first_name": "Kazushige", "last_name": "Touhara", "name": null }, { "creator_type": "author", "first_name": "Tadashi", "last_name": "Isa", "name": null }, { "creator_type": "author", "first_name": "Akiyoshi", "last_name": "Kakita", "name": null }, { "creator_type": "author", "first_name": "Mitsuhiro", "last_name": "Shibayama", "name": null }, { "creator_type": "author", "first_name": "Hiroki R.", "last_name": "Ueda", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41467-020-15906-5" }, "pmcid": { "normalized": "PMC7184626" }, "pmid": { "normalized": "32341345" } }, "mesh": [ { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Animals, Newborn", "descriptor_ui": "D000831", "major_topic": false }, { "descriptor": "Brain", "descriptor_ui": "D001921", "major_topic": false }, { "descriptor": "Callithrix", "descriptor_ui": "D002144", "major_topic": false }, { "descriptor": "Cerebellum", "descriptor_ui": "D002531", "major_topic": false }, { "descriptor": "Electrolytes", "descriptor_ui": "D004573", "major_topic": true }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Fluorescent Dyes", "descriptor_ui": "D005456", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Image Processing, Computer-Assisted", "descriptor_ui": "D007091", "major_topic": false }, { "descriptor": "Imaging, Three-Dimensional", "descriptor_ui": "D021621", "major_topic": true }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Microscopy, Fluorescence", "descriptor_ui": "D008856", "major_topic": true }, { "descriptor": "Optical Imaging", "descriptor_ui": "D061848", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020 Apr 27", "date_precision": "day", "issue": "1", "normalized_date": "2020-04-27", "pages": "1982", "proceedings_title": null, "publisher": "", "title": "Nature communications", "volume": "11", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Versatile whole-organ/body staining and imaging based on electrolyte-gel properties of biological tissues.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Tumor-binding peptides such as human epidermal growth factor receptor 2 (HER2)-binding peptides are attractive therapeutic and diagnostic options for cancer. However, the HER2-binding peptides (HBPs) developed thus far are susceptible to proteolysis and lose their affinity to HER2 in vivo. In this report, a method to create a HER2-binding fluctuation-regulated affinity protein (HBP-FLAP) consisting of a fibronectin type III domain (FN3) scaffold with a structurally immobilized HBP is presented. HBPs were selected by phage-library screening and grafted onto FN3 to create FN3-HBPs, and the HBP-FLAP with the highest affinity (HBP sequence: YCAHNM) was identified after affinity maturation of the grafted HBP. HBP-FLAP containing the YCAHNM peptide showed increased proteolysis-resistance, binding to HER2 with a dissociation constant (K D) of 58 nM in ELISA and 287 nM in biolayer interferometry and specifically detects HER2-expressing cancer cells. In addition, HBP-FLAP clearly delineated HER2-expressing tumors with a half-life of 6 h after intravenous injection into tumor-bearing mice. FN3-based FLAP is an excellent platform for developing target-binding small proteins for clinical applications.", "classifications": [ { "id": "Kuchimaru", "label": "Group Kuchimaru", "parent": "Shintaku", "type": "group" }, { "id": "Shintaku", "label": "Team Shintaku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Wanaporn", "last_name": "Yimchuen", "name": null }, { "creator_type": "author", "first_name": "Tetsuya", "last_name": "Kadonosono", "name": null }, { "creator_type": "author", "first_name": "Yumi", "last_name": "Ota", "name": null }, { "creator_type": "author", "first_name": "Shinichi", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Maika", "last_name": "Kitazawa", "name": null }, { "creator_type": "author", "first_name": "Tadashi", "last_name": "Shiozawa", "name": null }, { "creator_type": "author", "first_name": "Takahiro", "last_name": "Kuchimaru", "name": null }, { "creator_type": "author", "first_name": "Masumi", "last_name": "Taki", "name": null }, { "creator_type": "author", "first_name": "Yuji", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Shinae", "last_name": "Kizaka-Kondoh", "name": null } ], "identifiers": { "doi": { "normalized": "10.1039/d0ra00427h" }, "pmcid": { "normalized": "PMC9052545" }, "pmid": { "normalized": "35495466" } }, "mesh": [], "publication": { "conference_name": null, "date": "2020 Apr 16", "date_precision": "day", "issue": "26", "normalized_date": "2020-04-16", "pages": "15154-15162", "proceedings_title": null, "publisher": "", "title": "RSC advances", "volume": "10", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Strategic design to create HER2-targeting proteins with target-binding peptides immobilized on a fibronectin type III domain scaffold.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Lung cancer is one of the leading causes of death worldwide. Therefore, understanding the factors linked to patient survival is essential. Recently, multi-omics analysis has emerged, allowing for patient groups to be classified according to prognosis and at a more individual level, to support the use of precision medicine. Here, we combined RNA expression and miRNA expression with clinical information, to conduct a multi-omics analysis, using publicly available datasets (the cancer genome atlas (TCGA) focusing on lung adenocarcinoma (LUAD)). We were able to successfully subclass patients according to survival. The classifiers we developed, using inferred labels obtained from patient subtypes showed that a support vector machine (SVM), gave the best classification results, with an accuracy of 0.82 with the test dataset. Using these subtypes, we ranked genes based on RNA expression levels. The top 25 genes were investigated, to elucidate the mechanisms that underlie patient prognosis. Bioinformatics analyses showed that the expression levels of six out of 25 genes (ERO1B, DPY19L1, NCAM1, RET, MARCH1, and SLC7A8) were associated with LUAD patient survival (p < 0.05), and pathway analyses indicated that major cancer signaling was altered in the subtypes.", "classifications": [ { "id": "Hamamoto", "label": "Group Hamamoto", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Ken", "last_name": "Asada", "name": null }, { "creator_type": "author", "first_name": "Kazuma", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Samuel", "last_name": "Joutard", "name": null }, { "creator_type": "author", "first_name": "Masashi", "last_name": "Tubaki", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Ken", "last_name": "Takasawa", "name": null }, { "creator_type": "author", "first_name": "Masaaki", "last_name": "Komatsu", "name": null }, { "creator_type": "author", "first_name": "Syuzo", "last_name": "Kaneko", "name": null }, { "creator_type": "author", "first_name": "Jun", "last_name": "Sese", "name": null }, { "creator_type": "author", "first_name": "Ryuji", "last_name": "Hamamoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.3390/biom10040524" }, "pmcid": { "normalized": "PMC7225957" }, "pmid": { "normalized": "32235589" } }, "mesh": [ { "descriptor": "Adenocarcinoma of Lung", "descriptor_ui": "D000077192", "major_topic": false }, { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Genomics", "descriptor_ui": "D023281", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Kaplan-Meier Estimate", "descriptor_ui": "D053208", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Prognosis", "descriptor_ui": "D011379", "major_topic": false }, { "descriptor": "Support Vector Machine", "descriptor_ui": "D060388", "major_topic": false }, { "descriptor": "Unsupervised Machine Learning", "descriptor_ui": "D000069558", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020 Mar 30", "date_precision": "day", "issue": "4", "normalized_date": "2020-03-30", "pages": "", "proceedings_title": null, "publisher": "", "title": "Biomolecules", "volume": "10", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Uncovering Prognosis-Related Genes and Pathways by Multi-Omics Analysis in Lung Cancer.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Detailed spatial information of low-molecular weight compound distribution, especially in the brain, is crucial to understanding their mechanism of actions. Imaging techniques that can directly visualize drugs in the brain at a high resolution will complement existing tools for drug distribution analysis. Here, we performed surface-enhanced Raman scattering (SERS) imaging using a bioorthogonal alkyne tag to visualize drugs directly in situ at a high resolution. Focusing on the selective serotonin reuptake inhibitor S-citalopram (S-Cit), which possesses a nitrile group, we substituted an alkynyl group into its structure and synthesized alkynylated S-Cit (Alk-S-Cit). The brain transitivity and the serotonin reuptake inhibition of Alk-S-Cit were not significantly different as compared with S-Cit. Alk-S-Cit was visualized in the coronal mouse brain section using SERS imaging with silver nanoparticles. Furthermore, SERS imaging combined with fluorescence microscopy allowed Alk-S-Cit to be visualized in the adjacent neuronal membranes, as well as in the brain vessel and parenchyma. Therefore, our multimodal imaging technique is an effective method for detecting low-molecular weight compounds in their original tissue environment and can potentially offer additional information regarding the precise spatial distribution of such drugs.", "classifications": [ { "id": "Fujita", "label": "Group Fujita", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Masato", "last_name": "Tanuma", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Kasai", "name": null }, { "creator_type": "author", "first_name": "Kazuki", "last_name": "Bando", "name": null }, { "creator_type": "author", "first_name": "Naoyuki", "last_name": "Kotoku", "name": null }, { "creator_type": "author", "first_name": "Kazuo", "last_name": "Harada", "name": null }, { "creator_type": "author", "first_name": "Masafumi", "last_name": "Minoshima", "name": null }, { "creator_type": "author", "first_name": "Kosuke", "last_name": "Higashino", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Kimishima", "name": null }, { "creator_type": "author", "first_name": "Masayoshi", "last_name": "Arai", "name": null }, { "creator_type": "author", "first_name": "Yukio", "last_name": "Ago", "name": null }, { "creator_type": "author", "first_name": "Kaoru", "last_name": "Seiriki", "name": null }, { "creator_type": "author", "first_name": "Kazuya", "last_name": "Kikuchi", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Kawata", "name": null }, { "creator_type": "author", "first_name": "Katsumasa", "last_name": "Fujita", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Hashimoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1172/jci.insight.133348" }, "pmcid": { "normalized": "PMC7213792" }, "pmid": { "normalized": "32125287" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Antidepressive Agents, Second-Generation", "descriptor_ui": "D018687", "major_topic": false }, { "descriptor": "Brain", "descriptor_ui": "D001921", "major_topic": false }, { "descriptor": "Citalopram", "descriptor_ui": "D015283", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Microscopy, Fluorescence", "descriptor_ui": "D008856", "major_topic": false }, { "descriptor": "Multimodal Imaging", "descriptor_ui": "D064847", "major_topic": false }, { "descriptor": "Neuroimaging", "descriptor_ui": "D059906", "major_topic": false }, { "descriptor": "Selective Serotonin Reuptake Inhibitors", "descriptor_ui": "D017367", "major_topic": false }, { "descriptor": "Spectrum Analysis, Raman", "descriptor_ui": "D013059", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020 Mar 26", "date_precision": "day", "issue": "6", "normalized_date": "2020-03-26", "pages": "133348", "proceedings_title": null, "publisher": "", "title": "JCI insight", "volume": "5", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Direct visualization of an antidepressant analog using surface-enhanced Raman scattering in the brain.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The stratum corneum plays a crucial role in epidermal barrier function. Various changes occur in granular cells at the uppermost stratum granulosum during cornification. To understand the temporal details of this process, we visualized the cell shape and organelles of cornifying keratinocytes in a living human epidermal equivalent model. Three-dimensional time-lapse imaging with a two-photon microscope revealed that the granular cells did not simply flatten but first temporarily expanded in thickness just before flattening during cornification. Moreover, before expansion, intracellular vesicles abruptly stopped moving, and mitochondria were depolarized. When mitochondrial morphology and quantity were assessed, granular cells with fewer, mostly punctate mitochondria tended to transition to corneocytes. Several minutes after flattening, DNA leakage from the nucleus was visualized. We also observed extension of the cell-flattening time induced by the suppression of filaggrin expression. Overall, we successfully visualized the time-course of cornification, which describes temporal relationships between alterations in the transition from granular cells to corneocytes.", "classifications": [ { "id": "Nagayama", "label": "Group Nagayama", "parent": "Fujiwara", "type": "group" }, { "id": "Fujiwara", "label": "Team Fujiwara", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Sari", "last_name": "Ipponjima", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Umino", "name": null }, { "creator_type": "author", "first_name": "Masaharu", "last_name": "Nagayama", "name": null }, { "creator_type": "author", "first_name": "Mitsuhiro", "last_name": "Denda", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41598-020-62240-3" }, "pmcid": { "normalized": "PMC7099034" }, "pmid": { "normalized": "32218450" } }, "mesh": [ { "descriptor": "Cell Shape", "descriptor_ui": "D048430", "major_topic": false }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Filaggrin Proteins", "descriptor_ui": "D000091344", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Keratinocytes", "descriptor_ui": "D015603", "major_topic": false }, { "descriptor": "Microscopy", "descriptor_ui": "D008853", "major_topic": false }, { "descriptor": "Models, Biological", "descriptor_ui": "D008954", "major_topic": false }, { "descriptor": "Organelles", "descriptor_ui": "D015388", "major_topic": false }, { "descriptor": "S100 Proteins", "descriptor_ui": "D009418", "major_topic": false }, { "descriptor": "Time-Lapse Imaging", "descriptor_ui": "D059008", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020 Mar 26", "date_precision": "day", "issue": "1", "normalized_date": "2020-03-26", "pages": "5515", "proceedings_title": null, "publisher": "", "title": "Scientific reports", "volume": "10", "year": 2020 }, "ssbd": { "database": [ "ssbd-database-000188" ], "repository": [ "ssbd-repos-000188" ] }, "title": "Live imaging of alterations in cellular morphology and organelles during cornification using an epidermal equivalent model.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The occurrence of repetitive genomic changes that provide a selective growth advantage in pluripotent stem cells is of concern for their clinical application. However, the effect of different culture conditions on the underlying mutation rate is unknown. Here we show that the mutation rate in two human embryonic stem cell lines derived and banked for clinical application is low and not substantially affected by culture with Rho Kinase inhibitor, commonly used in their routine maintenance. However, the mutation rate is reduced by >50% in cells cultured under 5% oxygen, when we also found alterations in imprint methylation and reversible DNA hypomethylation. Mutations are evenly distributed across the chromosomes, except for a slight increase on the X-chromosome, and an elevation in intergenic regions suggesting that chromatin structure may affect mutation rate. Overall the results suggest that pluripotent stem cells are not subject to unusually high rates of genetic or epigenetic alterations.", "classifications": [ { "id": "Yusa", "label": "Group Yusa", "parent": "Eiraku", "type": "group" }, { "id": "Eiraku", "label": "Team Eiraku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Oliver", "last_name": "Thompson", "name": null }, { "creator_type": "author", "first_name": "Ferdinand", "last_name": "von Meyenn", "name": null }, { "creator_type": "author", "first_name": "Zoe", "last_name": "Hewitt", "name": null }, { "creator_type": "author", "first_name": "John", "last_name": "Alexander", "name": null }, { "creator_type": "author", "first_name": "Andrew", "last_name": "Wood", "name": null }, { "creator_type": "author", "first_name": "Richard", "last_name": "Weightman", "name": null }, { "creator_type": "author", "first_name": "Sian", "last_name": "Gregory", "name": null }, { "creator_type": "author", "first_name": "Felix", "last_name": "Krueger", "name": null }, { "creator_type": "author", "first_name": "Simon", "last_name": "Andrews", "name": null }, { "creator_type": "author", "first_name": "Ivana", "last_name": "Barbaric", "name": null }, { "creator_type": "author", "first_name": "Paul J.", "last_name": "Gokhale", "name": null }, { "creator_type": "author", "first_name": "Harry D.", "last_name": "Moore", "name": null }, { "creator_type": "author", "first_name": "Wolf", "last_name": "Reik", "name": null }, { "creator_type": "author", "first_name": "Marta", "last_name": "Milo", "name": null }, { "creator_type": "author", "first_name": "Serena", "last_name": "Nik-Zainal", "name": null }, { "creator_type": "author", "first_name": "Kosuke", "last_name": "Yusa", "name": null }, { "creator_type": "author", "first_name": "Peter W.", "last_name": "Andrews", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41467-020-15271-3" }, "pmcid": { "normalized": "PMC7089967" }, "pmid": { "normalized": "32251294" } }, "mesh": [ { "descriptor": "Cell Culture Techniques", "descriptor_ui": "D018929", "major_topic": false }, { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "Chromosomes, Human, X", "descriptor_ui": "D041321", "major_topic": false }, { "descriptor": "Culture Media", "descriptor_ui": "D003470", "major_topic": false }, { "descriptor": "DNA Methylation", "descriptor_ui": "D019175", "major_topic": false }, { "descriptor": "DNA Mutational Analysis", "descriptor_ui": "D004252", "major_topic": false }, { "descriptor": "DNA, Intergenic", "descriptor_ui": "D021901", "major_topic": false }, { "descriptor": "Epigenesis, Genetic", "descriptor_ui": "D044127", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mutation Rate", "descriptor_ui": "D059645", "major_topic": true }, { "descriptor": "Oxidative Stress", "descriptor_ui": "D018384", "major_topic": false }, { "descriptor": "Oxygen", "descriptor_ui": "D010100", "major_topic": false }, { "descriptor": "Pluripotent Stem Cells", "descriptor_ui": "D039904", "major_topic": false }, { "descriptor": "Sequence Analysis, RNA", "descriptor_ui": "D017423", "major_topic": false }, { "descriptor": "Whole Genome Sequencing", "descriptor_ui": "D000073336", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020 Mar 23", "date_precision": "day", "issue": "1", "normalized_date": "2020-03-23", "pages": "1528", "proceedings_title": null, "publisher": "", "title": "Nature communications", "volume": "11", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Low rates of mutation in clinical grade human pluripotent stem cells under different culture conditions.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Sialidase cleaves sialic acid residues from a sialoglycoconjugate: oligosaccharides, glycolipids and glycoproteins that contain sialic acid. Histochemical imaging of the mouse pancreas using a benzothiazolylphenol-based sialic acid derivative (BTP3-Neu5Ac), a highly sensitive histochemical imaging probe used to assess sialidase activity, showed that pancreatic islets have intense sialidase activity. The sialidase inhibitor 2,3-dehydro-2-deoxy-N-acetylneuraminic acid (DANA) remarkably enhances glutamate release from hippocampal neurons. Since there are many similar processes between synaptic vesicle exocytosis and secretory granule exocytosis, we investigated the effect of DANA on insulin release from β-cells. Insulin release was induced in INS-1D cells by treatment with 8.3 mM glucose, and the release was enhanced by treatment with DANA. In a mouse intraperitoneal glucose tolerance test, the increase in serum insulin levels was enhanced by intravenous injection with DANA. However, under fasting conditions, insulin release was not enhanced by treatment with DANA. Calcium oscillations induced by 8.3 mM glucose treatment of INS-1D cells were not affected by DANA. Blood insulin levels in sialidase isozyme Neu3-deficient mice were significantly higher than those in WT mice under ad libitum feeding conditions, but the levels were not different under fasting conditions. These results indicate that DANA is a glucose-dependent potentiator of insulin secretion. The sialidase inhibitor may be useful for anti-diabetic treatment with a low risk of hypoglycemia.", "classifications": [ { "id": "Suzuki", "label": "Group Suzuki", "parent": "Takekawa", "type": "group" }, { "id": "Takekawa", "label": "Team Takekawa", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Akira", "last_name": "Minami", "name": null }, { "creator_type": "author", "first_name": "Yuka", "last_name": "Fujita", "name": null }, { "creator_type": "author", "first_name": "Sumika", "last_name": "Shimba", "name": null }, { "creator_type": "author", "first_name": "Mako", "last_name": "Shiratori", "name": null }, { "creator_type": "author", "first_name": "Yukiko K.", "last_name": "Kaneko", "name": null }, { "creator_type": "author", "first_name": "Toshiaki", "last_name": "Sawatani", "name": null }, { "creator_type": "author", "first_name": "Tadamune", "last_name": "Otsubo", "name": null }, { "creator_type": "author", "first_name": "Kiyoshi", "last_name": "Ikeda", "name": null }, { "creator_type": "author", "first_name": "Hiroaki", "last_name": "Kanazawa", "name": null }, { "creator_type": "author", "first_name": "Yasuyo", "last_name": "Mikami", "name": null }, { "creator_type": "author", "first_name": "Risa", "last_name": "Sekita", "name": null }, { "creator_type": "author", "first_name": "Yuuki", "last_name": "Kurebayashi", "name": null }, { "creator_type": "author", "first_name": "Tadanobu", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Taeko", "last_name": "Miyagi", "name": null }, { "creator_type": "author", "first_name": "Tomohisa", "last_name": "Ishikawa", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Suzuki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41598-020-62203-8" }, "pmcid": { "normalized": "PMC7089948" }, "pmid": { "normalized": "32251344" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Benzothiazoles", "descriptor_ui": "D052160", "major_topic": false }, { "descriptor": "Calcium Signaling", "descriptor_ui": "D020013", "major_topic": false }, { "descriptor": "Coloring Agents", "descriptor_ui": "D004396", "major_topic": false }, { "descriptor": "Drug Evaluation, Preclinical", "descriptor_ui": "D004353", "major_topic": false }, { "descriptor": "Fasting", "descriptor_ui": "D005215", "major_topic": false }, { "descriptor": "Glucose", "descriptor_ui": "D005947", "major_topic": false }, { "descriptor": "Glucose Tolerance Test", "descriptor_ui": "D005951", "major_topic": false }, { "descriptor": "Hypoglycemic Agents", "descriptor_ui": "D007004", "major_topic": false }, { "descriptor": "Injections, Intravenous", "descriptor_ui": "D007275", "major_topic": false }, { "descriptor": "Insulin", "descriptor_ui": "D007328", "major_topic": false }, { "descriptor": "Insulin Secretion", "descriptor_ui": "D000078790", "major_topic": false }, { "descriptor": "Insulin-Secreting Cells", "descriptor_ui": "D050417", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "N-Acetylneuraminic Acid", "descriptor_ui": "D019158", "major_topic": false }, { "descriptor": "Neuraminidase", "descriptor_ui": "D009439", "major_topic": false }, { "descriptor": "Sialic Acids", "descriptor_ui": "D012794", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020 Mar 23", "date_precision": "day", "issue": "1", "normalized_date": "2020-03-23", "pages": "5198", "proceedings_title": null, "publisher": "", "title": "Scientific reports", "volume": "10", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "The sialidase inhibitor 2,3-dehydro-2-deoxy-N-acetylneuraminic acid is a glucose-dependent potentiator of insulin secretion.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Notch signaling controls proliferation of multipotent pancreatic progenitor cells (MPCs) and their segregation into bipotent progenitors (BPs) and unipotent pro-acinar cells (PACs). Here, we showed that fast ultradian oscillations of the ligand Dll1 and the transcriptional effector Hes1 were crucial for MPC expansion, and changes in Hes1 oscillation parameters were associated with selective adoption of BP or PAC fate. Conversely, Jag1, a uniformly expressed ligand, restrained MPC growth. However, when its expression later segregated to PACs, Jag1 became critical for the specification of all but the most proximal BPs, and BPs were entirely lost in Jag1; Dll1 double mutants. Anatomically, ductal morphogenesis and organ architecture are minimally perturbed in Jag1 mutants until later stages, when ductal remodeling fails, and signs of acinar-to-ductal metaplasia appear. Our study thus uncovers that oscillating Notch activity in the developing pancreas, modulated by Jag1, is required to coordinate MPC growth and fate.", "classifications": [ { "id": "Imayoshi", "label": "Group Imayoshi", "parent": "Imayoshi", "type": "group" }, { "id": "Imayoshi", "label": "Team Imayoshi", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Philip Allan", "last_name": "Seymour", "name": null }, { "creator_type": "author", "first_name": "Caitlin Alexis", "last_name": "Collin", "name": null }, { "creator_type": "author", "first_name": "Anuska la Rosa", "last_name": "Egeskov-Madsen", "name": null }, { "creator_type": "author", "first_name": "Mette Christine", "last_name": "Jorgensen", "name": null }, { "creator_type": "author", "first_name": "Hiromi", "last_name": "Shimojo", "name": null }, { "creator_type": "author", "first_name": "Itaru", "last_name": "Imayoshi", "name": null }, { "creator_type": "author", "first_name": "Kristian Honnens", "last_name": "de Lichtenberg", "name": null }, { "creator_type": "author", "first_name": "Raphael", "last_name": "Kopan", "name": null }, { "creator_type": "author", "first_name": "Ryoichiro", "last_name": "Kageyama", "name": null }, { "creator_type": "author", "first_name": "Palle", "last_name": "Serup", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.devcel.2020.01.015" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "32059775" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Calcium-Binding Proteins", "descriptor_ui": "D002135", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": true }, { "descriptor": "Cell Lineage", "descriptor_ui": "D019070", "major_topic": false }, { "descriptor": "Embryonic Stem Cells", "descriptor_ui": "D053595", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Gene Expression Regulation, Developmental", "descriptor_ui": "D018507", "major_topic": false }, { "descriptor": "Jagged-1 Protein", "descriptor_ui": "D000072100", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": false }, { "descriptor": "Pancreas", "descriptor_ui": "D010179", "major_topic": false }, { "descriptor": "Periodicity", "descriptor_ui": "D010507", "major_topic": false }, { "descriptor": "Receptors, Notch", "descriptor_ui": "D051880", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": true }, { "descriptor": "Transcription Factor HES-1", "descriptor_ui": "D000072056", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020 Mar 23", "date_precision": "day", "issue": "6", "normalized_date": "2020-03-23", "pages": "731-747.e8", "proceedings_title": null, "publisher": "", "title": "Developmental cell", "volume": "52", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Jag1 Modulates an Oscillatory Dll1-Notch-Hes1 Signaling Module to Coordinate Growth and Fate of Pancreatic Progenitors.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The denatured Cu, Zn superoxide dismutase (SOD1) has the pro-oxidant activity that is suggested to be related with the pathogenesis of amyotrophic lateral sclerosis (ALS). We showed from the changes in the coordinated metal ions that the Cu ion in the Cu-binding site is the catalytic site of the pro-oxidant activity, and a redox-active metal ion in the Zn-binding site has the auxiliary function to enhance the pro-oxidant activity. The auxiliary function is suggested to arise from the intramolecular electron transfer between the coordinated metal ions in the denatured SOD1. The oxidation/reduction cycle of Cu in the Cu-binding site is assisted with changing the oxidation state of a metal ion in the Zn-binding site. The magnitude of the toxicity of the denatured SOD1 is discussed based on the ability of the auxiliary function.", "classifications": [ { "id": "Nakabayashi", "label": "Group Nakabayashi", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Takumi", "last_name": "Ohyama", "name": null }, { "creator_type": "author", "first_name": "Kunisato", "last_name": "Kuroi", "name": null }, { "creator_type": "author", "first_name": "Taiyu", "last_name": "Wakabayashi", "name": null }, { "creator_type": "author", "first_name": "Nobuhiro", "last_name": "Fujimaki", "name": null }, { "creator_type": "author", "first_name": "Takakazu", "last_name": "Nakabayashi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/acs.jpcb.9b11807" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "32101437" } }, "mesh": [ { "descriptor": "Amyotrophic Lateral Sclerosis", "descriptor_ui": "D000690", "major_topic": true }, { "descriptor": "Electrons", "descriptor_ui": "D004583", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Ions", "descriptor_ui": "D007477", "major_topic": false }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": false }, { "descriptor": "Oxidation-Reduction", "descriptor_ui": "D010084", "major_topic": false }, { "descriptor": "Oxidative Stress", "descriptor_ui": "D018384", "major_topic": false }, { "descriptor": "Superoxide Dismutase", "descriptor_ui": "D013482", "major_topic": false }, { "descriptor": "Superoxide Dismutase-1", "descriptor_ui": "D000072105", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020 Mar 19", "date_precision": "day", "issue": "11", "normalized_date": "2020-03-19", "pages": "2116-2123", "proceedings_title": null, "publisher": "", "title": "The journal of physical chemistry. B", "volume": "124", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Enhancement of Oxidative Reaction by the Intramolecular Electron Transfer between the Coordinated Redox-Active Metal Ions in SOD1.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Lung cancer is diagnosed at an advanced stage due to its unrecognized symptoms, resulting in high mortality. In recent decades, research into the development of an early diagnostic method for lung cancer has expanded in order to overcome the high mortality rate. Calpain 2 (CAPN2) has been suggested as a tumor marker linked to angiogenesis, cell proliferation, and migration in non-small cell lung cancer. In this study, CAPN2 enzyme-activatable near-infrared peptide sensor linked to human serum albumin (HSA-CAPN2) was developed. Intracellular localization and strong recovered fluorescence signals of HSA-CAPN2 were observed in in vitro experiments using A549-Luc cells, and signal recovery was inhibited by ALLN (a CAPN2 inhibitor). In vivo distribution and signal recovery evaluations performed using A549-Luc cell xenograft mice revealed that HSA-CAPN2 accumulated in the tumor region and produced high fluorescent signal recovery. Three-dimensional reconstructed images using single-plane illumination microscopy after tissue clarity visualized localization of HSA-CAPN2 in tumors. In addition, ALLN pretreatment showed a significant inhibitory effect on signal recovery of HSA-CAPN2, and that inhibition was induced by downregulation of CAPN2 at the gene and protein levels followed by decreases in Ca(2+) levels. Overall, the results demonstrate the potential of HSA-CAPN2 as a sensor for CAPN2-enriched cancer.", "classifications": [ { "id": "Higaki", "label": "Group Higaki", "parent": "Ueda", "type": "group" }, { "id": "Ueda", "label": "Team Ueda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Seung-Hae", "last_name": "Kwon", "name": null }, { "creator_type": "author", "first_name": "Taemin", "last_name": "Wi", "name": null }, { "creator_type": "author", "first_name": "Yong Il", "last_name": "Park", "name": null }, { "creator_type": "author", "first_name": "Min Woo", "last_name": "Kim", "name": null }, { "creator_type": "author", "first_name": "Gibok", "last_name": "Lee", "name": null }, { "creator_type": "author", "first_name": "Takumi", "last_name": "Higaki", "name": null }, { "creator_type": "author", "first_name": "Jung Hoon", "last_name": "Choi", "name": null }, { "creator_type": "author", "first_name": "Ruda", "last_name": "Lee", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/acs.bioconjchem.9b00870" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "32069035" } }, "mesh": [ { "descriptor": "A549 Cells", "descriptor_ui": "D000072283", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Biomarkers, Tumor", "descriptor_ui": "D014408", "major_topic": false }, { "descriptor": "Biosensing Techniques", "descriptor_ui": "D015374", "major_topic": false }, { "descriptor": "Calpain", "descriptor_ui": "D002154", "major_topic": false }, { "descriptor": "Carcinoma, Non-Small-Cell Lung", "descriptor_ui": "D002289", "major_topic": false }, { "descriptor": "Cell Transformation, Neoplastic", "descriptor_ui": "D002471", "major_topic": false }, { "descriptor": "Early Detection of Cancer", "descriptor_ui": "D055088", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Lung Neoplasms", "descriptor_ui": "D008175", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Nanotechnology", "descriptor_ui": "D036103", "major_topic": false }, { "descriptor": "Optical Imaging", "descriptor_ui": "D061848", "major_topic": false }, { "descriptor": "Serum Albumin, Human", "descriptor_ui": "D000075462", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020 Mar 18", "date_precision": "day", "issue": "3", "normalized_date": "2020-03-18", "pages": "803-812", "proceedings_title": null, "publisher": "", "title": "Bioconjugate chemistry", "volume": "31", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Noninvasive Early Detection of Calpain 2-Enriched Non-Small Cell Lung Cancer Using a Human Serum Albumin-Bounded Calpain 2 Nanosensor.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Despite extensive study, the morphogenetic mechanisms of heart looping remain controversial because of a lack of information concerning precise tissue-level deformation and the quantitative relationship between tissue and cellular dynamics; this lack of information causes difficulties in evaluating previously proposed models. To overcome these limitations, we perform four-dimensional (4D) high-resolution imaging to reconstruct a tissue deformation map, which reveals that, at the tissue scale, initial heart looping is achieved by left-right (LR) asymmetry in the direction of deformation within the myocardial tube. We further identify F-actin-dependent directional cell rearrangement in the right myocardium as a major contributor to LR asymmetric tissue deformation. Our findings demonstrate that heart looping involves dynamic and intrinsic cellular behaviors within the tubular tissue and provide a significantly different viewpoint from current models that are based on LR asymmetry of growth and/or stress at the tube boundaries. Finally, we propose a minimally sufficient model for initial heart looping that is also supported by mechanical simulations.", "classifications": [ { "id": "Morishita", "label": "Group Morishita", "parent": "Morishita", "type": "group" }, { "id": "Morishita", "label": "Team Morishita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Naofumi", "last_name": "Kawahira", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Ohtsuka", "name": null }, { "creator_type": "author", "first_name": "Naoki", "last_name": "Kida", "name": null }, { "creator_type": "author", "first_name": "Ken-Ichi", "last_name": "Hironaka", "name": null }, { "creator_type": "author", "first_name": "Yoshihiro", "last_name": "Morishita", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.celrep.2020.02.071" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "32187557" } }, "mesh": [ { "descriptor": "Actins", "descriptor_ui": "D000199", "major_topic": false }, { "descriptor": "Anatomic Landmarks", "descriptor_ui": "D059925", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Anisotropy", "descriptor_ui": "D016880", "major_topic": false }, { "descriptor": "Body Patterning", "descriptor_ui": "D019521", "major_topic": false }, { "descriptor": "Cell Division", "descriptor_ui": "D002455", "major_topic": false }, { "descriptor": "Cell Shape", "descriptor_ui": "D048430", "major_topic": false }, { "descriptor": "Cell Size", "descriptor_ui": "D048429", "major_topic": false }, { "descriptor": "Chickens", "descriptor_ui": "D002645", "major_topic": false }, { "descriptor": "Computer Simulation", "descriptor_ui": "D003198", "major_topic": false }, { "descriptor": "Heart", "descriptor_ui": "D006321", "major_topic": false }, { "descriptor": "Imaging, Three-Dimensional", "descriptor_ui": "D021621", "major_topic": true }, { "descriptor": "Models, Anatomic", "descriptor_ui": "D008953", "major_topic": false }, { "descriptor": "Myocardium", "descriptor_ui": "D009206", "major_topic": false }, { "descriptor": "Polymerization", "descriptor_ui": "D058105", "major_topic": false }, { "descriptor": "Stress, Mechanical", "descriptor_ui": "D013314", "major_topic": true }, { "descriptor": "Time-Lapse Imaging", "descriptor_ui": "D059008", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020 Mar 17", "date_precision": "day", "issue": "11", "normalized_date": "2020-03-17", "pages": "3889-3903.e5", "proceedings_title": null, "publisher": "", "title": "Cell reports", "volume": "30", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Quantitative Analysis of 3D Tissue Deformation Reveals Key Cellular Mechanism Associated with Initial Heart Looping.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "In vitro reconstitution of germ-cell development from pluripotent stem cells (PSCs) has created key opportunities to explore the fundamental mechanisms underlying germ-cell development, particularly in mice and humans. Importantly, such investigations have clarified critical species differences in the mechanisms regulating mouse and human germ-cell development, highlighting the necessity of establishing an in vitro germ-cell development system in other mammals, such as non-human primates. Here, we show that multiple lines of embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) in cynomolgus monkeys (Macaca fascicularis; cy) can be maintained stably in an undifferentiated state under a defined condition with an inhibitor for WNT signaling, and such PSCs are induced efficiently into primordial germ cell-like cells (PGCLCs) bearing a transcriptome similar to early cyPGCs. Interestingly, the induction kinetics of cyPGCLCs from cyPSCs is faster than that of human (h) PGCLCs from hPSCs, and while the transcriptome dynamics during cyPGCLC induction is relatively similar to that during hPGCLC induction, it is substantially divergent from that during mouse (m) PGCLC induction. Our findings delineate common as well as species-specific traits for PGC specification, creating a foundation for parallel investigations into the mechanism for germ-cell development in mice, monkeys, and humans.", "classifications": [ { "id": "Yamamoto", "label": "Group Yamamoto", "parent": "Toyoshima", "type": "group" }, { "id": "Toyoshima", "label": "Team Toyoshima", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yoshitake", "last_name": "Sakai", "name": null }, { "creator_type": "author", "first_name": "Tomonori", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Ikuhiro", "last_name": "Okamoto", "name": null }, { "creator_type": "author", "first_name": "Sayuri", "last_name": "Gyobu-Motani", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Ohta", "name": null }, { "creator_type": "author", "first_name": "Yukihiro", "last_name": "Yabuta", "name": null }, { "creator_type": "author", "first_name": "Tomoyuki", "last_name": "Tsukiyama", "name": null }, { "creator_type": "author", "first_name": "Chiduru", "last_name": "Iwatani", "name": null }, { "creator_type": "author", "first_name": "Hideaki", "last_name": "Tsuchiya", "name": null }, { "creator_type": "author", "first_name": "Masatsugu", "last_name": "Ema", "name": null }, { "creator_type": "author", "first_name": "Asuka", "last_name": "Morizane", "name": null }, { "creator_type": "author", "first_name": "Jun", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Mitinori", "last_name": "Saitou", "name": null } ], "identifiers": { "doi": { "normalized": "10.1093/biolre/ioz205" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "31724030" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Induced Pluripotent Stem Cells", "descriptor_ui": "D057026", "major_topic": false }, { "descriptor": "Macaca fascicularis", "descriptor_ui": "D008252", "major_topic": false }, { "descriptor": "Pluripotent Stem Cells", "descriptor_ui": "D039904", "major_topic": false }, { "descriptor": "Transcriptome", "descriptor_ui": "D059467", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020 Mar 13", "date_precision": "day", "issue": "3", "normalized_date": "2020-03-13", "pages": "620-638", "proceedings_title": null, "publisher": "", "title": "Biology of reproduction", "volume": "102", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Induction of the germ cell fate from pluripotent stem cells in cynomolgus monkeysdagger.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Distinct components of working memory are coordinated by different classes of inhibitory interneurons in the PFC, but the role of cholecystokinin (CCK)-positive interneurons remains enigmatic. In humans, this major population of interneurons shows histological abnormalities in schizophrenia, an illness in which deficient working memory is a core defining symptom and the best predictor of long-term functional outcome. Yet, CCK interneurons as a molecularly distinct class have proved intractable to examination by typical molecular methods due to widespread expression of CCK in the pyramidal neuron population. Using an intersectional approach in mice of both sexes, we have succeeded in labeling, interrogating, and manipulating CCK interneurons in the mPFC. Here, we describe the anatomical distribution, electrophysiological properties, and postsynaptic connectivity of CCK interneurons, and evaluate their role in cognition. We found that CCK interneurons comprise a larger proportion of the mPFC interneurons compared with parvalbumin interneurons, targeting a wide range of neuronal subtypes with a distinct connectivity pattern. Phase-specific optogenetic inhibition revealed that CCK, but not parvalbumin, interneurons play a critical role in the retrieval of working memory. These findings shine new light on the relationship between cortical CCK interneurons and cognition and offer a new set of tools to investigate interneuron dysfunction and cognitive impairments associated with schizophrenia.SIGNIFICANCE STATEMENT Cholecystokinin-expressing interneurons outnumber other interneuron populations in key brain areas involved in cognition and memory, including the mPFC. However, they have proved intractable to examination as experimental techniques have lacked the necessary selectivity. To the best of our knowledge, the present study is the first to report detailed properties of cortical cholecystokinin interneurons, revealing their anatomical organization, electrophysiological properties, postsynaptic connectivity, and behavioral function in working memory.", "classifications": [ { "id": "Imayoshi", "label": "Group Imayoshi", "parent": "Imayoshi", "type": "group" }, { "id": "Imayoshi", "label": "Team Imayoshi", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Robin", "last_name": "Nguyen", "name": null }, { "creator_type": "author", "first_name": "Sridevi", "last_name": "Venkatesan", "name": null }, { "creator_type": "author", "first_name": "Mary", "last_name": "Binko", "name": null }, { "creator_type": "author", "first_name": "Jee Yoon", "last_name": "Bang", "name": null }, { "creator_type": "author", "first_name": "Janine D.", "last_name": "Cajanding", "name": null }, { "creator_type": "author", "first_name": "Chloe", "last_name": "Briggs", "name": null }, { "creator_type": "author", "first_name": "Derya", "last_name": "Sargin", "name": null }, { "creator_type": "author", "first_name": "Itaru", "last_name": "Imayoshi", "name": null }, { "creator_type": "author", "first_name": "Evelyn K.", "last_name": "Lambe", "name": null }, { "creator_type": "author", "first_name": "Jun Chul", "last_name": "Kim", "name": null } ], "identifiers": { "doi": { "normalized": "10.1523/jneurosci.1919-19.2020" }, "pmcid": { "normalized": "PMC7083295" }, "pmid": { "normalized": "32005764" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Appetitive Behavior", "descriptor_ui": "D001070", "major_topic": false }, { "descriptor": "Cholecystokinin", "descriptor_ui": "D002766", "major_topic": false }, { "descriptor": "Discrimination Learning", "descriptor_ui": "D004193", "major_topic": false }, { "descriptor": "Discrimination, Psychological", "descriptor_ui": "D004192", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Genes, Reporter", "descriptor_ui": "D017930", "major_topic": false }, { "descriptor": "Interneurons", "descriptor_ui": "D007395", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Memory, Short-Term", "descriptor_ui": "D008570", "major_topic": false }, { "descriptor": "Mental Recall", "descriptor_ui": "D011939", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Transgenic", "descriptor_ui": "D008822", "major_topic": false }, { "descriptor": "Nerve Tissue Proteins", "descriptor_ui": "D009419", "major_topic": false }, { "descriptor": "Odorants", "descriptor_ui": "D009812", "major_topic": false }, { "descriptor": "Optogenetics", "descriptor_ui": "D062308", "major_topic": false }, { "descriptor": "Parvalbumins", "descriptor_ui": "D010320", "major_topic": false }, { "descriptor": "Patch-Clamp Techniques", "descriptor_ui": "D018408", "major_topic": false }, { "descriptor": "Prefrontal Cortex", "descriptor_ui": "D017397", "major_topic": false }, { "descriptor": "Reward", "descriptor_ui": "D012201", "major_topic": false }, { "descriptor": "Schizophrenia", "descriptor_ui": "D012559", "major_topic": false }, { "descriptor": "Smell", "descriptor_ui": "D012903", "major_topic": false }, { "descriptor": "Synaptic Potentials", "descriptor_ui": "D055366", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020 Mar 11", "date_precision": "day", "issue": "11", "normalized_date": "2020-03-11", "pages": "2314-2331", "proceedings_title": null, "publisher": "", "title": "The Journal of neuroscience : the official journal of the Society for Neuroscience", "volume": "40", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Cholecystokinin-Expressing Interneurons of the Medial Prefrontal Cortex Mediate Working Memory Retrieval.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Sex determination of germ cells is vital to creating the sexual dichotomy of germ cell development, thereby ensuring sexual reproduction. However, the underlying mechanisms remain unclear. Here, we show that ZGLP1, a conserved transcriptional regulator with GATA-like zinc fingers, determines the oogenic fate in mice. ZGLP1 acts downstream of bone morphogenetic protein, but not retinoic acid (RA), and is essential for the oogenic program and meiotic entry. ZGLP1 overexpression induces differentiation of in vitro primordial germ cell-like cells (PGCLCs) into fetal oocytes by activating the oogenic programs repressed by Polycomb activities, whereas RA signaling contributes to oogenic program maturation and PGC program repression. Our findings elucidate the mechanism for mammalian oogenic fate determination, providing a foundation for promoting in vitro gametogenesis and reproductive medicine.", "classifications": [ { "id": "Yamamoto", "label": "Group Yamamoto", "parent": "Toyoshima", "type": "group" }, { "id": "Toyoshima", "label": "Team Toyoshima", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "So I.", "last_name": "Nagaoka", "name": null }, { "creator_type": "author", "first_name": "Fumio", "last_name": "Nakaki", "name": null }, { "creator_type": "author", "first_name": "Hidetaka", "last_name": "Miyauchi", "name": null }, { "creator_type": "author", "first_name": "Yoshiaki", "last_name": "Nosaka", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Ohta", "name": null }, { "creator_type": "author", "first_name": "Yukihiro", "last_name": "Yabuta", "name": null }, { "creator_type": "author", "first_name": "Kazuki", "last_name": "Kurimoto", "name": null }, { "creator_type": "author", "first_name": "Katsuhiko", "last_name": "Hayashi", "name": null }, { "creator_type": "author", "first_name": "Tomonori", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Mitinori", "last_name": "Saitou", "name": null } ], "identifiers": { "doi": { "normalized": "10.1126/science.aaw4115" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "32054698" } }, "mesh": [ { "descriptor": "Adaptor Proteins, Signal Transducing", "descriptor_ui": "D048868", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Bone Morphogenetic Proteins", "descriptor_ui": "D019485", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Fetus", "descriptor_ui": "D005333", "major_topic": false }, { "descriptor": "Gene Expression Regulation, Developmental", "descriptor_ui": "D018507", "major_topic": true }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Meiosis", "descriptor_ui": "D008540", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Oocytes", "descriptor_ui": "D009865", "major_topic": false }, { "descriptor": "Oogenesis", "descriptor_ui": "D009866", "major_topic": false }, { "descriptor": "Polycomb-Group Proteins", "descriptor_ui": "D063146", "major_topic": false }, { "descriptor": "Repressor Proteins", "descriptor_ui": "D012097", "major_topic": false }, { "descriptor": "Sex Determination Processes", "descriptor_ui": "D019849", "major_topic": false }, { "descriptor": "Sex Differentiation", "descriptor_ui": "D012733", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Transcription Factors", "descriptor_ui": "D014157", "major_topic": false }, { "descriptor": "Transcriptome", "descriptor_ui": "D059467", "major_topic": false }, { "descriptor": "Tretinoin", "descriptor_ui": "D014212", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020 Mar 6", "date_precision": "day", "issue": "6482", "normalized_date": "2020-03-06", "pages": "eaaw4115", "proceedings_title": null, "publisher": "", "title": "Science (New York, N.Y.)", "volume": "367", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "ZGLP1 is a determinant for the oogenic fate in mice.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The epithelial to mesenchymal transition (EMT) is a cell intrinsic program controlling cellular morphological and phenotypic remodeling in a wide range of biological processes. Despite the accumulating evidence, the transcriptional networks regulating EMT still remain to be elucidated. In this study, we demonstrate that C-terminal binding protein 2 (CtBP2), a critical transcriptional co-repressor harboring pyridine nucleotide sensing capability, orchestrates the EMT program at least in part through a novel transcriptional interaction with an octamer transcription factor, OCT1 (POU2F1, POU class 2 homeobox 1). We identified novel interactions of CtBP2 with several octamer transcription factors, and CtBP2 exhibits a direct interaction with OCT1 in particular. OCT1 accelerates the EMT program as reported, which is diminished by the mutation of the CtBP-binding motif in OCT1, suggesting OCT1 represses epithelial gene expression through recruiting the co-repressor CtBP2. In accordance with these findings, a canonical EMT activator transforming growth factor-beta (TGF-beta) promotes the formation of the CtBP2/OCT1 complex. Our observations illustrate the role of CtBP2 to orchestrate the EMT program through the interaction with OCT1 and highlight the potential of therapeutic exploitation of this new transcriptional system for a wide range of diseases.", "classifications": [ { "id": "Miyamoto", "label": "Group Miyamoto", "parent": "Wakamoto", "type": "group" }, { "id": "Wakamoto", "label": "Team Wakamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yang", "last_name": "Ma", "name": null }, { "creator_type": "author", "first_name": "Motohiro", "last_name": "Sekiya", "name": null }, { "creator_type": "author", "first_name": "Kenta", "last_name": "Kainoh", "name": null }, { "creator_type": "author", "first_name": "Takaaki", "last_name": "Matsuda", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Iwasaki", "name": null }, { "creator_type": "author", "first_name": "Yoshinori", "last_name": "Osaki", "name": null }, { "creator_type": "author", "first_name": "Yoko", "last_name": "Sugano", "name": null }, { "creator_type": "author", "first_name": "Hiroaki", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Yoshinori", "last_name": "Takeuchi", "name": null }, { "creator_type": "author", "first_name": "Takafumi", "last_name": "Miyamoto", "name": null }, { "creator_type": "author", "first_name": "Naoya", "last_name": "Yahagi", "name": null }, { "creator_type": "author", "first_name": "Yoshimi", "last_name": "Nakagawa", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Matsuzaka", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Shimano", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.bbrc.2019.12.070" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "31866012" } }, "mesh": [ { "descriptor": "Alcohol Oxidoreductases", "descriptor_ui": "D000429", "major_topic": false }, { "descriptor": "Amino Acid Sequence", "descriptor_ui": "D000595", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Breast Neoplasms", "descriptor_ui": "D001943", "major_topic": false }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Co-Repressor Proteins", "descriptor_ui": "D056970", "major_topic": false }, { "descriptor": "Conserved Sequence", "descriptor_ui": "D017124", "major_topic": false }, { "descriptor": "Epithelial-Mesenchymal Transition", "descriptor_ui": "D058750", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Gene Regulatory Networks", "descriptor_ui": "D053263", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "MCF-7 Cells", "descriptor_ui": "D061986", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": false }, { "descriptor": "Octamer Transcription Factor-1", "descriptor_ui": "D050811", "major_topic": false }, { "descriptor": "Protein Interaction Domains and Motifs", "descriptor_ui": "D054730", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Transforming Growth Factor beta", "descriptor_ui": "D016212", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020 Mar 5", "date_precision": "day", "issue": "2", "normalized_date": "2020-03-05", "pages": "354-360", "proceedings_title": null, "publisher": "", "title": "Biochemical and biophysical research communications", "volume": "523", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Transcriptional co-repressor CtBP2 orchestrates epithelial-mesenchymal transition through a novel transcriptional holocomplex with OCT1.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: Read coverage of RNA sequencing data reflects gene expression and RNA processing events. Single-cell RNA sequencing (scRNA-seq) methods, particularly \"full-length\" ones, provide read coverage of many individual cells and have the potential to reveal cellular heterogeneity in RNA transcription and processing. However, visualization tools suited to highlighting cell-to-cell heterogeneity in read coverage are still lacking. RESULTS: Here, we have developed Millefy, a tool for visualizing read coverage of scRNA-seq data in genomic contexts. Millefy is designed to show read coverage of all individual cells at once in genomic contexts and to highlight cell-to-cell heterogeneity in read coverage. By visualizing read coverage of all cells as a heat map and dynamically reordering cells based on diffusion maps, Millefy facilitates discovery of \"local\" region-specific, cell-to-cell heterogeneity in read coverage. We applied Millefy to scRNA-seq data sets of mouse embryonic stem cells and triple-negative breast cancers and showed variability of transcribed regions including antisense RNAs, 3 (') UTR lengths, and enhancer RNA transcription. CONCLUSIONS: Millefy simplifies the examination of cellular heterogeneity in RNA transcription and processing events using scRNA-seq data. Millefy is available as an R package (https://github.com/yuifu/millefy) and as a Docker image for use with Jupyter Notebook (https://hub.docker.com/r/yuifu/datascience-notebook-millefy).", "classifications": [ { "id": "Nikaido", "label": "Group Nikaido", "parent": "Fujiwara", "type": "group" }, { "id": "Fujiwara", "label": "Team Fujiwara", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Haruka", "last_name": "Ozaki", "name": null }, { "creator_type": "author", "first_name": "Tetsutaro", "last_name": "Hayashi", "name": null }, { "creator_type": "author", "first_name": "Mana", "last_name": "Umeda", "name": null }, { "creator_type": "author", "first_name": "Itoshi", "last_name": "Nikaido", "name": null } ], "identifiers": { "doi": { "normalized": "10.1186/s12864-020-6542-z" }, "pmcid": { "normalized": "PMC7053140" }, "pmid": { "normalized": "32122302" } }, "mesh": [ { "descriptor": "3' Untranslated Regions", "descriptor_ui": "D020413", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Computational Biology", "descriptor_ui": "D019295", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Gene Expression Profiling", "descriptor_ui": "D020869", "major_topic": false }, { "descriptor": "Genetic Heterogeneity", "descriptor_ui": "D018740", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mouse Embryonic Stem Cells", "descriptor_ui": "D000066450", "major_topic": false }, { "descriptor": "RNA, Antisense", "descriptor_ui": "D016372", "major_topic": false }, { "descriptor": "Sequence Analysis, RNA", "descriptor_ui": "D017423", "major_topic": false }, { "descriptor": "Single-Cell Analysis", "descriptor_ui": "D059010", "major_topic": false }, { "descriptor": "Software", "descriptor_ui": "D012984", "major_topic": false }, { "descriptor": "Triple Negative Breast Neoplasms", "descriptor_ui": "D064726", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020 Mar 3", "date_precision": "day", "issue": "1", "normalized_date": "2020-03-03", "pages": "177", "proceedings_title": null, "publisher": "", "title": "BMC genomics", "volume": "21", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Millefy: visualizing cell-to-cell heterogeneity in read coverage of single-cell RNA sequencing datasets.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Plant growth and development relies on the accurate positioning of the cell plate between dividing cells during cytokinesis. The cell plate is synthetized by a specialized structure called the phragmoplast, which contains bipolar microtubules that polymerize to form a framework with the plus ends at or near the division site. This allows the transport of Golgi-derived vesicles toward the plus ends to form and expand the cell plate. Actin filaments play important roles in cell plate expansion and guidance in plant cytokinesis at the late phase, but whether they are involved at the early phase is unknown. To investigate this further, we disrupted the actin filaments in cell cycle-synchronized tobacco BY-2 cells with latrunculin B (LatB), an actin polymerization inhibitor. We observed the cells under a transmission electron microscope or a spinning-disk confocal laser scanning microscope. We found that disruption of actin filaments by LatB caused the membrane vesicles at the equatorial plane of the cell plate to be dispersed rather than form clusters as they did in the untreated cells. The midzone constriction of phragmoplast microtubules also was perturbed in LatB-treated cells. The live cell imaging and kymograph analysis showed that disruption of actin filaments also changed the accumulation timing of NACK1 kinesin, which plays a crucial role in cell plate expansion. This suggests that there are two functionally different types of microtubules in the phragmoplast. Together, our results show that actin filaments regulate phragmoplast microtubules at the initial phase of plant cytokinesis.", "classifications": [ { "id": "Higaki", "label": "Group Higaki", "parent": "Ueda", "type": "group" }, { "id": "Ueda", "label": "Team Ueda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Keisho", "last_name": "Maeda", "name": null }, { "creator_type": "author", "first_name": "Michiko", "last_name": "Sasabe", "name": null }, { "creator_type": "author", "first_name": "Shigeru", "last_name": "Hanamata", "name": null }, { "creator_type": "author", "first_name": "Yasunori", "last_name": "Machida", "name": null }, { "creator_type": "author", "first_name": "Seiichiro", "last_name": "Hasezawa", "name": null }, { "creator_type": "author", "first_name": "Takumi", "last_name": "Higaki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1093/pcp/pcaa003" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "32030404" } }, "mesh": [ { "descriptor": "Actin Cytoskeleton", "descriptor_ui": "D008841", "major_topic": false }, { "descriptor": "Bridged Bicyclo Compounds, Heterocyclic", "descriptor_ui": "D019086", "major_topic": false }, { "descriptor": "Cell Division", "descriptor_ui": "D002455", "major_topic": false }, { "descriptor": "Cytokinesis", "descriptor_ui": "D048749", "major_topic": false }, { "descriptor": "Cytoplasm", "descriptor_ui": "D003593", "major_topic": false }, { "descriptor": "Kinesins", "descriptor_ui": "D016547", "major_topic": false }, { "descriptor": "Microtubules", "descriptor_ui": "D008870", "major_topic": false }, { "descriptor": "Nicotiana", "descriptor_ui": "D014026", "major_topic": false }, { "descriptor": "Plant Development", "descriptor_ui": "D063245", "major_topic": false }, { "descriptor": "Thiazolidines", "descriptor_ui": "D053778", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020 Mar 1", "date_precision": "day", "issue": "3", "normalized_date": "2020-03-01", "pages": "445-456", "proceedings_title": null, "publisher": "", "title": "Plant & cell physiology", "volume": "61", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Actin Filament Disruption Alters Phragmoplast Microtubule Dynamics during the Initial Phase of Plant Cytokinesis.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "An amendment to this paper has been published and can be accessed via a link at the top of the paper.", "classifications": [ { "id": "Yusa", "label": "Group Yusa", "parent": "Eiraku", "type": "group" }, { "id": "Eiraku", "label": "Team Eiraku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Iris E.", "last_name": "Jansen", "name": null }, { "creator_type": "author", "first_name": "Jeanne E.", "last_name": "Savage", "name": null }, { "creator_type": "author", "first_name": "Kyoko", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Julien", "last_name": "Bryois", "name": null }, { "creator_type": "author", "first_name": "Dylan M.", "last_name": "Williams", "name": null }, { "creator_type": "author", "first_name": "Stacy", "last_name": "Steinberg", "name": null }, { "creator_type": "author", "first_name": "Julia", "last_name": "Sealock", "name": null }, { "creator_type": "author", "first_name": "Ida K.", "last_name": "Karlsson", "name": null }, { "creator_type": "author", "first_name": "Sara", "last_name": "Hägg", "name": null }, { "creator_type": "author", "first_name": "Lavinia", "last_name": "Athanasiu", "name": null }, { "creator_type": "author", "first_name": "Nicola", "last_name": "Voyle", "name": null }, { "creator_type": "author", "first_name": "Petroula", "last_name": "Proitsi", "name": null }, { "creator_type": "author", "first_name": "Aree", "last_name": "Witoelar", "name": null }, { "creator_type": "author", "first_name": "Sven", "last_name": "Stringer", "name": null }, { "creator_type": "author", "first_name": "Dag", "last_name": "Aarsland", "name": null }, { "creator_type": "author", "first_name": "Ina S.", "last_name": "Almdahl", "name": null }, { "creator_type": "author", "first_name": "Fred", "last_name": "Andersen", "name": null }, { "creator_type": "author", "first_name": "Sverre", "last_name": "Bergh", "name": null }, { "creator_type": "author", "first_name": "Francesco", "last_name": "Bettella", "name": null }, { "creator_type": "author", "first_name": "Sigurbjorn", "last_name": "Bjornsson", "name": null }, { "creator_type": "author", "first_name": "Anne", "last_name": "Brækhus", "name": null }, { "creator_type": "author", "first_name": "Geir", "last_name": "Bråthen", "name": null }, { "creator_type": "author", "first_name": "Christiaan", "last_name": "de Leeuw", "name": null }, { "creator_type": "author", "first_name": "Rahul S.", "last_name": "Desikan", "name": null }, { "creator_type": "author", "first_name": "Srdjan", "last_name": "Djurovic", "name": null }, { "creator_type": "author", "first_name": "Logan", "last_name": "Dumitrescu", "name": null }, { "creator_type": "author", "first_name": "Tormod", "last_name": "Fladby", "name": null }, { "creator_type": "author", "first_name": "Timothy J.", "last_name": "Hohman", "name": null }, { "creator_type": "author", "first_name": "Palmi V.", "last_name": "Jonsson", "name": null }, { "creator_type": "author", "first_name": "Steven J.", "last_name": "Kiddle", "name": null }, { "creator_type": "author", "first_name": "Arvid", "last_name": "Rongve", "name": null }, { "creator_type": "author", "first_name": "Ingvild", "last_name": "Saltvedt", "name": null }, { "creator_type": "author", "first_name": "Sigrid B.", "last_name": "Sando", "name": null }, { "creator_type": "author", "first_name": "Geir", "last_name": "Selbæk", "name": null }, { "creator_type": "author", "first_name": "Maryam", "last_name": "Shoai", "name": null }, { "creator_type": "author", "first_name": "Nathan G.", "last_name": "Skene", "name": null }, { "creator_type": "author", "first_name": "Jon", "last_name": "Snaedal", "name": null }, { "creator_type": "author", "first_name": "Eystein", "last_name": "Stordal", "name": null }, { "creator_type": "author", "first_name": "Ingun D.", "last_name": "Ulstein", "name": null }, { "creator_type": "author", "first_name": "Yunpeng", "last_name": "Wang", "name": null }, { "creator_type": "author", "first_name": "Linda R.", "last_name": "White", "name": null }, { "creator_type": "author", "first_name": "John", "last_name": "Hardy", "name": null }, { "creator_type": "author", "first_name": "Jens", "last_name": "Hjerling-Leffler", "name": null }, { "creator_type": "author", "first_name": "Patrick F.", "last_name": "Sullivan", "name": null }, { "creator_type": "author", "first_name": "Wiesje M.", "last_name": "van der Flier", "name": null }, { "creator_type": "author", "first_name": "Richard", "last_name": "Dobson", "name": null }, { "creator_type": "author", "first_name": "Lea K.", "last_name": "Davis", "name": null }, { "creator_type": "author", "first_name": "Hreinn", "last_name": "Stefansson", "name": null }, { "creator_type": "author", "first_name": "Kari", "last_name": "Stefansson", "name": null }, { "creator_type": "author", "first_name": "Nancy L.", "last_name": "Pedersen", "name": null }, { "creator_type": "author", "first_name": "Stephan", "last_name": "Ripke", "name": null }, { "creator_type": "author", "first_name": "Ole A.", "last_name": "Andreassen", "name": null }, { "creator_type": "author", "first_name": "Danielle", "last_name": "Posthuma", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41588-019-0573-x" }, "pmcid": { "normalized": null }, "pmid": { "normalized": null } }, "mesh": [], "publication": { "conference_name": null, "date": "2020-03", "date_precision": "month", "issue": "3", "normalized_date": "2020-03", "pages": "354-354", "proceedings_title": null, "publisher": "Nature Publishing Group", "title": "Nature Genetics", "volume": "52", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Author Correction: Genome-wide meta-analysis identifies new loci and functional pathways influencing Alzheimer’s disease risk", "url": "https://www.nature.com/articles/s41588-019-0573-x", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Metal-organic frameworks with open metal sites are promising materials for gas separations. Particularly, the M(2)(dobdc) (dobdc(4-) = 2,5-dioxidobenzenedicarboxylate, M(2+) = Co(2+), Mn(2+), Fe(2+), ...) framework has been the Drosophila of this research field and has delivered groundbreaking results in terms of sorption selectivity. However, many studies focus on perfect two-component mixtures and use theoretical models, e.g., the ideal adsorbed solution theory, to calculate selectivities. Within this work, we shed light on the comparability of these selectivities with values obtained from propane/propene multicomponent measurements on the prototypical Co(2)(dobdc) framework, and we study the impact of impurities like water on the selectivity. Despite the expected capacity loss, the presence of water does not necessarily lead to a decreased selectivity. Density functional theory calculations of the binding energies prove that the water molecules adsorbed to the metal centers introduce new binding sites for the adsorbates.", "classifications": [ { "id": "Hijikata", "label": "Group Hijikata", "parent": "Tsuchiya", "type": "group" }, { "id": "Tsuchiya", "label": "Team Tsuchiya", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Pia", "last_name": "Vervoorts", "name": null }, { "creator_type": "author", "first_name": "Andreas", "last_name": "Schneemann", "name": null }, { "creator_type": "author", "first_name": "Inke", "last_name": "Hante", "name": null }, { "creator_type": "author", "first_name": "Jenny", "last_name": "Pirillo", "name": null }, { "creator_type": "author", "first_name": "Yuh", "last_name": "Hijikata", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Toyao", "name": null }, { "creator_type": "author", "first_name": "Kenichi", "last_name": "Kon", "name": null }, { "creator_type": "author", "first_name": "Ken-Ichi", "last_name": "Shimizu", "name": null }, { "creator_type": "author", "first_name": "Takayoshi", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Shin-Ichiro", "last_name": "Noro", "name": null }, { "creator_type": "author", "first_name": "Roland A.", "last_name": "Fischer", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/acsami.9b21261" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "31986002" } }, "mesh": [], "publication": { "conference_name": null, "date": "2020 Feb 26", "date_precision": "day", "issue": "8", "normalized_date": "2020-02-26", "pages": "9448-9456", "proceedings_title": null, "publisher": "", "title": "ACS applied materials & interfaces", "volume": "12", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Coordinated Water as New Binding Sites for the Separation of Light Hydrocarbons in Metal-Organic Frameworks with Open Metal Sites.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "An engineered light-inducible chloride pump, Natronomonas pharaonis halorhodopsin 3 (eNpHR3) enables temporally and spatially precise inhibition of genetically defined cell populations in the intact nervous tissues. In this report, we show the generation of new mouse strains that express eNpHR3-EYFP fusion proteins after Cre- and/or Flp-mediated recombination to optically inhibit neuronal activity. In these mouse strains, Cre/Flp recombination induced high levels of opsin expression. We confirmed their light-induced activities by brain slice whole-cell patch clamp experiments. eNpHR3-expressing neurons were optically hyperpolarized and silenced from firing action potentials. In prolonged silencing of action potentials, eNpHR3 was superior to eNpHR2, a former version of the engineered pump. Thus, these eNpHR3 mouse strains offer reliable genetic tools for light-induced inhibiting of neuronal activity in defined sets of neurons.", "classifications": [ { "id": "JPMJCR1921", "label": "JPMJCR1921", "researcher": "Itaru Imayoshi", "type": "grant" }, { "id": "Imayoshi", "label": "Group Imayoshi", "parent": "Imayoshi", "type": "group" }, { "id": "Imayoshi", "label": "Team Imayoshi", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Itaru", "last_name": "Imayoshi", "name": null }, { "creator_type": "author", "first_name": "Sawako", "last_name": "Tabuchi", "name": null }, { "creator_type": "author", "first_name": "Mami", "last_name": "Matsumoto", "name": null }, { "creator_type": "author", "first_name": "Satsuki", "last_name": "Kitano", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Miyachi", "name": null }, { "creator_type": "author", "first_name": "Ryoichiro", "last_name": "Kageyama", "name": null }, { "creator_type": "author", "first_name": "Akihiro", "last_name": "Yamanaka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41598-020-59984-3" }, "pmcid": { "normalized": "PMC7035371" }, "pmid": { "normalized": "32081938" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Chromosomes, Artificial, Bacterial", "descriptor_ui": "D022202", "major_topic": false }, { "descriptor": "GABAergic Neurons", "descriptor_ui": "D059330", "major_topic": false }, { "descriptor": "Gene Knock-In Techniques", "descriptor_ui": "D055879", "major_topic": true }, { "descriptor": "Glutamates", "descriptor_ui": "D005971", "major_topic": false }, { "descriptor": "Halobacteriaceae", "descriptor_ui": "D006216", "major_topic": false }, { "descriptor": "Halorhodopsins", "descriptor_ui": "D025602", "major_topic": false }, { "descriptor": "Integrases", "descriptor_ui": "D019426", "major_topic": false }, { "descriptor": "Light", "descriptor_ui": "D008027", "major_topic": true }, { "descriptor": "Mice, Transgenic", "descriptor_ui": "D008822", "major_topic": false }, { "descriptor": "Neocortex", "descriptor_ui": "D019579", "major_topic": false }, { "descriptor": "Prosencephalon", "descriptor_ui": "D016548", "major_topic": false }, { "descriptor": "RNA, Untranslated", "descriptor_ui": "D022661", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020 Feb 21", "date_precision": "day", "issue": "1", "normalized_date": "2020-02-21", "pages": "3191", "proceedings_title": null, "publisher": "", "title": "Scientific reports", "volume": "10", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Light-induced silencing of neural activity in Rosa26 knock-in and BAC transgenic mice conditionally expressing the microbial halorhodopsin eNpHR3.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Cellular metabolism is dynamic, but quantifying non-steady metabolic fluxes by stable isotope tracers presents unique computational challenges. Here, we developed an efficient (13)C-tracer dynamic metabolic flux analysis (13C-DMFA) framework for modeling central carbon fluxes that vary over time. We used B-splines to generalize the flux parameterization system and to improve the stability of the optimization algorithm. As proof of concept, we investigated how 3T3-L1 cultured adipocytes acutely metabolize glucose in response to insulin. Insulin rapidly stimulates glucose uptake, but intracellular pathways responded with differing speeds and magnitudes. Fluxes in lower glycolysis increased faster than those in upper glycolysis. Glycolysis fluxes rose disproportionally larger and faster than the tricarboxylic acid cycle, with lactate a primary glucose end product. The uncovered array of flux dynamics suggests that glucose catabolism is additionally regulated beyond uptake to help shunt glucose into appropriate pathways. This work demonstrates the value of using dynamic intracellular fluxes to understand metabolic function and pathway regulation.", "classifications": [ { "id": "Kuroda", "label": "Group Kuroda", "parent": "Kuroda", "type": "group" }, { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Lake-Ee", "last_name": "Quek", "name": null }, { "creator_type": "author", "first_name": "James R.", "last_name": "Krycer", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Ohno", "name": null }, { "creator_type": "author", "first_name": "Katsuyuki", "last_name": "Yugi", "name": null }, { "creator_type": "author", "first_name": "Daniel J.", "last_name": "Fazakerley", "name": null }, { "creator_type": "author", "first_name": "Richard", "last_name": "Scalzo", "name": null }, { "creator_type": "author", "first_name": "Sarah D.", "last_name": "Elkington", "name": null }, { "creator_type": "author", "first_name": "Ziwei", "last_name": "Dai", "name": null }, { "creator_type": "author", "first_name": "Akiyoshi", "last_name": "Hirayama", "name": null }, { "creator_type": "author", "first_name": "Satsuki", "last_name": "Ikeda", "name": null }, { "creator_type": "author", "first_name": "Futaba", "last_name": "Shoji", "name": null }, { "creator_type": "author", "first_name": "Kumi", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Jason W.", "last_name": "Locasale", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "David E.", "last_name": "James", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Kuroda", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.isci.2020.100855" }, "pmcid": { "normalized": "PMC7005519" }, "pmid": { "normalized": "32058966" } }, "mesh": [], "publication": { "conference_name": null, "date": "2020 Feb 21", "date_precision": "day", "issue": "2", "normalized_date": "2020-02-21", "pages": "100855", "proceedings_title": null, "publisher": "", "title": "iScience", "volume": "23", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Dynamic (13)C Flux Analysis Captures the Reorganization of Adipocyte Glucose Metabolism in Response to Insulin.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Acquired chemoresistance is a critical issue for advanced bladder cancer patients during long-term treatment. Recent studies reveal that a fraction of tumor cells with enhanced tumor-initiating potential, or cancer stem-like cells (CSCs), may particularly contribute to acquired chemoresistance and recurrence. Thus, CSC characterization will be the first step towards understanding the mechanisms underlying advanced disease. Here we generated long-term patient-derived cancer cells (PDCs) from bladder cancer patient specimens in spheroid culture, which is favorable for CSC enrichment. Pathological features of bladder cancer PDCs and PDC-dependent patient-derived xenografts (PDXs) were basically similar to those of their corresponding patients' specimens. Notably, CSC marker aldehyde dehydrogenase 1A1 (ALDH1A1), a critical enzyme that synthesizes retinoic acid (RA), was abundantly expressed in PDCs. ALDH1A1 inhibitors and shRNAs repressed both PDC proliferation and spheroid formation, whereas all-trans RA could rescue ALDH1A1 shRNA-suppressed spheroid formation. ALDH inhibitor also reduced the in vivo growth of PDC-derived xenografts. ALDH1A1 knockdown study showed that tubulin beta III (TUBB3) was one of the downregulated genes in PDCs. We identified functional RA response elements in TUBB3 promoter, whose transcriptional activities were substantially activated by RA. Clinical survival database reveals that TUBB3 expression may associate with poor prognosis in bladder cancer patients. Moreover, TUBB3 knockdown was sufficient to suppress PDC proliferation and spheroid formation. Taken together, our results indicate that ALDH1A1 and its putative downstream target TUBB3 are overexpressed in bladder cancer, and those molecules could be applied to alternative diagnostic and therapeutic options for advanced disease.", "classifications": [ { "id": "Okamoto", "label": "Group Okamoto", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Takeshi", "last_name": "Namekawa", "name": null }, { "creator_type": "author", "first_name": "Kazuhiro", "last_name": "Ikeda", "name": null }, { "creator_type": "author", "first_name": "Kuniko", "last_name": "Horie-Inoue", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Okamoto", "name": null }, { "creator_type": "author", "first_name": "Tomohiko", "last_name": "Ichikawa", "name": null }, { "creator_type": "author", "first_name": "Akihiro", "last_name": "Yano", "name": null }, { "creator_type": "author", "first_name": "Satoru", "last_name": "Kawakami", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Inoue", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/ijc.32505" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "31187490" } }, "mesh": [ { "descriptor": "Aldehyde Dehydrogenase 1 Family", "descriptor_ui": "D000080924", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Disease Progression", "descriptor_ui": "D018450", "major_topic": false }, { "descriptor": "Down-Regulation", "descriptor_ui": "D015536", "major_topic": false }, { "descriptor": "HEK293 Cells", "descriptor_ui": "D057809", "major_topic": false }, { "descriptor": "Heterografts", "descriptor_ui": "D064593", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Neoplastic Stem Cells", "descriptor_ui": "D014411", "major_topic": false }, { "descriptor": "Retinal Dehydrogenase", "descriptor_ui": "D050697", "major_topic": false }, { "descriptor": "Retinoic Acid Receptor alpha", "descriptor_ui": "D000072482", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Spheroids, Cellular", "descriptor_ui": "D018874", "major_topic": false }, { "descriptor": "Tretinoin", "descriptor_ui": "D014212", "major_topic": false }, { "descriptor": "Tubulin", "descriptor_ui": "D014404", "major_topic": false }, { "descriptor": "Urinary Bladder Neoplasms", "descriptor_ui": "D001749", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020 Feb 15", "date_precision": "day", "issue": "4", "normalized_date": "2020-02-15", "pages": "1099-1113", "proceedings_title": null, "publisher": "", "title": "International journal of cancer", "volume": "146", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "ALDH1A1 in patient-derived bladder cancer spheroids activates retinoic acid signaling leading to TUBB3 overexpression and tumor progression.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The tumor suppressor folliculin (FLCN) suppresses nuclear translocation of TFE3, a master transcription factor for lysosomal biogenesis, via regulation of amino-acid-sensing Rag GTPases. However, the importance of this lysosomal regulation in mammalian physiology remains unclear. Following hematopoietic-lineage-specific Flcn deletion in mice, we found expansion of vacuolated phagocytes that accumulate glycogen in their cytoplasm, phenotypes reminiscent of lysosomal storage disorder (LSD). We report that TFE3 acts in a feedback loop to transcriptionally activate FLCN expression, and FLCN loss disrupts this loop, augmenting TFE3 activity. Tfe3 deletion in Flcn knockout mice reduces the number of phagocytes and ameliorates LSD-like phenotypes. We further reveal that TFE3 stimulates glycogenesis by promoting the expression of glycogenesis genes, including Gys1 and Gyg, upon loss of Flcn. Taken together, we propose that the FLCN-TFE3 feedback loop acts as a rheostat to control lysosome activity and prevents excessive glycogenesis and LSD-like phagocyte activation.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Mitsuhiro", "last_name": "Endoh", "name": null }, { "creator_type": "author", "first_name": "Masaya", "last_name": "Baba", "name": null }, { "creator_type": "author", "first_name": "Tamie", "last_name": "Endoh", "name": null }, { "creator_type": "author", "first_name": "Akiyoshi", "last_name": "Hirayama", "name": null }, { "creator_type": "author", "first_name": "Ayako", "last_name": "Nakamura-Ishizu", "name": null }, { "creator_type": "author", "first_name": "Terumasa", "last_name": "Umemoto", "name": null }, { "creator_type": "author", "first_name": "Michihiro", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Kunio", "last_name": "Nagashima", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Martin", "last_name": "Lang", "name": null }, { "creator_type": "author", "first_name": "Laura S.", "last_name": "Schmidt", "name": null }, { "creator_type": "author", "first_name": "W. Marston", "last_name": "Linehan", "name": null }, { "creator_type": "author", "first_name": "Toshio", "last_name": "Suda", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.celrep.2020.01.042" }, "pmcid": { "normalized": "PMC8459211" }, "pmid": { "normalized": "32049013" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Lysosomes", "descriptor_ui": "D008247", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Phagocytes", "descriptor_ui": "D010586", "major_topic": false }, { "descriptor": "Proto-Oncogene Proteins", "descriptor_ui": "D011518", "major_topic": false }, { "descriptor": "Tumor Suppressor Proteins", "descriptor_ui": "D025521", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020 Feb 11", "date_precision": "day", "issue": "6", "normalized_date": "2020-02-11", "pages": "1823-1834.e5", "proceedings_title": null, "publisher": "", "title": "Cell reports", "volume": "30", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "A FLCN-TFE3 Feedback Loop Prevents Excessive Glycogenesis and Phagocyte Activation by Regulating Lysosome Activity.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The bilateral symmetry of flowers is a striking morphological achievement during floral evolution, providing high adaptation potential for pollinators. The symmetry can appear when floral organ primordia developmentally initiate. Primordia initiation at the ventral and dorsal sides of the floral bud is differentially regulated by several factors, including external organs of the flower and CYCLOIDEA (CYC) gene homologues, which are expressed asymmetrically on the dorso-ventral axis. It remains unclear how these factors control the diversity in the number and bilateral arrangement of floral organs. Here, we propose a mathematical model demonstrating that the relative strength of the dorsal-to-ventral inhibitions and the size of the floral stem cell region (meristem) determines the number and positions of the sepal and petal primordia. The simulations reproduced the diversity of monocots and eudicots, including snapdragon Antirrhinum majus and its cyc mutant, with respect to organ number, arrangement and initiation patterns, which were dependent on the inhibition strength. These theoretical results suggest that diversity in floral symmetry is primarily regulated by the dorso-ventral inhibitory field and meristem size during developmental evolution.", "classifications": [ { "id": "Fujimoto", "label": "Group Fujimoto", "parent": "Ueda", "type": "group" }, { "id": "Ueda", "label": "Team Ueda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Aiko", "last_name": "Nakagawa", "name": null }, { "creator_type": "author", "first_name": "Miho S.", "last_name": "Kitazawa", "name": null }, { "creator_type": "author", "first_name": "Koichi", "last_name": "Fujimoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1242/dev.182907" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "31969326" } }, "mesh": [ { "descriptor": "Adaptation, Physiological", "descriptor_ui": "D000222", "major_topic": false }, { "descriptor": "Antirrhinum", "descriptor_ui": "D032161", "major_topic": false }, { "descriptor": "Arabidopsis", "descriptor_ui": "D017360", "major_topic": false }, { "descriptor": "Arabidopsis Proteins", "descriptor_ui": "D029681", "major_topic": false }, { "descriptor": "Biodiversity", "descriptor_ui": "D044822", "major_topic": false }, { "descriptor": "Body Patterning", "descriptor_ui": "D019521", "major_topic": false }, { "descriptor": "DNA-Binding Proteins", "descriptor_ui": "D004268", "major_topic": false }, { "descriptor": "Evolution, Molecular", "descriptor_ui": "D019143", "major_topic": false }, { "descriptor": "Flowers", "descriptor_ui": "D035264", "major_topic": false }, { "descriptor": "Gene Expression Regulation, Plant", "descriptor_ui": "D018506", "major_topic": false }, { "descriptor": "Genes, Plant", "descriptor_ui": "D017343", "major_topic": false }, { "descriptor": "Meristem", "descriptor_ui": "D018519", "major_topic": false }, { "descriptor": "Models, Theoretical", "descriptor_ui": "D008962", "major_topic": true }, { "descriptor": "Phylogeny", "descriptor_ui": "D010802", "major_topic": false }, { "descriptor": "Plant Proteins", "descriptor_ui": "D010940", "major_topic": false }, { "descriptor": "Transcription Factors", "descriptor_ui": "D014157", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020 Feb 4", "date_precision": "day", "issue": "3", "normalized_date": "2020-02-04", "pages": "dev182907", "proceedings_title": null, "publisher": "", "title": "Development (Cambridge, England)", "volume": "147", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "A design principle for floral organ number and arrangement in flowers with bilateral symmetry.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: Cardiorenal syndrome is a major cause of mortality in patients with chronic kidney disease (CKD). However, the involvement of detrimental humoral mediators in the pathogenesis of cardiorenal syndrome is still controversial. Trimethylamine-N-oxide (TMAO), a hepatic metabolic product of trimethylamine generated from dietary phosphatidylcholine or carnitine derived by the gut microbiota, has been linked directly with progression of cardiovascular disease and renal dysfunction. Thus, targeting TMAO may be a novel strategy for the prevention of cardiovascular disease and chronic kidney disease. METHODS: Linaclotide, a guanylate cyclase C agonist, was administered to adenine-induced renal failure (RF) mice and changes in renal function and levels of gut-derived uremic toxins, as well as the gut microbiota community, were analyzed using metabolomic and metagenomic methods to reveal its cardiorenal effect. RESULTS: Linaclotide decreased the plasma levels of TMAO at a clinically used low dose of 10 mug/kg in the adenine-induced RF mouse model. At a high concentration of 100 mug/kg, linaclotide clearly improved renal function and reduced the levels of various uremic toxins. A reduction in TMAO levels following linaclotide treatment was also observed in a choline-fed pro-atherosclerotic model. Linaclotide ameliorated renal inflammation and fibrosis and cardiac fibrosis, as well as decreased the expression of collagen I, transforming growth factor-beta, galectin-3 (Gal-3) and ST2 genes. Plasma levels of Gal-3 and ST2 were also reduced. Because exposure of cardiomyocytes to TMAO increased fibronectin expression, these data suggest that linaclotide reduced the levels of TMAO and various uremic toxins and may result in not only renal, but also cardiac, fibrosis. F4/80-positive macrophages were abundant in small intestinal crypts in RF mice, and this increased expression was decreased by linaclotide. Reduced colonic claudin-1 levels were also restored by linaclotide, suggesting that linaclotide ameliorated the 'leaky gut' in RF mice. Metagenomic analysis revealed that the microbial order Clostridiales could be responsible for the change in TMAO levels. CONCLUSION: Linaclotide reduced TMAO and uremic toxin levels and could be a powerful tool for the prevention and control of the cardiorenal syndrome by modification of the gut-cardio-renal axis.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Fumika", "last_name": "Nanto-Hara", "name": null }, { "creator_type": "author", "first_name": "Yoshitomi", "last_name": "Kanemitsu", "name": null }, { "creator_type": "author", "first_name": "Shinji", "last_name": "Fukuda", "name": null }, { "creator_type": "author", "first_name": "Koichi", "last_name": "Kikuchi", "name": null }, { "creator_type": "author", "first_name": "Kei", "last_name": "Asaji", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Saigusa", "name": null }, { "creator_type": "author", "first_name": "Tomoyuki", "last_name": "Iwasaki", "name": null }, { "creator_type": "author", "first_name": "Hsin-Jung", "last_name": "Ho", "name": null }, { "creator_type": "author", "first_name": "Eikan", "last_name": "Mishima", "name": null }, { "creator_type": "author", "first_name": "Takehiro", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Chitose", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Tomoya", "last_name": "Tsukimi", "name": null }, { "creator_type": "author", "first_name": "Tetsuro", "last_name": "Matsuhashi", "name": null }, { "creator_type": "author", "first_name": "Yoshitsugu", "last_name": "Oikawa", "name": null }, { "creator_type": "author", "first_name": "Yukako", "last_name": "Akiyama", "name": null }, { "creator_type": "author", "first_name": "Shigeo", "last_name": "Kure", "name": null }, { "creator_type": "author", "first_name": "Yuji", "last_name": "Owada", "name": null }, { "creator_type": "author", "first_name": "Yoshihisa", "last_name": "Tomioka", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Sadayoshi", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Takaaki", "last_name": "Abe", "name": null } ], "identifiers": { "doi": { "normalized": "10.1093/ndt/gfz126" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "31411705" } }, "mesh": [ { "descriptor": "Adenine", "descriptor_ui": "D000225", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cardio-Renal Syndrome", "descriptor_ui": "D059347", "major_topic": false }, { "descriptor": "Disease Models, Animal", "descriptor_ui": "D004195", "major_topic": false }, { "descriptor": "Disease Progression", "descriptor_ui": "D018450", "major_topic": false }, { "descriptor": "Fibrosis", "descriptor_ui": "D005355", "major_topic": false }, { "descriptor": "Gastrointestinal Microbiome", "descriptor_ui": "D000069196", "major_topic": false }, { "descriptor": "Guanylate Cyclase", "descriptor_ui": "D006162", "major_topic": false }, { "descriptor": "Guanylyl Cyclase C Agonists", "descriptor_ui": "D000074268", "major_topic": false }, { "descriptor": "Inflammation", "descriptor_ui": "D007249", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Peptides", "descriptor_ui": "D010455", "major_topic": false }, { "descriptor": "Renal Insufficiency, Chronic", "descriptor_ui": "D051436", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020 Feb 1", "date_precision": "day", "issue": "2", "normalized_date": "2020-02-01", "pages": "250-264", "proceedings_title": null, "publisher": "", "title": "Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association", "volume": "35", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "The guanylate cyclase C agonist linaclotide ameliorates the gut-cardio-renal axis in an adenine-induced mouse model of chronic kidney disease.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "gamma-Lactam derivatives with multiple contiguous stereogenic carbon centers are ubiquitous in physiologically active compounds. The development of straightforward and reliable synthetic routes to such chiral structural motifs in a stereocontrolled manner should thus be of importance. Herein, we report a strategy to construct polycyclic gamma-lactam derivatives that contain more than two contiguous stereogenic centers in an enantioselective as well as atom-economic manner. Moreover, we have achieved the first enantioselective synthesis of strigolactam derivative GR-24, a racemic variant of which is a potential seed germination stimulator and plant-growth regulator. A key of the procedure presented here is a nickel(0)/chiral phosphoramidite-catalyzed asymmetric [2+2+1] carbonylative cycloaddition between readily accessible ene-imines and carbon monoxide, which proceeded enantioselectively to furnish up to 90% ee (>99% ee after recrystallization). The results of mechanistic studies, including the isolation of a chiral heteronickelacycle, support that the enantioselectivity on the two contiguous carbon atoms of the gamma-lactams is determined during the oxidative cyclization on nickel(0).", "classifications": [ { "id": "Tsuchiya", "label": "Group Tsuchiya", "parent": "Tsuchiya", "type": "group" }, { "id": "Tsuchiya", "label": "Team Tsuchiya", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Keita", "last_name": "Ashida", "name": null }, { "creator_type": "author", "first_name": "Yoichi", "last_name": "Hoshimoto", "name": null }, { "creator_type": "author", "first_name": "Norimitsu", "last_name": "Tohnai", "name": null }, { "creator_type": "author", "first_name": "David E.", "last_name": "Scott", "name": null }, { "creator_type": "author", "first_name": "Masato", "last_name": "Ohashi", "name": null }, { "creator_type": "author", "first_name": "Hanae", "last_name": "Imaizumi", "name": null }, { "creator_type": "author", "first_name": "Yuichiro", "last_name": "Tsuchiya", "name": null }, { "creator_type": "author", "first_name": "Sensuke", "last_name": "Ogoshi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/jacs.9b12493" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "31868355" } }, "mesh": [], "publication": { "conference_name": null, "date": "2020 Jan 22", "date_precision": "day", "issue": "3", "normalized_date": "2020-01-22", "pages": "1594-1602", "proceedings_title": null, "publisher": "", "title": "Journal of the American Chemical Society", "volume": "142", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Enantioselective Synthesis of Polycyclic gamma-Lactams with Multiple Chiral Carbon Centers via Ni(0)-Catalyzed Asymmetric Carbonylative Cycloadditions without Stirring.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Disulfide bonds play a fundamental role in controlling the tertiary structure of proteins; the formation or cleavage of some disulfide bonds can switch the structures and/or functions of proteins. Human galectin-1 (hGal-1), which is a lectin protein, exemplifies how both structure and function are changed by disulfide bonds; the structure and sugar-binding ability of hGal-1 are altered by the formation and cleavage of its three intra-molecular disulfide bonds. In the present study, the dynamics of the structural change of hGal-1 by the formation of disulfide bonds were investigated by time-resolved FTIR spectroscopy combined with a modification in which its thiol groups (-SH) were replaced with S-nitrosylated groups (SNO). Photodissociation of NO from SNO in reduced hGal-1 induced disulfide bond formation and transformed it into the oxidised form. The structural change to the oxidised form involved three distinct kinetics with fast (<300 s), middle ( approximately 600 s), and slow ( approximately 6400 s) lifetimes. In an examination of hGal-1 in the lactose-bound form, structural changes owing to the release of substrate lactose were also observed upon disulfide bond formation. The present method using the photodissociation of NO is useful for monitoring the dynamics of structural changes following disulfide formation.", "classifications": [ { "id": "Nakabayashi", "label": "Group Nakabayashi", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Kunisato", "last_name": "Kuroi", "name": null }, { "creator_type": "author", "first_name": "Mana", "last_name": "Kamijo", "name": null }, { "creator_type": "author", "first_name": "Mutsuki", "last_name": "Ueki", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Niwa", "name": null }, { "creator_type": "author", "first_name": "Hirotsugu", "last_name": "Hiramatsu", "name": null }, { "creator_type": "author", "first_name": "Takakazu", "last_name": "Nakabayashi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1039/c9cp04881b" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "31774080" } }, "mesh": [ { "descriptor": "Disulfides", "descriptor_ui": "D004220", "major_topic": false }, { "descriptor": "Galectin 1", "descriptor_ui": "D037483", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Light", "descriptor_ui": "D008027", "major_topic": false }, { "descriptor": "Models, Molecular", "descriptor_ui": "D008958", "major_topic": true }, { "descriptor": "Protein Structure, Tertiary", "descriptor_ui": "D017434", "major_topic": false }, { "descriptor": "Spectroscopy, Fourier Transform Infrared", "descriptor_ui": "D017550", "major_topic": true } ], "publication": { "conference_name": null, "date": "2020 Jan 22", "date_precision": "day", "issue": "3", "normalized_date": "2020-01-22", "pages": "1137-1144", "proceedings_title": null, "publisher": "", "title": "Physical chemistry chemical physics : PCCP", "volume": "22", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Time-resolved FTIR study on the structural switching of human galectin-1 by light-induced disulfide bond formation.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Monoclonal antibodies (mAbs) are attractive therapeutics for treating a wide range of human disorders, and bind to the antigen through their complementarity-determining regions (CDRs). Small stable proteins containing structurally retained CDRs are promising alternatives to mAbs. In this report, we present a method to create such proteins, named fluctuation-regulated affinity proteins (FLAPs). Thirteen graft acceptor (GA) sites that efficiently immobilise the grafted peptide structure were initially selected from six small protein scaffolds by computational identification. Five CDR peptides extracted by binding energy calculations from mAbs against breast cancer marker human epithelial growth factor receptor type 2 (HER2) were then grafted to the selected scaffolds. The combination of five CDR peptides and 13 GA sites in six scaffolds revealed that three of the 65 combinations showed specific binding to HER2 with dissociation constants (KD) of 270-350 nM in biolayer interferometry and 24-65 nM in ELISA. The FLAPs specifically detected HER2-overexpressing cancer cells. Thus, the present strategy is a promising and practical method for developing small antibody mimetics.", "classifications": [ { "id": "Kuchimaru", "label": "Group Kuchimaru", "parent": "Shintaku", "type": "group" }, { "id": "Shintaku", "label": "Team Shintaku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Tetsuya", "last_name": "Kadonosono", "name": null }, { "creator_type": "author", "first_name": "Wanaporn", "last_name": "Yimchuen", "name": null }, { "creator_type": "author", "first_name": "Yumi", "last_name": "Ota", "name": null }, { "creator_type": "author", "first_name": "Kyra", "last_name": "See", "name": null }, { "creator_type": "author", "first_name": "Tadaomi", "last_name": "Furuta", "name": null }, { "creator_type": "author", "first_name": "Tadashi", "last_name": "Shiozawa", "name": null }, { "creator_type": "author", "first_name": "Maika", "last_name": "Kitazawa", "name": null }, { "creator_type": "author", "first_name": "Yu", "last_name": "Goto", "name": null }, { "creator_type": "author", "first_name": "Akash", "last_name": "Patil", "name": null }, { "creator_type": "author", "first_name": "Takahiro", "last_name": "Kuchimaru", "name": null }, { "creator_type": "author", "first_name": "Shinae", "last_name": "Kizaka-Kondoh", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41598-020-57713-4" }, "pmcid": { "normalized": "PMC6972867" }, "pmid": { "normalized": "31964960" } }, "mesh": [ { "descriptor": "Antibodies, Monoclonal", "descriptor_ui": "D000911", "major_topic": false }, { "descriptor": "Antibodies, Monoclonal, Humanized", "descriptor_ui": "D061067", "major_topic": false }, { "descriptor": "Antigens", "descriptor_ui": "D000941", "major_topic": false }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Complementarity Determining Regions", "descriptor_ui": "D022801", "major_topic": false }, { "descriptor": "Drug Design", "descriptor_ui": "D015195", "major_topic": false }, { "descriptor": "Epitopes", "descriptor_ui": "D000939", "major_topic": false }, { "descriptor": "Erb-b2 Receptor Tyrosine Kinases", "descriptor_ui": "D018719", "major_topic": false }, { "descriptor": "HeLa Cells", "descriptor_ui": "D006367", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Molecular Dynamics Simulation", "descriptor_ui": "D056004", "major_topic": false }, { "descriptor": "Protein Engineering", "descriptor_ui": "D015202", "major_topic": false }, { "descriptor": "Recombinant Proteins", "descriptor_ui": "D011994", "major_topic": false }, { "descriptor": "Reproducibility of Results", "descriptor_ui": "D015203", "major_topic": false }, { "descriptor": "Stomach Neoplasms", "descriptor_ui": "D013274", "major_topic": false }, { "descriptor": "Trastuzumab", "descriptor_ui": "D000068878", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020 Jan 21", "date_precision": "day", "issue": "1", "normalized_date": "2020-01-21", "pages": "891", "proceedings_title": null, "publisher": "", "title": "Scientific reports", "volume": "10", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Design Strategy to Create Antibody Mimetics Harbouring Immobilised Complementarity Determining Region Peptides for Practical Use.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Metal-organic frameworks (MOFs) are known as promising adsorbent materials that can recognize gases specifically. In the frameworks, gases favor interacting with specific binding sites such as open metal sites (OMSs), which can consist of various metals and show characteristic adsorption properties. A recently reported framework possessing OMSs of rhodium paddle-wheel (Rh-PW) showed distinct adsorption properties between NO and CO. We investigated theoretically the reasons for stronger NO binding to the Rh-PW and different adsorption amounts between NO and CO using Rh-PW cluster models, as well as the frequently reported Cu-PW for comparison. We also analyzed the cases of CO(2) and N(2), which are often used to probe functions of MOFs. We observed an increase in binding energy of NO at the second adduction of NO. On the basis of energy decomposition analysis, we found that Rh-NO bond formation inducing a trans influence is important for the stronger binding than with CO. Furthermore, we proposed a reason for twice the adsorption amount of NO than CO. The results are consistent with experimental observations, giving us insight into design functions of MOFs by selecting metal species.", "classifications": [ { "id": "Hijikata", "label": "Group Hijikata", "parent": "Tsuchiya", "type": "group" }, { "id": "Tsuchiya", "label": "Team Tsuchiya", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Jenny", "last_name": "Pirillo", "name": null }, { "creator_type": "author", "first_name": "Yuh", "last_name": "Hijikata", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/acs.inorgchem.9b02911" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "31825598" } }, "mesh": [], "publication": { "conference_name": null, "date": "2020 Jan 21", "date_precision": "day", "issue": "2", "normalized_date": "2020-01-21", "pages": "1193-1203", "proceedings_title": null, "publisher": "", "title": "Inorganic chemistry", "volume": "59", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Trans Influence across a Metal-Metal Bond of a Paddle-Wheel Unit on Interaction with Gases in a Metal-Organic Framework.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Principal component analysis (PCA) is an essential method for analyzing single-cell RNA-seq (scRNA-seq) datasets, but for large-scale scRNA-seq datasets, computation time is long and consumes large amounts of memory.", "classifications": [ { "id": "JPMJCR1926", "label": "JPMJCR1926", "researcher": "Hironobu Fujiwara", "type": "grant" }, { "id": "Fujiwara", "label": "Group Fujiwara", "parent": "Fujiwara", "type": "group" }, { "id": "Nikaido", "label": "Group Nikaido", "parent": "Fujiwara", "type": "group" }, { "id": "Fujiwara", "label": "Team Fujiwara", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Koki", "last_name": "Tsuyuzaki", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Kenta", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Itoshi", "last_name": "Nikaido", "name": null } ], "identifiers": { "doi": { "normalized": "10.1186/s13059-019-1900-3" }, "pmcid": { "normalized": null }, "pmid": { "normalized": null } }, "mesh": [], "publication": { "conference_name": null, "date": "2020-01-20", "date_precision": "day", "issue": "1", "normalized_date": "2020-01-20", "pages": "9", "proceedings_title": null, "publisher": "", "title": "Genome Biology", "volume": "21", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Benchmarking principal component analysis for large-scale single-cell RNA-sequencing", "url": "https://doi.org/10.1186/s13059-019-1900-3", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The physical fractionation of cytoplasmic versus nuclear components of cells is a key step for studying the subcellular localization of molecules. The application of an electric field is an emerging method for subcellular fractionation of proteins and nucleic acids from single cells. However, the multibiophysical process that involves electrical lysis of cytoplasmic membranes, electrophoresis, and diffusion of charged molecules remains unclear. Here we study RNA dynamics in single cells during the electrophoretic extraction via a microfluidic system that enables stringent fractionation of the subcellular components leveraging a focused electric field. We identified two distinct kinetics in the extraction of RNA molecules, which were respectively associated with soluble RNA and mitochondrial RNA. We show that the extraction kinetics of soluble RNA is dominated by electrophoresis over diffusion and has a time constant of 0.15 s. Interestingly, the extraction of mitochondrial RNA showed unexpected heterogeneity in the extraction with slower kinetics (3.8 s), while reproducibly resulting in the extraction of 98.9% +/- 2% after 40 s. Together, we uncover that the microfluidic system uniquely offers length bias-free fractionation of RNA molecules for quantitative analysis of correlations among subcellular compartments by exploiting the homogeneous electrophoretic properties of RNA.", "classifications": [ { "id": "Shintaku", "label": "Group Shintaku", "parent": "Shintaku", "type": "group" }, { "id": "Shintaku", "label": "Team Shintaku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Mahmoud N.", "last_name": "Abdelmoez", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Oguchi", "name": null }, { "creator_type": "author", "first_name": "Yuka", "last_name": "Ozaki", "name": null }, { "creator_type": "author", "first_name": "Ryuji", "last_name": "Yokokawa", "name": null }, { "creator_type": "author", "first_name": "Hidetoshi", "last_name": "Kotera", "name": null }, { "creator_type": "author", "first_name": "Hirofumi", "last_name": "Shintaku", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/acs.analchem.9b04739" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "31805233" } }, "mesh": [ { "descriptor": "Cytoplasm", "descriptor_ui": "D003593", "major_topic": false }, { "descriptor": "Electrophoresis, Capillary", "descriptor_ui": "D019075", "major_topic": false }, { "descriptor": "High-Throughput Nucleotide Sequencing", "descriptor_ui": "D059014", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "K562 Cells", "descriptor_ui": "D020014", "major_topic": false }, { "descriptor": "Kinetics", "descriptor_ui": "D007700", "major_topic": false }, { "descriptor": "Microfluidic Analytical Techniques", "descriptor_ui": "D046210", "major_topic": false }, { "descriptor": "RNA", "descriptor_ui": "D012313", "major_topic": false }, { "descriptor": "Single-Cell Analysis", "descriptor_ui": "D059010", "major_topic": true } ], "publication": { "conference_name": null, "date": "2020 Jan 7", "date_precision": "day", "issue": "1", "normalized_date": "2020-01-07", "pages": "1485-1492", "proceedings_title": null, "publisher": "", "title": "Analytical chemistry", "volume": "92", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Distinct Kinetics in Electrophoretic Extraction of Cytoplasmic RNA from Single Cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Adipose tissue is essential for whole-body glucose homeostasis, with a primary role in lipid storage. It has been previously observed that lactate production is also an important metabolic feature of adipocytes, but its relationship to adipose and whole-body glucose disposal remains unclear. Therefore, using a combination of metabolic labeling techniques, here we closely examined lactate production of cultured and primary mammalian adipocytes. Insulin treatment increased glucose uptake and conversion to lactate, with the latter responding more to insulin than did other metabolic fates of glucose. However, lactate production did not just serve as a mechanism to dispose of excess glucose, because we also observed that lactate production in adipocytes did not solely depend on glucose availability and even occurred independently of glucose metabolism. This suggests that lactate production is prioritized in adipocytes. Furthermore, knocking down lactate dehydrogenase specifically in the fat body of Drosophila flies lowered circulating lactate and improved whole-body glucose disposal. These results emphasize that lactate production is an additional metabolic role of adipose tissue beyond lipid storage and release.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "James R.", "last_name": "Krycer", "name": null }, { "creator_type": "author", "first_name": "Lake-Ee", "last_name": "Quek", "name": null }, { "creator_type": "author", "first_name": "Deanne", "last_name": "Francis", "name": null }, { "creator_type": "author", "first_name": "Daniel J.", "last_name": "Fazakerley", "name": null }, { "creator_type": "author", "first_name": "Sarah D.", "last_name": "Elkington", "name": null }, { "creator_type": "author", "first_name": "Alexis", "last_name": "Diaz-Vegas", "name": null }, { "creator_type": "author", "first_name": "Kristen C.", "last_name": "Cooke", "name": null }, { "creator_type": "author", "first_name": "Fiona C.", "last_name": "Weiss", "name": null }, { "creator_type": "author", "first_name": "Xiaowen", "last_name": "Duan", "name": null }, { "creator_type": "author", "first_name": "Sergey", "last_name": "Kurdyukov", "name": null }, { "creator_type": "author", "first_name": "Ping-Xin", "last_name": "Zhou", "name": null }, { "creator_type": "author", "first_name": "Uttam K.", "last_name": "Tambar", "name": null }, { "creator_type": "author", "first_name": "Akiyoshi", "last_name": "Hirayama", "name": null }, { "creator_type": "author", "first_name": "Satsuki", "last_name": "Ikeda", "name": null }, { "creator_type": "author", "first_name": "Yushi", "last_name": "Kamei", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Gregory J.", "last_name": "Cooney", "name": null }, { "creator_type": "author", "first_name": "David E.", "last_name": "James", "name": null } ], "identifiers": { "doi": { "normalized": "10.1074/jbc.ra119.011178" }, "pmcid": { "normalized": "PMC6952601" }, "pmid": { "normalized": "31690627" } }, "mesh": [ { "descriptor": "3T3 Cells", "descriptor_ui": "D016475", "major_topic": false }, { "descriptor": "Adipocytes", "descriptor_ui": "D017667", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Drosophila", "descriptor_ui": "D004330", "major_topic": false }, { "descriptor": "Fat Body", "descriptor_ui": "D005216", "major_topic": false }, { "descriptor": "Glucose", "descriptor_ui": "D005947", "major_topic": false }, { "descriptor": "Homeostasis", "descriptor_ui": "D006706", "major_topic": true }, { "descriptor": "Insulin", "descriptor_ui": "D007328", "major_topic": false }, { "descriptor": "Lactic Acid", "descriptor_ui": "D019344", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Rats, Sprague-Dawley", "descriptor_ui": "D017207", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020 Jan 3", "date_precision": "day", "issue": "1", "normalized_date": "2020-01-03", "pages": "83-98", "proceedings_title": null, "publisher": "", "title": "The Journal of biological chemistry", "volume": "295", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Lactate production is a prioritized feature of adipocyte metabolism.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Aims: Under hypoxic conditions, nitrite (NO2−) can be reduced to nitric oxide (NO) eliciting vasorelaxation. However, nitrite also exerts vasorelaxant effects of potential therapeutic relevance under normal physiological conditions via undetermined mechanisms. We, therefore, sought to investigate the mechanism(s) by which nitrite regulates the vascular system in normoxia and, specifically, whether the biological effects are a result of NO generation (as in hypoxia) or mediated via alternative mechanisms involving classical downstream targets of NO [e.g. effects on protein kinase G1α (PKG1α)]. Methods and results: Ex vivo myography revealed that, unlike in thoracic aorta (conduit vessels), the vasorelaxant effects of nitrite in mesenteric resistance vessels from wild-type (WT) mice were NO-independent. Oxidants such as H2O2 promote disulfide formation of PKG1α, resulting in NO- cyclic guanosine monophosphate (cGMP) independent kinase activation. To explore whether the microvascular effects of nitrite were associated with PKG1α oxidation, we used a Cys42Ser PKG1α knock-in (C42S PKG1α KI; ‘redox-dead’) mouse that cannot transduce oxidant signals. Resistance vessels from these C42S PKG1α KI mice were markedly less responsive to nitrite-induced vasodilation. Intraperitoneal (i.p.) bolus application of nitrite in conscious WT mice induced a rapid yet transient increase in plasma nitrite and cGMP concentrations followed by prolonged hypotensive effects, as assessed using in vivo telemetry. In the C42S PKG1α KI mice, the blood pressure lowering effects of nitrite were lower compared to WT. Increased H2O2 concentrations were detected in WT resistance vessel tissue challenged with nitrite. Consistent with this, increased cysteine and glutathione persulfide levels were detected in these vessels by mass spectrometry, matching the temporal profile of nitrite’s effects on H2O2 and blood pressure. Conclusion: Under physiological conditions, nitrite induces a delayed and long-lasting blood pressure lowering effect, which is NO-independent and occurs via a new redox mechanism involving H2O2, persulfides, and PKG1α oxidation/activation. Targeting this novel pathway may provide new prospects for anti-hypertensive therapy.", "classifications": [ { "id": "Akaike", "label": "Group Akaike", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Martin", "last_name": "Feelisch", "name": null }, { "creator_type": "author", "first_name": "Takaaki", "last_name": "Akaike", "name": null }, { "creator_type": "author", "first_name": "Kayleigh", "last_name": "Griffiths", "name": null }, { "creator_type": "author", "first_name": "Tomoaki", "last_name": "Ida", "name": null }, { "creator_type": "author", "first_name": "Oleksandra", "last_name": "Prysyazhna", "name": null }, { "creator_type": "author", "first_name": "Joanna J.", "last_name": "Goodwin", "name": null }, { "creator_type": "author", "first_name": "Nicholas D.", "last_name": "Gollop", "name": null }, { "creator_type": "author", "first_name": "Bernadette O.", "last_name": "Fernandez", "name": null }, { "creator_type": "author", "first_name": "Magdalena", "last_name": "Minnion", "name": null }, { "creator_type": "author", "first_name": "Miriam M.", "last_name": "Cortese-Krott", "name": null }, { "creator_type": "author", "first_name": "Alessandra", "last_name": "Borgognone", "name": null }, { "creator_type": "author", "first_name": "Rosie M.", "last_name": "Hayes", "name": null }, { "creator_type": "author", "first_name": "Philip", "last_name": "Eaton", "name": null }, { "creator_type": "author", "first_name": "Michael P.", "last_name": "Frenneaux", "name": null }, { "creator_type": "author", "first_name": "Melanie", "last_name": "Madhani", "name": null } ], "identifiers": { "doi": { "normalized": "10.1093/cvr/cvz202" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "31372656" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Aorta, Thoracic", "descriptor_ui": "D001013", "major_topic": false }, { "descriptor": "Blood Pressure", "descriptor_ui": "D001794", "major_topic": false }, { "descriptor": "Cyclic GMP-Dependent Protein Kinase Type I", "descriptor_ui": "D062965", "major_topic": false }, { "descriptor": "Hydrogen Peroxide", "descriptor_ui": "D006861", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mesenteric Arteries", "descriptor_ui": "D008638", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Nitric Oxide", "descriptor_ui": "D009569", "major_topic": false }, { "descriptor": "Oxidation-Reduction", "descriptor_ui": "D010084", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Sodium Nitrite", "descriptor_ui": "D012977", "major_topic": false }, { "descriptor": "Sulfides", "descriptor_ui": "D013440", "major_topic": false }, { "descriptor": "Vasodilation", "descriptor_ui": "D014664", "major_topic": false }, { "descriptor": "Vasodilator Agents", "descriptor_ui": "D014665", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020 Jan 01", "date_precision": "day", "issue": "1", "normalized_date": "2020-01-01", "pages": "51-62", "proceedings_title": null, "publisher": "", "title": "Cardiovascular Research", "volume": "116", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Long-lasting blood pressure lowering effects of nitrite are NO-independent and mediated by hydrogen peroxide, persulfides, and oxidation of protein kinase G1α redox signalling.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "During the life cycle of flowering plants, nuclear fusion, or karyogamy, occurs three times: once during female gametogenesis, when the two polar nuclei fuse in the central cell, and twice during double fertilization. In Arabidopsis thaliana, nuclear fusion events during sexual reproduction proceed without the breakdown of the nuclear envelope, indicating that nuclear membrane fusion is essential for the completion of this process. Arabidopsis gamete expressed 1 (GEX1) is a membrane protein that is conserved among plant species. GEX1 shares homology with the yeast karyogamy protein Kar5, which is primarily expressed in the nuclear membrane. The GEX1 family represents a putative karyogamy factor. Herein, we show that GEX1 is required for the nuclear fusion events in Arabidopsis reproduction. GEX1-deficient mature female gametophytes were found to contain two unfused polar nuclei in close proximity within the central cell. Electron microscopy showed that the outer membrane of the polar nuclei was connected via the endoplasmic reticulum, whereas the inner membrane remained unfused. These results indicate that GEX1 is involved in polar nuclear membrane fusion following the fusion of the outer nuclear membrane. Furthermore, sperm nuclear fusion events were defective in the fertilized egg and central cell following plasmogamy in the fertilization of gex1-1 female gametophytes by gex1-1 pollen. An analysis of GEX1 localization in the female gametophyte using a transgenic line expressing GFP-tagged GEX1 driven by the GEX1 promoter showed that GEX1 is a nuclear membrane protein in the egg and central cell. Time-lapse live-cell imaging showed that in developing female gametophytes, the nuclear GFP-GEX1 signal was first detectable in the central cell shortly before the polar nuclei came in close contact, and then in the egg cell. Thus, we suggest that the GEX1-family proteins are nuclear membrane proteins involved in karyogamy in the reproduction of eukaryotes including flowering plants.", "classifications": [ { "id": "Sato", "label": "Group Sato", "parent": "Tsuchiya", "type": "group" }, { "id": "Tsuchiya", "label": "Team Tsuchiya", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Shuh-Ichi", "last_name": "Nishikawa", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Yamaguchi", "name": null }, { "creator_type": "author", "first_name": "Chiharu", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Ayaka", "last_name": "Yabe", "name": null }, { "creator_type": "author", "first_name": "Yuzuru", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Kurihara", "name": null }, { "creator_type": "author", "first_name": "Yoshikatsu", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Daichi", "last_name": "Susaki", "name": null }, { "creator_type": "author", "first_name": "Tetsuya", "last_name": "Higashiyama", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Maruyama", "name": null } ], "identifiers": { "doi": { "normalized": "10.3389/fpls.2020.548032" }, "pmcid": { "normalized": "PMC7586128" }, "pmid": { "normalized": "33154760" } }, "mesh": [], "publication": { "conference_name": null, "date": "2020", "date_precision": "year", "issue": "", "normalized_date": "2020", "pages": "548032", "proceedings_title": null, "publisher": "", "title": "Frontiers in plant science", "volume": "11", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Arabidopsis GEX1 Is a Nuclear Membrane Protein of Gametes Required for Nuclear Fusion During Reproduction.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "A 46-year-old man who had previously undergone open surgery for renal cell carcinoma (RCC) developed Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph-ALL). After the induction therapy, he achieved complete molecular remission. However, fever and bilateral buttock pain continued during the consolidation therapy. 18F-fluorodeoxyglucose (FDG) positron emission tomography-computed tomography (PET-CT) showed FDG accumulation in both iliac bones and in the sacrum; however, no causative diseases, including relapse of Ph-ALL and RCC, were detected. Iliac bone marrow biopsy revealed bone marrow necrosis (BMN), the etiology of which was presumed to be the leukemia itself and the therapeutic response to chemotherapy. Fever resolution and buttock pain alleviation were observed over the next months. We observed diffuse fibrosis in the bone marrow at day 162 and day 364 after cord blood transplantation. Moreover, the FDG accumulation was significantly reduced on PET-CT. BMN is not widely recognized despite its potential association with hematologic malignancies. Additional cases of BMN should be reviewed to clarify BMN etiology and clinical features.", "classifications": [ { "id": "Nishikii", "label": "Group Nishikii", "parent": "Shintaku", "type": "group" }, { "id": "Shintaku", "label": "Team Shintaku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Kantaro", "last_name": "Ishitsuka", "name": null }, { "creator_type": "author", "first_name": "Naoshi", "last_name": "Obara", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Suyama", "name": null }, { "creator_type": "author", "first_name": "Ryota", "last_name": "Matsuoka", "name": null }, { "creator_type": "author", "first_name": "Yumiko", "last_name": "Maruyama", "name": null }, { "creator_type": "author", "first_name": "Tatsuhiro", "last_name": "Sakamoto", "name": null }, { "creator_type": "author", "first_name": "Manabu", "last_name": "Kusakabe", "name": null }, { "creator_type": "author", "first_name": "Takayasu", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Naoki", "last_name": "Kurita", "name": null }, { "creator_type": "author", "first_name": "Hidekazu", "last_name": "Nishikii", "name": null }, { "creator_type": "author", "first_name": "Yasuhisa", "last_name": "Yokoyama", "name": null }, { "creator_type": "author", "first_name": "Mamiko", "last_name": "Sakata-Yanagimoto", "name": null }, { "creator_type": "author", "first_name": "Yuichi", "last_name": "Hasegawa", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Shinagawa", "name": null }, { "creator_type": "author", "first_name": "Shigeru", "last_name": "Chiba", "name": null } ], "identifiers": { "doi": { "normalized": "10.11406/rinketsu.61.462" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "32507809" } }, "mesh": [ { "descriptor": "Bone Marrow", "descriptor_ui": "D001853", "major_topic": false }, { "descriptor": "Consolidation Chemotherapy", "descriptor_ui": "D060830", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Philadelphia Chromosome", "descriptor_ui": "D010677", "major_topic": true }, { "descriptor": "Positron Emission Tomography Computed Tomography", "descriptor_ui": "D000072078", "major_topic": false }, { "descriptor": "Precursor Cell Lymphoblastic Leukemia-Lymphoma", "descriptor_ui": "D054198", "major_topic": true } ], "publication": { "conference_name": null, "date": "2020", "date_precision": "year", "issue": "5", "normalized_date": "2020", "pages": "462-467", "proceedings_title": null, "publisher": "", "title": "[Rinsho ketsueki] The Japanese journal of clinical hematology", "volume": "61", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "[Philadelphia chromosome-positive acute lymphoblastic leukemia complicated by bone marrow necrosis during consolidation chemotherapy].", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Tracheal cartilage provides architectural integrity to the respiratory airway, and defects in this structure during embryonic development cause severe congenital anomalies. Previous genetic studies have revealed genes that are critical for the development of tracheal cartilage. However, it is still unclear how crosstalk between these proteins regulates tracheal cartilage formation. Here we show a core regulatory network underlying murine tracheal chondrogenesis from embryonic day (E) 12.5 to E15.5, by combining volumetric imaging of fluorescence reporters, inhibitor assays, and mathematical modeling. We focused on SRY-box transcription factor 9 (Sox9) and extracellular signal-regulated kinase (ERK) in the tracheal mesenchyme, and observed a synchronous, inverted U-shaped temporal change in both Sox9 expression and ERK activity with a peak at E14.5, whereas the expression level of downstream cartilage matrix genes, such as collagen II alpha 1 (Col2a1) and aggrecan (Agc1), monotonically increased. Inhibitor assays revealed that the ERK signaling pathway functions as an inhibitory regulator of tracheal cartilage differentiation during this period. These results suggest that expression of the cartilage matrix genes is controlled by an incoherent feedforward loop via Sox9 and ERK, which is supported by a mathematical model. Furthermore, the modeling analysis suggests that a Sox9-ERK incoherent feedforward regulation augments the robustness against the variation of upstream factors. The present study provides a better understanding of the regulatory network underlying the tracheal development and will be helpful for efficient induction of tracheal organoids.", "classifications": [], "creators": [ { "creator_type": "author", "first_name": "Takuya", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Michiyuki", "last_name": "Matsuda", "name": null }, { "creator_type": "author", "first_name": "Tsuyoshi", "last_name": "Hirashima", "name": null } ], "identifiers": { "doi": { "normalized": "10.3389/fcell.2020.585640" }, "pmcid": { "normalized": "PMC7642454" }, "pmid": { "normalized": "33195234" } }, "mesh": [], "publication": { "conference_name": null, "date": "2020", "date_precision": "year", "issue": "", "normalized_date": "2020", "pages": "585640", "proceedings_title": null, "publisher": "", "title": "Frontiers in cell and developmental biology", "volume": "8", "year": 2020 }, "ssbd": { "database": [ "ssbd-database-000172" ], "repository": [ "ssbd-repos-000172" ] }, "title": "Incoherent Feedforward Regulation via Sox9 and ERK Underpins Mouse Tracheal Cartilage Development.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Objectives: Mental health problems (MHP) among medical residents are often found in clinical settings and sometimes lead to professional lapses. Evidence suggests that excessive Internet use is associated with MHP. We investigated the MHP of residents (depression, anxiety, and self-esteem) and their association with Internet use using a longitudinal design. Methods: Participants were 208 residents. The General Health Questionnaire (GHQ), Patient Health Questionnaire (PHQ), and the Rosenberg Self-Esteem Scale (RSES) were used to assess anxiety, depression, and self-esteem. The Generalized Problematic Internet Use Scale 2 (GPIUS2) was used to measure Internet use. Data were obtained twice, at baseline and 3 months later when the risk of MHP in residency is highest. Results: Residents with MHP (N = 36) had higher GHQ scores than those without MHP (N = 172) at follow-up. Residents with MHP had more depression and less self-esteem than those without MHP at baseline and follow-up. GPIUS2 total scores, and scores on the subscale preference for online social communication, were higher in residents with MHP. Preference for online social communication at follow-up was positively correlated with depression at baseline and follow-up, and negatively correlated with self-esteem at follow-up. Conclusions: Depression and self-esteem may predict Internet use when the risk of MHP is greatest for residents, indicating potential risks of excessive Internet use or Internet use as a compensatory coping behavior. Together with depression and self-esteem assessment, Internet use may be a useful index of resident mental health.", "classifications": [ { "id": "Fujiwara", "label": "Group Fujiwara", "parent": "Fujiwara", "type": "group" }, { "id": "Fujiwara", "label": "Team Fujiwara", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Tsukasa", "last_name": "Ueno", "name": null }, { "creator_type": "author", "first_name": "Kazushi", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Toshiya", "last_name": "Murai", "name": null }, { "creator_type": "author", "first_name": "Hironobu", "last_name": "Fujiwara", "name": null } ], "identifiers": { "doi": { "normalized": "10.3389/fpubh.2020.587390" }, "pmcid": { "normalized": "PMC7641600" }, "pmid": { "normalized": "33194994" } }, "mesh": [ { "descriptor": "Behavior, Addictive", "descriptor_ui": "D016739", "major_topic": true }, { "descriptor": "Depression", "descriptor_ui": "D003863", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Internet Use", "descriptor_ui": "D000084362", "major_topic": false }, { "descriptor": "Internship and Residency", "descriptor_ui": "D007396", "major_topic": true }, { "descriptor": "Mental Health", "descriptor_ui": "D008603", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020", "date_precision": "year", "issue": "", "normalized_date": "2020", "pages": "587390", "proceedings_title": null, "publisher": "", "title": "Frontiers in public health", "volume": "8", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Mental Health Problems and Their Association With Internet Use in Medical Residents.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Immunosuppressive therapy (IST) is the first-line treatment for young patients with severe aplastic anemia (AA) when a human leucocyte antigen (HLA)-matched related donor (MRD) is unavailable. Fulminant AA (FAA) is defined as AA with a complete absence of neutrophils at presentation and no response to granulocyte-colony stimulating factor (G-CSF) treatment. Here we report a 38-year-old male FAA patient who underwent allogeneic stem cell transplantation from an HLA haplotype-mismatched donor as first-line treatment. The patient had no remarkable disease history and was referred to our hospital because of a peritonsillar abscess and severe pancytopenia. Bone marrow biopsy revealed marked hypocellularity without dysplasia. His neutrophil count remained 0.0x10(9)/l following G-CSF administration, and he was diagnosed with FAA. His siblings were not MRDs, but his sister had haploidentical HLAs. After administering a conditioning regimen, the patient received a transplant of peripheral blood stem cells donated by his sister. Neutrophil engraftment was observed on post-transplant day 16, and he experienced acute graft-versus-host disease (grade I, skin stage 1), but no other complications were observed. Hematopoietic stem cell transplantation from an HLA haplotype-mismatched related donor may be a viable option for first-line treatment of FAA when an MRD is unavailable.", "classifications": [ { "id": "Nishikii", "label": "Group Nishikii", "parent": "Shintaku", "type": "group" }, { "id": "Shintaku", "label": "Team Shintaku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Kenichi", "last_name": "Makishima", "name": null }, { "creator_type": "author", "first_name": "Naoshi", "last_name": "Obara", "name": null }, { "creator_type": "author", "first_name": "Tatsuhiro", "last_name": "Sakamoto", "name": null }, { "creator_type": "author", "first_name": "Takayasu", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Manabu", "last_name": "Kusakabe", "name": null }, { "creator_type": "author", "first_name": "Hidekazu", "last_name": "Nishikii", "name": null }, { "creator_type": "author", "first_name": "Naoki", "last_name": "Kurita", "name": null }, { "creator_type": "author", "first_name": "Yasuhisa", "last_name": "Yokoyama", "name": null }, { "creator_type": "author", "first_name": "Mamiko", "last_name": "Sakata-Yanagimoto", "name": null }, { "creator_type": "author", "first_name": "Yuichi", "last_name": "Hasegawa", "name": null }, { "creator_type": "author", "first_name": "Shigeru", "last_name": "Chiba", "name": null } ], "identifiers": { "doi": { "normalized": "10.11406/rinketsu.61.1464" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "33162441" } }, "mesh": [ { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Anemia, Aplastic", "descriptor_ui": "D000741", "major_topic": true }, { "descriptor": "Graft vs Host Disease", "descriptor_ui": "D006086", "major_topic": true }, { "descriptor": "Granulocyte Colony-Stimulating Factor", "descriptor_ui": "D016179", "major_topic": false }, { "descriptor": "Hematopoietic Stem Cell Transplantation", "descriptor_ui": "D018380", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Transplantation Conditioning", "descriptor_ui": "D019172", "major_topic": false }, { "descriptor": "Transplantation, Haploidentical", "descriptor_ui": "D000075442", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020", "date_precision": "year", "issue": "10", "normalized_date": "2020", "pages": "1464-1468", "proceedings_title": null, "publisher": "", "title": "[Rinsho ketsueki] The Japanese journal of clinical hematology", "volume": "61", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "[Haploidentical transplantation from a related donor as first-line treatment for fulminant aplastic anemia].", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The zygote is the first cell of a multicellular organism. In most angiosperms, the zygote divides asymmetrically to produce an embryo-precursor apical cell and a supporting basal cell. Zygotic division should properly segregate symbiotic organelles, because they cannot be synthesized de novo. In this study, we revealed the real-time dynamics of the principle source of ATP biogenesis, mitochondria, in Arabidopsis thaliana zygotes using live-cell observations and image quantifications. In the zygote, the mitochondria formed the extended structure associated with the longitudinal array of actin filaments (F-actins) and were polarly distributed along the apical-basal axis. The mitochondria were then temporally fragmented during zygotic division, and the resulting apical cells inherited mitochondria at higher concentration compared to the basal cells. Further observation of postembryonic organs showed that these mitochondrial behaviours are characteristic of the zygote. Overall, our results showed that the zygote has spatiotemporal regulation that unequally distributes the mitochondria.", "classifications": [ { "id": "Higaki", "label": "Group Higaki", "parent": "Ueda", "type": "group" }, { "id": "Ueda", "label": "Group Ueda", "parent": "Ueda", "type": "group" }, { "id": "Ueda", "label": "Team Ueda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yusuke", "last_name": "Kimata", "name": null }, { "creator_type": "author", "first_name": "Takumi", "last_name": "Higaki", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Kurihara", "name": null }, { "creator_type": "author", "first_name": "Naoe", "last_name": "Ando", "name": null }, { "creator_type": "author", "first_name": "Hikari", "last_name": "Matsumoto", "name": null }, { "creator_type": "author", "first_name": "Tetsuya", "last_name": "Higashiyama", "name": null }, { "creator_type": "author", "first_name": "Minako", "last_name": "Ueda", "name": null } ], "identifiers": { "doi": { "normalized": "10.1017/qpb.2020.4" }, "pmcid": { "normalized": "PMC10095797" }, "pmid": { "normalized": "37077329" } }, "mesh": [], "publication": { "conference_name": null, "date": "2020", "date_precision": "year", "issue": "", "normalized_date": "2020", "pages": "e3", "proceedings_title": null, "publisher": "", "title": "Quantitative plant biology", "volume": "1", "year": 2020 }, "ssbd": { "database": [ "ssbd-database-000324" ], "repository": [ "ssbd-repos-000324" ] }, "title": "Mitochondrial dynamics and segregation during the asymmetric division of Arabidopsis zygotes.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "We have developed a catalytic aerobic oxidative dimerization reaction of benzofuranones using a Pd(II)-micro-hydroxo complex. Radical-radical cross-coupling of the resulting dimers with azo compounds enabled the one-pot synthesis of structurally congested benzofuranones having two distinct vicinal all-carbon quaternary centers.", "classifications": [ { "id": "Sodeoka", "label": "Group Sodeoka", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Rikako", "last_name": "Ohnishi", "name": null }, { "creator_type": "author", "first_name": "Masumi", "last_name": "Sugawara", "name": null }, { "creator_type": "author", "first_name": "Tetsuya", "last_name": "Ezawa", "name": null }, { "creator_type": "author", "first_name": "Yoshihiro", "last_name": "Sohtome", "name": null }, { "creator_type": "author", "first_name": "Mikiko", "last_name": "Sodeoka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1248/cpb.c20-00359" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "32879230" } }, "mesh": [ { "descriptor": "Azo Compounds", "descriptor_ui": "D001391", "major_topic": false }, { "descriptor": "Benzofurans", "descriptor_ui": "D001572", "major_topic": false }, { "descriptor": "Catalysis", "descriptor_ui": "D002384", "major_topic": false }, { "descriptor": "Molecular Structure", "descriptor_ui": "D015394", "major_topic": false }, { "descriptor": "Oxidation-Reduction", "descriptor_ui": "D010084", "major_topic": false }, { "descriptor": "Palladium", "descriptor_ui": "D010165", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020", "date_precision": "year", "issue": "9", "normalized_date": "2020", "pages": "895-898", "proceedings_title": null, "publisher": "", "title": "Chemical & pharmaceutical bulletin", "volume": "68", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Formal Aerobic Oxidative Cross-Coupling of Benzofuranones with Azo Compounds Using Pd-mu-hydroxo Complex.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Niemann-Pick disease type C is a rare, fatal neurodegenerative disorder characterized by massive intracellular accumulation of cholesterol. In most cases, loss-of-function mutations in the NPC1 gene that encodes lysosomal cholesterol transporter NPC1 are responsible for the disease, and more than half of the mutations are considered to interfere with the biogenesis or folding of the protein. We previously identified a series of oxysterol derivatives and phenanthridine-6-one derivatives as pharmacological chaperones, i.e., small molecules that can rescue folding-defective phenotypes of mutated NPC1, opening up an avenue to develop chaperone therapy for Niemann-Pick disease type C. Here, we present an improved image-based screen for NPC1 chaperones and we describe its application for drug-repurposing screening. We identified some azole antifungals, including itraconazole and posaconazole, and a kinase inhibitor, lapatinib, as probable pharmacological chaperones. A photo-crosslinking study confirmed direct binding of itraconazole to a representative folding-defective mutant protein, NPC1-I1061T. Competitive photo-crosslinking experiments suggested that oxysterol-based chaperones and itraconazole share the same or adjacent binding site(s), and the sensitivity of the crosslinking to P691S mutation in the sterol-sensing domain supports the hypothesis that their binding sites are located near this domain. Although the azoles were less effective in reducing cholesterol accumulation than the oxysterol-derived chaperones or an HDAC inhibitor, LBH-589, our findings should offer new starting points for medicinal chemistry efforts to develop better pharmacological chaperones for NPC1.", "classifications": [ { "id": "Sodeoka", "label": "Group Sodeoka", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Ryuta", "last_name": "Shioi", "name": null }, { "creator_type": "author", "first_name": "Fumika", "last_name": "Karaki", "name": null }, { "creator_type": "author", "first_name": "Hiromasa", "last_name": "Yoshioka", "name": null }, { "creator_type": "author", "first_name": "Tomomi", "last_name": "Noguchi-Yachide", "name": null }, { "creator_type": "author", "first_name": "Minoru", "last_name": "Ishikawa", "name": null }, { "creator_type": "author", "first_name": "Kosuke", "last_name": "Dodo", "name": null }, { "creator_type": "author", "first_name": "Yuichi", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Mikiko", "last_name": "Sodeoka", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Ohgane", "name": null } ], "identifiers": { "doi": { "normalized": "10.1371/journal.pone.0243746" }, "pmcid": { "normalized": "PMC7735562" }, "pmid": { "normalized": "33315900" } }, "mesh": [ { "descriptor": "Drug Discovery", "descriptor_ui": "D055808", "major_topic": false }, { "descriptor": "Drug Repositioning", "descriptor_ui": "D058492", "major_topic": false }, { "descriptor": "HEK293 Cells", "descriptor_ui": "D057809", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Intracellular Signaling Peptides and Proteins", "descriptor_ui": "D047908", "major_topic": false }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": false }, { "descriptor": "Niemann-Pick C1 Protein", "descriptor_ui": "D000077296", "major_topic": false }, { "descriptor": "Niemann-Pick Disease, Type C", "descriptor_ui": "D052556", "major_topic": false }, { "descriptor": "Protein Folding", "descriptor_ui": "D017510", "major_topic": false }, { "descriptor": "Small Molecule Libraries", "descriptor_ui": "D054852", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020", "date_precision": "year", "issue": "12", "normalized_date": "2020", "pages": "e0243746", "proceedings_title": null, "publisher": "", "title": "PloS one", "volume": "15", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Image-based screen capturing misfolding status of Niemann-Pick type C1 identifies potential candidates for chaperone drugs.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Extracellular vesicles (EVs) in the tumor microenvironment facilitate intercellular communication. Cancer cell-derived EVs act as an immunosuppressor by transporting cargos and presenting transmembrane proteins. By contrast, CD8+ cytotoxic T-lymphocytes (CTLs) exert anti-cancer cytotoxicity via the pore-forming protein perforin. Here, we hypothesize that although EVs are destroyed by perforin, cancer cell-derived EVs might possess mechanisms that enable them to avoid this destruction. We used a breast cancer cell line, MDA-MB-231-luc-D3H2LN (D3H2LN), to generate EVs. Destruction of the EVs by perforin was demonstrated visually using atomic force microscopy. To investigate immunosuppressive metabolites within cancer cell-derived EVs, we performed metabolomic profiling of EVs from D3H2LN cells cultured for 48 h with or without IFN-gamma, which induces metabolic changes in the cells. We found that both types of EV from IFN-gamma treated D3H2LN cells and non-treated D3H2LN cells contained adenosine, which has immunosuppressive effects. When we exposed cancer cell-derived EVs to CTLs, perforin secretion by CTLs fell significantly. In addition, the decreases in perforin secretion were ameliorated by treatment with adenosine deaminase, which degrades extracellular adenosine. Taken together, these results suggest that after perforin secreted by CTLs disrupts the membrane of EVs, adenosine released from the EVs acts as an immunosuppressive metabolite by binding to the adenosine receptor on the CTL membrane. This mechanism provides a novel survival strategy using cancer cell-derived EVs.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Hiroko", "last_name": "Tadokoro", "name": null }, { "creator_type": "author", "first_name": "Akiyoshi", "last_name": "Hirayama", "name": null }, { "creator_type": "author", "first_name": "Ryuhei", "last_name": "Kudo", "name": null }, { "creator_type": "author", "first_name": "Masako", "last_name": "Hasebe", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Yoshioka", "name": null }, { "creator_type": "author", "first_name": "Juntaro", "last_name": "Matsuzaki", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Sugimoto", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Takahiro", "last_name": "Ochiya", "name": null } ], "identifiers": { "doi": { "normalized": "10.1371/journal.pone.0231430" }, "pmcid": { "normalized": "PMC7147783" }, "pmid": { "normalized": "32275689" } }, "mesh": [ { "descriptor": "Adenosine", "descriptor_ui": "D000241", "major_topic": false }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Extracellular Vesicles", "descriptor_ui": "D000067128", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Interferon-gamma", "descriptor_ui": "D007371", "major_topic": false }, { "descriptor": "Perforin", "descriptor_ui": "D054353", "major_topic": false }, { "descriptor": "T-Lymphocytes, Cytotoxic", "descriptor_ui": "D013602", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020", "date_precision": "year", "issue": "4", "normalized_date": "2020", "pages": "e0231430", "proceedings_title": null, "publisher": "", "title": "PloS one", "volume": "15", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Adenosine leakage from perforin-burst extracellular vesicles inhibits perforin secretion by cytotoxic T-lymphocytes.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "", "classifications": [ { "id": "Morishita", "label": "Group Morishita", "parent": "Morishita", "type": "group" }, { "id": "Morishita", "label": "Team Morishita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yoshihiro", "last_name": "Morishita", "name": null }, { "creator_type": "author", "first_name": "Tomoya", "last_name": "Kitajima", "name": null }, { "creator_type": "author", "first_name": "Shunsuke", "last_name": "Tagami", "name": null }, { "creator_type": "author", "first_name": "Minoru", "last_name": "Takasato", "name": null }, { "creator_type": "author", "first_name": "Yo", "last_name": "Tanaka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/dgd.12658" }, "pmcid": { "normalized": null }, "pmid": { "normalized": null } }, "mesh": [], "publication": { "conference_name": null, "date": "2020", "date_precision": "year", "issue": "3", "normalized_date": "2020", "pages": "149-149", "proceedings_title": null, "publisher": "", "title": "Development, Growth & Differentiation", "volume": "62", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Control and design of biosystems", "url": "https://onlinelibrary.wiley.com/doi/abs/10.1111/dgd.12658", "zotero": { "item_type": "journalArticle" } }, { "abstract": "", "classifications": [ { "id": "Higaki", "label": "Group Higaki", "parent": "Ueda", "type": "group" }, { "id": "Ueda", "label": "Team Ueda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Akiko", "last_name": "Nakamasu", "name": null }, { "creator_type": "author", "first_name": "Takumi", "last_name": "Higaki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/s10265-020-01178-z" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "32212041" } }, "mesh": [], "publication": { "conference_name": null, "date": "2020", "date_precision": "year", "issue": "3", "normalized_date": "2020", "pages": "443", "proceedings_title": null, "publisher": "", "title": "Journal of Plant Research", "volume": "133", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Correction to: Theoretical models for branch formation in plants.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BD5 is a new binary data format based on HDF5 (hierarchical data format version 5). It can be used for representing quantitative biological dynamics data obtained from bioimage informatics techniques and mechanobiological simulations. Biological Dynamics Markup Language (BDML) is an XML (Extensible Markup Language)-based open format that is also used to represent such data; however, it becomes difficult to access quantitative data in BDML files when the file size is large because parsing XML-based files requires large computational resources to first read the whole file sequentially into computer memory. BD5 enables fast random (i.e., direct) access to quantitative data on disk without parsing the entire file. Therefore, it allows practical reuse of data for understanding biological mechanisms underlying the dynamics.", "classifications": [ { "id": "Onami", "label": "Group Onami", "parent": "Fujiwara", "type": "group" }, { "id": "Fujiwara", "label": "Team Fujiwara", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Koji", "last_name": "Kyoda", "name": null }, { "creator_type": "author", "first_name": "Kenneth H. L.", "last_name": "Ho", "name": null }, { "creator_type": "author", "first_name": "Yukako", "last_name": "Tohsato", "name": null }, { "creator_type": "author", "first_name": "Hiroya", "last_name": "Itoga", "name": null }, { "creator_type": "author", "first_name": "Shuichi", "last_name": "Onami", "name": null } ], "identifiers": { "doi": { "normalized": "10.1371/journal.pone.0237468" }, "pmcid": { "normalized": "PMC7423140" }, "pmid": { "normalized": "32785254" } }, "mesh": [ { "descriptor": "Computational Biology", "descriptor_ui": "D019295", "major_topic": false }, { "descriptor": "Databases, Factual", "descriptor_ui": "D016208", "major_topic": false }, { "descriptor": "Programming Languages", "descriptor_ui": "D011381", "major_topic": true }, { "descriptor": "Software", "descriptor_ui": "D012984", "major_topic": false }, { "descriptor": "Software Design", "descriptor_ui": "D012985", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020", "date_precision": "year", "issue": "8", "normalized_date": "2020", "pages": "e0237468", "proceedings_title": null, "publisher": "", "title": "PloS one", "volume": "15", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "BD5: An open HDF5-based data format to represent quantitative biological dynamics data.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Background: Streptozocin (STZ) is used for treating both pancreatic (PanNET) and gastrointestinal (GI-NET) neuroendocrine tumors but its therapeutic efficacy is relatively low in GI-NETs. Therefore, it has become pivotal to select GI-NET patients who could benefit from STZ treatment. STZ is transported via the glucose transporter 2 (GLUT2) into the cells and the loss of O6-methylguanine DNA methyltransferase (MGMT) also increases its therapeutic efficacy. Therefore, GLUT2 high and MGMT low status could be the surrogate markers of STZ. Methods: In this study, we examined the MGMT and GLUT2 status in gastrointestinal neuroendocrine neoplasm (NEN). We studied 84 NEN cases: 33 foregut and 37 hindgut GI-NETs and 14 gastrointestinal neuroendocrine carcinomas (GI-NECs). Results: In GI-NETs, MGMT scores of ≥2 and ≥ 3 were 77% (54/70) and 56% (39/70), respectively, and GLUT2 scores of ≥4 and ≥ 6 were 30% (21/70) and 4.3% (3/70), respectively. Methylation-specific polymerase chain reaction revealed that MGMT promoter methylation was detected only in 2/14 GI-NECs but none of the included GI-NETs. GLUT2 (GLUT2 score) and MGMT immunoreactivity (MGMT and H-scores) were both significantly correlated with Ki-67 labeling index (GLUT2 score: P = 0.0045, ρ = − 0.4570; MGMT score: P = 0.0064, ρ = − 0.4399; H-score: P = 0.0110, ρ = − 0.4135) and MGMT immunoreactivity were significantly correlated with GLUT2 immunoreactivity (MGMT score: P = 0.0198; H-score, P = 0.0004, ρ = 0.5483) in hindgut NETs, but not in foregut NETs. However, discrepancies from the above correlation between GLUT2 and MGMT immunoreactivity were detected in several GI-NET cases which could be potential candidates for STZ therapy. Conclusion: The evaluation of MGMT and GLUT2 status could provide an important information in planning STZ therapy in GI-NET patients. Supplementary Information: The online version contains supplementary material available at 10.1186/s12885-020-07579-6.", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Hirofumi", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Yuto", "last_name": "Yamazaki", "name": null }, { "creator_type": "author", "first_name": "Fumiyoshi", "last_name": "Fujishima", "name": null }, { "creator_type": "author", "first_name": "Komoto", "last_name": "Izumi", "name": null }, { "creator_type": "author", "first_name": "Masayuki", "last_name": "Imamura", "name": null }, { "creator_type": "author", "first_name": "Susumu", "last_name": "Hijioka", "name": null }, { "creator_type": "author", "first_name": "Kazuhiro", "last_name": "Toriyama", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Kudo", "name": null }, { "creator_type": "author", "first_name": "Fuyuhiko", "last_name": "Motoi", "name": null }, { "creator_type": "author", "first_name": "Michiaki", "last_name": "Unno", "name": null }, { "creator_type": "author", "first_name": "Hironobu", "last_name": "Sasano", "name": null } ], "identifiers": { "doi": { "normalized": "10.1186/s12885-020-07579-6" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "33287738" } }, "mesh": [ { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Aged, 80 and over", "descriptor_ui": "D000369", "major_topic": false }, { "descriptor": "DNA Modification Methylases", "descriptor_ui": "D015254", "major_topic": false }, { "descriptor": "DNA Repair Enzymes", "descriptor_ui": "D045643", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Gastrointestinal Neoplasms", "descriptor_ui": "D005770", "major_topic": false }, { "descriptor": "Glucose Transporter Type 2", "descriptor_ui": "D051273", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Immunohistochemistry", "descriptor_ui": "D007150", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Methylation", "descriptor_ui": "D008745", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Neuroendocrine Tumors", "descriptor_ui": "D018358", "major_topic": false }, { "descriptor": "Streptozocin", "descriptor_ui": "D013311", "major_topic": false }, { "descriptor": "Tumor Suppressor Proteins", "descriptor_ui": "D025521", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020", "date_precision": "year", "issue": "", "normalized_date": "2020", "pages": "", "proceedings_title": null, "publisher": "", "title": "BMC Cancer", "volume": "20", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "O6-methylguanine DNA methyltransferase and glucose transporter 2 in foregut and hindgut gastrointestinal neuroendocrine neoplasms.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Activity-dependent remodeling of excitatory connections underpins memory formation in the brain. Serotonin receptors are known to contribute to such remodeling, yet the underlying molecular machinery remains poorly understood. Here, we employ high-resolution time-lapse FRET imaging in neuroblastoma cells and neuronal dendrites to establish that activation of serotonin receptor 5-HT4 (5-HT4R) rapidly triggers spatially-restricted RhoA activity and G13-mediated phosphorylation of cofilin, thus locally boosting the filamentous actin fraction. In neuroblastoma cells, this leads to cell rounding and neurite retraction. In hippocampal neurons in situ, 5-HT4R-mediated RhoA activation triggers maturation of dendritic spines. This is paralleled by RhoA-dependent, transient alterations in cell excitability, as reflected by increased spontaneous synaptic activity, apparent shunting of evoked synaptic responses, and enhanced long-term potentiation of excitatory transmission. The 5-HT4R/G13/RhoA signaling thus emerges as a previously unrecognized molecular pathway underpinning use-dependent functional remodeling of excitatory synaptic connections.", "classifications": [], "creators": [ { "creator_type": "author", "first_name": "Yvonne", "last_name": "Schill", "name": null }, { "creator_type": "author", "first_name": "Monika", "last_name": "Bijata", "name": null }, { "creator_type": "author", "first_name": "Olga", "last_name": "Kopach", "name": null }, { "creator_type": "author", "first_name": "Volodymyr", "last_name": "Cherkas", "name": null }, { "creator_type": "author", "first_name": "Dalia", "last_name": "Abdel-Galil", "name": null }, { "creator_type": "author", "first_name": "Katrin", "last_name": "Böhm", "name": null }, { "creator_type": "author", "first_name": "Markus H.", "last_name": "Schwab", "name": null }, { "creator_type": "author", "first_name": "Michiyuki", "last_name": "Matsuda", "name": null }, { "creator_type": "author", "first_name": "Valerie", "last_name": "Compan", "name": null }, { "creator_type": "author", "first_name": "Subhadip", "last_name": "Basu", "name": null }, { "creator_type": "author", "first_name": "Krystian", "last_name": "Bijata", "name": null }, { "creator_type": "author", "first_name": "Jakub", "last_name": "Wlodarczyk", "name": null }, { "creator_type": "author", "first_name": "Lucie", "last_name": "Bard", "name": null }, { "creator_type": "author", "first_name": "Nicholas", "last_name": "Cole", "name": null }, { "creator_type": "author", "first_name": "Alexander", "last_name": "Dityatev", "name": null }, { "creator_type": "author", "first_name": "Andre", "last_name": "Zeug", "name": null }, { "creator_type": "author", "first_name": "Dmitri A.", "last_name": "Rusakov", "name": null }, { "creator_type": "author", "first_name": "Evgeni", "last_name": "Ponimaskin", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s42003-020-0791-x" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "32060357" } }, "mesh": [ { "descriptor": "Actin Cytoskeleton", "descriptor_ui": "D008841", "major_topic": false }, { "descriptor": "Actins", "descriptor_ui": "D000199", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Animals, Newborn", "descriptor_ui": "D000831", "major_topic": false }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Dendritic Spines", "descriptor_ui": "D049229", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Long-Term Potentiation", "descriptor_ui": "D017774", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Rats, Sprague-Dawley", "descriptor_ui": "D017207", "major_topic": false }, { "descriptor": "Receptors, Serotonin, 5-HT4", "descriptor_ui": "D044422", "major_topic": false }, { "descriptor": "rhoA GTP-Binding Protein", "descriptor_ui": "D020742", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Synapses", "descriptor_ui": "D013569", "major_topic": false }, { "descriptor": "Synaptic Transmission", "descriptor_ui": "D009435", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020", "date_precision": "year", "issue": "", "normalized_date": "2020", "pages": "", "proceedings_title": null, "publisher": "", "title": "Communications Biology", "volume": "3", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Serotonin 5-HT4 receptor boosts functional maturation of dendritic spines via RhoA-dependent control of F-actin.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The three-dimensional (3D) genome organization and its role in biological activities have been investigated for over a decade in the field of cell biology. Recent studies using live-imaging and polymer simulation have suggested that the higher-order chromatin structures are dynamic; the stochastic fluctuations of nucleosomes and genomic loci cannot be captured by bulk-based chromosome conformation capture techniques (Hi-C). In this review, we focus on the physical nature of the 3D genome architecture. We first describe how to decode bulk Hi-C data with polymer modeling. We then introduce our recently developed PHi-C method, a computational tool for modeling the fluctuations of the 3D genome organization in the presence of stochastic thermal noise. We also present another new method that analyzes the dynamic rheology property (represented as microrheology spectra) as a measure of the flexibility and rigidity of genomic regions over time. By applying these methods to real Hi-C data, we highlighted a temporal hierarchy embedded in the 3D genome organization; chromatin interaction boundaries are more rigid than the boundary interior, while functional domains emerge as dynamic fluctuations within a particular time interval. Our methods may bridge the gap between live-cell imaging and Hi-C data and elucidate the nature of the dynamic 3D genome organization.", "classifications": [ { "id": "Onami", "label": "Group Onami", "parent": "Fujiwara", "type": "group" }, { "id": "Fujiwara", "label": "Team Fujiwara", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Soya", "last_name": "Shinkai", "name": null }, { "creator_type": "author", "first_name": "Shuichi", "last_name": "Onami", "name": null }, { "creator_type": "author", "first_name": "Ryuichiro", "last_name": "Nakato", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.csbj.2020.08.014" }, "pmcid": { "normalized": "PMC7484532" }, "pmid": { "normalized": "32952939" } }, "mesh": [], "publication": { "conference_name": null, "date": "2020", "date_precision": "year", "issue": "", "normalized_date": "2020", "pages": "2259-2269", "proceedings_title": null, "publisher": "", "title": "Computational and structural biotechnology journal", "volume": "18", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Toward understanding the dynamic state of 3D genome.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The LUBAC ubiquitin ligase complex, composed of the HOIP, HOIL-1L, and SHARPIN subunits, stimulates the canonical nuclear factor-kappaB (NF-kappaB) activation pathways through its Met1-linked linear ubiquitination activity. Here we performed cellular and mathematical modeling analyses of the LUBAC involvement in the T cell receptor (TCR)-mediated NF-kappaB activation pathway, using the Jurkat human T cell line. LUBAC is indispensable for TCR-induced NF-kappaB and T cell activation, and transiently associates with and linearly ubiquitinates the CARMA1-BCL10-MALT1 (CBM) complex, through the catalytic HOIP subunit. In contrast, the linear ubiquitination of NEMO, a substrate of the TNF-alpha-induced canonical NF-kappaB activation pathway, was limited during the TCR pathway. Among deubiquitinases, OTULIN, but not CYLD, plays a major role in downregulating LUBAC-mediated TCR signaling. Mathematical modeling indicated that linear ubiquitination of the CBM complex accelerates the activation of IkappaB kinase (IKK), as compared with the activity induced by linear ubiquitination of NEMO alone. Moreover, simulations of the sequential linear ubiquitination of the CBM complex suggested that the allosteric regulation of linear (de)ubiquitination of CBM subunits is controlled by the ubiquitin-linkage lengths. These results indicated that, unlike the TNF-alpha-induced NF-kappaB activation pathway, the TCR-mediated NF-kappaB activation in T lymphocytes has a characteristic mechanism to induce LUBAC-mediated NF-kappaB activation.", "classifications": [ { "id": "Suzuki", "label": "Group Suzuki", "parent": "Takekawa", "type": "group" }, { "id": "Takekawa", "label": "Team Takekawa", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Daisuke", "last_name": "Oikawa", "name": null }, { "creator_type": "author", "first_name": "Naoya", "last_name": "Hatanaka", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Fuminori", "last_name": "Tokunaga", "name": null } ], "identifiers": { "doi": { "normalized": "10.3389/fimmu.2020.601926" }, "pmcid": { "normalized": "PMC7732508" }, "pmid": { "normalized": "33329596" } }, "mesh": [ { "descriptor": "Antibodies", "descriptor_ui": "D000906", "major_topic": false }, { "descriptor": "B-Cell CLL-Lymphoma 10 Protein", "descriptor_ui": "D000074018", "major_topic": false }, { "descriptor": "CARD Signaling Adaptor Proteins", "descriptor_ui": "D053468", "major_topic": false }, { "descriptor": "Computer Simulation", "descriptor_ui": "D003198", "major_topic": false }, { "descriptor": "Deubiquitinating Enzyme CYLD", "descriptor_ui": "D000074749", "major_topic": false }, { "descriptor": "Endopeptidases", "descriptor_ui": "D010450", "major_topic": false }, { "descriptor": "Guanylate Cyclase", "descriptor_ui": "D006162", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Jurkat Cells", "descriptor_ui": "D019169", "major_topic": false }, { "descriptor": "Lymphocyte Activation", "descriptor_ui": "D008213", "major_topic": true }, { "descriptor": "Models, Immunological", "descriptor_ui": "D018448", "major_topic": true }, { "descriptor": "Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Protein", "descriptor_ui": "D000074884", "major_topic": false }, { "descriptor": "Multienzyme Complexes", "descriptor_ui": "D009097", "major_topic": false }, { "descriptor": "NF-kappa B", "descriptor_ui": "D016328", "major_topic": false }, { "descriptor": "Receptors, Antigen, T-Cell", "descriptor_ui": "D011948", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "T-Lymphocytes", "descriptor_ui": "D013601", "major_topic": false }, { "descriptor": "Transcription Factors", "descriptor_ui": "D014157", "major_topic": false }, { "descriptor": "Ubiquitin-Protein Ligases", "descriptor_ui": "D044767", "major_topic": false }, { "descriptor": "Ubiquitination", "descriptor_ui": "D054875", "major_topic": false }, { "descriptor": "Ubiquitins", "descriptor_ui": "D014452", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020", "date_precision": "year", "issue": "", "normalized_date": "2020", "pages": "601926", "proceedings_title": null, "publisher": "", "title": "Frontiers in immunology", "volume": "11", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Cellular and Mathematical Analyses of LUBAC Involvement in T Cell Receptor-Mediated NF-kappaB Activation Pathway.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Space travel has advanced significantly over the last six decades with astronauts spending up to 6 months at the International Space Station. Nonetheless, the living environment while in outer space is extremely challenging to astronauts. In particular, exposure to space radiation represents a serious potential long-term threat to the health of astronauts because the amount of radiation exposure accumulates during their time in space. Therefore, health risks associated with exposure to space radiation are an important topic in space travel, and characterizing space radiation in detail is essential for improving the safety of space missions. In the first part of this review, we provide an overview of the space radiation environment and briefly present current and future endeavors that monitor different space radiation environments. We then present research evaluating adverse biological effects caused by exposure to various space radiation environments and how these can be reduced. We especially consider the deleterious effects on cellular DNA and how cells activate DNA repair mechanisms. The latest technologies being developed, e.g., a fluorescent ubiquitination-based cell cycle indicator, to measure real-time cell cycle progression and DNA damage caused by exposure to ultraviolet radiation are presented. Progress in examining the combined effects of microgravity and radiation to animals and plants are summarized, and our current understanding of the relationship between psychological stress and radiation is presented. Finally, we provide details about protective agents and the study of organisms that are highly resistant to radiation and how their biological mechanisms may aid developing novel technologies that alleviate biological damage caused by radiation. Future research that furthers our understanding of the effects of space radiation on human health will facilitate risk-mitigating strategies to enable long-term space and planetary exploration.", "classifications": [ { "id": "Sawano", "label": "Group Sawano", "parent": "Shintaku", "type": "group" }, { "id": "Shintaku", "label": "Team Shintaku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Satoshi", "last_name": "Furukawa", "name": null }, { "creator_type": "author", "first_name": "Aiko", "last_name": "Nagamatsu", "name": null }, { "creator_type": "author", "first_name": "Mitsuru", "last_name": "Nenoi", "name": null }, { "creator_type": "author", "first_name": "Akira", "last_name": "Fujimori", "name": null }, { "creator_type": "author", "first_name": "Shizuko", "last_name": "Kakinuma", "name": null }, { "creator_type": "author", "first_name": "Takanori", "last_name": "Katsube", "name": null }, { "creator_type": "author", "first_name": "Bing", "last_name": "Wang", "name": null }, { "creator_type": "author", "first_name": "Chizuru", "last_name": "Tsuruoka", "name": null }, { "creator_type": "author", "first_name": "Toshiyuki", "last_name": "Shirai", "name": null }, { "creator_type": "author", "first_name": "Asako J.", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Asako", "last_name": "Sakaue-Sawano", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Miyawaki", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Harada", "name": null }, { "creator_type": "author", "first_name": "Minoru", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Junya", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Takekazu", "last_name": "Kunieda", "name": null }, { "creator_type": "author", "first_name": "Tomoo", "last_name": "Funayama", "name": null }, { "creator_type": "author", "first_name": "Michiyo", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Tatsuo", "last_name": "Miyamoto", "name": null }, { "creator_type": "author", "first_name": "Jun", "last_name": "Hidema", "name": null }, { "creator_type": "author", "first_name": "Yukari", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Akihisa", "last_name": "Takahashi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1155/2020/4703286" }, "pmcid": { "normalized": "PMC7168699" }, "pmid": { "normalized": "32337251" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Astronauts", "descriptor_ui": "D018480", "major_topic": false }, { "descriptor": "Carcinogenesis", "descriptor_ui": "D063646", "major_topic": false }, { "descriptor": "Central Nervous System", "descriptor_ui": "D002490", "major_topic": false }, { "descriptor": "Chromosome Aberrations", "descriptor_ui": "D002869", "major_topic": false }, { "descriptor": "Cosmic Radiation", "descriptor_ui": "D003359", "major_topic": false }, { "descriptor": "DNA Damage", "descriptor_ui": "D004249", "major_topic": false }, { "descriptor": "DNA Repair", "descriptor_ui": "D004260", "major_topic": false }, { "descriptor": "Extraterrestrial Environment", "descriptor_ui": "D005118", "major_topic": false }, { "descriptor": "Genomic Instability", "descriptor_ui": "D042822", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Micronuclei, Chromosome-Defective", "descriptor_ui": "D048629", "major_topic": false }, { "descriptor": "Protective Agents", "descriptor_ui": "D020011", "major_topic": false }, { "descriptor": "Radiation Dosage", "descriptor_ui": "D011829", "major_topic": false }, { "descriptor": "Radiation Exposure", "descriptor_ui": "D000069079", "major_topic": false }, { "descriptor": "Space Flight", "descriptor_ui": "D013026", "major_topic": true }, { "descriptor": "Stress, Psychological", "descriptor_ui": "D013315", "major_topic": false }, { "descriptor": "Ultraviolet Rays", "descriptor_ui": "D014466", "major_topic": true }, { "descriptor": "Weightlessness", "descriptor_ui": "D014893", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020", "date_precision": "year", "issue": "", "normalized_date": "2020", "pages": "4703286", "proceedings_title": null, "publisher": "", "title": "BioMed research international", "volume": "2020", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Space Radiation Biology for \"Living in Space\".", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "OBJECTIVE: The aim of this supplemental study of a sentinel node (SN) biopsy (SNB) trial for oral squamous cell carcinoma (OSCC) was to assess the effectiveness in identifying micrometastasis and determining whether elective neck dissection (END) is necessary.MATERIALS AND METHODS: Twenty-three patients with pathologically positive SNs were included. The sizes of the metastatic lesions in positive SNs (SMSNs) were classified and the rates of occult metastasis of non-SNs were compared.RESULTS: The patients were divided according to the SMSN: <0.2 mm (group A, n=3);0.2 mm to <2.0 mm (group B, n=7);and ≥2.0 mm (group C, n=13). The rates of occult metastasis in groups A, B, and C were 0% (0/3), 14% (1/7) and 23% (3/13), respectively.CONCLUSION: Rare cancer cell distribution to nodes other than SNs was observed in the patients with SN metastatic lesions of at least smaller than 0.2 mm in size, suggesting the possibility of defining SN micrometastasis in N0 OSCC.", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Takashi", "last_name": "Matsuzuka", "name": null }, { "creator_type": "author", "first_name": "Hirokazu", "last_name": "Uemura", "name": null }, { "creator_type": "author", "first_name": "Seiichi", "last_name": "Yoshimoto", "name": null }, { "creator_type": "author", "first_name": "Kouki", "last_name": "Miura", "name": null }, { "creator_type": "author", "first_name": "Akihiro", "last_name": "Shiotani", "name": null }, { "creator_type": "author", "first_name": "Masashi", "last_name": "Sugasawa", "name": null }, { "creator_type": "author", "first_name": "Akihiro", "last_name": "Homma", "name": null }, { "creator_type": "author", "first_name": "Junkichi", "last_name": "Yokoyama", "name": null }, { "creator_type": "author", "first_name": "Kiyoaki", "last_name": "Tsukahara", "name": null }, { "creator_type": "author", "first_name": "Tomokazu", "last_name": "Yoshizaki", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null }, { "creator_type": "author", "first_name": "Takehiro", "last_name": "Kobari", "name": null }, { "creator_type": "author", "first_name": "Shigeru", "last_name": "Kosuda", "name": null }, { "creator_type": "author", "first_name": "Shigeyuki", "last_name": "Murono", "name": null }, { "creator_type": "author", "first_name": "Yasuhisa", "last_name": "Hasegawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.5387/fms.2020-17" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "33268599" } }, "mesh": [ { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Aged, 80 and over", "descriptor_ui": "D000369", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Lymphatic Metastasis", "descriptor_ui": "D008207", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Mouth Neoplasms", "descriptor_ui": "D009062", "major_topic": false }, { "descriptor": "Neoplasm Micrometastasis", "descriptor_ui": "D061206", "major_topic": true }, { "descriptor": "Sentinel Lymph Node", "descriptor_ui": "D000071036", "major_topic": false }, { "descriptor": "Squamous Cell Carcinoma of Head and Neck", "descriptor_ui": "D000077195", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020", "date_precision": "year", "issue": "3", "normalized_date": "2020", "pages": "143-147", "proceedings_title": null, "publisher": "", "title": "Fukushima Journal of Medical Science", "volume": "66", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Attempting to define sentinel node micrometastasis in oral squamous cell carcinoma.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "PURPOSE: Prelens tear film stability of soft contact lens (SCL) play an important role for contact lens discomfort. In this study, we investigated the association between two types of noninvasive methods and evaluated the tear film stability with SCL using the methods. PATIENTS AND METHODS: In experiment 1, images of ring mire were recorded with a keratograph after focusing the pigment located at the front or back of the SCL. Interferometry and videokeratoscopy were used for the assessment of tear film stability in the right eye of 10 women, with two different cosmetic daily disposable SCLs: polymacon and etafilcon A with polyvinylpyrrolidone. Time to first distortion by noninvasive keratograph break up time (NIKBUT-first) was compared to noninvasive interferometry break up time (NIBUT). In experiment 2, ten normal females wore two different daily disposable SCLs: samfilcon A and narafilcon A. NIKBUT-first and NIBUT were compared between the lenses after 8 hours of SCL wearing. RESULTS: In experiment 1, NIBUT-first without SCL was significantly correlated to NIBUT without SCL (r=0.445, P=0.0488, Pearson's correlation coefficients). However, NIKBUT-first with SCL was not significantly correlated with NIBUT with SCL. In experiment 2, although NIKBUT-first was not significantly different between SCLs, samfilcon A had significantly longer NIBUT than narafilcon A (P=0.0315, paired t-test). CONCLUSION: NIKBUT-first with SCL could be related to tear film stability between the lens and the corneal surface, but not to prelens tear film stability. NIIBUT could be a suitable method to evaluate prelens tear stability.", "classifications": [ { "id": "Suzuki", "label": "Group Suzuki", "parent": "Takekawa", "type": "group" }, { "id": "Takekawa", "label": "Team Takekawa", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Takashi", "last_name": "Itokawa", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Hiroko", "last_name": "Iwashita", "name": null }, { "creator_type": "author", "first_name": "Yuichi", "last_name": "Hori", "name": null } ], "identifiers": { "doi": { "normalized": "10.2147/opth.s288047" }, "pmcid": { "normalized": "PMC7762444" }, "pmid": { "normalized": "33376300" } }, "mesh": [], "publication": { "conference_name": null, "date": "2020", "date_precision": "year", "issue": "", "normalized_date": "2020", "pages": "4459-4468", "proceedings_title": null, "publisher": "", "title": "Clinical ophthalmology (Auckland, N.Z.)", "volume": "14", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Comparison and Evaluation of Prelens Tear Film Stability by Different Noninvasive in vivo Methods.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Previous studies have suggested that histone methylation can modulate carcinogenesis and cancer progression. For instance, the histone methyltransferase SET and MYND domain containing 2 (SMYD2) is overexpressed in several types of cancer tissue. The aim of the present study was to determine whether SMYD2 could serve a therapeutic role in ovarian clear cell carcinoma (OCCC). Reverse transcription-quantitative PCR was used to examine SMYD2 expression in 23 clinical OCCC specimens. Moreover, OCCC cell proliferation and cell cycle progression were also examined following small interfering RNA-mediated SMYD2 silencing or treatment with a selective SMYD2 inhibitor. SMYD2 was significantly upregulated in clinical OCCC specimens, compared with normal ovarian tissue. In addition, SMYD2 knockdown decreased cell viability as determined via a Cell Counting Kit-8 assay. Moreover, the proportion of cells in the sub-G(1) phase increased following SMYD2 knockdown, suggesting increased apoptosis. Treatment with the SMYD2 inhibitor LLY-507 suppressed OCCC cell viability. These results suggested that SMYD2 could promote OCCC viability, and that SMYD2 inhibition induced apoptosis in these cells. Thus, SMYD2 inhibitors may represent a promising molecular targeted approach for OCCC treatment.", "classifications": [ { "id": "Hamamoto", "label": "Group Hamamoto", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Machiko", "last_name": "Kojima", "name": null }, { "creator_type": "author", "first_name": "Kenbun", "last_name": "Sone", "name": null }, { "creator_type": "author", "first_name": "Katsutoshi", "last_name": "Oda", "name": null }, { "creator_type": "author", "first_name": "Ryuji", "last_name": "Hamamoto", "name": null }, { "creator_type": "author", "first_name": "Syuzo", "last_name": "Kaneko", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Oki", "name": null }, { "creator_type": "author", "first_name": "Asako", "last_name": "Kukita", "name": null }, { "creator_type": "author", "first_name": "Akira", "last_name": "Kawata", "name": null }, { "creator_type": "author", "first_name": "Harunori", "last_name": "Honjoh", "name": null }, { "creator_type": "author", "first_name": "Yoshiko", "last_name": "Kawata", "name": null }, { "creator_type": "author", "first_name": "Tomoko", "last_name": "Kashiyama", "name": null }, { "creator_type": "author", "first_name": "Masakazu", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Ayumi", "last_name": "Taguchi", "name": null }, { "creator_type": "author", "first_name": "Yuichiro", "last_name": "Miyamoto", "name": null }, { "creator_type": "author", "first_name": "Michihiro", "last_name": "Tanikawa", "name": null }, { "creator_type": "author", "first_name": "Tetsushi", "last_name": "Tsuruga", "name": null }, { "creator_type": "author", "first_name": "Kazunori", "last_name": "Nagasaka", "name": null }, { "creator_type": "author", "first_name": "Osamu", "last_name": "Wada-Hiraike", "name": null }, { "creator_type": "author", "first_name": "Yutaka", "last_name": "Osuga", "name": null }, { "creator_type": "author", "first_name": "Tomoyuki", "last_name": "Fujii", "name": null } ], "identifiers": { "doi": { "normalized": "10.3892/ol.2020.12014" }, "pmcid": { "normalized": "PMC7471656" }, "pmid": { "normalized": "32934721" } }, "mesh": [], "publication": { "conference_name": null, "date": "2020 Nov", "date_precision": "unknown", "issue": "5", "normalized_date": null, "pages": "153", "proceedings_title": null, "publisher": "", "title": "Oncology letters", "volume": "20", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "The histone methyltransferase SMYD2 is a novel therapeutic target for the induction of apoptosis in ovarian clear cell carcinoma cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Single-cell RNA sequencing has enabled researchers to quantify the transcriptomes of individual cells, infer cell types and investigate differential expression among cell types, which will lead to a better understanding of the regulatory mechanisms of cell states. Transcript diversity caused by phenomena such as aberrant splicing events have been revealed, and differential expression of previously unannotated transcripts might be overlooked by annotation-based analyses. Accordingly, we have developed an approach to discover overlooked differentially expressed (DE) gene regions that complements annotation-based methods. Our algorithm decomposes mapped count data matrix for a gene region using non-negative matrix factorization, quantifies the differential expression level based on the decomposed matrix, and compares the differential expression level based on annotation-based approach to discover previously unannotated DE transcripts. We performed single-cell RNA sequencing for human neural stem cells and applied our algorithm to the dataset. We also applied our algorithm to two public single-cell RNA sequencing datasets correspond to mouse ES and primitive endoderm cells, and human preimplantation embryos. As a result, we discovered several intriguing DE transcripts, including a transcript related to the modulation of neural stem/progenitor cell differentiation.", "classifications": [ { "id": "Nikaido", "label": "Group Nikaido", "parent": "Fujiwara", "type": "group" }, { "id": "Fujiwara", "label": "Team Fujiwara", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Hirotaka", "last_name": "Matsumoto", "name": null }, { "creator_type": "author", "first_name": "Tetsutaro", "last_name": "Hayashi", "name": null }, { "creator_type": "author", "first_name": "Haruka", "last_name": "Ozaki", "name": null }, { "creator_type": "author", "first_name": "Koki", "last_name": "Tsuyuzaki", "name": null }, { "creator_type": "author", "first_name": "Mana", "last_name": "Umeda", "name": null }, { "creator_type": "author", "first_name": "Tsuyoshi", "last_name": "Iida", "name": null }, { "creator_type": "author", "first_name": "Masaya", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Hideyuki", "last_name": "Okano", "name": null }, { "creator_type": "author", "first_name": "Itoshi", "last_name": "Nikaido", "name": null } ], "identifiers": { "doi": { "normalized": "10.1093/nargab/lqz020" }, "pmcid": { "normalized": "PMC8499053" }, "pmid": { "normalized": "34632380" } }, "mesh": [], "publication": { "conference_name": null, "date": "2020 Mar", "date_precision": "unknown", "issue": "1", "normalized_date": null, "pages": "lqz020", "proceedings_title": null, "publisher": "", "title": "NAR genomics and bioinformatics", "volume": "2", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "An NMF-based approach to discover overlooked differentially expressed gene regions from single-cell RNA-seq data.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "DNAM-1 (CD226) is an activating immunoreceptor expressed on T cells and NK cells and involved in the pathogenesis of acute graft-versus-host disease (aGVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). We previously reported that a soluble form of DNAM-1 (sDNAM-1) is generated by shedding from activated T cells. Moreover, higher serum levels of sDNAM-1 in patients before allo-HSCT is a predictive biomarker for the development of aGVHD based on the retrospective univariate and multivariate analyses in allo-HSCT patients. However, it remains unclear how the serum levels of sDNAM-1 are regulated after allo-HSCT and whether they are associated with the development of aGVHD. Here, we constructed a mathematical model to assess the dynamics of sDNAM-1 after allo-HSCT by assuming that there are three types of sDNAM-1 (the first and the second were from alloreactive and non-alloreactive donor lymphocytes, respectively, and the third from recipient lymphocytes). Our mathematical model fitted well to the data set of sDNAM-1 in patients (n = 67) who had undergone allo-HSCT and suggest that the high proportion of the first type of sDNAM-1 to the total of the first and second types is associated with high risk of the development of severe aGVHD. Thus, sDNAM-1 after allo-HSCT can be a biomarker for the development of aGVHD.", "classifications": [ { "id": "Nagayama", "label": "Group Nagayama", "parent": "Fujiwara", "type": "group" }, { "id": "Fujiwara", "label": "Team Fujiwara", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yuki", "last_name": "Goshima", "name": null }, { "creator_type": "author", "first_name": "Shinji", "last_name": "Nakaoka", "name": null }, { "creator_type": "author", "first_name": "Kazuteru", "last_name": "Ohashi", "name": null }, { "creator_type": "author", "first_name": "Hisashi", "last_name": "Sakamaki", "name": null }, { "creator_type": "author", "first_name": "Kazuko", "last_name": "Shibuya", "name": null }, { "creator_type": "author", "first_name": "Akira", "last_name": "Shibuya", "name": null } ], "identifiers": { "doi": { "normalized": "10.1371/journal.pone.0228508" }, "pmcid": { "normalized": null }, "pmid": { "normalized": null } }, "mesh": [], "publication": { "conference_name": null, "date": "2020/02/10", "date_precision": "unknown", "issue": "2", "normalized_date": null, "pages": "e0228508", "proceedings_title": null, "publisher": "Public Library of Science", "title": "PLOS ONE", "volume": "15", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "A mathematical model for dynamics of soluble form of DNAM-1 as a biomarker for graft-versus-host disease", "url": "https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0228508", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Vascular smooth muscle cells (VSMCs) play a pivotal role in the stability and tonic regulation of vascular homeostasis. VSMCs can switch back and forth between highly proliferative (synthetic) and fully differentiated (contractile) phenotypes in response to changes in the vessel environment. Abnormal phenotypic switching of VSMCs is a distinctive characteristic of vascular disorders, including atherosclerosis, pulmonary hypertension, stroke, and peripheral artery disease; however, how the control of VSMC phenotypic switching is dysregulated under pathological conditions remains obscure. Canonical transient receptor potential (TRPC) channels have attracted attention as a key regulator of pathological phenotype switching in VSMCs. Several TRPC subfamily member proteins-especially TRPC1 and TRPC6-are upregulated in pathological VSMCs, and pharmacological inhibition of TRPC channel activity has been reported to improve hypertensive vascular remodeling in rodents. This review summarizes the current understanding of the role of TRPC channels in cardiovascular plasticity, including our recent finding that TRPC6 participates in aberrant VSMC phenotype switching under ischemic conditions, and discusses the therapeutic potential of TRPC channels.", "classifications": [ { "id": "Nishida", "label": "Group Nishida", "parent": "Nishida", "type": "group" }, { "id": "Nishimura", "label": "Group Nishimura", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Motohiro", "last_name": "Nishida", "name": null }, { "creator_type": "author", "first_name": "Tomohiro", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Supachoke", "last_name": "Mangmool", "name": null }, { "creator_type": "author", "first_name": "Kazuhiro", "last_name": "Nishiyama", "name": null }, { "creator_type": "author", "first_name": "Akiyuki", "last_name": "Nishimura", "name": null } ], "identifiers": { "doi": { "normalized": "10.12997/jla.2020.9.1.124" }, "pmcid": { "normalized": "PMC7379077" }, "pmid": { "normalized": "32821726" } }, "mesh": [], "publication": { "conference_name": null, "date": "2020 Jan", "date_precision": "unknown", "issue": "1", "normalized_date": null, "pages": "124-139", "proceedings_title": null, "publisher": "", "title": "Journal of lipid and atherosclerosis", "volume": "9", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Canonical Transient Receptor Potential Channels and Vascular Smooth Muscle Cell Plasticity.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Mitophagy is a critical process that safeguards mitochondrial quality control in order to maintain proper cellular homeostasis. Although the mitochondrial-anchored receptor Atg32-mediated cargo-recognition system has been well characterized to be essential for this process, the signaling pathway modulating its expression as a contribution of governing the mitophagy process remains largely unknown. Here, bioinformatics analyses of epigenetic or transcriptional regulators modulating gene expression allow us to identify the Paf1 complex (the polymerase-associated factor 1 complex, Paf1C) as a transcriptional repressor of ATG genes. We show that Paf1C suppresses glucose starvation-induced autophagy, but does not affect nitrogen starvation- or rapamycin-induced autophagy. Moreover, we show that Paf1C specifically regulates mitophagy through modulating ATG32 expression. Deletion of the genes encoding two core subunits of Paf1C, Paf1 and Ctr9, increases ATG32 and ATG11 expression and facilitates mitophagy activity. Although Paf1C is required for many histone modifications and gene activation, we show that Paf1C regulates mitophagy independent of its positive regulatory role in other processes. More importantly, we also demonstrate the mitophagic role of PAF1C in mammals. Overall, we conclude that Paf1C maintains mitophagy at a low level through binding the promoter of the ATG32 gene in glucose-rich conditions. Dissociation of Paf1C from ATG32 leads to the increased expression of this gene, and mitophagy induction upon glucose starvation. Thus, we uncover a new role of Paf1C in modulating the mitophagy process at the transcriptional level. ABBREVIATIONS: AMPK: AMP-activated protein kinase; ATP5F1A: ATP synthase F1 subunit alpha; CALCOCO2/NDP52: calcium binding and coiled-coil domain 2; CCCP: chlorophenylhydrazone; DFP: chelator deferiprone; GFP: green fluorescent protein; H2B-Ub1: H2B monoubiquitination; HSPD1/HSP60: heat shock protein family D (Hsp60) member 1; KD: kinase dead; OPTN, optineurin; Paf1: polymerase-associated factor 1; PINK1: PTEN induced kinase 1; PRKN/Parkin: parkin RBR E3 ubiquitin protein ligase; RT-qPCR: real-time quantitative PCR; SD-N: synthetic dropout without nitrogen base; TIMM23: translocase of inner mitochondrial membrane 23; TOMM20: translocase of outer mitochondrial membrane 20; WT: wild-type; YPD: yeast extract peptone dextrose; YPL: yeast extract peptone lactate.", "classifications": [ { "id": "Okamoto", "label": "Group Okamoto", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Liangde", "last_name": "Zheng", "name": null }, { "creator_type": "author", "first_name": "Wen-Jie", "last_name": "Shu", "name": null }, { "creator_type": "author", "first_name": "Yu-Min", "last_name": "Li", "name": null }, { "creator_type": "author", "first_name": "Muriel", "last_name": "Mari", "name": null }, { "creator_type": "author", "first_name": "Chaojun", "last_name": "Yan", "name": null }, { "creator_type": "author", "first_name": "Dehe", "last_name": "Wang", "name": null }, { "creator_type": "author", "first_name": "Zhao-Hong", "last_name": "Yin", "name": null }, { "creator_type": "author", "first_name": "Wei", "last_name": "Jiang", "name": null }, { "creator_type": "author", "first_name": "Yu", "last_name": "Zhou", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Okamoto", "name": null }, { "creator_type": "author", "first_name": "Fulvio", "last_name": "Reggiori", "name": null }, { "creator_type": "author", "first_name": "Daniel J.", "last_name": "Klionsky", "name": null }, { "creator_type": "author", "first_name": "Zhiyin", "last_name": "Song", "name": null }, { "creator_type": "author", "first_name": "Hai-Ning", "last_name": "Du", "name": null } ], "identifiers": { "doi": { "normalized": "10.1080/15548627.2019.1668228" }, "pmcid": { "normalized": "PMC7469518" }, "pmid": { "normalized": "31525119" } }, "mesh": [ { "descriptor": "Autophagy-Related Proteins", "descriptor_ui": "D000071183", "major_topic": false }, { "descriptor": "Gene Deletion", "descriptor_ui": "D017353", "major_topic": false }, { "descriptor": "Glucose", "descriptor_ui": "D005947", "major_topic": false }, { "descriptor": "Green Fluorescent Proteins", "descriptor_ui": "D049452", "major_topic": false }, { "descriptor": "HeLa Cells", "descriptor_ui": "D006367", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mitochondria", "descriptor_ui": "D008928", "major_topic": false }, { "descriptor": "Mitophagy", "descriptor_ui": "D063306", "major_topic": false }, { "descriptor": "Nitrogen", "descriptor_ui": "D009584", "major_topic": false }, { "descriptor": "Protein Subunits", "descriptor_ui": "D021122", "major_topic": false }, { "descriptor": "Receptors, Cytoplasmic and Nuclear", "descriptor_ui": "D018160", "major_topic": false }, { "descriptor": "Saccharomyces cerevisiae", "descriptor_ui": "D012441", "major_topic": false }, { "descriptor": "Saccharomyces cerevisiae Proteins", "descriptor_ui": "D029701", "major_topic": false }, { "descriptor": "Sirolimus", "descriptor_ui": "D020123", "major_topic": false }, { "descriptor": "Transcription Factors", "descriptor_ui": "D014157", "major_topic": false }, { "descriptor": "Transcription, Genetic", "descriptor_ui": "D014158", "major_topic": true }, { "descriptor": "Up-Regulation", "descriptor_ui": "D015854", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020 Aug", "date_precision": "unknown", "issue": "8", "normalized_date": null, "pages": "1366-1379", "proceedings_title": null, "publisher": "", "title": "Autophagy", "volume": "16", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "The Paf1 complex transcriptionally regulates the mitochondrial-anchored protein Atg32 leading to activation of mitophagy.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "TAZ (transcriptional coactivator with PDZ-binding motif) and YAP (Yes-associated protein) are key molecules of the Hippo pathway. Recent studies revealed that these molecules are essential in lung development; however, the precise signaling cascade involving these molecules and the differences in their roles during lung development remain unknown. We aimed to investigate YAP and TAZ functions using lung epithelium-specific Taz and Yap conditional knockout mice. We generated lung epithelium-specific Taz and Yap conditional knockout mice and investigated the functions of YAP and TAZ in lung development. Selective TAZ deficiency in mouse lung epithelial cells resulted in abnormal alveolarization, which mimics lung emphysema, in adults, whereas YAP deficiency caused disruption of bronchial morphogenesis during the embryonic stage. We report that TAZ and YAP are sequentially expressed in the lung and that this could explain their different phenotypes. Furthermore, we report that YAP stimulates Shh (Sonic hedgehog) expression and regulates the FGF (fibroblast growth factor)-SHH feedback loop, thereby contributing to normal bronchial morphogenesis. We also found that TGF-beta (transforming growth factor-beta) stimulation induced Shh expression in the lung epithelial cells, and both TAZ and YAP are essential in this novel pathway. Our results provide a novel insight into the molecular mechanisms underlying lung development and contribute to a better understanding of the characteristics of TAZ and YAP.", "classifications": [ { "id": "Hamamoto", "label": "Group Hamamoto", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Hideaki", "last_name": "Isago", "name": null }, { "creator_type": "author", "first_name": "Akihisa", "last_name": "Mitani", "name": null }, { "creator_type": "author", "first_name": "Yu", "last_name": "Mikami", "name": null }, { "creator_type": "author", "first_name": "Masafumi", "last_name": "Horie", "name": null }, { "creator_type": "author", "first_name": "Hirokazu", "last_name": "Urushiyama", "name": null }, { "creator_type": "author", "first_name": "Ryuji", "last_name": "Hamamoto", "name": null }, { "creator_type": "author", "first_name": "Yasuhiro", "last_name": "Terasaki", "name": null }, { "creator_type": "author", "first_name": "Takahide", "last_name": "Nagase", "name": null } ], "identifiers": { "doi": { "normalized": "10.1165/rcmb.2019-0218oc" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "31486675" } }, "mesh": [ { "descriptor": "Adaptor Proteins, Signal Transducing", "descriptor_ui": "D048868", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Cycle Proteins", "descriptor_ui": "D018797", "major_topic": false }, { "descriptor": "Hedgehog Proteins", "descriptor_ui": "D053823", "major_topic": false }, { "descriptor": "Intracellular Signaling Peptides and Proteins", "descriptor_ui": "D047908", "major_topic": false }, { "descriptor": "Lung", "descriptor_ui": "D008168", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Organogenesis", "descriptor_ui": "D038081", "major_topic": false }, { "descriptor": "Phosphoproteins", "descriptor_ui": "D010750", "major_topic": false }, { "descriptor": "Protein Serine-Threonine Kinases", "descriptor_ui": "D017346", "major_topic": false }, { "descriptor": "Proto-Oncogene Proteins c-yes", "descriptor_ui": "D051575", "major_topic": false }, { "descriptor": "Trans-Activators", "descriptor_ui": "D015534", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020 Feb", "date_precision": "unknown", "issue": "2", "normalized_date": null, "pages": "256-266", "proceedings_title": null, "publisher": "", "title": "American journal of respiratory cell and molecular biology", "volume": "62", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Epithelial Expression of YAP and TAZ Is Sequentially Required in Lung Development.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND AND AIMS: Dysfunctional hepatic lipid metabolism is a cause of nonalcoholic fatty liver disease (NAFLD), the most common chronic liver disorder worldwide, and is closely associated with insulin resistance and type 2 diabetes. ELOVL fatty acid elongase 6 (Elovl6) is responsible for converting C16 saturated and monounsaturated fatty acids (FAs) into C18 species. We have previously shown that Elovl6 contributes to obesity-induced insulin resistance by modifying hepatic C16/C18-related FA composition. APPROACH AND RESULTS: To define the precise molecular mechanism by which hepatic Elovl6 affects energy homeostasis and metabolic disease, we generated liver-specific Elovl6 knockout (LKO) mice. Unexpectedly, LKO mice were not protected from high-fat diet-induced insulin resistance. Instead, LKO mice exhibited higher insulin sensitivity than controls when consuming a high-sucrose diet (HSD), which induces lipogenesis. Hepatic patatin-like phospholipase domain-containing protein 3 (Pnpla3) expression was down-regulated in LKO mice, and adenoviral Pnpla3 restoration reversed the enhancement in insulin sensitivity in HSD-fed LKO mice. Lipidomic analyses showed that the hepatic ceramide(d18:1/18:0) content was lower in LKO mice, which may explain the effect on insulin sensitivity. Ceramide(d18:1/18:0) enhances protein phosphatase 2A (PP2A) activity by interfering with the binding of PP2A to inhibitor 2 of PP2A, leading to Akt dephosphorylation. Its production involves the formation of an Elovl6-ceramide synthase 4 (CerS4) complex in the endoplasmic reticulum and a Pnpla3-CerS4 complex on lipid droplets. Consistent with this, liver-specific Elovl6 deletion in ob/ob mice reduced both hepatic ceramide(d18:1/18:0) and PP2A activity and ameliorated insulin resistance. CONCLUSIONS: Our study demonstrates the key role of hepatic Elovl6 in the regulation of the acyl-chain composition of ceramide and that C18:0-ceramide is a potent regulator of hepatic insulin signaling linked to Pnpla3-mediated NAFLD.", "classifications": [ { "id": "Miyamoto", "label": "Group Miyamoto", "parent": "Wakamoto", "type": "group" }, { "id": "Wakamoto", "label": "Team Wakamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Takashi", "last_name": "Matsuzaka", "name": null }, { "creator_type": "author", "first_name": "Motoko", "last_name": "Kuba", "name": null }, { "creator_type": "author", "first_name": "Saori", "last_name": "Koyasu", "name": null }, { "creator_type": "author", "first_name": "Yuta", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Kaori", "last_name": "Motomura", "name": null }, { "creator_type": "author", "first_name": "Sundaram", "last_name": "Arulmozhiraja", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Ohno", "name": null }, { "creator_type": "author", "first_name": "Rahul", "last_name": "Sharma", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Shimura", "name": null }, { "creator_type": "author", "first_name": "Yuka", "last_name": "Okajima", "name": null }, { "creator_type": "author", "first_name": "Song-Iee", "last_name": "Han", "name": null }, { "creator_type": "author", "first_name": "Yuichi", "last_name": "Aita", "name": null }, { "creator_type": "author", "first_name": "Yuhei", "last_name": "Mizunoe", "name": null }, { "creator_type": "author", "first_name": "Yoshinori", "last_name": "Osaki", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Iwasaki", "name": null }, { "creator_type": "author", "first_name": "Shigeru", "last_name": "Yatoh", "name": null }, { "creator_type": "author", "first_name": "Hiroaki", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Hirohito", "last_name": "Sone", "name": null }, { "creator_type": "author", "first_name": "Yoshinori", "last_name": "Takeuchi", "name": null }, { "creator_type": "author", "first_name": "Naoya", "last_name": "Yahagi", "name": null }, { "creator_type": "author", "first_name": "Takafumi", "last_name": "Miyamoto", "name": null }, { "creator_type": "author", "first_name": "Motohiro", "last_name": "Sekiya", "name": null }, { "creator_type": "author", "first_name": "Yoshimi", "last_name": "Nakagawa", "name": null }, { "creator_type": "author", "first_name": "Masatsugu", "last_name": "Ema", "name": null }, { "creator_type": "author", "first_name": "Satoru", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Hiroaki", "last_name": "Tokiwa", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Shimano", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/hep.30953" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "31529722" } }, "mesh": [ { "descriptor": "Acyltransferases", "descriptor_ui": "D000217", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Ceramides", "descriptor_ui": "D002518", "major_topic": false }, { "descriptor": "Dietary Sucrose", "descriptor_ui": "D019422", "major_topic": false }, { "descriptor": "Down-Regulation", "descriptor_ui": "D015536", "major_topic": false }, { "descriptor": "Fatty Acid Elongases", "descriptor_ui": "D000081031", "major_topic": false }, { "descriptor": "Insulin Resistance", "descriptor_ui": "D007333", "major_topic": false }, { "descriptor": "Liver", "descriptor_ui": "D008099", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Non-alcoholic Fatty Liver Disease", "descriptor_ui": "D065626", "major_topic": false }, { "descriptor": "Phospholipases A2, Calcium-Independent", "descriptor_ui": "D054512", "major_topic": false }, { "descriptor": "Protein Phosphatase 2", "descriptor_ui": "D054648", "major_topic": false }, { "descriptor": "Sphingosine N-Acyltransferase", "descriptor_ui": "D051049", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020 May", "date_precision": "unknown", "issue": "5", "normalized_date": null, "pages": "1609-1625", "proceedings_title": null, "publisher": "", "title": "Hepatology (Baltimore, Md.)", "volume": "71", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Hepatocyte ELOVL Fatty Acid Elongase 6 Determines Ceramide Acyl-Chain Length and Hepatic Insulin Sensitivity in Mice.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "We investigated whether genetic susceptibility to tuberculosis (TB) influences lung adenocarcinoma development among never-smokers using TB genome-wide association study (GWAS) results within the Female Lung Cancer Consortium in Asia. Pathway analysis with the adaptive rank truncated product method was used to assess the association between a TB-related gene-set and lung adenocarcinoma using GWAS data from 5512 lung adenocarcinoma cases and 6277 controls. The gene-set consisted of 31 genes containing known/suggestive associations with genetic variants from previous TB-GWAS. Subsequently, we followed-up with Mendelian Randomization to evaluate the association between TB and lung adenocarcinoma using three genome-wide significant variants from previous TB-GWAS in East Asians. The TB-related gene-set was associated with lung adenocarcinoma (p = 0.016). Additionally, the Mendelian Randomization showed an association between TB and lung adenocarcinoma (OR = 1.31, 95% CI: 1.03, 1.66, p = 0.027). Our findings support TB as a causal risk factor for lung cancer development among never-smoking Asian women.", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Jason Y. Y.", "last_name": "Wong", "name": null }, { "creator_type": "author", "first_name": "Han", "last_name": "Zhang", "name": null }, { "creator_type": "author", "first_name": "Chao A.", "last_name": "Hsiung", "name": null }, { "creator_type": "author", "first_name": "Kouya", "last_name": "Shiraishi", "name": null }, { "creator_type": "author", "first_name": "Kai", "last_name": "Yu", "name": null }, { "creator_type": "author", "first_name": "Keitaro", "last_name": "Matsuo", "name": null }, { "creator_type": "author", "first_name": "Maria Pik", "last_name": "Wong", "name": null }, { "creator_type": "author", "first_name": "Yun-Chul", "last_name": "Hong", "name": null }, { "creator_type": "author", "first_name": "Jiucun", "last_name": "Wang", "name": null }, { "creator_type": "author", "first_name": "Wei Jie", "last_name": "Seow", "name": null }, { "creator_type": "author", "first_name": "Zhaoming", "last_name": "Wang", "name": null }, { "creator_type": "author", "first_name": "Minsun", "last_name": "Song", "name": null }, { "creator_type": "author", "first_name": "Hee Nam", "last_name": "Kim", "name": null }, { "creator_type": "author", "first_name": "I.-Shou", "last_name": "Chang", "name": null }, { "creator_type": "author", "first_name": "Nilanjan", "last_name": "Chatterjee", "name": null }, { "creator_type": "author", "first_name": "Wei", "last_name": "Hu", "name": null }, { "creator_type": "author", "first_name": "Chen", "last_name": "Wu", "name": null }, { "creator_type": "author", "first_name": "Tetsuya", "last_name": "Mitsudomi", "name": null }, { "creator_type": "author", "first_name": "Wei", "last_name": "Zheng", "name": null }, { "creator_type": "author", "first_name": "Jin Hee", "last_name": "Kim", "name": null }, { "creator_type": "author", "first_name": "Adeline", "last_name": "Seow", "name": null }, { "creator_type": "author", "first_name": "Neil E.", "last_name": "Caporaso", "name": null }, { "creator_type": "author", "first_name": "Min-Ho", "last_name": "Shin", "name": null }, { "creator_type": "author", "first_name": "Lap Ping", "last_name": "Chung", "name": null }, { "creator_type": "author", "first_name": "She-Juan", "last_name": "An", "name": null }, { "creator_type": "author", "first_name": "Ping", "last_name": "Wang", "name": null }, { "creator_type": "author", "first_name": "Yang", "last_name": "Yang", "name": null }, { "creator_type": "author", "first_name": "Hong", "last_name": "Zheng", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null }, { "creator_type": "author", "first_name": "Xu-Chao", "last_name": "Zhang", "name": null }, { "creator_type": "author", "first_name": "Young Tae", "last_name": "Kim", "name": null }, { "creator_type": "author", "first_name": "Qiuyin", "last_name": "Cai", "name": null }, { "creator_type": "author", "first_name": "Zhihua", "last_name": "Yin", "name": null }, { "creator_type": "author", "first_name": "Young-Chul", "last_name": "Kim", "name": null }, { "creator_type": "author", "first_name": "Bryan A.", "last_name": "Bassig", "name": null }, { "creator_type": "author", "first_name": "Jiang", "last_name": "Chang", "name": null }, { "creator_type": "author", "first_name": "James Chung Man", "last_name": "Ho", "name": null }, { "creator_type": "author", "first_name": "Bu-Tian", "last_name": "Ji", "name": null }, { "creator_type": "author", "first_name": "Yataro", "last_name": "Daigo", "name": null }, { "creator_type": "author", "first_name": "Hidemi", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Yukihide", "last_name": "Momozawa", "name": null }, { "creator_type": "author", "first_name": "Kyota", "last_name": "Ashikawa", "name": null }, { "creator_type": "author", "first_name": "Yoichiro", "last_name": "Kamatani", "name": null }, { "creator_type": "author", "first_name": "Takayuki", "last_name": "Honda", "name": null }, { "creator_type": "author", "first_name": "H. Dean", "last_name": "Hosgood", "name": null }, { "creator_type": "author", "first_name": "Hiromi", "last_name": "Sakamoto", "name": null }, { "creator_type": "author", "first_name": "Hideo", "last_name": "Kunitoh", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Tsuta", "name": null }, { "creator_type": "author", "first_name": "Shun-Ichi", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Michiaki", "last_name": "Kubo", "name": null }, { "creator_type": "author", "first_name": "Yohei", "last_name": "Miyagi", "name": null }, { "creator_type": "author", "first_name": "Haruhiko", "last_name": "Nakayama", "name": null }, { "creator_type": "author", "first_name": "Shingo", "last_name": "Matsumoto", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Tsuboi", "name": null }, { "creator_type": "author", "first_name": "Koichi", "last_name": "Goto", "name": null }, { "creator_type": "author", "first_name": "Jianxin", "last_name": "Shi", "name": null }, { "creator_type": "author", "first_name": "Lei", "last_name": "Song", "name": null }, { "creator_type": "author", "first_name": "Xing", "last_name": "Hua", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Akiteru", "last_name": "Goto", "name": null }, { "creator_type": "author", "first_name": "Yoshihiro", "last_name": "Minamiya", "name": null }, { "creator_type": "author", "first_name": "Kimihiro", "last_name": "Shimizu", "name": null }, { "creator_type": "author", "first_name": "Kazumi", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Fusheng", "last_name": "Wei", "name": null }, { "creator_type": "author", "first_name": "Fumihiko", "last_name": "Matsuda", "name": null }, { "creator_type": "author", "first_name": "Jian", "last_name": "Su", "name": null }, { "creator_type": "author", "first_name": "Yeul Hong", "last_name": "Kim", "name": null }, { "creator_type": "author", "first_name": "In-Jae", "last_name": "Oh", "name": null }, { "creator_type": "author", "first_name": "Fengju", "last_name": "Song", "name": null }, { "creator_type": "author", "first_name": "Wu-Chou", "last_name": "Su", "name": null }, { "creator_type": "author", "first_name": "Yu-Min", "last_name": "Chen", "name": null }, { "creator_type": "author", "first_name": "Gee-Chen", "last_name": "Chang", "name": null }, { "creator_type": "author", "first_name": "Kuan-Yu", "last_name": "Chen", "name": null }, { "creator_type": "author", "first_name": "Ming-Shyan", "last_name": "Huang", "name": null }, { "creator_type": "author", "first_name": "Li-Hsin", "last_name": "Chien", "name": null }, { "creator_type": "author", "first_name": "Yong-Bing", "last_name": "Xiang", "name": null }, { "creator_type": "author", "first_name": "Jae Yong", "last_name": "Park", "name": null }, { "creator_type": "author", "first_name": "Sun-Seog", "last_name": "Kweon", "name": null }, { "creator_type": "author", "first_name": "Chien-Jen", "last_name": "Chen", "name": null }, { "creator_type": "author", "first_name": "Kyoung-Mu", "last_name": "Lee", "name": null }, { "creator_type": "author", "first_name": "Batel", "last_name": "Blechter", "name": null }, { "creator_type": "author", "first_name": "Haixin", "last_name": "Li", "name": null }, { "creator_type": "author", "first_name": "Yu-Tang", "last_name": "Gao", "name": null }, { "creator_type": "author", "first_name": "Biyun", "last_name": "Qian", "name": null }, { "creator_type": "author", "first_name": "Daru", "last_name": "Lu", "name": null }, { "creator_type": "author", "first_name": "Jianjun", "last_name": "Liu", "name": null }, { "creator_type": "author", "first_name": "Hyo-Sung", "last_name": "Jeon", "name": null }, { "creator_type": "author", "first_name": "Chin-Fu", "last_name": "Hsiao", "name": null }, { "creator_type": "author", "first_name": "Jae Sook", "last_name": "Sung", "name": null }, { "creator_type": "author", "first_name": "Ying-Huang", "last_name": "Tsai", "name": null }, { "creator_type": "author", "first_name": "Yoo Jin", "last_name": "Jung", "name": null }, { "creator_type": "author", "first_name": "Huan", "last_name": "Guo", "name": null }, { "creator_type": "author", "first_name": "Zhibin", "last_name": "Hu", "name": null }, { "creator_type": "author", "first_name": "Wen-Chang", "last_name": "Wang", "name": null }, { "creator_type": "author", "first_name": "Charles C.", "last_name": "Chung", "name": null }, { "creator_type": "author", "first_name": "Laurie", "last_name": "Burdett", "name": null }, { "creator_type": "author", "first_name": "Meredith", "last_name": "Yeager", "name": null }, { "creator_type": "author", "first_name": "Amy", "last_name": "Hutchinson", "name": null }, { "creator_type": "author", "first_name": "Sonja I.", "last_name": "Berndt", "name": null }, { "creator_type": "author", "first_name": "Wei", "last_name": "Wu", "name": null }, { "creator_type": "author", "first_name": "Herbert", "last_name": "Pang", "name": null }, { "creator_type": "author", "first_name": "Yuqing", "last_name": "Li", "name": null }, { "creator_type": "author", "first_name": "Jin Eun", "last_name": "Choi", "name": null }, { "creator_type": "author", "first_name": "Kyong Hwa", "last_name": "Park", "name": null }, { "creator_type": "author", "first_name": "Sook Whan", "last_name": "Sung", "name": null }, { "creator_type": "author", "first_name": "Li", "last_name": "Liu", "name": null }, { "creator_type": "author", "first_name": "C. H.", "last_name": "Kang", "name": null }, { "creator_type": "author", "first_name": "Meng", "last_name": "Zhu", "name": null }, { "creator_type": "author", "first_name": "Chung-Hsing", "last_name": "Chen", "name": null }, { "creator_type": "author", "first_name": "Tsung-Ying", "last_name": "Yang", "name": null }, { "creator_type": "author", "first_name": "Jun", "last_name": "Xu", "name": null }, { "creator_type": "author", "first_name": "Peng", "last_name": "Guan", "name": null }, { "creator_type": "author", "first_name": "Wen", "last_name": "Tan", "name": null }, { "creator_type": "author", "first_name": "Chih-Liang", "last_name": "Wang", "name": null }, { "creator_type": "author", "first_name": "Michael", "last_name": "Hsin", "name": null }, { "creator_type": "author", "first_name": "Ko-Yung", "last_name": "Sit", "name": null }, { "creator_type": "author", "first_name": "James", "last_name": "Ho", "name": null }, { "creator_type": "author", "first_name": "Ying", "last_name": "Chen", "name": null }, { "creator_type": "author", "first_name": "Yi Young", "last_name": "Choi", "name": null }, { "creator_type": "author", "first_name": "Jen-Yu", "last_name": "Hung", "name": null }, { "creator_type": "author", "first_name": "Jun Suk", "last_name": "Kim", "name": null }, { "creator_type": "author", "first_name": "Ho Il", "last_name": "Yoon", "name": null }, { "creator_type": "author", "first_name": "Chien-Chung", "last_name": "Lin", "name": null }, { "creator_type": "author", "first_name": "In Kyu", "last_name": "Park", "name": null }, { "creator_type": "author", "first_name": "Ping", "last_name": "Xu", "name": null }, { "creator_type": "author", "first_name": "Yuzhuo", "last_name": "Wang", "name": null }, { "creator_type": "author", "first_name": "Qincheng", "last_name": "He", "name": null }, { "creator_type": "author", "first_name": "Reury-Perng", "last_name": "Perng", "name": null }, { "creator_type": "author", "first_name": "Chih-Yi", "last_name": "Chen", "name": null }, { "creator_type": "author", "first_name": "Roel", "last_name": "Vermeulen", "name": null }, { "creator_type": "author", "first_name": "Junjie", "last_name": "Wu", "name": null }, { "creator_type": "author", "first_name": "Wei-Yen", "last_name": "Lim", "name": null }, { "creator_type": "author", "first_name": "Kun-Chieh", "last_name": "Chen", "name": null }, { "creator_type": "author", "first_name": "Yao-Jen", "last_name": "Li", "name": null }, { "creator_type": "author", "first_name": "Jihua", "last_name": "Li", "name": null }, { "creator_type": "author", "first_name": "Hongyan", "last_name": "Chen", "name": null }, { "creator_type": "author", "first_name": "Chong-Jen", "last_name": "Yu", "name": null }, { "creator_type": "author", "first_name": "Li", "last_name": "Jin", "name": null }, { "creator_type": "author", "first_name": "Tzu-Yu", "last_name": "Chen", "name": null }, { "creator_type": "author", "first_name": "Shih-Sheng", "last_name": "Jiang", "name": null }, { "creator_type": "author", "first_name": "Jie", "last_name": "Liu", "name": null }, { "creator_type": "author", "first_name": "Taiki", "last_name": "Yamaji", "name": null }, { "creator_type": "author", "first_name": "Belynda", "last_name": "Hicks", "name": null }, { "creator_type": "author", "first_name": "Kathleen", "last_name": "Wyatt", "name": null }, { "creator_type": "author", "first_name": "Shengchao A.", "last_name": "Li", "name": null }, { "creator_type": "author", "first_name": "Juncheng", "last_name": "Dai", "name": null }, { "creator_type": "author", "first_name": "Hongxia", "last_name": "Ma", "name": null }, { "creator_type": "author", "first_name": "Guangfu", "last_name": "Jin", "name": null }, { "creator_type": "author", "first_name": "Bao", "last_name": "Song", "name": null }, { "creator_type": "author", "first_name": "Zhehai", "last_name": "Wang", "name": null }, { "creator_type": "author", "first_name": "Sensen", "last_name": "Cheng", "name": null }, { "creator_type": "author", "first_name": "Xuelian", "last_name": "Li", "name": null }, { "creator_type": "author", "first_name": "Yangwu", "last_name": "Ren", "name": null }, { "creator_type": "author", "first_name": "Ping", "last_name": "Cui", "name": null }, { "creator_type": "author", "first_name": "Motoki", "last_name": "Iwasaki", "name": null }, { "creator_type": "author", "first_name": "Taichi", "last_name": "Shimazu", "name": null }, { "creator_type": "author", "first_name": "Shoichiro", "last_name": "Tsugane", "name": null }, { "creator_type": "author", "first_name": "Junjie", "last_name": "Zhu", "name": null }, { "creator_type": "author", "first_name": "Ying", "last_name": "Chen", "name": null }, { "creator_type": "author", "first_name": "Kaiyun", "last_name": "Yang", "name": null }, { "creator_type": "author", "first_name": "Gening", "last_name": "Jiang", "name": null }, { "creator_type": "author", "first_name": "Ke", "last_name": "Fei", "name": null }, { "creator_type": "author", "first_name": "Guoping", "last_name": "Wu", "name": null }, { "creator_type": "author", "first_name": "Hsien-Chin", "last_name": "Lin", "name": null }, { "creator_type": "author", "first_name": "Hui-Ling", "last_name": "Chen", "name": null }, { "creator_type": "author", "first_name": "Yao-Huei", "last_name": "Fang", "name": null }, { "creator_type": "author", "first_name": "Fang-Yu", "last_name": "Tsai", "name": null }, { "creator_type": "author", "first_name": "Wan-Shan", "last_name": "Hsieh", "name": null }, { "creator_type": "author", "first_name": "Jinming", "last_name": "Yu", "name": null }, { "creator_type": "author", "first_name": "Victoria L.", "last_name": "Stevens", "name": null }, { "creator_type": "author", "first_name": "Ite A.", "last_name": "Laird-Offringa", "name": null }, { "creator_type": "author", "first_name": "Crystal N.", "last_name": "Marconett", "name": null }, { "creator_type": "author", "first_name": "Linda", "last_name": "Rieswijk", "name": null }, { "creator_type": "author", "first_name": "Ann", "last_name": "Chao", "name": null }, { "creator_type": "author", "first_name": "Pan-Chyr", "last_name": "Yang", "name": null }, { "creator_type": "author", "first_name": "Xiao-Ou", "last_name": "Shu", "name": null }, { "creator_type": "author", "first_name": "Tangchun", "last_name": "Wu", "name": null }, { "creator_type": "author", "first_name": "Y. L.", "last_name": "Wu", "name": null }, { "creator_type": "author", "first_name": "Dongxin", "last_name": "Lin", "name": null }, { "creator_type": "author", "first_name": "Kexin", "last_name": "Chen", "name": null }, { "creator_type": "author", "first_name": "Baosen", "last_name": "Zhou", "name": null }, { "creator_type": "author", "first_name": "Yun-Chao", "last_name": "Huang", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Kohno", "name": null }, { "creator_type": "author", "first_name": "Hongbing", "last_name": "Shen", "name": null }, { "creator_type": "author", "first_name": "Stephen J.", "last_name": "Chanock", "name": null }, { "creator_type": "author", "first_name": "Nathaniel", "last_name": "Rothman", "name": null }, { "creator_type": "author", "first_name": "Qing", "last_name": "Lan", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.ygeno.2019.07.008" }, "pmcid": { "normalized": "PMC6954985" }, "pmid": { "normalized": "31306748" } }, "mesh": [ { "descriptor": "Adenocarcinoma of Lung", "descriptor_ui": "D000077192", "major_topic": false }, { "descriptor": "Asian People", "descriptor_ui": "D044466", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Genome-Wide Association Study", "descriptor_ui": "D055106", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Lung Neoplasms", "descriptor_ui": "D008175", "major_topic": false }, { "descriptor": "Mendelian Randomization Analysis", "descriptor_ui": "D057182", "major_topic": false }, { "descriptor": "Non-Smokers", "descriptor_ui": "D000078405", "major_topic": false }, { "descriptor": "Tuberculosis, Pulmonary", "descriptor_ui": "D014397", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020 Mar", "date_precision": "unknown", "issue": "2", "normalized_date": null, "pages": "1223-1232", "proceedings_title": null, "publisher": "", "title": "Genomics", "volume": "112", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Tuberculosis infection and lung adenocarcinoma: Mendelian randomization and pathway analysis of genome-wide association study data from never-smoking Asian women.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Immune checkpoint inhibitor (ICI) therapies have revolutionized the management of patients with NSCLC and have led to unprecedented improvements in response rates and survival in a subset of patients with this fatal disease. However, the available therapies work only for a minority of patients, are associated with substantial societal cost, and may lead to considerable immune-related adverse events. Therefore, patient selection must be optimized through the use of relevant biomarkers. Programmed death-ligand 1 protein expression by immunohistochemistry is widely used today for the selection of programmed cell death protein 1 inhibitor therapy in patients with NSCLC; however, this approach lacks robust sensitivity and specificity for predicting response. Tumor mutation burden (TMB), or the number of somatic mutations derived from next-generation sequencing techniques, has been widely explored as an alternative or complementary biomarker for response to ICIs. In theory, a higher TMB increases the probability of tumor neoantigen production and therefore, the likelihood of immune recognition and tumor cell killing. Although TMB alone is a simplistic surrogate of this complex interplay, it is a quantitative variable that can be relatively readily measured using currently available sequencing techniques. A large number of clinical trials and retrospective analyses, employing both tumor and blood-based sequencing tools, have evaluated the performance of TMB as a predictive biomarker, and in many cases reveal a correlation between high TMB and ICI response rates and progression-free survival. Many challenges remain before the implementation of TMB as a biomarker in clinical practice. These include the following: (1) identification of therapies whose response is best informed by TMB status; (2) robust definition of a predictive TMB cut point; (3) acceptable sequencing panel size and design; and (4) the need for robust technical and informatic rigor to generate precise and accurate TMB measurements across different laboratories. Finally, effective prediction of response to ICI therapy will likely require integration of TMB with a host of other potential biomarkers, including tumor genomic driver alterations, tumor-immune milieu, and other features of the host immune system. This perspective piece will review the current clinical evidence for TMB as a biomarker and address the technical sequencing considerations and ongoing challenges in the use of TMB in routine practice.", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Lynette M.", "last_name": "Sholl", "name": null }, { "creator_type": "author", "first_name": "Fred R.", "last_name": "Hirsch", "name": null }, { "creator_type": "author", "first_name": "David", "last_name": "Hwang", "name": null }, { "creator_type": "author", "first_name": "Johan", "last_name": "Botling", "name": null }, { "creator_type": "author", "first_name": "Fernando", "last_name": "Lopez-Rios", "name": null }, { "creator_type": "author", "first_name": "Lukas", "last_name": "Bubendorf", "name": null }, { "creator_type": "author", "first_name": "Mari", "last_name": "Mino-Kenudson", "name": null }, { "creator_type": "author", "first_name": "Anja C.", "last_name": "Roden", "name": null }, { "creator_type": "author", "first_name": "Mary Beth", "last_name": "Beasley", "name": null }, { "creator_type": "author", "first_name": "Alain", "last_name": "Borczuk", "name": null }, { "creator_type": "author", "first_name": "Elisabeth", "last_name": "Brambilla", "name": null }, { "creator_type": "author", "first_name": "Gang", "last_name": "Chen", "name": null }, { "creator_type": "author", "first_name": "Teh-Ying", "last_name": "Chou", "name": null }, { "creator_type": "author", "first_name": "Jin-Haeng", "last_name": "Chung", "name": null }, { "creator_type": "author", "first_name": "Wendy A.", "last_name": "Cooper", "name": null }, { "creator_type": "author", "first_name": "Sanja", "last_name": "Dacic", "name": null }, { "creator_type": "author", "first_name": "Sylvie", "last_name": "Lantuejoul", "name": null }, { "creator_type": "author", "first_name": "Deepali", "last_name": "Jain", "name": null }, { "creator_type": "author", "first_name": "Dongmei", "last_name": "Lin", "name": null }, { "creator_type": "author", "first_name": "Yuko", "last_name": "Minami", "name": null }, { "creator_type": "author", "first_name": "Andre", "last_name": "Moreira", "name": null }, { "creator_type": "author", "first_name": "Andrew G.", "last_name": "Nicholson", "name": null }, { "creator_type": "author", "first_name": "Masayuki", "last_name": "Noguchi", "name": null }, { "creator_type": "author", "first_name": "Mauro", "last_name": "Papotti", "name": null }, { "creator_type": "author", "first_name": "Giuseppe", "last_name": "Pelosi", "name": null }, { "creator_type": "author", "first_name": "Claudia", "last_name": "Poleri", "name": null }, { "creator_type": "author", "first_name": "Natasha", "last_name": "Rekhtman", "name": null }, { "creator_type": "author", "first_name": "Ming-Sound", "last_name": "Tsao", "name": null }, { "creator_type": "author", "first_name": "Erik", "last_name": "Thunnissen", "name": null }, { "creator_type": "author", "first_name": "William", "last_name": "Travis", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null }, { "creator_type": "author", "first_name": "Akihiko", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Jillian B.", "last_name": "Daigneault", "name": null }, { "creator_type": "author", "first_name": "Ahmet", "last_name": "Zehir", "name": null }, { "creator_type": "author", "first_name": "Solange", "last_name": "Peters", "name": null }, { "creator_type": "author", "first_name": "Ignacio I.", "last_name": "Wistuba", "name": null }, { "creator_type": "author", "first_name": "Keith M.", "last_name": "Kerr", "name": null }, { "creator_type": "author", "first_name": "John W.", "last_name": "Longshore", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.jtho.2020.05.019" }, "pmcid": { "normalized": "PMC8363213" }, "pmid": { "normalized": "32522712" } }, "mesh": [ { "descriptor": "Carcinoma, Non-Small-Cell Lung", "descriptor_ui": "D002289", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Immunotherapy", "descriptor_ui": "D007167", "major_topic": false }, { "descriptor": "Lung Neoplasms", "descriptor_ui": "D008175", "major_topic": true }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": false }, { "descriptor": "Retrospective Studies", "descriptor_ui": "D012189", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020 Sep", "date_precision": "unknown", "issue": "9", "normalized_date": null, "pages": "1409-1424", "proceedings_title": null, "publisher": "", "title": "Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer", "volume": "15", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "The Promises and Challenges of Tumor Mutation Burden as an Immunotherapy Biomarker: A Perspective from the International Association for the Study of Lung Cancer Pathology Committee.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "During muscle regeneration, extracellular signal-regulated kinase (ERK) promotes both proliferation and migration. However, the relationship between proliferation and migration is poorly understood in this context. To elucidate this complex relationship on a physiological level, we established an intravital imaging system for measuring ERK activity, migration speed, and cell-cycle phases in mouse muscle satellite cell-derived myogenic cells. We found that in vivo, ERK is maximally activated in myogenic cells two days after injury, and this is then followed by increases in cell number and motility. With limited effects of ERK activity on migration on an acute timescale, we hypothesized that ERK increases migration speed in the later phase by promoting cell-cycle progression. Our cell-cycle analysis further revealed that in myogenic cells, ERK activity is critical for G1/S transition, and cells migrate more rapidly in S/G2 phase 3 days after injury. Finally, migration speed of myogenic cells was suppressed after CDK1/2-but not CDK1-inhibitor treatment, demonstrating a critical role of CDK2 in myogenic cell migration. Overall, our study demonstrates that in myogenic cells, the ERK-CDK2 axis promotes not only G1/S transition but also migration, thus providing a novel mechanism for efficient muscle regeneration.", "classifications": [], "creators": [ { "creator_type": "author", "first_name": "Yumi", "last_name": "Konagaya", "name": null }, { "creator_type": "author", "first_name": "Kanako", "last_name": "Takakura", "name": null }, { "creator_type": "author", "first_name": "Maina", "last_name": "Sogabe", "name": null }, { "creator_type": "author", "first_name": "Anjali", "last_name": "Bisaria", "name": null }, { "creator_type": "author", "first_name": "Chad", "last_name": "Liu", "name": null }, { "creator_type": "author", "first_name": "Tobias", "last_name": "Meyer", "name": null }, { "creator_type": "author", "first_name": "Atsuko", "last_name": "Sehara-Fujisawa", "name": null }, { "creator_type": "author", "first_name": "Michiyuki", "last_name": "Matsuda", "name": null }, { "creator_type": "author", "first_name": "Kenta", "last_name": "Terai", "name": null } ], "identifiers": { "doi": { "normalized": "10.1080/15384101.2020.1838779" }, "pmcid": { "normalized": "PMC7714504" }, "pmid": { "normalized": "33131406" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cardiotoxins", "descriptor_ui": "D054715", "major_topic": false }, { "descriptor": "Cell Cycle", "descriptor_ui": "D002453", "major_topic": false }, { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "Cell Movement", "descriptor_ui": "D002465", "major_topic": false }, { "descriptor": "Cell Proliferation", "descriptor_ui": "D049109", "major_topic": false }, { "descriptor": "Cyclin-Dependent Kinase 2", "descriptor_ui": "D051357", "major_topic": false }, { "descriptor": "Epithelial Cells", "descriptor_ui": "D004847", "major_topic": false }, { "descriptor": "Extracellular Signal-Regulated MAP Kinases", "descriptor_ui": "D048049", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Intravital Microscopy", "descriptor_ui": "D000069416", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "MAP Kinase Signaling System", "descriptor_ui": "D020935", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Transgenic", "descriptor_ui": "D008822", "major_topic": false }, { "descriptor": "Muscle Development", "descriptor_ui": "D024510", "major_topic": false }, { "descriptor": "Muscle Fibers, Skeletal", "descriptor_ui": "D018485", "major_topic": false }, { "descriptor": "Muscle, Skeletal", "descriptor_ui": "D018482", "major_topic": false }, { "descriptor": "Regeneration", "descriptor_ui": "D012038", "major_topic": false }, { "descriptor": "Satellite Cells, Skeletal Muscle", "descriptor_ui": "D032496", "major_topic": false }, { "descriptor": "Transfection", "descriptor_ui": "D014162", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020 Nov", "date_precision": "unknown", "issue": "22", "normalized_date": null, "pages": "3167-3181", "proceedings_title": null, "publisher": "", "title": "Cell cycle (Georgetown, Tex.)", "volume": "19", "year": 2020 }, "ssbd": { "database": [ "ssbd-database-000178" ], "repository": [ "ssbd-repos-000178" ] }, "title": "Intravital imaging reveals cell cycle-dependent myogenic cell migration during muscle regeneration.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Colorectal carcinogenesis in familial adenomatous polyposis (FAP) follows a conventional adenoma-carcinoma sequence. However, previous studies have also reported the occurrence of traditional serrated adenomas (TSAs) in patients with FAP. In the present study, we analyzed the clinicopathologic and molecular features of 37 TSAs from 21 FAP patients. Histologically, the majority of FAP-associated TSAs showed typical cytology and slit-like serration; however, ectopic crypt formation was infrequent. Next-generation sequencing and Sanger sequencing identified KRAS and BRAF V600E mutations in 18 (49%) and 14 (38%) TSAs, respectively. Somatic APC mutations were detected in 26 lesions (84% of analyzed cases). Three lesions had BRAF non-V600E mutations, and 2 of them had a concurrent KRAS mutation. Seven TSAs (19%) were associated with a precursor polyp, 6 with a hyperplastic polyp, and 1 with a sessile serrated lesion, and all of them showed the BRAF V600E mutation. Additional sequencing analysis of 4 TSAs with a precursor polyp showed that the BRAF V600E mutation was shared between the TSA and precursor components, but APC mutations were exclusive to the TSA component in all the analyzed lesions. None of the lesions showed the high CpG island methylation phenotype. These results indicate that FAP-associated TSAs frequently have KRAS or BRAF mutations, similar to sporadic cases, and second-hit somatic APC mutations are commonly involved in their tumorigenesis as in other FAP-associated tumors. Although progression to adenocarcinoma is likely rare, tumorigenesis via the serrated pathway occurs in patients with FAP.", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Takuma", "last_name": "Okamura", "name": null }, { "creator_type": "author", "first_name": "Taiki", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Tomoaki", "last_name": "Naka", "name": null }, { "creator_type": "author", "first_name": "Teruhiko", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Noriko", "last_name": "Tanabe", "name": null }, { "creator_type": "author", "first_name": "Reiko", "last_name": "Ogawa", "name": null }, { "creator_type": "author", "first_name": "Masayoshi", "last_name": "Yamada", "name": null }, { "creator_type": "author", "first_name": "Yutaka", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null }, { "creator_type": "author", "first_name": "Shigeki", "last_name": "Sekine", "name": null } ], "identifiers": { "doi": { "normalized": "10.1097/pas.0000000000001502" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "32384323" } }, "mesh": [ { "descriptor": "Adenomatous Polyposis Coli", "descriptor_ui": "D011125", "major_topic": false }, { "descriptor": "Adolescent", "descriptor_ui": "D000293", "major_topic": false }, { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Biomarkers, Tumor", "descriptor_ui": "D014408", "major_topic": false }, { "descriptor": "Colonic Polyps", "descriptor_ui": "D003111", "major_topic": false }, { "descriptor": "Disease Progression", "descriptor_ui": "D018450", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Genetic Predisposition to Disease", "descriptor_ui": "D020022", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": true }, { "descriptor": "Phenotype", "descriptor_ui": "D010641", "major_topic": false }, { "descriptor": "Proto-Oncogene Proteins B-raf", "descriptor_ui": "D048493", "major_topic": false }, { "descriptor": "Proto-Oncogene Proteins p21(ras)", "descriptor_ui": "D016283", "major_topic": false }, { "descriptor": "Young Adult", "descriptor_ui": "D055815", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020 Sep", "date_precision": "unknown", "issue": "9", "normalized_date": null, "pages": "1282-1289", "proceedings_title": null, "publisher": "", "title": "The American journal of surgical pathology", "volume": "44", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Clinicopathologic and Molecular Characteristics of Familial Adenomatous Polyposis-associated Traditional Serrated Adenoma.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "", "classifications": [ { "id": "Iwaki", "label": "Group Iwaki", "parent": "Toyoshima", "type": "group" }, { "id": "Toyoshima", "label": "Team Toyoshima", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Mitsuhiro", "last_name": "Iwaki", "name": null }, { "creator_type": "author", "first_name": "Yuji", "last_name": "Hara", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/s12551-020-00631-6" }, "pmcid": { "normalized": "PMC7242579" }, "pmid": { "normalized": "32034677" } }, "mesh": [], "publication": { "conference_name": null, "date": "2020 Apr", "date_precision": "unknown", "issue": "2", "normalized_date": null, "pages": "267-268", "proceedings_title": null, "publisher": "", "title": "Biophysical reviews", "volume": "12", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Overview of the frontiers in multi-scale mechanobiology of muscle and vascular system-Session 1SGA.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Pluripotent stem cells are increasingly used to model different aspects of embryogenesis and organ formation(1). Despite recent advances in in vitro induction of major mesodermal lineages and cell types(2,3), experimental model systems that can recapitulate more complex features of human mesoderm development and patterning are largely missing. Here we used induced pluripotent stem cells for the stepwise in vitro induction of presomitic mesoderm and its derivatives to model distinct aspects of human somitogenesis. We focused initially on modelling the human segmentation clock, a major biological concept believed to underlie the rhythmic and controlled emergence of somites, which give rise to the segmental pattern of the vertebrate axial skeleton. We observed oscillatory expression of core segmentation clock genes, including HES7 and DKK1, determined the period of the human segmentation clock to be around five hours, and demonstrated the presence of dynamic travelling-wave-like gene expression in in vitro-induced human presomitic mesoderm. Furthermore, we identified and compared oscillatory genes in human and mouse presomitic mesoderm derived from pluripotent stem cells, which revealed species-specific and shared molecular components and pathways associated with the putative mouse and human segmentation clocks. Using CRISPR-Cas9-based genome editing technology, we then targeted genes for which mutations in patients with segmentation defects of the vertebrae, such as spondylocostal dysostosis, have been reported (HES7, LFNG, DLL3 and MESP2). Subsequent analysis of patient-like and patient-derived induced pluripotent stem cells revealed gene-specific alterations in oscillation, synchronization or differentiation properties. Our findings provide insights into the human segmentation clock as well as diseases associated with human axial skeletogenesis.", "classifications": [ { "id": "Yamamoto", "label": "Group Yamamoto", "parent": "Toyoshima", "type": "group" }, { "id": "Toyoshima", "label": "Team Toyoshima", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Mitsuhiro", "last_name": "Matsuda", "name": null }, { "creator_type": "author", "first_name": "Yoshihiro", "last_name": "Yamanaka", "name": null }, { "creator_type": "author", "first_name": "Maya", "last_name": "Uemura", "name": null }, { "creator_type": "author", "first_name": "Mitsujiro", "last_name": "Osawa", "name": null }, { "creator_type": "author", "first_name": "Megumu K.", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Ayako", "last_name": "Nagahashi", "name": null }, { "creator_type": "author", "first_name": "Megumi", "last_name": "Nishio", "name": null }, { "creator_type": "author", "first_name": "Long", "last_name": "Guo", "name": null }, { "creator_type": "author", "first_name": "Shiro", "last_name": "Ikegawa", "name": null }, { "creator_type": "author", "first_name": "Satoko", "last_name": "Sakurai", "name": null }, { "creator_type": "author", "first_name": "Shunsuke", "last_name": "Kihara", "name": null }, { "creator_type": "author", "first_name": "Thomas L.", "last_name": "Maurissen", "name": null }, { "creator_type": "author", "first_name": "Michiko", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Tomoko", "last_name": "Matsumoto", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Yoshitomi", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Ikeya", "name": null }, { "creator_type": "author", "first_name": "Noriaki", "last_name": "Kawakami", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Knut", "last_name": "Woltjen", "name": null }, { "creator_type": "author", "first_name": "Miki", "last_name": "Ebisuya", "name": null }, { "creator_type": "author", "first_name": "Junya", "last_name": "Toguchida", "name": null }, { "creator_type": "author", "first_name": "Cantas", "last_name": "Alev", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41586-020-2144-9" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "32238941" } }, "mesh": [ { "descriptor": "Abnormalities, Multiple", "descriptor_ui": "D000015", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Basic Helix-Loop-Helix Proteins", "descriptor_ui": "D051792", "major_topic": false }, { "descriptor": "Biological Clocks", "descriptor_ui": "D001683", "major_topic": false }, { "descriptor": "Embryonic Development", "descriptor_ui": "D047108", "major_topic": false }, { "descriptor": "Gene Editing", "descriptor_ui": "D000072669", "major_topic": false }, { "descriptor": "Gene Expression Regulation, Developmental", "descriptor_ui": "D018507", "major_topic": false }, { "descriptor": "Glycosyltransferases", "descriptor_ui": "D016695", "major_topic": false }, { "descriptor": "Hernia, Diaphragmatic", "descriptor_ui": "D006548", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "In Vitro Techniques", "descriptor_ui": "D066298", "major_topic": false }, { "descriptor": "Intercellular Signaling Peptides and Proteins", "descriptor_ui": "D036341", "major_topic": false }, { "descriptor": "Intracellular Signaling Peptides and Proteins", "descriptor_ui": "D047908", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Membrane Proteins", "descriptor_ui": "D008565", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Phenotype", "descriptor_ui": "D010641", "major_topic": false }, { "descriptor": "Pluripotent Stem Cells", "descriptor_ui": "D039904", "major_topic": false }, { "descriptor": "Somites", "descriptor_ui": "D019170", "major_topic": false }, { "descriptor": "Time Factors", "descriptor_ui": "D013997", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020 Apr", "date_precision": "unknown", "issue": "7801", "normalized_date": null, "pages": "124-129", "proceedings_title": null, "publisher": "", "title": "Nature", "volume": "580", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Recapitulating the human segmentation clock with pluripotent stem cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: 5-aminolevulinic acid (5-ALA) has been utilized for cancer diagnosis as a fluorescence probe. We have reported the feasibility of 5-ALA-induced protoporphyrin IX (PpIX) fluorescence for detecting lymph node (LN) metastasis in gastrointestinal malignancies. However, a major barrier to the fluorescence diagnosis has been that the evaluation has been highly dependent on the observers. In this study, we examined the validity of a developed device for automated detection without subjectivity. METHODS: Gastric cancer patients who received oral administration of 5-ALA (20 mg/kg) prior to surgery were enrolled. For a total of 323 LNs obtained from 64 patients, the diagnostic results of the device were compared to those of conventional histopathological examination based on hematoxylin-and-eosin-stained slides. The accuracy with the device was compared to that of stereoscopic detection with conventional fluorescence microscopy for 211 LNs from 42 patients. We used two types of image processing that we previously developed to eliminate autofluorescence of background tissues: differential and ratio methods. RESULTS: For detection of metastasis in 323 LNs, the areas under the receiver operating characteristic curves with the differential method and ratio method were 0.921 and 0.909, respectively. The sensitivity, specificity, and accuracy with the differential method were 78.0%, 96.8%, and 94.4%; while those with the ratio method were 78.0%, 96.1%, and 93.8%, respectively. In 211 LN analysis, the diagnostic accuracy with the device was comparable to that of stereoscopic examination. CONCLUSION: Our device for automated detection of LN metastasis using 5-ALA can be a useful tool for intraoperative diagnosis.", "classifications": [ { "id": "Tanaka", "label": "Group Tanaka", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Matsumoto", "name": null }, { "creator_type": "author", "first_name": "Yasutoshi", "last_name": "Murayama", "name": null }, { "creator_type": "author", "first_name": "Hisataka", "last_name": "Matsuo", "name": null }, { "creator_type": "author", "first_name": "Kengo", "last_name": "Okochi", "name": null }, { "creator_type": "author", "first_name": "Naotaka", "last_name": "Koshiishi", "name": null }, { "creator_type": "author", "first_name": "Yoshinori", "last_name": "Harada", "name": null }, { "creator_type": "author", "first_name": "Hideo", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Tetsuro", "last_name": "Takamatsu", "name": null }, { "creator_type": "author", "first_name": "Eigo", "last_name": "Otsuji", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/s10120-020-01044-w" }, "pmcid": { "normalized": "PMC7305096" }, "pmid": { "normalized": "32048096" } }, "mesh": [ { "descriptor": "Adenocarcinoma", "descriptor_ui": "D000230", "major_topic": false }, { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Aged, 80 and over", "descriptor_ui": "D000369", "major_topic": false }, { "descriptor": "Aminolevulinic Acid", "descriptor_ui": "D000622", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Fluorescent Dyes", "descriptor_ui": "D005456", "major_topic": false }, { "descriptor": "Follow-Up Studies", "descriptor_ui": "D005500", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Image Processing, Computer-Assisted", "descriptor_ui": "D007091", "major_topic": false }, { "descriptor": "Lymph Nodes", "descriptor_ui": "D008198", "major_topic": false }, { "descriptor": "Lymphatic Metastasis", "descriptor_ui": "D008207", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Photosensitizing Agents", "descriptor_ui": "D017319", "major_topic": false }, { "descriptor": "Prognosis", "descriptor_ui": "D011379", "major_topic": false }, { "descriptor": "Protoporphyrins", "descriptor_ui": "D011524", "major_topic": false }, { "descriptor": "Retrospective Studies", "descriptor_ui": "D012189", "major_topic": false }, { "descriptor": "Stomach Neoplasms", "descriptor_ui": "D013274", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020 Jul", "date_precision": "unknown", "issue": "4", "normalized_date": null, "pages": "725-733", "proceedings_title": null, "publisher": "", "title": "Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association", "volume": "23", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "5-ALA-assistant automated detection of lymph node metastasis in gastric cancer patients.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.jtho.2020.10.011" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "33246595" } }, "mesh": [ { "descriptor": "Basic Helix-Loop-Helix Proteins", "descriptor_ui": "D051792", "major_topic": false }, { "descriptor": "Carcinoma, Small Cell", "descriptor_ui": "D018288", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Lung Neoplasms", "descriptor_ui": "D008175", "major_topic": true }, { "descriptor": "Octamer Transcription Factors", "descriptor_ui": "D050810", "major_topic": false }, { "descriptor": "Small Cell Lung Carcinoma", "descriptor_ui": "D055752", "major_topic": true } ], "publication": { "conference_name": null, "date": "2020 Dec", "date_precision": "unknown", "issue": "12", "normalized_date": null, "pages": "1819-1822", "proceedings_title": null, "publisher": "", "title": "Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer", "volume": "15", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Reassessing the SCLC Subtypes.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: Primary tumor location is a critical prognostic factor that also impacts the efficacy of anti-epidermal growth factor receptor (EGFR) therapy in wild-type RAS (KRAS/NRAS) metastatic colorectal cancer (CRC). However, the association between the incidence of BRAF and phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) mutations and primary tumor location remains unclear. METHODS: We prospectively collected tumor samples and clinical data of patients from 15 hospitals between August 2014 and April 2016 to investigate RAS, BRAF, and PIK3CA mutations using a polymerase chain reaction-based assay. According to the primary tumor location, patients were classified to right-sided (from cecum to splenic flexure) and left-sided (from descending colon to rectum) tumor groups. RESULTS: In total, 577 patients with CRC were investigated, 331 patients (57%) had CRC with wild-type RAS; of these 331 patients, 10.5%, 4.8%, and 5.9% patients harbored BRAF(V600E), BRAF(non-V600E), and PIK3CA mutations, respectively. BRAF/PIK3CA mutations were more frequent in females, patients with right-sided tumors, and patients with peritoneal metastasis cases and less frequent in patients with liver metastases. The prevalence rates of BRAF(V600E) and PIK3CA mutations were higher in patients with right-sided tumors than in those with left-sided tumors (32.3% vs. 4.8% and 17.2% vs. 3.6%, respectively). CONCLUSIONS: More than half of the patients with right-sided CRC and wild-type RAS harbored BRAF/PIK3CA mutations, including BRAF(non-V600E), which may contribute to the difference in the anti-EGFR efficacy between the right- and left-sided CRC.", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Hiroya", "last_name": "Taniguchi", "name": null }, { "creator_type": "author", "first_name": "Keisuke", "last_name": "Uehara", "name": null }, { "creator_type": "author", "first_name": "Goro", "last_name": "Nakayama", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Nakayama", "name": null }, { "creator_type": "author", "first_name": "Toshisada", "last_name": "Aiba", "name": null }, { "creator_type": "author", "first_name": "Norifumi", "last_name": "Hattori", "name": null }, { "creator_type": "author", "first_name": "Masato", "last_name": "Kataoka", "name": null }, { "creator_type": "author", "first_name": "Yasuyuki", "last_name": "Nakano", "name": null }, { "creator_type": "author", "first_name": "Yoshihisa", "last_name": "Kawase", "name": null }, { "creator_type": "author", "first_name": "Osamu", "last_name": "Okochi", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Matsuoka", "name": null }, { "creator_type": "author", "first_name": "Setsuo", "last_name": "Utsunomiya", "name": null }, { "creator_type": "author", "first_name": "Eiji", "last_name": "Sakamoto", "name": null }, { "creator_type": "author", "first_name": "Yoshinori", "last_name": "Mori", "name": null }, { "creator_type": "author", "first_name": "Shinichi", "last_name": "Umeda", "name": null }, { "creator_type": "author", "first_name": "Toshio", "last_name": "Shikano", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Komori", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Tajika", "name": null }, { "creator_type": "author", "first_name": "Shigenori", "last_name": "Kadowaki", "name": null }, { "creator_type": "author", "first_name": "Kei", "last_name": "Muro", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.tranon.2020.100786" }, "pmcid": { "normalized": "PMC7232108" }, "pmid": { "normalized": "32428838" } }, "mesh": [], "publication": { "conference_name": null, "date": "2020 Jul", "date_precision": "unknown", "issue": "7", "normalized_date": null, "pages": "100786", "proceedings_title": null, "publisher": "", "title": "Translational oncology", "volume": "13", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Tumor Location Is Associated With the Prevalence of Braf And Pik3ca Mutations in Patients with Wild-Type Ras Colorectal Cancer: A Prospective Multi-Center Cohort Study in Japan.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Squamous cell papilloma (SCP) is a benign neoplasm of the head and neck. Human papillomavirus (HPV) has been reported to be a tumourigenic factor for SCP. However, not all SCPs are positive for HPV, suggesting that other possible mechanisms are involved in their development. In this study, we examined the mutational status of 51 SCPs using targeted panel sequencing in addition to HPV status using GP5+/GP6+ PCR. HPV DNA was detected in 6 (12%) SCPs, while KRAS and HRAS mutations were detected in 18 (35%) and 17 (33%) SCPs, respectively. Notably, KRAS mutations, HRAS mutations and HPV infection were mutually exclusive. The larynx and trachea (4/7, 57%) were more preferentially infected by HPV than the other sites (2/44, 5%, p = 0.0019) and HPV was associated with multifocal development (4/5, 80%). In contrast, KRAS and HRAS mutations in SCPs were evenly distributed across the anatomical sites and found only in single SCPs. In conclusion, this study demonstrated that HPV was not frequently involved in SCPs and that RAS mutations were more common alterations. In contrast to inverted sinonasal papillomas and oncocytic sinonasal papillomas, SCP may not be a precursor lesion of carcinoma, because these aetiological events in SCP are distinct from squamous cell carcinoma in the same sites.", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Eiichi", "last_name": "Sasaki", "name": null }, { "creator_type": "author", "first_name": "Katsuhiro", "last_name": "Masago", "name": null }, { "creator_type": "author", "first_name": "Shiro", "last_name": "Fujita", "name": null }, { "creator_type": "author", "first_name": "Nobuhiro", "last_name": "Hanai", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/cjp2.157" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "31960612" } }, "mesh": [ { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Aged, 80 and over", "descriptor_ui": "D000369", "major_topic": false }, { "descriptor": "Alphapapillomavirus", "descriptor_ui": "D052685", "major_topic": false }, { "descriptor": "Carcinoma, Squamous Cell", "descriptor_ui": "D002294", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": false }, { "descriptor": "Neck", "descriptor_ui": "D009333", "major_topic": false }, { "descriptor": "Nose Neoplasms", "descriptor_ui": "D009669", "major_topic": false }, { "descriptor": "Papilloma, Inverted", "descriptor_ui": "D018308", "major_topic": false }, { "descriptor": "Papillomavirus Infections", "descriptor_ui": "D030361", "major_topic": false }, { "descriptor": "Paranasal Sinus Neoplasms", "descriptor_ui": "D010255", "major_topic": false }, { "descriptor": "Proto-Oncogene Proteins p21(ras)", "descriptor_ui": "D016283", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020 Apr", "date_precision": "unknown", "issue": "2", "normalized_date": null, "pages": "154-159", "proceedings_title": null, "publisher": "", "title": "The Journal of Pathology: Clinical Research", "volume": "6", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Frequent KRAS and HRAS mutations in squamous cell papillomas of the head and neck.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Using genome-wide clustered regularly interspaced short palindromic repeats (CRISPR) screens to understand endocrine drug resistance, we discovered ARID1A and other SWI/SNF complex components as the factors most critically required for response to two classes of estrogen receptor-alpha (ER) antagonists. In this context, SWI/SNF-specific gene deletion resulted in drug resistance. Unexpectedly, ARID1A was also the top candidate in regard to response to the bromodomain and extraterminal domain inhibitor JQ1, but in the opposite direction, with loss of ARID1A sensitizing breast cancer cells to bromodomain and extraterminal domain inhibition. We show that ARID1A is a repressor that binds chromatin at ER cis-regulatory elements. However, ARID1A elicits repressive activity in an enhancer-specific, but forkhead box A1-dependent and active, ER-independent manner. Deletion of ARID1A resulted in loss of histone deacetylase 1 binding, increased histone 4 lysine acetylation and subsequent BRD4-driven transcription and growth. ARID1A mutations are more frequent in treatment-resistant disease, and our findings provide mechanistic insight into this process while revealing rational treatment strategies for these patients.", "classifications": [ { "id": "Yusa", "label": "Group Yusa", "parent": "Eiraku", "type": "group" }, { "id": "Eiraku", "label": "Team Eiraku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Sankari", "last_name": "Nagarajan", "name": null }, { "creator_type": "author", "first_name": "Shalini V.", "last_name": "Rao", "name": null }, { "creator_type": "author", "first_name": "Joseph", "last_name": "Sutton", "name": null }, { "creator_type": "author", "first_name": "Danya", "last_name": "Cheeseman", "name": null }, { "creator_type": "author", "first_name": "Shanade", "last_name": "Dunn", "name": null }, { "creator_type": "author", "first_name": "Evangelia K.", "last_name": "Papachristou", "name": null }, { "creator_type": "author", "first_name": "Jose-Enrique Gonzalez", "last_name": "Prada", "name": null }, { "creator_type": "author", "first_name": "Dominique-Laurent", "last_name": "Couturier", "name": null }, { "creator_type": "author", "first_name": "Sanjeev", "last_name": "Kumar", "name": null }, { "creator_type": "author", "first_name": "Kamal", "last_name": "Kishore", "name": null }, { "creator_type": "author", "first_name": "Chandra Sekhar Reddy", "last_name": "Chilamakuri", "name": null }, { "creator_type": "author", "first_name": "Silvia-Elena", "last_name": "Glont", "name": null }, { "creator_type": "author", "first_name": "Emily", "last_name": "Archer Goode", "name": null }, { "creator_type": "author", "first_name": "Cara", "last_name": "Brodie", "name": null }, { "creator_type": "author", "first_name": "Naomi", "last_name": "Guppy", "name": null }, { "creator_type": "author", "first_name": "Rachael", "last_name": "Natrajan", "name": null }, { "creator_type": "author", "first_name": "Alejandra", "last_name": "Bruna", "name": null }, { "creator_type": "author", "first_name": "Carlos", "last_name": "Caldas", "name": null }, { "creator_type": "author", "first_name": "Alasdair", "last_name": "Russell", "name": null }, { "creator_type": "author", "first_name": "Rasmus", "last_name": "Siersbaek", "name": null }, { "creator_type": "author", "first_name": "Kosuke", "last_name": "Yusa", "name": null }, { "creator_type": "author", "first_name": "Igor", "last_name": "Chernukhin", "name": null }, { "creator_type": "author", "first_name": "Jason S.", "last_name": "Carroll", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41588-019-0541-5" }, "pmcid": { "normalized": "PMC7116647" }, "pmid": { "normalized": "31913353" } }, "mesh": [ { "descriptor": "Acetylation", "descriptor_ui": "D000107", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Breast Neoplasms", "descriptor_ui": "D001943", "major_topic": false }, { "descriptor": "Bromodomain Containing Proteins", "descriptor_ui": "D000092468", "major_topic": false }, { "descriptor": "Cell Cycle Proteins", "descriptor_ui": "D018797", "major_topic": false }, { "descriptor": "Cell Proliferation", "descriptor_ui": "D049109", "major_topic": false }, { "descriptor": "Clustered Regularly Interspaced Short Palindromic Repeats", "descriptor_ui": "D064112", "major_topic": false }, { "descriptor": "DNA-Binding Proteins", "descriptor_ui": "D004268", "major_topic": false }, { "descriptor": "Drug Resistance, Neoplasm", "descriptor_ui": "D019008", "major_topic": false }, { "descriptor": "Estrogen Receptor alpha", "descriptor_ui": "D047628", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Gene Expression Regulation, Neoplastic", "descriptor_ui": "D015972", "major_topic": false }, { "descriptor": "Hepatocyte Nuclear Factor 3-alpha", "descriptor_ui": "D051541", "major_topic": false }, { "descriptor": "Histone Deacetylase 1", "descriptor_ui": "D056284", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "MCF-7 Cells", "descriptor_ui": "D061986", "major_topic": false }, { "descriptor": "Mice, Inbred NOD", "descriptor_ui": "D016688", "major_topic": false }, { "descriptor": "Transcription Factors", "descriptor_ui": "D014157", "major_topic": false }, { "descriptor": "Xenograft Model Antitumor Assays", "descriptor_ui": "D023041", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020 Feb", "date_precision": "unknown", "issue": "2", "normalized_date": null, "pages": "187-197", "proceedings_title": null, "publisher": "", "title": "Nature genetics", "volume": "52", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "ARID1A influences HDAC1/BRD4 activity, intrinsic proliferative capacity and breast cancer treatment response.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Missense mutations of the RET gene have been identified in both multiple endocrine neoplasia (MEN) type 2A/B and Hirschsprung disease (HSCR: congenital absence of the enteric nervous system, ENS). Current consensus holds that MEN2A/B and HSCR are caused by activating and inactivating RET mutations, respectively. However, the biological significance of RET missense mutations in vivo has not been fully elucidated. In the present study, we introduced one MEN2B-associated (M918T) and two HSCR-associated (N394K and Y791F) RET missense mutations into the corresponding regions of the mouse Ret gene by genome editing (Ret(M919T) , Ret(N396K) and Ret(Y792F) ) and performed histological examinations of Ret-expressing tissues to understand the pathogenetic impact of each mutant in vivo. Ret(M919T/+) mice displayed MEN2B-related phenotypes, including C-cell hyperplasia and abnormal enlargement of the primary sympathetic ganglia. Similar sympathetic phenotype was observed in Ret(M919T/-) mice, demonstrating a strong pathogenetic effect of the Ret M918T by a single-allele expression. In contrast, no abnormality was found in the ENS of mice harboring the Ret N394K or Y791F mutation. Most surprisingly, single-allele expression of RET N394K or Y791F was sufficient for normal ENS development, indicating that these RET mutants exert largely physiological function in vivo. This study reveals contrasting pathogenetic effects between MEN2B- and HSCR-associated RET missense mutations, and suggests that some of HSCR-associated RET missense mutations are by themselves neither inactivating nor pathogenetic and require involvement of other gene mutations for disease expressivity.", "classifications": [ { "id": "Enomoto", "label": "Group Enomoto", "parent": "Enomoto", "type": "group" }, { "id": "Enomoto", "label": "Team Enomoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Taichi", "last_name": "Nakatani", "name": null }, { "creator_type": "author", "first_name": "Mitsuhiro", "last_name": "Iwasaki", "name": null }, { "creator_type": "author", "first_name": "Atsuhiro", "last_name": "Yamamichi", "name": null }, { "creator_type": "author", "first_name": "Yuta", "last_name": "Yoshioka", "name": null }, { "creator_type": "author", "first_name": "Toshihiro", "last_name": "Uesaka", "name": null }, { "creator_type": "author", "first_name": "Yuko", "last_name": "Bitoh", "name": null }, { "creator_type": "author", "first_name": "Kosaku", "last_name": "Maeda", "name": null }, { "creator_type": "author", "first_name": "Takumi", "last_name": "Fukumoto", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Takemoto", "name": null }, { "creator_type": "author", "first_name": "Hideki", "last_name": "Enomoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/dgd.12664" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "32275061" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Hirschsprung Disease", "descriptor_ui": "D006627", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Inbred ICR", "descriptor_ui": "D008813", "major_topic": false }, { "descriptor": "Multiple Endocrine Neoplasia Type 2b", "descriptor_ui": "D018814", "major_topic": false }, { "descriptor": "Mutation, Missense", "descriptor_ui": "D020125", "major_topic": true }, { "descriptor": "Point Mutation", "descriptor_ui": "D017354", "major_topic": true }, { "descriptor": "Proto-Oncogene Proteins c-ret", "descriptor_ui": "D051096", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020 May", "date_precision": "unknown", "issue": "4", "normalized_date": null, "pages": "214-222", "proceedings_title": null, "publisher": "", "title": "Development, growth & differentiation", "volume": "62", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Point mutagenesis in mouse reveals contrasting pathogenetic effects between MEN2B- and Hirschsprung disease-associated missense mutations of the RET gene.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Steroid hormones are crucial regulators of life-stage transitions during development in animals. However, the molecular mechanisms by which developmental transition through these stages is coupled with optimal metabolic homeostasis remains poorly understood. Here, we demonstrate through mathematical modelling and experimental validation that ecdysteroid-induced metabolic remodelling from resource consumption to conservation can be a successful life-history strategy to maximize fitness in Drosophila larvae in a fluctuating environment. Specifically, the ecdysteroid-inducible protein ImpL2 protects against hydrolysis of circulating trehalose following pupal commitment in larvae. Stored glycogen and triglycerides in the fat body are also conserved, even under fasting conditions. Moreover, pupal commitment dictates reduced energy expenditure upon starvation to maintain available resources, thus negotiating trade-offs in resource allocation at the physiological and behavioural levels. The optimal stage-specific metabolic shift elucidated by our predictive and empirical approaches reveals that Drosophila has developed a highly controlled system for ensuring robust development that may be conserved among higher-order organisms in response to intrinsic and extrinsic cues.", "classifications": [ { "id": "Morishita", "label": "Group Morishita", "parent": "Morishita", "type": "group" }, { "id": "Morishita", "label": "Team Morishita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Takayuki", "last_name": "Yamada", "name": null }, { "creator_type": "author", "first_name": "Ken-Ichi", "last_name": "Hironaka", "name": null }, { "creator_type": "author", "first_name": "Okiko", "last_name": "Habara", "name": null }, { "creator_type": "author", "first_name": "Yoshihiro", "last_name": "Morishita", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Nishimura", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s42255-020-00293-4" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "33046910" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Behavior, Animal", "descriptor_ui": "D001522", "major_topic": false }, { "descriptor": "Body Size", "descriptor_ui": "D049628", "major_topic": false }, { "descriptor": "Drosophila", "descriptor_ui": "D004330", "major_topic": false }, { "descriptor": "Drosophila Proteins", "descriptor_ui": "D029721", "major_topic": false }, { "descriptor": "Eating", "descriptor_ui": "D004435", "major_topic": false }, { "descriptor": "Ecdysteroids", "descriptor_ui": "D026461", "major_topic": false }, { "descriptor": "Glycogen", "descriptor_ui": "D006003", "major_topic": false }, { "descriptor": "Insulin-Like Growth Factor Binding Proteins", "descriptor_ui": "D018969", "major_topic": false }, { "descriptor": "Larva", "descriptor_ui": "D007814", "major_topic": false }, { "descriptor": "Life History Traits", "descriptor_ui": "D000071421", "major_topic": false }, { "descriptor": "Lipid Metabolism", "descriptor_ui": "D050356", "major_topic": false }, { "descriptor": "Metabolomics", "descriptor_ui": "D055432", "major_topic": false }, { "descriptor": "Models, Theoretical", "descriptor_ui": "D008962", "major_topic": false }, { "descriptor": "Pupa", "descriptor_ui": "D011679", "major_topic": false }, { "descriptor": "Starvation", "descriptor_ui": "D013217", "major_topic": false }, { "descriptor": "Triglycerides", "descriptor_ui": "D014280", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020 Oct", "date_precision": "unknown", "issue": "10", "normalized_date": null, "pages": "1096-1112", "proceedings_title": null, "publisher": "", "title": "Nature metabolism", "volume": "2", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "A developmental checkpoint directs metabolic remodelling as a strategy against starvation in Drosophila.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Kinesin is a motor protein that plays important roles in a variety of cellular functions. In vivo, multiple kinesin molecules are bound to cargo and work as a team to produce larger forces or higher speeds than a single kinesin. However, the coordination of kinesins remains poorly understood because of the experimental difficulty in controlling the number and arrangement of kinesins, which are considered to affect their coordination. Here, we report that both the number and spacing significantly influence the velocity of microtubules driven by nonprocessive kinesin-14 (Ncd), whereas neither the number nor the spacing changes the velocity in the case of highly processive kinesin-1. This result was realized by the optimum nanopatterning method of kinesins that enables immobilization of a single kinesin on a nanopillar. Our proposed method enables us to study the individual effects of the number and spacing of motors on the collective dynamics of multiple motors.", "classifications": [ { "id": "Shintaku", "label": "Group Shintaku", "parent": "Shintaku", "type": "group" }, { "id": "Shintaku", "label": "Team Shintaku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Taikopaul", "last_name": "Kaneko", "name": null }, { "creator_type": "author", "first_name": "Ken'ya", "last_name": "Furuta", "name": null }, { "creator_type": "author", "first_name": "Kazuhiro", "last_name": "Oiwa", "name": null }, { "creator_type": "author", "first_name": "Hirofumi", "last_name": "Shintaku", "name": null }, { "creator_type": "author", "first_name": "Hidetoshi", "last_name": "Kotera", "name": null }, { "creator_type": "author", "first_name": "Ryuji", "last_name": "Yokokawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1126/sciadv.aax7413" }, "pmcid": { "normalized": "PMC6976292" }, "pmid": { "normalized": "32010782" } }, "mesh": [ { "descriptor": "Gold", "descriptor_ui": "D006046", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Kinesins", "descriptor_ui": "D016547", "major_topic": false }, { "descriptor": "Kinetics", "descriptor_ui": "D007700", "major_topic": false }, { "descriptor": "Microtubules", "descriptor_ui": "D008870", "major_topic": false }, { "descriptor": "Molecular Imaging", "descriptor_ui": "D057054", "major_topic": false }, { "descriptor": "Molecular Motor Proteins", "descriptor_ui": "D020409", "major_topic": false }, { "descriptor": "Nanofibers", "descriptor_ui": "D057139", "major_topic": false }, { "descriptor": "Spectrum Analysis", "descriptor_ui": "D013057", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020 Jan", "date_precision": "unknown", "issue": "4", "normalized_date": null, "pages": "eaax7413", "proceedings_title": null, "publisher": "", "title": "Science advances", "volume": "6", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Different motilities of microtubules driven by kinesin-1 and kinesin-14 motors patterned on nanopillars.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Biomarker testing is recognized as being indispensable for selecting patients with advanced lung cancer. EGFR mutation is the first biomarker for therapeutic selection of lung cancer patients since the identification of the correlation between EGFR TKI response and EGFR mutation status. The biomarker testing in Japan mostly follows those corresponding to the US. However, there are some differences due to the national health care program and the medical environment. In this review, we introduce the history and current status of the biomarker testing for lung cancer in Japan and discuss perspectives, focusing on cell-free DNA (cfDNA)-based panel testing.", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Noriko", "last_name": "Motoi", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null } ], "identifiers": { "doi": { "normalized": "10.21037/tlcr.2020.03.09" }, "pmcid": { "normalized": "PMC7354153" }, "pmid": { "normalized": "32676353" } }, "mesh": [], "publication": { "conference_name": null, "date": "2020 Jun", "date_precision": "unknown", "issue": "3", "normalized_date": null, "pages": "879-886", "proceedings_title": null, "publisher": "", "title": "Translational lung cancer research", "volume": "9", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Lung cancer biomarker tests: the history and perspective in Japan.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Two-photon excitation microscopy is one of the key techniques used to observe three-dimensional (3-D) structures in biological samples. We utilized a visible-wavelength laser beam for two-photon excitation in a multifocus confocal scanning system to improve the spatial resolution and image contrast in 3-D live-cell imaging. Experimental and numerical analyses revealed that the axial resolution has improved for a wide range of pinhole sizes used for confocal detection. We observed the 3-D movements of the Golgi bodies in living HeLa cells with an imaging speed of 2 s per volume. We also confirmed that the time-lapse observation up to 8 min did not cause significant cell damage in two-photon excitation experiments using wavelengths in the visible light range. These results demonstrate that multifocus, two-photon excitation microscopy with the use of a visible wavelength can constitute a simple technique for 3-D visualization of living cells with high spatial resolution and image contrast.", "classifications": [ { "id": "Fujita", "label": "Group Fujita", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Ryosuke", "last_name": "Oketani", "name": null }, { "creator_type": "author", "first_name": "Haruka", "last_name": "Suda", "name": null }, { "creator_type": "author", "first_name": "Kumiko", "last_name": "Uegaki", "name": null }, { "creator_type": "author", "first_name": "Toshiki", "last_name": "Kubo", "name": null }, { "creator_type": "author", "first_name": "Tomoki", "last_name": "Matsuda", "name": null }, { "creator_type": "author", "first_name": "Masahito", "last_name": "Yamanaka", "name": null }, { "creator_type": "author", "first_name": "Yoshiyuki", "last_name": "Arai", "name": null }, { "creator_type": "author", "first_name": "Nicholas I.", "last_name": "Smith", "name": null }, { "creator_type": "author", "first_name": "Takeharu", "last_name": "Nagai", "name": null }, { "creator_type": "author", "first_name": "Katsumasa", "last_name": "Fujita", "name": null } ], "identifiers": { "doi": { "normalized": "10.1117/1.jbo.25.1.014502" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "31691550" } }, "mesh": [ { "descriptor": "Fluorescent Dyes", "descriptor_ui": "D005456", "major_topic": false }, { "descriptor": "Golgi Apparatus", "descriptor_ui": "D006056", "major_topic": false }, { "descriptor": "HeLa Cells", "descriptor_ui": "D006367", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Imaging, Three-Dimensional", "descriptor_ui": "D021621", "major_topic": false }, { "descriptor": "Microscopy, Fluorescence, Multiphoton", "descriptor_ui": "D036641", "major_topic": false }, { "descriptor": "Movement", "descriptor_ui": "D009068", "major_topic": false }, { "descriptor": "Optical Phenomena", "descriptor_ui": "D055620", "major_topic": false }, { "descriptor": "Single-Cell Analysis", "descriptor_ui": "D059010", "major_topic": false }, { "descriptor": "Time-Lapse Imaging", "descriptor_ui": "D059008", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020 Jan", "date_precision": "unknown", "issue": "1", "normalized_date": null, "pages": "", "proceedings_title": null, "publisher": "", "title": "Journal of Biomedical Optics", "volume": "25", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Visible-wavelength two-photon excitation microscopy with multifocus scanning for volumetric live-cell imaging.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: Novel therapeutic agents have improved survival outcomes in patients with advanced solid tumors. In parallel, the development of predictive biomarkers to identify patients who are likely to benefit from a certain treatment has also contributed to the improvement of survival. Recently, clinical trials have reported the efficacy of immune checkpoint inhibitors in the treatment of mismatch repair-deficient (dMMR) advanced solid tumors. In Japan, a PD-1 inhibitor for dMMR advanced solid tumors, regardless of the primary tumor site, has been approved. However, there are some issues related to administering immune checkpoint inhibitors in the clinical practice setting, making it necessary to develop the guidelines. METHODS: Clinical questions (CQs) regarding medical care were formulated for patients with dMMR advanced solid tumors, and evidence to the CQs was collected by manual search to prepare recommendations. Then, the committee members voted to determine the level of each recommendation considering the strength of evidence, expected risks and benefits to patients, and other factors. RESULTS: The current guideline, which we consider a provisional clinical opinion at this point, describes the 11 requirements to be considered in terms of patients for whom dMMR testing is recommended, the timing and methods of dMMR testing, and clinical care systems required to perform dMMR testing properly and to administer immune checkpoint inhibitors safely. CONCLUSION: This provisional clinical opinion proposes the requirements for performing dMMR testing properly to select patients who are likely to benefit from immune checkpoint inhibitors and administering them safely.", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Saori", "last_name": "Mishima", "name": null }, { "creator_type": "author", "first_name": "Hiroya", "last_name": "Taniguchi", "name": null }, { "creator_type": "author", "first_name": "Kiwamu", "last_name": "Akagi", "name": null }, { "creator_type": "author", "first_name": "Eishi", "last_name": "Baba", "name": null }, { "creator_type": "author", "first_name": "Yutaka", "last_name": "Fujiwara", "name": null }, { "creator_type": "author", "first_name": "Akira", "last_name": "Hirasawa", "name": null }, { "creator_type": "author", "first_name": "Masafumi", "last_name": "Ikeda", "name": null }, { "creator_type": "author", "first_name": "Osamu", "last_name": "Maeda", "name": null }, { "creator_type": "author", "first_name": "Kei", "last_name": "Muro", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Nishihara", "name": null }, { "creator_type": "author", "first_name": "Hiroyki", "last_name": "Nishiyama", "name": null }, { "creator_type": "author", "first_name": "Tadao", "last_name": "Takano", "name": null }, { "creator_type": "author", "first_name": "Katsuya", "last_name": "Tsuchihara", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null }, { "creator_type": "author", "first_name": "Yasuhiro", "last_name": "Kodera", "name": null }, { "creator_type": "author", "first_name": "Takayuki", "last_name": "Yoshino", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/s10147-019-01498-8" }, "pmcid": { "normalized": "PMC6989445" }, "pmid": { "normalized": "31286289" } }, "mesh": [ { "descriptor": "Antineoplastic Agents, Immunological", "descriptor_ui": "D000074322", "major_topic": false }, { "descriptor": "B7-H1 Antigen", "descriptor_ui": "D060890", "major_topic": false }, { "descriptor": "Colorectal Neoplasms, Hereditary Nonpolyposis", "descriptor_ui": "D003123", "major_topic": false }, { "descriptor": "DNA Mismatch Repair", "descriptor_ui": "D053843", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Immunotherapy", "descriptor_ui": "D007167", "major_topic": false }, { "descriptor": "Japan", "descriptor_ui": "D007564", "major_topic": false }, { "descriptor": "Medical Oncology", "descriptor_ui": "D008495", "major_topic": false }, { "descriptor": "Molecular Targeted Therapy", "descriptor_ui": "D058990", "major_topic": false }, { "descriptor": "Neoplasms", "descriptor_ui": "D009369", "major_topic": false }, { "descriptor": "Programmed Cell Death 1 Receptor", "descriptor_ui": "D061026", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020 Feb", "date_precision": "unknown", "issue": "2", "normalized_date": null, "pages": "217-239", "proceedings_title": null, "publisher": "", "title": "International journal of clinical oncology", "volume": "25", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Japan Society of Clinical Oncology provisional clinical opinion for the diagnosis and use of immunotherapy in patients with deficient DNA mismatch repair tumors, cooperated by Japanese Society of Medical Oncology, First Edition.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Seizures are induced when subjects are exposed to severe hypoxia. It is followed by ventilatory fall-off and eventual respiratory arrest, which may underlie the pathophysiology of death in patients with epilepsy and severe respiratory disorders. However, the mechanisms of hypoxia-induced seizures have not been fully understood. Because astrocytes are involved in various neurological disorders, we aimed to investigate whether astrocytes are operational in seizure generation and respiratory arrest in a severe hypoxic condition. We examined the effects of astrocytic activation blockade on responses of EEG and ventilation to severe hypoxia. Adult mice were divided into two groups; in one group (n = 24) only vehicle was injected, and in the other group (n = 24) arundic acid, an inhibitory modulator of astrocytic activation, was administered before initiation of recording. After recording EEG and ventilation by whole body plethysmography in room air, the gas in the recording chamber was switched to 5% oxygen (nitrogen balanced) until a seizure and ventilatory depression occurred, followed by prompt switch back to room air. Severe hypoxia initially increased ventilation, followed by a seizure and ventilatory suppression in all mice examined. Fourteen mice without arundic acid showed respiratory arrest during loading of hypoxia. However, 22 mice pretreated with arundic acid did not suffer from respiratory arrest. Time from the onset of hypoxia to the occurrence of seizures was significantly longer in the group with arundic acid than that in the group without arundic acid. We suggest that blockade of astrocytic activation delays the occurrence of seizures and prevents respiratory arrest.", "classifications": [ { "id": "Yokota", "label": "Group Yokota", "parent": "Enomoto", "type": "group" }, { "id": "Enomoto", "label": "Team Enomoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Isato", "last_name": "Fukushi", "name": null }, { "creator_type": "author", "first_name": "Kotaro", "last_name": "Takeda", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Uchiyama", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Kurita", "name": null }, { "creator_type": "author", "first_name": "Mieczyslaw", "last_name": "Pokorski", "name": null }, { "creator_type": "author", "first_name": "Shigefumi", "last_name": "Yokota", "name": null }, { "creator_type": "author", "first_name": "Shuntaro", "last_name": "Okazaki", "name": null }, { "creator_type": "author", "first_name": "Jouji", "last_name": "Horiuchi", "name": null }, { "creator_type": "author", "first_name": "Yasuo", "last_name": "Mori", "name": null }, { "creator_type": "author", "first_name": "Yasumasa", "last_name": "Okada", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/cne.24828" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "31769022" } }, "mesh": [ { "descriptor": "Administration, Inhalation", "descriptor_ui": "D000280", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Astrocytes", "descriptor_ui": "D001253", "major_topic": false }, { "descriptor": "Caprylates", "descriptor_ui": "D002210", "major_topic": false }, { "descriptor": "Electroencephalography", "descriptor_ui": "D004569", "major_topic": false }, { "descriptor": "Hypoxia", "descriptor_ui": "D000860", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Respiration Disorders", "descriptor_ui": "D012120", "major_topic": false }, { "descriptor": "Seizures", "descriptor_ui": "D012640", "major_topic": false }, { "descriptor": "Severity of Illness Index", "descriptor_ui": "D012720", "major_topic": true } ], "publication": { "conference_name": null, "date": "2020 Jun", "date_precision": "unknown", "issue": "8", "normalized_date": null, "pages": "1257-1264", "proceedings_title": null, "publisher": "", "title": "The Journal of comparative neurology", "volume": "528", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Blockade of astrocytic activation delays the occurrence of severe hypoxia-induced seizure and respiratory arrest in mice.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: Depletion of ATP in renal tubular cells plays the central role in the pathogenesis of kidney diseases. Nevertheless, inability to visualize spatiotemporal in vivo ATP distribution and dynamics has hindered further analysis. METHODS: A novel mouse line systemically expressing an ATP biosensor (an ATP synthase subunit and two fluorophores) revealed spatiotemporal ATP dynamics at single-cell resolution during warm and cold ischemic reperfusion (IR) with two-photon microscopy. This experimental system enabled quantification of fibrosis 2 weeks after IR and assessment of the relationship between the ATP recovery in acute phase and fibrosis in chronic phase. RESULTS: Upon ischemia induction, the ATP levels of proximal tubule (PT) cells decreased to the nadir within a few minutes, whereas those of distal tubule (DT) cells decreased gradually up to 1 hour. Upon reperfusion, the recovery rate of ATP in PTs was slower with longer ischemia. In stark contrast, ATP in DTs was quickly rebounded irrespective of ischemia duration. Morphologic changes of mitochondria in the acute phase support the observation of different ATP dynamics in the two segments. Furthermore, slow and incomplete ATP recovery of PTs in the acute phase inversely correlated with fibrosis in the chronic phase. Ischemia under conditions of hypothermia resulted in more rapid and complete ATP recovery with less fibrosis, providing a proof of concept for use of hypothermia to protect kidney tissues. CONCLUSIONS: Visualizing spatiotemporal ATP dynamics during IR injury revealed higher sensitivity of PT cells to ischemia compared with DT cells in terms of energy metabolism. The ATP dynamics of PTs in AKI might provide prognostic information.", "classifications": [], "creators": [ { "creator_type": "author", "first_name": "Shinya", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Masamichi", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Jin", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Akiko", "last_name": "Mii", "name": null }, { "creator_type": "author", "first_name": "Shigenori", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Keiichi", "last_name": "Kaneko", "name": null }, { "creator_type": "author", "first_name": "Eiichiro", "last_name": "Uchino", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Shingo", "last_name": "Fukuma", "name": null }, { "creator_type": "author", "first_name": "Hiromi", "last_name": "Imamura", "name": null }, { "creator_type": "author", "first_name": "Michiyuki", "last_name": "Matsuda", "name": null }, { "creator_type": "author", "first_name": "Motoko", "last_name": "Yanagita", "name": null } ], "identifiers": { "doi": { "normalized": "10.1681/asn.2020050580" }, "pmcid": { "normalized": "PMC7790205" }, "pmid": { "normalized": "33046532" } }, "mesh": [ { "descriptor": "Acute Kidney Injury", "descriptor_ui": "D058186", "major_topic": false }, { "descriptor": "Adenosine Triphosphate", "descriptor_ui": "D000255", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Disease Models, Animal", "descriptor_ui": "D004195", "major_topic": false }, { "descriptor": "Kidney Tubules, Proximal", "descriptor_ui": "D007687", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Predictive Value of Tests", "descriptor_ui": "D011237", "major_topic": false }, { "descriptor": "Prognosis", "descriptor_ui": "D011379", "major_topic": false }, { "descriptor": "Reperfusion Injury", "descriptor_ui": "D015427", "major_topic": false }, { "descriptor": "Time Factors", "descriptor_ui": "D013997", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020 Dec", "date_precision": "unknown", "issue": "12", "normalized_date": null, "pages": "2855-2869", "proceedings_title": null, "publisher": "", "title": "Journal of the American Society of Nephrology : JASN", "volume": "31", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Spatiotemporal ATP Dynamics during AKI Predict Renal Prognosis.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "In Arabidopsis thaliana the ANGUSTIFOLIA (AN) gene regulates the width of leaves by controlling the diffuse growth of leaf cells in the medio-lateral direction. In the genome of the moss Physcomitrella patens, we found two normal ANs (PpAN1-1 and 1-2). Both PpAN1 genes complemented the A. thaliana an-1 mutant phenotypes. An analysis of spatiotemporal promoter activity of each PpAN1 gene, using transgenic lines that contained each PpAN1-promoter- uidA (GUS) gene, showed that both promoters are mainly active in the stems of haploid gametophores and in the middle to basal region of the young sporophyte that develops into the seta and foot. Analyses of the knockout lines for PpAN1-1 and PpAN1-2 genes suggested that these genes have partially redundant functions and regulate gametophore height by controlling diffuse cell growth in gametophore stems. In addition, the seta and foot were shorter and thicker in diploid sporophytes, suggesting that cell elongation was reduced in the longitudinal direction, whereas no defects were detected in tip-growing protonemata. These results indicate that both PpAN1 genes in P. patens function in diffuse growth of the haploid and diploid generations but not in tip growth. To visualize microtubule distribution in gametophore cells of P. patens, transformed lines expressing P. patens alpha-tubulin fused to sGFP were generated. Contrary to expectations, the orientation of microtubules in the tips of gametophores in the PpAN1-1/1-2 double-knockout lines was unchanged. The relationships among diffuse cell growth, cortical microtubules and AN proteins are discussed.", "classifications": [ { "id": "Sato", "label": "Group Sato", "parent": "Tsuchiya", "type": "group" }, { "id": "Tsuchiya", "label": "Team Tsuchiya", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yoshikazu", "last_name": "Hashida", "name": null }, { "creator_type": "author", "first_name": "Katsuaki", "last_name": "Takechi", "name": null }, { "creator_type": "author", "first_name": "Tomomi", "last_name": "Abiru", "name": null }, { "creator_type": "author", "first_name": "Noriyuki", "last_name": "Yabe", "name": null }, { "creator_type": "author", "first_name": "Hiroaki", "last_name": "Nagase", "name": null }, { "creator_type": "author", "first_name": "Koro", "last_name": "Hattori", "name": null }, { "creator_type": "author", "first_name": "Susumu", "last_name": "Takio", "name": null }, { "creator_type": "author", "first_name": "Yoshikatsu", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Mitsuyasu", "last_name": "Hasebe", "name": null }, { "creator_type": "author", "first_name": "Hirokazu", "last_name": "Tsukaya", "name": null }, { "creator_type": "author", "first_name": "Hiroyoshi", "last_name": "Takano", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/tpj.14592" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "31674691" } }, "mesh": [ { "descriptor": "Arabidopsis", "descriptor_ui": "D017360", "major_topic": false }, { "descriptor": "Arabidopsis Proteins", "descriptor_ui": "D029681", "major_topic": false }, { "descriptor": "Bryopsida", "descriptor_ui": "D019068", "major_topic": false }, { "descriptor": "Diploidy", "descriptor_ui": "D004171", "major_topic": false }, { "descriptor": "Gene Knockdown Techniques", "descriptor_ui": "D055785", "major_topic": false }, { "descriptor": "Genes, Plant", "descriptor_ui": "D017343", "major_topic": false }, { "descriptor": "Germ Cells, Plant", "descriptor_ui": "D055993", "major_topic": false }, { "descriptor": "Haploidy", "descriptor_ui": "D006238", "major_topic": false }, { "descriptor": "Phylogeny", "descriptor_ui": "D010802", "major_topic": false }, { "descriptor": "Plants, Genetically Modified", "descriptor_ui": "D030821", "major_topic": false }, { "descriptor": "Repressor Proteins", "descriptor_ui": "D012097", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020 Mar", "date_precision": "unknown", "issue": "6", "normalized_date": null, "pages": "1318-1330", "proceedings_title": null, "publisher": "", "title": "The Plant journal : for cell and molecular biology", "volume": "101", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Two ANGUSTIFOLIA genes regulate gametophore and sporophyte development in Physcomitrella patens.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The recent development of immune checkpoint inhibitors (ICIs) has led to promising advances in the treatment of patients with NSCLC and SCLC with advanced or metastatic disease. Most ICIs target programmed cell death protein 1 (PD-1) or programmed death ligand 1 (PD-L1) axis with the aim of restoring antitumor immunity. Multiple clinical trials for ICIs have evaluated a predictive value of PD-L1 protein expression in tumor cells and tumor-infiltrating immune cells (ICs) by immunohistochemistry (IHC), for which different assays with specific IHC platforms were applied. Of those, some PD-L1 IHC assays have been validated for the prescription of the corresponding agent for first- or second-line treatment. However, not all laboratories are equipped with the dedicated platforms, and many laboratories have set up in-house or laboratory-developed tests that are more affordable than the generally expensive clinical trial-validated assays. Although PD-L1 IHC test is now deployed in most pathology laboratories, its appropriate implementation and interpretation are critical as a predictive biomarker and can be challenging owing to the multiple antibody clones and platforms or assays available and given the typically small size of samples provided. Because many articles have been published since the issue of the IASLC Atlas of PD-L1 Immunohistochemistry Testing in Lung Cancer, this review by the IASLC Pathology Committee provides updates on the indications of ICIs for lung cancer in 2019 and discusses important considerations on preanalytical, analytical, and postanalytical aspects of PD-L1 IHC testing, including specimen type, validation of assays, external quality assurance, and training.", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Sylvie", "last_name": "Lantuejoul", "name": null }, { "creator_type": "author", "first_name": "Ming", "last_name": "Sound-Tsao", "name": null }, { "creator_type": "author", "first_name": "Wendy A.", "last_name": "Cooper", "name": null }, { "creator_type": "author", "first_name": "Nicolas", "last_name": "Girard", "name": null }, { "creator_type": "author", "first_name": "Fred R.", "last_name": "Hirsch", "name": null }, { "creator_type": "author", "first_name": "Anja C.", "last_name": "Roden", "name": null }, { "creator_type": "author", "first_name": "Fernando", "last_name": "Lopez-Rios", "name": null }, { "creator_type": "author", "first_name": "Deepali", "last_name": "Jain", "name": null }, { "creator_type": "author", "first_name": "Teh-Ying", "last_name": "Chou", "name": null }, { "creator_type": "author", "first_name": "Noriko", "last_name": "Motoi", "name": null }, { "creator_type": "author", "first_name": "Keith M.", "last_name": "Kerr", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null }, { "creator_type": "author", "first_name": "Elisabeth", "last_name": "Brambilla", "name": null }, { "creator_type": "author", "first_name": "John", "last_name": "Longshore", "name": null }, { "creator_type": "author", "first_name": "Mauro", "last_name": "Papotti", "name": null }, { "creator_type": "author", "first_name": "Lynette M.", "last_name": "Sholl", "name": null }, { "creator_type": "author", "first_name": "Erik", "last_name": "Thunnissen", "name": null }, { "creator_type": "author", "first_name": "Natasha", "last_name": "Rekhtman", "name": null }, { "creator_type": "author", "first_name": "Alain", "last_name": "Borczuk", "name": null }, { "creator_type": "author", "first_name": "Lukas", "last_name": "Bubendorf", "name": null }, { "creator_type": "author", "first_name": "Yuko", "last_name": "Minami", "name": null }, { "creator_type": "author", "first_name": "Mary Beth", "last_name": "Beasley", "name": null }, { "creator_type": "author", "first_name": "Johan", "last_name": "Botling", "name": null }, { "creator_type": "author", "first_name": "Gang", "last_name": "Chen", "name": null }, { "creator_type": "author", "first_name": "Jin-Haeng", "last_name": "Chung", "name": null }, { "creator_type": "author", "first_name": "Sanja", "last_name": "Dacic", "name": null }, { "creator_type": "author", "first_name": "David", "last_name": "Hwang", "name": null }, { "creator_type": "author", "first_name": "Dongmei", "last_name": "Lin", "name": null }, { "creator_type": "author", "first_name": "Andre", "last_name": "Moreira", "name": null }, { "creator_type": "author", "first_name": "Andrew G.", "last_name": "Nicholson", "name": null }, { "creator_type": "author", "first_name": "Masayuki", "last_name": "Noguchi", "name": null }, { "creator_type": "author", "first_name": "Giuseppe", "last_name": "Pelosi", "name": null }, { "creator_type": "author", "first_name": "Claudia", "last_name": "Poleri", "name": null }, { "creator_type": "author", "first_name": "William", "last_name": "Travis", "name": null }, { "creator_type": "author", "first_name": "Akihiko", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Jillian B.", "last_name": "Daigneault", "name": null }, { "creator_type": "author", "first_name": "Ignacio I.", "last_name": "Wistuba", "name": null }, { "creator_type": "author", "first_name": "Mari", "last_name": "Mino-Kenudson", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.jtho.2019.12.107" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "31870882" } }, "mesh": [ { "descriptor": "B7-H1 Antigen", "descriptor_ui": "D060890", "major_topic": false }, { "descriptor": "Biomarkers, Tumor", "descriptor_ui": "D014408", "major_topic": false }, { "descriptor": "Carcinoma, Non-Small-Cell Lung", "descriptor_ui": "D002289", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Immunohistochemistry", "descriptor_ui": "D007150", "major_topic": false }, { "descriptor": "Lung Neoplasms", "descriptor_ui": "D008175", "major_topic": true } ], "publication": { "conference_name": null, "date": "2020 Apr", "date_precision": "unknown", "issue": "4", "normalized_date": null, "pages": "499-519", "proceedings_title": null, "publisher": "", "title": "Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer", "volume": "15", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "PD-L1 Testing for Lung Cancer in 2019: Perspective From the IASLC Pathology Committee.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Squamous cell carcinoma of the head and neck (SCCHN) is a malignancy with poor outcomes, thus novel therapies are urgently needed. We recently showed that WHSC1 is necessary for the viability of SCCHN cells through H3K36 di-methylation. Here, we report the identification of its novel substrate, histone H1, and that WHSC1-mediated H1.4K85 mono-methylation may enhance stemness features in SCCHN cells. To identify proteins interacting with WHSC1 in SCCHN cells, WHSC1 immunoprecipitation and mass spectrometry identified H1 as a WHSC1-interacting candidate. In vitro methyltransferase assays showed that WHSC1 mono-methylates H1 at K85. We generated an H1K85 mono-methylation-specific antibody and confirmed that this methylation occurs in vivo. Sphere formation assays using SCC-35 cells stably expressing either wild-type (FLAG-H1.4-WT) or mutated (FLAG-H1.4K85A) vector with lysine 85 to alanine substitution which is not methylated, indicated a higher number of spheres in SCC-35 cells expressing the wild type than those with the mutant vector. SCC-35 cells expressing the wild type H1.4 proliferated faster than those expressing the mutated vector. RNA sequencing, RT-PCR and Western blotting of the FLAG-H1.4-WT or FLAG-H1.4K85A SCC-35 cells revealed that OCT4 levels were higher in wild type compared to mutant cells. These results were reproduced in SCC-35 cells genetically modified with CRISPR to express H1.4K85R. Chromatin immunoprecipitation showed that FLAG-H1.4K85A had decreased occupancy in the OCT4 gene compared to FLAG-H1.4-WT. This study supports that WHSC1 mono-methylates H1.4 at K85, it induces transcriptional activation of OCT4 and stemness features in SCCHN cells, providing rationale to target H1.4K85 mono-methylation through WHSC1 in SCCHN.", "classifications": [ { "id": "Hamamoto", "label": "Group Hamamoto", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Vassiliki", "last_name": "Saloura", "name": null }, { "creator_type": "author", "first_name": "Theodore", "last_name": "Vougiouklakis", "name": null }, { "creator_type": "author", "first_name": "Riyue", "last_name": "Bao", "name": null }, { "creator_type": "author", "first_name": "Sohyoung", "last_name": "Kim", "name": null }, { "creator_type": "author", "first_name": "Songjoon", "last_name": "Baek", "name": null }, { "creator_type": "author", "first_name": "Makda", "last_name": "Zewde", "name": null }, { "creator_type": "author", "first_name": "Benjamin", "last_name": "Bernard", "name": null }, { "creator_type": "author", "first_name": "Kyunghee", "last_name": "Burkitt", "name": null }, { "creator_type": "author", "first_name": "Nupur", "last_name": "Nigam", "name": null }, { "creator_type": "author", "first_name": "Evgeny", "last_name": "Izumchenko", "name": null }, { "creator_type": "author", "first_name": "Naoshi", "last_name": "Dohmae", "name": null }, { "creator_type": "author", "first_name": "Ryuji", "last_name": "Hamamoto", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Nakamura", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.neo.2020.05.002" }, "pmcid": { "normalized": "PMC7265065" }, "pmid": { "normalized": "32497898" } }, "mesh": [ { "descriptor": "Apoptosis", "descriptor_ui": "D017209", "major_topic": false }, { "descriptor": "Cell Proliferation", "descriptor_ui": "D049109", "major_topic": false }, { "descriptor": "Head and Neck Neoplasms", "descriptor_ui": "D006258", "major_topic": false }, { "descriptor": "Histone-Lysine N-Methyltransferase", "descriptor_ui": "D011495", "major_topic": false }, { "descriptor": "Histones", "descriptor_ui": "D006657", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Neoplastic Stem Cells", "descriptor_ui": "D014411", "major_topic": false }, { "descriptor": "Repressor Proteins", "descriptor_ui": "D012097", "major_topic": false }, { "descriptor": "Squamous Cell Carcinoma of Head and Neck", "descriptor_ui": "D000077195", "major_topic": false }, { "descriptor": "Tumor Cells, Cultured", "descriptor_ui": "D014407", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020 Aug", "date_precision": "unknown", "issue": "8", "normalized_date": null, "pages": "283-293", "proceedings_title": null, "publisher": "", "title": "Neoplasia (New York, N.Y.)", "volume": "22", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "WHSC1 monomethylates histone H1 and induces stem-cell like features in squamous cell carcinoma of the head and neck.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Taking advantage of the recent development of genetically-defined photo-activatable actuator molecules, cellular functions, including gene expression, can be controlled by exposure to light. Such optogenetic strategies enable precise temporal and spatial manipulation of targeted single cells or groups of cells at a level hitherto impossible. In this review, we introduce light-controllable gene expression systems exploiting blue or red/far-red wavelengths and discuss their inherent properties potentially affecting induced downstream gene expression patterns. We also discuss recent advances in optical devices that will extend the application of optical gene expression control technologies into many different areas of biology and medicine.", "classifications": [ { "id": "Imayoshi", "label": "Group Imayoshi", "parent": "Imayoshi", "type": "group" }, { "id": "Imayoshi", "label": "Team Imayoshi", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Mayumi", "last_name": "Yamada", "name": null }, { "creator_type": "author", "first_name": "Shinji C.", "last_name": "Nagasaki", "name": null }, { "creator_type": "author", "first_name": "Takeaki", "last_name": "Ozawa", "name": null }, { "creator_type": "author", "first_name": "Itaru", "last_name": "Imayoshi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.neures.2019.12.018" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "31923448" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cryptochromes", "descriptor_ui": "D056931", "major_topic": false }, { "descriptor": "Gene Expression", "descriptor_ui": "D015870", "major_topic": true }, { "descriptor": "Optogenetics", "descriptor_ui": "D062308", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020 Mar", "date_precision": "unknown", "issue": "", "normalized_date": null, "pages": "66-77", "proceedings_title": null, "publisher": "", "title": "Neuroscience research", "volume": "152", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Light-mediated control of Gene expression in mammalian cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "In multi-ciliated cells, directed and synchronous ciliary beating in the apical membrane occurs through appropriate configuration of basal bodies (BBs, roots of cilia). Although it has been experimentally shown that the position and orientation of BBs are coordinated by apical cytoskeletons (CSKs), such as microtubules (MTs), and planar cell polarity (PCP), the underlying mechanism for achieving the patterning of BBs is not yet understood. In this study, we propose that polarity in bundles of apical MTs play a crucial role in the patterning of BBs. First, the necessity of the polarity was discussed by theoretical consideration on the symmetry of the system. The existence of the polarity was investigated by measuring relative angles between the MTs and BBs using published experimental data. Next, a mathematical model for BB patterning was derived by combining the polarity and self-organizational ability of CSKs. In the model, BBs were treated as finite-size particles in the medium of CSKs and excluded volume effects between BBs and CSKs were taken into account. The model reproduces the various experimental observations, including normal and drug-treated phenotypes. Our model with polarity provides a coherent and testable mechanism for apical BB pattern formation. We have also discussed the implication of our study on cell chirality.", "classifications": [ { "id": "Ishihara", "label": "Group Ishihara", "parent": "Sawai", "type": "group" }, { "id": "Sawai", "label": "Team Sawai", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Toshinori", "last_name": "Namba", "name": null }, { "creator_type": "author", "first_name": "Shuji", "last_name": "Ishihara", "name": null } ], "identifiers": { "doi": { "normalized": "10.1371/journal.pcbi.1007649" }, "pmcid": { "normalized": "PMC7055923" }, "pmid": { "normalized": "32084125" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Basal Bodies", "descriptor_ui": "D064652", "major_topic": false }, { "descriptor": "Cell Membrane", "descriptor_ui": "D002462", "major_topic": false }, { "descriptor": "Cell Polarity", "descriptor_ui": "D016764", "major_topic": false }, { "descriptor": "Cilia", "descriptor_ui": "D002923", "major_topic": false }, { "descriptor": "Computer Simulation", "descriptor_ui": "D003198", "major_topic": false }, { "descriptor": "Cytoskeleton", "descriptor_ui": "D003599", "major_topic": false }, { "descriptor": "Elasticity", "descriptor_ui": "D004548", "major_topic": false }, { "descriptor": "Epithelial Cells", "descriptor_ui": "D004847", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Microtubules", "descriptor_ui": "D008870", "major_topic": false }, { "descriptor": "Models, Theoretical", "descriptor_ui": "D008962", "major_topic": false }, { "descriptor": "Nocodazole", "descriptor_ui": "D015739", "major_topic": false }, { "descriptor": "Phenotype", "descriptor_ui": "D010641", "major_topic": false }, { "descriptor": "Trachea", "descriptor_ui": "D014132", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020 Feb", "date_precision": "unknown", "issue": "2", "normalized_date": null, "pages": "e1007649", "proceedings_title": null, "publisher": "", "title": "PLoS computational biology", "volume": "16", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Cytoskeleton polarity is essential in determining orientational order in basal bodies of multi-ciliated cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Genomes are spatiotemporally organized within the cell nucleus. Genome-wide chromosome conformation capture (Hi-C) technologies have uncovered the 3D genome organization. Furthermore, live-cell imaging experiments have revealed that genomes are functional in 4D. Although computational modeling methods can convert 2D Hi-C data into population-averaged static 3D genome models, exploring 4D genome nature based on 2D Hi-C data remains lacking. Here, we describe a 4D simulation method, PHi-C (polymer dynamics deciphered from Hi-C data), that depicts 4D genome features from 2D Hi-C data by polymer modeling. PHi-C allows users to interpret 2D Hi-C data as physical interaction parameters within single chromosomes. The physical interaction parameters can then be used in the simulations and analyses to demonstrate dynamic characteristics of genomic loci and chromosomes as observed in live-cell imaging experiments. PHi-C is available at https://github.com/soyashinkai/PHi-C.", "classifications": [ { "id": "Onami", "label": "Group Onami", "parent": "Fujiwara", "type": "group" }, { "id": "Fujiwara", "label": "Team Fujiwara", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Soya", "last_name": "Shinkai", "name": null }, { "creator_type": "author", "first_name": "Masaki", "last_name": "Nakagawa", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Sugawara", "name": null }, { "creator_type": "author", "first_name": "Yuichi", "last_name": "Togashi", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Ochiai", "name": null }, { "creator_type": "author", "first_name": "Ryuichiro", "last_name": "Nakato", "name": null }, { "creator_type": "author", "first_name": "Yuichi", "last_name": "Taniguchi", "name": null }, { "creator_type": "author", "first_name": "Shuichi", "last_name": "Onami", "name": null } ], "identifiers": { "doi": { "normalized": "10.1093/nargab/lqaa020" }, "pmcid": { "normalized": "PMC7671433" }, "pmid": { "normalized": "33575580" } }, "mesh": [], "publication": { "conference_name": null, "date": "2020 Jun", "date_precision": "unknown", "issue": "2", "normalized_date": null, "pages": "lqaa020", "proceedings_title": null, "publisher": "", "title": "NAR genomics and bioinformatics", "volume": "2", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "PHi-C: deciphering Hi-C data into polymer dynamics.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Intracellular reactions are intrinsically stochastic. Nonetheless, cells can reliably respond to the changing environment by sensing their target molecules sensitively and specifically, even with the existence of abundant structurally-similar non-target molecules. The mechanism of how the cells can balance and achieve such different characteristics is not yet fully understood. In this work, we demonstrate that these characteristics can be attained by a ligand-induced stochastic cluster formation of receptors via the noise-induced symmetry breaking, in which the intrinsic stochasticity works to enhance sensitivity and specificity. We also show that the noise-induced cluster formation enables cells to detect the target ligand reliably by compensating the abundant non-target ligands in the environment. The proposed mechanism may lead to a deeper understanding of a biological function of the receptor clustering and provide an alternative candidate for the reliable ligand detection to the kinetic proofreading.", "classifications": [ { "id": "Kobayashi", "label": "Group Kobayashi", "parent": "Wakamoto", "type": "group" }, { "id": "Wakamoto", "label": "Team Wakamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Masashi K.", "last_name": "Kajita", "name": null }, { "creator_type": "author", "first_name": "Kazuyuki", "last_name": "Aihara", "name": null }, { "creator_type": "author", "first_name": "Tetsuya J.", "last_name": "Kobayashi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1063/1.5140714" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "32013460" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Computer Simulation", "descriptor_ui": "D003198", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Ligands", "descriptor_ui": "D008024", "major_topic": false }, { "descriptor": "Models, Biological", "descriptor_ui": "D008954", "major_topic": true }, { "descriptor": "Receptors, Cell Surface", "descriptor_ui": "D011956", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020 Jan", "date_precision": "unknown", "issue": "1", "normalized_date": null, "pages": "011104", "proceedings_title": null, "publisher": "", "title": "Chaos (Woodbury, N.Y.)", "volume": "30", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Reliable target ligand detection by noise-induced receptor cluster formation.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The invention of two-photon excitation microscopes widens the potential application of intravital microscopy (IVM) to the broad field of experimental pathology. Moreover, the recent development of fluorescent protein-based, genetically encoded biosensors provides an ideal tool to visualize the cell function in live animals. We start from a brief review of IVM with two-photon excitation microscopes and genetically encoded biosensors based on the principle of Forster resonance energy transfer (FRET). Then, we describe how IVM using biosensors has revealed the pathogenesis of several disease models.", "classifications": [], "creators": [ { "creator_type": "author", "first_name": "Michiyuki", "last_name": "Matsuda", "name": null }, { "creator_type": "author", "first_name": "Kenta", "last_name": "Terai", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/pin.12925" }, "pmcid": { "normalized": "PMC7383902" }, "pmid": { "normalized": "32270554" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Biosensing Techniques", "descriptor_ui": "D015374", "major_topic": false }, { "descriptor": "Disease Models, Animal", "descriptor_ui": "D004195", "major_topic": false }, { "descriptor": "Fluorescence Resonance Energy Transfer", "descriptor_ui": "D031541", "major_topic": false }, { "descriptor": "Intravital Microscopy", "descriptor_ui": "D000069416", "major_topic": false }, { "descriptor": "Microscopy, Fluorescence", "descriptor_ui": "D008856", "major_topic": false }, { "descriptor": "Pathology", "descriptor_ui": "D010336", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020 Jul", "date_precision": "unknown", "issue": "7", "normalized_date": null, "pages": "379-390", "proceedings_title": null, "publisher": "", "title": "Pathology international", "volume": "70", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Experimental pathology by intravital microscopy and genetically encoded fluorescent biosensors.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Currently, there is no established guidance on how to process and evaluate resected lung cancer specimens after neoadjuvant therapy in the setting of clinical trials and clinical practice. There is also a lack of precise definitions on the degree of pathologic response, including major pathologic response or complete pathologic response. For other cancers such as osteosarcoma and colorectal, breast, and esophageal carcinomas, there have been multiple studies investigating pathologic assessment of the effects of neoadjuvant therapy, including some detailed recommendations on how to handle these specimens. A comprehensive mapping approach to gross and histologic processing of osteosarcomas after induction therapy has been used for over 40 years. The purpose of this article is to outline detailed recommendations on how to process lung cancer resection specimens and to define pathologic response, including major pathologic response or complete pathologic response after neoadjuvant therapy. A standardized approach is recommended to assess the percentages of (1) viable tumor, (2) necrosis, and (3) stroma (including inflammation and fibrosis) with a total adding up to 100%. This is recommended for all systemic therapies, including chemotherapy, chemoradiation, molecular-targeted therapy, immunotherapy, or any future novel therapies yet to be discovered, whether administered alone or in combination. Specific issues may differ for certain therapies such as immunotherapy, but the grossing process should be similar, and the histologic evaluation should contain these basic elements. Standard pathologic response assessment should allow for comparisons between different therapies and correlations with disease-free survival and overall survival in ongoing and future trials. The International Association for the Study of Lung Cancer has an effort to collect such data from existing and future clinical trials. These recommendations are intended as guidance for clinical trials, although it is hoped they can be viewed as suggestion for good clinical practice outside of clinical trials, to improve consistency of pathologic assessment of treatment response.", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "William D.", "last_name": "Travis", "name": null }, { "creator_type": "author", "first_name": "Sanja", "last_name": "Dacic", "name": null }, { "creator_type": "author", "first_name": "Ignacio", "last_name": "Wistuba", "name": null }, { "creator_type": "author", "first_name": "Lynette", "last_name": "Sholl", "name": null }, { "creator_type": "author", "first_name": "Prasad", "last_name": "Adusumilli", "name": null }, { "creator_type": "author", "first_name": "Lukas", "last_name": "Bubendorf", "name": null }, { "creator_type": "author", "first_name": "Paul", "last_name": "Bunn", "name": null }, { "creator_type": "author", "first_name": "Tina", "last_name": "Cascone", "name": null }, { "creator_type": "author", "first_name": "Jamie", "last_name": "Chaft", "name": null }, { "creator_type": "author", "first_name": "Gang", "last_name": "Chen", "name": null }, { "creator_type": "author", "first_name": "Teh-Ying", "last_name": "Chou", "name": null }, { "creator_type": "author", "first_name": "Wendy", "last_name": "Cooper", "name": null }, { "creator_type": "author", "first_name": "Jeremy J.", "last_name": "Erasmus", "name": null }, { "creator_type": "author", "first_name": "Carlos Gil", "last_name": "Ferreira", "name": null }, { "creator_type": "author", "first_name": "Jin-Mo", "last_name": "Goo", "name": null }, { "creator_type": "author", "first_name": "John", "last_name": "Heymach", "name": null }, { "creator_type": "author", "first_name": "Fred R.", "last_name": "Hirsch", "name": null }, { "creator_type": "author", "first_name": "Hidehito", "last_name": "Horinouchi", "name": null }, { "creator_type": "author", "first_name": "Keith", "last_name": "Kerr", "name": null }, { "creator_type": "author", "first_name": "Mark", "last_name": "Kris", "name": null }, { "creator_type": "author", "first_name": "Deepali", "last_name": "Jain", "name": null }, { "creator_type": "author", "first_name": "Young T.", "last_name": "Kim", "name": null }, { "creator_type": "author", "first_name": "Fernando", "last_name": "Lopez-Rios", "name": null }, { "creator_type": "author", "first_name": "Shun", "last_name": "Lu", "name": null }, { "creator_type": "author", "first_name": "Tetsuya", "last_name": "Mitsudomi", "name": null }, { "creator_type": "author", "first_name": "Andre", "last_name": "Moreira", "name": null }, { "creator_type": "author", "first_name": "Noriko", "last_name": "Motoi", "name": null }, { "creator_type": "author", "first_name": "Andrew G.", "last_name": "Nicholson", "name": null }, { "creator_type": "author", "first_name": "Ricardo", "last_name": "Oliveira", "name": null }, { "creator_type": "author", "first_name": "Mauro", "last_name": "Papotti", "name": null }, { "creator_type": "author", "first_name": "Ugo", "last_name": "Pastorino", "name": null }, { "creator_type": "author", "first_name": "Luis", "last_name": "Paz-Ares", "name": null }, { "creator_type": "author", "first_name": "Giuseppe", "last_name": "Pelosi", "name": null }, { "creator_type": "author", "first_name": "Claudia", "last_name": "Poleri", "name": null }, { "creator_type": "author", "first_name": "Mariano", "last_name": "Provencio", "name": null }, { "creator_type": "author", "first_name": "Anja C.", "last_name": "Roden", "name": null }, { "creator_type": "author", "first_name": "Giorgio", "last_name": "Scagliotti", "name": null }, { "creator_type": "author", "first_name": "Stephen G.", "last_name": "Swisher", "name": null }, { "creator_type": "author", "first_name": "Erik", "last_name": "Thunnissen", "name": null }, { "creator_type": "author", "first_name": "Ming S.", "last_name": "Tsao", "name": null }, { "creator_type": "author", "first_name": "Johan", "last_name": "Vansteenkiste", "name": null }, { "creator_type": "author", "first_name": "Walter", "last_name": "Weder", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.jtho.2020.01.005" }, "pmcid": { "normalized": "PMC8173999" }, "pmid": { "normalized": "32004713" } }, "mesh": [ { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Lung", "descriptor_ui": "D008168", "major_topic": false }, { "descriptor": "Lung Neoplasms", "descriptor_ui": "D008175", "major_topic": true }, { "descriptor": "Neoadjuvant Therapy", "descriptor_ui": "D020360", "major_topic": true } ], "publication": { "conference_name": null, "date": "2020 May", "date_precision": "unknown", "issue": "5", "normalized_date": null, "pages": "709-740", "proceedings_title": null, "publisher": "", "title": "Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer", "volume": "15", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "IASLC Multidisciplinary Recommendations for Pathologic Assessment of Lung Cancer Resection Specimens After Neoadjuvant Therapy.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The year 2019 was considered to be the first year of cancer genome medicine in Japan, with three gene-panel tests using next-generation sequencing (NGS) techniques being introduced into clinical practice. Among the three tests, the Oncomine CDx Target test was approved under the category of regular molecular testing for lung cancer, which meant that this test could be used to select patients for molecularly targeted drugs. Conversely, the other two tests, NCC OncoPanel and FoundationOne CDx, were assigned to be used under the National Cancer Genome Medicine Network, and implementation was restricted to patients for whom standard treatment was completed or expected to be completed. These NGS tests can detect a series of genetic alterations in individual tumors, which further promotes the development of therapeutic agents and elucidates molecular pathways. The NGS tests require appropriate tissue size and tumor cell content, which can be accessed only by pathologists. In this report, we review the current reimbursement schema in our national healthcare policy and the requirements of the specimens for NGS testing based on the recently published 'Guidance of Gene-panel Testing Using Next-Generation Sequencers for Lung Cancer', by the Japanese Society of Lung Cancer.", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null }, { "creator_type": "author", "first_name": "Kuniko", "last_name": "Sunami", "name": null }, { "creator_type": "author", "first_name": "Koichi", "last_name": "Goto", "name": null }, { "creator_type": "author", "first_name": "Kazuto", "last_name": "Nishio", "name": null }, { "creator_type": "author", "first_name": "Naoko", "last_name": "Aragane", "name": null }, { "creator_type": "author", "first_name": "Sadakatsu", "last_name": "Ikeda", "name": null }, { "creator_type": "author", "first_name": "Akira", "last_name": "Inoue", "name": null }, { "creator_type": "author", "first_name": "Ichiro", "last_name": "Kinoshita", "name": null }, { "creator_type": "author", "first_name": "Hideharu", "last_name": "Kimura", "name": null }, { "creator_type": "author", "first_name": "Tomohiro", "last_name": "Sakamoto", "name": null }, { "creator_type": "author", "first_name": "Miyako", "last_name": "Satouchi", "name": null }, { "creator_type": "author", "first_name": "Junichi", "last_name": "Shimizu", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Tsuta", "name": null }, { "creator_type": "author", "first_name": "Shinichi", "last_name": "Toyooka", "name": null }, { "creator_type": "author", "first_name": "Kazumi", "last_name": "Nishino", "name": null }, { "creator_type": "author", "first_name": "Yutaka", "last_name": "Hatanaka", "name": null }, { "creator_type": "author", "first_name": "Shingo", "last_name": "Matsumoto", "name": null }, { "creator_type": "author", "first_name": "Masashi", "last_name": "Mikubo", "name": null }, { "creator_type": "author", "first_name": "Tomoyuki", "last_name": "Yokose", "name": null }, { "creator_type": "author", "first_name": "Hirotoshi", "last_name": "Dosaka-Akita", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/pin.13023" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "32956529" } }, "mesh": [ { "descriptor": "DNA, Neoplasm", "descriptor_ui": "D004273", "major_topic": false }, { "descriptor": "Genetic Testing", "descriptor_ui": "D005820", "major_topic": true }, { "descriptor": "High-Throughput Nucleotide Sequencing", "descriptor_ui": "D059014", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Lung Neoplasms", "descriptor_ui": "D008175", "major_topic": true }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": false }, { "descriptor": "Pathology, Molecular", "descriptor_ui": "D057089", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020 Dec", "date_precision": "unknown", "issue": "12", "normalized_date": null, "pages": "921-931", "proceedings_title": null, "publisher": "", "title": "Pathology international", "volume": "70", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Multiplex gene-panel testing for lung cancer patients.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Inosine pranobex (IP) is a synthetic immunomodulating compound, indicated for use in the treatment of human papillomavirus-associated warts and subacute sclerosing panencephalitis. Previous studies demonstrate that the immunomodulatory activity of IP is characterized by enhanced lymphocyte proliferation, cytokine production, and NK cell cytotoxicity. The activation of NKG2D signaling on NK cells, CD8(+) T cells, and gammadelta T cells also produces these outcomes. We hypothesized that IP alters cellular immunity through the induction of NKG2D ligand expression on target cells, thereby enhancing immune cell activation through the NKG2D receptor. We tested this hypothesis and show that exposure of target cells to IP leads to increased expression of multiple NKG2D ligands. Using both targeted metabolic interventions and unbiased metabolomic studies, we found that IP causes an increase in intracellular concentration of purine nucleotides and tricarboxylic acid (TCA) cycle intermediates and NKG2D ligand induction. The degree of NKG2D ligand induction was functionally significant, leading to increased NKG2D-dependent target cell immunogenicity. These findings demonstrate that the immunomodulatory properties of IP are due to metabolic activation with NKG2D ligand induction.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Michael T.", "last_name": "McCarthy", "name": null }, { "creator_type": "author", "first_name": "Da", "last_name": "Lin", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Julie", "last_name": "Adam", "name": null }, { "creator_type": "author", "first_name": "Christopher A.", "last_name": "O'Callaghan", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/eji.201847948" }, "pmcid": { "normalized": "PMC6972573" }, "pmid": { "normalized": "31434164" } }, "mesh": [ { "descriptor": "Activation, Metabolic", "descriptor_ui": "D065767", "major_topic": false }, { "descriptor": "Adjuvants, Immunologic", "descriptor_ui": "D000276", "major_topic": false }, { "descriptor": "Cytotoxicity, Immunologic", "descriptor_ui": "D003602", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Inosine Pranobex", "descriptor_ui": "D007542", "major_topic": false }, { "descriptor": "Killer Cells, Natural", "descriptor_ui": "D007694", "major_topic": false }, { "descriptor": "Ligands", "descriptor_ui": "D008024", "major_topic": false }, { "descriptor": "NK Cell Lectin-Like Receptor Subfamily K", "descriptor_ui": "D055655", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020 Jan", "date_precision": "unknown", "issue": "1", "normalized_date": null, "pages": "130-137", "proceedings_title": null, "publisher": "", "title": "European journal of immunology", "volume": "50", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Inosine pranobex enhances human NK cell cytotoxicity by inducing metabolic activation and NKG2D ligand expression.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Kohei", "last_name": "Matsuda", "name": null }, { "creator_type": "author", "first_name": "Jumpei", "last_name": "Kashima", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.jtho.2020.07.017" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "32981612" } }, "mesh": [ { "descriptor": "Biomarkers, Tumor", "descriptor_ui": "D014408", "major_topic": false }, { "descriptor": "Carcinoma", "descriptor_ui": "D002277", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Immunohistochemistry", "descriptor_ui": "D007150", "major_topic": false }, { "descriptor": "Lung Neoplasms", "descriptor_ui": "D008175", "major_topic": true }, { "descriptor": "Protein Isoforms", "descriptor_ui": "D020033", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020 Oct", "date_precision": "unknown", "issue": "10", "normalized_date": null, "pages": "e176-e178", "proceedings_title": null, "publisher": "", "title": "Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer", "volume": "15", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "The Isoform Matters in NUT Carcinoma: A Diagnostic Pitfall of p40 Immunohistochemistry.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Cells respond to oxidative stress by inducing intracellular signaling, including stress-activated p38 and JNK MAPK (SAPK) pathways, but the underlying mechanisms remain unclear. Here, we report that the MAP three kinase 1 (MTK1) SAPK kinase kinase (SAPKKK) functions as an oxidative-stress sensor that perceives the cellular redox state and transduces it into SAPK signaling. Following oxidative stress, MTK1 is rapidly oxidized and gradually reduced at evolutionarily conserved cysteine residues. These coupled oxidation-reduction modifications of MTK1 elicit its catalytic activity. Gene knockout experiments showed that oxidative stress-induced SAPK signaling is mediated by coordinated activation of the two SAPKKKs, MTK1 and apoptosis signal-regulating kinase 1 (ASK1), which have different time and dose-response characteristics. The MTK1-mediated redox sensing system is crucial for delayed and sustained SAPK activity and dictates cell fate decisions including cell death and interleukin-6 production. Our results delineate a molecular mechanism by which cells generate optimal biological responses under fluctuating redox environments.", "classifications": [ { "id": "Takekawa", "label": "Group Takekawa", "parent": "Takekawa", "type": "group" }, { "id": "Takekawa", "label": "Team Takekawa", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Moe", "last_name": "Matsushita", "name": null }, { "creator_type": "author", "first_name": "Takanori", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Hisashi", "last_name": "Moriizumi", "name": null }, { "creator_type": "author", "first_name": "Hiroaki", "last_name": "Miki", "name": null }, { "creator_type": "author", "first_name": "Mutsuhiro", "last_name": "Takekawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1126/sciadv.aay9778" }, "pmcid": { "normalized": "PMC7314524" }, "pmid": { "normalized": "32637591" } }, "mesh": [], "publication": { "conference_name": null, "date": "2020 Jun", "date_precision": "unknown", "issue": "26", "normalized_date": null, "pages": "eaay9778", "proceedings_title": null, "publisher": "", "title": "Science advances", "volume": "6", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Stress-responsive MTK1 SAPKKK serves as a redox sensor that mediates delayed and sustained activation of SAPKs by oxidative stress.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Bronchiolar adenoma (BA) of the lung is a rare benign neoplasm. Because of a chest abnormal shadow indicated by health checkup, a 77-year-old female nonsmoker underwent computed tomography, revealing an 8 mm ground glass nodule in the peripheral field of the right lower lobe. Wedge resection of the nodule was performed, with a frozen diagnosis of primary lung adenocarcinoma. The localized, 8 x 4 x 3 mm-sized, jelly-like mass microscopically revealed a lepidic-growing lesion composed of ciliated columnar cells, mucous cells and basal cells surrounded by mucin pool. Neither nuclear atypia nor mitotic activity was noted. Immunohistochemically, the ciliated, mucous and basal cells were positive for TTF-1 and p16(INK4a) . Mucous cells were positive for napsin A and focally expressed MUC5AC. MUC6 was negative. Basal cells were positive for CK5/6, p40, p63 and podoplanin. Human papillomavirus genome was undetectable by in situ hybridization. Ultrastructurally, the bronchiolar epithelial tubules consisted of two layers, the inner nonciliated microvillous cells and the outer basal-like cells, and some of the inner cells were filled with mucin granules in cytoplasm. Molecular analysis of the tumor failed to show driver mutations. The final diagnosis was distal-type BA. The postoperative course was uneventful for 6 months.", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Mitsuhiro", "last_name": "Tachibana", "name": null }, { "creator_type": "author", "first_name": "Masao", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Jun", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Tadahiro", "last_name": "Isono", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null }, { "creator_type": "author", "first_name": "Yutaka", "last_name": "Tsutsumi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/pin.12904" }, "pmcid": { "normalized": "PMC7079048" }, "pmid": { "normalized": "32030846" } }, "mesh": [ { "descriptor": "Adenocarcinoma of Lung", "descriptor_ui": "D000077192", "major_topic": false }, { "descriptor": "Adenoma", "descriptor_ui": "D000236", "major_topic": false }, { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Bronchioles", "descriptor_ui": "D055745", "major_topic": false }, { "descriptor": "Cyclin-Dependent Kinase Inhibitor p16", "descriptor_ui": "D019941", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Goblet Cells", "descriptor_ui": "D020397", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Immunohistochemistry", "descriptor_ui": "D007150", "major_topic": false }, { "descriptor": "Lung Neoplasms", "descriptor_ui": "D008175", "major_topic": false }, { "descriptor": "Microscopy, Electron", "descriptor_ui": "D008854", "major_topic": false }, { "descriptor": "Mucins", "descriptor_ui": "D009077", "major_topic": false }, { "descriptor": "Tomography, X-Ray Computed", "descriptor_ui": "D014057", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020 Mar", "date_precision": "unknown", "issue": "3", "normalized_date": null, "pages": "179-185", "proceedings_title": null, "publisher": "", "title": "Pathology international", "volume": "70", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Distal-type bronchiolar adenoma of the lung expressing p16(INK4a) - morphologic, immunohistochemical, ultrastructural and genomic analysis - report of a case and review of the literature.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Single-cell RNA sequencing (scRNA-seq) is the leading technique for characterizing the transcriptomes of individual cells in a sample. The latest protocols are scalable to thousands of cells and are being used to compile cell atlases of tissues, organs and organisms. However, the protocols differ substantially with respect to their RNA capture efficiency, bias, scale and costs, and their relative advantages for different applications are unclear. In the present study, we generated benchmark datasets to systematically evaluate protocols in terms of their power to comprehensively describe cell types and states. We performed a multicenter study comparing 13 commonly used scRNA-seq and single-nucleus RNA-seq protocols applied to a heterogeneous reference sample resource. Comparative analysis revealed marked differences in protocol performance. The protocols differed in library complexity and their ability to detect cell-type markers, impacting their predictive value and suitability for integration into reference cell atlases. These results provide guidance both for individual researchers and for consortium projects such as the Human Cell Atlas.", "classifications": [ { "id": "Nikaido", "label": "Group Nikaido", "parent": "Fujiwara", "type": "group" }, { "id": "Fujiwara", "label": "Team Fujiwara", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Elisabetta", "last_name": "Mereu", "name": null }, { "creator_type": "author", "first_name": "Atefeh", "last_name": "Lafzi", "name": null }, { "creator_type": "author", "first_name": "Catia", "last_name": "Moutinho", "name": null }, { "creator_type": "author", "first_name": "Christoph", "last_name": "Ziegenhain", "name": null }, { "creator_type": "author", "first_name": "Davis J.", "last_name": "McCarthy", "name": null }, { "creator_type": "author", "first_name": "Adrian", "last_name": "Alvarez-Varela", "name": null }, { "creator_type": "author", "first_name": "Eduard", "last_name": "Batlle", "name": null }, { "creator_type": "author", "first_name": "", "last_name": "Sagar", "name": null }, { "creator_type": "author", "first_name": "Dominic", "last_name": "Grun", "name": null }, { "creator_type": "author", "first_name": "Julia K.", "last_name": "Lau", "name": null }, { "creator_type": "author", "first_name": "Stephane C.", "last_name": "Boutet", "name": null }, { "creator_type": "author", "first_name": "Chad", "last_name": "Sanada", "name": null }, { "creator_type": "author", "first_name": "Aik", "last_name": "Ooi", "name": null }, { "creator_type": "author", "first_name": "Robert C.", "last_name": "Jones", "name": null }, { "creator_type": "author", "first_name": "Kelly", "last_name": "Kaihara", "name": null }, { "creator_type": "author", "first_name": "Chris", "last_name": "Brampton", "name": null }, { "creator_type": "author", "first_name": "Yasha", "last_name": "Talaga", "name": null }, { "creator_type": "author", "first_name": "Yohei", "last_name": "Sasagawa", "name": null }, { "creator_type": "author", "first_name": "Kaori", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Tetsutaro", "last_name": "Hayashi", "name": null }, { "creator_type": "author", "first_name": "Caroline", "last_name": "Braeuning", "name": null }, { "creator_type": "author", "first_name": "Cornelius", "last_name": "Fischer", "name": null }, { "creator_type": "author", "first_name": "Sascha", "last_name": "Sauer", "name": null }, { "creator_type": "author", "first_name": "Timo", "last_name": "Trefzer", "name": null }, { "creator_type": "author", "first_name": "Christian", "last_name": "Conrad", "name": null }, { "creator_type": "author", "first_name": "Xian", "last_name": "Adiconis", "name": null }, { "creator_type": "author", "first_name": "Lan T.", "last_name": "Nguyen", "name": null }, { "creator_type": "author", "first_name": "Aviv", "last_name": "Regev", "name": null }, { "creator_type": "author", "first_name": "Joshua Z.", "last_name": "Levin", "name": null }, { "creator_type": "author", "first_name": "Swati", "last_name": "Parekh", "name": null }, { "creator_type": "author", "first_name": "Aleksandar", "last_name": "Janjic", "name": null }, { "creator_type": "author", "first_name": "Lucas E.", "last_name": "Wange", "name": null }, { "creator_type": "author", "first_name": "Johannes W.", "last_name": "Bagnoli", "name": null }, { "creator_type": "author", "first_name": "Wolfgang", "last_name": "Enard", "name": null }, { "creator_type": "author", "first_name": "Marta", "last_name": "Gut", "name": null }, { "creator_type": "author", "first_name": "Rickard", "last_name": "Sandberg", "name": null }, { "creator_type": "author", "first_name": "Itoshi", "last_name": "Nikaido", "name": null }, { "creator_type": "author", "first_name": "Ivo", "last_name": "Gut", "name": null }, { "creator_type": "author", "first_name": "Oliver", "last_name": "Stegle", "name": null }, { "creator_type": "author", "first_name": "Holger", "last_name": "Heyn", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41587-020-0469-4" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "32518403" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Benchmarking", "descriptor_ui": "D019985", "major_topic": false }, { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "Databases, Genetic", "descriptor_ui": "D030541", "major_topic": false }, { "descriptor": "Genomics", "descriptor_ui": "D023281", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Sequence Analysis, RNA", "descriptor_ui": "D017423", "major_topic": true }, { "descriptor": "Single-Cell Analysis", "descriptor_ui": "D059010", "major_topic": true } ], "publication": { "conference_name": null, "date": "2020 Jun", "date_precision": "unknown", "issue": "6", "normalized_date": null, "pages": "747-755", "proceedings_title": null, "publisher": "", "title": "Nature biotechnology", "volume": "38", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Benchmarking single-cell RNA-sequencing protocols for cell atlas projects.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "RB1 gene is often homozygously deleted or mutated in prostate adenocarcinomas following acquirement of castration resistance and/or metastatic ability. We found that SUCLA2 gene is frequently involved in the deletion of the RB1 gene region in advanced prostate cancer. SUCLA2 constitutes the beta-subunit of succinate CoA ligase heterodimer that reversibly converts succinyl CoA into succinate. We sought the possibility that deletion of SUCLA2 gives rise to a metabolic vulnerability that could be targeted therapeutically. We found a significant metabolic shift in SUCLA2-deleted prostate cancer cells, including lower mitochondrial respiratory activity. By screening a number of libraries for compounds that induce cell death selectively in SUCLA2-deficient prostate cancer cells, we identified thymoquinone (2-isopropyl-5-methylbenzo-1,4-quinone) and PMA (phorbol-12-myristate-13-acetate) from a natural compound library. These findings indicate that the metabolic vulnerability in SUCLA2-deficient prostate cancer cells is pharmacologically targetable.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Susumu", "last_name": "Kohno", "name": null }, { "creator_type": "author", "first_name": "Paing", "last_name": "Linn", "name": null }, { "creator_type": "author", "first_name": "Naoko", "last_name": "Nagatani", "name": null }, { "creator_type": "author", "first_name": "Yoshihiro", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Sharad", "last_name": "Kumar", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Chiaki", "last_name": "Takahashi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41388-020-1381-6" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "32694611" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Apoptosis", "descriptor_ui": "D017209", "major_topic": false }, { "descriptor": "Benzoquinones", "descriptor_ui": "D016227", "major_topic": false }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Gene Deletion", "descriptor_ui": "D017353", "major_topic": true }, { "descriptor": "HEK293 Cells", "descriptor_ui": "D057809", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Mice, Nude", "descriptor_ui": "D008819", "major_topic": false }, { "descriptor": "Mice, SCID", "descriptor_ui": "D016513", "major_topic": false }, { "descriptor": "PC-3 Cells", "descriptor_ui": "D000078722", "major_topic": false }, { "descriptor": "Prostatic Neoplasms", "descriptor_ui": "D011471", "major_topic": false }, { "descriptor": "Retinoblastoma Protein", "descriptor_ui": "D016160", "major_topic": false }, { "descriptor": "Succinate-CoA Ligases", "descriptor_ui": "D013389", "major_topic": false }, { "descriptor": "Tetradecanoylphorbol Acetate", "descriptor_ui": "D013755", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020 Aug", "date_precision": "unknown", "issue": "34", "normalized_date": null, "pages": "5690-5707", "proceedings_title": null, "publisher": "", "title": "Oncogene", "volume": "39", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Pharmacologically targetable vulnerability in prostate cancer carrying RB1-SUCLA2 deletion.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "OBJECTIVE: Cervical cancer is the fourth most common cause of cancer-related deaths in Asian women, due to its poor prognosis. This study aimed to decipher genomic alteration profiles of a cohort of Japanese cervical cancer patients to understand why certain patients benefited from molecular targeted therapies and their prognostic significance. METHODS: During 2008-2018, 154 cervical cancer patients underwent a potentially curative resection procedure at the National Cancer Center Hospital. Genomic DNA samples were analyzed using Ion AmpliSeq Cancer Hotspot Panel v2. Alterations in the copy number of PIK3CA, ERBB2, PTEN, and STK11 were detected using the TaqMan assay. HPV-positive results were confirmed by genomic testing and in situ hybridization assay. RESULTS: The frequency of genomic alterations in PIK3CA (36%), STK11 (16%), PTEN (11%), TP53 (11%), and KRAS (8%) was >5%. KRAS mutations were preferentially detected in patients with adenocarcinomas, and the frequency of PIK3CA mutations in patients with squamous cell carcinomas was higher than that in patients with other histological cancer types. HPV-positive results were observed in 139/154 (90.3%) patients, and TP53 mutants were detected in HPV-negative specimens. In this study, the overall survival of patients with genomic alterations in STK11 was worse than in patients with wild-type STK11 (hazard ratio = 10.6, P = 0.0079) and TCGA dataset (hazard ratio = 2.46, P = 0.029). CONCLUSIONS: More than one-third of Japanese cervical cancer patients exhibit mutations targeted by molecular targeted therapies. We have proposed the prognostic value of STK11 genomic alterations.", "classifications": [ { "id": "Hamamoto", "label": "Group Hamamoto", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Sou", "last_name": "Hirose", "name": null }, { "creator_type": "author", "first_name": "Naoya", "last_name": "Murakami", "name": null }, { "creator_type": "author", "first_name": "Kazuaki", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Ikumi", "last_name": "Kuno", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Takayanagi", "name": null }, { "creator_type": "author", "first_name": "Yuka", "last_name": "Asami", "name": null }, { "creator_type": "author", "first_name": "Maiko", "last_name": "Matsuda", "name": null }, { "creator_type": "author", "first_name": "Yoko", "last_name": "Shimada", "name": null }, { "creator_type": "author", "first_name": "Shotaro", "last_name": "Yamano", "name": null }, { "creator_type": "author", "first_name": "Kuniko", "last_name": "Sunami", "name": null }, { "creator_type": "author", "first_name": "Kazushi", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Takayuki", "last_name": "Honda", "name": null }, { "creator_type": "author", "first_name": "Tomomi", "last_name": "Nakahara", "name": null }, { "creator_type": "author", "first_name": "Tomoko", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Masaaki", "last_name": "Komatsu", "name": null }, { "creator_type": "author", "first_name": "Ryuji", "last_name": "Hamamoto", "name": null }, { "creator_type": "author", "first_name": "Mayumi Kobayashi", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Matsumoto", "name": null }, { "creator_type": "author", "first_name": "Kae", "last_name": "Okuma", "name": null }, { "creator_type": "author", "first_name": "Takafumi", "last_name": "Kuroda", "name": null }, { "creator_type": "author", "first_name": "Aikou", "last_name": "Okamoto", "name": null }, { "creator_type": "author", "first_name": "Jun", "last_name": "Itami", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Kohno", "name": null }, { "creator_type": "author", "first_name": "Tomoyasu", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Kouya", "last_name": "Shiraishi", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Yoshida", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.ygyno.2019.10.022" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "31757465" } }, "mesh": [ { "descriptor": "AMP-Activated Protein Kinase Kinases", "descriptor_ui": "D000091162", "major_topic": false }, { "descriptor": "Asian People", "descriptor_ui": "D044466", "major_topic": false }, { "descriptor": "DNA Mutational Analysis", "descriptor_ui": "D004252", "major_topic": false }, { "descriptor": "DNA, Neoplasm", "descriptor_ui": "D004273", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Papillomaviridae", "descriptor_ui": "D027383", "major_topic": false }, { "descriptor": "Papillomavirus Infections", "descriptor_ui": "D030361", "major_topic": false }, { "descriptor": "Predictive Value of Tests", "descriptor_ui": "D011237", "major_topic": false }, { "descriptor": "Protein Serine-Threonine Kinases", "descriptor_ui": "D017346", "major_topic": false }, { "descriptor": "Uterine Cervical Neoplasms", "descriptor_ui": "D002583", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020 Jan", "date_precision": "unknown", "issue": "1", "normalized_date": null, "pages": "203-210", "proceedings_title": null, "publisher": "", "title": "Gynecologic oncology", "volume": "156", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Genomic alterations in STK11 can predict clinical outcomes in cervical cancer patients.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "A growing body of evidence suggests that exercise shows pleiotropic effects on the maintenance of systemic homeostasis through mitochondria. Dysregulation of mitochondrial dynamism is associated with metabolic inflexibility, resulting in many of the metabolic diseases and aging. Studies have suggested that exercise prevents and delays the progression of mitochondrial dysfunction by improving mitochondrial metabolism, biogenesis, and quality control. Exercise modulates functions of mitochondrial dynamics-regulating proteins through post-translational modification mechanisms. In this review, we discuss the putative mechanisms underlying maintenance of mitochondrial homeostasis by exercise, especially focusing on the post-translational modifications of several signaling proteins contributing to mitochondrial biogenesis, autophagy or mitophagy flux, and fission/fusion cycle. We also introduce novel small molecules that can potentially mimic exercise therapy through preserving mitochondrial dynamism. These recent advancements in the field of mitochondrial biology may lead to a greater understanding of exercise signaling.", "classifications": [ { "id": "Nishida", "label": "Group Nishida", "parent": "Nishida", "type": "group" }, { "id": "Nishimura", "label": "Group Nishimura", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Tomohiro", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Akiyuki", "last_name": "Nishimura", "name": null }, { "creator_type": "author", "first_name": "Kazuhiro", "last_name": "Nishiyama", "name": null }, { "creator_type": "author", "first_name": "Takumi", "last_name": "Goto", "name": null }, { "creator_type": "author", "first_name": "Takuro", "last_name": "Numaga-Tomita", "name": null }, { "creator_type": "author", "first_name": "Motohiro", "last_name": "Nishida", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/s00424-019-02258-3" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "30707289" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mitochondria, Muscle", "descriptor_ui": "D008931", "major_topic": false }, { "descriptor": "Mitochondrial Dynamics", "descriptor_ui": "D063154", "major_topic": true }, { "descriptor": "Mitophagy", "descriptor_ui": "D063306", "major_topic": false }, { "descriptor": "Motor Activity", "descriptor_ui": "D009043", "major_topic": true } ], "publication": { "conference_name": null, "date": "2020 Feb", "date_precision": "unknown", "issue": "2", "normalized_date": null, "pages": "137-153", "proceedings_title": null, "publisher": "", "title": "Pflugers Archiv : European journal of physiology", "volume": "472", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Mitochondrial dynamics in exercise physiology.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Metabolic reprogramming of leukemia cells is important for survival, proliferation, and drug resistance under conditions of metabolic stress in the bone marrow. Deregulation of cellular metabolism, leading to development of leukemia, occurs through abnormally high expression of transcription factors such as MYC and Ecotropic Virus Integration site 1 protein homolog (EVI1). Overexpression of EVI1 in adults and children with mixed lineage leukemia-rearrangement acute myeloid leukemia (MLL-r AML) has a very poor prognosis. To identify a metabolic inhibitor for EVI1-induced metabolic reprogramming in MLL-r AML, we used an XFp extracellular flux analyzer to examine metabolic changes during leukemia development in mouse models of AML expressing MLL-AF9 and Evi1 (Evi1/MF9). Oxidative phosphorylation (OXPHOS) in Evi1/MF9 AML cells accelerated prior to activation of glycolysis, with a higher dependency on glutamine as an energy source. Furthermore, EVI1 played a role in glycolysis as well as driving production of metabolites in the tricarboxylic acid cycle. L-asparaginase (L-asp) exacerbated growth inhibition induced by glutamine starvation and suppressed OXPHOS and proliferation of Evi1/MF9 both in vitro and in vivo; high sensitivity to L-asp was caused by low expression of asparagine synthetase (ASNS) and L-asp-induced suppression of glutamine metabolism. In addition, samples from patients with EVI1(+)MF9 showed low ASNS expression, suggesting that it is a sensitive marker of L-asp treatment. Clarification of metabolic reprogramming in EVI1(+) leukemia cells may aid development of treatments for EVI1(+)MF9 refractory leukemia.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yusuke", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Sawa", "name": null }, { "creator_type": "author", "first_name": "Mariko", "last_name": "Kinoshita", "name": null }, { "creator_type": "author", "first_name": "Ai", "last_name": "Yamada", "name": null }, { "creator_type": "author", "first_name": "Sachiyo", "last_name": "Kamimura", "name": null }, { "creator_type": "author", "first_name": "Akira", "last_name": "Suekane", "name": null }, { "creator_type": "author", "first_name": "Honami", "last_name": "Ogoh", "name": null }, { "creator_type": "author", "first_name": "Hidemasa", "last_name": "Matsuo", "name": null }, { "creator_type": "author", "first_name": "Souichi", "last_name": "Adachi", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Taga", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Tomizawa", "name": null }, { "creator_type": "author", "first_name": "Motomi", "last_name": "Osato", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Kazuhiro", "last_name": "Morishita", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Moritake", "name": null } ], "identifiers": { "doi": { "normalized": "10.3324/haematol.2019.225953" }, "pmcid": { "normalized": "PMC7395283" }, "pmid": { "normalized": "31649131" } }, "mesh": [ { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Asparaginase", "descriptor_ui": "D001215", "major_topic": false }, { "descriptor": "DNA-Binding Proteins", "descriptor_ui": "D004268", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Leukemia, Myeloid, Acute", "descriptor_ui": "D015470", "major_topic": true }, { "descriptor": "MDS1 and EVI1 Complex Locus Protein", "descriptor_ui": "D000074008", "major_topic": false }, { "descriptor": "Proto-Oncogenes", "descriptor_ui": "D011519", "major_topic": true }, { "descriptor": "Transcription Factors", "descriptor_ui": "D014157", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020 Aug", "date_precision": "unknown", "issue": "8", "normalized_date": null, "pages": "2118-2129", "proceedings_title": null, "publisher": "", "title": "Haematologica", "volume": "105", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "EVI1 triggers metabolic reprogramming associated with leukemogenesis and increases sensitivity to L-asparaginase.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: Epstein-Barr virus (EBV)-positive gastric cancers have clinicopathologic differences from EBV-negative tumors and lack TP53 mutation. Serologic profiles may inform viral contribution to carcinogenesis. METHODS: We compared humoral responses of EBV-positive (n = 67) and EBV-negative (n = 137) patients with gastric cancer from the International EBV-Gastric Cancer Consortium. Serum antibodies against four EBV proteins, nuclear (EBNA), viral capsid (VCA), early-diffuse (EA-D), and Zta replication activator (ZEBRA), and to p53 were assessed by multiplex assays. OR of antibody level tertiles (T1-T3) were adjusted by logistic regression. We also conducted a meta-analysis of reported anti-p53 seropositivity in gastric cancer. RESULTS: Consistent with EBV's ubiquity, 99% of patients were seropositive for anti-EBNA and 98% for anti-VCA, without difference by tumor EBV status. Seropositivity varied between patients with EBV-positive and EBV-negative tumors for anti-EA-D (97% vs. 67%, respectively, P < 0.001) and anti-ZEBRA (97% vs. 85%, respectively, P = 0.009). Adjusted ORs (vs. T1) for patients with EBV-positive versus EBV-negative tumors were significantly elevated for higher antibodies against EBNA (2.6 for T2 and 13 for T3), VCA (1.8 for T2 and 2.4 for T3), EA-D (6.0 for T2 and 44 for T3), and ZEBRA (4.6 for T2 and 12 for T3). Antibodies to p53 were inversely associated with EBV positivity (3% vs. 15%; adjusted OR = 0.16, P = 0.021). Anti-p53 prevalence from the literature was 15%. CONCLUSIONS: These serologic patterns suggest viral reactivation in EBV-positive cancers and identify variation of p53 seropositivity by subtype. IMPACT: Anti-EBV and anti-p53 antibodies are differentially associated with tumor EBV positivity. Serology may identify EBV-positive gastric cancer for targeted therapies.", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "M. Constanza", "last_name": "Camargo", "name": null }, { "creator_type": "author", "first_name": "Kyoung-Mee", "last_name": "Kim", "name": null }, { "creator_type": "author", "first_name": "Keitaro", "last_name": "Matsuo", "name": null }, { "creator_type": "author", "first_name": "Javier", "last_name": "Torres", "name": null }, { "creator_type": "author", "first_name": "Linda M.", "last_name": "Liao", "name": null }, { "creator_type": "author", "first_name": "Douglas", "last_name": "Morgan", "name": null }, { "creator_type": "author", "first_name": "Angelika", "last_name": "Michel", "name": null }, { "creator_type": "author", "first_name": "Tim", "last_name": "Waterboer", "name": null }, { "creator_type": "author", "first_name": "Minkyo", "last_name": "Song", "name": null }, { "creator_type": "author", "first_name": "Margaret L.", "last_name": "Gulley", "name": null }, { "creator_type": "author", "first_name": "Ricardo L.", "last_name": "Dominguez", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null }, { "creator_type": "author", "first_name": "Sung", "last_name": "Kim", "name": null }, { "creator_type": "author", "first_name": "Gustavo", "last_name": "Cortes-Martinez", "name": null }, { "creator_type": "author", "first_name": "Jolanta", "last_name": "Lissowska", "name": null }, { "creator_type": "author", "first_name": "Jovanny", "last_name": "Zabaleta", "name": null }, { "creator_type": "author", "first_name": "Michael", "last_name": "Pawlita", "name": null }, { "creator_type": "author", "first_name": "Charles S.", "last_name": "Rabkin", "name": null } ], "identifiers": { "doi": { "normalized": "10.1158/1055-9965.epi-19-0790" }, "pmcid": { "normalized": "PMC8272980" }, "pmid": { "normalized": "31719065" } }, "mesh": [ { "descriptor": "Antibodies, Viral", "descriptor_ui": "D000914", "major_topic": false }, { "descriptor": "Capsid", "descriptor_ui": "D002213", "major_topic": false }, { "descriptor": "Carcinogenesis", "descriptor_ui": "D063646", "major_topic": false }, { "descriptor": "Epstein-Barr Virus Infections", "descriptor_ui": "D020031", "major_topic": false }, { "descriptor": "Epstein-Barr Virus Nuclear Antigens", "descriptor_ui": "D019309", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Herpesvirus 4, Human", "descriptor_ui": "D004854", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Serologic Tests", "descriptor_ui": "D012698", "major_topic": false }, { "descriptor": "Stomach Neoplasms", "descriptor_ui": "D013274", "major_topic": false }, { "descriptor": "Tumor Suppressor Protein p53", "descriptor_ui": "D016159", "major_topic": false }, { "descriptor": "Virus Activation", "descriptor_ui": "D014775", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020 Feb", "date_precision": "unknown", "issue": "2", "normalized_date": null, "pages": "414-419", "proceedings_title": null, "publisher": "", "title": "Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology", "volume": "29", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Circulating Antibodies against Epstein-Barr Virus (EBV) and p53 in EBV-Positive and -Negative Gastric Cancer.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Stomata are tiny pores on plant leaves and stems surrounded by a pair of differentiated epidermal cells known as guard cells. Plants undergo guard cell differentiation in response to environmental cues, including atmospheric CO(2) . To quantitatively evaluate stomatal development in response to elevated CO(2) , imaging analysis of stomata was conducted using young cotyledons of Arabidopsis thaliana grown under ambient (380 ppm) and elevated (1,000 ppm) CO(2) conditions. Our analysis revealed that treatment with 1,000 ppm CO(2) did not affect stomatal numbers on abaxial sides of cotyledons but increased cotyledon area, resulting in decreased stomatal density, 7 days after germination. Interestingly, this treatment also perturbed the uniform distribution of stomata via excess satellite stomata and stomatal precursor cells. We used overexpression lines of the DNA replication licensing factor gene CDC6, a reported positive regulator of satellite stomata production. CDC6 overexpression decreased the speed of cotyledon expansion, even under treatment with 1,000 ppm CO(2) , possibly by suppressing pavement cell maturation. In contrast, treatment with 1,000 ppm CO(2) induced stomatal distribution changes in the overexpressor. These results suggest that treatment with 1,000 ppm CO(2) enhances both cotyledon expansion and satellite stomata production via independent pathways, at least in young cotyledons of A. thaliana.", "classifications": [ { "id": "Higaki", "label": "Group Higaki", "parent": "Ueda", "type": "group" }, { "id": "Ueda", "label": "Team Ueda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Takumi", "last_name": "Higaki", "name": null }, { "creator_type": "author", "first_name": "Kae", "last_name": "Akita", "name": null }, { "creator_type": "author", "first_name": "Seiichiro", "last_name": "Hasezawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/gtc.12773" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "32294311" } }, "mesh": [ { "descriptor": "Arabidopsis", "descriptor_ui": "D017360", "major_topic": false }, { "descriptor": "Arabidopsis Proteins", "descriptor_ui": "D029681", "major_topic": false }, { "descriptor": "Carbon Dioxide", "descriptor_ui": "D002245", "major_topic": false }, { "descriptor": "Cell Cycle Proteins", "descriptor_ui": "D018797", "major_topic": false }, { "descriptor": "Cotyledon", "descriptor_ui": "D018548", "major_topic": false }, { "descriptor": "Gene Expression Regulation, Plant", "descriptor_ui": "D018506", "major_topic": false }, { "descriptor": "Plant Stomata", "descriptor_ui": "D054046", "major_topic": false }, { "descriptor": "Plants, Genetically Modified", "descriptor_ui": "D030821", "major_topic": false }, { "descriptor": "Up-Regulation", "descriptor_ui": "D015854", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020 Jul", "date_precision": "unknown", "issue": "7", "normalized_date": null, "pages": "475-482", "proceedings_title": null, "publisher": "", "title": "Genes to cells : devoted to molecular & cellular mechanisms", "volume": "25", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Elevated CO(2) promotes satellite stomata production in young cotyledons of Arabidopsis thaliana.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "An amendment to this paper has been published and can be accessed via a link at the top of the paper.", "classifications": [ { "id": "Yusa", "label": "Group Yusa", "parent": "Eiraku", "type": "group" }, { "id": "Eiraku", "label": "Team Eiraku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Sankari", "last_name": "Nagarajan", "name": null }, { "creator_type": "author", "first_name": "Shalini V.", "last_name": "Rao", "name": null }, { "creator_type": "author", "first_name": "Joseph", "last_name": "Sutton", "name": null }, { "creator_type": "author", "first_name": "Danya", "last_name": "Cheeseman", "name": null }, { "creator_type": "author", "first_name": "Shanade", "last_name": "Dunn", "name": null }, { "creator_type": "author", "first_name": "Evangelia K.", "last_name": "Papachristou", "name": null }, { "creator_type": "author", "first_name": "Jose-Enrique Gonzalez", "last_name": "Prada", "name": null }, { "creator_type": "author", "first_name": "Dominique-Laurent", "last_name": "Couturier", "name": null }, { "creator_type": "author", "first_name": "Sanjeev", "last_name": "Kumar", "name": null }, { "creator_type": "author", "first_name": "Kamal", "last_name": "Kishore", "name": null }, { "creator_type": "author", "first_name": "Chandra Sekhar Reddy", "last_name": "Chilamakuri", "name": null }, { "creator_type": "author", "first_name": "Silvia-Elena", "last_name": "Glont", "name": null }, { "creator_type": "author", "first_name": "Emily Archer", "last_name": "Goode", "name": null }, { "creator_type": "author", "first_name": "Cara", "last_name": "Brodie", "name": null }, { "creator_type": "author", "first_name": "Naomi", "last_name": "Guppy", "name": null }, { "creator_type": "author", "first_name": "Rachael", "last_name": "Natrajan", "name": null }, { "creator_type": "author", "first_name": "Alejandra", "last_name": "Bruna", "name": null }, { "creator_type": "author", "first_name": "Carlos", "last_name": "Caldas", "name": null }, { "creator_type": "author", "first_name": "Alasdair", "last_name": "Russell", "name": null }, { "creator_type": "author", "first_name": "Rasmus", "last_name": "Siersbaek", "name": null }, { "creator_type": "author", "first_name": "Kosuke", "last_name": "Yusa", "name": null }, { "creator_type": "author", "first_name": "Igor", "last_name": "Chernukhin", "name": null }, { "creator_type": "author", "first_name": "Jason S.", "last_name": "Carroll", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41588-020-0582-9" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "32005967" } }, "mesh": [], "publication": { "conference_name": null, "date": "2020 Mar", "date_precision": "unknown", "issue": "3", "normalized_date": null, "pages": "354", "proceedings_title": null, "publisher": "", "title": "Nature genetics", "volume": "52", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Author Correction: ARID1A influences HDAC1/BRD4 activity, intrinsic proliferative capacity and breast cancer treatment response.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Cysteine persulfide (CysSSH) and cysteine polysulfides (CysSSnH, n > 1) are cysteine derivatives that have sulfane sulfur atoms bound to cysteine thiol. Advances in analytical methods that detect and quantify persulfides and polysulfides have shown that CysSSH and related species such as glutathione persulfide occur physiologically and are prevalent in prokaryotes, eukaryotes, and mammals in vivo. The chemical properties and abundance of these compounds suggest a central role for reactive persulfides in cell-regulatory processes. CysSSH and related species have been suggested to act as powerful antioxidants and cellular protectants and may serve as redox signaling intermediates. It was recently shown that cysteinyl-tRNA synthetase (CARS) is a new cysteine persulfide synthase. In addition, we discovered that CARS is involved in protein polysulfidation that is coupled with translation. Mitochondrial activity in biogenesis and bioenergetics is supported and upregulated by CysSSH derived from mitochondrial CARS. In this review article, we discuss the mechanisms of the biosynthesis of CysSSH and related persulfide species, with a particular focus on the roles of CARS. We also review the antioxidative and anti-inflammatory actions of persulfides.", "classifications": [ { "id": "Akaike", "label": "Group Akaike", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Tomohiro", "last_name": "Sawa", "name": null }, { "creator_type": "author", "first_name": "Hozumi", "last_name": "Motohashi", "name": null }, { "creator_type": "author", "first_name": "Hideshi", "last_name": "Ihara", "name": null }, { "creator_type": "author", "first_name": "Takaaki", "last_name": "Akaike", "name": null } ], "identifiers": { "doi": { "normalized": "10.3390/biom10091245" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "32867265" } }, "mesh": [ { "descriptor": "Amino Acyl-tRNA Synthetases", "descriptor_ui": "D000604", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Anti-Inflammatory Agents, Non-Steroidal", "descriptor_ui": "D000894", "major_topic": false }, { "descriptor": "Antioxidants", "descriptor_ui": "D000975", "major_topic": false }, { "descriptor": "Cysteine", "descriptor_ui": "D003545", "major_topic": false }, { "descriptor": "Disulfides", "descriptor_ui": "D004220", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Sulfides", "descriptor_ui": "D013440", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020 Sep", "date_precision": "unknown", "issue": "9", "normalized_date": null, "pages": "", "proceedings_title": null, "publisher": "", "title": "Biomolecules", "volume": "10", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Enzymatic Regulation and Biological Functions of Reactive Cysteine Persulfides and Polysulfides.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The heart flexibly changes its structure in response to changing environments and oxygen/nutrition demands of the body. Increased and decreased mechanical loading induces hypertrophy and atrophy of cardiomyocytes, respectively. In physiological conditions, these structural changes of the heart are reversible. However, chronic stresses such as hypertension or cancer cachexia cause irreversible remodeling of the heart, leading to heart failure. Accumulating evidence indicates that calcium dyshomeostasis and aberrant reactive oxygen species production cause pathological heart remodeling. Canonical transient receptor potential (TRPC) is a nonselective cation channel subfamily whose multimodal activation or modulation of channel activity play important roles in a plethora of cellular physiology. Roles of TRPC channels in cardiac physiology have been reported in pathological cardiac remodeling. In this review, we summarize recent findings regarding the importance of TRPC channels in flexible cardiac remodeling (i.e., cardiac plasticity) in response to environmental stresses and discuss questions that should be addressed in the near future.", "classifications": [ { "id": "Nishida", "label": "Group Nishida", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Takuro", "last_name": "Numaga-Tomita", "name": null }, { "creator_type": "author", "first_name": "Motohiro", "last_name": "Nishida", "name": null } ], "identifiers": { "doi": { "normalized": "10.3390/cells9020454" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "32079284" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Calcium", "descriptor_ui": "D002118", "major_topic": false }, { "descriptor": "Disease Models, Animal", "descriptor_ui": "D004195", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Myocytes, Cardiac", "descriptor_ui": "D032383", "major_topic": false }, { "descriptor": "Transient Receptor Potential Channels", "descriptor_ui": "D050051", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020 Feb", "date_precision": "unknown", "issue": "2", "normalized_date": null, "pages": "", "proceedings_title": null, "publisher": "", "title": "Cells", "volume": "9", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "TRPC Channels in Cardiac Plasticity.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Dry-cured ham with a long ripening period is a valuable product worldwide. Ripening time is a key determinant of the endogenous metabolites that characterize the flavor and taste of ham products. While various studies have analyzed the relationship between ripening duration and sensory characteristics, no studies have evaluated ham products produced in Japan. Here, we conducted time-course metabolomic profiling, taste sensor-based analyses, and sensory evaluations by non-trained consumers during ripening. Capillary electrophoresis-mass spectrometry was used to quantify non-volatile metabolites, such as amino acids, organic acids, and nucleotides. In an analysis of eight time-points during 680 days of ripening, the highest score for the after-taste of umami was observed on day 540, despite subtle changes in the scores for other properties. The concentrations of aspartic acid and glutamic acid relative to those of total amino acids were the highest at this point. This approach can contribute to the understanding of the relationship between the metabolite profile and ripening duration.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Masahiro", "last_name": "Sugimoto", "name": null }, { "creator_type": "author", "first_name": "Tetsuya", "last_name": "Sugawara", "name": null }, { "creator_type": "author", "first_name": "Shinichi", "last_name": "Obiya", "name": null }, { "creator_type": "author", "first_name": "Ayame", "last_name": "Enomoto", "name": null }, { "creator_type": "author", "first_name": "Miku", "last_name": "Kaneko", "name": null }, { "creator_type": "author", "first_name": "Sana", "last_name": "Ota", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Masaru", "last_name": "Tomita", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.foodres.2019.108850" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "32036920" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Food Handling", "descriptor_ui": "D005511", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Meat Products", "descriptor_ui": "D008461", "major_topic": false }, { "descriptor": "Pork Meat", "descriptor_ui": "D000080305", "major_topic": false }, { "descriptor": "Sensation", "descriptor_ui": "D012677", "major_topic": true }, { "descriptor": "Swine", "descriptor_ui": "D013552", "major_topic": false }, { "descriptor": "Taste", "descriptor_ui": "D013649", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020 Mar", "date_precision": "unknown", "issue": "", "normalized_date": null, "pages": "108850", "proceedings_title": null, "publisher": "", "title": "Food research international (Ottawa, Ont.)", "volume": "129", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Sensory properties and metabolomic profiles of dry-cured ham during the ripening process.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Exposure of the brain to high levels of glucocorticoids during ischemia-reperfusion induces neuronal cell death. Oxidative stress alters blood-brain barrier (BBB) function during ischemia-reperfusion, and so we hypothesized that it might impair P-glycoprotein (P-gp)-mediated efflux transport of glucocorticoids at the BBB. Therefore, the purpose of this study was to clarify the molecular mechanism of this putative decrease of P-gp-mediated efflux function. First, we established that H(2)O(2) treatment of a human in vitro BBB model (hCMEC/D3) reduced both P-gp efflux transport activity and protein expression on the plasma membrane within 20 min. These results suggested that the rapid decrease of efflux function might be due to internalization of P-gp. Furthermore, H(2)O(2) treatment markedly increased tyrosine-14-phosphorylated caveolin-1, which is involved in P-gp internalization. A brain perfusion study in rats showed that cortisol efflux at the BBB was markedly decreased by H(2)O(2) administration, and inhibitors of Abl kinase and Src kinase, which phosphorylate tyrosine-14 in caveolin-1, suppressed this decrease. Overall, these findings support the idea that oxidative stress-induced activation of Abl kinase and Src kinase induces internalization of P-gp via the phosphorylation of tyrosine-14 in caveolin-1, leading to a rapid decrease of P-gp-mediated cortisol efflux at the BBB.", "classifications": [ { "id": "Suzuki", "label": "Group Suzuki", "parent": "Takekawa", "type": "group" }, { "id": "Takekawa", "label": "Team Takekawa", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yutaro", "last_name": "Hoshi", "name": null }, { "creator_type": "author", "first_name": "Yasuo", "last_name": "Uchida", "name": null }, { "creator_type": "author", "first_name": "Masanori", "last_name": "Tachikawa", "name": null }, { "creator_type": "author", "first_name": "Sumio", "last_name": "Ohtsuki", "name": null }, { "creator_type": "author", "first_name": "Pierre-Olivier", "last_name": "Couraud", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Tetsuya", "last_name": "Terasaki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1177/0271678x18822801" }, "pmcid": { "normalized": "PMC7370610" }, "pmid": { "normalized": "30621530" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "ATP Binding Cassette Transporter, Subfamily B", "descriptor_ui": "D018435", "major_topic": false }, { "descriptor": "Blood-Brain Barrier", "descriptor_ui": "D001812", "major_topic": false }, { "descriptor": "Caveolin 1", "descriptor_ui": "D051242", "major_topic": false }, { "descriptor": "CSK Tyrosine-Protein Kinase", "descriptor_ui": "D000081247", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Hydrocortisone", "descriptor_ui": "D006854", "major_topic": false }, { "descriptor": "Hydrogen Peroxide", "descriptor_ui": "D006861", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Oxidative Stress", "descriptor_ui": "D018384", "major_topic": true }, { "descriptor": "Phosphorylation", "descriptor_ui": "D010766", "major_topic": false }, { "descriptor": "Proto-Oncogene Proteins c-abl", "descriptor_ui": "D016315", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Rats, Sprague-Dawley", "descriptor_ui": "D017207", "major_topic": false } ], "publication": { "conference_name": null, "date": "2020 Feb", "date_precision": "unknown", "issue": "2", "normalized_date": null, "pages": "420-436", "proceedings_title": null, "publisher": "", "title": "Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism", "volume": "40", "year": 2020 }, "ssbd": { "database": [], "repository": [] }, "title": "Oxidative stress-induced activation of Abl and Src kinases rapidly induces P-glycoprotein internalization via phosphorylation of caveolin-1 on tyrosine-14, decreasing cortisol efflux at the blood-brain barrier.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: A previous dasatinib discontinuation (DADI) trial showed that 31 (49%) of 63 patients with chronic-phase chronic myeloid leukaemia who were treated with second-line or subsequent dasatinib could discontinue the drug safely. However, the safety and efficacy of discontinuing first-line dasatinib remains unclear. In this trial (the first-line DADI trial) we aimed to assess molecular relapse-free survival at 6 months after discontinuation of dasatinib in patients with chronic myeloid leukaemia who had been treated with first-line dasatinib and had maintained deep molecular response for at least 1 year. METHODS: The first-line DADI trial was a single-arm, multicentre, phase 2 trial done at 23 hospitals in Japan. Patients with newly diagnosed chronic-phase chronic myeloid leukaemia without hepatosplenomegaly and extramedullary mass, who received at least 24-month dasatinib treatment and had a sustained deep molecular response (defined as BCR-ABL1/ABL1 international scale 350 anti-cancer drugs and CRISPR-Cas9 loss-of-fitness effects. Established clinically-relevant fusions were identified. Overall, detection of functional fusions was rare, including those involving cancer driver genes, suggesting that many fusions are dispensable for tumour fitness. Therapeutically actionable fusions involving RAF1, BRD4 and ROS1 were verified in new histologies. In addition, recurrent YAP1-MAML2 fusions were identified as activators of Hippo-pathway signaling in multiple cancer types. Our approach discriminates functional fusions, identifying new drivers of carcinogenesis and fusions that could have clinical implications.", "classifications": [ { "id": "Yusa", "label": "Group Yusa", "parent": "Eiraku", "type": "group" }, { "id": "Eiraku", "label": "Team Eiraku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Gabriele", "last_name": "Picco", "name": null }, { "creator_type": "author", "first_name": "Elisabeth D.", "last_name": "Chen", "name": null }, { "creator_type": "author", "first_name": "Luz Garcia", "last_name": "Alonso", "name": null }, { "creator_type": "author", "first_name": "Fiona M.", "last_name": "Behan", "name": null }, { "creator_type": "author", "first_name": "Emanuel", "last_name": "Goncalves", "name": null }, { "creator_type": "author", "first_name": "Graham", "last_name": "Bignell", "name": null }, { "creator_type": "author", "first_name": "Angela", "last_name": "Matchan", "name": null }, { "creator_type": "author", "first_name": "Beiyuan", "last_name": "Fu", "name": null }, { "creator_type": "author", "first_name": "Ruby", "last_name": "Banerjee", "name": null }, { "creator_type": "author", "first_name": "Elizabeth", "last_name": "Anderson", "name": null }, { "creator_type": "author", "first_name": "Adam", "last_name": "Butler", "name": null }, { "creator_type": "author", "first_name": "Cyril H.", "last_name": "Benes", "name": null }, { "creator_type": "author", "first_name": "Ultan", "last_name": "McDermott", "name": null }, { "creator_type": "author", "first_name": "David", "last_name": "Dow", "name": null }, { "creator_type": "author", "first_name": "Francesco", "last_name": "Iorio", "name": null }, { "creator_type": "author", "first_name": "Euan", "last_name": "Stronach", "name": null }, { "creator_type": "author", "first_name": "Fengtang", "last_name": "Yang", "name": null }, { "creator_type": "author", "first_name": "Kosuke", "last_name": "Yusa", "name": null }, { "creator_type": "author", "first_name": "Julio", "last_name": "Saez-Rodriguez", "name": null }, { "creator_type": "author", "first_name": "Mathew J.", "last_name": "Garnett", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41467-019-09940-1" }, "pmcid": { "normalized": "PMC6522557" }, "pmid": { "normalized": "31097696" } }, "mesh": [ { "descriptor": "Antineoplastic Agents", "descriptor_ui": "D000970", "major_topic": false }, { "descriptor": "Biomarkers, Tumor", "descriptor_ui": "D014408", "major_topic": false }, { "descriptor": "Carcinogenesis", "descriptor_ui": "D063646", "major_topic": false }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "CRISPR-Cas Systems", "descriptor_ui": "D064113", "major_topic": false }, { "descriptor": "Datasets as Topic", "descriptor_ui": "D066264", "major_topic": false }, { "descriptor": "Drug Resistance, Neoplasm", "descriptor_ui": "D019008", "major_topic": false }, { "descriptor": "Early Detection of Cancer", "descriptor_ui": "D055088", "major_topic": false }, { "descriptor": "Gene Expression Profiling", "descriptor_ui": "D020869", "major_topic": false }, { "descriptor": "Gene Expression Regulation, Neoplastic", "descriptor_ui": "D015972", "major_topic": false }, { "descriptor": "Gene Fusion", "descriptor_ui": "D050939", "major_topic": false }, { "descriptor": "Genomics", "descriptor_ui": "D023281", "major_topic": false }, { "descriptor": "High-Throughput Nucleotide Sequencing", "descriptor_ui": "D059014", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Neoplasms", "descriptor_ui": "D009369", "major_topic": false }, { "descriptor": "Sequence Analysis, RNA", "descriptor_ui": "D017423", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019 May 16", "date_precision": "day", "issue": "1", "normalized_date": "2019-05-16", "pages": "2198", "proceedings_title": null, "publisher": "", "title": "Nature communications", "volume": "10", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "Functional linkage of gene fusions to cancer cell fitness assessed by pharmacological and CRISPR-Cas9 screening.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: Wolf-Hirschhorn syndrome candidate gene-1 (WHSC1), a histone methyltransferase, has been found to be upregulated and its expression to be correlated with expression of enhancer of zeste homolog 2 (EZH2) in several cancers. In this study, we evaluated the role of WHSC1 and its therapeutic significance in ovarian clear cell carcinoma (OCCC). METHODS: First, we analyzed WHSC1 expression by quantitative PCR and immunohistochemistry using 23 clinical OCCC specimens. Second, the involvement of WHSC1 in OCCC cell proliferation was evaluated by MTT assays after siRNA-mediated WHSC1 knockdown. We also performed flow cytometry (FACS) to address the effect of WHSC1 on cell cycle. To examine the functional relationship between EZH2 and WHSC1, we knocked down EZH2 using siRNAs and checked the expression levels of WHSC1 and its histone mark H3K36m2 in OCCC cell lines. Finally, we checked WHSC1 expression after treatment with the selective inhibitor, GSK126. RESULTS: Both quantitative PCR and immunohistochemical analysis revealed that WHSC1 was significantly overexpressed in OCCC tissues compared with that in normal ovarian tissues. MTT assay revealed that knockdown of WHSC1 suppressed cell proliferation, and H3K36me2 levels were found to be decreased in immunoblotting. FACS revealed that WHSC1 knockdown affected the cell cycle. We also confirmed that WHSC1 expression was suppressed by EZH2 knockdown or inhibition, indicating that EZH2 is upstream of WHSC1 in OCCC cells. CONCLUSIONS: WHSC1 overexpression induced cell growth and its expression is, at least in part, regulated by EZH2. Further functional analysis will reveal whether WHSC1 is a promising therapeutic target for OCCC.", "classifications": [ { "id": "Hamamoto", "label": "Group Hamamoto", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Machiko", "last_name": "Kojima", "name": null }, { "creator_type": "author", "first_name": "Kenbun", "last_name": "Sone", "name": null }, { "creator_type": "author", "first_name": "Katsutoshi", "last_name": "Oda", "name": null }, { "creator_type": "author", "first_name": "Ryuji", "last_name": "Hamamoto", "name": null }, { "creator_type": "author", "first_name": "Syuzo", "last_name": "Kaneko", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Oki", "name": null }, { "creator_type": "author", "first_name": "Asako", "last_name": "Kukita", "name": null }, { "creator_type": "author", "first_name": "Hidenori", "last_name": "Machino", "name": null }, { "creator_type": "author", "first_name": "Harunori", "last_name": "Honjoh", "name": null }, { "creator_type": "author", "first_name": "Yoshiko", "last_name": "Kawata", "name": null }, { "creator_type": "author", "first_name": "Tomoko", "last_name": "Kashiyama", "name": null }, { "creator_type": "author", "first_name": "Kayo", "last_name": "Asada", "name": null }, { "creator_type": "author", "first_name": "Michihiro", "last_name": "Tanikawa", "name": null }, { "creator_type": "author", "first_name": "Mayuyo", "last_name": "Mori-Uchino", "name": null }, { "creator_type": "author", "first_name": "Tetsushi", "last_name": "Tsuruga", "name": null }, { "creator_type": "author", "first_name": "Kazunori", "last_name": "Nagasaka", "name": null }, { "creator_type": "author", "first_name": "Yoko", "last_name": "Matsumoto", "name": null }, { "creator_type": "author", "first_name": "Osamu", "last_name": "Wada-Hiraike", "name": null }, { "creator_type": "author", "first_name": "Yutaka", "last_name": "Osuga", "name": null }, { "creator_type": "author", "first_name": "Tomoyuki", "last_name": "Fujii", "name": null } ], "identifiers": { "doi": { "normalized": "10.1186/s12885-019-5638-9" }, "pmcid": { "normalized": "PMC6521555" }, "pmid": { "normalized": "31092221" } }, "mesh": [ { "descriptor": "Adenocarcinoma, Clear Cell", "descriptor_ui": "D018262", "major_topic": false }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Cell Proliferation", "descriptor_ui": "D049109", "major_topic": false }, { "descriptor": "Enhancer of Zeste Homolog 2 Protein", "descriptor_ui": "D000071221", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Gene Expression Regulation, Neoplastic", "descriptor_ui": "D015972", "major_topic": false }, { "descriptor": "Gene Knockdown Techniques", "descriptor_ui": "D055785", "major_topic": false }, { "descriptor": "Histone-Lysine N-Methyltransferase", "descriptor_ui": "D011495", "major_topic": false }, { "descriptor": "Histones", "descriptor_ui": "D006657", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Ovarian Neoplasms", "descriptor_ui": "D010051", "major_topic": false }, { "descriptor": "Repressor Proteins", "descriptor_ui": "D012097", "major_topic": false }, { "descriptor": "Up-Regulation", "descriptor_ui": "D015854", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019 May 15", "date_precision": "day", "issue": "1", "normalized_date": "2019-05-15", "pages": "455", "proceedings_title": null, "publisher": "", "title": "BMC cancer", "volume": "19", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "The histone methyltransferase WHSC1 is regulated by EZH2 and is important for ovarian clear cell carcinoma cell proliferation.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Neurons of the parabrachial nucleus (PB) receive nociceptive input from the dorsal horn (DH) of the spinal cord and caudal part of the spinal trigeminal nucleus (Vc). Previously, we demonstrated that glutamatergic lateral PB neurons innervate orexin (ORX) neurons in the perifornical area (PeF) of the hypothalamus. However, the neural circuit via which ORX neurons receive nociceptive input from the DH and brainstem remains to be determined. In the present study, we aimed to clarify the potential nociceptive circuit from DH/Vc to PeF via lateral PB. We first examined the neuronal activity of fluorogold (FG)-labeled, PeF-projecting lateral PB neurons in Wistar rats following either saline or formalin injection to the forepaw or lips. We clearly detected more abundant c-Fos-positive, FG-labeled neurons in the PB nucleus. To investigate the relay from the DH/Vc to the PeF via the lateral PB, we injected FG into the PeF and biotinylated dextranamine (BDA) into the contralateral DH or ipsilateral Vc. We observed the most prominent overlap between BDA-labeled axon terminals and FG-labeled neurons in the dorsal lateral and central lateral subnuclei. Furthermore, we found that FG-labeled neurons formed close contact sites with BDA-labeled axons with synaptophysin immunoreactivity. Using electron microscopy, we confirmed that these contact sites were truly synapses. Taken together, our results indicate that the DH/Vc transmits nociceptive information to the PeF via the lateral PB, suggesting the involvement of ORX neurons in the pain pathway.", "classifications": [ { "id": "Yokota", "label": "Group Yokota", "parent": "Enomoto", "type": "group" }, { "id": "Enomoto", "label": "Team Enomoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Hirohiko", "last_name": "Asano", "name": null }, { "creator_type": "author", "first_name": "Yosuke", "last_name": "Arima", "name": null }, { "creator_type": "author", "first_name": "Shigefumi", "last_name": "Yokota", "name": null }, { "creator_type": "author", "first_name": "Masashi", "last_name": "Fujitani", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.bbrc.2019.02.153" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "30922564" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Hypothalamus", "descriptor_ui": "D007031", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Nerve Net", "descriptor_ui": "D009415", "major_topic": false }, { "descriptor": "Neural Pathways", "descriptor_ui": "D009434", "major_topic": true }, { "descriptor": "Nociceptors", "descriptor_ui": "D009619", "major_topic": false }, { "descriptor": "Parabrachial Nucleus", "descriptor_ui": "D065823", "major_topic": false }, { "descriptor": "Rats, Wistar", "descriptor_ui": "D017208", "major_topic": false }, { "descriptor": "Spinal Cord", "descriptor_ui": "D013116", "major_topic": false }, { "descriptor": "Trigeminal Nucleus, Spinal", "descriptor_ui": "D014279", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019 May 14", "date_precision": "day", "issue": "4", "normalized_date": "2019-05-14", "pages": "705-711", "proceedings_title": null, "publisher": "", "title": "Biochemical and biophysical research communications", "volume": "512", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "New nociceptive circuits to the hypothalamic perifornical area from the spinal cord and spinal trigeminal nucleus via the parabrachial nucleus.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "CpG islands (CGIs) including those at imprinting control regions (ICRs) are protected from de novo methylation in somatic cells. However, many cancers often exhibit CGI hypermethylation, implying that the machinery is impaired in cancer cells. Here, we conducted a comprehensive analysis of CGI methylation during somatic cell reprogramming. Although most CGIs remain hypomethylated, a small subset of CGIs, particularly at several ICRs, was often de novo methylated in reprogrammed pluripotent stem cells (PSCs). Such de novo ICR methylation was linked with the silencing of reprogramming factors, which occurs at a late stage of reprogramming. The ICR-preferred CGI hypermethylation was similarly observed in human PSCs. Mechanistically, ablation of Dnmt3a prevented PSCs from de novo ICR methylation. Notably, the ICR-preferred CGI hypermethylation was observed in pediatric cancers, while adult cancers exhibit genome-wide CGI hypermethylation. These results may have important implications in the pathogenesis of pediatric cancers and the application of PSCs.", "classifications": [ { "id": "Yamamoto", "label": "Group Yamamoto", "parent": "Toyoshima", "type": "group" }, { "id": "Toyoshima", "label": "Team Toyoshima", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Masaki", "last_name": "Yagi", "name": null }, { "creator_type": "author", "first_name": "Mio", "last_name": "Kabata", "name": null }, { "creator_type": "author", "first_name": "Tomoyo", "last_name": "Ukai", "name": null }, { "creator_type": "author", "first_name": "Sho", "last_name": "Ohta", "name": null }, { "creator_type": "author", "first_name": "Akito", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Yui", "last_name": "Shimada", "name": null }, { "creator_type": "author", "first_name": "Michihiko", "last_name": "Sugimoto", "name": null }, { "creator_type": "author", "first_name": "Kimi", "last_name": "Araki", "name": null }, { "creator_type": "author", "first_name": "Keisuke", "last_name": "Okita", "name": null }, { "creator_type": "author", "first_name": "Knut", "last_name": "Woltjen", "name": null }, { "creator_type": "author", "first_name": "Konrad", "last_name": "Hochedlinger", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Yasuhiro", "last_name": "Yamada", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.stemcr.2019.04.008" }, "pmcid": { "normalized": "PMC6524733" }, "pmid": { "normalized": "31056481" } }, "mesh": [ { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Cellular Reprogramming", "descriptor_ui": "D065150", "major_topic": false }, { "descriptor": "CpG Islands", "descriptor_ui": "D018899", "major_topic": false }, { "descriptor": "DNA Methylation", "descriptor_ui": "D019175", "major_topic": false }, { "descriptor": "Epigenesis, Genetic", "descriptor_ui": "D044127", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Genomic Imprinting", "descriptor_ui": "D018392", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Induced Pluripotent Stem Cells", "descriptor_ui": "D057026", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice, 129 Strain", "descriptor_ui": "D057507", "major_topic": false }, { "descriptor": "Mice, Inbred ICR", "descriptor_ui": "D008813", "major_topic": false }, { "descriptor": "Pluripotent Stem Cells", "descriptor_ui": "D039904", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019 May 14", "date_precision": "day", "issue": "5", "normalized_date": "2019-05-14", "pages": "1113-1128", "proceedings_title": null, "publisher": "", "title": "Stem cell reports", "volume": "12", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "De Novo DNA Methylation at Imprinted Loci during Reprogramming into Naive and Primed Pluripotency.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Olfaction guides goal-directed behaviours including feeding. To investigate how central olfactory neural circuits control feeding behaviour in mice, we performed retrograde tracing from the lateral hypothalamus (LH), an important feeding centre. We observed a cluster of retrogradely labelled cells distributed in the posteroventral region of the olfactory peduncle. Histochemical analyses revealed that the majority of these retrogradely labelled projection neurons expressed glutamic acid decarboxylase 65/67 (GAD65/67), but not vesicular glutamate transporter 1 (VGluT1). We named this region containing GABAergic projection neurons the ventral olfactory nucleus (VON) to differentiate it from the conventional olfactory peduncle. VON neurons were less immunoreactive for DARPP-32, a striatal neuron marker, compared to neurons in the olfactory tubercle and nucleus accumbens, which distinguished the VON from the ventral striatum. Fluorescent labelling confirmed putative synaptic contacts between VON neurons and olfactory bulb projection neurons. Rabies-virus-mediated trans-synaptic labelling revealed that VON neurons received synaptic inputs from the olfactory bulb, other olfactory cortices, horizontal limb of the diagonal band, and prefrontal cortex. Collectively, these results identify novel GABAergic projection neurons in the olfactory cortex that may integrate olfactory sensory and top-down inputs and send inhibitory output to the LH, which may modulate odour-guided LH-related behaviours.", "classifications": [ { "id": "Miyamichi", "label": "Group Miyamichi", "parent": "Enomoto", "type": "group" }, { "id": "Enomoto", "label": "Team Enomoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Koshi", "last_name": "Murata", "name": null }, { "creator_type": "author", "first_name": "Tomoki", "last_name": "Kinoshita", "name": null }, { "creator_type": "author", "first_name": "Yugo", "last_name": "Fukazawa", "name": null }, { "creator_type": "author", "first_name": "Kenta", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Kazuto", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Kazunari", "last_name": "Miyamichi", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Okuno", "name": null }, { "creator_type": "author", "first_name": "Haruhiko", "last_name": "Bito", "name": null }, { "creator_type": "author", "first_name": "Yoshio", "last_name": "Sakurai", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Yamaguchi", "name": null }, { "creator_type": "author", "first_name": "Kensaku", "last_name": "Mori", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Manabe", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41598-019-43580-1" }, "pmcid": { "normalized": "PMC6509143" }, "pmid": { "normalized": "31073137" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Feeding Behavior", "descriptor_ui": "D005247", "major_topic": false }, { "descriptor": "GABAergic Neurons", "descriptor_ui": "D059330", "major_topic": false }, { "descriptor": "Glutamate Decarboxylase", "descriptor_ui": "D005968", "major_topic": false }, { "descriptor": "Hypothalamic Area, Lateral", "descriptor_ui": "D007026", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Olfactory Bulb", "descriptor_ui": "D009830", "major_topic": false }, { "descriptor": "Olfactory Cortex", "descriptor_ui": "D066194", "major_topic": false }, { "descriptor": "Rabies virus", "descriptor_ui": "D011820", "major_topic": false }, { "descriptor": "Vesicular Glutamate Transport Protein 1", "descriptor_ui": "D050598", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019 May 9", "date_precision": "day", "issue": "1", "normalized_date": "2019-05-09", "pages": "7132", "proceedings_title": null, "publisher": "", "title": "Scientific reports", "volume": "9", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "GABAergic neurons in the olfactory cortex projecting to the lateral hypothalamus in mice.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "To understand the role of RAS-signaling networks in the pathogenesis of renal cell carcisnoma, we clarified the relationship between miR-143 and RAS. The expression of miR-143 was extremely downregulated in tumor tissues from renal cell carcinoma patients compared with that in the adjacent normal tissues and Caki-1 cells. We developed a synthetic miR-143#12, and we found that the ectopic expression of it inhibited cell growth with autophagy in Caki-1 cells. Also, the expression level of c-Myc was markedly decreased, resulting in the perturbation of cancer-specific energy metabolism by negatively modulating the expression of GLUT1 and the PTBP1/PKMs axis. A partial metabolic shift from glycolysis to oxidative phosphorylation induced autophagy through increasing the intracellular level of reactive oxygen species (ROS). In an in vivo study, the potent anti-tumor activity of polyion complex (PIC)-loaded miR-143#12 (miR-143#12/PIC) was shown by systemic administration of it to Caki-1 cell-xenografted mice. Higher levels of miR-143 were found in both blood and tumor tissues after the systemic administration with miR-143#12/PIC compared to those with lipoplexes in the xenografted mice. These findings indicated that this synthetic miR-143#12 induced a marked growth inhibition by impairing K-RAS-signaling networks in vitro and in vivo.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Tomoaki", "last_name": "Takai", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Tsujino", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Yoshikawa", "name": null }, { "creator_type": "author", "first_name": "Teruo", "last_name": "Inamoto", "name": null }, { "creator_type": "author", "first_name": "Nobuhiko", "last_name": "Sugito", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Kuranaga", "name": null }, { "creator_type": "author", "first_name": "Kazuki", "last_name": "Heishima", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Kotaro", "last_name": "Hayashi", "name": null }, { "creator_type": "author", "first_name": "Kanjiro", "last_name": "Miyata", "name": null }, { "creator_type": "author", "first_name": "Kazunori", "last_name": "Kataoka", "name": null }, { "creator_type": "author", "first_name": "Haruhito", "last_name": "Azuma", "name": null }, { "creator_type": "author", "first_name": "Yukihiro", "last_name": "Akao", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.ymthe.2019.03.004" }, "pmcid": { "normalized": "PMC6520334" }, "pmid": { "normalized": "30930112" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Autophagy", "descriptor_ui": "D001343", "major_topic": false }, { "descriptor": "Carcinoma, Renal Cell", "descriptor_ui": "D002292", "major_topic": false }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Cell Proliferation", "descriptor_ui": "D049109", "major_topic": false }, { "descriptor": "Gene Expression Regulation, Neoplastic", "descriptor_ui": "D015972", "major_topic": false }, { "descriptor": "Gene Regulatory Networks", "descriptor_ui": "D053263", "major_topic": false }, { "descriptor": "Glucose Transporter Type 1", "descriptor_ui": "D051272", "major_topic": false }, { "descriptor": "Glycolysis", "descriptor_ui": "D006019", "major_topic": false }, { "descriptor": "Heterogeneous-Nuclear Ribonucleoproteins", "descriptor_ui": "D034441", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "MicroRNAs", "descriptor_ui": "D035683", "major_topic": false }, { "descriptor": "Oxidative Phosphorylation", "descriptor_ui": "D010085", "major_topic": false }, { "descriptor": "Polypyrimidine Tract-Binding Protein", "descriptor_ui": "D038941", "major_topic": false }, { "descriptor": "Proto-Oncogene Proteins c-myc", "descriptor_ui": "D016271", "major_topic": false }, { "descriptor": "Proto-Oncogene Proteins p21(ras)", "descriptor_ui": "D016283", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Xenograft Model Antitumor Assays", "descriptor_ui": "D023041", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019 May 8", "date_precision": "day", "issue": "5", "normalized_date": "2019-05-08", "pages": "1017-1027", "proceedings_title": null, "publisher": "", "title": "Molecular therapy : the journal of the American Society of Gene Therapy", "volume": "27", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "Synthetic miR-143 Exhibited an Anti-Cancer Effect via the Downregulation of K-RAS Networks of Renal Cell Cancer Cells In Vitro and In Vivo.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "A dendritic spine is a small structure on the dendrites of a neuron that processes input timing information from other neurons. Tens of thousands of spines are present on a neuron. Why are spines so small and many? We addressed this issue by using the stochastic simulation model of N-methyl-D-aspartate receptor (NMDAR)-mediated Ca(2+) increase. NMDAR-mediated Ca(2+) increase codes the input timing information between prespiking and postspiking. We examined how much the input timing information is encoded by Ca(2+) increase against presynaptic fluctuation. We found that the input timing information encoded in the cell volume (10(3)mum(3)) largely decreases against the presynaptic fluctuation, whereas that in the spine volume (10(-1)mum(3)) slightly decreases. Therefore, the input timing information encoded in the spine volume is more robust against presynaptic fluctuation than that in the cell volume. We further examined the mechanism of the robust information transfer in the spine volume. We demonstrated that the condition for the robustness is that the stochastic NMDAR-mediated Ca(2+) increase (intrinsic noise) becomes much larger than the presynaptic fluctuation (extrinsic noise). When the presynaptic fluctuation is large, the condition is satisfied in the spine volume but not in the cell volume. Moreover, we compared the input timing information encoded in many small spines with that encoded in a single large spine. We found that the input timing information encoded in many small spines are larger than that in a single large spine when presynaptic fluctuation is large because of their robustness. Thus, robustness is a functional reason why dendritic spines are so small and many.", "classifications": [ { "id": "Kuroda", "label": "Group Kuroda", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Takehiro", "last_name": "Tottori", "name": null }, { "creator_type": "author", "first_name": "Masashi", "last_name": "Fujii", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Kuroda", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.bpj.2019.03.030" }, "pmcid": { "normalized": "PMC6506640" }, "pmid": { "normalized": "31023534" } }, "mesh": [ { "descriptor": "Calcium", "descriptor_ui": "D002118", "major_topic": false }, { "descriptor": "Cell Size", "descriptor_ui": "D048429", "major_topic": false }, { "descriptor": "Dendritic Spines", "descriptor_ui": "D049229", "major_topic": false }, { "descriptor": "Kinetics", "descriptor_ui": "D007700", "major_topic": false }, { "descriptor": "Models, Neurological", "descriptor_ui": "D008959", "major_topic": true }, { "descriptor": "Receptors, N-Methyl-D-Aspartate", "descriptor_ui": "D016194", "major_topic": false }, { "descriptor": "Stochastic Processes", "descriptor_ui": "D013269", "major_topic": false }, { "descriptor": "Synapses", "descriptor_ui": "D013569", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019 May 7", "date_precision": "day", "issue": "9", "normalized_date": "2019-05-07", "pages": "1748-1758", "proceedings_title": null, "publisher": "", "title": "Biophysical journal", "volume": "116", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "NMDAR-Mediated Ca(2+) Increase Shows Robust Information Transfer in Dendritic Spines.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Ca(2+)/calmodulin (CaM)-dependent protein kinase (CaMK) I is activated by the phosphorylation of a crucial activation loop Thr(177) by upstream kinases, CaMK kinase (CaMKK), and regulates axonal or dendritic extension and branching. Reactive sulfur species (RSS) modulate protein functions via polysulfidation of the reactive Cys residues. Here, we report that the activity of CaMKI was reversibly inhibited via its polysulfidation at Cys(179) by RSS. In vitro incubation of CaMKI with the exogenous RSS donor Na(2)S(3) resulted in a dose-dependent inhibition of the phosphorylation at Thr(177) by CaMKK and inactivation of the enzymatic activity. Dithiothreitol (DTT), a small molecule reducing reagent, rescued these inhibitions. Conversely, mutated CaMKI (C179V) was resistant to the Na(2)S(3)-induced inactivation. In transfected cells expressing CaMKI, ionomycin-induced CaMKI activity was decreased upon treatment with Na(2)S(4), whereas cells expressing mutant CaMKI (C179V) proved resistant to this treatment. A biotin-polyethylene glycol-conjugated maleimide capture assay revealed that CaMKI was a target for polysulfidation in cells. Furthermore, the polysulfidation of CaMKI protected Cys(179) from its irreversible modification, known as protein succination. Thus, we propose that CaMKI was reversibly inhibited via polysulfidation of Cys(179) by RSS, thereby protecting it from irreversible modification.", "classifications": [ { "id": "Akaike", "label": "Group Akaike", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Tsuyoshi", "last_name": "Takata", "name": null }, { "creator_type": "author", "first_name": "Ayaka", "last_name": "Tsukuda", "name": null }, { "creator_type": "author", "first_name": "Yukihiro", "last_name": "Tsuchiya", "name": null }, { "creator_type": "author", "first_name": "Takaaki", "last_name": "Akaike", "name": null }, { "creator_type": "author", "first_name": "Yasuo", "last_name": "Watanabe", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.niox.2019.02.008" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "30844494" } }, "mesh": [ { "descriptor": "Amino Acid Substitution", "descriptor_ui": "D019943", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Calcium-Calmodulin-Dependent Protein Kinase Type 1", "descriptor_ui": "D054729", "major_topic": false }, { "descriptor": "Catalytic Domain", "descriptor_ui": "D020134", "major_topic": false }, { "descriptor": "Cystathionine gamma-Lyase", "descriptor_ui": "D003542", "major_topic": false }, { "descriptor": "Cysteine", "descriptor_ui": "D003545", "major_topic": false }, { "descriptor": "Dithiothreitol", "descriptor_ui": "D004229", "major_topic": false }, { "descriptor": "Enzyme Inhibitors", "descriptor_ui": "D004791", "major_topic": false }, { "descriptor": "Enzyme Reactivators", "descriptor_ui": "D004793", "major_topic": false }, { "descriptor": "HEK293 Cells", "descriptor_ui": "D057809", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Phosphorylation", "descriptor_ui": "D010766", "major_topic": false }, { "descriptor": "Protein Processing, Post-Translational", "descriptor_ui": "D011499", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Sulfides", "descriptor_ui": "D013440", "major_topic": false }, { "descriptor": "Threonine", "descriptor_ui": "D013912", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019 May 1", "date_precision": "day", "issue": "", "normalized_date": "2019-05-01", "pages": "68-75", "proceedings_title": null, "publisher": "", "title": "Nitric oxide : biology and chemistry", "volume": "86", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "The active-site cysteine residue of Ca(2+)/calmodulin-dependent protein kinase I is protected from irreversible modification via generation of polysulfidation.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Somatic stem/progenitor cells are active in embryonic tissues but quiescent in many adult tissues. The detailed mechanisms that regulate active versus quiescent stem cell states are largely unknown. In active neural stem cells, Hes1 expression oscillates and drives cyclic expression of the proneural gene Ascl1, which activates cell proliferation. Here, we found that in quiescent neural stem cells in the adult mouse brain, Hes1 levels are oscillatory, although the peaks and troughs are higher than those in active neural stem cells, causing Ascl1 expression to be continuously suppressed. Inactivation of Hes1 and its related genes up-regulates Ascl1 expression and increases neurogenesis. This causes rapid depletion of neural stem cells and premature termination of neurogenesis. Conversely, sustained Hes1 expression represses Ascl1, inhibits neurogenesis, and maintains quiescent neural stem cells. In contrast, induction of Ascl1 oscillations activates neural stem cells and increases neurogenesis in the adult mouse brain. Thus, Ascl1 oscillations, which normally depend on Hes1 oscillations, regulate the active state, while high Hes1 expression and resultant Ascl1 suppression promote quiescence in neural stem cells.", "classifications": [ { "id": "Imayoshi", "label": "Group Imayoshi", "parent": "Imayoshi", "type": "group" }, { "id": "Imayoshi", "label": "Team Imayoshi", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Risa", "last_name": "Sueda", "name": null }, { "creator_type": "author", "first_name": "Itaru", "last_name": "Imayoshi", "name": null }, { "creator_type": "author", "first_name": "Yukiko", "last_name": "Harima", "name": null }, { "creator_type": "author", "first_name": "Ryoichiro", "last_name": "Kageyama", "name": null } ], "identifiers": { "doi": { "normalized": "10.1101/gad.323196.118" }, "pmcid": { "normalized": "PMC6499325" }, "pmid": { "normalized": "30862661" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Basic Helix-Loop-Helix Proteins", "descriptor_ui": "D051792", "major_topic": false }, { "descriptor": "Brain", "descriptor_ui": "D001921", "major_topic": false }, { "descriptor": "Gene Expression Profiling", "descriptor_ui": "D020869", "major_topic": false }, { "descriptor": "Gene Expression Regulation", "descriptor_ui": "D005786", "major_topic": true }, { "descriptor": "Gene Silencing", "descriptor_ui": "D020868", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Neural Stem Cells", "descriptor_ui": "D058953", "major_topic": true }, { "descriptor": "Neurogenesis", "descriptor_ui": "D055495", "major_topic": false }, { "descriptor": "Optogenetics", "descriptor_ui": "D062308", "major_topic": false }, { "descriptor": "Promoter Regions, Genetic", "descriptor_ui": "D011401", "major_topic": false }, { "descriptor": "Transcription Factor HES-1", "descriptor_ui": "D000072056", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019 May 1", "date_precision": "day", "issue": "9-10", "normalized_date": "2019-05-01", "pages": "511-523", "proceedings_title": null, "publisher": "", "title": "Genes & development", "volume": "33", "year": 2019 }, "ssbd": { "database": [ "ssbd-database-000196" ], "repository": [ "ssbd-repos-000196" ] }, "title": "High Hes1 expression and resultant Ascl1 suppression regulate quiescent vs. active neural stem cells in the adult mouse brain.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Intracellular polysulfide could regulate the redox balance via its anti-oxidant activity. However, the existence of polysulfide in biological fluids still remains unknown. Recently, we developed a quantitative analytical method for polysulfide and discovered that polysulfide exists in plasma and responds to oxidative stress. In this study, we confirmed the presence of polysulfide in other biological fluids, such as semen and nasal discharge. The levels of polysulfide in these biological fluids from healthy volunteers (n = 9) with identical characteristics were compared. Additionally, the circadian rhythm of plasma polysulfide was also investigated. The polysulfide levels detected from nasal discharge and seminal fluid were approximately 400 and 600 muM, respectively. No correlation could be found between plasma polysulfide and the polysulfide levels of tear, saliva, and nasal discharge. On the other hand, seminal polysulfide was positively correlated with plasma polysulfide, and almost all polysulfide contained in semen was found in seminal fluid. Intriguingly, saliva and seminal polysulfide strongly correlated with salivary amylase and sperm activities, respectively. These results provide a foundation for scientific breakthroughs in various research areas like infertility and the digestive system process.", "classifications": [ { "id": "Akaike", "label": "Group Akaike", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Mayumi", "last_name": "Ikeda", "name": null }, { "creator_type": "author", "first_name": "Yu", "last_name": "Ishima", "name": null }, { "creator_type": "author", "first_name": "Victor T. G.", "last_name": "Chuang", "name": null }, { "creator_type": "author", "first_name": "Maki", "last_name": "Sakai", "name": null }, { "creator_type": "author", "first_name": "Hiroki", "last_name": "Osafune", "name": null }, { "creator_type": "author", "first_name": "Hidenori", "last_name": "Ando", "name": null }, { "creator_type": "author", "first_name": "Taro", "last_name": "Shimizu", "name": null }, { "creator_type": "author", "first_name": "Keiichiro", "last_name": "Okuhira", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Toru", "last_name": "Maruyama", "name": null }, { "creator_type": "author", "first_name": "Masaki", "last_name": "Otagiri", "name": null }, { "creator_type": "author", "first_name": "Takaaki", "last_name": "Akaike", "name": null }, { "creator_type": "author", "first_name": "Tatsuhiro", "last_name": "Ishida", "name": null } ], "identifiers": { "doi": { "normalized": "10.3390/molecules24091689" }, "pmcid": { "normalized": "PMC6539915" }, "pmid": { "normalized": "31052207" } }, "mesh": [ { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Age Factors", "descriptor_ui": "D000367", "major_topic": false }, { "descriptor": "Amylases", "descriptor_ui": "D000681", "major_topic": false }, { "descriptor": "Biomarkers", "descriptor_ui": "D015415", "major_topic": false }, { "descriptor": "Body Fluids", "descriptor_ui": "D001826", "major_topic": false }, { "descriptor": "Body Mass Index", "descriptor_ui": "D015992", "major_topic": false }, { "descriptor": "Circadian Rhythm", "descriptor_ui": "D002940", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Proteins", "descriptor_ui": "D011506", "major_topic": false }, { "descriptor": "Sex Factors", "descriptor_ui": "D012737", "major_topic": false }, { "descriptor": "Sperm Count", "descriptor_ui": "D013076", "major_topic": false }, { "descriptor": "Sperm Motility", "descriptor_ui": "D013081", "major_topic": false }, { "descriptor": "Spermatozoa", "descriptor_ui": "D013094", "major_topic": false }, { "descriptor": "Sulfides", "descriptor_ui": "D013440", "major_topic": false }, { "descriptor": "Young Adult", "descriptor_ui": "D055815", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019 Apr 30", "date_precision": "day", "issue": "9", "normalized_date": "2019-04-30", "pages": "", "proceedings_title": null, "publisher": "", "title": "Molecules (Basel, Switzerland)", "volume": "24", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "Distribution of Polysulfide in Human Biological Fluids and Their Association with Amylase and Sperm Activities.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "We present evidence for the decomposition and oxidation of amino acids in aqueous solution following irradiation with a nonequilibrium plasma jet. Of 15 amino acids tested in cell culture medium, plasma irradiation induced a marked chemical change in methionine and tryptophan due to the effective production of reactive oxygen species by plasma-water interaction. We also report that plasma-treated methionine and tryptophan aqueous solutions can kill cancer cells, greatly decreasing the viability of human endometrial carcinoma (HEC-1) cancer cells due to the presence of decomposition or oxidation products generated from the amino acid. Plasma-treated methionine and tryptophan aqueous solutions also induced an anti-cancer effect on cancer-initiating cells.", "classifications": [ { "id": "Suzuki", "label": "Group Suzuki", "parent": "Takekawa", "type": "group" }, { "id": "Takekawa", "label": "Team Takekawa", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Giichiro", "last_name": "Uchida", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Mino", "name": null }, { "creator_type": "author", "first_name": "Tensho", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Jun-Ichiro", "last_name": "Ikeda", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Kosuke", "last_name": "Takenaka", "name": null }, { "creator_type": "author", "first_name": "Yuichi", "last_name": "Setsuhara", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41598-019-42959-4" }, "pmcid": { "normalized": "PMC6488654" }, "pmid": { "normalized": "31036847" } }, "mesh": [ { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Cell Survival", "descriptor_ui": "D002470", "major_topic": false }, { "descriptor": "Endometrial Neoplasms", "descriptor_ui": "D016889", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Methionine", "descriptor_ui": "D008715", "major_topic": false }, { "descriptor": "Plasma Gases", "descriptor_ui": "D058626", "major_topic": false }, { "descriptor": "Reactive Oxygen Species", "descriptor_ui": "D017382", "major_topic": false }, { "descriptor": "Tryptophan", "descriptor_ui": "D014364", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019 Apr 29", "date_precision": "day", "issue": "1", "normalized_date": "2019-04-29", "pages": "6625", "proceedings_title": null, "publisher": "", "title": "Scientific reports", "volume": "9", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "Decomposition and oxidation of methionine and tryptophan following irradiation with a nonequilibrium plasma jet and applications for killing cancer cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Diabetic kidney disease is a major cause of renal failure that urgently necessitates a breakthrough in disease management. Here we show using untargeted metabolomics that levels of phenyl sulfate, a gut microbiota-derived metabolite, increase with the progression of diabetes in rats overexpressing human uremic toxin transporter SLCO4C1 in the kidney, and are decreased in rats with limited proteinuria. In experimental models of diabetes, phenyl sulfate administration induces albuminuria and podocyte damage. In a diabetic patient cohort, phenyl sulfate levels significantly correlate with basal and predicted 2-year progression of albuminuria in patients with microalbuminuria. Inhibition of tyrosine phenol-lyase, a bacterial enzyme responsible for the synthesis of phenol from dietary tyrosine before it is metabolized into phenyl sulfate in the liver, reduces albuminuria in diabetic mice. Together, our results suggest that phenyl sulfate contributes to albuminuria and could be used as a disease marker and future therapeutic target in diabetic kidney disease.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Suzuki", "label": "Group Suzuki", "parent": "Takekawa", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" }, { "id": "Takekawa", "label": "Team Takekawa", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Koichi", "last_name": "Kikuchi", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Saigusa", "name": null }, { "creator_type": "author", "first_name": "Yoshitomi", "last_name": "Kanemitsu", "name": null }, { "creator_type": "author", "first_name": "Yotaro", "last_name": "Matsumoto", "name": null }, { "creator_type": "author", "first_name": "Paxton", "last_name": "Thanai", "name": null }, { "creator_type": "author", "first_name": "Naoto", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Koki", "last_name": "Mise", "name": null }, { "creator_type": "author", "first_name": "Hiroaki", "last_name": "Yamaguchi", "name": null }, { "creator_type": "author", "first_name": "Tomohiro", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Kei", "last_name": "Asaji", "name": null }, { "creator_type": "author", "first_name": "Chikahisa", "last_name": "Mukawa", "name": null }, { "creator_type": "author", "first_name": "Hiroki", "last_name": "Tsukamoto", "name": null }, { "creator_type": "author", "first_name": "Toshihiro", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Yoshitsugu", "last_name": "Oikawa", "name": null }, { "creator_type": "author", "first_name": "Tomoyuki", "last_name": "Iwasaki", "name": null }, { "creator_type": "author", "first_name": "Yuji", "last_name": "Oe", "name": null }, { "creator_type": "author", "first_name": "Tomoya", "last_name": "Tsukimi", "name": null }, { "creator_type": "author", "first_name": "Noriko N.", "last_name": "Fukuda", "name": null }, { "creator_type": "author", "first_name": "Hsin-Jung", "last_name": "Ho", "name": null }, { "creator_type": "author", "first_name": "Fumika", "last_name": "Nanto-Hara", "name": null }, { "creator_type": "author", "first_name": "Jiro", "last_name": "Ogura", "name": null }, { "creator_type": "author", "first_name": "Ritsumi", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Shizuko", "last_name": "Nagao", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Ohsaki", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Shimada", "name": null }, { "creator_type": "author", "first_name": "Takehiro", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Takafumi", "last_name": "Toyohara", "name": null }, { "creator_type": "author", "first_name": "Eikan", "last_name": "Mishima", "name": null }, { "creator_type": "author", "first_name": "Hisato", "last_name": "Shima", "name": null }, { "creator_type": "author", "first_name": "Yasutoshi", "last_name": "Akiyama", "name": null }, { "creator_type": "author", "first_name": "Yukako", "last_name": "Akiyama", "name": null }, { "creator_type": "author", "first_name": "Mariko", "last_name": "Ichijo", "name": null }, { "creator_type": "author", "first_name": "Tetsuro", "last_name": "Matsuhashi", "name": null }, { "creator_type": "author", "first_name": "Akihiro", "last_name": "Matsuo", "name": null }, { "creator_type": "author", "first_name": "Yoshiaki", "last_name": "Ogata", "name": null }, { "creator_type": "author", "first_name": "Ching-Chin", "last_name": "Yang", "name": null }, { "creator_type": "author", "first_name": "Chitose", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Matthew C.", "last_name": "Breeggemann", "name": null }, { "creator_type": "author", "first_name": "Jurgen", "last_name": "Heymann", "name": null }, { "creator_type": "author", "first_name": "Miho", "last_name": "Shimizu", "name": null }, { "creator_type": "author", "first_name": "Susumu", "last_name": "Ogawa", "name": null }, { "creator_type": "author", "first_name": "Nobuyuki", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Yuji", "last_name": "Owada", "name": null }, { "creator_type": "author", "first_name": "Shigeo", "last_name": "Kure", "name": null }, { "creator_type": "author", "first_name": "Nariyasu", "last_name": "Mano", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Wada", "name": null }, { "creator_type": "author", "first_name": "Jeffrey B.", "last_name": "Kopp", "name": null }, { "creator_type": "author", "first_name": "Shinji", "last_name": "Fukuda", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Hozawa", "name": null }, { "creator_type": "author", "first_name": "Masayuki", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Sadayoshi", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Jun", "last_name": "Wada", "name": null }, { "creator_type": "author", "first_name": "Yoshihisa", "last_name": "Tomioka", "name": null }, { "creator_type": "author", "first_name": "Takaaki", "last_name": "Abe", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41467-019-09735-4" }, "pmcid": { "normalized": "PMC6478834" }, "pmid": { "normalized": "31015435" } }, "mesh": [ { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Aged, 80 and over", "descriptor_ui": "D000369", "major_topic": false }, { "descriptor": "Albuminuria", "descriptor_ui": "D000419", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Animals, Genetically Modified", "descriptor_ui": "D030801", "major_topic": false }, { "descriptor": "Cohort Studies", "descriptor_ui": "D015331", "major_topic": false }, { "descriptor": "Diabetes Mellitus, Experimental", "descriptor_ui": "D003921", "major_topic": false }, { "descriptor": "Diabetes Mellitus, Type 1", "descriptor_ui": "D003922", "major_topic": false }, { "descriptor": "Diabetes Mellitus, Type 2", "descriptor_ui": "D003924", "major_topic": false }, { "descriptor": "Diabetic Nephropathies", "descriptor_ui": "D003928", "major_topic": false }, { "descriptor": "Dogs", "descriptor_ui": "D004285", "major_topic": false }, { "descriptor": "Enzyme Inhibitors", "descriptor_ui": "D004791", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Gastrointestinal Microbiome", "descriptor_ui": "D000069196", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Madin Darby Canine Kidney Cells", "descriptor_ui": "D061985", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Metabolomics", "descriptor_ui": "D055432", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Organic Anion Transporters", "descriptor_ui": "D027361", "major_topic": false }, { "descriptor": "Podocytes", "descriptor_ui": "D050199", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Streptozocin", "descriptor_ui": "D013311", "major_topic": false }, { "descriptor": "Sulfuric Acid Esters", "descriptor_ui": "D013463", "major_topic": false }, { "descriptor": "Tyrosine Phenol-Lyase", "descriptor_ui": "D014447", "major_topic": false }, { "descriptor": "Young Adult", "descriptor_ui": "D055815", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019 Apr 23", "date_precision": "day", "issue": "1", "normalized_date": "2019-04-23", "pages": "1835", "proceedings_title": null, "publisher": "", "title": "Nature communications", "volume": "10", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "Gut microbiome-derived phenyl sulfate contributes to albuminuria in diabetic kidney disease.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The genome is packaged and organized in an ordered, nonrandom manner, and specific chromatin segments contact nuclear substructures to mediate this organization. tRNA genes (tDNAs) are binding sites for transcription factors and architectural proteins and are thought to play an important role in the organization of the genome. In this study, we investigate the roles of tDNAs in genomic organization and chromosome function by editing a chromosome so that it lacked any tDNAs. Surprisingly our analyses of this tDNA-less chromosome show that loss of tDNAs does not grossly affect chromatin architecture or chromosome tethering and mobility. However, loss of tDNAs affects local nucleosome positioning and the binding of SMC proteins at these loci. The absence of tDNAs also leads to changes in centromere clustering and a reduction in the frequency of long-range HML-HMR heterochromatin clustering with concomitant effects on gene silencing. We propose that the tDNAs primarily affect local chromatin structure, which results in effects on long-range chromosome architecture.", "classifications": [ { "id": "Kobayashi", "label": "Group Kobayashi", "parent": "Wakamoto", "type": "group" }, { "id": "Wakamoto", "label": "Team Wakamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Omar", "last_name": "Hamdani", "name": null }, { "creator_type": "author", "first_name": "Namrita", "last_name": "Dhillon", "name": null }, { "creator_type": "author", "first_name": "Tsung-Han S.", "last_name": "Hsieh", "name": null }, { "creator_type": "author", "first_name": "Takahiro", "last_name": "Fujita", "name": null }, { "creator_type": "author", "first_name": "Josefina", "last_name": "Ocampo", "name": null }, { "creator_type": "author", "first_name": "Jacob G.", "last_name": "Kirkland", "name": null }, { "creator_type": "author", "first_name": "Josh", "last_name": "Lawrimore", "name": null }, { "creator_type": "author", "first_name": "Tetsuya J.", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Brandon", "last_name": "Friedman", "name": null }, { "creator_type": "author", "first_name": "Derek", "last_name": "Fulton", "name": null }, { "creator_type": "author", "first_name": "Kenneth Y.", "last_name": "Wu", "name": null }, { "creator_type": "author", "first_name": "Razvan V.", "last_name": "Chereji", "name": null }, { "creator_type": "author", "first_name": "Masaya", "last_name": "Oki", "name": null }, { "creator_type": "author", "first_name": "Kerry", "last_name": "Bloom", "name": null }, { "creator_type": "author", "first_name": "David J.", "last_name": "Clark", "name": null }, { "creator_type": "author", "first_name": "Oliver J.", "last_name": "Rando", "name": null }, { "creator_type": "author", "first_name": "Rohinton T.", "last_name": "Kamakaka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1128/mcb.00432-18" }, "pmcid": { "normalized": "PMC6447413" }, "pmid": { "normalized": "30718362" } }, "mesh": [ { "descriptor": "Binding Sites", "descriptor_ui": "D001665", "major_topic": false }, { "descriptor": "Cell Nucleus", "descriptor_ui": "D002467", "major_topic": false }, { "descriptor": "Chromatin", "descriptor_ui": "D002843", "major_topic": false }, { "descriptor": "Chromatin Assembly and Disassembly", "descriptor_ui": "D042002", "major_topic": false }, { "descriptor": "Chromosomes", "descriptor_ui": "D002875", "major_topic": false }, { "descriptor": "Heterochromatin", "descriptor_ui": "D006570", "major_topic": false }, { "descriptor": "RNA, Transfer", "descriptor_ui": "D012343", "major_topic": false }, { "descriptor": "Saccharomyces cerevisiae", "descriptor_ui": "D012441", "major_topic": false }, { "descriptor": "Saccharomyces cerevisiae Proteins", "descriptor_ui": "D029701", "major_topic": false }, { "descriptor": "Transcription Factors, TFIII", "descriptor_ui": "D019474", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019 Apr 15", "date_precision": "day", "issue": "8", "normalized_date": "2019-04-15", "pages": "e00432-18", "proceedings_title": null, "publisher": "", "title": "Molecular and cellular biology", "volume": "39", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "tRNA Genes Affect Chromosome Structure and Function via Local Effects.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Kinetic simulation is a useful approach for elucidating complex cell-signaling systems. The numerical simulations required for kinetic modeling in live cells critically require parameters such as protein concentrations and dissociation constants (Kd ). However, only a limited number of parameters have been measured experimentally in living cells. Here we describe an approach for quantifying the concentration and Kd of endogenous proteins at the single-cell level with CRISPR/Cas9-mediated knock-in and fluorescence cross-correlation spectroscopy. First, the mEGFP gene was knocked in at the end of the mitogen-activated protein kinase 1 (MAPK1) gene, encoding extracellular signal-regulated kinase 2 (ERK2), through homology-directed repair or microhomology-mediated end joining. Next, the HaloTag gene was knocked in at the end of the ribosomal S6 kinase 2 (RSK2) gene. We then used fluorescence correlation spectroscopy to measure the protein concentrations of endogenous ERK2-mEGFP and RSK2-HaloTag fusion constructs in living cells, revealing substantial heterogeneities. Moreover, fluorescence cross-correlation spectroscopy analyses revealed temporal changes in the apparent Kd values of the binding between ERK2-mEGFP and RSK2-HaloTag in response to epidermal growth factor stimulation. Our approach presented here provides a robust and efficient method for quantifying endogenous protein concentrations and dissociation constants in living cells.", "classifications": [], "creators": [ { "creator_type": "author", "first_name": "Akira T.", "last_name": "Komatsubara", "name": null }, { "creator_type": "author", "first_name": "Yuhei", "last_name": "Goto", "name": null }, { "creator_type": "author", "first_name": "Yohei", "last_name": "Kondo", "name": null }, { "creator_type": "author", "first_name": "Michiyuki", "last_name": "Matsuda", "name": null }, { "creator_type": "author", "first_name": "Kazuhiro", "last_name": "Aoki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1074/jbc.ra119.007685" }, "pmcid": { "normalized": "PMC6463716" }, "pmid": { "normalized": "30739083" } }, "mesh": [ { "descriptor": "CRISPR-Cas Systems", "descriptor_ui": "D064113", "major_topic": false }, { "descriptor": "Green Fluorescent Proteins", "descriptor_ui": "D049452", "major_topic": false }, { "descriptor": "HEK293 Cells", "descriptor_ui": "D057809", "major_topic": false }, { "descriptor": "HeLa Cells", "descriptor_ui": "D006367", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mitogen-Activated Protein Kinase 1", "descriptor_ui": "D019950", "major_topic": false }, { "descriptor": "Ribosomal Protein S6 Kinases, 90-kDa", "descriptor_ui": "D038744", "major_topic": false }, { "descriptor": "Spectrometry, Fluorescence", "descriptor_ui": "D013050", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019 Apr 12", "date_precision": "day", "issue": "15", "normalized_date": "2019-04-12", "pages": "6062-6072", "proceedings_title": null, "publisher": "", "title": "The Journal of biological chemistry", "volume": "294", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "Single-cell quantification of the concentrations and dissociation constants of endogenous proteins.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Gefitinib, one of the tyrosine kinase inhibitors of epidermal growth factor receptor (EGFR), is effective for treating lung adenocarcinoma harboring EGFR mutation; but later, most cases acquire a resistance to gefitinib. One of the mechanisms conferring gefitinib resistance to lung adenocarcinoma is the amplification of the MET gene, which is observed in 5-22% of gefitinib-resistant tumors. A previous study suggested that MET amplification could cause gefitinib resistance by driving ErbB3-dependent activation of the PI3K pathway. In this study, we built a mathematical model of gefitinib resistance caused by MET amplification using lung adenocarcinoma HCC827-GR (gefitinib resistant) cells. The molecular reactions involved in gefitinib resistance consisted of dimerization and phosphorylation of three molecules, EGFR, ErbB3, and MET were described by a series of ordinary differential equations. To perform a computer simulation, we quantified each molecule on the cell surface using flow cytometry and estimated unknown parameters by dimensional analysis. Our simulation showed that the number of active ErbB3 molecules is around a hundred-fold smaller than that of active MET molecules. Limited contribution of ErbB3 in gefitinib resistance by MET amplification is also demonstrated using HCC827-GR cells in culture experiments. Our mathematical model provides a quantitative understanding of the molecular reactions underlying drug resistance.", "classifications": [ { "id": "Suzuki", "label": "Group Suzuki", "parent": "Takekawa", "type": "group" }, { "id": "Takekawa", "label": "Team Takekawa", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Takeshi", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Kumagai", "name": null }, { "creator_type": "author", "first_name": "Keiko", "last_name": "Itano", "name": null }, { "creator_type": "author", "first_name": "Tomoko", "last_name": "Maruyama", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Tamura", "name": null }, { "creator_type": "author", "first_name": "Shuji", "last_name": "Kawasaki", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Yoshinori", "last_name": "Murakami", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.bbrc.2019.02.086" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "30824185" } }, "mesh": [ { "descriptor": "Adenocarcinoma of Lung", "descriptor_ui": "D000077192", "major_topic": false }, { "descriptor": "Antineoplastic Agents", "descriptor_ui": "D000970", "major_topic": false }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Computer Simulation", "descriptor_ui": "D003198", "major_topic": false }, { "descriptor": "Drug Resistance, Neoplasm", "descriptor_ui": "D019008", "major_topic": false }, { "descriptor": "Gefitinib", "descriptor_ui": "D000077156", "major_topic": false }, { "descriptor": "Gene Amplification", "descriptor_ui": "D005784", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Lung Neoplasms", "descriptor_ui": "D008175", "major_topic": false }, { "descriptor": "Models, Biological", "descriptor_ui": "D008954", "major_topic": false }, { "descriptor": "Proto-Oncogene Proteins c-met", "descriptor_ui": "D019859", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019 Apr 9", "date_precision": "day", "issue": "3", "normalized_date": "2019-04-09", "pages": "544-550", "proceedings_title": null, "publisher": "", "title": "Biochemical and biophysical research communications", "volume": "511", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "Mathematical analysis of gefitinib resistance of lung adenocarcinoma caused by MET amplification.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Mitochondrial activity is a widely used criterion to judge the metabolic condition of a living specimen. Numerous methods have been developed for related analyses, including the detection of O2 consumption, trans-membrane potential, and ATP production. In this study, we demonstrate that the redox state of cytochromes can serve as a sensitive mitochondrial activity indicator in glutamate-stressed neuronal cells. Mitochondrial dysfunction was detected by Raman imaging as early as 30 min after glutamate-stress induction. By comparing this result with other commonly used mitochondrial function assays, we found Raman imaging has a similar sensitivity to ATP production and trans-membrane potential assays. Other viability tests, such as MTT assay and ROS production tests, showed a slower response than our method. A thorough understanding of cytochrome dynamics with our new method will help establish Raman spectroscopy as a competitive clinical diagnosis tool for neurodegenerative diseases involving mitochondrial dysfunction.", "classifications": [ { "id": "Fujita", "label": "Group Fujita", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Takeshi", "last_name": "Morimoto", "name": null }, { "creator_type": "author", "first_name": "Liang-da", "last_name": "Chiu", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Kanda", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Kawagoe", "name": null }, { "creator_type": "author", "first_name": "Takeaki", "last_name": "Ozawa", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Kohji", "last_name": "Nishida", "name": null }, { "creator_type": "author", "first_name": "Katsumasa", "last_name": "Fujita", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Fujikado", "name": null } ], "identifiers": { "doi": { "normalized": "10.1039/c8an02213e" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "30839952" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "Cytochromes", "descriptor_ui": "D003580", "major_topic": false }, { "descriptor": "Glutamic Acid", "descriptor_ui": "D018698", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mitochondria", "descriptor_ui": "D008928", "major_topic": false }, { "descriptor": "Mitochondrial Diseases", "descriptor_ui": "D028361", "major_topic": false }, { "descriptor": "Oxidation-Reduction", "descriptor_ui": "D010084", "major_topic": false }, { "descriptor": "Spectrum Analysis, Raman", "descriptor_ui": "D013059", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019 Apr 8", "date_precision": "day", "issue": "8", "normalized_date": "2019-04-08", "pages": "2531-2540", "proceedings_title": null, "publisher": "", "title": "The Analyst", "volume": "144", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "Using redox-sensitive mitochondrial cytochrome Raman bands for label-free detection of mitochondrial dysfunction.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Selective autophagy ensures the removal of specific soluble proteins, protein aggregates, damaged mitochondria, and invasive bacteria from cells. Defective autophagy has been directly linked to metabolic disorders. However how selective autophagy regulates metabolism remains largely uncharacterized. Here we show that a deficiency in selective autophagy is associated with suppression of lipid oxidation. Hepatic loss of Atg7 or Atg5 significantly impairs the production of ketone bodies upon fasting, due to decreased expression of enzymes involved in beta-oxidation following suppression of transactivation by PPARalpha. Mechanistically, nuclear receptor co-repressor 1 (NCoR1), which interacts with PPARalpha to suppress its transactivation, binds to the autophagosomal GABARAP family proteins and is degraded by autophagy. Consequently, loss of autophagy causes accumulation of NCoR1, suppressing PPARalpha activity and resulting in impaired lipid oxidation. These results suggest that autophagy contributes to PPARalpha activation upon fasting by promoting degradation of NCoR1 and thus regulates beta-oxidation and ketone bodies production.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Tetsuya", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Akiko", "last_name": "Kuma", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Sugiura", "name": null }, { "creator_type": "author", "first_name": "Yoshinobu", "last_name": "Ichimura", "name": null }, { "creator_type": "author", "first_name": "Miki", "last_name": "Obata", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Kitamura", "name": null }, { "creator_type": "author", "first_name": "Shujiro", "last_name": "Okuda", "name": null }, { "creator_type": "author", "first_name": "Hyeon-Cheol", "last_name": "Lee", "name": null }, { "creator_type": "author", "first_name": "Kazutaka", "last_name": "Ikeda", "name": null }, { "creator_type": "author", "first_name": "Yumi", "last_name": "Kanegae", "name": null }, { "creator_type": "author", "first_name": "Izumu", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Johan", "last_name": "Auwerx", "name": null }, { "creator_type": "author", "first_name": "Hozumi", "last_name": "Motohashi", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Suematsu", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Takehiko", "last_name": "Yokomizo", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Waguri", "name": null }, { "creator_type": "author", "first_name": "Noboru", "last_name": "Mizushima", "name": null }, { "creator_type": "author", "first_name": "Masaaki", "last_name": "Komatsu", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41467-019-08829-3" }, "pmcid": { "normalized": "PMC6450892" }, "pmid": { "normalized": "30952864" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Autophagy", "descriptor_ui": "D001343", "major_topic": true }, { "descriptor": "Autophagy-Related Protein 5", "descriptor_ui": "D000071187", "major_topic": false }, { "descriptor": "Autophagy-Related Protein 7", "descriptor_ui": "D000071193", "major_topic": false }, { "descriptor": "Fasting", "descriptor_ui": "D005215", "major_topic": false }, { "descriptor": "Ketone Bodies", "descriptor_ui": "D007657", "major_topic": false }, { "descriptor": "Lipid Metabolism", "descriptor_ui": "D050356", "major_topic": true }, { "descriptor": "Liver", "descriptor_ui": "D008099", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Nuclear Receptor Co-Repressor 1", "descriptor_ui": "D056971", "major_topic": false }, { "descriptor": "Oxidation-Reduction", "descriptor_ui": "D010084", "major_topic": false }, { "descriptor": "PPAR alpha", "descriptor_ui": "D047493", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019 Apr 5", "date_precision": "day", "issue": "1", "normalized_date": "2019-04-05", "pages": "1567", "proceedings_title": null, "publisher": "", "title": "Nature communications", "volume": "10", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "Autophagy regulates lipid metabolism through selective turnover of NCoR1.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "We designed a conjugated molecule bearing an O-nitrobenzoxadiazole (O-NBD) unit and an acetylated trimethyl lock as a chromogenic and fluorogenic probe for the detection of esterase activity. The designed molecule was briefly synthesized from a commercially available compound in two steps. Several experiments revealed that the conjugated molecule serves as a sensitive chromogenic and fluorogenic probe for the detection of porcine liver esterase activity. Mechanistic studies indicated that an intramolecular O- to N-NBD migration is involved in the chromogenic/fluorogenic phenomena. The results here would be helpful for designing other O-NBD-based chromogenic/fluorogenic probes in future.", "classifications": [ { "id": "Sodeoka", "label": "Group Sodeoka", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Kana", "last_name": "Okada", "name": null }, { "creator_type": "author", "first_name": "Takao", "last_name": "Yamaguchi", "name": null }, { "creator_type": "author", "first_name": "Kosuke", "last_name": "Dodo", "name": null }, { "creator_type": "author", "first_name": "Mikiko", "last_name": "Sodeoka", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Obika", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.bmc.2019.02.036" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "30795989" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Chromogenic Compounds", "descriptor_ui": "D002863", "major_topic": false }, { "descriptor": "Esterases", "descriptor_ui": "D004950", "major_topic": false }, { "descriptor": "Fluorescent Dyes", "descriptor_ui": "D005456", "major_topic": false }, { "descriptor": "Liver", "descriptor_ui": "D008099", "major_topic": false }, { "descriptor": "Molecular Structure", "descriptor_ui": "D015394", "major_topic": false }, { "descriptor": "Nitrobenzenes", "descriptor_ui": "D009578", "major_topic": false }, { "descriptor": "Oxadiazoles", "descriptor_ui": "D010069", "major_topic": false }, { "descriptor": "Swine", "descriptor_ui": "D013552", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019 Apr 1", "date_precision": "day", "issue": "7", "normalized_date": "2019-04-01", "pages": "1444-1448", "proceedings_title": null, "publisher": "", "title": "Bioorganic & medicinal chemistry", "volume": "27", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "Detection of esterase activity by chromogenic and fluorogenic probe based on an O-nitrobenzoxadiazole (O-NBD) unit.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Functional genomics approaches can overcome limitations—such as the lack of identification of robust targets and poor clinical efficacy—that hamper cancer drug development. Here we performed genome-scale CRISPR–Cas9 screens in 324 human cancer cell lines from 30 cancer types and developed a data-driven framework to prioritize candidates for cancer therapeutics. We integrated cell fitness effects with genomic biomarkers and target tractability for drug development to systematically prioritize new targets in defined tissues and genotypes. We verified one of our most promising dependencies, the Werner syndrome ATP-dependent helicase, as a synthetic lethal target in tumours from multiple cancer types with microsatellite instability. Our analysis provides a resource of cancer dependencies, generates a framework to prioritize cancer drug targets and suggests specific new targets. The principles described in this study can inform the initial stages of drug development by contributing to a new, diverse and more effective portfolio of cancer drug targets.", "classifications": [ { "id": "Yusa", "label": "Group Yusa", "parent": "Eiraku", "type": "group" }, { "id": "Eiraku", "label": "Team Eiraku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Fiona M.", "last_name": "Behan", "name": null }, { "creator_type": "author", "first_name": "Francesco", "last_name": "Iorio", "name": null }, { "creator_type": "author", "first_name": "Gabriele", "last_name": "Picco", "name": null }, { "creator_type": "author", "first_name": "Emanuel", "last_name": "Gonçalves", "name": null }, { "creator_type": "author", "first_name": "Charlotte M.", "last_name": "Beaver", "name": null }, { "creator_type": "author", "first_name": "Giorgia", "last_name": "Migliardi", "name": null }, { "creator_type": "author", "first_name": "Rita", "last_name": "Santos", "name": null }, { "creator_type": "author", "first_name": "Yanhua", "last_name": "Rao", "name": null }, { "creator_type": "author", "first_name": "Francesco", "last_name": "Sassi", "name": null }, { "creator_type": "author", "first_name": "Marika", "last_name": "Pinnelli", "name": null }, { "creator_type": "author", "first_name": "Rizwan", "last_name": "Ansari", "name": null }, { "creator_type": "author", "first_name": "Sarah", "last_name": "Harper", "name": null }, { "creator_type": "author", "first_name": "David Adam", "last_name": "Jackson", "name": null }, { "creator_type": "author", "first_name": "Rebecca", "last_name": "McRae", "name": null }, { "creator_type": "author", "first_name": "Rachel", "last_name": "Pooley", "name": null }, { "creator_type": "author", "first_name": "Piers", "last_name": "Wilkinson", "name": null }, { "creator_type": "author", "first_name": "Dieudonne", "last_name": "van der Meer", "name": null }, { "creator_type": "author", "first_name": "David", "last_name": "Dow", "name": null }, { "creator_type": "author", "first_name": "Carolyn", "last_name": "Buser-Doepner", "name": null }, { "creator_type": "author", "first_name": "Andrea", "last_name": "Bertotti", "name": null }, { "creator_type": "author", "first_name": "Livio", "last_name": "Trusolino", "name": null }, { "creator_type": "author", "first_name": "Euan A.", "last_name": "Stronach", "name": null }, { "creator_type": "author", "first_name": "Julio", "last_name": "Saez-Rodriguez", "name": null }, { "creator_type": "author", "first_name": "Kosuke", "last_name": "Yusa", "name": null }, { "creator_type": "author", "first_name": "Mathew J.", "last_name": "Garnett", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41586-019-1103-9" }, "pmcid": { "normalized": null }, "pmid": { "normalized": null } }, "mesh": [], "publication": { "conference_name": null, "date": "2019-04", "date_precision": "month", "issue": "7753", "normalized_date": "2019-04", "pages": "511-516", "proceedings_title": null, "publisher": "Nature Publishing Group", "title": "Nature", "volume": "568", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "Prioritization of cancer therapeutic targets using CRISPR–Cas9 screens", "url": "https://www.nature.com/articles/s41586-019-1103-9", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Deracemization is a powerful method by which a racemic mixture can be transformed into an excess of one enantiomer with the aid of chiral auxiliaries, but has been applied only to small chiral molecular systems. Here we report a deracemization of a racemic double-stranded spiroborate helicate containing a bisporphyrin unit upon encapsulation of chiral aromatic guests between the bisporphyrin. The chiral guest-included helicate is kinetically stable, existing as a mixture of right- and left-handed double helices, which eventually undergo an inversion of the helicity triggered by water resulting from the water-mediated reversible diastereoselective B-O bond cleavage/reformation of the spiroborate groups, thus producing an optically-active helicate with a high enantioselectivity. Quantum chemical calculations suggest that the stereospecific CH-pi interactions between the porphyrin hydrogen atoms of the helicate and an aromatic pendant group of the chiral guest play a key role in the enhancement of the helical handedness of the helicate.", "classifications": [ { "id": "Hijikata", "label": "Group Hijikata", "parent": "Tsuchiya", "type": "group" }, { "id": "Tsuchiya", "label": "Team Tsuchiya", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Naoki", "last_name": "Ousaka", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Hiroki", "last_name": "Iida", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Iwata", "name": null }, { "creator_type": "author", "first_name": "Shingo", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Yuh", "last_name": "Hijikata", "name": null }, { "creator_type": "author", "first_name": "Stephan", "last_name": "Irle", "name": null }, { "creator_type": "author", "first_name": "Eiji", "last_name": "Yashima", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41467-019-09443-z" }, "pmcid": { "normalized": "PMC6441078" }, "pmid": { "normalized": "30926811" } }, "mesh": [], "publication": { "conference_name": null, "date": "2019 Mar 29", "date_precision": "day", "issue": "1", "normalized_date": "2019-03-29", "pages": "1457", "proceedings_title": null, "publisher": "", "title": "Nature communications", "volume": "10", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "Water-mediated deracemization of a bisporphyrin helicate assisted by diastereoselective encapsulation of chiral guests.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "We investigated the use of narrowband Raman spectra for rapid label-free molecular imaging aimed at cell classification using principal component regression and linear discriminant analysis. In the classification of breast nontumorigenic epithelial and cancer cell lines, the classification accuracies using a spectral range of 100 cm(-1) were equivalent to or better than that with using the fingerprint and high-wavenumber regions. Narrowing the Raman spectral range for analysis allows reduction of the charge-coupled device (CCD) pixels required for spectrum detection, resulting in the improvement of image acquisition speed with adequate classification accuracy. Our measurements revealed that the wavenumber region at 1397-1501 cm(-1) can provide molecular information sufficient for cell classification without causing notable errors in the baseline-correction. A spectral resolution of approximately 9 cm(-1) was found to be sufficient to provide high accuracy in cell classification, which allowed us to apply pixel binning at the CCD readout for further acceleration of the imaging speed. As a result, the acquisition time for a 1200 x 1500 pixels Raman hyperspectral image at 1397-1501 cm(-1) was reduced to 21 min. Under this condition, different cell lines were classified at accuracies higher than 90%. The presented approach will improve throughput of cell and tissue analysis and classification using Raman spectroscopy and extend practical uses of Raman imaging in biology and medicine.", "classifications": [ { "id": "Tanaka", "label": "Group Tanaka", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yasuaki", "last_name": "Kumamoto", "name": null }, { "creator_type": "author", "first_name": "Kentaro", "last_name": "Mochizuki", "name": null }, { "creator_type": "author", "first_name": "Kosuke", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Yoshinori", "last_name": "Harada", "name": null }, { "creator_type": "author", "first_name": "Hideo", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Katsumasa", "last_name": "Fujita", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/acs.jpcb.8b11295" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "30830787" } }, "mesh": [ { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Microscopy", "descriptor_ui": "D008853", "major_topic": false }, { "descriptor": "Principal Component Analysis", "descriptor_ui": "D025341", "major_topic": false }, { "descriptor": "Regression Analysis", "descriptor_ui": "D012044", "major_topic": false }, { "descriptor": "Spectrum Analysis, Raman", "descriptor_ui": "D013059", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019 Mar 28", "date_precision": "day", "issue": "12", "normalized_date": "2019-03-28", "pages": "2654-2661", "proceedings_title": null, "publisher": "", "title": "The journal of physical chemistry. B", "volume": "123", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "High-Throughput Cell Imaging and Classification by Narrowband and Low-Spectral-Resolution Raman Microscopy.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "We previously reported that 8-nitroguanosine 3',5'-cyclic monophosphate (8-nitro-cGMP) is endogenously produced via nitric oxide/reactive oxygen species signaling pathways and it reacts with protein thiol residues to add cGMP structure to proteins through S-guanylation. S-Guanylation occurs on synaptosomal-associated protein 25 (SNAP-25), which is a part of the soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complex that regulates exocytosis. However, the biological relevance of 8-nitro-cGMP in the nervous system remains unclear. Here, we investigated the effects of intracerebroventricular (icv) infusion of 8-nitro-cGMP on mouse brain functions. The results of an open-field test and fear-conditioning task revealed that icv infusion of 8-nitro-cGMP decreased the vertical activity and context-dependent fear memory of mice, which are both associated with the hippocampus. Immunohistochemical analysis revealed increased c-Fos-positive cells in the dentate gyrus in 8-nitro-cGMP-infused mice. Further, biochemical analyses showed that icv infusion of 8-nitro-cGMP increased S-guanylated proteins including SNAP-25 and SNARE complex formation as well as decreased complexes containing complexin, which regulates exocytosis by binding to the SNARE complex, in the hippocampus. These findings suggest that accumulation of 8-nitro-cGMP in the hippocampus affects its functions, including memory, via S-guanylation of hippocampal proteins such as SNAP-25.", "classifications": [ { "id": "Akaike", "label": "Group Akaike", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yusuke", "last_name": "Kishimoto", "name": null }, { "creator_type": "author", "first_name": "Shingo", "last_name": "Kasamatsu", "name": null }, { "creator_type": "author", "first_name": "Shuichi", "last_name": "Yanai", "name": null }, { "creator_type": "author", "first_name": "Shogo", "last_name": "Endo", "name": null }, { "creator_type": "author", "first_name": "Takaaki", "last_name": "Akaike", "name": null }, { "creator_type": "author", "first_name": "Hideshi", "last_name": "Ihara", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.bbrc.2019.01.138" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "30773263" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Brain", "descriptor_ui": "D001921", "major_topic": false }, { "descriptor": "Conditioning, Classical", "descriptor_ui": "D003214", "major_topic": false }, { "descriptor": "Cyclic GMP", "descriptor_ui": "D006152", "major_topic": false }, { "descriptor": "Fear", "descriptor_ui": "D005239", "major_topic": true }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Memory", "descriptor_ui": "D008568", "major_topic": true }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Nitric Oxide", "descriptor_ui": "D009569", "major_topic": false }, { "descriptor": "Reactive Oxygen Species", "descriptor_ui": "D017382", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Synaptosomal-Associated Protein 25", "descriptor_ui": "D050825", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019 Mar 26", "date_precision": "day", "issue": "1", "normalized_date": "2019-03-26", "pages": "141-147", "proceedings_title": null, "publisher": "", "title": "Biochemical and biophysical research communications", "volume": "511", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "8-Nitro-cGMP attenuates context-dependent fear memory in mice.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Brown adipose tissue (BAT) is an attractive therapeutic target for treating obesity and metabolic diseases. Octacosanol is the main component of policosanol, a mixture of very long chain aliphatic alcohols obtained from plants. The current study aimed to investigate the effect of octacosanol and policosanol on high-fat diet (HFD)-induced obesity. Mice were fed on chow, or HFD, with or without octacosanol or policosanol treatment for four weeks. HFD-fed mice showed significantly higher body weight and body fat compared with chow-fed mice. However, mice fed on HFD treated with octacosanol or policosanol (HFDo/p) showed lower body weight gain, body fat gain, insulin resistance and hepatic lipid content. Lower body fat gain after octacosanol or policosanol was associated with increased BAT activity, reduced expression of genes involved in lipogenesis and cholesterol uptake in the liver, and amelioration of white adipose tissue (WAT) inflammation. Moreover, octacosanol and policosanol significantly increased the expression of Ffar4, a gene encoding polyunsaturated fatty acid receptor, which activates BAT thermogenesis. Together, these results suggest that octacosanol and policosanol ameliorate diet-induced obesity and metabolic disorders by increasing BAT activity and improving hepatic lipid metabolism. Thus, these lipids represent promising therapeutic targets for the prevention and treatment of obesity and obesity-related metabolic disorders.", "classifications": [ { "id": "Miyamoto", "label": "Group Miyamoto", "parent": "Wakamoto", "type": "group" }, { "id": "Wakamoto", "label": "Team Wakamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Rahul", "last_name": "Sharma", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Matsuzaka", "name": null }, { "creator_type": "author", "first_name": "Mahesh K.", "last_name": "Kaushik", "name": null }, { "creator_type": "author", "first_name": "Takehito", "last_name": "Sugasawa", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Ohno", "name": null }, { "creator_type": "author", "first_name": "Yunong", "last_name": "Wang", "name": null }, { "creator_type": "author", "first_name": "Kaori", "last_name": "Motomura", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Shimura", "name": null }, { "creator_type": "author", "first_name": "Yuka", "last_name": "Okajima", "name": null }, { "creator_type": "author", "first_name": "Yuhei", "last_name": "Mizunoe", "name": null }, { "creator_type": "author", "first_name": "Yang", "last_name": "Ma", "name": null }, { "creator_type": "author", "first_name": "Zahara M.", "last_name": "Saber", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Iwasaki", "name": null }, { "creator_type": "author", "first_name": "Shigeru", "last_name": "Yatoh", "name": null }, { "creator_type": "author", "first_name": "Hiroaki", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Yuichi", "last_name": "Aita", "name": null }, { "creator_type": "author", "first_name": "Song-Iee", "last_name": "Han", "name": null }, { "creator_type": "author", "first_name": "Yoshinori", "last_name": "Takeuchi", "name": null }, { "creator_type": "author", "first_name": "Naoya", "last_name": "Yahagi", "name": null }, { "creator_type": "author", "first_name": "Takafumi", "last_name": "Miyamoto", "name": null }, { "creator_type": "author", "first_name": "Motohiro", "last_name": "Sekiya", "name": null }, { "creator_type": "author", "first_name": "Yoshimi", "last_name": "Nakagawa", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Shimano", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41598-019-41631-1" }, "pmcid": { "normalized": "PMC6435753" }, "pmid": { "normalized": "30914769" } }, "mesh": [ { "descriptor": "Adipocytes", "descriptor_ui": "D017667", "major_topic": false }, { "descriptor": "Adipose Tissue, Brown", "descriptor_ui": "D002001", "major_topic": false }, { "descriptor": "Adipose Tissue, White", "descriptor_ui": "D052436", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Body Weight", "descriptor_ui": "D001835", "major_topic": false }, { "descriptor": "Diet, High-Fat", "descriptor_ui": "D059305", "major_topic": true }, { "descriptor": "Fatty Alcohols", "descriptor_ui": "D005233", "major_topic": false }, { "descriptor": "Fatty Liver", "descriptor_ui": "D005234", "major_topic": false }, { "descriptor": "Gene Expression Regulation", "descriptor_ui": "D005786", "major_topic": false }, { "descriptor": "Inflammation", "descriptor_ui": "D007249", "major_topic": false }, { "descriptor": "Insulin", "descriptor_ui": "D007328", "major_topic": false }, { "descriptor": "Liver", "descriptor_ui": "D008099", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Metabolic Diseases", "descriptor_ui": "D008659", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Obesity", "descriptor_ui": "D009765", "major_topic": false }, { "descriptor": "Up-Regulation", "descriptor_ui": "D015854", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019 Mar 26", "date_precision": "day", "issue": "1", "normalized_date": "2019-03-26", "pages": "5169", "proceedings_title": null, "publisher": "", "title": "Scientific reports", "volume": "9", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "Octacosanol and policosanol prevent high-fat diet-induced obesity and metabolic disorders by activating brown adipose tissue and improving liver metabolism.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Epithelial sheet integrity is robustly maintained during morphogenesis, which is essential to shape organs and embryos. While maintaining the planar monolayer in three-dimensional space, cells dynamically flow via rearranging their connections between each other. However, little is known about how cells maintain the plane sheet integrity in three-dimensional space and provide cell flow in the in-plane sheet. In this study, using a three-dimensional vertex model, we demonstrate that apical junctional fluctuations allow stable cell rearrangements while ensuring monolayer integrity. In addition to the fluctuations, direction-dependent contraction on the apical cell boundaries, which corresponds to forces from adherens junctions, induces cell flow in a definite direction. We compared the kinematic behaviors of this apical-force-driven cell flow with those of typical cell flow that is driven by forces generated on basal regions and revealed the characteristic differences between them. These differences can be used to distinguish the mechanism of epithelial cell flow observed in experiments, i.e., whether it is apical- or basal-force-driven. Our numerical simulations suggest that cells actively generate fluctuations and use them to regulate both epithelial integrity and plasticity during morphogenesis.", "classifications": [ { "id": "Okuda", "label": "Group Okuda", "parent": "Imayoshi", "type": "group" }, { "id": "Imayoshi", "label": "Team Imayoshi", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Satoru", "last_name": "Okuda", "name": null }, { "creator_type": "author", "first_name": "Erina", "last_name": "Kuranaga", "name": null }, { "creator_type": "author", "first_name": "Katsuhiko", "last_name": "Sato", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.bpj.2019.01.039" }, "pmcid": { "normalized": "PMC6428970" }, "pmid": { "normalized": "30799073" } }, "mesh": [ { "descriptor": "Actomyosin", "descriptor_ui": "D000205", "major_topic": false }, { "descriptor": "Biomechanical Phenomena", "descriptor_ui": "D001696", "major_topic": false }, { "descriptor": "Cell Adhesion", "descriptor_ui": "D002448", "major_topic": false }, { "descriptor": "Epithelium", "descriptor_ui": "D004848", "major_topic": false }, { "descriptor": "Mechanical Phenomena", "descriptor_ui": "D055595", "major_topic": true }, { "descriptor": "Models, Biological", "descriptor_ui": "D008954", "major_topic": true } ], "publication": { "conference_name": null, "date": "2019 Mar 19", "date_precision": "day", "issue": "6", "normalized_date": "2019-03-19", "pages": "1159-1170", "proceedings_title": null, "publisher": "", "title": "Biophysical journal", "volume": "116", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "Apical Junctional Fluctuations Lead to Cell Flow while Maintaining Epithelial Integrity.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Hydropersulfides and related polysulfides have recently become topics of significant interest due to their physiological prevalence and proposed biological functions. Currently, examination of the effects of hydropersulfide treatment on cells is difficult due to their lack of inherent stability with respect to disproportionation. Herein, it is reported that the treatment of a variety of cell types with cysteine trisulfide (also known as thiocystine; Cys-SSS-Cys), results in an increase in intracellular hydropersulfide levels (e.g., cysteine hydropersulfide; Cys-SSH, and glutathione hydropersulfide; GSSH). Thus, Cys-SSS-Cys represents a possible pharmacological agent for examining the effects of hydropersulfides on cell function/viability. It has also been found that cells with increased intracellular hydropersulfide levels can export Cys-SSH into the extracellular media. Interestingly, the Cys-SSH is the major hydropersulfide exported by cells, although GSSH is the predominant intracellular species. The possible implications of cellular export are discussed.", "classifications": [ { "id": "Akaike", "label": "Group Akaike", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Joseph", "last_name": "Lin", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Akiyama", "name": null }, { "creator_type": "author", "first_name": "Iris", "last_name": "Bica", "name": null }, { "creator_type": "author", "first_name": "Faith T.", "last_name": "Long", "name": null }, { "creator_type": "author", "first_name": "Catherine F.", "last_name": "Henderson", "name": null }, { "creator_type": "author", "first_name": "Robert N.", "last_name": "Goddu", "name": null }, { "creator_type": "author", "first_name": "Valeria", "last_name": "Suarez", "name": null }, { "creator_type": "author", "first_name": "Blaine", "last_name": "Baker", "name": null }, { "creator_type": "author", "first_name": "Tomoaki", "last_name": "Ida", "name": null }, { "creator_type": "author", "first_name": "Yasuhiro", "last_name": "Shinkai", "name": null }, { "creator_type": "author", "first_name": "Peter", "last_name": "Nagy", "name": null }, { "creator_type": "author", "first_name": "Takaaki", "last_name": "Akaike", "name": null }, { "creator_type": "author", "first_name": "Jon M.", "last_name": "Fukuto", "name": null }, { "creator_type": "author", "first_name": "Yoshito", "last_name": "Kumagai", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/acs.chemrestox.8b00340" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "30681327" } }, "mesh": [ { "descriptor": "3T3 Cells", "descriptor_ui": "D016475", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "Cell Survival", "descriptor_ui": "D002470", "major_topic": false }, { "descriptor": "Cysteine", "descriptor_ui": "D003545", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Molecular Structure", "descriptor_ui": "D015394", "major_topic": false }, { "descriptor": "Sulfides", "descriptor_ui": "D013440", "major_topic": false }, { "descriptor": "Tetrazolium Salts", "descriptor_ui": "D013778", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019 Mar 18", "date_precision": "day", "issue": "3", "normalized_date": "2019-03-18", "pages": "447-455", "proceedings_title": null, "publisher": "", "title": "Chemical research in toxicology", "volume": "32", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "The Uptake and Release of Polysulfur Cysteine Species by Cells: Physiological and Toxicological Implications.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The PYR/PYL/RCAR protein families have recently emerged as receptors of the phytohormone abscisic acid (ABA, 1), which regulates plant responses to environmental stress. These families have multiple members with different physiological actions, and so selective agonists or antagonists are needed both as tools to elucidate functional differences and as lead compounds for agrochemicals. We previously identified RK460 (rac-3 a) as a PYR1-selective antagonist, and showed that it possesses five stereocenters on a 6,5-cis-bicyclo skeleton. Here, we synthesized all the stereoisomers of RK460 and evaluated their activity towards a panel of receptors. Relative stereochemistry as well as absolute stereochemistry was important for selective action.", "classifications": [ { "id": "Sodeoka", "label": "Group Sodeoka", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yu", "last_name": "Mikame", "name": null }, { "creator_type": "author", "first_name": "Kazuko", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Hashizume", "name": null }, { "creator_type": "author", "first_name": "Go", "last_name": "Hirai", "name": null }, { "creator_type": "author", "first_name": "Kazuo", "last_name": "Nagasawa", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Osada", "name": null }, { "creator_type": "author", "first_name": "Mikiko", "last_name": "Sodeoka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/chem.201806056" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "30589135" } }, "mesh": [ { "descriptor": "Abscisic Acid", "descriptor_ui": "D000040", "major_topic": false }, { "descriptor": "Arabidopsis", "descriptor_ui": "D017360", "major_topic": false }, { "descriptor": "Arabidopsis Proteins", "descriptor_ui": "D029681", "major_topic": false }, { "descriptor": "Bridged Bicyclo Compounds", "descriptor_ui": "D001643", "major_topic": false }, { "descriptor": "Intracellular Signaling Peptides and Proteins", "descriptor_ui": "D047908", "major_topic": false }, { "descriptor": "Membrane Transport Proteins", "descriptor_ui": "D026901", "major_topic": false }, { "descriptor": "Plant Growth Regulators", "descriptor_ui": "D010937", "major_topic": false }, { "descriptor": "Receptors, Cell Surface", "descriptor_ui": "D011956", "major_topic": false }, { "descriptor": "Stereoisomerism", "descriptor_ui": "D013237", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019 Mar 7", "date_precision": "day", "issue": "14", "normalized_date": "2019-03-07", "pages": "3496-3500", "proceedings_title": null, "publisher": "", "title": "Chemistry (Weinheim an der Bergstrasse, Germany)", "volume": "25", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "Synthesis of All Stereoisomers of RK460 and Evaluation of Their Activity and Selectivity as Abscisic Acid Receptor Antagonists.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Intracellular pH is one of the key factors for understanding various biological processes in biological cells. Plasmonic gold and silver nanoparticles (NPs) have been extensively studied for surface-enhanced Raman scattering (SERS) applications for pH sensing as a local pH probe in a living cell. However, the SERS performance of NPs depends on material, size, and shape, which can be controlled by chemical synthesis. Here, we synthesized 18 types of gold and silver NPs with different morphologies such as sphere, rod, flower, star, core/shell, hollow, octahedra, core/satellites, and chainlike aggregates, and quantitatively compared their SERS performance for pH sensing. The SERS intensity from the most commonly utilized SERS probe molecule ( para-mercaptobenzoic acid, p-MBA) for pH sensing was measured at the single nanoparticle level under the same measurement parameters such as low laser power (0.5 mW/mum(2)), short integration time (100 ms) at wavelengths of 405, 488, 532, 584, 676, and 785 nm. In our measurement, the Ag chain, Ag core/satellites, Ag@Au core/satellites, and Au core/satellites nanoassemblies showed efficient pH sensing at the single particle level. By using p-MBA-conjugated Au@Ag core/satellites, we performed time-lapse pH measurements during apoptosis of HeLa cells. These experimental results confirmed that the pH measurement using p-MBA-conjugated Au@Ag core/satellites can be applied for long-term measurements of intracellular pH during cellular events.", "classifications": [ { "id": "Fujita", "label": "Group Fujita", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Zhiqiang", "last_name": "Zhang", "name": null }, { "creator_type": "author", "first_name": "Kazuki", "last_name": "Bando", "name": null }, { "creator_type": "author", "first_name": "Kentaro", "last_name": "Mochizuki", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Taguchi", "name": null }, { "creator_type": "author", "first_name": "Katsumasa", "last_name": "Fujita", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Kawata", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/acs.analchem.8b03276" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "30698014" } }, "mesh": [], "publication": { "conference_name": null, "date": "2019 Mar 5", "date_precision": "day", "issue": "5", "normalized_date": "2019-03-05", "pages": "3254-3262", "proceedings_title": null, "publisher": "", "title": "Analytical chemistry", "volume": "91", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "Quantitative Evaluation of Surface-Enhanced Raman Scattering Nanoparticles for Intracellular pH Sensing at a Single Particle Level.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Atypical teratoid/rhabdoid tumor (AT/RT), which harbors SMARCB1 mutation and exhibits a characteristic histology of rhabdoid cells, has a poor prognosis because of the lack of effective treatments. Here, we establish human SMARCB1-deficient pluripotent stem cells (hPSCs). SMARCB1-deficient hPSC-derived neural progenitor-like cells (NPLCs) efficiently give rise to brain tumors when transplanted into the mouse brain. Notably, activation of an embryonic stem cell (ESC)-like signature confers a rhabdoid histology in SMARCB1-deficient NPLC-derived tumors and causes a poor prognosis. Consistently, we find the activation of the ESC-like gene expression signature and an ESC-like DNA methylation landscape in clinical specimens of AT/RT. Finally, we identify candidate genes that maintain the activation of the ESC-like signature and the growth of AT/RT cells. Collectively, SMARCB1-deficient hPSCs offer the human models for AT/RT, which uncover the role of the activated ESC-like signature in the poor prognosis and unique histology of AT/RT.", "classifications": [ { "id": "Yamamoto", "label": "Group Yamamoto", "parent": "Toyoshima", "type": "group" }, { "id": "Toyoshima", "label": "Team Toyoshima", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yukinori", "last_name": "Terada", "name": null }, { "creator_type": "author", "first_name": "Norihide", "last_name": "Jo", "name": null }, { "creator_type": "author", "first_name": "Yoshiki", "last_name": "Arakawa", "name": null }, { "creator_type": "author", "first_name": "Megumi", "last_name": "Sakakura", "name": null }, { "creator_type": "author", "first_name": "Yosuke", "last_name": "Yamada", "name": null }, { "creator_type": "author", "first_name": "Tomoyo", "last_name": "Ukai", "name": null }, { "creator_type": "author", "first_name": "Mio", "last_name": "Kabata", "name": null }, { "creator_type": "author", "first_name": "Kanae", "last_name": "Mitsunaga", "name": null }, { "creator_type": "author", "first_name": "Yohei", "last_name": "Mineharu", "name": null }, { "creator_type": "author", "first_name": "Sho", "last_name": "Ohta", "name": null }, { "creator_type": "author", "first_name": "Masato", "last_name": "Nakagawa", "name": null }, { "creator_type": "author", "first_name": "Susumu", "last_name": "Miyamoto", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Yasuhiro", "last_name": "Yamada", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.celrep.2019.02.009" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "30840885" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Culture Techniques", "descriptor_ui": "D018929", "major_topic": false }, { "descriptor": "Embryonic Stem Cells", "descriptor_ui": "D053595", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Pluripotent Stem Cells", "descriptor_ui": "D039904", "major_topic": false }, { "descriptor": "Rhabdoid Tumor", "descriptor_ui": "D018335", "major_topic": false }, { "descriptor": "Transfection", "descriptor_ui": "D014162", "major_topic": false }, { "descriptor": "Xenograft Model Antitumor Assays", "descriptor_ui": "D023041", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019 Mar 5", "date_precision": "day", "issue": "10", "normalized_date": "2019-03-05", "pages": "2608-2621.e6", "proceedings_title": null, "publisher": "", "title": "Cell reports", "volume": "26", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "Human Pluripotent Stem Cell-Derived Tumor Model Uncovers the Embryonic Stem Cell Signature as a Key Driver in Atypical Teratoid/Rhabdoid Tumor.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Despite their central role in multicellular organization, navigation rules that dictate cell rearrangement remain largely undefined. Contact between neighboring cells and diffusive attractant molecules are two of the major determinants of tissue-level patterning; however, in most cases, molecular and developmental complexity hinders one from decoding the exact governing rules of individual cell movement. A primordial example of tissue patterning by cell rearrangement is found in the social amoeba Dictyostelium discoideum where the organizing center or the \"tip\" self-organizes as a result of sorting of differentiating prestalk and prespore cells. By employing microfluidics and microsphere-based manipulation of navigational cues at the single-cell level, here we uncovered a previously overlooked mode of Dictyostelium cell migration that is strictly directed by cell-cell contact. The cell-cell contact signal is mediated by E-set Ig-like domain-containing heterophilic adhesion molecules TgrB1/TgrC1 that act in trans to induce plasma membrane recruitment of the SCAR complex and formation of dendritic actin networks, and the resulting cell protrusion competes with those induced by chemoattractant cAMP. Furthermore, we demonstrate that both prestalk and prespore cells can protrude toward the contact signal as well as to chemotax toward cAMP; however, when given both signals, prestalk cells orient toward the chemoattractant, whereas prespore cells choose the contact signal. These data suggest a model of cell sorting by competing juxtacrine and diffusive cues, each with potential to drive its own mode of collective cell migration.", "classifications": [ { "id": "Sawai", "label": "Group Sawai", "parent": "Sawai", "type": "group" }, { "id": "Sawai", "label": "Team Sawai", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Taihei", "last_name": "Fujimori", "name": null }, { "creator_type": "author", "first_name": "Akihiko", "last_name": "Nakajima", "name": null }, { "creator_type": "author", "first_name": "Nao", "last_name": "Shimada", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Sawai", "name": null } ], "identifiers": { "doi": { "normalized": "10.1073/pnas.1815063116" }, "pmcid": { "normalized": "PMC6410881" }, "pmid": { "normalized": "30782791" } }, "mesh": [ { "descriptor": "Actins", "descriptor_ui": "D000199", "major_topic": false }, { "descriptor": "Cell Aggregation", "descriptor_ui": "D002449", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Cell Movement", "descriptor_ui": "D002465", "major_topic": false }, { "descriptor": "Chemotaxis", "descriptor_ui": "D002633", "major_topic": false }, { "descriptor": "Cyclic AMP", "descriptor_ui": "D000242", "major_topic": false }, { "descriptor": "Dictyostelium", "descriptor_ui": "D004023", "major_topic": false }, { "descriptor": "Diffusion", "descriptor_ui": "D004058", "major_topic": false }, { "descriptor": "Locomotion", "descriptor_ui": "D008124", "major_topic": false }, { "descriptor": "Microfluidics", "descriptor_ui": "D044085", "major_topic": false }, { "descriptor": "Protozoan Proteins", "descriptor_ui": "D015800", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019 Mar 5", "date_precision": "day", "issue": "10", "normalized_date": "2019-03-05", "pages": "4291-4296", "proceedings_title": null, "publisher": "", "title": "Proceedings of the National Academy of Sciences of the United States of America", "volume": "116", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "Tissue self-organization based on collective cell migration by contact activation of locomotion and chemotaxis.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Orexin (ORX) neurons in the hypothalamus send their axons to arousal-promoting areas. We have previously shown that glutamatergic neurons in the lateral parabrachial nucleus (LPB) innervate ORX neurons. In this study, we examined potential pathways from the LPB to ORX neurons projecting to arousal-promoting areas in the brainstem by a combination of tract-tracing techniques in male Wistar rats. We injected the anterograde tracer biotinylated dextranamine (BDA) into the LPB and the retrograde tracer cholera toxin B subunit (CTb) into the ventral tegmental area, dorsal raphe nucleus, pedunculopontine tegmental nucleus, laterodorsal tegmental area, or locus coeruleus (LC). We then analyzed the BDA-labeled fibers and ORX-immunoreactive neurons in the hypothalamus. We found that double-labeled ORX and CTb neurons were the most abundant after CTb was injected into the LC. We also observed prominently overlapping distribution of BDA-labeled fibers, arising from neurons located in the lateral-most part of the dorsomedial nucleus and adjacent dorsal perifornical area. In these areas, we confirmed by confocal microscopy that BDA-labeled synaptophysin-immunoreactive axon terminals were in contiguity with cell bodies and dendrites of CTb-labeled ORX-immunoreactive neurons. These results suggest that the LPB innervates arousal-promoting areas via ORX neurons and is likely to promote arousal responses to stimuli.", "classifications": [ { "id": "Yokota", "label": "Group Yokota", "parent": "Enomoto", "type": "group" }, { "id": "Enomoto", "label": "Team Enomoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yosuke", "last_name": "Arima", "name": null }, { "creator_type": "author", "first_name": "Shigefumi", "last_name": "Yokota", "name": null }, { "creator_type": "author", "first_name": "Masashi", "last_name": "Fujitani", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41598-019-39063-y" }, "pmcid": { "normalized": "PMC6391479" }, "pmid": { "normalized": "30808976" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Arousal", "descriptor_ui": "D001143", "major_topic": true }, { "descriptor": "Brain Stem", "descriptor_ui": "D001933", "major_topic": false }, { "descriptor": "Hypothalamus", "descriptor_ui": "D007031", "major_topic": true }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Neural Pathways", "descriptor_ui": "D009434", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": true }, { "descriptor": "Orexins", "descriptor_ui": "D000068797", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Rats, Wistar", "descriptor_ui": "D017208", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019 Feb 26", "date_precision": "day", "issue": "1", "normalized_date": "2019-02-26", "pages": "2830", "proceedings_title": null, "publisher": "", "title": "Scientific reports", "volume": "9", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "Lateral parabrachial neurons innervate orexin neurons projecting to brainstem arousal areas in the rat.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "A class of translation inhibitors, exemplified by the natural product rocaglamide A (RocA), isolated from Aglaia genus plants, exhibits antitumor activity by clamping eukaryotic translation initiation factor 4A (eIF4A) onto polypurine sequences in mRNAs. This unusual inhibitory mechanism raises the question of how the drug imposes sequence selectivity onto a general translation factor. Here, we determined the crystal structure of the human eIF4A1ATP analogRocApolypurine RNA complex. RocA targets the \"bi-molecular cavity\" formed characteristically by eIF4A1 and a sharply bent pair of consecutive purines in the RNA. Natural amino acid substitutions found in Aglaia eIF4As changed the cavity shape, leading to RocA resistance. This study provides an example of an RNA-sequence-selective interfacial inhibitor fitting into the space shaped cooperatively by protein and RNA with specific sequences.", "classifications": [ { "id": "Sodeoka", "label": "Group Sodeoka", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Shintaro", "last_name": "Iwasaki", "name": null }, { "creator_type": "author", "first_name": "Wakana", "last_name": "Iwasaki", "name": null }, { "creator_type": "author", "first_name": "Mari", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Ayako", "last_name": "Sakamoto", "name": null }, { "creator_type": "author", "first_name": "Chiduru", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Yuichi", "last_name": "Shichino", "name": null }, { "creator_type": "author", "first_name": "Stephen N.", "last_name": "Floor", "name": null }, { "creator_type": "author", "first_name": "Koichi", "last_name": "Fujiwara", "name": null }, { "creator_type": "author", "first_name": "Mari", "last_name": "Mito", "name": null }, { "creator_type": "author", "first_name": "Kosuke", "last_name": "Dodo", "name": null }, { "creator_type": "author", "first_name": "Mikiko", "last_name": "Sodeoka", "name": null }, { "creator_type": "author", "first_name": "Hiroaki", "last_name": "Imataka", "name": null }, { "creator_type": "author", "first_name": "Teruki", "last_name": "Honma", "name": null }, { "creator_type": "author", "first_name": "Kaori", "last_name": "Fukuzawa", "name": null }, { "creator_type": "author", "first_name": "Takuhiro", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Nicholas T.", "last_name": "Ingolia", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.molcel.2018.11.026" }, "pmcid": { "normalized": "PMC6386617" }, "pmid": { "normalized": "30595437" } }, "mesh": [ { "descriptor": "Adenylyl Imidodiphosphate", "descriptor_ui": "D000266", "major_topic": false }, { "descriptor": "Aglaia", "descriptor_ui": "D031602", "major_topic": false }, { "descriptor": "Amino Acid Substitution", "descriptor_ui": "D019943", "major_topic": false }, { "descriptor": "Benzofurans", "descriptor_ui": "D001572", "major_topic": false }, { "descriptor": "Binding Sites", "descriptor_ui": "D001665", "major_topic": false }, { "descriptor": "Drug Resistance", "descriptor_ui": "D004351", "major_topic": false }, { "descriptor": "Eukaryotic Initiation Factor-4A", "descriptor_ui": "D039601", "major_topic": false }, { "descriptor": "HEK293 Cells", "descriptor_ui": "D057809", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Models, Molecular", "descriptor_ui": "D008958", "major_topic": false }, { "descriptor": "Molecular Structure", "descriptor_ui": "D015394", "major_topic": false }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": false }, { "descriptor": "Plant Proteins", "descriptor_ui": "D010940", "major_topic": false }, { "descriptor": "Protein Binding", "descriptor_ui": "D011485", "major_topic": false }, { "descriptor": "Protein Biosynthesis", "descriptor_ui": "D014176", "major_topic": true }, { "descriptor": "Protein Interaction Domains and Motifs", "descriptor_ui": "D054730", "major_topic": false }, { "descriptor": "Protein Synthesis Inhibitors", "descriptor_ui": "D011500", "major_topic": false }, { "descriptor": "Ribosomes", "descriptor_ui": "D012270", "major_topic": false }, { "descriptor": "RNA", "descriptor_ui": "D012313", "major_topic": false }, { "descriptor": "Structure-Activity Relationship", "descriptor_ui": "D013329", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019 Feb 21", "date_precision": "day", "issue": "4", "normalized_date": "2019-02-21", "pages": "738-748.e9", "proceedings_title": null, "publisher": "", "title": "Molecular cell", "volume": "73", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "The Translation Inhibitor Rocaglamide Targets a Bimolecular Cavity between eIF4A and Polypurine RNA.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Herein, we developed isostructural metal-organic frameworks (MOFs) [Cu1-xPdx(SiF6)(bpy)2] (bpy: 4,4'-bipyridine) (SIFSIX-1-CuPd-3, -5 and -10) containing open metal sites using a partial metal-replacement approach. Starting from the SIFSIX-1-Cu-type MOF, some of the Cu2+ ions having octahedral geometry were successfully replaced with Pd2+ ions having square planar geometry in different ratios, while the framework structure was maintained. The results showed that gas adsorption properties of SIFSIX-1-Cu-type MOFs can be tuned via partial metal replacement.", "classifications": [ { "id": "Hijikata", "label": "Group Hijikata", "parent": "Tsuchiya", "type": "group" }, { "id": "Tsuchiya", "label": "Team Tsuchiya", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yuki", "last_name": "Harada", "name": null }, { "creator_type": "author", "first_name": "Yuh", "last_name": "Hijikata", "name": null }, { "creator_type": "author", "first_name": "Shinpei", "last_name": "Kusaka", "name": null }, { "creator_type": "author", "first_name": "Akihiro", "last_name": "Hori", "name": null }, { "creator_type": "author", "first_name": "Yunsheng", "last_name": "Ma", "name": null }, { "creator_type": "author", "first_name": "Ryotaro", "last_name": "Matsuda", "name": null } ], "identifiers": { "doi": { "normalized": "10.1039/c8dt04218g" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "30570640" } }, "mesh": [], "publication": { "conference_name": null, "date": "2019 Feb 19", "date_precision": "day", "issue": "8", "normalized_date": "2019-02-19", "pages": "2545-2548", "proceedings_title": null, "publisher": "", "title": "Dalton transactions (Cambridge, England : 2003)", "volume": "48", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "Creation of MOFs with open metal sites by partial replacement of metal ions with different coordination numbers.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The development of a universal influenza vaccine that can provide a robust and long-lasting protection against a broader range of influenza virus strains is a global public health priority. One approach to improve vaccine efficacy is to use an adjuvant to boost immune responses to the target antigens; nevertheless, the role of adjuvants in the context of influenza vaccines is not fully understood. We have previously developed the K3-schizophyllan (SPG) adjuvant, which is composed of nanoparticulated oligodeoxynucleotides K3, a TLR9 agonist, with SPG, a non-agonistic β-glucan ligand of Dectin-1. In this study, K3-SPG given with conventional influenza hemagglutinin (HA) split vaccine (K3-SPG HA) conferred protection against antigenically mismatched heterologous virus challenge. While K3-SPG HA elicited robust cross-reactive HA-specific IgG2c and CD8 T-cell responses, CD8 T-cell depletion had no impact on this cross-protection. In contrast, K3-SPG HA was not able to confer protection against heterologous virus challenge in FcRγ-deficient mice. Our results indicated that FcγR-mediated antibody responses induced by the HA antigen and K3-SPG adjuvant were important for potent protection against antigenically mismatched influenza virus infection. Thus, we demonstrated that the K3-SPG-adjuvanted vaccine strategy broadens protective immunity against influenza and provides a basis for the development of next-generation influenza vaccines.", "classifications": [ { "id": "Yamamoto", "label": "Group Yamamoto", "parent": "Toyoshima", "type": "group" }, { "id": "Toyoshima", "label": "Team Toyoshima", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Takuya", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Yuji", "last_name": "Masuta", "name": null }, { "creator_type": "author", "first_name": "Masatoshi", "last_name": "Momota", "name": null }, { "creator_type": "author", "first_name": "Masaru", "last_name": "Kanekiyo", "name": null }, { "creator_type": "author", "first_name": "Tomohiro", "last_name": "Kanuma", "name": null }, { "creator_type": "author", "first_name": "Shoukichi", "last_name": "Takahama", "name": null }, { "creator_type": "author", "first_name": "Eiko", "last_name": "Moriishi", "name": null }, { "creator_type": "author", "first_name": "Yasuhiro", "last_name": "Yasutomi", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Barney S.", "last_name": "Graham", "name": null }, { "creator_type": "author", "first_name": "Yoshimasa", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Ken J.", "last_name": "Ishii", "name": null } ], "identifiers": { "doi": { "normalized": "10.1093/intimm/dxy069" }, "pmcid": { "normalized": "PMC6599278" }, "pmid": { "normalized": "30535055" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Hemagglutinins, Viral", "descriptor_ui": "D006389", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Influenza Vaccines", "descriptor_ui": "D007252", "major_topic": false }, { "descriptor": "Influenza, Human", "descriptor_ui": "D007251", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Nanoparticles", "descriptor_ui": "D053758", "major_topic": false }, { "descriptor": "Orthomyxoviridae Infections", "descriptor_ui": "D009976", "major_topic": false }, { "descriptor": "Receptors, Fc", "descriptor_ui": "D011961", "major_topic": false }, { "descriptor": "Toll-Like Receptor 9", "descriptor_ui": "D051217", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019 Feb 15", "date_precision": "day", "issue": "2", "normalized_date": "2019-02-15", "pages": "81-90", "proceedings_title": null, "publisher": "", "title": "International immunology", "volume": "31", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "A unique nanoparticulate TLR9 agonist enables a HA split vaccine to confer FcγR-mediated protection against heterologous lethal influenza virus infection.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Stomatal movement mediates plant gas exchange, which is essential for photosynthesis and transpiration. Stomatal opening and closing are accomplished by a significant increase and decrease in guard cell volume, respectively. Because shuttle transport of ions and water occurs between guard cells and larger neighboring epidermal cells during stomatal movement, the spaced distribution of plant stomata is considered an optimal distribution for stomatal movement. Experimental systems for perturbing the spaced pattern of stomata are useful to examine the spacing pattern's significance. Several key genes associated with the spaced stomatal distribution have been identified, and clustered stomata can be experimentally induced by altering these genes. Alternatively, clustered stomata can be also induced by exogenous treatments without genetic modification. In this article, we describe a simple induction system for clustered stomata in Arabidopsis thaliana seedlings by immersion treatment with a sucrose-containing medium solution. Our method is easy and directly applicable to transgenic or mutant lines. Larger chloroplasts are presented as a cell biological hallmark of sucrose-induced clustered guard cells. In addition, a representative confocal microscopic image of cortical microtubules is shown as an example of intracellular observation of clustered guard cells. The radial orientation of cortical microtubules is maintained in clustered guard cells as in spaced guard cells in control conditions.", "classifications": [ { "id": "Higaki", "label": "Group Higaki", "parent": "Ueda", "type": "group" }, { "id": "Ueda", "label": "Team Ueda", "type": "team" } ], "creators": [ { "creator_type": "contributor", "first_name": "Kae", "last_name": "Akita", "name": null }, { "creator_type": "contributor", "first_name": "Takumi", "last_name": "Higaki", "name": null } ], "identifiers": { "doi": { "normalized": "10.3791/58951" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "30829333" } }, "mesh": [ { "descriptor": "Arabidopsis", "descriptor_ui": "D017360", "major_topic": false }, { "descriptor": "Arabidopsis Proteins", "descriptor_ui": "D029681", "major_topic": false }, { "descriptor": "Plant Stomata", "descriptor_ui": "D054046", "major_topic": false }, { "descriptor": "Seedlings", "descriptor_ui": "D036226", "major_topic": false }, { "descriptor": "Sugars", "descriptor_ui": "D000073893", "major_topic": false }, { "descriptor": "Water", "descriptor_ui": "D014867", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019 Feb 15", "date_precision": "day", "issue": "144", "normalized_date": "2019-02-15", "pages": "", "proceedings_title": null, "publisher": "", "title": "", "volume": "", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "An Induction System for Clustered Stomata by Sugar Solution Immersion Treatment in Arabidopsis thaliana Seedlings.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Field studies have shown that plants growing next to herbivore-infested plants acquire higher resistance to herbivore damage. This increased resistance is partly due to regulation of plant gene expression by volatile organic compounds (VOCs) released by plants that sense environmental challenges such as herbivores. The molecular basis for VOC sensing in plants, however, is poorly understood. Here, we report the identification of TOPLESS-like proteins (TPLs) that have VOC-binding activity and are involved in VOC sensing in tobacco. While screening for volatiles that induce stress-responsive gene expression in tobacco BY-2 cells and tobacco plants, we found that some sesquiterpenes induce the expression of stress-responsive genes. These results provided evidence that plants sense these VOCs and motivated us to analyze the mechanisms underlying volatile sensing using tobacco as a model system. Using a pulldown assay with caryophyllene derivative-linked beads, we identified TPLs as transcriptional co-repressors that bind volatile caryophyllene analogs. Overexpression of TPLs in cultured BY-2 cells or tobacco leaves reduced caryophyllene-induced gene expression, indicating that TPLs are involved in the responses to caryophyllene analogs in tobacco. We propose that unlike animals, which use membrane receptors for sensing odorants, a transcriptional co-repressor plays a role in sensing and mediating VOC signals in plant cells.", "classifications": [ { "id": "Higaki", "label": "Group Higaki", "parent": "Ueda", "type": "group" }, { "id": "Ueda", "label": "Team Ueda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Ayumi", "last_name": "Nagashima", "name": null }, { "creator_type": "author", "first_name": "Takumi", "last_name": "Higaki", "name": null }, { "creator_type": "author", "first_name": "Takao", "last_name": "Koeduka", "name": null }, { "creator_type": "author", "first_name": "Ken", "last_name": "Ishigami", "name": null }, { "creator_type": "author", "first_name": "Satoko", "last_name": "Hosokawa", "name": null }, { "creator_type": "author", "first_name": "Hidenori", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Matsui", "name": null }, { "creator_type": "author", "first_name": "Seiichiro", "last_name": "Hasezawa", "name": null }, { "creator_type": "author", "first_name": "Kazushige", "last_name": "Touhara", "name": null } ], "identifiers": { "doi": { "normalized": "10.1074/jbc.ra118.005843" }, "pmcid": { "normalized": "PMC6378981" }, "pmid": { "normalized": "30593507" } }, "mesh": [ { "descriptor": "Gene Expression Regulation, Plant", "descriptor_ui": "D018506", "major_topic": false }, { "descriptor": "Nicotiana", "descriptor_ui": "D014026", "major_topic": true }, { "descriptor": "Plant Cells", "descriptor_ui": "D059828", "major_topic": false }, { "descriptor": "Plant Proteins", "descriptor_ui": "D010940", "major_topic": true }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Stress, Physiological", "descriptor_ui": "D013312", "major_topic": false }, { "descriptor": "Transcription, Genetic", "descriptor_ui": "D014158", "major_topic": false }, { "descriptor": "Volatile Organic Compounds", "descriptor_ui": "D055549", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019 Feb 15", "date_precision": "day", "issue": "7", "normalized_date": "2019-02-15", "pages": "2256-2266", "proceedings_title": null, "publisher": "", "title": "The Journal of biological chemistry", "volume": "294", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "Transcriptional regulators involved in responses to volatile organic compounds in plants.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "During somatic cell reprogramming to induced pluripotent stem cells (iPSCs), fibroblasts undergo dynamic molecular changes, including a mesenchymal-to-epithelial transition (MET) and gain of pluripotency; processes that are influenced by Yamanaka factor stoichiometry. For example, in early reprogramming, high KLF4 levels are correlated with the induction of functionally undefined, transiently expressed MET genes. Here, we identified the cell-surface protein TROP2 as a marker for cells with transient MET induction in the high-KLF4 condition. We observed the emergence of cells expressing the pluripotency marker SSEA-1(+) mainly from within the TROP2(+) fraction. Using TROP2 as a marker in CRISPR/Cas9-mediated candidate screening of MET genes, we identified the transcription factor OVOL1 as a potential regulator of an alternative epithelial cell fate characterized by the expression of non-iPSC MET genes and low cell proliferation. Our study sheds light on how reprogramming factor stoichiometry alters the spectrum of intermediate cell fates, ultimately influencing reprogramming outcomes.", "classifications": [ { "id": "Yamamoto", "label": "Group Yamamoto", "parent": "Toyoshima", "type": "group" }, { "id": "Toyoshima", "label": "Team Toyoshima", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Harunobu", "last_name": "Kagawa", "name": null }, { "creator_type": "author", "first_name": "Ren", "last_name": "Shimamoto", "name": null }, { "creator_type": "author", "first_name": "Shin-Il", "last_name": "Kim", "name": null }, { "creator_type": "author", "first_name": "Fabian", "last_name": "Oceguera-Yanez", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Timm", "last_name": "Schroeder", "name": null }, { "creator_type": "author", "first_name": "Knut", "last_name": "Woltjen", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.stemcr.2018.12.008" }, "pmcid": { "normalized": "PMC6372973" }, "pmid": { "normalized": "30639212" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Biomarkers", "descriptor_ui": "D015415", "major_topic": false }, { "descriptor": "Cell Adhesion Molecules", "descriptor_ui": "D015815", "major_topic": false }, { "descriptor": "Cell Proliferation", "descriptor_ui": "D049109", "major_topic": false }, { "descriptor": "Cellular Reprogramming", "descriptor_ui": "D065150", "major_topic": false }, { "descriptor": "CRISPR-Cas Systems", "descriptor_ui": "D064113", "major_topic": false }, { "descriptor": "DNA-Binding Proteins", "descriptor_ui": "D004268", "major_topic": false }, { "descriptor": "Epithelial Cells", "descriptor_ui": "D004847", "major_topic": false }, { "descriptor": "Epithelial-Mesenchymal Transition", "descriptor_ui": "D058750", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Fibroblasts", "descriptor_ui": "D005347", "major_topic": false }, { "descriptor": "Gene Expression Regulation", "descriptor_ui": "D005786", "major_topic": false }, { "descriptor": "Induced Pluripotent Stem Cells", "descriptor_ui": "D057026", "major_topic": false }, { "descriptor": "Kruppel-Like Factor 4", "descriptor_ui": "D000090062", "major_topic": false }, { "descriptor": "Kruppel-Like Transcription Factors", "descriptor_ui": "D051741", "major_topic": false }, { "descriptor": "Lewis X Antigen", "descriptor_ui": "D016256", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Transcription Factors", "descriptor_ui": "D014157", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019 Feb 12", "date_precision": "day", "issue": "2", "normalized_date": "2019-02-12", "pages": "319-332", "proceedings_title": null, "publisher": "", "title": "Stem cell reports", "volume": "12", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "OVOL1 Influences the Determination and Expansion of iPSC Reprogramming Intermediates.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Recent technical improvements in single-cell RNA sequencing (scRNA-seq) have enabled massively parallel profiling of transcriptomes, thereby promoting large-scale studies encompassing a wide range of cell types of multicellular organisms. With this background, we propose CellFishing.jl, a new method for searching atlas-scale datasets for similar cells and detecting noteworthy genes of query cells with high accuracy and throughput. Using multiple scRNA-seq datasets, we validate that our method demonstrates comparable accuracy to and is markedly faster than the state-of-the-art software. Moreover, CellFishing.jl is scalable to more than one million cells, and the throughput of the search is approximately 1600 cells per second.", "classifications": [ { "id": "Nikaido", "label": "Group Nikaido", "parent": "Fujiwara", "type": "group" }, { "id": "Fujiwara", "label": "Team Fujiwara", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Kenta", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Koki", "last_name": "Tsuyuzaki", "name": null }, { "creator_type": "author", "first_name": "Kentaro", "last_name": "Shimizu", "name": null }, { "creator_type": "author", "first_name": "Itoshi", "last_name": "Nikaido", "name": null } ], "identifiers": { "doi": { "normalized": "10.1186/s13059-019-1639-x" }, "pmcid": { "normalized": "PMC6371477" }, "pmid": { "normalized": "30744683" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Genomics", "descriptor_ui": "D023281", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Sequence Analysis, RNA", "descriptor_ui": "D017423", "major_topic": true }, { "descriptor": "Single-Cell Analysis", "descriptor_ui": "D059010", "major_topic": true }, { "descriptor": "Software", "descriptor_ui": "D012984", "major_topic": true } ], "publication": { "conference_name": null, "date": "2019 Feb 11", "date_precision": "day", "issue": "1", "normalized_date": "2019-02-11", "pages": "31", "proceedings_title": null, "publisher": "", "title": "Genome biology", "volume": "20", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "CellFishing.jl: an ultrafast and scalable cell search method for single-cell RNA sequencing.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "During embryogenesis, exocrine and endocrine pancreatic tissues are formed in distinct regions within the branched ductal structure in mice. We previously reported that exocrine-specific inactivation of Pdx1 by Elastase-Cre caused not only hypoplastic exocrine formation but also substantial endocrine defects resulting in diabetic phenotype, indicating the existence of an exocrine-driven factor(s) that regulates proper endocrine development. In this study, we identified Trefoil Factor 2 (TFF2) as an exocrine gene expressed from embryonic day 16.5 to adulthood in normal mice but significantly less in our Pdx1 mutants. Using in vitro explant culture of embryonic pancreatic tissue, we demonstrated that TFF2 prevented the apoptosis of insulin-producing cells but that antagonizing CXCR4, a known TFF2 receptor, suppressed this anti-apoptotic effect in the mutants. Furthermore, the antagonist in normal pancreatic tissue accelerated the apoptosis of insulin-producing cells, indicating that the TFF2/CXCR4 axis maintains embryonic insulin-producing cells in normal development. TFF2 also suppressed the apoptosis of Nkx6.1+ endocrine precursors in mutant pancreata, but this effect was unperturbed by the CXCR4 antagonist, suggesting the existence of an unknown receptor for TFF2. These findings suggest TFF2 is a novel exocrine factor that supports the survival of endocrine cells in the multiple stages of organogenesis through distinct receptors.", "classifications": [ { "id": "Yamamoto", "label": "Group Yamamoto", "parent": "Toyoshima", "type": "group" }, { "id": "Toyoshima", "label": "Team Toyoshima", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Koji", "last_name": "Hirata", "name": null }, { "creator_type": "author", "first_name": "Sota", "last_name": "Kodama", "name": null }, { "creator_type": "author", "first_name": "Yasuhiro", "last_name": "Nakano", "name": null }, { "creator_type": "author", "first_name": "Yasuko", "last_name": "Minaki-Nakagawa", "name": null }, { "creator_type": "author", "first_name": "Yoshiki", "last_name": "Aoyama", "name": null }, { "creator_type": "author", "first_name": "Morito", "last_name": "Sakikubo", "name": null }, { "creator_type": "author", "first_name": "Toshihiko", "last_name": "Goto", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Toshihiko", "last_name": "Masui", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Shinji", "last_name": "Uemoto", "name": null }, { "creator_type": "author", "first_name": "Yoshiya", "last_name": "Kawaguchi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41598-018-38062-9" }, "pmcid": { "normalized": "PMC6367380" }, "pmid": { "normalized": "30733468" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Apoptosis", "descriptor_ui": "D017209", "major_topic": false }, { "descriptor": "Cell Lineage", "descriptor_ui": "D019070", "major_topic": false }, { "descriptor": "Gene Expression Regulation, Developmental", "descriptor_ui": "D018507", "major_topic": false }, { "descriptor": "Homeodomain Proteins", "descriptor_ui": "D018398", "major_topic": false }, { "descriptor": "Insulin", "descriptor_ui": "D007328", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Organogenesis", "descriptor_ui": "D038081", "major_topic": false }, { "descriptor": "Pancreas", "descriptor_ui": "D010179", "major_topic": false }, { "descriptor": "Receptors, CXCR4", "descriptor_ui": "D019718", "major_topic": false }, { "descriptor": "Trans-Activators", "descriptor_ui": "D015534", "major_topic": false }, { "descriptor": "Trefoil Factor-2", "descriptor_ui": "D000071164", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019 Feb 7", "date_precision": "day", "issue": "1", "normalized_date": "2019-02-07", "pages": "1636", "proceedings_title": null, "publisher": "", "title": "Scientific reports", "volume": "9", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "Exocrine tissue-driven TFF2 prevents apoptotic cell death of endocrine lineage during pancreas organogenesis.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "T helper type 2 (Th2) cells are important regulators of mammalian adaptive immunity and have relevance for infection, autoimmunity, and tumor immunology. Using a newly developed, genome-wide retroviral CRISPR knockout (KO) library, combined with RNA-seq, ATAC-seq, and ChIP-seq, we have dissected the regulatory circuitry governing activation and differentiation of these cells. Our experiments distinguish cell activation versus differentiation in a quantitative framework. We demonstrate that these two processes are tightly coupled and are jointly controlled by many transcription factors, metabolic genes, and cytokine/receptor pairs. There are only a small number of genes regulating differentiation without any role in activation. By combining biochemical and genetic data, we provide an atlas for Th2 differentiation, validating known regulators and identifying factors, such as Pparg and Bhlhe40, as part of the core regulatory network governing Th2 helper cell fates.", "classifications": [ { "id": "Yusa", "label": "Group Yusa", "parent": "Eiraku", "type": "group" }, { "id": "Eiraku", "label": "Team Eiraku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Johan", "last_name": "Henriksson", "name": null }, { "creator_type": "author", "first_name": "Xi", "last_name": "Chen", "name": null }, { "creator_type": "author", "first_name": "Tomas", "last_name": "Gomes", "name": null }, { "creator_type": "author", "first_name": "Ubaid", "last_name": "Ullah", "name": null }, { "creator_type": "author", "first_name": "Kerstin B.", "last_name": "Meyer", "name": null }, { "creator_type": "author", "first_name": "Ricardo", "last_name": "Miragaia", "name": null }, { "creator_type": "author", "first_name": "Graham", "last_name": "Duddy", "name": null }, { "creator_type": "author", "first_name": "Jhuma", "last_name": "Pramanik", "name": null }, { "creator_type": "author", "first_name": "Kosuke", "last_name": "Yusa", "name": null }, { "creator_type": "author", "first_name": "Riitta", "last_name": "Lahesmaa", "name": null }, { "creator_type": "author", "first_name": "Sarah A.", "last_name": "Teichmann", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.cell.2018.11.044" }, "pmcid": { "normalized": "PMC6370901" }, "pmid": { "normalized": "30639098" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Chromatin", "descriptor_ui": "D002843", "major_topic": false }, { "descriptor": "Clustered Regularly Interspaced Short Palindromic Repeats", "descriptor_ui": "D064112", "major_topic": false }, { "descriptor": "CRISPR-Cas Systems", "descriptor_ui": "D064113", "major_topic": false }, { "descriptor": "Genome", "descriptor_ui": "D016678", "major_topic": false }, { "descriptor": "High-Throughput Nucleotide Sequencing", "descriptor_ui": "D059014", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Lymphocyte Activation", "descriptor_ui": "D008213", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Receptor Cross-Talk", "descriptor_ui": "D020239", "major_topic": false }, { "descriptor": "T-Lymphocytes, Helper-Inducer", "descriptor_ui": "D006377", "major_topic": false }, { "descriptor": "Th2 Cells", "descriptor_ui": "D018418", "major_topic": false }, { "descriptor": "Transcription Factors", "descriptor_ui": "D014157", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019 Feb 7", "date_precision": "day", "issue": "4", "normalized_date": "2019-02-07", "pages": "882-896.e18", "proceedings_title": null, "publisher": "", "title": "Cell", "volume": "176", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "Genome-wide CRISPR Screens in T Helper Cells Reveal Pervasive Crosstalk between Activation and Differentiation.", "url": "https://riken-share.ent.box.com/folder/380762627000", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The transcription factor NF-kappaB performs various cell functions, such as regulating proliferation and differentiation and blocking apoptosis, by inducing the expression of multiple genes. The shuttling of NF-kappaB between the cytoplasm and nucleus is involved in its transcriptional activity in the canonical NF-kappaB pathway. The transcription of the NF-kappaB target genes is regulated by the phosphorylation of both IkappaBalpha and the RelA subunit of NF-kappaB, suggesting that these phosphorylation events are crucial for the oscillation. In this study, we constructed a new mathematical model of NF-kappaB activation to explore the modulation of the oscillation by the phosphorylation of IkappaBalpha and RelA. Based on a stability analysis around the equilibrium point, we confirmed that IkappaBalpha phosphorylation added a structure with a stable periodic solution to the phosphorylation model. The stable periodic solution appeared to transiently respond to the attenuation of the concentration of active IKKbeta. Because the NF-kappaB oscillation is caused by the periodic solution, the amplitude and period of the NF-kappaB oscillation in the phosphorylation model was constant regardless of the initial conditions; we defined this property as the reproducibility of the oscillation. On the other hand, the amplitude and period of the NF-kappaB oscillation depended on a parameter related to the RelA phosphorylation, suggesting that the oscillation period is regulated by RelA phosphorylation. In addition, the region of the periodic solution that is dependent on active IKKbeta also depends on a parameter related to RelA phosphorylation. Therefore, we conclude that the phosphorylation of both IkappaBalpha and RelA regulates the robustness of the NF-kappaB signaling module oscillation. That is, by appropriately controlling the phosphorylation process, it becomes possible to control the NF-kappaB oscillation and appropriately induce the NFkB-dependent expression gene. We anticipate that this study will contribute to the future elucidation of the mechanism underlying the nuclear cytoplasmic (N-C) oscillation of NF-kappaB.", "classifications": [ { "id": "Suzuki", "label": "Group Suzuki", "parent": "Takekawa", "type": "group" }, { "id": "Takekawa", "label": "Team Takekawa", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Naoya", "last_name": "Hatanaka", "name": null }, { "creator_type": "author", "first_name": "Takao", "last_name": "Seki", "name": null }, { "creator_type": "author", "first_name": "Jun-Ichiro", "last_name": "Inoue", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Tero", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Suzuki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.jtbi.2018.11.023" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "30496749" } }, "mesh": [ { "descriptor": "Biological Transport", "descriptor_ui": "D001692", "major_topic": false }, { "descriptor": "Cell Nucleus", "descriptor_ui": "D002467", "major_topic": false }, { "descriptor": "Cytoplasm", "descriptor_ui": "D003593", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Models, Biological", "descriptor_ui": "D008954", "major_topic": false }, { "descriptor": "NF-kappa B", "descriptor_ui": "D016328", "major_topic": false }, { "descriptor": "NF-KappaB Inhibitor alpha", "descriptor_ui": "D000072000", "major_topic": false }, { "descriptor": "Periodicity", "descriptor_ui": "D010507", "major_topic": true }, { "descriptor": "Phosphorylation", "descriptor_ui": "D010766", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": true }, { "descriptor": "Transcription Factor RelA", "descriptor_ui": "D051996", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019 Feb 7", "date_precision": "day", "issue": "", "normalized_date": "2019-02-07", "pages": "479-489", "proceedings_title": null, "publisher": "", "title": "Journal of theoretical biology", "volume": "462", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "Critical roles of IkappaBalpha and RelA phosphorylation in transitional oscillation in NF-kappaB signaling module.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "A new method for the synthesis of benzhydryl amines from the reaction of readily available sulfone derivatives with amines is described. The Cu-catalyzed desulfonylative amination not only provides structurally diverse benzhydryl amines in good yields, but is also applicable to iterative and intramolecular aminations. Control experiments suggested that the formation of a Cu-carbene intermediate generated from the sulfone substrate, which represents a new route for desulfonylative transformations.", "classifications": [ { "id": "Nanbo", "label": "Group Nanbo", "parent": "Tsuchiya", "type": "group" }, { "id": "Tsuchiya", "label": "Team Tsuchiya", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Masakazu", "last_name": "Nambo", "name": null }, { "creator_type": "author", "first_name": "Yasuyo", "last_name": "Tahara", "name": null }, { "creator_type": "author", "first_name": "Jacky C.-H.", "last_name": "Yim", "name": null }, { "creator_type": "author", "first_name": "Cathleen M.", "last_name": "Crudden", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/chem.201805638" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "30450672" } }, "mesh": [], "publication": { "conference_name": null, "date": "2019 Feb 6", "date_precision": "day", "issue": "8", "normalized_date": "2019-02-06", "pages": "1923-1926", "proceedings_title": null, "publisher": "", "title": "Chemistry (Weinheim an der Bergstrasse, Germany)", "volume": "25", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "Cu-Catalyzed Desulfonylative Amination of Benzhydryl Sulfones.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: CRISPR-Cas9 genome editing is widely used to study gene function, from basic biology to biomedical research. Structural rearrangements are a ubiquitous feature of cancer cells and their impact on the functional consequences of CRISPR-Cas9 gene-editing has not yet been assessed. RESULTS: Utilizing CRISPR-Cas9 knockout screens for 250 cancer cell lines, we demonstrate that targeting structurally rearranged regions, in particular tandem or interspersed amplifications, is highly detrimental to cellular fitness in a gene-independent manner. In contrast, amplifications caused by whole chromosomal duplication have little to no impact on fitness. This effect is cell line specific and dependent on the ploidy status. We devise a copy-number ratio metric that substantially improves the detection of gene-independent cell fitness effects in CRISPR-Cas9 screens. Furthermore, we develop a computational tool, called Crispy, to account for these effects on a single sample basis and provide corrected gene fitness effects. CONCLUSION: Our analysis demonstrates the importance of structural rearrangements in mediating the effect of CRISPR-Cas9-induced DNA damage, with implications for the use of CRISPR-Cas9 gene-editing in cancer cells.", "classifications": [ { "id": "Yusa", "label": "Group Yusa", "parent": "Eiraku", "type": "group" }, { "id": "Eiraku", "label": "Team Eiraku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Emanuel", "last_name": "Goncalves", "name": null }, { "creator_type": "author", "first_name": "Fiona M.", "last_name": "Behan", "name": null }, { "creator_type": "author", "first_name": "Sandra", "last_name": "Louzada", "name": null }, { "creator_type": "author", "first_name": "Damien", "last_name": "Arnol", "name": null }, { "creator_type": "author", "first_name": "Euan A.", "last_name": "Stronach", "name": null }, { "creator_type": "author", "first_name": "Fengtang", "last_name": "Yang", "name": null }, { "creator_type": "author", "first_name": "Kosuke", "last_name": "Yusa", "name": null }, { "creator_type": "author", "first_name": "Oliver", "last_name": "Stegle", "name": null }, { "creator_type": "author", "first_name": "Francesco", "last_name": "Iorio", "name": null }, { "creator_type": "author", "first_name": "Mathew J.", "last_name": "Garnett", "name": null } ], "identifiers": { "doi": { "normalized": "10.1186/s13059-019-1637-z" }, "pmcid": { "normalized": "PMC6362594" }, "pmid": { "normalized": "30722791" } }, "mesh": [ { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "CRISPR-Cas Systems", "descriptor_ui": "D064113", "major_topic": true }, { "descriptor": "Genomic Structural Variation", "descriptor_ui": "D056914", "major_topic": true }, { "descriptor": "Genomics", "descriptor_ui": "D023281", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Neoplasms", "descriptor_ui": "D009369", "major_topic": false }, { "descriptor": "Ploidies", "descriptor_ui": "D011003", "major_topic": false }, { "descriptor": "Software", "descriptor_ui": "D012984", "major_topic": false }, { "descriptor": "Whole Genome Sequencing", "descriptor_ui": "D000073336", "major_topic": true } ], "publication": { "conference_name": null, "date": "2019 Feb 5", "date_precision": "day", "issue": "1", "normalized_date": "2019-02-05", "pages": "27", "proceedings_title": null, "publisher": "", "title": "Genome biology", "volume": "20", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "Structural rearrangements generate cell-specific, gene-independent CRISPR-Cas9 loss of fitness effects.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "In most flowering plants, the asymmetric cell division of the zygote is the initial step in establishing the apical-basal axis of the mature plant. The zygote is polarized, possessing the nucleus at the apical tip and large vacuoles at the basal end. Despite their known polar localization, whether the positioning of the vacuoles and the nucleus is coordinated and what the role of the vacuole is in the asymmetric zygotic division remain elusive. In the present study, we utilized a live-cell imaging system to visualize the dynamics of vacuoles during the entire process of zygote polarization in Arabidopsis Image analysis revealed that the vacuoles formed tubular strands around the apically migrating nucleus. They gradually accumulated at the basal region and filled the space, resulting in asymmetric distribution in the mature zygote. To assess the role of vacuoles in the zygote, we screened various vacuole mutants and identified that shoot gravitropism2 (sgr2), in which the vacuolar structural change was impaired, failed to form tubular vacuoles and to polarly distribute the vacuole. In sgr2, large vacuoles occupied the apical tip and thus nuclear migration was blocked, resulting in a more symmetric zygotic division. We further observed that tubular vacuole formation and asymmetric vacuolar distribution both depended on the longitudinal array of actin filaments. Overall, our results show that vacuolar dynamics is crucial not only for the polar distribution along actin filaments but also for adequate nuclear positioning, and consequently zygote-division asymmetry.", "classifications": [ { "id": "Higaki", "label": "Group Higaki", "parent": "Ueda", "type": "group" }, { "id": "Ueda", "label": "Team Ueda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yusuke", "last_name": "Kimata", "name": null }, { "creator_type": "author", "first_name": "Takehide", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Takumi", "last_name": "Higaki", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Kurihara", "name": null }, { "creator_type": "author", "first_name": "Tomomi", "last_name": "Yamada", "name": null }, { "creator_type": "author", "first_name": "Shoji", "last_name": "Segami", "name": null }, { "creator_type": "author", "first_name": "Miyo Terao", "last_name": "Morita", "name": null }, { "creator_type": "author", "first_name": "Masayoshi", "last_name": "Maeshima", "name": null }, { "creator_type": "author", "first_name": "Seiichiro", "last_name": "Hasezawa", "name": null }, { "creator_type": "author", "first_name": "Tetsuya", "last_name": "Higashiyama", "name": null }, { "creator_type": "author", "first_name": "Masao", "last_name": "Tasaka", "name": null }, { "creator_type": "author", "first_name": "Minako", "last_name": "Ueda", "name": null } ], "identifiers": { "doi": { "normalized": "10.1073/pnas.1814160116" }, "pmcid": { "normalized": "PMC6369786" }, "pmid": { "normalized": "30651313" } }, "mesh": [ { "descriptor": "Actin Cytoskeleton", "descriptor_ui": "D008841", "major_topic": false }, { "descriptor": "Arabidopsis", "descriptor_ui": "D017360", "major_topic": false }, { "descriptor": "Arabidopsis Proteins", "descriptor_ui": "D029681", "major_topic": false }, { "descriptor": "Asymmetric Cell Division", "descriptor_ui": "D060049", "major_topic": true }, { "descriptor": "Cell Nucleus", "descriptor_ui": "D002467", "major_topic": false }, { "descriptor": "Cell Polarity", "descriptor_ui": "D016764", "major_topic": true }, { "descriptor": "Chloroplast Proteins", "descriptor_ui": "D060365", "major_topic": false }, { "descriptor": "Fluorescent Antibody Technique", "descriptor_ui": "D005455", "major_topic": false }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": false }, { "descriptor": "Vacuoles", "descriptor_ui": "D014617", "major_topic": false }, { "descriptor": "Zygote", "descriptor_ui": "D015053", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019 Feb 5", "date_precision": "day", "issue": "6", "normalized_date": "2019-02-05", "pages": "2338-2343", "proceedings_title": null, "publisher": "", "title": "Proceedings of the National Academy of Sciences of the United States of America", "volume": "116", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "Polar vacuolar distribution is essential for accurate asymmetric division of Arabidopsis zygotes.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Epigenetic information (epigenome) on chromatin is crucial for the determination of cellular identity and for the expression of cell type-specific biological functions. The cell type-specific epigenome is maintained beyond replication and cell division. Nucleosomes of chromatin just after DNA replication are a mixture of old histones with the parental epigenome and newly synthesized histones without such information. The diluted epigenome is mostly restored within one cell cycle using the epigenome on the parental DNA and nucleosomes as replication templates. However, many important questions about the epigenome replication process remain to be clarified. In this study, we investigated the model system comprising of dimethylated histone H3 lysine 9 (H3K9me2) and its regulation by the lysine methyltransferase G9a. Using this epigenome model system, we addressed whether H3K9me2 can be induced in specific cell cycle stages, especially G1. Using cell cycle-specific degrons, we achieved G1 or late G1-to M phases specific accumulation of exogenous G9a in G9a deficient cells. Importantly, global levels of H3K9me2 were significantly recovered by both cell types. These data indicate that H3K9me2 may be plastic and inducible, even in the long-living, terminally-differentiated, post-mitotic, G0-G1 cell population in vivo. This knowledge is valuable in designing epigenome-manipulation-based treatments for diseases.", "classifications": [ { "id": "Sawano", "label": "Group Sawano", "parent": "Shintaku", "type": "group" }, { "id": "Shintaku", "label": "Team Shintaku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Mikiko", "last_name": "Fukuda", "name": null }, { "creator_type": "author", "first_name": "Asako", "last_name": "Sakaue-Sawano", "name": null }, { "creator_type": "author", "first_name": "Chikako", "last_name": "Shimura", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Tachibana", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Miyawaki", "name": null }, { "creator_type": "author", "first_name": "Yoichi", "last_name": "Shinkai", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41598-018-37507-5" }, "pmcid": { "normalized": "PMC6354049" }, "pmid": { "normalized": "30700744" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "G1 Phase", "descriptor_ui": "D016193", "major_topic": true }, { "descriptor": "Geminin", "descriptor_ui": "D064248", "major_topic": false }, { "descriptor": "Histone-Lysine N-Methyltransferase", "descriptor_ui": "D011495", "major_topic": false }, { "descriptor": "Histones", "descriptor_ui": "D006657", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Lysine", "descriptor_ui": "D008239", "major_topic": false }, { "descriptor": "Methylation", "descriptor_ui": "D008745", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Mitosis", "descriptor_ui": "D008938", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019 Jan 30", "date_precision": "day", "issue": "1", "normalized_date": "2019-01-30", "pages": "956", "proceedings_title": null, "publisher": "", "title": "Scientific reports", "volume": "9", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "G9a-dependent histone methylation can be induced in G1 phase of cell cycle.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Imidazole-containing dipeptides (IDPs), such as carnosine and anserine, are found exclusively in various animal tissues, especially in the skeletal muscles and nerves. IDPs have antioxidant activity because of their metal-chelating and free radical-scavenging properties. However, the underlying mechanisms that would fully explain IDP antioxidant effects remain obscure. Here, using HPLC–electrospray ionization–tandem MS analyses, we comprehensively investigated carnosine and its related small peptides in the soluble fractions of mouse tissue homogenates and ubiquitously detected 2-oxo-histidine–containing dipeptides (2-oxo-IDPs) in all examined tissues. We noted enhanced production of the 2-oxo-IDPs in the brain of a mouse model of sepsis-associated encephalopathy. Moreover, in SH-SY5Y human neuroblastoma cells stably expressing carnosine synthase, H2O2 exposure resulted in the intracellular production of 2-oxo-carnosine, which was associated with significant inhibition of the H2O2 cytotoxicity. Notably, 2-oxo-carnosine showed a better antioxidant activity than endogenous antioxidants such as GSH and ascorbate. Mechanistic studies indicated that carnosine monooxygenation is mediated through the formation of a histidyl-imidazole radical, followed by the addition of molecular oxygen. Our findings reveal that 2-oxo-IDPs are metal-catalyzed oxidation products present in vivo and provide a revised paradigm for understanding the antioxidant effects of the IDPs.", "classifications": [ { "id": "Nishida", "label": "Group Nishida", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Hideshi", "last_name": "Ihara", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Kakihana", "name": null }, { "creator_type": "author", "first_name": "Akane", "last_name": "Yamakage", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Kai", "name": null }, { "creator_type": "author", "first_name": "Takahiro", "last_name": "Shibata", "name": null }, { "creator_type": "author", "first_name": "Motohiro", "last_name": "Nishida", "name": null }, { "creator_type": "author", "first_name": "Ken-ichi", "last_name": "Yamada", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Uchida", "name": null } ], "identifiers": { "doi": { "normalized": "10.1074/jbc.ra118.006111" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "30504220" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Antioxidants", "descriptor_ui": "D000975", "major_topic": false }, { "descriptor": "Carnosine", "descriptor_ui": "D002336", "major_topic": false }, { "descriptor": "Cell Survival", "descriptor_ui": "D002470", "major_topic": false }, { "descriptor": "Dipeptides", "descriptor_ui": "D004151", "major_topic": false }, { "descriptor": "Histidine", "descriptor_ui": "D006639", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Hydrogen Peroxide", "descriptor_ui": "D006861", "major_topic": false }, { "descriptor": "Imidazoles", "descriptor_ui": "D007093", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Muscle, Skeletal", "descriptor_ui": "D018482", "major_topic": false }, { "descriptor": "Neuroblastoma", "descriptor_ui": "D009447", "major_topic": false }, { "descriptor": "Oxidants", "descriptor_ui": "D016877", "major_topic": false }, { "descriptor": "Oxidation-Reduction", "descriptor_ui": "D010084", "major_topic": false }, { "descriptor": "Tumor Cells, Cultured", "descriptor_ui": "D014407", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019 Jan 25", "date_precision": "day", "issue": "4", "normalized_date": "2019-01-25", "pages": "1279-1289", "proceedings_title": null, "publisher": "", "title": "The Journal of Biological Chemistry", "volume": "294", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "2-Oxo-histidine–containing dipeptides are functional oxidation products.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Metabolome analysis using capillary electrophoresis (CE) coupled with high-resolution mass spectrometry (HRMS) has the potential to improve coverage of metabolite detection because of its high selectivity and sensitivity. Configuration of the interface between CE and HRMS to meet the ground connection is essential for enabling independent regulation of the electrical currents in the CE and electrospray field. In the present study, we applied an electrospray-ionization adapter equipped with a grounded nebulizer to CE-HRMS and tested the analytical performance for 34 charged compounds. The extracted-ion electropherograms, consisting of seven sets of isomers, showed reasonable peak shapes and separation for the annotation of each metabolite. The levels of 34 target analytes in a standard mixture were determined with a dynamic range of at least 10(2), maintaining linearity with r(2) > 0.9. The repeatability and intermediate precision above the lower limit of quantification showed the relative standard deviation to be lower than 20%. In the spike-recovery experiment, 27 of the 34 metabolites in plasma extract were recovered at a rate of 80 to 120%, suggesting high accuracy. Furthermore, we assessed the feasibility of our platform in metabolome analysis using human-plasma extract. The results showed successful detection of 270 metabolites, indicating the potential of our platform to yield higher coverage of the metabolome. In addition, analysis of dilution integrity demonstrated the quantitative ability of metabolome analysis with CE-HRMS, although the existence of saturation or matrix effects were seen in the case of 33 of the metabolites. This study indicates that our platform has great potential for large-scale metabolome analysis of plasma for biological studies and clinical biomarker screening.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Kazunori", "last_name": "Sasaki", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Sagawa", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Masaru", "last_name": "Tomita", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Yoshiaki", "last_name": "Ohashi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/acs.analchem.8b02994" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "30500154" } }, "mesh": [ { "descriptor": "Biomarkers", "descriptor_ui": "D015415", "major_topic": false }, { "descriptor": "Blood Chemical Analysis", "descriptor_ui": "D001774", "major_topic": false }, { "descriptor": "Electrophoresis, Capillary", "descriptor_ui": "D019075", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Metabolome", "descriptor_ui": "D055442", "major_topic": true }, { "descriptor": "Metabolomics", "descriptor_ui": "D055432", "major_topic": false }, { "descriptor": "Plasma", "descriptor_ui": "D010949", "major_topic": false }, { "descriptor": "Spectrometry, Mass, Electrospray Ionization", "descriptor_ui": "D021241", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019 Jan 15", "date_precision": "day", "issue": "2", "normalized_date": "2019-01-15", "pages": "1295-1301", "proceedings_title": null, "publisher": "", "title": "Analytical chemistry", "volume": "91", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "Metabolomics Platform with Capillary Electrophoresis Coupled with High-Resolution Mass Spectrometry for Plasma Analysis.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Chemical vapor deposition (CVD) utilizing metal cluster nanoparticle catalysts is commonly used to synthesize carbon nanotubes (CNT), with oxygen-containing species such as water or alcohol included in the feedstock for enhanced yield. However, the etching effect of these additives on the growth mechanism has rarely been investigated, despite evidence suggesting that etching potentially affects the chirality distribution of product CNTs. We used quantum chemical methods to study how water-based etchant radicals (OH and H) may enhance the chiral selectivity during CVD growth using CNT cap models. Chemical reactivities of the caps with the etchant radicals were evaluated using density functional theory (DFT). It was found that the reactivities on the cap edges correlate with the chirality of the caps. These results suggest that proper selection of etchant species can provide opportunities for selective chirality control of the product CNTs. (c) 2018 Wiley Periodicals, Inc.", "classifications": [ { "id": "Hijikata", "label": "Group Hijikata", "parent": "Tsuchiya", "type": "group" }, { "id": "Tsuchiya", "label": "Team Tsuchiya", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Ryuto", "last_name": "Kimura", "name": null }, { "creator_type": "author", "first_name": "Yuh", "last_name": "Hijikata", "name": null }, { "creator_type": "author", "first_name": "Clothilde A.", "last_name": "Eveleens", "name": null }, { "creator_type": "author", "first_name": "Alister J.", "last_name": "Page", "name": null }, { "creator_type": "author", "first_name": "Stephan", "last_name": "Irle", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/jcc.25610" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "30548651" } }, "mesh": [], "publication": { "conference_name": null, "date": "2019 Jan 15", "date_precision": "day", "issue": "2", "normalized_date": "2019-01-15", "pages": "375-380", "proceedings_title": null, "publisher": "", "title": "Journal of computational chemistry", "volume": "40", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "Chiral-selective etching effects on carbon nanotube growth at edge carbon atoms.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Apelin is an inotropic and cardioprotective peptide that exhibits beneficial effects through activation of the APJ receptor in the pathology of cardiovascular diseases. Apelin induces the expression of angiotensin-converting enzyme 2 (ACE2) in failing hearts, thereby improving heart function in an angiotensin 1⁻7-dependent manner. Whether apelin antagonizes the over-activation of the renin⁻angiotensin system in the heart remains elusive. In this study we show that the detrimental effects of angiotensin II (Ang II) were exacerbated in the hearts of aged apelin-gene-deficient mice. Ang II-mediated cardiac dysfunction and hypertrophy were augmented in apelin knockout mice. The loss of apelin increased the ratio of angiotensin-converting enzyme (ACE) to ACE2 expression in the Ang II-stressed hearts, and Ang II-induced cardiac fibrosis was markedly enhanced in apelin knockout mice. mRNA expression of pro-fibrotic genes, such as transforming growth-factor beta (TGF-β) signaling, were significantly upregulated in apelin knockout hearts. Consistently, treatment with the ACE-inhibitor Captopril decreased cardiac contractility in apelin knockout mice. In vitro, apelin ameliorated Ang II-induced TGF-β expression in primary cardiomyocytes, accompanied with reduced hypertrophy. These results provide direct evidence that endogenous apelin plays a crucial role in suppressing Ang II-induced cardiac dysfunction and pathological remodeling.", "classifications": [ { "id": "Suzuki", "label": "Group Suzuki", "parent": "Takekawa", "type": "group" }, { "id": "Takekawa", "label": "Team Takekawa", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Teruki", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Ayumi", "last_name": "Kadowaki", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Yumiko", "last_name": "Imai", "name": null }, { "creator_type": "author", "first_name": "Keiji", "last_name": "Kuba", "name": null } ], "identifiers": { "doi": { "normalized": "10.3390/ijms20020239" }, "pmcid": { "normalized": "PMC6358887" }, "pmid": { "normalized": "30634441" } }, "mesh": [ { "descriptor": "Angiotensin II", "descriptor_ui": "D000804", "major_topic": false }, { "descriptor": "Angiotensin-Converting Enzyme 2", "descriptor_ui": "D000085962", "major_topic": false }, { "descriptor": "Angiotensin-Converting Enzyme Inhibitors", "descriptor_ui": "D000806", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Apelin", "descriptor_ui": "D000073861", "major_topic": false }, { "descriptor": "Biopsy", "descriptor_ui": "D001706", "major_topic": false }, { "descriptor": "Cardiomegaly", "descriptor_ui": "D006332", "major_topic": false }, { "descriptor": "Disease Models, Animal", "descriptor_ui": "D004195", "major_topic": false }, { "descriptor": "Echocardiography", "descriptor_ui": "D004452", "major_topic": false }, { "descriptor": "Fibrosis", "descriptor_ui": "D005355", "major_topic": false }, { "descriptor": "Heart Failure", "descriptor_ui": "D006333", "major_topic": false }, { "descriptor": "Hypertension", "descriptor_ui": "D006973", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Myocardial Contraction", "descriptor_ui": "D009200", "major_topic": false }, { "descriptor": "Myocytes, Cardiac", "descriptor_ui": "D032383", "major_topic": false }, { "descriptor": "Peptidyl-Dipeptidase A", "descriptor_ui": "D007703", "major_topic": false }, { "descriptor": "Ventricular Dysfunction", "descriptor_ui": "D018754", "major_topic": false }, { "descriptor": "Ventricular Remodeling", "descriptor_ui": "D020257", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019 Jan 9", "date_precision": "day", "issue": "2", "normalized_date": "2019-01-09", "pages": "", "proceedings_title": null, "publisher": "", "title": "International journal of molecular sciences", "volume": "20", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "Loss of Apelin Augments Angiotensin II-Induced Cardiac Dysfunction and Pathological Remodeling.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Mutations in the ATM tumor suppressor gene confer hypersensitivity to DNA-damaging chemotherapeutic agents. To explore genetic resistance mechanisms, we performed genome-wide CRISPR-Cas9 screens in cells treated with the DNA topoisomerase I inhibitor topotecan. Thus, we here establish that inactivating terminal components of the non-homologous end-joining (NHEJ) machinery or of the BRCA1-A complex specifically confer topotecan resistance to ATM-deficient cells. We show that hypersensitivity of ATM-mutant cells to topotecan or the poly-(ADP-ribose) polymerase (PARP) inhibitor olaparib reflects delayed engagement of homologous recombination at DNA-replication-fork associated single-ended double-strand breaks (DSBs), allowing some to be subject to toxic NHEJ. Preventing DSB ligation by NHEJ, or enhancing homologous recombination by BRCA1-A complex disruption, suppresses this toxicity, highlighting a crucial role for ATM in preventing toxic LIG4-mediated chromosome fusions. Notably, suppressor mutations in ATM-mutant backgrounds are different to those in BRCA1-mutant scenarios, suggesting new opportunities for patient stratification and additional therapeutic vulnerabilities for clinical exploitation.", "classifications": [ { "id": "Yusa", "label": "Group Yusa", "parent": "Eiraku", "type": "group" }, { "id": "Eiraku", "label": "Team Eiraku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Gabriel", "last_name": "Balmus", "name": null }, { "creator_type": "author", "first_name": "Domenic", "last_name": "Pilger", "name": null }, { "creator_type": "author", "first_name": "Julia", "last_name": "Coates", "name": null }, { "creator_type": "author", "first_name": "Mukerrem", "last_name": "Demir", "name": null }, { "creator_type": "author", "first_name": "Matylda", "last_name": "Sczaniecka-Clift", "name": null }, { "creator_type": "author", "first_name": "Ana C.", "last_name": "Barros", "name": null }, { "creator_type": "author", "first_name": "Michael", "last_name": "Woods", "name": null }, { "creator_type": "author", "first_name": "Beiyuan", "last_name": "Fu", "name": null }, { "creator_type": "author", "first_name": "Fengtang", "last_name": "Yang", "name": null }, { "creator_type": "author", "first_name": "Elisabeth", "last_name": "Chen", "name": null }, { "creator_type": "author", "first_name": "Matthias", "last_name": "Ostermaier", "name": null }, { "creator_type": "author", "first_name": "Tatjana", "last_name": "Stankovic", "name": null }, { "creator_type": "author", "first_name": "Hannes", "last_name": "Ponstingl", "name": null }, { "creator_type": "author", "first_name": "Mareike", "last_name": "Herzog", "name": null }, { "creator_type": "author", "first_name": "Kosuke", "last_name": "Yusa", "name": null }, { "creator_type": "author", "first_name": "Francisco Munoz", "last_name": "Martinez", "name": null }, { "creator_type": "author", "first_name": "Stephen T.", "last_name": "Durant", "name": null }, { "creator_type": "author", "first_name": "Yaron", "last_name": "Galanty", "name": null }, { "creator_type": "author", "first_name": "Petra", "last_name": "Beli", "name": null }, { "creator_type": "author", "first_name": "David J.", "last_name": "Adams", "name": null }, { "creator_type": "author", "first_name": "Allan", "last_name": "Bradley", "name": null }, { "creator_type": "author", "first_name": "Emmanouil", "last_name": "Metzakopian", "name": null }, { "creator_type": "author", "first_name": "Josep V.", "last_name": "Forment", "name": null }, { "creator_type": "author", "first_name": "Stephen P.", "last_name": "Jackson", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41467-018-07729-2" }, "pmcid": { "normalized": "PMC6325118" }, "pmid": { "normalized": "30622252" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Antineoplastic Agents", "descriptor_ui": "D000970", "major_topic": false }, { "descriptor": "Ataxia Telangiectasia Mutated Proteins", "descriptor_ui": "D064007", "major_topic": false }, { "descriptor": "BRCA1 Protein", "descriptor_ui": "D019313", "major_topic": false }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Cell Survival", "descriptor_ui": "D002470", "major_topic": false }, { "descriptor": "CRISPR-Cas Systems", "descriptor_ui": "D064113", "major_topic": false }, { "descriptor": "DNA Breaks, Double-Stranded", "descriptor_ui": "D053903", "major_topic": false }, { "descriptor": "DNA End-Joining Repair", "descriptor_ui": "D059766", "major_topic": false }, { "descriptor": "DNA Ligase ATP", "descriptor_ui": "D000072481", "major_topic": false }, { "descriptor": "DNA Replication", "descriptor_ui": "D004261", "major_topic": false }, { "descriptor": "Drug Resistance, Neoplasm", "descriptor_ui": "D019008", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred NOD", "descriptor_ui": "D016688", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Mouse Embryonic Stem Cells", "descriptor_ui": "D000066450", "major_topic": false }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": false }, { "descriptor": "Neoplasms, Experimental", "descriptor_ui": "D009374", "major_topic": false }, { "descriptor": "Phthalazines", "descriptor_ui": "D010793", "major_topic": false }, { "descriptor": "Piperazines", "descriptor_ui": "D010879", "major_topic": false }, { "descriptor": "Topotecan", "descriptor_ui": "D019772", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019 Jan 8", "date_precision": "day", "issue": "1", "normalized_date": "2019-01-08", "pages": "87", "proceedings_title": null, "publisher": "", "title": "Nature communications", "volume": "10", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "ATM orchestrates the DNA-damage response to counter toxic non-homologous end-joining at broken replication forks.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Tumors are composed of both cancer stem-like cells (CSCs) and differentiated cancer cells. Each CSC can undergo either a symmetric cell division to produce two CSCs or an asymmetric cell division to produce one CSC and one differentiated cancer cell. It is believed that the rate of symmetric division increases as more CSCs become malignant; however, underlying molecular mechanisms remain elusive. Here we show that stimulation with a cytokine, semaphorin (Sema), activates monooxygenase of MICAL3, a cytoplasmic signal transducer, through the neuropilin (NP) receptor that is specifically expressed on the breast CSC plasma membrane. The activation of MICAL3 induces symmetric division of CSCs. Each molecule in this signaling pathway represents a promising therapeutic target for eliminating CSCs.", "classifications": [ { "id": "Okamoto", "label": "Group Okamoto", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Kana", "last_name": "Tominaga", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Minato", "name": null }, { "creator_type": "author", "first_name": "Takahiko", "last_name": "Murayama", "name": null }, { "creator_type": "author", "first_name": "Asako", "last_name": "Sasahara", "name": null }, { "creator_type": "author", "first_name": "Tatsunori", "last_name": "Nishimura", "name": null }, { "creator_type": "author", "first_name": "Etsuko", "last_name": "Kiyokawa", "name": null }, { "creator_type": "author", "first_name": "Hajime", "last_name": "Kanauchi", "name": null }, { "creator_type": "author", "first_name": "Seiichiro", "last_name": "Shimizu", "name": null }, { "creator_type": "author", "first_name": "Ayaka", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Kotoe", "last_name": "Nishioka", "name": null }, { "creator_type": "author", "first_name": "Ei-ichi", "last_name": "Tsuji", "name": null }, { "creator_type": "author", "first_name": "Masao", "last_name": "Yano", "name": null }, { "creator_type": "author", "first_name": "Toshihisa", "last_name": "Ogawa", "name": null }, { "creator_type": "author", "first_name": "Hideshi", "last_name": "Ishii", "name": null }, { "creator_type": "author", "first_name": "Masaki", "last_name": "Mori", "name": null }, { "creator_type": "author", "first_name": "Koichi", "last_name": "Akashi", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Okamoto", "name": null }, { "creator_type": "author", "first_name": "Masahiko", "last_name": "Tanabe", "name": null }, { "creator_type": "author", "first_name": "Kei-ichiro", "last_name": "Tada", "name": null }, { "creator_type": "author", "first_name": "Arinobu", "last_name": "Tojo", "name": null }, { "creator_type": "author", "first_name": "Noriko", "last_name": "Gotoh", "name": null } ], "identifiers": { "doi": { "normalized": "10.1073/pnas.1806851116" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "30587593" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Breast Neoplasms", "descriptor_ui": "D001943", "major_topic": false }, { "descriptor": "Cell Division", "descriptor_ui": "D002455", "major_topic": true }, { "descriptor": "Gene Knockdown Techniques", "descriptor_ui": "D055785", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mixed Function Oxygenases", "descriptor_ui": "D006899", "major_topic": false }, { "descriptor": "Neoplasm Proteins", "descriptor_ui": "D009363", "major_topic": false }, { "descriptor": "Neoplastic Stem Cells", "descriptor_ui": "D014411", "major_topic": false }, { "descriptor": "Semaphorin-3A", "descriptor_ui": "D040121", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": true }, { "descriptor": "Spheroids, Cellular", "descriptor_ui": "D018874", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019 Jan 8", "date_precision": "day", "issue": "2", "normalized_date": "2019-01-08", "pages": "625-630", "proceedings_title": null, "publisher": "", "title": "Proceedings of the National Academy of Sciences of the United States of America", "volume": "116", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "Semaphorin signaling via MICAL3 induces symmetric cell division to expand breast cancer stem-like cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Seed exudates influence the behavior of soil organisms, but how this occurs remains unclear, particularly for multicellular animals. Here we show that compounds associated with Arabidopsis seed-coat mucilage regulate the behavior of soil-borne animals, specifically root-knot nematodes (RKNs). Infective RKN J2 larvae actively travel toward Arabidopsis seeds through chemotaxis. Analysis of Arabidopsis mucilage mutants demonstrated that the attraction of RKNs to Arabidopsis seeds requires the synthesis and extrusion of seed-coat mucilage. Extracted mucilage alone is not sufficient to attract RKNs, but seed-surface carbohydrates and proteins are required for this process. These findings suggest that the RKN chemoattractant is synthesized de novo upon mucilage extrusion but may be highly unstable. RKNs attracted by this mucilage-dependent mechanism can infect the emerging seedling. However, the attraction signal from seedling roots likely acts independently of the seed-coat signal and may mask the attraction to seed-coat mucilage after germination. Multiple RKN species are attracted by Arabidopsis seeds, suggesting that this mechanism is conserved in RKNs. These findings indicate that seed exudate can regulate the behavior of multicellular animals and highlight the potential roles of seed-coat mucilage in biotic interactions with soil microorganisms.", "classifications": [ { "id": "Higaki", "label": "Group Higaki", "parent": "Ueda", "type": "group" }, { "id": "Ueda", "label": "Team Ueda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Allen Yi-Lun", "last_name": "Tsai", "name": null }, { "creator_type": "author", "first_name": "Takumi", "last_name": "Higaki", "name": null }, { "creator_type": "author", "first_name": "Chinh-Nghia", "last_name": "Nguyen", "name": null }, { "creator_type": "author", "first_name": "Laetitia", "last_name": "Perfus-Barbeoch", "name": null }, { "creator_type": "author", "first_name": "Bruno", "last_name": "Favery", "name": null }, { "creator_type": "author", "first_name": "Shinichiro", "last_name": "Sawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.molp.2018.11.008" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "30503864" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Arabidopsis", "descriptor_ui": "D017360", "major_topic": false }, { "descriptor": "Behavior, Animal", "descriptor_ui": "D001522", "major_topic": false }, { "descriptor": "Chemotaxis", "descriptor_ui": "D002633", "major_topic": false }, { "descriptor": "Nematoda", "descriptor_ui": "D009348", "major_topic": false }, { "descriptor": "Plant Exudates", "descriptor_ui": "D053147", "major_topic": false }, { "descriptor": "Plant Mucilage", "descriptor_ui": "D062087", "major_topic": false }, { "descriptor": "Seeds", "descriptor_ui": "D012639", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019 Jan 7", "date_precision": "day", "issue": "1", "normalized_date": "2019-01-07", "pages": "99-112", "proceedings_title": null, "publisher": "", "title": "Molecular plant", "volume": "12", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "Regulation of Root-Knot Nematode Behavior by Seed-Coat Mucilage-Derived Attractants.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "In plants, the position of lateral roots (LRs) depends on initiation sites induced by auxin. The domain of high auxin response responsible for LR initiation stretches over several cells, but only a pair of pericycle cells (LR founder cells) will develop into LRs. In this work, we identified a signaling cascade controlling LR formation through lateral inhibition. It comprises a peptide hormone TARGET OF LBD SIXTEEN 2 (TOLS2), its receptor RLK7, and a downstream transcription factor PUCHI. TOLS2 is expressed at the LR founder cells and inhibits LR initiation. Time-lapse imaging of auxin-responsive DR5:LUCIFERASE reporter expression revealed that occasionally two pairs of LR founder cells are specified in close proximity even in wild-type and that one of them exists only transiently and disappears in an RLK7-dependent manner. We propose that the selection of LR founder cells by the peptide hormone-receptor cascade ensures proper LR spacing.", "classifications": [ { "id": "Fujimoto", "label": "Group Fujimoto", "parent": "Ueda", "type": "group" }, { "id": "Ueda", "label": "Team Ueda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Koichi", "last_name": "Toyokura", "name": null }, { "creator_type": "author", "first_name": "Tatsuaki", "last_name": "Goh", "name": null }, { "creator_type": "author", "first_name": "Hidefumi", "last_name": "Shinohara", "name": null }, { "creator_type": "author", "first_name": "Akinori", "last_name": "Shinoda", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Kondo", "name": null }, { "creator_type": "author", "first_name": "Yoshie", "last_name": "Okamoto", "name": null }, { "creator_type": "author", "first_name": "Takeo", "last_name": "Uehara", "name": null }, { "creator_type": "author", "first_name": "Koichi", "last_name": "Fujimoto", "name": null }, { "creator_type": "author", "first_name": "Yoko", "last_name": "Okushima", "name": null }, { "creator_type": "author", "first_name": "Yoshifumi", "last_name": "Ikeyama", "name": null }, { "creator_type": "author", "first_name": "Keiji", "last_name": "Nakajima", "name": null }, { "creator_type": "author", "first_name": "Tetsuro", "last_name": "Mimura", "name": null }, { "creator_type": "author", "first_name": "Masao", "last_name": "Tasaka", "name": null }, { "creator_type": "author", "first_name": "Yoshikatsu", "last_name": "Matsubayashi", "name": null }, { "creator_type": "author", "first_name": "Hidehiro", "last_name": "Fukaki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.devcel.2018.11.031" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "30581155" } }, "mesh": [ { "descriptor": "Arabidopsis", "descriptor_ui": "D017360", "major_topic": false }, { "descriptor": "Arabidopsis Proteins", "descriptor_ui": "D029681", "major_topic": false }, { "descriptor": "Cell Communication", "descriptor_ui": "D002450", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Cell Division", "descriptor_ui": "D002455", "major_topic": false }, { "descriptor": "Gene Expression Regulation, Plant", "descriptor_ui": "D018506", "major_topic": false }, { "descriptor": "Indoleacetic Acids", "descriptor_ui": "D007210", "major_topic": false }, { "descriptor": "Organogenesis, Plant", "descriptor_ui": "D063246", "major_topic": false }, { "descriptor": "Plant Roots", "descriptor_ui": "D018517", "major_topic": false }, { "descriptor": "Plants, Genetically Modified", "descriptor_ui": "D030821", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019 Jan 7", "date_precision": "day", "issue": "1", "normalized_date": "2019-01-07", "pages": "64-75.e5", "proceedings_title": null, "publisher": "", "title": "Developmental cell", "volume": "48", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "Lateral Inhibition by a Peptide Hormone-Receptor Cascade during Arabidopsis Lateral Root Founder Cell Formation.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "This research examined post-disaster consumer perception of food value and their effects on purchase intent by focusing on Japanese seafood industry after the Great East Japan earthquake. Online surveys on consumers living in Tokyo and Osaka Prefectures were conducted to investigate consumer value perceptions of Miyagi salmon in 2012 and 2015. Multiple-group structural equation modeling (SEM) on the 2012 survey results showed that desire to contribute to restoration (social value) had the greatest positive influence on purchase intent in both regions. Concern about radiation threats (safety value) had a negative influence on purchase intent, with a stronger impact in Osaka than Tokyo. In comparison, the 2015 results revealed a reduction in the effects of these two potent factors (i.e., safety value and social value) on purchase intent only in Osaka. The beneficial value of seafood had a general positive influence on purchase intent, but its magnitude of effect differed by regional and chronological context. Among these three values, sales promotion with emphasis on social value is more effective than with other values. In cases of future disasters in a similar context, marketers are recommended to adopt different value transfer strategies according to geographical and temporal diversity.", "classifications": [ { "id": "Suzuki", "label": "Group Suzuki", "parent": "Takekawa", "type": "group" }, { "id": "Takekawa", "label": "Team Takekawa", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Takashi", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Taro", "last_name": "Oishi", "name": null }, { "creator_type": "author", "first_name": "Hisashi", "last_name": "Kurokura", "name": null }, { "creator_type": "author", "first_name": "Nobuyuki", "last_name": "Yagi", "name": null } ], "identifiers": { "doi": { "normalized": "10.3390/foods8010014" }, "pmcid": { "normalized": "PMC6352202" }, "pmid": { "normalized": "30621184" } }, "mesh": [], "publication": { "conference_name": null, "date": "2019 Jan 4", "date_precision": "day", "issue": "1", "normalized_date": "2019-01-04", "pages": "", "proceedings_title": null, "publisher": "", "title": "Foods (Basel, Switzerland)", "volume": "8", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "Which Aspects of Food Value Promote Consumer Purchase Intent after a Disaster? A Case Study of Salmon Products in Disaster-Affected Areas of the Great East Japan Earthquake.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "A 66-year-old male undergoing maintenance hemodialysis presented with mild thrombocytopenia. He also had aortic valve stenosis and required aortic valve replacement. In addition, he required anticoagulation therapy with warfarin because of chronic subclavian artery occlusion. He was eventually diagnosed with immune thrombocytopenic purpura (ITP), although there were no bleeding tendencies. The patient was preoperatively treated with thrombopoietin receptor agonist (romiplostim((R))) because of the risk of bleeding complication during cardiac surgery. The platelet count rapidly increased with low-dose romiplostim, and no thrombotic complication occurred. During surgery, no significant bleeding complications were observed. This report suggests that romiplostim is a useful treatment option for the management of bleeding complication during cardiac surgery in a hemodialysis patient with ITP.", "classifications": [ { "id": "Nishikii", "label": "Group Nishikii", "parent": "Shintaku", "type": "group" }, { "id": "Shintaku", "label": "Team Shintaku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Hidekazu", "last_name": "Nishikii", "name": null }, { "creator_type": "author", "first_name": "Naoki", "last_name": "Kurita", "name": null }, { "creator_type": "author", "first_name": "Manabu", "last_name": "Kusakabe", "name": null }, { "creator_type": "author", "first_name": "Yasuhisa", "last_name": "Yokoyama", "name": null }, { "creator_type": "author", "first_name": "Takayasu", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Mamiko", "last_name": "Sakata-Yanagimoto", "name": null }, { "creator_type": "author", "first_name": "Naoshi", "last_name": "Obara", "name": null }, { "creator_type": "author", "first_name": "Yuichi", "last_name": "Hasegawa", "name": null }, { "creator_type": "author", "first_name": "Shigeru", "last_name": "Chiba", "name": null } ], "identifiers": { "doi": { "normalized": "10.11406/rinketsu.60.28" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "30726820" } }, "mesh": [ { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Cardiac Surgical Procedures", "descriptor_ui": "D006348", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Platelet Count", "descriptor_ui": "D010976", "major_topic": false }, { "descriptor": "Purpura, Thrombocytopenic, Idiopathic", "descriptor_ui": "D016553", "major_topic": false }, { "descriptor": "Receptors, Fc", "descriptor_ui": "D011961", "major_topic": false }, { "descriptor": "Receptors, Thrombopoietin", "descriptor_ui": "D053628", "major_topic": false }, { "descriptor": "Recombinant Fusion Proteins", "descriptor_ui": "D011993", "major_topic": false }, { "descriptor": "Renal Dialysis", "descriptor_ui": "D006435", "major_topic": false }, { "descriptor": "Thrombopoietin", "descriptor_ui": "D013926", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019", "date_precision": "year", "issue": "1", "normalized_date": "2019", "pages": "28-32", "proceedings_title": null, "publisher": "", "title": "[Rinsho ketsueki] The Japanese journal of clinical hematology", "volume": "60", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "[Successful management of primary immune thrombocytopenia with romiplostim during open heart surgery in a hemodialysis patient].", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "8-Nitroguanosine 3',5'-cyclic monophosphate (8-nitro-cGMP), which is the second messenger in nitric oxide/reactive oxygen species redox signaling, covalently binds to protein thiol groups (called S-guanylation) and exerts various biological functions. Synaptosomal associated protein 25 (SNAP-25), a member of soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins, plays an important role in the process of membrane fusion. We previously showed that SNAP-25 is S-guanylated at cysteine 90. In addition, we revealed that S-guanylation of SNAP-25 increases SNARE complex formation, but decreases the affinity of SNARE complex for complexin. Since SNAP-25 plays a critical role in regulating exocytosis, it is important to elucidate the physiological or pathophysiological meanings of S-guanylation of this protein. Here we describe a protocol for detecting 8-nitro-cGMP and S-guanylated proteins in cells by immunocytochemistry, and methods to detect SNARE complex in 8-nitro-cGMP-treated cells.", "classifications": [ { "id": "Akaike", "label": "Group Akaike", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yusuke", "last_name": "Kishimoto", "name": null }, { "creator_type": "author", "first_name": "Takaaki", "last_name": "Akaike", "name": null }, { "creator_type": "author", "first_name": "Hideshi", "last_name": "Ihara", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/978-1-4939-8760-3_9" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "30317503" } }, "mesh": [ { "descriptor": "Cell Culture Techniques", "descriptor_ui": "D018929", "major_topic": false }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Cyclic GMP", "descriptor_ui": "D006152", "major_topic": false }, { "descriptor": "Cysteine", "descriptor_ui": "D003545", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Immunohistochemistry", "descriptor_ui": "D007150", "major_topic": false }, { "descriptor": "Membrane Fusion", "descriptor_ui": "D008561", "major_topic": false }, { "descriptor": "Native Polyacrylamide Gel Electrophoresis", "descriptor_ui": "D063347", "major_topic": false }, { "descriptor": "Protein Structure, Quaternary", "descriptor_ui": "D020836", "major_topic": true }, { "descriptor": "Synaptosomal-Associated Protein 25", "descriptor_ui": "D050825", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019", "date_precision": "year", "issue": "", "normalized_date": "2019", "pages": "163-173", "proceedings_title": null, "publisher": "", "title": "Methods in molecular biology (Clifton, N.J.)", "volume": "1860", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "SNAP-25 S-Guanylation and SNARE Complex Formation.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Excessive increase in blood glucose level after eating increases the risk of macroangiopathy, and a method for not increasing the postprandial blood glucose level is desired. However, a logical design method of the dietary ingestion pattern controlling the postprandial blood glucose level has not yet been established. We constructed a mathematical model of blood glucose control by oral glucose ingestion in three healthy human subjects, and predicted that intermittent ingestion 30 min apart was the optimal glucose ingestion patterns that minimized the peak value of blood glucose level. We confirmed with subjects that this intermittent pattern consistently decreased the peak value of blood glucose level. We also predicted insulin minimization pattern, and found that the intermittent ingestion 30 min apart was optimal, which is similar to that of glucose minimization pattern. Taken together, these results suggest that the glucose minimization is achieved by suppressing the peak value of insulin concentration, rather than by enhancing insulin concentration. This approach could be applied to design optimal dietary ingestion patterns.", "classifications": [ { "id": "Kuroda", "label": "Group Kuroda", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Masashi", "last_name": "Fujii", "name": null }, { "creator_type": "author", "first_name": "Yohei", "last_name": "Murakami", "name": null }, { "creator_type": "author", "first_name": "Yasuaki", "last_name": "Karasawa", "name": null }, { "creator_type": "author", "first_name": "Yohei", "last_name": "Sumitomo", "name": null }, { "creator_type": "author", "first_name": "Suguru", "last_name": "Fujita", "name": null }, { "creator_type": "author", "first_name": "Masanori", "last_name": "Koyama", "name": null }, { "creator_type": "author", "first_name": "Shinsuke", "last_name": "Uda", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Kubota", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Inoue", "name": null }, { "creator_type": "author", "first_name": "Katsumi", "last_name": "Konishi", "name": null }, { "creator_type": "author", "first_name": "Shigeyuki", "last_name": "Oba", "name": null }, { "creator_type": "author", "first_name": "Shin", "last_name": "Ishii", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Kuroda", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41540-019-0108-1" }, "pmcid": { "normalized": "PMC6718521" }, "pmid": { "normalized": "31508240" } }, "mesh": [ { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Blood Glucose", "descriptor_ui": "D001786", "major_topic": false }, { "descriptor": "C-Peptide", "descriptor_ui": "D002096", "major_topic": false }, { "descriptor": "Diet", "descriptor_ui": "D004032", "major_topic": false }, { "descriptor": "Eating", "descriptor_ui": "D004435", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Glucose", "descriptor_ui": "D005947", "major_topic": false }, { "descriptor": "Healthy Volunteers", "descriptor_ui": "D064368", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Insulin", "descriptor_ui": "D007328", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Models, Theoretical", "descriptor_ui": "D008962", "major_topic": false }, { "descriptor": "Postprandial Period", "descriptor_ui": "D019518", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019", "date_precision": "year", "issue": "", "normalized_date": "2019", "pages": "31", "proceedings_title": null, "publisher": "", "title": "NPJ systems biology and applications", "volume": "5", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "Logical design of oral glucose ingestion pattern minimizing blood glucose in humans.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "A 38-year-old woman with aggressive clinical course of chronic lymphocytic leukemia (CLL) was treated with 8 courses of R-CHOP. Clinical remission was achieved, while B-cell clonality remained. Allogeneic hematopoietic stem cell transplantation was performed with reduced intensity conditioning (fludarabine and 2-Gy total body irradiation). However, autologous hematopoietic recovery occurred within a month after the transplant. Nevertheless, B-cell clonality became undetectable at 14 days after transplant, which has been kept so for over 10 years with clinical remission. Cytogenetic analyses were repeatedly performed and demonstrated nonclonal chromosomal aberrations, although the patient did not develop any secondary malignancies. One possible explanation for the clinical course is a very short-term allogeneic immune reaction helping eradication of residual CLL cells.", "classifications": [ { "id": "Nishikii", "label": "Group Nishikii", "parent": "Shintaku", "type": "group" }, { "id": "Shintaku", "label": "Team Shintaku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Hidekazu", "last_name": "Nishikii", "name": null }, { "creator_type": "author", "first_name": "Naoki", "last_name": "Kurita", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Shinagawa", "name": null }, { "creator_type": "author", "first_name": "Tatsuhiro", "last_name": "Sakamoto", "name": null }, { "creator_type": "author", "first_name": "Manabu", "last_name": "Kusakabe", "name": null }, { "creator_type": "author", "first_name": "Yasuhisa", "last_name": "Yokoyama", "name": null }, { "creator_type": "author", "first_name": "Takayasu", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Mamiko", "last_name": "Sakata-Yanagimoto", "name": null }, { "creator_type": "author", "first_name": "Naoshi", "last_name": "Obara", "name": null }, { "creator_type": "author", "first_name": "Yuichi", "last_name": "Hasegawa", "name": null }, { "creator_type": "author", "first_name": "Naoya", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Shigeru", "last_name": "Chiba", "name": null } ], "identifiers": { "doi": { "normalized": "10.1155/2019/9710790" }, "pmcid": { "normalized": "PMC6335663" }, "pmid": { "normalized": "30719361" } }, "mesh": [], "publication": { "conference_name": null, "date": "2019", "date_precision": "year", "issue": "", "normalized_date": "2019", "pages": "9710790", "proceedings_title": null, "publisher": "", "title": "Case reports in hematology", "volume": "2019", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "Durable Leukemic Remission and Autologous Marrow Recovery with Random Chromosomal Abnormalities after Allogeneic Hematopoietic Stem Cell Transplantation for Chronic Lymphocytic Leukemia.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "This review describes the features of molecular biology techniques for single-cell RNA sequencing (scRNA-seq), including methods developed in our laboratory. Existing scRNA-seq methods require the conversion of first-strand cDNA to amplifiable cDNA followed by whole-transcript amplification. There are three primary strategies for this conversion: poly-A tagging, template switching, and RNase H-DNA polymerase I-mediated second-strand cDNA synthesis for in vitro transcription. We discuss the merits and limitations of these strategies and describe our Reverse Transcription with Random Displacement Amplification technology that allows for direct first-strand cDNA amplification from RNA without the need for conversion to an amplifiable cDNA. We believe that this review provides all users of single-cell transcriptome technologies with an understanding of the relationship between the quantitative performance of various methods and their molecular features.", "classifications": [ { "id": "Nikaido", "label": "Group Nikaido", "parent": "Fujiwara", "type": "group" }, { "id": "Fujiwara", "label": "Team Fujiwara", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yohei", "last_name": "Sasagawa", "name": null }, { "creator_type": "author", "first_name": "Tetsutaro", "last_name": "Hayashi", "name": null }, { "creator_type": "author", "first_name": "Itoshi", "last_name": "Nikaido", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/978-981-13-6037-4_1" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "30968357" } }, "mesh": [ { "descriptor": "DNA, Complementary", "descriptor_ui": "D018076", "major_topic": false }, { "descriptor": "RNA", "descriptor_ui": "D012313", "major_topic": false }, { "descriptor": "Sequence Analysis, RNA", "descriptor_ui": "D017423", "major_topic": false }, { "descriptor": "Single-Cell Analysis", "descriptor_ui": "D059010", "major_topic": false }, { "descriptor": "Transcriptome", "descriptor_ui": "D059467", "major_topic": true } ], "publication": { "conference_name": null, "date": "2019", "date_precision": "year", "issue": "", "normalized_date": "2019", "pages": "1-17", "proceedings_title": null, "publisher": "", "title": "Advances in experimental medicine and biology", "volume": "1129", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "Strategies for Converting RNA to Amplifiable cDNA for Single-Cell RNA Sequencing Methods.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Thymic crosstalk, a set of reciprocal regulations between thymocytes and the thymic environment, is relevant for orchestrating appropriate thymocyte development as well as thymic recovery from various exogenous insults. In this work, interactions shaping thymic crosstalk and the resultant dynamics of thymocytes and thymic epithelial cells are inferred based on quantitative analysis and modeling of the recovery dynamics induced by irradiation. The analysis identifies regulatory interactions consistent with known molecular evidence and reveals their dynamic roles in the recovery process. Moreover, the analysis also predicts, and a subsequent experiment verifies, a previously unrecognized regulation of CD4+CD8+ double positive thymocytes which temporarily increases their proliferation rate upon the decrease in their population size. Our model establishes a pivotal step towards the dynamic understanding of thymic crosstalk as a regulatory network system.", "classifications": [ { "id": "Kobayashi", "label": "Group Kobayashi", "parent": "Wakamoto", "type": "group" }, { "id": "Wakamoto", "label": "Team Wakamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Kazumasa B.", "last_name": "Kaneko", "name": null }, { "creator_type": "author", "first_name": "Ryosuke", "last_name": "Tateishi", "name": null }, { "creator_type": "author", "first_name": "Takahisa", "last_name": "Miyao", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Takakura", "name": null }, { "creator_type": "author", "first_name": "Nobuko", "last_name": "Akiyama", "name": null }, { "creator_type": "author", "first_name": "Ryo", "last_name": "Yokota", "name": null }, { "creator_type": "author", "first_name": "Taishin", "last_name": "Akiyama", "name": null }, { "creator_type": "author", "first_name": "Tetsuya J.", "last_name": "Kobayashi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s42003-019-0688-8" }, "pmcid": { "normalized": "PMC6884561" }, "pmid": { "normalized": "31815199" } }, "mesh": [ { "descriptor": "Algorithms", "descriptor_ui": "D000465", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Communication", "descriptor_ui": "D002450", "major_topic": true }, { "descriptor": "Cell Proliferation", "descriptor_ui": "D049109", "major_topic": false }, { "descriptor": "Cellular Microenvironment", "descriptor_ui": "D060833", "major_topic": true }, { "descriptor": "Epithelial Cells", "descriptor_ui": "D004847", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Models, Biological", "descriptor_ui": "D008954", "major_topic": true }, { "descriptor": "Radiation, Ionizing", "descriptor_ui": "D011839", "major_topic": false }, { "descriptor": "Recovery of Function", "descriptor_ui": "D020127", "major_topic": false }, { "descriptor": "Thymocytes", "descriptor_ui": "D060168", "major_topic": false }, { "descriptor": "Thymus Gland", "descriptor_ui": "D013950", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019", "date_precision": "year", "issue": "", "normalized_date": "2019", "pages": "444", "proceedings_title": null, "publisher": "", "title": "Communications biology", "volume": "2", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "Quantitative analysis reveals reciprocal regulations underlying recovery dynamics of thymocytes and thymic environment in mice.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "An understanding of the intracellular distribution of bioactive small molecules provides insight into their target organelles and biomolecules, and throws light on their molecular mechanisms of action and specificity. Many studies in this area have employed fluorescence imaging, using molecules of interest labeled with fluorescent dyes. However, modification with a bulky fluorophore may significantly alter the properties, including bioactivity, of small molecules. To address this issue, we have recently developed Raman scattering microscopy of alkyne tags to visualize small molecules in biological systems. The tiny alkyne tag should have a minimal effect on the properties of the tagged molecule, and the unique alkyne vibrational properties allow observation of the Raman signals of the tagged molecules in a wavelength region where there is little interference from Raman signals of endogenous biomolecules. Here we summarize the methodology for Raman imaging of alkyne-tagged bioactive small molecules in living biological systems including the development of slit-scanning Raman microscope, which is useful for fast imaging of alkyne-tagged molecules.", "classifications": [ { "id": "Fujita", "label": "Group Fujita", "parent": "Fujita", "type": "group" }, { "id": "Sodeoka", "label": "Group Sodeoka", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Jun", "last_name": "Ando", "name": null }, { "creator_type": "author", "first_name": "Kosuke", "last_name": "Dodo", "name": null }, { "creator_type": "author", "first_name": "Katsumasa", "last_name": "Fujita", "name": null }, { "creator_type": "author", "first_name": "Mikiko", "last_name": "Sodeoka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/978-1-4939-8891-4_5" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "30519942" } }, "mesh": [ { "descriptor": "Alkynes", "descriptor_ui": "D000480", "major_topic": true }, { "descriptor": "Biological Assay", "descriptor_ui": "D001681", "major_topic": true }, { "descriptor": "Cell Culture Techniques", "descriptor_ui": "D018929", "major_topic": false }, { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "Drug Discovery", "descriptor_ui": "D055808", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Image Processing, Computer-Assisted", "descriptor_ui": "D007091", "major_topic": false }, { "descriptor": "Small Molecule Libraries", "descriptor_ui": "D054852", "major_topic": false }, { "descriptor": "Spectrum Analysis, Raman", "descriptor_ui": "D013059", "major_topic": true } ], "publication": { "conference_name": null, "date": "2019", "date_precision": "year", "issue": "", "normalized_date": "2019", "pages": "99-114", "proceedings_title": null, "publisher": "", "title": "Methods in molecular biology (Clifton, N.J.)", "volume": "1888", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "Visualizing Bioactive Small Molecules by Alkyne Tagging and Slit-Scanning Raman Microscopy.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Pulmonary arterial hypertension (PAH) is characterized by remodeling and narrowing of the pulmonary arteries, which lead to elevation of right ventricular pressure, heart failure, and death. Proliferation of pulmonary artery smooth muscle cells (PASMCs) is thought to be central to the pathogenesis of PAH, although the underlying mechanisms are still being explored. The protein p53 is involved in cell cycle coordination, DNA repair, apoptosis, and cellular senescence, but its role in pulmonary hypertension (PH) is not fully known. We developed a mouse model of hypoxia-induced pulmonary hypertension (PH) and found significant reduction of p53 expression in the lungs. Our in vitro experiments with metabolomic analyses and the Seahorse XF extracellular flux analyzer indicated that suppression of p53 expression in PASMCs led to upregulation of glycolysis and downregulation of mitochondrial respiration, suggesting a proliferative phenotype resembling that of cancer cells. It was previously shown that systemic genetic depletion of p53 in a murine PH model led to more severe lung manifestations. Lack of information about the role of cell-specific p53 signaling promoted us to investigate it in our mouse PH model with the inducible Cre-loxP system. We generated a mouse model with SMC-specific gain or loss of p53 function by crossing Myh11-Cre/ERT2 mice with floxed Mdm4 mice or floxed Trp53 mice. After these animals were exposed to hypoxia for 4 weeks, we conducted hemodynamic and echocardiographic studies. Surprisingly, the severity of PH was similar in both groups of mice and there were no differences between the genotypes. Our findings in these mice indicate that activation or suppression of p53 signaling in SMCs has a minor role in the pathogenesis of PH and suggest that p53 signaling in other cells (endothelial cells, immune cells, or fibroblasts) may be involved in the progression of this condition.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Takayuki", "last_name": "Wakasugi", "name": null }, { "creator_type": "author", "first_name": "Ippei", "last_name": "Shimizu", "name": null }, { "creator_type": "author", "first_name": "Yohko", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Yuka", "last_name": "Hayashi", "name": null }, { "creator_type": "author", "first_name": "Ryutaro", "last_name": "Ikegami", "name": null }, { "creator_type": "author", "first_name": "Masayoshi", "last_name": "Suda", "name": null }, { "creator_type": "author", "first_name": "Goro", "last_name": "Katsuumi", "name": null }, { "creator_type": "author", "first_name": "Masaaki", "last_name": "Nakao", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Hoyano", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Kashimura", "name": null }, { "creator_type": "author", "first_name": "Kazufumi", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Nojiri", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Tohru", "last_name": "Minamino", "name": null } ], "identifiers": { "doi": { "normalized": "10.1371/journal.pone.0212889" }, "pmcid": { "normalized": "PMC6391010" }, "pmid": { "normalized": "30807606" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Apoptosis", "descriptor_ui": "D017209", "major_topic": false }, { "descriptor": "Blotting, Western", "descriptor_ui": "D015153", "major_topic": false }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Cellular Senescence", "descriptor_ui": "D016922", "major_topic": false }, { "descriptor": "DNA Repair", "descriptor_ui": "D004260", "major_topic": false }, { "descriptor": "Echocardiography", "descriptor_ui": "D004452", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Hypertension, Pulmonary", "descriptor_ui": "D006976", "major_topic": false }, { "descriptor": "Hypoxia", "descriptor_ui": "D000860", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Metabolomics", "descriptor_ui": "D055432", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Myocytes, Smooth Muscle", "descriptor_ui": "D032389", "major_topic": false }, { "descriptor": "RNA, Small Interfering", "descriptor_ui": "D034741", "major_topic": false }, { "descriptor": "Tumor Suppressor Protein p53", "descriptor_ui": "D016159", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019", "date_precision": "year", "issue": "2", "normalized_date": "2019", "pages": "e0212889", "proceedings_title": null, "publisher": "", "title": "PloS one", "volume": "14", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "Role of smooth muscle cell p53 in pulmonary arterial hypertension.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Proper regulation of epigenetic states of chromatin is crucial to achieve tissue-specific gene expression during embryogenesis. The lung-specific gene products, surfactant proteins B (SP-B) and C (SP-C), are synthesized in alveolar epithelial cells and prevent alveolar collapse. Epigenetic regulation of these surfactant proteins, however, remains unknown. Here we report that MCRIP1, a regulator of the CtBP transcriptional co-repressor, promotes the expression of SP-B and SP-C by preventing CtBP-mediated epigenetic gene silencing. Homozygous deficiency of Mcrip1 in mice causes fatal respiratory distress due to abnormal transcriptional repression of these surfactant proteins. We found that MCRIP1 interferes with interactions of CtBP with the lung-enriched transcriptional repressors, Foxp1 and Foxp2, thereby preventing the recruitment of the CtBP co-repressor complex to the SP-B and SP-C promoters and maintaining them in an active chromatin state. Our findings reveal a molecular mechanism by which cells prevent inadvertent gene silencing to ensure tissue-specific gene expression during organogenesis.", "classifications": [ { "id": "Takekawa", "label": "Group Takekawa", "parent": "Takekawa", "type": "group" }, { "id": "Takekawa", "label": "Team Takekawa", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Jane S.", "last_name": "Weng", "name": null }, { "creator_type": "author", "first_name": "Takanori", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Hisashi", "last_name": "Moriizumi", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Takano", "name": null }, { "creator_type": "author", "first_name": "Ryoji", "last_name": "Yao", "name": null }, { "creator_type": "author", "first_name": "Mutsuhiro", "last_name": "Takekawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s42003-019-0478-3" }, "pmcid": { "normalized": "PMC6586819" }, "pmid": { "normalized": "31240265" } }, "mesh": [ { "descriptor": "Alcohol Oxidoreductases", "descriptor_ui": "D000429", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Co-Repressor Proteins", "descriptor_ui": "D056970", "major_topic": false }, { "descriptor": "DNA-Binding Proteins", "descriptor_ui": "D004268", "major_topic": false }, { "descriptor": "Epithelium", "descriptor_ui": "D004848", "major_topic": false }, { "descriptor": "Forkhead Transcription Factors", "descriptor_ui": "D051858", "major_topic": false }, { "descriptor": "Gene Expression", "descriptor_ui": "D015870", "major_topic": false }, { "descriptor": "Gene Silencing", "descriptor_ui": "D020868", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Intracellular Signaling Peptides and Proteins", "descriptor_ui": "D047908", "major_topic": false }, { "descriptor": "Lung", "descriptor_ui": "D008168", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Pulmonary Surfactant-Associated Protein B", "descriptor_ui": "D037701", "major_topic": false }, { "descriptor": "Pulmonary Surfactant-Associated Protein C", "descriptor_ui": "D037721", "major_topic": false }, { "descriptor": "Repressor Proteins", "descriptor_ui": "D012097", "major_topic": false }, { "descriptor": "Respiratory Insufficiency", "descriptor_ui": "D012131", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019", "date_precision": "year", "issue": "", "normalized_date": "2019", "pages": "227", "proceedings_title": null, "publisher": "", "title": "Communications biology", "volume": "2", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "MCRIP1 promotes the expression of lung-surfactant proteins in mice by disrupting CtBP-mediated epigenetic gene silencing.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "INTRODUCTION: The natural history of consolidation on computed tomography (CT) rarely includes invasive cancers, and evidence of the ideal timing for surgical intervention via long-term follow-up studies remains unknown. METHODS: Between January 2012 and June 2017, pulmonary resection was undertaken in 293 clinical IA patients who were followed-up for > 6 months after the first detection of potential non-small-cell lung cancer (NSCLC) opacities. We evaluated the corresponding HRs and compared the recurrence risk with the CT follow-up duration. RESULTS: HRs calculated for the longest intervals were compared between two patient subsets: a shorter-interval surgery group (SISG: 41.3%; mean follow-up interval, 13.5±5.3 months) and a longer-interval surgery group (58.7%; mean follow-up interval, 54.9±25.6 months). On Cox multivariate regression analyses, CT consolidation (ratio >0.5), an abnormal carcinoembryonic antigen and a triple-negative mutation showed an independent association with an unfavorable prognosis, as measured by disease-free survival after the first detection of potential NSCLC opacities. The longer-interval surgery group fared significantly better than the SISG in terms of 5-year overall survival after the first detection (99.3% vs 93.1%, P<0.01); the 3-year overall survival after the first detection was significantly shorter in the high-risk SISG (presence of two factors from the three) than that in the low-risk SISG (presence of 0 or one factor; 100% vs 73.3%, P<0.01). CONCLUSION: Our study indicates that the patients with potential NSCLC opacities who are able to wait for more than 2 years prior to pulmonary resection may be likely to have a favorable prognosis, whereas early judgment for surgical resection should be required for avoiding surgical delays.", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Hiroaki", "last_name": "Kuroda", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Sugita", "name": null }, { "creator_type": "author", "first_name": "Yuko", "last_name": "Ohya", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Takaaki", "last_name": "Arimura", "name": null }, { "creator_type": "author", "first_name": "Noriaki", "last_name": "Sakakura", "name": null }, { "creator_type": "author", "first_name": "Toyoaki", "last_name": "Hida", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null }, { "creator_type": "author", "first_name": "Yukinori", "last_name": "Sakao", "name": null } ], "identifiers": { "doi": { "normalized": "10.2147/cmar.s180757" }, "pmcid": { "normalized": "PMC6305139" }, "pmid": { "normalized": "30588114" } }, "mesh": [], "publication": { "conference_name": null, "date": "2019", "date_precision": "year", "issue": "", "normalized_date": "2019", "pages": "107-115", "proceedings_title": null, "publisher": "", "title": "Cancer management and research", "volume": "11", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "Importance of avoiding surgery delays after initial discovery of suspected non-small-cell lung cancer in clinical stage IA patients.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Japanese martial arts, Budo, have been reported to improve cognitive function, especially attention. However, the underlying neural mechanisms of the effect of Budo on attention processing has not yet been investigated. Kendo, a type of fencing using bamboo swords, is one of the most popular forms of Budo worldwide. We investigated the difference in functional connectivity (FC) between Kendo players (KPs) and non-KPs (NKPs) during an attention-related auditory oddball paradigm and during rest. The analyses focused on the brain network related to \"motivation.\" Resting-state functional magnetic resonance imaging (rs-fMRI) and task-based fMRI using the oddball paradigm were performed in healthy male volunteers (14 KPs and 11 NKPs). Group differences in FC were tested using CONN-software within the motivation network, which consisted of 22 brain regions defined by a previous response-conflict task-based fMRI study with a reward cue. Daily general physical activities were assessed using the International Physical Activity Questionnaire (IPAQ). We also investigated the impact of major confounders, namely, smoking habits, alcohol consumption, IPAQ score, body mass index (BMI), and reaction time (RT) in the oddball paradigm. Resting-state fMRI revealed that KPs had a significantly lower FC than NKPs between the right nucleus accumbens and right frontal eye field (FEF) within the motivation network. Conversely, KPs exhibited a significantly higher FC than NKPs between the left intraparietal sulcus (IPS) and the left precentral gyrus (PCG) within the network during the auditory oddball paradigm [statistical thresholds, False Discovery Rate (FDR) < 0.05]. These results remained significant after controlling for major covariates. Our results suggest that attenuated motivation network integrity at rest together with enhanced motivation network integrity during attentional demands might underlie the instantaneous concentration abilities of KPs.", "classifications": [ { "id": "Fujiwara", "label": "Group Fujiwara", "parent": "Fujiwara", "type": "group" }, { "id": "Fujiwara", "label": "Team Fujiwara", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Hironobu", "last_name": "Fujiwara", "name": null }, { "creator_type": "author", "first_name": "Tsukasa", "last_name": "Ueno", "name": null }, { "creator_type": "author", "first_name": "Sayaka", "last_name": "Yoshimura", "name": null }, { "creator_type": "author", "first_name": "Kei", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Miyagi", "name": null }, { "creator_type": "author", "first_name": "Naoya", "last_name": "Oishi", "name": null }, { "creator_type": "author", "first_name": "Toshiya", "last_name": "Murai", "name": null } ], "identifiers": { "doi": { "normalized": "10.3389/fnhum.2019.00170" }, "pmcid": { "normalized": "PMC6539200" }, "pmid": { "normalized": "31191277" } }, "mesh": [], "publication": { "conference_name": null, "date": "2019", "date_precision": "year", "issue": "", "normalized_date": "2019", "pages": "170", "proceedings_title": null, "publisher": "", "title": "Frontiers in human neuroscience", "volume": "13", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "Martial Arts \"Kendo\" and the Motivation Network During Attention Processing: An fMRI Study.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Under iron (Fe) deficiency, graminaceous plants produce and secrete Fe-chelating phytosiderophores of the mugineic acid (MA) family into the rhizosphere to solubilize and mediate uptake of sparingly soluble Fe in the soil. MAs and their biosynthetic intermediate, nicotianamine (NA), are also important for the translocation of divalent metals such as Fe and zinc (Zn) throughout the plant body. In this study, the physiological role of the efflux transporter EFFLUX TRANSPORTER OF NA (ENA1), which exports NA out of cells, was analyzed in rice. Promoter-GUS analysis showed that ENA1 was mainly expressed in roots, and strongly upregulated under Fe-deficient conditions. In epidermal onion cells and rice roots, green fluorescent protein-tagged ENA1 localized mainly to the plasma membrane, while a part of the fluorescence was observed in vesicular structures in the cytoplasm. In the younger stage after germination, ENA1-overexpressing rice plants exhibited truncated roots with many root hairs compared to wild-type plants, while these phenotype were not observed in high Zn-containing medium. In Arabidopsis, which use a different strategy for Fe uptake from rice, ENA1 overexpression did not show any apparent phenotypes. Oligo DNA microarray analysis in rice showed that ENA1 knockout affects the response to stress, especially in root plastids. These results suggest that ENA1 might be recycling between the plasma membrane and cellular compartments by vesicular transport, playing an important role in the transport of NA, which is important for the physiological response to Fe deficiency.", "classifications": [ { "id": "Sato", "label": "Group Sato", "parent": "Tsuchiya", "type": "group" }, { "id": "Tsuchiya", "label": "Team Tsuchiya", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Tomoko", "last_name": "Nozoye", "name": null }, { "creator_type": "author", "first_name": "Nicolaus", "last_name": "von Wiren", "name": null }, { "creator_type": "author", "first_name": "Yoshikatsu", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Tetsuya", "last_name": "Higashiyama", "name": null }, { "creator_type": "author", "first_name": "Hiromi", "last_name": "Nakanishi", "name": null }, { "creator_type": "author", "first_name": "Naoko K.", "last_name": "Nishizawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.3389/fpls.2019.00502" }, "pmcid": { "normalized": "PMC6503003" }, "pmid": { "normalized": "31114596" } }, "mesh": [], "publication": { "conference_name": null, "date": "2019", "date_precision": "year", "issue": "", "normalized_date": "2019", "pages": "502", "proceedings_title": null, "publisher": "", "title": "Frontiers in plant science", "volume": "10", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "Characterization of the Nicotianamine Exporter ENA1 in Rice.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "", "classifications": [ { "id": "Enomoto", "label": "Group Enomoto", "parent": "Enomoto", "type": "group" }, { "id": "Enomoto", "label": "Team Enomoto", "type": "team" } ], "creators": [ { "creator_type": "editor", "first_name": "Quenten", "last_name": "Schwarz", "name": null }, { "creator_type": "editor", "first_name": "Sophie", "last_name": "Wiszniak", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/978-1-4939-9412-0" }, "pmcid": { "normalized": null }, "pmid": { "normalized": null } }, "mesh": [], "publication": { "conference_name": null, "date": "2019", "date_precision": "year", "issue": null, "normalized_date": "2019", "pages": null, "proceedings_title": null, "publisher": "Springer New York", "title": null, "volume": "1976", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "Neural Crest Cells: Methods and Protocols", "url": "http://link.springer.com/10.1007/978-1-4939-9412-0", "zotero": { "item_type": "book" } }, { "abstract": "The sarcomere, the minimal mechanical unit of muscle, is composed of myosins, which self-assemble into thick filaments that interact with actin-based thin filaments in a highly-structured lattice. This complex imposes a geometric restriction on myosin in force generation. However, how single myosins generate force within the restriction remains elusive and conventional synthetic filaments do not recapitulate the symmetric bipolar filaments in sarcomeres. Here we engineered thick filaments using DNA origami that incorporate human muscle myosin to directly visualize the motion of the heads during force generation in a restricted space. We found that when the head diffuses, it weakly interacts with actin filaments and then strongly binds preferentially to the forward region as a Brownian ratchet. Upon strong binding, the two-step lever-arm swing dominantly halts at the first step and occasionally reverses direction. Our results illustrate the usefulness of our DNA origami-based assay system to dissect the mechanistic details of motor proteins.", "classifications": [ { "id": "Iwaki", "label": "Group Iwaki", "parent": "Toyoshima", "type": "group" }, { "id": "Toyoshima", "label": "Team Toyoshima", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Keisuke", "last_name": "Fujita", "name": null }, { "creator_type": "author", "first_name": "Masashi", "last_name": "Ohmachi", "name": null }, { "creator_type": "author", "first_name": "Keigo", "last_name": "Ikezaki", "name": null }, { "creator_type": "author", "first_name": "Toshio", "last_name": "Yanagida", "name": null }, { "creator_type": "author", "first_name": "Mitsuhiro", "last_name": "Iwaki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s42003-019-0683-0" }, "pmcid": { "normalized": "PMC6881340" }, "pmid": { "normalized": "31799438" } }, "mesh": [ { "descriptor": "Cytoskeletal Proteins", "descriptor_ui": "D003598", "major_topic": false }, { "descriptor": "Cytoskeleton", "descriptor_ui": "D003599", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Microscopy, Atomic Force", "descriptor_ui": "D018625", "major_topic": false }, { "descriptor": "Models, Biological", "descriptor_ui": "D008954", "major_topic": false }, { "descriptor": "Muscle Contraction", "descriptor_ui": "D009119", "major_topic": true }, { "descriptor": "Myosin Type II", "descriptor_ui": "D024462", "major_topic": false }, { "descriptor": "Protein Binding", "descriptor_ui": "D011485", "major_topic": false }, { "descriptor": "Single Molecule Imaging", "descriptor_ui": "D000072760", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019", "date_precision": "year", "issue": "", "normalized_date": "2019", "pages": "437", "proceedings_title": null, "publisher": "", "title": "Communications biology", "volume": "2", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "Direct visualization of human myosin II force generation using DNA origami-based thick filaments.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Recent outstanding progress in microscopic imaging technology and the advent of fluorescent probes have enabled us to visualize high spatiotemporal dynamics of intracellular molecules in living tissues. Here I introduce our research outcomes on functional fluorescence imaging of the heart especially for understanding the pathogenesis of cardiac arrhythmias. On the in situ Ca(2+) imaging of perfused rat heart by rapid-scanning confocal microscopy, we found that burst emergence of intracellular Ca(2+) waves evokes arrhythmogenic triggered activity and subsequent oscillatory depolarizations via the Na(+)-Ca(2+) exchanger. Besides, impairment of Ca(2+) release from the sarcoplasmic reticulum leads to emergence of Ca(2+) waves and spatiotemporally inhomogeneous Ca(2+) dynamics on systole, resulting in beat-to-beat Ca(2+) alternans. Such alternating behaviors of Ca(2+) dynamics are partly due to poor development of the transverse tubules, which are identified in murine atria and failing ventricular myocytes. In addition, impairment of the gap junctional communication via connexin 43 induced by dominant negative inhibition of neonatal rat ventricular myocyte monolayers results in generation of spiral wave reentry, suggesting the pivotal role of intercellular communications in genesis of arrhythmias. Furthermore, alterations in atrial histoanatomy, e.g., density and arrangements of myocytes and distribution of Cx43, could provide intrinsic arrhythmogenic bases of atrial fibrillation, which was revealed by combined optical imaging of the atria and precise histoanatomical examinations. In combination, fluorescence imaging of the living organisms provides indispensable information for unveiling functions and disease states.", "classifications": [ { "id": "Tanaka", "label": "Group Tanaka", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Hideo", "last_name": "Tanaka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1254/fpj.154.171" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "31597895" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Arrhythmias, Cardiac", "descriptor_ui": "D001145", "major_topic": false }, { "descriptor": "Calcium Signaling", "descriptor_ui": "D020013", "major_topic": true }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Heart", "descriptor_ui": "D006321", "major_topic": false }, { "descriptor": "Heart Atria", "descriptor_ui": "D006325", "major_topic": false }, { "descriptor": "Myocytes, Cardiac", "descriptor_ui": "D032383", "major_topic": false }, { "descriptor": "Optical Imaging", "descriptor_ui": "D061848", "major_topic": true }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Sodium-Calcium Exchanger", "descriptor_ui": "D019831", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019", "date_precision": "year", "issue": "4", "normalized_date": "2019", "pages": "171-177", "proceedings_title": null, "publisher": "", "title": "Nihon yakurigaku zasshi. Folia pharmacologica Japonica", "volume": "154", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "[Fluorescence imaging of the living heart for understanding the basis of arrhythmias].", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: BRAF (v-raf murine sarcoma viral oncogene homolog B1) V600E mutant colorectal cancer is associated with short survival. Recently, clinical trials have been conducted to improve outcomes of second or later lines of chemotherapy. However, there is a paucity of reference data pertaining to outcomes of second-line chemotherapy and prognostic factors that are relevant only to BRAF mutant patients. PATIENTS AND METHODS: We retrospectively reviewed metastatic colorectal cancer patients with BRAF V600E mutation who underwent second-line chemotherapy between January 2007 and March 2017. We evaluated treatment outcomes and performed prognostic analyses. RESULTS: A total of 52 patients were included. The median progression-free survival and overall survival (OS) were 2.5 [95% confidence interval (CI) = 1.91-4.11] and 6.5 (95% CI = 4.30-9.63) months, respectively. Overall response and disease control rates were 7% and 48%, respectively. All the regimens which elicited a partial response included BRAF inhibitors in combination with anti-epidermal growth factor receptor (EGFR) antibodies. Therefore, the overall response was 0% after exclusion of patients treated with study drugs. Multivariate analysis for OS revealed that the Glasgow Prognostic Score (GPS), elevated lactate dehydrogenase, and poor performance status were independent prognostic factors. In particular, survival curves according to the GPS stratified the patients into distinct risk groups. The median OSs in patients with GPS of 0, 1, and 2 were 9.9, 5.0, and 1.9 months, respectively. CONCLUSIONS: Outcomes of second-line chemotherapy for metastatic colorectal cancer patients with BRAF V600E mutation were extremely poor. GPS may be useful in future clinical trials.", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Seiichiro", "last_name": "Mitani", "name": null }, { "creator_type": "author", "first_name": "Hiroya", "last_name": "Taniguchi", "name": null }, { "creator_type": "author", "first_name": "Keiji", "last_name": "Sugiyama", "name": null }, { "creator_type": "author", "first_name": "Toshiki", "last_name": "Masuishi", "name": null }, { "creator_type": "author", "first_name": "Kazunori", "last_name": "Honda", "name": null }, { "creator_type": "author", "first_name": "Yukiya", "last_name": "Narita", "name": null }, { "creator_type": "author", "first_name": "Shigenori", "last_name": "Kadowaki", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Ura", "name": null }, { "creator_type": "author", "first_name": "Masashi", "last_name": "Ando", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Tajika", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null }, { "creator_type": "author", "first_name": "Kei", "last_name": "Muro", "name": null } ], "identifiers": { "doi": { "normalized": "10.1177/1758835918820298" }, "pmcid": { "normalized": "PMC6348546" }, "pmid": { "normalized": "30719102" } }, "mesh": [], "publication": { "conference_name": null, "date": "2019", "date_precision": "year", "issue": "", "normalized_date": "2019", "pages": "1758835918820298", "proceedings_title": null, "publisher": "", "title": "Therapeutic advances in medical oncology", "volume": "11", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "The impact of the Glasgow Prognostic Score on survival in second-line chemotherapy for metastatic colorectal cancer patients with BRAF V600E mutation.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Various branch architectures are observed in living organisms including plants. Branch formation has traditionally been an area of interest in the field of developmental biology, and theoretical approaches are now commonly used to understand the complex mechanisms involved. In this review article, we provide an overview of theoretical approaches including mathematical models and computer simulations for studying plant branch formation. These approaches cover a wide range of topics. In particular, we focus on the importance of positional information in branch formation, which has been especially revealed by theoretical research in plants including computations of developmental processes.", "classifications": [ { "id": "Higaki", "label": "Group Higaki", "parent": "Ueda", "type": "group" }, { "id": "Ueda", "label": "Team Ueda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Akiko", "last_name": "Nakamasu", "name": null }, { "creator_type": "author", "first_name": "Takumi", "last_name": "Higaki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/s10265-019-01107-9" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "31004242" } }, "mesh": [ { "descriptor": "Models, Theoretical", "descriptor_ui": "D008962", "major_topic": false }, { "descriptor": "Plant Development", "descriptor_ui": "D063245", "major_topic": true }, { "descriptor": "Plant Stems", "descriptor_ui": "D018547", "major_topic": false }, { "descriptor": "Plants", "descriptor_ui": "D010944", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019", "date_precision": "year", "issue": "3", "normalized_date": "2019", "pages": "325-333", "proceedings_title": null, "publisher": "", "title": "Journal of Plant Research", "volume": "132", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "Theoretical models for branch formation in plants.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Time-lapse imaging of gut explants from embryonic mice in which neural crest-derived cells express fluorescent proteins allows the behavior of enteric neural crest cells to be observed and analyzed. Explants of embryonic gut are dissected, mounted on filter paper supports so the gut retains its tubular three-dimensional structure, and then placed in coverglass bottom culture dishes in tissue culture medium. A stainless steel ring is placed on top of the filter support to prevent movement. Imaging is performed using a confocal microscope in an environmental chamber. A z series of images through the network of fluorescent cells is collected every 3, 5, or 10 min. At the end of imaging, the z series are projected.", "classifications": [ { "id": "Enomoto", "label": "Group Enomoto", "parent": "Enomoto", "type": "group" }, { "id": "Enomoto", "label": "Team Enomoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Marlene M.", "last_name": "Hao", "name": null }, { "creator_type": "author", "first_name": "Annette J.", "last_name": "Bergner", "name": null }, { "creator_type": "author", "first_name": "Donald F.", "last_name": "Newgreen", "name": null }, { "creator_type": "author", "first_name": "Hideki", "last_name": "Enomoto", "name": null }, { "creator_type": "author", "first_name": "Heather M.", "last_name": "Young", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/978-1-4939-9412-0_8" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "30977068" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Cell Movement", "descriptor_ui": "D002465", "major_topic": false }, { "descriptor": "Enteric Nervous System", "descriptor_ui": "D017615", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Neural Crest", "descriptor_ui": "D009432", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019", "date_precision": "year", "issue": "", "normalized_date": "2019", "pages": "97-105", "proceedings_title": null, "publisher": "", "title": "Methods in molecular biology (Clifton, N.J.)", "volume": "1976", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "Technologies for Live Imaging of Enteric Neural Crest-Derived Cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Plant leaves occur in diverse shapes. Divarication patterns that develop during early growths are one of key factors that determine leaf shapes. We utilized leaves of Microsorum pteropus, a semi-aquatic fern, and closely related varieties to analyze a variation in the divarication patterns. The leaves exhibited three major types of divarication: no lobes, bifurcation, and trifurcation (i.e., monopodial branching). Our investigation of their developmental processes, using time-lapse imaging, revealed localized growths and dissections of blades near each leaf apex. Restricted cell divisions responsible for the apical growths were confirmed using a pulse-chase strategy for EdU labeling assays.", "classifications": [ { "id": "Higaki", "label": "Group Higaki", "parent": "Ueda", "type": "group" }, { "id": "Ueda", "label": "Team Ueda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Saori", "last_name": "Miyoshi", "name": null }, { "creator_type": "author", "first_name": "Seisuke", "last_name": "Kimura", "name": null }, { "creator_type": "author", "first_name": "Ryo", "last_name": "Ootsuki", "name": null }, { "creator_type": "author", "first_name": "Takumi", "last_name": "Higaki", "name": null }, { "creator_type": "author", "first_name": "Akiko", "last_name": "Nakamasu", "name": null } ], "identifiers": { "doi": { "normalized": "10.1371/journal.pone.0210141" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "30682033" } }, "mesh": [ { "descriptor": "Cell Division", "descriptor_ui": "D002455", "major_topic": false }, { "descriptor": "Plant Epidermis", "descriptor_ui": "D019441", "major_topic": false }, { "descriptor": "Plant Leaves", "descriptor_ui": "D018515", "major_topic": false }, { "descriptor": "Polypodiaceae", "descriptor_ui": "D029621", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019", "date_precision": "year", "issue": "1", "normalized_date": "2019", "pages": "", "proceedings_title": null, "publisher": "", "title": "PLoS ONE", "volume": "14", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "Developmental analyses of divarications in leaves of an aquatic fern Microsorum pteropus and its varieties.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Medication-related osteonecrosis of the jaw (MRONJ) is a rare but serious adverse event of bone-modifying agents used to prevent bone complications in cancer patients with bone metastasis. Currently, early treatment is the only way to prevent further progression, as the pathogenesis of MRONJ has not yet been elucidated, and a standard treatment has not been established. The aim of this study was to identify a marker for early detection marker of MRONJ by exploring substances in saliva specific to MRONJ at an early stage. We collected salivary samples from 17 patients with MRONJ and conducted metabolomic analyses using capillary electrophoresis mass spectrometry for non-targeted analysis of hydrophilic metabolites. In the screening cohort, we compared the saliva of patients with stage >/=1 advanced MRONJ (n = 9) with that of controls without MRONJ before chemotherapy (n = 9). The top 5 most elevated salivary metabolites were histamine, 3-(4-hydroxyphenyl)propionate, malonate, carnosine, and hypotaurine. In the validation cohort, we analyzed additional patients with stage >/=1 advanced MRONJ (n = 8) and controls without MRONJ after chemotherapy (n = 9), confirming a significant 2.28-fold elevation in the salivary concentration of hypotaurine. These results revealed elevated salivary hypotaurine concentration as a potential marker for the early detection of MRONJ.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Wakako", "last_name": "Yatsuoka", "name": null }, { "creator_type": "author", "first_name": "Takao", "last_name": "Ueno", "name": null }, { "creator_type": "author", "first_name": "Kanako", "last_name": "Miyano", "name": null }, { "creator_type": "author", "first_name": "Yasuhito", "last_name": "Uezono", "name": null }, { "creator_type": "author", "first_name": "Ayame", "last_name": "Enomoto", "name": null }, { "creator_type": "author", "first_name": "Miku", "last_name": "Kaneko", "name": null }, { "creator_type": "author", "first_name": "Sana", "last_name": "Ota", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Sugimoto", "name": null }, { "creator_type": "author", "first_name": "Toshikazu", "last_name": "Ushijima", "name": null } ], "identifiers": { "doi": { "normalized": "10.1371/journal.pone.0220712" }, "pmcid": { "normalized": "PMC6690531" }, "pmid": { "normalized": "31404085" } }, "mesh": [ { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Biomarkers", "descriptor_ui": "D015415", "major_topic": false }, { "descriptor": "Bisphosphonate-Associated Osteonecrosis of the Jaw", "descriptor_ui": "D059266", "major_topic": false }, { "descriptor": "Case-Control Studies", "descriptor_ui": "D016022", "major_topic": false }, { "descriptor": "Electrophoresis, Capillary", "descriptor_ui": "D019075", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mass Spectrometry", "descriptor_ui": "D013058", "major_topic": false }, { "descriptor": "Metabolomics", "descriptor_ui": "D055432", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Saliva", "descriptor_ui": "D012463", "major_topic": false }, { "descriptor": "Taurine", "descriptor_ui": "D013654", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019", "date_precision": "year", "issue": "8", "normalized_date": "2019", "pages": "e0220712", "proceedings_title": null, "publisher": "", "title": "PloS one", "volume": "14", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "Metabolomic profiling reveals salivary hypotaurine as a potential early detection marker for medication-related osteonecrosis of the jaw.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Capillary electrophoresis-mass spectrometry (CE-MS) has been developed as a powerful tool in the analysis of charged compounds. To simultaneously analyze free amino acids, an electrolyte with low pH was used to positively charge all of the amino acids. In this condition, all protonated amino acids migrated toward the cathode in CE and then were sensitively and selectively detected by MS. This method is simple, rapid, and selective and could readily be applied to the analysis of free amino acids in various samples. In this chapter, the detailed procedure to analyze amino acids using CE-tandem mass spectrometry (MS/MS) is described.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Akiyoshi", "last_name": "Hirayama", "name": null }, { "creator_type": "author", "first_name": "Satsuki", "last_name": "Ikeda", "name": null }, { "creator_type": "author", "first_name": "Asako", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/978-1-4939-9639-1_23" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "31347127" } }, "mesh": [ { "descriptor": "Amino Acids", "descriptor_ui": "D000596", "major_topic": false }, { "descriptor": "Electrolytes", "descriptor_ui": "D004573", "major_topic": false }, { "descriptor": "Electrophoresis, Capillary", "descriptor_ui": "D019075", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Hydrogen-Ion Concentration", "descriptor_ui": "D006863", "major_topic": false }, { "descriptor": "Tandem Mass Spectrometry", "descriptor_ui": "D053719", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019", "date_precision": "year", "issue": "", "normalized_date": "2019", "pages": "307-313", "proceedings_title": null, "publisher": "", "title": "Methods in molecular biology (Clifton, N.J.)", "volume": "2030", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "Amino Acid Analysis by Capillary Electrophoresis-Mass Spectrometry.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Vascular smooth muscle cells (VSMCs) play critical roles in the stability and tonic regulation of vascular homeostasis. VSMCs can switch back and forth between highly proliferative synthetic and fully differentiated contractile phenotypes in response to changes in the vessel environment. Although abnormal phenotypic switching of VSMCs is a hallmark of vascular disorders such as atherosclerosis and restenosis after angioplasty, how control of VSMC phenotypic switching is dysregulated in pathologic conditions remains obscure. We found that inhibition of canonical transient receptor potential 6 (TRPC6) channels facilitated contractile differentiation of VSMCs through plasma membrane hyperpolarization. TRPC6-deficient VSMCs exhibited more polarized resting membrane potentials and higher protein kinase B (Akt) activity than wild-type VSMCs in response to TGF-beta1 stimulation. Ischemic stress elicited by oxygen-glucose deprivation suppressed TGF-beta1-induced hyperpolarization and VSMC differentiation, but this effect was abolished by TRPC6 deletion. TRPC6-mediated Ca(2+) influx and depolarization coordinately promoted the interaction of TRPC6 with lipid phosphatase and tensin homolog deleted from chromosome 10 (PTEN), a negative regulator of Akt activation. Given the marked up-regulation of TRPC6 observed in vascular disorders, our findings suggest that attenuation of TRPC6 channel activity in pathologic VSMCs could be a rational strategy to maintain vascular quality control by fine-tuning of VSMC phenotypic switching.-Numaga-Tomita, T., Shimauchi, T., Oda, S., Tanaka, T., Nishiyama, K., Nishimura, A., Birnbaumer, L., Mori, Y., Nishida, M. TRPC6 regulates phenotypic switching of vascular smooth muscle cells through plasma membrane potential-dependent coupling with PTEN.", "classifications": [ { "id": "Nishida", "label": "Group Nishida", "parent": "Nishida", "type": "group" }, { "id": "Nishimura", "label": "Group Nishimura", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Takuro", "last_name": "Numaga-Tomita", "name": null }, { "creator_type": "author", "first_name": "Tsukasa", "last_name": "Shimauchi", "name": null }, { "creator_type": "author", "first_name": "Sayaka", "last_name": "Oda", "name": null }, { "creator_type": "author", "first_name": "Tomohiro", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Kazuhiro", "last_name": "Nishiyama", "name": null }, { "creator_type": "author", "first_name": "Akiyuki", "last_name": "Nishimura", "name": null }, { "creator_type": "author", "first_name": "Lutz", "last_name": "Birnbaumer", "name": null }, { "creator_type": "author", "first_name": "Yasuo", "last_name": "Mori", "name": null }, { "creator_type": "author", "first_name": "Motohiro", "last_name": "Nishida", "name": null } ], "identifiers": { "doi": { "normalized": "10.1096/fj.201802811r" }, "pmcid": { "normalized": "PMC6704458" }, "pmid": { "normalized": "31162976" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Aorta", "descriptor_ui": "D001011", "major_topic": false }, { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "Cell Membrane", "descriptor_ui": "D002462", "major_topic": false }, { "descriptor": "Membrane Potentials", "descriptor_ui": "D008564", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Muscle, Smooth, Vascular", "descriptor_ui": "D009131", "major_topic": false }, { "descriptor": "Myocytes, Smooth Muscle", "descriptor_ui": "D032389", "major_topic": false }, { "descriptor": "Proto-Oncogene Proteins c-akt", "descriptor_ui": "D051057", "major_topic": false }, { "descriptor": "PTEN Phosphohydrolase", "descriptor_ui": "D051059", "major_topic": false }, { "descriptor": "TRPC6 Cation Channel", "descriptor_ui": "D000074287", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019 Sep", "date_precision": "unknown", "issue": "9", "normalized_date": null, "pages": "9785-9796", "proceedings_title": null, "publisher": "", "title": "FASEB journal : official publication of the Federation of American Societies for Experimental Biology", "volume": "33", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "TRPC6 regulates phenotypic switching of vascular smooth muscle cells through plasma membrane potential-dependent coupling with PTEN.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The diaphragm is driven by phrenic motoneurons that are located in the cervical spinal cord. Although the anatomical location of the phrenic nucleus and the function of phrenic motoneurons at a single cellular level have been extensively analyzed, the spatiotemporal dynamics of phrenic motoneuron group activity have not been fully elucidated. In the present study, we analyzed the functional and structural characteristics of respiratory neuron population in the cervical spinal cord at the level of the phrenic nucleus by voltage imaging, together with histological analysis of neuronal and astrocytic distribution in the cervical spinal cord. We found spatially distinct two cellular populations that exhibited synchronized inspiratory activity on the transversely cut plane at C4-C5 levels and on the ventral surface of the mid cervical spinal cord in the isolated brainstem-spinal cord preparation of the neonatal rat. Inspiratory activity of one group emerged in the central portion of the ventral horn that corresponded to the central motor column, and the other appeared in the medial portion of the ventral horn that corresponded to the medial motor column. We identified by retrogradely labeling study that the anatomical distributions of phrenic and scalene motoneurons coincided with optically detected central and medial motor regions, respectively. Furthermore, we anatomically demonstrated closely located features of putative motoneurons, interneurons and astrocytes in these regions. Collectively, we report that phrenic and scalene motoneuron populations show synchronized inspiratory activities with distinct anatomical locations in the mid cervical spinal cord.", "classifications": [ { "id": "Yokota", "label": "Group Yokota", "parent": "Enomoto", "type": "group" }, { "id": "Enomoto", "label": "Team Enomoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yoshio", "last_name": "Shinozaki", "name": null }, { "creator_type": "author", "first_name": "Shigefumi", "last_name": "Yokota", "name": null }, { "creator_type": "author", "first_name": "Fumikazu", "last_name": "Miwakeichi", "name": null }, { "creator_type": "author", "first_name": "Mieczyslaw", "last_name": "Pokorski", "name": null }, { "creator_type": "author", "first_name": "Ryoma", "last_name": "Aoyama", "name": null }, { "creator_type": "author", "first_name": "Kentaro", "last_name": "Fukuda", "name": null }, { "creator_type": "author", "first_name": "Hideaki", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Yoshiaki", "last_name": "Toyama", "name": null }, { "creator_type": "author", "first_name": "Masaya", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Yasumasa", "last_name": "Okada", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/s00429-018-1757-3" }, "pmcid": { "normalized": "PMC6373374" }, "pmid": { "normalized": "30251026" } }, "mesh": [ { "descriptor": "Action Potentials", "descriptor_ui": "D000200", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Animals, Newborn", "descriptor_ui": "D000831", "major_topic": false }, { "descriptor": "Brain Stem", "descriptor_ui": "D001933", "major_topic": false }, { "descriptor": "Cervical Cord", "descriptor_ui": "D066193", "major_topic": false }, { "descriptor": "Cervical Vertebrae", "descriptor_ui": "D002574", "major_topic": false }, { "descriptor": "Diaphragm", "descriptor_ui": "D003964", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "In Vitro Techniques", "descriptor_ui": "D066298", "major_topic": false }, { "descriptor": "Inhalation", "descriptor_ui": "D001239", "major_topic": true }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Motor Neurons", "descriptor_ui": "D009046", "major_topic": false }, { "descriptor": "Neural Pathways", "descriptor_ui": "D009434", "major_topic": false }, { "descriptor": "Neuroanatomical Tract-Tracing Techniques", "descriptor_ui": "D056347", "major_topic": false }, { "descriptor": "Rats, Wistar", "descriptor_ui": "D017208", "major_topic": false }, { "descriptor": "Time Factors", "descriptor_ui": "D013997", "major_topic": false }, { "descriptor": "Voltage-Sensitive Dye Imaging", "descriptor_ui": "D056969", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019 Jan", "date_precision": "unknown", "issue": "1", "normalized_date": null, "pages": "57-72", "proceedings_title": null, "publisher": "", "title": "Brain structure & function", "volume": "224", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "Structural and functional identification of two distinct inspiratory neuronal populations at the level of the phrenic nucleus in the rat cervical spinal cord.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Rho-associated, coiled-coil-containing protein kinase 1 might have applications as a potential therapeutic target for the treatment of non-alcoholic fatty liver disease.", "classifications": [ { "id": "Miyamoto", "label": "Group Miyamoto", "parent": "Wakamoto", "type": "group" }, { "id": "Wakamoto", "label": "Team Wakamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Takafumi", "last_name": "Miyamoto", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Matsuzaka", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Shimano", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/jdi.13051" }, "pmcid": { "normalized": "PMC6717821" }, "pmid": { "normalized": "30919598" } }, "mesh": [ { "descriptor": "AMP-Activated Protein Kinases", "descriptor_ui": "D055372", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Lipogenesis", "descriptor_ui": "D050155", "major_topic": false }, { "descriptor": "Liver", "descriptor_ui": "D008099", "major_topic": false }, { "descriptor": "Overnutrition", "descriptor_ui": "D044343", "major_topic": true }, { "descriptor": "rho-Associated Kinases", "descriptor_ui": "D054460", "major_topic": true } ], "publication": { "conference_name": null, "date": "2019 Sep", "date_precision": "unknown", "issue": "5", "normalized_date": null, "pages": "1165-1167", "proceedings_title": null, "publisher": "", "title": "Journal of diabetes investigation", "volume": "10", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "Rho-associated, coiled-coil-containing protein kinase 1 as a new player in the regulation of hepatic lipogenesis.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Protoporphyrin IX-fluorescence measurement is a powerful in situ approach for cancer detection after oral/topical administration of 5-aminolevulinic acid. However, this approach has not been clinically established for breast cancer, probably due to insufficient delivery of 5-aminolevulinic acid to the mammary glands. In the present study, we directly exposed breast cancer cells to 5-aminolevulinic acid to assess their discrimination via protoporphyrin IX-fluorescence. Fluorescence intensity (FI) was measured in the human breast cancer cell lines MCF7 and MDA-MB-231 and breast epithelial cell line MCF10A by confocal microscopy and flow cytometry. After 5-aminolevulinic acid exposure for 2 hours, protoporphyrin IX-FI in MCF7 and MDA-MB-231 cells significantly increased with marked cell-to-cell variability, whereas that in MCF10A cells increased moderately. Combined exposure of the cancer cells to 5-aminolevulinic acid and Ko143, a specific inhibitor of ATP-binding cassette transporter G2, further increased protoporphyrin IX-FI and alleviated the cell-to-cell variability in MCF7 and MDA-MB-231 cells, indicating improvement in the reproducibility and accuracy for fluorescence-based cancer detection. The increased FI by combined administration of these two drugs was also demonstrated in cells obtained via fine needle aspiration from mouse xenograft models inoculated with MDA-MB-231 cells. Furthermore, a cutoff value for increased protoporphyrin IX-FI ratio, before and after exposure to these drugs, clearly discriminated between cancer and noncancer cells. Taken together, direct exposure to 5-aminolevulinic acid and Ko143 may be a promising strategy for efficient fluorescence-based detection of breast cancer cells ex vivo using fine needle aspiration.", "classifications": [ { "id": "Tanaka", "label": "Group Tanaka", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Midori", "last_name": "Morita", "name": null }, { "creator_type": "author", "first_name": "Hideo", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Yasuaki", "last_name": "Kumamoto", "name": null }, { "creator_type": "author", "first_name": "Akihiro", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Yoshinori", "last_name": "Harada", "name": null }, { "creator_type": "author", "first_name": "Takehiro", "last_name": "Ogata", "name": null }, { "creator_type": "author", "first_name": "Koichi", "last_name": "Sakaguchi", "name": null }, { "creator_type": "author", "first_name": "Tetsuya", "last_name": "Taguchi", "name": null }, { "creator_type": "author", "first_name": "Tetsuro", "last_name": "Takamatsu", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/cam4.2466" }, "pmcid": { "normalized": "PMC6746108" }, "pmid": { "normalized": "31385432" } }, "mesh": [ { "descriptor": "Aminolevulinic Acid", "descriptor_ui": "D000622", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Biopsy, Fine-Needle", "descriptor_ui": "D044963", "major_topic": false }, { "descriptor": "Breast Neoplasms", "descriptor_ui": "D001943", "major_topic": false }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Diketopiperazines", "descriptor_ui": "D054659", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Heterocyclic Compounds, 4 or More Rings", "descriptor_ui": "D006576", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "MCF-7 Cells", "descriptor_ui": "D061986", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Microscopy, Confocal", "descriptor_ui": "D018613", "major_topic": false }, { "descriptor": "Protoporphyrins", "descriptor_ui": "D011524", "major_topic": false }, { "descriptor": "Xenograft Model Antitumor Assays", "descriptor_ui": "D023041", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019 Sep", "date_precision": "unknown", "issue": "12", "normalized_date": null, "pages": "5524-5533", "proceedings_title": null, "publisher": "", "title": "Cancer medicine", "volume": "8", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "Fluorescence-based discrimination of breast cancer cells by direct exposure to 5-aminolevulinic acid.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "In early lobe formation, basic proline-rich proteins associated with microtubules organize distinct microtubule arrays that are essential for lobe growth and a flattened cell shape in pavement cells.", "classifications": [ { "id": "Higaki", "label": "Group Higaki", "parent": "Ueda", "type": "group" }, { "id": "Ueda", "label": "Team Ueda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Jeh Haur", "last_name": "Wong", "name": null }, { "creator_type": "author", "first_name": "Takehide", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Samuel A.", "last_name": "Belteton", "name": null }, { "creator_type": "author", "first_name": "Rie", "last_name": "Shimizu", "name": null }, { "creator_type": "author", "first_name": "Nene", "last_name": "Kinoshita", "name": null }, { "creator_type": "author", "first_name": "Takumi", "last_name": "Higaki", "name": null }, { "creator_type": "author", "first_name": "Yuichi", "last_name": "Sakumura", "name": null }, { "creator_type": "author", "first_name": "Daniel B.", "last_name": "Szymanski", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Hashimoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1104/pp.19.00811" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "31601644" } }, "mesh": [ { "descriptor": "Anisotropy", "descriptor_ui": "D016880", "major_topic": false }, { "descriptor": "Arabidopsis", "descriptor_ui": "D017360", "major_topic": false }, { "descriptor": "Arabidopsis Proteins", "descriptor_ui": "D029681", "major_topic": false }, { "descriptor": "Cell Shape", "descriptor_ui": "D048430", "major_topic": true }, { "descriptor": "Cotyledon", "descriptor_ui": "D018548", "major_topic": false }, { "descriptor": "Microtubules", "descriptor_ui": "D008870", "major_topic": false }, { "descriptor": "Models, Biological", "descriptor_ui": "D008954", "major_topic": false }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": false }, { "descriptor": "Plant Cells", "descriptor_ui": "D059828", "major_topic": false }, { "descriptor": "Plant Leaves", "descriptor_ui": "D018515", "major_topic": false }, { "descriptor": "Subcellular Fractions", "descriptor_ui": "D013347", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019 Dec", "date_precision": "unknown", "issue": "4", "normalized_date": null, "pages": "1535-1551", "proceedings_title": null, "publisher": "", "title": "Plant Physiology", "volume": "181", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "Basic Proline-Rich Protein-Mediated Microtubules Are Essential for Lobe Growth and Flattened Cell Geometry1.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Notch signaling plays pivotal roles in both hematopoietic stem/progenitor and their niche cells. Myeloproliferative phenotypes are induced by disruption of Notch signaling in nonhematopoietic bone marrow (BM) cells. Nestin-expressing cells in the BM reportedly represent a component of the hematopoietic stem cell niche. We established mice in which rare Nestin-expressing cells in the BM were marked by green fluorescent protein, and Notch signaling was conditionally disrupted in these cells specifically. We observed impairment of erythropoiesis in the BM accompanying splenomegaly with BM hematopoietic programs in other lineages undisturbed. Transplantation experiments revealed that the microenvironmental rather than the hematopoietic cells were attributable to these phenotypes. We further found that the erythroid-island-forming ability of BM central macrophages was compromised along with the transcriptional upregulation of interleukin-6. Various Inflammatory conditions hamper BM erythropoiesis, which often accompanies extramedullary hematopoiesis. The mouse model demonstrated here may be of relevance to this common pathophysiologic condition. Stem Cells 2019;37:924-936.", "classifications": [ { "id": "Nishikii", "label": "Group Nishikii", "parent": "Shintaku", "type": "group" }, { "id": "Shintaku", "label": "Team Shintaku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Tatsuhiro", "last_name": "Sakamoto", "name": null }, { "creator_type": "author", "first_name": "Naoshi", "last_name": "Obara", "name": null }, { "creator_type": "author", "first_name": "Hidekazu", "last_name": "Nishikii", "name": null }, { "creator_type": "author", "first_name": "Takayasu", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Luan", "last_name": "Cao-Sy", "name": null }, { "creator_type": "author", "first_name": "Ryosuke", "last_name": "Fujimura", "name": null }, { "creator_type": "author", "first_name": "Hideo", "last_name": "Yagita", "name": null }, { "creator_type": "author", "first_name": "Mamiko", "last_name": "Sakata-Yanagimoto", "name": null }, { "creator_type": "author", "first_name": "Satoru", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Shigeru", "last_name": "Chiba", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/stem.3011" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "30932281" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Bone Marrow", "descriptor_ui": "D001853", "major_topic": false }, { "descriptor": "Bone Marrow Cells", "descriptor_ui": "D001854", "major_topic": false }, { "descriptor": "Cell Lineage", "descriptor_ui": "D019070", "major_topic": false }, { "descriptor": "Erythropoiesis", "descriptor_ui": "D004920", "major_topic": false }, { "descriptor": "Gene Expression Regulation", "descriptor_ui": "D005786", "major_topic": false }, { "descriptor": "Genes, Reporter", "descriptor_ui": "D017930", "major_topic": false }, { "descriptor": "Green Fluorescent Proteins", "descriptor_ui": "D049452", "major_topic": false }, { "descriptor": "Interleukin-6", "descriptor_ui": "D015850", "major_topic": false }, { "descriptor": "Macrophages", "descriptor_ui": "D008264", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Transgenic", "descriptor_ui": "D008822", "major_topic": false }, { "descriptor": "Nestin", "descriptor_ui": "D064231", "major_topic": false }, { "descriptor": "Receptors, Notch", "descriptor_ui": "D051880", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Splenomegaly", "descriptor_ui": "D013163", "major_topic": false }, { "descriptor": "Stem Cell Niche", "descriptor_ui": "D055153", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019 Jul", "date_precision": "unknown", "issue": "7", "normalized_date": null, "pages": "924-936", "proceedings_title": null, "publisher": "", "title": "Stem cells (Dayton, Ohio)", "volume": "37", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "Notch Signaling in Nestin-Expressing Cells in the Bone Marrow Maintains Erythropoiesis via Macrophage Integrity.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Genome-wide CRISPR/Cas9 knockout screens are revolutionizing mammalian functional genomics. However, their range of applications remains limited by signal variability from different guide RNAs that target the same gene, which confounds gene effect estimation and dictates large experiment sizes. To address this problem, we report JACKS, a Bayesian method that jointly analyzes screens performed with the same guide RNA library. Modeling the variable guide efficacies greatly improves hit identification over processing a single screen at a time and outperforms existing methods. This more efficient analysis gives additional hits and allows designing libraries with a 2.5-fold reduction in required cell numbers without sacrificing performance compared to current analysis standards.", "classifications": [ { "id": "Yusa", "label": "Group Yusa", "parent": "Eiraku", "type": "group" }, { "id": "Eiraku", "label": "Team Eiraku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Felicity", "last_name": "Allen", "name": null }, { "creator_type": "author", "first_name": "Fiona", "last_name": "Behan", "name": null }, { "creator_type": "author", "first_name": "Anton", "last_name": "Khodak", "name": null }, { "creator_type": "author", "first_name": "Francesco", "last_name": "Iorio", "name": null }, { "creator_type": "author", "first_name": "Kosuke", "last_name": "Yusa", "name": null }, { "creator_type": "author", "first_name": "Mathew", "last_name": "Garnett", "name": null }, { "creator_type": "author", "first_name": "Leopold", "last_name": "Parts", "name": null } ], "identifiers": { "doi": { "normalized": "10.1101/gr.238923.118" }, "pmcid": { "normalized": "PMC6396427" }, "pmid": { "normalized": "30674557" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Bayes Theorem", "descriptor_ui": "D001499", "major_topic": false }, { "descriptor": "CRISPR-Cas Systems", "descriptor_ui": "D064113", "major_topic": true }, { "descriptor": "Gene Knockout Techniques", "descriptor_ui": "D055786", "major_topic": false }, { "descriptor": "Software", "descriptor_ui": "D012984", "major_topic": true } ], "publication": { "conference_name": null, "date": "2019 Mar", "date_precision": "unknown", "issue": "3", "normalized_date": null, "pages": "464-471", "proceedings_title": null, "publisher": "", "title": "Genome research", "volume": "29", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "JACKS: joint analysis of CRISPR/Cas9 knockout screens.", "url": "https://riken-share.ent.box.com/folder/380763181239", "zotero": { "item_type": "journalArticle" } }, { "abstract": "In many cancers, high proliferation rates correlate with elevation of rRNA and tRNA levels, and nucleolar hypertrophy. However, the underlying mechanisms linking increased nucleolar transcription and tumorigenesis are only minimally understood. Here we show that IMP dehydrogenase-2 (IMPDH2), the rate-limiting enzyme for de novo guanine nucleotide biosynthesis, is overexpressed in the highly lethal brain cancer glioblastoma. This leads to increased rRNA and tRNA synthesis, stabilization of the nucleolar GTP-binding protein nucleostemin, and enlarged, malformed nucleoli. Pharmacological or genetic inactivation of IMPDH2 in glioblastoma reverses these effects and inhibits cell proliferation, whereas untransformed glia cells are unaffected by similar IMPDH2 perturbations. Impairment of IMPDH2 activity triggers nucleolar stress and growth arrest of glioblastoma cells even in the absence of functional p53. Our results reveal that upregulation of IMPDH2 is a prerequisite for the occurance of aberrant nucleolar function and increased anabolic processes in glioblastoma, which constitutes a primary event in gliomagenesis.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Satoshi", "last_name": "Kofuji", "name": null }, { "creator_type": "author", "first_name": "Akiyoshi", "last_name": "Hirayama", "name": null }, { "creator_type": "author", "first_name": "Alexander Otto", "last_name": "Eberhardt", "name": null }, { "creator_type": "author", "first_name": "Risa", "last_name": "Kawaguchi", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Sugiura", "name": null }, { "creator_type": "author", "first_name": "Oltea", "last_name": "Sampetrean", "name": null }, { "creator_type": "author", "first_name": "Yoshiki", "last_name": "Ikeda", "name": null }, { "creator_type": "author", "first_name": "Mikako", "last_name": "Warren", "name": null }, { "creator_type": "author", "first_name": "Naoya", "last_name": "Sakamoto", "name": null }, { "creator_type": "author", "first_name": "Shuji", "last_name": "Kitahara", "name": null }, { "creator_type": "author", "first_name": "Hirofumi", "last_name": "Yoshino", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Yamashita", "name": null }, { "creator_type": "author", "first_name": "Kazutaka", "last_name": "Sumita", "name": null }, { "creator_type": "author", "first_name": "Kara", "last_name": "Wolfe", "name": null }, { "creator_type": "author", "first_name": "Lisa", "last_name": "Lange", "name": null }, { "creator_type": "author", "first_name": "Satsuki", "last_name": "Ikeda", "name": null }, { "creator_type": "author", "first_name": "Hiroko", "last_name": "Shimada", "name": null }, { "creator_type": "author", "first_name": "Noriaki", "last_name": "Minami", "name": null }, { "creator_type": "author", "first_name": "Akshiv", "last_name": "Malhotra", "name": null }, { "creator_type": "author", "first_name": "Shin", "last_name": "Morioka", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Ban", "name": null }, { "creator_type": "author", "first_name": "Maya", "last_name": "Asano", "name": null }, { "creator_type": "author", "first_name": "Victoria L.", "last_name": "Flanary", "name": null }, { "creator_type": "author", "first_name": "Annmarie", "last_name": "Ramkissoon", "name": null }, { "creator_type": "author", "first_name": "Lionel M. L.", "last_name": "Chow", "name": null }, { "creator_type": "author", "first_name": "Juri", "last_name": "Kiyokawa", "name": null }, { "creator_type": "author", "first_name": "Tomoyuki", "last_name": "Mashimo", "name": null }, { "creator_type": "author", "first_name": "Greg", "last_name": "Lucey", "name": null }, { "creator_type": "author", "first_name": "Sergey", "last_name": "Mareninov", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Ozawa", "name": null }, { "creator_type": "author", "first_name": "Nobuyuki", "last_name": "Onishi", "name": null }, { "creator_type": "author", "first_name": "Koichi", "last_name": "Okumura", "name": null }, { "creator_type": "author", "first_name": "Jumpei", "last_name": "Terakawa", "name": null }, { "creator_type": "author", "first_name": "Takiko", "last_name": "Daikoku", "name": null }, { "creator_type": "author", "first_name": "Trisha", "last_name": "Wise-Draper", "name": null }, { "creator_type": "author", "first_name": "Nazanin", "last_name": "Majd", "name": null }, { "creator_type": "author", "first_name": "Kaori", "last_name": "Kofuji", "name": null }, { "creator_type": "author", "first_name": "Mika", "last_name": "Sasaki", "name": null }, { "creator_type": "author", "first_name": "Masaru", "last_name": "Mori", "name": null }, { "creator_type": "author", "first_name": "Yonehiro", "last_name": "Kanemura", "name": null }, { "creator_type": "author", "first_name": "Eric P.", "last_name": "Smith", "name": null }, { "creator_type": "author", "first_name": "Dimitrios", "last_name": "Anastasiou", "name": null }, { "creator_type": "author", "first_name": "Hiroaki", "last_name": "Wakimoto", "name": null }, { "creator_type": "author", "first_name": "Eric C.", "last_name": "Holland", "name": null }, { "creator_type": "author", "first_name": "William H.", "last_name": "Yong", "name": null }, { "creator_type": "author", "first_name": "Craig", "last_name": "Horbinski", "name": null }, { "creator_type": "author", "first_name": "Ichiro", "last_name": "Nakano", "name": null }, { "creator_type": "author", "first_name": "Ralph J.", "last_name": "DeBerardinis", "name": null }, { "creator_type": "author", "first_name": "Robert M.", "last_name": "Bachoo", "name": null }, { "creator_type": "author", "first_name": "Paul S.", "last_name": "Mischel", "name": null }, { "creator_type": "author", "first_name": "Wataru", "last_name": "Yasui", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Suematsu", "name": null }, { "creator_type": "author", "first_name": "Hideyuki", "last_name": "Saya", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Ingrid", "last_name": "Grummt", "name": null }, { "creator_type": "author", "first_name": "Holger", "last_name": "Bierhoff", "name": null }, { "creator_type": "author", "first_name": "Atsuo T.", "last_name": "Sasaki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41556-019-0363-9" }, "pmcid": { "normalized": "PMC6686884" }, "pmid": { "normalized": "31371825" } }, "mesh": [ { "descriptor": "Carcinogenesis", "descriptor_ui": "D063646", "major_topic": false }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Cell Nucleolus", "descriptor_ui": "D002466", "major_topic": false }, { "descriptor": "Cell Proliferation", "descriptor_ui": "D049109", "major_topic": false }, { "descriptor": "Cell Transformation, Neoplastic", "descriptor_ui": "D002471", "major_topic": false }, { "descriptor": "Glioblastoma", "descriptor_ui": "D005909", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "IMP Dehydrogenase", "descriptor_ui": "D007168", "major_topic": false }, { "descriptor": "RNA, Ribosomal", "descriptor_ui": "D012335", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019 Aug", "date_precision": "unknown", "issue": "8", "normalized_date": null, "pages": "1003-1014", "proceedings_title": null, "publisher": "", "title": "Nature cell biology", "volume": "21", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "IMP dehydrogenase-2 drives aberrant nucleolar activity and promotes tumorigenesis in glioblastoma.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "AIM: To develop a population-based statistical model in order to find a spatial pattern of dose distribution which is related to lower urinary tract symptoms (LUTS) after iodine-125 ((125)I) seed implantation for prostate cancer. PATIENTS AND METHODS: A total of 75 patients underwent (125)I seed implantation for prostate cancer. Principal component analysis was applied to the standardized dose array and for each patient dose distribution was uniquely characterized by a combination of weighted eigenvectors. The correlation between eigenvectors and the severity of LUTS was investigated with linear regression analysis. RESULTS: Eight eigenvectors were identified as being significantly associated with the severity of LUTS (p<0.05). Multivariate regression model identified that intraprostatic parameters, which were positively associated with the severity of LUTS, were distributed around a portion of the urethral base and a peripheral region of the prostate. CONCLUSION: We established a population-based statistical model that may indicate a significant dose pattern associated with the severity of radiation toxicity.", "classifications": [ { "id": "Hamamoto", "label": "Group Hamamoto", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Kazuma", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Naoya", "last_name": "Murakami", "name": null }, { "creator_type": "author", "first_name": "Kana", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Inaba", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Igaki", "name": null }, { "creator_type": "author", "first_name": "Ryuji", "last_name": "Hamamoto", "name": null }, { "creator_type": "author", "first_name": "Jun", "last_name": "Itami", "name": null } ], "identifiers": { "doi": { "normalized": "10.21873/invivo.11710" }, "pmcid": { "normalized": "PMC6899147" }, "pmid": { "normalized": "31662544" } }, "mesh": [ { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Aged, 80 and over", "descriptor_ui": "D000369", "major_topic": false }, { "descriptor": "Algorithms", "descriptor_ui": "D000465", "major_topic": false }, { "descriptor": "Biological Variation, Individual", "descriptor_ui": "D000076103", "major_topic": false }, { "descriptor": "Brachytherapy", "descriptor_ui": "D001918", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Iodine Radioisotopes", "descriptor_ui": "D007457", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Models, Statistical", "descriptor_ui": "D015233", "major_topic": true }, { "descriptor": "Neoplasm Grading", "descriptor_ui": "D060787", "major_topic": false }, { "descriptor": "Neoplasm Staging", "descriptor_ui": "D009367", "major_topic": false }, { "descriptor": "Prostatic Neoplasms", "descriptor_ui": "D011471", "major_topic": false }, { "descriptor": "Radiation Tolerance", "descriptor_ui": "D011836", "major_topic": true }, { "descriptor": "Radiotherapy Dosage", "descriptor_ui": "D011879", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019 Nov-Dec", "date_precision": "unknown", "issue": "6", "normalized_date": null, "pages": "2103-2111", "proceedings_title": null, "publisher": "", "title": "In vivo (Athens, Greece)", "volume": "33", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "A Population-based Statistical Model for Investigating Heterogeneous Intraprostatic Sensitivity to Radiation Toxicity After (125)I Seed Implantation.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Tumor recurrence is attributable to cancer stem-like cells (CSCs), the metabolic mechanisms of which currently remain obscure. Here, we uncovered the critical role of folate-mediated one-carbon (1C) metabolism involving mitochondrial methylenetetrahydrofolate dehydrogenase 2 (MTHFD2) and its downstream purine synthesis pathway. MTHFD2 knockdown greatly reduced tumorigenesis and stem-like properties, which were associated with purine nucleotide deficiency, and caused marked accumulation of 5-aminoimidazole carboxamide ribonucleotide (AICAR)-the final intermediate of the purine synthesis pathway. Lung cancer cells with acquired resistance to the targeted drug gefitinib, caused by elevated expression of components of the beta-catenin pathway, exhibited increased stem-like properties and enhanced expression of MTHFD2. MTHFD2 knockdown or treatment with AICAR reduced the stem-like properties and restored gefitinib sensitivity in these gefitinib-resistant cancer cells. Moreover, overexpression of MTHFD2 in gefitinib-sensitive lung cancer cells conferred resistance to gefitinib. Thus, MTHFD2-mediated mitochondrial 1C metabolism appears critical for cancer stem-like properties and resistance to drugs including gefitinib through consumption of AICAR, leading to depletion of the intracellular pool of AICAR. Because CSCs are dependent on MTHFD2, therapies targeting MTHFD2 may eradicate tumors and prevent recurrence.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Tatsunori", "last_name": "Nishimura", "name": null }, { "creator_type": "author", "first_name": "Asuka", "last_name": "Nakata", "name": null }, { "creator_type": "author", "first_name": "Xiaoxi", "last_name": "Chen", "name": null }, { "creator_type": "author", "first_name": "Kurumi", "last_name": "Nishi", "name": null }, { "creator_type": "author", "first_name": "Makiko", "last_name": "Meguro-Horike", "name": null }, { "creator_type": "author", "first_name": "Soichiro", "last_name": "Sasaki", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Kita", "name": null }, { "creator_type": "author", "first_name": "Shin-Ichi", "last_name": "Horike", "name": null }, { "creator_type": "author", "first_name": "Kaori", "last_name": "Saitoh", "name": null }, { "creator_type": "author", "first_name": "Keiko", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Kaori", "last_name": "Igarashi", "name": null }, { "creator_type": "author", "first_name": "Takahiko", "last_name": "Murayama", "name": null }, { "creator_type": "author", "first_name": "Susumu", "last_name": "Kohno", "name": null }, { "creator_type": "author", "first_name": "Chiaki", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Naofumi", "last_name": "Mukaida", "name": null }, { "creator_type": "author", "first_name": "Seiji", "last_name": "Yano", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Arinobu", "last_name": "Tojo", "name": null }, { "creator_type": "author", "first_name": "Noriko", "last_name": "Gotoh", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41388-018-0589-1" }, "pmcid": { "normalized": "PMC6484769" }, "pmid": { "normalized": "30532069" } }, "mesh": [ { "descriptor": "Aminohydrolases", "descriptor_ui": "D000619", "major_topic": false }, { "descriptor": "Aminoimidazole Carboxamide", "descriptor_ui": "D000620", "major_topic": false }, { "descriptor": "beta Catenin", "descriptor_ui": "D051176", "major_topic": false }, { "descriptor": "Carcinogenesis", "descriptor_ui": "D063646", "major_topic": false }, { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Drug Resistance, Neoplasm", "descriptor_ui": "D019008", "major_topic": false }, { "descriptor": "Folic Acid", "descriptor_ui": "D005492", "major_topic": false }, { "descriptor": "Gefitinib", "descriptor_ui": "D000077156", "major_topic": false }, { "descriptor": "Gene Expression Regulation, Neoplastic", "descriptor_ui": "D015972", "major_topic": false }, { "descriptor": "HEK293 Cells", "descriptor_ui": "D057809", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Lung Neoplasms", "descriptor_ui": "D008175", "major_topic": false }, { "descriptor": "Metabolic Networks and Pathways", "descriptor_ui": "D053858", "major_topic": false }, { "descriptor": "Methylenetetrahydrofolate Dehydrogenase (NADP)", "descriptor_ui": "D008754", "major_topic": false }, { "descriptor": "Mitochondria", "descriptor_ui": "D008928", "major_topic": false }, { "descriptor": "Multifunctional Enzymes", "descriptor_ui": "D064251", "major_topic": false }, { "descriptor": "Neoplasm Recurrence, Local", "descriptor_ui": "D009364", "major_topic": false }, { "descriptor": "Neoplastic Stem Cells", "descriptor_ui": "D014411", "major_topic": false }, { "descriptor": "Purines", "descriptor_ui": "D011687", "major_topic": false }, { "descriptor": "Ribonucleotides", "descriptor_ui": "D012265", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019 Apr", "date_precision": "unknown", "issue": "14", "normalized_date": null, "pages": "2464-2481", "proceedings_title": null, "publisher": "", "title": "Oncogene", "volume": "38", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "Cancer stem-like properties and gefitinib resistance are dependent on purine synthetic metabolism mediated by the mitochondrial enzyme MTHFD2.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "A defense mechanism in epithelial tissue can mechanically eliminate abnormal cells by contracting the cell boundary or area via actomyosin activity. From numerical simulations of the vertex dynamics model and approximate analytical solutions based on deviations from the ground state, here we derived general conditions for mechanical cell elimination (MCE) occurring via cell contraction. In particular, we found that MCE is realized by saddle-node bifurcation in a wide parameter range, and that the size of the eliminated cell is almost constant at the bifurcation point, suggesting the existence of an intrinsic threshold cell area for MCE.", "classifications": [ { "id": "Morishita", "label": "Group Morishita", "parent": "Morishita", "type": "group" }, { "id": "Morishita", "label": "Team Morishita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Sang-Woo", "last_name": "Lee", "name": null }, { "creator_type": "author", "first_name": "Yoshihiro", "last_name": "Morishita", "name": null } ], "identifiers": { "doi": { "normalized": "10.1103/physreve.100.032407" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "31640042" } }, "mesh": [ { "descriptor": "Biomechanical Phenomena", "descriptor_ui": "D001696", "major_topic": false }, { "descriptor": "Cell Size", "descriptor_ui": "D048429", "major_topic": true }, { "descriptor": "Epithelium", "descriptor_ui": "D004848", "major_topic": false }, { "descriptor": "Mechanical Phenomena", "descriptor_ui": "D055595", "major_topic": true }, { "descriptor": "Models, Biological", "descriptor_ui": "D008954", "major_topic": true } ], "publication": { "conference_name": null, "date": "2019 Sep", "date_precision": "unknown", "issue": "3-1", "normalized_date": null, "pages": "032407", "proceedings_title": null, "publisher": "", "title": "Physical review. E", "volume": "100", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "Critical contractility and cell size for mechanical cell elimination from epithelial tissue.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: The role of surgery in pancreatic neuroendocrine neoplasm grade 3 (pNEN-G3) treatment remains unclear. We aimed to clarify the role of surgery for pNEN-G3, which has recently been reclassified as pancreatic neuroendocrine tumor-G3 (pNET-G3) and pancreatic neuroendocrine carcinoma-G3 (pNEC-G3), with and without metastases, respectively. METHODS: We analyzed a subgroup of patients from the Japanese pancreatic NEC study, a Japanese multicenter case-series study of pNEN-G3. Pathologists subclassified 67 patients as having pNET-G3 or pNEC-G3 based on morphological features. We compared the overall survival (OS) rates among patients who were grouped according to whether they had undergone tumor-targeted surgery for tumors without (SwoM) or with (SwM) metastases, or non-surgical procedures (NS). RESULTS: Data from 21 patients with pNET-G3 (SwoM, n = 6; SwM, n = 5; NS, n = 10) and 46 patients with pNEC-G3 (SwoM, n = 8; SwM, n = 5; NS, n = 33) were analyzed. OS of patients with pNET-G3 was significantly longer after SwoM and SwM than with NS (p = 0.018 and p = 0.022). In contrast, OS did not significantly differ between either SwoM or SwM and NS (p = 0.093 and p = 0.489) among patients with pNEC-G3. CONCLUSION: The role of surgery should be considered separately for pNET-G3 and pNEC-G3. Although SwoM and SwM can be considered for pNET-G3, caution is advised before considering SwM and SwoM for pNEC-G3.", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Tsukasa", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Susumu", "last_name": "Hijioka", "name": null }, { "creator_type": "author", "first_name": "Waki", "last_name": "Hosoda", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Ueno", "name": null }, { "creator_type": "author", "first_name": "Masayuki", "last_name": "Furukawa", "name": null }, { "creator_type": "author", "first_name": "Noritoshi", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Masafumi", "last_name": "Ikeda", "name": null }, { "creator_type": "author", "first_name": "Tetsuhide", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Yuzo", "last_name": "Kodama", "name": null }, { "creator_type": "author", "first_name": "Chigusa", "last_name": "Morizane", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Notohara", "name": null }, { "creator_type": "author", "first_name": "Hiroki", "last_name": "Taguchi", "name": null }, { "creator_type": "author", "first_name": "Masayuki", "last_name": "Kitano", "name": null }, { "creator_type": "author", "first_name": "Kei", "last_name": "Yane", "name": null }, { "creator_type": "author", "first_name": "Yoshiaki", "last_name": "Tsuchiya", "name": null }, { "creator_type": "author", "first_name": "Izumi", "last_name": "Komoto", "name": null }, { "creator_type": "author", "first_name": "Hiroki", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Akihito", "last_name": "Tsuji", "name": null }, { "creator_type": "author", "first_name": "Syunpei", "last_name": "Hashigo", "name": null }, { "creator_type": "author", "first_name": "Tetsuya", "last_name": "Mine", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Kanno", "name": null }, { "creator_type": "author", "first_name": "Go", "last_name": "Murohisa", "name": null }, { "creator_type": "author", "first_name": "Katsuyuki", "last_name": "Miyabe", "name": null }, { "creator_type": "author", "first_name": "Tadayuki", "last_name": "Takagi", "name": null }, { "creator_type": "author", "first_name": "Nobutaka", "last_name": "Matayoshi", "name": null }, { "creator_type": "author", "first_name": "Masafumi", "last_name": "Sakaguchi", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Ishii", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Kojima", "name": null }, { "creator_type": "author", "first_name": "Keitaro", "last_name": "Matsuo", "name": null }, { "creator_type": "author", "first_name": "Hideyuki", "last_name": "Yoshitomi", "name": null }, { "creator_type": "author", "first_name": "Shoji", "last_name": "Nakamori", "name": null }, { "creator_type": "author", "first_name": "Hiroaki", "last_name": "Yanagimoto", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null }, { "creator_type": "author", "first_name": "Junji", "last_name": "Furuse", "name": null }, { "creator_type": "author", "first_name": "Nobumasa", "last_name": "Mizuno", "name": null } ], "identifiers": { "doi": { "normalized": "10.1245/s10434-019-07252-8" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "30863939" } }, "mesh": [ { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Aged, 80 and over", "descriptor_ui": "D000369", "major_topic": false }, { "descriptor": "Carcinoma, Neuroendocrine", "descriptor_ui": "D018278", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Follow-Up Studies", "descriptor_ui": "D005500", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Neoplasm Invasiveness", "descriptor_ui": "D009361", "major_topic": false }, { "descriptor": "Neoplasm Metastasis", "descriptor_ui": "D009362", "major_topic": false }, { "descriptor": "Neoplasm Staging", "descriptor_ui": "D009367", "major_topic": false }, { "descriptor": "Neuroendocrine Tumors", "descriptor_ui": "D018358", "major_topic": false }, { "descriptor": "Pancreatectomy", "descriptor_ui": "D010180", "major_topic": false }, { "descriptor": "Pancreatic Neoplasms", "descriptor_ui": "D010190", "major_topic": false }, { "descriptor": "Survival Rate", "descriptor_ui": "D015996", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019 May", "date_precision": "unknown", "issue": "5", "normalized_date": null, "pages": "1385-1393", "proceedings_title": null, "publisher": "", "title": "Annals of surgical oncology", "volume": "26", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "Surgery for Pancreatic Neuroendocrine Tumor G3 and Carcinoma G3 Should be Considered Separately.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Neuroblastoma, an embryonal tumor arising from the sympathetic ganglia and adrenal medulla, is among the most intractable pediatric cancers. Although a variety of genetic changes have been identified in neuroblastoma, how they contribute to its pathogenesis remains largely unclear. Recent studies have identified alterations of the anaplastic lymphoma kinase (ALK) gene in neuroblastoma; ALK F1174L (a phenylalanine-to-leucine substitution at codon 1174) represents one of the most frequent of these somatic mutations, and is associated with amplification of the MYCN gene, the most reliable marker for the poor survival. We engineered the mouse Alk locus so that ALK F1174L is expressed by its endogenous promoter and can be induced in a spatiotemporally controlled fashion using Cre-loxP system. Although expression of ALK F1174L resulted in enhanced proliferation of sympathetic ganglion progenitors and increased the size of the sympathetic ganglia, it was insufficient to cause neuroblastoma. However, lethal neuroblastoma frequently developed in mice co-expressing ALK F1174L and MYCN, even in a genetic background where MYCN alone does not cause overt tumors. These data reveal that physiological expression of ALK F1174L significantly potentiates the oncogenic ability of MYCN in vivo. Our conditional mutant mice provide a valuable platform for investigating the pathogenesis of neuroblastoma.", "classifications": [ { "id": "Enomoto", "label": "Group Enomoto", "parent": "Enomoto", "type": "group" }, { "id": "Enomoto", "label": "Team Enomoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Sachie", "last_name": "Ono", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Keita", "last_name": "Terui", "name": null }, { "creator_type": "author", "first_name": "Hideo", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Hideki", "last_name": "Enomoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/dvg.23323" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "31218818" } }, "mesh": [ { "descriptor": "Anaplastic Lymphoma Kinase", "descriptor_ui": "D000077548", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Carcinogenesis", "descriptor_ui": "D063646", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Ganglia, Sympathetic", "descriptor_ui": "D005728", "major_topic": false }, { "descriptor": "Genetic Engineering", "descriptor_ui": "D005818", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Mutant Strains", "descriptor_ui": "D008817", "major_topic": false }, { "descriptor": "Mutagenesis, Insertional", "descriptor_ui": "D016254", "major_topic": false }, { "descriptor": "N-Myc Proto-Oncogene Protein", "descriptor_ui": "D000071447", "major_topic": false }, { "descriptor": "Neoplasms, Experimental", "descriptor_ui": "D009374", "major_topic": false }, { "descriptor": "Neuroblastoma", "descriptor_ui": "D009447", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019 Oct", "date_precision": "unknown", "issue": "10", "normalized_date": null, "pages": "e23323", "proceedings_title": null, "publisher": "", "title": "Genesis (New York, N.Y. : 2000)", "volume": "57", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "Generation of conditional ALK F1174L mutant mouse models for the study of neuroblastoma pathogenesis.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Because of the ability to recapitulate normal developmental processes, brain organoids derived from pluripotent stem cells are an important experimental resource to investigate the development and pathogenesis of human brains. Although brain organoids are used in research on diseases such as microcephaly, it has traditionally been difficult to analyze diseases that affect neuronal networks between distant brain regions, as effective brain organoids containing multiple brain regions with defined connectivity have yet to be established. In this review, we discuss strategies to construct such organoids and provide a review on recent progress on brain organoids.", "classifications": [ { "id": "Eiraku", "label": "Group Eiraku", "parent": "Eiraku", "type": "group" }, { "id": "Eiraku", "label": "Team Eiraku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yusuke", "last_name": "Seto", "name": null }, { "creator_type": "author", "first_name": "Mototsugu", "last_name": "Eiraku", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.ceb.2019.07.010" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "31425932" } }, "mesh": [ { "descriptor": "Brain", "descriptor_ui": "D001921", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Organoids", "descriptor_ui": "D009940", "major_topic": false }, { "descriptor": "Pluripotent Stem Cells", "descriptor_ui": "D039904", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019 Dec", "date_precision": "unknown", "issue": "", "normalized_date": null, "pages": "86-91", "proceedings_title": null, "publisher": "", "title": "Current opinion in cell biology", "volume": "61", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "Toward the formation of neural circuits in human brain organoids.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Physical exercise yields beneficial effects on all types of muscle cells, which are essential for the maintenance of cardiovascular homeostasis and good blood circulation. Daily moderate exercise increases systemic antioxidative capacity, which can lead to the prevention of the onset and progression of oxidative stress-related diseases. Therefore, exercise is now widely accepted as one of the best therapeutic strategies for the treatment of ischemic (hypoxic) diseases. Canonical transient receptor potential (TRPC) proteins are non-selective cation channels activated by mechanical stress and/or stimulation of phospholipase C-coupled surface receptors. TRPC channels, especially diacylglycerol-activated TRPC channels (TRPC3 and TRPC6; TRPC3/6), play a key role in the development of cardiovascular remodeling. We have recently found that physical interaction between TRPC3 and NADPH oxidase (Nox) 2 under hypoxic stress promotes Nox2-dependent reactive oxygen species (ROS) production and mediates rodent cardiac plasticity, and inhibition of the TRPC3-Nox2 protein complex results in enhancement of myocardial compliance and flexibility similar to that observed in exercise-treated hearts. In this review, we describe current understanding of the roles of TRPC channels in striated muscle (patho)physiology and propose that targeting TRPC-based protein complexes could be a new strategy to imitate exercise therapy.", "classifications": [ { "id": "Nishida", "label": "Group Nishida", "parent": "Nishida", "type": "group" }, { "id": "Nishimura", "label": "Group Nishimura", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Takuro", "last_name": "Numaga-Tomita", "name": null }, { "creator_type": "author", "first_name": "Sayaka", "last_name": "Oda", "name": null }, { "creator_type": "author", "first_name": "Kazuhiro", "last_name": "Nishiyama", "name": null }, { "creator_type": "author", "first_name": "Tomohiro", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Akiyuki", "last_name": "Nishimura", "name": null }, { "creator_type": "author", "first_name": "Motohiro", "last_name": "Nishida", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/s00424-018-2211-3" }, "pmcid": { "normalized": "PMC6515694" }, "pmid": { "normalized": "30298191" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Exercise", "descriptor_ui": "D015444", "major_topic": false }, { "descriptor": "Exercise Therapy", "descriptor_ui": "D005081", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Myocardium", "descriptor_ui": "D009206", "major_topic": false }, { "descriptor": "NADPH Oxidases", "descriptor_ui": "D019255", "major_topic": false }, { "descriptor": "Physical Conditioning, Animal", "descriptor_ui": "D010805", "major_topic": false }, { "descriptor": "Reactive Oxygen Species", "descriptor_ui": "D017382", "major_topic": false }, { "descriptor": "Transient Receptor Potential Channels", "descriptor_ui": "D050051", "major_topic": false }, { "descriptor": "Type C Phospholipases", "descriptor_ui": "D010738", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019 Mar", "date_precision": "unknown", "issue": "3", "normalized_date": null, "pages": "507-517", "proceedings_title": null, "publisher": "", "title": "Pflugers Archiv : European journal of physiology", "volume": "471", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "TRPC channels in exercise-mimetic therapy.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "An amendment to this paper has been published and can be accessed via a link at the top of the paper.", "classifications": [ { "id": "Higaki", "label": "Group Higaki", "parent": "Ueda", "type": "group" }, { "id": "Ueda", "label": "Team Ueda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Tomoko", "last_name": "Hirano", "name": null }, { "creator_type": "author", "first_name": "Hiroki", "last_name": "Konno", "name": null }, { "creator_type": "author", "first_name": "Seiji", "last_name": "Takeda", "name": null }, { "creator_type": "author", "first_name": "Liam", "last_name": "Dolan", "name": null }, { "creator_type": "author", "first_name": "Mariko", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Aoyama", "name": null }, { "creator_type": "author", "first_name": "Takumi", "last_name": "Higaki", "name": null }, { "creator_type": "author", "first_name": "Hisako", "last_name": "Takigawa-Imamura", "name": null }, { "creator_type": "author", "first_name": "Masa H.", "last_name": "Sato", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41477-019-0416-x" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "30932014" } }, "mesh": [], "publication": { "conference_name": null, "date": "2019 Apr", "date_precision": "unknown", "issue": "4", "normalized_date": null, "pages": "447", "proceedings_title": null, "publisher": "", "title": "Nature plants", "volume": "5", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "Author Correction: PtdIns(3,5)P(2) mediates root hair shank hardening in Arabidopsis.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Jasmonic acid (JA) plays an important role in the induction of herbivore resistance in many plants. However, JA-independent herbivore resistance has been suggested. An herbivore-resistance-inducing substance was isolated from Tobacco mosaic virus-infected tobacco (Nicotiana tabacum) leaves in which a hypersensitive response (HR) was induced and identified as loliolide, which has been identified as a beta-carotene metabolite. When applied to tomato (Solanum lycopersicum) leaves, loliolide decreased the survival rate of the two-spotted spider mite, Tetranychus urticae, egg deposition by the same pest, and the survival rate of larvae of the common cutworm Spodoptera litura without exhibiting toxicity against these herbivores. Endogenous loliolide levels increased not only with an infestation by S litura larvae, but also with the exogenous application of their oral secretions in tomato. A microarray analysis identified cell-wall-associated defense genes as loliolide-responsive tomato genes, and exogenous JA application did not induce the expression of these genes. Suppressor of zeaxanthin-less (szl), an Arabidopsis (Arabidopsis thaliana) mutant with a point mutation in a key gene of the beta-carotene metabolic pathway, exhibited the decreased accumulation of endogenous loliolide and increased susceptibility to infestation by the western flower thrip (Frankliniella occidentalis). A pretreatment with loliolide decreased susceptibility to thrips in the JA-insensitive Arabidopsis mutant coronatine-insensitive1 Exogenous loliolide did not restore reduced electrolyte leakage in szl in response to a HR-inducing bacterial strain. These results suggest that loliolide functions as an endogenous signal that mediates defense responses to herbivores, possibly independently of JA, at least in tomato and Arabidopsis plants.", "classifications": [ { "id": "Mochizuki", "label": "Group Mochizuki", "parent": "Eiraku", "type": "group" }, { "id": "Eiraku", "label": "Team Eiraku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Mika", "last_name": "Murata", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Nakai", "name": null }, { "creator_type": "author", "first_name": "Kei", "last_name": "Kawazu", "name": null }, { "creator_type": "author", "first_name": "Masumi", "last_name": "Ishizaka", "name": null }, { "creator_type": "author", "first_name": "Hideyuki", "last_name": "Kajiwara", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Abe", "name": null }, { "creator_type": "author", "first_name": "Kasumi", "last_name": "Takeuchi", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Ichinose", "name": null }, { "creator_type": "author", "first_name": "Ichiro", "last_name": "Mitsuhara", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Mochizuki", "name": null }, { "creator_type": "author", "first_name": "Shigemi", "last_name": "Seo", "name": null } ], "identifiers": { "doi": { "normalized": "10.1104/pp.18.00837" }, "pmcid": { "normalized": "PMC6446782" }, "pmid": { "normalized": "30700538" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Arabidopsis", "descriptor_ui": "D017360", "major_topic": false }, { "descriptor": "Benzofurans", "descriptor_ui": "D001572", "major_topic": false }, { "descriptor": "Carotenoids", "descriptor_ui": "D002338", "major_topic": false }, { "descriptor": "Cell Death", "descriptor_ui": "D016923", "major_topic": false }, { "descriptor": "Herbivory", "descriptor_ui": "D060434", "major_topic": true }, { "descriptor": "Nicotiana", "descriptor_ui": "D014026", "major_topic": false }, { "descriptor": "Solanum lycopersicum", "descriptor_ui": "D018551", "major_topic": false }, { "descriptor": "Spodoptera", "descriptor_ui": "D018411", "major_topic": false }, { "descriptor": "Tetranychidae", "descriptor_ui": "D040102", "major_topic": false }, { "descriptor": "Tobacco Mosaic Virus", "descriptor_ui": "D014027", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019 Apr", "date_precision": "unknown", "issue": "4", "normalized_date": null, "pages": "1822-1833", "proceedings_title": null, "publisher": "", "title": "Plant physiology", "volume": "179", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "Loliolide, a Carotenoid Metabolite, Is a Potential Endogenous Inducer of Herbivore Resistance.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The physiological importance of reactive sulfur species (RSS) such as cysteine hydropersulfide (CysSSH) has been increasingly recognized in recent years. We have established a reactive sulfur metabolomics analysis by using RSS metabolic profiling, which revealed appreciable amounts of RSS generated endogenously and ubiquitously in both prokaryotic and eukaryotic organisms. The chemical nature of these polysulfides is not fully understood, however, because of their reactive or complicated redox-active properties. In our study here, we determined that tyrosine and a hydroxyphenyl-containing derivative, beta-(4-hydroxyphenyl)ethyl iodoacetamide (HPE-IAM), had potent stabilizing effects on diverse polysulfide residues formed in CysSSH-related low-molecular-weight species, e.g., glutathione polysulfides (oxidized glutathione trisulfide and oxidized glutathione tetrasulfide). The protective effect against degradation was likely caused by the inhibitory activity of hydroxyphenyl residues of tyrosine and HPE-IAM against alkaline hydrolysis of polysulfides. This hydrolysis occurred via heterolytic scission triggered by the hydroxyl anion acting on polysulfides that are cleaved into thiolates and sulfenic acids, with the hydrolysis being enhanced by alkylating reagents (e.g. IAM) and dimedone. Moreover, tyrosine prevented electrophilic degradation occurring in alkaline pH. The polysulfide stabilization induced by tyrosine or the hydroxyphenyl moiety of HPE-IAM will greatly improve our understanding of the chemical properties of polysulfides and may benefit the sulfur metabolomics analysis if it can be applied successfully to any kind of biological samples, including clinical specimens.", "classifications": [ { "id": "Akaike", "label": "Group Akaike", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Hisyam Abdul", "last_name": "Hamid", "name": null }, { "creator_type": "author", "first_name": "Akira", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Tomoaki", "last_name": "Ida", "name": null }, { "creator_type": "author", "first_name": "Akira", "last_name": "Nishimura", "name": null }, { "creator_type": "author", "first_name": "Tetsuro", "last_name": "Matsunaga", "name": null }, { "creator_type": "author", "first_name": "Shigemoto", "last_name": "Fujii", "name": null }, { "creator_type": "author", "first_name": "Masanobu", "last_name": "Morita", "name": null }, { "creator_type": "author", "first_name": "Tomohiro", "last_name": "Sawa", "name": null }, { "creator_type": "author", "first_name": "Jon M.", "last_name": "Fukuto", "name": null }, { "creator_type": "author", "first_name": "Peter", "last_name": "Nagy", "name": null }, { "creator_type": "author", "first_name": "Ryouhei", "last_name": "Tsutsumi", "name": null }, { "creator_type": "author", "first_name": "Hozumi", "last_name": "Motohashi", "name": null }, { "creator_type": "author", "first_name": "Hideshi", "last_name": "Ihara", "name": null }, { "creator_type": "author", "first_name": "Takaaki", "last_name": "Akaike", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.redox.2019.101096" }, "pmcid": { "normalized": "PMC6327103" }, "pmid": { "normalized": "30634125" } }, "mesh": [ { "descriptor": "Chromatography, Liquid", "descriptor_ui": "D002853", "major_topic": false }, { "descriptor": "Glutathione", "descriptor_ui": "D005978", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Metabolome", "descriptor_ui": "D055442", "major_topic": true }, { "descriptor": "Metabolomics", "descriptor_ui": "D055432", "major_topic": true }, { "descriptor": "Oxidation-Reduction", "descriptor_ui": "D010084", "major_topic": false }, { "descriptor": "Reactive Oxygen Species", "descriptor_ui": "D017382", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Sulfides", "descriptor_ui": "D013440", "major_topic": false }, { "descriptor": "Sulfur", "descriptor_ui": "D013455", "major_topic": false }, { "descriptor": "Tandem Mass Spectrometry", "descriptor_ui": "D053719", "major_topic": false }, { "descriptor": "Tyrosine", "descriptor_ui": "D014443", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019 Feb", "date_precision": "unknown", "issue": "", "normalized_date": null, "pages": "101096", "proceedings_title": null, "publisher": "", "title": "Redox biology", "volume": "21", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "Polysulfide stabilization by tyrosine and hydroxyphenyl-containing derivatives that is important for a reactive sulfur metabolomics analysis.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Mutual information and its causal variant, directed information, have been widely used to quantitatively characterize the performance of biological sensing and information transduction. However, once coupled with selection in response to decision-making, the sensing signal could have more or less evolutionary value than its mutual or directed information. In this work, we show that an individually sensed signal always has a better fitness value, on average, than its mutual or directed information. The fitness gain, which satisfies fluctuation relations (FRs), is attributed to the selection of organisms in a population that obtain a better sensing signal by chance. A new quantity, similar to the coarse-grained entropy production in information thermodynamics, is introduced to quantify the total fitness gain from individual sensing, which also satisfies FRs. Using this quantity, the optimizing fitness gain of individual sensing is shown to be related to fidelity allocations for individual environmental histories. Our results are supplemented by numerical verifications of FRs, and a discussion on how this problem is linked to information encoding and decoding.", "classifications": [ { "id": "JPMJCR1927", "label": "JPMJCR1927", "researcher": "Yuichi Wakamoto", "type": "grant" }, { "id": "Kobayashi", "label": "Group Kobayashi", "parent": "Wakamoto", "type": "group" }, { "id": "Wakamoto", "label": "Group Wakamoto", "parent": "Wakamoto", "type": "group" }, { "id": "Wakamoto", "label": "Team Wakamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Tetsuya J.", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Sughiyama", "name": null } ], "identifiers": { "doi": { "normalized": "10.3390/e21101002" }, "pmcid": { "normalized": "PMC7514213" }, "pmid": { "normalized": null } }, "mesh": [], "publication": { "conference_name": null, "date": "2019 Oct", "date_precision": "unknown", "issue": "10", "normalized_date": null, "pages": "", "proceedings_title": null, "publisher": "", "title": "Entropy", "volume": "21", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "Fitness Gain of Individually Sensed Information by Cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Molecular classifications of breast cancer (BRC), such as human epidermal growth factor receptor 2 (HER2), luminal A and luminal B, have been developed to reduce unnecessary treatment by dividing patients with BRC into low‑ and high‑risk progression groups. However, these methods do not cover all of the pathological characteristics of BRC, and investigations into novel prognostic/therapeutic markers are thus continually required. In this study, we identified the overexpression of the histone methyltransferase, euchromatic histone‑lysine N‑methyltransferase 2 (EHMT2) in BRC samples (n=1,222) and normal samples (n=113) derived from the TCGA portal by performing a BRC tissue microarray. EHMT2 overexpression was clearly associated with a poor prognosis in multiple cohorts of patients with BRC (total, n=1,644). Furthermore, the knockdown of EHMT2 expression affected cell apoptosis via the downregulation and re‑localization of heat shock protein family D (Hsp60) member 1 (HSPD1). In addition, a statistically significant positive correlation between EHMT2 and HSPD1 expression was revealed in the clinical cohorts. On the whole, the findings of this study may assist the development of novel therapeutic strategies and provide a prognostic marker (EHMT2) for patients with BRC.", "classifications": [ { "id": "Hamamoto", "label": "Group Hamamoto", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Seon-Kyu", "last_name": "Kim", "name": null }, { "creator_type": "author", "first_name": "Kwangho", "last_name": "Kim", "name": null }, { "creator_type": "author", "first_name": "Jea-Woon", "last_name": "Ryu", "name": null }, { "creator_type": "author", "first_name": "Tae-Young", "last_name": "Ryu", "name": null }, { "creator_type": "author", "first_name": "Jung Hwa", "last_name": "Lim", "name": null }, { "creator_type": "author", "first_name": "Jung-Hwa", "last_name": "Oh", "name": null }, { "creator_type": "author", "first_name": "Jeong-Ki", "last_name": "Min", "name": null }, { "creator_type": "author", "first_name": "Cho-Rok", "last_name": "Jung", "name": null }, { "creator_type": "author", "first_name": "Ryuji", "last_name": "Hamamoto", "name": null }, { "creator_type": "author", "first_name": "Mi-Young", "last_name": "Son", "name": null }, { "creator_type": "author", "first_name": "Dae-Soo", "last_name": "Kim", "name": null }, { "creator_type": "author", "first_name": "Hyun-Soo", "last_name": "Cho", "name": null } ], "identifiers": { "doi": { "normalized": "10.3892/ijo.2018.4608" }, "pmcid": { "normalized": "PMC6254934" }, "pmid": { "normalized": "30365075" } }, "mesh": [ { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Aged, 80 and over", "descriptor_ui": "D000369", "major_topic": false }, { "descriptor": "Biomarkers, Tumor", "descriptor_ui": "D014408", "major_topic": false }, { "descriptor": "Breast Neoplasms", "descriptor_ui": "D001943", "major_topic": false }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Cell Proliferation", "descriptor_ui": "D049109", "major_topic": false }, { "descriptor": "Chaperonin 60", "descriptor_ui": "D018834", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Gene Expression Regulation, Neoplastic", "descriptor_ui": "D015972", "major_topic": false }, { "descriptor": "Histocompatibility Antigens", "descriptor_ui": "D006649", "major_topic": false }, { "descriptor": "Histone-Lysine N-Methyltransferase", "descriptor_ui": "D011495", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "MCF-7 Cells", "descriptor_ui": "D061986", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Mitochondrial Proteins", "descriptor_ui": "D024101", "major_topic": false }, { "descriptor": "Prognosis", "descriptor_ui": "D011379", "major_topic": false }, { "descriptor": "Survival Analysis", "descriptor_ui": "D016019", "major_topic": false }, { "descriptor": "Up-Regulation", "descriptor_ui": "D015854", "major_topic": true } ], "publication": { "conference_name": null, "date": "2019 Jan", "date_precision": "unknown", "issue": "1", "normalized_date": null, "pages": "65-76", "proceedings_title": null, "publisher": "", "title": "International journal of oncology", "volume": "54", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "The novel prognostic marker, EHMT2, is involved in cell proliferation via HSPD1 regulation in breast cancer.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "PURPOSE: This study aimed to determine the correlation between DNA repair enzyme O6-methylguanine DNA methyltransferase (MGMT) status and the response to streptozocin in advanced well-differentiated pancreatic neuroendocrine tumors (WD panNETs). METHODS: To test the hypothesis that MGMT deficiency was required for an alkylating drug response, we retrospectively reviewed the response of 13 patients with WD panNETs to alkylating agents in relation to MGMT status. We also studied MGMT expression in streptozocin resistance using panNET cell lines. RESULTS: The cohort included 54% of patients with and 46% without MGMT expression. Among these, 83.3% (5/6) of MGMT-negative cases showed a partial response to streptozocin. In contrast, only 14.2% (1/7) of MGMT-positive cases showed a partial response (P = 0.013). Induced expression of MGMT in BON1 cells (a panNET cell line with undetectable endogenous MGMT) produced streptozocin resistance. Knockdown of MGMT in QGP1 cells, which express MGMT endogenously, did not alter the response to streptozocin. CONCLUSIONS: We observed a relationship between MGMT status and streptozocin response in both patients and cell culture. Despite limited cases examined, high concordance of negative expression of MGMT and response to streptozocin treatment suggest that MGMT expression can be a potential biomarker for this treatment.", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Susumu", "last_name": "Hijioka", "name": null }, { "creator_type": "author", "first_name": "Keiichiro", "last_name": "Sakuma", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Aoki", "name": null }, { "creator_type": "author", "first_name": "Nobumasa", "last_name": "Mizuno", "name": null }, { "creator_type": "author", "first_name": "Takamichi", "last_name": "Kuwahara", "name": null }, { "creator_type": "author", "first_name": "Nozomi", "last_name": "Okuno", "name": null }, { "creator_type": "author", "first_name": "Kazuo", "last_name": "Hara", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/s00280-018-3700-y" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "30310970" } }, "mesh": [ { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Antibiotics, Antineoplastic", "descriptor_ui": "D000903", "major_topic": false }, { "descriptor": "Biomarkers, Tumor", "descriptor_ui": "D014408", "major_topic": false }, { "descriptor": "DNA Modification Methylases", "descriptor_ui": "D015254", "major_topic": false }, { "descriptor": "DNA Repair Enzymes", "descriptor_ui": "D045643", "major_topic": false }, { "descriptor": "Drug Resistance, Neoplasm", "descriptor_ui": "D019008", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Follow-Up Studies", "descriptor_ui": "D005500", "major_topic": false }, { "descriptor": "Gene Expression Regulation, Neoplastic", "descriptor_ui": "D015972", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "In Vitro Techniques", "descriptor_ui": "D066298", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Neuroendocrine Tumors", "descriptor_ui": "D018358", "major_topic": false }, { "descriptor": "Pancreatic Neoplasms", "descriptor_ui": "D010190", "major_topic": false }, { "descriptor": "Prognosis", "descriptor_ui": "D011379", "major_topic": false }, { "descriptor": "Retrospective Studies", "descriptor_ui": "D012189", "major_topic": false }, { "descriptor": "Streptozocin", "descriptor_ui": "D013311", "major_topic": false }, { "descriptor": "Survival Rate", "descriptor_ui": "D015996", "major_topic": false }, { "descriptor": "Tumor Cells, Cultured", "descriptor_ui": "D014407", "major_topic": false }, { "descriptor": "Tumor Suppressor Proteins", "descriptor_ui": "D025521", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019 Jan", "date_precision": "unknown", "issue": "1", "normalized_date": null, "pages": "43-52", "proceedings_title": null, "publisher": "", "title": "Cancer chemotherapy and pharmacology", "volume": "83", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "Clinical and in vitro studies of the correlation between MGMT and the effect of streptozocin in pancreatic NET.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "OBJECTIVES: Perioperative nutritional management is essential for early recovery after liver surgery. The aim of this study was to assess changes in amino acid levels in serum and urine after hepatectomy. METHODS: Serum samples were collected from 16 patients with hepatocellular carcinoma before and 1, 3, and 14 d after hepatectomy (S0, S1, S3, and S14, respectively). Spot urine samples were collected before and 3 d after the hepatectomy (U0 and U3). Metabolites in the serum and urine were analyzed. RESULTS: Compared with S0, insulin levels significantly increased in the S1 and S3 samples. Valine levels significantly decreased in S1 and S14, and leucine levels significantly decreased in S14. Phenylalanine levels significantly increased in S1 and S3, and tyrosine levels significantly increased in S1. The Fischer ratio (branched-chain/aromatic amino acids) significantly decreased in S1 and S3. In multiple regression analysis, changes in serum taurine levels were related to the white blood cell count in S1 and S3, and inversely related to alanine aminotransferase levels in S14. Changes in serum glutamine levels were negatively related to C-reactive protein levels in S3. Serum glutamine levels decreased in S3 and S14, and tended to increase in U3, suggesting a deficiency of glutamate resulting from the invasive surgical procedure. CONCLUSIONS: These findings highlight the usefulness of metabolome analysis for characterizing perioperative patterns after liver resection. The observed amino acid pattern, including the reduction in Fischer ratio, underscores the need for specialized nutritional support.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Daisuke", "last_name": "Kajiura", "name": null }, { "creator_type": "author", "first_name": "Hisami", "last_name": "Yamanaka-Okumura", "name": null }, { "creator_type": "author", "first_name": "Akiyoshi", "last_name": "Hirayama", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Tatano", "name": null }, { "creator_type": "author", "first_name": "Keiko", "last_name": "Endo", "name": null }, { "creator_type": "author", "first_name": "Mayu", "last_name": "Honma", "name": null }, { "creator_type": "author", "first_name": "Kaori", "last_name": "Igarashi", "name": null }, { "creator_type": "author", "first_name": "Futaba", "last_name": "Shoji", "name": null }, { "creator_type": "author", "first_name": "Satsuki", "last_name": "Ikeda", "name": null }, { "creator_type": "author", "first_name": "Nozomi", "last_name": "Yamaguchi", "name": null }, { "creator_type": "author", "first_name": "Takafumi", "last_name": "Katayama", "name": null }, { "creator_type": "author", "first_name": "Yuji", "last_name": "Morine", "name": null }, { "creator_type": "author", "first_name": "Satoru", "last_name": "Imura", "name": null }, { "creator_type": "author", "first_name": "Tohru", "last_name": "Utsunomiya", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Masaru", "last_name": "Tomita", "name": null }, { "creator_type": "author", "first_name": "Mitsuo", "last_name": "Shimada", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.nut.2018.06.002" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "30391689" } }, "mesh": [ { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Carcinoma, Hepatocellular", "descriptor_ui": "D006528", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Hepatectomy", "descriptor_ui": "D006498", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Liver", "descriptor_ui": "D008099", "major_topic": false }, { "descriptor": "Liver Neoplasms", "descriptor_ui": "D008113", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Metabolome", "descriptor_ui": "D055442", "major_topic": true }, { "descriptor": "Perioperative Care", "descriptor_ui": "D019990", "major_topic": false }, { "descriptor": "Postoperative Complications", "descriptor_ui": "D011183", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019 Feb", "date_precision": "unknown", "issue": "", "normalized_date": null, "pages": "110-119", "proceedings_title": null, "publisher": "", "title": "Nutrition (Burbank, Los Angeles County, Calif.)", "volume": "58", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "Perioperative serum and urine metabolome analyses in patients with hepatocellular carcinoma undergoing partial hepatectomy.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "High fructose intake has been known to induce metabolic syndrome in laboratory animals and humans. Although fructose intake enhances sodium reabsorption and elevates blood pressure, role of fructose metabolism in this process has not been studied. Here we show that by ketohexokinase - the primary enzyme of fructose - is involved in regulation of renal sodium reabsorption and blood pressure via activation of the sodium hydrogen exchanger in renal proximal tubular cells. First, wild-type and ketohexokinase knockout mice (Male, C57BL/6) were fed fructose water or tap water with or without a high salt diet. Only wild type mice fed the combination of fructose water and high salt diet displayed increased systolic blood pressure and decreased urinary sodium excretion. In contrast, ketohexokinase knockout mice were protected. Second, urinary sodium excretion after intraperitoneal saline administration was reduced with the decreased phosphorylation of sodium hydrogen exchanger 3 in fructose-fed WT; these changes were not observed in the ketohexokinase knockout mice, however. Third, knockdown of ketohexokinase attenuated fructose-mediated increases of NHE activity with decreased cAMP levels in porcine renal proximal tubular cells (LLC-PK1). In conclusion, fructose metabolism by ketohexokinase increases sodium hydrogen exchanger activity in renal proximal tubular cells via decreased intracellular cAMP level, resulting in increased renal sodium reabsorption and blood pressure in mice.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Takahiro", "last_name": "Hayasaki", "name": null }, { "creator_type": "author", "first_name": "Takuji", "last_name": "Ishimoto", "name": null }, { "creator_type": "author", "first_name": "Tomohito", "last_name": "Doke", "name": null }, { "creator_type": "author", "first_name": "Akiyoshi", "last_name": "Hirayama", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Kazuhiro", "last_name": "Furuhashi", "name": null }, { "creator_type": "author", "first_name": "Noritoshi", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Tomoki", "last_name": "Kosugi", "name": null }, { "creator_type": "author", "first_name": "Naotake", "last_name": "Tsuboi", "name": null }, { "creator_type": "author", "first_name": "Miguel A.", "last_name": "Lanaspa", "name": null }, { "creator_type": "author", "first_name": "Richard J.", "last_name": "Johnson", "name": null }, { "creator_type": "author", "first_name": "Shoichi", "last_name": "Maruyama", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Kadomatsu", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.jnutbio.2019.05.017" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "31276916" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Blood Pressure", "descriptor_ui": "D001794", "major_topic": false }, { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "Fructokinases", "descriptor_ui": "D005631", "major_topic": false }, { "descriptor": "Fructose", "descriptor_ui": "D005632", "major_topic": false }, { "descriptor": "Kidney Tubules, Proximal", "descriptor_ui": "D007687", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Sodium", "descriptor_ui": "D012964", "major_topic": false }, { "descriptor": "Sodium-Hydrogen Exchanger 3", "descriptor_ui": "D000074083", "major_topic": false }, { "descriptor": "Swine", "descriptor_ui": "D013552", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019 Sep", "date_precision": "unknown", "issue": "", "normalized_date": null, "pages": "54-62", "proceedings_title": null, "publisher": "", "title": "The Journal of nutritional biochemistry", "volume": "71", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "Fructose increases the activity of sodium hydrogen exchanger in renal proximal tubules that is dependent on ketohexokinase.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Medullary thyroid carcinoma (MTC) develops from hyperplasia of thyroid C cells and represents one of the major causes of thyroid cancer mortality. Mutations in the cysteine-rich domain (CRD) of the RET gene are the most prevalent genetic cause of MTC. The current consensus holds that such cysteine mutations cause ligand-independent dimerization and constitutive activation of RET. However, given the number of the CRD mutations left uncharacterized, our understanding of the pathogenetic mechanisms by which CRD mutations lead to MTC remains incomplete. We report here that RET(C618F), a mutation identified in MTC patients, displays moderately high basal activity and requires the ligand for its full activation. To assess the biological significance of RET(C618F) in organogenesis, we generated a knock-in mouse line conditionally expressing RET(C618F) cDNA by the Ret promoter. The RET(C618F) allele can be made to be Ret-null and express mCherry by Cre-loxP recombination, which allows the assessment of the biological influence of RET(C618F) in vivo. Mice expressing RET(C618F) display mild C cell hyperplasia and increased numbers of enteric neurons, indicating that RET(C618F) confers gain-of-function phenotypes. This mouse line serves as a novel biological platform for investigating pathogenetic mechanisms involved in MTC and enteric hyperganglionosis.", "classifications": [ { "id": "Enomoto", "label": "Group Enomoto", "parent": "Enomoto", "type": "group" }, { "id": "Enomoto", "label": "Team Enomoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Mitsumasa", "last_name": "Okamoto", "name": null }, { "creator_type": "author", "first_name": "Yuta", "last_name": "Yoshioka", "name": null }, { "creator_type": "author", "first_name": "Kosaku", "last_name": "Maeda", "name": null }, { "creator_type": "author", "first_name": "Yuko", "last_name": "Bito", "name": null }, { "creator_type": "author", "first_name": "Takumi", "last_name": "Fukumoto", "name": null }, { "creator_type": "author", "first_name": "Toshihiro", "last_name": "Uesaka", "name": null }, { "creator_type": "author", "first_name": "Hideki", "last_name": "Enomoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/dvg.23292" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "30884088" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Carcinoma, Neuroendocrine", "descriptor_ui": "D018278", "major_topic": false }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Enteric Nervous System", "descriptor_ui": "D017615", "major_topic": false }, { "descriptor": "Gene Knock-In Techniques", "descriptor_ui": "D055879", "major_topic": false }, { "descriptor": "Germ-Line Mutation", "descriptor_ui": "D018095", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Hyperplasia", "descriptor_ui": "D006965", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Transgenic", "descriptor_ui": "D008822", "major_topic": false }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": false }, { "descriptor": "Nervous System Diseases", "descriptor_ui": "D009422", "major_topic": false }, { "descriptor": "Proto-Oncogene Proteins c-ret", "descriptor_ui": "D051096", "major_topic": false }, { "descriptor": "Thymus Hyperplasia", "descriptor_ui": "D013952", "major_topic": false }, { "descriptor": "Thyroid Gland", "descriptor_ui": "D013961", "major_topic": false }, { "descriptor": "Thyroid Neoplasms", "descriptor_ui": "D013964", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019 May", "date_precision": "unknown", "issue": "5", "normalized_date": null, "pages": "e23292", "proceedings_title": null, "publisher": "", "title": "Genesis (New York, N.Y. : 2000)", "volume": "57", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "Mice conditionally expressing RET(C618F) mutation display C cell hyperplasia and hyperganglionosis of the enteric nervous system.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "", "classifications": [ { "id": "Nishikii", "label": "Group Nishikii", "parent": "Shintaku", "type": "group" }, { "id": "Shintaku", "label": "Team Shintaku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Kenichi", "last_name": "Makishima", "name": null }, { "creator_type": "author", "first_name": "Naoshi", "last_name": "Obara", "name": null }, { "creator_type": "author", "first_name": "Kantaro", "last_name": "Ishitsuka", "name": null }, { "creator_type": "author", "first_name": "Shinichiro", "last_name": "Sukegawa", "name": null }, { "creator_type": "author", "first_name": "Sakurako", "last_name": "Suma", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Kiyoki", "name": null }, { "creator_type": "author", "first_name": "Naoko", "last_name": "Baba", "name": null }, { "creator_type": "author", "first_name": "Tatsuhiro", "last_name": "Sakamoto", "name": null }, { "creator_type": "author", "first_name": "Takayasu", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Manabu", "last_name": "Kusakabe", "name": null }, { "creator_type": "author", "first_name": "Hidekazu", "last_name": "Nishikii", "name": null }, { "creator_type": "author", "first_name": "Naoki", "last_name": "Kurita", "name": null }, { "creator_type": "author", "first_name": "Yasuhisa", "last_name": "Yokoyama", "name": null }, { "creator_type": "author", "first_name": "Mamiko", "last_name": "Sakata-Yanagimoto", "name": null }, { "creator_type": "author", "first_name": "Yuichi", "last_name": "Hasegawa", "name": null }, { "creator_type": "author", "first_name": "Shigeru", "last_name": "Chiba", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/s00277-018-3521-4" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "30324459" } }, "mesh": [ { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Anemia, Hemolytic, Autoimmune", "descriptor_ui": "D000744", "major_topic": false }, { "descriptor": "Antibodies, Monoclonal, Humanized", "descriptor_ui": "D061067", "major_topic": false }, { "descriptor": "Erythrocyte Transfusion", "descriptor_ui": "D017707", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019 Apr", "date_precision": "unknown", "issue": "4", "normalized_date": null, "pages": "1031-1032", "proceedings_title": null, "publisher": "", "title": "Annals of hematology", "volume": "98", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "High efficacy of eculizumab treatment for fulminant hemolytic anemia in primary cold agglutinin disease.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Direct in vivo reprogramming of cardiac fibroblasts into myocytes is an attractive therapeutic intervention in resolving myogenic deterioration. Current transgene-dependent approaches can restore cardiac function, but dependence on retroviral delivery and persistent retention of transgenic sequences are significant therapeutic hurdles. Chemical reprogramming has been established as a legitimate method to generate functional cell types, including those of the cardiac lineage. Here, we have extended this approach to generate progenitor cells that can differentiate into endothelial cells and cardiomyocytes using a single inhibitor protocol. Depletion of terminally differentiated cells and enrichment for proliferative cells result in a second expandable progenitor population that can robustly give rise to myofibroblasts and smooth muscle. Deployment of a genome-wide knockout screen with clustered regularly interspaced short palindromic repeats-guide RNA library to identify novel mediators that regulate the reprogramming revealed the involvement of DNA methyltransferase 1-associated protein 1 (Dmap1). Loss of Dmap1 reduced promoter methylation, increased the expression of Nkx2-5, and enhanced the retention of self-renewal, although further differentiation is inhibited because of the sustained expression of Cdh1. Our results hence establish Dmap1 as a modulator of cardiac reprogramming and myocytic induction. Stem Cells 2019;37:958-972.", "classifications": [ { "id": "Yusa", "label": "Group Yusa", "parent": "Eiraku", "type": "group" }, { "id": "Eiraku", "label": "Team Eiraku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Jason S. L.", "last_name": "Yu", "name": null }, { "creator_type": "author", "first_name": "Giorgia", "last_name": "Palano", "name": null }, { "creator_type": "author", "first_name": "Cindy", "last_name": "Lim", "name": null }, { "creator_type": "author", "first_name": "Aldo", "last_name": "Moggio", "name": null }, { "creator_type": "author", "first_name": "Lauren", "last_name": "Drowley", "name": null }, { "creator_type": "author", "first_name": "Alleyn T.", "last_name": "Plowright", "name": null }, { "creator_type": "author", "first_name": "Mohammad", "last_name": "Bohlooly-Y", "name": null }, { "creator_type": "author", "first_name": "Barry S.", "last_name": "Rosen", "name": null }, { "creator_type": "author", "first_name": "Emil M.", "last_name": "Hansson", "name": null }, { "creator_type": "author", "first_name": "Qing-Dong", "last_name": "Wang", "name": null }, { "creator_type": "author", "first_name": "Kosuke", "last_name": "Yusa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/stem.3012" }, "pmcid": { "normalized": "PMC6767549" }, "pmid": { "normalized": "30932271" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Benzamides", "descriptor_ui": "D001549", "major_topic": false }, { "descriptor": "Cadherins", "descriptor_ui": "D015820", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Cell Proliferation", "descriptor_ui": "D049109", "major_topic": false }, { "descriptor": "Cellular Reprogramming", "descriptor_ui": "D065150", "major_topic": false }, { "descriptor": "CRISPR-Cas Systems", "descriptor_ui": "D064113", "major_topic": true }, { "descriptor": "Dioxoles", "descriptor_ui": "D004149", "major_topic": false }, { "descriptor": "Fibroblasts", "descriptor_ui": "D005347", "major_topic": false }, { "descriptor": "Gene Editing", "descriptor_ui": "D000072669", "major_topic": false }, { "descriptor": "Homeobox Protein Nkx-2.5", "descriptor_ui": "D000072576", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Muscle, Smooth", "descriptor_ui": "D009130", "major_topic": false }, { "descriptor": "Myocardium", "descriptor_ui": "D009206", "major_topic": false }, { "descriptor": "Myocytes, Cardiac", "descriptor_ui": "D032383", "major_topic": false }, { "descriptor": "Primary Cell Culture", "descriptor_ui": "D061251", "major_topic": false }, { "descriptor": "Pyrazoles", "descriptor_ui": "D011720", "major_topic": false }, { "descriptor": "Pyridines", "descriptor_ui": "D011725", "major_topic": false }, { "descriptor": "Repressor Proteins", "descriptor_ui": "D012097", "major_topic": false }, { "descriptor": "RNA, Guide, CRISPR-Cas Systems", "descriptor_ui": "D000094704", "major_topic": false }, { "descriptor": "Stem Cells", "descriptor_ui": "D013234", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019 Jul", "date_precision": "unknown", "issue": "7", "normalized_date": null, "pages": "958-972", "proceedings_title": null, "publisher": "", "title": "Stem cells (Dayton, Ohio)", "volume": "37", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "CRISPR-Knockout Screen Identifies Dmap1 as a Regulator of Chemically Induced Reprogramming and Differentiation of Cardiac Progenitors.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Fatty acid (FA) oxidation is impaired and glycolysis is promoted in the damaged heart. However, the factor(s) in the early stages of myocardial metabolic impairment remain(s) unclear. C57B6 mice were subcutaneously administered monocrotaline (MCT) in doses of 0.3 mg/g body weight twice a week for 3 or 6 weeks. Right and left ventricles at 3 and 6 weeks after administration were subjected to capillary electrophoresis-mass spectrometry metabolomic analysis. We also examined mRNA and protein levels of key metabolic molecules. Although no evidence of PH and right ventricular failure was found in the MCT-administered mice by echocardiographic and histological analyzes, the expression levels of stress markers such as TNFalpha and IL-6 were increased in right and left ventricles even at 3 weeks, suggesting that there was myocardial damage. Metabolites in the tricarboxylic acid (TCA) cycle were decreased and those in glycolysis were increased at 6 weeks. The expression levels of FA oxidation-related factors were decreased at 6 weeks. The phosphorylation level of pyruvate dehydrogenase (PDH) was significantly decreased at 3 weeks. FA oxidation and the TCA cycle were down-regulated, whereas glycolysis was partially up-regulated by MCT-induced myocardial damage. PDH activation preceded these alterations, suggesting that PDH activation is one of the earliest events to compensate for a subtle metabolic impairment from myocardial damage.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Gaku", "last_name": "Nakai", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Shimura", "name": null }, { "creator_type": "author", "first_name": "Ken", "last_name": "Uesugi", "name": null }, { "creator_type": "author", "first_name": "Ichige", "last_name": "Kajimura", "name": null }, { "creator_type": "author", "first_name": "Qibin", "last_name": "Jiao", "name": null }, { "creator_type": "author", "first_name": "Yoichiro", "last_name": "Kusakari", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Nobuhito", "last_name": "Goda", "name": null }, { "creator_type": "author", "first_name": "Susumu", "last_name": "Minamisawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/s00380-018-1293-3" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "30386918" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Blotting, Western", "descriptor_ui": "D015153", "major_topic": false }, { "descriptor": "Cardiomyopathies", "descriptor_ui": "D009202", "major_topic": false }, { "descriptor": "Disease Models, Animal", "descriptor_ui": "D004195", "major_topic": false }, { "descriptor": "Down-Regulation", "descriptor_ui": "D015536", "major_topic": true }, { "descriptor": "Fatty Acids", "descriptor_ui": "D005227", "major_topic": false }, { "descriptor": "Heart Ventricles", "descriptor_ui": "D006352", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Monocrotaline", "descriptor_ui": "D016686", "major_topic": false }, { "descriptor": "Myocardium", "descriptor_ui": "D009206", "major_topic": false }, { "descriptor": "Oxidation-Reduction", "descriptor_ui": "D010084", "major_topic": false }, { "descriptor": "Pyruvate Dehydrogenase Complex", "descriptor_ui": "D011768", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019 Mar", "date_precision": "unknown", "issue": "3", "normalized_date": null, "pages": "545-555", "proceedings_title": null, "publisher": "", "title": "Heart and vessels", "volume": "34", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "Pyruvate dehydrogenase activation precedes the down-regulation of fatty acid oxidation in monocrotaline-induced myocardial toxicity in mice.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: We have previously reported that xeno-transplanted human ESC-derived retinas are able to mature in the immunodeficient retinal degeneration rodent models, similar to allo-transplantations using mouse iPSC-derived retina. The photoreceptors in the latter developed outer segments and formed synapses with host bipolar cells, driving light responses of host retinal ganglion cells. In view of clinical application, here we further confirmed the competency of human iPSC-derived retina (hiPSC-retina) to mature in the degenerated retinas of rat and monkey models. METHODS: Human iPSC-retinas were transplanted in rhodopsin mutant SD-Foxn1 Tg(S334ter)3LavRrrc nude rats and two monkeys with laser-induced photoreceptor degeneration. Graft maturation was studied by immunohistochemistry and its function was examined by multi-electrode array (MEA) recording in rat retinas and visually-guided saccade (VGS) in a monkey. FINDINGS: A substantial amount of mature photoreceptors in hiPSC-retina graft survived well in the host retinas for at least 5months (rat) to over 2years (monkey). In 4 of 7 transplanted rat retinas, RGC light responses were detected at the grafted area. A mild recovery of light perception was also suggested by the VGS performance 1.5years after transplantation in that monkey. INTERPRETATION: Our results support the competency of hiPSC-derived retinas to be clinically applied for transplantation therapy in retinal degeneration, although the light responses observed in the present models were not conclusively distinguishable from residual functions of degenerating host retinas. The functional analysis may be further elaborated using other models with more advanced retinal degeneration.", "classifications": [ { "id": "Eiraku", "label": "Group Eiraku", "parent": "Eiraku", "type": "group" }, { "id": "Eiraku", "label": "Team Eiraku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Hung-Ya", "last_name": "Tu", "name": null }, { "creator_type": "author", "first_name": "Takehito", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Shirai", "name": null }, { "creator_type": "author", "first_name": "Suguru", "last_name": "Yamasaki", "name": null }, { "creator_type": "author", "first_name": "Masaharu", "last_name": "Kinoshita", "name": null }, { "creator_type": "author", "first_name": "Keizo", "last_name": "Matsushita", "name": null }, { "creator_type": "author", "first_name": "Tomoyo", "last_name": "Hashiguchi", "name": null }, { "creator_type": "author", "first_name": "Hirotaka", "last_name": "Onoe", "name": null }, { "creator_type": "author", "first_name": "Take", "last_name": "Matsuyama", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Kuwahara", "name": null }, { "creator_type": "author", "first_name": "Akiyoshi", "last_name": "Kishino", "name": null }, { "creator_type": "author", "first_name": "Toru", "last_name": "Kimura", "name": null }, { "creator_type": "author", "first_name": "Mototsugu", "last_name": "Eiraku", "name": null }, { "creator_type": "author", "first_name": "Kiyoshi", "last_name": "Suzuma", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Kitaoka", "name": null }, { "creator_type": "author", "first_name": "Masayo", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Michiko", "last_name": "Mandai", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.ebiom.2018.11.028" }, "pmcid": { "normalized": "PMC6354559" }, "pmid": { "normalized": "30502055" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Disease Models, Animal", "descriptor_ui": "D004195", "major_topic": false }, { "descriptor": "Electroretinography", "descriptor_ui": "D004596", "major_topic": false }, { "descriptor": "Forkhead Transcription Factors", "descriptor_ui": "D051858", "major_topic": false }, { "descriptor": "Haplorhini", "descriptor_ui": "D000882", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Induced Pluripotent Stem Cells", "descriptor_ui": "D057026", "major_topic": false }, { "descriptor": "Lasers", "descriptor_ui": "D007834", "major_topic": false }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Rats, Nude", "descriptor_ui": "D011923", "major_topic": false }, { "descriptor": "Retina", "descriptor_ui": "D012160", "major_topic": false }, { "descriptor": "Retinal Degeneration", "descriptor_ui": "D012162", "major_topic": false }, { "descriptor": "Rhodopsin", "descriptor_ui": "D012243", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019 Jan", "date_precision": "unknown", "issue": "", "normalized_date": null, "pages": "562-574", "proceedings_title": null, "publisher": "", "title": "EBioMedicine", "volume": "39", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "Medium- to long-term survival and functional examination of human iPSC-derived retinas in rat and primate models of retinal degeneration.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Glucocorticoids have various medical uses but are accompanied by side effects. The glucocorticoid receptor (GR) has been reported to regulate the clock genes, but the underlying mechanisms are incompletely understood. In this study, we focused on the suppressive effect of the GR on the expression of Rev-erbalpha (Nr1d1), an important component of the clock regulatory circuits. Here we show that the GR suppresses Rev-erbalpha expression via the formation of a complex with CLOCK and BMAL1, which binds to the E-boxes in the Nr1d1 promoter. In this GR-CLOCK-BMAL1 complex, the GR does not directly bind to DNA, which is referred to as tethering. These findings provide new insights into the role of the GR in the control of circadian rhythm.", "classifications": [ { "id": "Miyamoto", "label": "Group Miyamoto", "parent": "Wakamoto", "type": "group" }, { "id": "Wakamoto", "label": "Team Wakamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yuki", "last_name": "Murayama", "name": null }, { "creator_type": "author", "first_name": "Naoya", "last_name": "Yahagi", "name": null }, { "creator_type": "author", "first_name": "Yoshinori", "last_name": "Takeuchi", "name": null }, { "creator_type": "author", "first_name": "Yuichi", "last_name": "Aita", "name": null }, { "creator_type": "author", "first_name": "Zahra", "last_name": "Mehrazad Saber", "name": null }, { "creator_type": "author", "first_name": "Nobuhiro", "last_name": "Wada", "name": null }, { "creator_type": "author", "first_name": "EnXu", "last_name": "Li", "name": null }, { "creator_type": "author", "first_name": "Xianying", "last_name": "Piao", "name": null }, { "creator_type": "author", "first_name": "Yoshikazu", "last_name": "Sawada", "name": null }, { "creator_type": "author", "first_name": "Akito", "last_name": "Shikama", "name": null }, { "creator_type": "author", "first_name": "Yukari", "last_name": "Masuda", "name": null }, { "creator_type": "author", "first_name": "Makiko", "last_name": "Nishi-Tatsumi", "name": null }, { "creator_type": "author", "first_name": "Midori", "last_name": "Kubota", "name": null }, { "creator_type": "author", "first_name": "Yoshihiko", "last_name": "Izumida", "name": null }, { "creator_type": "author", "first_name": "Takafumi", "last_name": "Miyamoto", "name": null }, { "creator_type": "author", "first_name": "Motohiro", "last_name": "Sekiya", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Matsuzaka", "name": null }, { "creator_type": "author", "first_name": "Yoshimi", "last_name": "Nakagawa", "name": null }, { "creator_type": "author", "first_name": "Yoko", "last_name": "Sugano", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Iwasaki", "name": null }, { "creator_type": "author", "first_name": "Kazuto", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Shigeru", "last_name": "Yatoh", "name": null }, { "creator_type": "author", "first_name": "Hiroaki", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Hiroaki", "last_name": "Yagyu", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Kawakami", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Shimano", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/1873-3468.13328" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "30659595" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "ARNTL Transcription Factors", "descriptor_ui": "D056930", "major_topic": false }, { "descriptor": "Circadian Rhythm", "descriptor_ui": "D002940", "major_topic": false }, { "descriptor": "CLOCK Proteins", "descriptor_ui": "D056926", "major_topic": false }, { "descriptor": "Dexamethasone", "descriptor_ui": "D003907", "major_topic": false }, { "descriptor": "Gene Expression Regulation", "descriptor_ui": "D005786", "major_topic": false }, { "descriptor": "HEK293 Cells", "descriptor_ui": "D057809", "major_topic": false }, { "descriptor": "Hep G2 Cells", "descriptor_ui": "D056945", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Nuclear Receptor Subfamily 1, Group D, Member 1", "descriptor_ui": "D056953", "major_topic": false }, { "descriptor": "Promoter Regions, Genetic", "descriptor_ui": "D011401", "major_topic": false }, { "descriptor": "Receptors, Glucocorticoid", "descriptor_ui": "D011965", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019 Feb", "date_precision": "unknown", "issue": "4", "normalized_date": null, "pages": "423-432", "proceedings_title": null, "publisher": "", "title": "FEBS letters", "volume": "593", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "Glucocorticoid receptor suppresses gene expression of Rev-erbalpha (Nr1d1) through interaction with the CLOCK complex.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "We construct a pathwise formulation for a multitype age-structured population dynamics, which involves an age-dependent cell replication and transition of gene- or phenotypes. By employing the formulation, we derive a variational representation of the stationary population growth rate; the representation comprises a tradeoff relation between growth effects and a single-cell intrinsic dynamics described by a semi-Markov process. This variational representation leads to a response relation of the stationary population growth rate, in which statistics on a retrospective history work as the response coefficients. These results contribute to predicting and controlling growing populations based on experimentally observed cell-lineage information.", "classifications": [ { "id": "Kobayashi", "label": "Group Kobayashi", "parent": "Wakamoto", "type": "group" }, { "id": "Wakamoto", "label": "Team Wakamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yuki", "last_name": "Sughiyama", "name": null }, { "creator_type": "author", "first_name": "So", "last_name": "Nakashima", "name": null }, { "creator_type": "author", "first_name": "Tetsuya J.", "last_name": "Kobayashi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1103/physreve.99.012413" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "30780204" } }, "mesh": [ { "descriptor": "Cell Death", "descriptor_ui": "D016923", "major_topic": false }, { "descriptor": "Models, Biological", "descriptor_ui": "D008954", "major_topic": true }, { "descriptor": "Phenotype", "descriptor_ui": "D010641", "major_topic": true }, { "descriptor": "Population Dynamics", "descriptor_ui": "D011157", "major_topic": true }, { "descriptor": "Single-Cell Analysis", "descriptor_ui": "D059010", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019 Jan", "date_precision": "unknown", "issue": "1-1", "normalized_date": null, "pages": "012413", "proceedings_title": null, "publisher": "", "title": "Physical review. E", "volume": "99", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "Fitness response relation of a multitype age-structured population dynamics.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: Enhancer of zeste homolog 2 (EZH2) is reported to be involved in lung cancer pathogenesis via the epigenetic regulation of various genes. Recently, EZH2 was shown to control mechanisms of adaptive resistance to immunotherapy in melanoma; however, the association between EZH2 and programmed death-ligand 1 (PD-L1), which reflects the tumor microenvironment, remains poorly understood. METHODS: A total of 428 patients with resected lung adenocarcinoma were analyzed for their EZH2 and PD-L1 expression by immunohistochemistry and evaluated to determine the association between the EZH2 and PD-L1 expression. RESULTS: Among 428 patients, the EZH2 expression was identified in 219 (51.2%) patients, while the PD-L1 expression was observed in 88 (20.6%) patients. The recurrence-free and overall survival were significantly shorter in patients with the EZH2 expression than in those without it. A multivariate analysis showed that EZH2 remained an independent prognosticator for recurrence-free and overall survival. Patients with the EZH2-positive lung adenocarcinoma exhibited a significantly higher expression of PD-L1 than did those without it. A logistic regression analysis with backward elimination revealed that the presence of lymphatic and vessel invasion and PD-L1 positivity were independently associated with the EZH2 expression, while age over 70 years, the presence of vessel invasion, wild-type epidermal growth factor receptor, and EZH2 positivity were significantly associated with the PD-L1 expression. CONCLUSIONS: EZH2-expressing lung adenocarcinomas were shown to express the PD-L1 protein more frequently than were nonexpressing lesions. This study provides the first evidence of a possible association between the EZH2 and PD-L1 expression in patients with resected lung adenocarcinoma.", "classifications": [ { "id": "Hamamoto", "label": "Group Hamamoto", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Gouji", "last_name": "Toyokawa", "name": null }, { "creator_type": "author", "first_name": "Kazuki", "last_name": "Takada", "name": null }, { "creator_type": "author", "first_name": "Tetsuzo", "last_name": "Tagawa", "name": null }, { "creator_type": "author", "first_name": "Ryuji", "last_name": "Hamamoto", "name": null }, { "creator_type": "author", "first_name": "Yuichi", "last_name": "Yamada", "name": null }, { "creator_type": "author", "first_name": "Mototsugu", "last_name": "Shimokawa", "name": null }, { "creator_type": "author", "first_name": "Yoshinao", "last_name": "Oda", "name": null }, { "creator_type": "author", "first_name": "Yoshihiko", "last_name": "Maehara", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.athoracsur.2018.08.056" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "30343006" } }, "mesh": [ { "descriptor": "Adenocarcinoma of Lung", "descriptor_ui": "D000077192", "major_topic": false }, { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Aged, 80 and over", "descriptor_ui": "D000369", "major_topic": false }, { "descriptor": "B7-H1 Antigen", "descriptor_ui": "D060890", "major_topic": false }, { "descriptor": "Biomarkers, Tumor", "descriptor_ui": "D014408", "major_topic": false }, { "descriptor": "Enhancer of Zeste Homolog 2 Protein", "descriptor_ui": "D000071221", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Gene Expression Regulation, Neoplastic", "descriptor_ui": "D015972", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Immunohistochemistry", "descriptor_ui": "D007150", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Neoplasm Staging", "descriptor_ui": "D009367", "major_topic": false }, { "descriptor": "Pneumonectomy", "descriptor_ui": "D011013", "major_topic": true }, { "descriptor": "Prognosis", "descriptor_ui": "D011379", "major_topic": false }, { "descriptor": "Retrospective Studies", "descriptor_ui": "D012189", "major_topic": false }, { "descriptor": "RNA, Neoplasm", "descriptor_ui": "D012334", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019 Feb", "date_precision": "unknown", "issue": "2", "normalized_date": null, "pages": "393-400", "proceedings_title": null, "publisher": "", "title": "The Annals of thoracic surgery", "volume": "107", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "A Positive Correlation Between the EZH2 and PD-L1 Expression in Resected Lung Adenocarcinomas.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Fascin, an actin-bundling protein, is present in the filopodia and lamellipodia of growth cones. However, few studies have examined lamellipodial fascin because it is difficult to observe. In this study, we evaluated lamellipodial fascin. We visualized the actin meshwork of lamellipodia in live growth cones by super-resolution microscopy. Fascin was colocalized with the actin meshwork in lamellipodia. Ser39 of fascin is a well-known phosphorylation site that controls the binding of fascin to actin filaments. Fluorescence recovery after photobleaching experiments with confocal microscopy showed that binding of fascin was controlled by phosphorylation of Ser39 in lamellipodia. Moreover, TPA, an agonist of protein kinase C, induced phosphorylation of fascin and dissociation from actin filaments in lamellipodia. Time series images showed that dissociation of fascin from the actin meshwork was induced by TPA. As fascin dissociated from actin filaments, the orientation of the actin filaments became parallel to the leading edge. The angle of actin filaments against the leading edge was changed from 73 degrees to 15 degrees . This decreased the elasticity of the lamellipodia by 40%, as measured by atomic force microscopy. These data suggest that actin bundles made by fascin contribute to elasticity of the growth cone.", "classifications": [ { "id": "Higaki", "label": "Group Higaki", "parent": "Ueda", "type": "group" }, { "id": "Ueda", "label": "Team Ueda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Minami", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Fujii", "name": null }, { "creator_type": "author", "first_name": "Kazumi", "last_name": "Hirano", "name": null }, { "creator_type": "author", "first_name": "Takumi", "last_name": "Higaki", "name": null }, { "creator_type": "author", "first_name": "Akira", "last_name": "Nagasaki", "name": null }, { "creator_type": "author", "first_name": "Ryoki", "last_name": "Ishikawa", "name": null }, { "creator_type": "author", "first_name": "Takaharu", "last_name": "Okajima", "name": null }, { "creator_type": "author", "first_name": "Kaoru", "last_name": "Katoh", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/gtc.12671" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "30664308" } }, "mesh": [ { "descriptor": "Actin Cytoskeleton", "descriptor_ui": "D008841", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Carrier Proteins", "descriptor_ui": "D002352", "major_topic": false }, { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "Elasticity", "descriptor_ui": "D004548", "major_topic": false }, { "descriptor": "Fluorescence Recovery After Photobleaching", "descriptor_ui": "D036681", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Microfilament Proteins", "descriptor_ui": "D008840", "major_topic": false }, { "descriptor": "Phosphorylation", "descriptor_ui": "D010766", "major_topic": false }, { "descriptor": "Pseudopodia", "descriptor_ui": "D011554", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019 Mar", "date_precision": "unknown", "issue": "3", "normalized_date": null, "pages": "202-213", "proceedings_title": null, "publisher": "", "title": "Genes to cells : devoted to molecular & cellular mechanisms", "volume": "24", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "Fascin in lamellipodia contributes to cell elasticity by controlling the orientation of filamentous actin.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND AND PURPOSE: Posttranslational modifications of cysteine residues represent a major aspect of redox biology, and their reliable detection is key in providing mechanistic insights. The metastable character of these modifications and cell lysis-induced artifactual oxidation render current state-of-the-art protocols to rely on alkylation-based stabilization of labile cysteine derivatives before cell/tissue rupture. An untested assumption in these procedures is that for all cysteine derivatives, alkylation rates are faster than their dynamic interchange. However, when the interconversion of cysteine derivatives is not rate limiting, electrophilic labelling is under Curtin-Hammett control; hence, the final alkylated mixture may not represent the speciation that prevailed before alkylation. EXPERIMENTAL APPROACH: Buffered aqueous solutions of inorganic, organic, cysteine, GSH and GAPDH polysulfide species were used. Additional experiments in human plasma and serum revealed that monobromobimane can extract sulfide from the endogenous sulfur pool by shifting speciation equilibria, suggesting caution should be exercised when interpreting experimental results using this tool. KEY RESULTS: In the majority of cases, the speciation of alkylated polysulfide/thiol derivatives depended on the experimental conditions. Alkylation perturbed sulfur speciation in both a concentration- and time-dependent manner and strong alkylating agents cleaved polysulfur chains. Moreover, the labelling of sulfenic acids with dimedone also affected cysteine speciation, suggesting that part of the endogenous pool of products previously believed to represent sulfenic acid species may represent polysulfides. CONCLUSIONS AND IMPLICATIONS: We highlight methodological caveats potentially arising from these pitfalls and conclude that current derivatization strategies often fail to adequately capture physiological speciation of sulfur species. LINKED ARTICLES: This article is part of a themed section on Chemical Biology of Reactive Sulfur Species. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v176.4/issuetoc.", "classifications": [ { "id": "Akaike", "label": "Group Akaike", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Virag", "last_name": "Bogdandi", "name": null }, { "creator_type": "author", "first_name": "Tomoaki", "last_name": "Ida", "name": null }, { "creator_type": "author", "first_name": "Thomas R.", "last_name": "Sutton", "name": null }, { "creator_type": "author", "first_name": "Christopher", "last_name": "Bianco", "name": null }, { "creator_type": "author", "first_name": "Tamas", "last_name": "Ditroi", "name": null }, { "creator_type": "author", "first_name": "Grielof", "last_name": "Koster", "name": null }, { "creator_type": "author", "first_name": "Hillary A.", "last_name": "Henthorn", "name": null }, { "creator_type": "author", "first_name": "Magda", "last_name": "Minnion", "name": null }, { "creator_type": "author", "first_name": "John P.", "last_name": "Toscano", "name": null }, { "creator_type": "author", "first_name": "Albert", "last_name": "van der Vliet", "name": null }, { "creator_type": "author", "first_name": "Michael D.", "last_name": "Pluth", "name": null }, { "creator_type": "author", "first_name": "Martin", "last_name": "Feelisch", "name": null }, { "creator_type": "author", "first_name": "Jon M.", "last_name": "Fukuto", "name": null }, { "creator_type": "author", "first_name": "Takaaki", "last_name": "Akaike", "name": null }, { "creator_type": "author", "first_name": "Peter", "last_name": "Nagy", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/bph.14394" }, "pmcid": { "normalized": "PMC6346080" }, "pmid": { "normalized": "29909607" } }, "mesh": [ { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Alkylating Agents", "descriptor_ui": "D000477", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Iodoacetamide", "descriptor_ui": "D007460", "major_topic": false }, { "descriptor": "Maleimides", "descriptor_ui": "D008301", "major_topic": false }, { "descriptor": "Methyl Methanesulfonate", "descriptor_ui": "D008741", "major_topic": false }, { "descriptor": "Sulfur Compounds", "descriptor_ui": "D013457", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019 Feb", "date_precision": "unknown", "issue": "4", "normalized_date": null, "pages": "646-670", "proceedings_title": null, "publisher": "", "title": "British journal of pharmacology", "volume": "176", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "Speciation of reactive sulfur species and their reactions with alkylating agents: do we have any clue about what is present inside the cell?", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "With an escalating number of predictive biomarkers emerging in non-small cell lung carcinoma (NSCLC), immunohistochemistry (IHC) is being used as a rapid and cost-effective tool for the screening and detection of many of these markers. In particular, robust IHC assays performed on formalin-fixed, paraffin-embedded (FFPE) tumor tissue are widely used as surrogate markers for ALK and ROS1 rearrangements and for detecting programmed death ligand 1 (PD-L1) expression in patients with advanced NSCLC; in addition, they have become essential for treatment decisions. Cytology samples represent the only source of tumor in a significant proportion of patients with inoperable NSCLC, and there is increasing demand for predictive biomarker testing on them. However, the wide variation in the types of cytology samples and their preparatory methods, the use of alcohol-based fixatives that interfere with immunochemistry results, the difficulty in procurement of cytology-specific controls, and the uncertainty regarding test validity have resulted in underutilization of cytology material for predictive immunocytochemistry (ICC), and most cytopathologists limit such testing to FFPE cell blocks (CBs). The purpose of this review is to: 1) analyze various preanalytical, analytical, and postanalytical factors influencing ICC results; 2) discuss measures for validation of ICC protocols; and 3) summarize published data on predictive ICC for ALK, ROS1, EGFR gene alterations and PD-L1 expression on lung cancer cytology. Based on our experience and from a review of the literature, we conclude that cytology specimens are in principal suitable for predictive ICC, but proper optimization and rigorous quality control for high-quality staining are essential, particularly for non-CB preparations.", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Deepali", "last_name": "Jain", "name": null }, { "creator_type": "author", "first_name": "Aruna", "last_name": "Nambirajan", "name": null }, { "creator_type": "author", "first_name": "Alain", "last_name": "Borczuk", "name": null }, { "creator_type": "author", "first_name": "Gang", "last_name": "Chen", "name": null }, { "creator_type": "author", "first_name": "Yuko", "last_name": "Minami", "name": null }, { "creator_type": "author", "first_name": "Andre L.", "last_name": "Moreira", "name": null }, { "creator_type": "author", "first_name": "Noriko", "last_name": "Motoi", "name": null }, { "creator_type": "author", "first_name": "Mauro", "last_name": "Papotti", "name": null }, { "creator_type": "author", "first_name": "Natasha", "last_name": "Rekhtman", "name": null }, { "creator_type": "author", "first_name": "Prudence A.", "last_name": "Russell", "name": null }, { "creator_type": "author", "first_name": "Spasenija", "last_name": "Savic Prince", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null }, { "creator_type": "author", "first_name": "Lukas", "last_name": "Bubendorf", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/cncy.22137" }, "pmcid": { "normalized": "PMC7493418" }, "pmid": { "normalized": "31050216" } }, "mesh": [ { "descriptor": "Biomarkers, Tumor", "descriptor_ui": "D014408", "major_topic": false }, { "descriptor": "Cytodiagnosis", "descriptor_ui": "D003581", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Immunohistochemistry", "descriptor_ui": "D007150", "major_topic": false }, { "descriptor": "Lung Neoplasms", "descriptor_ui": "D008175", "major_topic": false }, { "descriptor": "Predictive Value of Tests", "descriptor_ui": "D011237", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019 May", "date_precision": "unknown", "issue": "5", "normalized_date": null, "pages": "325-339", "proceedings_title": null, "publisher": "", "title": "Cancer cytopathology", "volume": "127", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "Immunocytochemistry for predictive biomarker testing in lung cancer cytology.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Epigenetic modifications, including histone modifications, stabilize cell-specific gene expression programmes to maintain cell identities in both metazoans and land plants(1-3). Notwithstanding the existence of these stable cell states, in land plants, stem cells are formed from differentiated cells during post-embryonic development and regeneration(4-6), indicating that land plants have an intrinsic ability to regulate epigenetic memory to initiate a new gene regulatory network. However, it is less well understood how epigenetic modifications are locally regulated to influence the specific genes necessary for cellular changes without affecting other genes in a genome. In this study, we found that ectopic induction of the AP2/ERF transcription factor STEMIN1 in leaf cells of the moss Physcomitrella patens decreases a repressive chromatin mark, histone H3 lysine 27 trimethylation (H3K27me3), on its direct target genes before cell division, resulting in the conversion of leaf cells to chloronema apical stem cells. STEMIN1 and its homologues positively regulate the formation of secondary chloronema apical stem cells from chloronema cells during development. Our results suggest that STEMIN1 functions within an intrinsic mechanism underlying local H3K27me3 reprogramming to initiate stem cell formation.", "classifications": [ { "id": "Sato", "label": "Group Sato", "parent": "Tsuchiya", "type": "group" }, { "id": "Tsuchiya", "label": "Team Tsuchiya", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Masaki", "last_name": "Ishikawa", "name": null }, { "creator_type": "author", "first_name": "Mio", "last_name": "Morishita", "name": null }, { "creator_type": "author", "first_name": "Yohei", "last_name": "Higuchi", "name": null }, { "creator_type": "author", "first_name": "Shunsuke", "last_name": "Ichikawa", "name": null }, { "creator_type": "author", "first_name": "Takaaki", "last_name": "Ishikawa", "name": null }, { "creator_type": "author", "first_name": "Tomoaki", "last_name": "Nishiyama", "name": null }, { "creator_type": "author", "first_name": "Yukiko", "last_name": "Kabeya", "name": null }, { "creator_type": "author", "first_name": "Yuji", "last_name": "Hiwatashi", "name": null }, { "creator_type": "author", "first_name": "Tetsuya", "last_name": "Kurata", "name": null }, { "creator_type": "author", "first_name": "Minoru", "last_name": "Kubo", "name": null }, { "creator_type": "author", "first_name": "Shuji", "last_name": "Shigenobu", "name": null }, { "creator_type": "author", "first_name": "Yosuke", "last_name": "Tamada", "name": null }, { "creator_type": "author", "first_name": "Yoshikatsu", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Mitsuyasu", "last_name": "Hasebe", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41477-019-0464-2" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "31285563" } }, "mesh": [ { "descriptor": "Bryopsida", "descriptor_ui": "D019068", "major_topic": false }, { "descriptor": "Cellular Reprogramming", "descriptor_ui": "D065150", "major_topic": false }, { "descriptor": "Epigenesis, Genetic", "descriptor_ui": "D044127", "major_topic": false }, { "descriptor": "Gene Expression Regulation, Plant", "descriptor_ui": "D018506", "major_topic": false }, { "descriptor": "Histones", "descriptor_ui": "D006657", "major_topic": false }, { "descriptor": "Methylation", "descriptor_ui": "D008745", "major_topic": false }, { "descriptor": "Plant Leaves", "descriptor_ui": "D018515", "major_topic": false }, { "descriptor": "Plant Proteins", "descriptor_ui": "D010940", "major_topic": false }, { "descriptor": "Stem Cells", "descriptor_ui": "D013234", "major_topic": false }, { "descriptor": "Transcription Factors", "descriptor_ui": "D014157", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019 Jul", "date_precision": "unknown", "issue": "7", "normalized_date": null, "pages": "681-690", "proceedings_title": null, "publisher": "", "title": "Nature plants", "volume": "5", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "Physcomitrella STEMIN transcription factor induces stem cell formation with epigenetic reprogramming.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Nestin-expressing stromal cells (NESCs) and Schwann cells in the bone marrow (BM) play crucial roles as a niche for normal hematopoietic stem cells in mice. It has been reported that both types of cells are decreased in myeloproliferative neoplasms in patients and also in a mouse model, whereas an increase in NESCs was reported in acute myeloid leukemia. It is thus of interest whether and how these BM stromal cells are structured in myelodysplastic syndromes (MDS). Here, we focused on NESCs and glial fibrillary acidic protein (GFAP)-expressing cells in the BM of MDS patients. We found a marked increase of NESCs in MDS with fibrosis (MDS-F) at a high frequency (9/19; 47.4%), but not in MDS without fibrosis (0/26; 0%). Intriguingly, in eight of the nine (88.9%) MDS-F cases with elevated NESCs, a majority of NESCs also expressed GFAP, with an additional increase in GFAP single-positive cells. Furthermore, in seven of them, we found a prominent structure characterized by neurofilament heavy chain staining surrounded by NESCs with GFAP expression. This structure may represent peripheral nerve axons surrounded by Schwann cells, and could be relevant to the pathophysiology of MDS-F.", "classifications": [ { "id": "Nishikii", "label": "Group Nishikii", "parent": "Shintaku", "type": "group" }, { "id": "Shintaku", "label": "Team Shintaku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Luan", "last_name": "Cao-Sy", "name": null }, { "creator_type": "author", "first_name": "Naoshi", "last_name": "Obara", "name": null }, { "creator_type": "author", "first_name": "Tatsuhiro", "last_name": "Sakamoto", "name": null }, { "creator_type": "author", "first_name": "Takayasu", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Keiichiro", "last_name": "Hattori", "name": null }, { "creator_type": "author", "first_name": "Shingo", "last_name": "Sakashita", "name": null }, { "creator_type": "author", "first_name": "Yasuhito", "last_name": "Nannya", "name": null }, { "creator_type": "author", "first_name": "Seishi", "last_name": "Ogawa", "name": null }, { "creator_type": "author", "first_name": "Hironori", "last_name": "Harada", "name": null }, { "creator_type": "author", "first_name": "Mamiko", "last_name": "Sakata-Yanagimoto", "name": null }, { "creator_type": "author", "first_name": "Hidekazu", "last_name": "Nishikii", "name": null }, { "creator_type": "author", "first_name": "Shigeru", "last_name": "Chiba", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/s12185-018-02576-9" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "30632058" } }, "mesh": [ { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Bone Marrow Cells", "descriptor_ui": "D001854", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Glial Fibrillary Acidic Protein", "descriptor_ui": "D005904", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Myelodysplastic Syndromes", "descriptor_ui": "D009190", "major_topic": false }, { "descriptor": "Nestin", "descriptor_ui": "D064231", "major_topic": false }, { "descriptor": "Primary Myelofibrosis", "descriptor_ui": "D055728", "major_topic": false }, { "descriptor": "Schwann Cells", "descriptor_ui": "D012583", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019 Mar", "date_precision": "unknown", "issue": "3", "normalized_date": null, "pages": "309-318", "proceedings_title": null, "publisher": "", "title": "International journal of hematology", "volume": "109", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "Prominence of nestin-expressing Schwann cells in bone marrow of patients with myelodysplastic syndromes with severe fibrosis.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Ming Sound", "last_name": "Tsao", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.jtho.2019.09.007" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "31757371" } }, "mesh": [ { "descriptor": "High-Throughput Nucleotide Sequencing", "descriptor_ui": "D059014", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Immunohistochemistry", "descriptor_ui": "D007150", "major_topic": false }, { "descriptor": "Lung Neoplasms", "descriptor_ui": "D008175", "major_topic": true }, { "descriptor": "Military Personnel", "descriptor_ui": "D008889", "major_topic": true }, { "descriptor": "Protein-Tyrosine Kinases", "descriptor_ui": "D011505", "major_topic": false }, { "descriptor": "Proto-Oncogene Proteins", "descriptor_ui": "D011518", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019 Dec", "date_precision": "unknown", "issue": "12", "normalized_date": null, "pages": "2035-2038", "proceedings_title": null, "publisher": "", "title": "Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer", "volume": "14", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "Old Soldiers Never Die: Is There Still a Role for Immunohistochemistry in the Era of Next-Generation Sequencing Panel Testing?", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Background:: Transcription factor Nrf2 (nuclear factor-erythroid 2-related factor 2) plays a key role in detoxification of electrophiles via formation of glutathione (GSH) adducts and subsequent excretion into extracellular spaces. We found that reactive sulfur species (RSS), such as cysteine persulfides produced by cystathionine γ-lyase (CSE), capture environmental electrophiles through formation of sulfur adducts. However, contributions of Nrf2 and CSE to the blockage of environmental electrophile-mediated toxicity remain to be evaluated. Objectives:: The aim of this study was to clarify roles that CSE and Nrf2 play in the protection against various environmental electrophiles. We also wished to clarify the molecular basis of the developmental window of toxicity through investigating expression levels of Nrf2, RSS-producing enzymes, and sulfur nucleophiles during developmental stages of mice. Methods:: Wild-type (WT), CSE knockout (KO), Nrf2 KO, Nrf2/CSE double KO (DKO) mice, and their primary hepatocytes were analyzed in this study. Cadmium (Cd), methylmercury (MeHg), 1,4-naphthoquinone, crotonaldehyde, and acrylamide were used. We conducted Western blotting, real-time polymerase chain reaction (PCR), 3-(4,5-dimethylthiazol-2-yl)-2,5-triphenyl tetrazolium bromide (MTT) assays, liquid chromatography–electrospray ionization–tandem mass spectrometry (LC-ESI-MS/MS) analysis, alanine transaminase (ALT) activity, histopathological analysis, and rotarod test. Results:: Primary hepatocytes from DKO mice were significantly more sensitive to the environmental electrophiles than each single KO counterpart. Both Nrf2 and CSE single KO mice were highly susceptible to Cd and MeHg, and such sensitivity was further exacerbated in the DKO mice. Lower-level expressions of CSE and sulfur nucleophiles than those in adult mice were observed in a window of developmental stage. Conclusions:: Our mouse model provided new insights into the response to environmental electrophiles; while Nrf2 is recognized as a key transcription factor for detoxification of environmental electrophiles, CSE is crucial factor to repress their toxicity in a parallel mode. In addition, the sensitivity of fetuses to MeHg appears to be, at least in part, associated with the restricted production of RSS due to low-level expression of CSE. https://doi.org/10.1289/EHP4949", "classifications": [ { "id": "Akaike", "label": "Group Akaike", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Masahiro", "last_name": "Akiyama", "name": null }, { "creator_type": "author", "first_name": "Takamitsu", "last_name": "Unoki", "name": null }, { "creator_type": "author", "first_name": "Yasuhiro", "last_name": "Shinkai", "name": null }, { "creator_type": "author", "first_name": "Isao", "last_name": "Ishii", "name": null }, { "creator_type": "author", "first_name": "Tomoaki", "last_name": "Ida", "name": null }, { "creator_type": "author", "first_name": "Takaaki", "last_name": "Akaike", "name": null }, { "creator_type": "author", "first_name": "Masayuki", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Yoshito", "last_name": "Kumagai", "name": null } ], "identifiers": { "doi": { "normalized": "10.1289/ehp4949" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "31166132" } }, "mesh": [ { "descriptor": "Acrylamide", "descriptor_ui": "D020106", "major_topic": false }, { "descriptor": "Aldehydes", "descriptor_ui": "D000447", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cadmium", "descriptor_ui": "D002104", "major_topic": false }, { "descriptor": "Cystathionine gamma-Lyase", "descriptor_ui": "D003542", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Gene Expression Regulation, Enzymologic", "descriptor_ui": "D015971", "major_topic": false }, { "descriptor": "Hepatocytes", "descriptor_ui": "D022781", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Methylmercury Compounds", "descriptor_ui": "D008767", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Naphthoquinones", "descriptor_ui": "D009285", "major_topic": false }, { "descriptor": "NF-E2-Related Factor 2", "descriptor_ui": "D051267", "major_topic": false }, { "descriptor": "Sulfides", "descriptor_ui": "D013440", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019 Jun", "date_precision": "unknown", "issue": "6", "normalized_date": null, "pages": "", "proceedings_title": null, "publisher": "", "title": "Environmental Health Perspectives", "volume": "127", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "Environmental Electrophile-Mediated Toxicity in Mice Lacking Nrf2, CSE, or Both.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The extracellular signal-regulated kinase (ERK) signaling pathway regulates a variety of biological processes including cell proliferation, survival, and differentiation. Since ERK activation promotes proliferation of many types of cells, its deregulated/constitutive activation is among general mechanisms for cancer. Recent advances in bioimaging techniques have enabled to visualize ERK activity in real-time at the single-cell level. Emerging evidence from such approaches suggests unexpectedly complex spatiotemporal dynamics of ERK activity in living cells and animals and their crucial roles in determining cellular responses. In this review, we discuss how ERK activity dynamics are regulated and how they affect biological processes including cell fate decisions, cell migration, embryonic development, tissue homeostasis, and tumorigenesis.", "classifications": [], "creators": [ { "creator_type": "author", "first_name": "Yu", "last_name": "Muta", "name": null }, { "creator_type": "author", "first_name": "Michiyuki", "last_name": "Matsuda", "name": null }, { "creator_type": "author", "first_name": "Masamichi", "last_name": "Imajo", "name": null } ], "identifiers": { "doi": { "normalized": "10.3390/cancers11040513" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "30974867" } }, "mesh": [], "publication": { "conference_name": null, "date": "2019 Apr", "date_precision": "unknown", "issue": "4", "normalized_date": null, "pages": "", "proceedings_title": null, "publisher": "", "title": "Cancers", "volume": "11", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "Divergent Dynamics and Functions of ERK MAP Kinase Signaling in Development, Homeostasis and Cancer: Lessons from Fluorescent Bioimaging.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Fluctuations in intracellular reactions (intrinsic noise) reduce the information transmitted from an extracellular input to a cellular response. However, recent studies have demonstrated that the decrease in the transmitted information with respect to extracellular input fluctuations (extrinsic noise) is smaller when the intrinsic noise is larger. Therefore, it has been suggested that robustness against extrinsic noise increases with the level of the intrinsic noise. We call this phenomenon intrinsic noise-induced robustness (INIR). As previous studies on this phenomenon have focused on complex biochemical reactions, the relation between INIR and the input-output of a system is unclear. Moreover, the mechanism of INIR remains elusive. In this paper, we address these questions by analyzing simple models. We first analyze a model in which the input-output relation is linear. We show that the robustness against extrinsic noise increases with the intrinsic noise, confirming the INIR phenomenon. Moreover, the robustness against the extrinsic noise is more strongly dependent on the intrinsic noise when the variance of the intrinsic noise is larger than that of the input distribution. Next, we analyze a threshold model in which the output depends on whether the input exceeds the threshold. When the threshold is equal to the mean of the input, INIR is realized, but when the threshold is much larger than the mean, the threshold model exhibits stochastic resonance, and INIR is not always apparent. The robustness against extrinsic noise and the transmitted information can be traded off against one another in the linear model and the threshold model without stochastic resonance, whereas they can be simultaneously increased in the threshold model with stochastic resonance.", "classifications": [ { "id": "Kuroda", "label": "Group Kuroda", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Takehiro", "last_name": "Tottori", "name": null }, { "creator_type": "author", "first_name": "Masashi", "last_name": "Fujii", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Kuroda", "name": null } ], "identifiers": { "doi": { "normalized": "10.1103/physreve.100.042403" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "31770940" } }, "mesh": [ { "descriptor": "Extracellular Space", "descriptor_ui": "D005110", "major_topic": false }, { "descriptor": "Intracellular Space", "descriptor_ui": "D042541", "major_topic": false }, { "descriptor": "Models, Biological", "descriptor_ui": "D008954", "major_topic": true }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": true } ], "publication": { "conference_name": null, "date": "2019 Oct", "date_precision": "unknown", "issue": "4-1", "normalized_date": null, "pages": "042403", "proceedings_title": null, "publisher": "", "title": "Physical review. E", "volume": "100", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "Robustness against additional noise in cellular information transmission.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "mTORC2 plays critical roles in metabolism, cell survival and actin cytoskeletal dynamics through the phosphorylation of AKT. Despite its importance to biology and medicine, it is unclear how mTORC2-mediated AKT phosphorylation is controlled. Here, we identify an unforeseen principle by which a GDP-bound form of the conserved small G protein Rho GTPase directly activates mTORC2 in AKT phosphorylation in social amoebae (Dictyostelium discoideum) cells. Using biochemical reconstitution with purified proteins, we demonstrate that Rho-GDP promotes AKT phosphorylation by assembling a supercomplex with Ras-GTP and mTORC2. This supercomplex formation is controlled by the chemoattractant-induced phosphorylation of Rho-GDP at S192 by GSK-3. Furthermore, Rho-GDP rescues defects in both mTORC2-mediated AKT phosphorylation and directed cell migration in Rho-null cells in a manner dependent on phosphorylation of S192. Thus, in contrast to the prevailing view that the GDP-bound forms of G proteins are inactive, our study reveals that mTORC2-AKT signalling is activated by Rho-GDP.", "classifications": [ { "id": "Sawai", "label": "Group Sawai", "parent": "Sawai", "type": "group" }, { "id": "Sawai", "label": "Team Sawai", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Senoo", "name": null }, { "creator_type": "author", "first_name": "Yoichiro", "last_name": "Kamimura", "name": null }, { "creator_type": "author", "first_name": "Reona", "last_name": "Kimura", "name": null }, { "creator_type": "author", "first_name": "Akihiko", "last_name": "Nakajima", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Sawai", "name": null }, { "creator_type": "author", "first_name": "Hiromi", "last_name": "Sesaki", "name": null }, { "creator_type": "author", "first_name": "Miho", "last_name": "Iijima", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41556-019-0348-8" }, "pmcid": { "normalized": "PMC6650273" }, "pmid": { "normalized": "31263268" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Movement", "descriptor_ui": "D002465", "major_topic": false }, { "descriptor": "Cytoskeleton", "descriptor_ui": "D003599", "major_topic": false }, { "descriptor": "Dimerization", "descriptor_ui": "D019281", "major_topic": true }, { "descriptor": "Glycogen Synthase Kinase 3", "descriptor_ui": "D038362", "major_topic": false }, { "descriptor": "GTP-Binding Proteins", "descriptor_ui": "D019204", "major_topic": false }, { "descriptor": "Guanosine Diphosphate", "descriptor_ui": "D006153", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mechanistic Target of Rapamycin Complex 2", "descriptor_ui": "D000076225", "major_topic": false }, { "descriptor": "Phosphorylation", "descriptor_ui": "D010766", "major_topic": false }, { "descriptor": "Proto-Oncogene Proteins c-akt", "descriptor_ui": "D051057", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019 Jul", "date_precision": "unknown", "issue": "7", "normalized_date": null, "pages": "867-878", "proceedings_title": null, "publisher": "", "title": "Nature cell biology", "volume": "21", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "Phosphorylated Rho-GDP directly activates mTORC2 kinase towards AKT through dimerization with Ras-GTP to regulate cell migration.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Since the 2015 WHO classification was introduced into clinical practice, immunohistochemistry (IHC) has figured prominently in lung cancer diagnosis. In addition to distinction of small cell versus non-small cell carcinoma, patients' treatment of choice is directly linked to histologic subtypes of non-small cell carcinoma, which pertains to IHC results, particularly for poorly differentiated tumors. The use of IHC has improved diagnostic accuracy in the classification of lung carcinoma, but the interpretation of IHC results remains challenging in some instances. Also, pathologists must be aware of many interpretation pitfalls, and the use of IHC should be efficient to spare the tissue for molecular testing. The International Association for the Study of Lung Cancer Pathology Committee received questions on practical application and interpretation of IHC in lung cancer diagnosis. After discussions in several International Association for the Study of Lung Cancer Pathology Committee meetings, the issues and caveats were summarized in terms of 11 key questions covering common and important diagnostic situations in a daily clinical practice with some relevant challenging queries. The questions cover topics such as the best IHC markers for distinguishing NSCLC subtypes, differences in thyroid transcription factor 1 clones, and the utility of IHC in diagnosing uncommon subtypes of lung cancer and distinguishing primary from metastatic tumors. This article provides answers and explanations for the key questions about the use of IHC in diagnosis of lung carcinoma, representing viewpoints of experts in thoracic pathology that should assist the community in the appropriate use of IHC in diagnostic pathology.", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null }, { "creator_type": "author", "first_name": "Sanja", "last_name": "Dacic", "name": null }, { "creator_type": "author", "first_name": "Alain C.", "last_name": "Borczuk", "name": null }, { "creator_type": "author", "first_name": "Arne", "last_name": "Warth", "name": null }, { "creator_type": "author", "first_name": "Prudence A.", "last_name": "Russell", "name": null }, { "creator_type": "author", "first_name": "Sylvie", "last_name": "Lantuejoul", "name": null }, { "creator_type": "author", "first_name": "Mary Beth", "last_name": "Beasley", "name": null }, { "creator_type": "author", "first_name": "Erik", "last_name": "Thunnissen", "name": null }, { "creator_type": "author", "first_name": "Giuseppe", "last_name": "Pelosi", "name": null }, { "creator_type": "author", "first_name": "Natasha", "last_name": "Rekhtman", "name": null }, { "creator_type": "author", "first_name": "Lukas", "last_name": "Bubendorf", "name": null }, { "creator_type": "author", "first_name": "Mari", "last_name": "Mino-Kenudson", "name": null }, { "creator_type": "author", "first_name": "Akihiko", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Kim R.", "last_name": "Geisinger", "name": null }, { "creator_type": "author", "first_name": "Masayuki", "last_name": "Noguchi", "name": null }, { "creator_type": "author", "first_name": "Lucian R.", "last_name": "Chirieac", "name": null }, { "creator_type": "author", "first_name": "Johan", "last_name": "Bolting", "name": null }, { "creator_type": "author", "first_name": "Jin-Haeng", "last_name": "Chung", "name": null }, { "creator_type": "author", "first_name": "Teh-Ying", "last_name": "Chou", "name": null }, { "creator_type": "author", "first_name": "Gang", "last_name": "Chen", "name": null }, { "creator_type": "author", "first_name": "Claudia", "last_name": "Poleri", "name": null }, { "creator_type": "author", "first_name": "Fernando", "last_name": "Lopez-Rios", "name": null }, { "creator_type": "author", "first_name": "Mauro", "last_name": "Papotti", "name": null }, { "creator_type": "author", "first_name": "Lynette M.", "last_name": "Sholl", "name": null }, { "creator_type": "author", "first_name": "Anja C.", "last_name": "Roden", "name": null }, { "creator_type": "author", "first_name": "William D.", "last_name": "Travis", "name": null }, { "creator_type": "author", "first_name": "Fred R.", "last_name": "Hirsch", "name": null }, { "creator_type": "author", "first_name": "Keith M.", "last_name": "Kerr", "name": null }, { "creator_type": "author", "first_name": "Ming-Sound", "last_name": "Tsao", "name": null }, { "creator_type": "author", "first_name": "Andrew G.", "last_name": "Nicholson", "name": null }, { "creator_type": "author", "first_name": "Ignacio", "last_name": "Wistuba", "name": null }, { "creator_type": "author", "first_name": "Andre L.", "last_name": "Moreira", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.jtho.2018.12.005" }, "pmcid": { "normalized": "PMC6422775" }, "pmid": { "normalized": "30572031" } }, "mesh": [ { "descriptor": "Antibodies, Monoclonal", "descriptor_ui": "D000911", "major_topic": false }, { "descriptor": "Biomarkers, Tumor", "descriptor_ui": "D014408", "major_topic": false }, { "descriptor": "Diagnosis, Differential", "descriptor_ui": "D003937", "major_topic": false }, { "descriptor": "Early Detection of Cancer", "descriptor_ui": "D055088", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Immunohistochemistry", "descriptor_ui": "D007150", "major_topic": false }, { "descriptor": "Lung Neoplasms", "descriptor_ui": "D008175", "major_topic": false }, { "descriptor": "Practice Guidelines as Topic", "descriptor_ui": "D017410", "major_topic": false }, { "descriptor": "Prognosis", "descriptor_ui": "D011379", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019 Mar", "date_precision": "unknown", "issue": "3", "normalized_date": null, "pages": "377-407", "proceedings_title": null, "publisher": "", "title": "Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer", "volume": "14", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "Best Practices Recommendations for Diagnostic Immunohistochemistry in Lung Cancer.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Hypoxia-inducible factor 1alpha is a key regulator of the hypoxia response in normal and cancer tissues. It is well recognized to regulate glycolysis and is a target for therapy. However, how tumor cells adapt to grow in the absence of HIF1alpha is poorly understood and an important concept to understand for developing targeted therapies is the flexibility of the metabolic response to hypoxia via alternative pathways. We analyzed pathways that allow cells to survive hypoxic stress in the absence of HIF1alpha, using the HCT116 colon cancer cell line with deleted HIF1alpha versus control. Spheroids were used to provide a 3D model of metabolic gradients. We conducted a metabolomic, transcriptomic, and proteomic analysis and integrated the results. These showed surprisingly that in three-dimensional growth, a key regulatory step of glycolysis is Aldolase A rather than phosphofructokinase. Furthermore, glucose uptake could be maintained in hypoxia through upregulation of GLUT14, not previously recognized in this role. Finally, there was a marked adaptation and change of phosphocreatine energy pathways, which made the cells susceptible to inhibition of creatine metabolism in hypoxic conditions. Overall, our studies show a complex adaptation to hypoxia that can bypass HIF1alpha, but it is targetable and it provides new insight into the key metabolic pathways involved in cancer growth. IMPLICATIONS: Under hypoxia and HIF1 blockade, cancer cells adapt their energy metabolism via upregulation of the GLUT14 glucose transporter and creatine metabolism providing new avenues for drug targeting.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Alessandro", "last_name": "Valli", "name": null }, { "creator_type": "author", "first_name": "Matteo", "last_name": "Morotti", "name": null }, { "creator_type": "author", "first_name": "Christos E.", "last_name": "Zois", "name": null }, { "creator_type": "author", "first_name": "Patrick K.", "last_name": "Albers", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Katharina", "last_name": "Feldinger", "name": null }, { "creator_type": "author", "first_name": "Roman", "last_name": "Fischer", "name": null }, { "creator_type": "author", "first_name": "Martin", "last_name": "Frejno", "name": null }, { "creator_type": "author", "first_name": "Alan", "last_name": "McIntyre", "name": null }, { "creator_type": "author", "first_name": "Esther", "last_name": "Bridges", "name": null }, { "creator_type": "author", "first_name": "Syed", "last_name": "Haider", "name": null }, { "creator_type": "author", "first_name": "Francesca M.", "last_name": "Buffa", "name": null }, { "creator_type": "author", "first_name": "Dilair", "last_name": "Baban", "name": null }, { "creator_type": "author", "first_name": "Miguel", "last_name": "Rodriguez", "name": null }, { "creator_type": "author", "first_name": "Oscar", "last_name": "Yanes", "name": null }, { "creator_type": "author", "first_name": "Hannah J.", "last_name": "Whittington", "name": null }, { "creator_type": "author", "first_name": "Hannah A.", "last_name": "Lake", "name": null }, { "creator_type": "author", "first_name": "Sevasti", "last_name": "Zervou", "name": null }, { "creator_type": "author", "first_name": "Craig A.", "last_name": "Lygate", "name": null }, { "creator_type": "author", "first_name": "Benedikt M.", "last_name": "Kessler", "name": null }, { "creator_type": "author", "first_name": "Adrian L.", "last_name": "Harris", "name": null } ], "identifiers": { "doi": { "normalized": "10.1158/1541-7786.mcr-18-0315" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "30885992" } }, "mesh": [ { "descriptor": "Colonic Neoplasms", "descriptor_ui": "D003110", "major_topic": false }, { "descriptor": "Creatine", "descriptor_ui": "D003401", "major_topic": false }, { "descriptor": "Energy Metabolism", "descriptor_ui": "D004734", "major_topic": false }, { "descriptor": "Fructose-Bisphosphate Aldolase", "descriptor_ui": "D005634", "major_topic": false }, { "descriptor": "Glucose", "descriptor_ui": "D005947", "major_topic": false }, { "descriptor": "Glucose Transport Proteins, Facilitative", "descriptor_ui": "D051246", "major_topic": false }, { "descriptor": "Glycolysis", "descriptor_ui": "D006019", "major_topic": false }, { "descriptor": "HCT116 Cells", "descriptor_ui": "D045325", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Hypoxia-Inducible Factor 1, alpha Subunit", "descriptor_ui": "D051795", "major_topic": false }, { "descriptor": "Spheroids, Cellular", "descriptor_ui": "D018874", "major_topic": false }, { "descriptor": "Tumor Hypoxia", "descriptor_ui": "D000072258", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019 Jul", "date_precision": "unknown", "issue": "7", "normalized_date": null, "pages": "1531-1544", "proceedings_title": null, "publisher": "", "title": "Molecular cancer research : MCR", "volume": "17", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "Adaptation to HIF1alpha Deletion in Hypoxic Cancer Cells by Upregulation of GLUT14 and Creatine Metabolism.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Cysteine persulfide and polysulfide are produced in cells and exist in abundance in both low MW and protein fractions. However, the mechanism of regulation of the formation of cellular cysteine polysulfides and the physiological functions of cysteine persulfides/polysulfides produced in cells are not fully understood. We recently demonstrated that cysteinyl-tRNA synthetase (CARS) is a novel cysteine persulfide synthase. CARS is involved in protein polysulfidation that is coupled with translation. In particular, mitochondria function in biogenesis and bioenergetics is also supported and up-regulated by cysteine persulfide derived from mitochondrial CARS (also known as CARS2). Here, we provide an overview of recent advances in reactive persulfide research and our understanding of the mechanisms underlying the formation and the physiological roles of reactive persufides, with a primary focus on the formation of cysteine persulfide by CARS and the most fundamental mitochondrial bioenergetics mediated by persulfides, that is, sulfur respiration. LINKED ARTICLES: This article is part of a themed section on Chemical Biology of Reactive Sulfur Species. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v176.4/issuetoc.", "classifications": [ { "id": "Akaike", "label": "Group Akaike", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Shigemoto", "last_name": "Fujii", "name": null }, { "creator_type": "author", "first_name": "Tomohiro", "last_name": "Sawa", "name": null }, { "creator_type": "author", "first_name": "Hozumi", "last_name": "Motohashi", "name": null }, { "creator_type": "author", "first_name": "Takaaki", "last_name": "Akaike", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/bph.14356" }, "pmcid": { "normalized": "PMC6346073" }, "pmid": { "normalized": "29748969" } }, "mesh": [ { "descriptor": "Amino Acyl-tRNA Synthetases", "descriptor_ui": "D000604", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cysteine", "descriptor_ui": "D003545", "major_topic": false }, { "descriptor": "Disulfides", "descriptor_ui": "D004220", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Sulfides", "descriptor_ui": "D013440", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019 Feb", "date_precision": "unknown", "issue": "4", "normalized_date": null, "pages": "607-615", "proceedings_title": null, "publisher": "", "title": "British journal of pharmacology", "volume": "176", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "Persulfide synthases that are functionally coupled with translation mediate sulfur respiration in mammalian cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The hypothalamus is a higher center of the autonomic nervous system and maintains essential body homeostasis including respiration. The paraventricular nucleus, perifornical area, dorsomedial hypothalamus, and lateral and posterior hypothalamus are the primary nuclei of the hypothalamus critically involved in respiratory control. These hypothalamic nuclei are interconnected with respiratory nuclei located in the midbrain, pons, medulla and spinal cord. We provide an extensive review of the role of the above hypothalamic nuclei in the maintenance of basal ventilation, and modulation of respiration in hypoxic and hypercapnic conditions, during dynamic exercise, in awake and sleep states, and under stress. Dysfunction of the hypothalamus causes abnormal breathing and hypoventilation. However, the cellular and molecular mechanisms how the hypothalamus integrates and modulates autonomic and respiratory functions remain to be elucidated.", "classifications": [ { "id": "Yokota", "label": "Group Yokota", "parent": "Enomoto", "type": "group" }, { "id": "Enomoto", "label": "Team Enomoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Isato", "last_name": "Fukushi", "name": null }, { "creator_type": "author", "first_name": "Shigefumi", "last_name": "Yokota", "name": null }, { "creator_type": "author", "first_name": "Yasumasa", "last_name": "Okada", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.resp.2018.07.003" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "30009993" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Exercise", "descriptor_ui": "D015444", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Hypercapnia", "descriptor_ui": "D006935", "major_topic": false }, { "descriptor": "Hypothalamus", "descriptor_ui": "D007031", "major_topic": false }, { "descriptor": "Hypoxia", "descriptor_ui": "D000860", "major_topic": false }, { "descriptor": "Nerve Net", "descriptor_ui": "D009415", "major_topic": false }, { "descriptor": "Respiration", "descriptor_ui": "D012119", "major_topic": true }, { "descriptor": "Respiratory Center", "descriptor_ui": "D012125", "major_topic": false }, { "descriptor": "Stress, Psychological", "descriptor_ui": "D013315", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019 Jul", "date_precision": "unknown", "issue": "", "normalized_date": null, "pages": "172-179", "proceedings_title": null, "publisher": "", "title": "Respiratory physiology & neurobiology", "volume": "265", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "The role of the hypothalamus in modulation of respiration.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: Ultrafiltration failure associated with peritoneal membrane dysfunction is one of the main complications for patients on long-term peritoneal dialysis (PD). The dialysate-to-plasma concentration ratio (D/P) of creatinine is widely used to assess peritoneal membrane function. However, other small-sized solutes have not been studied in detail as potential indicators of peritoneal permeability. METHODS: We studied the D/Ps of small, middle-sized and large molecules in peritoneal equilibration tests in 50 PD patients. We applied metabolomic analysis of comprehensive small molecular metabolites using capillary electrophoresis time-of-flight mass spectrometry. RESULTS: D/Ps of middle-sized and large molecules correlated positively with D/P creatinine. Most D/Ps of small molecules correlated positively with D/P creatinine. Among 38 small molecules contained in the dialysate, urea, citrulline and choline showed significantly lower ability to permeate than creatinine. In the relationship between D/Ps of creatinine and small molecules, regression coefficients of three molecules were less than 0.3, representing no correlation to D/P creatinine. Five molecules showed negative regression coefficients. Among these molecules, hippurate and 3-indoxyl sulfate showed relatively high teinpro binding rates, which may affect permeability. Serum concentrations of two molecules were higher in the Low Kt/V group, mainly due to high protein binding rates. CONCLUSIONS: D/Ps of some molecules did not correlate with D/P creatinine. Factors other than molecular weight, such as charge and protein binding rate, are involved in peritoneal transport rates. Metabolomic analysis appears useful to analyze small molecular uremic toxins, which could accumulate in PD patients, and the status of peritoneal membrane transport for each molecule.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Marina", "last_name": "Asano", "name": null }, { "creator_type": "author", "first_name": "Takako", "last_name": "Ishii", "name": null }, { "creator_type": "author", "first_name": "Akiyoshi", "last_name": "Hirayama", "name": null }, { "creator_type": "author", "first_name": "Masashi", "last_name": "Mizuno", "name": null }, { "creator_type": "author", "first_name": "Yasuhiro", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Fumiko", "last_name": "Sakata", "name": null }, { "creator_type": "author", "first_name": "Shin-Ichi", "last_name": "Akiyama", "name": null }, { "creator_type": "author", "first_name": "Shoichi", "last_name": "Maruyama", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Kinashi", "name": null }, { "creator_type": "author", "first_name": "Takayuki", "last_name": "Katsuno", "name": null }, { "creator_type": "author", "first_name": "Yasuhiko", "last_name": "Ito", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/s10157-018-1611-1" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "29968125" } }, "mesh": [ { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Biomarkers", "descriptor_ui": "D015415", "major_topic": false }, { "descriptor": "Creatinine", "descriptor_ui": "D003404", "major_topic": false }, { "descriptor": "Dialysis Solutions", "descriptor_ui": "D015314", "major_topic": false }, { "descriptor": "Electrophoresis, Capillary", "descriptor_ui": "D019075", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Kidney Failure, Chronic", "descriptor_ui": "D007676", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mass Spectrometry", "descriptor_ui": "D013058", "major_topic": false }, { "descriptor": "Metabolomics", "descriptor_ui": "D055432", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Molecular Weight", "descriptor_ui": "D008970", "major_topic": false }, { "descriptor": "Peritoneal Dialysis", "descriptor_ui": "D010530", "major_topic": true }, { "descriptor": "Peritoneum", "descriptor_ui": "D010537", "major_topic": false }, { "descriptor": "Permeability", "descriptor_ui": "D010539", "major_topic": false }, { "descriptor": "Protein Binding", "descriptor_ui": "D011485", "major_topic": false }, { "descriptor": "Ultrafiltration", "descriptor_ui": "D014462", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019 Jan", "date_precision": "unknown", "issue": "1", "normalized_date": null, "pages": "122-134", "proceedings_title": null, "publisher": "", "title": "Clinical and experimental nephrology", "volume": "23", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "Differences in peritoneal solute transport rates in peritoneal dialysis.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Branched-chain amino acid (BCAA; valine, leucine and isoleucine) supplementation is often beneficial to energy expenditure; however, increased circulating levels of BCAA are linked to obesity and diabetes. The mechanisms of this paradox remain unclear. Here we report that, on cold exposure, brown adipose tissue (BAT) actively utilizes BCAA in the mitochondria for thermogenesis and promotes systemic BCAA clearance in mice and humans. In turn, a BAT-specific defect in BCAA catabolism attenuates systemic BCAA clearance, BAT fuel oxidation and thermogenesis, leading to diet-induced obesity and glucose intolerance. Mechanistically, active BCAA catabolism in BAT is mediated by SLC25A44, which transports BCAAs into mitochondria. Our results suggest that BAT serves as a key metabolic filter that controls BCAA clearance via SLC25A44, thereby contributing to the improvement of metabolic health.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Takeshi", "last_name": "Yoneshiro", "name": null }, { "creator_type": "author", "first_name": "Qiang", "last_name": "Wang", "name": null }, { "creator_type": "author", "first_name": "Kazuki", "last_name": "Tajima", "name": null }, { "creator_type": "author", "first_name": "Mami", "last_name": "Matsushita", "name": null }, { "creator_type": "author", "first_name": "Hiroko", "last_name": "Maki", "name": null }, { "creator_type": "author", "first_name": "Kaori", "last_name": "Igarashi", "name": null }, { "creator_type": "author", "first_name": "Zhipeng", "last_name": "Dai", "name": null }, { "creator_type": "author", "first_name": "Phillip J.", "last_name": "White", "name": null }, { "creator_type": "author", "first_name": "Robert W.", "last_name": "McGarrah", "name": null }, { "creator_type": "author", "first_name": "Olga R.", "last_name": "Ilkayeva", "name": null }, { "creator_type": "author", "first_name": "Yann", "last_name": "Deleye", "name": null }, { "creator_type": "author", "first_name": "Yasuo", "last_name": "Oguri", "name": null }, { "creator_type": "author", "first_name": "Mito", "last_name": "Kuroda", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Ikeda", "name": null }, { "creator_type": "author", "first_name": "Huixia", "last_name": "Li", "name": null }, { "creator_type": "author", "first_name": "Ayano", "last_name": "Ueno", "name": null }, { "creator_type": "author", "first_name": "Maki", "last_name": "Ohishi", "name": null }, { "creator_type": "author", "first_name": "Takamasa", "last_name": "Ishikawa", "name": null }, { "creator_type": "author", "first_name": "Kyeongkyu", "last_name": "Kim", "name": null }, { "creator_type": "author", "first_name": "Yong", "last_name": "Chen", "name": null }, { "creator_type": "author", "first_name": "Carlos Henrique", "last_name": "Sponton", "name": null }, { "creator_type": "author", "first_name": "Rachana N.", "last_name": "Pradhan", "name": null }, { "creator_type": "author", "first_name": "Homa", "last_name": "Majd", "name": null }, { "creator_type": "author", "first_name": "Vanille Juliette", "last_name": "Greiner", "name": null }, { "creator_type": "author", "first_name": "Momoko", "last_name": "Yoneshiro", "name": null }, { "creator_type": "author", "first_name": "Zachary", "last_name": "Brown", "name": null }, { "creator_type": "author", "first_name": "Maria", "last_name": "Chondronikola", "name": null }, { "creator_type": "author", "first_name": "Haruya", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Tsuyoshi", "last_name": "Goto", "name": null }, { "creator_type": "author", "first_name": "Teruo", "last_name": "Kawada", "name": null }, { "creator_type": "author", "first_name": "Labros", "last_name": "Sidossis", "name": null }, { "creator_type": "author", "first_name": "Francis C.", "last_name": "Szoka", "name": null }, { "creator_type": "author", "first_name": "Michael T.", "last_name": "McManus", "name": null }, { "creator_type": "author", "first_name": "Masayuki", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Shingo", "last_name": "Kajimura", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41586-019-1503-x" }, "pmcid": { "normalized": "PMC6715529" }, "pmid": { "normalized": "31435015" } }, "mesh": [ { "descriptor": "Adipose Tissue, Brown", "descriptor_ui": "D002001", "major_topic": false }, { "descriptor": "Amino Acid Transport Systems", "descriptor_ui": "D026905", "major_topic": false }, { "descriptor": "Amino Acids, Branched-Chain", "descriptor_ui": "D000597", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cold Temperature", "descriptor_ui": "D003080", "major_topic": false }, { "descriptor": "Energy Metabolism", "descriptor_ui": "D004734", "major_topic": true }, { "descriptor": "Glucose Intolerance", "descriptor_ui": "D018149", "major_topic": false }, { "descriptor": "Homeostasis", "descriptor_ui": "D006706", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mitochondria", "descriptor_ui": "D008928", "major_topic": false }, { "descriptor": "Mitochondrial Proteins", "descriptor_ui": "D024101", "major_topic": false }, { "descriptor": "Obesity", "descriptor_ui": "D009765", "major_topic": false }, { "descriptor": "Solute Carrier Proteins", "descriptor_ui": "D000070590", "major_topic": false }, { "descriptor": "Thermogenesis", "descriptor_ui": "D022722", "major_topic": true } ], "publication": { "conference_name": null, "date": "2019 Aug", "date_precision": "unknown", "issue": "7771", "normalized_date": null, "pages": "614-619", "proceedings_title": null, "publisher": "", "title": "Nature", "volume": "572", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "BCAA catabolism in brown fat controls energy homeostasis through SLC25A44.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: Branched-chain amino acids (BCAAs) play a key role in energy homeostasis. OBJECTIVE: We aimed to investigate the association between plasma BCAA levels and dyslipidemia in the Japanese population without diabetes mellitus. METHODS: This cross-sectional study included 4952 participants without diabetes mellitus, enrolled in the Tsuruoka Metabolomic Cohort Study. Plasma BCAA levels were measured by capillary electrophoresis-mass spectrometry. Correlations between lipid and BCAA profiles were evaluated by sex-stratified multiple linear regression analyses, after adjusting for confounders. Logistic regression was used to identify associations between BCAAs and metabolic dyslipidemia (MD) defined as triglyceride levels >/=150 mg/dL, high-density lipoprotein cholesterol levels /=140 mg/dL. RESULTS: In both sexes, the levels of individual BCAAs and the total BCAA levels correlated positively with triglyceride levels and negatively with high-density lipoprotein cholesterol levels. Valine, leucine, and total BCAA levels were weakly and positively correlated with LDL-C levels. Increased BCAA levels showed positive associations with MD. However, associations between BCAAs and elevated LDL-C levels were unclear. Furthermore, the associations between BCAA levels and MD regardless of fasting blood sugar (FBS) levels (high or low). Although valine, leucine, and total BCAA levels were weakly associated with elevated LDL-C levels in the high-FBS group, no such association was observed in the low-FBS group. CONCLUSIONS: BCAAs might be associated with MD independently of the FBS level and might play an important role in lipid metabolism and dyslipidemia.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Keiko", "last_name": "Fukushima", "name": null }, { "creator_type": "author", "first_name": "Sei", "last_name": "Harada", "name": null }, { "creator_type": "author", "first_name": "Ayano", "last_name": "Takeuchi", "name": null }, { "creator_type": "author", "first_name": "Ayako", "last_name": "Kurihara", "name": null }, { "creator_type": "author", "first_name": "Miho", "last_name": "Iida", "name": null }, { "creator_type": "author", "first_name": "Kota", "last_name": "Fukai", "name": null }, { "creator_type": "author", "first_name": "Kazuyo", "last_name": "Kuwabara", "name": null }, { "creator_type": "author", "first_name": "Suzuka", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Minako", "last_name": "Matsumoto", "name": null }, { "creator_type": "author", "first_name": "Aya", "last_name": "Hirata", "name": null }, { "creator_type": "author", "first_name": "Miki", "last_name": "Akiyama", "name": null }, { "creator_type": "author", "first_name": "Masaru", "last_name": "Tomita", "name": null }, { "creator_type": "author", "first_name": "Akiyoshi", "last_name": "Hirayama", "name": null }, { "creator_type": "author", "first_name": "Asako", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Chizuru", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Sugimoto", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Sugiyama", "name": null }, { "creator_type": "author", "first_name": "Tomonori", "last_name": "Okamura", "name": null }, { "creator_type": "author", "first_name": "Toru", "last_name": "Takebayashi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.jacl.2019.09.002" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "31601483" } }, "mesh": [ { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Amino Acids, Branched-Chain", "descriptor_ui": "D000597", "major_topic": false }, { "descriptor": "Asian People", "descriptor_ui": "D044466", "major_topic": false }, { "descriptor": "Blood Glucose", "descriptor_ui": "D001786", "major_topic": false }, { "descriptor": "Cholesterol, HDL", "descriptor_ui": "D008076", "major_topic": false }, { "descriptor": "Cholesterol, LDL", "descriptor_ui": "D008078", "major_topic": false }, { "descriptor": "Cohort Studies", "descriptor_ui": "D015331", "major_topic": false }, { "descriptor": "Cross-Sectional Studies", "descriptor_ui": "D003430", "major_topic": false }, { "descriptor": "Diabetes Mellitus", "descriptor_ui": "D003920", "major_topic": false }, { "descriptor": "Dyslipidemias", "descriptor_ui": "D050171", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Insulin", "descriptor_ui": "D007328", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mass Spectrometry", "descriptor_ui": "D013058", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Risk Factors", "descriptor_ui": "D012307", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019 Nov-Dec", "date_precision": "unknown", "issue": "6", "normalized_date": null, "pages": "932-939.e2", "proceedings_title": null, "publisher": "", "title": "Journal of clinical lipidology", "volume": "13", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "Association between dyslipidemia and plasma levels of branched-chain amino acids in the Japanese population without diabetes mellitus.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND AND PURPOSE: The signalling associated with hydrogen sulfide (H(2) S) remains to be established, and recent studies have alluded to the possibility that H(2) S-derived species play important roles. Of particular interest are hydropersulfides (RSSH) and related polysulfides (RSS(n) R, n > 1). This work elucidates the fundamental chemical relationship between these sulfur species as well as examines their biological effects. EXPERIMENTAL APPROACH: Using standard analytical techniques ((1) H-NMR and MS), the equilibrium reactions between H(2) S, disulfides (RSSR), RSSH, dialkyltrisulfides (RSSSR) and thiols (RSH) were examined. Their ability to protect cells from electrophilic and/or oxidative stress was also examined using cell culture. KEY RESULTS: H(2) S, RSSR, RSSH, RSSSR and RSH are all in a dynamic equilibrium. In a biological system, these species can exist simultaneously, and thus, it is difficult to discern which species is (are) the biological effector(s). Treatment of cells with the dialkyl trisulfide cysteine trisulfide (Cys-SSS-Cys) resulted in high intracellular levels of hydropersulfides and protection from electrophilic stress. CONCLUSIONS AND IMPLICATIONS: In aqueous systems, the reaction between H(2) S and RSSR results in the formation of equilibria whereby H(2) S, RSH, RSSR, RSSH and RSSSR are present. In a biological system, any of these species can be responsible for the observed biological activity. These equilibrium species can also be generated via the reaction of RSH with RSSSR. Due to these equilibria, Cys-SSS-Cys can be a method for generating any of the other species. Importantly, HEK293T cells treated with Cys-SSS-Cys results in increased levels of hydropersulfides, allowing examination of the biological effects of RSSH. LINKED ARTICLES: This article is part of a themed section on Chemical Biology of Reactive Sulfur Species. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v176.4/issuetoc.", "classifications": [ { "id": "Akaike", "label": "Group Akaike", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Christopher L.", "last_name": "Bianco", "name": null }, { "creator_type": "author", "first_name": "Takaaki", "last_name": "Akaike", "name": null }, { "creator_type": "author", "first_name": "Tomoaki", "last_name": "Ida", "name": null }, { "creator_type": "author", "first_name": "Peter", "last_name": "Nagy", "name": null }, { "creator_type": "author", "first_name": "Virag", "last_name": "Bogdandi", "name": null }, { "creator_type": "author", "first_name": "John P.", "last_name": "Toscano", "name": null }, { "creator_type": "author", "first_name": "Yoshito", "last_name": "Kumagai", "name": null }, { "creator_type": "author", "first_name": "Catherine F.", "last_name": "Henderson", "name": null }, { "creator_type": "author", "first_name": "Robert N.", "last_name": "Goddu", "name": null }, { "creator_type": "author", "first_name": "Joseph", "last_name": "Lin", "name": null }, { "creator_type": "author", "first_name": "Jon M.", "last_name": "Fukuto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/bph.14372" }, "pmcid": { "normalized": "PMC6346076" }, "pmid": { "normalized": "29809282" } }, "mesh": [ { "descriptor": "Cell Survival", "descriptor_ui": "D002470", "major_topic": false }, { "descriptor": "HEK293 Cells", "descriptor_ui": "D057809", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Sulfides", "descriptor_ui": "D013440", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019 Feb", "date_precision": "unknown", "issue": "4", "normalized_date": null, "pages": "671-683", "proceedings_title": null, "publisher": "", "title": "British journal of pharmacology", "volume": "176", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "The reaction of hydrogen sulfide with disulfides: formation of a stable trisulfide and implications for biological systems.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Humans have a large and gyrencephalic brain. The higher intellectual ability of humans is dependent on the proper development of the brain. Brain malformation is often associated with cognitive dysfunction. It is thus important to know how our brain grows during development. Several animal species have been used as models to understand the mechanisms of brain development, and have provided us with basic information in this regard. It has been revealed that mammalian brain development basically proceeds through a similar process by common mechanisms, including neural stem cell proliferation and neurogenesis. However, humans also display species-specific features in these processes. These differences seem to be important for building the proper human brain structure. Analysis of these human-specific features requires human brain samples, which are difficult to obtain due to both ethical and practical reasons. Nevertheless, brain organoids derived from human pluripotent stem cells can be used as models to study human brain development and pathology because such organoids can partly recapitulate human fetal developmental processes. In this review, we will review some human-specific features during brain development and discuss brain organoid technology as a model system. We will especially focusing on neocortical development.", "classifications": [ { "id": "Eiraku", "label": "Group Eiraku", "parent": "Eiraku", "type": "group" }, { "id": "Eiraku", "label": "Team Eiraku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yusuke", "last_name": "Seto", "name": null }, { "creator_type": "author", "first_name": "Mototsugu", "last_name": "Eiraku", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.neures.2018.09.011" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "30326251" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Models, Biological", "descriptor_ui": "D008954", "major_topic": true }, { "descriptor": "Neocortex", "descriptor_ui": "D019579", "major_topic": false }, { "descriptor": "Organoids", "descriptor_ui": "D009940", "major_topic": false }, { "descriptor": "Species Specificity", "descriptor_ui": "D013045", "major_topic": false }, { "descriptor": "Tissue Culture Techniques", "descriptor_ui": "D046509", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019 Jan", "date_precision": "unknown", "issue": "", "normalized_date": null, "pages": "33-42", "proceedings_title": null, "publisher": "", "title": "Neuroscience research", "volume": "138", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "Human brain development and its in vitro recapitulation.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "In response to the dynamic intra-tumor microenvironment, melanoma cells adopt distinct phenotypic states associated with differential expression of the microphthalmia-associated transcription factor (MITF). The response to hypoxia is driven by hypoxia-inducible transcription factors (HIFs) that reprogram metabolism and promote angiogenesis. HIF1alpha indirectly represses MITF that can activate HIF1alpha expression. Although HIF and MITF share a highly related DNA-binding specificity, it is unclear whether they co-regulate subset of target genes. Moreover, the genomewide impact of hypoxia on melanoma and whether melanoma cell lines representing different phenotypic states exhibit distinct hypoxic responses is unknown. Here we show that three different melanoma cell lines exhibit widely different hypoxia responses with only a core 23 genes regulated in common after 12 hr in hypoxia. Surprisingly, under hypoxia MITF is transiently up-regulated by HIF1alpha and co-regulates a subset of HIF targets including VEGFA. Significantly, we also show that MITF represses itself and also regulates SDHB to control the TCA cycle and suppress pseudo-hypoxia. Our results reveal a previously unsuspected role for MITF in metabolism and the network of factors underpinning the hypoxic response in melanoma.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Pakavarin", "last_name": "Louphrasitthiphol", "name": null }, { "creator_type": "author", "first_name": "Ioanna", "last_name": "Ledaki", "name": null }, { "creator_type": "author", "first_name": "Jagat", "last_name": "Chauhan", "name": null }, { "creator_type": "author", "first_name": "Paola", "last_name": "Falletta", "name": null }, { "creator_type": "author", "first_name": "Robert", "last_name": "Siddaway", "name": null }, { "creator_type": "author", "first_name": "Francesca M.", "last_name": "Buffa", "name": null }, { "creator_type": "author", "first_name": "David R.", "last_name": "Mole", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Colin R.", "last_name": "Goding", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/pcmr.12802" }, "pmcid": { "normalized": "PMC6777998" }, "pmid": { "normalized": "31207090" } }, "mesh": [ { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Citric Acid Cycle", "descriptor_ui": "D002952", "major_topic": true }, { "descriptor": "Gene Expression Regulation, Neoplastic", "descriptor_ui": "D015972", "major_topic": false }, { "descriptor": "Genome, Human", "descriptor_ui": "D015894", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Hypoxia-Inducible Factor 1, alpha Subunit", "descriptor_ui": "D051795", "major_topic": false }, { "descriptor": "Melanoma", "descriptor_ui": "D008545", "major_topic": false }, { "descriptor": "Microphthalmia-Associated Transcription Factor", "descriptor_ui": "D051739", "major_topic": false }, { "descriptor": "Neoplasm Invasiveness", "descriptor_ui": "D009361", "major_topic": false }, { "descriptor": "Succinate Dehydrogenase", "descriptor_ui": "D013385", "major_topic": false }, { "descriptor": "Tumor Hypoxia", "descriptor_ui": "D000072258", "major_topic": true }, { "descriptor": "Up-Regulation", "descriptor_ui": "D015854", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019 Nov", "date_precision": "unknown", "issue": "6", "normalized_date": null, "pages": "792-808", "proceedings_title": null, "publisher": "", "title": "Pigment cell & melanoma research", "volume": "32", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "MITF controls the TCA cycle to modulate the melanoma hypoxia response.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Among seaweed groups, brown algae had characteristically high concentrations of mannitol, and green algae were characterised by fructose. In red algae, metabolite profiles of individual species should be evaluated. Seaweeds are metabolically different from terrestrial plants. However, general metabolite profiles of the three major seaweed groups, the brown, red, and green algae, and the effect of various extraction methods on metabolite profiling results have not been comprehensively explored. In this study, we evaluated the water-soluble metabolites in four brown, five red, and two green algae species collected from two sites in northern Japan, located in the Sea of Japan and the Pacific Ocean. Freeze-dried seaweed samples were processed by methanol-water extraction with or without chloroform and analysed by capillary electrophoresis- and liquid chromatography-mass spectrometry for metabolite characterisation. The metabolite concentration profiles showed distinctive characteristic depends on species and taxonomic groups, whereas the extraction methods did not have a significant effect. Taxonomic differences between the various seaweed metabolite profiles were well defined using only sugar metabolites but no other major compound types. Mannitol was the main sugar metabolites in brown algae, whereas fructose, sucrose, and glucose were found at high concentrations in green algae. In red algae, individual species had some characteristic metabolites, such as sorbitol in Pyropia pseudolinearis and panose in Dasya sessilis. The metabolite profiles generated in this study will be a resource and provide guidance for nutraceutical research studies because the information about metabolites in seaweeds is still very limited compared to that of terrestrial plants.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Shahlizah Sahul", "last_name": "Hamid", "name": null }, { "creator_type": "author", "first_name": "Masataka", "last_name": "Wakayama", "name": null }, { "creator_type": "author", "first_name": "Kensuke", "last_name": "Ichihara", "name": null }, { "creator_type": "author", "first_name": "Katsutoshi", "last_name": "Sakurai", "name": null }, { "creator_type": "author", "first_name": "Yujin", "last_name": "Ashino", "name": null }, { "creator_type": "author", "first_name": "Rie", "last_name": "Kadowaki", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Masaru", "last_name": "Tomita", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/s00425-019-03134-1" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "30891648" } }, "mesh": [ { "descriptor": "Chlorophyta", "descriptor_ui": "D000460", "major_topic": false }, { "descriptor": "Cluster Analysis", "descriptor_ui": "D016000", "major_topic": false }, { "descriptor": "Fructose", "descriptor_ui": "D005632", "major_topic": false }, { "descriptor": "Mannitol", "descriptor_ui": "D008353", "major_topic": false }, { "descriptor": "Metabolome", "descriptor_ui": "D055442", "major_topic": true }, { "descriptor": "Phaeophyceae", "descriptor_ui": "D000459", "major_topic": false }, { "descriptor": "Rhodophyta", "descriptor_ui": "D000461", "major_topic": false }, { "descriptor": "Seaweed", "descriptor_ui": "D012624", "major_topic": false }, { "descriptor": "Species Specificity", "descriptor_ui": "D013045", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019 Jun", "date_precision": "unknown", "issue": "6", "normalized_date": null, "pages": "1921-1947", "proceedings_title": null, "publisher": "", "title": "Planta", "volume": "249", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "Metabolome profiling of various seaweed species discriminates between brown, red, and green algae.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Osteocytes regulate bone remodeling, especially in response to mechanical loading and unloading of bone, with nitric oxide reported to play an important role in that process. In the present study, we found that 8-nitroguanosine 3',5'-cyclic monophosphate (8-nitro-cGMP), a second messenger of nitric oxide in various types of cells, was produced by osteocytes in bone tissue as well as cultured osteocytic Ocy454 cells. The amount of 8-nitro-cGMP in Ocy454 cells increased during incubation with parathyroid hormone or prostaglandin E(2), both of which are known to upregulate receptor activator of nuclear factor-kappaB ligand (RANKL) mRNA expression in osteocytes. On the other hand, exogenous 8-nitro-cGMP did not have effects on either the presence or absence of these bioactive substances. Furthermore, neither an inhibitor of nitric oxide synthase nor 8-bromo-cGMP, a cell-permeable analog of cGMP, showed remarkable effects on mRNA expression of sclerostin or RANKL. These results indicate that neither nitric oxide nor its downstream compounds, including 8-nitro-cGMP, alone are sufficient for induction of functional changes in osteocytes.", "classifications": [ { "id": "Akaike", "label": "Group Akaike", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Kazuhiro", "last_name": "Nagayama", "name": null }, { "creator_type": "author", "first_name": "Yoichi", "last_name": "Miyamoto", "name": null }, { "creator_type": "author", "first_name": "Kotaro", "last_name": "Kaneko", "name": null }, { "creator_type": "author", "first_name": "Kentaro", "last_name": "Yoshimura", "name": null }, { "creator_type": "author", "first_name": "Kiyohito", "last_name": "Sasa", "name": null }, { "creator_type": "author", "first_name": "Takaaki", "last_name": "Akaike", "name": null }, { "creator_type": "author", "first_name": "Shigemoto", "last_name": "Fujii", "name": null }, { "creator_type": "author", "first_name": "Eri", "last_name": "Izumida", "name": null }, { "creator_type": "author", "first_name": "Risa", "last_name": "Uyama", "name": null }, { "creator_type": "author", "first_name": "Daichi", "last_name": "Chikazu", "name": null }, { "creator_type": "author", "first_name": "Koutaro", "last_name": "Maki", "name": null }, { "creator_type": "author", "first_name": "Ryutaro", "last_name": "Kamijo", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/s11626-018-0304-0" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "30397855" } }, "mesh": [ { "descriptor": "Adaptor Proteins, Signal Transducing", "descriptor_ui": "D048868", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "Cyclic GMP", "descriptor_ui": "D006152", "major_topic": false }, { "descriptor": "Dinoprostone", "descriptor_ui": "D015232", "major_topic": false }, { "descriptor": "Extracellular Matrix Proteins", "descriptor_ui": "D016326", "major_topic": false }, { "descriptor": "Femur", "descriptor_ui": "D005269", "major_topic": false }, { "descriptor": "Glycoproteins", "descriptor_ui": "D006023", "major_topic": false }, { "descriptor": "Intercellular Signaling Peptides and Proteins", "descriptor_ui": "D036341", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Osteocytes", "descriptor_ui": "D010011", "major_topic": false }, { "descriptor": "Osteoprotegerin", "descriptor_ui": "D053244", "major_topic": false }, { "descriptor": "Parathyroid Hormone", "descriptor_ui": "D010281", "major_topic": false }, { "descriptor": "RANK Ligand", "descriptor_ui": "D053245", "major_topic": false }, { "descriptor": "RNA, Messenger", "descriptor_ui": "D012333", "major_topic": false }, { "descriptor": "Tumor Necrosis Factor-alpha", "descriptor_ui": "D014409", "major_topic": false }, { "descriptor": "Up-Regulation", "descriptor_ui": "D015854", "major_topic": true } ], "publication": { "conference_name": null, "date": "2019 Jan", "date_precision": "unknown", "issue": "1", "normalized_date": null, "pages": "45-51", "proceedings_title": null, "publisher": "", "title": "In vitro cellular & developmental biology. Animal", "volume": "55", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "Production of 8-nitro-cGMP in osteocytic cells and its upregulation by parathyroid hormone and prostaglandin E(2).", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "PURPOSE: To evaluate the prevalence and risk factors of and the relationship between meibomian gland dysfunction (MGD) and dry eye (DE) in Japan. DESIGN: A population-based cross-sectional study. METHODS: Participants filled in questionnaires regarding ocular symptoms, systemic diseases, and lifestyle factors. Meibomian gland-related parameters and tear film-related parameters were evaluated. Risk factors for MGD and DE were analyzed by using univariate and multivariate logistic regression. Age-specific prevalence of MGD and DE was estimated by using a general additive model with degree-3 natural splines. The structural relation between MGD and DE was assessed by factor analysis using the principal components method and promax rotation. RESULTS: A total of 356 residents of Takushima Island (133 males, 223 females) at the mean +/- SD age of 55.5 +/- 22.4 years (range, 6-96 years) were enrolled. The prevalence of MGD and DE was 32.9% and 33.4%, respectively, with a coexistence rate of 12.9%. The prevalence of MGD was associated with male sex (odds ratio [OR], 2.42), age (OR per decade increment,1.53), and oral intake of lipid-lowering agents (OR, 3.22). The prevalence of DE was associated with female sex (OR, 3.36), contact lens wear (OR, 2.84), conjunctivochalasis (OR, 2.57), and lid margin abnormalities (OR, 3.16). The age-specific prevalence of MGD and DE differed, and factor analysis for 16 parameters showed that MGD and DE had independent hidden sources (interfactor correlation, -0.017). CONCLUSIONS: MGD and DE are common in this population. Although their ocular symptoms are similar, the pathogenesis of MGD differs from that of DE.", "classifications": [ { "id": "Suzuki", "label": "Group Suzuki", "parent": "Takekawa", "type": "group" }, { "id": "Takekawa", "label": "Team Takekawa", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Reiko", "last_name": "Arita", "name": null }, { "creator_type": "author", "first_name": "Takanori", "last_name": "Mizoguchi", "name": null }, { "creator_type": "author", "first_name": "Motoko", "last_name": "Kawashima", "name": null }, { "creator_type": "author", "first_name": "Shima", "last_name": "Fukuoka", "name": null }, { "creator_type": "author", "first_name": "Shizuka", "last_name": "Koh", "name": null }, { "creator_type": "author", "first_name": "Rika", "last_name": "Shirakawa", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Naoyuki", "last_name": "Morishige", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.ajo.2019.02.024" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "30851269" } }, "mesh": [ { "descriptor": "Adolescent", "descriptor_ui": "D000293", "major_topic": false }, { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Age Distribution", "descriptor_ui": "D017677", "major_topic": false }, { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Aged, 80 and over", "descriptor_ui": "D000369", "major_topic": false }, { "descriptor": "Child", "descriptor_ui": "D002648", "major_topic": false }, { "descriptor": "Dry Eye Syndromes", "descriptor_ui": "D015352", "major_topic": false }, { "descriptor": "Factor Analysis, Statistical", "descriptor_ui": "D005163", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Japan", "descriptor_ui": "D007564", "major_topic": false }, { "descriptor": "Logistic Models", "descriptor_ui": "D016015", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Meibomian Gland Dysfunction", "descriptor_ui": "D000080343", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Risk Factors", "descriptor_ui": "D012307", "major_topic": false }, { "descriptor": "Sex Distribution", "descriptor_ui": "D017678", "major_topic": false }, { "descriptor": "Young Adult", "descriptor_ui": "D055815", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019 Nov", "date_precision": "unknown", "issue": "", "normalized_date": null, "pages": "410-418", "proceedings_title": null, "publisher": "", "title": "American journal of ophthalmology", "volume": "207", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "Meibomian Gland Dysfunction and Dry Eye Are Similar but Different Based on a Population-Based Study: The Hirado-Takushima Study in Japan.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Magic-number gold nanoclusters are atomically precise nanomaterials that have enabled unprecedented insight into structure-property relationships in nanoscience. Thiolates are the most common ligand, binding to the cluster via a staple motif in which only central gold atoms are in the metallic state. The lack of other strongly bound ligands for nanoclusters with different bonding modes has been a significant limitation in the field. Here, we report a previously unknown ligand for gold(0) nanoclusters-N-heterocyclic carbenes (NHCs)-which feature a robust metal-carbon single bond and impart high stability to the corresponding gold cluster. The addition of a single NHC to gold nanoclusters results in significantly improved stability and catalytic properties in the electrocatalytic reduction of CO(2). By varying the conditions, nature and number of equivalents of the NHC, predominantly or exclusively monosubstituted NHC-functionalized clusters result. Clusters can also be obtained with up to five NHCs, as a mixture of species.", "classifications": [ { "id": "Nanbo", "label": "Group Nanbo", "parent": "Tsuchiya", "type": "group" }, { "id": "Tsuchiya", "label": "Team Tsuchiya", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Mina R.", "last_name": "Narouz", "name": null }, { "creator_type": "author", "first_name": "Kimberly M.", "last_name": "Osten", "name": null }, { "creator_type": "author", "first_name": "Phillip J.", "last_name": "Unsworth", "name": null }, { "creator_type": "author", "first_name": "Renee W. Y.", "last_name": "Man", "name": null }, { "creator_type": "author", "first_name": "Kirsi", "last_name": "Salorinne", "name": null }, { "creator_type": "author", "first_name": "Shinjiro", "last_name": "Takano", "name": null }, { "creator_type": "author", "first_name": "Ryohei", "last_name": "Tomihara", "name": null }, { "creator_type": "author", "first_name": "Sami", "last_name": "Kaappa", "name": null }, { "creator_type": "author", "first_name": "Sami", "last_name": "Malola", "name": null }, { "creator_type": "author", "first_name": "Cao-Thang", "last_name": "Dinh", "name": null }, { "creator_type": "author", "first_name": "J. Daniel", "last_name": "Padmos", "name": null }, { "creator_type": "author", "first_name": "Kennedy", "last_name": "Ayoo", "name": null }, { "creator_type": "author", "first_name": "Patrick J.", "last_name": "Garrett", "name": null }, { "creator_type": "author", "first_name": "Masakazu", "last_name": "Nambo", "name": null }, { "creator_type": "author", "first_name": "J. Hugh", "last_name": "Horton", "name": null }, { "creator_type": "author", "first_name": "Edward H.", "last_name": "Sargent", "name": null }, { "creator_type": "author", "first_name": "Hannu", "last_name": "Hakkinen", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Tsukuda", "name": null }, { "creator_type": "author", "first_name": "Cathleen M.", "last_name": "Crudden", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41557-019-0246-5" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "30988416" } }, "mesh": [], "publication": { "conference_name": null, "date": "2019 May", "date_precision": "unknown", "issue": "5", "normalized_date": null, "pages": "419-425", "proceedings_title": null, "publisher": "", "title": "Nature chemistry", "volume": "11", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "N-heterocyclic carbene-functionalized magic-number gold nanoclusters.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: Salivary secretion is an important parameter reflecting the health status of an individual and has been used clinically for the diagnosis of various oral diseases, such as xerostomia. Salivary metabolomic profiling is considered an emerging potential tool for the detection of various systemic diseases. To our knowledge, this is the first study to investigate the quantitative relationship between salivary secretion volume and salivary metabolomic profile. METHODS: To evaluate inter- and intra-day variations in salivary secretion, 234 saliva samples were collected three times per day for three days from 13 subjects and analyzed. Capillary electrophoresis-mass spectrometry was used for non-targeted quantification of water-soluble metabolites. RESULTS: No significant inter- or intra-day variations were observed in salivary secretion volume. No significant inter-day variations were observed in metabolomic patterns. In contrast, significant intra-day variations were observed in salivary metabolomic profiles. The difference was more obvious for stimulated saliva than for unstimulated saliva. These profile changes were independent of salivary secretion volume. CONCLUSIONS: Our results indicated that diurnal change had a greater effect on salivary metabolomic profiles than the other factors. Hence, sampling time should be tightly controlled to minimize unexpected bias in the clinical use of salivary metabolomics.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Norishige", "last_name": "Kawanishi", "name": null }, { "creator_type": "author", "first_name": "Noriyuki", "last_name": "Hoshi", "name": null }, { "creator_type": "author", "first_name": "Sugimoto", "last_name": "Masahiro", "name": null }, { "creator_type": "author", "first_name": "Ayame", "last_name": "Enomoto", "name": null }, { "creator_type": "author", "first_name": "Sana", "last_name": "Ota", "name": null }, { "creator_type": "author", "first_name": "Miku", "last_name": "Kaneko", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Masaru", "last_name": "Tomita", "name": null }, { "creator_type": "author", "first_name": "Katsuhiko", "last_name": "Kimoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.cca.2018.11.030" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "30481500" } }, "mesh": [ { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Metabolomics", "descriptor_ui": "D055432", "major_topic": false }, { "descriptor": "Saliva", "descriptor_ui": "D012463", "major_topic": false }, { "descriptor": "Time Factors", "descriptor_ui": "D013997", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019 Feb", "date_precision": "unknown", "issue": "", "normalized_date": null, "pages": "41-48", "proceedings_title": null, "publisher": "", "title": "Clinica chimica acta; international journal of clinical chemistry", "volume": "489", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "Effects of inter-day and intra-day variation on salivary metabolomic profiles.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND AND AIM: Septal thickness (ST) can predict a malignant branch-duct (BD) and mixed-type intraductal papillary mucinous neoplasm (IPMN) of the pancreas, but its cut-off value has not been established. The aim of the present study was to determine the optimal ST cut-off value to predict malignancy using endoscopic ultrasound (EUS). METHODS: We retrospectively identified 200 patients with IPMN, including 132 with BD- and mixed-IPMN, who underwent surgical resection between 1989 and 2017. ST was defined as the septum or lesion wall with the maximum diameter in BD- and mixed-IPMN. The possibility of ST as a malignant predictor was examined, as well as the diagnostic ability of ST combined with mural nodule (MN) height for malignant IPMN. RESULTS: Among the 132 IPMN patients, pathological diagnosis was benign in 81 (61.4%) and malignant in 51 (38.6%). Area under the curve for the diagnosis of malignancy using ST was 0.74 for pathological specimens, 0.70 for EUS and 0.56 for computed tomography. Multivariate analysis showed that the odds ratios for ST >/=2.5 mm and MN height >/=5 mm were 3.51 [95% confidence interval (CI), 1.55-7.97, P = 0.003] and 3.36 (95% CI, 1.52-7.45, P = 0.003), respectively. CONCLUSIONS: Septal thickness was an independent predictive factor similar to MN height for malignant IPMN in a multivariate analysis. The ST on EUS appeared to be the thickness of a fibrotic septum associated with the malignant transformation of IPMN. An ST cut-off value of 2.5 mm might provide an accurate prediction of malignant IPMN.", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Hiromichi", "last_name": "Iwaya", "name": null }, { "creator_type": "author", "first_name": "Susumu", "last_name": "Hijioka", "name": null }, { "creator_type": "author", "first_name": "Nobumasa", "last_name": "Mizuno", "name": null }, { "creator_type": "author", "first_name": "Takamichi", "last_name": "Kuwahara", "name": null }, { "creator_type": "author", "first_name": "Nozomi", "last_name": "Okuno", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Tajika", "name": null }, { "creator_type": "author", "first_name": "Tsutomu", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Ishihara", "name": null }, { "creator_type": "author", "first_name": "Yutaka", "last_name": "Hirayama", "name": null }, { "creator_type": "author", "first_name": "Sachiyo", "last_name": "Onishi", "name": null }, { "creator_type": "author", "first_name": "Ayako", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Naosuke", "last_name": "Kuraoka", "name": null }, { "creator_type": "author", "first_name": "Shinpei", "last_name": "Matsumoto", "name": null }, { "creator_type": "author", "first_name": "Petcharee", "last_name": "Polmanee", "name": null }, { "creator_type": "author", "first_name": "Yasuhiro", "last_name": "Shimizu", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null }, { "creator_type": "author", "first_name": "Yasumasa", "last_name": "Niwa", "name": null }, { "creator_type": "author", "first_name": "Kiichi", "last_name": "Tamada", "name": null }, { "creator_type": "author", "first_name": "Akio", "last_name": "Ido", "name": null }, { "creator_type": "author", "first_name": "Kazuo", "last_name": "Hara", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/den.13408" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "30920028" } }, "mesh": [ { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Aged, 80 and over", "descriptor_ui": "D000369", "major_topic": false }, { "descriptor": "Carcinoma, Pancreatic Ductal", "descriptor_ui": "D021441", "major_topic": false }, { "descriptor": "Endosonography", "descriptor_ui": "D019160", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Follow-Up Studies", "descriptor_ui": "D005500", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Neoplasm Staging", "descriptor_ui": "D009367", "major_topic": false }, { "descriptor": "Pancreas", "descriptor_ui": "D010179", "major_topic": false }, { "descriptor": "Pancreatic Neoplasms", "descriptor_ui": "D010190", "major_topic": false }, { "descriptor": "Predictive Value of Tests", "descriptor_ui": "D011237", "major_topic": false }, { "descriptor": "Retrospective Studies", "descriptor_ui": "D012189", "major_topic": false }, { "descriptor": "Tomography, X-Ray Computed", "descriptor_ui": "D014057", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019 Nov", "date_precision": "unknown", "issue": "6", "normalized_date": null, "pages": "672-681", "proceedings_title": null, "publisher": "", "title": "Digestive endoscopy : official journal of the Japan Gastroenterological Endoscopy Society", "volume": "31", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "Usefulness of septal thickness measurement on endoscopic ultrasound as a predictor of malignancy of branched-duct and mixed-type intraductal papillary mucinous neoplasm of the pancreas.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Primary central nervous system lymphoma (PCNSL) is a rare subtype of lymphoma that arises within the brain or the eyes. PCNSL recurs within the central nervous system (CNS) in most relapsed cases, whereas extra‐CNS relapse is experienced in rare cases. The present study aimed at identifying the presence of common precursor cells (CPC) for primary intra‐ and relapsed extra‐CNS tumors, and further assessing the initiating events in bone marrow (BM). Targeted deep sequencing was carried out for five paired primary intra‐ and relapsed extra‐CNS tumors of PCNSL. Two to five mutations were shared by each pair of intra‐ and extra‐CNS tumors. In particular, MYD88 mutations, L265P in three and P258L in one, were shared by four pairs. Unique somatic mutations were observed in all five intra‐CNS tumors and in four out of five extra‐CNS tumors. Remarkably, IgH clones in the intra‐ and the extra‐CNS tumors in two pairs were distinct from each other, whereas one pair of tumors shared identical monoclonal IgH rearrangement. In a cohort of 23 PCNSL patients, L265P MYD88 mutations were examined in tumor‐free BM mononuclear cells (MNC) in which the PCNSL tumors had L265P MYD88 mutations. L265P MYD88 mutations were detected by a droplet digital PCR method in nine out of 23 bone marrow mononuclear cells. These results suggest that intra‐ and extra‐tumors are derived from CPC with MYD88 mutations in most PCNSL, arising either before or after IgH rearrangement. The initiating MYD88 mutations may occur during B‐cell differentiation in BM.", "classifications": [ { "id": "Nishikii", "label": "Group Nishikii", "parent": "Shintaku", "type": "group" }, { "id": "Shintaku", "label": "Team Shintaku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Keiichiro", "last_name": "Hattori", "name": null }, { "creator_type": "author", "first_name": "Mamiko", "last_name": "Sakata‐Yanagimoto", "name": null }, { "creator_type": "author", "first_name": "Manabu", "last_name": "Kusakabe", "name": null }, { "creator_type": "author", "first_name": "Toru", "last_name": "Nanmoku", "name": null }, { "creator_type": "author", "first_name": "Yasuhito", "last_name": "Suehara", "name": null }, { "creator_type": "author", "first_name": "Ryota", "last_name": "Matsuoka", "name": null }, { "creator_type": "author", "first_name": "Masayuki", "last_name": "Noguchi", "name": null }, { "creator_type": "author", "first_name": "Yasuhisa", "last_name": "Yokoyama", "name": null }, { "creator_type": "author", "first_name": "Takayasu", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Naoki", "last_name": "Kurita", "name": null }, { "creator_type": "author", "first_name": "Hidekazu", "last_name": "Nishikii", "name": null }, { "creator_type": "author", "first_name": "Naoshi", "last_name": "Obara", "name": null }, { "creator_type": "author", "first_name": "Shingo", "last_name": "Takano", "name": null }, { "creator_type": "author", "first_name": "Eiichi", "last_name": "Ishikawa", "name": null }, { "creator_type": "author", "first_name": "Akira", "last_name": "Matsumura", "name": null }, { "creator_type": "author", "first_name": "Masafumi", "last_name": "Muratani", "name": null }, { "creator_type": "author", "first_name": "Yuichi", "last_name": "Hasegawa", "name": null }, { "creator_type": "author", "first_name": "Shigeru", "last_name": "Chiba", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/cas.13848" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "30353605" } }, "mesh": [ { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Central Nervous System Neoplasms", "descriptor_ui": "D016543", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Gene Rearrangement", "descriptor_ui": "D015321", "major_topic": false }, { "descriptor": "High-Throughput Nucleotide Sequencing", "descriptor_ui": "D059014", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Immunoglobulin Heavy Chains", "descriptor_ui": "D007143", "major_topic": false }, { "descriptor": "Lymphoma, B-Cell", "descriptor_ui": "D016393", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": false }, { "descriptor": "Myeloid Differentiation Factor 88", "descriptor_ui": "D053594", "major_topic": false }, { "descriptor": "Neoplasm Recurrence, Local", "descriptor_ui": "D009364", "major_topic": true }, { "descriptor": "Neoplastic Stem Cells", "descriptor_ui": "D014411", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019 Jan", "date_precision": "unknown", "issue": "1", "normalized_date": null, "pages": "401-407", "proceedings_title": null, "publisher": "", "title": "Cancer Science", "volume": "110", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "Genetic evidence implies that primary and relapsed tumors arise from common precursor cells in primary central nervous system lymphoma.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Cellular signaling regulates various cellular functions via protein phosphorylation. Phosphoproteomic data potentially include information for a global regulatory network from signaling to cellular functions, but a procedure to reconstruct this network using such data has yet to be established. In this paper, we provide a procedure to reconstruct a global regulatory network from signaling to cellular functions from phosphoproteomic data by integrating prior knowledge of cellular functions and inference of the kinase-substrate relationships (KSRs). We used phosphoproteomic data from insulin-stimulated Fao hepatoma cells and identified protein phosphorylation regulated by insulin specifically over-represented in cellular functions in the KEGG database. We inferred kinases for protein phosphorylation by KSRs, and connected the kinases in the insulin signaling layer to the phosphorylated proteins in the cellular functions, revealing that the insulin signal is selectively transmitted via the Pi3k-Akt and Erk signaling pathways to cellular adhesions and RNA maturation, respectively. Thus, we provide a method to reconstruct global regulatory network from signaling to cellular functions based on phosphoproteomic data.", "classifications": [ { "id": "Kuroda", "label": "Group Kuroda", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Kentaro", "last_name": "Kawata", "name": null }, { "creator_type": "author", "first_name": "Katsuyuki", "last_name": "Yugi", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Hatano", "name": null }, { "creator_type": "author", "first_name": "Toshiya", "last_name": "Kokaji", "name": null }, { "creator_type": "author", "first_name": "Yoko", "last_name": "Tomizawa", "name": null }, { "creator_type": "author", "first_name": "Masashi", "last_name": "Fujii", "name": null }, { "creator_type": "author", "first_name": "Shinsuke", "last_name": "Uda", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Kubota", "name": null }, { "creator_type": "author", "first_name": "Masaki", "last_name": "Matsumoto", "name": null }, { "creator_type": "author", "first_name": "Keiichi I.", "last_name": "Nakayama", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Kuroda", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/gtc.12655" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "30417516" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cells", "descriptor_ui": "D002477", "major_topic": false }, { "descriptor": "Gene Regulatory Networks", "descriptor_ui": "D053263", "major_topic": true }, { "descriptor": "Insulin", "descriptor_ui": "D007328", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Phosphopeptides", "descriptor_ui": "D010748", "major_topic": false }, { "descriptor": "Phosphoproteins", "descriptor_ui": "D010750", "major_topic": false }, { "descriptor": "Phosphorylation", "descriptor_ui": "D010766", "major_topic": false }, { "descriptor": "Protein Kinases", "descriptor_ui": "D011494", "major_topic": false }, { "descriptor": "Proteomics", "descriptor_ui": "D040901", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": true }, { "descriptor": "Substrate Specificity", "descriptor_ui": "D013379", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019 Jan", "date_precision": "unknown", "issue": "1", "normalized_date": null, "pages": "82-93", "proceedings_title": null, "publisher": "", "title": "Genes to cells : devoted to molecular & cellular mechanisms", "volume": "24", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "Reconstruction of global regulatory network from signaling to cellular functions using phosphoproteomic data.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: Asthma-chronic obstructive pulmonary disease overlap (ACO) has frequent exacerbations and a poor quality of life and prognosis compared with those of chronic obstructive pulmonary disease alone. However, the pathogenesis of ACO has not been fully elucidated yet. OBJECTIVES: The aim of this study was to investigate nitrosative stress, which causes a redox imbalance and tissue inflammation in the airways of patients with ACO, and to evaluate the relationship between nitrosative stress and the clinical course in study subjects. METHODS: Thirty healthy subjects and 56 asthmatic patients participated in this study. The asthmatic patients were divided into 33 asthmatic patients and 23 patients with ACO. The study subjects had been followed prospectively for 2 years to evaluate the clinical course. Nitrosative stress was evaluated based on the production of 3-nitrotyrosine (3-NT) in sputum cells. RESULTS: Production of 3-NT was significantly enhanced in patients with ACO compared with that in asthmatic patients. Amounts of reactive persulfides and polysulfides, newly identified powerful antioxidants, were significantly decreased in the ACO group. Baseline levels of 3-NT were significantly correlated with the frequency of exacerbations and decrease in FEV(1) adjusted by age, smoking history, and blood eosinophil count. The 3-NT-positive cells were also significantly correlated with amounts of proinflammatory chemokines and cytokines. CONCLUSIONS: These findings suggested that greater nitrosative stress occurred in the airways of patients with ACO, and the degree of nitrosative stress was correlated with an impairment in the clinical course. Nitrosative stress might be related to the pathogenesis of ACO.", "classifications": [ { "id": "Akaike", "label": "Group Akaike", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yorihiko", "last_name": "Kyogoku", "name": null }, { "creator_type": "author", "first_name": "Hisatoshi", "last_name": "Sugiura", "name": null }, { "creator_type": "author", "first_name": "Tomohiro", "last_name": "Ichikawa", "name": null }, { "creator_type": "author", "first_name": "Tadahisa", "last_name": "Numakura", "name": null }, { "creator_type": "author", "first_name": "Akira", "last_name": "Koarai", "name": null }, { "creator_type": "author", "first_name": "Mitsuhiro", "last_name": "Yamada", "name": null }, { "creator_type": "author", "first_name": "Naoya", "last_name": "Fujino", "name": null }, { "creator_type": "author", "first_name": "Yutaka", "last_name": "Tojo", "name": null }, { "creator_type": "author", "first_name": "Katsuhiro", "last_name": "Onodera", "name": null }, { "creator_type": "author", "first_name": "Rie", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Kei", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Hirohito", "last_name": "Sano", "name": null }, { "creator_type": "author", "first_name": "Shun", "last_name": "Yamanaka", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Itakura", "name": null }, { "creator_type": "author", "first_name": "Ayumi", "last_name": "Mitsune", "name": null }, { "creator_type": "author", "first_name": "Tsutomu", "last_name": "Tamada", "name": null }, { "creator_type": "author", "first_name": "Takaaki", "last_name": "Akaike", "name": null }, { "creator_type": "author", "first_name": "Masakazu", "last_name": "Ichinose", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.jaci.2019.04.023" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "31077687" } }, "mesh": [ { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Asthma", "descriptor_ui": "D001249", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Nitrosative Stress", "descriptor_ui": "D000073039", "major_topic": false }, { "descriptor": "Pulmonary Disease, Chronic Obstructive", "descriptor_ui": "D029424", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019 Oct", "date_precision": "unknown", "issue": "4", "normalized_date": null, "pages": "972-983.e14", "proceedings_title": null, "publisher": "", "title": "The Journal of allergy and clinical immunology", "volume": "144", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "Nitrosative stress in patients with asthma-chronic obstructive pulmonary disease overlap.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND AND PURPOSE: Doxorubicin is a highly effective anticancer agent but eventually induces cardiotoxicity associated with increased production of ROS. We previously reported that a pathological protein interaction between TRPC3 channels and NADPH oxidase 2 (Nox2) contributed to doxorubicin-induced cardiac atrophy in mice. Here we have investigated the effects of ibudilast, a drug already approved for clinical use and known to block doxorubicin-induced cytotoxicity, on the TRPC3-Nox2 complex. We specifically sought evidence that this drug attenuated doxorubicin-induced systemic tissue wasting in mice. EXPERIMENTAL APPROACH: We used the RAW264.7 macrophage cell line to screen 1,271 clinically approved chemical compounds, evaluating functional interactions between TRPC3 channels and Nox2, by measuring Nox2 protein stability and ROS production, with and without exposure to doxorubicin. In male C57BL/6 mice, samples of cardiac and gastrocnemius muscle were taken and analysed with morphometric, immunohistochemical, RT-PCR and western blot methods. In the passive smoking model, cells were exposed to DMEM containing cigarette sidestream smoke. KEY RESULTS: Ibudilast, an anti-asthmatic drug, attenuated ROS-mediated muscle toxicity induced by doxorubicin treatment or passive smoking, by inhibiting the functional interactions between TRPC3 channels and Nox2, without reducing TRPC3 channel activity. CONCLUSIONS AND IMPLICATIONS: These results indicate a common mechanism underlying induction of systemic tissue wasting by doxorubicin. They also suggest that ibudilast could be repurposed to prevent muscle toxicity caused by anticancer drugs or passive smoking.", "classifications": [ { "id": "Nishida", "label": "Group Nishida", "parent": "Nishida", "type": "group" }, { "id": "Nishimura", "label": "Group Nishimura", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Kazuhiro", "last_name": "Nishiyama", "name": null }, { "creator_type": "author", "first_name": "Takuro", "last_name": "Numaga-Tomita", "name": null }, { "creator_type": "author", "first_name": "Yasuyuki", "last_name": "Fujimoto", "name": null }, { "creator_type": "author", "first_name": "Tomohiro", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Chiemi", "last_name": "Toyama", "name": null }, { "creator_type": "author", "first_name": "Akiyuki", "last_name": "Nishimura", "name": null }, { "creator_type": "author", "first_name": "Tomohiro", "last_name": "Yamashita", "name": null }, { "creator_type": "author", "first_name": "Naoya", "last_name": "Matsunaga", "name": null }, { "creator_type": "author", "first_name": "Satoru", "last_name": "Koyanagi", "name": null }, { "creator_type": "author", "first_name": "Yasu-Taka", "last_name": "Azuma", "name": null }, { "creator_type": "author", "first_name": "Yuko", "last_name": "Ibuki", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Uchida", "name": null }, { "creator_type": "author", "first_name": "Shigehiro", "last_name": "Ohdo", "name": null }, { "creator_type": "author", "first_name": "Motohiro", "last_name": "Nishida", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/bph.14777" }, "pmcid": { "normalized": "PMC6715615" }, "pmid": { "normalized": "31241172" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Antineoplastic Agents", "descriptor_ui": "D000970", "major_topic": false }, { "descriptor": "Cardiotoxicity", "descriptor_ui": "D066126", "major_topic": false }, { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "Cell Survival", "descriptor_ui": "D002470", "major_topic": false }, { "descriptor": "Doxorubicin", "descriptor_ui": "D004317", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Indolizines", "descriptor_ui": "D007212", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Myocytes, Cardiac", "descriptor_ui": "D032383", "major_topic": false }, { "descriptor": "NADPH Oxidase 2", "descriptor_ui": "D000074662", "major_topic": false }, { "descriptor": "Pyrazoles", "descriptor_ui": "D011720", "major_topic": false }, { "descriptor": "Pyridines", "descriptor_ui": "D011725", "major_topic": false }, { "descriptor": "Rats, Sprague-Dawley", "descriptor_ui": "D017207", "major_topic": false }, { "descriptor": "Reactive Oxygen Species", "descriptor_ui": "D017382", "major_topic": false }, { "descriptor": "Tobacco Smoke Pollution", "descriptor_ui": "D014028", "major_topic": false }, { "descriptor": "TRPC Cation Channels", "descriptor_ui": "D050052", "major_topic": false }, { "descriptor": "Wasting Syndrome", "descriptor_ui": "D019282", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019 Sep", "date_precision": "unknown", "issue": "18", "normalized_date": null, "pages": "3723-3738", "proceedings_title": null, "publisher": "", "title": "British journal of pharmacology", "volume": "176", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "Ibudilast attenuates doxorubicin-induced cytotoxicity by suppressing formation of TRPC3 channel and NADPH oxidase 2 protein complexes.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The unidirectional motion of a camphor boat along an annular water channel is observable. When camphor boats are placed in a water channel, both homogeneous and inhomogeneous states occur as collective motions, depending on the number of boats. The inhomogeneous state is a type of congestion, that is, the velocities of the boats change with temporal oscillation, and the shock wave appears along the line of travel of the boats. The unidirectional motion of a single camphor boat and the homogeneous state can be represented by traveling wave solutions in a mathematical model. Because the experimental results described here are thought of as a type of bifurcation phenomenon, the destabilization of traveling wave solutions may indicate the emergence of congestion. We previously attempted to study a linearized eigenvalue problem associated with a traveling wave solution. However, the problem is too difficult to analyze rigorously, even for just two camphor boats. Therefore we developed a center manifold theory and derived a reduced model in our previous work. In the present paper, we study the reduced model and show that the original model and our reduced model qualitatively exhibit the same properties by applying numerical techniques. Moreover, we demonstrate that the numerical results obtained in our models for camphor boats are quite similar to those in a car-following model, the OV model, but there are some different features between our reduced model and a typical OV model.", "classifications": [ { "id": "Nagayama", "label": "Group Nagayama", "parent": "Fujiwara", "type": "group" }, { "id": "Fujiwara", "label": "Team Fujiwara", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Kota", "last_name": "Ikeda", "name": null }, { "creator_type": "author", "first_name": "Shin-Ichiro", "last_name": "Ei", "name": null }, { "creator_type": "author", "first_name": "Masaharu", "last_name": "Nagayama", "name": null }, { "creator_type": "author", "first_name": "Mamoru", "last_name": "Okamoto", "name": null }, { "creator_type": "author", "first_name": "Akiyasu", "last_name": "Tomoeda", "name": null } ], "identifiers": { "doi": { "normalized": "10.1103/physreve.99.062208" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "31330577" } }, "mesh": [], "publication": { "conference_name": null, "date": "2019 Jun", "date_precision": "unknown", "issue": "6-1", "normalized_date": null, "pages": "062208", "proceedings_title": null, "publisher": "", "title": "Physical review. E", "volume": "99", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "Reduced model of a reaction-diffusion system for the collective motion of camphor boats.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Wound epidermis (WE) and the apical epithelial cap (AEC) are believed to trigger regeneration of amputated appendages such as limb and tail in amphibians by producing certain secreted signaling molecules. To date, however, only limited information about the molecular signatures of these epidermal structures is available. Here we used a transgenic Xenopus laevis line harboring the enhanced green fluorescent protein (egfp) gene under control of an es1 gene regulatory sequence to isolate WE/AEC cells by performing fluorescence-activated cell sorting during the time course of tail regeneration (day 1, day 2, day 3 and day 4 after amputation). Time-course transcriptome analysis of these isolated WE/AEC cells revealed that more than 8,000 genes, including genes involved in signaling pathways such as those of reactive oxygen species, fibroblast growth factor (FGF), canonical and non-canonical Wnt, transforming growth factor beta (TGF beta) and Notch, displayed dynamic changes of their expression during tail regeneration. Notably, this approach enabled us to newly identify seven secreted signaling molecule genes (mdk, fstl, slit1, tgfbeta1, bmp7.1, angptl2 and egfl6) that are highly expressed in tail AEC cells. Among these genes, five (mdk, fstl, slit1, tgfbeta1 and bmp7.1) were also highly expressed in limb AEC cells but the other two (angptl2 and egfl6) are specifically expressed in tail AEC cells. Interestingly, there was no expression of fgf8 in tail WE/AEC cells, whose expression and pivotal role in limb AEC cells have been reported previously. Thus, we identified common and different properties between tail and limb AEC cells.", "classifications": [ { "id": "Nikaido", "label": "Group Nikaido", "parent": "Fujiwara", "type": "group" }, { "id": "Fujiwara", "label": "Team Fujiwara", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Akinori", "last_name": "Okumura", "name": null }, { "creator_type": "author", "first_name": "Tetsutaro", "last_name": "Hayashi", "name": null }, { "creator_type": "author", "first_name": "Masashi", "last_name": "Ebisawa", "name": null }, { "creator_type": "author", "first_name": "Mika", "last_name": "Yoshimura", "name": null }, { "creator_type": "author", "first_name": "Yohei", "last_name": "Sasagawa", "name": null }, { "creator_type": "author", "first_name": "Itoshi", "last_name": "Nikaido", "name": null }, { "creator_type": "author", "first_name": "Yoshihiko", "last_name": "Umesono", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Mochii", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/dgd.12635" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "31713234" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Epithelium", "descriptor_ui": "D004848", "major_topic": false }, { "descriptor": "Flow Cytometry", "descriptor_ui": "D005434", "major_topic": false }, { "descriptor": "Gene Expression Profiling", "descriptor_ui": "D020869", "major_topic": false }, { "descriptor": "Green Fluorescent Proteins", "descriptor_ui": "D049452", "major_topic": false }, { "descriptor": "Sequence Analysis, RNA", "descriptor_ui": "D017423", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Xenopus laevis", "descriptor_ui": "D014982", "major_topic": false }, { "descriptor": "Xenopus Proteins", "descriptor_ui": "D029867", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019 Dec", "date_precision": "unknown", "issue": "9", "normalized_date": null, "pages": "447-456", "proceedings_title": null, "publisher": "", "title": "Development, growth & differentiation", "volume": "61", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "Cell type-specific transcriptome analysis unveils secreted signaling molecule genes expressed in apical epithelial cap during appendage regeneration.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Cholangiocytes are the epithelial cells that line bile ducts, and ductal plate malformation is a developmental anomaly of bile ducts that causes severe congenital biliary disorders. However, because of a lack of specific marker genes, methods for the stepwise differentiation and isolation of human induced pluripotent stem cell (hiPSC)-derived cholangiocyte progenitors at ductal plate stages have not been established. We herein generated an AQP1-GFP reporter hiPSC line and developed a combination treatment with transforming growth factor (TGF) beta2 and epidermal growth factor (EGF) to induce hiPSC-derived hepatoblasts into AQP1(+) cells in vitro. By confirming that the isolated AQP1(+) cells showed similar gene expression patterns to cholangiocyte progenitors at the remodeling ductal plate stage around gestational week (GW) 20, we established a differentiation protocol from hiPSCs through SOX9(+)CK19(+)AQP1(-) ductal plate-like cells into SOX9(+)CK19(+)AQP1(+) remodeling ductal plate-like cells. We further generated 3D bile duct-like structures from the induced ductal plate-like cells. These results suggest that AQP1 is a useful marker for the generation of remodeling ductal plate cells from hiPSCs. Our methods may contribute to elucidating the differentiation mechanisms of ductal plate cells and the pathogenesis of ductal plate malformation.", "classifications": [ { "id": "Yamamoto", "label": "Group Yamamoto", "parent": "Toyoshima", "type": "group" }, { "id": "Toyoshima", "label": "Team Toyoshima", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Satoshi", "last_name": "Matsui", "name": null }, { "creator_type": "author", "first_name": "Miyuki", "last_name": "Ochiai", "name": null }, { "creator_type": "author", "first_name": "Katsutaro", "last_name": "Yasuda", "name": null }, { "creator_type": "author", "first_name": "Shin-Ichi", "last_name": "Mae", "name": null }, { "creator_type": "author", "first_name": "Maki", "last_name": "Kotaka", "name": null }, { "creator_type": "author", "first_name": "Taro", "last_name": "Toyoda", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Osafune", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.scr.2019.101400" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "30735882" } }, "mesh": [ { "descriptor": "Aquaporin 1", "descriptor_ui": "D051398", "major_topic": true }, { "descriptor": "Bile Ducts", "descriptor_ui": "D001652", "major_topic": true }, { "descriptor": "Epithelial Cells", "descriptor_ui": "D004847", "major_topic": true }, { "descriptor": "Green Fluorescent Proteins", "descriptor_ui": "D049452", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Induced Pluripotent Stem Cells", "descriptor_ui": "D057026", "major_topic": true } ], "publication": { "conference_name": null, "date": "2019 Mar", "date_precision": "unknown", "issue": "", "normalized_date": null, "pages": "101400", "proceedings_title": null, "publisher": "", "title": "Stem cell research", "volume": "35", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "Differentiation and isolation of iPSC-derived remodeling ductal plate-like cells by use of an AQP1-GFP reporter human iPSC line.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Reactive oxygen species (ROS) play critical roles in self-renewal division for various stem cell types. However, it remains unclear how ROS signals are integrated with self-renewal machinery. Here, we report that the MAPK14/MAPK7/BCL6B pathway creates a positive feedback loop to drive spermatogonial stem cell (SSC) self-renewal via ROS amplification. The activation of MAPK14 induced MAPK7 phosphorylation in cultured SSCs, and targeted deletion of Mapk14 or Mapk7 resulted in significant SSC deficiency after spermatogonial transplantation. The activation of this signaling pathway not only induced Nox1 but also increased ROS levels. Chemical screening of MAPK7 targets revealed many ROS-dependent spermatogonial transcription factors, of which BCL6B was found to initiate ROS production by increasing Nox1 expression via ETV5-induced nuclear translocation. Because hydrogen peroxide or Nox1 transfection also induced BCL6B nuclear translocation, our results suggest that BCL6B initiates and amplifies ROS signals to activate ROS-dependent spermatogonial transcription factors by forming a positive feedback loop.", "classifications": [ { "id": "Yamamoto", "label": "Group Yamamoto", "parent": "Toyoshima", "type": "group" }, { "id": "Toyoshima", "label": "Team Toyoshima", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Hiroko", "last_name": "Morimoto", "name": null }, { "creator_type": "author", "first_name": "Mito", "last_name": "Kanastu-Shinohara", "name": null }, { "creator_type": "author", "first_name": "Narumi", "last_name": "Ogonuki", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Kamimura", "name": null }, { "creator_type": "author", "first_name": "Atsuo", "last_name": "Ogura", "name": null }, { "creator_type": "author", "first_name": "Chihiro", "last_name": "Yabe-Nishimura", "name": null }, { "creator_type": "author", "first_name": "Yoshifumi", "last_name": "Mori", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Morimoto", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Kinya", "last_name": "Otsu", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Shinohara", "name": null } ], "identifiers": { "doi": { "normalized": "10.26508/lsa.201900374" }, "pmcid": { "normalized": "PMC6448598" }, "pmid": { "normalized": "30940732" } }, "mesh": [ { "descriptor": "Adult Germline Stem Cells", "descriptor_ui": "D000072956", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Benzodiazepinones", "descriptor_ui": "D001570", "major_topic": false }, { "descriptor": "Cell Proliferation", "descriptor_ui": "D049109", "major_topic": false }, { "descriptor": "Cell Self Renewal", "descriptor_ui": "D000066673", "major_topic": false }, { "descriptor": "DNA-Binding Proteins", "descriptor_ui": "D004268", "major_topic": false }, { "descriptor": "Feedback, Physiological", "descriptor_ui": "D025461", "major_topic": false }, { "descriptor": "Gene Knockout Techniques", "descriptor_ui": "D055786", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Inbred DBA", "descriptor_ui": "D008811", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Mitogen-Activated Protein Kinase 14", "descriptor_ui": "D048308", "major_topic": false }, { "descriptor": "Mitogen-Activated Protein Kinase 7", "descriptor_ui": "D048054", "major_topic": false }, { "descriptor": "NADPH Oxidase 1", "descriptor_ui": "D000074624", "major_topic": false }, { "descriptor": "Reactive Oxygen Species", "descriptor_ui": "D017382", "major_topic": false }, { "descriptor": "Real-Time Polymerase Chain Reaction", "descriptor_ui": "D060888", "major_topic": false }, { "descriptor": "Repressor Proteins", "descriptor_ui": "D012097", "major_topic": false }, { "descriptor": "Transcription Factors", "descriptor_ui": "D014157", "major_topic": false }, { "descriptor": "Transfection", "descriptor_ui": "D014162", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019 Apr", "date_precision": "unknown", "issue": "2", "normalized_date": null, "pages": "", "proceedings_title": null, "publisher": "", "title": "Life science alliance", "volume": "2", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "ROS amplification drives mouse spermatogonial stem cell self-renewal.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "In most cases of sporadic colorectal cancers, tumorigenesis is a multistep process, involving genomic alterations in parallel with morphologic changes. In addition, accumulating evidence suggests that the human gut microbiome is linked to the development of colorectal cancer. Here we performed fecal metagenomic and metabolomic studies on samples from a large cohort of 616 participants who underwent colonoscopy to assess taxonomic and functional characteristics of gut microbiota and metabolites. Microbiome and metabolome shifts were apparent in cases of multiple polypoid adenomas and intramucosal carcinomas, in addition to more advanced lesions. We found two distinct patterns of microbiome elevations. First, the relative abundance of Fusobacterium nucleatum spp. was significantly (P < 0.005) elevated continuously from intramucosal carcinoma to more advanced stages. Second, Atopobium parvulum and Actinomyces odontolyticus, which co-occurred in intramucosal carcinomas, were significantly (P < 0.005) increased only in multiple polypoid adenomas and/or intramucosal carcinomas. Metabolome analyses showed that branched-chain amino acids and phenylalanine were significantly (P < 0.005) increased in intramucosal carcinomas and bile acids, including deoxycholate, were significantly (P < 0.005) elevated in multiple polypoid adenomas and/or intramucosal carcinomas. We identified metagenomic and metabolomic markers to discriminate cases of intramucosal carcinoma from the healthy controls. Our large-cohort multi-omics data indicate that shifts in the microbiome and metabolome occur from the very early stages of the development of colorectal cancer, which is of possible etiological and diagnostic importance.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Shinichi", "last_name": "Yachida", "name": null }, { "creator_type": "author", "first_name": "Sayaka", "last_name": "Mizutani", "name": null }, { "creator_type": "author", "first_name": "Hirotsugu", "last_name": "Shiroma", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Shiba", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Nakajima", "name": null }, { "creator_type": "author", "first_name": "Taku", "last_name": "Sakamoto", "name": null }, { "creator_type": "author", "first_name": "Hikaru", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Keigo", "last_name": "Masuda", "name": null }, { "creator_type": "author", "first_name": "Yuichiro", "last_name": "Nishimoto", "name": null }, { "creator_type": "author", "first_name": "Masaru", "last_name": "Kubo", "name": null }, { "creator_type": "author", "first_name": "Fumie", "last_name": "Hosoda", "name": null }, { "creator_type": "author", "first_name": "Hirofumi", "last_name": "Rokutan", "name": null }, { "creator_type": "author", "first_name": "Minori", "last_name": "Matsumoto", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Takamaru", "name": null }, { "creator_type": "author", "first_name": "Masayoshi", "last_name": "Yamada", "name": null }, { "creator_type": "author", "first_name": "Takahisa", "last_name": "Matsuda", "name": null }, { "creator_type": "author", "first_name": "Motoki", "last_name": "Iwasaki", "name": null }, { "creator_type": "author", "first_name": "Taiki", "last_name": "Yamaji", "name": null }, { "creator_type": "author", "first_name": "Tatsuo", "last_name": "Yachida", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Ken", "last_name": "Kurokawa", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Toyoda", "name": null }, { "creator_type": "author", "first_name": "Yoshitoshi", "last_name": "Ogura", "name": null }, { "creator_type": "author", "first_name": "Tetsuya", "last_name": "Hayashi", "name": null }, { "creator_type": "author", "first_name": "Masanori", "last_name": "Hatakeyama", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Nakagama", "name": null }, { "creator_type": "author", "first_name": "Yutaka", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Shinji", "last_name": "Fukuda", "name": null }, { "creator_type": "author", "first_name": "Tatsuhiro", "last_name": "Shibata", "name": null }, { "creator_type": "author", "first_name": "Takuji", "last_name": "Yamada", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41591-019-0458-7" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "31171880" } }, "mesh": [ { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Case-Control Studies", "descriptor_ui": "D016022", "major_topic": false }, { "descriptor": "Colorectal Neoplasms", "descriptor_ui": "D015179", "major_topic": false }, { "descriptor": "Disease Progression", "descriptor_ui": "D018450", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Gastrointestinal Microbiome", "descriptor_ui": "D000069196", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Metabolomics", "descriptor_ui": "D055432", "major_topic": false }, { "descriptor": "Metagenomics", "descriptor_ui": "D056186", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Neoplasm Staging", "descriptor_ui": "D009367", "major_topic": false }, { "descriptor": "Young Adult", "descriptor_ui": "D055815", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019 Jun", "date_precision": "unknown", "issue": "6", "normalized_date": null, "pages": "968-976", "proceedings_title": null, "publisher": "", "title": "Nature medicine", "volume": "25", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "Metagenomic and metabolomic analyses reveal distinct stage-specific phenotypes of the gut microbiota in colorectal cancer.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Histopathology requires the expertise of specialists to diagnose morphological features of cells and tissues. Raman imaging can provide additional biochemical information to benefit histological disease diagnosis. Using a dietary model of nonalcoholic fatty liver disease in rats, we combine Raman imaging with machine learning and information theory to evaluate cellular-level information in liver tissue samples. After increasing signal-to-noise ratio in the Raman images through superpixel segmentation, we extract biochemically distinct regions within liver tissues, allowing for quantification of characteristic biochemical components such as vitamin A and lipids. Armed with microscopic information about the biochemical composition of the liver tissues, we group tissues having similar composition, providing a descriptor enabling inference of tissue states, contributing valuable information to histological inspection.", "classifications": [ { "id": "Fujita", "label": "Group Fujita", "parent": "Fujita", "type": "group" }, { "id": "Tanaka", "label": "Group Tanaka", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Khalifa Mohammad", "last_name": "Helal", "name": null }, { "creator_type": "author", "first_name": "James Nicholas", "last_name": "Taylor", "name": null }, { "creator_type": "author", "first_name": "Harsono", "last_name": "Cahyadi", "name": null }, { "creator_type": "author", "first_name": "Akira", "last_name": "Okajima", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Tabata", "name": null }, { "creator_type": "author", "first_name": "Yoshito", "last_name": "Itoh", "name": null }, { "creator_type": "author", "first_name": "Hideo", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Katsumasa", "last_name": "Fujita", "name": null }, { "creator_type": "author", "first_name": "Yoshinori", "last_name": "Harada", "name": null }, { "creator_type": "author", "first_name": "Tamiki", "last_name": "Komatsuzaki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/1873-3468.13520" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "31254349" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Liver", "descriptor_ui": "D008099", "major_topic": false }, { "descriptor": "Machine Learning", "descriptor_ui": "D000069550", "major_topic": true }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Non-alcoholic Fatty Liver Disease", "descriptor_ui": "D065626", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Rats, Sprague-Dawley", "descriptor_ui": "D017207", "major_topic": false }, { "descriptor": "Signal-To-Noise Ratio", "descriptor_ui": "D059629", "major_topic": false }, { "descriptor": "Spectrum Analysis, Raman", "descriptor_ui": "D013059", "major_topic": true } ], "publication": { "conference_name": null, "date": "2019 Sep", "date_precision": "unknown", "issue": "18", "normalized_date": null, "pages": "2535-2544", "proceedings_title": null, "publisher": "", "title": "FEBS letters", "volume": "593", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "Raman spectroscopic histology using machine learning for nonalcoholic fatty liver disease.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "INTRODUCTION: Disseminated intravascular coagulation (DIC) is a lethal complication in patients with hematologic malignancies (HMs). DIC can be induced by the HM itself, but also by HM-associated secondary infection; however, whether difference of triggering factor impacts the outcome of DIC in HM patients remains unknown. The objective of this study is to clarify the difference between HM-induced DIC and infection-induced DIC in HM patients regarding treatment response and prognosis. METHODS: HM-induced DIC (158 episodes) and infection-induced DIC in HM patients (83 episodes) from a single center were retrospectively analyzed. Recombinant human thrombomodulin (rhTM) was administered in 149 episodes, while the remaining received conventional therapies. RESULTS: In HM-induced DIC, improvement by day 7 was 46% (95% confidence interval [CI], 38-54), and rhTM enhanced the improvement (hazard ratio [HR], 1.7; 95% CI, 1.1-2.4). In contrast, improvement of infection-induced DIC was significantly worse (29%; 95% CI, 20-39 on day 7), and this was not influenced by rhTM (HR, 1.0; 95% CI, 0.50-2.2). Thirty-day survival in HM-induced DIC and infection-induced DIC was 87% (95% CI, 81-92) and 53% (95% CI, 42-63), respectively, and was not affected by treatment. A DIC score (Japanese Ministry of Health and Welfare criteria) of >/=5 was a predictor of worse survival in both types of DIC (HR, 2.5; 95% CI, 1.5-3.9). CONCLUSIONS: This study showed the inadequacy of current therapeutic strategies for secondary infection-induced DIC, the prognosis of which was significantly worse than HM-induced DIC, and the limited efficacy of rhTM only in the improvement of HM-induced DIC.", "classifications": [ { "id": "Nishikii", "label": "Group Nishikii", "parent": "Shintaku", "type": "group" }, { "id": "Shintaku", "label": "Team Shintaku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Naoki", "last_name": "Kurita", "name": null }, { "creator_type": "author", "first_name": "Tatsuhiro", "last_name": "Sakamoto", "name": null }, { "creator_type": "author", "first_name": "Takayasu", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Manabu", "last_name": "Kusakabe", "name": null }, { "creator_type": "author", "first_name": "Yasuhisa", "last_name": "Yokoyama", "name": null }, { "creator_type": "author", "first_name": "Hidekazu", "last_name": "Nishikii", "name": null }, { "creator_type": "author", "first_name": "Mamiko", "last_name": "Sakata-Yanagimoto", "name": null }, { "creator_type": "author", "first_name": "Naoshi", "last_name": "Obara", "name": null }, { "creator_type": "author", "first_name": "Yuichi", "last_name": "Hasegawa", "name": null }, { "creator_type": "author", "first_name": "Shigeru", "last_name": "Chiba", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.thromres.2018.11.014" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "30472436" } }, "mesh": [ { "descriptor": "Adolescent", "descriptor_ui": "D000293", "major_topic": false }, { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Aged, 80 and over", "descriptor_ui": "D000369", "major_topic": false }, { "descriptor": "Disseminated Intravascular Coagulation", "descriptor_ui": "D004211", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Hematologic Neoplasms", "descriptor_ui": "D019337", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Prognosis", "descriptor_ui": "D011379", "major_topic": false }, { "descriptor": "Recombinant Proteins", "descriptor_ui": "D011994", "major_topic": false }, { "descriptor": "Survival Analysis", "descriptor_ui": "D016019", "major_topic": false }, { "descriptor": "Thrombomodulin", "descriptor_ui": "D018180", "major_topic": false }, { "descriptor": "Treatment Outcome", "descriptor_ui": "D016896", "major_topic": false }, { "descriptor": "Young Adult", "descriptor_ui": "D055815", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019 Jan", "date_precision": "unknown", "issue": "", "normalized_date": null, "pages": "57-64", "proceedings_title": null, "publisher": "", "title": "Thrombosis research", "volume": "173", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "The prognosis of disseminated intravascular coagulation associated with hematologic malignancy and its response to recombinant human thrombomodulin.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Chondrosarcoma is the second most common malignant bone tumor. It is characterized by low vascularity and an abundant extracellular matrix, which confer these tumors resistance to chemotherapy and radiotherapy. There are currently no effective treatment options for relapsed or dedifferentiated chondrosarcoma, and new targeted therapies need to be identified. Isocitrate dehydrogenase (IDH) mutations, which are detected in ~50% of chondrosarcoma patients, contribute to malignant transformation by catalyzing the production of 2-hydroxyglutarate (2-HG), a competitive inhibitor of alpha-ketoglutarate-dependent dioxygenases. Mutant IDH inhibitors are therefore potential novel anticancer drugs in IDH mutant tumors. Here, we examined the efficacy of the inhibition of mutant IDH1 as an antitumor approach in chondrosarcoma cells in vitro and in vivo, and investigated the association between the IDH mutation and chondrosarcoma cells. DS-1001b, a novel, orally bioavailable, selective mutant IDH1 inhibitor, impaired the proliferation of chondrosarcoma cells with IDH1 mutations in vitro and in vivo, and decreased 2-HG levels. RNA-seq analysis showed that inhibition of mutant IDH1 promoted chondrocyte differentiation in the conventional chondrosarcoma L835 cell line and caused cell cycle arrest in the dedifferentiated JJ012 cell line. Mutant IDH1-mediated modulation of SOX9 and CDKN1C expression regulated chondrosarcoma tumor progression, and DS-1001b upregulated the expression of these genes via a common mechanism involving the demethylation of H3K9me3. DS-1001b treatment reversed the epigenetic changes caused by aberrant histone modifications. The present data strongly suggest that inhibition of mutant IDH1 is a promising therapeutic approach in chondrosarcoma, particularly for the treatment of relapsed or dedifferentiated chondrosarcoma.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Makoto", "last_name": "Nakagawa", "name": null }, { "creator_type": "author", "first_name": "Fumihiko", "last_name": "Nakatani", "name": null }, { "creator_type": "author", "first_name": "Hironori", "last_name": "Matsunaga", "name": null }, { "creator_type": "author", "first_name": "Takahiko", "last_name": "Seki", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Endo", "name": null }, { "creator_type": "author", "first_name": "Yoko", "last_name": "Ogawara", "name": null }, { "creator_type": "author", "first_name": "Yukino", "last_name": "Machida", "name": null }, { "creator_type": "author", "first_name": "Takuo", "last_name": "Katsumoto", "name": null }, { "creator_type": "author", "first_name": "Kazutsune", "last_name": "Yamagata", "name": null }, { "creator_type": "author", "first_name": "Ayuna", "last_name": "Hattori", "name": null }, { "creator_type": "author", "first_name": "Shuhei", "last_name": "Fujita", "name": null }, { "creator_type": "author", "first_name": "Yukiko", "last_name": "Aikawa", "name": null }, { "creator_type": "author", "first_name": "Takamasa", "last_name": "Ishikawa", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Akira", "last_name": "Kawai", "name": null }, { "creator_type": "author", "first_name": "Hirokazu", "last_name": "Chuman", "name": null }, { "creator_type": "author", "first_name": "Nobuhiko", "last_name": "Yokoyama", "name": null }, { "creator_type": "author", "first_name": "Suguru", "last_name": "Fukushima", "name": null }, { "creator_type": "author", "first_name": "Kenichiro", "last_name": "Yahiro", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Kimura", "name": null }, { "creator_type": "author", "first_name": "Eijiro", "last_name": "Shimada", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Hirose", "name": null }, { "creator_type": "author", "first_name": "Toshifumi", "last_name": "Fujiwara", "name": null }, { "creator_type": "author", "first_name": "Nokitaka", "last_name": "Setsu", "name": null }, { "creator_type": "author", "first_name": "Yoshihiro", "last_name": "Matsumoto", "name": null }, { "creator_type": "author", "first_name": "Yukihide", "last_name": "Iwamoto", "name": null }, { "creator_type": "author", "first_name": "Yasuharu", "last_name": "Nakashima", "name": null }, { "creator_type": "author", "first_name": "Issay", "last_name": "Kitabayashi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41388-019-0929-9" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "31406254" } }, "mesh": [ { "descriptor": "Bone Neoplasms", "descriptor_ui": "D001859", "major_topic": false }, { "descriptor": "Cell Cycle Checkpoints", "descriptor_ui": "D059447", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Cell Proliferation", "descriptor_ui": "D049109", "major_topic": false }, { "descriptor": "Chondrosarcoma", "descriptor_ui": "D002813", "major_topic": false }, { "descriptor": "Enzyme Inhibitors", "descriptor_ui": "D004791", "major_topic": false }, { "descriptor": "Glutarates", "descriptor_ui": "D005977", "major_topic": false }, { "descriptor": "Histone Code", "descriptor_ui": "D042421", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Isocitrate Dehydrogenase", "descriptor_ui": "D007521", "major_topic": false }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": true }, { "descriptor": "SOX9 Transcription Factor", "descriptor_ui": "D055758", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019 Oct", "date_precision": "unknown", "issue": "42", "normalized_date": null, "pages": "6835-6849", "proceedings_title": null, "publisher": "", "title": "Oncogene", "volume": "38", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "Selective inhibition of mutant IDH1 by DS-1001b ameliorates aberrant histone modifications and impairs tumor activity in chondrosarcoma.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "AIMS/INTRODUCTION: Non-alcoholic steatohepatitis (NASH), which occurs in association with insulin resistance and hepatic fat accumulation, is characterized by chronic liver injury and fibrosis. NASH onset and progression is closely related to hepatic inflammation, which is partly regulated by the vagus nerve through the alpha7 nicotinic acetylcholine receptor (alpha7nAchR). Hepatic alpha7nAchR action is impeded in obesity and insulin resistance. In the present study, using alpha7nAchR knockout (alpha7KO) mice, we elucidated the effect of alpha7nAchR deficiency on NASH-related inflammation and fibrosis. MATERIALS AND METHODS: alpha7KO mice were fed an atherogenic high-fat diet (AD) for 32 weeks or methionine/choline-deficient diet (MCD) for 6 weeks, both of which induce NASH. Mice were then examined for the degree of NASH-related inflammation and fibrosis by hepatic gene expression analysis and Sirius red histological staining. RESULTS: Hepatic triglyceride accumulation and elevated plasma transaminase levels were observed in both AD and MCD mice, but the plasma transaminase level increase was higher in alpha7KO mice than in control mice. alpha7KO mice fed an AD showed significant upregulation of the Col1a1 gene encoding alpha-1 type I collagen, which is involved in liver fibrosis, and the Ccl2 gene encoding C-C motif chemokine ligand 2, a pro-inflammatory chemokine; alpha7KO mice fed an MCD had significant upregulation of the Col1a1 gene and the Tnf gene, an inflammatory cytokine. Histological analysis showed that AD and MCD exacerbated liver fibrosis in alpha7KO mice. CONCLUSIONS: The results of this study suggest that alpha7nAchR deficiency exacerbates hepatic inflammation and fibrosis in a diet-induced mouse model of NASH.", "classifications": [ { "id": "Inaba", "label": "Group Inaba", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Kumi", "last_name": "Kimura", "name": null }, { "creator_type": "author", "first_name": "Yuka", "last_name": "Inaba", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Toshiya", "last_name": "Matsukawa", "name": null }, { "creator_type": "author", "first_name": "Michihiro", "last_name": "Matsumoto", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Inoue", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/jdi.12964" }, "pmcid": { "normalized": "PMC6497582" }, "pmid": { "normalized": "30369082" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Choline Deficiency", "descriptor_ui": "D002796", "major_topic": false }, { "descriptor": "Collagen Type I", "descriptor_ui": "D024042", "major_topic": false }, { "descriptor": "Collagen Type I, alpha 1 Chain", "descriptor_ui": "D000090602", "major_topic": false }, { "descriptor": "Cytokines", "descriptor_ui": "D016207", "major_topic": false }, { "descriptor": "Diet, High-Fat", "descriptor_ui": "D059305", "major_topic": false }, { "descriptor": "Disease Models, Animal", "descriptor_ui": "D004195", "major_topic": true }, { "descriptor": "Inflammation", "descriptor_ui": "D007249", "major_topic": false }, { "descriptor": "Liver Cirrhosis", "descriptor_ui": "D008103", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Methionine", "descriptor_ui": "D008715", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Non-alcoholic Fatty Liver Disease", "descriptor_ui": "D065626", "major_topic": false }, { "descriptor": "Receptors, Nicotinic", "descriptor_ui": "D011978", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019 May", "date_precision": "unknown", "issue": "3", "normalized_date": null, "pages": "659-666", "proceedings_title": null, "publisher": "", "title": "Journal of diabetes investigation", "volume": "10", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "Nicotinic alpha-7 acetylcholine receptor deficiency exacerbates hepatic inflammation and fibrosis in a mouse model of non-alcoholic steatohepatitis.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Endophthalmitis due to infection with Enterococcus spp. progresses rapidly and often results in substantial and irreversible vision loss. Given that the frequency of this condition caused by vancomycin-resistant Enterococcus faecalis has been increasing, the development of novel therapeutics is urgently required. We have demonstrated the therapeutic potential of bacteriophage ΦEF24C-P2 in a mouse model of endophthalmitis caused by vancomycin-sensitive (EF24) or vancomycin-resistant (VRE2) strains of E. faecalis Phage ΦEF24C-P2 induced rapid and pronounced bacterial lysis in turbidity reduction assays with EF24, VRE2, and clinical isolates derived from patients with E. faecalis-related postoperative endophthalmitis. Endophthalmitis was induced in mice by injection of EF24 or VRE2 (1 × 10(4) cells) into the vitreous. The number of viable bacteria in the eye increased to >1 × 10(7) CFU, and neutrophil infiltration into the eye was detected as an increase in myeloperoxidase activity at 24 h after infection. A clinical score based on loss of visibility of the fundus as well as the number of viable bacteria and the level of myeloperoxidase activity in the eye were all significantly decreased by intravitreous injection of ΦEF24C-P2 6 h after injection of EF24 or VRE2. Whereas histopathologic analysis revealed massive infiltration of inflammatory cells and retinal detachment in vehicle-treated eyes, the number of these cells was greatly reduced and retinal structural integrity was preserved in phage-treated eyes. Our results thus suggest that intravitreous phage therapy is a potential treatment for endophthalmitis caused by vancomycin-sensitive or -resistant strains of E. faecalis.", "classifications": [ { "id": "Suzuki", "label": "Group Suzuki", "parent": "Takekawa", "type": "group" }, { "id": "Takekawa", "label": "Team Takekawa", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Tatsuma", "last_name": "Kishimoto", "name": null }, { "creator_type": "author", "first_name": "Waka", "last_name": "Ishida", "name": null }, { "creator_type": "author", "first_name": "Ken", "last_name": "Fukuda", "name": null }, { "creator_type": "author", "first_name": "Isana", "last_name": "Nakajima", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Jumpei", "last_name": "Uchiyama", "name": null }, { "creator_type": "author", "first_name": "Shigenobu", "last_name": "Matsuzaki", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Todokoro", "name": null }, { "creator_type": "author", "first_name": "Masanori", "last_name": "Daibata", "name": null }, { "creator_type": "author", "first_name": "Atsuki", "last_name": "Fukushima", "name": null } ], "identifiers": { "doi": { "normalized": "10.1128/aac.01088-19" }, "pmcid": { "normalized": "PMC6811408" }, "pmid": { "normalized": "31451497" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Anti-Bacterial Agents", "descriptor_ui": "D000900", "major_topic": false }, { "descriptor": "Bacteriophages", "descriptor_ui": "D001435", "major_topic": false }, { "descriptor": "Disease Models, Animal", "descriptor_ui": "D004195", "major_topic": false }, { "descriptor": "Endophthalmitis", "descriptor_ui": "D009877", "major_topic": false }, { "descriptor": "Enterococcus faecalis", "descriptor_ui": "D013293", "major_topic": false }, { "descriptor": "Eye Infections, Bacterial", "descriptor_ui": "D015818", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Gram-Positive Bacterial Infections", "descriptor_ui": "D016908", "major_topic": false }, { "descriptor": "Injections", "descriptor_ui": "D007267", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Microbial Sensitivity Tests", "descriptor_ui": "D008826", "major_topic": false }, { "descriptor": "Phage Therapy", "descriptor_ui": "D000071059", "major_topic": false }, { "descriptor": "Vancomycin", "descriptor_ui": "D014640", "major_topic": false }, { "descriptor": "Vancomycin Resistance", "descriptor_ui": "D020713", "major_topic": false } ], "publication": { "conference_name": null, "date": "2019 Nov", "date_precision": "unknown", "issue": "11", "normalized_date": null, "pages": "", "proceedings_title": null, "publisher": "", "title": "Antimicrobial agents and chemotherapy", "volume": "63", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "Therapeutic Effects of Intravitreously Administered Bacteriophage in a Mouse Model of Endophthalmitis Caused by Vancomycin-Sensitive or -Resistant Enterococcus faecalis.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "On the curved surfaces of living and nonliving materials, planar excitable wavefronts frequently exhibit a directional change and subsequently undergo a discontinuous (topological) change; i.e., a series of wavefront dynamics from collision, annihilation to splitting. Theoretical studies have shown that excitable planar stable waves change their topology significantly depending on the initial conditions on flat surfaces, whereas the directional change of the waves occurs based on the geometry of curved surfaces. However, it is not clear if the geometry of curved surfaces induces this topological change. In this study, we first demonstrated that the curved surface geometry induces bending, collision, and splitting of a planar stable wavefront by numerically solving an excitable reaction-diffusion equation on a bell-shaped surface. We determined two necessary conditions for inducing the topological change: the characteristic length of the curved surface (i.e., the height of the bell-shaped structure) should be greater than the width of the wave, and the ratio of the height to the width of the bell shape should be greater than a threshold. As for the geometrical mechanism of the latter, we found that a bifurcation of the geodesics on the curved surface provides the alternative minimal paths of the wavefront, which circumvent the surface region with a high local curvature, thereby resulting in the topological change. These conditions imply that the topological change of the wavefront can be predicted on the basis of the curved surfaces, whose structures are larger than the wave width.", "classifications": [ { "id": "Fujimoto", "label": "Group Fujimoto", "parent": "Ueda", "type": "group" }, { "id": "Ueda", "label": "Team Ueda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Kazuya", "last_name": "Horibe", "name": null }, { "creator_type": "author", "first_name": "Ken-Ichi", "last_name": "Hironaka", "name": null }, { "creator_type": "author", "first_name": "Katsuyoshi", "last_name": "Matsushita", "name": null }, { "creator_type": "author", "first_name": "Koichi", "last_name": "Fujimoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1063/1.5108838" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "31575140" } }, "mesh": [], "publication": { "conference_name": null, "date": "2019 Sep", "date_precision": "unknown", "issue": "9", "normalized_date": null, "pages": "093120", "proceedings_title": null, "publisher": "", "title": "Chaos (Woodbury, N.Y.)", "volume": "29", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "Curved surface geometry-induced topological change of an excitable planar wavefront.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Neuroblastoma is a pediatric malignant tumor arising from the sympathetic nervous system. The patients with high-risk neuroblastomas frequently exhibit amplification and high expression of the MYCN gene, resulting in worse clinical outcomes. Vitamin K3 (VK3) is a synthetic VK-like compound that has been known to have antitumor activity against various types of cancers. In the present study, we have asked whether VK3 and its derivative, VK3-OH, could have the antitumor activity against neuroblastoma-derived cells. Based on our results, VK3-OH strongly inhibited cell proliferation and induced apoptotic cell death compared to VK3. Treatment of MYCN-driven neuroblastoma cells with VK3-OH potentiated tumor suppressor p53 accompanied by downregulation of anti-apoptotic Bcl-2 and Mcl-1. Interestingly, VK3-OH also suppressed the MYCN at mRNA and protein levels. Furthermore, we found downregulation of LIN28B following VK3-OH treatment in MYCN-amplified and overexpressed neuroblastoma cells. Collectively, our current findings strongly suggest that VK3-OH provides a potential therapeutic strategy for patients with MYCN-driven neuroblastomas.", "classifications": [ { "id": "Suzuki", "label": "Group Suzuki", "parent": "Takekawa", "type": "group" }, { "id": "Takekawa", "label": "Team Takekawa", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Yoda", "name": null }, { "creator_type": "author", "first_name": "Toshimitsu", "last_name": "Nakayama", "name": null }, { "creator_type": "author", "first_name": "Motofumi", "last_name": "Miura", "name": null }, { "creator_type": "author", "first_name": "Masaharu", "last_name": "Toriyama", "name": null }, { "creator_type": "author", "first_name": "Shigeyasu", "last_name": "Motohashi", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Suzuki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.bbrep.2019.100701" }, "pmcid": { "normalized": "PMC6895568" }, "pmid": { "normalized": "31844686" } }, "mesh": [], "publication": { "conference_name": null, "date": "2019 Dec", "date_precision": "unknown", "issue": "", "normalized_date": null, "pages": "100701", "proceedings_title": null, "publisher": "", "title": "Biochemistry and biophysics reports", "volume": "20", "year": 2019 }, "ssbd": { "database": [], "repository": [] }, "title": "Vitamin K3 derivative induces apoptotic cell death in neuroblastoma via downregulation of MYCN expression.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND/AIM: The aim of this study was to compare the clinical outcomes of patients treated by local radiotherapy or chemotherapy for oligo-recurrent cervical cancer with prior pelvic irradiation. PATIENTS AND METHODS: Forty-one patients who had received pelvic irradiation for cervical cancer developed oligo-recurrent ( 400). The 5-year overall survival (OS) was significantly better in NLS (96.9%) than in MHS (80.0%); however, no significant difference was observed compared with wild-type KRAS (92.8%) (p= 0.66). The presence of p53 was significantly associated with smoking history (p< 0.01). The 5-year OS for NLS with p53-negative KRAS codon 12-mutated NSCLC (n= 28) was significantly better (96.3%) than that for MHS with both p53-positive and -negative KRAS mutation (p= 0.03 and p< 0.03, respectively). CONCLUSIONS: A non to light smoking habit might contribute to an improvement in prognosis that is equivalent to that of wild-type KRAS, and p53 mutation did not affect survival in smokers harboring KRAS codon 12.", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Hiroaki", "last_name": "Kuroda", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Takaaki", "last_name": "Arimura", "name": null }, { "creator_type": "author", "first_name": "Tetsuya", "last_name": "Mizuno", "name": null }, { "creator_type": "author", "first_name": "Noriaki", "last_name": "Sakakura", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null }, { "creator_type": "author", "first_name": "Yukinori", "last_name": "Sakao", "name": null } ], "identifiers": { "doi": { "normalized": "10.3233/cbm-181483" }, "pmcid": { "normalized": "PMC13078570" }, "pmid": { "normalized": "30223391" } }, "mesh": [ { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Aged, 80 and over", "descriptor_ui": "D000369", "major_topic": false }, { "descriptor": "Biomarkers, Tumor", "descriptor_ui": "D014408", "major_topic": false }, { "descriptor": "Carcinoma, Non-Small-Cell Lung", "descriptor_ui": "D002289", "major_topic": false }, { "descriptor": "Disease-Free Survival", "descriptor_ui": "D018572", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Gene Expression Regulation, Neoplastic", "descriptor_ui": "D015972", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Neoplasm Staging", "descriptor_ui": "D009367", "major_topic": false }, { "descriptor": "Prognosis", "descriptor_ui": "D011379", "major_topic": false }, { "descriptor": "Proto-Oncogene Proteins p21(ras)", "descriptor_ui": "D016283", "major_topic": false }, { "descriptor": "Smoking", "descriptor_ui": "D012907", "major_topic": false }, { "descriptor": "Tumor Suppressor Protein p53", "descriptor_ui": "D016159", "major_topic": false } ], "publication": { "conference_name": null, "date": "2018", "date_precision": "year", "issue": "3", "normalized_date": "2018", "pages": "419-426", "proceedings_title": null, "publisher": "", "title": "Cancer biomarkers : section A of Disease markers", "volume": "23", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "Contribution of smoking habit to the prognosis of stage I KRAS-mutated non-small cell lung cancer.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "APOL1 risk alleles associate with chronic kidney disease in African Americans, but the mechanisms remain to be fully understood. We show that APOL1 risk alleles activate protein kinase R (PKR) in cultured cells and transgenic mice. This effect is preserved when a premature stop codon is introduced to APOL1 risk alleles, suggesting that APOL1 RNA but not protein is required for the effect. Podocyte expression of APOL1 risk allele RNA, but not protein, in transgenic mice induces glomerular injury and proteinuria. Structural analysis of the APOL1 RNA shows that the risk variants possess secondary structure serving as a scaffold for tandem PKR binding and activation. These findings provide a mechanism by which APOL1 variants damage podocytes and suggest novel therapeutic strategies.", "classifications": [ { "id": "Okamoto", "label": "Group Okamoto", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Koji", "last_name": "Okamoto", "name": null }, { "creator_type": "author", "first_name": "Jason W.", "last_name": "Rausch", "name": null }, { "creator_type": "author", "first_name": "Hidefumi", "last_name": "Wakashin", "name": null }, { "creator_type": "author", "first_name": "Yulong", "last_name": "Fu", "name": null }, { "creator_type": "author", "first_name": "Joon-Yong", "last_name": "Chung", "name": null }, { "creator_type": "author", "first_name": "Patrick D.", "last_name": "Dummer", "name": null }, { "creator_type": "author", "first_name": "Myung K.", "last_name": "Shin", "name": null }, { "creator_type": "author", "first_name": "Preeti", "last_name": "Chandra", "name": null }, { "creator_type": "author", "first_name": "Kosuke", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Shashi", "last_name": "Shrivastav", "name": null }, { "creator_type": "author", "first_name": "Avi Z.", "last_name": "Rosenberg", "name": null }, { "creator_type": "author", "first_name": "Stephen M.", "last_name": "Hewitt", "name": null }, { "creator_type": "author", "first_name": "Patricio E.", "last_name": "Ray", "name": null }, { "creator_type": "author", "first_name": "Eisei", "last_name": "Noiri", "name": null }, { "creator_type": "author", "first_name": "Stuart F. J.", "last_name": "Le Grice", "name": null }, { "creator_type": "author", "first_name": "Maarten", "last_name": "Hoek", "name": null }, { "creator_type": "author", "first_name": "Zhe", "last_name": "Han", "name": null }, { "creator_type": "author", "first_name": "Cheryl A.", "last_name": "Winkler", "name": null }, { "creator_type": "author", "first_name": "Jeffrey B.", "last_name": "Kopp", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s42003-018-0188-2" }, "pmcid": { "normalized": "PMC6220249" }, "pmid": { "normalized": "30417125" } }, "mesh": [], "publication": { "conference_name": null, "date": "2018", "date_precision": "year", "issue": "", "normalized_date": "2018", "pages": "188", "proceedings_title": null, "publisher": "", "title": "Communications biology", "volume": "1", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "APOL1 risk allele RNA contributes to renal toxicity by activating protein kinase R.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Moderate exercise has been reported to combat several diseases, including cardiovascular diseases and depressants. However, many patients do not have ability to undergo exercise therapy due to aging and severity of the symptoms. Therefore development of new drugs that can imitate exercise therapy is desired and actually studied worldwide. The heart is one of the physical load-responsive target organs such as skeletal muscles and vascular smooth muscles. The heart can adapt from environmental stress by changing its structure and morphology (i.e., remodeling). Physiological remodeling, caused by exercise or pregnancy, can be defined by compensative and reversible changes to the heart, whereas pathological remodeling can be defined by irreversible changes of the heart, through aberrant calcium ion (Ca(2+)) signaling as well as production of reactive oxygen species (ROS). However, crosstalk between Ca(2+) and ROS remains obscure. In this review we will introduce our recent findings on the functional crosstalk between transient receptor potential canonical (TRPC) 3 and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (Nox) 2 as a novel molecular target to mimic exercise therapy.", "classifications": [ { "id": "Nishida", "label": "Group Nishida", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Sayaka", "last_name": "Oda", "name": null }, { "creator_type": "author", "first_name": "Takuro", "last_name": "Numaga-Tomita", "name": null }, { "creator_type": "author", "first_name": "Motohiro", "last_name": "Nishida", "name": null } ], "identifiers": { "doi": { "normalized": "10.1248/yakushi.18-00091-1" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "30270269" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Calcium Signaling", "descriptor_ui": "D020013", "major_topic": false }, { "descriptor": "Depression", "descriptor_ui": "D003863", "major_topic": false }, { "descriptor": "Disease Models, Animal", "descriptor_ui": "D004195", "major_topic": false }, { "descriptor": "Drug Discovery", "descriptor_ui": "D055808", "major_topic": true }, { "descriptor": "Exercise", "descriptor_ui": "D015444", "major_topic": false }, { "descriptor": "Exercise Therapy", "descriptor_ui": "D005081", "major_topic": false }, { "descriptor": "Heart Failure", "descriptor_ui": "D006333", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Molecular Targeted Therapy", "descriptor_ui": "D058990", "major_topic": false }, { "descriptor": "NADPH Oxidase 2", "descriptor_ui": "D000074662", "major_topic": false }, { "descriptor": "Oxidative Stress", "descriptor_ui": "D018384", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Reactive Oxygen Species", "descriptor_ui": "D017382", "major_topic": true }, { "descriptor": "TRPC Cation Channels", "descriptor_ui": "D050052", "major_topic": false }, { "descriptor": "TRPC6 Cation Channel", "descriptor_ui": "D000074287", "major_topic": false } ], "publication": { "conference_name": null, "date": "2018", "date_precision": "year", "issue": "10", "normalized_date": "2018", "pages": "1257-1262", "proceedings_title": null, "publisher": "", "title": "Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan", "volume": "138", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "[New Strategies for Exercise-Mimetic Medication].", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Background: Although beneficial associations have been reported between moderate alcohol intake and the serum lipid profile, it is unclear whether polymorphisms in alcohol-metabolizing enzymes can modify these associations. Here, we assessed the effects of ADH1B His48Arg (rs1229984), ALDH2 Glu504Lys (rs671), and their combination on these associations. Furthermore, we examined if the findings for ALDH2 could be replicated. Methods: We categorized 889 male participants in the Japan Multi-Institutional Collaborative Cohort (J-MICC) Study into two groups based on presence or absence of minor allele(s) or four groups based on genotype combinations. We performed regression analyses of serum lipid concentrations on alcohol intake, with multivariable adjustment. The replication study was conducted among 2,562 men in the Shizuoka part of the J-MICC Study. Results: The ALDH2 Glu/Lys or Lys/Lys groups showed significant decreases in serum low-density lipoprotein (LDL) cholesterol with increasing alcohol consumption; the coefficient per intake increase of 10 g/day was −2.49 mg/dL (95% confidence interval [CI], −3.85 to −1.13), and a significant interaction with the polymorphism was confirmed (P for interaction = 0.006). This inverse correlation was more evident among the ADH1B His/His + ALDH2 Glu/Lys or Lys/Lys groups (−3.24 mg/dL, 95% CI, −5.03 to −1.45). Serum triglycerides were positively associated with alcohol consumption in the ADH1B His/His group (P for interaction = 0.020). The stronger association between serum LDL cholesterol and alcohol consumption in the ALDH2 Glu/Lys or Lys/Lys groups was replicated. Conclusions: The ALDH2 Glu504Lys polymorphism can modify the association between alcohol intake and serum LDL cholesterol in Japanese men.", "classifications": [ { "id": "Tanaka", "label": "Group Tanaka", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Tae", "last_name": "Sasakabe", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Wakai", "name": null }, { "creator_type": "author", "first_name": "Sayo", "last_name": "Kawai", "name": null }, { "creator_type": "author", "first_name": "Asahi", "last_name": "Hishida", "name": null }, { "creator_type": "author", "first_name": "Mariko", "last_name": "Naito", "name": null }, { "creator_type": "author", "first_name": "Sadao", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Yora", "last_name": "Nindita", "name": null }, { "creator_type": "author", "first_name": "Kokichi", "last_name": "Arisawa", "name": null }, { "creator_type": "author", "first_name": "Yoshikuni", "last_name": "Kita", "name": null }, { "creator_type": "author", "first_name": "Megumi", "last_name": "Hara", "name": null }, { "creator_type": "author", "first_name": "Nagato", "last_name": "Kuriyama", "name": null }, { "creator_type": "author", "first_name": "Akie", "last_name": "Hirata", "name": null }, { "creator_type": "author", "first_name": "Haruo", "last_name": "Mikami", "name": null }, { "creator_type": "author", "first_name": "Isao", "last_name": "Oze", "name": null }, { "creator_type": "author", "first_name": "Michiaki", "last_name": "Kubo", "name": null }, { "creator_type": "author", "first_name": "Hideo", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Nobuyuki", "last_name": "Hamajima", "name": null } ], "identifiers": { "doi": { "normalized": "10.2188/jea.je20160189" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "29176272" } }, "mesh": [ { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Alcohol Dehydrogenase", "descriptor_ui": "D000426", "major_topic": false }, { "descriptor": "Alcohol Drinking", "descriptor_ui": "D000428", "major_topic": false }, { "descriptor": "Aldehyde Dehydrogenase, Mitochondrial", "descriptor_ui": "D000071396", "major_topic": false }, { "descriptor": "Alleles", "descriptor_ui": "D000483", "major_topic": false }, { "descriptor": "Cohort Studies", "descriptor_ui": "D015331", "major_topic": false }, { "descriptor": "Genotype", "descriptor_ui": "D005838", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Japan", "descriptor_ui": "D007564", "major_topic": false }, { "descriptor": "Lipoproteins, LDL", "descriptor_ui": "D008077", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Polymorphism, Genetic", "descriptor_ui": "D011110", "major_topic": false }, { "descriptor": "Triglycerides", "descriptor_ui": "D014280", "major_topic": false } ], "publication": { "conference_name": null, "date": "2018", "date_precision": "year", "issue": "4", "normalized_date": "2018", "pages": "185-193", "proceedings_title": null, "publisher": "", "title": "Journal of Epidemiology", "volume": "28", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "Modification of the Associations of Alcohol Intake With Serum Low-Density Lipoprotein Cholesterol and Triglycerides by ALDH2 and ADH1B Polymorphisms in Japanese Men.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "High-throughput single-cell RNA-seq methods assign limited unique molecular identifier (UMI) counts as gene expression values to single cells from shallow sequence reads and detect limited gene counts. We thus developed a high-throughput single-cell RNA-seq method, Quartz-Seq2, to overcome these issues. Our improvements in the reaction steps make it possible to effectively convert initial reads to UMI counts, at a rate of 30–50%, and detect more genes. To demonstrate the power of Quartz-Seq2, we analyzed approximately 10,000 transcriptomes from in vitro embryonic stem cells and an in vivo stromal vascular fraction with a limited number of reads.Electronic supplementary material: The online version of this article (10.1186/s13059-018-1407-3) contains supplementary material, which is available to authorized users.", "classifications": [ { "id": "Nikaido", "label": "Group Nikaido", "parent": "Fujiwara", "type": "group" }, { "id": "Fujiwara", "label": "Team Fujiwara", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yohei", "last_name": "Sasagawa", "name": null }, { "creator_type": "author", "first_name": "Hiroki", "last_name": "Danno", "name": null }, { "creator_type": "author", "first_name": "Hitomi", "last_name": "Takada", "name": null }, { "creator_type": "author", "first_name": "Masashi", "last_name": "Ebisawa", "name": null }, { "creator_type": "author", "first_name": "Kaori", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Tetsutaro", "last_name": "Hayashi", "name": null }, { "creator_type": "author", "first_name": "Akira", "last_name": "Kurisaki", "name": null }, { "creator_type": "author", "first_name": "Itoshi", "last_name": "Nikaido", "name": null } ], "identifiers": { "doi": { "normalized": "10.1186/s13059-018-1407-3" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "29523163" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Embryonic Stem Cells", "descriptor_ui": "D053595", "major_topic": false }, { "descriptor": "Gene Expression Profiling", "descriptor_ui": "D020869", "major_topic": false }, { "descriptor": "High-Throughput Nucleotide Sequencing", "descriptor_ui": "D059014", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "RNA-Directed DNA Polymerase", "descriptor_ui": "D012194", "major_topic": false }, { "descriptor": "Sequence Analysis, RNA", "descriptor_ui": "D017423", "major_topic": false }, { "descriptor": "Single-Cell Analysis", "descriptor_ui": "D059010", "major_topic": false } ], "publication": { "conference_name": null, "date": "2018", "date_precision": "year", "issue": "", "normalized_date": "2018", "pages": "", "proceedings_title": null, "publisher": "", "title": "Genome Biology", "volume": "19", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "Quartz-Seq2: a high-throughput single-cell RNA-sequencing method that effectively uses limited sequence reads.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Extracellular signal-regulated kinase (ERK) plays a critical role in tissue homeostasis and tumorigenesis. By utilizing live imaging approaches, we recently uncovered ERK activity dynamics in the intestinal epithelium. Notably, we showed that ERK activity dynamics are defined by composite regulation from two distinct upstream receptors, and alteration of their functional balance underlies tumor cell-specific traits. Here, we discuss these findings.", "classifications": [], "creators": [ { "creator_type": "author", "first_name": "Yu", "last_name": "Muta", "name": null }, { "creator_type": "author", "first_name": "Michiyuki", "last_name": "Matsuda", "name": null }, { "creator_type": "author", "first_name": "Masamichi", "last_name": "Imajo", "name": null } ], "identifiers": { "doi": { "normalized": "10.1080/23723556.2018.1506684" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "30263947" } }, "mesh": [], "publication": { "conference_name": null, "date": "2018", "date_precision": "year", "issue": "5", "normalized_date": "2018", "pages": "", "proceedings_title": null, "publisher": "", "title": "Molecular & Cellular Oncology", "volume": "5", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "Dynamic ERK signaling regulation in intestinal tumorigenesis.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Machine learning-based cell classifiers use cell images to automate cell-type discrimination, which is increasingly becoming beneficial in biological studies and biomedical applications. Brightfield or fluorescence images are generally employed as the classifier input variables. We propose to use Raman spectral images and a method to extract features from these spatial patterns and explore the value of this information for cell discrimination. Raman images provide information regarding distribution of chemical compounds of the considered biological entity. Since each spectral wavelength can be used to reconstruct the distribution of a given compound, spectral images provide multiple channels of information, each representing a different pattern, in contrast to brightfield and fluorescence images. Using a dataset of single living cells, we demonstrate that the spatial information can be ranked by a Fisher discriminant score, and that the top-ranked features can accurately classify cell types. This method is compared with the conventional Raman spectral analysis. We also propose to combine the information from whole spectral analyses and selected spatial features and show that this yields higher classification accuracy. This method provides the basis for a novel and systematic analysis of cell-type investigation using Raman spectral imaging, which may benefit several studies and biomedical applications.", "classifications": [ { "id": "Fujita", "label": "Group Fujita", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Arno", "last_name": "Germond", "name": null }, { "creator_type": "author", "first_name": "Taro", "last_name": "Ichimura", "name": null }, { "creator_type": "author", "first_name": "Liang-da", "last_name": "Chiu", "name": null }, { "creator_type": "author", "first_name": "Katsumasa", "last_name": "Fujita", "name": null }, { "creator_type": "author", "first_name": "Tomonobu M.", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Hideaki", "last_name": "Fujita", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41598-018-30276-1" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "30082723" } }, "mesh": [ { "descriptor": "Algorithms", "descriptor_ui": "D000465", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "Machine Learning", "descriptor_ui": "D000069550", "major_topic": true }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Principal Component Analysis", "descriptor_ui": "D025341", "major_topic": false }, { "descriptor": "Spectrum Analysis, Raman", "descriptor_ui": "D013059", "major_topic": false } ], "publication": { "conference_name": null, "date": "2018", "date_precision": "year", "issue": "", "normalized_date": "2018", "pages": "", "proceedings_title": null, "publisher": "", "title": "Scientific Reports", "volume": "8", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "Cell type discrimination based on image features of molecular component distribution.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Insulin plays a central role in glucose homeostasis, and impairment of insulin action causes glucose intolerance and leads to type 2 diabetes mellitus (T2DM). A decrease in the transient peak and sustained increase of circulating insulin following an infusion of glucose accompany T2DM pathogenesis. However, the mechanism underlying this abnormal temporal pattern of circulating insulin concentration remains unknown. Here we show that changes in opposite direction of hepatic and peripheral insulin clearance characterize this abnormal temporal pattern of circulating insulin concentration observed in T2DM. We developed a mathematical model using a hyperglycemic and hyperinsulinemic-euglycemic clamp in 111 subjects, including healthy normoglycemic and diabetic subjects. The hepatic and peripheral insulin clearance significantly increase and decrease, respectively, from healthy to borderline type and T2DM. The increased hepatic insulin clearance reduces the amplitude of circulating insulin concentration, whereas the decreased peripheral insulin clearance changes the temporal patterns of circulating insulin concentration from transient to sustained. These results provide further insight into the pathogenesis of T2DM, and thus may contribute to develop better treatment of this condition.", "classifications": [ { "id": "Kuroda", "label": "Group Kuroda", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Kaoru", "last_name": "Ohashi", "name": null }, { "creator_type": "author", "first_name": "Masashi", "last_name": "Fujii", "name": null }, { "creator_type": "author", "first_name": "Shinsuke", "last_name": "Uda", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Kubota", "name": null }, { "creator_type": "author", "first_name": "Hisako", "last_name": "Komada", "name": null }, { "creator_type": "author", "first_name": "Kazuhiko", "last_name": "Sakaguchi", "name": null }, { "creator_type": "author", "first_name": "Wataru", "last_name": "Ogawa", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Kuroda", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41540-018-0051-6" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "29560274" } }, "mesh": [], "publication": { "conference_name": null, "date": "2018", "date_precision": "year", "issue": "", "normalized_date": "2018", "pages": "", "proceedings_title": null, "publisher": "", "title": "NPJ Systems Biology and Applications", "volume": "4", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "Increase in hepatic and decrease in peripheral insulin clearance characterize abnormal temporal patterns of serum insulin in diabetic subjects.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Autophagy is a lysosomal degradation system by which cytosolic materials and damaged organelles are broken down into basic components. To explore the physiological role of autophagy in glomerular endothelial cells (GEnCs), we compared the autophagic flux among cells in the kidney under starvation. Inhibition of autophagy by chloroquine administration significantly increased the number of autophagosomes or autolysosomes in GEnCs and proximal tubular cells, but not in podocytes, suggesting that the GEnCs exhibit substantial autophagic activity. Next, we analyzed endothelial and hematopoietic cell-specific atg5-deficient mice (atg5-conditional KO [cKO] mice). Glomeruli of 4-wk-old atg5-cKO mice exhibited slightly distended capillary loops accompanied by an accumulation of reactive oxygen species (ROS). Glomeruli of 8-wk-old atg5-cKO mice showed a lobular pattern with thickening of the capillary loops and mesangial matrix expansion; however, the vasculature of other organs was preserved. The atg5-cKO mice died by 12 wk of age, presumably due to pancytopenia resulting from the defect in their hematopoietic lineages. Therefore, we subjected 4-wk atg5-cKO mice to irradiation followed by bone marrow transplantation from normal littermates. Transplanted mice recapitulated the glomerular phenotypes of the atg5-cKO mice with no obvious histological changes in other organs. Twelve-mo-old transplanted mice developed mesangiolysis and glomerulosclerosis with significant deterioration of kidney function. Administration of N-acetyl-l-cysteine, a ROS scavenger, to atg5-cKO mice rescued the glomerular phenotypes. These data suggest that endothelial autophagy protects glomeruli from oxidative stress and maintains the integrity of glomerular capillaries. Enhancing endothelial autophagy may provide a novel therapeutic approach to minimizing glomerular diseases.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Jun", "last_name": "Matsuda", "name": null }, { "creator_type": "author", "first_name": "Tomoko", "last_name": "Namba", "name": null }, { "creator_type": "author", "first_name": "Yoshitsugu", "last_name": "Takabatake", "name": null }, { "creator_type": "author", "first_name": "Tomonori", "last_name": "Kimura", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Minami", "name": null }, { "creator_type": "author", "first_name": "Shinsuke", "last_name": "Sakai", "name": null }, { "creator_type": "author", "first_name": "Ryuta", "last_name": "Fujimura", "name": null }, { "creator_type": "author", "first_name": "Jun-Ya", "last_name": "Kaimori", "name": null }, { "creator_type": "author", "first_name": "Isao", "last_name": "Matsui", "name": null }, { "creator_type": "author", "first_name": "Takayuki", "last_name": "Hamano", "name": null }, { "creator_type": "author", "first_name": "Yoko", "last_name": "Fukushima", "name": null }, { "creator_type": "author", "first_name": "Keiko", "last_name": "Matsui", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Yoshitaka", "last_name": "Isaka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1080/15548627.2017.1391428" }, "pmcid": { "normalized": "PMC5846506" }, "pmid": { "normalized": "29130363" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Antioxidants", "descriptor_ui": "D000975", "major_topic": false }, { "descriptor": "Autophagy", "descriptor_ui": "D001343", "major_topic": false }, { "descriptor": "Autophagy-Related Protein 5", "descriptor_ui": "D000071187", "major_topic": false }, { "descriptor": "Capillaries", "descriptor_ui": "D002196", "major_topic": false }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Chloroquine", "descriptor_ui": "D002738", "major_topic": false }, { "descriptor": "Endothelial Cells", "descriptor_ui": "D042783", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Kidney Diseases", "descriptor_ui": "D007674", "major_topic": false }, { "descriptor": "Kidney Glomerulus", "descriptor_ui": "D007678", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Oxidative Stress", "descriptor_ui": "D018384", "major_topic": false }, { "descriptor": "Reactive Oxygen Species", "descriptor_ui": "D017382", "major_topic": false } ], "publication": { "conference_name": null, "date": "2018", "date_precision": "year", "issue": "1", "normalized_date": "2018", "pages": "53-65", "proceedings_title": null, "publisher": "", "title": "Autophagy", "volume": "14", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "Antioxidant role of autophagy in maintaining the integrity of glomerular capillaries.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Coffee is one of the most widely consumed beverages worldwide, and its role in human health has received much attention. Although genome-wide association studies (GWASs) have investigated genetic variants associated with coffee consumption in European populations, no such study has yet been conducted in an Asian population. Here, we conducted a GWAS to identify common genetic variations that affected coffee consumption in a Japanese population of 11,261 participants recruited as a part of the Japan Multi-Institutional Collaborative Cohort (J-MICC) study. Coffee consumption was collected using a self-administered questionnaire, and converted from categories to cups/day. In the discovery stage (n = 6,312), we found 2 independent loci (12q24.12–13 and 5q33.3) that met suggestive significance (P < 1 × 10−6). In the replication stage (n = 4,949), the lead variant for the 12q24.12–13 locus (rs2074356) was significantly associated with habitual coffee consumption (P = 2.2 × 10−6), whereas the lead variant for the 5q33.3 locus (rs1957553) was not (P = 0.53). A meta-analysis of the discovery and replication populations, and the combined analysis using all subjects, revealed that rs2074356 achieved genome-wide significance (P = 2.2 × 10−16 for a meta-analysis). These findings indicate that the 12q24.12-13 locus is associated with coffee consumption among a Japanese population.", "classifications": [ { "id": "Tanaka", "label": "Group Tanaka", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Hiroko", "last_name": "Nakagawa-Senda", "name": null }, { "creator_type": "author", "first_name": "Tsuyoshi", "last_name": "Hachiya", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Shimizu", "name": null }, { "creator_type": "author", "first_name": "Satoyo", "last_name": "Hosono", "name": null }, { "creator_type": "author", "first_name": "Isao", "last_name": "Oze", "name": null }, { "creator_type": "author", "first_name": "Miki", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Keitaro", "last_name": "Matsuo", "name": null }, { "creator_type": "author", "first_name": "Hidemi", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Megumi", "last_name": "Hara", "name": null }, { "creator_type": "author", "first_name": "Yuichiro", "last_name": "Nishida", "name": null }, { "creator_type": "author", "first_name": "Kaori", "last_name": "Endoh", "name": null }, { "creator_type": "author", "first_name": "Kiyonori", "last_name": "Kuriki", "name": null }, { "creator_type": "author", "first_name": "Sakurako", "last_name": "Katsuura-Kamano", "name": null }, { "creator_type": "author", "first_name": "Kokichi", "last_name": "Arisawa", "name": null }, { "creator_type": "author", "first_name": "Yora", "last_name": "Nindita", "name": null }, { "creator_type": "author", "first_name": "Rie", "last_name": "Ibusuki", "name": null }, { "creator_type": "author", "first_name": "Sadao", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Akihiro", "last_name": "Hosono", "name": null }, { "creator_type": "author", "first_name": "Haruo", "last_name": "Mikami", "name": null }, { "creator_type": "author", "first_name": "Yohko", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Naoyuki", "last_name": "Takashima", "name": null }, { "creator_type": "author", "first_name": "Yasuyuki", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Nagato", "last_name": "Kuriyama", "name": null }, { "creator_type": "author", "first_name": "Etsuko", "last_name": "Ozaki", "name": null }, { "creator_type": "author", "first_name": "Norihiro", "last_name": "Furusyo", "name": null }, { "creator_type": "author", "first_name": "Hiroaki", "last_name": "Ikezaki", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Nakatochi", "name": null }, { "creator_type": "author", "first_name": "Tae", "last_name": "Sasakabe", "name": null }, { "creator_type": "author", "first_name": "Sayo", "last_name": "Kawai", "name": null }, { "creator_type": "author", "first_name": "Rieko", "last_name": "Okada", "name": null }, { "creator_type": "author", "first_name": "Asahi", "last_name": "Hishida", "name": null }, { "creator_type": "author", "first_name": "Mariko", "last_name": "Naito", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Wakai", "name": null }, { "creator_type": "author", "first_name": "Yukihide", "last_name": "Momozawa", "name": null }, { "creator_type": "author", "first_name": "Michiaki", "last_name": "Kubo", "name": null }, { "creator_type": "author", "first_name": "Hideo", "last_name": "Tanaka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41598-018-19914-w" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "29367735" } }, "mesh": [ { "descriptor": "Asian People", "descriptor_ui": "D044466", "major_topic": false }, { "descriptor": "Chromosomes, Human, Pair 12", "descriptor_ui": "D002881", "major_topic": false }, { "descriptor": "Coffee", "descriptor_ui": "D003069", "major_topic": false }, { "descriptor": "Cohort Studies", "descriptor_ui": "D015331", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Gene Expression Regulation", "descriptor_ui": "D005786", "major_topic": false }, { "descriptor": "Genome-Wide Association Study", "descriptor_ui": "D055106", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Polymorphism, Single Nucleotide", "descriptor_ui": "D020641", "major_topic": true }, { "descriptor": "Risk Factors", "descriptor_ui": "D012307", "major_topic": false }, { "descriptor": "Surveys and Questionnaires", "descriptor_ui": "D011795", "major_topic": false } ], "publication": { "conference_name": null, "date": "2018", "date_precision": "year", "issue": "", "normalized_date": "2018", "pages": "", "proceedings_title": null, "publisher": "", "title": "Scientific Reports", "volume": "8", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "A genome-wide association study in the Japanese population identifies the 12q24 locus for habitual coffee consumption: The J-MICC Study.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "We report the case of a 76-year-old man who was diagnosed as having chronic myeloid leukemia (CML) with p190 BCR-ABL while receiving treatment for symptomatic multiple myeloma (MM). The diagnosis of MM was based on the presence of serum M-protein, abnormal plasma cells in the bone marrow, and lytic bone lesions. The patient achieved a partial response to lenalidomide and dexamethasone treatment. However, 2 years after the diagnosis of MM, the patient developed leukocytosis with granulocytosis, anemia, and thrombocytopenia. Bone marrow examination revealed Philadelphia chromosomes and chimeric p190 BCR-ABL mRNA. Fluorescence in situ hybridization also revealed BCR-ABL-positive neutrophils in the peripheral blood, which suggested the emergence of CML with p190 BCR-ABL. The codevelopment of MM and CML is very rare, and this is the first report describing p190 BCR-ABL-type CML coexisting with MM. Moreover, we have reviewed the literature regarding the coexistence of these diseases.", "classifications": [ { "id": "Nishikii", "label": "Group Nishikii", "parent": "Shintaku", "type": "group" }, { "id": "Shintaku", "label": "Team Shintaku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Kosuke", "last_name": "Miki", "name": null }, { "creator_type": "author", "first_name": "Naoshi", "last_name": "Obara", "name": null }, { "creator_type": "author", "first_name": "Kenichi", "last_name": "Makishima", "name": null }, { "creator_type": "author", "first_name": "Tatsuhiro", "last_name": "Sakamoto", "name": null }, { "creator_type": "author", "first_name": "Manabu", "last_name": "Kusakabe", "name": null }, { "creator_type": "author", "first_name": "Takayasu", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Naoki", "last_name": "Kurita", "name": null }, { "creator_type": "author", "first_name": "Hidekazu", "last_name": "Nishikii", "name": null }, { "creator_type": "author", "first_name": "Yasuhisa", "last_name": "Yokoyama", "name": null }, { "creator_type": "author", "first_name": "Mamiko", "last_name": "Sakata-Yanagimoto", "name": null }, { "creator_type": "author", "first_name": "Yuichi", "last_name": "Hasegawa", "name": null }, { "creator_type": "author", "first_name": "Shigeru", "last_name": "Chiba", "name": null } ], "identifiers": { "doi": { "normalized": "10.1155/2018/7863943" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "30405922" } }, "mesh": [], "publication": { "conference_name": null, "date": "2018", "date_precision": "year", "issue": "", "normalized_date": "2018", "pages": "", "proceedings_title": null, "publisher": "", "title": "Case Reports in Hematology", "volume": "2018", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "An Unprecedented Case of p190 BCR-ABL Chronic Myeloid Leukemia Diagnosed during Treatment for Multiple Myeloma: A Case Report and Review of the Literature.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Background: Increasing evidence regarding the neural correlates of excessive or pathological internet use (IU) has accumulated in recent years, and comorbidity with depression and autism has been reported in multiple studies. However, psychological and neural correlates of non-clinical IU in healthy individuals remain unclear. Objectives: The aim of the current study was to investigate the relationships between non-clinical IU and functional connectivity (FC), focusing on the brain's motivation network. We sought to clarify the influence of depression and autistic traits on these relationships in healthy individuals. Methods: Resting-state functional magnetic resonance imaging (fMRI) was performed in 119 healthy volunteers. IU, depression, and autistic traits were assessed using the Generalized Problematic Internet Use Scale 2 (GPIUS2), Beck Depression Inventory-II (BDI-II), and the autism spectrum quotient (AQ) scale, respectively. Correlational analyses were performed using CONN-software within the motivation-related network, which consisted of 22 brain regions defined by a previous response-conflict task-based fMRI study with a reward cue. We also performed mediation analyses via the bootstrap method. Results: Total GPIUS2 scores were positively correlated with FC between the (a) left middle frontal gyrus (MFG) and bilateral medial prefrontal cortex; (b) left MFG and right supplementary motor area (SMA); (c) left MFG and right anterior insula, and (d) right MFG and right insula. The \"Mood Regulation\" subscale of the GPIUS2 was positively correlated with FC between left MFG and right SMA. The \"Deficient Self-Regulation\" subscale was positively correlated with FC between right MFG and right anterior insula (statistical thresholds, FDR < 0.05). Among these significant correlations, those between GPIUS2 (total and \"Mood Regulation\" subscale) scores and FC became stronger after controlling for AQ scores (total and \"Attention Switching\" subscale), indicating significant mediation by AQ (95% CI < 0.05). In contrast, BDI-II had no mediating effect. Conclusion: Positive correlations between IU and FC in the motivation network may indicate health-promoting effects of non-clinical IU. However, this favorable association is attenuated in individuals with subclinical autistic traits, suggesting the importance of a personalized educational approach for these individuals in terms of adequate IU.", "classifications": [ { "id": "Fujiwara", "label": "Group Fujiwara", "parent": "Fujiwara", "type": "group" }, { "id": "Fujiwara", "label": "Team Fujiwara", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Hironobu", "last_name": "Fujiwara", "name": null }, { "creator_type": "author", "first_name": "Sayaka", "last_name": "Yoshimura", "name": null }, { "creator_type": "author", "first_name": "Kei", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Tsukasa", "last_name": "Ueno", "name": null }, { "creator_type": "author", "first_name": "Naoya", "last_name": "Oishi", "name": null }, { "creator_type": "author", "first_name": "Toshiya", "last_name": "Murai", "name": null } ], "identifiers": { "doi": { "normalized": "10.3389/fnhum.2018.00493" }, "pmcid": { "normalized": "PMC6295452" }, "pmid": { "normalized": "30618678" } }, "mesh": [], "publication": { "conference_name": null, "date": "2018", "date_precision": "year", "issue": "", "normalized_date": "2018", "pages": "493", "proceedings_title": null, "publisher": "", "title": "Frontiers in human neuroscience", "volume": "12", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "Neural Correlates of Non-clinical Internet Use in the Motivation Network and Its Modulation by Subclinical Autistic Traits.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Cardiac hypertrophy, induced by neurohumoral factors, including angiotensin II and endothelin-1, is a major predisposing factor for heart failure. These ligands can induce hypertrophic growth of neonatal rat cardiomyocytes (NRCMs) mainly through Ca2+-dependent calcineurin/nuclear factor of activated T cell (NFAT) signaling pathways activated by diacylglycerol-activated transient receptor potential canonical 3 and 6 (TRPC3/6) heteromultimer channels. Although extracellular nucleotide, adenosine 5′-triphosphate (ATP), is also known as most potent Ca2+-mobilizing ligand that acts on purinergic receptors, ATP never induces cardiomyocyte hypertrophy. Here we show that ATP-induced production of nitric oxide (NO) negatively regulates hypertrophic signaling mediated by TRPC3/6 channels in NRCMs. Pharmacological inhibition of NO synthase (NOS) potentiated ATP-induced increases in NFAT activity, protein synthesis, and transcriptional activity of brain natriuretic peptide. ATP significantly increased NO production and protein kinase G (PKG) activity compared to angiotensin II and endothelin-1. We found that ATP-induced Ca2+ signaling requires inositol 1,4,5-trisphosphate (IP3) receptor activation. Interestingly, inhibition of TRPC5, but not TRPC6 attenuated ATP-induced activation of Ca2+/NFAT-dependent signaling. As inhibition of TRPC5 attenuates ATP-stimulated NOS activation, these results suggest that NO-cGMP-PKG axis activated by IP3-mediated TRPC5 channels underlies negative regulation of TRPC3/6-dependent hypertrophic signaling induced by ATP stimulation.", "classifications": [ { "id": "Nishida", "label": "Group Nishida", "parent": "Nishida", "type": "group" }, { "id": "Nishimura", "label": "Group Nishimura", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Caroline", "last_name": "Sunggip", "name": null }, { "creator_type": "author", "first_name": "Kakeru", "last_name": "Shimoda", "name": null }, { "creator_type": "author", "first_name": "Sayaka", "last_name": "Oda", "name": null }, { "creator_type": "author", "first_name": "Tomohiro", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Kazuhiro", "last_name": "Nishiyama", "name": null }, { "creator_type": "author", "first_name": "Supachoke", "last_name": "Mangmool", "name": null }, { "creator_type": "author", "first_name": "Akiyuki", "last_name": "Nishimura", "name": null }, { "creator_type": "author", "first_name": "Takuro", "last_name": "Numaga-Tomita", "name": null }, { "creator_type": "author", "first_name": "Motohiro", "last_name": "Nishida", "name": null } ], "identifiers": { "doi": { "normalized": "10.3389/fphar.2018.00523" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "29872396" } }, "mesh": [], "publication": { "conference_name": null, "date": "2018", "date_precision": "year", "issue": "", "normalized_date": "2018", "pages": "", "proceedings_title": null, "publisher": "", "title": "Frontiers in Pharmacology", "volume": "9", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "TRPC5-eNOS Axis Negatively Regulates ATP-Induced Cardiomyocyte Hypertrophy.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The consumption of soybean protein has well-known favorable metabolic effects (e.g., reduced body weight, body fat, hyperglycemia, insulin resistance, hepatic steatosis, and lipogenesis). These effects of soy protein have been linked to modulation by the gut microbiota; however, the dynamic interplay among these factors remains unclear. Accordingly, we examined the metabolic phenotype, intestinal BA pool, and the gut microbiome of male C57BL/6 mice that were randomized to receive either a regular high-fat diet (HFD) or HFD that contained soybean protein isolate (SPI) in place of dairy protein. The intake of SPI significantly reduced the HFD-induced weight gain and adipose tissue mass accumulation and attenuated hepatic steatosis. Along with an enhancement in the secretion of intestinal Glucagon-like peptide-1 (GLP-1), an enlarged cecal BA pool with an elevated secondary/primary BA ratio was observed in the mice that consumed SPI, while fecal BA excretion remained unaltered. SPI also elicited dramatic changes in the gut microbiome, characterized by an expansion of taxa that may be involved in the biotransformation of BAs. The observed effects were abolished in germ-free (GF) mice, indicating that they were dependent on the microbiota. These findings collectively indicate that the metabolic benefits of SPI under the HFD regime may arise from a microbiota-driven increase in BA transformation and increase in GLP-1 secretion.", "classifications": [ { "id": "Inaba", "label": "Group Inaba", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Keita", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Miki", "last_name": "Igarashi", "name": null }, { "creator_type": "author", "first_name": "Xuan", "last_name": "Li", "name": null }, { "creator_type": "author", "first_name": "Akiho", "last_name": "Nakatani", "name": null }, { "creator_type": "author", "first_name": "Junki", "last_name": "Miyamoto", "name": null }, { "creator_type": "author", "first_name": "Yuka", "last_name": "Inaba", "name": null }, { "creator_type": "author", "first_name": "Asuka", "last_name": "Sutou", "name": null }, { "creator_type": "author", "first_name": "Tsutomu", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Takumi", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Nobuhiko", "last_name": "Tachibana", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Inoue", "name": null }, { "creator_type": "author", "first_name": "Ikuo", "last_name": "Kimura", "name": null } ], "identifiers": { "doi": { "normalized": "10.1371/journal.pone.0202083" }, "pmcid": { "normalized": "PMC6089412" }, "pmid": { "normalized": "30102711" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Bile Acids and Salts", "descriptor_ui": "D001647", "major_topic": false }, { "descriptor": "Biodiversity", "descriptor_ui": "D044822", "major_topic": false }, { "descriptor": "Diet, High-Fat", "descriptor_ui": "D059305", "major_topic": false }, { "descriptor": "Dietary Supplements", "descriptor_ui": "D019587", "major_topic": false }, { "descriptor": "Gastrointestinal Microbiome", "descriptor_ui": "D000069196", "major_topic": false }, { "descriptor": "Glucagon-Like Peptide 1", "descriptor_ui": "D052216", "major_topic": false }, { "descriptor": "Intestinal Mucosa", "descriptor_ui": "D007413", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Metabolic Networks and Pathways", "descriptor_ui": "D053858", "major_topic": false }, { "descriptor": "Metagenome", "descriptor_ui": "D054892", "major_topic": false }, { "descriptor": "Metagenomics", "descriptor_ui": "D056186", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Obesity", "descriptor_ui": "D009765", "major_topic": false }, { "descriptor": "Soybean Proteins", "descriptor_ui": "D030262", "major_topic": false } ], "publication": { "conference_name": null, "date": "2018", "date_precision": "year", "issue": "8", "normalized_date": "2018", "pages": "e0202083", "proceedings_title": null, "publisher": "", "title": "PloS one", "volume": "13", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "Dietary soybean protein ameliorates high-fat diet-induced obesity by modifying the gut microbiota-dependent biotransformation of bile acids.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Total RNA sequencing has been used to reveal poly(A) and non-poly(A) RNA expression, RNA processing and enhancer activity. To date, no method for full-length total RNA sequencing of single cells has been developed despite the potential of this technology for single-cell biology. Here we describe random displacement amplification sequencing (RamDA-seq), the first full-length total RNA-sequencing method for single cells. Compared with other methods, RamDA-seq shows high sensitivity to non-poly(A) RNA and near-complete full-length transcript coverage. Using RamDA-seq with differentiation time course samples of mouse embryonic stem cells, we reveal hundreds of dynamically regulated non-poly(A) transcripts, including histone transcripts and long noncoding RNA Neat1. Moreover, RamDA-seq profiles recursive splicing in >300-kb introns. RamDA-seq also detects enhancer RNAs and their cell type-specific activity in single cells. Taken together, we demonstrate that RamDA-seq could help investigate the dynamics of gene expression, RNA-processing events and transcriptional regulation in single cells.", "classifications": [ { "id": "Nikaido", "label": "Group Nikaido", "parent": "Fujiwara", "type": "group" }, { "id": "Fujiwara", "label": "Team Fujiwara", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Tetsutaro", "last_name": "Hayashi", "name": null }, { "creator_type": "author", "first_name": "Haruka", "last_name": "Ozaki", "name": null }, { "creator_type": "author", "first_name": "Yohei", "last_name": "Sasagawa", "name": null }, { "creator_type": "author", "first_name": "Mana", "last_name": "Umeda", "name": null }, { "creator_type": "author", "first_name": "Hiroki", "last_name": "Danno", "name": null }, { "creator_type": "author", "first_name": "Itoshi", "last_name": "Nikaido", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41467-018-02866-0" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "29434199" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Base Sequence", "descriptor_ui": "D001483", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Enhancer Elements, Genetic", "descriptor_ui": "D004742", "major_topic": false }, { "descriptor": "Exons", "descriptor_ui": "D005091", "major_topic": false }, { "descriptor": "High-Throughput Nucleotide Sequencing", "descriptor_ui": "D059014", "major_topic": false }, { "descriptor": "Histones", "descriptor_ui": "D006657", "major_topic": false }, { "descriptor": "Introns", "descriptor_ui": "D007438", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mouse Embryonic Stem Cells", "descriptor_ui": "D000066450", "major_topic": false }, { "descriptor": "RNA Splicing", "descriptor_ui": "D012326", "major_topic": true }, { "descriptor": "RNA, Long Noncoding", "descriptor_ui": "D062085", "major_topic": false }, { "descriptor": "RNA, Messenger", "descriptor_ui": "D012333", "major_topic": false }, { "descriptor": "Sequence Analysis, RNA", "descriptor_ui": "D017423", "major_topic": false }, { "descriptor": "Single-Cell Analysis", "descriptor_ui": "D059010", "major_topic": false }, { "descriptor": "Transcription, Genetic", "descriptor_ui": "D014158", "major_topic": false } ], "publication": { "conference_name": null, "date": "2018", "date_precision": "year", "issue": "", "normalized_date": "2018", "pages": "", "proceedings_title": null, "publisher": "", "title": "Nature Communications", "volume": "9", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "Single-cell full-length total RNA sequencing uncovers dynamics of recursive splicing and enhancer RNAs.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "We describe further potential of generalized 2D correlation analysis, aiming to realize the automation of the sequential order determination of signal variations. By modeling unimodal waveforms using quadratic functions, we can analytically express 2D correlation functions to yield an index to determine the sequential order. Based on the obtained results, we find an exception for determining the sequential order of signal variations. To resolve the exception, we suggest an extended way of interpreting the sequential order of signal intensity changes.", "classifications": [ { "id": "Nakabayashi", "label": "Group Nakabayashi", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Tatsuro", "last_name": "Sugawara", "name": null }, { "creator_type": "author", "first_name": "Takakazu", "last_name": "Nakabayashi", "name": null }, { "creator_type": "author", "first_name": "Shin-Ichi", "last_name": "Morita", "name": null } ], "identifiers": { "doi": { "normalized": "10.2116/analsci.17n040" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "29998969" } }, "mesh": [], "publication": { "conference_name": null, "date": "2018", "date_precision": "year", "issue": "7", "normalized_date": "2018", "pages": "845-847", "proceedings_title": null, "publisher": "", "title": "Analytical sciences : the international journal of the Japan Society for Analytical Chemistry", "volume": "34", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "Generalized Two-dimensional Correlation Analysis for Unimodal Waveforms Modeled by Quadratic Polynomials.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "", "classifications": [ { "id": "Onami", "label": "Group Onami", "parent": "Fujiwara", "type": "group" }, { "id": "Fujiwara", "label": "Team Fujiwara", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Momoko", "last_name": "Imakubo", "name": null }, { "creator_type": "author", "first_name": "Jun", "last_name": "Takayama", "name": null }, { "creator_type": "author", "first_name": "Shuichi", "last_name": "Onami", "name": null } ], "identifiers": { "doi": { "normalized": "10.2197/ipsjtbio.11.24" }, "pmcid": { "normalized": null }, "pmid": { "normalized": null } }, "mesh": [], "publication": { "conference_name": null, "date": "2018", "date_precision": "year", "issue": "", "normalized_date": "2018", "pages": "24-30", "proceedings_title": null, "publisher": "", "title": "IPSJ Transactions on Bioinformatics", "volume": "11", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "Improvement and Evaluation of a Mathematical Model for Fertilization Calcium Waves in Caenorhabditis Elegans", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The hyaluronic acid component of the glycocalyx plays a role in cell mechanotransduction by selectively transmitting mechanical signals to the cell cytoskeleton or to the cell membrane. The aim of this study was to evaluate the mechanical link between the hyaluronic acid molecule and the cell cytoskeleton by means of atomic force microscopy single molecule force spectroscopy. Hyaluronic acid molecules on live cells were targeted with probes coated with hyaluronic acid binding protein. Two different types of events were observed when the detachment of the target molecule from the probe occurred, suggesting the presence of cytoskeleton- and membrane-anchored molecules. Membrane-anchored molecules facilitated the formation of tethers when pulled. About 15% of the tested hyaluronic acid molecules were shown to be anchored to the cytoskeleton. When multiple molecules bonded to the probe, specific detachment patterns were observed, suggesting that a cytoskeletal bond needed to be broken to improve the ability to pull tethers from the cell membrane. This likely resulted in the formation of tethering structures maintaining a cytoskeletal core similar to the ones observed for cells over-expressing HA synthases. The different observed rupture events were associated with separate mechanotransductive mechanisms in an analogous manner to that previously proposed for the endothelial glycocalyx. Single cytoskeleton anchored rupture events represent HA molecules linked to the cytoskeleton and therefore transmitting mechanical stimuli into the inner cell compartments. Single membrane tethers would conversely represent the glycocalyx molecules connected to areas of the membrane where an abundance of signalling molecules reside.", "classifications": [ { "id": "Maki", "label": "Group Maki", "parent": "Toyoshima", "type": "group" }, { "id": "Toyoshima", "label": "Team Toyoshima", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Stefania", "last_name": "Marcotti", "name": null }, { "creator_type": "author", "first_name": "Koichiro", "last_name": "Maki", "name": null }, { "creator_type": "author", "first_name": "Gwendolen C.", "last_name": "Reilly", "name": null }, { "creator_type": "author", "first_name": "Damien", "last_name": "Lacroix", "name": null }, { "creator_type": "author", "first_name": "Taiji", "last_name": "Adachi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1371/journal.pone.0206056" }, "pmcid": { "normalized": "PMC6201909" }, "pmid": { "normalized": "30359403" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cattle", "descriptor_ui": "D002417", "major_topic": false }, { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "Cell Membrane", "descriptor_ui": "D002462", "major_topic": false }, { "descriptor": "Cytoskeleton", "descriptor_ui": "D003599", "major_topic": false }, { "descriptor": "Hyaluronic Acid", "descriptor_ui": "D006820", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Microscopy, Atomic Force", "descriptor_ui": "D018625", "major_topic": true } ], "publication": { "conference_name": null, "date": "2018", "date_precision": "year", "issue": "10", "normalized_date": "2018", "pages": "e0206056", "proceedings_title": null, "publisher": "", "title": "PloS one", "volume": "13", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "Hyaluronic acid selective anchoring to the cytoskeleton: An atomic force microscopy study.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Cysteine hydropersulphide (CysSSH) is a cysteine derivative having one additional sulphur atom bound to a cysteinyl thiol group. Recent advances in the development of analytical methods for detection and quantification of persulphides and polysulphides have revealed the biological presence, in both prokaryotes and eukaryotes, of hydropersulphides in diverse forms such as CysSSH, homocysteine hydropersulphide, glutathione hydropersulphide, bacillithiol hydropersulphide, coenzyme A hydropersulphide, and protein hydropersulphides. Owing to the chemical reactivity of the persulphide moiety, biological systems utilize persulphides as important intermediates in the synthesis of various sulphur-containing biomolecules. Accumulating evidence has revealed another important feature of persulphides: their potent reducing activity, which implies that they are implicated in the regulation of redox signalling and antioxidant functions. In this chapter, we discuss the biological occurrence and possible biosynthetic mechanisms of CysSSH and related persulphides, and we include descriptions of recent advances in the analytical methods that have been used to detect and quantitate persulphide species. We also discuss the antioxidant activity of persulphide species that contributes to protecting cells from reactive oxygen species-associated damage, and we examine the signalling roles of CysSSH in bacteria.", "classifications": [ { "id": "Akaike", "label": "Group Akaike", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Group Nishida", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Tomohiro", "last_name": "Sawa", "name": null }, { "creator_type": "author", "first_name": "Katsuhiko", "last_name": "Ono", "name": null }, { "creator_type": "author", "first_name": "Hiroyasu", "last_name": "Tsutsuki", "name": null }, { "creator_type": "author", "first_name": "Tianli", "last_name": "Zhang", "name": null }, { "creator_type": "author", "first_name": "Tomoaki", "last_name": "Ida", "name": null }, { "creator_type": "author", "first_name": "Motohiro", "last_name": "Nishida", "name": null }, { "creator_type": "author", "first_name": "Takaaki", "last_name": "Akaike", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/bs.ampbs.2018.01.002" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "29778212" } }, "mesh": [ { "descriptor": "Antioxidants", "descriptor_ui": "D000975", "major_topic": false }, { "descriptor": "Bacteria", "descriptor_ui": "D001419", "major_topic": false }, { "descriptor": "Cysteine", "descriptor_ui": "D003545", "major_topic": false }, { "descriptor": "Metabolic Networks and Pathways", "descriptor_ui": "D053858", "major_topic": true }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": true }, { "descriptor": "Stress, Physiological", "descriptor_ui": "D013312", "major_topic": false }, { "descriptor": "Sulfides", "descriptor_ui": "D013440", "major_topic": false } ], "publication": { "conference_name": null, "date": "2018", "date_precision": "year", "issue": "", "normalized_date": "2018", "pages": "1-28", "proceedings_title": null, "publisher": "", "title": "Advances in microbial physiology", "volume": "72", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "Reactive Cysteine Persulphides: Occurrence, Biosynthesis, Antioxidant Activity, Methodologies, and Bacterial Persulphide Signalling.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare disease that develops with a skin lesion and is often accompanied by leukemic transformation. The normal counterparts of BPDCN tumor cells are progenitors of plasmacytoid dendritic cells, whereas the origins are thought to be hematopoietic stem cells. Approximately 10%-20% of BPDCN patients develop other hematologic malignancies, including chronic myelomonocytic leukemia (CMML). Mutations in epigenetic regulators are frequently observed in both BPDCN and CMML tumors. Azacitidine, a drug that targets epigenetic dysregulation, is known to be an effective treatment for CMML. However, it has been used in few BPDCN patients. Here, we report a BPDCN patient with skin lesions, bone marrow infiltration, and lymphadenopathy. CMML also developed during the course of BPDCN. Azacitidine had positive effects on CMML; however, BPDCN aggressively relapsed during treatment. Two TET2 mutations were found in both BPDCN and CMML tumors; one of which was commonly identified in both tumors.", "classifications": [ { "id": "Nishikii", "label": "Group Nishikii", "parent": "Shintaku", "type": "group" }, { "id": "Shintaku", "label": "Team Shintaku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Shinichiro", "last_name": "Sukegawa", "name": null }, { "creator_type": "author", "first_name": "Mamiko", "last_name": "Sakata-Yanagimoto", "name": null }, { "creator_type": "author", "first_name": "Ryota", "last_name": "Matsuoka", "name": null }, { "creator_type": "author", "first_name": "Haruka", "last_name": "Momose", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Kiyoki", "name": null }, { "creator_type": "author", "first_name": "Masayuki", "last_name": "Noguchi", "name": null }, { "creator_type": "author", "first_name": "Naoya", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Rei", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Manabu", "last_name": "Fujimoto", "name": null }, { "creator_type": "author", "first_name": "Yasuhisa", "last_name": "Yokoyama", "name": null }, { "creator_type": "author", "first_name": "Hidekazu", "last_name": "Nishikii", "name": null }, { "creator_type": "author", "first_name": "Takayasu", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Manabu", "last_name": "Kusakabe", "name": null }, { "creator_type": "author", "first_name": "Naoki", "last_name": "Kurita", "name": null }, { "creator_type": "author", "first_name": "Naoshi", "last_name": "Obara", "name": null }, { "creator_type": "author", "first_name": "Yuichi", "last_name": "Hasegawa", "name": null }, { "creator_type": "author", "first_name": "Shigeru", "last_name": "Chiba", "name": null } ], "identifiers": { "doi": { "normalized": "10.11406/rinketsu.59.2567" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "30626790" } }, "mesh": [ { "descriptor": "Azacitidine", "descriptor_ui": "D001374", "major_topic": false }, { "descriptor": "Dendritic Cells", "descriptor_ui": "D003713", "major_topic": false }, { "descriptor": "Dioxygenases", "descriptor_ui": "D049308", "major_topic": false }, { "descriptor": "DNA-Binding Proteins", "descriptor_ui": "D004268", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Leukemia, Myelomonocytic, Chronic", "descriptor_ui": "D015477", "major_topic": false }, { "descriptor": "Proto-Oncogene Proteins", "descriptor_ui": "D011518", "major_topic": false }, { "descriptor": "Skin Neoplasms", "descriptor_ui": "D012878", "major_topic": false } ], "publication": { "conference_name": null, "date": "2018", "date_precision": "year", "issue": "12", "normalized_date": "2018", "pages": "2567-2573", "proceedings_title": null, "publisher": "", "title": "[Rinsho ketsueki] The Japanese journal of clinical hematology", "volume": "59", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "[Blastic plasmacytoid dendritic cell neoplasm accompanied by chronic myelomonocytic leukemia successfully treated with azacitidine].", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: Alzheimer's disease (AD) is a most common dementia in elderly people. Since AD symptoms resemble those of other neurodegenerative diseases, including idiopathic normal pressure hydrocephalus (iNPH), it is difficult to distinguish AD from iNPH for a precise and early diagnosis. iNPH is caused by the accumulation of cerebrospinal fluid (CSF) and involves gait disturbance, urinary incontinence, and dementia. iNPH is treatable with shunt operation which removes accumulated CSF from the brain ventricles. METHODS: We performed metabolomic analysis in the CSF of patients with AD and iNPH with capillary electrophoresis-mass spectrometry. We assessed metabolites to discriminate between AD and iNPH with Welch's t-test, receiver operating characteristic (ROC) curve analysis, and multiple logistic regression analysis. RESULTS: We found significant increased levels of glycerate and N-acetylneuraminate and significant decreased levels of serine and 2-hydroxybutyrate in the CSF of patients with AD compared to the CSF of patients with iNPH. The ROC curve analysis with these four metabolites showed that the area under the ROC curve was 0.90, indicating good discrimination between AD and iNPH. CONCLUSIONS: This study identified four metabolites that could possibly discriminate between AD and iNPH, which previous research has shown are closely related to the risk factors, pathogenesis, and symptoms of AD. Analyzing pathway-specific metabolites in the CSF of patients with AD may further elucidate the mechanism and pathogenesis of AD.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yuki", "last_name": "Nagata", "name": null }, { "creator_type": "author", "first_name": "Akiyoshi", "last_name": "Hirayama", "name": null }, { "creator_type": "author", "first_name": "Satsuki", "last_name": "Ikeda", "name": null }, { "creator_type": "author", "first_name": "Aoi", "last_name": "Shirahata", "name": null }, { "creator_type": "author", "first_name": "Futaba", "last_name": "Shoji", "name": null }, { "creator_type": "author", "first_name": "Midori", "last_name": "Maruyama", "name": null }, { "creator_type": "author", "first_name": "Mitsunori", "last_name": "Kayano", "name": null }, { "creator_type": "author", "first_name": "Masahiko", "last_name": "Bundo", "name": null }, { "creator_type": "author", "first_name": "Kotaro", "last_name": "Hattori", "name": null }, { "creator_type": "author", "first_name": "Sumiko", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Yu-Ichi", "last_name": "Goto", "name": null }, { "creator_type": "author", "first_name": "Katsuya", "last_name": "Urakami", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Kouichi", "last_name": "Ozaki", "name": null }, { "creator_type": "author", "first_name": "Shumpei", "last_name": "Niida", "name": null } ], "identifiers": { "doi": { "normalized": "10.1186/s40364-018-0119-x" }, "pmcid": { "normalized": "PMC5778653" }, "pmid": { "normalized": "29387418" } }, "mesh": [], "publication": { "conference_name": null, "date": "2018", "date_precision": "year", "issue": "", "normalized_date": "2018", "pages": "5", "proceedings_title": null, "publisher": "", "title": "Biomarker research", "volume": "6", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "Comparative analysis of cerebrospinal fluid metabolites in Alzheimer's disease and idiopathic normal pressure hydrocephalus in a Japanese cohort.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Understanding the viability of the ischemic myocardial tissue is a critical issue in determining the appropriate surgical procedure for patients with chronic heart failure after myocardial infarction (MI). Conventional MI evaluation methods are; however, preoperatively performed and/or give an indirect information of myocardial viability such as shape, color, and blood flow. In this study, we realize the evaluation of MI in patients undergoing cardiac surgery by Raman spectroscopy under label-free conditions, which is based on intrinsic molecular constituents related to myocardial viability. We identify key signatures of Raman spectra for the evaluation of myocardial viability by evaluating the infarct border zone myocardium that were excised from five patients under surgical ventricular restoration. We also obtain a prediction model to differentiate the infarcted myocardium from the non-infarcted myocardium by applying partial least squares regression-discriminant analysis (PLS-DA) to the Raman spectra. Our prediction model enables identification of the infarcted tissues and the non-infarcted tissues with sensitivities of 99.98% and 99.92%, respectively. Furthermore, the prediction model of the Raman images of the infarct border zone enabled us to visualize boundaries between these distinct regions. Our novel application of Raman spectroscopy to the human heart would be a useful means for the detection of myocardial viability during surgery.", "classifications": [ { "id": "Tanaka", "label": "Group Tanaka", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Tsunehisa", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Takeo", "last_name": "Minamikawa", "name": null }, { "creator_type": "author", "first_name": "Yoshinori", "last_name": "Harada", "name": null }, { "creator_type": "author", "first_name": "Yoshihisa", "last_name": "Yamaoka", "name": null }, { "creator_type": "author", "first_name": "Hideo", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Yaku", "name": null }, { "creator_type": "author", "first_name": "Tetsuro", "last_name": "Takamatsu", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41598-018-33025-6" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "30279495" } }, "mesh": [ { "descriptor": "Cardiac Surgical Procedures", "descriptor_ui": "D006348", "major_topic": false }, { "descriptor": "Cardiomyopathies", "descriptor_ui": "D009202", "major_topic": false }, { "descriptor": "Diagnosis, Differential", "descriptor_ui": "D003937", "major_topic": false }, { "descriptor": "Feasibility Studies", "descriptor_ui": "D005240", "major_topic": false }, { "descriptor": "Heart Ventricles", "descriptor_ui": "D006352", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Image Interpretation, Computer-Assisted", "descriptor_ui": "D007090", "major_topic": false }, { "descriptor": "Models, Cardiovascular", "descriptor_ui": "D008955", "major_topic": false }, { "descriptor": "Myocardial Infarction", "descriptor_ui": "D009203", "major_topic": false }, { "descriptor": "Myocardium", "descriptor_ui": "D009206", "major_topic": false }, { "descriptor": "Plastic Surgery Procedures", "descriptor_ui": "D019651", "major_topic": false }, { "descriptor": "Predictive Value of Tests", "descriptor_ui": "D011237", "major_topic": false }, { "descriptor": "Prognosis", "descriptor_ui": "D011379", "major_topic": false }, { "descriptor": "Sensitivity and Specificity", "descriptor_ui": "D012680", "major_topic": false }, { "descriptor": "Software", "descriptor_ui": "D012984", "major_topic": false }, { "descriptor": "Spectrum Analysis, Raman", "descriptor_ui": "D013059", "major_topic": false } ], "publication": { "conference_name": null, "date": "2018", "date_precision": "year", "issue": "", "normalized_date": "2018", "pages": "", "proceedings_title": null, "publisher": "", "title": "Scientific Reports", "volume": "8", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "Label-free Evaluation of Myocardial Infarct in Surgically Excised Ventricular Myocardium by Raman Spectroscopy.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "", "classifications": [ { "id": "Nishida", "label": "Group Nishida", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Licht", "last_name": "Miyamoto", "name": null }, { "creator_type": "author", "first_name": "Motohiro", "last_name": "Nishida", "name": null } ], "identifiers": { "doi": { "normalized": "10.1248/yakushi.18-00091-f" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "30270268" } }, "mesh": [ { "descriptor": "AMP-Activated Protein Kinases", "descriptor_ui": "D055372", "major_topic": false }, { "descriptor": "Cardiovascular Diseases", "descriptor_ui": "D002318", "major_topic": false }, { "descriptor": "Drug Discovery", "descriptor_ui": "D055808", "major_topic": false }, { "descriptor": "Drug Therapy", "descriptor_ui": "D004358", "major_topic": false }, { "descriptor": "Energy Metabolism", "descriptor_ui": "D004734", "major_topic": false }, { "descriptor": "Forecasting", "descriptor_ui": "D005544", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Life Style", "descriptor_ui": "D008019", "major_topic": true }, { "descriptor": "Sarcopenia", "descriptor_ui": "D055948", "major_topic": false } ], "publication": { "conference_name": null, "date": "2018", "date_precision": "year", "issue": "10", "normalized_date": "2018", "pages": "1255-1256", "proceedings_title": null, "publisher": "", "title": "Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan", "volume": "138", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "[Lifestyle Inspires Future Pharmacotherapy and Drug Discovery].", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Neural progenitor cells (NPCs), which are apicobasally elongated and densely packed in the developing brain, systematically move their nuclei/somata in a cell cycle-dependent manner, called interkinetic nuclear migration (IKNM): apical during G2 and basal during G1. Although intracellular molecular mechanisms of individual IKNM have been explored, how heterogeneous IKNMs are collectively coordinated is unknown. Our quantitative cell-biological and in silico analyses revealed that tissue elasticity mechanically assists an initial step of basalward IKNM. When the soma of an M-phase progenitor cell rounds up using actomyosin within the subapical space, a microzone within 10 mum from the surface, which is compressed and elastic because of the apical surface's contractility, laterally pushes the densely neighboring processes of non-M-phase cells. The pressed processes then recoil centripetally and basally to propel the nuclei/somata of the progenitor's daughter cells. Thus, indirect neighbor-assisted transfer of mechanical energy from mother to daughter helps efficient brain development.", "classifications": [ { "id": "Nagayama", "label": "Group Nagayama", "parent": "Fujiwara", "type": "group" }, { "id": "Fujiwara", "label": "Team Fujiwara", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Tomoyasu", "last_name": "Shinoda", "name": null }, { "creator_type": "author", "first_name": "Arata", "last_name": "Nagasaka", "name": null }, { "creator_type": "author", "first_name": "Yasuhiro", "last_name": "Inoue", "name": null }, { "creator_type": "author", "first_name": "Ryo", "last_name": "Higuchi", "name": null }, { "creator_type": "author", "first_name": "Yoshiaki", "last_name": "Minami", "name": null }, { "creator_type": "author", "first_name": "Kagayaki", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Takefumi", "last_name": "Kondo", "name": null }, { "creator_type": "author", "first_name": "Takumi", "last_name": "Kawaue", "name": null }, { "creator_type": "author", "first_name": "Kanako", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Naoto", "last_name": "Ueno", "name": null }, { "creator_type": "author", "first_name": "Yugo", "last_name": "Fukazawa", "name": null }, { "creator_type": "author", "first_name": "Masaharu", "last_name": "Nagayama", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Miura", "name": null }, { "creator_type": "author", "first_name": "Taiji", "last_name": "Adachi", "name": null }, { "creator_type": "author", "first_name": "Takaki", "last_name": "Miyata", "name": null } ], "identifiers": { "doi": { "normalized": "10.1371/journal.pbio.2004426" }, "pmcid": { "normalized": "PMC5931692" }, "pmid": { "normalized": "29677184" } }, "mesh": [ { "descriptor": "Actomyosin", "descriptor_ui": "D000205", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Biomechanical Phenomena", "descriptor_ui": "D001696", "major_topic": false }, { "descriptor": "Cell Cycle", "descriptor_ui": "D002453", "major_topic": false }, { "descriptor": "Cell Nucleus", "descriptor_ui": "D002467", "major_topic": false }, { "descriptor": "Cell Nucleus Division", "descriptor_ui": "D048750", "major_topic": false }, { "descriptor": "Cell Proliferation", "descriptor_ui": "D049109", "major_topic": false }, { "descriptor": "Cerebral Cortex", "descriptor_ui": "D002540", "major_topic": false }, { "descriptor": "Elasticity", "descriptor_ui": "D004548", "major_topic": false }, { "descriptor": "Embryo, Mammalian", "descriptor_ui": "D004622", "major_topic": false }, { "descriptor": "Energy Transfer", "descriptor_ui": "D004735", "major_topic": false }, { "descriptor": "Heterocyclic Compounds, 4 or More Rings", "descriptor_ui": "D006576", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred ICR", "descriptor_ui": "D008813", "major_topic": false }, { "descriptor": "Movement", "descriptor_ui": "D009068", "major_topic": false }, { "descriptor": "Neural Stem Cells", "descriptor_ui": "D058953", "major_topic": false }, { "descriptor": "Neuroepithelial Cells", "descriptor_ui": "D046569", "major_topic": false }, { "descriptor": "Time-Lapse Imaging", "descriptor_ui": "D059008", "major_topic": false } ], "publication": { "conference_name": null, "date": "2018 Apr", "date_precision": "unknown", "issue": "4", "normalized_date": null, "pages": "e2004426", "proceedings_title": null, "publisher": "", "title": "PLoS biology", "volume": "16", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "Elasticity-based boosting of neuroepithelial nucleokinesis via indirect energy transfer from mother to daughter.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "We studied angiogenesis using mathematical models describing the dynamics of tip cells. We reviewed the basic ideas of angiogenesis models and its numerical simulation technique to produce realistic computer graphics images of sprouting angiogenesis. We examined the classical model of Anderson-Chaplain using fundamental concepts of mass transport and chemical reaction with ECM degradation included. We then constructed two types of numerical schemes, model-faithful and model-driven ones, where new techniques of numerical simulation are introduced, such as transient probability, particle velocity, and Boolean variables.", "classifications": [ { "id": "Suzuki", "label": "Group Suzuki", "parent": "Takekawa", "type": "group" }, { "id": "Takekawa", "label": "Team Takekawa", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Takashi", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Dhisa", "last_name": "Minerva", "name": null }, { "creator_type": "author", "first_name": "Koichi", "last_name": "Nishiyama", "name": null }, { "creator_type": "author", "first_name": "Naohiko", "last_name": "Koshikawa", "name": null }, { "creator_type": "author", "first_name": "Mark Andrew Joseph", "last_name": "Chaplain", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/cas.13395" }, "pmcid": { "normalized": "PMC5765301" }, "pmid": { "normalized": "28892582" } }, "mesh": [ { "descriptor": "Computer Simulation", "descriptor_ui": "D003198", "major_topic": false }, { "descriptor": "Extracellular Matrix", "descriptor_ui": "D005109", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Models, Biological", "descriptor_ui": "D008954", "major_topic": false }, { "descriptor": "Models, Theoretical", "descriptor_ui": "D008962", "major_topic": false }, { "descriptor": "Neovascularization, Pathologic", "descriptor_ui": "D009389", "major_topic": false }, { "descriptor": "Tumor Microenvironment", "descriptor_ui": "D059016", "major_topic": false }, { "descriptor": "Vascular Endothelial Growth Factors", "descriptor_ui": "D042442", "major_topic": false } ], "publication": { "conference_name": null, "date": "2018 Jan", "date_precision": "unknown", "issue": "1", "normalized_date": null, "pages": "15-23", "proceedings_title": null, "publisher": "", "title": "Cancer science", "volume": "109", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "Study on the tumor-induced angiogenesis using mathematical models.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The chemical biology of thiols (RSH, e.g., cysteine and cysteine-containing proteins/peptides) has been a topic of extreme interest for many decades due to their reported roles in protein structure/folding, redox signaling, metal ligation, cellular protection, and enzymology. While many of the studies on thiol/sulfur biochemistry have focused on thiols, relatively ignored have been hydropersulfides (RSSH) and higher order polysulfur species (RSS(n) H, RSS(n) R, n > 1). Recent and provocative work has alluded to the prevalence and likely physiological importance of RSSH and related RSS(n) H. RSSH of cysteine (Cys-SSH) has been found to be prevalent in mammalian systems along with Cys-SSH-containing proteins. The RSSH functionality has not been examined to the extent of other biologically relevant sulfur derivatives (e.g., sulfenic acids, disulfides, etc.), whose roles in cell signaling are strongly indicated. The recent finding of Cys-SSH biosynthesis and translational incorporation into proteins is an unequivocal indication of its fundamental importance and necessitates a more profound look into the physiology of RSSH. In this Review, we discuss the currently reported chemical biology of RSSH (and related species) as a prelude to discussing their possible physiological roles.", "classifications": [ { "id": "Akaike", "label": "Group Akaike", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Jon M.", "last_name": "Fukuto", "name": null }, { "creator_type": "author", "first_name": "Louis J.", "last_name": "Ignarro", "name": null }, { "creator_type": "author", "first_name": "Peter", "last_name": "Nagy", "name": null }, { "creator_type": "author", "first_name": "David A.", "last_name": "Wink", "name": null }, { "creator_type": "author", "first_name": "Christopher G.", "last_name": "Kevil", "name": null }, { "creator_type": "author", "first_name": "Martin", "last_name": "Feelisch", "name": null }, { "creator_type": "author", "first_name": "Miriam M.", "last_name": "Cortese-Krott", "name": null }, { "creator_type": "author", "first_name": "Christopher L.", "last_name": "Bianco", "name": null }, { "creator_type": "author", "first_name": "Yoshito", "last_name": "Kumagai", "name": null }, { "creator_type": "author", "first_name": "Adrian J.", "last_name": "Hobbs", "name": null }, { "creator_type": "author", "first_name": "Joseph", "last_name": "Lin", "name": null }, { "creator_type": "author", "first_name": "Tomoaki", "last_name": "Ida", "name": null }, { "creator_type": "author", "first_name": "Takaaki", "last_name": "Akaike", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/1873-3468.13090" }, "pmcid": { "normalized": "PMC6033183" }, "pmid": { "normalized": "29754415" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cysteine", "descriptor_ui": "D003545", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Hydrogen Sulfide", "descriptor_ui": "D006862", "major_topic": false }, { "descriptor": "Oxidation-Reduction", "descriptor_ui": "D010084", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Sulfhydryl Compounds", "descriptor_ui": "D013438", "major_topic": false }, { "descriptor": "Sulfides", "descriptor_ui": "D013440", "major_topic": false } ], "publication": { "conference_name": null, "date": "2018 Jun", "date_precision": "unknown", "issue": "12", "normalized_date": null, "pages": "2140-2152", "proceedings_title": null, "publisher": "", "title": "FEBS letters", "volume": "592", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "Biological hydropersulfides and related polysulfides - a new concept and perspective in redox biology.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Osteoclast differentiation is a dynamic differentiation process, which is accompanied by dramatic changes in metabolic status as well as in gene expression. Recent findings have revealed an essential connection between metabolic reprogramming and dynamic gene expression changes during osteoclast differentiation. However, the upstream regulatory mechanisms that drive these metabolic changes in osteoclastogenesis remain to be elucidated. Here, we demonstrate that induced deletion of a tumor suppressor gene, Folliculin (Flcn), in mouse osteoclast precursors causes severe osteoporosis in 3 weeks through excess osteoclastogenesis. Flcn-deficient osteoclast precursors reveal cell autonomous accelerated osteoclastogenesis with increased sensitivity to receptor activator of NF-kappaB ligand (RANKL). We demonstrate that Flcn regulates oxidative phosphorylation and purine metabolism through suppression of nuclear localization of the transcription factor Tfe3, thereby inhibiting expression of its target gene Pgc1. Metabolome studies revealed that Flcn-deficient osteoclast precursors exhibit significant augmentation of oxidative phosphorylation and nucleotide production, resulting in an enhanced purinergic signaling loop that is composed of controlled ATP release and autocrine/paracrine purinergic receptor stimulation. Inhibition of this purinergic signaling loop efficiently blocks accelerated osteoclastogenesis in Flcn-deficient osteoclast precursors. Here, we demonstrate an essential and novel role of the Flcn-Tfe3-Pgc1 axis in osteoclastogenesis through the metabolic reprogramming of oxidative phosphorylation and purine metabolism. (c) 2018 The Authors Journal of Bone and Mineral Research published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research (ASBMR).", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Masaya", "last_name": "Baba", "name": null }, { "creator_type": "author", "first_name": "Mitsuhiro", "last_name": "Endoh", "name": null }, { "creator_type": "author", "first_name": "Wenjuan", "last_name": "Ma", "name": null }, { "creator_type": "author", "first_name": "Hirofumi", "last_name": "Toyama", "name": null }, { "creator_type": "author", "first_name": "Akiyoshi", "last_name": "Hirayama", "name": null }, { "creator_type": "author", "first_name": "Keizo", "last_name": "Nishikawa", "name": null }, { "creator_type": "author", "first_name": "Keiyo", "last_name": "Takubo", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Hano", "name": null }, { "creator_type": "author", "first_name": "Hisashi", "last_name": "Hasumi", "name": null }, { "creator_type": "author", "first_name": "Terumasa", "last_name": "Umemoto", "name": null }, { "creator_type": "author", "first_name": "Michihiro", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Nobuko", "last_name": "Irie", "name": null }, { "creator_type": "author", "first_name": "Chiharu", "last_name": "Esumi", "name": null }, { "creator_type": "author", "first_name": "Miho", "last_name": "Kataoka", "name": null }, { "creator_type": "author", "first_name": "Naomi", "last_name": "Nakagata", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Yao", "name": null }, { "creator_type": "author", "first_name": "Tomomi", "last_name": "Kamba", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Minami", "name": null }, { "creator_type": "author", "first_name": "Masaru", "last_name": "Ishii", "name": null }, { "creator_type": "author", "first_name": "Toshio", "last_name": "Suda", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/jbmr.3477" }, "pmcid": { "normalized": "PMC6220829" }, "pmid": { "normalized": "29893999" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Basic Helix-Loop-Helix Leucine Zipper Transcription Factors", "descriptor_ui": "D051778", "major_topic": false }, { "descriptor": "Bone Marrow", "descriptor_ui": "D001853", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Organelle Biogenesis", "descriptor_ui": "D001678", "major_topic": false }, { "descriptor": "Osteoclasts", "descriptor_ui": "D010010", "major_topic": false }, { "descriptor": "Osteogenesis", "descriptor_ui": "D010012", "major_topic": true }, { "descriptor": "Osteoporosis", "descriptor_ui": "D010024", "major_topic": false }, { "descriptor": "Oxidative Phosphorylation", "descriptor_ui": "D010085", "major_topic": false }, { "descriptor": "Proto-Oncogene Proteins", "descriptor_ui": "D011518", "major_topic": false }, { "descriptor": "Purines", "descriptor_ui": "D011687", "major_topic": false }, { "descriptor": "RAW 264.7 Cells", "descriptor_ui": "D000067996", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Transcription Factors", "descriptor_ui": "D014157", "major_topic": false }, { "descriptor": "Tumor Suppressor Proteins", "descriptor_ui": "D025521", "major_topic": false }, { "descriptor": "Up-Regulation", "descriptor_ui": "D015854", "major_topic": false } ], "publication": { "conference_name": null, "date": "2018 Oct", "date_precision": "unknown", "issue": "10", "normalized_date": null, "pages": "1785-1798", "proceedings_title": null, "publisher": "", "title": "Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research", "volume": "33", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "Folliculin Regulates Osteoclastogenesis Through Metabolic Regulation.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The reversible oxidation of protein cysteine residues (Cys-SH) is a key reaction in cellular redox signaling involving initial formation of sulfenic acids (Cys-SOH), which are commonly detected using selective dimedone-based probes. Here, we report that significant portions of dimedone-tagged proteins are susceptible to cleavage by DTT reflecting the presence of perthiosulfenic acid species (Cys-SSOH) due to similar oxidation of hydropersulfides (Cys-SSH), since Cys-S-dimedone adducts are stable toward DTT. Combined studies using molecular modeling, mass spectrometry, and cell-based experiments indicate that Cys-SSH are readily oxidized to Cys-SSOH, which forms stable adducts with dimedone-based probes. We additionally confirm the presence of Cys-SSH within protein tyrosine kinases such as EGFR, and their apparent oxidation to Cys-SSOH in response NADPH oxidase activation, suggesting that such Cys-SSH oxidation may represent a novel, as yet uncharacterized, event in redox-based signaling.", "classifications": [ { "id": "Akaike", "label": "Group Akaike", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "David E.", "last_name": "Heppner", "name": null }, { "creator_type": "author", "first_name": "Milena", "last_name": "Hristova", "name": null }, { "creator_type": "author", "first_name": "Tomoaki", "last_name": "Ida", "name": null }, { "creator_type": "author", "first_name": "Ana", "last_name": "Mijuskovic", "name": null }, { "creator_type": "author", "first_name": "Christopher M.", "last_name": "Dustin", "name": null }, { "creator_type": "author", "first_name": "Virag", "last_name": "Bogdandi", "name": null }, { "creator_type": "author", "first_name": "Jon M.", "last_name": "Fukuto", "name": null }, { "creator_type": "author", "first_name": "Tobias P.", "last_name": "Dick", "name": null }, { "creator_type": "author", "first_name": "Peter", "last_name": "Nagy", "name": null }, { "creator_type": "author", "first_name": "Jianing", "last_name": "Li", "name": null }, { "creator_type": "author", "first_name": "Takaaki", "last_name": "Akaike", "name": null }, { "creator_type": "author", "first_name": "Albert", "last_name": "van der Vliet", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.redox.2017.10.006" }, "pmcid": { "normalized": "PMC5647513" }, "pmid": { "normalized": "29054072" } }, "mesh": [ { "descriptor": "Cyclohexanones", "descriptor_ui": "D003512", "major_topic": false }, { "descriptor": "Cysteine", "descriptor_ui": "D003545", "major_topic": false }, { "descriptor": "Dithiothreitol", "descriptor_ui": "D004229", "major_topic": false }, { "descriptor": "HEK293 Cells", "descriptor_ui": "D057809", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Hydrogen Peroxide", "descriptor_ui": "D006861", "major_topic": false }, { "descriptor": "Models, Molecular", "descriptor_ui": "D008958", "major_topic": false }, { "descriptor": "NADPH Oxidases", "descriptor_ui": "D019255", "major_topic": false }, { "descriptor": "Oxidation-Reduction", "descriptor_ui": "D010084", "major_topic": false }, { "descriptor": "Protein-Tyrosine Kinases", "descriptor_ui": "D011505", "major_topic": false }, { "descriptor": "Proteins", "descriptor_ui": "D011506", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Sulfenic Acids", "descriptor_ui": "D013434", "major_topic": false }, { "descriptor": "Sulfhydryl Compounds", "descriptor_ui": "D013438", "major_topic": false } ], "publication": { "conference_name": null, "date": "2018 Apr", "date_precision": "unknown", "issue": "", "normalized_date": null, "pages": "379-385", "proceedings_title": null, "publisher": "", "title": "Redox biology", "volume": "14", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "Cysteine perthiosulfenic acid (Cys-SSOH): A novel intermediate in thiol-based redox signaling?", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Reprogramming technology has enabled the fate conversion of terminally differentiated somatic cells into pluripotent stem cells or into another differentiated state. A dynamic reorganization of epigenetic regulation takes place during cellular reprogramming. Given that reprogramming does not require changes in the underlying genome, the technology can be used to actively modify epigenetic regulation. Although reprogramming has been investigated mostly at the cellular level in vitro, studies have reported that somatic cells are reprogrammable in multicellular organisms in vivo. In vivo reprogramming provides a potential strategy for regenerative medicine. Notably, recent studies using in vivo reprogramming technology to alter epigenetic regulation at organismal levels have revealed unappreciated epigenetic mechanisms in various biological phenomena, including cancer development, tissue regeneration, aging, and rejuvenation in mammals. Moreover, in vivo reprogramming technology can be applied to abrogate epigenetic aberrations associated with aging and cancer, which raises the possibility that the technology could provide a potential strategy to control the fate of detrimental cells such as senescent cells and cancer cells in vivo. Here, we review recent progress and future perspectives of in vivo reprogramming.", "classifications": [ { "id": "Yamamoto", "label": "Group Yamamoto", "parent": "Toyoshima", "type": "group" }, { "id": "Toyoshima", "label": "Team Toyoshima", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yuko", "last_name": "Sogabe", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Seno", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Yasuhiro", "last_name": "Yamada", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/cas.13731" }, "pmcid": { "normalized": "PMC6125454" }, "pmid": { "normalized": "29989289" } }, "mesh": [ { "descriptor": "Aging", "descriptor_ui": "D000375", "major_topic": false }, { "descriptor": "Cellular Reprogramming", "descriptor_ui": "D065150", "major_topic": false }, { "descriptor": "Cellular Senescence", "descriptor_ui": "D016922", "major_topic": false }, { "descriptor": "DNA Methylation", "descriptor_ui": "D019175", "major_topic": false }, { "descriptor": "Epigenesis, Genetic", "descriptor_ui": "D044127", "major_topic": false }, { "descriptor": "Histones", "descriptor_ui": "D006657", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Induced Pluripotent Stem Cells", "descriptor_ui": "D057026", "major_topic": false }, { "descriptor": "Neoplasms", "descriptor_ui": "D009369", "major_topic": false }, { "descriptor": "Regeneration", "descriptor_ui": "D012038", "major_topic": false }, { "descriptor": "Rejuvenation", "descriptor_ui": "D012060", "major_topic": false } ], "publication": { "conference_name": null, "date": "2018 Sep", "date_precision": "unknown", "issue": "9", "normalized_date": null, "pages": "2641-2650", "proceedings_title": null, "publisher": "", "title": "Cancer science", "volume": "109", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "Unveiling epigenetic regulation in cancer, aging, and rejuvenation with in vivo reprogramming technology.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Physiological regulatory mechanisms of protein, RNA, and DNA functions include small chemical modifications, such as methylation, which are introduced or removed in a highly chemo-, regio-, and site-selective manner by methyltransferases and demethylases, respectively. However, mimicking or controlling these modifications by using labeling reagents and inhibitors remains challenging. In this Personal Account, we introduce our nascent interdisciplinary collaboration between chemists and biologists aimed at developing a basic strategy to analyse and control the methylation reactions regulated by protein methyltransferases (PMTs). We focus in particular on the structural development of chaetocin and S-adenosylmethionine to obtain PMT inhibitors and PMT substrate detectors.", "classifications": [ { "id": "Sodeoka", "label": "Group Sodeoka", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yoshihiro", "last_name": "Sohtome", "name": null }, { "creator_type": "author", "first_name": "Mikiko", "last_name": "Sodeoka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/tcr.201800118" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "30324709" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Enzyme Inhibitors", "descriptor_ui": "D004791", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Methylation", "descriptor_ui": "D008745", "major_topic": false }, { "descriptor": "Piperazines", "descriptor_ui": "D010879", "major_topic": false }, { "descriptor": "Protein Methyltransferases", "descriptor_ui": "D011496", "major_topic": false }, { "descriptor": "Proteins", "descriptor_ui": "D011506", "major_topic": false }, { "descriptor": "Proteomics", "descriptor_ui": "D040901", "major_topic": false }, { "descriptor": "S-Adenosylmethionine", "descriptor_ui": "D012436", "major_topic": false } ], "publication": { "conference_name": null, "date": "2018 Dec", "date_precision": "unknown", "issue": "12", "normalized_date": null, "pages": "1660-1671", "proceedings_title": null, "publisher": "", "title": "Chemical record (New York, N.Y.)", "volume": "18", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "Development of Chaetocin and S-Adenosylmethionine Analogues as Tools for Studying Protein Methylation.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The mechanistic details underlying the assembly of rod-shaped chromosomes during mitosis and how they segregate from each other to act as individually mobile units remain largely unknown. Here, we construct a coarse-grained physical model of chromosomal DNA and condensins, a class of large protein complexes that plays key roles in these processes. We assume that condensins have two molecular activities: consecutive loop formation in DNA and inter-condensin attractions. Our simulation demonstrates that both of these activities and their balancing acts are essential for the efficient shaping and segregation of mitotic chromosomes. Our results also demonstrate that the shaping and segregation processes are strongly correlated, implying their mechanistic coupling during mitotic chromosome assembly. Our results highlight the functional importance of inter-condensin attractions in chromosome shaping and segregation.", "classifications": [ { "id": "Mochizuki", "label": "Group Mochizuki", "parent": "Eiraku", "type": "group" }, { "id": "Eiraku", "label": "Team Eiraku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yuji", "last_name": "Sakai", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Mochizuki", "name": null }, { "creator_type": "author", "first_name": "Kazuhisa", "last_name": "Kinoshita", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Hirano", "name": null }, { "creator_type": "author", "first_name": "Masashi", "last_name": "Tachikawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1371/journal.pcbi.1006152" }, "pmcid": { "normalized": "PMC6005465" }, "pmid": { "normalized": "29912867" } }, "mesh": [ { "descriptor": "Adenosine Triphosphatases", "descriptor_ui": "D000251", "major_topic": true }, { "descriptor": "Chromosome Segregation", "descriptor_ui": "D020090", "major_topic": false }, { "descriptor": "Chromosomes", "descriptor_ui": "D002875", "major_topic": true }, { "descriptor": "Computational Biology", "descriptor_ui": "D019295", "major_topic": false }, { "descriptor": "DNA-Binding Proteins", "descriptor_ui": "D004268", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Models, Genetic", "descriptor_ui": "D008957", "major_topic": false }, { "descriptor": "Molecular Dynamics Simulation", "descriptor_ui": "D056004", "major_topic": false }, { "descriptor": "Multiprotein Complexes", "descriptor_ui": "D046912", "major_topic": true } ], "publication": { "conference_name": null, "date": "2018 Jun", "date_precision": "unknown", "issue": "6", "normalized_date": null, "pages": "e1006152", "proceedings_title": null, "publisher": "", "title": "PLoS computational biology", "volume": "14", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "Modeling the functions of condensin in chromosome shaping and segregation.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "When a cardiac muscle is held in a stretched position, its [Ca(2+)] transient increases slowly over several minutes in a process known as stress-induced slow increase in intracellular Ca(2+) concentration ([Ca(2+)](i)) (SSC). Transient receptor potential canonical (TRPC) 3 forms a non-selective cation channel regulated by the angiotensin II type 1 receptor (AT1R). In this study, we investigated the role of TRPC3 in the SSC. Isolated mouse ventricular myocytes were electrically stimulated and subjected to sustained stretch. An AT1R blocker, a phospholipase C inhibitor, and a TRPC3 inhibitor suppressed the SSC. These inhibitors also abolished the observed SSC-like slow increase in [Ca(2+)](i) induced by angiotensin II, instead of stretch. Furthermore, the SSC was not observed in TRPC3 knockout mice. Simulation and immunohistochemical studies suggest that sarcolemmal TRPC3 is responsible for the SSC. These results indicate that sarcolemmal TRPC3, regulated by AT1R, causes the SSC.", "classifications": [ { "id": "Nishida", "label": "Group Nishida", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yohei", "last_name": "Yamaguchi", "name": null }, { "creator_type": "author", "first_name": "Gentaro", "last_name": "Iribe", "name": null }, { "creator_type": "author", "first_name": "Toshiyuki", "last_name": "Kaneko", "name": null }, { "creator_type": "author", "first_name": "Ken", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Takuro", "last_name": "Numaga-Tomita", "name": null }, { "creator_type": "author", "first_name": "Motohiro", "last_name": "Nishida", "name": null }, { "creator_type": "author", "first_name": "Lutz", "last_name": "Birnbaumer", "name": null }, { "creator_type": "author", "first_name": "Keiji", "last_name": "Naruse", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/s12576-016-0519-3" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "28105583" } }, "mesh": [ { "descriptor": "Angiotensin II", "descriptor_ui": "D000804", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Calcium", "descriptor_ui": "D002118", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Myocardium", "descriptor_ui": "D009206", "major_topic": false }, { "descriptor": "Myocytes, Cardiac", "descriptor_ui": "D032383", "major_topic": false }, { "descriptor": "Receptor, Angiotensin, Type 1", "descriptor_ui": "D044140", "major_topic": false }, { "descriptor": "TRPC Cation Channels", "descriptor_ui": "D050052", "major_topic": false } ], "publication": { "conference_name": null, "date": "2018 Mar", "date_precision": "unknown", "issue": "2", "normalized_date": null, "pages": "153-164", "proceedings_title": null, "publisher": "", "title": "The journal of physiological sciences : JPS", "volume": "68", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "TRPC3 participates in angiotensin II type 1 receptor-dependent stress-induced slow increase in intracellular Ca(2+) concentration in mouse cardiomyocytes.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "A sheath-flow interface is the most common ionization technique in CE-ESI-MS. However, this interface dilutes the analytes with the sheath liquid and decreases the sensitivity. In this study, we developed a sheathless CE-MS interface to improve sensitivity. The interface was fabricated by making a small crack approximately 2 cm from the end of a capillary column fixed on a plastic plate, and then covering the crack with a dialysis membrane to prevent metabolite loss during separation. A voltage for CE separation was applied between the capillary inlet and the buffer reservoir. Under optimum conditions, 52 cationic metabolite standards were separated and selectively detected using MS. With a pressure injection of 5 kPa for 15 s (ca. 1.4 nL), the detection limits for the tested compounds were between 0.06 and 1.7 mumol/L (S/N = 3). The method was applied to analysis of cationic metabolites extracted from a small number (12 000) of cancer cells, and the number of peaks detected was about 2.5 times higher than when using conventional sheath-flow CE-MS. Because the interface is easy to construct, it is cost-effective and can be adapted to any commercially available capillaries. This method is a powerful new tool for highly sensitive CE-MS-based metabolomic analysis.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Akiyoshi", "last_name": "Hirayama", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Abe", "name": null }, { "creator_type": "author", "first_name": "Nozomi", "last_name": "Yamaguchi", "name": null }, { "creator_type": "author", "first_name": "Sho", "last_name": "Tabata", "name": null }, { "creator_type": "author", "first_name": "Masaru", "last_name": "Tomita", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/elps.201800017" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "29493797" } }, "mesh": [ { "descriptor": "Cations", "descriptor_ui": "D002412", "major_topic": false }, { "descriptor": "Electrophoresis, Capillary", "descriptor_ui": "D019075", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Metabolomics", "descriptor_ui": "D055432", "major_topic": false }, { "descriptor": "Neoplasms", "descriptor_ui": "D009369", "major_topic": false }, { "descriptor": "Spectrometry, Mass, Electrospray Ionization", "descriptor_ui": "D021241", "major_topic": false } ], "publication": { "conference_name": null, "date": "2018 Jun", "date_precision": "unknown", "issue": "11", "normalized_date": null, "pages": "1382-1389", "proceedings_title": null, "publisher": "", "title": "Electrophoresis", "volume": "39", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "Development of a sheathless CE-ESI-MS interface.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: Metabolome analysis is one of the omics which investigates the final product of a central dogma. Changes of liver metabolites during liver regeneration following hepatectomy (Hx) continue to remain unclear. The aim of the present study was to investigate the changes of liver metabolites following Hx with ischemia reperfusion (I/R) towards liver regeneration. METHODS: Twenty-three patients who underwent Hx were enrolled in this study. Non-tumor tissues were sampled immediately before and after Hx and a comparison was made between the liver samples taken before and after Hx using capillary electrophoresis (CE)-time-of-flight mass spectrometry (TOFMS) as metabolome analysis. RESULTS: The metabolic pathway showed that there was a significant increase in \"lactate\" following Hx. There was a significant decrease in metabolites only in the first half of the tricarboxylic acid cycle (TCA) cycle, and adenosine triphosphate (ATP) by anaerobiotic glycolysis did not occur in time for energy consumption of the Hx. Principal component analysis revealed remarkably different component profiles between the samples taken before and after Hx. One hundred and three metabolites were selected as critical metabolites for separating components. Valine and tryptophan increased significantly after Hx and they were regulated by resected liver volume, ischemic time and liver function. CONCLUSION: The liver metabolites changed remarkably between before and after Hx. Especially, liver valine and tryptophan were increased.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yu", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Yuji", "last_name": "Morine", "name": null }, { "creator_type": "author", "first_name": "Shuichi", "last_name": "Iwahashi", "name": null }, { "creator_type": "author", "first_name": "Tetsuya", "last_name": "Ikemoto", "name": null }, { "creator_type": "author", "first_name": "Satoru", "last_name": "Imura", "name": null }, { "creator_type": "author", "first_name": "Hisami", "last_name": "Yamanaka-Okumura", "name": null }, { "creator_type": "author", "first_name": "Akiyoshi", "last_name": "Hirayama", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Masaru", "last_name": "Tomita", "name": null }, { "creator_type": "author", "first_name": "Mitsuo", "last_name": "Shimada", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/ags3.12058" }, "pmcid": { "normalized": "PMC5980257" }, "pmid": { "normalized": "29863192" } }, "mesh": [], "publication": { "conference_name": null, "date": "2018 May", "date_precision": "unknown", "issue": "3", "normalized_date": null, "pages": "204-211", "proceedings_title": null, "publisher": "", "title": "Annals of gastroenterological surgery", "volume": "2", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "Changes of liver metabolites following hepatectomy with ischemia reperfusion towards liver regeneration.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Multiple tumor nodules are seen with increasing frequency in clinical practice. On the basis of the 2015 WHO classification of lung tumors, we assessed the reproducibility of the comprehensive histologic assessment to distinguish second primary lung cancers (SPLCs) from intrapulmonary metastases (IPMs), looking for the most distinctive histologic features. An international panel of lung pathologists reviewed a scanned sequential cohort of 126 tumors from 48 patients and recorded an agreed set of histologic features, including tumor typing and predominant pattern of adenocarcinoma, thereby opining whether the case was SPLC, IPM, or a combination thereof. Cohen κ statistics of 0.60 on overall assessment of SPLC or IPM indicated a good agreement. Likewise, there was good agreement (κ score 0.64, p < 0.0001) between WHO histologic pattern in individual cases and SPLC or IPM status, but the proportions diversified for histologic pattern and SPLC or IPM status (McNemar test, p < 0.0001). The strongest associations for distinguishing between SPLC and IPM were observed for nuclear pleomorphism, cell size, acinus formation, nucleolar size, mitotic rate, nuclear inclusions, intraalveolar clusters, and necrosis. Conversely, the associations for lymphocytosis, mucin content, lepidic growth, vascular invasion, macrophage response, clear cell change, acute inflammation keratinization, and emperipolesis did not reach significance with tumor extent. Comprehensive histologic assessment is recommended for distinguishing SPLC from IPM with good reproducibility among lung pathologists. In addition to main histologic type and predominant patterns of histologic subtypes, nuclear pleomorphism, cell size, acinus formation, nucleolar size, and mitotic rate strongly correlate with pathologic staging status.", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Andrew G.", "last_name": "Nicholson", "name": null }, { "creator_type": "author", "first_name": "Kathleen", "last_name": "Torkko", "name": null }, { "creator_type": "author", "first_name": "Patrizia", "last_name": "Viola", "name": null }, { "creator_type": "author", "first_name": "Edwina", "last_name": "Duhig", "name": null }, { "creator_type": "author", "first_name": "Kim", "last_name": "Geisinger", "name": null }, { "creator_type": "author", "first_name": "Alain C.", "last_name": "Borczuk", "name": null }, { "creator_type": "author", "first_name": "Kenzo", "last_name": "Hiroshima", "name": null }, { "creator_type": "author", "first_name": "Ming S.", "last_name": "Tsao", "name": null }, { "creator_type": "author", "first_name": "Arne", "last_name": "Warth", "name": null }, { "creator_type": "author", "first_name": "Sylvie", "last_name": "Lantuejoul", "name": null }, { "creator_type": "author", "first_name": "Prudence A.", "last_name": "Russell", "name": null }, { "creator_type": "author", "first_name": "Erik", "last_name": "Thunnissen", "name": null }, { "creator_type": "author", "first_name": "Alberto", "last_name": "Marchevsky", "name": null }, { "creator_type": "author", "first_name": "Mari", "last_name": "Mino-Kenudson", "name": null }, { "creator_type": "author", "first_name": "Mary Beth", "last_name": "Beasley", "name": null }, { "creator_type": "author", "first_name": "Johan", "last_name": "Botling", "name": null }, { "creator_type": "author", "first_name": "Sanja", "last_name": "Dacic", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null }, { "creator_type": "author", "first_name": "Masayuki", "last_name": "Noguchi", "name": null }, { "creator_type": "author", "first_name": "William D.", "last_name": "Travis", "name": null }, { "creator_type": "author", "first_name": "Keith", "last_name": "Kerr", "name": null }, { "creator_type": "author", "first_name": "Fred R.", "last_name": "Hirsch", "name": null }, { "creator_type": "author", "first_name": "Lucian R.", "last_name": "Chirieac", "name": null }, { "creator_type": "author", "first_name": "Ignacio I.", "last_name": "Wistuba", "name": null }, { "creator_type": "author", "first_name": "Andre", "last_name": "Moreira", "name": null }, { "creator_type": "author", "first_name": "Jin-Haeng", "last_name": "Chung", "name": null }, { "creator_type": "author", "first_name": "Teh Ying", "last_name": "Chou", "name": null }, { "creator_type": "author", "first_name": "Lukas", "last_name": "Bubendorf", "name": null }, { "creator_type": "author", "first_name": "Gang", "last_name": "Chen", "name": null }, { "creator_type": "author", "first_name": "Giuseppe", "last_name": "Pelosi", "name": null }, { "creator_type": "author", "first_name": "Claudia", "last_name": "Poleri", "name": null }, { "creator_type": "author", "first_name": "Frank C.", "last_name": "Detterbeck", "name": null }, { "creator_type": "author", "first_name": "Wilbur A.", "last_name": "Franklin", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.jtho.2017.10.019" }, "pmcid": { "normalized": "PMC6276791" }, "pmid": { "normalized": "29127023" } }, "mesh": [ { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Lung Neoplasms", "descriptor_ui": "D008175", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Neoplasm Metastasis", "descriptor_ui": "D009362", "major_topic": false }, { "descriptor": "Observer Variation", "descriptor_ui": "D015588", "major_topic": true }, { "descriptor": "Pathologists", "descriptor_ui": "D000072142", "major_topic": false } ], "publication": { "conference_name": null, "date": "2018 Feb", "date_precision": "unknown", "issue": "2", "normalized_date": null, "pages": "205-217", "proceedings_title": null, "publisher": "", "title": "Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer", "volume": "13", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "Interobserver Variation among Pathologists and Refinement of Criteria in Distinguishing Separate Primary Tumors from Intrapulmonary Metastases in Lung.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare subtype of myeloid neoplasm. Clonal evolution in the development of BPDCN remains to be elucidated. In the present study, we examined clonal evolution in a case of BPDCN by analyzing the distribution of gene mutations in tumor cells and non-tumor blood cells. The p.D1129fs and p.K1005fs TET2 mutations, p.P95H SRSF2 mutation, and p.L287fs NPM1 mutation were identified in a skin tumor at diagnosis and peripheral blood mononuclear cells at relapse. Notably, the p.D1129fs TET2 and p.L287fs NPM1 mutations were observed only in tumor cells, while the p.K1005fs TET2 and p.P95H SRSF2 mutations were found in both tumor cells and non-tumor blood cells. Recent genetic studies have suggested that some blood cancers may originate from clonal hematopoiesis, harboring somatic mutations. In the present case, the data suggest that BPDCN originated from clonal hematopoiesis with the p.K1005fs TET2 and p.P95H SRSF2 mutations via acquisition of the additional p.D1129fs TET2 and p.L287fs NPM1 mutations.", "classifications": [ { "id": "Nishikii", "label": "Group Nishikii", "parent": "Shintaku", "type": "group" }, { "id": "Shintaku", "label": "Team Shintaku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Sakurako", "last_name": "Suma", "name": null }, { "creator_type": "author", "first_name": "Mamiko", "last_name": "Sakata-Yanagimoto", "name": null }, { "creator_type": "author", "first_name": "Tran B.", "last_name": "Nguyen", "name": null }, { "creator_type": "author", "first_name": "Keiichiro", "last_name": "Hattori", "name": null }, { "creator_type": "author", "first_name": "Taiki", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Masayuki", "last_name": "Noguchi", "name": null }, { "creator_type": "author", "first_name": "Yasuhito", "last_name": "Nannya", "name": null }, { "creator_type": "author", "first_name": "Seishi", "last_name": "Ogawa", "name": null }, { "creator_type": "author", "first_name": "Rei", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Manabu", "last_name": "Fujimoto", "name": null }, { "creator_type": "author", "first_name": "Naoya", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Manabu", "last_name": "Kusakabe", "name": null }, { "creator_type": "author", "first_name": "Hidekazu", "last_name": "Nishikii", "name": null }, { "creator_type": "author", "first_name": "Takayasu", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Shigeru", "last_name": "Chiba", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/s12185-018-2461-z" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "29705980" } }, "mesh": [ { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Dendritic Cells", "descriptor_ui": "D003713", "major_topic": true }, { "descriptor": "Dioxygenases", "descriptor_ui": "D049308", "major_topic": false }, { "descriptor": "DNA-Binding Proteins", "descriptor_ui": "D004268", "major_topic": true }, { "descriptor": "Hematologic Neoplasms", "descriptor_ui": "D019337", "major_topic": true }, { "descriptor": "Hematopoiesis", "descriptor_ui": "D006410", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": true }, { "descriptor": "Nuclear Proteins", "descriptor_ui": "D009687", "major_topic": true }, { "descriptor": "Nucleophosmin", "descriptor_ui": "D000090243", "major_topic": false }, { "descriptor": "Proto-Oncogene Proteins", "descriptor_ui": "D011518", "major_topic": true }, { "descriptor": "Serine-Arginine Splicing Factors", "descriptor_ui": "D000068103", "major_topic": true } ], "publication": { "conference_name": null, "date": "2018 Oct", "date_precision": "unknown", "issue": "4", "normalized_date": null, "pages": "447-451", "proceedings_title": null, "publisher": "", "title": "International journal of hematology", "volume": "108", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "Blastic plasmacytoid dendritic cell neoplasm arising from clonal hematopoiesis.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "To develop a new strategy for inflamed site-specific drug delivery in the colon for the treatment of ulcerative colitis (UC), we leveraged on the interaction between myeloperoxidase (MPO) and human serum albumin (HSA) and prepared nanoparticles (HSA NPs) conjugated with 5-aminosalicylic acid (5-ASA). The 5-ASA-HSA NPs (nine molecules of 5-ASA per HSA molecule) were uniform particles with an average particle size of 190nm, a zeta potential of --11.8mV, and a polydispersity index of 0.35. This was considered a suitable particle characteristic to pass through the mucus layer and accumulate into the mucosa. The specific interaction between the 5-ASA-HSA NPs and MPO was observed using quartz crystal microbalance analysis in vitro. In addition, the 5-ASA-HSA NPs group containing one thousandth of the dose of the 5-ASA (75mug/kg) showed significantly lower disease activity index values and colon weight/length ratios in UC model mice as similar to large amount of neat 5-ASA group (75mg/kg), indicating that the therapeutic effect of the 5-ASA-HSA NP formulation was confirmed in vivo. Microscopic images of tissue sections of colon extracted from UC model mice demonstrated that HSA NPs and MPO were both localized in the colon, and this specific interaction between HSA NPs and MPO would be involved the in the therapeutic effect in vivo. Furthermore, in the 5-ASA and 5-ASA-HSA NPs groups, some inflammatory damage was observed in the colon, but the degree of damage was mild compared with the control and HSA NPs groups, suggesting mucosal repair and replacement with fibrous granulation tissue had occurred. Therefore, these data demonstrated that an HSA NP formulation has the potential to specifically deliver 5-ASA to an inflamed site where MPO is highly expressed.", "classifications": [ { "id": "Suzuki", "label": "Group Suzuki", "parent": "Takekawa", "type": "group" }, { "id": "Takekawa", "label": "Team Takekawa", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yasunori", "last_name": "Iwao", "name": null }, { "creator_type": "author", "first_name": "Izumi", "last_name": "Tomiguchi", "name": null }, { "creator_type": "author", "first_name": "Ayaka", "last_name": "Domura", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Mantaira", "name": null }, { "creator_type": "author", "first_name": "Akira", "last_name": "Minami", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Ikawa", "name": null }, { "creator_type": "author", "first_name": "Shin-Ichiro", "last_name": "Kimura", "name": null }, { "creator_type": "author", "first_name": "Shigeru", "last_name": "Itai", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.ejpb.2018.01.016" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "29407223" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Colitis", "descriptor_ui": "D003092", "major_topic": false }, { "descriptor": "Disease Models, Animal", "descriptor_ui": "D004195", "major_topic": true }, { "descriptor": "Dose-Response Relationship, Drug", "descriptor_ui": "D004305", "major_topic": false }, { "descriptor": "Drug Delivery Systems", "descriptor_ui": "D016503", "major_topic": false }, { "descriptor": "Drug Interactions", "descriptor_ui": "D004347", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred BALB C", "descriptor_ui": "D008807", "major_topic": false }, { "descriptor": "Nanoparticles", "descriptor_ui": "D053758", "major_topic": false }, { "descriptor": "Peroxidase", "descriptor_ui": "D009195", "major_topic": false }, { "descriptor": "Random Allocation", "descriptor_ui": "D011897", "major_topic": false }, { "descriptor": "Serum Albumin, Human", "descriptor_ui": "D000075462", "major_topic": false } ], "publication": { "conference_name": null, "date": "2018 Apr", "date_precision": "unknown", "issue": "", "normalized_date": null, "pages": "141-147", "proceedings_title": null, "publisher": "", "title": "European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V", "volume": "125", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "Inflamed site-specific drug delivery system based on the interaction of human serum albumin nanoparticles with myeloperoxidase in a murine model of experimental colitis.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "OBJECTIVES: The Blueprint (BP) Programmed Death Ligand 1 (PD-L1) Immunohistochemistry Comparability Project is a pivotal academic/professional society and industrial collaboration to assess the feasibility of harmonizing the clinical use of five independently developed commercial PD-L1 immunohistochemistry assays. The goal of BP phase 2 (BP2) was to validate the results obtained in BP phase 1 by using real-world clinical lung cancer samples. METHODS: BP2 were conducted using 81 lung cancer specimens of various histological and sample types, stained with all five trial-validated PD-L1 assays (22C3, 28-8, SP142, SP263, and 73-10); the slides were evaluated by an international panel of pathologists. BP2 also assessed the reliability of PD-L1 scoring by using digital images, and samples prepared for cytological examination. PD-L1 expression was assessed for percentage (tumor proportional score) of tumor cell (TC) and immune cell areas showing PD-L1 staining, with TCs scored continuously or categorically with the cutoffs used in checkpoint inhibitor trials. RESULTS: The BP2 results showed highly comparable staining by the 22C3, 28-8 and SP263 assays; less sensitivity with the SP142 assay; and higher sensitivity with the 73-10 assay to detect PD-L1 expression on TCs. Glass slide and digital image scorings were highly concordant (Pearson correlation >0.96). There was very strong reliability among pathologists in TC PD-L1 scoring with all assays (overall intraclass correlation coefficient [ICC] = 0.86-0.93), poor reliability in IC PD-L1 scoring (overall ICC = 0.18-0.19), and good agreement in assessing PD-L1 status on cytological cell block materials (ICC = 0.78-0.85). CONCLUSION: BP2 consolidates the analytical evidence for interchangeability of the 22C3, 28-8, and SP263 assays and lower sensitivity of the SP142 assay for determining tumor proportion score on TCs and demonstrates greater sensitivity of the 73-10 assay compared with that of the other assays.", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Ming Sound", "last_name": "Tsao", "name": null }, { "creator_type": "author", "first_name": "Keith M.", "last_name": "Kerr", "name": null }, { "creator_type": "author", "first_name": "Mark", "last_name": "Kockx", "name": null }, { "creator_type": "author", "first_name": "Mary-Beth", "last_name": "Beasley", "name": null }, { "creator_type": "author", "first_name": "Alain C.", "last_name": "Borczuk", "name": null }, { "creator_type": "author", "first_name": "Johan", "last_name": "Botling", "name": null }, { "creator_type": "author", "first_name": "Lukas", "last_name": "Bubendorf", "name": null }, { "creator_type": "author", "first_name": "Lucian", "last_name": "Chirieac", "name": null }, { "creator_type": "author", "first_name": "Gang", "last_name": "Chen", "name": null }, { "creator_type": "author", "first_name": "Teh-Ying", "last_name": "Chou", "name": null }, { "creator_type": "author", "first_name": "Jin-Haeng", "last_name": "Chung", "name": null }, { "creator_type": "author", "first_name": "Sanja", "last_name": "Dacic", "name": null }, { "creator_type": "author", "first_name": "Sylvie", "last_name": "Lantuejoul", "name": null }, { "creator_type": "author", "first_name": "Mari", "last_name": "Mino-Kenudson", "name": null }, { "creator_type": "author", "first_name": "Andre L.", "last_name": "Moreira", "name": null }, { "creator_type": "author", "first_name": "Andrew G.", "last_name": "Nicholson", "name": null }, { "creator_type": "author", "first_name": "Masayuki", "last_name": "Noguchi", "name": null }, { "creator_type": "author", "first_name": "Giuseppe", "last_name": "Pelosi", "name": null }, { "creator_type": "author", "first_name": "Claudia", "last_name": "Poleri", "name": null }, { "creator_type": "author", "first_name": "Prudence A.", "last_name": "Russell", "name": null }, { "creator_type": "author", "first_name": "Jennifer", "last_name": "Sauter", "name": null }, { "creator_type": "author", "first_name": "Erik", "last_name": "Thunnissen", "name": null }, { "creator_type": "author", "first_name": "Ignacio", "last_name": "Wistuba", "name": null }, { "creator_type": "author", "first_name": "Hui", "last_name": "Yu", "name": null }, { "creator_type": "author", "first_name": "Murry W.", "last_name": "Wynes", "name": null }, { "creator_type": "author", "first_name": "Melania", "last_name": "Pintilie", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null }, { "creator_type": "author", "first_name": "Fred R.", "last_name": "Hirsch", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.jtho.2018.05.013" }, "pmcid": { "normalized": "PMC8386299" }, "pmid": { "normalized": "29800747" } }, "mesh": [ { "descriptor": "B7-H1 Antigen", "descriptor_ui": "D060890", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Immunohistochemistry", "descriptor_ui": "D007150", "major_topic": false } ], "publication": { "conference_name": null, "date": "2018 Sep", "date_precision": "unknown", "issue": "9", "normalized_date": null, "pages": "1302-1311", "proceedings_title": null, "publisher": "", "title": "Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer", "volume": "13", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "PD-L1 Immunohistochemistry Comparability Study in Real-Life Clinical Samples: Results of Blueprint Phase 2 Project.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Calorie restriction (CR) being the most robust dietary intervention provides various health benefits. D-3-hydroxybutyrate (3HB), a major physiological ketone, has been proposed as an important endogenous molecule for CR. To investigate the role of 3HB in CR, we investigated potential shared mechanisms underlying increased retinal 3HB induced by CR and exogenously applied 3HB without CR to protect against ischemic retinal degeneration. The repeated elevation of retinal 3HB, with or without CR, suppressed retinal degeneration. Metabolomic analysis showed that the antioxidant pentose phosphate pathway and its limiting enzyme, glucose-6-phosphate dehydrogenase (G6PD), were concomitantly preserved. Importantly, the upregulation of nuclear factor erythroid 2 p45-related factor 2 (Nrf2), a regulator of G6PD, and elevation of the tricarboxylic acid cycle's Nrf2 activator, fumarate, were also shared. Together, our findings suggest that CR provides retinal antioxidative defense by 3HB through the antioxidant Nrf2 pathway via modification of a tricarboxylic acid cycle intermediate during 3HB metabolism.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yusuke", "last_name": "Izuta", "name": null }, { "creator_type": "author", "first_name": "Toshihiro", "last_name": "Imada", "name": null }, { "creator_type": "author", "first_name": "Ryuji", "last_name": "Hisamura", "name": null }, { "creator_type": "author", "first_name": "Erina", "last_name": "Oonishi", "name": null }, { "creator_type": "author", "first_name": "Shigeru", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Emi", "last_name": "Inagaki", "name": null }, { "creator_type": "author", "first_name": "Masataka", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Kazuo", "last_name": "Tsubota", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/acel.12699" }, "pmcid": { "normalized": "PMC5770878" }, "pmid": { "normalized": "29119686" } }, "mesh": [ { "descriptor": "3-Hydroxybutyric Acid", "descriptor_ui": "D020155", "major_topic": true }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Caloric Restriction", "descriptor_ui": "D031204", "major_topic": false }, { "descriptor": "Fumarates", "descriptor_ui": "D005650", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "NF-E2-Related Factor 2", "descriptor_ui": "D051267", "major_topic": true }, { "descriptor": "Protective Agents", "descriptor_ui": "D020011", "major_topic": true }, { "descriptor": "Rats, Wistar", "descriptor_ui": "D017208", "major_topic": false }, { "descriptor": "Retina", "descriptor_ui": "D012160", "major_topic": true } ], "publication": { "conference_name": null, "date": "2018 Feb", "date_precision": "unknown", "issue": "1", "normalized_date": null, "pages": "", "proceedings_title": null, "publisher": "", "title": "Aging cell", "volume": "17", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "Ketone body 3-hydroxybutyrate mimics calorie restriction via the Nrf2 activator, fumarate, in the retina.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "In mouse embryonic stem cells (mESCs), the expression of provirus and endogenous retroelements is epigenetically repressed. Although many cellular factors involved in retroelement silencing have been identified, the complete molecular mechanism remains elusive. In this study, we performed a genome-wide CRISPR screen to advance our understanding of retroelement silencing in mESCs. The Moloney murine leukemia virus (MLV)-based retroviral vector MSCV-GFP, which is repressed by the SETDB1/TRIM28 pathway in mESCs, was used as a reporter provirus, and we identified more than 80 genes involved in this process. In particular, ATF7IP and the BAF complex components are linked with the repression of most of the SETDB1 targets. We characterized two factors, MORC2A and RESF1, of which RESF1 is a novel molecule in retroelement silencing. Although both factors are recruited to repress provirus, their roles in repression are different. MORC2A appears to function dependent on repressive epigenetic modifications, while RESF1 regulates repressive epigenetic modifications associated with SETDB1. Our genome-wide CRISPR screen cataloged genes which function at different levels in silencing of SETDB1-target retroelements and provides a useful resource for further molecular studies.", "classifications": [ { "id": "Yusa", "label": "Group Yusa", "parent": "Eiraku", "type": "group" }, { "id": "Eiraku", "label": "Team Eiraku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Kei", "last_name": "Fukuda", "name": null }, { "creator_type": "author", "first_name": "Akihiko", "last_name": "Okuda", "name": null }, { "creator_type": "author", "first_name": "Kosuke", "last_name": "Yusa", "name": null }, { "creator_type": "author", "first_name": "Yoichi", "last_name": "Shinkai", "name": null } ], "identifiers": { "doi": { "normalized": "10.1101/gr.227280.117" }, "pmcid": { "normalized": "PMC5991520" }, "pmid": { "normalized": "29728365" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Clustered Regularly Interspaced Short Palindromic Repeats", "descriptor_ui": "D064112", "major_topic": false }, { "descriptor": "Epigenesis, Genetic", "descriptor_ui": "D044127", "major_topic": true }, { "descriptor": "Gene Silencing", "descriptor_ui": "D020868", "major_topic": false }, { "descriptor": "Histone-Lysine N-Methyltransferase", "descriptor_ui": "D011495", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Moloney murine leukemia virus", "descriptor_ui": "D008979", "major_topic": false }, { "descriptor": "Mouse Embryonic Stem Cells", "descriptor_ui": "D000066450", "major_topic": false }, { "descriptor": "Repressor Proteins", "descriptor_ui": "D012097", "major_topic": false }, { "descriptor": "Retroelements", "descriptor_ui": "D018626", "major_topic": false }, { "descriptor": "Transcription Factors", "descriptor_ui": "D014157", "major_topic": false } ], "publication": { "conference_name": null, "date": "2018 Jun", "date_precision": "unknown", "issue": "6", "normalized_date": null, "pages": "846-858", "proceedings_title": null, "publisher": "", "title": "Genome research", "volume": "28", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "A CRISPR knockout screen identifies SETDB1-target retroelement silencing factors in embryonic stem cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND/AIM: Enhancer of zeste homolog 2 (EZH2) is a histone methyltransferase that is deeply involved in cancer pathogenesis. Although clinicopathological significance of EZH2 in non-small cell lung cancer has been gradually elucidated, such significance in small cell lung cancer (SCLC) has yet to be fully investigated. PATIENTS AND METHODS: Forty patients with resected SCLC were analyzed for EZH2. EZH2 expression was evaluated using the Allred score (0-8) and was classified into negative (0-6) and positive (7 and 8). We evaluated the association between EZH2 and the clinicopathological characteristics and postoperative survivals. RESULTS: Among 40 patients, 15 (37.5%) and 25 (62.5%) were classified as being negative and positive for EZH2, respectively. Fisher's exact test demonstrated no significant associations between the positivity for EZH2 and clinicopathological characteristics. No significant differences were observed in recurrence-free and overall survivals between EZH2-negative/low and EZH2-high patients. CONCLUSION: EZH2 was frequently observed in patients with resected SCLC, but no significant associations were found between its expression and the clinicopathological characteristics and postoperative survivals.", "classifications": [ { "id": "Hamamoto", "label": "Group Hamamoto", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Gouji", "last_name": "Toyokawa", "name": null }, { "creator_type": "author", "first_name": "Kazuki", "last_name": "Takada", "name": null }, { "creator_type": "author", "first_name": "Tetsuzo", "last_name": "Tagawa", "name": null }, { "creator_type": "author", "first_name": "Fumihiko", "last_name": "Kinoshita", "name": null }, { "creator_type": "author", "first_name": "Yuka", "last_name": "Kozuma", "name": null }, { "creator_type": "author", "first_name": "Taichi", "last_name": "Matsubara", "name": null }, { "creator_type": "author", "first_name": "Naoki", "last_name": "Haratake", "name": null }, { "creator_type": "author", "first_name": "Shinkichi", "last_name": "Takamori", "name": null }, { "creator_type": "author", "first_name": "Takaki", "last_name": "Akamine", "name": null }, { "creator_type": "author", "first_name": "Fumihiko", "last_name": "Hirai", "name": null }, { "creator_type": "author", "first_name": "Yuichi", "last_name": "Yamada", "name": null }, { "creator_type": "author", "first_name": "Ryuji", "last_name": "Hamamoto", "name": null }, { "creator_type": "author", "first_name": "Yoshinao", "last_name": "Oda", "name": null }, { "creator_type": "author", "first_name": "Yoshihiko", "last_name": "Maehara", "name": null } ], "identifiers": { "doi": { "normalized": "10.21873/anticanres.12649" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "29848731" } }, "mesh": [ { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Disease-Free Survival", "descriptor_ui": "D018572", "major_topic": false }, { "descriptor": "Enhancer of Zeste Homolog 2 Protein", "descriptor_ui": "D000071221", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Immunohistochemistry", "descriptor_ui": "D007150", "major_topic": false }, { "descriptor": "Lung", "descriptor_ui": "D008168", "major_topic": false }, { "descriptor": "Lung Neoplasms", "descriptor_ui": "D008175", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Outcome Assessment, Health Care", "descriptor_ui": "D017063", "major_topic": false }, { "descriptor": "Prognosis", "descriptor_ui": "D011379", "major_topic": false }, { "descriptor": "Small Cell Lung Carcinoma", "descriptor_ui": "D055752", "major_topic": false } ], "publication": { "conference_name": null, "date": "2018 Jun", "date_precision": "unknown", "issue": "6", "normalized_date": null, "pages": "3707-3711", "proceedings_title": null, "publisher": "", "title": "Anticancer research", "volume": "38", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "Prevalence of Enhancer of Zeste Homolog 2 in Patients with Resected Small Cell Lung Cancer.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The female sex organ of the liverwort (Marchantia polymorpha) has a characteristic parasol-like form highly suitable for collecting water droplets containing sperm for fertilization. Motivated by this observation and using three-dimensional printing techniques, we develop a parasol-like rigid object that can grab, transport and release water droplets of a maximum size of about 1 cm. By combining experiments and scaling theory, we quantify the object's fundamental wetting and fluid dynamical properties. We construct a stability phase diagram and suggest that it is largely insensitive to properties of liquids such as surface tension and viscosity. A simple scaling argument is developed to explain the phase boundary. Our study provides basic design rules of a simple pipette-like device with bubble-free capture and drop of liquids, which can be used in laboratory settings and has applications within soft robotics. Through systematic experimental investigations, we suggest the optimal design criteria of the liverwort-inspired object to achieve maximal pipetting performance. We also provide, based on our scalable model experiments, a biological implication for the mechanistic advantage of this structure in liverwort reproduction.", "classifications": [ { "id": "Fujimoto", "label": "Group Fujimoto", "parent": "Ueda", "type": "group" }, { "id": "Ueda", "label": "Team Ueda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Keigo", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Tetsuya", "last_name": "Hisanaga", "name": null }, { "creator_type": "author", "first_name": "Koichi", "last_name": "Fujimoto", "name": null }, { "creator_type": "author", "first_name": "Keiji", "last_name": "Nakajima", "name": null }, { "creator_type": "author", "first_name": "Hirofumi", "last_name": "Wada", "name": null } ], "identifiers": { "doi": { "normalized": "10.1098/rsif.2017.0868" }, "pmcid": { "normalized": "PMC5908529" }, "pmid": { "normalized": "29540542" } }, "mesh": [ { "descriptor": "Biological Transport, Active", "descriptor_ui": "D001693", "major_topic": false }, { "descriptor": "Biomimetic Materials", "descriptor_ui": "D040761", "major_topic": true }, { "descriptor": "Hepatophyta", "descriptor_ui": "D035926", "major_topic": false }, { "descriptor": "Ovule", "descriptor_ui": "D056771", "major_topic": false }, { "descriptor": "Wettability", "descriptor_ui": "D017155", "major_topic": true } ], "publication": { "conference_name": null, "date": "2018 Mar", "date_precision": "unknown", "issue": "140", "normalized_date": null, "pages": "20170868", "proceedings_title": null, "publisher": "", "title": "Journal of the Royal Society, Interface", "volume": "15", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "Plant-inspired pipettes.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Impaired cell polarity is a hallmark of diseased tissue. In the cardiovascular system, laminar blood flow induces endothelial planar cell polarity, represented by elongated cell shape and asymmetric distribution of intracellular organelles along the axis of blood flow. Disrupted endothelial planar polarity is considered to be pro‐inflammatory, suggesting that the establishment of endothelial polarity elicits an anti‐inflammatory response. However, a causative relationship between polarity and inflammatory responses has not been firmly established. Here, we find that a cell polarity protein, PAR‐3, is an essential gatekeeper of GSK3β activity in response to laminar blood flow. We show that flow‐induced spatial distribution of PAR‐3/aPKCλ and aPKCλ/GSK3β complexes controls local GSK3β activity and thereby regulates endothelial planar polarity. The spatial information for GSK3β activation is essential for flow‐dependent polarity to the flow axis, but is not necessary for flow‐induced anti‐inflammatory response. Our results shed light on a novel relationship between endothelial polarity and vascular homeostasis highlighting avenues for novel therapeutic strategies.", "classifications": [], "creators": [ { "creator_type": "author", "first_name": "Takao", "last_name": "Hikita", "name": null }, { "creator_type": "author", "first_name": "Fatemeh", "last_name": "Mirzapourshafiyi", "name": null }, { "creator_type": "author", "first_name": "Pedro", "last_name": "Barbacena", "name": null }, { "creator_type": "author", "first_name": "Meghan", "last_name": "Riddell", "name": null }, { "creator_type": "author", "first_name": "Ayesha", "last_name": "Pasha", "name": null }, { "creator_type": "author", "first_name": "Mengnan", "last_name": "Li", "name": null }, { "creator_type": "author", "first_name": "Takuji", "last_name": "Kawamura", "name": null }, { "creator_type": "author", "first_name": "Ralf P.", "last_name": "Brandes", "name": null }, { "creator_type": "author", "first_name": "Tomonori", "last_name": "Hirose", "name": null }, { "creator_type": "author", "first_name": "Shigeo", "last_name": "Ohno", "name": null }, { "creator_type": "author", "first_name": "Holger", "last_name": "Gerhardt", "name": null }, { "creator_type": "author", "first_name": "Michiyuki", "last_name": "Matsuda", "name": null }, { "creator_type": "author", "first_name": "Claudio A.", "last_name": "Franco", "name": null }, { "creator_type": "author", "first_name": "Masanori", "last_name": "Nakayama", "name": null } ], "identifiers": { "doi": { "normalized": "10.15252/embr.201745253" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "30018153" } }, "mesh": [ { "descriptor": "Adaptor Proteins, Signal Transducing", "descriptor_ui": "D048868", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Aorta", "descriptor_ui": "D001011", "major_topic": false }, { "descriptor": "Atherosclerosis", "descriptor_ui": "D050197", "major_topic": false }, { "descriptor": "Cell Adhesion Molecules", "descriptor_ui": "D015815", "major_topic": false }, { "descriptor": "Cell Cycle Proteins", "descriptor_ui": "D018797", "major_topic": false }, { "descriptor": "Cell Polarity", "descriptor_ui": "D016764", "major_topic": false }, { "descriptor": "Cytoskeletal Proteins", "descriptor_ui": "D003598", "major_topic": false }, { "descriptor": "Endothelium, Vascular", "descriptor_ui": "D004730", "major_topic": false }, { "descriptor": "Gene Knockdown Techniques", "descriptor_ui": "D055785", "major_topic": false }, { "descriptor": "HEK293 Cells", "descriptor_ui": "D057809", "major_topic": false }, { "descriptor": "Homeostasis", "descriptor_ui": "D006706", "major_topic": false }, { "descriptor": "Human Umbilical Vein Endothelial Cells", "descriptor_ui": "D061307", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Inflammation", "descriptor_ui": "D007249", "major_topic": false }, { "descriptor": "Membrane Proteins", "descriptor_ui": "D008565", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Transgenic", "descriptor_ui": "D008822", "major_topic": false }, { "descriptor": "Nuclear Proteins", "descriptor_ui": "D009687", "major_topic": false }, { "descriptor": "Protein Kinase C", "descriptor_ui": "D011493", "major_topic": false }, { "descriptor": "Regional Blood Flow", "descriptor_ui": "D012039", "major_topic": false }, { "descriptor": "Repressor Proteins", "descriptor_ui": "D012097", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false } ], "publication": { "conference_name": null, "date": "2018 Sep", "date_precision": "unknown", "issue": "9", "normalized_date": null, "pages": "", "proceedings_title": null, "publisher": "", "title": "EMBO Reports", "volume": "19", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "PAR‐3 controls endothelial planar polarity and vascular inflammation under laminar flow.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "AIMS: Nitric oxide (NO) and endothelium-dependent hyperpolarization (EDH) play important roles in maintaining cardiovascular homeostasis. We have previously demonstrated that endothelial NO synthase (eNOS) plays diverse roles depending on vessel size, as a NO generating system in conduit arteries and an EDH-mediated system in resistance arteries, for which caveolin-1 (Cav-1) is involved. However, the physiological role of endothelial Cav-1 in microvessels remains to be elucidated. METHODS AND RESULTS: We newly generated endothelium-specific Cav-1-knockout (eCav-1-KO) mice. eCav-1-KO mice showed loss of endothelial Cav-1/eNOS complex and had cardiac hypertrophy despite normal blood pressure. In eCav-1-KO mice, as compared to wild-type controls, the extent of eNOS phosphorylation at inhibitory Thr495 was significantly reduced in mesenteric arteries and the heart. Isometric tension and Langendorff-perfused heart experiments showed that NO-mediated responses were enhanced, whereas EDH-mediated responses were reduced in coronary microcirculation in eCav-1-KO mice. Immunohistochemistry showed increased level of 8-nitroguanosine 3',5'-cyclic monophosphate (8-nitro-cGMP), a marker of nitrative stress, in the heart from eCav-1-KO mice. S-guanylation of cardiac H-Ras in eCav-1-KO mice was also significantly increased compared with wild-type controls. CONCLUSIONS: These results suggest that eCav-1 is involved in the protective role of EDH against nitrative stress caused by excessive NO to maintain cardiac microvascular homeostasis.", "classifications": [ { "id": "Akaike", "label": "Group Akaike", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Hiroki", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Shigeo", "last_name": "Godo", "name": null }, { "creator_type": "author", "first_name": "Saori", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Akiyo", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Yosuke", "last_name": "Ikumi", "name": null }, { "creator_type": "author", "first_name": "Shuhei", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Tomoaki", "last_name": "Ida", "name": null }, { "creator_type": "author", "first_name": "Shigemoto", "last_name": "Fujii", "name": null }, { "creator_type": "author", "first_name": "Takaaki", "last_name": "Akaike", "name": null }, { "creator_type": "author", "first_name": "Hiroaki", "last_name": "Shimokawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1097/fjc.0000000000000552" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "29419573" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Biological Factors", "descriptor_ui": "D001685", "major_topic": false }, { "descriptor": "Cardiomegaly", "descriptor_ui": "D006332", "major_topic": false }, { "descriptor": "Caveolin 1", "descriptor_ui": "D051242", "major_topic": false }, { "descriptor": "Coronary Vessels", "descriptor_ui": "D003331", "major_topic": false }, { "descriptor": "Cyclic GMP", "descriptor_ui": "D006152", "major_topic": false }, { "descriptor": "Endothelial Cells", "descriptor_ui": "D042783", "major_topic": false }, { "descriptor": "Guanosine", "descriptor_ui": "D006151", "major_topic": false }, { "descriptor": "Isolated Heart Preparation", "descriptor_ui": "D000067268", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mesenteric Arteries", "descriptor_ui": "D008638", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Microvessels", "descriptor_ui": "D055806", "major_topic": false }, { "descriptor": "Nitric Oxide", "descriptor_ui": "D009569", "major_topic": false }, { "descriptor": "Nitric Oxide Donors", "descriptor_ui": "D020030", "major_topic": false }, { "descriptor": "Nitric Oxide Synthase Type III", "descriptor_ui": "D052250", "major_topic": false }, { "descriptor": "Nitro Compounds", "descriptor_ui": "D009574", "major_topic": false }, { "descriptor": "Nitrosative Stress", "descriptor_ui": "D000073039", "major_topic": true }, { "descriptor": "Phosphorylation", "descriptor_ui": "D010766", "major_topic": false }, { "descriptor": "Protein Processing, Post-Translational", "descriptor_ui": "D011499", "major_topic": false }, { "descriptor": "Proto-Oncogene Proteins p21(ras)", "descriptor_ui": "D016283", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Vasodilator Agents", "descriptor_ui": "D014665", "major_topic": false } ], "publication": { "conference_name": null, "date": "2018 Feb", "date_precision": "unknown", "issue": "2", "normalized_date": null, "pages": "113-126", "proceedings_title": null, "publisher": "", "title": "Journal of cardiovascular pharmacology", "volume": "71", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "Important Role of Endothelial Caveolin-1 in the Protective Role of Endothelium-dependent Hyperpolarization Against Nitric Oxide-Mediated Nitrative Stress in Microcirculation in Mice.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Stabilization and variation of floral structures are indispensable for plant reproduction and evolution; however, the developmental mechanism regulating their structural robustness is largely unknown. To investigate this mechanism, we examined positional arrangement (aestivation) of excessively produced perianth organs (tepals) of six- and seven-tepaled (lobed) flowers in six Anemone species (Ranunculaceae). We found that the tepal arrangement that occurred in nature varied intraspecifically between spiral and whorled arrangements. Moreover, among the studied species, variation was commonly limited to three types, including whorls, despite five geometrically possible arrangements in six-tepaled flowers and two types among six possibilities in seven-tepaled flowers. A spiral arrangement, on the other hand, was unique to five-tepaled flowers. A spiral phyllotaxis model with stochasticity on initiating excessive primordia accounted for these limited variations in arrangement in cases when the divergence angle between preexisting primordia was less than 144 degrees . Moreover, interspecific differences in the frequency of the observed arrangements were explained by the change of model parameters that represent meristematic growth and differential organ growth. These findings suggest that the phyllotaxis parameters are responsible for not only intraspecific stability but interspecific difference of floral structure. Decreasing arrangements from six-tepaled to seven-tepaled Anemone flowers demonstrate that the stabilization occurs as development proceeds to increase the component (organ) number, in contrast from the intuition that the variation will be larger due to increasing number of possible states (arrangements).", "classifications": [ { "id": "Fujimoto", "label": "Group Fujimoto", "parent": "Ueda", "type": "group" }, { "id": "Ueda", "label": "Team Ueda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Miho S.", "last_name": "Kitazawa", "name": null }, { "creator_type": "author", "first_name": "Koichi", "last_name": "Fujimoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/s10265-018-1025-x" }, "pmcid": { "normalized": "PMC5916976" }, "pmid": { "normalized": "29589193" } }, "mesh": [ { "descriptor": "Anemone", "descriptor_ui": "D031883", "major_topic": false }, { "descriptor": "Flowers", "descriptor_ui": "D035264", "major_topic": false }, { "descriptor": "Models, Theoretical", "descriptor_ui": "D008962", "major_topic": true }, { "descriptor": "Organogenesis, Plant", "descriptor_ui": "D063246", "major_topic": true }, { "descriptor": "Reproduction", "descriptor_ui": "D012098", "major_topic": false } ], "publication": { "conference_name": null, "date": "2018 May", "date_precision": "unknown", "issue": "3", "normalized_date": null, "pages": "459-468", "proceedings_title": null, "publisher": "", "title": "Journal of plant research", "volume": "131", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "Spiral phyllotaxis underlies constrained variation in Anemone (Ranunculaceae) tepal arrangement.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Previous metabolomic analyses of cancer have revealed elevated glutathione levels in tumors. An inhibitor of cystine uptake was identified to suppress glutathione biosynthesis, leading to ferroptosis, a novel iron-dependent form of cell death that differs from apoptosis and necrosis. Glutamate-cysteine ligase (GCL) is the rate-limiting enzyme in the glutathione biosynthesis pathway. Buthionine sulfoximine (BSO), a GCL inhibitor, has previously demonstrated limited clinical benefits. Therefore, selecting patients who respond well to the inhibitor is a key approach for successful future drug development. Ferroptosis induction by BSO has not been fully examined in prior studies. Therefore, the present study investigated the pharmacological effects of BSO and the association between basal intracellular glutathione levels and sensitivity to BSO in cultured cell lines derived from various types of cancer, including those of the kidney [769P, 786-O, A-498, A704, ACHN, Caki-1, Caki-2, G401, G402, RCC4 VHL(-/-), RCC4 VHL(+/+), SK-NEP-1 and SW156] and ovaries (A2780 and A2780/CDDP). BSO was demonstrated to suppress glutathione levels and induce lipid peroxidation, thereby inhibiting cell viability. The viability-reducing effects of BSO were attenuated by ferroptosis inhibition and enhanced by iron, indicating that BSO induced ferroptosis in cancer cells. The cell lines sensitive to BSO, including G402, tended to exhibit non-significantly lower levels of glutathione compared with the BSO-insensitive cell lines, including Caki-2 (P=0.08). Patient sample data indicated the existence of a population of colorectal tumors with lower glutathione levels compared with those of matched normal tissues that might be suitable for the clinical testing of sensitivity to GCLC inhibitors. Collectively, these data suggest that GCL inhibition leads to ferroptosis in cancer cells, and that low glutathione tumor levels may be a patient selection marker for the use of GCL inhibitors in the treatment of tumors.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Satoru", "last_name": "Nishizawa", "name": null }, { "creator_type": "author", "first_name": "Hideo", "last_name": "Araki", "name": null }, { "creator_type": "author", "first_name": "Yoshinori", "last_name": "Ishikawa", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Kitazawa", "name": null }, { "creator_type": "author", "first_name": "Akito", "last_name": "Hata", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Takahito", "last_name": "Hara", "name": null } ], "identifiers": { "doi": { "normalized": "10.3892/ol.2018.8447" }, "pmcid": { "normalized": "PMC6004701" }, "pmid": { "normalized": "29928324" } }, "mesh": [], "publication": { "conference_name": null, "date": "2018 Jun", "date_precision": "unknown", "issue": "6", "normalized_date": null, "pages": "8735-8743", "proceedings_title": null, "publisher": "", "title": "Oncology letters", "volume": "15", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "Low tumor glutathione level as a sensitivity marker for glutamate-cysteine ligase inhibitors.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Interactions mediated by cell surface receptors initiate important instructive signaling cues but can be difficult to detect in biochemical assays because they are often highly transient and membrane-embedded receptors are difficult to solubilize in their native conformation. Here, we address these biochemical challenges by using a genome-scale, cell-based genetic screening approach using CRISPR gene knockout technology to identify cellular pathways required for specific cell surface recognition events. By using high-affinity monoclonal antibodies and low-affinity ligands, we determined the necessary screening parameters, including the importance of establishing binding contributions from the glycocalyx, that permitted the unequivocal identification of genes encoding directly interacting membrane-embedded receptors with high statistical confidence. Importantly, we show that this genome-wide screening approach additionally identified receptor-specific pathways that are required for functional display of receptors on the cell surface that included chaperones, enzymes that add post-translational modifications, trafficking proteins, and transcription factors. Finally, we demonstrate the utility of the approach by identifying IGF2R (insulin like growth factor 2 receptor) as a binding partner for the R2 subunit of GABA(B) receptors. We show that this interaction is direct and is critically dependent on mannose-6-phosphate, providing a mechanism for the internalization and regulation of GABA(B) receptor signaling. We conclude that this single approach can reveal both the molecular nature and the genetic pathways required for functional cell surface display of receptors recognized by antibodies, secreted proteins, and membrane-embedded ligands without the need to make any prior assumptions regarding their biochemical properties.", "classifications": [ { "id": "Yusa", "label": "Group Yusa", "parent": "Eiraku", "type": "group" }, { "id": "Eiraku", "label": "Team Eiraku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Sumana", "last_name": "Sharma", "name": null }, { "creator_type": "author", "first_name": "S. Josefin", "last_name": "Bartholdson", "name": null }, { "creator_type": "author", "first_name": "Amalie C. M.", "last_name": "Couch", "name": null }, { "creator_type": "author", "first_name": "Kosuke", "last_name": "Yusa", "name": null }, { "creator_type": "author", "first_name": "Gavin J.", "last_name": "Wright", "name": null } ], "identifiers": { "doi": { "normalized": "10.1101/gr.231183.117" }, "pmcid": { "normalized": "PMC6120632" }, "pmid": { "normalized": "29914970" } }, "mesh": [ { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Glycocalyx", "descriptor_ui": "D019276", "major_topic": false }, { "descriptor": "HEK293 Cells", "descriptor_ui": "D057809", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Membrane Proteins", "descriptor_ui": "D008565", "major_topic": false }, { "descriptor": "Protein Binding", "descriptor_ui": "D011485", "major_topic": false }, { "descriptor": "Protein Interaction Mapping", "descriptor_ui": "D025941", "major_topic": false }, { "descriptor": "Protein Processing, Post-Translational", "descriptor_ui": "D011499", "major_topic": false }, { "descriptor": "Protein Transport", "descriptor_ui": "D021381", "major_topic": false }, { "descriptor": "Proteome", "descriptor_ui": "D020543", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": true } ], "publication": { "conference_name": null, "date": "2018 Sep", "date_precision": "unknown", "issue": "9", "normalized_date": null, "pages": "1372-1382", "proceedings_title": null, "publisher": "", "title": "Genome research", "volume": "28", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "Genome-scale identification of cellular pathways required for cell surface recognition.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "", "classifications": [ { "id": "Nishikii", "label": "Group Nishikii", "parent": "Shintaku", "type": "group" }, { "id": "Shintaku", "label": "Team Shintaku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yasuhito", "last_name": "Suehara", "name": null }, { "creator_type": "author", "first_name": "Mamiko", "last_name": "Sakata-Yanagimoto", "name": null }, { "creator_type": "author", "first_name": "Keiichiro", "last_name": "Hattori", "name": null }, { "creator_type": "author", "first_name": "Toru", "last_name": "Nanmoku", "name": null }, { "creator_type": "author", "first_name": "Takayoshi", "last_name": "Itoh", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Kaji", "name": null }, { "creator_type": "author", "first_name": "Go", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Yoshiaki", "last_name": "Abe", "name": null }, { "creator_type": "author", "first_name": "Kentaro", "last_name": "Narita", "name": null }, { "creator_type": "author", "first_name": "Masami", "last_name": "Takeuchi", "name": null }, { "creator_type": "author", "first_name": "Kosei", "last_name": "Matsue", "name": null }, { "creator_type": "author", "first_name": "Taiki", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Masayuki", "last_name": "Noguchi", "name": null }, { "creator_type": "author", "first_name": "Naoko", "last_name": "Baba", "name": null }, { "creator_type": "author", "first_name": "Tatsuhiro", "last_name": "Sakamoto", "name": null }, { "creator_type": "author", "first_name": "Manabu", "last_name": "Kusakabe", "name": null }, { "creator_type": "author", "first_name": "Naoki", "last_name": "Kurita", "name": null }, { "creator_type": "author", "first_name": "Takayasu", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Yasuhisa", "last_name": "Yokoyama", "name": null }, { "creator_type": "author", "first_name": "Hidekazu", "last_name": "Nishikii", "name": null }, { "creator_type": "author", "first_name": "Naoshi", "last_name": "Obara", "name": null }, { "creator_type": "author", "first_name": "Yuichi", "last_name": "Hasegawa", "name": null }, { "creator_type": "author", "first_name": "Shigeru", "last_name": "Chiba", "name": null } ], "identifiers": { "doi": { "normalized": "10.3324/haematol.2017.178830" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "29472348" } }, "mesh": [ { "descriptor": "Biomarkers, Tumor", "descriptor_ui": "D014408", "major_topic": true }, { "descriptor": "Cell-Free Nucleic Acids", "descriptor_ui": "D000073888", "major_topic": false }, { "descriptor": "DNA, Neoplasm", "descriptor_ui": "D004273", "major_topic": false }, { "descriptor": "High-Throughput Nucleotide Sequencing", "descriptor_ui": "D059014", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Liquid Biopsy", "descriptor_ui": "D000073890", "major_topic": true }, { "descriptor": "Lymphoma, Large B-Cell, Diffuse", "descriptor_ui": "D016403", "major_topic": false }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": false }, { "descriptor": "Positron Emission Tomography Computed Tomography", "descriptor_ui": "D000072078", "major_topic": false }, { "descriptor": "Sensitivity and Specificity", "descriptor_ui": "D012680", "major_topic": false }, { "descriptor": "Sequence Analysis, DNA", "descriptor_ui": "D017422", "major_topic": false } ], "publication": { "conference_name": null, "date": "2018 Jun", "date_precision": "unknown", "issue": "6", "normalized_date": null, "pages": "e241-244", "proceedings_title": null, "publisher": "", "title": "Haematologica", "volume": "103", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "Liquid biopsy for the identification of intravascular large B-cell lymphoma.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Regulation of cortical microtubule reorganization is essential for plant cell survival under high salinity conditions. In response to salt stress, microtubules undergo rapid depolymerization followed by reassembly to form a new microtubule network that promotes cell survival; however, the upstream regulatory mechanisms for this recovery response are largely unknown. In this study, we demonstrate that ethylene signaling facilitates salt stress-induced reassembly of cortical microtubules in Arabidopsis (Arabidopsis thaliana). Microtubule depolymerization was not affected under salt stress following the suppression of ethylene signaling with Ag(+) or in ethylene-insensitive mutants, whereas microtubule reassembly was significantly inhibited. ETHYLENE-INSENSITIVE3, a key transcription factor in the ethylene signaling pathway, was shown to play a central role in microtubule reassembly under salt stress. In addition, we performed functional characterization of the microtubule-stabilizing protein WAVE-DAMPENED2-LIKE5 (WDL5), which was found to promote ethylene-associated microtubule reassembly and plant salt stress tolerance. These findings indicate that ethylene signaling regulates microtubule reassembly by up-regulating WDL5 expression in response to salt stress, thereby implicating ethylene signaling in salt-stress tolerance in plants.", "classifications": [ { "id": "Higaki", "label": "Group Higaki", "parent": "Ueda", "type": "group" }, { "id": "Ueda", "label": "Team Ueda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Liru", "last_name": "Dou", "name": null }, { "creator_type": "author", "first_name": "KaiKai", "last_name": "He", "name": null }, { "creator_type": "author", "first_name": "Takumi", "last_name": "Higaki", "name": null }, { "creator_type": "author", "first_name": "Xiangfeng", "last_name": "Wang", "name": null }, { "creator_type": "author", "first_name": "Tonglin", "last_name": "Mao", "name": null } ], "identifiers": { "doi": { "normalized": "10.1104/pp.17.01124" }, "pmcid": { "normalized": "PMC5841701" }, "pmid": { "normalized": "29431630" } }, "mesh": [ { "descriptor": "Arabidopsis", "descriptor_ui": "D017360", "major_topic": false }, { "descriptor": "Arabidopsis Proteins", "descriptor_ui": "D029681", "major_topic": false }, { "descriptor": "DNA-Binding Proteins", "descriptor_ui": "D004268", "major_topic": false }, { "descriptor": "Ethylenes", "descriptor_ui": "D005030", "major_topic": false }, { "descriptor": "Gene Knockout Techniques", "descriptor_ui": "D055786", "major_topic": false }, { "descriptor": "Microtubule-Associated Proteins", "descriptor_ui": "D008869", "major_topic": false }, { "descriptor": "Microtubules", "descriptor_ui": "D008870", "major_topic": false }, { "descriptor": "Models, Biological", "descriptor_ui": "D008954", "major_topic": false }, { "descriptor": "Nuclear Proteins", "descriptor_ui": "D009687", "major_topic": false }, { "descriptor": "Salt Stress", "descriptor_ui": "D000077323", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": true }, { "descriptor": "Transcription Factors", "descriptor_ui": "D014157", "major_topic": false } ], "publication": { "conference_name": null, "date": "2018 Mar", "date_precision": "unknown", "issue": "3", "normalized_date": null, "pages": "2071-2081", "proceedings_title": null, "publisher": "", "title": "Plant physiology", "volume": "176", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "Ethylene Signaling Modulates Cortical Microtubule Reassembly in Response to Salt Stress.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Osteoporosis is a skeletal disorder characterized by compromised bone strength and increased risk of fracture. Low bone mass and/or pre-existing bone fragility fractures serve as diagnostic criteria in deciding when to start medication for osteoporosis. Although osteoporosis is a metabolic disorder, metabolic markers to predict reduced bone mass are unknown. Here, we show serum metabolomics profiles of women grouped as pre-menopausal with normal bone mineral density (BMD) (normal estrogen and normal BMD; NN), post-menopausal with normal BMD (low estrogen and normal BMD; LN) or post-menopausal with low BMD (low estrogen and low BMD; LL) using comprehensive metabolomics analysis. To do so, we enrolled healthy volunteer and osteoporosis patient female subjects, surveyed them with a questionnaire, measured their BMD, and then undertook a comprehensive metabolomics analysis of sera of the three groups named above. We identified 24 metabolites whose levels differed significantly between NN/LN and NN/LL groups, as well as 18 or 10 metabolites whose levels differed significantly between NN/LN and LN/LL, or LN/LL and NN/LN groups, respectively. Our data shows metabolomics changes represent useful markers to predict estrogen deficiency and/or bone loss.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Takeshi", "last_name": "Miyamoto", "name": null }, { "creator_type": "author", "first_name": "Akiyoshi", "last_name": "Hirayama", "name": null }, { "creator_type": "author", "first_name": "Yuiko", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Tami", "last_name": "Koboyashi", "name": null }, { "creator_type": "author", "first_name": "Eri", "last_name": "Katsuyama", "name": null }, { "creator_type": "author", "first_name": "Hiroya", "last_name": "Kanagawa", "name": null }, { "creator_type": "author", "first_name": "Atsuhiro", "last_name": "Fujie", "name": null }, { "creator_type": "author", "first_name": "Mayu", "last_name": "Morita", "name": null }, { "creator_type": "author", "first_name": "Ryuichi", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Toshimi", "last_name": "Tando", "name": null }, { "creator_type": "author", "first_name": "Kana", "last_name": "Miyamoto", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Tsuji", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Funayama", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Masaru", "last_name": "Tomita", "name": null }, { "creator_type": "author", "first_name": "Masaya", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Morio", "last_name": "Matsumoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.bonr.2018.06.004" }, "pmcid": { "normalized": "PMC6019687" }, "pmid": { "normalized": "29955645" } }, "mesh": [], "publication": { "conference_name": null, "date": "2018 Dec", "date_precision": "unknown", "issue": "", "normalized_date": null, "pages": "11-18", "proceedings_title": null, "publisher": "", "title": "Bone reports", "volume": "9", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "Metabolomics-based profiles predictive of low bone mass in menopausal women.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "OBJECTIVE: Ketohexokinase (KHK), a primary enzyme in fructose metabolism, has two isoforms, namely, KHK-A and KHK-C. Previously, we reported that renal injury was reduced in streptozotocin-induced diabetic mice which lacked both isoforms. Although both isoforms express in kidney, it has not been elucidated whether each isoform plays distinct roles in the development of diabetic kidney disease (DKD). The aim of the study is to elucidate the role of KHK-A for DKD progression. MATERIALS AND METHODS: Diabetes was induced by five consecutive daily intraperitoneal injections of streptozotocin (50 mg/kg) in C57BL/6J wild-type mice, mice lacking KHK-A alone (KHK-A KO), and mice lacking both KHK-A and KHK-C (KHK-A/C KO). At 35 weeks, renal injury, inflammation, hypoxia, and oxidative stress were examined. Metabolomic analysis including polyol pathway, fructose metabolism, glycolysis, TCA (tricarboxylic acid) cycle, and NAD (nicotinamide adenine dinucleotide) metabolism in kidney and urine was done. RESULTS: Diabetic KHK-A KO mice developed severe renal injury compared to diabetic wild-type mice, and this was associated with further increases of intrarenal fructose, dihydroxyacetone phosphate (DHAP), TCA cycle intermediate levels, and severe inflammation. In contrast, renal injury was prevented in diabetic KHK-A/C KO mice compared to both wild-type and KHK-A KO diabetic mice. Further, diabetic KHK-A KO mice contained decreased renal NAD(+) level with the increase of renal hypoxia-inducible factor 1-alpha expression despite having increased renal nicotinamide (NAM) level. CONCLUSION: These results suggest that KHK-C might play a deleterious role in DKD progression through endogenous fructose metabolism, and that KHK-A plays a unique protective role against the development of DKD.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Tomohito", "last_name": "Doke", "name": null }, { "creator_type": "author", "first_name": "Takuji", "last_name": "Ishimoto", "name": null }, { "creator_type": "author", "first_name": "Takahiro", "last_name": "Hayasaki", "name": null }, { "creator_type": "author", "first_name": "Satsuki", "last_name": "Ikeda", "name": null }, { "creator_type": "author", "first_name": "Masako", "last_name": "Hasebe", "name": null }, { "creator_type": "author", "first_name": "Akiyoshi", "last_name": "Hirayama", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Noritoshi", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Tomoki", "last_name": "Kosugi", "name": null }, { "creator_type": "author", "first_name": "Naotake", "last_name": "Tsuboi", "name": null }, { "creator_type": "author", "first_name": "Miguel A.", "last_name": "Lanaspa", "name": null }, { "creator_type": "author", "first_name": "Richard J.", "last_name": "Johnson", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Kadomatsu", "name": null }, { "creator_type": "author", "first_name": "Shoichi", "last_name": "Maruyama", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.metabol.2018.03.020" }, "pmcid": { "normalized": "PMC6394855" }, "pmid": { "normalized": "29604362" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Diabetes Mellitus, Experimental", "descriptor_ui": "D003921", "major_topic": false }, { "descriptor": "Diabetic Nephropathies", "descriptor_ui": "D003928", "major_topic": false }, { "descriptor": "Fructokinases", "descriptor_ui": "D005631", "major_topic": false }, { "descriptor": "Kidney", "descriptor_ui": "D007668", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Oxidative Stress", "descriptor_ui": "D018384", "major_topic": false } ], "publication": { "conference_name": null, "date": "2018 Aug", "date_precision": "unknown", "issue": "", "normalized_date": null, "pages": "161-170", "proceedings_title": null, "publisher": "", "title": "Metabolism: clinical and experimental", "volume": "85", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "Lacking ketohexokinase-A exacerbates renal injury in streptozotocin-induced diabetic mice.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Infrared thermal imaging of brain temperature changes is useful for evaluating cortical activity and disease states, such as stroke. However, the changes depend on a balance between changes in heat generation from metabolism and in heat convection related to blood flow. To discriminate between these effects and gain a clearer understanding of neurovascular metabolic coupling, brain temperature imaging must be improved to measure temperature and blood flow simultaneously. We develop an imaging technique that shows a two-dimensional (2-D) distribution of absolute brain temperature and relative cerebral blood flow changes in anesthetized rats by combining infrared thermal imaging with laser speckle imaging. The changes in brain metabolism and cerebral blood flow are achieved using two different anesthetics (isoflurane and α-chloralose) to evaluate our system. Isoflurane increased cerebral blood flow but decreased metabolism, whereas α-chloralose decreased both parameters. This technique enables simultaneous visualization of brain surface changes in temperature and cerebral blood flow in the same regions. This imaging system will permit further study of neurovascular metabolic coupling in normal and diseased brains.", "classifications": [ { "id": "Suzuki", "label": "Group Suzuki", "parent": "Takekawa", "type": "group" }, { "id": "Takekawa", "label": "Team Takekawa", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Takashi", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Naoya", "last_name": "Oishi", "name": null }, { "creator_type": "author", "first_name": "Hidenao", "last_name": "Fukuyama", "name": null } ], "identifiers": { "doi": { "normalized": "10.1117/1.jbo.24.3.031014" }, "pmcid": { "normalized": "PMC6975233" }, "pmid": { "normalized": "30468045" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Body Temperature", "descriptor_ui": "D001831", "major_topic": false }, { "descriptor": "Brain", "descriptor_ui": "D001921", "major_topic": false }, { "descriptor": "Brain Mapping", "descriptor_ui": "D001931", "major_topic": false }, { "descriptor": "Cerebrovascular Circulation", "descriptor_ui": "D002560", "major_topic": false }, { "descriptor": "Infrared Rays", "descriptor_ui": "D007259", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Thermography", "descriptor_ui": "D013817", "major_topic": false } ], "publication": { "conference_name": null, "date": "2018 Nov", "date_precision": "unknown", "issue": "3", "normalized_date": null, "pages": "1-11", "proceedings_title": null, "publisher": "", "title": "Journal of biomedical optics", "volume": "24", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "Simultaneous infrared thermal imaging and laser speckle imaging of brain temperature and cerebral blood flow in rats.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Recent sequencing studies demonstrated the MYD88 L265P mutation in more than 70% of primary central nervous system lymphomas (PCNSL), and the clinical significance of this mutation has been proposed as diagnostic and prognostic markers in PCNSL. In contrast, mutational analyses using cell‐free DNAs have been reported in a variety of systemic lymphomas. To investigate how sensitively the MYD88 L265P mutation can be identified in cell‐free DNA from PCNSL patients, we carried out droplet digital PCR (ddPCR) and targeted deep sequencing (TDS) in 14 consecutive PCNSL patients from whom paired tumor‐derived DNA and cell‐free DNA was available at diagnosis. The MYD88 L265P mutation was found in tumor‐derived DNA from all 14 patients (14/14, 100%). In contrast, among 14 cell‐free DNAs evaluated by ddPCR (14/14) and TDS (13/14), the MYD88 L265P mutation was detected in eight out of 14 (ddPCR) and in 0 out of 13 (TDS) samples, implying dependence on the detection method. After chemotherapy, the MYD88 L265P mutation in cell‐free DNAs was traced in five patients; unexpectedly, the mutations disappeared after chemotherapy was given, and they remained undetectable in all patients. These observations suggest that ddPCR can sensitively detect the MYD88 L265P mutation in cell‐free DNA and could be used as non‐invasive diagnostics, but may not be applicable for monitoring minimal residual diseases in PCNSL.", "classifications": [ { "id": "Nishikii", "label": "Group Nishikii", "parent": "Shintaku", "type": "group" }, { "id": "Shintaku", "label": "Team Shintaku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Keiichiro", "last_name": "Hattori", "name": null }, { "creator_type": "author", "first_name": "Mamiko", "last_name": "Sakata‐Yanagimoto", "name": null }, { "creator_type": "author", "first_name": "Yasuhito", "last_name": "Suehara", "name": null }, { "creator_type": "author", "first_name": "Yasuhisa", "last_name": "Yokoyama", "name": null }, { "creator_type": "author", "first_name": "Takayasu", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Naoki", "last_name": "Kurita", "name": null }, { "creator_type": "author", "first_name": "Hidekazu", "last_name": "Nishikii", "name": null }, { "creator_type": "author", "first_name": "Naoshi", "last_name": "Obara", "name": null }, { "creator_type": "author", "first_name": "Shingo", "last_name": "Takano", "name": null }, { "creator_type": "author", "first_name": "Eiichi", "last_name": "Ishikawa", "name": null }, { "creator_type": "author", "first_name": "Akira", "last_name": "Matsumura", "name": null }, { "creator_type": "author", "first_name": "Yuichi", "last_name": "Hasegawa", "name": null }, { "creator_type": "author", "first_name": "Shigeru", "last_name": "Chiba", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/cas.13450" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "29151258" } }, "mesh": [ { "descriptor": "Central Nervous System Neoplasms", "descriptor_ui": "D016543", "major_topic": false }, { "descriptor": "DNA", "descriptor_ui": "D004247", "major_topic": false }, { "descriptor": "Drug Therapy", "descriptor_ui": "D004358", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "High-Throughput Nucleotide Sequencing", "descriptor_ui": "D059014", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": true }, { "descriptor": "Myeloid Differentiation Factor 88", "descriptor_ui": "D053594", "major_topic": false }, { "descriptor": "Polymerase Chain Reaction", "descriptor_ui": "D016133", "major_topic": false }, { "descriptor": "Retrospective Studies", "descriptor_ui": "D012189", "major_topic": false }, { "descriptor": "Sequence Analysis, DNA", "descriptor_ui": "D017422", "major_topic": false }, { "descriptor": "Treatment Outcome", "descriptor_ui": "D016896", "major_topic": false } ], "publication": { "conference_name": null, "date": "2018 Jan", "date_precision": "unknown", "issue": "1", "normalized_date": null, "pages": "225-230", "proceedings_title": null, "publisher": "", "title": "Cancer Science", "volume": "109", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "Clinical significance of disease‐specific MYD88 mutations in circulating DNA in primary central nervous system lymphoma.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The aim of the present study was to investigate the prognostic value of the C-reactive protein-to-albumin ratio (CAR) and compare it with other inflammation-based prognostic scores (Glasgow prognostic score, modified Glasgow prognostic score, neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, prognostic nutritional index and prognostic index) in patients with esophageal squamous cell cancer (ESCC). A database of 116 patients with primary ESCC who underwent treatment at the Division of Surgical Oncology at Nagasaki University Hospital between January 2007 and August 2014 was retrospectively reviewed and the correlations between CAR and overall survival (OS) were investigated. Kaplan-Meier and Cox regression analyses were used to assess independent prognostic factors. The area under the curve (AUC) was used to compare the prognostic value of different scores. According to the receiver operator characteristics analysis, the recommended cut-off value for CAR was 0.042, with an AUC of 0.678 (sensitivity 31.1%, specificity 66.7%). Thus, patients were dichotomized into low (<0.042) and high (>/=0.042) CAR groups. On multivariate analysis, CAR was found to be significantly associated with OS in patients with ESCC [hazard ratio (HR)=2.350; 95% confidence interval (CI): 1.189-4.650; P=0.014], as was tumor-node-metastasis stage (HR=3.059; 95% CI: 1.422-6.582; P=0.004). In addition, CAR had a higher AUC value (0.678) compared with several other systemic inflammation-based prognostic scores (P<0.001). This study suggested that CAR is a novel and promising inflammation-based prognostic score in patients with ESCC. Due to its simplicity, affordability and availability, CAR may be important for improving clinical decision-making and may contribute to more rational study design and analyses.", "classifications": [ { "id": "Hamamoto", "label": "Group Hamamoto", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Masaki", "last_name": "Kunizaki", "name": null }, { "creator_type": "author", "first_name": "Tetsuro", "last_name": "Tominaga", "name": null }, { "creator_type": "author", "first_name": "Kouki", "last_name": "Wakata", "name": null }, { "creator_type": "author", "first_name": "Takuro", "last_name": "Miyazaki", "name": null }, { "creator_type": "author", "first_name": "Keitaro", "last_name": "Matsumoto", "name": null }, { "creator_type": "author", "first_name": "Yorihisa", "last_name": "Sumida", "name": null }, { "creator_type": "author", "first_name": "Shigekazu", "last_name": "Hidaka", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Yamasaki", "name": null }, { "creator_type": "author", "first_name": "Toru", "last_name": "Yasutake", "name": null }, { "creator_type": "author", "first_name": "Terumitu", "last_name": "Sawai", "name": null }, { "creator_type": "author", "first_name": "Ryuji", "last_name": "Hamamoto", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Nanashima", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Nagayasu", "name": null } ], "identifiers": { "doi": { "normalized": "10.3892/mco.2017.1527" }, "pmcid": { "normalized": "PMC5776425" }, "pmid": { "normalized": "29435305" } }, "mesh": [], "publication": { "conference_name": null, "date": "2018 Feb", "date_precision": "unknown", "issue": "2", "normalized_date": null, "pages": "370-374", "proceedings_title": null, "publisher": "", "title": "Molecular and clinical oncology", "volume": "8", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "Clinical significance of the C-reactive protein-to-albumin ratio for the prognosis of patients with esophageal squamous cell carcinoma.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Root hairs elongate by tip growth and simultaneously harden the shank by constructing the inner secondary cell wall layer. While much is known about the process of tip growth(1), almost nothing is known about the mechanism by which root hairs harden the shank. Here we show that phosphatidylinositol-3,5-bisphosphate (PtdIns(3,5)P(2)), the enzymatic product of FORMATION OF APLOID AND BINUCLEATE CELLS 1 (FAB1), is involved in the hardening of the shank in root hairs in Arabidopsis. FAB1 and PtdIns(3,5)P(2) localize to the plasma membrane along the shank of growing root hairs. By contrast, phosphatidylinositol 4-phosphate 5-kinase 3 (PIP5K3) and PtdIns(4,5)P(2) localize to the apex of the root hair where they are required for tip growth. Reduction of FAB1 function results in the formation of wavy root hairs while those of the wild type are straight. The localization of FAB1 in the plasma membrane of the root hair shank requires the activity of Rho-related GTPases from plants 10 (ROP10) and localization of ROP10 requires FAB1 activity. Computational modelling of root hair morphogenesis successfully reproduces the wavy root hair phenotype. Taken together, these data demonstrate that root hair shank hardening requires PtdIns(3,5)P(2)/ROP10 signalling.", "classifications": [ { "id": "Higaki", "label": "Group Higaki", "parent": "Ueda", "type": "group" }, { "id": "Ueda", "label": "Team Ueda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Tomoko", "last_name": "Hirano", "name": null }, { "creator_type": "author", "first_name": "Hiroki", "last_name": "Konno", "name": null }, { "creator_type": "author", "first_name": "Seiji", "last_name": "Takeda", "name": null }, { "creator_type": "author", "first_name": "Liam", "last_name": "Dolan", "name": null }, { "creator_type": "author", "first_name": "Mariko", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Aoyama", "name": null }, { "creator_type": "author", "first_name": "Takumi", "last_name": "Higaki", "name": null }, { "creator_type": "author", "first_name": "Hisako", "last_name": "Takigawa-Imamura", "name": null }, { "creator_type": "author", "first_name": "Masa H.", "last_name": "Sato", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41477-018-0277-8" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "30390081" } }, "mesh": [ { "descriptor": "Arabidopsis", "descriptor_ui": "D017360", "major_topic": false }, { "descriptor": "Arabidopsis Proteins", "descriptor_ui": "D029681", "major_topic": false }, { "descriptor": "Gene Expression Regulation, Plant", "descriptor_ui": "D018506", "major_topic": false }, { "descriptor": "Phosphatidylinositol 3-Kinases", "descriptor_ui": "D019869", "major_topic": false }, { "descriptor": "Phosphatidylinositol Phosphates", "descriptor_ui": "D018129", "major_topic": false }, { "descriptor": "Phosphotransferases (Alcohol Group Acceptor)", "descriptor_ui": "D017853", "major_topic": false }, { "descriptor": "Plant Roots", "descriptor_ui": "D018517", "major_topic": false } ], "publication": { "conference_name": null, "date": "2018 Nov", "date_precision": "unknown", "issue": "11", "normalized_date": null, "pages": "888-897", "proceedings_title": null, "publisher": "", "title": "Nature plants", "volume": "4", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "PtdIns(3,5)P(2) mediates root hair shank hardening in Arabidopsis.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Root growth is controlled by mechanisms underlying cell division and cell elongation, which respond to various internal and external factors. In Arabidopsis (Arabidopsis thaliana), cells produced in the proximal meristem (PM) elongate and differentiate in the transition zone (TZ) and the elongation/differentiation zone (EDZ). Previous studies have demonstrated that endoreplication is involved in root cell elongation; however, the manner by which cells increase in length by more than 2-fold remains unknown. Here, we show that epidermal and cortical cells in Arabidopsis roots undergo two modes of rapid cell elongation: the first rapid cell elongation occurs at the border of the proximal meristem and the TZ, and the second mode occurs during the transition from the TZ to the EDZ. Our previous study showed that cytokinin signaling promotes endoreplication, which triggers the first rapid cell elongation. Our cytological and genetic data revealed that the second rapid cell elongation involves dynamic actin reorganization independent of endoreplication. Cytokinins promote actin bundling and the resultant second rapid cell elongation through activating the signaling pathway involving the cytokinin receptors ARABIDOPSIS HISTIDINE KINASE3 (AHK3) and AHK4 and the B-type transcription factor ARABIDOPSIS RESPONSE REGULATOR2. Our results suggest that cytokinins promote the two modes of rapid cell elongation by controlling distinct cellular events: endoreplication and actin reorganization.", "classifications": [ { "id": "Higaki", "label": "Group Higaki", "parent": "Ueda", "type": "group" }, { "id": "Ueda", "label": "Team Ueda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Hirotomo", "last_name": "Takatsuka", "name": null }, { "creator_type": "author", "first_name": "Takumi", "last_name": "Higaki", "name": null }, { "creator_type": "author", "first_name": "Masaaki", "last_name": "Umeda", "name": null } ], "identifiers": { "doi": { "normalized": "10.1104/pp.18.00557" }, "pmcid": { "normalized": "PMC6236612" }, "pmid": { "normalized": "30185441" } }, "mesh": [ { "descriptor": "Actins", "descriptor_ui": "D000199", "major_topic": false }, { "descriptor": "Arabidopsis", "descriptor_ui": "D017360", "major_topic": false }, { "descriptor": "Arabidopsis Proteins", "descriptor_ui": "D029681", "major_topic": false }, { "descriptor": "Cell Division", "descriptor_ui": "D002455", "major_topic": false }, { "descriptor": "Cell Enlargement", "descriptor_ui": "D049108", "major_topic": false }, { "descriptor": "Cytokinins", "descriptor_ui": "D003583", "major_topic": false }, { "descriptor": "Endoreduplication", "descriptor_ui": "D062951", "major_topic": false }, { "descriptor": "Gene Expression Regulation, Plant", "descriptor_ui": "D018506", "major_topic": false }, { "descriptor": "Histidine Kinase", "descriptor_ui": "D000071677", "major_topic": false }, { "descriptor": "Models, Biological", "descriptor_ui": "D008954", "major_topic": false }, { "descriptor": "Plant Growth Regulators", "descriptor_ui": "D010937", "major_topic": false }, { "descriptor": "Protein Kinases", "descriptor_ui": "D011494", "major_topic": false }, { "descriptor": "Receptors, Cell Surface", "descriptor_ui": "D011956", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Transcription Factors", "descriptor_ui": "D014157", "major_topic": false } ], "publication": { "conference_name": null, "date": "2018 Nov", "date_precision": "unknown", "issue": "3", "normalized_date": null, "pages": "1130-1141", "proceedings_title": null, "publisher": "", "title": "Plant physiology", "volume": "178", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "Actin Reorganization Triggers Rapid Cell Elongation in Roots.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Insulin resistance is a condition in which there is a defect in insulin actions to induce glucose uptake into the cells. Overstimulation of beta2-adrenergic receptors (beta2ARs) is associated with the pathogenesis of insulin resistance in the heart. However, the mechanisms by which beta2-agonists affect insulin resistance in the heart are incompletely understood. The beta2-agonists are used for treatment of asthma due to bronchodilating effects. We also investigated the effects of beta2-agonists in human bronchial smooth muscle (HBSM) cells. In this study, we demonstrate that chronic treatment with salbutamol, salmeterol, and formoterol inhibited insulin-induced glucose uptake and GLUT4 synthesis in H9c2 myoblast cells. Sustained beta2AR stimulation also attenuated GLUT4 translocation to the plasma membrane, whereas short-term stimulation had no effect. In HBSM cells, prolonged treatment with beta2-agonists had no effect on insulin-induced glucose uptake and did not alter insulin-induced expressions of GLUT1, GLUT4, and GLUT10. In addition, genetic polymorphisms at amino acid positions 16 and 27 of beta2AR are linked to insulin resistance by significant suppression of GLUT4 translocation compared to wild-type. Thus, prolonged beta2AR stimulation by beta2-agonists impairs insulin actions through suppression of GLUT synthesis and translocation only in H9c2 cells.", "classifications": [ { "id": "Nishida", "label": "Group Nishida", "parent": "Nishida", "type": "group" }, { "id": "Nishimura", "label": "Group Nishimura", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Warisara", "last_name": "Parichatikanond", "name": null }, { "creator_type": "author", "first_name": "Akiyuki", "last_name": "Nishimura", "name": null }, { "creator_type": "author", "first_name": "Motohiro", "last_name": "Nishida", "name": null }, { "creator_type": "author", "first_name": "Supachoke", "last_name": "Mangmool", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.jphs.2018.09.007" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "30322801" } }, "mesh": [ { "descriptor": "Adrenergic beta-2 Receptor Agonists", "descriptor_ui": "D058666", "major_topic": false }, { "descriptor": "Albuterol", "descriptor_ui": "D000420", "major_topic": false }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Formoterol Fumarate", "descriptor_ui": "D000068759", "major_topic": false }, { "descriptor": "Glucose", "descriptor_ui": "D005947", "major_topic": false }, { "descriptor": "Glucose Transport Proteins, Facilitative", "descriptor_ui": "D051246", "major_topic": false }, { "descriptor": "Glucose Transporter Type 1", "descriptor_ui": "D051272", "major_topic": false }, { "descriptor": "Glucose Transporter Type 4", "descriptor_ui": "D051275", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Insulin", "descriptor_ui": "D007328", "major_topic": false }, { "descriptor": "Insulin Antagonists", "descriptor_ui": "D007329", "major_topic": false }, { "descriptor": "Insulin Resistance", "descriptor_ui": "D007333", "major_topic": false }, { "descriptor": "Polymorphism, Genetic", "descriptor_ui": "D011110", "major_topic": false }, { "descriptor": "Receptors, Adrenergic, beta-2", "descriptor_ui": "D018343", "major_topic": false }, { "descriptor": "Salmeterol Xinafoate", "descriptor_ui": "D000068299", "major_topic": false } ], "publication": { "conference_name": null, "date": "2018 Nov", "date_precision": "unknown", "issue": "3", "normalized_date": null, "pages": "184-191", "proceedings_title": null, "publisher": "", "title": "Journal of pharmacological sciences", "volume": "138", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "Prolonged stimulation of beta2-adrenergic receptor with beta2-agonists impairs insulin actions in H9c2 cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: Endoscopic findings have now become nearly as detailed as histopathological findings. Thus, one-to-one correspondence and precise feedback of histopathological findings is very desirable but may be very difficult to accomplish. We describe a systematic process called the Kyoto One-to-One Correspondence Method (the KOTO Method) that allows detailed adjustments of endoscopic findings to match histopathological findings. METHODS AND RESULTS: By comparing endoscopic and stereoscopic images of the gastric mucosa, we could obtain one-to-one correspondence between endoscopic images and equivalent histology in 44 of 47 fields. CONCLUSIONS: The histological structure of gastric cancers of the same histological subtype may not be similar. One-to-one correspondence between endoscopic images and gastric mucosal histology (histopathology-oriented correspondence) will improve endoscopic diagnosis and provide more useful information for pathological diagnosis.", "classifications": [ { "id": "Tanaka", "label": "Group Tanaka", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yasuko", "last_name": "Fujita", "name": null }, { "creator_type": "author", "first_name": "Mitsuo", "last_name": "Kishimoto", "name": null }, { "creator_type": "author", "first_name": "Osamu", "last_name": "Dohi", "name": null }, { "creator_type": "author", "first_name": "Kazuhiro", "last_name": "Kamada", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Majima", "name": null }, { "creator_type": "author", "first_name": "Reiko", "last_name": "Kimura-Tsuchiya", "name": null }, { "creator_type": "author", "first_name": "Nobuaki", "last_name": "Yagi", "name": null }, { "creator_type": "author", "first_name": "Hideyuki", "last_name": "Konishi", "name": null }, { "creator_type": "author", "first_name": "Yuji", "last_name": "Naito", "name": null }, { "creator_type": "author", "first_name": "Yoshinori", "last_name": "Harada", "name": null }, { "creator_type": "author", "first_name": "Hideo", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Eiichi", "last_name": "Konishi", "name": null }, { "creator_type": "author", "first_name": "Tamotsu", "last_name": "Sugai", "name": null }, { "creator_type": "author", "first_name": "Akio", "last_name": "Yanagisawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/s10120-017-0762-1" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "28875341" } }, "mesh": [ { "descriptor": "Cytodiagnosis", "descriptor_ui": "D003581", "major_topic": false }, { "descriptor": "Endoscopy", "descriptor_ui": "D004724", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Image Interpretation, Computer-Assisted", "descriptor_ui": "D007090", "major_topic": false }, { "descriptor": "Retrospective Studies", "descriptor_ui": "D012189", "major_topic": false }, { "descriptor": "Stomach Neoplasms", "descriptor_ui": "D013274", "major_topic": false } ], "publication": { "conference_name": null, "date": "2018 May", "date_precision": "unknown", "issue": "3", "normalized_date": null, "pages": "573-577", "proceedings_title": null, "publisher": "", "title": "Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association", "volume": "21", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "How to adjust endoscopic findings to histopathological findings of the stomach: a \"histopathology-oriented\" correspondence method helps to understand endoscopic findings.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Hirondellea species are common inhabitants in the hadal region deeper than 7,000 m. We found that Hirondellea gigas thrived in the Challenger Deep possessed polysaccharide hydrolases as digestive enzymes. To obtain various enzymes of other H. gigas, we captured amphipods from the Japan Trench, and Izu-Ogasawara (Bonin) Trench. A phylogenetic analysis based on the cytochrome oxidase I gene showed close relationships among amphipods, despite the geographic distance between the localities. However, several differences in enzymatic properties were observed in these H. gigas specimens. We also carried out RNA sequencing of H. gigas from the Izu-Ogasawara Trench. The cellulase gene of H. gigas was highly homologous to cellobiohydrolase of Glucosyl Hydrolase family 7 (GH7). On the other hand, enzymatic properties of H. gigas's cellulase were different from those of typical GH7 cellobiohydrolase. Thus, these results indicate that hadal-zone amphipod can be good candidates as the new enzyme resource.", "classifications": [ { "id": "Nikaido", "label": "Group Nikaido", "parent": "Fujiwara", "type": "group" }, { "id": "Fujiwara", "label": "Team Fujiwara", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Hideki", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Takahiko", "last_name": "Nagahama", "name": null }, { "creator_type": "author", "first_name": "Wataru", "last_name": "Arai", "name": null }, { "creator_type": "author", "first_name": "Yohei", "last_name": "Sasagawa", "name": null }, { "creator_type": "author", "first_name": "Mana", "last_name": "Umeda", "name": null }, { "creator_type": "author", "first_name": "Tetsutaro", "last_name": "Hayashi", "name": null }, { "creator_type": "author", "first_name": "Itoshi", "last_name": "Nikaido", "name": null }, { "creator_type": "author", "first_name": "Hiromi", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Kazumasa", "last_name": "Oguri", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Kitazato", "name": null }, { "creator_type": "author", "first_name": "Kantaro", "last_name": "Fujioka", "name": null }, { "creator_type": "author", "first_name": "Yukari", "last_name": "Kido", "name": null }, { "creator_type": "author", "first_name": "Hideto", "last_name": "Takami", "name": null } ], "identifiers": { "doi": { "normalized": "10.1080/09168451.2018.1459178" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "29623763" } }, "mesh": [ { "descriptor": "Amphipoda", "descriptor_ui": "D033304", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Aquatic Organisms", "descriptor_ui": "D059001", "major_topic": false }, { "descriptor": "Cellulase", "descriptor_ui": "D002480", "major_topic": false }, { "descriptor": "Cellulose 1,4-beta-Cellobiosidase", "descriptor_ui": "D043366", "major_topic": false }, { "descriptor": "Hydrolases", "descriptor_ui": "D006867", "major_topic": false }, { "descriptor": "Kinetics", "descriptor_ui": "D007700", "major_topic": false }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": false }, { "descriptor": "Phylogeny", "descriptor_ui": "D010802", "major_topic": false }, { "descriptor": "Polysaccharides", "descriptor_ui": "D011134", "major_topic": false }, { "descriptor": "Seawater", "descriptor_ui": "D012623", "major_topic": false }, { "descriptor": "Sequence Analysis, RNA", "descriptor_ui": "D017423", "major_topic": false }, { "descriptor": "Substrate Specificity", "descriptor_ui": "D013379", "major_topic": false } ], "publication": { "conference_name": null, "date": "2018 Jul", "date_precision": "unknown", "issue": "7", "normalized_date": null, "pages": "1123-1133", "proceedings_title": null, "publisher": "", "title": "Bioscience, biotechnology, and biochemistry", "volume": "82", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "Polysaccharide hydrolase of the hadal zone amphipods Hirondellea gigas.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Over the past decade, multiple stem cell compartments have been identified within the epidermis. These stem cell pools have different transcriptional properties, proliferative modes and anatomical locations, and they maintain distinct epidermal compartments. The importance of this stem cell heterogeneity and compartmentalization has been understood as a key feature in epidermal homeostasis. However, recent studies have revealed that these heterogeneous stem cells themselves act as a niche for neighboring cells, thereby establishing spatially and temporally patterned epidermal-dermal functional units. These studies provide a new perspective for interpreting the biological significance of stem cell heterogeneity and compartmentalization beyond their role in epidermal maintenance.", "classifications": [ { "id": "Fujiwara", "label": "Group Fujiwara", "parent": "Fujiwara", "type": "group" }, { "id": "Fujiwara", "label": "Team Fujiwara", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Hironobu", "last_name": "Fujiwara", "name": null }, { "creator_type": "author", "first_name": "Ko", "last_name": "Tsutsui", "name": null }, { "creator_type": "author", "first_name": "Ritsuko", "last_name": "Morita", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/dgd.12577" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "30449051" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Communication", "descriptor_ui": "D002450", "major_topic": false }, { "descriptor": "Epidermal Cells", "descriptor_ui": "D000078404", "major_topic": false }, { "descriptor": "Epidermis", "descriptor_ui": "D004817", "major_topic": false }, { "descriptor": "Homeostasis", "descriptor_ui": "D006706", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Models, Biological", "descriptor_ui": "D008954", "major_topic": false }, { "descriptor": "Stem Cell Niche", "descriptor_ui": "D055153", "major_topic": false }, { "descriptor": "Stem Cells", "descriptor_ui": "D013234", "major_topic": false } ], "publication": { "conference_name": null, "date": "2018 Dec", "date_precision": "unknown", "issue": "9", "normalized_date": null, "pages": "531-541", "proceedings_title": null, "publisher": "", "title": "Development, growth & differentiation", "volume": "60", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "Multi-tasking epidermal stem cells: Beyond epidermal maintenance.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "In living cells, chemical reactions form complex networks. Dynamics arising from such networks are the origins of biological functions. We propose a mathematical method to analyze bifurcation behaviors of network systems using their structures alone. Specifically, a whole network is decomposed into subnetworks, and for each of them the bifurcation condition can be studied independently. Further, parameters inducing bifurcations and chemicals exhibiting bifurcations can be determined on the network. We illustrate our theory using hypothetical and real networks.", "classifications": [ { "id": "Mochizuki", "label": "Group Mochizuki", "parent": "Eiraku", "type": "group" }, { "id": "Eiraku", "label": "Team Eiraku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Takashi", "last_name": "Okada", "name": null }, { "creator_type": "author", "first_name": "Je-Chiang", "last_name": "Tsai", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Mochizuki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1103/physreve.98.012417" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "30110840" } }, "mesh": [], "publication": { "conference_name": null, "date": "2018 Jul", "date_precision": "unknown", "issue": "1-1", "normalized_date": null, "pages": "012417", "proceedings_title": null, "publisher": "", "title": "Physical review. E", "volume": "98", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "Structural bifurcation analysis in chemical reaction networks.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The Japanese Society of Medical Oncology (JSMO) previously published 2 editions of the clinical guidelines: \"Japanese guidelines for testing of KRAS gene mutation in colorectal cancer\" in 2008 and \"Japanese Society of Medical Oncology Clinical Guidelines: RAS (KRAS/NRAS) mutation testing in colorectal cancer patients\" in 2014. These guidelines have contributed to the proper use of KRAS and RAS mutation testing, respectively. Recently, clinical utility, particularly for colorectal cancer (CRC) patients with BRAF V600E mutation or DNA mismatch-repair (MMR) deficiency, has been established. Therefore, the guideline members decided these genetic alterations should also be involved. The aim of this revision is to properly carry out testing for BRAF V600E mutation and MMR deficiency in addition to RAS mutation. The revised guidelines include the basic requirements for testing for these genetic alterations based on recent scientific evidence. Furthermore, because clinical utility of comprehensive genetic testing using next-generation sequencing and somatic gene testing of analyzing circulating tumor DNA has increasingly evolved with recent advancements in testing technology, we noted the current situation and prospects for these testing technologies and their clinical implementation in the revised guidelines.", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Kentaro", "last_name": "Yamazaki", "name": null }, { "creator_type": "author", "first_name": "Hiroya", "last_name": "Taniguchi", "name": null }, { "creator_type": "author", "first_name": "Takayuki", "last_name": "Yoshino", "name": null }, { "creator_type": "author", "first_name": "Kiwamu", "last_name": "Akagi", "name": null }, { "creator_type": "author", "first_name": "Hideyuki", "last_name": "Ishida", "name": null }, { "creator_type": "author", "first_name": "Hiromichi", "last_name": "Ebi", "name": null }, { "creator_type": "author", "first_name": "Kaname", "last_name": "Nakatani", "name": null }, { "creator_type": "author", "first_name": "Kei", "last_name": "Muro", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null }, { "creator_type": "author", "first_name": "Kensei", "last_name": "Yamaguchi", "name": null }, { "creator_type": "author", "first_name": "Katsuya", "last_name": "Tsuchihara", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/cas.13617" }, "pmcid": { "normalized": "PMC5989850" }, "pmid": { "normalized": "29873882" } }, "mesh": [ { "descriptor": "Colorectal Neoplasms", "descriptor_ui": "D015179", "major_topic": false }, { "descriptor": "DNA Mismatch Repair", "descriptor_ui": "D053843", "major_topic": false }, { "descriptor": "Genetic Testing", "descriptor_ui": "D005820", "major_topic": false }, { "descriptor": "GTP Phosphohydrolases", "descriptor_ui": "D020558", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Japan", "descriptor_ui": "D007564", "major_topic": false }, { "descriptor": "Medical Oncology", "descriptor_ui": "D008495", "major_topic": false }, { "descriptor": "Membrane Proteins", "descriptor_ui": "D008565", "major_topic": false }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": false }, { "descriptor": "Practice Guidelines as Topic", "descriptor_ui": "D017410", "major_topic": true }, { "descriptor": "Proto-Oncogene Proteins B-raf", "descriptor_ui": "D048493", "major_topic": false }, { "descriptor": "Proto-Oncogene Proteins p21(ras)", "descriptor_ui": "D016283", "major_topic": false }, { "descriptor": "Societies, Medical", "descriptor_ui": "D012955", "major_topic": false } ], "publication": { "conference_name": null, "date": "2018 Jun", "date_precision": "unknown", "issue": "6", "normalized_date": null, "pages": "2074-2079", "proceedings_title": null, "publisher": "", "title": "Cancer science", "volume": "109", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "Japanese Society of Medical Oncology Clinical Guidelines: Molecular Testing for Colorectal Cancer Treatment, Third Edition.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Lung cancer is the leading cause of cancer death worldwide. Most of lung cancers develop sporadically and thus inherited lung cancers are rare. Several reports show that germline mutations in the kinase domain of epidermal growth factor receptor (EGFR) such as R776G, R776H, T790M, V843I and P848L, predispose to develop lung cancer. Most lung cancer cases with germline EGFR T790M mutations had secondary EGFR somatic mutations. Never smokers with germline EGFR T790M mutations develop lung cancer more frequently than ever smokers. In addition, germline EGFR T790M mutations favored female gender. Therefore, germline EGFR T790M mutations result in a unique inherited lung cancer syndrome targeting never smokers. The authors previously reported a Japanese familial lung cancer pedigree with germline mutations in the transmembrane domain of human epidermal growth factor receptor 2 (HER2). The female proband and her mother in this pedigree, who were light or never smokers, developed multiple lung adenocarcinomas, and had germline HER2 G660D mutations. They had no EGFR somatic mutations or other genes known to cause lung cancers. Although we know only one pedigree with germline HER2 mutations, these mutations may also cause inherited lung cancers targeting female never smokers. Based on our in vitro analyses, we administered HER2 inhibitor afatinib to the proband and achieved partial response. These lung cancers arising from germline mutations of receptor tyrosine kinases such as EGFR and HER2 may have different features from those with sporadic mutations.", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Hiromasa", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null }, { "creator_type": "author", "first_name": "Shinichi", "last_name": "Toyooka", "name": null } ], "identifiers": { "doi": { "normalized": "10.21037/tlcr.2018.06.01" }, "pmcid": { "normalized": "PMC6131180" }, "pmid": { "normalized": "30225213" } }, "mesh": [], "publication": { "conference_name": null, "date": "2018 Aug", "date_precision": "unknown", "issue": "4", "normalized_date": null, "pages": "498-504", "proceedings_title": null, "publisher": "", "title": "Translational lung cancer research", "volume": "7", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "Inherited lung cancer syndromes targeting never smokers.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Understanding the basis of regeneration of each tissue and organ, and incorporating this knowledge into clinical treatments for degenerative tissues and organs in patients, are major goals for researchers in regenerative biology. Here we provide an overview of current work, from high-regeneration animal models, to stem cell-based culture models, transplantation technologies, large-animal chimeric models, and programmable nuclease-based genome-editing technologies. Three-dimensional culture generating organoids, which represents intact tissue/organ identity including cell fate and morphology are getting more general approaches in the fields by taking advantage of embryonic stem cells, induced pluripotent stem cells and adult stem cells. The organoid culture system potentially has profound impact on the field of regenerative medicine. We also emphasize that the large animal model, in particular pig model would be a hope to manufacture humanized organs in in vivo empty (vacant) niche, which now potentially allows not only appropriate cell fate identity but nearly the same property as human organs in size. Therefore, integrative and collaborative researches across different fields might be critical to the aims needed in clinical trial.", "classifications": [ { "id": "Eiraku", "label": "Group Eiraku", "parent": "Eiraku", "type": "group" }, { "id": "Eiraku", "label": "Team Eiraku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Nozomu", "last_name": "Takata", "name": null }, { "creator_type": "author", "first_name": "Mototsugu", "last_name": "Eiraku", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s10038-017-0348-0" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "29192237" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Gene Editing", "descriptor_ui": "D000072669", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Regeneration", "descriptor_ui": "D012038", "major_topic": true }, { "descriptor": "Regenerative Medicine", "descriptor_ui": "D044968", "major_topic": false }, { "descriptor": "Stem Cells", "descriptor_ui": "D013234", "major_topic": true } ], "publication": { "conference_name": null, "date": "2018 Feb", "date_precision": "unknown", "issue": "2", "normalized_date": null, "pages": "165-178", "proceedings_title": null, "publisher": "", "title": "Journal of human genetics", "volume": "63", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "Stem cells and genome editing: approaches to tissue regeneration and regenerative medicine.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "It is widely accepted that aberrant activation of the Wnt signaling pathway is responsible for the development of precursor lesions of colorectal cancer (CRC). However, the molecular mechanisms involved in the process of progression from these precursor lesions to invasive lesions of CRC are not fully understood. Recently, we reported that constitutive activation of MAPK accompanied by downregulation of dual-specificity phosphatase 4 (DUSP4), a MAPK phosphatase, contributes to the progression of precursor lesions in the pancreas. In this study, we found that downregulation of DUSP4 was related to constitutive activation of ERKs in CRC cells. Restoration of DUSP4 resulted in inactivation of ERKs, leading to suppression of both proliferation and invasiveness, as shown by treatment with an MEK inhibitor. Furthermore, immunohistochemistry revealed that DUSP4 expression was upregulated in the superficial region of CRC tissue, whereas it was significantly downregulated in the deep region. In contrast, ERKs in the deep region were markedly hyperactivated compared to those in the superficial region. These results suggest that activation of the MAPK signaling pathway caused by downregulation of DUSP4 is responsible for progression of CRCs and would be a promising therapeutic target.", "classifications": [ { "id": "Takekawa", "label": "Group Takekawa", "parent": "Takekawa", "type": "group" }, { "id": "Takekawa", "label": "Team Takekawa", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Michihiro", "last_name": "Ichimanda", "name": null }, { "creator_type": "author", "first_name": "Naoki", "last_name": "Hijiya", "name": null }, { "creator_type": "author", "first_name": "Yoshiyuki", "last_name": "Tsukamoto", "name": null }, { "creator_type": "author", "first_name": "Tomohisa", "last_name": "Uchida", "name": null }, { "creator_type": "author", "first_name": "Chisato", "last_name": "Nakada", "name": null }, { "creator_type": "author", "first_name": "Tomonori", "last_name": "Akagi", "name": null }, { "creator_type": "author", "first_name": "Tsuyoshi", "last_name": "Etoh", "name": null }, { "creator_type": "author", "first_name": "Hidekatsu", "last_name": "Iha", "name": null }, { "creator_type": "author", "first_name": "Masafumi", "last_name": "Inomata", "name": null }, { "creator_type": "author", "first_name": "Mutsuhiro", "last_name": "Takekawa", "name": null }, { "creator_type": "author", "first_name": "Masatsugu", "last_name": "Moriyama", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/cas.13444" }, "pmcid": { "normalized": "PMC5765293" }, "pmid": { "normalized": "29150975" } }, "mesh": [ { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Cell Proliferation", "descriptor_ui": "D049109", "major_topic": false }, { "descriptor": "Colorectal Neoplasms", "descriptor_ui": "D015179", "major_topic": false }, { "descriptor": "Down-Regulation", "descriptor_ui": "D015536", "major_topic": true }, { "descriptor": "Dual-Specificity Phosphatases", "descriptor_ui": "D054637", "major_topic": false }, { "descriptor": "Extracellular Signal-Regulated MAP Kinases", "descriptor_ui": "D048049", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Gene Expression Regulation, Neoplastic", "descriptor_ui": "D015972", "major_topic": false }, { "descriptor": "HCT116 Cells", "descriptor_ui": "D045325", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Mitogen-Activated Protein Kinase Phosphatases", "descriptor_ui": "D054639", "major_topic": false }, { "descriptor": "Neoplasm Invasiveness", "descriptor_ui": "D009361", "major_topic": false }, { "descriptor": "Phosphorylation", "descriptor_ui": "D010766", "major_topic": false } ], "publication": { "conference_name": null, "date": "2018 Jan", "date_precision": "unknown", "issue": "1", "normalized_date": null, "pages": "250-258", "proceedings_title": null, "publisher": "", "title": "Cancer science", "volume": "109", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "Downregulation of dual-specificity phosphatase 4 enhances cell proliferation and invasiveness in colorectal carcinomas.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Lung metastasis is a major cause of mortality in patients with osteosarcoma (OS). A better understanding of the molecular mechanism of OS lung metastasis may facilitate development of new therapeutic strategies to prevent the metastasis. We have established high‐ and low‐metastatic sublines (LM8‐H and LM8‐L, respectively) from Dunn OS cell line LM8 by using in vivo image‐guided screening. Among the genes whose expression was significantly increased in LM8‐H compared to LM8‐L, the transcription factor lymphoid enhancer‐binding factor 1 (LEF1) was identified as a factor that promotes LM8‐H cell extravasation into the lungs. To identify downstream effectors of LEF1 that are involved in OS lung metastasis, 13 genes were selected based on LM8 microarray data and genomewide meta‐analysis of a public database for OS patients. Among them, the cytoglobin (Cygb) gene was identified as a key effector in promoting OS extravasation into the lungs. CYGB overexpression increased the extravasation ability of LM8‐L cells, whereas knocking out the Cygb gene in LM8‐H cells reduced this ability. Our results showed a novel LEF1‐CYGB axis in OS lung metastasis and may provide a new way of developing therapeutic strategies to prevent OS lung metastasis.", "classifications": [ { "id": "Kuchimaru", "label": "Group Kuchimaru", "parent": "Shintaku", "type": "group" }, { "id": "Shintaku", "label": "Team Shintaku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Mongkol", "last_name": "Pongsuchart", "name": null }, { "creator_type": "author", "first_name": "Takahiro", "last_name": "Kuchimaru", "name": null }, { "creator_type": "author", "first_name": "Sakiko", "last_name": "Yonezawa", "name": null }, { "creator_type": "author", "first_name": "Diem Thi Phuong", "last_name": "Tran", "name": null }, { "creator_type": "author", "first_name": "Nguyen The", "last_name": "Kha", "name": null }, { "creator_type": "author", "first_name": "Ngoc Thi Hong", "last_name": "Hoang", "name": null }, { "creator_type": "author", "first_name": "Tetsuya", "last_name": "Kadonosono", "name": null }, { "creator_type": "author", "first_name": "Shinae", "last_name": "Kizaka‐Kondoh", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/cas.13702" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "29927026" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Bone Neoplasms", "descriptor_ui": "D001859", "major_topic": false }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Cytoglobin", "descriptor_ui": "D000078842", "major_topic": false }, { "descriptor": "Globins", "descriptor_ui": "D005914", "major_topic": false }, { "descriptor": "Lung Neoplasms", "descriptor_ui": "D008175", "major_topic": false }, { "descriptor": "Lymphoid Enhancer-Binding Factor 1", "descriptor_ui": "D051821", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred BALB C", "descriptor_ui": "D008807", "major_topic": false }, { "descriptor": "Mice, Inbred C3H", "descriptor_ui": "D008809", "major_topic": false }, { "descriptor": "Osteosarcoma", "descriptor_ui": "D012516", "major_topic": false } ], "publication": { "conference_name": null, "date": "2018 Sep", "date_precision": "unknown", "issue": "9", "normalized_date": null, "pages": "2746-2756", "proceedings_title": null, "publisher": "", "title": "Cancer Science", "volume": "109", "year": 2018 }, "ssbd": { "database": [], "repository": [] }, "title": "Novel lymphoid enhancer‐binding factor 1‐cytoglobin axis promotes extravasation of osteosarcoma cells into the lungs.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Hepatocellular carcinoma (HCC) is a major type of liver cancer caused by the hepatitis B and C viruses, alcohol and exposure to aflatoxin. For HCC treatment, anticancer drugs have been widely used, but drug resistance in advanced HCC is an important problem, resulting in a continuous need for novel therapeutic targets. Therefore, in this study, we established a screening pipeline based on RNA-seq to screen novel therapeutic/prognostic targets in HCC and identified PRMT1 (Protein Arginine Methyltransferase 1). In the prognostic analysis, the overexpression of PRMT1 was clearly associated with poor prognosis in a number of HCC patient cohorts. Moreover, after PRMT1 knockdown, HCC cell lines exhibited cell growth and spheroid formation suppression, an increase in Sub-G1 cells by FACS analysis, and enrichment of the cell cycle pathway via functional enrichment analysis. With these results, we demonstrated that PRMT1 could be a novel prognostic marker and therapeutic target for HCC therapy.", "classifications": [ { "id": "Hamamoto", "label": "Group Hamamoto", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Jea-Woon", "last_name": "Ryu", "name": null }, { "creator_type": "author", "first_name": "Seon-Kyu", "last_name": "Kim", "name": null }, { "creator_type": "author", "first_name": "Mi-Young", "last_name": "Son", "name": null }, { "creator_type": "author", "first_name": "Su-Jin", "last_name": "Jeon", "name": null }, { "creator_type": "author", "first_name": "Jung-Hwa", "last_name": "Oh", "name": null }, { "creator_type": "author", "first_name": "Jung Hwa", "last_name": "Lim", "name": null }, { "creator_type": "author", "first_name": "Sunwha", "last_name": "Cho", "name": null }, { "creator_type": "author", "first_name": "Cho-Rok", "last_name": "Jung", "name": null }, { "creator_type": "author", "first_name": "Ryuji", "last_name": "Hamamoto", "name": null }, { "creator_type": "author", "first_name": "Dae-Soo", "last_name": "Kim", "name": null }, { "creator_type": "author", "first_name": "Hyun-Soo", "last_name": "Cho", "name": null } ], "identifiers": { "doi": { "normalized": "10.18632/oncotarget.23296" }, "pmcid": { "normalized": "PMC5777784" }, "pmid": { "normalized": "29383172" } }, "mesh": [], "publication": { "conference_name": null, "date": "2017 Dec 29", "date_precision": "day", "issue": "70", "normalized_date": "2017-12-29", "pages": "115444-115455", "proceedings_title": null, "publisher": "", "title": "Oncotarget", "volume": "8", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Novel prognostic marker PRMT1 regulates cell growth via downregulation of CDKN1A in HCC.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Organismal lifespan is highly plastic in response to environmental cues, and dietary restriction (DR) is the most robust way to extend lifespan in various species. Recent studies have shown that sex also is an important factor for lifespan regulation; however, it remains largely unclear how these two factors, food and sex, interact in lifespan regulation. The nematode Caenorhabditis elegans has two sexes, hermaphrodite and male, and only the hermaphrodites are essential for the short-term succession of the species. Here, we report an extreme sexual dimorphism in the responsiveness to DR in C. elegans; the essential hermaphrodites show marked longevity responses to various forms of DR, but the males show few longevity responses and sustain reproductive ability. Our analysis reveals that the sex determination pathway and the steroid hormone receptor DAF-12 regulate the sex-specific DR responsiveness, integrating sex and environmental cues to determine organismal lifespan.", "classifications": [ { "id": "Yamamoto", "label": "Group Yamamoto", "parent": "Toyoshima", "type": "group" }, { "id": "Toyoshima", "label": "Team Toyoshima", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Sakiko", "last_name": "Honjoh", "name": null }, { "creator_type": "author", "first_name": "Akiko", "last_name": "Ihara", "name": null }, { "creator_type": "author", "first_name": "Yukiko", "last_name": "Kajiwara", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Eisuke", "last_name": "Nishida", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.celrep.2017.11.108" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "29281814" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Caenorhabditis elegans", "descriptor_ui": "D017173", "major_topic": false }, { "descriptor": "Caenorhabditis elegans Proteins", "descriptor_ui": "D029742", "major_topic": false }, { "descriptor": "Caloric Restriction", "descriptor_ui": "D031204", "major_topic": true }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Hermaphroditic Organisms", "descriptor_ui": "D057850", "major_topic": false }, { "descriptor": "Longevity", "descriptor_ui": "D008136", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Models, Genetic", "descriptor_ui": "D008957", "major_topic": false }, { "descriptor": "Sex Characteristics", "descriptor_ui": "D012727", "major_topic": true }, { "descriptor": "Transcription, Genetic", "descriptor_ui": "D014158", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Dec 26", "date_precision": "day", "issue": "13", "normalized_date": "2017-12-26", "pages": "3646-3652", "proceedings_title": null, "publisher": "", "title": "Cell reports", "volume": "21", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "The Sexual Dimorphism of Dietary Restriction Responsiveness in Caenorhabditis elegans.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Silver nanoparticles (AgNPs) and their assembled nanostructures such as core/satellite nanoassemblies are quite attractive in plasmonic-based applications. However, one biggest drawback of the AgNPs is the poor chemical stability which also greatly limits their applications. We report fine Au coating on synthesized quasi-spherical silver nanoparticles (AgNSs) with few atomic layers to several nanometers by stoichiometric method. The fine Au coating layer was confirmed by energy-dispersive X-ray spectroscopy elemental mapping and aberration-corrected high-angle annular dark-field scanning transmission electron microscopy. The optimized minimal thickness of Au coating layer on different sized AgNSs (22 nm Ag@0.9 nm Au, 44 nm Ag@1.8 nm Au, 75 nm Ag@2.9 nm Au, and 103 nm Ag@0.9 nm Au) was determined by extreme chemical stability tests using H(2)O(2), NaSH, and H(2)S gas. The thin Au coating layer on AgNSs did not affect their plasmonic-based applications. The core/satellite assemblies based on Ag@Au NPs showed the comparable SERS intensity and uniformity three times higher than that of noncoated Ag core/satellites. The Ag@Au core/satellites also showed high stability in intracellular SERS imaging for at least two days, while the SERS of the noncoated Ag core/satellites decayed significantly. These spherical Ag@Au NPs can be widely used and have great advantages in plasmon-based applications, intracellular SERS probes, and other biological and analytical studies.", "classifications": [ { "id": "Fujita", "label": "Group Fujita", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Zhiqiang", "last_name": "Zhang", "name": null }, { "creator_type": "author", "first_name": "Kazuki", "last_name": "Bando", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Taguchi", "name": null }, { "creator_type": "author", "first_name": "Kentaro", "last_name": "Mochizuki", "name": null }, { "creator_type": "author", "first_name": "Kazuhisa", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Hidehiro", "last_name": "Yasuda", "name": null }, { "creator_type": "author", "first_name": "Katsumasa", "last_name": "Fujita", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Kawata", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/acsami.7b14976" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "29171749" } }, "mesh": [], "publication": { "conference_name": null, "date": "2017 Dec 20", "date_precision": "day", "issue": "50", "normalized_date": "2017-12-20", "pages": "44027-44037", "proceedings_title": null, "publisher": "", "title": "ACS applied materials & interfaces", "volume": "9", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Au-Protected Ag Core/Satellite Nanoassemblies for Excellent Extra-/Intracellular Surface-Enhanced Raman Scattering Activity.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Insulin triggers an extensive signaling cascade to coordinate adipocyte glucose metabolism. It is considered that the major role of insulin is to provide anabolic substrates by activating GLUT4-dependent glucose uptake. However, insulin stimulates phosphorylation of many metabolic proteins. To examine the implications of this on glucose metabolism, we performed dynamic tracer metabolomics in cultured adipocytes treated with insulin. Temporal analysis of metabolite concentrations and tracer labeling revealed rapid and distinct changes in glucose metabolism, favoring specific glycolytic branch points and pyruvate anaplerosis. Integrating dynamic metabolomics and phosphoproteomics data revealed that insulin-dependent phosphorylation of anabolic enzymes occurred prior to substrate accumulation. Indeed, glycogen synthesis was activated independently of glucose supply. We refer to this phenomenon as metabolic priming, whereby insulin signaling creates a demand-driven system to \"pull\" glucose into specific anabolic pathways. This complements the supply-driven regulation of anabolism by substrate accumulation and highlights an additional role for insulin action in adipocyte glucose metabolism.", "classifications": [ { "id": "Kuroda", "label": "Group Kuroda", "parent": "Kuroda", "type": "group" }, { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "James R.", "last_name": "Krycer", "name": null }, { "creator_type": "author", "first_name": "Katsuyuki", "last_name": "Yugi", "name": null }, { "creator_type": "author", "first_name": "Akiyoshi", "last_name": "Hirayama", "name": null }, { "creator_type": "author", "first_name": "Daniel J.", "last_name": "Fazakerley", "name": null }, { "creator_type": "author", "first_name": "Lake-Ee", "last_name": "Quek", "name": null }, { "creator_type": "author", "first_name": "Richard", "last_name": "Scalzo", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Ohno", "name": null }, { "creator_type": "author", "first_name": "Mark P.", "last_name": "Hodson", "name": null }, { "creator_type": "author", "first_name": "Satsuki", "last_name": "Ikeda", "name": null }, { "creator_type": "author", "first_name": "Futaba", "last_name": "Shoji", "name": null }, { "creator_type": "author", "first_name": "Kumi", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Westa", "last_name": "Domanova", "name": null }, { "creator_type": "author", "first_name": "Benjamin L.", "last_name": "Parker", "name": null }, { "creator_type": "author", "first_name": "Marin E.", "last_name": "Nelson", "name": null }, { "creator_type": "author", "first_name": "Sean J.", "last_name": "Humphrey", "name": null }, { "creator_type": "author", "first_name": "Nigel", "last_name": "Turner", "name": null }, { "creator_type": "author", "first_name": "Kyle L.", "last_name": "Hoehn", "name": null }, { "creator_type": "author", "first_name": "Gregory J.", "last_name": "Cooney", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Kuroda", "name": null }, { "creator_type": "author", "first_name": "David E.", "last_name": "James", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.celrep.2017.11.085" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "29262332" } }, "mesh": [ { "descriptor": "3T3 Cells", "descriptor_ui": "D016475", "major_topic": false }, { "descriptor": "Adipocytes", "descriptor_ui": "D017667", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Glucose", "descriptor_ui": "D005947", "major_topic": false }, { "descriptor": "Insulin", "descriptor_ui": "D007328", "major_topic": false }, { "descriptor": "Metabolome", "descriptor_ui": "D055442", "major_topic": true }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Dec 19", "date_precision": "day", "issue": "12", "normalized_date": "2017-12-19", "pages": "3536-3547", "proceedings_title": null, "publisher": "", "title": "Cell reports", "volume": "21", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Dynamic Metabolomics Reveals that Insulin Primes the Adipocyte for Glucose Metabolism.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Reprogramming of cellular identity using exogenous expression of transcription factors (TFs) is a powerful and exciting tool for tissue engineering, disease modeling, and regenerative medicine. However, generation of desired cell types using this approach is often plagued by inefficiency, slow conversion, and an inability to produce mature functional cells. Here, we show that expression of constitutively active SMAD2/3 significantly improves the efficiency of induced pluripotent stem cell (iPSC) generation by the Yamanaka factors. Mechanistically, SMAD3 interacts with reprogramming factors and co-activators and co-occupies OCT4 target loci during reprogramming. Unexpectedly, active SMAD2/3 also markedly enhances three other TF-mediated direct reprogramming conversions, from B cells to macrophages, myoblasts to adipocytes, and human fibroblasts to neurons, highlighting broad and general roles for SMAD2/3 as cell-reprogramming potentiators. Our results suggest that co-expression of active SMAD2/3 could enhance multiple types of TF-based cell identity conversion and therefore be a powerful tool for cellular engineering.", "classifications": [ { "id": "Yusa", "label": "Group Yusa", "parent": "Eiraku", "type": "group" }, { "id": "Eiraku", "label": "Team Eiraku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Tyson", "last_name": "Ruetz", "name": null }, { "creator_type": "author", "first_name": "Ulrich", "last_name": "Pfisterer", "name": null }, { "creator_type": "author", "first_name": "Bruno", "last_name": "Di Stefano", "name": null }, { "creator_type": "author", "first_name": "James", "last_name": "Ashmore", "name": null }, { "creator_type": "author", "first_name": "Meryam", "last_name": "Beniazza", "name": null }, { "creator_type": "author", "first_name": "Tian V.", "last_name": "Tian", "name": null }, { "creator_type": "author", "first_name": "Daniel F.", "last_name": "Kaemena", "name": null }, { "creator_type": "author", "first_name": "Luca", "last_name": "Tosti", "name": null }, { "creator_type": "author", "first_name": "Wenfang", "last_name": "Tan", "name": null }, { "creator_type": "author", "first_name": "Jonathan R.", "last_name": "Manning", "name": null }, { "creator_type": "author", "first_name": "Eleni", "last_name": "Chantzoura", "name": null }, { "creator_type": "author", "first_name": "Daniella Rylander", "last_name": "Ottosson", "name": null }, { "creator_type": "author", "first_name": "Samuel", "last_name": "Collombet", "name": null }, { "creator_type": "author", "first_name": "Anna", "last_name": "Johnsson", "name": null }, { "creator_type": "author", "first_name": "Erez", "last_name": "Cohen", "name": null }, { "creator_type": "author", "first_name": "Kosuke", "last_name": "Yusa", "name": null }, { "creator_type": "author", "first_name": "Sten", "last_name": "Linnarsson", "name": null }, { "creator_type": "author", "first_name": "Thomas", "last_name": "Graf", "name": null }, { "creator_type": "author", "first_name": "Malin", "last_name": "Parmar", "name": null }, { "creator_type": "author", "first_name": "Keisuke", "last_name": "Kaji", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.stem.2017.10.013" }, "pmcid": { "normalized": "PMC5732323" }, "pmid": { "normalized": "29174331" } }, "mesh": [ { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "Cellular Reprogramming", "descriptor_ui": "D065150", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Induced Pluripotent Stem Cells", "descriptor_ui": "D057026", "major_topic": false }, { "descriptor": "Smad2 Protein", "descriptor_ui": "D051899", "major_topic": false }, { "descriptor": "Smad3 Protein", "descriptor_ui": "D051900", "major_topic": false }, { "descriptor": "Transcription Factors", "descriptor_ui": "D014157", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Dec 7", "date_precision": "day", "issue": "6", "normalized_date": "2017-12-07", "pages": "791-805.e9", "proceedings_title": null, "publisher": "", "title": "Cell stem cell", "volume": "21", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Constitutively Active SMAD2/3 Are Broad-Scope Potentiators of Transcription-Factor-Mediated Cellular Reprogramming.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Mitral and tufted (M/T) cells in the olfactory bulb produce rich temporal patterns of activity in response to different odors. However, it remains unknown how these temporal patterns are generated and how they are utilized in olfaction. Here we show that temporal patterning effectively discriminates between the two sensory modalities detected by olfactory sensory neurons (OSNs): odor and airflow-driven mechanical signals. Sniff-induced mechanosensation generates glomerulus-specific oscillatory activity in M/T cells, whose phase was invariant across airflow speed. In contrast, odor stimulation caused phase shifts (phase coding). We also found that odor-evoked phase shifts are concentration invariant and stable across multiple sniff cycles, contrary to the labile nature of rate coding. The loss of oscillatory mechanosensation impaired the precision and stability of phase coding, demonstrating its role in olfaction. We propose that phase, not rate, coding is a robust encoding strategy of odor identity and is ensured by airflow-induced mechanosensation in OSNs.", "classifications": [ { "id": "Imai", "label": "Group Imai", "parent": "Enomoto", "type": "group" }, { "id": "Enomoto", "label": "Team Enomoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Ryo", "last_name": "Iwata", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Kiyonari", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Imai", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.neuron.2017.11.008" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "29216451" } }, "mesh": [ { "descriptor": "Absorptiometry, Photon", "descriptor_ui": "D015502", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Behavior, Animal", "descriptor_ui": "D001522", "major_topic": false }, { "descriptor": "Immunohistochemistry", "descriptor_ui": "D007150", "major_topic": false }, { "descriptor": "Mechanotransduction, Cellular", "descriptor_ui": "D040542", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Neuroimaging", "descriptor_ui": "D059906", "major_topic": false }, { "descriptor": "Odorants", "descriptor_ui": "D009812", "major_topic": false }, { "descriptor": "Olfactory Bulb", "descriptor_ui": "D009830", "major_topic": false }, { "descriptor": "Olfactory Pathways", "descriptor_ui": "D009833", "major_topic": false }, { "descriptor": "Olfactory Receptor Neurons", "descriptor_ui": "D018034", "major_topic": false }, { "descriptor": "Smell", "descriptor_ui": "D012903", "major_topic": false }, { "descriptor": "Tracheotomy", "descriptor_ui": "D014140", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Dec 6", "date_precision": "day", "issue": "5", "normalized_date": "2017-12-06", "pages": "1139-1152.e7", "proceedings_title": null, "publisher": "", "title": "Neuron", "volume": "96", "year": 2017 }, "ssbd": { "database": [ "ssbd-database-000066" ], "repository": [ "ssbd-repos-000066" ] }, "title": "Mechanosensory-Based Phase Coding of Odor Identity in the Olfactory Bulb.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Single transcription factors (TFs) regulate multiple developmental pathways, but the underlying mechanisms remain unclear. Here, we quantitatively characterized the genome-wide occupancy profiles of BLIMP1, a key transcriptional regulator for diverse developmental processes, during the development of three germ-layer derivatives (photoreceptor precursors, embryonic intestinal epithelium and plasmablasts) and the germ cell lineage (primordial germ cells). We identified BLIMP1-binding sites shared among multiple developmental processes, and such sites were highly occupied by BLIMP1 with a stringent recognition motif and were located predominantly in promoter proximities. A subset of bindings common to all the lineages exhibited a new, strong recognition sequence, a GGGAAA repeat. Paradoxically, however, the shared/common bindings had only a slight impact on the associated gene expression. In contrast, BLIMP1 occupied more distal sites in a cell type-specific manner; despite lower occupancy and flexible sequence recognitions, such bindings contributed effectively to the repression of the associated genes. Recognition motifs of other key TFs in BLIMP1-binding sites had little impact on the expression-level changes. These findings suggest that the shared/common sites might serve as potential reservoirs of BLIMP1 that functions at the specific sites, providing the foundation for a unified understanding of the genome regulation by BLIMP1, and, possibly, TFs in general.", "classifications": [ { "id": "Yamamoto", "label": "Group Yamamoto", "parent": "Toyoshima", "type": "group" }, { "id": "Toyoshima", "label": "Team Toyoshima", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Tadahiro", "last_name": "Mitani", "name": null }, { "creator_type": "author", "first_name": "Yukihiro", "last_name": "Yabuta", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Ohta", "name": null }, { "creator_type": "author", "first_name": "Tomonori", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Chika", "last_name": "Yamashiro", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Mitinori", "last_name": "Saitou", "name": null }, { "creator_type": "author", "first_name": "Kazuki", "last_name": "Kurimoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1093/nar/gkx798" }, "pmcid": { "normalized": "PMC5716175" }, "pmid": { "normalized": "28981894" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Binding Sites", "descriptor_ui": "D001665", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "DNA", "descriptor_ui": "D004247", "major_topic": false }, { "descriptor": "Embryo, Mammalian", "descriptor_ui": "D004622", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Gene Expression Regulation, Developmental", "descriptor_ui": "D018507", "major_topic": true }, { "descriptor": "Gene Knock-In Techniques", "descriptor_ui": "D055879", "major_topic": false }, { "descriptor": "Genome", "descriptor_ui": "D016678", "major_topic": false }, { "descriptor": "Germ Cells", "descriptor_ui": "D005854", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Nucleotide Motifs", "descriptor_ui": "D059372", "major_topic": false }, { "descriptor": "Positive Regulatory Domain I-Binding Factor 1", "descriptor_ui": "D000074462", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Dec 1", "date_precision": "day", "issue": "21", "normalized_date": "2017-12-01", "pages": "12152-12169", "proceedings_title": null, "publisher": "", "title": "Nucleic acids research", "volume": "45", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Principles for the regulation of multiple developmental pathways by a versatile transcriptional factor, BLIMP1.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "This work describes a practical and efficient method for synthesizing a diverse array of perfluoroalkylated amines, including N-heterocycles, to afford perfluoroalkylated chemical libraries as potential sources of drug candidates, agrochemicals, and probe molecules for chemical-biology research. Perfluoro acid anhydrides, which are commonly used in organic synthesis, were employed as a perfluoroalkyl source for intramolecular amino- and carbo-perfluoroalkylations of aminoalkenes, affording perfluoroalkylated N-heterocycles, including: aziridines, pyrrolidines, benzothiazinane dioxides, indolines, and hydroisoquinolinones. Diacyl peroxides were generated in situ from the perfluoro acid anhydrides with urea.H(2)O(2), and allowed to react with aminoalkenes in the presence of copper catalyst to control the product selectivity between amino- and carbo-perfluoroalkylations. To illustrate the synthetic utility of bench-stable trifluoromethylated aziridine, which was prepared on a gram scale, we used it to synthesize a wide variety of trifluoromethylated amines including complex molecules, such as trifluoromethylated tetrahydroharmine and spiroindolone. A mechanistic study of the role of the copper catalyst in the aminotrifluoromethylation of allylamine suggested that Cu(I) accelerates CF(3) radical formation via decomposition of diacyl peroxide, which appears to be the turnover-limiting step, while Cu(II) controls the product selectivity.", "classifications": [ { "id": "Sodeoka", "label": "Group Sodeoka", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Shintaro", "last_name": "Kawamura", "name": null }, { "creator_type": "author", "first_name": "Kento", "last_name": "Dosei", "name": null }, { "creator_type": "author", "first_name": "Elena", "last_name": "Valverde", "name": null }, { "creator_type": "author", "first_name": "Kiminori", "last_name": "Ushida", "name": null }, { "creator_type": "author", "first_name": "Mikiko", "last_name": "Sodeoka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/acs.joc.7b02307" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "29052416" } }, "mesh": [], "publication": { "conference_name": null, "date": "2017 Dec 1", "date_precision": "day", "issue": "23", "normalized_date": "2017-12-01", "pages": "12539-12553", "proceedings_title": null, "publisher": "", "title": "The Journal of organic chemistry", "volume": "82", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "N-Heterocycle-Forming Amino/Carboperfluoroalkylations of Aminoalkenes by Using Perfluoro Acid Anhydrides: Mechanistic Studies and Applications Directed Toward Perfluoroalkylated Compound Libraries.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Normal epithelial cells are stably connected to each other via the apical junctional complex (AJC). AJCs, however, tend to be disrupted during tumor progression, and this process is implicated in cancer dissemination. Here, using colon carcinoma cells that fail to form AJCs, we investigated molecular defects behind this failure through a search for chemical compounds that could restore AJCs, and found that microtubule-polymerization inhibitors (MTIs) were effective. MTIs activated GEF-H1/RhoA signaling, causing actomyosin contraction at the apical cortex. This contraction transmitted force to the cadherin-catenin complex, resulting in a mechanosensitive recruitment of vinculin to cell junctions. This process, in turn, recruited PDZ-RhoGEF to the junctions, leading to the RhoA/ROCK/LIM kinase/cofilin-dependent stabilization of the junctions. RhoGAP depletion mimicked these MTI-mediated processes. Cells that normally organize AJCs did not show such MTI/RhoA sensitivity. Thus, advanced carcinoma cells require elevated RhoA activity for establishing robust junctions, which triggers tension-sensitive reorganization of actin/adhesion regulators.", "classifications": [ { "id": "Okuda", "label": "Group Okuda", "parent": "Imayoshi", "type": "group" }, { "id": "Imayoshi", "label": "Team Imayoshi", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Shoko", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Satoru", "last_name": "Okuda", "name": null }, { "creator_type": "author", "first_name": "Masako", "last_name": "Abe", "name": null }, { "creator_type": "author", "first_name": "Mari", "last_name": "Fujimoto", "name": null }, { "creator_type": "author", "first_name": "Tetsuo", "last_name": "Onuki", "name": null }, { "creator_type": "author", "first_name": "Tamako", "last_name": "Nishimura", "name": null }, { "creator_type": "author", "first_name": "Masatoshi", "last_name": "Takeichi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41467-017-01945-y" }, "pmcid": { "normalized": "PMC5705652" }, "pmid": { "normalized": "29184140" } }, "mesh": [ { "descriptor": "Actin Cytoskeleton", "descriptor_ui": "D008841", "major_topic": false }, { "descriptor": "Actin Depolymerizing Factors", "descriptor_ui": "D051339", "major_topic": false }, { "descriptor": "Actins", "descriptor_ui": "D000199", "major_topic": false }, { "descriptor": "Actomyosin", "descriptor_ui": "D000205", "major_topic": false }, { "descriptor": "Adherens Junctions", "descriptor_ui": "D022005", "major_topic": false }, { "descriptor": "Biomechanical Phenomena", "descriptor_ui": "D001696", "major_topic": false }, { "descriptor": "Caco-2 Cells", "descriptor_ui": "D018938", "major_topic": false }, { "descriptor": "Cadherins", "descriptor_ui": "D015820", "major_topic": false }, { "descriptor": "Cell Adhesion", "descriptor_ui": "D002448", "major_topic": false }, { "descriptor": "Cell Adhesion Molecules", "descriptor_ui": "D015815", "major_topic": false }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Colonic Neoplasms", "descriptor_ui": "D003110", "major_topic": false }, { "descriptor": "Cytoskeletal Proteins", "descriptor_ui": "D003598", "major_topic": false }, { "descriptor": "Epithelial Cells", "descriptor_ui": "D004847", "major_topic": false }, { "descriptor": "Guanine Nucleotide Exchange Factors", "descriptor_ui": "D020662", "major_topic": false }, { "descriptor": "HT29 Cells", "descriptor_ui": "D019073", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Intercellular Junctions", "descriptor_ui": "D007365", "major_topic": false }, { "descriptor": "Lim Kinases", "descriptor_ui": "D054461", "major_topic": false }, { "descriptor": "Microtubules", "descriptor_ui": "D008870", "major_topic": false }, { "descriptor": "Myosin Type II", "descriptor_ui": "D024462", "major_topic": false }, { "descriptor": "Nocodazole", "descriptor_ui": "D015739", "major_topic": false }, { "descriptor": "rho-Associated Kinases", "descriptor_ui": "D054460", "major_topic": false }, { "descriptor": "rhoA GTP-Binding Protein", "descriptor_ui": "D020742", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Vinculin", "descriptor_ui": "D016596", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Nov 28", "date_precision": "day", "issue": "1", "normalized_date": "2017-11-28", "pages": "1834", "proceedings_title": null, "publisher": "", "title": "Nature communications", "volume": "8", "year": 2017 }, "ssbd": { "database": [ "ssbd-database-000084" ], "repository": [ "ssbd-repos-000084" ] }, "title": "Induced cortical tension restores functional junctions in adhesion-defective carcinoma cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Cell migration plays a pivotal role in morphogenetic and pathogenetic processes. To achieve directional migration, cells must establish a front-to-rear axis of polarity. Here we show that components of the cadherin-catenin complex function to stabilize this front-rear polarity. Neural crest and glioblastoma cells undergo directional migration in vivo or in vitro. During this process, alphaE-catenin accumulated at lamellipodial membranes and then moved toward the rear with the support of a tyrosine-phosphorylated beta-catenin. This relocating alphaE-catenin bound to p115RhoGEF, leading to gathering of active RhoA in front of the nucleus where myosin-IIB arcs assemble. When catenins or p115RhoGEF were removed, cells lost the polarized myosin-IIB assembly, as well as the capability for directional movement. These results suggest that, apart from its well-known function in cell adhesion, the beta-catenin/alphaE-catenin complex regulates directional cell migration by restricting active RhoA to perinuclear regions and controlling myosin-IIB dynamics at these sites.", "classifications": [ { "id": "Enomoto", "label": "Group Enomoto", "parent": "Enomoto", "type": "group" }, { "id": "Enomoto", "label": "Team Enomoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Vassil", "last_name": "Vassilev", "name": null }, { "creator_type": "author", "first_name": "Anna", "last_name": "Platek", "name": null }, { "creator_type": "author", "first_name": "Sylvain", "last_name": "Hiver", "name": null }, { "creator_type": "author", "first_name": "Hideki", "last_name": "Enomoto", "name": null }, { "creator_type": "author", "first_name": "Masatoshi", "last_name": "Takeichi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.devcel.2017.10.014" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "29103954" } }, "mesh": [ { "descriptor": "Actins", "descriptor_ui": "D000199", "major_topic": false }, { "descriptor": "alpha Catenin", "descriptor_ui": "D051178", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cadherins", "descriptor_ui": "D015820", "major_topic": false }, { "descriptor": "Catenins", "descriptor_ui": "D051177", "major_topic": false }, { "descriptor": "Cell Membrane", "descriptor_ui": "D002462", "major_topic": false }, { "descriptor": "Cell Movement", "descriptor_ui": "D002465", "major_topic": false }, { "descriptor": "Cell Nucleus", "descriptor_ui": "D002467", "major_topic": false }, { "descriptor": "Cell Polarity", "descriptor_ui": "D016764", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Neural Crest", "descriptor_ui": "D009432", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Nov 20", "date_precision": "day", "issue": "4", "normalized_date": "2017-11-20", "pages": "463-479.e5", "proceedings_title": null, "publisher": "", "title": "Developmental cell", "volume": "43", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Catenins Steer Cell Migration via Stabilization of Front-Rear Polarity.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Higher-order chromatin organization controls transcriptional programs that govern cell properties and functions. In order for pluripotent stem cells (PSCs) to appropriately respond to differentiation signals, developmental gene loci should be structurally and spatially regulated to be readily available for immediate transcription, even though these genes are hardly expressed in PSCs. Here, we show that both chromatin interaction profiles and nuclear positions at developmental gene loci differ between human somatic cells and hPSCs, and that changes in the chromatin interactions are closely related to the nuclear repositioning. Moreover, we also demonstrate that developmental gene loci, which have bivalent histone modifications, tend to colocalize in PSCs. Furthermore, this colocalization requires PRC1, PRC2, and TrxG complexes, which are essential regulatory factors for the maintenance of transcriptionally poised developmental genes. Our results indicate that higher-order chromatin regulation may be an integral part of the differentiation capacity that defines pluripotency.", "classifications": [ { "id": "Yamamoto", "label": "Group Yamamoto", "parent": "Toyoshima", "type": "group" }, { "id": "Toyoshima", "label": "Team Toyoshima", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Hiroki", "last_name": "Ikeda", "name": null }, { "creator_type": "author", "first_name": "Masamitsu", "last_name": "Sone", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Yamanaka", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Yamamoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41467-017-01679-x" }, "pmcid": { "normalized": "PMC5696376" }, "pmid": { "normalized": "29158493" } }, "mesh": [ { "descriptor": "Cell Cycle Proteins", "descriptor_ui": "D018797", "major_topic": false }, { "descriptor": "Chromatin", "descriptor_ui": "D002843", "major_topic": false }, { "descriptor": "Gene Expression Regulation, Developmental", "descriptor_ui": "D018507", "major_topic": false }, { "descriptor": "Genes, Developmental", "descriptor_ui": "D050437", "major_topic": false }, { "descriptor": "Genetic Loci", "descriptor_ui": "D056426", "major_topic": true }, { "descriptor": "Histone Code", "descriptor_ui": "D042421", "major_topic": false }, { "descriptor": "Histones", "descriptor_ui": "D006657", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Methylation", "descriptor_ui": "D008745", "major_topic": false }, { "descriptor": "Pluripotent Stem Cells", "descriptor_ui": "D039904", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Nov 20", "date_precision": "day", "issue": "1", "normalized_date": "2017-11-20", "pages": "1616", "proceedings_title": null, "publisher": "", "title": "Nature communications", "volume": "8", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Structural and spatial chromatin features at developmental gene loci in human pluripotent stem cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "There is a dearth of knowledge about the pathogenesis of premalignant lung lesions, especially for atypical adenomatous hyperplasia (AAH), the only known precursor for the major lung cancer subtype adenocarcinoma (LUAD). In this study, we performed deep DNA and RNA sequencing analyses of a set of AAH, LUAD, and normal tissues. Somatic BRAF variants were found in AAHs from 5 of 22 (23%) patients, 4 of 5 of whom had matched LUAD with driver EGFR mutations. KRAS mutations were present in AAHs from 4 of 22 (18%) of patients. KRAS mutations in AAH were only found in ever-smokers and were exclusive to BRAF-mutant cases. Integrative analysis revealed profiles expressed in KRAS-mutant cases (UBE2C, REL) and BRAF-mutant cases (MAX) of AAH, or common to both sets of cases (suppressed AXL). Gene sets associated with suppressed antitumor (Th1; IL12A, GZMB) and elevated protumor (CCR2, CTLA-4) immune signaling were enriched in AAH development and progression. Our results reveal potentially divergent BRAF or KRAS pathways in AAH as well as immune dysregulation in the pathogenesis of this premalignant lung lesion. Cancer Res; 77(22); 6119-30. ©2017 AACR.", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Smruthy", "last_name": "Sivakumar", "name": null }, { "creator_type": "author", "first_name": "F. Anthony San", "last_name": "Lucas", "name": null }, { "creator_type": "author", "first_name": "Tina L.", "last_name": "McDowell", "name": null }, { "creator_type": "author", "first_name": "Wenhua", "last_name": "Lang", "name": null }, { "creator_type": "author", "first_name": "Li", "last_name": "Xu", "name": null }, { "creator_type": "author", "first_name": "Junya", "last_name": "Fujimoto", "name": null }, { "creator_type": "author", "first_name": "Jianjun", "last_name": "Zhang", "name": null }, { "creator_type": "author", "first_name": "P. Andrew", "last_name": "Futreal", "name": null }, { "creator_type": "author", "first_name": "Junya", "last_name": "Fukuoka", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null }, { "creator_type": "author", "first_name": "Steven M.", "last_name": "Dubinett", "name": null }, { "creator_type": "author", "first_name": "Avrum E.", "last_name": "Spira", "name": null }, { "creator_type": "author", "first_name": "Jerry", "last_name": "Fowler", "name": null }, { "creator_type": "author", "first_name": "Ernest T.", "last_name": "Hawk", "name": null }, { "creator_type": "author", "first_name": "Ignacio I.", "last_name": "Wistuba", "name": null }, { "creator_type": "author", "first_name": "Paul", "last_name": "Scheet", "name": null }, { "creator_type": "author", "first_name": "Humam", "last_name": "Kadara", "name": null } ], "identifiers": { "doi": { "normalized": "10.1158/0008-5472.can-17-1605" }, "pmcid": { "normalized": "PMC5774855" }, "pmid": { "normalized": "28951454" } }, "mesh": [ { "descriptor": "Adenocarcinoma", "descriptor_ui": "D000230", "major_topic": false }, { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Disease Progression", "descriptor_ui": "D018450", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Gene Expression Profiling", "descriptor_ui": "D020869", "major_topic": false }, { "descriptor": "Genomics", "descriptor_ui": "D023281", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Hyperplasia", "descriptor_ui": "D006965", "major_topic": false }, { "descriptor": "Lung", "descriptor_ui": "D008168", "major_topic": false }, { "descriptor": "Lung Neoplasms", "descriptor_ui": "D008175", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": false }, { "descriptor": "Precancerous Conditions", "descriptor_ui": "D011230", "major_topic": false }, { "descriptor": "Proto-Oncogene Proteins B-raf", "descriptor_ui": "D048493", "major_topic": false }, { "descriptor": "Proto-Oncogene Proteins p21(ras)", "descriptor_ui": "D016283", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Nov 15", "date_precision": "day", "issue": "22", "normalized_date": "2017-11-15", "pages": "6119-6130", "proceedings_title": null, "publisher": "", "title": "Cancer research", "volume": "77", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Genomic Landscape of Atypical Adenomatous Hyperplasia Reveals Divergent Modes to Lung Adenocarcinoma.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The de novo L-cysteine biosynthetic pathway is critical for the growth, antioxidative stress defenses, and pathogenesis of bacterial and protozoan pathogens, such as Salmonella typhimurium and Entamoeba histolytica. This pathway involves two key enzymes, serine acetyltransferase (SAT) and cysteine synthase (CS), which are absent in mammals and therefore represent rational drug targets. The human parasite E. histolytica possesses three SAT and CS isozymes; however, the specific roles of individual isoforms and significance of such apparent redundancy remains unclear. In the present study, we generated E. histolytica cell lines in which CS and SAT expression was knocked down by transcriptional gene silencing. The strain in which CS1, 2 and 3 were simultaneously silenced and the SAT3 gene-silenced strain showed impaired growth when cultured in a cysteine lacking BI-S-33 medium, whereas silencing of SAT1 and SAT2 had no effects on growth. Combined transcriptomic and metabolomic analyses revealed that, CS and SAT3 are involved in S-methylcysteine/cysteine synthesis. Furthermore, silencing of the CS1-3 or SAT3 caused upregulation of various iron-sulfur flavoprotein genes. Taken together, these results provide the first direct evidence of the biological importance of SAT3 and CS isoforms in E. histolytica and justify the exploitation of these enzymes as potential drug targets.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Ghulam", "last_name": "Jeelani", "name": null }, { "creator_type": "author", "first_name": "Dan", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Nozaki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41598-017-15923-3" }, "pmcid": { "normalized": "PMC5688106" }, "pmid": { "normalized": "29142277" } }, "mesh": [ { "descriptor": "Amino Acid Sequence", "descriptor_ui": "D000595", "major_topic": false }, { "descriptor": "Biosynthetic Pathways", "descriptor_ui": "D053898", "major_topic": false }, { "descriptor": "Cysteine", "descriptor_ui": "D003545", "major_topic": false }, { "descriptor": "Cysteine Synthase", "descriptor_ui": "D003547", "major_topic": false }, { "descriptor": "Entamoeba histolytica", "descriptor_ui": "D004748", "major_topic": false }, { "descriptor": "Gene Expression Profiling", "descriptor_ui": "D020869", "major_topic": false }, { "descriptor": "Protozoan Proteins", "descriptor_ui": "D015800", "major_topic": false }, { "descriptor": "Serine O-Acetyltransferase", "descriptor_ui": "D051050", "major_topic": false }, { "descriptor": "Substrate Specificity", "descriptor_ui": "D013379", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Nov 15", "date_precision": "day", "issue": "1", "normalized_date": "2017-11-15", "pages": "15649", "proceedings_title": null, "publisher": "", "title": "Scientific reports", "volume": "7", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Genetic, metabolomic and transcriptomic analyses of the de novo L-cysteine biosynthetic pathway in the enteric protozoan parasite Entamoeba histolytica.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "[Zn(2)(FDC)(2)(bpy)] (LMOF-202) and [Zn(2)(OFDC)(2)(bpy)] (LMOF-201) (FDC: fluorene-2,7-dicarboxylate, OFDC: 9-fluorenone-2,7-dicarboxylate, bpy: 4,4'-bipyridine) have interpenetrated isostructures. However, their gas sorption behaviors indicate that LMOF-202 is rigid, whereas LMOF-201 is flexible. We found that the structural flexibility of LMOF-201 was due to the addition of only one oxygen atom into the ligand.", "classifications": [ { "id": "Hijikata", "label": "Group Hijikata", "parent": "Tsuchiya", "type": "group" }, { "id": "Tsuchiya", "label": "Team Tsuchiya", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yunsheng", "last_name": "Ma", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Harada", "name": null }, { "creator_type": "author", "first_name": "Akihiro", "last_name": "Hori", "name": null }, { "creator_type": "author", "first_name": "Yuh", "last_name": "Hijikata", "name": null }, { "creator_type": "author", "first_name": "Liangchun", "last_name": "Li", "name": null }, { "creator_type": "author", "first_name": "Ryotaro", "last_name": "Matsuda", "name": null } ], "identifiers": { "doi": { "normalized": "10.1039/c7dt03338a" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "29072736" } }, "mesh": [], "publication": { "conference_name": null, "date": "2017 Nov 14", "date_precision": "day", "issue": "44", "normalized_date": "2017-11-14", "pages": "15200-15203", "proceedings_title": null, "publisher": "", "title": "Dalton transactions (Cambridge, England : 2003)", "volume": "46", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Tuning the flexibility of interpenetrated frameworks by a small difference in the fluorene moiety.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Most of the enteric nervous system derives from the \"vagal\" neural crest, lying at the level of somites 1-7, which invades the digestive tract rostro-caudally from the foregut to the hindgut. Little is known about the initial phase of this colonization, which brings enteric precursors into the foregut. Here we show that the \"vagal crest\" subsumes two populations of enteric precursors with contrasted origins, initial modes of migration, and destinations. Crest cells adjacent to somites 1 and 2 produce Schwann cell precursors that colonize the vagus nerve, which in turn guides them into the esophagus and stomach. Crest cells adjacent to somites 3-7 belong to the crest streams contributing to sympathetic chains: they migrate ventrally, seed the sympathetic chains, and colonize the entire digestive tract thence. Accordingly, enteric ganglia, like sympathetic ones, are atrophic when deprived of signaling through the tyrosine kinase receptor ErbB3, while half of the esophageal ganglia require, like parasympathetic ones, the nerve-associated form of the ErbB3 ligand, Neuregulin-1. These dependencies might bear relevance to Hirschsprung disease, with which alleles of Neuregulin-1 are associated.", "classifications": [ { "id": "Enomoto", "label": "Group Enomoto", "parent": "Enomoto", "type": "group" }, { "id": "Enomoto", "label": "Team Enomoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Isabel", "last_name": "Espinosa-Medina", "name": null }, { "creator_type": "author", "first_name": "Ben", "last_name": "Jevans", "name": null }, { "creator_type": "author", "first_name": "Franck", "last_name": "Boismoreau", "name": null }, { "creator_type": "author", "first_name": "Zoubida", "last_name": "Chettouh", "name": null }, { "creator_type": "author", "first_name": "Hideki", "last_name": "Enomoto", "name": null }, { "creator_type": "author", "first_name": "Thomas", "last_name": "Muller", "name": null }, { "creator_type": "author", "first_name": "Carmen", "last_name": "Birchmeier", "name": null }, { "creator_type": "author", "first_name": "Alan J.", "last_name": "Burns", "name": null }, { "creator_type": "author", "first_name": "Jean-Francois", "last_name": "Brunet", "name": null } ], "identifiers": { "doi": { "normalized": "10.1073/pnas.1710308114" }, "pmcid": { "normalized": "PMC5692562" }, "pmid": { "normalized": "29078343" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Chick Embryo", "descriptor_ui": "D002642", "major_topic": false }, { "descriptor": "Enteric Nervous System", "descriptor_ui": "D017615", "major_topic": false }, { "descriptor": "Ganglia, Sympathetic", "descriptor_ui": "D005728", "major_topic": false }, { "descriptor": "Gastrointestinal Tract", "descriptor_ui": "D041981", "major_topic": false }, { "descriptor": "Hirschsprung Disease", "descriptor_ui": "D006627", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Neural Crest", "descriptor_ui": "D009432", "major_topic": false }, { "descriptor": "Neuregulin-1", "descriptor_ui": "D020890", "major_topic": false }, { "descriptor": "Neurogenesis", "descriptor_ui": "D055495", "major_topic": false }, { "descriptor": "Receptor, ErbB-3", "descriptor_ui": "D020893", "major_topic": false }, { "descriptor": "Schwann Cells", "descriptor_ui": "D012583", "major_topic": false }, { "descriptor": "Vagus Nerve", "descriptor_ui": "D014630", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Nov 7", "date_precision": "day", "issue": "45", "normalized_date": "2017-11-07", "pages": "11980-11985", "proceedings_title": null, "publisher": "", "title": "Proceedings of the National Academy of Sciences of the United States of America", "volume": "114", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Dual origin of enteric neurons in vagal Schwann cell precursors and the sympathetic neural crest.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Recent advances in self-organizing, 3-dimensional tissue cultures of embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) provided an in vitro model that recapitulates many aspects of the in vivo developmental steps. Using Rax-GFP-expressing ESCs, newly generated Six3(-/-) iPSCs, and conditional null Six3(delta/f);Rax-Cre ESCs, we identified Six3 repression of R-spondin 2 (Rspo2) as a required step during optic vesicle morphogenesis and neuroretina differentiation. We validated these results in vivo by showing that transient ectopic expression of Rspo2 in the anterior neural plate of transgenic mouse embryos was sufficient to inhibit neuroretina differentiation. Additionally, using a chimeric eye organoid assay, we determined that Six3 null cells exert a non-cell-autonomous repressive effect during optic vesicle formation and neuroretina differentiation. Our results further validate the organoid culture system as a reliable and fast alternative to identify and evaluate genes involved in eye morphogenesis and neuroretina differentiation in vivo.", "classifications": [ { "id": "Eiraku", "label": "Group Eiraku", "parent": "Eiraku", "type": "group" }, { "id": "Eiraku", "label": "Team Eiraku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Nozomu", "last_name": "Takata", "name": null }, { "creator_type": "author", "first_name": "Deepti", "last_name": "Abbey", "name": null }, { "creator_type": "author", "first_name": "Luciano", "last_name": "Fiore", "name": null }, { "creator_type": "author", "first_name": "Sandra", "last_name": "Acosta", "name": null }, { "creator_type": "author", "first_name": "Ruopeng", "last_name": "Feng", "name": null }, { "creator_type": "author", "first_name": "Hyea Jin", "last_name": "Gil", "name": null }, { "creator_type": "author", "first_name": "Alfonso", "last_name": "Lavado", "name": null }, { "creator_type": "author", "first_name": "Xin", "last_name": "Geng", "name": null }, { "creator_type": "author", "first_name": "Ashley", "last_name": "Interiano", "name": null }, { "creator_type": "author", "first_name": "Geoffrey", "last_name": "Neale", "name": null }, { "creator_type": "author", "first_name": "Mototsugu", "last_name": "Eiraku", "name": null }, { "creator_type": "author", "first_name": "Yoshiki", "last_name": "Sasai", "name": null }, { "creator_type": "author", "first_name": "Guillermo", "last_name": "Oliver", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.celrep.2017.10.041" }, "pmcid": { "normalized": "PMC5728169" }, "pmid": { "normalized": "29117559" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Axin Protein", "descriptor_ui": "D060466", "major_topic": false }, { "descriptor": "Cell Culture Techniques", "descriptor_ui": "D018929", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Embryo, Mammalian", "descriptor_ui": "D004622", "major_topic": false }, { "descriptor": "Embryonic Stem Cells", "descriptor_ui": "D053595", "major_topic": false }, { "descriptor": "Eye Proteins", "descriptor_ui": "D005136", "major_topic": false }, { "descriptor": "Homeobox Protein SIX3", "descriptor_ui": "D000097607", "major_topic": false }, { "descriptor": "Homeodomain Proteins", "descriptor_ui": "D018398", "major_topic": false }, { "descriptor": "In Situ Hybridization, Fluorescence", "descriptor_ui": "D017404", "major_topic": false }, { "descriptor": "Induced Pluripotent Stem Cells", "descriptor_ui": "D057026", "major_topic": false }, { "descriptor": "Intercellular Signaling Peptides and Proteins", "descriptor_ui": "D036341", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Transgenic", "descriptor_ui": "D008822", "major_topic": false }, { "descriptor": "Nerve Tissue Proteins", "descriptor_ui": "D009419", "major_topic": false }, { "descriptor": "Neural Plate", "descriptor_ui": "D054258", "major_topic": false }, { "descriptor": "Oligonucleotide Array Sequence Analysis", "descriptor_ui": "D020411", "major_topic": false }, { "descriptor": "R-Spondins", "descriptor_ui": "D000098907", "major_topic": false }, { "descriptor": "Retina", "descriptor_ui": "D012160", "major_topic": false }, { "descriptor": "SOXB1 Transcription Factors", "descriptor_ui": "D055748", "major_topic": false }, { "descriptor": "Thrombospondins", "descriptor_ui": "D019699", "major_topic": false }, { "descriptor": "Transcription Factors", "descriptor_ui": "D014157", "major_topic": false }, { "descriptor": "Wnt Proteins", "descriptor_ui": "D051153", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Nov 7", "date_precision": "day", "issue": "6", "normalized_date": "2017-11-07", "pages": "1534-1549", "proceedings_title": null, "publisher": "", "title": "Cell reports", "volume": "21", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "An Eye Organoid Approach Identifies Six3 Suppression of R-spondin 2 as a Critical Step in Mouse Neuroretina Differentiation.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The neuroectoderm is patterned along a rostral-caudal axis in response to localized factors in the embryo, but exactly how these factors act as positional information for this patterning is not yet fully understood. Here, using the self-organizing properties of mouse embryonic stem cell (ESC), we report that ESC-derived neuroectoderm self-generates a Six3(+) rostral and a Irx3(+) caudal bipolarized patterning. In this instance, localized Fgf signaling performs dual roles, as it regulates Six3(+) rostral polarization at an earlier stage and promotes Wnt signaling at a later stage. The Wnt signaling components are differentially expressed in the polarized tissues, leading to genome-wide Irx3(+) caudal-polarization signals. Surprisingly, differentially expressed Wnt agonists and antagonists have essential roles in orchestrating the formation of a balanced rostral-caudal neuroectoderm pattern. Together, our findings provide key processes for dynamic self-patterning and evidence that a temporally and locally regulated interaction between Fgf and Wnt signaling controls self-patterning in ESC-derived neuroectoderm.", "classifications": [ { "id": "Eiraku", "label": "Group Eiraku", "parent": "Eiraku", "type": "group" }, { "id": "Eiraku", "label": "Team Eiraku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Nozomu", "last_name": "Takata", "name": null }, { "creator_type": "author", "first_name": "Eriko", "last_name": "Sakakura", "name": null }, { "creator_type": "author", "first_name": "Mototsugu", "last_name": "Eiraku", "name": null }, { "creator_type": "author", "first_name": "Takeya", "last_name": "Kasukawa", "name": null }, { "creator_type": "author", "first_name": "Yoshiki", "last_name": "Sasai", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41467-017-01105-2" }, "pmcid": { "normalized": "PMC5673904" }, "pmid": { "normalized": "29109536" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Body Patterning", "descriptor_ui": "D019521", "major_topic": false }, { "descriptor": "Embryonic Stem Cells", "descriptor_ui": "D053595", "major_topic": false }, { "descriptor": "Eye Proteins", "descriptor_ui": "D005136", "major_topic": false }, { "descriptor": "Fibroblast Growth Factor 5", "descriptor_ui": "D051521", "major_topic": false }, { "descriptor": "Fibroblast Growth Factors", "descriptor_ui": "D005346", "major_topic": false }, { "descriptor": "Gene Expression Regulation, Developmental", "descriptor_ui": "D018507", "major_topic": false }, { "descriptor": "Homeobox Protein SIX3", "descriptor_ui": "D000097607", "major_topic": false }, { "descriptor": "Homeodomain Proteins", "descriptor_ui": "D018398", "major_topic": false }, { "descriptor": "Intercellular Signaling Peptides and Proteins", "descriptor_ui": "D036341", "major_topic": false }, { "descriptor": "Membrane Proteins", "descriptor_ui": "D008565", "major_topic": false }, { "descriptor": "Mice, Inbred ICR", "descriptor_ui": "D008813", "major_topic": false }, { "descriptor": "Mice, Transgenic", "descriptor_ui": "D008822", "major_topic": false }, { "descriptor": "Nerve Tissue Proteins", "descriptor_ui": "D009419", "major_topic": false }, { "descriptor": "Neural Plate", "descriptor_ui": "D054258", "major_topic": false }, { "descriptor": "Secreted Frizzled-Related Proteins", "descriptor_ui": "D000094742", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Transcription Factors", "descriptor_ui": "D014157", "major_topic": false }, { "descriptor": "Wnt Proteins", "descriptor_ui": "D051153", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Nov 7", "date_precision": "day", "issue": "1", "normalized_date": "2017-11-07", "pages": "1339", "proceedings_title": null, "publisher": "", "title": "Nature communications", "volume": "8", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Self-patterning of rostral-caudal neuroectoderm requires dual role of Fgf signaling for localized Wnt antagonism.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "We report direct observation of a spatial distribution of water molecules inside of a living cell using Raman images of the O-H stretching band of water. The O-H Raman intensity of the nucleus was higher than that of the cytoplasm, indicating that the water density is higher in the nucleus than that in the cytoplasm. The shape of the O-H stretching band of the nucleus differed from that of the cytoplasm but was similar to that of the balanced salt solution surrounding cells, indicating less crowded environments in the nucleus. The concentration of biomolecules having C-H bonds was also estimated to be lower in the nucleus than that in the cytoplasm. These results indicate that the nucleus is less crowded with biomolecules than the cytoplasm.", "classifications": [ { "id": "Nakabayashi", "label": "Group Nakabayashi", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Mizuki", "last_name": "Takeuchi", "name": null }, { "creator_type": "author", "first_name": "Shinji", "last_name": "Kajimoto", "name": null }, { "creator_type": "author", "first_name": "Takakazu", "last_name": "Nakabayashi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/acs.jpclett.7b02154" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "29022721" } }, "mesh": [ { "descriptor": "Cell Nucleus", "descriptor_ui": "D002467", "major_topic": false }, { "descriptor": "Cytoplasm", "descriptor_ui": "D003593", "major_topic": false }, { "descriptor": "Hydrogen Bonding", "descriptor_ui": "D006860", "major_topic": false }, { "descriptor": "Microscopy", "descriptor_ui": "D008853", "major_topic": false }, { "descriptor": "Spectrum Analysis, Raman", "descriptor_ui": "D013059", "major_topic": false }, { "descriptor": "Water", "descriptor_ui": "D014867", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Nov 2", "date_precision": "day", "issue": "21", "normalized_date": "2017-11-02", "pages": "5241-5245", "proceedings_title": null, "publisher": "", "title": "The journal of physical chemistry letters", "volume": "8", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Experimental Evaluation of the Density of Water in a Cell by Raman Microscopy.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Eukaryotic cells spend most of their life in interphase of the cell cycle. Understanding the rich diversity of metabolic and genomic regulation that occurs in interphase requires the demarcation of precise phase boundaries in situ. Here, we report the properties of two genetically encoded fluorescence sensors, Fucci(CA) and Fucci(SCA), which enable real-time monitoring of interphase and cell-cycle biology. We re-engineered the Cdt1-based sensor from the original Fucci system to respond to S phase-specific CUL4(Ddb1)-mediated ubiquitylation alone or in combination with SCF(Skp2)-mediated ubiquitylation. In cultured cells, Fucci(CA) produced a sharp triple color-distinct separation of G1, S, and G2, while Fucci(SCA) permitted a two-color readout of G1 and S/G2. Fucci(CA) applications included tracking the transient G1 phase of rapidly dividing mouse embryonic stem cells and identifying a window for UV-irradiation damage in S phase. These results show that Fucci(CA) is an essential tool for quantitative studies of interphase cell-cycle regulation.", "classifications": [ { "id": "Sawano", "label": "Group Sawano", "parent": "Shintaku", "type": "group" }, { "id": "Shintaku", "label": "Team Shintaku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Asako", "last_name": "Sakaue-Sawano", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Yo", "name": null }, { "creator_type": "author", "first_name": "Naoki", "last_name": "Komatsu", "name": null }, { "creator_type": "author", "first_name": "Toru", "last_name": "Hiratsuka", "name": null }, { "creator_type": "author", "first_name": "Takako", "last_name": "Kogure", "name": null }, { "creator_type": "author", "first_name": "Tetsushi", "last_name": "Hoshida", "name": null }, { "creator_type": "author", "first_name": "Naoki", "last_name": "Goshima", "name": null }, { "creator_type": "author", "first_name": "Michiyuki", "last_name": "Matsuda", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Miyoshi", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Miyawaki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.molcel.2017.10.001" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "29107535" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Cycle", "descriptor_ui": "D002453", "major_topic": false }, { "descriptor": "Cell Cycle Proteins", "descriptor_ui": "D018797", "major_topic": false }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Cullin Proteins", "descriptor_ui": "D044842", "major_topic": false }, { "descriptor": "Embryonic Stem Cells", "descriptor_ui": "D053595", "major_topic": false }, { "descriptor": "Fluorescent Dyes", "descriptor_ui": "D005456", "major_topic": false }, { "descriptor": "Genes, Reporter", "descriptor_ui": "D017930", "major_topic": false }, { "descriptor": "HeLa Cells", "descriptor_ui": "D006367", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Luminescent Proteins", "descriptor_ui": "D008164", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Nov 2", "date_precision": "day", "issue": "3", "normalized_date": "2017-11-02", "pages": "626-640.e5", "proceedings_title": null, "publisher": "", "title": "Molecular cell", "volume": "68", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Genetically Encoded Tools for Optical Dissection of the Mammalian Cell Cycle.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The mechanism for sex determination in mammalian germ cells remains unclear. Here, we reconstitute the female sex determination in mouse germ cells in vitro under a defined condition without the use of gonadal somatic cells. We show that retinoic acid (RA) and its key effector, STRA8, are not sufficient to induce the female germ-cell fate. In contrast, bone morphogenetic protein (BMP) and RA synergistically induce primordial germ cells (PGCs)/PGC-like cells (PGCLCs) derived from embryonic stem cells (ESCs) into fetal primary oocytes. The induction is characterized by entry into the meiotic prophase, occurs synchronously and recapitulates cytological and transcriptome progression in vivo faithfully. Importantly, the female germ-cell induction necessitates a proper cellular competence-most typically, DNA demethylation of relevant genes-which is observed in appropriately propagated PGCs/PGCLCs, but not in PGCs/PGCLCs immediately after induction. This provides an explanation for the differential function of BMP signaling between PGC specification and female germ-cell induction. Our findings represent a framework for a comprehensive delineation of the sex-determination pathway in mammalian germ cells, including humans.", "classifications": [ { "id": "Yamamoto", "label": "Group Yamamoto", "parent": "Toyoshima", "type": "group" }, { "id": "Toyoshima", "label": "Team Toyoshima", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Hidetaka", "last_name": "Miyauchi", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Ohta", "name": null }, { "creator_type": "author", "first_name": "So", "last_name": "Nagaoka", "name": null }, { "creator_type": "author", "first_name": "Fumio", "last_name": "Nakaki", "name": null }, { "creator_type": "author", "first_name": "Kotaro", "last_name": "Sasaki", "name": null }, { "creator_type": "author", "first_name": "Katsuhiko", "last_name": "Hayashi", "name": null }, { "creator_type": "author", "first_name": "Yukihiro", "last_name": "Yabuta", "name": null }, { "creator_type": "author", "first_name": "Tomonori", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Mitinori", "last_name": "Saitou", "name": null } ], "identifiers": { "doi": { "normalized": "10.15252/embj.201796875" }, "pmcid": { "normalized": "PMC5666620" }, "pmid": { "normalized": "28928204" } }, "mesh": [ { "descriptor": "Adaptor Proteins, Signal Transducing", "descriptor_ui": "D048868", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Bacterial Proteins", "descriptor_ui": "D001426", "major_topic": false }, { "descriptor": "Bone Morphogenetic Proteins", "descriptor_ui": "D019485", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Fetus", "descriptor_ui": "D005333", "major_topic": false }, { "descriptor": "Gene Expression Profiling", "descriptor_ui": "D020869", "major_topic": false }, { "descriptor": "Gene Expression Regulation, Developmental", "descriptor_ui": "D018507", "major_topic": true }, { "descriptor": "Genes, Reporter", "descriptor_ui": "D017930", "major_topic": false }, { "descriptor": "Luminescent Proteins", "descriptor_ui": "D008164", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred ICR", "descriptor_ui": "D008813", "major_topic": false }, { "descriptor": "Mouse Embryonic Stem Cells", "descriptor_ui": "D000066450", "major_topic": false }, { "descriptor": "Oocytes", "descriptor_ui": "D009865", "major_topic": false }, { "descriptor": "Positive Regulatory Domain I-Binding Factor 1", "descriptor_ui": "D000074462", "major_topic": false }, { "descriptor": "Prophase", "descriptor_ui": "D011418", "major_topic": false }, { "descriptor": "Protein Isoforms", "descriptor_ui": "D020033", "major_topic": false }, { "descriptor": "Sex Determination Processes", "descriptor_ui": "D019849", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Transcription Factors", "descriptor_ui": "D014157", "major_topic": false }, { "descriptor": "Tretinoin", "descriptor_ui": "D014212", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Nov 2", "date_precision": "day", "issue": "21", "normalized_date": "2017-11-02", "pages": "3100-3119", "proceedings_title": null, "publisher": "", "title": "The EMBO journal", "volume": "36", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Bone morphogenetic protein and retinoic acid synergistically specify female germ-cell fate in mice.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "NPM1 mutations define the commonest subgroup of acute myeloid leukemia (AML) and frequently co-occur with FLT3 internal tandem duplications (ITD) or, less commonly, NRAS or KRAS mutations. Co-occurrence of mutant NPM1 with FLT3-ITD carries a significantly worse prognosis than NPM1-RAS combinations. To understand the molecular basis of these observations, we compare the effects of the 2 combinations on hematopoiesis and leukemogenesis in knock-in mice. Early effects of these mutations on hematopoiesis show that compound Npm1(cA/+);Nras(G12D/+) or Npm1(cA);Flt3(ITD) share a number of features: Hox gene overexpression, enhanced self-renewal, expansion of hematopoietic progenitors, and myeloid differentiation bias. However, Npm1(cA);Flt3(ITD) mutants displayed significantly higher peripheral leukocyte counts, early depletion of common lymphoid progenitors, and a monocytic bias in comparison with the granulocytic bias in Npm1(cA/+);Nras(G12D/+) mutants. Underlying this was a striking molecular synergy manifested as a dramatically altered gene expression profile in Npm1(cA);Flt3(ITD) , but not Npm1(cA/+);Nras(G12D/+) , progenitors compared with wild-type. Both double-mutant models developed high-penetrance AML, although latency was significantly longer with Npm1(cA/+);Nras(G12D/+) During AML evolution, both models acquired additional copies of the mutant Flt3 or Nras alleles, but only Npm1(cA/+);Nras(G12D/+) mice showed acquisition of other human AML mutations, including IDH1 R132Q. We also find, using primary Cas9-expressing AMLs, that Hoxa genes and selected interactors or downstream targets are required for survival of both types of double-mutant AML. Our results show that molecular complementarity underlies the higher frequency and significantly worse prognosis associated with NPM1c/FLT3-ITD vs NPM1/NRAS-G12D-mutant AML and functionally confirm the role of HOXA genes in NPM1c-driven AML.", "classifications": [ { "id": "Yusa", "label": "Group Yusa", "parent": "Eiraku", "type": "group" }, { "id": "Eiraku", "label": "Team Eiraku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Oliver M.", "last_name": "Dovey", "name": null }, { "creator_type": "author", "first_name": "Jonathan L.", "last_name": "Cooper", "name": null }, { "creator_type": "author", "first_name": "Annalisa", "last_name": "Mupo", "name": null }, { "creator_type": "author", "first_name": "Carolyn S.", "last_name": "Grove", "name": null }, { "creator_type": "author", "first_name": "Claire", "last_name": "Lynn", "name": null }, { "creator_type": "author", "first_name": "Nathalie", "last_name": "Conte", "name": null }, { "creator_type": "author", "first_name": "Robert M.", "last_name": "Andrews", "name": null }, { "creator_type": "author", "first_name": "Suruchi", "last_name": "Pacharne", "name": null }, { "creator_type": "author", "first_name": "Konstantinos", "last_name": "Tzelepis", "name": null }, { "creator_type": "author", "first_name": "M. S.", "last_name": "Vijayabaskar", "name": null }, { "creator_type": "author", "first_name": "Paul", "last_name": "Green", "name": null }, { "creator_type": "author", "first_name": "Roland", "last_name": "Rad", "name": null }, { "creator_type": "author", "first_name": "Mark", "last_name": "Arends", "name": null }, { "creator_type": "author", "first_name": "Penny", "last_name": "Wright", "name": null }, { "creator_type": "author", "first_name": "Kosuke", "last_name": "Yusa", "name": null }, { "creator_type": "author", "first_name": "Allan", "last_name": "Bradley", "name": null }, { "creator_type": "author", "first_name": "Ignacio", "last_name": "Varela", "name": null }, { "creator_type": "author", "first_name": "George S.", "last_name": "Vassiliou", "name": null } ], "identifiers": { "doi": { "normalized": "10.1182/blood-2017-01-760595" }, "pmcid": { "normalized": "PMC5672315" }, "pmid": { "normalized": "28835438" } }, "mesh": [ { "descriptor": "Alleles", "descriptor_ui": "D000483", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Cell Self Renewal", "descriptor_ui": "D000066673", "major_topic": false }, { "descriptor": "Cell Survival", "descriptor_ui": "D002470", "major_topic": false }, { "descriptor": "Disease Progression", "descriptor_ui": "D018450", "major_topic": false }, { "descriptor": "fms-Like Tyrosine Kinase 3", "descriptor_ui": "D051941", "major_topic": false }, { "descriptor": "Gene Dosage", "descriptor_ui": "D018628", "major_topic": false }, { "descriptor": "Gene Expression Profiling", "descriptor_ui": "D020869", "major_topic": false }, { "descriptor": "Gene Expression Regulation, Leukemic", "descriptor_ui": "D015973", "major_topic": false }, { "descriptor": "Gene Expression Regulation, Neoplastic", "descriptor_ui": "D015972", "major_topic": false }, { "descriptor": "Hematopoietic Stem Cells", "descriptor_ui": "D006412", "major_topic": false }, { "descriptor": "Homeodomain Proteins", "descriptor_ui": "D018398", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Leukemia, Myeloid, Acute", "descriptor_ui": "D015470", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Multipotent Stem Cells", "descriptor_ui": "D039902", "major_topic": false }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": false }, { "descriptor": "Myelopoiesis", "descriptor_ui": "D038042", "major_topic": false }, { "descriptor": "Nuclear Proteins", "descriptor_ui": "D009687", "major_topic": false }, { "descriptor": "Nucleophosmin", "descriptor_ui": "D000090243", "major_topic": false }, { "descriptor": "Penetrance", "descriptor_ui": "D019683", "major_topic": false }, { "descriptor": "Phenotype", "descriptor_ui": "D010641", "major_topic": false }, { "descriptor": "Transcription Factors", "descriptor_ui": "D014157", "major_topic": false }, { "descriptor": "Transcriptome", "descriptor_ui": "D059467", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Oct 26", "date_precision": "day", "issue": "17", "normalized_date": "2017-10-26", "pages": "1911-1922", "proceedings_title": null, "publisher": "", "title": "Blood", "volume": "130", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Molecular synergy underlies the co-occurrence patterns and phenotype of NPM1-mutant acute myeloid leukemia.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor and its expression is influenced by environmental compounds, such as 3-methylcholanthrene (3-MC) and β-naphthoflavone (β-NF). AhR and its downstream genes, such as CYP1A1, are considered to play a pivotal role in xenobiotic responses. AhR signaling has also been proposed to mediate osteogenesis in experimental animals, but its details have remained unclear. Therefore, in this study, we examined the possible roles of AhR in human bone. Immunohistochemical analysis revealed that AhR was detected in both osteoblasts and osteoclasts. We then screened AhR-target genes using a microarray analysis in human osteoblastic hFOB cells. Results of microarray and subsequent PCR analysis did reveal that estrogen metabolizing and synthesizing enzymes, such as CYP1B1 and aromatase, were increased by 3-MC in hFOB and osteosarcoma cell line, MG-63. The subsequent antibody cytokine analysis also demonstrated that interleukin-1β and -6 expression was increased by 3-MC and β-NF in hFOB cells and these interleukins were well known to induce aromatase. We then examined the cell proliferation rate of hFOB and MG-63 cells co-treated with 3-MC and testosterone as an aromatase substrate. The status of cell proliferation in both hFOB and MG-63 cells was stimulated by 3-MC and testosterone treatment, which was also inhibited by an estrogen blocker, aromatase inhibitor, or AhR antagonist. These findings indicated that AhR could regulate estrogen synthesis and metabolism in bone tissues through cytokine/aromatase signaling.", "classifications": [ { "id": "Suzuki", "label": "Group Suzuki", "parent": "Takekawa", "type": "group" }, { "id": "Takekawa", "label": "Team Takekawa", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yasuhiro", "last_name": "Miki", "name": null }, { "creator_type": "author", "first_name": "Shuko", "last_name": "Hata", "name": null }, { "creator_type": "author", "first_name": "Katsuhiko", "last_name": "Ono", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Kiyoshi", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Kumamoto", "name": null }, { "creator_type": "author", "first_name": "Hironobu", "last_name": "Sasano", "name": null } ], "identifiers": { "doi": { "normalized": "10.3390/ijms18102159" }, "pmcid": { "normalized": "PMC5666840" }, "pmid": { "normalized": "29039776" } }, "mesh": [ { "descriptor": "Aromatase", "descriptor_ui": "D001141", "major_topic": false }, { "descriptor": "Bone and Bones", "descriptor_ui": "D001842", "major_topic": false }, { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Cell Proliferation", "descriptor_ui": "D049109", "major_topic": false }, { "descriptor": "Cytokines", "descriptor_ui": "D016207", "major_topic": false }, { "descriptor": "Estrogens", "descriptor_ui": "D004967", "major_topic": false }, { "descriptor": "Gene Expression", "descriptor_ui": "D015870", "major_topic": false }, { "descriptor": "Gene Expression Regulation", "descriptor_ui": "D005786", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Immunohistochemistry", "descriptor_ui": "D007150", "major_topic": false }, { "descriptor": "Methylcholanthrene", "descriptor_ui": "D008748", "major_topic": false }, { "descriptor": "Osteoblasts", "descriptor_ui": "D010006", "major_topic": false }, { "descriptor": "Osteosarcoma", "descriptor_ui": "D012516", "major_topic": false }, { "descriptor": "Receptors, Aryl Hydrocarbon", "descriptor_ui": "D018336", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Oct 17", "date_precision": "day", "issue": "10", "normalized_date": "2017-10-17", "pages": "", "proceedings_title": null, "publisher": "", "title": "International journal of molecular sciences", "volume": "18", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Roles of Aryl Hydrocarbon Receptor in Aromatase-Dependent Cell Proliferation in Human Osteoblasts.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Germline specification underlies human reproduction and evolution, but it has proven difficult to study in humans since it occurs shortly after blastocyst implantation. This process can be modeled with human induced pluripotent stem cells (hiPSCs) by differentiating them into primordial germ cell-like cells (hPGCLCs) through an incipient mesoderm-like cell (iMeLC) state. Here, we elucidate the key transcription factors and their interactions with important signaling pathways in driving hPGCLC differentiation from iPSCs. Germline competence of iMeLCs is dictated by the duration and dosage of WNT signaling, which induces expression of EOMES to activate SOX17, a key driver of hPGCLC specification. Upon hPGCLC induction, BMP signaling activates TFAP2C in a SOX17-independent manner. SOX17 and TFAP2C then cooperatively instate an hPGCLC transcriptional program, including BLIMP1 expression. This specification program diverges from its mouse counterpart regarding key transcription factors and their hierarchies, and it provides a foundation for further study of human germ cell development.", "classifications": [ { "id": "Yamamoto", "label": "Group Yamamoto", "parent": "Toyoshima", "type": "group" }, { "id": "Toyoshima", "label": "Team Toyoshima", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yoji", "last_name": "Kojima", "name": null }, { "creator_type": "author", "first_name": "Kotaro", "last_name": "Sasaki", "name": null }, { "creator_type": "author", "first_name": "Shihori", "last_name": "Yokobayashi", "name": null }, { "creator_type": "author", "first_name": "Yoshitake", "last_name": "Sakai", "name": null }, { "creator_type": "author", "first_name": "Tomonori", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Yukihiro", "last_name": "Yabuta", "name": null }, { "creator_type": "author", "first_name": "Fumio", "last_name": "Nakaki", "name": null }, { "creator_type": "author", "first_name": "So", "last_name": "Nagaoka", "name": null }, { "creator_type": "author", "first_name": "Knut", "last_name": "Woltjen", "name": null }, { "creator_type": "author", "first_name": "Akitsu", "last_name": "Hotta", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Mitinori", "last_name": "Saitou", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.stem.2017.09.005" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "28985527" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Biological Evolution", "descriptor_ui": "D005075", "major_topic": true }, { "descriptor": "Cell Lineage", "descriptor_ui": "D019070", "major_topic": true }, { "descriptor": "Embryo Implantation", "descriptor_ui": "D010064", "major_topic": false }, { "descriptor": "Embryo, Mammalian", "descriptor_ui": "D004622", "major_topic": false }, { "descriptor": "Gene Expression Regulation, Developmental", "descriptor_ui": "D018507", "major_topic": false }, { "descriptor": "Germ Cells", "descriptor_ui": "D005854", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Models, Biological", "descriptor_ui": "D008954", "major_topic": false }, { "descriptor": "Pluripotent Stem Cells", "descriptor_ui": "D039904", "major_topic": false }, { "descriptor": "Primates", "descriptor_ui": "D011323", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Transcription Factors", "descriptor_ui": "D014157", "major_topic": false }, { "descriptor": "Transcription, Genetic", "descriptor_ui": "D014158", "major_topic": true }, { "descriptor": "Transcriptome", "descriptor_ui": "D059467", "major_topic": false }, { "descriptor": "Wnt Signaling Pathway", "descriptor_ui": "D060449", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Oct 5", "date_precision": "day", "issue": "4", "normalized_date": "2017-10-05", "pages": "517-532.e5", "proceedings_title": null, "publisher": "", "title": "Cell stem cell", "volume": "21", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Evolutionarily Distinctive Transcriptional and Signaling Programs Drive Human Germ Cell Lineage Specification from Pluripotent Stem Cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "A new porous coordination polymer (PCP) based on a ligand with a unique bent angle bearing a thiophene-bridged bent carboxylate ligand and the Cu(2+) ion was synthesized and structurally characterized. The structure has a pillared-layer framework based on a kagome-like layer with aromatic partition groups. It exhibits a high CO(2) uptake of 180 mL(STP)/g at 1 bar, and 400 mL(STP)/g at 30 bar at 273 K. The uptakes of C(2)H(2) and C(2)H(4) reach 164 and 160 mL(STP)/g at 298 K and 1 bar, with good selectivity of C(2)H(2) and C(2)H(4) over CH(4), both of which are among the highest levels of reported PCPs.", "classifications": [ { "id": "Hijikata", "label": "Group Hijikata", "parent": "Tsuchiya", "type": "group" }, { "id": "Tsuchiya", "label": "Team Tsuchiya", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Fei", "last_name": "Wang", "name": null }, { "creator_type": "author", "first_name": "Shinpei", "last_name": "Kusaka", "name": null }, { "creator_type": "author", "first_name": "Yuh", "last_name": "Hijikata", "name": null }, { "creator_type": "author", "first_name": "Nobuhiko", "last_name": "Hosono", "name": null }, { "creator_type": "author", "first_name": "Susumu", "last_name": "Kitagawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/acsami.7b01568" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "28426194" } }, "mesh": [], "publication": { "conference_name": null, "date": "2017 Oct 4", "date_precision": "day", "issue": "39", "normalized_date": "2017-10-04", "pages": "33455-33460", "proceedings_title": null, "publisher": "", "title": "ACS applied materials & interfaces", "volume": "9", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Development of a Porous Coordination Polymer with a High Gas Capacity Using a Thiophene-Based Bent Tetracarboxylate Ligand.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "SIGNIFICANCE: For >20 years, physiological signaling associated with the endogenous generation of hydrogen sulfide (H(2)S) has been of significant interest. Despite its presumed importance, the biochemical mechanisms associated with its actions have not been elucidated. Recent Advances: Recently it has been found that H(2)S-related or derived species are highly prevalent in mammalian systems and that these species may be responsible for some, if not the majority, of the biological actions attributed to H(2)S. One of the most prevalent and intriguing species are hydropersulfides (RSSH), which can be present at significant levels. Indeed, it appears that H(2)S and RSSH are intimately linked in biological systems and likely to be mutually inclusive. CRITICAL ISSUES: The fact that H(2)S and polysulfides such as RSSH are present simultaneously means that the biological actions previously assigned to H(2)S can be instead because of the presence of RSSH (or other polysulfides). Thus, it remains possible that hydropersulfides are the biological effectors, and H(2)S serves, to a certain extent, as a marker for persulfides and polysulfides. Addressing this possibility will to a large extent be based on the chemistry of these species. FUTURE DIRECTIONS: Currently, it is known that persulfides possess unique and novel chemical properties that may explain their biological prevalence. However, significantly more work will be required to establish the possible physiological roles of these species. Moreover, an understanding of the regulation of their biosynthesis and degradation will become important topics in piecing together their biology. Antioxid. Redox Signal. 00, 000-000.", "classifications": [ { "id": "Akaike", "label": "Group Akaike", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Lucia", "last_name": "Alvarez", "name": null }, { "creator_type": "author", "first_name": "Christopher L.", "last_name": "Bianco", "name": null }, { "creator_type": "author", "first_name": "John P.", "last_name": "Toscano", "name": null }, { "creator_type": "author", "first_name": "Joseph", "last_name": "Lin", "name": null }, { "creator_type": "author", "first_name": "Takaaki", "last_name": "Akaike", "name": null }, { "creator_type": "author", "first_name": "Jon M.", "last_name": "Fukuto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1089/ars.2017.7081" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "28398141" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cytoprotection", "descriptor_ui": "D019610", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Hydrogen Sulfide", "descriptor_ui": "D006862", "major_topic": false }, { "descriptor": "Oxidation-Reduction", "descriptor_ui": "D010084", "major_topic": true }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Sulfides", "descriptor_ui": "D013440", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Oct 1", "date_precision": "day", "issue": "10", "normalized_date": "2017-10-01", "pages": "622-633", "proceedings_title": null, "publisher": "", "title": "Antioxidants & redox signaling", "volume": "27", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Chemical Biology of Hydropersulfides and Related Species: Possible Roles in Cellular Protection and Redox Signaling.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "We explored the role of the Krebs cycle enzyme fumarate hydratase (FH) in glucose-stimulated insulin secretion (GSIS). Mice lacking Fh1 in pancreatic beta cells (Fh1betaKO mice) appear normal for 6-8 weeks but then develop progressive glucose intolerance and diabetes. Glucose tolerance is rescued by expression of mitochondrial or cytosolic FH but not by deletion of Hif1alpha or Nrf2. Progressive hyperglycemia in Fh1betaKO mice led to dysregulated metabolism in beta cells, a decrease in glucose-induced ATP production, electrical activity, cytoplasmic [Ca(2+)](i) elevation, and GSIS. Fh1 loss resulted in elevated intracellular fumarate, promoting succination of critical cysteines in GAPDH, GMPR, and PARK 7/DJ-1 and cytoplasmic acidification. Intracellular fumarate levels were increased in islets exposed to high glucose and in islets from human donors with type 2 diabetes (T2D). The impaired GSIS in islets from diabetic Fh1betaKO mice was ameliorated after culture under normoglycemic conditions. These studies highlight the role of FH and dysregulated mitochondrial metabolism in T2D.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Julie", "last_name": "Adam", "name": null }, { "creator_type": "author", "first_name": "Reshma", "last_name": "Ramracheya", "name": null }, { "creator_type": "author", "first_name": "Margarita V.", "last_name": "Chibalina", "name": null }, { "creator_type": "author", "first_name": "Nicola", "last_name": "Ternette", "name": null }, { "creator_type": "author", "first_name": "Alexander", "last_name": "Hamilton", "name": null }, { "creator_type": "author", "first_name": "Andrei I.", "last_name": "Tarasov", "name": null }, { "creator_type": "author", "first_name": "Quan", "last_name": "Zhang", "name": null }, { "creator_type": "author", "first_name": "Eduardo", "last_name": "Rebelato", "name": null }, { "creator_type": "author", "first_name": "Nils J. G.", "last_name": "Rorsman", "name": null }, { "creator_type": "author", "first_name": "Rafael", "last_name": "Martin-Del-Rio", "name": null }, { "creator_type": "author", "first_name": "Amy", "last_name": "Lewis", "name": null }, { "creator_type": "author", "first_name": "Gizem", "last_name": "Ozkan", "name": null }, { "creator_type": "author", "first_name": "Hyun Woong", "last_name": "Do", "name": null }, { "creator_type": "author", "first_name": "Peter", "last_name": "Spegel", "name": null }, { "creator_type": "author", "first_name": "Kaori", "last_name": "Saitoh", "name": null }, { "creator_type": "author", "first_name": "Keiko", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Kaori", "last_name": "Igarashi", "name": null }, { "creator_type": "author", "first_name": "Benedikt M.", "last_name": "Kessler", "name": null }, { "creator_type": "author", "first_name": "Christopher W.", "last_name": "Pugh", "name": null }, { "creator_type": "author", "first_name": "Jorge", "last_name": "Tamarit-Rodriguez", "name": null }, { "creator_type": "author", "first_name": "Hindrik", "last_name": "Mulder", "name": null }, { "creator_type": "author", "first_name": "Anne", "last_name": "Clark", "name": null }, { "creator_type": "author", "first_name": "Norma", "last_name": "Frizzell", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Frances M.", "last_name": "Ashcroft", "name": null }, { "creator_type": "author", "first_name": "Andrew", "last_name": "Silver", "name": null }, { "creator_type": "author", "first_name": "Patrick J.", "last_name": "Pollard", "name": null }, { "creator_type": "author", "first_name": "Patrik", "last_name": "Rorsman", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.celrep.2017.08.093" }, "pmcid": { "normalized": "PMC5637167" }, "pmid": { "normalized": "28954230" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Diabetes Mellitus, Type 2", "descriptor_ui": "D003924", "major_topic": false }, { "descriptor": "Fumarate Hydratase", "descriptor_ui": "D005649", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Insulin-Secreting Cells", "descriptor_ui": "D050417", "major_topic": false }, { "descriptor": "Islets of Langerhans", "descriptor_ui": "D007515", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Sep 26", "date_precision": "day", "issue": "13", "normalized_date": "2017-09-26", "pages": "3135-3148", "proceedings_title": null, "publisher": "", "title": "Cell reports", "volume": "20", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Fumarate Hydratase Deletion in Pancreatic beta Cells Leads to Progressive Diabetes.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Electrophiles such as methylmercury (MeHg) affect cellular functions by covalent modification with endogenous thiols. Reactive persulfide species were recently reported to mediate antioxidant responses and redox signaling because of their strong nucleophilicity. In this study, we used MeHg as an environmental electrophile and found that exposure of cells to the exogenous electrophile elevated intracellular concentrations of the endogenous electrophilic molecule 8-nitroguanosine 3',5'-cyclic monophosphate (8-nitro-cGMP), accompanied by depletion of reactive persulfide species and 8-SH-cGMP which is a metabolite of 8-nitro-cGMP. Exposure to MeHg also induced S-guanylation and activation of H-Ras followed by injury to cerebellar granule neurons. The electrophile-induced activation of redox signaling and the consequent cell damage were attenuated by pretreatment with a reactive persulfide species donor. In conclusion, exogenous electrophiles such as MeHg with strong electrophilicity impair the redox signaling regulatory mechanism, particularly of intracellular reactive persulfide species and therefore lead to cellular pathogenesis. Our results suggest that reactive persulfide species may be potential therapeutic targets for attenuating cell injury by electrophiles.", "classifications": [ { "id": "Akaike", "label": "Group Akaike", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Group Nishida", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Hideshi", "last_name": "Ihara", "name": null }, { "creator_type": "author", "first_name": "Shingo", "last_name": "Kasamatsu", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Kitamura", "name": null }, { "creator_type": "author", "first_name": "Akira", "last_name": "Nishimura", "name": null }, { "creator_type": "author", "first_name": "Hiroyasu", "last_name": "Tsutsuki", "name": null }, { "creator_type": "author", "first_name": "Tomoaki", "last_name": "Ida", "name": null }, { "creator_type": "author", "first_name": "Kento", "last_name": "Ishizaki", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Toyama", "name": null }, { "creator_type": "author", "first_name": "Eiko", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Hisyam", "last_name": "Abdul Hamid", "name": null }, { "creator_type": "author", "first_name": "Minkyung", "last_name": "Jung", "name": null }, { "creator_type": "author", "first_name": "Tetsuro", "last_name": "Matsunaga", "name": null }, { "creator_type": "author", "first_name": "Shigemoto", "last_name": "Fujii", "name": null }, { "creator_type": "author", "first_name": "Tomohiro", "last_name": "Sawa", "name": null }, { "creator_type": "author", "first_name": "Motohiro", "last_name": "Nishida", "name": null }, { "creator_type": "author", "first_name": "Yoshito", "last_name": "Kumagai", "name": null }, { "creator_type": "author", "first_name": "Takaaki", "last_name": "Akaike", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/acs.chemrestox.7b00120" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "28837763" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Antibodies", "descriptor_ui": "D000906", "major_topic": false }, { "descriptor": "Cell Survival", "descriptor_ui": "D002470", "major_topic": false }, { "descriptor": "Chromatography, High Pressure Liquid", "descriptor_ui": "D002851", "major_topic": false }, { "descriptor": "Cyclic GMP", "descriptor_ui": "D006152", "major_topic": false }, { "descriptor": "Extracellular Signal-Regulated MAP Kinases", "descriptor_ui": "D048049", "major_topic": false }, { "descriptor": "Immunohistochemistry", "descriptor_ui": "D007150", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Methylmercury Compounds", "descriptor_ui": "D008767", "major_topic": false }, { "descriptor": "Microscopy, Fluorescence", "descriptor_ui": "D008856", "major_topic": false }, { "descriptor": "Naphthoquinones", "descriptor_ui": "D009285", "major_topic": false }, { "descriptor": "Nitric Oxide", "descriptor_ui": "D009569", "major_topic": false }, { "descriptor": "Oxidation-Reduction", "descriptor_ui": "D010084", "major_topic": false }, { "descriptor": "PC12 Cells", "descriptor_ui": "D016716", "major_topic": false }, { "descriptor": "ras Proteins", "descriptor_ui": "D018631", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Rats, Wistar", "descriptor_ui": "D017208", "major_topic": false }, { "descriptor": "Reactive Oxygen Species", "descriptor_ui": "D017382", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Spectrometry, Mass, Electrospray Ionization", "descriptor_ui": "D021241", "major_topic": false }, { "descriptor": "Sulfides", "descriptor_ui": "D013440", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Sep 18", "date_precision": "day", "issue": "9", "normalized_date": "2017-09-18", "pages": "1673-1684", "proceedings_title": null, "publisher": "", "title": "Chemical research in toxicology", "volume": "30", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Exposure to Electrophiles Impairs Reactive Persulfide-Dependent Redox Signaling in Neuronal Cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Spinocerebellar ataxia type 36 is a late-onset, slowly progressive cerebellar syndrome with motor neuron degeneration that is caused by expansions of a hexanucleotide repeat (GGCCTG) in the noncoding region of NOP56 gene, with a histopathological feature of RNA foci formation in postmortem tissues. Here, we report a cellular model using the spinocerebellar ataxia type 36 patient induced pluripotent stem cells (iPSCs). We generated iPSCs from spinocerebellar ataxia type 36 patients and differentiated them into neurons. The number of RNA-foci-positive cells was increased in patient iPSCs and iPSC-derived neurons. Treatment of the 2'-O, 4'-C-ethylene-bridged nucleic acid antisense oligonucleotides (ASOs) targeting NOP56 pre-mRNA reduced RNA-foci-positive cells to approximately 50% in patient iPSCs and iPSC-derived neurons. NOP56 mRNA expression levels were lower in patient iPSCs and iPSC-derived neurons than in healthy control neurons. One of the ASOs reduced the number of RNA-foci-positive cells without altering NOP56 mRNA expression levels in patient iPSCs and iPSC-derived neurons. These data show that iPSCs from spinocerebellar ataxia type 36 patients can be useful for evaluating the effects of ASOs toward GGCCTG repeat expansion in spinocerebellar ataxia type 36.", "classifications": [ { "id": "Yamamoto", "label": "Group Yamamoto", "parent": "Toyoshima", "type": "group" }, { "id": "Toyoshima", "label": "Team Toyoshima", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Kosuke", "last_name": "Matsuzono", "name": null }, { "creator_type": "author", "first_name": "Keiko", "last_name": "Imamura", "name": null }, { "creator_type": "author", "first_name": "Nagahisa", "last_name": "Murakami", "name": null }, { "creator_type": "author", "first_name": "Kayoko", "last_name": "Tsukita", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Yuishin", "last_name": "Izumi", "name": null }, { "creator_type": "author", "first_name": "Ryuji", "last_name": "Kaji", "name": null }, { "creator_type": "author", "first_name": "Yasuyuki", "last_name": "Ohta", "name": null }, { "creator_type": "author", "first_name": "Toru", "last_name": "Yamashita", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Abe", "name": null }, { "creator_type": "author", "first_name": "Haruhisa", "last_name": "Inoue", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.omtn.2017.06.017" }, "pmcid": { "normalized": "PMC5504081" }, "pmid": { "normalized": "28918022" } }, "mesh": [], "publication": { "conference_name": null, "date": "2017 Sep 15", "date_precision": "day", "issue": "", "normalized_date": "2017-09-15", "pages": "211-219", "proceedings_title": null, "publisher": "", "title": "Molecular therapy. Nucleic acids", "volume": "8", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Antisense Oligonucleotides Reduce RNA Foci in Spinocerebellar Ataxia 36 Patient iPSCs.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The TBX2 subfamily (TBXs 2, 3, 4 and 5) transactivates or represses genes involved in lung organogenesis. Yet TBX2 subfamily expression in pathogenesis of non-small cell lung cancer (NSCLC), the most common lung malignancy, remains elusive. We sought to probe the expression profile of the TBX2 subfamily in early phases of NSCLC. Expression of TBX2 subfamily was analyzed in datasets of pan-normal specimens as well as NSCLCs and normal lung tissues. TBX2 subfamily expression in matched normal lungs, premalignant hyperplasias and NSCLCs was profiled by transcriptome sequencing. TBX2 subfamily expression was evaluated in the cancerization field consisting of matched NSCLCs and adjacent cytologically-normal airways relative to distant normal lungs and in a dataset of normal bronchial samples from smokers with indeterminate nodules suspicious for malignancy. Statistical analysis was performed using R. TBX2 subfamily expression was markedly elevated in normal lungs relative to other organ-specific normal tissues. Expression of the TBXs was significantly suppressed in NSCLCs relative to normal lungs (P < 10(-9)). TBX2 subfamily was significantly progressively decreased across premalignant lesions and NSCLCs relative to normal lungs (P < 10(-4)). The subfamily was significantly suppressed in NSCLCs and adjacent normal-appearing airways relative to distant normal lung tissues (P < 10(-15)). Further, suppressed TBX2 subfamily expression in normal bronchi was associated with lung cancer status (P < 10(-5)) in smokers. Our findings suggest that the TBX2 subfamily is notably suppressed in human NSCLC pathogenesis and may serve as a high-potential biomarker for early lung cancer detection in high-risk smokers.", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Athar A.", "last_name": "Khalil", "name": null }, { "creator_type": "author", "first_name": "Smruthy", "last_name": "Sivakumar", "name": null }, { "creator_type": "author", "first_name": "Frances Anthony San", "last_name": "Lucas", "name": null }, { "creator_type": "author", "first_name": "Tina", "last_name": "McDowell", "name": null }, { "creator_type": "author", "first_name": "Wenhua", "last_name": "Lang", "name": null }, { "creator_type": "author", "first_name": "Kazuhiro", "last_name": "Tabata", "name": null }, { "creator_type": "author", "first_name": "Junya", "last_name": "Fujimoto", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null }, { "creator_type": "author", "first_name": "Avrum", "last_name": "Spira", "name": null }, { "creator_type": "author", "first_name": "Paul", "last_name": "Scheet", "name": null }, { "creator_type": "author", "first_name": "Georges", "last_name": "Nemer", "name": null }, { "creator_type": "author", "first_name": "Humam", "last_name": "Kadara", "name": null } ], "identifiers": { "doi": { "normalized": "10.18632/oncotarget.19938" }, "pmcid": { "normalized": "PMC5620251" }, "pmid": { "normalized": "28978111" } }, "mesh": [], "publication": { "conference_name": null, "date": "2017 Sep 15", "date_precision": "day", "issue": "40", "normalized_date": "2017-09-15", "pages": "68230-68241", "proceedings_title": null, "publisher": "", "title": "Oncotarget", "volume": "8", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "TBX2 subfamily suppression in lung cancer pathogenesis: a high-potential marker for early detection.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The kidney expresses protease-activated receptor-1 (PAR-1). PAR-1 is known as a thrombin receptor, but its role in kidney injury is not well understood. In this study, we examined the contribution of PAR-1 to kidney glomerular injury and the effects of its inhibition on development of nephropathy. Mice were divided into 3 groups: control, doxorubicin + vehicle (15 mg/kg doxorubicin and saline) and doxorubicin + Q94 (doxorubicin at 15 mg/kg and the PAR-1 antagonist Q94 at 5 mg/kg/d) groups. Where indicated, doxorubicin was administered intravenously and PAR-1 antagonist or saline vehicle by subcutaneous osmotic mini-pump. PAR-1 expression was increased in glomeruli of mice treated with doxorubicin. Q94 treatment significantly suppressed the increased albuminuria in these nephropathic mice. Pathological analysis showed that Q94 treatment significantly attenuated periodic acid-Schiff and desmin staining, indicators of podocyte injury, and also decreased glomerular levels of podocin and nephrin. Furthermore, thrombin increased intracellular calcium levels in podocytes. This increase was suppressed by Q94 and Rox4560, a transient receptor potential cation channel (TRPC)3/6 antagonist. In addition, both Q94 and Rox4560 suppressed the doxorubicin-induced increase in activities of caspase-9 and caspase-3 in podocytes. These data suggested that PAR-1 contributes to development of podocyte and glomerular injury and that PAR-1 antagonists have therapeutic potential.", "classifications": [ { "id": "Nishida", "label": "Group Nishida", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yu", "last_name": "Guan", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Nakano", "name": null }, { "creator_type": "author", "first_name": "Yifan", "last_name": "Zhang", "name": null }, { "creator_type": "author", "first_name": "Lei", "last_name": "Li", "name": null }, { "creator_type": "author", "first_name": "Wenhua", "last_name": "Liu", "name": null }, { "creator_type": "author", "first_name": "Motohiro", "last_name": "Nishida", "name": null }, { "creator_type": "author", "first_name": "Takashige", "last_name": "Kuwabara", "name": null }, { "creator_type": "author", "first_name": "Asahiro", "last_name": "Morishita", "name": null }, { "creator_type": "author", "first_name": "Hirofumi", "last_name": "Hitomi", "name": null }, { "creator_type": "author", "first_name": "Kiyoshi", "last_name": "Mori", "name": null }, { "creator_type": "author", "first_name": "Masashi", "last_name": "Mukoyama", "name": null }, { "creator_type": "author", "first_name": "Tsutomu", "last_name": "Masaki", "name": null }, { "creator_type": "author", "first_name": "Katsuya", "last_name": "Hirano", "name": null }, { "creator_type": "author", "first_name": "Akira", "last_name": "Nishiyama", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.jphs.2017.09.002" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "29110957" } }, "mesh": [], "publication": { "conference_name": null, "date": "2017 Sep 14", "date_precision": "day", "issue": "", "normalized_date": "2017-09-14", "pages": "S1347-8613(17)30128-7", "proceedings_title": null, "publisher": "", "title": "Journal of pharmacological sciences", "volume": "", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "A protease-activated receptor-1 antagonist protects against podocyte injury in a mouse model of nephropathy.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Cancer cells alter their metabolism for the production of precursors of macromolecules. However, the control mechanisms underlying this reprogramming are poorly understood. Here we show that metabolic reprogramming of colorectal cancer is caused chiefly by aberrant MYC expression. Multiomics-based analyses of paired normal and tumor tissues from 275 patients with colorectal cancer revealed that metabolic alterations occur at the adenoma stage of carcinogenesis, in a manner not associated with specific gene mutations involved in colorectal carcinogenesis. MYC expression induced at least 215 metabolic reactions by changing the expression levels of 121 metabolic genes and 39 transporter genes. Further, MYC negatively regulated the expression of genes involved in mitochondrial biogenesis and maintenance but positively regulated genes involved in DNA and histone methylation. Knockdown of MYC in colorectal cancer cells reset the altered metabolism and suppressed cell growth. Moreover, inhibition of MYC target pyrimidine synthesis genes such as CAD, UMPS, and CTPS blocked cell growth, and thus are potential targets for colorectal cancer therapy.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Kiyotoshi", "last_name": "Satoh", "name": null }, { "creator_type": "author", "first_name": "Shinichi", "last_name": "Yachida", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Sugimoto", "name": null }, { "creator_type": "author", "first_name": "Minoru", "last_name": "Oshima", "name": null }, { "creator_type": "author", "first_name": "Toshitaka", "last_name": "Nakagawa", "name": null }, { "creator_type": "author", "first_name": "Shintaro", "last_name": "Akamoto", "name": null }, { "creator_type": "author", "first_name": "Sho", "last_name": "Tabata", "name": null }, { "creator_type": "author", "first_name": "Kaori", "last_name": "Saitoh", "name": null }, { "creator_type": "author", "first_name": "Keiko", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Saya", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Kaori", "last_name": "Igarashi", "name": null }, { "creator_type": "author", "first_name": "Yumi", "last_name": "Aizawa", "name": null }, { "creator_type": "author", "first_name": "Rie", "last_name": "Kajino-Sakamoto", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Kojima", "name": null }, { "creator_type": "author", "first_name": "Teruaki", "last_name": "Fujishita", "name": null }, { "creator_type": "author", "first_name": "Ayame", "last_name": "Enomoto", "name": null }, { "creator_type": "author", "first_name": "Akiyoshi", "last_name": "Hirayama", "name": null }, { "creator_type": "author", "first_name": "Takamasa", "last_name": "Ishikawa", "name": null }, { "creator_type": "author", "first_name": "Makoto Mark", "last_name": "Taketo", "name": null }, { "creator_type": "author", "first_name": "Yoshio", "last_name": "Kushida", "name": null }, { "creator_type": "author", "first_name": "Reiji", "last_name": "Haba", "name": null }, { "creator_type": "author", "first_name": "Keiichi", "last_name": "Okano", "name": null }, { "creator_type": "author", "first_name": "Masaru", "last_name": "Tomita", "name": null }, { "creator_type": "author", "first_name": "Yasuyuki", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Shinji", "last_name": "Fukuda", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Aoki", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null } ], "identifiers": { "doi": { "normalized": "10.1073/pnas.1710366114" }, "pmcid": { "normalized": "PMC5604037" }, "pmid": { "normalized": "28847964" } }, "mesh": [ { "descriptor": "Adenoma", "descriptor_ui": "D000236", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Carcinogenesis", "descriptor_ui": "D063646", "major_topic": false }, { "descriptor": "Cell Proliferation", "descriptor_ui": "D049109", "major_topic": false }, { "descriptor": "Colorectal Neoplasms", "descriptor_ui": "D015179", "major_topic": false }, { "descriptor": "Disease Models, Animal", "descriptor_ui": "D004195", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Genes, myc", "descriptor_ui": "D016259", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Metabolomics", "descriptor_ui": "D055432", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Proto-Oncogene Proteins c-myc", "descriptor_ui": "D016271", "major_topic": false }, { "descriptor": "Pyrimidines", "descriptor_ui": "D011743", "major_topic": false }, { "descriptor": "Transcriptome", "descriptor_ui": "D059467", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Sep 12", "date_precision": "day", "issue": "37", "normalized_date": "2017-09-12", "pages": "E7697-E7706", "proceedings_title": null, "publisher": "", "title": "Proceedings of the National Academy of Sciences of the United States of America", "volume": "114", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Global metabolic reprogramming of colorectal cancer occurs at adenoma stage and is induced by MYC.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The skin surface area varies flexibly in response to body shape changes. Skin homeostasis is maintained by stem cells residing in the basal layer of the interfollicular epidermis. However, how the interfollicular epidermal stem cells response to physiological body shape changes remains elusive. Here, we identify a highly proliferative interfollicular epidermal basal cell population in the rapidly expanding abdominal skin of pregnant mice. These cells express Tbx3 that is necessary for their propagation to drive skin expansion. The Tbx3(+) basal cells are generated from Axin2(+) interfollicular epidermal stem cells through planar-oriented asymmetric or symmetric cell divisions, and express transit-amplifying cell marker CD71. This biased division of Axin2(+) interfollicular epidermal stem cells is induced by Sfrp1 and Igfbp2 proteins secreted from dermal cells. The Tbx3(+) basal cells promote wound repair, which is enhanced by Sfrp1 and Igfbp2. This study elucidates the interfollicular epidermal stem cell/progeny organisation during pregnancy and suggests its application in regenerative medicine.The abdominal skin expands rapidly during pregnancy. Here the authors show that a population of highly proliferative stem cell progenies expressing the transcription factor Tbx3 is required for abdominal skin expansion in pregnant mice.", "classifications": [ { "id": "Toyoshima", "label": "Group Toyoshima", "parent": "Toyoshima", "type": "group" }, { "id": "Toyoshima", "label": "Team Toyoshima", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Ryo", "last_name": "Ichijo", "name": null }, { "creator_type": "author", "first_name": "Hiroki", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Saori", "last_name": "Yoneda", "name": null }, { "creator_type": "author", "first_name": "Yui", "last_name": "Iizuka", "name": null }, { "creator_type": "author", "first_name": "Hirokazu", "last_name": "Kubo", "name": null }, { "creator_type": "author", "first_name": "Shigeru", "last_name": "Matsumura", "name": null }, { "creator_type": "author", "first_name": "Satsuki", "last_name": "Kitano", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Miyachi", "name": null }, { "creator_type": "author", "first_name": "Tetsuya", "last_name": "Honda", "name": null }, { "creator_type": "author", "first_name": "Fumiko", "last_name": "Toyoshima", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41467-017-00433-7" }, "pmcid": { "normalized": "PMC5593911" }, "pmid": { "normalized": "28894084" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Axin Protein", "descriptor_ui": "D060466", "major_topic": false }, { "descriptor": "Cell Proliferation", "descriptor_ui": "D049109", "major_topic": false }, { "descriptor": "Dermis", "descriptor_ui": "D020405", "major_topic": false }, { "descriptor": "Epithelial Cells", "descriptor_ui": "D004847", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Intercellular Signaling Peptides and Proteins", "descriptor_ui": "D036341", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Membrane Proteins", "descriptor_ui": "D008565", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Pregnancy", "descriptor_ui": "D011247", "major_topic": false }, { "descriptor": "Regeneration", "descriptor_ui": "D012038", "major_topic": false }, { "descriptor": "Secreted Frizzled-Related Proteins", "descriptor_ui": "D000094742", "major_topic": false }, { "descriptor": "Skin", "descriptor_ui": "D012867", "major_topic": false }, { "descriptor": "Stem Cells", "descriptor_ui": "D013234", "major_topic": false }, { "descriptor": "T-Box Domain Proteins", "descriptor_ui": "D020825", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Sep 11", "date_precision": "day", "issue": "1", "normalized_date": "2017-09-11", "pages": "508", "proceedings_title": null, "publisher": "", "title": "Nature communications", "volume": "8", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Tbx3-dependent amplifying stem cell progeny drives interfollicular epidermal expansion during pregnancy and regeneration.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Charcot-Marie-Tooth disease (CMT) is the most common inherited neuropathy. The majority of CMT is demyelinating type (demyelinating CMT) caused by Schwann cell involvement. Although a large number of genes responsible for demyelinating CMT have been found, the common molecular target of the pathophysiology caused by these different genes in demyelinating CMT is still unknown. We generated induced pluripotent stem cells (iPSCs) from healthy controls and patients with demyelinating CMT caused by duplication in peripheral myelin protein 22 kDa (PMP22) or point mutations in myelin protein zero (MPZ) or early growth response 2 (EGR2). iPSCs were differentiated into neural crest cells, progenitors of Schwann cells, followed by purification using the neural crest cell markers p75 and human natural killer-1. To identify a disease-relevant molecular signature at the early stage of demyelinating CMT, we conducted global gene expression analysis of iPSC-derived neural crest cells and found that a glutathione-mediated detoxification pathway was one of the related pathways in demyelinating CMT. mRNA expression of glutathione S-transferase theta 2 (GSTT2), encoding an important enzyme for glutathione-mediated detoxification, and production of reactive oxygen species were increased in demyelinating CMT. Our study suggested that patient-iPSC-derived neural crest cells could be a cellular model for investigating genetically heterogeneous disease CMT and might provide a therapeutic target for the disease.", "classifications": [ { "id": "Yamamoto", "label": "Group Yamamoto", "parent": "Toyoshima", "type": "group" }, { "id": "Toyoshima", "label": "Team Toyoshima", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Fukiko", "last_name": "Kitani-Morii", "name": null }, { "creator_type": "author", "first_name": "Keiko", "last_name": "Imamura", "name": null }, { "creator_type": "author", "first_name": "Takayuki", "last_name": "Kondo", "name": null }, { "creator_type": "author", "first_name": "Ryo", "last_name": "Ohara", "name": null }, { "creator_type": "author", "first_name": "Takako", "last_name": "Enami", "name": null }, { "creator_type": "author", "first_name": "Ran", "last_name": "Shibukawa", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Kazuya", "last_name": "Sekiguchi", "name": null }, { "creator_type": "author", "first_name": "Junya", "last_name": "Toguchida", "name": null }, { "creator_type": "author", "first_name": "Toshiki", "last_name": "Mizuno", "name": null }, { "creator_type": "author", "first_name": "Masanori", "last_name": "Nakagawa", "name": null }, { "creator_type": "author", "first_name": "Haruhisa", "last_name": "Inoue", "name": null } ], "identifiers": { "doi": { "normalized": "10.1097/wnr.0000000000000831" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "28704293" } }, "mesh": [ { "descriptor": "Charcot-Marie-Tooth Disease", "descriptor_ui": "D002607", "major_topic": false }, { "descriptor": "Early Growth Response Protein 2", "descriptor_ui": "D051767", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Gene Expression", "descriptor_ui": "D015870", "major_topic": false }, { "descriptor": "Glutathione Transferase", "descriptor_ui": "D005982", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Induced Pluripotent Stem Cells", "descriptor_ui": "D057026", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Myelin P0 Protein", "descriptor_ui": "D018993", "major_topic": false }, { "descriptor": "Myelin Proteins", "descriptor_ui": "D009185", "major_topic": false }, { "descriptor": "Neural Crest", "descriptor_ui": "D009432", "major_topic": false }, { "descriptor": "Reactive Oxygen Species", "descriptor_ui": "D017382", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Sep 6", "date_precision": "day", "issue": "13", "normalized_date": "2017-09-06", "pages": "814-821", "proceedings_title": null, "publisher": "", "title": "Neuroreport", "volume": "28", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Analysis of neural crest cells from Charcot-Marie-Tooth disease patients demonstrates disease-relevant molecular signature.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Mitogen-activated protein kinase (MAPK) pathways that direct cellular responses are involved in various biological processes; the RAS-RAF-MEK-ERK pathway is one of the most important MAPK pathways. It is frequently activated in human malignant tumors such as melanomas, thyroid tumors and colorectal carcinomas. Therefore, targeting this pathway has been considered an attractive strategy for new anticancer drugs. In particular, MEK is a promising target because it is a kinase that directly phosphorylates ERK. We performed a screening to discover new MEK inhibitors, and found a guanine derivative produced by Streptomyces sp. MK63-43F2. This guanine derivative was identified to be 2-amino-4-methoxy-5-cyanopyrrolo[2,3-d]pyrimidine (1) through spectroscopic analysis. Compound 1 inhibited MEK1 kinase activity in an ATP-dependent manner and suppressed the phosphorylation of ERK in cancer cells and cell proliferation. Therefore, 1 might be a potent lead compound for new MEK inhibitors.The Journal of Antibiotics advance online publication, 6 September 2017; doi:10.1038/ja.2017.100.", "classifications": [ { "id": "Takekawa", "label": "Group Takekawa", "parent": "Takekawa", "type": "group" }, { "id": "Takekawa", "label": "Team Takekawa", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Masatomi", "last_name": "Iijima", "name": null }, { "creator_type": "author", "first_name": "Yuji", "last_name": "Kubota", "name": null }, { "creator_type": "author", "first_name": "Ryuichi", "last_name": "Sawa", "name": null }, { "creator_type": "author", "first_name": "Yumiko", "last_name": "Kubota", "name": null }, { "creator_type": "author", "first_name": "Masaki", "last_name": "Hatano", "name": null }, { "creator_type": "author", "first_name": "Masayuki", "last_name": "Igarashi", "name": null }, { "creator_type": "author", "first_name": "Manabu", "last_name": "Kawada", "name": null }, { "creator_type": "author", "first_name": "Isao", "last_name": "Momose", "name": null }, { "creator_type": "author", "first_name": "Mutsuhiro", "last_name": "Takekawa", "name": null }, { "creator_type": "author", "first_name": "Masakatsu", "last_name": "Shibasaki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/ja.2017.100" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "28874847" } }, "mesh": [], "publication": { "conference_name": null, "date": "2017 Sep 6", "date_precision": "day", "issue": "", "normalized_date": "2017-09-06", "pages": "", "proceedings_title": null, "publisher": "", "title": "The Journal of antibiotics", "volume": "", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "A guanine derivative as a new MEK inhibitor produced by Streptomyces sp. MK63-43F2.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Numerous otherwise difficult applications have been realized with materials, the chemical/physical properties of which can be controlled by external stimuli such as heat, pressure, photo-irradiation, and voltage bias. However, the complexity of design and the lack of easy-to-conduct synthetic methods make the creation of on-demand stimuli responsive materials a formidable task. Here we report an electric-stimuli-responsive multifunctional material, [10]CPP-I: crystalline assembly of a hydrocarbon nanoring ([10]cycloparaphenylene: [10]CPP) as an \"electro-responsive porous host\" and iodine as a \"potentially functional molecule\". Through applying electric stimulus, [10]CPP-I turned to exhibit two attractive properties: electronic conductivity and white light emission. We revealed that electric stimuli trigger the cascade formation of polyiodide chains inside the [10]CPP assembly through charge transfer, leading to the emergence of these properties. This \"responsive porous host\" approach is expected to be applicable for different stimuli, and opens the path for devising a generic strategy to the development of stimuli-responsive materials.", "classifications": [ { "id": "Hijikata", "label": "Group Hijikata", "parent": "Tsuchiya", "type": "group" }, { "id": "Tsuchiya", "label": "Team Tsuchiya", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Noriaki", "last_name": "Ozaki", "name": null }, { "creator_type": "author", "first_name": "Hirotoshi", "last_name": "Sakamoto", "name": null }, { "creator_type": "author", "first_name": "Taishi", "last_name": "Nishihara", "name": null }, { "creator_type": "author", "first_name": "Toshihiko", "last_name": "Fujimori", "name": null }, { "creator_type": "author", "first_name": "Yuh", "last_name": "Hijikata", "name": null }, { "creator_type": "author", "first_name": "Ryuto", "last_name": "Kimura", "name": null }, { "creator_type": "author", "first_name": "Stephan", "last_name": "Irle", "name": null }, { "creator_type": "author", "first_name": "Kenichiro", "last_name": "Itami", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/anie.201703648" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "28585773" } }, "mesh": [], "publication": { "conference_name": null, "date": "2017 Sep 4", "date_precision": "day", "issue": "37", "normalized_date": "2017-09-04", "pages": "11196-11202", "proceedings_title": null, "publisher": "", "title": "Angewandte Chemie (International ed. in English)", "volume": "56", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Electrically Activated Conductivity and White Light Emission of a Hydrocarbon Nanoring-Iodine Assembly.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "In the FANTOM5 project, transcription initiation events across the human and mouse genomes were mapped at a single base-pair resolution and their frequencies were monitored by CAGE (Cap Analysis of Gene Expression) coupled with single-molecule sequencing. Approximately three thousands of samples, consisting of a variety of primary cells, tissues, cell lines, and time series samples during cell activation and development, were subjected to a uniform pipeline of CAGE data production. The analysis pipeline started by measuring RNA extracts to assess their quality, and continued to CAGE library production by using a robotic or a manual workflow, single molecule sequencing, and computational processing to generate frequencies of transcription initiation. Resulting data represents the consequence of transcriptional regulation in each analyzed state of mammalian cells. Non-overlapping peaks over the CAGE profiles, approximately 200,000 and 150,000 peaks for the human and mouse genomes, were identified and annotated to provide precise location of known promoters as well as novel ones, and to quantify their activities.", "classifications": [ { "id": "Enomoto", "label": "Group Enomoto", "parent": "Enomoto", "type": "group" }, { "id": "Enomoto", "label": "Team Enomoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Shuhei", "last_name": "Noguchi", "name": null }, { "creator_type": "author", "first_name": "Takahiro", "last_name": "Arakawa", "name": null }, { "creator_type": "author", "first_name": "Shiro", "last_name": "Fukuda", "name": null }, { "creator_type": "author", "first_name": "Masaaki", "last_name": "Furuno", "name": null }, { "creator_type": "author", "first_name": "Akira", "last_name": "Hasegawa", "name": null }, { "creator_type": "author", "first_name": "Fumi", "last_name": "Hori", "name": null }, { "creator_type": "author", "first_name": "Sachi", "last_name": "Ishikawa-Kato", "name": null }, { "creator_type": "author", "first_name": "Kaoru", "last_name": "Kaida", "name": null }, { "creator_type": "author", "first_name": "Ai", "last_name": "Kaiho", "name": null }, { "creator_type": "author", "first_name": "Mutsumi", "last_name": "Kanamori-Katayama", "name": null }, { "creator_type": "author", "first_name": "Tsugumi", "last_name": "Kawashima", "name": null }, { "creator_type": "author", "first_name": "Miki", "last_name": "Kojima", "name": null }, { "creator_type": "author", "first_name": "Atsutaka", "last_name": "Kubosaki", "name": null }, { "creator_type": "author", "first_name": "Ri-Ichiroh", "last_name": "Manabe", "name": null }, { "creator_type": "author", "first_name": "Mitsuyoshi", "last_name": "Murata", "name": null }, { "creator_type": "author", "first_name": "Sayaka", "last_name": "Nagao-Sato", "name": null }, { "creator_type": "author", "first_name": "Kenichi", "last_name": "Nakazato", "name": null }, { "creator_type": "author", "first_name": "Noriko", "last_name": "Ninomiya", "name": null }, { "creator_type": "author", "first_name": "Hiromi", "last_name": "Nishiyori-Sueki", "name": null }, { "creator_type": "author", "first_name": "Shohei", "last_name": "Noma", "name": null }, { "creator_type": "author", "first_name": "Eri", "last_name": "Saijyo", "name": null }, { "creator_type": "author", "first_name": "Akiko", "last_name": "Saka", "name": null }, { "creator_type": "author", "first_name": "Mizuho", "last_name": "Sakai", "name": null }, { "creator_type": "author", "first_name": "Christophe", "last_name": "Simon", "name": null }, { "creator_type": "author", "first_name": "Naoko", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Michihira", "last_name": "Tagami", "name": null }, { "creator_type": "author", "first_name": "Shoko", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Shigehiro", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Peter", "last_name": "Arner", "name": null }, { "creator_type": "author", "first_name": "Richard A.", "last_name": "Axton", "name": null }, { "creator_type": "author", "first_name": "Magda", "last_name": "Babina", "name": null }, { "creator_type": "author", "first_name": "J. 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"last_name": "Wolvetang", "name": null }, { "creator_type": "author", "first_name": "Yoko", "last_name": "Yamaguchi", "name": null }, { "creator_type": "author", "first_name": "Masayuki", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Chiyo", "last_name": "Yanagi-Mizuochi", "name": null }, { "creator_type": "author", "first_name": "Misako", "last_name": "Yoneda", "name": null }, { "creator_type": "author", "first_name": "Yohei", "last_name": "Yonekura", "name": null }, { "creator_type": "author", "first_name": "Peter G.", "last_name": "Zhang", "name": null }, { "creator_type": "author", "first_name": "Silvia", "last_name": "Zucchelli", "name": null }, { "creator_type": "author", "first_name": "Imad", "last_name": "Abugessaisa", "name": null }, { "creator_type": "author", "first_name": "Erik", "last_name": "Arner", "name": null }, { "creator_type": "author", "first_name": "Jayson", "last_name": "Harshbarger", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Kondo", "name": null }, { "creator_type": "author", "first_name": "Timo", "last_name": "Lassmann", "name": null }, { "creator_type": "author", "first_name": "Marina", "last_name": "Lizio", "name": null }, { "creator_type": "author", "first_name": "Serkan", "last_name": "Sahin", "name": null }, { "creator_type": "author", "first_name": "Thierry", "last_name": "Sengstag", "name": null }, { "creator_type": "author", "first_name": "Jessica", "last_name": "Severin", "name": null }, { "creator_type": "author", "first_name": "Hisashi", "last_name": "Shimoji", "name": null }, { "creator_type": "author", "first_name": "Masanori", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Harukazu", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Jun", "last_name": "Kawai", "name": null }, { "creator_type": "author", "first_name": "Naoto", "last_name": "Kondo", "name": null }, { "creator_type": "author", "first_name": "Masayoshi", "last_name": "Itoh", "name": null }, { "creator_type": "author", "first_name": "Carsten O.", "last_name": "Daub", "name": null }, { "creator_type": "author", "first_name": "Takeya", "last_name": "Kasukawa", "name": null }, { "creator_type": "author", "first_name": "Hideya", "last_name": "Kawaji", "name": null }, { "creator_type": "author", "first_name": "Piero", "last_name": "Carninci", "name": null }, { "creator_type": "author", "first_name": "Alistair R. R.", "last_name": "Forrest", "name": null }, { "creator_type": "author", "first_name": "Yoshihide", "last_name": "Hayashizaki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/sdata.2017.112" }, "pmcid": { "normalized": "PMC5574368" }, "pmid": { "normalized": "28850106" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Gene Expression Profiling", "descriptor_ui": "D020869", "major_topic": true }, { "descriptor": "Gene Expression Regulation", "descriptor_ui": "D005786", "major_topic": false }, { "descriptor": "Genome", "descriptor_ui": "D016678", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Promoter Regions, Genetic", "descriptor_ui": "D011401", "major_topic": false }, { "descriptor": "Species Specificity", "descriptor_ui": "D013045", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Aug 29", "date_precision": "day", "issue": "", "normalized_date": "2017-08-29", "pages": "170112", "proceedings_title": null, "publisher": "", "title": "Scientific data", "volume": "4", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "FANTOM5 CAGE profiles of human and mouse samples.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The extent to which defective innate immune responses contribute to chronic obstructive pulmonary disease (COPD) is not fully understood. Pulmonary surfactant protein A (SP-A) plays an important role in regulating innate immunity in the lungs. In this study, we hypothesised that cigarette smoke (CS) and its component acrolein might influence pulmonary innate immunity by affecting the function of SP-A. Indeed, acrolein-modified SP-A was detected in the lungs of mice exposed to CS for 1 week. To further confirm this finding, recombinant human SP-A (hSP-A) was incubated with CS extract (CSE) or acrolein and then analysed by western blotting and nanoscale liquid chromatography-matrix-assisted laser desorption/ionisation time-of-flight tandem mass spectrometry. These analyses revealed that CSE and acrolein induced hSP-A oligomerisation and that acrolein induced the modification of six residues in hSP-A: His39, His116, Cys155, Lys180, Lys221, and Cys224. These modifications had significant effects on the innate immune functions of hSP-A. CSE- or acrolein-induced modification of hSP-A significantly decreased hSP-A's ability to inhibit bacterial growth and to enhance macrophage phagocytosis. These findings suggest that CS-induced structural and functional defects in SP-A contribute to the dysfunctional innate immune responses observed in the lung during cigarette smoking.", "classifications": [ { "id": "Akaike", "label": "Group Akaike", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Rina", "last_name": "Takamiya", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Uchida", "name": null }, { "creator_type": "author", "first_name": "Takahiro", "last_name": "Shibata", "name": null }, { "creator_type": "author", "first_name": "Toshitaka", "last_name": "Maeno", "name": null }, { "creator_type": "author", "first_name": "Masaki", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Yoshiki", "last_name": "Yamaguchi", "name": null }, { "creator_type": "author", "first_name": "Shigeru", "last_name": "Ariki", "name": null }, { "creator_type": "author", "first_name": "Yoshihiro", "last_name": "Hasegawa", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Soichi", "last_name": "Miwa", "name": null }, { "creator_type": "author", "first_name": "Hiroki", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Takaaki", "last_name": "Akaike", "name": null }, { "creator_type": "author", "first_name": "Yoshio", "last_name": "Kuroki", "name": null }, { "creator_type": "author", "first_name": "Motoko", "last_name": "Takahashi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41598-017-08588-5" }, "pmcid": { "normalized": "PMC5559459" }, "pmid": { "normalized": "28814727" } }, "mesh": [ { "descriptor": "Acrolein", "descriptor_ui": "D000171", "major_topic": false }, { "descriptor": "Aldehydes", "descriptor_ui": "D000447", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "CHO Cells", "descriptor_ui": "D016466", "major_topic": false }, { "descriptor": "Cigarette Smoking", "descriptor_ui": "D000073865", "major_topic": false }, { "descriptor": "Cricetulus", "descriptor_ui": "D003412", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Macrophages", "descriptor_ui": "D008264", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Models, Biological", "descriptor_ui": "D008954", "major_topic": false }, { "descriptor": "Molecular Structure", "descriptor_ui": "D015394", "major_topic": false }, { "descriptor": "Nicotiana", "descriptor_ui": "D014026", "major_topic": false }, { "descriptor": "Phagocytosis", "descriptor_ui": "D010587", "major_topic": false }, { "descriptor": "Protein Conformation", "descriptor_ui": "D011487", "major_topic": false }, { "descriptor": "Pulmonary Surfactant-Associated Protein A", "descriptor_ui": "D037662", "major_topic": false }, { "descriptor": "RAW 264.7 Cells", "descriptor_ui": "D000067996", "major_topic": false }, { "descriptor": "Sulfhydryl Compounds", "descriptor_ui": "D013438", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Aug 16", "date_precision": "day", "issue": "1", "normalized_date": "2017-08-16", "pages": "8304", "proceedings_title": null, "publisher": "", "title": "Scientific reports", "volume": "7", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Disruption of the structural and functional features of surfactant protein A by acrolein in cigarette smoke.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Purpose: Patients with pancreatic neuroendocrine neoplasm grade-3 (PanNEN-G3) show variable responses to platinum-based chemotherapy. Recent studies indicated that PanNEN-G3 includes well-differentiated neuroendocrine tumor with G3 (NET-G3). Here, we examined the clinicopathologic and molecular features of PanNEN-G3 and assessed the responsiveness to chemotherapy and survival.Experimental Design: A total of 100 patients with PanNEN-G3 were collected from 31 institutions, and after central review characteristics of each histologic subtype [NET-G3 vs. pancreatic neuroendocrine carcinoma (NEC-G3)] were analyzed, including clinical, radiological, and molecular features. Factors that correlate with response to chemotherapy and survival were assessed.Results: Seventy patients analyzed included 21 NETs-G3 (30%) and 49 NECs-G3 (70%). NET-G3 showed lower Ki67-labeling index (LI; median 28.5%), no abnormal Rb expression (0%), and no mutated KRAS (0%), whereas NEC-G3 showed higher Ki67-LI (median 80.0%), Rb loss (54.5%), and KRAS mutations (48.7%). Chemotherapy response rate (RR), platinum-based chemotherapy RR, and prognosis differed significantly between NET-G3 and NEC-G3. Chemotherapeutic outcomes were worse in NET-G3 (P < 0.001). When we stratified PanNEN-G3 with Rb and KRAS, PanNENs-G3 with Rb loss and those with mutated KRAS showed significantly higher RRs to platinum-based chemotherapy than those without (Rb loss, 80% vs. normal Rb, 24%, P = 0.006; mutated KRAS, 77% versus wild type, 23%, P = 0.023). Rb was a predictive marker of response to platinum-based chemotherapy even in NEC-G3 (P = 0.035).Conclusions: NET-G3 and NEC-G3 showed distinct clinicopathologic characteristics. Notably, NET-G3 does not respond to platinum-based chemotherapy. Rb and KRAS are promising predictors of response to platinum-based chemotherapy for PanNEN-G3, and Rb for NEC-G3. Clin Cancer Res; 23(16); 4625-32. (c)2017 AACR.", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Susumu", "last_name": "Hijioka", "name": null }, { "creator_type": "author", "first_name": "Waki", "last_name": "Hosoda", "name": null }, { "creator_type": "author", "first_name": "Keitaro", "last_name": "Matsuo", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Ueno", "name": null }, { "creator_type": "author", "first_name": "Masayuki", "last_name": "Furukawa", "name": null }, { "creator_type": "author", "first_name": "Hideyuki", "last_name": "Yoshitomi", "name": null }, { "creator_type": "author", "first_name": "Noritoshi", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Masafumi", "last_name": "Ikeda", "name": null }, { "creator_type": "author", "first_name": "Tetsuhide", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Shoji", "last_name": "Nakamori", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Ishii", "name": null }, { "creator_type": "author", "first_name": "Yuzo", "last_name": "Kodama", "name": null }, { "creator_type": "author", "first_name": "Chigusa", "last_name": "Morizane", "name": null }, { "creator_type": "author", "first_name": "Takuji", "last_name": "Okusaka", "name": null }, { "creator_type": "author", "first_name": "Hiroaki", "last_name": "Yanagimoto", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Notohara", "name": null }, { "creator_type": "author", "first_name": "Hiroki", "last_name": "Taguchi", "name": null }, { "creator_type": "author", "first_name": "Masayuki", "last_name": "Kitano", "name": null }, { "creator_type": "author", "first_name": "Kei", "last_name": "Yane", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Maguchi", "name": null }, { "creator_type": "author", "first_name": "Yoshiaki", "last_name": "Tsuchiya", "name": null }, { "creator_type": "author", "first_name": "Izumi", "last_name": "Komoto", "name": null }, { "creator_type": "author", "first_name": "Hiroki", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Akihito", "last_name": "Tsuji", "name": null }, { "creator_type": "author", "first_name": "Syunpei", "last_name": "Hashigo", "name": null }, { "creator_type": "author", "first_name": "Yoshiaki", "last_name": "Kawaguchi", "name": null }, { "creator_type": "author", "first_name": "Tetsuya", "last_name": "Mine", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Kanno", "name": null }, { "creator_type": "author", "first_name": "Go", "last_name": "Murohisa", "name": null }, { "creator_type": "author", "first_name": "Katsuyuki", "last_name": "Miyabe", "name": null }, { "creator_type": "author", "first_name": "Tadayuki", "last_name": "Takagi", "name": null }, { "creator_type": "author", "first_name": "Nobutaka", "last_name": "Matayoshi", "name": null }, { "creator_type": "author", "first_name": "Tsukasa", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Kazuo", "last_name": "Hara", "name": null }, { "creator_type": "author", "first_name": "Masayuki", "last_name": "Imamura", "name": null }, { "creator_type": "author", "first_name": "Junji", "last_name": "Furuse", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null }, { "creator_type": "author", "first_name": "Nobumasa", "last_name": "Mizuno", "name": null } ], "identifiers": { "doi": { "normalized": "10.1158/1078-0432.ccr-16-3135" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "28455360" } }, "mesh": [ { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Aged, 80 and over", "descriptor_ui": "D000369", "major_topic": false }, { "descriptor": "Antineoplastic Combined Chemotherapy Protocols", "descriptor_ui": "D000971", "major_topic": false }, { "descriptor": "Asian People", "descriptor_ui": "D044466", "major_topic": false }, { "descriptor": "Biomarkers, Tumor", "descriptor_ui": "D014408", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Japan", "descriptor_ui": "D007564", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": true }, { "descriptor": "Neoplasm Grading", "descriptor_ui": "D060787", "major_topic": false }, { "descriptor": "Neuroendocrine Tumors", "descriptor_ui": "D018358", "major_topic": false }, { "descriptor": "Pancreas", "descriptor_ui": "D010179", "major_topic": false }, { "descriptor": "Pancreatic Neoplasms", "descriptor_ui": "D010190", "major_topic": false }, { "descriptor": "Platinum", "descriptor_ui": "D010984", "major_topic": false }, { "descriptor": "Prognosis", "descriptor_ui": "D011379", "major_topic": false }, { "descriptor": "Proto-Oncogene Proteins p21(ras)", "descriptor_ui": "D016283", "major_topic": false }, { "descriptor": "Retinoblastoma Protein", "descriptor_ui": "D016160", "major_topic": false }, { "descriptor": "Survival Analysis", "descriptor_ui": "D016019", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Aug 15", "date_precision": "day", "issue": "16", "normalized_date": "2017-08-15", "pages": "4625-4632", "proceedings_title": null, "publisher": "", "title": "Clinical cancer research : an official journal of the American Association for Cancer Research", "volume": "23", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Rb Loss and KRAS Mutation Are Predictors of the Response to Platinum-Based Chemotherapy in Pancreatic Neuroendocrine Neoplasm with Grade 3: A Japanese Multicenter Pancreatic NEN-G3 Study.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Caveolae are abundant flask-shaped invaginations of plasma membranes that buffer membrane tension through their deformation. Few quantitative studies on the deformation of caveolae have been reported. Each caveola contains approximately 150 caveolin-1 proteins. In this study, we estimated the extent of caveolar deformation by measuring the density of caveolin-1 projected onto a two-dimensional (2D) plane. The caveolin-1 in a flattened caveola is assumed to have approximately one-quarter of the density of the caveolin-1 in a flask-shaped caveola. The proportion of one-quarter-density caveolin-1 increased after increasing the tension of the plasma membrane through hypo-osmotic treatment. The one-quarter-density caveolin-1 was soluble in detergent and formed a continuous population with the caveolin-1 in the caveolae of cells under isotonic culture. The distinct, dispersed lower-density caveolin-1 was soluble in detergent and increased after the application of tension, suggesting that the hypo-osmotic tension induced the dispersion of caveolin-1 from the caveolae, possibly through flattened caveolar intermediates.", "classifications": [ { "id": "Mochizuki", "label": "Group Mochizuki", "parent": "Eiraku", "type": "group" }, { "id": "Eiraku", "label": "Team Eiraku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Masashi", "last_name": "Tachikawa", "name": null }, { "creator_type": "author", "first_name": "Nobuhiro", "last_name": "Morone", "name": null }, { "creator_type": "author", "first_name": "Yosuke", "last_name": "Senju", "name": null }, { "creator_type": "author", "first_name": "Tadao", "last_name": "Sugiura", "name": null }, { "creator_type": "author", "first_name": "Kyoko", "last_name": "Hanawa-Suetsugu", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Mochizuki", "name": null }, { "creator_type": "author", "first_name": "Shiro", "last_name": "Suetsugu", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41598-017-08259-5" }, "pmcid": { "normalized": "PMC5552771" }, "pmid": { "normalized": "28798329" } }, "mesh": [ { "descriptor": "Caveolae", "descriptor_ui": "D021941", "major_topic": false }, { "descriptor": "Caveolin 1", "descriptor_ui": "D051242", "major_topic": false }, { "descriptor": "Cell Membrane", "descriptor_ui": "D002462", "major_topic": false }, { "descriptor": "HeLa Cells", "descriptor_ui": "D006367", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Osmotic Pressure", "descriptor_ui": "D009997", "major_topic": true } ], "publication": { "conference_name": null, "date": "2017 Aug 10", "date_precision": "day", "issue": "1", "normalized_date": "2017-08-10", "pages": "7794", "proceedings_title": null, "publisher": "", "title": "Scientific reports", "volume": "7", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Measurement of caveolin-1 densities in the cell membrane for quantification of caveolar deformation after exposure to hypotonic membrane tension.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Inhibitors of Mek1/2 and Gsk3beta, known as 2i, enhance the derivation of embryonic stem (ES) cells and promote ground-state pluripotency in rodents. Here we show that the derivation of female mouse ES cells in the presence of 2i and leukaemia inhibitory factor (2i/L ES cells) results in a widespread loss of DNA methylation, including a massive erasure of genomic imprints. Despite this global loss of DNA methylation, early-passage 2i/L ES cells efficiently differentiate into somatic cells, and this process requires genome-wide de novo DNA methylation. However, the majority of imprinting control regions (ICRs) remain unmethylated in 2i/L-ES-cell-derived differentiated cells. Consistently, 2i/L ES cells exhibit impaired autonomous embryonic and placental development by tetraploid embryo complementation or nuclear transplantation. We identified the derivation conditions of female ES cells that display 2i/L-ES-cell-like transcriptional signatures while preserving gamete-derived DNA methylation and autonomous developmental potential. Upon prolonged culture, however, female ES cells exhibited ICR demethylation regardless of culture conditions. Our results provide insights into the derivation of female ES cells reminiscent of the inner cell mass of preimplantation embryos.", "classifications": [ { "id": "Yamamoto", "label": "Group Yamamoto", "parent": "Toyoshima", "type": "group" }, { "id": "Toyoshima", "label": "Team Toyoshima", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Masaki", "last_name": "Yagi", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Kishigami", "name": null }, { "creator_type": "author", "first_name": "Akito", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Katsunori", "last_name": "Semi", "name": null }, { "creator_type": "author", "first_name": "Eiji", "last_name": "Mizutani", "name": null }, { "creator_type": "author", "first_name": "Sayaka", "last_name": "Wakayama", "name": null }, { "creator_type": "author", "first_name": "Teruhiko", "last_name": "Wakayama", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Yasuhiro", "last_name": "Yamada", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/nature23286" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "28746308" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "DNA Methylation", "descriptor_ui": "D019175", "major_topic": false }, { "descriptor": "Embryonic Stem Cells", "descriptor_ui": "D053595", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Genomic Imprinting", "descriptor_ui": "D018392", "major_topic": false }, { "descriptor": "Glycogen Synthase Kinase 3 beta", "descriptor_ui": "D000071679", "major_topic": false }, { "descriptor": "Leukemia Inhibitory Factor", "descriptor_ui": "D053605", "major_topic": false }, { "descriptor": "MAP Kinase Kinase 1", "descriptor_ui": "D048369", "major_topic": false }, { "descriptor": "MAP Kinase Kinase 2", "descriptor_ui": "D048370", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Aug 10", "date_precision": "day", "issue": "7666", "normalized_date": "2017-08-10", "pages": "224-227", "proceedings_title": null, "publisher": "", "title": "Nature", "volume": "548", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Derivation of ground-state female ES cells maintaining gamete-derived DNA methylation.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Genome-wide CRISPR-based knockout (CRISPR-KO) screening is an emerging technique which enables systematic genetic analysis of a cellular or molecular phenotype in question. Continuous improvements, such as modifications to the guide RNA (gRNA) scaffold and the development of gRNA on-target prediction algorithms, have since been made to increase their screening performance. We compared the performance of three available second-generation human genome-wide CRISPR-KO libraries that included at least one of the improvements, and examined the effect of gRNA scaffold, number of gRNAs per gene and number of replicates on screen performance. We identified duplicated screens using a library with 6 gRNAs per gene as providing the best trade-off. Despite the improvements, we found that each improved library still has library-specific false negatives and, for the first time, estimated the false negative rates of CRISPR-KO screens, which are between 10% and 20%. Our newly-defined optimal screening parameters would be helpful in designing screens and constructing bespoke gRNA libraries.", "classifications": [ { "id": "Yusa", "label": "Group Yusa", "parent": "Eiraku", "type": "group" }, { "id": "Eiraku", "label": "Team Eiraku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Swee Hoe", "last_name": "Ong", "name": null }, { "creator_type": "author", "first_name": "Yilong", "last_name": "Li", "name": null }, { "creator_type": "author", "first_name": "Hiroko", "last_name": "Koike-Yusa", "name": null }, { "creator_type": "author", "first_name": "Kosuke", "last_name": "Yusa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41598-017-07827-z" }, "pmcid": { "normalized": "PMC5547152" }, "pmid": { "normalized": "28785007" } }, "mesh": [ { "descriptor": "Algorithms", "descriptor_ui": "D000465", "major_topic": false }, { "descriptor": "CRISPR-Cas Systems", "descriptor_ui": "D064113", "major_topic": false }, { "descriptor": "Gene Knockout Techniques", "descriptor_ui": "D055786", "major_topic": false }, { "descriptor": "Gene Library", "descriptor_ui": "D015723", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "RNA, Guide, CRISPR-Cas Systems", "descriptor_ui": "D000094704", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Aug 7", "date_precision": "day", "issue": "1", "normalized_date": "2017-08-07", "pages": "7384", "proceedings_title": null, "publisher": "", "title": "Scientific reports", "volume": "7", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Optimised metrics for CRISPR-KO screens with second-generation gRNA libraries.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Myocardial atrophy is a wasting of cardiac muscle due to hemodynamic unloading. Doxorubicin is a highly effective anticancer agent but also induces myocardial atrophy through a largely unknown mechanism. Here, we demonstrate that inhibiting transient receptor potential canonical 3 (TRPC3) channels abolishes doxorubicin-induced myocardial atrophy in mice. Doxorubicin increased production of ROS in rodent cardiomyocytes through hypoxic stress–mediated upregulation of NADPH oxidase 2 (Nox2), which formed a stable complex with TRPC3. Cardiomyocyte-specific expression of TRPC3 C-terminal minipeptide inhibited TRPC3-Nox2 coupling and suppressed doxorubicin-induced reduction of myocardial cell size and left ventricular (LV) dysfunction, along with its upregulation of Nox2 and oxidative stress, without reducing hypoxic stress. Voluntary exercise, an effective treatment to prevent doxorubicin-induced cardiotoxicity, also downregulated the TRPC3-Nox2 complex and promoted volume load–induced LV compliance, as demonstrated in TRPC3-deficient hearts. These results illustrate the impact of TRPC3 on LV compliance and flexibility and, focusing on the TRPC3-Nox2 complex, provide a strategy for prevention of doxorubicin-induced cardiomyopathy.", "classifications": [ { "id": "Nishida", "label": "Group Nishida", "parent": "Nishida", "type": "group" }, { "id": "Nishimura", "label": "Group Nishimura", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Tsukasa", "last_name": "Shimauchi", "name": null }, { "creator_type": "author", "first_name": "Takuro", "last_name": "Numaga-Tomita", "name": null }, { "creator_type": "author", "first_name": "Tomoya", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Akiyuki", "last_name": "Nishimura", "name": null }, { "creator_type": "author", "first_name": "Ryosuke", "last_name": "Matsukane", "name": null }, { "creator_type": "author", "first_name": "Sayaka", "last_name": "Oda", "name": null }, { "creator_type": "author", "first_name": "Sumio", "last_name": "Hoka", "name": null }, { "creator_type": "author", "first_name": "Tomomi", "last_name": "Ide", "name": null }, { "creator_type": "author", "first_name": "Norimichi", "last_name": "Koitabashi", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Uchida", "name": null }, { "creator_type": "author", "first_name": "Hideki", "last_name": "Sumimoto", "name": null }, { "creator_type": "author", "first_name": "Yasuo", "last_name": "Mori", "name": null }, { "creator_type": "author", "first_name": "Motohiro", "last_name": "Nishida", "name": null } ], "identifiers": { "doi": { "normalized": "10.1172/jci.insight.93358" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "28768915" } }, "mesh": [], "publication": { "conference_name": null, "date": "2017-08-03", "date_precision": "day", "issue": "15", "normalized_date": "2017-08-03", "pages": "", "proceedings_title": null, "publisher": "", "title": "JCI Insight", "volume": "2", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "TRPC3-Nox2 complex mediates doxorubicin-induced myocardial atrophy.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "As stimulated emission depletion (STED) microscopy can provide structural details of cells with an optical resolution beyond the diffraction limit, it has become an indispensable tool in cell biology. However, the intense STED laser beam usually causes rapid photobleaching of the employed fluorescent dyes, which significantly limits the utility of STED microscopy from a practical perspective. Herein we report a new design of super-photostable dye, PhoxBright 430 (PB430), comprising a fully ring-fused pi-conjugated skeleton with an electron-accepting phosphole P-oxide unit. We previously developed a super-photostable dye C-Naphox by combining the phosphole unit with an electron-donating triphenylamine moiety. In PB430, removal of the amino group alters the transition type from intramolecular charge transfer character to pi-pi* transition character, which gives rise to intense fluorescence insensitive to molecular environment in terms of fluorescence colors and intensity, and bright fluorescence even in aqueous media. PB430 also furnishes high solubility in water, and is capable of labeling proteins with maintaining high fluorescence quantum yields. This dye exhibits outstanding resistance to photoirradiation even under the STED conditions and allows continuous acquisition of STED images. Indeed, using a PB430-conjugated antibody, we succeed in attaining a 3-D reconstruction of super-resolution STED images as well as photostability-based multicolor STED imaging of fluorescently labeled cytoskeletal structures.", "classifications": [ { "id": "Sato", "label": "Group Sato", "parent": "Tsuchiya", "type": "group" }, { "id": "Tsuchiya", "label": "Team Tsuchiya", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Chenguang", "last_name": "Wang", "name": null }, { "creator_type": "author", "first_name": "Masayasu", "last_name": "Taki", "name": null }, { "creator_type": "author", "first_name": "Yoshikatsu", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Aiko", "last_name": "Fukazawa", "name": null }, { "creator_type": "author", "first_name": "Tetsuya", "last_name": "Higashiyama", "name": null }, { "creator_type": "author", "first_name": "Shigehiro", "last_name": "Yamaguchi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/jacs.7b04418" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "28741935" } }, "mesh": [ { "descriptor": "Fluorescent Dyes", "descriptor_ui": "D005456", "major_topic": false }, { "descriptor": "HeLa Cells", "descriptor_ui": "D006367", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Microscopy, Fluorescence", "descriptor_ui": "D008856", "major_topic": false }, { "descriptor": "Molecular Conformation", "descriptor_ui": "D008968", "major_topic": false }, { "descriptor": "Optical Imaging", "descriptor_ui": "D061848", "major_topic": false }, { "descriptor": "Phosphorus Compounds", "descriptor_ui": "D017553", "major_topic": false }, { "descriptor": "Photobleaching", "descriptor_ui": "D038761", "major_topic": false }, { "descriptor": "Quantum Theory", "descriptor_ui": "D011789", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Aug 2", "date_precision": "day", "issue": "30", "normalized_date": "2017-08-02", "pages": "10374-10381", "proceedings_title": null, "publisher": "", "title": "Journal of the American Chemical Society", "volume": "139", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Super-Photostable Phosphole-Based Dye for Multiple-Acquisition Stimulated Emission Depletion Imaging.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "MOTIVATION: The analysis of RNA-Seq data from individual differentiating cells enables us to reconstruct the differentiation process and the degree of differentiation (in pseudo-time) of each cell. Such analyses can reveal detailed expression dynamics and functional relationships for differentiation. To further elucidate differentiation processes, more insight into gene regulatory networks is required. The pseudo-time can be regarded as time information and, therefore, single-cell RNA-Seq data are time-course data with high time resolution. Although time-course data are useful for inferring networks, conventional inference algorithms for such data suffer from high time complexity when the number of samples and genes is large. Therefore, a novel algorithm is necessary to infer networks from single-cell RNA-Seq during differentiation. RESULTS: In this study, we developed the novel and efficient algorithm SCODE to infer regulatory networks, based on ordinary differential equations. We applied SCODE to three single-cell RNA-Seq datasets and confirmed that SCODE can reconstruct observed expression dynamics. We evaluated SCODE by comparing its inferred networks with use of a DNaseI-footprint based network. The performance of SCODE was best for two of the datasets and nearly best for the remaining dataset. We also compared the runtimes and showed that the runtimes for SCODE are significantly shorter than for alternatives. Thus, our algorithm provides a promising approach for further single-cell differentiation analyses. AVAILABILITY AND IMPLEMENTATION: The R source code of SCODE is available at https://github.com/hmatsu1226/SCODE. CONTACT: hirotaka.matsumoto@riken.jp. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.", "classifications": [ { "id": "Nikaido", "label": "Group Nikaido", "parent": "Fujiwara", "type": "group" }, { "id": "Fujiwara", "label": "Team Fujiwara", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Hirotaka", "last_name": "Matsumoto", "name": null }, { "creator_type": "author", "first_name": "Hisanori", "last_name": "Kiryu", "name": null }, { "creator_type": "author", "first_name": "Chikara", "last_name": "Furusawa", "name": null }, { "creator_type": "author", "first_name": "Minoru S. H.", "last_name": "Ko", "name": null }, { "creator_type": "author", "first_name": "Shigeru B. H.", "last_name": "Ko", "name": null }, { "creator_type": "author", "first_name": "Norio", "last_name": "Gouda", "name": null }, { "creator_type": "author", "first_name": "Tetsutaro", "last_name": "Hayashi", "name": null }, { "creator_type": "author", "first_name": "Itoshi", "last_name": "Nikaido", "name": null } ], "identifiers": { "doi": { "normalized": "10.1093/bioinformatics/btx194" }, "pmcid": { "normalized": "PMC5860123" }, "pmid": { "normalized": "28379368" } }, "mesh": [ { "descriptor": "Algorithms", "descriptor_ui": "D000465", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Gene Regulatory Networks", "descriptor_ui": "D053263", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Sequence Analysis, RNA", "descriptor_ui": "D017423", "major_topic": false }, { "descriptor": "Single-Cell Analysis", "descriptor_ui": "D059010", "major_topic": false }, { "descriptor": "Software", "descriptor_ui": "D012984", "major_topic": true } ], "publication": { "conference_name": null, "date": "2017 Aug 1", "date_precision": "day", "issue": "15", "normalized_date": "2017-08-01", "pages": "2314-2321", "proceedings_title": null, "publisher": "", "title": "Bioinformatics (Oxford, England)", "volume": "33", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "SCODE: an efficient regulatory network inference algorithm from single-cell RNA-Seq during differentiation.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Primordial germ cells (PGCs), undifferentiated embryonic germ cells, are the only cells that have the ability to become gametes and to reacquire totipotency upon fertilization. It is generally understood that the development of PGCs proceeds through the expression of germ cell-specific transcription factors and characteristic epigenomic changes. However, little is known about the properties of PGCs at the metabolite and protein levels, which are directly responsible for the control of cell function. Here, we report the distinct energy metabolism of PGCs compared with that of embryonic stem cells. Specifically, we observed remarkably enhanced oxidative phosphorylation (OXPHOS) and decreased glycolysis in embryonic day 13.5 (E13.5) PGCs, a pattern that was gradually established during PGC differentiation. We also demonstrate that glycolysis and OXPHOS are important for the control of PGC reprogramming and specification of pluripotent stem cells (PSCs) into PGCs in culture. Our findings about the unique metabolic property of PGCs provide insights into our understanding of the importance of distinct facets of energy metabolism for switching PGC and PSC status.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yohei", "last_name": "Hayashi", "name": null }, { "creator_type": "author", "first_name": "Kei", "last_name": "Otsuka", "name": null }, { "creator_type": "author", "first_name": "Masayuki", "last_name": "Ebina", "name": null }, { "creator_type": "author", "first_name": "Kaori", "last_name": "Igarashi", "name": null }, { "creator_type": "author", "first_name": "Asuka", "last_name": "Takehara", "name": null }, { "creator_type": "author", "first_name": "Mitsuyo", "last_name": "Matsumoto", "name": null }, { "creator_type": "author", "first_name": "Akio", "last_name": "Kanai", "name": null }, { "creator_type": "author", "first_name": "Kazuhiko", "last_name": "Igarashi", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Yasuhisa", "last_name": "Matsui", "name": null } ], "identifiers": { "doi": { "normalized": "10.1073/pnas.1620915114" }, "pmcid": { "normalized": "PMC5547595" }, "pmid": { "normalized": "28716939" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Embryonic Germ Cells", "descriptor_ui": "D000066473", "major_topic": false }, { "descriptor": "Embryonic Stem Cells", "descriptor_ui": "D053595", "major_topic": false }, { "descriptor": "Energy Metabolism", "descriptor_ui": "D004734", "major_topic": false }, { "descriptor": "Gene Expression Regulation", "descriptor_ui": "D005786", "major_topic": false }, { "descriptor": "Glycolysis", "descriptor_ui": "D006019", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Transgenic", "descriptor_ui": "D008822", "major_topic": false }, { "descriptor": "Mitochondria", "descriptor_ui": "D008928", "major_topic": false }, { "descriptor": "Oxidative Phosphorylation", "descriptor_ui": "D010085", "major_topic": true }, { "descriptor": "Pluripotent Stem Cells", "descriptor_ui": "D039904", "major_topic": false }, { "descriptor": "Proteome", "descriptor_ui": "D020543", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Aug 1", "date_precision": "day", "issue": "31", "normalized_date": "2017-08-01", "pages": "8289-8294", "proceedings_title": null, "publisher": "", "title": "Proceedings of the National Academy of Sciences of the United States of America", "volume": "114", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Distinct requirements for energy metabolism in mouse primordial germ cells and their reprogramming to embryonic germ cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Deregulated activation of RAS/extracellular signal-regulated kinase (ERK) signaling and defects in retinoic acid receptor (RAR) signaling are both implicated in many types of cancers. However, interrelationships between these alterations in regulating cancer cell fates have not been fully elucidated. Here, we show that RAS/ERK and RAR signaling pathways antagonistically interact with each other to regulate colorectal cancer (CRC) cell fates. We show that RAR signaling activation promotes spontaneous differentiation of CRC cells, while ERK activation suppresses it. Our microarray analyses identify genes whose expression levels are upregulated by RAR signaling. Notably, one of these genes, MKP4, encoding a member of dual-specificity phosphatases for mitogen-activated protein (MAP) kinases, mediates ERK inactivation upon RAR activation, thereby promoting the differentiation of CRC cells. Moreover, our results also show that RA induction of RAR target genes is suppressed by the ERK pathway activation. This suppression results from the inhibition of RAR transcriptional activity, which is shown to be mediated through an RIP140/histone deacetylase (HDAC)-mediated mechanism. These results identify antagonistic interactions between RAS/ERK and RAR signaling in the cell fate decision of CRC cells and define their underlying molecular mechanisms.", "classifications": [ { "id": "Yamamoto", "label": "Group Yamamoto", "parent": "Toyoshima", "type": "group" }, { "id": "Toyoshima", "label": "Team Toyoshima", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Masamichi", "last_name": "Imajo", "name": null }, { "creator_type": "author", "first_name": "Kunio", "last_name": "Kondoh", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Kei", "last_name": "Nakayama", "name": null }, { "creator_type": "author", "first_name": "May", "last_name": "Nakajima-Koyama", "name": null }, { "creator_type": "author", "first_name": "Eisuke", "last_name": "Nishida", "name": null } ], "identifiers": { "doi": { "normalized": "10.1128/mcb.00012-17" }, "pmcid": { "normalized": "PMC5514455" }, "pmid": { "normalized": "28483913" } }, "mesh": [ { "descriptor": "Adaptor Proteins, Signal Transducing", "descriptor_ui": "D048868", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Colon", "descriptor_ui": "D003106", "major_topic": false }, { "descriptor": "Colorectal Neoplasms", "descriptor_ui": "D015179", "major_topic": false }, { "descriptor": "Dual-Specificity Phosphatases", "descriptor_ui": "D054637", "major_topic": false }, { "descriptor": "Extracellular Signal-Regulated MAP Kinases", "descriptor_ui": "D048049", "major_topic": false }, { "descriptor": "Gene Expression Regulation, Neoplastic", "descriptor_ui": "D015972", "major_topic": false }, { "descriptor": "Histone Deacetylases", "descriptor_ui": "D006655", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mitogen-Activated Protein Kinase Phosphatases", "descriptor_ui": "D054639", "major_topic": false }, { "descriptor": "Nuclear Proteins", "descriptor_ui": "D009687", "major_topic": false }, { "descriptor": "Nuclear Receptor Interacting Protein 1", "descriptor_ui": "D000078723", "major_topic": false }, { "descriptor": "Promoter Regions, Genetic", "descriptor_ui": "D011401", "major_topic": false }, { "descriptor": "Receptors, Retinoic Acid", "descriptor_ui": "D018168", "major_topic": false }, { "descriptor": "Rectum", "descriptor_ui": "D012007", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": true } ], "publication": { "conference_name": null, "date": "2017 Aug 1", "date_precision": "day", "issue": "15", "normalized_date": "2017-08-01", "pages": "", "proceedings_title": null, "publisher": "", "title": "Molecular and cellular biology", "volume": "37", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Antagonistic Interactions between Extracellular Signal-Regulated Kinase Mitogen-Activated Protein Kinase and Retinoic Acid Receptor Signaling in Colorectal Cancer Cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Glial cell line-derived neurotrophic factor (GDNF) positively regulates the development and maintenance of in vitro dopaminergic neurons. However, the in vivo influences of GDNF signals on the brain dopamine system are controversial and not fully defined. To address this question, we analyzed dopaminergic phenotypes of the transgenic mice that overexpress GDNF under the control of the glial Gfap promoter. Compared with wild-type, the GDNF transgenic mice contained higher levels of GDNF protein and phosphorylated RET receptors in the brain. However, there were reductions in the levels of tyrosine hydroxylase (TH), dopamine, and its metabolite homovanillic acid in the striatum of transgenic mice. The TH reduction appeared to occur during postnatal development. Immunohistochemistry revealed that striatal TH density was reduced in transgenic mice with no apparent signs of neurodegeneration. In agreement with these neurochemical traits, basal levels of extracellular dopamine and high K+-induced dopamine efflux were decreased in the striatum of transgenic mice. We also explored the influences of GDNF overexpression on lomomotor behavior. GDNF transgenic mice exhibited lower stereotypy and rearing in a novel environment compared with wild-type mice. These results suggest that chronic overexpression of GDNF in brain astrocytes exerts an opposing influence on nigrostriatal dopamine metabolism and neurotransmission.", "classifications": [ { "id": "Enomoto", "label": "Group Enomoto", "parent": "Enomoto", "type": "group" }, { "id": "Enomoto", "label": "Team Enomoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Hidekazu", "last_name": "Sotoyama", "name": null }, { "creator_type": "author", "first_name": "Yuriko", "last_name": "Iwakura", "name": null }, { "creator_type": "author", "first_name": "Kanako", "last_name": "Oda", "name": null }, { "creator_type": "author", "first_name": "Toshikuni", "last_name": "Sasaoka", "name": null }, { "creator_type": "author", "first_name": "Nobuyuki", "last_name": "Takei", "name": null }, { "creator_type": "author", "first_name": "Akiyoshi", "last_name": "Kakita", "name": null }, { "creator_type": "author", "first_name": "Hideki", "last_name": "Enomoto", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Nawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.neulet.2017.06.005" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "28645787" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Corpus Striatum", "descriptor_ui": "D003342", "major_topic": false }, { "descriptor": "Dopamine", "descriptor_ui": "D004298", "major_topic": false }, { "descriptor": "Glial Cell Line-Derived Neurotrophic Factor", "descriptor_ui": "D051100", "major_topic": false }, { "descriptor": "Locomotion", "descriptor_ui": "D008124", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Transgenic", "descriptor_ui": "D008822", "major_topic": false }, { "descriptor": "Phenotype", "descriptor_ui": "D010641", "major_topic": false }, { "descriptor": "Synaptic Transmission", "descriptor_ui": "D009435", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Jul 27", "date_precision": "day", "issue": "", "normalized_date": "2017-07-27", "pages": "99-106", "proceedings_title": null, "publisher": "", "title": "Neuroscience letters", "volume": "654", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Striatal hypodopamine phenotypes found in transgenic mice that overexpress glial cell line-derived neurotrophic factor.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The Pd-catalyzed desulfonative cross-coupling reaction of benzylic sulfone derivatives with 1,3-oxazoles via a deprotonative pathway has been developed. Broad substrate scope for both sulfone and 1,3-oxazole partners is observed, affording a variety of 1,3-oxazole-containing triarylmethanes. Sulfone partners that are primary benzylic, secondary benzylic, and benzhydryl are all effective. Using this method, the straightforward synthesis of multiply arylated structures has been demonstrated.", "classifications": [ { "id": "Nanbo", "label": "Group Nanbo", "parent": "Tsuchiya", "type": "group" }, { "id": "Tsuchiya", "label": "Team Tsuchiya", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Jacky C.-H.", "last_name": "Yim", "name": null }, { "creator_type": "author", "first_name": "Masakazu", "last_name": "Nambo", "name": null }, { "creator_type": "author", "first_name": "Cathleen M.", "last_name": "Crudden", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/acs.orglett.7b01510" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "28665623" } }, "mesh": [], "publication": { "conference_name": null, "date": "2017 Jul 21", "date_precision": "day", "issue": "14", "normalized_date": "2017-07-21", "pages": "3715-3718", "proceedings_title": null, "publisher": "", "title": "Organic letters", "volume": "19", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Pd-Catalyzed Desulfonative Cross-Coupling of Benzylic Sulfone Derivatives with 1,3-Oxazoles.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Reactive sulfur species (RSS) modulate protein functions via S-polysulfidation of reactive Cys residues. Here, we report that Ca(2+)/calmodulin (CaM)-dependent protein kinase IV (CaMKIV) was reversibly inactivated by RSS via polysulfidation of the active-site Cys residue. CaMKIV is phosphorylated at Thr(196) by its upstream CaMK kinase (CaMKK), resulting in the induction of its full activity. In vitro incubation of CaMKIV with the exogenous RSS donors Na(2)S (n) (n = 2-4) resulted in dose-dependent inhibition of the CaMKK-induced phospho-Thr(196) and consequent inactivation of the enzyme activity. Conversely, mutated CaMKIV (C198V) was refractory to the Na(2)S (n) -induced enzyme inhibition. A biotin-polyethylene glycol-conjugated maleimide capture assay revealed that Cys(198) in CaMKIV represents a target for S-polysulfidation. Furthermore, phosho-Thr(196) and CaMKIV activity were inhibited by incubation with cysteine hydropersulfide, a newly identified RSS that is generated from cystine by cystathionine-gamma-lyase. In transfected cells expressing CaMKIV, ionomycin-induced CaMKIV phosphorylation at Thr(196) was decreased upon treatment with either Na(2)S(4) or the endoplasmic reticulum (ER) stress inducer thapsigargin, whereas cells expressing mutant CaMKIV (C198V) were resistant to this treatment. In addition, the ionomycin-induced phospho-Thr(196) of endogenous CaMKIV was also inhibited by treatment either with Na(2)S(4) or thapsigargin in Jurkat T lymphocytes. Taken together, these data define a novel signaling function for intracellular RSS in inhibiting CaMKIV activity via S-polysulfidation of its Cys(198) during the response to ER stress.", "classifications": [ { "id": "Akaike", "label": "Group Akaike", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Tsuyoshi", "last_name": "Takata", "name": null }, { "creator_type": "author", "first_name": "Hideshi", "last_name": "Ihara", "name": null }, { "creator_type": "author", "first_name": "Naoya", "last_name": "Hatano", "name": null }, { "creator_type": "author", "first_name": "Yukihiro", "last_name": "Tsuchiya", "name": null }, { "creator_type": "author", "first_name": "Takaaki", "last_name": "Akaike", "name": null }, { "creator_type": "author", "first_name": "Yasuo", "last_name": "Watanabe", "name": null } ], "identifiers": { "doi": { "normalized": "10.1042/bcj20170092" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "28637792" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Calcium-Calmodulin-Dependent Protein Kinase Type 4", "descriptor_ui": "D054734", "major_topic": false }, { "descriptor": "Cysteine", "descriptor_ui": "D003545", "major_topic": false }, { "descriptor": "Endoplasmic Reticulum Stress", "descriptor_ui": "D059865", "major_topic": false }, { "descriptor": "Enzyme Activation", "descriptor_ui": "D004789", "major_topic": false }, { "descriptor": "HEK293 Cells", "descriptor_ui": "D057809", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Jurkat Cells", "descriptor_ui": "D019169", "major_topic": false }, { "descriptor": "Mass Spectrometry", "descriptor_ui": "D013058", "major_topic": false }, { "descriptor": "Mutant Proteins", "descriptor_ui": "D050505", "major_topic": false }, { "descriptor": "Phosphorylation", "descriptor_ui": "D010766", "major_topic": false }, { "descriptor": "Phosphothreonine", "descriptor_ui": "D010769", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Sulfides", "descriptor_ui": "D013440", "major_topic": false }, { "descriptor": "Sulfur", "descriptor_ui": "D013455", "major_topic": false }, { "descriptor": "Thapsigargin", "descriptor_ui": "D019284", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Jul 17", "date_precision": "day", "issue": "15", "normalized_date": "2017-07-17", "pages": "2547-2562", "proceedings_title": null, "publisher": "", "title": "The Biochemical journal", "volume": "474", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Reactive sulfur species inactivate Ca(2+)/calmodulin-dependent protein kinase IV via S-polysulfidation of its active-site cysteine residue.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Boolean network models describe genetic, neural, and social dynamics in complex networks, where the dynamics depend generally on network topology. Fixed points in a genetic regulatory network are typically considered to correspond to cell types in an organism. We prove that the expected number of fixed points in a Boolean network, with Boolean functions drawn from probability distributions that are not required to be uniform or identical, is one, and is independent of network topology if only a feedback arc set satisfies a stochastic neutrality condition. We also demonstrate that the expected number is increased by the predominance of positive feedback in a cycle.", "classifications": [ { "id": "Mochizuki", "label": "Group Mochizuki", "parent": "Eiraku", "type": "group" }, { "id": "Eiraku", "label": "Team Eiraku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Fumito", "last_name": "Mori", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Mochizuki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1103/physrevlett.119.028301" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "28753377" } }, "mesh": [], "publication": { "conference_name": null, "date": "2017 Jul 14", "date_precision": "day", "issue": "2", "normalized_date": "2017-07-14", "pages": "028301", "proceedings_title": null, "publisher": "", "title": "Physical review letters", "volume": "119", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Expected Number of Fixed Points in Boolean Networks with Arbitrary Topology.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Type XVII collagen (COL17) is a transmembrane protein located at the epidermal basement membrane zone. COL17 deficiency results in premature hair aging phenotypes and in junctional epidermolysis bullosa. Here, we show that COL17 plays a central role in regulating interfollicular epidermis (IFE) proliferation. Loss of COL17 leads to transient IFE hypertrophy in neonatal mice owing to aberrant Wnt signaling. The replenishment of COL17 in the neonatal epidermis of COL17-null mice reverses the proliferative IFE phenotype and the altered Wnt signaling. Physical aging abolishes membranous COL17 in IFE basal cells because of inactive atypical protein kinase C signaling and also induces epidermal hyperproliferation. The overexpression of human COL17 in aged mouse epidermis suppresses IFE hypertrophy. These findings demonstrate that COL17 governs IFE proliferation of neonatal and aged skin in distinct ways. Our study indicates that COL17 could be an important target of anti-aging strategies in the skin.", "classifications": [ { "id": "Nagayama", "label": "Group Nagayama", "parent": "Fujiwara", "type": "group" }, { "id": "Fujiwara", "label": "Team Fujiwara", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Mika", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Ken", "last_name": "Natsuga", "name": null }, { "creator_type": "author", "first_name": "Wataru", "last_name": "Nishie", "name": null }, { "creator_type": "author", "first_name": "Yasuaki", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Giacomo", "last_name": "Donati", "name": null }, { "creator_type": "author", "first_name": "Shotaro", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Yu", "last_name": "Fujimura", "name": null }, { "creator_type": "author", "first_name": "Tadasuke", "last_name": "Tsukiyama", "name": null }, { "creator_type": "author", "first_name": "Hideyuki", "last_name": "Ujiie", "name": null }, { "creator_type": "author", "first_name": "Satoru", "last_name": "Shinkuma", "name": null }, { "creator_type": "author", "first_name": "Hideki", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Masamoto", "last_name": "Murakami", "name": null }, { "creator_type": "author", "first_name": "Michitaka", "last_name": "Ozaki", "name": null }, { "creator_type": "author", "first_name": "Masaharu", "last_name": "Nagayama", "name": null }, { "creator_type": "author", "first_name": "Fiona M.", "last_name": "Watt", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Shimizu", "name": null } ], "identifiers": { "doi": { "normalized": "10.7554/elife.26635" }, "pmcid": { "normalized": "PMC5505703" }, "pmid": { "normalized": "28693719" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Autoantigens", "descriptor_ui": "D001324", "major_topic": false }, { "descriptor": "Cell Proliferation", "descriptor_ui": "D049109", "major_topic": true }, { "descriptor": "Collagen Type XVII", "descriptor_ui": "D000097805", "major_topic": false }, { "descriptor": "Epidermis", "descriptor_ui": "D004817", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Mice, Transgenic", "descriptor_ui": "D008822", "major_topic": false }, { "descriptor": "Non-Fibrillar Collagens", "descriptor_ui": "D024041", "major_topic": false }, { "descriptor": "Wnt Signaling Pathway", "descriptor_ui": "D060449", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Jul 11", "date_precision": "day", "issue": "", "normalized_date": "2017-07-11", "pages": "e26635", "proceedings_title": null, "publisher": "", "title": "eLife", "volume": "6", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Type XVII collagen coordinates proliferation in the interfollicular epidermis.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Pluripotent stem cells can undergo repeated self-renewal while retaining genetic integrity, but they occasionally acquire aneuploidy during long-term culture, which is a practical obstacle for medical applications of human pluripotent stem cells. In this study, we explored the biological roles of ABR, a regulator of RHO family small GTPases, and found that it has pivotal roles during mitotic processes in human embryonic stem cells (hESCs). Although ABR has been shown to be involved in dissociation-induced hESC apoptosis, it does not appear to have direct effects on cell survival unless cell-cell contact is impaired. Instead, we found that it is important for faithful hESC division. Mechanistically, ABR depletion compromised centrosome dynamics and predisposed the cell to chromosome misalignment and missegregation, which raised the frequency of aneuploidy. These results provide insights into the mechanisms that support the genetic integrity of self-renewing hESCs.", "classifications": [ { "id": "Eiraku", "label": "Group Eiraku", "parent": "Eiraku", "type": "group" }, { "id": "Eiraku", "label": "Team Eiraku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Masatoshi", "last_name": "Ohgushi", "name": null }, { "creator_type": "author", "first_name": "Maki", "last_name": "Minaguchi", "name": null }, { "creator_type": "author", "first_name": "Mototsugu", "last_name": "Eiraku", "name": null }, { "creator_type": "author", "first_name": "Yoshiki", "last_name": "Sasai", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.stemcr.2017.05.003" }, "pmcid": { "normalized": "PMC5511046" }, "pmid": { "normalized": "28579391" } }, "mesh": [ { "descriptor": "Aneuploidy", "descriptor_ui": "D000782", "major_topic": false }, { "descriptor": "Apoptosis", "descriptor_ui": "D017209", "major_topic": false }, { "descriptor": "Cell Communication", "descriptor_ui": "D002450", "major_topic": false }, { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "G2 Phase Cell Cycle Checkpoints", "descriptor_ui": "D059565", "major_topic": false }, { "descriptor": "Gene Deletion", "descriptor_ui": "D017353", "major_topic": false }, { "descriptor": "GTPase-Activating Proteins", "descriptor_ui": "D020690", "major_topic": false }, { "descriptor": "Human Embryonic Stem Cells", "descriptor_ui": "D000066449", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "M Phase Cell Cycle Checkpoints", "descriptor_ui": "D059566", "major_topic": false }, { "descriptor": "Mitosis", "descriptor_ui": "D008938", "major_topic": true }, { "descriptor": "rho GTP-Binding Proteins", "descriptor_ui": "D020741", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Jul 11", "date_precision": "day", "issue": "1", "normalized_date": "2017-07-11", "pages": "58-66", "proceedings_title": null, "publisher": "", "title": "Stem cell reports", "volume": "9", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "A RHO Small GTPase Regulator ABR Secures Mitotic Fidelity in Human Embryonic Stem Cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "In mice, various instinctive behaviors can be triggered by olfactory input. Despite growing knowledge of the brain regions involved in such behaviors, the organization of the neural circuits that convert olfactory input into stereotyped behavioral output remains poorly understood. Here, we mapped the neural circuit responsible for enhancing sexual receptivity of female mice by a male pheromone, exocrine gland-secreting peptide 1 (ESP1). We revealed specific neural types and pathways by which ESP1 information is conveyed from the peripheral receptive organ to the motor-regulating midbrain via the amygdala-hypothalamus axis. In the medial amygdala, a specific type of projection neurons gated ESP1 signals to the ventromedial hypothalamus (VMH) in a sex-dependent manner. In the dorsal VMH, which has been associated with defensive behaviors, a selective neural subpopulation discriminately mediated ESP1 information from a predator cue. Together, our data illuminate a labeled-line organization for controlling pheromone-mediated sexual behavioral output in female mice.", "classifications": [ { "id": "Miyamichi", "label": "Group Miyamichi", "parent": "Enomoto", "type": "group" }, { "id": "Enomoto", "label": "Team Enomoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Kentaro K.", "last_name": "Ishii", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Osakada", "name": null }, { "creator_type": "author", "first_name": "Hiromi", "last_name": "Mori", "name": null }, { "creator_type": "author", "first_name": "Nobuhiko", "last_name": "Miyasaka", "name": null }, { "creator_type": "author", "first_name": "Yoshihiro", "last_name": "Yoshihara", "name": null }, { "creator_type": "author", "first_name": "Kazunari", "last_name": "Miyamichi", "name": null }, { "creator_type": "author", "first_name": "Kazushige", "last_name": "Touhara", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.neuron.2017.05.038" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "28648498" } }, "mesh": [ { "descriptor": "Amygdala", "descriptor_ui": "D000679", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cues", "descriptor_ui": "D003463", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Hypothalamus", "descriptor_ui": "D007031", "major_topic": false }, { "descriptor": "Intercellular Signaling Peptides and Proteins", "descriptor_ui": "D036341", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mesencephalon", "descriptor_ui": "D008636", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Transgenic", "descriptor_ui": "D008822", "major_topic": false }, { "descriptor": "Nerve Net", "descriptor_ui": "D009415", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Predatory Behavior", "descriptor_ui": "D011235", "major_topic": false }, { "descriptor": "Proteins", "descriptor_ui": "D011506", "major_topic": false }, { "descriptor": "Sex Attractants", "descriptor_ui": "D012724", "major_topic": false }, { "descriptor": "Sex Characteristics", "descriptor_ui": "D012727", "major_topic": false }, { "descriptor": "Sexual Behavior, Animal", "descriptor_ui": "D012726", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Jul 5", "date_precision": "day", "issue": "1", "normalized_date": "2017-07-05", "pages": "123-137.e8", "proceedings_title": null, "publisher": "", "title": "Neuron", "volume": "95", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "A Labeled-Line Neural Circuit for Pheromone-Mediated Sexual Behaviors in Mice.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The expansion of primordial germ cells (PGCs), the precursors for the oocytes and spermatozoa, is a key challenge in reproductive biology/medicine. Using a chemical screening exploiting PGC-like cells (PGCLCs) induced from mouse embryonic stem cells (ESCs), we here identify key signaling pathways critical for PGCLC proliferation. We show that the combinatorial application of Forskolin and Rolipram, which stimulate cAMP signaling via different mechanisms, expands PGCLCs up to ~50-fold in culture. The expanded PGCLCs maintain robust capacity for spermatogenesis, rescuing the fertility of infertile mice. Strikingly, during expansion, PGCLCs comprehensively erase their DNA methylome, including parental imprints, in a manner that precisely recapitulates genome-wide DNA demethylation in gonadal germ cells, while essentially maintaining their identity as sexually uncommitted PGCs, apparently through appropriate histone modifications. By establishing a paradigm for PGCLC expansion, our system reconstitutes the epigenetic \"blank slate\" of the germ line, an immediate precursory state for sexually dimorphic differentiation.", "classifications": [ { "id": "Yamamoto", "label": "Group Yamamoto", "parent": "Toyoshima", "type": "group" }, { "id": "Toyoshima", "label": "Team Toyoshima", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Ohta", "name": null }, { "creator_type": "author", "first_name": "Kazuki", "last_name": "Kurimoto", "name": null }, { "creator_type": "author", "first_name": "Ikuhiro", "last_name": "Okamoto", "name": null }, { "creator_type": "author", "first_name": "Tomonori", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Yukihiro", "last_name": "Yabuta", "name": null }, { "creator_type": "author", "first_name": "Hidetaka", "last_name": "Miyauchi", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Yukiko", "last_name": "Okuno", "name": null }, { "creator_type": "author", "first_name": "Masatoshi", "last_name": "Hagiwara", "name": null }, { "creator_type": "author", "first_name": "Kenjiro", "last_name": "Shirane", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Sasaki", "name": null }, { "creator_type": "author", "first_name": "Mitinori", "last_name": "Saitou", "name": null } ], "identifiers": { "doi": { "normalized": "10.15252/embj.201695862" }, "pmcid": { "normalized": "PMC5494472" }, "pmid": { "normalized": "28559416" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": true }, { "descriptor": "Cell Proliferation", "descriptor_ui": "D049109", "major_topic": true }, { "descriptor": "Colforsin", "descriptor_ui": "D005576", "major_topic": false }, { "descriptor": "Embryonic Stem Cells", "descriptor_ui": "D053595", "major_topic": false }, { "descriptor": "Epigenesis, Genetic", "descriptor_ui": "D044127", "major_topic": true }, { "descriptor": "Germ Cells", "descriptor_ui": "D005854", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Rolipram", "descriptor_ui": "D020889", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Jul 3", "date_precision": "day", "issue": "13", "normalized_date": "2017-07-03", "pages": "1888-1907", "proceedings_title": null, "publisher": "", "title": "The EMBO journal", "volume": "36", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "In vitro expansion of mouse primordial germ cell-like cells recapitulates an epigenetic blank slate.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Elena Yukie", "last_name": "Yoshitoshi-Uebayashi", "name": null }, { "creator_type": "author", "first_name": "Taro", "last_name": "Toyoda", "name": null }, { "creator_type": "author", "first_name": "Katsutaro", "last_name": "Yasuda", "name": null }, { "creator_type": "author", "first_name": "Maki", "last_name": "Kotaka", "name": null }, { "creator_type": "author", "first_name": "Keiko", "last_name": "Nomoto", "name": null }, { "creator_type": "author", "first_name": "Keisuke", "last_name": "Okita", "name": null }, { "creator_type": "author", "first_name": "Kentaro", "last_name": "Yasuchika", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Okamoto", "name": null }, { "creator_type": "author", "first_name": "Noriyuki", "last_name": "Takubo", "name": null }, { "creator_type": "author", "first_name": "Toshiya", "last_name": "Nishikubo", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Shinji", "last_name": "Uemoto", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Osafune", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.bbrc.2017.05.055" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "28528898" } }, "mesh": [], "publication": { "conference_name": null, "date": "2017 Jul 1", "date_precision": "day", "issue": "3", "normalized_date": "2017-07-01", "pages": "570-571", "proceedings_title": null, "publisher": "", "title": "Biochemical and biophysical research communications", "volume": "488", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Corrigendum to \"Modelling urea-cycle disorder citrullinemia type 1 with disease-specific iPSCs\" [Biochem. Biophys. Res. Commun. 486(3) (2017) 613-619].", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Intracellular fluorescence lifetime and intensity images of the endogenous fluorophore of nicotinamide adenine dinucleotide (NADH) have been observed before and after application of nanosecond pulsed electric field (nsPEF) in normal and cancer cells, that is, in Wistar-King-Aptekman rat fetus fibroblast (WFB) cells and W31 cells, which are the malignant transformed cells from WFB. The application of nsPEF induces a change both in intensity and lifetime of NADH, indicating that the intracellular function is affected by application of nsPEF in both normal and cancer cells. The application of nsPEF induces an increase in the fluorescence lifetime of NADH and a morphological change, which is attributed to the induction of apoptosis by nsPEF. The field effect on the intensity and lifetime clearly depends on the pulse width, and magnitude of the field-induced increase in the fluorescence lifetime of NADH has a tendency to increase with a decreasing pulse width. It is also found that apoptosis can be induced only in cancer cells using a suitable nsPEF, showing a possibility that ultrashort pulsed electric field is applicable for drug-free cancer therapy.", "classifications": [ { "id": "Nakabayashi", "label": "Group Nakabayashi", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Kamlesh", "last_name": "Awasthi", "name": null }, { "creator_type": "author", "first_name": "Takakazu", "last_name": "Nakabayashi", "name": null }, { "creator_type": "author", "first_name": "Liming", "last_name": "Li", "name": null }, { "creator_type": "author", "first_name": "Nobuhiro", "last_name": "Ohta", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/acsomega.7b00315" }, "pmcid": { "normalized": "PMC6044780" }, "pmid": { "normalized": "30023680" } }, "mesh": [], "publication": { "conference_name": null, "date": "2017 Jun 30", "date_precision": "day", "issue": "6", "normalized_date": "2017-06-30", "pages": "2916-2924", "proceedings_title": null, "publisher": "", "title": "ACS omega", "volume": "2", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Effects of Nanosecond Pulsed Electric Field on Intracellular NADH Autofluorescence: A Comparison between Normal and Cancer Cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "An enantioselective [3 + 2] cycloaddition reaction between nitrile oxides and transiently generated enolates of α-keto esters has been developed. The catalyst system was found to be compatible with in situ nitrile oxidegeneration conditions. A versatile array of nitrile oxides and α-keto esters could participate in the cycloaddition, providing novel 5-hydroxy-2-isoxazolines in high chemical yield with high levels of diastereo- and enantioselectivity. Notably, the optimal reaction conditions circumvented concurrent reactions via Oimidoylation and hetero-[3 + 2] pathways.", "classifications": [ { "id": "Sodeoka", "label": "Group Sodeoka", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Samuel L.", "last_name": "Bartlett", "name": null }, { "creator_type": "author", "first_name": "Yoshihiro", "last_name": "Sohtome", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Hashizume", "name": null }, { "creator_type": "author", "first_name": "Peter S.", "last_name": "White", "name": null }, { "creator_type": "author", "first_name": "Miki", "last_name": "Sawamura", "name": null }, { "creator_type": "author", "first_name": "Jeffrey S.", "last_name": "Johnson", "name": null }, { "creator_type": "author", "first_name": "Mikiko", "last_name": "Sodeoka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/jacs.7b03782" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "28581747" } }, "mesh": [ { "descriptor": "Alcohols", "descriptor_ui": "D000438", "major_topic": false }, { "descriptor": "Catalysis", "descriptor_ui": "D002384", "major_topic": false }, { "descriptor": "Cycloaddition Reaction", "descriptor_ui": "D061565", "major_topic": false }, { "descriptor": "Esters", "descriptor_ui": "D004952", "major_topic": false }, { "descriptor": "Ketones", "descriptor_ui": "D007659", "major_topic": false }, { "descriptor": "Molecular Structure", "descriptor_ui": "D015394", "major_topic": false }, { "descriptor": "Nitriles", "descriptor_ui": "D009570", "major_topic": false }, { "descriptor": "Oxides", "descriptor_ui": "D010087", "major_topic": false }, { "descriptor": "Stereoisomerism", "descriptor_ui": "D013237", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Jun 28", "date_precision": "day", "issue": "25", "normalized_date": "2017-06-28", "pages": "8661-8666", "proceedings_title": null, "publisher": "", "title": "Journal of the American Chemical Society", "volume": "139", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Catalytic Enantioselective [3 + 2] Cycloaddition of α–Keto Ester Enolates and Nitrile Oxides.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Subcellular resolution imaging of the whole brain and subsequent image analysis are prerequisites for understanding anatomical and functional brain networks. Here, we have developed a very high-speed serial-sectioning imaging system named FAST (block-face serial microscopy tomography), which acquires high-resolution images of a whole mouse brain in a speed range comparable to that of light-sheet fluorescence microscopy. FAST enables complete visualization of the brain at a resolution sufficient to resolve all cells and their subcellular structures. FAST renders unbiased quantitative group comparisons of normal and disease model brain cells for the whole brain at a high spatial resolution. Furthermore, FAST is highly scalable to non-human primate brains and human postmortem brain tissues, and can visualize neuronal projections in a whole adult marmoset brain. Thus, FAST provides new opportunities for global approaches that will allow for a better understanding of brain systems in multiple animal models and in human diseases.", "classifications": [ { "id": "Fujita", "label": "Group Fujita", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "contributor", "first_name": "Kaoru", "last_name": "Seiriki", "name": null }, { "creator_type": "contributor", "first_name": "Atsushi", "last_name": "Kasai", "name": null }, { "creator_type": "contributor", "first_name": "Takeshi", "last_name": "Hashimoto", "name": null }, { "creator_type": "contributor", "first_name": "Wiebke", "last_name": "Schulze", "name": null }, { "creator_type": "contributor", "first_name": "Misaki", "last_name": "Niu", "name": null }, { "creator_type": "contributor", "first_name": "Shun", "last_name": "Yamaguchi", "name": null }, { "creator_type": "contributor", "first_name": "Takanobu", "last_name": "Nakazawa", "name": null }, { "creator_type": "contributor", "first_name": "Ken-Ichi", "last_name": "Inoue", "name": null }, { "creator_type": "contributor", "first_name": "Shiori", "last_name": "Uezono", "name": null }, { "creator_type": "contributor", "first_name": "Masahiko", "last_name": "Takada", "name": null }, { "creator_type": "contributor", "first_name": "Yuichiro", "last_name": "Naka", "name": null }, { "creator_type": "contributor", "first_name": "Hisato", "last_name": "Igarashi", "name": null }, { "creator_type": "contributor", "first_name": "Masato", "last_name": "Tanuma", "name": null }, { "creator_type": "contributor", "first_name": "James A.", "last_name": "Waschek", "name": null }, { "creator_type": "contributor", "first_name": "Yukio", "last_name": "Ago", "name": null }, { "creator_type": "contributor", "first_name": "Kenji F.", "last_name": "Tanaka", "name": null }, { "creator_type": "contributor", "first_name": "Atsuko", "last_name": "Hayata-Takano", "name": null }, { "creator_type": "contributor", "first_name": "Kazuki", "last_name": "Nagayasu", "name": null }, { "creator_type": "contributor", "first_name": "Norihito", "last_name": "Shintani", "name": null }, { "creator_type": "contributor", "first_name": "Ryota", "last_name": "Hashimoto", "name": null }, { "creator_type": "contributor", "first_name": "Yasuto", "last_name": "Kunii", "name": null }, { "creator_type": "contributor", "first_name": "Mizuki", "last_name": "Hino", "name": null }, { "creator_type": "contributor", "first_name": "Junya", "last_name": "Matsumoto", "name": null }, { "creator_type": "contributor", "first_name": "Hirooki", "last_name": "Yabe", "name": null }, { "creator_type": "contributor", "first_name": "Takeharu", "last_name": "Nagai", "name": null }, { "creator_type": "contributor", "first_name": "Katsumasa", "last_name": "Fujita", "name": null }, { "creator_type": "contributor", "first_name": "Toshio", "last_name": "Matsuda", "name": null }, { "creator_type": "contributor", "first_name": "Kazuhiro", "last_name": "Takuma", "name": null }, { "creator_type": "contributor", "first_name": "Akemichi", "last_name": "Baba", "name": null }, { "creator_type": "contributor", "first_name": "Hitoshi", "last_name": "Hashimoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.neuron.2017.05.017" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "28641108" } }, "mesh": [ { "descriptor": "Aged, 80 and over", "descriptor_ui": "D000369", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Brain", "descriptor_ui": "D001921", "major_topic": false }, { "descriptor": "Callithrix", "descriptor_ui": "D002144", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Image Processing, Computer-Assisted", "descriptor_ui": "D007091", "major_topic": false }, { "descriptor": "Imaging, Three-Dimensional", "descriptor_ui": "D021621", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Microscopy", "descriptor_ui": "D008853", "major_topic": false }, { "descriptor": "Microscopy, Fluorescence", "descriptor_ui": "D008856", "major_topic": false }, { "descriptor": "Neurites", "descriptor_ui": "D016501", "major_topic": false }, { "descriptor": "Neuroimaging", "descriptor_ui": "D059906", "major_topic": false }, { "descriptor": "Tomography", "descriptor_ui": "D014054", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Jun 21", "date_precision": "day", "issue": "6", "normalized_date": "2017-06-21", "pages": "1085-1100.e6", "proceedings_title": null, "publisher": "", "title": "Neuron", "volume": "94", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "High-Speed and Scalable Whole-Brain Imaging in Rodents and Primates.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The histone methyltransferase EZH2, a key epigenetic modifier, is known to be associated with human tumorigenesis. However, the physiological importance of EZH2 and its clinical relevance in endometrial cancer remain unclear. Hence, in the present study, we investigated the expression and function of EZH2 in endometrial cancer. In a quantitative real-time PCR analysis of 11 endometrial cancer cell lines and 52 clinical endometrial cancer specimens, EZH2 was significantly overexpressed in cancer cells and tissues compared to that in corresponding normal control cells and tissues. Kaplan-Meier survival analysis using data of the TCGA RNA-seq database and tissue microarrays (TMAs) indicated that EZH2 overexpression is associated with endometrial cancer prognosis. In addition, knockdown of EZH2 using specific siRNAs resulted in growth suppression and apoptosis induction of endometrial cancer cells, accompanied by attenuation of H3K27 trimethylation. Consistent with these results, treatment with GSK126, a specific EZH2 inhibitor, suppressed endometrial cancer cell growth and decreased the number of cancer cell colonies. Furthermore, GSK126 showed additive effects with doxorubicin or cisplatin, which are conventional drugs for treatment of endometrial cancer. Further studies should explore the therapeutic potential of inhibiting EZH2 in patients with endometrial cancer.", "classifications": [ { "id": "Hamamoto", "label": "Group Hamamoto", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Shinya", "last_name": "Oki", "name": null }, { "creator_type": "author", "first_name": "Kenbun", "last_name": "Sone", "name": null }, { "creator_type": "author", "first_name": "Katsutoshi", "last_name": "Oda", "name": null }, { "creator_type": "author", "first_name": "Ryuji", "last_name": "Hamamoto", "name": null }, { "creator_type": "author", "first_name": "Masako", "last_name": "Ikemura", "name": null }, { "creator_type": "author", "first_name": "Daichi", "last_name": "Maeda", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Takeuchi", "name": null }, { "creator_type": "author", "first_name": "Michihiro", "last_name": "Tanikawa", "name": null }, { "creator_type": "author", "first_name": "Mayuyo", "last_name": "Mori-Uchino", "name": null }, { "creator_type": "author", "first_name": "Kazunori", "last_name": "Nagasaka", "name": null }, { "creator_type": "author", "first_name": "Aki", "last_name": "Miyasaka", "name": null }, { "creator_type": "author", "first_name": "Tomoko", "last_name": "Kashiyama", "name": null }, { "creator_type": "author", "first_name": "Yuji", "last_name": "Ikeda", "name": null }, { "creator_type": "author", "first_name": "Takahide", "last_name": "Arimoto", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Kuramoto", "name": null }, { "creator_type": "author", "first_name": "Osamu", "last_name": "Wada-Hiraike", "name": null }, { "creator_type": "author", "first_name": "Kei", "last_name": "Kawana", "name": null }, { "creator_type": "author", "first_name": "Masashi", "last_name": "Fukayama", "name": null }, { "creator_type": "author", "first_name": "Yutaka", "last_name": "Osuga", "name": null }, { "creator_type": "author", "first_name": "Tomoyuki", "last_name": "Fujii", "name": null } ], "identifiers": { "doi": { "normalized": "10.18632/oncotarget.16316" }, "pmcid": { "normalized": "PMC5522273" }, "pmid": { "normalized": "28418882" } }, "mesh": [ { "descriptor": "Antineoplastic Agents", "descriptor_ui": "D000970", "major_topic": false }, { "descriptor": "Antineoplastic Combined Chemotherapy Protocols", "descriptor_ui": "D000971", "major_topic": false }, { "descriptor": "Apoptosis", "descriptor_ui": "D017209", "major_topic": false }, { "descriptor": "Biomarkers, Tumor", "descriptor_ui": "D014408", "major_topic": false }, { "descriptor": "Carcinogenesis", "descriptor_ui": "D063646", "major_topic": false }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Cell Proliferation", "descriptor_ui": "D049109", "major_topic": false }, { "descriptor": "Cisplatin", "descriptor_ui": "D002945", "major_topic": false }, { "descriptor": "Doxorubicin", "descriptor_ui": "D004317", "major_topic": false }, { "descriptor": "Endometrial Neoplasms", "descriptor_ui": "D016889", "major_topic": false }, { "descriptor": "Enhancer of Zeste Homolog 2 Protein", "descriptor_ui": "D000071221", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Genetic Markers", "descriptor_ui": "D005819", "major_topic": false }, { "descriptor": "Histones", "descriptor_ui": "D006657", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Indoles", "descriptor_ui": "D007211", "major_topic": false }, { "descriptor": "Prognosis", "descriptor_ui": "D011379", "major_topic": false }, { "descriptor": "Pyridones", "descriptor_ui": "D011728", "major_topic": false }, { "descriptor": "RNA Interference", "descriptor_ui": "D034622", "major_topic": false }, { "descriptor": "RNA, Small Interfering", "descriptor_ui": "D034741", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Jun 20", "date_precision": "day", "issue": "25", "normalized_date": "2017-06-20", "pages": "40402-40411", "proceedings_title": null, "publisher": "", "title": "Oncotarget", "volume": "8", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Oncogenic histone methyltransferase EZH2: A novel prognostic marker with therapeutic potential in endometrial cancer.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: A germline deletion in the BIM (BCL2L11) gene has been shown to impair the apoptotic response to tyrosine kinase inhibitors (TKIs) in vitro but its association with poor outcomes in TKI-treated non-small cell lung cancer (NSCLC) patients remains unclear. We conducted a systematic review and meta-analysis on both aggregate and individual patient data to address this issue. RESULTS: In an aggregate data meta-analysis (n = 1429), the BIM deletion was associated with inferior PFS (HR = 1.51, 95%CI = 1.06-2.13, P = 0.02). Using individual patient data (n = 1200), we found a significant interaction between the deletion and ethnicity. Amongst non-Koreans, the deletion was an independent predictor of shorter PFS (Chinese: HR = 1.607, 95%CI = 1.251-2.065, P = 0.0002; Japanese: HR = 2.636, 95%CI = 1.603-4.335, P = 0.0001), and OS (HR = 1.457, 95% CI = 1.063-1.997, P = 0.019). In Kaplan-Meier analyses, the BIM deletion was associated with shorter survival in non-Koreans (PFS: 8.0 months v 11.1 months, P < 0.0005; OS: 25.7 v 30.0 months, P = 0.042). In Koreans, the BIM deletion was not predictive of PFS or OS. MATERIALS AND METHODS: 10 published and 3 unpublished studies that reported survival outcomes in NSCLC patients stratified according to BIM deletion were identified from PubMed and Embase. Summary risk estimates were calculated from aggregate patient data using a random-effects model. For individual patient data, Kaplan-Meier analyses were supported by multivariate Cox regression to estimate hazard ratios (HRs) for PFS and OS. CONCLUSIONS: In selected populations, the BIM deletion is a significant predictor of shorter PFS and OS on EGFR-TKIs. Further studies to determine its effect on response to other BIM-dependent therapeutic agents are needed, so that alternative treatment strategies may be devised.", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Sheila X.", "last_name": "Soh", "name": null }, { "creator_type": "author", "first_name": "Fahad J.", "last_name": "Siddiqui", "name": null }, { "creator_type": "author", "first_name": "John C.", "last_name": "Allen", "name": null }, { "creator_type": "author", "first_name": "Go Woon", "last_name": "Kim", "name": null }, { "creator_type": "author", "first_name": "Jae Cheol", "last_name": "Lee", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null }, { "creator_type": "author", "first_name": "Manabu", "last_name": "Soda", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Mano", "name": null }, { "creator_type": "author", "first_name": "Ross A.", "last_name": "Soo", "name": null }, { "creator_type": "author", "first_name": "Tan-Min", "last_name": "Chin", "name": null }, { "creator_type": "author", "first_name": "Hiromichi", "last_name": "Ebi", "name": null }, { "creator_type": "author", "first_name": "Seiji", "last_name": "Yano", "name": null }, { "creator_type": "author", "first_name": "Keitaro", "last_name": "Matsuo", "name": null }, { "creator_type": "author", "first_name": "Xiaomin", "last_name": "Niu", "name": null }, { "creator_type": "author", "first_name": "Shun", "last_name": "Lu", "name": null }, { "creator_type": "author", "first_name": "Kazutoshi", "last_name": "Isobe", "name": null }, { "creator_type": "author", "first_name": "Jih-Hsiang", "last_name": "Lee", "name": null }, { "creator_type": "author", "first_name": "James C.", "last_name": "Yang", "name": null }, { "creator_type": "author", "first_name": "Mingchuan", "last_name": "Zhao", "name": null }, { "creator_type": "author", "first_name": "Caicun", "last_name": "Zhou", "name": null }, { "creator_type": "author", "first_name": "June-Koo", "last_name": "Lee", "name": null }, { "creator_type": "author", "first_name": "Se-Hoon", "last_name": "Lee", "name": null }, { "creator_type": "author", "first_name": "Ji Yun", "last_name": "Lee", "name": null }, { "creator_type": "author", "first_name": "Myung-Ju", "last_name": "Ahn", "name": null }, { "creator_type": "author", "first_name": "Tira J.", "last_name": "Tan", "name": null }, { "creator_type": "author", "first_name": "Daniel S.", "last_name": "Tan", "name": null }, { "creator_type": "author", "first_name": "Eng-Huat", "last_name": "Tan", "name": null }, { "creator_type": "author", "first_name": "S. Tiong", "last_name": "Ong", "name": null }, { "creator_type": "author", "first_name": "Wan-Teck", "last_name": "Lim", "name": null } ], "identifiers": { "doi": { "normalized": "10.18632/oncotarget.17102" }, "pmcid": { "normalized": "PMC5522319" }, "pmid": { "normalized": "28467813" } }, "mesh": [ { "descriptor": "Bcl-2-Like Protein 11", "descriptor_ui": "D000072224", "major_topic": false }, { "descriptor": "Disease-Free Survival", "descriptor_ui": "D018572", "major_topic": false }, { "descriptor": "ErbB Receptors", "descriptor_ui": "D066246", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Lung Neoplasms", "descriptor_ui": "D008175", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": false }, { "descriptor": "Polymorphism, Genetic", "descriptor_ui": "D011110", "major_topic": false }, { "descriptor": "Treatment Outcome", "descriptor_ui": "D016896", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Jun 20", "date_precision": "day", "issue": "25", "normalized_date": "2017-06-20", "pages": "41474-41486", "proceedings_title": null, "publisher": "", "title": "Oncotarget", "volume": "8", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "A systematic review and meta-analysis of individual patient data on the impact of the BIM deletion polymorphism on treatment outcomes in epidermal growth factor receptor mutant lung cancer.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: Recent advances in bioimaging and automated analysis methods have enabled the large-scale systematic analysis of cellular dynamics during the embryonic development of Caenorhabditis elegans. Most of these analyses have focused on cell lineage tracing rather than cell shape dynamics. Cell shape analysis requires cell membrane segmentation, which is challenging because of insufficient resolution and image quality. This problem is currently solved by complicated segmentation methods requiring laborious and time consuming parameter adjustments. RESULTS: Our new framework BCOMS (Biologically Constrained Optimization based cell Membrane Segmentation) automates the extraction of the cell shape of C. elegans embryos. Both the segmentation and evaluation processes are automated. To automate the evaluation, we solve an optimization problem under biological constraints. The performance of BCOMS was validated against a manually created ground truth of the 24-cell stage embryo. The average deviation of 25 cell shape features was 5.6%. The deviation was mainly caused by membranes parallel to the focal planes, which either contact the surfaces of adjacent cells or make no contact with other cells. Because segmentation of these membranes was difficult even by manual inspection, the automated segmentation was sufficiently accurate for cell shape analysis. As the number of manually created ground truths is necessarily limited, we compared the segmentation results between two adjacent time points. Across all cells and all cell cycles, the average deviation of the 25 cell shape features was 4.3%, smaller than that between the automated segmentation result and ground truth. CONCLUSIONS: BCOMS automated the accurate extraction of cell shapes in developing C. elegans embryos. By replacing image processing parameters with easily adjustable biological constraints, BCOMS provides a user-friendly framework. The framework is also applicable to other model organisms. Creating the biological constraints is a critical step requiring collaboration between an experimentalist and a software developer.", "classifications": [ { "id": "Onami", "label": "Group Onami", "parent": "Fujiwara", "type": "group" }, { "id": "Fujiwara", "label": "Team Fujiwara", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yusuke", "last_name": "Azuma", "name": null }, { "creator_type": "author", "first_name": "Shuichi", "last_name": "Onami", "name": null } ], "identifiers": { "doi": { "normalized": "10.1186/s12859-017-1717-6" }, "pmcid": { "normalized": "PMC5477254" }, "pmid": { "normalized": "28629355" } }, "mesh": [ { "descriptor": "Algorithms", "descriptor_ui": "D000465", "major_topic": true }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Automation", "descriptor_ui": "D001331", "major_topic": false }, { "descriptor": "Caenorhabditis elegans", "descriptor_ui": "D017173", "major_topic": false }, { "descriptor": "Cell Membrane", "descriptor_ui": "D002462", "major_topic": false }, { "descriptor": "Embryo, Nonmammalian", "descriptor_ui": "D004625", "major_topic": false }, { "descriptor": "Embryonic Development", "descriptor_ui": "D047108", "major_topic": false }, { "descriptor": "Image Processing, Computer-Assisted", "descriptor_ui": "D007091", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Jun 19", "date_precision": "day", "issue": "1", "normalized_date": "2017-06-19", "pages": "307", "proceedings_title": null, "publisher": "", "title": "BMC bioinformatics", "volume": "18", "year": 2017 }, "ssbd": { "database": [ "ssbd-database-000020" ], "repository": [ "ssbd-repos-000020" ] }, "title": "Biologically constrained optimization based cell membrane segmentation in C. elegans embryos.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: Breast adipocytes play important roles in both the development and function of mammary epithelial cells. Therefore, carcinoma-adipose stromal cell (ASC) interactions have been considered pivotal in supporting tumor growth in breast cancer. In addition, it has been demonstrated that the biological features of cancer-associated adipocytes differ from those of normal ASCs. Therefore, we investigated an interaction between ASCs and carcinoma cell lines to identify genes associated with ASC invasion of carcinoma cells. METHODS: 3T3-L1 ASC-derived conditioned medium (CM) was treated to measure the proliferation rate of breast cancer cells. To further examine the effect of ASCs, breast cancer cells were cocultivated with either primary human or 3T3-L1 ASCs for migration assays, DNA microarrays, quantitative real-time polymerase chain reactions, and Western blotting experiments. Furthermore, immunoreactivity of S100A7, the most upregulated gene in MCF7, after coculture with ASCs was evaluated for 150 breast cancer tissues to statistically analyze its association with clinicopathological parameters. RESULTS: We first confirmed that ASC-derived CM treatment enhanced the cell proliferation rate of MCF7, T47D, SK-BR-3, and ZR-75-1 cell lines, whereas the migration rate of breast cancer cells was promoted by coculture with ASCs. We identified that a small calcium-binding protein, S100A7, was markedly upregulated (by 5.8-fold) in MCF7 cells after coculture with primary human ASCs. Knockdown of S100A7 significantly suppressed ASC-stimulated cell proliferation and migration rate, indicating a possible involvement of S100A7 in the carcinoma-ASC interaction in breast tumors. Furthermore, strong S100A7 immunoreactivity was detected at the invasive front of adipose stromal tissues compared with that at the intratumoral area. The status of S100A7 was also significantly correlated with adverse pathological parameters, and multivariate analysis revealed that S100A7 could be an independent prognostic marker for a poor relapse-free survival rate. Moreover, induction of oncostatin M was detected in cancer-stimulated ASCs, whereas the downstream S100A7 binding proteins/receptor for advanced glycation endproducts were significantly upregulated in correspondence with S100A7 expression in breast cancer cells after coculture with ASCs. CONCLUSIONS: The results of our study suggest that paracrine production of cytokines from ASCs stimulates breast carcinoma cell growth via upregulation of S100A7 expression in breast cancer cell lines.", "classifications": [ { "id": "Suzuki", "label": "Group Suzuki", "parent": "Takekawa", "type": "group" }, { "id": "Takekawa", "label": "Team Takekawa", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Minako", "last_name": "Sakurai", "name": null }, { "creator_type": "author", "first_name": "Yasuhiro", "last_name": "Miki", "name": null }, { "creator_type": "author", "first_name": "Kiyoshi", "last_name": "Takagi", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Takanori", "last_name": "Ishida", "name": null }, { "creator_type": "author", "first_name": "Noriaki", "last_name": "Ohuchi", "name": null }, { "creator_type": "author", "first_name": "Hironobu", "last_name": "Sasano", "name": null } ], "identifiers": { "doi": { "normalized": "10.1186/s13058-017-0863-0" }, "pmcid": { "normalized": "PMC5477117" }, "pmid": { "normalized": "28629450" } }, "mesh": [ { "descriptor": "3T3-L1 Cells", "descriptor_ui": "D041721", "major_topic": false }, { "descriptor": "Adipocytes", "descriptor_ui": "D017667", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Breast Neoplasms", "descriptor_ui": "D001943", "major_topic": false }, { "descriptor": "Cancer-Associated Fibroblasts", "descriptor_ui": "D000072645", "major_topic": false }, { "descriptor": "Cell Communication", "descriptor_ui": "D002450", "major_topic": true }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Cell Movement", "descriptor_ui": "D002465", "major_topic": false }, { "descriptor": "Cell Proliferation", "descriptor_ui": "D049109", "major_topic": false }, { "descriptor": "Culture Media, Conditioned", "descriptor_ui": "D017077", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Gene Expression Regulation, Neoplastic", "descriptor_ui": "D015972", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Immunohistochemistry", "descriptor_ui": "D007150", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Neoplasm Grading", "descriptor_ui": "D060787", "major_topic": false }, { "descriptor": "Neoplasm Metastasis", "descriptor_ui": "D009362", "major_topic": false }, { "descriptor": "Neoplasm Staging", "descriptor_ui": "D009367", "major_topic": false }, { "descriptor": "Prognosis", "descriptor_ui": "D011379", "major_topic": false }, { "descriptor": "S100 Calcium Binding Protein A7", "descriptor_ui": "D000075023", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Stromal Cells", "descriptor_ui": "D017154", "major_topic": false }, { "descriptor": "Tumor Microenvironment", "descriptor_ui": "D059016", "major_topic": true } ], "publication": { "conference_name": null, "date": "2017 Jun 19", "date_precision": "day", "issue": "1", "normalized_date": "2017-06-19", "pages": "70", "proceedings_title": null, "publisher": "", "title": "Breast cancer research : BCR", "volume": "19", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Interaction with adipocyte stromal cells induces breast cancer malignancy via S100A7 upregulation in breast cancer microenvironment.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Stereoselective synthesis of the ent-ZA'B'C'D'-ring system of maitotoxin has been accomplished through a convergent strategy utilizing Suzuki-Miyaura cross coupling reaction of ZA'-ring alkylborane and C'D'-ring (Z)-vinyl iodide, and subsequent construction of the B'-ring by reduction of the O,S-acetal.", "classifications": [ { "id": "Sodeoka", "label": "Group Sodeoka", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Tatsuo", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Masayuki", "last_name": "Morita", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Koshino", "name": null }, { "creator_type": "author", "first_name": "Mikiko", "last_name": "Sodeoka", "name": null }, { "creator_type": "author", "first_name": "Tadashi", "last_name": "Nakata", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/acs.orglett.7b01301" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "28571323" } }, "mesh": [ { "descriptor": "Marine Toxins", "descriptor_ui": "D008387", "major_topic": false }, { "descriptor": "Molecular Structure", "descriptor_ui": "D015394", "major_topic": false }, { "descriptor": "Oxocins", "descriptor_ui": "D035964", "major_topic": false }, { "descriptor": "Polyether Toxins", "descriptor_ui": "D000095702", "major_topic": false }, { "descriptor": "Stereoisomerism", "descriptor_ui": "D013237", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Jun 16", "date_precision": "day", "issue": "12", "normalized_date": "2017-06-16", "pages": "3203-3206", "proceedings_title": null, "publisher": "", "title": "Organic letters", "volume": "19", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Convergent Synthesis of the ent-ZA'B'C'D'-Ring System of Maitotoxin.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Temporal focusing (TF) microscopy is a wide-field two-photon excitation fluorescence (2PEF) microscopy technique, the optical sectioning capability of which is lower than that of point-scanning 2PEF microscopy. Here we demonstrate TF microscopy using three-photon excitation fluorescence (3PEF), which enhances the optical sectioning capability. As an excitation light source for the 3PEF, we developed an Yb-fiber chirped pulse amplifier, which produces 92-fs 9.0-muJ 1060-nm pulses at a repetition rate of 200 kHz. The optical sectioning capability was improved by a factor of 1.3 compared with that of 2PEF-TF microscopy. We also demonstrate dual-color imaging with both 2PEF and 3PEF.", "classifications": [ { "id": "Isobe", "label": "Group Isobe", "parent": "Imayoshi", "type": "group" }, { "id": "Imayoshi", "label": "Team Imayoshi", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Keisuke", "last_name": "Toda", "name": null }, { "creator_type": "author", "first_name": "Keisuke", "last_name": "Isobe", "name": null }, { "creator_type": "author", "first_name": "Kana", "last_name": "Namiki", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Kawano", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Miyawaki", "name": null }, { "creator_type": "author", "first_name": "Katsumi", "last_name": "Midorikawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1364/boe.8.002796" }, "pmcid": { "normalized": "PMC5480430" }, "pmid": { "normalized": "28663907" } }, "mesh": [], "publication": { "conference_name": null, "date": "2017 Jun 1", "date_precision": "day", "issue": "6", "normalized_date": "2017-06-01", "pages": "2796-2806", "proceedings_title": null, "publisher": "", "title": "Biomedical optics express", "volume": "8", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Temporal focusing microscopy using three-photon excitation fluorescence with a 92-fs Yb-fiber chirped pulse amplifier.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The mechanisms for human germ cell development have remained largely unknown, due to the difficulty in obtaining suitable experimental materials. The establishment of an in vitro system to reconstitute human germ cell development will thus provide a critical opportunity to understand its mechanisms at a molecular level. It has previously been shown that human induced pluripotent stem cells (hiPSCs) are first induced into incipient mesoderm-like cells (iMeLCs), which are in turn induced into primordial germ-cell like cells (PGCLCs) with gene expression properties similar to early migratory PGCs. Here, we report that the efficiency of PGCLC induction varies among hiPSC clones, and, interestingly, the clonal variations in PGCLC induction efficiency are reflected in the gene expression states of the iMeLCs. Remarkably, the expression levels of EOMES, MIXL1, or T in the iMeLCs are positively correlated with the efficiency of subsequent PGCLC generation, while the expressions of CDH1, SOX3, or FGF2 are negatively correlated. These results indicate that the expression changes of these genes occurring during iMeLC induction are key markers indicative of successful induction of PGCLCs, and furthermore, that hiPSC clones have different properties that influence their responsivity to the iMeLC induction. Our study thus provides important insights into the mechanism of hPGC specification as well as the development of a better strategy for inducing human germ cell fate from PSCs in vitro.", "classifications": [ { "id": "Yamamoto", "label": "Group Yamamoto", "parent": "Toyoshima", "type": "group" }, { "id": "Toyoshima", "label": "Team Toyoshima", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Shihori", "last_name": "Yokobayashi", "name": null }, { "creator_type": "author", "first_name": "Keisuke", "last_name": "Okita", "name": null }, { "creator_type": "author", "first_name": "Masato", "last_name": "Nakagawa", "name": null }, { "creator_type": "author", "first_name": "Tomonori", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Yukihiro", "last_name": "Yabuta", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Mitinori", "last_name": "Saitou", "name": null } ], "identifiers": { "doi": { "normalized": "10.1093/biolre/iox038" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "28453617" } }, "mesh": [ { "descriptor": "Antibodies", "descriptor_ui": "D000906", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Gene Expression Regulation", "descriptor_ui": "D005786", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Karyotype", "descriptor_ui": "D059785", "major_topic": false }, { "descriptor": "Pluripotent Stem Cells", "descriptor_ui": "D039904", "major_topic": false }, { "descriptor": "Sex Chromosomes", "descriptor_ui": "D012730", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Jun 1", "date_precision": "day", "issue": "6", "normalized_date": "2017-06-01", "pages": "1154-1166", "proceedings_title": null, "publisher": "", "title": "Biology of reproduction", "volume": "96", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Clonal variation of human induced pluripotent stem cells for induction into the germ cell fate.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The Kolliker-Fuse nucleus (KF) is known primarily for its respiratory function as the \"pneumotaxic center\" or \"pontine respiratory group.\" Considered part of the parabrachial (PB) complex, KF contains glutamatergic neurons that project to respiratory-related targets in the medulla and spinal cord (Yokota, Oka, Tsumori, Nakamura, & Yasui, 2007). Here we describe an unexpected population of neurons in the caudal KF and adjacent lateral crescent subnucleus (PBlc), which are gamma-aminobutyric acid (GABA)ergic and have an entirely different pattern of projections than glutamatergic KF neurons. First, immunofluorescence, in situ hybridization, and Cre-reporter labeling revealed that many of these GABAergic neurons express FoxP2 in both rats and mice. Next, using Cre-dependent axonal tracing in Vgat-IRES-Cre and Vglut2-IRES-Cre mice, we identified different projection patterns from GABAergic and glutamatergic neurons in this region. GABAergic neurons in KF and PBlc project heavily and almost exclusively to trigeminal sensory nuclei, with minimal projections to cardiorespiratory nuclei in the brainstem, and none to the spinal cord. In contrast, glutamatergic KF neurons project heavily to the autonomic, respiratory, and motor regions of the medulla and spinal cord previously identified as efferent targets mediating KF cardiorespiratory effects. These findings identify a novel, GABAergic subpopulation of KF/PB neurons with a distinct efferent projection pattern targeting the brainstem trigeminal sensory system. Rather than regulating breathing, we propose that these neurons influence vibrissal sensorimotor function.", "classifications": [ { "id": "Yokota", "label": "Group Yokota", "parent": "Enomoto", "type": "group" }, { "id": "Enomoto", "label": "Team Enomoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Joel C.", "last_name": "Geerling", "name": null }, { "creator_type": "author", "first_name": "Shigefumi", "last_name": "Yokota", "name": null }, { "creator_type": "author", "first_name": "Irma", "last_name": "Rukhadze", "name": null }, { "creator_type": "author", "first_name": "Dan", "last_name": "Roe", "name": null }, { "creator_type": "author", "first_name": "Nancy L.", "last_name": "Chamberlin", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/cne.24164" }, "pmcid": { "normalized": "PMC5832451" }, "pmid": { "normalized": "28032634" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Fluorescent Antibody Technique", "descriptor_ui": "D005455", "major_topic": false }, { "descriptor": "GABAergic Neurons", "descriptor_ui": "D059330", "major_topic": false }, { "descriptor": "Glutamic Acid", "descriptor_ui": "D018698", "major_topic": false }, { "descriptor": "Image Processing, Computer-Assisted", "descriptor_ui": "D007091", "major_topic": false }, { "descriptor": "Immunohistochemistry", "descriptor_ui": "D007150", "major_topic": false }, { "descriptor": "In Situ Hybridization", "descriptor_ui": "D017403", "major_topic": false }, { "descriptor": "Kolliker-Fuse Nucleus", "descriptor_ui": "D065836", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Transgenic", "descriptor_ui": "D008822", "major_topic": false }, { "descriptor": "Neural Pathways", "descriptor_ui": "D009434", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Rats, Wistar", "descriptor_ui": "D017208", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Jun 1", "date_precision": "day", "issue": "8", "normalized_date": "2017-06-01", "pages": "1844-1860", "proceedings_title": null, "publisher": "", "title": "The Journal of comparative neurology", "volume": "525", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Kolliker-Fuse GABAergic and glutamatergic neurons project to distinct targets.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Hydrogen sulfide (H(2)S) signaling involves polysulfide (RSS(n)SR') formation on various proteins. However, the current lack of sensitive polysulfide detection assays poses methodological challenges for understanding sulfane sulfur homeostasis and signaling. We developed a novel combined assay by modifying Sulfide Antioxidant Buffer (SAOB) to produce an \"Elimination Method of Sulfide from Polysulfide\" (EMSP) treatment solution that liberates sulfide, followed with methylene blue (MB) sulfide detection assay. The combined EMSP-MB sulfide detection assay performed on low molecular weight sulfur species showed that sulfide was produced from trisulfide compounds such as glutathione trisulfide and diallyl trisulfide, but not from the thiol compounds such as cysteine, cystine and glutathione. In the case of plasma proteins, this novel combined detection assay revealed that approximately 14.7, 1.7, 3.9, 3.7 sulfide mol/mol released from human serum albumin, alpha(1)-anti-trypsin, alpha(1)-acid glycoprotein and ovalbumin, respectively, suggesting that serum albumin is a major pool of polysulfide in human blood circulation. Taken together with the results of albumins of different species, the liberated sulfide has a good correlation with cysteine instead of methionine, indicating the site of incorporation of polysulfide is cysteine. With this novel sulfide detention assay, approximately 8,000, 120 and 1100 muM of polysulfide concentrations was quantitated in human healthy plasma, saliva and tear, respectively. Our promising polysulfide specific detection assay can be a very important tool because quantitative determination of polysulfide sheds light on the functional consequence of protein-bound cysteine polysulfide and expands the research area of reactive oxygen to reactive polysulfide species.", "classifications": [ { "id": "Akaike", "label": "Group Akaike", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Mayumi", "last_name": "Ikeda", "name": null }, { "creator_type": "author", "first_name": "Yu", "last_name": "Ishima", "name": null }, { "creator_type": "author", "first_name": "Akitomo", "last_name": "Shibata", "name": null }, { "creator_type": "author", "first_name": "Victor T. G.", "last_name": "Chuang", "name": null }, { "creator_type": "author", "first_name": "Tomohiro", "last_name": "Sawa", "name": null }, { "creator_type": "author", "first_name": "Hideshi", "last_name": "Ihara", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Ming", "last_name": "Xian", "name": null }, { "creator_type": "author", "first_name": "Yuya", "last_name": "Ouchi", "name": null }, { "creator_type": "author", "first_name": "Taro", "last_name": "Shimizu", "name": null }, { "creator_type": "author", "first_name": "Hidenori", "last_name": "Ando", "name": null }, { "creator_type": "author", "first_name": "Masami", "last_name": "Ukawa", "name": null }, { "creator_type": "author", "first_name": "Tatsuhiro", "last_name": "Ishida", "name": null }, { "creator_type": "author", "first_name": "Takaaki", "last_name": "Akaike", "name": null }, { "creator_type": "author", "first_name": "Masaki", "last_name": "Otagiri", "name": null }, { "creator_type": "author", "first_name": "Toru", "last_name": "Maruyama", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.aca.2017.03.027" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "28411626" } }, "mesh": [ { "descriptor": "Albumins", "descriptor_ui": "D000418", "major_topic": false }, { "descriptor": "Blood Proteins", "descriptor_ui": "D001798", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Hydrogen Sulfide", "descriptor_ui": "D006862", "major_topic": false }, { "descriptor": "Saliva", "descriptor_ui": "D012463", "major_topic": false }, { "descriptor": "Sulfides", "descriptor_ui": "D013440", "major_topic": false }, { "descriptor": "Sulfur", "descriptor_ui": "D013455", "major_topic": false }, { "descriptor": "Tears", "descriptor_ui": "D013666", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 May 29", "date_precision": "day", "issue": "", "normalized_date": "2017-05-29", "pages": "18-25", "proceedings_title": null, "publisher": "", "title": "Analytica chimica acta", "volume": "969", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Quantitative determination of polysulfide in albumins, plasma proteins and biological fluid samples using a novel combined assays approach.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Amyotrophic lateral sclerosis (ALS), a fatal disease causing progressive loss of motor neurons, still has no effective treatment. We developed a phenotypic screen to repurpose existing drugs using ALS motor neuron survival as readout. Motor neurons were generated from induced pluripotent stem cells (iPSCs) derived from an ALS patient with a mutation in superoxide dismutase 1 (SOD1). Results of the screen showed that more than half of the hits targeted the Src/c-Abl signaling pathway. Src/c-Abl inhibitors increased survival of ALS iPSC-derived motor neurons in vitro. Knockdown of Src or c-Abl with small interfering RNAs (siRNAs) also rescued ALS motor neuron degeneration. One of the hits, bosutinib, boosted autophagy, reduced the amount of misfolded mutant SOD1 protein, and attenuated altered expression of mitochondrial genes. Bosutinib also increased survival in vitro of ALS iPSC-derived motor neurons from patients with sporadic ALS or other forms of familial ALS caused by mutations in TAR DNA binding protein (TDP-43) or repeat expansions in C9orf72 Furthermore, bosutinib treatment modestly extended survival of a mouse model of ALS with an SOD1 mutation, suggesting that Src/c-Abl may be a potentially useful target for developing new drugs to treat ALS.", "classifications": [ { "id": "Yamamoto", "label": "Group Yamamoto", "parent": "Toyoshima", "type": "group" }, { "id": "Toyoshima", "label": "Team Toyoshima", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Keiko", "last_name": "Imamura", "name": null }, { "creator_type": "author", "first_name": "Yuishin", "last_name": "Izumi", "name": null }, { "creator_type": "author", "first_name": "Akira", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Kayoko", "last_name": "Tsukita", "name": null }, { "creator_type": "author", "first_name": "Knut", "last_name": "Woltjen", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Akitsu", "last_name": "Hotta", "name": null }, { "creator_type": "author", "first_name": "Takayuki", "last_name": "Kondo", "name": null }, { "creator_type": "author", "first_name": "Shiho", "last_name": "Kitaoka", "name": null }, { "creator_type": "author", "first_name": "Akira", "last_name": "Ohta", "name": null }, { "creator_type": "author", "first_name": "Akito", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Dai", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Mitsuya", "last_name": "Morita", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Takuma", "name": null }, { "creator_type": "author", "first_name": "Akira", "last_name": "Tamaoka", "name": null }, { "creator_type": "author", "first_name": "Tilo", "last_name": "Kunath", "name": null }, { "creator_type": "author", "first_name": "Selina", "last_name": "Wray", "name": null }, { "creator_type": "author", "first_name": "Hirokazu", "last_name": "Furuya", "name": null }, { "creator_type": "author", "first_name": "Takumi", "last_name": "Era", "name": null }, { "creator_type": "author", "first_name": "Kouki", "last_name": "Makioka", "name": null }, { "creator_type": "author", "first_name": "Koichi", "last_name": "Okamoto", "name": null }, { "creator_type": "author", "first_name": "Takao", "last_name": "Fujisawa", "name": null }, { "creator_type": "author", "first_name": "Hideki", "last_name": "Nishitoh", "name": null }, { "creator_type": "author", "first_name": "Kengo", "last_name": "Homma", "name": null }, { "creator_type": "author", "first_name": "Hidenori", "last_name": "Ichijo", "name": null }, { "creator_type": "author", "first_name": "Jean-Pierre", "last_name": "Julien", "name": null }, { "creator_type": "author", "first_name": "Nanako", "last_name": "Obata", "name": null }, { "creator_type": "author", "first_name": "Masato", "last_name": "Hosokawa", "name": null }, { "creator_type": "author", "first_name": "Haruhiko", "last_name": "Akiyama", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Kaneko", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Ayaki", "name": null }, { "creator_type": "author", "first_name": "Hidefumi", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Ryuji", "last_name": "Kaji", "name": null }, { "creator_type": "author", "first_name": "Ryosuke", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Yamanaka", "name": null }, { "creator_type": "author", "first_name": "Haruhisa", "last_name": "Inoue", "name": null } ], "identifiers": { "doi": { "normalized": "10.1126/scitranslmed.aaf3962" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "28539470" } }, "mesh": [ { "descriptor": "Amyotrophic Lateral Sclerosis", "descriptor_ui": "D000690", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Induced Pluripotent Stem Cells", "descriptor_ui": "D057026", "major_topic": false }, { "descriptor": "Motor Neurons", "descriptor_ui": "D009046", "major_topic": false }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": false }, { "descriptor": "Proto-Oncogene Proteins c-abl", "descriptor_ui": "D016315", "major_topic": false }, { "descriptor": "Proto-Oncogene Proteins pp60(c-src)", "descriptor_ui": "D016392", "major_topic": false }, { "descriptor": "Superoxide Dismutase", "descriptor_ui": "D013482", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 May 24", "date_precision": "day", "issue": "391", "normalized_date": "2017-05-24", "pages": "eaaf3962", "proceedings_title": null, "publisher": "", "title": "Science translational medicine", "volume": "9", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "The Src/c-Abl pathway is a potential therapeutic target in amyotrophic lateral sclerosis.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Coronatine (1), a small-molecular virulence factor produced by plant-pathogenic bacteria, promotes bacterial infection by inducing the opening of stomatal pores, the major route of bacterial entry into the plant, via the jasmonate-mediated COI1-JAZ signaling pathway. However, this pathway is also important for multiple plant functions, including defense against wounding by herbivorous insects. Thus, suppression of the COI1-JAZ signaling pathway to block bacterial infection would concomitantly impair plant defense against herbivorous wounding. Here, we report additional, COI1-JAZ-independent, action of 1 in Arabidopsis thaliana guard cells. First, we found that a stereoisomer of 1 regulates the movement of Arabidopsis guard cells without affecting COI1-JAZ signaling. Second, we found using alkyne-tagged Raman imaging (ATRI) that 1 is localized to the endoplasmic reticulum (ER) of living guard cells of Arabidopsis. The use of arc6 mutant lacking chloroplast formation was pivotal to circumvent the issue of autofluorescence during ATRI. These findings indicate that 1 has an ER-related action on Arabidopsis stomata that bypasses the COI1-JAZ signaling module. It may be possible to suppress the action of 1 on stomata without impairing plant defense responses against herbivores.", "classifications": [ { "id": "Sodeoka", "label": "Group Sodeoka", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Minoru", "last_name": "Ueda", "name": null }, { "creator_type": "author", "first_name": "Syusuke", "last_name": "Egoshi", "name": null }, { "creator_type": "author", "first_name": "Kosuke", "last_name": "Dodo", "name": null }, { "creator_type": "author", "first_name": "Yasuhiro", "last_name": "Ishimaru", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Yamakoshi", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Nakano", "name": null }, { "creator_type": "author", "first_name": "Yousuke", "last_name": "Takaoka", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Tsukiji", "name": null }, { "creator_type": "author", "first_name": "Mikiko", "last_name": "Sodeoka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/acscentsci.7b00099" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "28573209" } }, "mesh": [], "publication": { "conference_name": null, "date": "2017 May 24", "date_precision": "day", "issue": "5", "normalized_date": "2017-05-24", "pages": "462-472", "proceedings_title": null, "publisher": "", "title": "ACS Central Science", "volume": "3", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Noncanonical Function of a Small-Molecular Virulence Factor Coronatine against Plant Immunity: An In Vivo Raman Imaging Approach.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Cell-cell signaling is subject to variability in the extracellular volume, cell number, and dilution that potentially increase uncertainty in the absolute concentrations of the extracellular signaling molecules. To direct cell aggregation, the social amoebae Dictyostelium discoideum collectively give rise to oscillations and waves of cyclic adenosine 3',5'-monophosphate (cAMP) under a wide range of cell density. To date, the systems-level mechanism underlying the robustness is unclear. By using quantitative live-cell imaging, here we show that the magnitude of the cAMP relay response of individual cells is determined by fold change in the extracellular cAMP concentrations. The range of cell density and exogenous cAMP concentrations that support oscillations at the population level agrees well with conditions that support a large fold-change-dependent response at the single-cell level. Mathematical analysis suggests that invariance of the oscillations to density transformation is a natural outcome of combining secrete-and-sense systems with a fold-change detection mechanism.", "classifications": [ { "id": "Sawai", "label": "Group Sawai", "parent": "Sawai", "type": "group" }, { "id": "Sawai", "label": "Team Sawai", "type": "team" } ], "creators": [ { "creator_type": "contributor", "first_name": "Keita", "last_name": "Kamino", "name": null }, { "creator_type": "contributor", "first_name": "Yohei", "last_name": "Kondo", "name": null }, { "creator_type": "contributor", "first_name": "Akihiko", "last_name": "Nakajima", "name": null }, { "creator_type": "contributor", "first_name": "Mai", "last_name": "Honda-Kitahara", "name": null }, { "creator_type": "contributor", "first_name": "Kunihiko", "last_name": "Kaneko", "name": null }, { "creator_type": "contributor", "first_name": "Satoshi", "last_name": "Sawai", "name": null } ], "identifiers": { "doi": { "normalized": "10.1073/pnas.1702181114" }, "pmcid": { "normalized": "PMC5448168" }, "pmid": { "normalized": "28495969" } }, "mesh": [ { "descriptor": "Cyclic AMP", "descriptor_ui": "D000242", "major_topic": false }, { "descriptor": "Dictyostelium", "descriptor_ui": "D004023", "major_topic": false }, { "descriptor": "Paracrine Communication", "descriptor_ui": "D019899", "major_topic": true } ], "publication": { "conference_name": null, "date": "2017 May 23", "date_precision": "day", "issue": "21", "normalized_date": "2017-05-23", "pages": "E4149-E4157", "proceedings_title": null, "publisher": "", "title": "Proceedings of the National Academy of Sciences of the United States of America", "volume": "114", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Fold-change detection and scale invariance of cell-cell signaling in social amoeba.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "NHC-Au(I) complexes were used to prepare stable, water-soluble, NHC-protected gold nanoparticles. The water-soluble, charged nature of the nanoparticles permitted analysis by polyacrylamide gel electrophoresis (PAGE), which showed that the nanoparticles were highly monodisperse, with tunable core diameters between 2.0 and 3.3 nm depending on the synthesis conditions. Temporal, thermal, and chemical stability of the nanoparticles were determined to be high. Treatment with thiols caused etching of the particles after 24 h; however larger plasmonic particles showed greater resistance to thiol treatment. These water-soluble, bio-compatible nanoparticles are promising candidates for use in photoacoustic imaging, with even the smallest nanoparticles giving reliable photoacoustic signals.", "classifications": [ { "id": "Nanbo", "label": "Group Nanbo", "parent": "Tsuchiya", "type": "group" }, { "id": "Tsuchiya", "label": "Team Tsuchiya", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Kirsi", "last_name": "Salorinne", "name": null }, { "creator_type": "author", "first_name": "Renee W. Y.", "last_name": "Man", "name": null }, { "creator_type": "author", "first_name": "Chien-Hung", "last_name": "Li", "name": null }, { "creator_type": "author", "first_name": "Masayasu", "last_name": "Taki", "name": null }, { "creator_type": "author", "first_name": "Masakazu", "last_name": "Nambo", "name": null }, { "creator_type": "author", "first_name": "Cathleen M.", "last_name": "Crudden", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/anie.201701605" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "28407403" } }, "mesh": [], "publication": { "conference_name": null, "date": "2017 May 22", "date_precision": "day", "issue": "22", "normalized_date": "2017-05-22", "pages": "6198-6202", "proceedings_title": null, "publisher": "", "title": "Angewandte Chemie (International ed. in English)", "volume": "56", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Water-Soluble N-Heterocyclic Carbene-Protected Gold Nanoparticles: Size-Controlled Synthesis, Stability, and Optical Properties.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The use of synthetic biomarkers is an emerging technique to improve disease diagnosis. Here, we report a novel design strategy that uses analyte-responsive acetaminophen (APAP) to expand the catalogue of analytes available for synthetic biomarker development. As proof-of-concept, we designed hydrogen peroxide (H(2) O(2) )-responsive APAP (HR-APAP) and succeeded in H(2) O(2) detection with cellular and animal experiments. In fact, for blood samples following HR-APAP injection, we demonstrated that the plasma concentration ratio [APAP+APAP conjugates]/[HR-APAP] accurately reflects in vivo differences in H(2) O(2) levels. We anticipate that our practical methodology will be broadly useful for the preparation of various synthetic biomarkers.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Nishihara", "name": null }, { "creator_type": "author", "first_name": "Joe", "last_name": "Inoue", "name": null }, { "creator_type": "author", "first_name": "Sho", "last_name": "Tabata", "name": null }, { "creator_type": "author", "first_name": "Shinnosuke", "last_name": "Murakami", "name": null }, { "creator_type": "author", "first_name": "Takamasa", "last_name": "Ishikawa", "name": null }, { "creator_type": "author", "first_name": "Natsumi", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Shinji", "last_name": "Fukuda", "name": null }, { "creator_type": "author", "first_name": "Masaru", "last_name": "Tomita", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/cbic.201700023" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "28236354" } }, "mesh": [ { "descriptor": "Acetaminophen", "descriptor_ui": "D000082", "major_topic": false }, { "descriptor": "Analgesics, Non-Narcotic", "descriptor_ui": "D018712", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Biomarkers", "descriptor_ui": "D015415", "major_topic": false }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Chromatography, Liquid", "descriptor_ui": "D002853", "major_topic": false }, { "descriptor": "Hydrogen Peroxide", "descriptor_ui": "D006861", "major_topic": false }, { "descriptor": "Lipopolysaccharides", "descriptor_ui": "D008070", "major_topic": false }, { "descriptor": "Liver", "descriptor_ui": "D008099", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Oxidants", "descriptor_ui": "D016877", "major_topic": false }, { "descriptor": "Tandem Mass Spectrometry", "descriptor_ui": "D053719", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 May 18", "date_precision": "day", "issue": "10", "normalized_date": "2017-05-18", "pages": "910-913", "proceedings_title": null, "publisher": "", "title": "Chembiochem : a European journal of chemical biology", "volume": "18", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Synthetic Biomarker Design by Using Analyte-Responsive Acetaminophen.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Thymidine phosphorylase (TP), a rate-limiting enzyme in thymidine catabolism, plays a pivotal role in tumor progression; however, the mechanisms underlying this role are not fully understood. Here, we found that TP-mediated thymidine catabolism could supply the carbon source in the glycolytic pathway and thus contribute to cell survival under conditions of nutrient deprivation. In TP-expressing cells, thymidine was converted to metabolites, including glucose 6-phosphate, lactate, 5-phospho-alpha-D-ribose 1-diphosphate, and serine, via the glycolytic pathway both in vitro and in vivo. These thymidine-derived metabolites were required for the survival of cells under low-glucose conditions. Furthermore, activation of thymidine catabolism was observed in human gastric cancer. These findings demonstrate that thymidine can serve as a glycolytic pathway substrate in human cancer cells.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Sho", "last_name": "Tabata", "name": null }, { "creator_type": "author", "first_name": "Masatatsu", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Hisatsugu", "last_name": "Goto", "name": null }, { "creator_type": "author", "first_name": "Akiyoshi", "last_name": "Hirayama", "name": null }, { "creator_type": "author", "first_name": "Maki", "last_name": "Ohishi", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Kuramoto", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Mitsuhashi", "name": null }, { "creator_type": "author", "first_name": "Ryuji", "last_name": "Ikeda", "name": null }, { "creator_type": "author", "first_name": "Misako", "last_name": "Haraguchi", "name": null }, { "creator_type": "author", "first_name": "Kohichi", "last_name": "Kawahara", "name": null }, { "creator_type": "author", "first_name": "Yoshinari", "last_name": "Shinsato", "name": null }, { "creator_type": "author", "first_name": "Kentaro", "last_name": "Minami", "name": null }, { "creator_type": "author", "first_name": "Atsuro", "last_name": "Saijo", "name": null }, { "creator_type": "author", "first_name": "Masaki", "last_name": "Hanibuchi", "name": null }, { "creator_type": "author", "first_name": "Yasuhiko", "last_name": "Nishioka", "name": null }, { "creator_type": "author", "first_name": "Saburo", "last_name": "Sone", "name": null }, { "creator_type": "author", "first_name": "Hiroyasu", "last_name": "Esumi", "name": null }, { "creator_type": "author", "first_name": "Masaru", "last_name": "Tomita", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Tatsuhiko", "last_name": "Furukawa", "name": null }, { "creator_type": "author", "first_name": "Shin-Ichi", "last_name": "Akiyama", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.celrep.2017.04.061" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "28514652" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Carbon", "descriptor_ui": "D002244", "major_topic": false }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Cell Proliferation", "descriptor_ui": "D049109", "major_topic": false }, { "descriptor": "Deoxyribose", "descriptor_ui": "D003855", "major_topic": false }, { "descriptor": "Glycolysis", "descriptor_ui": "D006019", "major_topic": false }, { "descriptor": "Human Umbilical Vein Endothelial Cells", "descriptor_ui": "D061307", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Nutritional Status", "descriptor_ui": "D009752", "major_topic": false }, { "descriptor": "Phosphorylation", "descriptor_ui": "D010766", "major_topic": false }, { "descriptor": "Stomach Neoplasms", "descriptor_ui": "D013274", "major_topic": false }, { "descriptor": "Survival Analysis", "descriptor_ui": "D016019", "major_topic": false }, { "descriptor": "Thymidine", "descriptor_ui": "D013936", "major_topic": false }, { "descriptor": "Thymidine Phosphorylase", "descriptor_ui": "D013939", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 May 16", "date_precision": "day", "issue": "7", "normalized_date": "2017-05-16", "pages": "1313-1321", "proceedings_title": null, "publisher": "", "title": "Cell reports", "volume": "19", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Thymidine Catabolism as a Metabolic Strategy for Cancer Survival.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The Golgi apparatus is a membrane-bounded organelle with the characteristic shape of a series of stacked flat cisternae. During mitosis in mammalian cells, the Golgi apparatus is once fragmented into small vesicles and then reassembled to form the characteristic shape again in each daughter cell. The mechanism and details of the reassembly process remain elusive. Here, by the physical simulation of a coarse-grained membrane model, we reconstructed the three-dimensional morphological dynamics of the Golgi reassembly process. Considering the stability of the interphase Golgi shape, we introduce two hypothetical mechanisms-the Golgi rim stabilizer protein and curvature-dependent restriction on membrane fusion-into the general biomembrane model. We show that the characteristic Golgi shape is spontaneously organized from the assembly of vesicles by proper tuning of the two additional mechanisms, i.e., the Golgi reassembly process is modeled as self-organization. We also demonstrate that the fine Golgi shape forms via a balance of three reaction speeds: vesicle aggregation, membrane fusion, and shape relaxation. Moreover, the membrane fusion activity decreases thickness and the number of stacked cisternae of the emerging shapes.", "classifications": [ { "id": "Mochizuki", "label": "Group Mochizuki", "parent": "Eiraku", "type": "group" }, { "id": "Eiraku", "label": "Team Eiraku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Masashi", "last_name": "Tachikawa", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Mochizuki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1073/pnas.1619264114" }, "pmcid": { "normalized": "PMC5441826" }, "pmid": { "normalized": "28461510" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Computer Simulation", "descriptor_ui": "D003198", "major_topic": false }, { "descriptor": "Golgi Apparatus", "descriptor_ui": "D006056", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Membrane Fusion", "descriptor_ui": "D008561", "major_topic": false }, { "descriptor": "Mitosis", "descriptor_ui": "D008938", "major_topic": false }, { "descriptor": "Models, Biological", "descriptor_ui": "D008954", "major_topic": false }, { "descriptor": "Protein Stability", "descriptor_ui": "D055550", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 May 16", "date_precision": "day", "issue": "20", "normalized_date": "2017-05-16", "pages": "5177-5182", "proceedings_title": null, "publisher": "", "title": "Proceedings of the National Academy of Sciences of the United States of America", "volume": "114", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Golgi apparatus self-organizes into the characteristic shape via postmitotic reassembly dynamics.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Self-motion of an oil droplet was investigated on a sodium dodecyl sulfate (SDS) aqueous phase. With an increase in the concentration of SDS, the nature of self-motion of a butyl salicylate (BS) droplet as the oil droplet was changed, i.e., no motion, reciprocation with a small amplitude, and reciprocation with a large amplitude, which was a value close to the half-length of the chamber. The interfacial tension, contact angle, and convective flow around the droplet were measured to clarify the driving force of reciprocation. The mechanisms of two types of reciprocation and mode-change were discussed in terms of the adsorption of SDS molecules at the BS/water interface and the dissolution of a mixture of BS and SDS into the bulk phase, the convective flow, and the Young's equation. The features of reciprocation and mode-change depending on the concentration of SDS were qualitatively reproduced by numerical calculation based on an equation of motion and the kinetics of SDS and BS at the air/aqueous interface.", "classifications": [ { "id": "Nagayama", "label": "Group Nagayama", "parent": "Fujiwara", "type": "group" }, { "id": "Fujiwara", "label": "Team Fujiwara", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yusuke", "last_name": "Satoh", "name": null }, { "creator_type": "author", "first_name": "Yoshimi", "last_name": "Sogabe", "name": null }, { "creator_type": "author", "first_name": "Katsuhiko", "last_name": "Kayahara", "name": null }, { "creator_type": "author", "first_name": "Shinpei", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Masaharu", "last_name": "Nagayama", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Nakata", "name": null } ], "identifiers": { "doi": { "normalized": "10.1039/c7sm00252a" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "28436513" } }, "mesh": [], "publication": { "conference_name": null, "date": "2017 May 14", "date_precision": "day", "issue": "18", "normalized_date": "2017-05-14", "pages": "3422-3430", "proceedings_title": null, "publisher": "", "title": "Soft matter", "volume": "13", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Self-inverted reciprocation of an oil droplet on a surfactant solution.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Citrullinemia type 1 (CTLN1) is a urea cycle disorder (UCD) caused by mutations of the ASS1 gene, which is responsible for production of the enzyme argininosuccinate synthetase (ASS), and classically presented as life-threatening hyperammonemia in newborns. Therapeutic options are limited, and neurological sequelae may persist. To understand the pathophysiology and find novel treatments, induced pluripotent stem cells (iPSCs) were generated from a CTLN1 patient and differentiated into hepatocyte-like cells (HLCs). CTLN1-HLCs have lower ureagenesis, recapitulating part of the patient's phenotype. l-arginine, an amino acid clinically used for UCD treatment, improved this phenotype in vitro. Metabolome analysis revealed an increase in tricarboxylic acid (TCA) cycle metabolites in CTLN1, suggesting a connection between CTLN1 and the TCA cycle. This CTLN1-iPSC model improves the understanding of CTLN1 pathophysiology and can be used to pursue new therapeutic approaches.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Elena Yukie", "last_name": "Yoshitoshi-Uebayashi", "name": null }, { "creator_type": "author", "first_name": "Taro", "last_name": "Toyoda", "name": null }, { "creator_type": "author", "first_name": "Katsutaro", "last_name": "Yasuda", "name": null }, { "creator_type": "author", "first_name": "Maki", "last_name": "Kotaka", "name": null }, { "creator_type": "author", "first_name": "Keiko", "last_name": "Nomoto", "name": null }, { "creator_type": "author", "first_name": "Keisuke", "last_name": "Okita", "name": null }, { "creator_type": "author", "first_name": "Kentaro", "last_name": "Yasuchika", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Okamoto", "name": null }, { "creator_type": "author", "first_name": "Noriyuki", "last_name": "Takubo", "name": null }, { "creator_type": "author", "first_name": "Toshiya", "last_name": "Nishikubo", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Shinji", "last_name": "Uemoto", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Osafune", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.bbrc.2017.03.037" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "28302489" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Arginine", "descriptor_ui": "D001120", "major_topic": false }, { "descriptor": "Argininosuccinate Synthase", "descriptor_ui": "D001124", "major_topic": false }, { "descriptor": "Base Sequence", "descriptor_ui": "D001483", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Citric Acid Cycle", "descriptor_ui": "D002952", "major_topic": false }, { "descriptor": "Citrullinemia", "descriptor_ui": "D020159", "major_topic": false }, { "descriptor": "Gene Expression Profiling", "descriptor_ui": "D020869", "major_topic": false }, { "descriptor": "Gene Expression Regulation", "descriptor_ui": "D005786", "major_topic": false }, { "descriptor": "Hepatocytes", "descriptor_ui": "D022781", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Induced Pluripotent Stem Cells", "descriptor_ui": "D057026", "major_topic": false }, { "descriptor": "Karyotyping", "descriptor_ui": "D007621", "major_topic": false }, { "descriptor": "Metabolome", "descriptor_ui": "D055442", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred NOD", "descriptor_ui": "D016688", "major_topic": false }, { "descriptor": "Models, Biological", "descriptor_ui": "D008954", "major_topic": false }, { "descriptor": "Primary Cell Culture", "descriptor_ui": "D061251", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Urea", "descriptor_ui": "D014508", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 May 6", "date_precision": "day", "issue": "3", "normalized_date": "2017-05-06", "pages": "613-619", "proceedings_title": null, "publisher": "", "title": "Biochemical and biophysical research communications", "volume": "486", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Modelling urea-cycle disorder citrullinemia type 1 with disease-specific iPSCs.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The generation of tumor-initiating cells during colon carcinogenesis is associated with the dysregulation of Wnt signaling, which is known to act on Lgr5-positive intestinal stem cells. Here, using single-cell qPCR analysis, we identified a subset of Lgr5-positive stem cells that emerged during tumorigenesis in a mouse model of colon cancer. These tumor-specific Lgr5-positive cells expressed low levels of Ceacam1 and increased levels of a specific subset of Wnt targets and showed enhanced tumorigenicity. Among the Wnt targets that were specifically expressed, the long isoform of Tcf1 was required for the proliferation of tumor organoids and drove a unique Wnt target gene expression profile. Tcf1 expression increased at an early stage of colon carcinogenesis and was associated with the nuclear accumulation of beta-catenin, underscoring the importance of the induction of Tcf1 expression in generating tumorigenic colon stem cells.", "classifications": [ { "id": "Okamoto", "label": "Group Okamoto", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Daisuke", "last_name": "Shiokawa", "name": null }, { "creator_type": "author", "first_name": "Ai", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Hirokazu", "last_name": "Ohata", "name": null }, { "creator_type": "author", "first_name": "Michihiro", "last_name": "Mutoh", "name": null }, { "creator_type": "author", "first_name": "Shigeki", "last_name": "Sekine", "name": null }, { "creator_type": "author", "first_name": "Mamoru", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Tatsuhiro", "last_name": "Shibata", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Nakagama", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Okamoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.celrep.2017.04.017" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "28467911" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Carcinogenesis", "descriptor_ui": "D063646", "major_topic": false }, { "descriptor": "Colonic Neoplasms", "descriptor_ui": "D003110", "major_topic": false }, { "descriptor": "Gene Expression Regulation, Neoplastic", "descriptor_ui": "D015972", "major_topic": false }, { "descriptor": "Hepatocyte Nuclear Factor 1-alpha", "descriptor_ui": "D051538", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Neoplastic Stem Cells", "descriptor_ui": "D014411", "major_topic": false }, { "descriptor": "Protein Isoforms", "descriptor_ui": "D020033", "major_topic": false }, { "descriptor": "Receptors, G-Protein-Coupled", "descriptor_ui": "D043562", "major_topic": false }, { "descriptor": "Wnt Proteins", "descriptor_ui": "D051153", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 May 2", "date_precision": "day", "issue": "5", "normalized_date": "2017-05-02", "pages": "981-994", "proceedings_title": null, "publisher": "", "title": "Cell reports", "volume": "19", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "The Induction of Selected Wnt Target Genes by Tcf1 Mediates Generation of Tumorigenic Colon Stem Cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Quantifying global tissue deformation patterns is essential for understanding how organ-specific morphology is generated during development and regeneration. However, due to imaging difficulties and complex morphology, little is known about deformation dynamics for most vertebrate organs such as the brain and heart. To better understand these dynamics, we propose a method to precisely reconstruct global deformation patterns for three-dimensional morphogenesis of curved epithelial sheets using positional data from labeled cells representing only 1-10% of the entire tissue with limited resolution. By combining differential-geometrical and Bayesian frameworks, the method is applicable to any morphology described with arbitrary coordinates, and ensures the feasibility of analyzing many vertebrate organs. Application to data from chick forebrain morphogenesis demonstrates that our method provides not only a quantitative description of tissue deformation dynamics but also predictions of the mechanisms that determine organ-specific morphology, which could form the basis for the multi-scale understanding of organ morphogenesis.Quantifying deformation patterns of curved epithelial sheets is challenging owing to imaging difficulties. Here the authors develop a method to obtain a quantitative description of 3D tissue deformation dynamics from a small set of cell positional data and applied it to chick forebrain morphogenesis.", "classifications": [ { "id": "Morishita", "label": "Group Morishita", "parent": "Morishita", "type": "group" }, { "id": "Morishita", "label": "Team Morishita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yoshihiro", "last_name": "Morishita", "name": null }, { "creator_type": "author", "first_name": "Ken-Ichi", "last_name": "Hironaka", "name": null }, { "creator_type": "author", "first_name": "Sang-Woo", "last_name": "Lee", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Jin", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Ohtsuka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41467-017-00023-7" }, "pmcid": { "normalized": "PMC5432036" }, "pmid": { "normalized": "28465614" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Anisotropy", "descriptor_ui": "D016880", "major_topic": false }, { "descriptor": "Brain", "descriptor_ui": "D001921", "major_topic": false }, { "descriptor": "Calcium-Binding Proteins", "descriptor_ui": "D002135", "major_topic": false }, { "descriptor": "Chick Embryo", "descriptor_ui": "D002642", "major_topic": false }, { "descriptor": "Computer Simulation", "descriptor_ui": "D003198", "major_topic": false }, { "descriptor": "Epithelial Cells", "descriptor_ui": "D004847", "major_topic": false }, { "descriptor": "Epithelium", "descriptor_ui": "D004848", "major_topic": false }, { "descriptor": "Gene Expression", "descriptor_ui": "D015870", "major_topic": false }, { "descriptor": "Genes, Reporter", "descriptor_ui": "D017930", "major_topic": false }, { "descriptor": "Green Fluorescent Proteins", "descriptor_ui": "D049452", "major_topic": false }, { "descriptor": "Image Processing, Computer-Assisted", "descriptor_ui": "D007091", "major_topic": false }, { "descriptor": "Models, Anatomic", "descriptor_ui": "D008953", "major_topic": true }, { "descriptor": "Organogenesis", "descriptor_ui": "D038081", "major_topic": false }, { "descriptor": "Recombinant Fusion Proteins", "descriptor_ui": "D011993", "major_topic": false }, { "descriptor": "Staining and Labeling", "descriptor_ui": "D013194", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 May 2", "date_precision": "day", "issue": "1", "normalized_date": "2017-05-02", "pages": "15", "proceedings_title": null, "publisher": "", "title": "Nature communications", "volume": "8", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Reconstructing 3D deformation dynamics for curved epithelial sheet morphogenesis from positional data of sparsely-labeled cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Naive pluripotent stem cells (PSCs) utilize both glycolysis and oxidative phosphorylation (OXPHOS) to satisfy their metabolic demands. However, it is unclear how somatic cells acquire this hybrid energy metabolism during reprogramming toward naive pluripotency. Here, we show that when transduced with Oct4, Sox2, and Klf4 (OSK) into murine fibroblasts, Zic3 and Esrrb synergistically enhance the reprogramming efficiency by regulating cellular metabolic pathways. These two transcription factors (TFs) cooperatively activate glycolytic metabolism independently of hypoxia inducible factors (HIFs). In contrast, the regulatory modes of the TFs on OXPHOS are antagonistic: Zic3 represses OXPHOS, whereas Esrrb activates it. Therefore, when introduced with Zic3, Esrrb restores OXPHOS activity, which is essential for efficient reprogramming. In addition, Esrrb-mediated OXPHOS activation is critical for the conversion of primed PSCs into the naive state. Our study suggests that the combinatorial function of TFs achieves an appropriate balance of metabolic pathways to induce naive PSCs.", "classifications": [ { "id": "Yamamoto", "label": "Group Yamamoto", "parent": "Toyoshima", "type": "group" }, { "id": "Toyoshima", "label": "Team Toyoshima", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Masamitsu", "last_name": "Sone", "name": null }, { "creator_type": "author", "first_name": "Nobuhiro", "last_name": "Morone", "name": null }, { "creator_type": "author", "first_name": "Tomonori", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Akito", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Keisuke", "last_name": "Okita", "name": null }, { "creator_type": "author", "first_name": "Knut", "last_name": "Woltjen", "name": null }, { "creator_type": "author", "first_name": "Masato", "last_name": "Nakagawa", "name": null }, { "creator_type": "author", "first_name": "John E.", "last_name": "Heuser", "name": null }, { "creator_type": "author", "first_name": "Yasuhiro", "last_name": "Yamada", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Yamanaka", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Yamamoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.cmet.2017.04.017" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "28467928" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Cellular Reprogramming", "descriptor_ui": "D065150", "major_topic": true }, { "descriptor": "Fibroblasts", "descriptor_ui": "D005347", "major_topic": false }, { "descriptor": "Glycolysis", "descriptor_ui": "D006019", "major_topic": true }, { "descriptor": "Homeodomain Proteins", "descriptor_ui": "D018398", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Induced Pluripotent Stem Cells", "descriptor_ui": "D057026", "major_topic": false }, { "descriptor": "Kruppel-Like Factor 4", "descriptor_ui": "D000090062", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Inbred ICR", "descriptor_ui": "D008813", "major_topic": false }, { "descriptor": "Oxidative Phosphorylation", "descriptor_ui": "D010085", "major_topic": true }, { "descriptor": "Receptors, Estrogen", "descriptor_ui": "D011960", "major_topic": false }, { "descriptor": "Transcription Factors", "descriptor_ui": "D014157", "major_topic": false }, { "descriptor": "Up-Regulation", "descriptor_ui": "D015854", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 May 2", "date_precision": "day", "issue": "5", "normalized_date": "2017-05-02", "pages": "1103-1117.e6", "proceedings_title": null, "publisher": "", "title": "Cell metabolism", "volume": "25", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Hybrid Cellular Metabolism Coordinated by Zic3 and Esrrb Synergistically Enhances Induction of Naive Pluripotency.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Mutations in succinate dehydrogenase B (SDHB) gene are frequently observed in several tumors and associated with poor prognosis in these tumors. Therefore, drugs effective for SDHB-deficient tumors could fulfill an unmet medical need. In addition, such drugs would have an advantage in that selection of patients with SDHB-mutant cancer could increase the probability of success in clinical trials. Currently, however, the characteristics of SDHB-deficient cancers are not completely understood. Here, we established SDHB knockout cancer cell lines from human colon cancer HCT116 cells using the clustered regularly interspaced short palindromic repeat (CRISPR)/Cas9 knockout system, and clarified its metabolic characteristics.In the SDHB knockout cells, succinate was accumulated and fumarate was decreased. The oxygen consumption rate was decreased while the extracellular acidification rate was increased in the SDHB knockout cells. Accordingly, an enhanced glycolysis pathway in the SDHB knockout cells was demonstrated by metabolomics analysis. Tracer experiments showed bidirectional metabolic flow in the tricarboxylic acid (TCA) cycle, possibly to maintain the necessary amounts of metabolites in the SDHB knockout cells. The proliferation of SDHB knockout cells was suppressed by a glycolysis inhibitor but not by a mitochondrial inhibitor. Additionally, partial dependence on glutaminolysis was observed in the SDHB knockout cells. Compound screening revealed that a bromodomain and extra-terminal (BET) inhibitor, which downregulated c-Myc, suppressed the growth of the SDHB knockout cells more potently than that of control cells. These findings provide an understanding of the metabolic characteristics of SDHB-deficient cancer and its vulnerabilities, which may lead to new therapeutic options.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Satoshi", "last_name": "Kitazawa", "name": null }, { "creator_type": "author", "first_name": "Shunsuke", "last_name": "Ebara", "name": null }, { "creator_type": "author", "first_name": "Ayumi", "last_name": "Ando", "name": null }, { "creator_type": "author", "first_name": "Yuji", "last_name": "Baba", "name": null }, { "creator_type": "author", "first_name": "Yoshinori", "last_name": "Satomi", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Takahito", "last_name": "Hara", "name": null } ], "identifiers": { "doi": { "normalized": "10.18632/oncotarget.15959" }, "pmcid": { "normalized": "PMC5438703" }, "pmid": { "normalized": "28423651" } }, "mesh": [ { "descriptor": "Antineoplastic Agents", "descriptor_ui": "D000970", "major_topic": false }, { "descriptor": "Azepines", "descriptor_ui": "D001381", "major_topic": false }, { "descriptor": "Benzodiazepines", "descriptor_ui": "D001569", "major_topic": false }, { "descriptor": "Citric Acid Cycle", "descriptor_ui": "D002952", "major_topic": false }, { "descriptor": "CRISPR-Cas Systems", "descriptor_ui": "D064113", "major_topic": false }, { "descriptor": "Dehydroepiandrosterone", "descriptor_ui": "D003687", "major_topic": false }, { "descriptor": "Fumarates", "descriptor_ui": "D005650", "major_topic": false }, { "descriptor": "Gene Knockout Techniques", "descriptor_ui": "D055786", "major_topic": false }, { "descriptor": "Glucosephosphate Dehydrogenase", "descriptor_ui": "D005954", "major_topic": false }, { "descriptor": "Glycolysis", "descriptor_ui": "D006019", "major_topic": false }, { "descriptor": "HCT116 Cells", "descriptor_ui": "D045325", "major_topic": false }, { "descriptor": "Heterocyclic Compounds, 4 or More Rings", "descriptor_ui": "D006576", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Isoenzymes", "descriptor_ui": "D007527", "major_topic": false }, { "descriptor": "L-Lactate Dehydrogenase", "descriptor_ui": "D007770", "major_topic": false }, { "descriptor": "Lactate Dehydrogenase 5", "descriptor_ui": "D000080864", "major_topic": false }, { "descriptor": "Metabolomics", "descriptor_ui": "D055432", "major_topic": false }, { "descriptor": "Mitochondria", "descriptor_ui": "D008928", "major_topic": false }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": false }, { "descriptor": "Neoplasms", "descriptor_ui": "D009369", "major_topic": false }, { "descriptor": "Oxygen Consumption", "descriptor_ui": "D010101", "major_topic": false }, { "descriptor": "Phenformin", "descriptor_ui": "D010629", "major_topic": false }, { "descriptor": "Phosphoglycerate Dehydrogenase", "descriptor_ui": "D050543", "major_topic": false }, { "descriptor": "Proto-Oncogene Proteins c-myc", "descriptor_ui": "D016271", "major_topic": false }, { "descriptor": "RNA Interference", "descriptor_ui": "D034622", "major_topic": false }, { "descriptor": "RNA, Small Interfering", "descriptor_ui": "D034741", "major_topic": false }, { "descriptor": "Succinate Dehydrogenase", "descriptor_ui": "D013385", "major_topic": false }, { "descriptor": "Succinic Acid", "descriptor_ui": "D019802", "major_topic": false }, { "descriptor": "Triazoles", "descriptor_ui": "D014230", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Apr 25", "date_precision": "day", "issue": "17", "normalized_date": "2017-04-25", "pages": "28922-28938", "proceedings_title": null, "publisher": "", "title": "Oncotarget", "volume": "8", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Succinate dehydrogenase B-deficient cancer cells are highly sensitive to bromodomain and extra-terminal inhibitors.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Eleutherococcus sieboldianus (Makino) Koidz. is a local product from the area in and around Yonezawa City in Yamagata Prefecture, Japan. It has been used as a medicinal plant for a long time. We isolated and identified four types of flavonoid glycosides [astragalin (1), isoquercetin (2), rhamnocitrin 3-O-glucoside (3), and nicotiflorin (4)], a triterpene [methyl hederagenin (5)], and three types of triterpene glycosides [δ-hederin (6), echinocystic acid 3-O-arabinoside (7), and cauloside B (8)] from the methanol extract of E. sieboldianus, which regulates lipid accumulation in 3T3-L1 preadipocytes. Among the compounds isolated, 2 and 8 up- and down-regulated lipid accumulation and insulin induced adipocyte differentiation in 3T3-L1 preadipocytes. Compound 2 induced up-regulation of lipid accumulation and decreased adipocyte size, while 8 down-regulated lipid accumulations without decreasing cell size. Additionally, 2 increased adipogenic proteins [peroxisome proliferator-activated receptor γ (PPARγ), CCAAT/enhancer-binding protein alpha (C/EBPα), and fatty-acid-binding protein 4 (FABP4)]. In contrast, 8 decreased the levels of all adipogenic proteins and glucose transporter type 4 (GLUT4), but increased adiponectin.", "classifications": [ { "id": "Suzuki", "label": "Group Suzuki", "parent": "Takekawa", "type": "group" }, { "id": "Takekawa", "label": "Team Takekawa", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Atsuyoshi", "last_name": "Nishina", "name": null }, { "creator_type": "author", "first_name": "Masaya", "last_name": "Itagaki", "name": null }, { "creator_type": "author", "first_name": "Yuusuke", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Mamoru", "last_name": "Koketsu", "name": null }, { "creator_type": "author", "first_name": "Masayuki", "last_name": "Ninomiya", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Hayakawa", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Kuroda", "name": null }, { "creator_type": "author", "first_name": "Hirokazu", "last_name": "Kimura", "name": null } ], "identifiers": { "doi": { "normalized": "10.3390/molecules22040671" }, "pmcid": { "normalized": "PMC6154646" }, "pmid": { "normalized": "28441735" } }, "mesh": [ { "descriptor": "3T3-L1 Cells", "descriptor_ui": "D041721", "major_topic": false }, { "descriptor": "Adipocytes", "descriptor_ui": "D017667", "major_topic": false }, { "descriptor": "Adipogenesis", "descriptor_ui": "D050156", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Anti-Obesity Agents", "descriptor_ui": "D019440", "major_topic": false }, { "descriptor": "Cell Survival", "descriptor_ui": "D002470", "major_topic": false }, { "descriptor": "Drug Evaluation, Preclinical", "descriptor_ui": "D004353", "major_topic": false }, { "descriptor": "Eleutherococcus", "descriptor_ui": "D028001", "major_topic": false }, { "descriptor": "Flavonoids", "descriptor_ui": "D005419", "major_topic": false }, { "descriptor": "Lipid Metabolism", "descriptor_ui": "D050356", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Plant Extracts", "descriptor_ui": "D010936", "major_topic": false }, { "descriptor": "Plant Leaves", "descriptor_ui": "D018515", "major_topic": false }, { "descriptor": "Triterpenes", "descriptor_ui": "D014315", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Apr 22", "date_precision": "day", "issue": "4", "normalized_date": "2017-04-22", "pages": "", "proceedings_title": null, "publisher": "", "title": "Molecules (Basel, Switzerland)", "volume": "22", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Effects of Flavonoids and Triterpene Analogues from Leaves of Eleutherococcus sieboldianus (Makino) Koidz. 'Himeukogi' in 3T3-L1 Preadipocytes.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Novel double helices covalently bridged by cyclic boronate esters were synthesized from complementary dimers with an m-terphenyl backbone joined by a chiral or achiral phenylene linker bearing diethyl boronates and diols, respectively. The X-ray crystallographic analysis and variable-temperature NMR and circular dichroism measurements, along with theoretical calculations, revealed that the double helices function as a \"molecular rotor\" in which the cyclic boronate ester units rotate, yielding two stable rotamers at low temperatures. Moreover, our data indicates that the covalently bonded double helices can undergo a unique helix-inversion simultaneously with a rotational motion of the boronate esters.", "classifications": [ { "id": "Hijikata", "label": "Group Hijikata", "parent": "Tsuchiya", "type": "group" }, { "id": "Tsuchiya", "label": "Team Tsuchiya", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Hiroki", "last_name": "Iida", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Ohmura", "name": null }, { "creator_type": "author", "first_name": "Ryuta", "last_name": "Noda", "name": null }, { "creator_type": "author", "first_name": "Soichiro", "last_name": "Iwahana", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Katagiri", "name": null }, { "creator_type": "author", "first_name": "Naoki", "last_name": "Ousaka", "name": null }, { "creator_type": "author", "first_name": "Taku", "last_name": "Hayashi", "name": null }, { "creator_type": "author", "first_name": "Yuh", "last_name": "Hijikata", "name": null }, { "creator_type": "author", "first_name": "Stephan", "last_name": "Irle", "name": null }, { "creator_type": "author", "first_name": "Eiji", "last_name": "Yashima", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/asia.201700162" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "28198115" } }, "mesh": [], "publication": { "conference_name": null, "date": "2017 Apr 18", "date_precision": "day", "issue": "8", "normalized_date": "2017-04-18", "pages": "927-935", "proceedings_title": null, "publisher": "", "title": "Chemistry, an Asian journal", "volume": "12", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Double-Stranded Helical Oligomers Covalently Bridged by Rotary Cyclic Boronate Esters.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Solid tumours have oxygen gradients and areas of near and almost total anoxia. Hypoxia reduces sensitivity to 5-fluorouracil (5-FU)-chemotherapy for colorectal cancer (CRC). MicroRNAs (miRNAs) are hypoxia sensors and were altered consistently in six CRC cell lines (colon cancer: DLD-1, HCT116 and HT29; rectal cancer: HT55, SW837 and VACO4S) maintained in hypoxia (1 and 0.2% oxygen) compared with normoxia (20.9%). CRC cell lines also showed altered amino acid metabolism in hypoxia and hypoxia-responsive miRNAs were predicted to target genes in four metabolism pathways: beta-alanine; valine, leucine, iso-leucine; aminoacyl-tRNA; and alanine, aspartate, glutamate. MiR-210 was increased in hypoxic areas of CRC tissues and hypoxia-responsive miR-21 and miR-30d, but not miR-210, were significantly increased in 5-FU resistant CRCs. Treatment with miR-21 and miR-30d antagonists sensitized hypoxic CRC cells to 5-FU. Our data highlight the complexity and tumour heterogeneity caused by hypoxia. MiR-210 as a hypoxic biomarker, and the targeting of miR-21 and miR-30d and/or the amino acid metabolism pathways may offer translational opportunities.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Anke", "last_name": "Nijhuis", "name": null }, { "creator_type": "author", "first_name": "Hannah", "last_name": "Thompson", "name": null }, { "creator_type": "author", "first_name": "Julie", "last_name": "Adam", "name": null }, { "creator_type": "author", "first_name": "Alexandra", "last_name": "Parker", "name": null }, { "creator_type": "author", "first_name": "Luke", "last_name": "Gammon", "name": null }, { "creator_type": "author", "first_name": "Amy", "last_name": "Lewis", "name": null }, { "creator_type": "author", "first_name": "Jacob G.", "last_name": "Bundy", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Aisha", "last_name": "Jalaly", "name": null }, { "creator_type": "author", "first_name": "David", "last_name": "Propper", "name": null }, { "creator_type": "author", "first_name": "Rosemary", "last_name": "Jeffery", "name": null }, { "creator_type": "author", "first_name": "Nirosha", "last_name": "Suraweera", "name": null }, { "creator_type": "author", "first_name": "Sarah", "last_name": "McDonald", "name": null }, { "creator_type": "author", "first_name": "Mohamed A.", "last_name": "Thaha", "name": null }, { "creator_type": "author", "first_name": "Roger", "last_name": "Feakins", "name": null }, { "creator_type": "author", "first_name": "Robert", "last_name": "Lowe", "name": null }, { "creator_type": "author", "first_name": "Cleo L.", "last_name": "Bishop", "name": null }, { "creator_type": "author", "first_name": "Andrew", "last_name": "Silver", "name": null } ], "identifiers": { "doi": { "normalized": "10.1093/hmg/ddx059" }, "pmcid": { "normalized": "PMC5393147" }, "pmid": { "normalized": "28207045" } }, "mesh": [ { "descriptor": "Amino Acids", "descriptor_ui": "D000596", "major_topic": false }, { "descriptor": "Apoptosis", "descriptor_ui": "D017209", "major_topic": false }, { "descriptor": "Cell Hypoxia", "descriptor_ui": "D015687", "major_topic": false }, { "descriptor": "Colorectal Neoplasms", "descriptor_ui": "D015179", "major_topic": false }, { "descriptor": "Drug Resistance, Neoplasm", "descriptor_ui": "D019008", "major_topic": false }, { "descriptor": "Fluorouracil", "descriptor_ui": "D005472", "major_topic": false }, { "descriptor": "Gene Expression Regulation, Neoplastic", "descriptor_ui": "D015972", "major_topic": false }, { "descriptor": "Genetic Heterogeneity", "descriptor_ui": "D018740", "major_topic": false }, { "descriptor": "HCT116 Cells", "descriptor_ui": "D045325", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "MicroRNAs", "descriptor_ui": "D035683", "major_topic": false }, { "descriptor": "Oxygen", "descriptor_ui": "D010100", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Apr 15", "date_precision": "day", "issue": "8", "normalized_date": "2017-04-15", "pages": "1552-1564", "proceedings_title": null, "publisher": "", "title": "Human molecular genetics", "volume": "26", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Remodelling of microRNAs in colorectal cancer by hypoxia alters metabolism profiles and 5-fluorouracil resistance.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Protein-protein interactions (PPIs) are essential components of cellular function. Current fluorescence-based technologies to measure PPIs have limited dynamic range and quantitative reproducibility. Here, we describe a genetically-encoded PPI visualization system that harnesses the dynamics of condensed liquid-phase transitions to analyze protein interactions in living cells. The fluorescent protein Azami-Green and p62-PB1 domain when fused to PPI partners triggered a rapid concatenation/oligomerization process that drove the condensation of liquid-phase droplets for real-time analysis of the interaction with unlimited dynamic range in the fluorescence signal. Proof-of-principle studies revealed novel insights on the live cell dynamics of XIAP-Smac and ERK2-dimer interactions. A photoconvertible variant allowed time-resolved optical highlighting for PPI kinetic analysis. Our system, called Fluoppi, demonstrates the unique signal amplification properties of liquid-phase condensation to detect PPIs. The findings introduce a general method for discovery of novel PPIs and modulators of established PPIs.", "classifications": [ { "id": "Sawano", "label": "Group Sawano", "parent": "Shintaku", "type": "group" }, { "id": "Shintaku", "label": "Team Shintaku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Taku", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Seki", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Fukano", "name": null }, { "creator_type": "author", "first_name": "Asako", "last_name": "Sakaue-Sawano", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Karasawa", "name": null }, { "creator_type": "author", "first_name": "Misaki", "last_name": "Kubota", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Kurokawa", "name": null }, { "creator_type": "author", "first_name": "Ken", "last_name": "Inoue", "name": null }, { "creator_type": "author", "first_name": "Junichi", "last_name": "Akatsuka", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Miyawaki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/srep46380" }, "pmcid": { "normalized": "PMC5390312" }, "pmid": { "normalized": "28406179" } }, "mesh": [ { "descriptor": "Apoptosis Regulatory Proteins", "descriptor_ui": "D051017", "major_topic": false }, { "descriptor": "Binding Sites", "descriptor_ui": "D001665", "major_topic": false }, { "descriptor": "Biophysical Phenomena", "descriptor_ui": "D055592", "major_topic": false }, { "descriptor": "Fluorescent Dyes", "descriptor_ui": "D005456", "major_topic": false }, { "descriptor": "HeLa Cells", "descriptor_ui": "D006367", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Intracellular Signaling Peptides and Proteins", "descriptor_ui": "D047908", "major_topic": false }, { "descriptor": "Kinetics", "descriptor_ui": "D007700", "major_topic": false }, { "descriptor": "Mitochondrial Proteins", "descriptor_ui": "D024101", "major_topic": false }, { "descriptor": "Mitogen-Activated Protein Kinase 1", "descriptor_ui": "D019950", "major_topic": false }, { "descriptor": "Protein Domains", "descriptor_ui": "D000072417", "major_topic": false }, { "descriptor": "Protein Interaction Mapping", "descriptor_ui": "D025941", "major_topic": false }, { "descriptor": "Proteins", "descriptor_ui": "D011506", "major_topic": false }, { "descriptor": "RNA-Binding Proteins", "descriptor_ui": "D016601", "major_topic": false }, { "descriptor": "X-Linked Inhibitor of Apoptosis Protein", "descriptor_ui": "D051636", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Apr 13", "date_precision": "day", "issue": "", "normalized_date": "2017-04-13", "pages": "46380", "proceedings_title": null, "publisher": "", "title": "Scientific reports", "volume": "7", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Genetic visualization of protein interactions harnessing liquid phase transitions.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Sialidase cleaves sialic acids on the extracellular cell surface as well as inside the cell and is necessary for normal long-term potentiation (LTP) at mossy fiber-CA3 pyramidal cell synapses and for hippocampus-dependent spatial memory. Here, we investigated in detail the role of sialidase in memory processing. Sialidase activity measured with 4-methylumbelliferyl-α-d-N-acetylneuraminic acid (4MU-Neu5Ac) or 5-bromo-4-chloroindol-3-yl-α-d-N-acetylneuraminic acid (X-Neu5Ac) and Fast Red Violet LB was increased by high-K(+)-induced membrane depolarization. Sialidase activity was also increased by chemical LTP induction with forskolin and activation of BDNF signaling, non-NMDA receptors, or NMDA receptors. The increase in sialidase activity with neural excitation appears to be caused not by secreted sialidase or by an increase in sialidase expression but by a change in the subcellular localization of sialidase. Astrocytes as well as neurons are also involved in the neural activity-dependent increase in sialidase activity. Sialidase activity visualized with a benzothiazolylphenol-based sialic acid derivative (BTP3-Neu5Ac), a highly sensitive histochemical imaging probe for sialidase activity, at the CA3 stratum lucidum of rat acute hippocampal slices was immediately increased in response to LTP-inducible high-frequency stimulation on a time scale of seconds. To obtain direct evidence for sialic acid removal on the extracellular cell surface during neural excitation, the extracellular free sialic acid level in the hippocampus was monitored using in vivo microdialysis. The free sialic acid level was increased by high-K(+)-induced membrane depolarization. Desialylation also occurred during hippocampus-dependent memory formation in a contextual fear-conditioning paradigm. Our results show that neural activity-dependent desialylation by sialidase may be involved in hippocampal memory processing.", "classifications": [ { "id": "Suzuki", "label": "Group Suzuki", "parent": "Takekawa", "type": "group" }, { "id": "Takekawa", "label": "Team Takekawa", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Akira", "last_name": "Minami", "name": null }, { "creator_type": "author", "first_name": "Yuko", "last_name": "Meguro", "name": null }, { "creator_type": "author", "first_name": "Sayaka", "last_name": "Ishibashi", "name": null }, { "creator_type": "author", "first_name": "Ami", "last_name": "Ishii", "name": null }, { "creator_type": "author", "first_name": "Mako", "last_name": "Shiratori", "name": null }, { "creator_type": "author", "first_name": "Saki", "last_name": "Sai", "name": null }, { "creator_type": "author", "first_name": "Yuuki", "last_name": "Horii", "name": null }, { "creator_type": "author", "first_name": "Hirotaka", "last_name": "Shimizu", "name": null }, { "creator_type": "author", "first_name": "Hokuto", "last_name": "Fukumoto", "name": null }, { "creator_type": "author", "first_name": "Sumika", "last_name": "Shimba", "name": null }, { "creator_type": "author", "first_name": "Risa", "last_name": "Taguchi", "name": null }, { "creator_type": "author", "first_name": "Tadanobu", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Tadamune", "last_name": "Otsubo", "name": null }, { "creator_type": "author", "first_name": "Kiyoshi", "last_name": "Ikeda", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Suzuki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1074/jbc.m116.764357" }, "pmcid": { "normalized": "PMC5392560" }, "pmid": { "normalized": "28213516" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Brain-Derived Neurotrophic Factor", "descriptor_ui": "D019208", "major_topic": false }, { "descriptor": "CA3 Region, Hippocampal", "descriptor_ui": "D056654", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Memory", "descriptor_ui": "D008568", "major_topic": false }, { "descriptor": "N-Acetylneuraminic Acid", "descriptor_ui": "D019158", "major_topic": false }, { "descriptor": "Neuraminidase", "descriptor_ui": "D009439", "major_topic": false }, { "descriptor": "Pyramidal Cells", "descriptor_ui": "D017966", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Rats, Wistar", "descriptor_ui": "D017208", "major_topic": false }, { "descriptor": "Receptors, N-Methyl-D-Aspartate", "descriptor_ui": "D016194", "major_topic": false }, { "descriptor": "Synaptic Transmission", "descriptor_ui": "D009435", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Apr 7", "date_precision": "day", "issue": "14", "normalized_date": "2017-04-07", "pages": "5645-5654", "proceedings_title": null, "publisher": "", "title": "The Journal of biological chemistry", "volume": "292", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Rapid regulation of sialidase activity in response to neural activity and sialic acid removal during memory processing in rat hippocampus.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Fertilization calcium waves are a conserved trigger for animal development; however, genetic analysis of these waves has been limited due to the difficulty of imaging in vivo fertilization. Here we describe a protocol to image calcium dynamics during in vivo fertilization in the genetic animal model Caenorhabditis elegans. This protocol consists of germline microinjection of a chemical calcium indicator, worm immobilization, live imaging, and image processing that quantifies the calcium fluorescence in the oocyte region moving in the field-of-view during ovulation. This imaging protocol can also be used to image other cellular processes during in vivo fertilization in C. elegans, such as membrane fusion and cytoskeletal dynamics.", "classifications": [ { "id": "Onami", "label": "Group Onami", "parent": "Fujiwara", "type": "group" }, { "id": "Fujiwara", "label": "Team Fujiwara", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Jun", "last_name": "Takayama", "name": null }, { "creator_type": "author", "first_name": "Masashi", "last_name": "Fujita", "name": null }, { "creator_type": "author", "first_name": "Shuichi", "last_name": "Onami", "name": null } ], "identifiers": { "doi": { "normalized": "10.21769/bioprotoc.2205" }, "pmcid": { "normalized": "PMC8410336" }, "pmid": { "normalized": "34541214" } }, "mesh": [], "publication": { "conference_name": null, "date": "2017 Apr 5", "date_precision": "day", "issue": "7", "normalized_date": "2017-04-05", "pages": "e2205", "proceedings_title": null, "publisher": "", "title": "Bio-protocol", "volume": "7", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "In vivo Live Imaging of Calcium Waves and Other Cellular Processes during Fertilization in Caenorhabditis elegans.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "This study evaluated the clinical use of serum metabolomics to discriminate malignant cancers including pancreatic cancer (PC) from malignant diseases, such as biliary tract cancer (BTC), intraductal papillary mucinous carcinoma (IPMC), and various benign pancreaticobiliary diseases. Capillary electrophoresismass spectrometry was used to analyze charged metabolites. We repeatedly analyzed serum samples (n = 41) of different storage durations to identify metabolites showing high quantitative reproducibility, and subsequently analyzed all samples (n = 140). Overall, 189 metabolites were quantified and 66 metabolites had a 20% coefficient of variation and, of these, 24 metabolites showed significant differences among control, benign, and malignant groups (p < 0.05; Steel-Dwass test). Four multiple logistic regression models (MLR) were developed and one MLR model clearly discriminated all disease patients from healthy controls with an area under receiver operating characteristic curve (AUC) of 0.970 (95% confidential interval (CI), 0.946-0.994, p < 0.0001). Another model to discriminate PC from BTC and IPMC yielded AUC = 0.831 (95% CI, 0.650-1.01, p = 0.0020) with higher accuracy compared with tumor markers including carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9), pancreatic cancer-associated antigen (DUPAN2) and s-pancreas-1 antigen (SPAN1). Changes in metabolomic profiles might be used to screen for malignant cancers as well as to differentiate between PC and other malignant diseases.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Takao", "last_name": "Itoi", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Sugimoto", "name": null }, { "creator_type": "author", "first_name": "Junko", "last_name": "Umeda", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Sofuni", "name": null }, { "creator_type": "author", "first_name": "Takayoshi", "last_name": "Tsuchiya", "name": null }, { "creator_type": "author", "first_name": "Shujiro", "last_name": "Tsuji", "name": null }, { "creator_type": "author", "first_name": "Reina", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Ryosuke", "last_name": "Tonozuka", "name": null }, { "creator_type": "author", "first_name": "Mitsuyoshi", "last_name": "Honjo", "name": null }, { "creator_type": "author", "first_name": "Fuminori", "last_name": "Moriyasu", "name": null }, { "creator_type": "author", "first_name": "Kazuhiko", "last_name": "Kasuya", "name": null }, { "creator_type": "author", "first_name": "Yuichi", "last_name": "Nagakawa", "name": null }, { "creator_type": "author", "first_name": "Yuta", "last_name": "Abe", "name": null }, { "creator_type": "author", "first_name": "Kimihiro", "last_name": "Takano", "name": null }, { "creator_type": "author", "first_name": "Shigeyuki", "last_name": "Kawachi", "name": null }, { "creator_type": "author", "first_name": "Motohide", "last_name": "Shimazu", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Masaru", "last_name": "Tomita", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Sunamura", "name": null } ], "identifiers": { "doi": { "normalized": "10.3390/ijms18040767" }, "pmcid": { "normalized": "PMC5412351" }, "pmid": { "normalized": "28375170" } }, "mesh": [ { "descriptor": "Adenocarcinoma, Mucinous", "descriptor_ui": "D002288", "major_topic": false }, { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Aged, 80 and over", "descriptor_ui": "D000369", "major_topic": false }, { "descriptor": "Biliary Tract Neoplasms", "descriptor_ui": "D001661", "major_topic": false }, { "descriptor": "Biomarkers, Tumor", "descriptor_ui": "D014408", "major_topic": false }, { "descriptor": "Carcinoma, Pancreatic Ductal", "descriptor_ui": "D021441", "major_topic": false }, { "descriptor": "Carcinoma, Papillary", "descriptor_ui": "D002291", "major_topic": false }, { "descriptor": "Diagnosis, Differential", "descriptor_ui": "D003937", "major_topic": false }, { "descriptor": "Electrophoresis, Capillary", "descriptor_ui": "D019075", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Logistic Models", "descriptor_ui": "D016015", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mass Spectrometry", "descriptor_ui": "D013058", "major_topic": false }, { "descriptor": "Metabolomics", "descriptor_ui": "D055432", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Pancreatic Neoplasms", "descriptor_ui": "D010190", "major_topic": false }, { "descriptor": "Reproducibility of Results", "descriptor_ui": "D015203", "major_topic": false }, { "descriptor": "Sensitivity and Specificity", "descriptor_ui": "D012680", "major_topic": false }, { "descriptor": "Young Adult", "descriptor_ui": "D055815", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Apr 4", "date_precision": "day", "issue": "4", "normalized_date": "2017-04-04", "pages": "", "proceedings_title": null, "publisher": "", "title": "International journal of molecular sciences", "volume": "18", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Serum Metabolomic Profiles for Human Pancreatic Cancer Discrimination.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The H19 gene, one of the best known imprinted genes, encodes a long non-coding RNA that regulates cell proliferation and differentiation. H19 RNA is widely expressed in embryonic tissues, but its expression is restricted in only a few tissues after birth. However, regulation of H19 gene expression remains poorly understood outside the context of genomic imprinting. Here we identified evolutionarily conserved guanine (G)-rich repeated motifs at the 5' end of the H19 coding region that are consistent with theoretically deduced G-quadruplex sequences. Circular dichroism spectroscopy and electrophoretic mobility shift assays with G-quadruplex-specific ligands revealed that the G-rich motif, located immediately downstream of the transcription start site (TSS), forms a G-quadruplex structure in vitro. By using a series of mutant forms of H19 harboring deletion or G-to-A substitutions, we found that the H19-G-quadruplex regulates H19 gene expression. We further showed that transcription factors Sp1 and E2F1 were associated with the H19-G-quadruplex to either suppress or promote the H19 transcription, respectively. Moreover, H19 expression during differentiation of mouse embryonic stem cells appears to be regulated by a genomic H19 G-quadruplex. These results demonstrate that the G-quadruplex structure immediately downstream of the TSS functions as a novel regulatory element for H19 gene expression.", "classifications": [ { "id": "Toyoshima", "label": "Group Toyoshima", "parent": "Toyoshima", "type": "group" }, { "id": "Toyoshima", "label": "Team Toyoshima", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Mitsuko", "last_name": "Fukuhara", "name": null }, { "creator_type": "author", "first_name": "Yue", "last_name": "Ma", "name": null }, { "creator_type": "author", "first_name": "Kazuo", "last_name": "Nagasawa", "name": null }, { "creator_type": "author", "first_name": "Fumiko", "last_name": "Toyoshima", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/srep45815" }, "pmcid": { "normalized": "PMC5377947" }, "pmid": { "normalized": "28367967" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Circular Dichroism", "descriptor_ui": "D002942", "major_topic": false }, { "descriptor": "DNA Methylation", "descriptor_ui": "D019175", "major_topic": false }, { "descriptor": "E2F1 Transcription Factor", "descriptor_ui": "D050687", "major_topic": false }, { "descriptor": "G-Quadruplexes", "descriptor_ui": "D054856", "major_topic": true }, { "descriptor": "Gene Expression Regulation", "descriptor_ui": "D005786", "major_topic": false }, { "descriptor": "Genomic Imprinting", "descriptor_ui": "D018392", "major_topic": false }, { "descriptor": "Guanine", "descriptor_ui": "D006147", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Nucleotide Motifs", "descriptor_ui": "D059372", "major_topic": false }, { "descriptor": "Open Reading Frames", "descriptor_ui": "D016366", "major_topic": false }, { "descriptor": "Promoter Regions, Genetic", "descriptor_ui": "D011401", "major_topic": false }, { "descriptor": "RNA, Long Noncoding", "descriptor_ui": "D062085", "major_topic": false }, { "descriptor": "Sequence Deletion", "descriptor_ui": "D017384", "major_topic": false }, { "descriptor": "Sp1 Transcription Factor", "descriptor_ui": "D016329", "major_topic": false }, { "descriptor": "Transcription Initiation Site", "descriptor_ui": "D024363", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Apr 3", "date_precision": "day", "issue": "", "normalized_date": "2017-04-03", "pages": "45815", "proceedings_title": null, "publisher": "", "title": "Scientific reports", "volume": "8", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "A G-quadruplex structure at the 5' end of the H19 coding region regulates H19 transcription.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Experimental animal models have played an indispensable role in the development of human induced pluripotent stem cell (iPSC) research. The derivation of high-quality (so-called \"true naive state\") iPSCs of non-human primates enhances their application and safety for human regenerative medicine. Although several attempts have been made to convert human and non-human primate PSCs into a truly naive state, it is unclear which evaluation methods can discriminate them as being truly naive. Here we attempted to derive naive cynomolgus monkey (Cm) (Macaca fascicularis) embryonic stem cells (ESCs) and iPSCs. Several characteristics of naive Cm ESCs including colony morphology, appearance of naive-related mRNAs and proteins, leukaemia inhibitory factor dependency, and mitochondrial respiration were confirmed. Next, we generated Cm iPSCs and converted them to a naive state. Transcriptomic comparison of PSCs with early Cm embryos elucidated the partial achievement (termed naive-like) of their conversion. When these were subjected to in vitro neural differentiation, enhanced differentiating capacities were observed after naive-like conversion, but some lines exhibited heterogeneity. The difficulty of achieving contribution to chimeric mouse embryos was also demonstrated. These results suggest that Cm PSCs could ameliorate their in vitro neural differentiation potential even though they could not display true naive characteristics.", "classifications": [ { "id": "Yamamoto", "label": "Group Yamamoto", "parent": "Toyoshima", "type": "group" }, { "id": "Toyoshima", "label": "Team Toyoshima", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Arata", "last_name": "Honda", "name": null }, { "creator_type": "author", "first_name": "Yoshihiro", "last_name": "Kawano", "name": null }, { "creator_type": "author", "first_name": "Haruna", "last_name": "Izu", "name": null }, { "creator_type": "author", "first_name": "Narantsog", "last_name": "Choijookhuu", "name": null }, { "creator_type": "author", "first_name": "Kimiko", "last_name": "Honsho", "name": null }, { "creator_type": "author", "first_name": "Tomonori", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Yukihiro", "last_name": "Yabuta", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Yasuhiro", "last_name": "Takashima", "name": null }, { "creator_type": "author", "first_name": "Michiko", "last_name": "Hirose", "name": null }, { "creator_type": "author", "first_name": "Tadashi", "last_name": "Sankai", "name": null }, { "creator_type": "author", "first_name": "Yoshitaka", "last_name": "Hishikawa", "name": null }, { "creator_type": "author", "first_name": "Atsuo", "last_name": "Ogura", "name": null }, { "creator_type": "author", "first_name": "Mitinori", "last_name": "Saitou", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/srep45285" }, "pmcid": { "normalized": "PMC5368663" }, "pmid": { "normalized": "28349944" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Chimera", "descriptor_ui": "D002678", "major_topic": false }, { "descriptor": "Deoxyglucose", "descriptor_ui": "D003847", "major_topic": false }, { "descriptor": "Doxorubicin", "descriptor_ui": "D004317", "major_topic": false }, { "descriptor": "Embryonic Stem Cells", "descriptor_ui": "D053595", "major_topic": false }, { "descriptor": "Induced Pluripotent Stem Cells", "descriptor_ui": "D057026", "major_topic": false }, { "descriptor": "Leukemia Inhibitory Factor", "descriptor_ui": "D053605", "major_topic": false }, { "descriptor": "Macaca fascicularis", "descriptor_ui": "D008252", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred ICR", "descriptor_ui": "D008813", "major_topic": false }, { "descriptor": "Mitochondria", "descriptor_ui": "D008928", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Transcription Factors", "descriptor_ui": "D014157", "major_topic": false }, { "descriptor": "Transcriptome", "descriptor_ui": "D059467", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Mar 28", "date_precision": "day", "issue": "", "normalized_date": "2017-03-28", "pages": "45285", "proceedings_title": null, "publisher": "", "title": "Scientific reports", "volume": "7", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Discrimination of Stem Cell Status after Subjecting Cynomolgus Monkey Pluripotent Stem Cells to Naive Conversion.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Holometabolous insect larvae become committed to metamorphosis when they reach a critical weight. Although the physiological mechanisms involved in this process have been well-studied, the adaptive significance of the critical weight remains unclear. Here, we developed a life history model for holometabolous insects and evaluated it from the viewpoint of optimal energy allocation. We found that, without a priori assumptions about critical weight, the optimal growth schedule is always biphasic: larval tissues grow predominately until they reach a certain threshold, after which the imaginal tissues begin rapid growth, suggesting that the emergence of a critical weight as a phase-transition point is a natural consequence of optimal growth scheduling. Our model predicts the optimal timing of critical-weight attainment, in agreement with observations in phylogenetically-distinct species. Furthermore, it also predicts the scaling of growth scheduling against environmental change, i.e., the relative value and timing of the critical weight should be constant, thus providing a general interpretation of observed phenotypic plasticity. This scaling relationship allows the classification of adaptive responses in critical weight into five possible types that reflect the ecological features of focal insects. In this manner, our theory and its consistency with experimental observations demonstrate the adaptive significance of critical weight.", "classifications": [ { "id": "Morishita", "label": "Group Morishita", "parent": "Morishita", "type": "group" }, { "id": "Morishita", "label": "Team Morishita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Ken-Ichi", "last_name": "Hironaka", "name": null }, { "creator_type": "author", "first_name": "Yoshihiro", "last_name": "Morishita", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.jtbi.2017.01.014" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "28095304" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Body Weight", "descriptor_ui": "D001835", "major_topic": true }, { "descriptor": "Insecta", "descriptor_ui": "D007313", "major_topic": false }, { "descriptor": "Larva", "descriptor_ui": "D007814", "major_topic": false }, { "descriptor": "Life Cycle Stages", "descriptor_ui": "D008018", "major_topic": false }, { "descriptor": "Metamorphosis, Biological", "descriptor_ui": "D008675", "major_topic": true }, { "descriptor": "Models, Biological", "descriptor_ui": "D008954", "major_topic": true } ], "publication": { "conference_name": null, "date": "2017 Mar 21", "date_precision": "day", "issue": "", "normalized_date": "2017-03-21", "pages": "68-83", "proceedings_title": null, "publisher": "", "title": "Journal of theoretical biology", "volume": "417", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Adaptive significance of critical weight for metamorphosis in holometabolous insects.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "We previously demonstrated different spacial expression profiles of the neuronal nitric oxide (NO) synthase (nNOS) splice variants nNOS-micro and nNOS-alpha in the brain; however, their exact functions are not fully understood. Here, we used electron paramagnetic resonance to compare the electron-uncoupling reactions of recombinant nNOS-micro and nNOS-alpha that generate reactive oxygen species (ROS), in this case superoxide. nNOS-micro generated 44% of the amount of superoxide that nNOS-alpha generated. We also evaluated the ROS production in HEK293 cells stably expressing nNOS-alpha and nNOS-micro by investigating these electron-uncoupling reactions as induced by calcium ionophore A23187. A23187 treatment induced greater ROS production in HEK293 cells expressing nNOS-alpha than those expressing nNOS-micro. Also, immunocytochemical analysis revealed that A23187-treated cells expressing nNOS-alpha produced more 8-nitroguanosine 3',5'-cyclic monophosphate, a second messenger in NO/ROS redox signaling, than did the cells expressing nNOS-micro. Molecular evolutionary analysis revealed that the ratio of nonsynonymous sites to synonymous sites for the nNOS-micro-specific region was higher than that for the complete gene, indicating that this region has fewer functional constraints than does the complete gene. These observations shed light on the physiological relevance of the nNOS-micro variant and may improve understanding of nNOS-dependent NO/ROS redox signaling and its pathophysiological consequences in neuronal systems.", "classifications": [ { "id": "Akaike", "label": "Group Akaike", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Hideshi", "last_name": "Ihara", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Kitamura", "name": null }, { "creator_type": "author", "first_name": "Shingo", "last_name": "Kasamatsu", "name": null }, { "creator_type": "author", "first_name": "Tomoaki", "last_name": "Ida", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Kakihana", "name": null }, { "creator_type": "author", "first_name": "Hiroyasu", "last_name": "Tsutsuki", "name": null }, { "creator_type": "author", "first_name": "Tomohiro", "last_name": "Sawa", "name": null }, { "creator_type": "author", "first_name": "Yasuo", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Takaaki", "last_name": "Akaike", "name": null } ], "identifiers": { "doi": { "normalized": "10.1042/bcj20160999" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "28126743" } }, "mesh": [ { "descriptor": "Alternative Splicing", "descriptor_ui": "D017398", "major_topic": true }, { "descriptor": "Amino Acid Sequence", "descriptor_ui": "D000595", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Base Sequence", "descriptor_ui": "D001483", "major_topic": false }, { "descriptor": "Calcimycin", "descriptor_ui": "D000001", "major_topic": false }, { "descriptor": "Cloning, Molecular", "descriptor_ui": "D003001", "major_topic": false }, { "descriptor": "Cyclic GMP", "descriptor_ui": "D006152", "major_topic": false }, { "descriptor": "Electrons", "descriptor_ui": "D004583", "major_topic": true }, { "descriptor": "Escherichia coli", "descriptor_ui": "D004926", "major_topic": false }, { "descriptor": "Gene Expression", "descriptor_ui": "D015870", "major_topic": false }, { "descriptor": "HEK293 Cells", "descriptor_ui": "D057809", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Isoenzymes", "descriptor_ui": "D007527", "major_topic": false }, { "descriptor": "Nitric Oxide Synthase Type I", "descriptor_ui": "D052248", "major_topic": false }, { "descriptor": "Oxidation-Reduction", "descriptor_ui": "D010084", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Recombinant Proteins", "descriptor_ui": "D011994", "major_topic": false }, { "descriptor": "Sequence Alignment", "descriptor_ui": "D016415", "major_topic": false }, { "descriptor": "Superoxides", "descriptor_ui": "D013481", "major_topic": false }, { "descriptor": "Transfection", "descriptor_ui": "D014162", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Mar 15", "date_precision": "day", "issue": "7", "normalized_date": "2017-03-15", "pages": "1149-1162", "proceedings_title": null, "publisher": "", "title": "The Biochemical journal", "volume": "474", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Superoxide generation from nNOS splice variants and its potential involvement in redox signal regulation.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Slight changes in the coordination structure of the manganese(v)-nitrido anionic complex, [Mn(V)(N)(CN)(4)](2-), induced by using a \"lipid package\" approach markedly made an impact on the corresponding redox potentials. The single crystals of four lipid assemblies, [dabco-(CH(2))(n-1)-CH(3)](2)[Mn(N)(CN)(4)(H(2)O)].xH(2)O (n = 15, 16, 17 and 18; dabco = 1,4-diazabicyclo[2,2,2]octane), were synthesized and solid-state cyclic voltammetric studies demonstrated that the [Mn(V)(N)(CN)(4)](2-) anions with smaller \"cross\" NC-Mn-CN bond angles exhibit higher redox potentials. The observed trend reflects the energy change associated with the structural transformation from [Mn(V)(N)(CN)(4)](2-) to [Mn(VI)(N)(CN)(4)](2-) and is supported by the results of DFT calculations. The NC-Mn-CN bond angles in the flexible [Mn(N)(CN)(4)](2-) structure exhibit excellent correlation with the redox potentials of the complexes in the solid state.", "classifications": [ { "id": "Hijikata", "label": "Group Hijikata", "parent": "Tsuchiya", "type": "group" }, { "id": "Tsuchiya", "label": "Team Tsuchiya", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Ryo", "last_name": "Ohtani", "name": null }, { "creator_type": "author", "first_name": "Yuu", "last_name": "Kitamura", "name": null }, { "creator_type": "author", "first_name": "Yuh", "last_name": "Hijikata", "name": null }, { "creator_type": "author", "first_name": "Masaaki", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Leonard F.", "last_name": "Lindoy", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Hayami", "name": null } ], "identifiers": { "doi": { "normalized": "10.1039/c7dt00233e" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "28262891" } }, "mesh": [], "publication": { "conference_name": null, "date": "2017 Mar 14", "date_precision": "day", "issue": "11", "normalized_date": "2017-03-14", "pages": "3749-3754", "proceedings_title": null, "publisher": "", "title": "Dalton transactions (Cambridge, England : 2003)", "volume": "46", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Modulation of redox potentials utilizing the flexible coordination sphere of a penta-coordinate complex in the solid state.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Toll-like receptor 4 (TLR4) plays an essential role in innate immunity through inflammatory cytokine induction. Recent studies demonstrated that the abnormal activation of TLR4 has a pivotal role in obesity-induced inflammation, which is associated with several diseases, including hyperinsulinemia, hypertriglyceridemia, and cardiovascular disease. Here we demonstrate that (-)-epigallocatechin-3-O-gallate, a natural agonist of the 67-kDa laminin receptor (67LR), suppressed TLR4 expression through E3 ubiquitin-protein ring finger protein 216 (RNF216) up-regulation. Our data indicate cyclic GMP mediates 67LR agonist-dependent RNF216 up-regulation. Moreover, we show that the highly absorbent 67LR agonist (-)-epigallocatechin-3-O-(3-O-methyl)-gallate (EGCG3″Me) significantly attenuated TLR4 expression in the adipose tissue. EGCG3″Me completely inhibited the high-fat/high-sucrose (HF/HS)-induced up-regulation of tumor necrosis factor α in adipose tissue and serum monocyte chemoattractant protein-1 increase. Furthermore, this agonist intake prevented HF/HS-induced hyperinsulinemia and hypertriglyceridemia. Taken together, 67LR presents an attractive target for the relief of obesity-induced inflammation.", "classifications": [ { "id": "Suzuki", "label": "Group Suzuki", "parent": "Takekawa", "type": "group" }, { "id": "Takekawa", "label": "Team Takekawa", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Motofumi", "last_name": "Kumazoe", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Mai", "last_name": "Yamashita", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Kanako", "last_name": "Takamatsu", "name": null }, { "creator_type": "author", "first_name": "Yuhui", "last_name": "Huang", "name": null }, { "creator_type": "author", "first_name": "Jaehoon", "last_name": "Bae", "name": null }, { "creator_type": "author", "first_name": "Shuya", "last_name": "Yamashita", "name": null }, { "creator_type": "author", "first_name": "Motoki", "last_name": "Murata", "name": null }, { "creator_type": "author", "first_name": "Shuhei", "last_name": "Yamada", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Shinoda", "name": null }, { "creator_type": "author", "first_name": "Wataru", "last_name": "Yamaguchi", "name": null }, { "creator_type": "author", "first_name": "Yui", "last_name": "Toyoda", "name": null }, { "creator_type": "author", "first_name": "Hirofumi", "last_name": "Tachibana", "name": null } ], "identifiers": { "doi": { "normalized": "10.1074/jbc.m116.755959" }, "pmcid": { "normalized": "PMC5354502" }, "pmid": { "normalized": "28154178" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Catechin", "descriptor_ui": "D002392", "major_topic": false }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Gene Expression Regulation", "descriptor_ui": "D005786", "major_topic": false }, { "descriptor": "Hyperinsulinism", "descriptor_ui": "D006946", "major_topic": false }, { "descriptor": "Hypertriglyceridemia", "descriptor_ui": "D015228", "major_topic": false }, { "descriptor": "Inflammation", "descriptor_ui": "D007249", "major_topic": false }, { "descriptor": "Lipopolysaccharides", "descriptor_ui": "D008070", "major_topic": false }, { "descriptor": "Macrophages, Peritoneal", "descriptor_ui": "D017737", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "NF-kappa B", "descriptor_ui": "D016328", "major_topic": false }, { "descriptor": "Obesity", "descriptor_ui": "D009765", "major_topic": false }, { "descriptor": "Receptors, Laminin", "descriptor_ui": "D017474", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Tea", "descriptor_ui": "D013662", "major_topic": false }, { "descriptor": "Toll-Like Receptor 4", "descriptor_ui": "D051197", "major_topic": false }, { "descriptor": "Transcriptional Activation", "descriptor_ui": "D015533", "major_topic": false }, { "descriptor": "Tumor Necrosis Factor-alpha", "descriptor_ui": "D014409", "major_topic": false }, { "descriptor": "Ubiquitin-Protein Ligases", "descriptor_ui": "D044767", "major_topic": false }, { "descriptor": "Up-Regulation", "descriptor_ui": "D015854", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Mar 10", "date_precision": "day", "issue": "10", "normalized_date": "2017-03-10", "pages": "4077-4088", "proceedings_title": null, "publisher": "", "title": "The Journal of biological chemistry", "volume": "292", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Green Tea Polyphenol Epigallocatechin-3-gallate Suppresses Toll-like Receptor 4 Expression via Up-regulation of E3 Ubiquitin-protein Ligase RNF216.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The new covalent organic framework material TDFP-1 was prepared through a solvothermal Schiff base condensation reaction of the monomers 1,3,5-tris-(4-aminophenyl)triazine and 2,6-diformyl-4-methylphenol. Owing to its high specific surface area of 651 m(2) g(-1) , extended pi conjugation, and inherent microporosity, TDFP-1 exhibited an excellent energy-storage capacity with a maximum specific capacitance of 354 F g(-1) at a scan rate of 2 mV s(-1) and good cyclic stability with 95 % retention of its initial specific capacitance after 1000 cycles at 10 A g(-1) . The pi-conjugated polymeric framework as well as ionic conductivity owing to the possibility of ion conduction inside the micropores of approximately 1.5 nm make polymeric TDFP-1 a favorable candidate as a supercapacitor electrode material. The electrochemical properties of this electrode material were measured through cyclic voltammetry, galvanic charge-discharge, and electrochemical impedance spectroscopy, and the results indicate its potential for application in energy-storage devices.", "classifications": [ { "id": "Hijikata", "label": "Group Hijikata", "parent": "Tsuchiya", "type": "group" }, { "id": "Tsuchiya", "label": "Team Tsuchiya", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Piyali", "last_name": "Bhanja", "name": null }, { "creator_type": "author", "first_name": "Kousik", "last_name": "Bhunia", "name": null }, { "creator_type": "author", "first_name": "Sabuj K.", "last_name": "Das", "name": null }, { "creator_type": "author", "first_name": "Debabrata", "last_name": "Pradhan", "name": null }, { "creator_type": "author", "first_name": "Ryuto", "last_name": "Kimura", "name": null }, { "creator_type": "author", "first_name": "Yuh", "last_name": "Hijikata", "name": null }, { "creator_type": "author", "first_name": "Stephan", "last_name": "Irle", "name": null }, { "creator_type": "author", "first_name": "Asim", "last_name": "Bhaumik", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/cssc.201601571" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "28058807" } }, "mesh": [ { "descriptor": "Cresols", "descriptor_ui": "D003408", "major_topic": false }, { "descriptor": "Electric Capacitance", "descriptor_ui": "D025802", "major_topic": true }, { "descriptor": "Electrochemistry", "descriptor_ui": "D004563", "major_topic": false }, { "descriptor": "Models, Molecular", "descriptor_ui": "D008958", "major_topic": false }, { "descriptor": "Molecular Conformation", "descriptor_ui": "D008968", "major_topic": false }, { "descriptor": "Schiff Bases", "descriptor_ui": "D012545", "major_topic": false }, { "descriptor": "Solvents", "descriptor_ui": "D012997", "major_topic": false }, { "descriptor": "Temperature", "descriptor_ui": "D013696", "major_topic": false }, { "descriptor": "Triazines", "descriptor_ui": "D014227", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Mar 9", "date_precision": "day", "issue": "5", "normalized_date": "2017-03-09", "pages": "921-929", "proceedings_title": null, "publisher": "", "title": "ChemSusChem", "volume": "10", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "A New Triazine-Based Covalent Organic Framework for High-Performance Capacitive Energy Storage.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "In developed countries, the number of patients with colorectal cancer has been increasing, and colorectal cancer is one of the most common causes of cancer death. To improve the quality of life of colorectal cancer patients, it is necessary to establish novel screening methods that would allow early detection of colorectal cancer. We performed metabolome analysis of a plasma sample set from 282 stage 0/I/II colorectal cancer patients and 291 healthy volunteers using gas chromatography/triple-quadrupole mass spectrometry in an attempt to identify metabolite biomarkers of stage 0/I/II colorectal cancer. The colorectal cancer patients included patients with stage 0 (N=79), I (N=80), and II (N=123) in whom invasion and metastasis were absent. Our analytical system detected 64 metabolites in the plasma samples, and the levels of 29 metabolites differed significantly (Bonferroni-corrected p=0.000781) between the patients and healthy volunteers. Based on these results, a multiple logistic regression analysis of various metabolite biomarkers was carried out, and a stage 0/I/II colorectal cancer prediction model was established. The area under the curve, sensitivity, and specificity values of this model for detecting stage 0/I/II colorectal cancer were 0.996, 99.3%, and 93.8%, respectively. The model's sensitivity and specificity values for each disease stage were >90%, and surprisingly, its sensitivity for stage 0, specificity for stage 0, and sensitivity for stage II disease were all 100%. Our predictive model can aid early detection of colorectal cancer and has potential as a novel screening test for cases of colorectal cancer that do not involve lymph node or distant metastasis.", "classifications": [ { "id": "Okamoto", "label": "Group Okamoto", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Shin", "last_name": "Nishiumi", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Shuichi", "last_name": "Kawana", "name": null }, { "creator_type": "author", "first_name": "Yumi", "last_name": "Unno", "name": null }, { "creator_type": "author", "first_name": "Takero", "last_name": "Sakai", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Okamoto", "name": null }, { "creator_type": "author", "first_name": "Yasuhide", "last_name": "Yamada", "name": null }, { "creator_type": "author", "first_name": "Kazuki", "last_name": "Sudo", "name": null }, { "creator_type": "author", "first_name": "Taiki", "last_name": "Yamaji", "name": null }, { "creator_type": "author", "first_name": "Yutaka", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Yukihide", "last_name": "Kanemitsu", "name": null }, { "creator_type": "author", "first_name": "Natsuko Tsuda", "last_name": "Okita", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Shoichiro", "last_name": "Tsugane", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Azuma", "name": null }, { "creator_type": "author", "first_name": "Noriyuki", "last_name": "Ojima", "name": null }, { "creator_type": "author", "first_name": "Masaru", "last_name": "Yoshida", "name": null } ], "identifiers": { "doi": { "normalized": "10.18632/oncotarget.15081" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "28179577" } }, "mesh": [ { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Aged, 80 and over", "descriptor_ui": "D000369", "major_topic": false }, { "descriptor": "Biomarkers, Tumor", "descriptor_ui": "D014408", "major_topic": false }, { "descriptor": "Colorectal Neoplasms", "descriptor_ui": "D015179", "major_topic": false }, { "descriptor": "Early Detection of Cancer", "descriptor_ui": "D055088", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Gas Chromatography-Mass Spectrometry", "descriptor_ui": "D008401", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Logistic Models", "descriptor_ui": "D016015", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Metabolome", "descriptor_ui": "D055442", "major_topic": true }, { "descriptor": "Metabolomics", "descriptor_ui": "D055432", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Reproducibility of Results", "descriptor_ui": "D015203", "major_topic": false }, { "descriptor": "ROC Curve", "descriptor_ui": "D012372", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Mar 7", "date_precision": "day", "issue": "10", "normalized_date": "2017-03-07", "pages": "17115-17126", "proceedings_title": null, "publisher": "", "title": "Oncotarget", "volume": "8", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Investigations in the possibility of early detection of colorectal cancer by gas chromatography/triple-quadrupole mass spectrometry.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Tension-induced exposure of a cryptic signaling binding site is one of the most fundamental mechanisms in molecular mechanotransduction. Helix bundles in rod domains of talin, a tension-sensing protein at focal adhesions, unfurl under tension to expose cryptic vinculin binding sites. Although the difference in their mechanical stabilities would determine which helix bundle is tension-sensitive, their respective mechanical behaviors under tension have not been characterized. In this study, we evaluated the mechanical behaviors of residues 486-654 and 754-889 of talin, which form helix bundles with low and high tension-sensitivity, by employing AFM nano-tensile testing. As a result, residues 754-889 exhibited lower unfolding energy for complete unfolding than residues 486-654. In addition, we found that residues 754-889 transition into intermediate conformations under lower tension than residues 486-654. Furthermore, residues 754-889 showed shorter persistence length in the intermediate conformation than residues 486-654, suggesting that residues 754-889 under tension exhibit separated alpha-helices, while residues 486-654 assume a compact conformation with inter-helix interactions. Therefore, we suggest that residues 754-889 of talin work as a tension-sensitive domain to recruit vinculin at the early stage of focal adhesion development, while residues 486-654 contribute to rather robust tension-sensitivity by recruiting vinculin under high tension.", "classifications": [ { "id": "Maki", "label": "Group Maki", "parent": "Toyoshima", "type": "group" }, { "id": "Toyoshima", "label": "Team Toyoshima", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Koichiro", "last_name": "Maki", "name": null }, { "creator_type": "author", "first_name": "Nobuhiko", "last_name": "Nakao", "name": null }, { "creator_type": "author", "first_name": "Taiji", "last_name": "Adachi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.bbrc.2017.01.127" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "28131835" } }, "mesh": [ { "descriptor": "Microscopy, Atomic Force", "descriptor_ui": "D018625", "major_topic": false }, { "descriptor": "Nanotechnology", "descriptor_ui": "D036103", "major_topic": true }, { "descriptor": "Protein Conformation", "descriptor_ui": "D011487", "major_topic": false }, { "descriptor": "Talin", "descriptor_ui": "D016608", "major_topic": false }, { "descriptor": "Tensile Strength", "descriptor_ui": "D013718", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Mar 4", "date_precision": "day", "issue": "2", "normalized_date": "2017-03-04", "pages": "372-377", "proceedings_title": null, "publisher": "", "title": "Biochemical and biophysical research communications", "volume": "484", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Nano-mechanical characterization of tension-sensitive helix bundles in talin rod.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "One major concern over the clinical application of embryonic stem cell (ESC)-derived cells is the potentiation of latent tumorigenicity by residual undifferentiated cells. Despite the use of intensive methodological approaches to eliminate residual undifferentiated cells, the properties of these cells remain elusive. Here, we show that under a serum-free neural differentiation condition, residual undifferentiated cells markedly delay progression of their cell cycle without compromising their pluripotency. This dormant pluripotency was maintained during reculture of the cells under a serum-free condition, whereas upon serum stimulation, the cells exited the dormant state and restarted proliferation and differentiation into all three germ layers. Microarray analysis revealed a set of genes that is significantly upregulated in the dormant ESCs compared with their levels of regulation in proliferating ESCs. Among them, we identified the transcription factor Forkhead box O3 (FoxO3) to be an essential regulator of the maintenance of pluripotency in dormant ESCs. Our study demonstrates that the transition into the dormant state endows residual undifferentiated cells with FoxO3-dependent and leukemia inhibitory factor/serum-independent pluripotency.", "classifications": [ { "id": "Toyoshima", "label": "Group Toyoshima", "parent": "Toyoshima", "type": "group" }, { "id": "Toyoshima", "label": "Team Toyoshima", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Megumi", "last_name": "Ikeda", "name": null }, { "creator_type": "author", "first_name": "Fumiko", "last_name": "Toyoshima", "name": null } ], "identifiers": { "doi": { "normalized": "10.1128/mcb.00417-16" }, "pmcid": { "normalized": "PMC5311243" }, "pmid": { "normalized": "27956699" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Culture Techniques", "descriptor_ui": "D018929", "major_topic": false }, { "descriptor": "Cell Cycle Checkpoints", "descriptor_ui": "D059447", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": true }, { "descriptor": "Cell Self Renewal", "descriptor_ui": "D000066673", "major_topic": false }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Forkhead Box Protein O3", "descriptor_ui": "D000071316", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mouse Embryonic Stem Cells", "descriptor_ui": "D000066450", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Octamer Transcription Factor-3", "descriptor_ui": "D050814", "major_topic": false }, { "descriptor": "Quinolones", "descriptor_ui": "D015363", "major_topic": false }, { "descriptor": "Up-Regulation", "descriptor_ui": "D015854", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Mar 1", "date_precision": "day", "issue": "5", "normalized_date": "2017-03-01", "pages": "e00417-16", "proceedings_title": null, "publisher": "", "title": "Molecular and cellular biology", "volume": "37", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Dormant Pluripotent Cells Emerge during Neural Differentiation of Embryonic Stem Cells in a FoxO3-Dependent Manner.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Why is the spine of a neuron so small that it can contain only small numbers of molecules and reactions inevitably become stochastic? We previously showed that, despite such noisy conditions, the spine exhibits robust, sensitive, and efficient features of information transfer using the probability of Ca(2+) increase; however, the mechanisms are unknown. In this study, we show that the small volume effect enables robust, sensitive, and efficient information transfer in the spine volume, but not in the cell volume. In the spine volume, the intrinsic noise in reactions becomes larger than the extrinsic noise of input, resulting in robust information transfer despite input fluctuation. In the spine volume, stochasticity makes the Ca(2+) increase occur with a lower intensity of input, causing higher sensitivity to lower intensity of input. The volume-dependency of information transfer increases its efficiency in the spine volume. Thus, we propose that the small-volume effect is the functional reason why the spine has to be so small.", "classifications": [ { "id": "Kuroda", "label": "Group Kuroda", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Masashi", "last_name": "Fujii", "name": null }, { "creator_type": "author", "first_name": "Kaoru", "last_name": "Ohashi", "name": null }, { "creator_type": "author", "first_name": "Yasuaki", "last_name": "Karasawa", "name": null }, { "creator_type": "author", "first_name": "Minori", "last_name": "Hikichi", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Kuroda", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.bpj.2016.12.043" }, "pmcid": { "normalized": "PMC5340173" }, "pmid": { "normalized": "28256240" } }, "mesh": [ { "descriptor": "Calcium", "descriptor_ui": "D002118", "major_topic": false }, { "descriptor": "Dendritic Spines", "descriptor_ui": "D049229", "major_topic": false }, { "descriptor": "Models, Neurological", "descriptor_ui": "D008959", "major_topic": true }, { "descriptor": "Purkinje Cells", "descriptor_ui": "D011689", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Stochastic Processes", "descriptor_ui": "D013269", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Feb 28", "date_precision": "day", "issue": "4", "normalized_date": "2017-02-28", "pages": "813-826", "proceedings_title": null, "publisher": "", "title": "Biophysical journal", "volume": "112", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Small-Volume Effect Enables Robust, Sensitive, and Efficient Information Transfer in the Spine.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Hereditary motor and sensory neuropathy with proximal dominant involvement (HMSN-P) is caused by a heterozygous mutation (P285L) in Tropomyosin-receptor kinase Fused Gene (TFG), histopathologically characterized by progressive spinal motor neuron loss with TFG cytosolic aggregates. Although the TFG protein, found as a type of fusion oncoprotein, is known to facilitate vesicle transport from endoplasmic reticulum (ER) to Golgi apparatus at ER exit site, it is unclear how mutant TFG causes motor neuron degeneration. Here we generated induced pluripotent stem cells (iPSCs) from HMSN-P patients, and differentiated the iPSCs into neural cells with spinal motor neurons (iPS-MNs). We found that HMSN-P patient iPS-MNs exhibited ubiquitin proteasome system (UPS) impairment, and HMSN-P patient iPS-MNs were vulnerable to UPS inhibitory stress. Gene correction of the mutation in TFG using the CRISPR-Cas9 system reverted the cellular phenotypes of HMSN-P patient iPS-MNs. Collectively, these results suggest that our cellular model with defects in cellular integrity including UPS impairments may lead to identification of pathomechanisms and a therapeutic target for HMSN-P.", "classifications": [ { "id": "Yamamoto", "label": "Group Yamamoto", "parent": "Toyoshima", "type": "group" }, { "id": "Toyoshima", "label": "Team Toyoshima", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Nagahisa", "last_name": "Murakami", "name": null }, { "creator_type": "author", "first_name": "Keiko", "last_name": "Imamura", "name": null }, { "creator_type": "author", "first_name": "Yuishin", "last_name": "Izumi", "name": null }, { "creator_type": "author", "first_name": "Naohiro", "last_name": "Egawa", "name": null }, { "creator_type": "author", "first_name": "Kayoko", "last_name": "Tsukita", "name": null }, { "creator_type": "author", "first_name": "Takako", "last_name": "Enami", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Toshitaka", "last_name": "Kawarai", "name": null }, { "creator_type": "author", "first_name": "Ryuji", "last_name": "Kaji", "name": null }, { "creator_type": "author", "first_name": "Haruhisa", "last_name": "Inoue", "name": null } ], "identifiers": { "doi": { "normalized": "10.1186/s13041-017-0286-y" }, "pmcid": { "normalized": "PMC5310050" }, "pmid": { "normalized": "28196470" } }, "mesh": [ { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Aged, 80 and over", "descriptor_ui": "D000369", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Clone Cells", "descriptor_ui": "D002999", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Hereditary Sensory and Motor Neuropathy", "descriptor_ui": "D015417", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Induced Pluripotent Stem Cells", "descriptor_ui": "D057026", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Motor Neurons", "descriptor_ui": "D009046", "major_topic": false }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Phenotype", "descriptor_ui": "D010641", "major_topic": false }, { "descriptor": "Proteasome Endopeptidase Complex", "descriptor_ui": "D046988", "major_topic": false }, { "descriptor": "Proteins", "descriptor_ui": "D011506", "major_topic": false }, { "descriptor": "Spinal Cord", "descriptor_ui": "D013116", "major_topic": false }, { "descriptor": "Vesicular Transport Proteins", "descriptor_ui": "D033921", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Feb 15", "date_precision": "day", "issue": "1", "normalized_date": "2017-02-15", "pages": "7", "proceedings_title": null, "publisher": "", "title": "Molecular brain", "volume": "10", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Proteasome impairment in neural cells derived from HMSN-P patient iPSCs.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: Recent studies have shown that plasma levels of the biologically inactive prohormone for brain natriuretic peptide (proBNP) are increased in patients with heart failure. This can contribute to a reduction in the effectiveness of circulating BNP and exacerbate heart failure progression. The precise mechanisms governing the increase in proBNP remain unclear, however. METHODS AND RESULTS: We used our recently developed, highly sensitive human proBNP assay system to investigate the mechanisms underlying the increase in plasma proBNP levels. We divided 53 consecutive patients hospitalized with heart failure into 2 groups based on their aortic plasma levels of immunoreactive BNP. Patients with higher levels exhibited more severe heart failure, a higher proportion of proBNP among the immunoreactive BNP forms secreted from failing hearts, and a weaker effect of BNP as estimated from the ratio of plasma cyclic guanosine monophosphate levels to log-transformed plasma BNP levels. Glycosylation at threonines 48 and 71 of human proBNP contributed to the increased secretion of proBNP by attenuating its processing, and GalNAc-transferase (GALNT) 1 and 2 mediated the glycosylation-regulated increase in cardiac human proBNP secretion. Cardiac GALNT1 and 2 expression was suppressed by microRNA (miR)-30, which is abundantly expressed in the myocardium of healthy hearts, but is suppressed in failing hearts. CONCLUSIONS: We have elucidated a novel miR-30-GALNT1/2 axis whose dysregulation increases the proportion of inactive proBNP secreted by the heart and impairs the compensatory actions of BNP during the progression of heart failure.", "classifications": [ { "id": "Nishida", "label": "Group Nishida", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yasuaki", "last_name": "Nakagawa", "name": null }, { "creator_type": "author", "first_name": "Toshio", "last_name": "Nishikimi", "name": null }, { "creator_type": "author", "first_name": "Koichiro", "last_name": "Kuwahara", "name": null }, { "creator_type": "author", "first_name": "Aoi", "last_name": "Fujishima", "name": null }, { "creator_type": "author", "first_name": "Shogo", "last_name": "Oka", "name": null }, { "creator_type": "author", "first_name": "Takayoshi", "last_name": "Tsutamoto", "name": null }, { "creator_type": "author", "first_name": "Hideyuki", "last_name": "Kinoshita", "name": null }, { "creator_type": "author", "first_name": "Kazuhiro", "last_name": "Nakao", "name": null }, { "creator_type": "author", "first_name": "Kosai", "last_name": "Cho", "name": null }, { "creator_type": "author", "first_name": "Hideaki", "last_name": "Inazumi", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Okamoto", "name": null }, { "creator_type": "author", "first_name": "Motohiro", "last_name": "Nishida", "name": null }, { "creator_type": "author", "first_name": "Takao", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Fukushima", "name": null }, { "creator_type": "author", "first_name": "Jun K.", "last_name": "Yamashita", "name": null }, { "creator_type": "author", "first_name": "Wino J.", "last_name": "Wijnen", "name": null }, { "creator_type": "author", "first_name": "Esther E.", "last_name": "Creemers", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Kangawa", "name": null }, { "creator_type": "author", "first_name": "Naoto", "last_name": "Minamino", "name": null }, { "creator_type": "author", "first_name": "Kazuwa", "last_name": "Nakao", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Kimura", "name": null } ], "identifiers": { "doi": { "normalized": "10.1161/jaha.116.003601" }, "pmcid": { "normalized": "PMC5523735" }, "pmid": { "normalized": "28188250" } }, "mesh": [ { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Animals, Newborn", "descriptor_ui": "D000831", "major_topic": false }, { "descriptor": "Aorta, Thoracic", "descriptor_ui": "D001013", "major_topic": false }, { "descriptor": "Biomarkers", "descriptor_ui": "D015415", "major_topic": false }, { "descriptor": "Blotting, Western", "descriptor_ui": "D015153", "major_topic": false }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Chromatography, Gel", "descriptor_ui": "D002850", "major_topic": false }, { "descriptor": "Disease Models, Animal", "descriptor_ui": "D004195", "major_topic": false }, { "descriptor": "Disease Progression", "descriptor_ui": "D018450", "major_topic": false }, { "descriptor": "Echocardiography", "descriptor_ui": "D004452", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Follow-Up Studies", "descriptor_ui": "D005500", "major_topic": false }, { "descriptor": "Gene Expression Regulation", "descriptor_ui": "D005786", "major_topic": true }, { "descriptor": "Glycosylation", "descriptor_ui": "D006031", "major_topic": false }, { "descriptor": "Heart Failure", "descriptor_ui": "D006333", "major_topic": false }, { "descriptor": "Heart Ventricles", "descriptor_ui": "D006352", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "MicroRNAs", "descriptor_ui": "D035683", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Myocardium", "descriptor_ui": "D009206", "major_topic": false }, { "descriptor": "Myocytes, Cardiac", "descriptor_ui": "D032383", "major_topic": false }, { "descriptor": "N-Acetylgalactosaminyltransferases", "descriptor_ui": "D017350", "major_topic": false }, { "descriptor": "Natriuretic Peptide, Brain", "descriptor_ui": "D020097", "major_topic": false }, { "descriptor": "Peptide Fragments", "descriptor_ui": "D010446", "major_topic": false }, { "descriptor": "Polypeptide N-acetylgalactosaminyltransferase", "descriptor_ui": "D000097763", "major_topic": false }, { "descriptor": "Protein Precursors", "descriptor_ui": "D011498", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Rats, Inbred Dahl", "descriptor_ui": "D020303", "major_topic": false }, { "descriptor": "Real-Time Polymerase Chain Reaction", "descriptor_ui": "D060888", "major_topic": false }, { "descriptor": "Retrospective Studies", "descriptor_ui": "D012189", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Feb 10", "date_precision": "day", "issue": "2", "normalized_date": "2017-02-10", "pages": "", "proceedings_title": null, "publisher": "", "title": "Journal of the American Heart Association", "volume": "6", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "MiR30-GALNT1/2 Axis-Mediated Glycosylation Contributes to the Increased Secretion of Inactive Human Prohormone for Brain Natriuretic Peptide (proBNP) From Failing Hearts.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "We investigate the metabolomic profile of reactive persulfides and polysulfides in the aqueous and vitreous humors. Eighteen eyes of 18 consecutive patients with diabetes mellitus (DM) and diabetic retinopathy underwent microincision vitrectomy combined with cataract surgery. Samples of the aqueous and vitreous humors were collected and underwent mass spectrometry-based metabolomic profiling of reactive persulfides and polysulfides (polysulfidomics). The effect of reactive polysulfide species on the viability of immortalized retinal cells (the RGC-5 cell line) under oxidative stress (induced with H(2)O(2)) was also evaluated with an Alamar Blue assay. The experiments showed that cysteine persulfides (CysSSH), oxidized glutathione trisulfide (GSSSG) and cystine were elevated in the aqueous humor, and CysSSH, Cys, and cystine were elevated in the vitreous. Furthermore, GSSSG, cystine, and CysSSH levels were correlated in the aqueous and vitreous humors. A comparison, in DM and control subjects, of plasma levels of reactive persulfides and polysulfides showed that they did not differ. In vitro findings revealed that reactive polysulfide species increased cell viability under oxidative stress. Thus, various reactive persulfides and polysulfides appear to be present in the eye, and some reactive sulfide species, which have a protective effect against oxidative stress, are upregulated in the aqueous and vitreous humors of DM eyes.", "classifications": [ { "id": "Akaike", "label": "Group Akaike", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Kunikata", "name": null }, { "creator_type": "author", "first_name": "Tomoaki", "last_name": "Ida", "name": null }, { "creator_type": "author", "first_name": "Kota", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Naoko", "last_name": "Aizawa", "name": null }, { "creator_type": "author", "first_name": "Tomohiro", "last_name": "Sawa", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Tawarayama", "name": null }, { "creator_type": "author", "first_name": "Namie", "last_name": "Murayama", "name": null }, { "creator_type": "author", "first_name": "Shigemoto", "last_name": "Fujii", "name": null }, { "creator_type": "author", "first_name": "Takaaki", "last_name": "Akaike", "name": null }, { "creator_type": "author", "first_name": "Toru", "last_name": "Nakazawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/srep41984" }, "pmcid": { "normalized": "PMC5294455" }, "pmid": { "normalized": "28169324" } }, "mesh": [ { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Aged, 80 and over", "descriptor_ui": "D000369", "major_topic": false }, { "descriptor": "Aqueous Humor", "descriptor_ui": "D001082", "major_topic": false }, { "descriptor": "Case-Control Studies", "descriptor_ui": "D016022", "major_topic": false }, { "descriptor": "Diabetes Mellitus", "descriptor_ui": "D003920", "major_topic": false }, { "descriptor": "Diabetic Retinopathy", "descriptor_ui": "D003930", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Metabolomics", "descriptor_ui": "D055432", "major_topic": true }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Oxidation-Reduction", "descriptor_ui": "D010084", "major_topic": false }, { "descriptor": "Retrospective Studies", "descriptor_ui": "D012189", "major_topic": false }, { "descriptor": "Sulfides", "descriptor_ui": "D013440", "major_topic": false }, { "descriptor": "Vitrectomy", "descriptor_ui": "D014821", "major_topic": false }, { "descriptor": "Vitreous Body", "descriptor_ui": "D014822", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Feb 7", "date_precision": "day", "issue": "", "normalized_date": "2017-02-07", "pages": "41984", "proceedings_title": null, "publisher": "", "title": "Scientific reports", "volume": "7", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Metabolomic profiling of reactive persulfides and polysulfides in the aqueous and vitreous humors.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Organoids mimicking the formation of the brain cortex have been demonstrated to be powerful tools for developmental studies as well as pathological investigations of brain malformations. Here, we report an integrated approach for the quantification of temporal neural production (neurogenic rate) in organoids derived from embryonic brains. Spherical tissue fragments with polarized cytoarchitectures were incubated in multiple cavities arranged in a polymethylmethacrylate chip. The time-dependent neurogenic rate in the organoids was monitored by the level of EGFP under the promoter of Tbr2, a transcription factor that is transiently expressed in neural fate-committed progenitors during corticogenesis. Importantly, our monitoring system exhibited a quick response to DAPT, a drug that promotes neural differentiation. Furthermore, we successfully quantified the temporal neurogenic rate in a large number of organoids by applying image processing that semi-automatically recognized the positions of organoids and measured their signal intensities from sequential images. Taken together, we provide a strategy to quantitate the neurogenic rate in brain organoids in a time-dependent manner, which will also be a potent method for monitoring organoid formation and drug activity in other tissue types.", "classifications": [ { "id": "Kobayashi", "label": "Group Kobayashi", "parent": "Wakamoto", "type": "group" }, { "id": "Wakamoto", "label": "Team Wakamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yoichi", "last_name": "Kosodo", "name": null }, { "creator_type": "author", "first_name": "Taeko", "last_name": "Suetsugu", "name": null }, { "creator_type": "author", "first_name": "Tetsuya J.", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Fumio", "last_name": "Matsuzaki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.bbrc.2016.12.187" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "28063930" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Brain", "descriptor_ui": "D001921", "major_topic": false }, { "descriptor": "Cerebral Cortex", "descriptor_ui": "D002540", "major_topic": false }, { "descriptor": "Embryonic Stem Cells", "descriptor_ui": "D053595", "major_topic": false }, { "descriptor": "Green Fluorescent Proteins", "descriptor_ui": "D049452", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Transgenic", "descriptor_ui": "D008822", "major_topic": false }, { "descriptor": "Neural Stem Cells", "descriptor_ui": "D058953", "major_topic": false }, { "descriptor": "Neurogenesis", "descriptor_ui": "D055495", "major_topic": false }, { "descriptor": "Organ Culture Techniques", "descriptor_ui": "D009924", "major_topic": false }, { "descriptor": "Organoids", "descriptor_ui": "D009940", "major_topic": false }, { "descriptor": "Time-Lapse Imaging", "descriptor_ui": "D059008", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Jan 29", "date_precision": "day", "issue": "1", "normalized_date": "2017-01-29", "pages": "94-100", "proceedings_title": null, "publisher": "", "title": "Biochemical and biophysical research communications", "volume": "483", "year": 2017 }, "ssbd": { "database": [ "ssbd-database-000085" ], "repository": [ "ssbd-repos-000085" ] }, "title": "Systematic time-dependent visualization and quantitation of the neurogenic rate in brain organoids.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Both land plants and metazoa have the capacity to reprogram differentiated cells to stem cells. Here we show that the moss Physcomitrella patens Cold-Shock Domain Protein 1 (PpCSP1) regulates reprogramming of differentiated leaf cells to chloronema apical stem cells and shares conserved domains with the induced pluripotent stem cell factor Lin28 in mammals. PpCSP1 accumulates in the reprogramming cells and is maintained throughout the reprogramming process and in the resultant stem cells. Expression of PpCSP1 is negatively regulated by its 3'-untranslated region (3'-UTR). Removal of the 3'-UTR stabilizes PpCSP1 transcripts, results in accumulation of PpCSP1 protein and enhances reprogramming. A quadruple deletion mutant of PpCSP1 and three closely related PpCSP genes exhibits attenuated reprogramming indicating that the PpCSP genes function redundantly in cellular reprogramming. Taken together, these data demonstrate a positive role of PpCSP1 in reprogramming, which is similar to the function of mammalian Lin28.", "classifications": [ { "id": "Sato", "label": "Group Sato", "parent": "Tsuchiya", "type": "group" }, { "id": "Tsuchiya", "label": "Team Tsuchiya", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Chen", "last_name": "Li", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Sako", "name": null }, { "creator_type": "author", "first_name": "Akihiro", "last_name": "Imai", "name": null }, { "creator_type": "author", "first_name": "Tomoaki", "last_name": "Nishiyama", "name": null }, { "creator_type": "author", "first_name": "Kari", "last_name": "Thompson", "name": null }, { "creator_type": "author", "first_name": "Minoru", "last_name": "Kubo", "name": null }, { "creator_type": "author", "first_name": "Yuji", "last_name": "Hiwatashi", "name": null }, { "creator_type": "author", "first_name": "Yukiko", "last_name": "Kabeya", "name": null }, { "creator_type": "author", "first_name": "Dale", "last_name": "Karlson", "name": null }, { "creator_type": "author", "first_name": "Shu-Hsing", "last_name": "Wu", "name": null }, { "creator_type": "author", "first_name": "Masaki", "last_name": "Ishikawa", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Murata", "name": null }, { "creator_type": "author", "first_name": "Philip N.", "last_name": "Benfey", "name": null }, { "creator_type": "author", "first_name": "Yoshikatsu", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Yosuke", "last_name": "Tamada", "name": null }, { "creator_type": "author", "first_name": "Mitsuyasu", "last_name": "Hasebe", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/ncomms14242" }, "pmcid": { "normalized": "PMC5290140" }, "pmid": { "normalized": "28128346" } }, "mesh": [ { "descriptor": "3' Untranslated Regions", "descriptor_ui": "D020413", "major_topic": false }, { "descriptor": "Bryopsida", "descriptor_ui": "D019068", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Cellular Reprogramming", "descriptor_ui": "D065150", "major_topic": false }, { "descriptor": "Cold Shock Proteins and Peptides", "descriptor_ui": "D057773", "major_topic": false }, { "descriptor": "Gene Expression Regulation, Plant", "descriptor_ui": "D018506", "major_topic": false }, { "descriptor": "Plant Leaves", "descriptor_ui": "D018515", "major_topic": false }, { "descriptor": "Plant Proteins", "descriptor_ui": "D010940", "major_topic": false }, { "descriptor": "Plants, Genetically Modified", "descriptor_ui": "D030821", "major_topic": false }, { "descriptor": "Protein Domains", "descriptor_ui": "D000072417", "major_topic": false }, { "descriptor": "Stem Cells", "descriptor_ui": "D013234", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Jan 27", "date_precision": "day", "issue": "", "normalized_date": "2017-01-27", "pages": "14242", "proceedings_title": null, "publisher": "", "title": "Nature communications", "volume": "8", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "A Lin28 homologue reprograms differentiated cells to stem cells in the moss Physcomitrella patens.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Two recent studies in Cell and Science demonstrate the reconstruction of global mechanistic networks and identification of regulatory principles from multi-omics data.", "classifications": [ { "id": "Kuroda", "label": "Group Kuroda", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Katsuyuki", "last_name": "Yugi", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Kuroda", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.cels.2017.01.007" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "28125790" } }, "mesh": [ { "descriptor": "Arginine", "descriptor_ui": "D001120", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Neoplasms", "descriptor_ui": "D009369", "major_topic": true }, { "descriptor": "T-Lymphocytes", "descriptor_ui": "D013601", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Jan 25", "date_precision": "day", "issue": "1", "normalized_date": "2017-01-25", "pages": "19-20", "proceedings_title": null, "publisher": "", "title": "Cell systems", "volume": "4", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Metabolism-Centric Trans-Omics.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The spectrum of genetic mutations differs among cancers in different organs, implying a cellular context-dependent effect for genetic aberrations. However, the extent to which the cellular context affects the consequences of oncogenic mutations remains to be fully elucidated. We reprogrammed colon tumor cells in an Apc(Min/+) (adenomatous polyposis coli) mouse model, in which the loss of the Apc gene plays a critical role in tumor development and subsequently, established reprogrammed tumor cells (RTCs) that exhibit pluripotent stem cell (PSC)-like signatures of gene expression. We show that the majority of the genes in RTCs that were affected by Apc mutations did not overlap with the genes affected in the intestine. RTCs lacked pluripotency but exhibited an increased expression of Cdx2 and a differentiation propensity that was biased toward the trophectoderm cell lineage. Genetic rescue of the mutated Apc allele conferred pluripotency on RTCs and enabled their differentiation into various cell types in vivo. The redisruption of Apc in RTC-derived differentiated cells resulted in neoplastic growth that was exclusive to the intestine, but the majority of the intestinal lesions remained as pretumoral microadenomas. These results highlight the significant influence of cellular context on gene regulation, cellular plasticity, and cellular behavior in response to the loss of the Apc function. Our results also imply that the transition from microadenomas to macroscopic tumors is reprogrammable, which underscores the importance of epigenetic regulation on tumor promotion.", "classifications": [ { "id": "Yamamoto", "label": "Group Yamamoto", "parent": "Toyoshima", "type": "group" }, { "id": "Toyoshima", "label": "Team Toyoshima", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Kyoichi", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Yosuke", "last_name": "Yamada", "name": null }, { "creator_type": "author", "first_name": "Katsunori", "last_name": "Semi", "name": null }, { "creator_type": "author", "first_name": "Masaki", "last_name": "Yagi", "name": null }, { "creator_type": "author", "first_name": "Akito", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Fumiaki", "last_name": "Itakura", "name": null }, { "creator_type": "author", "first_name": "Hitomi", "last_name": "Aoki", "name": null }, { "creator_type": "author", "first_name": "Takahiro", "last_name": "Kunisada", "name": null }, { "creator_type": "author", "first_name": "Knut", "last_name": "Woltjen", "name": null }, { "creator_type": "author", "first_name": "Hironori", "last_name": "Haga", "name": null }, { "creator_type": "author", "first_name": "Yoshiharu", "last_name": "Sakai", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Yasuhiro", "last_name": "Yamada", "name": null } ], "identifiers": { "doi": { "normalized": "10.1073/pnas.1614197114" }, "pmcid": { "normalized": "PMC5278462" }, "pmid": { "normalized": "28057861" } }, "mesh": [ { "descriptor": "Adenomatous Polyposis Coli", "descriptor_ui": "D011125", "major_topic": false }, { "descriptor": "Alleles", "descriptor_ui": "D000483", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Lineage", "descriptor_ui": "D019070", "major_topic": false }, { "descriptor": "Cell Plasticity", "descriptor_ui": "D000066670", "major_topic": false }, { "descriptor": "Colonic Neoplasms", "descriptor_ui": "D003110", "major_topic": false }, { "descriptor": "Epigenesis, Genetic", "descriptor_ui": "D044127", "major_topic": false }, { "descriptor": "Gene Expression", "descriptor_ui": "D015870", "major_topic": false }, { "descriptor": "Gene Expression Regulation", "descriptor_ui": "D005786", "major_topic": false }, { "descriptor": "Gene Expression Regulation, Neoplastic", "descriptor_ui": "D015972", "major_topic": false }, { "descriptor": "Genes, APC", "descriptor_ui": "D017491", "major_topic": false }, { "descriptor": "Intestinal Mucosa", "descriptor_ui": "D007413", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": false }, { "descriptor": "Pluripotent Stem Cells", "descriptor_ui": "D039904", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Jan 24", "date_precision": "day", "issue": "4", "normalized_date": "2017-01-24", "pages": "758-763", "proceedings_title": null, "publisher": "", "title": "Proceedings of the National Academy of Sciences of the United States of America", "volume": "114", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Cellular context-dependent consequences of Apc mutations on gene regulation and cellular behavior.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Dry-cured hams are popular among consumers. To increase the attractiveness of the product, objective analytical methods and algorithms to evaluate the relationship between observable properties and consumer acceptability are required. In this study, metabolomics, which is used for quantitative profiling of hundreds of small molecules, was applied to 12 kinds of dry-cured hams from Japan and Europe. In total, 203 charged metabolites, including amino acids, organic acids, nucleotides, and peptides, were successfully identified and quantified. Metabolite profiles were compared for the samples with different countries of origin and processing methods (e.g., smoking or use of a starter culture). Principal component analysis of the metabolite profiles with sensory properties revealed significant correlations for redness, homogeneity, and fat whiteness. This approach could be used to design new ham products by objective evaluation of various features.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Masahiro", "last_name": "Sugimoto", "name": null }, { "creator_type": "author", "first_name": "Shinichi", "last_name": "Obiya", "name": null }, { "creator_type": "author", "first_name": "Miku", "last_name": "Kaneko", "name": null }, { "creator_type": "author", "first_name": "Ayame", "last_name": "Enomoto", "name": null }, { "creator_type": "author", "first_name": "Mayu", "last_name": "Honma", "name": null }, { "creator_type": "author", "first_name": "Masataka", "last_name": "Wakayama", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Masaru", "last_name": "Tomita", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/acs.jafc.6b03844" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "27951640" } }, "mesh": [ { "descriptor": "Amino Acids", "descriptor_ui": "D000596", "major_topic": false }, { "descriptor": "Europe", "descriptor_ui": "D005060", "major_topic": false }, { "descriptor": "Food Analysis", "descriptor_ui": "D005504", "major_topic": false }, { "descriptor": "Food Handling", "descriptor_ui": "D005511", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Japan", "descriptor_ui": "D007564", "major_topic": false }, { "descriptor": "Metabolome", "descriptor_ui": "D055442", "major_topic": true }, { "descriptor": "Metabolomics", "descriptor_ui": "D055432", "major_topic": false }, { "descriptor": "Peptides", "descriptor_ui": "D010455", "major_topic": false }, { "descriptor": "Principal Component Analysis", "descriptor_ui": "D025341", "major_topic": false }, { "descriptor": "Red Meat", "descriptor_ui": "D000069466", "major_topic": false }, { "descriptor": "Taste", "descriptor_ui": "D013649", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Jan 18", "date_precision": "day", "issue": "2", "normalized_date": "2017-01-18", "pages": "402-410", "proceedings_title": null, "publisher": "", "title": "Journal of agricultural and food chemistry", "volume": "65", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Metabolomic Profiling as a Possible Reverse Engineering Tool for Estimating Processing Conditions of Dry-Cured Hams.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Unsymmetrical cyanine dyes, such as thiazole orange, are useful for the detection of nucleic acids with fluorescence because they dramatically enhance the fluorescence upon binding to nucleic acids. Herein, we synthesized a series of unsymmetrical cyanine dyes and evaluated their fluorescence properties. A systematic structure-property relationship study has revealed that the dialkylamino group at the 2-position of quinoline in a series of unsymmetrical cyanine dyes plays a critical role in the fluorescence enhancement. Four newly designed unsymmetrical cyanine dyes showed negligible intrinsic fluorescence in the free state and strong fluorescence upon binding to double-stranded DNA (dsDNA) with a quantum yield of 0.53 to 0.90, which is 2 to 3 times higher than previous unsymmetrical cyanine dyes. A detailed analysis of the fluorescence lifetime revealed that the dialkylamino group at the 2-position of quinoline suppressed nonradiative decay in favor of increased fluorescence quantum yield. Moreover, these newly developed dyes were able to stain the nucleus specifically in fixed HeLa cells examined by using a confocal laser-scanning microscope.", "classifications": [ { "id": "Sato", "label": "Group Sato", "parent": "Tsuchiya", "type": "group" }, { "id": "Tsuchiya", "label": "Team Tsuchiya", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Kakishi", "last_name": "Uno", "name": null }, { "creator_type": "author", "first_name": "Taeko", "last_name": "Sasaki", "name": null }, { "creator_type": "author", "first_name": "Nagisa", "last_name": "Sugimoto", "name": null }, { "creator_type": "author", "first_name": "Hideto", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Taishi", "last_name": "Nishihara", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Hagihara", "name": null }, { "creator_type": "author", "first_name": "Tetsuya", "last_name": "Higashiyama", "name": null }, { "creator_type": "author", "first_name": "Narie", "last_name": "Sasaki", "name": null }, { "creator_type": "author", "first_name": "Yoshikatsu", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Kenichiro", "last_name": "Itami", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/asia.201601430" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "27860278" } }, "mesh": [ { "descriptor": "Carbocyanines", "descriptor_ui": "D002232", "major_topic": false }, { "descriptor": "DNA Probes", "descriptor_ui": "D015342", "major_topic": false }, { "descriptor": "Fluorescent Dyes", "descriptor_ui": "D005456", "major_topic": false }, { "descriptor": "HeLa Cells", "descriptor_ui": "D006367", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Limit of Detection", "descriptor_ui": "D057230", "major_topic": false }, { "descriptor": "Microscopy, Confocal", "descriptor_ui": "D018613", "major_topic": false }, { "descriptor": "Molecular Structure", "descriptor_ui": "D015394", "major_topic": false }, { "descriptor": "Phantoms, Imaging", "descriptor_ui": "D019047", "major_topic": false }, { "descriptor": "Quinolines", "descriptor_ui": "D011804", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Jan 17", "date_precision": "day", "issue": "2", "normalized_date": "2017-01-17", "pages": "233-238", "proceedings_title": null, "publisher": "", "title": "Chemistry, an Asian journal", "volume": "12", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Key Structural Elements of Unsymmetrical Cyanine Dyes for Highly Sensitive Fluorescence Turn-On DNA Probes.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "To evaluate associations by EGFR mutation status for lung adenocarcinoma risk among never-smoking Asian women, we conducted a meta-analysis of 11 loci previously identified in genome-wide association studies (GWAS). Genotyping in an additional 10,780 never-smoking cases and 10,938 never-smoking controls from Asia confirmed associations with eight known single nucleotide polymorphisms (SNPs). Two new signals were observed at genome-wide significance (P < 5 x 10-8), namely, rs7216064 (17q24.3, BPTF), for overall lung adenocarcinoma risk, and rs3817963 (6p21.3, BTNL2) which is specific to cases with EGFR mutations. In further sub-analyses by EGFR status, rs9387478 (ROS1/DCBLD1) and rs2179920 (HLA-DPB1) showed stronger estimated associations in EGFR-positive compared to EGFR-negative cases. Comparison of the overall associations with published results in Western populations revealed that the majority of these findings were distinct, underscoring the importance of distinct contributing factors for smoking and non-smoking lung cancer. Our results extend the catalogue of regions associated with lung adenocarcinoma in non-smoking Asian women and highlight the importance of how the germline could inform risk for specific tumour mutation patterns, which could have important translational implications.", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Wei Jie", "last_name": "Seow", "name": null }, { "creator_type": "author", "first_name": "Keitaro", "last_name": "Matsuo", "name": null }, { "creator_type": "author", "first_name": "Chao Agnes", "last_name": "Hsiung", "name": null }, { "creator_type": "author", "first_name": "Kouya", "last_name": "Shiraishi", "name": null }, { "creator_type": "author", "first_name": "Minsun", "last_name": "Song", "name": null }, { "creator_type": "author", "first_name": "Hee Nam", "last_name": "Kim", "name": null }, { "creator_type": "author", "first_name": "Maria Pik", "last_name": "Wong", "name": null }, { "creator_type": "author", "first_name": "Yun-Chul", "last_name": "Hong", "name": null }, { "creator_type": "author", "first_name": "H. 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"last_name": "Chen", "name": null }, { "creator_type": "author", "first_name": "Yi-Long", "last_name": "Wu", "name": null }, { "creator_type": "author", "first_name": "Maria Teresa", "last_name": "Landi", "name": null }, { "creator_type": "author", "first_name": "Hongbing", "last_name": "Shen", "name": null }, { "creator_type": "author", "first_name": "Nathaniel", "last_name": "Rothman", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Kohno", "name": null }, { "creator_type": "author", "first_name": "Stephen J.", "last_name": "Chanock", "name": null }, { "creator_type": "author", "first_name": "Qing", "last_name": "Lan", "name": null } ], "identifiers": { "doi": { "normalized": "10.1093/hmg/ddw414" }, "pmcid": { "normalized": "PMC5856088" }, "pmid": { "normalized": "28025329" } }, "mesh": [ { "descriptor": "Adenocarcinoma", "descriptor_ui": "D000230", "major_topic": false }, { "descriptor": "Adenocarcinoma of Lung", "descriptor_ui": "D000077192", "major_topic": false }, { "descriptor": "Antigens, Nuclear", "descriptor_ui": "D034961", "major_topic": false }, { "descriptor": "Asian People", "descriptor_ui": "D044466", "major_topic": false }, { "descriptor": "Bromodomain Containing Proteins", "descriptor_ui": "D000092468", "major_topic": false }, { "descriptor": "Butyrophilins", "descriptor_ui": "D000071797", "major_topic": false }, { "descriptor": "Case-Control Studies", "descriptor_ui": "D016022", "major_topic": false }, { "descriptor": "ErbB Receptors", "descriptor_ui": "D066246", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Genetic Predisposition to Disease", "descriptor_ui": "D020022", "major_topic": false }, { "descriptor": "Genome-Wide Association Study", "descriptor_ui": "D055106", "major_topic": false }, { "descriptor": "Genotype", "descriptor_ui": "D005838", "major_topic": false }, { "descriptor": "Germ-Line Mutation", "descriptor_ui": "D018095", "major_topic": false }, { "descriptor": "HLA-DP beta-Chains", "descriptor_ui": "D059868", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Lung Neoplasms", "descriptor_ui": "D008175", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Membrane Proteins", "descriptor_ui": "D008565", "major_topic": false }, { "descriptor": "Nerve Tissue Proteins", "descriptor_ui": "D009419", "major_topic": false }, { "descriptor": "Polymorphism, Single Nucleotide", "descriptor_ui": "D020641", "major_topic": false }, { "descriptor": "Sex Characteristics", "descriptor_ui": "D012727", "major_topic": false }, { "descriptor": "Smoking", "descriptor_ui": "D012907", "major_topic": false }, { "descriptor": "Transcription Factors", "descriptor_ui": "D014157", "major_topic": false }, { "descriptor": "White People", "descriptor_ui": "D044465", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Jan 15", "date_precision": "day", "issue": "2", "normalized_date": "2017-01-15", "pages": "454-465", "proceedings_title": null, "publisher": "", "title": "Human molecular genetics", "volume": "26", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Association between GWAS-identified lung adenocarcinoma susceptibility loci and EGFR mutations in never-smoking Asian women, and comparison with findings from Western populations.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Novel APOBEC1 target 1 (Nat1) (also known as \"p97,\" \"Dap5,\" and \"Eif4g2\") is a ubiquitously expressed cytoplasmic protein that is homologous to the C-terminal two thirds of eukaryotic translation initiation factor 4G (Eif4g1). We previously showed that Nat1-null mouse embryonic stem cells (mES cells) are resistant to differentiation. In the current study, we found that NAT1 and eIF4G1 share many binding proteins, such as the eukaryotic translation initiation factors eIF3 and eIF4A and ribosomal proteins. However, NAT1 did not bind to eIF4E or poly(A)-binding proteins, which are critical for cap-dependent translation initiation. In contrast, compared with eIF4G1, NAT1 preferentially interacted with eIF2, fragile X mental retardation proteins (FMR), and related proteins and especially with members of the proline-rich and coiled-coil-containing protein 2 (PRRC2) family. We also found that Nat1-null mES cells possess a transcriptional profile similar, although not identical, to the ground state, which is established in wild-type mES cells when treated with inhibitors of the ERK and glycogen synthase kinase 3 (GSK3) signaling pathways. In Nat1-null mES cells, the ERK pathway is suppressed even without inhibitors. Ribosome profiling revealed that translation of mitogen-activated protein kinase kinase kinase 3 (Map3k3) and son of sevenless homolog 1 (Sos1) is suppressed in the absence of Nat1 Forced expression of Map3k3 induced differentiation of Nat1-null mES cells. These data collectively show that Nat1 is involved in the translation of proteins that are required for cell differentiation.", "classifications": [ { "id": "Yamamoto", "label": "Group Yamamoto", "parent": "Toyoshima", "type": "group" }, { "id": "Toyoshima", "label": "Team Toyoshima", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Hayami", "last_name": "Sugiyama", "name": null }, { "creator_type": "author", "first_name": "Kazutoshi", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Mio", "last_name": "Iwasaki", "name": null }, { "creator_type": "author", "first_name": "Megumi", "last_name": "Narita", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Tim A.", "last_name": "Rand", "name": null }, { "creator_type": "author", "first_name": "Masato", "last_name": "Nakagawa", "name": null }, { "creator_type": "author", "first_name": "Akira", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Yamanaka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1073/pnas.1617234114" }, "pmcid": { "normalized": "PMC5240712" }, "pmid": { "normalized": "28003464" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Arylamine N-Acetyltransferase", "descriptor_ui": "D001191", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Eukaryotic Initiation Factor-4G", "descriptor_ui": "D039603", "major_topic": false }, { "descriptor": "Glycogen Synthase Kinase 3", "descriptor_ui": "D038362", "major_topic": false }, { "descriptor": "Isoenzymes", "descriptor_ui": "D007527", "major_topic": false }, { "descriptor": "MAP Kinase Kinase Kinase 3", "descriptor_ui": "D048748", "major_topic": false }, { "descriptor": "MAP Kinase Signaling System", "descriptor_ui": "D020935", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mouse Embryonic Stem Cells", "descriptor_ui": "D000066450", "major_topic": false }, { "descriptor": "Protein Binding", "descriptor_ui": "D011485", "major_topic": false }, { "descriptor": "Protein Biosynthesis", "descriptor_ui": "D014176", "major_topic": false }, { "descriptor": "Ribosomes", "descriptor_ui": "D012270", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "SOS1 Protein", "descriptor_ui": "D020837", "major_topic": false }, { "descriptor": "Transcription, Genetic", "descriptor_ui": "D014158", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Jan 10", "date_precision": "day", "issue": "2", "normalized_date": "2017-01-10", "pages": "340-345", "proceedings_title": null, "publisher": "", "title": "Proceedings of the National Academy of Sciences of the United States of America", "volume": "114", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Nat1 promotes translation of specific proteins that induce differentiation of mouse embryonic stem cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The 2-methylthio (ms(2)) modification at A37 of tRNAs is critical for accurate decoding, and contributes to metabolic homeostasis in mammals. However, the regulatory mechanism of ms(2) modification remains largely unknown. Here, we report that cysteine hydropersulfide (CysSSH), a newly identified reactive sulfur species, is involved in ms(2) modification in cells. The suppression of intracellular CysSSH production rapidly reduced ms(2) modification, which was rescued by the application of an exogenous CysSSH donor. Using a unique and stable isotope-labeled CysSSH donor, we show that CysSSH was capable of specifically transferring its reactive sulfur atom to the cysteine residues of ms(2)-modifying enzymes as well as ms(2) modification. Furthermore, the suppression of CysSSH production impaired insulin secretion and caused glucose intolerance in both a pancreatic beta-cell line and mouse model. These results demonstrate that intracellular CysSSH is a novel sulfur source for ms(2) modification, and that it contributes to insulin secretion.", "classifications": [ { "id": "Akaike", "label": "Group Akaike", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Nozomu", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Fan-Yan", "last_name": "Wei", "name": null }, { "creator_type": "author", "first_name": "Sayaka", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Mayumi", "last_name": "Hirayama", "name": null }, { "creator_type": "author", "first_name": "Yuya", "last_name": "Ohuchi", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Fujimura", "name": null }, { "creator_type": "author", "first_name": "Taku", "last_name": "Kaitsuka", "name": null }, { "creator_type": "author", "first_name": "Isao", "last_name": "Ishii", "name": null }, { "creator_type": "author", "first_name": "Tomohiro", "last_name": "Sawa", "name": null }, { "creator_type": "author", "first_name": "Hideki", "last_name": "Nakayama", "name": null }, { "creator_type": "author", "first_name": "Takaaki", "last_name": "Akaike", "name": null }, { "creator_type": "author", "first_name": "Kazuhito", "last_name": "Tomizawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1093/nar/gkw745" }, "pmcid": { "normalized": "PMC5224495" }, "pmid": { "normalized": "27568003" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "Cysteine", "descriptor_ui": "D003545", "major_topic": false }, { "descriptor": "Disulfides", "descriptor_ui": "D004220", "major_topic": false }, { "descriptor": "Free Radicals", "descriptor_ui": "D005609", "major_topic": false }, { "descriptor": "Gene Expression Regulation", "descriptor_ui": "D005786", "major_topic": false }, { "descriptor": "HeLa Cells", "descriptor_ui": "D006367", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Insulin", "descriptor_ui": "D007328", "major_topic": false }, { "descriptor": "Insulin Secretion", "descriptor_ui": "D000078790", "major_topic": false }, { "descriptor": "Insulin-Secreting Cells", "descriptor_ui": "D050417", "major_topic": false }, { "descriptor": "Isotope Labeling", "descriptor_ui": "D007553", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Nerve Tissue Proteins", "descriptor_ui": "D009419", "major_topic": false }, { "descriptor": "Nucleic Acid Conformation", "descriptor_ui": "D009690", "major_topic": false }, { "descriptor": "RNA, Transfer", "descriptor_ui": "D012343", "major_topic": false }, { "descriptor": "Sulfhydryl Compounds", "descriptor_ui": "D013438", "major_topic": false }, { "descriptor": "Sulfur", "descriptor_ui": "D013455", "major_topic": false }, { "descriptor": "tRNA Methyltransferases", "descriptor_ui": "D012359", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Jan 9", "date_precision": "day", "issue": "1", "normalized_date": "2017-01-09", "pages": "435-445", "proceedings_title": null, "publisher": "", "title": "Nucleic acids research", "volume": "45", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Reactive sulfur species regulate tRNA methylthiolation and contribute to insulin secretion.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Dipeptidyl peptidase 4 inhibitors are used worldwide in the management of diabetes, but their role in the prevention or treatment of cardiovascular disorders has yet to be defined. We found that linagliptin, a DPP-4 inhibitor, suppressed capillary rarefaction in the hearts of mice with dietary obesity. Metabolomic analysis performed with capillary electrophoresis/mass spectrometry (LC-MS/MS) showed that linagliptin promoted favorable metabolic remodeling in cardiac tissue, which was characterized by high levels of citrulline and creatine. DNA microarray analysis revealed that the cardiac tissue level of early growth response protein 1 (EGR-1), which activates angiogenesis, was significantly reduced in untreated mice with dietary obesity, while this decrease was inhibited by administration of linagliptin. Mature fibroblast growth factor 2 (FGF-2) has a putative truncation site for DPP-4 at the NH2-terminal, and LC-MS/MS showed that recombinant DPP-4 protein cleaved the NH2-terminal dipeptides of mature FGF-2. Incubation of cultured neonatal rat cardiomyocytes with FGF-2 increased Egr1 expression, while it was suppressed by recombinant DPP-4 protein. Furthermore, vascular endothelial growth factor-A had a critical role in mediating FGF-2/EGR-1 signaling. In conclusion, pharmacological inhibition of DPP-4 suppressed capillary rarefaction and contributed to favorable remodeling of cardiac metabolism in mice with dietary obesity.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Masayoshi", "last_name": "Suda", "name": null }, { "creator_type": "author", "first_name": "Ippei", "last_name": "Shimizu", "name": null }, { "creator_type": "author", "first_name": "Yohko", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Yuka", "last_name": "Hayashi", "name": null }, { "creator_type": "author", "first_name": "Ryutaro", "last_name": "Ikegami", "name": null }, { "creator_type": "author", "first_name": "Goro", "last_name": "Katsuumi", "name": null }, { "creator_type": "author", "first_name": "Takayuki", "last_name": "Wakasugi", "name": null }, { "creator_type": "author", "first_name": "Yutaka", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Shujiro", "last_name": "Okuda", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Tohru", "last_name": "Minamino", "name": null } ], "identifiers": { "doi": { "normalized": "10.1371/journal.pone.0182422" }, "pmcid": { "normalized": "PMC5542565" }, "pmid": { "normalized": "28771625" } }, "mesh": [ { "descriptor": "Amino Acid Sequence", "descriptor_ui": "D000595", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Dipeptidyl Peptidase 4", "descriptor_ui": "D018819", "major_topic": false }, { "descriptor": "Dipeptidyl-Peptidase IV Inhibitors", "descriptor_ui": "D054873", "major_topic": false }, { "descriptor": "Early Growth Response Protein 1", "descriptor_ui": "D051766", "major_topic": false }, { "descriptor": "Fibroblast Growth Factor 2", "descriptor_ui": "D016222", "major_topic": false }, { "descriptor": "Gene Expression Regulation", "descriptor_ui": "D005786", "major_topic": false }, { "descriptor": "Heart Diseases", "descriptor_ui": "D006331", "major_topic": false }, { "descriptor": "Linagliptin", "descriptor_ui": "D000069476", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Myocardial Ischemia", "descriptor_ui": "D017202", "major_topic": false }, { "descriptor": "Obesity", "descriptor_ui": "D009765", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Rats, Wistar", "descriptor_ui": "D017208", "major_topic": false }, { "descriptor": "Sequence Homology", "descriptor_ui": "D017385", "major_topic": false }, { "descriptor": "Systole", "descriptor_ui": "D013599", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017", "date_precision": "year", "issue": "8", "normalized_date": "2017", "pages": "e0182422", "proceedings_title": null, "publisher": "", "title": "PloS one", "volume": "12", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Inhibition of dipeptidyl peptidase-4 ameliorates cardiac ischemia and systolic dysfunction by up-regulating the FGF-2/EGR-1 pathway.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Raman spectroscopy allows label-free, minimally invasive, and accurate detection of peripheral nerves. However, the conventional Raman imaging technique is time-consuming when measuring a large area of a sample. Establishing a method for rapidly acquiring spatial distribution of a bundle of peripheral nerve fibers is an essential step for Raman spectroscopy towards application in clinical surgery. Here we present a multipoint Raman spectroscopic technique for rapid peripheral nerve imaging. In only 5 seconds, spectra at 32 points situated on ex vivo rat peripheral nerve bundles and adjoining connective tissues were acquired. Principal component regression and discriminant analysis of spectra revealed that the sensitivity, specificity and accuracy for nerve detection were 85.8%, 96.0%, and 90.8%, respectively. Of 158 peripheral nerves, 152 (96.2%) showed ratio of the number of nerve-positive prediction points to the total measurement points being 0.4 or larger, whereas 119 (99.2%) connective tissues among 120 showed ratio smaller than 0.4. Based on the ratio and a bright-field image of the sample, accurate visualization of peripheral nerves was implemented. The results indicated that the multipoint Raman spectroscopic technique is capable of rapid and accurate peripheral nerve imaging.", "classifications": [ { "id": "Tanaka", "label": "Group Tanaka", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yasuaki", "last_name": "Kumamoto", "name": null }, { "creator_type": "author", "first_name": "Yoshinori", "last_name": "Harada", "name": null }, { "creator_type": "author", "first_name": "Hideo", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Tetsuro", "last_name": "Takamatsu", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41598-017-00995-y" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "28405007" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Connective Tissue", "descriptor_ui": "D003238", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Optical Imaging", "descriptor_ui": "D061848", "major_topic": false }, { "descriptor": "Peripheral Nerves", "descriptor_ui": "D010525", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Rats, Wistar", "descriptor_ui": "D017208", "major_topic": false }, { "descriptor": "Sensitivity and Specificity", "descriptor_ui": "D012680", "major_topic": false }, { "descriptor": "Spectrum Analysis, Raman", "descriptor_ui": "D013059", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017", "date_precision": "year", "issue": "", "normalized_date": "2017", "pages": "", "proceedings_title": null, "publisher": "", "title": "Scientific Reports", "volume": "7", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Rapid and accurate peripheral nerve imaging by multipoint Raman spectroscopy.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "We consider ordinary differential equation (ODE) model for a pathway network that arises in extracellular matrix (ECM) degradation. For solving the ODEs, we propose applying the mass conservation law (MCL), together with a stoichiometry called doubling rule, to them. Then it leads to extracting new units of variables in the ODEs that can be solved explicitly, at least in principle. The simulation results for the ODE solutions show that the numerical solutions are indeed in good accord with theoretical solutions and satisfy the MALs.", "classifications": [ { "id": "Suzuki", "label": "Group Suzuki", "parent": "Takekawa", "type": "group" }, { "id": "Takekawa", "label": "Team Takekawa", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Shuji", "last_name": "Kawasaki", "name": null }, { "creator_type": "author", "first_name": "Dhisa", "last_name": "Minerva", "name": null }, { "creator_type": "author", "first_name": "Keiko", "last_name": "Itano", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Suzuki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1155/2017/5924270" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "28638440" } }, "mesh": [ { "descriptor": "Computer Simulation", "descriptor_ui": "D003198", "major_topic": false }, { "descriptor": "Extracellular Matrix", "descriptor_ui": "D005109", "major_topic": false }, { "descriptor": "Models, Theoretical", "descriptor_ui": "D008962", "major_topic": true }, { "descriptor": "Nonlinear Dynamics", "descriptor_ui": "D017711", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017", "date_precision": "year", "issue": "", "normalized_date": "2017", "pages": "", "proceedings_title": null, "publisher": "", "title": "Computational and Mathematical Methods in Medicine", "volume": "2017", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Finding Solvable Units of Variables in Nonlinear ODEs of ECM Degradation Pathway Network.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Cell populations in multicellular organisms show genetic and non-genetic heterogeneity, even in undifferentiated tissues of multipotent cells during development and tumorigenesis. The heterogeneity causes difference of mechanical properties, such as, cell bond tension or adhesion, at the cell–cell interface, which determine the shape of clonal population boundaries via cell sorting or mixing. The boundary shape could alter the degree of cell–cell contacts and thus influence the physiological consequences of sorting or mixing at the boundary (e.g., tumor suppression or progression), suggesting that the cell mechanics could help clarify the physiology of heterogeneous tissues. While precise inference of mechanical tension loaded at each cell–cell contacts has been extensively developed, there has been little progress on how to distinguish the population-boundary geometry and identify the cause of geometry in heterogeneous tissues. We developed a pipeline by combining multivariate analysis of clone shape with tissue mechanical simulations. We examined clones with four different genotypes within Drosophila wing imaginal discs: wild-type, tartan (trn) overexpression, hibris (hbs) overexpression, and Eph RNAi. Although the clones were previously known to exhibit smoothed or convoluted morphologies, their mechanical properties were unknown. By applying a multivariate analysis to multiple criteria used to quantify the clone shapes based on individual cell shapes, we found the optimal criteria to distinguish not only among the four genotypes, but also non-genetic heterogeneity from genetic one. The efficient segregation of clone shape enabled us to quantitatively compare experimental data with tissue mechanical simulations. As a result, we identified the mechanical basis contributed to clone shape of distinct genotypes. The present pipeline will promote the understanding of the functions of mechanical interactions in heterogeneous tissue in a non-invasive manner.", "classifications": [ { "id": "Fujimoto", "label": "Group Fujimoto", "parent": "Ueda", "type": "group" }, { "id": "Ueda", "label": "Team Ueda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Alice", "last_name": "Tsuboi", "name": null }, { "creator_type": "author", "first_name": "Daiki", "last_name": "Umetsu", "name": null }, { "creator_type": "author", "first_name": "Erina", "last_name": "Kuranaga", "name": null }, { "creator_type": "author", "first_name": "Koichi", "last_name": "Fujimoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.3389/fcell.2017.00068" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "28824908" } }, "mesh": [], "publication": { "conference_name": null, "date": "2017", "date_precision": "year", "issue": "", "normalized_date": "2017", "pages": "", "proceedings_title": null, "publisher": "", "title": "Frontiers in Cell and Developmental Biology", "volume": "5", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Inference of Cell Mechanics in Heterogeneous Epithelial Tissue Based on Multivariate Clone Shape Quantification.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Fluorescence lifetime imaging (FLIM) has now been used in many bioscience fields, which comes from the quantification of fluorescence lifetime. The procedure for obtaining lifetime images is very similar to that used in fluorescence microscopy. However, obtaining reliable lifetime images requires an understanding of the theory of fluorescence lifetime, principle of FLIM systems, and evaluation procedure of intracellular environments. In this chapter, the materials, methods, and notes on FLIM measurements have been described, in conjunction with a brief explanation of the background of FLIM.", "classifications": [ { "id": "Nakabayashi", "label": "Group Nakabayashi", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Takakazu", "last_name": "Nakabayashi", "name": null }, { "creator_type": "author", "first_name": "Kamlesh", "last_name": "Awasthi", "name": null }, { "creator_type": "author", "first_name": "Nobuhiro", "last_name": "Ohta", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/978-3-319-67358-5_8" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "29080134" } }, "mesh": [ { "descriptor": "Cell Nucleus", "descriptor_ui": "D002467", "major_topic": false }, { "descriptor": "Fluorescence Resonance Energy Transfer", "descriptor_ui": "D031541", "major_topic": false }, { "descriptor": "Fluorescent Dyes", "descriptor_ui": "D005456", "major_topic": false }, { "descriptor": "HeLa Cells", "descriptor_ui": "D006367", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Hydrogen-Ion Concentration", "descriptor_ui": "D006863", "major_topic": false }, { "descriptor": "Lasers", "descriptor_ui": "D007834", "major_topic": false }, { "descriptor": "Mitochondria", "descriptor_ui": "D008928", "major_topic": false }, { "descriptor": "NAD", "descriptor_ui": "D009243", "major_topic": false }, { "descriptor": "Optical Imaging", "descriptor_ui": "D061848", "major_topic": false }, { "descriptor": "Porphyrins", "descriptor_ui": "D011166", "major_topic": false }, { "descriptor": "Single-Cell Analysis", "descriptor_ui": "D059010", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017", "date_precision": "year", "issue": "", "normalized_date": "2017", "pages": "121-133", "proceedings_title": null, "publisher": "", "title": "Advances in experimental medicine and biology", "volume": "1035", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Application of Fluorescence Lifetime Imaging (FLIM) to Measure Intracellular Environments in a Single Cell.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "", "classifications": [ { "id": "Nikaido", "label": "Group Nikaido", "parent": "Fujiwara", "type": "group" }, { "id": "Fujiwara", "label": "Team Fujiwara", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yohei", "last_name": "Sasagawa", "name": null }, { "creator_type": "author", "first_name": "Itoshi", "last_name": "Nikaido", "name": null }, { "creator_type": "author", "first_name": "Tetsutaro", "last_name": "Hayashi", "name": null }, { "creator_type": "author", "first_name": "Hiroki", "last_name": "Danno", "name": null }, { "creator_type": "author", "first_name": "Kenichiro D.", "last_name": "Uno", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Imai", "name": null }, { "creator_type": "author", "first_name": "Hiroki R.", "last_name": "Ueda", "name": null } ], "identifiers": { "doi": { "normalized": "10.1186/s13059-017-1154-x" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "28100273" } }, "mesh": [], "publication": { "conference_name": null, "date": "2017", "date_precision": "year", "issue": "", "normalized_date": "2017", "pages": "", "proceedings_title": null, "publisher": "", "title": "Genome Biology", "volume": "18", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Erratum to: Quartz-Seq: a highly reproducible and sensitive single-cell RNA sequencing method, reveals non-genetic gene-expression heterogeneity.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The Barnes maze is one of the main behavioral tasks used to study spatial learning and memory. The Barnes maze is a task conducted on \"dry land\" in which animals try to escape from a brightly lit exposed circular open arena to a small dark escape box located under one of several holes at the periphery of the arena. In comparison with another classical spatial learning and memory task, the Morris water maze, the negative reinforcements that motivate animals in the Barnes maze are less severe and less stressful. Furthermore, the Barnes maze is more compatible with recently developed cutting-edge techniques in neural circuit research, such as the miniature brain endoscope or optogenetics. For this study, we developed a lift-type task start system and equipped the Barnes maze with it. The subject mouse is raised up by the lift and released into the maze automatically so that it can start navigating the maze smoothly from exactly the same start position across repeated trials. We believe that a Barnes maze test with a lift-type task start system may be useful for behavioral experiments when combined with head-mounted or wire-connected devices for online imaging and intervention in neural circuits. Furthermore, we introduced a network analysis method for the analysis of the Barnes maze data. Each animal's exploratory behavior in the maze was visualized as a network of nodes and their links, and spatial learning in the maze is described by systematic changes in network structures of search behavior. Network analysis was capable of visualizing and quantitatively analyzing subtle but significant differences in an animal's exploratory behavior in the maze.", "classifications": [ { "id": "Imayoshi", "label": "Group Imayoshi", "parent": "Imayoshi", "type": "group" }, { "id": "Imayoshi", "label": "Team Imayoshi", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yusuke", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Itaru", "last_name": "Imayoshi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1371/journal.pone.0180789" }, "pmcid": { "normalized": "PMC5507260" }, "pmid": { "normalized": "28700627" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Exploratory Behavior", "descriptor_ui": "D005106", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Maze Learning", "descriptor_ui": "D018782", "major_topic": false }, { "descriptor": "Memory", "descriptor_ui": "D008568", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Reaction Time", "descriptor_ui": "D011930", "major_topic": false }, { "descriptor": "Space Perception", "descriptor_ui": "D013028", "major_topic": false }, { "descriptor": "Spatial Learning", "descriptor_ui": "D065853", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017", "date_precision": "year", "issue": "7", "normalized_date": "2017", "pages": "e0180789", "proceedings_title": null, "publisher": "", "title": "PloS one", "volume": "12", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Network analysis of exploratory behaviors of mice in a spatial learning and memory task.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "In the developing embryo, telencephalon arises from the rostral portion of the neural tube. The telencephalon further subdivides into distinct brain regions along the dorsal-ventral (DV) axis by exogenous patterning signals. Here, we describe a protocol for in vitro generation of various telencephalic regions from human embryonic stem cells (ESCs). Dissociated human ESCs are reaggregated in a low-cell-adhesion 96-well plate and cultured as floating aggregates. Telencephalic neural progenitors are efficiently generated when ESC aggregates are cultured in serum-free medium containing TGFbeta inhibitor and Wnt inhibitor. In long-term culture, the telencephalic neural progenitors acquire cortical identities and self-organize a stratified cortical structure as seen in human fetal cortex. By treatment with Shh signal, the telencephalic progenitors acquire ventral (subpallial) identities and generate lateral ganglionic eminence (LGE) and medial ganglionic eminence (MGE). In contrast, by treatment with Wnt and BMP signals, their regional identities shift to more dorsal side that generates choroid plexus and medial palllium (hippocampal primordium).", "classifications": [ { "id": "Eiraku", "label": "Group Eiraku", "parent": "Eiraku", "type": "group" }, { "id": "Eiraku", "label": "Team Eiraku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Taisuke", "last_name": "Kadoshima", "name": null }, { "creator_type": "author", "first_name": "Hideya", "last_name": "Sakaguchi", "name": null }, { "creator_type": "author", "first_name": "Mototsugu", "last_name": "Eiraku", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/978-1-4939-6949-4_1" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "28361306" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Culture Techniques", "descriptor_ui": "D018929", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Embryo, Mammalian", "descriptor_ui": "D004622", "major_topic": false }, { "descriptor": "Ganglion Cysts", "descriptor_ui": "D045888", "major_topic": false }, { "descriptor": "Hippocampus", "descriptor_ui": "D006624", "major_topic": false }, { "descriptor": "Human Embryonic Stem Cells", "descriptor_ui": "D000066449", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Telencephalon", "descriptor_ui": "D013687", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017", "date_precision": "year", "issue": "", "normalized_date": "2017", "pages": "1-16", "proceedings_title": null, "publisher": "", "title": "Methods in molecular biology (Clifton, N.J.)", "volume": "1597", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Generation of Various Telencephalic Regions from Human Embryonic Stem Cells in Three-Dimensional Culture.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Cardiac stiffness, caused by interstitial fibrosis due to deposition of extracellular matrix proteins, is thought as a major clinical outcome of heart failure with preserved ejection fraction (HFpEF). Canonical transient receptor potential (TRPC) subfamily proteins are components of Ca2+-permeable non-selective cation channels activated by receptor stimulation and mechanical stress, and have been attracted attention as a key mediator of maladaptive cardiac remodeling. How TRPC-mediated local Ca2+ influx encodes a specific signal to induce maladaptive cardiac remodeling has been long obscure, but our recent studies suggest a pathophysiological significance of channel activity-independent function of TRPC proteins for amplifying redox signaling in heart. This review introduces the current understanding of the physiological and pathophysiological roles of TRPCs, especially focuses on the role of TRPC3 as a positive regulator of reactive oxygen species (PRROS) in heart. We have revealed that TRPC3 stabilizes NADPH oxidase 2 (Nox2), a membrane-bound reactive oxygen species (ROS)-generating enzyme, by forming stable protein complex with Nox2, which leads to amplification of mechanical stress-induced ROS signaling in cardiomyocytes, resulting in induction of fibrotic responses in cardiomyocytes and cardiac fibroblasts. Thus, the TRPC3 function as PRROS will offer a new therapeutic strategy for the prevention or treatment of HFpEF.", "classifications": [ { "id": "Nishida", "label": "Group Nishida", "parent": "Nishida", "type": "group" }, { "id": "Nishimura", "label": "Group Nishimura", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Takuro", "last_name": "Numaga-Tomita", "name": null }, { "creator_type": "author", "first_name": "Sayaka", "last_name": "Oda", "name": null }, { "creator_type": "author", "first_name": "Tsukasa", "last_name": "Shimauchi", "name": null }, { "creator_type": "author", "first_name": "Akiyuki", "last_name": "Nishimura", "name": null }, { "creator_type": "author", "first_name": "Supachoke", "last_name": "Mangmool", "name": null }, { "creator_type": "author", "first_name": "Motohiro", "last_name": "Nishida", "name": null } ], "identifiers": { "doi": { "normalized": "10.3389/fcvm.2017.00056" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "28936433" } }, "mesh": [], "publication": { "conference_name": null, "date": "2017", "date_precision": "year", "issue": "", "normalized_date": "2017", "pages": "", "proceedings_title": null, "publisher": "", "title": "Frontiers in Cardiovascular Medicine", "volume": "4", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "TRPC3 Channels in Cardiac Fibrosis.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Leucine-rich repeat-containing G-protein coupled receptor 5 (Lgr5) is considered a representative marker of intestinal stem cells from both non-tumor and tumor tissues. However, it remains unclear whether all or only a fraction of Lgr5-positive cells behave as stem cells. Recently, we reported that Lgr5-positive cells from non-tumor and tumor tissues can be classified into overlapping yet distinct groups and that the tumor-specific groups are associated with tumorigenic capability, suggesting that these cells could represent targets for therapeutic intervention.", "classifications": [ { "id": "Okamoto", "label": "Group Okamoto", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Daisuke", "last_name": "Shiokawa", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Okamoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1080/23723556.2017.1335271" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "28868346" } }, "mesh": [], "publication": { "conference_name": null, "date": "2017", "date_precision": "year", "issue": "4", "normalized_date": "2017", "pages": "", "proceedings_title": null, "publisher": "", "title": "Molecular & Cellular Oncology", "volume": "4", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Heterogeneity among Lgr5-positive colon stem cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Recently, a novel culture system consisting of primary hepatocytes structured over a network of endothelial cells on the Engelbreth-Holm-Swarm (EHS) gel has been reported. This in vitro liver model on the EHS gel (IVL(EHS)) has been shown to maintain the expression of hepatic genes and their functional activity. Moreover, the IVL(EHS) was more sensitive to xenobiotics than hepatocyte monocultures, suggesting the potential utility of this culture system for compound hepatotoxicity screening. However, the effect of this three-dimensional structure formation on the cellular metabolic profile of hepatocytes in the IVL(EHS) is not well understood. To address this concern, we performed metabolome analysis using capillary electrophoresis-time of flight mass spectrometry. Between the IVL(EHS) and mono-cultured hepatocytes on the EHS gel, there was no significant difference in the levels of metabolites of the urea cycle and the tricarboxylic acid cycle, essential amino acids, and adenylate energy charge (AEC) which is an important indicator of cellular energy status. On the other hand, acetaminophen-dependent decrease of the AEC in the IVL(EHS) was greater than that in the monoculture, suggesting the higher sensitivity of IVL(EHS) to acetaminophen-induced hepatotoxicity which is caused by metabolic activation of this drug. Further analysis showed that the levels of taurocholate, one of the major conjugated bile acids, were higher in the IVL(EHS) than in the monoculture. Considering that the construction of the IVL(EHS) did not seem to disturb the major cellular metabolism, our findings would strengthen the concept that IVL(EHS) would have beneficial effects on the maintenance of hepatic functions.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yu", "last_name": "Toyoda", "name": null }, { "creator_type": "author", "first_name": "Kasumi", "last_name": "Kashikura", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Yoh-Ichi", "last_name": "Tagawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.2131/jts.42.445" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "28717103" } }, "mesh": [ { "descriptor": "Acetaminophen", "descriptor_ui": "D000082", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Electrophoresis, Capillary", "descriptor_ui": "D019075", "major_topic": false }, { "descriptor": "Energy Metabolism", "descriptor_ui": "D004734", "major_topic": false }, { "descriptor": "Gels", "descriptor_ui": "D005782", "major_topic": false }, { "descriptor": "Hepatocytes", "descriptor_ui": "D022781", "major_topic": true }, { "descriptor": "Human Umbilical Vein Endothelial Cells", "descriptor_ui": "D061307", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "In Vitro Techniques", "descriptor_ui": "D066298", "major_topic": false }, { "descriptor": "Liver", "descriptor_ui": "D008099", "major_topic": true }, { "descriptor": "Mass Spectrometry", "descriptor_ui": "D013058", "major_topic": false }, { "descriptor": "Metabolomics", "descriptor_ui": "D055432", "major_topic": true }, { "descriptor": "Mice, Inbred BALB C", "descriptor_ui": "D008807", "major_topic": false }, { "descriptor": "Models, Anatomic", "descriptor_ui": "D008953", "major_topic": true }, { "descriptor": "Taurocholic Acid", "descriptor_ui": "D013656", "major_topic": false }, { "descriptor": "Toxicity Tests", "descriptor_ui": "D018675", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017", "date_precision": "year", "issue": "4", "normalized_date": "2017", "pages": "445-454", "proceedings_title": null, "publisher": "", "title": "The Journal of toxicological sciences", "volume": "42", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Metabolomics of an in vitro liver model containing primary hepatocytes assembling around an endothelial cell network: comparative study on the metabolic stability and the effect of acetaminophen treatment.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The functions of intracellular signal transduction systems are determined by the temporal behavior of intracellular molecules and their interactions. Of the many dynamical properties of the system, the relationship between the dynamics of upstream molecules and downstream molecules is particularly important. A useful tool in understanding this relationship is a methodology to control the dynamics of intracellular molecules with an extracellular stimulus. However, this is a difficult task because the relationship between the levels of upstream molecules and those of downstream molecules is often not only stochastic, but also time-inhomogeneous, nonlinear, and not one-to-one. In this paper, we present an easy-to-implement model-based control method that makes the target downstream molecule to trace a desired time course by changing the concentration of a controllable upstream molecule. Our method uses predictions from Monte Carlo simulations of the model to decide the strength of the stimulus, while using a particle-based approach to make inferences regarding unobservable states. We applied our method to in silico control problems of insulin-dependent AKT pathway model and EGF-dependent Akt pathway model with system noise. We show that our method can robustly control the dynamics of the intracellular molecules against unknown system noise of various strengths, even in the absence of complete knowledge of the true model of the target system.", "classifications": [ { "id": "Kuroda", "label": "Group Kuroda", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yohei", "last_name": "Murakami", "name": null }, { "creator_type": "author", "first_name": "Masanori", "last_name": "Koyama", "name": null }, { "creator_type": "author", "first_name": "Shigeyuki", "last_name": "Oba", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Kuroda", "name": null }, { "creator_type": "author", "first_name": "Shin", "last_name": "Ishii", "name": null } ], "identifiers": { "doi": { "normalized": "10.2142/biophysico.14.0_29" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "28275530" } }, "mesh": [], "publication": { "conference_name": null, "date": "2017", "date_precision": "year", "issue": "", "normalized_date": "2017", "pages": "29-40", "proceedings_title": null, "publisher": "", "title": "Biophysics and Physicobiology", "volume": "14", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Model-based control of the temporal patterns of intracellular signaling in silico.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Foxp3+ regulatory T cells (Treg cells) modulate the immune system and maintain self-tolerance, but whether they affect haematopoiesis or haematopoietic stem cell (HSC)-mediated reconstitution after transplantation is unclear. Here we show that B-cell lymphopoiesis is impaired in Treg-depleted mice, yet this reduced B-cell lymphopoiesis is rescued by adoptive transfer of affected HSCs or bone marrow cells into Treg-competent recipients. B-cell reconstitution is abrogated in both syngeneic and allogeneic transplantation using Treg-depleted mice as recipients. Treg cells can control physiological IL-7 production that is indispensable for normal B-cell lymphopoiesis and is mainly sustained by a subpopulation of ICAM1+ perivascular stromal cells. Our study demonstrates that Treg cells are important for B-cell differentiation from HSCs by maintaining immunological homoeostasis in the bone marrow microenvironment, both in physiological conditions and after bone marrow transplantation.", "classifications": [ { "id": "Nishikii", "label": "Group Nishikii", "parent": "Shintaku", "type": "group" }, { "id": "Shintaku", "label": "Team Shintaku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Antonio", "last_name": "Pierini", "name": null }, { "creator_type": "author", "first_name": "Hidekazu", "last_name": "Nishikii", "name": null }, { "creator_type": "author", "first_name": "Jeanette", "last_name": "Baker", "name": null }, { "creator_type": "author", "first_name": "Takaharu", "last_name": "Kimura", "name": null }, { "creator_type": "author", "first_name": "Hye-Sook", "last_name": "Kwon", "name": null }, { "creator_type": "author", "first_name": "Yuqiong", "last_name": "Pan", "name": null }, { "creator_type": "author", "first_name": "Yan", "last_name": "Chen", "name": null }, { "creator_type": "author", "first_name": "Maite", "last_name": "Alvarez", "name": null }, { "creator_type": "author", "first_name": "William", "last_name": "Strober", "name": null }, { "creator_type": "author", "first_name": "Andrea", "last_name": "Velardi", "name": null }, { "creator_type": "author", "first_name": "Judith A.", "last_name": "Shizuru", "name": null }, { "creator_type": "author", "first_name": "Joy Y.", "last_name": "Wu", "name": null }, { "creator_type": "author", "first_name": "Shigeru", "last_name": "Chiba", "name": null }, { "creator_type": "author", "first_name": "Robert S.", "last_name": "Negrin", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/ncomms15068" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "28485401" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "B-Lymphocytes", "descriptor_ui": "D001402", "major_topic": false }, { "descriptor": "Bone Marrow", "descriptor_ui": "D001853", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Cellular Microenvironment", "descriptor_ui": "D060833", "major_topic": true }, { "descriptor": "Forkhead Transcription Factors", "descriptor_ui": "D051858", "major_topic": false }, { "descriptor": "Intercellular Adhesion Molecule-1", "descriptor_ui": "D018799", "major_topic": false }, { "descriptor": "Interleukin-7", "descriptor_ui": "D015851", "major_topic": false }, { "descriptor": "Lymphocyte Depletion", "descriptor_ui": "D008212", "major_topic": false }, { "descriptor": "Lymphopoiesis", "descriptor_ui": "D038041", "major_topic": false }, { "descriptor": "Mice, Inbred BALB C", "descriptor_ui": "D008807", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Models, Biological", "descriptor_ui": "D008954", "major_topic": false }, { "descriptor": "Stromal Cells", "descriptor_ui": "D017154", "major_topic": false }, { "descriptor": "T-Lymphocytes, Regulatory", "descriptor_ui": "D050378", "major_topic": false }, { "descriptor": "Transplantation, Homologous", "descriptor_ui": "D014184", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017", "date_precision": "year", "issue": "", "normalized_date": "2017", "pages": "", "proceedings_title": null, "publisher": "", "title": "Nature Communications", "volume": "8", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Foxp3+ regulatory T cells maintain the bone marrow microenvironment for B cell lymphopoiesis.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Under certain circumstances differentiated cells can be reprogrammed to form stem cells in land plants, but only a portion of the cells reprograms successfully. A long-distance inhibitory signal from reprogrammed cells to surrounding cells has been reported in some ferns. Here we show the existence of anisotropic inhibitory signal to regulate stem cell formation in the moss Physcomitrella patens. When single cells were isolated from a gametophore leaf, over 90% of them were reprogrammed to stem cells with characteristic nuclear expansion. By contrast, when two adjacent cells were isolated, the nuclei of both cells expanded, but successful reprogramming of both cells occurred only in approximately one fifth of the pairs. When three aligned cells were isolated, the reprogramming rate of both edge cells decreased with a living middle cell but did not with a dead middle cell. Furthermore, unequal conversion into stem cells was more prominent in cell pairs aligned parallel to the proximal-distal leaf axis than in those perpendicular to the axis. This study gives an insight into the role of the inhibitory signal in development and evolution as well as the efficient stem cell induction from differentiated cells.", "classifications": [ { "id": "Sato", "label": "Group Sato", "parent": "Tsuchiya", "type": "group" }, { "id": "Tsuchiya", "label": "Team Tsuchiya", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yoshikatsu", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Nagisa", "last_name": "Sugimoto", "name": null }, { "creator_type": "author", "first_name": "Tadayoshi", "last_name": "Hirai", "name": null }, { "creator_type": "author", "first_name": "Akihiro", "last_name": "Imai", "name": null }, { "creator_type": "author", "first_name": "Minoru", "last_name": "Kubo", "name": null }, { "creator_type": "author", "first_name": "Yuji", "last_name": "Hiwatashi", "name": null }, { "creator_type": "author", "first_name": "Tomoaki", "last_name": "Nishiyama", "name": null }, { "creator_type": "author", "first_name": "Mitsuyasu", "last_name": "Hasebe", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41598-017-01786-1" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "28507289" } }, "mesh": [ { "descriptor": "Bryopsida", "descriptor_ui": "D019068", "major_topic": false }, { "descriptor": "Cell Communication", "descriptor_ui": "D002450", "major_topic": true }, { "descriptor": "Cellular Reprogramming", "descriptor_ui": "D065150", "major_topic": true }, { "descriptor": "DNA Replication", "descriptor_ui": "D004261", "major_topic": false }, { "descriptor": "Plant Leaves", "descriptor_ui": "D018515", "major_topic": false }, { "descriptor": "Stem Cells", "descriptor_ui": "D013234", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017", "date_precision": "year", "issue": "", "normalized_date": "2017", "pages": "", "proceedings_title": null, "publisher": "", "title": "Scientific Reports", "volume": "7", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Cells reprogramming to stem cells inhibit the reprogramming of adjacent cells in the moss Physcomitrella patens.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Post-translational modification with O-linked beta-N-acetylglucosamine (O-GlcNAc) occurs selectively on serine and/or threonine residues of cytoplasmic and nuclear proteins, and dynamically regulates their molecular functions. Since conventional strategies to evaluate the O-GlcNAcylation level of a specific protein require time-consuming steps, the development of a rapid and easy method for the detection and quantification of an O-GlcNAcylated protein has been a challenging issue. Here, we describe a novel method in which O-GlcNAcylated and non-O-GlcNAcylated forms of proteins are separated by lectin affinity gel electrophoresis using wheat germ agglutinin (WGA), which primarily binds to N-acetylglucosamine residues. Electrophoresis of cell lysates through a gel containing copolymerized WGA selectively induced retardation of the mobility of O-GlcNAcylated proteins, thereby allowing the simultaneous visualization of both the O-GlcNAcylated and the unmodified forms of proteins. This method is therefore useful for the quantitative detection of O-GlcNAcylated proteins.", "classifications": [ { "id": "Takekawa", "label": "Group Takekawa", "parent": "Takekawa", "type": "group" }, { "id": "Takekawa", "label": "Team Takekawa", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yuji", "last_name": "Kubota", "name": null }, { "creator_type": "author", "first_name": "Ko", "last_name": "Fujioka", "name": null }, { "creator_type": "author", "first_name": "Mutsuhiro", "last_name": "Takekawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1371/journal.pone.0180714" }, "pmcid": { "normalized": "PMC5501588" }, "pmid": { "normalized": "28686627" } }, "mesh": [ { "descriptor": "Acetylglucosamine", "descriptor_ui": "D000117", "major_topic": false }, { "descriptor": "Electrophoresis", "descriptor_ui": "D004586", "major_topic": false }, { "descriptor": "Glycosylation", "descriptor_ui": "D006031", "major_topic": false }, { "descriptor": "Protein Processing, Post-Translational", "descriptor_ui": "D011499", "major_topic": true }, { "descriptor": "Proteins", "descriptor_ui": "D011506", "major_topic": false }, { "descriptor": "Wheat Germ Agglutinins", "descriptor_ui": "D014909", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017", "date_precision": "year", "issue": "7", "normalized_date": "2017", "pages": "e0180714", "proceedings_title": null, "publisher": "", "title": "PloS one", "volume": "12", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "WGA-based lectin affinity gel electrophoresis: A novel method for the detection of O-GlcNAc-modified proteins.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Raman spectroscopy, which identifies intrinsic molecular constituents, has a potential for determining myocardial viability under label-free conditions. However, its suitability for evaluating myocardial ischaemia is undetermined. Focusing on cytochromes, i.e., representative molecules reflecting mitochondrial activity, we tested whether Raman spectroscopy is applicable for evaluating myocardial ischaemia especially during early ischaemic phase. We obtained spontaneous Raman spectra of the subepicardial myocardium in the Langendorff-perfused rat heart upon 532-nm excitation before and during the “stopped-flow,” global ischaemia. Semi-quantitative values of the peak intensities at 750 and 1127 cm−1, which reflect reduced cytochromes c and b, increased immediately and progressively after induction of the stopped flow, indicating progressive reduction of the mitochondrial respiration. Such spectral changes emerged before the loss of 1) mitochondrial membrane potentials measured by the fluorescence intensity of tetramethyl rhodamine ethyl ester or 2) staining of the triphenyl tetrazolium chloride dye in the myocardium. The progressive increases in the Raman peaks by stopped flow were significantly retarded by ischaemic preconditioning. Sequential measurements of the peak intensities at 750 and 1127 cm−1 enabled early detection of the myocardial ischaemia based on the mitochondrial functions. These data suggest that Raman spectroscopy offers the potential to evaluate acute ischaemic heart under label-free conditions.", "classifications": [ { "id": "Tanaka", "label": "Group Tanaka", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Suguru", "last_name": "Ohira", "name": null }, { "creator_type": "author", "first_name": "Hideo", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Yoshinori", "last_name": "Harada", "name": null }, { "creator_type": "author", "first_name": "Takeo", "last_name": "Minamikawa", "name": null }, { "creator_type": "author", "first_name": "Yasuaki", "last_name": "Kumamoto", "name": null }, { "creator_type": "author", "first_name": "Satoaki", "last_name": "Matoba", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Yaku", "name": null }, { "creator_type": "author", "first_name": "Tetsuro", "last_name": "Takamatsu", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/srep42401" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "28186163" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Ischemic Preconditioning, Myocardial", "descriptor_ui": "D019157", "major_topic": false }, { "descriptor": "Membrane Potential, Mitochondrial", "descriptor_ui": "D053078", "major_topic": false }, { "descriptor": "Mitochondria", "descriptor_ui": "D008928", "major_topic": false }, { "descriptor": "Myocardial Ischemia", "descriptor_ui": "D017202", "major_topic": false }, { "descriptor": "Myocardium", "descriptor_ui": "D009206", "major_topic": false }, { "descriptor": "Oxygen Consumption", "descriptor_ui": "D010101", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Spectrum Analysis, Raman", "descriptor_ui": "D013059", "major_topic": true }, { "descriptor": "Time-Lapse Imaging", "descriptor_ui": "D059008", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017", "date_precision": "year", "issue": "", "normalized_date": "2017", "pages": "", "proceedings_title": null, "publisher": "", "title": "Scientific Reports", "volume": "7", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Label-free detection of myocardial ischaemia in the perfused rat heart by spontaneous Raman spectroscopy.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Chiral metal catalysts have been widely applied to asymmetric transformations. However, the electronic structure of the catalyst and how it contributes to the activation of the substrate is seldom investigated. Here, we report an empirical approach for providing insights into the catalytic activation process in the distorted Ni(II)-catalysed asymmetric [3+2] cycloaddition of α-ketoesters. We quantitatively characterize the bonding nature of the catalyst by means of electron density distribution analysis, showing that the distortion around the Ni(II) centre makes the dz2 orbital partially ‘naked', wherein the labile acetate ligand is coordinated with electrostatic interaction. The electron-deficient dz2 orbital and the acetate act together to deprotonate the α-ketoester, generating the (Λ)-Ni(II)–enolate. The solid and solution state analyses, together with theoretical calculations, strongly link the electronic structure of the centrochiral octahedral Ni(II) complex and its catalytic activity, depicting a cooperative mechanism of enolate binding and outer sphere hydrogen-bonding activation.", "classifications": [ { "id": "Sodeoka", "label": "Group Sodeoka", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yoshihiro", "last_name": "Sohtome", "name": null }, { "creator_type": "author", "first_name": "Genta", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Atsuya", "last_name": "Muranaka", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Hashizume", "name": null }, { "creator_type": "author", "first_name": "Sylvain", "last_name": "Lectard", "name": null }, { "creator_type": "author", "first_name": "Teruhisa", "last_name": "Tsuchimoto", "name": null }, { "creator_type": "author", "first_name": "Masanobu", "last_name": "Uchiyama", "name": null }, { "creator_type": "author", "first_name": "Mikiko", "last_name": "Sodeoka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/ncomms14875" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "28383035" } }, "mesh": [], "publication": { "conference_name": null, "date": "2017", "date_precision": "year", "issue": "", "normalized_date": "2017", "pages": "", "proceedings_title": null, "publisher": "", "title": "Nature Communications", "volume": "8", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Naked d-orbital in a centrochiral Ni(II) complex as a catalyst for asymmetric [3+2] cycloaddition.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The typical response to the lowering of plasma Na+ concentration and blood pressure in our body involves the release of aldosterone from the adrenal glands, which triggers the reabsorption of sodium in the kidney. Although the effects of aldosterone on this physiological mechanism were extensively studied in the past decades, there are still some aspects to be fully elucidated. In the present study, we propose for the first time a new approach based on Raman spectroscopy to monitor the ionic activity in aldosterone-treated A6 renal epithelial cells. This spectroscopic technique is capable of probing the cells through their thickness in a non-destructive and nimble way. The spectroscopic variations of the Raman bands associated to the O-H stretching of water were correlated to the variations of ionic concentration in the intracellular and extracellular fluids. The increase of Na+ concentration gradients was clearly visualized in the cytosol of aldosterone-treated cells. The enhancement of the Na+ current density induced by aldosterone was estimated from the variation of the ionic chemical potential across the intracellular space. In addition, the variation of the O-H Raman bands of water was used to quantify the cell thickness, which was not affected by aldosterone.", "classifications": [ { "id": "Tanaka", "label": "Group Tanaka", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Leonardo", "last_name": "Puppulin", "name": null }, { "creator_type": "author", "first_name": "Giuseppe", "last_name": "Pezzotti", "name": null }, { "creator_type": "author", "first_name": "Hongxin", "last_name": "Sun", "name": null }, { "creator_type": "author", "first_name": "Shigekuni", "last_name": "Hosogi", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Nakahari", "name": null }, { "creator_type": "author", "first_name": "Toshio", "last_name": "Inui", "name": null }, { "creator_type": "author", "first_name": "Yasuaki", "last_name": "Kumamoto", "name": null }, { "creator_type": "author", "first_name": "Hideo", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Yoshinori", "last_name": "Marunaka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41598-017-03595-y" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "28611439" } }, "mesh": [ { "descriptor": "Aldosterone", "descriptor_ui": "D000450", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Cytosol", "descriptor_ui": "D003600", "major_topic": false }, { "descriptor": "Epithelial Cells", "descriptor_ui": "D004847", "major_topic": false }, { "descriptor": "Ion Transport", "descriptor_ui": "D017136", "major_topic": false }, { "descriptor": "Kidney", "descriptor_ui": "D007668", "major_topic": false }, { "descriptor": "Ouabain", "descriptor_ui": "D010042", "major_topic": false }, { "descriptor": "Sodium", "descriptor_ui": "D012964", "major_topic": false }, { "descriptor": "Spectrum Analysis, Raman", "descriptor_ui": "D013059", "major_topic": false }, { "descriptor": "Xenopus laevis", "descriptor_ui": "D014982", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017", "date_precision": "year", "issue": "", "normalized_date": "2017", "pages": "", "proceedings_title": null, "publisher": "", "title": "Scientific Reports", "volume": "7", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Raman micro-spectroscopy as a viable tool to monitor and estimate the ionic transport in epithelial cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Cysteine hydropersulfide (CysSSH) occurs in abundant quantities in various organisms, yet little is known about its biosynthesis and physiological functions. Extensive persulfide formation is apparent in cysteine-containing proteins in Escherichia coli and mammalian cells and is believed to result from post-translational processes involving hydrogen sulfide-related chemistry. Here we demonstrate effective CysSSH synthesis from the substrate l-cysteine, a reaction catalyzed by prokaryotic and mammalian cysteinyl-tRNA synthetases (CARSs). Targeted disruption of the genes encoding mitochondrial CARSs in mice and human cells shows that CARSs have a crucial role in endogenous CysSSH production and suggests that these enzymes serve as the principal cysteine persulfide synthases in vivo. CARSs also catalyze co-translational cysteine polysulfidation and are involved in the regulation of mitochondrial biogenesis and bioenergetics. Investigating CARS-dependent persulfide production may thus clarify aberrant redox signaling in physiological and pathophysiological conditions, and suggest therapeutic targets based on oxidative stress and mitochondrial dysfunction.", "classifications": [ { "id": "Akaike", "label": "Group Akaike", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Group Nishida", "parent": "Nishida", "type": "group" }, { "id": "Nishimura", "label": "Group Nishimura", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Takaaki", "last_name": "Akaike", "name": null }, { "creator_type": "author", "first_name": "Tomoaki", "last_name": "Ida", "name": null }, { "creator_type": "author", "first_name": "Fan-Yan", "last_name": "Wei", "name": null }, { "creator_type": "author", "first_name": "Motohiro", "last_name": "Nishida", "name": null }, { "creator_type": "author", "first_name": "Yoshito", "last_name": "Kumagai", "name": null }, { "creator_type": "author", "first_name": "Md Morshedul", "last_name": "Alam", "name": null }, { "creator_type": "author", "first_name": "Hideshi", "last_name": "Ihara", "name": null }, { "creator_type": "author", "first_name": "Tomohiro", "last_name": "Sawa", "name": null }, { "creator_type": "author", "first_name": "Tetsuro", "last_name": "Matsunaga", "name": null }, { "creator_type": "author", "first_name": "Shingo", "last_name": "Kasamatsu", "name": null }, { "creator_type": "author", "first_name": "Akiyuki", "last_name": "Nishimura", "name": null }, { "creator_type": "author", "first_name": "Masanobu", "last_name": "Morita", "name": null }, { "creator_type": "author", "first_name": "Kazuhito", "last_name": "Tomizawa", "name": null }, { "creator_type": "author", "first_name": "Akira", "last_name": "Nishimura", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Inaba", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Shima", "name": null }, { "creator_type": "author", "first_name": "Nobuhiro", "last_name": "Tanuma", "name": null }, { "creator_type": "author", "first_name": "Minkyung", "last_name": "Jung", "name": null }, { "creator_type": "author", "first_name": "Shigemoto", "last_name": "Fujii", "name": null }, { "creator_type": "author", "first_name": "Yasuo", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Masaki", "last_name": "Ohmuraya", "name": null }, { "creator_type": "author", "first_name": "Péter", "last_name": "Nagy", "name": null }, { "creator_type": "author", "first_name": "Martin", "last_name": "Feelisch", "name": null }, { "creator_type": "author", "first_name": "Jon M.", "last_name": "Fukuto", "name": null }, { "creator_type": "author", "first_name": "Hozumi", "last_name": "Motohashi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41467-017-01311-y" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "29079736" } }, "mesh": [ { "descriptor": "Amino Acyl-tRNA Synthetases", "descriptor_ui": "D000604", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Computer Simulation", "descriptor_ui": "D003198", "major_topic": false }, { "descriptor": "Cysteine", "descriptor_ui": "D003545", "major_topic": false }, { "descriptor": "Disulfides", "descriptor_ui": "D004220", "major_topic": false }, { "descriptor": "Energy Metabolism", "descriptor_ui": "D004734", "major_topic": true }, { "descriptor": "Escherichia coli", "descriptor_ui": "D004926", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Hydrogen Sulfide", "descriptor_ui": "D006862", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Mitochondria", "descriptor_ui": "D008928", "major_topic": false }, { "descriptor": "Oxidation-Reduction", "descriptor_ui": "D010084", "major_topic": false }, { "descriptor": "Protein Processing, Post-Translational", "descriptor_ui": "D011499", "major_topic": false }, { "descriptor": "Recombinant Proteins", "descriptor_ui": "D011994", "major_topic": false }, { "descriptor": "Sulfhydryl Compounds", "descriptor_ui": "D013438", "major_topic": false }, { "descriptor": "Sulfides", "descriptor_ui": "D013440", "major_topic": false }, { "descriptor": "Tandem Mass Spectrometry", "descriptor_ui": "D053719", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017", "date_precision": "year", "issue": "", "normalized_date": "2017", "pages": "", "proceedings_title": null, "publisher": "", "title": "Nature Communications", "volume": "8", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Cysteinyl-tRNA synthetase governs cysteine polysulfidation and mitochondrial bioenergetics.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Because neutrophil extracellular trap (NET) formation is involved in the pathology of a wide variety of diseases, NET-regulating compounds are expected to be useful for the therapies of these diseases. In this study, we identified sulfasalazine (SSZ) as a potent enhancer of NET formation both in vitro and in vivo. Although SSZ did not increase the amount of ROS generated, it accelerated the generation of ether-linked oxidized phospholipids, such as PE (18;1e/15-HETE) and PC (16;0e/13-HODE). Trolox, but not 2-ME, effectively suppressed lipid oxidation and NET formation that were induced by SSZ. SSZ is known as a potent inducer of ferroptosis in cancer cells by inhibiting xCT, a component of the cystine transporter. However, we found that SSZ accelerated NET formation in an xCT-independent manner. Structure-activity relationship studies revealed that the sulfapyridine moiety of SSZ plays a central role in enhancing NET formation. Furthermore, we found that two additional sulfonamide and sulfone derivatives possess NET-inducing activity by accelerating lipid oxidation. These results indicate that the hyperoxidation of ether-linked phospholipids is a key mechanism for accelerating NET formation.", "classifications": [ { "id": "Sodeoka", "label": "Group Sodeoka", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Satoshi", "last_name": "Yotsumoto", "name": null }, { "creator_type": "author", "first_name": "Yuito", "last_name": "Muroi", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Chiba", "name": null }, { "creator_type": "author", "first_name": "Rio", "last_name": "Ohmura", "name": null }, { "creator_type": "author", "first_name": "Maki", "last_name": "Yoneyama", "name": null }, { "creator_type": "author", "first_name": "Megumi", "last_name": "Magarisawa", "name": null }, { "creator_type": "author", "first_name": "Kosuke", "last_name": "Dodo", "name": null }, { "creator_type": "author", "first_name": "Naoki", "last_name": "Terayama", "name": null }, { "creator_type": "author", "first_name": "Mikiko", "last_name": "Sodeoka", "name": null }, { "creator_type": "author", "first_name": "Ryohei", "last_name": "Aoyagi", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Arita", "name": null }, { "creator_type": "author", "first_name": "Satoko", "last_name": "Arakawa", "name": null }, { "creator_type": "author", "first_name": "Shigeomi", "last_name": "Shimizu", "name": null }, { "creator_type": "author", "first_name": "Masato", "last_name": "Tanaka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41598-017-15668-z" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "29167447" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Apoptosis", "descriptor_ui": "D017209", "major_topic": false }, { "descriptor": "Extracellular Traps", "descriptor_ui": "D065206", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Neutrophils", "descriptor_ui": "D009504", "major_topic": false }, { "descriptor": "NIH 3T3 Cells", "descriptor_ui": "D041681", "major_topic": false }, { "descriptor": "Phospholipid Ethers", "descriptor_ui": "D010742", "major_topic": false }, { "descriptor": "Sulfasalazine", "descriptor_ui": "D012460", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017", "date_precision": "year", "issue": "", "normalized_date": "2017", "pages": "", "proceedings_title": null, "publisher": "", "title": "Scientific Reports", "volume": "7", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Hyperoxidation of ether-linked phospholipids accelerates neutrophil extracellular trap formation.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Helicobacter cinaedi is associated with nosocomial infections. The CRISPR-Cas system provides adaptive immunity against foreign genetic elements. We investigated the CRISPR-Cas system in H. cinaedi to assess the potential of the CRISPR-based microevolution of H. cinaedi strains. A genotyping method based on CRISPR spacer organization was carried out using 42 H. cinaedi strains. The results of sequence analysis showed that the H. cinaedi strains used in this study had two CRISPR loci (CRISPR1 and CRISPR2). The lengths of the consensus direct repeat sequences in CRISPR1 and CRISPR2 were both 36 bp-long, and 224 spacers were found in the 42 H. cinaedi strains. Analysis of the organization and sequence similarity of the spacers of the H. cinaedi strains showed that CRISPR arrays could be divided into 7 different genotypes. Each genotype had a different ancestral spacer, and spacer acquisition/deletion events occurred while isolates were spreading. Spacer polymorphisms of conserved arrays across the strains were instrumental for differentiating closely-related strains collected from the same hospital. MLST had little variability, while the CRISPR sequences showed remarkable diversity. Our data revealed the structural features of H. cinaedi CRISPR loci for the first time. CRISPR sequences constitute a valuable basis for genotyping, provide insights into the divergence and relatedness between closely-related strains, and reflect the microevolutionary process of H. cinaedi.", "classifications": [ { "id": "Akaike", "label": "Group Akaike", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Junko", "last_name": "Tomida", "name": null }, { "creator_type": "author", "first_name": "Yuji", "last_name": "Morita", "name": null }, { "creator_type": "author", "first_name": "Keigo", "last_name": "Shibayama", "name": null }, { "creator_type": "author", "first_name": "Ken", "last_name": "Kikuchi", "name": null }, { "creator_type": "author", "first_name": "Tomohiro", "last_name": "Sawa", "name": null }, { "creator_type": "author", "first_name": "Takaaki", "last_name": "Akaike", "name": null }, { "creator_type": "author", "first_name": "Yoshiaki", "last_name": "Kawamura", "name": null } ], "identifiers": { "doi": { "normalized": "10.1371/journal.pone.0186241" }, "pmcid": { "normalized": "PMC5640232" }, "pmid": { "normalized": "29028814" } }, "mesh": [ { "descriptor": "Clustered Regularly Interspaced Short Palindromic Repeats", "descriptor_ui": "D064112", "major_topic": false }, { "descriptor": "Evolution, Molecular", "descriptor_ui": "D019143", "major_topic": true }, { "descriptor": "Genetic Loci", "descriptor_ui": "D056426", "major_topic": false }, { "descriptor": "Genetic Variation", "descriptor_ui": "D014644", "major_topic": true }, { "descriptor": "Genomics", "descriptor_ui": "D023281", "major_topic": false }, { "descriptor": "Helicobacter", "descriptor_ui": "D016998", "major_topic": false }, { "descriptor": "Multilocus Sequence Typing", "descriptor_ui": "D058885", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017", "date_precision": "year", "issue": "10", "normalized_date": "2017", "pages": "e0186241", "proceedings_title": null, "publisher": "", "title": "PloS one", "volume": "12", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Diversity and microevolution of CRISPR loci in Helicobacter cinaedi.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: Although spermatozoa with normal morphology are assumed to have uniform fertilization ability, recent data show that even normal spermatozoa have considerable variation in their head shape which is associated with differences in fertilization ability. Appropriate quantitative indicators for good sperm morphology, however, remain unidentified. METHODS: Therefore, in an effort to identify such an indicator, we compared the nuclear contour of normal mouse spermatozoa by quantitative multivariate analysis using elliptic Fourier descriptors combined with principal component analysis. The spermatozoa were obtained from different strains and collection sites which have been shown to be associated with different fertilization abilities. RESULTS: We found that the head was 5.7% thinner in spermatozoa from the B6D2F1 (BDF1) strain, known to have a higher fertilization rate, than in those from the C57BL/6N (B6N) strain, which has a lower fertilization rate. Moreover, zona-penetrated spermatozoa in the perivitelline space consistently had 5.4% thinner heads than those isolated from the epididymis before ejaculation. The aspect ratio, which represents the sperm head thinness, uniquely distinguished these sperm populations, confirming its validity as a morphological indicator. DISCUSSION: Because aspect ratio has also been shown to characterize human spermatozoa, this unique morphometric indicator might be applicable to compare normal spermatozoa among multiple patients, which will greatly facilitate and enhance current reproductive technologies.", "classifications": [ { "id": "Fujimoto", "label": "Group Fujimoto", "parent": "Ueda", "type": "group" }, { "id": "Ueda", "label": "Team Ueda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Daisuke", "last_name": "Mashiko", "name": null }, { "creator_type": "author", "first_name": "Masahito", "last_name": "Ikawa", "name": null }, { "creator_type": "author", "first_name": "Koichi", "last_name": "Fujimoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.7717/peerj.3913" }, "pmcid": { "normalized": "PMC5641427" }, "pmid": { "normalized": "29038763" } }, "mesh": [], "publication": { "conference_name": null, "date": "2017", "date_precision": "year", "issue": "", "normalized_date": "2017", "pages": "e3913", "proceedings_title": null, "publisher": "", "title": "PeerJ", "volume": "5", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Mouse spermatozoa with higher fertilization rates have thinner nuclei.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Our current understanding of molecular biology provides a clear picture of how the genome, transcriptome and proteome regulate each other, but how the chemical environment of the cell plays a role in cellular regulation remains much to be studied. Here we show an imaging method using hybrid fluorescence-Raman microscopy that measures the chemical micro-environment associated with protein expression patterns in a living cell. Simultaneous detection of fluorescence and Raman signals, realised by spectrally separating the two modes through the single photon anti-Stokes fluorescence emission of fluorescent proteins, enables the accurate correlation of the chemical fingerprint of a specimen to its physiological state. Subsequent experiments revealed the slight chemical differences that enabled the chemical profiling of mouse embryonic stem cells with and without Oct4 expression. Furthermore, using the fluorescent probe as localisation guide, we successfully analysed the detailed chemical content of cell nucleus and Golgi body. The technique can be further applied to a wide range of biomedical studies for the better understanding of chemical events during biological processes.", "classifications": [ { "id": "Fujita", "label": "Group Fujita", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Liang-da", "last_name": "Chiu", "name": null }, { "creator_type": "author", "first_name": "Taro", "last_name": "Ichimura", "name": null }, { "creator_type": "author", "first_name": "Takumasa", "last_name": "Sekiya", "name": null }, { "creator_type": "author", "first_name": "Hiroaki", "last_name": "Machiyama", "name": null }, { "creator_type": "author", "first_name": "Tomonobu", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Hideaki", "last_name": "Fujita", "name": null }, { "creator_type": "author", "first_name": "Takeaki", "last_name": "Ozawa", "name": null }, { "creator_type": "author", "first_name": "Katsumasa", "last_name": "Fujita", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/srep43569" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "28272392" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Biomarkers", "descriptor_ui": "D015415", "major_topic": false }, { "descriptor": "Gene Expression", "descriptor_ui": "D015870", "major_topic": false }, { "descriptor": "Genes, Reporter", "descriptor_ui": "D017930", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Luminescent Proteins", "descriptor_ui": "D008164", "major_topic": false }, { "descriptor": "Metabolomics", "descriptor_ui": "D055432", "major_topic": true }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Microscopy, Fluorescence", "descriptor_ui": "D008856", "major_topic": true }, { "descriptor": "Molecular Imaging", "descriptor_ui": "D057054", "major_topic": false }, { "descriptor": "Octamer Transcription Factor-3", "descriptor_ui": "D050814", "major_topic": false }, { "descriptor": "Proteomics", "descriptor_ui": "D040901", "major_topic": true }, { "descriptor": "Recombinant Fusion Proteins", "descriptor_ui": "D011993", "major_topic": false }, { "descriptor": "Spectrum Analysis, Raman", "descriptor_ui": "D013059", "major_topic": true }, { "descriptor": "Stem Cells", "descriptor_ui": "D013234", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017", "date_precision": "year", "issue": "", "normalized_date": "2017", "pages": "", "proceedings_title": null, "publisher": "", "title": "Scientific Reports", "volume": "7", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Protein expression guided chemical profiling of living cells by the simultaneous observation of Raman scattering and anti-Stokes fluorescence emission.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: This study characterized the changes in quality and quantity of saliva, and changes in the salivary metabolomic profile, to understand the effects of masticatory stimulation. METHODS: Stimulated and unstimulated saliva samples were collected from 55 subjects and salivary hydrophilic metabolites were comprehensively quantified using capillary electrophoresis-time-of-flight mass spectrometry. RESULTS: In total, 137 metabolites were identified and quantified. The concentrations of 44 metabolites in stimulated saliva were significantly higher than those in unstimulated saliva. Pathway analysis identified the upregulation of the urea cycle and synthesis and degradation pathways of glycine, serine, cysteine and threonine in stimulated saliva. A principal component analysis revealed that the effect of masticatory stimulation on salivary metabolomic profiles was less dependent on sample population sex, age, and smoking. The concentrations of only 1 metabolite in unstimulated saliva, and of 3 metabolites stimulated saliva, showed significant correlation with salivary secretion volume, indicating that the salivary metabolomic profile and salivary secretion volume were independent factors. CONCLUSIONS: Masticatory stimulation affected not only salivary secretion volume, but also metabolite concentration patterns. A low correlation between the secretion volume and these patterns supports the conclusion that the salivary metabolomic profile may be a new indicator to characterize masticatory stimulation.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Nobuyuki", "last_name": "Okuma", "name": null }, { "creator_type": "author", "first_name": "Makiko", "last_name": "Saita", "name": null }, { "creator_type": "author", "first_name": "Noriyuki", "last_name": "Hoshi", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Masaru", "last_name": "Tomita", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Sugimoto", "name": null }, { "creator_type": "author", "first_name": "Katsuhiko", "last_name": "Kimoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1371/journal.pone.0183109" }, "pmcid": { "normalized": "PMC5557591" }, "pmid": { "normalized": "28813487" } }, "mesh": [ { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Electrophoresis, Capillary", "descriptor_ui": "D019075", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mass Spectrometry", "descriptor_ui": "D013058", "major_topic": false }, { "descriptor": "Mastication", "descriptor_ui": "D008409", "major_topic": false }, { "descriptor": "Metabolomics", "descriptor_ui": "D055432", "major_topic": false }, { "descriptor": "Principal Component Analysis", "descriptor_ui": "D025341", "major_topic": false }, { "descriptor": "Saliva", "descriptor_ui": "D012463", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017", "date_precision": "year", "issue": "8", "normalized_date": "2017", "pages": "e0183109", "proceedings_title": null, "publisher": "", "title": "PloS one", "volume": "12", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Effect of masticatory stimulation on the quantity and quality of saliva and the salivary metabolomic profile.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "We studied the anti-inflammatory activity of twelve 5,7-dihydroxyflavone analogues in lipopolysaccharide- (LPS-) stimulated RAW 264.7 macrophages. We found that chrysin (1) and 4'-methoxytricetin (9) showed relatively significant anti-inflammatory activity and low cytotoxicity. Moreover, 1 and 9 recovered the expression levels of iNOS and COX2, as well as those of the intracellular inflammatory mediators IL-1β and IL-6, which were upregulated by LPS stimulation. In addition, 1 and 9 actively regulated the phosphorylation of IκBα, leading to the activation of NFκB. Phosphorylation of Akt and ERK5 (upstream of NFκB) by LPS stimulation was significantly regulated by 1 and 9, as well as by BIX 02189 and LY 294002, which are phosphorylation inhibitors of ERK5 and Akt, respectively. The results suggest that compounds 1 and 9 may suppress the levels of iNOS and COX2 by regulating phosphorylation of Akt, ERK5, and IκBα and thus NFκB-related signaling pathways, resulting in anti-inflammatory effects in the cells. Because 1 and 9 showed low cytotoxicity and regulated both PGE(2) and NO production caused by inflammatory responses, they may hold promise as natural anti-inflammatory agents.", "classifications": [ { "id": "Suzuki", "label": "Group Suzuki", "parent": "Takekawa", "type": "group" }, { "id": "Takekawa", "label": "Team Takekawa", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Atsuyoshi", "last_name": "Nishina", "name": null }, { "creator_type": "author", "first_name": "Kazue", "last_name": "Shimizu", "name": null }, { "creator_type": "author", "first_name": "Mamoru", "last_name": "Koketsu", "name": null }, { "creator_type": "author", "first_name": "Masayuki", "last_name": "Ninomiya", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Hayakawa", "name": null }, { "creator_type": "author", "first_name": "Hirokazu", "last_name": "Kimura", "name": null } ], "identifiers": { "doi": { "normalized": "10.1155/2017/7898973" }, "pmcid": { "normalized": "PMC5429937" }, "pmid": { "normalized": "28539967" } }, "mesh": [], "publication": { "conference_name": null, "date": "2017", "date_precision": "year", "issue": "", "normalized_date": "2017", "pages": "7898973", "proceedings_title": null, "publisher": "", "title": "Evidence-based complementary and alternative medicine : eCAM", "volume": "2017", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "5,7-Dihydroxyflavone Analogues May Regulate Lipopolysaccharide-Induced Inflammatory Responses by Suppressing IκBα-Linked Akt and ERK5 Phosphorylation in RAW 264.7 Macrophages.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Excess production of reactive oxygen species (ROS) caused by hyperglycemia is a major risk factor for heart failure. We previously reported that transient receptor potential canonical 3 (TRPC3) channel mediates pressure overload-induced maladaptive cardiac fibrosis by forming stably functional complex with NADPH oxidase 2 (Nox2). Although TRPC3 has been long suggested to form hetero-multimer channels with TRPC6 and function as diacylglycerol-activated cation channels coordinately, the role of TRPC6 in heart is still obscure. We here demonstrated that deletion of TRPC6 had no impact on pressure overload-induced heart failure despite inhibiting interstitial fibrosis in mice. TRPC6-deficient mouse hearts 1 week after transverse aortic constriction showed comparable increases in fibrotic gene expressions and ROS production but promoted inductions of inflammatory cytokines, compared to wild type hearts. Treatment of TRPC6-deficient mice with streptozotocin caused severe reduction of cardiac contractility with enhancing urinary and cardiac lipid peroxide levels, compared to wild type and TRPC3-deficient mice. Knockdown of TRPC6, but not TRPC3, enhanced basal expression levels of cytokines in rat cardiomyocytes. TRPC6 could interact with Nox2, but the abundance of TRPC6 was inversely correlated with that of Nox2. These results strongly suggest that Nox2 destabilization through disrupting TRPC3-Nox2 complex underlies attenuation of hyperglycemia-induced heart failure by TRPC6.", "classifications": [ { "id": "Nishida", "label": "Group Nishida", "parent": "Nishida", "type": "group" }, { "id": "Nishimura", "label": "Group Nishimura", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Sayaka", "last_name": "Oda", "name": null }, { "creator_type": "author", "first_name": "Takuro", "last_name": "Numaga-Tomita", "name": null }, { "creator_type": "author", "first_name": "Naoyuki", "last_name": "Kitajima", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Toyama", "name": null }, { "creator_type": "author", "first_name": "Eri", "last_name": "Harada", "name": null }, { "creator_type": "author", "first_name": "Tsukasa", "last_name": "Shimauchi", "name": null }, { "creator_type": "author", "first_name": "Akiyuki", "last_name": "Nishimura", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Ishikawa", "name": null }, { "creator_type": "author", "first_name": "Yoshito", "last_name": "Kumagai", "name": null }, { "creator_type": "author", "first_name": "Lutz", "last_name": "Birnbaumer", "name": null }, { "creator_type": "author", "first_name": "Motohiro", "last_name": "Nishida", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41598-017-07903-4" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "28790356" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Diabetes Mellitus, Experimental", "descriptor_ui": "D003921", "major_topic": false }, { "descriptor": "Gene Expression Regulation", "descriptor_ui": "D005786", "major_topic": false }, { "descriptor": "Heart Failure", "descriptor_ui": "D006333", "major_topic": false }, { "descriptor": "Hyperglycemia", "descriptor_ui": "D006943", "major_topic": false }, { "descriptor": "Lipid Peroxides", "descriptor_ui": "D008054", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Myocardial Contraction", "descriptor_ui": "D009200", "major_topic": false }, { "descriptor": "Myocardium", "descriptor_ui": "D009206", "major_topic": false }, { "descriptor": "Myocytes, Cardiac", "descriptor_ui": "D032383", "major_topic": false }, { "descriptor": "NADPH Oxidase 2", "descriptor_ui": "D000074662", "major_topic": false }, { "descriptor": "Primary Cell Culture", "descriptor_ui": "D061251", "major_topic": false }, { "descriptor": "Protein Binding", "descriptor_ui": "D011485", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Reactive Oxygen Species", "descriptor_ui": "D017382", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Streptozocin", "descriptor_ui": "D013311", "major_topic": false }, { "descriptor": "TRPC Cation Channels", "descriptor_ui": "D050052", "major_topic": false }, { "descriptor": "TRPC6 Cation Channel", "descriptor_ui": "D000074287", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017", "date_precision": "year", "issue": "", "normalized_date": "2017", "pages": "", "proceedings_title": null, "publisher": "", "title": "Scientific Reports", "volume": "7", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "TRPC6 counteracts TRPC3-Nox2 protein complex leading to attenuation of hyperglycemia-induced heart failure in mice.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "A 53-year-old man diagnosed with adult T-cell lymphoma (ATL) was treated with mLSG15 chemotherapy and achieved a first complete remission. Subsequently, a liver tumor emerged that was pathologically diagnosed as ATL (first relapse). A second remission was achieved after local irradiation and four cycles of mogamulizumab treatment. The patient received peripheral blood stem cell transplantation (HSCT) from a one haplotype HLA-mismatched daughter after total body irradiation and the administration of fludarabine as a myeloablative conditioning regimen, followed by post-transplant cyclophosphamide. While subsequent acute graft-versus-host disease (GVHD) was never more than Grade I, severe chronic GVHD (cGVHD) developed in the oral cavity and skin that was resistant to escalated doses of cyclosporine and prednisolone. The patient subsequently had a second relapse of ATL as a subcutaneous mass and eventually died of disease progression. Mogamulizumab is a humanized monoclonal IgG that targets CC chemokine receptor 4 (CCR4) and is a key treatment option for relapsed ATL. It reportedly increases the risk of acute GVHD after HSCT due to the depletion of CCR4-positive regulatory T-cells; however, information on its impact on cGVHD is unavailable. Here, we discuss the potential risks and benefits of mogamulizumab, particularly in a haploidentical donor setting during a HSCT for ATL.", "classifications": [ { "id": "Nishikii", "label": "Group Nishikii", "parent": "Shintaku", "type": "group" }, { "id": "Shintaku", "label": "Team Shintaku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Manabu", "last_name": "Kusakabe", "name": null }, { "creator_type": "author", "first_name": "Naoki", "last_name": "Kurita", "name": null }, { "creator_type": "author", "first_name": "Hidekazu", "last_name": "Nishikii", "name": null }, { "creator_type": "author", "first_name": "Rie", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Chikashi", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Yasuhisa", "last_name": "Yokoyama", "name": null }, { "creator_type": "author", "first_name": "Mamiko", "last_name": "Sakata-Yanagimoto", "name": null }, { "creator_type": "author", "first_name": "Naoshi", "last_name": "Obara", "name": null }, { "creator_type": "author", "first_name": "Yuichi", "last_name": "Hasegawa", "name": null }, { "creator_type": "author", "first_name": "Shigeru", "last_name": "Chiba", "name": null } ], "identifiers": { "doi": { "normalized": "10.11406/rinketsu.58.449" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "28592758" } }, "mesh": [ { "descriptor": "Antibodies, Monoclonal, Humanized", "descriptor_ui": "D061067", "major_topic": false }, { "descriptor": "Antineoplastic Combined Chemotherapy Protocols", "descriptor_ui": "D000971", "major_topic": false }, { "descriptor": "Cyclophosphamide", "descriptor_ui": "D003520", "major_topic": false }, { "descriptor": "Fatal Outcome", "descriptor_ui": "D017809", "major_topic": false }, { "descriptor": "Haplotypes", "descriptor_ui": "D006239", "major_topic": false }, { "descriptor": "Hematopoietic Stem Cell Transplantation", "descriptor_ui": "D018380", "major_topic": false }, { "descriptor": "Human T-lymphotropic virus 1", "descriptor_ui": "D015368", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Lymphoma, T-Cell", "descriptor_ui": "D016399", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Transplantation, Homologous", "descriptor_ui": "D014184", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017", "date_precision": "year", "issue": "5", "normalized_date": "2017", "pages": "449-454", "proceedings_title": null, "publisher": "", "title": "[Rinsho ketsueki] The Japanese journal of clinical hematology", "volume": "58", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "[Haploidentical transplantation using post-transplant high-dose cyclophosphamide for adult T-cell lymphoma after mogamulizumab treatment].", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Mitochondrial DNA (mtDNA) is organized in nucleoprotein complexes called mitochondrial nucleoids (mt-nucleoids), which are critical units of mtDNA replication and transmission. In humans, several hundreds of mt-nucleoids exist in a cell. However, how numerous mt-nucleoids are maintained during the cell cycle remains elusive, because cell cycle synchronization procedures affect mtDNA replication. Here, we analyzed regulation of the maintenance of mt-nucleoids in the cell cycle, using a fluorescent cell cycle indicator, Fucci2. Live imaging of mt-nucleoids with higher temporal resolution showed frequent attachment and detachment of mt-nucleoids throughout the cell cycle. TFAM, an mtDNA packaging protein, was involved in the regulation of this dynamic process, which was important for maintaining proper mt-nucleoid number. Both an increase in mt-nucleoid number and activation of mtDNA replication occurred during S phase. To increase mt-nucleoid number, mtDNA replication, but not nuclear DNA replication, was necessary. We propose that these dynamic and regulatory processes in the cell cycle maintain several hundred mt-nucleoids in proliferating cells.", "classifications": [ { "id": "Sato", "label": "Group Sato", "parent": "Tsuchiya", "type": "group" }, { "id": "Tsuchiya", "label": "Team Tsuchiya", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Taeko", "last_name": "Sasaki", "name": null }, { "creator_type": "author", "first_name": "Yoshikatsu", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Tetsuya", "last_name": "Higashiyama", "name": null }, { "creator_type": "author", "first_name": "Narie", "last_name": "Sasaki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41598-017-10843-8" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "28900194" } }, "mesh": [ { "descriptor": "Cell Cycle", "descriptor_ui": "D002453", "major_topic": true }, { "descriptor": "DNA, Mitochondrial", "descriptor_ui": "D004272", "major_topic": false }, { "descriptor": "DNA-Binding Proteins", "descriptor_ui": "D004268", "major_topic": false }, { "descriptor": "Epithelial Cells", "descriptor_ui": "D004847", "major_topic": false }, { "descriptor": "Fluorescent Dyes", "descriptor_ui": "D005456", "major_topic": false }, { "descriptor": "HeLa Cells", "descriptor_ui": "D006367", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Intravital Microscopy", "descriptor_ui": "D000069416", "major_topic": true }, { "descriptor": "Microscopy, Fluorescence", "descriptor_ui": "D008856", "major_topic": false }, { "descriptor": "Mitochondrial Proteins", "descriptor_ui": "D024101", "major_topic": false }, { "descriptor": "Nucleoproteins", "descriptor_ui": "D009698", "major_topic": false }, { "descriptor": "Staining and Labeling", "descriptor_ui": "D013194", "major_topic": false }, { "descriptor": "Transcription Factors", "descriptor_ui": "D014157", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017", "date_precision": "year", "issue": "", "normalized_date": "2017", "pages": "", "proceedings_title": null, "publisher": "", "title": "Scientific Reports", "volume": "7", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Live imaging reveals the dynamics and regulation of mitochondrial nucleoids during the cell cycle in Fucci2-HeLa cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Background and Purpose: Cardiac fibrosis is characterized by an increase in fibroblast proliferation, overproduction of extracellular matrix proteins, and the formation of myofibroblast that express α-smooth muscle actin (α-SMA). Endothelin-1 (ET-1) is involved in the pathogenesis of cardiac fibrosis. Overstimulation of endothelin receptors induced cell proliferation, collagen synthesis, and α-SMA expression in cardiac fibroblasts. Although adenosine was shown to have cardioprotective effects, the molecular mechanisms by which adenosine A(2) receptor inhibit ET-1-induced fibroblast proliferation and α-SMA expression in cardiac fibroblasts are not clearly identified. Experimental Approach: This study aimed at evaluating the mechanisms of cardioprotective effects of adenosine receptor agonist in rat cardiac fibroblast by measurement of cell proliferation, and mRNA and protein levels of α-SMA. Key results: Stimulation of adenosine subtype 2B (A(2B)) receptor resulted in the inhibition of ET-1-induced fibroblast proliferation, and a reduction of ET-1-induced α-SMA expression that is dependent on cAMP/Epac/PI3K/Akt signaling pathways in cardiac fibroblasts. The data in this study confirm a critical role for Epac signaling on A(2B) receptor-mediated inhibition of ET-1-induced cardiac fibrosis via PI3K and Akt activation. Conclusion and Implications: This is the first work reporting a novel signaling pathway for the inhibition of ET-1-induced cardiac fibrosis mediated through the A(2B) receptor. Thus, A(2B) receptor agonists represent a promising perspective as therapeutic targets for the prevention of cardiac fibrosis.", "classifications": [ { "id": "Nishida", "label": "Group Nishida", "parent": "Nishida", "type": "group" }, { "id": "Nishimura", "label": "Group Nishimura", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Sarawuth", "last_name": "Phosri", "name": null }, { "creator_type": "author", "first_name": "Ajaree", "last_name": "Arieyawong", "name": null }, { "creator_type": "author", "first_name": "Kwanchai", "last_name": "Bunrukchai", "name": null }, { "creator_type": "author", "first_name": "Warisara", "last_name": "Parichatikanond", "name": null }, { "creator_type": "author", "first_name": "Akiyuki", "last_name": "Nishimura", "name": null }, { "creator_type": "author", "first_name": "Motohiro", "last_name": "Nishida", "name": null }, { "creator_type": "author", "first_name": "Supachoke", "last_name": "Mangmool", "name": null } ], "identifiers": { "doi": { "normalized": "10.3389/fphar.2017.00428" }, "pmcid": { "normalized": "PMC5492828" }, "pmid": { "normalized": "28713274" } }, "mesh": [], "publication": { "conference_name": null, "date": "2017", "date_precision": "year", "issue": "", "normalized_date": "2017", "pages": "428", "proceedings_title": null, "publisher": "", "title": "Frontiers in pharmacology", "volume": "8", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Stimulation of Adenosine A(2B) Receptor Inhibits Endothelin-1-Induced Cardiac Fibroblast Proliferation and α-Smooth Muscle Actin Synthesis Through the cAMP/Epac/PI3K/Akt-Signaling Pathway.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Raman imaging microscopy is a powerful tool for label-free imaging of biological samples. It has the advantage of measuring the spatial distribution of endogenous proteins and lipids in cells, as well as obtaining chemical information on these endogenous molecules, such as hydrogen bonding and electrostatic interactions. However, because Raman intensity is very weak compared with fluorescence intensity, obtaining a reliable Raman image requires fast acquisition of a Raman image and rejection of background fluorescence. In this chapter, we describe the procedure for obtaining images of the Raman band of interest using a multipoint technique, which is the fast acquisition method for obtaining an image.", "classifications": [ { "id": "Nakabayashi", "label": "Group Nakabayashi", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Shinji", "last_name": "Kajimoto", "name": null }, { "creator_type": "author", "first_name": "Mizuki", "last_name": "Takeuchi", "name": null }, { "creator_type": "author", "first_name": "Takakazu", "last_name": "Nakabayashi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/978-3-319-67358-5_12" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "29080138" } }, "mesh": [ { "descriptor": "Amino Acids", "descriptor_ui": "D000596", "major_topic": false }, { "descriptor": "Culture Media", "descriptor_ui": "D003470", "major_topic": false }, { "descriptor": "HeLa Cells", "descriptor_ui": "D006367", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Hydrogen Bonding", "descriptor_ui": "D006860", "major_topic": false }, { "descriptor": "Lipids", "descriptor_ui": "D008055", "major_topic": false }, { "descriptor": "Nonlinear Optical Microscopy", "descriptor_ui": "D000073758", "major_topic": false }, { "descriptor": "Nucleotides", "descriptor_ui": "D009711", "major_topic": false }, { "descriptor": "Optical Imaging", "descriptor_ui": "D061848", "major_topic": false }, { "descriptor": "Proteins", "descriptor_ui": "D011506", "major_topic": false }, { "descriptor": "Static Electricity", "descriptor_ui": "D055672", "major_topic": false }, { "descriptor": "Time Factors", "descriptor_ui": "D013997", "major_topic": false }, { "descriptor": "Vibration", "descriptor_ui": "D014732", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017", "date_precision": "year", "issue": "", "normalized_date": "2017", "pages": "163-172", "proceedings_title": null, "publisher": "", "title": "Advances in experimental medicine and biology", "volume": "1035", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Raman Imaging Microscopy for Quantitative Analysis of Biological Samples.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Inter-sample comparisons of T-cell receptor (TCR) repertoires are crucial for gaining a better understanding of the immunological states determined by different collections of T cells from different donor sites, cell types, and genetic and pathological backgrounds. For quantitative comparison, most previous studies utilized conventional methods in ecology, which focus on TCR sequences that overlap between pairwise samples. Some recent studies attempted another approach that is categorized into Poisson abundance models using the abundance distribution of observed TCR sequences. However, these methods ignore the details of the measured sequences and are consequently unable to identify sub-repertoires that might have important contributions to the observed inter-sample differences. Moreover, the sparsity of sequence data due to the huge diversity of repertoires hampers the performance of these methods, especially when few overlapping sequences exist. In this paper, we propose a new approach for REpertoire COmparison in Low Dimensions (RECOLD) based on TCR sequence information, which can estimate the low-dimensional structure by embedding the pairwise sequence dissimilarities in high-dimensional sequence space. The inter-sample differences between repertoires are then quantified by information-theoretic measures among the distributions of data estimated in the embedded space. Using datasets of mouse and human TCR repertoires, we demonstrate that RECOLD can accurately identify the inter-sample hierarchical structures, which have a good correspondence with our intuitive understanding about sample conditions. Moreover, for the dataset of transgenic mice that have strong restrictions on the diversity of their repertoires, our estimated inter-sample structure was consistent with the structure estimated by previous methods based on abundance or overlapping sequence information. For the dataset of human healthy donors and Sezary syndrome patients, our method also showed robust estimation performance even under the condition of high sparsity in TCR sequences, while previous studies failed to estimate the structure. In addition, we identified the sequences that contribute to the pairwise-sample differences between the repertoires with the different genetic backgrounds of mice. Such identification of the sequences contributing to variation in immune cell repertoires may provide substantial insight for the development of new immunotherapies and vaccines.", "classifications": [ { "id": "Kobayashi", "label": "Group Kobayashi", "parent": "Wakamoto", "type": "group" }, { "id": "Wakamoto", "label": "Team Wakamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Ryo", "last_name": "Yokota", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Kaminaga", "name": null }, { "creator_type": "author", "first_name": "Tetsuya J.", "last_name": "Kobayashi", "name": null } ], "identifiers": { "doi": { "normalized": "10.3389/fimmu.2017.01500" }, "pmcid": { "normalized": "PMC5694755" }, "pmid": { "normalized": "29187849" } }, "mesh": [], "publication": { "conference_name": null, "date": "2017", "date_precision": "year", "issue": "", "normalized_date": "2017", "pages": "1500", "proceedings_title": null, "publisher": "", "title": "Frontiers in immunology", "volume": "8", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Quantification of Inter-Sample Differences in T-Cell Receptor Repertoires Using Sequence-Based Information.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The subtraction of background components from observed spectra is essential in performing multivariable analysis, frequently applied to Raman spectra of cells. The subtraction procedure, however, is manual and time consuming, especially for big data. Here, we propose an automated method for removing background information from measured spectra of cells, exhibiting the theoretical framework and an experimental application.", "classifications": [ { "id": "Nakabayashi", "label": "Group Nakabayashi", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Tatsuro", "last_name": "Sugawara", "name": null }, { "creator_type": "author", "first_name": "Qi", "last_name": "Yang", "name": null }, { "creator_type": "author", "first_name": "Takakazu", "last_name": "Nakabayashi", "name": null }, { "creator_type": "author", "first_name": "Shin-Ichi", "last_name": "Morita", "name": null } ], "identifiers": { "doi": { "normalized": "10.2116/analsci.33.1323" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "29225218" } }, "mesh": [ { "descriptor": "Algorithms", "descriptor_ui": "D000465", "major_topic": false }, { "descriptor": "Automation", "descriptor_ui": "D001331", "major_topic": false }, { "descriptor": "HeLa Cells", "descriptor_ui": "D006367", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Spectrum Analysis, Raman", "descriptor_ui": "D013059", "major_topic": true }, { "descriptor": "Statistics as Topic", "descriptor_ui": "D013223", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017", "date_precision": "year", "issue": "12", "normalized_date": "2017", "pages": "1323-1325", "proceedings_title": null, "publisher": "", "title": "Analytical sciences : the international journal of the Japan Society for Analytical Chemistry", "volume": "33", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "A Proposal for Automated Background Removal of Bio-Raman Data.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: The kidney is always subjected to high metabolic demand. The aim of this study was to characterize metabolic profiles of a rat model of chronic kidney disease (CKD) with cardiorenal syndrome (CRS) induced by prolonged hypertension. METHODS: We used inbred male Dahl salt-sensitive (DS) rats fed an 8% NaCl diet from six weeks of age (high-salt; HS group) or a 0.3% NaCl diet as controls (low-salt; LS group). We analyzed function, pathology, metabolome, and the gene expression related to energy metabolism of the kidney. RESULTS: DS rats with a high-salt diet showed hypertension at 11 weeks of age and elevated serum levels of creatinine and blood urea nitrogen with heart failure at 21 weeks of age. The fibrotic area in the kidneys increased at 21 weeks of age. In addition, gene expression related to mitochondrial function was largely decreased. The levels of citrate and isocitrate increased and the gene expression of alpha-ketoglutaratedehydrogenase and succinyl-CoA synthetase decreased; these are enzymes that metabolize citrate and isocitrate, respectively. In addition, the levels of succinate and acetyl Co-A, both of which are metabolites of the tricarboxylic acid (TCA) cycle, decreased. CONCLUSIONS: DS rats fed a high-salt diet were deemed a suitable model of CKD with CRS. Gene expression and metabolites related to energy metabolism and mitochondria in the kidney significantly changed in DS rats with hypertension in accordance with the progression of renal injury.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yohei", "last_name": "Tanada", "name": null }, { "creator_type": "author", "first_name": "Junji", "last_name": "Okuda", "name": null }, { "creator_type": "author", "first_name": "Takao", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Eri", "last_name": "Minamino-Muta", "name": null }, { "creator_type": "author", "first_name": "Ichijiro", "last_name": "Murata", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Tetsuo", "last_name": "Shioi", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Kimura", "name": null } ], "identifiers": { "doi": { "normalized": "10.7717/peerj.3352" }, "pmcid": { "normalized": "PMC5444364" }, "pmid": { "normalized": "28560105" } }, "mesh": [], "publication": { "conference_name": null, "date": "2017", "date_precision": "year", "issue": "", "normalized_date": "2017", "pages": "e3352", "proceedings_title": null, "publisher": "", "title": "PeerJ", "volume": "5", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "The metabolic profile of a rat model of chronic kidney disease.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Plant cells are covered with rigid cell walls, yet tip-growing cells can elongate by providing new cell wall material to their apical regions. Studies of the mechanical properties of tip-growing plant cells typically involve measurement of the turgor pressure and stiffness of the cells’ apical regions. These experiments, however, do not address how living tip-growing cells react when they encounter physical obstacles that are not substantially altered by turgor pressure. To investigate this issue, we constructed microfabricated platforms with a series of artificial gaps as small as 1 μm, and examined the capability of tip-growing plant cells, including pollen tubes, root hairs, and moss protonemata, to penetrate into these gaps. The cells were grown inside microfluidic chambers and guided towards the gaps using microdevices customized for each cell type. All types of tip-growing cells could grow through the microgaps with their organelles intact, even though the gaps were much smaller than the cylindrical cell diameter. Our findings reveal the dramatic physiological and developmental flexibility of tip-growing plant cells. The microfluidic platforms designed in this study provide novel tools for the elucidation of the mechanical properties of tip-growing plant cells in extremely small spaces.", "classifications": [ { "id": "Sato", "label": "Group Sato", "parent": "Tsuchiya", "type": "group" }, { "id": "Tsuchiya", "label": "Team Tsuchiya", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Naoki", "last_name": "Yanagisawa", "name": null }, { "creator_type": "author", "first_name": "Nagisa", "last_name": "Sugimoto", "name": null }, { "creator_type": "author", "first_name": "Hideyuki", "last_name": "Arata", "name": null }, { "creator_type": "author", "first_name": "Tetsuya", "last_name": "Higashiyama", "name": null }, { "creator_type": "author", "first_name": "Yoshikatsu", "last_name": "Sato", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/s41598-017-01610-w" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "28469280" } }, "mesh": [ { "descriptor": "Microfluidics", "descriptor_ui": "D044085", "major_topic": false }, { "descriptor": "Organelles", "descriptor_ui": "D015388", "major_topic": false }, { "descriptor": "Plant Cells", "descriptor_ui": "D059828", "major_topic": false }, { "descriptor": "Pollen Tube", "descriptor_ui": "D053205", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017", "date_precision": "year", "issue": "", "normalized_date": "2017", "pages": "", "proceedings_title": null, "publisher": "", "title": "Scientific Reports", "volume": "7", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Capability of tip-growing plant cells to penetrate into extremely narrow gaps.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Small ubiquitin-like modifier (SUMO) is a posttranslational protein modifier that binds target proteins covalently (protein sumoylation) and remarkably alters their functions. Protein sumoylation has been linked to various cellular functions such as cell division, DNA repair, and import of nuclear proteins. Thus, its dysregulation is implicated in diverse human diseases such as neurodegenerative disorders and cancers. We recently found that the kinase activity of MEK proteins, which function as central components of the ERK-MAPK cascade and amplify an extracellular proliferation signal, is negatively regulated by sumoylation. Moreover, the oncogenic activity of Ras is enhanced by the abrogation of MEK-sumoylation in cancer cells. Here, we describe several tools and techniques utilized for the elucidation of the properties of SUMO-MEK in our previous reports. We believe that these methods can be used as robust tools for investigating and understanding the biological roles of various SUMO-modified (sumoylated) proteins.", "classifications": [ { "id": "Takekawa", "label": "Group Takekawa", "parent": "Takekawa", "type": "group" }, { "id": "Takekawa", "label": "Team Takekawa", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yuji", "last_name": "Kubota", "name": null }, { "creator_type": "author", "first_name": "Mutsuhiro", "last_name": "Takekawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/978-1-4939-6424-6_7" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "27924561" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Blotting, Western", "descriptor_ui": "D015153", "major_topic": false }, { "descriptor": "Chlorocebus aethiops", "descriptor_ui": "D002522", "major_topic": false }, { "descriptor": "COS Cells", "descriptor_ui": "D019556", "major_topic": false }, { "descriptor": "Enzyme Assays", "descriptor_ui": "D057075", "major_topic": false }, { "descriptor": "Fibroblasts", "descriptor_ui": "D005347", "major_topic": false }, { "descriptor": "HEK293 Cells", "descriptor_ui": "D057809", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "MAP Kinase Signaling System", "descriptor_ui": "D020935", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mitogen-Activated Protein Kinase Kinases", "descriptor_ui": "D020929", "major_topic": false }, { "descriptor": "Protein Binding", "descriptor_ui": "D011485", "major_topic": false }, { "descriptor": "Protein Processing, Post-Translational", "descriptor_ui": "D011499", "major_topic": false }, { "descriptor": "Recombinant Fusion Proteins", "descriptor_ui": "D011993", "major_topic": false }, { "descriptor": "Sumoylation", "descriptor_ui": "D058207", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017", "date_precision": "year", "issue": "", "normalized_date": "2017", "pages": "99-111", "proceedings_title": null, "publisher": "", "title": "Methods in molecular biology (Clifton, N.J.)", "volume": "1487", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Detection and Functional Analysis of SUMO-Modified MEK.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Cysteine persulfide is an L-cysteine derivative having one additional sulfur atom bound to a cysteinyl thiol group, and it serves as a reactive sulfur species that regulates redox homeostasis in cells. Here, we describe a rapid and efficient method of synthesis of L-cysteine derivatives containing isotopic sulfur atoms and application of this method to a reactive sulfur metabolome. We used bacterial cysteine syntheses to incorporate isotopic sulfur atoms into the sulfhydryl moiety of L-cysteine. We cloned three cysteine synthases-CysE, CysK, and CysM-from the Gram-negative bacterium Salmonella enterica serovar Typhimurium LT2, and we generated their recombinant enzymes. We synthesized (34)S-labeled L-cysteine from O-acetyl-L-serine and (34)S-labeled sodium sulfide as substrates for the CysK or CysM reactions. Isotopic labeling of L-cysteine at both sulfur ((34)S) and nitrogen ((15)N) atoms was also achieved by performing enzyme reactions with (15)N-labeled L-serine, acetyl-CoA, and (34)S-labeled sodium sulfide in the presence of CysE and CysK. The present enzyme systems can be applied to syntheses of a series of L-cysteine derivatives including L-cystine, L-cystine persulfide, S-sulfo-L-cysteine, L-cysteine sulfonate, and L-selenocystine. We also prepared (34)S-labeled N-acetyl-L-cysteine (NAC) by incubating (34)S-labeled L-cysteine with acetyl coenzyme A in test tubes. Tandem mass spectrometric identification of low-molecular-weight thiols after monobromobimane derivatization revealed the endogenous occurrence of NAC in the cultured mammalian cells such as HeLa cells and J774.1 cells. Furthermore, we successfully demonstrated, by using (34)S-labeled NAC, metabolic conversion of NAC to glutathione and its persulfide, via intermediate formation of L-cysteine, in the cells. The approach using isotopic sulfur labeling combined with mass spectrometry may thus contribute to greater understanding of reactive sulfur metabolome and redox biology.", "classifications": [ { "id": "Akaike", "label": "Group Akaike", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Katsuhiko", "last_name": "Ono", "name": null }, { "creator_type": "author", "first_name": "Minkyung", "last_name": "Jung", "name": null }, { "creator_type": "author", "first_name": "Tianli", "last_name": "Zhang", "name": null }, { "creator_type": "author", "first_name": "Hiroyasu", "last_name": "Tsutsuki", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Sezaki", "name": null }, { "creator_type": "author", "first_name": "Hideshi", "last_name": "Ihara", "name": null }, { "creator_type": "author", "first_name": "Fan-Yan", "last_name": "Wei", "name": null }, { "creator_type": "author", "first_name": "Kazuhito", "last_name": "Tomizawa", "name": null }, { "creator_type": "author", "first_name": "Takaaki", "last_name": "Akaike", "name": null }, { "creator_type": "author", "first_name": "Tomohiro", "last_name": "Sawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.freeradbiomed.2017.02.023" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "28189853" } }, "mesh": [ { "descriptor": "Acetylcysteine", "descriptor_ui": "D000111", "major_topic": false }, { "descriptor": "Cysteine", "descriptor_ui": "D003545", "major_topic": false }, { "descriptor": "Cysteine Synthase", "descriptor_ui": "D003547", "major_topic": false }, { "descriptor": "HeLa Cells", "descriptor_ui": "D006367", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Isotope Labeling", "descriptor_ui": "D007553", "major_topic": false }, { "descriptor": "Metabolome", "descriptor_ui": "D055442", "major_topic": true }, { "descriptor": "Oxidation-Reduction", "descriptor_ui": "D010084", "major_topic": false }, { "descriptor": "Salmonella typhimurium", "descriptor_ui": "D012486", "major_topic": false }, { "descriptor": "Sulfhydryl Compounds", "descriptor_ui": "D013438", "major_topic": false }, { "descriptor": "Sulfur", "descriptor_ui": "D013455", "major_topic": false }, { "descriptor": "Sulfur Isotopes", "descriptor_ui": "D013460", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 May", "date_precision": "unknown", "issue": "", "normalized_date": null, "pages": "69-79", "proceedings_title": null, "publisher": "", "title": "Free radical biology & medicine", "volume": "106", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Synthesis of l-cysteine derivatives containing stable sulfur isotopes and application of this synthesis to reactive sulfur metabolome.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "In article number 1600394, Almira Kurbangalieva, Katsunori Tanaka, and co‐workers at the RIKEN Biofunctional Synthetic Chemistry Laboratory develop a way to engineer glycan complexes—heterogeneous clusters of sugar chains attached to proteins or lipids—in a way that allows the molecules to be transported preferentially to specific organs of the body through pattern recognition mechanisms, depending on the sugar chains contained in the cluster. [Image: see text]", "classifications": [ { "id": "Suzuki", "label": "Group Suzuki", "parent": "Takekawa", "type": "group" }, { "id": "Takekawa", "label": "Team Takekawa", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Toru", "last_name": "Hanamura", "name": null }, { "creator_type": "author", "first_name": "Tokiko", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Toshiharu", "last_name": "Kanai", "name": null }, { "creator_type": "author", "first_name": "Kazuma", "last_name": "Maeno", "name": null }, { "creator_type": "author", "first_name": "Yasuyo", "last_name": "Shimojo", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Uehara", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Shin-Ichi", "last_name": "Hayashi", "name": null }, { "creator_type": "author", "first_name": "Ken-Ichi", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Liliya", "last_name": "Latypova", "name": null }, { "creator_type": "author", "first_name": "Regina", "last_name": "Sibgatullina", "name": null }, { "creator_type": "author", "first_name": "Akihiro", "last_name": "Ogura", "name": null }, { "creator_type": "author", "first_name": "Katsumasa", "last_name": "Fujiki", "name": null }, { "creator_type": "author", "first_name": "Alsu", "last_name": "Khabibrakhmanova", "name": null }, { "creator_type": "author", "first_name": "Tsuyoshi", "last_name": "Tahara", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Nozaki", "name": null }, { "creator_type": "author", "first_name": "Sayaka", "last_name": "Urano", "name": null }, { "creator_type": "author", "first_name": "Kazuki", "last_name": "Tsubokura", "name": null }, { "creator_type": "author", "first_name": "Hirotaka", "last_name": "Onoe", "name": null }, { "creator_type": "author", "first_name": "Yasuyoshi", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Almira", "last_name": "Kurbangalieva", "name": null }, { "creator_type": "author", "first_name": "Katsunori", "last_name": "Tanaka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/advs.201770006" }, "pmcid": { "normalized": "PMC4864168" }, "pmid": { "normalized": "27139182" } }, "mesh": [ { "descriptor": "3-Hydroxysteroid Dehydrogenases", "descriptor_ui": "D015096", "major_topic": false }, { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Aged, 80 and over", "descriptor_ui": "D000369", "major_topic": false }, { "descriptor": "Biomarkers, Tumor", "descriptor_ui": "D014408", "major_topic": true }, { "descriptor": "Breast Neoplasms", "descriptor_ui": "D001943", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Gene Expression", "descriptor_ui": "D015870", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Immunohistochemistry", "descriptor_ui": "D007150", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Neoplasm Grading", "descriptor_ui": "D060787", "major_topic": false }, { "descriptor": "Neoplasm Metastasis", "descriptor_ui": "D009362", "major_topic": false }, { "descriptor": "Neoplasm Staging", "descriptor_ui": "D009367", "major_topic": false }, { "descriptor": "Prognosis", "descriptor_ui": "D011379", "major_topic": false }, { "descriptor": "Receptors, Estrogen", "descriptor_ui": "D011960", "major_topic": false }, { "descriptor": "Survival Analysis", "descriptor_ui": "D016019", "major_topic": false }, { "descriptor": "Tumor Burden", "descriptor_ui": "D047368", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Feb", "date_precision": "unknown", "issue": "2", "normalized_date": null, "pages": "n/a", "proceedings_title": null, "publisher": "", "title": "Advanced Science", "volume": "4", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Pattern Recognition: Sequential Double “Clicks” toward Structurally Well‐Defined Heterogeneous N‐Glycoclusters: The Importance of Cluster Heterogeneity on Pattern Recognition In Vivo (Adv. Sci. 2/2017).", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "p62/sequestosome 1 (p62) is a multi-domain protein that functions as a receptor for ubiquitinated targets in the selective autophagy and serves as a scaffold in various signaling cascades. p62 have been reported to be up-regulated in several human malignancies, but the biological roles and significance of p62 are still poorly understood in colorectal carcinoma. We immunohistochemically evaluated p62 in 118 colorectal adenocarcinoma and 28 colorectal adenoma cases. We used four colon carcinoma cells (HCT8, HT29, COLO320, and SW480) in the in vitro studies. p62 immunoreactivity was detected in 11% of colorectal adenoma cases and 31% of adenocarcinoma cases, while it was negligible in the normal epithelium. The immunohistochemical p62 status was significantly associated with synchronous liver metastasis, and it turned out to be an independent adverse prognostic factor in colorectal cancer patients. Following in vitro studies revealed that HCT8 and HT29 cells transfected with p62-specific siRNA showed significantly decreased cell proliferation activity, whereas COLO320 and SW480 cells transfected with p62 expression plasmid showed significantly increased cell proliferation activity. The p62-mediated cell proliferation was not associated with the autophagy activity. These findings suggest that p62 promotes the cell proliferation mainly as a scaffold protein, and that the p62 status is a potent prognostic factor in colorectal carcinoma patients.", "classifications": [ { "id": "Suzuki", "label": "Group Suzuki", "parent": "Takekawa", "type": "group" }, { "id": "Takekawa", "label": "Team Takekawa", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Shun", "last_name": "Nakayama", "name": null }, { "creator_type": "author", "first_name": "Hideaki", "last_name": "Karasawa", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Shinichi", "last_name": "Yabuuchi", "name": null }, { "creator_type": "author", "first_name": "Kiyoshi", "last_name": "Takagi", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Aizawa", "name": null }, { "creator_type": "author", "first_name": "Yoshiaki", "last_name": "Onodera", "name": null }, { "creator_type": "author", "first_name": "Yasuhiro", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Mika", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Fumiyoshi", "last_name": "Fujishima", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Takanori", "last_name": "Morikawa", "name": null }, { "creator_type": "author", "first_name": "Tomohiko", "last_name": "Sase", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Naitoh", "name": null }, { "creator_type": "author", "first_name": "Michiaki", "last_name": "Unno", "name": null }, { "creator_type": "author", "first_name": "Hironobu", "last_name": "Sasano", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/cam4.1093" }, "pmcid": { "normalized": "PMC5463080" }, "pmid": { "normalized": "28544335" } }, "mesh": [ { "descriptor": "Adenocarcinoma", "descriptor_ui": "D000230", "major_topic": false }, { "descriptor": "Adenoma", "descriptor_ui": "D000236", "major_topic": false }, { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Cell Proliferation", "descriptor_ui": "D049109", "major_topic": false }, { "descriptor": "Colorectal Neoplasms", "descriptor_ui": "D015179", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Neoplasm Staging", "descriptor_ui": "D009367", "major_topic": false }, { "descriptor": "Plasmids", "descriptor_ui": "D010957", "major_topic": false }, { "descriptor": "Prognosis", "descriptor_ui": "D011379", "major_topic": false }, { "descriptor": "RNA, Messenger", "descriptor_ui": "D012333", "major_topic": false }, { "descriptor": "Sequestosome-1 Protein", "descriptor_ui": "D000071456", "major_topic": false }, { "descriptor": "Transfection", "descriptor_ui": "D014162", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Jun", "date_precision": "unknown", "issue": "6", "normalized_date": null, "pages": "1264-1274", "proceedings_title": null, "publisher": "", "title": "Cancer medicine", "volume": "6", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "p62/sequestosome 1 in human colorectal carcinoma as a potent prognostic predictor associated with cell proliferation.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Surviving Purkinje fibers in myocardial infarct are regarded as an important substrate in arrhythmogenesis. However, poorly understood are functional properties of Purkinje fibers in the infarcted heart. We sought to visualize intracellular Ca2+ ([Ca2+]i) dynamics of Purkinje fiber networks in the mouse myocardial infarct. Using 3- to 4-day-old or 7- to 9-day-old infarcted hearts after the left coronary-artery ligation corresponding, respectively, to acute or healing phase, we conducted rapid fluo4-fluorescence imaging on the endocardial surface of the left ventricular septum by macro-zoom fluorescence microscopy and rapid-scanning confocal microscopy. In contrast with the intact heart, where uniform Ca2+ transients propagated rapidly, the infarcted heart exhibited slow, non-uniform impulse propagations. On confocal microscopy, Purkinje fibers in the peri-infarct zone exhibited non-uniform [Ca2+]i dynamics: beat-to-beat alternans of the Ca2+ transient amplitude in and among the individual fibers, whereas the intact fibers exhibited uniform Ca2+ transients. Such non-uniform [Ca2+]i dynamics were more conspicuous in the acute infarcted hearts than in the healing ones. In accordance with [Ca2+]i dynamics, fixed fluo4-loaded heart preparations exhibited definitive connexin-40 plaques in the peri-infarct Purkinje fibers, whereas the subjacent myocardium presented coagulative necrosis and granulation tissues, respectively. The surviving Purkinje fibers in the peri-infarct zone exhibited non-uniform [Ca2+]i dynamics, which may lead to arrhythmogenesis.", "classifications": [ { "id": "Tanaka", "label": "Group Tanaka", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Taka-aki", "last_name": "Matsuyama", "name": null }, { "creator_type": "author", "first_name": "Hideo", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Hatsue", "last_name": "Ishibashi-Ueda", "name": null }, { "creator_type": "author", "first_name": "Tetsuro", "last_name": "Takamatsu", "name": null } ], "identifiers": { "doi": { "normalized": "10.1369/0022155417730280" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "28903013" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Calcium", "descriptor_ui": "D002118", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Microscopy, Confocal", "descriptor_ui": "D018613", "major_topic": false }, { "descriptor": "Microscopy, Fluorescence", "descriptor_ui": "D008856", "major_topic": false }, { "descriptor": "Myocardial Infarction", "descriptor_ui": "D009203", "major_topic": false }, { "descriptor": "Myocardium", "descriptor_ui": "D009206", "major_topic": false }, { "descriptor": "Purkinje Fibers", "descriptor_ui": "D011690", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Nov", "date_precision": "unknown", "issue": "11", "normalized_date": null, "pages": "655-667", "proceedings_title": null, "publisher": "", "title": "Journal of Histochemistry and Cytochemistry", "volume": "65", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Spatiotemporally Non-Uniform Ca2+ Dynamics of Cardiac Purkinje Fibers in Mouse Myocardial Infarct.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Uncoupling protein 1 (UCP1) plays a central role in nonshivering thermogenesis in brown fat; however, its role in beige fat remains unclear. Here we report a robust UCP1-independent thermogenic mechanism in beige fat that involves enhanced ATP-dependent Ca(2+) cycling by sarco/endoplasmic reticulum Ca(2+)-ATPase 2b (SERCA2b) and ryanodine receptor 2 (RyR2). Inhibition of SERCA2b impairs UCP1-independent beige fat thermogenesis in humans and mice as well as in pigs, a species that lacks a functional UCP1 protein. Conversely, enhanced Ca(2+) cycling by activation of alpha1- and/or beta3-adrenergic receptors or the SERCA2b-RyR2 pathway stimulates UCP1-independent thermogenesis in beige adipocytes. In the absence of UCP1, beige fat dynamically expends glucose through enhanced glycolysis, tricarboxylic acid metabolism and pyruvate dehydrogenase activity for ATP-dependent thermogenesis through the SERCA2b pathway; beige fat thereby functions as a 'glucose sink' and improves glucose tolerance independently of body weight loss. Our study uncovers a noncanonical thermogenic mechanism through which beige fat controls whole-body energy homeostasis via Ca(2+) cycling.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Kenji", "last_name": "Ikeda", "name": null }, { "creator_type": "author", "first_name": "Qianqian", "last_name": "Kang", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Yoneshiro", "name": null }, { "creator_type": "author", "first_name": "Joao Paulo", "last_name": "Camporez", "name": null }, { "creator_type": "author", "first_name": "Hiroko", "last_name": "Maki", "name": null }, { "creator_type": "author", "first_name": "Mayu", "last_name": "Homma", "name": null }, { "creator_type": "author", "first_name": "Kosaku", "last_name": "Shinoda", "name": null }, { "creator_type": "author", "first_name": "Yong", "last_name": "Chen", "name": null }, { "creator_type": "author", "first_name": "Xiaodan", "last_name": "Lu", "name": null }, { "creator_type": "author", "first_name": "Pema", "last_name": "Maretich", "name": null }, { "creator_type": "author", "first_name": "Kazuki", "last_name": "Tajima", "name": null }, { "creator_type": "author", "first_name": "Kolapo M.", "last_name": "Ajuwon", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Shingo", "last_name": "Kajimura", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/nm.4429" }, "pmcid": { "normalized": "PMC5727902" }, "pmid": { "normalized": "29131158" } }, "mesh": [ { "descriptor": "Adipose Tissue, Beige", "descriptor_ui": "D000069796", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Animals, Newborn", "descriptor_ui": "D000831", "major_topic": false }, { "descriptor": "Calcium", "descriptor_ui": "D002118", "major_topic": false }, { "descriptor": "Calcium Signaling", "descriptor_ui": "D020013", "major_topic": false }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Glucose", "descriptor_ui": "D005947", "major_topic": false }, { "descriptor": "HEK293 Cells", "descriptor_ui": "D057809", "major_topic": false }, { "descriptor": "Homeostasis", "descriptor_ui": "D006706", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Sarcoplasmic Reticulum Calcium-Transporting ATPases", "descriptor_ui": "D053498", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Swine", "descriptor_ui": "D013552", "major_topic": false }, { "descriptor": "Thermogenesis", "descriptor_ui": "D022722", "major_topic": false }, { "descriptor": "Uncoupling Protein 1", "descriptor_ui": "D000071256", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Dec", "date_precision": "unknown", "issue": "12", "normalized_date": null, "pages": "1454-1465", "proceedings_title": null, "publisher": "", "title": "Nature medicine", "volume": "23", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "UCP1-independent signaling involving SERCA2b-mediated calcium cycling regulates beige fat thermogenesis and systemic glucose homeostasis.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "We present a full account of our synthetic studies on the racemic DEFGH-ring moiety of physalins, featuring domino ring transformation of a tricyclic key intermediate. We also report the results of a detailed mechanistic examination of the domino ring transformation, as well as a reoptimization of the 2,3-Wittig rearrangement and methylation steps. Furthermore, we have newly established a method for the preparation of an optically active synthetic intermediate by enzymatic kinetic resolution. Our work provides access to both natural and nonnatural right-side physalin structures.", "classifications": [ { "id": "Sodeoka", "label": "Group Sodeoka", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Masaki", "last_name": "Morita", "name": null }, { "creator_type": "author", "first_name": "Shuntaro", "last_name": "Kojima", "name": null }, { "creator_type": "author", "first_name": "Megumi", "last_name": "Ohkubo", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Koshino", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Hashizume", "name": null }, { "creator_type": "author", "first_name": "Go", "last_name": "Hirai", "name": null }, { "creator_type": "author", "first_name": "Keiji", "last_name": "Maruoka", "name": null }, { "creator_type": "author", "first_name": "Mikiko", "last_name": "Sodeoka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/ijch.201600110" }, "pmcid": { "normalized": "PMC5467525" }, "pmid": { "normalized": "28659646" } }, "mesh": [], "publication": { "conference_name": null, "date": "2017 Apr", "date_precision": "unknown", "issue": "3-4", "normalized_date": null, "pages": "309-318", "proceedings_title": null, "publisher": "", "title": "Israel journal of chemistry", "volume": "57", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Synthesis of the Right-Side Structure of Type B Physalins.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: Changes of epidermal calcium ion concentration are involved in regulation of barrier homeostasis and keratinocyte differentiation. Moreover, intracellular calcium dynamics might play a role in skin sensation. But, although calcium dynamics of cultured keratinocytes in response to mechanical stresses has been well studied, calcium propagation in stimulated human epidermis is still poorly understood. OBJECTIVE: The aim of this study was to demonstrate a novel method for real-time measurement of calcium dynamics in response to point stimulation of human epidermis at the single-cell level. METHODS: We examined calcium propagation in cross-sectional samples of living human epidermis ex vivo, as well as in cultured human keratinocytes, by means of two-photon microscopy after stimulating cells in stratum granulosum with the emission laser of a two-photon microscope. RESULTS: Cells in different epidermal layers showed different responses, and those in stratum basale showed the greatest elevation of intracellular calcium. Calcium propagation in epidermis was inhibited in the presence of apyrase (which degrades adenosine triphosphate; ATP) or gap-junction blockers. In cultured keratinocytes, on the other hand, calcium propagated in a simple concentric wave-like manner from the stimulation site, and propagation was strongly suppressed by apyrase. CONCLUSION: Our results suggested that ATP and gap junctions play important roles in calcium propagation induced by point laser stimulation of the uppermost layer of epidermis. Our method should be broadly useful to study calcium dynamics, epidermal physiological mechanisms, and mechanisms of skin sensation at the single-cell level.", "classifications": [ { "id": "Nagayama", "label": "Group Nagayama", "parent": "Fujiwara", "type": "group" }, { "id": "Fujiwara", "label": "Team Fujiwara", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Junichi", "last_name": "Kumamoto", "name": null }, { "creator_type": "author", "first_name": "Makiko", "last_name": "Goto", "name": null }, { "creator_type": "author", "first_name": "Masaharu", "last_name": "Nagayama", "name": null }, { "creator_type": "author", "first_name": "Mitsuhiro", "last_name": "Denda", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.jdermsci.2017.01.002" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "28119009" } }, "mesh": [ { "descriptor": "Adenosine Triphosphate", "descriptor_ui": "D000255", "major_topic": false }, { "descriptor": "Apyrase", "descriptor_ui": "D001081", "major_topic": false }, { "descriptor": "Calcium", "descriptor_ui": "D002118", "major_topic": false }, { "descriptor": "Calcium Signaling", "descriptor_ui": "D020013", "major_topic": true }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Epidermis", "descriptor_ui": "D004817", "major_topic": false }, { "descriptor": "Gap Junctions", "descriptor_ui": "D017629", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Keratinocytes", "descriptor_ui": "D015603", "major_topic": false }, { "descriptor": "Lasers", "descriptor_ui": "D007834", "major_topic": false }, { "descriptor": "Microscopy, Confocal", "descriptor_ui": "D018613", "major_topic": false }, { "descriptor": "Microscopy, Fluorescence, Multiphoton", "descriptor_ui": "D036641", "major_topic": false }, { "descriptor": "Models, Biological", "descriptor_ui": "D008954", "major_topic": false }, { "descriptor": "Tight Junctions", "descriptor_ui": "D019108", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Apr", "date_precision": "unknown", "issue": "1", "normalized_date": null, "pages": "13-20", "proceedings_title": null, "publisher": "", "title": "Journal of dermatological science", "volume": "86", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Real-time imaging of human epidermal calcium dynamics in response to point laser stimulation.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "It is well known that comedo necrosis is closely associated with an aggressive phenotype of ductal carcinoma in situ (DCIS) of human breast, but its molecular mechanisms remain largely unclear. Therefore, in this study, we first examined the gene expression profile of comedo DCIS based on microarray data and identified CYC1 as a gene associated with comedo necrosis. Cytochrome c1 (CYC1) is a subunit of complex III in the mitochondrial oxidative phosphorylation that is involved in energy production. However, the significance of CYC1 has not yet been examined in DCIS. We therefore immunolocalized CYC1 in 47 DCIS cases. CYC1 immunoreactivity was detected in 40% of DCIS cases, and the immunohistochemical CYC1 status was significantly associated with tumor size, nuclear grade, comedo necrosis, van Nuys classification, and Ki-67 labeling index. Subsequent in vitro studies indicated that CYC1 was significantly associated with mitochondrial membrane potential in MCF10DCIS.com DCIS cells. Moreover, CYC1 significantly promoted proliferation activity of MCF10DCIS.com cells and the cells transfected with CYC1 siRNA decreased pro-apoptotic caspase 3 activity under hypoxic or anoxic conditions. Considering that the center of DCIS is poorly oxygenated, these results indicate that CYC1 plays important roles in cell proliferation and comedo necrosis through the elevated oxidative phosphorylation activity in human DCIS.", "classifications": [ { "id": "Suzuki", "label": "Group Suzuki", "parent": "Takekawa", "type": "group" }, { "id": "Takekawa", "label": "Team Takekawa", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Mayuko", "last_name": "Chishiki", "name": null }, { "creator_type": "author", "first_name": "Kiyoshi", "last_name": "Takagi", "name": null }, { "creator_type": "author", "first_name": "Ai", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Yasuhiro", "last_name": "Miki", "name": null }, { "creator_type": "author", "first_name": "Yuta", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Akiko", "last_name": "Ebata", "name": null }, { "creator_type": "author", "first_name": "Yukiko", "last_name": "Shibahara", "name": null }, { "creator_type": "author", "first_name": "Mika", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Takanori", "last_name": "Ishida", "name": null }, { "creator_type": "author", "first_name": "Hironobu", "last_name": "Sasano", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Suzuki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/cas.13251" }, "pmcid": { "normalized": "PMC5497933" }, "pmid": { "normalized": "28394473" } }, "mesh": [ { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Aged, 80 and over", "descriptor_ui": "D000369", "major_topic": false }, { "descriptor": "Breast Neoplasms", "descriptor_ui": "D001943", "major_topic": false }, { "descriptor": "Carcinoma, Intraductal, Noninfiltrating", "descriptor_ui": "D002285", "major_topic": false }, { "descriptor": "Cytochromes c1", "descriptor_ui": "D003575", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Immunoblotting", "descriptor_ui": "D015151", "major_topic": false }, { "descriptor": "Immunohistochemistry", "descriptor_ui": "D007150", "major_topic": false }, { "descriptor": "Laser Capture Microdissection", "descriptor_ui": "D061346", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Necrosis", "descriptor_ui": "D009336", "major_topic": false }, { "descriptor": "Oligonucleotide Array Sequence Analysis", "descriptor_ui": "D020411", "major_topic": false }, { "descriptor": "Real-Time Polymerase Chain Reaction", "descriptor_ui": "D060888", "major_topic": false }, { "descriptor": "Transcriptome", "descriptor_ui": "D059467", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Jul", "date_precision": "unknown", "issue": "7", "normalized_date": null, "pages": "1510-1519", "proceedings_title": null, "publisher": "", "title": "Cancer science", "volume": "108", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Cytochrome c1 in ductal carcinoma in situ of breast associated with proliferation and comedo necrosis.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "A specific subtype of non-small-cell lung cancer (NSCLC) characterized with an EML4-ALK fusion gene, which drives constitutive oncogenic activation of anaplastic lymphoma kinase (ALK), shows a good clinical response to ALK inhibitors. We have reported multiple examples implying the biological significance of methylation on non-histone proteins including oncogenic kinases in human carcinogenesis. Through the process to search substrates for various methyltransferases using an in vitro methyltransferase assay, we found that a lysine methyltransferase, SET and MYND domain-containing 2 (SMYD2), could methylate lysine residues 1451, 1455, and 1610 in ALK protein. Knockdown of SMYD2 as well as treatment with a SMYD2 inhibitor in two NSCLC cell lines with an EML4-ALK gene significantly attenuated the phosphorylation levels of the EML4-ALK protein. Substitutions of each of these three lysine residues to an alanine partially or almost completely diminished in vitro methylation of ALK. In addition, we found that exogenous introduction of EML4-ALK protein with the substitution of lysine 1610 to an alanine in these two cell lines reduced the phosphorylation levels of AKT, one of the downstream oncogenic molecules in the EML4-ALK pathway, and suppressed the growth of the two cell lines. We further showed that the combination of a SMYD2 inhibitor and an ALK inhibitor additively suppressed the growth of these two NSCLC cells, compared with single-agent treatment. Our results shed light on a novel mechanism that modulates the kinase activity of the ALK fused gene product and imply that SMYD2-mediated ALK methylation might be a promising target for development of a novel class of treatment for tumors with the ALK fused gene.", "classifications": [ { "id": "Hamamoto", "label": "Group Hamamoto", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Rui", "last_name": "Wang", "name": null }, { "creator_type": "author", "first_name": "Xiaolan", "last_name": "Deng", "name": null }, { "creator_type": "author", "first_name": "Yuichiro", "last_name": "Yoshioka", "name": null }, { "creator_type": "author", "first_name": "Theodore", "last_name": "Vougiouklakis", "name": null }, { "creator_type": "author", "first_name": "Jae-Hyun", "last_name": "Park", "name": null }, { "creator_type": "author", "first_name": "Takehiro", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Naoshi", "last_name": "Dohmae", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Ueda", "name": null }, { "creator_type": "author", "first_name": "Ryuji", "last_name": "Hamamoto", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Nakamura", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/cas.13245" }, "pmcid": { "normalized": "PMC5480063" }, "pmid": { "normalized": "28370702" } }, "mesh": [ { "descriptor": "Anaplastic Lymphoma Kinase", "descriptor_ui": "D000077548", "major_topic": false }, { "descriptor": "Apoptosis", "descriptor_ui": "D017209", "major_topic": false }, { "descriptor": "Carcinoma, Non-Small-Cell Lung", "descriptor_ui": "D002289", "major_topic": false }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Cell Proliferation", "descriptor_ui": "D049109", "major_topic": false }, { "descriptor": "Histone-Lysine N-Methyltransferase", "descriptor_ui": "D011495", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Lung Neoplasms", "descriptor_ui": "D008175", "major_topic": false }, { "descriptor": "Methylation", "descriptor_ui": "D008745", "major_topic": false }, { "descriptor": "Oncogene Proteins, Fusion", "descriptor_ui": "D015514", "major_topic": false }, { "descriptor": "Phosphorylation", "descriptor_ui": "D010766", "major_topic": false }, { "descriptor": "Receptor Protein-Tyrosine Kinases", "descriptor_ui": "D020794", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Jun", "date_precision": "unknown", "issue": "6", "normalized_date": null, "pages": "1203-1209", "proceedings_title": null, "publisher": "", "title": "Cancer science", "volume": "108", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Effects of SMYD2-mediated EML4-ALK methylation on the signaling pathway and growth in non-small-cell lung cancer cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Although higher circulating levels of oestrogen are related to postmenopausal breast cancer risk, limited information is available regarding effects of diet on endogenous oestrogen. Thus, we examined associations between macronutrient intakes and serum oestrogen with consideration of polymorphisms in oestrogen-metabolising genes. In this cross-sectional study, 784 naturally menopaused Japanese women aged 47-69 years were selected from participants of the Japan Multi-Institutional Collaborative Cohort Study. We documented dietary intakes, measured serum concentrations of oestrone (E1) and oestradiol (E2) and genotyped polymorphisms in oestrogen-metabolising CYP19A1 (rs4441215 and rs936306) and HSD17B1 (rs605059) genes. Trends and interactions were examined using linear regression models. In addition, we calculated the ratios of the oestrogen concentrations of the second to the highest quartiles (Q2-Q4) of dietary intake to those of the lowest quartiles (Q1). After adjustment for potential confounders, E2 was significantly associated with intake of carbohydrate and noodles; ratios of Q4 v. Q1 were 1.15 (95 % CI 1.04, 1.28) and 1.15 (95 % CI 1.04, 1.26), respectively. In contrast, E2 levels were inversely associated with intake of total energy, SFA and n-3 highly unsaturated fatty acids (n-3 HUFA); ratios of Q4 v. Q1 were 0.90 (95 % CI 0.82, 0.99), 0.89 (95 % CI 0.81, 0.98) and 0.91 (95 % CI 0.83, 1.00), respectively. In stratified analysis by polymorphisms, the rs605059 genotype of HSD17B1 significantly modified associations of E2 with intake of n-3 HUFA and fish; the associations were limited to those with the CC genotype. Macronutrient intakes were associated with serum E2 level, and these associations may be modified by HSD17B1 polymorphism in postmenopausal women.", "classifications": [ { "id": "Tanaka", "label": "Group Tanaka", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Sahoko", "last_name": "Takagi", "name": null }, { "creator_type": "author", "first_name": "Mariko", "last_name": "Naito", "name": null }, { "creator_type": "author", "first_name": "Sayo", "last_name": "Kawai", "name": null }, { "creator_type": "author", "first_name": "Rieko", "last_name": "Okada", "name": null }, { "creator_type": "author", "first_name": "Chisato", "last_name": "Nagata", "name": null }, { "creator_type": "author", "first_name": "Satoyo", "last_name": "Hosono", "name": null }, { "creator_type": "author", "first_name": "Yuichiro", "last_name": "Nishida", "name": null }, { "creator_type": "author", "first_name": "Naoyuki", "last_name": "Takashima", "name": null }, { "creator_type": "author", "first_name": "Sadao", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Ippei", "last_name": "Shimoshikiryo", "name": null }, { "creator_type": "author", "first_name": "Haruo", "last_name": "Mikami", "name": null }, { "creator_type": "author", "first_name": "Hirokazu", "last_name": "Uemura", "name": null }, { "creator_type": "author", "first_name": "Nagato", "last_name": "Kuriyama", "name": null }, { "creator_type": "author", "first_name": "Keizo", "last_name": "Ohnaka", "name": null }, { "creator_type": "author", "first_name": "Michiaki", "last_name": "Kubo", "name": null }, { "creator_type": "author", "first_name": "Nobuyuki", "last_name": "Hamajima", "name": null }, { "creator_type": "author", "first_name": "Hideo", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Wakai", "name": null } ], "identifiers": { "doi": { "normalized": "10.1017/s0007114517002239" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "28980890" } }, "mesh": [ { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Aromatase", "descriptor_ui": "D001141", "major_topic": false }, { "descriptor": "Asian People", "descriptor_ui": "D044466", "major_topic": false }, { "descriptor": "Cross-Sectional Studies", "descriptor_ui": "D003430", "major_topic": false }, { "descriptor": "Diet", "descriptor_ui": "D004032", "major_topic": true }, { "descriptor": "Dietary Carbohydrates", "descriptor_ui": "D004040", "major_topic": false }, { "descriptor": "Dietary Fats", "descriptor_ui": "D004041", "major_topic": false }, { "descriptor": "Dietary Proteins", "descriptor_ui": "D004044", "major_topic": false }, { "descriptor": "Estradiol", "descriptor_ui": "D004958", "major_topic": false }, { "descriptor": "Estradiol Dehydrogenases", "descriptor_ui": "D004960", "major_topic": false }, { "descriptor": "Estrogens", "descriptor_ui": "D004967", "major_topic": false }, { "descriptor": "Fatty Acids", "descriptor_ui": "D005227", "major_topic": false }, { "descriptor": "Fatty Acids, Omega-3", "descriptor_ui": "D015525", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Fishes", "descriptor_ui": "D005399", "major_topic": false }, { "descriptor": "Genotyping Techniques", "descriptor_ui": "D060005", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Japan", "descriptor_ui": "D007564", "major_topic": false }, { "descriptor": "Life Style", "descriptor_ui": "D008019", "major_topic": false }, { "descriptor": "Linear Models", "descriptor_ui": "D016014", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Polymorphism, Single Nucleotide", "descriptor_ui": "D020641", "major_topic": true }, { "descriptor": "Postmenopause", "descriptor_ui": "D017698", "major_topic": false }, { "descriptor": "Seafood", "descriptor_ui": "D017747", "major_topic": false }, { "descriptor": "Surveys and Questionnaires", "descriptor_ui": "D011795", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Sep", "date_precision": "unknown", "issue": "6", "normalized_date": null, "pages": "463-472", "proceedings_title": null, "publisher": "", "title": "The British journal of nutrition", "volume": "118", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Macronutrient intakes and serum oestrogen, and interaction with polymorphisms in CYP19A1 and HSD17B1 genes: a cross-sectional study in postmenopausal Japanese women.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Gut microbiota is involved in the metabolism of uremic solutes. However, the precise influence of microbiota to the retention of uremic solutes in CKD is obscure. To clarify this, we compared adenine-induced renal failure and control mice under germ-free or specific pathogen-free (SPF) conditions, examining the metabolite profiles of plasma, feces, and urine using a capillary electrophoresis time-of-flight mass spectrometry-based approach. Mice with renal failure under germ-free conditions demonstrated significant changes in plasma metabolites. Among 183 detected solutes, plasma levels of 11 solutes, including major uremic toxins, were significantly lower in germ-free mice than in SPF mice with renal failure. These 11 solutes were considered microbiota-derived uremic solutes and included indoxyl sulfate, p-cresyl sulfate, phenyl sulfate, cholate, hippurate, dimethylglycine, gamma-guanidinobutyrate, glutarate, 2-hydroxypentanoate, trimethylamine N-oxide, and phenaceturate. Metabolome profiling showed that these solutes were classified into three groups depending on their origins: completely derived from microbiota (indoxyl sulfate, p-cresyl sulfate), derived from both host and microbiota (dimethylglycine), and derived from both microbiota and dietary components (trimethylamine N-oxide). Additionally, germ-free renal failure conditions resulted in the disappearance of colonic short-chain fatty acids, decreased utilization of intestinal amino acids, and more severe renal damage compared with SPF mice with renal failure. Microbiota-derived short-chain fatty acids and efficient amino acid utilization may have a renoprotective effect, and loss of these factors may exacerbate renal damage in germ-free mice with renal failure. Thus, microbiota contributes substantially to the production of harmful uremic solutes, but conversely, growth without microbiota has harmful effects on CKD progression.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Eikan", "last_name": "Mishima", "name": null }, { "creator_type": "author", "first_name": "Shinji", "last_name": "Fukuda", "name": null }, { "creator_type": "author", "first_name": "Chikahisa", "last_name": "Mukawa", "name": null }, { "creator_type": "author", "first_name": "Akinori", "last_name": "Yuri", "name": null }, { "creator_type": "author", "first_name": "Yoshitomi", "last_name": "Kanemitsu", "name": null }, { "creator_type": "author", "first_name": "Yotaro", "last_name": "Matsumoto", "name": null }, { "creator_type": "author", "first_name": "Yasutoshi", "last_name": "Akiyama", "name": null }, { "creator_type": "author", "first_name": "Noriko N.", "last_name": "Fukuda", "name": null }, { "creator_type": "author", "first_name": "Hiroki", "last_name": "Tsukamoto", "name": null }, { "creator_type": "author", "first_name": "Kei", "last_name": "Asaji", "name": null }, { "creator_type": "author", "first_name": "Hisato", "last_name": "Shima", "name": null }, { "creator_type": "author", "first_name": "Koichi", "last_name": "Kikuchi", "name": null }, { "creator_type": "author", "first_name": "Chitose", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Takehiro", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Yoshihisa", "last_name": "Tomioka", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Sadayoshi", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Takaaki", "last_name": "Abe", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.kint.2017.02.011" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "28396122" } }, "mesh": [ { "descriptor": "Acute Kidney Injury", "descriptor_ui": "D058186", "major_topic": false }, { "descriptor": "Adenine", "descriptor_ui": "D000225", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Disease Models, Animal", "descriptor_ui": "D004195", "major_topic": false }, { "descriptor": "Disease Progression", "descriptor_ui": "D018450", "major_topic": false }, { "descriptor": "Electrophoresis, Capillary", "descriptor_ui": "D019075", "major_topic": false }, { "descriptor": "Fatty Acids, Volatile", "descriptor_ui": "D005232", "major_topic": false }, { "descriptor": "Gastrointestinal Microbiome", "descriptor_ui": "D000069196", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Kidney", "descriptor_ui": "D007668", "major_topic": false }, { "descriptor": "Mass Spectrometry", "descriptor_ui": "D013058", "major_topic": false }, { "descriptor": "Metabolome", "descriptor_ui": "D055442", "major_topic": true }, { "descriptor": "Metabolomics", "descriptor_ui": "D055432", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Renal Insufficiency, Chronic", "descriptor_ui": "D051436", "major_topic": false }, { "descriptor": "Specific Pathogen-Free Organisms", "descriptor_ui": "D013047", "major_topic": false }, { "descriptor": "Toxins, Biological", "descriptor_ui": "D014118", "major_topic": false }, { "descriptor": "Uremia", "descriptor_ui": "D014511", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Sep", "date_precision": "unknown", "issue": "3", "normalized_date": null, "pages": "634-645", "proceedings_title": null, "publisher": "", "title": "Kidney international", "volume": "92", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Evaluation of the impact of gut microbiota on uremic solute accumulation by a CE-TOFMS-based metabolomics approach.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "In this paper, a free boundary problem for cell protrusion formation is studied theoretically and numerically. The cell membrane is precisely described thanks to a level set function, whose motion is due to specific signalling pathways. The aim is to model the chemical interactions between the cell and its environment, in the process of invadopodia or pseudopodia formation. The model consists of Laplace equation with Dirichlet condition inside the cell coupled to Laplace equation with Neumann condition in the outer domain. The actin polymerization is accounted for as the gradient of the inner signal, which drives the motion of the interface. We prove the well-posedness of our free boundary problem under a sign condition on the datum. This criterion ensures the consistency of the model, and provides conditions to focus on for any enrichment of the model. We then propose a new first order Cartesian finite-difference method to solve the problem. We eventually exhibit the main biological features that can be accounted for by the model: the formation of thin and elongated protrusions as for invadopodia, or larger protrusion as for pseudopodia, depending on the source term in the equation. The model provides the theoretical and numerical grounds for single cell migration modeling, whose formulation is valid in 2D and 3D. In particular, specific chemical reactions that occurred at the cell membrane could be precisely described in forthcoming works.", "classifications": [ { "id": "Suzuki", "label": "Group Suzuki", "parent": "Takekawa", "type": "group" }, { "id": "Takekawa", "label": "Team Takekawa", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Olivier", "last_name": "Gallinato", "name": null }, { "creator_type": "author", "first_name": "Masahito", "last_name": "Ohta", "name": null }, { "creator_type": "author", "first_name": "Clair", "last_name": "Poignard", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Suzuki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/s00285-016-1080-7" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "27921151" } }, "mesh": [ { "descriptor": "Cell Membrane", "descriptor_ui": "D002462", "major_topic": false }, { "descriptor": "Cell Movement", "descriptor_ui": "D002465", "major_topic": false }, { "descriptor": "Environment", "descriptor_ui": "D004777", "major_topic": false }, { "descriptor": "Models, Biological", "descriptor_ui": "D008954", "major_topic": true }, { "descriptor": "Pseudopodia", "descriptor_ui": "D011554", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Aug", "date_precision": "unknown", "issue": "2", "normalized_date": null, "pages": "263-307", "proceedings_title": null, "publisher": "", "title": "Journal of mathematical biology", "volume": "75", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Free boundary problem for cell protrusion formations: theoretical and numerical aspects.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Replicative aging has been demonstrated in asymmetrically dividing unicellular organisms, seemingly caused by unequal damage partitioning. Although asymmetric segregation and inheritance of potential aging factors also occur in symmetrically dividing species, it nevertheless remains controversial whether this results in aging. Based on large-scale single-cell lineage data obtained by time-lapse microscopy with a microfluidic device, in this report, we demonstrate the absence of replicative aging in old-pole cell lineages of Schizosaccharomyces pombe cultured under constant favorable conditions. By monitoring more than 1,500 cell lineages in 7 different culture conditions, we showed that both cell division and death rates are remarkably constant for at least 50-80 generations. Our measurements revealed that the death rate per cellular generation increases with the division rate, pointing to a physiological trade-off with fast growth under balanced growth conditions. We also observed the formation and inheritance of Hsp104-associated protein aggregates, which are a potential aging factor in old-pole cell lineages, and found that these aggregates exhibited a tendency to preferentially remain at the old poles for several generations. However, the aggregates were eventually segregated from old-pole cells upon cell division and probabilistically allocated to new-pole cells. We found that cell deaths were typically preceded by sudden acceleration of protein aggregation; thus, a relatively large amount of protein aggregates existed at the very ends of the dead cell lineages. Our lineage tracking analyses, however, revealed that the quantity and inheritance of protein aggregates increased neither cellular generation time nor cell death initiation rates. Furthermore, our results demonstrated that unusually large amounts of protein aggregates induced by oxidative stress exposure did not result in aging; old-pole cells resumed normal growth upon stress removal, despite the fact that most of them inherited significant quantities of aggregates. These results collectively indicate that protein aggregates are not a major determinant of triggering cell death in S. pombe and thus cannot be an appropriate molecular marker or index for replicative aging under both favorable and stressful environmental conditions.", "classifications": [ { "id": "Wakamoto", "label": "Group Wakamoto", "parent": "Wakamoto", "type": "group" }, { "id": "Wakamoto", "label": "Team Wakamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Hidenori", "last_name": "Nakaoka", "name": null }, { "creator_type": "author", "first_name": "Yuichi", "last_name": "Wakamoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1371/journal.pbio.2001109" }, "pmcid": { "normalized": "PMC5478097" }, "pmid": { "normalized": "28632741" } }, "mesh": [ { "descriptor": "Adenosine Triphosphatases", "descriptor_ui": "D000251", "major_topic": false }, { "descriptor": "Asymmetric Cell Division", "descriptor_ui": "D060049", "major_topic": true }, { "descriptor": "Biomarkers", "descriptor_ui": "D015415", "major_topic": false }, { "descriptor": "Cell Tracking", "descriptor_ui": "D058948", "major_topic": false }, { "descriptor": "DNA Replication", "descriptor_ui": "D004261", "major_topic": false }, { "descriptor": "Gene Deletion", "descriptor_ui": "D017353", "major_topic": false }, { "descriptor": "Heat-Shock Proteins", "descriptor_ui": "D006360", "major_topic": false }, { "descriptor": "Luminescent Proteins", "descriptor_ui": "D008164", "major_topic": false }, { "descriptor": "Microbial Viability", "descriptor_ui": "D050296", "major_topic": false }, { "descriptor": "Microfluidics", "descriptor_ui": "D044085", "major_topic": false }, { "descriptor": "Microscopy, Confocal", "descriptor_ui": "D018613", "major_topic": false }, { "descriptor": "Microscopy, Fluorescence", "descriptor_ui": "D008856", "major_topic": false }, { "descriptor": "Orthoreovirus", "descriptor_ui": "D018165", "major_topic": false }, { "descriptor": "Oxidative Stress", "descriptor_ui": "D018384", "major_topic": false }, { "descriptor": "Peptide Fragments", "descriptor_ui": "D010446", "major_topic": false }, { "descriptor": "Protein Aggregates", "descriptor_ui": "D066329", "major_topic": true }, { "descriptor": "Recombinant Fusion Proteins", "descriptor_ui": "D011993", "major_topic": false }, { "descriptor": "Schizosaccharomyces", "descriptor_ui": "D012568", "major_topic": false }, { "descriptor": "Schizosaccharomyces pombe Proteins", "descriptor_ui": "D029702", "major_topic": false }, { "descriptor": "Single-Cell Analysis", "descriptor_ui": "D059010", "major_topic": false }, { "descriptor": "Spindle Poles", "descriptor_ui": "D064047", "major_topic": false }, { "descriptor": "Stress, Physiological", "descriptor_ui": "D013312", "major_topic": true }, { "descriptor": "Time-Lapse Imaging", "descriptor_ui": "D059008", "major_topic": false }, { "descriptor": "Viral Nonstructural Proteins", "descriptor_ui": "D017361", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Jun", "date_precision": "unknown", "issue": "6", "normalized_date": null, "pages": "e2001109", "proceedings_title": null, "publisher": "", "title": "PLoS biology", "volume": "15", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Aging, mortality, and the fast growth trade-off of Schizosaccharomyces pombe.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Respiratory activities are produced by medullary respiratory rhythm generators and are modulated from various sites in the lower brainstem, and which are then output as motor activities through premotor efferent networks in the brainstem and spinal cord. Over the past few decades, new knowledge has been accumulated on the anatomical and physiological mechanisms underlying the generation and regulation of respiratory rhythm. In this review, we focus on the recent findings and attempt to elucidate the anatomical and functional mechanisms underlying respiratory control in the lower brainstem and spinal cord.", "classifications": [ { "id": "Yokota", "label": "Group Yokota", "parent": "Enomoto", "type": "group" }, { "id": "Enomoto", "label": "Team Enomoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Keiko", "last_name": "Ikeda", "name": null }, { "creator_type": "author", "first_name": "Kiyoshi", "last_name": "Kawakami", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Onimaru", "name": null }, { "creator_type": "author", "first_name": "Yasumasa", "last_name": "Okada", "name": null }, { "creator_type": "author", "first_name": "Shigefumi", "last_name": "Yokota", "name": null }, { "creator_type": "author", "first_name": "Naohiro", "last_name": "Koshiya", "name": null }, { "creator_type": "author", "first_name": "Yoshitaka", "last_name": "Oku", "name": null }, { "creator_type": "author", "first_name": "Makito", "last_name": "Iizuka", "name": null }, { "creator_type": "author", "first_name": "Hidehiko", "last_name": "Koizumi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/s12576-016-0475-y" }, "pmcid": { "normalized": "PMC5368202" }, "pmid": { "normalized": "27535569" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Brain Stem", "descriptor_ui": "D001933", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Medulla Oblongata", "descriptor_ui": "D008526", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Respiration", "descriptor_ui": "D012119", "major_topic": true }, { "descriptor": "Respiratory Center", "descriptor_ui": "D012125", "major_topic": false }, { "descriptor": "Spinal Cord", "descriptor_ui": "D013116", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Jan", "date_precision": "unknown", "issue": "1", "normalized_date": null, "pages": "45-62", "proceedings_title": null, "publisher": "", "title": "The journal of physiological sciences : JPS", "volume": "67", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "The respiratory control mechanisms in the brainstem and spinal cord: integrative views of the neuroanatomy and neurophysiology.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "We report that population dynamics in fluctuating environments is characterized by a mathematically equivalent structure to steady-state thermodynamics. By employing the structure, population growth in fluctuating environments is decomposed into housekeeping and excess parts. The housekeeping part represents the integral of the stationary growth rate for each condition during a history of the environmental change. The excess part accounts for the excess growth induced by environmental fluctuations. Focusing on the excess growth, we obtain a Clausius inequality, which gives the upper bound of the excess growth. The equality is shown to be achieved in quasistatic environmental changes. We also clarify that this bound can be evaluated by the \"lineage fitness\", which is an experimentally observable quantity.", "classifications": [ { "id": "Kobayashi", "label": "Group Kobayashi", "parent": "Wakamoto", "type": "group" }, { "id": "Wakamoto", "label": "Team Wakamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yuki", "last_name": "Sughiyama", "name": null }, { "creator_type": "author", "first_name": "Tetsuya J.", "last_name": "Kobayashi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1103/physreve.95.012131" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "28208406" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Environment", "descriptor_ui": "D004777", "major_topic": false }, { "descriptor": "Genetic Fitness", "descriptor_ui": "D056084", "major_topic": false }, { "descriptor": "Models, Theoretical", "descriptor_ui": "D008962", "major_topic": true }, { "descriptor": "Population Growth", "descriptor_ui": "D011158", "major_topic": true }, { "descriptor": "Thermodynamics", "descriptor_ui": "D013816", "major_topic": true } ], "publication": { "conference_name": null, "date": "2017 Jan", "date_precision": "unknown", "issue": "1-1", "normalized_date": null, "pages": "012131", "proceedings_title": null, "publisher": "", "title": "Physical review. E", "volume": "95", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Steady-state thermodynamics for population growth in fluctuating environments.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "In gene function analysis, it is arduous to identify gene function individually, and the way to screen out all involved genes according to a particular phenotype or disease usually shows us little information for a specific problem. We present a data-driven analysis system based on wild type (WT) embryos to study the concrete function of each gene associated with certain category of abnormal phenotypes. It can be applied to genes with very few RNAi embryos. Instead of presupposing the particular function of a gene, its function is confirmed by the statistical testing of built models. The scheme includes the following five: first, verify the to be detected genes and determine related recognized features according to the given category; second, compute the value of each feature based on WT embryos and merge them by principal component analysis (PCA); third, for each of the selected components of PCA, build a normal distribution and verify its normality; fourth, project the RNAi embryos to each component and probe them; and finally, analyze the more detailed functions of each gene based on the physical or biological meaning of each component. Choosing the first-round asymmetric division process of Caenorhabditis elegans as the phenotype, experimental results show that on the different aspects of the asymmetric division process, par-2, par-3, and let-754 are related to scalar differences; dcn-1 and mcm-5 are associated with the divergences of scalar variation, which may reflect the disaccord in development; and dcn-1, par-2, and par-3 are involved with morphological discrepancies.", "classifications": [ { "id": "Onami", "label": "Group Onami", "parent": "Fujiwara", "type": "group" }, { "id": "Fujiwara", "label": "Team Fujiwara", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Sihai", "last_name": "Yang", "name": null }, { "creator_type": "author", "first_name": "Xianhua", "last_name": "Han", "name": null }, { "creator_type": "author", "first_name": "Yukako", "last_name": "Tohsato", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Kyoda", "name": null }, { "creator_type": "author", "first_name": "Shuichi", "last_name": "Onami", "name": null }, { "creator_type": "author", "first_name": "Ikuko", "last_name": "Nishikawa", "name": null }, { "creator_type": "author", "first_name": "Yenwei", "last_name": "Chen", "name": null } ], "identifiers": { "doi": { "normalized": "10.1089/cmb.2016.0210" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "28177654" } }, "mesh": [ { "descriptor": "Algorithms", "descriptor_ui": "D000465", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Asymmetric Cell Division", "descriptor_ui": "D060049", "major_topic": false }, { "descriptor": "Caenorhabditis elegans", "descriptor_ui": "D017173", "major_topic": false }, { "descriptor": "Caenorhabditis elegans Proteins", "descriptor_ui": "D029742", "major_topic": false }, { "descriptor": "Computational Biology", "descriptor_ui": "D019295", "major_topic": false }, { "descriptor": "Gene Expression Regulation, Developmental", "descriptor_ui": "D018507", "major_topic": false }, { "descriptor": "Gene Silencing", "descriptor_ui": "D020868", "major_topic": false }, { "descriptor": "Phenotype", "descriptor_ui": "D010641", "major_topic": false }, { "descriptor": "Principal Component Analysis", "descriptor_ui": "D025341", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 May", "date_precision": "unknown", "issue": "5", "normalized_date": null, "pages": "436-446", "proceedings_title": null, "publisher": "", "title": "Journal of computational biology : a journal of computational molecular cell biology", "volume": "24", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Phenotype Analysis Method for Identification of Gene Functions Involved in Asymmetric Division of Caenorhabditis elegans.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: As the prevalence of nonalcoholic fatty liver disease (NAFLD), including steatosis and nonalcoholic steatohepatitis, is increasing, novel dietary approaches are required for the prevention and treatment of NAFLD. OBJECTIVE: We evaluated the potential of mung bean protein isolate (MuPI) to prevent NAFLD progression. METHODS: In Expts. 1 and 2, the hepatic triglyceride (TG) concentration was compared between 8-wk-old male mice fed a high-fat diet (61% of energy from fat) containing casein, MuPI, and soy protein isolate and an MuPI-constituent amino acid mixture as a source of amino acids (18% of energy) for 4 wk. In Expt. 3, hepatic fatty acid synthase (Fasn) expression was evaluated in 8-wk-old male Fasn-promoter-reporter mice fed a casein- or MuPI-containing high-fat diet for 20 wk. In Expt. 4, hepatic fibrosis was examined in 8-wk-old male mice fed an atherogenic diet (61% of energy from fat, containing 1.3 g cholesterol/100 g diet) containing casein or MuPI (18% of energy) as a protein source for 20 wk. RESULTS: In the high fat-diet mice, the hepatic TG concentration in the MuPI group decreased by 66% and 47% in Expt. 1 compared with the casein group (P < 0.001) and the soy protein isolate group (P = 0.001), respectively, and decreased by 56% in Expt. 2 compared with the casein group (P = 0.011). However, there was no difference between the MuPI-constituent amino acid mixture and casein groups in Expt. 2. In Expt. 3, Fasn-promoter-reporter activity and hepatic TG concentration were lower in the MuPI group than in those fed casein (P < 0.05). In Expt. 4, in mice fed an atherogenic diet, hepatic fibrosis was not induced in the MuPI group, whereas it developed overtly in the casein group. CONCLUSION: MuPI potently reduced hepatic lipid accumulation in mice and may be a potential foodstuff to prevent NAFLD onset and progression.", "classifications": [ { "id": "Inaba", "label": "Group Inaba", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Yuka", "last_name": "Inaba", "name": null }, { "creator_type": "author", "first_name": "Kumi", "last_name": "Kimura", "name": null }, { "creator_type": "author", "first_name": "Shun-Ichiro", "last_name": "Asahara", "name": null }, { "creator_type": "author", "first_name": "Yoshiaki", "last_name": "Kido", "name": null }, { "creator_type": "author", "first_name": "Michihiro", "last_name": "Matsumoto", "name": null }, { "creator_type": "author", "first_name": "Takayasu", "last_name": "Motoyama", "name": null }, { "creator_type": "author", "first_name": "Nobuhiko", "last_name": "Tachibana", "name": null }, { "creator_type": "author", "first_name": "Shuichi", "last_name": "Kaneko", "name": null }, { "creator_type": "author", "first_name": "Mitsutaka", "last_name": "Kohno", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Inoue", "name": null } ], "identifiers": { "doi": { "normalized": "10.3945/jn.116.231662" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "27903831" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Dietary Fats", "descriptor_ui": "D004041", "major_topic": false }, { "descriptor": "Dietary Proteins", "descriptor_ui": "D004044", "major_topic": false }, { "descriptor": "Fatty Acid Synthase, Type I", "descriptor_ui": "D054890", "major_topic": false }, { "descriptor": "Fatty Liver", "descriptor_ui": "D005234", "major_topic": false }, { "descriptor": "Gene Expression Regulation", "descriptor_ui": "D005786", "major_topic": false }, { "descriptor": "Inflammation", "descriptor_ui": "D007249", "major_topic": false }, { "descriptor": "Liver Cirrhosis", "descriptor_ui": "D008103", "major_topic": false }, { "descriptor": "Luciferases", "descriptor_ui": "D008156", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Transgenic", "descriptor_ui": "D008822", "major_topic": false }, { "descriptor": "Vigna", "descriptor_ui": "D000070658", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Jan", "date_precision": "unknown", "issue": "1", "normalized_date": null, "pages": "52-60", "proceedings_title": null, "publisher": "", "title": "The Journal of nutrition", "volume": "147", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Dietary Mung Bean Protein Reduces Hepatic Steatosis, Fibrosis, and Inflammation in Male Mice with Diet-Induced, Nonalcoholic Fatty Liver Disease.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Epithelial invagination is one of the fundamental deformation modes during morphogenesis, and is essential for deriving the three-dimensional shapes of organs from a flat epithelial sheet. Invagination occurs in an orderly manner according to the spatial pattern of the contractile cells; however, it remains elusive how tissue deformation can be caused by cellular activity in the patterned region. In this study, we investigated the mechanical role of the spatial patterns of the contractile cells in invagination of growing tissue using multicellular dynamics simulations. We found that cell proliferation and apical constriction were responsible for expanding the degree of tissue deformation and determining the location of the deformation, respectively. The direction of invagination depended on the spatial pattern of the contractile cells. Further, comparing the simulation results of surface and line contractions as possible modes of apical constriction, we found that the direction of invagination differed between these two modes even if the spatial pattern was the same. These results indicate that the buckling of the epithelial cell sheet caused by cell proliferation causes the invagination, with the direction and location determined by the configuration of the wedge-shaped cells given by the spatial pattern of the contractile cells.", "classifications": [ { "id": "Okuda", "label": "Group Okuda", "parent": "Imayoshi", "type": "group" }, { "id": "Imayoshi", "label": "Team Imayoshi", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yasuhiro", "last_name": "Inoue", "name": null }, { "creator_type": "author", "first_name": "Tadashi", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Satoru", "last_name": "Okuda", "name": null }, { "creator_type": "author", "first_name": "Taiji", "last_name": "Adachi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/dgd.12374" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "28707336" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Proliferation", "descriptor_ui": "D049109", "major_topic": true }, { "descriptor": "Epithelium", "descriptor_ui": "D004848", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Models, Biological", "descriptor_ui": "D008954", "major_topic": true }, { "descriptor": "Morphogenesis", "descriptor_ui": "D009024", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Jun", "date_precision": "unknown", "issue": "5", "normalized_date": null, "pages": "444-454", "proceedings_title": null, "publisher": "", "title": "Development, growth & differentiation", "volume": "59", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Mechanical role of the spatial patterns of contractile cells in invagination of growing epithelial tissue.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Transient receptor potential (TRP) channels constitute a large family of versatile multi-signal transducers. In particular, TRP canonical (TRPC) channels are known as receptor-operated, non-selective cation channels. TRPC3 and TRPC6, two members in the TRPC family, are highly expressed in the heart, and participate in the pathogenesis of cardiac hypertrophy and heart failure as a pathological response to chronic mechanical stress. In the pathological response, myocardial stretch increases intracellular Ca(2+) levels and activates nuclear factor of activated T cells to induce cardiac hypertrophy. Recent studies have revealed that TRPC3 and TRPC6 also contribute to the physiological stretch-induced slow force response (SFR), a slow increase in the Ca(2+) transient and twitch force during stretch. In the physiological response, a stretch-induced increase in intracellular Ca(2+) mediated by TRPC3 and TRPC6 causes the SFR. We here overview experimental evidence of the involvement of TRPC3 and TRPC6 in cardiac physiology and pathophysiology in response to stretch.", "classifications": [ { "id": "Nishida", "label": "Group Nishida", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yohei", "last_name": "Yamaguchi", "name": null }, { "creator_type": "author", "first_name": "Gentaro", "last_name": "Iribe", "name": null }, { "creator_type": "author", "first_name": "Motohiro", "last_name": "Nishida", "name": null }, { "creator_type": "author", "first_name": "Keiji", "last_name": "Naruse", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.pbiomolbio.2017.06.010" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "28645743" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Heart", "descriptor_ui": "D006321", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Myocardium", "descriptor_ui": "D009206", "major_topic": false }, { "descriptor": "TRPC Cation Channels", "descriptor_ui": "D050052", "major_topic": false }, { "descriptor": "TRPC6 Cation Channel", "descriptor_ui": "D000074287", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Nov", "date_precision": "unknown", "issue": "Pt B", "normalized_date": null, "pages": "264-272", "proceedings_title": null, "publisher": "", "title": "Progress in biophysics and molecular biology", "volume": "130", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Role of TRPC3 and TRPC6 channels in the myocardial response to stretch: Linking physiology and pathophysiology.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "It has been proposed that the CLOCK-ARNTL (BMAL1) complex drives circadian transcription of thousands of genes, including Per and Cry family genes that encode suppressors of CLOCK-ARNTL-dependent transcription. However, recent studies demonstrated that 70-80% of circadian-oscillating mRNAs have no obvious rhythms in their de novo transcription, indicating the potential importance of post-transcriptional regulation. Our CLOCK-ChIP-seq analysis identified rhythmic expression of adenosine deaminase, RNA-specific, B1 (Adarb1, also known as Adar2), an adenosine-to-inosine (A-to-I) RNA-editing enzyme. RNA-seq showed circadian rhythms of ADARB1-mediated A-to-I editing in a variety of transcripts. In Adarb1-knockout mice, rhythms of large populations of mRNA were attenuated, indicating a profound impact of ADARB1-mediated A-to-I editing on RNA rhythms. Furthermore, Adarb1-knockout mice exhibited short-period rhythms in locomotor activity and gene expression. These phenotypes were associated with abnormal accumulation of CRY2. The present study identifies A-to-I RNA editing as a key mechanism of post-transcriptional regulation in the circadian clockwork.", "classifications": [ { "id": "Kuroda", "label": "Group Kuroda", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Hideki", "last_name": "Terajima", "name": null }, { "creator_type": "author", "first_name": "Hikari", "last_name": "Yoshitane", "name": null }, { "creator_type": "author", "first_name": "Haruka", "last_name": "Ozaki", "name": null }, { "creator_type": "author", "first_name": "Yutaka", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Shigeki", "last_name": "Shimba", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Kuroda", "name": null }, { "creator_type": "author", "first_name": "Wataru", "last_name": "Iwasaki", "name": null }, { "creator_type": "author", "first_name": "Yoshitaka", "last_name": "Fukada", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/ng.3731" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "27893733" } }, "mesh": [ { "descriptor": "Adenosine", "descriptor_ui": "D000241", "major_topic": false }, { "descriptor": "Adenosine Deaminase", "descriptor_ui": "D000243", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Aryl Hydrocarbon Receptor Nuclear Translocator", "descriptor_ui": "D051784", "major_topic": false }, { "descriptor": "Circadian Rhythm", "descriptor_ui": "D002940", "major_topic": false }, { "descriptor": "Cryptochromes", "descriptor_ui": "D056931", "major_topic": false }, { "descriptor": "Gene Expression Regulation", "descriptor_ui": "D005786", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Inosine", "descriptor_ui": "D007288", "major_topic": false }, { "descriptor": "Liver", "descriptor_ui": "D008099", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "RNA", "descriptor_ui": "D012313", "major_topic": false }, { "descriptor": "RNA-Binding Proteins", "descriptor_ui": "D016601", "major_topic": false }, { "descriptor": "Transcription, Genetic", "descriptor_ui": "D014158", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Jan", "date_precision": "unknown", "issue": "1", "normalized_date": null, "pages": "146-151", "proceedings_title": null, "publisher": "", "title": "Nature genetics", "volume": "49", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "ADARB1 catalyzes circadian A-to-I editing and regulates RNA rhythm.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Long-chain acyl-coenzyme A (CoA) synthetase 3 (ACSL3) is an androgen-responsive gene involved in the generation of fatty acyl-CoA esters. ACSL3 is expressed in both androgen-sensitive and castration-resistant prostate cancer (CRPC). However, its role in prostate cancer remains elusive. We overexpressed ACSL3 in androgen-dependent LNCaP cells and examined the downstream effectors of ACSL3. Furthermore, we examined the role of ACSL3 in the androgen metabolism of prostate cancer. ACSL3 overexpression led to upregulation of several genes such as aldo-keto reductase 1C3 (AKR1C3) involved in steroidogenesis, which utilizes adrenal androgen dehydroepiandrosterone sulfate (DHEAS) as substrate, and downregulated androgen-inactivating enzyme UDP-glucuronosyltransferase 2 (UGT2B). Exposure to DHEAS significantly increased testosterone levels and cell proliferative response in ACSL3-overexpressing cells when compared to that in control cells. A public database showed that ACSL3 level was higher in CRPC than in hormone-sensitive prostate cancer. CRPC cells showed an increased expression of ACSL3 and an expression pattern of AKR1C3 and UGT2B similar to ACSL3-overexpressing cells. DHEAS stimulation significantly promoted the proliferation of CRPC cells when compared to that of LNCaP cells. These findings suggest that ACSL3 contributes to the growth of CRPC through intratumoral steroidogenesis (i.e. promoting androgen synthesis from DHEAS and preventing the catabolism of active androgens).", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Toshiro", "last_name": "Migita", "name": null }, { "creator_type": "author", "first_name": "Ken-Ichi", "last_name": "Takayama", "name": null }, { "creator_type": "author", "first_name": "Tomohiko", "last_name": "Urano", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Obinata", "name": null }, { "creator_type": "author", "first_name": "Kazutaka", "last_name": "Ikeda", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Satoru", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Inoue", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/cas.13339" }, "pmcid": { "normalized": "PMC5623750" }, "pmid": { "normalized": "28771887" } }, "mesh": [ { "descriptor": "3-Hydroxysteroid Dehydrogenases", "descriptor_ui": "D015096", "major_topic": false }, { "descriptor": "Aldo-Keto Reductase Family 1 Member C3", "descriptor_ui": "D000074425", "major_topic": false }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Cell Proliferation", "descriptor_ui": "D049109", "major_topic": false }, { "descriptor": "Coenzyme A Ligases", "descriptor_ui": "D003066", "major_topic": false }, { "descriptor": "Dehydroepiandrosterone Sulfate", "descriptor_ui": "D019314", "major_topic": false }, { "descriptor": "Gene Expression Regulation, Neoplastic", "descriptor_ui": "D015972", "major_topic": false }, { "descriptor": "Glucuronosyltransferase", "descriptor_ui": "D014453", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Hydroxyprostaglandin Dehydrogenases", "descriptor_ui": "D006911", "major_topic": false }, { "descriptor": "Lipogenesis", "descriptor_ui": "D050155", "major_topic": false }, { "descriptor": "Long-Chain-Fatty-Acid-CoA Ligase", "descriptor_ui": "D000098859", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Prostatic Neoplasms, Castration-Resistant", "descriptor_ui": "D064129", "major_topic": false }, { "descriptor": "Testosterone", "descriptor_ui": "D013739", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Oct", "date_precision": "unknown", "issue": "10", "normalized_date": null, "pages": "2011-2021", "proceedings_title": null, "publisher": "", "title": "Cancer science", "volume": "108", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "ACSL3 promotes intratumoral steroidogenesis in prostate cancer cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "To understand organ morphogenetic mechanisms, it is essential to clarify how spatiotemporally-regulated molecular/cellular dynamics causes physical tissue deformation. In the case of vertebrate limb development, while some of the genes and oriented cell behaviors underlying morphogenesis have been revealed, tissue deformation dynamics remains incompletely understood. We here introduce our recent work on the reconstruction of tissue deformation dynamics in chick limb development from cell lineage tracing data. This analysis has revealed globally-aligned anisotropic tissue deformation along the proximo-distal axis not only in the distal region but also in the whole limb bud. This result points to a need, as a future challenge, to find oriented molecular/cellular behaviors for realizing the observed anisotropic tissue deformation in both proximal and distal regions, which will lead to systems understanding of limb morphogenesis.", "classifications": [ { "id": "Morishita", "label": "Group Morishita", "parent": "Morishita", "type": "group" }, { "id": "Morishita", "label": "Team Morishita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Takayuki", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Yoshihiro", "last_name": "Morishita", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.gde.2017.04.005" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "28502890" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Anisotropy", "descriptor_ui": "D016880", "major_topic": false }, { "descriptor": "Cell Lineage", "descriptor_ui": "D019070", "major_topic": false }, { "descriptor": "Chick Embryo", "descriptor_ui": "D002642", "major_topic": false }, { "descriptor": "Limb Buds", "descriptor_ui": "D018878", "major_topic": false }, { "descriptor": "Organogenesis", "descriptor_ui": "D038081", "major_topic": false }, { "descriptor": "Vertebrates", "descriptor_ui": "D014714", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Aug", "date_precision": "unknown", "issue": "", "normalized_date": null, "pages": "108-114", "proceedings_title": null, "publisher": "", "title": "Current opinion in genetics & development", "volume": "45", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "A quantitative approach to understanding vertebrate limb morphogenesis at the macroscopic tissue level.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Maintaining a redox balance by means of precisely controlled systems that regulate production, and elimination, and metabolism of electrophilic substances (electrophiles) is essential for normal cardiovascular function. Electrophilic signaling is mainly regulated by endogenous electrophiles that are generated from reactive oxygen species, nitric oxide, and the derivative reactive species of nitric oxide during stress responses, as well as by exogenous electrophiles including compounds in foods and environmental pollutants. Among electrophiles formed endogenously, 8-nitroguanosine 3',5'-cyclic monophosphate (8-nitro-cGMP) has unique cell signaling functions, and pathways for its biosynthesis, signaling mechanism, and metabolism in cells have been clarified. Reactive persulfide species such as cysteine persulfides and polysulfides that are endogenously produced in cells are likely to be involved in 8-nitro-cGMP metabolism. These new aspects of redox biology may stimulate innovative and multidisciplinary research in cardiovascular physiology and pathophysiology. In our review, we focus on the redox-dependent regulation of electrophilic signaling via reduction and metabolism of electrophiles by reactive persulfides in cardiac cells, and we include suggestions for a new therapeutic strategy for cardiovascular disease.", "classifications": [ { "id": "Akaike", "label": "Group Akaike", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Group Nishida", "parent": "Nishida", "type": "group" }, { "id": "Nishimura", "label": "Group Nishimura", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Motohiro", "last_name": "Nishida", "name": null }, { "creator_type": "author", "first_name": "Akiyuki", "last_name": "Nishimura", "name": null }, { "creator_type": "author", "first_name": "Tetsuro", "last_name": "Matsunaga", "name": null }, { "creator_type": "author", "first_name": "Hozumi", "last_name": "Motohashi", "name": null }, { "creator_type": "author", "first_name": "Shingo", "last_name": "Kasamatsu", "name": null }, { "creator_type": "author", "first_name": "Takaaki", "last_name": "Akaike", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.freeradbiomed.2017.01.024" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "28109891" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cardiomyopathies", "descriptor_ui": "D009202", "major_topic": false }, { "descriptor": "Cyclic GMP", "descriptor_ui": "D006152", "major_topic": false }, { "descriptor": "Cysteine", "descriptor_ui": "D003545", "major_topic": false }, { "descriptor": "Disulfides", "descriptor_ui": "D004220", "major_topic": false }, { "descriptor": "Gene Expression Regulation", "descriptor_ui": "D005786", "major_topic": false }, { "descriptor": "GTP-Binding Proteins", "descriptor_ui": "D019204", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Myocardium", "descriptor_ui": "D009206", "major_topic": false }, { "descriptor": "Myocytes, Cardiac", "descriptor_ui": "D032383", "major_topic": false }, { "descriptor": "Nitric Oxide", "descriptor_ui": "D009569", "major_topic": false }, { "descriptor": "Oxidation-Reduction", "descriptor_ui": "D010084", "major_topic": false }, { "descriptor": "Oxidative Stress", "descriptor_ui": "D018384", "major_topic": false }, { "descriptor": "Protein Aggregation, Pathological", "descriptor_ui": "D066263", "major_topic": false }, { "descriptor": "Reactive Oxygen Species", "descriptor_ui": "D017382", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Sulfides", "descriptor_ui": "D013440", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Aug", "date_precision": "unknown", "issue": "", "normalized_date": null, "pages": "132-140", "proceedings_title": null, "publisher": "", "title": "Free radical biology & medicine", "volume": "109", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Redox regulation of electrophilic signaling by reactive persulfides in cardiac cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The network structure of cellulose fibrils provides mechanical properties to the primary cell wall, thereby determining the shapes and growth patterns of plant cells. Despite intensive studies, the construction process of the network structure in muro remains largely unknown, mainly due to the lack of a robust, straightforward technique to evaluate network configuration. Here, we developed a quantitative confocal imaging method for general use in the study of cell wall dynamics in protoplasts derived from Arabidopsis leaf mesophyll cells. Confocal imaging of regenerating cell walls in protoplasts stained with Calcofluor allowed us to visualize the cellulose network, comprising strings of bundled cellulosic fibrils. Using image analysis techniques, we measured several metrics including total length, which is a measure of the spread of the cellulose network. The total length increased during cell wall regeneration. In a proof-of-concept experiment using microtubule-modifying agents, oryzalin, an inhibitor of microtubule polymerization, inhibited the increase in total length and caused abnormal orientation of the network, as shown by the decrease in the average angle of the cellulose with respect to the cell long axis. Taxol, a microtubule stabilizer, stimulated the bundling of cellulose fibrils, as shown by the increase in skewness in the fluorescence intensity distribution of Calcofluor, and inhibited the increase in total length. These results demonstrate the validity of this method for quantitative imaging of the cellulose network, providing an opportunity to gain insight into the dynamic aspects of cell wall regeneration.", "classifications": [ { "id": "Higaki", "label": "Group Higaki", "parent": "Ueda", "type": "group" }, { "id": "Ueda", "label": "Team Ueda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Hiroaki", "last_name": "Kuki", "name": null }, { "creator_type": "author", "first_name": "Takumi", "last_name": "Higaki", "name": null }, { "creator_type": "author", "first_name": "Ryusuke", "last_name": "Yokoyama", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Kuroha", "name": null }, { "creator_type": "author", "first_name": "Naoki", "last_name": "Shinohara", "name": null }, { "creator_type": "author", "first_name": "Seiichiro", "last_name": "Hasezawa", "name": null }, { "creator_type": "author", "first_name": "Kazuhiko", "last_name": "Nishitani", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/pld3.21" }, "pmcid": { "normalized": "PMC6508514" }, "pmid": { "normalized": "31245675" } }, "mesh": [], "publication": { "conference_name": null, "date": "2017 Dec", "date_precision": "unknown", "issue": "6", "normalized_date": null, "pages": "e00021", "proceedings_title": null, "publisher": "", "title": "Plant direct", "volume": "1", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Quantitative confocal imaging method for analyzing cellulose dynamics during cell wall regeneration in Arabidopsis mesophyll protoplasts.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Background: Although open-ended dietary assessment methods, such as weighed food records (WFRs), are generally considered to be comparable, differences between procedures may influence outcome when WFRs are conducted independently. In this paper, we assess the procedures of WFRs in two studies to describe their dietary assessment procedures and compare the subsequent outcomes. Methods: WFRs of 12 days (3 days for four seasons) were conducted as reference methods for intake data, in accordance with the study protocol, among a subsample of participants of two large cohort studies. We compared the WFR procedures descriptively. We also compared some dietary intake variables, such as the frequency of foods and dishes and contributing foods, to determine whether there were differences in the portion size distribution and intra- and inter-individual variation in nutrient intakes caused by the difference in procedures. Results: General procedures of the dietary records were conducted in accordance with the National Health and Nutrition Survey and were the same for both studies. Differences were seen in 1) selection of multiple days (non-consecutive days versus consecutive days); and 2) survey sheet recording method (individual versus family participation). However, the foods contributing to intake of energy and selected nutrients, the portion size distribution, and intra- and inter-individual variation in nutrient intakes were similar between the two studies. Conclusion: Our comparison of WFR procedures in two independent studies revealed several differences. Notwithstanding these procedural differences, however, the subsequent outcomes were similar.", "classifications": [ { "id": "Tanaka", "label": "Group Tanaka", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yuri", "last_name": "Ishii", "name": null }, { "creator_type": "author", "first_name": "Junko", "last_name": "Ishihara", "name": null }, { "creator_type": "author", "first_name": "Ribeka", "last_name": "Takachi", "name": null }, { "creator_type": "author", "first_name": "Yurie", "last_name": "Shinozawa", "name": null }, { "creator_type": "author", "first_name": "Nahomi", "last_name": "Imaeda", "name": null }, { "creator_type": "author", "first_name": "Chiho", "last_name": "Goto", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Wakai", "name": null }, { "creator_type": "author", "first_name": "Toshiaki", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Hiroyasu", "last_name": "Iso", "name": null }, { "creator_type": "author", "first_name": "Kazutoshi", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Junta", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Taichi", "last_name": "Shimazu", "name": null }, { "creator_type": "author", "first_name": "Taiki", "last_name": "Yamaji", "name": null }, { "creator_type": "author", "first_name": "Shizuka", "last_name": "Sasazuki", "name": null }, { "creator_type": "author", "first_name": "Norie", "last_name": "Sawada", "name": null }, { "creator_type": "author", "first_name": "Motoki", "last_name": "Iwasaki", "name": null }, { "creator_type": "author", "first_name": "Haruo", "last_name": "Mikami", "name": null }, { "creator_type": "author", "first_name": "Kiyonori", "last_name": "Kuriki", "name": null }, { "creator_type": "author", "first_name": "Mariko", "last_name": "Naito", "name": null }, { "creator_type": "author", "first_name": "Naoko", "last_name": "Okamoto", "name": null }, { "creator_type": "author", "first_name": "Fumi", "last_name": "Kondo", "name": null }, { "creator_type": "author", "first_name": "Satoyo", "last_name": "Hosono", "name": null }, { "creator_type": "author", "first_name": "Naoko", "last_name": "Miyagawa", "name": null }, { "creator_type": "author", "first_name": "Etsuko", "last_name": "Ozaki", "name": null }, { "creator_type": "author", "first_name": "Sakurako", "last_name": "Katsuura-Kamano", "name": null }, { "creator_type": "author", "first_name": "Keizo", "last_name": "Ohnaka", "name": null }, { "creator_type": "author", "first_name": "Hinako", "last_name": "Nanri", "name": null }, { "creator_type": "author", "first_name": "Noriko", "last_name": "Tsunematsu-Nakahata", "name": null }, { "creator_type": "author", "first_name": "Takamasa", "last_name": "Kayama", "name": null }, { "creator_type": "author", "first_name": "Ayako", "last_name": "Kurihara", "name": null }, { "creator_type": "author", "first_name": "Shiomi", "last_name": "Kojima", "name": null }, { "creator_type": "author", "first_name": "Hideo", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Shoichiro", "last_name": "Tsugane", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.je.2016.08.008" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "28302344" } }, "mesh": [ { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Aged, 80 and over", "descriptor_ui": "D000369", "major_topic": false }, { "descriptor": "Cohort Studies", "descriptor_ui": "D015331", "major_topic": false }, { "descriptor": "Diet Records", "descriptor_ui": "D015930", "major_topic": true }, { "descriptor": "Diet Surveys", "descriptor_ui": "D004034", "major_topic": false }, { "descriptor": "Energy Intake", "descriptor_ui": "D002149", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Japan", "descriptor_ui": "D007564", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Reproducibility of Results", "descriptor_ui": "D015203", "major_topic": false }, { "descriptor": "Validation Studies as Topic", "descriptor_ui": "D054928", "major_topic": true } ], "publication": { "conference_name": null, "date": "2017 Jul", "date_precision": "unknown", "issue": "7", "normalized_date": null, "pages": "331-337", "proceedings_title": null, "publisher": "", "title": "Journal of Epidemiology", "volume": "27", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Comparison of weighed food record procedures for the reference methods in two validation studies of food frequency questionnaires.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "There is currently no clinical data regarding the efficacy of trastuzumab treatment for the progression of human epidermal growth factor receptor 2 (HER2)-positive advanced gastric cancer (AGC) occurring during trastuzumab-based chemotherapy. The aim of this study was to retrospectively examine the clinical benefits of trastuzumab for HER2-positive AGC patients who progressed during first-line trastuzumab-based chemotherapy. Among the 108 patients treated with trastuzumab combined with fluoropyrimidine and cisplatin as first-line therapy, 46 HER2-positive AGC patients who received cytotoxic agents with or without trastuzumab subsequent to disease progression were included. Of these, the efficacy and safety outcomes of 26 patients who continued trastuzumab were compared with those of the 20 patients who discontinued trastuzumab. No difference in response rate (18.2 vs. 15.8%, P=1.00) was observed between the two groups. Progression-free survival (PFS) time was numerically longer in the chemotherapy combination with trastuzumab group than in the chemotherapy combination without trastuzumab group (median, 4.0 vs. 2.3 months), with no significance [hazard ratio (HR), 0.63; P=0.14]. In the subset analysis, continuation of trastuzumab significantly improved PFS time in selected subgroups of patients with tumors exhibiting HER2 expression scores of 3+ (HR, 0.41; P=0.04), intestinal-type histology (HR, 0.32; P<0.01), and a first PFS time of >6 months (HR, 0.44; P=0.04). The survival times for the trastuzumab beyond progression (TBP) and non-TBP groups were similar (HR, 1.06; P=0.88), with equivalent overall survival times in the subgroups with immunohistochemistry scores of 3+ (HR, 0.97; P=0.94), intestinal-type histology (HR, 0.53; P=0.19), and a first PFS time of >6 months (HR, 0.62; P=0.31). There were no differences in the incidence rates of toxicity, including cardiac dysfunction, between the two groups. The study results suggest that selected HER2-positive AGC patients may benefit from trastuzumab continuation during first progression, and further prospective studies are warranted.", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yukiya", "last_name": "Narita", "name": null }, { "creator_type": "author", "first_name": "Shigenori", "last_name": "Kadowaki", "name": null }, { "creator_type": "author", "first_name": "Toshiki", "last_name": "Masuishi", "name": null }, { "creator_type": "author", "first_name": "Hiroya", "last_name": "Taniguchi", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Takahari", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Ura", "name": null }, { "creator_type": "author", "first_name": "Masashi", "last_name": "Ando", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Tajika", "name": null }, { "creator_type": "author", "first_name": "Yasumasa", "last_name": "Niwa", "name": null }, { "creator_type": "author", "first_name": "Tetsuya", "last_name": "Eto", "name": null }, { "creator_type": "author", "first_name": "Hiroki", "last_name": "Hara", "name": null }, { "creator_type": "author", "first_name": "Masako", "last_name": "Asayama", "name": null }, { "creator_type": "author", "first_name": "Kensei", "last_name": "Yamaguchi", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null }, { "creator_type": "author", "first_name": "Kei", "last_name": "Muro", "name": null } ], "identifiers": { "doi": { "normalized": "10.3892/ol.2017.6409" }, "pmcid": { "normalized": "PMC5530221" }, "pmid": { "normalized": "28781693" } }, "mesh": [], "publication": { "conference_name": null, "date": "2017 Aug", "date_precision": "unknown", "issue": "2", "normalized_date": null, "pages": "2545-2551", "proceedings_title": null, "publisher": "", "title": "Oncology letters", "volume": "14", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Correlation between human epidermal growth factor receptor 2 expression level and efficacy of trastuzumab beyond progression in metastatic gastric cancer.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "In endochondral ossification, growth of bones occurs at their growth plate cartilage. While it is known that nitric oxide (NO) synthases are required for proliferation of chondrocytes in growth plate cartilage and growth of bones, the precise mechanism by which NO facilitates these process has not been clarified yet. C-type natriuretic peptide (CNP) also positively regulate elongation of bones through expansion of the growth plate cartilage. Both NO and CNP are known to use cGMP as the second messenger. Recently, 8-nitro-cGMP was identified as a signaling molecule produced in the presence of NO in various types of cells. Here, we found that 8-nitro-cGMP is produced in proliferating chondrocytes in the growth plates, which was enhanced by CNP, in bones cultured ex vivo. In addition, 8-nitro-cGMP promoted bone growth with expansion of the proliferating zone as well as increase in the number of proliferating cells in the growth plates. 8-Nitro-cGMP also promoted the proliferation of chondrocytes in vitro. On the other hand, 8-bromo-cGMP enhanced the growth of bones with expansion of hypertrophic zone of the growth plates without affecting either the width of proliferating zone or proliferation of chondrocytes. These results indicate that 8-nitro-cGMP formed in growth plate cartilage accelerates chondrocyte proliferation and bone growth as a downstream molecule of NO.", "classifications": [ { "id": "Akaike", "label": "Group Akaike", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Marie", "last_name": "Hoshino", "name": null }, { "creator_type": "author", "first_name": "Kotaro", "last_name": "Kaneko", "name": null }, { "creator_type": "author", "first_name": "Yoichi", "last_name": "Miyamoto", "name": null }, { "creator_type": "author", "first_name": "Kentaro", "last_name": "Yoshimura", "name": null }, { "creator_type": "author", "first_name": "Dai", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Takaaki", "last_name": "Akaike", "name": null }, { "creator_type": "author", "first_name": "Tomohiro", "last_name": "Sawa", "name": null }, { "creator_type": "author", "first_name": "Tomoaki", "last_name": "Ida", "name": null }, { "creator_type": "author", "first_name": "Shigemoto", "last_name": "Fujii", "name": null }, { "creator_type": "author", "first_name": "Hideshi", "last_name": "Ihara", "name": null }, { "creator_type": "author", "first_name": "Junichi", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Risa", "last_name": "Tsukuura", "name": null }, { "creator_type": "author", "first_name": "Daichi", "last_name": "Chikazu", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Mishima", "name": null }, { "creator_type": "author", "first_name": "Kazuyoshi", "last_name": "Baba", "name": null }, { "creator_type": "author", "first_name": "Ryutaro", "last_name": "Kamijo", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.freeradbiomed.2017.05.022" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "28559051" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Bone Development", "descriptor_ui": "D001846", "major_topic": false }, { "descriptor": "Cartilage", "descriptor_ui": "D002356", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Cell Proliferation", "descriptor_ui": "D049109", "major_topic": false }, { "descriptor": "Chondrocytes", "descriptor_ui": "D019902", "major_topic": false }, { "descriptor": "Cyclic GMP", "descriptor_ui": "D006152", "major_topic": false }, { "descriptor": "Fetus", "descriptor_ui": "D005333", "major_topic": false }, { "descriptor": "Growth Plate", "descriptor_ui": "D006132", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred ICR", "descriptor_ui": "D008813", "major_topic": false }, { "descriptor": "Natriuretic Peptide, C-Type", "descriptor_ui": "D020098", "major_topic": false }, { "descriptor": "Nitric Oxide", "descriptor_ui": "D009569", "major_topic": false }, { "descriptor": "Primary Cell Culture", "descriptor_ui": "D061251", "major_topic": false }, { "descriptor": "Tibia", "descriptor_ui": "D013977", "major_topic": false }, { "descriptor": "Tissue Culture Techniques", "descriptor_ui": "D046509", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Sep", "date_precision": "unknown", "issue": "", "normalized_date": null, "pages": "63-71", "proceedings_title": null, "publisher": "", "title": "Free radical biology & medicine", "volume": "110", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "8-Nitro-cGMP promotes bone growth through expansion of growth plate cartilage.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Platelet-derived growth factor (PDGF) is a key factor in angiogenesis; however, its role in adult obesity remains unclear. In order to clarify its pathophysiological role, we investigated the significance of PDGF receptor beta (PDGFRbeta) in adipose tissue expansion and glucose metabolism. Mature vessels in the epididymal white adipose tissue (eWAT) were tightly wrapped with pericytes in normal mice. Pericyte desorption from vessels and the subsequent proliferation of endothelial cells were markedly increased in the eWAT of diet-induced obese mice. Analyses with flow cytometry and adipose tissue cultures indicated that PDGF-B caused the detachment of pericytes from vessels in a concentration-dependent manner. M1-macrophages were a major type of cells expressing PDGF-B in obese adipose tissue. In contrast, pericyte detachment was attenuated and vascularity within eWAT was reduced in tamoxifen-inducible conditional Pdgfrb-knockout mice with decreases in adipocyte size and chronic inflammation. Furthermore, Pdgfrb-knockout mice showed enhanced energy expenditure. Consequently, diet-induced obesity and the associated deterioration of glucose metabolism in wild-type mice were absent in Pdgfrb-knockout mice. Therefore, PDGF-B-PDGFRbeta signaling plays a significant role in the development of adipose tissue neovascularization and appears to be a fundamental target for the prevention of obesity and type 2 diabetes.", "classifications": [ { "id": "Inaba", "label": "Group Inaba", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yasuhiro", "last_name": "Onogi", "name": null }, { "creator_type": "author", "first_name": "Tsutomu", "last_name": "Wada", "name": null }, { "creator_type": "author", "first_name": "Chie", "last_name": "Kamiya", "name": null }, { "creator_type": "author", "first_name": "Kento", "last_name": "Inata", "name": null }, { "creator_type": "author", "first_name": "Takatoshi", "last_name": "Matsuzawa", "name": null }, { "creator_type": "author", "first_name": "Yuka", "last_name": "Inaba", "name": null }, { "creator_type": "author", "first_name": "Kumi", "last_name": "Kimura", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Inoue", "name": null }, { "creator_type": "author", "first_name": "Seiji", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Yoko", "last_name": "Ishii", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Koya", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Tsuneki", "name": null }, { "creator_type": "author", "first_name": "Masakiyo", "last_name": "Sasahara", "name": null }, { "creator_type": "author", "first_name": "Toshiyasu", "last_name": "Sasaoka", "name": null } ], "identifiers": { "doi": { "normalized": "10.2337/db16-0881" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "28122789" } }, "mesh": [ { "descriptor": "Adipose Tissue", "descriptor_ui": "D000273", "major_topic": false }, { "descriptor": "Adipose Tissue, White", "descriptor_ui": "D052436", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Blotting, Western", "descriptor_ui": "D015153", "major_topic": false }, { "descriptor": "Cell Proliferation", "descriptor_ui": "D049109", "major_topic": false }, { "descriptor": "Diet, High-Fat", "descriptor_ui": "D059305", "major_topic": false }, { "descriptor": "Endothelial Cells", "descriptor_ui": "D042783", "major_topic": false }, { "descriptor": "Flow Cytometry", "descriptor_ui": "D005434", "major_topic": false }, { "descriptor": "Glucose", "descriptor_ui": "D005947", "major_topic": false }, { "descriptor": "Glucose Clamp Technique", "descriptor_ui": "D015309", "major_topic": false }, { "descriptor": "Macrophages", "descriptor_ui": "D008264", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Mice, Transgenic", "descriptor_ui": "D008822", "major_topic": false }, { "descriptor": "Neovascularization, Pathologic", "descriptor_ui": "D009389", "major_topic": false }, { "descriptor": "Obesity", "descriptor_ui": "D009765", "major_topic": false }, { "descriptor": "Pericytes", "descriptor_ui": "D020286", "major_topic": false }, { "descriptor": "Proto-Oncogene Proteins c-sis", "descriptor_ui": "D020574", "major_topic": false }, { "descriptor": "Real-Time Polymerase Chain Reaction", "descriptor_ui": "D060888", "major_topic": false }, { "descriptor": "Receptor, Platelet-Derived Growth Factor beta", "descriptor_ui": "D020797", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Vascular Remodeling", "descriptor_ui": "D066253", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Apr", "date_precision": "unknown", "issue": "4", "normalized_date": null, "pages": "1008-1021", "proceedings_title": null, "publisher": "", "title": "Diabetes", "volume": "66", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "PDGFRbeta Regulates Adipose Tissue Expansion and Glucose Metabolism via Vascular Remodeling in Diet-Induced Obesity.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: Oxidative stress is a major aetiological factor driving chronic obstructive pulmonary disease (COPD). Recently recognised as potent antioxidants, reactive persulfide and polysulfide species are biosynthesised by cystathionine beta-synthase and cystathionine gamma-lyase. The production of reactive persulfide and polysulfide species in the lungs of patients with COPD remain unknown. OBJECTIVES: The aim of this study was to examine the production of reactive persulfides and polysulfides, such as glutathione persulfide (GSSH), cysteine persulfide (CysSSH) and glutathione trisulfide (GSSSH), in lung-resident cells and epithelial lining fluid (ELF) obtained from patients with mild to moderate COPD. METHODS: Lung tissues, primary lung cells, ELF and sputum were obtained. The amounts of reactive persulfides and polysulfides in the cells and ELF were measured by liquid chromatography-tandem mass spectrometry with beta-(4-hydroxyphenyl) ethyl iodoacetamide as a trapping agent for hydroper/polysulfides. The amounts of synthases in the lung tissues, sputum and primary cells were quantified. RESULTS: The amounts of GSSH, CysSSH and GSSSH were decreased in the lung cells and ELF from patients with COPD. The amounts of reactive persulfides and polysulfides in the lung cells had a positive correlation with the degree of airflow limitation. By contrast, the amounts of the synthases were increased in the lung tissues and sputum cells of patients with COPD. CONCLUSIONS: We have identified a decrease in reactive persulfide and polysulfide species in the lungs of patients with COPD. These data suggest that the newly detected antioxidants reactive persulfides and polysulfides could be associated with the redox balance in the lungs of patients with COPD.", "classifications": [ { "id": "Akaike", "label": "Group Akaike", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Tadahisa", "last_name": "Numakura", "name": null }, { "creator_type": "author", "first_name": "Hisatoshi", "last_name": "Sugiura", "name": null }, { "creator_type": "author", "first_name": "Takaaki", "last_name": "Akaike", "name": null }, { "creator_type": "author", "first_name": "Tomoaki", "last_name": "Ida", "name": null }, { "creator_type": "author", "first_name": "Shigemoto", "last_name": "Fujii", "name": null }, { "creator_type": "author", "first_name": "Akira", "last_name": "Koarai", "name": null }, { "creator_type": "author", "first_name": "Mitsuhiro", "last_name": "Yamada", "name": null }, { "creator_type": "author", "first_name": "Katsuhiro", "last_name": "Onodera", "name": null }, { "creator_type": "author", "first_name": "Yuichiro", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Rie", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Kei", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Yutaka", "last_name": "Shishikura", "name": null }, { "creator_type": "author", "first_name": "Taizou", "last_name": "Hirano", "name": null }, { "creator_type": "author", "first_name": "Satoru", "last_name": "Yanagisawa", "name": null }, { "creator_type": "author", "first_name": "Naoya", "last_name": "Fujino", "name": null }, { "creator_type": "author", "first_name": "Tatsuma", "last_name": "Okazaki", "name": null }, { "creator_type": "author", "first_name": "Tsutomu", "last_name": "Tamada", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Hoshikawa", "name": null }, { "creator_type": "author", "first_name": "Yoshinori", "last_name": "Okada", "name": null }, { "creator_type": "author", "first_name": "Masakazu", "last_name": "Ichinose", "name": null } ], "identifiers": { "doi": { "normalized": "10.1136/thoraxjnl-2016-209359" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "28724639" } }, "mesh": [ { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Antioxidants", "descriptor_ui": "D000975", "major_topic": false }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Chemokines", "descriptor_ui": "D018925", "major_topic": false }, { "descriptor": "Cysteine", "descriptor_ui": "D003545", "major_topic": false }, { "descriptor": "Cytokines", "descriptor_ui": "D016207", "major_topic": false }, { "descriptor": "Disulfides", "descriptor_ui": "D004220", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Forced Expiratory Volume", "descriptor_ui": "D005541", "major_topic": false }, { "descriptor": "Glutathione", "descriptor_ui": "D005978", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Inflammation Mediators", "descriptor_ui": "D018836", "major_topic": false }, { "descriptor": "Lung", "descriptor_ui": "D008168", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Oxidative Stress", "descriptor_ui": "D018384", "major_topic": false }, { "descriptor": "Pulmonary Disease, Chronic Obstructive", "descriptor_ui": "D029424", "major_topic": false }, { "descriptor": "Reactive Oxygen Species", "descriptor_ui": "D017382", "major_topic": false }, { "descriptor": "Smoking", "descriptor_ui": "D012907", "major_topic": false }, { "descriptor": "Sputum", "descriptor_ui": "D013183", "major_topic": false }, { "descriptor": "Sulfides", "descriptor_ui": "D013440", "major_topic": false }, { "descriptor": "Vital Capacity", "descriptor_ui": "D014797", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Dec", "date_precision": "unknown", "issue": "12", "normalized_date": null, "pages": "1074-1083", "proceedings_title": null, "publisher": "", "title": "Thorax", "volume": "72", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Production of reactive persulfide species in chronic obstructive pulmonary disease.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Voltage‐dependent anion channel 1 (VDAC1), which is located in the outer mitochondrial membrane, plays important roles in various cellular processes. For example, oligomerization of VDAC1 is involved in the release of cytochrome c to the cytoplasm, leading to apoptosis. However, it is unknown how VDAC1 oligomerization occurs in the membrane. In the present study, we determined high‐resolution crystal structures of oligomeric human VDAC1 (hVDAC1) prepared by using an Escherichia coli cell‐free protein synthesis system, which avoided the need for denaturation and refolding of the protein. Broad‐range screening using a bicelle crystallization method produced crystals in space groups C222 and P22121, which diffracted to a resolution of 3.10 and 3.15 Å, respectively. Each crystal contained two hVDAC1 protomers in the asymmetric unit. Dimer within the asymmetrical unit of the crystal in space group C222 were oriented parallel, whereas those of the crystal in space group P22121 were oriented anti‐parallel. From a model of the crystal in space group C222, which we constructed by using crystal symmetry operators, a heptameric structure with eight patterns of interaction between protomers, including hydrophobic interactions with β‐strands, hydrophilic interactions with loop regions, and protein–lipid interactions, was observed. It is possible that by having multiple patterns of interaction, VDAC1 can form homo‐ or hetero‐oligomers not only with other VDAC1 protomers but also with other proteins such as VDAC2, VDAC3 and apoptosis‐regulating proteins in the Bcl‐2 family.", "classifications": [ { "id": "Sodeoka", "label": "Group Sodeoka", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Toshiaki", "last_name": "Hosaka", "name": null }, { "creator_type": "author", "first_name": "Masateru", "last_name": "Okazaki", "name": null }, { "creator_type": "author", "first_name": "Tomomi", "last_name": "Kimura‐Someya", "name": null }, { "creator_type": "author", "first_name": "Yoshiko", "last_name": "Ishizuka‐Katsura", "name": null }, { "creator_type": "author", "first_name": "Kaori", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Shigeyuki", "last_name": "Yokoyama", "name": null }, { "creator_type": "author", "first_name": "Kosuke", "last_name": "Dodo", "name": null }, { "creator_type": "author", "first_name": "Mikiko", "last_name": "Sodeoka", "name": null }, { "creator_type": "author", "first_name": "Mikako", "last_name": "Shirouzu", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/pro.3211" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "28608415" } }, "mesh": [ { "descriptor": "Crystallography, X-Ray", "descriptor_ui": "D018360", "major_topic": false }, { "descriptor": "Escherichia coli", "descriptor_ui": "D004926", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Hydrophobic and Hydrophilic Interactions", "descriptor_ui": "D057927", "major_topic": false }, { "descriptor": "Lipid Bilayers", "descriptor_ui": "D008051", "major_topic": false }, { "descriptor": "Models, Molecular", "descriptor_ui": "D008958", "major_topic": false }, { "descriptor": "Protein Multimerization", "descriptor_ui": "D055503", "major_topic": false }, { "descriptor": "Protein Subunits", "descriptor_ui": "D021122", "major_topic": false }, { "descriptor": "Recombinant Proteins", "descriptor_ui": "D011994", "major_topic": false }, { "descriptor": "Surface Properties", "descriptor_ui": "D013499", "major_topic": false }, { "descriptor": "Voltage-Dependent Anion Channel 1", "descriptor_ui": "D050995", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Sep", "date_precision": "unknown", "issue": "9", "normalized_date": null, "pages": "1749-1758", "proceedings_title": null, "publisher": "", "title": "Protein Science : A Publication of the Protein Society", "volume": "26", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Crystal structural characterization reveals novel oligomeric interactions of human voltage‐dependent anion channel 1.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: A family history of gastric cancer (GC) is a well-known risk factor of GC. Genetic variations in genes of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) have been related to the risk of GC, but their association with familial background is not clear. We investigated whether individuals with a multiple family history of GC have more risk genotypes of MMP/TIMP genes. METHODS: We genotyped ten common functional polymorphisms of MMP/TIMP genes in 4427 individuals aged 35-69 years without a history of GC who were enrolled in the Japan Multi-institutional Collaborative Cohort Study. Individuals who have two or more first-degree relatives (parents and siblings) with GC were categorized as having a multiple family history. Odds ratios (ORs) for multiple family history compared with no family history were calculated. RESULTS: MMP9 279QQ (rs17576) was more frequently observed in individuals whose both parents had a history of GC (n = 23) and in individuals for whom one parent and their sibling(s) had a history of GC (n = 36) compared with those with no family history (n = 3816) [30.4 % vs 11.6 %, OR 4.34, 95 % confidence interval (CI) 1.45-13.03 and 16.7 % vs 11.6 %, OR 2.26, 95 % CI 0.81-6.27 after adjustment for age, sex, and current smoking]. The population attributable fraction was 38.1 %. The haplotype MMP9-1562C/279Q/668Q was more frequently observed in individuals whose both parents had a history of GC and in individuals for whom one parent and their sibling(s) had a history of GC compared with those with no family history (OR 3.35, 95 % CI 0.75-14.96 and OR 3.51, 95 % CI 1.35-9.15 respectively). CONCLUSIONS: MMP9 polymorphisms were associated with a multiple family history of GC. Screening for these genotypes together with familial background may help us to identify individuals at an increased risk of GC.", "classifications": [ { "id": "Tanaka", "label": "Group Tanaka", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Rieko", "last_name": "Okada", "name": null }, { "creator_type": "author", "first_name": "Mariko", "last_name": "Naito", "name": null }, { "creator_type": "author", "first_name": "Yuta", "last_name": "Hattori", "name": null }, { "creator_type": "author", "first_name": "Toshio", "last_name": "Seiki", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Wakai", "name": null }, { "creator_type": "author", "first_name": "Hinako", "last_name": "Nanri", "name": null }, { "creator_type": "author", "first_name": "Miki", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Sadao", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Tara Sefanya", "last_name": "Kairupan", "name": null }, { "creator_type": "author", "first_name": "Naoyuki", "last_name": "Takashima", "name": null }, { "creator_type": "author", "first_name": "Haruo", "last_name": "Mikami", "name": null }, { "creator_type": "author", "first_name": "Keizo", "last_name": "Ohnaka", "name": null }, { "creator_type": "author", "first_name": "Yoshiyuki", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Sakurako", "last_name": "Katsuura-Kamano", "name": null }, { "creator_type": "author", "first_name": "Michiaki", "last_name": "Kubo", "name": null }, { "creator_type": "author", "first_name": "Nobuyuki", "last_name": "Hamajima", "name": null }, { "creator_type": "author", "first_name": "Hideo", "last_name": "Tanaka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/s10120-016-0608-2" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "27053167" } }, "mesh": [ { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Biomarkers, Tumor", "descriptor_ui": "D014408", "major_topic": false }, { "descriptor": "Cohort Studies", "descriptor_ui": "D015331", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Follow-Up Studies", "descriptor_ui": "D005500", "major_topic": false }, { "descriptor": "Genetic Predisposition to Disease", "descriptor_ui": "D020022", "major_topic": true }, { "descriptor": "Genotype", "descriptor_ui": "D005838", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Matrix Metalloproteinase 9", "descriptor_ui": "D020780", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Polymorphism, Single Nucleotide", "descriptor_ui": "D020641", "major_topic": false }, { "descriptor": "Prognosis", "descriptor_ui": "D011379", "major_topic": false }, { "descriptor": "Risk Factors", "descriptor_ui": "D012307", "major_topic": false }, { "descriptor": "Stomach Neoplasms", "descriptor_ui": "D013274", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Mar", "date_precision": "unknown", "issue": "2", "normalized_date": null, "pages": "246-253", "proceedings_title": null, "publisher": "", "title": "Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association", "volume": "20", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Matrix metalloproteinase 9 gene polymorphisms are associated with a multiple family history of gastric cancer.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Osteoporosis is characterized as a metabolic disorder of bone tissue, and various metabolic markers are now available to support its diagnosis and evaluate treatment effects. Substances produced as end products of metabolomic activities are the correlated factors to the biological or metabolic status, and thus, metabolites are considered highly sensitive markers of particular pathological states, including osteoporosis. Here we undertook comprehensive serum metabolomics analysis in postmenopausal women with or without low bone mineral density (low BMD vs controls) for the first time using capillary electrophoresis/mass spectrometry. Among the metabolites tested, 57 were detected in sera. Levels of hydroxyproline, Gly-Gly and cystine, differed significantly between groups, with Gly-Gly and cystine significantly lower in the low BMD group and hydroxyproline, a reported marker of osteoporosis, significantly higher. Levels of TRACP5b, a bone resorption marker, were significantly higher in the low BMD group, supporting the study's validity. Taken together, our findings represent novel metabolomic profiling in low BMD in postmenopausal women.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Takeshi", "last_name": "Miyamoto", "name": null }, { "creator_type": "author", "first_name": "Akiyoshi", "last_name": "Hirayama", "name": null }, { "creator_type": "author", "first_name": "Yuiko", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Tami", "last_name": "Koboyashi", "name": null }, { "creator_type": "author", "first_name": "Eri", "last_name": "Katsuyama", "name": null }, { "creator_type": "author", "first_name": "Hiroya", "last_name": "Kanagawa", "name": null }, { "creator_type": "author", "first_name": "Hiroya", "last_name": "Miyamoto", "name": null }, { "creator_type": "author", "first_name": "Tomoaki", "last_name": "Mori", "name": null }, { "creator_type": "author", "first_name": "Shigeyuki", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Atsuhiro", "last_name": "Fujie", "name": null }, { "creator_type": "author", "first_name": "Mayu", "last_name": "Morita", "name": null }, { "creator_type": "author", "first_name": "Ryuichi", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Toshimi", "last_name": "Tando", "name": null }, { "creator_type": "author", "first_name": "Kana", "last_name": "Miyamoto", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Tsuji", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Funayama", "name": null }, { "creator_type": "author", "first_name": "Masaya", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Morio", "last_name": "Matsumoto", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Masaru", "last_name": "Tomita", "name": null }, { "creator_type": "author", "first_name": "Yoshiaki", "last_name": "Toyama", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.bone.2016.10.027" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "27989648" } }, "mesh": [ { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Bone Density", "descriptor_ui": "D015519", "major_topic": true }, { "descriptor": "Case-Control Studies", "descriptor_ui": "D016022", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Metabolome", "descriptor_ui": "D055442", "major_topic": false }, { "descriptor": "Metabolomics", "descriptor_ui": "D055432", "major_topic": true }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Postmenopause", "descriptor_ui": "D017698", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Feb", "date_precision": "unknown", "issue": "", "normalized_date": null, "pages": "1-4", "proceedings_title": null, "publisher": "", "title": "Bone", "volume": "95", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "A serum metabolomics-based profile in low bone mineral density postmenopausal women.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Cell competition is a phenomenon originally described as the competition between cell populations with different genetic backgrounds; losing cells with lower fitness are eliminated. With the progress in identification of related molecules, some reports described the relevance of cell mechanics during elimination. Furthermore, recent live imaging studies have shown that even in tissues composed of genetically identical cells, a non-negligible number of cells are eliminated during growth. Thus, mechanical cell elimination (MCE) as a consequence of mechanical cellular interactions is an unavoidable event in growing tissues and a commonly observed phenomenon. Here, we studied MCE in a genetically-homogeneous tissue from the perspective of tissue growth efficiency and homeostasis. First, we propose two quantitative measures, cell and tissue fitness, to evaluate cellular competitiveness and tissue growth efficiency, respectively. By mechanical tissue simulation in a pure population where all cells have the same mechanical traits, we clarified the dependence of cell elimination rate or cell fitness on different mechanical/growth parameters. In particular, we found that geometrical (specifically, cell size) and mechanical (stress magnitude) heterogeneities are common determinants of the elimination rate. Based on these results, we propose possible mechanical feedback mechanisms that could improve tissue growth efficiency and density/stress homeostasis. Moreover, when cells with different mechanical traits are mixed (e.g., in the presence of phenotypic variation), we show that MCE could drive a drastic shift in cell trait distribution, thereby improving tissue growth efficiency through the selection of cellular traits, i.e. intra-tissue \"evolution\". Along with the improvement of growth efficiency, cell density, stress state, and phenotype (mechanical traits) were also shown to be homogenized through growth. More theoretically, we propose a mathematical model that approximates cell competition dynamics, by which the time evolution of tissue fitness and cellular trait distribution can be predicted without directly simulating a cell-based mechanical model.", "classifications": [ { "id": "Morishita", "label": "Group Morishita", "parent": "Morishita", "type": "group" }, { "id": "Morishita", "label": "Team Morishita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Sang-Woo", "last_name": "Lee", "name": null }, { "creator_type": "author", "first_name": "Yoshihiro", "last_name": "Morishita", "name": null } ], "identifiers": { "doi": { "normalized": "10.1371/journal.pcbi.1005651" }, "pmcid": { "normalized": "PMC5547694" }, "pmid": { "normalized": "28704373" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Biological Phenomena", "descriptor_ui": "D001686", "major_topic": true }, { "descriptor": "Biomechanical Phenomena", "descriptor_ui": "D001696", "major_topic": false }, { "descriptor": "Cell Physiological Phenomena", "descriptor_ui": "D002468", "major_topic": false }, { "descriptor": "Computational Biology", "descriptor_ui": "D019295", "major_topic": false }, { "descriptor": "Drosophila", "descriptor_ui": "D004330", "major_topic": false }, { "descriptor": "Epithelium", "descriptor_ui": "D004848", "major_topic": false }, { "descriptor": "Genetic Fitness", "descriptor_ui": "D056084", "major_topic": true }, { "descriptor": "Homeostasis", "descriptor_ui": "D006706", "major_topic": false }, { "descriptor": "Models, Biological", "descriptor_ui": "D008954", "major_topic": false }, { "descriptor": "Plant Development", "descriptor_ui": "D063245", "major_topic": false }, { "descriptor": "Xenopus", "descriptor_ui": "D014981", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Jul", "date_precision": "unknown", "issue": "7", "normalized_date": null, "pages": "e1005651", "proceedings_title": null, "publisher": "", "title": "PLoS computational biology", "volume": "13", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Possible roles of mechanical cell elimination intrinsic to growing tissues from the perspective of tissue growth efficiency and homeostasis.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "INTRODUCTION: The current WHO classification of lung cancer states that a diagnosis of SCLC can be reliably made on routine histological and cytological grounds but immunohistochemistry (IHC) may be required, particularly (1) in cases in which histologic features are equivocal and (2) in cases in which the pathologist wants to increase confidence in diagnosis. However, reproducibility studies based on hematoxylin and eosin-stained slides alone for SCLC versus large cell neuroendocrine carcinoma (LCNEC) have shown pairwise kappa scores ranging from 0.35 to 0.81. This study examines whether judicious use of IHC improves diagnostic reproducibility for SCLC. METHODS: Nineteen lung pathologists studied interactive digital images of 79 tumors, predominantly neuroendocrine lung tumors. Images of resection and biopsy specimens were used to make diagnoses solely on the basis of morphologic features (level 1), morphologic features along with requested IHC staining results (level 2), and all available IHC staining results (level 3). RESULTS: For the 19 pathologists reading all 79 cases, the rate of agreement for level 1 was 64.7%, and it increased to 73.2% and 77.5% in levels 2 and 3, respectively. With IHC, kappa scores for four tumor categories (SCLC, LCNEC, carcinoid tumors, and other) increased in resection samples from 0.43 to 0.60 and in biopsy specimens from 0.43 to 0.64. CONCLUSIONS: Diagnosis using hematoxylin and eosin staining alone showeds moderate agreement among pathologists in tumors with neuroendocrine morphology, but agreement improved to good in most cases with the judicious use of IHC, especially in the diagnosis of SCLC. An approach for IHC in the differential diagnosis of SCLC is provided.", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Erik", "last_name": "Thunnissen", "name": null }, { "creator_type": "author", "first_name": "Alain C.", "last_name": "Borczuk", "name": null }, { "creator_type": "author", "first_name": "Douglas B.", "last_name": "Flieder", "name": null }, { "creator_type": "author", "first_name": "Birgit", "last_name": "Witte", "name": null }, { "creator_type": "author", "first_name": "Mary Beth", "last_name": "Beasley", "name": null }, { "creator_type": "author", "first_name": "Jin-Haeng", "last_name": "Chung", "name": null }, { "creator_type": "author", "first_name": "Sanja", "last_name": "Dacic", "name": null }, { "creator_type": "author", "first_name": "Sylvie", "last_name": "Lantuejoul", "name": null }, { "creator_type": "author", "first_name": "Prudence A.", "last_name": "Russell", "name": null }, { "creator_type": "author", "first_name": "Michael", "last_name": "den Bakker", "name": null }, { "creator_type": "author", "first_name": "Johan", "last_name": "Botling", "name": null }, { "creator_type": "author", "first_name": "Elisabeth", "last_name": "Brambilla", "name": null }, { "creator_type": "author", "first_name": "Erienne", "last_name": "de Cuba", "name": null }, { "creator_type": "author", "first_name": "Kim R.", "last_name": "Geisinger", "name": null }, { "creator_type": "author", "first_name": "Kenzo", "last_name": "Hiroshima", "name": null }, { "creator_type": "author", "first_name": "Alberto M.", "last_name": "Marchevsky", "name": null }, { "creator_type": "author", "first_name": "Yuko", "last_name": "Minami", "name": null }, { "creator_type": "author", "first_name": "Andre", "last_name": "Moreira", "name": null }, { "creator_type": "author", "first_name": "Andrew G.", "last_name": "Nicholson", "name": null }, { "creator_type": "author", "first_name": "Akihiko", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Ming-Sound", "last_name": "Tsao", "name": null }, { "creator_type": "author", "first_name": "Arne", "last_name": "Warth", "name": null }, { "creator_type": "author", "first_name": "Edwina", "last_name": "Duhig", "name": null }, { "creator_type": "author", "first_name": "Gang", "last_name": "Chen", "name": null }, { "creator_type": "author", "first_name": "Yoshihiro", "last_name": "Matsuno", "name": null }, { "creator_type": "author", "first_name": "William D.", "last_name": "Travis", "name": null }, { "creator_type": "author", "first_name": "Kelly", "last_name": "Butnor", "name": null }, { "creator_type": "author", "first_name": "Wendy", "last_name": "Cooper", "name": null }, { "creator_type": "author", "first_name": "Mari", "last_name": "Mino-Kenudson", "name": null }, { "creator_type": "author", "first_name": "Noriko", "last_name": "Motoi", "name": null }, { "creator_type": "author", "first_name": "Claudia", "last_name": "Poleri", "name": null }, { "creator_type": "author", "first_name": "Giuseppe", "last_name": "Pelosi", "name": null }, { "creator_type": "author", "first_name": "Keith", "last_name": "Kerr", "name": null }, { "creator_type": "author", "first_name": "Seena C.", "last_name": "Aisner", "name": null }, { "creator_type": "author", "first_name": "Yuichi", "last_name": "Ishikawa", "name": null }, { "creator_type": "author", "first_name": "Reinhard H.", "last_name": "Buettner", "name": null }, { "creator_type": "author", "first_name": "Naoto", "last_name": "Keino", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null }, { "creator_type": "author", "first_name": "Masayuki", "last_name": "Noguchi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.jtho.2016.12.004" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "27998793" } }, "mesh": [ { "descriptor": "Adenocarcinoma", "descriptor_ui": "D000230", "major_topic": false }, { "descriptor": "Biomarkers, Tumor", "descriptor_ui": "D014408", "major_topic": false }, { "descriptor": "Carcinoma, Neuroendocrine", "descriptor_ui": "D018278", "major_topic": false }, { "descriptor": "Carcinoma, Non-Small-Cell Lung", "descriptor_ui": "D002289", "major_topic": false }, { "descriptor": "Carcinoma, Squamous Cell", "descriptor_ui": "D002294", "major_topic": false }, { "descriptor": "Diagnosis, Differential", "descriptor_ui": "D003937", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Immunoenzyme Techniques", "descriptor_ui": "D007124", "major_topic": false }, { "descriptor": "International Agencies", "descriptor_ui": "D007390", "major_topic": false }, { "descriptor": "Lung Neoplasms", "descriptor_ui": "D008175", "major_topic": false }, { "descriptor": "Neoplasm Staging", "descriptor_ui": "D009367", "major_topic": false }, { "descriptor": "Prognosis", "descriptor_ui": "D011379", "major_topic": false }, { "descriptor": "Reproducibility of Results", "descriptor_ui": "D015203", "major_topic": false }, { "descriptor": "Small Cell Lung Carcinoma", "descriptor_ui": "D055752", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Feb", "date_precision": "unknown", "issue": "2", "normalized_date": null, "pages": "334-346", "proceedings_title": null, "publisher": "", "title": "Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer", "volume": "12", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "The Use of Immunohistochemistry Improves the Diagnosis of Small Cell Lung Cancer and Its Differential Diagnosis. An International Reproducibility Study in a Demanding Set of Cases.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "A Markovian lattice model for photoreceptor cells is introduced to describe the growth of mosaic patterns on fish retina. The radial stripe pattern observed in wild-type zebrafish is shown to be selected naturally during retina growth, against the geometrically equivalent circular stripe pattern. The mechanism of such dynamical pattern selection is clarified on the basis of both numerical simulations and theoretical analyses, which find that the successive emergence of local defects plays a critical role in the realization of the wild-type pattern.", "classifications": [ { "id": "Mochizuki", "label": "Group Mochizuki", "parent": "Eiraku", "type": "group" }, { "id": "Eiraku", "label": "Team Eiraku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Noriaki", "last_name": "Ogawa", "name": null }, { "creator_type": "author", "first_name": "Tetsuo", "last_name": "Hatsuda", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Mochizuki", "name": null }, { "creator_type": "author", "first_name": "Masashi", "last_name": "Tachikawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1103/physreve.96.032416" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "29346954" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Computer Simulation", "descriptor_ui": "D003198", "major_topic": false }, { "descriptor": "Models, Biological", "descriptor_ui": "D008954", "major_topic": true }, { "descriptor": "Retina", "descriptor_ui": "D012160", "major_topic": false }, { "descriptor": "Zebrafish", "descriptor_ui": "D015027", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Sep", "date_precision": "unknown", "issue": "3-1", "normalized_date": null, "pages": "032416", "proceedings_title": null, "publisher": "", "title": "Physical review. E", "volume": "96", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Dynamical pattern selection of growing cellular mosaic in fish retina.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The current consensus is that environmental electrophiles activate redox signal transduction pathways through covalent modification of sensor proteins with reactive thiol groups at low concentrations, while they cause cell damage at higher concentrations. We previously exposed human carcinoma A431 cells to the atmospheric electrophile 1,4-naphthoquinone (1,4-NQ) and found that heat shock protein 90 (HSP90), a negative regulator of heat shock factor 1 (HSF1), was a target of 1,4-NQ. In the study presented here, we determined whether 1,4-NQ activates HSF1. We also examined whether such redox signaling could be regulated by nucleophilic sulfur species. Exposure of A431 cells to 1,4-NQ covalently modified cellular HSP90, resulting in repression of the association between HSF1 with HSP90, thereby enhancing HSF1 translocation into the nuclei. Liquid chromatography-tandem mass spectrometry analysis with recombinant HSP90 revealed that the modifications site were Cys412 and Cys564. We found that HSF1 activation mediated by 1,4-NQ upregulated downstream genes, such as HSPA6. HSF1 knockdown accelerated 1,4-NQ-mediated cytotoxicity in the cells. While simultaneous treatment with reactive persulfide and polysulfide, Na(2)S(2) and Na(2)S(4), blocked 1,4-NQ-dependent protein modification and HSF1 activation in A431 cells, the knockdown of Cys persulfide producing enzymes cystathionine beta-synthase (CBS) and/or cystathionine gamma-lyase (CSE) enhanced these phenomena. 1,4-NQ-thiol adduct and 1,4-NQ-S-1,4-NQ adduct were produced during the enzymatic reaction of recombinant CSE in the presence of 1,4-NQ. The results suggest that activation of the HSP90-HSF1 signal transduction pathway mediated by 1,4-NQ protects cells against 1,4-NQ and that per/polysulfides can diminish the reactivity of 1,4-NQ by forming sulfur adducts.", "classifications": [ { "id": "Akaike", "label": "Group Akaike", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yumi", "last_name": "Abiko", "name": null }, { "creator_type": "author", "first_name": "Liang", "last_name": "Sha", "name": null }, { "creator_type": "author", "first_name": "Yasuhiro", "last_name": "Shinkai", "name": null }, { "creator_type": "author", "first_name": "Takamitsu", "last_name": "Unoki", "name": null }, { "creator_type": "author", "first_name": "Nho Cong", "last_name": "Luong", "name": null }, { "creator_type": "author", "first_name": "Yukihiro", "last_name": "Tsuchiya", "name": null }, { "creator_type": "author", "first_name": "Yasuo", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Reiko", "last_name": "Hirose", "name": null }, { "creator_type": "author", "first_name": "Takaaki", "last_name": "Akaike", "name": null }, { "creator_type": "author", "first_name": "Yoshito", "last_name": "Kumagai", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.freeradbiomed.2016.12.047" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "28049024" } }, "mesh": [ { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Cell Nucleus", "descriptor_ui": "D002467", "major_topic": false }, { "descriptor": "Chromatography, Liquid", "descriptor_ui": "D002853", "major_topic": false }, { "descriptor": "Cysteine", "descriptor_ui": "D003545", "major_topic": false }, { "descriptor": "DNA-Binding Proteins", "descriptor_ui": "D004268", "major_topic": false }, { "descriptor": "Gene Expression Regulation", "descriptor_ui": "D005786", "major_topic": false }, { "descriptor": "Heat Shock Transcription Factors", "descriptor_ui": "D000076249", "major_topic": false }, { "descriptor": "HSP70 Heat-Shock Proteins", "descriptor_ui": "D018840", "major_topic": false }, { "descriptor": "HSP90 Heat-Shock Proteins", "descriptor_ui": "D018841", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Naphthoquinones", "descriptor_ui": "D009285", "major_topic": false }, { "descriptor": "Oxidation-Reduction", "descriptor_ui": "D010084", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Sulfhydryl Compounds", "descriptor_ui": "D013438", "major_topic": false }, { "descriptor": "Sulfur", "descriptor_ui": "D013455", "major_topic": false }, { "descriptor": "Tandem Mass Spectrometry", "descriptor_ui": "D053719", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Mar", "date_precision": "unknown", "issue": "", "normalized_date": null, "pages": "118-128", "proceedings_title": null, "publisher": "", "title": "Free radical biology & medicine", "volume": "104", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "1,4-Naphthoquinone activates the HSP90/HSF1 pathway through the S-arylation of HSP90 in A431 cells: Negative regulation of the redox signal transduction pathway by persulfides/polysulfides.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Vacuolar (H(+) )-ATPases (V-ATPases) have important roles in the supply of nutrients to tumors by mediating autophagy and the endocytic uptake of extracellular fluids. Accordingly, V-ATPases are attractive therapeutic targets for cancer. However, the clinical use of V-ATPase inhibitors as anticancer drugs has not been realized, possibly owing to their high toxicity in humans. Inhibition of V-ATPase may be an appropriate strategy in highly susceptible cancers. In this study, we explored markers of V-ATPase inhibitor sensitivity. V-ATPase inhibitors led to pH impairment in acidic intracellular compartments, suppression of macropinocytosis, and decreased intracellular amino acid levels. The sensitivity of cells to V-ATPase inhibitors was correlated with low cathepsin D expression, and cancer cells showed increased sensitivity to V-ATPase inhibitors after pretreatment with a cathepsin D inhibitor and siRNA targeting the cathepsin D gene (CTSD). In addition, V-ATPase inhibitor treatment led to the induction of the amino acid starvation response, upregulation of endoplasmic reticulum stress markers, and suppression of mammalian target of rapamycin (mTOR) signaling in cells expressing low levels of cathepsin D. Some colorectal cancer patients showed the downregulation of cathepsin D in tumor tissues compared with matched normal tissues. These findings indicate that V-ATPase inhibitors are promising therapeutic options for cancers with downregulated cathepsin D.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Satoshi", "last_name": "Kitazawa", "name": null }, { "creator_type": "author", "first_name": "Satoru", "last_name": "Nishizawa", "name": null }, { "creator_type": "author", "first_name": "Hideyuki", "last_name": "Nakagawa", "name": null }, { "creator_type": "author", "first_name": "Masaaki", "last_name": "Funata", "name": null }, { "creator_type": "author", "first_name": "Kazuho", "last_name": "Nishimura", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Takahito", "last_name": "Hara", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/cas.13240" }, "pmcid": { "normalized": "PMC5480082" }, "pmid": { "normalized": "28317223" } }, "mesh": [ { "descriptor": "Antineoplastic Agents", "descriptor_ui": "D000970", "major_topic": false }, { "descriptor": "Autophagy", "descriptor_ui": "D001343", "major_topic": false }, { "descriptor": "Cathepsin D", "descriptor_ui": "D002402", "major_topic": false }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Down-Regulation", "descriptor_ui": "D015536", "major_topic": false }, { "descriptor": "Endoplasmic Reticulum Stress", "descriptor_ui": "D059865", "major_topic": false }, { "descriptor": "HCT116 Cells", "descriptor_ui": "D045325", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Neoplasms", "descriptor_ui": "D009369", "major_topic": false }, { "descriptor": "RNA, Small Interfering", "descriptor_ui": "D034741", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "TOR Serine-Threonine Kinases", "descriptor_ui": "D058570", "major_topic": false }, { "descriptor": "Up-Regulation", "descriptor_ui": "D015854", "major_topic": false }, { "descriptor": "Vacuolar Proton-Translocating ATPases", "descriptor_ui": "D025262", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Jun", "date_precision": "unknown", "issue": "6", "normalized_date": null, "pages": "1185-1193", "proceedings_title": null, "publisher": "", "title": "Cancer science", "volume": "108", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Cancer with low cathepsin D levels is susceptible to vacuolar (H(+) )-ATPase inhibition.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The reduction and binding of copper ions to the Cys/Trp motif, which is characterized by two cysteines and two tryptophans, in the extracellular N-terminal domain of the copper transporter (Ctr) protein of fungi are investigated using the model peptides of Ctr4 and Ctr5 from Schizosaccharomyces pombe. The Cys/Trp motif of Ctr5 can reduce Cu(II) and ligate Cu(I), which is the same as that of Ctr4 previously reported. Titration of Cu(II) and Cu(I) ions indicates that both the Cys/Trp motifs of Ctr4 and Ctr5 reduce two Cu(II) and bind two Cu(I) per one peptide. However, the coordination structure of the Cu(I)-peptide complex differs between Ctr4 and Ctr5. Cu(I) is bound to the Cys/Trp motif of Ctr5 via cysteine thiolate-Cu(I) bonds and cation-pi interaction with tryptophan, as reported for Ctr4, and a histidine residue in the Cys/Trp motif of Ctr5 is suggested to interact with Cu(I) via its Ntau atom. Ctr4 and Ctr5 exhibit a heterotrimeric form within cell membranes and the copper transport mechanism of the Ctr4/Ctr5 heterotrimer is discussed along with quantitative evaluation of the Cu(I)-binding constant of the Cys/Trp motif.", "classifications": [ { "id": "Nakabayashi", "label": "Group Nakabayashi", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Mariko", "last_name": "Okada", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Miura", "name": null }, { "creator_type": "author", "first_name": "Takakazu", "last_name": "Nakabayashi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.jinorgbio.2017.01.009" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "28167404" } }, "mesh": [ { "descriptor": "Amino Acid Motifs", "descriptor_ui": "D020816", "major_topic": false }, { "descriptor": "Cation Transport Proteins", "descriptor_ui": "D027682", "major_topic": false }, { "descriptor": "Copper", "descriptor_ui": "D003300", "major_topic": false }, { "descriptor": "Cysteine", "descriptor_ui": "D003545", "major_topic": false }, { "descriptor": "Metallochaperones", "descriptor_ui": "D056511", "major_topic": false }, { "descriptor": "Models, Biological", "descriptor_ui": "D008954", "major_topic": false }, { "descriptor": "Protein Domains", "descriptor_ui": "D000072417", "major_topic": false }, { "descriptor": "Schizosaccharomyces pombe Proteins", "descriptor_ui": "D029702", "major_topic": false }, { "descriptor": "Tryptophan", "descriptor_ui": "D014364", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Apr", "date_precision": "unknown", "issue": "", "normalized_date": null, "pages": "97-105", "proceedings_title": null, "publisher": "", "title": "Journal of inorganic biochemistry", "volume": "169", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Comparison of extracellular Cys/Trp motif between Schizosaccharomyces pombe Ctr4 and Ctr5.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Adaptation in a fluctuating environment is a process of fueling environmental information to gain fitness. Living systems have gradually developed strategies for adaptation from random and passive diversification of the phenotype to more proactive decision making, in which environmental information is sensed and exploited more actively and effectively. Understanding the fundamental relation between fitness and information is therefore crucial to clarify the limits and universal properties of adaptation. In this work, we elucidate the underlying stochastic and information-thermodynamic structure in this process, by deriving causal fluctuation relations (FRs) of fitness and information. Combined with a duality between phenotypic and environmental dynamics, the FRs reveal the limit of fitness gain, the relation of time reversibility with the achievability of the limit, and the possibility and condition for gaining excess fitness due to environmental fluctuation. The loss of fitness due to causal constraints and the limited capacity of real organisms is shown to be the difference between time-forward and time-backward path probabilities of phenotypic and environmental dynamics. Furthermore, the FRs generalize the concept of the evolutionary stable state (ESS) for fluctuating environment by giving the probability that the optimal strategy on average can be invaded by a suboptimal one owing to rare environmental fluctuation. These results clarify the information-thermodynamic structures in adaptation and evolution.", "classifications": [ { "id": "Kobayashi", "label": "Group Kobayashi", "parent": "Wakamoto", "type": "group" }, { "id": "Wakamoto", "label": "Team Wakamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Tetsuya J.", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Sughiyama", "name": null } ], "identifiers": { "doi": { "normalized": "10.1103/physreve.96.012402" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "29347239" } }, "mesh": [ { "descriptor": "Adaptation, Biological", "descriptor_ui": "D000220", "major_topic": false }, { "descriptor": "Biological Evolution", "descriptor_ui": "D005075", "major_topic": false }, { "descriptor": "Computer Simulation", "descriptor_ui": "D003198", "major_topic": false }, { "descriptor": "Environment", "descriptor_ui": "D004777", "major_topic": true }, { "descriptor": "Genetic Fitness", "descriptor_ui": "D056084", "major_topic": false }, { "descriptor": "Models, Biological", "descriptor_ui": "D008954", "major_topic": true }, { "descriptor": "Phenotype", "descriptor_ui": "D010641", "major_topic": false }, { "descriptor": "Population Dynamics", "descriptor_ui": "D011157", "major_topic": true }, { "descriptor": "Probability", "descriptor_ui": "D011336", "major_topic": false }, { "descriptor": "Stochastic Processes", "descriptor_ui": "D013269", "major_topic": false }, { "descriptor": "Thermodynamics", "descriptor_ui": "D013816", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Jul", "date_precision": "unknown", "issue": "1-1", "normalized_date": null, "pages": "012402", "proceedings_title": null, "publisher": "", "title": "Physical review. E", "volume": "96", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Stochastic and information-thermodynamic structures of population dynamics in a fluctuating environment.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "In cells, the molecular constituents of membranes are dynamically turned over by transportation from one membrane to another. This molecular turnover causes the membrane to shrink or expand by sensing the stress state within the cell, changing its morphology. At present, little is known as to how this turnover regulates the dynamic deformation of cellular membranes. In this study, we propose a new physical model by which molecular turnover is coupled with three-dimensional membrane deformation to explore mechanosensing roles of turnover in cellular membrane deformations. In particular, as an example of microscopic machinery, based on a coarse-graining description, we suppose that molecular turnover depends on the local membrane strain. Using the proposed model, we demonstrate computational simulations of a single vesicle. The results show that molecular turnover adaptively facilitates vesicle deformation, owing to its stress dependence; while the vesicle drastically expands in the case with low bending rigidity, it shrinks in that with high bending rigidity. Moreover, localized active tension on the membrane causes cellular migration by driving the directional transport of molecules within the cell. These results illustrate the use of the proposed model as well as the role of turnover in the dynamic deformations of cellular membranes.", "classifications": [ { "id": "Okuda", "label": "Group Okuda", "parent": "Imayoshi", "type": "group" }, { "id": "Imayoshi", "label": "Team Imayoshi", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Satoru", "last_name": "Okuda", "name": null }, { "creator_type": "author", "first_name": "Mototsugu", "last_name": "Eiraku", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/s10237-017-0920-8" }, "pmcid": { "normalized": "PMC5599494" }, "pmid": { "normalized": "28555369" } }, "mesh": [ { "descriptor": "Cell Membrane", "descriptor_ui": "D002462", "major_topic": false }, { "descriptor": "Cell Movement", "descriptor_ui": "D002465", "major_topic": false }, { "descriptor": "Computer Simulation", "descriptor_ui": "D003198", "major_topic": false }, { "descriptor": "Imaging, Three-Dimensional", "descriptor_ui": "D021621", "major_topic": true }, { "descriptor": "Membrane Fluidity", "descriptor_ui": "D008560", "major_topic": false }, { "descriptor": "Models, Biological", "descriptor_ui": "D008954", "major_topic": true }, { "descriptor": "Thermodynamics", "descriptor_ui": "D013816", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Oct", "date_precision": "unknown", "issue": "5", "normalized_date": null, "pages": "1805-1818", "proceedings_title": null, "publisher": "", "title": "Biomechanics and modeling in mechanobiology", "volume": "16", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Role of molecular turnover in dynamic deformation of a three-dimensional cellular membrane.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Tenascin-X (TNX), an extracellular matrix protein, is abundantly expressed in peripheral nerves. However, the physiological role of TNX in peripheral nerves remains unknown. In this study, we found that actin levels in sciatic nerves of TNX-deficient mice were markedly decreased. Since actin was highly expressed in endothelial cells in wild-type sciatic nerves, we assessed morphological alterations of blood vessels in TNX-null sciatic nerves. The density of blood vessels was significantly decreased and the size of blood vessels was larger than those in wild-type sciatic nerves. Immunofluorescence showed that TNX was expressed by Schwann cells and fibroblasts in sciatic nerves. The results suggest that TNX secreted from Schwann cells and/or fibroblasts is involved in blood vessel formation in peripheral nerves.", "classifications": [ { "id": "Yokota", "label": "Group Yokota", "parent": "Enomoto", "type": "group" }, { "id": "Enomoto", "label": "Team Enomoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Hiromichi", "last_name": "Sakai", "name": null }, { "creator_type": "author", "first_name": "Shigefumi", "last_name": "Yokota", "name": null }, { "creator_type": "author", "first_name": "Naoyo", "last_name": "Kajitani", "name": null }, { "creator_type": "author", "first_name": "Tsunao", "last_name": "Yoneyama", "name": null }, { "creator_type": "author", "first_name": "Kohei", "last_name": "Kawakami", "name": null }, { "creator_type": "author", "first_name": "Yukihiko", "last_name": "Yasui", "name": null }, { "creator_type": "author", "first_name": "Ken-Ichi", "last_name": "Matsumoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.neures.2017.06.003" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "28668501" } }, "mesh": [ { "descriptor": "Actins", "descriptor_ui": "D000199", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Blood Vessels", "descriptor_ui": "D001808", "major_topic": false }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Schwann Cells", "descriptor_ui": "D012583", "major_topic": false }, { "descriptor": "Sciatic Nerve", "descriptor_ui": "D012584", "major_topic": false }, { "descriptor": "Tenascin", "descriptor_ui": "D019063", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Nov", "date_precision": "unknown", "issue": "", "normalized_date": null, "pages": "1-7", "proceedings_title": null, "publisher": "", "title": "Neuroscience research", "volume": "124", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "A potential contribution of tenascin-X to blood vessel formation in peripheral nerves.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Cardiac arrhythmias have long been regarded as derangement of electrical impulse initiation and conduction within the heart. However, underlying mechanisms for arrhythmogenesis are not fully understood solely from the electrophysiological viewpoint. This review article discusses pathogenesis of arrhythmias from non-electrical aspects, which were elucidated by spatiotemporal imaging of functional molecules in combination with morphological analysis of living heart tissues. Intracellular Ca(2+) ([Ca(2+) ](i) ) overload, caused by myocardial injury, provokes Ca(2+) waves that could lead to abnormal excitations, i.e., triggered arrhythmias. Depressed Ca(2+) release from the sarcoplasmic reticulum, caused by ischemia, heart failure, or T-tubular remodeling, results in spatiotemporally inhomogeneous [Ca(2+) ](i) dynamics that could disturb impulse conduction, leading to reentrant tachyarrhythmias. Impairment of the gap junction-mediated intercellular communications, which provokes derangement of impulse propagation of the myocardium, also leads to reentrant arrhythmias. Interpositions of non-cardiomyocytes, especially fibroblasts, in the myocardium could also contribute to arrhythmogenesis via heterocellular gap-junctional coupling with cardiomyocytes. Furthermore, alterations in myocardial histology, e.g., density and arrangements of myocytes in association with gap-junctional distributions, could constitute important pathologic bases of atrial fibrillation. Integration of these molecular, functional, and morphological features of the myocardium, unveiled by experimental pathological approaches, would pave a new way for understanding pathogenesis of cardiac arrhythmias.", "classifications": [ { "id": "Tanaka", "label": "Group Tanaka", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Hideo", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Taka-Aki", "last_name": "Matsuyama", "name": null }, { "creator_type": "author", "first_name": "Tetsuro", "last_name": "Takamatsu", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/pin.12487" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "27995745" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Arrhythmias, Cardiac", "descriptor_ui": "D001145", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Jan", "date_precision": "unknown", "issue": "1", "normalized_date": null, "pages": "8-16", "proceedings_title": null, "publisher": "", "title": "Pathology international", "volume": "67", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Towards an integrated understanding of cardiac arrhythmogenesis - Growing roles of experimental pathology.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Recently, many types of in vitro 3‐D culture systems have been developed to recapitulate the in vivo growth conditions of cancer. The cancer 3‐D culture methods aim to preserve the biological characteristics of original tumors better than conventional 2‐D monolayer cultures, and include tumor‐derived organoids, tumor‐derived spheroids, organotypic multicellular spheroids, and multicellular tumor spheroids. The 3‐D culture methods differ in terms of cancer cell sources, protocols for cell handling, and the required time intervals. Tumor‐derived spheroids are unique because they are purposed for the enrichment of cancer stem cells (CSCs) or cells with stem cell‐related characteristics. These spheroids are grown as floating spheres and have been used as surrogate systems to evaluate the CSC‐related characteristics of solid tumors in vitro. Because eradication of CSCs is likely to be of clinical importance due to their association with the malignant nature of cancer cells, such as tumorigenicity or chemoresistance, the investigation of tumor‐derived spheroids may provide invaluable clues to fight against cancer. Spheroid cultures have been established from cancers including glioma, breast, colon, ovary, and prostate cancers, and their biological and biochemical characteristics have been investigated by many research groups. In addition to the investigation of CSCs, tumor‐derived spheroids may prove to be instrumental for a high‐throughput screening platform or for the cultivation of CSC‐related tumor cells found in the circulation or body fluids.", "classifications": [ { "id": "Okamoto", "label": "Group Okamoto", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Ishiguro", "name": null }, { "creator_type": "author", "first_name": "Hirokazu", "last_name": "Ohata", "name": null }, { "creator_type": "author", "first_name": "Ai", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Kaoru", "last_name": "Yamawaki", "name": null }, { "creator_type": "author", "first_name": "Takayuki", "last_name": "Enomoto", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Okamoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/cas.13155" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "28064442" } }, "mesh": [ { "descriptor": "Cell Culture Techniques", "descriptor_ui": "D018929", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Neoplasms", "descriptor_ui": "D009369", "major_topic": false }, { "descriptor": "Neoplastic Stem Cells", "descriptor_ui": "D014411", "major_topic": false }, { "descriptor": "Spheroids, Cellular", "descriptor_ui": "D018874", "major_topic": false }, { "descriptor": "Tumor Cells, Cultured", "descriptor_ui": "D014407", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Mar", "date_precision": "unknown", "issue": "3", "normalized_date": null, "pages": "283-289", "proceedings_title": null, "publisher": "", "title": "Cancer Science", "volume": "108", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Tumor‐derived spheroids: Relevance to cancer stem cells and clinical applications.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Rhabdomyosarcoma (RMS) is a soft tissue sarcoma and is most frequently found in children. In RMS, there are two major subtypes, that is, embryonal RMS and alveolar RMS (ARMS). ARMS has exclusively the worse prognosis and is caused by formation of the chimeric PAX3-FOXO1 gene. Regarding cancer, the Warburg effect is known as a feature of cancer-specific metabolism. Polypyrimidine tract-binding protein 1 (PTBP1), a splicer of pyruvate kinase muscle (PKM) mRNA, is a positive regulator of cancer-specific energy metabolism. We investigated the expression and effects of muscle-specific miR-1 and miR-133b on RMS cells (RD, KYM-1, Rh30, and Rh41) from the view of energy metabolism and regulation of the chimeric gene. As a result, downregulated miR-1 and miR-133b/upregulated PTBP1 were found in RMS cell lines as well as in RMS clinical cases. Ectopic expression of either miR in both types of RMS cells induced autophagic cell death through silencing of PTBP1. Interestingly, we validated that miR-133b also knock downed PAX3-FOXO1. Moreover, we found that PAX3-FOXO1 positively regulated the PKM2-dominant expression through enhanced expression of PTBP1. These findings suggest that the miR-1 and miR-133b/PTBP1 axis and miR-133b/PAX3-FOXO1/PTBP1 axis contributed to the maintenance of cancer-specific energy metabolism.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Nobuhiko", "last_name": "Sugito", "name": null }, { "creator_type": "author", "first_name": "Kohei", "last_name": "Taniguchi", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Kuranaga", "name": null }, { "creator_type": "author", "first_name": "Maki", "last_name": "Ohishi", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Yuko", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Mitsuru", "last_name": "Miyachi", "name": null }, { "creator_type": "author", "first_name": "Ken", "last_name": "Kikuchi", "name": null }, { "creator_type": "author", "first_name": "Hajime", "last_name": "Hosoi", "name": null }, { "creator_type": "author", "first_name": "Yukihiro", "last_name": "Akao", "name": null } ], "identifiers": { "doi": { "normalized": "10.1089/nat.2017.0673" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "28981396" } }, "mesh": [ { "descriptor": "Adolescent", "descriptor_ui": "D000293", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Death", "descriptor_ui": "D016923", "major_topic": false }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Child", "descriptor_ui": "D002648", "major_topic": false }, { "descriptor": "Child, Preschool", "descriptor_ui": "D002675", "major_topic": false }, { "descriptor": "Energy Metabolism", "descriptor_ui": "D004734", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Heterogeneous-Nuclear Ribonucleoproteins", "descriptor_ui": "D034441", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Infant", "descriptor_ui": "D007223", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred BALB C", "descriptor_ui": "D008807", "major_topic": false }, { "descriptor": "Mice, Nude", "descriptor_ui": "D008819", "major_topic": false }, { "descriptor": "MicroRNAs", "descriptor_ui": "D035683", "major_topic": false }, { "descriptor": "Oncogene Proteins, Fusion", "descriptor_ui": "D015514", "major_topic": false }, { "descriptor": "Paired Box Transcription Factors", "descriptor_ui": "D051761", "major_topic": false }, { "descriptor": "Polypyrimidine Tract-Binding Protein", "descriptor_ui": "D038941", "major_topic": false }, { "descriptor": "Rhabdomyosarcoma, Alveolar", "descriptor_ui": "D018232", "major_topic": false }, { "descriptor": "Rhabdomyosarcoma, Embryonal", "descriptor_ui": "D018233", "major_topic": false }, { "descriptor": "Xenograft Model Antitumor Assays", "descriptor_ui": "D023041", "major_topic": false }, { "descriptor": "Young Adult", "descriptor_ui": "D055815", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Dec", "date_precision": "unknown", "issue": "6", "normalized_date": null, "pages": "365-377", "proceedings_title": null, "publisher": "", "title": "Nucleic acid therapeutics", "volume": "27", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Cancer-Specific Energy Metabolism in Rhabdomyosarcoma Cells Is Regulated by MicroRNA.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Protoporphyrin IX (PpIX), a biochemical converted from 5-aminolevulinc acid (5-ALA) in living cells, is useful for intraoperative fluorescent detection of cancer metastasis in lymph nodes (LNs). However, unknown is whether the fluorescence of PpIX can be detected in the LNs when they coexist with indigo carmine, a blue dye commonly used for identification of sentinel LNs during surgery. To address this issue, we sought to evaluate the diagnostic usefulness of PpIX fluorescence in the presence of indigo carmine in a mouse LN metastasis model of rectal cancer after administration of 5-ALA. Spectral analysis of pure chemicals revealed that the absorption spectrum of indigo carmine widely overlapped with the fluorescence spectrum of PpIX specifically at the peak of 632nm, a common emission wavelength for detecting PpIX, but not at the other peak of 700nm. Due to such spectral overlap, the PpIX fluorescence intensity was significantly attenuated by mixture with indigo carmine at 632nm, but not at 700nm. Accordingly, fluorescent measurements of the mouse metastatic LN revealed more intense presentation of PpIX at 700nm than at 632nm, indicating that the diagnostic usefulness is greater at 700nm than at 632nm for the indigo carmine-dyed LNs after administration of 5-ALA. From these observations, we propose that the fluorescence measurement is more efficient at 700nm than at 632nm for detection of PpIX in metastatic LNs stained with indigo carmine.", "classifications": [ { "id": "Tanaka", "label": "Group Tanaka", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Hisataka", "last_name": "Matsuo", "name": null }, { "creator_type": "author", "first_name": "Yoshinori", "last_name": "Harada", "name": null }, { "creator_type": "author", "first_name": "Takeo", "last_name": "Minamikawa", "name": null }, { "creator_type": "author", "first_name": "Yoshiyuki", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Yasutoshi", "last_name": "Murayama", "name": null }, { "creator_type": "author", "first_name": "Eigo", "last_name": "Otsuji", "name": null }, { "creator_type": "author", "first_name": "Tetsuro", "last_name": "Takamatsu", "name": null }, { "creator_type": "author", "first_name": "Hideo", "last_name": "Tanaka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.pdpdt.2017.05.019" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "28578125" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Colorectal Neoplasms", "descriptor_ui": "D015179", "major_topic": false }, { "descriptor": "Coloring Agents", "descriptor_ui": "D004396", "major_topic": false }, { "descriptor": "Indigo Carmine", "descriptor_ui": "D007203", "major_topic": false }, { "descriptor": "Lymph Nodes", "descriptor_ui": "D008198", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Neoplasm Metastasis", "descriptor_ui": "D009362", "major_topic": false }, { "descriptor": "Optical Imaging", "descriptor_ui": "D061848", "major_topic": false }, { "descriptor": "Protoporphyrins", "descriptor_ui": "D011524", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Sep", "date_precision": "unknown", "issue": "", "normalized_date": null, "pages": "175-180", "proceedings_title": null, "publisher": "", "title": "Photodiagnosis and photodynamic therapy", "volume": "19", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Efficient fluorescence detection of protoporphyrin IX in metastatic lymph nodes of murine colorectal cancer stained with indigo carmine.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Purinergic signaling, mediated mainly by G protein-coupled P2Y receptors (P2YRs), is now attracting attention as a new therapeutic target for preventing or treating cardiovascular diseases. Observations using mice with genetically modified P2YRs and/or treated with a pharmacological P2YR inhibitor have helped us understand the physiological and pathological significance of P2YRs in the cardiovascular system. P2YR-mediated biological functions are predominantly activated by mononucleotides released from non-adrenergic, non-cholinergic nerve endings or non-secretory tissues in response to physical stress or cell injury, though recent studies have suggested the occurrence of ligand-independent P2YR function through receptor-receptor interactions (oligomerization) in several biological processes. In this review, we introduce the functions of P2YRs and possible dimerization with G protein-coupled receptors (GPCRs) in the cardiovascular system. We focus especially on the crosstalk between uridine nucleotide-responsive P2Y(6)R and angiotensin (Ang) II type1 receptor (AT1R) signaling, and introduce our recent finding that the P2Y(6)R antagonist MRS2578 interrupts heterodimerization between P2Y(6)R and AT1R, thereby reducing the risk of AT1R-stimulated hypertension in mice. These results strongly suggest that targeting P2Y(6)R oligomerization could be an effective new strategy to reduce the risk of cardiovascular diseases.", "classifications": [ { "id": "Nishida", "label": "Group Nishida", "parent": "Nishida", "type": "group" }, { "id": "Nishimura", "label": "Group Nishimura", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Akiyuki", "last_name": "Nishimura", "name": null }, { "creator_type": "author", "first_name": "Caroline", "last_name": "Sunggip", "name": null }, { "creator_type": "author", "first_name": "Sayaka", "last_name": "Oda", "name": null }, { "creator_type": "author", "first_name": "Takuro", "last_name": "Numaga-Tomita", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Tsuda", "name": null }, { "creator_type": "author", "first_name": "Motohiro", "last_name": "Nishida", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.pharmthera.2017.06.010" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "28648830" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cardiovascular Diseases", "descriptor_ui": "D002318", "major_topic": false }, { "descriptor": "Homeostasis", "descriptor_ui": "D006706", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Myocardium", "descriptor_ui": "D009206", "major_topic": false }, { "descriptor": "Receptors, Purinergic P2Y", "descriptor_ui": "D058470", "major_topic": false }, { "descriptor": "Risk Factors", "descriptor_ui": "D012307", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Dec", "date_precision": "unknown", "issue": "", "normalized_date": null, "pages": "113-128", "proceedings_title": null, "publisher": "", "title": "Pharmacology & therapeutics", "volume": "180", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Purinergic P2Y receptors: Molecular diversity and implications for treatment of cardiovascular diseases.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Stepwise differentiation of epidermal cells is essential for development of stratified epithelium, but the underlying mechanisms remain unclear. Here, we show that Tbx3, a member of the T-box family of transcription factors, plays a pivotal role in this mechanism. Tbx3 is expressed in both basal and suprabasal cells in the interfollicular epidermis of mouse embryos. Epidermis-specific Tbx3 conditional knockout (cKO) embryos are small in size and display a thinner epidermis with an impaired barrier function. In the Tbx3 cKO epidermis, keratin 5-positive undifferentiated cells, which reside in both basal and suprabasal layers of wild-type embryos, are localized exclusively in the basal layer. In addition, mRNA expression levels of granular cell markers are increased in the Tbx3 cKO epidermis, suggesting that Tbx3 prevents premature differentiation of spinous cells. We further show that Tbx3 maintains the proliferative potential of basal cells and ensures their planar-oriented cell division. Moreover, Tbx3 is shown to be required for the expression of Hes1, a well-known Notch signaling target protein that is essential for epidermal development. We therefore propose that Tbx3 functions upstream of Hes1 to regulate proliferation and differentiation of basal and suprabasal cells during epidermal development.", "classifications": [ { "id": "Toyoshima", "label": "Group Toyoshima", "parent": "Toyoshima", "type": "group" }, { "id": "Toyoshima", "label": "Team Toyoshima", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Ryo", "last_name": "Ichijo", "name": null }, { "creator_type": "author", "first_name": "Yui", "last_name": "Iizuka", "name": null }, { "creator_type": "author", "first_name": "Hirokazu", "last_name": "Kubo", "name": null }, { "creator_type": "author", "first_name": "Fumiko", "last_name": "Toyoshima", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/gtc.12476" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "28205312" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Epidermal Cells", "descriptor_ui": "D000078404", "major_topic": false }, { "descriptor": "Epidermis", "descriptor_ui": "D004817", "major_topic": false }, { "descriptor": "Gene Expression", "descriptor_ui": "D015870", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "T-Box Domain Proteins", "descriptor_ui": "D020825", "major_topic": false }, { "descriptor": "Transcription Factor HES-1", "descriptor_ui": "D000072056", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Mar", "date_precision": "unknown", "issue": "3", "normalized_date": null, "pages": "284-292", "proceedings_title": null, "publisher": "", "title": "Genes to cells : devoted to molecular & cellular mechanisms", "volume": "22", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Essential roles of Tbx3 in embryonic skin development during epidermal stratification.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "We investigate a two-dimensional spatially extended system that has a weak sense of excitability, where an excitation wave has a uniform profile and propagates only within a finite range. Using a cellular automaton model of such a weakly excitable system, we show that three kinds of sustained dynamics emerge when nonlocal spatial interactions are provided, where a chain of local wave propagation and nonlocal activation forms an elementary oscillatory cycle. Transition between different oscillation regimes can be understood as different ways of interactions among these cycles. Analytical expressions are given for the oscillation probability near the onset of oscillations.", "classifications": [ { "id": "Nagayama", "label": "Group Nagayama", "parent": "Fujiwara", "type": "group" }, { "id": "Fujiwara", "label": "Team Fujiwara", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yasuaki", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Kitahata", "name": null }, { "creator_type": "author", "first_name": "Masaharu", "last_name": "Nagayama", "name": null } ], "identifiers": { "doi": { "normalized": "10.1103/physreve.96.022213" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "28950600" } }, "mesh": [], "publication": { "conference_name": null, "date": "2017 Aug", "date_precision": "unknown", "issue": "2-1", "normalized_date": null, "pages": "022213", "proceedings_title": null, "publisher": "", "title": "Physical review. E", "volume": "96", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Sustained dynamics of a weakly excitable system with nonlocal interactions.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "OBJECTIVE: A recent study identified a survival benefit with prophylactic neck dissection (ND) at the time of primary surgery as compared with watchful waiting followed by therapeutic neck dissection for nodal relapse, in patients with cN0 oral squamous cell carcinoma (OSCC). Alternative management of cN0 neck cancer is recommended to minimize the adverse effects of ND, indicating the need for sentinel node biopsy (SNB) and limited neck dissection. We conducted a multicenter Phase II study to examine the feasibility of SNB for clinically N0 OSCC. METHODS: Previously untreated N0 OSCC patients (n=57) with clinical late-T2 or T3 tumors were enrolled across 10 institutions. SNB navigated with multislice frozen section analysis of sentinel nodes (SNs) and SNB supported sentinel node lymphatic basin dissection (SN basin dissection) were performed in a one-stage procedure. The endpoint was to investigate the rate of false-negative metastases after SN basin dissection and SNB alone. RESULTS: Most tumors were late-T2 lesions (n=50; 87.7%). SNs were identified in all patients. A total of 196 SNs were detected. Among these SNs, 35 (17.8%) were positive for metastasis (9 in level I, 12 in level II, 12 in level III, 1 in level V and 2 in the contralateral region of the neck). The false-negative rate of SNB supported by SN basin dissection and SNB alone was 4.5% and 9.1%, respectively. The concordance of the SN status in intraoperative frozen sections with the permanent histopathology was 97.4% (191/196). The sensitivity and specificity of intraoperative pathological evaluation were 85.7% (30/35) and 100% (30/30), respectively. The 3-year overall survival (OS) and disease-free survival was 89.5% and 82.5%, respectively. The OS of SN-negative patients was significantly longer than that of SN-positive patients (P=0.047). CONCLUSION: The current study verified that SN basin dissection was a useful back-up procedure for SNB performed as a one-stage procedure, showing a low false-negative rate. SNB alone is an appropriate staging method for patients with clinical N0 staging, and a reliable procedure to determine the appropriate levels for neck dissection.", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Kouki", "last_name": "Miura", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Hirakawa", "name": null }, { "creator_type": "author", "first_name": "Hirokazu", "last_name": "Uemura", "name": null }, { "creator_type": "author", "first_name": "Seiichi", "last_name": "Yoshimoto", "name": null }, { "creator_type": "author", "first_name": "Akihiro", "last_name": "Shiotani", "name": null }, { "creator_type": "author", "first_name": "Masashi", "last_name": "Sugasawa", "name": null }, { "creator_type": "author", "first_name": "Akihiro", "last_name": "Homma", "name": null }, { "creator_type": "author", "first_name": "Junkichi", "last_name": "Yokoyama", "name": null }, { "creator_type": "author", "first_name": "Kiyoaki", "last_name": "Tsukahara", "name": null }, { "creator_type": "author", "first_name": "Tomokazu", "last_name": "Yoshizaki", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null }, { "creator_type": "author", "first_name": "Keitaro", "last_name": "Matsuo", "name": null }, { "creator_type": "author", "first_name": "Yasuo", "last_name": "Ohkura", "name": null }, { "creator_type": "author", "first_name": "Shigeru", "last_name": "Kosuda", "name": null }, { "creator_type": "author", "first_name": "Yasuhisa", "last_name": "Hasegawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.anl.2016.07.008" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "27496008" } }, "mesh": [ { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Aged, 80 and over", "descriptor_ui": "D000369", "major_topic": false }, { "descriptor": "Carcinoma, Squamous Cell", "descriptor_ui": "D002294", "major_topic": false }, { "descriptor": "Disease-Free Survival", "descriptor_ui": "D018572", "major_topic": false }, { "descriptor": "False Negative Reactions", "descriptor_ui": "D005188", "major_topic": false }, { "descriptor": "Feasibility Studies", "descriptor_ui": "D005240", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Frozen Sections", "descriptor_ui": "D005629", "major_topic": false }, { "descriptor": "Head and Neck Neoplasms", "descriptor_ui": "D006258", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Mouth Neoplasms", "descriptor_ui": "D009062", "major_topic": false }, { "descriptor": "Neck Dissection", "descriptor_ui": "D037981", "major_topic": false }, { "descriptor": "Neoplasm Staging", "descriptor_ui": "D009367", "major_topic": false }, { "descriptor": "Otorhinolaryngologic Surgical Procedures", "descriptor_ui": "D013517", "major_topic": false }, { "descriptor": "Prospective Studies", "descriptor_ui": "D011446", "major_topic": false }, { "descriptor": "Radiotherapy, Adjuvant", "descriptor_ui": "D018714", "major_topic": false }, { "descriptor": "Sentinel Lymph Node Biopsy", "descriptor_ui": "D021701", "major_topic": false }, { "descriptor": "Squamous Cell Carcinoma of Head and Neck", "descriptor_ui": "D000077195", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Jun", "date_precision": "unknown", "issue": "3", "normalized_date": null, "pages": "319-326", "proceedings_title": null, "publisher": "", "title": "Auris, nasus, larynx", "volume": "44", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Sentinel node biopsy for oral cancer: A prospective multicenter Phase II trial.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Sex-determining region Y-box 2 (SOX2) is an essential factor involved in the self-renewal and pluripotency of embryonic stem cells and has functions in cell survival and progression in many types of cancers. Here, we found that several endometrial cancer cell lines expressed SOX2, which was required for cell growth. Additionally, SOX2 overexpression regulated the expression of cyclin-dependent kinase inhibitor 1A (CDKN1A), and SOX2 specifically bound to p21 promoter DNA in endometrial cancer cell lines expressing SOX2. Expressions of SOX2 in endometrial cancer patients were significantly correlated with histological grade and poor prognosis. Moreover, low p21 together with high SOX2 expressions in advanced endometrial cancer patients were associated with the most unfavorable outcomes of patients. These results indicated that simultaneous measurement of SOX2 and p21 expression in endometrial cancer patients may be a useful biomarker for patient prognosis.", "classifications": [ { "id": "Okamoto", "label": "Group Okamoto", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Kaoru", "last_name": "Yamawaki", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Ishiguro", "name": null }, { "creator_type": "author", "first_name": "Yutaro", "last_name": "Mori", "name": null }, { "creator_type": "author", "first_name": "Kosuke", "last_name": "Yoshihara", "name": null }, { "creator_type": "author", "first_name": "Kazuaki", "last_name": "Suda", "name": null }, { "creator_type": "author", "first_name": "Ryo", "last_name": "Tamura", "name": null }, { "creator_type": "author", "first_name": "Masayuki", "last_name": "Yamaguchi", "name": null }, { "creator_type": "author", "first_name": "Masayuki", "last_name": "Sekine", "name": null }, { "creator_type": "author", "first_name": "Katsunori", "last_name": "Kashima", "name": null }, { "creator_type": "author", "first_name": "Masaya", "last_name": "Higuchi", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Fujii", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Okamoto", "name": null }, { "creator_type": "author", "first_name": "Takayuki", "last_name": "Enomoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/cas.13196" }, "pmcid": { "normalized": "PMC5406528" }, "pmid": { "normalized": "28188685" } }, "mesh": [ { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Aged, 80 and over", "descriptor_ui": "D000369", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Blotting, Western", "descriptor_ui": "D015153", "major_topic": false }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Cyclin-Dependent Kinase Inhibitor p21", "descriptor_ui": "D050759", "major_topic": false }, { "descriptor": "Endometrial Neoplasms", "descriptor_ui": "D016889", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Gene Expression Regulation, Neoplastic", "descriptor_ui": "D015972", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Immunohistochemistry", "descriptor_ui": "D007150", "major_topic": false }, { "descriptor": "Kaplan-Meier Estimate", "descriptor_ui": "D053208", "major_topic": false }, { "descriptor": "Mice, Inbred NOD", "descriptor_ui": "D016688", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Mice, SCID", "descriptor_ui": "D016513", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Prognosis", "descriptor_ui": "D011379", "major_topic": false }, { "descriptor": "Reverse Transcriptase Polymerase Chain Reaction", "descriptor_ui": "D020133", "major_topic": false }, { "descriptor": "RNA Interference", "descriptor_ui": "D034622", "major_topic": false }, { "descriptor": "SOXB1 Transcription Factors", "descriptor_ui": "D055748", "major_topic": false }, { "descriptor": "Transplantation, Heterologous", "descriptor_ui": "D014183", "major_topic": false }, { "descriptor": "Tumor Suppressor Protein p53", "descriptor_ui": "D016159", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Apr", "date_precision": "unknown", "issue": "4", "normalized_date": null, "pages": "632-640", "proceedings_title": null, "publisher": "", "title": "Cancer science", "volume": "108", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Sox2-dependent inhibition of p21 is associated with poor prognosis of endometrial cancer.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Parasite infections cause dramatic anatomical and ultrastructural changes in host plants. Cyst nematodes are parasites that invade host roots and induce a specific feeding structure called a syncytium. A syncytium is a large multinucleate cell formed by cell wall dissolution-mediated cell fusion. The soybean cyst nematode (SCN), Heterodera glycines, is a major soybean pathogen. To investigate SCN infection and the syncytium structure, we established an in planta deep imaging system using a clearing solution ClearSee and two-photon excitation microscopy (2PEM). Using this system, we found that several cells were incorporated into the syncytium; the nuclei increased in size and the cell wall openings began to be visible at 2 days after inoculation (DAI). Moreover, at 14 DAI, in the syncytium developed in the cortex, there were thickened concave cell wall pillars that resembled \"Parthenon pillars.\" In contrast, there were many thick board-like cell walls and rarely Parthenon pillars in the syncytium developed in the stele. We revealed that the syncytia were classified into two types based on the pattern of the cell wall structures, which appeared to be determined by the position of the syncytium inside roots. Our results provide new insights into the developmental process of syncytium induced by cyst nematode and a better understanding of the three-dimensional structure of the syncytium in host roots.", "classifications": [ { "id": "Sato", "label": "Group Sato", "parent": "Tsuchiya", "type": "group" }, { "id": "Tsuchiya", "label": "Team Tsuchiya", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Mina", "last_name": "Ohtsu", "name": null }, { "creator_type": "author", "first_name": "Yoshikatsu", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Kurihara", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Suzaki", "name": null }, { "creator_type": "author", "first_name": "Masayoshi", "last_name": "Kawaguchi", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Maruyama", "name": null }, { "creator_type": "author", "first_name": "Tetsuya", "last_name": "Higashiyama", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/s00709-017-1105-0" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "28343256" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Wall", "descriptor_ui": "D002473", "major_topic": false }, { "descriptor": "Giant Cells", "descriptor_ui": "D015726", "major_topic": false }, { "descriptor": "Glycine max", "descriptor_ui": "D013025", "major_topic": false }, { "descriptor": "Microscopy, Fluorescence", "descriptor_ui": "D008856", "major_topic": false }, { "descriptor": "Plant Roots", "descriptor_ui": "D018517", "major_topic": false }, { "descriptor": "Spatio-Temporal Analysis", "descriptor_ui": "D062211", "major_topic": false }, { "descriptor": "Tylenchoidea", "descriptor_ui": "D014431", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Nov", "date_precision": "unknown", "issue": "6", "normalized_date": null, "pages": "2107-2115", "proceedings_title": null, "publisher": "", "title": "Protoplasma", "volume": "254", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Spatiotemporal deep imaging of syncytium induced by the soybean cyst nematode Heterodera glycines.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Recent advances in single-cell time-lapse microscopy have revealed non-genetic heterogeneity and temporal fluctuations of cellular phenotypes. While different phenotypic traits such as abundance of growth-related proteins in single cells may have differential effects on the reproductive success of cells, rigorous experimental quantification of this process has remained elusive due to the complexity of single cell physiology within the context of a proliferating population. We introduce and apply a practical empirical method to quantify the fitness landscapes of arbitrary phenotypic traits, using genealogical data in the form of population lineage trees which can include phenotypic data of various kinds. Our inference methodology for fitness landscapes determines how reproductivity is correlated to cellular phenotypes, and provides a natural generalization of bulk growth rate measures for single-cell histories. Using this technique, we quantify the strength of selection acting on different cellular phenotypic traits within populations, which allows us to determine whether a change in population growth is caused by individual cells' response, selection within a population, or by a mixture of these two processes. By applying these methods to single-cell time-lapse data of growing bacterial populations that express a resistance-conferring protein under antibiotic stress, we show how the distributions, fitness landscapes, and selection strength of single-cell phenotypes are affected by the drug. Our work provides a unified and practical framework for quantitative measurements of fitness landscapes and selection strength for any statistical quantities definable on lineages, and thus elucidates the adaptive significance of phenotypic states in time series data. The method is applicable in diverse fields, from single cell biology to stem cell differentiation and viral evolution.", "classifications": [ { "id": "Wakamoto", "label": "Group Wakamoto", "parent": "Wakamoto", "type": "group" }, { "id": "Wakamoto", "label": "Team Wakamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Takashi", "last_name": "Nozoe", "name": null }, { "creator_type": "author", "first_name": "Edo", "last_name": "Kussell", "name": null }, { "creator_type": "author", "first_name": "Yuichi", "last_name": "Wakamoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1371/journal.pgen.1006653" }, "pmcid": { "normalized": "PMC5360348" }, "pmid": { "normalized": "28267748" } }, "mesh": [ { "descriptor": "Biological Evolution", "descriptor_ui": "D005075", "major_topic": true }, { "descriptor": "Cell Cycle", "descriptor_ui": "D002453", "major_topic": false }, { "descriptor": "Cell Lineage", "descriptor_ui": "D019070", "major_topic": false }, { "descriptor": "Computer Simulation", "descriptor_ui": "D003198", "major_topic": false }, { "descriptor": "Environment", "descriptor_ui": "D004777", "major_topic": false }, { "descriptor": "Escherichia coli", "descriptor_ui": "D004926", "major_topic": false }, { "descriptor": "Genetic Fitness", "descriptor_ui": "D056084", "major_topic": true }, { "descriptor": "Microscopy", "descriptor_ui": "D008853", "major_topic": false }, { "descriptor": "Phenotype", "descriptor_ui": "D010641", "major_topic": false }, { "descriptor": "Probability", "descriptor_ui": "D011336", "major_topic": false }, { "descriptor": "Selection, Genetic", "descriptor_ui": "D012641", "major_topic": true }, { "descriptor": "Single-Cell Analysis", "descriptor_ui": "D059010", "major_topic": true }, { "descriptor": "Stochastic Processes", "descriptor_ui": "D013269", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Mar", "date_precision": "unknown", "issue": "3", "normalized_date": null, "pages": "e1006653", "proceedings_title": null, "publisher": "", "title": "PLoS genetics", "volume": "13", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Inferring fitness landscapes and selection on phenotypic states from single-cell genealogical data.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Most biological processes accelerate with temperature, for example cell division. In contrast, the circadian rhythm period is robust to temperature fluctuation, termed temperature compensation. Temperature compensation is peculiar because a system-level property (i.e., the circadian period) is stable under varying temperature while individual components of the system (i.e., biochemical reactions) are usually temperature-sensitive. To understand the mechanism for period stability, we measured the time series of circadian clock transcripts in cultured C6 glioma cells. The amplitudes of Cry1 and Dbp circadian expression increased significantly with temperature. In contrast, other clock transcripts demonstrated no significant change in amplitude. To understand these experimental results, we analyzed mathematical models with different network topologies. It was found that the geometric mean amplitude of gene expression must increase to maintain a stable period with increasing temperatures and reaction speeds for all models studied. To investigate the generality of this temperature-amplitude coupling mechanism for period stability, we revisited data on the yeast metabolic cycle (YMC) period, which is also stable under temperature variation. We confirmed that the YMC amplitude increased at higher temperatures, suggesting temperature-amplitude coupling as a common mechanism shared by circadian and 4 h-metabolic rhythms.", "classifications": [ { "id": "Mochizuki", "label": "Group Mochizuki", "parent": "Eiraku", "type": "group" }, { "id": "Eiraku", "label": "Team Eiraku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Gen", "last_name": "Kurosawa", "name": null }, { "creator_type": "author", "first_name": "Atsuko", "last_name": "Fujioka", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Koinuma", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Mochizuki", "name": null }, { "creator_type": "author", "first_name": "Yasufumi", "last_name": "Shigeyoshi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1371/journal.pcbi.1005501" }, "pmcid": { "normalized": "PMC5464531" }, "pmid": { "normalized": "28594845" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Computational Biology", "descriptor_ui": "D019295", "major_topic": false }, { "descriptor": "Models, Biological", "descriptor_ui": "D008954", "major_topic": true }, { "descriptor": "Periodicity", "descriptor_ui": "D010507", "major_topic": true }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Temperature", "descriptor_ui": "D013696", "major_topic": true } ], "publication": { "conference_name": null, "date": "2017 Jun", "date_precision": "unknown", "issue": "6", "normalized_date": null, "pages": "e1005501", "proceedings_title": null, "publisher": "", "title": "PLoS computational biology", "volume": "13", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Temperature-amplitude coupling for stable biological rhythms at different temperatures.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Aging has a remarkable effect on cardiovascular homeostasis and it is known as the major non-modifiable risk factor in the development of hypertension. Medications targeting sympathetic nerve system and/or renin-angiotensin-aldosterone system are widely accepted as a powerful therapeutic strategy to improve hypertension, although the control rates remain unsatisfactory especially in the elder patients with hypertension. Purinergic receptors, activated by adenine, uridine nucleotides and nucleotide sugars, play pivotal roles in many biological processes, including platelet aggregation, neurotransmission and hormone release, and regulation of cardiovascular contractility. Since clopidogrel, a selective inhibitor of G protein-coupled purinergic P2Y(12) receptor (P2Y(12)R), achieved clinical success as an anti-platelet drug, P2YRs has been attracted more attention as new therapeutic targets of cardiovascular diseases. We have revealed that UDP-responsive P2Y(6)R promoted angiotensin type 1 receptor (AT1R)-stimulated vascular remodeling in mice, in an age-dependent manner. Moreover, the age-related formation of heterodimer between AT1R and P2Y(6)R was disrupted by MRS2578, a P2Y(6)R-selective inhibitor. These findings suggest that P2Y(6)R is a therapeutic target to prevent age-related hypertension.", "classifications": [ { "id": "Nishida", "label": "Group Nishida", "parent": "Nishida", "type": "group" }, { "id": "Nishimura", "label": "Group Nishimura", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Caroline", "last_name": "Sunggip", "name": null }, { "creator_type": "author", "first_name": "Akiyuki", "last_name": "Nishimura", "name": null }, { "creator_type": "author", "first_name": "Kakeru", "last_name": "Shimoda", "name": null }, { "creator_type": "author", "first_name": "Takuro", "last_name": "Numaga-Tomita", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Tsuda", "name": null }, { "creator_type": "author", "first_name": "Motohiro", "last_name": "Nishida", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.phrs.2017.03.013" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "28336370" } }, "mesh": [ { "descriptor": "Aging", "descriptor_ui": "D000375", "major_topic": false }, { "descriptor": "Angiotensin II", "descriptor_ui": "D000804", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Antihypertensive Agents", "descriptor_ui": "D000959", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Hypertension", "descriptor_ui": "D006973", "major_topic": false }, { "descriptor": "Isothiocyanates", "descriptor_ui": "D017879", "major_topic": false }, { "descriptor": "Molecular Targeted Therapy", "descriptor_ui": "D058990", "major_topic": true }, { "descriptor": "Purinergic P2 Receptor Antagonists", "descriptor_ui": "D058919", "major_topic": false }, { "descriptor": "Reactive Oxygen Species", "descriptor_ui": "D017382", "major_topic": false }, { "descriptor": "Receptor, Angiotensin, Type 1", "descriptor_ui": "D044140", "major_topic": false }, { "descriptor": "Receptors, Purinergic P2", "descriptor_ui": "D018048", "major_topic": false }, { "descriptor": "Thiourea", "descriptor_ui": "D013890", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Jun", "date_precision": "unknown", "issue": "", "normalized_date": null, "pages": "51-59", "proceedings_title": null, "publisher": "", "title": "Pharmacological research", "volume": "120", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Purinergic P2Y(6) receptors: A new therapeutic target of age-dependent hypertension.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The Activin/Nodal/TGF-beta signaling pathway plays a major role in maintaining mouse epiblast stem cells (EpiSCs). The EpiSC-maintaining medium, which contains Activin A and bFGF, induces differentiation of mouse embryonic stem cells (ESCs) to EpiSCs. Here, we show that Activin A also has an ability to efficiently propagate ESCs without differentiation to EpiSCs when combined with a MEK inhibitor PD0325901. ESCs cultured in Activin+PD retained high-level expression of naive pluripotency-related transcription factors. Genomewide analysis showed that the gene expression profile of ESCs cultured in Activin+PD resembles that of ESCs cultured in 2i. ESCs cultured in Activin+PD also showed features common to the naive pluripotency of ESCs, including the preferential usage of the Oct4 distal enhancer and the self-renewal response to Wnt pathway activation. Our finding shows a role of Activin/Nodal/TGF-beta signaling in stabilizing self-renewal gene regulatory networks in ESCs.", "classifications": [ { "id": "Yamamoto", "label": "Group Yamamoto", "parent": "Toyoshima", "type": "group" }, { "id": "Toyoshima", "label": "Team Toyoshima", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yuhei", "last_name": "Ashida", "name": null }, { "creator_type": "author", "first_name": "May", "last_name": "Nakajima-Koyama", "name": null }, { "creator_type": "author", "first_name": "Akira", "last_name": "Hirota", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Eisuke", "last_name": "Nishida", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/gtc.12467" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "28097777" } }, "mesh": [ { "descriptor": "Activins", "descriptor_ui": "D028341", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Cell Proliferation", "descriptor_ui": "D049109", "major_topic": false }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Germ Layers", "descriptor_ui": "D005855", "major_topic": false }, { "descriptor": "HEK293 Cells", "descriptor_ui": "D057809", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "MAP Kinase Signaling System", "descriptor_ui": "D020935", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mitogen-Activated Protein Kinase 1", "descriptor_ui": "D019950", "major_topic": false }, { "descriptor": "Mitogen-Activated Protein Kinase Kinases", "descriptor_ui": "D020929", "major_topic": false }, { "descriptor": "Mouse Embryonic Stem Cells", "descriptor_ui": "D000066450", "major_topic": false }, { "descriptor": "Pluripotent Stem Cells", "descriptor_ui": "D039904", "major_topic": false }, { "descriptor": "Transcription Factors", "descriptor_ui": "D014157", "major_topic": false }, { "descriptor": "Transforming Growth Factor beta", "descriptor_ui": "D016212", "major_topic": false }, { "descriptor": "Wnt Signaling Pathway", "descriptor_ui": "D060449", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Feb", "date_precision": "unknown", "issue": "2", "normalized_date": null, "pages": "189-202", "proceedings_title": null, "publisher": "", "title": "Genes to cells : devoted to molecular & cellular mechanisms", "volume": "22", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Activin A in combination with ERK1/2 MAPK pathway inhibition sustains propagation of mouse embryonic stem cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "In living cells, biochemical reactions are catalyzed by specific enzymes and connect to one another by sharing substrates and products, forming complex networks. In our previous studies, we established a framework determining the responses to enzyme perturbations only from network topology, and then proved a theorem, called the law of localization, explaining response patterns in terms of network topology. In this paper, we generalize these results to reaction networks with conserved concentrations, which allows us to study any reaction system. We also propose network characteristics quantifying robustness. We compare E. coli metabolic network with randomly rewired networks, and find that the robustness of the E. coli network is significantly higher than that of the random networks.", "classifications": [ { "id": "Mochizuki", "label": "Group Mochizuki", "parent": "Eiraku", "type": "group" }, { "id": "Eiraku", "label": "Team Eiraku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Takashi", "last_name": "Okada", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Mochizuki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1103/physreve.96.022322" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "28950505" } }, "mesh": [ { "descriptor": "Escherichia coli", "descriptor_ui": "D004926", "major_topic": false }, { "descriptor": "Extracellular Signal-Regulated MAP Kinases", "descriptor_ui": "D048049", "major_topic": false }, { "descriptor": "Models, Biological", "descriptor_ui": "D008954", "major_topic": true }, { "descriptor": "Models, Chemical", "descriptor_ui": "D008956", "major_topic": false }, { "descriptor": "Models, Molecular", "descriptor_ui": "D008958", "major_topic": true }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Aug", "date_precision": "unknown", "issue": "2-1", "normalized_date": null, "pages": "022322", "proceedings_title": null, "publisher": "", "title": "Physical review. E", "volume": "96", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Sensitivity and network topology in chemical reaction systems.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Young coconut (Cocos nucifera Linn.) juice (YCJ) has traditionally been consumed to alleviate symptoms associated with the menopause. Recently, the authors demonstrated that short-term (6-week) YCJ supplementation to ovariectomized rats resulted in increased bone mass and bone formation parameter, suggesting that YCJ consumption has a positive effect on bone metabolism and may represent an intervention to help slow the bone loss during menopause transition. The present study sought to determine how long-term (12-week) YCJ supplementation affects bone metabolism in ovariectomized rats, to investigate whether such supplementation may be helpful to in osteoporosis treatment. Ten-week-old female Wistar rats were subjected to either a sham operation (Sham) or bilateral ovariectomy (Ovx). The Ovx+YCJ group received 5X-concentrated YCJ at a dose of 15 ml/kg/day for 12 weeks. Rats in the Ovx group had significantly lower femur bone mineral density than those in the Sham group. YCJ supplementation did not significantly affect this difference. However, YCJ prevented the increase in bone area of the mid third of the femur, a site high in cortical bone, and body weight gain observed following Ovx. Our findings indicate that long-term YCJ intake does not alter bone loss, but rather alleviates body weight gain following menopause.", "classifications": [ { "id": "Suzuki", "label": "Group Suzuki", "parent": "Takekawa", "type": "group" }, { "id": "Takekawa", "label": "Team Takekawa", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Matsushita", "name": null }, { "creator_type": "author", "first_name": "Akira", "last_name": "Minami", "name": null }, { "creator_type": "author", "first_name": "Hiroaki", "last_name": "Kanazawa", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Sanan", "last_name": "Subhadhirasakul", "name": null }, { "creator_type": "author", "first_name": "Kazushi", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Akihiko", "last_name": "Wakatsuki", "name": null } ], "identifiers": { "doi": { "normalized": "10.3892/br.2017.883" }, "pmcid": { "normalized": "PMC5431439" }, "pmid": { "normalized": "28529739" } }, "mesh": [], "publication": { "conference_name": null, "date": "2017 May", "date_precision": "unknown", "issue": "5", "normalized_date": null, "pages": "585-591", "proceedings_title": null, "publisher": "", "title": "Biomedical reports", "volume": "6", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Long-term supplementation with young coconut juice does not prevent bone loss but rather alleviates body weight gain in ovariectomized rats.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Specific interactions between receptors and their target ligands in the presence of nontarget ligands are crucial for biological processes such as T cell ligand discrimination. To discriminate between the target and nontarget ligands, cells have to increase specificity to the target ligands by amplifying the small differences in affinity among ligands. In addition, sensitivity to the ligand concentration and quick discrimination are also important to detect low amounts of target ligands and facilitate fast cellular decision making after ligand recognition. In this work we propose a mechanism for nonlinear specificity amplification (ultraspecificity) based on zero-order saturating reactions, which was originally proposed to explain nonlinear sensitivity amplification (ultrasensitivity) to the ligand concentration. In contrast to the previously proposed proofreading mechanisms that amplify the specificity by a multistep reaction, our model can produce an optimal balance of specificity, sensitivity, and quick discrimination. Furthermore, we show that a model for insensitivity to a large number of nontarget ligands can be naturally derived from a model with the zero-order ultraspecificity. The zero-order ultraspecificity, therefore, may provide an alternative way to understand ligand discrimination from the viewpoint of nonlinear properties in biochemical reactions.", "classifications": [ { "id": "Kobayashi", "label": "Group Kobayashi", "parent": "Wakamoto", "type": "group" }, { "id": "Wakamoto", "label": "Team Wakamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Masashi K.", "last_name": "Kajita", "name": null }, { "creator_type": "author", "first_name": "Kazuyuki", "last_name": "Aihara", "name": null }, { "creator_type": "author", "first_name": "Tetsuya J.", "last_name": "Kobayashi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1103/physreve.96.012405" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "29347185" } }, "mesh": [ { "descriptor": "Cells", "descriptor_ui": "D002477", "major_topic": false }, { "descriptor": "Kinetics", "descriptor_ui": "D007700", "major_topic": false }, { "descriptor": "Ligands", "descriptor_ui": "D008024", "major_topic": true }, { "descriptor": "Models, Biological", "descriptor_ui": "D008954", "major_topic": false }, { "descriptor": "Models, Molecular", "descriptor_ui": "D008958", "major_topic": true }, { "descriptor": "Protein Binding", "descriptor_ui": "D011485", "major_topic": true }, { "descriptor": "Proteins", "descriptor_ui": "D011506", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Jul", "date_precision": "unknown", "issue": "1-1", "normalized_date": null, "pages": "012405", "proceedings_title": null, "publisher": "", "title": "Physical review. E", "volume": "96", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Balancing specificity, sensitivity, and speed of ligand discrimination by zero-order ultraspecificity.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND/AIM: Enhancer of zeste homolog 2 (EZH2) is a histone methyltransferase that is deeply involved in the pathogenesis of lung cancer. We evaluated the metabolic characteristics of non-small cell lung cancer (NSCLC) in patients with and without expression of EZH2 using (18)F-fluorodeoxyglucose positron-emission tomography/ computed tomography ((18)F-FDG PET/CT). MATERIALS AND METHODS: The EZH2 protein expression of 268 patients with resected NSCLC, whose preoperative (18)F-FDG PET/CT information was available, was evaluated by immunohistochemistry with clone 6A10 antibody; cases with Allred score >/=3 were considered positive. RESULTS: Maximized standard uptake values in cases of EZH2-positive NSCLC and adenocarcinoma were significantly higher in comparison to EZH2-negative cases (p<0.001, and p<0.001, respectively). The expression of EZH2 in NSCLC and adenocarcinoma was associated with significantly poorer survival. CONCLUSION: In patients with NSCLC and adenocarcinoma, EZH2 positivity was associated with a high uptake of FDG, suggesting that EZH2 might define metabolically malignant lung cancer.", "classifications": [ { "id": "Hamamoto", "label": "Group Hamamoto", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Gouji", "last_name": "Toyokawa", "name": null }, { "creator_type": "author", "first_name": "Kazuki", "last_name": "Takada", "name": null }, { "creator_type": "author", "first_name": "Tatsuro", "last_name": "Okamoto", "name": null }, { "creator_type": "author", "first_name": "Yuka", "last_name": "Kozuma", "name": null }, { "creator_type": "author", "first_name": "Taichi", "last_name": "Matsubara", "name": null }, { "creator_type": "author", "first_name": "Naoki", "last_name": "Haratake", "name": null }, { "creator_type": "author", "first_name": "Takaki", "last_name": "Akamine", "name": null }, { "creator_type": "author", "first_name": "Shinkichi", "last_name": "Takamori", "name": null }, { "creator_type": "author", "first_name": "Masakazu", "last_name": "Katsura", "name": null }, { "creator_type": "author", "first_name": "Fumihiro", "last_name": "Shoji", "name": null }, { "creator_type": "author", "first_name": "Ryuji", "last_name": "Hamamoto", "name": null }, { "creator_type": "author", "first_name": "Yoshinao", "last_name": "Oda", "name": null }, { "creator_type": "author", "first_name": "Yoshihiko", "last_name": "Maehara", "name": null } ], "identifiers": { "doi": { "normalized": "10.21873/anticanres.11461" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "28314309" } }, "mesh": [ { "descriptor": "Adenocarcinoma", "descriptor_ui": "D000230", "major_topic": false }, { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Aged, 80 and over", "descriptor_ui": "D000369", "major_topic": false }, { "descriptor": "Carcinoma, Non-Small-Cell Lung", "descriptor_ui": "D002289", "major_topic": false }, { "descriptor": "Disease-Free Survival", "descriptor_ui": "D018572", "major_topic": false }, { "descriptor": "Enhancer of Zeste Homolog 2 Protein", "descriptor_ui": "D000071221", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Fluorodeoxyglucose F18", "descriptor_ui": "D019788", "major_topic": false }, { "descriptor": "Gene Expression Profiling", "descriptor_ui": "D020869", "major_topic": false }, { "descriptor": "Gene Expression Regulation, Neoplastic", "descriptor_ui": "D015972", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Immunohistochemistry", "descriptor_ui": "D007150", "major_topic": false }, { "descriptor": "Kaplan-Meier Estimate", "descriptor_ui": "D053208", "major_topic": false }, { "descriptor": "Lung Neoplasms", "descriptor_ui": "D008175", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Positron Emission Tomography Computed Tomography", "descriptor_ui": "D000072078", "major_topic": false }, { "descriptor": "ROC Curve", "descriptor_ui": "D012372", "major_topic": false }, { "descriptor": "Treatment Outcome", "descriptor_ui": "D016896", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Mar", "date_precision": "unknown", "issue": "3", "normalized_date": null, "pages": "1393-1401", "proceedings_title": null, "publisher": "", "title": "Anticancer research", "volume": "37", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Elevated Metabolic Activity on (18)F-FDG PET/CT Is Associated with the Expression of EZH2 in Non-small Cell Lung Cancer.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Chronic inflammation, which is often associated with high all-cause and cardiovascular mortality, is prevalent in patients with renal failure; however, the precise mechanisms remain unclear. High-salt intake was reported to induce lymphangiogenesis and autoimmune diseases via osmotic stimuli with accumulation of sodium or chloride. In addition, sodium was recently reported to be stored in the extremities of dialysis patients. We studied the effects and mechanisms of high salt loading on tissue and systemic inflammation in subtotal-nephrectomized mice (5/6Nx) and in cultured cells. Macrophage infiltration in the peritoneal wall (P<0.001), heart (P<0.05) and para-aortic tissues (P<0.001) was significantly higher in 5/6Nx with salt loading (5/6Nx/NaCl) than in 5/6Nx without salt loading (5/6Nx/Water); however, there were no significant differences in blood pressure and renal function between the groups. Tissue interleukin-6, monocyte chemotactic protein-1 (MCP-1), serum- and glucocorticoid-inducible kinase 1 (Sgk1) and tonicity-responsive enhancer binding protein (TonEBP) mRNA were significantly elevated in the peritoneal wall and heart with 5/6Nx/NaCl when compared with 5/6Nx/Water. Sodium was stored in the abdominal wall, exerting high-osmotic conditions. Reversal of salt loading reduced macrophage infiltration associated with decreased TonEBP in 5/6Nx/NaCl. Macrophage infiltration associated with fibrosis induced by salt loading was decreased in the 5/6Nx/NaCl/CC chemokine receptor 2 (CCR2, receptor of MCP-1)-deficient mice when compared with 5/6Nx/NaCl/Wild mice, suggesting that CCR2 is required for macrophage infiltration in 5/6Nx with NaCl loading. In cultured mesothelial cells and cardiomyocytes, culture media with high NaCl concentration induced MCP-1, Sgk1 and TonEBP mRNA, all of which were suppressed by TonEBP siRNA, indicating that both MCP-1 and Sgk1 are downstream of TonEBP. Our study indicates that high NaCl intake induces MCP-1 expression leading to macrophage infiltration via the TonEBP-MCP-1 pathway in 5/6Nx/NaCl mice, and that TonEBP has a central role in inflammation in patients with renal failure taking high salt.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Fumiko", "last_name": "Sakata", "name": null }, { "creator_type": "author", "first_name": "Yasuhiko", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Masashi", "last_name": "Mizuno", "name": null }, { "creator_type": "author", "first_name": "Akiho", "last_name": "Sawai", "name": null }, { "creator_type": "author", "first_name": "Yasuhiro", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Takako", "last_name": "Tomita", "name": null }, { "creator_type": "author", "first_name": "Mitsuhiro", "last_name": "Tawada", "name": null }, { "creator_type": "author", "first_name": "Akio", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Akiyoshi", "last_name": "Hirayama", "name": null }, { "creator_type": "author", "first_name": "Akihiro", "last_name": "Sagara", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Wada", "name": null }, { "creator_type": "author", "first_name": "Shoichi", "last_name": "Maruyama", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Seiichi", "last_name": "Matsuo", "name": null }, { "creator_type": "author", "first_name": "Enyu", "last_name": "Imai", "name": null }, { "creator_type": "author", "first_name": "Yoshifumi", "last_name": "Takei", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/labinvest.2017.4" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "28165470" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "Chemokine CCL2", "descriptor_ui": "D018932", "major_topic": false }, { "descriptor": "Cytokines", "descriptor_ui": "D016207", "major_topic": false }, { "descriptor": "Epithelial Cells", "descriptor_ui": "D004847", "major_topic": false }, { "descriptor": "Gene Expression", "descriptor_ui": "D015870", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Immediate-Early Proteins", "descriptor_ui": "D017874", "major_topic": false }, { "descriptor": "Immunohistochemistry", "descriptor_ui": "D007150", "major_topic": false }, { "descriptor": "Inflammation", "descriptor_ui": "D007249", "major_topic": false }, { "descriptor": "Inflammation Mediators", "descriptor_ui": "D018836", "major_topic": false }, { "descriptor": "Interleukin-6", "descriptor_ui": "D015850", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice, 129 Strain", "descriptor_ui": "D057507", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Myocytes, Cardiac", "descriptor_ui": "D032383", "major_topic": false }, { "descriptor": "Nephrectomy", "descriptor_ui": "D009392", "major_topic": true }, { "descriptor": "NFATC Transcription Factors", "descriptor_ui": "D050778", "major_topic": false }, { "descriptor": "Osmoregulation", "descriptor_ui": "D064587", "major_topic": false }, { "descriptor": "Protein Serine-Threonine Kinases", "descriptor_ui": "D017346", "major_topic": false }, { "descriptor": "Reverse Transcriptase Polymerase Chain Reaction", "descriptor_ui": "D020133", "major_topic": false }, { "descriptor": "RNA Interference", "descriptor_ui": "D034622", "major_topic": false }, { "descriptor": "Serum-Glucocorticoid Regulated Kinases", "descriptor_ui": "D000099184", "major_topic": false }, { "descriptor": "Sodium Chloride", "descriptor_ui": "D012965", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Apr", "date_precision": "unknown", "issue": "4", "normalized_date": null, "pages": "432-446", "proceedings_title": null, "publisher": "", "title": "Laboratory investigation; a journal of technical methods and pathology", "volume": "97", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Sodium chloride promotes tissue inflammation via osmotic stimuli in subtotal-nephrectomized mice.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The analysis of pharmaceutical industry data indicates that the major reason for drug candidates failing in late stage clinical development is lack of efficacy, with a high proportion of these due to erroneous hypotheses about target to disease linkage. More than ever, there is a requirement to better understand potential new drug targets and their role in disease biology in order to reduce attrition in drug development. Genome editing technology enables precise modification of individual protein coding genes, as well as noncoding regulatory sequences, enabling the elucidation of functional effects in human disease relevant cellular systems. Areas covered: This article outlines applications of CRISPR genome editing technology in target identification and target validation studies. Expert opinion: Applications of CRISPR technology in target validation studies are in evidence and gaining momentum. Whilst technical challenges remain, we are on the cusp of CRISPR being applied in complex cell systems such as iPS derived differentiated cells and stem cell derived organoids. In the meantime, our experience to date suggests that precise genome editing of putative targets in primary cell systems is possible, offering more human disease relevant systems than conventional cell lines.", "classifications": [ { "id": "Yusa", "label": "Group Yusa", "parent": "Eiraku", "type": "group" }, { "id": "Eiraku", "label": "Team Eiraku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Quinn", "last_name": "Lu", "name": null }, { "creator_type": "author", "first_name": "George P.", "last_name": "Livi", "name": null }, { "creator_type": "author", "first_name": "Sundip", "last_name": "Modha", "name": null }, { "creator_type": "author", "first_name": "Kosuke", "last_name": "Yusa", "name": null }, { "creator_type": "author", "first_name": "Ricardo", "last_name": "Macarron", "name": null }, { "creator_type": "author", "first_name": "David J.", "last_name": "Dow", "name": null } ], "identifiers": { "doi": { "normalized": "10.1080/17460441.2017.1317244" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "28388235" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "Clustered Regularly Interspaced Short Palindromic Repeats", "descriptor_ui": "D064112", "major_topic": false }, { "descriptor": "Drug Design", "descriptor_ui": "D015195", "major_topic": true }, { "descriptor": "Drug Discovery", "descriptor_ui": "D055808", "major_topic": false }, { "descriptor": "Drug Industry", "descriptor_ui": "D004345", "major_topic": false }, { "descriptor": "Gene Editing", "descriptor_ui": "D000072669", "major_topic": false }, { "descriptor": "Genome, Human", "descriptor_ui": "D015894", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Molecular Targeted Therapy", "descriptor_ui": "D058990", "major_topic": false }, { "descriptor": "Treatment Failure", "descriptor_ui": "D017211", "major_topic": false }, { "descriptor": "Validation Studies as Topic", "descriptor_ui": "D054928", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Jun", "date_precision": "unknown", "issue": "6", "normalized_date": null, "pages": "541-552", "proceedings_title": null, "publisher": "", "title": "Expert opinion on drug discovery", "volume": "12", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Applications of CRISPR genome editing technology in drug target identification and validation.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: The aim of this retrospective study was to evaluate the clinical relevance of serum p53 antibody (S-p53Ab) as a biomarker and to investigate whether its diagnostic value could be improved when combined with other biomarkers of gastric cancer (GC). PATIENTS AND METHODS: Serum samples were obtained preoperatively from 208 patients with histologically-confirmed GC, including 126 stage I patients (60.6%). Levels of S-p53Ab were assessed by a commercial laboratory using an anti-p53 detection kit. The cut-off value for S-p53Ab was 1.3 U/ml. RESULTS: S-p53Ab was detected in 16.3% (34 of 208) of patients with GC, including 13.6% (22 of 162) of patients with early-stage GC. The positive rates for S-p53Ab, carbohydrate antigen 19-9 (CA19-9), and carcinoembryonic antigen (CEA) of patients with stage I GC were 10.3% (13/126), 2.4% (3/126), and 8.7% (11/126), respectively. Positivity for S-p53Ab was not associated with CA19-9 or CEA positivity (p=0.098 and 0.053, respectively). The positive rate for a diagnosis of GC increased from 16.3% to 29.3% when S-p53-Ab was combined with CEA in this study. We found no significant correlation between the presence of S-p53Ab in GC and overall survival. Conversely, Cox regression analysis revealed that a high level of CA19-9 was an independent prognostic factor for GC in this series (hazard ratio(HR)=3.864; 95% confidence interval(CI)= 1.248-11.959; p=0.019). Kaplan-Meier analyses demonstrated significant differences in survival between patients with elevated levels of both S-p53Ab and CEA and those with elevated levels of only one or neither. CONCLUSION: The diagnostic rate of S-p53Ab was better than that of CA19-9 and CEA in patients with stage I GC. Combined detection of S-p53Ab and CEA may improve the diagnostic sensitivity and may permit more accurate stratification of GC patients.", "classifications": [ { "id": "Hamamoto", "label": "Group Hamamoto", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Masaki", "last_name": "Kunizaki", "name": null }, { "creator_type": "author", "first_name": "Akiko", "last_name": "Fukuda", "name": null }, { "creator_type": "author", "first_name": "Kouki", "last_name": "Wakata", "name": null }, { "creator_type": "author", "first_name": "Tetsuro", "last_name": "Tominaga", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Nonaka", "name": null }, { "creator_type": "author", "first_name": "Takuro", "last_name": "Miyazaki", "name": null }, { "creator_type": "author", "first_name": "Keitaro", "last_name": "Matsumoto", "name": null }, { "creator_type": "author", "first_name": "Yorihisa", "last_name": "Sumida", "name": null }, { "creator_type": "author", "first_name": "Shigekazu", "last_name": "Hidaka", "name": null }, { "creator_type": "author", "first_name": "Toru", "last_name": "Yasutake", "name": null }, { "creator_type": "author", "first_name": "Terumitsu", "last_name": "Sawai", "name": null }, { "creator_type": "author", "first_name": "Ryuji", "last_name": "Hamamoto", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Nanashima", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Nagayasu", "name": null } ], "identifiers": { "doi": { "normalized": "10.21873/anticanres.11540" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "28373470" } }, "mesh": [ { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Aged, 80 and over", "descriptor_ui": "D000369", "major_topic": false }, { "descriptor": "Antibodies, Neoplasm", "descriptor_ui": "D000912", "major_topic": false }, { "descriptor": "Autoantibodies", "descriptor_ui": "D001323", "major_topic": false }, { "descriptor": "Biomarkers, Tumor", "descriptor_ui": "D014408", "major_topic": false }, { "descriptor": "Early Detection of Cancer", "descriptor_ui": "D055088", "major_topic": false }, { "descriptor": "Enzyme-Linked Immunosorbent Assay", "descriptor_ui": "D004797", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Lymphatic Metastasis", "descriptor_ui": "D008207", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Neoplasm Invasiveness", "descriptor_ui": "D009361", "major_topic": false }, { "descriptor": "Neoplasm Staging", "descriptor_ui": "D009367", "major_topic": false }, { "descriptor": "Prognosis", "descriptor_ui": "D011379", "major_topic": false }, { "descriptor": "Retrospective Studies", "descriptor_ui": "D012189", "major_topic": false }, { "descriptor": "Stomach Neoplasms", "descriptor_ui": "D013274", "major_topic": false }, { "descriptor": "Tumor Suppressor Protein p53", "descriptor_ui": "D016159", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Apr", "date_precision": "unknown", "issue": "4", "normalized_date": null, "pages": "1979-1984", "proceedings_title": null, "publisher": "", "title": "Anticancer research", "volume": "37", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Clinical Significance of Serum p53 Antibody in the Early Detection and Poor Prognosis of Gastric Cancer.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Actomyosin generates contractile forces within cells, which have a crucial role in determining the macroscopic mechanical properties of epithelial tissues. Importantly, actin cytoskeleton, which propagates actomyosin contractile forces, forms several characteristic structures in a 3D intracellular space, such as a circumferential actin belt lining adherence junctions and an actin mesh beneath the apical membrane. However, little is known about how epithelial mechanical property depends on the intracellular contractile structures. We performed computational simulations using a 3D vertex model, and demonstrated the longitudinal tensile test of an epithelial tube, whose inside and outside are defined as the apical and basal surfaces, respectively. As a result, these subcellular structures provide the contrary dependence of epithelial stiffness and fracture force on the spontaneous curvature of constituent cells; the epithelial stiffness increases with increasing the spontaneous curvature in the case of belt, meanwhile it decreases in the case of mesh. This qualitative difference emerges from the different anisotropic deformability of apical cell surfaces; while belt preserves isotropic apical cell shapes, mesh does not. Moreover, the difference in the anisotropic deformability determines the frequency of cell rearrangements, which in turn effectively decrease the tube stiffness. These results illustrate the importance of the intracellular contractile structures, which may be regulated to optimize mechanical functions of individual epithelial tissues.", "classifications": [ { "id": "Okuda", "label": "Group Okuda", "parent": "Imayoshi", "type": "group" }, { "id": "Imayoshi", "label": "Team Imayoshi", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Satoru", "last_name": "Okuda", "name": null }, { "creator_type": "author", "first_name": "Katsuyuki", "last_name": "Unoki", "name": null }, { "creator_type": "author", "first_name": "Mototsugu", "last_name": "Eiraku", "name": null }, { "creator_type": "author", "first_name": "Ken-Ichi", "last_name": "Tsubota", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/dgd.12373" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "28707721" } }, "mesh": [ { "descriptor": "Actin Cytoskeleton", "descriptor_ui": "D008841", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Epithelial Cells", "descriptor_ui": "D004847", "major_topic": false }, { "descriptor": "Epithelium", "descriptor_ui": "D004848", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Models, Biological", "descriptor_ui": "D008954", "major_topic": true } ], "publication": { "conference_name": null, "date": "2017 Jun", "date_precision": "unknown", "issue": "5", "normalized_date": null, "pages": "455-464", "proceedings_title": null, "publisher": "", "title": "Development, growth & differentiation", "volume": "59", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "Contractile actin belt and mesh structures provide the opposite dependence of epithelial stiffness on the spontaneous curvature of constituent cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Cells decode information of signaling activation at a scale of tens of minutes by downstream gene expression with a scale of hours to days, leading to cell fate decisions such as cell differentiation. However, no system identification method with such different time scales exists. Here we used compressed sensing technology and developed a system identification method using data of different time scales by recovering signals of missing time points. We measured phosphorylation of ERK and CREB, immediate early gene expression products, and mRNAs of decoder genes for neurite elongation in PC12 cell differentiation and performed system identification, revealing the input–output relationships between signaling and gene expression with sensitivity such as graded or switch-like response and with time delay and gain, representing signal transfer efficiency. We predicted and validated the identified system using pharmacological perturbation. Thus, we provide a versatile method for system identification using data with different time scales.", "classifications": [ { "id": "Kuroda", "label": "Group Kuroda", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Takaho", "last_name": "Tsuchiya", "name": null }, { "creator_type": "author", "first_name": "Masashi", "last_name": "Fujii", "name": null }, { "creator_type": "author", "first_name": "Naoki", "last_name": "Matsuda", "name": null }, { "creator_type": "author", "first_name": "Katsuyuki", "last_name": "Kunida", "name": null }, { "creator_type": "author", "first_name": "Shinsuke", "last_name": "Uda", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Kubota", "name": null }, { "creator_type": "author", "first_name": "Katsumi", "last_name": "Konishi", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Kuroda", "name": null } ], "identifiers": { "doi": { "normalized": "10.1371/journal.pcbi.1005913" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "29281625" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Computational Biology", "descriptor_ui": "D019295", "major_topic": false }, { "descriptor": "Cyclic AMP Response Element-Binding Protein", "descriptor_ui": "D017362", "major_topic": false }, { "descriptor": "Gene Expression", "descriptor_ui": "D015870", "major_topic": true }, { "descriptor": "Kinetics", "descriptor_ui": "D007700", "major_topic": false }, { "descriptor": "MAP Kinase Signaling System", "descriptor_ui": "D020935", "major_topic": false }, { "descriptor": "Models, Biological", "descriptor_ui": "D008954", "major_topic": false }, { "descriptor": "Neurites", "descriptor_ui": "D016501", "major_topic": false }, { "descriptor": "PC12 Cells", "descriptor_ui": "D016716", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": true }, { "descriptor": "Systems Biology", "descriptor_ui": "D049490", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Dec", "date_precision": "unknown", "issue": "12", "normalized_date": null, "pages": "", "proceedings_title": null, "publisher": "", "title": "PLoS Computational Biology", "volume": "13", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "System identification of signaling dependent gene expression with different time-scale data.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "A two-dimensional continuum model of epithelial tissue mechanics was formulated using cellular-level mechanical ingredients and cell morphogenetic processes, including cellular shape changes and cellular rearrangements. This model incorporates stress and deformation tensors, which can be compared with experimental data. Focusing on the interplay between cell shape changes and cell rearrangements, we elucidated dynamical behavior underlying passive relaxation, active contraction-elongation, and tissue shear flow, including a mechanism for contraction-elongation, whereby tissue flows perpendicularly to the axis of cell elongation. This study provides an integrated scheme for the understanding of the orchestration of morphogenetic processes in individual cells to achieve epithelial tissue morphogenesis.", "classifications": [ { "id": "Ishihara", "label": "Group Ishihara", "parent": "Sawai", "type": "group" }, { "id": "Sawai", "label": "Team Sawai", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Shuji", "last_name": "Ishihara", "name": null }, { "creator_type": "author", "first_name": "Philippe", "last_name": "Marcq", "name": null }, { "creator_type": "author", "first_name": "Kaoru", "last_name": "Sugimura", "name": null } ], "identifiers": { "doi": { "normalized": "10.1103/physreve.96.022418" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "28950595" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Biomechanical Phenomena", "descriptor_ui": "D001696", "major_topic": false }, { "descriptor": "Cell Adhesion", "descriptor_ui": "D002448", "major_topic": false }, { "descriptor": "Cell Movement", "descriptor_ui": "D002465", "major_topic": false }, { "descriptor": "Cell Shape", "descriptor_ui": "D048430", "major_topic": false }, { "descriptor": "Computer Simulation", "descriptor_ui": "D003198", "major_topic": false }, { "descriptor": "Drosophila", "descriptor_ui": "D004330", "major_topic": false }, { "descriptor": "Elasticity", "descriptor_ui": "D004548", "major_topic": false }, { "descriptor": "Epithelial Cells", "descriptor_ui": "D004847", "major_topic": false }, { "descriptor": "Epithelium", "descriptor_ui": "D004848", "major_topic": false }, { "descriptor": "Models, Biological", "descriptor_ui": "D008954", "major_topic": true }, { "descriptor": "Morphogenesis", "descriptor_ui": "D009024", "major_topic": false }, { "descriptor": "Stress, Mechanical", "descriptor_ui": "D013314", "major_topic": false }, { "descriptor": "Thermodynamics", "descriptor_ui": "D013816", "major_topic": false }, { "descriptor": "Wings, Animal", "descriptor_ui": "D014921", "major_topic": false }, { "descriptor": "Xenopus", "descriptor_ui": "D014981", "major_topic": false } ], "publication": { "conference_name": null, "date": "2017 Aug", "date_precision": "unknown", "issue": "2-1", "normalized_date": null, "pages": "022418", "proceedings_title": null, "publisher": "", "title": "Physical review. E", "volume": "96", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "From cells to tissue: A continuum model of epithelial mechanics.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Megakaryocytes (Mgks) are terminally differentiated blood cells specified to produce platelets, whereas hematopoietic stem cells (HSCs) are the most undifferentiated blood cells that retain multipotency to produce all kinds of blood cells. As such, these two cell types reside at the bottom and the top of the hematopoietic hierarchy, respectively. In spite of this distance, they share several important cell surface molecules as well as transcription factors.In the conventional step‐wise differentiation model, HSCs gradually lose their self‐renewal capacity and differentiate into multipotent progenitors (MPPs), which is the first branch point of myeloid and lymphoid lineage. In this model, common myeloid progenitors can differentiate into bipotent Mgk/erythroid progenitors (MEPs), and MEPs eventually differentiate into unipotent mature Mgks. However, it has been recently reported that a subpopulation within the HSC and MPP compartments demonstrates an Mgk‐biased differentiation potential. These reports imply that revisions to the HSC‐to‐Mgk differentiation pathway should be discussed. In this review, we summarize recent findings about Mgk differentiation from HSCs and discuss future directions in this research field. Stem Cells Translational Medicine2017;6:1661–1665", "classifications": [ { "id": "Nishikii", "label": "Group Nishikii", "parent": "Shintaku", "type": "group" }, { "id": "Shintaku", "label": "Team Shintaku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Hidekazu", "last_name": "Nishikii", "name": null }, { "creator_type": "author", "first_name": "Naoki", "last_name": "Kurita", "name": null }, { "creator_type": "author", "first_name": "Shigeru", "last_name": "Chiba", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/sctm.16-0490" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "28682009" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Lineage", "descriptor_ui": "D019070", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Megakaryocytes", "descriptor_ui": "D008533", "major_topic": false }, { "descriptor": "Myeloid Progenitor Cells", "descriptor_ui": "D023461", "major_topic": false }, { "descriptor": "Thrombopoiesis", "descriptor_ui": "D034061", "major_topic": true } ], "publication": { "conference_name": null, "date": "2017 Aug", "date_precision": "unknown", "issue": "8", "normalized_date": null, "pages": "1661-1665", "proceedings_title": null, "publisher": "", "title": "Stem Cells Translational Medicine", "volume": "6", "year": 2017 }, "ssbd": { "database": [], "repository": [] }, "title": "The Road Map for Megakaryopoietic Lineage from Hematopoietic Stem/Progenitor Cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "For decades, reactive persulfide species including cysteine persulfide (CysSSH) have been known to exist endogenously in organisms. However, the physiological significance of endogenous persulfides remains poorly understood. That cystathionine beta-synthase and cystathionine gamma-lyase produced CysSSH from cystine was recently demonstrated. An endogenous sulfur transfer system involving CysSSH evidently generates glutathione persulfide (GSSH) that exists at concentrations greater than 100 muM in vivo. Because reactive persulfide species such as CysSSH and GSSH have higher nucleophilicity than parental cysteine (Cys) and glutathione do, these reactive species exhibit strong scavenging activities against oxidants, e.g., hydrogen peroxide, and electrophiles, which contributes to redox signaling regulation. Also, several papers indicated that various proteins and enzymes have Cys polysulfides including CysSSH at their specific Cys residues, which is called protein polysulfidation. Apart from the redox signaling regulatory mechanism, another plausible function of protein polysulfidation is providing protection for protein thiol residues against irreversible chemical modification caused by oxidants and electrophiles. Elucidation of the redox signaling regulatory mechanism of reactive persulfide species including small thiol molecules and thiol-containing proteins should lead to the development of new therapeutic strategies and drug discoveries for oxidative and electrophilic stress-related diseases.", "classifications": [ { "id": "Akaike", "label": "Group Akaike", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Shingo", "last_name": "Kasamatsu", "name": null }, { "creator_type": "author", "first_name": "Akira", "last_name": "Nishimura", "name": null }, { "creator_type": "author", "first_name": "Masanobu", "last_name": "Morita", "name": null }, { "creator_type": "author", "first_name": "Tetsuro", "last_name": "Matsunaga", "name": null }, { "creator_type": "author", "first_name": "Hisyam", "last_name": "Abdul Hamid", "name": null }, { "creator_type": "author", "first_name": "Takaaki", "last_name": "Akaike", "name": null } ], "identifiers": { "doi": { "normalized": "10.3390/molecules21121721" }, "pmcid": { "normalized": "PMC6273478" }, "pmid": { "normalized": "27983699" } }, "mesh": [ { "descriptor": "Cystathionine beta-Synthase", "descriptor_ui": "D003541", "major_topic": false }, { "descriptor": "Cystathionine gamma-Lyase", "descriptor_ui": "D003542", "major_topic": false }, { "descriptor": "Cysteine", "descriptor_ui": "D003545", "major_topic": false }, { "descriptor": "Disulfides", "descriptor_ui": "D004220", "major_topic": false }, { "descriptor": "Glutathione", "descriptor_ui": "D005978", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Hydrogen Peroxide", "descriptor_ui": "D006861", "major_topic": false }, { "descriptor": "Oxidation-Reduction", "descriptor_ui": "D010084", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Superoxides", "descriptor_ui": "D013481", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016 Dec 15", "date_precision": "day", "issue": "12", "normalized_date": "2016-12-15", "pages": "", "proceedings_title": null, "publisher": "", "title": "Molecules (Basel, Switzerland)", "volume": "21", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Redox Signaling Regulated by Cysteine Persulfide and Protein Polysulfidation.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "After DR3 activation, CD4+Foxp3+ regulatory T cells showed a distinct immune phenotype and function in acute GVHD.Prophylactic treatment with agonistic DR3 antibody to recipient mice abrogated the lethal acute GVHD in a time-dependent manner.", "classifications": [ { "id": "Nishikii", "label": "Group Nishikii", "parent": "Shintaku", "type": "group" }, { "id": "Shintaku", "label": "Team Shintaku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Hidekazu", "last_name": "Nishikii", "name": null }, { "creator_type": "author", "first_name": "Byung-Su", "last_name": "Kim", "name": null }, { "creator_type": "author", "first_name": "Yasuhisa", "last_name": "Yokoyama", "name": null }, { "creator_type": "author", "first_name": "Yan", "last_name": "Chen", "name": null }, { "creator_type": "author", "first_name": "Jeanette", "last_name": "Baker", "name": null }, { "creator_type": "author", "first_name": "Antonio", "last_name": "Pierini", "name": null }, { "creator_type": "author", "first_name": "Maite", "last_name": "Alvarez", "name": null }, { "creator_type": "author", "first_name": "Melissa", "last_name": "Mavers", "name": null }, { "creator_type": "author", "first_name": "Kristina", "last_name": "Maas-Bauer", "name": null }, { "creator_type": "author", "first_name": "Yuqiong", "last_name": "Pan", "name": null }, { "creator_type": "author", "first_name": "Shigeru", "last_name": "Chiba", "name": null }, { "creator_type": "author", "first_name": "Robert S.", "last_name": "Negrin", "name": null } ], "identifiers": { "doi": { "normalized": "10.1182/blood-2016-06-723783" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "27760760" } }, "mesh": [ { "descriptor": "Acute Disease", "descriptor_ui": "D000208", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Forkhead Transcription Factors", "descriptor_ui": "D051858", "major_topic": false }, { "descriptor": "Gene Expression Profiling", "descriptor_ui": "D020869", "major_topic": false }, { "descriptor": "Graft vs Host Disease", "descriptor_ui": "D006086", "major_topic": false }, { "descriptor": "Immunophenotyping", "descriptor_ui": "D016130", "major_topic": false }, { "descriptor": "Interleukin-2 Receptor alpha Subunit", "descriptor_ui": "D053645", "major_topic": false }, { "descriptor": "Isoantigens", "descriptor_ui": "D007519", "major_topic": false }, { "descriptor": "Lymphocyte Activation", "descriptor_ui": "D008213", "major_topic": false }, { "descriptor": "Mice, Inbred BALB C", "descriptor_ui": "D008807", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Receptors, Tumor Necrosis Factor, Member 25", "descriptor_ui": "D053219", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": true }, { "descriptor": "T-Lymphocytes, Regulatory", "descriptor_ui": "D050378", "major_topic": false }, { "descriptor": "Transplantation, Homologous", "descriptor_ui": "D014184", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016 Dec 15", "date_precision": "day", "issue": "24", "normalized_date": "2016-12-15", "pages": "2846-2858", "proceedings_title": null, "publisher": "", "title": "Blood", "volume": "128", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "DR3 signaling modulates the function of Foxp3+ regulatory T cells and the severity of acute graft-versus-host disease.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Cell-to-cell variability plays a critical role in cellular responses and decision-making in a population, and transcriptional bursting has been broadly studied by experimental and theoretical approaches as the potential source of cell-to-cell variability. Although molecular mechanisms of transcriptional bursting have been proposed, there is little consensus. An unsolved key question is whether transcriptional bursting is intertwined with many transcriptional regulatory factors or is an intrinsic characteristic of RNA polymerase on DNA. Here we design an in vitro single-molecule measurement system to analyse the kinetics of transcriptional bursting. The results indicate that transcriptional bursting is caused by interplay between RNA polymerases on DNA. The kinetics of in vitro transcriptional bursting is quantitatively consistent with the gene-nonspecific kinetics previously observed in noisy gene expression in vivo. Our kinetic analysis based on a cellular automaton model confirms that arrest and rescue by trailing RNA polymerase intrinsically causes transcriptional bursting.", "classifications": [ { "id": "Iwaki", "label": "Group Iwaki", "parent": "Toyoshima", "type": "group" }, { "id": "Toyoshima", "label": "Team Toyoshima", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Keisuke", "last_name": "Fujita", "name": null }, { "creator_type": "author", "first_name": "Mitsuhiro", "last_name": "Iwaki", "name": null }, { "creator_type": "author", "first_name": "Toshio", "last_name": "Yanagida", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/ncomms13788" }, "pmcid": { "normalized": "PMC5151093" }, "pmid": { "normalized": "27924870" } }, "mesh": [ { "descriptor": "DNA", "descriptor_ui": "D004247", "major_topic": false }, { "descriptor": "DNA-Directed RNA Polymerases", "descriptor_ui": "D012321", "major_topic": false }, { "descriptor": "Microscopy, Atomic Force", "descriptor_ui": "D018625", "major_topic": false }, { "descriptor": "Models, Genetic", "descriptor_ui": "D008957", "major_topic": false }, { "descriptor": "RNA, Messenger", "descriptor_ui": "D012333", "major_topic": false }, { "descriptor": "Transcription Elongation, Genetic", "descriptor_ui": "D061805", "major_topic": false }, { "descriptor": "Transcription Initiation, Genetic", "descriptor_ui": "D061785", "major_topic": false }, { "descriptor": "Transcription, Genetic", "descriptor_ui": "D014158", "major_topic": true } ], "publication": { "conference_name": null, "date": "2016 Dec 7", "date_precision": "day", "issue": "", "normalized_date": "2016-12-07", "pages": "13788", "proceedings_title": null, "publisher": "", "title": "Nature communications", "volume": "7", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Transcriptional bursting is intrinsically caused by interplay between RNA polymerases on DNA.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "In animals and plants, the zygote divides unequally, and the daughter cells inherit different developmental fates to form a proper embryo along the body axis. The cytological events leading to zygote polarization have remained unknown in flowering plants. Here, we report that the two essential components of the cytoskeleton, microtubules and actin filaments, are both disorganized on fertilization and then, arranged to form a transverse ring leading directional cell elongation and longitudinal arrays underlying polar nuclear migration, respectively. These results provide insights into the intracellular dynamics of zygote and the specific roles of cytoskeletons on zygote polarization in flowering plants.", "classifications": [ { "id": "Sato", "label": "Group Sato", "parent": "Tsuchiya", "type": "group" }, { "id": "Tsuchiya", "label": "Team Tsuchiya", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yusuke", "last_name": "Kimata", "name": null }, { "creator_type": "author", "first_name": "Takumi", "last_name": "Higaki", "name": null }, { "creator_type": "author", "first_name": "Tomokazu", "last_name": "Kawashima", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Kurihara", "name": null }, { "creator_type": "author", "first_name": "Yoshikatsu", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Tomomi", "last_name": "Yamada", "name": null }, { "creator_type": "author", "first_name": "Seiichiro", "last_name": "Hasezawa", "name": null }, { "creator_type": "author", "first_name": "Frederic", "last_name": "Berger", "name": null }, { "creator_type": "author", "first_name": "Tetsuya", "last_name": "Higashiyama", "name": null }, { "creator_type": "author", "first_name": "Minako", "last_name": "Ueda", "name": null } ], "identifiers": { "doi": { "normalized": "10.1073/pnas.1613979113" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "27911812" } }, "mesh": [ { "descriptor": "Actin Cytoskeleton", "descriptor_ui": "D008841", "major_topic": false }, { "descriptor": "Arabidopsis", "descriptor_ui": "D017360", "major_topic": false }, { "descriptor": "Cell Division", "descriptor_ui": "D002455", "major_topic": false }, { "descriptor": "Cell Polarity", "descriptor_ui": "D016764", "major_topic": true }, { "descriptor": "Fertilization", "descriptor_ui": "D005306", "major_topic": false }, { "descriptor": "Microtubules", "descriptor_ui": "D008870", "major_topic": false }, { "descriptor": "Seeds", "descriptor_ui": "D012639", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016 Dec 6", "date_precision": "day", "issue": "49", "normalized_date": "2016-12-06", "pages": "14157-14162", "proceedings_title": null, "publisher": "", "title": "Proceedings of the National Academy of Sciences of the United States of America", "volume": "113", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Cytoskeleton dynamics control the first asymmetric cell division in Arabidopsis zygote.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The in vitro derivation and propagation of spermatogonial stem cells (SSCs) from pluripotent stem cells (PSCs) is a key goal in reproductive science. We show here that when aggregated with embryonic testicular somatic cells (reconstituted testes), primordial germ cell-like cells (PGCLCs) induced from mouse embryonic stem cells differentiate into spermatogonia-like cells in vitro and are expandable as cells that resemble germline stem cells (GSCs), a primary cell line with SSC activity. Remarkably, GSC-like cells (GSCLCs), but not PGCLCs, colonize adult testes and, albeit less effectively than GSCs, contribute to spermatogenesis and fertile offspring. Whole-genome analyses reveal that GSCLCs exhibit aberrant methylation at vulnerable regulatory elements, including those critical for spermatogenesis, which may restrain their spermatogenic potential. Our study establishes a strategy for the in vitro derivation of SSC activity from PSCs, which, we propose, relies on faithful epigenomic regulation.", "classifications": [ { "id": "Yamamoto", "label": "Group Yamamoto", "parent": "Toyoshima", "type": "group" }, { "id": "Toyoshima", "label": "Team Toyoshima", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yukiko", "last_name": "Ishikura", "name": null }, { "creator_type": "author", "first_name": "Yukihiro", "last_name": "Yabuta", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Ohta", "name": null }, { "creator_type": "author", "first_name": "Katsuhiko", "last_name": "Hayashi", "name": null }, { "creator_type": "author", "first_name": "Tomonori", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Ikuhiro", "last_name": "Okamoto", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Kazuki", "last_name": "Kurimoto", "name": null }, { "creator_type": "author", "first_name": "Kenjiro", "last_name": "Shirane", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Sasaki", "name": null }, { "creator_type": "author", "first_name": "Mitinori", "last_name": "Saitou", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.celrep.2016.11.026" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "27926879" } }, "mesh": [ { "descriptor": "Adult Germline Stem Cells", "descriptor_ui": "D000072956", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Proliferation", "descriptor_ui": "D049109", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Pluripotent Stem Cells", "descriptor_ui": "D039904", "major_topic": false }, { "descriptor": "Spermatogenesis", "descriptor_ui": "D013091", "major_topic": false }, { "descriptor": "Spermatogonia", "descriptor_ui": "D013093", "major_topic": false }, { "descriptor": "Testis", "descriptor_ui": "D013737", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016 Dec 6", "date_precision": "day", "issue": "10", "normalized_date": "2016-12-06", "pages": "2789-2804", "proceedings_title": null, "publisher": "", "title": "Cell reports", "volume": "17", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "In Vitro Derivation and Propagation of Spermatogonial Stem Cell Activity from Mouse Pluripotent Stem Cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "SIRT1 acts as a cellular sensor to detect energy availability and modulates fat and glucose metabolism. This study assessed the effects of self-reported calorie restriction (CR) and exercise on correlations between SIRT1 polymorphisms and body mass index (BMI) and long-term weight change. This cross-sectional study enrolled 4023 subjects aged 35-69years (1847 men and 2176 women) selected from participants in the Japan Multi-Institutional Collaborative Cohort Study. This study was based on a self-administered questionnaire. No significant correlations between SIRT1 polymorphisms and BMI or long-term weight change were found in either the CR or the active groups. In the no-CR group, women with the rs1467568 G allele had a higher BMI than women without (p=0.02). Moreover, women with the rs7895833 A or rs1467568 G allele gained more weight from the age of 20years than women without these alleles (p=0.03 for rs7895833 and p=0.003 for rs1467568). In addition, the odds ratios (95% confidence intervals) of these alleles for overweight (BMI >27.5kg/m(2)) were significantly high in the no-CR women group (1.78 (1.06-2.99) for rs7895833 and 1.88 (1.13-3.15) for rs1467568) but not in the CR group. The results of this study suggest that CR might override the genetic contributions of the SIRT1 rs7895833 A and rs1467568 G alleles to BMI and long-term weight change.", "classifications": [ { "id": "Tanaka", "label": "Group Tanaka", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Takahiro", "last_name": "Higashibata", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Wakai", "name": null }, { "creator_type": "author", "first_name": "Mariko", "last_name": "Naito", "name": null }, { "creator_type": "author", "first_name": "Emi", "last_name": "Morita", "name": null }, { "creator_type": "author", "first_name": "Asahi", "last_name": "Hishida", "name": null }, { "creator_type": "author", "first_name": "Nobuyuki", "last_name": "Hamajima", "name": null }, { "creator_type": "author", "first_name": "Megumi", "last_name": "Hara", "name": null }, { "creator_type": "author", "first_name": "Sadao", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Satoyo", "last_name": "Hosono", "name": null }, { "creator_type": "author", "first_name": "Naoyuki", "last_name": "Takashima", "name": null }, { "creator_type": "author", "first_name": "Keizo", "last_name": "Ohnaka", "name": null }, { "creator_type": "author", "first_name": "Akihiko", "last_name": "Takada", "name": null }, { "creator_type": "author", "first_name": "Haruo", "last_name": "Mikami", "name": null }, { "creator_type": "author", "first_name": "Yoshiyuki", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Hirokazu", "last_name": "Uemura", "name": null }, { "creator_type": "author", "first_name": "Michiaki", "last_name": "Kubo", "name": null }, { "creator_type": "author", "first_name": "Hideo", "last_name": "Tanaka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.gene.2016.08.051" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "27591970" } }, "mesh": [ { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Alleles", "descriptor_ui": "D000483", "major_topic": true }, { "descriptor": "Body Mass Index", "descriptor_ui": "D015992", "major_topic": true }, { "descriptor": "Caloric Restriction", "descriptor_ui": "D031204", "major_topic": true }, { "descriptor": "Cross-Sectional Studies", "descriptor_ui": "D003430", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Overweight", "descriptor_ui": "D050177", "major_topic": false }, { "descriptor": "Polymorphism, Genetic", "descriptor_ui": "D011110", "major_topic": true }, { "descriptor": "Self Report", "descriptor_ui": "D057566", "major_topic": false }, { "descriptor": "Sirtuin 1", "descriptor_ui": "D056564", "major_topic": false }, { "descriptor": "Time Factors", "descriptor_ui": "D013997", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016 Dec 5", "date_precision": "day", "issue": "1", "normalized_date": "2016-12-05", "pages": "16-22", "proceedings_title": null, "publisher": "", "title": "Gene", "volume": "594", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Effects of self-reported calorie restriction on correlations between SIRT1 polymorphisms and body mass index and long-term weight change.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "We present a copper-catalyzed oxidative cyclization of beta,gamma-unsaturated hydrazones, utilizing molecular oxygen as a stoichiometric oxidant. The methodology provides distinct classes of pyrazoles simply by changing the reaction solvent. Tris-substituted pyrazoles, having a ketone functionality at the C-5 position, were obtained as the major product in ethanol, while di-substituted pyrazoles were predominantly formed in 1,1,1,3,3,3-hexafluoro-2-propanol.", "classifications": [ { "id": "Sodeoka", "label": "Group Sodeoka", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Florian", "last_name": "Punner", "name": null }, { "creator_type": "author", "first_name": "Yoshihiro", "last_name": "Sohtome", "name": null }, { "creator_type": "author", "first_name": "Mikiko", "last_name": "Sodeoka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1039/c6cc06935e" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "27805203" } }, "mesh": [ { "descriptor": "Catalysis", "descriptor_ui": "D002384", "major_topic": false }, { "descriptor": "Copper", "descriptor_ui": "D003300", "major_topic": false }, { "descriptor": "Molecular Structure", "descriptor_ui": "D015394", "major_topic": false }, { "descriptor": "Oxidation-Reduction", "descriptor_ui": "D010084", "major_topic": false }, { "descriptor": "Oxygen", "descriptor_ui": "D010100", "major_topic": false }, { "descriptor": "Pyrazoles", "descriptor_ui": "D011720", "major_topic": false }, { "descriptor": "Solvents", "descriptor_ui": "D012997", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016 Dec 1", "date_precision": "day", "issue": "98", "normalized_date": "2016-12-01", "pages": "14093-14096", "proceedings_title": null, "publisher": "", "title": "Chemical communications (Cambridge, England)", "volume": "52", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Solvent-dependent copper-catalyzed synthesis of pyrazoles under aerobic conditions.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The acquired immune system, mainly composed of T and B lymphocytes, plays a key role in protecting the host from infection. It is important and technically challenging to identify cell types and their activation status in living and intact immune cells, without staining or killing the cells. Using Raman spectroscopy, we succeeded in discriminating between living T cells and B cells, and visualized the activation status of living T cells without labeling. Although the Raman spectra of T cells and B cells were similar, they could be distinguished by discriminant analysis of the principal components. Raman spectra of activated T cells with anti-CD3 and anti-CD28 antibodies largely differed compared to that of naive T cells, enabling the prediction of T cell activation status at a single cell level. Our analysis revealed that the spectra of individual T cells gradually change from the pattern of naive T cells to that of activated T cells during the first 24 h of activation, indicating that changes in Raman spectra reflect slow changes rather than rapid changes in cell state during activation. Our results indicate that the Raman spectrum enables the detection of dynamic changes in individual cell state scattered in a heterogeneous population.", "classifications": [ { "id": "Fujita", "label": "Group Fujita", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Taro", "last_name": "Ichimura", "name": null }, { "creator_type": "author", "first_name": "Liang-da", "last_name": "Chiu", "name": null }, { "creator_type": "author", "first_name": "Katsumasa", "last_name": "Fujita", "name": null }, { "creator_type": "author", "first_name": "Hiroaki", "last_name": "Machiyama", "name": null }, { "creator_type": "author", "first_name": "Tomoyuki", "last_name": "Yamaguchi", "name": null }, { "creator_type": "author", "first_name": "Tomonobu M.", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Hideaki", "last_name": "Fujita", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/srep37562" }, "pmcid": { "normalized": "PMC5120326" }, "pmid": { "normalized": "27876845" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "B-Lymphocytes", "descriptor_ui": "D001402", "major_topic": false }, { "descriptor": "Lymphocyte Activation", "descriptor_ui": "D008213", "major_topic": false }, { "descriptor": "Mice, Inbred BALB C", "descriptor_ui": "D008807", "major_topic": false }, { "descriptor": "Mice, Transgenic", "descriptor_ui": "D008822", "major_topic": false }, { "descriptor": "Spectrum Analysis, Raman", "descriptor_ui": "D013059", "major_topic": false }, { "descriptor": "T-Lymphocytes", "descriptor_ui": "D013601", "major_topic": false }, { "descriptor": "Time Factors", "descriptor_ui": "D013997", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016 Nov 23", "date_precision": "day", "issue": "", "normalized_date": "2016-11-23", "pages": "37562", "proceedings_title": null, "publisher": "", "title": "Scientific reports", "volume": "6", "year": 2016 }, "ssbd": { "database": [ "ssbd-database-000053" ], "repository": [ "ssbd-repos-000053" ] }, "title": "Non-label immune cell state prediction using Raman spectroscopy.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Secretion of insulin transiently increases after eating, resulting in a high circulating concentration. Fasting limits insulin secretion, resulting in a low concentration of insulin in the circulation. We analyzed transcriptional responses to different temporal patterns and doses of insulin in the hepatoma FAO cells and identified 13 up-regulated and 16 down-regulated insulin-responsive genes (IRGs). The up-regulated IRGs responded more rapidly than did the down-regulated IRGs to transient stepwise or pulsatile increases in insulin concentration, whereas the down-regulated IRGs were repressed at lower concentrations of insulin than those required to stimulate the up-regulated IRGs. Mathematical modeling of the insulin response as two stages-(i) insulin signaling to transcription and (ii)transcription and mRNA stability-indicated that the first stage was the more rapid stage for the down-regulated IRGs, whereas the second stage of transcription was the more rapid stage for the up-regulated IRGs. A subset of the IRGs that were up-regulated or down-regulated in the FAO cells was similarly regulated in the livers of rats injected with a single dose of insulin. Thus, not only can cells respond to insulin but they can also interpret the intensity and pattern of signal to produce distinct transcriptional responses. These results provide insight that may be useful in treating obesity and type 2 diabetes associated with aberrant insulin production or tissue responsiveness.", "classifications": [ { "id": "Kuroda", "label": "Group Kuroda", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Takanori", "last_name": "Sano", "name": null }, { "creator_type": "author", "first_name": "Kentaro", "last_name": "Kawata", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Ohno", "name": null }, { "creator_type": "author", "first_name": "Katsuyuki", "last_name": "Yugi", "name": null }, { "creator_type": "author", "first_name": "Hiroaki", "last_name": "Kakuda", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Kubota", "name": null }, { "creator_type": "author", "first_name": "Shinsuke", "last_name": "Uda", "name": null }, { "creator_type": "author", "first_name": "Masashi", "last_name": "Fujii", "name": null }, { "creator_type": "author", "first_name": "Katsuyuki", "last_name": "Kunida", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Hoshino", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Hatano", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Miharu", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Yutaka", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Kuroda", "name": null } ], "identifiers": { "doi": { "normalized": "10.1126/scisignal.aaf3739" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "27879394" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Down-Regulation", "descriptor_ui": "D015536", "major_topic": false }, { "descriptor": "Insulin", "descriptor_ui": "D007328", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Up-Regulation", "descriptor_ui": "D015854", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016 Nov 22", "date_precision": "day", "issue": "455", "normalized_date": "2016-11-22", "pages": "ra112", "proceedings_title": null, "publisher": "", "title": "Science signaling", "volume": "9", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Selective control of up-regulated and down-regulated genes by temporal patterns and doses of insulin.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "MOTIVATION: Rapid advances in live-cell imaging analysis and mathematical modeling have produced a large amount of quantitative data on spatiotemporal dynamics of biological objects ranging from molecules to organisms. There is now a crucial need to bring these large amounts of quantitative biological dynamics data together centrally in a coherent and systematic manner. This will facilitate the reuse of this data for further analysis. RESULTS: We have developed the Systems Science of Biological Dynamics database (SSBD) to store and share quantitative biological dynamics data. SSBD currently provides 311 sets of quantitative data for single molecules, nuclei and whole organisms in a wide variety of model organisms from Escherichia coli to Mus musculus The data are provided in Biological Dynamics Markup Language format and also through a REST API. In addition, SSBD provides 188 sets of time-lapse microscopy images from which the quantitative data were obtained and software tools for data visualization and analysis. AVAILABILITY AND IMPLEMENTATION: SSBD is accessible at http://ssbd.qbic.riken.jp CONTACT: sonami@riken.jp.", "classifications": [ { "id": "Onami", "label": "Group Onami", "parent": "Fujiwara", "type": "group" }, { "id": "Fujiwara", "label": "Team Fujiwara", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yukako", "last_name": "Tohsato", "name": null }, { "creator_type": "author", "first_name": "Kenneth H. L.", "last_name": "Ho", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Kyoda", "name": null }, { "creator_type": "author", "first_name": "Shuichi", "last_name": "Onami", "name": null } ], "identifiers": { "doi": { "normalized": "10.1093/bioinformatics/btw417" }, "pmcid": { "normalized": "PMC5181557" }, "pmid": { "normalized": "27412095" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Biological Phenomena", "descriptor_ui": "D001686", "major_topic": true }, { "descriptor": "Databases, Factual", "descriptor_ui": "D016208", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Microscopy", "descriptor_ui": "D008853", "major_topic": false }, { "descriptor": "Software", "descriptor_ui": "D012984", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016 Nov 15", "date_precision": "day", "issue": "22", "normalized_date": "2016-11-15", "pages": "3471-3479", "proceedings_title": null, "publisher": "", "title": "Bioinformatics (Oxford, England)", "volume": "32", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "SSBD: a database of quantitative data of spatiotemporal dynamics of biological phenomena.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Accumulating evidence suggests that transcriptional regulation is required for maintenance of long-term memories (LTMs). Here we characterize global transcriptional and epigenetic changes that occur during LTM storage in the Drosophila mushroom bodies (MBs), structures important for memory. Although LTM formation requires the CREB transcription factor and its coactivator, CBP, subsequent early maintenance requires CREB and a different coactivator, CRTC. Late maintenance becomes CREB independent and instead requires the transcription factor Bx. Bx expression initially depends on CREB/CRTC activity, but later becomes CREB/CRTC independent. The timing of the CREB/CRTC early maintenance phase correlates with the time window for LTM extinction and we identify different subsets of CREB/CRTC target genes that are required for memory maintenance and extinction. Furthermore, we find that prolonging CREB/CRTC-dependent transcription extends the time window for LTM extinction. Our results demonstrate the dynamic nature of stored memory and its regulation by shifting transcription systems in the MBs.", "classifications": [ { "id": "Yamamoto", "label": "Group Yamamoto", "parent": "Toyoshima", "type": "group" }, { "id": "Toyoshima", "label": "Team Toyoshima", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yukinori", "last_name": "Hirano", "name": null }, { "creator_type": "author", "first_name": "Kunio", "last_name": "Ihara", "name": null }, { "creator_type": "author", "first_name": "Tomoko", "last_name": "Masuda", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Ikuko", "last_name": "Iwata", "name": null }, { "creator_type": "author", "first_name": "Aya", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Hiroko", "last_name": "Awata", "name": null }, { "creator_type": "author", "first_name": "Naosuke", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Mai", "last_name": "Takakura", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Junjiro", "last_name": "Horiuchi", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Okuno", "name": null }, { "creator_type": "author", "first_name": "Minoru", "last_name": "Saitoe", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/ncomms13471" }, "pmcid": { "normalized": "PMC5114576" }, "pmid": { "normalized": "27841260" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Animals, Genetically Modified", "descriptor_ui": "D030801", "major_topic": false }, { "descriptor": "Cyclic AMP Response Element-Binding Protein", "descriptor_ui": "D017362", "major_topic": false }, { "descriptor": "Drosophila melanogaster", "descriptor_ui": "D004331", "major_topic": false }, { "descriptor": "Drosophila Proteins", "descriptor_ui": "D029721", "major_topic": false }, { "descriptor": "Gene Expression Profiling", "descriptor_ui": "D020869", "major_topic": false }, { "descriptor": "Gene Expression Regulation", "descriptor_ui": "D005786", "major_topic": true }, { "descriptor": "Gene Ontology", "descriptor_ui": "D063990", "major_topic": false }, { "descriptor": "Memory, Long-Term", "descriptor_ui": "D057567", "major_topic": true }, { "descriptor": "Mushroom Bodies", "descriptor_ui": "D024521", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Transcription Factors", "descriptor_ui": "D014157", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016 Nov 14", "date_precision": "day", "issue": "", "normalized_date": "2016-11-14", "pages": "13471", "proceedings_title": null, "publisher": "", "title": "Nature communications", "volume": "7", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Shifting transcriptional machinery is required for long-term memory maintenance and modification in Drosophila mushroom bodies.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Reactive persulfide species such as glutathione persulfide (GSSH) are highly abundant biomolecules. Persulfide dioxygenase (also called ethylmalonic encephalopathy protein 1, ETHE1) reportedly metabolizes GSSH to GSH with simultaneous oxygen consumption. How ETHE1 activity is regulated is still unclear, however. In this study, we describe the possible role of protein polysulfidation in the catalytic activity of ETHE1. We first found that ETHE1 catalyzed the persulfide dioxygenase reaction mostly for glutathione polysulfides, GS-(S)(n)-H, as well as for GSSH, but not for other endogenous persulfides such as cysteine and homocysteine persulfides/polysulfides. We then developed a novel method to detect protein polysulfidation and named it the polyethylene glycol-conjugated maleimide-labeling gel shift assay (PMSA). PMSA analysis indicated that most cysteine residues in ETHE1 were polysulfidated. Site-directed mutagenesis of cysteine residues in ETHE1 combined with liquid chromatography tandem mass spectrometry for polysulfidation determination surprisingly indicated that the Cys247 residue was important for polysulfidation of other Cys residues and that the C247S mutant possessed no persulfide dioxygenase activity. These results suggested that ETHE1 is a major enzyme regulating endogenous GSSH/GS-(S)(n)-H and that its activity is controlled by polysulfidation of the Cys247 residue.", "classifications": [ { "id": "Akaike", "label": "Group Akaike", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Minkyung", "last_name": "Jung", "name": null }, { "creator_type": "author", "first_name": "Shingo", "last_name": "Kasamatsu", "name": null }, { "creator_type": "author", "first_name": "Tetsuro", "last_name": "Matsunaga", "name": null }, { "creator_type": "author", "first_name": "Soichiro", "last_name": "Akashi", "name": null }, { "creator_type": "author", "first_name": "Katsuhiko", "last_name": "Ono", "name": null }, { "creator_type": "author", "first_name": "Akira", "last_name": "Nishimura", "name": null }, { "creator_type": "author", "first_name": "Masanobu", "last_name": "Morita", "name": null }, { "creator_type": "author", "first_name": "Hisyam", "last_name": "Abdul Hamid", "name": null }, { "creator_type": "author", "first_name": "Shigemoto", "last_name": "Fujii", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Kitamura", "name": null }, { "creator_type": "author", "first_name": "Tomohiro", "last_name": "Sawa", "name": null }, { "creator_type": "author", "first_name": "Tomoaki", "last_name": "Ida", "name": null }, { "creator_type": "author", "first_name": "Hozumi", "last_name": "Motohashi", "name": null }, { "creator_type": "author", "first_name": "Takaaki", "last_name": "Akaike", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.bbrc.2016.10.022" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "27742479" } }, "mesh": [ { "descriptor": "A549 Cells", "descriptor_ui": "D000072283", "major_topic": false }, { "descriptor": "Cysteine", "descriptor_ui": "D003545", "major_topic": false }, { "descriptor": "Dioxygenases", "descriptor_ui": "D049308", "major_topic": false }, { "descriptor": "Disulfides", "descriptor_ui": "D004220", "major_topic": false }, { "descriptor": "Glutathione", "descriptor_ui": "D005978", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mitochondrial Proteins", "descriptor_ui": "D024101", "major_topic": false }, { "descriptor": "Nucleocytoplasmic Transport Proteins", "descriptor_ui": "D029543", "major_topic": false }, { "descriptor": "Proteins", "descriptor_ui": "D011506", "major_topic": false }, { "descriptor": "Substrate Specificity", "descriptor_ui": "D013379", "major_topic": false }, { "descriptor": "Sulfides", "descriptor_ui": "D013440", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016 Nov 11", "date_precision": "day", "issue": "2", "normalized_date": "2016-11-11", "pages": "180-186", "proceedings_title": null, "publisher": "", "title": "Biochemical and biophysical research communications", "volume": "480", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Protein polysulfidation-dependent persulfide dioxygenase activity of ethylmalonic encephalopathy protein 1.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The upbuilding of dirhodium tetracarboxylate paddlewheels into porous architectures is still challenging because of the inertness of equatorial carboxylates for ligand-exchange reaction. Here we demonstrate the synthesis of a new family of metal-organic cuboctahedra by connecting dirhodium units through 1,3-benzenedicarboxylate and assembling cuboctahedra as porous solids. Carbon monoxide and nitric oxide were strongly trapped in the internal cavity thanks to the strong affinity of unsaturated axial coordination sites of dirhodium centers.", "classifications": [ { "id": "Hijikata", "label": "Group Hijikata", "parent": "Tsuchiya", "type": "group" }, { "id": "Tsuchiya", "label": "Team Tsuchiya", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Shuhei", "last_name": "Furukawa", "name": null }, { "creator_type": "author", "first_name": "Nao", "last_name": "Horike", "name": null }, { "creator_type": "author", "first_name": "Mio", "last_name": "Kondo", "name": null }, { "creator_type": "author", "first_name": "Yuh", "last_name": "Hijikata", "name": null }, { "creator_type": "author", "first_name": "Arnau", "last_name": "Carne-Sanchez", "name": null }, { "creator_type": "author", "first_name": "Patrick", "last_name": "Larpent", "name": null }, { "creator_type": "author", "first_name": "Nicolas", "last_name": "Louvain", "name": null }, { "creator_type": "author", "first_name": "Stephane", "last_name": "Diring", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Ryotaro", "last_name": "Matsuda", "name": null }, { "creator_type": "author", "first_name": "Ryuji", "last_name": "Kawano", "name": null }, { "creator_type": "author", "first_name": "Susumu", "last_name": "Kitagawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/acs.inorgchem.6b02091" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "27748586" } }, "mesh": [], "publication": { "conference_name": null, "date": "2016 Nov 7", "date_precision": "day", "issue": "21", "normalized_date": "2016-11-07", "pages": "10843-10846", "proceedings_title": null, "publisher": "", "title": "Inorganic chemistry", "volume": "55", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Rhodium-Organic Cuboctahedra as Porous Solids with Strong Binding Sites.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "We previously demonstrated that mouse embryonic stem cell (mESC)-derived retinal epithelium self-forms an optic cup-like structure. In the developing retina, the dorsal and ventral sides differ in terms of local gene expression and morphological features. This aspect has not yet been shown in vitro Here, we demonstrate that mESC-derived retinal tissue spontaneously acquires polarity reminiscent of the dorsal-ventral (D-V) patterning of the embryonic retina. Tbx5 and Vax2 were expressed in a mutually exclusive manner, as seen in vivo Three-dimensional morphometric analysis showed that the in vitro-formed optic cup often contains cleft structures resembling the embryonic optic fissure. To elucidate the mechanisms underlying the spontaneous D-V polarization of mESC-derived retina, we examined the effects of patterning factors, and found that endogenous BMP signaling plays a predominant role in the dorsal specification. Further analysis revealed that canonical Wnt signaling, which was spontaneously activated at the proximal region, acts upstream of BMP signaling for dorsal specification. These observations suggest that D-V polarity could be established within the self-formed retinal neuroepithelium by intrinsic mechanisms involving the spatiotemporal regulation of canonical Wnt and BMP signals.", "classifications": [ { "id": "Okuda", "label": "Group Okuda", "parent": "Imayoshi", "type": "group" }, { "id": "Imayoshi", "label": "Team Imayoshi", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yuiko", "last_name": "Hasegawa", "name": null }, { "creator_type": "author", "first_name": "Nozomu", "last_name": "Takata", "name": null }, { "creator_type": "author", "first_name": "Satoru", "last_name": "Okuda", "name": null }, { "creator_type": "author", "first_name": "Masako", "last_name": "Kawada", "name": null }, { "creator_type": "author", "first_name": "Mototsugu", "last_name": "Eiraku", "name": null }, { "creator_type": "author", "first_name": "Yoshiki", "last_name": "Sasai", "name": null } ], "identifiers": { "doi": { "normalized": "10.1242/dev.134601" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "27633992" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Body Patterning", "descriptor_ui": "D019521", "major_topic": false }, { "descriptor": "Cell Polarity", "descriptor_ui": "D016764", "major_topic": false }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Embryo, Mammalian", "descriptor_ui": "D004622", "major_topic": false }, { "descriptor": "Embryonic Stem Cells", "descriptor_ui": "D053595", "major_topic": false }, { "descriptor": "Gene Expression Regulation, Developmental", "descriptor_ui": "D018507", "major_topic": false }, { "descriptor": "Gene Knockdown Techniques", "descriptor_ui": "D055785", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Organ Culture Techniques", "descriptor_ui": "D009924", "major_topic": false }, { "descriptor": "Organogenesis", "descriptor_ui": "D038081", "major_topic": false }, { "descriptor": "Retina", "descriptor_ui": "D012160", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016 Nov 1", "date_precision": "day", "issue": "21", "normalized_date": "2016-11-01", "pages": "3895-3906", "proceedings_title": null, "publisher": "", "title": "Development (Cambridge, England)", "volume": "143", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Emergence of dorsal-ventral polarity in ESC-derived retinal tissue.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Identification of small-molecule-binding sites in protein is important for drug discovery and analysis of protein function. Modified amino-acid residue(s) can be identified by proteolytic cleavage followed by liquid chromatography-mass spectrometry (LC-MS), but this is often hindered by the complexity of the peptide mixtures. We have developed alkyne-tag Raman screening (ATRaS) for identifying binding sites. In ATRaS, small molecules are tagged with alkyne and form covalent bond with proteins. After proteolysis and HPLC, fractions containing the labeled peptides with alkyne tags are detected by means of surface-enhanced Raman scattering (SERS) using silver nanoparticles and sent to MS/MS to identify the binding site. The use of SERS realizes high sensitivity (detection limit: approximately 100 femtomole) and reproducibility in the peptide screening. By using an automated ATRaS system, we successfully identified the inhibitor-binding site in cysteine protease cathepsin B, a potential drug target and prognostic marker for tumor metastasis. We further showed that the ATRaS system works for complex mixtures of trypsin-digested cell lysate. The ATRaS technology, which provides high molecular selectivity to LC-MS analysis, has potential to contribute in various research fields, such as drug discovery, proteomics, metabolomics and chemical biology.", "classifications": [ { "id": "Fujita", "label": "Group Fujita", "parent": "Fujita", "type": "group" }, { "id": "Sodeoka", "label": "Group Sodeoka", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Jun", "last_name": "Ando", "name": null }, { "creator_type": "author", "first_name": "Miwako", "last_name": "Asanuma", "name": null }, { "creator_type": "author", "first_name": "Kosuke", "last_name": "Dodo", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Yamakoshi", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Kawata", "name": null }, { "creator_type": "author", "first_name": "Katsumasa", "last_name": "Fujita", "name": null }, { "creator_type": "author", "first_name": "Mikiko", "last_name": "Sodeoka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/jacs.6b06003" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "27723308" } }, "mesh": [], "publication": { "conference_name": null, "date": "2016 Oct 26", "date_precision": "day", "issue": "42", "normalized_date": "2016-10-26", "pages": "13901-13910", "proceedings_title": null, "publisher": "", "title": "Journal of the American Chemical Society", "volume": "138", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Alkyne-Tag SERS Screening and Identification of Small-Molecule-Binding Sites in Protein.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Some colloidal suspensions contain two types of particles-small and large particles-to improve the lubricating ability, light absorptivity, and so forth. Structural and chemical analyses of such colloidal suspensions are often performed to understand their properties. In a structural analysis study, the observation of the number density distribution of small particles around a large particle (gLS) is difficult because these particles are randomly moving within the colloidal suspension by Brownian motion. We obtain gLS using the data from a line optical tweezer (LOT) that can measure the potential of mean force between two large colloidal particles (PhiLL). We propose a theory that transforms PhiLL into gLS. The transform theory is explained in detail and tested. We demonstrate for the first time that LOT can be used for the structural analysis of a colloidal suspension. LOT combined with the transform theory will facilitate structural analyses of the colloidal suspensions, which is important for both understanding colloidal properties and developing colloidal products.", "classifications": [ { "id": "Iwaki", "label": "Group Iwaki", "parent": "Toyoshima", "type": "group" }, { "id": "Toyoshima", "label": "Team Toyoshima", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Ken-Ichi", "last_name": "Amano", "name": null }, { "creator_type": "author", "first_name": "Mitsuhiro", "last_name": "Iwaki", "name": null }, { "creator_type": "author", "first_name": "Kota", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Kazuhiro", "last_name": "Fukami", "name": null }, { "creator_type": "author", "first_name": "Naoya", "last_name": "Nishi", "name": null }, { "creator_type": "author", "first_name": "Ohgi", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Tetsuo", "last_name": "Sakka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/acs.langmuir.6b02628" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "27683951" } }, "mesh": [], "publication": { "conference_name": null, "date": "2016 Oct 25", "date_precision": "day", "issue": "42", "normalized_date": "2016-10-25", "pages": "11063-11070", "proceedings_title": null, "publisher": "", "title": "Langmuir : the ACS journal of surfaces and colloids", "volume": "32", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Number Density Distribution of Small Particles around a Large Particle: Structural Analysis of a Colloidal Suspension.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The germ cell lineage ensures reproduction and heredity. The mechanism for germ cell specification in primates, including humans, has remained unknown. In primates, upon implantation the pluripotent epiblast segregates the amnion, an extra-embryonic membrane eventually ensheathing an embryo, and thereafter initiates gastrulation to generate three germ layers. Here, we show that in cynomolgus monkeys, the SOX17/TFAP2C/BLIMP1-positive primordial germ cells (cyPGCs) originate from the dorsal amnion at embryonic day 11 (E11) prior to gastrulation. cyPGCs appear to migrate down the amnion and, through proliferation and recruitment from the posterior amnion, expand in number around the posterior yolk sac by E17. Remarkably, the amnion itself expresses BMP4 and WNT3A, cytokines potentially critical for cyPGC specification, and responds primarily to them. Moreover, human PGC-like cells in vitro exhibit a transcriptome similar to cyPGCs just after specification. Our study identifies the origin of PGCs and a unique function of the nascent amnion in primates.", "classifications": [ { "id": "Yamamoto", "label": "Group Yamamoto", "parent": "Toyoshima", "type": "group" }, { "id": "Toyoshima", "label": "Team Toyoshima", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Kotaro", "last_name": "Sasaki", "name": null }, { "creator_type": "author", "first_name": "Tomonori", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Ikuhiro", "last_name": "Okamoto", "name": null }, { "creator_type": "author", "first_name": "Yukihiro", "last_name": "Yabuta", "name": null }, { "creator_type": "author", "first_name": "Chizuru", "last_name": "Iwatani", "name": null }, { "creator_type": "author", "first_name": "Hideaki", "last_name": "Tsuchiya", "name": null }, { "creator_type": "author", "first_name": "Yasunari", "last_name": "Seita", "name": null }, { "creator_type": "author", "first_name": "Shinichiro", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Naoto", "last_name": "Shiraki", "name": null }, { "creator_type": "author", "first_name": "Tetsuya", "last_name": "Takakuwa", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Mitinori", "last_name": "Saitou", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.devcel.2016.09.007" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "27720607" } }, "mesh": [ { "descriptor": "Amnion", "descriptor_ui": "D000650", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Autocrine Communication", "descriptor_ui": "D019898", "major_topic": false }, { "descriptor": "Cell Lineage", "descriptor_ui": "D019070", "major_topic": true }, { "descriptor": "Cell Movement", "descriptor_ui": "D002465", "major_topic": false }, { "descriptor": "Embryo, Mammalian", "descriptor_ui": "D004622", "major_topic": false }, { "descriptor": "Fetus", "descriptor_ui": "D005333", "major_topic": false }, { "descriptor": "Germ Cells", "descriptor_ui": "D005854", "major_topic": false }, { "descriptor": "Gonads", "descriptor_ui": "D006066", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Macaca fascicularis", "descriptor_ui": "D008252", "major_topic": false }, { "descriptor": "Mesoderm", "descriptor_ui": "D008648", "major_topic": false }, { "descriptor": "Models, Biological", "descriptor_ui": "D008954", "major_topic": false }, { "descriptor": "Pluripotent Stem Cells", "descriptor_ui": "D039904", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Transcription Factors", "descriptor_ui": "D014157", "major_topic": false }, { "descriptor": "Transcription, Genetic", "descriptor_ui": "D014158", "major_topic": false }, { "descriptor": "Transcriptome", "descriptor_ui": "D059467", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016 Oct 24", "date_precision": "day", "issue": "2", "normalized_date": "2016-10-24", "pages": "169-185", "proceedings_title": null, "publisher": "", "title": "Developmental cell", "volume": "39", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "The Germ Cell Fate of Cynomolgus Monkeys Is Specified in the Nascent Amnion.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Neurofibrillar tangles caused by intracellular hyperphosphorylated tau inclusion and extracellular amyloid beta peptide deposition are hallmarks of Alzheimer's disease. Tau contains one or two cysteine residues in three or four repeats of the microtubule binding region following alternative splicing of exon 10, and formation of intermolecular cysteine disulfide bonds accelerates tau aggregation. 8-Nitroguanosine 3',5'-cyclic monophosphate (8-nitro-cGMP) acts as a novel second messenger of nitric oxide (NO) by covalently binding cGMP to cysteine residues by electrophilic properties, a process termed protein S-guanylation. Here we studied S-guanylation of tau and its effects on tau aggregation. 8-Nitro-cGMP exposure induced S-guanylation of tau both in vitro and in tau-overexpressed HEK293T cells. S-guanylated tau inhibited heparin-induced tau aggregation in a thioflavin T assay. Atomic force microscopy observations indicated that S-guanylated tau could not form tau granules and fibrils. Further biochemical analyses showed that S-guanylated tau was inhibited at the step of tau oligomer formation. In P301L tau-expressing Neuro2A cells, 8-nitro-cGMP treatment significantly reduced the amount of sarcosyl-insoluble tau. NO-linked chemical modification on cysteine residues of tau could block tau aggregation, and therefore, increasing 8-nitro-cGMP levels in the brain could become a potential therapeutic strategy for Alzheimer's disease.", "classifications": [ { "id": "Akaike", "label": "Group Akaike", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Jun", "last_name": "Yoshitake", "name": null }, { "creator_type": "author", "first_name": "Yoshiyuki", "last_name": "Soeda", "name": null }, { "creator_type": "author", "first_name": "Tomoaki", "last_name": "Ida", "name": null }, { "creator_type": "author", "first_name": "Akio", "last_name": "Sumioka", "name": null }, { "creator_type": "author", "first_name": "Misato", "last_name": "Yoshikawa", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Matsushita", "name": null }, { "creator_type": "author", "first_name": "Takaaki", "last_name": "Akaike", "name": null }, { "creator_type": "author", "first_name": "Akihiko", "last_name": "Takashima", "name": null } ], "identifiers": { "doi": { "normalized": "10.1074/jbc.m116.734350" }, "pmcid": { "normalized": "PMC5077206" }, "pmid": { "normalized": "27601475" } }, "mesh": [ { "descriptor": "Alzheimer Disease", "descriptor_ui": "D000544", "major_topic": false }, { "descriptor": "Cyclic GMP", "descriptor_ui": "D006152", "major_topic": false }, { "descriptor": "HEK293 Cells", "descriptor_ui": "D057809", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Nitric Oxide", "descriptor_ui": "D009569", "major_topic": false }, { "descriptor": "Protein Aggregates", "descriptor_ui": "D066329", "major_topic": true }, { "descriptor": "Protein Processing, Post-Translational", "descriptor_ui": "D011499", "major_topic": true }, { "descriptor": "tau Proteins", "descriptor_ui": "D016875", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016 Oct 21", "date_precision": "day", "issue": "43", "normalized_date": "2016-10-21", "pages": "22714-22720", "proceedings_title": null, "publisher": "", "title": "The Journal of biological chemistry", "volume": "291", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Modification of Tau by 8-Nitroguanosine 3',5'-Cyclic Monophosphate (8-Nitro-cGMP): EFFECTS OF NITRIC OXIDE-LINKED CHEMICAL MODIFICATION ON TAU AGGREGATION.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Dietary restriction (DR), such as calorie restriction (CR) or methionine (Met) restriction, extends the lifespan of diverse model organisms. Although studies have identified several metabolites that contribute to the beneficial effects of DR, the molecular mechanism underlying the key metabolites responsible for DR regimens is not fully understood. Here we show that stimulating S-adenosyl-l-methionine (AdoMet) synthesis extended the lifespan of the budding yeast Saccharomyces cerevisiae The AdoMet synthesis-mediated beneficial metabolic effects, which resulted from consuming both Met and ATP, mimicked CR. Indeed, stimulating AdoMet synthesis activated the universal energy-sensing regulator Snf1, which is the S. cerevisiae ortholog of AMP-activated protein kinase (AMPK), resulting in lifespan extension. Furthermore, our findings revealed that S-adenosyl-l-homocysteine contributed to longevity with a higher accumulation of AdoMet only under the severe CR (0.05% glucose) conditions. Thus, our data uncovered molecular links between Met metabolites and lifespan, suggesting a unique function of AdoMet as a reservoir of Met and ATP for cell survival.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Takafumi", "last_name": "Ogawa", "name": null }, { "creator_type": "author", "first_name": "Ryohei", "last_name": "Tsubakiyama", "name": null }, { "creator_type": "author", "first_name": "Muneyoshi", "last_name": "Kanai", "name": null }, { "creator_type": "author", "first_name": "Tetsuya", "last_name": "Koyama", "name": null }, { "creator_type": "author", "first_name": "Tsutomu", "last_name": "Fujii", "name": null }, { "creator_type": "author", "first_name": "Haruyuki", "last_name": "Iefuji", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Kazunori", "last_name": "Kume", "name": null }, { "creator_type": "author", "first_name": "Tokichi", "last_name": "Miyakawa", "name": null }, { "creator_type": "author", "first_name": "Dai", "last_name": "Hirata", "name": null }, { "creator_type": "author", "first_name": "Masaki", "last_name": "Mizunuma", "name": null } ], "identifiers": { "doi": { "normalized": "10.1073/pnas.1604047113" }, "pmcid": { "normalized": "PMC5081624" }, "pmid": { "normalized": "27698120" } }, "mesh": [ { "descriptor": "Adenosine Triphosphate", "descriptor_ui": "D000255", "major_topic": false }, { "descriptor": "AMP-Activated Protein Kinases", "descriptor_ui": "D055372", "major_topic": false }, { "descriptor": "Caloric Restriction", "descriptor_ui": "D031204", "major_topic": false }, { "descriptor": "Epistasis, Genetic", "descriptor_ui": "D004843", "major_topic": false }, { "descriptor": "Genes, Dominant", "descriptor_ui": "D005799", "major_topic": false }, { "descriptor": "Glucan 1,3-beta-Glucosidase", "descriptor_ui": "D043326", "major_topic": false }, { "descriptor": "Longevity", "descriptor_ui": "D008136", "major_topic": true }, { "descriptor": "Metabolic Networks and Pathways", "descriptor_ui": "D053858", "major_topic": false }, { "descriptor": "Methionine", "descriptor_ui": "D008715", "major_topic": false }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": false }, { "descriptor": "S-Adenosylmethionine", "descriptor_ui": "D012436", "major_topic": false }, { "descriptor": "Saccharomyces cerevisiae", "descriptor_ui": "D012441", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016 Oct 18", "date_precision": "day", "issue": "42", "normalized_date": "2016-10-18", "pages": "11913-11918", "proceedings_title": null, "publisher": "", "title": "Proceedings of the National Academy of Sciences of the United States of America", "volume": "113", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Stimulating S-adenosyl-l-methionine synthesis extends lifespan via activation of AMPK.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Acute myeloid leukemia (AML) is an aggressive cancer with a poor prognosis, for which mainstream treatments have not changed for decades. To identify additional therapeutic targets in AML, we optimize a genome-wide clustered regularly interspaced short palindromic repeats (CRISPR) screening platform and use it to identify genetic vulnerabilities in AML cells. We identify 492 AML-specific cell-essential genes, including several established therapeutic targets such as DOT1L, BCL2, and MEN1, and many other genes including clinically actionable candidates. We validate selected genes using genetic and pharmacological inhibition, and chose KAT2A as a candidate for downstream study. KAT2A inhibition demonstrated anti-AML activity by inducing myeloid differentiation and apoptosis, and suppressed the growth of primary human AMLs of diverse genotypes while sparing normal hemopoietic stem-progenitor cells. Our results propose that KAT2A inhibition should be investigated as a therapeutic strategy in AML and provide a large number of genetic vulnerabilities of this leukemia that can be pursued in downstream studies.", "classifications": [ { "id": "Yusa", "label": "Group Yusa", "parent": "Eiraku", "type": "group" }, { "id": "Eiraku", "label": "Team Eiraku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Konstantinos", "last_name": "Tzelepis", "name": null }, { "creator_type": "author", "first_name": "Hiroko", "last_name": "Koike-Yusa", "name": null }, { "creator_type": "author", "first_name": "Etienne", "last_name": "De Braekeleer", "name": null }, { "creator_type": "author", "first_name": "Yilong", "last_name": "Li", "name": null }, { "creator_type": "author", "first_name": "Emmanouil", "last_name": "Metzakopian", "name": null }, { "creator_type": "author", "first_name": "Oliver M.", "last_name": "Dovey", "name": null }, { "creator_type": "author", "first_name": "Annalisa", "last_name": "Mupo", "name": null }, { "creator_type": "author", "first_name": "Vera", "last_name": "Grinkevich", "name": null }, { "creator_type": "author", "first_name": "Meng", "last_name": "Li", "name": null }, { "creator_type": "author", "first_name": "Milena", "last_name": "Mazan", "name": null }, { "creator_type": "author", "first_name": "Malgorzata", "last_name": "Gozdecka", "name": null }, { "creator_type": "author", "first_name": "Shuhei", "last_name": "Ohnishi", "name": null }, { "creator_type": "author", "first_name": "Jonathan", "last_name": "Cooper", "name": null }, { "creator_type": "author", "first_name": "Miten", "last_name": "Patel", "name": null }, { "creator_type": "author", "first_name": "Thomas", "last_name": "McKerrell", "name": null }, { "creator_type": "author", "first_name": "Bin", "last_name": "Chen", "name": null }, { "creator_type": "author", "first_name": "Ana Filipa", "last_name": "Domingues", "name": null }, { "creator_type": "author", "first_name": "Paolo", "last_name": "Gallipoli", "name": null }, { "creator_type": "author", "first_name": "Sarah", "last_name": "Teichmann", "name": null }, { "creator_type": "author", "first_name": "Hannes", "last_name": "Ponstingl", "name": null }, { "creator_type": "author", "first_name": "Ultan", "last_name": "McDermott", "name": null }, { "creator_type": "author", "first_name": "Julio", "last_name": "Saez-Rodriguez", "name": null }, { "creator_type": "author", "first_name": "Brian J. P.", "last_name": "Huntly", "name": null }, { "creator_type": "author", "first_name": "Francesco", "last_name": "Iorio", "name": null }, { "creator_type": "author", "first_name": "Cristina", "last_name": "Pina", "name": null }, { "creator_type": "author", "first_name": "George S.", "last_name": "Vassiliou", "name": null }, { "creator_type": "author", "first_name": "Kosuke", "last_name": "Yusa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.celrep.2016.09.079" }, "pmcid": { "normalized": "PMC5081405" }, "pmid": { "normalized": "27760321" } }, "mesh": [ { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Apoptosis", "descriptor_ui": "D017209", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Cell Proliferation", "descriptor_ui": "D049109", "major_topic": false }, { "descriptor": "Clustered Regularly Interspaced Short Palindromic Repeats", "descriptor_ui": "D064112", "major_topic": false }, { "descriptor": "Genetic Testing", "descriptor_ui": "D005820", "major_topic": true }, { "descriptor": "Histone Acetyltransferases", "descriptor_ui": "D051548", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Leukemia, Myeloid, Acute", "descriptor_ui": "D015470", "major_topic": false }, { "descriptor": "Molecular Targeted Therapy", "descriptor_ui": "D058990", "major_topic": true }, { "descriptor": "p300-CBP-Associated Factor", "descriptor_ui": "D000099224", "major_topic": false }, { "descriptor": "Reproducibility of Results", "descriptor_ui": "D015203", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016 Oct 18", "date_precision": "day", "issue": "4", "normalized_date": "2016-10-18", "pages": "1193-1205", "proceedings_title": null, "publisher": "", "title": "Cell reports", "volume": "17", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "A CRISPR Dropout Screen Identifies Genetic Vulnerabilities and Therapeutic Targets in Acute Myeloid Leukemia.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Chronic fatigue syndrome (CFS) is a persistent and unexplained pathological state characterized by exertional and severely debilitating fatigue, with/without infectious or neuropsychiatric symptoms, lasting at least 6 consecutive months. Its pathogenesis remains incompletely understood. Here, we performed comprehensive metabolomic analyses of 133 plasma samples obtained from CFS patients and healthy controls to establish an objective diagnosis of CFS. CFS patients exhibited significant differences in intermediate metabolite concentrations in the tricarboxylic acid (TCA) and urea cycles. The combination of ornithine/citrulline and pyruvate/isocitrate ratios discriminated CFS patients from healthy controls, yielding area under the receiver operating characteristic curve values of 0.801 (95% confidential interval [CI]: 0.711-0.890, P < 0.0001) and 0.750 (95% CI: 0.584-0.916, P = 0.0069) for training (n = 93) and validation (n = 40) datasets, respectively. These findings provide compelling evidence that a clinical diagnostic tool could be developed for CFS based on the ratios of metabolites in plasma.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Emi", "last_name": "Yamano", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Sugimoto", "name": null }, { "creator_type": "author", "first_name": "Akiyoshi", "last_name": "Hirayama", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Kume", "name": null }, { "creator_type": "author", "first_name": "Masanori", "last_name": "Yamato", "name": null }, { "creator_type": "author", "first_name": "Guanghua", "last_name": "Jin", "name": null }, { "creator_type": "author", "first_name": "Seiki", "last_name": "Tajima", "name": null }, { "creator_type": "author", "first_name": "Nobuhito", "last_name": "Goda", "name": null }, { "creator_type": "author", "first_name": "Kazuhiro", "last_name": "Iwai", "name": null }, { "creator_type": "author", "first_name": "Sanae", "last_name": "Fukuda", "name": null }, { "creator_type": "author", "first_name": "Kouzi", "last_name": "Yamaguti", "name": null }, { "creator_type": "author", "first_name": "Hirohiko", "last_name": "Kuratsune", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Yasuyoshi", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Yosky", "last_name": "Kataoka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/srep34990" }, "pmcid": { "normalized": "PMC5057083" }, "pmid": { "normalized": "27725700" } }, "mesh": [ { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Asian People", "descriptor_ui": "D044466", "major_topic": false }, { "descriptor": "Biological Factors", "descriptor_ui": "D001685", "major_topic": false }, { "descriptor": "Biomarkers", "descriptor_ui": "D015415", "major_topic": false }, { "descriptor": "Fatigue Syndrome, Chronic", "descriptor_ui": "D015673", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Metabolic Networks and Pathways", "descriptor_ui": "D053858", "major_topic": false }, { "descriptor": "Metabolome", "descriptor_ui": "D055442", "major_topic": true }, { "descriptor": "Metabolomics", "descriptor_ui": "D055432", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Plasma", "descriptor_ui": "D010949", "major_topic": false }, { "descriptor": "ROC Curve", "descriptor_ui": "D012372", "major_topic": false }, { "descriptor": "Young Adult", "descriptor_ui": "D055815", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016 Oct 11", "date_precision": "day", "issue": "", "normalized_date": "2016-10-11", "pages": "34990", "proceedings_title": null, "publisher": "", "title": "Scientific reports", "volume": "6", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Index markers of chronic fatigue syndrome with dysfunction of TCA and urea cycles.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Isocitrate dehydrogenase 1 mutations drive human gliomagenesis, probably through neomorphic enzyme activity that produces D-2-hydroxyglutarate. To model this disease, we conditionally expressed Idh1(R132H) in the subventricular zone (SVZ) of the adult mouse brain. The mice developed hydrocephalus and grossly dilated lateral ventricles, with accumulation of 2-hydroxyglutarate and reduced alpha-ketoglutarate. Stem and transit amplifying/progenitor cell populations were expanded, and proliferation increased. Cells expressing SVZ markers infiltrated surrounding brain regions. SVZ cells also gave rise to proliferative subventricular nodules. DNA methylation was globally increased, while hydroxymethylation was decreased. Mutant SVZ cells overexpressed Wnt, cell-cycle and stem cell genes, and shared an expression signature with human gliomas. Idh1(R132H) mutation in the major adult neurogenic stem cell niche causes a phenotype resembling gliomagenesis.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Chiara", "last_name": "Bardella", "name": null }, { "creator_type": "author", "first_name": "Osama", "last_name": "Al-Dalahmah", "name": null }, { "creator_type": "author", "first_name": "Daniel", "last_name": "Krell", "name": null }, { "creator_type": "author", "first_name": "Pijus", "last_name": "Brazauskas", "name": null }, { "creator_type": "author", "first_name": "Khalid", "last_name": "Al-Qahtani", "name": null }, { "creator_type": "author", "first_name": "Marketa", "last_name": "Tomkova", "name": null }, { "creator_type": "author", "first_name": "Julie", "last_name": "Adam", "name": null }, { "creator_type": "author", "first_name": "Sebastien", "last_name": "Serres", "name": null }, { "creator_type": "author", "first_name": "Helen", "last_name": "Lockstone", "name": null }, { "creator_type": "author", "first_name": "Luke", "last_name": "Freeman-Mills", "name": null }, { "creator_type": "author", "first_name": "Inga", "last_name": "Pfeffer", "name": null }, { "creator_type": "author", "first_name": "Nicola", "last_name": "Sibson", "name": null }, { "creator_type": "author", "first_name": "Robert", "last_name": "Goldin", "name": null }, { "creator_type": "author", "first_name": "Benjamin", "last_name": "Schuster-Boeckler", "name": null }, { "creator_type": "author", "first_name": "Patrick J.", "last_name": "Pollard", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "James S.", "last_name": "McCullagh", "name": null }, { "creator_type": "author", "first_name": "Christopher J.", "last_name": "Schofield", "name": null }, { "creator_type": "author", "first_name": "Paul", "last_name": "Mulholland", "name": null }, { "creator_type": "author", "first_name": "Olaf", "last_name": "Ansorge", "name": null }, { "creator_type": "author", "first_name": "Skirmantas", "last_name": "Kriaucionis", "name": null }, { "creator_type": "author", "first_name": "Peter J.", "last_name": "Ratcliffe", "name": null }, { "creator_type": "author", "first_name": "Francis G.", "last_name": "Szele", "name": null }, { "creator_type": "author", "first_name": "Ian", "last_name": "Tomlinson", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.ccell.2016.08.017" }, "pmcid": { "normalized": "PMC5064912" }, "pmid": { "normalized": "27693047" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Brain Neoplasms", "descriptor_ui": "D001932", "major_topic": false }, { "descriptor": "DNA Methylation", "descriptor_ui": "D019175", "major_topic": false }, { "descriptor": "Glioma", "descriptor_ui": "D005910", "major_topic": false }, { "descriptor": "Isocitrate Dehydrogenase", "descriptor_ui": "D007521", "major_topic": false }, { "descriptor": "Lateral Ventricles", "descriptor_ui": "D020547", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Transgenic", "descriptor_ui": "D008822", "major_topic": false }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": false }, { "descriptor": "Neoplastic Stem Cells", "descriptor_ui": "D014411", "major_topic": false }, { "descriptor": "Stem Cell Niche", "descriptor_ui": "D055153", "major_topic": true }, { "descriptor": "Transcriptome", "descriptor_ui": "D059467", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016 Oct 10", "date_precision": "day", "issue": "4", "normalized_date": "2016-10-10", "pages": "578-594", "proceedings_title": null, "publisher": "", "title": "Cancer cell", "volume": "30", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Expression of Idh1(R132H) in the Murine Subventricular Zone Stem Cell Niche Recapitulates Features of Early Gliomagenesis.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Although abnormal metabolic regulation is a critical determinant of cancer cell behavior, it is still unclear how an altered balance between ATP production and consumption contributes to malignancy. Here we show that disruption of this energy balance efficiently suppresses aggressive malignant gliomas driven by mammalian target of rapamycin complex 1 (mTORC1) hyperactivation. In a mouse glioma model, mTORC1 hyperactivation induced by conditional Tsc1 deletion increased numbers of glioma-initiating cells (GICs) in vitro and in vivo Metabolic analysis revealed that mTORC1 hyperactivation enhanced mitochondrial biogenesis, as evidenced by elevations in oxygen consumption rate and ATP production. Inhibition of mitochondrial ATP synthetase was more effective in repressing sphere formation by Tsc1-deficient glioma cells than that by Tsc1-competent glioma cells, indicating a crucial function for mitochondrial bioenergetic capacity in GIC expansion. To translate this observation into the development of novel therapeutics targeting malignant gliomas, we screened drug libraries for small molecule compounds showing greater efficacy in inhibiting the proliferation/survival of Tsc1-deficient cells compared with controls. We identified several compounds able to preferentially inhibit mitochondrial activity, dramatically reducing ATP levels and blocking glioma sphere formation. In human patient-derived glioma cells, nigericin, which reportedly suppresses cancer stem cell properties, induced AMPK phosphorylation that was associated with mTORC1 inactivation and induction of autophagy and led to a marked decrease in sphere formation with loss of GIC marker expression. Furthermore, malignant characteristics of human glioma cells were markedly suppressed by nigericin treatment in vivo Thus, targeting mTORC1-driven processes, particularly those involved in maintaining a cancer cell's energy balance, may be an effective therapeutic strategy for glioma patients.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Ahmed M.", "last_name": "Hegazy", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Yamada", "name": null }, { "creator_type": "author", "first_name": "Masahiko", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Susumu", "last_name": "Kohno", "name": null }, { "creator_type": "author", "first_name": "Masaya", "last_name": "Ueno", "name": null }, { "creator_type": "author", "first_name": "Mohamed A. E.", "last_name": "Ali", "name": null }, { "creator_type": "author", "first_name": "Kumiko", "last_name": "Ohta", "name": null }, { "creator_type": "author", "first_name": "Yuko", "last_name": "Tadokoro", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Ino", "name": null }, { "creator_type": "author", "first_name": "Tomoki", "last_name": "Todo", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Chiaki", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Hirao", "name": null } ], "identifiers": { "doi": { "normalized": "10.1074/jbc.m116.734756" }, "pmcid": { "normalized": "PMC5076821" }, "pmid": { "normalized": "27519418" } }, "mesh": [ { "descriptor": "Adenosine Triphosphate", "descriptor_ui": "D000255", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Energy Metabolism", "descriptor_ui": "D004734", "major_topic": true }, { "descriptor": "Glioma", "descriptor_ui": "D005910", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mechanistic Target of Rapamycin Complex 1", "descriptor_ui": "D000076222", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred BALB C", "descriptor_ui": "D008807", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Mice, Nude", "descriptor_ui": "D008819", "major_topic": false }, { "descriptor": "Mitochondrial Proton-Translocating ATPases", "descriptor_ui": "D025261", "major_topic": false }, { "descriptor": "Multiprotein Complexes", "descriptor_ui": "D046912", "major_topic": false }, { "descriptor": "TOR Serine-Threonine Kinases", "descriptor_ui": "D058570", "major_topic": false }, { "descriptor": "Tuberous Sclerosis Complex 1 Protein", "descriptor_ui": "D000077004", "major_topic": false }, { "descriptor": "Tumor Suppressor Proteins", "descriptor_ui": "D025521", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016 Oct 7", "date_precision": "day", "issue": "41", "normalized_date": "2016-10-07", "pages": "21496-21509", "proceedings_title": null, "publisher": "", "title": "The Journal of biological chemistry", "volume": "291", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Therapeutic Strategy for Targeting Aggressive Malignant Gliomas by Disrupting Their Energy Balance.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The neural pathways underlying the respiratory variation dependent on vigilance states remain unsettled. In the present study, we examined the orexinergic innervation of Kolliker-Fuse nucleus (KFN) neurons sending their axons to the rostral ventral respiratory group (rVRG) and phrenic nucleus (PhN) as well as to the hypoglossal nucleus (HGN) by using a combined retrograde tracing and immunohistochemistry. After injection of cholera toxin B subunit (CTb) into the KFN, CTb-labeled neurons that are also immunoreactive for orexin (ORX) were found prominently in the perifornical and medial regions and additionally in the lateral region of the hypothalamic ORX field. After injection of fluorogold (FG) into the rVRG, PhN or HGN, we found an overlapping distribution of ORX-immunoreactive axon terminals and FG-labeled neurons in the KFN. Within the neuropil of the KFN, asymmetrical synaptic contacts were made between these terminals and neurons. We further demonstrated that many neurons labeled with FG injected into the rVRG, PhN, or HGN are immunoreactive for ORX receptor 2. Present data suggest that rVRG-, PhN- and HGN-projecting KFN neurons may be under the excitatory influence of the ORXergic neurons for the state-dependent regulation of respiration.", "classifications": [ { "id": "Yokota", "label": "Group Yokota", "parent": "Enomoto", "type": "group" }, { "id": "Enomoto", "label": "Team Enomoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Shigefumi", "last_name": "Yokota", "name": null }, { "creator_type": "author", "first_name": "Tatsuro", "last_name": "Oka", "name": null }, { "creator_type": "author", "first_name": "Hirohiko", "last_name": "Asano", "name": null }, { "creator_type": "author", "first_name": "Yukihiko", "last_name": "Yasui", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.brainres.2016.08.020" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "27544422" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Axons", "descriptor_ui": "D001369", "major_topic": false }, { "descriptor": "Cervical Cord", "descriptor_ui": "D066193", "major_topic": false }, { "descriptor": "Hypothalamus", "descriptor_ui": "D007031", "major_topic": false }, { "descriptor": "Immunohistochemistry", "descriptor_ui": "D007150", "major_topic": false }, { "descriptor": "Kolliker-Fuse Nucleus", "descriptor_ui": "D065836", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Medulla Oblongata", "descriptor_ui": "D008526", "major_topic": false }, { "descriptor": "Neural Pathways", "descriptor_ui": "D009434", "major_topic": false }, { "descriptor": "Neuroanatomical Tract-Tracing Techniques", "descriptor_ui": "D056347", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Orexin Receptors", "descriptor_ui": "D064446", "major_topic": false }, { "descriptor": "Orexins", "descriptor_ui": "D000068797", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Rats, Wistar", "descriptor_ui": "D017208", "major_topic": false }, { "descriptor": "Respiration", "descriptor_ui": "D012119", "major_topic": true }, { "descriptor": "Spinal Cord", "descriptor_ui": "D013116", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016 Oct 1", "date_precision": "day", "issue": "Pt A", "normalized_date": "2016-10-01", "pages": "512-523", "proceedings_title": null, "publisher": "", "title": "Brain research", "volume": "1648", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Orexinergic fibers are in contact with Kolliker-Fuse nucleus neurons projecting to the respiration-related nuclei in the medulla oblongata and spinal cord of the rat.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The fluorescence lifetime of the endogenous fluorophore of reduced nicotinamide adenine dinucleotide (NADH) in HeLa cells is affected by the application of nanosecond pulsed electric fields (nsPEFs). In this study, we found that after nsPEF application, the fluorescence lifetime became longer and then decreased in a stepwise manner upon further application, irrespective of the pulse width in the range of 10–50 ns. This application time dependence of the NADH fluorescence lifetime is very similar to the time-lapse dependence of the NADH fluorescence lifetime following the addition of an apoptosis inducer, staurosporine. These results, as well as the membrane swelling and blebbing after the application of nsPEFs, indicate that apoptosis is also induced by the application of nsPEFs in HeLa cells. In contrast to the lifetime, the fluorescence intensity remarkably depended on the pulse width of the applied nsPEF. When the pulse width was as large as 50 ns, the intensity monotonically increased and was distributed over the entire cell as the application duration became longer. As the pulse width of the applied electric field became smaller, the magnitude of the field-induced increase in NADH fluorescence intensity decreased; the intensity was reduced by the electric field when the pulse width was as small as 10 ns. These results suggest that the mechanism of electric-field-induced apoptosis depends on the pulse width of the applied nsPEF.", "classifications": [ { "id": "Nakabayashi", "label": "Group Nakabayashi", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Kamlesh", "last_name": "Awasthi", "name": null }, { "creator_type": "author", "first_name": "Takakazu", "last_name": "Nakabayashi", "name": null }, { "creator_type": "author", "first_name": "Nobuhiro", "last_name": "Ohta", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/acsomega.6b00090" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "30023482" } }, "mesh": [], "publication": { "conference_name": null, "date": "2016 Sep 30", "date_precision": "day", "issue": "3", "normalized_date": "2016-09-30", "pages": "396-406", "proceedings_title": null, "publisher": "", "title": "ACS Omega", "volume": "1", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Effects of Nanosecond Pulsed Electric Fields on the Intracellular Function of HeLa Cells As Revealed by NADH Autofluorescence Microscopy.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The gastrointestinal (GI) tract is innervated by intrinsic enteric neurons and by extrinsic efferent and afferent nerves. The enteric (intrinsic) nervous system (ENS) in most regions of the gut consists of two main ganglionated layers; myenteric and submucosal ganglia, containing numerous types of enteric neurons and glial cells. Axons arising from the ENS and from extrinsic neurons innervate most layers of the gut wall and regulate many gut functions. The majority of ENS cells are derived from vagal neural crest cells (NCCs), which proliferate, colonize the entire gut, and first populate the myenteric region. After gut colonization by vagal NCCs, the extrinsic nerve fibers reach the GI tract, and Schwann cell precursors (SCPs) enter the gut along the extrinsic nerves. Furthermore, a subpopulation of cells in myenteric ganglia undergoes a radial (inward) migration to form the submucosal plexus, and the intrinsic and extrinsic innervation to the mucosal region develops. Here, we focus on recent progress in understanding the developmental processes that occur after the gut is colonized by vagal ENS precursors, and provide an up-to-date overview of molecular mechanisms regulating the development of the intrinsic and extrinsic innervation of the GI tract.", "classifications": [ { "id": "Enomoto", "label": "Group Enomoto", "parent": "Enomoto", "type": "group" }, { "id": "Enomoto", "label": "Team Enomoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Toshihiro", "last_name": "Uesaka", "name": null }, { "creator_type": "author", "first_name": "Heather M.", "last_name": "Young", "name": null }, { "creator_type": "author", "first_name": "Vassilis", "last_name": "Pachnis", "name": null }, { "creator_type": "author", "first_name": "Hideki", "last_name": "Enomoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.ydbio.2016.04.016" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "27112528" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Movement", "descriptor_ui": "D002465", "major_topic": false }, { "descriptor": "Enteric Nervous System", "descriptor_ui": "D017615", "major_topic": true }, { "descriptor": "Gastrointestinal Tract", "descriptor_ui": "D041981", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Neural Crest", "descriptor_ui": "D009432", "major_topic": false }, { "descriptor": "Neurogenesis", "descriptor_ui": "D055495", "major_topic": false }, { "descriptor": "Neurons, Afferent", "descriptor_ui": "D009475", "major_topic": false }, { "descriptor": "Neurons, Efferent", "descriptor_ui": "D009476", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016 Sep 15", "date_precision": "day", "issue": "2", "normalized_date": "2016-09-15", "pages": "158-167", "proceedings_title": null, "publisher": "", "title": "Developmental biology", "volume": "417", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Development of the intrinsic and extrinsic innervation of the gut.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "8-Nitroguanosine 3',5'-cyclic monophosphate (8-nitro-cGMP) is a nitrated cGMP derivative formed in response to nitric oxide (NO) and reactive oxygen species (ROS). It can cause a post-translational modification (PTM) of protein thiols through cGMP adduction (protein S-guanylation). Accumulating evidence has suggested that, in mammals, S-guanylation of redox-sensor proteins may implicate in regulation of adaptive responses against ROS-associated oxidative stress. Occurrence as well as protein targets of S-guanylation in bacteria remained unknown, however. Here we demonstrated, for the first time, the endogenous occurrence of protein S-guanylation in Escherichia coli (E. coli). Western blotting using anti-S-guanylation antibody clearly showed that multiple proteins were S-guanylated in E. coli. Interestingly, some of those proteins were more intensely S-guanylated when bacteria were cultured under static culture condition than shaking culture condition. It has been known that E. coli is deficient of guanylate cyclase, an enzyme indispensable for 8-nitro-cGMP formation in mammals. We found that adenylate cyclase from E. coli potentially catalyzed 8-nitro-cGMP formation from its precursor 8-nitroguanosine 5'-triphosphate. More importantly, E. coli lacking adenylate cyclase showed significantly reduced formation of S-guanylated proteins. Our S-guanylation proteomics successfully identified S-guanylation protein targets in E. coli, including chaperons, ribosomal proteins, and enzymes which associate with protein synthesis, redox regulation and metabolism. Understanding of functional impacts for protein S-guanylation in bacterial signal transduction is necessary basis for development of potential chemotherapy and new diagnostic strategy for control of pathogenic bacterial infections.", "classifications": [ { "id": "Akaike", "label": "Group Akaike", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Hiroyasu", "last_name": "Tsutsuki", "name": null }, { "creator_type": "author", "first_name": "Minkyung", "last_name": "Jung", "name": null }, { "creator_type": "author", "first_name": "Tianli", "last_name": "Zhang", "name": null }, { "creator_type": "author", "first_name": "Katsuhiko", "last_name": "Ono", "name": null }, { "creator_type": "author", "first_name": "Tomoaki", "last_name": "Ida", "name": null }, { "creator_type": "author", "first_name": "Kohei", "last_name": "Kunieda", "name": null }, { "creator_type": "author", "first_name": "Hideshi", "last_name": "Ihara", "name": null }, { "creator_type": "author", "first_name": "Takaaki", "last_name": "Akaike", "name": null }, { "creator_type": "author", "first_name": "Tomohiro", "last_name": "Sawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.bbrc.2016.07.110" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "27473654" } }, "mesh": [ { "descriptor": "Adenylyl Cyclases", "descriptor_ui": "D000262", "major_topic": false }, { "descriptor": "Cyclic GMP", "descriptor_ui": "D006152", "major_topic": false }, { "descriptor": "Escherichia coli", "descriptor_ui": "D004926", "major_topic": false }, { "descriptor": "Escherichia coli Proteins", "descriptor_ui": "D029968", "major_topic": false }, { "descriptor": "Nitric Oxide", "descriptor_ui": "D009569", "major_topic": false }, { "descriptor": "Nitrite Reductases", "descriptor_ui": "D009572", "major_topic": false }, { "descriptor": "Oxidation-Reduction", "descriptor_ui": "D010084", "major_topic": false }, { "descriptor": "Oxidative Stress", "descriptor_ui": "D018384", "major_topic": false }, { "descriptor": "Protein Processing, Post-Translational", "descriptor_ui": "D011499", "major_topic": false }, { "descriptor": "Proteomics", "descriptor_ui": "D040901", "major_topic": false }, { "descriptor": "Reactive Oxygen Species", "descriptor_ui": "D017382", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016 Sep 9", "date_precision": "day", "issue": "1", "normalized_date": "2016-09-09", "pages": "7-11", "proceedings_title": null, "publisher": "", "title": "Biochemical and biophysical research communications", "volume": "478", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Endogenous occurrence of protein S-guanylation in Escherichia coli: Target identification and genetic regulation.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Most of the land plants generally have dorsoventrally flat leaves, maximizing the surface area of both upper (adaxial) side and lower (abaxial) side. The former is specialized for light capturing for photosynthesis and the latter is specialized for gas exchange. From findings of molecular genetics, it has been considered that the coupled dynamics between tissue morphogenesis and gene regulation for cell identity is responsible for making flat leaves. The hypothesis claims that a flat leaf is generated under two assumptions, (i) two mutually recessive groups of genes specify adaxial and abaxial sides of a leaf, (ii) cell divisions are induced at the limited region in the leaf margin where both of two groups are expressed. We examined the plausibility and possibility of this hypothesis from the dynamical point of view. We studied a mathematical model where two processes are coupled, tissue morphogenesis induced by cell division and deformation, and dynamics of gene regulations. From the analysis of the model we found that the classically believed hypothesis is not sufficient to generate flat leaves with high probability. We examined several different modifications and revision of the model. Then we found that a simple additional rule of polarized cell division facilitates flat leaf formation. The result of our analysis gives prediction of possible mechanism, which can be easily verified in experiments.", "classifications": [ { "id": "Mochizuki", "label": "Group Mochizuki", "parent": "Eiraku", "type": "group" }, { "id": "Eiraku", "label": "Team Eiraku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yoshinori", "last_name": "Hayakawa", "name": null }, { "creator_type": "author", "first_name": "Masashi", "last_name": "Tachikawa", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Mochizuki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.jtbi.2016.06.005" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "27287339" } }, "mesh": [ { "descriptor": "Cell Division", "descriptor_ui": "D002455", "major_topic": false }, { "descriptor": "Cell Polarity", "descriptor_ui": "D016764", "major_topic": false }, { "descriptor": "Gene Expression Regulation, Plant", "descriptor_ui": "D018506", "major_topic": true }, { "descriptor": "Genes, Plant", "descriptor_ui": "D017343", "major_topic": true }, { "descriptor": "Genes, Recessive", "descriptor_ui": "D005808", "major_topic": true }, { "descriptor": "Models, Biological", "descriptor_ui": "D008954", "major_topic": false }, { "descriptor": "Numerical Analysis, Computer-Assisted", "descriptor_ui": "D009716", "major_topic": false }, { "descriptor": "Plant Leaves", "descriptor_ui": "D018515", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016 Sep 7", "date_precision": "day", "issue": "", "normalized_date": "2016-09-07", "pages": "206-214", "proceedings_title": null, "publisher": "", "title": "Journal of theoretical biology", "volume": "404", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Flat leaf formation realized by cell-division control and mutual recessive gene regulation.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Interactions between dietary patterns and 2 beta-adrenergic receptor (ADRbeta) gene polymorphisms (ADRbeta2 Gln27Glu and ADRbeta3 Trp64Arg) were examined with regard to the effects on serum triglyceride levels. The cross-sectional study comprised 1720 men and women (aged 35-69 years) enrolled in the Japan Multi-Institutional Collaborative Cohort (J-MICC) Study. Genotyping was conducted using a multiplex polymerase chain reaction-based invader assay. We used 46 items from a validated short food frequency questionnaire and examined major dietary patterns by factor analysis. We identified four dietary patterns: healthy, Western, seafood and bread patterns. There was no significant association between any dietary pattern and serum triglyceride levels. After a separate genotype-based analysis, significant interactions between ADRbeta3 Trp64Arg genotype and the bread pattern (p for interaction = 0.01) were associated with serum triglyceride levels; specifically, after adjusting for confounding factors, Arg allele carriers with the bread pattern had lower serum triglycerides (p for trend = 0.01). However, the Trp/Trp homozygous subjects with the bread pattern showed no association with serum triglycerides (p for trend = 0.55). Interactions between other dietary patterns and ADRbeta polymorphisms were not significant for serum triglyceride levels. Our findings suggest that ADRbeta3 polymorphism modifies the effects of the bread pattern on triglyceride levels.", "classifications": [ { "id": "Tanaka", "label": "Group Tanaka", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Hinako", "last_name": "Nanri", "name": null }, { "creator_type": "author", "first_name": "Yuichiro", "last_name": "Nishida", "name": null }, { "creator_type": "author", "first_name": "Kazuyo", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Keitaro", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Mariko", "last_name": "Naito", "name": null }, { "creator_type": "author", "first_name": "Guang", "last_name": "Yin", "name": null }, { "creator_type": "author", "first_name": "Nobuyuki", "last_name": "Hamajima", "name": null }, { "creator_type": "author", "first_name": "Naoyuki", "last_name": "Takashima", "name": null }, { "creator_type": "author", "first_name": "Sadao", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Yora", "last_name": "Nindita", "name": null }, { "creator_type": "author", "first_name": "Michiko", "last_name": "Kohno", "name": null }, { "creator_type": "author", "first_name": "Hirokazu", "last_name": "Uemura", "name": null }, { "creator_type": "author", "first_name": "Teruhide", "last_name": "Koyama", "name": null }, { "creator_type": "author", "first_name": "Satoyo", "last_name": "Hosono", "name": null }, { "creator_type": "author", "first_name": "Haruo", "last_name": "Mikami", "name": null }, { "creator_type": "author", "first_name": "Michiaki", "last_name": "Kubo", "name": null }, { "creator_type": "author", "first_name": "Hideo", "last_name": "Tanaka", "name": null } ], "identifiers": { "doi": { "normalized": "10.3390/nu8090545" }, "pmcid": { "normalized": "PMC5037531" }, "pmid": { "normalized": "27608039" } }, "mesh": [ { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Alleles", "descriptor_ui": "D000483", "major_topic": false }, { "descriptor": "Cohort Studies", "descriptor_ui": "D015331", "major_topic": false }, { "descriptor": "Cross-Sectional Studies", "descriptor_ui": "D003430", "major_topic": false }, { "descriptor": "Diet", "descriptor_ui": "D004032", "major_topic": true }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Genotyping Techniques", "descriptor_ui": "D060005", "major_topic": false }, { "descriptor": "Heterozygote", "descriptor_ui": "D006579", "major_topic": false }, { "descriptor": "Homozygote", "descriptor_ui": "D006720", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Japan", "descriptor_ui": "D007564", "major_topic": false }, { "descriptor": "Linear Models", "descriptor_ui": "D016014", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Nutrition Assessment", "descriptor_ui": "D015596", "major_topic": false }, { "descriptor": "Polymorphism, Genetic", "descriptor_ui": "D011110", "major_topic": true }, { "descriptor": "Receptors, Adrenergic, beta-2", "descriptor_ui": "D018343", "major_topic": false }, { "descriptor": "Receptors, Adrenergic, beta-3", "descriptor_ui": "D022702", "major_topic": false }, { "descriptor": "Reproducibility of Results", "descriptor_ui": "D015203", "major_topic": false }, { "descriptor": "Surveys and Questionnaires", "descriptor_ui": "D011795", "major_topic": false }, { "descriptor": "Triglycerides", "descriptor_ui": "D014280", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016 Sep 6", "date_precision": "day", "issue": "9", "normalized_date": "2016-09-06", "pages": "", "proceedings_title": null, "publisher": "", "title": "Nutrients", "volume": "8", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Associations between Dietary Patterns, ADRbeta2 Gln27Glu and ADRbeta3 Trp64Arg with Regard to Serum Triglyceride Levels: J-MICC Study.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Macrophages play crucial roles in combatting infectious disease by promoting inflammation and phagocytosis. Angiopoietin-like protein 2 (ANGPTL2) is a secreted factor that induces tissue inflammation by attracting and activating macrophages to produce inflammatory cytokines in chronic inflammation-associated diseases such as obesity-associated metabolic syndrome, atherosclerosis, and rheumatoid arthritis. Here, we asked whether and how ANGPTL2 activates macrophages in the innate immune response. ANGPTL2 was predominantly expressed in proinflammatory mouse bone marrow-derived differentiated macrophages (GM-BMMs) following GM-CSF treatment relative to anti-inflammatory cells (M-BMMs) established by M-CSF treatment. Expression of the proinflammatory markers IL-1beta, IL-12p35, and IL-12p40 significantly decreased in GM-BMMs from Angptl2-deficient compared with wild-type (WT) mice, suggestive of attenuated proinflammatory activity. We also report that ANGPTL2 inflammatory signaling is transduced through integrin alpha5beta1 rather than through paired immunoglobulin-like receptor B. Interestingly, Angptl2-deficient mice were more susceptible to infection with Salmonella enterica serovar Typhimurium than were WT mice. Moreover, nitric oxide (NO) production by Angptl2-deficient GM-BMMs was significantly lower than in WT GM-BMMs. Collectively, our findings suggest that macrophage-derived ANGPTL2 promotes an innate immune response in those cells by enhancing proinflammatory activity and NO production required to fight infection.", "classifications": [ { "id": "Akaike", "label": "Group Akaike", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Masaki", "last_name": "Yugami", "name": null }, { "creator_type": "author", "first_name": "Haruki", "last_name": "Odagiri", "name": null }, { "creator_type": "author", "first_name": "Motoyoshi", "last_name": "Endo", "name": null }, { "creator_type": "author", "first_name": "Hiroyasu", "last_name": "Tsutsuki", "name": null }, { "creator_type": "author", "first_name": "Shigemoto", "last_name": "Fujii", "name": null }, { "creator_type": "author", "first_name": "Tsuyoshi", "last_name": "Kadomatsu", "name": null }, { "creator_type": "author", "first_name": "Tetsuro", "last_name": "Masuda", "name": null }, { "creator_type": "author", "first_name": "Keishi", "last_name": "Miyata", "name": null }, { "creator_type": "author", "first_name": "Kazutoyo", "last_name": "Terada", "name": null }, { "creator_type": "author", "first_name": "Hironori", "last_name": "Tanoue", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Jun", "last_name": "Morinaga", "name": null }, { "creator_type": "author", "first_name": "Haruki", "last_name": "Horiguchi", "name": null }, { "creator_type": "author", "first_name": "Taichi", "last_name": "Sugizaki", "name": null }, { "creator_type": "author", "first_name": "Takaaki", "last_name": "Akaike", "name": null }, { "creator_type": "author", "first_name": "Tomomi", "last_name": "Gotoh", "name": null }, { "creator_type": "author", "first_name": "Toshiyuki", "last_name": "Takai", "name": null }, { "creator_type": "author", "first_name": "Tomohiro", "last_name": "Sawa", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Mizuta", "name": null }, { "creator_type": "author", "first_name": "Yuichi", "last_name": "Oike", "name": null } ], "identifiers": { "doi": { "normalized": "10.1074/jbc.m116.720870" }, "pmcid": { "normalized": "PMC5009257" }, "pmid": { "normalized": "27402837" } }, "mesh": [ { "descriptor": "Angiopoietin-Like Protein 2", "descriptor_ui": "D000091302", "major_topic": false }, { "descriptor": "Angiopoietin-like Proteins", "descriptor_ui": "D000075802", "major_topic": false }, { "descriptor": "Angiopoietins", "descriptor_ui": "D042682", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Genetic Predisposition to Disease", "descriptor_ui": "D020022", "major_topic": true }, { "descriptor": "Immunity, Innate", "descriptor_ui": "D007113", "major_topic": true }, { "descriptor": "Macrophages", "descriptor_ui": "D008264", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Nitric Oxide", "descriptor_ui": "D009569", "major_topic": false }, { "descriptor": "Salmonella Infections", "descriptor_ui": "D012480", "major_topic": false }, { "descriptor": "Salmonella typhimurium", "descriptor_ui": "D012486", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016 Sep 2", "date_precision": "day", "issue": "36", "normalized_date": "2016-09-02", "pages": "18843-18852", "proceedings_title": null, "publisher": "", "title": "The Journal of biological chemistry", "volume": "291", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Mice Deficient in Angiopoietin-like Protein 2 (Angptl2) Gene Show Increased Susceptibility to Bacterial Infection Due to Attenuated Macrophage Activity.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The epiblast (EPI) is the origin of all somatic and germ cells in mammals, and of pluripotent stem cells in vitro. To explore the ontogeny of human and primate pluripotency, here we perform comprehensive single-cell RNA sequencing for pre- and post-implantation EPI development in cynomolgus monkeys (Macaca fascicularis). We show that after specification in the blastocysts, EPI from cynomolgus monkeys (cyEPI) undergoes major transcriptome changes on implantation. Thereafter, while generating gastrulating cells, cyEPI stably maintains its transcriptome over a week, retains a unique set of pluripotency genes and acquires properties for 'neuron differentiation'. Human and monkey pluripotent stem cells show the highest similarity to post-implantation late cyEPI, which, despite co-existing with gastrulating cells, bears characteristics of pre-gastrulating mouse EPI and epiblast-like cells in vitro. These findings not only reveal the divergence and coherence of EPI development, but also identify a developmental coordinate of the spectrum of pluripotency among key species, providing a basis for better regulation of human pluripotency in vitro.", "classifications": [ { "id": "Yamamoto", "label": "Group Yamamoto", "parent": "Toyoshima", "type": "group" }, { "id": "Toyoshima", "label": "Team Toyoshima", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Tomonori", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Ikuhiro", "last_name": "Okamoto", "name": null }, { "creator_type": "author", "first_name": "Kotaro", "last_name": "Sasaki", "name": null }, { "creator_type": "author", "first_name": "Yukihiro", "last_name": "Yabuta", "name": null }, { "creator_type": "author", "first_name": "Chizuru", "last_name": "Iwatani", "name": null }, { "creator_type": "author", "first_name": "Hideaki", "last_name": "Tsuchiya", "name": null }, { "creator_type": "author", "first_name": "Yasunari", "last_name": "Seita", "name": null }, { "creator_type": "author", "first_name": "Shinichiro", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Mitinori", "last_name": "Saitou", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/nature19096" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "27556940" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Blastocyst", "descriptor_ui": "D001755", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Embryo, Mammalian", "descriptor_ui": "D004622", "major_topic": false }, { "descriptor": "Embryonic Development", "descriptor_ui": "D047108", "major_topic": true }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Gastrulation", "descriptor_ui": "D054262", "major_topic": false }, { "descriptor": "Gene Expression Regulation, Developmental", "descriptor_ui": "D018507", "major_topic": false }, { "descriptor": "Germ Layers", "descriptor_ui": "D005855", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Macaca fascicularis", "descriptor_ui": "D008252", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Neural Stem Cells", "descriptor_ui": "D058953", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Pluripotent Stem Cells", "descriptor_ui": "D039904", "major_topic": false }, { "descriptor": "Sequence Analysis, RNA", "descriptor_ui": "D017423", "major_topic": false }, { "descriptor": "Single-Cell Analysis", "descriptor_ui": "D059010", "major_topic": false }, { "descriptor": "Species Specificity", "descriptor_ui": "D013045", "major_topic": false }, { "descriptor": "Transcriptome", "descriptor_ui": "D059467", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016 Sep 1", "date_precision": "day", "issue": "7618", "normalized_date": "2016-09-01", "pages": "57-62", "proceedings_title": null, "publisher": "", "title": "Nature", "volume": "537", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "A developmental coordinate of pluripotency among mice, monkeys and humans.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Notch-mediated lateral inhibition regulates binary cell fate choice, resulting in salt and pepper patterns during various developmental processes. However, how Notch signaling behaves in combination with other signaling systems remains elusive. The wave of differentiation in the Drosophila visual center or \"proneural wave\" accompanies Notch activity that is propagated without the formation of a salt and pepper pattern, implying that Notch does not form a feedback loop of lateral inhibition during this process. However, mathematical modeling and genetic analysis clearly showed that Notch-mediated lateral inhibition is implemented within the proneural wave. Because partial reduction in EGF signaling causes the formation of the salt and pepper pattern, it is most likely that EGF diffusion cancels salt and pepper pattern formation in silico and in vivo. Moreover, the combination of Notch-mediated lateral inhibition and EGF-mediated reaction diffusion enables a function of Notch signaling that regulates propagation of the wave of differentiation.", "classifications": [ { "id": "Nagayama", "label": "Group Nagayama", "parent": "Fujiwara", "type": "group" }, { "id": "Fujiwara", "label": "Team Fujiwara", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Makoto", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Tetsuo", "last_name": "Yasugi", "name": null }, { "creator_type": "author", "first_name": "Yoshiaki", "last_name": "Minami", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Miura", "name": null }, { "creator_type": "author", "first_name": "Masaharu", "last_name": "Nagayama", "name": null } ], "identifiers": { "doi": { "normalized": "10.1073/pnas.1602739113" }, "pmcid": { "normalized": "PMC5024646" }, "pmid": { "normalized": "27535937" } }, "mesh": [ { "descriptor": "Achaete-Scute Complex Genome Region", "descriptor_ui": "D058145", "major_topic": false }, { "descriptor": "Algorithms", "descriptor_ui": "D000465", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Animals, Genetically Modified", "descriptor_ui": "D030801", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Drosophila melanogaster", "descriptor_ui": "D004331", "major_topic": false }, { "descriptor": "Drosophila Proteins", "descriptor_ui": "D029721", "major_topic": false }, { "descriptor": "Epidermal Growth Factor", "descriptor_ui": "D004815", "major_topic": false }, { "descriptor": "Models, Neurological", "descriptor_ui": "D008959", "major_topic": false }, { "descriptor": "Neural Stem Cells", "descriptor_ui": "D058953", "major_topic": false }, { "descriptor": "Neuroepithelial Cells", "descriptor_ui": "D046569", "major_topic": false }, { "descriptor": "Neurogenesis", "descriptor_ui": "D055495", "major_topic": false }, { "descriptor": "Receptors, Notch", "descriptor_ui": "D051880", "major_topic": false }, { "descriptor": "Retina", "descriptor_ui": "D012160", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": true }, { "descriptor": "Superior Colliculi", "descriptor_ui": "D013477", "major_topic": false }, { "descriptor": "Visual Cortex", "descriptor_ui": "D014793", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016 Aug 30", "date_precision": "day", "issue": "35", "normalized_date": "2016-08-30", "pages": "E5153-5162", "proceedings_title": null, "publisher": "", "title": "Proceedings of the National Academy of Sciences of the United States of America", "volume": "113", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Notch-mediated lateral inhibition regulates proneural wave propagation when combined with EGF-mediated reaction diffusion.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Cell polarity arises through the spatial segregation of polarity regulators. PAR proteins are polarity regulators that localize asymmetrically to two opposing cortical domains. However, it is unclear how the spatially segregated PAR proteins interact to maintain their mutually exclusive partitioning. Here, single-molecule detection analysis in Caenorhabditis elegans embryos reveals that cortical PAR-2 diffuses only short distances, and, as a result, most PAR-2 molecules associate and dissociate from the cortex without crossing into the opposing domain. Our results show that cortical PAR-2 asymmetry is maintained by the local exchange reactions that occur at the cortical-cytoplasmic boundary. Additionally, we demonstrate that local exchange reactions are sufficient to maintain cortical asymmetry in a parameter-free mathematical model. These findings suggest that anterior and posterior PAR proteins primarily interact through the cytoplasmic pool and not via cortical diffusion.", "classifications": [ { "id": "Kobayashi", "label": "Group Kobayashi", "parent": "Wakamoto", "type": "group" }, { "id": "Wakamoto", "label": "Team Wakamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yukinobu", "last_name": "Arata", "name": null }, { "creator_type": "author", "first_name": "Michio", "last_name": "Hiroshima", "name": null }, { "creator_type": "author", "first_name": "Chan-Gi", "last_name": "Pack", "name": null }, { "creator_type": "author", "first_name": "Ravikrishna", "last_name": "Ramanujam", "name": null }, { "creator_type": "author", "first_name": "Fumio", "last_name": "Motegi", "name": null }, { "creator_type": "author", "first_name": "Kenichi", "last_name": "Nakazato", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Shindo", "name": null }, { "creator_type": "author", "first_name": "Paul W.", "last_name": "Wiseman", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Sawa", "name": null }, { "creator_type": "author", "first_name": "Tetsuya J.", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Hugo B.", "last_name": "Brandao", "name": null }, { "creator_type": "author", "first_name": "Tatsuo", "last_name": "Shibata", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Sako", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.celrep.2016.07.047" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "27524610" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Caenorhabditis elegans", "descriptor_ui": "D017173", "major_topic": false }, { "descriptor": "Caenorhabditis elegans Proteins", "descriptor_ui": "D029742", "major_topic": false }, { "descriptor": "Cell Compartmentation", "descriptor_ui": "D002451", "major_topic": false }, { "descriptor": "Cell Polarity", "descriptor_ui": "D016764", "major_topic": false }, { "descriptor": "Cytoplasm", "descriptor_ui": "D003593", "major_topic": false }, { "descriptor": "Embryo, Nonmammalian", "descriptor_ui": "D004625", "major_topic": false }, { "descriptor": "Gene Expression Regulation", "descriptor_ui": "D005786", "major_topic": false }, { "descriptor": "Kinetics", "descriptor_ui": "D007700", "major_topic": false }, { "descriptor": "Models, Statistical", "descriptor_ui": "D015233", "major_topic": true }, { "descriptor": "Phosphorylation", "descriptor_ui": "D010766", "major_topic": false }, { "descriptor": "Protein Transport", "descriptor_ui": "D021381", "major_topic": false }, { "descriptor": "Single Molecule Imaging", "descriptor_ui": "D000072760", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016 Aug 23", "date_precision": "day", "issue": "8", "normalized_date": "2016-08-23", "pages": "2156-2168", "proceedings_title": null, "publisher": "", "title": "Cell reports", "volume": "16", "year": 2016 }, "ssbd": { "database": [ "ssbd-database-000037" ], "repository": [ "ssbd-repos-000037" ] }, "title": "Cortical Polarity of the RING Protein PAR-2 Is Maintained by Exchange Rate Kinetics at the Cortical-Cytoplasmic Boundary.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The objective of this study was to explore salivary metabolite biomarkers by profiling both saliva and tumor tissue samples for oral cancer screening. Paired tumor and control tissues were obtained from oral cancer patients and whole unstimulated saliva samples were collected from patients and healthy controls. The comprehensive metabolomic analysis for profiling hydrophilic metabolites was conducted using capillary electrophoresis time-of-flight mass spectrometry. In total, 85 and 45 metabolites showed significant differences between tumor and matched control samples, and between salivary samples from oral cancer and controls, respectively (P < 0.05 correlated by false discovery rate); 17 metabolites showed consistent differences in both saliva and tissue-based comparisons. Of these, a combination of only two biomarkers yielded a high area under receiver operating characteristic curves (0.827; 95% confidence interval, 0.726-0.928, P < 0.0001) for discriminating oral cancers from controls. Various validation tests confirmed its high generalization ability. The demonstrated approach, integrating both saliva and tumor tissue metabolomics, helps eliminate pseudo-molecules that are coincidentally different between oral cancers and controls. These combined salivary metabolites could be the basis of a clinically feasible method of non-invasive oral cancer screening.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Shigeo", "last_name": "Ishikawa", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Sugimoto", "name": null }, { "creator_type": "author", "first_name": "Kenichiro", "last_name": "Kitabatake", "name": null }, { "creator_type": "author", "first_name": "Ayako", "last_name": "Sugano", "name": null }, { "creator_type": "author", "first_name": "Marina", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Miku", "last_name": "Kaneko", "name": null }, { "creator_type": "author", "first_name": "Sana", "last_name": "Ota", "name": null }, { "creator_type": "author", "first_name": "Kana", "last_name": "Hiwatari", "name": null }, { "creator_type": "author", "first_name": "Ayame", "last_name": "Enomoto", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Masaru", "last_name": "Tomita", "name": null }, { "creator_type": "author", "first_name": "Mitsuyoshi", "last_name": "Iino", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/srep31520" }, "pmcid": { "normalized": "PMC4990923" }, "pmid": { "normalized": "27539254" } }, "mesh": [ { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Aged, 80 and over", "descriptor_ui": "D000369", "major_topic": false }, { "descriptor": "Biomarkers, Tumor", "descriptor_ui": "D014408", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Metabolomics", "descriptor_ui": "D055432", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Mouth Neoplasms", "descriptor_ui": "D009062", "major_topic": false }, { "descriptor": "Saliva", "descriptor_ui": "D012463", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016 Aug 19", "date_precision": "day", "issue": "", "normalized_date": "2016-08-19", "pages": "31520", "proceedings_title": null, "publisher": "", "title": "Scientific reports", "volume": "6", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Identification of salivary metabolomic biomarkers for oral cancer screening.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Dictyostelium morphogenesis requires the tip, which acts as an organizer and conducts orchestrated cell movement and cell differentiation. At the slug stage the tip region contains prestalk A (pstA) cells, which are usually recognized by their expression of reporter constructs that utilize a fragment of the promoter of the ecmA gene. Here, using the promoter region of the o-methyl transferase 12 gene (omt12) to drive reporter expression, we demonstrate the presence, also within the pstA region, of a novel prestalk cell subtype: the pstV(A) cells. Surprisingly, a sub-population of the vegetative cells express a pstV(A): GFP marker and, sort out to the tip, both when developing alone and when co-developed with an excess of unmarked cells. The development of such a purified GFP-marked population is greatly accelerated: by precocious cell aggregation and tip formation with accompanying precocious elevation of developmental gene transcription. We therefore suggest that the tip contains at least two prestalk cell subtypes: the developmentally-specified pstA cells and the lineage-primed pstV(A) cells. It is presumably the pstV(A) cells that play the dominant role in morphogenesis during the earlier stages of development. The basis for the lineage priming is, however, unclear because we can find no correlation between pstV(A) differentiation and nutrient status during growth or cell cycle position at the time of starvation, the two known determinants of probable cell fate.", "classifications": [ { "id": "Sawai", "label": "Group Sawai", "parent": "Sawai", "type": "group" }, { "id": "Sawai", "label": "Team Sawai", "type": "team" } ], "creators": [ { "creator_type": "contributor", "first_name": "Satoshi", "last_name": "Kuwana", "name": null }, { "creator_type": "contributor", "first_name": "Hiroshi", "last_name": "Senoo", "name": null }, { "creator_type": "contributor", "first_name": "Satoshi", "last_name": "Sawai", "name": null }, { "creator_type": "contributor", "first_name": "Masashi", "last_name": "Fukuzawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.ydbio.2016.06.032" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "27373689" } }, "mesh": [ { "descriptor": "Cell Aggregation", "descriptor_ui": "D002449", "major_topic": false }, { "descriptor": "Cell Lineage", "descriptor_ui": "D019070", "major_topic": false }, { "descriptor": "Cell Movement", "descriptor_ui": "D002465", "major_topic": false }, { "descriptor": "Dictyostelium", "descriptor_ui": "D004023", "major_topic": false }, { "descriptor": "Flow Cytometry", "descriptor_ui": "D005434", "major_topic": false }, { "descriptor": "Genes, Protozoan", "descriptor_ui": "D017125", "major_topic": false }, { "descriptor": "Genes, Reporter", "descriptor_ui": "D017930", "major_topic": false }, { "descriptor": "Green Fluorescent Proteins", "descriptor_ui": "D049452", "major_topic": false }, { "descriptor": "Microscopy, Confocal", "descriptor_ui": "D018613", "major_topic": false }, { "descriptor": "Microscopy, Fluorescence", "descriptor_ui": "D008856", "major_topic": false }, { "descriptor": "Morphogenesis", "descriptor_ui": "D009024", "major_topic": false }, { "descriptor": "Promoter Regions, Genetic", "descriptor_ui": "D011401", "major_topic": false }, { "descriptor": "Protein O-Methyltransferase", "descriptor_ui": "D011497", "major_topic": false }, { "descriptor": "Protozoan Proteins", "descriptor_ui": "D015800", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016 Aug 15", "date_precision": "day", "issue": "2", "normalized_date": "2016-08-15", "pages": "286-299", "proceedings_title": null, "publisher": "", "title": "Developmental biology", "volume": "416", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "A novel, lineage-primed prestalk cell subtype involved in the morphogenesis of D. discoideum.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Hematopoietic stem cells (HSCs) maintain quiescence by activating specific metabolic pathways, including glycolysis. We do not yet have a clear understanding of how this metabolic activity changes during stress hematopoiesis, such as bone marrow transplantation. Here, we report a critical role for the p38MAPK family isoform p38alpha in initiating hematopoietic stem and progenitor cell (HSPC) proliferation during stress hematopoiesis in mice. We found that p38MAPK is immediately phosphorylated in HSPCs after a hematological stress, preceding increased HSPC cycling. Conditional deletion of p38alpha led to defective recovery from hematological stress and a delay in initiation of HSPC proliferation. Mechanistically, p38alpha signaling increases expression of inosine-5'-monophosphate dehydrogenase 2 in HSPCs, leading to altered levels of amino acids and purine-related metabolites and changes in cell-cycle progression in vitro and in vivo. Our studies have therefore uncovered a p38alpha-mediated pathway that alters HSPC metabolism to respond to stress and promote recovery.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Daiki", "last_name": "Karigane", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Takayuki", "last_name": "Morikawa", "name": null }, { "creator_type": "author", "first_name": "Yukako", "last_name": "Ootomo", "name": null }, { "creator_type": "author", "first_name": "Mashito", "last_name": "Sakai", "name": null }, { "creator_type": "author", "first_name": "Go", "last_name": "Nagamatsu", "name": null }, { "creator_type": "author", "first_name": "Yoshiaki", "last_name": "Kubota", "name": null }, { "creator_type": "author", "first_name": "Nobuhito", "last_name": "Goda", "name": null }, { "creator_type": "author", "first_name": "Michihiro", "last_name": "Matsumoto", "name": null }, { "creator_type": "author", "first_name": "Emi K.", "last_name": "Nishimura", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Kinya", "last_name": "Otsu", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Suematsu", "name": null }, { "creator_type": "author", "first_name": "Shinichiro", "last_name": "Okamoto", "name": null }, { "creator_type": "author", "first_name": "Toshio", "last_name": "Suda", "name": null }, { "creator_type": "author", "first_name": "Keiyo", "last_name": "Takubo", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.stem.2016.05.013" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "27345838" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Apoptosis", "descriptor_ui": "D017209", "major_topic": false }, { "descriptor": "Cell Cycle", "descriptor_ui": "D002453", "major_topic": true }, { "descriptor": "Cell Proliferation", "descriptor_ui": "D049109", "major_topic": false }, { "descriptor": "Enzyme Activation", "descriptor_ui": "D004789", "major_topic": false }, { "descriptor": "Hematopoiesis", "descriptor_ui": "D006410", "major_topic": false }, { "descriptor": "Hematopoietic Stem Cell Transplantation", "descriptor_ui": "D018380", "major_topic": false }, { "descriptor": "Hematopoietic Stem Cells", "descriptor_ui": "D006412", "major_topic": false }, { "descriptor": "IMP Dehydrogenase", "descriptor_ui": "D007168", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Microphthalmia-Associated Transcription Factor", "descriptor_ui": "D051739", "major_topic": false }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": false }, { "descriptor": "p38 Mitogen-Activated Protein Kinases", "descriptor_ui": "D048051", "major_topic": false }, { "descriptor": "Phenotype", "descriptor_ui": "D010641", "major_topic": false }, { "descriptor": "Purines", "descriptor_ui": "D011687", "major_topic": false }, { "descriptor": "Reactive Oxygen Species", "descriptor_ui": "D017382", "major_topic": false }, { "descriptor": "Stress, Physiological", "descriptor_ui": "D013312", "major_topic": true } ], "publication": { "conference_name": null, "date": "2016 Aug 4", "date_precision": "day", "issue": "2", "normalized_date": "2016-08-04", "pages": "192-204", "proceedings_title": null, "publisher": "", "title": "Cell stem cell", "volume": "19", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "p38alpha Activates Purine Metabolism to Initiate Hematopoietic Stem/Progenitor Cell Cycling in Response to Stress.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "In living cells, chemical reactions are connected by sharing their products and substrates, and form complex networks, e.g., metabolic pathways. Here we developed a theory to predict the sensitivity, i.e., the responses of concentrations and fluxes to perturbations of enzymes, from network structure alone. Nonzero response patterns turn out to exhibit two characteristic features, localization and hierarchy. We present a general theorem connecting sensitivity with network topology that explains these characteristic patterns. Our results imply that network topology is an origin of biological robustness. Finally, we suggest a strategy to determine real networks from experimental measurements.", "classifications": [ { "id": "Mochizuki", "label": "Group Mochizuki", "parent": "Eiraku", "type": "group" }, { "id": "Eiraku", "label": "Team Eiraku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Takashi", "last_name": "Okada", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Mochizuki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1103/physrevlett.117.048101" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "27494502" } }, "mesh": [ { "descriptor": "Computer Simulation", "descriptor_ui": "D003198", "major_topic": false }, { "descriptor": "Metabolic Networks and Pathways", "descriptor_ui": "D053858", "major_topic": true }, { "descriptor": "Models, Biological", "descriptor_ui": "D008954", "major_topic": true } ], "publication": { "conference_name": null, "date": "2016 Jul 22", "date_precision": "day", "issue": "4", "normalized_date": "2016-07-22", "pages": "048101", "proceedings_title": null, "publisher": "", "title": "Physical review letters", "volume": "117", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Law of Localization in Chemical Reaction Networks.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "AIM: To clarify the characteristics of metabolite profiles in virus-related hepatocellular carcinoma (HCC) patients using serum metabolome analysis.METHODS: The serum levels of low-molecular-weight metabolites in 68 patients with HCC were quantified using capillary electrophoresis chromatography and mass spectrometry. Thirty and 38 of the patients suffered from hepatitis B virus-related HCC (HCC-B) and hepatitis C virus-related HCC (HCC-C), respectively.RESULTS: The main metabolites characteristic of HCC were those associated with glutathione metabolism, notably 13 γ-glutamyl peptides, which are by-products of glutathione induction. Two major profiles, i.e., concentration patterns, of metabolites were identified in HCC patients, and these were classified into two groups: an HCC-B group and an HCC-C group including some of the HCC-B cases. The receiver operating characteristic curve for the multiple logistic regression model discriminating HCC-B from HCC-C incorporating the concentrations of glutamic acid, methionine and γ-glutamyl-glycine-glycine showed a highly significant area under the curve value of 0.94 (95%CI: 0.89-1.0, P < 0.0001).CONCLUSION: The serum levels of γ-glutamyl peptides, as well as their concentration patterns, contribute to the development of potential biomarkers for virus-related HCC. The difference in metabolite profiles between HCC-B and HCC-C may reflect the respective metabolic reactions that underlie the different pathogeneses of these two types of HCC.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Takafumi", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Sugimoto", "name": null }, { "creator_type": "author", "first_name": "Kazuo", "last_name": "Okumoto", "name": null }, { "creator_type": "author", "first_name": "Hiroaki", "last_name": "Haga", "name": null }, { "creator_type": "author", "first_name": "Tomohiro", "last_name": "Katsumi", "name": null }, { "creator_type": "author", "first_name": "Kei", "last_name": "Mizuno", "name": null }, { "creator_type": "author", "first_name": "Taketo", "last_name": "Nishina", "name": null }, { "creator_type": "author", "first_name": "Sonoko", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Kaori", "last_name": "Igarashi", "name": null }, { "creator_type": "author", "first_name": "Hiroko", "last_name": "Maki", "name": null }, { "creator_type": "author", "first_name": "Masaru", "last_name": "Tomita", "name": null }, { "creator_type": "author", "first_name": "Yoshiyuki", "last_name": "Ueno", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null } ], "identifiers": { "doi": { "normalized": "10.3748/wjg.v22.i27.6224" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "27468212" } }, "mesh": [ { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Aged, 80 and over", "descriptor_ui": "D000369", "major_topic": false }, { "descriptor": "Capillary Electrochromatography", "descriptor_ui": "D053801", "major_topic": false }, { "descriptor": "Carcinoma, Hepatocellular", "descriptor_ui": "D006528", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Glutathione", "descriptor_ui": "D005978", "major_topic": false }, { "descriptor": "Hepatitis B, Chronic", "descriptor_ui": "D019694", "major_topic": false }, { "descriptor": "Hepatitis C, Chronic", "descriptor_ui": "D019698", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Liver Neoplasms", "descriptor_ui": "D008113", "major_topic": false }, { "descriptor": "Logistic Models", "descriptor_ui": "D016015", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mass Spectrometry", "descriptor_ui": "D013058", "major_topic": false }, { "descriptor": "Metabolome", "descriptor_ui": "D055442", "major_topic": true }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Oxidative Stress", "descriptor_ui": "D018384", "major_topic": false }, { "descriptor": "ROC Curve", "descriptor_ui": "D012372", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016 Jul 21", "date_precision": "day", "issue": "27", "normalized_date": "2016-07-21", "pages": "6224-6234", "proceedings_title": null, "publisher": "", "title": "World Journal of Gastroenterology", "volume": "22", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Serum metabolome profiles characterized by patients with hepatocellular carcinoma associated with hepatitis B and C.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "An efficient perfluoroalkylation of unactivated alkenes with perfluoro acid anhydrides was developed. Copper salts play a crucial role as a catalyst to achieve allylic perfluoroalkylation with the in situ generated bis(perfluoroacyl) peroxides. Furthermore, carboperfluoroalkylation of alkene bearing an aromatic ring at an appropriate position on the carbon side chain was found to proceed under metal-free conditions to afford carbocycles or heterocycles bearing a perfluoroalkyl group. This method, which makes use of readily available perfluoroalkyl sources, offers a convenient and powerful tool for introducing a perfluoroalkyl group onto an sp(3) carbon to construct synthetically useful skeletons.", "classifications": [ { "id": "Sodeoka", "label": "Group Sodeoka", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Shintaro", "last_name": "Kawamura", "name": null }, { "creator_type": "author", "first_name": "Mikiko", "last_name": "Sodeoka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/anie.201604127" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "27254318" } }, "mesh": [], "publication": { "conference_name": null, "date": "2016 Jul 18", "date_precision": "day", "issue": "30", "normalized_date": "2016-07-18", "pages": "8740-8743", "proceedings_title": null, "publisher": "", "title": "Angewandte Chemie (International ed. in English)", "volume": "55", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Perfluoroalkylation of Unactivated Alkenes with Acid Anhydrides as the Perfluoroalkyl Source.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Cardiovascular complications are the leading cause of death in autosomal dominant polycystic kidney disease (ADPKD), and intracranial aneurysm (ICA) causing subarachnoid hemorrhage is among the most serious complications. The diagnostic and therapeutic strategies for ICAs in ADPKD have not been fully established. We here generated induced pluripotent stem cells (iPSCs) from seven ADPKD patients, including four with ICAs. The vascular cells differentiated from ADPKD-iPSCs showed altered Ca(2+) entry and gene expression profiles compared with those of iPSCs from non-ADPKD subjects. We found that the expression level of a metalloenzyme gene, matrix metalloproteinase (MMP) 1, was specifically elevated in iPSC-derived endothelia from ADPKD patients with ICAs. Furthermore, we confirmed the correlation between the serum MMP1 levels and the development of ICAs in 354 ADPKD patients, indicating that high serum MMP1 levels may be a novel risk factor. These results suggest that cellular disease models with ADPKD-specific iPSCs can be used to study the disease mechanisms and to identify novel disease-related molecules or risk factors.", "classifications": [ { "id": "Yamamoto", "label": "Group Yamamoto", "parent": "Toyoshima", "type": "group" }, { "id": "Toyoshima", "label": "Team Toyoshima", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Tomonaga", "last_name": "Ameku", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Taura", "name": null }, { "creator_type": "author", "first_name": "Masakatsu", "last_name": "Sone", "name": null }, { "creator_type": "author", "first_name": "Tomohiro", "last_name": "Numata", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Fumihiko", "last_name": "Shiota", "name": null }, { "creator_type": "author", "first_name": "Taro", "last_name": "Toyoda", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Matsui", "name": null }, { "creator_type": "author", "first_name": "Toshikazu", "last_name": "Araoka", "name": null }, { "creator_type": "author", "first_name": "Tetsuhiko", "last_name": "Yasuno", "name": null }, { "creator_type": "author", "first_name": "Shin-Ichi", "last_name": "Mae", "name": null }, { "creator_type": "author", "first_name": "Hatasu", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Naoya", "last_name": "Kondo", "name": null }, { "creator_type": "author", "first_name": "Fumiyo", "last_name": "Kitaoka", "name": null }, { "creator_type": "author", "first_name": "Naoki", "last_name": "Amano", "name": null }, { "creator_type": "author", "first_name": "Sayaka", "last_name": "Arai", "name": null }, { "creator_type": "author", "first_name": "Tomoko", "last_name": "Ichisaka", "name": null }, { "creator_type": "author", "first_name": "Norio", "last_name": "Matsuura", "name": null }, { "creator_type": "author", "first_name": "Sumiko", "last_name": "Inoue", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Kazutoshi", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Isao", "last_name": "Asaka", "name": null }, { "creator_type": "author", "first_name": "Yasuhiro", "last_name": "Yamada", "name": null }, { "creator_type": "author", "first_name": "Yoshifumi", "last_name": "Ubara", "name": null }, { "creator_type": "author", "first_name": "Eri", "last_name": "Muso", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Fukatsu", "name": null }, { "creator_type": "author", "first_name": "Akira", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Yasunori", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Tatsutoshi", "last_name": "Nakahata", "name": null }, { "creator_type": "author", "first_name": "Yasuo", "last_name": "Mori", "name": null }, { "creator_type": "author", "first_name": "Akio", "last_name": "Koizumi", "name": null }, { "creator_type": "author", "first_name": "Kazuwa", "last_name": "Nakao", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Yamanaka", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Osafune", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/srep30013" }, "pmcid": { "normalized": "PMC4945931" }, "pmid": { "normalized": "27418197" } }, "mesh": [ { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Biomarkers", "descriptor_ui": "D015415", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "DNA Methylation", "descriptor_ui": "D019175", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Induced Pluripotent Stem Cells", "descriptor_ui": "D057026", "major_topic": false }, { "descriptor": "Intracranial Aneurysm", "descriptor_ui": "D002532", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Matrix Metalloproteinase 1", "descriptor_ui": "D020781", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred NOD", "descriptor_ui": "D016688", "major_topic": false }, { "descriptor": "Mice, SCID", "descriptor_ui": "D016513", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Polycystic Kidney, Autosomal Dominant", "descriptor_ui": "D016891", "major_topic": false }, { "descriptor": "Risk Factors", "descriptor_ui": "D012307", "major_topic": false }, { "descriptor": "Subarachnoid Hemorrhage", "descriptor_ui": "D013345", "major_topic": false }, { "descriptor": "TRPP Cation Channels", "descriptor_ui": "D050396", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016 Jul 15", "date_precision": "day", "issue": "", "normalized_date": "2016-07-15", "pages": "30013", "proceedings_title": null, "publisher": "", "title": "Scientific reports", "volume": "6", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Identification of MMP1 as a novel risk factor for intracranial aneurysms in ADPKD using iPSC models.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Amyloid β-protein (Aβ42) oligomerization is an early event in Alzheimer's disease (AD). Current diagnostic methods using sequence-specific antibodies against less toxic fibrillar and monomeric Aβ42 run the risk of overdiagnosis. Hence, conformation-specific antibodies against neurotoxic Aβ42 oligomers have garnered much attention for developing more accurate diagnostics. Antibody 24B3, highly specific for the toxic Aβ42 conformer that has a turn at Glu22 and Asp23, recognizes a putative Aβ42 dimer, which forms stable and neurotoxic oligomers more potently than the monomer. 24B3 significantly rescues Aβ42-induced neurotoxicity, whereas sequence-specific antibodies such as 4G8 and 82E1, which recognizes the N-terminus, do not. The ratio of toxic to total Aβ42 in the cerebrospinal fluid of AD patients is significantly higher than in control subjects as measured by sandwich ELISA using antibodies 24B3 and 82E1. Thus, 24B3 may be useful for AD diagnosis and therapy.", "classifications": [ { "id": "Suzuki", "label": "Group Suzuki", "parent": "Takekawa", "type": "group" }, { "id": "Takekawa", "label": "Team Takekawa", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Kazuma", "last_name": "Murakami", "name": null }, { "creator_type": "author", "first_name": "Maki", "last_name": "Tokuda", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Yumi", "last_name": "Irie", "name": null }, { "creator_type": "author", "first_name": "Mizuho", "last_name": "Hanaki", "name": null }, { "creator_type": "author", "first_name": "Naotaka", "last_name": "Izuo", "name": null }, { "creator_type": "author", "first_name": "Yoko", "last_name": "Monobe", "name": null }, { "creator_type": "author", "first_name": "Ken-Ichi", "last_name": "Akagi", "name": null }, { "creator_type": "author", "first_name": "Ryotaro", "last_name": "Ishii", "name": null }, { "creator_type": "author", "first_name": "Harutsugu", "last_name": "Tatebe", "name": null }, { "creator_type": "author", "first_name": "Takahiko", "last_name": "Tokuda", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Maeda", "name": null }, { "creator_type": "author", "first_name": "Toshiaki", "last_name": "Kume", "name": null }, { "creator_type": "author", "first_name": "Takahiko", "last_name": "Shimizu", "name": null }, { "creator_type": "author", "first_name": "Kazuhiro", "last_name": "Irie", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/srep29038" }, "pmcid": { "normalized": "PMC4931470" }, "pmid": { "normalized": "27374357" } }, "mesh": [ { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Aged, 80 and over", "descriptor_ui": "D000369", "major_topic": false }, { "descriptor": "Alzheimer Disease", "descriptor_ui": "D000544", "major_topic": false }, { "descriptor": "Amyloid beta-Peptides", "descriptor_ui": "D016229", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Antibodies, Monoclonal", "descriptor_ui": "D000911", "major_topic": false }, { "descriptor": "Case-Control Studies", "descriptor_ui": "D016022", "major_topic": false }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Molecular Conformation", "descriptor_ui": "D008968", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Peptide Fragments", "descriptor_ui": "D010446", "major_topic": false }, { "descriptor": "Rats, Wistar", "descriptor_ui": "D017208", "major_topic": false }, { "descriptor": "Surface Plasmon Resonance", "descriptor_ui": "D020349", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016 Jul 4", "date_precision": "day", "issue": "", "normalized_date": "2016-07-04", "pages": "29038", "proceedings_title": null, "publisher": "", "title": "Scientific reports", "volume": "6", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Monoclonal antibody with conformational specificity for a toxic conformer of amyloid β42 and its application toward the Alzheimer's disease diagnosis.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The molecular carbon nanoring, cycloparaphenylene (CPP), is fascinating as a new class of carbonaceous porous solids with the uniform structure of an all-benzene surface. We explored the feasibility of [12]CPP as a carbon-based porous material and uncovered its unique adsorption properties due to its shape and highly nonpolar surface. Unlike other porous carbon solids, [12]CPP shows stepwise adsorption behaviors sensitive to the functionalities of the guest molecules. In situ powder X-ray diffraction and infrared spectra provided insights into how [12]CPP accommodates the guest molecules with structural deformation retaining its structural periodicity during the whole adsorption process, which exemplifies that this molecular nanoring represents an unprecedented carbon-based soft porous solid.", "classifications": [ { "id": "Hijikata", "label": "Group Hijikata", "parent": "Tsuchiya", "type": "group" }, { "id": "Tsuchiya", "label": "Team Tsuchiya", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Hirotoshi", "last_name": "Sakamoto", "name": null }, { "creator_type": "author", "first_name": "Toshihiko", "last_name": "Fujimori", "name": null }, { "creator_type": "author", "first_name": "Xiaolin", "last_name": "Li", "name": null }, { "creator_type": "author", "first_name": "Katsumi", "last_name": "Kaneko", "name": null }, { "creator_type": "author", "first_name": "Kai", "last_name": "Kan", "name": null }, { "creator_type": "author", "first_name": "Noriaki", "last_name": "Ozaki", "name": null }, { "creator_type": "author", "first_name": "Yuh", "last_name": "Hijikata", "name": null }, { "creator_type": "author", "first_name": "Stephan", "last_name": "Irle", "name": null }, { "creator_type": "author", "first_name": "Kenichiro", "last_name": "Itami", "name": null } ], "identifiers": { "doi": { "normalized": "10.1039/c6sc00092d" }, "pmcid": { "normalized": "PMC6013928" }, "pmid": { "normalized": "30155066" } }, "mesh": [], "publication": { "conference_name": null, "date": "2016 Jul 1", "date_precision": "day", "issue": "7", "normalized_date": "2016-07-01", "pages": "4204-4210", "proceedings_title": null, "publisher": "", "title": "Chemical science", "volume": "7", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Cycloparaphenylene as a molecular porous carbon solid with uniform pores exhibiting adsorption-induced softness.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Methylmercury (MeHg) modifies cellular proteins via their thiol groups in a process referred to as \"S-mercuration\", potentially resulting in modulation of the cellular signal transduction pathway. We examined whether low-dose MeHg could affect Akt signaling involved in cell survival. Exposure of human neuroblastoma SH-SY5Y cells of up to 2 muM MeHg phosphorylated Akt and its downstream signal molecule CREB, presumably due to inactivation of PTEN through S-mercuration. As a result, the anti-apoptotic protein Bcl-2 was up-regulated by MeHg. The activation of Akt/CREB/Bcl-2 signaling mediated by MeHg was, at least in part, linked to cellular defence because either pretreatment with wortmannin to block PI3K/Akt signaling or knockdown of Bcl-2 enhanced MeHg-mediated cytotoxicity. In contrast, increasing concentrations of MeHg disrupted Akt/CREB/Bcl-2 signaling. This phenomenon was attributed to S-mercuration of CREB through Cys286 rather than Akt. These results suggest that although MeHg is an apoptosis-inducing toxicant, this environmental electrophile is able to activate the cell survival signal transduction pathway at lower concentrations prior to apoptotic cell death.", "classifications": [ { "id": "Nishida", "label": "Group Nishida", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Takamitsu", "last_name": "Unoki", "name": null }, { "creator_type": "author", "first_name": "Yumi", "last_name": "Abiko", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Toyama", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Uehara", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Tsuboi", "name": null }, { "creator_type": "author", "first_name": "Motohiro", "last_name": "Nishida", "name": null }, { "creator_type": "author", "first_name": "Toshiyuki", "last_name": "Kaji", "name": null }, { "creator_type": "author", "first_name": "Yoshito", "last_name": "Kumagai", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/srep28944" }, "pmcid": { "normalized": "PMC4928048" }, "pmid": { "normalized": "27357941" } }, "mesh": [ { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "Cell Survival", "descriptor_ui": "D002470", "major_topic": false }, { "descriptor": "Cyclic AMP Response Element-Binding Protein", "descriptor_ui": "D017362", "major_topic": false }, { "descriptor": "Gene Expression Regulation", "descriptor_ui": "D005786", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Methylmercury Compounds", "descriptor_ui": "D008767", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Oncogene Protein v-akt", "descriptor_ui": "D051058", "major_topic": false }, { "descriptor": "Phosphorylation", "descriptor_ui": "D010766", "major_topic": false }, { "descriptor": "Protein Processing, Post-Translational", "descriptor_ui": "D011499", "major_topic": false }, { "descriptor": "Proto-Oncogene Proteins c-bcl-2", "descriptor_ui": "D019253", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Up-Regulation", "descriptor_ui": "D015854", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016 Jun 30", "date_precision": "day", "issue": "", "normalized_date": "2016-06-30", "pages": "28944", "proceedings_title": null, "publisher": "", "title": "Scientific reports", "volume": "6", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Methylmercury, an environmental electrophile capable of activation and disruption of the Akt/CREB/Bcl-2 signal transduction pathway in SH-SY5Y cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "p62/Sqstm1 is a multifunctional protein involved in cell survival, growth and death, that is degraded by autophagy. Amplification of the p62/Sqstm1 gene, and aberrant accumulation and phosphorylation of p62/Sqstm1, have been implicated in tumour development. Herein, we reveal the molecular mechanism of p62/Sqstm1-dependent malignant progression, and suggest that molecular targeting of p62/Sqstm1 represents a potential chemotherapeutic approach against hepatocellular carcinoma (HCC). Phosphorylation of p62/Sqstm1 at Ser349 directs glucose to the glucuronate pathway, and glutamine towards glutathione synthesis through activation of the transcription factor Nrf2. These changes provide HCC cells with tolerance to anti-cancer drugs and proliferation potency. Phosphorylated p62/Sqstm1 accumulates in tumour regions positive for hepatitis C virus (HCV). An inhibitor of phosphorylated p62-dependent Nrf2 activation suppresses the proliferation and anticancer agent tolerance of HCC. Our data indicate that this Nrf2 inhibitor could be used to make cancer cells less resistant to anticancer drugs, especially in HCV-positive HCC patients.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Tetsuya", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Yoshinobu", "last_name": "Ichimura", "name": null }, { "creator_type": "author", "first_name": "Keiko", "last_name": "Taguchi", "name": null }, { "creator_type": "author", "first_name": "Takafumi", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Tsunehiro", "last_name": "Mizushima", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Takagi", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Hirose", "name": null }, { "creator_type": "author", "first_name": "Masayuki", "last_name": "Nagahashi", "name": null }, { "creator_type": "author", "first_name": "Tetsuro", "last_name": "Iso", "name": null }, { "creator_type": "author", "first_name": "Toshiaki", "last_name": "Fukutomi", "name": null }, { "creator_type": "author", "first_name": "Maki", "last_name": "Ohishi", "name": null }, { "creator_type": "author", "first_name": "Keiko", "last_name": "Endo", "name": null }, { "creator_type": "author", "first_name": "Takefumi", "last_name": "Uemura", "name": null }, { "creator_type": "author", "first_name": "Yasumasa", "last_name": "Nishito", "name": null }, { "creator_type": "author", "first_name": "Shujiro", "last_name": "Okuda", "name": null }, { "creator_type": "author", "first_name": "Miki", "last_name": "Obata", "name": null }, { "creator_type": "author", "first_name": "Tsuguka", "last_name": "Kouno", "name": null }, { "creator_type": "author", "first_name": "Riyo", "last_name": "Imamura", "name": null }, { "creator_type": "author", "first_name": "Yukio", "last_name": "Tada", "name": null }, { "creator_type": "author", "first_name": "Rika", "last_name": "Obata", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Yasuda", "name": null }, { "creator_type": "author", "first_name": "Kyoko", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Tsutomu", "last_name": "Fujimura", "name": null }, { "creator_type": "author", "first_name": "Jingbo", "last_name": "Pi", "name": null }, { "creator_type": "author", "first_name": "Myung-Shik", "last_name": "Lee", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Ueno", "name": null }, { "creator_type": "author", "first_name": "Tomoyuki", "last_name": "Ohe", "name": null }, { "creator_type": "author", "first_name": "Tadahiko", "last_name": "Mashino", "name": null }, { "creator_type": "author", "first_name": "Toshifumi", "last_name": "Wakai", "name": null }, { "creator_type": "author", "first_name": "Hirotatsu", "last_name": "Kojima", "name": null }, { "creator_type": "author", "first_name": "Takayoshi", "last_name": "Okabe", "name": null }, { "creator_type": "author", "first_name": "Tetsuo", "last_name": "Nagano", "name": null }, { "creator_type": "author", "first_name": "Hozumi", "last_name": "Motohashi", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Waguri", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Masayuki", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Keiji", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Masaaki", "last_name": "Komatsu", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/ncomms12030" }, "pmcid": { "normalized": "PMC4931237" }, "pmid": { "normalized": "27345495" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Antineoplastic Agents", "descriptor_ui": "D000970", "major_topic": false }, { "descriptor": "Carcinoma, Hepatocellular", "descriptor_ui": "D006528", "major_topic": false }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Cell Survival", "descriptor_ui": "D002470", "major_topic": false }, { "descriptor": "Gene Expression Regulation, Neoplastic", "descriptor_ui": "D015972", "major_topic": false }, { "descriptor": "Hepacivirus", "descriptor_ui": "D016174", "major_topic": false }, { "descriptor": "Hepatitis C", "descriptor_ui": "D006526", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Liver Neoplasms", "descriptor_ui": "D008113", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Microarray Analysis", "descriptor_ui": "D046228", "major_topic": false }, { "descriptor": "NF-E2-Related Factor 2", "descriptor_ui": "D051267", "major_topic": false }, { "descriptor": "Sequestosome-1 Protein", "descriptor_ui": "D000071456", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016 Jun 27", "date_precision": "day", "issue": "", "normalized_date": "2016-06-27", "pages": "12030", "proceedings_title": null, "publisher": "", "title": "Nature communications", "volume": "7", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "p62/Sqstm1 promotes malignancy of HCV-positive hepatocellular carcinoma through Nrf2-dependent metabolic reprogramming.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Cellular signaling processes can exhibit pronounced cell-to-cell variability in genetically identical cells. This affects how individual cells respond differentially to the same environmental stimulus. However, the origins of cell-to-cell variability in cellular signaling systems remain poorly understood. Here, we measure the dynamics of phosphorylated MEK and ERK across cell populations and quantify the levels of population heterogeneity over time using high-throughput image cytometry. We use a statistical modeling framework to show that extrinsic noise, particularly that from upstream MEK, is the dominant factor causing cell-to-cell variability in ERK phosphorylation, rather than stochasticity in the phosphorylation/dephosphorylation of ERK. We furthermore show that without extrinsic noise in the core module, variable (including noisy) signals would be faithfully reproduced downstream, but the within-module extrinsic variability distorts these signals and leads to a drastic reduction in the mutual information between incoming signal and ERK activity.", "classifications": [ { "id": "Kuroda", "label": "Group Kuroda", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Sarah", "last_name": "Filippi", "name": null }, { "creator_type": "author", "first_name": "Chris P.", "last_name": "Barnes", "name": null }, { "creator_type": "author", "first_name": "Paul D. W.", "last_name": "Kirk", "name": null }, { "creator_type": "author", "first_name": "Takamasa", "last_name": "Kudo", "name": null }, { "creator_type": "author", "first_name": "Katsuyuki", "last_name": "Kunida", "name": null }, { "creator_type": "author", "first_name": "Siobhan S.", "last_name": "McMahon", "name": null }, { "creator_type": "author", "first_name": "Takaho", "last_name": "Tsuchiya", "name": null }, { "creator_type": "author", "first_name": "Takumi", "last_name": "Wada", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Kuroda", "name": null }, { "creator_type": "author", "first_name": "Michael P. H.", "last_name": "Stumpf", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.celrep.2016.05.024" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "27264188" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Extracellular Signal-Regulated MAP Kinases", "descriptor_ui": "D048049", "major_topic": false }, { "descriptor": "MAP Kinase Signaling System", "descriptor_ui": "D020935", "major_topic": true }, { "descriptor": "Mitogen-Activated Protein Kinase Kinases", "descriptor_ui": "D020929", "major_topic": false }, { "descriptor": "Models, Biological", "descriptor_ui": "D008954", "major_topic": false }, { "descriptor": "Models, Statistical", "descriptor_ui": "D015233", "major_topic": false }, { "descriptor": "PC12 Cells", "descriptor_ui": "D016716", "major_topic": false }, { "descriptor": "Phosphorylation", "descriptor_ui": "D010766", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Time Factors", "descriptor_ui": "D013997", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016 Jun 14", "date_precision": "day", "issue": "11", "normalized_date": "2016-06-14", "pages": "2524-2535", "proceedings_title": null, "publisher": "", "title": "Cell Reports", "volume": "15", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Robustness of MEK-ERK Dynamics and Origins of Cell-to-Cell Variability in MAPK Signaling.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Despite theoretical and physical studies implying that cell-extracellular matrix adhesion geometry governs the orientation of the cell division axis, the molecular mechanisms that translate interphase adhesion geometry to the mitotic spindle orientation remain elusive. Here, we show that the cellular edge retraction during mitotic cell rounding correlates with the spindle axis. At the onset of mitotic cell rounding, caveolin-1 is targeted to the retracting cortical region at the proximal end of retraction fibres, where ganglioside GM1-enriched membrane domains with clusters of caveola-like structures are formed in an integrin and RhoA-dependent manner. Furthermore, Galphai1-LGN-NuMA, a well-known regulatory complex of spindle orientation, is targeted to the caveolin-1-enriched cortical region to guide the spindle axis towards the cellular edge retraction. We propose that retraction-induced cortical heterogeneity of caveolin-1 during mitotic cell rounding sets the spindle orientation in the context of adhesion geometry.", "classifications": [ { "id": "Toyoshima", "label": "Group Toyoshima", "parent": "Toyoshima", "type": "group" }, { "id": "Toyoshima", "label": "Team Toyoshima", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Shigeru", "last_name": "Matsumura", "name": null }, { "creator_type": "author", "first_name": "Tomoko", "last_name": "Kojidani", "name": null }, { "creator_type": "author", "first_name": "Yuji", "last_name": "Kamioka", "name": null }, { "creator_type": "author", "first_name": "Seiichi", "last_name": "Uchida", "name": null }, { "creator_type": "author", "first_name": "Tokuko", "last_name": "Haraguchi", "name": null }, { "creator_type": "author", "first_name": "Akatsuki", "last_name": "Kimura", "name": null }, { "creator_type": "author", "first_name": "Fumiko", "last_name": "Toyoshima", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/ncomms11858" }, "pmcid": { "normalized": "PMC4910015" }, "pmid": { "normalized": "27292265" } }, "mesh": [ { "descriptor": "Caveolin 1", "descriptor_ui": "D051242", "major_topic": false }, { "descriptor": "Cell Adhesion", "descriptor_ui": "D002448", "major_topic": false }, { "descriptor": "Cholesterol", "descriptor_ui": "D002784", "major_topic": false }, { "descriptor": "Extracellular Matrix", "descriptor_ui": "D005109", "major_topic": false }, { "descriptor": "HeLa Cells", "descriptor_ui": "D006367", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Integrin beta1", "descriptor_ui": "D019012", "major_topic": false }, { "descriptor": "Interphase", "descriptor_ui": "D007399", "major_topic": true }, { "descriptor": "Membrane Microdomains", "descriptor_ui": "D021962", "major_topic": false }, { "descriptor": "Mitosis", "descriptor_ui": "D008938", "major_topic": false }, { "descriptor": "Models, Biological", "descriptor_ui": "D008954", "major_topic": false }, { "descriptor": "rhoA GTP-Binding Protein", "descriptor_ui": "D020742", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Spindle Apparatus", "descriptor_ui": "D008941", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016 Jun 13", "date_precision": "day", "issue": "", "normalized_date": "2016-06-13", "pages": "ncomms11858", "proceedings_title": null, "publisher": "", "title": "Nature communications", "volume": "7", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Interphase adhesion geometry is transmitted to an internal regulator for spindle orientation via caveolin-1.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Bright fluorescent molecules with long fluorescence lifetimes are important for the development of lifetime-based fluorescence imaging techniques. Herein, a molecular design is described for simultaneously attaining long fluorescence lifetime (tau) and high brightness (PhiF xvarepsilon) in a system that features macrocyclic dimerization of fluorescent pi-conjugated skeletons with flexible linkers. An alkylene-linked macrocyclic dimer of bis(thienylethynyl)anthracene was found to show excimer emission with a long fluorescence lifetime (tau approximately 19 ns) in solution, while maintaining high brightness. A comparison with various relevant derivatives revealed that the macrocyclic structure and the length of the alkylene chains play crucial roles in attaining these properties. In vitro time-gated imaging experiments were conducted as a proof-of-principle for the superiority of this macrocyclic fluorophore relative to the commercial fluorescent dye Alexa Fluor 488.", "classifications": [ { "id": "Sato", "label": "Group Sato", "parent": "Tsuchiya", "type": "group" }, { "id": "Tsuchiya", "label": "Team Tsuchiya", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Osaki", "name": null }, { "creator_type": "author", "first_name": "Chih-Ming", "last_name": "Chou", "name": null }, { "creator_type": "author", "first_name": "Masayasu", "last_name": "Taki", "name": null }, { "creator_type": "author", "first_name": "Kai", "last_name": "Welke", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Yokogawa", "name": null }, { "creator_type": "author", "first_name": "Stephan", "last_name": "Irle", "name": null }, { "creator_type": "author", "first_name": "Yoshikatsu", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Tetsuya", "last_name": "Higashiyama", "name": null }, { "creator_type": "author", "first_name": "Shohei", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Aiko", "last_name": "Fukazawa", "name": null }, { "creator_type": "author", "first_name": "Shigehiro", "last_name": "Yamaguchi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/anie.201602239" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "27121201" } }, "mesh": [], "publication": { "conference_name": null, "date": "2016 Jun 13", "date_precision": "day", "issue": "25", "normalized_date": "2016-06-13", "pages": "7131-7135", "proceedings_title": null, "publisher": "", "title": "Angewandte Chemie (International ed. in English)", "volume": "55", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "A Macrocyclic Fluorophore Dimer with Flexible Linkers: Bright Excimer Emission with a Long Fluorescence Lifetime.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Skeletal muscle atrophy promotes muscle weakness, limiting activities of daily living. However, mechanisms underlying atrophy remain unclear. Here, we show that skeletal muscle immobilization elevates Smad2/3 protein but not mRNA levels in muscle, promoting atrophy. Furthermore, we demonstrate that myostatin, which negatively regulates muscle hypertrophy, is dispensable for denervation-induced muscle atrophy and Smad2/3 protein accumulation. Moreover, muscle-specific Smad2/3-deficient mice exhibited significant resistance to denervation-induced muscle atrophy. In addition, expression of the atrogenes Atrogin-1 and MuRF1, which underlie muscle atrophy, did not increase in muscles of Smad2/3-deficient mice following denervation. We also demonstrate that serum starvation promotes Smad2/3 protein accumulation in C2C12 myogenic cells, an in vitro muscle atrophy model, an effect inhibited by IGF1 treatment. In vivo, we observed IGF1 receptor deactivation in immobilized muscle, even in the presence of normal levels of circulating IGF1. Denervation-induced muscle atrophy was accompanied by reduced glucose intake and elevated levels of branched-chain amino acids, effects that were Smad2/3-dependent. Thus, muscle immobilization attenuates IGF1 signals at the receptor rather than the ligand level, leading to Smad2/3 protein accumulation, muscle atrophy, and accompanying metabolic changes.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Toshimi", "last_name": "Tando", "name": null }, { "creator_type": "author", "first_name": "Akiyoshi", "last_name": "Hirayama", "name": null }, { "creator_type": "author", "first_name": "Mitsuru", "last_name": "Furukawa", "name": null }, { "creator_type": "author", "first_name": "Yuiko", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Tami", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Funayama", "name": null }, { "creator_type": "author", "first_name": "Arihiko", "last_name": "Kanaji", "name": null }, { "creator_type": "author", "first_name": "Wu", "last_name": "Hao", "name": null }, { "creator_type": "author", "first_name": "Ryuichi", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Mayu", "last_name": "Morita", "name": null }, { "creator_type": "author", "first_name": "Takatsugu", "last_name": "Oike", "name": null }, { "creator_type": "author", "first_name": "Kana", "last_name": "Miyamoto", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Masatoshi", "last_name": "Nomura", "name": null }, { "creator_type": "author", "first_name": "Akihiko", "last_name": "Yoshimura", "name": null }, { "creator_type": "author", "first_name": "Masaru", "last_name": "Tomita", "name": null }, { "creator_type": "author", "first_name": "Morio", "last_name": "Matsumoto", "name": null }, { "creator_type": "author", "first_name": "Masaya", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Yoshiaki", "last_name": "Toyama", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Miyamoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1074/jbc.m115.680579" }, "pmcid": { "normalized": "PMC4933268" }, "pmid": { "normalized": "27129272" } }, "mesh": [ { "descriptor": "Amino Acids, Branched-Chain", "descriptor_ui": "D000597", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Blotting, Western", "descriptor_ui": "D015153", "major_topic": false }, { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "Glucose", "descriptor_ui": "D005947", "major_topic": false }, { "descriptor": "Insulin-Like Growth Factor I", "descriptor_ui": "D007334", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Mice, Transgenic", "descriptor_ui": "D008822", "major_topic": false }, { "descriptor": "Muscle Denervation", "descriptor_ui": "D009121", "major_topic": false }, { "descriptor": "Muscle Fibers, Skeletal", "descriptor_ui": "D018485", "major_topic": false }, { "descriptor": "Muscle Proteins", "descriptor_ui": "D009124", "major_topic": false }, { "descriptor": "Muscle, Skeletal", "descriptor_ui": "D018482", "major_topic": false }, { "descriptor": "Muscular Atrophy", "descriptor_ui": "D009133", "major_topic": false }, { "descriptor": "Myostatin", "descriptor_ui": "D055435", "major_topic": false }, { "descriptor": "Receptor, IGF Type 1", "descriptor_ui": "D017526", "major_topic": false }, { "descriptor": "Restraint, Physical", "descriptor_ui": "D012149", "major_topic": false }, { "descriptor": "Reverse Transcriptase Polymerase Chain Reaction", "descriptor_ui": "D020133", "major_topic": false }, { "descriptor": "SKP Cullin F-Box Protein Ligases", "descriptor_ui": "D044843", "major_topic": false }, { "descriptor": "Smad2 Protein", "descriptor_ui": "D051899", "major_topic": false }, { "descriptor": "Smad3 Protein", "descriptor_ui": "D051900", "major_topic": false }, { "descriptor": "Tripartite Motif Proteins", "descriptor_ui": "D000070584", "major_topic": false }, { "descriptor": "Ubiquitin-Protein Ligases", "descriptor_ui": "D044767", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016 Jun 3", "date_precision": "day", "issue": "23", "normalized_date": "2016-06-03", "pages": "12184-12194", "proceedings_title": null, "publisher": "", "title": "The Journal of biological chemistry", "volume": "291", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Smad2/3 Proteins Are Required for Immobilization-induced Skeletal Muscle Atrophy.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Using a mathematical model of the epidermis, we propose a mechanism of epidermal homeostasis mediated by calcium dynamics. We show that calcium dynamics beneath the stratum corneum can reduce spatio-temporal fluctuations of the layered structure of the epidermis. We also demonstrate that our model can reproduce experimental results that the recovery from a barrier disruption is faster when the disrupted site is exposed to air. In particular, simulation results indicate that the recovery speed depends on the size of barrier disruption.", "classifications": [ { "id": "Nagayama", "label": "Group Nagayama", "parent": "Fujiwara", "type": "group" }, { "id": "Fujiwara", "label": "Team Fujiwara", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yasuaki", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Sawabu", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Kitahata", "name": null }, { "creator_type": "author", "first_name": "Mitsuhiro", "last_name": "Denda", "name": null }, { "creator_type": "author", "first_name": "Masaharu", "last_name": "Nagayama", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.jtbi.2016.02.032" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "26953648" } }, "mesh": [ { "descriptor": "Algorithms", "descriptor_ui": "D000465", "major_topic": true }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Calcium", "descriptor_ui": "D002118", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Cell Proliferation", "descriptor_ui": "D049109", "major_topic": false }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Epidermal Cells", "descriptor_ui": "D000078404", "major_topic": false }, { "descriptor": "Epidermis", "descriptor_ui": "D004817", "major_topic": false }, { "descriptor": "Homeostasis", "descriptor_ui": "D006706", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Keratinocytes", "descriptor_ui": "D015603", "major_topic": false }, { "descriptor": "Kinetics", "descriptor_ui": "D007700", "major_topic": false }, { "descriptor": "Models, Biological", "descriptor_ui": "D008954", "major_topic": true } ], "publication": { "conference_name": null, "date": "2016 May 21", "date_precision": "day", "issue": "", "normalized_date": "2016-05-21", "pages": "52-60", "proceedings_title": null, "publisher": "", "title": "Journal of theoretical biology", "volume": "397", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Mathematical model for calcium-assisted epidermal homeostasis.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "A scandium-triflate-catalyzed arylative desulfonation of diarylmethyl phenyl sulfones with arenes and heteroarenes was established. A variety of both sulfone and arene substrates were reacted to afford symmetric and nonsymmetric triarylmethanes in good yields. Further transformations of the resulting triarylmethanes and application to the concise synthesis of a bactericidal agent analogue were also demonstrated.", "classifications": [ { "id": "Nanbo", "label": "Group Nanbo", "parent": "Tsuchiya", "type": "group" }, { "id": "Tsuchiya", "label": "Team Tsuchiya", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Masakazu", "last_name": "Nambo", "name": null }, { "creator_type": "author", "first_name": "Zachary T.", "last_name": "Ariki", "name": null }, { "creator_type": "author", "first_name": "Daniel", "last_name": "Canseco-Gonzalez", "name": null }, { "creator_type": "author", "first_name": "D. Dawson", "last_name": "Beattie", "name": null }, { "creator_type": "author", "first_name": "Cathleen M.", "last_name": "Crudden", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/acs.orglett.6b00744" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "27124389" } }, "mesh": [], "publication": { "conference_name": null, "date": "2016 May 20", "date_precision": "day", "issue": "10", "normalized_date": "2016-05-20", "pages": "2339-2342", "proceedings_title": null, "publisher": "", "title": "Organic letters", "volume": "18", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Arylative Desulfonation of Diarylmethyl Phenyl Sulfone with Arenes Catalyzed by Scandium Triflate.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "A critical issue in the management of chronic kidney disease (CKD) is to prevent patients from the progression to end-stage kidney disease (ESKD), however, there is only limited number of biomarkers for the discrimination of the high-risk CKD patients. We aimed to identify the metabolites which possess the ability to predict the earlier kidney deterioration. We performed capillary electrophoresis and liquid chromatography mass spectrometry (CE-MS)-based metabolic profiling in a prospective cohort, which consisted of referred 112 CKD patients with median follow-up period of 4.4 years. The association between the levels of candidate metabolites and the outcomes (progression to ESKD alone or in combination with death before ESKD) were assessed by multivariate Cox proportional hazard models after adjusting for the baseline covariates. A total of 218 metabolites were detected in the plasma of CKD patients. We identified 16 metabolites which have predictive values for the composite outcome: The risk for composite outcome was elevated from 2.0- to 8.0-fold in those with higher levels of 16 plasma metabolites. Our results suggest that the measurement of these metabolites may facilitate CKD management by predicting the risk of progression to ESKD.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Tomonori", "last_name": "Kimura", "name": null }, { "creator_type": "author", "first_name": "Keiko", "last_name": "Yasuda", "name": null }, { "creator_type": "author", "first_name": "Ryohei", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Hiromi", "last_name": "Rakugi", "name": null }, { "creator_type": "author", "first_name": "Terumasa", "last_name": "Hayashi", "name": null }, { "creator_type": "author", "first_name": "Yoshitaka", "last_name": "Isaka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/srep26138" }, "pmcid": { "normalized": "PMC4870629" }, "pmid": { "normalized": "27188985" } }, "mesh": [ { "descriptor": "Amino Acids", "descriptor_ui": "D000596", "major_topic": false }, { "descriptor": "Biomarkers", "descriptor_ui": "D015415", "major_topic": false }, { "descriptor": "Chromatography, Liquid", "descriptor_ui": "D002853", "major_topic": false }, { "descriptor": "Electrophoresis, Capillary", "descriptor_ui": "D019075", "major_topic": false }, { "descriptor": "Follow-Up Studies", "descriptor_ui": "D005500", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Isomerism", "descriptor_ui": "D007536", "major_topic": false }, { "descriptor": "Kidney Failure, Chronic", "descriptor_ui": "D007676", "major_topic": false }, { "descriptor": "Mass Spectrometry", "descriptor_ui": "D013058", "major_topic": false }, { "descriptor": "Metabolomics", "descriptor_ui": "D055432", "major_topic": false }, { "descriptor": "Plasma", "descriptor_ui": "D010949", "major_topic": false }, { "descriptor": "Prognosis", "descriptor_ui": "D011379", "major_topic": false }, { "descriptor": "Prospective Studies", "descriptor_ui": "D011446", "major_topic": false }, { "descriptor": "Renal Insufficiency, Chronic", "descriptor_ui": "D051436", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016 May 18", "date_precision": "day", "issue": "", "normalized_date": "2016-05-18", "pages": "26138", "proceedings_title": null, "publisher": "", "title": "Scientific reports", "volume": "6", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Identification of biomarkers for development of end-stage kidney disease in chronic kidney disease by metabolomic profiling.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "5-aminolevulinic acid (5-ALA)-based fluorescence diagnosis is now clinically applied for accurate and ultrarapid diagnosis of malignant lesions such as lymph node metastasis during surgery. 5-ALA-based diagnosis evaluates fluorescence intensity of a fluorescent metabolite of 5-ALA, protoporphyrin IX (PPIX); however, the fluorescence of PPIX is often affected by autofluorescence of tissue chromophores, such as collagen and flavins. In this study, we demonstrated PPIX fluorescence estimation with autofluorescence elimination for 5-ALA-based fluorescence diagnosis of malignant lesions by simplified and optimized multispectral imaging. We computationally optimized observation wavelength regions for the estimation of PPIX fluorescence in terms of minimizing prediction error of PPIX fluorescence intensity in the presence of typical chromophores, collagen and flavins. By using the fluorescence intensities of the optimized wavelength regions, we verified quantitative detection of PPIX fluorescence by using chemical mixtures of PPIX, flavins, and collagen. Furthermore, we demonstrated detection capability by using metastatic and non-metastatic lymph nodes of colorectal cancer patients. These results suggest the potential and usefulness of the background-free estimation method of PPIX fluorescence for 5-ALA-based fluorescence diagnosis of malignant lesions, and we expect this method to be beneficial for intraoperative and rapid cancer diagnosis.", "classifications": [ { "id": "Tanaka", "label": "Group Tanaka", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Takeo", "last_name": "Minamikawa", "name": null }, { "creator_type": "author", "first_name": "Hisataka", "last_name": "Matsuo", "name": null }, { "creator_type": "author", "first_name": "Yoshiyuki", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Yoshinori", "last_name": "Harada", "name": null }, { "creator_type": "author", "first_name": "Eigo", "last_name": "Otsuji", "name": null }, { "creator_type": "author", "first_name": "Akio", "last_name": "Yanagisawa", "name": null }, { "creator_type": "author", "first_name": "Hideo", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Tetsuro", "last_name": "Takamatsu", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/srep25530" }, "pmcid": { "normalized": "PMC4857744" }, "pmid": { "normalized": "27149301" } }, "mesh": [ { "descriptor": "Aminolevulinic Acid", "descriptor_ui": "D000622", "major_topic": false }, { "descriptor": "Biotransformation", "descriptor_ui": "D001711", "major_topic": false }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Collagen", "descriptor_ui": "D003094", "major_topic": false }, { "descriptor": "Colorectal Neoplasms", "descriptor_ui": "D015179", "major_topic": false }, { "descriptor": "Flavins", "descriptor_ui": "D005415", "major_topic": false }, { "descriptor": "Fluorescent Dyes", "descriptor_ui": "D005456", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Image Processing, Computer-Assisted", "descriptor_ui": "D007091", "major_topic": false }, { "descriptor": "Lymph Node Excision", "descriptor_ui": "D008197", "major_topic": false }, { "descriptor": "Lymph Nodes", "descriptor_ui": "D008198", "major_topic": false }, { "descriptor": "Lymphatic Metastasis", "descriptor_ui": "D008207", "major_topic": false }, { "descriptor": "Optical Imaging", "descriptor_ui": "D061848", "major_topic": false }, { "descriptor": "Protoporphyrins", "descriptor_ui": "D011524", "major_topic": false }, { "descriptor": "Signal-To-Noise Ratio", "descriptor_ui": "D059629", "major_topic": false }, { "descriptor": "Software", "descriptor_ui": "D012984", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016 May 5", "date_precision": "day", "issue": "", "normalized_date": "2016-05-05", "pages": "25530", "proceedings_title": null, "publisher": "", "title": "Scientific reports", "volume": "6", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Simplified and optimized multispectral imaging for 5-ALA-based fluorescence diagnosis of malignant lesions.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The progression from precursor lesions of pancreatic cancer, including pancreatic intraepithelial neoplasia and intraductal papillary mucinous neoplasm (IPMN), to invasive disease is characterized by stepwise accumulation of genetic alterations. However, it remains unclear whether additional alterations are required for the progression of high-grade neoplasms to invasive pancreatic carcinoma. We compared the genomic profiles of paired noninvasive and invasive carcinoma tissues collected from patients with IPMN. We demonstrate that the frequency of genomic copy-number aberrations significantly increased during the course of invasion, and the loss of 8p11.22-ter was more often associated with invasive tissues. Expression profiling in pancreatic cancer cell lines with and without 8p11.22-ter revealed that DUSP4, an MAPK phosphatase, was significantly downregulated in cells lacking 8p11.22-ter as well as in invasive carcinomas due to genomic loss. Restoration of DUSP4 expression in pancreatic cancer cells significantly suppressed invasiveness and anoikis resistance via ERK inactivation. Accordingly, we found that blockade of ERK signaling by MEK inhibition was effective in an orthotopic xenograft model and significantly extended survival. Collectively, our findings demonstrate a genetic mechanism by which pancreatic precursor lesions progress to invasive carcinomas and highlight DUSP4 as a novel invasion suppressor that can be therapeutically exploited through manipulation of ERK signaling. Cancer Res; 76(9); 2612-25. (c)2016 AACR.", "classifications": [ { "id": "Takekawa", "label": "Group Takekawa", "parent": "Takekawa", "type": "group" }, { "id": "Takekawa", "label": "Team Takekawa", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Naoki", "last_name": "Hijiya", "name": null }, { "creator_type": "author", "first_name": "Yoshiyuki", "last_name": "Tsukamoto", "name": null }, { "creator_type": "author", "first_name": "Chisato", "last_name": "Nakada", "name": null }, { "creator_type": "author", "first_name": "Lam", "last_name": "Tung Nguyen", "name": null }, { "creator_type": "author", "first_name": "Tomoki", "last_name": "Kai", "name": null }, { "creator_type": "author", "first_name": "Keiko", "last_name": "Matsuura", "name": null }, { "creator_type": "author", "first_name": "Kohei", "last_name": "Shibata", "name": null }, { "creator_type": "author", "first_name": "Masafumi", "last_name": "Inomata", "name": null }, { "creator_type": "author", "first_name": "Tomohisa", "last_name": "Uchida", "name": null }, { "creator_type": "author", "first_name": "Akinori", "last_name": "Tokunaga", "name": null }, { "creator_type": "author", "first_name": "Kohei", "last_name": "Amada", "name": null }, { "creator_type": "author", "first_name": "Kuniaki", "last_name": "Shirao", "name": null }, { "creator_type": "author", "first_name": "Yasunari", "last_name": "Yamada", "name": null }, { "creator_type": "author", "first_name": "Hiromu", "last_name": "Mori", "name": null }, { "creator_type": "author", "first_name": "Ichiro", "last_name": "Takeuchi", "name": null }, { "creator_type": "author", "first_name": "Masao", "last_name": "Seto", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Aoki", "name": null }, { "creator_type": "author", "first_name": "Mutsuhiro", "last_name": "Takekawa", "name": null }, { "creator_type": "author", "first_name": "Masatsugu", "last_name": "Moriyama", "name": null } ], "identifiers": { "doi": { "normalized": "10.1158/0008-5472.can-15-1846" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "26941286" } }, "mesh": [ { "descriptor": "Adenocarcinoma in Situ", "descriptor_ui": "D065311", "major_topic": false }, { "descriptor": "Adenocarcinoma, Mucinous", "descriptor_ui": "D002288", "major_topic": false }, { "descriptor": "Adenocarcinoma, Papillary", "descriptor_ui": "D000231", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Carcinoma, Pancreatic Ductal", "descriptor_ui": "D021441", "major_topic": false }, { "descriptor": "Comparative Genomic Hybridization", "descriptor_ui": "D055028", "major_topic": false }, { "descriptor": "Disease Progression", "descriptor_ui": "D018450", "major_topic": false }, { "descriptor": "Dual-Specificity Phosphatases", "descriptor_ui": "D054637", "major_topic": false }, { "descriptor": "Heterografts", "descriptor_ui": "D064593", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Kaplan-Meier Estimate", "descriptor_ui": "D053208", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Microscopy, Confocal", "descriptor_ui": "D018613", "major_topic": false }, { "descriptor": "Mitogen-Activated Protein Kinase Phosphatases", "descriptor_ui": "D054639", "major_topic": false }, { "descriptor": "Neoplasm Invasiveness", "descriptor_ui": "D009361", "major_topic": false }, { "descriptor": "Oligonucleotide Array Sequence Analysis", "descriptor_ui": "D020411", "major_topic": false }, { "descriptor": "Pancreatic Neoplasms", "descriptor_ui": "D010190", "major_topic": false }, { "descriptor": "Transcriptome", "descriptor_ui": "D059467", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016 May 1", "date_precision": "day", "issue": "9", "normalized_date": "2016-05-01", "pages": "2612-2625", "proceedings_title": null, "publisher": "", "title": "Cancer research", "volume": "76", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Genomic Loss of DUSP4 Contributes to the Progression of Intraepithelial Neoplasm of Pancreas to Invasive Carcinoma.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Precise directional control of pollen-tube growth by pistil tissue is critical for successful fertilization of flowering plants [1-3]. Ovular attractant peptides, which are secreted from two synergid cells on the side of the egg cell, have been identified [4-6]. Emerging evidence suggests that the ovular directional cue is not sufficient for successful guidance but that competency control by the pistil is critical for the response of pollen tubes to the attraction signal [1, 3, 7]. However, the female molecule for this competency induction has not been reported. Here we report that ovular methyl-glucuronosyl arabinogalactan (AMOR) induces competency of the pollen tube to respond to ovular attractant LURE peptides in Torenia fournieri. We developed a method for assaying the response capability of a pollen tube by micromanipulating an ovule. Using this method, we showed that pollen tubes growing through a cut style acquired a response capability in the medium by receiving a sufficient amount of a factor derived from mature ovules of Torenia. This factor, named AMOR, was identified as an arabinogalactan polysaccharide, the terminal 4-O-methyl-glucuronosyl residue of which was necessary for its activity. Moreover, a chemically synthesized disaccharide, the beta isomer of methyl-glucuronosyl galactose (4-Me-GlcA-beta-(1-->6)-Gal), showed AMOR activity. No specific sugar-chain structure of plant extracellular matrix has been identified as a bioactive molecule involved in intercellular communication. We suggest that the AMOR sugar chain in the ovary renders the pollen tube competent to the chemotropic response prior to final guidance by LURE peptides.", "classifications": [ { "id": "Sato", "label": "Group Sato", "parent": "Tsuchiya", "type": "group" }, { "id": "Tsuchiya", "label": "Team Tsuchiya", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Akane G.", "last_name": "Mizukami", "name": null }, { "creator_type": "author", "first_name": "Rie", "last_name": "Inatsugi", "name": null }, { "creator_type": "author", "first_name": "Jiao", "last_name": "Jiao", "name": null }, { "creator_type": "author", "first_name": "Toshihisa", "last_name": "Kotake", "name": null }, { "creator_type": "author", "first_name": "Keiko", "last_name": "Kuwata", "name": null }, { "creator_type": "author", "first_name": "Kento", "last_name": "Ootani", "name": null }, { "creator_type": "author", "first_name": "Satohiro", "last_name": "Okuda", "name": null }, { "creator_type": "author", "first_name": "Subramanian", "last_name": "Sankaranarayanan", "name": null }, { "creator_type": "author", "first_name": "Yoshikatsu", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Maruyama", "name": null }, { "creator_type": "author", "first_name": "Hiroaki", "last_name": "Iwai", "name": null }, { "creator_type": "author", "first_name": "Estelle", "last_name": "Garenaux", "name": null }, { "creator_type": "author", "first_name": "Chihiro", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Ken", "last_name": "Kitajima", "name": null }, { "creator_type": "author", "first_name": "Yoichi", "last_name": "Tsumuraya", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Mori", "name": null }, { "creator_type": "author", "first_name": "Junichiro", "last_name": "Yamaguchi", "name": null }, { "creator_type": "author", "first_name": "Kenichiro", "last_name": "Itami", "name": null }, { "creator_type": "author", "first_name": "Narie", "last_name": "Sasaki", "name": null }, { "creator_type": "author", "first_name": "Tetsuya", "last_name": "Higashiyama", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.cub.2016.02.040" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "27068416" } }, "mesh": [ { "descriptor": "Galactans", "descriptor_ui": "D005685", "major_topic": false }, { "descriptor": "Mucoproteins", "descriptor_ui": "D009088", "major_topic": false }, { "descriptor": "Ovule", "descriptor_ui": "D056771", "major_topic": false }, { "descriptor": "Plant Proteins", "descriptor_ui": "D010940", "major_topic": false }, { "descriptor": "Pollen Tube", "descriptor_ui": "D053205", "major_topic": false }, { "descriptor": "Reproduction", "descriptor_ui": "D012098", "major_topic": false }, { "descriptor": "Tracheophyta", "descriptor_ui": "D064028", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016 Apr 25", "date_precision": "day", "issue": "8", "normalized_date": "2016-04-25", "pages": "1091-1097", "proceedings_title": null, "publisher": "", "title": "Current biology : CB", "volume": "26", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "The AMOR Arabinogalactan Sugar Chain Induces Pollen-Tube Competency to Respond to Ovular Guidance.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The contractile forces in individual cells drive the tissue processes, such as morphogenesis and wound healing, and maintain tissue integrity. In these processes, alpha-catenin molecule acts as a tension sensor at cadherin-based adherens junctions (AJs), accelerating the positive feedback of intercellular tension. Under tension, alpha-catenin is activated to recruit vinculin, which recruits actin filaments to AJs. In this study, we revealed how alpha-catenin retains its activated state while avoiding unfolding under tension. Using single-molecule force spectroscopy employing atomic force microscopy (AFM), we found that mechanically activated alpha-catenin fragment had higher mechanical stability than a non-activated fragment. The results of our experiments using mutated and segmented fragments showed that the key intramolecular interactions acted as a conformational switch. We also found that the conformation of alpha-catenin was reinforced by vinculin binding. We demonstrate that alpha-catenin adaptively changes its conformation under tension to a stable intermediate state, binds to vinculin, and finally settles into a more stable state reinforced by vinculin binding. Our data suggest that the plastic characteristics of alpha-catenin, revealed in response to both mechanical and biochemical cues, enable the functional-structural dynamics at the cellular and tissue levels.", "classifications": [ { "id": "Maki", "label": "Group Maki", "parent": "Toyoshima", "type": "group" }, { "id": "Toyoshima", "label": "Team Toyoshima", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Koichiro", "last_name": "Maki", "name": null }, { "creator_type": "author", "first_name": "Sung-Woong", "last_name": "Han", "name": null }, { "creator_type": "author", "first_name": "Yoshinori", "last_name": "Hirano", "name": null }, { "creator_type": "author", "first_name": "Shigenobu", "last_name": "Yonemura", "name": null }, { "creator_type": "author", "first_name": "Toshio", "last_name": "Hakoshima", "name": null }, { "creator_type": "author", "first_name": "Taiji", "last_name": "Adachi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/srep24878" }, "pmcid": { "normalized": "PMC4843013" }, "pmid": { "normalized": "27109499" } }, "mesh": [ { "descriptor": "Adherens Junctions", "descriptor_ui": "D022005", "major_topic": false }, { "descriptor": "alpha Catenin", "descriptor_ui": "D051178", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Mechanical Phenomena", "descriptor_ui": "D055595", "major_topic": true }, { "descriptor": "Mechanotransduction, Cellular", "descriptor_ui": "D040542", "major_topic": true }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Microscopy, Atomic Force", "descriptor_ui": "D018625", "major_topic": false }, { "descriptor": "Protein Conformation", "descriptor_ui": "D011487", "major_topic": false }, { "descriptor": "Protein Folding", "descriptor_ui": "D017510", "major_topic": false }, { "descriptor": "Single Molecule Imaging", "descriptor_ui": "D000072760", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016 Apr 25", "date_precision": "day", "issue": "", "normalized_date": "2016-04-25", "pages": "24878", "proceedings_title": null, "publisher": "", "title": "Scientific reports", "volume": "6", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Mechano-adaptive sensory mechanism of alpha-catenin under tension.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Sperm induce Ca(2+) waves in the fertilized egg by introducing soluble factors or by surface interactions, which activate egg Ca(2+) channels. Involvement of sperm Ca(2+) channels is predicted by the conduit model; however, this model has not been validated. In Caenorhabditis elegans, the sperm-specific TRP family Ca(2+) channel TRP-3 mediates sperm-oocyte fusion. Here, using high-speed in vivo imaging and image analyses, we show that sperm induce an immediate local Ca(2+) rise followed by a Ca(2+) wave in fertilized C. elegans oocytes. Oocytes fertilized by rare trp-3 escaper sperm showed a lack of local rise and a delay in onset of the Ca(2+) wave. Sperm Ca(2+) imaging suggests that the local rise is not due to the bolus introduction of stored Ca(2+). These results suggest that, along with its primary function in sperm-oocyte fusion, TRP-3 induces Ca(2+) waves in fertilized oocytes, consistent with the conduit model.", "classifications": [ { "id": "Onami", "label": "Group Onami", "parent": "Fujiwara", "type": "group" }, { "id": "Fujiwara", "label": "Team Fujiwara", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Jun", "last_name": "Takayama", "name": null }, { "creator_type": "author", "first_name": "Shuichi", "last_name": "Onami", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.celrep.2016.03.040" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "27068469" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Animals, Genetically Modified", "descriptor_ui": "D030801", "major_topic": false }, { "descriptor": "Caenorhabditis elegans", "descriptor_ui": "D017173", "major_topic": false }, { "descriptor": "Caenorhabditis elegans Proteins", "descriptor_ui": "D029742", "major_topic": false }, { "descriptor": "Calcium Channels", "descriptor_ui": "D015220", "major_topic": false }, { "descriptor": "Calcium Signaling", "descriptor_ui": "D020013", "major_topic": true }, { "descriptor": "Fertilization", "descriptor_ui": "D005306", "major_topic": true }, { "descriptor": "Gene Expression Regulation, Developmental", "descriptor_ui": "D018507", "major_topic": false }, { "descriptor": "Genetic Loci", "descriptor_ui": "D056426", "major_topic": false }, { "descriptor": "Homeostasis", "descriptor_ui": "D006706", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Membrane Fusion", "descriptor_ui": "D008561", "major_topic": false }, { "descriptor": "Models, Biological", "descriptor_ui": "D008954", "major_topic": false }, { "descriptor": "Oocytes", "descriptor_ui": "D009865", "major_topic": false }, { "descriptor": "Spermatozoa", "descriptor_ui": "D013094", "major_topic": false }, { "descriptor": "Time Factors", "descriptor_ui": "D013997", "major_topic": false }, { "descriptor": "Transgenes", "descriptor_ui": "D019076", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016 Apr 19", "date_precision": "day", "issue": "3", "normalized_date": "2016-04-19", "pages": "625-637", "proceedings_title": null, "publisher": "", "title": "Cell reports", "volume": "15", "year": 2016 }, "ssbd": { "database": [ "ssbd-database-000012" ], "repository": [ "ssbd-repos-000012" ] }, "title": "The Sperm TRP-3 Channel Mediates the Onset of a Ca(2+) Wave in the Fertilized C. elegans Oocyte.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "We previously reported that the histone lysine methyltransferase SUV39H2, which is overexpressed in various types of human cancer, plays a critical role in the DNA repair after double strand breakage, and possesses oncogenic activity. Although its biological significance in tumorigenesis has been elucidated, the regulatory mechanism of SUV39H2 activity through post-translational modification is not well known. In this study, we demonstrate in vitro and in vivo automethylation of SUV39H2 at lysine 392. Automethylation of SUV39H2 led to impairment of its binding affinity to substrate proteins such as histone H3 and LSD1. Furthermore, we observed that hyper-automethylated SUV39H2 reduced methylation activities to substrates through affecting the binding affinity to substrate proteins. Our finding unveils a novel autoregulatory mechanism of SUV39H2 through lysine automethylation.", "classifications": [ { "id": "Hamamoto", "label": "Group Hamamoto", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Lianhua", "last_name": "Piao", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Nakakido", "name": null }, { "creator_type": "author", "first_name": "Takehiro", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Naoshi", "last_name": "Dohmae", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Ryuji", "last_name": "Hamamoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.18632/oncotarget.8072" }, "pmcid": { "normalized": "PMC5008405" }, "pmid": { "normalized": "26988914" } }, "mesh": [ { "descriptor": "DNA Methylation", "descriptor_ui": "D019175", "major_topic": false }, { "descriptor": "HEK293 Cells", "descriptor_ui": "D057809", "major_topic": false }, { "descriptor": "Histone-Lysine N-Methyltransferase", "descriptor_ui": "D011495", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Lysine", "descriptor_ui": "D008239", "major_topic": false }, { "descriptor": "Protein Binding", "descriptor_ui": "D011485", "major_topic": false }, { "descriptor": "Protein Processing, Post-Translational", "descriptor_ui": "D011499", "major_topic": false }, { "descriptor": "Substrate Specificity", "descriptor_ui": "D013379", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016 Apr 19", "date_precision": "day", "issue": "16", "normalized_date": "2016-04-19", "pages": "22846-22856", "proceedings_title": null, "publisher": "", "title": "Oncotarget", "volume": "7", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Automethylation of SUV39H2, an oncogenic histone lysine methyltransferase, regulates its binding affinity to substrate proteins.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "EWS-FLI1, a multi-functional fusion oncogene, is exclusively detected in Ewing sarcomas. However, previous studies reported that rare varieties of osteosarcomas also harbor EWS-ETS family fusion. Here, using the doxycycline-inducible EWS-FLI1 system, we established an EWS-FLI1-dependent osteosarcoma model from murine bone marrow stromal cells. We revealed that the withdrawal of EWS-FLI1 expression enhances the osteogenic differentiation of sarcoma cells, leading to mature bone formation. Taking advantage of induced pluripotent stem cell (iPSC) technology, we also show that sarcoma-derived iPSCs with cancer-related genetic abnormalities exhibited an impaired differentiation program of osteogenic lineage irrespective of the EWS-FLI1 expression. Finally, we demonstrate that EWS-FLI1 contributed to secondary sarcoma development from the sarcoma iPSCs after osteogenic differentiation. These findings demonstrate that modulating cellular differentiation is a fundamental principle of EWS-FLI1-induced osteosarcoma development. This in vitro cancer model using sarcoma iPSCs should provide a unique platform for dissecting relationships between the cancer genome and cellular differentiation.", "classifications": [ { "id": "Yamamoto", "label": "Group Yamamoto", "parent": "Toyoshima", "type": "group" }, { "id": "Toyoshima", "label": "Team Toyoshima", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Shingo", "last_name": "Komura", "name": null }, { "creator_type": "author", "first_name": "Katsunori", "last_name": "Semi", "name": null }, { "creator_type": "author", "first_name": "Fumiaki", "last_name": "Itakura", "name": null }, { "creator_type": "author", "first_name": "Hirofumi", "last_name": "Shibata", "name": null }, { "creator_type": "author", "first_name": "Takatoshi", "last_name": "Ohno", "name": null }, { "creator_type": "author", "first_name": "Akitsu", "last_name": "Hotta", "name": null }, { "creator_type": "author", "first_name": "Knut", "last_name": "Woltjen", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Haruhiko", "last_name": "Akiyama", "name": null }, { "creator_type": "author", "first_name": "Yasuhiro", "last_name": "Yamada", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.stemcr.2016.02.009" }, "pmcid": { "normalized": "PMC4834047" }, "pmid": { "normalized": "26997645" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Blotting, Western", "descriptor_ui": "D015153", "major_topic": false }, { "descriptor": "Bone Neoplasms", "descriptor_ui": "D001859", "major_topic": false }, { "descriptor": "Carcinogenesis", "descriptor_ui": "D063646", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Cell Lineage", "descriptor_ui": "D019070", "major_topic": false }, { "descriptor": "Cell Transformation, Neoplastic", "descriptor_ui": "D002471", "major_topic": false }, { "descriptor": "Gene Expression Profiling", "descriptor_ui": "D020869", "major_topic": false }, { "descriptor": "Gene Expression Regulation, Neoplastic", "descriptor_ui": "D015972", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Induced Pluripotent Stem Cells", "descriptor_ui": "D057026", "major_topic": false }, { "descriptor": "Mice, Inbred BALB C", "descriptor_ui": "D008807", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Nude", "descriptor_ui": "D008819", "major_topic": false }, { "descriptor": "Mice, SCID", "descriptor_ui": "D016513", "major_topic": false }, { "descriptor": "Oncogene Proteins, Fusion", "descriptor_ui": "D015514", "major_topic": false }, { "descriptor": "Osteogenesis", "descriptor_ui": "D010012", "major_topic": false }, { "descriptor": "Osteosarcoma", "descriptor_ui": "D012516", "major_topic": false }, { "descriptor": "Proto-Oncogene Protein c-fli-1", "descriptor_ui": "D051789", "major_topic": false }, { "descriptor": "Reverse Transcriptase Polymerase Chain Reaction", "descriptor_ui": "D020133", "major_topic": false }, { "descriptor": "RNA-Binding Protein EWS", "descriptor_ui": "D034802", "major_topic": false }, { "descriptor": "Transplantation, Heterologous", "descriptor_ui": "D014183", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016 Apr 12", "date_precision": "day", "issue": "4", "normalized_date": "2016-04-12", "pages": "592-606", "proceedings_title": null, "publisher": "", "title": "Stem cell reports", "volume": "6", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "An EWS-FLI1-Induced Osteosarcoma Model Unveiled a Crucial Role of Impaired Osteogenic Differentiation on Osteosarcoma Development.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "While implicated in therapeutic resistance, malignant progenitor cell cycle kinetics have been difficult to quantify in real-time. We developed an efficient lentiviral bicistronic fluorescent, ubiquitination-based cell cycle indicator reporter (Fucci2BL) to image live single progenitors on a defined niche coupled with cell cycle gene expression analysis. We have identified key differences in cell cycle regulatory gene expression and transit times between normal and chronic myeloid leukemia progenitors that may inform cancer stem cell eradication strategies.", "classifications": [ { "id": "Sawano", "label": "Group Sawano", "parent": "Shintaku", "type": "group" }, { "id": "Shintaku", "label": "Team Shintaku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Gabriel", "last_name": "Pineda", "name": null }, { "creator_type": "author", "first_name": "Kathleen M.", "last_name": "Lennon", "name": null }, { "creator_type": "author", "first_name": "Nathaniel P.", "last_name": "Delos Santos", "name": null }, { "creator_type": "author", "first_name": "Florence", "last_name": "Lambert-Fliszar", "name": null }, { "creator_type": "author", "first_name": "Gennarina L.", "last_name": "Riso", "name": null }, { "creator_type": "author", "first_name": "Elisa", "last_name": "Lazzari", "name": null }, { "creator_type": "author", "first_name": "Marco A.", "last_name": "Marra", "name": null }, { "creator_type": "author", "first_name": "Sheldon", "last_name": "Morris", "name": null }, { "creator_type": "author", "first_name": "Asako", "last_name": "Sakaue-Sawano", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Miyawaki", "name": null }, { "creator_type": "author", "first_name": "Catriona H. M.", "last_name": "Jamieson", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/srep23885" }, "pmcid": { "normalized": "PMC4819192" }, "pmid": { "normalized": "27041210" } }, "mesh": [ { "descriptor": "Cell Cycle", "descriptor_ui": "D002453", "major_topic": false }, { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "Coculture Techniques", "descriptor_ui": "D018920", "major_topic": false }, { "descriptor": "Drug Resistance, Neoplasm", "descriptor_ui": "D019008", "major_topic": false }, { "descriptor": "Gene Expression Profiling", "descriptor_ui": "D020869", "major_topic": false }, { "descriptor": "Gene Expression Regulation, Neoplastic", "descriptor_ui": "D015972", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Kinetics", "descriptor_ui": "D007700", "major_topic": false }, { "descriptor": "Leukemia, Myelogenous, Chronic, BCR-ABL Positive", "descriptor_ui": "D015464", "major_topic": false }, { "descriptor": "Microscopy, Confocal", "descriptor_ui": "D018613", "major_topic": false }, { "descriptor": "Neoplastic Stem Cells", "descriptor_ui": "D014411", "major_topic": false }, { "descriptor": "Sequence Analysis, RNA", "descriptor_ui": "D017423", "major_topic": false }, { "descriptor": "Stem Cell Niche", "descriptor_ui": "D055153", "major_topic": true }, { "descriptor": "Time-Lapse Imaging", "descriptor_ui": "D059008", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016 Apr 4", "date_precision": "day", "issue": "", "normalized_date": "2016-04-04", "pages": "23885", "proceedings_title": null, "publisher": "", "title": "Scientific reports", "volume": "6", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Tracking of Normal and Malignant Progenitor Cell Cycle Transit in a Defined Niche.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The Suzuki-Miyaura cross-coupling is one of the most often utilized reactions in the synthesis of pharmaceutical compounds and conjugated materials. In its most common form, the reaction joins two sp(2)-functionalized carbon atoms to make a biaryl or diene/polyene unit. These substructures are widely found in natural products and small molecules and thus the Suzuki-Miyaura cross-coupling has been proposed as the key reaction for the automated assembly of such molecules, using protecting group chemistry to affect iterative coupling. We present herein, a significant advance in this approach, in which multiply functionalized cross-coupling partners can be employed in iterative coupling without the use of protecting groups. To accomplish this, the orthogonal reactivity of different boron substituents towards the boron-to-palladium transmetalation reaction is exploited. The approach is illustrated in the preparation of chiral enantioenriched compounds, which are known to be privileged structures in active pharmaceutical compounds.", "classifications": [ { "id": "Nanbo", "label": "Group Nanbo", "parent": "Tsuchiya", "type": "group" }, { "id": "Tsuchiya", "label": "Team Tsuchiya", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Cathleen M.", "last_name": "Crudden", "name": null }, { "creator_type": "author", "first_name": "Christopher", "last_name": "Ziebenhaus", "name": null }, { "creator_type": "author", "first_name": "Jason P. G.", "last_name": "Rygus", "name": null }, { "creator_type": "author", "first_name": "Kazem", "last_name": "Ghozati", "name": null }, { "creator_type": "author", "first_name": "Phillip J.", "last_name": "Unsworth", "name": null }, { "creator_type": "author", "first_name": "Masakazu", "last_name": "Nambo", "name": null }, { "creator_type": "author", "first_name": "Samantha", "last_name": "Voth", "name": null }, { "creator_type": "author", "first_name": "Marieke", "last_name": "Hutchinson", "name": null }, { "creator_type": "author", "first_name": "Veronique S.", "last_name": "Laberge", "name": null }, { "creator_type": "author", "first_name": "Yuuki", "last_name": "Maekawa", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Imao", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/ncomms11065" }, "pmcid": { "normalized": "PMC4822017" }, "pmid": { "normalized": "27040494" } }, "mesh": [], "publication": { "conference_name": null, "date": "2016 Apr 4", "date_precision": "day", "issue": "", "normalized_date": "2016-04-04", "pages": "11065", "proceedings_title": null, "publisher": "", "title": "Nature communications", "volume": "7", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Iterative protecting group-free cross-coupling leading to chiral multiply arylated structures.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Reactive oxygen (oxidant) and free radical species are known to cause nonspecific damage of various biological molecules. The oxidant toxicology is developing an emerging concept of the physiological functions of reactive oxygen species in cell signaling regulation. Redox signaling is precisely modulated by endogenous electrophilic substances that are generated from reactive oxygen species during cellular oxidative stress responses. Among diverse electrophilic molecular species that are endogenously generated, 8-nitroguanosine 3',5'-cyclic monophosphate (8-nitro-cGMP) is a unique second messenger whose formation, signaling, and metabolism in cells was recently clarified. Most important, our current studies revealed that reactive cysteine persulfides that are formed abundantly in cells are critically involved in the metabolism of 8-nitro-cGMP. Modern redox biology involves frontiers of cell research and stem cell research; medical and clinical investigations of infections, cancer, metabolic syndrome, aging, and neurodegenerative diseases; and other fields. 8-Nitro-cGMP-mediated signaling and metabolism in cells may therefore be potential targets for drug development, which may lead to discovery of new therapeutic agents for many diseases.", "classifications": [ { "id": "Akaike", "label": "Group Akaike", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Group Nishida", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Shigemoto", "last_name": "Fujii", "name": null }, { "creator_type": "author", "first_name": "Tomohiro", "last_name": "Sawa", "name": null }, { "creator_type": "author", "first_name": "Motohiro", "last_name": "Nishida", "name": null }, { "creator_type": "author", "first_name": "Hideshi", "last_name": "Ihara", "name": null }, { "creator_type": "author", "first_name": "Tomoaki", "last_name": "Ida", "name": null }, { "creator_type": "author", "first_name": "Hozumi", "last_name": "Motohashi", "name": null }, { "creator_type": "author", "first_name": "Takaaki", "last_name": "Akaike", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.abb.2015.11.008" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "27095231" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cysteine", "descriptor_ui": "D003545", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Nucleotides, Cyclic", "descriptor_ui": "D009712", "major_topic": false }, { "descriptor": "Oxidation-Reduction", "descriptor_ui": "D010084", "major_topic": false }, { "descriptor": "Second Messenger Systems", "descriptor_ui": "D015290", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": true }, { "descriptor": "Sulfides", "descriptor_ui": "D013440", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016 Apr 1", "date_precision": "day", "issue": "", "normalized_date": "2016-04-01", "pages": "140-146", "proceedings_title": null, "publisher": "", "title": "Archives of biochemistry and biophysics", "volume": "595", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Redox signaling regulated by an electrophilic cyclic nucleotide and reactive cysteine persulfides.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Cellular populations in both nature and the laboratory are composed of phenotypically heterogeneous individuals that compete with each other resulting in complex population dynamics. Predicting population growth characteristics based on knowledge of heterogeneous single-cell dynamics remains challenging. By observing groups of cells for hundreds of generations at single-cell resolution, we reveal that growth noise causes clonal populations of Escherichia coli to double faster than the mean doubling time of their constituent single cells across a broad set of balanced-growth conditions. We show that the population-level growth rate gain as well as age structures of populations and of cell lineages in competition are predictable. Furthermore, we theoretically reveal that the growth rate gain can be linked with the relative entropy of lineage generation time distributions. Unexpectedly, we find an empirical linear relation between the means and the variances of generation times across conditions, which provides a general constraint on maximal growth rates. Together, these results demonstrate a fundamental benefit of noise for population growth, and identify a growth law that sets a \"speed limit\" for proliferation.", "classifications": [ { "id": "Wakamoto", "label": "Group Wakamoto", "parent": "Wakamoto", "type": "group" }, { "id": "Wakamoto", "label": "Team Wakamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Mikihiro", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Nozoe", "name": null }, { "creator_type": "author", "first_name": "Hidenori", "last_name": "Nakaoka", "name": null }, { "creator_type": "author", "first_name": "Reiko", "last_name": "Okura", "name": null }, { "creator_type": "author", "first_name": "Sayo", "last_name": "Akiyoshi", "name": null }, { "creator_type": "author", "first_name": "Kunihiko", "last_name": "Kaneko", "name": null }, { "creator_type": "author", "first_name": "Edo", "last_name": "Kussell", "name": null }, { "creator_type": "author", "first_name": "Yuichi", "last_name": "Wakamoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1073/pnas.1519412113" }, "pmcid": { "normalized": "PMC4812751" }, "pmid": { "normalized": "26951676" } }, "mesh": [ { "descriptor": "Cell Division", "descriptor_ui": "D002455", "major_topic": true }, { "descriptor": "Microfluidics", "descriptor_ui": "D044085", "major_topic": false }, { "descriptor": "Models, Biological", "descriptor_ui": "D008954", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016 Mar 22", "date_precision": "day", "issue": "12", "normalized_date": "2016-03-22", "pages": "3251-3256", "proceedings_title": null, "publisher": "", "title": "Proceedings of the National Academy of Sciences of the United States of America", "volume": "113", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Noise-driven growth rate gain in clonal cellular populations.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "We propose a model for the spontaneous motion of a droplet induced by inhomogeneity in interfacial tension. The model is derived from a variation of the Lagrangian of the system and we use a time-discretized Morse flow scheme to perform its numerical simulations. Our model can naturally simulate the dynamics of a single droplet, as well as that of multiple droplets, where the volume of each droplet is conserved. We reproduced the ballistic motion and fission of a droplet, and the collision of two droplets was also examined numerically.", "classifications": [ { "id": "Nagayama", "label": "Group Nagayama", "parent": "Fujiwara", "type": "group" }, { "id": "Fujiwara", "label": "Team Fujiwara", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Ken H.", "last_name": "Nagai", "name": null }, { "creator_type": "author", "first_name": "Kunihito", "last_name": "Tachibana", "name": null }, { "creator_type": "author", "first_name": "Yuta", "last_name": "Tobe", "name": null }, { "creator_type": "author", "first_name": "Masaki", "last_name": "Kazama", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Kitahata", "name": null }, { "creator_type": "author", "first_name": "Seiro", "last_name": "Omata", "name": null }, { "creator_type": "author", "first_name": "Masaharu", "last_name": "Nagayama", "name": null } ], "identifiers": { "doi": { "normalized": "10.1063/1.4943582" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "27004893" } }, "mesh": [], "publication": { "conference_name": null, "date": "2016 Mar 21", "date_precision": "day", "issue": "11", "normalized_date": "2016-03-21", "pages": "114707", "proceedings_title": null, "publisher": "", "title": "The Journal of chemical physics", "volume": "144", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Mathematical model for self-propelled droplets driven by interfacial tension.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "A novel platinum-catalyzed cascade cyclization reaction was developed by intramolecular Friedel-Crafts-type C-H coupling of aniline derivatives with a propargyl carbonate unit-allylic amination sequence. Treatment of various propargyl carbonates tethered to meta-aniline derivatives with a Pt(dba)3/DPEphos catalyst system afforded the corresponding 3,4-fused tricyclic 3-alkylidene indolines in 42-99% yield, which were transformed into 3,4-fused indole derivatives by reaction with trifluoroacetic acid. The reaction products exhibited antiproliferative activities against cancer cells, but not normal cells, revealing the potential usefulness of this reaction for medicinal chemistry.", "classifications": [ { "id": "Sodeoka", "label": "Group Sodeoka", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yuta", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Yuito", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Shun-ichi", "last_name": "Nakano", "name": null }, { "creator_type": "author", "first_name": "Kosuke", "last_name": "Dodo", "name": null }, { "creator_type": "author", "first_name": "Natsumi", "last_name": "Yoda", "name": null }, { "creator_type": "author", "first_name": "Ken-Ichi", "last_name": "Shinohara", "name": null }, { "creator_type": "author", "first_name": "Kazuko", "last_name": "Kita", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Kaneda", "name": null }, { "creator_type": "author", "first_name": "Mikiko", "last_name": "Sodeoka", "name": null }, { "creator_type": "author", "first_name": "Yasumasa", "last_name": "Hamada", "name": null }, { "creator_type": "author", "first_name": "Tetsuhiro", "last_name": "Nemoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/chem.201600375" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "26833557" } }, "mesh": [ { "descriptor": "Amination", "descriptor_ui": "D000586", "major_topic": false }, { "descriptor": "Catalysis", "descriptor_ui": "D002384", "major_topic": false }, { "descriptor": "Heterocyclic Compounds, 3-Ring", "descriptor_ui": "D006575", "major_topic": false }, { "descriptor": "Indoles", "descriptor_ui": "D007211", "major_topic": false }, { "descriptor": "Molecular Structure", "descriptor_ui": "D015394", "major_topic": false }, { "descriptor": "Platinum", "descriptor_ui": "D010984", "major_topic": false }, { "descriptor": "Stereoisomerism", "descriptor_ui": "D013237", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016 Mar 18", "date_precision": "day", "issue": "13", "normalized_date": "2016-03-18", "pages": "4418-4421", "proceedings_title": null, "publisher": "", "title": "Chemistry (Weinheim an der Bergstrasse, Germany)", "volume": "22", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Platinum-Catalyzed Friedel-Crafts-Type C-H Coupling-Allylic Amination Cascade to Synthesize 3,4-Fused Tricyclic Indoles.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Central insulin action activates hepatic IL-6/STAT3 signaling, which suppresses the gene expression of hepatic gluconeogenic enzymes. The vagus nerve plays an important role in this centrally mediated hepatic response; however, the precise mechanism underlying this brain-liver interaction is unclear. Here, we present our findings that the vagus nerve suppresses hepatic IL-6/STAT3 signaling via alpha7-nicotinic acetylcholine receptors (alpha7-nAchR) on Kupffer cells, and that central insulin action activates hepatic IL-6/STAT3 signaling by suppressing vagal activity. Indeed, central insulin-mediated hepatic IL-6/STAT3 activation and gluconeogenic gene suppression were impeded in mice with hepatic vagotomy, pharmacological cholinergic blockade, or alpha7-nAchR deficiency. In high-fat diet-induced obese and insulin-resistant mice, control of the vagus nerve by central insulin action was disturbed, inducing a persistent increase of inflammatory cytokines. These findings suggest that dysregulation of the alpha7-nAchR-mediated control of Kupffer cells by central insulin action may affect the pathogenesis of chronic hepatic inflammation in obesity.", "classifications": [ { "id": "Inaba", "label": "Group Inaba", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Kumi", "last_name": "Kimura", "name": null }, { "creator_type": "author", "first_name": "Mamoru", "last_name": "Tanida", "name": null }, { "creator_type": "author", "first_name": "Naoto", "last_name": "Nagata", "name": null }, { "creator_type": "author", "first_name": "Yuka", "last_name": "Inaba", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Mayumi", "last_name": "Nagashimada", "name": null }, { "creator_type": "author", "first_name": "Tsuguhito", "last_name": "Ota", "name": null }, { "creator_type": "author", "first_name": "Shun-ichiro", "last_name": "Asahara", "name": null }, { "creator_type": "author", "first_name": "Yoshiaki", "last_name": "Kido", "name": null }, { "creator_type": "author", "first_name": "Michihiro", "last_name": "Matsumoto", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Toshinai", "name": null }, { "creator_type": "author", "first_name": "Masamitsu", "last_name": "Nakazato", "name": null }, { "creator_type": "author", "first_name": "Toshishige", "last_name": "Shibamoto", "name": null }, { "creator_type": "author", "first_name": "Shuichi", "last_name": "Kaneko", "name": null }, { "creator_type": "author", "first_name": "Masato", "last_name": "Kasuga", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Inoue", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.celrep.2016.02.032" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "26947072" } }, "mesh": [ { "descriptor": "Acetylcholine", "descriptor_ui": "D000109", "major_topic": false }, { "descriptor": "alpha7 Nicotinic Acetylcholine Receptor", "descriptor_ui": "D064569", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Blood Glucose", "descriptor_ui": "D001786", "major_topic": false }, { "descriptor": "Calcium-Binding Proteins", "descriptor_ui": "D002135", "major_topic": false }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Chlorisondamine", "descriptor_ui": "D002714", "major_topic": false }, { "descriptor": "Diet, High-Fat", "descriptor_ui": "D059305", "major_topic": false }, { "descriptor": "Insulin", "descriptor_ui": "D007328", "major_topic": false }, { "descriptor": "Interleukin-6", "descriptor_ui": "D015850", "major_topic": false }, { "descriptor": "Kupffer Cells", "descriptor_ui": "D007728", "major_topic": false }, { "descriptor": "Liver", "descriptor_ui": "D008099", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Nicotine", "descriptor_ui": "D009538", "major_topic": false }, { "descriptor": "Obesity", "descriptor_ui": "D009765", "major_topic": false }, { "descriptor": "Phosphorylation", "descriptor_ui": "D010766", "major_topic": false }, { "descriptor": "Protein Binding", "descriptor_ui": "D011485", "major_topic": false }, { "descriptor": "Receptors, Cell Surface", "descriptor_ui": "D011956", "major_topic": false }, { "descriptor": "Receptors, G-Protein-Coupled", "descriptor_ui": "D043562", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "STAT3 Transcription Factor", "descriptor_ui": "D050796", "major_topic": false }, { "descriptor": "Vagus Nerve", "descriptor_ui": "D014630", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016 Mar 15", "date_precision": "day", "issue": "10", "normalized_date": "2016-03-15", "pages": "2362-2374", "proceedings_title": null, "publisher": "", "title": "Cell reports", "volume": "14", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Central Insulin Action Activates Kupffer Cells by Suppressing Hepatic Vagal Activation via the Nicotinic Alpha 7 Acetylcholine Receptor.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The adsorptive separation of C2H2 and CO2 via porous materials is nontrivial due to the close similarities of their boiling points and kinetic diameters. In this work, we describe a new flexible porous coordination polymer (PCP) [Mn(bdc)(dpe)] (H2bdc = 1,4-benzenedicarboxylic acid, dpe = 1,2-di(4-pyridyl)ethylene) having zero-dimensional pores, which shows an adsorbate discriminatory gate effect. The compound shows gate opening type abrupt adsorption for C2H2 but not for CO2, leading to an appreciable selective adsorption of CO2 over C2H2 at near ambient temperature (273 K). The origin of this unique selectivity, as unveiled by in situ adsorption-X-ray diffraction experiments and density functional theory calculations, is due to vastly different orientations between the phenylene ring of bdc and each gas in the nanopores. The structural change by photochemical transformation of this PCP via [2 + 2] photodimerization leads to the removal of inverse CO2/C2H2 selectivity, verifying the mechanism of the guest discriminatory gate effect.", "classifications": [ { "id": "Hijikata", "label": "Group Hijikata", "parent": "Tsuchiya", "type": "group" }, { "id": "Tsuchiya", "label": "Team Tsuchiya", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Maw Lin", "last_name": "Foo", "name": null }, { "creator_type": "author", "first_name": "Ryotaro", "last_name": "Matsuda", "name": null }, { "creator_type": "author", "first_name": "Yuh", "last_name": "Hijikata", "name": null }, { "creator_type": "author", "first_name": "Rajamani", "last_name": "Krishna", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Horike", "name": null }, { "creator_type": "author", "first_name": "Akihiro", "last_name": "Hori", "name": null }, { "creator_type": "author", "first_name": "Jingui", "last_name": "Duan", "name": null }, { "creator_type": "author", "first_name": "Yohei", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Yoshiki", "last_name": "Kubota", "name": null }, { "creator_type": "author", "first_name": "Masaki", "last_name": "Takata", "name": null }, { "creator_type": "author", "first_name": "Susumu", "last_name": "Kitagawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/jacs.5b10491" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "26876504" } }, "mesh": [], "publication": { "conference_name": null, "date": "2016 Mar 9", "date_precision": "day", "issue": "9", "normalized_date": "2016-03-09", "pages": "3022-3030", "proceedings_title": null, "publisher": "", "title": "Journal of the American Chemical Society", "volume": "138", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "An Adsorbate Discriminatory Gate Effect in a Flexible Porous Coordination Polymer for Selective Adsorption of CO2 over C2H2.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Kawasaki disease (KD) is a systemic vasculitis in infants that develops predominantly in the coronary arteries. Despite the clinically transient nature of active inflammation in childhood albeit rare complications (e.g., coronary artery aneurysm), KD has recently been suggested to increase the incidence of ischemic heart diseases in young adulthood. However, little is known about the histopathology of the coronary artery long after development of the acute KD vasculitis. To address this, we conducted histological studies of rabbit coronary arteries in adolescent phase after induction of the KD-like vasculitis induced by horse serum administration. After a transmural infiltration of inflammatory cells in acute phase at day 7, the artery exhibited a gradual decrease in the number of inflammatory cells and thickening of the intima during the chronic phase up to day 90, where proteoglycans were distinctly accumulated in the intima with abundant involvement of alpha-smooth muscle actin (alpha-SMA)-positive cells, most of which accompanied expression of VCAM-1 and NF-kappaB. Distinct from classical atherosclerosis, inflammatory cells, e.g., macrophages, were barely detected during the chronic phase. These observations indicate that the KD-like coronary arteritis is followed by intimal thickening via accumulation of proteoglycans and proliferation of alpha-SMA-positive cells, reflecting aberrant coronary artery remodeling.", "classifications": [ { "id": "Tanaka", "label": "Group Tanaka", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Maiko", "last_name": "Fujii", "name": null }, { "creator_type": "author", "first_name": "Hideo", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Akihiro", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Chinatsu", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Yoshinori", "last_name": "Harada", "name": null }, { "creator_type": "author", "first_name": "Tetsuro", "last_name": "Takamatsu", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Hamaoka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1267/ahc.15028" }, "pmcid": { "normalized": "PMC4794552" }, "pmid": { "normalized": "27006519" } }, "mesh": [], "publication": { "conference_name": null, "date": "2016 Feb 27", "date_precision": "day", "issue": "1", "normalized_date": "2016-02-27", "pages": "29-36", "proceedings_title": null, "publisher": "", "title": "Acta histochemica et cytochemica", "volume": "49", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Histopathological Characteristics of Post-inflamed Coronary Arteries in Kawasaki Disease-like Vasculitis of Rabbits.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The pathogenesis of amyotrophic lateral sclerosis (ALS) is associated with mutations of Cu,Zn-superoxide dismutase (SOD1), which is a representative antioxidant enzyme. A previous study showed that the denatured apo-form of an ALS-linked mutant of human SOD1, His43 --> Arg (H43R), obtains pro-oxidant activity as the reverse behavior of the native antioxidant activity by rebinding Cu(2+), which is considered to be closely related to the development of ALS. The Cu(2+)-binding site in denatured apo-H43R can be regarded as the center of the pro-oxidant activity, causing cellular oxidative stress. In the present study, the structure of the Cu(2+)-binding site of denatured apo-H43R was investigated to clarify the mechanism of the acquisition of the pro-oxidant activity. His residues constructing the Cu(2+)-binding site in denatured apo-H43R were experimentally assigned by absorption and fluorescence-based assays of SOD1 mutants, in which each of the seven His residues in H43R SOD1 is replaced with Ala. It was found that His120 is not involved with the Cu(2+)-binding site after denaturation, although the other His residues constructing the metal-binding site remain constant after denaturation. The disappearance of His120 from the Cu(2+)-binding site is therefore considered to be one of the important factors in obtaining the pro-oxidant activity. The mechanism of the acquisition of the pro-oxidant activity is discussed based on the results obtained.", "classifications": [ { "id": "Nakabayashi", "label": "Group Nakabayashi", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Nobuhiro", "last_name": "Fujimaki", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Miura", "name": null }, { "creator_type": "author", "first_name": "Takakazu", "last_name": "Nakabayashi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1039/c5cp07729j" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "26791423" } }, "mesh": [ { "descriptor": "Binding Sites", "descriptor_ui": "D001665", "major_topic": false }, { "descriptor": "Hydrogen Bonding", "descriptor_ui": "D006860", "major_topic": false }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": false }, { "descriptor": "Protein Conformation", "descriptor_ui": "D011487", "major_topic": false }, { "descriptor": "Protein Denaturation", "descriptor_ui": "D011489", "major_topic": false }, { "descriptor": "Reactive Oxygen Species", "descriptor_ui": "D017382", "major_topic": false }, { "descriptor": "Superoxide Dismutase", "descriptor_ui": "D013482", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016 Feb 14", "date_precision": "day", "issue": "6", "normalized_date": "2016-02-14", "pages": "4468-4475", "proceedings_title": null, "publisher": "", "title": "Physical chemistry chemical physics : PCCP", "volume": "18", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "The structural analysis of the pro-oxidant copper-binding site of denatured apo-H43R SOD1 and the elucidation of the origin of the acquisition of the pro-oxidant activity.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Inscuteable (Insc) regulates cell fate decisions in several types of stem cells. Although it is recognized that the expression levels of mouse INSC govern the balance between symmetric and asymmetric stem cell division, regulation of mouse Insc gene expression remains poorly understood. Here, we showed that mouse Insc expression transiently increases at an early stage of differentiation, when mouse embryonic stem (mES) cells differentiate into bipotent mesendoderm capable of producing both endoderm and mesoderm in defined culture conditions. We identified the minimum transcriptional regulatory element (354 bases) that drives mouse Insc transcription in mES cells within a region >5 kb upstream of the mouse Insc transcription start site. We found that the transcription factor reticuloendotheliosis oncogene (c-Rel) bound to the minimum element and promoted mouse Insc expression in mES cells. In addition, short interfering RNA-mediated knockdown of either mouse INSC or c-Rel protein decreased mesodermal cell populations without affecting differentiation into the mesendoderm or endoderm. Furthermore, overexpression of mouse INSC rescued the mesoderm-reduced phenotype induced by knockdown of c-Rel. We propose that regulation of mouse Insc expression by c-Rel modulates cell fate decisions during mES cell differentiation.", "classifications": [ { "id": "Toyoshima", "label": "Group Toyoshima", "parent": "Toyoshima", "type": "group" }, { "id": "Toyoshima", "label": "Team Toyoshima", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Riki", "last_name": "Ishibashi", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Kozuki", "name": null }, { "creator_type": "author", "first_name": "Sachiko", "last_name": "Kamakura", "name": null }, { "creator_type": "author", "first_name": "Hideki", "last_name": "Sumimoto", "name": null }, { "creator_type": "author", "first_name": "Fumiko", "last_name": "Toyoshima", "name": null } ], "identifiers": { "doi": { "normalized": "10.1074/jbc.m115.679563" }, "pmcid": { "normalized": "PMC4751378" }, "pmid": { "normalized": "26694615" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Cycle Proteins", "descriptor_ui": "D018797", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": true }, { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "Chromatin Immunoprecipitation", "descriptor_ui": "D047369", "major_topic": false }, { "descriptor": "Endoderm", "descriptor_ui": "D004707", "major_topic": false }, { "descriptor": "Gene Expression Regulation, Developmental", "descriptor_ui": "D018507", "major_topic": true }, { "descriptor": "Genes, Reporter", "descriptor_ui": "D017930", "major_topic": false }, { "descriptor": "Goosecoid Protein", "descriptor_ui": "D051956", "major_topic": false }, { "descriptor": "Luminescent Proteins", "descriptor_ui": "D008164", "major_topic": false }, { "descriptor": "Mesoderm", "descriptor_ui": "D008648", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mouse Embryonic Stem Cells", "descriptor_ui": "D000066450", "major_topic": false }, { "descriptor": "Promoter Regions, Genetic", "descriptor_ui": "D011401", "major_topic": false }, { "descriptor": "Proto-Oncogene Proteins c-rel", "descriptor_ui": "D020569", "major_topic": false }, { "descriptor": "Recombinant Proteins", "descriptor_ui": "D011994", "major_topic": false }, { "descriptor": "Regulatory Elements, Transcriptional", "descriptor_ui": "D050436", "major_topic": false }, { "descriptor": "RNA Interference", "descriptor_ui": "D034622", "major_topic": false }, { "descriptor": "RNA, Small Interfering", "descriptor_ui": "D034741", "major_topic": false }, { "descriptor": "Transcription Initiation Site", "descriptor_ui": "D024363", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016 Feb 12", "date_precision": "day", "issue": "7", "normalized_date": "2016-02-12", "pages": "3333-3345", "proceedings_title": null, "publisher": "", "title": "The Journal of biological chemistry", "volume": "291", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "c-Rel Regulates Inscuteable Gene Expression during Mouse Embryonic Stem Cell Differentiation.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Osteoclasts are specialized polyploid cells that resorb bone. Upon stimulation with receptor activator of nuclear factor-kappaB ligand (RANKL), myeloid precursors commit to becoming polyploid, largely via cell fusion. Polyploidization of osteoclasts is necessary for their bone-resorbing activity, but the mechanisms by which polyploidization is controlled remain to be determined. Here, we demonstrated that in addition to cell fusion, incomplete cytokinesis also plays a role in osteoclast polyploidization. In in vitro cultured osteoclasts derived from mice expressing the fluorescent ubiquitin-based cell cycle indicator (Fucci), RANKL induced polyploidy by incomplete cytokinesis as well as cell fusion. Polyploid cells generated by incomplete cytokinesis had the potential to subsequently undergo cell fusion. Nuclear polyploidy was also observed in osteoclasts in vivo, suggesting the involvement of incomplete cytokinesis in physiological polyploidization. Furthermore, RANKL-induced incomplete cytokinesis was reduced by inhibition of Akt, resulting in impaired multinucleated osteoclast formation. Taken together, these results reveal that RANKL-induced incomplete cytokinesis contributes to polyploidization of osteoclasts via Akt activation.", "classifications": [ { "id": "Sawano", "label": "Group Sawano", "parent": "Shintaku", "type": "group" }, { "id": "Shintaku", "label": "Team Shintaku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Noriko", "last_name": "Takegahara", "name": null }, { "creator_type": "author", "first_name": "Hyunsoo", "last_name": "Kim", "name": null }, { "creator_type": "author", "first_name": "Hiroki", "last_name": "Mizuno", "name": null }, { "creator_type": "author", "first_name": "Asako", "last_name": "Sakaue-Sawano", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Miyawaki", "name": null }, { "creator_type": "author", "first_name": "Michio", "last_name": "Tomura", "name": null }, { "creator_type": "author", "first_name": "Osami", "last_name": "Kanagawa", "name": null }, { "creator_type": "author", "first_name": "Masaru", "last_name": "Ishii", "name": null }, { "creator_type": "author", "first_name": "Yongwon", "last_name": "Choi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1074/jbc.m115.677427" }, "pmcid": { "normalized": "PMC4751386" }, "pmid": { "normalized": "26670608" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Benzimidazoles", "descriptor_ui": "D001562", "major_topic": false }, { "descriptor": "Biomarkers", "descriptor_ui": "D015415", "major_topic": false }, { "descriptor": "Bone Marrow Cells", "descriptor_ui": "D001854", "major_topic": false }, { "descriptor": "Cell Fusion", "descriptor_ui": "D002459", "major_topic": false }, { "descriptor": "Cell Nucleus", "descriptor_ui": "D002467", "major_topic": false }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Crosses, Genetic", "descriptor_ui": "D003433", "major_topic": false }, { "descriptor": "Cytokinesis", "descriptor_ui": "D048749", "major_topic": true }, { "descriptor": "Luminescent Proteins", "descriptor_ui": "D008164", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice, Transgenic", "descriptor_ui": "D008822", "major_topic": false }, { "descriptor": "Myeloid Progenitor Cells", "descriptor_ui": "D023461", "major_topic": false }, { "descriptor": "Osteoclasts", "descriptor_ui": "D010010", "major_topic": false }, { "descriptor": "Osteogenesis", "descriptor_ui": "D010012", "major_topic": false }, { "descriptor": "Osteolysis", "descriptor_ui": "D010014", "major_topic": false }, { "descriptor": "Phosphorylation", "descriptor_ui": "D010766", "major_topic": false }, { "descriptor": "Polyploidy", "descriptor_ui": "D011123", "major_topic": true }, { "descriptor": "Protein Processing, Post-Translational", "descriptor_ui": "D011499", "major_topic": false }, { "descriptor": "Proto-Oncogene Proteins c-akt", "descriptor_ui": "D051057", "major_topic": false }, { "descriptor": "Quinoxalines", "descriptor_ui": "D011810", "major_topic": false }, { "descriptor": "RANK Ligand", "descriptor_ui": "D053245", "major_topic": false }, { "descriptor": "Recombinant Fusion Proteins", "descriptor_ui": "D011993", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016 Feb 12", "date_precision": "day", "issue": "7", "normalized_date": "2016-02-12", "pages": "3439-3454", "proceedings_title": null, "publisher": "", "title": "The Journal of biological chemistry", "volume": "291", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Involvement of Receptor Activator of Nuclear Factor-kappaB Ligand (RANKL)-induced Incomplete Cytokinesis in the Polyploidization of Osteoclasts.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Women with epithelial ovarian cancer (EOC) are usually treated with platinum/taxane therapy after cytoreductive surgery but there is considerable inter-individual variation in response. To identify germline single-nucleotide polymorphisms (SNPs) that contribute to variations in individual responses to chemotherapy, we carried out a multi-phase genome-wide association study (GWAS) in 1,244 women diagnosed with serous EOC who were treated with the same first-line chemotherapy, carboplatin and paclitaxel. We identified two SNPs (rs7874043 and rs72700653) in TTC39B (best P=7x10-5, HR=1.90, for rs7874043) associated with progression-free survival (PFS). Functional analyses show that both SNPs lie in a putative regulatory element (PRE) that physically interacts with the promoters of PSIP1, CCDC171 and an alternative promoter of TTC39B. The C allele of rs7874043 is associated with poor PFS and showed increased binding of the Sp1 transcription factor, which is critical for chromatin interactions with PSIP1. Silencing of PSIP1 significantly impaired DNA damage-induced Rad51 nuclear foci and reduced cell viability in ovarian cancer lines. PSIP1 (PC4 and SFRS1 Interacting Protein 1) is known to protect cells from stress-induced apoptosis, and high expression is associated with poor PFS in EOC patients. We therefore suggest that the minor allele of rs7874043 confers poor PFS by increasing PSIP1 expression.", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Juliet D.", "last_name": "French", "name": null }, { "creator_type": "author", "first_name": "Sharon E.", "last_name": "Johnatty", "name": null }, { "creator_type": "author", "first_name": "Yi", "last_name": "Lu", "name": null }, { "creator_type": "author", "first_name": "Jonathan", "last_name": "Beesley", "name": null }, { "creator_type": "author", "first_name": "Bo", "last_name": "Gao", "name": null }, { "creator_type": "author", "first_name": "Murugan", "last_name": "Kalimutho", "name": null }, { "creator_type": "author", "first_name": "Michelle J.", "last_name": "Henderson", "name": null }, { "creator_type": "author", "first_name": "Amanda J.", "last_name": "Russell", "name": null }, { "creator_type": "author", "first_name": "Siddhartha", "last_name": "Kar", "name": null }, { "creator_type": "author", "first_name": "Xiaoqing", "last_name": "Chen", "name": null }, { "creator_type": "author", "first_name": "Kristine M.", "last_name": "Hillman", "name": null }, { "creator_type": "author", "first_name": "Susanne", "last_name": "Kaufmann", "name": null }, { "creator_type": "author", "first_name": "Haran", "last_name": "Sivakumaran", "name": null }, { "creator_type": "author", "first_name": "Martin", "last_name": "O'Reilly", "name": null }, { "creator_type": "author", "first_name": "Chen", "last_name": "Wang", "name": null }, { "creator_type": "author", "first_name": "Darren J.", "last_name": "Korbie", "name": null }, { "creator_type": "author", "first_name": "Diether", "last_name": "Lambrechts", "name": null }, { "creator_type": "author", "first_name": "Evelyn", "last_name": "Despierre", "name": null }, { "creator_type": "author", "first_name": "Els", "last_name": "Van Nieuwenhuysen", "name": null }, { "creator_type": "author", "first_name": "Sandrina", "last_name": "Lambrechts", "name": null }, { "creator_type": "author", "first_name": "Ignace", "last_name": "Vergote", "name": null }, { "creator_type": "author", "first_name": "Beth", "last_name": "Karlan", "name": null }, { "creator_type": "author", "first_name": "Jenny", "last_name": "Lester", "name": null }, { "creator_type": "author", "first_name": "Sandra", "last_name": "Orsulic", "name": null }, { "creator_type": "author", "first_name": "Christine", "last_name": "Walsh", "name": null }, { "creator_type": "author", "first_name": "Peter A.", "last_name": "Fasching", "name": null }, { "creator_type": "author", "first_name": "Matthias W.", "last_name": "Beckmann", "name": null }, { "creator_type": "author", "first_name": "Arif B.", "last_name": "Ekici", "name": null }, { "creator_type": "author", "first_name": "Alexander", "last_name": "Hein", "name": null }, { "creator_type": "author", "first_name": "Keitaro", "last_name": "Matsuo", "name": null }, { "creator_type": "author", "first_name": "Satoyo", "last_name": "Hosono", "name": null }, { "creator_type": "author", "first_name": "Jacobus", "last_name": "Pisterer", "name": null }, { "creator_type": "author", "first_name": "Peter", "last_name": "Hillemanns", "name": null }, { "creator_type": "author", "first_name": "Toru", "last_name": "Nakanishi", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null }, { "creator_type": "author", "first_name": "Marc T.", "last_name": "Goodman", "name": null }, { "creator_type": "author", "first_name": "Galina", "last_name": "Lurie", "name": null }, { "creator_type": "author", "first_name": "Rayna K.", "last_name": "Matsuno", "name": null }, { "creator_type": "author", "first_name": "Pamela J.", "last_name": "Thompson", "name": null }, { "creator_type": "author", "first_name": "Tanja", "last_name": "Pejovic", "name": null }, { "creator_type": "author", "first_name": "Yukie", "last_name": "Bean", "name": null }, { "creator_type": "author", "first_name": "Florian", "last_name": "Heitz", "name": null }, { "creator_type": "author", "first_name": "Philipp", "last_name": "Harter", "name": null }, { "creator_type": "author", "first_name": "Andreas", "last_name": "du Bois", "name": null }, { "creator_type": "author", "first_name": "Ira", "last_name": "Schwaab", "name": null }, { "creator_type": "author", "first_name": "Estrid", "last_name": "Hogdall", "name": null }, { "creator_type": "author", "first_name": "Susanne K.", "last_name": "Kjaer", "name": null }, { "creator_type": "author", "first_name": "Allan", "last_name": "Jensen", "name": null }, { "creator_type": "author", "first_name": "Claus", "last_name": "Hogdall", "name": null }, { "creator_type": "author", "first_name": "Lene", "last_name": "Lundvall", "name": null }, { "creator_type": "author", "first_name": "Svend Aage", "last_name": "Engelholm", "name": null }, { "creator_type": "author", "first_name": "Bob", "last_name": "Brown", "name": null }, { "creator_type": "author", "first_name": "James M.", "last_name": "Flanagan", "name": null }, { "creator_type": "author", "first_name": "Michelle D.", "last_name": "Metcalf", "name": null }, { "creator_type": "author", "first_name": "Nadeem", "last_name": "Siddiqui", "name": null }, { "creator_type": "author", "first_name": "Thomas", "last_name": "Sellers", "name": null }, { "creator_type": "author", "first_name": "Brooke", "last_name": "Fridley", "name": null }, { "creator_type": "author", "first_name": "Julie", "last_name": "Cunningham", "name": null }, { "creator_type": "author", "first_name": "Joellen M.", "last_name": "Schildkraut", "name": null }, { "creator_type": "author", "first_name": "Ed", "last_name": "Iversen", "name": null }, { "creator_type": "author", "first_name": "Rachel Palmieri", "last_name": "Weber", "name": null }, { "creator_type": "author", "first_name": "Donal", "last_name": "Brennan", "name": null }, { "creator_type": "author", "first_name": "Andrew", "last_name": "Berchuck", "name": null }, { "creator_type": "author", "first_name": "Paul", "last_name": "Pharoah", "name": null }, { "creator_type": "author", "first_name": "Paul", "last_name": "Harnett", "name": null }, { "creator_type": "author", "first_name": "Murray D.", "last_name": "Norris", "name": null }, { "creator_type": "author", "first_name": "Michelle", "last_name": "Haber", "name": null }, { "creator_type": "author", "first_name": "Ellen L.", "last_name": "Goode", "name": null }, { "creator_type": "author", "first_name": "Jason S.", "last_name": "Lee", "name": null }, { "creator_type": "author", "first_name": "Kum Kum", "last_name": "Khanna", "name": null }, { "creator_type": "author", "first_name": "Kerstin B.", "last_name": "Meyer", "name": null }, { "creator_type": "author", "first_name": "Georgia", "last_name": "Chenevix-Trench", "name": null }, { "creator_type": "author", "first_name": "Anna", "last_name": "deFazio", "name": null }, { "creator_type": "author", "first_name": "Stacey L.", "last_name": "Edwards", "name": null }, { "creator_type": "author", "first_name": "Stuart", "last_name": "MacGregor", "name": null } ], "identifiers": { "doi": { "normalized": "10.18632/oncotarget.7047" }, "pmcid": { "normalized": "PMC4872719" }, "pmid": { "normalized": "26840454" } }, "mesh": [ { "descriptor": "Adaptor Proteins, Signal Transducing", "descriptor_ui": "D048868", "major_topic": false }, { "descriptor": "Apoptosis", "descriptor_ui": "D017209", "major_topic": false }, { "descriptor": "Biomarkers, Tumor", "descriptor_ui": "D014408", "major_topic": false }, { "descriptor": "Cell Proliferation", "descriptor_ui": "D049109", "major_topic": false }, { "descriptor": "Chromatin Immunoprecipitation", "descriptor_ui": "D047369", "major_topic": false }, { "descriptor": "Cohort Studies", "descriptor_ui": "D015331", "major_topic": false }, { "descriptor": "Cystadenocarcinoma, Serous", "descriptor_ui": "D018284", "major_topic": false }, { "descriptor": "Electrophoretic Mobility Shift Assay", "descriptor_ui": "D024202", "major_topic": false }, { "descriptor": "Enhancer Elements, Genetic", "descriptor_ui": "D004742", "major_topic": false }, { "descriptor": "Fallopian Tube Neoplasms", "descriptor_ui": "D005185", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Follow-Up Studies", "descriptor_ui": "D005500", "major_topic": false }, { "descriptor": "Germ-Line Mutation", "descriptor_ui": "D018095", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Ovarian Neoplasms", "descriptor_ui": "D010051", "major_topic": false }, { "descriptor": "Peritoneal Neoplasms", "descriptor_ui": "D010534", "major_topic": false }, { "descriptor": "Polymorphism, Single Nucleotide", "descriptor_ui": "D020641", "major_topic": false }, { "descriptor": "Prognosis", "descriptor_ui": "D011379", "major_topic": false }, { "descriptor": "Real-Time Polymerase Chain Reaction", "descriptor_ui": "D060888", "major_topic": false }, { "descriptor": "Reverse Transcriptase Polymerase Chain Reaction", "descriptor_ui": "D020133", "major_topic": false }, { "descriptor": "RNA, Messenger", "descriptor_ui": "D012333", "major_topic": false }, { "descriptor": "Survival Rate", "descriptor_ui": "D015996", "major_topic": false }, { "descriptor": "Transcription Factors", "descriptor_ui": "D014157", "major_topic": false }, { "descriptor": "Tumor Cells, Cultured", "descriptor_ui": "D014407", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016 Feb 9", "date_precision": "day", "issue": "6", "normalized_date": "2016-02-09", "pages": "6353-6368", "proceedings_title": null, "publisher": "", "title": "Oncotarget", "volume": "7", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Germline polymorphisms in an enhancer of PSIP1 are associated with progression-free survival in epithelial ovarian cancer.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "8-Nitroguanosine 3',5'-cyclic monophosphate (8-nitro-cGMP) is a nitrated derivative of guanosine 3',5'-cyclic monophosphate (cGMP) formed endogenously under conditions associated with production of both reactive oxygen species and nitric oxide. It acts as an electrophilic second messenger in the regulation of cellular signaling by inducing a post-translational modification of redox-sensitive protein thiols via covalent adduction of cGMP moieties to protein thiols (protein S-guanylation). Here, we demonstrate that 8-nitro-cGMP potentially S-guanylates thiol groups of cGMP-dependent protein kinase (PKG), the enzyme that serves as one of the major receptor proteins for intracellular cGMP and controls a variety of cellular responses. S-Guanylation of PKG was found to occur in a site specific manner; Cys42 and Cys195 were the susceptible residues among 11 Cys residues. Importantly, S-guanylation at Cys195, which is located in the high-affinity cGMP binding domain of PKG, causes persistent enzyme activation as determined by in vitro kinase assay as well as by an organ bath assay. In vivo, S-guanylation of PKG was demonstrated to occur in mice without any specific treatment and was significantly enhanced by lipopolysaccharide administration. These findings warrant further investigation in terms of the physiological and pathophysiological roles of S-guanylation-dependent persistent PKG activation.", "classifications": [ { "id": "Akaike", "label": "Group Akaike", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Soichiro", "last_name": "Akashi", "name": null }, { "creator_type": "author", "first_name": "Khandaker Ahtesham", "last_name": "Ahmed", "name": null }, { "creator_type": "author", "first_name": "Tomohiro", "last_name": "Sawa", "name": null }, { "creator_type": "author", "first_name": "Katsuhiko", "last_name": "Ono", "name": null }, { "creator_type": "author", "first_name": "Hiroyasu", "last_name": "Tsutsuki", "name": null }, { "creator_type": "author", "first_name": "Joseph R.", "last_name": "Burgoyne", "name": null }, { "creator_type": "author", "first_name": "Tomoaki", "last_name": "Ida", "name": null }, { "creator_type": "author", "first_name": "Eiji", "last_name": "Horio", "name": null }, { "creator_type": "author", "first_name": "Oleksandra", "last_name": "Prysyazhna", "name": null }, { "creator_type": "author", "first_name": "Yuichi", "last_name": "Oike", "name": null }, { "creator_type": "author", "first_name": "Mizanur Md", "last_name": "Rahaman", "name": null }, { "creator_type": "author", "first_name": "Philip", "last_name": "Eaton", "name": null }, { "creator_type": "author", "first_name": "Shigemoto", "last_name": "Fujii", "name": null }, { "creator_type": "author", "first_name": "Takaaki", "last_name": "Akaike", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/acs.biochem.5b00774" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "26784639" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cyclic GMP-Dependent Protein Kinases", "descriptor_ui": "D017869", "major_topic": false }, { "descriptor": "Enzyme Activation", "descriptor_ui": "D004789", "major_topic": false }, { "descriptor": "Guanine", "descriptor_ui": "D006147", "major_topic": false }, { "descriptor": "In Vitro Techniques", "descriptor_ui": "D066298", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Myocardium", "descriptor_ui": "D009206", "major_topic": false }, { "descriptor": "Nucleotides, Cyclic", "descriptor_ui": "D009712", "major_topic": false }, { "descriptor": "Proteins", "descriptor_ui": "D011506", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016 Feb 9", "date_precision": "day", "issue": "5", "normalized_date": "2016-02-09", "pages": "751-761", "proceedings_title": null, "publisher": "", "title": "Biochemistry", "volume": "55", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Persistent Activation of cGMP-Dependent Protein Kinase by a Nitrated Cyclic Nucleotide via Site Specific Protein S-Guanylation.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Restriction-modification (RM) systems represent a minimal and ubiquitous biological system of self/non-self discrimination in prokaryotes [1], which protects hosts from exogenous DNA [2]. The mechanism is based on the balance between methyltransferase (M) and cognate restriction endonuclease (R). M tags endogenous DNA as self by methylating short specific DNA sequences called restriction sites, whereas R recognizes unmethylated restriction sites as non-self and introduces a double-stranded DNA break [3]. Restriction sites are significantly underrepresented in prokaryotic genomes [4-7], suggesting that the discrimination mechanism is imperfect and occasionally leads to autoimmunity due to self-DNA cleavage (self-restriction) [8]. Furthermore, RM systems can promote DNA recombination [9] and contribute to genetic variation in microbial populations, thus facilitating adaptive evolution [10]. However, cleavage of self-DNA by RM systems as elements shaping prokaryotic genomes has not been directly detected, and its cause, frequency, and outcome are unknown. We quantify self-restriction caused by two RM systems of Escherichia coli and find that, in agreement with levels of restriction site avoidance, EcoRI, but not EcoRV, cleaves self-DNA at a measurable rate. Self-restriction is a stochastic process, which temporarily induces the SOS response, and is followed by DNA repair, maintaining cell viability. We find that RM systems with higher restriction efficiency against bacteriophage infections exhibit a higher rate of self-restriction, and that this rate can be further increased by stochastic imbalance between R and M. Our results identify molecular noise in RM systems as a factor shaping prokaryotic genomes.", "classifications": [ { "id": "Wakamoto", "label": "Group Wakamoto", "parent": "Wakamoto", "type": "group" }, { "id": "Wakamoto", "label": "Team Wakamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Maros", "last_name": "Pleska", "name": null }, { "creator_type": "author", "first_name": "Long", "last_name": "Qian", "name": null }, { "creator_type": "author", "first_name": "Reiko", "last_name": "Okura", "name": null }, { "creator_type": "author", "first_name": "Tobias", "last_name": "Bergmiller", "name": null }, { "creator_type": "author", "first_name": "Yuichi", "last_name": "Wakamoto", "name": null }, { "creator_type": "author", "first_name": "Edo", "last_name": "Kussell", "name": null }, { "creator_type": "author", "first_name": "Calin C.", "last_name": "Guet", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.cub.2015.12.041" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "26804559" } }, "mesh": [ { "descriptor": "Autoimmunity", "descriptor_ui": "D015551", "major_topic": true }, { "descriptor": "Bacteriophages", "descriptor_ui": "D001435", "major_topic": false }, { "descriptor": "DNA Repair", "descriptor_ui": "D004260", "major_topic": false }, { "descriptor": "DNA Restriction-Modification Enzymes", "descriptor_ui": "D015280", "major_topic": true }, { "descriptor": "Escherichia coli", "descriptor_ui": "D004926", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016 Feb 8", "date_precision": "day", "issue": "3", "normalized_date": "2016-02-08", "pages": "404-409", "proceedings_title": null, "publisher": "", "title": "Current biology : CB", "volume": "26", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Bacterial Autoimmunity Due to a Restriction-Modification System.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Genome-wide association studies (GWAS) of lung cancer in Asian never-smoking women have previously identified six susceptibility loci associated with lung cancer risk. To further discover new susceptibility loci, we imputed data from four GWAS of Asian non-smoking female lung cancer (6877 cases and 6277 controls) using the 1000 Genomes Project (Phase 1 Release 3) data as the reference and genotyped additional samples (5878 cases and 7046 controls) for possible replication. In our meta-analysis, three new loci achieved genome-wide significance, marked by single nucleotide polymorphism (SNP) rs7741164 at 6p21.1 (per-allele odds ratio (OR) = 1.17; P = 5.8 x 10(-13)), rs72658409 at 9p21.3 (per-allele OR = 0.77; P = 1.41 x 10(-10)) and rs11610143 at 12q13.13 (per-allele OR = 0.89; P = 4.96 x 10(-9)). These findings identified new genetic susceptibility alleles for lung cancer in never-smoking women in Asia and merit follow-up to understand their biological underpinnings.", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Zhaoming", "last_name": "Wang", "name": null }, { "creator_type": "author", "first_name": "Wei Jie", "last_name": "Seow", "name": null }, { "creator_type": "author", "first_name": "Kouya", "last_name": "Shiraishi", "name": null }, { "creator_type": "author", "first_name": "Chao A.", "last_name": "Hsiung", "name": null }, { "creator_type": "author", "first_name": "Keitaro", "last_name": "Matsuo", "name": null }, { "creator_type": "author", "first_name": "Jie", "last_name": "Liu", "name": null }, { "creator_type": "author", "first_name": "Kexin", "last_name": "Chen", "name": null }, { "creator_type": "author", "first_name": "Taiki", "last_name": "Yamji", "name": null }, { "creator_type": "author", "first_name": "Yang", "last_name": "Yang", "name": null }, { "creator_type": "author", "first_name": "I.-Shou", "last_name": "Chang", "name": null }, { "creator_type": "author", "first_name": "Chen", "last_name": "Wu", "name": null }, { "creator_type": "author", "first_name": "Yun-Chul", "last_name": "Hong", "name": null }, { "creator_type": "author", "first_name": "Laurie", "last_name": "Burdett", "name": null }, { "creator_type": "author", "first_name": "Kathleen", "last_name": "Wyatt", "name": null }, { "creator_type": "author", "first_name": "Charles C.", "last_name": "Chung", "name": null }, { "creator_type": "author", "first_name": "Shengchao A.", "last_name": "Li", "name": null }, { "creator_type": "author", "first_name": "Meredith", "last_name": "Yeager", "name": null }, { "creator_type": "author", "first_name": "Amy", "last_name": "Hutchinson", "name": null }, { "creator_type": "author", "first_name": "Wei", "last_name": "Hu", "name": null }, { "creator_type": "author", "first_name": "Neil", "last_name": "Caporaso", "name": null }, { "creator_type": "author", "first_name": "Maria T.", "last_name": "Landi", "name": null }, { "creator_type": "author", "first_name": "Nilanjan", "last_name": "Chatterjee", "name": null }, { "creator_type": "author", "first_name": "Minsun", "last_name": "Song", "name": null }, { "creator_type": "author", "first_name": "Joseph F. Jr", "last_name": "Fraumeni", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Kohno", "name": null }, { "creator_type": "author", "first_name": "Jun", "last_name": "Yokota", "name": null }, { "creator_type": "author", "first_name": "Hideo", "last_name": "Kunitoh", "name": null }, { "creator_type": "author", "first_name": "Kyota", "last_name": "Ashikawa", "name": null }, { "creator_type": "author", "first_name": "Yukihide", "last_name": "Momozawa", "name": null }, { "creator_type": "author", "first_name": "Yataro", "last_name": "Daigo", "name": null }, { "creator_type": "author", "first_name": "Tetsuya", "last_name": "Mitsudomi", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null }, { "creator_type": "author", "first_name": "Toyoaki", "last_name": "Hida", "name": null }, { "creator_type": "author", "first_name": "Zhibin", "last_name": "Hu", "name": null }, { "creator_type": "author", "first_name": "Juncheng", "last_name": "Dai", "name": null }, { "creator_type": "author", "first_name": "Hongxia", "last_name": "Ma", "name": null }, { "creator_type": "author", "first_name": "Guangfu", "last_name": "Jin", "name": null }, { "creator_type": "author", "first_name": "Bao", "last_name": "Song", "name": null }, { "creator_type": "author", "first_name": "Zhehai", "last_name": "Wang", "name": null }, { "creator_type": "author", "first_name": "Sensen", "last_name": "Cheng", "name": null }, { "creator_type": "author", "first_name": "Zhihua", "last_name": "Yin", "name": null }, { "creator_type": "author", "first_name": "Xuelian", "last_name": "Li", "name": null }, { "creator_type": "author", "first_name": "Yangwu", "last_name": "Ren", "name": null }, { "creator_type": "author", "first_name": "Peng", "last_name": "Guan", "name": null }, { "creator_type": "author", "first_name": "Jiang", "last_name": "Chang", "name": null }, { "creator_type": "author", "first_name": "Wen", "last_name": "Tan", "name": null }, { "creator_type": "author", "first_name": "Chien-Jen", "last_name": "Chen", "name": null }, { "creator_type": "author", "first_name": "Gee-Chen", "last_name": "Chang", "name": null }, { "creator_type": "author", "first_name": "Ying-Huang", "last_name": "Tsai", "name": null }, { "creator_type": "author", "first_name": "Wu-Chou", "last_name": "Su", "name": null }, { "creator_type": "author", "first_name": "Kuan-Yu", "last_name": "Chen", "name": null }, { "creator_type": "author", "first_name": "Ming-Shyan", "last_name": "Huang", "name": null }, { "creator_type": "author", "first_name": "Yuh-Min", "last_name": "Chen", "name": null }, { "creator_type": "author", "first_name": "Hong", "last_name": "Zheng", "name": null }, { "creator_type": "author", "first_name": "Haixin", "last_name": "Li", "name": null }, { "creator_type": "author", "first_name": "Ping", "last_name": "Cui", "name": null }, { "creator_type": "author", "first_name": "Huan", "last_name": "Guo", "name": null 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"creator_type": "author", "first_name": "Young-Chul", "last_name": "Kim", "name": null }, { "creator_type": "author", "first_name": "Sook Whan", "last_name": "Sung", "name": null }, { "creator_type": "author", "first_name": "Jun Suk", "last_name": "Kim", "name": null }, { "creator_type": "author", "first_name": "Ho-Il", "last_name": "Yoon", "name": null }, { "creator_type": "author", "first_name": "Sun-Seog", "last_name": "Kweon", "name": null }, { "creator_type": "author", "first_name": "Min-Ho", "last_name": "Shin", "name": null }, { "creator_type": "author", "first_name": "Adeline", "last_name": "Seow", "name": null }, { "creator_type": "author", "first_name": "Ying", "last_name": "Chen", "name": null }, { "creator_type": "author", "first_name": "Wei-Yen", "last_name": "Lim", "name": null }, { "creator_type": "author", "first_name": "Jianjun", "last_name": "Liu", "name": null }, { "creator_type": "author", "first_name": "Maria Pik", "last_name": "Wong", "name": null }, { "creator_type": "author", "first_name": "Victor Ho Fun", "last_name": "Lee", "name": null }, { "creator_type": "author", "first_name": "Bryan A.", "last_name": "Bassig", "name": null }, { "creator_type": "author", "first_name": "Margaret", "last_name": "Tucker", "name": null }, { "creator_type": "author", "first_name": "Sonja I.", "last_name": "Berndt", "name": null }, { "creator_type": "author", "first_name": "Wong-Ho", "last_name": "Chow", "name": null }, { "creator_type": "author", "first_name": "Bu-Tian", "last_name": "Ji", "name": null }, { "creator_type": "author", "first_name": "Junwen", "last_name": "Wang", "name": null }, { "creator_type": "author", "first_name": "Jun", "last_name": "Xu", "name": null }, { "creator_type": "author", "first_name": "Alan Dart Loon", "last_name": "Sihoe", "name": null }, { "creator_type": "author", "first_name": "James C. M.", "last_name": "Ho", "name": null }, { "creator_type": "author", "first_name": "John K. C.", "last_name": "Chan", "name": null }, { "creator_type": "author", "first_name": "Jiu-Cun", "last_name": "Wang", "name": null }, { "creator_type": "author", "first_name": "Daru", "last_name": "Lu", "name": null }, { "creator_type": "author", "first_name": "Xueying", "last_name": "Zhao", "name": null }, { "creator_type": "author", "first_name": "Zhenhong", "last_name": "Zhao", "name": null }, { "creator_type": "author", "first_name": "Junjie", "last_name": "Wu", "name": null }, { "creator_type": "author", "first_name": "Hongyan", "last_name": "Chen", "name": null }, { "creator_type": "author", "first_name": "Li", "last_name": "Jin", "name": null }, { "creator_type": "author", "first_name": "Fusheng", "last_name": "Wei", "name": null }, { "creator_type": "author", "first_name": "Guoping", "last_name": "Wu", "name": null }, { "creator_type": "author", "first_name": "She-Juan", "last_name": "An", "name": null }, { "creator_type": "author", "first_name": "Xu-Chao", "last_name": "Zhang", "name": null }, { "creator_type": "author", "first_name": "Jian", "last_name": "Su", "name": null }, { "creator_type": "author", "first_name": "Yi-Long", "last_name": "Wu", "name": null }, { "creator_type": "author", "first_name": "Yu-Tang", "last_name": "Gao", "name": null }, { "creator_type": "author", "first_name": "Yong-Bing", "last_name": "Xiang", "name": null }, { "creator_type": "author", "first_name": "Xingzhou", "last_name": "He", "name": null }, { "creator_type": "author", "first_name": "Jihua", "last_name": "Li", "name": null }, { "creator_type": "author", "first_name": "Wei", "last_name": "Zheng", "name": null }, { "creator_type": "author", "first_name": "Xiao-Ou", "last_name": "Shu", "name": null }, { "creator_type": "author", "first_name": "Qiuyin", "last_name": "Cai", "name": null }, { "creator_type": "author", "first_name": "Robert", "last_name": "Klein", "name": null }, { "creator_type": "author", "first_name": "William", "last_name": "Pao", "name": null }, { "creator_type": "author", "first_name": "Charles", "last_name": "Lawrence", "name": null }, { "creator_type": "author", "first_name": "H. Dean 3rd", "last_name": "Hosgood", "name": null }, { "creator_type": "author", "first_name": "Chin-Fu", "last_name": "Hsiao", "name": null }, { "creator_type": "author", "first_name": "Li-Hsin", "last_name": "Chien", "name": null }, { "creator_type": "author", "first_name": "Ying-Hsiang", "last_name": "Chen", "name": null }, { "creator_type": "author", "first_name": "Chung-Hsing", "last_name": "Chen", "name": null }, { "creator_type": "author", "first_name": "Wen-Chang", "last_name": "Wang", "name": null }, { "creator_type": "author", "first_name": "Chih-Yi", "last_name": "Chen", "name": null }, { "creator_type": "author", "first_name": "Chih-Liang", "last_name": "Wang", "name": null }, { "creator_type": "author", "first_name": "Chong-Jen", "last_name": "Yu", "name": null }, { "creator_type": "author", "first_name": "Hui-Ling", "last_name": "Chen", "name": null }, { "creator_type": "author", "first_name": "Yu-Chun", "last_name": "Su", "name": null }, { "creator_type": "author", "first_name": "Fang-Yu", "last_name": "Tsai", "name": null }, { "creator_type": "author", "first_name": "Yi-Song", "last_name": "Chen", "name": null }, { "creator_type": "author", "first_name": "Yao-Jen", "last_name": "Li", "name": null }, { "creator_type": "author", "first_name": "Tsung-Ying", "last_name": "Yang", "name": null }, { "creator_type": "author", "first_name": "Chien-Chung", "last_name": "Lin", "name": null }, { "creator_type": "author", "first_name": "Pan-Chyr", "last_name": "Yang", "name": null }, { "creator_type": "author", "first_name": "Tangchun", "last_name": "Wu", "name": null }, { "creator_type": "author", "first_name": "Dongxin", "last_name": "Lin", "name": null }, { "creator_type": "author", "first_name": "Baosen", "last_name": "Zhou", "name": null }, { "creator_type": "author", "first_name": "Jinming", "last_name": "Yu", "name": null }, { "creator_type": "author", "first_name": "Hongbing", "last_name": "Shen", "name": null }, { "creator_type": "author", "first_name": "Michiaki", "last_name": "Kubo", "name": null }, { "creator_type": "author", "first_name": "Stephen J.", "last_name": "Chanock", "name": null }, { "creator_type": "author", "first_name": "Nathaniel", "last_name": "Rothman", "name": null }, { "creator_type": "author", "first_name": "Qing", "last_name": "Lan", "name": null } ], "identifiers": { "doi": { "normalized": "10.1093/hmg/ddv494" }, "pmcid": { "normalized": "PMC4731021" }, "pmid": { "normalized": "26732429" } }, "mesh": [ { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Alleles", "descriptor_ui": "D000483", "major_topic": false }, { "descriptor": "Asian People", "descriptor_ui": "D044466", "major_topic": false }, { "descriptor": "Case-Control Studies", "descriptor_ui": "D016022", "major_topic": false }, { "descriptor": "Chromosomes, Human, Pair 12", "descriptor_ui": "D002881", "major_topic": false }, { "descriptor": "Chromosomes, Human, Pair 6", "descriptor_ui": "D002896", "major_topic": false }, { "descriptor": "Chromosomes, Human, Pair 9", "descriptor_ui": "D002899", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Genetic Loci", "descriptor_ui": "D056426", "major_topic": true }, { "descriptor": "Genetic Predisposition to Disease", "descriptor_ui": "D020022", "major_topic": true }, { "descriptor": "Genome-Wide Association Study", "descriptor_ui": "D055106", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Lung Neoplasms", "descriptor_ui": "D008175", "major_topic": false }, { "descriptor": "Odds Ratio", "descriptor_ui": "D016017", "major_topic": false }, { "descriptor": "Polymorphism, Single Nucleotide", "descriptor_ui": "D020641", "major_topic": true }, { "descriptor": "Smoking", "descriptor_ui": "D012907", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016 Feb 1", "date_precision": "day", "issue": "3", "normalized_date": "2016-02-01", "pages": "620-629", "proceedings_title": null, "publisher": "", "title": "Human molecular genetics", "volume": "25", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Meta-analysis of genome-wide association studies identifies multiple lung cancer susceptibility loci in never-smoking Asian women.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Phospha-fluorescein (POF), a phosphine oxide-containing analogue of fluorescein, was synthesized and its photophysical properties were examined. Compared with fluorescein and sila-fluorescein, POF displayed significantly red-shifted absorption and fluorescence as well as superior photobleaching resistance, while retaining the pH-responsive characteristics of fluorescein dyes.", "classifications": [ { "id": "Sato", "label": "Group Sato", "parent": "Tsuchiya", "type": "group" }, { "id": "Tsuchiya", "label": "Team Tsuchiya", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Aiko", "last_name": "Fukazawa", "name": null }, { "creator_type": "author", "first_name": "Shinji", "last_name": "Suda", "name": null }, { "creator_type": "author", "first_name": "Masayasu", "last_name": "Taki", "name": null }, { "creator_type": "author", "first_name": "Eriko", "last_name": "Yamaguchi", "name": null }, { "creator_type": "author", "first_name": "Marek", "last_name": "Grzybowski", "name": null }, { "creator_type": "author", "first_name": "Yoshikatsu", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Tetsuya", "last_name": "Higashiyama", "name": null }, { "creator_type": "author", "first_name": "Shigehiro", "last_name": "Yamaguchi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1039/c5cc09345g" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "26617335" } }, "mesh": [], "publication": { "conference_name": null, "date": "2016 Jan 21", "date_precision": "day", "issue": "6", "normalized_date": "2016-01-21", "pages": "1120-1123", "proceedings_title": null, "publisher": "", "title": "Chemical communications (Cambridge, England)", "volume": "52", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Phospha-fluorescein: a red-emissive fluorescein analogue with high photobleaching resistance.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Photodynamic diagnosis based on 5-aminolevulinic acid-induced protoporphyrin IX has been clinically applied in many fields based upon its evidenced efficacy and adequate safety. In order to establish a personalized medicine approach for treating gastric cancer patients, rapid intraoperative detection of malignant lesions has become important. Feasibility of photodynamic diagnosis using 5-aminolevulinic acid for gastric cancer patients has been investigated, especially for the detection of peritoneal dissemination and lymph node metastasis. This method enables intraoperative real-time fluorescence detection of peritoneal dissemination, exhibiting higher sensitivity than white light observation without histopathological examination. The method also enables detection of metastatic foci within excised lymph nodes, exhibiting a diagnostic accuracy comparable to that of a current molecular diagnostics technique. Although several complicating issues still need to be resolved, such as the effect of tissue autofluorescence and the insufficient depth penetration of excitation light, this simple and rapid method has the potential to become a useful diagnostic tool for gastric cancer, as well as urinary bladder cancer and glioma.", "classifications": [ { "id": "Tanaka", "label": "Group Tanaka", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Noriaki", "last_name": "Koizumi", "name": null }, { "creator_type": "author", "first_name": "Yoshinori", "last_name": "Harada", "name": null }, { "creator_type": "author", "first_name": "Takeo", "last_name": "Minamikawa", "name": null }, { "creator_type": "author", "first_name": "Hideo", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Eigo", "last_name": "Otsuji", "name": null }, { "creator_type": "author", "first_name": "Tetsuro", "last_name": "Takamatsu", "name": null } ], "identifiers": { "doi": { "normalized": "10.3748/wjg.v22.i3.1289" }, "pmcid": { "normalized": "PMC4716038" }, "pmid": { "normalized": "26811665" } }, "mesh": [ { "descriptor": "Aminolevulinic Acid", "descriptor_ui": "D000622", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Biomarkers, Tumor", "descriptor_ui": "D014408", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Intraoperative Care", "descriptor_ui": "D007430", "major_topic": false }, { "descriptor": "Luminescent Measurements", "descriptor_ui": "D008163", "major_topic": false }, { "descriptor": "Lymphatic Metastasis", "descriptor_ui": "D008207", "major_topic": false }, { "descriptor": "Molecular Diagnostic Techniques", "descriptor_ui": "D025202", "major_topic": true }, { "descriptor": "Peritoneal Neoplasms", "descriptor_ui": "D010534", "major_topic": false }, { "descriptor": "Predictive Value of Tests", "descriptor_ui": "D011237", "major_topic": false }, { "descriptor": "Protoporphyrins", "descriptor_ui": "D011524", "major_topic": false }, { "descriptor": "Reproducibility of Results", "descriptor_ui": "D015203", "major_topic": false }, { "descriptor": "Stomach Neoplasms", "descriptor_ui": "D013274", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016 Jan 21", "date_precision": "day", "issue": "3", "normalized_date": "2016-01-21", "pages": "1289-1296", "proceedings_title": null, "publisher": "", "title": "World journal of gastroenterology", "volume": "22", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Recent advances in photodynamic diagnosis of gastric cancer using 5-aminolevulinic acid.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The angiotensin (Ang) type 1 receptor (AT1R) promotes functional and structural integrity of the arterial wall to contribute to vascular homeostasis, but this receptor also promotes hypertension. In our investigation of how Ang II signals are converted by the AT1R from physiological to pathological outputs, we found that the purinergic P2Y6 receptor (P2Y6R), an inflammation-inducible G protein (heterotrimeric guanine nucleotide-binding protein)-coupled receptor (GPCR), promoted Ang II-induced hypertension in mice. In mice, deletion of P2Y6R attenuated Ang II-induced increase in blood pressure, vascular remodeling, oxidative stress, and endothelial dysfunction. AT1R and P2Y6R formed stable heterodimers, which enhanced G protein-dependent vascular hypertrophy but reduced beta-arrestin-dependent AT1R internalization. Pharmacological disruption of AT1R-P2Y6R heterodimers by the P2Y6R antagonist MRS2578 suppressed Ang II-induced hypertension in mice. Furthermore, P2Y6R abundance increased with age in vascular smooth muscle cells. The increased abundance of P2Y6R converted AT1R-stimulated signaling in vascular smooth muscle cells from beta-arrestin-dependent proliferation to G protein-dependent hypertrophy. These results suggest that increased formation of AT1R-P2Y6R heterodimers with age may increase the likelihood of hypertension induced by Ang II.", "classifications": [ { "id": "Nishida", "label": "Group Nishida", "parent": "Nishida", "type": "group" }, { "id": "Nishimura", "label": "Group Nishimura", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Akiyuki", "last_name": "Nishimura", "name": null }, { "creator_type": "author", "first_name": "Caroline", "last_name": "Sunggip", "name": null }, { "creator_type": "author", "first_name": "Hidetoshi", "last_name": "Tozaki-Saitoh", "name": null }, { "creator_type": "author", "first_name": "Tsukasa", "last_name": "Shimauchi", "name": null }, { "creator_type": "author", "first_name": "Takuro", "last_name": "Numaga-Tomita", "name": null }, { "creator_type": "author", "first_name": "Katsuya", "last_name": "Hirano", "name": null }, { "creator_type": "author", "first_name": "Tomomi", "last_name": "Ide", "name": null }, { "creator_type": "author", "first_name": "Jean-Marie", "last_name": "Boeynaems", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Kurose", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Tsuda", "name": null }, { "creator_type": "author", "first_name": "Bernard", "last_name": "Robaye", "name": null }, { "creator_type": "author", "first_name": "Kazuhide", "last_name": "Inoue", "name": null }, { "creator_type": "author", "first_name": "Motohiro", "last_name": "Nishida", "name": null } ], "identifiers": { "doi": { "normalized": "10.1126/scisignal.aac9187" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "26787451" } }, "mesh": [ { "descriptor": "Aging", "descriptor_ui": "D000375", "major_topic": false }, { "descriptor": "Angiotensin II", "descriptor_ui": "D000804", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "HEK293 Cells", "descriptor_ui": "D057809", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Hypertension", "descriptor_ui": "D006973", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Protein Multimerization", "descriptor_ui": "D055503", "major_topic": false }, { "descriptor": "Receptor, Angiotensin, Type 1", "descriptor_ui": "D044140", "major_topic": false }, { "descriptor": "Receptors, Purinergic P2", "descriptor_ui": "D018048", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016 Jan 19", "date_precision": "day", "issue": "411", "normalized_date": "2016-01-19", "pages": "ra7", "proceedings_title": null, "publisher": "", "title": "Science signaling", "volume": "9", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Purinergic P2Y6 receptors heterodimerize with angiotensin AT1 receptors to promote angiotensin II-induced hypertension.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Sustained activation of extracellular-signal-regulated kinase (ERK) has an important role in the decision regarding the cell fate of B-lymphocytes. Recently, we demonstrated that the diacylglycerol-activated non-selective cation channel canonical transient receptor potential 3 (TRPC3) is required for the sustained ERK activation induced by the B-cell receptor. However, the signalling mechanism underlying TRPC3-mediated ERK activation remains elusive. In the present study, we have shown that TRPC3 mediates Ca(2+) influx to sustain activation of protein kinase D (PKD) in a protein kinase C-dependent manner in DT40 B-lymphocytes. The later phase of ERK activation depends on the small G-protein Rap1, known as a downstream target of PKD, whereas the earlier phase of ERK activation depends on the Ras protein. It is of interest that sustained ERK phosphorylation is required for the full induction of the immediate early gene Egr-1 (early growth response 1). These results suggest that TRPC3 reorganizes the BCR signalling complex by switching the subtype of small G-proteins to sustain ERK activation in B-lymphocytes.", "classifications": [ { "id": "Nishida", "label": "Group Nishida", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Takuro", "last_name": "Numaga-Tomita", "name": null }, { "creator_type": "author", "first_name": "Motohiro", "last_name": "Nishida", "name": null }, { "creator_type": "author", "first_name": "James W. Jr", "last_name": "Putney", "name": null }, { "creator_type": "author", "first_name": "Yasuo", "last_name": "Mori", "name": null } ], "identifiers": { "doi": { "normalized": "10.1042/bj20150596" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "26554024" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "B-Lymphocytes", "descriptor_ui": "D001402", "major_topic": false }, { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "Chickens", "descriptor_ui": "D002645", "major_topic": false }, { "descriptor": "MAP Kinase Signaling System", "descriptor_ui": "D020935", "major_topic": false }, { "descriptor": "Protein Kinase C", "descriptor_ui": "D011493", "major_topic": false }, { "descriptor": "rap1 GTP-Binding Proteins", "descriptor_ui": "D020827", "major_topic": false }, { "descriptor": "TRPC Cation Channels", "descriptor_ui": "D050052", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016 Jan 15", "date_precision": "day", "issue": "2", "normalized_date": "2016-01-15", "pages": "201-210", "proceedings_title": null, "publisher": "", "title": "The Biochemical journal", "volume": "473", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "TRPC3 amplifies B-cell receptor-induced ERK signalling via protein kinase D-dependent Rap1 activation.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Cytoplasmic stress granules (SGs) are multimolecular aggregates of stalled translation pre-initiation complexes that prevent the accumulation of misfolded proteins, and that are formed in response to certain types of stress including ER stress. SG formation contributes to cell survival not only by suppressing translation but also by sequestering some apoptosis regulatory factors. Because cells can be exposed to various stresses simultaneously in vivo, the regulation of SG assembly under multiple stress conditions is important but unknown. Here we report that reactive oxygen species (ROS) such as H2O2 oxidize the SG-nucleating protein TIA1, thereby inhibiting SG assembly. Thus, when cells are confronted with a SG-inducing stress such as ER stress caused by protein misfolding, together with ROS-induced oxidative stress, they cannot form SGs, resulting in the promotion of apoptosis. We demonstrate that the suppression of SG formation by oxidative stress may underlie the neuronal cell death seen in neurodegenerative diseases.", "classifications": [ { "id": "Takekawa", "label": "Group Takekawa", "parent": "Takekawa", "type": "group" }, { "id": "Takekawa", "label": "Team Takekawa", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Kyoko", "last_name": "Arimoto-Matsuzaki", "name": null }, { "creator_type": "author", "first_name": "Haruo", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Mutsuhiro", "last_name": "Takekawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/ncomms10252" }, "pmcid": { "normalized": "PMC4729832" }, "pmid": { "normalized": "26738979" } }, "mesh": [ { "descriptor": "Apoptosis", "descriptor_ui": "D017209", "major_topic": false }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Cytoplasmic Granules", "descriptor_ui": "D003594", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Hydrogen Peroxide", "descriptor_ui": "D006861", "major_topic": false }, { "descriptor": "Oxidation-Reduction", "descriptor_ui": "D010084", "major_topic": false }, { "descriptor": "Poly(A)-Binding Proteins", "descriptor_ui": "D039102", "major_topic": false }, { "descriptor": "RNA-Binding Proteins", "descriptor_ui": "D016601", "major_topic": false }, { "descriptor": "Stress, Physiological", "descriptor_ui": "D013312", "major_topic": false }, { "descriptor": "T-Cell Intracellular Antigen-1", "descriptor_ui": "D000074019", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016 Jan 7", "date_precision": "day", "issue": "", "normalized_date": "2016-01-07", "pages": "10252", "proceedings_title": null, "publisher": "", "title": "Nature communications", "volume": "7", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "TIA1 oxidation inhibits stress granule assembly and sensitizes cells to stress-induced apoptosis.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Deep-UV (DUV) light is a sensitive probe for biological molecules such as nucleobases and aromatic amino acids due to specific absorption. However, the use of DUV light for imaging is limited because DUV can destroy or denature target molecules in a sample. Here we show that trivalent ions in the lanthanide group can suppress molecular photodegradation under DUV exposure, enabling a high signal-to-noise ratio and repetitive DUV imaging of nucleobases in cells. Underlying mechanisms of the photodegradation suppression can be excitation relaxation of the DUV-absorptive molecules due to energy transfer to the lanthanide ions, and/or avoiding ionization and reactions with surrounding molecules, including generation of reactive oxygen species, which can modify molecules that are otherwise transparent to DUV light. This approach, directly removing excited energy at the fundamental origin of cellular photodegradation, indicates an important first step towards the practical use of DUV imaging in a variety of biological applications.", "classifications": [ { "id": "Fujita", "label": "Group Fujita", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yasuaki", "last_name": "Kumamoto", "name": null }, { "creator_type": "author", "first_name": "Katsumasa", "last_name": "Fujita", "name": null }, { "creator_type": "author", "first_name": "Nicholas Isaac", "last_name": "Smith", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Kawata", "name": null } ], "identifiers": { "doi": { "normalized": "10.1364/boe.7.000158" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "26819825" } }, "mesh": [], "publication": { "conference_name": null, "date": "2016 Jan 01", "date_precision": "day", "issue": "1", "normalized_date": "2016-01-01", "pages": "158-170", "proceedings_title": null, "publisher": "", "title": "Biomedical Optics Express", "volume": "7", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Deep-UV biological imaging by lanthanide ion molecular protection.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The establishment of cancer stem-like cell (CSC) culture systems may be instrumental in devising strategies to fight refractory cancers. Inhibition of the Rho kinase ROCK has been shown to favorably affect CSC spheroid cultures. In this study, we show how ROCK inhibition in human serous ovarian cancer (SOC) cells can help establish a CSC system, which illuminates cancer pathophysiology and its treatment in this setting. In the presence of a ROCK kinase inhibitor, spheroid cultures of SOC cells expressed characteristic CSC markers including ALDH1A1, CD133, and SOX2, along with differentiation and tumorigenic capabilities in mouse xenograft models of human SOC. High expression levels of ALDH, but not CD133, correlated with spheroid formation CSC marker expression and tumor forming capability. In clinical specimens of SOC, high levels of ALDH1A1 correlated with advanced stage and poor prognosis. Pharmacologic or genetic blockade of ALDH blocked cell proliferation and reduced expression of SOX2, the genetic ablation of which abolished spheroid formation, whereas SOX2 overexpression inhibited ALDH1A1 expression and blocked spheroid proliferation. Taken together, our findings illustrated a new method to culture human ovarian CSC, and they defined a reciprocal regulatory relationship between ALDH1A1 and SOX2, which impacts ovarian CSC proliferation and malignant progression.", "classifications": [ { "id": "Okamoto", "label": "Group Okamoto", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Ishiguro", "name": null }, { "creator_type": "author", "first_name": "Ai", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Hirokazu", "last_name": "Ohata", "name": null }, { "creator_type": "author", "first_name": "Yoshinori", "last_name": "Ikarashi", "name": null }, { "creator_type": "author", "first_name": "Ryou-U.", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Takahiro", "last_name": "Ochiya", "name": null }, { "creator_type": "author", "first_name": "Masayuki", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Tsuda", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Onda", "name": null }, { "creator_type": "author", "first_name": "Tomoyasu", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Takahiro", "last_name": "Kasamatsu", "name": null }, { "creator_type": "author", "first_name": "Takayuki", "last_name": "Enomoto", "name": null }, { "creator_type": "author", "first_name": "Kenichi", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Nakagama", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Okamoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1158/0008-5472.can-15-0361" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "26669863" } }, "mesh": [ { "descriptor": "Carcinoma, Ovarian Epithelial", "descriptor_ui": "D000077216", "major_topic": false }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Cell Proliferation", "descriptor_ui": "D049109", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Immunohistochemistry", "descriptor_ui": "D007150", "major_topic": false }, { "descriptor": "Neoplasms, Glandular and Epithelial", "descriptor_ui": "D009375", "major_topic": false }, { "descriptor": "Neoplastic Stem Cells", "descriptor_ui": "D014411", "major_topic": false }, { "descriptor": "Ovarian Neoplasms", "descriptor_ui": "D010051", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016 Jan 1", "date_precision": "day", "issue": "1", "normalized_date": "2016-01-01", "pages": "150-160", "proceedings_title": null, "publisher": "", "title": "Cancer research", "volume": "76", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Establishment and Characterization of an In Vitro Model of Ovarian Cancer Stem-like Cells with an Enhanced Proliferative Capacity.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Ras protein is involved in a signal transduction cascade in cell growth, and cluster formation of H-Ras and human galectin-1 (Gal-1) complex is considered to be crucial to achieve its physiological roles. It is considered that the complex is formed through interactions between Gal-1 and the farnesyl group (farnesyl-dependent model), post-translationally modified to the C-terminal Cys, of H-Ras. We investigated the role of farnesyl-bound Gal-1 in the cluster formation by analyzing the structure and properties of Gal-1 bound to farnesyl thiosalicylic acid (FTS), a competitive inhibitor of the binding of H-Ras to Gal-1. Gal-1 exhibited self-cluster formation upon interaction with FTS, and small- and large-size clusters were formed depending on FTS concentration. The galactoside-binding pocket of Gal-1 in the FTS-bound form was found to play an important role in small-size cluster formation. Large-size clusters were likely formed by the interaction among the hydrophobic sites of Gal-1 in the FTS-bound form. The present results indicate that Gal-1 in the FTS-bound form has the ability to form self-clusters as well as intrinsic lectin activity. Relevance of the self-clustering of FTS-bound Gal-1 to the cluster formation of the H-Ras–Gal-1complex was discussed by taking account of the farnesyl-dependent model and another (Raf-dependent) model.", "classifications": [ { "id": "Nakabayashi", "label": "Group Nakabayashi", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Kazumi", "last_name": "Yamaguchi", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Niwa", "name": null }, { "creator_type": "author", "first_name": "Takakazu", "last_name": "Nakabayashi", "name": null }, { "creator_type": "author", "first_name": "Hirotsugu", "last_name": "Hiramatsu", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/srep32999" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "27624845" } }, "mesh": [ { "descriptor": "Binding Sites", "descriptor_ui": "D001665", "major_topic": false }, { "descriptor": "Farnesol", "descriptor_ui": "D005204", "major_topic": false }, { "descriptor": "Galectin 1", "descriptor_ui": "D037483", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Hydrophobic and Hydrophilic Interactions", "descriptor_ui": "D057927", "major_topic": false }, { "descriptor": "Models, Molecular", "descriptor_ui": "D008958", "major_topic": false }, { "descriptor": "Molecular Dynamics Simulation", "descriptor_ui": "D056004", "major_topic": false }, { "descriptor": "Protein Binding", "descriptor_ui": "D011485", "major_topic": false }, { "descriptor": "Protein Conformation", "descriptor_ui": "D011487", "major_topic": false }, { "descriptor": "Protein Processing, Post-Translational", "descriptor_ui": "D011499", "major_topic": false }, { "descriptor": "Proto-Oncogene Proteins p21(ras)", "descriptor_ui": "D016283", "major_topic": false }, { "descriptor": "Salicylates", "descriptor_ui": "D012459", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016", "date_precision": "year", "issue": "", "normalized_date": "2016", "pages": "", "proceedings_title": null, "publisher": "", "title": "Scientific Reports", "volume": "6", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Generation of self-clusters of galectin-1 in the farnesyl-bound form.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The genus Physalis in the Solanaceae family contains several species of benefit to humans. Examples include P. alkekengi (Chinese-lantern plant, hôzuki in Japanese) used for medicinal and for decorative purposes, and P. peruviana, also known as Cape gooseberry, which bears an edible, vitamin-rich fruit. Members of the Physalis genus are a valuable resource for phytochemicals needed for the development of medicines and functional foods. To fully utilize the potential of these phytochemicals we need to understand their biosynthesis, and for this we need genomic data, especially comprehensive transcriptome datasets for gene discovery. We report the de novo assembly of the transcriptome from leaves of P. alkekengi and P. peruviana using Illumina RNA-seq technologies. We identified 75,221 unigenes in P. alkekengi and 54,513 in P. peruviana. All unigenes were annotated with gene ontology (GO), Enzyme Commission (EC) numbers, and pathway information from the Kyoto Encyclopedia of Genes and Genomes (KEGG). We classified unigenes encoding enzyme candidates putatively involved in the secondary metabolism and identified more than one unigenes for each step in terpenoid backbone- and steroid biosynthesis in P. alkekengi and P. peruviana. To measure the variability of the withanolides including physalins and provide insights into their chemical diversity in Physalis, we also analyzed the metabolite content in leaves of P. alkekengi and P. peruviana at five different developmental stages by liquid chromatography-mass spectrometry. We discuss that comprehensive transcriptome approaches within a family can yield a clue for gene discovery in Physalis and provide insights into their complex chemical diversity. The transcriptome information we submit here will serve as an important public resource for further studies of the specialized metabolism of Physalis species.", "classifications": [ { "id": "Sodeoka", "label": "Group Sodeoka", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Atsushi", "last_name": "Fukushima", "name": null }, { "creator_type": "author", "first_name": "Michimi", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Hideyuki", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Mami", "last_name": "Yamazaki", "name": null }, { "creator_type": "author", "first_name": "Eva", "last_name": "Knoch", "name": null }, { "creator_type": "author", "first_name": "Tetsuya", "last_name": "Mori", "name": null }, { "creator_type": "author", "first_name": "Naoyuki", "last_name": "Umemoto", "name": null }, { "creator_type": "author", "first_name": "Masaki", "last_name": "Morita", "name": null }, { "creator_type": "author", "first_name": "Go", "last_name": "Hirai", "name": null }, { "creator_type": "author", "first_name": "Mikiko", "last_name": "Sodeoka", "name": null }, { "creator_type": "author", "first_name": "Kazuki", "last_name": "Saito", "name": null } ], "identifiers": { "doi": { "normalized": "10.3389/fpls.2016.01883" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "28066454" } }, "mesh": [], "publication": { "conference_name": null, "date": "2016", "date_precision": "year", "issue": "", "normalized_date": "2016", "pages": "", "proceedings_title": null, "publisher": "", "title": "Frontiers in Plant Science", "volume": "7", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Comparative Characterization of the Leaf Tissue of Physalis alkekengi and Physalis peruviana Using RNA-seq and Metabolite Profiling.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "", "classifications": [ { "id": "Okamoto", "label": "Group Okamoto", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Daniel J.", "last_name": "Klionsky", "name": null }, { "creator_type": "author", "first_name": "Kotb", "last_name": "Abdelmohsen", "name": null }, { "creator_type": "author", "first_name": "Akihisa", "last_name": "Abe", "name": null }, { "creator_type": "author", "first_name": "Md Joynal", "last_name": "Abedin", "name": null }, { "creator_type": "author", "first_name": "Hagai", "last_name": "Abeliovich", "name": null }, { "creator_type": "author", "first_name": "Abraham", "last_name": "Acevedo Arozena", "name": null }, { "creator_type": "author", "first_name": "Hiroaki", "last_name": "Adachi", "name": null }, { "creator_type": "author", "first_name": "Christopher M.", "last_name": "Adams", "name": null }, { "creator_type": "author", "first_name": "Peter D.", "last_name": "Adams", "name": null }, { "creator_type": "author", "first_name": "Khosrow", "last_name": "Adeli", "name": null }, { "creator_type": "author", "first_name": "Peter J.", "last_name": "Adhihetty", "name": null }, { "creator_type": "author", "first_name": "Sharon G.", "last_name": "Adler", "name": null }, { "creator_type": "author", "first_name": "Galila", "last_name": "Agam", "name": null }, { "creator_type": "author", "first_name": "Rajesh", "last_name": "Agarwal", "name": null }, { "creator_type": "author", "first_name": "Manish K.", "last_name": "Aghi", "name": null }, { "creator_type": "author", "first_name": "Maria", "last_name": "Agnello", "name": null }, { "creator_type": "author", "first_name": "Patrizia", "last_name": "Agostinis", "name": null }, { "creator_type": "author", "first_name": "Patricia V.", "last_name": "Aguilar", "name": null }, { "creator_type": "author", "first_name": "Julio", "last_name": "Aguirre-Ghiso", "name": null }, { "creator_type": "author", "first_name": "Edoardo M.", "last_name": "Airoldi", "name": null }, { "creator_type": "author", "first_name": "Slimane", "last_name": "Ait-Si-Ali", "name": null }, { "creator_type": "author", "first_name": "Takahiko", "last_name": "Akematsu", "name": null }, { "creator_type": "author", "first_name": "Emmanuel T.", "last_name": "Akporiaye", "name": null }, { "creator_type": "author", "first_name": "Mohamed", "last_name": "Al-Rubeai", "name": null }, { "creator_type": "author", "first_name": "Guillermo M.", "last_name": "Albaiceta", "name": null }, { "creator_type": "author", "first_name": "Chris", "last_name": "Albanese", "name": null }, { "creator_type": "author", "first_name": "Diego", "last_name": "Albani", "name": null }, { "creator_type": "author", "first_name": "Matthew L.", "last_name": "Albert", "name": null }, { "creator_type": "author", "first_name": "Jesus", "last_name": "Aldudo", "name": null }, { "creator_type": "author", "first_name": 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}, { "creator_type": "author", "first_name": "Qing", "last_name": "Zhong", "name": null }, { "creator_type": "author", "first_name": "Guang-Zhou", "last_name": "Zhou", "name": null }, { "creator_type": "author", "first_name": "Guofei", "last_name": "Zhou", "name": null }, { "creator_type": "author", "first_name": "Huiping", "last_name": "Zhou", "name": null }, { "creator_type": "author", "first_name": "Shu-Feng", "last_name": "Zhou", "name": null }, { "creator_type": "author", "first_name": "Xu-Jie", "last_name": "Zhou", "name": null }, { "creator_type": "author", "first_name": "Hongxin", "last_name": "Zhu", "name": null }, { "creator_type": "author", "first_name": "Hua", "last_name": "Zhu", "name": null }, { "creator_type": "author", "first_name": "Wei-Guo", "last_name": "Zhu", "name": null }, { "creator_type": "author", "first_name": "Wenhua", "last_name": "Zhu", "name": null }, { "creator_type": "author", "first_name": "Xiao-Feng", "last_name": "Zhu", "name": null }, { "creator_type": "author", "first_name": "Yuhua", "last_name": "Zhu", "name": null }, { "creator_type": "author", "first_name": "Shi-Mei", "last_name": "Zhuang", "name": null }, { "creator_type": "author", "first_name": "Xiaohong", "last_name": "Zhuang", "name": null }, { "creator_type": "author", "first_name": "Elio", "last_name": "Ziparo", "name": null }, { "creator_type": "author", "first_name": "Christos E.", "last_name": "Zois", "name": null }, { "creator_type": "author", "first_name": "Teresa", "last_name": "Zoladek", "name": null }, { "creator_type": "author", "first_name": "Wei-Xing", "last_name": "Zong", "name": null }, { "creator_type": "author", "first_name": "Antonio", "last_name": "Zorzano", "name": null }, { "creator_type": "author", "first_name": "Susu M.", "last_name": "Zughaier", "name": null } ], "identifiers": { "doi": { "normalized": "10.1080/15548627.2015.1100356" }, "pmcid": { "normalized": "PMC4835977" }, "pmid": { "normalized": "26799652" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Autophagy", "descriptor_ui": "D001343", "major_topic": true }, { "descriptor": "Biological Assay", "descriptor_ui": "D001681", "major_topic": false }, { "descriptor": "Computer Simulation", "descriptor_ui": "D003198", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016", "date_precision": "year", "issue": "1", "normalized_date": "2016", "pages": "1-222", "proceedings_title": null, "publisher": "", "title": "Autophagy", "volume": "12", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition).", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Neurons and glia in the central nervous system (CNS) originate from neural stem cells (NSCs). Knowledge of the mechanisms of neuro/gliogenesis from NSCs is fundamental to our understanding of how complex brain architecture and function develop. NSCs are present not only in the developing brain but also in the mature brain in adults. Adult neurogenesis likely provides remarkable plasticity to the mature brain. In addition, recent progress in basic research in mental disorders suggests an etiological link with impaired neuro/gliogenesis in particular brain regions. Here, we review the recent progress and discuss future directions in stem cell and neuro/gliogenesis biology by introducing several topics presented at a joint meeting of the Japanese Association of Anatomists and the Physiological Society of Japan in 2015. Collectively, these topics indicated that neuro/gliogenesis from NSCs is a common event occurring in many brain regions at various ages in animals. Given that significant structural and functional changes in cells and neural networks are accompanied by neuro/gliogenesis from NSCs and the integration of newly generated cells into the network, stem cell and neuro/gliogenesis biology provides a good platform from which to develop an integrated understanding of the structural and functional plasticity that underlies the development of the CNS, its remodeling in adulthood, and the recovery from diseases that affect it.", "classifications": [ { "id": "Imayoshi", "label": "Group Imayoshi", "parent": "Imayoshi", "type": "group" }, { "id": "Imayoshi", "label": "Team Imayoshi", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Masahiro", "last_name": "Yamaguchi", "name": null }, { "creator_type": "author", "first_name": "Tatsunori", "last_name": "Seki", "name": null }, { "creator_type": "author", "first_name": "Itaru", "last_name": "Imayoshi", "name": null }, { "creator_type": "author", "first_name": "Nobuaki", "last_name": "Tamamaki", "name": null }, { "creator_type": "author", "first_name": "Yoshitaka", "last_name": "Hayashi", "name": null }, { "creator_type": "author", "first_name": "Yoshitaka", "last_name": "Tatebayashi", "name": null }, { "creator_type": "author", "first_name": "Seiji", "last_name": "Hitoshi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/s12576-015-0421-4" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "26578509" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Brain", "descriptor_ui": "D001921", "major_topic": false }, { "descriptor": "Central Nervous System", "descriptor_ui": "D002490", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Neural Stem Cells", "descriptor_ui": "D058953", "major_topic": false }, { "descriptor": "Neurogenesis", "descriptor_ui": "D055495", "major_topic": false }, { "descriptor": "Neuroglia", "descriptor_ui": "D009457", "major_topic": false }, { "descriptor": "Neuronal Plasticity", "descriptor_ui": "D009473", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016", "date_precision": "year", "issue": "", "normalized_date": "2016", "pages": "197-206", "proceedings_title": null, "publisher": "", "title": "The Journal of Physiological Sciences", "volume": "66", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Neural stem cells and neuro/gliogenesis in the central nervous system: understanding the structural and functional plasticity of the developing, mature, and diseased brain.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "OBJECTIVE: Physical activity is known to be preventive against various non-communicable diseases. We investigated the relationship between daily physical activity level and plasma metabolites using a targeted metabolomics approach in a population-based study. METHODS: A total of 1,193 participants (male, aged 35 to 74 years) with fasting blood samples were selected from the baseline survey of a cohort study. Information on daily total physical activity, classified into four levels by quartile of metabolic equivalent scores, and sedentary behavior, defined as hours of sitting per day, was collected through a self-administered questionnaire. Plasma metabolite concentrations were quantified by capillary electrophoresis mass spectrometry method. We performed linear regression analysis models with multivariable adjustment and corrected p-values for multiple testing in the original population (n = 808). The robustness of the results was confirmed by replication analysis in a separate population (n = 385) created by random allocation. RESULTS: Higher levels of total physical activity were associated with various metabolite concentrations, including lower concentrations of amino acids and their derivatives, and higher concentrations of pipecolate (FDR p <0.05 in original population). The findings persisted after adjustment for age, body mass index, smoking, alcohol intake, and energy intake. Isoleucine, leucine, valine, 4-methyl-2-oxoisopentanoate, 2-oxoisopentanoate, alanine, and proline concentrations were lower with a shorter sitting time. CONCLUSIONS: Physical activity is related to various plasma metabolites, including known biomarkers for future insulin resistance or type 2 diabetes. These metabolites might potentially play a key role in the protective effects of higher physical activity and/or less sedentary behavior on non-communicable diseases.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Kota", "last_name": "Fukai", "name": null }, { "creator_type": "author", "first_name": "Sei", "last_name": "Harada", "name": null }, { "creator_type": "author", "first_name": "Miho", "last_name": "Iida", "name": null }, { "creator_type": "author", "first_name": "Ayako", "last_name": "Kurihara", "name": null }, { "creator_type": "author", "first_name": "Ayano", "last_name": "Takeuchi", "name": null }, { "creator_type": "author", "first_name": "Kazuyo", "last_name": "Kuwabara", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Sugiyama", "name": null }, { "creator_type": "author", "first_name": "Tomonori", "last_name": "Okamura", "name": null }, { "creator_type": "author", "first_name": "Miki", "last_name": "Akiyama", "name": null }, { "creator_type": "author", "first_name": "Yuji", "last_name": "Nishiwaki", "name": null }, { "creator_type": "author", "first_name": "Yuko", "last_name": "Oguma", "name": null }, { "creator_type": "author", "first_name": "Asako", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Chizuru", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Akiyoshi", "last_name": "Hirayama", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Sugimoto", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Masaru", "last_name": "Tomita", "name": null }, { "creator_type": "author", "first_name": "Toru", "last_name": "Takebayashi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1371/journal.pone.0164877" }, "pmcid": { "normalized": "PMC5065216" }, "pmid": { "normalized": "27741291" } }, "mesh": [ { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Amino Acids", "descriptor_ui": "D000596", "major_topic": false }, { "descriptor": "Biomarkers", "descriptor_ui": "D015415", "major_topic": false }, { "descriptor": "Electrophoresis, Capillary", "descriptor_ui": "D019075", "major_topic": false }, { "descriptor": "Hemiterpenes", "descriptor_ui": "D045782", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Keto Acids", "descriptor_ui": "D007651", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mass Spectrometry", "descriptor_ui": "D013058", "major_topic": false }, { "descriptor": "Metabolomics", "descriptor_ui": "D055432", "major_topic": true }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Motor Activity", "descriptor_ui": "D009043", "major_topic": false }, { "descriptor": "Sedentary Behavior", "descriptor_ui": "D057185", "major_topic": true }, { "descriptor": "Self Report", "descriptor_ui": "D057566", "major_topic": false }, { "descriptor": "Surveys and Questionnaires", "descriptor_ui": "D011795", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016", "date_precision": "year", "issue": "10", "normalized_date": "2016", "pages": "e0164877", "proceedings_title": null, "publisher": "", "title": "PloS one", "volume": "11", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Metabolic Profiling of Total Physical Activity and Sedentary Behavior in Community-Dwelling Men.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Modification of our previously reported selective inhibitor of oxidative stress-induced necrosis, 2-(1H-indol-3-yl)-3-pentylamino-maleimide (IM-54) by regioselective reduction of the C-4 carbonyl group afforded a 3-amino-2-indolyllactam (IL-1) with more potent activity. To examine the structure-activity relationship of IL derivatives, we developed new synthetic routes with flexibility to incorporate a range of substituents at a late stage. The synthesized IL derivatives were evaluated for activity to inhibit necrotic cell death induced by hydrogen peroxide. Among them, IL-12 showed the most potent activity (IC50=49 nM) among the IL and indolylmaleimide (IM) derivatives examined.", "classifications": [ { "id": "Sodeoka", "label": "Group Sodeoka", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Kosuke", "last_name": "Dodo", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Hayamizu", "name": null }, { "creator_type": "author", "first_name": "Tadashi", "last_name": "Shimizu", "name": null }, { "creator_type": "author", "first_name": "Mikiko", "last_name": "Sodeoka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1248/cpb.c16-00259" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "27373644" } }, "mesh": [ { "descriptor": "Cell Death", "descriptor_ui": "D016923", "major_topic": false }, { "descriptor": "Dose-Response Relationship, Drug", "descriptor_ui": "D004305", "major_topic": false }, { "descriptor": "HL-60 Cells", "descriptor_ui": "D018922", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Hydrogen Peroxide", "descriptor_ui": "D006861", "major_topic": false }, { "descriptor": "Indoles", "descriptor_ui": "D007211", "major_topic": false }, { "descriptor": "Lactams", "descriptor_ui": "D007769", "major_topic": false }, { "descriptor": "Molecular Structure", "descriptor_ui": "D015394", "major_topic": false }, { "descriptor": "Necrosis", "descriptor_ui": "D009336", "major_topic": false }, { "descriptor": "Oxidative Stress", "descriptor_ui": "D018384", "major_topic": false }, { "descriptor": "Structure-Activity Relationship", "descriptor_ui": "D013329", "major_topic": false }, { "descriptor": "Tumor Cells, Cultured", "descriptor_ui": "D014407", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016", "date_precision": "year", "issue": "7", "normalized_date": "2016", "pages": "886-898", "proceedings_title": null, "publisher": "", "title": "Chemical & pharmaceutical bulletin", "volume": "64", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Structure-Activity Relationship Study of 3-Amino-2-indolyllactam Derivatives: Development of Inhibitors of Oxidative Stress-Induced Necrosis.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Sialic acid bound to glycans in glycolipids and glycoproteins is essential for synaptic plasticity and memory. Sialidase (EC 3.2.1.18), which has 4 isozymes including Neu1, Neu2, Neu3 and Neu4, regulates the sialylation level of glycans by removing sialic acid from sialylglycoconjugate. In the present study, we investigated the distribution of sialidase activity in rat hippocampus and the role of sialidase in hippocampal memory processing. We previously developed a highly sensitive histochemical imaging probe for sialidase activity, BTP3-Neu5Ac. BTP3-Neu5Ac was cleaved efficiently by rat Neu2 and Neu4 at pH 7.3 and by Neu1 and Neu3 at pH 4.6. When a rat hippocampal acute slice was stained with BTP3-Neu5Ac at pH 7.3, mossy fiber terminal fields showed relatively intense sialidase activity. Thus, the role of sialidase in the synaptic plasticity was investigated at mossy fiber terminal fields. The long-term potentiation (LTP) at mossy fiber-CA3 pyramidal cell synapses was impaired by 2,3-dehydro-2-deoxy-N-acetylneuraminic acid (DANA), a sialidase inhibitor. DANA also failed to decrease paired-pulse facilitation after LTP induction. We also investigated the role of sialidase in hippocampus-dependent spatial memory by using the Morris water maze. The escape latency time to reach the platform was prolonged by DANA injection into the hippocampal CA3 region or by knockdown of Neu4 without affecting motility. The results show that the regulation of sialyl signaling by Neu4 is involved in hippocampal memory processing.", "classifications": [ { "id": "Suzuki", "label": "Group Suzuki", "parent": "Takekawa", "type": "group" }, { "id": "Takekawa", "label": "Team Takekawa", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Akira", "last_name": "Minami", "name": null }, { "creator_type": "author", "first_name": "Masakazu", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Shou", "last_name": "Mamada", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Ieno", "name": null }, { "creator_type": "author", "first_name": "Tomoya", "last_name": "Hikita", "name": null }, { "creator_type": "author", "first_name": "Tadanobu", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Tadamune", "last_name": "Otsubo", "name": null }, { "creator_type": "author", "first_name": "Kiyoshi", "last_name": "Ikeda", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Suzuki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1371/journal.pone.0165257" }, "pmcid": { "normalized": "PMC5081204" }, "pmid": { "normalized": "27783694" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Hippocampus", "descriptor_ui": "D006624", "major_topic": false }, { "descriptor": "Isoenzymes", "descriptor_ui": "D007527", "major_topic": false }, { "descriptor": "Long-Term Potentiation", "descriptor_ui": "D017774", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Maze Learning", "descriptor_ui": "D018782", "major_topic": false }, { "descriptor": "N-Acetylneuraminic Acid", "descriptor_ui": "D019158", "major_topic": false }, { "descriptor": "Neuraminidase", "descriptor_ui": "D009439", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Rats, Wistar", "descriptor_ui": "D017208", "major_topic": false }, { "descriptor": "RNA Interference", "descriptor_ui": "D034622", "major_topic": false }, { "descriptor": "RNA, Small Interfering", "descriptor_ui": "D034741", "major_topic": false }, { "descriptor": "Spatial Memory", "descriptor_ui": "D065852", "major_topic": false }, { "descriptor": "Synapses", "descriptor_ui": "D013569", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016", "date_precision": "year", "issue": "10", "normalized_date": "2016", "pages": "e0165257", "proceedings_title": null, "publisher": "", "title": "PloS one", "volume": "11", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Role of Sialidase in Long-Term Potentiation at Mossy Fiber-CA3 Synapses and Hippocampus-Dependent Spatial Memory.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Background: Phlyctenular keratitis is a hypersensitivity reaction of the cornea, and a complication of eyelid margin disease in children and young adults. In this study, we compared the morphology of the meibomian glands in eyelids between phlyctenular keratitis patients and healthy young adults, using noncontact meibography. Methods: The study included 16 eyes of 13 patients diagnosed with phlyctenular keratitis and 17 eyes of 17 healthy volunteers. Slit-lamp observations of the cornea and eyelid were performed on all subjects. The morphology of the meibomian glands was scored using non-contact meibography (meiboscore). The meiboscore in worse eye was used in bilateral phlyctenular keratitis. Results: All eyes with phlyctenular keratitis, but not normal controls, showed corneal nodules, neovascularization, and superficial punctate keratopathy. The mean meiboscore in phlyctenular keratitis patients (upper lid: 2.9 ± 0.3, lower lid: 2.7 ± 0.5) was significantly higher than in controls (upper lid: 0.4 ± 0.6, lower lid: 0.1 ± 0.3). Conclusions: Noncontact meibography enabled visualization of meibomian gland loss in phlyctenular keratitis patients, suggesting a relationship between abnormalities of the meibomian glands in young individuals and the pathogenesis of phlyctenular keratitis. Electronic supplementary material: The online version of this article (doi:10.1186/s12886-016-0347-5) contains supplementary material, which is available to authorized users.", "classifications": [ { "id": "Suzuki", "label": "Group Suzuki", "parent": "Takekawa", "type": "group" }, { "id": "Takekawa", "label": "Team Takekawa", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Takashi", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Naoyuki", "last_name": "Morishige", "name": null }, { "creator_type": "author", "first_name": "Reiko", "last_name": "Arita", "name": null }, { "creator_type": "author", "first_name": "Shizuka", "last_name": "Koh", "name": null }, { "creator_type": "author", "first_name": "Tohru", "last_name": "Sakimoto", "name": null }, { "creator_type": "author", "first_name": "Rika", "last_name": "Shirakawa", "name": null }, { "creator_type": "author", "first_name": "Kazunori", "last_name": "Miyata", "name": null }, { "creator_type": "author", "first_name": "Yuichi", "last_name": "Ohashi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1186/s12886-016-0347-5" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "27724848" } }, "mesh": [ { "descriptor": "Adolescent", "descriptor_ui": "D000293", "major_topic": false }, { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Case-Control Studies", "descriptor_ui": "D016022", "major_topic": false }, { "descriptor": "Child", "descriptor_ui": "D002648", "major_topic": false }, { "descriptor": "Corneal Neovascularization", "descriptor_ui": "D016510", "major_topic": false }, { "descriptor": "Cross-Sectional Studies", "descriptor_ui": "D003430", "major_topic": false }, { "descriptor": "Eyelid Diseases", "descriptor_ui": "D005141", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Keratitis", "descriptor_ui": "D007634", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Meibomian Glands", "descriptor_ui": "D008537", "major_topic": false }, { "descriptor": "Young Adult", "descriptor_ui": "D055815", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016", "date_precision": "year", "issue": "", "normalized_date": "2016", "pages": "", "proceedings_title": null, "publisher": "", "title": "BMC Ophthalmology", "volume": "16", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Morphological changes in the meibomian glands of patients with phlyctenular keratitis: a multicenter cross-sectional study.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "", "classifications": [ { "id": "Hamamoto", "label": "Group Hamamoto", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Youping", "last_name": "Deng", "name": null }, { "creator_type": "author", "first_name": "Hongwei", "last_name": "Wang", "name": null }, { "creator_type": "author", "first_name": "Ryuji", "last_name": "Hamamoto", "name": null }, { "creator_type": "author", "first_name": "Shiwei", "last_name": "Duan", "name": null }, { "creator_type": "author", "first_name": "Mehdi", "last_name": "Pirooznia", "name": null }, { "creator_type": "author", "first_name": "Yongsheng", "last_name": "Bai", "name": null } ], "identifiers": { "doi": { "normalized": "10.1155/2016/2625831" }, "pmcid": { "normalized": "PMC5138440" }, "pmid": { "normalized": "27995138" } }, "mesh": [ { "descriptor": "Biomedical Research", "descriptor_ui": "D035843", "major_topic": true }, { "descriptor": "Computational Biology", "descriptor_ui": "D019295", "major_topic": true }, { "descriptor": "Disease", "descriptor_ui": "D004194", "major_topic": false }, { "descriptor": "Genomics", "descriptor_ui": "D023281", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016", "date_precision": "year", "issue": "", "normalized_date": "2016", "pages": "2625831", "proceedings_title": null, "publisher": "", "title": "BioMed research international", "volume": "2016", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Functional Genomics, Genetics, and Bioinformatics 2016.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "This study aimed to identify the computed tomography characteristics of treatment-naïve patients with lung adenocarcinoma and known driver mutations in EGFR, KRAS, or ALK. Patients with advanced lung adenocarcinoma (stage IIIB-IV) and known mutations in EGFR, KRAS, or ALK were assessed. The radiological findings for the main tumor and intra-thoracic status were retrospectively analyzed in each group, and the groups' characteristics were compared. We identified 265 treatment-naïve patients with non-small-cell carcinoma, who had EGFR mutations (n = 159), KRAS mutations (n = 55), or ALK rearrangements (n = 51). Among the three groups, we evaluated only patients with stage IIIB-IV lung adenocarcinoma who had EGFR mutations (n = 126), KRAS mutations (n = 35), or ALK rearrangements (n = 47). We found that ground-glass opacity at the main tumor was significantly more common among EGFR-positive patients, compared to ALK-positive patients (p = 0.009). Lymphadenopathy was significantly more common among ALK-positive patients, compared to EGFR-positive patients (p = 0.003). Extranodal invasion was significantly more common among ALK-positive patients, compared to EGFR-positive patients and KRAS-positive patients (p = 0.001 and p = 0.049, respectively). Lymphangitis was significantly more common among ALK-positive patients, compared to EGFR-positive patients (p = 0.049). Pleural effusion was significantly less common among KRAS-positive patients, compared to EGFR-positive patients and ALK-positive patients (p = 0.046 and p = 0.026, respectively). Lung metastases were significantly more common among EGFR-positive patients, compared to KRAS-positive patients and ALK-positive patients (p = 0.007 and p = 0.04, respectively). In conclusion, EGFR mutations were associated with ground-glass opacity, KRAS-positive tumors were generally solid and less likely to metastasize to the lung and pleura, and ALK-positive tumors tended to present with lymphadenopathy, extranodal invasion, and lymphangitis. These mutation-specific imaging characteristics may be related to the biological differences between these cancers.", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Jangchul", "last_name": "Park", "name": null }, { "creator_type": "author", "first_name": "Yoshihisa", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Kevin Y.", "last_name": "Urayama", "name": null }, { "creator_type": "author", "first_name": "Hidekazu", "last_name": "Yamaura", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null }, { "creator_type": "author", "first_name": "Toyoaki", "last_name": "Hida", "name": null } ], "identifiers": { "doi": { "normalized": "10.1371/journal.pone.0161081" }, "pmcid": { "normalized": "PMC4982673" }, "pmid": { "normalized": "27518729" } }, "mesh": [ { "descriptor": "Adenocarcinoma", "descriptor_ui": "D000230", "major_topic": false }, { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Aged, 80 and over", "descriptor_ui": "D000369", "major_topic": false }, { "descriptor": "Anaplastic Lymphoma Kinase", "descriptor_ui": "D000077548", "major_topic": false }, { "descriptor": "Carcinoma, Large Cell", "descriptor_ui": "D018287", "major_topic": false }, { "descriptor": "Carcinoma, Non-Small-Cell Lung", "descriptor_ui": "D002289", "major_topic": false }, { "descriptor": "Carcinoma, Squamous Cell", "descriptor_ui": "D002294", "major_topic": false }, { "descriptor": "ErbB Receptors", "descriptor_ui": "D066246", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Gene Rearrangement", "descriptor_ui": "D015321", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Image Processing, Computer-Assisted", "descriptor_ui": "D007091", "major_topic": false }, { "descriptor": "Lung Neoplasms", "descriptor_ui": "D008175", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": false }, { "descriptor": "Neoplasm Staging", "descriptor_ui": "D009367", "major_topic": false }, { "descriptor": "Prognosis", "descriptor_ui": "D011379", "major_topic": false }, { "descriptor": "Proto-Oncogene Proteins p21(ras)", "descriptor_ui": "D016283", "major_topic": false }, { "descriptor": "Receptor Protein-Tyrosine Kinases", "descriptor_ui": "D020794", "major_topic": false }, { "descriptor": "Retrospective Studies", "descriptor_ui": "D012189", "major_topic": false }, { "descriptor": "Tomography, X-Ray Computed", "descriptor_ui": "D014057", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016", "date_precision": "year", "issue": "8", "normalized_date": "2016", "pages": "e0161081", "proceedings_title": null, "publisher": "", "title": "PloS one", "volume": "11", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Imaging Characteristics of Driver Mutations in EGFR, KRAS, and ALK among Treatment-Naïve Patients with Advanced Lung Adenocarcinoma.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Modern biology has provided many examples of large networks describing the interactions between multiple species of bio-molecules. It is believed that the dynamics of molecular activities based on such networks are the origin of biological functions. On the other hand, we have a limited understanding for dynamics of molecular activity based on networks. To overcome this problem, we have developed two structural theories, by which the important aspects of the dynamical properties of the system are determined only from information on the network structure, without assuming other quantitative details. The first theory, named Linkage Logic, determines a subset of molecules in regulatory networks, by which any long-term dynamical behavior of the whole system can be identified/controlled. The second theory, named Structural Sensitivity Analysis, determines the sensitivity responses of the steady state of chemical reaction networks to perturbations of the reaction rate. The first and second theories investigate the dynamical properties of regulatory and reaction networks, respectively. The first theory targets the attractors of the regulatory network systems, whereas the second theory applies only to the steady states of the reaction network systems, but predicts their detailed behavior. To demonstrate the utility of our methods several biological network systems, and show they are practically useful to analyze behaviors of biological systems.", "classifications": [ { "id": "Mochizuki", "label": "Group Mochizuki", "parent": "Eiraku", "type": "group" }, { "id": "Eiraku", "label": "Team Eiraku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Atsushi", "last_name": "Mochizuki", "name": null } ], "identifiers": { "doi": { "normalized": "10.2183/pjab.92.255" }, "pmcid": { "normalized": "PMC5243945" }, "pmid": { "normalized": "27725468" } }, "mesh": [ { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Feedback", "descriptor_ui": "D005246", "major_topic": false }, { "descriptor": "Logic", "descriptor_ui": "D008128", "major_topic": false }, { "descriptor": "Metabolic Networks and Pathways", "descriptor_ui": "D053858", "major_topic": true }, { "descriptor": "Models, Theoretical", "descriptor_ui": "D008962", "major_topic": true }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016", "date_precision": "year", "issue": "8", "normalized_date": "2016", "pages": "255-264", "proceedings_title": null, "publisher": "", "title": "Proceedings of the Japan Academy. Series B, Physical and biological sciences", "volume": "92", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Theoretical approaches for the dynamics of complex biological systems from information of networks.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: Many human studies report that nitric oxide (NO) improves sport performance. This is because NO is a potential modulator of blood flow, muscle energy metabolism, and mitochondrial respiration during exercise. L-Citrulline is an amino acid present in the body and is a potent endogenous precursor of L-arginine, which is a substrate for NO synthase. Here, we investigated the effect of oral L-citrulline supplementation on cycling time trial performance in humans. METHODS: A double-blind randomized placebo-controlled 2-way crossover study was employed. Twenty-two trained males consumed 2.4 g/day of L-citrulline or placebo orally for 7 days. On Day 8 they took 2.4 g of L-citrulline or placebo 1 h before a 4-km cycling time trial. Time taken to complete the 4 km cycle, along with power output/VO2 ratio (PO/VO2), plasma nitrite and nitrate (NOx) and amino acid levels, and visual analog scale (VAS) scores, was evaluated. RESULTS: L-Citrulline supplementation significantly increased plasma L-arginine levels and reduced completion time by 1.5 % (p < 0.05) compared with placebo. Moreover, L-citrulline significantly improved subjective feelings of muscle fatigue and concentration immediately after exercise. CONCLUSIONS: Oral L-citrulline supplementation reduced the time take to complete a cycle ergometer exercise trial. TRIAL REGISTRATION: Current Controlled Trials UMIN000014278.", "classifications": [ { "id": "Suzuki", "label": "Group Suzuki", "parent": "Takekawa", "type": "group" }, { "id": "Takekawa", "label": "Team Takekawa", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Takashi", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Masahiko", "last_name": "Morita", "name": null }, { "creator_type": "author", "first_name": "Yoshinori", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Ayako", "last_name": "Kamimura", "name": null } ], "identifiers": { "doi": { "normalized": "10.1186/s12970-016-0117-z" }, "pmcid": { "normalized": "PMC4759860" }, "pmid": { "normalized": "26900386" } }, "mesh": [ { "descriptor": "Administration, Oral", "descriptor_ui": "D000284", "major_topic": false }, { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Asian People", "descriptor_ui": "D044466", "major_topic": true }, { "descriptor": "Bicycling", "descriptor_ui": "D001642", "major_topic": true }, { "descriptor": "Biomarkers", "descriptor_ui": "D015415", "major_topic": false }, { "descriptor": "Blood Pressure", "descriptor_ui": "D001794", "major_topic": false }, { "descriptor": "Citrulline", "descriptor_ui": "D002956", "major_topic": false }, { "descriptor": "Cross-Over Studies", "descriptor_ui": "D018592", "major_topic": false }, { "descriptor": "Dietary Supplements", "descriptor_ui": "D019587", "major_topic": true }, { "descriptor": "Double-Blind Method", "descriptor_ui": "D004311", "major_topic": false }, { "descriptor": "Exercise Tolerance", "descriptor_ui": "D017079", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Muscle, Skeletal", "descriptor_ui": "D018482", "major_topic": false }, { "descriptor": "Nitric Oxide Synthase", "descriptor_ui": "D019001", "major_topic": false }, { "descriptor": "Oxygen Consumption", "descriptor_ui": "D010101", "major_topic": false }, { "descriptor": "Performance-Enhancing Substances", "descriptor_ui": "D058573", "major_topic": false }, { "descriptor": "Sports Nutritional Physiological Phenomena", "descriptor_ui": "D064133", "major_topic": false }, { "descriptor": "Treatment Outcome", "descriptor_ui": "D016896", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016", "date_precision": "year", "issue": "", "normalized_date": "2016", "pages": "6", "proceedings_title": null, "publisher": "", "title": "Journal of the International Society of Sports Nutrition", "volume": "13", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Oral L-citrulline supplementation enhances cycling time trial performance in healthy trained men: Double-blind randomized placebo-controlled 2-way crossover study.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The morphologies of ectodermal organs are shaped by appropriate combinations of several deformation modes, such as invagination and anisotropic tissue elongation. However, how multicellular dynamics are coordinated during deformation processes remains to be elucidated. Here, we developed a four-dimensional (4D) analysis system for tracking cell movement and division at a single-cell resolution in developing tooth epithelium. The expression patterns of a Fucci probe clarified the region- and stage-specific cell cycle patterns within the tooth germ, which were in good agreement with the pattern of the volume growth rate estimated from tissue-level deformation analysis. Cellular motility was higher in the regions with higher growth rates, while the mitotic orientation was significantly biased along the direction of tissue elongation in the epithelium. Further, these spatio-temporal patterns of cellular dynamics and tissue-level deformation were highly correlated with that of the activity of cofilin, which is an actin depolymerization factor, suggesting that the coordination of cellular dynamics via actin remodeling plays an important role in tooth epithelial morphogenesis. Our system enhances the understanding of how cellular behaviors are coordinated during ectodermal organogenesis, which cannot be observed from histological analyses.", "classifications": [ { "id": "Morishita", "label": "Group Morishita", "parent": "Morishita", "type": "group" }, { "id": "Morishita", "label": "Team Morishita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Ritsuko", "last_name": "Morita", "name": null }, { "creator_type": "author", "first_name": "Miho", "last_name": "Kihira", "name": null }, { "creator_type": "author", "first_name": "Yousuke", "last_name": "Nakatsu", "name": null }, { "creator_type": "author", "first_name": "Yohei", "last_name": "Nomoto", "name": null }, { "creator_type": "author", "first_name": "Miho", "last_name": "Ogawa", "name": null }, { "creator_type": "author", "first_name": "Kazumasa", "last_name": "Ohashi", "name": null }, { "creator_type": "author", "first_name": "Kensaku", "last_name": "Mizuno", "name": null }, { "creator_type": "author", "first_name": "Tetsuhiko", "last_name": "Tachikawa", "name": null }, { "creator_type": "author", "first_name": "Yukitaka", "last_name": "Ishimoto", "name": null }, { "creator_type": "author", "first_name": "Yoshihiro", "last_name": "Morishita", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Tsuji", "name": null } ], "identifiers": { "doi": { "normalized": "10.1371/journal.pone.0161336" }, "pmcid": { "normalized": "PMC5010284" }, "pmid": { "normalized": "27588418" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Division", "descriptor_ui": "D002455", "major_topic": false }, { "descriptor": "Cell Movement", "descriptor_ui": "D002465", "major_topic": false }, { "descriptor": "Cell Shape", "descriptor_ui": "D048430", "major_topic": false }, { "descriptor": "Epithelium", "descriptor_ui": "D004848", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Microscopy, Confocal", "descriptor_ui": "D018613", "major_topic": false }, { "descriptor": "Models, Biological", "descriptor_ui": "D008954", "major_topic": false }, { "descriptor": "Odontogenesis", "descriptor_ui": "D009805", "major_topic": false }, { "descriptor": "Tooth", "descriptor_ui": "D014070", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016", "date_precision": "year", "issue": "9", "normalized_date": "2016", "pages": "e0161336", "proceedings_title": null, "publisher": "", "title": "PloS one", "volume": "11", "year": 2016 }, "ssbd": { "database": [ "ssbd-database-000098" ], "repository": [ "ssbd-repos-000098" ] }, "title": "Coordination of Cellular Dynamics Contributes to Tooth Epithelium Deformations.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Uptake of poor nitrogen sources such as branched-chain amino acids is repressed in the presence of high-quality nitrogen sources such as NH4+ and glutamate (Glu), which is called nitrogen catabolite repression. Amino acid auxotrophic mutants of the fission yeast Schizosaccharomyces pombe were unable to grow on minimal medium containing NH4Cl or Glu even when adequate amounts of required amino acids were supplied. However, growth of these mutant cells was recovered in the vicinity of colonies of the prototrophic strain, suggesting that the prototrophic cells secrete some substances that can restore uptake of amino acids by an unknown mechanism. We identified the novel fatty acids, 10(R)-acetoxy-8(Z)-octadecenoic acid and 10(R)-hydroxy-8(Z)-octadecenoic acid, as secreted active substances, referred to as Nitrogen Signaling Factors (NSFs). Synthetic NSFs were also able to shift nitrogen source utilization from high-quality to poor nitrogen sources to allow adaptive growth of the fission yeast amino acid auxotrophic mutants in the presence of high-quality nitrogen sources. Finally, we demonstrated that the Agp3 amino acid transporter was involved in the adaptive growth. The data highlight a novel intra-species communication system for adaptation to environmental nutritional conditions in fission yeast.", "classifications": [ { "id": "Sodeoka", "label": "Group Sodeoka", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Xiaoying", "last_name": "Sun", "name": null }, { "creator_type": "author", "first_name": "Go", "last_name": "Hirai", "name": null }, { "creator_type": "author", "first_name": "Masashi", "last_name": "Ueki", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Hirota", "name": null }, { "creator_type": "author", "first_name": "Qianqian", "last_name": "Wang", "name": null }, { "creator_type": "author", "first_name": "Yayoi", "last_name": "Hongo", "name": null }, { "creator_type": "author", "first_name": "Takemichi", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Hitora", "name": null }, { "creator_type": "author", "first_name": "Hidekazu", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Mikiko", "last_name": "Sodeoka", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Osada", "name": null }, { "creator_type": "author", "first_name": "Makiko", "last_name": "Hamamoto", "name": null }, { "creator_type": "author", "first_name": "Minoru", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Yoko", "last_name": "Yashiroda", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/srep20856" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "26892493" } }, "mesh": [ { "descriptor": "Adaptation, Biological", "descriptor_ui": "D000220", "major_topic": false }, { "descriptor": "Amino Acid Transport Systems", "descriptor_ui": "D026905", "major_topic": false }, { "descriptor": "Amino Acids", "descriptor_ui": "D000596", "major_topic": false }, { "descriptor": "Biological Transport", "descriptor_ui": "D001692", "major_topic": false }, { "descriptor": "Catabolite Repression", "descriptor_ui": "D057465", "major_topic": true }, { "descriptor": "Fatty Acids", "descriptor_ui": "D005227", "major_topic": false }, { "descriptor": "Metabolomics", "descriptor_ui": "D055432", "major_topic": false }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": false }, { "descriptor": "Nitrogen", "descriptor_ui": "D009584", "major_topic": false }, { "descriptor": "Schizosaccharomyces", "descriptor_ui": "D012568", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016", "date_precision": "year", "issue": "", "normalized_date": "2016", "pages": "", "proceedings_title": null, "publisher": "", "title": "Scientific Reports", "volume": "6", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Identification of novel secreted fatty acids that regulate nitrogen catabolite repression in fission yeast.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Cellular energy production processes are composed of many Mg2+ dependent enzymatic reactions. In fact, dysregulation of Mg2+ homeostasis is involved in various cellular malfunctions and diseases. Recently, mitochondria, energy-producing organelles, have been known as major intracellular Mg2+ stores. Several biological stimuli alter mitochondrial Mg2+ concentration by intracellular redistribution. However, in living cells, whether mitochondrial Mg2+ alteration affect cellular energy metabolism remains unclear. Mg2+ transporter of mitochondrial inner membrane MRS2 is an essential component of mitochondrial Mg2+ uptake system. Here, we comprehensively analyzed intracellular Mg2+ levels and energy metabolism in Mrs2 knockdown (KD) cells using fluorescence imaging and metabolome analysis. Dysregulation of mitochondrial Mg2+ homeostasis disrupted ATP production via shift of mitochondrial energy metabolism and morphology. Moreover, Mrs2 KD sensitized cellular tolerance against cellular stress. These results indicate regulation of mitochondrial Mg2+via MRS2 critically decides cellular energy status and cell vulnerability via regulation of mitochondrial Mg2+ level in response to physiological stimuli.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Ryu", "last_name": "Yamanaka", "name": null }, { "creator_type": "author", "first_name": "Sho", "last_name": "Tabata", "name": null }, { "creator_type": "author", "first_name": "Yutaka", "last_name": "Shindo", "name": null }, { "creator_type": "author", "first_name": "Kohji", "last_name": "Hotta", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Kotaro", "last_name": "Oka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/srep30027" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "27458051" } }, "mesh": [ { "descriptor": "Biological Transport", "descriptor_ui": "D001692", "major_topic": false }, { "descriptor": "Cation Transport Proteins", "descriptor_ui": "D027682", "major_topic": false }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Cell Physiological Phenomena", "descriptor_ui": "D002468", "major_topic": false }, { "descriptor": "Energy Metabolism", "descriptor_ui": "D004734", "major_topic": false }, { "descriptor": "HeLa Cells", "descriptor_ui": "D006367", "major_topic": false }, { "descriptor": "Homeostasis", "descriptor_ui": "D006706", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Magnesium", "descriptor_ui": "D008274", "major_topic": false }, { "descriptor": "Membrane Potential, Mitochondrial", "descriptor_ui": "D053078", "major_topic": false }, { "descriptor": "Mitochondria", "descriptor_ui": "D008928", "major_topic": false }, { "descriptor": "Mitochondrial Proteins", "descriptor_ui": "D024101", "major_topic": false }, { "descriptor": "RNA Interference", "descriptor_ui": "D034622", "major_topic": false }, { "descriptor": "RNA, Small Interfering", "descriptor_ui": "D034741", "major_topic": false }, { "descriptor": "Stress, Physiological", "descriptor_ui": "D013312", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016", "date_precision": "year", "issue": "", "normalized_date": "2016", "pages": "", "proceedings_title": null, "publisher": "", "title": "Scientific Reports", "volume": "6", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Mitochondrial Mg2+ homeostasis decides cellular energy metabolism and vulnerability to stress.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Reactive oxygen species (ROS) produced by NADPH oxidase 2 (Nox2) function as key mediators of mechanotransduction during both physiological adaptation to mechanical load and maladaptive remodeling of the heart. This is despite low levels of cardiac Nox2 expression. The mechanism underlying the transition from adaptation to maladaptation remains obscure, however. We demonstrate that transient receptor potential canonical 3 (TRPC3), a Ca2+-permeable channel, acts as a positive regulator of ROS (PRROS) in cardiomyocytes, and specifically regulates pressure overload-induced maladaptive cardiac remodeling in mice. TRPC3 physically interacts with Nox2 at specific C-terminal sites, thereby protecting Nox2 from proteasome-dependent degradation and amplifying Ca2+-dependent Nox2 activation through TRPC3-mediated background Ca2+ entry. Nox2 also stabilizes TRPC3 proteins to enhance TRPC3 channel activity. Expression of TRPC3 C-terminal polypeptide abolished TRPC3-regulated ROS production by disrupting TRPC3-Nox2 interaction, without affecting TRPC3-mediated Ca2+ influx. The novel TRPC3 function as a PRROS provides a mechanistic explanation for how diastolic Ca2+ influx specifically encodes signals to induce ROS-mediated maladaptive remodeling and offers new therapeutic possibilities.", "classifications": [ { "id": "Nishida", "label": "Group Nishida", "parent": "Nishida", "type": "group" }, { "id": "Nishimura", "label": "Group Nishimura", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Naoyuki", "last_name": "Kitajima", "name": null }, { "creator_type": "author", "first_name": "Takuro", "last_name": "Numaga-Tomita", "name": null }, { "creator_type": "author", "first_name": "Masahiko", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Kuroda", "name": null }, { "creator_type": "author", "first_name": "Akiyuki", "last_name": "Nishimura", "name": null }, { "creator_type": "author", "first_name": "Kei", "last_name": "Miyano", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Yasuda", "name": null }, { "creator_type": "author", "first_name": "Koichiro", "last_name": "Kuwahara", "name": null }, { "creator_type": "author", "first_name": "Yoji", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Tomomi", "last_name": "Ide", "name": null }, { "creator_type": "author", "first_name": "Lutz", "last_name": "Birnbaumer", "name": null }, { "creator_type": "author", "first_name": "Hideki", "last_name": "Sumimoto", "name": null }, { "creator_type": "author", "first_name": "Yasuo", "last_name": "Mori", "name": null }, { "creator_type": "author", "first_name": "Motohiro", "last_name": "Nishida", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/srep37001" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "27833156" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Calcium Signaling", "descriptor_ui": "D020013", "major_topic": false }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "CHO Cells", "descriptor_ui": "D016466", "major_topic": false }, { "descriptor": "Cricetulus", "descriptor_ui": "D003412", "major_topic": false }, { "descriptor": "Cytochrome b Group", "descriptor_ui": "D003573", "major_topic": false }, { "descriptor": "Diastole", "descriptor_ui": "D003971", "major_topic": false }, { "descriptor": "Enzyme Activation", "descriptor_ui": "D004789", "major_topic": false }, { "descriptor": "HEK293 Cells", "descriptor_ui": "D057809", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mice, 129 Strain", "descriptor_ui": "D057507", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Myocytes, Cardiac", "descriptor_ui": "D032383", "major_topic": false }, { "descriptor": "NADPH Oxidase 2", "descriptor_ui": "D000074662", "major_topic": false }, { "descriptor": "NADPH Oxidases", "descriptor_ui": "D019255", "major_topic": false }, { "descriptor": "Proteasome Endopeptidase Complex", "descriptor_ui": "D046988", "major_topic": false }, { "descriptor": "Protein Interaction Mapping", "descriptor_ui": "D025941", "major_topic": false }, { "descriptor": "Protein Stability", "descriptor_ui": "D055550", "major_topic": false }, { "descriptor": "Rats, Sprague-Dawley", "descriptor_ui": "D017207", "major_topic": false }, { "descriptor": "Reactive Oxygen Species", "descriptor_ui": "D017382", "major_topic": false }, { "descriptor": "Recombinant Fusion Proteins", "descriptor_ui": "D011993", "major_topic": false }, { "descriptor": "Stress, Mechanical", "descriptor_ui": "D013314", "major_topic": false }, { "descriptor": "TRPC Cation Channels", "descriptor_ui": "D050052", "major_topic": false }, { "descriptor": "TRPC6 Cation Channel", "descriptor_ui": "D000074287", "major_topic": false }, { "descriptor": "Ventricular Dysfunction, Left", "descriptor_ui": "D018487", "major_topic": false }, { "descriptor": "Ventricular Remodeling", "descriptor_ui": "D020257", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016", "date_precision": "year", "issue": "", "normalized_date": "2016", "pages": "", "proceedings_title": null, "publisher": "", "title": "Scientific Reports", "volume": "6", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "TRPC3 positively regulates reactive oxygen species driving maladaptive cardiac remodeling.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Plasmonics, which are based on the collective oscillation of electrons due to light excitation, involve strongly enhanced local electric fields and thus have potential applications in nonlinear optics, which requires extraordinary optical intensity. One of the most studied nonlinearities in plasmonics is nonlinear absorption, including saturation and reverse saturation behaviors. Although scattering and absorption in nanoparticles are closely correlated by the Mie theory, there has been no report of nonlinearities in plasmonic scattering until very recently. Last year, not only saturation, but also reverse saturation of scattering in an isolated plasmonic particle was demonstrated for the first time. The results showed that saturable scattering exhibits clear wavelength dependence, which seems to be directly linked to the localized surface plasmon resonance (LSPR). Combined with the intensity-dependent measurements, the results suggest the possibility of a common mechanism underlying the nonlinear behaviors of scattering and absorption. These nonlinearities of scattering from a single gold nanosphere (GNS) are widely applicable, including in super-resolution microscopy and optical switches. In this paper, it is described in detail how to measure nonlinearity of scattering in a single GNP and how to employ the super-resolution technique to enhance the optical imaging resolution based on saturable scattering. This discovery features the first super-resolution microscopy based on nonlinear scattering, which is a novel non-bleaching contrast method that can achieve a resolution as low as l/8 and will potentially be useful in biomedicine and material studies.", "classifications": [ { "id": "Fujita", "label": "Group Fujita", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Hsuan", "last_name": "Lee", "name": null }, { "creator_type": "author", "first_name": "Kuan-Yu", "last_name": "Li", "name": null }, { "creator_type": "author", "first_name": "Yen-Ta", "last_name": "Huang", "name": null }, { "creator_type": "author", "first_name": "Po-Ting", "last_name": "Shen", "name": null }, { "creator_type": "author", "first_name": "Gitanjal", "last_name": "Deka", "name": null }, { "creator_type": "author", "first_name": "Ryosuke", "last_name": "Oketani", "name": null }, { "creator_type": "author", "first_name": "Yasuo", "last_name": "Yonemaru", "name": null }, { "creator_type": "author", "first_name": "Masahito", "last_name": "Yamanaka", "name": null }, { "creator_type": "author", "first_name": "Katsumasa", "last_name": "Fujita", "name": null }, { "creator_type": "author", "first_name": "Shi-Wei", "last_name": "Chu", "name": null } ], "identifiers": { "doi": { "normalized": "10.3791/53338" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "26780248" } }, "mesh": [ { "descriptor": "Electrons", "descriptor_ui": "D004583", "major_topic": false }, { "descriptor": "Gold", "descriptor_ui": "D006046", "major_topic": false }, { "descriptor": "Light", "descriptor_ui": "D008027", "major_topic": false }, { "descriptor": "Metal Nanoparticles", "descriptor_ui": "D053768", "major_topic": false }, { "descriptor": "Nonlinear Dynamics", "descriptor_ui": "D017711", "major_topic": false }, { "descriptor": "Optical Imaging", "descriptor_ui": "D061848", "major_topic": false }, { "descriptor": "Optics and Photonics", "descriptor_ui": "D055095", "major_topic": false }, { "descriptor": "Scattering, Radiation", "descriptor_ui": "D012542", "major_topic": false }, { "descriptor": "Surface Plasmon Resonance", "descriptor_ui": "D020349", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016", "date_precision": "year", "issue": "107", "normalized_date": "2016", "pages": "", "proceedings_title": null, "publisher": "", "title": "Journal of Visualized Experiments : JoVE", "volume": "", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Measurement of Scattering Nonlinearities from a Single Plasmonic Nanoparticle.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Signaling networks are made up of limited numbers of molecules and yet can code information that controls different cellular states through temporal patterns and a combination of signaling molecules. In this study, we used a data-driven modeling approach, the Laguerre filter with partial least square regression, to describe how temporal and combinatorial patterns of signaling molecules are decoded by their downstream targets. The Laguerre filter is a time series model used to represent a nonlinear system based on Volterra series expansion. Furthermore, with this approach, each component of the Volterra series expansion is expanded by Laguerre basis functions. We combined two approaches, application of a Laguerre filter and partial least squares (PLS) regression, and applied the combined approach to analysis of a signal transduction network. We applied the Laguerre filter with PLS regression to identify input and output (IO) relationships between MAP kinases and the products of immediate early genes (IEGs). We found that Laguerre filter with PLS regression performs better than Laguerre filter with ordinary regression for the reproduction of a time series of IEGs. Analysis of the nonlinear characteristics extracted using the Laguerre filter revealed a priming effect of ERK and CREB on c-FOS induction. Specifically, we found that the effects of a first pulse of ERK enhance the subsequent effects on c-FOS induction of treatment with a second pulse of ERK, a finding consistent with prior molecular biological knowledge. The variable importance of projections and output loadings in PLS regression predicted the upstream dependency of each IEG. Thus, a Laguerre filter with partial least square regression approach appears to be a powerful method to find the processing mechanism of temporal patterns and combination of signaling molecules by their downstream gene expression.", "classifications": [ { "id": "Kuroda", "label": "Group Kuroda", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Takamasa", "last_name": "Kudo", "name": null }, { "creator_type": "author", "first_name": "Shinsuke", "last_name": "Uda", "name": null }, { "creator_type": "author", "first_name": "Takaho", "last_name": "Tsuchiya", "name": null }, { "creator_type": "author", "first_name": "Takumi", "last_name": "Wada", "name": null }, { "creator_type": "author", "first_name": "Yasuaki", "last_name": "Karasawa", "name": null }, { "creator_type": "author", "first_name": "Masashi", "last_name": "Fujii", "name": null }, { "creator_type": "author", "first_name": "Takeshi H.", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Kuroda", "name": null } ], "identifiers": { "doi": { "normalized": "10.1371/journal.pone.0160548" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "27513954" } }, "mesh": [ { "descriptor": "Cyclic AMP Response Element-Binding Protein", "descriptor_ui": "D017362", "major_topic": false }, { "descriptor": "Extracellular Signal-Regulated MAP Kinases", "descriptor_ui": "D048049", "major_topic": false }, { "descriptor": "Gene Expression Regulation", "descriptor_ui": "D005786", "major_topic": false }, { "descriptor": "Least-Squares Analysis", "descriptor_ui": "D016018", "major_topic": false }, { "descriptor": "MAP Kinase Signaling System", "descriptor_ui": "D020935", "major_topic": false }, { "descriptor": "Nonlinear Dynamics", "descriptor_ui": "D017711", "major_topic": true }, { "descriptor": "Proto-Oncogene Proteins c-fos", "descriptor_ui": "D016760", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016", "date_precision": "year", "issue": "8", "normalized_date": "2016", "pages": "", "proceedings_title": null, "publisher": "", "title": "PLoS ONE", "volume": "11", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Laguerre Filter Analysis with Partial Least Square Regression Reveals a Priming Effect of ERK and CREB on c-FOS Induction.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Non-muscle invasive (superficial) bladder cancer is a low-grade malignancy with good prognosis, while muscle invasive (invasive) bladder cancer is a high-grade malignancy with poor prognosis. N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) induces superficial bladder cancers with papillary morphology in rats and invasive bladder cancers with infiltrating phenotype in mice. In this study, we analyzed genomic landscapes of rodent BBN-induced bladder cancers using array-based comparative genomic hybridization (array CGH). While no significant copy number alterations were detected in superficial bladder tumors in rats, copy number gains in chromosomal regions 2D-E1, 7qA3, 9F2, and 11C-D were detected in invasive bladder tumors in mice. Amplification of representative genes located on 2D-E1 and 7qA3 chromosomal regions was confirmed by quantitative PCR. Cyp2a22 and Cyp2a5 genes but not Cyp2g1, Cyp2a12, and Rab4b genes on mouse chromosome 7qA3 were amplified in invasive bladder cancers. Although the human ortholog gene of Cyp2a22 has not been confirmed, the mouse Cyp2a5 gene is the ortholog of the human CYP2A6 gene located in chromosomal region 19q13.2, and CYP2A6 was identified by database search as one of the closest human homolog to mouse Cyp2a22. Considering a possibility that this region may be related to mouse 7qA3, we analyzed CYP2A6 copy number and expression in human bladder cancer using cell lines and resected tumor specimens. Although only one of eight cell lines showed more than one copy increase of the CYP2A6 gene, CYP2A6 amplification was detected in six out of 18 primary bladder tumors where it was associated with the invasive phenotype. Immunohistochemical analyses of 118 primary bladder tumors revealed that CYP2A6 protein expression was also higher in invasive tumors, especially in those of the scattered type. Together, these findings indicate that the amplification and overexpression of the CYP2A6 gene are characteristic of human bladder cancers with increased malignancy and that CYP2A6 can be a candidate prognostic biomarker in this type of cancer.", "classifications": [ { "id": "Okamoto", "label": "Group Okamoto", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Kazuhiro", "last_name": "Kanemoto", "name": null }, { "creator_type": "author", "first_name": "Katsuhiro", "last_name": "Fukuta", "name": null }, { "creator_type": "author", "first_name": "Noriyasu", "last_name": "Kawai", "name": null }, { "creator_type": "author", "first_name": "Keiichi", "last_name": "Tozawa", "name": null }, { "creator_type": "author", "first_name": "Masako", "last_name": "Ochiai", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Okamoto", "name": null }, { "creator_type": "author", "first_name": "Sumiko", "last_name": "Ohnami", "name": null }, { "creator_type": "author", "first_name": "Hiromi", "last_name": "Sakamoto", "name": null }, { "creator_type": "author", "first_name": "Teruhiko", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Yae", "last_name": "Kanai", "name": null }, { "creator_type": "author", "first_name": "Masaru", "last_name": "Katoh", "name": null }, { "creator_type": "author", "first_name": "Takahiro", "last_name": "Yasui", "name": null }, { "creator_type": "author", "first_name": "Kenjiro", "last_name": "Kohri", "name": null }, { "creator_type": "author", "first_name": "Tadao", "last_name": "Kakizoe", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Nakagama", "name": null } ], "identifiers": { "doi": { "normalized": "10.1371/journal.pone.0167374" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "27902773" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Aryl Hydrocarbon Hydroxylases", "descriptor_ui": "D001189", "major_topic": false }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Cytochrome P-450 CYP2A6", "descriptor_ui": "D065637", "major_topic": false }, { "descriptor": "Cytochrome P450 Family 2", "descriptor_ui": "D000072467", "major_topic": false }, { "descriptor": "Gene Amplification", "descriptor_ui": "D005784", "major_topic": true }, { "descriptor": "Gene Dosage", "descriptor_ui": "D018628", "major_topic": false }, { "descriptor": "Gene Expression Regulation, Neoplastic", "descriptor_ui": "D015972", "major_topic": true }, { "descriptor": "Genomics", "descriptor_ui": "D023281", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Neoplasm Invasiveness", "descriptor_ui": "D009361", "major_topic": false }, { "descriptor": "Phenotype", "descriptor_ui": "D010641", "major_topic": true }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Synteny", "descriptor_ui": "D026801", "major_topic": false }, { "descriptor": "Urinary Bladder Neoplasms", "descriptor_ui": "D001749", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016", "date_precision": "year", "issue": "11", "normalized_date": "2016", "pages": "", "proceedings_title": null, "publisher": "", "title": "PLoS ONE", "volume": "11", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Genomic Landscape of Experimental Bladder Cancer in Rodents and Its Application to Human Bladder Cancer: Gene Amplification and Potential Overexpression of Cyp2a5/CYP2A6 Are Associated with the Invasive Phenotype.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Canonical Wnt/β-catenin signalling is essential for maintaining intestinal stem cells, and its constitutive activation has been implicated in colorectal carcinogenesis. We and others have previously identified Traf2- and Nck-interacting kinase (TNIK) as an essential regulatory component of the T-cell factor-4 and β-catenin transcriptional complex. Consistent with this, Tnik-deficient mice are resistant to azoxymethane-induced colon tumorigenesis, and Tnik−/−/Apcmin/+ mutant mice develop significantly fewer intestinal tumours. Here we report the first orally available small-molecule TNIK inhibitor, NCB-0846, having anti-Wnt activity. X-ray co-crystal structure analysis reveals that NCB-0846 binds to TNIK in an inactive conformation, and this binding mode seems to be essential for Wnt inhibition. NCB-0846 suppresses Wnt-driven intestinal tumorigenesis in Apcmin/+ mice and the sphere- and tumour-forming activities of colorectal cancer cells. TNIK is required for the tumour-initiating function of colorectal cancer stem cells. Its inhibition is a promising therapeutic approach.", "classifications": [ { "id": "Okamoto", "label": "Group Okamoto", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Mari", "last_name": "Masuda", "name": null }, { "creator_type": "author", "first_name": "Yuko", "last_name": "Uno", "name": null }, { "creator_type": "author", "first_name": "Naomi", "last_name": "Ohbayashi", "name": null }, { "creator_type": "author", "first_name": "Hirokazu", "last_name": "Ohata", "name": null }, { "creator_type": "author", "first_name": "Ayako", "last_name": "Mimata", "name": null }, { "creator_type": "author", "first_name": "Mutsuko", "last_name": "Kukimoto-Niino", "name": null }, { "creator_type": "author", "first_name": "Hideki", "last_name": "Moriyama", "name": null }, { "creator_type": "author", "first_name": "Shigeki", "last_name": "Kashimoto", "name": null }, { "creator_type": "author", "first_name": "Tomoko", "last_name": "Inoue", "name": null }, { "creator_type": "author", "first_name": "Naoko", "last_name": "Goto", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Okamoto", "name": null }, { "creator_type": "author", "first_name": "Mikako", "last_name": "Shirouzu", "name": null }, { "creator_type": "author", "first_name": "Masaaki", "last_name": "Sawa", "name": null }, { "creator_type": "author", "first_name": "Tesshi", "last_name": "Yamada", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/ncomms12586" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "27562646" } }, "mesh": [ { "descriptor": "Adenomatous Polyposis Coli Protein", "descriptor_ui": "D025601", "major_topic": false }, { "descriptor": "Administration, Oral", "descriptor_ui": "D000284", "major_topic": false }, { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Azoxymethane", "descriptor_ui": "D001397", "major_topic": false }, { "descriptor": "beta Catenin", "descriptor_ui": "D051176", "major_topic": false }, { "descriptor": "Carcinogenesis", "descriptor_ui": "D063646", "major_topic": false }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Cell Proliferation", "descriptor_ui": "D049109", "major_topic": false }, { "descriptor": "Cell Transformation, Neoplastic", "descriptor_ui": "D002471", "major_topic": false }, { "descriptor": "Colorectal Neoplasms", "descriptor_ui": "D015179", "major_topic": false }, { "descriptor": "Crystallography, X-Ray", "descriptor_ui": "D018360", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Germinal Center Kinases", "descriptor_ui": "D000081410", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Imidazoles", "descriptor_ui": "D007093", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred BALB C", "descriptor_ui": "D008807", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Mice, Nude", "descriptor_ui": "D008819", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": false }, { "descriptor": "Neoplastic Stem Cells", "descriptor_ui": "D014411", "major_topic": false }, { "descriptor": "Protein Binding", "descriptor_ui": "D011485", "major_topic": false }, { "descriptor": "Protein Kinase Inhibitors", "descriptor_ui": "D047428", "major_topic": false }, { "descriptor": "Protein Serine-Threonine Kinases", "descriptor_ui": "D017346", "major_topic": false }, { "descriptor": "Quinazolines", "descriptor_ui": "D011799", "major_topic": false }, { "descriptor": "Recombinant Proteins", "descriptor_ui": "D011994", "major_topic": false }, { "descriptor": "Ubiquitin-Protein Ligases", "descriptor_ui": "D044767", "major_topic": false }, { "descriptor": "Wnt Proteins", "descriptor_ui": "D051153", "major_topic": false }, { "descriptor": "Wnt Signaling Pathway", "descriptor_ui": "D060449", "major_topic": false }, { "descriptor": "Xenograft Model Antitumor Assays", "descriptor_ui": "D023041", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016", "date_precision": "year", "issue": "", "normalized_date": "2016", "pages": "", "proceedings_title": null, "publisher": "", "title": "Nature Communications", "volume": "7", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "TNIK inhibition abrogates colorectal cancer stemness.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "External cues that dictate the direction of cell migration are likely dynamic during many biological processes such as embryonic development and wound healing. Until recently, how cells integrate spatial and temporal information to determine the direction of migration has remained elusive. In Dictyostelium discoideum, the chemoattractant cAMP that directs cell aggregation propagates as periodic waves. In light of the fact that any temporally evolving complex signals, in principle, can be expressed as a sum of sinusoidal functions with various frequencies, the Dictyostelium system serves as a minimal example, where the dynamic signal is in the simplest form of near sinusoidal wave with one dominant frequency. Here, we describe a method to emulate the traveling waves in a fluidics device. The text provides step-by-step instructions on the device setup and describes ways to analyze the acquired data. These include quantification of membrane translocation of fluorescently labeled proteins in individual Dictyostelium cells and estimation of exogenous cAMP profiles. The described approach has already helped decipher spatial and temporal aspects of chemotactic sensing in Dictyostelium. More specifically, it allowed one to discriminate the temporal and the spatial sensing aspects of directional sensing. With some modifications, one should be able to implement similar analysis in other cell types.", "classifications": [ { "id": "Sawai", "label": "Group Sawai", "parent": "Sawai", "type": "group" }, { "id": "Sawai", "label": "Team Sawai", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Akihiko", "last_name": "Nakajima", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Sawai", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/978-1-4939-3480-5_8" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "27271897" } }, "mesh": [ { "descriptor": "Algorithms", "descriptor_ui": "D000465", "major_topic": false }, { "descriptor": "Cell Culture Techniques", "descriptor_ui": "D018929", "major_topic": false }, { "descriptor": "Cell Membrane", "descriptor_ui": "D002462", "major_topic": false }, { "descriptor": "Cell Movement", "descriptor_ui": "D002465", "major_topic": false }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Chemotaxis", "descriptor_ui": "D002633", "major_topic": true }, { "descriptor": "Cyclic AMP", "descriptor_ui": "D000242", "major_topic": false }, { "descriptor": "Dictyostelium", "descriptor_ui": "D004023", "major_topic": false }, { "descriptor": "Models, Biological", "descriptor_ui": "D008954", "major_topic": false }, { "descriptor": "Protein Transport", "descriptor_ui": "D021381", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016", "date_precision": "year", "issue": "", "normalized_date": "2016", "pages": "107-122", "proceedings_title": null, "publisher": "", "title": "Methods in molecular biology (Clifton, N.J.)", "volume": "1407", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Dissecting Spatial and Temporal Sensing in Dictyostelium Chemotaxis Using a Wave Gradient Generator.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Because of their exceptional local-field enhancement and ultrasmall mode volume, plasmonic components can integrate photonics and electronics at nanoscale, and active control of plasmons is the key. However, all-optical modulation of plasmonic response with nanometer mode volume and unity modulation depth is still lacking. Here we show that scattering from a plasmonic nanoparticle, whose volume is smaller than 0.001 μm3, can be optically switched off with less than 100 μW power. Over 80% modulation depth is observed, and shows no degradation after repetitive switching. The spectral bandwidth approaches 100 nm. The underlying mechanism is suggested to be photothermal effects, and the effective single-particle nonlinearity reaches nearly 10−9 m2/W, which is to our knowledge the largest record of metallic materials to date. As a novel application, the non-bleaching and unlimitedly switchable scattering is used to enhance optical resolution to λ/5 (λ/9 after deconvolution), with 100-fold less intensity requirement compared to similar superresolution techniques. Our work not only opens up a new field of ultrasmall all-optical control based on scattering from a single nanoparticle, but also facilitates superresolution imaging for long-term observation.", "classifications": [ { "id": "Fujita", "label": "Group Fujita", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Hsueh-Yu", "last_name": "Wu", "name": null }, { "creator_type": "author", "first_name": "Yen-Ta", "last_name": "Huang", "name": null }, { "creator_type": "author", "first_name": "Po-Ting", "last_name": "Shen", "name": null }, { "creator_type": "author", "first_name": "Hsuan", "last_name": "Lee", "name": null }, { "creator_type": "author", "first_name": "Ryosuke", "last_name": "Oketani", "name": null }, { "creator_type": "author", "first_name": "Yasuo", "last_name": "Yonemaru", "name": null }, { "creator_type": "author", "first_name": "Masahito", "last_name": "Yamanaka", "name": null }, { "creator_type": "author", "first_name": "Satoru", "last_name": "Shoji", "name": null }, { "creator_type": "author", "first_name": "Kung-Hsuan", "last_name": "Lin", "name": null }, { "creator_type": "author", "first_name": "Chih-Wei", "last_name": "Chang", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Kawata", "name": null }, { "creator_type": "author", "first_name": "Katsumasa", "last_name": "Fujita", "name": null }, { "creator_type": "author", "first_name": "Shi-Wei", "last_name": "Chu", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/srep24293" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "27063920" } }, "mesh": [], "publication": { "conference_name": null, "date": "2016", "date_precision": "year", "issue": "", "normalized_date": "2016", "pages": "", "proceedings_title": null, "publisher": "", "title": "Scientific Reports", "volume": "6", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Ultrasmall all-optical plasmonic switch and its application to superresolution imaging.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The Drosophila mutant tko25t exhibits a deficiency of mitochondrial protein synthesis, leading to a global insufficiency of respiration and oxidative phosphorylation. This entrains an organismal phenotype of developmental delay and sensitivity to seizures induced by mechanical stress. We found that the mutant phenotype is exacerbated in a dose-dependent fashion by high dietary sugar levels. tko25t larvae were found to exhibit severe metabolic abnormalities that were further accentuated by high-sugar diet. These include elevated pyruvate and lactate, decreased ATP and NADPH. Dietary pyruvate or lactate supplementation phenocopied the effects of high sugar. Based on tissue-specific rescue, the crucial tissue in which this metabolic crisis initiates is the gut. It is accompanied by down-regulation of the apparatus of cytosolic protein synthesis and secretion at both the RNA and post-translational levels, including a novel regulation of S6 kinase at the protein level.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Esko", "last_name": "Kemppainen", "name": null }, { "creator_type": "author", "first_name": "Jack", "last_name": "George", "name": null }, { "creator_type": "author", "first_name": "Gorkem", "last_name": "Garipler", "name": null }, { "creator_type": "author", "first_name": "Tea", "last_name": "Tuomela", "name": null }, { "creator_type": "author", "first_name": "Essi", "last_name": "Kiviranta", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Cory D.", "last_name": "Dunn", "name": null }, { "creator_type": "author", "first_name": "Howard T.", "last_name": "Jacobs", "name": null } ], "identifiers": { "doi": { "normalized": "10.1371/journal.pone.0145836" }, "pmcid": { "normalized": "PMC4728084" }, "pmid": { "normalized": "26812173" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Diet", "descriptor_ui": "D004032", "major_topic": true }, { "descriptor": "Dietary Sucrose", "descriptor_ui": "D019422", "major_topic": false }, { "descriptor": "Disease Models, Animal", "descriptor_ui": "D004195", "major_topic": false }, { "descriptor": "Drosophila", "descriptor_ui": "D004330", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Lactic Acid", "descriptor_ui": "D019344", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mitochondria", "descriptor_ui": "D008928", "major_topic": false }, { "descriptor": "Pyruvic Acid", "descriptor_ui": "D019289", "major_topic": false }, { "descriptor": "Reactive Oxygen Species", "descriptor_ui": "D017382", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016", "date_precision": "year", "issue": "1", "normalized_date": "2016", "pages": "e0145836", "proceedings_title": null, "publisher": "", "title": "PloS one", "volume": "11", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Mitochondrial Dysfunction Plus High-Sugar Diet Provokes a Metabolic Crisis That Inhibits Growth.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Structural cardiac remodeling, accompanying cytoskeletal reorganization of cardiac cells, is a major clinical outcome of diastolic heart failure. A highly local Ca2+ influx across the plasma membrane has been suggested to code signals to induce Rho GTPase-mediated fibrosis, but it is obscure how the heart specifically decodes the local Ca2+ influx as a cytoskeletal reorganizing signal under the conditions of the rhythmic Ca2+ handling required for pump function. We found that an inhibition of transient receptor potential canonical 3 (TRPC3) channel activity exhibited resistance to Rho-mediated maladaptive fibrosis in pressure-overloaded mouse hearts. Proteomic analysis revealed that microtubule-associated Rho guanine nucleotide exchange factor, GEF-H1, participates in TRPC3-mediated RhoA activation induced by mechanical stress in cardiomyocytes and transforming growth factor (TGF) β stimulation in cardiac fibroblasts. We previously revealed that TRPC3 functionally interacts with microtubule-associated NADPH oxidase (Nox) 2, and inhibition of Nox2 attenuated mechanical stretch-induced GEF-H1 activation in cardiomyocytes. Finally, pharmacological TRPC3 inhibition significantly suppressed fibrotic responses in human cardiomyocytes and cardiac fibroblasts. These results strongly suggest that microtubule-localized TRPC3-GEF-H1 axis mediates fibrotic responses commonly in cardiac myocytes and fibroblasts induced by physico-chemical stimulation.", "classifications": [ { "id": "Nishida", "label": "Group Nishida", "parent": "Nishida", "type": "group" }, { "id": "Nishimura", "label": "Group Nishimura", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Takuro", "last_name": "Numaga-Tomita", "name": null }, { "creator_type": "author", "first_name": "Naoyuki", "last_name": "Kitajima", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Kuroda", "name": null }, { "creator_type": "author", "first_name": "Akiyuki", "last_name": "Nishimura", "name": null }, { "creator_type": "author", "first_name": "Kei", "last_name": "Miyano", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Yasuda", "name": null }, { "creator_type": "author", "first_name": "Koichiro", "last_name": "Kuwahara", "name": null }, { "creator_type": "author", "first_name": "Yoji", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Tomomi", "last_name": "Ide", "name": null }, { "creator_type": "author", "first_name": "Lutz", "last_name": "Birnbaumer", "name": null }, { "creator_type": "author", "first_name": "Hideki", "last_name": "Sumimoto", "name": null }, { "creator_type": "author", "first_name": "Yasuo", "last_name": "Mori", "name": null }, { "creator_type": "author", "first_name": "Motohiro", "last_name": "Nishida", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/srep39383" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "27991560" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Fibroblasts", "descriptor_ui": "D005347", "major_topic": false }, { "descriptor": "Fibrosis", "descriptor_ui": "D005355", "major_topic": false }, { "descriptor": "Heart", "descriptor_ui": "D006321", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Microtubules", "descriptor_ui": "D008870", "major_topic": false }, { "descriptor": "Myocytes, Cardiac", "descriptor_ui": "D032383", "major_topic": false }, { "descriptor": "NADPH Oxidases", "descriptor_ui": "D019255", "major_topic": false }, { "descriptor": "Proteomics", "descriptor_ui": "D040901", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Rho Guanine Nucleotide Exchange Factors", "descriptor_ui": "D064067", "major_topic": false }, { "descriptor": "rhoA GTP-Binding Protein", "descriptor_ui": "D020742", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Transforming Growth Factor beta", "descriptor_ui": "D016212", "major_topic": false }, { "descriptor": "TRPC Cation Channels", "descriptor_ui": "D050052", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016", "date_precision": "year", "issue": "", "normalized_date": "2016", "pages": "", "proceedings_title": null, "publisher": "", "title": "Scientific Reports", "volume": "6", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "TRPC3-GEF-H1 axis mediates pressure overload-induced cardiac fibrosis.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Associations between alcohol consumption and type 2 diabetes risk are inconsistent in epidemiologic studies. This study investigated the associations of ADH1B and ALDH2 polymorphisms with fasting blood glucose levels, and the impact of the associations of alcohol consumption with fasting blood glucose levels in Japanese individuals. This cross-sectional study included 907 men and 912 women, aged 35-69 years. The subjects were selected from among the Japan Multi-institutional Collaborative Cohort study across six areas of Japan. The ADH1B and ALDH2 polymorphisms were genotyped by Invader Assays. The ALDH2 Glu504Lys genotypes were associated with different levels of fasting blood glucose in men (P = 0.04). Mean fasting glucose level was positively associated with alcohol consumption in men with the ALDH2 504 Lys allele (P trend = 0.02), but not in men with the ALDH2 504Glu/Glu genotype (P trend = 0.45), resulting in no statistically significant interaction (P = 0.38). Alcohol consumption was associated with elevated fasting blood glucose levels compared with non-consumers in men (P trend = 0.002). The ADH1B Arg48His polymorphism was not associated with FBG levels overall or after stratification for alcohol consumption. These findings suggest that the ALDH2 polymorphism is associated with different levels of fasting blood glucose through alcohol consumption in Japanese men. The interaction of ALDH2 polymorphisms in the association between alcohol consumption and fasting blood glucose warrants further investigation.", "classifications": [ { "id": "Tanaka", "label": "Group Tanaka", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Guang", "last_name": "Yin", "name": null }, { "creator_type": "author", "first_name": "Mariko", "last_name": "Naito", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Wakai", "name": null }, { "creator_type": "author", "first_name": "Emi", "last_name": "Morita", "name": null }, { "creator_type": "author", "first_name": "Sayo", "last_name": "Kawai", "name": null }, { "creator_type": "author", "first_name": "Nobuyuki", "last_name": "Hamajima", "name": null }, { "creator_type": "author", "first_name": "Sadao", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Yoshikuni", "last_name": "Kita", "name": null }, { "creator_type": "author", "first_name": "Toshiro", "last_name": "Takezaki", "name": null }, { "creator_type": "author", "first_name": "Keitaro", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Makiko", "last_name": "Morita", "name": null }, { "creator_type": "author", "first_name": "Hirokazu", "last_name": "Uemura", "name": null }, { "creator_type": "author", "first_name": "Etsuko", "last_name": "Ozaki", "name": null }, { "creator_type": "author", "first_name": "Satoyo", "last_name": "Hosono", "name": null }, { "creator_type": "author", "first_name": "Haruo", "last_name": "Mikami", "name": null }, { "creator_type": "author", "first_name": "Michiaki", "last_name": "Kubo", "name": null }, { "creator_type": "author", "first_name": "Hideo", "last_name": "Tanaka", "name": null } ], "identifiers": { "doi": { "normalized": null }, "pmcid": { "normalized": "PMC4885818" }, "pmid": { "normalized": "27303105" } }, "mesh": [ { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Alcohol Dehydrogenase", "descriptor_ui": "D000426", "major_topic": false }, { "descriptor": "Alcohol Drinking", "descriptor_ui": "D000428", "major_topic": false }, { "descriptor": "Aldehyde Dehydrogenase, Mitochondrial", "descriptor_ui": "D000071396", "major_topic": false }, { "descriptor": "Blood Glucose", "descriptor_ui": "D001786", "major_topic": false }, { "descriptor": "Cohort Studies", "descriptor_ui": "D015331", "major_topic": false }, { "descriptor": "Cross-Sectional Studies", "descriptor_ui": "D003430", "major_topic": false }, { "descriptor": "Diabetes Mellitus, Type 2", "descriptor_ui": "D003924", "major_topic": false }, { "descriptor": "Fasting", "descriptor_ui": "D005215", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Genotype", "descriptor_ui": "D005838", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Japan", "descriptor_ui": "D007564", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Polymorphism, Genetic", "descriptor_ui": "D011110", "major_topic": true } ], "publication": { "conference_name": null, "date": "2016 May", "date_precision": "unknown", "issue": "2", "normalized_date": null, "pages": "183-193", "proceedings_title": null, "publisher": "", "title": "Nagoya journal of medical science", "volume": "78", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "ALDH2 polymorphism is associated with fasting blood glucose through alcohol consumption in Japanese men.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The accuracy of replicating the genetic code is fundamental. DNA repair mechanisms protect the fidelity of the genome ensuring a low error rate between generations. This sustains the similarity of individuals whilst providing a repertoire of variants for evolution. The mutation rate in the human genome has recently been measured to be 50-70 de novo single nucleotide variants (SNVs) between generations. During development mutations accumulate in somatic cells so that an organism is a mosaic. However, variation within a tissue and between tissues has not been analysed. By reprogramming somatic cells into induced pluripotent stem cells (iPSCs), their genomes and the associated mutational history are captured. By sequencing the genomes of polyclonal and monoclonal somatic cells and derived iPSCs we have determined the mutation rates and show how the patterns change from a somatic lineage in vivo through to iPSCs. Somatic cells have a mutation rate of 14 SNVs per cell per generation while iPSCs exhibited a ten-fold lower rate. Analyses of mutational signatures suggested that deamination of methylated cytosine may be the major mutagenic source in vivo, whilst oxidative DNA damage becomes dominant in vitro. Our results provide insights for better understanding of mutational processes and lineage relationships between human somatic cells. Furthermore it provides a foundation for interpretation of elevated mutation rates and patterns in cancer.", "classifications": [ { "id": "Yusa", "label": "Group Yusa", "parent": "Eiraku", "type": "group" }, { "id": "Eiraku", "label": "Team Eiraku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Foad J.", "last_name": "Rouhani", "name": null }, { "creator_type": "author", "first_name": "Serena", "last_name": "Nik-Zainal", "name": null }, { "creator_type": "author", "first_name": "Arthur", "last_name": "Wuster", "name": null }, { "creator_type": "author", "first_name": "Yilong", "last_name": "Li", "name": null }, { "creator_type": "author", "first_name": "Nathalie", "last_name": "Conte", "name": null }, { "creator_type": "author", "first_name": "Hiroko", "last_name": "Koike-Yusa", "name": null }, { "creator_type": "author", "first_name": "Natsuhiko", "last_name": "Kumasaka", "name": null }, { "creator_type": "author", "first_name": "Ludovic", "last_name": "Vallier", "name": null }, { "creator_type": "author", "first_name": "Kosuke", "last_name": "Yusa", "name": null }, { "creator_type": "author", "first_name": "Allan", "last_name": "Bradley", "name": null } ], "identifiers": { "doi": { "normalized": "10.1371/journal.pgen.1005932" }, "pmcid": { "normalized": "PMC4824386" }, "pmid": { "normalized": "27054363" } }, "mesh": [ { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Cell Lineage", "descriptor_ui": "D019070", "major_topic": true }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Induced Pluripotent Stem Cells", "descriptor_ui": "D057026", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": true }, { "descriptor": "Polymorphism, Single Nucleotide", "descriptor_ui": "D020641", "major_topic": false }, { "descriptor": "Young Adult", "descriptor_ui": "D055815", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016 Apr", "date_precision": "unknown", "issue": "4", "normalized_date": null, "pages": "e1005932", "proceedings_title": null, "publisher": "", "title": "PLoS genetics", "volume": "12", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Mutational History of a Human Cell Lineage from Somatic to Induced Pluripotent Stem Cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Transient receptor potential canonical (TRPC) proteins form Ca(2+)-permeable cation channels activated upon stimulation of metabotropic receptors coupled to phospholipase C. Among the TRPC subfamily, TRPC3 and TRPC6 channels activated directly by diacylglycerol (DAG) play important roles in brain-derived neurotrophic factor (BDNF) signaling, promoting neuronal development and survival. In various disease models, BDNF restores neurologic deficits, but its therapeutic potential is limited by its poor pharmacokinetic profile. Elucidation of a framework for designing small molecules, which elicit BDNF-like activity via TRPC3 and TRPC6, establishes a solid basis to overcome this limitation. We discovered, through library screening, a group of piperazine-derived compounds that activate DAG-activated TRPC3/TRPC6/TRPC7 channels. The compounds [4-(5-chloro-2-methylphenyl)piperazin-1-yl](3-fluorophenyl)methanone (PPZ1) and 2-[4-(2,3-dimethylphenyl)piperazin-1-yl]-N-(2-ethoxyphenyl)acetamide (PPZ2) activated, in a dose-dependent manner, recombinant TRPC3/TRPC6/TRPC7 channels, but not other TRPCs, in human embryonic kidney cells. PPZ2 activated native TRPC6-like channels in smooth muscle cells isolated from rabbit portal vein. Also, PPZ2 evoked cation currents and Ca(2+) influx in rat cultured central neurons. Strikingly, both compounds induced BDNF-like neurite growth and neuroprotection, which were abolished by a knockdown or inhibition of TRPC3/TRPC6/TRPC7 in cultured neurons. Inhibitors of Ca(2+) signaling pathways, except calcineurin, impaired neurite outgrowth promotion induced by PPZ compounds. PPZ2 increased activation of the Ca(2+)-dependent transcription factor, cAMP response element-binding protein. These findings suggest that Ca(2+) signaling mediated by activation of DAG-activated TRPC channels underlies neurotrophic effects of PPZ compounds. Thus, piperazine-derived activators of DAG-activated TRPC channels provide important insights for future development of a new class of synthetic neurotrophic drugs.", "classifications": [ { "id": "Nishida", "label": "Group Nishida", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Seishiro", "last_name": "Sawamura", "name": null }, { "creator_type": "author", "first_name": "Masahiko", "last_name": "Hatano", "name": null }, { "creator_type": "author", "first_name": "Yoshinori", "last_name": "Takada", "name": null }, { "creator_type": "author", "first_name": "Kyosuke", "last_name": "Hino", "name": null }, { "creator_type": "author", "first_name": "Tetsuya", "last_name": "Kawamura", "name": null }, { "creator_type": "author", "first_name": "Jun", "last_name": "Tanikawa", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Nakagawa", "name": null }, { "creator_type": "author", "first_name": "Hideharu", "last_name": "Hase", "name": null }, { "creator_type": "author", "first_name": "Akito", "last_name": "Nakao", "name": null }, { "creator_type": "author", "first_name": "Mitsuru", "last_name": "Hirano", "name": null }, { "creator_type": "author", "first_name": "Rachapun", "last_name": "Rotrattanadumrong", "name": null }, { "creator_type": "author", "first_name": "Shigeki", "last_name": "Kiyonaka", "name": null }, { "creator_type": "author", "first_name": "Masayuki X.", "last_name": "Mori", "name": null }, { "creator_type": "author", "first_name": "Motohiro", "last_name": "Nishida", "name": null }, { "creator_type": "author", "first_name": "Yaopeng", "last_name": "Hu", "name": null }, { "creator_type": "author", "first_name": "Ryuji", "last_name": "Inoue", "name": null }, { "creator_type": "author", "first_name": "Ryu", "last_name": "Nagata", "name": null }, { "creator_type": "author", "first_name": "Yasuo", "last_name": "Mori", "name": null } ], "identifiers": { "doi": { "normalized": "10.1124/mol.115.102863" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "26733543" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Calcium Signaling", "descriptor_ui": "D020013", "major_topic": false }, { "descriptor": "Drug Evaluation, Preclinical", "descriptor_ui": "D004353", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "HEK293 Cells", "descriptor_ui": "D057809", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Membrane Potentials", "descriptor_ui": "D008564", "major_topic": false }, { "descriptor": "Myocytes, Smooth Muscle", "descriptor_ui": "D032389", "major_topic": false }, { "descriptor": "Nerve Growth Factors", "descriptor_ui": "D009414", "major_topic": false }, { "descriptor": "Piperazines", "descriptor_ui": "D010879", "major_topic": false }, { "descriptor": "Rabbits", "descriptor_ui": "D011817", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Rats, Wistar", "descriptor_ui": "D017208", "major_topic": false }, { "descriptor": "TRPC Cation Channels", "descriptor_ui": "D050052", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016 Mar", "date_precision": "unknown", "issue": "3", "normalized_date": null, "pages": "348-363", "proceedings_title": null, "publisher": "", "title": "Molecular pharmacology", "volume": "89", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Screening of Transient Receptor Potential Canonical Channel Activators Identifies Novel Neurotrophic Piperazine Compounds.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Raman scattering microscopy provides information about the distribution and chemical state of molecules in live cells without any labeling or modification. In recent years, the imaging speed of Raman microscopy has improved greatly owing to the development of instruments that can perform parallel acquisition of Raman spectra from multiple points. In this article, we review recent advances in high-speed hyperspectral Raman imaging and its application to observe various biological processes such as cell mitosis, apoptosis and cell differentiation. Furthermore, we discuss the recent progress in Raman tags for the specific observation of bioactive small molecules in complex biological systems, including the development of organelle-specific probes, imaging of lipid rafts in an artificial monolayer membrane and application as a structure-sensitive tag.", "classifications": [ { "id": "Fujita", "label": "Group Fujita", "parent": "Fujita", "type": "group" }, { "id": "Sodeoka", "label": "Group Sodeoka", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Jun", "last_name": "Ando", "name": null }, { "creator_type": "author", "first_name": "Almar F.", "last_name": "Palonpon", "name": null }, { "creator_type": "author", "first_name": "Mikiko", "last_name": "Sodeoka", "name": null }, { "creator_type": "author", "first_name": "Katsumasa", "last_name": "Fujita", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.cbpa.2016.04.005" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "27107216" } }, "mesh": [ { "descriptor": "HeLa Cells", "descriptor_ui": "D006367", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Membrane Microdomains", "descriptor_ui": "D021962", "major_topic": false }, { "descriptor": "Molecular Imaging", "descriptor_ui": "D057054", "major_topic": false }, { "descriptor": "Spectrum Analysis, Raman", "descriptor_ui": "D013059", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016 Aug", "date_precision": "unknown", "issue": "", "normalized_date": null, "pages": "16-24", "proceedings_title": null, "publisher": "", "title": "Current opinion in chemical biology", "volume": "33", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "High-speed Raman imaging of cellular processes.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "A decrease in system size can induce qualitatively different behavior compared to the macroscopic behavior of the corresponding large-size system. The mechanisms of this transition, which is known as the small-size transition, can be attributed to either a relative increase in the noise intensity or to the discreteness of the state space due to the small system size. The former mechanism has been intensively investigated using several toy and realistic models. However, the latter has rarely been analyzed and is sometimes confused with the former, because a toy model that extracts the essence of the discreteness-induced transition mechanism is lacking. In this work, we propose a one- and three-body reaction system as a minimal model of the discreteness-induced transition and derive the conditions under which this transition occurs in more complex systems. This work enriches our understanding of the influence of small system size on system behavior.", "classifications": [ { "id": "Kobayashi", "label": "Group Kobayashi", "parent": "Wakamoto", "type": "group" }, { "id": "Wakamoto", "label": "Team Wakamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yohei", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Sughiyama", "name": null }, { "creator_type": "author", "first_name": "Kunihiko", "last_name": "Kaneko", "name": null }, { "creator_type": "author", "first_name": "Tetsuya J.", "last_name": "Kobayashi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1103/physreve.94.022140" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "27627279" } }, "mesh": [], "publication": { "conference_name": null, "date": "2016 Aug", "date_precision": "unknown", "issue": "2-1", "normalized_date": null, "pages": "022140", "proceedings_title": null, "publisher": "", "title": "Physical review. E", "volume": "94", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Discreteness-induced transitions in multibody reaction systems.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Networks of biofilaments are essential for the formation of cellular structures that support various biological functions. For the most part, previous studies have investigated the collective dynamics of rodlike biofilaments; however, the shapes of the actual subcellular components are often more elaborate. In this study, we considered an active object composed of two active filaments, which represents the progression from rodlike biofilaments to complex-shaped biofilaments. Specifically, we numerically assessed the collective behaviors of these active objects in two dimensions and observed several types of dynamics, depending on the density and the angle of the two filaments as shape parameters of the object. Among the observed collective dynamics, a moving density band that we named a \"moving smectic\" is introduced here for the first time. By analyzing the trajectories of individual objects and the interactions among them, this study demonstrated how interactions among active biofilaments with complex shapes could produce collective dynamics in a nontrivial manner.", "classifications": [ { "id": "Ishihara", "label": "Group Ishihara", "parent": "Sawai", "type": "group" }, { "id": "Sawai", "label": "Team Sawai", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Hironobu", "last_name": "Nogucci", "name": null }, { "creator_type": "author", "first_name": "Shuji", "last_name": "Ishihara", "name": null } ], "identifiers": { "doi": { "normalized": "10.1103/physreve.93.052406" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "27300923" } }, "mesh": [ { "descriptor": "Cytoskeleton", "descriptor_ui": "D003599", "major_topic": false }, { "descriptor": "Models, Biological", "descriptor_ui": "D008954", "major_topic": true } ], "publication": { "conference_name": null, "date": "2016 May", "date_precision": "unknown", "issue": "5", "normalized_date": null, "pages": "052406", "proceedings_title": null, "publisher": "", "title": "Physical review. E", "volume": "93", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Collective dynamics of active filament complexes.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Cry j1 is the major peptide allergen of Japanese cedar (Sugi), Cryptomeria japonica. Since some allergens disrupt epidermal permeability barrier homeostasis, we hypothesized that Cry j1 might have a similar effect. Intracellular calcium level in cultured human keratinocytes was measured with a ratiometric fluorescent probe, Fura-2 AM. Application of Cry j1 significantly increased the intracellular calcium level of keratinocytes, and this increase was inhibited by trypsin inhibitor or a protease-activated receptor 2 (PAR-2) antagonist. We found that Cry j1 itself did not show protease activity, but application of Cry j1 to cultured keratinocytes induced a rapid (within 30 s) and transient increase of protease activity in the medium. This transient increase was blocked by trypsin inhibitor or PAR-2 antagonist. The effect of Cry j1 on transepidermal water loss (TEWL) of cultured human skin was measured in the presence and absence of a trypsin inhibitor and PAR-2 antagonist. Cry j1 significantly impaired the barrier function of human skin ex vivo, and this action was blocked by co-application of trypsin inhibitor or PAR-2 antagonist. Our results suggested that interaction of Cry j1 with epidermal keratinocytes leads to the activation of PAR-2, which induces elevation of intracellular calcium and disruption of barrier function. Blocking the interaction of Cry j1 with epidermal keratinocytes might ameliorate allergic reaction and prevent disruption of epidermal permeability barrier homeostasis.", "classifications": [ { "id": "Nagayama", "label": "Group Nagayama", "parent": "Fujiwara", "type": "group" }, { "id": "Fujiwara", "label": "Team Fujiwara", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Junichi", "last_name": "Kumamoto", "name": null }, { "creator_type": "author", "first_name": "Moe", "last_name": "Tsutsumi", "name": null }, { "creator_type": "author", "first_name": "Makiko", "last_name": "Goto", "name": null }, { "creator_type": "author", "first_name": "Masaharu", "last_name": "Nagayama", "name": null }, { "creator_type": "author", "first_name": "Mitsuhiro", "last_name": "Denda", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/s00403-015-1602-y" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "26498292" } }, "mesh": [ { "descriptor": "Allergens", "descriptor_ui": "D000485", "major_topic": false }, { "descriptor": "Antigens, Plant", "descriptor_ui": "D052179", "major_topic": false }, { "descriptor": "Calcium", "descriptor_ui": "D002118", "major_topic": false }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Cryptomeria", "descriptor_ui": "D032485", "major_topic": false }, { "descriptor": "Epidermis", "descriptor_ui": "D004817", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Hypersensitivity", "descriptor_ui": "D006967", "major_topic": false }, { "descriptor": "Keratinocytes", "descriptor_ui": "D015603", "major_topic": false }, { "descriptor": "Organ Culture Techniques", "descriptor_ui": "D009924", "major_topic": false }, { "descriptor": "Peptide Hydrolases", "descriptor_ui": "D010447", "major_topic": false }, { "descriptor": "Plant Proteins", "descriptor_ui": "D010940", "major_topic": false }, { "descriptor": "Pollen", "descriptor_ui": "D011058", "major_topic": false }, { "descriptor": "Protease Inhibitors", "descriptor_ui": "D011480", "major_topic": false }, { "descriptor": "Receptor, PAR-2", "descriptor_ui": "D044464", "major_topic": false }, { "descriptor": "Tight Junctions", "descriptor_ui": "D019108", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016 Jan", "date_precision": "unknown", "issue": "1", "normalized_date": null, "pages": "49-54", "proceedings_title": null, "publisher": "", "title": "Archives of dermatological research", "volume": "308", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Japanese Cedar (Cryptomeria japonica) pollen allergen induces elevation of intracellular calcium in human keratinocytes and impairs epidermal barrier function of human skin ex vivo.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "In the social amoeba Dictyostelium discoideum, travelling waves of extracellular cyclic adenosine monophosphate (cAMP) self-organize in cell populations and direct aggregation of individual cells to form multicellular fruiting bodies. In contrast to the large body of studies that addressed how movement of cells is determined by spatial and temporal cues encoded in the dynamic cAMP gradients, how cell mechanics affect the formation of a self-generated chemoattractant field has received less attention. Here, we show, by live cell imaging analysis, that the periodicity of the synchronized cAMP waves increases in cells treated with the actin inhibitor latrunculin. Detail analysis of the extracellular cAMP-induced transients of cytosolic cAMP (cAMP relay response) in well-isolated cells demonstrated that their amplitude and duration were markedly reduced in latrunculin-treated cells. Similarly, in cells strongly adhered to a poly-l-lysine-coated surface, the response was suppressed, and the periodicity of the population-level oscillations was markedly lengthened. Our results suggest that cortical F-actin is dispensable for the basic low amplitude relay response but essential for its full amplification and that this enhanced response is necessary to establish high-frequency signalling centres. The observed F-actin dependence may prevent aggregation centres from establishing in microenvironments that are incompatible with cell migration.", "classifications": [ { "id": "Sawai", "label": "Group Sawai", "parent": "Sawai", "type": "group" }, { "id": "Sawai", "label": "Team Sawai", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Fumihito", "last_name": "Fukujin", "name": null }, { "creator_type": "author", "first_name": "Akihiko", "last_name": "Nakajima", "name": null }, { "creator_type": "author", "first_name": "Nao", "last_name": "Shimada", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Sawai", "name": null } ], "identifiers": { "doi": { "normalized": "10.1098/rsif.2016.0233" }, "pmcid": { "normalized": "PMC4938087" }, "pmid": { "normalized": "27358278" } }, "mesh": [ { "descriptor": "Actins", "descriptor_ui": "D000199", "major_topic": false }, { "descriptor": "Chemotactic Factors", "descriptor_ui": "D002630", "major_topic": false }, { "descriptor": "Cyclic AMP", "descriptor_ui": "D000242", "major_topic": false }, { "descriptor": "Dictyostelium", "descriptor_ui": "D004023", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016 Jun", "date_precision": "unknown", "issue": "119", "normalized_date": null, "pages": "20160233", "proceedings_title": null, "publisher": "", "title": "Journal of the Royal Society, Interface", "volume": "13", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Self-organization of chemoattractant waves in Dictyostelium depends on F-actin and cell-substrate adhesion.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: Jumonji domain-containing 2B, JMJD2B, has been shown to play an important role in the pathogenesis of lung cancer cells. However, the significance of JMJD2B in patients with lung cancer remains to be elucidated. PATIENTS AND METHODS: Seventy-eight patients with resected adenocarcinoma, whose data regarding oncogenic drivers in lung cancer were available, were included in the study. Immunohistochemical analysis was performed with a specific antibody for JMJD2B to investigate JMJD2B expression and the significance of JMJD2B expression in survival after surgery was evaluated. RESULTS: Among the 78 patients, 50 (64%) exhibited JMJD2B immunopositivity. The overall survival (OS) of the 50 JMJD2B-positive patients after surgery was significantly inferior to that of the JMJD2B-negative patients (five-year survival=56.7% vs. 92.6%; log-rank: p=0.01). Multivariate analysis showed that JMJD2B positivity was an independent prognostic factor. CONCLUSION: JMJD2B may be a novel prognostic factor for resected lung adenocarcinoma.", "classifications": [ { "id": "Hamamoto", "label": "Group Hamamoto", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Gouji", "last_name": "Toyokawa", "name": null }, { "creator_type": "author", "first_name": "Kenichi", "last_name": "Taguchi", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Edagawa", "name": null }, { "creator_type": "author", "first_name": "Shinichiro", "last_name": "Shimamatsu", "name": null }, { "creator_type": "author", "first_name": "Ryo", "last_name": "Toyozawa", "name": null }, { "creator_type": "author", "first_name": "Kaname", "last_name": "Nosaki", "name": null }, { "creator_type": "author", "first_name": "Fumihiko", "last_name": "Hirai", "name": null }, { "creator_type": "author", "first_name": "Masafumi", "last_name": "Yamaguchi", "name": null }, { "creator_type": "author", "first_name": "Mototsugu", "last_name": "Shimokawa", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Seto", "name": null }, { "creator_type": "author", "first_name": "Mitsuhiro", "last_name": "Takenoyama", "name": null }, { "creator_type": "author", "first_name": "Ryuji", "last_name": "Hamamoto", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Sugio", "name": null }, { "creator_type": "author", "first_name": "Yukito", "last_name": "Ichinose", "name": null } ], "identifiers": { "doi": { "normalized": "10.21873/anticanres.11046" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "27630338" } }, "mesh": [ { "descriptor": "Adenocarcinoma", "descriptor_ui": "D000230", "major_topic": false }, { "descriptor": "Adenocarcinoma of Lung", "descriptor_ui": "D000077192", "major_topic": false }, { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Aged, 80 and over", "descriptor_ui": "D000369", "major_topic": false }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Cell Proliferation", "descriptor_ui": "D049109", "major_topic": false }, { "descriptor": "Disease-Free Survival", "descriptor_ui": "D018572", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Gene Expression Regulation, Neoplastic", "descriptor_ui": "D015972", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Jumonji Domain-Containing Histone Demethylases", "descriptor_ui": "D056484", "major_topic": false }, { "descriptor": "Kaplan-Meier Estimate", "descriptor_ui": "D053208", "major_topic": false }, { "descriptor": "Lung Neoplasms", "descriptor_ui": "D008175", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Prognosis", "descriptor_ui": "D011379", "major_topic": true } ], "publication": { "conference_name": null, "date": "2016 Sep", "date_precision": "unknown", "issue": "9", "normalized_date": null, "pages": "4841-4846", "proceedings_title": null, "publisher": "", "title": "Anticancer research", "volume": "36", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "The Prognostic Impact of Jumonji Domain-containing 2B in Patients with Resected Lung Adenocarcinoma.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND AND AIMS: Phenotypic variation in floral morphologies contributes to speciation by testing various morphologies that might have higher adaptivity, leading eventually to phylogenetic diversity. Species diversity has been recognized, however, by modal morphologies where the variation is averaged out, so little is known about the relationship between the variation and the diversity. METHODS: We analysed quantitatively the intraspecific variation of the organ numbers within flowers of Ranunculaceae, a family which branched near the monocot-eudicot separation, and the numbers of flowers within the capitula of Asteraceae, one of the most diverse families of eudicots. We used four elementary statistical quantities: mean, standard deviation (s.d.), degree of symmetry (skewness) and steepness (kurtosis). KEY RESULTS: While these four quantities vary among populations, we found a common relationship between s.d. and the mean number of petals and sepals in Ranunculaceae and number of flowers per capitulum in Asteraceae. The s.d. is equal to the square root of the difference between the mean and specific number, showing robustness: for example, 3 in Ficaria sepals, 5 in Ranunculus petals and Anemone tepals, and 13 in Farfugium ray florets. This square-root relationship was not applicable to Eranthis petals which show little correlation between the s.d. and mean, and the stamens and carpels of Ranunculaceae whose s.d. is proportional to the mean. The specific values found in the square-root relationship provide a novel way to find the species-representative phenotype among varied morphologies. CONCLUSIONS: The representative phenotype is, in most cases, unique to the species or genus level, despite intraspecific differences of average phenotype among populations. The type of variation shown by the statistical quantities indicates not only the robustness of the morphologies but also how flowering plants changed during evolution among representative phenotypes that eventually led to phylogenetic diversification.", "classifications": [ { "id": "Fujimoto", "label": "Group Fujimoto", "parent": "Ueda", "type": "group" }, { "id": "Ueda", "label": "Team Ueda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Miho S.", "last_name": "Kitazawa", "name": null }, { "creator_type": "author", "first_name": "Koichi", "last_name": "Fujimoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1093/aob/mcw034" }, "pmcid": { "normalized": "PMC4845808" }, "pmid": { "normalized": "27052344" } }, "mesh": [ { "descriptor": "Asteraceae", "descriptor_ui": "D019659", "major_topic": false }, { "descriptor": "Data Interpretation, Statistical", "descriptor_ui": "D003627", "major_topic": false }, { "descriptor": "Flowers", "descriptor_ui": "D035264", "major_topic": false }, { "descriptor": "Phenotype", "descriptor_ui": "D010641", "major_topic": false }, { "descriptor": "Ranunculaceae", "descriptor_ui": "D029626", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016 Apr", "date_precision": "unknown", "issue": "5", "normalized_date": null, "pages": "925-935", "proceedings_title": null, "publisher": "", "title": "Annals of botany", "volume": "117", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Relationship between the species-representative phenotype and intraspecific variation in Ranunculaceae floral organ and Asteraceae flower numbers.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Signal transduction processes the information of various cellular functions, including cell proliferation, differentiation, and death. The information for controlling cell fate is transmitted by concentrations of cellular signaling molecules. However, how much information is transmitted in signaling pathways has thus far not been investigated. Shannon's information theory paves the way to quantitatively analyze information transmission in signaling pathways. The theory has recently been applied to signal transduction, and mutual information of signal transduction has been determined to be a measure of information transmission. We review this work and provide an overview of how signal transduction transmits informational input and exerts biological output.", "classifications": [ { "id": "Kuroda", "label": "Group Kuroda", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Shinsuke", "last_name": "Uda", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Kuroda", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.semcdb.2015.12.011" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "26710655" } }, "mesh": [ { "descriptor": "Algorithms", "descriptor_ui": "D000465", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Computational Biology", "descriptor_ui": "D019295", "major_topic": false }, { "descriptor": "Entropy", "descriptor_ui": "D019277", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Information Theory", "descriptor_ui": "D007257", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": true }, { "descriptor": "Uncertainty", "descriptor_ui": "D035501", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016 Mar", "date_precision": "unknown", "issue": "", "normalized_date": null, "pages": "24-31", "proceedings_title": null, "publisher": "", "title": "Seminars in cell & developmental biology", "volume": "51", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Analysis of cellular signal transduction from an information theoretic approach.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Antisense RNA has emerged as a crucial regulator of opposite-strand protein-coding genes in the long noncoding RNA (lncRNA) category, but little is known about their dynamics and decay process in the context of a stress response. Antisense transcripts from the fission yeast fbp1 locus (fbp1-as) are expressed in glucose-rich conditions and anticorrelated with transcription of metabolic stress-induced lncRNA (mlonRNA) and mRNA on the sense strand during glucose starvation. Here, we investigate the localization and decay of antisense RNAs at fbp1 and other loci, and propose a model to explain the rapid switch between antisense and sense mlonRNA/mRNA transcription triggered by glucose starvation. We show that fbp1-as shares many features with mRNAs, such as a 5'-cap and poly(A)-tail, and that its decay partially depends upon Rrp6, a cofactor of the nuclear exosome complex involved in 3'-5' degradation of RNA. Fluorescence in situ hybridization and polysome fractionation show that the majority of remaining fbp1-as localizes to the cytoplasm and binds to polyribosomes in glucose-rich conditions. Furthermore, fbp1-as and antisense RNA at other stress-responsive loci are promptly degraded via the cotranslational nonsense-mediated decay (NMD) pathway. These results suggest NMD may potentiate the swift disappearance of antisense RNAs in response to cellular stress.", "classifications": [ { "id": "Sawai", "label": "Group Sawai", "parent": "Sawai", "type": "group" }, { "id": "Sawai", "label": "Team Sawai", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Atsuko", "last_name": "Miki", "name": null }, { "creator_type": "author", "first_name": "Josephine", "last_name": "Galipon", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Sawai", "name": null }, { "creator_type": "author", "first_name": "Toshifumi", "last_name": "Inada", "name": null }, { "creator_type": "author", "first_name": "Kunihiro", "last_name": "Ohta", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/gtc.12443" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "27723196" } }, "mesh": [ { "descriptor": "Cytoplasm", "descriptor_ui": "D003593", "major_topic": false }, { "descriptor": "Gene Expression Regulation, Fungal", "descriptor_ui": "D015966", "major_topic": true }, { "descriptor": "Genes, Fungal", "descriptor_ui": "D005800", "major_topic": false }, { "descriptor": "Glucose", "descriptor_ui": "D005947", "major_topic": false }, { "descriptor": "Ribosomes", "descriptor_ui": "D012270", "major_topic": false }, { "descriptor": "RNA Stability", "descriptor_ui": "D020871", "major_topic": false }, { "descriptor": "RNA, Antisense", "descriptor_ui": "D016372", "major_topic": false }, { "descriptor": "RNA, Fungal", "descriptor_ui": "D012331", "major_topic": false }, { "descriptor": "RNA, Long Noncoding", "descriptor_ui": "D062085", "major_topic": false }, { "descriptor": "Schizosaccharomyces", "descriptor_ui": "D012568", "major_topic": false }, { "descriptor": "Stress, Physiological", "descriptor_ui": "D013312", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016 Dec", "date_precision": "unknown", "issue": "12", "normalized_date": null, "pages": "1276-1289", "proceedings_title": null, "publisher": "", "title": "Genes to cells : devoted to molecular & cellular mechanisms", "volume": "21", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "RNA decay systems enhance reciprocal switching of sense and antisense transcripts in response to glucose starvation.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The recent discovery of significant hydropersulfide (RSSH) levels in mammalian tissues, fluids and cells has led to numerous questions regarding their possible physiological function. Cysteine hydropersulfides have been found in free cysteine, small molecule peptides as well as in proteins. Based on their chemical properties and likely cellular conditions associated with their biosynthesis, it has been proposed that they can serve a protective function. That is, hydropersulfide formation on critical thiols may protect them from irreversible oxidative or electrophilic inactivation. As a prelude to understanding the possible roles and functions of hydropersulfides in biological systems, this study utilizes primarily chemical experiments to delineate the possible mechanistic chemistry associated with cellular protection. Thus, the ability of hydropersulfides to protect against irreversible electrophilic and oxidative modification was examined. The results herein indicate that hydropersulfides are very reactive towards oxidants and electrophiles and are modified readily. However, reduction of these oxidized/modified species is facile generating the corresponding thiol, consistent with the idea that hydropersulfides can serve a protective function for thiol proteins.", "classifications": [ { "id": "Akaike", "label": "Group Akaike", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Robert", "last_name": "Millikin", "name": null }, { "creator_type": "author", "first_name": "Christopher L.", "last_name": "Bianco", "name": null }, { "creator_type": "author", "first_name": "Corey", "last_name": "White", "name": null }, { "creator_type": "author", "first_name": "Simran S.", "last_name": "Saund", "name": null }, { "creator_type": "author", "first_name": "Stephanie", "last_name": "Henriquez", "name": null }, { "creator_type": "author", "first_name": "Victor", "last_name": "Sosa", "name": null }, { "creator_type": "author", "first_name": "Takaaki", "last_name": "Akaike", "name": null }, { "creator_type": "author", "first_name": "Yoshito", "last_name": "Kumagai", "name": null }, { "creator_type": "author", "first_name": "Shuhei", "last_name": "Soeda", "name": null }, { "creator_type": "author", "first_name": "John P.", "last_name": "Toscano", "name": null }, { "creator_type": "author", "first_name": "Joseph", "last_name": "Lin", "name": null }, { "creator_type": "author", "first_name": "Jon M.", "last_name": "Fukuto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.freeradbiomed.2016.05.013" }, "pmcid": { "normalized": "PMC4996688" }, "pmid": { "normalized": "27242269" } }, "mesh": [ { "descriptor": "Cysteine", "descriptor_ui": "D003545", "major_topic": false }, { "descriptor": "Oxidation-Reduction", "descriptor_ui": "D010084", "major_topic": false }, { "descriptor": "Oxidative Stress", "descriptor_ui": "D018384", "major_topic": true }, { "descriptor": "Proteins", "descriptor_ui": "D011506", "major_topic": false }, { "descriptor": "Reactive Oxygen Species", "descriptor_ui": "D017382", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Sulfhydryl Compounds", "descriptor_ui": "D013438", "major_topic": false }, { "descriptor": "Sulfides", "descriptor_ui": "D013440", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016 Aug", "date_precision": "unknown", "issue": "", "normalized_date": null, "pages": "136-147", "proceedings_title": null, "publisher": "", "title": "Free radical biology & medicine", "volume": "97", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "The chemical biology of protein hydropersulfides: Studies of a possible protective function of biological hydropersulfide generation.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: Multiple studies have investigated sampling adequacy of endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) for pancreatic neuroendocrine neoplasms (pNENs). However, none have described the diagnostic performance of EUS-FNA for pNENs, or the influencing factors. The aim of this study was to evaluate the diagnostic accuracy of EUS-FNA, with post-operative pathological diagnosis as the gold standard, and factors predictive of inadequate EUS sampling. METHODS: From 1998 to 2014, a total of 698 patients underwent pancreatic resection and 1455 patients underwent EUS-FNA sampling for pancreatic lesions. A total of 410 cases underwent both surgical resection and preceding EUS-FNA. Of these, 60 cases (49 true pNEN, nine non-diagnostic, two misdiagnoses) were included. We studied diagnostic performance of EUS-FNA and factors that were associated with failed diagnosis. RESULTS: Of the 60 cases, EUS-FNA yield was 49 true-positive cases, two misdiagnoses, and nine non-diagnostic cases (including six suggestive cases). Sensitivity, specificity, and accuracy were 84.5, 99.4, and 97.3 %, respectively; including the six suggestive cases, diagnostic values were 94.8 % sensitivity (55/58), 99.4 % specificity (350/352), and 98.7 % accuracy (405/410). In multivariate analysis, sampling adequacy rates were significantly lower when lesions were located in the pancreatic head [odds ratio (OR) = 10.0] and in tumor-rich stromal fibrosis (OR = 10.45). Tumor size, needle type, tumor grading, presence of cystic component, and time period were not significant factors. CONCLUSIONS: EUS-FNA offers high accuracy for pNEN. However, location of the tumor in the pancreatic head and presence of rich stromal fibrosis negatively impacts sampling adequacy.", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Susumu", "last_name": "Hijioka", "name": null }, { "creator_type": "author", "first_name": "Kazuo", "last_name": "Hara", "name": null }, { "creator_type": "author", "first_name": "Nobumasa", "last_name": "Mizuno", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Imaoka", "name": null }, { "creator_type": "author", "first_name": "Vikram", "last_name": "Bhatia", "name": null }, { "creator_type": "author", "first_name": "Mohamed A.", "last_name": "Mekky", "name": null }, { "creator_type": "author", "first_name": "Kenichi", "last_name": "Yoshimura", "name": null }, { "creator_type": "author", "first_name": "Tsukasa", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Nozomi", "last_name": "Okuno", "name": null }, { "creator_type": "author", "first_name": "Nobuhiro", "last_name": "Hieda", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Tajika", "name": null }, { "creator_type": "author", "first_name": "Tsutomu", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Ishihara", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null }, { "creator_type": "author", "first_name": "Yasuhiro", "last_name": "Shimizu", "name": null }, { "creator_type": "author", "first_name": "Yasumasa", "last_name": "Niwa", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Yamao", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/s00535-016-1164-6" }, "pmcid": { "normalized": "PMC4990623" }, "pmid": { "normalized": "26768605" } }, "mesh": [ { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Endoscopic Ultrasound-Guided Fine Needle Aspiration", "descriptor_ui": "D061765", "major_topic": true }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Neuroendocrine Tumors", "descriptor_ui": "D018358", "major_topic": false }, { "descriptor": "Pancreatic Neoplasms", "descriptor_ui": "D010190", "major_topic": false }, { "descriptor": "Retrospective Studies", "descriptor_ui": "D012189", "major_topic": false }, { "descriptor": "Sensitivity and Specificity", "descriptor_ui": "D012680", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016 Sep", "date_precision": "unknown", "issue": "9", "normalized_date": null, "pages": "923-930", "proceedings_title": null, "publisher": "", "title": "Journal of gastroenterology", "volume": "51", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Diagnostic performance and factors influencing the accuracy of EUS-FNA of pancreatic neuroendocrine neoplasms.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "", "classifications": [ { "id": "Nagayama", "label": "Group Nagayama", "parent": "Fujiwara", "type": "group" }, { "id": "Fujiwara", "label": "Team Fujiwara", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Kentaro", "last_name": "Takei", "name": null }, { "creator_type": "author", "first_name": "Sumiko", "last_name": "Denda", "name": null }, { "creator_type": "author", "first_name": "Masaharu", "last_name": "Nagayama", "name": null }, { "creator_type": "author", "first_name": "Mitsuhiro", "last_name": "Denda", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/exd.12928" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "26738614" } }, "mesh": [ { "descriptor": "Adenosine Triphosphatases", "descriptor_ui": "D000251", "major_topic": false }, { "descriptor": "Adenosine Triphosphate", "descriptor_ui": "D000255", "major_topic": false }, { "descriptor": "Calcium", "descriptor_ui": "D002118", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "Cell Proliferation", "descriptor_ui": "D049109", "major_topic": false }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Keratinocytes", "descriptor_ui": "D015603", "major_topic": false }, { "descriptor": "Neoplasm Proteins", "descriptor_ui": "D009363", "major_topic": false }, { "descriptor": "ORAI1 Protein", "descriptor_ui": "D000071740", "major_topic": false }, { "descriptor": "Stromal Interaction Molecule 1", "descriptor_ui": "D000071737", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016 Apr", "date_precision": "unknown", "issue": "4", "normalized_date": null, "pages": "323-325", "proceedings_title": null, "publisher": "", "title": "Experimental dermatology", "volume": "25", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Role of STIM1-Orai1 system in intra-cellular calcium elevation induced by ATP in cultured human keratinocytes.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "CITED2 (Cbp/p300-interacting transactivator, with Glu/Asp-rich carboxy-terminal domain, 2) is a member of the CITED family and is involved in various cellular functions during development and differentiation. Mounting evidence suggests the importance of CITED in the progression of human malignancies, but the significance of CITED2 protein has not yet been examined in breast carcinoma. Therefore, in the present study, we examined the clinical significance and the biological functions of CITED2 in breast carcinoma by immunohistochemistry and in vitro study. CITED2 immunoreactivity was detected in breast carcinoma tissues, and it was significantly higher compared to those in morphologically normal mammary glands. CITED2 immunoreactivity was significantly associated with stage, pathological T factor, lymph node metastasis, histological grade, HER2 and Ki-67, and inversely correlated with estrogen receptor. Moreover, the immunohistochemical CITED2 status was significantly associated with increased incidence of recurrence and breast cancer-specific death of the breast cancer patients, and multivariate analyses demonstrated CITED2 status as an independent worse prognostic factor for disease-free and breast cancer-specific survival. Subsequent in vitro experiments showed that CITED2 expression significantly increased proliferation activity and migration property in MCF-7and S KBR-3 breast carcinoma cells. Moreover, CITED2 caused chemoresistance to epirubicin and 5-fluorouracil, but not paclitaxel, in these cells, and it inhibited p53 accumulation after 5-fluorouracil treatment in MCF-7 cells. These results suggest that CITED2 plays important roles in the progression and chemoresistance of breast carcinoma and that CITED2 status is a potent prognostic factor in breast cancer patients.", "classifications": [ { "id": "Suzuki", "label": "Group Suzuki", "parent": "Takekawa", "type": "group" }, { "id": "Takekawa", "label": "Team Takekawa", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Minemura", "name": null }, { "creator_type": "author", "first_name": "Kiyoshi", "last_name": "Takagi", "name": null }, { "creator_type": "author", "first_name": "Ai", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Hikaru", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Yasuhiro", "last_name": "Miki", "name": null }, { "creator_type": "author", "first_name": "Yukiko", "last_name": "Shibahara", "name": null }, { "creator_type": "author", "first_name": "Mika", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Takanori", "last_name": "Ishida", "name": null }, { "creator_type": "author", "first_name": "Hironobu", "last_name": "Sasano", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Suzuki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/cas.13081" }, "pmcid": { "normalized": "PMC5198946" }, "pmid": { "normalized": "27627783" } }, "mesh": [ { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Aged, 80 and over", "descriptor_ui": "D000369", "major_topic": false }, { "descriptor": "Biomarkers, Tumor", "descriptor_ui": "D014408", "major_topic": false }, { "descriptor": "Breast Neoplasms", "descriptor_ui": "D001943", "major_topic": false }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Cell Movement", "descriptor_ui": "D002465", "major_topic": false }, { "descriptor": "Cell Proliferation", "descriptor_ui": "D049109", "major_topic": false }, { "descriptor": "Disease-Free Survival", "descriptor_ui": "D018572", "major_topic": false }, { "descriptor": "Drug Resistance, Neoplasm", "descriptor_ui": "D019008", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Fluorouracil", "descriptor_ui": "D005472", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Immunohistochemistry", "descriptor_ui": "D007150", "major_topic": false }, { "descriptor": "MCF-7 Cells", "descriptor_ui": "D061986", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Neoplasm Grading", "descriptor_ui": "D060787", "major_topic": false }, { "descriptor": "Neoplasm Staging", "descriptor_ui": "D009367", "major_topic": false }, { "descriptor": "Prognosis", "descriptor_ui": "D011379", "major_topic": false }, { "descriptor": "Proportional Hazards Models", "descriptor_ui": "D016016", "major_topic": false }, { "descriptor": "Protein Biosynthesis", "descriptor_ui": "D014176", "major_topic": false }, { "descriptor": "Repressor Proteins", "descriptor_ui": "D012097", "major_topic": false }, { "descriptor": "Trans-Activators", "descriptor_ui": "D015534", "major_topic": false }, { "descriptor": "Tumor Suppressor Protein p53", "descriptor_ui": "D016159", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016 Dec", "date_precision": "unknown", "issue": "12", "normalized_date": null, "pages": "1898-1908", "proceedings_title": null, "publisher": "", "title": "Cancer science", "volume": "107", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "CITED2 in breast carcinoma as a potent prognostic predictor associated with proliferation, migration and chemoresistance.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "We report molecular dynamics simulations of the segregation of two overlapping polymers motivated by chromosome segregation in biological cells. We investigate the relationship between polymer shapes and segregation dynamics and show that elongation and compaction make entangled polymers segregate rapidly. This result suggests that eukaryotic chromosomes take such a characteristic rod-shaped structure, which is induced by condensins, to achieve rapid segregation.", "classifications": [ { "id": "Mochizuki", "label": "Group Mochizuki", "parent": "Eiraku", "type": "group" }, { "id": "Eiraku", "label": "Team Eiraku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yuji", "last_name": "Sakai", "name": null }, { "creator_type": "author", "first_name": "Masashi", "last_name": "Tachikawa", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Mochizuki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1103/physreve.94.042403" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "27841590" } }, "mesh": [ { "descriptor": "Chromosome Segregation", "descriptor_ui": "D020090", "major_topic": true }, { "descriptor": "Eukaryota", "descriptor_ui": "D056890", "major_topic": false }, { "descriptor": "Molecular Dynamics Simulation", "descriptor_ui": "D056004", "major_topic": true }, { "descriptor": "Polymers", "descriptor_ui": "D011108", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016 Oct", "date_precision": "unknown", "issue": "4-1", "normalized_date": null, "pages": "042403", "proceedings_title": null, "publisher": "", "title": "Physical review. E", "volume": "94", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Controlling segregation speed of entangled polymers by the shapes: A simple model for eukaryotic chromosome segregation.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Structural analyses of proteins under macromolecular crowding inside human cultured cells by in-cell NMR spectroscopy are crucial not only for explicit understanding of their cellular functions but also for applications in medical and pharmaceutical sciences. In-cell NMR experiments using human cultured cells however suffer from low sensitivity, thus pseudocontact shifts from protein-tagged paramagnetic lanthanoid ions, analysed using sensitive heteronuclear two-dimensional correlation NMR spectra, offer huge potential advantage in obtaining structural information over conventional NOE-based approaches. We synthesised a new lanthanoid-chelating tag (M8-CAM-I), in which the eight-fold, stereospecifically methylated DOTA (M8) scaffold was retained, while a stable carbamidemethyl (CAM) group was introduced as the functional group connecting to proteins. M8-CAM-I successfully fulfilled the requirements for in-cell NMR: high-affinity to lanthanoid, low cytotoxicity and the stability under reducing condition inside cells. Large PCSs for backbone N-H resonances observed for M8-CAM-tagged human ubiquitin mutant proteins, which were introduced into HeLa cells by electroporation, demonstrated that this approach readily provides the useful information enabling the determination of protein structures, relative orientations of domains and protein complexes within human cultured cells.", "classifications": [ { "id": "Sodeoka", "label": "Group Sodeoka", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yuya", "last_name": "Hikone", "name": null }, { "creator_type": "author", "first_name": "Go", "last_name": "Hirai", "name": null }, { "creator_type": "author", "first_name": "Masaki", "last_name": "Mishima", "name": null }, { "creator_type": "author", "first_name": "Kohsuke", "last_name": "Inomata", "name": null }, { "creator_type": "author", "first_name": "Teppei", "last_name": "Ikeya", "name": null }, { "creator_type": "author", "first_name": "Souichiro", "last_name": "Arai", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Shirakawa", "name": null }, { "creator_type": "author", "first_name": "Mikiko", "last_name": "Sodeoka", "name": null }, { "creator_type": "author", "first_name": "Yutaka", "last_name": "Ito", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/s10858-016-0059-4" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "27631409" } }, "mesh": [ { "descriptor": "Chelating Agents", "descriptor_ui": "D002614", "major_topic": false }, { "descriptor": "HeLa Cells", "descriptor_ui": "D006367", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Isotope Labeling", "descriptor_ui": "D007553", "major_topic": false }, { "descriptor": "Lanthanoid Series Elements", "descriptor_ui": "D028581", "major_topic": false }, { "descriptor": "Magnetic Resonance Spectroscopy", "descriptor_ui": "D009682", "major_topic": true }, { "descriptor": "Molecular Docking Simulation", "descriptor_ui": "D062105", "major_topic": false }, { "descriptor": "Molecular Dynamics Simulation", "descriptor_ui": "D056004", "major_topic": false }, { "descriptor": "Molecular Structure", "descriptor_ui": "D015394", "major_topic": false }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": false }, { "descriptor": "Protein Conformation", "descriptor_ui": "D011487", "major_topic": false }, { "descriptor": "Protein Stability", "descriptor_ui": "D055550", "major_topic": false }, { "descriptor": "Proteins", "descriptor_ui": "D011506", "major_topic": false }, { "descriptor": "Ubiquitin", "descriptor_ui": "D025801", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016 Oct", "date_precision": "unknown", "issue": "2", "normalized_date": null, "pages": "99-110", "proceedings_title": null, "publisher": "", "title": "Journal of biomolecular NMR", "volume": "66", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "A new carbamidemethyl-linked lanthanoid chelating tag for PCS NMR spectroscopy of proteins in living HeLa cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Insulin resistance is a condition in which cells are defective in response to the actions of insulin in tissue glucose uptake. Overstimulation of beta-adrenergic receptors (betaARs) leads to the development of heart failure and is associated with the pathogenesis of insulin resistance in the heart. However, the mechanisms by which sustained betaAR stimulation affects insulin resistance in the heart are incompletely understood. In this study, we demonstrate that sustained betaAR stimulation resulted in the inhibition of insulin-induced glucose uptake, and a reduction of insulin induced glucose transporter (GLUT)4 expression that were mediated by the beta2AR subtype in cardiomyocytes and heart tissue. Overstimulation of beta2AR inhibited the insulin-induced translocation of GLUT4 to the plasma membrane of cardiomyocytes. Additionally, betaAR mediated cardiac insulin resistance by reducing glucose uptake and GLUT4 expression via the cAMP-dependent and protein kinase A-dependent pathways. Treatment with beta-blockers, including propranolol and metoprolol antagonized isoproterenol-mediated insulin resistance in the heart. The data in this present study confirm a critical role for protein kinase A in betaAR-mediated insulin resistance.", "classifications": [ { "id": "Nishida", "label": "Group Nishida", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Supachoke", "last_name": "Mangmool", "name": null }, { "creator_type": "author", "first_name": "Tananat", "last_name": "Denkaew", "name": null }, { "creator_type": "author", "first_name": "Sarawuth", "last_name": "Phosri", "name": null }, { "creator_type": "author", "first_name": "Darawan", "last_name": "Pinthong", "name": null }, { "creator_type": "author", "first_name": "Warisara", "last_name": "Parichatikanond", "name": null }, { "creator_type": "author", "first_name": "Tsukasa", "last_name": "Shimauchi", "name": null }, { "creator_type": "author", "first_name": "Motohiro", "last_name": "Nishida", "name": null } ], "identifiers": { "doi": { "normalized": "10.1210/me.2015-1201" }, "pmcid": { "normalized": "PMC4695632" }, "pmid": { "normalized": "26652903" } }, "mesh": [ { "descriptor": "Adrenergic beta-Agonists", "descriptor_ui": "D000318", "major_topic": false }, { "descriptor": "Adrenergic beta-Antagonists", "descriptor_ui": "D000319", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cyclic AMP-Dependent Protein Kinases", "descriptor_ui": "D017868", "major_topic": false }, { "descriptor": "Glucose Transporter Type 4", "descriptor_ui": "D051275", "major_topic": false }, { "descriptor": "HEK293 Cells", "descriptor_ui": "D057809", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Insulin Resistance", "descriptor_ui": "D007333", "major_topic": false }, { "descriptor": "Isoproterenol", "descriptor_ui": "D007545", "major_topic": false }, { "descriptor": "Metoprolol", "descriptor_ui": "D008790", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Myocardium", "descriptor_ui": "D009206", "major_topic": false }, { "descriptor": "Myocytes, Cardiac", "descriptor_ui": "D032383", "major_topic": false }, { "descriptor": "Propranolol", "descriptor_ui": "D011433", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Receptors, Adrenergic, beta", "descriptor_ui": "D011943", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016 Jan", "date_precision": "unknown", "issue": "1", "normalized_date": null, "pages": "118-132", "proceedings_title": null, "publisher": "", "title": "Molecular endocrinology (Baltimore, Md.)", "volume": "30", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Sustained betaAR Stimulation Mediates Cardiac Insulin Resistance in a PKA-Dependent Manner.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Neurotrophic factors and their receptors play a central role in neuronal survival. Since neurons have a highly polarized morphology, target-derived neurotrophic factor signaling is transported retrogradely along the axon to the cell body. A body of evidence suggests that retrograde transport of the neurotrophic factors and their receptors is required for signal propagation. Retrograde transport of neurotrophic factor signaling is crucial not only for neuronal development, but also for preventing neuronal degeneration. Thus, elucidating the mechanism of retrograde transport will lead to insights into the developmental mechanisms of the nervous system as well as contribute to the establishment of novel therapies for neurodegenerative diseases. In this article, we will review the recent progress made in research of retrograde trafficking and discuss its physiological significance.", "classifications": [ { "id": "Enomoto", "label": "Group Enomoto", "parent": "Enomoto", "type": "group" }, { "id": "Enomoto", "label": "Team Enomoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Keisuke", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Hideki", "last_name": "Enomoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1093/jb/mvw037" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "27318359" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Central Nervous System", "descriptor_ui": "D002490", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Nerve Growth Factors", "descriptor_ui": "D009414", "major_topic": false }, { "descriptor": "Neurodegenerative Diseases", "descriptor_ui": "D019636", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": true } ], "publication": { "conference_name": null, "date": "2016 Aug", "date_precision": "unknown", "issue": "2", "normalized_date": null, "pages": "77-85", "proceedings_title": null, "publisher": "", "title": "Journal of biochemistry", "volume": "160", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Retrograde transport of neurotrophic factor signaling: implications in neuronal development and pathogenesis.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "OBJECTIVE: The aim of the study was to investigate the associations of amino acids and other polar metabolites with metabolic syndrome (MetS) in postmenopausal women in a lean Asian population. METHODS: The participants were 1,422 female residents enrolled in a cohort study from April to August 2012. MetS was defined according to the National Cholesterol Education Program Adult Treatment Panel III modified for Japanese women. Associations were examined between MetS and 78 metabolites assayed in fasting plasma samples using capillary electrophoresis-mass spectrometry. Replication analysis was performed to confirm the robustness of the results in a separate population created by random allocation. RESULTS: Analysis was performed for 877 naturally postmenopausal women, including 594 in the original population and 283 in the replication population. The average age, body mass index, and levels of high- and low-density lipoprotein cholesterol of the entire population were 64.6 years, 23.0 kg/m, 72.1 mg/dL, and 126.1 mg/dL, respectively. There was no significant difference in low-density lipoprotein cholesterol levels between women with and without MetS. Thirteen metabolites were significantly related to MetS: multiple plasma amino acids were elevated in women with MetS, including branched-chain amino acids, alanine, glutamate, and proline; and alpha-aminoadipate, which is generated by lysine degradation, was also significantly increased. CONCLUSIONS: Our large-scale metabolomic profiling indicates that Japanese postmenopausal women with MetS have abnormal polar metabolites, suggesting altered catabolic pathways. These results may help to understand metabolic disturbance, including in persons with normal body mass index and relatively high levels of high-density lipoprotein cholesterol, and may have clinical utility based on further studies.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Miho", "last_name": "Iida", "name": null }, { "creator_type": "author", "first_name": "Sei", "last_name": "Harada", "name": null }, { "creator_type": "author", "first_name": "Ayako", "last_name": "Kurihara", "name": null }, { "creator_type": "author", "first_name": "Kota", "last_name": "Fukai", "name": null }, { "creator_type": "author", "first_name": "Kazuyo", "last_name": "Kuwabara", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Sugiyama", "name": null }, { "creator_type": "author", "first_name": "Ayano", "last_name": "Takeuchi", "name": null }, { "creator_type": "author", "first_name": "Tomonori", "last_name": "Okamura", "name": null }, { "creator_type": "author", "first_name": "Miki", "last_name": "Akiyama", "name": null }, { "creator_type": "author", "first_name": "Yuji", "last_name": "Nishiwaki", "name": null }, { "creator_type": "author", "first_name": "Asako", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Akiyoshi", "last_name": "Hirayama", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Sugimoto", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Masaru", "last_name": "Tomita", "name": null }, { "creator_type": "author", "first_name": "Kouji", "last_name": "Banno", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Aoki", "name": null }, { "creator_type": "author", "first_name": "Toru", "last_name": "Takebayashi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1097/gme.0000000000000630" }, "pmcid": { "normalized": "PMC4927224" }, "pmid": { "normalized": "27070805" } }, "mesh": [ { "descriptor": "2-Aminoadipate Transaminase", "descriptor_ui": "D051307", "major_topic": false }, { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Alanine", "descriptor_ui": "D000409", "major_topic": false }, { "descriptor": "Amino Acids", "descriptor_ui": "D000596", "major_topic": false }, { "descriptor": "Amino Acids, Branched-Chain", "descriptor_ui": "D000597", "major_topic": false }, { "descriptor": "Asian People", "descriptor_ui": "D044466", "major_topic": false }, { "descriptor": "Body Mass Index", "descriptor_ui": "D015992", "major_topic": false }, { "descriptor": "Cholesterol, HDL", "descriptor_ui": "D008076", "major_topic": false }, { "descriptor": "Cholesterol, LDL", "descriptor_ui": "D008078", "major_topic": false }, { "descriptor": "Cohort Studies", "descriptor_ui": "D015331", "major_topic": false }, { "descriptor": "Fasting", "descriptor_ui": "D005215", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Glutamic Acid", "descriptor_ui": "D018698", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Japan", "descriptor_ui": "D007564", "major_topic": false }, { "descriptor": "Metabolic Syndrome", "descriptor_ui": "D024821", "major_topic": false }, { "descriptor": "Metabolome", "descriptor_ui": "D055442", "major_topic": true }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Postmenopause", "descriptor_ui": "D017698", "major_topic": false }, { "descriptor": "Proline", "descriptor_ui": "D011392", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016 Jul", "date_precision": "unknown", "issue": "7", "normalized_date": null, "pages": "749-758", "proceedings_title": null, "publisher": "", "title": "Menopause (New York, N.Y.)", "volume": "23", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Profiling of plasma metabolites in postmenopausal women with metabolic syndrome.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Cell proliferation is crucial to the growth of multicellular organisms, and thus the proper control of cell division is important to prevent developmental arrest or overgrowth. Nevertheless, tools for controlling cell proliferation are still poor in plant. To develop novel tools, we focused on a specific compound family, triarylmethanes, whose members show various antiproliferative activities in animals. By combining organic chemistry to create novel and diverse compounds containing the triarylmethyl moiety and biological screens based on live-cell imaging of a fluorescently labeled tobacco Bright Yellow-2 (BY-2) culture cell line (Nicotiana tabacum), we isolated (3-furyl)diphenylmethane as a strong but partially reversible inhibitor of plant cell division. We also found that this agent had efficient antiproliferative activity in developing organs of Arabidopsis thaliana without causing secondary defects in cell morphology, and induced rapid cell division arrest independent of the cell cycle stage. Given that (3-furyl)diphenylmethane did not affect the growth of a human cell line (HeLa) and a budding yeast (Saccharomyces cerevisiae), it should act specifically on plants. Taking our results together, we propose that the combination of desired chemical synthesis and detailed biological analysis is an effective tool to create novel drugs, and that (3-furyl)diphenylmethane is a specific antiproliferative agent for plants.", "classifications": [ { "id": "Nanbo", "label": "Group Nanbo", "parent": "Tsuchiya", "type": "group" }, { "id": "Tsuchiya", "label": "Team Tsuchiya", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Masakazu", "last_name": "Nambo", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Kurihara", "name": null }, { "creator_type": "author", "first_name": "Tomomi", "last_name": "Yamada", "name": null }, { "creator_type": "author", "first_name": "Taeko", "last_name": "Nishiwaki-Ohkawa", "name": null }, { "creator_type": "author", "first_name": "Naoya", "last_name": "Kadofusa", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Kimata", "name": null }, { "creator_type": "author", "first_name": "Keiko", "last_name": "Kuwata", "name": null }, { "creator_type": "author", "first_name": "Masaaki", "last_name": "Umeda", "name": null }, { "creator_type": "author", "first_name": "Minako", "last_name": "Ueda", "name": null } ], "identifiers": { "doi": { "normalized": "10.1093/pcp/pcw140" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "27519314" } }, "mesh": [ { "descriptor": "Arabidopsis", "descriptor_ui": "D017360", "major_topic": false }, { "descriptor": "Benzhydryl Compounds", "descriptor_ui": "D001559", "major_topic": false }, { "descriptor": "Cell Cycle", "descriptor_ui": "D002453", "major_topic": false }, { "descriptor": "Cell Division", "descriptor_ui": "D002455", "major_topic": true }, { "descriptor": "Cell Proliferation", "descriptor_ui": "D049109", "major_topic": false }, { "descriptor": "Cell Survival", "descriptor_ui": "D002470", "major_topic": false }, { "descriptor": "Chemistry Techniques, Synthetic", "descriptor_ui": "D060326", "major_topic": false }, { "descriptor": "HeLa Cells", "descriptor_ui": "D006367", "major_topic": false }, { "descriptor": "High-Throughput Screening Assays", "descriptor_ui": "D057166", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Molecular Imaging", "descriptor_ui": "D057054", "major_topic": false }, { "descriptor": "Nicotiana", "descriptor_ui": "D014026", "major_topic": false }, { "descriptor": "Organ Specificity", "descriptor_ui": "D009928", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016 Nov", "date_precision": "unknown", "issue": "11", "normalized_date": null, "pages": "2255-2268", "proceedings_title": null, "publisher": "", "title": "Plant & cell physiology", "volume": "57", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Combination of Synthetic Chemistry and Live-Cell Imaging Identified a Rapid Cell Division Inhibitor in Tobacco and Arabidopsis thaliana.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Sei", "last_name": "Harada", "name": null }, { "creator_type": "author", "first_name": "Toru", "last_name": "Takebayashi", "name": null }, { "creator_type": "author", "first_name": "Ayako", "last_name": "Kurihara", "name": null }, { "creator_type": "author", "first_name": "Miki", "last_name": "Akiyama", "name": null }, { "creator_type": "author", "first_name": "Asako", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Yoko", "last_name": "Hatakeyama", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Sugiyama", "name": null }, { "creator_type": "author", "first_name": "Kazuyo", "last_name": "Kuwabara", "name": null }, { "creator_type": "author", "first_name": "Ayano", "last_name": "Takeuchi", "name": null }, { "creator_type": "author", "first_name": "Tomonori", "last_name": "Okamura", "name": null }, { "creator_type": "author", "first_name": "Yuji", "last_name": "Nishiwaki", "name": null }, { "creator_type": "author", "first_name": "Taichiro", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Akiyoshi", "last_name": "Hirayama", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Sugimoto", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Masaru", "last_name": "Tomita", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/s12199-016-0519-1" }, "pmcid": { "normalized": "PMC4907931" }, "pmid": { "normalized": "26898210" } }, "mesh": [], "publication": { "conference_name": null, "date": "2016 Jul", "date_precision": "unknown", "issue": "4", "normalized_date": null, "pages": "283-284", "proceedings_title": null, "publisher": "", "title": "Environmental health and preventive medicine", "volume": "21", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Erratum to: Metabolomic profiling reveals novel biomarkers of alcohol intake and alcohol-induced liver injury in community-dwelling men.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "OBJECTIVE: Metabolomics is a promising approach to the identification of biomarkers in plasma. Here, we performed a population-based, cross-sectional study to identify potential biomarkers of alcohol intake and alcohol-induced liver injury by metabolomic profiling using capillary electrophoresis-mass spectrometry (CE-MS). METHODS: Fasting plasma samples were collected from 896 Japanese men who participated in the baseline survey of the Tsuruoka Metabolomics Cohort Study, and 115 polar metabolites were identified and absolutely quantified by CE-MS. Information on daily ethanol intake was collected through a standardized, self-administered questionnaire. The associations between ethanol intake and plasma concentration of metabolites were examined. Relationships between metabolite concentrations or their ratios and serum liver enzyme levels in the highest ethanol intake group (>46.0 g/day) were then examined by linear regression analysis. Replication analysis was conducted in 193 samples collected from independent population of this cohort. RESULTS: Nineteen metabolites were identified to have an association with daily alcohol consumption both in the original and replication population. Three of these metabolites (threonine, glutamine, and guanidinosuccinate) were found to associate well with elevated levels of serum liver enzymes in the highest ethanol intake group, but not in the non-drinker group. We also found that the glutamate/glutamine ratio had a much stronger relation to serum gamma-glutamyltransferase, aspartate transaminase, and alanine transaminase than glutamate or glutamine alone (standardized beta = 0.678, 0.558, 0.498, respectively). CONCLUSIONS: We found 19 metabolites associated with alcohol intake, and three biomarker candidates (threonine, guanidinosuccinate and glutamine) of alcohol-induced liver injury. Glutamate/glutamine ratio might also be good biomarker.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Sei", "last_name": "Harada", "name": null }, { "creator_type": "author", "first_name": "Toru", "last_name": "Takebayashi", "name": null }, { "creator_type": "author", "first_name": "Ayako", "last_name": "Kurihara", "name": null }, { "creator_type": "author", "first_name": "Miki", "last_name": "Akiyama", "name": null }, { "creator_type": "author", "first_name": "Asako", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Yoko", "last_name": "Hatakeyama", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Sugiyama", "name": null }, { "creator_type": "author", "first_name": "Kazuyo", "last_name": "Kuwabara", "name": null }, { "creator_type": "author", "first_name": "Ayano", "last_name": "Takeuchi", "name": null }, { "creator_type": "author", "first_name": "Tomonori", "last_name": "Okamura", "name": null }, { "creator_type": "author", "first_name": "Yuji", "last_name": "Nishiwaki", "name": null }, { "creator_type": "author", "first_name": "Taichiro", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Akiyoshi", "last_name": "Hirayama", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Sugimoto", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Masaru", "last_name": "Tomita", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/s12199-015-0494-y" }, "pmcid": { "normalized": "PMC4693765" }, "pmid": { "normalized": "26459263" } }, "mesh": [ { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Alcohol Drinking", "descriptor_ui": "D000428", "major_topic": false }, { "descriptor": "Biomarkers", "descriptor_ui": "D015415", "major_topic": false }, { "descriptor": "Cross-Sectional Studies", "descriptor_ui": "D003430", "major_topic": false }, { "descriptor": "Electrophoresis, Capillary", "descriptor_ui": "D019075", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Japan", "descriptor_ui": "D007564", "major_topic": false }, { "descriptor": "Liver Diseases, Alcoholic", "descriptor_ui": "D008108", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mass Spectrometry", "descriptor_ui": "D013058", "major_topic": false }, { "descriptor": "Metabolome", "descriptor_ui": "D055442", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016 Jan", "date_precision": "unknown", "issue": "1", "normalized_date": null, "pages": "18-26", "proceedings_title": null, "publisher": "", "title": "Environmental health and preventive medicine", "volume": "21", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Metabolomic profiling reveals novel biomarkers of alcohol intake and alcohol-induced liver injury in community-dwelling men.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "MEK1, an essential component of the mitogen-activated protein kinase (MAPK) pathway, is phosphorylated during activation of the pathway; 12 phosphorylation sites have been identified in human MEK1 by MS-based phosphoproteomic methods. By using Phos-tag SDS-PAGE, we found that multiple variants of MEK1 with different phosphorylation states are constitutively present in typical human cells. The Phos-tag-based strategy, which makes effective use of existing information on the location of phosphorylation sites, permits quantitative time-course profiling of MEK1 phosphospecies in their respective phosphorylation states. By subsequent immunoblotting with an anti-HaloTag antibody, we analyzed a HaloTag-fused MEK1 protein and 12 potential phosphorylation-site-directed mutants of the protein transiently expressed in HEK 293 cells. This strategy revealed that MEK1 is constitutively and mainly phosphorylated at the Thr-292, Ser-298, Thr-386, and Thr-388 residues in vivo, and that combinations of phosphorylations at these four residues produce at least six phosphorylated variants of MEK1. Like the levels of phosphorylation of the Ser-218 and Ser-222 residues by RAF1, which have been well studied, the phosphorylation statuses of Thr-292, Ser-298, Thr-386, and Thr-388 residues vary widely during activation and deactivation of the MAPK pathway. Furthermore, we demonstrated inhibitor-specific profiling of MEK1 phosphospecies by using three MEK inhibitors: TAK-733, PD98059, and U0126.", "classifications": [ { "id": "Takekawa", "label": "Group Takekawa", "parent": "Takekawa", "type": "group" }, { "id": "Takekawa", "label": "Team Takekawa", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Eiji", "last_name": "Kinoshita", "name": null }, { "creator_type": "author", "first_name": "Emiko", "last_name": "Kinoshita-Kikuta", "name": null }, { "creator_type": "author", "first_name": "Yuji", "last_name": "Kubota", "name": null }, { "creator_type": "author", "first_name": "Mutsuhiro", "last_name": "Takekawa", "name": null }, { "creator_type": "author", "first_name": "Tohru", "last_name": "Koike", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/pmic.201500494" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "27169363" } }, "mesh": [ { "descriptor": "Amino Acids", "descriptor_ui": "D000596", "major_topic": false }, { "descriptor": "Electrophoresis, Polyacrylamide Gel", "descriptor_ui": "D004591", "major_topic": false }, { "descriptor": "Epidermal Growth Factor", "descriptor_ui": "D004815", "major_topic": false }, { "descriptor": "HEK293 Cells", "descriptor_ui": "D057809", "major_topic": false }, { "descriptor": "HeLa Cells", "descriptor_ui": "D006367", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "MAP Kinase Kinase 1", "descriptor_ui": "D048369", "major_topic": false }, { "descriptor": "MAP Kinase Signaling System", "descriptor_ui": "D020935", "major_topic": true }, { "descriptor": "Phosphorylation", "descriptor_ui": "D010766", "major_topic": false }, { "descriptor": "Proteomics", "descriptor_ui": "D040901", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016 Jul", "date_precision": "unknown", "issue": "13", "normalized_date": null, "pages": "1825-1836", "proceedings_title": null, "publisher": "", "title": "Proteomics", "volume": "16", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "A Phos-tag SDS-PAGE method that effectively uses phosphoproteomic data for profiling the phosphorylation dynamics of MEK1.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Microglandular adenosis (MGA) is a rare proliferative lesion of the breast composed of small glands lacking myoepithelial cells and lined by S100-positive, oestrogen receptor (ER)-negative, progesterone receptor (PR)-negative, and HER2-negative epithelial cells. There is evidence to suggest that MGA may constitute a non-obligate precursor of triple-negative breast cancer (TNBC). We sought to define the genomic landscape of pure MGA and of MGA, atypical MGA (AMGA) and associated TNBCs, and to determine whether synchronous MGA, AMGA, and TNBCs would be clonally related. Two pure MGAs and eight cases of MGA and/or AMGA associated with in situ or invasive TNBC were collected, microdissected, and subjected to massively parallel sequencing targeting all coding regions of 236 genes recurrently mutated in breast cancer or related to DNA repair. Pure MGAs lacked clonal non-synonymous somatic mutations and displayed limited copy number alterations (CNAs); conversely, all MGAs (n = 7) and AMGAs (n = 3) associated with TNBC harboured at least one somatic non-synonymous mutation (range 3-14 and 1-10, respectively). In all cases where TNBCs were analyzed, identical TP53 mutations and similar patterns of gene CNAs were found in the MGA and/or AMGA and in the associated TNBC. In the MGA/AMGA associated with TNBC lacking TP53 mutations, somatic mutations affecting PI3K pathway-related genes (eg PTEN, PIK3CA, and INPP4B) and tyrosine kinase receptor signalling-related genes (eg ERBB3 and FGFR2) were identified. At diagnosis, MGAs associated with TNBC were found to display subclonal populations, and clonal shifts in the progression from MGA to AMGA and/or to TNBC were observed. Our results demonstrate the heterogeneity of MGAs, and that MGAs associated with TNBC, but not necessarily pure MGAs, are genetically advanced, clonal, and neoplastic lesions harbouring recurrent mutations in TP53 and/or other cancer genes, supporting the notion that a subset of MGAs and AMGAs may constitute non-obligate precursors of TNBCs.", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Elena", "last_name": "Guerini-Rocco", "name": null }, { "creator_type": "author", "first_name": "Salvatore", "last_name": "Piscuoglio", "name": null }, { "creator_type": "author", "first_name": "Charlotte K. Y.", "last_name": "Ng", "name": null }, { "creator_type": "author", "first_name": "Felipe C.", "last_name": "Geyer", "name": null }, { "creator_type": "author", "first_name": "Maria R.", "last_name": "De Filippo", "name": null }, { "creator_type": "author", "first_name": "Carey A.", "last_name": "Eberle", "name": null }, { "creator_type": "author", "first_name": "Muzaffar", "last_name": "Akram", "name": null }, { "creator_type": "author", "first_name": "Nicola", "last_name": "Fusco", "name": null }, { "creator_type": "author", "first_name": "Shu", "last_name": "Ichihara", "name": null }, { "creator_type": "author", "first_name": "Rita A.", "last_name": "Sakr", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null }, { "creator_type": "author", "first_name": "Anne", "last_name": "Vincent-Salomon", "name": null }, { "creator_type": "author", "first_name": "Emad A.", "last_name": "Rakha", "name": null }, { "creator_type": "author", "first_name": "Ian O.", "last_name": "Ellis", "name": null }, { "creator_type": "author", "first_name": "Y. Hannah", "last_name": "Wen", "name": null }, { "creator_type": "author", "first_name": "Britta", "last_name": "Weigelt", "name": null }, { "creator_type": "author", "first_name": "Stuart J.", "last_name": "Schnitt", "name": null }, { "creator_type": "author", "first_name": "Jorge S.", "last_name": "Reis-Filho", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/path.4691" }, "pmcid": { "normalized": "PMC4962789" }, "pmid": { "normalized": "26806567" } }, "mesh": [ { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Biomarkers, Tumor", "descriptor_ui": "D014408", "major_topic": false }, { "descriptor": "Carcinoma", "descriptor_ui": "D002277", "major_topic": false }, { "descriptor": "Carcinoma in Situ", "descriptor_ui": "D002278", "major_topic": false }, { "descriptor": "Disease Progression", "descriptor_ui": "D018450", "major_topic": false }, { "descriptor": "DNA Mutational Analysis", "descriptor_ui": "D004252", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Fibrocystic Breast Disease", "descriptor_ui": "D005348", "major_topic": false }, { "descriptor": "Genetic Predisposition to Disease", "descriptor_ui": "D020022", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Immunohistochemistry", "descriptor_ui": "D007150", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": true }, { "descriptor": "Phenotype", "descriptor_ui": "D010641", "major_topic": false }, { "descriptor": "Precancerous Conditions", "descriptor_ui": "D011230", "major_topic": false }, { "descriptor": "Retrospective Studies", "descriptor_ui": "D012189", "major_topic": false }, { "descriptor": "Triple Negative Breast Neoplasms", "descriptor_ui": "D064726", "major_topic": false }, { "descriptor": "Tumor Suppressor Protein p53", "descriptor_ui": "D016159", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016 Apr", "date_precision": "unknown", "issue": "5", "normalized_date": null, "pages": "677-688", "proceedings_title": null, "publisher": "", "title": "The Journal of pathology", "volume": "238", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Microglandular adenosis associated with triple-negative breast cancer is a neoplastic lesion of triple-negative phenotype harbouring TP53 somatic mutations.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Mild hypoxia increases ventilation, but severe hypoxia depresses it. The mechanism of hypoxic ventilatory depression, in particular, the functional role of the cerebrum, is not fully understood. Recent progress in glial physiology has provided evidence that astrocytes play active roles in information processing in various brain functions. We investigated the hypothesis that astrocytic activation is necessary to maintain the cerebral function and ventilation in hypoxia, by examining the responses of EEG and ventilation to severe hypoxia before and after administration of a modulator of astrocytic function, arundic acid, in unanesthetized mice. Ventilatory parameters were measured by whole body plethysmography. When hypoxic ventilatory depression occurred, gamma frequency band of EEG was suppressed. Arundic acid further suppressed ventilation, and the EEG power was suppressed in a dose-dependent manner. Arundic acid also suppressed hypoxia-induced c-Fos expression in the hypothalamus. We conclude that severe hypoxia suppresses the cerebral function which could reduce the stimulus to the brainstem resulting in ventilatory depression. Astrocytic activation in hypoxia may counteract both cerebral and ventilatory suppression.", "classifications": [ { "id": "Yokota", "label": "Group Yokota", "parent": "Enomoto", "type": "group" }, { "id": "Enomoto", "label": "Team Enomoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Isato", "last_name": "Fukushi", "name": null }, { "creator_type": "author", "first_name": "Kotaro", "last_name": "Takeda", "name": null }, { "creator_type": "author", "first_name": "Shigefumi", "last_name": "Yokota", "name": null }, { "creator_type": "author", "first_name": "Yohei", "last_name": "Hasebe", "name": null }, { "creator_type": "author", "first_name": "Yutaka", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Mieczyslaw", "last_name": "Pokorski", "name": null }, { "creator_type": "author", "first_name": "Jouji", "last_name": "Horiuchi", "name": null }, { "creator_type": "author", "first_name": "Yasumasa", "last_name": "Okada", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.resp.2015.11.011" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "26592145" } }, "mesh": [ { "descriptor": "Analysis of Variance", "descriptor_ui": "D000704", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Astrocytes", "descriptor_ui": "D001253", "major_topic": false }, { "descriptor": "Brain", "descriptor_ui": "D001921", "major_topic": false }, { "descriptor": "Caprylates", "descriptor_ui": "D002210", "major_topic": false }, { "descriptor": "Central Nervous System Agents", "descriptor_ui": "D002491", "major_topic": false }, { "descriptor": "Dose-Response Relationship, Drug", "descriptor_ui": "D004305", "major_topic": false }, { "descriptor": "Electrocorticography", "descriptor_ui": "D000069280", "major_topic": false }, { "descriptor": "Gamma Rhythm", "descriptor_ui": "D065818", "major_topic": false }, { "descriptor": "Hypoxia", "descriptor_ui": "D000860", "major_topic": false }, { "descriptor": "Immunohistochemistry", "descriptor_ui": "D007150", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Plethysmography, Whole Body", "descriptor_ui": "D010993", "major_topic": false }, { "descriptor": "Proto-Oncogene Proteins c-fos", "descriptor_ui": "D016760", "major_topic": false }, { "descriptor": "Respiration", "descriptor_ui": "D012119", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016 Jun", "date_precision": "unknown", "issue": "", "normalized_date": null, "pages": "24-29", "proceedings_title": null, "publisher": "", "title": "Respiratory physiology & neurobiology", "volume": "226", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Effects of arundic acid, an astrocytic modulator, on the cerebral and respiratory functions in severe hypoxia.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: Circadian rhythm disruptions can cause various health disorders. The present study evaluated associations between single nucleotide polymorphisms in the core circadian gene clock circadian regulator (CLOCK) and the prevalence of type 2 diabetes (T2D) in the Japanese population. METHODS: Cross-sectional data were analyzed from 2485 subjects (1243 men, 1242 women; age 35-69 years) enrolled in the baseline surveys of the Japan Multi-Institutional Collaborative Cohort (J-MICC) Study. Associations between three CLOCK gene polymorphisms (rs1801260, rs3736544, and rs4864548) and the prevalence of obesity (body mass index [BMI] >/=25 kg/m(2) ), overweight (BMI >/=23 kg/m(2) ), and T2D were evaluated by logistic regression analyses; haplotype analysis and stratified analyses for the prevalence of diabetes were also conducted. RESULTS: Compared with those who were homozygous for the respective major alleles, subjects with the rs1801260 minor allele C had a significantly higher odds ratio (1.5; 95% confidence interval 1.1-2.1) for the prevalence of diabetes after adjustment for potential confounding factors, including BMI. When stratified by overweight, the associations between rs1801260 and the prevalence of diabetes were marked and significant in non-overweight subjects, but not in overweight subjects. The TGA (rs1801260-rs3736544-rs4864548) haplotype was associated with a lower prevalence of diabetes, whereas the CGG haplotype was associated with a higher prevalence of diabetes. CONCLUSIONS: Variant of the CLOCK gene and related haplotypes are associated with the prevalence of T2D in the Japanese population, in which obesity is less common, and the association between CLOCK gene variant at rs1801260 and the prevalence of diabetes is enhanced in normal-weight subjects.", "classifications": [ { "id": "Tanaka", "label": "Group Tanaka", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Hirokazu", "last_name": "Uemura", "name": null }, { "creator_type": "author", "first_name": "Sakurako", "last_name": "Katsuura-Kamano", "name": null }, { "creator_type": "author", "first_name": "Miwa", "last_name": "Yamaguchi", "name": null }, { "creator_type": "author", "first_name": "Kokichi", "last_name": "Arisawa", "name": null }, { "creator_type": "author", "first_name": "Nobuyuki", "last_name": "Hamajima", "name": null }, { "creator_type": "author", "first_name": "Asahi", "last_name": "Hishida", "name": null }, { "creator_type": "author", "first_name": "Sayo", "last_name": "Kawai", "name": null }, { "creator_type": "author", "first_name": "Isao", "last_name": "Oze", "name": null }, { "creator_type": "author", "first_name": "Koichi", "last_name": "Shinchi", "name": null }, { "creator_type": "author", "first_name": "Naoyuki", "last_name": "Takashima", "name": null }, { "creator_type": "author", "first_name": "Sadao", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Noriko", "last_name": "Nakahata", "name": null }, { "creator_type": "author", "first_name": "Haruo", "last_name": "Mikami", "name": null }, { "creator_type": "author", "first_name": "Keizo", "last_name": "Ohnaka", "name": null }, { "creator_type": "author", "first_name": "Nagato", "last_name": "Kuriyama", "name": null }, { "creator_type": "author", "first_name": "Michiaki", "last_name": "Kubo", "name": null }, { "creator_type": "author", "first_name": "Hideo", "last_name": "Tanaka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/1753-0407.12344" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "26374515" } }, "mesh": [ { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Alleles", "descriptor_ui": "D000483", "major_topic": false }, { "descriptor": "Asian People", "descriptor_ui": "D044466", "major_topic": false }, { "descriptor": "Body Mass Index", "descriptor_ui": "D015992", "major_topic": false }, { "descriptor": "CLOCK Proteins", "descriptor_ui": "D056926", "major_topic": false }, { "descriptor": "Cohort Studies", "descriptor_ui": "D015331", "major_topic": false }, { "descriptor": "Cross-Sectional Studies", "descriptor_ui": "D003430", "major_topic": false }, { "descriptor": "Diabetes Mellitus, Type 2", "descriptor_ui": "D003924", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Gene Frequency", "descriptor_ui": "D005787", "major_topic": false }, { "descriptor": "Genetic Predisposition to Disease", "descriptor_ui": "D020022", "major_topic": false }, { "descriptor": "Genotype", "descriptor_ui": "D005838", "major_topic": false }, { "descriptor": "Haplotypes", "descriptor_ui": "D006239", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Japan", "descriptor_ui": "D007564", "major_topic": false }, { "descriptor": "Linkage Disequilibrium", "descriptor_ui": "D015810", "major_topic": false }, { "descriptor": "Logistic Models", "descriptor_ui": "D016015", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Polymorphism, Single Nucleotide", "descriptor_ui": "D020641", "major_topic": true }, { "descriptor": "Prevalence", "descriptor_ui": "D015995", "major_topic": false }, { "descriptor": "Surveys and Questionnaires", "descriptor_ui": "D011795", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016 Sep", "date_precision": "unknown", "issue": "5", "normalized_date": null, "pages": "667-676", "proceedings_title": null, "publisher": "", "title": "Journal of diabetes", "volume": "8", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Variant of the clock circadian regulator (CLOCK) gene and related haplotypes are associated with the prevalence of type 2 diabetes in the Japanese population.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Striga spp. (witchweed) is an obligate parasitic plant that attaches to host roots to deplete them of nutrients. In Sub-Saharan Africa, the most destructive Striga species, Striga hermonthica, parasitizes major food crops affecting two-thirds of the arable land and over 100 million people. One potential weakness in the Striga infection process is the way it senses the presence of a host crop. Striga only germinates in the presence of the plant hormone strigolactone, which exudes from a host root. Hence small molecules that perturb strigolactone signaling may be useful tools for disrupting the Striga lifecycle. Here we developed a chemical screen to suppress strigolactone signaling in the model plant Arabidopsis. One compound, soporidine, specifically inhibited a S. hermonthica strigolactone receptor and inhibited the parasite's germination. This indicates that strigolactone-based screens using Arabidopsis are useful in identifying lead compounds to combat Striga infestations.", "classifications": [ { "id": "Tsuchiya", "label": "Group Tsuchiya", "parent": "Tsuchiya", "type": "group" }, { "id": "Tsuchiya", "label": "Team Tsuchiya", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Duncan", "last_name": "Holbrook-Smith", "name": null }, { "creator_type": "author", "first_name": "Shigeo", "last_name": "Toh", "name": null }, { "creator_type": "author", "first_name": "Yuichiro", "last_name": "Tsuchiya", "name": null }, { "creator_type": "author", "first_name": "Peter", "last_name": "McCourt", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/nchembio.2129" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "27428512" } }, "mesh": [ { "descriptor": "Arabidopsis", "descriptor_ui": "D017360", "major_topic": false }, { "descriptor": "Germination", "descriptor_ui": "D018525", "major_topic": false }, { "descriptor": "Lactones", "descriptor_ui": "D007783", "major_topic": false }, { "descriptor": "Molecular Structure", "descriptor_ui": "D015394", "major_topic": false }, { "descriptor": "Piperidines", "descriptor_ui": "D010880", "major_topic": false }, { "descriptor": "Plant Growth Regulators", "descriptor_ui": "D010937", "major_topic": false }, { "descriptor": "Receptors, Cell Surface", "descriptor_ui": "D011956", "major_topic": false }, { "descriptor": "Small Molecule Libraries", "descriptor_ui": "D054852", "major_topic": false }, { "descriptor": "Striga", "descriptor_ui": "D034362", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016 Sep", "date_precision": "unknown", "issue": "9", "normalized_date": null, "pages": "724-729", "proceedings_title": null, "publisher": "", "title": "Nature chemical biology", "volume": "12", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Small-molecule antagonists of germination of the parasitic plant Striga hermonthica.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Intracellular fluorescence lifetime images of the endogenous fluorophores of nicotinamide adenine dinucleotide (NADH) and flavin adenine dinucleotide (FAD), which are well known as autofluorescence chromophores, were obtained from rat normal fibroblast cells (WFB) and H-ras oncogene-transfected cancer cells among WFB (W31). The average lifetime of the NADH and FAD autofluorescence was shorter in cancer cells than in normal cells, indicating that the difference in metabolism between healthy and cancer cells alters the conditions for coenzymes such as NADH and FAD and that the autofluorescence lifetime measurement of NADH and FAD is applicable for the noninvasive diagnosis of cancer cells. The pico- and nano-second time-resolved fluorescence spectra of NADH obtained with different time windows were similar in normal and cancer cells, indicating that every fluorescence decay component gives the same spectrum in both cell types. These results as well as the fluorescence lifetime images of exogenous fluorophores stained with sodium pheophorbide a in normal and cancer cells suggest that the difference in the fluorescence lifetime between normal and cancer cells cannot be attributed to a difference in the intracellular pH or refractive index but to the difference in the bound condition between proteins and NADH or FAD under the different intracellular environments of normal and cancer cells.", "classifications": [ { "id": "Nakabayashi", "label": "Group Nakabayashi", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Kamlesh", "last_name": "Awasthi", "name": null }, { "creator_type": "author", "first_name": "Daiki", "last_name": "Moriya", "name": null }, { "creator_type": "author", "first_name": "Takakazu", "last_name": "Nakabayashi", "name": null }, { "creator_type": "author", "first_name": "Liming", "last_name": "Li", "name": null }, { "creator_type": "author", "first_name": "Nobuhiro", "last_name": "Ohta", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.jphotobiol.2016.10.023" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "27842280" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Fluorescence", "descriptor_ui": "D005453", "major_topic": false }, { "descriptor": "Neoplasms", "descriptor_ui": "D009369", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016 Dec", "date_precision": "unknown", "issue": "", "normalized_date": null, "pages": "256-265", "proceedings_title": null, "publisher": "", "title": "Journal of photochemistry and photobiology. B, Biology", "volume": "165", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Sensitive detection of intracellular environment of normal and cancer cells by autofluorescence lifetime imaging.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: Helicobacter pylori is the primary cause of gastric cancer, but about 9% of cases harbor Epstein-Barr virus (EBV) in the tumor cells. There is limited evidence on the possible interaction or antagonism between these infectious agents in gastric carcinogenesis. METHODS: We compared H. pylori serologic profiles of EBV-positive (n = 58) and EBV-negative (n = 111) noncardia gastric cancer patients from the United States National Cancer Institute's International EBV-Gastric Cancer Consortium. EBV positivity of tumors was assessed by in situ hybridization. Serum levels of 15 antibodies to immunogenic proteins of H. pylori (Cad, CagA, Cagδ, CagM, Catalase, GroEL, HcpC, HP0231, HP0305, HpaA, HyuA, NapA, Omp, UreA, VacA) were assessed using bead-based multiplex serology. Logistic regression models were used to adjust odds ratios (OR) for country, age, sex, and year of diagnosis. RESULTS: Seropositivity to individual proteins ranged up to 90% overall. Antibodies to Catalase were borderline associated with tumor EBV positivity (adjusted OR = 3.15, p = .0024, Bonferroni corrected p = .036). Distributions of other antibodies did not vary by tumor EBV status. CONCLUSION: Similarity of host-response indicates the essential etiological role of H. pylori in EBV-positive gastric cancer.", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "M. Constanza", "last_name": "Camargo", "name": null }, { "creator_type": "author", "first_name": "Kyoung-Mee", "last_name": "Kim", "name": null }, { "creator_type": "author", "first_name": "Keitaro", "last_name": "Matsuo", "name": null }, { "creator_type": "author", "first_name": "Javier", "last_name": "Torres", "name": null }, { "creator_type": "author", "first_name": "Linda M.", "last_name": "Liao", "name": null }, { "creator_type": "author", "first_name": "Douglas R.", "last_name": "Morgan", "name": null }, { "creator_type": "author", "first_name": "Angelika", "last_name": "Michel", "name": null }, { "creator_type": "author", "first_name": "Tim", "last_name": "Waterboer", "name": null }, { "creator_type": "author", "first_name": "Jovanny", "last_name": "Zabaleta", "name": null }, { "creator_type": "author", "first_name": "Ricardo L.", "last_name": "Dominguez", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null }, { "creator_type": "author", "first_name": "Sung", "last_name": "Kim", "name": null }, { "creator_type": "author", "first_name": "Erick R.", "last_name": "Rocha-Guevara", "name": null }, { "creator_type": "author", "first_name": "Jolanta", "last_name": "Lissowska", "name": null }, { "creator_type": "author", "first_name": "Michael", "last_name": "Pawlita", "name": null }, { "creator_type": "author", "first_name": "Charles S.", "last_name": "Rabkin", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/hel.12249" }, "pmcid": { "normalized": "PMC5003173" }, "pmid": { "normalized": "26251258" } }, "mesh": [ { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Antibodies, Bacterial", "descriptor_ui": "D000907", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Helicobacter Infections", "descriptor_ui": "D016481", "major_topic": false }, { "descriptor": "Helicobacter pylori", "descriptor_ui": "D016480", "major_topic": false }, { "descriptor": "Herpesvirus 4, Human", "descriptor_ui": "D004854", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Stomach Neoplasms", "descriptor_ui": "D013274", "major_topic": false }, { "descriptor": "United States", "descriptor_ui": "D014481", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016 Apr", "date_precision": "unknown", "issue": "2", "normalized_date": null, "pages": "153-157", "proceedings_title": null, "publisher": "", "title": "Helicobacter", "volume": "21", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Anti-Helicobacter pylori Antibody Profiles in Epstein-Barr virus (EBV)-Positive and EBV-Negative Gastric Cancer.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Redox signaling is a key modulator of oxidative stress induced by nonspecific insults of biological molecules generated by reactive oxygen species. Current redox biology is revisiting the traditional concept of oxidative stress, such that toxic effects of reactive oxygen species are protected by diverse antioxidant systems upregulated by oxidative stress responses that are physiologically mediated by redox-dependent cell signaling pathways. Redox signaling is thus precisely regulated by endogenous electrophilic substances that are generated from reactive oxygen species and nitric oxide and its derivative reactive species during stress responses. Among electrophiles formed endogenously, 8-nitroguanosine 3',5'-cyclic monophosphate (8-nitro-cGMP) has unique cell signaling functions, and pathways for its biosynthesis, signaling mechanism, and metabolism in cells have been clarified. Reactive sulfur species such as cysteine hydropersulfides that are abundant in cells are likely involved in 8-nitro-cGMP metabolism. These new aspects of redox biology may stimulate innovative and multidisciplinary research in cell and stem cell biology; infectious diseases, cancer, metabolic syndrome, ageing, and neurodegenerative diseases; and other oxidative stress-related disorders. This review focuses on the most recent progress in the biosynthesis, cell signaling, and metabolism of 8-nitro-cGMP, which is a likely target for drug development and lead to discovery of novel therapeutics for many diseases.", "classifications": [ { "id": "Akaike", "label": "Group Akaike", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Group Nishida", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Motohiro", "last_name": "Nishida", "name": null }, { "creator_type": "author", "first_name": "Yoshito", "last_name": "Kumagai", "name": null }, { "creator_type": "author", "first_name": "Hideshi", "last_name": "Ihara", "name": null }, { "creator_type": "author", "first_name": "Shigemoto", "last_name": "Fujii", "name": null }, { "creator_type": "author", "first_name": "Hozumi", "last_name": "Motohashi", "name": null }, { "creator_type": "author", "first_name": "Takaaki", "last_name": "Akaike", "name": null } ], "identifiers": { "doi": { "normalized": "10.3164/jcbn.15-111" }, "pmcid": { "normalized": "PMC4788399" }, "pmid": { "normalized": "27013774" } }, "mesh": [], "publication": { "conference_name": null, "date": "2016 Mar", "date_precision": "unknown", "issue": "2", "normalized_date": null, "pages": "91-98", "proceedings_title": null, "publisher": "", "title": "Journal of clinical biochemistry and nutrition", "volume": "58", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Redox signaling regulated by electrophiles and reactive sulfur species.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Morphogenesis in multicellular organisms is accompanied by apoptotic cell behaviors: cell shrinkage and cell disappearance. The mechanical effects of these behaviors are spatiotemporally regulated within multicellular dynamics to achieve proper tissue sizes and shapes in three-dimensional (3D) space. To analyze 3D multicellular dynamics, 3D vertex models have been suggested, in which a reversible network reconnection (RNR) model has successfully expressed 3D cell rearrangements during large deformations. To analyze the effects of apoptotic cell behaviors on 3D multicellular morphogenesis, we modeled cell apoptosis based on the RNR model framework. Cell shrinkage was modeled by the potential energy as a function of individual cell times during the apoptotic phase. Cell disappearance was modeled by merging neighboring polyhedrons at their boundary surface according to the topological rules of the RNR model. To establish that the apoptotic cell behaviors could be expressed as modeled, we simulated morphogenesis driven by cell apoptosis in two types of tissue topology: 3D monolayer cell sheet and 3D compacted cell aggregate. In both types of tissue topology, the numerical simulations successfully illustrated that cell aggregates gradually shrank because of successive cell apoptosis. During tissue shrinkage, the number of cells in aggregates decreased while maintaining individual cell size and shape. Moreover, in case of localizing apoptotic cells within a part of the 3D monolayer cell aggregate, the cell apoptosis caused the global tissue bending by pulling on surrounding cells. In case of localizing apoptotic cells on the surface of the 3D compacted cell aggregate, the cell apoptosis caused successive, directional cell rearrangements from the inside to the surface. Thus, the proposed model successfully provided a basis for expressing apoptotic cell behaviors during 3D multicellular morphogenesis based on an RNR model framework.", "classifications": [ { "id": "Eiraku", "label": "Group Eiraku", "parent": "Eiraku", "type": "group" }, { "id": "Okuda", "label": "Group Okuda", "parent": "Imayoshi", "type": "group" }, { "id": "Eiraku", "label": "Team Eiraku", "type": "team" }, { "id": "Imayoshi", "label": "Team Imayoshi", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Satoru", "last_name": "Okuda", "name": null }, { "creator_type": "author", "first_name": "Yasuhiro", "last_name": "Inoue", "name": null }, { "creator_type": "author", "first_name": "Mototsugu", "last_name": "Eiraku", "name": null }, { "creator_type": "author", "first_name": "Taiji", "last_name": "Adachi", "name": null }, { "creator_type": "author", "first_name": "Yoshiki", "last_name": "Sasai", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/s10237-015-0724-7" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "26361766" } }, "mesh": [ { "descriptor": "Apoptosis", "descriptor_ui": "D017209", "major_topic": true }, { "descriptor": "Cell Size", "descriptor_ui": "D048429", "major_topic": false }, { "descriptor": "Computer Simulation", "descriptor_ui": "D003198", "major_topic": true }, { "descriptor": "Models, Biological", "descriptor_ui": "D008954", "major_topic": true }, { "descriptor": "Morphogenesis", "descriptor_ui": "D009024", "major_topic": true } ], "publication": { "conference_name": null, "date": "2016 Aug", "date_precision": "unknown", "issue": "4", "normalized_date": null, "pages": "805-816", "proceedings_title": null, "publisher": "", "title": "Biomechanics and modeling in mechanobiology", "volume": "15", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Modeling cell apoptosis for simulating three-dimensional multicellular morphogenesis based on a reversible network reconnection framework.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Previous studies suggest that altered peripheral blood circulation might be associated with erythema or inflammation in atopic dermatitis (AD) patients. However, the overall structure of blood vessels and capillaries in AD skin is poorly understood because most studies have involved light-microscopic observation of thin skin sections. In the present study, we compared the 3-dimensional structures of peripheral blood vessels of healthy subjects and AD patients in detail by means of 2-photon microscopy. In skin from healthy subjects, superficial vascular plexus and capillaries originating from flexous blood vessels were observed. However, skin from AD patients contained thickened, flexuous blood vessels, which might be associated with increased blood flow, in both erythematous and nonlesional areas. However, patients with lichenification did not display these morphological changes. Bifurcation of vessels was not observed in either erythematous or lichenification lesions. These results might be helpful for developing new clinical strategies to treat erythema in AD patients.", "classifications": [ { "id": "Nagayama", "label": "Group Nagayama", "parent": "Fujiwara", "type": "group" }, { "id": "Fujiwara", "label": "Team Fujiwara", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Moe", "last_name": "Tsutsumi", "name": null }, { "creator_type": "author", "first_name": "Maki", "last_name": "Fukuda", "name": null }, { "creator_type": "author", "first_name": "Junichi", "last_name": "Kumamoto", "name": null }, { "creator_type": "author", "first_name": "Makiko", "last_name": "Goto", "name": null }, { "creator_type": "author", "first_name": "Sumiko", "last_name": "Denda", "name": null }, { "creator_type": "author", "first_name": "Kenshi", "last_name": "Yamasaki", "name": null }, { "creator_type": "author", "first_name": "Setsuya", "last_name": "Aiba", "name": null }, { "creator_type": "author", "first_name": "Masaharu", "last_name": "Nagayama", "name": null }, { "creator_type": "author", "first_name": "Mitsuhiro", "last_name": "Denda", "name": null } ], "identifiers": { "doi": { "normalized": "10.1097/dad.0000000000000373" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "26332534" } }, "mesh": [ { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Biomarkers", "descriptor_ui": "D015415", "major_topic": false }, { "descriptor": "Capillaries", "descriptor_ui": "D002196", "major_topic": false }, { "descriptor": "Case-Control Studies", "descriptor_ui": "D016022", "major_topic": false }, { "descriptor": "Collagen Type IV", "descriptor_ui": "D024141", "major_topic": false }, { "descriptor": "Dermatitis, Atopic", "descriptor_ui": "D003876", "major_topic": false }, { "descriptor": "Dermis", "descriptor_ui": "D020405", "major_topic": false }, { "descriptor": "Erythema", "descriptor_ui": "D004890", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Fluorescent Antibody Technique, Indirect", "descriptor_ui": "D019084", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Microscopy, Fluorescence, Multiphoton", "descriptor_ui": "D036641", "major_topic": false }, { "descriptor": "Young Adult", "descriptor_ui": "D055815", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016 May", "date_precision": "unknown", "issue": "5", "normalized_date": null, "pages": "363-364", "proceedings_title": null, "publisher": "", "title": "The American Journal of dermatopathology", "volume": "38", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Abnormal Morphology of Blood Vessels in Erythematous Skin From Atopic Dermatitis Patients.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The advent of super-resolution microscopy brought a huge impact to various research fields ranging from the fundamental science to medical and industrial applications. The technological development is still ongoing with involving different scientific disciplines and often changing the standard of optical imaging. In this review, I would like to introduce the recent research progress in super-resolution microscopy as a follow-up for the featured issue in Microscopy (Vol. 64, No. 4, 2015) with discussions especially on the current trends and new directions in the technological development.", "classifications": [ { "id": "Fujita", "label": "Group Fujita", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Katsumasa", "last_name": "Fujita", "name": null } ], "identifiers": { "doi": { "normalized": "10.1093/jmicro/dfw022" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "27385787" } }, "mesh": [ { "descriptor": "Microscopy, Fluorescence", "descriptor_ui": "D008856", "major_topic": false }, { "descriptor": "Optical Imaging", "descriptor_ui": "D061848", "major_topic": false }, { "descriptor": "Photobleaching", "descriptor_ui": "D038761", "major_topic": false }, { "descriptor": "Single Molecule Imaging", "descriptor_ui": "D000072760", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016 Aug", "date_precision": "unknown", "issue": "4", "normalized_date": null, "pages": "275-281", "proceedings_title": null, "publisher": "", "title": "Microscopy (Oxford, England)", "volume": "65", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Follow-up review: recent progress in the development of super-resolution optical microscopy.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "OBJECTIVE: Inflammation is closely involved in the development of type 2 diabetes, and cigarette smoking acts as potent inducer of inflammation. We therefore investigated interactions between inflammation-related gene polymorphisms and cigarette smoking on glycated hemoglobin (HbA1c) in the Japanese general population. METHOD: We conducted a cross-sectional study using data collected from 2619 Japanese (1274 males and 1345 females) 40-69 years of age who participated in baseline survey of the Japan Multi-Institutional Collaborative Cohort (J-MICC) Study (2005-2008). Eight polymorphisms in seven genes (interleukin [IL]-1beta, IL-2, IL-4, IL-8, IL-10, IL-13 and tumor necrosis factor-alpha) were determined using the Invader assay. The interactions of smoking and gene polymorphisms on HbA1c levels were analyzed using multiple linear and logistic regression models and analysis of covariance with adjustment for potential confounders. RESULTS: Among the eight polymorphisms, only one significant interaction was detected for IL-1beta T-31C (P < 0.0001). Among the subjects carrying TT genotype, current heavy smokers (>/= 20 cigarettes/day) had higher HbA1c (5.83 [95% confidence interval 5.67-5.99] %) versus all other smoking status groups (never 5.49 [5.41-5.56] %, former 5.54 [5.43-5.65] %, current moderate [< 20 cigarettes/day] 5.50 [5.30-5.69] %), whereas such differences were not observed in the subjects with C allele. The logistic regression analyses regarding high-normal HbA1c levels showed a similar pattern of results. CONCLUSION: Smoking status did not interact with any other inflammation-related polymorphisms except for IL-1beta T-31C. Heavy smokers harboring the TT genotype of IL-1beta T-31C polymorphism show a greater adverse effect of smoking on HbA1c levels among Japanese middle-aged subjects.", "classifications": [ { "id": "Tanaka", "label": "Group Tanaka", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yuichiro", "last_name": "Nishida", "name": null }, { "creator_type": "author", "first_name": "Megumi", "last_name": "Hara", "name": null }, { "creator_type": "author", "first_name": "Tatsuhiko", "last_name": "Sakamoto", "name": null }, { "creator_type": "author", "first_name": "Koichi", "last_name": "Shinchi", "name": null }, { "creator_type": "author", "first_name": "Sayo", "last_name": "Kawai", "name": null }, { "creator_type": "author", "first_name": "Mariko", "last_name": "Naito", "name": null }, { "creator_type": "author", "first_name": "Nobuyuki", "last_name": "Hamajima", "name": null }, { "creator_type": "author", "first_name": "Aya", "last_name": "Kadota", "name": null }, { "creator_type": "author", "first_name": "Sadao", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Rie", "last_name": "Ibusuki", "name": null }, { "creator_type": "author", "first_name": "Akie", "last_name": "Hirata", "name": null }, { "creator_type": "author", "first_name": "Miwa", "last_name": "Yamaguchi", "name": null }, { "creator_type": "author", "first_name": "Nagato", "last_name": "Kuriyama", "name": null }, { "creator_type": "author", "first_name": "Isao", "last_name": "Oze", "name": null }, { "creator_type": "author", "first_name": "Haruo", "last_name": "Mikami", "name": null }, { "creator_type": "author", "first_name": "Michiaki", "last_name": "Kubo", "name": null }, { "creator_type": "author", "first_name": "Hideo", "last_name": "Tanaka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.pmedr.2016.03.010" }, "pmcid": { "normalized": "PMC4929182" }, "pmid": { "normalized": "27419029" } }, "mesh": [], "publication": { "conference_name": null, "date": "2016 Jun", "date_precision": "unknown", "issue": "", "normalized_date": null, "pages": "288-295", "proceedings_title": null, "publisher": "", "title": "Preventive medicine reports", "volume": "3", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Influence of cigarette smoking and inflammatory gene polymorphisms on glycated hemoglobin in the Japanese general population.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Primordial germ cells (PGCs) are the foundation of totipotency and vital for reproduction and heredity. PGCs in mice arise from the epiblast around Embryonic Day (E) 7.0, migrate through the hindgut endoderm, and colonize and proliferate in the embryonic gonads until around E13.5 prior to their differentiation either into prospermatogonia or oogonia. PRDM1, a transcriptional repressor, plays an essential role in PGC specification that includes robustly repressing a somatic mesodermal program. Using an inducible conditional knockout system, we show here that PRDM1 is critically required throughout PGC development. When Prdm1 was deleted in migrating PGCs at E9.5 or E10.5, or in male gonadal PGCs at E11.5, PGCs were eliminated by apoptosis from around E10.5, E11.5, or E13.5, respectively. When Prdm1 was deleted in female gonadal PGCs at E11.5, PGCs progressed into the first meiotic prophase in an apparently normal fashion, but the oogonia exhibited an aberrant pachytene phenotype, undergoing abrupt apoptosis from around E16.5. The escape of a fraction of PGCs ( approximately 10%) from the Prdm1 deletion was sufficient to recover fairly normal germ cell pools, both in male and female adults. The key targets of PRDM1 in migrating and/or gonadal PGCs, including genes for development, apoptosis, and prospermatogonial differentiation, showed only a modest overlap with those upon PGC specification, and were enriched with histone H3 lysine 27 trimethylation (H3K27me3). Our findings provide critical insight into the mechanism for maintaining the transcriptional integrity of PGCs.", "classifications": [ { "id": "Yamamoto", "label": "Group Yamamoto", "parent": "Toyoshima", "type": "group" }, { "id": "Toyoshima", "label": "Team Toyoshima", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Chika", "last_name": "Yamashiro", "name": null }, { "creator_type": "author", "first_name": "Takayuki", "last_name": "Hirota", "name": null }, { "creator_type": "author", "first_name": "Kazuki", "last_name": "Kurimoto", "name": null }, { "creator_type": "author", "first_name": "Tomonori", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Yukihiro", "last_name": "Yabuta", "name": null }, { "creator_type": "author", "first_name": "So I.", "last_name": "Nagaoka", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Ohta", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Mitinori", "last_name": "Saitou", "name": null } ], "identifiers": { "doi": { "normalized": "10.1095/biolreprod.115.133256" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "26586842" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Apoptosis", "descriptor_ui": "D017209", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Cell Movement", "descriptor_ui": "D002465", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Gene Expression Regulation, Developmental", "descriptor_ui": "D018507", "major_topic": false }, { "descriptor": "Germ Cells", "descriptor_ui": "D005854", "major_topic": false }, { "descriptor": "Histones", "descriptor_ui": "D006657", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Meiosis", "descriptor_ui": "D008540", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Oogonia", "descriptor_ui": "D009867", "major_topic": false }, { "descriptor": "Ovary", "descriptor_ui": "D010053", "major_topic": false }, { "descriptor": "Positive Regulatory Domain I-Binding Factor 1", "descriptor_ui": "D000074462", "major_topic": false }, { "descriptor": "Pregnancy", "descriptor_ui": "D011247", "major_topic": false }, { "descriptor": "Testis", "descriptor_ui": "D013737", "major_topic": false }, { "descriptor": "Transcription Factors", "descriptor_ui": "D014157", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016 Jan", "date_precision": "unknown", "issue": "1", "normalized_date": null, "pages": "7", "proceedings_title": null, "publisher": "", "title": "Biology of reproduction", "volume": "94", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Persistent Requirement and Alteration of the Key Targets of PRDM1 During Primordial Germ Cell Development in Mice.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "INTRODUCTION: Despite recent advances in cancer therapy, the overall 5-year survival rate of patients with lung cancer remains low. The aim of our study was to search for novel markers for early diagnosis in patients with lung cancer. METHODS: Complementary DNA microarray analysis was performed in primary lung adenocarcinomas and cell lines to search for differentially expressed genes, followed by in vivo and in vitro tumorigenic assays to characterize the oncogenic potential of the candidate genes. Gene body methylation was analyzed by 450K methylation array, bisulfite sequencing, and quantitative methylation-specific polymerase chain reaction assays. In silico analysis of The Cancer Genome Atlas data set was also performed. RESULTS: Inositol-trisphosphate 3-kinase A gene (ITPKA), a kinase with limited tissue distribution, was identified as a potential oncogene. We showed that ITPKA expression is up-regulated in many forms of cancers, including lung and breast cancers, and that overexpressed ITPKA contributes to tumorigenesis. We also demonstrated that ITPKA expression is regulated by epigenetic DNA methylation of ITPKA gene body through modulation of the binding of SP1 transcription factor to the ITPKA promoter. ITPKA gene body displayed low or absent levels of methylation in most normal tissue but was significantly methylated in malignant tumors. In lung cancer, ITPKA gene body methylation first appeared at the in situ carcinoma stage and progressively increased after invasion. CONCLUSIONS: ITPKA is a potential oncogene that it is overexpressed in most tumors, and its overexpression promotes tumorigenesis. ITPKA gene body methylation regulates its expression and thus serves as a novel and potential biomarker for early cancer detection.", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yi-Wei", "last_name": "Wang", "name": null }, { "creator_type": "author", "first_name": "Xiaotu", "last_name": "Ma", "name": null }, { "creator_type": "author", "first_name": "Yu-An", "last_name": "Zhang", "name": null }, { "creator_type": "author", "first_name": "Mei-Jung", "last_name": "Wang", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null }, { "creator_type": "author", "first_name": "Stephen", "last_name": "Lam", "name": null }, { "creator_type": "author", "first_name": "Luc", "last_name": "Girard", "name": null }, { "creator_type": "author", "first_name": "Jeou-Yuan", "last_name": "Chen", "name": null }, { "creator_type": "author", "first_name": "Adi F.", "last_name": "Gazdar", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.jtho.2016.05.010" }, "pmcid": { "normalized": "PMC5555593" }, "pmid": { "normalized": "27234602" } }, "mesh": [ { "descriptor": "Biomarkers, Tumor", "descriptor_ui": "D014408", "major_topic": false }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "DNA Methylation", "descriptor_ui": "D019175", "major_topic": true }, { "descriptor": "Early Detection of Cancer", "descriptor_ui": "D055088", "major_topic": true }, { "descriptor": "Gene Expression Regulation, Neoplastic", "descriptor_ui": "D015972", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Lung Neoplasms", "descriptor_ui": "D008175", "major_topic": false }, { "descriptor": "Phosphotransferases (Alcohol Group Acceptor)", "descriptor_ui": "D017853", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016 Sep", "date_precision": "unknown", "issue": "9", "normalized_date": null, "pages": "1469-1481", "proceedings_title": null, "publisher": "", "title": "Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer", "volume": "11", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "ITPKA Gene Body Methylation Regulates Gene Expression and Serves as an Early Diagnostic Marker in Lung and Other Cancers.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "During the course of our taxonomic investigation of Helicobacter cinaedi, it was realized that the strains isolated from dogs, which have been identified as H. cinaedi, showed different biochemical traits than did the isolates obtained from humans. None of the three dog isolates could reduce nitrate to nitrite, whereas all of the human H. cinaedi isolates could do so. The dog isolates showed a strong positive alkaline phosphatase reaction and could grow at 42 degrees C, however the human isolates showed negative to very weak responses to those tests. The GyrA protein based phylogenetic analysis showed that the three isolates from dogs formed a slightly distinct cluster from the human isolate cluster. Phylogenetic analysis of the 16S rRNA, 23S rRNA, gyrB, and hsp60 gene sequences further confirmed that the dog isolates differed from the human H. cinaedi isolate cluster. The whole-genome in silico DNA similarities of each isolate based on their full genome sequences revealed that the isolates from dogs shared more than 94.9% ANIb (average nucleotide identity based on BLAST), while 94.0% ANIb were found between the isolates from dogs and the humans, including the H. cinaedi type strain ATCC BAA-847(T) (=CCUG 18818(T)). From these data, we propose a new species, 'H. canicola' sp. nov., for the isolates from dogs. The type strain is PAGU 1410(T) (CCUG 33887(T)=LMG 29580(T)).", "classifications": [ { "id": "Akaike", "label": "Group Akaike", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yoshiaki", "last_name": "Kawamura", "name": null }, { "creator_type": "author", "first_name": "Junko", "last_name": "Tomida", "name": null }, { "creator_type": "author", "first_name": "Tohru", "last_name": "Miyoshi-Akiyama", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Okamoto", "name": null }, { "creator_type": "author", "first_name": "Masashi", "last_name": "Narita", "name": null }, { "creator_type": "author", "first_name": "Katsuhiko", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Margo", "last_name": "Cnockaert", "name": null }, { "creator_type": "author", "first_name": "Peter", "last_name": "Vandamme", "name": null }, { "creator_type": "author", "first_name": "Yuji", "last_name": "Morita", "name": null }, { "creator_type": "author", "first_name": "Tomohiro", "last_name": "Sawa", "name": null }, { "creator_type": "author", "first_name": "Takaaki", "last_name": "Akaike", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.syapm.2016.06.004" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "27381809" } }, "mesh": [ { "descriptor": "Alkaline Phosphatase", "descriptor_ui": "D000469", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Chaperonin 60", "descriptor_ui": "D018834", "major_topic": false }, { "descriptor": "DNA Gyrase", "descriptor_ui": "D027081", "major_topic": false }, { "descriptor": "DNA, Bacterial", "descriptor_ui": "D004269", "major_topic": false }, { "descriptor": "Dogs", "descriptor_ui": "D004285", "major_topic": false }, { "descriptor": "Genome, Bacterial", "descriptor_ui": "D016680", "major_topic": false }, { "descriptor": "Helicobacter", "descriptor_ui": "D016998", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Molecular Typing", "descriptor_ui": "D058889", "major_topic": false }, { "descriptor": "Nitrates", "descriptor_ui": "D009566", "major_topic": false }, { "descriptor": "Nitrites", "descriptor_ui": "D009573", "major_topic": false }, { "descriptor": "Phylogeny", "descriptor_ui": "D010802", "major_topic": false }, { "descriptor": "RNA, Ribosomal, 16S", "descriptor_ui": "D012336", "major_topic": false }, { "descriptor": "RNA, Ribosomal, 23S", "descriptor_ui": "D012338", "major_topic": false }, { "descriptor": "Sequence Analysis, DNA", "descriptor_ui": "D017422", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016 Jul", "date_precision": "unknown", "issue": "5", "normalized_date": null, "pages": "307-312", "proceedings_title": null, "publisher": "", "title": "Systematic and applied microbiology", "volume": "39", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Proposal of Helicobacter canicola sp. nov., previously identified as Helicobacter cinaedi, isolated from canines.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "We propose 'trans-omic' analysis for reconstructing global biochemical networks across multiple omic layers by use of both multi-omic measurements and computational data integration. We introduce technologies for connecting multi-omic data based on prior knowledge of biochemical interactions and characterize a biochemical trans-omic network by concepts of a static and dynamic nature. We introduce case studies of metabolism-centric trans-omic studies to show how to reconstruct a biochemical trans-omic network by connecting multi-omic data and how to analyze it in terms of the static and dynamic nature. We propose a trans-ome-wide association study (trans-OWAS) connecting phenotypes with trans-omic networks that reflect both genetic and environmental factors, which can characterize several complex lifestyle diseases as breakdowns in the trans-omic system.", "classifications": [ { "id": "Kuroda", "label": "Group Kuroda", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Katsuyuki", "last_name": "Yugi", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Kubota", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Hatano", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Kuroda", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.tibtech.2015.12.013" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "26806111" } }, "mesh": [ { "descriptor": "Computational Biology", "descriptor_ui": "D019295", "major_topic": false }, { "descriptor": "Gene Regulatory Networks", "descriptor_ui": "D053263", "major_topic": false }, { "descriptor": "Metabolic Networks and Pathways", "descriptor_ui": "D053858", "major_topic": true }, { "descriptor": "Protein Interaction Maps", "descriptor_ui": "D060066", "major_topic": false } ], "publication": { "conference_name": null, "date": "2016 Apr", "date_precision": "unknown", "issue": "4", "normalized_date": null, "pages": "276-290", "proceedings_title": null, "publisher": "", "title": "Trends in biotechnology", "volume": "34", "year": 2016 }, "ssbd": { "database": [], "repository": [] }, "title": "Trans-Omics: How To Reconstruct Biochemical Networks Across Multiple 'Omic' Layers.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "It remains controversial whether the routes from somatic cells to induced pluripotent stem cells (iPSCs) are related to the reverse order of normal developmental processes. Specifically, it remains unaddressed whether or not the differentiated cells become iPSCs through their original tissue stem cell-like state. Previous studies analyzing the reprogramming process mostly used fibroblasts; however, the stem cell characteristics of fibroblasts made it difficult to address this. Here, we generated iPSCs from mouse astrocytes, a type of glial cells, by three (OCT3/4, KLF4, and SOX2), two (OCT3/4 and KLF4), or four (OCT3/4, KLF4, and SOX2 plus c-MYC) factors. Sox1, a neural stem cell (NSC)-specific transcription factor, is transiently up-regulated during reprogramming, and Sox1-positive cells become iPSCs. The up-regulation of Sox1 is essential for OCT3/4- and KLF4-induced reprogramming. Genome-wide analysis revealed that the gene expression profile of Sox1-expressing intermediate-state cells resembles that of NSCs. Furthermore, the intermediate-state cells are able to generate neurospheres, which can differentiate into both neurons and glial cells. Remarkably, during fibroblast reprogramming, neither Sox1 up-regulation nor an increase in neurogenic potential occurs. Our results thus demonstrate that astrocytes are reprogrammed through an NSC-like state.", "classifications": [ { "id": "Yamamoto", "label": "Group Yamamoto", "parent": "Toyoshima", "type": "group" }, { "id": "Toyoshima", "label": "Team Toyoshima", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "May", "last_name": "Nakajima-Koyama", "name": null }, { "creator_type": "author", "first_name": "Joonseong", "last_name": "Lee", "name": null }, { "creator_type": "author", "first_name": "Sho", "last_name": "Ohta", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Eisuke", "last_name": "Nishida", "name": null } ], "identifiers": { "doi": { "normalized": "10.1074/jbc.m115.683466" }, "pmcid": { "normalized": "PMC4692240" }, "pmid": { "normalized": "26553868" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Astrocytes", "descriptor_ui": "D001253", "major_topic": false }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Cellular Reprogramming", "descriptor_ui": "D065150", "major_topic": true }, { "descriptor": "Cellular Reprogramming Techniques", "descriptor_ui": "D000067470", "major_topic": true }, { "descriptor": "Kruppel-Like Factor 4", "descriptor_ui": "D000090062", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Neural Stem Cells", "descriptor_ui": "D058953", "major_topic": false }, { "descriptor": "Pluripotent Stem Cells", "descriptor_ui": "D039904", "major_topic": false }, { "descriptor": "Transcription Factors", "descriptor_ui": "D014157", "major_topic": false } ], "publication": { "conference_name": null, "date": "2015 Dec 25", "date_precision": "day", "issue": "52", "normalized_date": "2015-12-25", "pages": "31173-31188", "proceedings_title": null, "publisher": "", "title": "The Journal of biological chemistry", "volume": "290", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "Induction of Pluripotency in Astrocytes through a Neural Stem Cell-like State.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Direct observation of gas molecules confined in the nanospace of porous materials by single-crystal X-ray diffraction (SXRD) technique is significant because it leads to deep insight into the adsorption mechanism and the actual state of the adsorbents in molecular level. A recent study revealed that flexibility is one of the important factors to achieve periodic guest accommodation in the nanospace enabling direct observation of gas molecules. Here, we report a convenient strategy to tune the framework flexibility by just an atomic exchange in a ligand, which enables us to easily construct a soft nanospace as the best platform to study gas adsorption. Indeed, we succeeded to observe C2H2 and CO2 molecules confined in the pores of a flexible porous coordination polymer (PCP-N) in different configurations using SXRD measurement, whereas gas molecules in a rigid framework (PCP-C) isostructural to PCP-N were not seen crystallographically. The result of the coincident in situ powder X-ray diffraction and adsorption measurement for PCP-N unambiguously showed that the framework could flexibly transform to trap gas molecules with a commensurate fashion. In addition, for PCP-N, we found that the adsorbed gas molecules induced significant structural change involving dimensional change of the pore from one-dimensional to three-dimensional, and subsequently, additional gas molecules formed periodic molecular clusters in the nanospace.", "classifications": [ { "id": "Hijikata", "label": "Group Hijikata", "parent": "Tsuchiya", "type": "group" }, { "id": "Tsuchiya", "label": "Team Tsuchiya", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yunsheng", "last_name": "Ma", "name": null }, { "creator_type": "author", "first_name": "Ryotaro", "last_name": "Matsuda", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Yuh", "last_name": "Hijikata", "name": null }, { "creator_type": "author", "first_name": "Liangchun", "last_name": "Li", "name": null }, { "creator_type": "author", "first_name": "Shinpei", "last_name": "Kusaka", "name": null }, { "creator_type": "author", "first_name": "Mawlin", "last_name": "Foo", "name": null }, { "creator_type": "author", "first_name": "Fengfeng", "last_name": "Xue", "name": null }, { "creator_type": "author", "first_name": "George", "last_name": "Akiyama", "name": null }, { "creator_type": "author", "first_name": "Rongxin", "last_name": "Yuan", "name": null }, { "creator_type": "author", "first_name": "Susumu", "last_name": "Kitagawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/jacs.5b09666" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "26592095" } }, "mesh": [], "publication": { "conference_name": null, "date": "2015 Dec 23", "date_precision": "day", "issue": "50", "normalized_date": "2015-12-23", "pages": "15825-15832", "proceedings_title": null, "publisher": "", "title": "Journal of the American Chemical Society", "volume": "137", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "A Convenient Strategy for Designing a Soft Nanospace: An Atomic Exchange in a Ligand with Isostructural Frameworks.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Recent reports indicate the ubiquitous prevalence of hydropersulfides (RSSH) in mammalian systems. The biological utility of these and related species is currently a matter of significant speculation. The function, lifetime and fate of hydropersulfides will be assuredly based on their chemical properties and reactivity. Thus, to serve as the basis for further mechanistic studies regarding hydropersulfide biology, some of the basic chemical properties/reactivity of hydropersulfides was studied. The nucleophilicity, electrophilicity and redox properties of hydropersulfides were examined under biological conditions. These studies indicate that hydropersulfides can be nucleophilic or electrophilic, depending on the pH (i.e. the protonation state) and can act as good one- and two-electron reductants. These diverse chemical properties in a single species make hydropersulfides chemically distinct from other, well-known sulfur containing biological species, giving them unique and potentially important biological function.", "classifications": [ { "id": "Akaike", "label": "Group Akaike", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Simran S.", "last_name": "Saund", "name": null }, { "creator_type": "author", "first_name": "Victor", "last_name": "Sosa", "name": null }, { "creator_type": "author", "first_name": "Stephanie", "last_name": "Henriquez", "name": null }, { "creator_type": "author", "first_name": "Q. Nhu N.", "last_name": "Nguyen", "name": null }, { "creator_type": "author", "first_name": "Christopher L.", "last_name": "Bianco", "name": null }, { "creator_type": "author", "first_name": "Shuhei", "last_name": "Soeda", "name": null }, { "creator_type": "author", "first_name": "Robert", "last_name": "Millikin", "name": null }, { "creator_type": "author", "first_name": "Corey", "last_name": "White", "name": null }, { "creator_type": "author", "first_name": "Henry", "last_name": "Le", "name": null }, { "creator_type": "author", "first_name": "Katsuhiko", "last_name": "Ono", "name": null }, { "creator_type": "author", "first_name": "Dean J.", "last_name": "Tantillo", "name": null }, { "creator_type": "author", "first_name": "Yoshito", "last_name": "Kumagai", "name": null }, { "creator_type": "author", "first_name": "Takaaki", "last_name": "Akaike", "name": null }, { "creator_type": "author", "first_name": "Joseph", "last_name": "Lin", "name": null }, { "creator_type": "author", "first_name": "Jon M.", "last_name": "Fukuto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.abb.2015.10.016" }, "pmcid": { "normalized": "PMC4833115" }, "pmid": { "normalized": "26519887" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cyanides", "descriptor_ui": "D003486", "major_topic": false }, { "descriptor": "Cystathionine gamma-Lyase", "descriptor_ui": "D003542", "major_topic": false }, { "descriptor": "Glutathione", "descriptor_ui": "D005978", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Magnetic Resonance Spectroscopy", "descriptor_ui": "D009682", "major_topic": false }, { "descriptor": "Models, Chemical", "descriptor_ui": "D008956", "major_topic": false }, { "descriptor": "Oxidation-Reduction", "descriptor_ui": "D010084", "major_topic": false }, { "descriptor": "Peptide Fragments", "descriptor_ui": "D010446", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Receptor-Like Protein Tyrosine Phosphatases, Class 3", "descriptor_ui": "D054631", "major_topic": false }, { "descriptor": "Recombinant Proteins", "descriptor_ui": "D011994", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Sulfides", "descriptor_ui": "D013440", "major_topic": false } ], "publication": { "conference_name": null, "date": "2015 Dec 15", "date_precision": "day", "issue": "", "normalized_date": "2015-12-15", "pages": "15-24", "proceedings_title": null, "publisher": "", "title": "Archives of biochemistry and biophysics", "volume": "588", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "The chemical biology of hydropersulfides (RSSH): Chemical stability, reactivity and redox roles.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Understanding the mechanisms regulating development requires a quantitative characterization of cell divisions, rearrangements, cell size and shape changes, and apoptoses. We developed a multiscale formalism that relates the characterizations of each cell process to tissue growth and morphogenesis. Having validated the formalism on computer simulations, we quantified separately all morphogenetic events in the Drosophila dorsal thorax and wing pupal epithelia to obtain comprehensive statistical maps linking cell and tissue scale dynamics. While globally cell shape changes, rearrangements and divisions all significantly participate in tissue morphogenesis, locally, their relative participations display major variations in space and time. By blocking division we analyzed the impact of division on rearrangements, cell shape changes and tissue morphogenesis. Finally, by combining the formalism with mechanical stress measurement, we evidenced unexpected interplays between patterns of tissue elongation, cell division and stress. Our formalism provides a novel and rigorous approach to uncover mechanisms governing tissue development.", "classifications": [ { "id": "Ishihara", "label": "Group Ishihara", "parent": "Sawai", "type": "group" }, { "id": "Sawai", "label": "Team Sawai", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Boris", "last_name": "Guirao", "name": null }, { "creator_type": "author", "first_name": "Stéphane U.", "last_name": "Rigaud", "name": null }, { "creator_type": "author", "first_name": "Floris", "last_name": "Bosveld", "name": null }, { "creator_type": "author", "first_name": "Anaïs", "last_name": "Bailles", "name": null }, { "creator_type": "author", "first_name": "Jesús", "last_name": "López-Gay", "name": null }, { "creator_type": "author", "first_name": "Shuji", "last_name": "Ishihara", "name": null }, { "creator_type": "author", "first_name": "Kaoru", "last_name": "Sugimura", "name": null }, { "creator_type": "author", "first_name": "François", "last_name": "Graner", "name": null }, { "creator_type": "author", "first_name": "Yohanns", "last_name": "Bellaïche", "name": null } ], "identifiers": { "doi": { "normalized": "10.7554/elife.08519" }, "pmcid": { "normalized": "PMC4811803" }, "pmid": { "normalized": "26653285" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Computer Simulation", "descriptor_ui": "D003198", "major_topic": false }, { "descriptor": "Drosophila", "descriptor_ui": "D004330", "major_topic": false }, { "descriptor": "Epithelium", "descriptor_ui": "D004848", "major_topic": false }, { "descriptor": "Models, Biological", "descriptor_ui": "D008954", "major_topic": true } ], "publication": { "conference_name": null, "date": "2015 Dec 12", "date_precision": "day", "issue": "", "normalized_date": "2015-12-12", "pages": "e08519", "proceedings_title": null, "publisher": "", "title": "eLife", "volume": "4", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "Unified quantitative characterization of epithelial tissue development.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The development of stimulated emission depletion (STED) microscopy represented a major breakthrough in cellular and molecular biology. However, the intense laser beams required for both excitation and STED usually provoke rapid photobleaching of fluorescent molecular probes, which significantly limits the performance and practical utility of STED microscopy. We herein developed a photoresistant fluorescent dye C-Naphox as a practical tool for STED imaging. With excitation using either a lambda=405 or 488 nm laser in protic solvents, C-Naphox exhibited an intense red/orange fluorescence (quantum yield PhiF >0.7) with a large Stokes shift (circa 5900 cm(-1) ). Even after irradiation with a Xe lamp (300 W, lambdaex =460 nm, full width at half maximum (FWHM)=11 nm) for 12 hours, 99.5 % of C-Naphox remained intact. The high photoresistance of C-Naphox allowed repeated STED imaging of HeLa cells. Even after recording 50 STED images, 83 % of the initial fluorescence intensity persisted.", "classifications": [ { "id": "Sato", "label": "Group Sato", "parent": "Tsuchiya", "type": "group" }, { "id": "Tsuchiya", "label": "Team Tsuchiya", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Chenguang", "last_name": "Wang", "name": null }, { "creator_type": "author", "first_name": "Aiko", "last_name": "Fukazawa", "name": null }, { "creator_type": "author", "first_name": "Masayasu", "last_name": "Taki", "name": null }, { "creator_type": "author", "first_name": "Yoshikatsu", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Tetsuya", "last_name": "Higashiyama", "name": null }, { "creator_type": "author", "first_name": "Shigehiro", "last_name": "Yamaguchi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/anie.201507939" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "26493944" } }, "mesh": [ { "descriptor": "Fluorescence", "descriptor_ui": "D005453", "major_topic": false }, { "descriptor": "Fluorescent Dyes", "descriptor_ui": "D005456", "major_topic": false }, { "descriptor": "HeLa Cells", "descriptor_ui": "D006367", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Lasers", "descriptor_ui": "D007834", "major_topic": false }, { "descriptor": "Microscopy, Fluorescence", "descriptor_ui": "D008856", "major_topic": false }, { "descriptor": "Phosphorus Compounds", "descriptor_ui": "D017553", "major_topic": false }, { "descriptor": "Photobleaching", "descriptor_ui": "D038761", "major_topic": true } ], "publication": { "conference_name": null, "date": "2015 Dec 7", "date_precision": "day", "issue": "50", "normalized_date": "2015-12-07", "pages": "15213-15217", "proceedings_title": null, "publisher": "", "title": "Angewandte Chemie (International ed. in English)", "volume": "54", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "A Phosphole Oxide Based Fluorescent Dye with Exceptional Resistance to Photobleaching: A Practical Tool for Continuous Imaging in STED Microscopy.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Phenotype switching with and without sensing environment is a common strategy of organisms to survive in a fluctuating environment. Understanding the evolutionary advantages of switching and sensing requires a quantitative evaluation of their fitness gain and its fluctuation together with the conditions for the switching and sensing strategies being adapted to a given environment. In this work, by using a pathwise formulation of the population dynamics, we show that the optimal switching strategy is characterized by a consistency condition for time-forward and backward path probabilities. The formulation also clarifies the underlying information-theoretic aspect of selection as a passive information compression. The loss of fitness by a suboptimal strategy is also shown to satisfy a fluctuation relation, which provides us with the information on how environmental fluctuation impacts the advantages of the optimal strategy. These results are naturally extended to the situation that organisms can use an environmental signal by actively sensing the environment. The fluctuation relations of the fitness gain by sensing are derived in which the multivariate mutual information among the phenotype, the environment, and the signal plays the role to quantify the relevant information in the signal for the fitness gain.", "classifications": [ { "id": "Kobayashi", "label": "Group Kobayashi", "parent": "Wakamoto", "type": "group" }, { "id": "Wakamoto", "label": "Team Wakamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Tetsuya J.", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Sughiyama", "name": null } ], "identifiers": { "doi": { "normalized": "10.1103/physrevlett.115.238102" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "26684143" } }, "mesh": [], "publication": { "conference_name": null, "date": "2015 Dec 4", "date_precision": "day", "issue": "23", "normalized_date": "2015-12-04", "pages": "238102", "proceedings_title": null, "publisher": "", "title": "Physical review letters", "volume": "115", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "Fluctuation Relations of Fitness and Information in Population Dynamics.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Imaging techniques for visualizing and analyzing precise morphology and gene expression patterns are essential for understanding biological processes during development in all organisms. With the aid of chemical screening, we developed a clearing method using chemical solutions, termed ClearSee, for deep imaging of morphology and gene expression in plant tissues. ClearSee rapidly diminishes chlorophyll autofluorescence while maintaining fluorescent protein stability. By adjusting the refractive index mismatch, whole-organ and whole-plant imaging can be performed by both confocal and two-photon excitation microscopy in ClearSee-treated samples. Moreover, ClearSee is applicable to multicolor imaging of fluorescent proteins to allow structural analysis of multiple gene expression. Given that ClearSee is compatible with staining by chemical dyes, the technique is useful for deep imaging in conjunction with genetic markers and for plant species not amenable to transgenic approaches. This method is useful for whole imaging for intact morphology and will help to accelerate the discovery of new phenomena in plant biological research.", "classifications": [ { "id": "Sato", "label": "Group Sato", "parent": "Tsuchiya", "type": "group" }, { "id": "Tsuchiya", "label": "Team Tsuchiya", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Daisuke", "last_name": "Kurihara", "name": null }, { "creator_type": "author", "first_name": "Yoko", "last_name": "Mizuta", "name": null }, { "creator_type": "author", "first_name": "Yoshikatsu", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Tetsuya", "last_name": "Higashiyama", "name": null } ], "identifiers": { "doi": { "normalized": "10.1242/dev.127613" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "26493404" } }, "mesh": [ { "descriptor": "Arabidopsis", "descriptor_ui": "D017360", "major_topic": false }, { "descriptor": "Chlorophyll", "descriptor_ui": "D002734", "major_topic": false }, { "descriptor": "Cloning, Molecular", "descriptor_ui": "D003001", "major_topic": false }, { "descriptor": "Fluorescence", "descriptor_ui": "D005453", "major_topic": false }, { "descriptor": "Fluorescent Dyes", "descriptor_ui": "D005456", "major_topic": false }, { "descriptor": "Green Fluorescent Proteins", "descriptor_ui": "D049452", "major_topic": false }, { "descriptor": "Indicators and Reagents", "descriptor_ui": "D007202", "major_topic": false }, { "descriptor": "Microscopy, Confocal", "descriptor_ui": "D018613", "major_topic": false }, { "descriptor": "Microscopy, Fluorescence", "descriptor_ui": "D008856", "major_topic": false }, { "descriptor": "Phloem", "descriptor_ui": "D052585", "major_topic": false }, { "descriptor": "Photons", "descriptor_ui": "D017785", "major_topic": false }, { "descriptor": "Plant Leaves", "descriptor_ui": "D018515", "major_topic": false }, { "descriptor": "Plant Roots", "descriptor_ui": "D018517", "major_topic": false }, { "descriptor": "Plants", "descriptor_ui": "D010944", "major_topic": false }, { "descriptor": "Plants, Genetically Modified", "descriptor_ui": "D030821", "major_topic": false }, { "descriptor": "Urea", "descriptor_ui": "D014508", "major_topic": false }, { "descriptor": "Xylitol", "descriptor_ui": "D014993", "major_topic": false } ], "publication": { "conference_name": null, "date": "2015 Dec 1", "date_precision": "day", "issue": "23", "normalized_date": "2015-12-01", "pages": "4168-4179", "proceedings_title": null, "publisher": "", "title": "Development (Cambridge, England)", "volume": "142", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "ClearSee: a rapid optical clearing reagent for whole-plant fluorescence imaging.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Broad clinical interest rapidly followed the recent discovery of different subpopulations of T cells that have immune regulatory properties and a number of studies have been conducted aiming to dissect the translational potential of these promising cells. In this review we will focus on forkhead box P3 (FoxP3) positive regulatory T cells, T regulatory type 1 cells and invariant natural killer T cells (iNKT). We will analyze their ability to correct immune dysregulation in animal models of immune mediated diseases and we will examine the first clinical approaches where these cells have been directly or indirectly employed. We will discuss successes, challenges and limitations that rose in the road to the clinical use of regulatory T cells.", "classifications": [ { "id": "Nishikii", "label": "Group Nishikii", "parent": "Shintaku", "type": "group" }, { "id": "Shintaku", "label": "Team Shintaku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Antonio", "last_name": "Pierini", "name": null }, { "creator_type": "author", "first_name": "Dominik", "last_name": "Schneidawind", "name": null }, { "creator_type": "author", "first_name": "Hidekazu", "last_name": "Nishikii", "name": null }, { "creator_type": "author", "first_name": "Robert S.", "last_name": "Negrin", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/s40778-015-0025-1" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "26779417" } }, "mesh": [], "publication": { "conference_name": null, "date": "2015 Dec 1", "date_precision": "day", "issue": "4", "normalized_date": "2015-12-01", "pages": "177-186", "proceedings_title": null, "publisher": "", "title": "Current stem cell reports", "volume": "1", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "Regulatory T Cell Immunotherapy in Immune-Mediated Diseases.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The developing dorsomedial telencephalon includes the medial pallium, which goes on to form the hippocampus. Generating a reliable source of human hippocampal tissue is an important step for cell-based research into hippocampus-related diseases. Here we show the generation of functional hippocampal granule- and pyramidal-like neurons from self-organizing dorsomedial telencephalic tissue using human embryonic stem cells (hESCs). First, we develop a hESC culture method that utilizes bone morphogenetic protein (BMP) and Wnt signalling to induce choroid plexus, the most dorsomedial portion of the telencephalon. Then, we find that titrating BMP and Wnt exposure allowed the self-organization of medial pallium tissues. Following long-term dissociation culture, these dorsomedial telencephalic tissues give rise to Zbtb20(+)/Prox1(+) granule neurons and Zbtb20(+)/KA1(+) pyramidal neurons, both of which were electrically functional with network formation. Thus, we have developed an in vitro model that recapitulates human hippocampus development, allowing the generation of functional hippocampal granule- and pyramidal-like neurons.", "classifications": [ { "id": "Eiraku", "label": "Group Eiraku", "parent": "Eiraku", "type": "group" }, { "id": "Eiraku", "label": "Team Eiraku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Hideya", "last_name": "Sakaguchi", "name": null }, { "creator_type": "author", "first_name": "Taisuke", "last_name": "Kadoshima", "name": null }, { "creator_type": "author", "first_name": "Mika", "last_name": "Soen", "name": null }, { "creator_type": "author", "first_name": "Nobuhiro", "last_name": "Narii", "name": null }, { "creator_type": "author", "first_name": "Yoshihito", "last_name": "Ishida", "name": null }, { "creator_type": "author", "first_name": "Masatoshi", "last_name": "Ohgushi", "name": null }, { "creator_type": "author", "first_name": "Jun", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Mototsugu", "last_name": "Eiraku", "name": null }, { "creator_type": "author", "first_name": "Yoshiki", "last_name": "Sasai", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/ncomms9896" }, "pmcid": { "normalized": "PMC4660208" }, "pmid": { "normalized": "26573335" } }, "mesh": [ { "descriptor": "Bone Morphogenetic Proteins", "descriptor_ui": "D019485", "major_topic": false }, { "descriptor": "Cell Culture Techniques", "descriptor_ui": "D018929", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Choroid Plexus", "descriptor_ui": "D002831", "major_topic": false }, { "descriptor": "Hippocampus", "descriptor_ui": "D006624", "major_topic": false }, { "descriptor": "Human Embryonic Stem Cells", "descriptor_ui": "D000066449", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Immunohistochemistry", "descriptor_ui": "D007150", "major_topic": false }, { "descriptor": "In Vitro Techniques", "descriptor_ui": "D066298", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Patch-Clamp Techniques", "descriptor_ui": "D018408", "major_topic": false }, { "descriptor": "Polymerase Chain Reaction", "descriptor_ui": "D016133", "major_topic": false }, { "descriptor": "Pyramidal Cells", "descriptor_ui": "D017966", "major_topic": false }, { "descriptor": "Telencephalon", "descriptor_ui": "D013687", "major_topic": false }, { "descriptor": "Wnt Proteins", "descriptor_ui": "D051153", "major_topic": false }, { "descriptor": "Wnt Signaling Pathway", "descriptor_ui": "D060449", "major_topic": false } ], "publication": { "conference_name": null, "date": "2015 Nov 17", "date_precision": "day", "issue": "", "normalized_date": "2015-11-17", "pages": "8896", "proceedings_title": null, "publisher": "", "title": "Nature communications", "volume": "6", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "Generation of functional hippocampal neurons from self-organizing human embryonic stem cell-derived dorsomedial telencephalic tissue.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Endogenous hydrogen polysulfides (H2Sn; n>1) have been recognized as important regulators in sulfur-related redox biology. H2Sn can activate tumor suppressors, ion channels, and transcription factors with higher potency than H2S. Although H2Sn are drawing increasing attention, their exact mechanisms of action are still poorly understood. A major hurdle in this field is the lack of reliable and convenient methods for H2Sn detection. Herein we report a H2Sn-mediated benzodithiolone formation under mild conditions. This method takes advantage of the unique dual reactivity of H2Sn as both a nucleophile and an electrophile. Based on this reaction, three fluorescent probes (PSP-1, PSP-2, and PSP-3) were synthesized and evaluated. Among the probes prepared, PSP-3 showed a desirable off/on fluorescence response to H2Sn and high specificity. The probe was successfully applied in visualizing intracellular H2Sn.", "classifications": [ { "id": "Akaike", "label": "Group Akaike", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Wei", "last_name": "Chen", "name": null }, { "creator_type": "author", "first_name": "Ethan W.", "last_name": "Rosser", "name": null }, { "creator_type": "author", "first_name": "Tetsuro", "last_name": "Matsunaga", "name": null }, { "creator_type": "author", "first_name": "Armando", "last_name": "Pacheco", "name": null }, { "creator_type": "author", "first_name": "Takaaki", "last_name": "Akaike", "name": null }, { "creator_type": "author", "first_name": "Ming", "last_name": "Xian", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/anie.201506887" }, "pmcid": { "normalized": "PMC4715616" }, "pmid": { "normalized": "26381762" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "Chlorocebus aethiops", "descriptor_ui": "D002522", "major_topic": false }, { "descriptor": "Fluorescence", "descriptor_ui": "D005453", "major_topic": false }, { "descriptor": "Fluorescent Dyes", "descriptor_ui": "D005456", "major_topic": false }, { "descriptor": "HeLa Cells", "descriptor_ui": "D006367", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Hydrogen", "descriptor_ui": "D006859", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Molecular Structure", "descriptor_ui": "D015394", "major_topic": false }, { "descriptor": "Sulfides", "descriptor_ui": "D013440", "major_topic": false }, { "descriptor": "Vero Cells", "descriptor_ui": "D014709", "major_topic": false } ], "publication": { "conference_name": null, "date": "2015 Nov 16", "date_precision": "day", "issue": "47", "normalized_date": "2015-11-16", "pages": "13961-13965", "proceedings_title": null, "publisher": "", "title": "Angewandte Chemie (International ed. in English)", "volume": "54", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "The Development of Fluorescent Probes for Visualizing Intracellular Hydrogen Polysulfides.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: Hydrogen sulfide (H2S) exhibits protective effects in various disease models including cerebral ischemia-reperfusion (I/R) injury. Nonetheless, mechanisms and identity of molecules responsible for neuroprotective effects of H2S remain incompletely defined. In the current study, we observed that thiosulfate, an oxidation product of H2S, mediates protective effects of an H2S donor compound sodium sulfide (Na2S) against neuronal I/R injury. METHODS AND RESULTS: We observed that thiosulfate in cell culture medium is not only required but also sufficient to mediate cytoprotective effects of Na2S against oxygen glucose deprivation and reoxygenation of human neuroblastoma cell line (SH-SY5Y) and murine primary cortical neurons. Systemic administration of sodium thiosulfate (STS) improved survival and neurological function of mice subjected to global cerebral I/R injury. Beneficial effects of STS, as well as Na2S, were associated with marked increase of thiosulfate, but not H2S, in plasma and brain tissues. These results suggest that thiosulfate is a circulating \"carrier\" molecule of beneficial effects of H2S. Protective effects of thiosulfate were associated with inhibition of caspase-3 activity by persulfidation at Cys163 in caspase-3. We discovered that an SLC13 family protein, sodium sulfate cotransporter 2 (SLC13A4, NaS-2), facilitates transport of thiosulfate, but not sulfide, across the cell membrane, regulating intracellular concentrations and thus mediating cytoprotective effects of Na2S and STS. CONCLUSIONS: The protective effects of H2S are mediated by thiosulfate that is transported across cell membrane by NaS-2 and exerts antiapoptotic effects via persulfidation of caspase-3. Given the established safety track record, thiosulfate may be therapeutic against ischemic brain injury.", "classifications": [ { "id": "Akaike", "label": "Group Akaike", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Eizo", "last_name": "Marutani", "name": null }, { "creator_type": "author", "first_name": "Marina", "last_name": "Yamada", "name": null }, { "creator_type": "author", "first_name": "Tomoaki", "last_name": "Ida", "name": null }, { "creator_type": "author", "first_name": "Kentaro", "last_name": "Tokuda", "name": null }, { "creator_type": "author", "first_name": "Kohei", "last_name": "Ikeda", "name": null }, { "creator_type": "author", "first_name": "Shinichi", "last_name": "Kai", "name": null }, { "creator_type": "author", "first_name": "Kazuhiro", "last_name": "Shirozu", "name": null }, { "creator_type": "author", "first_name": "Kei", "last_name": "Hayashida", "name": null }, { "creator_type": "author", "first_name": "Shizuko", "last_name": "Kosugi", "name": null }, { "creator_type": "author", "first_name": "Kenjiro", "last_name": "Hanaoka", "name": null }, { "creator_type": "author", "first_name": "Masao", "last_name": "Kaneki", "name": null }, { "creator_type": "author", "first_name": "Takaaki", "last_name": "Akaike", "name": null }, { "creator_type": "author", "first_name": "Fumito", "last_name": "Ichinose", "name": null } ], "identifiers": { "doi": { "normalized": "10.1161/jaha.115.002125" }, "pmcid": { "normalized": "PMC4845224" }, "pmid": { "normalized": "26546573" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Anion Transport Proteins", "descriptor_ui": "D027321", "major_topic": false }, { "descriptor": "Apoptosis", "descriptor_ui": "D017209", "major_topic": false }, { "descriptor": "Brain Ischemia", "descriptor_ui": "D002545", "major_topic": false }, { "descriptor": "Caspase 3", "descriptor_ui": "D053148", "major_topic": false }, { "descriptor": "Cell Hypoxia", "descriptor_ui": "D015687", "major_topic": false }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Cytoprotection", "descriptor_ui": "D019610", "major_topic": false }, { "descriptor": "Dose-Response Relationship, Drug", "descriptor_ui": "D004305", "major_topic": false }, { "descriptor": "Gestational Age", "descriptor_ui": "D005865", "major_topic": false }, { "descriptor": "Glucose", "descriptor_ui": "D005947", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mitochondria", "descriptor_ui": "D008928", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Neuroprotective Agents", "descriptor_ui": "D018696", "major_topic": false }, { "descriptor": "Oxidation-Reduction", "descriptor_ui": "D010084", "major_topic": false }, { "descriptor": "Reperfusion Injury", "descriptor_ui": "D015427", "major_topic": false }, { "descriptor": "Sulfate Transporters", "descriptor_ui": "D000076988", "major_topic": false }, { "descriptor": "Sulfites", "descriptor_ui": "D013447", "major_topic": false }, { "descriptor": "Symporters", "descriptor_ui": "D027981", "major_topic": false }, { "descriptor": "Thiosulfates", "descriptor_ui": "D013885", "major_topic": false }, { "descriptor": "Time Factors", "descriptor_ui": "D013997", "major_topic": false } ], "publication": { "conference_name": null, "date": "2015 Nov 6", "date_precision": "day", "issue": "11", "normalized_date": "2015-11-06", "pages": "", "proceedings_title": null, "publisher": "", "title": "Journal of the American Heart Association", "volume": "4", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "Thiosulfate Mediates Cytoprotective Effects of Hydrogen Sulfide Against Neuronal Ischemia.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Hyperuricaemia is an undisputed and highly predictive biomarker for cardiovascular risk. SLC17A1, expressed in the liver and kidneys, harbours potent candidate single nucleotide polymorphisms that decrease uric acid levels. Therefore, we examined SLC17A1 polymorphisms (rs1165196, rs1179086, and rs3757131), which might suppress cardiovascular risk factors and that are involved in liver functioning, via a large-scale pooled analysis of the Japanese general population in a cross-sectional study. Using data from the Japan Multi-Institutional Collaborative Cohort Study, we identified 1842 participants of both sexes, 35-69-years-old, having the requisite data, and analysed their SLC17A1 genotypes. In men, logistic regression analyses revealed that minor alleles in SLC17A1 polymorphisms (rs1165196 and rs3757131) were associated with a low-/high-density lipoprotein cholesterol ratio >2.0 (rs1165196: odds ratio [OR], 0.703; 95% confidence interval [CI], 0.536-0.922; rs3757131: OR, 0.658; 95% CI, 0.500-0.866), and with homocysteine levels of >10.0 nmol/mL (rs1165196: OR, 0.544; 95% CI, 0.374-0.792; rs3757131: OR, 0.509; 95% CI, 0.347-0.746). Therefore, these polymorphisms had dominant negative effects on cholesterol homeostasis and hyperhomocysteinaemia, in men, independent of alcohol consumption, physical activity, or daily energy and nutrition intake. Thus, genetic variants of SLC17A1 are potential biomarkers for altered cholesterol homeostasis and hyperhomocysteinaemia in Japanese men.", "classifications": [ { "id": "Tanaka", "label": "Group Tanaka", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Teruhide", "last_name": "Koyama", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Matsui", "name": null }, { "creator_type": "author", "first_name": "Nagato", "last_name": "Kuriyama", "name": null }, { "creator_type": "author", "first_name": "Etsuko", "last_name": "Ozaki", "name": null }, { "creator_type": "author", "first_name": "Keitaro", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Isao", "last_name": "Oze", "name": null }, { "creator_type": "author", "first_name": "Nobuyuki", "last_name": "Hamajima", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Wakai", "name": null }, { "creator_type": "author", "first_name": "Rieko", "last_name": "Okada", "name": null }, { "creator_type": "author", "first_name": "Kokichi", "last_name": "Arisawa", "name": null }, { "creator_type": "author", "first_name": "Haruo", "last_name": "Mikami", "name": null }, { "creator_type": "author", "first_name": "Keiichi", "last_name": "Shimatani", "name": null }, { "creator_type": "author", "first_name": "Akie", "last_name": "Hirata", "name": null }, { "creator_type": "author", "first_name": "Naoyuki", "last_name": "Takashima", "name": null }, { "creator_type": "author", "first_name": "Sadao", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Chisato", "last_name": "Nagata", "name": null }, { "creator_type": "author", "first_name": "Michiaki", "last_name": "Kubo", "name": null }, { "creator_type": "author", "first_name": "Hideo", "last_name": "Tanaka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/srep15888" }, "pmcid": { "normalized": "PMC4630628" }, "pmid": { "normalized": "26524967" } }, "mesh": [ { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Asian People", "descriptor_ui": "D044466", "major_topic": false }, { "descriptor": "Cholesterol", "descriptor_ui": "D002784", "major_topic": false }, { "descriptor": "Cholesterol, HDL", "descriptor_ui": "D008076", "major_topic": false }, { "descriptor": "Cholesterol, LDL", "descriptor_ui": "D008078", "major_topic": false }, { "descriptor": "Cohort Studies", "descriptor_ui": "D015331", "major_topic": false }, { "descriptor": "Cross-Sectional Studies", "descriptor_ui": "D003430", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Gene Frequency", "descriptor_ui": "D005787", "major_topic": false }, { "descriptor": "Genetic Predisposition to Disease", "descriptor_ui": "D020022", "major_topic": false }, { "descriptor": "Genotype", "descriptor_ui": "D005838", "major_topic": false }, { "descriptor": "Homeostasis", "descriptor_ui": "D006706", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Hyperhomocysteinemia", "descriptor_ui": "D020138", "major_topic": false }, { "descriptor": "Japan", "descriptor_ui": "D007564", "major_topic": false }, { "descriptor": "Logistic Models", "descriptor_ui": "D016015", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Polymorphism, Single Nucleotide", "descriptor_ui": "D020641", "major_topic": true }, { "descriptor": "Risk Factors", "descriptor_ui": "D012307", "major_topic": false }, { "descriptor": "Sex Factors", "descriptor_ui": "D012737", "major_topic": false }, { "descriptor": "Sodium-Phosphate Cotransporter Proteins, Type I", "descriptor_ui": "D050609", "major_topic": false } ], "publication": { "conference_name": null, "date": "2015 Nov 3", "date_precision": "day", "issue": "", "normalized_date": "2015-11-03", "pages": "15888", "proceedings_title": null, "publisher": "", "title": "Scientific reports", "volume": "5", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "Genetic variants of SLC17A1 are associated with cholesterol homeostasis and hyperhomocysteinaemia in Japanese men.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Nitrated guanine nucleotide 8-nitroguanosine 3',5'-cyclic monophosphate (8-nitro-cGMP) generated by reactive oxygen/nitrogen species causes protein S-guanylation. However, the mechanism of 8-nitro-cGMP formation and its protein targets in the normal brain have not been identified. Here, we investigated 8-nitro-cGMP generation and protein S-guanylation in the rodent brain. Immunohistochemistry indicated that 8-nitro-cGMP was produced by neurons, such as pyramidal cells and interneurons. Using liquid chromatography-tandem mass spectrometry, we determined endogenous 8-nitro-cGMP levels in the brain as 2.92 +/- 0.10 pmol/mg protein. Based on S-guanylation proteomics, we identified several S-guanylated neuronal proteins, including SNAP25 which is a core member of the soluble N-ethylmaleimide sensitive factor attachment protein receptor (SNARE) complex. SNAP25 post-translational modification including palmitoylation, phosphorylation, and oxidation, are known to regulate neurotransmission. Our results demonstrate that S-guanylation of SNAP25 enhanced the stability of the SNARE complex, which was further promoted by Ca(2+)-dependent activation of neuronal nitric oxide synthase. Using site-directed mutagenesis, we identified SNAP25 cysteine 90 as the main target of S-guanylation which enhanced the stability of the SNARE complex. The present study revealed a novel target of redox signaling via protein S-guanylation in the nervous system and provided the first substantial evidence of 8-nitro-cGMP function in the nervous system.", "classifications": [ { "id": "Akaike", "label": "Group Akaike", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Kohei", "last_name": "Kunieda", "name": null }, { "creator_type": "author", "first_name": "Hiroyasu", "last_name": "Tsutsuki", "name": null }, { "creator_type": "author", "first_name": "Tomoaki", "last_name": "Ida", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Kishimoto", "name": null }, { "creator_type": "author", "first_name": "Shingo", "last_name": "Kasamatsu", "name": null }, { "creator_type": "author", "first_name": "Tomohiro", "last_name": "Sawa", "name": null }, { "creator_type": "author", "first_name": "Naoki", "last_name": "Goshima", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Itakura", "name": null }, { "creator_type": "author", "first_name": "Masami", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Takaaki", "last_name": "Akaike", "name": null }, { "creator_type": "author", "first_name": "Hideshi", "last_name": "Ihara", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/acschemneuro.5b00196" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "26221773" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Brain", "descriptor_ui": "D001921", "major_topic": false }, { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "Cyclic GMP", "descriptor_ui": "D006152", "major_topic": false }, { "descriptor": "Cysteine", "descriptor_ui": "D003545", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mutagenesis, Site-Directed", "descriptor_ui": "D016297", "major_topic": false }, { "descriptor": "Neuroblastoma", "descriptor_ui": "D009447", "major_topic": false }, { "descriptor": "Nitric Oxide Synthase Type I", "descriptor_ui": "D052248", "major_topic": false }, { "descriptor": "Protein Processing, Post-Translational", "descriptor_ui": "D011499", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Rats, Wistar", "descriptor_ui": "D017208", "major_topic": false }, { "descriptor": "Reactive Oxygen Species", "descriptor_ui": "D017382", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "SNARE Proteins", "descriptor_ui": "D050600", "major_topic": false }, { "descriptor": "Synaptosomal-Associated Protein 25", "descriptor_ui": "D050825", "major_topic": false }, { "descriptor": "Synaptosomes", "descriptor_ui": "D013574", "major_topic": false } ], "publication": { "conference_name": null, "date": "2015 Oct 21", "date_precision": "day", "issue": "10", "normalized_date": "2015-10-21", "pages": "1715-1725", "proceedings_title": null, "publisher": "", "title": "ACS chemical neuroscience", "volume": "6", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "8-Nitro-cGMP Enhances SNARE Complex Formation through S-Guanylation of Cys90 in SNAP25.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The role of secreted molecules in cellular reprogramming has been poorly understood. Here we identify a truncated form of ephrin receptor A7 (EPHA7) as a key regulator of reprogramming. Truncated EPHA7 is prominently upregulated and secreted during reprogramming. EPHA7 expression is directly regulated by OCT3/4. EphA7 knockdown results in marked reduction of reprogramming efficiency, and the addition of truncated EPHA7 is able to restore it. ERK activity is markedly reduced during reprogramming, and the secreted, truncated EPHA7 is responsible for ERK activity reduction. Remarkably, treatment of EphA7-knockdown MEFs with the ERK pathway inhibitor restores reprogramming efficiency. Analyses show that truncated EPHA7-induced ERK activity reduction plays an important role in the middle phase of reprogramming. Thus, our findings uncover the importance of secreted EPHA7-induced ERK activity reduction in reprogramming.", "classifications": [ { "id": "Yamamoto", "label": "Group Yamamoto", "parent": "Toyoshima", "type": "group" }, { "id": "Toyoshima", "label": "Team Toyoshima", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Joonseong", "last_name": "Lee", "name": null }, { "creator_type": "author", "first_name": "May", "last_name": "Nakajima-Koyama", "name": null }, { "creator_type": "author", "first_name": "Masamitsu", "last_name": "Sone", "name": null }, { "creator_type": "author", "first_name": "Makito", "last_name": "Koga", "name": null }, { "creator_type": "author", "first_name": "Miki", "last_name": "Ebisuya", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Eisuke", "last_name": "Nishida", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.stemcr.2015.09.001" }, "pmcid": { "normalized": "PMC4625027" }, "pmid": { "normalized": "26441306" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Cellular Reprogramming", "descriptor_ui": "D065150", "major_topic": true }, { "descriptor": "Fibroblasts", "descriptor_ui": "D005347", "major_topic": false }, { "descriptor": "Gene Knockdown Techniques", "descriptor_ui": "D055785", "major_topic": false }, { "descriptor": "HEK293 Cells", "descriptor_ui": "D057809", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "MAP Kinase Signaling System", "descriptor_ui": "D020935", "major_topic": true }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred ICR", "descriptor_ui": "D008813", "major_topic": false }, { "descriptor": "Receptor, EphA7", "descriptor_ui": "D036141", "major_topic": false } ], "publication": { "conference_name": null, "date": "2015 Oct 13", "date_precision": "day", "issue": "4", "normalized_date": "2015-10-13", "pages": "480-489", "proceedings_title": null, "publisher": "", "title": "Stem cell reports", "volume": "5", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "Secreted Ephrin Receptor A7 Promotes Somatic Cell Reprogramming by Inducing ERK Activity Reduction.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Strigolactones are naturally occurring signaling molecules that affect plant development, fungi-plant interactions, and parasitic plant infestations. We characterized the function of 11 strigolactone receptors from the parasitic plant Striga hermonthica using chemical and structural biology. We found a clade of polyspecific receptors, including one that is sensitive to picomolar concentrations of strigolactone. A crystal structure of a highly sensitive strigolactone receptor from Striga revealed a larger binding pocket than that of the Arabidopsis receptor, which could explain the increased range of strigolactone sensitivity. Thus, the sensitivity of Striga to strigolactones from host plants is driven by receptor sensitivity. By expressing strigolactone receptors in Arabidopsis, we developed a bioassay that can be used to identify chemicals and crops with altered strigolactone levels.", "classifications": [ { "id": "Tsuchiya", "label": "Group Tsuchiya", "parent": "Tsuchiya", "type": "group" }, { "id": "Tsuchiya", "label": "Team Tsuchiya", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Shigeo", "last_name": "Toh", "name": null }, { "creator_type": "author", "first_name": "Duncan", "last_name": "Holbrook-Smith", "name": null }, { "creator_type": "author", "first_name": "Peter J.", "last_name": "Stogios", "name": null }, { "creator_type": "author", "first_name": "Olena", "last_name": "Onopriyenko", "name": null }, { "creator_type": "author", "first_name": "Shelley", "last_name": "Lumba", "name": null }, { "creator_type": "author", "first_name": "Yuichiro", "last_name": "Tsuchiya", "name": null }, { "creator_type": "author", "first_name": "Alexei", "last_name": "Savchenko", "name": null }, { "creator_type": "author", "first_name": "Peter", "last_name": "McCourt", "name": null } ], "identifiers": { "doi": { "normalized": "10.1126/science.aac9476" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "26450211" } }, "mesh": [ { "descriptor": "Amino Acid Sequence", "descriptor_ui": "D000595", "major_topic": false }, { "descriptor": "Arabidopsis", "descriptor_ui": "D017360", "major_topic": false }, { "descriptor": "Catalytic Domain", "descriptor_ui": "D020134", "major_topic": false }, { "descriptor": "Germination", "descriptor_ui": "D018525", "major_topic": false }, { "descriptor": "Heterocyclic Compounds, 3-Ring", "descriptor_ui": "D006575", "major_topic": false }, { "descriptor": "Lactones", "descriptor_ui": "D007783", "major_topic": false }, { "descriptor": "Molecular Sequence Data", "descriptor_ui": "D008969", "major_topic": false }, { "descriptor": "Phylogeny", "descriptor_ui": "D010802", "major_topic": false }, { "descriptor": "Plant Growth Regulators", "descriptor_ui": "D010937", "major_topic": false }, { "descriptor": "Plant Proteins", "descriptor_ui": "D010940", "major_topic": false }, { "descriptor": "Protein Structure, Secondary", "descriptor_ui": "D017433", "major_topic": false }, { "descriptor": "Receptors, Cell Surface", "descriptor_ui": "D011956", "major_topic": false }, { "descriptor": "Seeds", "descriptor_ui": "D012639", "major_topic": false }, { "descriptor": "Striga", "descriptor_ui": "D034362", "major_topic": false }, { "descriptor": "Structure-Activity Relationship", "descriptor_ui": "D013329", "major_topic": false } ], "publication": { "conference_name": null, "date": "2015 Oct 9", "date_precision": "day", "issue": "6257", "normalized_date": "2015-10-09", "pages": "203-207", "proceedings_title": null, "publisher": "", "title": "Science (New York, N.Y.)", "volume": "350", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "Structure-function analysis identifies highly sensitive strigolactone receptors in Striga.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "In the neocortex, higher-order areas are essential to integrate sensory-motor information and have expanded in size during evolution. How higher-order areas are specified, however, remains largely unknown. Here, we show that the migration and distribution of early-born neurons, the Cajal-Retzius cells (CRs), controls the size of higher-order areas in the mouse somatosensory, auditory, and visual cortex. Using live imaging, genetics, and in silico modeling, we show that subtype-specific differences in the onset, speed, and directionality of CR migration determine their differential invasion of the developing cortical surface. CR migration speed is cell autonomously modulated by vesicle-associated membrane protein 3 (VAMP3), a classically non-neuronal mediator of endosomal recycling. Increasing CR migration speed alters their distribution in the developing cerebral cortex and leads to an expansion of postnatal higher-order areas and congruent rewiring of thalamo-cortical input. Our findings thus identify novel roles for neuronal migration and VAMP3-dependent vesicular trafficking in cortical wiring.", "classifications": [ { "id": "Morishita", "label": "Group Morishita", "parent": "Morishita", "type": "group" }, { "id": "Morishita", "label": "Team Morishita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Melissa", "last_name": "Barber", "name": null }, { "creator_type": "author", "first_name": "Yoko", "last_name": "Arai", "name": null }, { "creator_type": "author", "first_name": "Yoshihiro", "last_name": "Morishita", "name": null }, { "creator_type": "author", "first_name": "Lisa", "last_name": "Vigier", "name": null }, { "creator_type": "author", "first_name": "Frederic", "last_name": "Causeret", "name": null }, { "creator_type": "author", "first_name": "Ugo", "last_name": "Borello", "name": null }, { "creator_type": "author", "first_name": "Fanny", "last_name": "Ledonne", "name": null }, { "creator_type": "author", "first_name": "Eva", "last_name": "Coppola", "name": null }, { "creator_type": "author", "first_name": "Vincent", "last_name": "Contremoulins", "name": null }, { "creator_type": "author", "first_name": "Frank W.", "last_name": "Pfrieger", "name": null }, { "creator_type": "author", "first_name": "Fadel", "last_name": "Tissir", "name": null }, { "creator_type": "author", "first_name": "Subashika", "last_name": "Govindan", "name": null }, { "creator_type": "author", "first_name": "Denis", "last_name": "Jabaudon", "name": null }, { "creator_type": "author", "first_name": "Veronique", "last_name": "Proux-Gillardeaux", "name": null }, { "creator_type": "author", "first_name": "Thierry", "last_name": "Galli", "name": null }, { "creator_type": "author", "first_name": "Alessandra", "last_name": "Pierani", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.cub.2015.08.028" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "26387718" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Movement", "descriptor_ui": "D002465", "major_topic": false }, { "descriptor": "Cerebral Cortex", "descriptor_ui": "D002540", "major_topic": false }, { "descriptor": "Interstitial Cells of Cajal", "descriptor_ui": "D056885", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Transgenic", "descriptor_ui": "D008822", "major_topic": false }, { "descriptor": "Models, Biological", "descriptor_ui": "D008954", "major_topic": false }, { "descriptor": "Neocortex", "descriptor_ui": "D019579", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Vesicle-Associated Membrane Protein 3", "descriptor_ui": "D051040", "major_topic": false } ], "publication": { "conference_name": null, "date": "2015 Oct 5", "date_precision": "day", "issue": "19", "normalized_date": "2015-10-05", "pages": "2466-2478", "proceedings_title": null, "publisher": "", "title": "Current biology : CB", "volume": "25", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "Migration Speed of Cajal-Retzius Cells Modulated by Vesicular Trafficking Controls the Size of Higher-Order Cortical Areas.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The dynamic activity of the serine/threonine kinase Akt is crucial for the regulation of diverse cellular functions, but the precise spatiotemporal control of its activity remains a critical issue. Herein, we present a photo-activatable Akt (PA-Akt) system based on a light-inducible protein interaction module of Arabidopsis thaliana cryptochrome2 (CRY2) and CIB1. Akt fused to CRY2phr, which is a minimal light sensitive domain of CRY2 (CRY2-Akt), is reversibly activated by light illumination in several minutes within a physiological dynamic range and specifically regulates downstream molecules and inducible biological functions. We have generated a computational model of CRY2-Akt activation that allows us to use PA-Akt to control the activity quantitatively. The system provides evidence that the temporal patterns of Akt activity are crucial for generating one of the downstream functions of the Akt-FoxO pathway; the expression of a key gene involved in muscle atrophy (Atrogin-1). The use of an optical module with computational modeling represents a general framework for interrogating the temporal dynamics of biomolecules by predictive manipulation of optogenetic modules.", "classifications": [ { "id": "Kuroda", "label": "Group Kuroda", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yoshihiro", "last_name": "Katsura", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Kubota", "name": null }, { "creator_type": "author", "first_name": "Katsuyuki", "last_name": "Kunida", "name": null }, { "creator_type": "author", "first_name": "Akira", "last_name": "Kanno", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Kuroda", "name": null }, { "creator_type": "author", "first_name": "Takeaki", "last_name": "Ozawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/srep14589" }, "pmcid": { "normalized": "PMC4589684" }, "pmid": { "normalized": "26423353" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Arabidopsis Proteins", "descriptor_ui": "D029681", "major_topic": false }, { "descriptor": "Computer Simulation", "descriptor_ui": "D003198", "major_topic": false }, { "descriptor": "Cryptochromes", "descriptor_ui": "D056931", "major_topic": false }, { "descriptor": "Enzyme Induction", "descriptor_ui": "D004790", "major_topic": false }, { "descriptor": "HEK293 Cells", "descriptor_ui": "D057809", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Models, Genetic", "descriptor_ui": "D008957", "major_topic": false }, { "descriptor": "Optogenetics", "descriptor_ui": "D062308", "major_topic": false }, { "descriptor": "Phosphorylation", "descriptor_ui": "D010766", "major_topic": false }, { "descriptor": "Protein Processing, Post-Translational", "descriptor_ui": "D011499", "major_topic": false }, { "descriptor": "Proto-Oncogene Proteins c-akt", "descriptor_ui": "D051057", "major_topic": false } ], "publication": { "conference_name": null, "date": "2015 Oct 1", "date_precision": "day", "issue": "", "normalized_date": "2015-10-01", "pages": "14589", "proceedings_title": null, "publisher": "", "title": "Scientific reports", "volume": "5", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "An optogenetic system for interrogating the temporal dynamics of Akt.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Rational design to control the dynamics of molecular rotors in crystalline solids is of interest because it offers advanced materials with precisely tuned functionality. Herein, we describe the control of the rotational frequency of rotors in flexible porous coordination polymers (PCPs) using a solid-solution approach. Solid-solutions of the flexible PCPs [Zn(5-nitroisophthalate)x(5-methoxyisophthalate)1-x(deuterated 4,4'-bipyridyl)(DMF.MeOH)]n allow continuous modulation of cell volume by changing the solid-solution ratio x. Variation of the isostructures provides continuous changes in the local environment around the molecular rotors (pyridyl rings of the 4,4'-bipyridyl group), leading to the control of the rotational frequency without the need to vary the temperature.", "classifications": [ { "id": "Hijikata", "label": "Group Hijikata", "parent": "Tsuchiya", "type": "group" }, { "id": "Tsuchiya", "label": "Team Tsuchiya", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Munehiro", "last_name": "Inukai", "name": null }, { "creator_type": "author", "first_name": "Tomohiro", "last_name": "Fukushima", "name": null }, { "creator_type": "author", "first_name": "Yuh", "last_name": "Hijikata", "name": null }, { "creator_type": "author", "first_name": "Naoki", "last_name": "Ogiwara", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Horike", "name": null }, { "creator_type": "author", "first_name": "Susumu", "last_name": "Kitagawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/jacs.5b05413" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "26368067" } }, "mesh": [ { "descriptor": "HEK293 Cells", "descriptor_ui": "D057809", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Particle Size", "descriptor_ui": "D010316", "major_topic": false }, { "descriptor": "Polymers", "descriptor_ui": "D011108", "major_topic": false }, { "descriptor": "Porosity", "descriptor_ui": "D016062", "major_topic": false }, { "descriptor": "Rotation", "descriptor_ui": "D012399", "major_topic": true }, { "descriptor": "Solutions", "descriptor_ui": "D012996", "major_topic": false }, { "descriptor": "Surface Properties", "descriptor_ui": "D013499", "major_topic": false }, { "descriptor": "Temperature", "descriptor_ui": "D013696", "major_topic": false } ], "publication": { "conference_name": null, "date": "2015 Sep 30", "date_precision": "day", "issue": "38", "normalized_date": "2015-09-30", "pages": "12183-12186", "proceedings_title": null, "publisher": "", "title": "Journal of the American Chemical Society", "volume": "137", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "Control of molecular rotor rotational frequencies in porous coordination polymers using a solid-solution approach.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The p38 MAP kinase signalling pathway controls inflammatory responses and is an important target of anti-inflammatory drugs. Although pro-inflammatory cytokines such as interleukin-1beta (IL-1beta) appear to induce only transient activation of p38 (over approximately 60 min), longer cytokine exposure is necessary to induce p38-dependent effector genes. Here we study the dynamics of p38 activation in individual cells using a Forster resonance energy transfer (FRET)-based p38 activity reporter. We find that, after an initial burst of activity, p38 MAPK activity subsequently oscillates for more than 8 h under continuous IL-1beta stimulation. However, as this oscillation is asynchronous, the measured p38 activity population average is only slightly higher than basal level. Mathematical modelling, which we have experimentally verified, indicates that the asynchronous oscillation of p38 is generated through a negative feedback loop involving the dual-specificity phosphatase MKP-1/DUSP1. We find that the oscillatory p38 activity is necessary for efficient expression of pro-inflammatory genes such as IL-6, IL-8 and COX-2.", "classifications": [ { "id": "Takekawa", "label": "Group Takekawa", "parent": "Takekawa", "type": "group" }, { "id": "Takekawa", "label": "Team Takekawa", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Taichiro", "last_name": "Tomida", "name": null }, { "creator_type": "author", "first_name": "Mutsuhiro", "last_name": "Takekawa", "name": null }, { "creator_type": "author", "first_name": "Haruo", "last_name": "Saito", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/ncomms9350" }, "pmcid": { "normalized": "PMC4598561" }, "pmid": { "normalized": "26399197" } }, "mesh": [ { "descriptor": "Computer Simulation", "descriptor_ui": "D003198", "major_topic": false }, { "descriptor": "Cyclooxygenase 2", "descriptor_ui": "D051546", "major_topic": false }, { "descriptor": "Dual Specificity Phosphatase 1", "descriptor_ui": "D054638", "major_topic": false }, { "descriptor": "Feedback, Physiological", "descriptor_ui": "D025461", "major_topic": false }, { "descriptor": "Fluorescence Resonance Energy Transfer", "descriptor_ui": "D031541", "major_topic": false }, { "descriptor": "Gene Expression Regulation", "descriptor_ui": "D005786", "major_topic": false }, { "descriptor": "HeLa Cells", "descriptor_ui": "D006367", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Immunoblotting", "descriptor_ui": "D015151", "major_topic": false }, { "descriptor": "Inflammation", "descriptor_ui": "D007249", "major_topic": false }, { "descriptor": "Interleukin-1beta", "descriptor_ui": "D053583", "major_topic": false }, { "descriptor": "Interleukin-6", "descriptor_ui": "D015850", "major_topic": false }, { "descriptor": "Interleukin-8", "descriptor_ui": "D016209", "major_topic": false }, { "descriptor": "p38 Mitogen-Activated Protein Kinases", "descriptor_ui": "D048051", "major_topic": false }, { "descriptor": "RNA, Messenger", "descriptor_ui": "D012333", "major_topic": false }, { "descriptor": "Time-Lapse Imaging", "descriptor_ui": "D059008", "major_topic": false } ], "publication": { "conference_name": null, "date": "2015 Sep 24", "date_precision": "day", "issue": "", "normalized_date": "2015-09-24", "pages": "8350", "proceedings_title": null, "publisher": "", "title": "Nature communications", "volume": "6", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "Oscillation of p38 activity controls efficient pro-inflammatory gene expression.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "While N-acetyl-p-benzoquinoneimine (NAPQI), an electrophilic metabolite of acetaminophen (APAP), has been found to undergo GSH conjugation associated with its detoxification, interaction of NAPQI with nucleophilic per- and polysulfides produced by cystathionine gamma-lyase (CSE), cystathionine beta-synthase, and/or other enzymes is not known. In the present study, we found that sulfur adducts such as the NAPQIH2-SSSCys adduct and the NAPQIH2-SSG adduct are produced in biological samples of mice upon APAP exposure. Our in vitro experiments indicated that the formation of these novel APAP metabolites is, at least in part, attributable to the interaction of CysSSnSH produced by CSE and GSH persulfide with APAP-derived NAPQI.", "classifications": [ { "id": "Akaike", "label": "Group Akaike", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yumi", "last_name": "Abiko", "name": null }, { "creator_type": "author", "first_name": "Isao", "last_name": "Ishii", "name": null }, { "creator_type": "author", "first_name": "Shotaro", "last_name": "Kamata", "name": null }, { "creator_type": "author", "first_name": "Yukihiro", "last_name": "Tsuchiya", "name": null }, { "creator_type": "author", "first_name": "Yasuo", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Hideshi", "last_name": "Ihara", "name": null }, { "creator_type": "author", "first_name": "Takaaki", "last_name": "Akaike", "name": null }, { "creator_type": "author", "first_name": "Yoshito", "last_name": "Kumagai", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/acs.chemrestox.5b00245" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "26304691" } }, "mesh": [ { "descriptor": "Acetaminophen", "descriptor_ui": "D000082", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Benzoquinones", "descriptor_ui": "D016227", "major_topic": false }, { "descriptor": "Chromatography, Liquid", "descriptor_ui": "D002853", "major_topic": false }, { "descriptor": "Imines", "descriptor_ui": "D007097", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Sulfides", "descriptor_ui": "D013440", "major_topic": false }, { "descriptor": "Sulfur", "descriptor_ui": "D013455", "major_topic": false }, { "descriptor": "Tandem Mass Spectrometry", "descriptor_ui": "D053719", "major_topic": false } ], "publication": { "conference_name": null, "date": "2015 Sep 21", "date_precision": "day", "issue": "9", "normalized_date": "2015-09-21", "pages": "1796-1802", "proceedings_title": null, "publisher": "", "title": "Chemical research in toxicology", "volume": "28", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "Formation of sulfur adducts of N-acetyl-p-benzoquinoneimine, an electrophilic metabolite of acetaminophen in vivo: participation of reactive persulfides.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The external electric field effects on the steady-state electronic spectra and excited-state dynamics were investigated for 4'-N,N-(dimethylamino)-3-hydroxyflavone (DMHF) in a poly(methyl methacrylate) (PMMA) film. In the steady-state spectrum, dual emission was observed from the excited states of the normal (N*) and tautomer (T*) forms. Application of an external electric field of 1.0 MV.cm(-1) enhanced the N* emission and reduced the T* emission, indicating that the external electric field suppressed the excited-state intramolecular proton transfer (ESIPT). The fluorescence decay profiles were measured for the N* and T* forms. The change in the emission intensity ratio N*/T* induced by the external electric field is dominated by ESIPT from the Franck-Condon excited state of the N* form and vibrational cooling in potential wells of the N* and T* forms occurring within tens of picoseconds. Three manifolds of fluorescent states were identified for both the N* and T* forms. The excited-state dynamics of DMHF in PMMA films has been found to be very different from that in solution due to intermolecular interactions in a rigid environment.", "classifications": [ { "id": "Nakabayashi", "label": "Group Nakabayashi", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Kazuki", "last_name": "Furukawa", "name": null }, { "creator_type": "author", "first_name": "Kazuyuki", "last_name": "Hino", "name": null }, { "creator_type": "author", "first_name": "Norifumi", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Kamlesh", "last_name": "Awasthi", "name": null }, { "creator_type": "author", "first_name": "Takakazu", "last_name": "Nakabayashi", "name": null }, { "creator_type": "author", "first_name": "Nobuhiro", "last_name": "Ohta", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Sekiya", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/acs.jpca.5b03672" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "26301571" } }, "mesh": [ { "descriptor": "Electricity", "descriptor_ui": "D004560", "major_topic": true }, { "descriptor": "Flavonoids", "descriptor_ui": "D005419", "major_topic": false }, { "descriptor": "Models, Chemical", "descriptor_ui": "D008956", "major_topic": false }, { "descriptor": "Molecular Dynamics Simulation", "descriptor_ui": "D056004", "major_topic": false }, { "descriptor": "Molecular Structure", "descriptor_ui": "D015394", "major_topic": false }, { "descriptor": "Polymethyl Methacrylate", "descriptor_ui": "D019904", "major_topic": false }, { "descriptor": "Protons", "descriptor_ui": "D011522", "major_topic": true }, { "descriptor": "Quantum Theory", "descriptor_ui": "D011789", "major_topic": true }, { "descriptor": "Spectrometry, Fluorescence", "descriptor_ui": "D013050", "major_topic": false } ], "publication": { "conference_name": null, "date": "2015 Sep 17", "date_precision": "day", "issue": "37", "normalized_date": "2015-09-17", "pages": "9599-9608", "proceedings_title": null, "publisher": "", "title": "The journal of physical chemistry. A", "volume": "119", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "External Electric Field Effects on Excited-State Intramolecular Proton Transfer in 4'-N,N-Dimethylamino-3-hydroxyflavone in Poly(methyl methacrylate) Films.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Axon growth is a crucial process in regeneration of damaged nerves. On the other hand, elongation of nerve fibers in the epidermis has been observed in skin of atopic dermatitis patients. Thus, regulation of nerve fiber extension might be an effective strategy to accelerate nerve regeneration and/or to reduce itching in pruritus dermatosis. We previously demonstrated that neurons and epidermal keratinocytes similarly contain multiple receptors that are activated by various environmental factors, and in particular, keratinocytes are influenced by shear stress. Thus, in the present study, we evaluated the effects of micro-flow of the medium on axon growth in the presence or absence of nerve growth factor (NGF), using cultured dorsal-root-ganglion (DRG) cells. The apparatus, AXIS, consists of two chambers connected by a set of microgrooves, through which signaling molecules and axons, but not living cells, can pass. When DRG cells were present in chamber 1, NGF was present in chamber 2, and micro-flow was directed from chamber 1 to chamber 2, axon growth was significantly increased compared with other conditions. Acceleration of axon growth in the direction of the micro-flow was also observed in the absence of NGF. These results suggest that local micro-flow might significantly influence axon growth.", "classifications": [ { "id": "Nagayama", "label": "Group Nagayama", "parent": "Fujiwara", "type": "group" }, { "id": "Fujiwara", "label": "Team Fujiwara", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Junichi", "last_name": "Kumamoto", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Kitahata", "name": null }, { "creator_type": "author", "first_name": "Makiko", "last_name": "Goto", "name": null }, { "creator_type": "author", "first_name": "Masaharu", "last_name": "Nagayama", "name": null }, { "creator_type": "author", "first_name": "Mitsuhiro", "last_name": "Denda", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.bbrc.2015.07.104" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "26212442" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Axons", "descriptor_ui": "D001369", "major_topic": false }, { "descriptor": "Biomechanical Phenomena", "descriptor_ui": "D001696", "major_topic": false }, { "descriptor": "Diffusion", "descriptor_ui": "D004058", "major_topic": false }, { "descriptor": "Diffusion Chambers, Culture", "descriptor_ui": "D015194", "major_topic": false }, { "descriptor": "Ganglia, Spinal", "descriptor_ui": "D005727", "major_topic": false }, { "descriptor": "Nerve Growth Factor", "descriptor_ui": "D020932", "major_topic": false }, { "descriptor": "Primary Cell Culture", "descriptor_ui": "D061251", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Rheology", "descriptor_ui": "D012212", "major_topic": false }, { "descriptor": "Sensory Receptor Cells", "descriptor_ui": "D011984", "major_topic": false } ], "publication": { "conference_name": null, "date": "2015 Sep 11", "date_precision": "day", "issue": "1", "normalized_date": "2015-09-11", "pages": "26-29", "proceedings_title": null, "publisher": "", "title": "Biochemical and biophysical research communications", "volume": "465", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "Effects of medium flow on axon growth with or without nerve growth factor.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Background: The highly related small GTPases RalA and RalB exhibit distinct functions in cancer cell processes.Results: Posttranslational modifications signaled by the C-terminal CAAX motif contribute to Ral isoform differences in subcellular localization, activation, and protein stability.Conclusion: Modifications catalyzed by RCE1, ICMT, and protein palmitoyl acyltransferase cause Ral isoform-specific functional consequences.Significance: Inhibitors of CAAX motif modifications will have complex consequences on Ral GTPase regulation.", "classifications": [ { "id": "Nishida", "label": "Group Nishida", "parent": "Nishida", "type": "group" }, { "id": "Nishimura", "label": "Group Nishimura", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Leanna R.", "last_name": "Gentry", "name": null }, { "creator_type": "author", "first_name": "Akiyuki", "last_name": "Nishimura", "name": null }, { "creator_type": "author", "first_name": "Adrienne D.", "last_name": "Cox", "name": null }, { "creator_type": "author", "first_name": "Timothy D.", "last_name": "Martin", "name": null }, { "creator_type": "author", "first_name": "Denis", "last_name": "Tsygankov", "name": null }, { "creator_type": "author", "first_name": "Motohiro", "last_name": "Nishida", "name": null }, { "creator_type": "author", "first_name": "Timothy C.", "last_name": "Elston", "name": null }, { "creator_type": "author", "first_name": "Channing J.", "last_name": "Der", "name": null } ], "identifiers": { "doi": { "normalized": "10.1074/jbc.m115.656710" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "26216878" } }, "mesh": [ { "descriptor": "Amino Acid Motifs", "descriptor_ui": "D020816", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Membrane", "descriptor_ui": "D002462", "major_topic": false }, { "descriptor": "Endosomes", "descriptor_ui": "D011992", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Protein Processing, Post-Translational", "descriptor_ui": "D011499", "major_topic": false }, { "descriptor": "Protein Transport", "descriptor_ui": "D021381", "major_topic": false }, { "descriptor": "ral GTP-Binding Proteins", "descriptor_ui": "D020725", "major_topic": false } ], "publication": { "conference_name": null, "date": "2015 Sep 11", "date_precision": "day", "issue": "37", "normalized_date": "2015-09-11", "pages": "22851-22861", "proceedings_title": null, "publisher": "", "title": "The Journal of Biological Chemistry", "volume": "290", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "Divergent Roles of CAAX Motif-signaled Posttranslational Modifications in the Regulation and Subcellular Localization of Ral GTPases*.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Intravenous administration of high-dose vitamin C has recently attracted attention as a cancer therapy. High-dose vitamin C induces pro-oxidant effects and selectively kills cancer cells. However, the anticancer mechanisms of vitamin C are not fully understood. Here, we analyzed metabolic changes induced by vitamin C in MCF7 human breast adenocarcinoma and HT29 human colon cancer cells using capillary electrophoresis time-of-flight mass spectrometry (CE-TOFMS). The metabolomic profiles of both cell lines were dramatically altered after exposure to cytotoxic concentrations of vitamin C. Levels of upstream metabolites in the glycolysis pathway and tricarboxylic acid (TCA) cycle were increased in both cell lines following treatment with vitamin C, while adenosine triphosphate (ATP) levels and adenylate energy charges were decreased concentration-dependently. Treatment with N-acetyl cysteine (NAC) and reduced glutathione (GSH) significantly inhibited vitamin C-induced cytotoxicity in MCF7 cells. NAC also suppressed vitamin C-dependent metabolic changes, and NAD treatment prevented vitamin C-induced cell death. Collectively, our data suggests that vitamin C inhibited energy metabolism through NAD depletion, thereby inducing cancer cell death.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Megumi", "last_name": "Uetaki", "name": null }, { "creator_type": "author", "first_name": "Sho", "last_name": "Tabata", "name": null }, { "creator_type": "author", "first_name": "Fumie", "last_name": "Nakasuka", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Masaru", "last_name": "Tomita", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/srep13896" }, "pmcid": { "normalized": "PMC4563566" }, "pmid": { "normalized": "26350063" } }, "mesh": [ { "descriptor": "Ascorbic Acid", "descriptor_ui": "D001205", "major_topic": false }, { "descriptor": "Cell Survival", "descriptor_ui": "D002470", "major_topic": false }, { "descriptor": "Energy Metabolism", "descriptor_ui": "D004734", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Hydrogen Peroxide", "descriptor_ui": "D006861", "major_topic": false }, { "descriptor": "MCF-7 Cells", "descriptor_ui": "D061986", "major_topic": false }, { "descriptor": "Metabolome", "descriptor_ui": "D055442", "major_topic": true }, { "descriptor": "Metabolomics", "descriptor_ui": "D055432", "major_topic": true }, { "descriptor": "NAD", "descriptor_ui": "D009243", "major_topic": false }, { "descriptor": "Neoplasms", "descriptor_ui": "D009369", "major_topic": false }, { "descriptor": "Oxidative Stress", "descriptor_ui": "D018384", "major_topic": true } ], "publication": { "conference_name": null, "date": "2015 Sep 9", "date_precision": "day", "issue": "", "normalized_date": "2015-09-09", "pages": "13896", "proceedings_title": null, "publisher": "", "title": "Scientific reports", "volume": "5", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "Metabolomic alterations in human cancer cells by vitamin C-induced oxidative stress.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The precise assemblage of several types of cardiac precursors controls heart organogenesis. The cardiac precursors show dynamic movement during early development and then form the complicated heart structure. However, cardiomyocyte movements inside the newly organized mammalian heart remain unclear. We previously established the method of ex vivo time-lapse imaging of the murine heart to study cardiomyocyte behavior by using the Fucci (fluorescent ubiquitination-based cell cycle indicator) system, which can effectively label individual G1, S/G2/M, and G1/S-transition phase nuclei in living cardiomyocytes as red, green, and yellow, respectively. Global analysis of gene expression in Fucci green positive ventricular cardiomyocytes confirmed that cell cycle regulatory genes expressed in G1/S, S, G2/M, and M phase transitions were upregulated. Interestingly, pathway analysis revealed that many genes related to the cell cycle were significantly upregulated in the Fucci green positive ventricular cardiomyocytes, while only a small number of genes related to cell motility were upregulated. Time-lapse imaging showed that murine proliferating cardiomyocytes did not exhibit dynamic movement inside the heart, but stayed on site after entering the cell cycle.", "classifications": [ { "id": "Sawano", "label": "Group Sawano", "parent": "Shintaku", "type": "group" }, { "id": "Shintaku", "label": "Team Shintaku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Hisayuki", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Shinsuke", "last_name": "Yuasa", "name": null }, { "creator_type": "author", "first_name": "Hidenori", "last_name": "Tabata", "name": null }, { "creator_type": "author", "first_name": "Shugo", "last_name": "Tohyama", "name": null }, { "creator_type": "author", "first_name": "Tomohisa", "last_name": "Seki", "name": null }, { "creator_type": "author", "first_name": "Toru", "last_name": "Egashira", "name": null }, { "creator_type": "author", "first_name": "Nozomi", "last_name": "Hayashiji", "name": null }, { "creator_type": "author", "first_name": "Fumiyuki", "last_name": "Hattori", "name": null }, { "creator_type": "author", "first_name": "Dai", "last_name": "Kusumoto", "name": null }, { "creator_type": "author", "first_name": "Akira", "last_name": "Kunitomi", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Takei", "name": null }, { "creator_type": "author", "first_name": "Shin", "last_name": "Kashimura", "name": null }, { "creator_type": "author", "first_name": "Gakuto", "last_name": "Yozu", "name": null }, { "creator_type": "author", "first_name": "Masaya", "last_name": "Shimojima", "name": null }, { "creator_type": "author", "first_name": "Chikaaki", "last_name": "Motoda", "name": null }, { "creator_type": "author", "first_name": "Naoto", "last_name": "Muraoka", "name": null }, { "creator_type": "author", "first_name": "Kazunori", "last_name": "Nakajima", "name": null }, { "creator_type": "author", "first_name": "Asako", "last_name": "Sakaue-Sawano", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Miyawaki", "name": null }, { "creator_type": "author", "first_name": "Keiichi", "last_name": "Fukuda", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.bbrc.2015.07.036" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "26168730" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Cycle Checkpoints", "descriptor_ui": "D059447", "major_topic": false }, { "descriptor": "Cell Movement", "descriptor_ui": "D002465", "major_topic": false }, { "descriptor": "Cell Proliferation", "descriptor_ui": "D049109", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Fetal Heart", "descriptor_ui": "D005318", "major_topic": false }, { "descriptor": "Gene Expression Regulation, Developmental", "descriptor_ui": "D018507", "major_topic": false }, { "descriptor": "Genes, Reporter", "descriptor_ui": "D017930", "major_topic": false }, { "descriptor": "Heart", "descriptor_ui": "D006321", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Transgenic", "descriptor_ui": "D008822", "major_topic": false }, { "descriptor": "Myocardium", "descriptor_ui": "D009206", "major_topic": false }, { "descriptor": "Myocytes, Cardiac", "descriptor_ui": "D032383", "major_topic": false }, { "descriptor": "Oligonucleotide Array Sequence Analysis", "descriptor_ui": "D020411", "major_topic": false }, { "descriptor": "Pregnancy", "descriptor_ui": "D011247", "major_topic": false } ], "publication": { "conference_name": null, "date": "2015 Sep 4", "date_precision": "day", "issue": "4", "normalized_date": "2015-09-04", "pages": "1000-1007", "proceedings_title": null, "publisher": "", "title": "Biochemical and biophysical research communications", "volume": "464", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "Analysis of cardiomyocyte movement in the developing murine heart.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The anti-tumor activity of gemcitabine (GEM) has been clinically proven in several solid tumors, including pancreatic cancer, biliary tract cancer, urinary bladder cancer, and non-small cell lung cancer. However, problems remain with issues such as acquisition of chemoresistance against GEM. GEM is activated after phosphorylation by deoxycytidine kinase (DCK) inside of the cell; thus, DCK inactivation is one of the important mechanisms for acquisition of GEM resistance. We previously investigated the DCK gene in multiple GEM resistant cancer cell lines and identified frequent inactivating mutations. In this study, we identified two crucial genetic alteration in DCK. (1) A total deletion of DCK in RTGBC1-TKB, an acquired GEM resistant cell line derived from a gall bladder cancer cell line TGBC1-TKB. (2) An E197K missense alteration of DCK in MKN28, a gastric cancer cell line; its acquired GEM resistant cancer cell line, RMKN28, showed a loss of the normal E197 allele. We introduced either normal DCK or altered DCK_E197K into RMKN28 and proved that only the introduction of normal DCK restored GEM sensitivity. Furthermore, we analyzed 104 healthy volunteers and found that none of them carried the same base substitution observed in MKN28. These results strongly suggest that (1) the E197K alteration in DCK causes inactivation of DCK, and that (2) loss of the normal E197 allele is the crucial mechanism in acquisition of GEM resistance in RMKN28.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Tomohiro", "last_name": "Nakano", "name": null }, { "creator_type": "author", "first_name": "Yuriko", "last_name": "Saiki", "name": null }, { "creator_type": "author", "first_name": "Chiharu", "last_name": "Kudo", "name": null }, { "creator_type": "author", "first_name": "Akiyoshi", "last_name": "Hirayama", "name": null }, { "creator_type": "author", "first_name": "Yasuhiko", "last_name": "Mizuguchi", "name": null }, { "creator_type": "author", "first_name": "Sho", "last_name": "Fujiwara", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Sunamura", "name": null }, { "creator_type": "author", "first_name": "Nobutoshi", "last_name": "Matsumura", "name": null }, { "creator_type": "author", "first_name": "Fuyuhiko", "last_name": "Motoi", "name": null }, { "creator_type": "author", "first_name": "Michiaki", "last_name": "Unno", "name": null }, { "creator_type": "author", "first_name": "Akira", "last_name": "Horii", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.bbrc.2015.07.080" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "26196746" } }, "mesh": [ { "descriptor": "Amino Acid Substitution", "descriptor_ui": "D019943", "major_topic": false }, { "descriptor": "Antineoplastic Agents", "descriptor_ui": "D000970", "major_topic": false }, { "descriptor": "Base Sequence", "descriptor_ui": "D001483", "major_topic": false }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Deoxycytidine", "descriptor_ui": "D003841", "major_topic": false }, { "descriptor": "Deoxycytidine Kinase", "descriptor_ui": "D003842", "major_topic": false }, { "descriptor": "DNA Damage", "descriptor_ui": "D004249", "major_topic": false }, { "descriptor": "DNA Mutational Analysis", "descriptor_ui": "D004252", "major_topic": false }, { "descriptor": "DNA, Neoplasm", "descriptor_ui": "D004273", "major_topic": false }, { "descriptor": "Drug Resistance, Neoplasm", "descriptor_ui": "D019008", "major_topic": false }, { "descriptor": "Exons", "descriptor_ui": "D005091", "major_topic": false }, { "descriptor": "Gallbladder Neoplasms", "descriptor_ui": "D005706", "major_topic": false }, { "descriptor": "Gemcitabine", "descriptor_ui": "D000093542", "major_topic": false }, { "descriptor": "Gene Deletion", "descriptor_ui": "D017353", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mutation, Missense", "descriptor_ui": "D020125", "major_topic": true } ], "publication": { "conference_name": null, "date": "2015 Sep 4", "date_precision": "day", "issue": "4", "normalized_date": "2015-09-04", "pages": "1084-1089", "proceedings_title": null, "publisher": "", "title": "Biochemical and biophysical research communications", "volume": "464", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "Acquisition of chemoresistance to gemcitabine is induced by a loss-of-function missense mutation of DCK.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Elucidating the signaling mechanism of strigolactones has been the key to controlling the devastating problem caused by the parasitic plant Striga hermonthica. To overcome the genetic intractability that has previously interfered with identification of the strigolactone receptor, we developed a fluorescence turn-on probe, Yoshimulactone Green (YLG), which activates strigolactone signaling and illuminates signal perception by the strigolactone receptors. Here we describe how strigolactones bind to and act via ShHTLs, the diverged family of alpha/beta hydrolase-fold proteins in Striga. Live imaging using YLGs revealed that a dynamic wavelike propagation of strigolactone perception wakes up Striga seeds. We conclude that ShHTLs function as the strigolactone receptors mediating seed germination in Striga. Our findings enable access to strigolactone receptors and observation of the regulatory dynamics for strigolactone signal transduction in Striga.", "classifications": [ { "id": "Sato", "label": "Group Sato", "parent": "Tsuchiya", "type": "group" }, { "id": "Tsuchiya", "label": "Group Tsuchiya", "parent": "Tsuchiya", "type": "group" }, { "id": "Tsuchiya", "label": "Team Tsuchiya", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yuichiro", "last_name": "Tsuchiya", "name": null }, { "creator_type": "author", "first_name": "Masahiko", "last_name": "Yoshimura", "name": null }, { "creator_type": "author", "first_name": "Yoshikatsu", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Keiko", "last_name": "Kuwata", "name": null }, { "creator_type": "author", "first_name": "Shigeo", "last_name": "Toh", "name": null }, { "creator_type": "author", "first_name": "Duncan", "last_name": "Holbrook-Smith", "name": null }, { "creator_type": "author", "first_name": "Hua", "last_name": "Zhang", "name": null }, { "creator_type": "author", "first_name": "Peter", "last_name": "McCourt", "name": null }, { "creator_type": "author", "first_name": "Kenichiro", "last_name": "Itami", "name": null }, { "creator_type": "author", "first_name": "Toshinori", "last_name": "Kinoshita", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Hagihara", "name": null } ], "identifiers": { "doi": { "normalized": "10.1126/science.aab3831" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "26293962" } }, "mesh": [ { "descriptor": "Fluoresceins", "descriptor_ui": "D005452", "major_topic": false }, { "descriptor": "Fluorescence", "descriptor_ui": "D005453", "major_topic": false }, { "descriptor": "Fluorescent Dyes", "descriptor_ui": "D005456", "major_topic": false }, { "descriptor": "Germination", "descriptor_ui": "D018525", "major_topic": true }, { "descriptor": "Hydrolases", "descriptor_ui": "D006867", "major_topic": false }, { "descriptor": "Hydrolysis", "descriptor_ui": "D006868", "major_topic": false }, { "descriptor": "Lactones", "descriptor_ui": "D007783", "major_topic": false }, { "descriptor": "Molecular Imaging", "descriptor_ui": "D057054", "major_topic": false }, { "descriptor": "Molecular Sequence Data", "descriptor_ui": "D008969", "major_topic": false }, { "descriptor": "Plant Growth Regulators", "descriptor_ui": "D010937", "major_topic": false }, { "descriptor": "Plant Proteins", "descriptor_ui": "D010940", "major_topic": false }, { "descriptor": "Receptors, Cell Surface", "descriptor_ui": "D011956", "major_topic": false }, { "descriptor": "Seeds", "descriptor_ui": "D012639", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Striga", "descriptor_ui": "D034362", "major_topic": false } ], "publication": { "conference_name": null, "date": "2015 Aug 21", "date_precision": "day", "issue": "6250", "normalized_date": "2015-08-21", "pages": "864-868", "proceedings_title": null, "publisher": "", "title": "Science (New York, N.Y.)", "volume": "349", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "PARASITIC PLANTS. Probing strigolactone receptors in Striga hermonthica with fluorescence.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Mechanisms underlying human germ cell development are unclear, partly due to difficulties in studying human embryos and lack of suitable experimental systems. Here, we show that human induced pluripotent stem cells (hiPSCs) differentiate into incipient mesoderm-like cells (iMeLCs), which robustly generate human primordial germ cell-like cells (hPGCLCs) that can be purified using the surface markers EpCAM and INTEGRINalpha6. The transcriptomes of hPGCLCs and primordial germ cells (PGCs) isolated from non-human primates are similar, and although specification of hPGCLCs and mouse PGCs rely on similar signaling pathways, hPGCLC specification transcriptionally activates germline fate without transiently inducing eminent somatic programs. This includes genes important for naive pluripotency and repression of key epigenetic modifiers, concomitant with epigenetic reprogramming. Accordingly, BLIMP1, which represses somatic programs in mice, activates and stabilizes a germline transcriptional circuit and represses a default neuronal differentiation program. Together, these findings provide a foundation for understanding and reconstituting human germ cell development in vitro.", "classifications": [ { "id": "Yamamoto", "label": "Group Yamamoto", "parent": "Toyoshima", "type": "group" }, { "id": "Toyoshima", "label": "Team Toyoshima", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Kotaro", "last_name": "Sasaki", "name": null }, { "creator_type": "author", "first_name": "Shihori", "last_name": "Yokobayashi", "name": null }, { "creator_type": "author", "first_name": "Tomonori", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Ikuhiro", "last_name": "Okamoto", "name": null }, { "creator_type": "author", "first_name": "Yukihiro", "last_name": "Yabuta", "name": null }, { "creator_type": "author", "first_name": "Kazuki", "last_name": "Kurimoto", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Ohta", "name": null }, { "creator_type": "author", "first_name": "Yoshinobu", "last_name": "Moritoki", "name": null }, { "creator_type": "author", "first_name": "Chizuru", "last_name": "Iwatani", "name": null }, { "creator_type": "author", "first_name": "Hideaki", "last_name": "Tsuchiya", "name": null }, { "creator_type": "author", "first_name": "Shinichiro", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Kiyotoshi", "last_name": "Sekiguchi", "name": null }, { "creator_type": "author", "first_name": "Tetsushi", "last_name": "Sakuma", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Takahide", "last_name": "Mori", "name": null }, { "creator_type": "author", "first_name": "Knut", "last_name": "Woltjen", "name": null }, { "creator_type": "author", "first_name": "Masato", "last_name": "Nakagawa", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Kazutoshi", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Yamanaka", "name": null }, { "creator_type": "author", "first_name": "Mitinori", "last_name": "Saitou", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.stem.2015.06.014" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "26189426" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Base Sequence", "descriptor_ui": "D001483", "major_topic": false }, { "descriptor": "Biomarkers", "descriptor_ui": "D015415", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Cell Lineage", "descriptor_ui": "D019070", "major_topic": true }, { "descriptor": "Epigenesis, Genetic", "descriptor_ui": "D044127", "major_topic": false }, { "descriptor": "Genes, Reporter", "descriptor_ui": "D017930", "major_topic": false }, { "descriptor": "Germ Cells", "descriptor_ui": "D005854", "major_topic": false }, { "descriptor": "Gonads", "descriptor_ui": "D006066", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Induced Pluripotent Stem Cells", "descriptor_ui": "D057026", "major_topic": false }, { "descriptor": "Macaca fascicularis", "descriptor_ui": "D008252", "major_topic": false }, { "descriptor": "Mesoderm", "descriptor_ui": "D008648", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Molecular Sequence Data", "descriptor_ui": "D008969", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Positive Regulatory Domain I-Binding Factor 1", "descriptor_ui": "D000074462", "major_topic": false }, { "descriptor": "Repressor Proteins", "descriptor_ui": "D012097", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Transcription, Genetic", "descriptor_ui": "D014158", "major_topic": false } ], "publication": { "conference_name": null, "date": "2015 Aug 6", "date_precision": "day", "issue": "2", "normalized_date": "2015-08-06", "pages": "178-194", "proceedings_title": null, "publisher": "", "title": "Cell stem cell", "volume": "17", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "Robust In Vitro Induction of Human Germ Cell Fate from Pluripotent Stem Cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "We have sequenced the genomes of 110 small cell lung cancers (SCLC), one of the deadliest human cancers. In nearly all the tumours analysed we found bi-allelic inactivation of TP53 and RB1, sometimes by complex genomic rearrangements. Two tumours with wild-type RB1 had evidence of chromothripsis leading to overexpression of cyclin D1 (encoded by the CCND1 gene), revealing an alternative mechanism of Rb1 deregulation. Thus, loss of the tumour suppressors TP53 and RB1 is obligatory in SCLC. We discovered somatic genomic rearrangements of TP73 that create an oncogenic version of this gene, TP73Deltaex2/3. In rare cases, SCLC tumours exhibited kinase gene mutations, providing a possible therapeutic opportunity for individual patients. Finally, we observed inactivating mutations in NOTCH family genes in 25% of human SCLC. Accordingly, activation of Notch signalling in a pre-clinical SCLC mouse model strikingly reduced the number of tumours and extended the survival of the mutant mice. Furthermore, neuroendocrine gene expression was abrogated by Notch activity in SCLC cells. This first comprehensive study of somatic genome alterations in SCLC uncovers several key biological processes and identifies candidate therapeutic targets in this highly lethal form of cancer.", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Julie", "last_name": "George", "name": null }, { "creator_type": "author", "first_name": "Jing Shan", "last_name": "Lim", "name": null }, { "creator_type": "author", "first_name": "Se Jin", "last_name": "Jang", "name": null }, { "creator_type": "author", "first_name": "Yupeng", "last_name": "Cun", "name": null }, { "creator_type": "author", "first_name": "Luka", "last_name": "Ozretic", "name": null }, { "creator_type": "author", "first_name": "Gu", "last_name": "Kong", "name": null }, { "creator_type": "author", "first_name": "Frauke", "last_name": "Leenders", "name": null }, { "creator_type": "author", "first_name": "Xin", "last_name": "Lu", "name": null }, { "creator_type": "author", "first_name": "Lynnette", "last_name": "Fernandez-Cuesta", "name": null }, { "creator_type": "author", "first_name": "Graziella", "last_name": "Bosco", "name": null }, { "creator_type": "author", "first_name": "Christian", "last_name": "Muller", "name": null }, { "creator_type": "author", "first_name": "Ilona", "last_name": "Dahmen", "name": null }, { "creator_type": "author", "first_name": "Nadine S.", "last_name": "Jahchan", "name": null }, { "creator_type": "author", "first_name": "Kwon-Sik", "last_name": "Park", "name": null }, { "creator_type": "author", "first_name": "Dian", "last_name": "Yang", "name": null }, { "creator_type": "author", "first_name": "Anthony N.", "last_name": "Karnezis", "name": null }, { "creator_type": "author", "first_name": "Dedeepya", "last_name": "Vaka", "name": null }, { "creator_type": "author", "first_name": "Angela", "last_name": "Torres", "name": null }, { "creator_type": "author", "first_name": "Maia Segura", "last_name": "Wang", "name": null }, { "creator_type": "author", "first_name": "Jan O.", "last_name": "Korbel", "name": null }, { "creator_type": "author", "first_name": "Roopika", "last_name": "Menon", "name": null }, { "creator_type": "author", "first_name": "Sung-Min", "last_name": "Chun", "name": null }, { "creator_type": "author", "first_name": "Deokhoon", "last_name": "Kim", "name": null }, { "creator_type": "author", "first_name": "Matt", "last_name": "Wilkerson", "name": null }, { "creator_type": "author", "first_name": "Neil", "last_name": "Hayes", "name": null }, { "creator_type": "author", "first_name": "David", "last_name": "Engelmann", "name": null }, { "creator_type": "author", "first_name": "Brigitte", "last_name": "Putzer", "name": null }, { "creator_type": "author", "first_name": "Marc", "last_name": "Bos", "name": null }, { "creator_type": "author", "first_name": "Sebastian", "last_name": "Michels", "name": null }, { "creator_type": "author", "first_name": "Ignacija", "last_name": "Vlasic", "name": null }, { "creator_type": "author", "first_name": "Danila", "last_name": "Seidel", "name": null }, { "creator_type": "author", "first_name": "Berit", "last_name": "Pinther", "name": null }, { "creator_type": "author", "first_name": "Philipp", "last_name": "Schaub", "name": null }, { "creator_type": "author", "first_name": "Christian", "last_name": "Becker", "name": null }, { "creator_type": "author", "first_name": "Janine", "last_name": "Altmuller", "name": null }, { "creator_type": "author", "first_name": "Jun", "last_name": "Yokota", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Kohno", "name": null }, { "creator_type": "author", "first_name": "Reika", "last_name": "Iwakawa", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Tsuta", "name": null }, { "creator_type": "author", "first_name": "Masayuki", "last_name": "Noguchi", "name": null }, { "creator_type": "author", "first_name": "Thomas", "last_name": "Muley", "name": null }, { "creator_type": "author", "first_name": "Hans", "last_name": "Hoffmann", "name": null }, { "creator_type": "author", "first_name": "Philipp A.", "last_name": "Schnabel", "name": null }, { "creator_type": "author", "first_name": "Iver", "last_name": "Petersen", "name": null }, { "creator_type": "author", "first_name": "Yuan", "last_name": "Chen", "name": null }, { "creator_type": "author", "first_name": "Alex", "last_name": "Soltermann", "name": null }, { "creator_type": "author", "first_name": "Verena", "last_name": "Tischler", "name": null }, { "creator_type": "author", "first_name": "Chang-min", "last_name": "Choi", "name": null }, { "creator_type": "author", "first_name": "Yong-Hee", "last_name": "Kim", "name": null }, { "creator_type": "author", "first_name": "Pierre P.", "last_name": "Massion", "name": null }, { "creator_type": "author", "first_name": "Yong", "last_name": "Zou", "name": null }, { "creator_type": "author", "first_name": "Dragana", "last_name": "Jovanovic", "name": null }, { "creator_type": "author", "first_name": "Milica", "last_name": "Kontic", "name": null }, { "creator_type": "author", "first_name": "Gavin M.", "last_name": "Wright", "name": null }, { "creator_type": "author", "first_name": "Prudence A.", "last_name": "Russell", "name": null }, { "creator_type": "author", "first_name": "Benjamin", "last_name": "Solomon", "name": null }, { "creator_type": "author", "first_name": "Ina", "last_name": "Koch", "name": null }, { "creator_type": "author", "first_name": "Michael", "last_name": "Lindner", "name": null }, { "creator_type": "author", "first_name": "Lucia A.", "last_name": "Muscarella", "name": null }, { "creator_type": "author", "first_name": "Annamaria", "last_name": "la Torre", "name": null }, { "creator_type": "author", "first_name": "John K.", "last_name": "Field", "name": null }, { "creator_type": "author", "first_name": "Marko", "last_name": "Jakopovic", "name": null }, { "creator_type": "author", "first_name": "Jelena", "last_name": "Knezevic", "name": null }, { "creator_type": "author", "first_name": "Esmeralda", "last_name": "Castanos-Velez", "name": null }, { "creator_type": "author", "first_name": "Luca", "last_name": "Roz", "name": null }, { "creator_type": "author", "first_name": "Ugo", "last_name": "Pastorino", "name": null }, { "creator_type": "author", "first_name": "Odd-Terje", "last_name": "Brustugun", "name": null }, { "creator_type": "author", "first_name": "Marius", "last_name": "Lund-Iversen", "name": null }, { "creator_type": "author", "first_name": "Erik", "last_name": "Thunnissen", "name": null }, { "creator_type": "author", "first_name": "Jens", "last_name": "Kohler", "name": null }, { "creator_type": "author", "first_name": "Martin", "last_name": "Schuler", "name": null }, { "creator_type": "author", "first_name": "Johan", "last_name": "Botling", "name": null }, { "creator_type": "author", "first_name": "Martin", "last_name": "Sandelin", "name": null }, { "creator_type": "author", "first_name": "Montserrat", "last_name": "Sanchez-Cespedes", "name": null }, { "creator_type": "author", "first_name": "Helga B.", "last_name": "Salvesen", "name": null }, { "creator_type": "author", "first_name": "Viktor", "last_name": "Achter", "name": null }, { "creator_type": "author", "first_name": "Ulrich", "last_name": "Lang", "name": null }, { "creator_type": "author", "first_name": "Magdalena", "last_name": "Bogus", "name": null }, { "creator_type": "author", "first_name": "Peter M.", "last_name": "Schneider", "name": null }, { "creator_type": "author", "first_name": "Thomas", "last_name": "Zander", "name": null }, { "creator_type": "author", "first_name": "Sascha", "last_name": "Ansen", "name": null }, { "creator_type": "author", "first_name": "Michael", "last_name": "Hallek", "name": null }, { "creator_type": "author", "first_name": "Jurgen", "last_name": "Wolf", "name": null }, { "creator_type": "author", "first_name": "Martin", "last_name": "Vingron", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null }, { "creator_type": "author", "first_name": "William D.", "last_name": "Travis", "name": null }, { "creator_type": "author", "first_name": "Peter", "last_name": "Nurnberg", "name": null }, { "creator_type": "author", "first_name": "Christian", "last_name": "Reinhardt", "name": null }, { "creator_type": "author", "first_name": "Sven", "last_name": "Perner", "name": null }, { "creator_type": "author", "first_name": "Lukas", "last_name": "Heukamp", "name": null }, { "creator_type": "author", "first_name": "Reinhard", "last_name": "Buttner", "name": null }, { "creator_type": "author", "first_name": "Stefan A.", "last_name": "Haas", "name": null }, { "creator_type": "author", "first_name": "Elisabeth", "last_name": "Brambilla", "name": null }, { "creator_type": "author", "first_name": "Martin", "last_name": "Peifer", "name": null }, { "creator_type": "author", "first_name": "Julien", "last_name": "Sage", "name": null }, { "creator_type": "author", "first_name": "Roman K.", "last_name": "Thomas", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/nature14664" }, "pmcid": { "normalized": "PMC4861069" }, "pmid": { "normalized": "26168399" } }, "mesh": [ { "descriptor": "Alleles", "descriptor_ui": "D000483", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Chromosome Breakpoints", "descriptor_ui": "D056905", "major_topic": false }, { "descriptor": "Cyclin D1", "descriptor_ui": "D019938", "major_topic": false }, { "descriptor": "Disease Models, Animal", "descriptor_ui": "D004195", "major_topic": false }, { "descriptor": "DNA-Binding Proteins", "descriptor_ui": "D004268", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Gene Expression Profiling", "descriptor_ui": "D020869", "major_topic": false }, { "descriptor": "Genome, Human", "descriptor_ui": "D015894", "major_topic": false }, { "descriptor": "Genomics", "descriptor_ui": "D023281", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Lung Neoplasms", "descriptor_ui": "D008175", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": false }, { "descriptor": "Neurosecretory Systems", "descriptor_ui": "D009490", "major_topic": false }, { "descriptor": "Nuclear Proteins", "descriptor_ui": "D009687", "major_topic": false }, { "descriptor": "Receptors, Notch", "descriptor_ui": "D051880", "major_topic": false }, { "descriptor": "Retinoblastoma Protein", "descriptor_ui": "D016160", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Small Cell Lung Carcinoma", "descriptor_ui": "D055752", "major_topic": false }, { "descriptor": "Tumor Protein p73", "descriptor_ui": "D000072160", "major_topic": false }, { "descriptor": "Tumor Suppressor Protein p53", "descriptor_ui": "D016159", "major_topic": false }, { "descriptor": "Tumor Suppressor Proteins", "descriptor_ui": "D025521", "major_topic": false } ], "publication": { "conference_name": null, "date": "2015 Aug 6", "date_precision": "day", "issue": "7563", "normalized_date": "2015-08-06", "pages": "47-53", "proceedings_title": null, "publisher": "", "title": "Nature", "volume": "524", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "Comprehensive genomic profiles of small cell lung cancer.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "An enzyme-responsive NIR nanosystem based on MEF was fabricated by surface functionalization of gold nanoparticles. Sensors based on this strategy are promising for enzyme detection in early diagnostic imaging and in vivo applications.", "classifications": [ { "id": "Fujita", "label": "Group Fujita", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Zhanghua", "last_name": "Zeng", "name": null }, { "creator_type": "author", "first_name": "Shin", "last_name": "Mizukami", "name": null }, { "creator_type": "author", "first_name": "Katsumasa", "last_name": "Fujita", "name": null }, { "creator_type": "author", "first_name": "Kazuya", "last_name": "Kikuchi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1039/c5sc01850a" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "29142724" } }, "mesh": [], "publication": { "conference_name": null, "date": "2015 Aug 1", "date_precision": "day", "issue": "8", "normalized_date": "2015-08-01", "pages": "4934-4939", "proceedings_title": null, "publisher": "", "title": "Chemical Science", "volume": "6", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "An enzyme-responsive metal-enhanced near-infrared fluorescence sensor based on functionalized gold nanoparticles††Electronic supplementary information (ESI) available: Detailed information on the synthetic routes to various ligands, characterization data, additional figures, schemes, tables and general experiment procedures are provided. See DOI: 10.1039/c5sc01850aClick here for additional data file.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "We disclose the development of a ratiometric fluorescent probe based on a benzophosphole P-oxide and its application for the detection of intracellular Na(+) ions. Excitation by visible light induced red emission from this probe in water, which was subjected to a hypsochromic shift upon complexation with Na(+). Based on this change, a ratiometric analysis enabled us to visualise changes in the Na(+) concentration in living mammalian cells.", "classifications": [ { "id": "Sato", "label": "Group Sato", "parent": "Tsuchiya", "type": "group" }, { "id": "Tsuchiya", "label": "Team Tsuchiya", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Masayasu", "last_name": "Taki", "name": null }, { "creator_type": "author", "first_name": "Hiroaki", "last_name": "Ogasawara", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Osaki", "name": null }, { "creator_type": "author", "first_name": "Aiko", "last_name": "Fukazawa", "name": null }, { "creator_type": "author", "first_name": "Yoshikatsu", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Kimi", "last_name": "Ogasawara", "name": null }, { "creator_type": "author", "first_name": "Tetsuya", "last_name": "Higashiyama", "name": null }, { "creator_type": "author", "first_name": "Shigehiro", "last_name": "Yamaguchi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1039/c5cc03547c" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "26110470" } }, "mesh": [ { "descriptor": "Cyclic P-Oxides", "descriptor_ui": "D003498", "major_topic": false }, { "descriptor": "Fluorescent Dyes", "descriptor_ui": "D005456", "major_topic": false }, { "descriptor": "HeLa Cells", "descriptor_ui": "D006367", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Ions", "descriptor_ui": "D007477", "major_topic": false }, { "descriptor": "Molecular Structure", "descriptor_ui": "D015394", "major_topic": false }, { "descriptor": "Oxides", "descriptor_ui": "D010087", "major_topic": false }, { "descriptor": "Sodium", "descriptor_ui": "D012964", "major_topic": false } ], "publication": { "conference_name": null, "date": "2015 Jul 28", "date_precision": "day", "issue": "59", "normalized_date": "2015-07-28", "pages": "11880-11883", "proceedings_title": null, "publisher": "", "title": "Chemical communications (Cambridge, England)", "volume": "51", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "A red-emitting ratiometric fluorescent probe based on a benzophosphole P-oxide scaffold for the detection of intracellular sodium ions.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Donor treatment with agonistic DR3 antibody induces selective expansion of Tregs and reduced activation of conventional T cells.T cells from DR3 antibody–treated donors result in reduced acute GVHD and preserved GVT effects.", "classifications": [ { "id": "Nishikii", "label": "Group Nishikii", "parent": "Shintaku", "type": "group" }, { "id": "Shintaku", "label": "Team Shintaku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Byung-Su", "last_name": "Kim", "name": null }, { "creator_type": "author", "first_name": "Hidekazu", "last_name": "Nishikii", "name": null }, { "creator_type": "author", "first_name": "Jeanette", "last_name": "Baker", "name": null }, { "creator_type": "author", "first_name": "Antonio", "last_name": "Pierini", "name": null }, { "creator_type": "author", "first_name": "Dominik", "last_name": "Schneidawind", "name": null }, { "creator_type": "author", "first_name": "Yuqiong", "last_name": "Pan", "name": null }, { "creator_type": "author", "first_name": "Andreas", "last_name": "Beilhack", "name": null }, { "creator_type": "author", "first_name": "Chung-Gyu", "last_name": "Park", "name": null }, { "creator_type": "author", "first_name": "Robert S.", "last_name": "Negrin", "name": null } ], "identifiers": { "doi": { "normalized": "10.1182/blood-2015-04-637587" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "26063163" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Antibodies", "descriptor_ui": "D000906", "major_topic": false }, { "descriptor": "Bone Marrow Transplantation", "descriptor_ui": "D016026", "major_topic": false }, { "descriptor": "CD4-Positive T-Lymphocytes", "descriptor_ui": "D015496", "major_topic": false }, { "descriptor": "Cytokines", "descriptor_ui": "D016207", "major_topic": false }, { "descriptor": "Disease Models, Animal", "descriptor_ui": "D004195", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Forkhead Transcription Factors", "descriptor_ui": "D051858", "major_topic": false }, { "descriptor": "Graft vs Host Disease", "descriptor_ui": "D006086", "major_topic": false }, { "descriptor": "Graft vs Tumor Effect", "descriptor_ui": "D020350", "major_topic": false }, { "descriptor": "Immunoglobulins", "descriptor_ui": "D007136", "major_topic": false }, { "descriptor": "Lymphoma, B-Cell", "descriptor_ui": "D016393", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred BALB C", "descriptor_ui": "D008807", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Microscopy, Fluorescence", "descriptor_ui": "D008856", "major_topic": false }, { "descriptor": "Receptors, Tumor Necrosis Factor, Member 25", "descriptor_ui": "D053219", "major_topic": false }, { "descriptor": "T-Lymphocytes, Regulatory", "descriptor_ui": "D050378", "major_topic": false }, { "descriptor": "Tissue Donors", "descriptor_ui": "D014019", "major_topic": false }, { "descriptor": "Transplantation, Homologous", "descriptor_ui": "D014184", "major_topic": false }, { "descriptor": "Tumor Cells, Cultured", "descriptor_ui": "D014407", "major_topic": false } ], "publication": { "conference_name": null, "date": "2015 Jul 23", "date_precision": "day", "issue": "4", "normalized_date": "2015-07-23", "pages": "546-557", "proceedings_title": null, "publisher": "", "title": "Blood", "volume": "126", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "Treatment with agonistic DR3 antibody results in expansion of donor Tregs and reduced graft-versus-host disease.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Elucidation of the cellular identity of neuronal precursors provides mechanistic insights into the development and pathophysiology of the nervous system. In the enteric nervous system (ENS), neurogenesis persists from midgestation to the postnatal period. Cellular mechanism underlying the long-term neurogenesis in the ENS has remained unclear. Using genetic fate mapping in mice, we show here that a subset of Schwann cell precursors (SCPs), which invades the gut alongside the extrinsic nerves, adopts a neuronal fate in the postnatal period and contributes to the ENS. We found SCP-derived neurogenesis in the submucosal region of the small intestine in the absence of vagal neural crest-derived ENS precursors. Under physiological conditions, SCPs comprised up to 20% of enteric neurons in the large intestine and gave rise mainly to restricted neuronal subtypes, calretinin-expressing neurons. Genetic ablation of Ret, the signaling receptor for glial cell line-derived neurotrophic factor, in SCPs caused colonic oligoganglionosis, indicating that SCP-derived neurogenesis is essential to ENS integrity. Identification of Schwann cells as a physiological neurogenic source provides novel insight into the development and disorders of neural crest-derived tissues. SIGNIFICANCE STATEMENT: Elucidating the cellular identity of neuronal precursors provides novel insights into development and function of the nervous system. The enteric nervous system (ENS) is innervated richly by extrinsic nerve fibers, but little is known about the significance of extrinsic innervation to the structural integrity of the ENS. This report reveals that a subset of Schwann cell precursors (SCPs), which invades the gut alongside the extrinsic nerves, adopts a neuronal fate and differentiates into specific neuronal subtypes. SCP-specific ablation of the Ret gene leads to colonic oligoganglionosis, demonstrating a crucial role of SCP-derived neurogenesis in ENS development. Cross-lineage differentiation capacity in SCPs suggests their potential involvement in the development and pathology of a wide variety of neural crest-derived cell types.", "classifications": [ { "id": "Enomoto", "label": "Group Enomoto", "parent": "Enomoto", "type": "group" }, { "id": "Enomoto", "label": "Team Enomoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Toshihiro", "last_name": "Uesaka", "name": null }, { "creator_type": "author", "first_name": "Mayumi", "last_name": "Nagashimada", "name": null }, { "creator_type": "author", "first_name": "Hideki", "last_name": "Enomoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1523/jneurosci.1239-15.2015" }, "pmcid": { "normalized": "PMC6605410" }, "pmid": { "normalized": "26156989" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Animals, Newborn", "descriptor_ui": "D000831", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Embryo, Mammalian", "descriptor_ui": "D004622", "major_topic": false }, { "descriptor": "Enteric Nervous System", "descriptor_ui": "D017615", "major_topic": false }, { "descriptor": "Glial Cell Line-Derived Neurotrophic Factor", "descriptor_ui": "D051100", "major_topic": false }, { "descriptor": "Glial Cell Line-Derived Neurotrophic Factor Receptors", "descriptor_ui": "D051097", "major_topic": false }, { "descriptor": "Hedgehog Proteins", "descriptor_ui": "D053823", "major_topic": false }, { "descriptor": "Homeodomain Proteins", "descriptor_ui": "D018398", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Transgenic", "descriptor_ui": "D008822", "major_topic": false }, { "descriptor": "Nerve Tissue Proteins", "descriptor_ui": "D009419", "major_topic": false }, { "descriptor": "Neurogenesis", "descriptor_ui": "D055495", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Proto-Oncogene Proteins c-ret", "descriptor_ui": "D051096", "major_topic": false }, { "descriptor": "Schwann Cells", "descriptor_ui": "D012583", "major_topic": false }, { "descriptor": "Stem Cells", "descriptor_ui": "D013234", "major_topic": false }, { "descriptor": "Transcription Factors", "descriptor_ui": "D014157", "major_topic": false }, { "descriptor": "Tyrosine 3-Monooxygenase", "descriptor_ui": "D014446", "major_topic": false }, { "descriptor": "Ubiquitin Thiolesterase", "descriptor_ui": "D043222", "major_topic": false } ], "publication": { "conference_name": null, "date": "2015 Jul 8", "date_precision": "day", "issue": "27", "normalized_date": "2015-07-08", "pages": "9879-9888", "proceedings_title": null, "publisher": "", "title": "The Journal of neuroscience : the official journal of the Society for Neuroscience", "volume": "35", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "Neuronal Differentiation in Schwann Cell Lineage Underlies Postnatal Neurogenesis in the Enteric Nervous System.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Three Raman probes of sphingomyelin (SM) were synthesized and evaluated for their applicability to imaging experiments. One probe containing a hydroxymethyl-1,3-butadiyne moiety in the polar head group showed strong scattering. The solid-state (2)H NMR spectra of this probe in oriented bilayer membrane revealed excellent compatibility with natural SM in phase behavior since the probe undergoes phase separation to form raft-like liquid ordered (Lo) domains in the raft-mimicking mixed bilayers.", "classifications": [ { "id": "Sodeoka", "label": "Group Sodeoka", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Jin", "last_name": "Cui", "name": null }, { "creator_type": "author", "first_name": "Shigeru", "last_name": "Matsuoka", "name": null }, { "creator_type": "author", "first_name": "Masanao", "last_name": "Kinoshita", "name": null }, { "creator_type": "author", "first_name": "Nobuaki", "last_name": "Matsumori", "name": null }, { "creator_type": "author", "first_name": "Fuminori", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Michio", "last_name": "Murata", "name": null }, { "creator_type": "author", "first_name": "Jun", "last_name": "Ando", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Yamakoshi", "name": null }, { "creator_type": "author", "first_name": "Kosuke", "last_name": "Dodo", "name": null }, { "creator_type": "author", "first_name": "Mikiko", "last_name": "Sodeoka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.bmc.2015.05.014" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "26026768" } }, "mesh": [ { "descriptor": "Alkynes", "descriptor_ui": "D000480", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cattle", "descriptor_ui": "D002417", "major_topic": false }, { "descriptor": "Lipid Bilayers", "descriptor_ui": "D008051", "major_topic": false }, { "descriptor": "Magnetic Resonance Spectroscopy", "descriptor_ui": "D009682", "major_topic": false }, { "descriptor": "Membrane Microdomains", "descriptor_ui": "D021962", "major_topic": false }, { "descriptor": "Molecular Mimicry", "descriptor_ui": "D018716", "major_topic": false }, { "descriptor": "Molecular Probes", "descriptor_ui": "D015335", "major_topic": false }, { "descriptor": "Phase Transition", "descriptor_ui": "D044367", "major_topic": false }, { "descriptor": "Phosphatidylcholines", "descriptor_ui": "D010713", "major_topic": false }, { "descriptor": "Sphingomyelins", "descriptor_ui": "D013109", "major_topic": false } ], "publication": { "conference_name": null, "date": "2015 Jul 1", "date_precision": "day", "issue": "13", "normalized_date": "2015-07-01", "pages": "2989-2994", "proceedings_title": null, "publisher": "", "title": "Bioorganic & medicinal chemistry", "volume": "23", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "Novel Raman-tagged sphingomyelin that closely mimics original raft-forming behavior.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Bismethylmercury sulfide (MeHg)2S has been found to be a detoxified metabolite of methylmercury (MeHg) that is produced by SH-SY5Y cells and in livers of rats exposed to MeHg. (MeHg)2S could be formed through the interactions between MeHg and sulfur species such as hydrogen sulfide (H2S or HS(-)), but the origin of its sulfur has not been fully identified. We herein examined the formation of (MeHg)2S through interactions between MeHg and persulfides, polysulfides, and protein preparations. Investigations using HPLC/atomic absorption spectrophotometry and EI-MS revealed that NaHS and Na2S4 react readily with MeHg to give (MeHg)2S, and similar results were found using GSH persulfide (GSSH) formed endogenously or generated enzymatically in vitro. (MeHg)2S was also formed by incubation of MeHg with liver and heart cytosolic fractions prepared from wild-type mice but not with those from mice lacking cystathionine gamma-lyase (CSE) that catalyzes the formation of cysteine persulfide. Consistent with this, (MeHg)2S was detected in a variety of tissues taken from wild-type mice intraperitoneally injected with MeHg in vivo but not in those from MeHg-injected CSE knockout mice. By separating liver fractions by column chromatography, we found numerous proteins that contain persulfides: one of the proteins was identified as being glutathione S-transferase pi 1. These results indicate that the formation of (MeHg)2S can be attributed to interactions between MeHg and endogenous free persulfide species, as well as protein-bound cysteine persulfide.", "classifications": [ { "id": "Akaike", "label": "Group Akaike", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yumi", "last_name": "Abiko", "name": null }, { "creator_type": "author", "first_name": "Eiko", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Isao", "last_name": "Ishii", "name": null }, { "creator_type": "author", "first_name": "Jon M.", "last_name": "Fukuto", "name": null }, { "creator_type": "author", "first_name": "Takaaki", "last_name": "Akaike", "name": null }, { "creator_type": "author", "first_name": "Yoshito", "last_name": "Kumagai", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/acs.chemrestox.5b00101" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "25874357" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cytosol", "descriptor_ui": "D003600", "major_topic": false }, { "descriptor": "Glutathione S-Transferase pi", "descriptor_ui": "D051549", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Liver", "descriptor_ui": "D008099", "major_topic": false }, { "descriptor": "Methylmercury Compounds", "descriptor_ui": "D008767", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Molecular Weight", "descriptor_ui": "D008970", "major_topic": false }, { "descriptor": "Recombinant Proteins", "descriptor_ui": "D011994", "major_topic": false }, { "descriptor": "Sulfides", "descriptor_ui": "D013440", "major_topic": false } ], "publication": { "conference_name": null, "date": "2015 Jun 15", "date_precision": "day", "issue": "6", "normalized_date": "2015-06-15", "pages": "1301-1306", "proceedings_title": null, "publisher": "", "title": "Chemical research in toxicology", "volume": "28", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "Involvement of reactive persulfides in biological bismethylmercury sulfide formation.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Single-cell mRNA sequencing (RNA-seq) methods have undergone rapid development in recent years, and transcriptome analysis of relevant cell populations at single-cell resolution has become a key research area of biomedical sciences. We here present single-cell mRNA 3-prime end sequencing (SC3-seq), a practical methodology based on PCR amplification followed by 3-prime-end enrichment for highly quantitative, parallel and cost-effective measurement of gene expression in single cells. The SC3-seq allows excellent quantitative measurement of mRNAs ranging from the 10,000-cell to 1-cell level, and accordingly, allows an accurate estimate of the transcript levels by a regression of the read counts of spike-in RNAs with defined copy numbers. The SC3-seq has clear advantages over other typical single-cell RNA-seq methodologies for the quantitative measurement of transcript levels and at a sequence depth required for the saturation of transcript detection. The SC3-seq distinguishes four distinct cell types in the peri-implantation mouse blastocysts. Furthermore, the SC3-seq reveals the heterogeneity in human-induced pluripotent stem cells (hiPSCs) cultured under on-feeder as well as feeder-free conditions, demonstrating a more homogeneous property of the feeder-free hiPSCs. We propose that SC3-seq might be used as a powerful strategy for single-cell transcriptome analysis in a broad range of investigations in biomedical sciences.", "classifications": [ { "id": "Yamamoto", "label": "Group Yamamoto", "parent": "Toyoshima", "type": "group" }, { "id": "Toyoshima", "label": "Team Toyoshima", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Tomonori", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Yukihiro", "last_name": "Yabuta", "name": null }, { "creator_type": "author", "first_name": "Ikuhiro", "last_name": "Okamoto", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Aramaki", "name": null }, { "creator_type": "author", "first_name": "Shihori", "last_name": "Yokobayashi", "name": null }, { "creator_type": "author", "first_name": "Kazuki", "last_name": "Kurimoto", "name": null }, { "creator_type": "author", "first_name": "Kiyotoshi", "last_name": "Sekiguchi", "name": null }, { "creator_type": "author", "first_name": "Masato", "last_name": "Nakagawa", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Mitinori", "last_name": "Saitou", "name": null } ], "identifiers": { "doi": { "normalized": "10.1093/nar/gkv134" }, "pmcid": { "normalized": "PMC4482058" }, "pmid": { "normalized": "25722368" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Blastocyst", "descriptor_ui": "D001755", "major_topic": false }, { "descriptor": "Gene Expression Profiling", "descriptor_ui": "D020869", "major_topic": false }, { "descriptor": "High-Throughput Nucleotide Sequencing", "descriptor_ui": "D059014", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Induced Pluripotent Stem Cells", "descriptor_ui": "D057026", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Sequence Analysis, RNA", "descriptor_ui": "D017423", "major_topic": false }, { "descriptor": "Single-Cell Analysis", "descriptor_ui": "D059010", "major_topic": true } ], "publication": { "conference_name": null, "date": "2015 May 19", "date_precision": "day", "issue": "9", "normalized_date": "2015-05-19", "pages": "e60", "proceedings_title": null, "publisher": "", "title": "Nucleic acids research", "volume": "43", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "SC3-seq: a method for highly parallel and quantitative measurement of single-cell gene expression.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Synthesis of a focused library is an important strategy to create novel modulators of specific classes of proteins. Compounds in a focused library are composed of a common core structure and different diversity structures. In this Account, we describe our design and synthesis of libraries focused on selective inhibitors of protein phosphatases (PPases). We considered that core structures having structural and electronic features similar to those of PPase substrates, phosphate esters, would be a reasonable choice. Therefore, we extracted core structures from natural products already identified as PPase inhibitors. Since many PPases share similar active-site structures, such phosphate-mimicking core structures should interact with many enzymes in the same family, and therefore the choice of diversity structures is pivotal both to increase the binding affinity and to achieve specificity for individual enzymes. Here we present case studies of application of focused libraries to obtain PPase inhibitors, covering the overall process from selection of core structures to identification and evaluation of candidates in the focused libraries. To synthesize a library focused on protein serine-threonine phosphatases (PPs), we chose norcantharidin as a core structure, because norcantharidin dicarboxylate shows a broad inhibition profile toward several PPs. From the resulting focused library, we identified a highly selective PP2B inhibitor, NCA-01. On the other hand, to find inhibitors of dual-specificity protein phosphatases (DSPs), we chose 3-acyltetronic acid extracted from natural product RK-682 as a core structure, because its structure resembles the transition state in the dephosphorylation reaction of DSPs. However, a highly selective inhibitor was not found in the resulting focused library. Furthermore, an inherent drawback of compounds having the highly acidic 3-acyltetronic acid as a core structure is very weak potency in cellulo, probably due to poor cell membrane permeability. Therefore, we next modified the core structure from acidic to neutral by transformation to the enamine derivative and constructed a second-generation focused library (RE derivatives). The resulting compounds showed dramatically improved cell membrane permeability and inhibitory selectivity and included VHR (vaccinia VH1-related)-selective RE12 and CDC25A/B (cell division cycle 25A/B)-selective RE44. These inhibitors act on target enzymes in cellulo and do not generate reactive oxygen species, which is a potential problem with quinoid-type inhibitors of CDC25s. The cellular activity of RE12 was further improved by replacement of the side chain to afford RE176, which showed more potent antiproliferative activity than RE12 against HeLa cells. The dramatic change of inhibitory selectivity obtained by core structure modification from 3-acyltetronic acid to its enamine derivative was associated with a change in the mode of action. Namely, RE derivatives were found to be noncompetitive inhibitors with respect to a small-molecular substrate of CDC25A/B, whereas RK-682 was a competitive inhibitor of VHR. We identified the binding site of RE derivatives on the CDC25A as a pocket adjacent to the active site; this appears to be a promising target site for development of further novel inhibitors of CDC25s.", "classifications": [ { "id": "Sodeoka", "label": "Group Sodeoka", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Go", "last_name": "Hirai", "name": null }, { "creator_type": "author", "first_name": "Mikiko", "last_name": "Sodeoka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/acs.accounts.5b00048" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "25894598" } }, "mesh": [ { "descriptor": "Biological Products", "descriptor_ui": "D001688", "major_topic": false }, { "descriptor": "Enzyme Inhibitors", "descriptor_ui": "D004791", "major_topic": false }, { "descriptor": "Molecular Structure", "descriptor_ui": "D015394", "major_topic": false }, { "descriptor": "Phosphoprotein Phosphatases", "descriptor_ui": "D010749", "major_topic": false }, { "descriptor": "Small Molecule Libraries", "descriptor_ui": "D054852", "major_topic": false }, { "descriptor": "Structure-Activity Relationship", "descriptor_ui": "D013329", "major_topic": false } ], "publication": { "conference_name": null, "date": "2015 May 19", "date_precision": "day", "issue": "5", "normalized_date": "2015-05-19", "pages": "1464-1473", "proceedings_title": null, "publisher": "", "title": "Accounts of chemical research", "volume": "48", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "Focused library with a core structure extracted from natural products and modified: application to phosphatase inhibitors and several biochemical findings.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Sulfhydration by a hydrogen sulfide anion and electrophile thiolation by reactive sulfur species (RSS) such as persulfides/polysulfides (e.g., R-S-SH/R-S-Sn-H(R)) are unique reactions in electrophilic signaling. Using 1,2-dihydroxynaphthalene-4-thioacetate (1,2-NQH2-SAc) as a precursor to 1,2-dihydroxynaphthalene-4-thiol (1,2-NQH2-SH) and a generator of reactive oxygen species (ROS), we demonstrate that protein thiols can be modified by a reactive sulfenic acid to form disulfide adducts that undergo rapid cleavage in the presence of glutathione (GSH). As expected, 1,2-NQH2-SAc is rapidly hydrolyzed and partially oxidized to yield 1,2-NQ-SH, resulting in a redox cycling reaction that produces ROS through a chemical disproportionation reaction. The sulfenic acid forms of 1,2-NQ-SH and 1,2-NQH2-SH were detected by derivatization experiments with dimedone. 1,2-NQH2-SOH modified Keap1 at Cys171 to produce a Keap1-S-S-1,2-NQH2 adduct. Subsequent exposure of A431 cells to 1,2-NQ or 1,2-NQH2-SAc caused an extensive chemical modification of cellular proteins in both cases. Protein adduction by 1,2-NQ through a thio ether (C-S-C) bond slowly declined through a GSH-dependent S-transarylation reaction, whereas that originating from 1,2-NQH2-SAc through a disulfide (C-S-S-C) bond was rapidly restored to the free protein thiol in the cells. Under these conditions, 1,2-NQH2-SAc activated Nrf2 and upregulated its target genes, which were enhanced by pretreatment with buthionine sulfoximine (BSO), to deplete cellular GSH. Pretreatment of catalase conjugated with poly(ethylene glycol) suppressed Nrf2 activation by 1,2-NQH2-SAc. These results suggest that RSS-mediated reversible electrophilic signaling takes place through sulfenic acids formation under oxidative stress.", "classifications": [ { "id": "Akaike", "label": "Group Akaike", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yasuhiro", "last_name": "Shinkai", "name": null }, { "creator_type": "author", "first_name": "Yumi", "last_name": "Abiko", "name": null }, { "creator_type": "author", "first_name": "Tomoaki", "last_name": "Ida", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Miura", "name": null }, { "creator_type": "author", "first_name": "Hidenao", "last_name": "Kakehashi", "name": null }, { "creator_type": "author", "first_name": "Isao", "last_name": "Ishii", "name": null }, { "creator_type": "author", "first_name": "Motohiro", "last_name": "Nishida", "name": null }, { "creator_type": "author", "first_name": "Tomohiro", "last_name": "Sawa", "name": null }, { "creator_type": "author", "first_name": "Takaaki", "last_name": "Akaike", "name": null }, { "creator_type": "author", "first_name": "Yoshito", "last_name": "Kumagai", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/tx500416y" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "25807370" } }, "mesh": [ { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Cysteine", "descriptor_ui": "D003545", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Intracellular Signaling Peptides and Proteins", "descriptor_ui": "D047908", "major_topic": false }, { "descriptor": "Kelch-Like ECH-Associated Protein 1", "descriptor_ui": "D000072019", "major_topic": false }, { "descriptor": "Naphthols", "descriptor_ui": "D009284", "major_topic": false }, { "descriptor": "Naphthoquinones", "descriptor_ui": "D009285", "major_topic": false }, { "descriptor": "NF-E2-Related Factor 2", "descriptor_ui": "D051267", "major_topic": false }, { "descriptor": "Oxidative Stress", "descriptor_ui": "D018384", "major_topic": true }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": true }, { "descriptor": "Sulfenic Acids", "descriptor_ui": "D013434", "major_topic": false }, { "descriptor": "Sulfhydryl Compounds", "descriptor_ui": "D013438", "major_topic": false }, { "descriptor": "Sulfur", "descriptor_ui": "D013455", "major_topic": false } ], "publication": { "conference_name": null, "date": "2015 May 18", "date_precision": "day", "issue": "5", "normalized_date": "2015-05-18", "pages": "838-847", "proceedings_title": null, "publisher": "", "title": "Chemical research in toxicology", "volume": "28", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "Reactive Sulfur Species-Mediated Activation of the Keap1-Nrf2 Pathway by 1,2-Naphthoquinone through Sulfenic Acids Formation under Oxidative Stress.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "IDH1 and IDH2 mutations occur frequently in acute myeloid leukemia (AML) and other cancers. The mutant isocitrate dehydrogenase (IDH) enzymes convert alpha-ketoglutarate (alpha-KG) to the oncometabolite 2-hydroxyglutarate (2-HG), which dysregulates a set of alpha-KG-dependent dioxygenases. To determine whether mutant IDH enzymes are valid targets for cancer therapy, we created a mouse model of AML in which mice were transplanted with nucleophosmin1 (NPM)(+/-) hematopoietic stem/progenitor cells cotransduced with four mutant genes (NPMc, IDH2/R140Q, DNMT3A/R882H, and FLT3/ITD), which often occur simultaneously in human AML patients. Conditional deletion of IDH2/R140Q blocked 2-HG production and maintenance of leukemia stem cells, resulting in survival of the AML mice. IDH2/R140Q was necessary for the engraftment or survival of NPMc(+) cells in vivo. Gene expression analysis indicated that NPMc increased expression of Hoxa9. IDH2/R140Q also increased the level of Meis1 and activated the hypoxia pathway in AML cells. IDH2/R140Q decreased the 5hmC modification and expression of some differentiation-inducing genes (Ebf1 and Spib). Taken together, our results indicated that IDH2 mutation is critical for the development and maintenance of AML stem-like cells, and they provided a preclinical justification for targeting mutant IDH enzymes as a strategy for anticancer therapy.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yoko", "last_name": "Ogawara", "name": null }, { "creator_type": "author", "first_name": "Takuo", "last_name": "Katsumoto", "name": null }, { "creator_type": "author", "first_name": "Yukiko", "last_name": "Aikawa", "name": null }, { "creator_type": "author", "first_name": "Yutaka", "last_name": "Shima", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Kagiyama", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Hironori", "last_name": "Matsunaga", "name": null }, { "creator_type": "author", "first_name": "Takahiko", "last_name": "Seki", "name": null }, { "creator_type": "author", "first_name": "Kazushi", "last_name": "Araki", "name": null }, { "creator_type": "author", "first_name": "Issay", "last_name": "Kitabayashi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1158/0008-5472.can-14-2200" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "25795706" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Hypoxia", "descriptor_ui": "D015687", "major_topic": false }, { "descriptor": "Gene Expression Regulation, Leukemic", "descriptor_ui": "D015973", "major_topic": false }, { "descriptor": "Homeodomain Proteins", "descriptor_ui": "D018398", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Isocitrate Dehydrogenase", "descriptor_ui": "D007521", "major_topic": false }, { "descriptor": "Leukemia, Myeloid, Acute", "descriptor_ui": "D015470", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mutation, Missense", "descriptor_ui": "D020125", "major_topic": false }, { "descriptor": "Myeloid Ecotropic Viral Integration Site 1 Protein", "descriptor_ui": "D000075064", "major_topic": false }, { "descriptor": "Neoplasm Proteins", "descriptor_ui": "D009363", "major_topic": false }, { "descriptor": "Neoplasm Transplantation", "descriptor_ui": "D009368", "major_topic": false }, { "descriptor": "Nuclear Proteins", "descriptor_ui": "D009687", "major_topic": false }, { "descriptor": "Nucleophosmin", "descriptor_ui": "D000090243", "major_topic": false }, { "descriptor": "Up-Regulation", "descriptor_ui": "D015854", "major_topic": false } ], "publication": { "conference_name": null, "date": "2015 May 15", "date_precision": "day", "issue": "10", "normalized_date": "2015-05-15", "pages": "2005-2016", "proceedings_title": null, "publisher": "", "title": "Cancer research", "volume": "75", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "IDH2 and NPM1 Mutations Cooperate to Activate Hoxa9/Meis1 and Hypoxia Pathways in Acute Myeloid Leukemia.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Germ cell specification is accompanied by epigenetic remodeling, the scale and specificity of which are unclear. Here, we quantitatively delineate chromatin dynamics during induction of mouse embryonic stem cells (ESCs) to epiblast-like cells (EpiLCs) and from there into primordial germ cell-like cells (PGCLCs), revealing large-scale reorganization of chromatin signatures including H3K27me3 and H3K9me2 patterns. EpiLCs contain abundant bivalent gene promoters characterized by low H3K27me3, indicating a state primed for differentiation. PGCLCs initially lose H3K4me3 from many bivalent genes but subsequently regain this mark with concomitant upregulation of H3K27me3, particularly at developmental regulatory genes. PGCLCs progressively lose H3K9me2, including at lamina-associated perinuclear heterochromatin, resulting in changes in nuclear architecture. T recruits H3K27ac to activate BLIMP1 and early mesodermal programs during PGCLC specification, which is followed by BLIMP1-mediated repression of a broad range of targets, possibly through recruitment and spreading of H3K27me3. These findings provide a foundation for reconstructing regulatory networks of the germline epigenome.", "classifications": [ { "id": "Yamamoto", "label": "Group Yamamoto", "parent": "Toyoshima", "type": "group" }, { "id": "Toyoshima", "label": "Team Toyoshima", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Kazuki", "last_name": "Kurimoto", "name": null }, { "creator_type": "author", "first_name": "Yukihiro", "last_name": "Yabuta", "name": null }, { "creator_type": "author", "first_name": "Katsuhiko", "last_name": "Hayashi", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Ohta", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Kiyonari", "name": null }, { "creator_type": "author", "first_name": "Tadahiro", "last_name": "Mitani", "name": null }, { "creator_type": "author", "first_name": "Yoshinobu", "last_name": "Moritoki", "name": null }, { "creator_type": "author", "first_name": "Kenjiro", "last_name": "Kohri", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Kimura", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Katou", "name": null }, { "creator_type": "author", "first_name": "Katsuhiko", "last_name": "Shirahige", "name": null }, { "creator_type": "author", "first_name": "Mitinori", "last_name": "Saitou", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.stem.2015.03.002" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "25800778" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Brachyury Protein", "descriptor_ui": "D000098908", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Chromatin Assembly and Disassembly", "descriptor_ui": "D042002", "major_topic": false }, { "descriptor": "Embryonic Germ Cells", "descriptor_ui": "D000066473", "major_topic": false }, { "descriptor": "Embryonic Stem Cells", "descriptor_ui": "D053595", "major_topic": false }, { "descriptor": "Epigenesis, Genetic", "descriptor_ui": "D044127", "major_topic": false }, { "descriptor": "Epigenetic Repression", "descriptor_ui": "D063185", "major_topic": false }, { "descriptor": "Epigenomics", "descriptor_ui": "D057890", "major_topic": false }, { "descriptor": "Fetal Proteins", "descriptor_ui": "D005326", "major_topic": false }, { "descriptor": "Histones", "descriptor_ui": "D006657", "major_topic": false }, { "descriptor": "Homeodomain Proteins", "descriptor_ui": "D018398", "major_topic": false }, { "descriptor": "Kruppel-Like Transcription Factors", "descriptor_ui": "D051741", "major_topic": false }, { "descriptor": "Methylation", "descriptor_ui": "D008745", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Positive Regulatory Domain I-Binding Factor 1", "descriptor_ui": "D000074462", "major_topic": false }, { "descriptor": "Protein Binding", "descriptor_ui": "D011485", "major_topic": false }, { "descriptor": "T-Box Domain Proteins", "descriptor_ui": "D020825", "major_topic": false }, { "descriptor": "Transcription Factors", "descriptor_ui": "D014157", "major_topic": false } ], "publication": { "conference_name": null, "date": "2015 May 7", "date_precision": "day", "issue": "5", "normalized_date": "2015-05-07", "pages": "517-532", "proceedings_title": null, "publisher": "", "title": "Cell stem cell", "volume": "16", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "Quantitative Dynamics of Chromatin Remodeling during Germ Cell Specification from Mouse Embryonic Stem Cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Tissue-level characterization of deformation dynamics is crucial for understanding organ morphogenetic mechanisms, especially the interhierarchical links among molecular activities, cellular behaviors and tissue/organ morphogenetic processes. Limb development is a well-studied topic in vertebrate organogenesis. Nevertheless, there is still little understanding of tissue-level deformation relative to molecular and cellular dynamics. This is mainly because live recording of detailed cell behaviors in whole tissues is technically difficult. To overcome this limitation, by applying a recently developed Bayesian approach, we here constructed tissue deformation maps for chick limb development with high precision, based on snapshot lineage tracing using dye injection. The precision of the constructed maps was validated with a clear statistical criterion. From the geometrical analysis of the map, we identified three characteristic tissue growth modes in the limb and showed that they are consistent with local growth factor activity and cell cycle length. In particular, we report that SHH signaling activity changes dynamically with developmental stage and strongly correlates with the dynamic shift in the tissue growth mode. We also found anisotropic tissue deformation along the proximal-distal axis. Morphogenetic simulation and experimental studies suggested that this directional tissue elongation, and not local growth, has the greatest impact on limb shaping. This result was supported by the novel finding that anisotropic tissue elongation along the proximal-distal axis occurs independently of cell proliferation. Our study marks a pivotal point for multi-scale system understanding in vertebrate development.", "classifications": [ { "id": "Morishita", "label": "Group Morishita", "parent": "Morishita", "type": "group" }, { "id": "Morishita", "label": "Team Morishita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yoshihiro", "last_name": "Morishita", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Kuroiwa", "name": null }, { "creator_type": "author", "first_name": "Takayuki", "last_name": "Suzuki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1242/dev.109728" }, "pmcid": { "normalized": "PMC4419272" }, "pmid": { "normalized": "25858459" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Anisotropy", "descriptor_ui": "D016880", "major_topic": false }, { "descriptor": "Bayes Theorem", "descriptor_ui": "D001499", "major_topic": false }, { "descriptor": "Biomechanical Phenomena", "descriptor_ui": "D001696", "major_topic": false }, { "descriptor": "Cell Lineage", "descriptor_ui": "D019070", "major_topic": false }, { "descriptor": "Chick Embryo", "descriptor_ui": "D002642", "major_topic": false }, { "descriptor": "Computer Simulation", "descriptor_ui": "D003198", "major_topic": false }, { "descriptor": "Extremities", "descriptor_ui": "D005121", "major_topic": false }, { "descriptor": "Hedgehog Proteins", "descriptor_ui": "D053823", "major_topic": false }, { "descriptor": "Models, Biological", "descriptor_ui": "D008954", "major_topic": true }, { "descriptor": "Organogenesis", "descriptor_ui": "D038081", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false } ], "publication": { "conference_name": null, "date": "2015 May 1", "date_precision": "day", "issue": "9", "normalized_date": "2015-05-01", "pages": "1672-1683", "proceedings_title": null, "publisher": "", "title": "Development (Cambridge, England)", "volume": "142", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "Quantitative analysis of tissue deformation dynamics reveals three characteristic growth modes and globally aligned anisotropic tissue deformation during chick limb development.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The filamentous cyanobacterium, Anabaena sp. PCC 7120, is one of the simplest models of a multicellular system showing cellular differentiation. In nitrogen-deprived culture, undifferentiated vegetative cells differentiate into heterocysts at ~10-cell intervals along the cellular filament. As undifferentiated cells divide, the number of cells between heterocysts (segment length) increases, and a new heterocyst appears in the intermediate region. To understand how the heterocyst pattern is formed and maintained, we constructed a one-dimensional cellular automaton (CA) model of the heterocyst pattern formation. The dynamics of vegetative cells is modeled by a stochastic transition process including cell division, differentiation and increase of cell age (maturation). Cell division and differentiation depend on the time elapsed after the last cell division, the \"cell age\". The model dynamics was mathematically analyzed by a two-step Markov approximation. In the first step, we determined steady state of cell age distribution among vegetative cell population. In the second step, we determined steady state distribution of segment length among segment population. The analytical solution was consistent with the results of numerical simulations. We then compared the analytical solution with the experimental data, and quantitatively estimated the immeasurable intercellular kinetics. We found that differentiation is initially independent of cellular maturation, but becomes dependent on maturation as the pattern formation evolves. Our mathematical model and analysis enabled us to quantify the internal cellular dynamics at various stages of the heterocyst pattern formation.", "classifications": [ { "id": "Mochizuki", "label": "Group Mochizuki", "parent": "Eiraku", "type": "group" }, { "id": "Eiraku", "label": "Team Eiraku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Jun-ichi", "last_name": "Ishihara", "name": null }, { "creator_type": "author", "first_name": "Masashi", "last_name": "Tachikawa", "name": null }, { "creator_type": "author", "first_name": "Hideo", "last_name": "Iwasaki", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Mochizuki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.jtbi.2015.01.034" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "25665721" } }, "mesh": [ { "descriptor": "Cell Division", "descriptor_ui": "D002455", "major_topic": false }, { "descriptor": "Cell Lineage", "descriptor_ui": "D019070", "major_topic": false }, { "descriptor": "Cellular Senescence", "descriptor_ui": "D016922", "major_topic": false }, { "descriptor": "Computer Simulation", "descriptor_ui": "D003198", "major_topic": false }, { "descriptor": "Cyanobacteria", "descriptor_ui": "D000458", "major_topic": false }, { "descriptor": "Green Fluorescent Proteins", "descriptor_ui": "D049452", "major_topic": false }, { "descriptor": "Kinetics", "descriptor_ui": "D007700", "major_topic": false }, { "descriptor": "Markov Chains", "descriptor_ui": "D008390", "major_topic": false }, { "descriptor": "Models, Biological", "descriptor_ui": "D008954", "major_topic": true }, { "descriptor": "Reproducibility of Results", "descriptor_ui": "D015203", "major_topic": false }, { "descriptor": "Time Factors", "descriptor_ui": "D013997", "major_topic": false }, { "descriptor": "Time-Lapse Imaging", "descriptor_ui": "D059008", "major_topic": false }, { "descriptor": "Transcription, Genetic", "descriptor_ui": "D014158", "major_topic": false }, { "descriptor": "Video Recording", "descriptor_ui": "D014741", "major_topic": false } ], "publication": { "conference_name": null, "date": "2015 Apr 21", "date_precision": "day", "issue": "", "normalized_date": "2015-04-21", "pages": "9-23", "proceedings_title": null, "publisher": "", "title": "Journal of theoretical biology", "volume": "371", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "Mathematical study of pattern formation accompanied by heterocyst differentiation in multicellular cyanobacterium.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "We examined the mechanism of our previously reported aminotrifluoromethylation reaction, which proceeds via intramolecular cyclization of alkenylamines in the presence of the combination of copper catalyst and Togni reagent (1). Kinetic studies revealed that the initial rate of the reaction was first order with respect to Togni reagent and CuI, as well as the substrate. Changes of the (19)F NMR chemical shift of Togni reagent during the reaction suggested the existence of a dynamic equilibrium involving coordination of not only Togni reagent, but also the substrate amine and the product aziridine to copper. ESI-MS analysis provided evidence of involvement of reactive Cu(II) intermediates in the catalytic cycle. Overall, our results indicate that the reaction proceeds at the hypervalent iodine moiety of Togni reagent, which is activated by Cu(II) species acting as a Lewis acid catalyst. On the basis of these mechanistic considerations, we developed an efficient synthesis of trifluoromethylated pyrrolidine derivatives. This transformation exhibited a remarkable rate enhancement upon addition of Et3N.", "classifications": [ { "id": "Sodeoka", "label": "Group Sodeoka", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Shintaro", "last_name": "Kawamura", "name": null }, { "creator_type": "author", "first_name": "Hiromichi", "last_name": "Egami", "name": null }, { "creator_type": "author", "first_name": "Mikiko", "last_name": "Sodeoka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/jacs.5b02046" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "25798656" } }, "mesh": [ { "descriptor": "Alkenes", "descriptor_ui": "D000475", "major_topic": false }, { "descriptor": "Amines", "descriptor_ui": "D000588", "major_topic": false }, { "descriptor": "Catalysis", "descriptor_ui": "D002384", "major_topic": false }, { "descriptor": "Chemistry Techniques, Synthetic", "descriptor_ui": "D060326", "major_topic": false }, { "descriptor": "Cyclization", "descriptor_ui": "D003500", "major_topic": false }, { "descriptor": "Fluorocarbons", "descriptor_ui": "D005466", "major_topic": false }, { "descriptor": "Kinetics", "descriptor_ui": "D007700", "major_topic": false }, { "descriptor": "Methylation", "descriptor_ui": "D008745", "major_topic": false }, { "descriptor": "Pyrrolidines", "descriptor_ui": "D011759", "major_topic": false } ], "publication": { "conference_name": null, "date": "2015 Apr 15", "date_precision": "day", "issue": "14", "normalized_date": "2015-04-15", "pages": "4865-4873", "proceedings_title": null, "publisher": "", "title": "Journal of the American Chemical Society", "volume": "137", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "Aminotrifluoromethylation of olefins via cyclic amine formation: mechanistic study and application to synthesis of trifluoromethylated pyrrolidines.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "In patients with obstructive sleep apnea, airway obstruction during sleep produces hypercapnia, which in turn activates respiratory muscles that pump air into the lungs (e.g., the diaphragm) and that dilate and stabilize the upper airway (e.g., the genioglossus). We hypothesized that these responses are facilitated by glutamatergic neurons in the parabrachial complex (PB) that respond to hypercapnia and project to premotor and motor neurons that innervate the diaphragm and genioglossus muscles. To test this hypothesis, we combined c-Fos immunohistochemistry with in situ hybridization for vGluT2 or GAD67 or with retrograde tracing from the ventrolateral medullary region that contains phrenic premotor neurons, the phrenic motor nucleus in the C3-C5 spinal ventral horn, or the hypoglossal motor nucleus. We found that hypercapnia (10% CO2 for 2 hours) activated c-Fos expression in neurons in the external lateral, lateral crescent (PBcr), and Kolliker-Fuse (KF) PB subnuclei and that most of these neurons were glutamatergic and virtually none gamma-aminobutyric acidergic. Numerous CO2 -responsive neurons in the KF and PBcr were labeled after retrograde tracer injection into the ventrolateral medulla or hypoglossal motor nuclei, and in the KF after injections into the spinal cord, making them candidates for mediating respiratory-facilitatory and upper-airway-stabilizing effects of hypercapnia.", "classifications": [ { "id": "Yokota", "label": "Group Yokota", "parent": "Enomoto", "type": "group" }, { "id": "Enomoto", "label": "Team Enomoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Shigefumi", "last_name": "Yokota", "name": null }, { "creator_type": "author", "first_name": "Satvinder", "last_name": "Kaur", "name": null }, { "creator_type": "author", "first_name": "Veronique G.", "last_name": "VanderHorst", "name": null }, { "creator_type": "author", "first_name": "Clifford B.", "last_name": "Saper", "name": null }, { "creator_type": "author", "first_name": "Nancy L.", "last_name": "Chamberlin", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/cne.23720" }, "pmcid": { "normalized": "PMC4329052" }, "pmid": { "normalized": "25424719" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Calcitonin Gene-Related Peptide", "descriptor_ui": "D015740", "major_topic": false }, { "descriptor": "Cholera Toxin", "descriptor_ui": "D002772", "major_topic": false }, { "descriptor": "Glutamate Decarboxylase", "descriptor_ui": "D005968", "major_topic": false }, { "descriptor": "Glutamic Acid", "descriptor_ui": "D018698", "major_topic": false }, { "descriptor": "Hypercapnia", "descriptor_ui": "D006935", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Motor Neurons", "descriptor_ui": "D009046", "major_topic": false }, { "descriptor": "Neural Pathways", "descriptor_ui": "D009434", "major_topic": false }, { "descriptor": "Parabrachial Nucleus", "descriptor_ui": "D065823", "major_topic": false }, { "descriptor": "Proto-Oncogene Proteins c-fos", "descriptor_ui": "D016760", "major_topic": false }, { "descriptor": "Respiration", "descriptor_ui": "D012119", "major_topic": false }, { "descriptor": "Vesicular Glutamate Transport Protein 2", "descriptor_ui": "D050599", "major_topic": false } ], "publication": { "conference_name": null, "date": "2015 Apr 15", "date_precision": "day", "issue": "6", "normalized_date": "2015-04-15", "pages": "907-920", "proceedings_title": null, "publisher": "", "title": "The Journal of comparative neurology", "volume": "523", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "Respiratory-related outputs of glutamatergic, hypercapnia-responsive parabrachial neurons in mice.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "As the quintessential reprogramming model, OCT3/4, SOX2, KLF4, and c-MYC re-wire somatic cells to achieve induced pluripotency. Yet, subtle differences in methodology confound comparative studies of reprogramming mechanisms. Employing transposons, we systematically assessed cellular and molecular hallmarks of mouse somatic cell reprogramming by various polycistronic cassettes. Reprogramming responses varied in the extent of initiation and stabilization of transgene-independent pluripotency. Notably, the cassettes employed one of two KLF4 variants, differing only by nine N-terminal amino acids, which generated dissimilar protein stoichiometry. Extending the shorter variant by nine N-terminal amino acids or augmenting stoichiometry by KLF4 supplementation rescued both protein levels and phenotypic disparities, implicating a threshold in determining reprogramming outcomes. Strikingly, global gene expression patterns elicited by published polycistronic cassettes diverged according to each KLF4 variant. Our data expose a Klf4 reference cDNA variation that alters polycistronic factor stoichiometry, predicts reprogramming hallmarks, and guides comparison of compatible public data sets.", "classifications": [ { "id": "Yamamoto", "label": "Group Yamamoto", "parent": "Toyoshima", "type": "group" }, { "id": "Toyoshima", "label": "Team Toyoshima", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Shin-Il", "last_name": "Kim", "name": null }, { "creator_type": "author", "first_name": "Fabian", "last_name": "Oceguera-Yanez", "name": null }, { "creator_type": "author", "first_name": "Ryoko", "last_name": "Hirohata", "name": null }, { "creator_type": "author", "first_name": "Sara", "last_name": "Linker", "name": null }, { "creator_type": "author", "first_name": "Keisuke", "last_name": "Okita", "name": null }, { "creator_type": "author", "first_name": "Yasuhiro", "last_name": "Yamada", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Yamanaka", "name": null }, { "creator_type": "author", "first_name": "Knut", "last_name": "Woltjen", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.stemcr.2015.02.004" }, "pmcid": { "normalized": "PMC4400650" }, "pmid": { "normalized": "25772473" } }, "mesh": [ { "descriptor": "Alternative Splicing", "descriptor_ui": "D017398", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Cellular Reprogramming", "descriptor_ui": "D065150", "major_topic": false }, { "descriptor": "DNA Transposable Elements", "descriptor_ui": "D004251", "major_topic": false }, { "descriptor": "Gene Expression", "descriptor_ui": "D015870", "major_topic": false }, { "descriptor": "Gene Expression Regulation", "descriptor_ui": "D005786", "major_topic": false }, { "descriptor": "Gene Targeting", "descriptor_ui": "D018390", "major_topic": false }, { "descriptor": "Kruppel-Like Factor 4", "descriptor_ui": "D000090062", "major_topic": false }, { "descriptor": "Kruppel-Like Transcription Factors", "descriptor_ui": "D051741", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Phenotype", "descriptor_ui": "D010641", "major_topic": false }, { "descriptor": "Pluripotent Stem Cells", "descriptor_ui": "D039904", "major_topic": false }, { "descriptor": "Protein Interaction Domains and Motifs", "descriptor_ui": "D054730", "major_topic": false }, { "descriptor": "Protein Isoforms", "descriptor_ui": "D020033", "major_topic": false } ], "publication": { "conference_name": null, "date": "2015 Apr 14", "date_precision": "day", "issue": "4", "normalized_date": "2015-04-14", "pages": "727-743", "proceedings_title": null, "publisher": "", "title": "Stem cell reports", "volume": "4", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "KLF4 N-terminal variance modulates induced reprogramming to pluripotency.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Phase separation in lipid rafts has been observed with fluorescently labeled lipids, but they are often excluded from the ordered domain because of the steric effect of the bulky fluorophore on lipid packing, making it difficult to analyze the interior of the raft domain. Here, we synthesized an analog of sphingomyelin tagged with a small Raman active diyne moiety, which provides high chemical selectivity without affecting the membrane properties. Raman microscopy successfully visualized, at single lipid-layer sensitivity, a heterogeneous spatial distribution of this probe within raft-like ordered domains, which was different from the generally accepted raft model. This approach provides both chemical selectivity and quantitative imaging capability and is useful for functional studies of lipid rafts.", "classifications": [ { "id": "Fujita", "label": "Group Fujita", "parent": "Fujita", "type": "group" }, { "id": "Sodeoka", "label": "Group Sodeoka", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Jun", "last_name": "Ando", "name": null }, { "creator_type": "author", "first_name": "Masanao", "last_name": "Kinoshita", "name": null }, { "creator_type": "author", "first_name": "Jin", "last_name": "Cui", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Yamakoshi", "name": null }, { "creator_type": "author", "first_name": "Kosuke", "last_name": "Dodo", "name": null }, { "creator_type": "author", "first_name": "Katsumasa", "last_name": "Fujita", "name": null }, { "creator_type": "author", "first_name": "Michio", "last_name": "Murata", "name": null }, { "creator_type": "author", "first_name": "Mikiko", "last_name": "Sodeoka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1073/pnas.1418088112" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "25825736" } }, "mesh": [ { "descriptor": "Cholesterol", "descriptor_ui": "D002784", "major_topic": false }, { "descriptor": "Membrane Microdomains", "descriptor_ui": "D021962", "major_topic": false }, { "descriptor": "Membranes, Artificial", "descriptor_ui": "D008567", "major_topic": true }, { "descriptor": "Microscopy, Confocal", "descriptor_ui": "D018613", "major_topic": false }, { "descriptor": "Molecular Structure", "descriptor_ui": "D015394", "major_topic": false }, { "descriptor": "Phosphatidylcholines", "descriptor_ui": "D010713", "major_topic": false }, { "descriptor": "Reproducibility of Results", "descriptor_ui": "D015203", "major_topic": false }, { "descriptor": "Spectrum Analysis, Raman", "descriptor_ui": "D013059", "major_topic": false }, { "descriptor": "Sphingomyelins", "descriptor_ui": "D013109", "major_topic": false }, { "descriptor": "Unilamellar Liposomes", "descriptor_ui": "D053835", "major_topic": false } ], "publication": { "conference_name": null, "date": "2015 Apr 14", "date_precision": "day", "issue": "15", "normalized_date": "2015-04-14", "pages": "4558-4563", "proceedings_title": null, "publisher": "", "title": "Proceedings of the National Academy of Sciences of the United States of America", "volume": "112", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "Sphingomyelin distribution in lipid rafts of artificial monolayer membranes visualized by Raman microscopy.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Reduced expression of microRNA122 (miR122), a liver-specific microRNA, is frequent in hepatocellular carcinoma (HCC). However, its biological significances remain poorly understood. Because deregulated amino acid levels in cancers can affect their biological behavior, we determined the amino acid levels in miR122-silenced mouse liver tissues, in which intracellular arginine levels were significantly increased. The increased intracellular arginine levels were through upregulation of the solute carrier family 7 (SLC7A1), a transporter of arginine and a direct target of miR122. Arginine is the substrate for nitric oxide (NO) synthetase, and intracellular NO levels were increased in miR122-silenced HCC cells, with increased resistance to sorafenib, a multikinase inhibitor. Conversely, maintenance of the miR122-silenced HCC cells in arginine-depleted culture media, as well as overexpression of miR122 in miR122-low-expressing HCC cells, reversed these effects and rendered the cells more sensitive to sorafenib. Using a reporter knock-in construct, chemical compounds were screened, and Wee1 kinase inhibitor was identified as upregulators of miR122 transcription, which increased the sensitivity of the cells to sorafenib. These results provide an insight into sorafenib resistance in miR122-low HCC, and suggest that arginine depletion or a combination of sorafenib with the identified compound may provide promising approaches to managing this HCC subset.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Takahiro", "last_name": "Kishikawa", "name": null }, { "creator_type": "author", "first_name": "Motoyuki", "last_name": "Otsuka", "name": null }, { "creator_type": "author", "first_name": "Poh Seng", "last_name": "Tan", "name": null }, { "creator_type": "author", "first_name": "Motoko", "last_name": "Ohno", "name": null }, { "creator_type": "author", "first_name": "Xiaochen", "last_name": "Sun", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Yoshikawa", "name": null }, { "creator_type": "author", "first_name": "Chikako", "last_name": "Shibata", "name": null }, { "creator_type": "author", "first_name": "Akemi", "last_name": "Takata", "name": null }, { "creator_type": "author", "first_name": "Kentaro", "last_name": "Kojima", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Takehana", "name": null }, { "creator_type": "author", "first_name": "Maki", "last_name": "Ohishi", "name": null }, { "creator_type": "author", "first_name": "Sana", "last_name": "Ota", "name": null }, { "creator_type": "author", "first_name": "Tomoyuki", "last_name": "Noyama", "name": null }, { "creator_type": "author", "first_name": "Yuji", "last_name": "Kondo", "name": null }, { "creator_type": "author", "first_name": "Masaya", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Yujin", "last_name": "Hoshida", "name": null }, { "creator_type": "author", "first_name": "Kazuhiko", "last_name": "Koike", "name": null } ], "identifiers": { "doi": { "normalized": "10.18632/oncotarget.3234" }, "pmcid": { "normalized": "PMC4480756" }, "pmid": { "normalized": "25826076" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Apoptosis", "descriptor_ui": "D017209", "major_topic": false }, { "descriptor": "Arginine", "descriptor_ui": "D001120", "major_topic": false }, { "descriptor": "Carcinoma, Hepatocellular", "descriptor_ui": "D006528", "major_topic": false }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Drug Resistance, Neoplasm", "descriptor_ui": "D019008", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Liver Neoplasms", "descriptor_ui": "D008113", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Transgenic", "descriptor_ui": "D008822", "major_topic": false }, { "descriptor": "MicroRNAs", "descriptor_ui": "D035683", "major_topic": false }, { "descriptor": "Niacinamide", "descriptor_ui": "D009536", "major_topic": false }, { "descriptor": "Phenylurea Compounds", "descriptor_ui": "D010671", "major_topic": false }, { "descriptor": "Sorafenib", "descriptor_ui": "D000077157", "major_topic": false } ], "publication": { "conference_name": null, "date": "2015 Apr 10", "date_precision": "day", "issue": "10", "normalized_date": "2015-04-10", "pages": "8339-8352", "proceedings_title": null, "publisher": "", "title": "Oncotarget", "volume": "6", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "Decreased miR122 in hepatocellular carcinoma leads to chemoresistance with increased arginine.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Myosin is a mechano-enzyme that hydrolyzes ATP in order to move unidirectionally along actin filaments. Here we show by single molecule imaging that myosin V motion can be activated by local heat. We constructed a dark-field microscopy that included optical tweezers to monitor 80 nm gold nanoparticles (GNP) bound to single myosin V molecules with nanometer and submillisecond accuracy. We observed 34 nm processive steps along actin filaments like those seen when using 200 nm polystyrene beads (PB) but dwell times (ATPase activity) that were 4.5 times faster. Further, by using DNA nanotechnology (DNA origami) and myosin V as a nanometric thermometer, the temperature gradient surrounding optically trapped GNP could be estimated with nanometer accuracy. We propose our single molecule measurement system should advance quantitative analysis of the thermal control of biological and artificial systems like nanoscale thermal ratchet motors.", "classifications": [ { "id": "Iwaki", "label": "Group Iwaki", "parent": "Toyoshima", "type": "group" }, { "id": "Toyoshima", "label": "Team Toyoshima", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Mitsuhiro", "last_name": "Iwaki", "name": null }, { "creator_type": "author", "first_name": "Atsuko H.", "last_name": "Iwane", "name": null }, { "creator_type": "author", "first_name": "Keigo", "last_name": "Ikezaki", "name": null }, { "creator_type": "author", "first_name": "Toshio", "last_name": "Yanagida", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/nl5049059" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "25736894" } }, "mesh": [ { "descriptor": "DNA", "descriptor_ui": "D004247", "major_topic": false }, { "descriptor": "Gold", "descriptor_ui": "D006046", "major_topic": false }, { "descriptor": "Hot Temperature", "descriptor_ui": "D006358", "major_topic": false }, { "descriptor": "Materials Testing", "descriptor_ui": "D008422", "major_topic": false }, { "descriptor": "Metal Nanoparticles", "descriptor_ui": "D053768", "major_topic": false }, { "descriptor": "Molecular Imaging", "descriptor_ui": "D057054", "major_topic": false }, { "descriptor": "Molecular Motor Proteins", "descriptor_ui": "D020409", "major_topic": false }, { "descriptor": "Molecular Probe Techniques", "descriptor_ui": "D015336", "major_topic": false }, { "descriptor": "Myosins", "descriptor_ui": "D009218", "major_topic": false }, { "descriptor": "Optical Tweezers", "descriptor_ui": "D052898", "major_topic": true }, { "descriptor": "Temperature", "descriptor_ui": "D013696", "major_topic": false }, { "descriptor": "Thermography", "descriptor_ui": "D013817", "major_topic": false } ], "publication": { "conference_name": null, "date": "2015 Apr 8", "date_precision": "day", "issue": "4", "normalized_date": "2015-04-08", "pages": "2456-2461", "proceedings_title": null, "publisher": "", "title": "Nano letters", "volume": "15", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "Local heat activation of single myosins based on optical trapping of gold nanoparticles.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Electron-donating aryl groups were attached to electron-accepting benzophosphole skeletons. Among several derivatives thus prepared, one benzophosphole oxide was particularly interesting, as it retained high fluorescence quantum yields even in polar and protic solvents. This phosphole-based compound exhibited a drastic color change of its fluorescence spectrum as a function of the solvent polarity, while the absorption spectra remained virtually unchanged. Capitalizing on these features, this phosphole-based compound was used to stain adipocytes, in which the polarity of subcellular compartments could then be discriminated on the basis of the color change of the fluorescence emission.", "classifications": [ { "id": "Sato", "label": "Group Sato", "parent": "Tsuchiya", "type": "group" }, { "id": "Tsuchiya", "label": "Team Tsuchiya", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Eriko", "last_name": "Yamaguchi", "name": null }, { "creator_type": "author", "first_name": "Chenguang", "last_name": "Wang", "name": null }, { "creator_type": "author", "first_name": "Aiko", "last_name": "Fukazawa", "name": null }, { "creator_type": "author", "first_name": "Masayasu", "last_name": "Taki", "name": null }, { "creator_type": "author", "first_name": "Yoshikatsu", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Taeko", "last_name": "Sasaki", "name": null }, { "creator_type": "author", "first_name": "Minako", "last_name": "Ueda", "name": null }, { "creator_type": "author", "first_name": "Narie", "last_name": "Sasaki", "name": null }, { "creator_type": "author", "first_name": "Tetsuya", "last_name": "Higashiyama", "name": null }, { "creator_type": "author", "first_name": "Shigehiro", "last_name": "Yamaguchi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/anie.201500229" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "25740735" } }, "mesh": [ { "descriptor": "3T3-L1 Cells", "descriptor_ui": "D041721", "major_topic": false }, { "descriptor": "Adipocytes", "descriptor_ui": "D017667", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Benzene Derivatives", "descriptor_ui": "D001555", "major_topic": false }, { "descriptor": "Electrons", "descriptor_ui": "D004583", "major_topic": false }, { "descriptor": "Fluorescent Dyes", "descriptor_ui": "D005456", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Optical Imaging", "descriptor_ui": "D061848", "major_topic": false }, { "descriptor": "Organophosphorus Compounds", "descriptor_ui": "D009943", "major_topic": false }, { "descriptor": "Oxides", "descriptor_ui": "D010087", "major_topic": false }, { "descriptor": "Spectrometry, Fluorescence", "descriptor_ui": "D013050", "major_topic": false } ], "publication": { "conference_name": null, "date": "2015 Apr 7", "date_precision": "day", "issue": "15", "normalized_date": "2015-04-07", "pages": "4539-4543", "proceedings_title": null, "publisher": "", "title": "Angewandte Chemie (International ed. in English)", "volume": "54", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "Environment-sensitive fluorescent probe: a benzophosphole oxide with an electron-donating substituent.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Hemozoin, the 'malaria pigment', is engulfed by phagocytic cells, such as macrophages, during malaria infection. This biocrystalline substance is difficult to degrade and often accumulates in phagocytes. The macrophage response to hemozoin relates to the severity of the disease and the potential for malaria-related disease complications. In this study we have used Raman spectroscopy as a label-free method to investigate the biochemical changes occurring in macrophages during the first few hours of hemozoin uptake. We found a number of distinct spectral groups, spectrally or spatially related to the presence of the hemozoin inside the cell. Intracellular hemozoin was spectrally identical to extracellular hemozoin, regardless of the location in the cell. A small proportion of hemozoin was found to be associated with lipid-based components, consistent with the uptake of hemozoin into vesicles such as phagosomes and lysosomes. The spatial distribution of the hemozoin was observed to be inhomogeneous, and its presence largely excluded that of proteins and lipids, demonstrating that cells were not able to break down the biocrystals on the time scales studied here. These results show that Raman imaging can be used to answer some of the open questions regarding the role of hemozoin in the immune response. How different combinations of hemozoin and other molecules are treated by macrophages, whether hemozoin can be broken down by the cell, and more importantly, which co-factors or products are involved in the subsequent cell reaction are the expected issues to be elucidated by this technique.", "classifications": [ { "id": "Fujita", "label": "Group Fujita", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Alison J.", "last_name": "Hobro", "name": null }, { "creator_type": "author", "first_name": "Nicolas", "last_name": "Pavillon", "name": null }, { "creator_type": "author", "first_name": "Katsumasa", "last_name": "Fujita", "name": null }, { "creator_type": "author", "first_name": "Muge", "last_name": "Ozkan", "name": null }, { "creator_type": "author", "first_name": "Cevayir", "last_name": "Coban", "name": null }, { "creator_type": "author", "first_name": "Nicholas I.", "last_name": "Smith", "name": null } ], "identifiers": { "doi": { "normalized": "10.1039/c4an01850h" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "25646175" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Hemeproteins", "descriptor_ui": "D006420", "major_topic": false }, { "descriptor": "Lipid Metabolism", "descriptor_ui": "D050356", "major_topic": false }, { "descriptor": "Lysosomes", "descriptor_ui": "D008247", "major_topic": false }, { "descriptor": "Macrophages", "descriptor_ui": "D008264", "major_topic": false }, { "descriptor": "Malaria", "descriptor_ui": "D008288", "major_topic": true }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Molecular Imaging", "descriptor_ui": "D057054", "major_topic": true }, { "descriptor": "Phagosomes", "descriptor_ui": "D010588", "major_topic": false }, { "descriptor": "Pigments, Biological", "descriptor_ui": "D010860", "major_topic": false }, { "descriptor": "Principal Component Analysis", "descriptor_ui": "D025341", "major_topic": false }, { "descriptor": "Protein Transport", "descriptor_ui": "D021381", "major_topic": false }, { "descriptor": "Spectrum Analysis, Raman", "descriptor_ui": "D013059", "major_topic": true } ], "publication": { "conference_name": null, "date": "2015 Apr 7", "date_precision": "day", "issue": "7", "normalized_date": "2015-04-07", "pages": "2350-2359", "proceedings_title": null, "publisher": "", "title": "The Analyst", "volume": "140", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "Label-free Raman imaging of the macrophage response to the malaria pigment hemozoin.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Condensin I is a five-subunit protein complex that plays a central role in mitotic chromosome assembly and segregation in eukaryotes. To dissect its mechanism of action, we reconstituted wild-type and mutant complexes from recombinant subunits and tested their abilities to assemble chromosomes in Xenopus egg cell-free extracts depleted of endogenous condensins. We find that ATP binding and hydrolysis by SMC subunits have distinct contributions to the action of condensin I and that continuous ATP hydrolysis is required for structural maintenance of chromosomes. Mutant complexes lacking either one of two HEAT subunits produce abnormal chromosomes with highly characteristic defects and have contrasting structural effects on chromosome axes preassembled with the wild-type complex. We propose that balancing acts of the two HEAT subunits support dynamic assembly of chromosome axes under the control of the SMC ATPase cycle, thereby governing construction of rod-shaped chromosomes in eukaryotic cells.", "classifications": [ { "id": "Kobayashi", "label": "Group Kobayashi", "parent": "Wakamoto", "type": "group" }, { "id": "Wakamoto", "label": "Team Wakamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Kazuhisa", "last_name": "Kinoshita", "name": null }, { "creator_type": "author", "first_name": "Tetsuya J.", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Hirano", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.devcel.2015.01.034" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "25850674" } }, "mesh": [ { "descriptor": "Adenosine Triphosphatases", "descriptor_ui": "D000251", "major_topic": false }, { "descriptor": "Adenosine Triphosphate", "descriptor_ui": "D000255", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Binding Sites", "descriptor_ui": "D001665", "major_topic": false }, { "descriptor": "Chromosome Segregation", "descriptor_ui": "D020090", "major_topic": false }, { "descriptor": "Chromosomes", "descriptor_ui": "D002875", "major_topic": false }, { "descriptor": "DNA-Binding Proteins", "descriptor_ui": "D004268", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Fluorescent Antibody Technique", "descriptor_ui": "D005455", "major_topic": false }, { "descriptor": "Immunoprecipitation", "descriptor_ui": "D047468", "major_topic": false }, { "descriptor": "Mitosis", "descriptor_ui": "D008938", "major_topic": false }, { "descriptor": "Multiprotein Complexes", "descriptor_ui": "D046912", "major_topic": false }, { "descriptor": "Nuclear Proteins", "descriptor_ui": "D009687", "major_topic": false }, { "descriptor": "Protein Subunits", "descriptor_ui": "D021122", "major_topic": false }, { "descriptor": "Xenopus laevis", "descriptor_ui": "D014982", "major_topic": false } ], "publication": { "conference_name": null, "date": "2015 Apr 6", "date_precision": "day", "issue": "1", "normalized_date": "2015-04-06", "pages": "94-106", "proceedings_title": null, "publisher": "", "title": "Developmental cell", "volume": "33", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "Balancing acts of two HEAT subunits of condensin I support dynamic assembly of chromosome axes.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "During morphogenesis, three-dimensional (3D) multicellular structures emerge from biochemical and mechanical interplays among cells. In particular, by organizing their gradient within tissues, the diffusible signalling molecules play an essential role in producing the spatio-temporal patterns of cell status such as the differentiation states. Notably, this biochemical patterning can be dynamically coupled with multicellular deformations by signal-dependent cell activities such as contraction, adhesion, migration, proliferation and apoptosis. However, the mechanism by which these cellular activities mediate the interactions between multicellular deformations and patterning is still unknown. Herein, we propose a novel framework of a 3D vertex model to express molecular signalling among the mechanically deforming cells. By specifying a density of signalling molecules for each cell, we express their transport between neighbouring cells. By simulating signal-dependent epithelial growth, we found various types of tissue morphogenesis such as arrest, expansion, invagination and evagination. In the expansion phase, growth molecules were widely diffused with increasing tissue volume, which diluted the growth molecules in order to support the autonomous suppression of tissue growth. These results indicate that the proposed model successfully expresses 3D multicellular deformations dynamically coupled with biochemical patterning. We expect our proposed model to be a useful tool for predicting new phenomena emerging from mechanochemical coupling in multicellular morphogenesis.", "classifications": [ { "id": "Okuda", "label": "Group Okuda", "parent": "Imayoshi", "type": "group" }, { "id": "Imayoshi", "label": "Team Imayoshi", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Satoru", "last_name": "Okuda", "name": null }, { "creator_type": "author", "first_name": "Yasuhiro", "last_name": "Inoue", "name": null }, { "creator_type": "author", "first_name": "Tadashi", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Taiji", "last_name": "Adachi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1098/rsfs.2014.0095" }, "pmcid": { "normalized": "PMC4342952" }, "pmid": { "normalized": "25844156" } }, "mesh": [], "publication": { "conference_name": null, "date": "2015 Apr 6", "date_precision": "day", "issue": "2", "normalized_date": "2015-04-06", "pages": "20140095", "proceedings_title": null, "publisher": "", "title": "Interface focus", "volume": "5", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "Coupling intercellular molecular signalling with multicellular deformation for simulating three-dimensional tissue morphogenesis.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The cystine/glutamate transporter, designated as system xc(-), is important for maintaining intracellular glutathione levels and extracellular redox balance. The substrate-specific component of system xc(-), xCT, is strongly induced by various stimuli, including oxidative stress, whereas it is constitutively expressed only in specific brain regions and immune tissues, such as the thymus and spleen. Although cystine and glutamate are the well established substrates of system xc(-) and the knockout of xCT leads to alterations of extracellular redox balance, nothing is known about other potential substrates. We thus performed a comparative metabolite analysis of tissues from xCT-deficient and wild-type mice using capillary electrophoresis time-of-flight mass spectrometry. Although most of the analyzed metabolites did not show significant alterations between xCT-deficient and wild-type mice, cystathionine emerged as being absent specifically in the thymus and spleen of xCT-deficient mice. No expression of either cystathionine beta-synthase or cystathionine gamma-lyase was observed in the thymus and spleen of mice. In embryonic fibroblasts derived from wild-type embryos, cystine uptake was significantly inhibited by cystathionine in a concentration-dependent manner. Wild-type cells showed an intracellular accumulation of cystathionine when incubated in cystathionine-containing buffer, which concomitantly stimulated an increased release of glutamate into the extracellular space. By contrast, none of these effects could be observed in xCT-deficient cells. Remarkably, unlike knock-out cells, wild-type cells could be rescued from cystine deprivation-induced cell death by cystathionine supplementation. We thus conclude that cystathionine is a novel physiological substrate of system xc(-) and that the accumulation of cystathionine in immune tissues is exclusively mediated by system xc(-).", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Sho", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Mami", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Takayuki", "last_name": "Kasakoshi", "name": null }, { "creator_type": "author", "first_name": "Takumi", "last_name": "Tsutsui", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Sugimoto", "name": null }, { "creator_type": "author", "first_name": "Mitsuhiko", "last_name": "Osaki", "name": null }, { "creator_type": "author", "first_name": "Futoshi", "last_name": "Okada", "name": null }, { "creator_type": "author", "first_name": "Kiharu", "last_name": "Igarashi", "name": null }, { "creator_type": "author", "first_name": "Jun", "last_name": "Hiratake", "name": null }, { "creator_type": "author", "first_name": "Takujiro", "last_name": "Homma", "name": null }, { "creator_type": "author", "first_name": "Marcus", "last_name": "Conrad", "name": null }, { "creator_type": "author", "first_name": "Junichi", "last_name": "Fujii", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Shiro", "last_name": "Bannai", "name": null }, { "creator_type": "author", "first_name": "Hideyo", "last_name": "Sato", "name": null } ], "identifiers": { "doi": { "normalized": "10.1074/jbc.m114.625053" }, "pmcid": { "normalized": "PMC4423669" }, "pmid": { "normalized": "25713140" } }, "mesh": [ { "descriptor": "Amino Acid Transport System y+", "descriptor_ui": "D027182", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Base Sequence", "descriptor_ui": "D001483", "major_topic": false }, { "descriptor": "Cystathionine", "descriptor_ui": "D003540", "major_topic": false }, { "descriptor": "DNA Primers", "descriptor_ui": "D017931", "major_topic": false }, { "descriptor": "Immune System", "descriptor_ui": "D007107", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Reverse Transcriptase Polymerase Chain Reaction", "descriptor_ui": "D020133", "major_topic": false } ], "publication": { "conference_name": null, "date": "2015 Apr 3", "date_precision": "day", "issue": "14", "normalized_date": "2015-04-03", "pages": "8778-8788", "proceedings_title": null, "publisher": "", "title": "The Journal of biological chemistry", "volume": "290", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "Cystathionine is a novel substrate of cystine/glutamate transporter: implications for immune function.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The ERK pathway not only upregulates growth-promoting genes, but also downregulates anti-proliferative and tumor-suppressive genes. In particular, ERK signaling contributes to repression of the E-cadherin gene during epithelial-mesenchymal transition (EMT). The CtBP transcriptional co-repressor is also involved in gene silencing of E-cadherin. However, the functional relationship between ERK signaling and CtBP is unknown. Here, we identified an ERK substrate, designated MCRIP1, which bridges ERK signaling and CtBP-mediated gene silencing. CtBP is recruited to promoter elements of target genes by interacting with the DNA-binding transcriptional repressor ZEB1. We found that MCRIP1 binds to CtBP, thereby competitively inhibiting CtBP-ZEB1 interaction. When phosphorylated by ERK, MCRIP1 dissociates from CtBP, allowing CtBP to interact with ZEB1. In this manner, the CtBP co-repressor complex is recruited to, and silences, the E-cadherin promoter by inducing chromatin modifications. Our findings reveal a molecular mechanism underlying ERK-induced epigenetic gene silencing during EMT and its dysregulation in cancer.", "classifications": [ { "id": "Takekawa", "label": "Group Takekawa", "parent": "Takekawa", "type": "group" }, { "id": "Takekawa", "label": "Team Takekawa", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Kenji", "last_name": "Ichikawa", "name": null }, { "creator_type": "author", "first_name": "Yuji", "last_name": "Kubota", "name": null }, { "creator_type": "author", "first_name": "Takanori", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Jane S.", "last_name": "Weng", "name": null }, { "creator_type": "author", "first_name": "Taichiro", "last_name": "Tomida", "name": null }, { "creator_type": "author", "first_name": "Haruo", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Mutsuhiro", "last_name": "Takekawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.molcel.2015.01.023" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "25728771" } }, "mesh": [ { "descriptor": "Alcohol Oxidoreductases", "descriptor_ui": "D000429", "major_topic": false }, { "descriptor": "Amino Acid Sequence", "descriptor_ui": "D000595", "major_topic": false }, { "descriptor": "Cadherins", "descriptor_ui": "D015820", "major_topic": false }, { "descriptor": "DNA-Binding Proteins", "descriptor_ui": "D004268", "major_topic": false }, { "descriptor": "Epigenesis, Genetic", "descriptor_ui": "D044127", "major_topic": true }, { "descriptor": "Epithelial-Mesenchymal Transition", "descriptor_ui": "D058750", "major_topic": false }, { "descriptor": "Extracellular Signal-Regulated MAP Kinases", "descriptor_ui": "D048049", "major_topic": false }, { "descriptor": "Gene Silencing", "descriptor_ui": "D020868", "major_topic": false }, { "descriptor": "HEK293 Cells", "descriptor_ui": "D057809", "major_topic": false }, { "descriptor": "Homeodomain Proteins", "descriptor_ui": "D018398", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Molecular Sequence Data", "descriptor_ui": "D008969", "major_topic": false }, { "descriptor": "Phosphorylation", "descriptor_ui": "D010766", "major_topic": false }, { "descriptor": "Plasmids", "descriptor_ui": "D010957", "major_topic": false }, { "descriptor": "Promoter Regions, Genetic", "descriptor_ui": "D011401", "major_topic": false }, { "descriptor": "Recombinant Proteins", "descriptor_ui": "D011994", "major_topic": false }, { "descriptor": "Saccharomyces cerevisiae", "descriptor_ui": "D012441", "major_topic": false }, { "descriptor": "Sequence Alignment", "descriptor_ui": "D016415", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Transcription Factors", "descriptor_ui": "D014157", "major_topic": false }, { "descriptor": "Transfection", "descriptor_ui": "D014162", "major_topic": false }, { "descriptor": "Two-Hybrid System Techniques", "descriptor_ui": "D020798", "major_topic": false }, { "descriptor": "Zinc Finger E-box-Binding Homeobox 1", "descriptor_ui": "D000071799", "major_topic": false } ], "publication": { "conference_name": null, "date": "2015 Apr 2", "date_precision": "day", "issue": "1", "normalized_date": "2015-04-02", "pages": "35-46", "proceedings_title": null, "publisher": "", "title": "Molecular cell", "volume": "58", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "MCRIP1, an ERK substrate, mediates ERK-induced gene silencing during epithelial-mesenchymal transition by regulating the co-repressor CtBP.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "MOTIVATION: Recent progress in live-cell imaging and modeling techniques has resulted in generation of a large amount of quantitative data (from experimental measurements and computer simulations) on spatiotemporal dynamics of biological objects such as molecules, cells and organisms. Although many research groups have independently dedicated their efforts to developing software tools for visualizing and analyzing these data, these tools are often not compatible with each other because of different data formats. RESULTS: We developed an open unified format, Biological Dynamics Markup Language (BDML; current version: 0.2), which provides a basic framework for representing quantitative biological dynamics data for objects ranging from molecules to cells to organisms. BDML is based on Extensible Markup Language (XML). Its advantages are machine and human readability and extensibility. BDML will improve the efficiency of development and evaluation of software tools for data visualization and analysis. AVAILABILITY AND IMPLEMENTATION: A specification and a schema file for BDML are freely available online at http://ssbd.qbic.riken.jp/bdml/. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.", "classifications": [ { "id": "Onami", "label": "Group Onami", "parent": "Fujiwara", "type": "group" }, { "id": "Fujiwara", "label": "Team Fujiwara", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Koji", "last_name": "Kyoda", "name": null }, { "creator_type": "author", "first_name": "Yukako", "last_name": "Tohsato", "name": null }, { "creator_type": "author", "first_name": "Kenneth H. L.", "last_name": "Ho", "name": null }, { "creator_type": "author", "first_name": "Shuichi", "last_name": "Onami", "name": null } ], "identifiers": { "doi": { "normalized": "10.1093/bioinformatics/btu767" }, "pmcid": { "normalized": "PMC4382901" }, "pmid": { "normalized": "25414366" } }, "mesh": [ { "descriptor": "Computational Biology", "descriptor_ui": "D019295", "major_topic": false }, { "descriptor": "Computer Graphics", "descriptor_ui": "D003196", "major_topic": true }, { "descriptor": "Computer Simulation", "descriptor_ui": "D003198", "major_topic": false }, { "descriptor": "Databases, Factual", "descriptor_ui": "D016208", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Models, Biological", "descriptor_ui": "D008954", "major_topic": true }, { "descriptor": "Programming Languages", "descriptor_ui": "D011381", "major_topic": true }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Software", "descriptor_ui": "D012984", "major_topic": true }, { "descriptor": "User-Computer Interface", "descriptor_ui": "D014584", "major_topic": false } ], "publication": { "conference_name": null, "date": "2015 Apr 1", "date_precision": "day", "issue": "7", "normalized_date": "2015-04-01", "pages": "1044-1052", "proceedings_title": null, "publisher": "", "title": "Bioinformatics (Oxford, England)", "volume": "31", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "Biological Dynamics Markup Language (BDML): an open format for representing quantitative biological dynamics data.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "A switch of viral hemagglutinin receptor binding specificity from bird-type α2,3- to human-type α2,6-linked sialic acid is necessary for an avian influenza virus to become a pandemic virus. In this study, an easy-to-use strip test to detect receptor binding specificity of influenza virus was developed. A biotinylated anti-hemagglutinin antibody that bound a broad range of group 1 influenza A viruses and latex-conjugated α2,3 (blue) and α2,6 (red) sialylglycopolymers were used in an immunochromatographic strip test, with avidin and lectin immobilized on a nitrocellulose membrane at test and control lines, respectively. Accumulation of a sialylglycopolymer–virus–antibody complex at the test line was visualized by eye. The strip test could be completed in 30 min and did not require special equipment or skills, thereby avoiding some disadvantages of current methods for analyzing receptor binding specificity of influenza virus. The strip test could detect the receptor binding specificity of a wide range of influenza viruses, as well as small increases in the binding affinity of variant H5N1 viruses to α2,6 sialylglycans at viral titers >128 hemagglutination units. The strip test results were in agreement with those of ELISA virus binding assays, with correlations >0.95. In conclusion, the immunochromatographic strip test developed in this study should be useful for monitoring potential changes in the receptor binding specificity of group 1 influenza A viruses in the field.", "classifications": [ { "id": "Suzuki", "label": "Group Suzuki", "parent": "Takekawa", "type": "group" }, { "id": "Takekawa", "label": "Team Takekawa", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yohei", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Tetsuo", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Madiha S.", "last_name": "Ibrahim", "name": null }, { "creator_type": "author", "first_name": "Yasuha", "last_name": "Arai", "name": null }, { "creator_type": "author", "first_name": "Kozue", "last_name": "Hotta", "name": null }, { "creator_type": "author", "first_name": "Hoang Vu Mai", "last_name": "Phuong", "name": null }, { "creator_type": "author", "first_name": "Nguyen Le Khanh", "last_name": "Hang", "name": null }, { "creator_type": "author", "first_name": "Le Quynh", "last_name": "Mai", "name": null }, { "creator_type": "author", "first_name": "Kosuke", "last_name": "Soda", "name": null }, { "creator_type": "author", "first_name": "Masaoki", "last_name": "Yamaoka", "name": null }, { "creator_type": "author", "first_name": "Emmanuel Djoko", "last_name": "Poetranto", "name": null }, { "creator_type": "author", "first_name": "Laksmi", "last_name": "Wulandari", "name": null }, { "creator_type": "author", "first_name": "Hiroaki", "last_name": "Hiramatsu", "name": null }, { "creator_type": "author", "first_name": "Tomo", "last_name": "Daidoji", "name": null }, { "creator_type": "author", "first_name": "Ritsuko", "last_name": "Kubota-Koketsu", "name": null }, { "creator_type": "author", "first_name": "Nongluk", "last_name": "Sriwilaijaroen", "name": null }, { "creator_type": "author", "first_name": "Takaaki", "last_name": "Nakaya", "name": null }, { "creator_type": "author", "first_name": "Yoshinobu", "last_name": "Okuno", "name": null }, { "creator_type": "author", "first_name": "Tadanobu", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Toshihiro", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Hak", "last_name": "Hotta", "name": null }, { "creator_type": "author", "first_name": "Tetsu", "last_name": "Yamashiro", "name": null }, { "creator_type": "author", "first_name": "Tsukasa", "last_name": "Hayashi", "name": null }, { "creator_type": "author", "first_name": "Kouichi", "last_name": "Morita", "name": null }, { "creator_type": "author", "first_name": "Kazuyoshi", "last_name": "Ikuta", "name": null }, { "creator_type": "author", "first_name": "Yasuo", "last_name": "Suzuki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.bios.2014.10.036" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "25461160" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Birds", "descriptor_ui": "D001717", "major_topic": false }, { "descriptor": "Chromatography, Affinity", "descriptor_ui": "D002846", "major_topic": false }, { "descriptor": "Equipment Design", "descriptor_ui": "D004867", "major_topic": false }, { "descriptor": "Hemagglutinin Glycoproteins, Influenza Virus", "descriptor_ui": "D019267", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Influenza A virus", "descriptor_ui": "D009980", "major_topic": false }, { "descriptor": "Influenza A Virus, H5N1 Subtype", "descriptor_ui": "D053124", "major_topic": false }, { "descriptor": "Influenza in Birds", "descriptor_ui": "D005585", "major_topic": false }, { "descriptor": "Influenza, Human", "descriptor_ui": "D007251", "major_topic": false }, { "descriptor": "Reagent Strips", "descriptor_ui": "D011934", "major_topic": false } ], "publication": { "conference_name": null, "date": "2015 Mar 15", "date_precision": "day", "issue": "", "normalized_date": "2015-03-15", "pages": "211-219", "proceedings_title": null, "publisher": "", "title": "Biosensors & Bioelectronics", "volume": "65", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "A novel immunochromatographic system for easy-to-use detection of group 1 avian influenza viruses with acquired human-type receptor binding specificity.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Cytokines, including interleukin-6 (IL-6), play an important role in the liver. The aim of this study was to investigate associations between common polymorphisms in potential functional promoters of cytokine genes and liver damage markers among enrollees of a large Japanese cohort study. Subjects included 3257 Japanese individuals (1608 men and 1649 women, aged 35-69 years). Six single nucleotide polymorphisms (SNPs) in the promoter regions of five cytokine genes, IL1B (T-31C), IL6 (C-634G), IL8 (T-251A), IL10 (T-819C), tumor necrosis factor-A (TNFA) (T-1031C), and TNFA (C-857T), were genotyped by polymerase chain reaction. Information regarding alcohol intake, smoking habits, height, and weight was collected by a self-administered questionnaire. Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were measured during a routine health check-up. Of the six SNPs genotyped, an IL6 polymorphism (rs1800796, C-634G) was most strongly associated with a liver damage marker, AST. Mean serum AST was significantly different among the three genotypes (mean +/- SD, 22.7 +/- 7.3 IU/L for CC, 22.8 +/- 7.7 IU/L for CG, and 24.3 +/- 8.6 IU/L for GG, p=0.011 by analysis of variance). The differences remained significant after adjustment for potential confounders by general linear models. The variations in mean serum AST and ALT levels were marked especially among men. Thus, the functional polymorphism IL6 C-634G may affect serum AST and ALT levels, possibly through different IL-6 production.", "classifications": [ { "id": "Tanaka", "label": "Group Tanaka", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yuka", "last_name": "Sugimoto", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Wakai", "name": null }, { "creator_type": "author", "first_name": "Hiroko", "last_name": "Nakagawa", "name": null }, { "creator_type": "author", "first_name": "Shino", "last_name": "Suma", "name": null }, { "creator_type": "author", "first_name": "Tae", "last_name": "Sasakabe", "name": null }, { "creator_type": "author", "first_name": "Tatsuhiko", "last_name": "Sakamoto", "name": null }, { "creator_type": "author", "first_name": "Naoyuki", "last_name": "Takashima", "name": null }, { "creator_type": "author", "first_name": "Sadao", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Shin", "last_name": "Ogawa", "name": null }, { "creator_type": "author", "first_name": "Keizo", "last_name": "Ohnaka", "name": null }, { "creator_type": "author", "first_name": "Nagato", "last_name": "Kuriyama", "name": null }, { "creator_type": "author", "first_name": "Kokichi", "last_name": "Arisawa", "name": null }, { "creator_type": "author", "first_name": "Haruo", "last_name": "Mikami", "name": null }, { "creator_type": "author", "first_name": "Michiaki", "last_name": "Kubo", "name": null }, { "creator_type": "author", "first_name": "Satoyo", "last_name": "Hosono", "name": null }, { "creator_type": "author", "first_name": "Nobuyuki", "last_name": "Hamajima", "name": null }, { "creator_type": "author", "first_name": "Hideo", "last_name": "Tanaka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.gene.2014.12.025" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "25523094" } }, "mesh": [ { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Alanine Transaminase", "descriptor_ui": "D000410", "major_topic": false }, { "descriptor": "Aspartate Aminotransferases", "descriptor_ui": "D001219", "major_topic": false }, { "descriptor": "Biomarkers", "descriptor_ui": "D015415", "major_topic": false }, { "descriptor": "Cross-Sectional Studies", "descriptor_ui": "D003430", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Genetic Association Studies", "descriptor_ui": "D056726", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Interleukin-6", "descriptor_ui": "D015850", "major_topic": false }, { "descriptor": "Japan", "descriptor_ui": "D007564", "major_topic": false }, { "descriptor": "Liver Diseases", "descriptor_ui": "D008107", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Polymorphism, Single Nucleotide", "descriptor_ui": "D020641", "major_topic": false }, { "descriptor": "Promoter Regions, Genetic", "descriptor_ui": "D011401", "major_topic": false } ], "publication": { "conference_name": null, "date": "2015 Feb 25", "date_precision": "day", "issue": "2", "normalized_date": "2015-02-25", "pages": "158-162", "proceedings_title": null, "publisher": "", "title": "Gene", "volume": "557", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "Associations between polymorphisms of interleukin-6 and related cytokine genes and serum liver damage markers: a cross-sectional study in the Japan Multi-Institutional Collaborative Cohort (J-MICC) Study.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The precise pathways of memory T-cell differentiation are incompletely understood. Here we exploit transgenic mice expressing fluorescent cell cycle indicators to longitudinally track the division dynamics of individual CD8(+) T cells. During influenza virus infection in vivo, naive T cells enter a CD62L(intermediate) state of fast proliferation, which continues for at least nine generations. At the peak of the anti-viral immune response, a subpopulation of these cells markedly reduces their cycling speed and acquires a CD62L(hi) central memory cell phenotype. Construction of T-cell family division trees in vitro reveals two patterns of proliferation dynamics. While cells initially divide rapidly with moderate stochastic variations of cycling times after each generation, a slow-cycling subpopulation displaying a CD62L(hi) memory phenotype appears after eight divisions. Phenotype and cell cycle duration are inherited by the progeny of slow cyclers. We propose that memory precursors cell-intrinsically modulate their proliferative activity to diversify differentiation pathways.", "classifications": [ { "id": "Sawano", "label": "Group Sawano", "parent": "Shintaku", "type": "group" }, { "id": "Shintaku", "label": "Team Shintaku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Ichiko", "last_name": "Kinjyo", "name": null }, { "creator_type": "author", "first_name": "Jim", "last_name": "Qin", "name": null }, { "creator_type": "author", "first_name": "Sioh-Yang", "last_name": "Tan", "name": null }, { "creator_type": "author", "first_name": "Cameron J.", "last_name": "Wellard", "name": null }, { "creator_type": "author", "first_name": "Paulus", "last_name": "Mrass", "name": null }, { "creator_type": "author", "first_name": "William", "last_name": "Ritchie", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Doi", "name": null }, { "creator_type": "author", "first_name": "Lois L.", "last_name": "Cavanagh", "name": null }, { "creator_type": "author", "first_name": "Michio", "last_name": "Tomura", "name": null }, { "creator_type": "author", "first_name": "Asako", "last_name": "Sakaue-Sawano", "name": null }, { "creator_type": "author", "first_name": "Osami", "last_name": "Kanagawa", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Miyawaki", "name": null }, { "creator_type": "author", "first_name": "Philip D.", "last_name": "Hodgkin", "name": null }, { "creator_type": "author", "first_name": "Wolfgang", "last_name": "Weninger", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/ncomms7301" }, "pmcid": { "normalized": "PMC4346633" }, "pmid": { "normalized": "25709008" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "CD8-Positive T-Lymphocytes", "descriptor_ui": "D018414", "major_topic": false }, { "descriptor": "Cell Cycle", "descriptor_ui": "D002453", "major_topic": true }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": true }, { "descriptor": "Gene Expression Profiling", "descriptor_ui": "D020869", "major_topic": false }, { "descriptor": "Genes, Reporter", "descriptor_ui": "D017930", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Transgenic", "descriptor_ui": "D008822", "major_topic": false }, { "descriptor": "Transcriptome", "descriptor_ui": "D059467", "major_topic": false } ], "publication": { "conference_name": null, "date": "2015 Feb 24", "date_precision": "day", "issue": "", "normalized_date": "2015-02-24", "pages": "6301", "proceedings_title": null, "publisher": "", "title": "Nature communications", "volume": "6", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "Real-time tracking of cell cycle progression during CD8+ effector and memory T-cell differentiation.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "In biological cells, chemical reaction pathways lead to complex network systems like metabolic networks. One experimental approach to the dynamics of such systems examines their \"sensitivity\": each enzyme mediating a reaction in the system is increased/decreased or knocked out separately, and the responses in the concentrations of chemicals or their fluxes are observed. In this study, we present a mathematical method, named structural sensitivity analysis, to determine the sensitivity of reaction systems from information on the network alone. We investigate how the sensitivity responses of chemicals in a reaction network depend on the structure of the network, and on the position of the perturbed reaction in the network. We establish and prove some general rules which relate the sensitivity response to the structure of the underlying network. We describe a hierarchical pattern in the flux response which is governed by branchings in the network. We apply our method to several hypothetical and real life chemical reaction networks, including the metabolic network of the Escherichia coli TCA cycle.", "classifications": [ { "id": "Mochizuki", "label": "Group Mochizuki", "parent": "Eiraku", "type": "group" }, { "id": "Eiraku", "label": "Team Eiraku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Atsushi", "last_name": "Mochizuki", "name": null }, { "creator_type": "author", "first_name": "Bernold", "last_name": "Fiedler", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.jtbi.2014.10.025" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "25451520" } }, "mesh": [ { "descriptor": "Carbon", "descriptor_ui": "D002244", "major_topic": false }, { "descriptor": "Chemical Phenomena", "descriptor_ui": "D055598", "major_topic": true }, { "descriptor": "Citric Acid Cycle", "descriptor_ui": "D002952", "major_topic": false }, { "descriptor": "Escherichia coli", "descriptor_ui": "D004926", "major_topic": false }, { "descriptor": "Feedback, Physiological", "descriptor_ui": "D025461", "major_topic": false }, { "descriptor": "Metabolic Networks and Pathways", "descriptor_ui": "D053858", "major_topic": true } ], "publication": { "conference_name": null, "date": "2015 Feb 21", "date_precision": "day", "issue": "", "normalized_date": "2015-02-21", "pages": "189-202", "proceedings_title": null, "publisher": "", "title": "Journal of theoretical biology", "volume": "367", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "Sensitivity of chemical reaction networks: a structural approach. 1. Examples and the carbon metabolic network.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Intracellular redox state is a critical factor for fundamental cellular functions, including regulation of the activities of various metabolic enzymes as well as ROS production and elimination. Genetically-encoded fluorescent redox sensors, such as roGFP (Hanson, G. T., et al. (2004)) and Redoxfluor (Yano, T., et al. (2010)), have been developed to investigate the redox state of living cells. However, these sensors are not useful in cells that contain, for example, other colored pigments. We therefore intended to obtain simpler redox sensor proteins, and have developed oxidation-sensitive fluorescent proteins called Oba-Q (oxidation balance sensed quenching) proteins. Our sensor proteins derived from CFP and Sirius can be used to monitor the intracellular redox state as their fluorescence is drastically quenched upon oxidation. These blue-shifted spectra of the Oba-Q proteins enable us to monitor various redox states in conjunction with other sensor proteins.", "classifications": [ { "id": "Nakabayashi", "label": "Group Nakabayashi", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Kazunori", "last_name": "Sugiura", "name": null }, { "creator_type": "author", "first_name": "Takeharu", "last_name": "Nagai", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Nakano", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Ichinose", "name": null }, { "creator_type": "author", "first_name": "Takakazu", "last_name": "Nakabayashi", "name": null }, { "creator_type": "author", "first_name": "Nobuhiro", "last_name": "Ohta", "name": null }, { "creator_type": "author", "first_name": "Toru", "last_name": "Hisabori", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.bbrc.2014.12.095" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "25592971" } }, "mesh": [ { "descriptor": "Biosensing Techniques", "descriptor_ui": "D015374", "major_topic": false }, { "descriptor": "Glutathione", "descriptor_ui": "D005978", "major_topic": false }, { "descriptor": "Glutathione Disulfide", "descriptor_ui": "D019803", "major_topic": false }, { "descriptor": "Green Fluorescent Proteins", "descriptor_ui": "D049452", "major_topic": false }, { "descriptor": "HeLa Cells", "descriptor_ui": "D006367", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Intracellular Fluid", "descriptor_ui": "D007424", "major_topic": false }, { "descriptor": "Mutagenesis", "descriptor_ui": "D016296", "major_topic": false }, { "descriptor": "Oxidation-Reduction", "descriptor_ui": "D010084", "major_topic": false }, { "descriptor": "Quantum Theory", "descriptor_ui": "D011789", "major_topic": false }, { "descriptor": "Recombinant Fusion Proteins", "descriptor_ui": "D011993", "major_topic": false }, { "descriptor": "Spectrometry, Fluorescence", "descriptor_ui": "D013050", "major_topic": false } ], "publication": { "conference_name": null, "date": "2015 Feb 13", "date_precision": "day", "issue": "3", "normalized_date": "2015-02-13", "pages": "242-248", "proceedings_title": null, "publisher": "", "title": "Biochemical and biophysical research communications", "volume": "457", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "Redox sensor proteins for highly sensitive direct imaging of intracellular redox state.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The biochemistry of cancer cells diverges significantly from normal cells as a result of a comprehensive reprogramming of metabolic pathways. A major factor influencing cancer metabolism is hypoxia, which is mediated by HIF1alpha and HIF2alpha. HIF1alpha represents one of the principal regulators of metabolism and energetic balance in cancer cells through its regulation of glycolysis, glycogen synthesis, Krebs cycle and the pentose phosphate shunt. However, less is known about the role of HIF1alpha in modulating lipid metabolism. Lipids serve cancer cells to provide molecules acting as oncogenic signals, energetic reserve, precursors for new membrane synthesis and to balance redox biological reactions. To study the role of HIF1alpha in these processes, we used HCT116 colorectal cancer cells expressing endogenous HIF1alpha and cells in which the hif1alpha gene was deleted to characterize HIF1alpha-dependent and independent effects on hypoxia regulated lipid metabolites. Untargeted metabolomics integrated with proteomics revealed that hypoxia induced many changes in lipids metabolites. Enzymatic steps in fatty acid synthesis and the Kennedy pathway were modified in a HIF1alpha-dependent fashion. Palmitate, stearate, PLD3 and PAFC16 were regulated in a HIF-independent manner. Our results demonstrate the impact of hypoxia on lipid metabolites, of which a distinct subset is regulated by HIF1alpha.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Alessandro", "last_name": "Valli", "name": null }, { "creator_type": "author", "first_name": "Miguel", "last_name": "Rodriguez", "name": null }, { "creator_type": "author", "first_name": "Loukas", "last_name": "Moutsianas", "name": null }, { "creator_type": "author", "first_name": "Roman", "last_name": "Fischer", "name": null }, { "creator_type": "author", "first_name": "Vita", "last_name": "Fedele", "name": null }, { "creator_type": "author", "first_name": "Hong-Lei", "last_name": "Huang", "name": null }, { "creator_type": "author", "first_name": "Ruud", "last_name": "Van Stiphout", "name": null }, { "creator_type": "author", "first_name": "Dylan", "last_name": "Jones", "name": null }, { "creator_type": "author", "first_name": "Michael", "last_name": "Mccarthy", "name": null }, { "creator_type": "author", "first_name": "Maria", "last_name": "Vinaxia", "name": null }, { "creator_type": "author", "first_name": "Kaori", "last_name": "Igarashi", "name": null }, { "creator_type": "author", "first_name": "Maya", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Francesca", "last_name": "Buffa", "name": null }, { "creator_type": "author", "first_name": "James", "last_name": "Mccullagh", "name": null }, { "creator_type": "author", "first_name": "Oscar", "last_name": "Yanes", "name": null }, { "creator_type": "author", "first_name": "Adrian", "last_name": "Harris", "name": null }, { "creator_type": "author", "first_name": "Benedikt", "last_name": "Kessler", "name": null } ], "identifiers": { "doi": { "normalized": "10.18632/oncotarget.3058" }, "pmcid": { "normalized": "PMC4385826" }, "pmid": { "normalized": "25605240" } }, "mesh": [ { "descriptor": "Acetyl-CoA C-Acyltransferase", "descriptor_ui": "D000102", "major_topic": false }, { "descriptor": "Acetyl-CoA Carboxylase", "descriptor_ui": "D000103", "major_topic": false }, { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Basic Helix-Loop-Helix Proteins", "descriptor_ui": "D051792", "major_topic": false }, { "descriptor": "Blotting, Western", "descriptor_ui": "D015153", "major_topic": false }, { "descriptor": "Cell Hypoxia", "descriptor_ui": "D015687", "major_topic": false }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Colorectal Neoplasms", "descriptor_ui": "D015179", "major_topic": false }, { "descriptor": "Endothelial PAS Domain-Containing Protein 1", "descriptor_ui": "D000099162", "major_topic": false }, { "descriptor": "Fatty Acids", "descriptor_ui": "D005227", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Genomics", "descriptor_ui": "D023281", "major_topic": false }, { "descriptor": "HCT116 Cells", "descriptor_ui": "D045325", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Hypoxia-Inducible Factor 1, alpha Subunit", "descriptor_ui": "D051795", "major_topic": false }, { "descriptor": "Lipid Metabolism", "descriptor_ui": "D050356", "major_topic": true }, { "descriptor": "Lipids", "descriptor_ui": "D008055", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Metabolomics", "descriptor_ui": "D055432", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Platelet Activating Factor", "descriptor_ui": "D010972", "major_topic": false }, { "descriptor": "Proteomics", "descriptor_ui": "D040901", "major_topic": false }, { "descriptor": "RNA Interference", "descriptor_ui": "D034622", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": true } ], "publication": { "conference_name": null, "date": "2015 Feb 10", "date_precision": "day", "issue": "4", "normalized_date": "2015-02-10", "pages": "1920-1941", "proceedings_title": null, "publisher": "", "title": "Oncotarget", "volume": "6", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "Hypoxia induces a lipogenic cancer cell phenotype via HIF1alpha-dependent and -independent pathways.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "We previously showed that bisarylbutadiyne (BADY), which has a conjugated diyne structure, exhibits an intense peak in the cellular Raman-silent region. Here, we synthesized a mitochondria-selective Raman probe by linking bisphenylbutadiyne with triphenylphosphonium, a well-known mitochondrial targeting moiety. This probe, named MitoBADY, has a Raman peak 27 times more intense than that of 5-ethynyl-2'-deoxyuridine. Raman microscopy using submicromolar extracellular probe concentrations successfully visualized mitochondria in living cells. A full Raman spectrum is acquired at each pixel of the scanned sample, and we showed that simultaneous Raman imaging of MitoBADY and endogenous cellular biomolecules can be achieved in a single scan. MitoBADY should be useful for the study of mitochondrial dynamics.", "classifications": [ { "id": "Fujita", "label": "Group Fujita", "parent": "Fujita", "type": "group" }, { "id": "Sodeoka", "label": "Group Sodeoka", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Yamakoshi", "name": null }, { "creator_type": "author", "first_name": "Almar", "last_name": "Palonpon", "name": null }, { "creator_type": "author", "first_name": "Kosuke", "last_name": "Dodo", "name": null }, { "creator_type": "author", "first_name": "Jun", "last_name": "Ando", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Kawata", "name": null }, { "creator_type": "author", "first_name": "Katsumasa", "last_name": "Fujita", "name": null }, { "creator_type": "author", "first_name": "Mikiko", "last_name": "Sodeoka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.bmcl.2014.11.080" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "25522818" } }, "mesh": [ { "descriptor": "Alkynes", "descriptor_ui": "D000480", "major_topic": false }, { "descriptor": "Deoxyuridine", "descriptor_ui": "D003857", "major_topic": false }, { "descriptor": "HeLa Cells", "descriptor_ui": "D006367", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Microscopy, Fluorescence", "descriptor_ui": "D008856", "major_topic": false }, { "descriptor": "Mitochondria", "descriptor_ui": "D008928", "major_topic": false }, { "descriptor": "Spectrum Analysis, Raman", "descriptor_ui": "D013059", "major_topic": true } ], "publication": { "conference_name": null, "date": "2015 Feb 1", "date_precision": "day", "issue": "3", "normalized_date": "2015-02-01", "pages": "664-667", "proceedings_title": null, "publisher": "", "title": "Bioorganic & medicinal chemistry letters", "volume": "25", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "A sensitive and specific Raman probe based on bisarylbutadiyne for live cell imaging of mitochondria.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Fluorescent ubiquitination-based cell cycle indicator (Fucci) technology utilizing the cell cycle-dependent proteolysis of ubiquitin oscillators enables visualization of cell cycle progression in living cells. The Fucci probe consists of two chimeric fluorescent proteins, FucciS/G2/M and FucciG1, which label the nuclei of cells in S/G2/M phase green and those in G1 phase red, respectively. In this study, we generated Fucci transgenic mice and analyzed transgene expression in hematopoietic cells using flow cytometry. The FucciS/G2/M-#474 and FucciG1-#639 mouse lines exhibited high-level transgene expression in most hematopoietic cell populations. The FucciG1-#610 line expressed the transgene at high levels predominantly in the hematopoietic stem cell (HSC) population. Analysis of the HSC (CD34(-)KSL: CD34(-/low)c-Kit(+)Sca-1(+)lineage marker(-)) population in the transgenic mice expressing both FucciS/G2/M and FucciG1 (#474/#610) confirmed that more than 95% of the cells were in G0/G1 phase, although the FucciG1(red) intensity was heterogeneous. An in vivo competitive repopulation assay revealed that repopulating activity resided largely in the FucciG1(red)(high) fraction of CD34(-)KSL cells. Thus, the CD34(-)KSL HSC population can be further purified on the basis of the Fucci intensity.", "classifications": [ { "id": "Sawano", "label": "Group Sawano", "parent": "Shintaku", "type": "group" }, { "id": "Shintaku", "label": "Team Shintaku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Masahiro", "last_name": "Yo", "name": null }, { "creator_type": "author", "first_name": "Asako", "last_name": "Sakaue-Sawano", "name": null }, { "creator_type": "author", "first_name": "Shinichi", "last_name": "Noda", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Miyawaki", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Miyoshi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.bbrc.2014.12.074" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "25534850" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Cycle", "descriptor_ui": "D002453", "major_topic": true }, { "descriptor": "Cell Separation", "descriptor_ui": "D002469", "major_topic": false }, { "descriptor": "Flow Cytometry", "descriptor_ui": "D005434", "major_topic": false }, { "descriptor": "Fluorescence", "descriptor_ui": "D005453", "major_topic": false }, { "descriptor": "Fluorescent Dyes", "descriptor_ui": "D005456", "major_topic": false }, { "descriptor": "Hematopoietic Stem Cells", "descriptor_ui": "D006412", "major_topic": false }, { "descriptor": "Mice, Transgenic", "descriptor_ui": "D008822", "major_topic": false }, { "descriptor": "Transgenes", "descriptor_ui": "D019076", "major_topic": false }, { "descriptor": "Ubiquitination", "descriptor_ui": "D054875", "major_topic": true } ], "publication": { "conference_name": null, "date": "2015 Jan 30", "date_precision": "day", "issue": "1", "normalized_date": "2015-01-30", "pages": "7-11", "proceedings_title": null, "publisher": "", "title": "Biochemical and biophysical research communications", "volume": "457", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "Fucci-guided purification of hematopoietic stem cells with high repopulating activity.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Inhomogeneous distribution of auxin is essential in various differentiation processes of plant development. Auxin transfer between cells by efflux carrier protein called PINFORMED (PIN) has been considered to be responsible for inhomogeneous distribution of auxin. Two major types of auxin distribution patterns are \"spot\" patterns and \"passage\" patterns, which are responsible for determining the position of the primordia of a leaf or flower in shoot apical meristem and formation of leaf veins, respectively. In this study, we studied the pattern formation of auxin distribution mediated by polarization of PIN using mathematical methods. We developed several different models which show possible interaction mechanisms between auxin and PIN on 2-dimentional hexagonal cellular lattice, (1) Basic auxin flux model, (2) auxin-dependent PIN degradation model and (3) auxin self-feedback model. We analyzed these models by numerical calculation and mathematical analysis. From intensive numerical calculations under different conditions, we found that some models show three different types of pattern formations in dynamics, (a) homogeneous, (b) passage and (c) spot pattern depending on parameter condition. We analyzed these models mathematically using approximation of 1-dimensional periodic space. We determined the conditions that passage and spot patterns are generated in each model, respectively. After these analyses, we propose possible mechanisms by which plants switch passage and spot patterns in different organs by small modification.", "classifications": [ { "id": "Mochizuki", "label": "Group Mochizuki", "parent": "Eiraku", "type": "group" }, { "id": "Eiraku", "label": "Team Eiraku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yoshinori", "last_name": "Hayakawa", "name": null }, { "creator_type": "author", "first_name": "Masashi", "last_name": "Tachikawa", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Mochizuki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.jtbi.2014.09.039" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "25303888" } }, "mesh": [ { "descriptor": "Biological Transport", "descriptor_ui": "D001692", "major_topic": false }, { "descriptor": "Carrier Proteins", "descriptor_ui": "D002352", "major_topic": false }, { "descriptor": "Indoleacetic Acids", "descriptor_ui": "D007210", "major_topic": false }, { "descriptor": "Models, Biological", "descriptor_ui": "D008954", "major_topic": true }, { "descriptor": "Plant Development", "descriptor_ui": "D063245", "major_topic": false }, { "descriptor": "Plant Proteins", "descriptor_ui": "D010940", "major_topic": false } ], "publication": { "conference_name": null, "date": "2015 Jan 21", "date_precision": "day", "issue": "", "normalized_date": "2015-01-21", "pages": "12-22", "proceedings_title": null, "publisher": "", "title": "Journal of theoretical biology", "volume": "365", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "Mathematical study for the mechanism of vascular and spot patterns by auxin and pin dynamics in plant development.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The design of inexpensive and less toxic porous coordination polymers (PCPs) that show selective adsorption or high adsorption capacity is a critical issue in research on applicable porous materials. Although use of Group II magnesium(II) and calcium(II) ions as building blocks could provide cheaper materials and lead to enhanced biocompatibility, examples of magnesium(II) and calcium(II) PCPs are extremely limited compared with commonly used transition metal ones, because neutral bridging ligands have not been available for magnesium(II) and calcium(II) ions. Here we report a rationally designed neutral and charge-polarized bridging ligand as a new partner for magnesium(II) and calcium(II) ions. The three-dimensional magnesium(II) and calcium(II) PCPs synthesized using such a neutral ligand are stable and show selective adsorption and separation of carbon dioxide over methane at ambient temperature. This synthetic approach allows the structural diversification of Group II magnesium(II) and calcium(II) PCPs.", "classifications": [ { "id": "Hijikata", "label": "Group Hijikata", "parent": "Tsuchiya", "type": "group" }, { "id": "Tsuchiya", "label": "Team Tsuchiya", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Shin-ichiro", "last_name": "Noro", "name": null }, { "creator_type": "author", "first_name": "Junya", "last_name": "Mizutani", "name": null }, { "creator_type": "author", "first_name": "Yuh", "last_name": "Hijikata", "name": null }, { "creator_type": "author", "first_name": "Ryotaro", "last_name": "Matsuda", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Susumu", "last_name": "Kitagawa", "name": null }, { "creator_type": "author", "first_name": "Kunihisa", "last_name": "Sugimoto", "name": null }, { "creator_type": "author", "first_name": "Yasutaka", "last_name": "Inubushi", "name": null }, { "creator_type": "author", "first_name": "Kazuya", "last_name": "Kubo", "name": null }, { "creator_type": "author", "first_name": "Takayoshi", "last_name": "Nakamura", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/ncomms6851" }, "pmcid": { "normalized": "PMC4309420" }, "pmid": { "normalized": "25592677" } }, "mesh": [ { "descriptor": "Adsorption", "descriptor_ui": "D000327", "major_topic": false }, { "descriptor": "Biocompatible Materials", "descriptor_ui": "D001672", "major_topic": false }, { "descriptor": "Calcium", "descriptor_ui": "D002118", "major_topic": false }, { "descriptor": "Magnesium", "descriptor_ui": "D008274", "major_topic": false }, { "descriptor": "Metals", "descriptor_ui": "D008670", "major_topic": false }, { "descriptor": "Molecular Structure", "descriptor_ui": "D015394", "major_topic": false }, { "descriptor": "Polymers", "descriptor_ui": "D011108", "major_topic": false }, { "descriptor": "Porosity", "descriptor_ui": "D016062", "major_topic": false } ], "publication": { "conference_name": null, "date": "2015 Jan 16", "date_precision": "day", "issue": "", "normalized_date": "2015-01-16", "pages": "5851", "proceedings_title": null, "publisher": "", "title": "Nature communications", "volume": "6", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "Porous coordination polymers with ubiquitous and biocompatible metals and a neutral bridging ligand.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The cytoplasms of ameboid cells are nonlinearly viscous. The cell controls this viscosity by modulating the amount, localization and interactions of bio-polymers. Here we investigated how the nonlinearity infers the cellular behaviors and whether nonlinearity-specific behaviors exist. We modeled the developed plasmodium of the slime mold Physarum polycephalum as a network of branching tubes and examined the linear and nonlinear viscous cytoplasm flows in the tubes. We found that the nonlinearity in the cytoplasm׳s viscosity induces a novel type of symmetry breaking in the protoplasmic flow. We also show that symmetry breaking can play an important role in adaptive behaviors, namely, connection of behavioral modes implemented on different time scales and transportation of molecular signals from the front to the rear of the cell during cellular locomotion.", "classifications": [ { "id": "Mochizuki", "label": "Group Mochizuki", "parent": "Eiraku", "type": "group" }, { "id": "Eiraku", "label": "Team Eiraku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Masashi", "last_name": "Tachikawa", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Mochizuki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.jtbi.2014.09.023" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "25261729" } }, "mesh": [ { "descriptor": "Cytoplasm", "descriptor_ui": "D003593", "major_topic": false }, { "descriptor": "Cytosol", "descriptor_ui": "D003600", "major_topic": false }, { "descriptor": "Locomotion", "descriptor_ui": "D008124", "major_topic": true }, { "descriptor": "Models, Biological", "descriptor_ui": "D008954", "major_topic": false }, { "descriptor": "Physarum polycephalum", "descriptor_ui": "D016839", "major_topic": false }, { "descriptor": "Polymers", "descriptor_ui": "D011108", "major_topic": false }, { "descriptor": "Pressure", "descriptor_ui": "D011312", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Viscosity", "descriptor_ui": "D014783", "major_topic": false } ], "publication": { "conference_name": null, "date": "2015 Jan 7", "date_precision": "day", "issue": "", "normalized_date": "2015-01-07", "pages": "260-265", "proceedings_title": null, "publisher": "", "title": "Journal of theoretical biology", "volume": "364", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "Nonlinearity in cytoplasm viscosity can generate an essential symmetry breaking in cellular behaviors.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The selective synthesis of multiarylated acetonitriles via sequential palladium-catalyzed arylations of chloroacetonitrile is reported. The three aryl groups are installed via a Pd-catalyzed Suzuki-Miyaura cross coupling reaction followed by back-to-back C-H arylations to afford triarylacetonitriles in three steps with no over-arylation at any step. The triarylacetonitrile products can be converted into highly functionalized species including tetraarylmethanes. This new strategy provides rapid access to a variety of unsymmetrical tri- and tetraarylmethane derivatives from simple, readily available starting materials.", "classifications": [ { "id": "Nanbo", "label": "Group Nanbo", "parent": "Tsuchiya", "type": "group" }, { "id": "Tsuchiya", "label": "Team Tsuchiya", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Masakazu", "last_name": "Nambo", "name": null }, { "creator_type": "author", "first_name": "Muhammad", "last_name": "Yar", "name": null }, { "creator_type": "author", "first_name": "Joel D.", "last_name": "Smith", "name": null }, { "creator_type": "author", "first_name": "Cathleen M.", "last_name": "Crudden", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/ol503213z" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "25523024" } }, "mesh": [ { "descriptor": "Catalysis", "descriptor_ui": "D002384", "major_topic": false }, { "descriptor": "Combinatorial Chemistry Techniques", "descriptor_ui": "D020650", "major_topic": false }, { "descriptor": "Methane", "descriptor_ui": "D008697", "major_topic": false }, { "descriptor": "Molecular Structure", "descriptor_ui": "D015394", "major_topic": false }, { "descriptor": "Nitriles", "descriptor_ui": "D009570", "major_topic": false }, { "descriptor": "Palladium", "descriptor_ui": "D010165", "major_topic": false } ], "publication": { "conference_name": null, "date": "2015 Jan 2", "date_precision": "day", "issue": "1", "normalized_date": "2015-01-02", "pages": "50-53", "proceedings_title": null, "publisher": "", "title": "Organic letters", "volume": "17", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "The concise synthesis of unsymmetric triarylacetonitriles via Pd-catalyzed sequential arylation: a new synthetic approach to tri- and tetraarylmethanes.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Interaction only within specific molecules is a requisite for accurate operations of a biochemical reaction in a cell where bulk of background molecules exist. While structural specificity is a well-established mechanism for specific interaction, biophysical and biochemical experiments indicate that the mechanism is not sufficient for accounting for the antigen discrimination by T cells. In addition, the antigen discrimination by T cells also accompanies three intriguing properties other than the specificity: sensitivity, speed, and concentration compensation. In this work, we review experimental and theoretical works on the antigen discrimination by focusing on these four properties and show future directions towards understanding of the fundamental principle for molecular discrimination.", "classifications": [ { "id": "Kobayashi", "label": "Group Kobayashi", "parent": "Wakamoto", "type": "group" }, { "id": "Wakamoto", "label": "Team Wakamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Masashi K.", "last_name": "Kajita", "name": null }, { "creator_type": "author", "first_name": "Ryo", "last_name": "Yokota", "name": null }, { "creator_type": "author", "first_name": "Kazuyuki", "last_name": "Aihara", "name": null }, { "creator_type": "author", "first_name": "Tetsuya J.", "last_name": "Kobayashi", "name": null } ], "identifiers": { "doi": { "normalized": "10.2142/biophysics.11.85" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "27493520" } }, "mesh": [], "publication": { "conference_name": null, "date": "2015", "date_precision": "year", "issue": "", "normalized_date": "2015", "pages": "85-92", "proceedings_title": null, "publisher": "", "title": "Biophysics", "volume": "11", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "Experimental and theoretical bases for mechanisms of antigen discrimination by T cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Breast cancer is the most common type of cancer in women. The 5-year survival rate in patients with breast cancer ranges from 74 to 82 %. Sentinel lymph node biopsy has become an alternative to axillary lymph node dissection for nodal staging. We evaluated the detection of the sentinel lymph node and metastasis of the lymph node using contrast enhanced ultrasonography with Sonazoid. Between December 2013 and May 2014, 32 patients with operable breast cancer were enrolled in this study. We evaluated the detection of axillary sentinel lymph nodes and the evaluation of axillary lymph nodes metastasis using contrast enhanced computed tomography, color Doppler ultrasonography and contrast enhanced ultrasonography with Sonazoid. All the sentinel lymph nodes were identified, and the sentinel lymph nodes detected by contrast enhanced ultrasonography with Sonazoid corresponded with those detected by computed tomography lymphography and indigo carmine method. The detection of metastasis based on contrast enhanced computed tomography were sensitivity 20.0 %, specificity 88.2 %, PPV 60.0 %, NPV 55.6 %, accuracy 56.3 %. Based on color Doppler ultrasonography, the results were sensitivity 36.4 %, specificity 95.2 %, PPV 80.0 %, NPV 74.1 %, accuracy 75.0 %. Based on contrast enhanced ultrasonography with Sonazoid, the results were sensitivity 81.8 %, specificity 95.2 %, PPV 90.0 %, NPV 90.9 %, accuracy 90.6 %. The results suggested that contrast enhanced ultrasonography with Sonazoid was the most accurate among the evaluations of these modalities. In the future, we believe that our method would take the place of conventional sentinel lymph node biopsy for an axillary staging method.", "classifications": [ { "id": "Suzuki", "label": "Group Suzuki", "parent": "Takekawa", "type": "group" }, { "id": "Takekawa", "label": "Team Takekawa", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Fumihiko", "last_name": "Matsuzawa", "name": null }, { "creator_type": "author", "first_name": "Kiyoka", "last_name": "Omoto", "name": null }, { "creator_type": "author", "first_name": "Takahiro", "last_name": "Einama", "name": null }, { "creator_type": "author", "first_name": "Hironori", "last_name": "Abe", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Jun", "last_name": "Hamaguchi", "name": null }, { "creator_type": "author", "first_name": "Terumi", "last_name": "Kaga", "name": null }, { "creator_type": "author", "first_name": "Mami", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Masako", "last_name": "Oomura", "name": null }, { "creator_type": "author", "first_name": "Yumiko", "last_name": "Takata", "name": null }, { "creator_type": "author", "first_name": "Ayako", "last_name": "Fujibe", "name": null }, { "creator_type": "author", "first_name": "Chie", "last_name": "Takeda", "name": null }, { "creator_type": "author", "first_name": "Etsuya", "last_name": "Tamura", "name": null }, { "creator_type": "author", "first_name": "Akinobu", "last_name": "Taketomi", "name": null }, { "creator_type": "author", "first_name": "Kenichi", "last_name": "Kyuno", "name": null } ], "identifiers": { "doi": { "normalized": "10.1186/s40064-015-1291-1" }, "pmcid": { "normalized": "PMC4573976" }, "pmid": { "normalized": "26405629" } }, "mesh": [], "publication": { "conference_name": null, "date": "2015", "date_precision": "year", "issue": "", "normalized_date": "2015", "pages": "509", "proceedings_title": null, "publisher": "", "title": "SpringerPlus", "volume": "4", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "Accurate evaluation of axillary sentinel lymph node metastasis using contrast-enhanced ultrasonography with Sonazoid in breast cancer: a preliminary clinical trial.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "4H-1-benzopyran-4-ones (chromones) are important naturally-distributing compounds. As compared with flavones, isoflavones and 2-styrylchromones, there are only few papers of 3-styrylchromones that have been published. We have previously reported that among fifteen 3-styrylchromone derivatives, three new synthetic compounds that have OCH(3) group at the C-6 position of chromone ring, (E)-3-(4-hydroxystyryl)-6-methoxy-4H-chromen-4-one (compound 11), (E)-6-methoxy-3-(4-methoxystyryl)-4H-chromen-4-one (compound 4), (E)-6-methoxy-3-(3,4,5-trimethoxystyryl)-4H-chromen-4-one (compound 6) showed much higher cytotoxicities against four epithelial human oral squamous cell carcinoma (OSCC) lines than human normal oral mesenchymal cells. In order to further confirm the tumor specificities of these compounds, we compared their cytotoxicities against both human epithelial malignant and non-malignant cells, and then investigated their effects on fine cell structures and metabolic profiles and cell death in human OSCC cell line HSC-2. Cytotoxicities of compounds 4, 6, 11 were assayed with MTT method. Fine cell structures were observed under transmission electron microscope. Cellular metabolites were extracted with methanol and subjected to CE-TOFMS analysis. Compounds 4, 6, 11 showed much weaker cytotoxicity against human oral keratinocyte and primary human gingival epithelial cells, as compared with HSC-2, confirming their tumor-specificity, whereas doxorubicin and 5-FU were highly cytotoxic to these normal epithelial cells, giving unexpectedly lower tumor-specificity. The most cytotoxic compound 11, induced the mitochondrial vacuolization, autophagy suppression followed by apoptosis induction, and changes in the metabolites involved in amino acid and glycerophospholipid metabolisms. Chemical modification of lead compound 11 may be a potential choice for designing new type of anticancer drugs.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Sakagami", "name": null }, { "creator_type": "author", "first_name": "Chiyako", "last_name": "Shimada", "name": null }, { "creator_type": "author", "first_name": "Yumiko", "last_name": "Kanda", "name": null }, { "creator_type": "author", "first_name": "Osamu", "last_name": "Amano", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Sugimoto", "name": null }, { "creator_type": "author", "first_name": "Sana", "last_name": "Ota", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Masaru", "last_name": "Tomita", "name": null }, { "creator_type": "author", "first_name": "Akira", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Sei-Ichi", "last_name": "Tanuma", "name": null }, { "creator_type": "author", "first_name": "Koichi", "last_name": "Takao", "name": null }, { "creator_type": "author", "first_name": "Yoshiaki", "last_name": "Sugita", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.toxrep.2015.09.009" }, "pmcid": { "normalized": "PMC5598371" }, "pmid": { "normalized": "28962471" } }, "mesh": [], "publication": { "conference_name": null, "date": "2015", "date_precision": "year", "issue": "", "normalized_date": "2015", "pages": "1281-1290", "proceedings_title": null, "publisher": "", "title": "Toxicology reports", "volume": "2", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "Effects of 3-styrylchromones on metabolic profiles and cell death in oral squamous cell carcinoma cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The calcium (Ca(2+))-paradox injury of the heart, induced by restoration of extracellular Ca(2+) after its short-term depletion, is known to provoke cardiomyocyte contracture. However, undetermined is how the Ca(2+)-paradox provokes such a distinctive presentation of myocytes in the heart. To address this, we imaged sequential intracellular Ca(2+) dynamics and concomitant structures of the subepicardial ventricular myocytes in fluo3-loaded, Langendorff-perfused rat hearts produced by the Ca(2+) paradox. Under rapid-scanning confocal microscopy, repletion of Ca(2+) following its depletion produced high-frequency Ca(2+) waves in individual myocytes with asynchronous localized contractions, resulting in contracture within 10 min. Such alterations of myocytes were attenuated by 5-mM NiCl2, but not by verapamil, SEA0400, or combination of ryanodine and thapsigargin, indicating a contribution of non-specific transmembrane Ca(2+) influx in the injury. However, saponin-induced membrane permeabilization of Ca(2+) showed no apparent contracture despite the emergence of high-frequency Ca(2+) waves, indicating an essential role of myocyte-myocyte and myocyte-extracellular matrix (ECM) mechanical connections in the Ca(2+) paradox. In immunohistochemistry Ca(2+) depletion produced separation of the intercalated disc that expresses cadherin and dissipation of beta-dystroglycan located along the sarcolemma. Taken together, along with the trans-sarcolemmal Ca(2+) influx, disruption of cell-cell and cell-ECM connections is essential for contracture in the Ca(2+)-paradox injury.", "classifications": [ { "id": "Tanaka", "label": "Group Tanaka", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Hiroki", "last_name": "Mani", "name": null }, { "creator_type": "author", "first_name": "Hideo", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Tetsuya", "last_name": "Adachi", "name": null }, { "creator_type": "author", "first_name": "Masaya", "last_name": "Ikegawa", "name": null }, { "creator_type": "author", "first_name": "Ping", "last_name": "Dai", "name": null }, { "creator_type": "author", "first_name": "Naohisa", "last_name": "Fujita", "name": null }, { "creator_type": "author", "first_name": "Tetsuro", "last_name": "Takamatsu", "name": null } ], "identifiers": { "doi": { "normalized": "10.1267/ahc.14059" }, "pmcid": { "normalized": "PMC4387258" }, "pmid": { "normalized": "25861132" } }, "mesh": [], "publication": { "conference_name": null, "date": "2015", "date_precision": "year", "issue": "1", "normalized_date": "2015", "pages": "1-8", "proceedings_title": null, "publisher": "", "title": "Acta histochemica et cytochemica", "volume": "48", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "How Does the Ca(2+)-paradox Injury Induce Contracture in the Heart?-A Combined Study of the Intracellular Ca(2+) Dynamics and Cell Structures in Perfused Rat Hearts.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Using Raman spectral imaging, we visualized the cell state transition during differentiation and constructed hypothetical potential landscapes for attractors of cellular states on a state space composed of parameters related to the shape of the Raman spectra. As models of differentiation, we used the myogenic C2C12 cell line and mouse embryonic stem cells. Raman spectral imaging can validate the amounts and locations of multiple cellular components that describe the cell state such as proteins, nucleic acids, and lipids; thus, it can report the state of a single cell. Herein, we visualized the cell state transition during differentiation using Raman spectral imaging of cell nuclei in combination with principal component analysis. During differentiation, cell populations with a seemingly homogeneous cell state before differentiation showed heterogeneity at the early stage of differentiation. At later differentiation stages, the cells returned to a homogeneous cell state that was different from the undifferentiated state. Thus, Raman spectral imaging enables us to illustrate the disappearance and reappearance of an attractor in a differentiation landscape, where cells stochastically fluctuate between states at the early stage of differentiation.", "classifications": [ { "id": "Fujita", "label": "Group Fujita", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Taro", "last_name": "Ichimura", "name": null }, { "creator_type": "author", "first_name": "Liang-da", "last_name": "Chiu", "name": null }, { "creator_type": "author", "first_name": "Katsumasa", "last_name": "Fujita", "name": null }, { "creator_type": "author", "first_name": "Hiroaki", "last_name": "Machiyama", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Kawata", "name": null }, { "creator_type": "author", "first_name": "Tomonobu M.", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Hideaki", "last_name": "Fujita", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/srep11358" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "26079396" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": true }, { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "Embryonic Stem Cells", "descriptor_ui": "D053595", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Muscle Development", "descriptor_ui": "D024510", "major_topic": false }, { "descriptor": "Myoblasts", "descriptor_ui": "D032446", "major_topic": false }, { "descriptor": "Spectrum Analysis, Raman", "descriptor_ui": "D013059", "major_topic": true } ], "publication": { "conference_name": null, "date": "2015", "date_precision": "year", "issue": "", "normalized_date": "2015", "pages": "", "proceedings_title": null, "publisher": "", "title": "Scientific Reports", "volume": "5", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "Visualizing the appearance and disappearance of the attractor of differentiation using Raman spectral imaging.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "During morphogenesis, various cellular activities are spatiotemporally coordinated on the protein regulatory background to construct the complicated, three-dimensional (3D) structures of organs. Computational simulations using 3D vertex models have been the focus of efforts to approach the mechanisms underlying 3D multicellular constructions, such as dynamics of the 3D monolayer or multilayer cell sheet like epithelia as well as the 3D compacted cell aggregate, including dynamic changes in layer structures. 3D vertex models enable the quantitative simulation of multicellular morphogenesis on the basis of single-cell mechanics, with complete control of various cellular activities such as cell contraction, growth, rearrangement, division, and death. This review describes the general use of the 3D vertex model, along with its applications to several simplified problems of developmental phenomena.", "classifications": [ { "id": "Okuda", "label": "Group Okuda", "parent": "Imayoshi", "type": "group" }, { "id": "Imayoshi", "label": "Team Imayoshi", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Satoru", "last_name": "Okuda", "name": null }, { "creator_type": "author", "first_name": "Yasuhiro", "last_name": "Inoue", "name": null }, { "creator_type": "author", "first_name": "Taiji", "last_name": "Adachi", "name": null } ], "identifiers": { "doi": { "normalized": "10.2142/biophysico.12.0_13" }, "pmcid": { "normalized": "PMC4736843" }, "pmid": { "normalized": "27493850" } }, "mesh": [], "publication": { "conference_name": null, "date": "2015", "date_precision": "year", "issue": "", "normalized_date": "2015", "pages": "13-20", "proceedings_title": null, "publisher": "", "title": "Biophysics and physicobiology", "volume": "12", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "Three-dimensional vertex model for simulating multicellular morphogenesis.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The transient receptor potential (TRP) proteins are a family of ion channels that act as cellular sensors as well as signal integrators. Several members of the TRP family are sensitive to changes in cellular redox status. Among them, TRPA1 is remarkably susceptible to various oxidants and is known to mediate neuropathic pain and respiratory, vascular, and gastrointestinal functions, making TRPA1 an attractive therapeutic target. However, a method to achieve selective modulation of TRPA1 by small molecules has not yet been established. Most recently, we found that a novel N-nitrosamine compound activates TRPA1 by S-nitrosylation (the addition of a nitric oxide (NO) group to cysteine thiol) and does so with significant selectivity over other NO-sensitive TRP channels. It is proposed that this subtype selectivity is conferred through synergistic effects of electrophilic cysteine transnitrosylation and molecular recognition of the non-electrophilic moiety on the N-nitrosamine. On the other hand, TRPCs are typical receptor-activated Ca(2+)-permeable cation channels, which sense messenger molecules generated downstream of phospholipase activation. Previously, activation of TRPC3 and TRPC6 by diacylglycerol has been reported to play important roles in the pathogenesis of cardiac hypertrophy. Also, a pyrazole compound, Pyr3, which selectively inhibits TRPC3, suppresses cardiac hypertrophy in animal models in vitro and in vivo. We have most recently found that Pyr3 and related compounds are effective in suppressing cardiac fibrosis and ischemia responsible for cardiac remodeling as well. Thus, in this chapter, we describe the molecular pharmacology of TRP modulators and discuss their modulatory mechanisms and pharmacological actions.", "classifications": [ { "id": "Nishida", "label": "Group Nishida", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "editor", "first_name": "Kazuwa", "last_name": "Nakao", "name": null }, { "creator_type": "editor", "first_name": "Nagahiro", "last_name": "Minato", "name": null }, { "creator_type": "editor", "first_name": "Shinji", "last_name": "Uemoto", "name": null }, { "creator_type": "author", "first_name": "Motohiro", "last_name": "Nishida", "name": null }, { "creator_type": "author", "first_name": "Koichiro", "last_name": "Kuwahara", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Kozai", "name": null }, { "creator_type": "author", "first_name": "Reiko", "last_name": "Sakaguchi", "name": null }, { "creator_type": "author", "first_name": "Yasuo", "last_name": "Mori", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/978-4-431-55651-0_17" }, "pmcid": { "normalized": null }, "pmid": { "normalized": null } }, "mesh": [], "publication": { "conference_name": null, "date": "2015", "date_precision": "year", "issue": null, "normalized_date": "2015", "pages": "195-218", "proceedings_title": null, "publisher": "Springer", "title": null, "volume": "", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "TRP Channels: Their Function and Potentiality as Drug Targets.", "url": "", "zotero": { "item_type": "bookSection" } }, { "abstract": "Hot spring water and natural mineral water have been therapeutically used to prevent or improve various diseases. Specifically, consumption of bicarbonate-rich mineral water (BMW) has been reported to prevent or improve type 2 diabetes (T2D) in humans. However, the molecular mechanisms of the beneficial effects behind mineral water consumption remain unclear. To elucidate the molecular level effects of BMW consumption on glycemic control, blood metabolome analysis and fecal microbiome analysis were applied to the BMW consumption test. During the study, 19 healthy volunteers drank 500 mL of commercially available tap water (TW) or BMW daily. TW consumption periods and BMW consumption periods lasted for a week each and this cycle was repeated twice. Biochemical tests indicated that serum glycoalbumin levels, one of the indexes of glycemic controls, decreased significantly after BMW consumption. Metabolome analysis of blood samples revealed that 19 metabolites including glycolysis-related metabolites and 3 amino acids were significantly different between TW and BMW consumption periods. Additionally, microbiome analysis demonstrated that composition of lean-inducible bacteria was increased after BMW consumption. Our results suggested that consumption of BMW has the possible potential to prevent and/or improve T2D through the alterations of host metabolism and gut microbiota composition.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Shinnosuke", "last_name": "Murakami", "name": null }, { "creator_type": "author", "first_name": "Yasuaki", "last_name": "Goto", "name": null }, { "creator_type": "author", "first_name": "Kyo", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Hayasaka", "name": null }, { "creator_type": "author", "first_name": "Shigeo", "last_name": "Kurihara", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Masaru", "last_name": "Tomita", "name": null }, { "creator_type": "author", "first_name": "Shinji", "last_name": "Fukuda", "name": null } ], "identifiers": { "doi": { "normalized": "10.1155/2015/824395" }, "pmcid": { "normalized": "PMC4698932" }, "pmid": { "normalized": "26798400" } }, "mesh": [], "publication": { "conference_name": null, "date": "2015", "date_precision": "year", "issue": "", "normalized_date": "2015", "pages": "824395", "proceedings_title": null, "publisher": "", "title": "Evidence-based complementary and alternative medicine : eCAM", "volume": "2015", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "The Consumption of Bicarbonate-Rich Mineral Water Improves Glycemic Control.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Mumps viruses show diverse cytopathic effects (CPEs) of infected cells and viral plaque formation (no CPE or no plaque formation in some cases) depending on the viral strain, highlighting the difficulty in mumps laboratory studies. In our previous study, a new sialidase substrate, 2-(benzothiazol-2-yl)-4-bromophenyl 5-acetamido-3,5-dideoxy-α-D-glycero-D-galacto-2-nonulopyranosidonic acid (BTP3-Neu5Ac), was developed for visualization of sialidase activity. BTP3-Neu5Ac can easily and rapidly perform histochemical fluorescent visualization of influenza viruses and virus-infected cells without an antiviral antibody and cell fixation. In the present study, the potential utility of BTP3-Neu5Ac for rapid detection of mumps virus was demonstrated. BTP3-Neu5Ac could visualize dot-blotted mumps virus, virus-infected cells, and plaques (plaques should be called focuses due to staining of infected cells in this study), even if a CPE was not observed. Furthermore, virus cultivation was possible by direct pick-up from a fluorescent focus. In conventional methods, visible appearance of the CPE and focuses often requires more than 6 days after infection, but the new method with BTP3-Neu5Ac clearly visualized infected cells after 2 days and focuses after 4 days. The BTP3-Neu5Ac assay is a precise, easy, and rapid assay for confirmation and titration of mumps virus.", "classifications": [ { "id": "Suzuki", "label": "Group Suzuki", "parent": "Takekawa", "type": "group" }, { "id": "Takekawa", "label": "Team Takekawa", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Tadanobu", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Agarikuchi", "name": null }, { "creator_type": "author", "first_name": "Yuuki", "last_name": "Kurebayashi", "name": null }, { "creator_type": "author", "first_name": "Nona", "last_name": "Shibahara", "name": null }, { "creator_type": "author", "first_name": "Chihiro", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Akiko", "last_name": "Kishikawa", "name": null }, { "creator_type": "author", "first_name": "Keijo", "last_name": "Fukushima", "name": null }, { "creator_type": "author", "first_name": "Maiko", "last_name": "Takano", "name": null }, { "creator_type": "author", "first_name": "Fumie", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Hirohisa", "last_name": "Wada", "name": null }, { "creator_type": "author", "first_name": "Tadamune", "last_name": "Otsubo", "name": null }, { "creator_type": "author", "first_name": "Kiyoshi", "last_name": "Ikeda", "name": null }, { "creator_type": "author", "first_name": "Akira", "last_name": "Minami", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Suzuki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1371/journal.pone.0144038" }, "pmcid": { "normalized": "PMC4668055" }, "pmid": { "normalized": "26629699" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Chlorocebus aethiops", "descriptor_ui": "D002522", "major_topic": false }, { "descriptor": "Fluorescence", "descriptor_ui": "D005453", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mumps virus", "descriptor_ui": "D009109", "major_topic": false }, { "descriptor": "Vero Cells", "descriptor_ui": "D014709", "major_topic": false } ], "publication": { "conference_name": null, "date": "2015", "date_precision": "year", "issue": "12", "normalized_date": "2015", "pages": "e0144038", "proceedings_title": null, "publisher": "", "title": "PloS one", "volume": "10", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "Easy and Rapid Detection of Mumps Virus by Live Fluorescent Visualization of Virus-Infected Cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The basic-helix-loop-helix (bHLH) transcription factors Ascl1/Mash1, Hes1, and Olig2 regulate the fate choice of neurons, astrocytes, and oligodendrocytes, respectively; however, these factors are coexpressed in self-renewing multipotent neural stem cells (NSCs) even before cell fate determination. This fact raises the possibility that these fate determination factors are differentially expressed between self-renewing and differentiating NSCs with unique expression dynamics. Real-time imaging analysis utilizing fluorescent proteins is a powerful strategy for monitoring expression dynamics. Fusion with fluorescent reporters makes it possible to analyze the dynamic behavior of specific proteins in living cells. However, it is technically challenging to conduct long-term imaging of proteins, particularly those with low expression levels, because a high-sensitivity and low-noise imaging system is required, and very often bleaching of fluorescent proteins and cell toxicity by prolonged laser exposure are problematic. Furthermore, to analyze the functional roles of the dynamic expression of cellular proteins, it is essential to image reporter fusion proteins that are expressed at comparable levels to their endogenous expression. In this review, we introduce our recent reports about the dynamic control of bHLH transcription factors in multipotency and fate choice of NSCs, focusing on real-time imaging of fluorescent reporters fused with bHLH transcription factors. Our imaging results indicate that bHLH transcription factors are expressed in an oscillatory manner by NSCs, and that one of them becomes dominant during fate choice. We propose that the multipotent state of NSCs correlates with the oscillatory expression of several bHLH transcription factors, whereas the differentiated state correlates with the sustained expression of a single bHLH transcription factor.", "classifications": [ { "id": "Imayoshi", "label": "Group Imayoshi", "parent": "Imayoshi", "type": "group" }, { "id": "Imayoshi", "label": "Team Imayoshi", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Itaru", "last_name": "Imayoshi", "name": null }, { "creator_type": "author", "first_name": "Fumiyoshi", "last_name": "Ishidate", "name": null }, { "creator_type": "author", "first_name": "Ryoichiro", "last_name": "Kageyama", "name": null } ], "identifiers": { "doi": { "normalized": "10.3389/fncel.2015.00288" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "26300726" } }, "mesh": [], "publication": { "conference_name": null, "date": "2015", "date_precision": "year", "issue": "", "normalized_date": "2015", "pages": "", "proceedings_title": null, "publisher": "", "title": "Frontiers in Cellular Neuroscience", "volume": "9", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "Real-time imaging of bHLH transcription factors reveals their dynamic control in the multipotency and fate choice of neural stem cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Protein components of cell adhesion machinery show continuous renewal even in the static state of epithelial cells and participate in the formation and maintenance of normal epithelial architecture and tumor suppression. CADM1 is a tumor suppressor belonging to the immunoglobulin superfamily of cell adhesion molecule and forms a cell adhesion complex with an actin-binding protein, 4.1B, and a scaffold protein, MPP3, in the cytoplasm. Here, we investigate dynamic regulation of the CADM1-4.1B-MPP3 complex in mature cell adhesion by fluorescence recovery after photobleaching (FRAP) analysis. Traditional FRAP analysis were performed for relatively short period of around 10min. Here, thanks to recent advances in the sensitive laser detector systems, we examine FRAP of CADM1 complex for longer period of 60 min and analyze the recovery with exponential curve-fitting to distinguish the fractions with different diffusion constants. This approach reveals that the fluorescence recovery of CADM1 is fitted to a single exponential function with a time constant (τ) of approximately 16 min, whereas 4.1B and MPP3 are fitted to a double exponential function with two τs of approximately 40-60 sec and 16 min. The longer τ is similar to that of CADM1, suggesting that 4.1B and MPP3 have two distinct fractions, one forming a complex with CADM1 and the other present as a free pool. Fluorescence loss in photobleaching analysis supports the presence of a free pool of these proteins near the plasma membrane. Furthermore, double exponential fitting makes it possible to estimate the ratio of 4.1B and MPP3 present as a free pool and as a complex with CADM1 as approximately 3:2 and 3:1, respectively. Our analyses reveal a central role of CADM1 in stabilizing the complex with 4.1B and MPP3 and provide insight in the dynamics of adhesion complex formation.", "classifications": [ { "id": "Suzuki", "label": "Group Suzuki", "parent": "Takekawa", "type": "group" }, { "id": "Takekawa", "label": "Team Takekawa", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Mika", "last_name": "Sakurai-Yageta", "name": null }, { "creator_type": "author", "first_name": "Tomoko", "last_name": "Maruyama", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Kazuhisa", "last_name": "Ichikawa", "name": null }, { "creator_type": "author", "first_name": "Yoshinori", "last_name": "Murakami", "name": null } ], "identifiers": { "doi": { "normalized": "10.1371/journal.pone.0116637" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "25780926" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Binding Sites", "descriptor_ui": "D001665", "major_topic": false }, { "descriptor": "Cell Adhesion", "descriptor_ui": "D002448", "major_topic": false }, { "descriptor": "Cell Adhesion Molecule-1", "descriptor_ui": "D000075982", "major_topic": false }, { "descriptor": "Cell Adhesion Molecules", "descriptor_ui": "D015815", "major_topic": false }, { "descriptor": "Dogs", "descriptor_ui": "D004285", "major_topic": false }, { "descriptor": "Epithelial Cells", "descriptor_ui": "D004847", "major_topic": false }, { "descriptor": "Fluorescence Recovery After Photobleaching", "descriptor_ui": "D036681", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Immunoglobulins", "descriptor_ui": "D007136", "major_topic": false }, { "descriptor": "Kinetics", "descriptor_ui": "D007700", "major_topic": false }, { "descriptor": "Madin Darby Canine Kidney Cells", "descriptor_ui": "D061985", "major_topic": false }, { "descriptor": "Microfilament Proteins", "descriptor_ui": "D008840", "major_topic": false }, { "descriptor": "Movement", "descriptor_ui": "D009068", "major_topic": false }, { "descriptor": "Nuclear Proteins", "descriptor_ui": "D009687", "major_topic": false }, { "descriptor": "Protein Stability", "descriptor_ui": "D055550", "major_topic": false }, { "descriptor": "Transcription Factors", "descriptor_ui": "D014157", "major_topic": false } ], "publication": { "conference_name": null, "date": "2015", "date_precision": "year", "issue": "3", "normalized_date": "2015", "pages": "", "proceedings_title": null, "publisher": "", "title": "PLoS ONE", "volume": "10", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "Dynamic Regulation of a Cell Adhesion Protein Complex Including CADM1 by Combinatorial Analysis of FRAP with Exponential Curve-Fitting.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Unlike bacteria such as Escherichia coli and Bacillus subtilis, several species of freshwater cyanobacteria are known to contain multiple chromosomal copies per cell, at all stages of their cell cycle. We have characterized the replication of multi-copy chromosomes in the cyanobacterium Synechococcus elongatus PCC 7942 (hereafter Synechococcus 7942). In Synechococcus 7942, the replication of multi-copy chromosome is asynchronous, not only among cells but also among multi-copy chromosomes. This suggests that DNA replication is not tightly coupled to cell division in Synechococcus 7942. To address this hypothesis, we analysed the relationship between DNA replication and cell doubling at various growth phases of Synechococcus 7942 cell culture. Three distinct growth phases were characterised in Synechococcus 7942 batch culture: lag phase, exponential phase, and arithmetic (linear) phase. The chromosomal copy number was significantly higher during the lag phase than during the exponential and linear phases. Likewise, DNA replication activity was higher in the lag phase cells than in the exponential and linear phase cells, and the lag phase cells were more sensitive to nalidixic acid, a DNA gyrase inhibitor, than cells in other growth phases. To elucidate physiological differences in Synechococcus 7942 during the lag phase, we analysed the metabolome at each growth phase. In addition, we assessed the accumulation of central carbon metabolites, amino acids, and DNA precursors at each phase. The results of these analyses suggest that Synechococcus 7942 cells prepare for cell division during the lag phase by initiating intensive chromosomal DNA replication and accumulating metabolites necessary for the subsequent cell division and elongation steps that occur during the exponential growth and linear phases.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Satoru", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Ryudo", "last_name": "Ohbayashi", "name": null }, { "creator_type": "author", "first_name": "Yu", "last_name": "Kanesaki", "name": null }, { "creator_type": "author", "first_name": "Natsumi", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Taku", "last_name": "Chibazakura", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Hirofumi", "last_name": "Yoshikawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1371/journal.pone.0136800" }, "pmcid": { "normalized": "PMC4558043" }, "pmid": { "normalized": "26331851" } }, "mesh": [ { "descriptor": "Chromosomes, Bacterial", "descriptor_ui": "D002876", "major_topic": false }, { "descriptor": "DNA Replication", "descriptor_ui": "D004261", "major_topic": true }, { "descriptor": "DNA, Bacterial", "descriptor_ui": "D004269", "major_topic": false }, { "descriptor": "Metabolome", "descriptor_ui": "D055442", "major_topic": false }, { "descriptor": "Synechococcus", "descriptor_ui": "D046940", "major_topic": false } ], "publication": { "conference_name": null, "date": "2015", "date_precision": "year", "issue": "9", "normalized_date": "2015", "pages": "e0136800", "proceedings_title": null, "publisher": "", "title": "PloS one", "volume": "10", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "Intensive DNA Replication and Metabolism during the Lag Phase in Cyanobacteria.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Fluorescence lifetime imaging (FLIM) has been recognized as a powerful microscopy technique to examine environments in living systems. The fluorescence lifetime does not depend on the photobleaching and optical conditions, which allows us to obtain quantitative information on intracellular environments by analyzing the fluorescence lifetime. A variety of exogenous fluorophores have been applied in FLIM measurements to examine cellular processes. Information on the correlation between the fluorescence lifetime and the physiological parameters is essential to elucidate the cellular environments from the fluorescence lifetime measurements of exogenous fluorophores. In this review, exogenous fluorophores used for lifetime-based sensing are summarized, with the expectation that it becomes a basis for selecting the fluorophore used to investigate the intracellular environment with FLIM. Experimental results of the intracellular sensing of pH, metal ions, oxygen, viscosity, and other physiological parameters on the basis of the FLIM measurements are described along with a brief explanation of the mechanism of the change in the fluorescence lifetime.", "classifications": [ { "id": "Nakabayashi", "label": "Group Nakabayashi", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Takakazu", "last_name": "Nakabayashi", "name": null }, { "creator_type": "author", "first_name": "Nobuhiro", "last_name": "Ohta", "name": null } ], "identifiers": { "doi": { "normalized": "10.2116/analsci.31.275" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "25864670" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Fluorescent Dyes", "descriptor_ui": "D005456", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Intracellular Space", "descriptor_ui": "D042541", "major_topic": false }, { "descriptor": "Luminescent Proteins", "descriptor_ui": "D008164", "major_topic": false }, { "descriptor": "Nanostructures", "descriptor_ui": "D049329", "major_topic": false }, { "descriptor": "Optical Imaging", "descriptor_ui": "D061848", "major_topic": false } ], "publication": { "conference_name": null, "date": "2015", "date_precision": "year", "issue": "4", "normalized_date": "2015", "pages": "275-285", "proceedings_title": null, "publisher": "", "title": "Analytical sciences : the international journal of the Japan Society for Analytical Chemistry", "volume": "31", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "Sensing of intracellular environments by fluorescence lifetime imaging of exogenous fluorophores.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Background: In genome-wide studies, over-representation analysis (ORA) against a set of genes is an essential step for biological interpretation. Many gene annotation resources and software platforms for ORA have been proposed. Recently, Medical Subject Headings (MeSH) terms, which are annotations of PubMed documents, have been used for ORA. MeSH enables the extraction of broader meaning from the gene lists and is expected to become an exhaustive annotation resource for ORA. However, the existing MeSH ORA software platforms are still not sufficient for several reasons. Results: In this work, we developed an original MeSH ORA framework composed of six types of R packages, including MeSH.db, MeSH.AOR.db, MeSH.PCR.db, the org.MeSH.XXX.db-type packages, MeSHDbi, and meshr. Conclusions: Using our framework, users can easily conduct MeSH ORA. By utilizing the enriched MeSH terms, related PubMed documents can be retrieved and saved on local machines within this framework. Electronic supplementary material: The online version of this article (doi:10.1186/s12859-015-0453-z) contains supplementary material, which is available to authorized users.", "classifications": [ { "id": "Nikaido", "label": "Group Nikaido", "parent": "Fujiwara", "type": "group" }, { "id": "Fujiwara", "label": "Team Fujiwara", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Koki", "last_name": "Tsuyuzaki", "name": null }, { "creator_type": "author", "first_name": "Gota", "last_name": "Morota", "name": null }, { "creator_type": "author", "first_name": "Manabu", "last_name": "Ishii", "name": null }, { "creator_type": "author", "first_name": "Takeru", "last_name": "Nakazato", "name": null }, { "creator_type": "author", "first_name": "Satoru", "last_name": "Miyazaki", "name": null }, { "creator_type": "author", "first_name": "Itoshi", "last_name": "Nikaido", "name": null } ], "identifiers": { "doi": { "normalized": "10.1186/s12859-015-0453-z" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "25887539" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Caloric Restriction", "descriptor_ui": "D031204", "major_topic": false }, { "descriptor": "Computational Biology", "descriptor_ui": "D019295", "major_topic": false }, { "descriptor": "Gene Expression Profiling", "descriptor_ui": "D020869", "major_topic": false }, { "descriptor": "Genome-Wide Association Study", "descriptor_ui": "D055106", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Information Storage and Retrieval", "descriptor_ui": "D016247", "major_topic": false }, { "descriptor": "Medical Subject Headings", "descriptor_ui": "D046650", "major_topic": true }, { "descriptor": "Molecular Sequence Annotation", "descriptor_ui": "D058977", "major_topic": true }, { "descriptor": "Oligonucleotide Array Sequence Analysis", "descriptor_ui": "D020411", "major_topic": false }, { "descriptor": "Pseudomonas aeruginosa", "descriptor_ui": "D011550", "major_topic": false }, { "descriptor": "PubMed", "descriptor_ui": "D039781", "major_topic": true }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Software", "descriptor_ui": "D012984", "major_topic": true }, { "descriptor": "Vocabulary, Controlled", "descriptor_ui": "D018875", "major_topic": true } ], "publication": { "conference_name": null, "date": "2015", "date_precision": "year", "issue": "", "normalized_date": "2015", "pages": "", "proceedings_title": null, "publisher": "", "title": "BMC Bioinformatics", "volume": "16", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "MeSH ORA framework: R/Bioconductor packages to support MeSH over-representation analysis.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Although successful fertilization depends on timely encounters between sperm and egg, the decoupling of mating and fertilization often confers reproductive advantages to internally fertilizing animals. In several vertebrate groups, postcopulatory sperm viability is prolonged by storage in specialized organs within the female reproductive tract. In birds, ejaculated sperm can be stored in a quiescent state within oviductal sperm storage tubules (SSTs), thereby retaining fertilizability for up to 15 weeks at body temperature (41 °C); however, the mechanism by which motile sperm become quiescent within SSTs is unknown. Here, we show that low oxygen and high lactic acid concentrations are established in quail SSTs. Flagellar quiescence was induced by lactic acid in the concentration range found in SSTs through flagellar dynein ATPase inactivation following cytoplasmic acidification (/=25 kg/m(2) and <25 kg/m(2)) to investigate an interaction between genotypes and obesity. RESULTS: The A/G and A/A genotypes of BMAL2 rs7958822 showed significantly higher adjusted odds ratios (OR) for T2DM than the G/G genotype among obese men (OR=2.2, 95% confidence intervals [CI] 1.1, 4.6, P for interaction=0.0495) and obese women (OR=2.7, 95% CI 1.1, 6.7, P for interaction=0.199). There were no significant associations between BMAL1 rs11022775 or rs2290035 genotypes and T2DM. CONCLUSIONS: To the best of our knowledge, this is the first study to show the significant association between BMAL2 rs7958822 genotype and T2DM among obese subjects.", "classifications": [ { "id": "Tanaka", "label": "Group Tanaka", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Miwa", "last_name": "Yamaguchi", "name": null }, { "creator_type": "author", "first_name": "Hirokazu", "last_name": "Uemura", "name": null }, { "creator_type": "author", "first_name": "Kokichi", "last_name": "Arisawa", "name": null }, { "creator_type": "author", "first_name": "Sakurako", "last_name": "Katsuura-Kamano", "name": null }, { "creator_type": "author", "first_name": "Nobuyuki", "last_name": "Hamajima", "name": null }, { "creator_type": "author", "first_name": "Asahi", "last_name": "Hishida", "name": null }, { "creator_type": "author", "first_name": "Shino", "last_name": "Suma", "name": null }, { "creator_type": "author", "first_name": "Isao", "last_name": "Oze", "name": null }, { "creator_type": "author", "first_name": "Kazuyo", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Naoyuki", "last_name": "Takashima", "name": null }, { "creator_type": "author", "first_name": "Sadao", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Rie", "last_name": "Ibusuki", "name": null }, { "creator_type": "author", "first_name": "Haruo", "last_name": "Mikami", "name": null }, { "creator_type": "author", "first_name": "Keizo", "last_name": "Ohnaka", "name": null }, { "creator_type": "author", "first_name": "Nagato", "last_name": "Kuriyama", "name": null }, { "creator_type": "author", "first_name": "Michiaki", "last_name": "Kubo", "name": null }, { "creator_type": "author", "first_name": "Hideo", "last_name": "Tanaka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.diabres.2015.10.009" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "26497775" } }, "mesh": [ { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "ARNTL Transcription Factors", "descriptor_ui": "D056930", "major_topic": false }, { "descriptor": "Body Mass Index", "descriptor_ui": "D015992", "major_topic": false }, { "descriptor": "Cohort Studies", "descriptor_ui": "D015331", "major_topic": false }, { "descriptor": "Cross-Sectional Studies", "descriptor_ui": "D003430", "major_topic": false }, { "descriptor": "Diabetes Mellitus, Type 2", "descriptor_ui": "D003924", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Gene-Environment Interaction", "descriptor_ui": "D059647", "major_topic": false }, { "descriptor": "Genotype", "descriptor_ui": "D005838", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Japan", "descriptor_ui": "D007564", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Obesity", "descriptor_ui": "D009765", "major_topic": false }, { "descriptor": "Odds Ratio", "descriptor_ui": "D016017", "major_topic": false }, { "descriptor": "Polymorphism, Single Nucleotide", "descriptor_ui": "D020641", "major_topic": true }, { "descriptor": "Prevalence", "descriptor_ui": "D015995", "major_topic": false } ], "publication": { "conference_name": null, "date": "2015 Dec", "date_precision": "unknown", "issue": "3", "normalized_date": null, "pages": "301-308", "proceedings_title": null, "publisher": "", "title": "Diabetes research and clinical practice", "volume": "110", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "Association between brain-muscle-ARNT-like protein-2 (BMAL2) gene polymorphism and type 2 diabetes mellitus in obese Japanese individuals: A cross-sectional analysis of the Japan Multi-institutional Collaborative Cohort Study.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Fluorescence spectra and fluorescence lifetime images of talaporfin sodium and sodium-pheophorbide a, which can be regarded as photosensitizers for photodynamic therapy, were measured in normal and cancer cells. The reduction of the fluorescence intensity by photoirradiation was observed for both photosensitizers in both cells, but the quenching rate was much faster in cancer cells than in normal cells. These results are explained in terms of the excessive generation of reactive oxygen species via photoexcitation of these photosensitizers in cancer cells. The fluorescence lifetimes of both photosensitizers in cancer cells are different from those in normal cells, which originates from the different intracellular environments around the photosensitizers between normal and cancer cells.", "classifications": [ { "id": "Nakabayashi", "label": "Group Nakabayashi", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Kamlesh", "last_name": "Awasthi", "name": null }, { "creator_type": "author", "first_name": "Kazuhito", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Kazunari", "last_name": "Furuya", "name": null }, { "creator_type": "author", "first_name": "Takakazu", "last_name": "Nakabayashi", "name": null }, { "creator_type": "author", "first_name": "Liming", "last_name": "Li", "name": null }, { "creator_type": "author", "first_name": "Nobuhiro", "last_name": "Ohta", "name": null } ], "identifiers": { "doi": { "normalized": "10.3390/s150511417" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "25993516" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Chlorophyll", "descriptor_ui": "D002734", "major_topic": false }, { "descriptor": "Photosensitizing Agents", "descriptor_ui": "D017319", "major_topic": false }, { "descriptor": "Porphyrins", "descriptor_ui": "D011166", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Spectrometry, Fluorescence", "descriptor_ui": "D013050", "major_topic": false } ], "publication": { "conference_name": null, "date": "2015 May", "date_precision": "unknown", "issue": "5", "normalized_date": null, "pages": "11417-11430", "proceedings_title": null, "publisher": "", "title": "Sensors (Basel, Switzerland)", "volume": "15", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "Fluorescence Characteristics and Lifetime Images of Photosensitizers of Talaporfin Sodium and Sodium Pheophorbide a in Normal and Cancer Cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The accumulation of uremic toxins is involved in the progression of CKD. Various uremic toxins are derived from gut microbiota, and an imbalance of gut microbiota or dysbiosis is related to renal failure. However, the pathophysiologic mechanisms underlying the relationship between the gut microbiota and renal failure are still obscure. Using an adenine-induced renal failure mouse model, we evaluated the effects of the ClC-2 chloride channel activator lubiprostone (commonly used for the treatment of constipation) on CKD. Oral administration of lubiprostone (500 microg/kg per day) changed the fecal and intestinal properties in mice with renal failure. Additionally, lubiprostone treatment reduced the elevated BUN and protected against tubulointerstitial damage, renal fibrosis, and inflammation. Gut microbiome analysis of 16S rRNA genes in the renal failure mice showed that lubiprostone treatment altered their microbial composition, especially the recovery of the levels of the Lactobacillaceae family and Prevotella genus, which were significantly reduced in the renal failure mice. Furthermore, capillary electrophoresis-mass spectrometry-based metabolome analysis showed that lubiprostone treatment decreased the plasma level of uremic toxins, such as indoxyl sulfate and hippurate, which are derived from gut microbiota, and a more recently discovered uremic toxin, trans-aconitate. These results suggest that lubiprostone ameliorates the progression of CKD and the accumulation of uremic toxins by improving the gut microbiota and intestinal environment.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Eikan", "last_name": "Mishima", "name": null }, { "creator_type": "author", "first_name": "Shinji", "last_name": "Fukuda", "name": null }, { "creator_type": "author", "first_name": "Hisato", "last_name": "Shima", "name": null }, { "creator_type": "author", "first_name": "Akiyoshi", "last_name": "Hirayama", "name": null }, { "creator_type": "author", "first_name": "Yasutoshi", "last_name": "Akiyama", "name": null }, { "creator_type": "author", "first_name": "Yoichi", "last_name": "Takeuchi", "name": null }, { "creator_type": "author", "first_name": "Noriko N.", "last_name": "Fukuda", "name": null }, { "creator_type": "author", "first_name": "Takehiro", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Chitose", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Akinori", "last_name": "Yuri", "name": null }, { "creator_type": "author", "first_name": "Koichi", "last_name": "Kikuchi", "name": null }, { "creator_type": "author", "first_name": "Yoshihisa", "last_name": "Tomioka", "name": null }, { "creator_type": "author", "first_name": "Sadayoshi", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Takaaki", "last_name": "Abe", "name": null } ], "identifiers": { "doi": { "normalized": "10.1681/asn.2014060530" }, "pmcid": { "normalized": "PMC4520171" }, "pmid": { "normalized": "25525179" } }, "mesh": [ { "descriptor": "Adenine", "descriptor_ui": "D000225", "major_topic": false }, { "descriptor": "Alprostadil", "descriptor_ui": "D000527", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Chloride Channel Agonists", "descriptor_ui": "D065101", "major_topic": false }, { "descriptor": "Disease Progression", "descriptor_ui": "D018450", "major_topic": false }, { "descriptor": "Drug Evaluation, Preclinical", "descriptor_ui": "D004353", "major_topic": false }, { "descriptor": "Gastrointestinal Tract", "descriptor_ui": "D041981", "major_topic": false }, { "descriptor": "Kidney Failure, Chronic", "descriptor_ui": "D007676", "major_topic": false }, { "descriptor": "Lubiprostone", "descriptor_ui": "D000068238", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Microbiota", "descriptor_ui": "D064307", "major_topic": false }, { "descriptor": "Random Allocation", "descriptor_ui": "D011897", "major_topic": false }, { "descriptor": "Uremia", "descriptor_ui": "D014511", "major_topic": false } ], "publication": { "conference_name": null, "date": "2015 Aug", "date_precision": "unknown", "issue": "8", "normalized_date": null, "pages": "1787-1794", "proceedings_title": null, "publisher": "", "title": "Journal of the American Society of Nephrology : JASN", "volume": "26", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "Alteration of the Intestinal Environment by Lubiprostone Is Associated with Amelioration of Adenine-Induced CKD.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Integrin-dependent cell-extracellular matrix (ECM) adhesion is a determinant of spindle orientation. However, the signaling pathways that couple integrins to spindle orientation remain elusive. Here, we show that PCTAIRE-1 kinase (PCTK1), a member of the cyclin-dependent kinases (CDKs) whose function is poorly characterized, plays an essential role in this process. PCTK1 regulates spindle orientation in a kinase-dependent manner. Phosphoproteomic analysis together with an RNA interference screen revealed that PCTK1 regulates spindle orientation through phosphorylation of Ser83 on KAP0, a regulatory subunit of protein kinase A (PKA). This phosphorylation is dispensable for KAP0 dimerization and for PKA binding but is necessary for its interaction with myosin X, a regulator of spindle orientation. KAP0 binds to the FERM domain of myosin X and enhances the association of myosin X-FERM with beta1 integrin. This interaction between myosin X-FERM and beta1 integrin appeared to be crucial for spindle orientation control. We propose that PCTK1-KAP0-myosin X-beta1 integrin is a functional module providing a link between ECM and the actin cytoskeleton in the ECM-dependent control of spindle orientation.", "classifications": [ { "id": "Toyoshima", "label": "Group Toyoshima", "parent": "Toyoshima", "type": "group" }, { "id": "Toyoshima", "label": "Team Toyoshima", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Sayaka", "last_name": "Iwano", "name": null }, { "creator_type": "author", "first_name": "Ayaka", "last_name": "Satou", "name": null }, { "creator_type": "author", "first_name": "Shigeru", "last_name": "Matsumura", "name": null }, { "creator_type": "author", "first_name": "Naoyuki", "last_name": "Sugiyama", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Ishihama", "name": null }, { "creator_type": "author", "first_name": "Fumiko", "last_name": "Toyoshima", "name": null } ], "identifiers": { "doi": { "normalized": "10.1128/mcb.01017-14" }, "pmcid": { "normalized": "PMC4355539" }, "pmid": { "normalized": "25605337" } }, "mesh": [ { "descriptor": "Cyclic AMP-Dependent Protein Kinases", "descriptor_ui": "D017868", "major_topic": false }, { "descriptor": "Cyclin-Dependent Kinases", "descriptor_ui": "D018844", "major_topic": false }, { "descriptor": "HeLa Cells", "descriptor_ui": "D006367", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Integrin beta1", "descriptor_ui": "D019012", "major_topic": false }, { "descriptor": "Myosins", "descriptor_ui": "D009218", "major_topic": false }, { "descriptor": "Protein Subunits", "descriptor_ui": "D021122", "major_topic": false }, { "descriptor": "Spindle Apparatus", "descriptor_ui": "D008941", "major_topic": false } ], "publication": { "conference_name": null, "date": "2015 Apr", "date_precision": "unknown", "issue": "7", "normalized_date": null, "pages": "1197-1208", "proceedings_title": null, "publisher": "", "title": "Molecular and cellular biology", "volume": "35", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "PCTK1 regulates integrin-dependent spindle orientation via protein kinase A regulatory subunit KAP0 and myosin X.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "We developed two types of artificial platforms, T-junction and crossroad microchannel devices, and obtained guidance response ratio of pollen tubes to the female tissue as 56-57%. The crossroad device was also able to collect the attracted pollen tubes with high purity, which is useful for future omics analysis.", "classifications": [ { "id": "Sato", "label": "Group Sato", "parent": "Tsuchiya", "type": "group" }, { "id": "Tsuchiya", "label": "Team Tsuchiya", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yoshikatsu", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Nagisa", "last_name": "Sugimoto", "name": null }, { "creator_type": "author", "first_name": "Tetsuya", "last_name": "Higashiyama", "name": null }, { "creator_type": "author", "first_name": "Hideyuki", "last_name": "Arata", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.jbiosc.2015.03.021" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "26116403" } }, "mesh": [ { "descriptor": "Dimethylpolysiloxanes", "descriptor_ui": "D004129", "major_topic": false }, { "descriptor": "Magnoliopsida", "descriptor_ui": "D019684", "major_topic": false }, { "descriptor": "Micro-Electrical-Mechanical Systems", "descriptor_ui": "D055617", "major_topic": false }, { "descriptor": "Microfluidic Analytical Techniques", "descriptor_ui": "D046210", "major_topic": true }, { "descriptor": "Ovule", "descriptor_ui": "D056771", "major_topic": false }, { "descriptor": "Pollen Tube", "descriptor_ui": "D053205", "major_topic": false } ], "publication": { "conference_name": null, "date": "2015 Dec", "date_precision": "unknown", "issue": "6", "normalized_date": null, "pages": "697-700", "proceedings_title": null, "publisher": "", "title": "Journal of bioscience and bioengineering", "volume": "120", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "Quantification of pollen tube attraction in response to guidance by female gametophyte tissue using artificial microscale pathway.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The piggyBac transposon was originally isolated from the cabbage looper moth, Trichoplusia ni, in the 1980s. Despite its early discovery and dissimilarity to the other DNA transposon families, the piggyBac transposon was not recognized as a member of a large transposon superfamily for a long time. Initially, the piggyBac transposon was thought to be a rare transposon. This view, however, has now been completely revised as a number of fully sequenced genomes have revealed the presence of piggyBac-like repetitive elements. The isolation of active copies of the piggyBac-like elements from several distinct species further supported this revision. This includes the first isolation of an active mammalian DNA transposon identified in the bat genome. To date, the piggyBac transposon has been deeply characterized and it represents a number of unique characteristics. In general, all members of the piggyBac superfamily use TTAA as their integration target sites. In addition, the piggyBac transposon shows precise excision, i.e., restoring the sequence to its preintegration state, and can transpose in a variety of organisms such as yeasts, malaria parasites, insects, mammals, and even in plants. Biochemical analysis of the chemical steps of transposition revealed that piggyBac does not require DNA synthesis during the actual transposition event. The broad host range has attracted researchers from many different fields, and the piggyBac transposon is currently the most widely used transposon system for genetic manipulations.", "classifications": [ { "id": "Yusa", "label": "Group Yusa", "parent": "Eiraku", "type": "group" }, { "id": "Eiraku", "label": "Team Eiraku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Kosuke", "last_name": "Yusa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1128/microbiolspec.mdna3-0028-2014" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "26104701" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "DNA", "descriptor_ui": "D004247", "major_topic": false }, { "descriptor": "DNA Transposable Elements", "descriptor_ui": "D004251", "major_topic": true }, { "descriptor": "Insecta", "descriptor_ui": "D007313", "major_topic": false }, { "descriptor": "Mammals", "descriptor_ui": "D008322", "major_topic": false }, { "descriptor": "Models, Biological", "descriptor_ui": "D008954", "major_topic": false }, { "descriptor": "Recombination, Genetic", "descriptor_ui": "D011995", "major_topic": false } ], "publication": { "conference_name": null, "date": "2015 Apr", "date_precision": "unknown", "issue": "2", "normalized_date": null, "pages": "MDNA3-0028-2014", "proceedings_title": null, "publisher": "", "title": "Microbiology spectrum", "volume": "3", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "piggyBac Transposon.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "OBJECTIVE: Extraovarian sex hormone production plays an important role in estrogen biosynthesis in postmenopausal women. We examined possible associations between serum sex hormone level and polymorphisms in CYP19A1, HSD17B1, and HSD17B2. We also assessed possible interaction between these polymorphisms and current overweight. METHODS: We conducted a cross-sectional study. 785 Japanese natural postmenopausal women were randomly selected from the Japan Multi-Institutional Collaborative Cohort (J-MICC) Study database. Information on lifestyle factors was obtained from a self-administered questionnaire. Serum estrogens and androgens levels were measured by liquid chromatography-tandem mass spectrometry. Four tag SNPs (single nucleotide polymorphisms) of CYP19A1, one missense SNP of HSD17B1 and three tag SNPs of HSD17B2 were examined by Invader assay. A trend test was conducted using linear regression. RESULTS: After adjustment for multiple comparisons, we found that rs4441215 and rs936306 in CYP19A1 and rs4888202 and rs2955160 in HSD17B2 were associated with differences in serum estrone level. Further, rs4441215 and rs936306 were associated with differences in serum estradiol level. None of these polymorphisms showed a significant interaction with current body mass index (BMI). CONCLUSIONS: Our findings suggested that CYP19A1 and HSD17B2 polymorphisms might be associated with circulating sex hormone levels in Japanese postmenopausal women, independent of current BMI.", "classifications": [ { "id": "Tanaka", "label": "Group Tanaka", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Satoyo", "last_name": "Hosono", "name": null }, { "creator_type": "author", "first_name": "Hidemi", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Isao", "last_name": "Oze", "name": null }, { "creator_type": "author", "first_name": "Yasuki", "last_name": "Higaki", "name": null }, { "creator_type": "author", "first_name": "Emi", "last_name": "Morita", "name": null }, { "creator_type": "author", "first_name": "Naoyuki", "last_name": "Takashima", "name": null }, { "creator_type": "author", "first_name": "Sadao", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Keiichi", "last_name": "Shimatani", "name": null }, { "creator_type": "author", "first_name": "Haruo", "last_name": "Mikami", "name": null }, { "creator_type": "author", "first_name": "Keizo", "last_name": "Ohnaka", "name": null }, { "creator_type": "author", "first_name": "Etsuko", "last_name": "Ozaki", "name": null }, { "creator_type": "author", "first_name": "Sakurako", "last_name": "Katsuura-Kamano", "name": null }, { "creator_type": "author", "first_name": "Michiaki", "last_name": "Kubo", "name": null }, { "creator_type": "author", "first_name": "Chisato", "last_name": "Nagata", "name": null }, { "creator_type": "author", "first_name": "Mariko", "last_name": "Naito", "name": null }, { "creator_type": "author", "first_name": "Nobuyuki", "last_name": "Hamajima", "name": null }, { "creator_type": "author", "first_name": "Hideo", "last_name": "Tanaka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.maturitas.2015.08.003" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "26323233" } }, "mesh": [ { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Aromatase", "descriptor_ui": "D001141", "major_topic": false }, { "descriptor": "Body Mass Index", "descriptor_ui": "D015992", "major_topic": false }, { "descriptor": "Cross-Sectional Studies", "descriptor_ui": "D003430", "major_topic": false }, { "descriptor": "Estradiol", "descriptor_ui": "D004958", "major_topic": false }, { "descriptor": "Estradiol Dehydrogenases", "descriptor_ui": "D004960", "major_topic": false }, { "descriptor": "Estrone", "descriptor_ui": "D004970", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Japan", "descriptor_ui": "D007564", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Overweight", "descriptor_ui": "D050177", "major_topic": false }, { "descriptor": "Polymorphism, Single Nucleotide", "descriptor_ui": "D020641", "major_topic": false }, { "descriptor": "Postmenopause", "descriptor_ui": "D017698", "major_topic": false } ], "publication": { "conference_name": null, "date": "2015 Dec", "date_precision": "unknown", "issue": "4", "normalized_date": null, "pages": "394-401", "proceedings_title": null, "publisher": "", "title": "Maturitas", "volume": "82", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "Polymorphisms in CYP19A1, HSD17B1 and HSD17B2 genes and serum sex hormone level among postmenopausal Japanese women.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The basic helix-loop-helix factors Hes1 and Hes5 repress the expression of proneural factors such as Ascl1, thereby inhibiting neuronal differentiation and maintaining neural progenitor cells (NPCs). Hes1 expression oscillates by negative feedback with a period of about 2-3 h in proliferating NPCs. Induction of sustained expression of Hes1 in NPCs inhibits their cell-cycle progression, suggesting that the oscillatory expression of Hes1 is important for the proliferation of NPCs. Hes1 oscillation drives the oscillatory expression of proneural factors such as Ascl1 by periodic repression. By contrast, in differentiating neurons, Hes1 expression disappears and the expression of proneural factors is up-regulated and sustained. A new optogenetics approach that induces Ascl1 expression by blue light illumination demonstrated that sustained expression of Ascl1 induces neuronal differentiation, whereas oscillatory expression of Ascl1 activates the proliferation of NPCs. These results together indicate that Hes1 regulates the oscillatory versus sustained expression of the proneural factor Ascl1, which in turn regulates the proliferation of NPCs and the subsequent processes of cell-cycle exit and neuronal fate determination, depending on the expression dynamics.", "classifications": [ { "id": "Imayoshi", "label": "Group Imayoshi", "parent": "Imayoshi", "type": "group" }, { "id": "Imayoshi", "label": "Team Imayoshi", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Ryoichiro", "last_name": "Kageyama", "name": null }, { "creator_type": "author", "first_name": "Hiromi", "last_name": "Shimojo", "name": null }, { "creator_type": "author", "first_name": "Itaru", "last_name": "Imayoshi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/s00441-014-1888-7" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "24850276" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Basic Helix-Loop-Helix Proteins", "descriptor_ui": "D051792", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Nervous System", "descriptor_ui": "D009420", "major_topic": false }, { "descriptor": "Neural Stem Cells", "descriptor_ui": "D058953", "major_topic": false }, { "descriptor": "Neurogenesis", "descriptor_ui": "D055495", "major_topic": true }, { "descriptor": "Optogenetics", "descriptor_ui": "D062308", "major_topic": false }, { "descriptor": "Receptors, Notch", "descriptor_ui": "D051880", "major_topic": false } ], "publication": { "conference_name": null, "date": "2015 Jan", "date_precision": "unknown", "issue": "1", "normalized_date": null, "pages": "125-133", "proceedings_title": null, "publisher": "", "title": "Cell and tissue research", "volume": "359", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "Dynamic expression and roles of Hes factors in neural development.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The CRISPR-Cas9 system consists of a site-specific, targetable DNA nuclease that holds great potential in gene editing and genome-wide screening applications. To apply the CRISPR-Cas9 system to these assays successfully, the rate at which Cas9 induces DNA breaks at undesired loci must be understood. We characterized the rate of Cas9 off-target activity in typical Cas9 experiments in two human and one mouse cell lines. We analyzed the Cas9 cutting activity of 12 gRNAs in both their targeted sites and approximately 90 predicted off-target sites per gRNA. In a Cas9-based knockout experiment, gRNAs induced detectable Cas9 cutting activity in all on-target sites and in only a few off-target sites genome-wide in human 293FT, human-induced pluripotent stem (hiPS) cells, and mouse embryonic stem (ES) cells. Both the cutting rates and DNA repair patterns were highly correlated between the two human cell lines in both on-target and off-target sites. In clonal Cas9 cutting analysis in mouse ES cells, biallelic Cas9 cutting was observed with low off-target activity. Our results show that off-target activity of Cas9 is low and predictable by the degree of sequence identity between the gRNA and a potential off-target site. Off-target Cas9 activity can be minimized by selecting gRNAs with few off-target sites of near complementarity.", "classifications": [ { "id": "Yusa", "label": "Group Yusa", "parent": "Eiraku", "type": "group" }, { "id": "Eiraku", "label": "Team Eiraku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "E.-Pien", "last_name": "Tan", "name": null }, { "creator_type": "author", "first_name": "Yilong", "last_name": "Li", "name": null }, { "creator_type": "author", "first_name": "Martin Del Castillo", "last_name": "Velasco-Herrera", "name": null }, { "creator_type": "author", "first_name": "Kosuke", "last_name": "Yusa", "name": null }, { "creator_type": "author", "first_name": "Allan", "last_name": "Bradley", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/dvg.22835" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "25378133" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Bacterial Proteins", "descriptor_ui": "D001426", "major_topic": false }, { "descriptor": "Base Sequence", "descriptor_ui": "D001483", "major_topic": false }, { "descriptor": "Clustered Regularly Interspaced Short Palindromic Repeats", "descriptor_ui": "D064112", "major_topic": false }, { "descriptor": "CRISPR-Associated Protein 9", "descriptor_ui": "D000076987", "major_topic": false }, { "descriptor": "DNA Cleavage", "descriptor_ui": "D053837", "major_topic": false }, { "descriptor": "DNA Repair", "descriptor_ui": "D004260", "major_topic": false }, { "descriptor": "Embryonic Stem Cells", "descriptor_ui": "D053595", "major_topic": false }, { "descriptor": "Endonucleases", "descriptor_ui": "D004720", "major_topic": false }, { "descriptor": "Gene Targeting", "descriptor_ui": "D018390", "major_topic": false }, { "descriptor": "Genetic Engineering", "descriptor_ui": "D005818", "major_topic": true }, { "descriptor": "HEK293 Cells", "descriptor_ui": "D057809", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Induced Pluripotent Stem Cells", "descriptor_ui": "D057026", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "RNA, Guide, CRISPR-Cas Systems", "descriptor_ui": "D000094704", "major_topic": false } ], "publication": { "conference_name": null, "date": "2015 Feb", "date_precision": "unknown", "issue": "2", "normalized_date": null, "pages": "225-236", "proceedings_title": null, "publisher": "", "title": "Genesis (New York, N.Y. : 2000)", "volume": "53", "year": 2015 }, "ssbd": { "database": [], "repository": [] }, "title": "Off-target assessment of CRISPR-Cas9 guiding RNAs in human iPS and mouse ES cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Aims: Liver injury and regeneration involve complicated processes and are affected by various physio-pathological factors. We investigated the mechanisms of steatosis-associated liver injury and delayed regeneration in a mouse model of partial hepatectomy. Results: Initial regeneration of the steatotic liver was significantly delayed after hepatectomy. Although hepatocyte proliferation was not significantly suppressed, severe liver injury with oxidative stress (OS) occurred immediately after hepatectomy in the steatotic liver. Fas-ligand (FasL)/Fas expression was upregulated in the steatotic liver, whereas the expression of antioxidant and anti-apoptotic molecules (catalase/MnSOD/Ref-1 and Bcl-2/Bcl-xL/FLIP, respectively) and p62/SQSTM1, a steatosis-associated protein, was downregulated. Interestingly, pro-survival Akt was not activated in response to hepatectomy, although it was sufficiently expressed even before hepatectomy. Suppression of p62/SQSTM1 increased FasL/Fas expression and reduced nuclear factor erythroid 2-related factor-2 (Nrf-2)-dependent antioxidant response elements activity and antioxidant responses in steatotic and nonsteatotic hepatocytes. Exogenously added FasL induced severe cellular OS and necrosis/apoptosis in steatotic hepatocytes, with only the necrosis being inhibited by pretreatment with antioxidants, suggesting that FasL/Fas-induced OS mainly leads to necrosis. Furthermore, p62/SQSTM1 re-expression in the steatotic liver markedly reduced liver injury and improved liver regeneration. Innovation: This study is the first which demonstrates that reduced expression of p62/SQSTM1 plays a crucial role in posthepatectomy acute injury and delayed regeneration of steatotic liver, mainly via redox-dependent mechanisms. Conclusion: In the steatotic liver, reduced expression of p62/SQSTM1 induced FasL/Fas overexpression and suppressed antioxidant genes, mainly through Nrf-2 inactivation, which, along with the hypo-responsiveness of Akt, caused posthepatectomy necrotic/apoptotic liver injury and delayed regeneration, both mainly via a redox-dependent mechanism. Antioxid. Redox Signal. 21, 2515–2530.", "classifications": [ { "id": "Inaba", "label": "Group Inaba", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Sanae", "last_name": "Haga", "name": null }, { "creator_type": "author", "first_name": "Takeaki", "last_name": "Ozawa", "name": null }, { "creator_type": "author", "first_name": "Yuma", "last_name": "Yamada", "name": null }, { "creator_type": "author", "first_name": "Naoki", "last_name": "Morita", "name": null }, { "creator_type": "author", "first_name": "Izuru", "last_name": "Nagashima", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Inoue", "name": null }, { "creator_type": "author", "first_name": "Yuka", "last_name": "Inaba", "name": null }, { "creator_type": "author", "first_name": "Natsumi", "last_name": "Noda", "name": null }, { "creator_type": "author", "first_name": "Riichiro", "last_name": "Abe", "name": null }, { "creator_type": "author", "first_name": "Kazuo", "last_name": "Umezawa", "name": null }, { "creator_type": "author", "first_name": "Michitaka", "last_name": "Ozaki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1089/ars.2013.5391" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "24925527" } }, "mesh": [ { "descriptor": "Adaptor Proteins, Signal Transducing", "descriptor_ui": "D048868", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Antioxidants", "descriptor_ui": "D000975", "major_topic": false }, { "descriptor": "Apoptosis", "descriptor_ui": "D017209", "major_topic": false }, { "descriptor": "Cell Proliferation", "descriptor_ui": "D049109", "major_topic": false }, { "descriptor": "Disease Models, Animal", "descriptor_ui": "D004195", "major_topic": false }, { "descriptor": "Fas Ligand Protein", "descriptor_ui": "D053222", "major_topic": false }, { "descriptor": "Fatty Liver", "descriptor_ui": "D005234", "major_topic": false }, { "descriptor": "Heat-Shock Proteins", "descriptor_ui": "D006360", "major_topic": false }, { "descriptor": "Hepatectomy", "descriptor_ui": "D006498", "major_topic": false }, { "descriptor": "Hepatocytes", "descriptor_ui": "D022781", "major_topic": false }, { "descriptor": "Liver Regeneration", "descriptor_ui": "D008115", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "NF-E2-Related Factor 2", "descriptor_ui": "D051267", "major_topic": false }, { "descriptor": "Oxidation-Reduction", "descriptor_ui": "D010084", "major_topic": false }, { "descriptor": "Oxidative Stress", "descriptor_ui": "D018384", "major_topic": true }, { "descriptor": "Sequestosome-1 Protein", "descriptor_ui": "D000071456", "major_topic": false } ], "publication": { "conference_name": null, "date": "2014 Dec 20", "date_precision": "day", "issue": "18", "normalized_date": "2014-12-20", "pages": "2515-2530", "proceedings_title": null, "publisher": "", "title": "Antioxidants & Redox Signaling", "volume": "21", "year": 2014 }, "ssbd": { "database": [], "repository": [] }, "title": "p62/SQSTM1 Plays a Protective Role in Oxidative Injury of Steatotic Liver in a Mouse Hepatectomy Model.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Cell division is controlled by a multitude of protein enzymes, but little is known about roles of metabolites in this mechanism. Here, we show that pregnenolone (P5), a steroid that is produced from cholesterol by the steroidogenic enzyme Cyp11a1, has an essential role in centriole cohesion during mitosis. During prometa-metaphase, P5 is accumulated around the spindle poles. Depletion of P5 induces multipolar spindles that result from premature centriole disengagement, which are rescued by ectopic introduction of P5, but not its downstream metabolites, into the cells. Premature centriole disengagement, induced by loss of P5, is not a result of precocious activation of separase, a key factor for the centriole disengagement in anaphase. Rather, P5 directly binds to the N-terminal coiled-coil domain of short-form of shugoshin 1 (sSgo1), a protector for centriole cohesion and recruits it to spindle poles in mitosis. Our results thus reveal a steroid-mediated centriole protection mechanism.", "classifications": [ { "id": "Toyoshima", "label": "Group Toyoshima", "parent": "Toyoshima", "type": "group" }, { "id": "Toyoshima", "label": "Team Toyoshima", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Mayumi", "last_name": "Hamasaki", "name": null }, { "creator_type": "author", "first_name": "Shigeru", "last_name": "Matsumura", "name": null }, { "creator_type": "author", "first_name": "Ayaka", "last_name": "Satou", "name": null }, { "creator_type": "author", "first_name": "Chisato", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Yukako", "last_name": "Oda", "name": null }, { "creator_type": "author", "first_name": "Chika", "last_name": "Higashiura", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Ishihama", "name": null }, { "creator_type": "author", "first_name": "Fumiko", "last_name": "Toyoshima", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.chembiol.2014.11.005" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "25525990" } }, "mesh": [ { "descriptor": "Cell Cycle Proteins", "descriptor_ui": "D018797", "major_topic": false }, { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "Centrioles", "descriptor_ui": "D002502", "major_topic": false }, { "descriptor": "Cholesterol Side-Chain Cleavage Enzyme", "descriptor_ui": "D002786", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mitosis", "descriptor_ui": "D008938", "major_topic": true }, { "descriptor": "Phosphorylation", "descriptor_ui": "D010766", "major_topic": false }, { "descriptor": "Polo-Like Kinase 1", "descriptor_ui": "D000097869", "major_topic": false }, { "descriptor": "Pregnenolone", "descriptor_ui": "D011284", "major_topic": false }, { "descriptor": "Protein Kinase Inhibitors", "descriptor_ui": "D047428", "major_topic": false }, { "descriptor": "Protein Serine-Threonine Kinases", "descriptor_ui": "D017346", "major_topic": false }, { "descriptor": "Protein Transport", "descriptor_ui": "D021381", "major_topic": false }, { "descriptor": "Proto-Oncogene Proteins", "descriptor_ui": "D011518", "major_topic": false } ], "publication": { "conference_name": null, "date": "2014 Dec 18", "date_precision": "day", "issue": "12", "normalized_date": "2014-12-18", "pages": "1707-1721", "proceedings_title": null, "publisher": "", "title": "Chemistry & biology", "volume": "21", "year": 2014 }, "ssbd": { "database": [], "repository": [] }, "title": "Pregnenolone functions in centriole cohesion during mitosis.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "", "classifications": [ { "id": "Akaike", "label": "Group Akaike", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Hatsumi", "last_name": "Okubo", "name": null }, { "creator_type": "author", "first_name": "Masahide", "last_name": "Goto", "name": null }, { "creator_type": "author", "first_name": "Miori", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Teruyuki", "last_name": "Sugiyama", "name": null }, { "creator_type": "author", "first_name": "Mikihiko", "last_name": "Kawano", "name": null }, { "creator_type": "author", "first_name": "Tetsuro", "last_name": "Matsunaga", "name": null }, { "creator_type": "author", "first_name": "Takaaki", "last_name": "Akaike", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.jns.2014.10.011" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "25394907" } }, "mesh": [ { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Bacteremia", "descriptor_ui": "D016470", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Helicobacter", "descriptor_ui": "D016998", "major_topic": false }, { "descriptor": "Helicobacter Infections", "descriptor_ui": "D016481", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Infant, Newborn", "descriptor_ui": "D007231", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Meningitis, Bacterial", "descriptor_ui": "D016920", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Polymerase Chain Reaction", "descriptor_ui": "D016133", "major_topic": false } ], "publication": { "conference_name": null, "date": "2014 Dec 15", "date_precision": "day", "issue": "1-2", "normalized_date": "2014-12-15", "pages": "396-397", "proceedings_title": null, "publisher": "", "title": "Journal of the neurological sciences", "volume": "347", "year": 2014 }, "ssbd": { "database": [], "repository": [] }, "title": "Helicobacter cinaedi meningitis: a case report and review of previous cases.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Genome-wide association studies (GWAS) have mapped risk alleles for at least 10 distinct cancers to a small region of 63 000 bp on chromosome 5p15.33. This region harbors the TERT and CLPTM1L genes; the former encodes the catalytic subunit of telomerase reverse transcriptase and the latter may play a role in apoptosis. To investigate further the genetic architecture of common susceptibility alleles in this region, we conducted an agnostic subset-based meta-analysis (association analysis based on subsets) across six distinct cancers in 34 248 cases and 45 036 controls. Based on sequential conditional analysis, we identified as many as six independent risk loci marked by common single-nucleotide polymorphisms: five in the TERT gene (Region 1: rs7726159, P = 2.10 x 10(-39); Region 3: rs2853677, P = 3.30 x 10(-36) and PConditional = 2.36 x 10(-8); Region 4: rs2736098, P = 3.87 x 10(-12) and PConditional = 5.19 x 10(-6), Region 5: rs13172201, P = 0.041 and PConditional = 2.04 x 10(-6); and Region 6: rs10069690, P = 7.49 x 10(-15) and PConditional = 5.35 x 10(-7)) and one in the neighboring CLPTM1L gene (Region 2: rs451360; P = 1.90 x 10(-18) and PConditional = 7.06 x 10(-16)). Between three and five cancers mapped to each independent locus with both risk-enhancing and protective effects. Allele-specific effects on DNA methylation were seen for a subset of risk loci, indicating that methylation and subsequent effects on gene expression may contribute to the biology of risk variants on 5p15.33. Our results provide strong support for extensive pleiotropy across this region of 5p15.33, to an extent not previously observed in other cancer susceptibility loci.", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Zhaoming", "last_name": "Wang", "name": null }, { "creator_type": "author", "first_name": "Bin", "last_name": "Zhu", "name": null }, { "creator_type": "author", "first_name": "Mingfeng", "last_name": "Zhang", "name": null }, { "creator_type": "author", "first_name": "Hemang", "last_name": "Parikh", "name": null }, { "creator_type": "author", "first_name": "Jinping", "last_name": "Jia", "name": null }, { "creator_type": "author", "first_name": "Charles C.", "last_name": "Chung", "name": null }, { "creator_type": "author", "first_name": "Joshua N.", "last_name": "Sampson", "name": null }, { "creator_type": "author", "first_name": "Jason W.", "last_name": "Hoskins", "name": null }, { "creator_type": "author", "first_name": "Amy", "last_name": "Hutchinson", "name": null }, { "creator_type": "author", "first_name": "Laurie", "last_name": "Burdette", "name": null }, { "creator_type": "author", "first_name": "Abdisamad", "last_name": "Ibrahim", "name": null }, { "creator_type": "author", "first_name": "Christopher", "last_name": "Hautman", "name": null }, { "creator_type": "author", "first_name": "Preethi S.", "last_name": "Raj", "name": null }, { "creator_type": "author", "first_name": "Christian C.", "last_name": "Abnet", "name": null }, { "creator_type": "author", "first_name": "Andrew A.", "last_name": "Adjei", "name": null }, { "creator_type": "author", "first_name": "Anders", "last_name": "Ahlbom", "name": null }, { "creator_type": "author", "first_name": "Demetrius", "last_name": "Albanes", "name": null }, { "creator_type": "author", "first_name": "Naomi E.", "last_name": "Allen", "name": null }, { "creator_type": "author", "first_name": "Christine B.", "last_name": "Ambrosone", "name": null }, { "creator_type": "author", "first_name": "Melinda", "last_name": "Aldrich", "name": null }, { "creator_type": "author", "first_name": "Pilar", "last_name": "Amiano", "name": null }, { "creator_type": "author", "first_name": "Christopher", "last_name": "Amos", "name": null }, { "creator_type": "author", "first_name": "Ulrika", "last_name": "Andersson", "name": null }, { "creator_type": "author", "first_name": "Gerald Jr", "last_name": "Andriole", "name": null }, { "creator_type": "author", "first_name": "Irene L.", "last_name": "Andrulis", "name": null }, { "creator_type": "author", "first_name": "Cecilia", "last_name": "Arici", "name": null }, { "creator_type": "author", "first_name": "Alan A.", "last_name": "Arslan", "name": null }, { "creator_type": "author", "first_name": "Melissa A.", "last_name": "Austin", "name": null }, { "creator_type": "author", "first_name": "Dalsu", "last_name": "Baris", "name": null }, { "creator_type": "author", "first_name": "Donald A.", "last_name": "Barkauskas", "name": null }, { "creator_type": "author", "first_name": "Bryan A.", "last_name": "Bassig", "name": null }, { "creator_type": "author", "first_name": "Laura E.", "last_name": "Beane Freeman", "name": null }, { "creator_type": "author", "first_name": "Christine D.", "last_name": "Berg", "name": null }, { "creator_type": "author", "first_name": "Sonja I.", "last_name": "Berndt", "name": null }, { "creator_type": "author", "first_name": "Pier Alberto", "last_name": "Bertazzi", "name": null }, { "creator_type": "author", "first_name": "Richard B.", "last_name": "Biritwum", "name": null }, { "creator_type": "author", "first_name": "Amanda", "last_name": "Black", "name": null }, { "creator_type": "author", "first_name": "William", "last_name": "Blot", "name": null }, { "creator_type": "author", "first_name": "Heiner", "last_name": "Boeing", "name": null }, { "creator_type": "author", "first_name": "Paolo", "last_name": "Boffetta", "name": null }, { "creator_type": "author", "first_name": "Kelly", "last_name": "Bolton", "name": null }, { "creator_type": "author", "first_name": "Marie-Christine", "last_name": "Boutron-Ruault", "name": null }, { "creator_type": "author", "first_name": "Paige M.", "last_name": "Bracci", "name": null }, { "creator_type": "author", "first_name": "Paul", "last_name": "Brennan", "name": null }, { "creator_type": "author", "first_name": "Louise A.", "last_name": "Brinton", "name": null }, { "creator_type": "author", "first_name": "Michelle", "last_name": "Brotzman", "name": null }, { "creator_type": "author", "first_name": "H. Bas", "last_name": "Bueno-de-Mesquita", "name": null }, { "creator_type": "author", "first_name": "Julie E.", "last_name": "Buring", "name": null }, { "creator_type": "author", "first_name": "Mary Ann", "last_name": "Butler", "name": null }, { "creator_type": "author", "first_name": "Qiuyin", "last_name": "Cai", "name": null }, { "creator_type": "author", "first_name": "Geraldine", "last_name": "Cancel-Tassin", "name": null }, { "creator_type": "author", "first_name": "Federico", "last_name": "Canzian", "name": null }, { "creator_type": "author", "first_name": "Guangwen", "last_name": "Cao", "name": null }, { "creator_type": "author", "first_name": "Neil E.", "last_name": "Caporaso", "name": null }, { "creator_type": "author", "first_name": "Alfredo", "last_name": "Carrato", "name": null }, { "creator_type": "author", "first_name": "Tania", "last_name": "Carreon", "name": null }, { "creator_type": "author", "first_name": "Angela", "last_name": "Carta", "name": null }, { "creator_type": "author", "first_name": "Gee-Chen", "last_name": "Chang", "name": null }, { "creator_type": "author", "first_name": "I.-Shou", "last_name": "Chang", "name": null }, { "creator_type": "author", "first_name": "Jenny", "last_name": "Chang-Claude", "name": null }, { "creator_type": "author", "first_name": "Xu", "last_name": "Che", "name": null }, { "creator_type": "author", "first_name": "Chien-Jen", "last_name": "Chen", "name": null }, { "creator_type": "author", "first_name": "Chih-Yi", "last_name": "Chen", "name": null }, { "creator_type": "author", "first_name": "Chung-Hsing", "last_name": "Chen", "name": null }, { "creator_type": "author", "first_name": "Constance", "last_name": "Chen", "name": null }, { "creator_type": "author", "first_name": "Kuan-Yu", "last_name": "Chen", "name": null }, { "creator_type": "author", "first_name": "Yuh-Min", "last_name": "Chen", "name": null }, { "creator_type": "author", "first_name": "Anand P.", "last_name": "Chokkalingam", "name": null }, { "creator_type": "author", "first_name": "Lisa W.", "last_name": "Chu", "name": null }, { "creator_type": "author", "first_name": "Francoise", "last_name": "Clavel-Chapelon", "name": null }, { "creator_type": "author", "first_name": "Graham A.", "last_name": "Colditz", "name": null }, { "creator_type": "author", "first_name": "Joanne S.", "last_name": "Colt", "name": null }, { "creator_type": "author", "first_name": "David", "last_name": "Conti", "name": null }, { "creator_type": "author", "first_name": "Michael B.", "last_name": "Cook", "name": null }, { "creator_type": "author", "first_name": "Victoria K.", "last_name": "Cortessis", "name": null }, { "creator_type": "author", "first_name": "E. David", "last_name": "Crawford", "name": null }, { "creator_type": "author", "first_name": "Olivier", "last_name": "Cussenot", "name": null }, { "creator_type": "author", "first_name": "Faith G.", "last_name": "Davis", "name": null }, { "creator_type": "author", "first_name": "Immaculata", "last_name": "De Vivo", "name": null }, { "creator_type": "author", "first_name": "Xiang", "last_name": "Deng", "name": null }, { "creator_type": "author", "first_name": "Ti", "last_name": "Ding", "name": null }, { "creator_type": "author", "first_name": "Colin P.", "last_name": "Dinney", "name": null }, { "creator_type": "author", "first_name": "Anna Luisa", "last_name": "Di Stefano", "name": null }, { "creator_type": "author", "first_name": "W. Ryan", "last_name": "Diver", "name": null }, { "creator_type": "author", "first_name": "Eric J.", "last_name": "Duell", "name": null }, { "creator_type": "author", "first_name": "Joanne W.", "last_name": "Elena", "name": null }, { "creator_type": "author", "first_name": "Jin-Hu", "last_name": "Fan", "name": null }, { "creator_type": "author", "first_name": "Heather Spencer", "last_name": "Feigelson", "name": null }, { "creator_type": "author", "first_name": "Maria", "last_name": "Feychting", "name": null }, { "creator_type": "author", "first_name": "Jonine D.", "last_name": "Figueroa", "name": null }, { "creator_type": "author", "first_name": "Adrienne M.", "last_name": "Flanagan", "name": null }, { "creator_type": "author", "first_name": "Joseph F. 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"last_name": "Wu", "name": null }, { "creator_type": "author", "first_name": "Yi-Long", "last_name": "Wu", "name": null }, { "creator_type": "author", "first_name": "Jay S.", "last_name": "Wunder", "name": null }, { "creator_type": "author", "first_name": "Yong-Bing", "last_name": "Xiang", "name": null }, { "creator_type": "author", "first_name": "Jun", "last_name": "Xu", "name": null }, { "creator_type": "author", "first_name": "Hannah P.", "last_name": "Yang", "name": null }, { "creator_type": "author", "first_name": "Pan-Chyr", "last_name": "Yang", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null }, { "creator_type": "author", "first_name": "Yuanqing", "last_name": "Ye", "name": null }, { "creator_type": "author", "first_name": "Edward D.", "last_name": "Yeboah", "name": null }, { "creator_type": "author", "first_name": "Zhihua", "last_name": "Yin", "name": null }, { "creator_type": "author", "first_name": "Chen", "last_name": "Ying", "name": null }, { "creator_type": "author", "first_name": "Chong-Jen", "last_name": "Yu", "name": null }, { "creator_type": "author", "first_name": "Kai", "last_name": "Yu", "name": null }, { "creator_type": "author", "first_name": "Jian-Min", "last_name": "Yuan", "name": null }, { "creator_type": "author", "first_name": "Krista A.", "last_name": "Zanetti", "name": null }, { "creator_type": "author", "first_name": "Anne", "last_name": "Zeleniuch-Jacquotte", "name": null }, { "creator_type": "author", "first_name": "Wei", "last_name": "Zheng", "name": null }, { "creator_type": "author", "first_name": "Baosen", "last_name": "Zhou", "name": null }, { "creator_type": "author", "first_name": "Lisa", "last_name": "Mirabello", "name": null }, { "creator_type": "author", "first_name": "Sharon A.", "last_name": "Savage", "name": null }, { "creator_type": "author", "first_name": "Peter", "last_name": "Kraft", "name": null }, { "creator_type": "author", "first_name": "Stephen J.", "last_name": "Chanock", "name": null }, { "creator_type": "author", "first_name": "Meredith", "last_name": "Yeager", "name": null }, { "creator_type": "author", "first_name": "Maria Terese", "last_name": "Landi", "name": null }, { "creator_type": "author", "first_name": "Jianxin", "last_name": "Shi", "name": null }, { "creator_type": "author", "first_name": "Nilanjan", "last_name": "Chatterjee", "name": null }, { "creator_type": "author", "first_name": "Laufey T.", "last_name": "Amundadottir", "name": null } ], "identifiers": { "doi": { "normalized": "10.1093/hmg/ddu363" }, "pmcid": { "normalized": "PMC4240198" }, "pmid": { "normalized": "25027329" } }, "mesh": [ { "descriptor": "Alleles", "descriptor_ui": "D000483", "major_topic": false }, { "descriptor": "Chromosomes, Human, Pair 5", "descriptor_ui": "D002895", "major_topic": false }, { "descriptor": "Computational Biology", "descriptor_ui": "D019295", "major_topic": false }, { "descriptor": "DNA Methylation", "descriptor_ui": "D019175", "major_topic": false }, { "descriptor": "Epigenesis, Genetic", "descriptor_ui": "D044127", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Gene Expression Regulation, Neoplastic", "descriptor_ui": "D015972", "major_topic": true }, { "descriptor": "Gene Frequency", "descriptor_ui": "D005787", "major_topic": false }, { "descriptor": "Genetic Loci", "descriptor_ui": "D056426", "major_topic": true }, { "descriptor": "Genetic Predisposition to Disease", "descriptor_ui": "D020022", "major_topic": false }, { "descriptor": "Genome-Wide Association Study", "descriptor_ui": "D055106", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Membrane Proteins", "descriptor_ui": "D008565", "major_topic": false }, { "descriptor": "Neoplasm Proteins", "descriptor_ui": "D009363", "major_topic": false }, { "descriptor": "Neoplasms", "descriptor_ui": "D009369", "major_topic": false }, { "descriptor": "Odds Ratio", "descriptor_ui": "D016017", "major_topic": false }, { "descriptor": "Polymorphism, Single Nucleotide", "descriptor_ui": "D020641", "major_topic": false }, { "descriptor": "Risk", "descriptor_ui": "D012306", "major_topic": false }, { "descriptor": "Telomerase", "descriptor_ui": "D019098", "major_topic": false } ], "publication": { "conference_name": null, "date": "2014 Dec 15", "date_precision": "day", "issue": "24", "normalized_date": "2014-12-15", "pages": "6616-6633", "proceedings_title": null, "publisher": "", "title": "Human molecular genetics", "volume": "23", "year": 2014 }, "ssbd": { "database": [], "repository": [] }, "title": "Imputation and subset-based association analysis across different cancer types identifies multiple independent risk loci in the TERT-CLPTM1L region on chromosome 5p15.33.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Neocortical neurons with similar functional properties assemble into spatially coherent circuits, but it remains unclear how inhibitory interneurons are organized. We applied in vivo two-photon functional Ca(2+) imaging and whole-cell recording of synaptic currents to record visual responses of cortical neurons and analyzed their spatial arrangements. GABAergic interneurons were clustered in the 3D space of the mouse visual cortex, and excitatory neurons located within the clusters (insiders) had a lower amplitude and sharper orientation tuning of visual responses than outsiders. Inhibitory synaptic currents recorded from the insiders were larger than those of the outsiders. Single, isolated interneurons did not show such a location-tuning/amplitude relationship. The two principal subtypes of interneurons, parvalbumin- and somatostatin-expressing neurons, also formed clusters with only slightly overlapping each other and exhibited a different location-tuning relationship. These findings suggest that GABAergic interneurons and their subgroups form clusters to make their inhibitory function more effective than isolated interneurons.", "classifications": [ { "id": "Imayoshi", "label": "Group Imayoshi", "parent": "Imayoshi", "type": "group" }, { "id": "Imayoshi", "label": "Team Imayoshi", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Teppei", "last_name": "Ebina", "name": null }, { "creator_type": "author", "first_name": "Kazuhiro", "last_name": "Sohya", "name": null }, { "creator_type": "author", "first_name": "Itaru", "last_name": "Imayoshi", "name": null }, { "creator_type": "author", "first_name": "Shu-Ting", "last_name": "Yin", "name": null }, { "creator_type": "author", "first_name": "Rui", "last_name": "Kimura", "name": null }, { "creator_type": "author", "first_name": "Yuchio", "last_name": "Yanagawa", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Kameda", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Hioki", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Kaneko", "name": null }, { "creator_type": "author", "first_name": "Tadaharu", "last_name": "Tsumoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.celrep.2014.10.057" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "25464846" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Calcium Signaling", "descriptor_ui": "D020013", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "GABAergic Neurons", "descriptor_ui": "D059330", "major_topic": false }, { "descriptor": "Imaging, Three-Dimensional", "descriptor_ui": "D021621", "major_topic": false }, { "descriptor": "Interneurons", "descriptor_ui": "D007395", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Membrane Potentials", "descriptor_ui": "D008564", "major_topic": false }, { "descriptor": "Mice, Transgenic", "descriptor_ui": "D008822", "major_topic": false }, { "descriptor": "Photic Stimulation", "descriptor_ui": "D010775", "major_topic": false }, { "descriptor": "Visual Cortex", "descriptor_ui": "D014793", "major_topic": false }, { "descriptor": "Visual Perception", "descriptor_ui": "D014796", "major_topic": false } ], "publication": { "conference_name": null, "date": "2014 Dec 11", "date_precision": "day", "issue": "5", "normalized_date": "2014-12-11", "pages": "1896-1907", "proceedings_title": null, "publisher": "", "title": "Cell reports", "volume": "9", "year": 2014 }, "ssbd": { "database": [], "repository": [] }, "title": "3D clustering of GABAergic neurons enhances inhibitory actions on excitatory neurons in the mouse visual cortex.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The reprogramming of differentiated cells into induced pluripotent stem cells (iPSCs) can be achieved by ectopic expression of defined transcription factors (Oct3/4, Sox2, Klf4 and c-Myc). However, to date, some iPSCs have been generated using viral vectors; thus, unexpected insertional mutagenesis in the target cells would be a potential risk. Here we report reprogramming of siPSCs (gene silencing-induced pluripotent stem cells) from mouse neonatal cardiomyocytes (CMs) by combining TGF-beta signal inhibition and connexin43 (Cx43) silencing, and show that siPSCs show pluripotency in vitro and in vivo. Our novel non-insertional mutagenesis technique may provide a means for iPSC generation.", "classifications": [ { "id": "Tanaka", "label": "Group Tanaka", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Ping", "last_name": "Dai", "name": null }, { "creator_type": "author", "first_name": "Yoshinori", "last_name": "Harada", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Miyachi", "name": null }, { "creator_type": "author", "first_name": "Hideo", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Satsuki", "last_name": "Kitano", "name": null }, { "creator_type": "author", "first_name": "Tetsuya", "last_name": "Adachi", "name": null }, { "creator_type": "author", "first_name": "Tomoyuki", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Hino", "name": null }, { "creator_type": "author", "first_name": "Tetsuro", "last_name": "Takamatsu", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/srep07323" }, "pmcid": { "normalized": "PMC4255192" }, "pmid": { "normalized": "25471520" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Cellular Reprogramming", "descriptor_ui": "D065150", "major_topic": false }, { "descriptor": "Connexin 43", "descriptor_ui": "D018031", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Gene Silencing", "descriptor_ui": "D020868", "major_topic": false }, { "descriptor": "Genetic Vectors", "descriptor_ui": "D005822", "major_topic": false }, { "descriptor": "Induced Pluripotent Stem Cells", "descriptor_ui": "D057026", "major_topic": false }, { "descriptor": "Kruppel-Like Factor 4", "descriptor_ui": "D000090062", "major_topic": false }, { "descriptor": "Kruppel-Like Transcription Factors", "descriptor_ui": "D051741", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Inbred ICR", "descriptor_ui": "D008813", "major_topic": false }, { "descriptor": "Myocytes, Cardiac", "descriptor_ui": "D032383", "major_topic": false }, { "descriptor": "Octamer Transcription Factor-3", "descriptor_ui": "D050814", "major_topic": false }, { "descriptor": "Proto-Oncogene Proteins c-myc", "descriptor_ui": "D016271", "major_topic": false }, { "descriptor": "SOXB1 Transcription Factors", "descriptor_ui": "D055748", "major_topic": false }, { "descriptor": "Transcription Factors", "descriptor_ui": "D014157", "major_topic": false }, { "descriptor": "Transforming Growth Factor beta", "descriptor_ui": "D016212", "major_topic": false } ], "publication": { "conference_name": null, "date": "2014 Dec 4", "date_precision": "day", "issue": "", "normalized_date": "2014-12-04", "pages": "7323", "proceedings_title": null, "publisher": "", "title": "Scientific reports", "volume": "4", "year": 2014 }, "ssbd": { "database": [], "repository": [] }, "title": "Combining TGF-beta signal inhibition and connexin43 silencing for iPSC induction from mouse cardiomyocytes.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Serum gamma-glutamyl di- and tripeptides have proven to be useful biomarkers to accurately predict nine different forms of liver disease. Using liquid chromatography-tandem mass spectrometry (LC-MS/MS) with multiple reaction monitoring (MRM), serum and liver samples spiked with gamma-glutamyl peptide standards were analyzed to estimate accuracy. Unexpectedly, the recovery rates for several gamma-glutamyl peptides in the serum samples were quite low, whereas values for some gamma-glutamyl peptides in the liver samples were highly elevated. Most of these peptides were barely retained on the reverse-phase column, resulting in significant ion suppression or enhancement. In contrast, a capillary electrophoresis tandem mass spectrometry (CE-MS/MS) method with MRM was minimally affected by matrix effects. Of the 39 tested compounds, most of gamma-glutamyl peptides that did not contain a thiol substituent in its structure gave acceptable recoveries (70-120%), and limits of detection for the analytes were between 3.6 and 800 nmol/l with pressure injection at 5 kPa for 10 s (ca. 10 nl). The CE-MS/MS method provided high resolution and proved to be highly selective and sensitive, its utility being demonstrated by the determination of gamma-glutamyl di- and tripeptides in serum and liver samples.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Akiyoshi", "last_name": "Hirayama", "name": null }, { "creator_type": "author", "first_name": "Kaori", "last_name": "Igarashi", "name": null }, { "creator_type": "author", "first_name": "Masaru", "last_name": "Tomita", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.chroma.2014.10.007" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "25441083" } }, "mesh": [ { "descriptor": "Chromatography, Liquid", "descriptor_ui": "D002853", "major_topic": false }, { "descriptor": "Electrophoresis, Capillary", "descriptor_ui": "D019075", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Hydrogen-Ion Concentration", "descriptor_ui": "D006863", "major_topic": false }, { "descriptor": "Liver", "descriptor_ui": "D008099", "major_topic": false }, { "descriptor": "Peptides", "descriptor_ui": "D010455", "major_topic": false }, { "descriptor": "Reproducibility of Results", "descriptor_ui": "D015203", "major_topic": false }, { "descriptor": "Tandem Mass Spectrometry", "descriptor_ui": "D053719", "major_topic": false } ], "publication": { "conference_name": null, "date": "2014 Nov 21", "date_precision": "day", "issue": "", "normalized_date": "2014-11-21", "pages": "161-169", "proceedings_title": null, "publisher": "", "title": "Journal of chromatography. A", "volume": "1369", "year": 2014 }, "ssbd": { "database": [], "repository": [] }, "title": "Development of quantitative method for determination of gamma-glutamyl peptides by capillary electrophoresis tandem mass spectrometry: an efficient approach avoiding matrix effect.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Genome engineering using programmable nucleases enables homologous recombination (HR)-mediated gene knock-in. However, the labour used to construct targeting vectors containing homology arms and difficulties in inducing HR in some cell type and organisms represent technical hurdles for the application of HR-mediated knock-in technology. Here, we introduce an alternative strategy for gene knock-in using transcription activator-like effector nucleases (TALENs) and clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated 9 (Cas9) mediated by microhomology-mediated end-joining, termed the PITCh (Precise Integration into Target Chromosome) system. TALEN-mediated PITCh, termed TAL-PITCh, enables efficient integration of exogenous donor DNA in human cells and animals, including silkworms and frogs. We further demonstrate that CRISPR/Cas9-mediated PITCh, termed CRIS-PITCh, can be applied in human cells without carrying the plasmid backbone sequence. Thus, our PITCh-ing strategies will be useful for a variety of applications, not only in cultured cells, but also in various organisms, including invertebrates and vertebrates.", "classifications": [ { "id": "Suzuki", "label": "Group Suzuki", "parent": "Morishita", "type": "group" }, { "id": "Morishita", "label": "Team Morishita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Shota", "last_name": "Nakade", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Tsubota", "name": null }, { "creator_type": "author", "first_name": "Yuto", "last_name": "Sakane", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Kume", "name": null }, { "creator_type": "author", "first_name": "Naoaki", "last_name": "Sakamoto", "name": null }, { "creator_type": "author", "first_name": "Masanobu", "last_name": "Obara", "name": null }, { "creator_type": "author", "first_name": "Takaaki", "last_name": "Daimon", "name": null }, { "creator_type": "author", "first_name": "Hideki", "last_name": "Sezutsu", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Tetsushi", "last_name": "Sakuma", "name": null }, { "creator_type": "author", "first_name": "Ken-ichi T.", "last_name": "Suzuki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/ncomms6560" }, "pmcid": { "normalized": "PMC4263139" }, "pmid": { "normalized": "25410609" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Base Sequence", "descriptor_ui": "D001483", "major_topic": false }, { "descriptor": "Bombyx", "descriptor_ui": "D012831", "major_topic": false }, { "descriptor": "CRISPR-Cas Systems", "descriptor_ui": "D064113", "major_topic": true }, { "descriptor": "Deoxyribonucleases", "descriptor_ui": "D003851", "major_topic": true }, { "descriptor": "DNA", "descriptor_ui": "D004247", "major_topic": false }, { "descriptor": "Gene Knock-In Techniques", "descriptor_ui": "D055879", "major_topic": false }, { "descriptor": "Genetic Engineering", "descriptor_ui": "D005818", "major_topic": false }, { "descriptor": "Genetic Vectors", "descriptor_ui": "D005822", "major_topic": false }, { "descriptor": "Homologous Recombination", "descriptor_ui": "D059765", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Molecular Sequence Data", "descriptor_ui": "D008969", "major_topic": false }, { "descriptor": "Plasmids", "descriptor_ui": "D010957", "major_topic": false }, { "descriptor": "Saccharomyces cerevisiae", "descriptor_ui": "D012441", "major_topic": false }, { "descriptor": "Xenopus", "descriptor_ui": "D014981", "major_topic": false } ], "publication": { "conference_name": null, "date": "2014 Nov 20", "date_precision": "day", "issue": "", "normalized_date": "2014-11-20", "pages": "5560", "proceedings_title": null, "publisher": "", "title": "Nature communications", "volume": "5", "year": 2014 }, "ssbd": { "database": [], "repository": [] }, "title": "Microhomology-mediated end-joining-dependent integration of donor DNA in cells and animals using TALENs and CRISPR/Cas9.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Thymidine phosphorylase (TP) promotes angiogenesis and metastasis, and confers resistance to anticancer agents in some cancer cell types. We previously reported that TP stimulates the expression of interleukin (IL)-8 in human KB cancer cells by an unknown mechanism. A mutation in the nuclear factor (NF)kappaB binding site of the IL-8 promoter suppressed promoter activity in KB/TP cells that overexpress TP. Specifically inhibiting NFkappaB by using BY11-7082 also suppressed TP-induced IL-8 promoter activity and IL-8 expression. Moreover, TP overexpression led to the activation of NFkappaB and an upregulation in the expression of its target genes, and increased phosphorylated IKKalpha/beta protein levels, while promoting IkappaBalpha degradation as well as p65 phosphorylation and nuclear localization. The activation of NFkappaB in KB/TP cells was suppressed by the antioxidants N-acetylcysteine and EUK-8. In addition, in gastric cancer tissue samples, the expression of the NFkappaB-regulated genes, including IL-8, IL-6, and fibronectin-1 was positively correlated with TP expression. These findings indicate that reactive oxygen species mediated NFkappaB activation by TP increases the expression of genes that promote angiogenesis and metastasis in gastric cancer.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Sho", "last_name": "Tabata", "name": null }, { "creator_type": "author", "first_name": "Ryuji", "last_name": "Ikeda", "name": null }, { "creator_type": "author", "first_name": "Masatatsu", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Shunji", "last_name": "Shimaoka", "name": null }, { "creator_type": "author", "first_name": "Naofumi", "last_name": "Mukaida", "name": null }, { "creator_type": "author", "first_name": "Yasuo", "last_name": "Takeda", "name": null }, { "creator_type": "author", "first_name": "Katsushi", "last_name": "Yamada", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Tatsuhiko", "last_name": "Furukawa", "name": null }, { "creator_type": "author", "first_name": "Shin-ichi", "last_name": "Akiyama", "name": null } ], "identifiers": { "doi": { "normalized": "10.18632/oncotarget.2242" }, "pmcid": { "normalized": "PMC4279387" }, "pmid": { "normalized": "25350954" } }, "mesh": [ { "descriptor": "Apoptosis", "descriptor_ui": "D017209", "major_topic": false }, { "descriptor": "Blotting, Western", "descriptor_ui": "D015153", "major_topic": false }, { "descriptor": "Cell Proliferation", "descriptor_ui": "D049109", "major_topic": false }, { "descriptor": "Fibronectins", "descriptor_ui": "D005353", "major_topic": false }, { "descriptor": "Gene Expression Regulation, Neoplastic", "descriptor_ui": "D015972", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Interleukin-6", "descriptor_ui": "D015850", "major_topic": false }, { "descriptor": "Interleukin-8", "descriptor_ui": "D016209", "major_topic": false }, { "descriptor": "Neovascularization, Pathologic", "descriptor_ui": "D009389", "major_topic": false }, { "descriptor": "NF-kappa B", "descriptor_ui": "D016328", "major_topic": false }, { "descriptor": "Phosphorylation", "descriptor_ui": "D010766", "major_topic": false }, { "descriptor": "Promoter Regions, Genetic", "descriptor_ui": "D011401", "major_topic": false }, { "descriptor": "Real-Time Polymerase Chain Reaction", "descriptor_ui": "D060888", "major_topic": false }, { "descriptor": "Reverse Transcriptase Polymerase Chain Reaction", "descriptor_ui": "D020133", "major_topic": false }, { "descriptor": "RNA, Messenger", "descriptor_ui": "D012333", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Stomach Neoplasms", "descriptor_ui": "D013274", "major_topic": false }, { "descriptor": "Thymidine Phosphorylase", "descriptor_ui": "D013939", "major_topic": false }, { "descriptor": "Transcriptional Activation", "descriptor_ui": "D015533", "major_topic": false }, { "descriptor": "Tumor Cells, Cultured", "descriptor_ui": "D014407", "major_topic": false } ], "publication": { "conference_name": null, "date": "2014 Nov 15", "date_precision": "day", "issue": "21", "normalized_date": "2014-11-15", "pages": "10473-10485", "proceedings_title": null, "publisher": "", "title": "Oncotarget", "volume": "5", "year": 2014 }, "ssbd": { "database": [], "repository": [] }, "title": "Thymidine phosphorylase activates NFkappaB and stimulates the expression of angiogenic and metastatic factors in human cancer cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: To determine if a method for irrigation and aspiration (I/A) during cataract surgery provides effective removal of ophthalmic viscoelastic device (OVD). METHODS: Japanese porcine eyes were used to evaluate I/A performance with Technique 1 (the I/A tip placed on the center of the anterior surface of the IOL), Technique 2 (the I/A tip alternately pressed near the edge of the IOL optic anterior surface on one side and then the other to tilt the IOL back and forth), and Technique 3 (the I/A tip inserted behind the IOL optic, between it and the posterior capsule). Techniques 1 and 2 were compared using the Miyake-Apple posterior view video technique to visualize the flow of irrigation fluid containing triamcinolone acetonide particles behind the IOL. To check the efficacy of OVD removal from behind the IOL for of all three I/A techniques, OVD with fluorescein beads were inserted inside the lens capsule before implantation of the IOL. After each I/A technique, eyes were prepared for Miyake-Apple viewing and pictures of the lens capsule were taken using fluorescent microscopy. Residual fluorescein beads in the capsular bag were analyzed. RESULTS: Technique 1 resulted in a straight flow of fluid behind the IOL, while Technique 2 resulted in a vortex flow. The average amount of OVD retained inside the capsule after using Technique 2 or 3 was significantly lower than after using Technique 1 (p <0.0001). CONCLUSIONS: Technique 2 proved to remove more effectively fluorescein bead-labelled OVD under the IOL than Technique 1.", "classifications": [ { "id": "Suzuki", "label": "Group Suzuki", "parent": "Takekawa", "type": "group" }, { "id": "Takekawa", "label": "Team Takekawa", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Arisa", "last_name": "Mitani", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Yoshitaka", "last_name": "Tasaka", "name": null }, { "creator_type": "author", "first_name": "Takahiro", "last_name": "Uda", "name": null }, { "creator_type": "author", "first_name": "Yukako", "last_name": "Hiramatsu", "name": null }, { "creator_type": "author", "first_name": "Shiro", "last_name": "Kawasaki", "name": null }, { "creator_type": "author", "first_name": "Yuichi", "last_name": "Ohashi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1186/1471-2415-14-129" }, "pmcid": { "normalized": "PMC4232668" }, "pmid": { "normalized": "25376934" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Capsulorhexis", "descriptor_ui": "D019923", "major_topic": false }, { "descriptor": "Disease Models, Animal", "descriptor_ui": "D004195", "major_topic": true }, { "descriptor": "Drainage", "descriptor_ui": "D004322", "major_topic": false }, { "descriptor": "Fluorescein", "descriptor_ui": "D019793", "major_topic": false }, { "descriptor": "Lens Implantation, Intraocular", "descriptor_ui": "D019654", "major_topic": false }, { "descriptor": "Microspheres", "descriptor_ui": "D008863", "major_topic": false }, { "descriptor": "Phacoemulsification", "descriptor_ui": "D018918", "major_topic": true }, { "descriptor": "Swine", "descriptor_ui": "D013552", "major_topic": false }, { "descriptor": "Therapeutic Irrigation", "descriptor_ui": "D007507", "major_topic": false }, { "descriptor": "Viscoelastic Substances", "descriptor_ui": "D055682", "major_topic": false } ], "publication": { "conference_name": null, "date": "2014 Nov 7", "date_precision": "day", "issue": "", "normalized_date": "2014-11-07", "pages": "129", "proceedings_title": null, "publisher": "", "title": "BMC ophthalmology", "volume": "14", "year": 2014 }, "ssbd": { "database": [], "repository": [] }, "title": "Evaluation of a new method of irrigation and aspiration for removal of ophthalmic viscoelastic device during cataract surgery in a porcine model.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "How spatial and temporal information are integrated to determine the direction of cell migration remains poorly understood. Here, by precise microfluidics emulation of dynamic chemoattractant waves, we demonstrate that, in Dictyostelium, directional movement as well as activation of small guanosine triphosphatase Ras at the leading edge is suppressed when the chemoattractant concentration is decreasing over time. This 'rectification' of directional sensing occurs only at an intermediate range of wave speed and does not require phosphoinositide-3-kinase or F-actin. From modelling analysis, we show that rectification arises naturally in a single-layered incoherent feedforward circuit with zero-order ultrasensitivity. The required stimulus time-window predicts ~5 s transient for directional sensing response close to Ras activation and inhibitor diffusion typical for protein in the cytosol. We suggest that the ability of Dictyostelium cells to move only in the wavefront is closely associated with rectification of adaptive response combined with local activation and global inhibition.", "classifications": [ { "id": "Ishihara", "label": "Group Ishihara", "parent": "Sawai", "type": "group" }, { "id": "Sawai", "label": "Group Sawai", "parent": "Sawai", "type": "group" }, { "id": "Sawai", "label": "Team Sawai", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Akihiko", "last_name": "Nakajima", "name": null }, { "creator_type": "author", "first_name": "Shuji", "last_name": "Ishihara", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Imoto", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Sawai", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/ncomms6367" }, "pmcid": { "normalized": "PMC4272253" }, "pmid": { "normalized": "25373620" } }, "mesh": [ { "descriptor": "Cell Movement", "descriptor_ui": "D002465", "major_topic": false }, { "descriptor": "Chemotaxis", "descriptor_ui": "D002633", "major_topic": false }, { "descriptor": "Cyclic AMP", "descriptor_ui": "D000242", "major_topic": false }, { "descriptor": "Dictyostelium", "descriptor_ui": "D004023", "major_topic": false }, { "descriptor": "Microfluidics", "descriptor_ui": "D044085", "major_topic": true }, { "descriptor": "Models, Biological", "descriptor_ui": "D008954", "major_topic": false }, { "descriptor": "ras Proteins", "descriptor_ui": "D018631", "major_topic": false }, { "descriptor": "Time Factors", "descriptor_ui": "D013997", "major_topic": false } ], "publication": { "conference_name": null, "date": "2014 Nov 6", "date_precision": "day", "issue": "", "normalized_date": "2014-11-06", "pages": "5367", "proceedings_title": null, "publisher": "", "title": "Nature communications", "volume": "5", "year": 2014 }, "ssbd": { "database": [], "repository": [] }, "title": "Rectified directional sensing in long-range cell migration.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "L-cysteine is essential for virtually all living organisms, from bacteria to higher eukaryotes. Besides having a role in the synthesis of virtually all proteins and of taurine, cysteamine, glutathione, and other redox-regulating proteins, L-cysteine has important functions under anaerobic/microaerophilic conditions. In anaerobic or microaerophilic protozoan parasites, such as Entamoeba histolytica, L-cysteine has been implicated in growth, attachment, survival, and protection from oxidative stress. However, a specific role of this amino acid or related metabolic intermediates is not well understood. In this study, using stable-isotope-labeled L-cysteine and capillary electrophoresis-time of flight mass spectrometry, we investigated the metabolism of L-cysteine in E. histolytica. [U-(13)C3, (15)N]L-cysteine was rapidly metabolized into three unknown metabolites, besides L-cystine and L-alanine. These metabolites were identified as thiazolidine-4-carboxylic acid (T4C), 2-methyl thiazolidine-4-carboxylic acid (MT4C), and 2-ethyl-thiazolidine-4-carboxylic acid (ET4C), the condensation products of L-cysteine with aldehydes. We demonstrated that these 2-(R)-thiazolidine-4-carboxylic acids serve for storage of L-cysteine. Liberation of L-cysteine occurred when T4C was incubated with amebic lysates, suggesting enzymatic degradation of these L-cysteine derivatives. Furthermore, T4C and MT4C significantly enhanced trophozoite growth and reduced intracellular reactive oxygen species (ROS) levels when it was added to cultures, suggesting that 2-(R)-thiazolidine-4-carboxylic acids are involved in the defense against oxidative stress. IMPORTANCE: Amebiasis is a human parasitic disease caused by the protozoan parasite Entamoeba histolytica. In this parasite, L-cysteine is the principal low-molecular-weight thiol and is assumed to play a significant role in supplying the amino acid during trophozoite invasion, particularly when the parasites move from the anaerobic intestinal lumen to highly oxygenated tissues in the intestine and the liver. It is well known that E. histolytica needs a comparatively high concentration of L-cysteine for its axenic cultivation. However, the reason for and the metabolic fate of L-cysteine in this parasite are not well understood. Here, using a metabolomic and stable-isotope-labeled approach, we investigated the metabolic fate of this amino acid in these parasites. We found that L-cysteine inside the cell rapidly reacts with aldehydes to form 2-(R)-thiazolidine-4-carboxylic acid. We showed that these 2-(R)-thiazolidine-4-carboxylic derivatives serve as an L-cysteine source, promote growth, and protect cells against oxidative stress by scavenging aldehydes and reducing the ROS level. Our findings represent the first demonstration of 2-(R)-thiazolidine-4-carboxylic acids and their roles in protozoan parasites.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Ghulam", "last_name": "Jeelani", "name": null }, { "creator_type": "author", "first_name": "Dan", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Haruo", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Nozaki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1128/mbio.01995-14" }, "pmcid": { "normalized": "PMC4222106" }, "pmid": { "normalized": "25370494" } }, "mesh": [ { "descriptor": "Cysteine", "descriptor_ui": "D003545", "major_topic": false }, { "descriptor": "Entamoeba histolytica", "descriptor_ui": "D004748", "major_topic": false }, { "descriptor": "Isotope Labeling", "descriptor_ui": "D007553", "major_topic": false }, { "descriptor": "Mass Spectrometry", "descriptor_ui": "D013058", "major_topic": false }, { "descriptor": "Molecular Sequence Data", "descriptor_ui": "D008969", "major_topic": false }, { "descriptor": "Oxidative Stress", "descriptor_ui": "D018384", "major_topic": false }, { "descriptor": "Sequence Analysis, DNA", "descriptor_ui": "D017422", "major_topic": false } ], "publication": { "conference_name": null, "date": "2014 Nov 4", "date_precision": "day", "issue": "6", "normalized_date": "2014-11-04", "pages": "e01995", "proceedings_title": null, "publisher": "", "title": "mBio", "volume": "5", "year": 2014 }, "ssbd": { "database": [], "repository": [] }, "title": "Mass spectrometric analysis of L-cysteine metabolism: physiological role and fate of L-cysteine in the enteric protozoan parasite Entamoeba histolytica.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Quinonoid dihydropteridine reductase (QDPR) catalyzes the regeneration of tetrahydrobiopterin (BH4), a cofactor for monoamine synthesis, phenylalanine hydroxylation and nitric oxide production. Here, we produced and analyzed a transgenic Qdpr(-/-) mouse model. Unexpectedly, the BH4 contents in the Qdpr(-/-) mice were not decreased and even increased in some tissues, whereas those of the oxidized form dihydrobiopterin (BH2) were significantly increased. We demonstrated that unlike the wild-type mice, dihydrofolate reductase regenerated BH4 from BH2 in the mutants. Furthermore, we revealed wide alterations in folate-associated metabolism in the Qdpr(-/-) mice, which suggests an interconnection between folate and biopterin metabolism in the transgenic mouse model.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Feng", "last_name": "Xu", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Sudo", "name": null }, { "creator_type": "author", "first_name": "Sho", "last_name": "Sanechika", "name": null }, { "creator_type": "author", "first_name": "Junpei", "last_name": "Yamashita", "name": null }, { "creator_type": "author", "first_name": "Sho", "last_name": "Shimaguchi", "name": null }, { "creator_type": "author", "first_name": "Shun-ichiro", "last_name": "Honda", "name": null }, { "creator_type": "author", "first_name": "Chiho", "last_name": "Sumi-Ichinose", "name": null }, { "creator_type": "author", "first_name": "Masayo", "last_name": "Mori-Kojima", "name": null }, { "creator_type": "author", "first_name": "Rieko", "last_name": "Nakata", "name": null }, { "creator_type": "author", "first_name": "Tadaomi", "last_name": "Furuta", "name": null }, { "creator_type": "author", "first_name": "Minoru", "last_name": "Sakurai", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Sugimoto", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Kazunao", "last_name": "Kondo", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Ichinose", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.febslet.2014.09.004" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "25240194" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Biopterins", "descriptor_ui": "D001708", "major_topic": false }, { "descriptor": "Folic Acid", "descriptor_ui": "D005492", "major_topic": false }, { "descriptor": "Kinetics", "descriptor_ui": "D007700", "major_topic": false }, { "descriptor": "Metabolomics", "descriptor_ui": "D055432", "major_topic": false }, { "descriptor": "Methotrexate", "descriptor_ui": "D008727", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Transgenic", "descriptor_ui": "D008822", "major_topic": false }, { "descriptor": "Oxidoreductases", "descriptor_ui": "D010088", "major_topic": false }, { "descriptor": "Tetrahydrofolate Dehydrogenase", "descriptor_ui": "D013762", "major_topic": false } ], "publication": { "conference_name": null, "date": "2014 Nov 3", "date_precision": "day", "issue": "21", "normalized_date": "2014-11-03", "pages": "3924-3931", "proceedings_title": null, "publisher": "", "title": "FEBS letters", "volume": "588", "year": 2014 }, "ssbd": { "database": [], "repository": [] }, "title": "Disturbed biopterin and folate metabolism in the Qdpr-deficient mouse.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Nanoparticle manipulation is of increasing interest, since they can report single molecule-level measurements of the cellular environment. Until now, however, intracellular nanoparticle locations have been essentially uncontrollable. Here we show that by infusing a gold ion solution, focused laser light-induced photoreduction allows in situ fabrication of gold nanoparticles at precise locations. The resulting particles are pure gold nanocrystals, distributed throughout the laser focus at sizes ranging from 2 to 20 nm, and remain in place even after removing the gold solution. We demonstrate the spatial control by scanning a laser beam to write characters in gold inside a cell. Plasmonically enhanced molecular signals could be detected from nanoparticles, allowing their use as nano-chemical probes at targeted locations inside the cell, with intracellular molecular feedback. Such light-based control of the intracellular particle generation reaction also offers avenues for in situ plasmonic device creation in organic targets, and may eventually link optical and electron microscopy.", "classifications": [ { "id": "Fujita", "label": "Group Fujita", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Nicholas I.", "last_name": "Smith", "name": null }, { "creator_type": "author", "first_name": "Kentaro", "last_name": "Mochizuki", "name": null }, { "creator_type": "author", "first_name": "Hirohiko", "last_name": "Niioka", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Ichikawa", "name": null }, { "creator_type": "author", "first_name": "Nicolas", "last_name": "Pavillon", "name": null }, { "creator_type": "author", "first_name": "Alison J.", "last_name": "Hobro", "name": null }, { "creator_type": "author", "first_name": "Jun", "last_name": "Ando", "name": null }, { "creator_type": "author", "first_name": "Katsumasa", "last_name": "Fujita", "name": null }, { "creator_type": "author", "first_name": "Yutaro", "last_name": "Kumagai", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/ncomms6144" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "25298313" } }, "mesh": [ { "descriptor": "Gold", "descriptor_ui": "D006046", "major_topic": true }, { "descriptor": "Lasers", "descriptor_ui": "D007834", "major_topic": true }, { "descriptor": "Metal Nanoparticles", "descriptor_ui": "D053768", "major_topic": false }, { "descriptor": "Oxidation-Reduction", "descriptor_ui": "D010084", "major_topic": false } ], "publication": { "conference_name": null, "date": "2014 Oct 9", "date_precision": "day", "issue": "", "normalized_date": "2014-10-09", "pages": "5144", "proceedings_title": null, "publisher": "", "title": "Nature communications", "volume": "5", "year": 2014 }, "ssbd": { "database": [], "repository": [] }, "title": "Laser-targeted photofabrication of gold nanoparticles inside cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "GWAS have identified a breast cancer susceptibility locus on 2q35. Here we report the fine mapping of this locus using data from 101,943 subjects from 50 case-control studies. We genotype 276 SNPs using the 'iCOGS' genotyping array and impute genotypes for a further 1,284 using 1000 Genomes Project data. All but two, strongly correlated SNPs (rs4442975 G/T and rs6721996 G/A) are excluded as candidate causal variants at odds against >100:1. The best functional candidate, rs4442975, is associated with oestrogen receptor positive (ER+) disease with an odds ratio (OR) in Europeans of 0.85 (95% confidence interval=0.84-0.87; P=1.7 × 10(-43)) per t-allele. This SNP flanks a transcriptional enhancer that physically interacts with the promoter of IGFBP5 (encoding insulin-like growth factor-binding protein 5) and displays allele-specific gene expression, FOXA1 binding and chromatin looping. Evidence suggests that the g-allele confers increased breast cancer susceptibility through relative downregulation of IGFBP5, a gene with known roles in breast cell biology.", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Maya", "last_name": "Ghoussaini", "name": null }, { "creator_type": "author", "first_name": "Stacey L.", "last_name": "Edwards", "name": null }, { "creator_type": "author", "first_name": "Kyriaki", "last_name": "Michailidou", "name": null }, { "creator_type": "author", "first_name": "Silje", "last_name": "Nord", "name": null }, { "creator_type": "author", "first_name": "Richard", "last_name": "Cowper-Sal Lari", "name": null }, { "creator_type": "author", "first_name": "Kinjal", "last_name": "Desai", "name": null }, { "creator_type": "author", "first_name": "Siddhartha", "last_name": "Kar", "name": null }, { "creator_type": "author", "first_name": "Kristine M.", "last_name": "Hillman", "name": null }, { "creator_type": "author", "first_name": "Susanne", "last_name": "Kaufmann", "name": null }, { "creator_type": "author", "first_name": "Dylan M.", "last_name": "Glubb", "name": null }, { "creator_type": "author", "first_name": "Jonathan", "last_name": "Beesley", "name": null }, { "creator_type": "author", "first_name": "Joe", "last_name": "Dennis", "name": null }, { "creator_type": "author", "first_name": "Manjeet K.", "last_name": "Bolla", "name": null }, { "creator_type": "author", "first_name": "Qin", "last_name": "Wang", "name": null }, { "creator_type": "author", "first_name": "Ed", "last_name": "Dicks", "name": null }, { "creator_type": "author", "first_name": "Qi", "last_name": "Guo", "name": null }, { "creator_type": "author", "first_name": "Marjanka K.", "last_name": "Schmidt", "name": null }, { "creator_type": "author", "first_name": "Mitul", "last_name": "Shah", "name": null }, { "creator_type": "author", "first_name": "Robert", "last_name": "Luben", "name": null }, { "creator_type": "author", "first_name": "Judith", "last_name": "Brown", "name": null }, { "creator_type": "author", "first_name": "Kamila", "last_name": "Czene", "name": null }, { "creator_type": "author", "first_name": "Hatef", "last_name": "Darabi", "name": null }, { "creator_type": "author", "first_name": "Mikael", "last_name": "Eriksson", "name": null }, { "creator_type": "author", "first_name": "Daniel", "last_name": "Klevebring", "name": null }, { "creator_type": "author", "first_name": "Stig E.", "last_name": "Bojesen", "name": null }, { "creator_type": "author", "first_name": "Børge G.", "last_name": "Nordestgaard", "name": null }, { "creator_type": "author", "first_name": "Sune F.", "last_name": "Nielsen", "name": null }, { "creator_type": "author", "first_name": "Henrik", "last_name": "Flyger", "name": null }, { "creator_type": "author", "first_name": "Diether", "last_name": "Lambrechts", "name": null }, { "creator_type": "author", "first_name": "Bernard", "last_name": "Thienpont", "name": null }, { "creator_type": "author", "first_name": "Patrick", "last_name": "Neven", "name": null }, { "creator_type": "author", "first_name": "Hans", "last_name": "Wildiers", "name": null }, { "creator_type": "author", "first_name": "Annegien", "last_name": "Broeks", "name": null }, { "creator_type": "author", "first_name": "Laura J.", "last_name": "Van't Veer", "name": null }, { "creator_type": "author", "first_name": "Emiel J.", "last_name": "Th Rutgers", "name": null }, { "creator_type": "author", "first_name": "Fergus J.", "last_name": "Couch", "name": null }, { "creator_type": "author", "first_name": "Janet E.", "last_name": "Olson", "name": null }, { "creator_type": "author", "first_name": "Emily", "last_name": "Hallberg", "name": null }, { "creator_type": "author", "first_name": "Celine", "last_name": "Vachon", "name": null }, { "creator_type": "author", "first_name": "Jenny", "last_name": "Chang-Claude", "name": null }, { "creator_type": "author", "first_name": "Anja", "last_name": "Rudolph", "name": null }, { "creator_type": "author", "first_name": "Petra", "last_name": "Seibold", "name": null }, { "creator_type": "author", "first_name": "Dieter", "last_name": "Flesch-Janys", "name": null }, { "creator_type": "author", "first_name": "Julian", "last_name": "Peto", "name": null }, { "creator_type": "author", "first_name": "Isabel", "last_name": "Dos-Santos-Silva", "name": null }, { "creator_type": "author", "first_name": "Lorna", "last_name": "Gibson", "name": null }, { "creator_type": "author", "first_name": "Heli", "last_name": "Nevanlinna", "name": null }, { "creator_type": "author", "first_name": "Taru A.", "last_name": "Muranen", "name": null }, { "creator_type": "author", "first_name": "Kristiina", "last_name": "Aittomäki", "name": null }, { "creator_type": "author", "first_name": "Carl", "last_name": "Blomqvist", "name": null }, { "creator_type": "author", "first_name": "Per", "last_name": "Hall", "name": null }, { "creator_type": "author", "first_name": "Jingmei", "last_name": "Li", "name": null }, { "creator_type": "author", "first_name": "Jianjun", "last_name": "Liu", "name": null }, { "creator_type": "author", "first_name": "Keith", "last_name": "Humphreys", "name": null }, { "creator_type": "author", "first_name": "Daehee", "last_name": "Kang", "name": null }, { "creator_type": "author", "first_name": "Ji-Yeob", "last_name": "Choi", "name": null }, { "creator_type": "author", "first_name": "Sue K.", "last_name": "Park", "name": null }, { "creator_type": "author", "first_name": "Dong-Young", "last_name": "Noh", "name": null }, { "creator_type": "author", "first_name": "Keitaro", "last_name": "Matsuo", "name": null }, { "creator_type": "author", "first_name": "Hidemi", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Hiroji", "last_name": "Iwata", "name": null 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"Tseng", "name": null }, { "creator_type": "author", "first_name": "David", "last_name": "Van Den Berg", "name": null }, { "creator_type": "author", "first_name": "Daniel O.", "last_name": "Stram", "name": null }, { "creator_type": "author", "first_name": "Javier", "last_name": "Benitez", "name": null }, { "creator_type": "author", "first_name": "M. Pilar", "last_name": "Zamora", "name": null }, { "creator_type": "author", "first_name": "Jose Ignacio Arias", "last_name": "Perez", "name": null }, { "creator_type": "author", "first_name": "Primitiva", "last_name": "Menéndez", "name": null }, { "creator_type": "author", "first_name": "Xiao-Ou", "last_name": "Shu", "name": null }, { "creator_type": "author", "first_name": "Wei", "last_name": "Lu", "name": null }, { "creator_type": "author", "first_name": "Yu-Tang", "last_name": "Gao", "name": null }, { "creator_type": "author", "first_name": "Qiuyin", "last_name": "Cai", "name": null }, { "creator_type": "author", "first_name": "Angela", "last_name": "Cox", "name": null }, { "creator_type": "author", "first_name": "Simon S.", "last_name": "Cross", "name": null }, { "creator_type": "author", "first_name": "Malcolm W. R.", "last_name": "Reed", "name": null }, { "creator_type": "author", "first_name": "Irene L.", "last_name": "Andrulis", "name": null }, { "creator_type": "author", "first_name": "Julia A.", "last_name": "Knight", "name": null }, { "creator_type": "author", "first_name": "Gord", "last_name": "Glendon", "name": null }, { "creator_type": "author", "first_name": "Sandrine", "last_name": "Tchatchou", "name": null }, { "creator_type": "author", "first_name": "Elinor J.", "last_name": "Sawyer", "name": null }, { "creator_type": "author", "first_name": "Ian", "last_name": "Tomlinson", "name": null }, { "creator_type": "author", "first_name": "Michael J.", "last_name": "Kerin", "name": null }, { "creator_type": "author", "first_name": "Nicola", "last_name": "Miller", "name": null }, { "creator_type": "author", "first_name": "Christopher A.", "last_name": "Haiman", "name": null }, { "creator_type": "author", "first_name": "Brian E.", "last_name": "Henderson", "name": null }, { "creator_type": "author", "first_name": "Fredrick", "last_name": "Schumacher", "name": null }, { "creator_type": "author", "first_name": "Loic", "last_name": "Le Marchand", "name": null }, { "creator_type": "author", "first_name": "Annika", "last_name": "Lindblom", "name": null }, { "creator_type": "author", "first_name": "Sara", "last_name": "Margolin", "name": null }, { "creator_type": "author", "first_name": "Soo Hwang", "last_name": "Teo", "name": null }, { "creator_type": "author", "first_name": "Cheng Har", "last_name": "Yip", "name": null }, { "creator_type": "author", "first_name": "Daphne S. C.", "last_name": "Lee", "name": null }, { "creator_type": "author", "first_name": "Tien Y.", "last_name": "Wong", "name": null }, { "creator_type": "author", "first_name": "Maartje J.", "last_name": "Hooning", "name": null }, { "creator_type": "author", "first_name": "John W. M.", "last_name": "Martens", "name": null }, { "creator_type": "author", "first_name": "J. Margriet", "last_name": "Collée", "name": null }, { "creator_type": "author", "first_name": "Carolien H. M.", "last_name": "van Deurzen", "name": null }, { "creator_type": "author", "first_name": "John L.", "last_name": "Hopper", "name": null }, { "creator_type": "author", "first_name": "Melissa C.", "last_name": "Southey", "name": null }, { "creator_type": "author", "first_name": "Helen", "last_name": "Tsimiklis", "name": null }, { "creator_type": "author", "first_name": "Miroslav K.", "last_name": "Kapuscinski", "name": null }, { "creator_type": "author", "first_name": "Chen-Yang", "last_name": "Shen", "name": null }, { "creator_type": "author", "first_name": "Pei-Ei", "last_name": "Wu", "name": null }, { "creator_type": "author", "first_name": "Jyh-Cherng", "last_name": "Yu", "name": null }, { "creator_type": "author", "first_name": "Shou-Tung", "last_name": "Chen", "name": null }, { "creator_type": "author", "first_name": "Grethe Grenaker", "last_name": "Alnæs", "name": null }, { "creator_type": "author", "first_name": "Anne-Lise", "last_name": "Borresen-Dale", "name": null }, { "creator_type": "author", "first_name": "Graham G.", "last_name": "Giles", "name": null }, { "creator_type": "author", "first_name": "Roger L.", "last_name": "Milne", "name": null }, { "creator_type": "author", "first_name": "Catriona", "last_name": "McLean", "name": null }, { "creator_type": "author", "first_name": "Kenneth", "last_name": "Muir", "name": null }, { "creator_type": "author", "first_name": "Artitaya", "last_name": "Lophatananon", "name": null }, { "creator_type": "author", "first_name": "Sarah", "last_name": "Stewart-Brown", "name": null }, { "creator_type": "author", "first_name": "Pornthep", "last_name": "Siriwanarangsan", "name": null }, { "creator_type": "author", "first_name": "Mikael", "last_name": "Hartman", "name": null }, { "creator_type": "author", "first_name": "Hui", "last_name": "Miao", "name": null }, { "creator_type": "author", "first_name": "Shaik Ahmad Bin Syed", "last_name": "Buhari", "name": null }, { "creator_type": "author", "first_name": "Yik Ying", "last_name": "Teo", "name": null }, { "creator_type": "author", "first_name": "Peter A.", "last_name": "Fasching", "name": null }, { "creator_type": "author", "first_name": "Lothar", "last_name": "Haeberle", "name": null }, { "creator_type": "author", "first_name": "Arif B.", "last_name": "Ekici", "name": null }, { "creator_type": "author", "first_name": "Matthias W.", "last_name": "Beckmann", "name": null }, { "creator_type": "author", "first_name": "Hermann", "last_name": "Brenner", "name": null }, { "creator_type": "author", "first_name": "Aida Karina", "last_name": "Dieffenbach", "name": null }, { "creator_type": "author", "first_name": "Volker", "last_name": "Arndt", "name": null }, { "creator_type": "author", "first_name": "Christa", "last_name": "Stegmaier", "name": null }, { "creator_type": "author", "first_name": "Anthony", "last_name": "Swerdlow", "name": null }, { "creator_type": "author", "first_name": "Alan", "last_name": "Ashworth", "name": null }, { "creator_type": "author", "first_name": "Nick", "last_name": "Orr", "name": null }, { "creator_type": "author", "first_name": "Minouk J.", "last_name": "Schoemaker", "name": null }, { "creator_type": "author", "first_name": "Montserrat", "last_name": "García-Closas", "name": null }, { "creator_type": "author", "first_name": "Jonine", "last_name": "Figueroa", "name": null }, { "creator_type": "author", "first_name": "Stephen J.", "last_name": "Chanock", "name": null }, { "creator_type": "author", "first_name": "Jolanta", "last_name": "Lissowska", "name": null }, { "creator_type": "author", "first_name": "Jacques", "last_name": "Simard", "name": null }, { "creator_type": "author", "first_name": "Mark S.", "last_name": "Goldberg", "name": null }, { "creator_type": "author", "first_name": "France", "last_name": "Labrèche", "name": null }, { "creator_type": "author", "first_name": "Martine", "last_name": "Dumont", "name": null }, { "creator_type": "author", "first_name": "Robert", "last_name": "Winqvist", "name": null }, { "creator_type": "author", "first_name": "Katri", "last_name": "Pylkäs", "name": null }, { "creator_type": "author", "first_name": "Arja", "last_name": "Jukkola-Vuorinen", "name": null }, { "creator_type": "author", "first_name": "Hiltrud", "last_name": "Brauch", "name": null }, { "creator_type": "author", "first_name": "Thomas", "last_name": "Brüning", "name": null }, { "creator_type": "author", "first_name": "Yon-Dschun", "last_name": "Koto", "name": null }, { "creator_type": "author", "first_name": "Paolo", "last_name": "Radice", "name": null }, { "creator_type": "author", "first_name": "Paolo", "last_name": "Peterlongo", "name": null }, { "creator_type": "author", "first_name": "Bernardo", "last_name": "Bonanni", "name": null }, { "creator_type": "author", "first_name": "Sara", "last_name": "Volorio", "name": null }, { "creator_type": "author", "first_name": "Thilo", "last_name": "Dörk", "name": null }, { "creator_type": "author", "first_name": "Natalia V.", "last_name": "Bogdanova", "name": null }, { "creator_type": "author", "first_name": "Sonja", "last_name": "Helbig", "name": null }, { "creator_type": "author", "first_name": "Arto", "last_name": "Mannermaa", "name": null }, { "creator_type": "author", "first_name": "Vesa", "last_name": "Kataja", "name": null }, { "creator_type": "author", "first_name": "Veli-Matti", "last_name": "Kosma", "name": null }, { "creator_type": "author", "first_name": "Jaana M.", "last_name": "Hartikainen", "name": null }, { "creator_type": "author", "first_name": "Peter", "last_name": "Devilee", "name": null }, { "creator_type": "author", "first_name": "Robert A. E. M.", "last_name": "Tollenaar", "name": null }, { "creator_type": "author", "first_name": "Caroline", "last_name": "Seynaeve", "name": null }, { "creator_type": "author", "first_name": "Christi J.", "last_name": "Van Asperen", "name": null }, { "creator_type": "author", "first_name": "Anna", "last_name": "Jakubowska", "name": null }, { "creator_type": "author", "first_name": "Jan", "last_name": "Lubinski", "name": null }, { "creator_type": "author", "first_name": "Katarzyna", "last_name": "Jaworska-Bieniek", "name": null }, { "creator_type": "author", "first_name": "Katarzyna", "last_name": "Durda", "name": null }, { "creator_type": "author", "first_name": "Susan", "last_name": "Slager", "name": null }, { "creator_type": "author", "first_name": "Amanda E.", "last_name": "Toland", "name": null }, { "creator_type": "author", "first_name": "Christine B.", "last_name": "Ambrosone", "name": null }, { "creator_type": "author", "first_name": "Drakoulis", "last_name": "Yannoukakos", "name": null }, { "creator_type": "author", "first_name": "Suleeporn", "last_name": "Sangrajrang", "name": null }, { "creator_type": "author", "first_name": "Valerie", "last_name": "Gaborieau", "name": null }, { "creator_type": "author", "first_name": "Paul", "last_name": "Brennan", "name": null }, { "creator_type": "author", "first_name": "James", "last_name": "McKay", "name": null }, { "creator_type": "author", "first_name": "Ute", "last_name": "Hamann", "name": null }, { "creator_type": "author", "first_name": "Diana", "last_name": "Torres", "name": null }, { "creator_type": "author", "first_name": "Wei", "last_name": "Zheng", "name": null }, { "creator_type": "author", "first_name": "Jirong", "last_name": "Long", "name": null }, { "creator_type": "author", "first_name": "Hoda", "last_name": "Anton-Culver", "name": null }, { "creator_type": "author", "first_name": "Susan L.", "last_name": "Neuhausen", "name": null }, { "creator_type": "author", "first_name": "Craig", "last_name": "Luccarini", "name": null }, { "creator_type": "author", "first_name": "Caroline", "last_name": "Baynes", "name": null }, { "creator_type": "author", "first_name": "Shahana", "last_name": "Ahmed", "name": null }, { "creator_type": "author", "first_name": "Mel", "last_name": "Maranian", "name": null }, { "creator_type": "author", "first_name": "Catherine S.", "last_name": "Healey", "name": null }, { "creator_type": "author", "first_name": "Anna", "last_name": "González-Neira", "name": null }, { "creator_type": "author", "first_name": "Guillermo", "last_name": "Pita", "name": null }, { "creator_type": "author", "first_name": "M. Rosario", "last_name": "Alonso", "name": null }, { "creator_type": "author", "first_name": "Nuria", "last_name": "Alvarez", "name": null }, { "creator_type": "author", "first_name": "Daniel", "last_name": "Herrero", "name": null }, { "creator_type": "author", "first_name": "Daniel C.", "last_name": "Tessier", "name": null }, { "creator_type": "author", "first_name": "Daniel", "last_name": "Vincent", "name": null }, { "creator_type": "author", "first_name": "Francois", "last_name": "Bacot", "name": null }, { "creator_type": "author", "first_name": "Ines", "last_name": "de Santiago", "name": null }, { "creator_type": "author", "first_name": "Jason", "last_name": "Carroll", "name": null }, { "creator_type": "author", "first_name": "Carlos", "last_name": "Caldas", "name": null }, { "creator_type": "author", "first_name": "Melissa A.", "last_name": "Brown", "name": null }, { "creator_type": "author", "first_name": "Mathieu", "last_name": "Lupien", "name": null }, { "creator_type": "author", "first_name": "Vessela N.", "last_name": "Kristensen", "name": null }, { "creator_type": "author", "first_name": "Paul D. P.", "last_name": "Pharoah", "name": null }, { "creator_type": "author", "first_name": "Georgia", "last_name": "Chenevix-Trench", "name": null }, { "creator_type": "author", "first_name": "Juliet D.", "last_name": "French", "name": null }, { "creator_type": "author", "first_name": "Douglas F.", "last_name": "Easton", "name": null }, { "creator_type": "author", "first_name": "Alison M.", "last_name": "Dunning", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/ncomms5999" }, "pmcid": { "normalized": "PMC4321900" }, "pmid": { "normalized": "25248036" } }, "mesh": [ { "descriptor": "Breast Neoplasms", "descriptor_ui": "D001943", "major_topic": false }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Chromatin", "descriptor_ui": "D002843", "major_topic": false }, { "descriptor": "Chromosomes, Human, Pair 2", "descriptor_ui": "D002889", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Genetic Predisposition to Disease", "descriptor_ui": "D020022", "major_topic": false }, { "descriptor": "Hepatocyte Nuclear Factor 3-alpha", "descriptor_ui": "D051541", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Insulin-Like Growth Factor Binding Protein 5", "descriptor_ui": "D018975", "major_topic": false }, { "descriptor": "MCF-7 Cells", "descriptor_ui": "D061986", "major_topic": false }, { "descriptor": "Polymorphism, Single Nucleotide", "descriptor_ui": "D020641", "major_topic": false }, { "descriptor": "Promoter Regions, Genetic", "descriptor_ui": "D011401", "major_topic": false }, { "descriptor": "RNA, Messenger", "descriptor_ui": "D012333", "major_topic": false } ], "publication": { "conference_name": null, "date": "2014 Sep 23", "date_precision": "day", "issue": "", "normalized_date": "2014-09-23", "pages": "4999", "proceedings_title": null, "publisher": "", "title": "Nature communications", "volume": "4", "year": 2014 }, "ssbd": { "database": [], "repository": [] }, "title": "Evidence that breast cancer risk at the 2q35 locus is mediated through IGFBP5 regulation.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "To understand the morphogenetic mechanisms of organ development and regeneration, it is essential to clarify the inter-hierarchical relationship between microscopic, molecular/cellular activities and organ-level tissue deformation dynamics. While the former have been studied for several decades, the latter - macroscopic geometrical information about physical tissue deformation - is often missing, especially for many vertebrates. This is mainly because live recording of detailed cell behaviors in whole tissues during vertebrate organogenesis is technically difficult. In this study, we have developed a novel method that combines snapshot lineage tracing with Bayesian statistical estimation to construct whole-organ deformation maps from landmark data on limited numbers of space-time points. Following the validation of the method using artificially generated data sets, we applied it to the analysis of tissue deformation dynamics in chick limb development. A quantitative tissue deformation map for St.23-St.24 has been constructed, and its precision has been proven by evaluating its predictive performance. Geometrical analyses of the map have revealed a spatially heterogeneous volume growth pattern that is consistent with the expression pattern of a major morphogen and anisotropic tissue deformation along an axis. Thus, our method enables deformation dynamics analysis in organogenesis using practical lineage marking techniques.", "classifications": [ { "id": "Morishita", "label": "Group Morishita", "parent": "Morishita", "type": "group" }, { "id": "Morishita", "label": "Team Morishita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yoshihiro", "last_name": "Morishita", "name": null }, { "creator_type": "author", "first_name": "Takayuki", "last_name": "Suzuki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.jtbi.2014.04.027" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "24810841" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Datasets as Topic", "descriptor_ui": "D066264", "major_topic": false }, { "descriptor": "Embryonic Development", "descriptor_ui": "D047108", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Models, Biological", "descriptor_ui": "D008954", "major_topic": true }, { "descriptor": "Organogenesis", "descriptor_ui": "D038081", "major_topic": false } ], "publication": { "conference_name": null, "date": "2014 Sep 21", "date_precision": "day", "issue": "", "normalized_date": "2014-09-21", "pages": "74-85", "proceedings_title": null, "publisher": "", "title": "Journal of theoretical biology", "volume": "357", "year": 2014 }, "ssbd": { "database": [], "repository": [] }, "title": "Bayesian inference of whole-organ deformation dynamics from limited space-time point data.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Trifluoromethylation of propargylic alcohols to provide (Z)-alpha-trifluoromethylated enones and beta-unsubstituted alpha-trifluoromethylated enones proceeded with high yield and selectivity in the presence of CuI/Re2O7. The Z isomer was formed under kinetic control, though it is less stable than the E isomer in terms of steric repulsion.", "classifications": [ { "id": "Sodeoka", "label": "Group Sodeoka", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Hiromichi", "last_name": "Egami", "name": null }, { "creator_type": "author", "first_name": "Takafumi", "last_name": "Ide", "name": null }, { "creator_type": "author", "first_name": "Masashi", "last_name": "Fujita", "name": null }, { "creator_type": "author", "first_name": "Toshifumi", "last_name": "Tojo", "name": null }, { "creator_type": "author", "first_name": "Yoshitaka", "last_name": "Hamashima", "name": null }, { "creator_type": "author", "first_name": "Mikiko", "last_name": "Sodeoka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/chem.201403447" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "25077456" } }, "mesh": [ { "descriptor": "Alkynes", "descriptor_ui": "D000480", "major_topic": false }, { "descriptor": "Catalysis", "descriptor_ui": "D002384", "major_topic": false }, { "descriptor": "Copper", "descriptor_ui": "D003300", "major_topic": false }, { "descriptor": "Ketones", "descriptor_ui": "D007659", "major_topic": false }, { "descriptor": "Methylation", "descriptor_ui": "D008745", "major_topic": false }, { "descriptor": "Molecular Structure", "descriptor_ui": "D015394", "major_topic": false }, { "descriptor": "Propanols", "descriptor_ui": "D020005", "major_topic": false }, { "descriptor": "Rhenium", "descriptor_ui": "D012211", "major_topic": false }, { "descriptor": "Stereoisomerism", "descriptor_ui": "D013237", "major_topic": false } ], "publication": { "conference_name": null, "date": "2014 Sep 15", "date_precision": "day", "issue": "38", "normalized_date": "2014-09-15", "pages": "12061-12065", "proceedings_title": null, "publisher": "", "title": "Chemistry (Weinheim an der Bergstrasse, Germany)", "volume": "20", "year": 2014 }, "ssbd": { "database": [], "repository": [] }, "title": "Dual catalysis with copper and rhenium for trifluoromethylation of propargylic alcohols: efficient synthesis of alpha-trifluoromethylated enones.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Using 11.7T ultra high-field T2-weighted MRI, the present study aimed to investigate pathological changes of primary and secondary trigeminal pathways following neonatal transection of infraorbital nerve in rats. The trigeminal pathways consist of spinal trigeminal tract, trigeminal sensory nuclear complex, medial lemniscus, ventromedial portion of external medullary lamina and ventral posterior nucleus of thalamus. By selecting optimum parameters of MRI such as repetition time, echo time, and slice orientation, this study visualized the trigeminal pathways in rats without any contrast agents. Pathological changes due to the nerve transection were found at 8 weeks of age as a marked reduction of the areas of the trigeminal pathways connecting from the injured nerve. In addition, T2-weighted MR images of the trigeminal nerve trunk and the spinal trigeminal tract suggest a communication of CSF through the trigeminal nerve between the inside and outside of the brain stem. These results support the utility of ultra high-field MRI system for noninvasive assessment of effects of trigeminal nerve injury upon the trigeminal pathways.", "classifications": [ { "id": "Suzuki", "label": "Group Suzuki", "parent": "Takekawa", "type": "group" }, { "id": "Takekawa", "label": "Team Takekawa", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yasuhiro", "last_name": "Ooi", "name": null }, { "creator_type": "author", "first_name": "Chizuko", "last_name": "Inui-Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Hiromichi", "last_name": "Nakadate", "name": null }, { "creator_type": "author", "first_name": "Yoshitaka", "last_name": "Nagase", "name": null }, { "creator_type": "author", "first_name": "Akitoshi", "last_name": "Seiyama", "name": null }, { "creator_type": "author", "first_name": "Yoshichika", "last_name": "Yoshioka", "name": null }, { "creator_type": "author", "first_name": "Junji", "last_name": "Seki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.brainres.2014.07.013" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "25038563" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Animals, Newborn", "descriptor_ui": "D000831", "major_topic": false }, { "descriptor": "Magnetic Resonance Imaging", "descriptor_ui": "D008279", "major_topic": true }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Maxillary Nerve", "descriptor_ui": "D008442", "major_topic": false }, { "descriptor": "Neural Pathways", "descriptor_ui": "D009434", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Rats, Wistar", "descriptor_ui": "D017208", "major_topic": false }, { "descriptor": "Thalamus", "descriptor_ui": "D013788", "major_topic": false }, { "descriptor": "Trigeminal Ganglion", "descriptor_ui": "D012668", "major_topic": false }, { "descriptor": "Trigeminal Nerve", "descriptor_ui": "D014276", "major_topic": false }, { "descriptor": "Trigeminal Nuclei", "descriptor_ui": "D014278", "major_topic": false } ], "publication": { "conference_name": null, "date": "2014 Sep 4", "date_precision": "day", "issue": "", "normalized_date": "2014-09-04", "pages": "84-92", "proceedings_title": null, "publisher": "", "title": "Brain research", "volume": "1579", "year": 2014 }, "ssbd": { "database": [], "repository": [] }, "title": "In vivo magnetic resonance imaging at 11.7 Tesla visualized the effects of neonatal transection of infraorbital nerve upon primary and secondary trigeminal pathways in rats.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Markers of cell cycle stage allow estimation of cell cycle dynamics in cell culture and during embryonic development. The Fucci system incorporates genetically encoded probes that highlight G1 and S/G2/M phases of the cell cycle allowing live imaging. However the available mouse models that incorporate Fucci are beset by problems with transgene inactivation, varying expression level, lack of conditional potential and/or the need to maintain separate transgenes—there is no transgenic mouse model that solves all these problems. To address these shortfalls we re-engineered the Fucci system to create 2 bicistronic Fucci variants incorporating both probes fused using the Thosea asigna virus 2A (T2A) self cleaving peptide. We characterize these variants in stable 3T3 cell lines. One of the variants (termed Fucci2a) faithfully recapitulated the nuclear localization and cell cycle stage specific florescence of the original Fucci system. We go on to develop a conditional mouse allele (R26Fucci2aR) carefully designed for high, inducible, ubiquitous expression allowing investigation of cell cycle status in single cell lineages within the developing embryo. We demonstrate the utility of R26Fucci2aR for live imaging by using high resolution confocal microscopy of ex vivo lung, kidney and neural crest development. Using our 3T3 system we describe and validate a method to estimate cell cycle times from relatively short time-lapse sequences that we then apply to our neural crest data. The Fucci2a system and the R26Fucci2aR mouse model are compelling new tools for the investigation of cell cycle dynamics in cell culture and during mouse embryonic development.", "classifications": [ { "id": "Sawano", "label": "Group Sawano", "parent": "Shintaku", "type": "group" }, { "id": "Shintaku", "label": "Team Shintaku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Richard Lester", "last_name": "Mort", "name": null }, { "creator_type": "author", "first_name": "Matthew Jonathan", "last_name": "Ford", "name": null }, { "creator_type": "author", "first_name": "Asako", "last_name": "Sakaue-Sawano", "name": null }, { "creator_type": "author", "first_name": "Nils Olof", "last_name": "Lindstrom", "name": null }, { "creator_type": "author", "first_name": "Angela", "last_name": "Casadio", "name": null }, { "creator_type": "author", "first_name": "Adam Thomas", "last_name": "Douglas", "name": null }, { "creator_type": "author", "first_name": "Margaret Anne", "last_name": "Keighren", "name": null }, { "creator_type": "author", "first_name": "Peter", "last_name": "Hohenstein", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Miyawaki", "name": null }, { "creator_type": "author", "first_name": "Ian James", "last_name": "Jackson", "name": null } ], "identifiers": { "doi": { "normalized": "10.4161/15384101.2015.945381" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "25486356" } }, "mesh": [ { "descriptor": "3T3 Cells", "descriptor_ui": "D016475", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Cycle", "descriptor_ui": "D002453", "major_topic": true }, { "descriptor": "Cell Proliferation", "descriptor_ui": "D049109", "major_topic": false }, { "descriptor": "Cell Survival", "descriptor_ui": "D002470", "major_topic": false }, { "descriptor": "Embryo, Mammalian", "descriptor_ui": "D004622", "major_topic": false }, { "descriptor": "Embryonic Stem Cells", "descriptor_ui": "D053595", "major_topic": false }, { "descriptor": "G1 Phase", "descriptor_ui": "D016193", "major_topic": false }, { "descriptor": "Gene Expression", "descriptor_ui": "D015870", "major_topic": true }, { "descriptor": "Genes, Reporter", "descriptor_ui": "D017930", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Integrases", "descriptor_ui": "D019426", "major_topic": false }, { "descriptor": "Kidney", "descriptor_ui": "D007668", "major_topic": false }, { "descriptor": "Luminescent Proteins", "descriptor_ui": "D008164", "major_topic": false }, { "descriptor": "Lung", "descriptor_ui": "D008168", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mitosis", "descriptor_ui": "D008938", "major_topic": false }, { "descriptor": "Morphogenesis", "descriptor_ui": "D009024", "major_topic": false }, { "descriptor": "Organ Specificity", "descriptor_ui": "D009928", "major_topic": true }, { "descriptor": "Red Fluorescent Protein", "descriptor_ui": "D000097573", "major_topic": false }, { "descriptor": "Time Factors", "descriptor_ui": "D013997", "major_topic": false }, { "descriptor": "Time-Lapse Imaging", "descriptor_ui": "D059008", "major_topic": false } ], "publication": { "conference_name": null, "date": "2014 Sep 1", "date_precision": "day", "issue": "17", "normalized_date": "2014-09-01", "pages": "2681-2696", "proceedings_title": null, "publisher": "", "title": "Cell Cycle", "volume": "13", "year": 2014 }, "ssbd": { "database": [], "repository": [] }, "title": "Fucci2a: A bicistronic cell cycle reporter that allows Cre mediated tissue specific expression in mice.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The structural dynamics of chromatin have been implicated in the regulation of fundamental eukaryotic processes, such as DNA transcription, replication and repair. Although previous studies have revealed that the chromatin landscape, nucleosome remodeling and histone modification events are intimately tied into cellular energetics and redox state, few studies undertake defined time-resolved measurements of these state variables. Here, we use metabolically synchronous, continuously-grown yeast cultures to measure DNA occupancy and track global patterns with respect to the metabolic state of the culture. Combined with transcriptome analyses and ChIP-qPCR experiments, these paint an intriguing picture where genome-wide nucleosome focusing occurs during the recovery of energy charge, followed by clearance of the promoter regions and global transcriptional slow-down, thus indicating a nucleosome-mediated \"reset point\" for the cycle. The reset begins at the end of the catabolic and stress-response transcriptional programs and ends prior to the start of the anabolic and cell-growth transcriptional program, and the histones on genes from both the catabolic and anabolic superclusters are deacetylated.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Cornelia", "last_name": "Amariei", "name": null }, { "creator_type": "author", "first_name": "Rainer", "last_name": "Machne", "name": null }, { "creator_type": "author", "first_name": "Viktor", "last_name": "Stolc", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Masaru", "last_name": "Tomita", "name": null }, { "creator_type": "author", "first_name": "Douglas B.", "last_name": "Murray", "name": null } ], "identifiers": { "doi": { "normalized": "10.15698/mic2014.09.166" }, "pmcid": { "normalized": "PMC5349131" }, "pmid": { "normalized": "28357254" } }, "mesh": [], "publication": { "conference_name": null, "date": "2014 Sep 1", "date_precision": "day", "issue": "9", "normalized_date": "2014-09-01", "pages": "279-288", "proceedings_title": null, "publisher": "", "title": "Microbial cell (Graz, Austria)", "volume": "1", "year": 2014 }, "ssbd": { "database": [], "repository": [] }, "title": "Time resolved DNA occupancy dynamics during the respiratory oscillation uncover a global reset point in the yeast growth program.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The formation of vascular structures requires precisely controlled proliferation of endothelial cells (ECs), which occurs through strict regulation of the cell cycle. However, the mechanism by which EC proliferation is coordinated during vascular formation remains largely unknown, since a method of analyzing cell-cycle progression of ECs in living animals has been lacking. Thus, we devised a novel system allowing the cell-cycle progression of ECs to be visualized in vivo. To achieve this aim, we generated a transgenic zebrafish line that expresses zFucci (zebrafish fluorescent ubiquitination-based cell cycle indicator) specifically in ECs (an EC-zFucci Tg line). We first assessed whether this system works by labeling the S phase ECs with EdU, then performing time-lapse imaging analyses and, finally, examining the effects of cell-cycle inhibitors. Employing the EC-zFucci Tg line, we analyzed the cell-cycle progression of ECs during vascular development in different regions and at different time points and found that ECs proliferate actively in the developing vasculature. The proliferation of ECs also contributes to the elongation of newly formed blood vessels. While ECs divide during elongation in intersegmental vessels, ECs proliferate in the primordial hindbrain channel to serve as an EC reservoir and migrate into basilar and central arteries, thereby contributing to new blood vessel formation. Furthermore, while EC proliferation is not essential for the formation of the basic framework structures of intersegmental and caudal vessels, it appears to be required for full maturation of these vessels. In addition, venous ECs mainly proliferate in the late stage of vascular development, whereas arterial ECs become quiescent at this stage. Thus, we anticipate that the EC-zFucci Tg line can serve as a tool for detailed studies of the proliferation of ECs in various forms of vascular development in vivo.", "classifications": [ { "id": "Sawano", "label": "Group Sawano", "parent": "Shintaku", "type": "group" }, { "id": "Shintaku", "label": "Team Shintaku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Shigetomo", "last_name": "Fukuhara", "name": null }, { "creator_type": "author", "first_name": "Jianghui", "last_name": "Zhang", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Yuge", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Ando", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Wakayama", "name": null }, { "creator_type": "author", "first_name": "Asako", "last_name": "Sakaue-Sawano", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Miyawaki", "name": null }, { "creator_type": "author", "first_name": "Naoki", "last_name": "Mochizuki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.ydbio.2014.06.015" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "24975012" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Animals, Genetically Modified", "descriptor_ui": "D030801", "major_topic": false }, { "descriptor": "Cell Cycle", "descriptor_ui": "D002453", "major_topic": false }, { "descriptor": "Cell Division", "descriptor_ui": "D002455", "major_topic": false }, { "descriptor": "Cell Proliferation", "descriptor_ui": "D049109", "major_topic": false }, { "descriptor": "Cyclin-Dependent Kinase Inhibitor p27", "descriptor_ui": "D050760", "major_topic": false }, { "descriptor": "Endothelium, Vascular", "descriptor_ui": "D004730", "major_topic": false }, { "descriptor": "Gene Knockdown Techniques", "descriptor_ui": "D055785", "major_topic": false }, { "descriptor": "Intracellular Signaling Peptides and Proteins", "descriptor_ui": "D047908", "major_topic": false }, { "descriptor": "Membrane Proteins", "descriptor_ui": "D008565", "major_topic": false }, { "descriptor": "Morpholinos", "descriptor_ui": "D060172", "major_topic": false }, { "descriptor": "Neovascularization, Physiologic", "descriptor_ui": "D018919", "major_topic": false }, { "descriptor": "Zebrafish", "descriptor_ui": "D015027", "major_topic": false }, { "descriptor": "Zebrafish Proteins", "descriptor_ui": "D029961", "major_topic": false } ], "publication": { "conference_name": null, "date": "2014 Sep 1", "date_precision": "day", "issue": "1", "normalized_date": "2014-09-01", "pages": "10-23", "proceedings_title": null, "publisher": "", "title": "Developmental biology", "volume": "393", "year": 2014 }, "ssbd": { "database": [], "repository": [] }, "title": "Visualizing the cell-cycle progression of endothelial cells in zebrafish.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Cellular homeostasis is regulated by signals through multiple molecular networks that include protein phosphorylation and metabolites. However, where and when the signal flows through a network and regulates homeostasis has not been explored. We have developed a reconstruction method for the signal flow based on time-course phosphoproteome and metabolome data, using multiple databases, and have applied it to acute action of insulin, an important hormone for metabolic homeostasis. An insulin signal flows through a network, through signaling pathways that involve 13 protein kinases, 26 phosphorylated metabolic enzymes, and 35 allosteric effectors, resulting in quantitative changes in 44 metabolites. Analysis of the network reveals that insulin induces phosphorylation and activation of liver-type phosphofructokinase 1, thereby controlling a key reaction in glycolysis. We thus provide a versatile method of reconstruction of signal flow through the network using phosphoproteome and metabolome data.", "classifications": [ { "id": "Kuroda", "label": "Group Kuroda", "parent": "Kuroda", "type": "group" }, { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Katsuyuki", "last_name": "Yugi", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Kubota", "name": null }, { "creator_type": "author", "first_name": "Yu", "last_name": "Toyoshima", "name": null }, { "creator_type": "author", "first_name": "Rei", "last_name": "Noguchi", "name": null }, { "creator_type": "author", "first_name": "Kentaro", "last_name": "Kawata", "name": null }, { "creator_type": "author", "first_name": "Yasunori", "last_name": "Komori", "name": null }, { "creator_type": "author", "first_name": "Shinsuke", "last_name": "Uda", "name": null }, { "creator_type": "author", "first_name": "Katsuyuki", "last_name": "Kunida", "name": null }, { "creator_type": "author", "first_name": "Yoko", "last_name": "Tomizawa", "name": null }, { "creator_type": "author", "first_name": "Yosuke", "last_name": "Funato", "name": null }, { "creator_type": "author", "first_name": "Hiroaki", "last_name": "Miki", "name": null }, { "creator_type": "author", "first_name": "Masaki", "last_name": "Matsumoto", "name": null }, { "creator_type": "author", "first_name": "Keiichi I.", "last_name": "Nakayama", "name": null }, { "creator_type": "author", "first_name": "Kasumi", "last_name": "Kashikura", "name": null }, { "creator_type": "author", "first_name": "Keiko", "last_name": "Endo", "name": null }, { "creator_type": "author", "first_name": "Kazutaka", "last_name": "Ikeda", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Kuroda", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.celrep.2014.07.021" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "25131207" } }, "mesh": [ { "descriptor": "Allosteric Regulation", "descriptor_ui": "D000494", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "HEK293 Cells", "descriptor_ui": "D057809", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Insulin", "descriptor_ui": "D007328", "major_topic": false }, { "descriptor": "Metabolic Networks and Pathways", "descriptor_ui": "D053858", "major_topic": false }, { "descriptor": "Metabolome", "descriptor_ui": "D055442", "major_topic": false }, { "descriptor": "Phosphoproteins", "descriptor_ui": "D010750", "major_topic": false }, { "descriptor": "Phosphorylation", "descriptor_ui": "D010766", "major_topic": false }, { "descriptor": "Protein Processing, Post-Translational", "descriptor_ui": "D011499", "major_topic": true }, { "descriptor": "Proteome", "descriptor_ui": "D020543", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false } ], "publication": { "conference_name": null, "date": "2014 Aug 21", "date_precision": "day", "issue": "4", "normalized_date": "2014-08-21", "pages": "1171-1183", "proceedings_title": null, "publisher": "", "title": "Cell reports", "volume": "8", "year": 2014 }, "ssbd": { "database": [], "repository": [] }, "title": "Reconstruction of insulin signal flow from phosphoproteome and metabolome data.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Skeletal muscle stem cells (MuSCs), the major source for skeletal muscle regeneration in vertebrates, are in a state of cell cycle arrest in adult skeletal muscles. Prior evidence suggests that embryonic muscle progenitors proliferate and differentiate to form myofibres and also self-renew, implying that MuSCs, derived from these cells, acquire quiescence later during development. Depletion of Dicer in adult MuSCs promoted their exit from quiescence, suggesting microRNAs are involved in the maintenance of quiescence. Here we identified miR-195 and miR-497 that induce cell cycle arrest by targeting cell cycle genes, Cdc25 and Ccnd. Reduced expression of MyoD in juvenile MuSCs, as a result of overexpressed miR-195/497 or attenuated Cdc25/Ccnd, revealed an intimate link between quiescence and suppression of myogenesis in MuSCs. Transplantation of cultured MuSCs treated with miR-195/497 contributed more efficiently to regenerating muscles of dystrophin-deficient mice, indicating the potential utility of miR-195/497 for stem cell therapies.", "classifications": [ { "id": "Yamamoto", "label": "Group Yamamoto", "parent": "Toyoshima", "type": "group" }, { "id": "Toyoshima", "label": "Team Toyoshima", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Takahiko", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Atsuko", "last_name": "Sehara-Fujisawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/ncomms5597" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "25119651" } }, "mesh": [ { "descriptor": "Aging", "descriptor_ui": "D000375", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "cdc25 Phosphatases", "descriptor_ui": "D020687", "major_topic": false }, { "descriptor": "Cell Cycle", "descriptor_ui": "D002453", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred Strains", "descriptor_ui": "D008815", "major_topic": false }, { "descriptor": "MicroRNAs", "descriptor_ui": "D035683", "major_topic": false }, { "descriptor": "Morphogenesis", "descriptor_ui": "D009024", "major_topic": false }, { "descriptor": "Muscle Development", "descriptor_ui": "D024510", "major_topic": false }, { "descriptor": "Muscle, Skeletal", "descriptor_ui": "D018482", "major_topic": false }, { "descriptor": "MyoD Protein", "descriptor_ui": "D017570", "major_topic": false }, { "descriptor": "Stem Cells", "descriptor_ui": "D013234", "major_topic": false } ], "publication": { "conference_name": null, "date": "2014 Aug 14", "date_precision": "day", "issue": "", "normalized_date": "2014-08-14", "pages": "4597", "proceedings_title": null, "publisher": "", "title": "Nature communications", "volume": "5", "year": 2014 }, "ssbd": { "database": [], "repository": [] }, "title": "miR-195/497 induce postnatal quiescence of skeletal muscle stem cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The trifluoromethyl group is found in many synthetic bioactive compounds, and the difunctionalization of a C=C bond, as a powerful strategy for the construction of compounds with various functional groups, has been intensively investigated. Therefore, the difunctionalizing trifluoromethylation of alkenes has attracted growing interest because of the potential of the products as building blocks for bioactive molecules. In this review, we focus on recent advances in the trifluoromethylation of alkenes with concomitant introduction of additional functional groups.", "classifications": [ { "id": "Sodeoka", "label": "Group Sodeoka", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Hiromichi", "last_name": "Egami", "name": null }, { "creator_type": "author", "first_name": "Mikiko", "last_name": "Sodeoka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/anie.201309260" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "24961669" } }, "mesh": [ { "descriptor": "Alkenes", "descriptor_ui": "D000475", "major_topic": false }, { "descriptor": "Catalysis", "descriptor_ui": "D002384", "major_topic": false }, { "descriptor": "Methylation", "descriptor_ui": "D008745", "major_topic": true }, { "descriptor": "Molecular Structure", "descriptor_ui": "D015394", "major_topic": false } ], "publication": { "conference_name": null, "date": "2014 Aug 4", "date_precision": "day", "issue": "32", "normalized_date": "2014-08-04", "pages": "8294-8308", "proceedings_title": null, "publisher": "", "title": "Angewandte Chemie (International ed. in English)", "volume": "53", "year": 2014 }, "ssbd": { "database": [], "repository": [] }, "title": "Trifluoromethylation of alkenes with concomitant introduction of additional functional groups.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Vein formation is an important process in plant leaf development. The phytohormone auxin is known as the most important molecule for the control of venation patterning; and the canalization model, in which cells experiencing higher auxin flux differentiate into specific cells for auxin transportation, is widely accepted. To date, several mathematical models based on the canalization hypothesis have been proposed that have succeeded in reproducing vein patterns similar to those observed in actual leaves. However, most previous studies focused on patterning in fixed domains, and, in a few exceptional studies, limited tissue growth - such as cell proliferation at leaf margins and small deformations without large changes in cell number - were dealt with. Considering that, in actual leaf development, venation patterning occurs in an exponentially growing tissue, whether the canalization hypothesis still applies is an important issue to be addressed. In this study, we first show through a pilot simulation that the coupling of chemical dynamics for canalization and tissue growth as independent models cannot reproduce normal venation patterning. We then examine conditions sufficient for achieving normal patterning in a growing leaf by introducing various constraints on chemical dynamics, tissue growth, and cell mechanics; in doing so, we found that auxin flux- or differentiation-dependent modification of the cell cycle and elasticity of cell edges are essential. The predictions given by our simulation study will serve as guideposts in experiments aimed at finding the key factors for achieving normal venation patterning in developing plant leaves.", "classifications": [ { "id": "Morishita", "label": "Group Morishita", "parent": "Morishita", "type": "group" }, { "id": "Morishita", "label": "Team Morishita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Sang-Woo", "last_name": "Lee", "name": null }, { "creator_type": "author", "first_name": "Francois Gabriel", "last_name": "Feugier", "name": null }, { "creator_type": "author", "first_name": "Yoshihiro", "last_name": "Morishita", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.jtbi.2014.03.005" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "24632445" } }, "mesh": [ { "descriptor": "Arabidopsis", "descriptor_ui": "D017360", "major_topic": false }, { "descriptor": "Cell Cycle", "descriptor_ui": "D002453", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Cell Division", "descriptor_ui": "D002455", "major_topic": false }, { "descriptor": "Computer Simulation", "descriptor_ui": "D003198", "major_topic": false }, { "descriptor": "Indoleacetic Acids", "descriptor_ui": "D007210", "major_topic": false }, { "descriptor": "Models, Biological", "descriptor_ui": "D008954", "major_topic": false }, { "descriptor": "Numerical Analysis, Computer-Assisted", "descriptor_ui": "D009716", "major_topic": false }, { "descriptor": "Organogenesis", "descriptor_ui": "D038081", "major_topic": false }, { "descriptor": "Plant Vascular Bundle", "descriptor_ui": "D058526", "major_topic": false }, { "descriptor": "Time Factors", "descriptor_ui": "D013997", "major_topic": false } ], "publication": { "conference_name": null, "date": "2014 Jul 21", "date_precision": "day", "issue": "", "normalized_date": "2014-07-21", "pages": "104-120", "proceedings_title": null, "publisher": "", "title": "Journal of theoretical biology", "volume": "353", "year": 2014 }, "ssbd": { "database": [], "repository": [] }, "title": "Canalization-based vein formation in a growing leaf.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "We demonstrate dynamic surface-enhanced Raman scattering (SERS) imaging with 3 dimensional mapping in a living cell by combining a confocal Raman spectrometer and dual-focus dark-field microscopy. Gold nanoparticles acting as a probe traveling through the living cell, are tracked by dual-focus dark-field imaging, with position feedback to the confocal Raman spectrometer in order to record evolving SERS signals from the same gold nanoparticle moving through the cell. Simultaneous detection of motion and the SERS spectrum enables the visualization of the SERS pathways. Observation of how the SERS spectra change in space and time during biological functions or by changes of the molecular environment provides exciting opportunities for understanding the molecular basis of the cell dynamics.", "classifications": [ { "id": "Fujita", "label": "Group Fujita", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Kai-Chih", "last_name": "Huang", "name": null }, { "creator_type": "author", "first_name": "Kazuki", "last_name": "Bando", "name": null }, { "creator_type": "author", "first_name": "Jun", "last_name": "Ando", "name": null }, { "creator_type": "author", "first_name": "Nicholas I.", "last_name": "Smith", "name": null }, { "creator_type": "author", "first_name": "Katsumasa", "last_name": "Fujita", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Kawata", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.ymeth.2014.02.007" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "24556553" } }, "mesh": [ { "descriptor": "Biological Transport", "descriptor_ui": "D001692", "major_topic": false }, { "descriptor": "Cell Tracking", "descriptor_ui": "D058948", "major_topic": false }, { "descriptor": "Cytoplasm", "descriptor_ui": "D003593", "major_topic": false }, { "descriptor": "Gold", "descriptor_ui": "D006046", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Imaging, Three-Dimensional", "descriptor_ui": "D021621", "major_topic": false }, { "descriptor": "Metal Nanoparticles", "descriptor_ui": "D053768", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": true }, { "descriptor": "Spectrum Analysis, Raman", "descriptor_ui": "D013059", "major_topic": false }, { "descriptor": "Surface Plasmon Resonance", "descriptor_ui": "D020349", "major_topic": false } ], "publication": { "conference_name": null, "date": "2014 Jul 1", "date_precision": "day", "issue": "2", "normalized_date": "2014-07-01", "pages": "348-353", "proceedings_title": null, "publisher": "", "title": "Methods (San Diego, Calif.)", "volume": "68", "year": 2014 }, "ssbd": { "database": [], "repository": [] }, "title": "3D SERS (surface enhanced Raman scattering) imaging of intracellular pathways.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The development of new and mild protocols for the specific enrichment of biomolecules is of significant interest from the perspective of chemical biology. A cobalt-phosphine complex immobilised on a solid-phase resin has been found to selectively bind to a propargyl carbamate tag, that is, \"catch\", under dilute aqueous conditions (pH 7) at 4 degrees C. Upon acidic treatment of the resulting resin-bound alkyne-cobalt complex, the Nicholas reaction was induced to \"release\" the alkyne-tagged molecule from the resin as a free amine. Model studies revealed that selective enrichment of the alkyne-tagged molecule could be achieved with high efficiency at 4 degrees C. The proof-of-concept was applied to an alkyne-tagged amino acid and dipeptide. Studies using an alkyne-tagged dipeptide proved that this protocol is compatible with various amino acids bearing a range of functionalities in the side-chain. In addition, selective enrichment and detection of an amine derived from the \"catch and release\" of an alkyne-tagged dipeptide in the presence of various peptides has been accomplished under highly dilute conditions, as determined by mass spectrometry.", "classifications": [ { "id": "Sodeoka", "label": "Group Sodeoka", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Ayako", "last_name": "Miyazaki", "name": null }, { "creator_type": "author", "first_name": "Miwako", "last_name": "Asanuma", "name": null }, { "creator_type": "author", "first_name": "Kosuke", "last_name": "Dodo", "name": null }, { "creator_type": "author", "first_name": "Hiromichi", "last_name": "Egami", "name": null }, { "creator_type": "author", "first_name": "Mikiko", "last_name": "Sodeoka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/chem.201400056" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "24788842" } }, "mesh": [ { "descriptor": "Alkynes", "descriptor_ui": "D000480", "major_topic": false }, { "descriptor": "Cobalt", "descriptor_ui": "D003035", "major_topic": false }, { "descriptor": "Molecular Structure", "descriptor_ui": "D015394", "major_topic": false }, { "descriptor": "Peptides", "descriptor_ui": "D010455", "major_topic": false } ], "publication": { "conference_name": null, "date": "2014 Jun 23", "date_precision": "day", "issue": "26", "normalized_date": "2014-06-23", "pages": "8116-8128", "proceedings_title": null, "publisher": "", "title": "Chemistry (Weinheim an der Bergstrasse, Germany)", "volume": "20", "year": 2014 }, "ssbd": { "database": [], "repository": [] }, "title": "A \"catch-and-release\" protocol for alkyne-tagged molecules based on a resin-bound cobalt complex for peptide enrichment in aqueous media.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Using methodology developed herein, it is found that reactive persulfides and polysulfides are formed endogenously from both small molecule species and proteins in high amounts in mammalian cells and tissues. These reactive sulfur species were biosynthesized by two major sulfurtransferases: cystathionine beta-synthase and cystathionine gamma-lyase. Quantitation of these species indicates that high concentrations of glutathione persulfide (perhydropersulfide >100 muM) and other cysteine persulfide and polysulfide derivatives in peptides/proteins were endogenously produced and maintained in the plasma, cells, and tissues of mammals (rodent and human). It is expected that persulfides are especially nucleophilic and reducing. This view was found to be the case, because they quickly react with H2O2 and a recently described biologically generated electrophile 8-nitroguanosine 3',5'-cyclic monophosphate. These results indicate that persulfides are potentially important signaling/effector species, and because H2S can be generated from persulfide degradation, much of the reported biological activity associated with H2S may actually be that of persulfides. That is, H2S may act primarily as a marker for the biologically active of persulfide species.", "classifications": [ { "id": "Akaike", "label": "Group Akaike", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Tomoaki", "last_name": "Ida", "name": null }, { "creator_type": "author", "first_name": "Tomohiro", "last_name": "Sawa", "name": null }, { "creator_type": "author", "first_name": "Hideshi", "last_name": "Ihara", "name": null }, { "creator_type": "author", "first_name": "Yukihiro", "last_name": "Tsuchiya", "name": null }, { "creator_type": "author", "first_name": "Yasuo", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Yoshito", "last_name": "Kumagai", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Suematsu", "name": null }, { "creator_type": "author", "first_name": "Hozumi", "last_name": "Motohashi", "name": null }, { "creator_type": "author", "first_name": "Shigemoto", "last_name": "Fujii", "name": null }, { "creator_type": "author", "first_name": "Tetsuro", "last_name": "Matsunaga", "name": null }, { "creator_type": "author", "first_name": "Masayuki", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Katsuhiko", "last_name": "Ono", "name": null }, { "creator_type": "author", "first_name": "Nelmi O.", "last_name": "Devarie-Baez", "name": null }, { "creator_type": "author", "first_name": "Ming", "last_name": "Xian", "name": null }, { "creator_type": "author", "first_name": "Jon M.", "last_name": "Fukuto", "name": null }, { "creator_type": "author", "first_name": "Takaaki", "last_name": "Akaike", "name": null } ], "identifiers": { "doi": { "normalized": "10.1073/pnas.1321232111" }, "pmcid": { "normalized": "PMC4040604" }, "pmid": { "normalized": "24733942" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Chromatography, Liquid", "descriptor_ui": "D002853", "major_topic": false }, { "descriptor": "Cyclic GMP", "descriptor_ui": "D006152", "major_topic": false }, { "descriptor": "Cystathionine beta-Synthase", "descriptor_ui": "D003541", "major_topic": false }, { "descriptor": "Cystathionine gamma-Lyase", "descriptor_ui": "D003542", "major_topic": false }, { "descriptor": "Cysteine", "descriptor_ui": "D003545", "major_topic": false }, { "descriptor": "Disulfides", "descriptor_ui": "D004220", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Hydrogen Peroxide", "descriptor_ui": "D006861", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Oxidation-Reduction", "descriptor_ui": "D010084", "major_topic": false }, { "descriptor": "Oxidative Stress", "descriptor_ui": "D018384", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Sulfhydryl Compounds", "descriptor_ui": "D013438", "major_topic": false }, { "descriptor": "Tandem Mass Spectrometry", "descriptor_ui": "D053719", "major_topic": false } ], "publication": { "conference_name": null, "date": "2014 May 27", "date_precision": "day", "issue": "21", "normalized_date": "2014-05-27", "pages": "7606-7611", "proceedings_title": null, "publisher": "", "title": "Proceedings of the National Academy of Sciences of the United States of America", "volume": "111", "year": 2014 }, "ssbd": { "database": [], "repository": [] }, "title": "Reactive cysteine persulfides and S-polythiolation regulate oxidative stress and redox signaling.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Sterile inflammation triggered by endogenous factors is thought to contribute to the pathogenesis of acute and chronic inflammatory diseases. Here, we demonstrate that apoptosis-deficient mutants spontaneously develop a necrosis-driven systemic immune response in Drosophila and provide an in vivo model for studying the organismal response to sterile inflammation. Metabolomic analysis of hemolymph from apoptosis-deficient mutants revealed increased sarcosine and reduced S-adenosyl-methionine (SAM) levels due to glycine N-methyltransferase (Gnmt) upregulation. We showed that Gnmt was elevated in response to Toll activation induced by the local necrosis of wing epidermal cells. Necrosis-driven inflammatory conditions induced dFoxO hyperactivation, leading to an energy-wasting phenotype. Gnmt was cell-autonomously upregulated by dFoxO in the fat body as a possible rheostat for controlling energy loss, which functioned during fasting as well as inflammatory conditions. We propose that the dFoxO-Gnmt axis is essential for the maintenance of organismal SAM metabolism and energy homeostasis.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Fumiaki", "last_name": "Obata", "name": null }, { "creator_type": "author", "first_name": "Erina", "last_name": "Kuranaga", "name": null }, { "creator_type": "author", "first_name": "Katsura", "last_name": "Tomioka", "name": null }, { "creator_type": "author", "first_name": "Ming", "last_name": "Ming", "name": null }, { "creator_type": "author", "first_name": "Asuka", "last_name": "Takeishi", "name": null }, { "creator_type": "author", "first_name": "Chun-Hong", "last_name": "Chen", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Masayuki", "last_name": "Miura", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.celrep.2014.03.046" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "24746817" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Apoptosis", "descriptor_ui": "D017209", "major_topic": false }, { "descriptor": "DNA Methylation", "descriptor_ui": "D019175", "major_topic": false }, { "descriptor": "Drosophila", "descriptor_ui": "D004330", "major_topic": false }, { "descriptor": "Drosophila Proteins", "descriptor_ui": "D029721", "major_topic": false }, { "descriptor": "Energy Metabolism", "descriptor_ui": "D004734", "major_topic": false }, { "descriptor": "Forkhead Transcription Factors", "descriptor_ui": "D051858", "major_topic": false }, { "descriptor": "Glycine N-Methyltransferase", "descriptor_ui": "D050938", "major_topic": false }, { "descriptor": "Immune System", "descriptor_ui": "D007107", "major_topic": false }, { "descriptor": "Metabolome", "descriptor_ui": "D055442", "major_topic": false }, { "descriptor": "Necrosis", "descriptor_ui": "D009336", "major_topic": true }, { "descriptor": "Phenotype", "descriptor_ui": "D010641", "major_topic": false }, { "descriptor": "S-Adenosylmethionine", "descriptor_ui": "D012436", "major_topic": false }, { "descriptor": "Sarcosine", "descriptor_ui": "D012521", "major_topic": false }, { "descriptor": "Up-Regulation", "descriptor_ui": "D015854", "major_topic": false } ], "publication": { "conference_name": null, "date": "2014 May 8", "date_precision": "day", "issue": "3", "normalized_date": "2014-05-08", "pages": "821-833", "proceedings_title": null, "publisher": "", "title": "Cell reports", "volume": "7", "year": 2014 }, "ssbd": { "database": [], "repository": [] }, "title": "Necrosis-driven systemic immune response alters SAM metabolism through the FOXO-GNMT axis.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "In this article, we show that mouse embryonic stem cell- or induced pluripotent stem cell-derived 3D retinal tissue developed a structured outer nuclear layer (ONL) with complete inner and outer segments even in an advanced retinal degeneration model (rd1) that lacked ONL. We also observed host-graft synaptic connections by immunohistochemistry. This study provides a \"proof of concept\" for retinal sheet transplantation therapy for advanced retinal degenerative diseases.", "classifications": [ { "id": "Eiraku", "label": "Group Eiraku", "parent": "Eiraku", "type": "group" }, { "id": "Eiraku", "label": "Team Eiraku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Juthaporn", "last_name": "Assawachananont", "name": null }, { "creator_type": "author", "first_name": "Michiko", "last_name": "Mandai", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Okamoto", "name": null }, { "creator_type": "author", "first_name": "Chikako", "last_name": "Yamada", "name": null }, { "creator_type": "author", "first_name": "Mototsugu", "last_name": "Eiraku", "name": null }, { "creator_type": "author", "first_name": "Shigenobu", "last_name": "Yonemura", "name": null }, { "creator_type": "author", "first_name": "Yoshiki", "last_name": "Sasai", "name": null }, { "creator_type": "author", "first_name": "Masayo", "last_name": "Takahashi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.stemcr.2014.03.011" }, "pmcid": { "normalized": "PMC4050483" }, "pmid": { "normalized": "24936453" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Culture Techniques", "descriptor_ui": "D018929", "major_topic": false }, { "descriptor": "Collagen", "descriptor_ui": "D003094", "major_topic": false }, { "descriptor": "Drug Combinations", "descriptor_ui": "D004338", "major_topic": false }, { "descriptor": "Embryonic Stem Cells", "descriptor_ui": "D053595", "major_topic": false }, { "descriptor": "Immunohistochemistry", "descriptor_ui": "D007150", "major_topic": false }, { "descriptor": "Induced Pluripotent Stem Cells", "descriptor_ui": "D057026", "major_topic": false }, { "descriptor": "Laminin", "descriptor_ui": "D007797", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C3H", "descriptor_ui": "D008809", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mitochondria", "descriptor_ui": "D008928", "major_topic": false }, { "descriptor": "Proteoglycans", "descriptor_ui": "D011509", "major_topic": false }, { "descriptor": "Receptors, Retinoic Acid", "descriptor_ui": "D018168", "major_topic": false }, { "descriptor": "Retina", "descriptor_ui": "D012160", "major_topic": false }, { "descriptor": "Retinal Degeneration", "descriptor_ui": "D012162", "major_topic": false }, { "descriptor": "Transplantation, Homologous", "descriptor_ui": "D014184", "major_topic": false } ], "publication": { "conference_name": null, "date": "2014 May 6", "date_precision": "day", "issue": "5", "normalized_date": "2014-05-06", "pages": "662-674", "proceedings_title": null, "publisher": "", "title": "Stem cell reports", "volume": "2", "year": 2014 }, "ssbd": { "database": [ "ssbd-database-000028" ], "repository": [ "ssbd-repos-000028" ] }, "title": "Transplantation of embryonic and induced pluripotent stem cell-derived 3D retinal sheets into retinal degenerative mice.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The identity and behavior of mouse spermatogenic stem cells have been a long-standing focus of interest. In the prevailing \"As model,\" stem cell function is restricted to singly isolated (As) spermatogonia. By examining single-cell dynamics of GFRalpha1+ stem cells in vivo, we evaluate an alternative hypothesis that, through fragmentation, syncytial spermatogonia also contribute to stem cell function in homeostasis. We use live imaging and pulse labeling to quantitatively determine the fates of individual GFRalpha1+ cells and find that, during steady-state spermatogenesis, the entire GFRalpha1+ population comprises a single stem cell pool, in which cells continually interconvert between As and syncytial states. A minimal biophysical model, relying only on the rates of incomplete cell division and syncytial fragmentation, precisely predicts the stochastic fates of GFRalpha1+ cells during steady state and postinsult regeneration. Thus, our results define an alternative and dynamic model for spermatogenic stem cell function in the mouse testis.", "classifications": [ { "id": "Enomoto", "label": "Group Enomoto", "parent": "Enomoto", "type": "group" }, { "id": "Enomoto", "label": "Team Enomoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Kenshiro", "last_name": "Hara", "name": null }, { "creator_type": "author", "first_name": "Toshinori", "last_name": "Nakagawa", "name": null }, { "creator_type": "author", "first_name": "Hideki", "last_name": "Enomoto", "name": null }, { "creator_type": "author", "first_name": "Mikiko", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Masayuki", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Benjamin D.", "last_name": "Simons", "name": null }, { "creator_type": "author", "first_name": "Shosei", "last_name": "Yoshida", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.stem.2014.01.019" }, "pmcid": { "normalized": "PMC4010676" }, "pmid": { "normalized": "24792118" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Glial Cell Line-Derived Neurotrophic Factor Receptors", "descriptor_ui": "D051097", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Spermatogenesis", "descriptor_ui": "D013091", "major_topic": false }, { "descriptor": "Stem Cells", "descriptor_ui": "D013234", "major_topic": false } ], "publication": { "conference_name": null, "date": "2014 May 1", "date_precision": "day", "issue": "5", "normalized_date": "2014-05-01", "pages": "658-672", "proceedings_title": null, "publisher": "", "title": "Cell stem cell", "volume": "14", "year": 2014 }, "ssbd": { "database": [], "repository": [] }, "title": "Mouse spermatogenic stem cells continually interconvert between equipotent singly isolated and syncytial states.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Intracellular Ca(2+) ([Ca(2+)]i) dynamics in isolated myocytes differ between the atria and ventricles due to the distinct t-tubular distributions. Although cellular aspects of ventricular [Ca(2+)]i dynamics in the heart have been extensively studied, little is known about those of atrial myocytes in situ. Here we visualized precise [Ca(2+)]i dynamics of atrial myocytes in Langendorff-perfused rat hearts by rapid-scanning confocal microscopy. Of 16 fluo-4-loaded hearts imaged during pacing up to 4-Hz, five hearts showed spatially uniform Ca(2+) transients on systole among individual cells, whereas no discernible [Ca(2+)]i elevation developed during diastole. In contrast, the remaining hearts showed non-uniform [Ca(2+)]i dynamics within and among the cells especially under high-frequency (4 Hz) excitation, where subcellular cluster-like [Ca(2+)]i rises or wave-like [Ca(2+)]i propagation occurred on excitation. Such [Ca(2+)]i inhomogeneity was more pronounced at high-frequency pacing, showing beat-to-beat Ca(2+) transient alternans. Despite such non-uniform dynamics, cessation of burst pacing of the atria was not followed by emergence of spontaneous Ca(2+) waves, indicating minor Ca(2+)-releasing potentials of the sarcoplasmic reticulum (SR). In summary, rat atria display a propensity to show non-uniform [Ca(2+)]i dynamics on systole due to impaired Ca(2+)-release from the SR and paucity of t-tubules. Our results provide an important basis for understanding atrial pathophysiology.", "classifications": [ { "id": "Tanaka", "label": "Group Tanaka", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yan", "last_name": "Jiang", "name": null }, { "creator_type": "author", "first_name": "Hideo", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Taka-Aki", "last_name": "Matsuyama", "name": null }, { "creator_type": "author", "first_name": "Yoshihisa", "last_name": "Yamaoka", "name": null }, { "creator_type": "author", "first_name": "Tetsuro", "last_name": "Takamatsu", "name": null } ], "identifiers": { "doi": { "normalized": "10.1267/ahc.14014" }, "pmcid": { "normalized": "PMC4138402" }, "pmid": { "normalized": "25221364" } }, "mesh": [], "publication": { "conference_name": null, "date": "2014 May 1", "date_precision": "day", "issue": "2", "normalized_date": "2014-05-01", "pages": "59-65", "proceedings_title": null, "publisher": "", "title": "Acta histochemica et cytochemica", "volume": "47", "year": 2014 }, "ssbd": { "database": [], "repository": [] }, "title": "Pacing-induced non-uniform ca(2+) dynamics in rat atria revealed by rapid-scanning confocal microscopy.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "New derivatives of Vaccinia H1-related phosphatase (VHR) inhibitor RE12 (5) were designed by replacing the long straight alkyl chain with other hydrophobic functionalities containing two aromatic rings, with the aim of obtaining potent, cell-active inhibitors. We established a direct coupling reaction between tetronic acid derivative and thioimidate to prepare the RE derivatives 6a-6i efficiently. These compounds all showed VHR-inhibitory activity in the presence of 0.001% NP-40, whereas RE12 (5) was inactive under this condition, even at 100 muM. Further structure-activity studies focused on terminal substitution afforded trifluoromethyl derivative 6k (RE176) and nitro derivative 6l (RE177). The IC50 value of 6l in the presence of NP-40 was almost equivalent to that of RE12 (5) in its absence. Compound 6k (RE176) potently inhibited proliferation of HeLa cells.", "classifications": [ { "id": "Sodeoka", "label": "Group Sodeoka", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Frederic", "last_name": "Thuaud", "name": null }, { "creator_type": "author", "first_name": "Shuntaro", "last_name": "Kojima", "name": null }, { "creator_type": "author", "first_name": "Go", "last_name": "Hirai", "name": null }, { "creator_type": "author", "first_name": "Kana", "last_name": "Oonuma", "name": null }, { "creator_type": "author", "first_name": "Ayako", "last_name": "Tsuchiya", "name": null }, { "creator_type": "author", "first_name": "Takako", "last_name": "Uchida", "name": null }, { "creator_type": "author", "first_name": "Teruhisa", "last_name": "Tsuchimoto", "name": null }, { "creator_type": "author", "first_name": "Mikiko", "last_name": "Sodeoka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.bmc.2014.03.012" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "24702858" } }, "mesh": [ { "descriptor": "4-Butyrolactone", "descriptor_ui": "D015107", "major_topic": false }, { "descriptor": "Benzylamines", "descriptor_ui": "D001596", "major_topic": false }, { "descriptor": "Cell Proliferation", "descriptor_ui": "D049109", "major_topic": false }, { "descriptor": "Detergents", "descriptor_ui": "D003902", "major_topic": false }, { "descriptor": "Drug Design", "descriptor_ui": "D015195", "major_topic": false }, { "descriptor": "Enzyme Inhibitors", "descriptor_ui": "D004791", "major_topic": false }, { "descriptor": "HeLa Cells", "descriptor_ui": "D006367", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Phosphoric Monoester Hydrolases", "descriptor_ui": "D010744", "major_topic": false }, { "descriptor": "Structure-Activity Relationship", "descriptor_ui": "D013329", "major_topic": false }, { "descriptor": "Vaccinia virus", "descriptor_ui": "D014616", "major_topic": false }, { "descriptor": "Viral Proteins", "descriptor_ui": "D014764", "major_topic": false } ], "publication": { "conference_name": null, "date": "2014 May 1", "date_precision": "day", "issue": "9", "normalized_date": "2014-05-01", "pages": "2771-2782", "proceedings_title": null, "publisher": "", "title": "Bioorganic & medicinal chemistry", "volume": "22", "year": 2014 }, "ssbd": { "database": [], "repository": [] }, "title": "RE12 derivatives displaying Vaccinia H1-related phosphatase (VHR) inhibition in the presence of detergent and their anti-proliferative activity against HeLa cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The olfactory bulb (OB) is one of the two major loci in the mammalian brain where newborn neurons are constantly integrated into the neural circuit during postnatal life. Newborn neurons are generated from neural stem cells in the subventricular zone (SVZ) of the lateral ventricle and migrate to the OB through the rostral migratory stream. The majority of these newborn neurons differentiate into inhibitory interneurons, such as granule cells and periglomerular cells. It has been reported that prolonged supply of newborn neurons leads to continuous addition/turnover of the interneuronal populations and contributes to functional integrity of the OB circuit. However, it is not still clear how and to what extent postnatal-born neurons contribute to OB neural circuit formation, and the functional role of postnatal neurogenesis in odor-related behaviors remains elusive. To address this question, here by using genetic strategies, we first determined the unique integration mode of newly born interneurons during postnatal development of the mouse OB. We then manipulated these interneuron populations and found that continuous postnatal neurogenesis in the SVZ-OB plays pivotal roles in flexible olfactory associative learning and memory.", "classifications": [ { "id": "Imayoshi", "label": "Group Imayoshi", "parent": "Imayoshi", "type": "group" }, { "id": "Imayoshi", "label": "Team Imayoshi", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Masayuki", "last_name": "Sakamoto", "name": null }, { "creator_type": "author", "first_name": "Nao", "last_name": "Ieki", "name": null }, { "creator_type": "author", "first_name": "Goichi", "last_name": "Miyoshi", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Mochimaru", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Miyachi", "name": null }, { "creator_type": "author", "first_name": "Tetsuya", "last_name": "Imura", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Yamaguchi", "name": null }, { "creator_type": "author", "first_name": "Gord", "last_name": "Fishell", "name": null }, { "creator_type": "author", "first_name": "Kensaku", "last_name": "Mori", "name": null }, { "creator_type": "author", "first_name": "Ryoichiro", "last_name": "Kageyama", "name": null }, { "creator_type": "author", "first_name": "Itaru", "last_name": "Imayoshi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1523/jneurosci.0674-14.2014" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "24760839" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Association Learning", "descriptor_ui": "D001245", "major_topic": false }, { "descriptor": "Cerebral Ventricles", "descriptor_ui": "D002552", "major_topic": false }, { "descriptor": "Dentate Gyrus", "descriptor_ui": "D018891", "major_topic": false }, { "descriptor": "Interneurons", "descriptor_ui": "D007395", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Transgenic", "descriptor_ui": "D008822", "major_topic": false }, { "descriptor": "Nerve Net", "descriptor_ui": "D009415", "major_topic": false }, { "descriptor": "Neural Stem Cells", "descriptor_ui": "D058953", "major_topic": false }, { "descriptor": "Neurogenesis", "descriptor_ui": "D055495", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Odorants", "descriptor_ui": "D009812", "major_topic": false }, { "descriptor": "Olfactory Bulb", "descriptor_ui": "D009830", "major_topic": false }, { "descriptor": "Olfactory Perception", "descriptor_ui": "D055696", "major_topic": false } ], "publication": { "conference_name": null, "date": "2014 Apr 23", "date_precision": "day", "issue": "17", "normalized_date": "2014-04-23", "pages": "5788-5799", "proceedings_title": null, "publisher": "", "title": "The Journal of Neuroscience", "volume": "34", "year": 2014 }, "ssbd": { "database": [], "repository": [] }, "title": "Continuous Postnatal Neurogenesis Contributes to Formation of the Olfactory Bulb Neural Circuits and Flexible Olfactory Associative Learning.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Phosphorylation is considered a main mechanism modulating nNOS (neuronal nitric oxide synthase) function to reduce NO production. In the present study, the effects of nNOS phosphorylation on redox signalling, including that of NO, ROS (reactive oxygen species), and 8-nitro-cGMP (8-nitroguanosine 3',5'-cyclic monophosphate), a downstream messenger of redox signalling, were investigated. In vitro experiments revealed that a phosphorylation-mimic mutant of nNOS (Ser847 replaced with aspartic acid, 847D) increased uncoupling to produce a superoxide. In addition, nicotine, which triggers an influx of Ca2+, induced more ROS and 8-nitro-cGMP production in 847D-expressing PC12 cells than WT (wild-type)-expressing cells. Additionally, nicotine-induced phosphorylation of nNOS at Ser847 and increased ROS and 8-nitro-cGMP production in rat CGNs (cerebellar granule neurons). In CGNs, the NOS (nitric oxide synthase) inhibitor L-NAME (NG-nitro-L-arginine methyl ester) and superoxide dismutase completely inhibited ROS and 8-nitro-cGMP production, whereas the CaMK (Ca2+/calmodulin-dependent protein kinase) inhibitor KN93 mildly reduced this effect. Nicotine induced HO-1 (haem oxygenase 1) expression in CGNs and showed cytoprotective effects against apoptosis. Moreover, 8-nitro-cGMP treatment showed identical effects that were attenuated by KN93 pre-treatment. The present paper provides the first substantial corroboration for the biological effects of nNOS phosphorylation at Ser847 on redox signalling, including ROS and intracellular 8-nitro-cGMP generation in neurons, which possibly play roles in neuroprotection.", "classifications": [ { "id": "Akaike", "label": "Group Akaike", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Shingo", "last_name": "Kasamatsu", "name": null }, { "creator_type": "author", "first_name": "Yasuo", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Tomohiro", "last_name": "Sawa", "name": null }, { "creator_type": "author", "first_name": "Takaaki", "last_name": "Akaike", "name": null }, { "creator_type": "author", "first_name": "Hideshi", "last_name": "Ihara", "name": null } ], "identifiers": { "doi": { "normalized": "10.1042/bj20131262" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "24499461" } }, "mesh": [ { "descriptor": "Amino Acid Sequence", "descriptor_ui": "D000595", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Apoptosis", "descriptor_ui": "D017209", "major_topic": false }, { "descriptor": "Cerebellum", "descriptor_ui": "D002531", "major_topic": false }, { "descriptor": "Cyclic GMP", "descriptor_ui": "D006152", "major_topic": false }, { "descriptor": "Gene Expression Regulation, Enzymologic", "descriptor_ui": "D015971", "major_topic": false }, { "descriptor": "Heme Oxygenase-1", "descriptor_ui": "D051547", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Nicotine", "descriptor_ui": "D009538", "major_topic": false }, { "descriptor": "Nitric Oxide Synthase Type I", "descriptor_ui": "D052248", "major_topic": false }, { "descriptor": "Oxidation-Reduction", "descriptor_ui": "D010084", "major_topic": false }, { "descriptor": "PC12 Cells", "descriptor_ui": "D016716", "major_topic": false }, { "descriptor": "Phosphorylation", "descriptor_ui": "D010766", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": true } ], "publication": { "conference_name": null, "date": "2014 Apr 15", "date_precision": "day", "issue": "2", "normalized_date": "2014-04-15", "pages": "251-263", "proceedings_title": null, "publisher": "", "title": "The Biochemical journal", "volume": "459", "year": 2014 }, "ssbd": { "database": [], "repository": [] }, "title": "Redox signal regulation via nNOS phosphorylation at Ser847 in PC12 cells and rat cerebellar granule neurons.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The synchronized patterns of hair follicle growth and expansion of the dermal adipocyte layer have long been recognized. Although factors secreted by adipocytes are known to regulate the hair growth cycle, it is unclear whether, conversely, the epidermis can regulate adipogenesis. Our study now demonstrates that activation of epidermal Wnt/β-catenin signaling stimulates adipocyte differentiation in vivo and in vitro. The effect can be mediated by secreted factors, including insulin-like growth factor 2 and bone morphogenetic proteins 2 and 6.", "classifications": [ { "id": "Fujiwara", "label": "Group Fujiwara", "parent": "Fujiwara", "type": "group" }, { "id": "Fujiwara", "label": "Team Fujiwara", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Giacomo", "last_name": "Donati", "name": null }, { "creator_type": "author", "first_name": "Valentina", "last_name": "Proserpio", "name": null }, { "creator_type": "author", "first_name": "Beate Maria", "last_name": "Lichtenberger", "name": null }, { "creator_type": "author", "first_name": "Ken", "last_name": "Natsuga", "name": null }, { "creator_type": "author", "first_name": "Rodney", "last_name": "Sinclair", "name": null }, { "creator_type": "author", "first_name": "Hironobu", "last_name": "Fujiwara", "name": null }, { "creator_type": "author", "first_name": "Fiona M.", "last_name": "Watt", "name": null } ], "identifiers": { "doi": { "normalized": "10.1073/pnas.1312880111" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "24706781" } }, "mesh": [ { "descriptor": "3T3-L1 Cells", "descriptor_ui": "D041721", "major_topic": false }, { "descriptor": "Adipocytes", "descriptor_ui": "D017667", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Azo Compounds", "descriptor_ui": "D001391", "major_topic": false }, { "descriptor": "beta Catenin", "descriptor_ui": "D051176", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Cluster Analysis", "descriptor_ui": "D016000", "major_topic": false }, { "descriptor": "Epidermal Cells", "descriptor_ui": "D000078404", "major_topic": false }, { "descriptor": "Epidermis", "descriptor_ui": "D004817", "major_topic": false }, { "descriptor": "Flow Cytometry", "descriptor_ui": "D005434", "major_topic": false }, { "descriptor": "Hair Follicle", "descriptor_ui": "D018859", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Keratinocytes", "descriptor_ui": "D015603", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Wnt Signaling Pathway", "descriptor_ui": "D060449", "major_topic": false } ], "publication": { "conference_name": null, "date": "2014 Apr 15", "date_precision": "day", "issue": "15", "normalized_date": "2014-04-15", "pages": "E1501-1509", "proceedings_title": null, "publisher": "", "title": "Proceedings of the National Academy of Sciences of the United States of America", "volume": "111", "year": 2014 }, "ssbd": { "database": [], "repository": [] }, "title": "Epidermal Wnt/β-catenin signaling regulates adipocyte differentiation via secretion of adipogenic factors.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Helicobacter cinaedi is the most common enterohepatic Helicobacter species that causes bacteremia in humans, but its pathogenicity is unclear. Here, we investigated the possible association of H. cinaedi with atherosclerosis in vivo and in vitro. We found that H. cinaedi infection significantly enhanced atherosclerosis in hyperlipidaemic mice. Aortic root lesions in infected mice showed increased accumulation of neutrophils and F4/80(+) foam cells, which was due, at least partly, to bacteria-mediated increased expression of proinflammatory genes. Although infection was asymptomatic, detection of cytolethal distending toxin RNA of H. cinaedi indicated aorta infection. H. cinaedi infection altered expression of cholesterol receptors and transporters in cultured macrophages and caused foam cell formation. Also, infection induced differentiation of THP-1 monocytes. These data provide the first evidence of a pathogenic role of H. cinaedi in atherosclerosis in experimental models, thereby justifying additional investigations of the possible role of enterohepatic Helicobacter spp. in atherosclerosis and cardiovascular disease.", "classifications": [ { "id": "Akaike", "label": "Group Akaike", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Shahzada", "last_name": "Khan", "name": null }, { "creator_type": "author", "first_name": "H. N. Ashiqur", "last_name": "Rahman", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Okamoto", "name": null }, { "creator_type": "author", "first_name": "Tetsuro", "last_name": "Matsunaga", "name": null }, { "creator_type": "author", "first_name": "Yukio", "last_name": "Fujiwara", "name": null }, { "creator_type": "author", "first_name": "Tomohiro", "last_name": "Sawa", "name": null }, { "creator_type": "author", "first_name": "Jun", "last_name": "Yoshitake", "name": null }, { "creator_type": "author", "first_name": "Katsuhiko", "last_name": "Ono", "name": null }, { "creator_type": "author", "first_name": "Khandaker Ahtesham", "last_name": "Ahmed", "name": null }, { "creator_type": "author", "first_name": "Md Mizanur", "last_name": "Rahaman", "name": null }, { "creator_type": "author", "first_name": "Kohta", "last_name": "Oyama", "name": null }, { "creator_type": "author", "first_name": "Motohiro", "last_name": "Takeya", "name": null }, { "creator_type": "author", "first_name": "Tomoaki", "last_name": "Ida", "name": null }, { "creator_type": "author", "first_name": "Yoshiaki", "last_name": "Kawamura", "name": null }, { "creator_type": "author", "first_name": "Shigemoto", "last_name": "Fujii", "name": null }, { "creator_type": "author", "first_name": "Takaaki", "last_name": "Akaike", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/srep04680" }, "pmcid": { "normalized": "PMC3986732" }, "pmid": { "normalized": "24732347" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Aorta", "descriptor_ui": "D001011", "major_topic": false }, { "descriptor": "Atherosclerosis", "descriptor_ui": "D050197", "major_topic": false }, { "descriptor": "Cardiovascular Diseases", "descriptor_ui": "D002318", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "DNA, Bacterial", "descriptor_ui": "D004269", "major_topic": false }, { "descriptor": "Foam Cells", "descriptor_ui": "D005487", "major_topic": false }, { "descriptor": "Helicobacter Infections", "descriptor_ui": "D016481", "major_topic": false }, { "descriptor": "Helicobacter pylori", "descriptor_ui": "D016480", "major_topic": false }, { "descriptor": "Hyperlipidemias", "descriptor_ui": "D006949", "major_topic": false }, { "descriptor": "Inflammation", "descriptor_ui": "D007249", "major_topic": false }, { "descriptor": "Macrophages", "descriptor_ui": "D008264", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Monocytes", "descriptor_ui": "D009000", "major_topic": false }, { "descriptor": "Neutrophils", "descriptor_ui": "D009504", "major_topic": false }, { "descriptor": "Nitric Oxide Synthase Type III", "descriptor_ui": "D052250", "major_topic": false }, { "descriptor": "Receptors, LDL", "descriptor_ui": "D011973", "major_topic": false }, { "descriptor": "RNA, Bacterial", "descriptor_ui": "D012329", "major_topic": false } ], "publication": { "conference_name": null, "date": "2014 Apr 15", "date_precision": "day", "issue": "", "normalized_date": "2014-04-15", "pages": "4680", "proceedings_title": null, "publisher": "", "title": "Scientific reports", "volume": "4", "year": 2014 }, "ssbd": { "database": [], "repository": [] }, "title": "Promotion of atherosclerosis by Helicobacter cinaedi infection that involves macrophage-driven proinflammatory responses.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Multipotent neural progenitor cells (NPCs) undergo self-renewal while producing neurons, astrocytes, and oligodendrocytes. These processes are controlled by multiple basic helix-loop-helix (bHLH) fate determination factors, which exhibit different functions by posttranslational modifications. Furthermore, depending on the expression dynamics, each bHLH factor seems to have two contradictory functions, promoting NPC proliferation and cell-cycle exit for differentiation. The oscillatory expression of multiple bHLH factors correlates with the multipotent and proliferative state, whereas sustained expression of a selected single bHLH factor regulates the fate determination. bHLH factors also regulate direct reprogramming of adult somatic cells into neurons and oligodendrocytes. Thus, bHLH factors play key roles in development and regeneration of the nervous system. Here, we review versatile functions of bHLH factors, focusing on telencephalic development.", "classifications": [ { "id": "Imayoshi", "label": "Group Imayoshi", "parent": "Imayoshi", "type": "group" }, { "id": "Imayoshi", "label": "Team Imayoshi", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Itaru", "last_name": "Imayoshi", "name": null }, { "creator_type": "author", "first_name": "Ryoichiro", "last_name": "Kageyama", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.neuron.2014.03.018" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "24698265" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Basic Helix-Loop-Helix Proteins", "descriptor_ui": "D051792", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": true }, { "descriptor": "Neural Stem Cells", "descriptor_ui": "D058953", "major_topic": false }, { "descriptor": "Neuroglia", "descriptor_ui": "D009457", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Regeneration", "descriptor_ui": "D012038", "major_topic": false } ], "publication": { "conference_name": null, "date": "2014 Apr 2", "date_precision": "day", "issue": "1", "normalized_date": "2014-04-02", "pages": "9-23", "proceedings_title": null, "publisher": "", "title": "Neuron", "volume": "82", "year": 2014 }, "ssbd": { "database": [], "repository": [] }, "title": "bHLH factors in self-renewal, multipotency, and fate choice of neural progenitor cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Ca(2+)/Calmodulin-dependent protein kinase II (CaMKII) has been shown to play a major role in establishing memories through complex molecular interactions including phosphorylation of multiple synaptic targets. However, it is still controversial whether CaMKII itself serves as a molecular memory because of a lack of direct evidence. Here, we show that a single holoenzyme of CaMKII per se serves as an erasable molecular memory switch. We reconstituted Ca(2+)/Calmodulin-dependent CaMKII autophosphorylation in the presence of protein phosphatase 1 in vitro, and found that CaMKII phosphorylation shows a switch-like response with history dependence (hysteresis) only in the presence of an N-methyl-D-aspartate receptor-derived peptide. This hysteresis is Ca(2+) and protein phosphatase 1 concentration-dependent, indicating that the CaMKII memory switch is not simply caused by an N-methyl-D-aspartate receptor-derived peptide lock of CaMKII in an active conformation. Mutation of a phosphorylation site of the peptide shifted the Ca(2+) range of hysteresis. These functions may be crucial for induction and maintenance of long-term synaptic plasticity at hippocampal synapses.", "classifications": [ { "id": "Kuroda", "label": "Group Kuroda", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Hidetoshi", "last_name": "Urakubo", "name": null }, { "creator_type": "author", "first_name": "Miharu", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Shin", "last_name": "Ishii", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Kuroda", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.bpj.2014.01.026" }, "pmcid": { "normalized": "PMC3985500" }, "pmid": { "normalized": "24655517" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Calcium", "descriptor_ui": "D002118", "major_topic": false }, { "descriptor": "Calcium-Calmodulin-Dependent Protein Kinase Type 2", "descriptor_ui": "D054732", "major_topic": false }, { "descriptor": "Kinetics", "descriptor_ui": "D007700", "major_topic": false }, { "descriptor": "Peptide Fragments", "descriptor_ui": "D010446", "major_topic": false }, { "descriptor": "Phosphorylation", "descriptor_ui": "D010766", "major_topic": false }, { "descriptor": "Protein Binding", "descriptor_ui": "D011485", "major_topic": false }, { "descriptor": "Protein Phosphatase 1", "descriptor_ui": "D054645", "major_topic": false }, { "descriptor": "Protein Structure, Tertiary", "descriptor_ui": "D017434", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Receptors, N-Methyl-D-Aspartate", "descriptor_ui": "D016194", "major_topic": false }, { "descriptor": "Sf9 Cells", "descriptor_ui": "D061987", "major_topic": false }, { "descriptor": "Spodoptera", "descriptor_ui": "D018411", "major_topic": false } ], "publication": { "conference_name": null, "date": "2014 Mar 18", "date_precision": "day", "issue": "6", "normalized_date": "2014-03-18", "pages": "1414-1420", "proceedings_title": null, "publisher": "", "title": "Biophysical journal", "volume": "106", "year": 2014 }, "ssbd": { "database": [], "repository": [] }, "title": "In vitro reconstitution of a CaMKII memory switch by an NMDA receptor-derived peptide.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Saturated excitation (SAX) microscopy utilizes the nonlinear relation between fluorescence emission and excitation under saturated excitation to improve the spatial resolution of confocal microscopy. In this study, we theoretically and experimentally investigate the saturation of fluorescence excitation under modulated excitation to optimize the excitation conditions for SAX microscopy. Calculation of the relationships between fluorescence and excitation intensity with different modulation frequencies reveals that the lifetime of the triplet state of the fluorescent probe strongly affects the strength of the demodulated fluorescence signals. We also find that photobleaching shows little dependence on the modulation frequency. These investigations allow us to determine the optimum excitation conditions, that is, the conditions providing sufficient fluorescence saturation without strong photobleaching. For a sample stained with ATTO Rho6G phalloidin, we estimate the optimal excitation conditions, which are produced with 50 kHz excitation modulation and a 50 musec pixel dwell time, and successfully perform three-dimensional imaging with sub-diffraction resolution.", "classifications": [ { "id": "Fujita", "label": "Group Fujita", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yasuo", "last_name": "Yonemaru", "name": null }, { "creator_type": "author", "first_name": "Masahito", "last_name": "Yamanaka", "name": null }, { "creator_type": "author", "first_name": "Nicholas I.", "last_name": "Smith", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Kawata", "name": null }, { "creator_type": "author", "first_name": "Katsumasa", "last_name": "Fujita", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/cphc.201300879" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "24488765" } }, "mesh": [ { "descriptor": "Fluorescence", "descriptor_ui": "D005453", "major_topic": false }, { "descriptor": "Fluorescent Dyes", "descriptor_ui": "D005456", "major_topic": false }, { "descriptor": "HeLa Cells", "descriptor_ui": "D006367", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Microscopy, Fluorescence", "descriptor_ui": "D008856", "major_topic": false }, { "descriptor": "Phalloidine", "descriptor_ui": "D010590", "major_topic": false } ], "publication": { "conference_name": null, "date": "2014 Mar 17", "date_precision": "day", "issue": "4", "normalized_date": "2014-03-17", "pages": "743-749", "proceedings_title": null, "publisher": "", "title": "Chemphyschem : a European journal of chemical physics and physical chemistry", "volume": "15", "year": 2014 }, "ssbd": { "database": [], "repository": [] }, "title": "Saturated excitation microscopy with optimized excitation modulation.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Mdm2, a ubiquitin ligase and downstream effector of p53, attenuates the proliferative potential of primary cells via ubiquitination and degradation of the glycolytic enzyme PGAM under senescence-inducing stress.", "classifications": [ { "id": "Okamoto", "label": "Group Okamoto", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Takumi", "last_name": "Mikawa", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Maruyama", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Okamoto", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Nakagama", "name": null }, { "creator_type": "author", "first_name": "Matilde E.", "last_name": "Lleonart", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Tsusaka", "name": null }, { "creator_type": "author", "first_name": "Kousuke", "last_name": "Hori", "name": null }, { "creator_type": "author", "first_name": "Itsuo", "last_name": "Murakami", "name": null }, { "creator_type": "author", "first_name": "Taisuke", "last_name": "Izumi", "name": null }, { "creator_type": "author", "first_name": "Akifumi", "last_name": "Takaori-Kondo", "name": null }, { "creator_type": "author", "first_name": "Masayuki", "last_name": "Yokode", "name": null }, { "creator_type": "author", "first_name": "Gordon", "last_name": "Peters", "name": null }, { "creator_type": "author", "first_name": "David", "last_name": "Beach", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Kondoh", "name": null } ], "identifiers": { "doi": { "normalized": "10.1083/jcb.201306149" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "24567357" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "Cellular Senescence", "descriptor_ui": "D016922", "major_topic": true }, { "descriptor": "DNA Damage", "descriptor_ui": "D004249", "major_topic": false }, { "descriptor": "Down-Regulation", "descriptor_ui": "D015536", "major_topic": false }, { "descriptor": "HCT116 Cells", "descriptor_ui": "D045325", "major_topic": false }, { "descriptor": "HEK293 Cells", "descriptor_ui": "D057809", "major_topic": false }, { "descriptor": "HeLa Cells", "descriptor_ui": "D006367", "major_topic": false }, { "descriptor": "HT29 Cells", "descriptor_ui": "D019073", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Nude", "descriptor_ui": "D008819", "major_topic": false }, { "descriptor": "p21-Activated Kinases", "descriptor_ui": "D054462", "major_topic": false }, { "descriptor": "Phosphoglycerate Mutase", "descriptor_ui": "D010736", "major_topic": false }, { "descriptor": "Phosphorylation", "descriptor_ui": "D010766", "major_topic": false }, { "descriptor": "Proteolysis", "descriptor_ui": "D059748", "major_topic": false }, { "descriptor": "Proto-Oncogene Proteins c-mdm2", "descriptor_ui": "D051736", "major_topic": false }, { "descriptor": "Stress, Physiological", "descriptor_ui": "D013312", "major_topic": true }, { "descriptor": "Ubiquitin", "descriptor_ui": "D025801", "major_topic": false } ], "publication": { "conference_name": null, "date": "2014 Mar 3", "date_precision": "day", "issue": "5", "normalized_date": "2014-03-03", "pages": "729-745", "proceedings_title": null, "publisher": "", "title": "The Journal of Cell Biology", "volume": "204", "year": 2014 }, "ssbd": { "database": [], "repository": [] }, "title": "Senescence-inducing stress promotes proteolysis of phosphoglycerate mutase via ubiquitin ligase Mdm2.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Cancer is believed to arise primarily through accumulation of genetic mutations. Although induced pluripotent stem cell (iPSC) generation does not require changes in genomic sequence, iPSCs acquire unlimited growth potential, a characteristic shared with cancer cells. Here, we describe a murine system in which reprogramming factor expression in vivo can be controlled temporally with doxycycline (Dox). Notably, transient expression of reprogramming factors in vivo results in tumor development in various tissues consisting of undifferentiated dysplastic cells exhibiting global changes in DNA methylation patterns. The Dox-withdrawn tumors arising in the kidney share a number of characteristics with Wilms tumor, a common pediatric kidney cancer. We also demonstrate that iPSCs derived from Dox-withdrawn kidney tumor cells give rise to nonneoplastic kidney cells in mice, proving that they have not undergone irreversible genetic transformation. These findings suggest that epigenetic regulation associated with iPSC derivation may drive development of particular types of cancer.", "classifications": [ { "id": "Yamamoto", "label": "Group Yamamoto", "parent": "Toyoshima", "type": "group" }, { "id": "Toyoshima", "label": "Team Toyoshima", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Kotaro", "last_name": "Ohnishi", "name": null }, { "creator_type": "author", "first_name": "Katsunori", "last_name": "Semi", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Masahito", "last_name": "Shimizu", "name": null }, { "creator_type": "author", "first_name": "Akito", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Kanae", "last_name": "Mitsunaga", "name": null }, { "creator_type": "author", "first_name": "Keisuke", "last_name": "Okita", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Osafune", "name": null }, { "creator_type": "author", "first_name": "Yuko", "last_name": "Arioka", "name": null }, { "creator_type": "author", "first_name": "Toshiyuki", "last_name": "Maeda", "name": null }, { "creator_type": "author", "first_name": "Hidenobu", "last_name": "Soejima", "name": null }, { "creator_type": "author", "first_name": "Hisataka", "last_name": "Moriwaki", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Yamanaka", "name": null }, { "creator_type": "author", "first_name": "Knut", "last_name": "Woltjen", "name": null }, { "creator_type": "author", "first_name": "Yasuhiro", "last_name": "Yamada", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.cell.2014.01.005" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "24529372" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cellular Reprogramming", "descriptor_ui": "D065150", "major_topic": true }, { "descriptor": "DNA Methylation", "descriptor_ui": "D019175", "major_topic": false }, { "descriptor": "Doxycycline", "descriptor_ui": "D004318", "major_topic": false }, { "descriptor": "Epigenesis, Genetic", "descriptor_ui": "D044127", "major_topic": true }, { "descriptor": "Gene Expression Regulation, Neoplastic", "descriptor_ui": "D015972", "major_topic": true }, { "descriptor": "Induced Pluripotent Stem Cells", "descriptor_ui": "D057026", "major_topic": false }, { "descriptor": "Kidney Neoplasms", "descriptor_ui": "D007680", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Transgenic", "descriptor_ui": "D008822", "major_topic": false }, { "descriptor": "Transcription Factors", "descriptor_ui": "D014157", "major_topic": false } ], "publication": { "conference_name": null, "date": "2014 Feb 13", "date_precision": "day", "issue": "4", "normalized_date": "2014-02-13", "pages": "663-677", "proceedings_title": null, "publisher": "", "title": "Cell", "volume": "156", "year": 2014 }, "ssbd": { "database": [], "repository": [] }, "title": "Premature termination of reprogramming in vivo leads to cancer development through altered epigenetic regulation.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "We report the simultaneous imaging of protonated and deprotonated forms of carbonylcyanide p-trifluoromethoxy-phenylhydrazone (FCCP) molecules in live cells by Raman microscopy. Nitriles, structure-sensitive Raman tags, are used to detect the two distinct molecular structures, demonstrating the potential of Raman microscopy for structure-based imaging of bioactive small molecules.", "classifications": [ { "id": "Sodeoka", "label": "Group Sodeoka", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Yamakoshi", "name": null }, { "creator_type": "author", "first_name": "Almar F.", "last_name": "Palonpon", "name": null }, { "creator_type": "author", "first_name": "Kosuke", "last_name": "Dodo", "name": null }, { "creator_type": "author", "first_name": "Jun", "last_name": "Ando", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Kawata", "name": null }, { "creator_type": "author", "first_name": "Katsumasa", "last_name": "Fujita", "name": null }, { "creator_type": "author", "first_name": "Mikiko", "last_name": "Sodeoka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1039/c3cc48587k" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "24346645" } }, "mesh": [ { "descriptor": "Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone", "descriptor_ui": "D002259", "major_topic": false }, { "descriptor": "Cell Nucleus", "descriptor_ui": "D002467", "major_topic": false }, { "descriptor": "Cytoplasm", "descriptor_ui": "D003593", "major_topic": false }, { "descriptor": "HeLa Cells", "descriptor_ui": "D006367", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Lipids", "descriptor_ui": "D008055", "major_topic": false }, { "descriptor": "Microscopy", "descriptor_ui": "D008853", "major_topic": false }, { "descriptor": "Protons", "descriptor_ui": "D011522", "major_topic": true }, { "descriptor": "Spectrum Analysis, Raman", "descriptor_ui": "D013059", "major_topic": false } ], "publication": { "conference_name": null, "date": "2014 Feb 9", "date_precision": "day", "issue": "11", "normalized_date": "2014-02-09", "pages": "1341-1343", "proceedings_title": null, "publisher": "", "title": "Chemical communications (Cambridge, England)", "volume": "50", "year": 2014 }, "ssbd": { "database": [], "repository": [] }, "title": "Simultaneous imaging of protonated and deprotonated carbonylcyanide p-trifluoromethoxyphenylhydrazone in live cells by Raman microscopy.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The quiescent (G0) phase of the cell cycle is the reversible phase from which the cells exit from the cell cycle. Due to the difficulty of defining the G0 phase, quiescent cells have not been well characterized. In this study, a fusion protein consisting of mVenus and a defective mutant of CDK inhibitor, p27 (p27K(-)) was shown to be able to identify and isolate a population of quiescent cells and to effectively visualize the G0 to G1 transition. By comparing the expression profiles of the G0 and G1 cells defined by mVenus-p27K(-), we have identified molecular features of quiescent cells. Quiescence is also an important feature of many types of stem cells, and mVenus-p27K(-)-transgenic mice enabled the detection of the quiescent cells with muscle stem cell markers in muscle in vivo. The mVenus-p27K(-) probe could be useful in investigating stem cells as well as quiescent cells.", "classifications": [ { "id": "Sawano", "label": "Group Sawano", "parent": "Shintaku", "type": "group" }, { "id": "Shintaku", "label": "Team Shintaku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Toshihiko", "last_name": "Oki", "name": null }, { "creator_type": "author", "first_name": "Koutarou", "last_name": "Nishimura", "name": null }, { "creator_type": "author", "first_name": "Jiro", "last_name": "Kitaura", "name": null }, { "creator_type": "author", "first_name": "Katsuhiro", "last_name": "Togami", "name": null }, { "creator_type": "author", "first_name": "Akie", "last_name": "Maehara", "name": null }, { "creator_type": "author", "first_name": "Kumi", "last_name": "Izawa", "name": null }, { "creator_type": "author", "first_name": "Asako", "last_name": "Sakaue-Sawano", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Niida", "name": null }, { "creator_type": "author", "first_name": "Satoru", "last_name": "Miyano", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Aburatani", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Kiyonari", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Miyawaki", "name": null }, { "creator_type": "author", "first_name": "Toshio", "last_name": "Kitamura", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/srep04012" }, "pmcid": { "normalized": "PMC3915272" }, "pmid": { "normalized": "24500246" } }, "mesh": [ { "descriptor": "3T3 Cells", "descriptor_ui": "D016475", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Apoptosis Regulatory Proteins", "descriptor_ui": "D051017", "major_topic": false }, { "descriptor": "Bacterial Proteins", "descriptor_ui": "D001426", "major_topic": false }, { "descriptor": "Carrier Proteins", "descriptor_ui": "D002352", "major_topic": false }, { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "Cyclin-Dependent Kinase Inhibitor p16", "descriptor_ui": "D019941", "major_topic": false }, { "descriptor": "Cyclin-Dependent Kinase Inhibitor p21", "descriptor_ui": "D050759", "major_topic": false }, { "descriptor": "Cyclin-Dependent Kinase Inhibitor p27", "descriptor_ui": "D050760", "major_topic": false }, { "descriptor": "Cyclin-Dependent Kinase Inhibitor p57", "descriptor_ui": "D050761", "major_topic": false }, { "descriptor": "G1 Phase", "descriptor_ui": "D016193", "major_topic": false }, { "descriptor": "Gene Expression", "descriptor_ui": "D015870", "major_topic": false }, { "descriptor": "Intracellular Signaling Peptides and Proteins", "descriptor_ui": "D047908", "major_topic": false }, { "descriptor": "Luminescent Proteins", "descriptor_ui": "D008164", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Transgenic", "descriptor_ui": "D008822", "major_topic": false }, { "descriptor": "MicroRNAs", "descriptor_ui": "D035683", "major_topic": false }, { "descriptor": "Recombinant Fusion Proteins", "descriptor_ui": "D011993", "major_topic": false }, { "descriptor": "Resting Phase, Cell Cycle", "descriptor_ui": "D016192", "major_topic": false }, { "descriptor": "Retinoblastoma Protein", "descriptor_ui": "D016160", "major_topic": false }, { "descriptor": "RNA-Binding Proteins", "descriptor_ui": "D016601", "major_topic": false }, { "descriptor": "Selenium-Binding Proteins", "descriptor_ui": "D051137", "major_topic": false }, { "descriptor": "Stem Cells", "descriptor_ui": "D013234", "major_topic": false }, { "descriptor": "Tumor Suppressor Protein p53", "descriptor_ui": "D016159", "major_topic": false } ], "publication": { "conference_name": null, "date": "2014 Feb 6", "date_precision": "day", "issue": "", "normalized_date": "2014-02-06", "pages": "4012", "proceedings_title": null, "publisher": "", "title": "Scientific reports", "volume": "4", "year": 2014 }, "ssbd": { "database": [], "repository": [] }, "title": "A novel cell-cycle-indicator, mVenus-p27K-, identifies quiescent cells and visualizes G0-G1 transition.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: Neovascularization is necessary for follicular growth. Vascularization is first observed in preantral follicles, and thereafter the vasculature markedly increases in follicles undergoing development. Neovascularization includes angiogenesis and vasculogenesis. Vasculogenesis is the formation of new blood vessels by bone marrow-derived endothelial progenitor cells. It is unclear whether vasculogenesis occurs during follicular growth. Blood vessels must be mature to be functional blood vessels. Mature blood vessels are characterized by the recruitment of pericytes. However, it is unclear where pericytes come from and whether they contribute to neovascularization in the follicle during follicular growth. In this study, we investigated whether bone marrow-derived progenitor cells that differentiate into vascular endothelial cells or pericytes contribute to neovascularization during follicular growth. METHODS: A parabiosis model was used in this study. Six-week-old wild-type and transgenic female mice expressing green fluorescent protein (GFP) were conjoined between the lateral abdominal regions to create a shared circulatory system. After 6 weeks, the ovaries were obtained and immunostained for CD31/CD34 (a vascular endothelial cell marker), platelet-derived growth factor receptor-β (PDGFR-β) (a pericyte marker), and GFP (a bone marrow-derived cell marker). RESULTS: Cells that were positive for CD34 and PDGFR-β were observed in the stroma adjacent to the primary or early preantral follicles and in the theca cell layer of the follicles from the late preantral stage to the preovulatory stage. CD31/CD34 and GFP double-positive cells were observed in the theca cell layer of the follicle from the antral stage to the preovulatory stage while the number of double-positive cells in the preovulatory follicles did not increase. PDGFR-β and GFP double-positive cells were observed in the theca cell layer of the preovulatory follicle but not in the smaller follicle. CONCLUSIONS: Locally existing endothelial cells and pericytes in the stroma play a central role in the neovascularization during follicular growth, while bone marrow-derived endothelial cells and pericytes partially contribute to this process.", "classifications": [ { "id": "Suzuki", "label": "Group Suzuki", "parent": "Takekawa", "type": "group" }, { "id": "Takekawa", "label": "Team Takekawa", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Fumie", "last_name": "Kizuka-Shibuya", "name": null }, { "creator_type": "author", "first_name": "Nobuko", "last_name": "Tokuda", "name": null }, { "creator_type": "author", "first_name": "Kiyoshi", "last_name": "Takagi", "name": null }, { "creator_type": "author", "first_name": "Yasuhiro", "last_name": "Adachi", "name": null }, { "creator_type": "author", "first_name": "Lifa", "last_name": "Lee", "name": null }, { "creator_type": "author", "first_name": "Isao", "last_name": "Tamura", "name": null }, { "creator_type": "author", "first_name": "Ryo", "last_name": "Maekawa", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Tamura", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Yuji", "last_name": "Owada", "name": null }, { "creator_type": "author", "first_name": "Norihiro", "last_name": "Sugino", "name": null } ], "identifiers": { "doi": { "normalized": "10.1186/1757-2215-7-10" }, "pmcid": { "normalized": "PMC3905919" }, "pmid": { "normalized": "24444000" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Antigens, CD34", "descriptor_ui": "D018952", "major_topic": false }, { "descriptor": "Biomarkers", "descriptor_ui": "D015415", "major_topic": false }, { "descriptor": "Cell Communication", "descriptor_ui": "D002450", "major_topic": true }, { "descriptor": "Endothelial Cells", "descriptor_ui": "D042783", "major_topic": false }, { "descriptor": "Endothelial Progenitor Cells", "descriptor_ui": "D066026", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Green Fluorescent Proteins", "descriptor_ui": "D049452", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Transgenic", "descriptor_ui": "D008822", "major_topic": false }, { "descriptor": "Neovascularization, Physiologic", "descriptor_ui": "D018919", "major_topic": true }, { "descriptor": "Ovarian Follicle", "descriptor_ui": "D006080", "major_topic": false }, { "descriptor": "Parabiosis", "descriptor_ui": "D010227", "major_topic": false }, { "descriptor": "Pericytes", "descriptor_ui": "D020286", "major_topic": false }, { "descriptor": "Platelet Endothelial Cell Adhesion Molecule-1", "descriptor_ui": "D019408", "major_topic": false }, { "descriptor": "Receptor, Platelet-Derived Growth Factor beta", "descriptor_ui": "D020797", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Stromal Cells", "descriptor_ui": "D017154", "major_topic": false } ], "publication": { "conference_name": null, "date": "2014 Jan 21", "date_precision": "day", "issue": "", "normalized_date": "2014-01-21", "pages": "10", "proceedings_title": null, "publisher": "", "title": "Journal of ovarian research", "volume": "7", "year": 2014 }, "ssbd": { "database": [], "repository": [] }, "title": "Locally existing endothelial cells and pericytes in ovarian stroma, but not bone marrow-derived vascular progenitor cells, play a central role in neovascularization during follicular development in mice.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Triarylmethanes, which are valuable structures in materials, sensing and pharmaceuticals, have been synthesized starting from methyl phenyl sulfone as an inexpensive and readily available template. The three aryl groups were installed through two sequential palladium-catalyzed C-H arylation reactions, followed by an arylative desulfonation. This method provides a new synthetic approach to multisubstituted triarylmethanes using readily available haloarenes and aryl boronic acids, and is also valuable for the preparation of unexplored triarylmethane-based materials and pharmaceuticals.", "classifications": [ { "id": "Nanbo", "label": "Group Nanbo", "parent": "Tsuchiya", "type": "group" }, { "id": "Tsuchiya", "label": "Team Tsuchiya", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Masakazu", "last_name": "Nambo", "name": null }, { "creator_type": "author", "first_name": "Cathleen M.", "last_name": "Crudden", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/anie.201307019" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "24307286" } }, "mesh": [ { "descriptor": "Antineoplastic Agents", "descriptor_ui": "D000970", "major_topic": false }, { "descriptor": "Boronic Acids", "descriptor_ui": "D001897", "major_topic": false }, { "descriptor": "Carbon", "descriptor_ui": "D002244", "major_topic": false }, { "descriptor": "Catalysis", "descriptor_ui": "D002384", "major_topic": false }, { "descriptor": "Dimethyl Sulfoxide", "descriptor_ui": "D004121", "major_topic": false }, { "descriptor": "Hydrogen", "descriptor_ui": "D006859", "major_topic": false }, { "descriptor": "Methane", "descriptor_ui": "D008697", "major_topic": false }, { "descriptor": "Palladium", "descriptor_ui": "D010165", "major_topic": false }, { "descriptor": "Sulfones", "descriptor_ui": "D013450", "major_topic": false } ], "publication": { "conference_name": null, "date": "2014 Jan 13", "date_precision": "day", "issue": "3", "normalized_date": "2014-01-13", "pages": "742-746", "proceedings_title": null, "publisher": "", "title": "Angewandte Chemie (International ed. in English)", "volume": "53", "year": 2014 }, "ssbd": { "database": [], "repository": [] }, "title": "Modular synthesis of triarylmethanes through palladium-catalyzed sequential arylation of methyl phenyl sulfone.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "We show that scattering from a single gold nanoparticle is saturable for the first time. Wavelength-dependent study reveals that the saturation behavior is governed by depletion of surface plasmon resonance, not the thermal effect. We observed interesting flattening of the point spread function of scattering from a single nanoparticle due to saturation. By extracting the saturated part of scattering via temporal modulation, we achieve lambda/8 point spread function in far-field imaging with unambiguous separation of adjacent particles.", "classifications": [ { "id": "Fujita", "label": "Group Fujita", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Shi-Wei", "last_name": "Chu", "name": null }, { "creator_type": "author", "first_name": "Tung-Yu", "last_name": "Su", "name": null }, { "creator_type": "author", "first_name": "Ryosuke", "last_name": "Oketani", "name": null }, { "creator_type": "author", "first_name": "Yen-Ta", "last_name": "Huang", "name": null }, { "creator_type": "author", "first_name": "Hsueh-Yu", "last_name": "Wu", "name": null }, { "creator_type": "author", "first_name": "Yasuo", "last_name": "Yonemaru", "name": null }, { "creator_type": "author", "first_name": "Masahito", "last_name": "Yamanaka", "name": null }, { "creator_type": "author", "first_name": "Hsuan", "last_name": "Lee", "name": null }, { "creator_type": "author", "first_name": "Guan-Yu", "last_name": "Zhuo", "name": null }, { "creator_type": "author", "first_name": "Ming-Ying", "last_name": "Lee", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Kawata", "name": null }, { "creator_type": "author", "first_name": "Katsumasa", "last_name": "Fujita", "name": null } ], "identifiers": { "doi": { "normalized": "10.1103/physrevlett.112.017402" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "24483931" } }, "mesh": [ { "descriptor": "Gold", "descriptor_ui": "D006046", "major_topic": false }, { "descriptor": "Metal Nanoparticles", "descriptor_ui": "D053768", "major_topic": false }, { "descriptor": "Microscopy", "descriptor_ui": "D008853", "major_topic": false }, { "descriptor": "Nanotechnology", "descriptor_ui": "D036103", "major_topic": false }, { "descriptor": "Surface Plasmon Resonance", "descriptor_ui": "D020349", "major_topic": false } ], "publication": { "conference_name": null, "date": "2014 Jan 10", "date_precision": "day", "issue": "1", "normalized_date": "2014-01-10", "pages": "017402", "proceedings_title": null, "publisher": "", "title": "Physical review letters", "volume": "112", "year": 2014 }, "ssbd": { "database": [], "repository": [] }, "title": "Measurement of a saturated emission of optical radiation from gold nanoparticles: application to an ultrahigh resolution microscope.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Cellular sensory systems often respond not to the absolute levels of inputs but to the fold-changes in inputs. Such a property is called fold-change detection (FCD) and is important for accurately sensing dynamic changes in environmental signals in the presence of fluctuations in their absolute levels. Previous studies defined FCD as input-scale invariance and proposed several biochemical models that achieve such a condition. Here, we prove that the previous FCD models can be approximated by a log-differentiator. Although the log-differentiator satisfies the input-scale invariance requirement, its response amplitude and response duration strongly depend on the input timescale. This creates limitations in the specificity and repeatability of detecting fold-changes in inputs. Nevertheless, FCD with specificity and repeatability by cells has been reported in the context of Drosophila wing development. Motivated by this fact and by extending previous FCD models, we here propose two possible mechanisms to achieve FCD with specificity and repeatability. One is the integrate-and-fire type: a system integrates the rate of temporal change in input and makes a response when the integrated value reaches a constant threshold, and this is followed by the reset of the integrated value. The other is the dynamic threshold type: a system response occurs when the input level reaches a threshold, whose value is multiplied by a certain constant after each response. These two mechanisms can be implemented biochemically by appropriately combining feed-forward and feedback loops. The main difference between the two models is their memory of input history; we discuss possible ways to distinguish between the two models experimentally.", "classifications": [ { "id": "Morishita", "label": "Group Morishita", "parent": "Morishita", "type": "group" }, { "id": "Morishita", "label": "Team Morishita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Ken-ichi", "last_name": "Hironaka", "name": null }, { "creator_type": "author", "first_name": "Yoshihiro", "last_name": "Morishita", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.bpj.2013.10.039" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "24411260" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cues", "descriptor_ui": "D003463", "major_topic": true }, { "descriptor": "Drosophila", "descriptor_ui": "D004330", "major_topic": false }, { "descriptor": "Feedback, Physiological", "descriptor_ui": "D025461", "major_topic": false }, { "descriptor": "Memory", "descriptor_ui": "D008568", "major_topic": false }, { "descriptor": "Models, Neurological", "descriptor_ui": "D008959", "major_topic": true }, { "descriptor": "Sensory Thresholds", "descriptor_ui": "D012684", "major_topic": true }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": true } ], "publication": { "conference_name": null, "date": "2014 Jan 07", "date_precision": "day", "issue": "1", "normalized_date": "2014-01-07", "pages": "279-288", "proceedings_title": null, "publisher": "", "title": "Biophysical Journal", "volume": "106", "year": 2014 }, "ssbd": { "database": [], "repository": [] }, "title": "Cellular Sensory Mechanisms for Detecting Specific Fold-Changes in Extracellular Cues.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The olfactory bulb (OB) is the first central processing center for olfactory information connecting with higher areas in the brain, and this neuronal circuitry mediates a variety of odor-evoked behavioral responses. In the adult mammalian brain, continuous neurogenesis occurs in two restricted regions, the subventricular zone (SVZ) of the lateral ventricle and the hippocampal dentate gyrus. New neurons born in the SVZ migrate through the rostral migratory stream and are integrated into the neuronal circuits of the OB throughout life. The significance of this continuous supply of new neurons in the OB has been implicated in plasticity and memory regulation. Two decades of huge investigation in adult neurogenesis revealed the biological importance of integration of new neurons into the olfactory circuits. In this review, we highlight the recent findings about the physiological functions of newly generated neurons in rodent OB circuits and then discuss the contribution of neurogenesis in the brain function. Finally, we introduce cutting edge technologies to monitor and manipulate the activity of new neurons.", "classifications": [ { "id": "Imayoshi", "label": "Group Imayoshi", "parent": "Imayoshi", "type": "group" }, { "id": "Imayoshi", "label": "Team Imayoshi", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Masayuki", "last_name": "Sakamoto", "name": null }, { "creator_type": "author", "first_name": "Ryoichiro", "last_name": "Kageyama", "name": null }, { "creator_type": "author", "first_name": "Itaru", "last_name": "Imayoshi", "name": null } ], "identifiers": { "doi": { "normalized": "10.3389/fnins.2014.00121" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "24904263" } }, "mesh": [], "publication": { "conference_name": null, "date": "2014", "date_precision": "year", "issue": "", "normalized_date": "2014", "pages": "", "proceedings_title": null, "publisher": "", "title": "Frontiers in Neuroscience", "volume": "8", "year": 2014 }, "ssbd": { "database": [], "repository": [] }, "title": "The functional significance of newly born neurons integrated into olfactory bulb circuits.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Neural crest cells (NCCs) are an embryonic migratory cell population with the ability to differentiate into a wide variety of cell types that contribute to the craniofacial skeleton, cornea, peripheral nervous system, and skin pigmentation. This ability suggests the promising role of NCCs as a source for cell-based therapy. Although several methods have been used to induce human NCCs (hNCCs) from human pluripotent stem cells (hPSCs), such as embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs), further modifications are required to improve the robustness, efficacy, and simplicity of these methods. Chemically defined medium (CDM) was used as the basal medium in the induction and maintenance steps. By optimizing the culture conditions, the combination of the GSK3beta inhibitor and TGFbeta inhibitor with a minimum growth factor (insulin) very efficiently induced hNCCs (70-80%) from hPSCs. The induced hNCCs expressed cranial NCC-related genes and stably proliferated in CDM supplemented with EGF and FGF2 up to at least 10 passages without changes being observed in the major gene expression profiles. Differentiation properties were confirmed for peripheral neurons, glia, melanocytes, and corneal endothelial cells. In addition, cells with differentiation characteristics similar to multipotent mesenchymal stromal cells (MSCs) were induced from hNCCs using CDM specific for human MSCs. Our simple and robust induction protocol using small molecule compounds with defined media enabled the generation of hNCCs as an intermediate material producing terminally differentiated cells for cell-based innovative medicine.", "classifications": [ { "id": "Yamamoto", "label": "Group Yamamoto", "parent": "Toyoshima", "type": "group" }, { "id": "Toyoshima", "label": "Team Toyoshima", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Makoto", "last_name": "Fukuta", "name": null }, { "creator_type": "author", "first_name": "Yoshinori", "last_name": "Nakai", "name": null }, { "creator_type": "author", "first_name": "Kosuke", "last_name": "Kirino", "name": null }, { "creator_type": "author", "first_name": "Masato", "last_name": "Nakagawa", "name": null }, { "creator_type": "author", "first_name": "Kazuya", "last_name": "Sekiguchi", "name": null }, { "creator_type": "author", "first_name": "Sanae", "last_name": "Nagata", "name": null }, { "creator_type": "author", "first_name": "Yoshihisa", "last_name": "Matsumoto", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Katsutsugu", "last_name": "Umeda", "name": null }, { "creator_type": "author", "first_name": "Toshio", "last_name": "Heike", "name": null }, { "creator_type": "author", "first_name": "Naoki", "last_name": "Okumura", "name": null }, { "creator_type": "author", "first_name": "Noriko", "last_name": "Koizumi", "name": null }, { "creator_type": "author", "first_name": "Takahiko", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Tatsutoshi", "last_name": "Nakahata", "name": null }, { "creator_type": "author", "first_name": "Megumu", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Takanobu", "last_name": "Otsuka", "name": null }, { "creator_type": "author", "first_name": "Shigeru", "last_name": "Kinoshita", "name": null }, { "creator_type": "author", "first_name": "Morio", "last_name": "Ueno", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Ikeya", "name": null }, { "creator_type": "author", "first_name": "Junya", "last_name": "Toguchida", "name": null } ], "identifiers": { "doi": { "normalized": "10.1371/journal.pone.0112291" }, "pmcid": { "normalized": "PMC4251837" }, "pmid": { "normalized": "25464501" } }, "mesh": [ { "descriptor": "Bone Morphogenetic Proteins", "descriptor_ui": "D019485", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Cell Lineage", "descriptor_ui": "D019070", "major_topic": false }, { "descriptor": "Cell Proliferation", "descriptor_ui": "D049109", "major_topic": false }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Chondrocytes", "descriptor_ui": "D019902", "major_topic": false }, { "descriptor": "Cornea", "descriptor_ui": "D003315", "major_topic": false }, { "descriptor": "Culture Media", "descriptor_ui": "D003470", "major_topic": false }, { "descriptor": "DNA, Complementary", "descriptor_ui": "D018076", "major_topic": false }, { "descriptor": "Embryonic Stem Cells", "descriptor_ui": "D053595", "major_topic": false }, { "descriptor": "Endothelial Cells", "descriptor_ui": "D042783", "major_topic": false }, { "descriptor": "Fibroblasts", "descriptor_ui": "D005347", "major_topic": false }, { "descriptor": "Flow Cytometry", "descriptor_ui": "D005434", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Induced Pluripotent Stem Cells", "descriptor_ui": "D057026", "major_topic": false }, { "descriptor": "Insulin", "descriptor_ui": "D007328", "major_topic": false }, { "descriptor": "Melanocytes", "descriptor_ui": "D008544", "major_topic": false }, { "descriptor": "Mesenchymal Stem Cells", "descriptor_ui": "D059630", "major_topic": false }, { "descriptor": "Neural Crest", "descriptor_ui": "D009432", "major_topic": false }, { "descriptor": "Oligonucleotide Array Sequence Analysis", "descriptor_ui": "D020411", "major_topic": false }, { "descriptor": "Osteogenesis", "descriptor_ui": "D010012", "major_topic": false }, { "descriptor": "Pluripotent Stem Cells", "descriptor_ui": "D039904", "major_topic": false }, { "descriptor": "Transforming Growth Factor beta", "descriptor_ui": "D016212", "major_topic": false } ], "publication": { "conference_name": null, "date": "2014", "date_precision": "year", "issue": "12", "normalized_date": "2014", "pages": "e112291", "proceedings_title": null, "publisher": "", "title": "PloS one", "volume": "9", "year": 2014 }, "ssbd": { "database": [], "repository": [] }, "title": "Derivation of mesenchymal stromal cells from pluripotent stem cells through a neural crest lineage using small molecule compounds with defined media.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Sialidase removes sialic acid from sialoglycoconjugates and plays crucial roles in many physiological and pathological processes. Various human cancers express an abnormally high level of the plasma membrane-associated sialidase isoform.Visualization of sialidase activity in living mammalian tissues would be useful not only for understanding sialidase functions but also for cancer diagnosis. However, since enzyme activity of mammalian sialidase is remarkably weak compared with that of bacterial and viral sialidases, it has been difficult to detect sialidase activity in mammalian tissues. We synthesized a novel benzothiazolylphenol-based sialic acid derivative (BTP-Neu5Ac) as a fluorescent sialidase substrate. BTP-Neu5Ac can visualize sialidase activities sensitively and selectively in acute rat brain slices. Cancer cells implanted orthotopically in mouse colons and human colon cancers (stages T3-T4) were also clearly detected with BTP-Neu5Ac. The results suggest that BTP-Neu5Ac is useful for histochemical imaging of sialidase activities.", "classifications": [ { "id": "Suzuki", "label": "Group Suzuki", "parent": "Takekawa", "type": "group" }, { "id": "Takekawa", "label": "Team Takekawa", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Akira", "last_name": "Minami", "name": null }, { "creator_type": "author", "first_name": "Tadamune", "last_name": "Otsubo", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Ieno", "name": null }, { "creator_type": "author", "first_name": "Kiyoshi", "last_name": "Ikeda", "name": null }, { "creator_type": "author", "first_name": "Hiroaki", "last_name": "Kanazawa", "name": null }, { "creator_type": "author", "first_name": "Kosuke", "last_name": "Shimizu", "name": null }, { "creator_type": "author", "first_name": "Ko", "last_name": "Ohata", "name": null }, { "creator_type": "author", "first_name": "Tsunehiro", "last_name": "Yokochi", "name": null }, { "creator_type": "author", "first_name": "Yuuki", "last_name": "Horii", "name": null }, { "creator_type": "author", "first_name": "Hokuto", "last_name": "Fukumoto", "name": null }, { "creator_type": "author", "first_name": "Risa", "last_name": "Taguchi", "name": null }, { "creator_type": "author", "first_name": "Tadanobu", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Naoto", "last_name": "Oku", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Suzuki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1371/journal.pone.0081941" }, "pmcid": { "normalized": "PMC3888388" }, "pmid": { "normalized": "24427265" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Bacteria", "descriptor_ui": "D001419", "major_topic": false }, { "descriptor": "Brain", "descriptor_ui": "D001921", "major_topic": false }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Enzyme Activation", "descriptor_ui": "D004789", "major_topic": false }, { "descriptor": "Fluorescent Dyes", "descriptor_ui": "D005456", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Hydrolysis", "descriptor_ui": "D006868", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mammals", "descriptor_ui": "D008322", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Molecular Imaging", "descriptor_ui": "D057054", "major_topic": false }, { "descriptor": "Neoplasms", "descriptor_ui": "D009369", "major_topic": false }, { "descriptor": "Neuraminidase", "descriptor_ui": "D009439", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Substrate Specificity", "descriptor_ui": "D013379", "major_topic": false } ], "publication": { "conference_name": null, "date": "2014", "date_precision": "year", "issue": "1", "normalized_date": "2014", "pages": "e81941", "proceedings_title": null, "publisher": "", "title": "PloS one", "volume": "9", "year": 2014 }, "ssbd": { "database": [], "repository": [] }, "title": "Visualization of sialidase activity in Mammalian tissues and cancer detection with a novel fluorescent sialidase substrate.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Background: Directed cell migration is essential for normal development. In most of the migratory cell populations that have been analyzed in detail to date, all of the cells migrate as a collective from one location to another. However, there are also migratory cell populations that must populate the areas through which they migrate, and thus some cells get left behind while others advance. Very little is known about how individual cells behave to achieve concomitant directional migration and population of the migratory route. We examined the behavior of enteric neural crest-derived cells (ENCCs), which must both advance caudally to reach the anal end and populate each gut region. Results: The behavior of individual ENCCs was examined using live imaging and mice in which ENCCs express a photoconvertible protein. We show that individual ENCCs exhibit very variable directionalities and speed; as the migratory wavefront of ENCCs advances caudally, each gut region is populated primarily by some ENCCs migrating non-directionally. After populating each region, ENCCs remain migratory for at least 24 hours. Endothelin receptor type B (EDNRB) signaling is known to be essential for the normal advance of the ENCC population. We now show that perturbation of EDNRB principally affects individual ENCC speed rather than directionality. The trajectories of solitary ENCCs, which occur transiently at the wavefront, were consistent with an unbiased random walk and so cell-cell contact is essential for directional migration. ENCCs migrate in close association with neurites. We showed that although ENCCs often use neurites as substrates, ENCCs lead the way, neurites are not required for chain formation and neurite growth is more directional than the migration of ENCCs as a whole. Conclusions: Each gut region is initially populated by sub-populations of ENCCs migrating non-directionally, rather than stopping. This might provide a mechanism for ensuring a uniform density of ENCCs along the growing gut.", "classifications": [ { "id": "Enomoto", "label": "Group Enomoto", "parent": "Enomoto", "type": "group" }, { "id": "Enomoto", "label": "Team Enomoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Heather M.", "last_name": "Young", "name": null }, { "creator_type": "author", "first_name": "Annette J.", "last_name": "Bergner", "name": null }, { "creator_type": "author", "first_name": "Matthew J.", "last_name": "Simpson", "name": null }, { "creator_type": "author", "first_name": "Sonja J.", "last_name": "McKeown", "name": null }, { "creator_type": "author", "first_name": "Marlene M.", "last_name": "Hao", "name": null }, { "creator_type": "author", "first_name": "Colin R.", "last_name": "Anderson", "name": null }, { "creator_type": "author", "first_name": "Hideki", "last_name": "Enomoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1186/1741-7007-12-23" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "24670214" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Adhesion", "descriptor_ui": "D002448", "major_topic": false }, { "descriptor": "Cell Communication", "descriptor_ui": "D002450", "major_topic": false }, { "descriptor": "Cell Movement", "descriptor_ui": "D002465", "major_topic": true }, { "descriptor": "Cell Shape", "descriptor_ui": "D048430", "major_topic": false }, { "descriptor": "Enteric Nervous System", "descriptor_ui": "D017615", "major_topic": false }, { "descriptor": "Gastrointestinal Tract", "descriptor_ui": "D041981", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Neural Crest", "descriptor_ui": "D009432", "major_topic": false }, { "descriptor": "Neurites", "descriptor_ui": "D016501", "major_topic": false }, { "descriptor": "Pseudopodia", "descriptor_ui": "D011554", "major_topic": false }, { "descriptor": "Receptor, Endothelin B", "descriptor_ui": "D044023", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false } ], "publication": { "conference_name": null, "date": "2014", "date_precision": "year", "issue": "", "normalized_date": "2014", "pages": "23", "proceedings_title": null, "publisher": "", "title": "BMC Biology", "volume": "12", "year": 2014 }, "ssbd": { "database": [], "repository": [] }, "title": "Colonizing while migrating: how do individual enteric neural crest cells behave?", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Cardiac redox homeostasis is precisely regulated by reactive oxygen species (ROS) or electrophilic molecules that are formed by ROS reacting with intracellular substrates, and their eliminating systems. We have focused on the role of nitric oxide (NO) generated from inducible NO synthase (iNOS) that is continuously upregulated from early stage of heart failure, and revealed that iNOS-derived NO acts as a protective factor in the early stage of heart failure, whereas it contributes to induction of cardiac early senescence in later stages. The switching mechanism of NO-mediated signaling includes formation of endogenous NO-derived electrophilic byproducts such as 8-nitroguanosine 3',5'-cyclic monophosphate (8-nitro-cGMP), which selectively targets an oncogenic small GTPase H-Ras at Cys-184, leading to cardiac cell senescence via covalent modification (S-guanylation) and activation of H-Ras. We also found that hydrogen sulfide-related reactive sulfur species (RSS) function as potent nucleophiles to eliminate electrophilic modification of H-Ras and suppress the onset of chronic heart failure after myocardial infarction. Our results strongly suggest a new concept of redox biology in which suppression of electrophilic irreversible modification of protein cysteine thiols by RSS may be a new therapeutic strategy of cardiovascular diseases.", "classifications": [ { "id": "Nishida", "label": "Group Nishida", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Motohiro", "last_name": "Nishida", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Toyama", "name": null }, { "creator_type": "author", "first_name": "Yoshito", "last_name": "Kumagai", "name": null }, { "creator_type": "author", "first_name": "Takuro", "last_name": "Numaga-Tomita", "name": null } ], "identifiers": { "doi": { "normalized": "10.1248/yakushi.14-00209-1" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "25452233" } }, "mesh": [ { "descriptor": "Aging", "descriptor_ui": "D000375", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Free Radicals", "descriptor_ui": "D005609", "major_topic": false }, { "descriptor": "Heart Failure", "descriptor_ui": "D006333", "major_topic": false }, { "descriptor": "Homeostasis", "descriptor_ui": "D006706", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Oxidation-Reduction", "descriptor_ui": "D010084", "major_topic": false }, { "descriptor": "Sulfur", "descriptor_ui": "D013455", "major_topic": false } ], "publication": { "conference_name": null, "date": "2014", "date_precision": "year", "issue": "12", "normalized_date": "2014", "pages": "1239-1243", "proceedings_title": null, "publisher": "", "title": "Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan", "volume": "134", "year": 2014 }, "ssbd": { "database": [], "repository": [] }, "title": "[Establishment of a novel therapeutic strategy for heart failure based on the mechanism underlying maintenance of redox homeostasis by reactive sulfur species].", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The tyrosine kinase c-Src is upregulated in numerous human cancers, implying a role for c-Src in cancer progression. Previously, we have shown that sequestration of activated c-Src into lipid rafts via a transmembrane adaptor, Cbp/PAG1, efficiently suppresses c-Src-induced cell transformation in Csk-deficient cells, suggesting that the transforming activity of c-Src is spatially regulated via Cbp in lipid rafts. To dissect the molecular mechanisms of the Cbp-mediated regulation of c-Src, a combined analysis was performed that included mathematical modeling and in vitro experiments in a c-Src- or Cbp-inducible system. c-Src activity was first determined as a function of c-Src or Cbp levels, using focal adhesion kinase (FAK) as a crucial c-Src substrate. Based on these experimental data, two mathematical models were constructed, the sequestration model and the ternary model. The computational analysis showed that both models supported our proposal that raft localization of Cbp is crucial for the suppression of c-Src function, but the ternary model, which includes a ternary complex consisting of Cbp, c-Src, and FAK, also predicted that c-Src function is dependent on the lipid-raft volume. Experimental analysis revealed that c-Src activity is elevated when lipid rafts are disrupted and the ternary complex forms in non-raft membranes, indicating that the ternary model accurately represents the system. Moreover, the ternary model predicted that, if Cbp enhances the interaction between c-Src and FAK, Cbp could promote c-Src function when lipid rafts are disrupted. These findings underscore the crucial role of lipid rafts in the Cbp-mediated negative regulation of c-Src-transforming activity, and explain the positive role of Cbp in c-Src regulation under particular conditions where lipid rafts are perturbed.", "classifications": [ { "id": "Suzuki", "label": "Group Suzuki", "parent": "Takekawa", "type": "group" }, { "id": "Takekawa", "label": "Team Takekawa", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Takashi", "last_name": "Saitou", "name": null }, { "creator_type": "author", "first_name": "Kentaro", "last_name": "Kajiwara", "name": null }, { "creator_type": "author", "first_name": "Chitose", "last_name": "Oneyama", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Masato", "last_name": "Okada", "name": null } ], "identifiers": { "doi": { "normalized": "10.1371/journal.pone.0093470" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "24675741" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "CSK Tyrosine-Protein Kinase", "descriptor_ui": "D000081247", "major_topic": false }, { "descriptor": "Embryo, Mammalian", "descriptor_ui": "D004622", "major_topic": false }, { "descriptor": "Fibroblasts", "descriptor_ui": "D005347", "major_topic": false }, { "descriptor": "Focal Adhesion Kinase 1", "descriptor_ui": "D051417", "major_topic": false }, { "descriptor": "Gene Deletion", "descriptor_ui": "D017353", "major_topic": false }, { "descriptor": "Gene Expression Regulation", "descriptor_ui": "D005786", "major_topic": false }, { "descriptor": "Kinetics", "descriptor_ui": "D007700", "major_topic": false }, { "descriptor": "Membrane Microdomains", "descriptor_ui": "D021962", "major_topic": false }, { "descriptor": "Membrane Proteins", "descriptor_ui": "D008565", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Models, Statistical", "descriptor_ui": "D015233", "major_topic": true }, { "descriptor": "Phosphoproteins", "descriptor_ui": "D010750", "major_topic": false }, { "descriptor": "Protein Binding", "descriptor_ui": "D011485", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "src-Family Kinases", "descriptor_ui": "D019061", "major_topic": false } ], "publication": { "conference_name": null, "date": "2014", "date_precision": "year", "issue": "3", "normalized_date": "2014", "pages": "", "proceedings_title": null, "publisher": "", "title": "PLoS ONE", "volume": "9", "year": 2014 }, "ssbd": { "database": [], "repository": [] }, "title": "Roles of Raft-Anchored Adaptor Cbp/PAG1 in Spatial Regulation of c-Src Kinase.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Recent studies have shown that the behavior of calcium in the epidermis is closely related to the conditions of the skin, especially the differentiation of the epidermal keratinocytes and the permeability barrier function, and therefore a correct understanding of the calcium dynamics is important in explaining epidermal homeostasis. Here we report on experimental observations of in vitro calcium waves in keratinocytes induced by mechanical stimulation, and present a mathematical model that can describe the experimentally observed wave behavior that includes finite-range wave propagation and a ring-shaped pattern. A mechanism of the ring formation hypothesized by our model may be related to similar calcium propagation patterns observed during the wound healing process in the epidermis. We discuss a possible extension of our model that may serve as a tool for investigating the mechanisms of various skin diseases.", "classifications": [ { "id": "Nagayama", "label": "Group Nagayama", "parent": "Fujiwara", "type": "group" }, { "id": "Fujiwara", "label": "Team Fujiwara", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yasuaki", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Yumi", "last_name": "Sanno", "name": null }, { "creator_type": "author", "first_name": "Akihiko", "last_name": "Sakai", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Sawabu", "name": null }, { "creator_type": "author", "first_name": "Moe", "last_name": "Tsutsumi", "name": null }, { "creator_type": "author", "first_name": "Makiko", "last_name": "Goto", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Kitahata", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Nakata", "name": null }, { "creator_type": "author", "first_name": "Junichi", "last_name": "Kumamoto", "name": null }, { "creator_type": "author", "first_name": "Mitsuhiro", "last_name": "Denda", "name": null }, { "creator_type": "author", "first_name": "Masaharu", "last_name": "Nagayama", "name": null } ], "identifiers": { "doi": { "normalized": "10.1371/journal.pone.0092650" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "24663805" } }, "mesh": [ { "descriptor": "Adenosine Triphosphate", "descriptor_ui": "D000255", "major_topic": false }, { "descriptor": "Biomechanical Phenomena", "descriptor_ui": "D001696", "major_topic": false }, { "descriptor": "Calcium Signaling", "descriptor_ui": "D020013", "major_topic": true }, { "descriptor": "Epidermal Cells", "descriptor_ui": "D000078404", "major_topic": false }, { "descriptor": "Gap Junctions", "descriptor_ui": "D017629", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Keratinocytes", "descriptor_ui": "D015603", "major_topic": false }, { "descriptor": "Mechanical Phenomena", "descriptor_ui": "D055595", "major_topic": true }, { "descriptor": "Models, Biological", "descriptor_ui": "D008954", "major_topic": true } ], "publication": { "conference_name": null, "date": "2014", "date_precision": "year", "issue": "3", "normalized_date": "2014", "pages": "", "proceedings_title": null, "publisher": "", "title": "PLoS ONE", "volume": "9", "year": 2014 }, "ssbd": { "database": [], "repository": [] }, "title": "Mathematical Modeling of Calcium Waves Induced by Mechanical Stimulation in Keratinocytes.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Androgen receptor is a primary transcription factor involved in the proliferation of prostate cancer cells. Thus, hormone therapy using antiandrogens, such as bicalutamide, is a first-line treatment for the disease. Although hormone therapy initially reduces the tumor burden, many patients eventually relapse, developing tumors with acquired endocrine resistance. Elucidation of the molecular mechanisms underlying endocrine resistance is therefore a fundamental issue for the understanding and development of alternative therapeutics for advanced prostate cancer. In the present study, we performed short hairpin RNA (shRNA)-mediated functional screening to identify genes involved in bicalutamide-mediated effects on LNCaP prostate cancer cells. Among such candidate genes selected by screening using volcano plot analysis, ribosomal protein L31 (RPL31) was found to be essential for cell proliferation and cell-cycle progression in bicalutamide-resistant LNCaP (BicR) cells, based on small interfering RNA (siRNA)-mediated knockdown experiments. Of note, RPL31 mRNA is more abundantly expressed in BicR cells than in parental LNCaP cells, and clinical data from ONCOMINE and The Cancer Genome Altas showed that RPL31 is overexpressed in prostate carcinomas compared with benign prostate tissues. Intriguingly, protein levels of the tumor suppressor p53 and its targets, p21 and MDM2, were increased in LNCaP and BicR cells treated with RPL31 siRNA. We observed decreased degradation of p53 protein after RPL31 knockdown. Moreover, the suppression of growth and cell cycle upon RPL31 knockdown was partially recovered with p53 siRNA treatment. These results suggest that RPL31 is involved in bicalutamide-resistant growth of prostate cancer cells. The shRNA-mediated functional screen in this study provides new insight into the molecular mechanisms and therapeutic targets of advanced prostate cancer.", "classifications": [ { "id": "Okamoto", "label": "Group Okamoto", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yojiro", "last_name": "Maruyama", "name": null }, { "creator_type": "author", "first_name": "Toshiaki", "last_name": "Miyazaki", "name": null }, { "creator_type": "author", "first_name": "Kazuhiro", "last_name": "Ikeda", "name": null }, { "creator_type": "author", "first_name": "Toshiyuki", "last_name": "Okumura", "name": null }, { "creator_type": "author", "first_name": "Wataru", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Kuniko", "last_name": "Horie-Inoue", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Okamoto", "name": null }, { "creator_type": "author", "first_name": "Satoru", "last_name": "Takeda", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Inoue", "name": null } ], "identifiers": { "doi": { "normalized": "10.1371/journal.pone.0108743" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "25285958" } }, "mesh": [ { "descriptor": "Anilides", "descriptor_ui": "D000813", "major_topic": false }, { "descriptor": "Cell Cycle", "descriptor_ui": "D002453", "major_topic": false }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Cell Proliferation", "descriptor_ui": "D049109", "major_topic": false }, { "descriptor": "Drug Resistance, Neoplasm", "descriptor_ui": "D019008", "major_topic": false }, { "descriptor": "Genes, Neoplasm", "descriptor_ui": "D052138", "major_topic": false }, { "descriptor": "Genetic Association Studies", "descriptor_ui": "D056726", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Nitriles", "descriptor_ui": "D009570", "major_topic": false }, { "descriptor": "Prostatic Neoplasms", "descriptor_ui": "D011471", "major_topic": false }, { "descriptor": "Proteolysis", "descriptor_ui": "D059748", "major_topic": false }, { "descriptor": "Proto-Oncogene Proteins c-mdm2", "descriptor_ui": "D051736", "major_topic": false }, { "descriptor": "Reproducibility of Results", "descriptor_ui": "D015203", "major_topic": false }, { "descriptor": "Ribosomal Proteins", "descriptor_ui": "D012269", "major_topic": false }, { "descriptor": "RNA, Small Interfering", "descriptor_ui": "D034741", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Tosyl Compounds", "descriptor_ui": "D014105", "major_topic": false }, { "descriptor": "Tumor Suppressor Protein p53", "descriptor_ui": "D016159", "major_topic": false }, { "descriptor": "Up-Regulation", "descriptor_ui": "D015854", "major_topic": false } ], "publication": { "conference_name": null, "date": "2014", "date_precision": "year", "issue": "10", "normalized_date": "2014", "pages": "", "proceedings_title": null, "publisher": "", "title": "PLoS ONE", "volume": "9", "year": 2014 }, "ssbd": { "database": [], "repository": [] }, "title": "Short Hairpin RNA Library-Based Functional Screening Identified Ribosomal Protein L31 That Modulates Prostate Cancer Cell Growth via p53 Pathway.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Gastrointestinal symptoms are a common manifestation of adverse drug effects. Non-steroid anti-inflammatory drugs (NSAIDs) are widely prescribed drugs that induce the serious side effect of gastric mucosal ulceration. Biomarkers for these side effects have not been identified and ulcers are now only detectable by endoscopy. We previously identified five metabolites as biomarker candidates for NSAID-induced gastric ulcer using capillary electrophoresis-mass spectrometry (CE-MS)-based metabolomic analysis of serum and stomach from rats. Here, to clarify mechanism of changes and limitations of indications of biomarker candidates, we performed CE-MS-based metabolomic profiling in stomach and serum from rats with gastric ulcers induced by ethanol, stress, and aspirin. The results suggest that a decrease in hydroxyproline reflects the induction of gastric injury and may be useful in identifying gastric ulcer induced by multiple causes. While extrapolation to humans requires further study, hydroxyproline can be a new serum biomarker of gastric injury regardless of cause.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Kenichiro", "last_name": "Takeuchi", "name": null }, { "creator_type": "author", "first_name": "Maki", "last_name": "Ohishi", "name": null }, { "creator_type": "author", "first_name": "Keiko", "last_name": "Endo", "name": null }, { "creator_type": "author", "first_name": "Kenichi", "last_name": "Suzumura", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Naraoka", "name": null }, { "creator_type": "author", "first_name": "Takeji", "last_name": "Ohata", "name": null }, { "creator_type": "author", "first_name": "Jiro", "last_name": "Seki", "name": null }, { "creator_type": "author", "first_name": "Yoichi", "last_name": "Miyamae", "name": null }, { "creator_type": "author", "first_name": "Masashi", "last_name": "Honma", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null } ], "identifiers": { "doi": { "normalized": "10.4137/bmi.s15918" }, "pmcid": { "normalized": "PMC4125369" }, "pmid": { "normalized": "25125970" } }, "mesh": [], "publication": { "conference_name": null, "date": "2014", "date_precision": "year", "issue": "", "normalized_date": "2014", "pages": "61-66", "proceedings_title": null, "publisher": "", "title": "Biomarker insights", "volume": "9", "year": 2014 }, "ssbd": { "database": [], "repository": [] }, "title": "Hydroxyproline, a serum biomarker candidate for gastric ulcer in rats: a comparison study of metabolic analysis of gastric ulcer models induced by ethanol, stress, and aspirin.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Comparative whole-genome sequencing enables the identification of specific mutations during adaptation of bacteria to new environments and allelic replacement can establish their causality. However, the mechanisms of action are hard to decipher and little has been achieved for epistatic mutations, especially at the metabolic level. Here we show that a strain of Escherichia coli carrying mutations in the rpoC and glpK genes, derived from adaptation in glycerol, uses two distinct metabolic strategies to gain growth advantage. A 27-bp deletion in the rpoC gene first increases metabolic efficiency. Then, a point mutation in the glpK gene promotes growth by improving glycerol utilization but results in increased carbon wasting as overflow metabolism. In a strain carrying both mutations, these contrasting carbon/energy saving and wasting mechanisms work together to give an 89% increase in growth rate. This study provides insight into metabolic reprogramming during adaptive laboratory evolution for fast cellular growth.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Kian-Kai", "last_name": "Cheng", "name": null }, { "creator_type": "author", "first_name": "Baek-Seok", "last_name": "Lee", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Masuda", "name": null }, { "creator_type": "author", "first_name": "Takuro", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Kazutaka", "last_name": "Ikeda", "name": null }, { "creator_type": "author", "first_name": "Akiyoshi", "last_name": "Hirayama", "name": null }, { "creator_type": "author", "first_name": "Lingli", "last_name": "Deng", "name": null }, { "creator_type": "author", "first_name": "Jiyang", "last_name": "Dong", "name": null }, { "creator_type": "author", "first_name": "Kazuyuki", "last_name": "Shimizu", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Masaru", "last_name": "Tomita", "name": null }, { "creator_type": "author", "first_name": "Bernhard O.", "last_name": "Palsson", "name": null }, { "creator_type": "author", "first_name": "Martin", "last_name": "Robert", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/ncomms4233" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "24481126" } }, "mesh": [ { "descriptor": "Adaptation, Biological", "descriptor_ui": "D000220", "major_topic": true }, { "descriptor": "Biomass", "descriptor_ui": "D018533", "major_topic": false }, { "descriptor": "DNA-Directed RNA Polymerases", "descriptor_ui": "D012321", "major_topic": false }, { "descriptor": "Escherichia coli", "descriptor_ui": "D004926", "major_topic": false }, { "descriptor": "Escherichia coli Proteins", "descriptor_ui": "D029968", "major_topic": false }, { "descriptor": "Glycerol", "descriptor_ui": "D005990", "major_topic": false }, { "descriptor": "Glycerol Kinase", "descriptor_ui": "D005991", "major_topic": false }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": false } ], "publication": { "conference_name": null, "date": "2014", "date_precision": "year", "issue": "", "normalized_date": "2014", "pages": "3233", "proceedings_title": null, "publisher": "", "title": "Nature communications", "volume": "5", "year": 2014 }, "ssbd": { "database": [], "repository": [] }, "title": "Global metabolic network reorganization by adaptive mutations allows fast growth of Escherichia coli on glycerol.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Lysine methylation has been extensively studied in histones, where it has been shown to provide specific epigenetic marks for the regulation of gene expression; however, the molecular mechanism and physiological function of lysine methylation in proteins other than histones remains to be fully addressed. To better understand the substrate diversity of lysine methylation, S-adenosylmethionine (SAM) derivatives with alkyne-moieties have been synthesized. A selenium-based SAM analog, propargylic Se-adenosyl-l-selenomethionine (ProSeAM), has a wide spectrum of reactivity against various lysine methyltransferases (KMTs) with sufficient stability to support enzymatic reactions in vitro. By using ProSeAM as a chemical probe for lysine methylation, we identified substrates for two seven-beta-strand KMTs, METTL21A and METTL10, on a proteomic scale in mammalian cells. METTL21A has been characterized as a heat shock protein (HSP)-70 methyltransferase. Mammalian METTL10 remains functionally uncharacterized, although its ortholog in yeast, See1, has been shown to methylate the translation elongation factor eEF1A. By using ProSeAM-mediated alkylation followed by purification and quantitative MS analysis, we confirmed that METTL21A labels HSP70 family proteins. Furthermore, we demonstrated that METTL10 also methylates the eukaryotic elongation factor EF1A1 in mammalian cells. Subsequent biochemical characterization revealed that METTL10 specifically trimethylates EF1A1 at lysine 318 and that siRNA-mediated knockdown of METTL10 decreases EF1A1 methylation levels in vivo. Thus, our study emphasizes the utility of the synthetic cofactor ProSeAM as a chemical probe for the identification of non-histone substrates of KMTs.", "classifications": [ { "id": "Sodeoka", "label": "Group Sodeoka", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Tadahiro", "last_name": "Shimazu", "name": null }, { "creator_type": "author", "first_name": "Joaquin", "last_name": "Barjau", "name": null }, { "creator_type": "author", "first_name": "Yoshihiro", "last_name": "Sohtome", "name": null }, { "creator_type": "author", "first_name": "Mikiko", "last_name": "Sodeoka", "name": null }, { "creator_type": "author", "first_name": "Yoichi", "last_name": "Shinkai", "name": null } ], "identifiers": { "doi": { "normalized": "10.1371/journal.pone.0105394" }, "pmcid": { "normalized": "PMC4140779" }, "pmid": { "normalized": "25144183" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "HEK293 Cells", "descriptor_ui": "D057809", "major_topic": false }, { "descriptor": "Histone-Lysine N-Methyltransferase", "descriptor_ui": "D011495", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Microscopy, Fluorescence", "descriptor_ui": "D008856", "major_topic": false }, { "descriptor": "S-Adenosylmethionine", "descriptor_ui": "D012436", "major_topic": false }, { "descriptor": "Selenium", "descriptor_ui": "D012643", "major_topic": false }, { "descriptor": "Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization", "descriptor_ui": "D019032", "major_topic": false } ], "publication": { "conference_name": null, "date": "2014", "date_precision": "year", "issue": "8", "normalized_date": "2014", "pages": "e105394", "proceedings_title": null, "publisher": "", "title": "PloS one", "volume": "9", "year": 2014 }, "ssbd": { "database": [], "repository": [] }, "title": "Selenium-based S-adenosylmethionine analog reveals the mammalian seven-beta-strand methyltransferase METTL10 to be an EF1A1 lysine methyltransferase.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "System level understanding of the cell requires detailed description of the cell state, which is often characterized by the expression levels of proteins. However, understanding the cell state requires comprehensive information of the cell, which is usually obtained from a large number of cells and their disruption. In this study, we used Raman spectroscopy, which can report changes in the cell state without introducing any label, as a non-invasive method with single cell capability. Significant differences in Raman spectra were observed at the levels of both the cytosol and nucleus in different cell-lines from mouse, indicating that Raman spectra reflect differences in the cell state. Difference in cell state was observed before and after the induction of differentiation in neuroblastoma and adipocytes, showing that Raman spectra can detect subtle changes in the cell state. Cell state transitions during embryonic stem cell (ESC) differentiation were visualized when Raman spectroscopy was coupled with principal component analysis (PCA), which showed gradual transition in the cell states during differentiation. Detailed analysis showed that the diversity between cells are large in undifferentiated ESC and in mesenchymal stem cells compared with terminally differentiated cells, implying that the cell state in stem cells stochastically fluctuates during the self-renewal process. The present study strongly indicates that Raman spectral morphology, in combination with PCA, can be used to establish cells' fingerprints, which can be useful for distinguishing and identifying different cellular states.", "classifications": [ { "id": "Fujita", "label": "Group Fujita", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Taro", "last_name": "Ichimura", "name": null }, { "creator_type": "author", "first_name": "Liang-da", "last_name": "Chiu", "name": null }, { "creator_type": "author", "first_name": "Katsumasa", "last_name": "Fujita", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Kawata", "name": null }, { "creator_type": "author", "first_name": "Tomonobu M.", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Toshio", "last_name": "Yanagida", "name": null }, { "creator_type": "author", "first_name": "Hideaki", "last_name": "Fujita", "name": null } ], "identifiers": { "doi": { "normalized": "10.1371/journal.pone.0084478" }, "pmcid": { "normalized": "PMC3883674" }, "pmid": { "normalized": "24409302" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "Embryonic Stem Cells", "descriptor_ui": "D053595", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Spectrum Analysis, Raman", "descriptor_ui": "D013059", "major_topic": false } ], "publication": { "conference_name": null, "date": "2014", "date_precision": "year", "issue": "1", "normalized_date": "2014", "pages": "e84478", "proceedings_title": null, "publisher": "", "title": "PloS one", "volume": "9", "year": 2014 }, "ssbd": { "database": [], "repository": [] }, "title": "Visualizing cell state transition using Raman spectroscopy.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Background: Chronic kidney disease (CKD) is known to be one of the causes of cardiovascular disease and end-stage renal disease. Among the several treatable risk factors of CKD, that of dyslipidemia is relatively controversial. To clarify the association of polymorphisms in genes involved in lipid metabolism with the risk of CKD in the Japanese population, we used cross-sectional data from the Japan Multi-Institutional Collaborative Cohort (J-MICC) Study. Methods: A total of 3,268 men and women, aged 35–69 years, were selected from J-MICC Study participants for inclusion in this study. Twenty-eight candidate single nucleotide polymorphisms (SNPs) were selected in 17 genes associated with the risk of lipid metabolism disorders, and genotyping of the subjects was conducted using the multiplex PCR-based invader assay. The prevalence of CKD was determined for stages 3–5 (defined as estimated glomerular filtration rate <60 ml/min/1.73 m2). Results: Logistic regression analysis revealed that SNPs APOA5 T − 1131C (rs662799), APOA5 T1259C (rs2266788), TOMM40 A/G (rs157580), and CETP TaqIB (rs708272) were significantly associated with CKD risk in those individuals genotyped, with age- and sex-adjusted odds ratios (ORs) per minor allele (and 95% confidence intervals (CIs)) of OR 1.22 (95% CI: 1.06–1.39), 1.19 (1.03–1.37), 1.27 (1.12–1.45), and 0.81 (0.71–0.92), respectively. Analysis of the gene–environment interaction revealed that body mass index (BMI) was a significant effect modifier for APOA5 T − 1131C (rs662799) and a marginally significant effect modifier for APOA5 T/C (rs2266788), with the interaction between BMI ≥30 and individuals with at least one minor allele of each genotype of OR 10.43 (95% CI: 1.29–84.19) and 3.36 (0.87–13.01), respectively. Conclusions: Four polymorphisms in APOA5, TOMM40, and CETP were shown to be significantly associated with CKD risk, and a significant interaction between the two APOA5 SNPs and BMI on CKD risk was also demonstrated. This suggests the future possibility of personalized risk estimation for this life-limiting disease. Electronic supplementary material: The online version of this article (doi:10.1186/1476-511X-13-162) contains supplementary material, which is available to authorized users.", "classifications": [ { "id": "Tanaka", "label": "Group Tanaka", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Asahi", "last_name": "Hishida", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Wakai", "name": null }, { "creator_type": "author", "first_name": "Mariko", "last_name": "Naito", "name": null }, { "creator_type": "author", "first_name": "Shino", "last_name": "Suma", "name": null }, { "creator_type": "author", "first_name": "Tae", "last_name": "Sasakabe", "name": null }, { "creator_type": "author", "first_name": "Nobuyuki", "last_name": "Hamajima", "name": null }, { "creator_type": "author", "first_name": "Satoyo", "last_name": "Hosono", "name": null }, { "creator_type": "author", "first_name": "Mikako", "last_name": "Horita", "name": null }, { "creator_type": "author", "first_name": "Tanvir Chowdhury", "last_name": "Turin", "name": null }, { "creator_type": "author", "first_name": "Sadao", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Tara Sefanya", "last_name": "Kairupan", "name": null }, { "creator_type": "author", "first_name": "Haruo", "last_name": "Mikami", "name": null }, { "creator_type": "author", "first_name": "Keizo", "last_name": "Ohnaka", "name": null }, { "creator_type": "author", "first_name": "Isao", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Hirokazu", "last_name": "Uemura", "name": null }, { "creator_type": "author", "first_name": "Michiaki", "last_name": "Kubo", "name": null }, { "creator_type": "author", "first_name": "Hideo", "last_name": "Tanaka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1186/1476-511x-13-162" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "25311932" } }, "mesh": [ { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Apolipoprotein A-V", "descriptor_ui": "D000072040", "major_topic": false }, { "descriptor": "Apolipoproteins A", "descriptor_ui": "D001054", "major_topic": false }, { "descriptor": "Body Mass Index", "descriptor_ui": "D015992", "major_topic": false }, { "descriptor": "Cross-Sectional Studies", "descriptor_ui": "D003430", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Gene Frequency", "descriptor_ui": "D005787", "major_topic": false }, { "descriptor": "Genetic Association Studies", "descriptor_ui": "D056726", "major_topic": false }, { "descriptor": "Genetic Predisposition to Disease", "descriptor_ui": "D020022", "major_topic": false }, { "descriptor": "Glomerular Filtration Rate", "descriptor_ui": "D005919", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Japan", "descriptor_ui": "D007564", "major_topic": false }, { "descriptor": "Linkage Disequilibrium", "descriptor_ui": "D015810", "major_topic": false }, { "descriptor": "Lipid Metabolism", "descriptor_ui": "D050356", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Polymorphism, Single Nucleotide", "descriptor_ui": "D020641", "major_topic": true }, { "descriptor": "Renal Insufficiency, Chronic", "descriptor_ui": "D051436", "major_topic": false }, { "descriptor": "Risk Factors", "descriptor_ui": "D012307", "major_topic": false } ], "publication": { "conference_name": null, "date": "2014", "date_precision": "year", "issue": "", "normalized_date": "2014", "pages": "", "proceedings_title": null, "publisher": "", "title": "Lipids in Health and Disease", "volume": "13", "year": 2014 }, "ssbd": { "database": [], "repository": [] }, "title": "Polymorphisms of genes involved in lipid metabolism and risk of chronic kidney disease in Japanese - cross-sectional data from the J-MICC study.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Background: Kawasaki Disease (KD) involves a diffuse and systemic vasculitis of unknown etiology that mainly affects infants and children. Although a considerable number of analyses of the clinical, histopathological and molecular biological details underlying the mechanism responsible for the development of coronary arterial lesions, it is still poorly understood.The purpose of this study was to analyze the state of angiogenesis, vasculogenesis and the distribution of blood vessels using an animal model of KD like vasculitis. We investigated the involvement of the vasa vasorum from the adventitia in the vascular involvement and the development of the disease state by performing sequential histopathology, scanning electron microscopy (SEM) and micro computed tomography (CT) studies using a murine model of vasculitis induced by the Candida albicans water-soluble fraction (CAWS). Methods: To prepare the animal model of KD like vasculitis, CAWS was intraperitoneally injected into C57BL/6N mice for five consecutive days as reported by Ohno et al. We observed the changes of the vasa vasorum at the aorta and the orifices of the coronary arteries by SEM and micro CT, and also compared the neovascularization at the media and adventitia of the aorta by an immunohistochemical analysis. Results: As previously reported, obvious inflammation was detected two weeks after the injection of CAWS, and also intimal thickening was observed three weeks after the injection. We found that the vasa vasorum in the adventitia of the aorta was increased in the model mice. The vasa vasorum started increasing one week after the injection of CAWS, before any obvious vasculitis was microscopically detected. Conclusion: The present results indicate that the vasculitis in Kawasaki disease starts as a disorder of the vasa vasorum.", "classifications": [ { "id": "Tanaka", "label": "Group Tanaka", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Akiko", "last_name": "Hamaoka-Okamoto", "name": null }, { "creator_type": "author", "first_name": "Chinatsu", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Tomoyo", "last_name": "Yahata", "name": null }, { "creator_type": "author", "first_name": "Kazuyuki", "last_name": "Ikeda", "name": null }, { "creator_type": "author", "first_name": "Noriko", "last_name": "Nagi-Miura", "name": null }, { "creator_type": "author", "first_name": "Naohito", "last_name": "Ohno", "name": null }, { "creator_type": "author", "first_name": "Yoshinori", "last_name": "Arai", "name": null }, { "creator_type": "author", "first_name": "Hideo", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Tetsuro", "last_name": "Takamatsu", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Hamaoka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1186/1546-0096-12-12" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "24678599" } }, "mesh": [ { "descriptor": "Adventitia", "descriptor_ui": "D063194", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Aorta", "descriptor_ui": "D001011", "major_topic": false }, { "descriptor": "Coronary Vessels", "descriptor_ui": "D003331", "major_topic": false }, { "descriptor": "Disease Models, Animal", "descriptor_ui": "D004195", "major_topic": false }, { "descriptor": "Immunohistochemistry", "descriptor_ui": "D007150", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mucocutaneous Lymph Node Syndrome", "descriptor_ui": "D009080", "major_topic": true }, { "descriptor": "Neovascularization, Pathologic", "descriptor_ui": "D009389", "major_topic": false }, { "descriptor": "Tunica Media", "descriptor_ui": "D017540", "major_topic": false }, { "descriptor": "Vasa Vasorum", "descriptor_ui": "D014651", "major_topic": true }, { "descriptor": "Vasculitis", "descriptor_ui": "D014657", "major_topic": true }, { "descriptor": "X-Ray Microtomography", "descriptor_ui": "D055114", "major_topic": false } ], "publication": { "conference_name": null, "date": "2014", "date_precision": "year", "issue": "", "normalized_date": "2014", "pages": "12", "proceedings_title": null, "publisher": "", "title": "Pediatric Rheumatology Online Journal", "volume": "12", "year": 2014 }, "ssbd": { "database": [], "repository": [] }, "title": "The involvement of the vasa vasorum in the development of vasculitis in animal model of Kawasaki disease.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Myosin V is a vesicle transporter that unidirectionally walks along cytoskeletal actin filaments by converting the chemical energy of ATP into mechanical work. Recently, it was found that myosin V force generation is a composition of two processes: a lever-arm swing, which involves a conformational change in the myosin molecule, and a Brownian search-and-catch, which involves a diffusive \"search\" by the motor domain that is followed by an asymmetric \"catch\" in the forward actin target such that Brownian motion is rectified. Here we developed a system that combines optical tweezers with DNA nano-material to show that the Brownian search-and-catch mechanism is the energetically dominant process at near stall force, providing 13 kBT of work compared to just 3 kBT by the lever-arm swing. Our result significantly reconsiders the lever-arm swinging model, which assumes the swing dominantly produces work (>10 kBT), and sheds light on the Brownian search-and-catch as a driving process.", "classifications": [ { "id": "Iwaki", "label": "Group Iwaki", "parent": "Toyoshima", "type": "group" }, { "id": "Toyoshima", "label": "Team Toyoshima", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Keisuke", "last_name": "Fujita", "name": null }, { "creator_type": "author", "first_name": "Mitsuhiro", "last_name": "Iwaki", "name": null } ], "identifiers": { "doi": { "normalized": "10.2142/biophysics.10.69" }, "pmcid": { "normalized": "PMC4629658" }, "pmid": { "normalized": "27493501" } }, "mesh": [], "publication": { "conference_name": null, "date": "2014", "date_precision": "year", "issue": "", "normalized_date": "2014", "pages": "69-75", "proceedings_title": null, "publisher": "", "title": "Biophysics (Nagoya-shi, Japan)", "volume": "10", "year": 2014 }, "ssbd": { "database": [], "repository": [] }, "title": "Myosin V is a biological Brownian machine.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "A dendritic spine is a very small structure ( approximately 0.1 microm3) of a neuron that processes input timing information. Why are spines so small? Here, we provide functional reasons; the size of spines is optimal for information coding. Spines code input timing information by the probability of Ca2+ increases, which makes robust and sensitive information coding possible. We created a stochastic simulation model of input timing-dependent Ca2+ increases in a cerebellar Purkinje cell's spine. Spines used probability coding of Ca2+ increases rather than amplitude coding for input timing detection via stochastic facilitation by utilizing the small number of molecules in a spine volume, where information per volume appeared optimal. Probability coding of Ca2+ increases in a spine volume was more robust against input fluctuation and more sensitive to input numbers than amplitude coding of Ca2+ increases in a cell volume. Thus, stochasticity is a strategy by which neurons robustly and sensitively code information.", "classifications": [ { "id": "Kuroda", "label": "Group Kuroda", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Takuya", "last_name": "Koumura", "name": null }, { "creator_type": "author", "first_name": "Hidetoshi", "last_name": "Urakubo", "name": null }, { "creator_type": "author", "first_name": "Kaoru", "last_name": "Ohashi", "name": null }, { "creator_type": "author", "first_name": "Masashi", "last_name": "Fujii", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Kuroda", "name": null } ], "identifiers": { "doi": { "normalized": "10.1371/journal.pone.0099040" }, "pmcid": { "normalized": "PMC4059641" }, "pmid": { "normalized": "24932482" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Calcium", "descriptor_ui": "D002118", "major_topic": false }, { "descriptor": "Dendritic Spines", "descriptor_ui": "D049229", "major_topic": false }, { "descriptor": "Electrical Synapses", "descriptor_ui": "D054351", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Models, Neurological", "descriptor_ui": "D008959", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Purkinje Cells", "descriptor_ui": "D011689", "major_topic": false }, { "descriptor": "Stochastic Processes", "descriptor_ui": "D013269", "major_topic": false } ], "publication": { "conference_name": null, "date": "2014", "date_precision": "year", "issue": "6", "normalized_date": "2014", "pages": "e99040", "proceedings_title": null, "publisher": "", "title": "PloS one", "volume": "9", "year": 2014 }, "ssbd": { "database": [], "repository": [] }, "title": "Stochasticity in Ca2+ increase in spines enables robust and sensitive information coding.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Background: Genome-wide saturation mutagenesis and subsequent phenotype-driven screening has been central to a comprehensive understanding of complex biological processes in classical model organisms such as flies, nematodes, and plants. The degree of “saturation” (i.e., the fraction of possible target genes identified) has been shown to be a critical parameter in determining all relevant genes involved in a biological function, without prior knowledge of their products. In mammalian model systems, however, the relatively large scale and labor intensity of experiments have hampered the achievement of actual saturation mutagenesis, especially for recessive traits that require biallelic mutations to manifest detectable phenotypes. Results: By exploiting the recently established haploid mouse embryonic stem cells (ESCs), we present an implementation of almost complete saturation mutagenesis in a mammalian system. The haploid ESCs were mutagenized with the chemical mutagen N-ethyl-N-nitrosourea (ENU) and processed for the screening of mutants defective in various steps of the glycosylphosphatidylinositol-anchor biosynthetic pathway. The resulting 114 independent mutant clones were characterized by a functional complementation assay, and were shown to be defective in any of 20 genes among all 22 known genes essential for this well-characterized pathway. Ten mutants were further validated by whole-exome sequencing. The predominant generation of single-nucleotide substitutions by ENU resulted in a gene mutation rate proportional to the length of the coding sequence, which facilitated the experimental design of saturation mutagenesis screening with the aid of computational simulation. Conclusions: Our study enables mammalian saturation mutagenesis to become a realistic proposition. Computational simulation, combined with a pilot mutagenesis experiment, could serve as a tool for the estimation of the number of genes essential for biological processes such as drug target pathways when a positive selection of mutants is available. Electronic supplementary material: The online version of this article (doi:10.1186/1471-2164-15-1016) contains supplementary material, which is available to authorized users.", "classifications": [ { "id": "Yusa", "label": "Group Yusa", "parent": "Eiraku", "type": "group" }, { "id": "Eiraku", "label": "Team Eiraku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Masahiro", "last_name": "Tokunaga", "name": null }, { "creator_type": "author", "first_name": "Chikara", "last_name": "Kokubu", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Maeda", "name": null }, { "creator_type": "author", "first_name": "Jun", "last_name": "Sese", "name": null }, { "creator_type": "author", "first_name": "Kyoji", "last_name": "Horie", "name": null }, { "creator_type": "author", "first_name": "Nakaba", "last_name": "Sugimoto", "name": null }, { "creator_type": "author", "first_name": "Taroh", "last_name": "Kinoshita", "name": null }, { "creator_type": "author", "first_name": "Kosuke", "last_name": "Yusa", "name": null }, { "creator_type": "author", "first_name": "Junji", "last_name": "Takeda", "name": null } ], "identifiers": { "doi": { "normalized": "10.1186/1471-2164-15-1016" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "25418962" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Computer Simulation", "descriptor_ui": "D003198", "major_topic": false }, { "descriptor": "Embryonic Stem Cells", "descriptor_ui": "D053595", "major_topic": false }, { "descriptor": "Ethylnitrosourea", "descriptor_ui": "D005038", "major_topic": false }, { "descriptor": "Genome", "descriptor_ui": "D016678", "major_topic": false }, { "descriptor": "Haploidy", "descriptor_ui": "D006238", "major_topic": true }, { "descriptor": "Metabolic Networks and Pathways", "descriptor_ui": "D053858", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mutagenesis", "descriptor_ui": "D016296", "major_topic": false }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": false }, { "descriptor": "Phenotype", "descriptor_ui": "D010641", "major_topic": false } ], "publication": { "conference_name": null, "date": "2014", "date_precision": "year", "issue": "1", "normalized_date": "2014", "pages": "", "proceedings_title": null, "publisher": "", "title": "BMC Genomics", "volume": "15", "year": 2014 }, "ssbd": { "database": [], "repository": [] }, "title": "Simulation and estimation of gene number in a biological pathway using almost complete saturation mutagenesis screening of haploid mouse cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Segmentation-free direct methods are quite efficient for automated nuclei extraction from high dimensional images. A few such methods do exist but most of them do not ensure algorithmic robustness to parameter and noise variations. In this research, we propose a method based on multiscale adaptive filtering for efficient and robust detection of nuclei centroids from four dimensional (4D) fluorescence images. A temporal feedback mechanism is employed between the enhancement and the initial detection steps of a typical direct method. We estimate the minimum and maximum nuclei diameters from the previous frame and feed back them as filter lengths for multiscale enhancement of the current frame. A radial intensity-gradient function is optimized at positions of initial centroids to estimate all nuclei diameters. This procedure continues for processing subsequent images in the sequence. Above mechanism thus ensures proper enhancement by automated estimation of major parameters. This brings robustness and safeguards the system against additive noises and effects from wrong parameters. Later, the method and its single-scale variant are simplified for further reduction of parameters. The proposed method is then extended for nuclei volume segmentation. The same optimization technique is applied to final centroid positions of the enhanced image and the estimated diameters are projected onto the binary candidate regions to segment nuclei volumes.Our method is finally integrated with a simple sequential tracking approach to establish nuclear trajectories in the 4D space. Experimental evaluations with five image-sequences (each having 271 3D sequential images) corresponding to five different mouse embryos show promising performances of our methods in terms of nuclear detection, segmentation, and tracking. A detail analysis with a sub-sequence of 101 3D images from an embryo reveals that the proposed method can improve the nuclei detection accuracy by 9 over the previous methods, which used inappropriate large valued parameters. Results also confirm that the proposed method and its variants achieve high detection accuracies ( 98 mean F-measure) irrespective of the large variations of filter parameters and noise levels.", "classifications": [ { "id": "Kobayashi", "label": "Group Kobayashi", "parent": "Wakamoto", "type": "group" }, { "id": "Wakamoto", "label": "Team Wakamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Md Khayrul", "last_name": "Bashar", "name": null }, { "creator_type": "author", "first_name": "Kazuo", "last_name": "Yamagata", "name": null }, { "creator_type": "author", "first_name": "Tetsuya J.", "last_name": "Kobayashi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1371/journal.pone.0101891" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "25020042" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Nucleus", "descriptor_ui": "D002467", "major_topic": false }, { "descriptor": "Embryonic Development", "descriptor_ui": "D047108", "major_topic": false }, { "descriptor": "Image Processing, Computer-Assisted", "descriptor_ui": "D007091", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Optical Imaging", "descriptor_ui": "D061848", "major_topic": false } ], "publication": { "conference_name": null, "date": "2014", "date_precision": "year", "issue": "7", "normalized_date": "2014", "pages": "", "proceedings_title": null, "publisher": "", "title": "PLoS ONE", "volume": "9", "year": 2014 }, "ssbd": { "database": [], "repository": [] }, "title": "Improved and Robust Detection of Cell Nuclei from Four Dimensional Fluorescence Images.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The hypoxia-inducible factor (HIF) prolyl hydroxylase domain enzymes (PHDs) regulate the stability of HIF protein by post-translational hydroxylation of two conserved prolyl residues in its alpha subunit in an oxygen-dependent manner. Trans-4-prolyl hydroxylation of HIFalpha under normal oxygen (O(2)) availability enables its association with the von Hippel-Lindau (VHL) tumor suppressor pVHL E3 ligase complex, leading to the degradation of HIFalpha via the ubiquitin-proteasome pathway. Due to the obligatory requirement of molecular O(2) as a co-substrate, the activity of PHDs is inhibited under hypoxic conditions, resulting in stabilized HIFalpha, which dimerizes with HIFbeta and, together with transcriptional co-activators CBP/p300, activates the transcription of its target genes. As a key molecular regulator of adaptive response to hypoxia, HIF plays important roles in multiple cellular processes and its overexpression has been detected in various cancers. The HIF1alpha isoform in particular has a strong impact on cellular metabolism, most notably by promoting anaerobic, whilst inhibiting O(2)-dependent, metabolism of glucose. The PHD enzymes also seem to have HIF-independent functions and are subject to regulation by factors other than O(2), such as by metabolic status, oxidative stress, and abnormal levels of endogenous metabolites (oncometabolites) that have been observed in some types of cancers. In this review, we aim to summarize current understandings of the function and regulation of PHDs in cancer with an emphasis on their roles in metabolism.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Ming", "last_name": "Yang", "name": null }, { "creator_type": "author", "first_name": "Huizhong", "last_name": "Su", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Kamil R.", "last_name": "Kranc", "name": null }, { "creator_type": "author", "first_name": "Patrick J.", "last_name": "Pollard", "name": null } ], "identifiers": { "doi": { "normalized": "10.2147/hp.s47968" }, "pmcid": { "normalized": "PMC5045062" }, "pmid": { "normalized": "27774472" } }, "mesh": [], "publication": { "conference_name": null, "date": "2014", "date_precision": "year", "issue": "", "normalized_date": "2014", "pages": "127-142", "proceedings_title": null, "publisher": "", "title": "Hypoxia (Auckland, N.Z.)", "volume": "2", "year": 2014 }, "ssbd": { "database": [], "repository": [] }, "title": "Prolyl hydroxylase domain enzymes: important regulators of cancer metabolism.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Endocytic vesicle fusion is inhibited during mitosis, but the molecular pathways that mediate the inhibition remain unclear. Here we uncovered an essential role of Polo-like kinase 1 (Plk1) in this mechanism. Phosphoproteomic analysis revealed that Plk1 phosphorylates the intermediate filament protein vimentin on Ser459, which is dispensable for its filament formation but is necessary for the inhibition of endocytic vesicle fusion in mitosis. Furthermore, this mechanism is required for integrin trafficking toward the cleavage furrow during cytokinesis. Our results thus identify a novel mechanism for fusion inhibition in mitosis and implicate its role in vesicle trafficking after anaphase onset.", "classifications": [ { "id": "Toyoshima", "label": "Group Toyoshima", "parent": "Toyoshima", "type": "group" }, { "id": "Toyoshima", "label": "Team Toyoshima", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Keisuke", "last_name": "Ikawa", "name": null }, { "creator_type": "author", "first_name": "Ayaka", "last_name": "Satou", "name": null }, { "creator_type": "author", "first_name": "Mitsuko", "last_name": "Fukuhara", "name": null }, { "creator_type": "author", "first_name": "Shigeru", "last_name": "Matsumura", "name": null }, { "creator_type": "author", "first_name": "Naoyuki", "last_name": "Sugiyama", "name": null }, { "creator_type": "author", "first_name": "Hidemasa", "last_name": "Goto", "name": null }, { "creator_type": "author", "first_name": "Mitsunori", "last_name": "Fukuda", "name": null }, { "creator_type": "author", "first_name": "Masaki", "last_name": "Inagaki", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Ishihama", "name": null }, { "creator_type": "author", "first_name": "Fumiko", "last_name": "Toyoshima", "name": null } ], "identifiers": { "doi": { "normalized": "10.4161/cc.26866" }, "pmcid": { "normalized": "PMC3925722" }, "pmid": { "normalized": "24196446" } }, "mesh": [ { "descriptor": "Anaphase", "descriptor_ui": "D000705", "major_topic": false }, { "descriptor": "Cell Cycle Proteins", "descriptor_ui": "D018797", "major_topic": false }, { "descriptor": "Cytokinesis", "descriptor_ui": "D048749", "major_topic": false }, { "descriptor": "HeLa Cells", "descriptor_ui": "D006367", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mitosis", "descriptor_ui": "D008938", "major_topic": false }, { "descriptor": "Phosphorylation", "descriptor_ui": "D010766", "major_topic": false }, { "descriptor": "Polo-Like Kinase 1", "descriptor_ui": "D000097869", "major_topic": false }, { "descriptor": "Protein Serine-Threonine Kinases", "descriptor_ui": "D017346", "major_topic": false }, { "descriptor": "Proto-Oncogene Proteins", "descriptor_ui": "D011518", "major_topic": false }, { "descriptor": "Transport Vesicles", "descriptor_ui": "D022161", "major_topic": false }, { "descriptor": "Vimentin", "descriptor_ui": "D014746", "major_topic": false } ], "publication": { "conference_name": null, "date": "2014", "date_precision": "year", "issue": "1", "normalized_date": "2014", "pages": "126-137", "proceedings_title": null, "publisher": "", "title": "Cell cycle (Georgetown, Tex.)", "volume": "13", "year": 2014 }, "ssbd": { "database": [], "repository": [] }, "title": "Inhibition of endocytic vesicle fusion by Plk1-mediated phosphorylation of vimentin during mitosis.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Ezrin is a membrane-associated cytoplasmic protein that serves to link cell-membrane proteins with the actin-based cytoskeleton, and also plays a role in regulation of the functional activities of some transmembrane proteins. It is expressed in placental trophoblasts. We hypothesized that placental ezrin is involved in the supply of nutrients from mother to fetus, thereby influencing fetal growth. The aim of this study was firstly to clarify the effect of ezrin on fetal growth and secondly to determine whether knockout of ezrin is associated with decreased concentrations of serum and placental nutrients. Ezrin knockout mice (Ez(-/-)) were confirmed to exhibit fetal growth retardation. Metabolome analysis of fetal serum and placental extract of ezrin knockout mice by means of capillary electrophoresis-time-of-flight mass spectrometry revealed a markedly decreased concentration of hypotaurine, a precursor of taurine. However, placental levels of cysteine and cysteine sulfinic acid (precursors of hypotaurine) and taurine were not affected. Lack of hypotaurine in Ez(-/-) mice was confirmed by liquid chromatography with tandem mass spectrometry. Administration of hypotaurine to heterogenous dams significantly decreased the placenta-to-maternal plasma ratio of hypotaurine in wild-type fetuses but only slightly decreased it in ezrin knockout fetuses, indicating that the uptake of hypotaurine from mother to placenta is saturable and that disruption of ezrin impairs the uptake of hypotaurine by placental trophoblasts. These results indicate that ezrin is required for uptake of hypotaurine from maternal serum by placental trophoblasts, and plays an important role in fetal growth.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Tomohiro", "last_name": "Nishimura", "name": null }, { "creator_type": "author", "first_name": "Kei", "last_name": "Higuchi", "name": null }, { "creator_type": "author", "first_name": "Yoshimichi", "last_name": "Sai", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Sugita", "name": null }, { "creator_type": "author", "first_name": "Yuko", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Masatoshi", "last_name": "Tomi", "name": null }, { "creator_type": "author", "first_name": "Masami", "last_name": "Wada", "name": null }, { "creator_type": "author", "first_name": "Tomohiko", "last_name": "Wakayama", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Tamura", "name": null }, { "creator_type": "author", "first_name": "Sachiko", "last_name": "Tsukita", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Emi", "last_name": "Nakashima", "name": null } ], "identifiers": { "doi": { "normalized": "10.1371/journal.pone.0105423" }, "pmcid": { "normalized": "PMC4140781" }, "pmid": { "normalized": "25144766" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cytoskeletal Proteins", "descriptor_ui": "D003598", "major_topic": false }, { "descriptor": "Disease Models, Animal", "descriptor_ui": "D004195", "major_topic": false }, { "descriptor": "Ezrin", "descriptor_ui": "D000099149", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Fetal Growth Retardation", "descriptor_ui": "D005317", "major_topic": false }, { "descriptor": "Gene Targeting", "descriptor_ui": "D018390", "major_topic": false }, { "descriptor": "Genetic Loci", "descriptor_ui": "D056426", "major_topic": false }, { "descriptor": "Homozygote", "descriptor_ui": "D006720", "major_topic": false }, { "descriptor": "Immunohistochemistry", "descriptor_ui": "D007150", "major_topic": false }, { "descriptor": "Metabolome", "descriptor_ui": "D055442", "major_topic": false }, { "descriptor": "Metabolomics", "descriptor_ui": "D055432", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Phenotype", "descriptor_ui": "D010641", "major_topic": false }, { "descriptor": "Placenta", "descriptor_ui": "D010920", "major_topic": false }, { "descriptor": "Pregnancy", "descriptor_ui": "D011247", "major_topic": false }, { "descriptor": "Taurine", "descriptor_ui": "D013654", "major_topic": false } ], "publication": { "conference_name": null, "date": "2014", "date_precision": "year", "issue": "8", "normalized_date": "2014", "pages": "e105423", "proceedings_title": null, "publisher": "", "title": "PloS one", "volume": "9", "year": 2014 }, "ssbd": { "database": [], "repository": [] }, "title": "Fetal growth retardation and lack of hypotaurine in ezrin knockout mice.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Stochasticity ubiquitously inevitably appears at all levels from molecular traits to multicellular, morphological traits. Intrinsic stochasticity in biochemical reactions underlies the typical intercellular distributions of chemical concentrations, e.g., morphogen gradients, which can give rise to stochastic morphogenesis. While the universal statistics and mechanisms underlying the stochasticity at the biochemical level have been widely analyzed, those at the morphological level have not. Such morphological stochasticity is found in foral organ numbers. Although the floral organ number is a hallmark of floral species, it can distribute stochastically even within an individual plant. The probability distribution of the floral organ number within a population is usually asymmetric, i.e., it is more likely to increase rather than decrease from the modal value, or vice versa. We combined field observations, statistical analysis, and mathematical modeling to study the developmental basis of the variation in floral organ numbers among 50 species mainly from Ranunculaceae and several other families from core eudicots. We compared six hypothetical mechanisms and found that a modified error function reproduced much of the asymmetric variation found in eudicot floral organ numbers. The error function is derived from mathematical modeling of floral organ positioning, and its parameters represent measurable distances in the floral bud morphologies. The model predicts two developmental sources of the organ-number distributions: stochastic shifts in the expression boundaries of homeotic genes and a semi-concentric (whorled-type) organ arrangement. Other models species- or organ-specifically reproduced different types of distributions that reflect different developmental processes. The organ-number variation could be an indicator of stochasticity in organ fate determination and organ positioning.", "classifications": [ { "id": "Fujimoto", "label": "Group Fujimoto", "parent": "Ueda", "type": "group" }, { "id": "Ueda", "label": "Team Ueda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Miho S.", "last_name": "Kitazawa", "name": null }, { "creator_type": "author", "first_name": "Koichi", "last_name": "Fujimoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.3389/fpls.2014.00545" }, "pmcid": { "normalized": "PMC4217355" }, "pmid": { "normalized": "25404932" } }, "mesh": [], "publication": { "conference_name": null, "date": "2014", "date_precision": "year", "issue": "", "normalized_date": "2014", "pages": "545", "proceedings_title": null, "publisher": "", "title": "Frontiers in plant science", "volume": "5", "year": 2014 }, "ssbd": { "database": [], "repository": [] }, "title": "A developmental basis for stochasticity in floral organ numbers.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Some animal influenza A viruses (IAVs) bind not only to N-acetylneuraminic acid (Neu5Ac) but also to N-glycolylneuraminic acid (Neu5Gc), which has been discussed as a virus receptor. Human cells cannot synthesize Neu5Gc due to dysfunction of the CMP-Neu5Ac hydroxylase (CMAH) gene, which converts CMP-Neu5Ac to CMP-Neu5Gc. However, exogenous Neu5Gc from Neu5Gc-rich dietary sources is able to be metabolically incorporated into surfaces of tissue cells and may be related to enhancement of the infectivity and severity of IAV. Here, we investigated the receptor function of Neu5Gc on IAV infection in Neu5Gc-expressing cells by transfection of the monkey CMAH gene into human cells or by incubation with human cells in the presence of N-glycolylmannosamine. Expression of Neu5Gc on human cells clearly suppressed infectivity of IAVs that possess Neu5Gc binding ability. Furthermore, there was no difference in infectivity of a transfectant virus that included the wild-type HA gene from A/Memphis/1/1971 (H3N2), which shows no Neu5Gc binding, between parent MCF7 cells and cells stably expressing the monkey CMAH gene (CMAH-MCF7 cells). On the other hand, cell entry of the transfectant virus that included the Neu5Gc-binding HA gene with a single mutation to Tyr at position Thr155 was arrested at the stage of internalization from the plasma membrane of the CMAH-MCF7 cells. These results indicate that expression of Neu5Gc on the surface of human epithelial cells suppresses infection of IAVs that possess Neu5Gc binding ability. Neu5Gc is suggested to work as a decoy receptor of Neu5Gc-binding IAVs but not a functional receptor for IAV infection. IMPORTANCE: Influenza A viruses (IAVs) bind to the host cell surfaces through sialic acids at the terminal of glycoconjugates. For IAV binding to sialic acids, some IAVs bind not only to N-acetylneuraminic acid (Neu5Ac) as a receptor but also to N-glycolylneuraminic acid (Neu5Gc). Neu5Gc has been discussed as a receptor of human and animal IAVs. Our results showed that Neu5Gc expression on human epithelial cells suppresses infection of IAVs that possess Neu5Gc binding ability. Neu5Gc is suggested to be a \"decoy receptor\" of Neu5Gc-binding IAVs but not a functional receptor for IAV infection. Human cells cannot synthesize Neu5Gc because of dysfunction of the CMP-N-acetylneuraminic acid hydroxylase gene but can exogenously and metabolically incorporate Neu5Gc from dietary sources. The expression of Neu5Gc on human epithelial cells by taking in exogenous Neu5Gc from Neu5Gc-rich dietary sources may be related to restriction of the infection of IAVs that have acquired Neu5Gc binding ability.", "classifications": [ { "id": "Suzuki", "label": "Group Suzuki", "parent": "Takekawa", "type": "group" }, { "id": "Takekawa", "label": "Team Takekawa", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Tadanobu", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Maiko", "last_name": "Takano", "name": null }, { "creator_type": "author", "first_name": "Yuuki", "last_name": "Kurebayashi", "name": null }, { "creator_type": "author", "first_name": "Midori", "last_name": "Masuda", "name": null }, { "creator_type": "author", "first_name": "Sawako", "last_name": "Kawagishi", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Takaguchi", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Yamanaka", "name": null }, { "creator_type": "author", "first_name": "Akira", "last_name": "Minami", "name": null }, { "creator_type": "author", "first_name": "Tadamune", "last_name": "Otsubo", "name": null }, { "creator_type": "author", "first_name": "Kiyoshi", "last_name": "Ikeda", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Suzuki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1128/jvi.00716-14" }, "pmcid": { "normalized": "PMC4135951" }, "pmid": { "normalized": "24829344" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "Cell Membrane", "descriptor_ui": "D002462", "major_topic": false }, { "descriptor": "Epithelial Cells", "descriptor_ui": "D004847", "major_topic": false }, { "descriptor": "Haplorhini", "descriptor_ui": "D000882", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Influenza A virus", "descriptor_ui": "D009980", "major_topic": false }, { "descriptor": "Neuraminic Acids", "descriptor_ui": "D009438", "major_topic": false }, { "descriptor": "Receptors, Virus", "descriptor_ui": "D011991", "major_topic": false }, { "descriptor": "Virus Internalization", "descriptor_ui": "D053586", "major_topic": true } ], "publication": { "conference_name": null, "date": "2014 Aug", "date_precision": "unknown", "issue": "15", "normalized_date": null, "pages": "8445-8456", "proceedings_title": null, "publisher": "", "title": "Journal of virology", "volume": "88", "year": 2014 }, "ssbd": { "database": [], "repository": [] }, "title": "N-glycolylneuraminic acid on human epithelial cells prevents entry of influenza A viruses that possess N-glycolylneuraminic acid binding ability.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The mammalian brain consists of a complex ensemble of neurons and glia. Their production during development and remodeling is tightly controlled by various regulatory mechanisms in neural progenitor cells (NPCs). Among such regulations, basic helix-loop-helix (bHLH) factors have key functions in the self-renewal, multipotency, and fate determination of NPCs. Here, we highlight the importance of the expression dynamics of bHLH factors in these processes. The oscillatory expression of multiple bHLH factors is correlated with the multipotent and self-renewable state, whereas sustained expression of a selected bHLH factor regulates fate determination. We also discuss potential mechanisms by which a single bHLH factor can exhibit versatile functions in NPC regulation as well as the hierarchical structure of the bHLH factor oscillatory network.", "classifications": [ { "id": "Imayoshi", "label": "Group Imayoshi", "parent": "Imayoshi", "type": "group" }, { "id": "Imayoshi", "label": "Team Imayoshi", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Itaru", "last_name": "Imayoshi", "name": null }, { "creator_type": "author", "first_name": "Ryoichiro", "last_name": "Kageyama", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.tins.2014.07.006" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "25149265" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Basic Helix-Loop-Helix Proteins", "descriptor_ui": "D051792", "major_topic": false }, { "descriptor": "Gene Expression Regulation", "descriptor_ui": "D005786", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Neural Stem Cells", "descriptor_ui": "D058953", "major_topic": false } ], "publication": { "conference_name": null, "date": "2014 Oct", "date_precision": "unknown", "issue": "10", "normalized_date": null, "pages": "531-538", "proceedings_title": null, "publisher": "", "title": "Trends in neurosciences", "volume": "37", "year": 2014 }, "ssbd": { "database": [], "repository": [] }, "title": "Oscillatory control of bHLH factors in neural progenitors.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Helicobacter cinaedi was first isolated from rectal cultures from homosexual men in 1984. In the 1980s to mid 1990s, the microorganism was mainly isolated from samples from homosexual men or immunocompromised patients; however, during the last two decades, H. cinaedi has been isolated from immunocompromised and from immunocompetent individuals worldwide. In Japan, the isolation of this microorganism was first reported in 2003. Since then, many cases have been reported in hospitals across the country. Despite many reports, the etiological properties and pathogenicity of H. cinaedi remain elusive; however, we are increasingly able to recognize some of the features and the clinical relevance of infection. In particular, a long incubation period is essential for detection in an automatic blood culture system and many of the recent isolates are resistant to both macrolides and quinolones. Furthermore, there is an association between infection and severe or chronic illnesses, such as meningitis or arteriosclerosis, in addition to mild diseases such as fever, abdominal pain, gastroenteritis, proctitis, diarrhea, erysipelas, cellulitis, arthritis, and bacteremia. In this review, we introduce the current knowledge and our latest findings relating to H. cinaedi.", "classifications": [ { "id": "Akaike", "label": "Group Akaike", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yoshiaki", "last_name": "Kawamura", "name": null }, { "creator_type": "author", "first_name": "Junko", "last_name": "Tomida", "name": null }, { "creator_type": "author", "first_name": "Yuji", "last_name": "Morita", "name": null }, { "creator_type": "author", "first_name": "Shigemoto", "last_name": "Fujii", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Okamoto", "name": null }, { "creator_type": "author", "first_name": "Takaaki", "last_name": "Akaike", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.jiac.2014.06.007" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "25022901" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Communicable Diseases", "descriptor_ui": "D003141", "major_topic": false }, { "descriptor": "Helicobacter", "descriptor_ui": "D016998", "major_topic": false }, { "descriptor": "Helicobacter Infections", "descriptor_ui": "D016481", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false } ], "publication": { "conference_name": null, "date": "2014 Sep", "date_precision": "unknown", "issue": "9", "normalized_date": null, "pages": "517-526", "proceedings_title": null, "publisher": "", "title": "Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy", "volume": "20", "year": 2014 }, "ssbd": { "database": [], "repository": [] }, "title": "Clinical and bacteriological characteristics of Helicobacter cinaedi infection.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: ATP-binding cassette (ABC) transporters play various roles in cancer biology and drug resistance, but their association with outcomes in serous epithelial ovarian cancer (EOC) is unknown. METHODS: The relationship between clinical outcomes and ABC transporter gene expression in two independent cohorts of high-grade serous EOC tumors was assessed with real-time quantitative polymerase chain reaction, analysis of expression microarray data, and immunohistochemistry. Associations between clinical outcomes and ABCA transporter gene single nucleotide polymorphisms were tested in a genome-wide association study. Impact of short interfering RNA-mediated gene suppression was determined by colony forming and migration assays. Association with survival was assessed with Kaplan-Meier analysis and log-rank tests. All statistical tests were two-sided. RESULTS: Associations with outcome were observed with ABC transporters of the \"A\" subfamily, but not with multidrug transporters. High-level expression of ABCA1, ABCA6, ABCA8, and ABCA9 in primary tumors was statistically significantly associated with reduced survival in serous ovarian cancer patients. Low levels of ABCA5 and the C-allele of rs536009 were associated with shorter overall survival (hazard ratio for death = 1.50; 95% confidence interval [CI] =1.26 to 1.79; P = 6.5e-6). The combined expression pattern of ABCA1, ABCA5, and either ABCA8 or ABCA9 was associated with particularly poor outcome (mean overall survival in group with adverse ABCA1, ABCA5 and ABCA9 gene expression = 33.2 months, 95% CI = 26.4 to 40.1; vs 55.3 months in the group with favorable ABCA gene expression, 95% CI = 49.8 to 60.8; P = .001), independently of tumor stage or surgical debulking status. Suppression of cholesterol transporter ABCA1 inhibited ovarian cancer cell growth and migration in vitro, and statin treatment reduced ovarian cancer cell migration. CONCLUSIONS: Expression of ABCA transporters was associated with poor outcome in serous ovarian cancer, implicating lipid trafficking as a potentially important process in EOC.", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Ellen L.", "last_name": "Hedditch", "name": null }, { "creator_type": "author", "first_name": "Bo", "last_name": "Gao", "name": null }, { "creator_type": "author", "first_name": "Amanda J.", "last_name": "Russell", "name": null }, { "creator_type": "author", "first_name": "Yi", "last_name": "Lu", "name": null }, { "creator_type": "author", "first_name": "Catherine", "last_name": "Emmanuel", "name": null }, { "creator_type": "author", "first_name": "Jonathan", "last_name": "Beesley", "name": null }, { "creator_type": "author", "first_name": "Sharon E.", "last_name": "Johnatty", "name": null }, { "creator_type": "author", "first_name": "Xiaoqing", "last_name": "Chen", "name": null }, { "creator_type": "author", "first_name": "Paul", "last_name": "Harnett", "name": null }, { "creator_type": "author", "first_name": "Joshy", "last_name": "George", "name": null }, { "creator_type": "author", "first_name": "Rebekka T.", "last_name": "Williams", "name": null }, { "creator_type": "author", "first_name": "Claudia", "last_name": "Flemming", "name": null }, { "creator_type": "author", "first_name": "Diether", "last_name": "Lambrechts", "name": null }, { "creator_type": "author", "first_name": "Evelyn", "last_name": "Despierre", "name": null }, { "creator_type": "author", "first_name": "Sandrina", "last_name": "Lambrechts", "name": null }, { "creator_type": "author", "first_name": "Ignace", "last_name": "Vergote", "name": null }, { "creator_type": "author", "first_name": "Beth", "last_name": "Karlan", "name": null }, { "creator_type": "author", "first_name": "Jenny", "last_name": "Lester", "name": null }, { "creator_type": "author", "first_name": "Sandra", "last_name": "Orsulic", "name": null }, { "creator_type": "author", "first_name": "Christine", "last_name": "Walsh", "name": null }, { "creator_type": "author", "first_name": "Peter", "last_name": "Fasching", "name": null }, { "creator_type": "author", "first_name": "Matthias W.", "last_name": "Beckmann", "name": null }, { "creator_type": "author", "first_name": "Arif B.", "last_name": "Ekici", "name": null }, { "creator_type": "author", "first_name": "Alexander", "last_name": "Hein", "name": null }, { "creator_type": "author", "first_name": "Keitaro", "last_name": "Matsuo", "name": null }, { "creator_type": "author", "first_name": "Satoyo", "last_name": "Hosono", "name": null }, { "creator_type": "author", "first_name": "Toru", "last_name": "Nakanishi", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null }, { "creator_type": "author", "first_name": "Tanja", "last_name": "Pejovic", "name": null }, { "creator_type": "author", "first_name": "Yukie", "last_name": "Bean", "name": null }, { "creator_type": "author", "first_name": "Florian", "last_name": "Heitz", "name": null }, { "creator_type": "author", "first_name": "Philipp", "last_name": "Harter", "name": null }, { "creator_type": "author", "first_name": "Andreas", "last_name": "du Bois", "name": null }, { "creator_type": "author", "first_name": "Ira", "last_name": "Schwaab", "name": null }, { "creator_type": "author", "first_name": "Estrid", "last_name": "Hogdall", "name": null }, { "creator_type": "author", "first_name": "Susan K.", "last_name": "Kjaer", "name": null }, { "creator_type": "author", "first_name": "Allan", "last_name": "Jensen", "name": null }, { "creator_type": "author", "first_name": "Claus", "last_name": "Hogdall", "name": null }, { "creator_type": "author", "first_name": "Lene", "last_name": "Lundvall", "name": null }, { "creator_type": "author", "first_name": "Svend Aage", "last_name": "Engelholm", "name": null }, { "creator_type": "author", "first_name": "Bob", "last_name": "Brown", "name": null }, { "creator_type": "author", "first_name": "James", "last_name": "Flanagan", "name": null }, { "creator_type": "author", "first_name": "Michelle D.", "last_name": "Metcalf", "name": null }, { "creator_type": "author", "first_name": "Nadeem", "last_name": "Siddiqui", "name": null }, { "creator_type": "author", "first_name": "Thomas", "last_name": "Sellers", "name": null }, { "creator_type": "author", "first_name": "Brooke", "last_name": "Fridley", "name": null }, { "creator_type": "author", "first_name": "Julie", "last_name": "Cunningham", "name": null }, { "creator_type": "author", "first_name": "Joellen", "last_name": "Schildkraut", "name": null }, { "creator_type": "author", "first_name": "Ed", "last_name": "Iversen", "name": null }, { "creator_type": "author", "first_name": "Rachel P.", "last_name": "Weber", "name": null }, { "creator_type": "author", "first_name": "Andrew", "last_name": "Berchuck", "name": null }, { "creator_type": "author", "first_name": "Ellen", "last_name": "Goode", "name": null }, { "creator_type": "author", "first_name": "David D.", "last_name": "Bowtell", "name": null }, { "creator_type": "author", "first_name": "Georgia", "last_name": "Chenevix-Trench", "name": null }, { "creator_type": "author", "first_name": "Anna", "last_name": "deFazio", "name": null }, { "creator_type": "author", "first_name": "Murray D.", "last_name": "Norris", "name": null }, { "creator_type": "author", "first_name": "Stuart", "last_name": "MacGregor", "name": null }, { "creator_type": "author", "first_name": "Michelle", "last_name": "Haber", "name": null }, { "creator_type": "author", "first_name": "Michelle J.", "last_name": "Henderson", "name": null } ], "identifiers": { "doi": { "normalized": "10.1093/jnci/dju149" }, "pmcid": { "normalized": "PMC4110473" }, "pmid": { "normalized": "24957074" } }, "mesh": [ { "descriptor": "ATP Binding Cassette Transporter 1", "descriptor_ui": "D064286", "major_topic": false }, { "descriptor": "ATP-Binding Cassette Transporters", "descriptor_ui": "D018528", "major_topic": false }, { "descriptor": "Carcinoma, Ovarian Epithelial", "descriptor_ui": "D000077216", "major_topic": false }, { "descriptor": "Cell Movement", "descriptor_ui": "D002465", "major_topic": false }, { "descriptor": "Cystadenocarcinoma, Serous", "descriptor_ui": "D018284", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Gene Expression Regulation, Neoplastic", "descriptor_ui": "D015972", "major_topic": false }, { "descriptor": "Genome-Wide Association Study", "descriptor_ui": "D055106", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Kaplan-Meier Estimate", "descriptor_ui": "D053208", "major_topic": false }, { "descriptor": "Neoplasm Grading", "descriptor_ui": "D060787", "major_topic": false }, { "descriptor": "Neoplasms, Glandular and Epithelial", "descriptor_ui": "D009375", "major_topic": false }, { "descriptor": "Neoplastic Stem Cells", "descriptor_ui": "D014411", "major_topic": false }, { "descriptor": "Ovarian Neoplasms", "descriptor_ui": "D010051", "major_topic": false }, { "descriptor": "Polymorphism, Single Nucleotide", "descriptor_ui": "D020641", "major_topic": true }, { "descriptor": "Real-Time Polymerase Chain Reaction", "descriptor_ui": "D060888", "major_topic": false }, { "descriptor": "RNA, Messenger", "descriptor_ui": "D012333", "major_topic": false } ], "publication": { "conference_name": null, "date": "2014 Jul", "date_precision": "unknown", "issue": "7", "normalized_date": null, "pages": "dju149", "proceedings_title": null, "publisher": "", "title": "Journal of the National Cancer Institute", "volume": "106", "year": 2014 }, "ssbd": { "database": [], "repository": [] }, "title": "ABCA transporter gene expression and poor outcome in epithelial ovarian cancer.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Few articles have been published on the imaging findings of anaplastic lymphoma kinase (ALK)-positive non-small-cell lung cancer (NSCLC). To investigate the radiological findings of ALK-positive NSCLC in the advanced stage, CT scans were examined. In addition, the response to chemotherapy was evaluated. Of the 36 patients with ALK-rearranged NSCLC, a mass and a nodule were identified in 17 (47.2%) and 16 (44.4%), respectively, indicating that more than 40% had a small-sized tumor. Overall, 31 (86.1%) patients had lymphadenopathy, seven (19.4%) had extranodal lymph node invasion, and three (8.3%) had lymphangitis. A pleural effusion was seen in 15 patients (41.7%). All but one patient had no ground-glass opacity (GGO) lesions, indicating that most ALK-positive tumors showed a solid growth pattern without GGO on CT. Twenty were evaluable for response to chemotherapy; 10 (50.0%) had a partial response (PR), nine (45.0%) had stable disease (SD), and one (5.0%) had progressive disease (PD) with first-line chemotherapy. With second-line chemotherapy, five (26.3%) had PR, 11 (57.9%) had SD, and three (15.8%) had PD. The five patients with PR were all treated by using crizotinib. Time to progression was 8.2 months with first-line chemotherapy, and 6.0 months with second-line chemotherapy. Advanced-stage ALK-positive tumors have a relatively aggressive phenotype, which cannot be inferred from the size of the tumor alone. ALK-positive patients have a good response to first-line cytotoxic drugs and to crizotinib as second-line therapy, but a relatively poor response to cytotoxic drugs as second-line therapy.", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Jangchul", "last_name": "Park", "name": null }, { "creator_type": "author", "first_name": "Hidekazu", "last_name": "Yamaura", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null }, { "creator_type": "author", "first_name": "Waki", "last_name": "Hosoda", "name": null }, { "creator_type": "author", "first_name": "Chiaki", "last_name": "Kondo", "name": null }, { "creator_type": "author", "first_name": "Junichi", "last_name": "Shimizu", "name": null }, { "creator_type": "author", "first_name": "Yoshitsugu", "last_name": "Horio", "name": null }, { "creator_type": "author", "first_name": "Kimihide", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Kosuke", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Tomoyo", "last_name": "Oguri", "name": null }, { "creator_type": "author", "first_name": "Yoshihisa", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Toyoaki", "last_name": "Hida", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/cam4.172" }, "pmcid": { "normalized": "PMC3930396" }, "pmid": { "normalized": "24403104" } }, "mesh": [ { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Anaplastic Lymphoma Kinase", "descriptor_ui": "D000077548", "major_topic": false }, { "descriptor": "Antineoplastic Agents", "descriptor_ui": "D000970", "major_topic": false }, { "descriptor": "Carcinoma, Non-Small-Cell Lung", "descriptor_ui": "D002289", "major_topic": false }, { "descriptor": "Crizotinib", "descriptor_ui": "D000077547", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Gene Rearrangement", "descriptor_ui": "D015321", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Lymph Nodes", "descriptor_ui": "D008198", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Neoplasm Staging", "descriptor_ui": "D009367", "major_topic": false }, { "descriptor": "Oncogene Proteins, Fusion", "descriptor_ui": "D015514", "major_topic": false }, { "descriptor": "Protein Kinase Inhibitors", "descriptor_ui": "D047428", "major_topic": false }, { "descriptor": "Pyrazoles", "descriptor_ui": "D011720", "major_topic": false }, { "descriptor": "Pyridines", "descriptor_ui": "D011725", "major_topic": false }, { "descriptor": "Receptor Protein-Tyrosine Kinases", "descriptor_ui": "D020794", "major_topic": false }, { "descriptor": "Tomography, X-Ray Computed", "descriptor_ui": "D014057", "major_topic": false } ], "publication": { "conference_name": null, "date": "2014 Feb", "date_precision": "unknown", "issue": "1", "normalized_date": null, "pages": "118-123", "proceedings_title": null, "publisher": "", "title": "Cancer medicine", "volume": "3", "year": 2014 }, "ssbd": { "database": [], "repository": [] }, "title": "Anaplastic lymphoma kinase gene rearrangements in patients with advanced-stage non-small-cell lung cancer: CT characteristics and response to chemotherapy.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The prognosis of advanced colon cancer patients is profoundly affected by the presence or absence of liver metastasis. miR-493 functions as a potent suppressor of liver metastasis, and low-level miR-493 expression in human primary colon cancer is associated with an elevated incidence of liver metastasis. We previously showed that IGF1R is a target gene of miR-493, and that the inhibition of IGF1R partly explains how miR-493 suppresses liver metastasis. However, major functional targets that mediate the antimetastatic activity of miR-493 remain elusive. Here, we extended our search for target genes and identified MKK7, a mitogen-activated protein kinase kinase, as a novel target of miR-493. miR-493 inhibits MKK7 expression by targeting the binding site at the 3′-UTR of the mkk7 gene. MKK7 was expressed in six out of seven colon cancer cell lines examined but not in non-transformed colon epithelial cells, and its expression was required for the activating phosphorylation of JNK. RNA interference-mediated inhibition of MKK7 resulted in marked suppression of liver metastasis of colon cancer cells. A significant decrease of metastasized cells by the MKK7 knockdown was observed, even at early stages of the metastatic settlement, in accordance with a time course of the miR-493-mediated inhibition of the metastasis. Immunohistochemical examination in human primary colon tumors revealed that the occurrence of liver metastasis is associated with elevated levels of MKK7. Thus, MKK7 is a major functional target of miR-493, and its suppression thwarts liver metastasis of colon cancer cells.", "classifications": [ { "id": "Okamoto", "label": "Group Okamoto", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Hiroaki", "last_name": "Sakai", "name": null }, { "creator_type": "author", "first_name": "Ai", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Aihara", "name": null }, { "creator_type": "author", "first_name": "Yoshinori", "last_name": "Ikarashi", "name": null }, { "creator_type": "author", "first_name": "Yutaka", "last_name": "Midorikawa", "name": null }, { "creator_type": "author", "first_name": "Michael", "last_name": "Kracht", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Nakagama", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Okamoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/cas.12380" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "24533778" } }, "mesh": [ { "descriptor": "3' Untranslated Regions", "descriptor_ui": "D020413", "major_topic": false }, { "descriptor": "Binding Sites", "descriptor_ui": "D001665", "major_topic": false }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Colonic Neoplasms", "descriptor_ui": "D003110", "major_topic": false }, { "descriptor": "Gene Expression Regulation, Neoplastic", "descriptor_ui": "D015972", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Liver Neoplasms", "descriptor_ui": "D008113", "major_topic": false }, { "descriptor": "MAP Kinase Kinase 7", "descriptor_ui": "D048688", "major_topic": false }, { "descriptor": "MicroRNAs", "descriptor_ui": "D035683", "major_topic": false }, { "descriptor": "Receptor, IGF Type 1", "descriptor_ui": "D017526", "major_topic": false } ], "publication": { "conference_name": null, "date": "2014 Apr", "date_precision": "unknown", "issue": "4", "normalized_date": null, "pages": "425-430", "proceedings_title": null, "publisher": "", "title": "Cancer Science", "volume": "105", "year": 2014 }, "ssbd": { "database": [], "repository": [] }, "title": "MKK7 mediates miR-493-dependent suppression of liver metastasis of colon cancer cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Tissue damage by oxidative stress is a key pathogenic mechanism in various diseases, including AKI and CKD. Thus, early detection of oxidative tissue damage is important. Using a tRNA-specific modified nucleoside 1-methyladenosine (m1A) antibody, we show that oxidative stress induces a direct conformational change in tRNA structure that promotes subsequent tRNA fragmentation and occurs much earlier than DNA damage. In various models of tissue damage (ischemic reperfusion, toxic injury, and irradiation), the levels of circulating tRNA derivatives increased rapidly. In humans, the levels of circulating tRNA derivatives also increased under conditions of acute renal ischemia, even before levels of other known tissue damage markers increased. Notably, the level of circulating free m1A correlated with mortality in the general population (n=1033) over a mean follow-up of 6.7 years. Compared with healthy controls, patients with CKD had higher levels of circulating free m1A, which were reduced by treatment with pitavastatin (2 mg/d; n=29). Therefore, tRNA damage reflects early oxidative stress damage, and detection of tRNA damage may be a useful tool for identifying organ damage and forming a clinical prognosis.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Eikan", "last_name": "Mishima", "name": null }, { "creator_type": "author", "first_name": "Chisako", "last_name": "Inoue", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Saigusa", "name": null }, { "creator_type": "author", "first_name": "Ryusuke", "last_name": "Inoue", "name": null }, { "creator_type": "author", "first_name": "Koki", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Jinno", "name": null }, { "creator_type": "author", "first_name": "Yuri", "last_name": "Tsukui", "name": null }, { "creator_type": "author", "first_name": "Yosuke", "last_name": "Akamatsu", "name": null }, { "creator_type": "author", "first_name": "Masatake", "last_name": "Araki", "name": null }, { "creator_type": "author", "first_name": "Kimi", "last_name": "Araki", "name": null }, { "creator_type": "author", "first_name": "Ritsuko", "last_name": "Shimizu", "name": null }, { "creator_type": "author", "first_name": "Haruka", "last_name": "Shinke", "name": null }, { "creator_type": "author", "first_name": "Takehiro", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Yoichi", "last_name": "Takeuchi", "name": null }, { "creator_type": "author", "first_name": "Hisato", "last_name": "Shima", "name": null }, { "creator_type": "author", "first_name": "Yasutoshi", "last_name": "Akiyama", "name": null }, { "creator_type": "author", "first_name": "Takafumi", "last_name": "Toyohara", "name": null }, { "creator_type": "author", "first_name": "Chitose", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Yoshikatu", "last_name": "Saiki", "name": null }, { "creator_type": "author", "first_name": "Teiji", "last_name": "Tominaga", "name": null }, { "creator_type": "author", "first_name": "Shigehito", "last_name": "Miyagi", "name": null }, { "creator_type": "author", "first_name": "Naoki", "last_name": "Kawagisihi", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Takayoshi", "last_name": "Ohkubo", "name": null }, { "creator_type": "author", "first_name": "Kenichi", "last_name": "Yamamura", "name": null }, { "creator_type": "author", "first_name": "Yutaka", "last_name": "Imai", "name": null }, { "creator_type": "author", "first_name": "Satohiro", "last_name": "Masuda", "name": null }, { "creator_type": "author", "first_name": "Venkata", "last_name": "Sabbisetti", "name": null }, { "creator_type": "author", "first_name": "Takaharu", "last_name": "Ichimura", "name": null }, { "creator_type": "author", "first_name": "David B.", "last_name": "Mount", "name": null }, { "creator_type": "author", "first_name": "Joseph V.", "last_name": "Bonventre", "name": null }, { "creator_type": "author", "first_name": "Sadayoshi", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Yoshihisa", "last_name": "Tomioka", "name": null }, { "creator_type": "author", "first_name": "Kunihiko", "last_name": "Itoh", "name": null }, { "creator_type": "author", "first_name": "Takaaki", "last_name": "Abe", "name": null } ], "identifiers": { "doi": { "normalized": "10.1681/asn.2013091001" }, "pmcid": { "normalized": "PMC4178440" }, "pmid": { "normalized": "24833129" } }, "mesh": [ { "descriptor": "Acute Kidney Injury", "descriptor_ui": "D058186", "major_topic": false }, { "descriptor": "Adenosine", "descriptor_ui": "D000241", "major_topic": false }, { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Apoptosis", "descriptor_ui": "D017209", "major_topic": false }, { "descriptor": "Case-Control Studies", "descriptor_ui": "D016022", "major_topic": false }, { "descriptor": "DNA Damage", "descriptor_ui": "D004249", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Japan", "descriptor_ui": "D007564", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Molecular Conformation", "descriptor_ui": "D008968", "major_topic": false }, { "descriptor": "Oxidative Stress", "descriptor_ui": "D018384", "major_topic": true }, { "descriptor": "Rats, Wistar", "descriptor_ui": "D017208", "major_topic": false }, { "descriptor": "Renal Insufficiency, Chronic", "descriptor_ui": "D051436", "major_topic": false }, { "descriptor": "RNA, Transfer", "descriptor_ui": "D012343", "major_topic": false } ], "publication": { "conference_name": null, "date": "2014 Oct", "date_precision": "unknown", "issue": "10", "normalized_date": null, "pages": "2316-2326", "proceedings_title": null, "publisher": "", "title": "Journal of the American Society of Nephrology : JASN", "volume": "25", "year": 2014 }, "ssbd": { "database": [], "repository": [] }, "title": "Conformational change in transfer RNA is an early indicator of acute cellular damage.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Mammalian cardiomyocytes withdraw from the cell cycle shortly after birth, although it remains unclear how cardiomyocyte cell cycles behave during development. Compared to conventional immunohistochemistry in static observation, time-lapse imaging can reveal comprehensive data in hard-to-understand biological phenomenon. However, there are no reports of an established protocol of successful time-lapse imaging in mammalian heart. Thus, it is valuable to establish a time-lapse imaging system to enable the observation of cell cycle dynamics in living murine cardiomyocytes. This study sought to establish time-lapse imaging of murine heart to study cardiomyocyte cell cycle behavior. The Fucci (fluorescent ubiquitination-based cell cycle indicator) system can effectively label individual G1, S/G2/M, and G1/S-transition phase nuclei red, green and yellow, respectively, in living mammalian cells, and could therefore be useful to visualize the real-time cell cycle transitions in living murine heart. To establish a similar system for time-lapse imaging of murine heart, we first developed an ex vivo culture system, with the culture conditions determined in terms of sample state, serum concentration, and oxygen concentration. The optimal condition (slice culture, oxygen concentration 20%, serum concentration 10%) successfully mimicked physiological cardiomyocyte proliferation in vivo. Time-lapse imaging of cardiac slices from E11.5, E14.5, E18.5, and P1 Fucci-expressing transgenic mice revealed an elongated S/G2/M phase in cardiomyocytes during development. Our time-lapse imaging of murine heart revealed a gradual elongation of the S/G2/M phase during development in living cardiomyocytes.", "classifications": [ { "id": "Sawano", "label": "Group Sawano", "parent": "Shintaku", "type": "group" }, { "id": "Shintaku", "label": "Team Shintaku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Hisayuki", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Shinsuke", "last_name": "Yuasa", "name": null }, { "creator_type": "author", "first_name": "Hidenori", "last_name": "Tabata", "name": null }, { "creator_type": "author", "first_name": "Shugo", "last_name": "Tohyama", "name": null }, { "creator_type": "author", "first_name": "Nozomi", "last_name": "Hayashiji", "name": null }, { "creator_type": "author", "first_name": "Fumiyuki", "last_name": "Hattori", "name": null }, { "creator_type": "author", "first_name": "Naoto", "last_name": "Muraoka", "name": null }, { "creator_type": "author", "first_name": "Toru", "last_name": "Egashira", "name": null }, { "creator_type": "author", "first_name": "Shinichiro", "last_name": "Okata", "name": null }, { "creator_type": "author", "first_name": "Kojiro", "last_name": "Yae", "name": null }, { "creator_type": "author", "first_name": "Tomohisa", "last_name": "Seki", "name": null }, { "creator_type": "author", "first_name": "Takahiko", "last_name": "Nishiyama", "name": null }, { "creator_type": "author", "first_name": "Kazunori", "last_name": "Nakajima", "name": null }, { "creator_type": "author", "first_name": "Asako", "last_name": "Sakaue-Sawano", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Miyawaki", "name": null }, { "creator_type": "author", "first_name": "Keiichi", "last_name": "Fukuda", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.yjmcc.2014.03.020" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "24704900" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Cycle", "descriptor_ui": "D002453", "major_topic": false }, { "descriptor": "Cell Proliferation", "descriptor_ui": "D049109", "major_topic": false }, { "descriptor": "Embryo, Mammalian", "descriptor_ui": "D004622", "major_topic": false }, { "descriptor": "Embryonic Development", "descriptor_ui": "D047108", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Fluorescent Dyes", "descriptor_ui": "D005456", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Transgenic", "descriptor_ui": "D008822", "major_topic": false }, { "descriptor": "Microscopy, Fluorescence", "descriptor_ui": "D008856", "major_topic": false }, { "descriptor": "Myocytes, Cardiac", "descriptor_ui": "D032383", "major_topic": false }, { "descriptor": "Pregnancy", "descriptor_ui": "D011247", "major_topic": false }, { "descriptor": "Time-Lapse Imaging", "descriptor_ui": "D059008", "major_topic": true }, { "descriptor": "Tissue Culture Techniques", "descriptor_ui": "D046509", "major_topic": false }, { "descriptor": "Ubiquitination", "descriptor_ui": "D054875", "major_topic": false } ], "publication": { "conference_name": null, "date": "2014 Jul", "date_precision": "unknown", "issue": "", "normalized_date": null, "pages": "241-249", "proceedings_title": null, "publisher": "", "title": "Journal of molecular and cellular cardiology", "volume": "72", "year": 2014 }, "ssbd": { "database": [], "repository": [] }, "title": "Time-lapse imaging of cell cycle dynamics during development in living cardiomyocyte.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Mammalian embryos develop in coordination with extraembryonic tissues, which support embryonic development by implanting embryos into the uterus, supplying nutrition, providing a confined niche, and also providing patterning signals to embryos. Here, we show that in mouse embryos, the expansion of the amniotic cavity (AC), which is formed between embryonic and extraembryonic tissues, provides the mechanical forces required for a type of morphogenetic movement of the notochord known as convergent extension (CE) in which the cells converge to the midline and the tissue elongates along the antero-posterior (AP) axis. The notochord is stretched along the AP axis, and the expansion of the AC is required for CE. Both mathematical modeling and physical simulation showed that a rectangular morphology of the early notochord caused the application of anisotropic force along the AP axis to the notochord through the isotropic expansion of the AC. AC expansion acts upstream of planar cell polarity (PCP) signaling, which regulates CE movement. Our results highlight the importance of extraembryonic tissues as a source of the forces that control the morphogenesis of embryos.", "classifications": [ { "id": "Eiraku", "label": "Group Eiraku", "parent": "Eiraku", "type": "group" }, { "id": "Eiraku", "label": "Team Eiraku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yu", "last_name": "Imuta", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Koyama", "name": null }, { "creator_type": "author", "first_name": "Dongbo", "last_name": "Shi", "name": null }, { "creator_type": "author", "first_name": "Mototsugu", "last_name": "Eiraku", "name": null }, { "creator_type": "author", "first_name": "Toshihiko", "last_name": "Fujimori", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Sasaki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.mod.2014.01.004" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "24509350" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Body Patterning", "descriptor_ui": "D019521", "major_topic": false }, { "descriptor": "Cell Movement", "descriptor_ui": "D002465", "major_topic": false }, { "descriptor": "Cell Polarity", "descriptor_ui": "D016764", "major_topic": false }, { "descriptor": "Embryo, Mammalian", "descriptor_ui": "D004622", "major_topic": false }, { "descriptor": "Embryonic Development", "descriptor_ui": "D047108", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Morphogenesis", "descriptor_ui": "D009024", "major_topic": false }, { "descriptor": "Notochord", "descriptor_ui": "D009672", "major_topic": false } ], "publication": { "conference_name": null, "date": "2014 May", "date_precision": "unknown", "issue": "", "normalized_date": null, "pages": "44-58", "proceedings_title": null, "publisher": "", "title": "Mechanisms of development", "volume": "132", "year": 2014 }, "ssbd": { "database": [], "repository": [] }, "title": "Mechanical control of notochord morphogenesis by extra-embryonic tissues in mouse embryos.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Somites, metameric structures, give rise to the vertebral column, ribs, skeletal muscles and subcutaneous tissues. In mouse embryos, a pair of somites is formed every 2h by segmentation of the anterior parts of the presomitic mesoderm. This periodic event is regulated by a biological clock called the segmentation clock, which involves cyclic expression of the basic helix-loop-helix gene Hes7. Hes7 oscillation is regulated by negative feedback with a delayed timing. This process has been mathematically simulated by differential-delay equations, which predict that negative feedback with shorter delays would abolish oscillations or produce dampened but more rapid oscillations. We found that reducing the number of introns within the Hes7 gene shortens the delay and abolishes Hes7 oscillation or results in a more rapid tempo of Hes7 oscillation, increasing the number of somites and vertebrae in the cervical and upper thoracic region. We also found that Hes1, a Hes7-related gene, is expressed in an oscillatory manner by many cell types, including fibroblasts and neural stem cells. In these cells, Hes1 expression oscillates with a period of about 2-3h, and this oscillation is important for cell cycle progression. Furthermore, in neural stem cells, Hes1 oscillation drives cyclic expression of the proneural genes Ascl1 and Neurogenin2 and regulates multipotency. Hes1 expression oscillates more slowly in embryonic stem cells, and Hes1 oscillation regulates their fate preferences. Taken together, these results suggest that oscillatory expression with short periods (ultradian oscillation) is important for many biological events.", "classifications": [ { "id": "Imayoshi", "label": "Group Imayoshi", "parent": "Imayoshi", "type": "group" }, { "id": "Imayoshi", "label": "Team Imayoshi", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yukiko", "last_name": "Harima", "name": null }, { "creator_type": "author", "first_name": "Itaru", "last_name": "Imayoshi", "name": null }, { "creator_type": "author", "first_name": "Hiromi", "last_name": "Shimojo", "name": null }, { "creator_type": "author", "first_name": "Taeko", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Ryoichiro", "last_name": "Kageyama", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.semcdb.2014.04.038" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "24865153" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Basic Helix-Loop-Helix Proteins", "descriptor_ui": "D051792", "major_topic": false }, { "descriptor": "Circadian Rhythm", "descriptor_ui": "D002940", "major_topic": false }, { "descriptor": "Feedback, Physiological", "descriptor_ui": "D025461", "major_topic": false }, { "descriptor": "Gene Expression Regulation", "descriptor_ui": "D005786", "major_topic": false }, { "descriptor": "Homeodomain Proteins", "descriptor_ui": "D018398", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Neural Stem Cells", "descriptor_ui": "D058953", "major_topic": false }, { "descriptor": "Protein Stability", "descriptor_ui": "D055550", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Transcription Factor HES-1", "descriptor_ui": "D000072056", "major_topic": false } ], "publication": { "conference_name": null, "date": "2014 Oct", "date_precision": "unknown", "issue": "", "normalized_date": null, "pages": "85-90", "proceedings_title": null, "publisher": "", "title": "Seminars in cell & developmental biology", "volume": "34", "year": 2014 }, "ssbd": { "database": [], "repository": [] }, "title": "The roles and mechanism of ultradian oscillatory expression of the mouse Hes genes.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "PURPOSE: To evaluate the effects of different drug-delivery techniques for levofloxacin (LVFX) in ocular penetration and the prevention of endophthalmitis using an aphakic rabbit model with posterior capsule rupture (PCR). METHODS: LVFX was administered to aphakic rabbit eyes with or without PCR using eye drops (EDs), subconjunctival injection (SCI), or intracameral (IC) injection. The concentration of the drug in the vitreous and aqueous humors was estimated at 2 h after injection. In another study, aphakic rabbit eyes with PCR were inoculated with Enterococcus faecalis, immediately followed by 0.5% LVFX ED, 0.5% moxifloxacin (MFLX) ED, LVFX IC (500 μg/0.1 mL), or IC saline. EDs were administered 0, 3, and 6 h after surgery. Changes on electroretinography (ERG) and intraocular bacterial growth were determined sequentially until 48 h after inoculation. RESULTS: The concentrations of LVFX at 2 h after IC were higher in the aqueous humor and the vitreous cavity of eyes with or without PCR, compared with EDs or SCI. Eyes treated with LVFX ED, MFLX ED, or IC saline showed a significantly greater reduction in b-wave amplitude on ERG at 48 h compared with eyes treated with LVFX IC. The number of bacteria recovered from the vitreous humor in eyes treated with IC LVFX at 48 h was significantly less than from eyes that received other treatments. CONCLUSION: The LVFX IC was effective at suppressing endophthalmitis caused by E. faecalis in eyes with a PCR.", "classifications": [ { "id": "Suzuki", "label": "Group Suzuki", "parent": "Takekawa", "type": "group" }, { "id": "Takekawa", "label": "Team Takekawa", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Takahiro", "last_name": "Uda", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Arisa", "last_name": "Mitani", "name": null }, { "creator_type": "author", "first_name": "Yoshitaka", "last_name": "Tasaka", "name": null }, { "creator_type": "author", "first_name": "Shiro", "last_name": "Kawasaki", "name": null }, { "creator_type": "author", "first_name": "Tsuyoshi", "last_name": "Mito", "name": null }, { "creator_type": "author", "first_name": "Yuichi", "last_name": "Ohashi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1089/jop.2013.0204" }, "pmcid": { "normalized": "PMC4012624" }, "pmid": { "normalized": "24410272" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Anti-Bacterial Agents", "descriptor_ui": "D000900", "major_topic": false }, { "descriptor": "Aqueous Humor", "descriptor_ui": "D001082", "major_topic": false }, { "descriptor": "Drug Delivery Systems", "descriptor_ui": "D016503", "major_topic": false }, { "descriptor": "Endophthalmitis", "descriptor_ui": "D009877", "major_topic": false }, { "descriptor": "Enterococcus faecalis", "descriptor_ui": "D013293", "major_topic": false }, { "descriptor": "Eye Infections, Bacterial", "descriptor_ui": "D015818", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Fluoroquinolones", "descriptor_ui": "D024841", "major_topic": false }, { "descriptor": "Gram-Positive Bacterial Infections", "descriptor_ui": "D016908", "major_topic": false }, { "descriptor": "Levofloxacin", "descriptor_ui": "D064704", "major_topic": false }, { "descriptor": "Moxifloxacin", "descriptor_ui": "D000077266", "major_topic": false }, { "descriptor": "Ophthalmic Solutions", "descriptor_ui": "D009883", "major_topic": false }, { "descriptor": "Posterior Capsular Rupture, Ocular", "descriptor_ui": "D057851", "major_topic": false }, { "descriptor": "Rabbits", "descriptor_ui": "D011817", "major_topic": false }, { "descriptor": "Vitreous Body", "descriptor_ui": "D014822", "major_topic": false } ], "publication": { "conference_name": null, "date": "2014 May", "date_precision": "unknown", "issue": "4", "normalized_date": null, "pages": "333-339", "proceedings_title": null, "publisher": "", "title": "Journal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics", "volume": "30", "year": 2014 }, "ssbd": { "database": [], "repository": [] }, "title": "Ocular penetration and efficacy of levofloxacin using different drug-delivery techniques for the prevention of endophthalmitis in rabbit eyes with posterior capsule rupture.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Microtubules (MTs) have been implicated in regulating the directionality and expansion of polarized growth. Using the moss Physcomitrella patens, this work describes how dynamic MT bundles form cyclically in the polarized expansion zone through the coalescence of growing MT plus ends and how plant-specific kinesins regulate the turnover of the MT bundles as well as the directionality and rate of cell growth.", "classifications": [ { "id": "Sato", "label": "Group Sato", "parent": "Tsuchiya", "type": "group" }, { "id": "Tsuchiya", "label": "Team Tsuchiya", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yuji", "last_name": "Hiwatashi", "name": null }, { "creator_type": "author", "first_name": "Yoshikatsu", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "John H.", "last_name": "Doonan", "name": null } ], "identifiers": { "doi": { "normalized": "10.1105/tpc.113.121723" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "24642939" } }, "mesh": [ { "descriptor": "Bryopsida", "descriptor_ui": "D019068", "major_topic": false }, { "descriptor": "Cytokinesis", "descriptor_ui": "D048749", "major_topic": false }, { "descriptor": "Kinesins", "descriptor_ui": "D016547", "major_topic": false }, { "descriptor": "Microtubules", "descriptor_ui": "D008870", "major_topic": false }, { "descriptor": "Molecular Sequence Data", "descriptor_ui": "D008969", "major_topic": false } ], "publication": { "conference_name": null, "date": "2014 Mar", "date_precision": "unknown", "issue": "3", "normalized_date": null, "pages": "1256-1266", "proceedings_title": null, "publisher": "", "title": "The Plant Cell", "volume": "26", "year": 2014 }, "ssbd": { "database": [], "repository": [] }, "title": "Kinesins Have a Dual Function in Organizing Microtubules during Both Tip Growth and Cytokinesis in Physcomitrella patens[W][OPEN].", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "In this review, we introduce the principles of spatial resolution improvement in super-resolution microscopies that were recently developed. These super-resolution techniques utilize the interaction of light and fluorescent probes in order to break the diffraction barrier that limits spatial resolution. The imaging property of each super-resolution technique is also compared with the corresponding conventional one. Typical applications of the super-resolution techniques in biological research are also introduced.", "classifications": [ { "id": "Fujita", "label": "Group Fujita", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Masahito", "last_name": "Yamanaka", "name": null }, { "creator_type": "author", "first_name": "Nicholas I.", "last_name": "Smith", "name": null }, { "creator_type": "author", "first_name": "Katsumasa", "last_name": "Fujita", "name": null } ], "identifiers": { "doi": { "normalized": "10.1093/jmicro/dfu007" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "24671128" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Microscopy", "descriptor_ui": "D008853", "major_topic": false }, { "descriptor": "Microscopy, Confocal", "descriptor_ui": "D018613", "major_topic": false }, { "descriptor": "Microscopy, Fluorescence", "descriptor_ui": "D008856", "major_topic": false }, { "descriptor": "Organelles", "descriptor_ui": "D015388", "major_topic": false } ], "publication": { "conference_name": null, "date": "2014 Jun", "date_precision": "unknown", "issue": "3", "normalized_date": null, "pages": "177-192", "proceedings_title": null, "publisher": "", "title": "Microscopy (Oxford, England)", "volume": "63", "year": 2014 }, "ssbd": { "database": [], "repository": [] }, "title": "Introduction to super-resolution microscopy.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Aphid infestations can cause severe decreases in soybean (Glycine max [L.] Merr.) yield. Since planting aphid-resistant soybean strains is a promising approach for pest control, understanding the resistance mechanisms employed by aphids is of considerable importance. We compared aphid resistance in seven soybean strains and found that strain Tohoku149 was the most resistant to the foxglove aphid, Aulacorthum solani Kaltenbach. We subsequently analyzed the metabolite profiles of aphids cultured on the leaves of resistant and susceptible soybean strains using capillary electrophoresis-time-of-flight mass spectrometry. Our findings showed that the metabolite profiles of several amino acids, glucose 6-phosphate, and components of the tricarboxylic acid cycle were similar in aphids reared on Tohoku149 leaves and in aphids maintained under conditions of starvation, suggesting that Tohoku149 is more resistant to aphid feeding. Compared to susceptible strains, we also found that two methylated metabolites, S-methylmethionine and trigonelline, were either not detected or decreased in aphids reared on Tohoku149 plants. Since these metabolites function as important sulfur transporters in phloem sap and osmoprotectants involved in salt and drought stress, respectively, aphid-resistance is considered to be related to sulfur metabolism and methylation. These results contribute to an increase in our understanding of soybean aphid resistance mechanisms at the molecular level.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Dan", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Sugimoto", "name": null }, { "creator_type": "author", "first_name": "Hiromichi", "last_name": "Akashi", "name": null }, { "creator_type": "author", "first_name": "Masaru", "last_name": "Tomita", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null } ], "identifiers": { "doi": { "normalized": "10.1039/c3mb70595a" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "24514152" } }, "mesh": [ { "descriptor": "Alkaloids", "descriptor_ui": "D000470", "major_topic": false }, { "descriptor": "Amino Acids", "descriptor_ui": "D000596", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Aphids", "descriptor_ui": "D001042", "major_topic": false }, { "descriptor": "Biological Transport", "descriptor_ui": "D001692", "major_topic": false }, { "descriptor": "Energy Metabolism", "descriptor_ui": "D004734", "major_topic": false }, { "descriptor": "Gene Expression Profiling", "descriptor_ui": "D020869", "major_topic": false }, { "descriptor": "Glycine max", "descriptor_ui": "D013025", "major_topic": false }, { "descriptor": "Mass Spectrometry", "descriptor_ui": "D013058", "major_topic": false }, { "descriptor": "Methylation", "descriptor_ui": "D008745", "major_topic": false }, { "descriptor": "Pest Control", "descriptor_ui": "D010571", "major_topic": false }, { "descriptor": "Plant Leaves", "descriptor_ui": "D018515", "major_topic": false }, { "descriptor": "Sulfur", "descriptor_ui": "D013455", "major_topic": false }, { "descriptor": "Vitamin U", "descriptor_ui": "D014814", "major_topic": false } ], "publication": { "conference_name": null, "date": "2014 Apr", "date_precision": "unknown", "issue": "4", "normalized_date": null, "pages": "909-915", "proceedings_title": null, "publisher": "", "title": "Molecular bioSystems", "volume": "10", "year": 2014 }, "ssbd": { "database": [], "repository": [] }, "title": "Comparative metabolite profiling of foxglove aphids (Aulacorthum solani Kaltenbach) on leaves of resistant and susceptible soybean strains.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "p62/SQSTM1 (p62) is a multifunctional protein implicated in several signal transduction pathways and selectively degraded by autophagy, a process for lysosomal degradation of both protein and organelle. p62 was also recently reported to be overexpressed in various malignancies and its inhibition to suppress carcinoma cell proliferation. However, its correlation with autophagy in carcinoma cells has remained largely unknown. Therefore, in this study, we examined the effects of p62 inhibition on the regulation of autophagy and cell survival in p62-positive carcinoma cells. p62-silencing dramatically suppressed cell proliferation and induced autophagy in p62 expressing PC9 and A549 cells. Electron microscopical analysis revealed the formation of autophagosomes with multilayer membranes caused by p62-silencing. p62 silencing-mediated reduced cell viability was restored by both genomic and pharmacological inhibition of autophagy but not that of apoptosis. These findings were also detected in several types of carcinoma cell lines including adenocarcinomas and squamous cell carcinomas. Results of our present study revealed that an inhibition of p62 resulted in the formation of mis-regulated autophagosomes with multilayer membranes and an autophagic cell death, and p62 can therefore be an attractive target for the development of anti-neoplastic agents.", "classifications": [ { "id": "Suzuki", "label": "Group Suzuki", "parent": "Takekawa", "type": "group" }, { "id": "Takekawa", "label": "Team Takekawa", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Kaito", "last_name": "Nihira", "name": null }, { "creator_type": "author", "first_name": "Yasuhiro", "last_name": "Miki", "name": null }, { "creator_type": "author", "first_name": "Katsuhiko", "last_name": "Ono", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Hironobu", "last_name": "Sasano", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/cas.12396" }, "pmcid": { "normalized": "PMC4317843" }, "pmid": { "normalized": "24618016" } }, "mesh": [ { "descriptor": "Adaptor Proteins, Signal Transducing", "descriptor_ui": "D048868", "major_topic": false }, { "descriptor": "Autophagy", "descriptor_ui": "D001343", "major_topic": false }, { "descriptor": "Autophagy-Related Protein 5", "descriptor_ui": "D000071187", "major_topic": false }, { "descriptor": "Autophagy-Related Protein 7", "descriptor_ui": "D000071193", "major_topic": false }, { "descriptor": "Carcinoma", "descriptor_ui": "D002277", "major_topic": false }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Cell Proliferation", "descriptor_ui": "D049109", "major_topic": false }, { "descriptor": "Gene Silencing", "descriptor_ui": "D020868", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Microtubule-Associated Proteins", "descriptor_ui": "D008869", "major_topic": false }, { "descriptor": "RNA Interference", "descriptor_ui": "D034622", "major_topic": false }, { "descriptor": "RNA, Small Interfering", "descriptor_ui": "D034741", "major_topic": false }, { "descriptor": "Sequestosome-1 Protein", "descriptor_ui": "D000071456", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Ubiquitin-Activating Enzymes", "descriptor_ui": "D044764", "major_topic": false } ], "publication": { "conference_name": null, "date": "2014 May", "date_precision": "unknown", "issue": "5", "normalized_date": null, "pages": "568-575", "proceedings_title": null, "publisher": "", "title": "Cancer science", "volume": "105", "year": 2014 }, "ssbd": { "database": [], "repository": [] }, "title": "An inhibition of p62/SQSTM1 caused autophagic cell death of several human carcinoma cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "In multicellular organism development, a stochastic cellular response is observed, even when a population of cells is exposed to the same environmental conditions. Retrieving the spatiotemporal regulatory mode hidden in the heterogeneous cellular behavior is a challenging task. The G1/S transition observed in cell cycle progression is a highly stochastic process. By taking advantage of a fluorescence cell cycle indicator, Fucci technology, we aimed to unveil a hidden regulatory mode of cell cycle progression in developing zebrafish. Fluorescence live imaging of Cecyil, a zebrafish line genetically expressing Fucci, demonstrated that newly formed notochordal cells from the posterior tip of the embryonic mesoderm exhibited the red (G1) fluorescence signal in the developing notochord. Prior to their initial vacuolation, these cells showed a fluorescence color switch from red to green, indicating G1/S transitions. This G1/S transition did not occur in a synchronous manner, but rather exhibited a stochastic process, since a mixed population of red and green cells was always inserted between newly formed red (G1) notochordal cells and vacuolating green cells. We termed this mixed population of notochordal cells, the G1/S transition window. We first performed quantitative analyses of live imaging data and a numerical estimation of the probability of the G1/S transition, which demonstrated the existence of a posteriorly traveling regulatory wave of the G1/S transition window. To obtain a better understanding of this regulatory mode, we constructed a mathematical model and performed a model selection by comparing the results obtained from the models with those from the experimental data. Our analyses demonstrated that the stochastic G1/S transition window in the notochord travels posteriorly in a periodic fashion, with doubled the periodicity of the neighboring paraxial mesoderm segmentation. This approach may have implications for the characterization of the pathophysiological tissue growth mode.", "classifications": [ { "id": "Sawano", "label": "Group Sawano", "parent": "Shintaku", "type": "group" }, { "id": "Shintaku", "label": "Team Shintaku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Mayu", "last_name": "Sugiyama", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Saitou", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Kurokawa", "name": null }, { "creator_type": "author", "first_name": "Asako", "last_name": "Sakaue-Sawano", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Imamura", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Miyawaki", "name": null }, { "creator_type": "author", "first_name": "Tadahiro", "last_name": "Iimura", "name": null } ], "identifiers": { "doi": { "normalized": "10.1371/journal.pcbi.1003957" }, "pmcid": { "normalized": "PMC4256085" }, "pmid": { "normalized": "25474567" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Cycle", "descriptor_ui": "D002453", "major_topic": false }, { "descriptor": "Computational Biology", "descriptor_ui": "D019295", "major_topic": false }, { "descriptor": "Computer Simulation", "descriptor_ui": "D003198", "major_topic": false }, { "descriptor": "Embryo, Nonmammalian", "descriptor_ui": "D004625", "major_topic": false }, { "descriptor": "Embryonic Development", "descriptor_ui": "D047108", "major_topic": false }, { "descriptor": "Microscopy, Fluorescence", "descriptor_ui": "D008856", "major_topic": false }, { "descriptor": "Models, Biological", "descriptor_ui": "D008954", "major_topic": true }, { "descriptor": "Zebrafish", "descriptor_ui": "D015027", "major_topic": false } ], "publication": { "conference_name": null, "date": "2014 Dec", "date_precision": "unknown", "issue": "12", "normalized_date": null, "pages": "e1003957", "proceedings_title": null, "publisher": "", "title": "PLoS computational biology", "volume": "10", "year": 2014 }, "ssbd": { "database": [], "repository": [] }, "title": "Live imaging-based model selection reveals periodic regulation of the stochastic G1/S phase transition in vertebrate axial development.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Poorly-differentiated colorectal cancers (PD-CRC) show high metastatic potential and poor prognosis. However, molecular characteristics of PD-CRC remain unknown to date, particularly in molecular targeting therapy for patients with PD-CRC. In this study, we examined the expression of EGFR, HER2 and HER3 in PD-CRC by immunohistochemical analysis of archived clinical specimens of primary tumors and investigated the sensitivity of PD-CRC cell lines to gefitinib, a tyrosine kinase inhibitor for EGFR in vitro. We found that HER3 expression of PD-CRC among members of the HER family was significantly lower than that of well to moderately differentiated CRC (WMD-CRC) and 37% of the PD cases showed a EGFR+/HER2+/HER3- expression pattern. COLM-5 cells, a PD-CRC-derived cell line, which exhibits EGFR+/HER2+/HER3- expression pattern and recapitulates the typical histology of PD-CRC in xenografted tumors, showed high gefitinib sensitivity both in vitro and in vivo, compared with WMD-CRC cell line (COLM-2). Treatment with gefitinib resulted in the upregulation of p27Kip1 expression and induction of G1 cell cycle arrest, concomitantly associated with inactivation of PI3K/Akt signaling in COLM-5 cells and marked inhibition of xenografted tumors in nude mice, but not evident in COLM-2 cells. Treatment with sodium butyrate, an HDAC inhibitor that induces differentiation, upregulated the expression of HER3 associated with enhancement of the PI3K/Akt signaling, attenuated gefitinib-mediated p27Kip1 upregulation and reduced gefitinib sensitivity in COLM-5 cells in vitro. Furthermore, enforced expression of HER3 in COLM-5 cells resulted in significant resistance to gefitinib treatment both in vitro and in vivo. These findings suggest that deficient HER3 expression plays an important role in gefitinib sensitivity and that a malignant subset of PD with EGFR+/HER2+/HER3- phenotype is a potential candidate for a target of anti-EGFR molecular therapy such as gefitinib.", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Susumu", "last_name": "Nakata", "name": null }, { "creator_type": "author", "first_name": "Harunari", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Yuichi", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Masayasu", "last_name": "Hara", "name": null }, { "creator_type": "author", "first_name": "Mitsugu", "last_name": "Fujita", "name": null }, { "creator_type": "author", "first_name": "Eisaku", "last_name": "Kondo", "name": null }, { "creator_type": "author", "first_name": "Yukihide", "last_name": "Kanemitsu", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null }, { "creator_type": "author", "first_name": "Hayao", "last_name": "Nakanishi", "name": null } ], "identifiers": { "doi": { "normalized": "10.3892/ijo.2014.2538" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "25017791" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Antineoplastic Agents", "descriptor_ui": "D000970", "major_topic": false }, { "descriptor": "Butyric Acid", "descriptor_ui": "D020148", "major_topic": false }, { "descriptor": "Cell Cycle", "descriptor_ui": "D002453", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Colorectal Neoplasms", "descriptor_ui": "D015179", "major_topic": false }, { "descriptor": "Erb-b2 Receptor Tyrosine Kinases", "descriptor_ui": "D018719", "major_topic": false }, { "descriptor": "ErbB Receptors", "descriptor_ui": "D066246", "major_topic": false }, { "descriptor": "Gefitinib", "descriptor_ui": "D000077156", "major_topic": false }, { "descriptor": "Gene Expression Regulation, Neoplastic", "descriptor_ui": "D015972", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Nude", "descriptor_ui": "D008819", "major_topic": false }, { "descriptor": "Quinazolines", "descriptor_ui": "D011799", "major_topic": false }, { "descriptor": "Receptor, ErbB-3", "descriptor_ui": "D020893", "major_topic": false }, { "descriptor": "Xenograft Model Antitumor Assays", "descriptor_ui": "D023041", "major_topic": false } ], "publication": { "conference_name": null, "date": "2014 Oct", "date_precision": "unknown", "issue": "4", "normalized_date": null, "pages": "1583-1593", "proceedings_title": null, "publisher": "", "title": "International journal of oncology", "volume": "45", "year": 2014 }, "ssbd": { "database": [], "repository": [] }, "title": "Deficient HER3 expression in poorly-differentiated colorectal cancer cells enhances gefitinib sensitivity.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Structural and morphological changes of the cardiovascular systems (cardiovascular remodeling) are a major clinical outcome of cardiovascular diseases. Many lines of evidences have implied that transfiguration of reduction/oxidation (redox) homeostasis due to excess production of reactive oxygen species (ROS) and/or ROS-derived electrophilic metabolites (electrophiles) is the main cause of cardiovascular remodeling. Gasotransmitters, such as nitric oxide (NO) and endogenous electrophiles, are considered major bioactive species and have been extensively studied in the context of physiological and pathological cardiovascular events. We have recently found that hydrogen sulfide-related reactive species function as potent nucleophiles to eliminate electrophilic modification of signaling proteins induced by NO-derived electrophilic byproducts (e.g., 8-nitroguanosine 3',5'-cyclic monophosphate and nitro-oleic acid). In this review, we discuss the current understanding of redox control of cardiovascular pathophysiology by electrophiles and nucleophiles. We propose that modulation of electrophile-mediated post-translational modification of protein cysteine thiols may be a new therapeutic strategy of cardiovascular diseases. This article is part of a Special Issue entitled \"Redox Signalling in the Cardiovascular System\".", "classifications": [ { "id": "Akaike", "label": "Group Akaike", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Group Nishida", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Motohiro", "last_name": "Nishida", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Toyama", "name": null }, { "creator_type": "author", "first_name": "Takaaki", "last_name": "Akaike", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.yjmcc.2014.02.003" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "24530900" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cyclic GMP", "descriptor_ui": "D006152", "major_topic": false }, { "descriptor": "GTP-Binding Proteins", "descriptor_ui": "D019204", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Oxidation-Reduction", "descriptor_ui": "D010084", "major_topic": false }, { "descriptor": "Reactive Oxygen Species", "descriptor_ui": "D017382", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false } ], "publication": { "conference_name": null, "date": "2014 Aug", "date_precision": "unknown", "issue": "", "normalized_date": null, "pages": "10-17", "proceedings_title": null, "publisher": "", "title": "Journal of molecular and cellular cardiology", "volume": "73", "year": 2014 }, "ssbd": { "database": [], "repository": [] }, "title": "Role of 8-nitro-cGMP and its redox regulation in cardiovascular electrophilic signaling.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "OBJECTIVE: Visceral fat accumulation and metabolic syndrome incidence among women increase after menopause; therefore, fat metabolic changes and fat redistribution may occur according to menstrual status. The aim of our study was to clarify differences in subcutaneous and visceral adipose tissue metabolism between premenopausal and postmenopausal women, using metabolomics. METHODS: Thirty-nine (16 premenopausal and 23 postmenopausal) women were recruited through elective gynecologic surgery, and both subcutaneous and visceral adipose tissues were collected during surgical operation. Metabolite profiling of adipose tissue was performed by capillary electrophoresis with electrospray ionization time-of-flight mass spectrometry. RESULTS: Sedoheptulose 7-phosphate, a midproduct of the pentose phosphate pathway, was significantly higher (P < 0.05) in visceral adipose tissues of premenopausal women. Dihydroxyacetone phosphate and fructose-1,6-biphosphate, midproducts of glycolysis, were significantly higher (P < 0.05) in subcutaneous adipose tissues of postmenopausal women. The concentrations of fatty acid metabolites-heptanoate (C7:0; premenopausal vs postmenopausal, 4.07 [0.72] vs 2.64 [0.28] nmol/g), octanoate (C8:0; 3.52 [0.29] vs 5.20 [0.29] nmol/g), and pelargonate (C9:0; 8.03 [0.49] vs 10.66 [0.44] nmol/g)-in the visceral fat (but not in subcutaneous fat) of postmenopausal women were significantly higher (P < 0.05) than those in the visceral fat of premenopausal women. CONCLUSIONS: Fatty acid metabolites increase in visceral fat (but not in subcutaneous fat) after menopause. The change in fatty acid metabolism in visceral adipose tissues might be related to metabolic syndrome in postmenopausal women.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Hizuru", "last_name": "Yamatani", "name": null }, { "creator_type": "author", "first_name": "Kazuhiro", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Takayuki", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Hirohisa", "last_name": "Kurachi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1097/gme.0b013e318296431a" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "23760430" } }, "mesh": [ { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Body Composition", "descriptor_ui": "D001823", "major_topic": false }, { "descriptor": "Cytokines", "descriptor_ui": "D016207", "major_topic": false }, { "descriptor": "Dihydroxyacetone Phosphate", "descriptor_ui": "D004099", "major_topic": false }, { "descriptor": "Estradiol", "descriptor_ui": "D004958", "major_topic": false }, { "descriptor": "Fatty Acids", "descriptor_ui": "D005227", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Fructosediphosphates", "descriptor_ui": "D005635", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Intra-Abdominal Fat", "descriptor_ui": "D050152", "major_topic": false }, { "descriptor": "Macrophages", "descriptor_ui": "D008264", "major_topic": false }, { "descriptor": "Metabolic Syndrome", "descriptor_ui": "D024821", "major_topic": false }, { "descriptor": "Metabolomics", "descriptor_ui": "D055432", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Postmenopause", "descriptor_ui": "D017698", "major_topic": false }, { "descriptor": "Premenopause", "descriptor_ui": "D017697", "major_topic": false }, { "descriptor": "Subcutaneous Fat", "descriptor_ui": "D050151", "major_topic": false }, { "descriptor": "Sugar Phosphates", "descriptor_ui": "D013403", "major_topic": false } ], "publication": { "conference_name": null, "date": "2014 Feb", "date_precision": "unknown", "issue": "2", "normalized_date": null, "pages": "170-176", "proceedings_title": null, "publisher": "", "title": "Menopause (New York, N.Y.)", "volume": "21", "year": 2014 }, "ssbd": { "database": [], "repository": [] }, "title": "Differences in the fatty acid metabolism of visceral adipose tissue in postmenopausal women.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "In order to describe two-dimensionally packed cells in epithelial tissues both mathematically and physically, there have been developed several sorts of geometrical models, such as the vertex model, the finite element model, the cell-centered model, and the cellular Potts model. So far, in any case, pressures have not neatly been dealt with and the curvatures of the cell boundaries have been even omitted through their approximations. We focus on these quantities and formulate them in the vertex model. Thus, a model with the curvatures is constructed, and its algorithm for simulation is provided. The possible extensions and applications of this model are also discussed.", "classifications": [ { "id": "Morishita", "label": "Group Morishita", "parent": "Morishita", "type": "group" }, { "id": "Morishita", "label": "Team Morishita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yukitaka", "last_name": "Ishimoto", "name": null }, { "creator_type": "author", "first_name": "Yoshihiro", "last_name": "Morishita", "name": null } ], "identifiers": { "doi": { "normalized": "10.1103/physreve.90.052711" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "25493820" } }, "mesh": [], "publication": { "conference_name": null, "date": "2014 Nov", "date_precision": "unknown", "issue": "5-1", "normalized_date": null, "pages": "052711", "proceedings_title": null, "publisher": "", "title": "Physical review. E, Statistical, nonlinear, and soft matter physics", "volume": "90", "year": 2014 }, "ssbd": { "database": [], "repository": [] }, "title": "Bubbly vertex dynamics: A dynamical and geometrical model for epithelial tissues with curved cell shapes.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Identification of genes influencing a phenotype of interest is frequently achieved through genetic screening by RNA interference (RNAi) or knockouts. However, RNAi may only achieve partial depletion of gene activity, and knockout-based screens are difficult in diploid mammalian cells. Here we took advantage of the efficiency and high throughput of genome editing based on type II, clustered, regularly interspaced, short palindromic repeats (CRISPR)-CRISPR-associated (Cas) systems to introduce genome-wide targeted mutations in mouse embryonic stem cells (ESCs). We designed 87,897 guide RNAs (gRNAs) targeting 19,150 mouse protein-coding genes and used a lentiviral vector to express these gRNAs in ESCs that constitutively express Cas9. Screening the resulting ESC mutant libraries for resistance to either Clostridium septicum alpha-toxin or 6-thioguanine identified 27 known and 4 previously unknown genes implicated in these phenotypes. Our results demonstrate the potential for efficient loss-of-function screening using the CRISPR-Cas9 system.", "classifications": [ { "id": "Yusa", "label": "Group Yusa", "parent": "Eiraku", "type": "group" }, { "id": "Eiraku", "label": "Team Eiraku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Hiroko", "last_name": "Koike-Yusa", "name": null }, { "creator_type": "author", "first_name": "Yilong", "last_name": "Li", "name": null }, { "creator_type": "author", "first_name": "E.-Pien", "last_name": "Tan", "name": null }, { "creator_type": "author", "first_name": "Martin Del Castillo", "last_name": "Velasco-Herrera", "name": null }, { "creator_type": "author", "first_name": "Kosuke", "last_name": "Yusa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/nbt.2800" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "24535568" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Biotechnology", "descriptor_ui": "D001709", "major_topic": false }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Clustered Regularly Interspaced Short Palindromic Repeats", "descriptor_ui": "D064112", "major_topic": false }, { "descriptor": "CRISPR-Cas Systems", "descriptor_ui": "D064113", "major_topic": false }, { "descriptor": "Embryonic Stem Cells", "descriptor_ui": "D053595", "major_topic": false }, { "descriptor": "Gene Library", "descriptor_ui": "D015723", "major_topic": false }, { "descriptor": "Genome", "descriptor_ui": "D016678", "major_topic": false }, { "descriptor": "Genomics", "descriptor_ui": "D023281", "major_topic": false }, { "descriptor": "Lentivirus", "descriptor_ui": "D016086", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Reproducibility of Results", "descriptor_ui": "D015203", "major_topic": false }, { "descriptor": "RNA Interference", "descriptor_ui": "D034622", "major_topic": false }, { "descriptor": "RNA, Guide, CRISPR-Cas Systems", "descriptor_ui": "D000094704", "major_topic": false } ], "publication": { "conference_name": null, "date": "2014 Mar", "date_precision": "unknown", "issue": "3", "normalized_date": null, "pages": "267-273", "proceedings_title": null, "publisher": "", "title": "Nature biotechnology", "volume": "32", "year": 2014 }, "ssbd": { "database": [], "repository": [] }, "title": "Genome-wide recessive genetic screening in mammalian cells with a lentiviral CRISPR-guide RNA library.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "PURPOSE: To evaluate the effectiveness of topical agents for the treatment of Acanthamoeba keratitis (AK). DESIGN: Laboratory research. PARTICIPANTS: Fifty-six Acanthamoeba isolates from 56 patients with clinically proven AK were studied. METHODS: The effectiveness of 7 agents against Acanthamoeba cysts was determined in vitro. The agents were 1.0% povidone-iodine, 0.05% benzalkonium chloride (BZC), 0.02% chlorhexidine gluconate (CHG), 0.1% propamidine isethionate, 0.02% polyhexamethylene biguanide (PHMB), 5.0% natamycin, and 1.0% voriconazole (VRCZ). These concentrations are those recommended for patients. In addition, 10-fold dilutions of each of the agents were tested. After exposing the cysts to each agent at 35 degrees C for 1 hour or 24 hours, the agents were removed by centrifugal washing. The exposed cysts were observed by optical microscopy for 7 days. In addition, the fine structures of the exposed isolates were examined by transmission electron microscopy (TEM). The genotype of the isolates was determined by 18S rDNA fragment sequencing. MAIN OUTCOME MEASURES: The in vitro susceptibility was determined by complete growth inhibition, and the morphologic appearance was determined by TEM. The genotypes of the 56 isolates were determined by 18S rDNA fragment sequencing. RESULTS: The Acanthamoeba cysts were most susceptible to natamycin, followed by povidone-iodine, BZC, PHMB, propamidine, and CHG. None of the strains was susceptible to VRCZ. The susceptibilities to PHMB and CHG may be time dependent and to propamidine may be concentration dependent. Transmission electron microscopy showed changes in the inner structure of the cysts exposed to natamycin and povidone-iodine. The Acanthamoeba genotype was T4 in 52 isolates, and cysts with the same genotype had different agent susceptibilities. CONCLUSIONS: Natamycin and povidone-iodine had excellent cysti-static (or cystcidal) effects, and PHMB and propamidine did not. There was no correlation between agent effectiveness and Acanthamoeba genotype. Therefore, susceptibility tests of isolates are needed to choose the most appropriate agent, and our results can be a guideline for choosing the most appropriate agent for immediate empirical treatment of AK.", "classifications": [ { "id": "Suzuki", "label": "Group Suzuki", "parent": "Takekawa", "type": "group" }, { "id": "Takekawa", "label": "Team Takekawa", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Atsuko", "last_name": "Sunada", "name": null }, { "creator_type": "author", "first_name": "Keigo", "last_name": "Kimura", "name": null }, { "creator_type": "author", "first_name": "Isao", "last_name": "Nishi", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Toyokawa", "name": null }, { "creator_type": "author", "first_name": "Akiko", "last_name": "Ueda", "name": null }, { "creator_type": "author", "first_name": "Tomomi", "last_name": "Sakata", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Yoshitsugu", "last_name": "Inoue", "name": null }, { "creator_type": "author", "first_name": "Yuichi", "last_name": "Ohashi", "name": null }, { "creator_type": "author", "first_name": "Seishi", "last_name": "Asari", "name": null }, { "creator_type": "author", "first_name": "Yoshinori", "last_name": "Iwatani", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.ophtha.2014.04.013" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "24880905" } }, "mesh": [ { "descriptor": "Acanthamoeba", "descriptor_ui": "D000048", "major_topic": false }, { "descriptor": "Acanthamoeba Keratitis", "descriptor_ui": "D015823", "major_topic": false }, { "descriptor": "Anti-Infective Agents, Local", "descriptor_ui": "D000891", "major_topic": false }, { "descriptor": "Antiprotozoal Agents", "descriptor_ui": "D000981", "major_topic": false }, { "descriptor": "Disinfectants", "descriptor_ui": "D004202", "major_topic": false }, { "descriptor": "DNA, Protozoan", "descriptor_ui": "D016054", "major_topic": false }, { "descriptor": "Genotype", "descriptor_ui": "D005838", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Ophthalmic Solutions", "descriptor_ui": "D009883", "major_topic": false }, { "descriptor": "RNA, Ribosomal, 18S", "descriptor_ui": "D012337", "major_topic": false } ], "publication": { "conference_name": null, "date": "2014 Oct", "date_precision": "unknown", "issue": "10", "normalized_date": null, "pages": "2059-2065", "proceedings_title": null, "publisher": "", "title": "Ophthalmology", "volume": "121", "year": 2014 }, "ssbd": { "database": [], "repository": [] }, "title": "In vitro evaluations of topical agents to treat Acanthamoeba keratitis.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "This protocol describes how to observe gastrulation in living mouse embryos by using light-sheet microscopy and computational tools to analyze the resulting image data at the single-cell level. We describe a series of techniques needed to image the embryos under physiological conditions, including how to hold mouse embryos without agarose embedding, how to transfer embryos without air exposure and how to construct environmental chambers for live imaging by digital scanned light-sheet microscopy (DSLM). Computational tools include manual and semiautomatic tracking programs that are developed for analyzing the large 4D data sets acquired with this system. Note that this protocol does not include details of how to build the light-sheet microscope itself. Time-lapse imaging ends within 12 h, with subsequent tracking analysis requiring 3-6 d. Other than some mouse-handling skills, this protocol requires no advanced skills or knowledge. Light-sheet microscopes are becoming more widely available, and thus the techniques outlined in this paper should be helpful for investigating mouse embryogenesis.", "classifications": [ { "id": "Mochizuki", "label": "Group Mochizuki", "parent": "Eiraku", "type": "group" }, { "id": "Eiraku", "label": "Team Eiraku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Takehiko", "last_name": "Ichikawa", "name": null }, { "creator_type": "author", "first_name": "Kenichi", "last_name": "Nakazato", "name": null }, { "creator_type": "author", "first_name": "Philipp J.", "last_name": "Keller", "name": null }, { "creator_type": "author", "first_name": "Hiroko", "last_name": "Kajiura-Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Ernst H. K.", "last_name": "Stelzer", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Mochizuki", "name": null }, { "creator_type": "author", "first_name": "Shigenori", "last_name": "Nonaka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/nprot.2014.035" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "24525751" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Embryo, Mammalian", "descriptor_ui": "D004622", "major_topic": false }, { "descriptor": "Gastrulation", "descriptor_ui": "D054262", "major_topic": false }, { "descriptor": "Imaging, Three-Dimensional", "descriptor_ui": "D021621", "major_topic": false }, { "descriptor": "Immobilization", "descriptor_ui": "D007103", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Microscopy", "descriptor_ui": "D008853", "major_topic": false }, { "descriptor": "Single-Cell Analysis", "descriptor_ui": "D059010", "major_topic": false }, { "descriptor": "Specimen Handling", "descriptor_ui": "D013048", "major_topic": false } ], "publication": { "conference_name": null, "date": "2014 Mar", "date_precision": "unknown", "issue": "3", "normalized_date": null, "pages": "575-585", "proceedings_title": null, "publisher": "", "title": "Nature protocols", "volume": "9", "year": 2014 }, "ssbd": { "database": [], "repository": [] }, "title": "Live imaging and quantitative analysis of gastrulation in mouse embryos using light-sheet microscopy and 3D tracking tools.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Hydrogen sulfide (H2S) is an endogenously generated and putative signaling/effector molecule. Despite its numerous reported functions, the chemistry by which it elicits its functions is not understood. Moreover, recent studies allude to the existence of other sulfur species besides H2S that may play critical physiological roles. Herein, the basic chemical biology of H2S as well as other related or derived species is discussed and reviewed. This review particularly focuses on the per- and polysulfides which are likely in equilibrium with free H2S and which may be important biological effectors themselves.", "classifications": [ { "id": "Akaike", "label": "Group Akaike", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Katsuhiko", "last_name": "Ono", "name": null }, { "creator_type": "author", "first_name": "Takaaki", "last_name": "Akaike", "name": null }, { "creator_type": "author", "first_name": "Tomohiro", "last_name": "Sawa", "name": null }, { "creator_type": "author", "first_name": "Yoshito", "last_name": "Kumagai", "name": null }, { "creator_type": "author", "first_name": "David A.", "last_name": "Wink", "name": null }, { "creator_type": "author", "first_name": "Dean J.", "last_name": "Tantillo", "name": null }, { "creator_type": "author", "first_name": "Adrian J.", "last_name": "Hobbs", "name": null }, { "creator_type": "author", "first_name": "Peter", "last_name": "Nagy", "name": null }, { "creator_type": "author", "first_name": "Ming", "last_name": "Xian", "name": null }, { "creator_type": "author", "first_name": "Joseph", "last_name": "Lin", "name": null }, { "creator_type": "author", "first_name": "Jon M.", "last_name": "Fukuto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.freeradbiomed.2014.09.007" }, "pmcid": { "normalized": "PMC4258476" }, "pmid": { "normalized": "25229186" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Biosynthetic Pathways", "descriptor_ui": "D053898", "major_topic": false }, { "descriptor": "Cell Communication", "descriptor_ui": "D002450", "major_topic": false }, { "descriptor": "Disulfides", "descriptor_ui": "D004220", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Hydrogen Sulfide", "descriptor_ui": "D006862", "major_topic": false }, { "descriptor": "Oxidation-Reduction", "descriptor_ui": "D010084", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false } ], "publication": { "conference_name": null, "date": "2014 Dec", "date_precision": "unknown", "issue": "", "normalized_date": null, "pages": "82-94", "proceedings_title": null, "publisher": "", "title": "Free radical biology & medicine", "volume": "77", "year": 2014 }, "ssbd": { "database": [], "repository": [] }, "title": "Redox chemistry and chemical biology of H2S, hydropersulfides, and derived species: implications of their possible biological activity and utility.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Human induced pluripotent stem cell (hiPSC) lines have a great potential for therapeutics because customized cells and organs can be induced from such cells. Assessment of the residual reprogramming factors after the generation of hiPSC lines is required, but an ideal system has been lacking. Here, we generated hiPSC lines from normal human dermal fibroblasts with piggyBac transposon bearing reprogramming transgenes followed by removal of the transposon by the transposase. Under this condition, we compared the phenotypes of transgene-residual and -free hiPSCs of the same genetic background. The transgene-residual hiPSCs, in which the transcription levels of the reprogramming transgenes were eventually suppressed, were quite similar to the transgene-free hiPSCs in a pluripotent state. However, after differentiation into keratinocytes, clear differences were observed. Morphological, functional, and molecular analyses including single-cell gene expression profiling revealed that keratinocytes from transgene-free hiPSC lines were more similar to normal human keratinocytes than those from transgene-residual hiPSC lines, which may be partly explained by reactivation of residual transgenes upon induction of keratinocyte differentiation. These results suggest that transgene-free hiPSC lines should be chosen for therapeutic purposes.", "classifications": [ { "id": "Yusa", "label": "Group Yusa", "parent": "Eiraku", "type": "group" }, { "id": "Eiraku", "label": "Team Eiraku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Ken", "last_name": "Igawa", "name": null }, { "creator_type": "author", "first_name": "Chikara", "last_name": "Kokubu", "name": null }, { "creator_type": "author", "first_name": "Kosuke", "last_name": "Yusa", "name": null }, { "creator_type": "author", "first_name": "Kyoji", "last_name": "Horie", "name": null }, { "creator_type": "author", "first_name": "Yasuhide", "last_name": "Yoshimura", "name": null }, { "creator_type": "author", "first_name": "Kaori", "last_name": "Yamauchi", "name": null }, { "creator_type": "author", "first_name": "Hirofumi", "last_name": "Suemori", "name": null }, { "creator_type": "author", "first_name": "Hiroo", "last_name": "Yokozeki", "name": null }, { "creator_type": "author", "first_name": "Masashi", "last_name": "Toyoda", "name": null }, { "creator_type": "author", "first_name": "Nobutaka", "last_name": "Kiyokawa", "name": null }, { "creator_type": "author", "first_name": "Hajime", "last_name": "Okita", "name": null }, { "creator_type": "author", "first_name": "Yoshitaka", "last_name": "Miyagawa", "name": null }, { "creator_type": "author", "first_name": "Hidenori", "last_name": "Akutsu", "name": null }, { "creator_type": "author", "first_name": "Akihiro", "last_name": "Umezawa", "name": null }, { "creator_type": "author", "first_name": "Ichiro", "last_name": "Katayama", "name": null }, { "creator_type": "author", "first_name": "Junji", "last_name": "Takeda", "name": null } ], "identifiers": { "doi": { "normalized": "10.5966/sctm.2013-0179" }, "pmcid": { "normalized": "PMC4149296" }, "pmid": { "normalized": "25024429" } }, "mesh": [ { "descriptor": "Blotting, Southern", "descriptor_ui": "D015139", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Cellular Reprogramming", "descriptor_ui": "D065150", "major_topic": false }, { "descriptor": "Fibroblasts", "descriptor_ui": "D005347", "major_topic": false }, { "descriptor": "Genetic Engineering", "descriptor_ui": "D005818", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Immunohistochemistry", "descriptor_ui": "D007150", "major_topic": false }, { "descriptor": "Induced Pluripotent Stem Cells", "descriptor_ui": "D057026", "major_topic": false }, { "descriptor": "Keratinocytes", "descriptor_ui": "D015603", "major_topic": false }, { "descriptor": "Real-Time Polymerase Chain Reaction", "descriptor_ui": "D060888", "major_topic": false }, { "descriptor": "Tissue Engineering", "descriptor_ui": "D023822", "major_topic": false }, { "descriptor": "Transgenes", "descriptor_ui": "D019076", "major_topic": false } ], "publication": { "conference_name": null, "date": "2014 Sep", "date_precision": "unknown", "issue": "9", "normalized_date": null, "pages": "992-1001", "proceedings_title": null, "publisher": "", "title": "Stem cells translational medicine", "volume": "3", "year": 2014 }, "ssbd": { "database": [], "repository": [] }, "title": "Removal of reprogramming transgenes improves the tissue reconstitution potential of keratinocytes generated from human induced pluripotent stem cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Autophagy is a cellular self-catabolic process wherein organelles, macromolecules, and invading microbes are sequestered in autophagosomes that fuse with lysosomes. In this study, we uncover the role of nitric oxide (NO) as a signaling molecule for autophagy induction via its downstream mediator, 8-nitroguanosine 3',5'-cyclic monophosphate (8-nitro-cGMP). We found that 8-nitro-cGMP-induced autophagy is mediated by Lys63-linked polyubiquitination and that endogenous 8-nitro-cGMP promotes autophagic exclusion of invading group A Streptococcus (GAS) from cells. 8-nitro-cGMP can modify Cys residues by S-guanylation of proteins. We showed that intracellular GAS is modified with S-guanylation extensively in autophagosomes-like vacuoles, suggesting the role of S-guanylation as a marker for selective autophagic degradation. This finding is supported by the fact that S-guanylated bacteria were selectively marked with polyubiquitin, a known molecular tag for selective transport to autophagosomes. These results collectively indicate that 8-nitro-cGMP plays a crucial role in cytoprotection during bacterial infections or inflammations via autophagy upregulation.", "classifications": [ { "id": "Akaike", "label": "Group Akaike", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Chiaki", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Yohei", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Nozawa", "name": null }, { "creator_type": "author", "first_name": "Shigemoto", "last_name": "Fujii", "name": null }, { "creator_type": "author", "first_name": "Tomohiro", "last_name": "Sawa", "name": null }, { "creator_type": "author", "first_name": "Hirofumi", "last_name": "Inoue", "name": null }, { "creator_type": "author", "first_name": "Tetsuro", "last_name": "Matsunaga", "name": null }, { "creator_type": "author", "first_name": "Shahzada", "last_name": "Khan", "name": null }, { "creator_type": "author", "first_name": "Soichiro", "last_name": "Akashi", "name": null }, { "creator_type": "author", "first_name": "Ryota", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Chihiro", "last_name": "Aikawa", "name": null }, { "creator_type": "author", "first_name": "Eriko", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Sagara", "name": null }, { "creator_type": "author", "first_name": "Masaaki", "last_name": "Komatsu", "name": null }, { "creator_type": "author", "first_name": "Keiji", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Takaaki", "last_name": "Akaike", "name": null }, { "creator_type": "author", "first_name": "Ichiro", "last_name": "Nakagawa", "name": null }, { "creator_type": "author", "first_name": "Hirokazu", "last_name": "Arimoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.molcel.2013.10.024" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "24268578" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Autophagy", "descriptor_ui": "D001343", "major_topic": true }, { "descriptor": "Autophagy-Related Protein 5", "descriptor_ui": "D000071187", "major_topic": false }, { "descriptor": "Bacterial Proteins", "descriptor_ui": "D001426", "major_topic": false }, { "descriptor": "Cyclic GMP", "descriptor_ui": "D006152", "major_topic": false }, { "descriptor": "HeLa Cells", "descriptor_ui": "D006367", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Immunity, Innate", "descriptor_ui": "D007113", "major_topic": true }, { "descriptor": "Interferon-gamma", "descriptor_ui": "D007371", "major_topic": false }, { "descriptor": "Lipopolysaccharides", "descriptor_ui": "D008070", "major_topic": false }, { "descriptor": "Luminescent Proteins", "descriptor_ui": "D008164", "major_topic": false }, { "descriptor": "Macrophages", "descriptor_ui": "D008264", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Microtubule-Associated Proteins", "descriptor_ui": "D008869", "major_topic": false }, { "descriptor": "Nitric Oxide", "descriptor_ui": "D009569", "major_topic": false }, { "descriptor": "Polyubiquitin", "descriptor_ui": "D025821", "major_topic": false }, { "descriptor": "Protein Transport", "descriptor_ui": "D021381", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Streptococcus pyogenes", "descriptor_ui": "D013297", "major_topic": false }, { "descriptor": "Time Factors", "descriptor_ui": "D013997", "major_topic": false }, { "descriptor": "Transfection", "descriptor_ui": "D014162", "major_topic": false }, { "descriptor": "Ubiquitination", "descriptor_ui": "D054875", "major_topic": false } ], "publication": { "conference_name": null, "date": "2013 Dec 26", "date_precision": "day", "issue": "6", "normalized_date": "2013-12-26", "pages": "794-804", "proceedings_title": null, "publisher": "", "title": "Molecular cell", "volume": "52", "year": 2013 }, "ssbd": { "database": [], "repository": [] }, "title": "Endogenous nitrated nucleotide is a key mediator of autophagy and innate defense against bacteria.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Apoptotic cells are observed in the early developing brain. Apoptosis deficiency is proposed to cause brain overgrowth, but here we show that brain malformations in apoptosis-deficient mutants are due to insufficient brain ventricle expansion as a result of uncompleted cranial neural tube closure. Apoptosis eliminates Fgf8-expressing cells in the anterior neural ridge (ANR), which acts as an organizing center of the forebrain by producing FGF8 morphogen. Deficiency of apoptosis leads to the accumulation of undead and nonproliferative cells in the ventral part of the ANR. The undead cells in apoptosis-deficient mutants express Fgf8 continuously, which perturbs gene expression in the ventral forebrain. Thus, apoptosis within a specific subdomain of the ANR is required for correct temporal elimination of an FGF8-producing region within a limited developmental time window, thereby ensuring proper forebrain development.", "classifications": [ { "id": "Mochizuki", "label": "Group Mochizuki", "parent": "Eiraku", "type": "group" }, { "id": "Sawano", "label": "Group Sawano", "parent": "Shintaku", "type": "group" }, { "id": "Eiraku", "label": "Team Eiraku", "type": "team" }, { "id": "Shintaku", "label": "Team Shintaku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Keiko", "last_name": "Nonomura", "name": null }, { "creator_type": "author", "first_name": "Yoshifumi", "last_name": "Yamaguchi", "name": null }, { "creator_type": "author", "first_name": "Misato", "last_name": "Hamachi", "name": null }, { "creator_type": "author", "first_name": "Masato", "last_name": "Koike", "name": null }, { "creator_type": "author", "first_name": "Yasuo", "last_name": "Uchiyama", "name": null }, { "creator_type": "author", "first_name": "Kenichi", "last_name": "Nakazato", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Mochizuki", "name": null }, { "creator_type": "author", "first_name": "Asako", "last_name": "Sakaue-Sawano", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Miyawaki", "name": null }, { "creator_type": "author", "first_name": "Hiroki", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Keisuke", "last_name": "Kuida", "name": null }, { "creator_type": "author", "first_name": "Masayuki", "last_name": "Miura", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.devcel.2013.11.015" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "24369835" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Apoptosis", "descriptor_ui": "D017209", "major_topic": true }, { "descriptor": "Apoptotic Protease-Activating Factor 1", "descriptor_ui": "D053477", "major_topic": false }, { "descriptor": "Brain", "descriptor_ui": "D001921", "major_topic": false }, { "descriptor": "Cell Cycle", "descriptor_ui": "D002453", "major_topic": false }, { "descriptor": "Embryo, Mammalian", "descriptor_ui": "D004622", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Fibroblast Growth Factor 8", "descriptor_ui": "D051524", "major_topic": false }, { "descriptor": "Gene Expression Regulation, Developmental", "descriptor_ui": "D018507", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "In Situ Hybridization, Fluorescence", "descriptor_ui": "D017404", "major_topic": false }, { "descriptor": "Kinetics", "descriptor_ui": "D007700", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false } ], "publication": { "conference_name": null, "date": "2013 Dec 23", "date_precision": "day", "issue": "6", "normalized_date": "2013-12-23", "pages": "621-634", "proceedings_title": null, "publisher": "", "title": "Developmental cell", "volume": "27", "year": 2013 }, "ssbd": { "database": [], "repository": [] }, "title": "Local apoptosis modulates early mammalian brain development through the elimination of morphogen-producing cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Here, using further optimized 3D culture that allows highly selective induction and long-term growth of human ES cell (hESC)-derived cortical neuroepithelium, we demonstrate unique aspects of self-organization in human neocorticogenesis. Self-organized cortical tissue spontaneously forms a polarity along the dorsocaudal-ventrorostral axis and undergoes region-specific rolling morphogenesis that generates a semispherical structure. The neuroepithelium self-forms a multilayered structure including three neuronal zones (subplate, cortical plate, and Cajal-Retzius cell zones) and three progenitor zones (ventricular, subventricular, and intermediate zones) in the same apical-basal order as seen in the human fetal cortex in the early second trimester. In the cortical plate, late-born neurons tend to localize more basally to early-born neurons, consistent with the inside-out pattern seen in vivo. Furthermore, the outer subventricular zone contains basal progenitors that share characteristics with outer radial glia abundantly found in the human, but not mouse, fetal brain. Thus, human neocorticogenesis involves intrinsic programs that enable the emergence of complex neocortical features.", "classifications": [ { "id": "Eiraku", "label": "Group Eiraku", "parent": "Eiraku", "type": "group" }, { "id": "Eiraku", "label": "Team Eiraku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Taisuke", "last_name": "Kadoshima", "name": null }, { "creator_type": "author", "first_name": "Hideya", "last_name": "Sakaguchi", "name": null }, { "creator_type": "author", "first_name": "Tokushige", "last_name": "Nakano", "name": null }, { "creator_type": "author", "first_name": "Mika", "last_name": "Soen", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Ando", "name": null }, { "creator_type": "author", "first_name": "Mototsugu", "last_name": "Eiraku", "name": null }, { "creator_type": "author", "first_name": "Yoshiki", "last_name": "Sasai", "name": null } ], "identifiers": { "doi": { "normalized": "10.1073/pnas.1315710110" }, "pmcid": { "normalized": "PMC3864329" }, "pmid": { "normalized": "24277810" } }, "mesh": [ { "descriptor": "Amides", "descriptor_ui": "D000577", "major_topic": false }, { "descriptor": "Cell Culture Techniques", "descriptor_ui": "D018929", "major_topic": false }, { "descriptor": "Cell Polarity", "descriptor_ui": "D016764", "major_topic": false }, { "descriptor": "Collagen", "descriptor_ui": "D003094", "major_topic": false }, { "descriptor": "Drug Combinations", "descriptor_ui": "D004338", "major_topic": false }, { "descriptor": "Embryonic Stem Cells", "descriptor_ui": "D053595", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Laminin", "descriptor_ui": "D007797", "major_topic": false }, { "descriptor": "Neocortex", "descriptor_ui": "D019579", "major_topic": false }, { "descriptor": "Neuroglia", "descriptor_ui": "D009457", "major_topic": false }, { "descriptor": "Organogenesis", "descriptor_ui": "D038081", "major_topic": false }, { "descriptor": "Proteoglycans", "descriptor_ui": "D011509", "major_topic": false }, { "descriptor": "Pyridines", "descriptor_ui": "D011725", "major_topic": false }, { "descriptor": "Species Specificity", "descriptor_ui": "D013045", "major_topic": false } ], "publication": { "conference_name": null, "date": "2013 Dec 10", "date_precision": "day", "issue": "50", "normalized_date": "2013-12-10", "pages": "20284-20289", "proceedings_title": null, "publisher": "", "title": "Proceedings of the National Academy of Sciences of the United States of America", "volume": "110", "year": 2013 }, "ssbd": { "database": [], "repository": [] }, "title": "Self-organization of axial polarity, inside-out layer pattern, and species-specific progenitor dynamics in human ES cell-derived neocortex.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The basic helix-loop-helix transcription factors Ascl1/Mash1, Hes1, and Olig2 regulate fate choice of neurons, astrocytes, and oligodendrocytes, respectively. These same factors are coexpressed by neural progenitor cells. Here, we found by time-lapse imaging that these factors are expressed in an oscillatory manner by mouse neural progenitor cells. In each differentiation lineage, one of the factors becomes dominant. We used optogenetics to control expression of Ascl1 and found that, although sustained Ascl1 expression promotes neuronal fate determination, oscillatory Ascl1 expression maintains proliferating neural progenitor cells. Thus, the multipotent state correlates with oscillatory expression of several fate-determination factors, whereas the differentiated state correlates with sustained expression of a single factor.", "classifications": [ { "id": "Imayoshi", "label": "Group Imayoshi", "parent": "Imayoshi", "type": "group" }, { "id": "Imayoshi", "label": "Team Imayoshi", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Itaru", "last_name": "Imayoshi", "name": null }, { "creator_type": "author", "first_name": "Akihiro", "last_name": "Isomura", "name": null }, { "creator_type": "author", "first_name": "Yukiko", "last_name": "Harima", "name": null }, { "creator_type": "author", "first_name": "Kyogo", "last_name": "Kawaguchi", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Kori", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Miyachi", "name": null }, { "creator_type": "author", "first_name": "Takahiro", "last_name": "Fujiwara", "name": null }, { "creator_type": "author", "first_name": "Fumiyoshi", "last_name": "Ishidate", "name": null }, { "creator_type": "author", "first_name": "Ryoichiro", "last_name": "Kageyama", "name": null } ], "identifiers": { "doi": { "normalized": "10.1126/science.1242366" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "24179156" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Astrocytes", "descriptor_ui": "D001253", "major_topic": false }, { "descriptor": "Basic Helix-Loop-Helix Proteins", "descriptor_ui": "D051792", "major_topic": false }, { "descriptor": "Cell Lineage", "descriptor_ui": "D019070", "major_topic": false }, { "descriptor": "Cell Proliferation", "descriptor_ui": "D049109", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Gene Knock-In Techniques", "descriptor_ui": "D055879", "major_topic": false }, { "descriptor": "Homeodomain Proteins", "descriptor_ui": "D018398", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Transgenic", "descriptor_ui": "D008822", "major_topic": false }, { "descriptor": "Multipotent Stem Cells", "descriptor_ui": "D039902", "major_topic": false }, { "descriptor": "Nerve Tissue Proteins", "descriptor_ui": "D009419", "major_topic": false }, { "descriptor": "Neural Stem Cells", "descriptor_ui": "D058953", "major_topic": false }, { "descriptor": "Neurogenesis", "descriptor_ui": "D055495", "major_topic": true }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Oligodendrocyte Transcription Factor 2", "descriptor_ui": "D000076104", "major_topic": false }, { "descriptor": "Oligodendroglia", "descriptor_ui": "D009836", "major_topic": false }, { "descriptor": "Optogenetics", "descriptor_ui": "D062308", "major_topic": false }, { "descriptor": "Telencephalon", "descriptor_ui": "D013687", "major_topic": false }, { "descriptor": "Transcription Factor HES-1", "descriptor_ui": "D000072056", "major_topic": false }, { "descriptor": "Up-Regulation", "descriptor_ui": "D015854", "major_topic": false } ], "publication": { "conference_name": null, "date": "2013 Dec 6", "date_precision": "day", "issue": "6163", "normalized_date": "2013-12-06", "pages": "1203-1208", "proceedings_title": null, "publisher": "", "title": "Science (New York, N.Y.)", "volume": "342", "year": 2013 }, "ssbd": { "database": [], "repository": [] }, "title": "Oscillatory control of factors determining multipotency and fate in mouse neural progenitors.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The unsaturated ester aldehyde, (E)-3-alkoxycarbonyl-5-phenyl-2,4-dienal, was efficiently dimerized by applying the strain-promoted double-click reaction with sym-dibenzo-1,5-cyclooctadiene-3,7-diyne. The resulting dimerized probe was sequentially reacted first with one peptide molecule and then with a protein or the amino groups on the surface of a live cell through double azaelectrocyclization to achieve highly efficient bioconjugation.", "classifications": [ { "id": "Sodeoka", "label": "Group Sodeoka", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Katsunori", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Yuka", "last_name": "Nakamoto", "name": null }, { "creator_type": "author", "first_name": "Eric R. O.", "last_name": "Siwu", "name": null }, { "creator_type": "author", "first_name": "Ambara R.", "last_name": "Pradipta", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Morimoto", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Fujiwara", "name": null }, { "creator_type": "author", "first_name": "Suguru", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Takamitsu", "last_name": "Hosoya", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Tamura", "name": null }, { "creator_type": "author", "first_name": "Go", "last_name": "Hirai", "name": null }, { "creator_type": "author", "first_name": "Mikiko", "last_name": "Sodeoka", "name": null }, { "creator_type": "author", "first_name": "Koichi", "last_name": "Fukase", "name": null } ], "identifiers": { "doi": { "normalized": "10.1039/c3ob41507d" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "24068279" } }, "mesh": [ { "descriptor": "Aldehydes", "descriptor_ui": "D000447", "major_topic": false }, { "descriptor": "Alkynes", "descriptor_ui": "D000480", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Survival", "descriptor_ui": "D002470", "major_topic": false }, { "descriptor": "Cyclization", "descriptor_ui": "D003500", "major_topic": false }, { "descriptor": "Dimerization", "descriptor_ui": "D019281", "major_topic": false }, { "descriptor": "Esters", "descriptor_ui": "D004952", "major_topic": false }, { "descriptor": "HeLa Cells", "descriptor_ui": "D006367", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Peptides", "descriptor_ui": "D010455", "major_topic": false }, { "descriptor": "Serum Albumin", "descriptor_ui": "D012709", "major_topic": false } ], "publication": { "conference_name": null, "date": "2013 Nov 14", "date_precision": "day", "issue": "42", "normalized_date": "2013-11-14", "pages": "7326-7333", "proceedings_title": null, "publisher": "", "title": "Organic & biomolecular chemistry", "volume": "11", "year": 2013 }, "ssbd": { "database": [], "repository": [] }, "title": "Development of bis-unsaturated ester aldehydes as amino-glue probes: sequential double azaelectrocyclization as a promising strategy for bioconjugation.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Sox2 is a transcription factor required for the maintenance of pluripotency. It also plays an essential role in different types of multipotent stem cells, raising the possibility that Sox2 governs the common stemness phenotype. Here we show that Sox2 is a critical downstream target of fibroblast growth factor (FGF) signaling, which mediates self-renewal of trophoblast stem cells (TSCs). Sustained expression of Sox2 together with Esrrb or Tfap2c can replace FGF dependency. By comparing genome-wide binding sites of Sox2 in embryonic stem cells (ESCs) and TSCs combined with inducible knockout systems, we found that, despite the common role in safeguarding the stem cell state, Sox2 regulates distinct sets of genes with unique functions in these two different yet developmentally related types of stem cells. Our findings provide insights into the functional versatility of transcription factors during embryogenesis, during which they can be recursively utilized in a variable manner within discrete network structures.", "classifications": [ { "id": "Nikaido", "label": "Group Nikaido", "parent": "Fujiwara", "type": "group" }, { "id": "Fujiwara", "label": "Team Fujiwara", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Kenjiro", "last_name": "Adachi", "name": null }, { "creator_type": "author", "first_name": "Itoshi", "last_name": "Nikaido", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Ohta", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Ohtsuka", "name": null }, { "creator_type": "author", "first_name": "Hiroki", "last_name": "Ura", "name": null }, { "creator_type": "author", "first_name": "Mitsutaka", "last_name": "Kadota", "name": null }, { "creator_type": "author", "first_name": "Teruhiko", "last_name": "Wakayama", "name": null }, { "creator_type": "author", "first_name": "Hiroki R.", "last_name": "Ueda", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Niwa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.molcel.2013.09.002" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "24120664" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "Embryonic Development", "descriptor_ui": "D047108", "major_topic": false }, { "descriptor": "Embryonic Stem Cells", "descriptor_ui": "D053595", "major_topic": false }, { "descriptor": "Fibroblast Growth Factors", "descriptor_ui": "D005346", "major_topic": false }, { "descriptor": "Gene Expression Regulation, Developmental", "descriptor_ui": "D018507", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Pluripotent Stem Cells", "descriptor_ui": "D039904", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "SOXB1 Transcription Factors", "descriptor_ui": "D055748", "major_topic": false }, { "descriptor": "Stem Cells", "descriptor_ui": "D013234", "major_topic": false }, { "descriptor": "Transcription Factor AP-2", "descriptor_ui": "D050656", "major_topic": false }, { "descriptor": "Trophoblasts", "descriptor_ui": "D014327", "major_topic": false } ], "publication": { "conference_name": null, "date": "2013 Nov 7", "date_precision": "day", "issue": "3", "normalized_date": "2013-11-07", "pages": "380-392", "proceedings_title": null, "publisher": "", "title": "Molecular cell", "volume": "52", "year": 2013 }, "ssbd": { "database": [], "repository": [] }, "title": "Context-dependent wiring of Sox2 regulatory networks for self-renewal of embryonic and trophoblast stem cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Melanocortin-4 receptor (MC4R)-expressing neurons are widely distributed in the central nervous system and play a crucial role in a variety of physiological functions including energy and glucose/insulin homeostasis. However, their neural pathways remain to be elucidated. In the present study, we examined a possible pathway from MC4R-expressing neurons in the dorsal motor nucleus of the vagus nerve (DMV) to the intrapancreatic ganglia using transgenic mice that express green fluorescent protein (GFP) under the control of the MC4R-promoter. Using immunofluorescence labeling, we demonstrated that GFP-immunoreactive (ir) nerve fibers were distributed in the intrapancreatic ganglia closely associated with the islets as well as among the acini. These GFP-ir fibers with bouton-like varicosities were frequently observed to surround ganglion cells immunoreactive for vasoactive intestinal polypeptide, a marker for postganglionic parasympathetic neurons. Using the pre-embedding immunoperoxidase method, we clearly showed that GFP-ir terminals formed synapses predominantly with dendrites and additionally with somata of the ganglion cells. Moreover, bilateral subdiaphragmatic vagotomy caused a marked loss of GFP immunoreactivity in the pancreas. Using a combination of retrograde tracing and immunohistochemistry, we finally demonstrated that nearly half of the pancreas-projecting DMV neurons were immunoreactive for GFP. These results suggest that MC4R-expressing DMV neurons may participate in the regulation of glucose/insulin homeostasis through their projections to the intrapancreatic ganglia.", "classifications": [ { "id": "Yokota", "label": "Group Yokota", "parent": "Enomoto", "type": "group" }, { "id": "Enomoto", "label": "Team Enomoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Toshiko", "last_name": "Tsumori", "name": null }, { "creator_type": "author", "first_name": "Tatsuro", "last_name": "Oka", "name": null }, { "creator_type": "author", "first_name": "Shigefumi", "last_name": "Yokota", "name": null }, { "creator_type": "author", "first_name": "Jian-Guo", "last_name": "Niu", "name": null }, { "creator_type": "author", "first_name": "Yukihiko", "last_name": "Yasui", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.brainres.2013.09.002" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "24028856" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Ganglia, Parasympathetic", "descriptor_ui": "D005726", "major_topic": false }, { "descriptor": "Immunohistochemistry", "descriptor_ui": "D007150", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Transgenic", "descriptor_ui": "D008822", "major_topic": false }, { "descriptor": "Nerve Fibers", "descriptor_ui": "D009412", "major_topic": false }, { "descriptor": "Neural Pathways", "descriptor_ui": "D009434", "major_topic": false }, { "descriptor": "Nodose Ganglion", "descriptor_ui": "D009620", "major_topic": false }, { "descriptor": "Receptor, Melanocortin, Type 4", "descriptor_ui": "D044105", "major_topic": false }, { "descriptor": "Synapses", "descriptor_ui": "D013569", "major_topic": false }, { "descriptor": "Vagus Nerve", "descriptor_ui": "D014630", "major_topic": false } ], "publication": { "conference_name": null, "date": "2013 Nov 6", "date_precision": "day", "issue": "", "normalized_date": "2013-11-06", "pages": "132-142", "proceedings_title": null, "publisher": "", "title": "Brain research", "volume": "1537", "year": 2013 }, "ssbd": { "database": [], "repository": [] }, "title": "Intrapancreatic ganglia neurons receive projection fibers from melanocortin-4 receptor-expressing neurons in the dorsal motor nucleus of the vagus nerve of the mouse.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Alternative splicing generates multiple transcripts from a single gene, and cell-type-specific splicing profiles are important for the properties and functions of the cells. Recently, somatic cells have been shown to undergo dedifferentiation after the forced expression of transcription factors. However, it remains unclear whether somatic cell splicing is reorganized during reprogramming. Here, by combining deep sequencing with high-throughput absolute qRT-PCR, we show that somatic splicing profiles revert to pluripotent ones during reprogramming. Remarkably, the splicing pattern in pluripotent stem cells resembles that in testes, and the regulatory regions have specific characteristics in length and sequence. Furthermore, our siRNA screen has identified RNA-binding proteins that regulate splicing events in iPSCs. We have then demonstrated that two of the RNA-binding proteins, U2af1 and Srsf3, play a role in somatic cell reprogramming. Our results indicate that the drastic alteration in splicing represents part of the molecular network involved in the reprogramming process.", "classifications": [ { "id": "Yamamoto", "label": "Group Yamamoto", "parent": "Toyoshima", "type": "group" }, { "id": "Toyoshima", "label": "Team Toyoshima", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Sho", "last_name": "Ohta", "name": null }, { "creator_type": "author", "first_name": "Eisuke", "last_name": "Nishida", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Yamanaka", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Yamamoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.celrep.2013.09.016" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "24139801" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "Cellular Reprogramming", "descriptor_ui": "D065150", "major_topic": true }, { "descriptor": "Exons", "descriptor_ui": "D005091", "major_topic": false }, { "descriptor": "Gene Expression Regulation", "descriptor_ui": "D005786", "major_topic": false }, { "descriptor": "Induced Pluripotent Stem Cells", "descriptor_ui": "D057026", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Nuclear Proteins", "descriptor_ui": "D009687", "major_topic": false }, { "descriptor": "Ribonucleoproteins", "descriptor_ui": "D012261", "major_topic": false }, { "descriptor": "RNA Interference", "descriptor_ui": "D034622", "major_topic": false }, { "descriptor": "RNA Splicing", "descriptor_ui": "D012326", "major_topic": true }, { "descriptor": "RNA, Messenger", "descriptor_ui": "D012333", "major_topic": false }, { "descriptor": "RNA, Small Interfering", "descriptor_ui": "D034741", "major_topic": false }, { "descriptor": "RNA-Binding Proteins", "descriptor_ui": "D016601", "major_topic": false }, { "descriptor": "Serine-Arginine Splicing Factors", "descriptor_ui": "D000068103", "major_topic": false }, { "descriptor": "Splicing Factor U2AF", "descriptor_ui": "D000072668", "major_topic": false } ], "publication": { "conference_name": null, "date": "2013 Oct 31", "date_precision": "day", "issue": "2", "normalized_date": "2013-10-31", "pages": "357-366", "proceedings_title": null, "publisher": "", "title": "Cell reports", "volume": "5", "year": 2013 }, "ssbd": { "database": [], "repository": [] }, "title": "Global splicing pattern reversion during somatic cell reprogramming.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Modern biology provides many networks describing regulations between many species of molecules. It is widely believed that the dynamics of molecular activities based on such regulatory networks are the origin of biological functions. However, we currently have a limited understanding of the relationship between the structure of a regulatory network and its dynamics. In this study we develop a new theory to provide an important aspect of dynamics from information of regulatory linkages alone. We show that the \"feedback vertex set\" (FVS) of a regulatory network is a set of \"determining nodes\" of the dynamics. The theory is powerful to study real biological systems in practice. It assures that (i) any long-term dynamical behavior of the whole system, such as steady states, periodic oscillations or quasi-periodic oscillations, can be identified by measurements of a subset of molecules in the network, and that (ii) the subset is determined from the regulatory linkage alone. For example, dynamical attractors possibly generated by a signal transduction network with 113 molecules can be identified by measurement of the activity of only 5 molecules, if the information on the network structure is correct. Our theory therefore provides a rational criterion to select key molecules to control a system. We also demonstrate that controlling the dynamics of the FVS is sufficient to switch the dynamics of the whole system from one attractor to others, distinct from the original.", "classifications": [ { "id": "Mochizuki", "label": "Group Mochizuki", "parent": "Eiraku", "type": "group" }, { "id": "Eiraku", "label": "Team Eiraku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Atsushi", "last_name": "Mochizuki", "name": null }, { "creator_type": "author", "first_name": "Bernold", "last_name": "Fiedler", "name": null }, { "creator_type": "author", "first_name": "Gen", "last_name": "Kurosawa", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Saito", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.jtbi.2013.06.009" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "23774067" } }, "mesh": [ { "descriptor": "Models, Biological", "descriptor_ui": "D008954", "major_topic": true }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false } ], "publication": { "conference_name": null, "date": "2013 Oct 21", "date_precision": "day", "issue": "", "normalized_date": "2013-10-21", "pages": "130-146", "proceedings_title": null, "publisher": "", "title": "Journal of theoretical biology", "volume": "335", "year": 2013 }, "ssbd": { "database": [], "repository": [] }, "title": "Dynamics and control at feedback vertex sets. II: a faithful monitor to determine the diversity of molecular activities in regulatory networks.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Migratory cells, including mammalian leukocytes and Dictyostelium, use G-protein-coupled receptor (GPCR) signaling to regulate MAPK/ERK, PI3K, TORC2/AKT, adenylyl cyclase and actin polymerization, which collectively direct chemotaxis. Upon ligand binding, mammalian GPCRs are phosphorylated at cytoplasmic residues, uncoupling G-protein pathways, but activating other pathways. However, connections between GPCR phosphorylation and chemotaxis are unclear. In developing Dictyostelium, secreted cAMP serves as a chemoattractant, with extracellular cAMP propagated as oscillating waves to ensure directional migratory signals. cAMP oscillations derive from transient excitatory responses of adenylyl cyclase, which then rapidly adapts. We have studied chemotactic signaling in Dictyostelium that express non-phosphorylatable cAMP receptors and show through chemotaxis modeling, single-cell FRET imaging, pure and chimeric population wavelet quantification, biochemical analyses and TIRF microscopy, that receptor phosphorylation is required to regulate adenylyl cyclase adaptation, long-range oscillatory cAMP wave production and cytoskeletal actin response. Phosphorylation defects thus promote hyperactive actin polymerization at the cell periphery, misdirected pseudopodia and the loss of directional chemotaxis. Our data indicate that chemoattractant receptor phosphorylation is required to co-regulate essential pathways for migratory cell polarization and chemotaxis. Our results significantly extend the understanding of the function of GPCR phosphorylation, providing strong evidence that this evolutionarily conserved mechanism is required in a signal attenuation pathway that is necessary to maintain persistent directional movement of Dictyostelium, neutrophils and other migratory cells.", "classifications": [ { "id": "Sawai", "label": "Group Sawai", "parent": "Sawai", "type": "group" }, { "id": "Sawai", "label": "Team Sawai", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Joseph A.", "last_name": "Brzostowski", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Sawai", "name": null }, { "creator_type": "author", "first_name": "Orr", "last_name": "Rozov", "name": null }, { "creator_type": "author", "first_name": "Xin-hua", "last_name": "Liao", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Imoto", "name": null }, { "creator_type": "author", "first_name": "Carole A.", "last_name": "Parent", "name": null }, { "creator_type": "author", "first_name": "Alan R.", "last_name": "Kimmel", "name": null } ], "identifiers": { "doi": { "normalized": "10.1242/jcs.122952" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "23902692" } }, "mesh": [ { "descriptor": "Actins", "descriptor_ui": "D000199", "major_topic": false }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Chemotaxis", "descriptor_ui": "D002633", "major_topic": false }, { "descriptor": "Dictyostelium", "descriptor_ui": "D004023", "major_topic": false }, { "descriptor": "Mechanistic Target of Rapamycin Complex 2", "descriptor_ui": "D000076225", "major_topic": false }, { "descriptor": "Microscopy, Confocal", "descriptor_ui": "D018613", "major_topic": false }, { "descriptor": "Mitogen-Activated Protein Kinase 1", "descriptor_ui": "D019950", "major_topic": false }, { "descriptor": "Multiprotein Complexes", "descriptor_ui": "D046912", "major_topic": false }, { "descriptor": "Phosphatidylinositol 3-Kinases", "descriptor_ui": "D019869", "major_topic": false }, { "descriptor": "Phosphorylation", "descriptor_ui": "D010766", "major_topic": false }, { "descriptor": "Protozoan Proteins", "descriptor_ui": "D015800", "major_topic": false }, { "descriptor": "Receptors, Cyclic AMP", "descriptor_ui": "D011953", "major_topic": false }, { "descriptor": "Receptors, G-Protein-Coupled", "descriptor_ui": "D043562", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "TOR Serine-Threonine Kinases", "descriptor_ui": "D058570", "major_topic": false } ], "publication": { "conference_name": null, "date": "2013 Oct 15", "date_precision": "day", "issue": "20", "normalized_date": "2013-10-15", "pages": "4614-4626", "proceedings_title": null, "publisher": "", "title": "Journal of Cell Science", "volume": "126", "year": 2013 }, "ssbd": { "database": [], "repository": [] }, "title": "Phosphorylation of chemoattractant receptors regulates chemotaxis, actin reorganization and signal relay.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Neurite growth requires two guanine nucleotide-binding protein polymers of tubulins and septins. However, whether and how those cytoskeletal systems are coordinated was unknown. Here we show that the acute knockdown or knockout of the pivotal septin subunit SEPT7 from cerebrocortical neurons impairs their interhemispheric and cerebrospinal axon projections and dendritogenesis in perinatal mice, when the microtubules are severely hyperacetylated. The resulting hyperstabilization and growth retardation of microtubules are demonstrated in vitro. The phenotypic similarity between SEPT7 depletion and the pharmacological inhibition of α-tubulin deacetylase HDAC6 reveals that HDAC6 requires SEPT7 not for its enzymatic activity, but to associate with acetylated α-tubulin. These and other findings indicate that septins provide a physical scaffold for HDAC6 to achieve efficient microtubule deacetylation, thereby negatively regulating microtubule stability to an optimal level for neuritogenesis. Our findings shed light on the mechanisms underlying the HDAC6-mediated coupling of the two ubiquitous cytoskeletal systems during neural development.", "classifications": [ { "id": "Sato", "label": "Group Sato", "parent": "Tsuchiya", "type": "group" }, { "id": "Tsuchiya", "label": "Team Tsuchiya", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Natsumi", "last_name": "Ageta-Ishihara", "name": null }, { "creator_type": "author", "first_name": "Takaki", "last_name": "Miyata", "name": null }, { "creator_type": "author", "first_name": "Chika", "last_name": "Ohshima", "name": null }, { "creator_type": "author", "first_name": "Masahiko", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Yoshikatsu", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Hamamura", "name": null }, { "creator_type": "author", "first_name": "Tetsuya", "last_name": "Higashiyama", "name": null }, { "creator_type": "author", "first_name": "Ralph", "last_name": "Mazitschek", "name": null }, { "creator_type": "author", "first_name": "Haruhiko", "last_name": "Bito", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Kinoshita", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/ncomms3532" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "24113571" } }, "mesh": [ { "descriptor": "Acetylation", "descriptor_ui": "D000107", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Animals, Newborn", "descriptor_ui": "D000831", "major_topic": false }, { "descriptor": "Axons", "descriptor_ui": "D001369", "major_topic": false }, { "descriptor": "Cerebral Cortex", "descriptor_ui": "D002540", "major_topic": false }, { "descriptor": "Dendrites", "descriptor_ui": "D003712", "major_topic": false }, { "descriptor": "Fetus", "descriptor_ui": "D005333", "major_topic": false }, { "descriptor": "Gene Expression Regulation, Developmental", "descriptor_ui": "D018507", "major_topic": false }, { "descriptor": "Gene Knockdown Techniques", "descriptor_ui": "D055785", "major_topic": false }, { "descriptor": "Gene Knockout Techniques", "descriptor_ui": "D055786", "major_topic": false }, { "descriptor": "Histone Deacetylase 6", "descriptor_ui": "D000073864", "major_topic": false }, { "descriptor": "Histone Deacetylases", "descriptor_ui": "D006655", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Microtubules", "descriptor_ui": "D008870", "major_topic": false }, { "descriptor": "Neurogenesis", "descriptor_ui": "D055495", "major_topic": false }, { "descriptor": "Septins", "descriptor_ui": "D058112", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Tubulin", "descriptor_ui": "D014404", "major_topic": false } ], "publication": { "conference_name": null, "date": "2013-10-11", "date_precision": "day", "issue": "", "normalized_date": "2013-10-11", "pages": "", "proceedings_title": null, "publisher": "", "title": "Nature Communications", "volume": "4", "year": 2013 }, "ssbd": { "database": [], "repository": [] }, "title": "Septins promote dendrite and axon development by negatively regulating microtubule stability via HDAC6-mediated deacetylation.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Pleiotropic growth factors play a number of critical roles in continuous processes of embryonic development; however, the mechanisms by which a single regulatory factor is able to orchestrate diverse developmental events remain imperfectly understood. In the development of the enteric nervous system (ENS), myenteric ganglia (MGs) form initially, after which the submucosal ganglia (SMGs) develop by radial inward migration of immature ENS precursors from the myenteric layer. Here, we demonstrate that glial cell line-derived neurotrophic factor (GDNF) is essential for the formation not only of the MGs, but the SMGs as well, establishing GDNF as a long-term acting neurotrophic factor for ENS development in a mouse model. GDNF promotes radial migration of SMG precursors. Interestingly, premigratory SMG precursors in the myenteric layer were distinguished from the surrounding neuronally differentiating cells by their lower activation of the GDNF-mediated MAPK pathway, suggesting that low activation of GDNF downstream pathways is required for the maintenance of the immature state. ENS precursors devoid of GDNF signaling during midgestation halt their migration, survive, and remain in an undifferentiated state over the long-term in vivo. Reactivation of GDNF signaling in these dormant precursors restores their migration and neuronal differentiation in gut organ culture. These findings suggest that pleiotropic function of GDNF is at least in part governed by modulating levels of intracellular activation of GDNF downstream pathways; high activation triggers neuronal differentiation, whereas low activation is crucial for the maintenance of progenitor state.", "classifications": [ { "id": "Enomoto", "label": "Group Enomoto", "parent": "Enomoto", "type": "group" }, { "id": "Enomoto", "label": "Team Enomoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Toshihiro", "last_name": "Uesaka", "name": null }, { "creator_type": "author", "first_name": "Mayumi", "last_name": "Nagashimada", "name": null }, { "creator_type": "author", "first_name": "Hideki", "last_name": "Enomoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1523/jneurosci.2079-13.2013" }, "pmcid": { "normalized": "PMC6618356" }, "pmid": { "normalized": "24107967" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Cell Movement", "descriptor_ui": "D002465", "major_topic": true }, { "descriptor": "Enteric Nervous System", "descriptor_ui": "D017615", "major_topic": false }, { "descriptor": "Glial Cell Line-Derived Neurotrophic Factor", "descriptor_ui": "D051100", "major_topic": false }, { "descriptor": "Immunohistochemistry", "descriptor_ui": "D007150", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Mutant Strains", "descriptor_ui": "D008817", "major_topic": false }, { "descriptor": "Neural Stem Cells", "descriptor_ui": "D058953", "major_topic": false }, { "descriptor": "Neurogenesis", "descriptor_ui": "D055495", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false } ], "publication": { "conference_name": null, "date": "2013 Oct 9", "date_precision": "day", "issue": "41", "normalized_date": "2013-10-09", "pages": "16372-16382", "proceedings_title": null, "publisher": "", "title": "The Journal of neuroscience : the official journal of the Society for Neuroscience", "volume": "33", "year": 2013 }, "ssbd": { "database": [], "repository": [] }, "title": "GDNF signaling levels control migration and neuronal differentiation of enteric ganglion precursors.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "We report, for the first time, the saturated excitation (SAX) of fluorescent proteins for subdiffraction-limited imaging of living cells in three-dimensions. To achieve saturation, a bright yellow and green fluorescent protein (Venus and EGFP) that exhibits a strong nonlinear fluorescence response to the high excitation intensity at the laser focus is used. Harmonic demodulation of the fluorescence signal produced by a modulated excitation light extracts the nonlinear fluorescence signals. After constructing the image from the nonlinear components, we obtain fluorescence images of living cells with spatial resolution beyond the diffraction limit. We also applied linear deconvolution to SAX microscopy and found it effective in further enhancing the contrast of small intracellular structures in the SAX image, confirming the expansion of the optical transfer function in SAX microscopy.", "classifications": [ { "id": "Fujita", "label": "Group Fujita", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Masahito", "last_name": "Yamanaka", "name": null }, { "creator_type": "author", "first_name": "Kenta", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Nicholas I.", "last_name": "Smith", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Kawata", "name": null }, { "creator_type": "author", "first_name": "Takeharu", "last_name": "Nagai", "name": null }, { "creator_type": "author", "first_name": "Katsumasa", "last_name": "Fujita", "name": null } ], "identifiers": { "doi": { "normalized": "10.1098/rsfs.2013.0007" }, "pmcid": { "normalized": "PMC3915824" }, "pmid": { "normalized": "24511385" } }, "mesh": [], "publication": { "conference_name": null, "date": "2013 Oct 6", "date_precision": "day", "issue": "5", "normalized_date": "2013-10-06", "pages": "20130007", "proceedings_title": null, "publisher": "", "title": "Interface focus", "volume": "3", "year": 2013 }, "ssbd": { "database": [], "repository": [] }, "title": "Saturated excitation of fluorescent proteins for subdiffraction-limited imaging of living cells in three dimensions.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: For the analysis of spatio-temporal dynamics, various automated processing methods have been developed for nuclei segmentation. These methods tend to be complex for segmentation of images with crowded nuclei, preventing the simple reapplication of the methods to other problems. Thus, it is useful to evaluate the ability of simple methods to segment images with various degrees of crowded nuclei. RESULTS: Here, we selected six simple methods from various watershed based and local maxima detection based methods that are frequently used for nuclei segmentation, and evaluated their segmentation accuracy for each developmental stage of the Caenorhabditis elegans. We included a 4D noise filter, in addition to 2D and 3D noise filters, as a pre-processing step to evaluate the potential of simple methods as widely as possible. By applying the methods to image data between the 50- to 500-cell developmental stages at 50-cell intervals, the error rate for nuclei detection could be reduced to 0.100 in Japanese populations. The estimated glomerular filtration rate (eGFR) and CKD prevalence (eGFR < 60 ml/min/1.73 m2) of the subjects were compared among the genotypes. Results: A higher eGFR and lower prevalence of CKD were observed for the homozygous variants of IL4 -33CC (high IL-4 [anti-inflammatory cytokine]-producing genotype) and IL6 -572GG (low IL-6 [pro-inflammatory cytokine]-producing genotype). Subjects with IL4 CC + IL6 GG showed the highest mean eGFR (79.1 ml/min/1.73 m2) and lowest CKD prevalence (0.0%), while subjects carrying IL4 TT + IL6 CC showed the lowest mean eGFR (73.4 ml/min/1.73 m2) and highest CKD prevalence (17.9%). Conclusions: The functional promoter polymorphisms IL4 T-33C (rs2070874) and IL6 C-572G (rs1800796), which are the only SNPs that affect the IL-4 and IL-6 levels in Japanese subjects, were associated with kidney function and CKD prevalence in a large Japanese population.", "classifications": [ { "id": "Tanaka", "label": "Group Tanaka", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Rieko", "last_name": "Okada", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Wakai", "name": null }, { "creator_type": "author", "first_name": "Mariko", "last_name": "Naito", "name": null }, { "creator_type": "author", "first_name": "Emi", "last_name": "Morita", "name": null }, { "creator_type": "author", "first_name": "Sayo", "last_name": "Kawai", "name": null }, { "creator_type": "author", "first_name": "Nobuyuki", "last_name": "Hamajima", "name": null }, { "creator_type": "author", "first_name": "Megumi", "last_name": "Hara", "name": null }, { "creator_type": "author", "first_name": "Naoyuki", "last_name": "Takashima", "name": null }, { "creator_type": "author", "first_name": "Sadao", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Toshiro", "last_name": "Takezaki", "name": null }, { "creator_type": "author", "first_name": "Keizo", "last_name": "Ohnaka", "name": null }, { "creator_type": "author", "first_name": "Kokichi", "last_name": "Arisawa", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Hirohata", "name": null }, { "creator_type": "author", "first_name": "Keitaro", "last_name": "Matsuo", "name": null }, { "creator_type": "author", "first_name": "Haruo", "last_name": "Mikami", "name": null }, { "creator_type": "author", "first_name": "Michiaki", "last_name": "Kubo", "name": null }, { "creator_type": "author", "first_name": "Hideo", "last_name": "Tanaka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1186/1471-2369-13-2" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "22230215" } }, "mesh": [ { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Asian People", "descriptor_ui": "D044466", "major_topic": false }, { "descriptor": "Cross-Sectional Studies", "descriptor_ui": "D003430", "major_topic": false }, { "descriptor": "Cytokines", "descriptor_ui": "D016207", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Genotype", "descriptor_ui": "D005838", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Inflammation", "descriptor_ui": "D007249", "major_topic": false }, { "descriptor": "Kidney Failure, Chronic", "descriptor_ui": "D007676", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Polymorphism, Single Nucleotide", "descriptor_ui": "D020641", "major_topic": true }, { "descriptor": "Promoter Regions, Genetic", "descriptor_ui": "D011401", "major_topic": false } ], "publication": { "conference_name": null, "date": "2012", "date_precision": "year", "issue": "", "normalized_date": "2012", "pages": "2", "proceedings_title": null, "publisher": "", "title": "BMC Nephrology", "volume": "13", "year": 2012 }, "ssbd": { "database": [], "repository": [] }, "title": "Pro-/anti-inflammatory cytokine gene polymorphisms and chronic kidney disease: a cross-sectional study.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Background: Depletion of replication factors often causes cell death in cancer cells. Depletion of Cdc7, a kinase essential for initiation of DNA replication, induces cancer cell death regardless of its p53 status, but the precise pathways of cell death induction have not been characterized. Methodology/Principal Findings: We have used the recently-developed cell cycle indicator, Fucci, to precisely characterize the cell death process induced by Cdc7 depletion. We have also generated and utilized similar fluorescent cell cycle indicators using fusion with other cell cycle regulators to analyze modes of cell death in live cells in both p53-positive and -negative backgrounds. We show that distinct cell-cycle responses are induced in p53-positive and -negative cells by Cdc7 depletion. p53-negative cells predominantly arrest temporally in G2-phase, accumulating CyclinB1 and other mitotic regulators. Prolonged arrest at G2-phase and abrupt entry into aberrant M-phase in the presence of accumulated CyclinB1 are followed by cell death at the post-mitotic state. Abrogation of cytoplasmic CyclinB1 accumulation partially decreases cell death. The ATR-MK2 pathway is responsible for sequestration of CyclinB1 with 14-3-3σ protein. In contrast, p53-positive cancer cells do not accumulate CyclinB1, but appear to die mostly through entry into aberrant S-phase after Cdc7 depletion. The combination of Cdc7 inhibition with known anti-cancer agents significantly stimulates cell death effects in cancer cells in a genotype-dependent manner, providing a strategic basis for future combination therapies. Conclusions: Our results show that the use of Fucci, and similar fluorescent cell cycle indicators, offers a convenient assay system with which to identify cell cycle events associated with cancer cell death. They also indicate genotype-specific cell death modes induced by deficient initiation of DNA replication in cancer cells and its potential exploitation for development of efficient cancer therapies.", "classifications": [ { "id": "Sawano", "label": "Group Sawano", "parent": "Shintaku", "type": "group" }, { "id": "Shintaku", "label": "Team Shintaku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Sayuri", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Ai", "last_name": "Ishii", "name": null }, { "creator_type": "author", "first_name": "Naoko", "last_name": "Kakusho", "name": null }, { "creator_type": "author", "first_name": "Chika", "last_name": "Taniyama", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Yamazaki", "name": null }, { "creator_type": "author", "first_name": "Rino", "last_name": "Fukatsu", "name": null }, { "creator_type": "author", "first_name": "Asako", "last_name": "Sakaue-Sawano", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Miyawaki", "name": null }, { "creator_type": "author", "first_name": "Hisao", "last_name": "Masai", "name": null } ], "identifiers": { "doi": { "normalized": "10.1371/journal.pone.0036372" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "22574151" } }, "mesh": [ { "descriptor": "14-3-3 Proteins", "descriptor_ui": "D048948", "major_topic": false }, { "descriptor": "Antineoplastic Agents", "descriptor_ui": "D000970", "major_topic": false }, { "descriptor": "Biomarkers, Tumor", "descriptor_ui": "D014408", "major_topic": false }, { "descriptor": "Cell Cycle Proteins", "descriptor_ui": "D018797", "major_topic": false }, { "descriptor": "Cell Death", "descriptor_ui": "D016923", "major_topic": false }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Cyclin B1", "descriptor_ui": "D056744", "major_topic": false }, { "descriptor": "Cytoplasm", "descriptor_ui": "D003593", "major_topic": false }, { "descriptor": "DNA Replication", "descriptor_ui": "D004261", "major_topic": true }, { "descriptor": "Enzyme Activation", "descriptor_ui": "D004789", "major_topic": false }, { "descriptor": "Exonucleases", "descriptor_ui": "D005092", "major_topic": false }, { "descriptor": "Exoribonucleases", "descriptor_ui": "D005095", "major_topic": false }, { "descriptor": "G2 Phase", "descriptor_ui": "D016195", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Intracellular Signaling Peptides and Proteins", "descriptor_ui": "D047908", "major_topic": false }, { "descriptor": "MAP-Kinase-Activated Kinase 2", "descriptor_ui": "D000099190", "major_topic": false }, { "descriptor": "Protein Serine-Threonine Kinases", "descriptor_ui": "D017346", "major_topic": false }, { "descriptor": "RNA, Small Interfering", "descriptor_ui": "D034741", "major_topic": false }, { "descriptor": "Tumor Suppressor Protein p53", "descriptor_ui": "D016159", "major_topic": false } ], "publication": { "conference_name": null, "date": "2012", "date_precision": "year", "issue": "5", "normalized_date": "2012", "pages": "", "proceedings_title": null, "publisher": "", "title": "PLoS ONE", "volume": "7", "year": 2012 }, "ssbd": { "database": [], "repository": [] }, "title": "Mechanism of Cancer Cell Death Induced by Depletion of an Essential Replication Regulator.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Bronchiolitis obliterans (BO) is one of the serious, noninfectious pulmonary complications after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Early diagnosis of BO is usually difficult because patients are often asymptomatic at an initial stage of the disease and pathologic findings are available mostly at the late stages. Therefore, the diagnosis of the disease is based on the pulmonary function test using the National Institute of Health consensus criteria. Here, we report a case of slowly progressive BO. A biopsy specimen at an early stage demonstrated alveolar destruction with lymphocyte infiltration in bronchial walls and mild narrowing of bronchioles without fibrosis, those were strongly indicative of initial pathologic changes of BO. Definitive BO followed, which was proven by both clinical course and autopsy. While alloreactive lymphocytes associated with chronic graft-versus-host disease are believed to initiate BO, we present a rare case that directly implies such a scenario.", "classifications": [ { "id": "Nishikii", "label": "Group Nishikii", "parent": "Shintaku", "type": "group" }, { "id": "Shintaku", "label": "Team Shintaku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Rie", "last_name": "Nakamoto-Matsubara", "name": null }, { "creator_type": "author", "first_name": "Hidekazu", "last_name": "Nishikii", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Yamada", "name": null }, { "creator_type": "author", "first_name": "Masafumi", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Yuichi", "last_name": "Hasegawa", "name": null }, { "creator_type": "author", "first_name": "Naoki", "last_name": "Kurita", "name": null }, { "creator_type": "author", "first_name": "Naoshi", "last_name": "Obara", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Okoshi", "name": null }, { "creator_type": "author", "first_name": "Kazumi", "last_name": "Suzukawa", "name": null }, { "creator_type": "author", "first_name": "Yasuhisa", "last_name": "Yokoyama", "name": null }, { "creator_type": "author", "first_name": "Mamiko", "last_name": "Sakata-Yanagimoto", "name": null }, { "creator_type": "author", "first_name": "Masayuki", "last_name": "Noguchi", "name": null }, { "creator_type": "author", "first_name": "Shigeru", "last_name": "Chiba", "name": null } ], "identifiers": { "doi": { "normalized": "10.1155/2012/957612" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "22957280" } }, "mesh": [], "publication": { "conference_name": null, "date": "2012", "date_precision": "year", "issue": "", "normalized_date": "2012", "pages": "", "proceedings_title": null, "publisher": "", "title": "Case Reports in Hematology", "volume": "2012", "year": 2012 }, "ssbd": { "database": [], "repository": [] }, "title": "Early Pathologic Findings of Bronchiolitis Obliterans after Allogeneic Hematopoietic Stem Cell Transplantation: A Proposal from a Case.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "In the mammalian brain, the suprachiasmatic nucleus (SCN) of the anterior hypothalamus is considered to be the principal circadian pacemaker, keeping the rhythm of most physiological and behavioral processes on the basis of light/dark cycles. Because restriction of food availability to a certain time of day elicits anticipatory behavior even after ablation of the SCN, such behavior has been assumed to be under the control of another circadian oscillator. According to recent studies, however, mutant mice lacking circadian clock function exhibit normal food-anticipatory activity (FAA), a daily increase in locomotor activity preceding periodic feeding, suggesting that FAA is independent of the known circadian oscillator. To investigate the molecular basis of FAA, we examined oscillatory properties in mice lacking molecular clock components. Mice with SCN lesions or with mutant circadian periods were exposed to restricted feeding schedules at periods within and outside circadian range. Periodic feeding led to the entrainment of FAA rhythms only within a limited circadian range. Cry1−/− mice, which are known to be a “short-period mutant,” entrained to a shorter period of feeding cycles than did Cry2−/− mice. This result indicated that the intrinsic periods of FAA rhythms are also affected by Cry deficiency. Bmal1−/− mice, deficient in another essential element of the molecular clock machinery, exhibited a pre-feeding increase of activity far from circadian range, indicating a deficit in circadian oscillation. We propose that mice possess a food-entrainable pacemaker outside the SCN in which canonical clock genes such as Cry1, Cry2 and Bmal1 play essential roles in regulating FAA in a circadian oscillatory manner.", "classifications": [ { "id": "Mochizuki", "label": "Group Mochizuki", "parent": "Eiraku", "type": "group" }, { "id": "Eiraku", "label": "Team Eiraku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Nana N.", "last_name": "Takasu", "name": null }, { "creator_type": "author", "first_name": "Gen", "last_name": "Kurosawa", "name": null }, { "creator_type": "author", "first_name": "Isao T.", "last_name": "Tokuda", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Mochizuki", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Todo", "name": null }, { "creator_type": "author", "first_name": "Wataru", "last_name": "Nakamura", "name": null } ], "identifiers": { "doi": { "normalized": "10.1371/journal.pone.0048892" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "23145013" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Anticipation, Psychological", "descriptor_ui": "D059031", "major_topic": false }, { "descriptor": "ARNTL Transcription Factors", "descriptor_ui": "D056930", "major_topic": false }, { "descriptor": "Behavior, Animal", "descriptor_ui": "D001522", "major_topic": false }, { "descriptor": "Circadian Rhythm", "descriptor_ui": "D002940", "major_topic": true }, { "descriptor": "Cryptochromes", "descriptor_ui": "D056931", "major_topic": false }, { "descriptor": "Feeding Behavior", "descriptor_ui": "D005247", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Suprachiasmatic Nucleus", "descriptor_ui": "D013493", "major_topic": false } ], "publication": { "conference_name": null, "date": "2012", "date_precision": "year", "issue": "11", "normalized_date": "2012", "pages": "", "proceedings_title": null, "publisher": "", "title": "PLoS ONE", "volume": "7", "year": 2012 }, "ssbd": { "database": [], "repository": [] }, "title": "Circadian Regulation of Food-Anticipatory Activity in Molecular Clock–Deficient Mice.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Directing the axis of cell division toward extrinsic and intrinsic cues plays a fundamental role in morphogenesis, asymmetric cell division, and stem cell self-renewal. Recent studies highlight the misorientation of the cell division axis as a cause of mammalian diseases, including polycystic kidney disease. Although the core regulators for oriented cell division have been identified in invertebrate model systems, we still have an imprecise picture of the relevant signaling networks in the mammalian system. The reasons for this include the lack of established approaches in mammalian cells to survey the molecules required for the spindle orientation. Here we summarize our recent study on a genome-scale RNA-mediated interference screen of human kinases to identify a new player for the oriented cell division in both culture cells and developing mammalian tissues.", "classifications": [ { "id": "Toyoshima", "label": "Group Toyoshima", "parent": "Toyoshima", "type": "group" }, { "id": "Toyoshima", "label": "Team Toyoshima", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Shigeru", "last_name": "Matsumura", "name": null }, { "creator_type": "author", "first_name": "Fumiko", "last_name": "Toyoshima", "name": null } ], "identifiers": { "doi": { "normalized": "10.1247/csf.12011" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "22672996" } }, "mesh": [ { "descriptor": "Cell Division", "descriptor_ui": "D002455", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Integrin beta1", "descriptor_ui": "D019012", "major_topic": false }, { "descriptor": "Proto-Oncogene Proteins c-abl", "descriptor_ui": "D016315", "major_topic": false }, { "descriptor": "RNA Interference", "descriptor_ui": "D034622", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Spindle Apparatus", "descriptor_ui": "D008941", "major_topic": false } ], "publication": { "conference_name": null, "date": "2012", "date_precision": "year", "issue": "2", "normalized_date": "2012", "pages": "81-87", "proceedings_title": null, "publisher": "", "title": "Cell structure and function", "volume": "37", "year": 2012 }, "ssbd": { "database": [], "repository": [] }, "title": "ABL1 joins the cadre of spindle orientation machinery.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Background: Proteolytic degradation of the extracellular matrix (ECM) is a key event in tumour metastasis and invasion. Matrix metalloproteinases (MMPs) are a family of endopeptidases that degrade most of the components of the ECM. Several broad-spectrum MMP inhibitors (MMPIs) have been developed, but have had little success due to side effects. Thus, it is important to develop mathematical methods to provide new drug treatment strategies. Matrix metalloproteinase 2 (MMP2) activation occurs via a mechanism involving complex formation that consists of membrane type 1 MMP (MT1-MMP), tissue inhibitor of matrix metalloproteinase 2 (TIMP2) and MMP2. Here, we focus on developing a method for analysing the complex formation process. Results: We used control analysis to investigate inhibitor responses in complex formation processes. The essence of the analysis is to define the response coefficient which measures the inhibitory efficiency, a small fractional change of concentration of a targeting molecule in response to a small fractional change of concentration of an inhibitor. First, by using the response coefficient, we investigated models for general classes of complex formation processes: chain reaction systems composed of ordered steps, and chain reaction systems and site-binding reaction systems composed of unordered multi-branched steps. By analysing the ordered step models, we showed that parameter-independent inequalities between the response coefficients held. For the unordered multi-branched step models, we showed that independence of the response coefficients with respect to equilibrium constants held. As an application of our analysis, we discuss a mathematical model for the MMP2 activation process. By putting the experimentally derived parameter values into the model, we were able to conclude that the TIMP2 and MMP2 interaction is the most efficient interaction to consider in selecting inhibitors. Conclusions: Our result identifies a new drug target in the process of the MMP2 activation. Thus, our analysis will provide new insight into the design of more efficient drug strategies for cancer treatment.", "classifications": [ { "id": "Suzuki", "label": "Group Suzuki", "parent": "Takekawa", "type": "group" }, { "id": "Takekawa", "label": "Team Takekawa", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Takashi", "last_name": "Saitou", "name": null }, { "creator_type": "author", "first_name": "Keiko", "last_name": "Itano", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Hoshino", "name": null }, { "creator_type": "author", "first_name": "Naohiko", "last_name": "Koshikawa", "name": null }, { "creator_type": "author", "first_name": "Motoharu", "last_name": "Seiki", "name": null }, { "creator_type": "author", "first_name": "Kazuhisa", "last_name": "Ichikawa", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Suzuki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1186/1742-4682-9-33" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "22863329" } }, "mesh": [ { "descriptor": "Endopeptidases", "descriptor_ui": "D010450", "major_topic": false }, { "descriptor": "Extracellular Matrix", "descriptor_ui": "D005109", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Kinetics", "descriptor_ui": "D007700", "major_topic": false }, { "descriptor": "Matrix Metalloproteinase 14", "descriptor_ui": "D053511", "major_topic": false }, { "descriptor": "Matrix Metalloproteinase 2", "descriptor_ui": "D020778", "major_topic": false }, { "descriptor": "Models, Theoretical", "descriptor_ui": "D008962", "major_topic": false }, { "descriptor": "Neoplasm Invasiveness", "descriptor_ui": "D009361", "major_topic": false }, { "descriptor": "Protease Inhibitors", "descriptor_ui": "D011480", "major_topic": false }, { "descriptor": "Systems Theory", "descriptor_ui": "D013598", "major_topic": false }, { "descriptor": "Tissue Inhibitor of Metalloproteinase-2", "descriptor_ui": "D019716", "major_topic": false } ], "publication": { "conference_name": null, "date": "2012", "date_precision": "year", "issue": "", "normalized_date": "2012", "pages": "33", "proceedings_title": null, "publisher": "", "title": "Theoretical Biology & Medical Modelling", "volume": "9", "year": 2012 }, "ssbd": { "database": [], "repository": [] }, "title": "Control and inhibition analysis of complex formation processes.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Background: Central administration of γ-amino butyric acid (GABA) induces lower body temperature in animals in hot ambient air. However, it is still unknown whether oral GABA administration affects temperature regulation at rest in a hot environment in humans. Therefore, in the present study, we specifically hypothesized that systemic administration of GABA in humans would induce hypothermia in a hot environment and that this response would be observed in association with decreased heat production. Methods: Eight male participants drank a 200-ml sports drink with 1 g of GABA (trial G) or without GABA (trial C), then rested for 30 minutes in a sitting position in a hot environment (ambient air temperature 33°C, relative humidity 50%). Results: We found that changes in esophageal temperature from before drinking the sports drink were lower in trial G than in trial C (-0.046 ± 0.079°C vs 0.001 ± 0.063°C; P < 0.05), with lower heat production calculated by oxygen consumption (41 ± 5 W/m2 vs 47 ± 8 W/m2; P < 0.05). Conclusions: In this study, we have demonstrated that a single oral administration of GABA induced a larger decrease in body core temperature compared to a control condition during rest in a hot environment and that this response was concomitant with a decrease in total heat production.", "classifications": [ { "id": "Suzuki", "label": "Group Suzuki", "parent": "Takekawa", "type": "group" }, { "id": "Takekawa", "label": "Team Takekawa", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Taiki", "last_name": "Miyazawa", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Kawabata", "name": null }, { "creator_type": "author", "first_name": "Kazunobu", "last_name": "Okazaki", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Daiki", "last_name": "Imai", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Hamamoto", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Matsumura", "name": null }, { "creator_type": "author", "first_name": "Toshiaki", "last_name": "Miyagawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1186/1880-6805-31-3" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "22738209" } }, "mesh": [ { "descriptor": "Administration, Oral", "descriptor_ui": "D000284", "major_topic": false }, { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Analysis of Variance", "descriptor_ui": "D000704", "major_topic": false }, { "descriptor": "Body Temperature", "descriptor_ui": "D001831", "major_topic": false }, { "descriptor": "Body Temperature Regulation", "descriptor_ui": "D001833", "major_topic": false }, { "descriptor": "Double-Blind Method", "descriptor_ui": "D004311", "major_topic": false }, { "descriptor": "gamma-Aminobutyric Acid", "descriptor_ui": "D005680", "major_topic": false }, { "descriptor": "Hot Temperature", "descriptor_ui": "D006358", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Oxygen Consumption", "descriptor_ui": "D010101", "major_topic": false }, { "descriptor": "Placebos", "descriptor_ui": "D010919", "major_topic": false }, { "descriptor": "Thermogenesis", "descriptor_ui": "D022722", "major_topic": false } ], "publication": { "conference_name": null, "date": "2012", "date_precision": "year", "issue": "1", "normalized_date": "2012", "pages": "3", "proceedings_title": null, "publisher": "", "title": "Journal of Physiological Anthropology", "volume": "31", "year": 2012 }, "ssbd": { "database": [], "repository": [] }, "title": "Oral administration of γ-aminobutyric acid affects heat production in a hot environment in resting humans.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Microscopic biological processes have extraordinary complexity and variety at the sub-cellular, intra-cellular, and multi-cellular levels. In dealing with such complex phenomena, conceptual and theoretical frameworks are crucial, which enable us to understand seemingly different intra- and inter-cellular phenomena from unified viewpoints. Decision-making is one such concept that has attracted much attention recently. Since a number of cellular behavior can be regarded as processes to make specific actions in response to external stimuli, decision-making can cover and has been used to explain a broad range of different cellular phenomena [Balazsi et al. (Cell 144(6):910, 2011), Zeng et al. (Cell 141(4):682, 2010)]. Decision-making is also closely related to cellular information-processing because appropriate decisions cannot be made without exploiting the information that the external stimuli contain. Efficiency of information transduction and processing by intra-cellular networks determines the amount of information obtained, which in turn limits the efficiency of subsequent decision-making. Furthermore, information-processing itself can serve as another concept that is crucial for understanding of other biological processes than decision-making. In this work, we review recent theoretical developments on cellular decision-making and information-processing by focusing on the relation between these two concepts.", "classifications": [ { "id": "Kobayashi", "label": "Group Kobayashi", "parent": "Wakamoto", "type": "group" }, { "id": "Wakamoto", "label": "Team Wakamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Tetsuya J.", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Kamimura", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/978-1-4419-7210-1_16" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "22161335" } }, "mesh": [ { "descriptor": "Adaptation, Physiological", "descriptor_ui": "D000222", "major_topic": false }, { "descriptor": "Algorithms", "descriptor_ui": "D000465", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Apoptosis", "descriptor_ui": "D017209", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Models, Biological", "descriptor_ui": "D008954", "major_topic": true }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false } ], "publication": { "conference_name": null, "date": "2012", "date_precision": "year", "issue": "", "normalized_date": "2012", "pages": "275-291", "proceedings_title": null, "publisher": "", "title": "Advances in experimental medicine and biology", "volume": "736", "year": 2012 }, "ssbd": { "database": [], "repository": [] }, "title": "Theoretical aspects of cellular decision-making and information-processing.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Recent experimental observations suggest that cells can show relatively precise and reliable responses to external signals even though substantial noise is inevitably involved in the signals. An intriguing question is the way how cells can manage to do it. One possible way to realize such response for a cell is to evolutionary develop and optimize its intracellular signaling pathways so as to extract relevant information from the noisy signal. We recently demonstrated that certain intracellular signaling reactions could actually conduct statistically optimal information processing. In this paper, we clarify that such optimal reaction operates near bifurcation point. This result suggests that critical-like phenomena in the single-cell level may be linked to efficient information processing inside a cell. In addition, improving the performance of response in the single-cell level is not the only way for cells to realize reliable response. Another possible strategy is to integrate information of individual cells by cell-to-cell interaction such as quorum sensing. Since cell-to-cell interaction is a common phenomenon, it is equally important to investigate how cells can integrate their information by cell-to-cell interaction to realize efficient information processing in the population level. In this paper, we consider roles and benefits of cell-to-cell interaction by considering integrations of obtained information of individuals with the other cells from the viewpoint of information processing. We also demonstrate that, by introducing cell movement, spatial organizations can spontaneously emerge as a result of efficient responses of the population to external signals.", "classifications": [ { "id": "Kobayashi", "label": "Group Kobayashi", "parent": "Wakamoto", "type": "group" }, { "id": "Wakamoto", "label": "Team Wakamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Atsushi", "last_name": "Kamimura", "name": null }, { "creator_type": "author", "first_name": "Tetsuya J.", "last_name": "Kobayashi", "name": null } ], "identifiers": { "doi": { "normalized": "10.3389/fphys.2012.00203" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "22707939" } }, "mesh": [], "publication": { "conference_name": null, "date": "2012", "date_precision": "year", "issue": "", "normalized_date": "2012", "pages": "", "proceedings_title": null, "publisher": "", "title": "Frontiers in Physiology", "volume": "3", "year": 2012 }, "ssbd": { "database": [], "repository": [] }, "title": "Information Processing and Integration with Intracellular Dynamics Near Critical Point.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "To further optimize the culturing of preimplantation embryos, we undertook metabolomic analysis of relevant culture media using capillary electrophoresis time-of-flight mass spectrometry (CE-TOFMS). We detected 28 metabolites: 23 embryo-excreted metabolites including 16 amino acids and 5 media-derived metabolites (e.g., octanoate, a medium-chain fatty acid (MCFA)). Due to the lack of information on MCFAs in mammalian preimplantation development, this study examined octanoate as a potential alternative energy source for preimplantation embryo cultures. No embryos survived in culture media lacking FAs, pyruvate, and glucose, but supplementation of octanoate rescued the embryonic development. Immunoblotting showed significant expression of acyl-CoA dehydrogenase and hydroxyacyl-CoA dehydrogenase, important enzymes for ss-oxidation of MCFAs, in preimplantation embryo. Furthermore, CE-TOFMS traced [1-(13)C(8)] octanoate added to the culture media into intermediate metabolites of the TCA cycle via ss-oxidation in mitochondria. These results are the first demonstration that octanoate could provide an efficient alternative energy source throughout preimplantation development.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Mitsutoshi", "last_name": "Yamada", "name": null }, { "creator_type": "author", "first_name": "Kazumi", "last_name": "Takanashi", "name": null }, { "creator_type": "author", "first_name": "Toshio", "last_name": "Hamatani", "name": null }, { "creator_type": "author", "first_name": "Akiyoshi", "last_name": "Hirayama", "name": null }, { "creator_type": "author", "first_name": "Hidenori", "last_name": "Akutsu", "name": null }, { "creator_type": "author", "first_name": "Tomoko", "last_name": "Fukunaga", "name": null }, { "creator_type": "author", "first_name": "Seiji", "last_name": "Ogawa", "name": null }, { "creator_type": "author", "first_name": "Kana", "last_name": "Sugawara", "name": null }, { "creator_type": "author", "first_name": "Kosaku", "last_name": "Shinoda", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Akihiro", "last_name": "Umezawa", "name": null }, { "creator_type": "author", "first_name": "Naoaki", "last_name": "Kuji", "name": null }, { "creator_type": "author", "first_name": "Yasunori", "last_name": "Yoshimura", "name": null }, { "creator_type": "author", "first_name": "Masaru", "last_name": "Tomita", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/srep00930" }, "pmcid": { "normalized": "PMC3514685" }, "pmid": { "normalized": "23226596" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Blastocyst", "descriptor_ui": "D001755", "major_topic": true }, { "descriptor": "Caprylates", "descriptor_ui": "D002210", "major_topic": false }, { "descriptor": "Citric Acid Cycle", "descriptor_ui": "D002952", "major_topic": false }, { "descriptor": "Electrophoresis, Capillary", "descriptor_ui": "D019075", "major_topic": false }, { "descriptor": "Energy Metabolism", "descriptor_ui": "D004734", "major_topic": false }, { "descriptor": "Fatty Acids", "descriptor_ui": "D005227", "major_topic": false }, { "descriptor": "Gene Expression Regulation", "descriptor_ui": "D005786", "major_topic": false }, { "descriptor": "Mass Spectrometry", "descriptor_ui": "D013058", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Oxidation-Reduction", "descriptor_ui": "D010084", "major_topic": false } ], "publication": { "conference_name": null, "date": "2012", "date_precision": "year", "issue": "", "normalized_date": "2012", "pages": "930", "proceedings_title": null, "publisher": "", "title": "Scientific reports", "volume": "2", "year": 2012 }, "ssbd": { "database": [], "repository": [] }, "title": "A medium-chain fatty acid as an alternative energy source in mouse preimplantation development.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Background: Nitric oxide is a key molecule not only in the cardiovascular system, but also in the metabolic-endocrine system. The purpose of this study was to examine possible associations of the NOS3 T-786C polymorphism (rs2070744) with serum lipid levels on the basis of lifestyle factors for tailoring prevention of dyslipidemia. Methods: For this cross-sectional study, a total of 2226 subjects aged 35 to 69 years (1084 men and 1142 women) were selected from Japanese participants in the Japan Multi-Institutional Collaborative Cohort (J-MICC) Study. They were recruited in eight areas throughout Japan between February 2004 and November 2008. Results: In a stratified analysis by leisure-time physical activity, the likelihood of hypertriglyceridemia (serum triglyceride levels ≥ 150 mg/dL) among subjects with the C allele was significantly lower than those without it in the active group (OR = 0.43, 95% CI = 0.22-0.84 in the fasting group), but not in the sedentary group. A gene-environment interaction between the T-786C polymorphism and leisure-time physical activity for hypertriglyceridemia was significant (P = 0.007 in the fasting group). Additionally, serum triglyceride levels (mean ± SD) across leisure-time physical activity classes decreased significantly only in the TC + CC genotype group (111 ± 60 mg/dL for sedentary, 95 ± 48 mg/dL for moderately active, 88 ± 44 mg/dL for very active, P for trend = 0.008 in the fasting group), but not in the TT genotype group. Total cholesterol, high-density lipoprotein (HDL) cholesterol, and non-HDL cholesterol levels had no significant association with the polymorphism. Conclusions: This study suggests that the NOS3 T-786C polymorphism modifies the effect of leisure-time physical activity on serum triglyceride levels.", "classifications": [ { "id": "Tanaka", "label": "Group Tanaka", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Takahiro", "last_name": "Higashibata", "name": null }, { "creator_type": "author", "first_name": "Nobuyuki", "last_name": "Hamajima", "name": null }, { "creator_type": "author", "first_name": "Mariko", "last_name": "Naito", "name": null }, { "creator_type": "author", "first_name": "Sayo", "last_name": "Kawai", "name": null }, { "creator_type": "author", "first_name": "Guang", "last_name": "Yin", "name": null }, { "creator_type": "author", "first_name": "Sadao", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Yoshikuni", "last_name": "Kita", "name": null }, { "creator_type": "author", "first_name": "Hideshi", "last_name": "Niimura", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Imaizumi", "name": null }, { "creator_type": "author", "first_name": "Keizo", "last_name": "Ohnaka", "name": null }, { "creator_type": "author", "first_name": "Kokichi", "last_name": "Arisawa", "name": null }, { "creator_type": "author", "first_name": "Masako", "last_name": "Shigeta", "name": null }, { "creator_type": "author", "first_name": "Hidemi", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Haruo", "last_name": "Mikami", "name": null }, { "creator_type": "author", "first_name": "Michiaki", "last_name": "Kubo", "name": null }, { "creator_type": "author", "first_name": "Hideo", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Wakai", "name": null } ], "identifiers": { "doi": { "normalized": "10.1186/1476-511x-11-150" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "23122449" } }, "mesh": [ { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Alleles", "descriptor_ui": "D000483", "major_topic": false }, { "descriptor": "Dyslipidemias", "descriptor_ui": "D050171", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Genetic Association Studies", "descriptor_ui": "D056726", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Japan", "descriptor_ui": "D007564", "major_topic": false }, { "descriptor": "Leisure Activities", "descriptor_ui": "D007899", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Motor Activity", "descriptor_ui": "D009043", "major_topic": true }, { "descriptor": "Nitric Oxide Synthase Type III", "descriptor_ui": "D052250", "major_topic": false }, { "descriptor": "Polymorphism, Single Nucleotide", "descriptor_ui": "D020641", "major_topic": false }, { "descriptor": "Risk Factors", "descriptor_ui": "D012307", "major_topic": false }, { "descriptor": "Triglycerides", "descriptor_ui": "D014280", "major_topic": true } ], "publication": { "conference_name": null, "date": "2012", "date_precision": "year", "issue": "", "normalized_date": "2012", "pages": "150", "proceedings_title": null, "publisher": "", "title": "Lipids in Health and Disease", "volume": "11", "year": 2012 }, "ssbd": { "database": [], "repository": [] }, "title": "eNOS genotype modifies the effect of leisure-time physical activity on serum triglyceride levels in a Japanese population.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Increased information on the encoded mammalian genome is expected to facilitate an integrated understanding of complex anatomical structure and function based on the knowledge of gene products. Determination of gene expression-anatomy associations is crucial for this understanding. To elicit the association in the three-dimensional (3D) space, we introduce a novel technique for comprehensive mapping of endogenous gene expression into a web-accessible standard space: Transcriptome Tomography. The technique is based on conjugation of sequential tissue-block sectioning, all fractions of which are used for molecular measurements of gene expression densities, and the block- face imaging, which are used for 3D reconstruction of the fractions. To generate a 3D map, tissues are serially sectioned in each of three orthogonal planes and the expression density data are mapped using a tomographic technique. This rapid and unbiased mapping technique using a relatively small number of original data points allows researchers to create their own expression maps in the broad anatomical context of the space. In the first instance we generated a dataset of 36,000 maps, reconstructed from data of 61 fractions measured with microarray, covering the whole mouse brain (ViBrism: http://vibrism.riken.jp/3dviewer/ex/index.html) in one month. After computational estimation of the mapping accuracy we validated the dataset against existing data with respect to the expression location and density. To demonstrate the relevance of the framework, we showed disease related expression of Huntington's disease gene and Bdnf. Our tomographic approach is applicable to analysis of any biological molecules derived from frozen tissues, organs and whole embryos, and the maps are spatially isotropic and well suited to the analysis in the standard space (e.g. Waxholm Space for brain-atlas databases). This will facilitate research creating and using open-standards for a molecular-based understanding of complex structures; and will contribute to new insights into a broad range of biological and medical questions.", "classifications": [ { "id": "Nikaido", "label": "Group Nikaido", "parent": "Fujiwara", "type": "group" }, { "id": "Fujiwara", "label": "Team Fujiwara", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yuko", "last_name": "Okamura-Oho", "name": null }, { "creator_type": "author", "first_name": "Kazuro", "last_name": "Shimokawa", "name": null }, { "creator_type": "author", "first_name": "Satoko", "last_name": "Takemoto", "name": null }, { "creator_type": "author", "first_name": "Asami", "last_name": "Hirakiyama", "name": null }, { "creator_type": "author", "first_name": "Sakiko", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Tsujimura", "name": null }, { "creator_type": "author", "first_name": "Masaomi", "last_name": "Nishimura", "name": null }, { "creator_type": "author", "first_name": "Takeya", "last_name": "Kasukawa", "name": null }, { "creator_type": "author", "first_name": "Koh-hei", "last_name": "Masumoto", "name": null }, { "creator_type": "author", "first_name": "Itoshi", "last_name": "Nikaido", "name": null }, { "creator_type": "author", "first_name": "Yasufumi", "last_name": "Shigeyoshi", "name": null }, { "creator_type": "author", "first_name": "Hiroki R.", "last_name": "Ueda", "name": null }, { "creator_type": "author", "first_name": "Gang", "last_name": "Song", "name": null }, { "creator_type": "author", "first_name": "James", "last_name": "Gee", "name": null }, { "creator_type": "author", "first_name": "Ryutaro", "last_name": "Himeno", "name": null }, { "creator_type": "author", "first_name": "Hideo", "last_name": "Yokota", "name": null } ], "identifiers": { "doi": { "normalized": "10.1371/journal.pone.0045373" }, "pmcid": { "normalized": "PMC3446890" }, "pmid": { "normalized": "23028969" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Brain", "descriptor_ui": "D001921", "major_topic": false }, { "descriptor": "Gene Expression Profiling", "descriptor_ui": "D020869", "major_topic": false }, { "descriptor": "Huntington Disease", "descriptor_ui": "D006816", "major_topic": false }, { "descriptor": "Imaging, Three-Dimensional", "descriptor_ui": "D021621", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Transcriptome", "descriptor_ui": "D059467", "major_topic": false } ], "publication": { "conference_name": null, "date": "2012", "date_precision": "year", "issue": "9", "normalized_date": "2012", "pages": "e45373", "proceedings_title": null, "publisher": "", "title": "PloS one", "volume": "7", "year": 2012 }, "ssbd": { "database": [], "repository": [] }, "title": "Transcriptome tomography for brain analysis in the web-accessible anatomical space.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: Although several reports have described a possible association between DNA repair genes and pancreatic cancer (PC) in smokers, this association has not been fully evaluated in an Asian population. We assessed the impact of genetic polymorphisms in the base excision repair (BER) pathway on PC risk among Japanese. METHODS: This case-control study compared the frequency of 5 single-nucleotide polymorphisms (SNPs) of BER genes, namely rs1052133 in OGG1, rs1799782 and rs25487 in XRCC1, rs1130409 in APE1, and rs1136410 in PARP1. SNPs were investigated using the TaqMan assay in 185 PC cases and 1465 controls. Associations of PC risk with genetic polymorphisms and gene-environment interaction were examined with an unconditional logistic regression model. Exposure to risk factors was assessed from the results of a self-administered questionnaire. We also performed haplotype-based analysis. RESULTS: We observed that the minor allele of rs25487 in XRCC1 was significantly associated with PC risk in the per-allele model (odds ratio = 1.29, CI = 1.01-1.65; trend P = 0.043). Haplotype analysis of XRCC1 also showed a statistically significant association with PC risk. No statistically significant interaction between XRCC1 polymorphisms and smoking status was seen. CONCLUSIONS: Our findings suggest that XRCC1 polymorphisms affect PC risk in Japanese.", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Makoto", "last_name": "Nakao", "name": null }, { "creator_type": "author", "first_name": "Satoyo", "last_name": "Hosono", "name": null }, { "creator_type": "author", "first_name": "Hidemi", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Miki", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Nobumasa", "last_name": "Mizuno", "name": null }, { "creator_type": "author", "first_name": "Shigeki", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Yamao", "name": null }, { "creator_type": "author", "first_name": "Ryuzo", "last_name": "Ueda", "name": null }, { "creator_type": "author", "first_name": "Kazuo", "last_name": "Tajima", "name": null }, { "creator_type": "author", "first_name": "Hideo", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Keitaro", "last_name": "Matsuo", "name": null } ], "identifiers": { "doi": { "normalized": "10.2188/jea.je20120010" }, "pmcid": { "normalized": "PMC3798558" }, "pmid": { "normalized": "22850545" } }, "mesh": [ { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Asian People", "descriptor_ui": "D044466", "major_topic": false }, { "descriptor": "Case-Control Studies", "descriptor_ui": "D016022", "major_topic": false }, { "descriptor": "DNA Glycosylases", "descriptor_ui": "D045647", "major_topic": false }, { "descriptor": "DNA Repair", "descriptor_ui": "D004260", "major_topic": false }, { "descriptor": "DNA-(Apurinic or Apyrimidinic Site) Lyase", "descriptor_ui": "D043603", "major_topic": false }, { "descriptor": "DNA-Binding Proteins", "descriptor_ui": "D004268", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Gene Frequency", "descriptor_ui": "D005787", "major_topic": false }, { "descriptor": "Gene-Environment Interaction", "descriptor_ui": "D059647", "major_topic": false }, { "descriptor": "Genetic Predisposition to Disease", "descriptor_ui": "D020022", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Japan", "descriptor_ui": "D007564", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Pancreatic Neoplasms", "descriptor_ui": "D010190", "major_topic": false }, { "descriptor": "Poly (ADP-Ribose) Polymerase-1", "descriptor_ui": "D000071137", "major_topic": false }, { "descriptor": "Poly(ADP-ribose) Polymerases", "descriptor_ui": "D011065", "major_topic": false }, { "descriptor": "Polymorphism, Single Nucleotide", "descriptor_ui": "D020641", "major_topic": false }, { "descriptor": "Risk Factors", "descriptor_ui": "D012307", "major_topic": false }, { "descriptor": "Smoking", "descriptor_ui": "D012907", "major_topic": false }, { "descriptor": "X-ray Repair Cross Complementing Protein 1", "descriptor_ui": "D000076105", "major_topic": false } ], "publication": { "conference_name": null, "date": "2012", "date_precision": "year", "issue": "6", "normalized_date": "2012", "pages": "477-483", "proceedings_title": null, "publisher": "", "title": "Journal of epidemiology", "volume": "22", "year": 2012 }, "ssbd": { "database": [], "repository": [] }, "title": "Selected polymorphisms of base excision repair genes and pancreatic cancer risk in Japanese.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Organs develop distinctive morphologies to fulfill their unique functions. We used Drosophila embryonic gonads as a model to study how two different cell lineages, primordial germ cells (PGCs) and somatic gonadal precursors (SGPs), combine to form one organ. We developed a membrane GFP marker to image SGP behaviors live. These studies show that a combination of SGP cell shape changes and inward movement of anterior and posterior SGPs leads to the compaction of the spherical gonad. This process is disrupted in mutants of the actin regulator, enabled (ena). We show that Ena coordinates these cell shape changes and the inward movement of the SGPs, and Ena affects the intracellular localization of DE-cadherin (DE-cad). Mathematical simulation based on these observations suggests that changes in DE-cad localization can generate the forces needed to compact an elongated structure into a sphere. We propose that Ena regulates force balance in the SGPs by sequestering DE-cad, leading to the morphogenetic movement required for gonad compaction.", "classifications": [ { "id": "Ishihara", "label": "Group Ishihara", "parent": "Sawai", "type": "group" }, { "id": "Sawai", "label": "Team Sawai", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Hiroko", "last_name": "Sano", "name": null }, { "creator_type": "author", "first_name": "Prabhat S.", "last_name": "Kunwar", "name": null }, { "creator_type": "author", "first_name": "Andrew D.", "last_name": "Renault", "name": null }, { "creator_type": "author", "first_name": "Vitor", "last_name": "Barbosa", "name": null }, { "creator_type": "author", "first_name": "Ivan B. N.", "last_name": "Clark", "name": null }, { "creator_type": "author", "first_name": "Shuji", "last_name": "Ishihara", "name": null }, { "creator_type": "author", "first_name": "Kaoru", "last_name": "Sugimura", "name": null }, { "creator_type": "author", "first_name": "Ruth", "last_name": "Lehmann", "name": null } ], "identifiers": { "doi": { "normalized": "10.1371/journal.pone.0052649" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "23300733" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cadherins", "descriptor_ui": "D015820", "major_topic": false }, { "descriptor": "Cell Shape", "descriptor_ui": "D048430", "major_topic": false }, { "descriptor": "DNA-Binding Proteins", "descriptor_ui": "D004268", "major_topic": false }, { "descriptor": "Drosophila melanogaster", "descriptor_ui": "D004331", "major_topic": false }, { "descriptor": "Drosophila Proteins", "descriptor_ui": "D029721", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Germ Cells", "descriptor_ui": "D005854", "major_topic": false }, { "descriptor": "Gonads", "descriptor_ui": "D006066", "major_topic": false }, { "descriptor": "Models, Biological", "descriptor_ui": "D008954", "major_topic": false }, { "descriptor": "Morphogenesis", "descriptor_ui": "D009024", "major_topic": false }, { "descriptor": "Organogenesis", "descriptor_ui": "D038081", "major_topic": true }, { "descriptor": "Protein Transport", "descriptor_ui": "D021381", "major_topic": false }, { "descriptor": "Stem Cells", "descriptor_ui": "D013234", "major_topic": false }, { "descriptor": "Time-Lapse Imaging", "descriptor_ui": "D059008", "major_topic": false } ], "publication": { "conference_name": null, "date": "2012", "date_precision": "year", "issue": "12", "normalized_date": "2012", "pages": "", "proceedings_title": null, "publisher": "", "title": "PLoS ONE", "volume": "7", "year": 2012 }, "ssbd": { "database": [], "repository": [] }, "title": "The Drosophila Actin Regulator ENABLED Regulates Cell Shape and Orientation during Gonad Morphogenesis.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "A method for the determination of underivatized amino acids based on capillary electrophoresis-mass spectrometry is described. To analyze free amino acids simultaneously, a low acidic pH electrolyte was used to confer positive charge on whole amino acids. All protonated amino acids migrated toward the cathode in CE and then were detected by electrospray ionization mass spectrometry with high selectivity and sensitivity. This method is simple, rapid, and selective and could be readily applied to the analysis of free amino acids in various samples.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Akiyoshi", "last_name": "Hirayama", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/978-1-61779-445-2_8" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "22125138" } }, "mesh": [ { "descriptor": "Amino Acids", "descriptor_ui": "D000596", "major_topic": false }, { "descriptor": "Electrophoresis, Capillary", "descriptor_ui": "D019075", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Limit of Detection", "descriptor_ui": "D057230", "major_topic": false }, { "descriptor": "Mass Spectrometry", "descriptor_ui": "D013058", "major_topic": false }, { "descriptor": "Neoplasm Proteins", "descriptor_ui": "D009363", "major_topic": false }, { "descriptor": "Reproducibility of Results", "descriptor_ui": "D015203", "major_topic": false }, { "descriptor": "Stomach Neoplasms", "descriptor_ui": "D013274", "major_topic": false } ], "publication": { "conference_name": null, "date": "2012", "date_precision": "year", "issue": "", "normalized_date": "2012", "pages": "77-82", "proceedings_title": null, "publisher": "", "title": "Methods in molecular biology (Clifton, N.J.)", "volume": "828", "year": 2012 }, "ssbd": { "database": [], "repository": [] }, "title": "Amino acid analysis by capillary electrophoresis-mass spectrometry.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Background: Nonalcoholic fatty liver disease (NAFLD) includes a broad range of liver pathologies from simple steatosis to cirrhosis and fibrosis, in which a subtype accompanying hepatocyte degeneration and fibrosis is classified as nonalcoholic steatohepatitis (NASH). NASH accounts for approximately 10–30% of NAFLD and causes a higher frequency of liver-related death, and its progression of NASH has been considered to be complex involving multiple genetic factors interacting with the environment and lifestyle. Principal Findings: To identify genetic factors related to NAFLD in the Japanese, we performed a genome-wide association study recruiting 529 histologically diagnosed NAFLD patients and 932 population controls. A significant association was observed for a cluster of SNPs in PNPLA3 on chromosome 22q13 with the strongest p-value of 1.4×10−10 (OR = 1.66, 95%CI: 1.43–1.94) for rs738409. Rs738409 also showed the strongest association (p = 3.6×10−6) with the histological classifications proposed by Matteoni and colleagues based on the degree of inflammation, ballooning degeneration, fibrosis and Mallory-Denk body. In addition, there were marked differences in rs738409 genotype distributions between type4 subgroup corresponding to NASH and the other three subgroups (p = 4.8×10−6, OR = 1.96, 95%CI: 1.47–2.62). Moreover, a subgroup analysis of NAFLD patients against controls showed a significant association of rs738409 with type4 (p = 1.7×10−16, OR = 2.18, 95%CI: 1.81–2.63) whereas no association was obtained for type1 to type3 (p = 0.41). Rs738409 also showed strong associations with three clinical traits related to the prognosis of NAFLD, namely, levels of hyaluronic acid (p = 4.6×10−4), HbA1c (p = 0.0011) and iron deposition in the liver (p = 5.6×10−4). Conclusions: With these results we clearly demonstrated that Matteoni type4 NAFLD is both a genetically and clinically different subset from the other spectrums of the disease and that the PNPLA3 gene is strongly associated with the progression of NASH in Japanese population.", "classifications": [ { "id": "Tanaka", "label": "Group Tanaka", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Takahisa", "last_name": "Kawaguchi", "name": null }, { "creator_type": "author", "first_name": "Yoshio", "last_name": "Sumida", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Umemura", "name": null }, { "creator_type": "author", "first_name": "Keitaro", "last_name": "Matsuo", "name": null }, { "creator_type": "author", "first_name": "Meiko", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Toshinari", "last_name": "Takamura", "name": null }, { "creator_type": "author", "first_name": "Kohichiroh", "last_name": "Yasui", "name": null }, { "creator_type": "author", "first_name": "Toshiji", "last_name": "Saibara", "name": null }, { "creator_type": "author", "first_name": "Etsuko", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Miwa", "last_name": "Kawanaka", "name": null }, { "creator_type": "author", "first_name": "Sumio", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Sumio", "last_name": "Kawata", "name": null }, { "creator_type": "author", "first_name": "Yasuharu", "last_name": "Imai", "name": null }, { "creator_type": "author", "first_name": "Miki", "last_name": "Kokubo", "name": null }, { "creator_type": "author", "first_name": "Toshihide", "last_name": "Shima", "name": null }, { "creator_type": "author", "first_name": "Hyohun", "last_name": "Park", "name": null }, { "creator_type": "author", "first_name": "Hideo", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Kazuo", "last_name": "Tajima", "name": null }, { "creator_type": "author", "first_name": "Ryo", "last_name": "Yamada", "name": null }, { "creator_type": "author", "first_name": "Fumihiko", "last_name": "Matsuda", "name": null } ], "identifiers": { "doi": { "normalized": "10.1371/journal.pone.0038322" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "22719876" } }, "mesh": [ { "descriptor": "Acyltransferases", "descriptor_ui": "D000217", "major_topic": false }, { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Case-Control Studies", "descriptor_ui": "D016022", "major_topic": false }, { "descriptor": "Chromosomes, Human, Pair 22", "descriptor_ui": "D002892", "major_topic": false }, { "descriptor": "Fatty Liver", "descriptor_ui": "D005234", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Genome-Wide Association Study", "descriptor_ui": "D055106", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Japan", "descriptor_ui": "D007564", "major_topic": false }, { "descriptor": "Lipase", "descriptor_ui": "D008049", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Membrane Proteins", "descriptor_ui": "D008565", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Phospholipases A2, Calcium-Independent", "descriptor_ui": "D054512", "major_topic": false }, { "descriptor": "Polymorphism, Single Nucleotide", "descriptor_ui": "D020641", "major_topic": true }, { "descriptor": "Severity of Illness Index", "descriptor_ui": "D012720", "major_topic": true } ], "publication": { "conference_name": null, "date": "2012", "date_precision": "year", "issue": "6", "normalized_date": "2012", "pages": "", "proceedings_title": null, "publisher": "", "title": "PLoS ONE", "volume": "7", "year": 2012 }, "ssbd": { "database": [], "repository": [] }, "title": "Genetic Polymorphisms of the Human PNPLA3 Gene Are Strongly Associated with Severity of Non-Alcoholic Fatty Liver Disease in Japanese.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Uncovering population structure is important for properly conducting association studies and for examining the demographic history of a population. Here, we examined the Japanese population substructure using data from the Japan Multi-Institutional Collaborative Cohort (J-MICC), which covers all but the northern region of Japan. Using 222 autosomal loci from 4502 subjects, we investigated population substructure by estimating FST among populations, testing population differentiation, and performing principal component analysis (PCA) and correspondence analysis (CA). All analyses revealed a low but significant differentiation between the Amami Islanders and the mainland Japanese population. Furthermore, we examined the genetic differentiation between the mainland population, Amami Islanders and Okinawa Islanders using six loci included in both the Pan-Asian SNP (PASNP) consortium data and the J-MICC data. This analysis revealed that the Amami and Okinawa Islanders were differentiated from the mainland population. In conclusion, we revealed a low but significant level of genetic differentiation between the mainland population and populations in or to the south of the Amami Islands, although genetic variation between both populations might be clinal. Therefore, the possibility of population stratification must be considered when enrolling the islander population of this area, such as in the J-MICC study.", "classifications": [ { "id": "Tanaka", "label": "Group Tanaka", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Takeshi", "last_name": "Nishiyama", "name": null }, { "creator_type": "author", "first_name": "Hirohisa", "last_name": "Kishino", "name": null }, { "creator_type": "author", "first_name": "Sadao", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Ryosuke", "last_name": "Ando", "name": null }, { "creator_type": "author", "first_name": "Hideshi", "last_name": "Niimura", "name": null }, { "creator_type": "author", "first_name": "Hirokazu", "last_name": "Uemura", "name": null }, { "creator_type": "author", "first_name": "Mikako", "last_name": "Horita", "name": null }, { "creator_type": "author", "first_name": "Keizo", "last_name": "Ohnaka", "name": null }, { "creator_type": "author", "first_name": "Nagato", "last_name": "Kuriyama", "name": null }, { "creator_type": "author", "first_name": "Haruo", "last_name": "Mikami", "name": null }, { "creator_type": "author", "first_name": "Naoyuki", "last_name": "Takashima", "name": null }, { "creator_type": "author", "first_name": "Keitaro", "last_name": "Mastuo", "name": null }, { "creator_type": "author", "first_name": "Yin", "last_name": "Guang", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Wakai", "name": null }, { "creator_type": "author", "first_name": "Nobuyuki", "last_name": "Hamajima", "name": null }, { "creator_type": "author", "first_name": "Hideo", "last_name": "Tanaka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1371/journal.pone.0035000" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "22509376" } }, "mesh": [ { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Cohort Studies", "descriptor_ui": "D015331", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Genetic Variation", "descriptor_ui": "D014644", "major_topic": true }, { "descriptor": "Geography", "descriptor_ui": "D005843", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Japan", "descriptor_ui": "D007564", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Polymorphism, Single Nucleotide", "descriptor_ui": "D020641", "major_topic": false }, { "descriptor": "Population Dynamics", "descriptor_ui": "D011157", "major_topic": true }, { "descriptor": "Population Groups", "descriptor_ui": "D044382", "major_topic": false } ], "publication": { "conference_name": null, "date": "2012", "date_precision": "year", "issue": "4", "normalized_date": "2012", "pages": "", "proceedings_title": null, "publisher": "", "title": "PLoS ONE", "volume": "7", "year": 2012 }, "ssbd": { "database": [], "repository": [] }, "title": "Detailed Analysis of Japanese Population Substructure with a Focus on the Southwest Islands of Japan.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The drive to understand how altered cellular metabolism and cancer are linked has caused a paradigm shift in the focus of cancer research. The discovery of a mutated metabolic enzyme, isocitrate dehydrogenase 1, that leads to accumulation of the oncometabolite 2-hydroxyglutarate, provided significant direct evidence that dysfunctional metabolism plays an important role in oncogenesis. Striking parallels exist with the Krebs cycle enzyme fumarate hydratase (FH), a tumor suppressor, whose mutation is associated with the development of leiomyomata, renal cysts, and tumors. Loss of FH enzymatic activity results in accumulation of intracellular fumarate which has been proposed to act as a competitive inhibitor of 2-oxoglutarate-dependent oxygenases including the hypoxia-inducible factor (HIF) hydroxylases, thus activating oncogenic HIF pathways. Interestingly, our studies have questioned the role of HIF and have highlighted other candidate mechanisms, in particular the non-enzymatic modification of cysteine residues (succination) that could lead to disruption or loss of protein functions, dysfunctional cell metabolism and cell signaling. Here, we discuss the evidence for proposing fumarate as an onco-metabolite.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Ming", "last_name": "Yang", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Patrick J.", "last_name": "Pollard", "name": null }, { "creator_type": "author", "first_name": "Julie", "last_name": "Adam", "name": null } ], "identifiers": { "doi": { "normalized": "10.3389/fonc.2012.00085" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "22866264" } }, "mesh": [], "publication": { "conference_name": null, "date": "2012", "date_precision": "year", "issue": "", "normalized_date": "2012", "pages": "", "proceedings_title": null, "publisher": "", "title": "Frontiers in Oncology", "volume": "2", "year": 2012 }, "ssbd": { "database": [], "repository": [] }, "title": "The emerging role of fumarate as an oncometabolite.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "There is an increasing call for the absolute quantification of time-resolved metabolite data. However, a number of technical issues exist, such as metabolites being modified/degraded either chemically or enzymatically during the extraction process. Additionally, capillary electrophoresis mass spectrometry (CE-MS) is incompatible with high salt concentrations often used in extraction protocols. In microbial systems, metabolite yield is influenced by the extraction protocol used and the cell disruption rate. Here we present a method that rapidly quenches metabolism using dry-ice ethanol bath and methanol N-ethylmaleimide solution (thus stabilising thiols), disrupts cells efficiently using bead-beating and avoids artefacts created by live-cell pelleting. Rapid sample processing minimised metabolite leaching. Cell weight, number and size distribution was used to calculate metabolites to an attomol/cell level. We apply this method to samples obtained from the respiratory oscillation that occurs when yeast are grown continuously.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Kalesh", "last_name": "Sasidharan", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Masaru", "last_name": "Tomita", "name": null }, { "creator_type": "author", "first_name": "Douglas B.", "last_name": "Murray", "name": null } ], "identifiers": { "doi": { "normalized": "10.1371/journal.pone.0044283" }, "pmcid": { "normalized": "PMC3430680" }, "pmid": { "normalized": "22952947" } }, "mesh": [ { "descriptor": "Calibration", "descriptor_ui": "D002138", "major_topic": false }, { "descriptor": "Electrophoresis, Capillary", "descriptor_ui": "D019075", "major_topic": false }, { "descriptor": "Ethylmaleimide", "descriptor_ui": "D005033", "major_topic": false }, { "descriptor": "Metabolome", "descriptor_ui": "D055442", "major_topic": true }, { "descriptor": "Metabolomics", "descriptor_ui": "D055432", "major_topic": false }, { "descriptor": "Saccharomyces cerevisiae", "descriptor_ui": "D012441", "major_topic": false }, { "descriptor": "Sulfhydryl Compounds", "descriptor_ui": "D013438", "major_topic": false }, { "descriptor": "Time Factors", "descriptor_ui": "D013997", "major_topic": false } ], "publication": { "conference_name": null, "date": "2012", "date_precision": "year", "issue": "8", "normalized_date": "2012", "pages": "e44283", "proceedings_title": null, "publisher": "", "title": "PloS one", "volume": "7", "year": 2012 }, "ssbd": { "database": [], "repository": [] }, "title": "A yeast metabolite extraction protocol optimised for time-series analyses.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Lung cancer research has recently made significant progress in understanding the molecular pathogenesis of lung cancer and in developing treatments for it. Such achievements are directly utilized in clinical practice. Indeed, the echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase (ALK) fusion gene was first described in non-small cell lung cancer in 2007, and a molecularly targeted drug against the fusion was approved in 2011. However, lung cancer with the ALK fusion constitutes only a small fraction of lung cancers; therefore, efficient patient selection is crucial for successful treatment using the ALK inhibitor. Currently, RT-PCR, fluorescent in situ hybridization (FISH), and immunohistochemistry are commonly used to detect the ALK fusion. Although FISH is currently the gold standard technique, there are no perfect methods for detecting these genetic alterations. In this article, we discuss the advantages and disadvantages of each method and the possible criteria for selecting patients who are more likely to have the ALK fusion. If we can successfully screen patients, then ALK inhibitor treatment will be the best example of personalized therapy in terms of selecting patients with an uncommon genotype from a larger group with the same tumor phenotype. In other words, the personalized therapy may offer a new challenge for current clinical oncology.", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yoshiko", "last_name": "Murakami", "name": null }, { "creator_type": "author", "first_name": "Tetsuya", "last_name": "Mitsudomi", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null } ], "identifiers": { "doi": { "normalized": "10.3389/fonc.2012.00024" }, "pmcid": { "normalized": "PMC3356052" }, "pmid": { "normalized": "22655265" } }, "mesh": [], "publication": { "conference_name": null, "date": "2012", "date_precision": "year", "issue": "", "normalized_date": "2012", "pages": "24", "proceedings_title": null, "publisher": "", "title": "Frontiers in oncology", "volume": "2", "year": 2012 }, "ssbd": { "database": [], "repository": [] }, "title": "A Screening Method for the ALK Fusion Gene in NSCLC.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Accurate identification of cell nuclei and their tracking using three dimensional (3D) microscopic images is a demanding task in many biological studies. Manual identification of nuclei centroids from images is an error-prone task, sometimes impossible to accomplish due to low contrast and the presence of noise. Nonetheless, only a few methods are available for 3D bioimaging applications, which sharply contrast with 2D analysis, where many methods already exist. In addition, most methods essentially adopt segmentation for which a reliable solution is still unknown, especially for 3D bio-images having juxtaposed cells. In this work, we propose a new method that can directly extract nuclei centroids from fluorescence microscopy images. This method involves three steps: (i) Pre-processing, (ii) Local enhancement, and (iii) Centroid extraction. The first step includes two variations: first variation (Variant-1) uses the whole 3D pre-processed image, whereas the second one (Variant-2) modifies the preprocessed image to the candidate regions or the candidate hybrid image for further processing. At the second step, a multiscale cube filtering is employed in order to locally enhance the pre-processed image. Centroid extraction in the third step consists of three stages. In Stage-1, we compute a local characteristic ratio at every voxel and extract local maxima regions as candidate centroids using a ratio threshold. Stage-2 processing removes spurious centroids from Stage-1 results by analyzing shapes of intensity profiles from the enhanced image. An iterative procedure based on the nearest neighborhood principle is then proposed to combine if there are fragmented nuclei. Both qualitative and quantitative analyses on a set of 100 images of 3D mouse embryo are performed. Investigations reveal a promising achievement of the technique presented in terms of average sensitivity and precision (i.e., 88.04% and 91.30% for Variant-1; 86.19% and 95.00% for Variant-2), when compared with an existing method (86.06% and 90.11%), originally developed for analyzing C. elegans images.", "classifications": [ { "id": "Kobayashi", "label": "Group Kobayashi", "parent": "Wakamoto", "type": "group" }, { "id": "Wakamoto", "label": "Team Wakamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Md Khayrul", "last_name": "Bashar", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Komatsu", "name": null }, { "creator_type": "author", "first_name": "Toshihiko", "last_name": "Fujimori", "name": null }, { "creator_type": "author", "first_name": "Tetsuya J.", "last_name": "Kobayashi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1371/journal.pone.0035550" }, "pmcid": { "normalized": "PMC3348125" }, "pmid": { "normalized": "22590505" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Nucleus", "descriptor_ui": "D002467", "major_topic": true }, { "descriptor": "Embryo, Mammalian", "descriptor_ui": "D004622", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Microscopy, Fluorescence", "descriptor_ui": "D008856", "major_topic": false } ], "publication": { "conference_name": null, "date": "2012", "date_precision": "year", "issue": "5", "normalized_date": "2012", "pages": "e35550", "proceedings_title": null, "publisher": "", "title": "PloS one", "volume": "7", "year": 2012 }, "ssbd": { "database": [ "ssbd-database-000008" ], "repository": [ "ssbd-repos-000008" ] }, "title": "Automatic extraction of nuclei centroids of mouse embryonic cells from fluorescence microscopy images.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "In the two-cell stage embryos of Caenorhabditis elegans, the contact surface of the two blastomeres forms a curve that bulges from the AB blastomere to the P1 blastomere. This curve is a consequence of the high intracellular hydrostatic pressure of AB compared with that of P1. However, the higher pressure in AB is intriguing because AB has a larger volume than P1. In soap bubbles, which are a widely used model of cell shape, a larger bubble has lower pressure than a smaller bubble. Here, we reveal that the higher pressure in AB is mediated by its higher cortical tension. The cell fusion experiments confirmed that the curvature of the contact surface is related to the pressure difference between the cells. Chemical and genetic interferences showed that the pressure difference is mediated by actomyosin. Fluorescence imaging indicated that non-muscle myosin is enriched in the AB cortex. The cell killing experiments provided evidence that AB but not P1 is responsible for the pressure difference. Computer simulation clarified that the cell-to-cell heterogeneity of cortical tensions is indispensable for explaining the pressure difference. This study demonstrates that heterogeneity in surface tension results in significant deviations of cell behavior compared to simple soap bubble models, and thus must be taken into consideration in understanding cell shape within embryos.", "classifications": [ { "id": "Onami", "label": "Group Onami", "parent": "Fujiwara", "type": "group" }, { "id": "Fujiwara", "label": "Team Fujiwara", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Masashi", "last_name": "Fujita", "name": null }, { "creator_type": "author", "first_name": "Shuichi", "last_name": "Onami", "name": null } ], "identifiers": { "doi": { "normalized": "10.1371/journal.pone.0030224" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "22253922" } }, "mesh": [ { "descriptor": "Actin Cytoskeleton", "descriptor_ui": "D008841", "major_topic": false }, { "descriptor": "Actomyosin", "descriptor_ui": "D000205", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Caenorhabditis elegans", "descriptor_ui": "D017173", "major_topic": false }, { "descriptor": "Cell Communication", "descriptor_ui": "D002450", "major_topic": true }, { "descriptor": "Cell Death", "descriptor_ui": "D016923", "major_topic": false }, { "descriptor": "Cell Shape", "descriptor_ui": "D048430", "major_topic": false }, { "descriptor": "Cell Size", "descriptor_ui": "D048429", "major_topic": false }, { "descriptor": "Computer Simulation", "descriptor_ui": "D003198", "major_topic": false }, { "descriptor": "Cytoplasm", "descriptor_ui": "D003593", "major_topic": false }, { "descriptor": "Embryo, Nonmammalian", "descriptor_ui": "D004625", "major_topic": false }, { "descriptor": "Extracellular Space", "descriptor_ui": "D005110", "major_topic": false }, { "descriptor": "Lasers", "descriptor_ui": "D007834", "major_topic": false }, { "descriptor": "Models, Biological", "descriptor_ui": "D008954", "major_topic": false }, { "descriptor": "Muscles", "descriptor_ui": "D009132", "major_topic": false }, { "descriptor": "Pressure", "descriptor_ui": "D011312", "major_topic": false }, { "descriptor": "Surface Tension", "descriptor_ui": "D013500", "major_topic": false }, { "descriptor": "Ultraviolet Rays", "descriptor_ui": "D014466", "major_topic": false } ], "publication": { "conference_name": null, "date": "2012", "date_precision": "year", "issue": "1", "normalized_date": "2012", "pages": "", "proceedings_title": null, "publisher": "", "title": "PLoS ONE", "volume": "7", "year": 2012 }, "ssbd": { "database": [], "repository": [] }, "title": "Cell-to-Cell Heterogeneity in Cortical Tension Specifies Curvature of Contact Surfaces in Caenorhabditis elegans Embryos.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Encystation, which is cellular differentiation from the motile, proliferative, labile trophozoite form to the dormant, resistant cyst form, is a crucial process found in parasitic and free-living protozoa such as Entamoeba, Giardia, Acanthamoeba, and Balamuthia. Since encystation is an essential process to deal with the adverse external environmental changes during the life cycle, and often integral to the transmission of the diseases, biochemical understanding of the process potentially provides useful measures against the infections caused by this group of protozoa. In this study, we investigated metabolic and transcriptomic changes that occur during encystation in Entamoeba invadens, the reptilian sibling of mammal-infecting E. histolytica, using capillary electrophoresis-tandem mass spectrometry-based metabolite profiling and DNA microarray-based expression profiling. As the encystation progressed, the levels of majority of metabolites involved in glycolysis and nucleotides drastically decreased, indicating energy generation is ceased. Furthermore, the flux of glycolysis was redirected toward chitin wall biosynthesis. We found remarkable temporal increases in biogenic amines such as isoamylamine, isobutylamine, and cadaverine, during the early period of encystation, when the trophozoites form large multicellular aggregates (precyst). We also found remarkable induction of γ-aminobutyric acid (GABA) during encystation. This study has unveiled for the first time the dynamics of the transcriptional and metabolic regulatory networks during encystation, and should help in better understanding of the process in pathogenic eukaryotes, and further development of measures controlling infections they cause.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Ghulam", "last_name": "Jeelani", "name": null }, { "creator_type": "author", "first_name": "Dan", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Afzal", "last_name": "Husain", "name": null }, { "creator_type": "author", "first_name": "Aleyla", "last_name": "Escueta-de Cadiz", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Sugimoto", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Suematsu", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Nozaki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1371/journal.pone.0037740" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "22662204" } }, "mesh": [ { "descriptor": "Amino Acids", "descriptor_ui": "D000596", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Chitin", "descriptor_ui": "D002686", "major_topic": false }, { "descriptor": "Cluster Analysis", "descriptor_ui": "D016000", "major_topic": false }, { "descriptor": "Entamoeba", "descriptor_ui": "D004747", "major_topic": false }, { "descriptor": "gamma-Aminobutyric Acid", "descriptor_ui": "D005680", "major_topic": false }, { "descriptor": "Glycolysis", "descriptor_ui": "D006019", "major_topic": false }, { "descriptor": "Metabolic Networks and Pathways", "descriptor_ui": "D053858", "major_topic": false }, { "descriptor": "Metabolome", "descriptor_ui": "D055442", "major_topic": true }, { "descriptor": "Nucleotides", "descriptor_ui": "D009711", "major_topic": false }, { "descriptor": "Polyamines", "descriptor_ui": "D011073", "major_topic": false }, { "descriptor": "Transcriptome", "descriptor_ui": "D059467", "major_topic": false } ], "publication": { "conference_name": null, "date": "2012", "date_precision": "year", "issue": "5", "normalized_date": "2012", "pages": "", "proceedings_title": null, "publisher": "", "title": "PLoS ONE", "volume": "7", "year": 2012 }, "ssbd": { "database": [], "repository": [] }, "title": "Metabolic Profiling of the Protozoan Parasite Entamoeba invadens Revealed Activation of Unpredicted Pathway during Encystation.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "We characterized a recently developed hyperactive piggyBac (pB) transposase enzyme [containing seven mutations (7pB)] for gene transfer in human cells in vitro and to somatic cells in mice in vivo. Despite a protein level expression similar to that of native pB, 7pB significantly increased the gene transfer efficiency of a neomycin resistance cassette transposon in both HEK293 and HeLa cultured human cells. Native pB and SB100X, the most active transposase of the Sleeping Beauty transposon system, exhibited similar transposition efficiency in cultured human cell lines. When delivered to primary human T cells ex vivo, 7pB increased gene delivery two- to threefold compared with piggyBac and SB100X. The activity of hyperactive 7pB transposase was not affected by the addition of a 24-kDa N-terminal tag, whereas SB100X manifested a 50% reduction in transposition. Hyperactive 7pB was compared with native pB and SB100X in vivo in mice using hydrodynamic tail-vein injection of a limiting dose of transposase DNA combined with luciferase reporter transposons. We followed transgene expression for up to 6 months and observed approximately 10-fold greater long-term gene expression in mice injected with a codon-optimized version of 7pB compared with mice injected with native pB or SB100X. We conclude that hyperactive piggyBac elements can increase gene transfer in human cells and in vivo and should enable improved gene delivery using the piggyBac transposon system in a variety of cell and gene-therapy applications.", "classifications": [ { "id": "Yusa", "label": "Group Yusa", "parent": "Eiraku", "type": "group" }, { "id": "Eiraku", "label": "Team Eiraku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Joseph E.", "last_name": "Doherty", "name": null }, { "creator_type": "author", "first_name": "Leslie E.", "last_name": "Huye", "name": null }, { "creator_type": "author", "first_name": "Kosuke", "last_name": "Yusa", "name": null }, { "creator_type": "author", "first_name": "Liqin", "last_name": "Zhou", "name": null }, { "creator_type": "author", "first_name": "Nancy L.", "last_name": "Craig", "name": null }, { "creator_type": "author", "first_name": "Matthew H.", "last_name": "Wilson", "name": null } ], "identifiers": { "doi": { "normalized": "10.1089/hum.2011.138" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "21992617" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "DNA Transposable Elements", "descriptor_ui": "D004251", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Gene Transfer Techniques", "descriptor_ui": "D018014", "major_topic": false }, { "descriptor": "Genetic Vectors", "descriptor_ui": "D005822", "major_topic": false }, { "descriptor": "HEK293 Cells", "descriptor_ui": "D057809", "major_topic": false }, { "descriptor": "HeLa Cells", "descriptor_ui": "D006367", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Transposases", "descriptor_ui": "D019895", "major_topic": false } ], "publication": { "conference_name": null, "date": "2012 Mar", "date_precision": "unknown", "issue": "3", "normalized_date": null, "pages": "311-320", "proceedings_title": null, "publisher": "", "title": "Human Gene Therapy", "volume": "23", "year": 2012 }, "ssbd": { "database": [], "repository": [] }, "title": "Hyperactive piggyBac Gene Transfer in Human Cells and In Vivo.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "", "classifications": [ { "id": "Toyoshima", "label": "Group Toyoshima", "parent": "Toyoshima", "type": "group" }, { "id": "Toyoshima", "label": "Team Toyoshima", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Fumiko", "last_name": "Toyoshima", "name": null } ], "identifiers": { "doi": { "normalized": null }, "pmcid": { "normalized": null }, "pmid": { "normalized": "22550898" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Division", "descriptor_ui": "D002455", "major_topic": false }, { "descriptor": "Fusion Proteins, bcr-abl", "descriptor_ui": "D016044", "major_topic": false }, { "descriptor": "Genome-Wide Association Study", "descriptor_ui": "D055106", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Intestine, Small", "descriptor_ui": "D007421", "major_topic": false }, { "descriptor": "Kidney", "descriptor_ui": "D007668", "major_topic": false }, { "descriptor": "RNA Interference", "descriptor_ui": "D034622", "major_topic": false }, { "descriptor": "Skin", "descriptor_ui": "D012867", "major_topic": false } ], "publication": { "conference_name": null, "date": "2012 Feb", "date_precision": "unknown", "issue": "2", "normalized_date": null, "pages": "81-91", "proceedings_title": null, "publisher": "", "title": "Seikagaku. The Journal of Japanese Biochemical Society", "volume": "84", "year": 2012 }, "ssbd": { "database": [], "repository": [] }, "title": "[Mechanisms for oriented cell division in mammalian cells].", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "We present a formulation of branching and aging processes that allows age distributions along lineages to be studied within populations, and provides a new interpretation of classical results in the theory of aging. We establish a variational principle for the stable age distribution along lineages. Using this optimal lineage principle, we show that the response of a population's growth rate to age-specific changes in mortality and fecundity--a key quantity that was first calculated by Hamilton--is given directly by the age distribution along lineages. We apply our method also to the Bellman-Harris process, in which both mother and progeny are rejuvenated at each reproduction event, and show that this process can be mapped to the classic aging process such that age statistics in the population and along lineages are identical. Our approach provides both a theoretical framework for understanding the statistics of aging in a population, and a new method of analytical calculations for populations with age structure. We discuss generalizations for populations with multiple phenotypes, and more complex aging processes. We also provide a first experimental test of our theory applied to bacterial populations growing in a microfluidics device.", "classifications": [ { "id": "Wakamoto", "label": "Group Wakamoto", "parent": "Wakamoto", "type": "group" }, { "id": "Wakamoto", "label": "Team Wakamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yuichi", "last_name": "Wakamoto", "name": null }, { "creator_type": "author", "first_name": "Alexander Y.", "last_name": "Grosberg", "name": null }, { "creator_type": "author", "first_name": "Edo", "last_name": "Kussell", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/j.1558-5646.2011.01418.x" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "22220869" } }, "mesh": [ { "descriptor": "Aging", "descriptor_ui": "D000375", "major_topic": true }, { "descriptor": "Bacteria", "descriptor_ui": "D001419", "major_topic": false }, { "descriptor": "Biological Evolution", "descriptor_ui": "D005075", "major_topic": false }, { "descriptor": "Cell Proliferation", "descriptor_ui": "D049109", "major_topic": false }, { "descriptor": "Models, Biological", "descriptor_ui": "D008954", "major_topic": true }, { "descriptor": "Population Growth", "descriptor_ui": "D011158", "major_topic": false }, { "descriptor": "Selection, Genetic", "descriptor_ui": "D012641", "major_topic": false } ], "publication": { "conference_name": null, "date": "2012 Jan", "date_precision": "unknown", "issue": "1", "normalized_date": null, "pages": "115-134", "proceedings_title": null, "publisher": "", "title": "Evolution; international journal of organic evolution", "volume": "66", "year": 2012 }, "ssbd": { "database": [], "repository": [] }, "title": "Optimal lineage principle for age-structured populations.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The Mouse Multiple Tissue Metabolome Database (MMMDB) provides comprehensive and quantitative metabolomic information for multiple tissues from single mice. Manually curated databases that integrate literature-based individual metabolite information have been available so far. However, data sets on the absolute concentration of a single metabolite integrated from multiple resources are often difficult to be used when different metabolomic studies are compared because the relative balance of the multiple metabolite concentrations in the metabolic pathways as a snapshot of a dynamic system is more important than the absolute concentration of a single metabolite. We developed MMMDB by performing non-targeted analyses of cerebra, cerebella, thymus, spleen, lung, liver, kidney, heart, pancreas, testis and plasma using capillary electrophoresis time-of-flight mass spectrometry and detected 428 non-redundant features from which 219 metabolites were successfully identified. Quantified concentrations of the individual metabolites and the corresponding processed raw data; for example, the electropherograms and mass spectra with their annotations, such as isotope and fragment information, are stored in the database. MMMDB is designed to normalize users' data, which can be submitted online and used to visualize overlaid electropherograms. Thus, MMMDB allows newly measured data to be compared with the other data in the database. MMMDB is available at: http://mmmdb.iab.keio.ac.jp.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Masahiro", "last_name": "Sugimoto", "name": null }, { "creator_type": "author", "first_name": "Satsuki", "last_name": "Ikeda", "name": null }, { "creator_type": "author", "first_name": "Kanako", "last_name": "Niigata", "name": null }, { "creator_type": "author", "first_name": "Masaru", "last_name": "Tomita", "name": null }, { "creator_type": "author", "first_name": "Hideyo", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null } ], "identifiers": { "doi": { "normalized": "10.1093/nar/gkr1170" }, "pmcid": { "normalized": "PMC3245187" }, "pmid": { "normalized": "22139941" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Databases, Factual", "descriptor_ui": "D016208", "major_topic": true }, { "descriptor": "Electrophoresis, Capillary", "descriptor_ui": "D019075", "major_topic": false }, { "descriptor": "Internet", "descriptor_ui": "D020407", "major_topic": false }, { "descriptor": "Mass Spectrometry", "descriptor_ui": "D013058", "major_topic": false }, { "descriptor": "Metabolome", "descriptor_ui": "D055442", "major_topic": true }, { "descriptor": "Metabolomics", "descriptor_ui": "D055432", "major_topic": true }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false } ], "publication": { "conference_name": null, "date": "2012 Jan", "date_precision": "unknown", "issue": "Database issue", "normalized_date": null, "pages": "D809-814", "proceedings_title": null, "publisher": "", "title": "Nucleic acids research", "volume": "40", "year": 2012 }, "ssbd": { "database": [], "repository": [] }, "title": "MMMDB: Mouse Multiple Tissue Metabolome Database.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Neurons develop dendritic arbors in cell type-specific patterns. Using growing Purkinje cells in culture as a model, we performed a long-term time-lapse observation of dendrite branch dynamics to understand the rules that govern the characteristic space-filling dendrites. We found that dendrite architecture was sculpted by a combination of reproducible dynamic processes, including constant tip elongation, stochastic terminal branching, and retraction triggered by contacts between growing dendrites. Inhibition of protein kinase C/protein kinase D signaling prevented branch retraction and significantly altered the characteristic morphology of long proximal segments. A computer simulation of dendrite branch dynamics using simple parameters from experimental measurements reproduced the time-dependent changes in the dendrite configuration in live Purkinje cells. Furthermore, perturbation analysis to parameters in silico validated the important contribution of dendritic retraction in the formation of the characteristic morphology. We present an approach using live imaging and computer simulations to clarify the fundamental mechanisms of dendrite patterning in the developing brain.", "classifications": [ { "id": "Mochizuki", "label": "Group Mochizuki", "parent": "Eiraku", "type": "group" }, { "id": "Eiraku", "label": "Team Eiraku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Kazuto", "last_name": "Fujishima", "name": null }, { "creator_type": "author", "first_name": "Ryota", "last_name": "Horie", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Mochizuki", "name": null }, { "creator_type": "author", "first_name": "Mineko", "last_name": "Kengaku", "name": null } ], "identifiers": { "doi": { "normalized": "10.1242/dev.081315" }, "pmcid": { "normalized": "PMC3491647" }, "pmid": { "normalized": "22912417" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cerebellum", "descriptor_ui": "D002531", "major_topic": false }, { "descriptor": "Computer Simulation", "descriptor_ui": "D003198", "major_topic": false }, { "descriptor": "Dendrites", "descriptor_ui": "D003712", "major_topic": false }, { "descriptor": "Immunohistochemistry", "descriptor_ui": "D007150", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Purkinje Cells", "descriptor_ui": "D011689", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Time-Lapse Imaging", "descriptor_ui": "D059008", "major_topic": false } ], "publication": { "conference_name": null, "date": "2012 Sep", "date_precision": "unknown", "issue": "18", "normalized_date": null, "pages": "3442-3455", "proceedings_title": null, "publisher": "", "title": "Development (Cambridge, England)", "volume": "139", "year": 2012 }, "ssbd": { "database": [], "repository": [] }, "title": "Principles of branch dynamics governing shape characteristics of cerebellar Purkinje cell dendrites.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Patterning during organogenesis is fundamentally realized through the interpretation of morphogen gradients by particular types of gene regulatory networks (GRNs). However, as quantitative studies have reported, spatial profiles of morphogen gradients include intra-embryo and inter-embryo variability, which could lead to errors in spatial recognition by cells and variations in patterning. By mathematically modeling the processes of generation and readout of spatial information - information encoding and decoding, by an analogy to computer communication - and maximizing the reproducibility of patterning against noise, the general designs of gradient profiles and their interpretation have been clarified. Furthermore, over the past few years, basic studies on patterning in more dynamic situations, that is, patterning in growing tissues with time-variant gradients, have been initiated. Here we provide an overview of patterning studies, pattern generating GRNs, concepts of information coding design for robust patterning, and patterning in growing tissues.", "classifications": [ { "id": "Morishita", "label": "Group Morishita", "parent": "Morishita", "type": "group" }, { "id": "Morishita", "label": "Team Morishita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Ken-ichi", "last_name": "Hironaka", "name": null }, { "creator_type": "author", "first_name": "Yoshihiro", "last_name": "Morishita", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.gde.2012.10.002" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "23200115" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Body Patterning", "descriptor_ui": "D019521", "major_topic": false }, { "descriptor": "Drosophila melanogaster", "descriptor_ui": "D004331", "major_topic": false }, { "descriptor": "Gene Expression Regulation, Developmental", "descriptor_ui": "D018507", "major_topic": false }, { "descriptor": "Gene Regulatory Networks", "descriptor_ui": "D053263", "major_topic": false }, { "descriptor": "Models, Biological", "descriptor_ui": "D008954", "major_topic": false }, { "descriptor": "Models, Theoretical", "descriptor_ui": "D008962", "major_topic": true }, { "descriptor": "Organogenesis", "descriptor_ui": "D038081", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false } ], "publication": { "conference_name": null, "date": "2012 Dec", "date_precision": "unknown", "issue": "6", "normalized_date": null, "pages": "553-561", "proceedings_title": null, "publisher": "", "title": "Current opinion in genetics & development", "volume": "22", "year": 2012 }, "ssbd": { "database": [], "repository": [] }, "title": "Encoding and decoding of positional information in morphogen-dependent patterning.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Although mammalian neurogenesis is mostly completed by the perinatal period, new neurons are continuously generated throughout adulthood in the restricted regions of the brain. Newly generated neurons are incorporated into the neural networks of both the hippocampal dentate gyrus and the olfactory bulb, and there is growing evidence that adult neurogenesis is important for various brain functions. Continuous neurogenesis is achieved by the coordinated proliferation and differentiation of adult neural stem cells. In this review, we discuss the recent findings concerning the roles of Notch signaling and Hes-family genes in adult neural stem cells. We also discuss the recent findings about the integration mode of new neurons into the existing neural circuits and the potential significance of adult neurogenesis in higher brain functions, such as spatial and olfactory memory.", "classifications": [ { "id": "Imayoshi", "label": "Group Imayoshi", "parent": "Imayoshi", "type": "group" }, { "id": "Imayoshi", "label": "Team Imayoshi", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Itaru", "last_name": "Imayoshi", "name": null } ], "identifiers": { "doi": { "normalized": null }, "pmcid": { "normalized": null }, "pmid": { "normalized": "23373318" } }, "mesh": [ { "descriptor": "Aging", "descriptor_ui": "D000375", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Brain", "descriptor_ui": "D001921", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Neural Stem Cells", "descriptor_ui": "D058953", "major_topic": false }, { "descriptor": "Neurogenesis", "descriptor_ui": "D055495", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false } ], "publication": { "conference_name": null, "date": "2012 Nov", "date_precision": "unknown", "issue": "5-6", "normalized_date": null, "pages": "293-297", "proceedings_title": null, "publisher": "", "title": "Nihon shinkei seishin yakurigaku zasshi = Japanese journal of psychopharmacology", "volume": "32", "year": 2012 }, "ssbd": { "database": [], "repository": [] }, "title": "[Neurogenesis in the postnatal and adult brain].", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Reporters of Cre and/or Flp activity are important for defining the spatial and temporal extent of Cre/Flp-mediated recombination. Here, we describe R26-CAG-LF-mTFP1, a multifunctional fluorescent reporter mouse that strongly expresses mTFP1 (bright teal fluorescent protein) after Cre- and Flp-mediated recombination. To meet the need for single recombinase-mediated reporter expression, we generated derivatives of R26-CAG-LF-mTFP1. The germline excision of the Frt-flanked stop cassette in R26-CAG-LF-mTFP1 generated a Cre-dependent reporter (R26-CAG-LoxP-mTFP1). Similarly, R26-CAG-FRT-mTFP1, in which the loxP-flanked stop cassette was excised in the germline, requires only Flp to activate mTFP1 expression.", "classifications": [ { "id": "Imayoshi", "label": "Group Imayoshi", "parent": "Imayoshi", "type": "group" }, { "id": "Imayoshi", "label": "Team Imayoshi", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Itaru", "last_name": "Imayoshi", "name": null }, { "creator_type": "author", "first_name": "Kyoko", "last_name": "Hirano", "name": null }, { "creator_type": "author", "first_name": "Masayuki", "last_name": "Sakamoto", "name": null }, { "creator_type": "author", "first_name": "Goichi", "last_name": "Miyoshi", "name": null }, { "creator_type": "author", "first_name": "Tetsuya", "last_name": "Imura", "name": null }, { "creator_type": "author", "first_name": "Satsuki", "last_name": "Kitano", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Miyachi", "name": null }, { "creator_type": "author", "first_name": "Ryoichiro", "last_name": "Kageyama", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.neures.2012.02.003" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "22343123" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "DNA Nucleotidyltransferases", "descriptor_ui": "D004254", "major_topic": false }, { "descriptor": "Gene Knock-In Techniques", "descriptor_ui": "D055879", "major_topic": false }, { "descriptor": "Genes, Reporter", "descriptor_ui": "D017930", "major_topic": false }, { "descriptor": "Green Fluorescent Proteins", "descriptor_ui": "D049452", "major_topic": false }, { "descriptor": "Integrases", "descriptor_ui": "D019426", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Transgenic", "descriptor_ui": "D008822", "major_topic": false }, { "descriptor": "Proteins", "descriptor_ui": "D011506", "major_topic": false }, { "descriptor": "Recombination, Genetic", "descriptor_ui": "D011995", "major_topic": false }, { "descriptor": "RNA, Untranslated", "descriptor_ui": "D022661", "major_topic": false } ], "publication": { "conference_name": null, "date": "2012 May", "date_precision": "unknown", "issue": "1", "normalized_date": null, "pages": "85-91", "proceedings_title": null, "publisher": "", "title": "Neuroscience research", "volume": "73", "year": 2012 }, "ssbd": { "database": [], "repository": [] }, "title": "A multifunctional teal-fluorescent Rosa26 reporter mouse line for Cre- and Flp-mediated recombination.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Biological systems are increasingly being studied in a holistic manner, using omics approaches, to provide quantitative and qualitative descriptions of the diverse collection of cellular components. Among the omics approaches, metabolomics, which deals with the quantitative global profiling of small molecules or metabolites, is being used extensively to explore the dynamic response of living systems, such as organelles, cells, tissues, organs and whole organisms, under diverse physiological and pathological conditions. This technology is now used routinely in a number of applications, including basic and clinical research, agriculture, microbiology, food science, nutrition, pharmaceutical research, environmental science and the development of biofuels. Of the multiple analytical platforms available to perform such analyses, nuclear magnetic resonance and mass spectrometry have come to dominate, owing to the high resolution and large datasets that can be generated with these techniques. The large multidimensional datasets that result from such studies must be processed and analyzed to render this data meaningful. Thus, bioinformatics tools are essential for the efficient processing of huge datasets, the characterization of the detected signals, and to align multiple datasets and their features. This paper provides a state-of-the-art overview of the data processing tools available, and reviews a collection of recent reports on the topic. Data conversion, pre-processing, alignment, normalization and statistical analysis are introduced, with their advantages and disadvantages, and comparisons are made to guide the reader.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Masahiro", "last_name": "Sugimoto", "name": null }, { "creator_type": "author", "first_name": "Masato", "last_name": "Kawakami", "name": null }, { "creator_type": "author", "first_name": "Martin", "last_name": "Robert", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Masaru", "last_name": "Tomita", "name": null } ], "identifiers": { "doi": { "normalized": "10.2174/157489312799304431" }, "pmcid": { "normalized": "PMC3299976" }, "pmid": { "normalized": "22438836" } }, "mesh": [], "publication": { "conference_name": null, "date": "2012 Mar", "date_precision": "unknown", "issue": "1", "normalized_date": null, "pages": "96-108", "proceedings_title": null, "publisher": "", "title": "Current bioinformatics", "volume": "7", "year": 2012 }, "ssbd": { "database": [], "repository": [] }, "title": "Bioinformatics Tools for Mass Spectroscopy-Based Metabolomic Data Processing and Analysis.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The overexpression of mitochondrial transcription factor A (TFAM) attenuates the decrease in mtDNA copy number after myocardial infarction, ameliorates pathological hypertrophy, and markedly improves survival. However, non-transgenic strategy to increase mtDNA for the treatment of pathological hypertrophy remains unknown. We produced recombinant human TFAM protein (rhTFAM). rhTFAM rapidly entered into mitochondria of cultured cardiac myocytes. rhTFAM increased mtDNA and abolished the activation of nuclear factor of activated T cells (NFAT), which is well known to activate pathological hypertrophy. rhTFAM attenuated subsequent morphological hypertrophy of myocytes as well. rhTFAM would be an attractive molecule in attenuating cardiac pathological hypertrophy.", "classifications": [ { "id": "Nishida", "label": "Group Nishida", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Takeo", "last_name": "Fujino", "name": null }, { "creator_type": "author", "first_name": "Tomomi", "last_name": "Ide", "name": null }, { "creator_type": "author", "first_name": "Masayoshi", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Ken", "last_name": "Onitsuka", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Yuko", "last_name": "Hata", "name": null }, { "creator_type": "author", "first_name": "Motohiro", "last_name": "Nishida", "name": null }, { "creator_type": "author", "first_name": "Takako", "last_name": "Takehara", "name": null }, { "creator_type": "author", "first_name": "Takaaki", "last_name": "Kanemaru", "name": null }, { "creator_type": "author", "first_name": "Naoyuki", "last_name": "Kitajima", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Takazaki", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Kurose", "name": null }, { "creator_type": "author", "first_name": "Dongchon", "last_name": "Kang", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Sunagawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.mito.2012.06.002" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "22709542" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "DNA-Binding Proteins", "descriptor_ui": "D004268", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Hypertrophy", "descriptor_ui": "D006984", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mitochondrial Proteins", "descriptor_ui": "D024101", "major_topic": false }, { "descriptor": "Myocytes, Cardiac", "descriptor_ui": "D032383", "major_topic": false }, { "descriptor": "NFATC Transcription Factors", "descriptor_ui": "D050778", "major_topic": false }, { "descriptor": "Recombinant Proteins", "descriptor_ui": "D011994", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": true }, { "descriptor": "Transcription Factors", "descriptor_ui": "D014157", "major_topic": false } ], "publication": { "conference_name": null, "date": "2012 Jul", "date_precision": "unknown", "issue": "4", "normalized_date": null, "pages": "449-458", "proceedings_title": null, "publisher": "", "title": "Mitochondrion", "volume": "12", "year": 2012 }, "ssbd": { "database": [], "repository": [] }, "title": "Recombinant mitochondrial transcription factor A protein inhibits nuclear factor of activated T cells signaling and attenuates pathological hypertrophy of cardiac myocytes.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "An emerging aspect of redox signaling is the pathway mediated by electrophilic byproducts, such as nitrated cyclic nucleotide (for example, 8-nitroguanosine 3',5'-cyclic monophosphate (8-nitro-cGMP)) and nitro or keto derivatives of unsaturated fatty acids, generated via reactions of inflammation-related enzymes, reactive oxygen species, nitric oxide and secondary products. Here we report that enzymatically generated hydrogen sulfide anion (HS(-)) regulates the metabolism and signaling actions of various electrophiles. HS(-) reacts with electrophiles, best represented by 8-nitro-cGMP, via direct sulfhydration and modulates cellular redox signaling. The relevance of this reaction is reinforced by the significant 8-nitro-cGMP formation in mouse cardiac tissue after myocardial infarction that is modulated by alterations in HS(-) biosynthesis. Cardiac HS(-), in turn, suppresses electrophile-mediated H-Ras activation and cardiac cell senescence, contributing to the beneficial effects of HS(-) on myocardial infarction-associated heart failure. Thus, this study reveals HS(-)-induced electrophile sulfhydration as a unique mechanism for regulating electrophile-mediated redox signaling.", "classifications": [ { "id": "Akaike", "label": "Group Akaike", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Group Nishida", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Motohiro", "last_name": "Nishida", "name": null }, { "creator_type": "author", "first_name": "Tomohiro", "last_name": "Sawa", "name": null }, { "creator_type": "author", "first_name": "Naoyuki", "last_name": "Kitajima", "name": null }, { "creator_type": "author", "first_name": "Katsuhiko", "last_name": "Ono", "name": null }, { "creator_type": "author", "first_name": "Hirofumi", "last_name": "Inoue", "name": null }, { "creator_type": "author", "first_name": "Hideshi", "last_name": "Ihara", "name": null }, { "creator_type": "author", "first_name": "Hozumi", "last_name": "Motohashi", "name": null }, { "creator_type": "author", "first_name": "Masayuki", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Suematsu", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Kurose", "name": null }, { "creator_type": "author", "first_name": "Albert", "last_name": "van der Vliet", "name": null }, { "creator_type": "author", "first_name": "Bruce A.", "last_name": "Freeman", "name": null }, { "creator_type": "author", "first_name": "Takahiro", "last_name": "Shibata", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Uchida", "name": null }, { "creator_type": "author", "first_name": "Yoshito", "last_name": "Kumagai", "name": null }, { "creator_type": "author", "first_name": "Takaaki", "last_name": "Akaike", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/nchembio.1018" }, "pmcid": { "normalized": "PMC4123552" }, "pmid": { "normalized": "22772154" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Anions", "descriptor_ui": "D000838", "major_topic": false }, { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "Cell Membrane", "descriptor_ui": "D002462", "major_topic": false }, { "descriptor": "Cyclic GMP", "descriptor_ui": "D006152", "major_topic": false }, { "descriptor": "Gene Expression Regulation", "descriptor_ui": "D005786", "major_topic": false }, { "descriptor": "Genes, ras", "descriptor_ui": "D011905", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Hydrogen Sulfide", "descriptor_ui": "D006862", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Molecular Structure", "descriptor_ui": "D015394", "major_topic": false }, { "descriptor": "Myocytes, Cardiac", "descriptor_ui": "D032383", "major_topic": false }, { "descriptor": "Oxidation-Reduction", "descriptor_ui": "D010084", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "RNA Interference", "descriptor_ui": "D034622", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false } ], "publication": { "conference_name": null, "date": "2012 Aug", "date_precision": "unknown", "issue": "8", "normalized_date": null, "pages": "714-724", "proceedings_title": null, "publisher": "", "title": "Nature chemical biology", "volume": "8", "year": 2012 }, "ssbd": { "database": [], "repository": [] }, "title": "Hydrogen sulfide anion regulates redox signaling via electrophile sulfhydration.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Body mass index (BMI) is an independent risk factor for luminal-type breast cancer in Western populations. However, it is unclear whether the impact of BMI differs according to breast cancer subtype in Japanese populations. We conducted a case-control study with 715 cases and 1430 age- and menopausal status-matched controls to evaluate the associations of BMI and its change (from age 20 years to the current age) with breast cancer risk. We applied conditional logistic regression models to estimate odds ratios (ORs) and 95% confidence intervals (CIs). Tumor subtypes were divided into four subtypes, namely the luminal, luminal/HER2, HER2-rich, and triple-negative subtypes. Current BMI and BMI change were positively associated with postmenopausal breast cancer risk. On stratified analysis by tumor subtype, we observed associations between current BMI and BMI change and postmenopausal breast cancer risk for the luminal subtype, with OR for each 1 kg/m(2) increase in current BMI of 1.14 (95% CI: 1.07 - 1.20) and the corresponding OR of BMI change of 1.16 (1.09 - 1.23) (each P(trend) < 0.001). Additionally, we found the same tendency for the triple-negative subtype, with the OR for a 1 kg/m(2) increase in current BMI of 1.21 (1.05 - 1.39) and that for BMI change of 1.18 (1.02 - 1.36) (P(trend) was 0.008 and 0.024, respectively). In premenopausal women, a suggestive inverse association was observed between BMI change and breast cancer risk for the luminal subtype only, with OR of BMI change of 0.93 (0.87 - 1.00, P(trend) = 0.054). No association was seen between BMI at age 20 years and risk of any tumor subtype. In conclusion, BMI and its change are associated with the risk of both luminal and triple-negative breast cancer among postmenopausal Japanese women. These findings suggest the etiological heterogeneity of breast cancer among tumor subtypes. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/2193-1801-1-39) contains supplementary material, which is available to authorized users.", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Aiko", "last_name": "Sueta", "name": null }, { "creator_type": "author", "first_name": "Hidemi", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Tania", "last_name": "Islam", "name": null }, { "creator_type": "author", "first_name": "Satoyo", "last_name": "Hosono", "name": null }, { "creator_type": "author", "first_name": "Miki", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Kaoru", "last_name": "Hirose", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Fujita", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null }, { "creator_type": "author", "first_name": "Hiroji", "last_name": "Iwata", "name": null }, { "creator_type": "author", "first_name": "Kazuo", "last_name": "Tajima", "name": null }, { "creator_type": "author", "first_name": "Hideo", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Hirotaka", "last_name": "Iwase", "name": null }, { "creator_type": "author", "first_name": "Keitaro", "last_name": "Matsuo", "name": null } ], "identifiers": { "doi": { "normalized": "10.1186/2193-1801-1-39" }, "pmcid": { "normalized": "PMC3550694" }, "pmid": { "normalized": "23350064" } }, "mesh": [], "publication": { "conference_name": null, "date": "2012 Dec", "date_precision": "unknown", "issue": "1", "normalized_date": null, "pages": "39", "proceedings_title": null, "publisher": "", "title": "SpringerPlus", "volume": "1", "year": 2012 }, "ssbd": { "database": [], "repository": [] }, "title": "Differential impact of body mass index and its change on the risk of breast cancer by molecular subtype: A case-control study in Japanese women.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "8-Nitro-cGMP is an endogenous nucleotide discovered under inflammation conditions as an important mediator of nitric oxide (NO) signaling. Besides cGMP-like behaviour, 8-nitro-cGMP exerts unique cytoprotective effects against oxidative stress. Although the formation of 8-nitro-cGMP from 8-nitro-GTP has previously been proposed, the mechanism by which excess or unused 8-nitro-cGMP is removed from cells remains unknown. In this study, we report a nitric oxide-dependent cellular conversion of 8-nitro-cGMP to intact cGMP in RAW 264.7 macrophage cells. In our experiments, we synthesized isotopically labeled 8-nitro-cGMP as a tool for metabolites analysis and identified 8-amino-cGMP as an initial metabolite of 8-nitro-cGMP using a LC-MS/MS technique. We also proved that endogenous 8-nitro-cGMP can be converted into 8-amino-cGMP by immunocytochemical staining with an antibody that specifically recognizes 8-amino-cGMP. Moreover, we showed that isotopically labeled 8-amino-cGMP is metabolized into cGMP under inflammation conditions. We propose that nitrosylation of 8-amino-cGMP occurs by NO formation under stress conditions and gives putative 8-diazonium-cGMP, which subsequently decomposes into cGMP. To the best of our knowledge, this study is the first to report reductive deamination of aminoguanine nucleotide at the C-8 position. The findings of this study collectively indicate that NO plays a crucial role not only in the production of 8-nitro-cGMP but also in its elimination under oxidative stress or inflammation.", "classifications": [ { "id": "Akaike", "label": "Group Akaike", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yohei", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Tomohiro", "last_name": "Sawa", "name": null }, { "creator_type": "author", "first_name": "Jun", "last_name": "Yoshitake", "name": null }, { "creator_type": "author", "first_name": "Chiaki", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Shigemoto", "last_name": "Fujii", "name": null }, { "creator_type": "author", "first_name": "Takaaki", "last_name": "Akaike", "name": null }, { "creator_type": "author", "first_name": "Hirokazu", "last_name": "Arimoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1039/c2mb25189b" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "22892818" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "Chromatography, Liquid", "descriptor_ui": "D002853", "major_topic": false }, { "descriptor": "Cyclic GMP", "descriptor_ui": "D006152", "major_topic": false }, { "descriptor": "Homeostasis", "descriptor_ui": "D006706", "major_topic": false }, { "descriptor": "Immunohistochemistry", "descriptor_ui": "D007150", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Nitric Oxide", "descriptor_ui": "D009569", "major_topic": false }, { "descriptor": "omega-N-Methylarginine", "descriptor_ui": "D019323", "major_topic": false }, { "descriptor": "Tandem Mass Spectrometry", "descriptor_ui": "D053719", "major_topic": false } ], "publication": { "conference_name": null, "date": "2012 Nov", "date_precision": "unknown", "issue": "11", "normalized_date": null, "pages": "2909-2915", "proceedings_title": null, "publisher": "", "title": "Molecular bioSystems", "volume": "8", "year": 2012 }, "ssbd": { "database": [], "repository": [] }, "title": "Nitric oxide promotes recycling of 8-nitro-cGMP, a cytoprotective mediator, into intact cGMP in cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: The mucosal layer of the colon contains metabolism-related fluorophores, such as reduced nicotinamide adenine dinucleotide (NADH), which might have the potential to serve as biomarkers for detecting neoplasia. OBJECTIVE: To examine NADH fluorescence in human colonic adenoma while eliminating the effect of hemoglobin absorption and to develop a novel imaging technique for precise detection of adenomas. DESIGN: Cross-sectional study. PATIENTS AND INTERVENTIONS: A total of 66 endoscopically resected colonic polyps were investigated. After serial acquisition of autofluorescence images between 450 and 490 nm illuminated with dual-wavelength excitation at 365 nm (F(365ex)) and 405 nm (F(405ex)) on cross sections of the samples, ratio images were created by dividing F(365ex) by F(405ex). The excitation-emission wavelength combinations in F(365ex) and F(405ex) were optimized for NADH fluorescence and reference fluorescence. MAIN OUTCOME MEASUREMENTS: The F(365ex)/F(405ex) ratio in the tumorous (T) and normal (N) mucosa. RESULTS: F(365ex)/F(405ex) ratio images showed a 1.81- and 1.12-fold higher signal intensity in the adenomas and hyperplastic polyps, respectively, than in the adjacent normal mucosa. The ratio between signal intensities in tumorous mucosa and normal mucosa in F(365ex)/F(405ex) ratio images for tubular adenomas was significantly higher than that for hyperplastic polyps. The signal intensity in F(365ex)/F(405ex) ratio images was not correlated with the hemoglobin concentration index evaluated by reflection images at 550 nm and 610 nm. Diminutive adenomas (<5 mm) and large adenomas were well discriminated in F(365ex)/F(405ex) ratio images. LIMITATIONS: Ex vivo experiment. CONCLUSIONS: These results suggest that the precise measurement of NADH fluorescence intensity together with eliminating the influence of blood hemoglobin concentration serves as a method for visualizing colonic adenomas and that the dual-wavelength excitation method is a promising technique applicable to endoscopic detection of early colonic adenomas.", "classifications": [ { "id": "Tanaka", "label": "Group Tanaka", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Katsuichi", "last_name": "Imaizumi", "name": null }, { "creator_type": "author", "first_name": "Yoshinori", "last_name": "Harada", "name": null }, { "creator_type": "author", "first_name": "Naoki", "last_name": "Wakabayashi", "name": null }, { "creator_type": "author", "first_name": "Yoshihisa", "last_name": "Yamaoka", "name": null }, { "creator_type": "author", "first_name": "Hideyuki", "last_name": "Konishi", "name": null }, { "creator_type": "author", "first_name": "Ping", "last_name": "Dai", "name": null }, { "creator_type": "author", "first_name": "Hideo", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Tetsuro", "last_name": "Takamatsu", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.gie.2011.08.012" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "22032849" } }, "mesh": [ { "descriptor": "Adenoma", "descriptor_ui": "D000236", "major_topic": false }, { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Aged, 80 and over", "descriptor_ui": "D000369", "major_topic": false }, { "descriptor": "Biomarkers, Tumor", "descriptor_ui": "D014408", "major_topic": false }, { "descriptor": "Colonic Neoplasms", "descriptor_ui": "D003110", "major_topic": false }, { "descriptor": "Colonic Polyps", "descriptor_ui": "D003111", "major_topic": false }, { "descriptor": "Cross-Sectional Studies", "descriptor_ui": "D003430", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Fluorescence", "descriptor_ui": "D005453", "major_topic": false }, { "descriptor": "Hemoglobins", "descriptor_ui": "D006454", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Intestinal Mucosa", "descriptor_ui": "D007413", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "NAD", "descriptor_ui": "D009243", "major_topic": false } ], "publication": { "conference_name": null, "date": "2012 Jan", "date_precision": "unknown", "issue": "1", "normalized_date": null, "pages": "110-117", "proceedings_title": null, "publisher": "", "title": "Gastrointestinal endoscopy", "volume": "75", "year": 2012 }, "ssbd": { "database": [], "repository": [] }, "title": "Dual-wavelength excitation of mucosal autofluorescence for precise detection of diminutive colonic adenomas.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "An efficient synthetic route to optically pure norcantharidin analogue NCA-01, a highly selective inhibitor of protein phosphatase 2B (PP2B; calcineurin), has been developed. The absolute stereochemistry of the enantiomers was determined by X-ray crystallographic analysis. Optically pure NCA derivatives that had various substituents at the C1 position were synthesized in a similar manner. The PP2B-inhibitory activities of NCA-01 and its derivatives were independent of the enantiomeric form. NCA-01 dimethyl ester potently inhibited IL-2 production in Jurkat cells.", "classifications": [ { "id": "Sodeoka", "label": "Group Sodeoka", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Tadashi", "last_name": "Shimizu", "name": null }, { "creator_type": "author", "first_name": "Masato", "last_name": "Iizuka", "name": null }, { "creator_type": "author", "first_name": "Hiroko", "last_name": "Matsukura", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Hashizume", "name": null }, { "creator_type": "author", "first_name": "Mikiko", "last_name": "Sodeoka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/asia.201200077" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "22488808" } }, "mesh": [ { "descriptor": "Binding Sites", "descriptor_ui": "D001665", "major_topic": false }, { "descriptor": "Bridged Bicyclo Compounds, Heterocyclic", "descriptor_ui": "D019086", "major_topic": false }, { "descriptor": "Calcineurin", "descriptor_ui": "D019703", "major_topic": false }, { "descriptor": "Calcineurin Inhibitors", "descriptor_ui": "D065095", "major_topic": true }, { "descriptor": "Cell Survival", "descriptor_ui": "D002470", "major_topic": false }, { "descriptor": "Crystallography, X-Ray", "descriptor_ui": "D018360", "major_topic": false }, { "descriptor": "Enzyme Inhibitors", "descriptor_ui": "D004791", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Interleukin-2", "descriptor_ui": "D007376", "major_topic": false }, { "descriptor": "Jurkat Cells", "descriptor_ui": "D019169", "major_topic": false }, { "descriptor": "Protein Structure, Tertiary", "descriptor_ui": "D017434", "major_topic": false }, { "descriptor": "Stereoisomerism", "descriptor_ui": "D013237", "major_topic": false } ], "publication": { "conference_name": null, "date": "2012 Jun", "date_precision": "unknown", "issue": "6", "normalized_date": null, "pages": "1221-1230", "proceedings_title": null, "publisher": "", "title": "Chemistry, an Asian journal", "volume": "7", "year": 2012 }, "ssbd": { "database": [], "repository": [] }, "title": "Synthesis of optically pure norcantharidin analogue NCA-01, a highly selective protein phosphatase 2B inhibitor, and its derivatives.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "p62/SQSTM1 is a selective substrate of autophagy, and aberrant accumulation of p62 has been observed in various pathological conditions. To understand the roles p62 plays in non-small-cell lung cancer (NSCLC), we carried out immunohistochemical analyses of p62 expression in a cohort of patients with annotated clinicopathological data. As analyses of murine and human hepatocellular carcinomas suggested a correlation between p62 and Nrf2 accumulations, we also examined NRF2 expression in the same cohort. The expression of NRF2 and p62 was examined by immunohistochemical methods in 109 NSCLC cases, which included patients with adenocarcinoma (n = 72), squamous cell carcinoma (n = 31), and large cell carcinoma (n = 6). Accumulation of NRF2 and p62 was detected in 34% and 37% of NSCLC patients, respectively. The accumulations of p62 and NRF2 did not correlate with each other, but both were associated with worse lung cancer-specific survival (P = 0.0003 for NRF2; P = 0.0130 for p62). NRF2 status had an impact on NSCLC prognosis irrespective of histology types, but p62 status did so particularly in adenocarcinoma (P = 0.037). Multivariate analysis indicated that positive immunoreactivities of NRF2 and p62 were both independent factors predicting worse lung cancer-specific survival (P < 0.0001 for NRF2 and P = 0.04 for p62). This study revealed that both NRF2 and p62 are independent prognostic factors for NSCLC. The prognostic impact of p62 status was pronounced in adenocarcinoma patients, suggesting that molecular mechanisms underlying cancer evolution differ between adenocarcinoma and squamous cell carcinoma.", "classifications": [ { "id": "Suzuki", "label": "Group Suzuki", "parent": "Takekawa", "type": "group" }, { "id": "Takekawa", "label": "Team Takekawa", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Daisuke", "last_name": "Inoue", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Yoichiro", "last_name": "Mitsuishi", "name": null }, { "creator_type": "author", "first_name": "Yasuhiro", "last_name": "Miki", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Shunichi", "last_name": "Sugawara", "name": null }, { "creator_type": "author", "first_name": "Mika", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Akira", "last_name": "Sakurada", "name": null }, { "creator_type": "author", "first_name": "Chiaki", "last_name": "Endo", "name": null }, { "creator_type": "author", "first_name": "Akira", "last_name": "Uruno", "name": null }, { "creator_type": "author", "first_name": "Hironobu", "last_name": "Sasano", "name": null }, { "creator_type": "author", "first_name": "Takayuki", "last_name": "Nakagawa", "name": null }, { "creator_type": "author", "first_name": "Kennichi", "last_name": "Satoh", "name": null }, { "creator_type": "author", "first_name": "Nobuyuki", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Kubo", "name": null }, { "creator_type": "author", "first_name": "Hozumi", "last_name": "Motohashi", "name": null }, { "creator_type": "author", "first_name": "Masayuki", "last_name": "Yamamoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/j.1349-7006.2012.02216.x" }, "pmcid": { "normalized": "PMC7659245" }, "pmid": { "normalized": "22320446" } }, "mesh": [ { "descriptor": "Adaptor Proteins, Signal Transducing", "descriptor_ui": "D048868", "major_topic": false }, { "descriptor": "Adenocarcinoma", "descriptor_ui": "D000230", "major_topic": false }, { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Carcinoma, Non-Small-Cell Lung", "descriptor_ui": "D002289", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Lung Neoplasms", "descriptor_ui": "D008175", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "NF-E2-Related Factor 2", "descriptor_ui": "D051267", "major_topic": false }, { "descriptor": "Prognosis", "descriptor_ui": "D011379", "major_topic": false }, { "descriptor": "Sequestosome-1 Protein", "descriptor_ui": "D000071456", "major_topic": false } ], "publication": { "conference_name": null, "date": "2012 Apr", "date_precision": "unknown", "issue": "4", "normalized_date": null, "pages": "760-766", "proceedings_title": null, "publisher": "", "title": "Cancer science", "volume": "103", "year": 2012 }, "ssbd": { "database": [], "repository": [] }, "title": "Accumulation of p62/SQSTM1 is associated with poor prognosis in patients with lung adenocarcinoma.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Capillary electrophoresis coupled with time-of-flight mass spectrometry was used to explore new serum biomarkers with high sensitivity and specificity for diabetic nephropathy (DN) diagnosis, through comprehensive analysis of serum metabolites with 78 diabetic patients. Multivariate analyses were used for identification of marker candidates and development of discriminative models. Of the 289 profiled metabolites, orthogonal partial least-squares discriminant analysis identified 19 metabolites that could distinguish between DN with macroalbuminuria and diabetic patients without albuminuria. These identified metabolites included creatinine, aspartic acid, gamma-butyrobetaine, citrulline, symmetric dimethylarginine (SDMA), kynurenine, azelaic acid, and galactaric acid. Significant correlations between all these metabolites and urinary albumin-to-creatinine ratios (p < 0.009, Spearman's rank test) were observed. When five metabolites (including gamma-butyrobetaine, SDMA, azelaic acid and two unknowns) were selected from 19 metabolites and applied for multiple logistic regression model, AUC value for diagnosing DN was 0.927 using the whole dataset, and 0.880 in a cross-validation test. In addition, when four known metabolites (aspartic acid, SDMA, azelaic acid and galactaric acid) were applied, the resulting AUC was still high at 0.844 with the whole dataset and 0.792 with cross-validation. Combination of serum metabolomics with multivariate analyses enabled accurate discrimination of DN patients. The results suggest that capillary electrophoresis-mass spectrometry based metabolome analysis could be used for DN diagnosis.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Akiyoshi", "last_name": "Hirayama", "name": null }, { "creator_type": "author", "first_name": "Eitaro", "last_name": "Nakashima", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Sugimoto", "name": null }, { "creator_type": "author", "first_name": "Shin-ichi", "last_name": "Akiyama", "name": null }, { "creator_type": "author", "first_name": "Waichi", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Shoichi", "last_name": "Maruyama", "name": null }, { "creator_type": "author", "first_name": "Seiichi", "last_name": "Matsuo", "name": null }, { "creator_type": "author", "first_name": "Masaru", "last_name": "Tomita", "name": null }, { "creator_type": "author", "first_name": "Yukio", "last_name": "Yuzawa", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/s00216-012-6412-x" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "23052862" } }, "mesh": [ { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Biomarkers", "descriptor_ui": "D015415", "major_topic": false }, { "descriptor": "Diabetic Nephropathies", "descriptor_ui": "D003928", "major_topic": false }, { "descriptor": "Discriminant Analysis", "descriptor_ui": "D016002", "major_topic": false }, { "descriptor": "Electrophoresis, Capillary", "descriptor_ui": "D019075", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mass Spectrometry", "descriptor_ui": "D013058", "major_topic": false }, { "descriptor": "Metabolome", "descriptor_ui": "D055442", "major_topic": true }, { "descriptor": "Metabolomics", "descriptor_ui": "D055432", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Multivariate Analysis", "descriptor_ui": "D015999", "major_topic": false }, { "descriptor": "ROC Curve", "descriptor_ui": "D012372", "major_topic": false } ], "publication": { "conference_name": null, "date": "2012 Dec", "date_precision": "unknown", "issue": "10", "normalized_date": null, "pages": "3101-3109", "proceedings_title": null, "publisher": "", "title": "Analytical and bioanalytical chemistry", "volume": "404", "year": 2012 }, "ssbd": { "database": [], "repository": [] }, "title": "Metabolic profiling reveals new serum biomarkers for differentiating diabetic nephropathy.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Pyruvate treatment was found to alleviate clinical symptoms of mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome and is highly promising therapeutic. Using capillary electrophoresis time-of-flight mass spectrometry (CE-TOFMS), we measured time-changes of 161 intracellular and 85 medium metabolites to elucidate metabolic effects of pyruvate treatment on cybrid human 143B osteosarcoma cells harboring normal (2SA) and MELAS mutant (2SD) mitochondria. The results demonstrated dramatic and sustainable effects of pyruvate administration on the energy metabolism of 2SD cells, corroborating pyruvate as a metabolically rational treatment regimen for improving symptoms associated with MELAS and possibly other mitochondrial diseases.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Kenjiro", "last_name": "Kami", "name": null }, { "creator_type": "author", "first_name": "Yasunori", "last_name": "Fujita", "name": null }, { "creator_type": "author", "first_name": "Saori", "last_name": "Igarashi", "name": null }, { "creator_type": "author", "first_name": "Sayaka", "last_name": "Koike", "name": null }, { "creator_type": "author", "first_name": "Shoko", "last_name": "Sugawara", "name": null }, { "creator_type": "author", "first_name": "Satsuki", "last_name": "Ikeda", "name": null }, { "creator_type": "author", "first_name": "Naomi", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Masafumi", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Masashi", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Masaru", "last_name": "Tomita", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.mito.2012.07.113" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "22884939" } }, "mesh": [ { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "DNA, Mitochondrial", "descriptor_ui": "D004272", "major_topic": false }, { "descriptor": "Electrophoresis, Capillary", "descriptor_ui": "D019075", "major_topic": false }, { "descriptor": "Energy Metabolism", "descriptor_ui": "D004734", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "MELAS Syndrome", "descriptor_ui": "D017241", "major_topic": false }, { "descriptor": "Metabolome", "descriptor_ui": "D055442", "major_topic": true }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": false }, { "descriptor": "Pyruvic Acid", "descriptor_ui": "D019289", "major_topic": false }, { "descriptor": "Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization", "descriptor_ui": "D019032", "major_topic": false } ], "publication": { "conference_name": null, "date": "2012 Nov", "date_precision": "unknown", "issue": "6", "normalized_date": null, "pages": "644-653", "proceedings_title": null, "publisher": "", "title": "Mitochondrion", "volume": "12", "year": 2012 }, "ssbd": { "database": [], "repository": [] }, "title": "Metabolomic profiling rationalized pyruvate efficacy in cybrid cells harboring MELAS mitochondrial DNA mutations.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "It is well-known that estrogens immensely contribute to the progression of human breast carcinoma, but their detailed molecular mechanisms remain largely unclear. In this study, we identified nucleobindin 2 (NUCB2) as a gene associated with recurrence based on microarray data of estrogen receptor (ER)-positive breast carcinoma cases (n = 10), and subsequent in vitro study showed that NUCB2 expression was upregulated by estradiol in ER-positive MCF-7 cells. However, NUCB2 has not yet been examined in breast carcinoma, and its significance remains unknown. Therefore, we further examined the biological functions of NUCB2 in breast carcinoma using immunohistochemistry and in vitro studies. NUCB2 immunoreactivity was detected in carcinoma cells in 77 of 161 (48%) breast cancer cases, and positively associated with lymph node metastasis and ER status of the patients. In addition, NUCB2 status was significantly associated with an increased risk of recurrence and adverse clinical outcome of the patients using both univariate and multivariate analyses. Results of siRNA transfection experiments showed that NUCB2 significantly increased cell proliferation, and migration and invasion properties in both MCF-7 and ER-negative SK-BR-3 cells. These results suggest that NUCB2 is upregulated by estrogens and plays an important role, especially in the process of metastasis, in breast carcinomas. NUCB2 status is considered a potent prognostic factor in human breast cancer.", "classifications": [ { "id": "Suzuki", "label": "Group Suzuki", "parent": "Takekawa", "type": "group" }, { "id": "Takekawa", "label": "Team Takekawa", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Shiho", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Kiyoshi", "last_name": "Takagi", "name": null }, { "creator_type": "author", "first_name": "Yasuhiro", "last_name": "Miki", "name": null }, { "creator_type": "author", "first_name": "Yoshiaki", "last_name": "Onodera", "name": null }, { "creator_type": "author", "first_name": "Jun-Ichi", "last_name": "Akahira", "name": null }, { "creator_type": "author", "first_name": "Akiko", "last_name": "Ebata", "name": null }, { "creator_type": "author", "first_name": "Takanori", "last_name": "Ishida", "name": null }, { "creator_type": "author", "first_name": "Mika", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Hironobu", "last_name": "Sasano", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Suzuki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/j.1349-7006.2011.02119.x" }, "pmcid": { "normalized": "PMC11164150" }, "pmid": { "normalized": "21988594" } }, "mesh": [ { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Aged, 80 and over", "descriptor_ui": "D000369", "major_topic": false }, { "descriptor": "Biomarkers, Tumor", "descriptor_ui": "D014408", "major_topic": false }, { "descriptor": "Blotting, Western", "descriptor_ui": "D015153", "major_topic": false }, { "descriptor": "Breast Neoplasms", "descriptor_ui": "D001943", "major_topic": false }, { "descriptor": "Calcium-Binding Proteins", "descriptor_ui": "D002135", "major_topic": false }, { "descriptor": "Carcinoma, Ductal, Breast", "descriptor_ui": "D018270", "major_topic": false }, { "descriptor": "Cell Adhesion", "descriptor_ui": "D002448", "major_topic": false }, { "descriptor": "Cell Movement", "descriptor_ui": "D002465", "major_topic": false }, { "descriptor": "Cell Proliferation", "descriptor_ui": "D049109", "major_topic": false }, { "descriptor": "DNA-Binding Proteins", "descriptor_ui": "D004268", "major_topic": false }, { "descriptor": "Estrogens", "descriptor_ui": "D004967", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Follow-Up Studies", "descriptor_ui": "D005500", "major_topic": false }, { "descriptor": "Gene Expression Profiling", "descriptor_ui": "D020869", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Immunoenzyme Techniques", "descriptor_ui": "D007124", "major_topic": false }, { "descriptor": "Laser Capture Microdissection", "descriptor_ui": "D061346", "major_topic": false }, { "descriptor": "Lymphatic Metastasis", "descriptor_ui": "D008207", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Neoplasm Invasiveness", "descriptor_ui": "D009361", "major_topic": false }, { "descriptor": "Neoplasm Recurrence, Local", "descriptor_ui": "D009364", "major_topic": false }, { "descriptor": "Nerve Tissue Proteins", "descriptor_ui": "D009419", "major_topic": false }, { "descriptor": "Nucleobindins", "descriptor_ui": "D000080866", "major_topic": false }, { "descriptor": "Oligonucleotide Array Sequence Analysis", "descriptor_ui": "D020411", "major_topic": false }, { "descriptor": "Prognosis", "descriptor_ui": "D011379", "major_topic": false }, { "descriptor": "Real-Time Polymerase Chain Reaction", "descriptor_ui": "D060888", "major_topic": false }, { "descriptor": "Receptors, Estrogen", "descriptor_ui": "D011960", "major_topic": false }, { "descriptor": "RNA, Messenger", "descriptor_ui": "D012333", "major_topic": false }, { "descriptor": "RNA, Small Interfering", "descriptor_ui": "D034741", "major_topic": false }, { "descriptor": "Survival Rate", "descriptor_ui": "D015996", "major_topic": false }, { "descriptor": "Tumor Cells, Cultured", "descriptor_ui": "D014407", "major_topic": false }, { "descriptor": "Young Adult", "descriptor_ui": "D055815", "major_topic": false } ], "publication": { "conference_name": null, "date": "2012 Jan", "date_precision": "unknown", "issue": "1", "normalized_date": null, "pages": "136-143", "proceedings_title": null, "publisher": "", "title": "Cancer science", "volume": "103", "year": 2012 }, "ssbd": { "database": [], "repository": [] }, "title": "Nucleobindin 2 in human breast carcinoma as a potent prognostic factor.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The neural pathways underlying the respiratory responses elicited by electrical or chemical stimulation of the lateral part of the periaqueductal gray (lPAG) remain unsettled. In the present study, we examined the lPAG projection to neurokinin-1 receptor (NK1R)-immunoreactive (ir) neurons in the ventrolateral medulla (VLM) which have been implicated in the control of respiration. After biotinylated dextranamine (BDA) injection into the lPAG, NK1R-ir neurons in the rostral VLM were embedded in the plexus of BDA-labeled fibers. At the electron microscopic level, the BDA-labeled terminals made asymmetrical synaptic contacts predominantly with dendrites and additionally with somata of the NK1R-ir neurons. Using retrograde tracing combined with in situ hybridization, we demonstrated that the vast majority of the lPAG neurons projecting to the rostral VLM were positive for vesicular glutamate transporter 2 (VGLUT2) mRNA, but not for glutamic acid decarboxylase 67 mRNA. Using a combination of anterograde tracing and immunohistochemistry, we further demonstrated that the lPAG axon terminals with VGLUT2 immunoreactivity made close apposition with the NK1R-ir neuronal profiles in the rostral VLM. These data suggest that lPAG neurons exert an excitatory influence on NK1R-expressing neurons in the rostral VLM for the control of respiration.", "classifications": [ { "id": "Yokota", "label": "Group Yokota", "parent": "Enomoto", "type": "group" }, { "id": "Enomoto", "label": "Team Enomoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Tatsuro", "last_name": "Oka", "name": null }, { "creator_type": "author", "first_name": "Shigefumi", "last_name": "Yokota", "name": null }, { "creator_type": "author", "first_name": "Toshiko", "last_name": "Tsumori", "name": null }, { "creator_type": "author", "first_name": "Jian-Guo", "last_name": "Niu", "name": null }, { "creator_type": "author", "first_name": "Yukihiko", "last_name": "Yasui", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.neures.2012.08.001" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "22921710" } }, "mesh": [ { "descriptor": "Axonal Transport", "descriptor_ui": "D001370", "major_topic": false }, { "descriptor": "Biomarkers", "descriptor_ui": "D015415", "major_topic": false }, { "descriptor": "Biotin", "descriptor_ui": "D001710", "major_topic": false }, { "descriptor": "Dendrites", "descriptor_ui": "D003712", "major_topic": false }, { "descriptor": "Dextrans", "descriptor_ui": "D003911", "major_topic": false }, { "descriptor": "Emotions", "descriptor_ui": "D004644", "major_topic": false }, { "descriptor": "Fluorescent Dyes", "descriptor_ui": "D005456", "major_topic": false }, { "descriptor": "Glutamate Decarboxylase", "descriptor_ui": "D005968", "major_topic": false }, { "descriptor": "Glutamic Acid", "descriptor_ui": "D018698", "major_topic": false }, { "descriptor": "Medulla Oblongata", "descriptor_ui": "D008526", "major_topic": false }, { "descriptor": "Microscopy, Electron", "descriptor_ui": "D008854", "major_topic": false }, { "descriptor": "Nerve Endings", "descriptor_ui": "D009411", "major_topic": false }, { "descriptor": "Nerve Tissue Proteins", "descriptor_ui": "D009419", "major_topic": false }, { "descriptor": "Neural Pathways", "descriptor_ui": "D009434", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Periaqueductal Gray", "descriptor_ui": "D010487", "major_topic": false }, { "descriptor": "Receptors, Neurokinin-1", "descriptor_ui": "D018040", "major_topic": false }, { "descriptor": "Respiratory Center", "descriptor_ui": "D012125", "major_topic": false }, { "descriptor": "RNA, Messenger", "descriptor_ui": "D012333", "major_topic": false }, { "descriptor": "Stilbamidines", "descriptor_ui": "D013266", "major_topic": false }, { "descriptor": "Vesicular Glutamate Transport Protein 2", "descriptor_ui": "D050599", "major_topic": false } ], "publication": { "conference_name": null, "date": "2012 Oct", "date_precision": "unknown", "issue": "2", "normalized_date": null, "pages": "106-115", "proceedings_title": null, "publisher": "", "title": "Neuroscience research", "volume": "74", "year": 2012 }, "ssbd": { "database": [], "repository": [] }, "title": "Glutamatergic neurons in the lateral periaqueductal gray innervate neurokinin-1 receptor-expressing neurons in the ventrolateral medulla of the rat.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Lipids are key components in the viral life cycle that affect host-pathogen interactions. In this study, we investigated the effect of HCV infection on sphingolipid metabolism, especially on endogenous SM levels, and the relationship between HCV replication and endogenous SM molecular species. We demonstrated that HCV induces the expression of the genes (SGMS1 and 2) encoding human SM synthases 1 and 2. We observed associated increases of both total and individual sphingolipid molecular species, as assessed in human hepatocytes and in the detergent-resistant membrane (DRM) fraction in which HCV replicates. SGMS1 expression had a correlation with HCV replication. Inhibition of sphingolipid biosynthesis with a hepatotropic serine palmitoyltransferase (SPT) inhibitor, NA808, suppressed HCV-RNA production while also interfering with sphingolipid metabolism. Further, we identified the SM molecular species that comprise the DRM fraction and demonstrated that these endogenous SM species interacted with HCV nonstructural 5B polymerase to enhance viral replication. Our results reveal that HCV alters sphingolipid metabolism to promote viral replication, providing new insights into the formation of the HCV replication complex and the involvement of host lipids in the HCV life cycle.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yuichi", "last_name": "Hirata", "name": null }, { "creator_type": "author", "first_name": "Kazutaka", "last_name": "Ikeda", "name": null }, { "creator_type": "author", "first_name": "Masayuki", "last_name": "Sudoh", "name": null }, { "creator_type": "author", "first_name": "Yuko", "last_name": "Tokunaga", "name": null }, { "creator_type": "author", "first_name": "Akemi", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Leiyun", "last_name": "Weng", "name": null }, { "creator_type": "author", "first_name": "Masatoshi", "last_name": "Ohta", "name": null }, { "creator_type": "author", "first_name": "Yoshimi", "last_name": "Tobita", "name": null }, { "creator_type": "author", "first_name": "Ken", "last_name": "Okano", "name": null }, { "creator_type": "author", "first_name": "Kazuhisa", "last_name": "Ozeki", "name": null }, { "creator_type": "author", "first_name": "Kenichi", "last_name": "Kawasaki", "name": null }, { "creator_type": "author", "first_name": "Takuo", "last_name": "Tsukuda", "name": null }, { "creator_type": "author", "first_name": "Asao", "last_name": "Katsume", "name": null }, { "creator_type": "author", "first_name": "Yuko", "last_name": "Aoki", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Umehara", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Sekiguchi", "name": null }, { "creator_type": "author", "first_name": "Tetsuya", "last_name": "Toyoda", "name": null }, { "creator_type": "author", "first_name": "Kunitada", "last_name": "Shimotohno", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Nishijima", "name": null }, { "creator_type": "author", "first_name": "Ryo", "last_name": "Taguchi", "name": null }, { "creator_type": "author", "first_name": "Michinori", "last_name": "Kohara", "name": null } ], "identifiers": { "doi": { "normalized": "10.1371/journal.ppat.1002860" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "22916015" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Enzyme Inhibitors", "descriptor_ui": "D004791", "major_topic": false }, { "descriptor": "Gene Expression Regulation, Enzymologic", "descriptor_ui": "D015971", "major_topic": false }, { "descriptor": "Hepacivirus", "descriptor_ui": "D016174", "major_topic": false }, { "descriptor": "Hepatitis C", "descriptor_ui": "D006526", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Membrane Proteins", "descriptor_ui": "D008565", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Nerve Tissue Proteins", "descriptor_ui": "D009419", "major_topic": false }, { "descriptor": "Serine C-Palmitoyltransferase", "descriptor_ui": "D051102", "major_topic": false }, { "descriptor": "Sphingolipids", "descriptor_ui": "D013107", "major_topic": false }, { "descriptor": "Transferases (Other Substituted Phosphate Groups)", "descriptor_ui": "D017855", "major_topic": false }, { "descriptor": "Virus Replication", "descriptor_ui": "D014779", "major_topic": false } ], "publication": { "conference_name": null, "date": "2012 Aug", "date_precision": "unknown", "issue": "8", "normalized_date": null, "pages": "", "proceedings_title": null, "publisher": "", "title": "PLoS Pathogens", "volume": "8", "year": 2012 }, "ssbd": { "database": [], "repository": [] }, "title": "Self-Enhancement of Hepatitis C Virus Replication by Promotion of Specific Sphingolipid Biosynthesis.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "", "classifications": [ { "id": "Nishikii", "label": "Group Nishikii", "parent": "Shintaku", "type": "group" }, { "id": "Shintaku", "label": "Team Shintaku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Makiko", "last_name": "Goto", "name": null }, { "creator_type": "author", "first_name": "Kojiro", "last_name": "Onizawa", "name": null }, { "creator_type": "author", "first_name": "Toru", "last_name": "Yanagawa", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Yamagata", "name": null }, { "creator_type": "author", "first_name": "Keiji", "last_name": "Shinozuka", "name": null }, { "creator_type": "author", "first_name": "Hidekazu", "last_name": "Nishikii", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Koganemaru", "name": null }, { "creator_type": "author", "first_name": "Shigeru", "last_name": "Chiba", "name": null }, { "creator_type": "author", "first_name": "Hiroki", "last_name": "Bukawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.joms.2011.08.015" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "22079069" } }, "mesh": [ { "descriptor": "Antibiotics, Antineoplastic", "descriptor_ui": "D000903", "major_topic": false }, { "descriptor": "Antineoplastic Agents, Alkylating", "descriptor_ui": "D018906", "major_topic": false }, { "descriptor": "Antineoplastic Agents, Hormonal", "descriptor_ui": "D018931", "major_topic": false }, { "descriptor": "Antineoplastic Agents, Phytogenic", "descriptor_ui": "D000972", "major_topic": false }, { "descriptor": "Antineoplastic Combined Chemotherapy Protocols", "descriptor_ui": "D000971", "major_topic": false }, { "descriptor": "Antiretroviral Therapy, Highly Active", "descriptor_ui": "D023241", "major_topic": false }, { "descriptor": "Burkitt Lymphoma", "descriptor_ui": "D002051", "major_topic": false }, { "descriptor": "Cyclophosphamide", "descriptor_ui": "D003520", "major_topic": false }, { "descriptor": "Doxorubicin", "descriptor_ui": "D004317", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Follow-Up Studies", "descriptor_ui": "D005500", "major_topic": false }, { "descriptor": "Gingival Neoplasms", "descriptor_ui": "D005887", "major_topic": false }, { "descriptor": "HIV Infections", "descriptor_ui": "D015658", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Lymphoma, AIDS-Related", "descriptor_ui": "D016483", "major_topic": false }, { "descriptor": "Mandibular Neoplasms", "descriptor_ui": "D008339", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Prednisone", "descriptor_ui": "D011241", "major_topic": false }, { "descriptor": "Radiotherapy, Adjuvant", "descriptor_ui": "D018714", "major_topic": false }, { "descriptor": "Vincristine", "descriptor_ui": "D014750", "major_topic": false } ], "publication": { "conference_name": null, "date": "2012 Aug", "date_precision": "unknown", "issue": "8", "normalized_date": null, "pages": "1885-1890", "proceedings_title": null, "publisher": "", "title": "Journal of oral and maxillofacial surgery : official journal of the American Association of Oral and Maxillofacial Surgeons", "volume": "70", "year": 2012 }, "ssbd": { "database": [], "repository": [] }, "title": "Human immunodeficiency virus-associated Burkitt's lymphoma in oral cavity of Japanese patient.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Single-nucleotide polymorphism genotyping microarray (SNP array) analysis provides detailed information on chromosomal copy number aberrations. To obtain detailed information on genomic abnormalities related to pathogenesis or prognosis of multiple myeloma (MM), we performed 250K SNP array analysis in 39 MM patients and 11 cell lines. We identified an accumulation of deletions and uniparental disomies at 22q12.1. Among the hyperdiploid MM cases, chromosomal imbalance at this locus was associated with poor prognosis. On sequencing, we also found a mutation in the seizure-related 6 homolog (mouse)-like (SEZ6L) gene located at ch.22q12.1 in an MM cell line, NOP1. We further found isolated deletions in 17 genes, five of which are known tumor suppressor genes. Of these, deletion of protein tyrosine phosphatase, receptor type D (PTPRD) was found in three samples, including two patients. Consistent with previous reports, non-hyperdiploid MM, deletion of 13q (del13q) and gain of 1q in non-hyperdiploid MMs were predictive of poor prognosis (p = 0.039, p = 0.049, and p = 0.013, respectively). However, our analysis revealed that unless accompanied by gain of 1q, the prognosis of non-hyperdiploid MM was as good as that of hyperdiploid MM. Thus, SNP array analysis provides significant information useful to understanding the pathogenesis and prognosis of MM.", "classifications": [ { "id": "Nishikii", "label": "Group Nishikii", "parent": "Shintaku", "type": "group" }, { "id": "Shintaku", "label": "Team Shintaku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yuhei", "last_name": "Kamada", "name": null }, { "creator_type": "author", "first_name": "Mamiko", "last_name": "Sakata-Yanagimoto", "name": null }, { "creator_type": "author", "first_name": "Masashi", "last_name": "Sanada", "name": null }, { "creator_type": "author", "first_name": "Aiko", "last_name": "Sato-Otsubo", "name": null }, { "creator_type": "author", "first_name": "Terukazu", "last_name": "Enami", "name": null }, { "creator_type": "author", "first_name": "Kazumi", "last_name": "Suzukawa", "name": null }, { "creator_type": "author", "first_name": "Naoki", "last_name": "Kurita", "name": null }, { "creator_type": "author", "first_name": "Hidekazu", "last_name": "Nishikii", "name": null }, { "creator_type": "author", "first_name": "Yasuhisa", "last_name": "Yokoyama", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Okoshi", "name": null }, { "creator_type": "author", "first_name": "Yuichi", "last_name": "Hasegawa", "name": null }, { "creator_type": "author", "first_name": "Seishi", "last_name": "Ogawa", "name": null }, { "creator_type": "author", "first_name": "Shigeru", "last_name": "Chiba", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/s12185-012-1171-1" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "22972171" } }, "mesh": [ { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Aged, 80 and over", "descriptor_ui": "D000369", "major_topic": false }, { "descriptor": "Chromosome Aberrations", "descriptor_ui": "D002869", "major_topic": false }, { "descriptor": "Chromosomes, Human, Pair 9", "descriptor_ui": "D002899", "major_topic": false }, { "descriptor": "DNA Copy Number Variations", "descriptor_ui": "D056915", "major_topic": true }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "In Situ Hybridization, Fluorescence", "descriptor_ui": "D017404", "major_topic": false }, { "descriptor": "Karyotyping", "descriptor_ui": "D007621", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Multiple Myeloma", "descriptor_ui": "D009101", "major_topic": false }, { "descriptor": "Polymorphism, Single Nucleotide", "descriptor_ui": "D020641", "major_topic": true }, { "descriptor": "Prognosis", "descriptor_ui": "D011379", "major_topic": false }, { "descriptor": "Receptor-Like Protein Tyrosine Phosphatases, Class 2", "descriptor_ui": "D054623", "major_topic": false } ], "publication": { "conference_name": null, "date": "2012 Oct", "date_precision": "unknown", "issue": "4", "normalized_date": null, "pages": "492-500", "proceedings_title": null, "publisher": "", "title": "International journal of hematology", "volume": "96", "year": 2012 }, "ssbd": { "database": [], "repository": [] }, "title": "Identification of unbalanced genome copy number abnormalities in patients with multiple myeloma by single-nucleotide polymorphism genotyping microarray analysis.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Retinoic acid related orphan receptor gamma-t (RORgammat) is known to be a master regulator of Th17-cell development. In this study, we generated RORgammat-overexpressing transgenic (RORgammat Tg) mice in which transgene expression was driven by the CD2 promoter, and found that these mice developed polyclonal plasmacytosis and autoantibody production. RORgammat Tg mice were generated on a C57BL/6 background, and also were intercrossed with BALB/c mice. BALB/c F1 (BALB/F1) RORgammat Tg mice developed massive polyclonal plasma-cytosis, and had shorter life spans. Splenomegaly and infiltration of plasma cells into the lung were observed. Hyperglobulinemia, anti-double-stranded DNA antibodies, anti-erythrocyte antibodies, and anti-platelet antibodies were detected in BALB/F1 RORgammat Tg mice. In the present study, polyclonal plasmacytosis in BALB/F1 RORgammat Tg mice appeared to be due to the induction of excessive IL-6 production by IL-17. We detected increased numbers of CD11b(+) cells that produced IL-6. We also generatedIL-6-deficient RORgammat Tg BALB/F1 background mice, which displayed high levels of serum IL-17, but did not develop severe hyperglobulinemia. Excessive IL-6 production by several cell types, including macrophages, in BALB/F1 RORgammat Tg mice, might effect the development of plasma-cytosis. These results suggest that RORgammat plays important roles in the development of plasmacytosis and autoantibody production.", "classifications": [ { "id": "Nishikii", "label": "Group Nishikii", "parent": "Shintaku", "type": "group" }, { "id": "Shintaku", "label": "Team Shintaku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Keigyou", "last_name": "Yoh", "name": null }, { "creator_type": "author", "first_name": "Naoki", "last_name": "Morito", "name": null }, { "creator_type": "author", "first_name": "Masami", "last_name": "Ojima", "name": null }, { "creator_type": "author", "first_name": "Kazuko", "last_name": "Shibuya", "name": null }, { "creator_type": "author", "first_name": "Yumi", "last_name": "Yamashita", "name": null }, { "creator_type": "author", "first_name": "Yuko", "last_name": "Morishima", "name": null }, { "creator_type": "author", "first_name": "Yukio", "last_name": "Ishii", "name": null }, { "creator_type": "author", "first_name": "Manabu", "last_name": "Kusakabe", "name": null }, { "creator_type": "author", "first_name": "Hidekazu", "last_name": "Nishikii", "name": null }, { "creator_type": "author", "first_name": "Akiko", "last_name": "Fujita", "name": null }, { "creator_type": "author", "first_name": "Emi", "last_name": "Matsunaga", "name": null }, { "creator_type": "author", "first_name": "Midori", "last_name": "Okamura", "name": null }, { "creator_type": "author", "first_name": "Michito", "last_name": "Hamada", "name": null }, { "creator_type": "author", "first_name": "Akira", "last_name": "Suto", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Nakajima", "name": null }, { "creator_type": "author", "first_name": "Akira", "last_name": "Shibuya", "name": null }, { "creator_type": "author", "first_name": "Kunihiro", "last_name": "Yamagata", "name": null }, { "creator_type": "author", "first_name": "Satoru", "last_name": "Takahashi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/eji.201142250" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "22623033" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Autoantibodies", "descriptor_ui": "D001323", "major_topic": false }, { "descriptor": "Blood Platelets", "descriptor_ui": "D001792", "major_topic": false }, { "descriptor": "CD11b Antigen", "descriptor_ui": "D039481", "major_topic": false }, { "descriptor": "CD2 Antigens", "descriptor_ui": "D018801", "major_topic": false }, { "descriptor": "DNA", "descriptor_ui": "D004247", "major_topic": false }, { "descriptor": "Erythrocytes", "descriptor_ui": "D004912", "major_topic": false }, { "descriptor": "Interleukin-17", "descriptor_ui": "D020381", "major_topic": false }, { "descriptor": "Interleukin-6", "descriptor_ui": "D015850", "major_topic": false }, { "descriptor": "Lung", "descriptor_ui": "D008168", "major_topic": false }, { "descriptor": "Macrophages", "descriptor_ui": "D008264", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred BALB C", "descriptor_ui": "D008807", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Transgenic", "descriptor_ui": "D008822", "major_topic": false }, { "descriptor": "Nuclear Receptor Subfamily 1, Group F, Member 3", "descriptor_ui": "D057132", "major_topic": false }, { "descriptor": "Plasma Cells", "descriptor_ui": "D010950", "major_topic": false }, { "descriptor": "Promoter Regions, Genetic", "descriptor_ui": "D011401", "major_topic": true }, { "descriptor": "Purpura, Hyperglobulinemic", "descriptor_ui": "D011694", "major_topic": false }, { "descriptor": "Splenomegaly", "descriptor_ui": "D013163", "major_topic": false } ], "publication": { "conference_name": null, "date": "2012 Aug", "date_precision": "unknown", "issue": "8", "normalized_date": null, "pages": "1999-2009", "proceedings_title": null, "publisher": "", "title": "European journal of immunology", "volume": "42", "year": 2012 }, "ssbd": { "database": [], "repository": [] }, "title": "Overexpression of RORgammat under control of the CD2 promoter induces polyclonal plasmacytosis and autoantibody production in transgenic mice.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "", "classifications": [ { "id": "Takekawa", "label": "Group Takekawa", "parent": "Takekawa", "type": "group" }, { "id": "Takekawa", "label": "Team Takekawa", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Takanori", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Mutsuhiro", "last_name": "Takekawa", "name": null } ], "identifiers": { "doi": { "normalized": null }, "pmcid": { "normalized": null }, "pmid": { "normalized": "23513840" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Arthritis, Rheumatoid", "descriptor_ui": "D001172", "major_topic": false }, { "descriptor": "Cerebral Infarction", "descriptor_ui": "D002544", "major_topic": false }, { "descriptor": "Diabetes Mellitus, Type 2", "descriptor_ui": "D003924", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "MAP Kinase Signaling System", "descriptor_ui": "D020935", "major_topic": false }, { "descriptor": "Molecular Targeted Therapy", "descriptor_ui": "D058990", "major_topic": false }, { "descriptor": "Multiple Myeloma", "descriptor_ui": "D009101", "major_topic": false }, { "descriptor": "p38 Mitogen-Activated Protein Kinases", "descriptor_ui": "D048051", "major_topic": false }, { "descriptor": "Parkinsonian Disorders", "descriptor_ui": "D020734", "major_topic": false }, { "descriptor": "Pulmonary Disease, Chronic Obstructive", "descriptor_ui": "D029424", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": true } ], "publication": { "conference_name": null, "date": "2012 Nov", "date_precision": "unknown", "issue": "", "normalized_date": null, "pages": "218-224", "proceedings_title": null, "publisher": "", "title": "Nihon rinsho. Japanese journal of clinical medicine", "volume": "70 Suppl 8", "year": 2012 }, "ssbd": { "database": [], "repository": [] }, "title": "[Targeting the stress-responsive JNK/p38-AP1 pathway for therapeutic intervention].", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Notch signaling regulates intestinal development, homeostasis and tumorigenesis, but its precise downstream mechanism remains largely unknown. Here we found that inactivation of the Notch effectors Hes1, Hes3 and Hes5, but not Hes1 alone, led to reduced cell proliferation, increased secretory cell formation and altered intestinal structures in adult mice. However, in Apc mutation-induced intestinal tumors, inactivation of Hes1 alone was sufficient for reducing tumor cell proliferation and inducing differentiation of tumor cells into all types of intestinal epithelial cells, but without affecting the homeostasis of normal crypts owing to genetic redundancy. These results indicated that Hes genes cooperatively regulate intestinal development and homeostasis and raised the possibility that Hes1 is a promising target to induce the differentiation of tumor cells.", "classifications": [ { "id": "Imayoshi", "label": "Group Imayoshi", "parent": "Imayoshi", "type": "group" }, { "id": "Imayoshi", "label": "Team Imayoshi", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Taro", "last_name": "Ueo", "name": null }, { "creator_type": "author", "first_name": "Itaru", "last_name": "Imayoshi", "name": null }, { "creator_type": "author", "first_name": "Taeko", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Toshiyuki", "last_name": "Ohtsuka", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Seno", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Nakase", "name": null }, { "creator_type": "author", "first_name": "Tsutomu", "last_name": "Chiba", "name": null }, { "creator_type": "author", "first_name": "Ryoichiro", "last_name": "Kageyama", "name": null } ], "identifiers": { "doi": { "normalized": "10.1242/dev.069070" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "22318232" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Basic Helix-Loop-Helix Proteins", "descriptor_ui": "D051792", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Cell Movement", "descriptor_ui": "D002465", "major_topic": false }, { "descriptor": "Cell Proliferation", "descriptor_ui": "D049109", "major_topic": false }, { "descriptor": "Cell Transformation, Neoplastic", "descriptor_ui": "D002471", "major_topic": false }, { "descriptor": "Epithelial Cells", "descriptor_ui": "D004847", "major_topic": false }, { "descriptor": "Genes, APC", "descriptor_ui": "D017491", "major_topic": false }, { "descriptor": "Homeodomain Proteins", "descriptor_ui": "D018398", "major_topic": false }, { "descriptor": "Intestinal Neoplasms", "descriptor_ui": "D007414", "major_topic": false }, { "descriptor": "Intestine, Large", "descriptor_ui": "D007420", "major_topic": false }, { "descriptor": "Intestine, Small", "descriptor_ui": "D007421", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Nerve Tissue Proteins", "descriptor_ui": "D009419", "major_topic": false }, { "descriptor": "Receptors, Notch", "descriptor_ui": "D051880", "major_topic": false }, { "descriptor": "Repressor Proteins", "descriptor_ui": "D012097", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Stem Cells", "descriptor_ui": "D013234", "major_topic": false }, { "descriptor": "Transcription Factor HES-1", "descriptor_ui": "D000072056", "major_topic": false } ], "publication": { "conference_name": null, "date": "2012 Mar", "date_precision": "unknown", "issue": "6", "normalized_date": null, "pages": "1071-1082", "proceedings_title": null, "publisher": "", "title": "Development (Cambridge, England)", "volume": "139", "year": 2012 }, "ssbd": { "database": [], "repository": [] }, "title": "The role of Hes genes in intestinal development, homeostasis and tumor formation.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "", "classifications": [ { "id": "Sawano", "label": "Group Sawano", "parent": "Shintaku", "type": "group" }, { "id": "Shintaku", "label": "Team Shintaku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Asako", "last_name": "Sakaue-Sawano", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Miyawaki", "name": null } ], "identifiers": { "doi": { "normalized": null }, "pmcid": { "normalized": null }, "pmid": { "normalized": "22416473" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Cycle", "descriptor_ui": "D002453", "major_topic": true }, { "descriptor": "Drug Design", "descriptor_ui": "D015195", "major_topic": false }, { "descriptor": "Drug Evaluation, Preclinical", "descriptor_ui": "D004353", "major_topic": false }, { "descriptor": "Fluorescent Dyes", "descriptor_ui": "D005456", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Lentivirus", "descriptor_ui": "D016086", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Transgenic", "descriptor_ui": "D008822", "major_topic": false }, { "descriptor": "Molecular Imaging", "descriptor_ui": "D057054", "major_topic": false }, { "descriptor": "Proteasome Endopeptidase Complex", "descriptor_ui": "D046988", "major_topic": false }, { "descriptor": "Ubiquitin", "descriptor_ui": "D025801", "major_topic": false }, { "descriptor": "Ubiquitin-Protein Ligases", "descriptor_ui": "D044767", "major_topic": false } ], "publication": { "conference_name": null, "date": "2012 Jan", "date_precision": "unknown", "issue": "1", "normalized_date": null, "pages": "47-52", "proceedings_title": null, "publisher": "", "title": "Seikagaku. The Journal of Japanese Biochemical Society", "volume": "84", "year": 2012 }, "ssbd": { "database": [], "repository": [] }, "title": "[Visualizing spatiotemporal dynamics of multicellular cell-cycle progression].", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Genome engineering strategies employing site-specific recombinases (SSRs) such as Cre, Flp and PhiC31, have become powerful tools to analyze gene function and manipulate neural network in vertebrates. In the present study, we evaluated the ability of PhiC31 phage integrase to induce genomic recombination in transgenic mice. PhiC31 is the integrase encoded by the Streptomyces bacteriophage that promotes recombination between heterotypic attP and attB sites. We generated transgenic mice that express codon-optimized PhiC31 (PhiC31o) in neural stem/progenitor cells or tyrosine hydroxylase (TH) expressing catecholaminergic neurons. PhiC31 was functional in these cells and capable of excising a transcriptional stop cassette flanked by PhiC31-specific attP/B recognition sites. PhiC31-ER(T2), a fusion protein of PhiC31o (without the nuclear localization signal) and the mutated ligand-binding domain of the human estrogen receptor, was able to induce recombination in neural stem/progenitor cells in a tamoxifen-dependent manner, but the recombination rate was less efficient than for PhiC31. Thus, PhiC31 integrase is functional in transgenic mice and is suitable for mosaic recombination in restricted cell populations.", "classifications": [ { "id": "Imayoshi", "label": "Group Imayoshi", "parent": "Imayoshi", "type": "group" }, { "id": "Imayoshi", "label": "Team Imayoshi", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Itaru", "last_name": "Imayoshi", "name": null }, { "creator_type": "author", "first_name": "Kyoko", "last_name": "Hirano", "name": null }, { "creator_type": "author", "first_name": "Satsuki", "last_name": "Kitano", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Miyachi", "name": null }, { "creator_type": "author", "first_name": "Ryoichiro", "last_name": "Kageyama", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.neures.2012.02.008" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "22608021" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Bacteriophages", "descriptor_ui": "D001435", "major_topic": false }, { "descriptor": "Enzyme Activation", "descriptor_ui": "D004789", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Genetic Engineering", "descriptor_ui": "D005818", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Transgenic", "descriptor_ui": "D008822", "major_topic": false }, { "descriptor": "Neural Stem Cells", "descriptor_ui": "D058953", "major_topic": false }, { "descriptor": "Recombinases", "descriptor_ui": "D045522", "major_topic": false }, { "descriptor": "Recombination, Genetic", "descriptor_ui": "D011995", "major_topic": false } ], "publication": { "conference_name": null, "date": "2012 Jun", "date_precision": "unknown", "issue": "2", "normalized_date": null, "pages": "106-114", "proceedings_title": null, "publisher": "", "title": "Neuroscience research", "volume": "73", "year": 2012 }, "ssbd": { "database": [], "repository": [] }, "title": "In vivo evaluation of PhiC31 recombinase activity in transgenic mice.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Minute pulmonary meningothelial-like nodules (PMNs) are asymptomatic, small nodules that are occasionally detected in surgical or autopsy specimens. Recent improvements in tumor imaging and the increased use of computed tomography (CT) scans of the chest have led to the early detection of these pulmonary nodules in various clinical settings, often before surgery or health examinations. However, large PMNs have rarely been observed. In this study, we report a patient with a large PMN, which was almost identical to so-called 'primary pulmonary meningioma'. A CT scan of his chest revealed a small, well-circumscribed nodule. Immunohistochemical analysis of the tumor revealed that the tumor cells were positive for CD56, epithelial membrane antigen, and progesterone receptor. Given the similarity of these results to the staining pattern of minute PMNs in previous reports, we suggest that the primary pulmonary meningiomas reported to date are, in fact, a giant form of PMN.", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Katsuhiro", "last_name": "Masago", "name": null }, { "creator_type": "author", "first_name": "Waki", "last_name": "Hosada", "name": null }, { "creator_type": "author", "first_name": "Eiichi", "last_name": "Sasaki", "name": null }, { "creator_type": "author", "first_name": "Yoshiko", "last_name": "Murakami", "name": null }, { "creator_type": "author", "first_name": "Masato", "last_name": "Sugano", "name": null }, { "creator_type": "author", "first_name": "Toru", "last_name": "Nagasaka", "name": null }, { "creator_type": "author", "first_name": "Mai", "last_name": "Yamada", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null } ], "identifiers": { "doi": { "normalized": "10.1159/000342391" }, "pmcid": { "normalized": "PMC3457042" }, "pmid": { "normalized": "23109924" } }, "mesh": [], "publication": { "conference_name": null, "date": "2012 May", "date_precision": "unknown", "issue": "2", "normalized_date": null, "pages": "471-478", "proceedings_title": null, "publisher": "", "title": "Case reports in oncology", "volume": "5", "year": 2012 }, "ssbd": { "database": [], "repository": [] }, "title": "Is primary pulmonary meningioma a giant form of a meningothelial-like nodule? A case report and review of the literature.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "We present the case of a 78-year-old Japanese woman with adenoendocrine cell carcinoma of the gallbladder accompanied by a high serum alpha-fetoprotein level. The patient visited our hospital with a complaint of a large mass in the right hypochondrium. Ultrasonography and computed tomography revealed multiple large hepatic tumors, swelling of lymph nodes in the hepatic hilum and para-aortic regions, and a slightly irregular gallbladder wall. The serum alpha-fetoprotein level was 157,428 ng/mL. We initially suspected scirrhous hepatocellular carcinoma, sarcomatous hepatocellular carcinoma, biliary tract cancer, or pancreatic cancer. However, the hepatic tumor biopsy was histologically diagnosed as undifferentiated adenocarcinoma. Immunohistochemical analysis demonstrated that the tumor was positive for cytokeratin 19, focally positive for cytokeratin 7, but negative for hepatocyte paraffin 1 and cytokeratin 20, suggestive of biliary tract carcinoma. Although the patient received a course of hepatic arterial infusion chemotherapy with cisplatin, she died 2 months after admission. Histopathological examination at autopsy revealed that the hepatic tumor was adenoendocrine cell carcinoma of the gallbladder, which was positive for cytokeratin 19, focally positive for cytokeratin 7, chromogranin A, synaptophysin, and weakly positive for alpha-fetoprotein. Labeling index of Ki-67 was 28 %. Interestingly, this was the first case report of adenoendocrine cell carcinoma of the gallbladder that produced a high level of alpha-fetoprotein, which hampered correct diagnosis before autopsy.", "classifications": [ { "id": "Tanaka", "label": "Group Tanaka", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Hideki", "last_name": "Fujii", "name": null }, { "creator_type": "author", "first_name": "Kanji", "last_name": "Yamaguchi", "name": null }, { "creator_type": "author", "first_name": "Naoki", "last_name": "Ohnishi", "name": null }, { "creator_type": "author", "first_name": "Masafumi", "last_name": "Sakamoto", "name": null }, { "creator_type": "author", "first_name": "Tohru", "last_name": "Ohkawara", "name": null }, { "creator_type": "author", "first_name": "Yoshihiko", "last_name": "Sawa", "name": null }, { "creator_type": "author", "first_name": "Koichi", "last_name": "Nishida", "name": null }, { "creator_type": "author", "first_name": "Yasuo", "last_name": "Ohkawara", "name": null }, { "creator_type": "author", "first_name": "Yoshinori", "last_name": "Harada", "name": null }, { "creator_type": "author", "first_name": "Hideo", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Tetsuro", "last_name": "Takamatsu", "name": null }, { "creator_type": "author", "first_name": "Yoshito", "last_name": "Itoh", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/s12328-012-0311-8" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "26182391" } }, "mesh": [], "publication": { "conference_name": null, "date": "2012 Aug", "date_precision": "unknown", "issue": "4", "normalized_date": null, "pages": "261-267", "proceedings_title": null, "publisher": "", "title": "Clinical journal of gastroenterology", "volume": "5", "year": 2012 }, "ssbd": { "database": [], "repository": [] }, "title": "Adenoendocrine cell carcinoma of the gallbladder producing a high level of alpha-fetoprotein.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Entamoeba histolytica, a microaerophilic enteric protozoan parasite, causes amebic colitis and extra intestinal abscesses in millions of inhabitants of endemic areas. Trophozoites of E. histolytica are exposed to a variety of reactive oxygen and nitrogen species during infection. Since E. histolytica lacks key components of canonical eukaryotic anti-oxidative defense systems, such as catalase and glutathione system, alternative not-yet-identified anti-oxidative defense strategies have been postulated to be operating in E. histolytica. In the present study, we investigated global metabolic responses in E. histolytica in response to H2O2- and paraquat-mediated oxidative stress by measuring charged metabolites on capillary electrophoresis and time-of-flight mass spectrometry. We found that oxidative stress caused drastic modulation of metabolites involved in glycolysis, chitin biosynthesis, and nucleotide and amino acid metabolism. Oxidative stress resulted in the inhibition of glycolysis as a result of inactivation of several key enzymes, leading to the redirection of metabolic flux towards glycerol production, chitin biosynthesis, and the non-oxidative branch of the pentose phosphate pathway. As a result of the repression of glycolysis as evidenced by the accumulation of glycolytic intermediates upstream of pyruvate, and reduced ethanol production, the levels of nucleoside triphosphates were decreased. We also showed for the first time the presence of functional glycerol biosynthetic pathway in E. histolytica as demonstrated by the increased production of glycerol 3-phosphate and glycerol upon oxidative stress. We proposed the significance of the glycerol biosynthetic pathway as a metabolic anti-oxidative defense system in E. histolytica.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Afzal", "last_name": "Husain", "name": null }, { "creator_type": "author", "first_name": "Dan", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Ghulam", "last_name": "Jeelani", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Nozaki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1371/journal.pntd.0001831" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "23029590" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Electrophoresis, Capillary", "descriptor_ui": "D019075", "major_topic": false }, { "descriptor": "Entamoeba histolytica", "descriptor_ui": "D004748", "major_topic": false }, { "descriptor": "Glycerol", "descriptor_ui": "D005990", "major_topic": false }, { "descriptor": "Hydrogen Peroxide", "descriptor_ui": "D006861", "major_topic": false }, { "descriptor": "Metabolome", "descriptor_ui": "D055442", "major_topic": false }, { "descriptor": "Oxidative Stress", "descriptor_ui": "D018384", "major_topic": true }, { "descriptor": "Paraquat", "descriptor_ui": "D010269", "major_topic": false }, { "descriptor": "Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization", "descriptor_ui": "D019032", "major_topic": false }, { "descriptor": "Stress, Physiological", "descriptor_ui": "D013312", "major_topic": true } ], "publication": { "conference_name": null, "date": "2012 Sep", "date_precision": "unknown", "issue": "9", "normalized_date": null, "pages": "", "proceedings_title": null, "publisher": "", "title": "PLoS Neglected Tropical Diseases", "volume": "6", "year": 2012 }, "ssbd": { "database": [], "repository": [] }, "title": "Dramatic Increase in Glycerol Biosynthesis upon Oxidative Stress in the Anaerobic Protozoan Parasite Entamoeba histolytica.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The oral adsorbent AST-120 is composed of spherical carbon particles and has an adsorption ability for certain small-molecular-weight compounds that accumulate in patients with chronic kidney disease (CKD). So far, very few compounds are known to be adsorbed by AST-120 in vivo. To examine the effect of AST-120 in vivo, we comprehensively evaluated the plasma concentrations of 146 compounds (61 anions and 85 cations) in CKD model rats, with or without four weeks of treatment with AST-120. By capillary electrophoresis with mass spectrometry, we identified 6 anions and 17 cations that were significantly decreased by AST-120 treatment. In contrast, we also identified 2 cations that were significantly increased by AST-120. Among them, 4 anions, apart from indoxyl sulfate and hippurate, and 19 cations were newly identified in this study. The plasma levels of N-acetyl-neuraminate, 4-pyridoxate, 4-oxopentanoate, glycine, γ-guanidinobutyrate, N-γ-ethylglutamine, allantoin, cytosine, 5-methylcytosine and imidazole-4-acetate were significantly increased in the CKD model compared with the sham-operated group, and were significantly decreased by AST-120 treatment. Therefore, these 10 compounds could be added as uremic compounds that indicate the effect of AST-120 treatment. This study provides useful information not only for identifying the indicators of AST-120, but also for clarifying changes in the metabolic profile by AST-120 treatment in the clinical setting.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yasutoshi", "last_name": "Akiyama", "name": null }, { "creator_type": "author", "first_name": "Yoichi", "last_name": "Takeuchi", "name": null }, { "creator_type": "author", "first_name": "Koichi", "last_name": "Kikuchi", "name": null }, { "creator_type": "author", "first_name": "Eikan", "last_name": "Mishima", "name": null }, { "creator_type": "author", "first_name": "Yasuaki", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Chitose", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Takafumi", "last_name": "Toyohara", "name": null }, { "creator_type": "author", "first_name": "Takehiro", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Hozawa", "name": null }, { "creator_type": "author", "first_name": "Sadayoshi", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Takaaki", "last_name": "Abe", "name": null } ], "identifiers": { "doi": { "normalized": "10.3390/toxins4111309" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "23202318" } }, "mesh": [ { "descriptor": "Administration, Oral", "descriptor_ui": "D000284", "major_topic": false }, { "descriptor": "Adsorption", "descriptor_ui": "D000327", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Anions", "descriptor_ui": "D000838", "major_topic": false }, { "descriptor": "Carbon", "descriptor_ui": "D002244", "major_topic": false }, { "descriptor": "Cations", "descriptor_ui": "D002412", "major_topic": false }, { "descriptor": "Disease Models, Animal", "descriptor_ui": "D004195", "major_topic": false }, { "descriptor": "Electrophoresis, Capillary", "descriptor_ui": "D019075", "major_topic": false }, { "descriptor": "Kidney Function Tests", "descriptor_ui": "D007677", "major_topic": false }, { "descriptor": "Mass Spectrometry", "descriptor_ui": "D013058", "major_topic": false }, { "descriptor": "Metabolome", "descriptor_ui": "D055442", "major_topic": true }, { "descriptor": "Metabolomics", "descriptor_ui": "D055432", "major_topic": false }, { "descriptor": "Nephrectomy", "descriptor_ui": "D009392", "major_topic": false }, { "descriptor": "Oxides", "descriptor_ui": "D010087", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Rats, Wistar", "descriptor_ui": "D017208", "major_topic": false }, { "descriptor": "Renal Insufficiency, Chronic", "descriptor_ui": "D051436", "major_topic": false }, { "descriptor": "Toxins, Biological", "descriptor_ui": "D014118", "major_topic": false }, { "descriptor": "Uremia", "descriptor_ui": "D014511", "major_topic": false } ], "publication": { "conference_name": null, "date": "2012 Nov", "date_precision": "unknown", "issue": "11", "normalized_date": null, "pages": "1309-1322", "proceedings_title": null, "publisher": "", "title": "Toxins", "volume": "4", "year": 2012 }, "ssbd": { "database": [], "repository": [] }, "title": "A Metabolomic Approach to Clarifying the Effect of AST-120 on 5/6 Nephrectomized Rats by Capillary Electrophoresis with Mass Spectrometry (CE-MS).", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "MT1-MMP is a potent invasion-promoting membrane protease employed by aggressive cancer cells. MT1-MMP localizes preferentially at membrane protrusions called invadopodia where it plays a central role in degradation of the surrounding extracellular matrix (ECM). Previous reports suggested a role for a continuous supply of MT1-MMP in ECM degradation. However, the turnover rate of MT1-MMP and the extent to which the turnover contributes to the ECM degradation at invadopodia have not been clarified. To approach this problem, we first performed FRAP (Fluorescence Recovery after Photobleaching) experiments with fluorescence-tagged MT1-MMP focusing on a single invadopodium and found very rapid recovery in FRAP signals, approximated by double-exponential plots with time constants of 26 s and 259 s. The recovery depended primarily on vesicle transport, but negligibly on lateral diffusion. Next we constructed a computational model employing the observed kinetics of the FRAP experiments. The simulations successfully reproduced our FRAP experiments. Next we inhibited the vesicle transport both experimentally, and in simulation. Addition of drugs inhibiting vesicle transport blocked ECM degradation experimentally, and the simulation showed no appreciable ECM degradation under conditions inhibiting vesicle transport. In addition, the degree of the reduction in ECM degradation depended on the degree of the reduction in the MT1-MMP turnover. Thus, our experiments and simulations have established the role of the rapid turnover of MT1-MMP in ECM degradation at invadopodia. Furthermore, our simulations suggested synergetic contributions of proteolytic activity and the MT1-MMP turnover to ECM degradation because there was a nonlinear and marked reduction in ECM degradation if both factors were reduced simultaneously. Thus our computational model provides a new in silico tool to design and evaluate intervention strategies in cancer cell invasion.", "classifications": [ { "id": "Suzuki", "label": "Group Suzuki", "parent": "Takekawa", "type": "group" }, { "id": "Takekawa", "label": "Team Takekawa", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Daisuke", "last_name": "Hoshino", "name": null }, { "creator_type": "author", "first_name": "Naohiko", "last_name": "Koshikawa", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Vito", "last_name": "Quaranta", "name": null }, { "creator_type": "author", "first_name": "Alissa M.", "last_name": "Weaver", "name": null }, { "creator_type": "author", "first_name": "Motoharu", "last_name": "Seiki", "name": null }, { "creator_type": "author", "first_name": "Kazuhisa", "last_name": "Ichikawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1371/journal.pcbi.1002479" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "22511862" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Carcinoma, Squamous Cell", "descriptor_ui": "D002294", "major_topic": false }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Cell Membrane", "descriptor_ui": "D002462", "major_topic": false }, { "descriptor": "Computer Simulation", "descriptor_ui": "D003198", "major_topic": false }, { "descriptor": "Extracellular Matrix", "descriptor_ui": "D005109", "major_topic": false }, { "descriptor": "Matrix Metalloproteinase 14", "descriptor_ui": "D053511", "major_topic": false }, { "descriptor": "Models, Biological", "descriptor_ui": "D008954", "major_topic": true }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": true } ], "publication": { "conference_name": null, "date": "2012 Apr", "date_precision": "unknown", "issue": "4", "normalized_date": null, "pages": "", "proceedings_title": null, "publisher": "", "title": "PLoS Computational Biology", "volume": "8", "year": 2012 }, "ssbd": { "database": [], "repository": [] }, "title": "Establishment and Validation of Computational Model for MT1-MMP Dependent ECM Degradation and Intervention Strategies.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Quail are thought to serve as intermediate hosts of influenza A viruses between aquatic birds and terrestrial birds, such as chickens, due to their high susceptibility to aquatic-bird viruses, which then adapt to replicate efficiently in their new hosts. However, does replication of aquatic-bird influenza viruses in quail similarly result in their efficient replication in humans? Using sialic acid-galactose linkage-specific lectins, we found both avian (sialic acid-α2-3-galactose [Siaα2-3Gal] linkages on sialyloligosaccharides)--and human (Siaα2-6Gal)-type receptors on the tracheal cells of quail, consistent with previous reports. We also passaged a duck H3N2 virus in quail 19 times. Sequence analysis revealed that eight mutations accumulated in hemagglutinin (HA) during these passages. Interestingly, many of the altered HA amino acids found in the adapted virus are present in human seasonal viruses, but not in duck viruses. We also found that stepwise stalk deletion of neuraminidase occurred during passages, resulting in reduced neuraminidase function. Despite some hemagglutinin mutations near the receptor binding pocket, appreciable changes in receptor specificity were not detected. However, reverse-genetics-generated viruses that possessed the hemagglutinin and neuraminidase of the quail-passaged virus replicated significantly better than the virus possessing the parent HA and neuraminidase in normal human bronchial epithelial cells, whereas no significant difference in replication between the two viruses was observed in duck cells. Further, the quail-passaged but not the original duck virus replicated in human bronchial epithelial cells. These data indicate that quail can serve as intermediate hosts for aquatic-bird influenza viruses to be transmitted to humans.", "classifications": [ { "id": "Suzuki", "label": "Group Suzuki", "parent": "Takekawa", "type": "group" }, { "id": "Takekawa", "label": "Team Takekawa", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Shinya", "last_name": "Yamada", "name": null }, { "creator_type": "author", "first_name": "Kyoko", "last_name": "Shinya", "name": null }, { "creator_type": "author", "first_name": "Ayato", "last_name": "Takada", "name": null }, { "creator_type": "author", "first_name": "Toshihiro", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Yasuo", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Quynh Mai", "last_name": "Le", "name": null }, { "creator_type": "author", "first_name": "Masahito", "last_name": "Ebina", "name": null }, { "creator_type": "author", "first_name": "Noriyuki", "last_name": "Kasai", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Kida", "name": null }, { "creator_type": "author", "first_name": "Taisuke", "last_name": "Horimoto", "name": null }, { "creator_type": "author", "first_name": "Pierre", "last_name": "Rivailler", "name": null }, { "creator_type": "author", "first_name": "Li Mei", "last_name": "Chen", "name": null }, { "creator_type": "author", "first_name": "Ruben O.", "last_name": "Donis", "name": null }, { "creator_type": "author", "first_name": "Yoshihiro", "last_name": "Kawaoka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1128/jvi.06100-11" }, "pmcid": { "normalized": "PMC3264366" }, "pmid": { "normalized": "22090115" } }, "mesh": [ { "descriptor": "Adaptation, Physiological", "descriptor_ui": "D000222", "major_topic": true }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "Dogs", "descriptor_ui": "D004285", "major_topic": false }, { "descriptor": "Ducks", "descriptor_ui": "D004372", "major_topic": false }, { "descriptor": "Hemagglutinin Glycoproteins, Influenza Virus", "descriptor_ui": "D019267", "major_topic": false }, { "descriptor": "Influenza A Virus, H3N2 Subtype", "descriptor_ui": "D053122", "major_topic": false }, { "descriptor": "Influenza in Birds", "descriptor_ui": "D005585", "major_topic": false }, { "descriptor": "Intestinal Mucosa", "descriptor_ui": "D007413", "major_topic": false }, { "descriptor": "Models, Molecular", "descriptor_ui": "D008958", "major_topic": false }, { "descriptor": "Quail", "descriptor_ui": "D011784", "major_topic": false }, { "descriptor": "Reverse Transcriptase Polymerase Chain Reaction", "descriptor_ui": "D020133", "major_topic": false }, { "descriptor": "Sialic Acids", "descriptor_ui": "D012794", "major_topic": false } ], "publication": { "conference_name": null, "date": "2012 Feb", "date_precision": "unknown", "issue": "3", "normalized_date": null, "pages": "1411-1420", "proceedings_title": null, "publisher": "", "title": "Journal of virology", "volume": "86", "year": 2012 }, "ssbd": { "database": [], "repository": [] }, "title": "Adaptation of a duck influenza A virus in quail.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "", "classifications": [ { "id": "Sodeoka", "label": "Group Sodeoka", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Mikiko", "last_name": "Sodeoka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1126/science.1215220" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "22194563" } }, "mesh": [], "publication": { "conference_name": null, "date": "2011 Dec 23", "date_precision": "day", "issue": "6063", "normalized_date": "2011-12-23", "pages": "1651-1652", "proceedings_title": null, "publisher": "", "title": "Science (New York, N.Y.)", "volume": "334", "year": 2011 }, "ssbd": { "database": [], "repository": [] }, "title": "Chemistry. Efficient fluorination of organic molecules with chiral anions.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Dynamic SERS imaging inside a living cell is demonstrated with the use of a gold nanoparticle, which travels through the intracellular space to probe local molecular information over time. Simultaneous tracking of particle motion and SERS spectroscopy allows us to detect intracellular molecules at 65 nm spatial resolution and 50 ms temporal resolution, providing molecular maps of organelle transport and lisosomal accumulation. Multiplex spectral and trajectory imaging will enable imaging of specific dynamic biological functions such as membrane protein diffusion, nuclear entry, and rearrangement of cellular cytoskeleton.", "classifications": [ { "id": "Fujita", "label": "Group Fujita", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Jun", "last_name": "Ando", "name": null }, { "creator_type": "author", "first_name": "Katsumasa", "last_name": "Fujita", "name": null }, { "creator_type": "author", "first_name": "Nicholas I.", "last_name": "Smith", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Kawata", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/nl202877r" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "22059676" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Biological Transport", "descriptor_ui": "D001692", "major_topic": false }, { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "Endocytosis", "descriptor_ui": "D004705", "major_topic": true }, { "descriptor": "Gold", "descriptor_ui": "D006046", "major_topic": false }, { "descriptor": "Macrophages", "descriptor_ui": "D008264", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Nanoparticles", "descriptor_ui": "D053758", "major_topic": false }, { "descriptor": "Spectrum Analysis, Raman", "descriptor_ui": "D013059", "major_topic": false } ], "publication": { "conference_name": null, "date": "2011 Dec 14", "date_precision": "day", "issue": "12", "normalized_date": "2011-12-14", "pages": "5344-5348", "proceedings_title": null, "publisher": "", "title": "Nano letters", "volume": "11", "year": 2011 }, "ssbd": { "database": [], "repository": [] }, "title": "Dynamic SERS imaging of cellular transport pathways with endocytosed gold nanoparticles.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Neurons of the ventrolateral preoptic nucleus (VLPO) promote sleep and VLPO loss produces insomnia. Previous studies show that general anesthetics including isoflurane activate VLPO neurons, and may contribute to their sedative effects. However, it is not clear to what extent the activation of VLPO neurons contributes to general anesthesia. We tested whether destruction of the VLPO neurons would affect the onset, depth, or recovery from isoflurane's general anesthetic effects. The VLPO was ablated in 25 rats by bilateral local injection of orexin-saporin, and polysomnography was performed to measure baseline sleep loss and responses to isoflurane anesthesia at 1% and 2%. Eight rats received sham (saline) injections. We measured isoflurane effects on time to loss of righting reflex, onset of continuous slow wave activity, and burst suppression; burst-suppression ratio; and time to recovery of righting reflex and desynchronized EEG. VLPO neuron cell loss was quantified by post hoc histology. Loss of VLPO neurons as well as lesion size were associated with cumulative sleep loss (r=0.77 and r=0.62, respectively), and cumulative sleep loss was the strongest predictor of high sensitivity to anesthesia, expressed as decreased time to loss of righting reflex (−0.59), increased burst-suppression ratio (r=0.52), and increased emergence time (r=0.54); an interaction-effect of isoflurane dose was observed (burst-suppression ratio: p<0.001). We conclude that the sleep loss caused by ablation of VLPO neurons sensitizes animals to the general anesthetic effects of isoflurane, but that the sedation produced by VLPO neurons themselves is not required for deep isoflurane anesthesia.", "classifications": [ { "id": "Yokota", "label": "Group Yokota", "parent": "Enomoto", "type": "group" }, { "id": "Enomoto", "label": "Team Enomoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Matthias", "last_name": "Eikermann", "name": null }, { "creator_type": "author", "first_name": "Ramalingam", "last_name": "Vetrivelan", "name": null }, { "creator_type": "author", "first_name": "Martina", "last_name": "Grosse-Sundrup", "name": null }, { "creator_type": "author", "first_name": "Mark E.", "last_name": "Henry", "name": null }, { "creator_type": "author", "first_name": "Ulrike", "last_name": "Hoffmann", "name": null }, { "creator_type": "author", "first_name": "Shigefumi", "last_name": "Yokota", "name": null }, { "creator_type": "author", "first_name": "Clifford B.", "last_name": "Saper", "name": null }, { "creator_type": "author", "first_name": "Nancy L.", "last_name": "Chamberlin", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.brainres.2011.10.018" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "22041226" } }, "mesh": [ { "descriptor": "Anesthesia, General", "descriptor_ui": "D000768", "major_topic": false }, { "descriptor": "Anesthetics, General", "descriptor_ui": "D018681", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Isoflurane", "descriptor_ui": "D007530", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Preoptic Area", "descriptor_ui": "D011301", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Rats, Sprague-Dawley", "descriptor_ui": "D017207", "major_topic": false }, { "descriptor": "Sleep", "descriptor_ui": "D012890", "major_topic": false } ], "publication": { "conference_name": null, "date": "2011 Dec 2", "date_precision": "day", "issue": "", "normalized_date": "2011-12-02", "pages": "30-37", "proceedings_title": null, "publisher": "", "title": "Brain research", "volume": "1426", "year": 2011 }, "ssbd": { "database": [], "repository": [] }, "title": "The Ventrolateral Preoptic Nucleus Is Not Required for Deep Isoflurane General Anesthesia.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The liver plays a central role in glucose homeostasis in the whole-body by responding to environmental factors including nutrients, hormones, and oxygen. In conditions of metabolic overload such as diabetes mellitus and obesity, coordinated regulation between oxygen supply and consumption has been reported to be disrupted and subsequently cause tissue hypoxia, although pathological significance of the disease-related hypoxia remains elusive. To investigate the role of tissue hypoxia in the liver on systemic glucose homeostasis, mice lacking HIF-1alpha gene, a critical component of a master regulator of hypoxic response, in hepatocytes were exposed to high fat/sucrose diet (HFSD). Exposure to HFSD for 5 weeks elicited liver hypoxia with a transient increase in HIF-1alpha protein expression in the liver of control mice. Glucose disposal was marginally impaired in control mice when challenged oral glucose tolerance test, but such impairment was enhanced in the mutant mice. This alteration was accompanied by a complete inhibition of glucokinase induction with a significant reduction of hepatic glucose uptake. Mice fed HFSD for 20 weeks exhibited fasting hyperglycemia and glucose intolerance, whereas these metabolic phenotypes deteriorated considerably with severe insulin resistance in skeletal muscles and adipose tissues in the mutant mice. These findings suggest that HIF-1 in hepatocytes plays protective roles against the progression of diabetes mellitus.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Daigo", "last_name": "Ochiai", "name": null }, { "creator_type": "author", "first_name": "Nobuhito", "last_name": "Goda", "name": null }, { "creator_type": "author", "first_name": "Takako", "last_name": "Hishiki", "name": null }, { "creator_type": "author", "first_name": "Mai", "last_name": "Kanai", "name": null }, { "creator_type": "author", "first_name": "Nanami", "last_name": "Senoo-Matsuda", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Randall S.", "last_name": "Johnson", "name": null }, { "creator_type": "author", "first_name": "Yasunori", "last_name": "Yoshimura", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Suematsu", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.bbrc.2011.10.089" }, "pmcid": { "normalized": "PMC6592821" }, "pmid": { "normalized": "22051049" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Diabetes Mellitus", "descriptor_ui": "D003920", "major_topic": false }, { "descriptor": "Diet, High-Fat", "descriptor_ui": "D059305", "major_topic": false }, { "descriptor": "Glucose", "descriptor_ui": "D005947", "major_topic": false }, { "descriptor": "Glucose Tolerance Test", "descriptor_ui": "D005951", "major_topic": false }, { "descriptor": "Hepatocytes", "descriptor_ui": "D022781", "major_topic": false }, { "descriptor": "Hypoxia-Inducible Factor 1, alpha Subunit", "descriptor_ui": "D051795", "major_topic": false }, { "descriptor": "Insulin Resistance", "descriptor_ui": "D007333", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Obese", "descriptor_ui": "D008820", "major_topic": false }, { "descriptor": "Obesity", "descriptor_ui": "D009765", "major_topic": false }, { "descriptor": "Sucrose", "descriptor_ui": "D013395", "major_topic": false } ], "publication": { "conference_name": null, "date": "2011 Nov 25", "date_precision": "day", "issue": "3", "normalized_date": "2011-11-25", "pages": "445-449", "proceedings_title": null, "publisher": "", "title": "Biochemical and biophysical research communications", "volume": "415", "year": 2011 }, "ssbd": { "database": [], "repository": [] }, "title": "Disruption of HIF-1alpha in hepatocytes impairs glucose metabolism in diet-induced obesity mice.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The Krebs cycle enzyme fumarate hydratase (FH) is a human tumor suppressor whose inactivation is associated with the development of leiomyomata, renal cysts, and tumors. It has been proposed that activation of hypoxia inducible factor (HIF) by fumarate-mediated inhibition of HIF prolyl hydroxylases drives oncogenesis. Using a mouse model, we provide genetic evidence that Fh1-associated cyst formation is Hif independent, as is striking upregulation of antioxidant signaling pathways revealed by gene expression profiling. Mechanistic analysis revealed that fumarate modifies cysteine residues within the Kelch-like ECH-associated protein 1 (KEAP1), abrogating its ability to repress the Nuclear factor (erythroid-derived 2)-like 2 (Nrf2)-mediated antioxidant response pathway, suggesting a role for Nrf2 dysregulation in FH-associated cysts and tumors.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Julie", "last_name": "Adam", "name": null }, { "creator_type": "author", "first_name": "Emine", "last_name": "Hatipoglu", "name": null }, { "creator_type": "author", "first_name": "Linda", "last_name": "O'Flaherty", "name": null }, { "creator_type": "author", "first_name": "Nicola", "last_name": "Ternette", "name": null }, { "creator_type": "author", "first_name": "Natasha", "last_name": "Sahgal", "name": null }, { "creator_type": "author", "first_name": "Helen", "last_name": "Lockstone", "name": null }, { "creator_type": "author", "first_name": "Dilair", "last_name": "Baban", "name": null }, { "creator_type": "author", "first_name": "Emma", "last_name": "Nye", "name": null }, { "creator_type": "author", "first_name": "Gordon W.", "last_name": "Stamp", "name": null }, { "creator_type": "author", "first_name": "Kathryn", "last_name": "Wolhuter", "name": null }, { "creator_type": "author", "first_name": "Marcus", "last_name": "Stevens", "name": null }, { "creator_type": "author", "first_name": "Roman", "last_name": "Fischer", "name": null }, { "creator_type": "author", "first_name": "Peter", "last_name": "Carmeliet", "name": null }, { "creator_type": "author", "first_name": "Patrick H.", "last_name": "Maxwell", "name": null }, { "creator_type": "author", "first_name": "Chris W.", "last_name": "Pugh", "name": null }, { "creator_type": "author", "first_name": "Norma", "last_name": "Frizzell", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Benedikt M.", "last_name": "Kessler", "name": null }, { "creator_type": "author", "first_name": "Mona", "last_name": "El-Bahrawy", "name": null }, { "creator_type": "author", "first_name": "Peter J.", "last_name": "Ratcliffe", "name": null }, { "creator_type": "author", "first_name": "Patrick J.", "last_name": "Pollard", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.ccr.2011.09.006" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "22014577" } }, "mesh": [ { "descriptor": "Adaptor Proteins, Signal Transducing", "descriptor_ui": "D048868", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Antioxidants", "descriptor_ui": "D000975", "major_topic": false }, { "descriptor": "Cell Hypoxia", "descriptor_ui": "D015687", "major_topic": false }, { "descriptor": "Cytoskeletal Proteins", "descriptor_ui": "D003598", "major_topic": false }, { "descriptor": "Fumarate Hydratase", "descriptor_ui": "D005649", "major_topic": false }, { "descriptor": "Fumarates", "descriptor_ui": "D005650", "major_topic": false }, { "descriptor": "Gene Expression Regulation, Neoplastic", "descriptor_ui": "D015972", "major_topic": false }, { "descriptor": "Hypoxia-Inducible Factor 1", "descriptor_ui": "D051793", "major_topic": false }, { "descriptor": "Kelch-Like ECH-Associated Protein 1", "descriptor_ui": "D000072019", "major_topic": false }, { "descriptor": "Kidney Diseases, Cystic", "descriptor_ui": "D052177", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "NF-E2-Related Factor 2", "descriptor_ui": "D051267", "major_topic": false }, { "descriptor": "Procollagen-Proline Dioxygenase", "descriptor_ui": "D011393", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Succinates", "descriptor_ui": "D013386", "major_topic": false } ], "publication": { "conference_name": null, "date": "2011 Oct 18", "date_precision": "day", "issue": "4", "normalized_date": "2011-10-18", "pages": "524-537", "proceedings_title": null, "publisher": "", "title": "Cancer Cell", "volume": "20", "year": 2011 }, "ssbd": { "database": [], "repository": [] }, "title": "Renal Cyst Formation in Fh1-Deficient Mice Is Independent of the Hif/Phd Pathway: Roles for Fumarate in KEAP1 Succination and Nrf2 Signaling.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Human induced pluripotent stem cells (iPSCs) represent a unique opportunity for regenerative medicine because they offer the prospect of generating unlimited quantities of cells for autologous transplantation, with potential application in treatments for a broad range of disorders. However, the use of human iPSCs in the context of genetically inherited human disease will require the correction of disease-causing mutations in a manner that is fully compatible with clinical applications. The methods currently available, such as homologous recombination, lack the necessary efficiency and also leave residual sequences in the targeted genome. Therefore, the development of new approaches to edit the mammalian genome is a prerequisite to delivering the clinical promise of human iPSCs. Here we show that a combination of zinc finger nucleases (ZFNs) and piggyBac technology in human iPSCs can achieve biallelic correction of a point mutation (Glu342Lys) in the alpha(1)-antitrypsin (A1AT, also known as SERPINA1) gene that is responsible for alpha(1)-antitrypsin deficiency. Genetic correction of human iPSCs restored the structure and function of A1AT in subsequently derived liver cells in vitro and in vivo. This approach is significantly more efficient than any other gene-targeting technology that is currently available and crucially prevents contamination of the host genome with residual non-human sequences. Our results provide the first proof of principle, to our knowledge, for the potential of combining human iPSCs with genetic correction to generate clinically relevant cells for autologous cell-based therapies.", "classifications": [ { "id": "Yusa", "label": "Group Yusa", "parent": "Eiraku", "type": "group" }, { "id": "Eiraku", "label": "Team Eiraku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Kosuke", "last_name": "Yusa", "name": null }, { "creator_type": "author", "first_name": "S. Tamir", "last_name": "Rashid", "name": null }, { "creator_type": "author", "first_name": "Helene", "last_name": "Strick-Marchand", "name": null }, { "creator_type": "author", "first_name": "Ignacio", "last_name": "Varela", "name": null }, { "creator_type": "author", "first_name": "Pei-Qi", "last_name": "Liu", "name": null }, { "creator_type": "author", "first_name": "David E.", "last_name": "Paschon", "name": null }, { "creator_type": "author", "first_name": "Elena", "last_name": "Miranda", "name": null }, { "creator_type": "author", "first_name": "Adriana", "last_name": "Ordonez", "name": null }, { "creator_type": "author", "first_name": "Nicholas R. F.", "last_name": "Hannan", "name": null }, { "creator_type": "author", "first_name": "Foad J.", "last_name": "Rouhani", "name": null }, { "creator_type": "author", "first_name": "Sylvie", "last_name": "Darche", "name": null }, { "creator_type": "author", "first_name": "Graeme", "last_name": "Alexander", "name": null }, { "creator_type": "author", "first_name": "Stefan J.", "last_name": "Marciniak", "name": null }, { "creator_type": "author", "first_name": "Noemi", "last_name": "Fusaki", "name": null }, { "creator_type": "author", "first_name": "Mamoru", "last_name": "Hasegawa", "name": null }, { "creator_type": "author", "first_name": "Michael C.", "last_name": "Holmes", "name": null }, { "creator_type": "author", "first_name": "James P.", "last_name": "Di Santo", "name": null }, { "creator_type": "author", "first_name": "David A.", "last_name": "Lomas", "name": null }, { "creator_type": "author", "first_name": "Allan", "last_name": "Bradley", "name": null }, { "creator_type": "author", "first_name": "Ludovic", "last_name": "Vallier", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/nature10424" }, "pmcid": { "normalized": "PMC3198846" }, "pmid": { "normalized": "21993621" } }, "mesh": [ { "descriptor": "alpha 1-Antitrypsin", "descriptor_ui": "D000515", "major_topic": false }, { "descriptor": "alpha 1-Antitrypsin Deficiency", "descriptor_ui": "D019896", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "DNA Transposable Elements", "descriptor_ui": "D004251", "major_topic": false }, { "descriptor": "Hepatocytes", "descriptor_ui": "D022781", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Induced Pluripotent Stem Cells", "descriptor_ui": "D057026", "major_topic": false }, { "descriptor": "Liver", "descriptor_ui": "D008099", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Serum Albumin", "descriptor_ui": "D012709", "major_topic": false }, { "descriptor": "Serum Albumin, Human", "descriptor_ui": "D000075462", "major_topic": false }, { "descriptor": "Targeted Gene Repair", "descriptor_ui": "D052416", "major_topic": true }, { "descriptor": "Time Factors", "descriptor_ui": "D013997", "major_topic": false } ], "publication": { "conference_name": null, "date": "2011 Oct 12", "date_precision": "day", "issue": "7369", "normalized_date": "2011-10-12", "pages": "391-394", "proceedings_title": null, "publisher": "", "title": "Nature", "volume": "478", "year": 2011 }, "ssbd": { "database": [], "repository": [] }, "title": "Targeted gene correction of alpha1-antitrypsin deficiency in induced pluripotent stem cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Optical methods for viewing neuronal populations and projections in the intact mammalian brain are needed, but light scattering prevents imaging deep into brain structures. We imaged fixed brain tissue using Scale, an aqueous reagent that renders biological samples optically transparent but completely preserves fluorescent signals in the clarified structures. In Scale-treated mouse brain, neurons labeled with genetically encoded fluorescent proteins were visualized at an unprecedented depth in millimeter-scale networks and at subcellular resolution. The improved depth and scale of imaging permitted comprehensive three-dimensional reconstructions of cortical, callosal and hippocampal projections whose extent was limited only by the working distance of the objective lenses. In the intact neurogenic niche of the dentate gyrus, Scale allowed the quantitation of distances of neural stem cells to blood vessels. Our findings suggest that the Scale method will be useful for light microscopy-based connectomics of cellular networks in brain and other tissues.", "classifications": [ { "id": "Sawano", "label": "Group Sawano", "parent": "Shintaku", "type": "group" }, { "id": "Shintaku", "label": "Team Shintaku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Hama", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Kurokawa", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Kawano", "name": null }, { "creator_type": "author", "first_name": "Ryoko", "last_name": "Ando", "name": null }, { "creator_type": "author", "first_name": "Tomomi", "last_name": "Shimogori", "name": null }, { "creator_type": "author", "first_name": "Hisayori", "last_name": "Noda", "name": null }, { "creator_type": "author", "first_name": "Kiyoko", "last_name": "Fukami", "name": null }, { "creator_type": "author", "first_name": "Asako", "last_name": "Sakaue-Sawano", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Miyawaki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/nn.2928" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "21878933" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Animals, Newborn", "descriptor_ui": "D000831", "major_topic": false }, { "descriptor": "Brain", "descriptor_ui": "D001921", "major_topic": false }, { "descriptor": "Cell Proliferation", "descriptor_ui": "D049109", "major_topic": false }, { "descriptor": "Embryo, Mammalian", "descriptor_ui": "D004622", "major_topic": false }, { "descriptor": "Glycerol", "descriptor_ui": "D005990", "major_topic": false }, { "descriptor": "Imaging, Three-Dimensional", "descriptor_ui": "D021621", "major_topic": false }, { "descriptor": "Intermediate Filament Proteins", "descriptor_ui": "D007381", "major_topic": false }, { "descriptor": "Luminescent Proteins", "descriptor_ui": "D008164", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Transgenic", "descriptor_ui": "D008822", "major_topic": false }, { "descriptor": "Microscopy, Fluorescence", "descriptor_ui": "D008856", "major_topic": false }, { "descriptor": "Nerve Tissue Proteins", "descriptor_ui": "D009419", "major_topic": false }, { "descriptor": "Nestin", "descriptor_ui": "D064231", "major_topic": false }, { "descriptor": "Neural Cell Adhesion Molecule L1", "descriptor_ui": "D039842", "major_topic": false }, { "descriptor": "Neural Stem Cells", "descriptor_ui": "D058953", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Octoxynol", "descriptor_ui": "D017830", "major_topic": false }, { "descriptor": "Receptors, AMPA", "descriptor_ui": "D018091", "major_topic": false }, { "descriptor": "Sialic Acids", "descriptor_ui": "D012794", "major_topic": false }, { "descriptor": "Synaptophysin", "descriptor_ui": "D016708", "major_topic": false }, { "descriptor": "Thy-1 Antigens", "descriptor_ui": "D018800", "major_topic": false }, { "descriptor": "Time Factors", "descriptor_ui": "D013997", "major_topic": false }, { "descriptor": "Tissue Fixation", "descriptor_ui": "D016707", "major_topic": false }, { "descriptor": "Urea", "descriptor_ui": "D014508", "major_topic": false } ], "publication": { "conference_name": null, "date": "2011 Aug 30", "date_precision": "day", "issue": "11", "normalized_date": "2011-08-30", "pages": "1481-1488", "proceedings_title": null, "publisher": "", "title": "Nature neuroscience", "volume": "14", "year": 2011 }, "ssbd": { "database": [], "repository": [] }, "title": "Scale: a chemical approach for fluorescence imaging and reconstruction of transparent mouse brain.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Lipid giant vesicles (GVs) exhibit biologically relevant morphological dynamics such as growth and division under certain conditions without any sophisticated molecular machineries employed by the current organisms. Nonequilibrium conditions are essential for the emergence of dynamic behaviors, which are normally generated by the addition of stimulating materials or by the change of some physical conditions. Therefore, an experimental method that allows flexible control of external conditions is desirable. Here we report a new and simple perfusion device for light microscopy observation that simultaneously realizes such control and tracking of individual phospholipid GVs for the long-term. We apply this device to the study of the morphological dynamics of POPC-based giant multilamellar vesicles (GMVs) under a monotonic and gradual increase of surfactant concentration; thereby we reveal the existence of multiple pathways in the slow solubilization processes, whose frequencies depend on the compositions of GMVs. This perfusion device would offer an unprecedented control of external conditions in the studies of GVs and might help us characterize the physicochemical origins of rich morphological dynamics of living cells.", "classifications": [ { "id": "Wakamoto", "label": "Group Wakamoto", "parent": "Wakamoto", "type": "group" }, { "id": "Wakamoto", "label": "Team Wakamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Takuya", "last_name": "Tomita", "name": null }, { "creator_type": "author", "first_name": "Tadashi", "last_name": "Sugawara", "name": null }, { "creator_type": "author", "first_name": "Yuichi", "last_name": "Wakamoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/la2018456" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "21702436" } }, "mesh": [ { "descriptor": "Liposomes", "descriptor_ui": "D008081", "major_topic": false }, { "descriptor": "Microscopy, Phase-Contrast", "descriptor_ui": "D008858", "major_topic": false }, { "descriptor": "Phosphatidylcholines", "descriptor_ui": "D010713", "major_topic": false } ], "publication": { "conference_name": null, "date": "2011 Aug 16", "date_precision": "day", "issue": "16", "normalized_date": "2011-08-16", "pages": "10106-10112", "proceedings_title": null, "publisher": "", "title": "Langmuir : the ACS journal of surfaces and colloids", "volume": "27", "year": 2011 }, "ssbd": { "database": [], "repository": [] }, "title": "Multitude of morphological dynamics of giant multilamellar vesicles in regulated nonequilibrium environments.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "This study was performed to understand the anatomical substrates for Kolliker-Fuse nucleus (KFN) modulation of respiratory-related tongue movement. After application of cholera toxin B subunit (CTb) to the medial branch of the hypoglossal nerve (HGn) and injection of biotinylated dextran amine (BDA) into the KFN ipsilaterally, an overlapping distribution of BDA-labeled axon terminals and CTb-labeled neurons was found in the ventral compartment of the hypoglossal nucleus (HGN) ipsilateral to the application and injection sites. At the electron microscopic level, the BDA-labeled terminals made asymmetrical synaptic contacts predominantly with dendrites of the HGN neurons, some of which were labeled with CTb. Using retrograde tracing combined with in situ hybridization, we demonstrated that almost all the KFN neurons sending their axons to the HGN were positive for vesicular glutamate transporter (VGLUT) 2 mRNA but not glutamic acid decarboxylase 67 mRNA. Using a combination of anterograde and retrograde tracing techniques and immunohistochemistry for VGLUT2, we further demonstrated that the KFN axon terminals with VGLUT2 immunoreactivity established close contact with the HGN motoneurons whose axons constitute the medial branch of the HGn. The present results suggest that glutamatergic KFN fibers may exert excitatory influence upon the HGN motoneurons sending their axons to the medial branch of the HGn for the control of protruder tongue muscles contraction to maintain airway patency during respiration.", "classifications": [ { "id": "Yokota", "label": "Group Yokota", "parent": "Enomoto", "type": "group" }, { "id": "Enomoto", "label": "Team Enomoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Shigefumi", "last_name": "Yokota", "name": null }, { "creator_type": "author", "first_name": "Jian-Guo", "last_name": "Niu", "name": null }, { "creator_type": "author", "first_name": "Toshiko", "last_name": "Tsumori", "name": null }, { "creator_type": "author", "first_name": "Tatsuro", "last_name": "Oka", "name": null }, { "creator_type": "author", "first_name": "Yukihiko", "last_name": "Yasui", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.brainres.2011.06.025" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "21724177" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Axons", "descriptor_ui": "D001369", "major_topic": false }, { "descriptor": "Biotin", "descriptor_ui": "D001710", "major_topic": false }, { "descriptor": "Cholera Toxin", "descriptor_ui": "D002772", "major_topic": false }, { "descriptor": "Dextrans", "descriptor_ui": "D003911", "major_topic": false }, { "descriptor": "Glutamate Decarboxylase", "descriptor_ui": "D005968", "major_topic": false }, { "descriptor": "Glutamic Acid", "descriptor_ui": "D018698", "major_topic": false }, { "descriptor": "Hypoglossal Nerve", "descriptor_ui": "D007002", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Medulla Oblongata", "descriptor_ui": "D008526", "major_topic": false }, { "descriptor": "Microscopy, Electron", "descriptor_ui": "D008854", "major_topic": false }, { "descriptor": "Motor Neurons", "descriptor_ui": "D009046", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Pons", "descriptor_ui": "D011149", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Rats, Wistar", "descriptor_ui": "D017208", "major_topic": false }, { "descriptor": "RNA, Messenger", "descriptor_ui": "D012333", "major_topic": false }, { "descriptor": "Vesicular Glutamate Transport Protein 2", "descriptor_ui": "D050599", "major_topic": false } ], "publication": { "conference_name": null, "date": "2011 Aug 2", "date_precision": "day", "issue": "", "normalized_date": "2011-08-02", "pages": "10-20", "proceedings_title": null, "publisher": "", "title": "Brain research", "volume": "1404", "year": 2011 }, "ssbd": { "database": [], "repository": [] }, "title": "Glutamatergic Kolliker-Fuse nucleus neurons innervate hypoglossal motoneurons whose axons form the medial (protruder) branch of the hypoglossal nerve in the rat.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Angiotensin II (Ang II) is a major vasoactive peptide of the renin-angiotensin system. Ang II is originally found as one of potent vasoconstrictors, but is now attracted attention as an essential mediator of many cardiovascular problems, including endothelial dysfunction, arrhythmia and structural remodeling of cardiovascular systems. Most of the known pathophysiological effects of Ang II are mediated through Ang type1 receptors (AT(1)Rs), and the up-regulation of AT(1)Rs is one of important causes by which Ang II can contribute to cardiovascular diseases. A growing body of evidence has suggested that reactive oxygen species (ROS) and reactive nitrogen species (RNS) play important roles in the regulation of AT(1)R signaling. In cardiac fibroblasts, stimulation with cytokines or bacterial toxins induces AT(1)R up-regulation through NADPH oxidase-dependent ROS production. In contrast, nitric oxide (NO) decreases AT(1)R density through cysteine modification (S-nitrosylation) of a transcriptional factor, nuclear factor kappaB (NF-kappaB). The difference between the effects of ROS and NO on AT(1)R expression may be caused by the difference between intracellular location of ROS signaling and that of NO signaling, as the agonist-induced S-nitrosylation of NF-kappaB requires a local interaction between NO synthase (NOS) and NF-kappaB in the perinuclear region. Thus, the spatial and temporal regulation of cysteine modification by ROS or RNS may underlie the resultant changes of AT(1)R signaling induced by agonist stimulation.", "classifications": [ { "id": "Nishida", "label": "Group Nishida", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Motohiro", "last_name": "Nishida", "name": null }, { "creator_type": "author", "first_name": "Naoyuki", "last_name": "Kitajima", "name": null }, { "creator_type": "author", "first_name": "Shota", "last_name": "Saiki", "name": null }, { "creator_type": "author", "first_name": "Michio", "last_name": "Nakaya", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Kurose", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.niox.2010.10.003" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "21078404" } }, "mesh": [ { "descriptor": "Angiotensin II", "descriptor_ui": "D000804", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cysteine", "descriptor_ui": "D003545", "major_topic": false }, { "descriptor": "Fibroblasts", "descriptor_ui": "D005347", "major_topic": false }, { "descriptor": "Gene Expression Regulation", "descriptor_ui": "D005786", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Nitric Oxide", "descriptor_ui": "D009569", "major_topic": false }, { "descriptor": "Nitric Oxide Synthase Type II", "descriptor_ui": "D052247", "major_topic": false }, { "descriptor": "Oxidation-Reduction", "descriptor_ui": "D010084", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Reactive Oxygen Species", "descriptor_ui": "D017382", "major_topic": false }, { "descriptor": "Receptors, Angiotensin", "descriptor_ui": "D011945", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": true }, { "descriptor": "Transcription Factor RelA", "descriptor_ui": "D051996", "major_topic": false }, { "descriptor": "Up-Regulation", "descriptor_ui": "D015854", "major_topic": false } ], "publication": { "conference_name": null, "date": "2011 Aug 1", "date_precision": "day", "issue": "2", "normalized_date": "2011-08-01", "pages": "112-117", "proceedings_title": null, "publisher": "", "title": "Nitric oxide : biology and chemistry", "volume": "25", "year": 2011 }, "ssbd": { "database": [], "repository": [] }, "title": "Regulation of Angiotensin II receptor signaling by cysteine modification of NF-kappaB.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Selective activation of p53 target genes in response to various cellular stresses is a critical step in determining the ability to induce cell-cycle arrest or apoptosis. Here we report the identification of the microRNA miR-22 as a p53 target gene that selectively determines the induction of p53-dependent apoptosis by repressing p21. Combinatorial analyses of the AGO2 immunocomplex and gene expression profiles identified p21 as a direct target of miR-22. Induction of p21 was inhibited by miR-22 after exposure to the genotoxic agent Adriamycin (doxorubicin; Bedford Laboratories), sensitizing cells to p53-dependent apoptosis. Interestingly, the activation of miR-22 depended on the intensity of the stresses that induced cells to undergo apoptosis in the presence of p21 suppression. Our findings define an intrinsic molecular switch that determines p53-dependent cellular fate through post-transcriptional regulation of p21.", "classifications": [ { "id": "Okamoto", "label": "Group Okamoto", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Naoto", "last_name": "Tsuchiya", "name": null }, { "creator_type": "author", "first_name": "Masashi", "last_name": "Izumiya", "name": null }, { "creator_type": "author", "first_name": "Hiroko", "last_name": "Ogata-Kawata", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Okamoto", "name": null }, { "creator_type": "author", "first_name": "Yuko", "last_name": "Fujiwara", "name": null }, { "creator_type": "author", "first_name": "Makiko", "last_name": "Nakai", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Okabe", "name": null }, { "creator_type": "author", "first_name": "Aaron J.", "last_name": "Schetter", "name": null }, { "creator_type": "author", "first_name": "Elise D.", "last_name": "Bowman", "name": null }, { "creator_type": "author", "first_name": "Yutaka", "last_name": "Midorikawa", "name": null }, { "creator_type": "author", "first_name": "Yasuyuki", "last_name": "Sugiyama", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Aburatani", "name": null }, { "creator_type": "author", "first_name": "Curtis C.", "last_name": "Harris", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Nakagama", "name": null } ], "identifiers": { "doi": { "normalized": "10.1158/0008-5472.can-10-2475" }, "pmcid": { "normalized": "PMC7425979" }, "pmid": { "normalized": "21565979" } }, "mesh": [ { "descriptor": "Apoptosis", "descriptor_ui": "D017209", "major_topic": false }, { "descriptor": "Base Sequence", "descriptor_ui": "D001483", "major_topic": false }, { "descriptor": "Colonic Neoplasms", "descriptor_ui": "D003110", "major_topic": false }, { "descriptor": "Cyclin-Dependent Kinase Inhibitor p21", "descriptor_ui": "D050759", "major_topic": false }, { "descriptor": "Genes, Tumor Suppressor", "descriptor_ui": "D016147", "major_topic": true }, { "descriptor": "Genomics", "descriptor_ui": "D023281", "major_topic": false }, { "descriptor": "HCT116 Cells", "descriptor_ui": "D045325", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "MicroRNAs", "descriptor_ui": "D035683", "major_topic": false }, { "descriptor": "Molecular Sequence Data", "descriptor_ui": "D008969", "major_topic": false }, { "descriptor": "Transcription, Genetic", "descriptor_ui": "D014158", "major_topic": false }, { "descriptor": "Transcriptional Activation", "descriptor_ui": "D015533", "major_topic": false }, { "descriptor": "Tumor Suppressor Protein p53", "descriptor_ui": "D016159", "major_topic": false } ], "publication": { "conference_name": null, "date": "2011 Jul 1", "date_precision": "day", "issue": "13", "normalized_date": "2011-07-01", "pages": "4628-4639", "proceedings_title": null, "publisher": "", "title": "Cancer research", "volume": "71", "year": 2011 }, "ssbd": { "database": [], "repository": [] }, "title": "Tumor suppressor miR-22 determines p53-dependent cellular fate through post-transcriptional regulation of p21.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "We report the use of fluorescent nanodiamonds (FNDs) as a photostable fluorescent probe for high resolution saturated excitation (SAX) microscopy. We confirmed that FNDs show a nonlinear fluorescence response under saturated excitation conditions generated by intense excitation light. Using FNDs, we quantified the spatial resolution improvement inherent in SAX microscopy, and experimentally demonstrated the scalability of the spatial resolution of SAX microscopy. The photostability of the FNDs allowed us to perform nanoparticle imaging of a multicolor-stained macrophage cell with a spatial resolution beyond the diffraction limit.", "classifications": [ { "id": "Fujita", "label": "Group Fujita", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Masahito", "last_name": "Yamanaka", "name": null }, { "creator_type": "author", "first_name": "Yan-Kai", "last_name": "Tzeng", "name": null }, { "creator_type": "author", "first_name": "Shogo", "last_name": "Kawano", "name": null }, { "creator_type": "author", "first_name": "Nicholas I.", "last_name": "Smith", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Kawata", "name": null }, { "creator_type": "author", "first_name": "Huan-Cheng", "last_name": "Chang", "name": null }, { "creator_type": "author", "first_name": "Katsumasa", "last_name": "Fujita", "name": null } ], "identifiers": { "doi": { "normalized": "10.1364/boe.2.001946" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "21750771" } }, "mesh": [], "publication": { "conference_name": null, "date": "2011 Jul 01", "date_precision": "day", "issue": "7", "normalized_date": "2011-07-01", "pages": "1946-1954", "proceedings_title": null, "publisher": "", "title": "Biomedical Optics Express", "volume": "2", "year": 2011 }, "ssbd": { "database": [], "repository": [] }, "title": "SAX microscopy with fluorescent nanodiamond probes for high-resolution fluorescence imaging.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The emphasis in anticancer drug discovery has always been on finding a drug with great antitumor potential but few side-effects. This can be achieved if the drug is specific for a molecular site found only in tumor cells. Here, we find the enhancer of zeste homolog 2 (EZH2) to be highly overexpressed in lung and other cancers, and show that EZH2 is integral to proliferation in cancer cells. Quantitative real-time PCR analysis revealed higher expression of EZH2 in clinical bladder cancer tissues than in corresponding non-neoplastic tissues (P < 0.0001), and we confirmed that a wide range of cancers also overexpress EZH2, using cDNA microarray analysis. Immunohistochemical analysis showed positive staining for EZH2 in 14 of 29 cases of bladder cancer, 135 of 292 cases of non-small-cell lung cancer (NSCLC), and 214 of 245 cases of colorectal cancer, whereas no significant staining was observed in various normal tissues. We found elevated expression of EZH2 to be associated with poor prognosis for patients with NSCLC (P = 0.0239). In lung and bladder cancer cells overexpressing EZH2, suppression of EZH2 using specific siRNAs inhibited incorporation of BrdU and resulted in significant suppression of cell growth, even though no significant effect was observed in the normal cell strain CCD-18Co, which has undetectable EZH2. Because EZH2 expression was scarcely detectable in all normal tissues we examined, EZH2 shows promise as a tumor-specific therapeutic target. Furthermore, as elevated levels of EZH2 are associated with poor prognosis of patients with NSCLC, its overexpression in resected specimens could prove a useful molecular marker, indicating the necessity for a more extensive follow-up in some lung cancer patients after surgical treatment.", "classifications": [ { "id": "Hamamoto", "label": "Group Hamamoto", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Masashi", "last_name": "Takawa", "name": null }, { "creator_type": "author", "first_name": "Ken", "last_name": "Masuda", "name": null }, { "creator_type": "author", "first_name": "Masaki", "last_name": "Kunizaki", "name": null }, { "creator_type": "author", "first_name": "Yataro", "last_name": "Daigo", "name": null }, { "creator_type": "author", "first_name": "Katsunori", "last_name": "Takagi", "name": null }, { "creator_type": "author", "first_name": "Yukiko", "last_name": "Iwai", "name": null }, { "creator_type": "author", "first_name": "Hyun-Soo", "last_name": "Cho", "name": null }, { "creator_type": "author", "first_name": "Gouji", "last_name": "Toyokawa", "name": null }, { "creator_type": "author", "first_name": "Yuka", "last_name": "Yamane", "name": null }, { "creator_type": "author", "first_name": "Kazuhiro", "last_name": "Maejima", "name": null }, { "creator_type": "author", "first_name": "Helen I.", "last_name": "Field", "name": null }, { "creator_type": "author", "first_name": "Takaaki", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Takayuki", "last_name": "Akasu", "name": null }, { "creator_type": "author", "first_name": "Masanori", "last_name": "Sugiyama", "name": null }, { "creator_type": "author", "first_name": "Eijyu", "last_name": "Tsuchiya", "name": null }, { "creator_type": "author", "first_name": "Yutaka", "last_name": "Atomi", "name": null }, { "creator_type": "author", "first_name": "Bruce A. J.", "last_name": "Ponder", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Ryuji", "last_name": "Hamamoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/j.1349-7006.2011.01958.x" }, "pmcid": { "normalized": "PMC11159278" }, "pmid": { "normalized": "21539681" } }, "mesh": [ { "descriptor": "Adolescent", "descriptor_ui": "D000293", "major_topic": false }, { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Aged, 80 and over", "descriptor_ui": "D000369", "major_topic": false }, { "descriptor": "Biomarkers, Tumor", "descriptor_ui": "D014408", "major_topic": false }, { "descriptor": "Cell Proliferation", "descriptor_ui": "D049109", "major_topic": false }, { "descriptor": "Colorectal Neoplasms", "descriptor_ui": "D015179", "major_topic": false }, { "descriptor": "DNA-Binding Proteins", "descriptor_ui": "D004268", "major_topic": false }, { "descriptor": "Enhancer of Zeste Homolog 2 Protein", "descriptor_ui": "D000071221", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Lung Neoplasms", "descriptor_ui": "D008175", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Neoplasms", "descriptor_ui": "D009369", "major_topic": false }, { "descriptor": "Polycomb Repressive Complex 2", "descriptor_ui": "D063151", "major_topic": false }, { "descriptor": "Prognosis", "descriptor_ui": "D011379", "major_topic": false }, { "descriptor": "Proportional Hazards Models", "descriptor_ui": "D016016", "major_topic": false }, { "descriptor": "Transcription Factors", "descriptor_ui": "D014157", "major_topic": false }, { "descriptor": "Urinary Bladder Neoplasms", "descriptor_ui": "D001749", "major_topic": false } ], "publication": { "conference_name": null, "date": "2011-07", "date_precision": "month", "issue": "7", "normalized_date": "2011-07", "pages": "1298-1305", "proceedings_title": null, "publisher": "", "title": "Cancer Science", "volume": "102", "year": 2011 }, "ssbd": { "database": [], "repository": [] }, "title": "Validation of the histone methyltransferase EZH2 as a therapeutic target for various types of human cancer and as a prognostic marker", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Biological applications where nanoparticles are used in a cell environment with laser irradiation are rapidly emerging. Investigation of the localized heating effect due to the laser irradiation on the particle is required to preclude unintended thermal effects. While bulk temperature rise can be determined using macroscale measurement methods, observation of the actual temperature within the nanoscale domain around the particle is difficult and here we propose a method to measure the local temperature around a single gold nanoparticle in liquid, using white light scattering spectroscopy. Using 40-nm-diameter gold nanoparticles coated with thermo-responsive polymer, we monitored the localized heating effect through the plasmon peak shift. The shift occurs due to the temperature-dependent refractive index change in surrounding polymer medium. The results indicate that the particle experiences a temperature rise of around 10 degrees Celsius when irradiated with tightly focused irradiation of ~1 mW at 532 nm.", "classifications": [ { "id": "Fujita", "label": "Group Fujita", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Mitsuhiro", "last_name": "Honda", "name": null }, { "creator_type": "author", "first_name": "Yuika", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Nicholas I.", "last_name": "Smith", "name": null }, { "creator_type": "author", "first_name": "Katsumasa", "last_name": "Fujita", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Kawata", "name": null } ], "identifiers": { "doi": { "normalized": "10.1364/oe.19.012375" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "21716475" } }, "mesh": [ { "descriptor": "Acrylamides", "descriptor_ui": "D000178", "major_topic": false }, { "descriptor": "Acrylic Resins", "descriptor_ui": "D000180", "major_topic": false }, { "descriptor": "Cell Biology", "descriptor_ui": "D003585", "major_topic": false }, { "descriptor": "Equipment Design", "descriptor_ui": "D004867", "major_topic": false }, { "descriptor": "Gold", "descriptor_ui": "D006046", "major_topic": false }, { "descriptor": "Hot Temperature", "descriptor_ui": "D006358", "major_topic": true }, { "descriptor": "Lasers", "descriptor_ui": "D007834", "major_topic": true }, { "descriptor": "Light", "descriptor_ui": "D008027", "major_topic": false }, { "descriptor": "Microscopy", "descriptor_ui": "D008853", "major_topic": false }, { "descriptor": "Models, Theoretical", "descriptor_ui": "D008962", "major_topic": false }, { "descriptor": "Nanoparticles", "descriptor_ui": "D053758", "major_topic": true }, { "descriptor": "Nanotechnology", "descriptor_ui": "D036103", "major_topic": false }, { "descriptor": "Polymers", "descriptor_ui": "D011108", "major_topic": false }, { "descriptor": "Refractometry", "descriptor_ui": "D012031", "major_topic": false }, { "descriptor": "Scattering, Radiation", "descriptor_ui": "D012542", "major_topic": false }, { "descriptor": "Surface Plasmon Resonance", "descriptor_ui": "D020349", "major_topic": false }, { "descriptor": "Ultraviolet Rays", "descriptor_ui": "D014466", "major_topic": false } ], "publication": { "conference_name": null, "date": "2011 Jun 20", "date_precision": "day", "issue": "13", "normalized_date": "2011-06-20", "pages": "12375-12383", "proceedings_title": null, "publisher": "", "title": "Optics express", "volume": "19", "year": 2011 }, "ssbd": { "database": [], "repository": [] }, "title": "Nanoscale heating of laser irradiated single gold nanoparticles in liquid.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Novel types of PKCalpha activators based on isobenzofuranone bearing a myo-inositol moiety were designed and synthesized. The derivatives with bulky substituents on the myo-inositol moiety significantly activated PKCalpha, but their binding sites were not the same as that of phorbol ester.", "classifications": [ { "id": "Sodeoka", "label": "Group Sodeoka", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Go", "last_name": "Hirai", "name": null }, { "creator_type": "author", "first_name": "Megumi", "last_name": "Ohkubo", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Tamura", "name": null }, { "creator_type": "author", "first_name": "Mikiko", "last_name": "Sodeoka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.bmcl.2011.04.108" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "21596562" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Binding Sites", "descriptor_ui": "D001665", "major_topic": false }, { "descriptor": "Drug Design", "descriptor_ui": "D015195", "major_topic": true }, { "descriptor": "Enzyme Activation", "descriptor_ui": "D004789", "major_topic": false }, { "descriptor": "Enzyme Activators", "descriptor_ui": "D020536", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Models, Biological", "descriptor_ui": "D008954", "major_topic": false }, { "descriptor": "Molecular Structure", "descriptor_ui": "D015394", "major_topic": false }, { "descriptor": "Phorbol Esters", "descriptor_ui": "D010703", "major_topic": false }, { "descriptor": "Protein Binding", "descriptor_ui": "D011485", "major_topic": false }, { "descriptor": "Protein Kinase C-alpha", "descriptor_ui": "D051571", "major_topic": false } ], "publication": { "conference_name": null, "date": "2011 Jun 15", "date_precision": "day", "issue": "12", "normalized_date": "2011-06-15", "pages": "3587-3590", "proceedings_title": null, "publisher": "", "title": "Bioorganic & medicinal chemistry letters", "volume": "21", "year": 2011 }, "ssbd": { "database": [], "repository": [] }, "title": "Design and synthesis of protein kinase Calpha activators based on 'out of pocket' interactions.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The biological function of noise-induced symmetry breaking (NISB) is still unclear even though it may potentially occur in noisy intracellular systems. In this work, I demonstrate that information decoding from a noisy signal is a potential biological function of NISB by revealing that NISB naturally emerges from an optimal information-decoding dynamics and that several intracellular networks can be identified with the information-decoding dynamics. I also propose a mean first passage time profile as a way to experimentally identify NISB.", "classifications": [ { "id": "Kobayashi", "label": "Group Kobayashi", "parent": "Wakamoto", "type": "group" }, { "id": "Wakamoto", "label": "Team Wakamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Tetsuya J.", "last_name": "Kobayashi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1103/physrevlett.106.228101" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "21702634" } }, "mesh": [ { "descriptor": "Intracellular Space", "descriptor_ui": "D042541", "major_topic": false }, { "descriptor": "Models, Biological", "descriptor_ui": "D008954", "major_topic": true }, { "descriptor": "T-Lymphocytes", "descriptor_ui": "D013601", "major_topic": false } ], "publication": { "conference_name": null, "date": "2011 Jun 3", "date_precision": "day", "issue": "22", "normalized_date": "2011-06-03", "pages": "228101", "proceedings_title": null, "publisher": "", "title": "Physical review letters", "volume": "106", "year": 2011 }, "ssbd": { "database": [], "repository": [] }, "title": "Connection between noise-induced symmetry breaking and an information-decoding function for intracellular networks.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: The research emphasis in anti-cancer drug discovery has always been to search for a drug with the greatest antitumor potential but fewest side effects. This can only be achieved if the drug used is against a specific target located in the tumor cells. In this study, we evaluated Minichromosome Maintenance Protein 7 (MCM7) as a novel therapeutic target in cancer. RESULTS: Immunohistochemical analysis showed that MCM7 was positively stained in 196 of 331 non-small cell lung cancer (NSCLC), 21 of 29 bladder tumor and 25 of 70 liver tumor cases whereas no significant staining was observed in various normal tissues. We also found an elevated expression of MCM7 to be associated with poor prognosis for patients with NSCLC (P = 0.0055). qRT-PCR revealed a higher expression of MCM7 in clinical bladder cancer tissues than in corresponding non-neoplastic tissues (P < 0.0001), and we confirmed that a wide range of cancers also overexpressed MCM7 by cDNA microarray analysis. Suppression of MCM7 using specific siRNAs inhibited incorporation of BrdU in lung and bladder cancer cells overexpressing MCM7, and suppressed the growth of those cells more efficiently than that of normal cell strains expressing lower levels of MCM7. CONCLUSIONS: Since MCM7 expression was generally low in a number of normal tissues we examined, MCM7 has the characteristics of an ideal candidate for molecular targeted cancer therapy in various tumors and also as a good prognostic biomarker for NSCLC patients.", "classifications": [ { "id": "Hamamoto", "label": "Group Hamamoto", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Gouji", "last_name": "Toyokawa", "name": null }, { "creator_type": "author", "first_name": "Ken", "last_name": "Masuda", "name": null }, { "creator_type": "author", "first_name": "Yataro", "last_name": "Daigo", "name": null }, { "creator_type": "author", "first_name": "Hyun-Soo", "last_name": "Cho", "name": null }, { "creator_type": "author", "first_name": "Masanori", "last_name": "Yoshimatsu", "name": null }, { "creator_type": "author", "first_name": "Masashi", "last_name": "Takawa", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Hayami", "name": null }, { "creator_type": "author", "first_name": "Kazuhiro", "last_name": "Maejima", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Chino", "name": null }, { "creator_type": "author", "first_name": "Helen I.", "last_name": "Field", "name": null }, { "creator_type": "author", "first_name": "David E.", "last_name": "Neal", "name": null }, { "creator_type": "author", "first_name": "Eiju", "last_name": "Tsuchiya", "name": null }, { "creator_type": "author", "first_name": "Bruce A. J.", "last_name": "Ponder", "name": null }, { "creator_type": "author", "first_name": "Yoshihiko", "last_name": "Maehara", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Ryuji", "last_name": "Hamamoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1186/1476-4598-10-65" }, "pmcid": { "normalized": "PMC3125391" }, "pmid": { "normalized": "21619671" } }, "mesh": [ { "descriptor": "Biomarkers, Tumor", "descriptor_ui": "D014408", "major_topic": true }, { "descriptor": "Carcinoma, Non-Small-Cell Lung", "descriptor_ui": "D002289", "major_topic": false }, { "descriptor": "Cell Cycle Proteins", "descriptor_ui": "D018797", "major_topic": false }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Cell Proliferation", "descriptor_ui": "D049109", "major_topic": false }, { "descriptor": "DNA-Binding Proteins", "descriptor_ui": "D004268", "major_topic": false }, { "descriptor": "Gene Expression Profiling", "descriptor_ui": "D020869", "major_topic": false }, { "descriptor": "Gene Expression Regulation, Neoplastic", "descriptor_ui": "D015972", "major_topic": true }, { "descriptor": "Gene Silencing", "descriptor_ui": "D020868", "major_topic": false }, { "descriptor": "HCT116 Cells", "descriptor_ui": "D045325", "major_topic": false }, { "descriptor": "HEK293 Cells", "descriptor_ui": "D057809", "major_topic": false }, { "descriptor": "HeLa Cells", "descriptor_ui": "D006367", "major_topic": false }, { "descriptor": "Hep G2 Cells", "descriptor_ui": "D056945", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Lung Neoplasms", "descriptor_ui": "D008175", "major_topic": false }, { "descriptor": "Minichromosome Maintenance Complex Component 7", "descriptor_ui": "D064168", "major_topic": false }, { "descriptor": "Neoplasms", "descriptor_ui": "D009369", "major_topic": false }, { "descriptor": "Nuclear Proteins", "descriptor_ui": "D009687", "major_topic": false }, { "descriptor": "Prognosis", "descriptor_ui": "D011379", "major_topic": false }, { "descriptor": "Protein Binding", "descriptor_ui": "D011485", "major_topic": false }, { "descriptor": "Protein-Arginine N-Methyltransferases", "descriptor_ui": "D011484", "major_topic": false }, { "descriptor": "RNA, Small Interfering", "descriptor_ui": "D034741", "major_topic": false } ], "publication": { "conference_name": null, "date": "2011 May 28", "date_precision": "day", "issue": "", "normalized_date": "2011-05-28", "pages": "65", "proceedings_title": null, "publisher": "", "title": "Molecular cancer", "volume": "10", "year": 2011 }, "ssbd": { "database": [], "repository": [] }, "title": "Minichromosome Maintenance Protein 7 is a potential therapeutic target in human cancer and a novel prognostic marker of non-small cell lung cancer.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Dilated cardiomyopathy (DCM) is a myocardial disorder that is characterized by dilation and dysfunction of the left ventricle (LV). Accumulating evidence has implicated aberrant Ca(2+) signaling and oxidative stress in the progression of DCM, but the molecular details are unknown. In the present study, we report that inhibition of the transient receptor potential canonical 3 (TRPC3) channels partially prevents LV dilation and dysfunction in muscle LIM protein-deficient (MLP (-/-)) mice, a murine model of DCM. The expression level of TRPC3 and the activity of Ca(2+)/calmodulin-dependent kinase II (CaMKII) were increased in MLP (-/-) mouse hearts. Acitivity of Rac1, a small GTP-binding protein that participates in NADPH oxidase (Nox) activation, and the production of reactive oxygen species (ROS) were also increased in MLP (-/-) mouse hearts. Treatment with pyrazole-3, a TRPC3 selective inhibitor, strongly suppressed the increased activities of CaMKII and Rac1, as well as ROS production. In contrast, activation of TRPC3 by 1-oleoyl-2-acetyl-sn-glycerol (OAG), or by mechanical stretch, induced ROS production in rat neonatal cardiomyocytes. These results suggest that up-regulation of TRPC3 is responsible for the increase in CaMKII activity and the Nox-mediated ROS production in MLP (-/-) mouse cardiomyocytes, and that inhibition of TRPC3 is an effective therapeutic strategy to prevent the progression of DCM.", "classifications": [ { "id": "Nishida", "label": "Group Nishida", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Naoyuki", "last_name": "Kitajima", "name": null }, { "creator_type": "author", "first_name": "Kunihiro", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Sachio", "last_name": "Morimoto", "name": null }, { "creator_type": "author", "first_name": "Yoji", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Shigeki", "last_name": "Kiyonaka", "name": null }, { "creator_type": "author", "first_name": "Masahiko", "last_name": "Hoshijima", "name": null }, { "creator_type": "author", "first_name": "Yasuhiro", "last_name": "Ikeda", "name": null }, { "creator_type": "author", "first_name": "Michio", "last_name": "Nakaya", "name": null }, { "creator_type": "author", "first_name": "Tomomi", "last_name": "Ide", "name": null }, { "creator_type": "author", "first_name": "Yasuo", "last_name": "Mori", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Kurose", "name": null }, { "creator_type": "author", "first_name": "Motohiro", "last_name": "Nishida", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.bbrc.2011.04.124" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "21565173" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Calcium", "descriptor_ui": "D002118", "major_topic": false }, { "descriptor": "Calcium-Calmodulin-Dependent Protein Kinase Type 2", "descriptor_ui": "D054732", "major_topic": false }, { "descriptor": "Cardiomyopathy, Dilated", "descriptor_ui": "D002311", "major_topic": false }, { "descriptor": "LIM Domain Proteins", "descriptor_ui": "D060588", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Mutant Strains", "descriptor_ui": "D008817", "major_topic": false }, { "descriptor": "Muscle Proteins", "descriptor_ui": "D009124", "major_topic": false }, { "descriptor": "Myocardium", "descriptor_ui": "D009206", "major_topic": false }, { "descriptor": "Neuropeptides", "descriptor_ui": "D009479", "major_topic": false }, { "descriptor": "Pyrazoles", "descriptor_ui": "D011720", "major_topic": false }, { "descriptor": "rac GTP-Binding Proteins", "descriptor_ui": "D020744", "major_topic": false }, { "descriptor": "rac1 GTP-Binding Protein", "descriptor_ui": "D020830", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Reactive Oxygen Species", "descriptor_ui": "D017382", "major_topic": false }, { "descriptor": "TRPC Cation Channels", "descriptor_ui": "D050052", "major_topic": false }, { "descriptor": "Ventricular Dysfunction, Left", "descriptor_ui": "D018487", "major_topic": false } ], "publication": { "conference_name": null, "date": "2011 May 27", "date_precision": "day", "issue": "1", "normalized_date": "2011-05-27", "pages": "108-113", "proceedings_title": null, "publisher": "", "title": "Biochemical and biophysical research communications", "volume": "409", "year": 2011 }, "ssbd": { "database": [], "repository": [] }, "title": "TRPC3-mediated Ca2+ influx contributes to Rac1-mediated production of reactive oxygen species in MLP-deficient mouse hearts.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Vascular plants appeared ~410 million years ago then diverged into several lineages of which only two survive: the euphyllophytes (ferns and seed plants) and the lycophytes (1). We report here the genome sequence of the lycophyte Selaginella moellendorffii (Selaginella), the first non-seed vascular plant genome reported. By comparing gene content in evolutionary diverse taxa, we found that the transition from a gametophyte- to sporophyte-dominated life cycle required far fewer new genes than the transition from a non-seed vascular to a flowering plant, while secondary metabolic genes expanded extensively and in parallel in the lycophyte and angiosperm lineages. Selaginella differs in post-transcriptional gene regulation, including small RNA regulation of repetitive elements, an absence of the tasiRNA pathway and extensive RNA editing of organellar genes.", "classifications": [ { "id": "Sato", "label": "Group Sato", "parent": "Tsuchiya", "type": "group" }, { "id": "Tsuchiya", "label": "Team Tsuchiya", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Jo Ann", "last_name": "Banks", "name": null }, { "creator_type": "author", "first_name": "Tomoaki", "last_name": "Nishiyama", "name": null }, { "creator_type": "author", "first_name": "Mitsuyasu", "last_name": "Hasebe", "name": null }, { "creator_type": "author", "first_name": "John L.", "last_name": "Bowman", "name": null }, { "creator_type": "author", "first_name": "Michael", "last_name": "Gribskov", "name": null }, { "creator_type": "author", "first_name": "Claude", "last_name": "dePamphilis", "name": null }, { "creator_type": "author", "first_name": "Victor A.", "last_name": "Albert", "name": null }, { "creator_type": "author", "first_name": "Naoki", "last_name": "Aono", "name": null }, { "creator_type": "author", "first_name": "Tsuyoshi", "last_name": "Aoyama", "name": null }, { "creator_type": "author", "first_name": "Barbara A.", "last_name": "Ambrose", "name": null }, { "creator_type": "author", "first_name": "Neil W.", "last_name": "Ashton", "name": null }, { "creator_type": "author", "first_name": "Michael J.", "last_name": "Axtell", "name": null }, { "creator_type": "author", "first_name": "Elizabeth", "last_name": "Barker", "name": null }, { "creator_type": "author", "first_name": "Michael S.", "last_name": "Barker", "name": null }, { "creator_type": "author", "first_name": "Jeffrey L.", "last_name": "Bennetzen", "name": null }, { "creator_type": "author", "first_name": "Nicholas D.", "last_name": "Bonawitz", "name": null }, { "creator_type": "author", "first_name": "Clint", "last_name": "Chapple", "name": null }, { "creator_type": "author", "first_name": "Chaoyang", "last_name": "Cheng", "name": null }, { "creator_type": "author", "first_name": "Luiz Gustavo Guedes", "last_name": "Correa", "name": null }, { "creator_type": "author", "first_name": "Michael", "last_name": "Dacre", "name": null }, { "creator_type": "author", "first_name": "Jeremy", "last_name": "DeBarry", "name": null }, { "creator_type": "author", "first_name": "Ingo", "last_name": "Dreyer", "name": null }, { "creator_type": "author", "first_name": "Marek", "last_name": "Elias", "name": null }, { "creator_type": "author", "first_name": "Eric M.", "last_name": "Engstrom", "name": null }, { "creator_type": "author", "first_name": "Mark", "last_name": "Estelle", "name": null }, { "creator_type": "author", "first_name": "Liang", "last_name": "Feng", "name": null }, { "creator_type": "author", "first_name": "Cédric", "last_name": "Finet", "name": null }, { "creator_type": "author", "first_name": "Sandra K.", "last_name": "Floyd", "name": null }, { "creator_type": "author", "first_name": "Wolf B.", "last_name": "Frommer", "name": null }, { "creator_type": "author", "first_name": "Tomomichi", "last_name": "Fujita", "name": null }, { "creator_type": "author", "first_name": "Lydia", "last_name": "Gramzow", "name": null }, { "creator_type": "author", "first_name": "Michael", "last_name": "Gutensohn", "name": null }, { "creator_type": "author", "first_name": "Jesper", "last_name": "Harholt", "name": null }, { "creator_type": "author", "first_name": "Mitsuru", "last_name": "Hattori", "name": null }, { "creator_type": "author", "first_name": "Alexander", "last_name": "Heyl", "name": null }, { "creator_type": "author", "first_name": "Tadayoshi", "last_name": "Hirai", "name": null }, { "creator_type": "author", "first_name": "Yuji", "last_name": "Hiwatashi", "name": null }, { "creator_type": "author", "first_name": "Masaki", "last_name": "Ishikawa", "name": null }, { "creator_type": "author", "first_name": "Mineko", "last_name": "Iwata", "name": null }, { "creator_type": "author", "first_name": "Kenneth G.", "last_name": "Karol", "name": null }, { "creator_type": "author", "first_name": "Barbara", "last_name": "Koehler", "name": null }, { "creator_type": "author", "first_name": "Uener", "last_name": "Kolukisaoglu", "name": null }, { "creator_type": "author", "first_name": "Minoru", "last_name": "Kubo", "name": null }, { "creator_type": "author", "first_name": "Tetsuya", "last_name": "Kurata", "name": null }, { "creator_type": "author", "first_name": "Sylvie", "last_name": "Lalonde", "name": null }, { "creator_type": "author", "first_name": "Kejie", "last_name": "Li", "name": null }, { "creator_type": "author", "first_name": "Ying", "last_name": "Li", "name": null }, { "creator_type": "author", "first_name": "Amy", "last_name": "Litt", "name": null }, { "creator_type": "author", "first_name": "Eric", "last_name": "Lyons", "name": null }, { "creator_type": "author", "first_name": "Gerard", "last_name": "Manning", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Maruyama", "name": null }, { "creator_type": "author", "first_name": "Todd P.", "last_name": "Michael", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Mikami", "name": null }, { "creator_type": "author", "first_name": "Saori", "last_name": "Miyazaki", "name": null }, { "creator_type": "author", "first_name": "Shin-ichi", "last_name": "Morinaga", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Murata", "name": null }, { "creator_type": "author", "first_name": "Bernd", "last_name": "Mueller-Roeber", "name": null }, { "creator_type": "author", "first_name": "David R.", "last_name": "Nelson", "name": null }, { "creator_type": "author", "first_name": "Mari", "last_name": "Obara", "name": null }, { "creator_type": "author", "first_name": "Yasuko", "last_name": "Oguri", "name": null }, { "creator_type": "author", "first_name": "Richard G.", "last_name": "Olmstead", "name": null }, { "creator_type": "author", "first_name": "Naoko", "last_name": "Onodera", "name": null }, { "creator_type": "author", "first_name": "Bent Larsen", "last_name": "Petersen", "name": null }, { "creator_type": "author", "first_name": "Birgit", "last_name": "Pils", "name": null }, { "creator_type": "author", "first_name": "Michael", "last_name": "Prigge", "name": null }, { "creator_type": "author", "first_name": "Stefan A.", "last_name": "Rensing", "name": null }, { "creator_type": "author", "first_name": "Diego Mauricio", "last_name": "Riaño-Pachón", "name": null }, { "creator_type": "author", "first_name": "Alison W.", "last_name": "Roberts", "name": null }, { "creator_type": "author", "first_name": "Yoshikatsu", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Henrik Vibe", "last_name": "Scheller", "name": null }, { "creator_type": "author", "first_name": "Burkhard", "last_name": "Schulz", "name": null }, { "creator_type": "author", "first_name": "Christian", "last_name": "Schulz", "name": null }, { "creator_type": "author", "first_name": "Eugene V.", "last_name": "Shakirov", "name": null }, { "creator_type": "author", "first_name": "Nakako", "last_name": "Shibagaki", "name": null }, { "creator_type": "author", "first_name": "Naoki", "last_name": "Shinohara", "name": null }, { "creator_type": "author", "first_name": "Dorothy E.", "last_name": "Shippen", "name": null }, { "creator_type": "author", "first_name": "Iben", "last_name": "Sørensen", "name": null }, { "creator_type": "author", "first_name": "Ryo", "last_name": "Sotooka", "name": null }, { "creator_type": "author", "first_name": "Nagisa", "last_name": "Sugimoto", "name": null }, { "creator_type": "author", "first_name": "Mamoru", "last_name": "Sugita", "name": null }, { "creator_type": "author", "first_name": "Naomi", "last_name": "Sumikawa", "name": null }, { "creator_type": "author", "first_name": "Milos", "last_name": "Tanurdzic", "name": null }, { "creator_type": "author", "first_name": "Günter", "last_name": "Theißen", "name": null }, { "creator_type": "author", "first_name": "Peter", "last_name": "Ulvskov", "name": null }, { "creator_type": "author", "first_name": "Sachiko", "last_name": "Wakazuki", "name": null }, { "creator_type": "author", "first_name": "Jing-Ke", "last_name": "Weng", "name": null }, { "creator_type": "author", "first_name": "William W. G. T.", "last_name": "Willats", "name": null }, { "creator_type": "author", "first_name": "Daniel", "last_name": "Wipf", "name": null }, { "creator_type": "author", "first_name": "Paul G.", "last_name": "Wolf", "name": null }, { "creator_type": "author", "first_name": "Lixing", "last_name": "Yang", "name": null }, { "creator_type": "author", "first_name": "Andreas D.", "last_name": "Zimmer", "name": null }, { "creator_type": "author", "first_name": "Qihui", "last_name": "Zhu", "name": null }, { "creator_type": "author", "first_name": "Therese", "last_name": "Mitros", "name": null }, { "creator_type": "author", "first_name": "Uffe", "last_name": "Hellsten", "name": null }, { "creator_type": "author", "first_name": "Dominique", "last_name": "Loqué", "name": null }, { "creator_type": "author", "first_name": "Robert", "last_name": "Otillar", "name": null }, { "creator_type": "author", "first_name": "Asaf", "last_name": "Salamov", "name": null }, { "creator_type": "author", "first_name": "Jeremy", "last_name": "Schmutz", "name": null }, { "creator_type": "author", "first_name": "Harris", "last_name": "Shapiro", "name": null }, { "creator_type": "author", "first_name": "Erika", "last_name": "Lindquist", "name": null }, { "creator_type": "author", "first_name": "Susan", "last_name": "Lucas", "name": null }, { "creator_type": "author", "first_name": "Daniel", "last_name": "Rokhsar", "name": null }, { "creator_type": "author", "first_name": "Igor V.", "last_name": "Grigoriev", "name": null } ], "identifiers": { "doi": { "normalized": "10.1126/science.1203810" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "21551031" } }, "mesh": [ { "descriptor": "Biological Evolution", "descriptor_ui": "D005075", "major_topic": true }, { "descriptor": "Bryopsida", "descriptor_ui": "D019068", "major_topic": false }, { "descriptor": "Chlamydomonas", "descriptor_ui": "D002696", "major_topic": false }, { "descriptor": "DNA Transposable Elements", "descriptor_ui": "D004251", "major_topic": false }, { "descriptor": "Evolution, Molecular", "descriptor_ui": "D019143", "major_topic": false }, { "descriptor": "Gene Expression Regulation, Plant", "descriptor_ui": "D018506", "major_topic": false }, { "descriptor": "Genes, Plant", "descriptor_ui": "D017343", "major_topic": false }, { "descriptor": "Genome, Plant", "descriptor_ui": "D018745", "major_topic": true }, { "descriptor": "Magnoliopsida", "descriptor_ui": "D019684", "major_topic": false }, { "descriptor": "MicroRNAs", "descriptor_ui": "D035683", "major_topic": false }, { "descriptor": "Molecular Sequence Data", "descriptor_ui": "D008969", "major_topic": false }, { "descriptor": "Phylogeny", "descriptor_ui": "D010802", "major_topic": false }, { "descriptor": "Plant Proteins", "descriptor_ui": "D010940", "major_topic": false }, { "descriptor": "Proteome", "descriptor_ui": "D020543", "major_topic": false }, { "descriptor": "Repetitive Sequences, Nucleic Acid", "descriptor_ui": "D012091", "major_topic": false }, { "descriptor": "RNA Editing", "descriptor_ui": "D017393", "major_topic": false }, { "descriptor": "RNA, Plant", "descriptor_ui": "D018749", "major_topic": false }, { "descriptor": "Selaginellaceae", "descriptor_ui": "D032503", "major_topic": false }, { "descriptor": "Sequence Analysis, DNA", "descriptor_ui": "D017422", "major_topic": false } ], "publication": { "conference_name": null, "date": "2011 May 20", "date_precision": "day", "issue": "6032", "normalized_date": "2011-05-20", "pages": "960-963", "proceedings_title": null, "publisher": "", "title": "Science (New York, N.Y.)", "volume": "332", "year": 2011 }, "ssbd": { "database": [], "repository": [] }, "title": "The compact Selaginella genome identifies changes in gene content associated with the evolution of vascular plants.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The common polymorphism of p53 at codon 72, either encoding proline or arginine, has drawn attention as a genetic factor associated with clinical outcome or cancer risk for the last 2 decades. We now show that these two polymorphic variants differ in protein structure, especially within the N-terminal region and, as a consequence, differ in post-translational modification at the N terminus. The arginine form (p53-72R) shows significantly enhanced phosphorylation at Ser-6 and Ser-20 compared with the proline form (p53-72P). We also show diminished Mdm2-mediated degradation of p53-72R compared with p53-72P, which is at least partly brought about by higher levels of phosphorylation at Ser-20 in p53-72R. Furthermore, enhanced p21 expression in p53-72R-expressing cells, which is dependent on phosphorylation at Ser-6, was demonstrated. Differential p21 expression between the variants was also observed upon activation of TGF-beta signaling. Collectively, we demonstrate a novel molecular difference and simultaneously suggest a difference in the tumor-suppressing function of the variants.", "classifications": [ { "id": "Okamoto", "label": "Group Okamoto", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Chikako", "last_name": "Ozeki", "name": null }, { "creator_type": "author", "first_name": "Yuichiro", "last_name": "Sawai", "name": null }, { "creator_type": "author", "first_name": "Tatsuhiro", "last_name": "Shibata", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Kohno", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Okamoto", "name": null }, { "creator_type": "author", "first_name": "Jun", "last_name": "Yokota", "name": null }, { "creator_type": "author", "first_name": "Fumio", "last_name": "Tashiro", "name": null }, { "creator_type": "author", "first_name": "Sei-ichi", "last_name": "Tanuma", "name": null }, { "creator_type": "author", "first_name": "Ryuichi", "last_name": "Sakai", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Kawase", "name": null }, { "creator_type": "author", "first_name": "Issay", "last_name": "Kitabayashi", "name": null }, { "creator_type": "author", "first_name": "Yoichi", "last_name": "Taya", "name": null }, { "creator_type": "author", "first_name": "Rieko", "last_name": "Ohki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1074/jbc.m110.208587" }, "pmcid": { "normalized": "PMC3093897" }, "pmid": { "normalized": "21454683" } }, "mesh": [ { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "Codon", "descriptor_ui": "D003062", "major_topic": true }, { "descriptor": "Genetic Predisposition to Disease", "descriptor_ui": "D020022", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Neoplasms", "descriptor_ui": "D009369", "major_topic": true }, { "descriptor": "Phosphorylation", "descriptor_ui": "D010766", "major_topic": false }, { "descriptor": "Polymorphism, Genetic", "descriptor_ui": "D011110", "major_topic": true }, { "descriptor": "Protein Processing, Post-Translational", "descriptor_ui": "D011499", "major_topic": true }, { "descriptor": "Proto-Oncogene Proteins c-mdm2", "descriptor_ui": "D051736", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Transforming Growth Factor beta", "descriptor_ui": "D016212", "major_topic": false }, { "descriptor": "Tumor Suppressor Protein p53", "descriptor_ui": "D016159", "major_topic": true } ], "publication": { "conference_name": null, "date": "2011 May 20", "date_precision": "day", "issue": "20", "normalized_date": "2011-05-20", "pages": "18251-18260", "proceedings_title": null, "publisher": "", "title": "The Journal of biological chemistry", "volume": "286", "year": 2011 }, "ssbd": { "database": [], "repository": [] }, "title": "Cancer susceptibility polymorphism of p53 at codon 72 affects phosphorylation and degradation of p53 protein.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Although the functional significance of adult neurogenesis in hippocampal-dependent learning and memory has been well documented, the role of such neurogenesis in olfactory activity is rather obscure. To understand the significance of adult neurogenesis in olfactory functions, we genetically ablated newly born neurons by using tamoxifen-treated Nestin-CreERT2;neuron-specific enolase-diphtheria toxin fragment A (NSE-DTA) mice. In these mice, tamoxifen-inducible Cre recombinase allows the NSE (Eno2) gene to drive DTA expression in differentiating neurons, leading to the efficient ablation of newly born neurons in the forebrain. These mutant mice were capable of discriminating odors as competently as control mice. Strikingly, although control and mutant mice frequently showed freezing behaviors to a fox scent, a predator odor, mutant mice approached this odor when they were conditioned to associate the odor with a reward, whereas control mice did not approach the odor. Furthermore, although mutant males and females showed normal social recognition behaviors to other mice of a different sex, mutant males displayed deficits in male–male aggression and male sexual behaviors toward females, whereas mutant females displayed deficits in fertility and nurturing, indicating that sex-specific activities, which are known to depend on olfaction, are impaired. These results suggest that continuous neurogenesis is required for predator avoidance and sex-specific responses that are olfaction dependent and innately programmed.", "classifications": [ { "id": "Imayoshi", "label": "Group Imayoshi", "parent": "Imayoshi", "type": "group" }, { "id": "Imayoshi", "label": "Team Imayoshi", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Masayuki", "last_name": "Sakamoto", "name": null }, { "creator_type": "author", "first_name": "Itaru", "last_name": "Imayoshi", "name": null }, { "creator_type": "author", "first_name": "Toshiyuki", "last_name": "Ohtsuka", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Yamaguchi", "name": null }, { "creator_type": "author", "first_name": "Kensaku", "last_name": "Mori", "name": null }, { "creator_type": "author", "first_name": "Ryoichiro", "last_name": "Kageyama", "name": null } ], "identifiers": { "doi": { "normalized": "10.1073/pnas.1018782108" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "21536899" } }, "mesh": [ { "descriptor": "Aging", "descriptor_ui": "D000375", "major_topic": true }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Conditioning, Classical", "descriptor_ui": "D003214", "major_topic": false }, { "descriptor": "Discrimination, Psychological", "descriptor_ui": "D004192", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Freezing Reaction, Cataleptic", "descriptor_ui": "D046352", "major_topic": false }, { "descriptor": "Hippocampus", "descriptor_ui": "D006624", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Mutant Strains", "descriptor_ui": "D008817", "major_topic": false }, { "descriptor": "Neurogenesis", "descriptor_ui": "D055495", "major_topic": false }, { "descriptor": "Olfactory Perception", "descriptor_ui": "D055696", "major_topic": false }, { "descriptor": "Prosencephalon", "descriptor_ui": "D016548", "major_topic": false }, { "descriptor": "Smell", "descriptor_ui": "D012903", "major_topic": false } ], "publication": { "conference_name": null, "date": "2011 May 17", "date_precision": "day", "issue": "20", "normalized_date": "2011-05-17", "pages": "8479-8484", "proceedings_title": null, "publisher": "", "title": "Proceedings of the National Academy of Sciences of the United States of America", "volume": "108", "year": 2011 }, "ssbd": { "database": [], "repository": [] }, "title": "Continuous neurogenesis in the adult forebrain is required for innate olfactory responses.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "PURPOSE: TrkB has been involved in poor cancer outcome. TrkB mutations have been reported in non-small cell lung cancer. In this study, we aimed at characterizing the role of three potentially sensitizing TrkB mutations previously reported in lung cancer. EXPERIMENTAL DESIGN: We characterized three activation loop mutants of TrkB (M713I, R715G, and R734C) in terms of pathway activation/phosphorylation, migration, anchorage-independent growth, and sensitivity to a Trk inhibitor, using NIH3T3 cells and Baf3 cells. We also sequenced the tyrosine kinase domain of TrkB in a large number of lung cancer samples of East-Asian origin and cell lines. RESULTS: None of the mutants were constitutively active in NIH3T3 transformation and migration assays. M713I and R734C mutants showed low levels of autophosphorylation in comparison with wild-type TrkB. Although R715G showed similar level of autophosphorylation to wild-type TrkB on brain-derived neurotrophic factor stimulation, the mutant was not as competent as wild-type TrkB in supporting interleukin-3-independent growth of Baf3 cells. In addition, the Trk inhibitor AZD6918 inhibited wild-type TrkB-induced cell migration and cell growth, whereas the mutants were relatively resistant to the Trk inhibitor compared with wild-type TrkB. We could not confirm the presence of nonsynonymous mutation in 78 lung cancer samples and 29 cell lines. CONCLUSIONS: Wild-type, but not mutant, TrkB enhances cell migration and transformation. Our study suggests that TrkB mutations should not be used for selection of patients with lung cancer treated with Trk inhibitors. High expression of wild-type TrkB might be beneficial for studies of Trk inhibitors.", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Taishi", "last_name": "Harada", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null }, { "creator_type": "author", "first_name": "Masafumi", "last_name": "Takeshita", "name": null }, { "creator_type": "author", "first_name": "Takaomi", "last_name": "Koga", "name": null }, { "creator_type": "author", "first_name": "Tokujiro", "last_name": "Yano", "name": null }, { "creator_type": "author", "first_name": "Yisong", "last_name": "Wang", "name": null }, { "creator_type": "author", "first_name": "Giuseppe", "last_name": "Giaccone", "name": null } ], "identifiers": { "doi": { "normalized": "10.1158/1078-0432.ccr-10-3034" }, "pmcid": { "normalized": "PMC3086954" }, "pmid": { "normalized": "21242122" } }, "mesh": [ { "descriptor": "Amino Acid Sequence", "descriptor_ui": "D000595", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Carcinoma, Non-Small-Cell Lung", "descriptor_ui": "D002289", "major_topic": false }, { "descriptor": "Cell Movement", "descriptor_ui": "D002465", "major_topic": false }, { "descriptor": "Cell Transformation, Neoplastic", "descriptor_ui": "D002471", "major_topic": false }, { "descriptor": "DNA Mutational Analysis", "descriptor_ui": "D004252", "major_topic": false }, { "descriptor": "Gene Expression Regulation, Enzymologic", "descriptor_ui": "D015971", "major_topic": false }, { "descriptor": "Gene Expression Regulation, Neoplastic", "descriptor_ui": "D015972", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Lung Neoplasms", "descriptor_ui": "D008175", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Models, Biological", "descriptor_ui": "D008954", "major_topic": false }, { "descriptor": "Molecular Sequence Data", "descriptor_ui": "D008969", "major_topic": false }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": true }, { "descriptor": "NIH 3T3 Cells", "descriptor_ui": "D041681", "major_topic": false }, { "descriptor": "Receptor, trkB", "descriptor_ui": "D020813", "major_topic": false }, { "descriptor": "Sequence Homology, Amino Acid", "descriptor_ui": "D017386", "major_topic": false }, { "descriptor": "Tumor Cells, Cultured", "descriptor_ui": "D014407", "major_topic": false } ], "publication": { "conference_name": null, "date": "2011 May 1", "date_precision": "day", "issue": "9", "normalized_date": "2011-05-01", "pages": "2638-2645", "proceedings_title": null, "publisher": "", "title": "Clinical cancer research : an official journal of the American Association for Cancer Research", "volume": "17", "year": 2011 }, "ssbd": { "database": [], "repository": [] }, "title": "Role and relevance of TrkB mutations and expression in non-small cell lung cancer.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Cross-talk between G protein-coupled receptor (GPCR) signaling pathways serves to fine tune cellular responsiveness by neurohumoral factors. Accumulating evidence has implicated nitric oxide (NO)-based signaling downstream of GPCRs, but the molecular details are unknown. Here, we show that adenosine triphosphate (ATP) decreases angiotensin type 1 receptor (AT(1)R) density through NO-mediated S-nitrosylation of nuclear factor kappaB (NF-kappaB) in rat cardiac fibroblasts. Stimulation of purinergic P2Y(2) receptor by ATP increased expression of inducible NO synthase (iNOS) through activation of nuclear factor of activated T cells, NFATc1 and NFATc3. The ATP-induced iNOS interacted with p65 subunit of NF-kappaB in the cytosol through flavin-binding domain, which was indispensable for the locally generated NO-mediated S-nitrosylation of p65 at Cys38. beta-Arrestins anchored the formation of p65/IkappaBalpha/beta-arrestins/iNOS quaternary complex. The S-nitrosylated p65 resulted in decreases in NF-kappaB transcriptional activity and AT(1)R density. In pressure-overloaded mouse hearts, ATP released from cardiomyocytes led to decrease in AT(1)R density through iNOS-mediated S-nitrosylation of p65. These results show a unique regulatory mechanism of heterologous regulation of GPCRs in which cysteine modification of transcriptional factor rather than protein phosphorylation plays essential roles.", "classifications": [ { "id": "Nishida", "label": "Group Nishida", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Motohiro", "last_name": "Nishida", "name": null }, { "creator_type": "author", "first_name": "Mariko", "last_name": "Ogushi", "name": null }, { "creator_type": "author", "first_name": "Reiko", "last_name": "Suda", "name": null }, { "creator_type": "author", "first_name": "Miyuki", "last_name": "Toyotaka", "name": null }, { "creator_type": "author", "first_name": "Shota", "last_name": "Saiki", "name": null }, { "creator_type": "author", "first_name": "Naoyuki", "last_name": "Kitajima", "name": null }, { "creator_type": "author", "first_name": "Michio", "last_name": "Nakaya", "name": null }, { "creator_type": "author", "first_name": "Kyeong-Man", "last_name": "Kim", "name": null }, { "creator_type": "author", "first_name": "Tomomi", "last_name": "Ide", "name": null }, { "creator_type": "author", "first_name": "Yoji", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Kazuhide", "last_name": "Inoue", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Kurose", "name": null } ], "identifiers": { "doi": { "normalized": "10.1073/pnas.1017640108" }, "pmcid": { "normalized": "PMC3080971" }, "pmid": { "normalized": "21464294" } }, "mesh": [ { "descriptor": "Adenosine Triphosphate", "descriptor_ui": "D000255", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Down-Regulation", "descriptor_ui": "D015536", "major_topic": true }, { "descriptor": "Gene Expression Regulation, Enzymologic", "descriptor_ui": "D015971", "major_topic": false }, { "descriptor": "HEK293 Cells", "descriptor_ui": "D057809", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Myocardium", "descriptor_ui": "D009206", "major_topic": false }, { "descriptor": "NFATC Transcription Factors", "descriptor_ui": "D050778", "major_topic": false }, { "descriptor": "Nitric Oxide", "descriptor_ui": "D009569", "major_topic": false }, { "descriptor": "Nitric Oxide Synthase Type II", "descriptor_ui": "D052247", "major_topic": false }, { "descriptor": "Phosphorylation", "descriptor_ui": "D010766", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Receptor, Angiotensin, Type 1", "descriptor_ui": "D044140", "major_topic": false }, { "descriptor": "Receptors, Purinergic P2Y2", "descriptor_ui": "D058473", "major_topic": false }, { "descriptor": "Transcription Factor RelA", "descriptor_ui": "D051996", "major_topic": false } ], "publication": { "conference_name": null, "date": "2011 Apr 19", "date_precision": "day", "issue": "16", "normalized_date": "2011-04-19", "pages": "6662-6667", "proceedings_title": null, "publisher": "", "title": "Proceedings of the National Academy of Sciences of the United States of America", "volume": "108", "year": 2011 }, "ssbd": { "database": [], "repository": [] }, "title": "Heterologous down-regulation of angiotensin type 1 receptors by purinergic P2Y2 receptor stimulation through S-nitrosylation of NF-kappaB.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Notch-mediated lateral inhibition has been reported to regulate auditory hair cell and supporting cell development from common precursors. While the Notch effector genes Hes1, Hes5 and Hey1 are expressed in the developing cochlea, inactivation of either of them causes only mild abnormality, suggesting their functional redundancy. To explore the roles of Hes/Hey genes in cochlear development, we examined compound heterozygous or homozygous mutant mice that lacked Hes1, Hes5 and Hey1 alleles. We found that a reduction in Hes/Hey gene dosage led to graded increase of hair cell formation. However, if at least one allele of Hes1, Hes5 or Hey1 was intact, excessive hair cells were accompanied by overproduction of supporting cells, suggesting that the hair cell increase does not occur at the expense of supporting cells, and that each Hes/Hey gene functions to induce supporting cells. By contrast, when all alleles of Hes1, Hes5 and Hey1 were inactivated, the number of hair cells increased more drastically, whereas that of supporting cells was unchanged compared with control, suggesting that supporting cell formation was balanced by their overproduction and fate conversion into hair cells. The increase of the cell numbers seemed to occur after the prosensory domain formation in the mutants because the proliferation state and the size of the prosensory domain were not affected. Thus, Hes1, Hes5 and Hey1 cooperatively inhibit hair cell formation, and one allele of Hes1, Hes5 or Hey1 is sufficient for supporting cell production probably by lateral inhibition in the sensory epithelium. Strikingly, Hes/Hey mutations lead to disorganized cell alignment and polarity and to hearing loss despite hair cell overproduction. These results suggest that Hes/Hey gene dosage is essential not only for generation of appropriate numbers of hair cells and supporting cells by controlling cell proliferation and lateral inhibition but also for the hearing ability by regulating the cell alignment and polarity.", "classifications": [ { "id": "Imayoshi", "label": "Group Imayoshi", "parent": "Imayoshi", "type": "group" }, { "id": "Imayoshi", "label": "Team Imayoshi", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Tomoko", "last_name": "Tateya", "name": null }, { "creator_type": "author", "first_name": "Itaru", "last_name": "Imayoshi", "name": null }, { "creator_type": "author", "first_name": "Ichiro", "last_name": "Tateya", "name": null }, { "creator_type": "author", "first_name": "Juichi", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Ryoichiro", "last_name": "Kageyama", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.ydbio.2011.01.038" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "21300049" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Basic Helix-Loop-Helix Proteins", "descriptor_ui": "D051792", "major_topic": false }, { "descriptor": "Cell Cycle Proteins", "descriptor_ui": "D018797", "major_topic": false }, { "descriptor": "Cell Polarity", "descriptor_ui": "D016764", "major_topic": false }, { "descriptor": "Cell Proliferation", "descriptor_ui": "D049109", "major_topic": false }, { "descriptor": "Cochlea", "descriptor_ui": "D003051", "major_topic": false }, { "descriptor": "Gene Dosage", "descriptor_ui": "D018628", "major_topic": false }, { "descriptor": "Gene Expression Regulation, Developmental", "descriptor_ui": "D018507", "major_topic": false }, { "descriptor": "Hair Cells, Auditory", "descriptor_ui": "D006198", "major_topic": false }, { "descriptor": "Hearing Loss", "descriptor_ui": "D034381", "major_topic": false }, { "descriptor": "Heterozygote", "descriptor_ui": "D006579", "major_topic": false }, { "descriptor": "Homeodomain Proteins", "descriptor_ui": "D018398", "major_topic": false }, { "descriptor": "Homozygote", "descriptor_ui": "D006720", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Inbred ICR", "descriptor_ui": "D008813", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Mice, Transgenic", "descriptor_ui": "D008822", "major_topic": false }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": false }, { "descriptor": "Phenotype", "descriptor_ui": "D010641", "major_topic": false }, { "descriptor": "Receptors, Notch", "descriptor_ui": "D051880", "major_topic": false }, { "descriptor": "Repressor Proteins", "descriptor_ui": "D012097", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Transcription Factor HES-1", "descriptor_ui": "D000072056", "major_topic": false } ], "publication": { "conference_name": null, "date": "2011 Apr 15", "date_precision": "day", "issue": "2", "normalized_date": "2011-04-15", "pages": "329-340", "proceedings_title": null, "publisher": "", "title": "Developmental biology", "volume": "352", "year": 2011 }, "ssbd": { "database": [], "repository": [] }, "title": "Cooperative functions of Hes/Hey genes in auditory hair cell and supporting cell development.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "In mammals, cellular circadian rhythms are generated by a transcriptional-translational autoregulatory network that consists of clock genes that encode transcriptional regulators. Of these clock genes, Period1 (Per1) and Period2 (Per2) are essential for sustainable circadian rhythmicity and photic entrainment. Intriguingly, Per1 and Per2 mRNAs exhibit circadian oscillations with a 4-hour phase difference, but they are similarly transactivated by CLOCK-BMAL1. In this study, we investigated the mechanism underlying the phase difference between Per1 and Per2 through a combination of mathematical simulations and molecular experiments. Mathematical analyses of a model for the mammalian circadian oscillator demonstrated that the slow synthesis and fast degradation of mRNA tend to advance the oscillation phase of mRNA expression. However, the phase difference between Per1 and Per2 was not reproduced by the model, which implemented a 1.1-fold difference in degradation rates and a 3-fold difference in CLOCK-BMAL1 mediated inductions of Per1 and Per2 as estimated in cultured mammalian cells. Thus, we hypothesized the existence of a novel transcriptional activation of Per2 by PER1/2 such that the Per2 oscillation phase was delayed. Indeed, only the Per2 promoter, but not Per1, was strongly induced by both PER1 and PER2 in the presence of CLOCK-BMAL1 in a luciferase reporter assay. Moreover, a 3-hour advance was observed in the transcriptional oscillation of the delta-Per2 reporter gene lacking cis-elements required for the induction by PER1/2. These results indicate that the Per2 positive feedback regulation is a significant factor responsible for generating the phase difference between Per1 and Per2 gene expression.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yukino", "last_name": "Ogawa", "name": null }, { "creator_type": "author", "first_name": "Nobuya", "last_name": "Koike", "name": null }, { "creator_type": "author", "first_name": "Gen", "last_name": "Kurosawa", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Masaru", "last_name": "Tomita", "name": null }, { "creator_type": "author", "first_name": "Hajime", "last_name": "Tei", "name": null } ], "identifiers": { "doi": { "normalized": "10.1371/journal.pone.0018663" }, "pmcid": { "normalized": "PMC3077398" }, "pmid": { "normalized": "21533189" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Gene Expression Regulation", "descriptor_ui": "D005786", "major_topic": true }, { "descriptor": "Mammals", "descriptor_ui": "D008322", "major_topic": false }, { "descriptor": "Period Circadian Proteins", "descriptor_ui": "D056950", "major_topic": false }, { "descriptor": "RNA, Messenger", "descriptor_ui": "D012333", "major_topic": false } ], "publication": { "conference_name": null, "date": "2011 Apr 14", "date_precision": "day", "issue": "4", "normalized_date": "2011-04-14", "pages": "e18663", "proceedings_title": null, "publisher": "", "title": "PloS one", "volume": "6", "year": 2011 }, "ssbd": { "database": [], "repository": [] }, "title": "Positive autoregulation delays the expression phase of mammalian clock gene Per2.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Balanced organogenesis requires the orchestration of multiple cellular interactions to create the collective cell behaviours that progressively shape developing tissues. It is currently unclear how individual, localized parts are able to coordinate with each other to develop a whole organ shape. Here we report the dynamic, autonomous formation of the optic cup (retinal primordium) structure from a three-dimensional culture of mouse embryonic stem cell aggregates. Embryonic-stem-cell-derived retinal epithelium spontaneously formed hemispherical epithelial vesicles that became patterned along their proximal-distal axis. Whereas the proximal portion differentiated into mechanically rigid pigment epithelium, the flexible distal portion progressively folded inward to form a shape reminiscent of the embryonic optic cup, exhibited interkinetic nuclear migration and generated stratified neural retinal tissue, as seen in vivo. We demonstrate that optic-cup morphogenesis in this simple cell culture depends on an intrinsic self-organizing program involving stepwise and domain-specific regulation of local epithelial properties.", "classifications": [ { "id": "Okuda", "label": "Group Okuda", "parent": "Imayoshi", "type": "group" }, { "id": "Imayoshi", "label": "Team Imayoshi", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Mototsugu", "last_name": "Eiraku", "name": null }, { "creator_type": "author", "first_name": "Nozomu", "last_name": "Takata", "name": null }, { "creator_type": "author", "first_name": "Hiroki", "last_name": "Ishibashi", "name": null }, { "creator_type": "author", "first_name": "Masako", "last_name": "Kawada", "name": null }, { "creator_type": "author", "first_name": "Eriko", "last_name": "Sakakura", "name": null }, { "creator_type": "author", "first_name": "Satoru", "last_name": "Okuda", "name": null }, { "creator_type": "author", "first_name": "Kiyotoshi", "last_name": "Sekiguchi", "name": null }, { "creator_type": "author", "first_name": "Taiji", "last_name": "Adachi", "name": null }, { "creator_type": "author", "first_name": "Yoshiki", "last_name": "Sasai", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/nature09941" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "21475194" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Culture Techniques", "descriptor_ui": "D018929", "major_topic": false }, { "descriptor": "Embryonic Stem Cells", "descriptor_ui": "D053595", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Morphogenesis", "descriptor_ui": "D009024", "major_topic": true }, { "descriptor": "Neural Plate", "descriptor_ui": "D054258", "major_topic": false }, { "descriptor": "Neural Stem Cells", "descriptor_ui": "D058953", "major_topic": false }, { "descriptor": "Organ Culture Techniques", "descriptor_ui": "D009924", "major_topic": false }, { "descriptor": "Organogenesis", "descriptor_ui": "D038081", "major_topic": true }, { "descriptor": "Regenerative Medicine", "descriptor_ui": "D044968", "major_topic": false }, { "descriptor": "Retina", "descriptor_ui": "D012160", "major_topic": false }, { "descriptor": "Retinal Pigment Epithelium", "descriptor_ui": "D055213", "major_topic": false } ], "publication": { "conference_name": null, "date": "2011 Apr 7", "date_precision": "day", "issue": "7341", "normalized_date": "2011-04-07", "pages": "51-56", "proceedings_title": null, "publisher": "", "title": "Nature", "volume": "472", "year": 2011 }, "ssbd": { "database": [], "repository": [] }, "title": "Self-organizing optic-cup morphogenesis in three-dimensional culture.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "", "classifications": [ { "id": "Sodeoka", "label": "Group Sodeoka", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Go", "last_name": "Hirai", "name": null }, { "creator_type": "author", "first_name": "Ayako", "last_name": "Tsuchiya", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Koyama", "name": null }, { "creator_type": "author", "first_name": "Yuko", "last_name": "Otani", "name": null }, { "creator_type": "author", "first_name": "Kana", "last_name": "Oonuma", "name": null }, { "creator_type": "author", "first_name": "Kosuke", "last_name": "Dodo", "name": null }, { "creator_type": "author", "first_name": "Siro", "last_name": "Simizu", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Osada", "name": null }, { "creator_type": "author", "first_name": "Mikiko", "last_name": "Sodeoka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/cmdc.201100107" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "21391303" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Biological Products", "descriptor_ui": "D001688", "major_topic": false }, { "descriptor": "Cell Cycle", "descriptor_ui": "D002453", "major_topic": false }, { "descriptor": "Dual-Specificity Phosphatases", "descriptor_ui": "D054637", "major_topic": false }, { "descriptor": "Enzyme Inhibitors", "descriptor_ui": "D004791", "major_topic": false }, { "descriptor": "Inhibitory Concentration 50", "descriptor_ui": "D020128", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Molecular Mimicry", "descriptor_ui": "D018716", "major_topic": false }, { "descriptor": "NIH 3T3 Cells", "descriptor_ui": "D041681", "major_topic": false }, { "descriptor": "Phosphates", "descriptor_ui": "D010710", "major_topic": false }, { "descriptor": "Structure-Activity Relationship", "descriptor_ui": "D013329", "major_topic": false }, { "descriptor": "Tumor Cells, Cultured", "descriptor_ui": "D014407", "major_topic": false }, { "descriptor": "Vaccinia virus", "descriptor_ui": "D014616", "major_topic": false } ], "publication": { "conference_name": null, "date": "2011 Apr 4", "date_precision": "day", "issue": "4", "normalized_date": "2011-04-04", "pages": "617-622", "proceedings_title": null, "publisher": "", "title": "ChemMedChem", "volume": "6", "year": 2011 }, "ssbd": { "database": [], "repository": [] }, "title": "Development of a Vaccinia H1-related (VHR) phosphatase inhibitor with a nonacidic phosphate-mimicking core structure.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "An aziridine moiety on the fullerene core can serve as an acid-triggered reacting template for the controlled synthesis of a range of functionalized fullerenes that are otherwise difficult to synthesize in an efficient and selective manner. A copper-catalyzed aziridination of C(60) for the practical synthesis of aziridinofullerene 1 and acid-catalyzed reactions of 1 with mono- and bifunctional nucleophiles as well as alkynes are described. The rapid generation of structural diversity in a single chemical operation using the common platform 1 is notable.", "classifications": [ { "id": "Nanbo", "label": "Group Nanbo", "parent": "Tsuchiya", "type": "group" }, { "id": "Tsuchiya", "label": "Team Tsuchiya", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Masakazu", "last_name": "Nambo", "name": null }, { "creator_type": "author", "first_name": "Yasutomo", "last_name": "Segawa", "name": null }, { "creator_type": "author", "first_name": "Kenichiro", "last_name": "Itami", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/ja111213k" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "21302952" } }, "mesh": [ { "descriptor": "Aziridines", "descriptor_ui": "D001388", "major_topic": false }, { "descriptor": "Fullerenes", "descriptor_ui": "D037741", "major_topic": false }, { "descriptor": "Ligands", "descriptor_ui": "D008024", "major_topic": false }, { "descriptor": "Molecular Structure", "descriptor_ui": "D015394", "major_topic": false } ], "publication": { "conference_name": null, "date": "2011 Mar 2", "date_precision": "day", "issue": "8", "normalized_date": "2011-03-02", "pages": "2402-2405", "proceedings_title": null, "publisher": "", "title": "Journal of the American Chemical Society", "volume": "133", "year": 2011 }, "ssbd": { "database": [], "repository": [] }, "title": "Aziridinofullerene: a versatile platform for functionalized fullerenes.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "In skeletal muscle differentiation, muscle-specific genes are regulated by two groups of transcription factors, the MyoD and MEF2 families, which work together to drive the differentiation process. Here, we show that ERK5 regulates muscle cell fusion through Klf transcription factors. The inhibition of ERK5 activity suppresses muscle cell fusion with minimal effects on the expression of MyoD, MEF2, and their target genes. Promoter analysis coupled to microarray assay reveals that Klf-binding motifs are highly enriched in the promoter regions of ERK5-dependent upregulated genes. Remarkably, Klf2 and Klf4 expression are also upregulated during differentiation in an ERK5-dependent manner, and knockdown of Klf2 or Klf4 specifically suppresses muscle cell fusion. Moreover, we show that Sp1 transcription factor links ERK5 to Klf2/4, and that nephronectin, a Klf transcriptional target, is involved in muscle cell fusion. Therefore, an ERK5/Sp1/Klf module plays a key role in the fusion process during skeletal muscle differentiation.", "classifications": [ { "id": "Yamamoto", "label": "Group Yamamoto", "parent": "Toyoshima", "type": "group" }, { "id": "Toyoshima", "label": "Team Toyoshima", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Kazunori", "last_name": "Sunadome", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Miki", "last_name": "Ebisuya", "name": null }, { "creator_type": "author", "first_name": "Kunio", "last_name": "Kondoh", "name": null }, { "creator_type": "author", "first_name": "Atsuko", "last_name": "Sehara-Fujisawa", "name": null }, { "creator_type": "author", "first_name": "Eisuke", "last_name": "Nishida", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.devcel.2010.12.005" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "21316587" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Base Sequence", "descriptor_ui": "D001483", "major_topic": false }, { "descriptor": "Bone Morphogenetic Protein 2", "descriptor_ui": "D055396", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Cell Fusion", "descriptor_ui": "D002459", "major_topic": false }, { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "Extracellular Matrix Proteins", "descriptor_ui": "D016326", "major_topic": false }, { "descriptor": "Fibroblast Growth Factor 2", "descriptor_ui": "D016222", "major_topic": false }, { "descriptor": "Gene Expression Profiling", "descriptor_ui": "D020869", "major_topic": false }, { "descriptor": "Insulin-Like Growth Factor I", "descriptor_ui": "D007334", "major_topic": false }, { "descriptor": "Kruppel-Like Factor 4", "descriptor_ui": "D000090062", "major_topic": false }, { "descriptor": "Kruppel-Like Transcription Factors", "descriptor_ui": "D051741", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mitogen-Activated Protein Kinase 7", "descriptor_ui": "D048054", "major_topic": false }, { "descriptor": "Molecular Sequence Data", "descriptor_ui": "D008969", "major_topic": false }, { "descriptor": "Muscle Cells", "descriptor_ui": "D032342", "major_topic": false }, { "descriptor": "Muscle Development", "descriptor_ui": "D024510", "major_topic": false }, { "descriptor": "MyoD Protein", "descriptor_ui": "D017570", "major_topic": false }, { "descriptor": "Promoter Regions, Genetic", "descriptor_ui": "D011401", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Sp1 Transcription Factor", "descriptor_ui": "D016329", "major_topic": false }, { "descriptor": "Transcription, Genetic", "descriptor_ui": "D014158", "major_topic": false }, { "descriptor": "Up-Regulation", "descriptor_ui": "D015854", "major_topic": false } ], "publication": { "conference_name": null, "date": "2011 Feb 15", "date_precision": "day", "issue": "2", "normalized_date": "2011-02-15", "pages": "192-205", "proceedings_title": null, "publisher": "", "title": "Developmental cell", "volume": "20", "year": 2011 }, "ssbd": { "database": [], "repository": [] }, "title": "ERK5 regulates muscle cell fusion through Klf transcription factors.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "During early telencephalic development, the major portion of the ventral telencephalic (subpallial) region becomes subdivided into three regions, the lateral (LGE), medial (MGE), and caudal (CGE) ganglionic eminences. In this study, we systematically recapitulated subpallial patterning in mouse embryonic stem cell (ESC) cultures and investigated temporal and combinatory actions of patterning signals. In serum-free floating culture, the dorsal-ventral specification of ESC-derived telencephalic neuroectoderm is dose-dependently directed by Sonic hedgehog (Shh) signaling. Early Shh treatment, even before the expression onset of Foxg1 (also Bf1; earliest marker of the telencephalic lineage), is critical for efficiently generating LGE progenitors, and continuous Shh signaling until day 9 is necessary to commit these cells to the LGE lineage. When induced under these conditions and purified by fluorescence-activated cell sorter, telencephalic cells efficiently differentiated into Nolz1+/Ctip2+ LGE neuronal precursors and subsequently, both in culture and after in vivo grafting, into DARPP32+ medium-sized spiny neurons. Purified telencephalic progenitors treated with high doses of the Hedgehog (Hh) agonist SAG (Smoothened agonist) differentiated into MGE- and CGE-like tissues. Interestingly, in addition to strong Hh signaling, the efficient specification of MGE cells requires Fgf8 signaling but is inhibited by treatment with Fgf15/19. In contrast, CGE differentiation is promoted by Fgf15/19 but suppressed by Fgf8, suggesting that specific Fgf signals play different, critical roles in the positional specification of ESC-derived ventral subpallial tissues. We discuss a model of the antagonistic Fgf8 and Fgf15/19 signaling in rostral-caudal subpallial patterning and compare it with the roles of these molecules in cortical patterning.", "classifications": [ { "id": "Eiraku", "label": "Group Eiraku", "parent": "Eiraku", "type": "group" }, { "id": "Eiraku", "label": "Team Eiraku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Teruko", "last_name": "Danjo", "name": null }, { "creator_type": "author", "first_name": "Mototsugu", "last_name": "Eiraku", "name": null }, { "creator_type": "author", "first_name": "Keiko", "last_name": "Muguruma", "name": null }, { "creator_type": "author", "first_name": "Kiichi", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Masako", "last_name": "Kawada", "name": null }, { "creator_type": "author", "first_name": "Yuchio", "last_name": "Yanagawa", "name": null }, { "creator_type": "author", "first_name": "John L. R.", "last_name": "Rubenstein", "name": null }, { "creator_type": "author", "first_name": "Yoshiki", "last_name": "Sasai", "name": null } ], "identifiers": { "doi": { "normalized": "10.1523/jneurosci.5128-10.2011" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "21289201" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Carrier Proteins", "descriptor_ui": "D002352", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Cyclohexylamines", "descriptor_ui": "D003514", "major_topic": false }, { "descriptor": "Embryonic Stem Cells", "descriptor_ui": "D053595", "major_topic": false }, { "descriptor": "Fibroblast Growth Factor 8", "descriptor_ui": "D051524", "major_topic": false }, { "descriptor": "Fibroblast Growth Factors", "descriptor_ui": "D005346", "major_topic": false }, { "descriptor": "Flow Cytometry", "descriptor_ui": "D005434", "major_topic": false }, { "descriptor": "Forkhead Transcription Factors", "descriptor_ui": "D051858", "major_topic": false }, { "descriptor": "Hedgehog Proteins", "descriptor_ui": "D053823", "major_topic": false }, { "descriptor": "Immunohistochemistry", "descriptor_ui": "D007150", "major_topic": false }, { "descriptor": "Intracellular Signaling Peptides and Proteins", "descriptor_ui": "D047908", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Nerve Tissue Proteins", "descriptor_ui": "D009419", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Nuclear Proteins", "descriptor_ui": "D009687", "major_topic": false }, { "descriptor": "Polymerase Chain Reaction", "descriptor_ui": "D016133", "major_topic": false }, { "descriptor": "Repressor Proteins", "descriptor_ui": "D012097", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Telencephalon", "descriptor_ui": "D013687", "major_topic": false }, { "descriptor": "Thiophenes", "descriptor_ui": "D013876", "major_topic": false }, { "descriptor": "Time Factors", "descriptor_ui": "D013997", "major_topic": false }, { "descriptor": "Tumor Suppressor Proteins", "descriptor_ui": "D025521", "major_topic": false } ], "publication": { "conference_name": null, "date": "2011 Feb 2", "date_precision": "day", "issue": "5", "normalized_date": "2011-02-02", "pages": "1919-1933", "proceedings_title": null, "publisher": "", "title": "The Journal of Neuroscience", "volume": "31", "year": 2011 }, "ssbd": { "database": [], "repository": [] }, "title": "Subregional Specification of Embryonic Stem Cell-Derived Ventral Telencephalic Tissues by Timed and Combinatory Treatment with Extrinsic Signals.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "A Rh-catalyzed reaction of C(60) and C(70) with organoboron compounds is described. This new catalytic method enables introduction of various organic groups onto C(60) and C(70). [Rh(cod)(MeCN)(2)]BF(4) proved to be the most effective catalyst in terms of productivity and selectivity. The reaction generally proceeds with a high regioselectivity and in a mono-addition selective manner. It was found that water is an essential additive to promote the reaction. By X-ray crystal structure analysis, we have confirmed the reaction site of organometallic-based hydroarylation of C(70) for the first time. Various functional fullerenes, such as fullerene-tagged amino acids and fullerene-capped pi systems, can be synthesized. The X-ray crystal structure of biphenyl-attached C(60) revealed an interesting opportunity for the well-organized alignment of bucky balls by taking advantage of CH-pi interactions.", "classifications": [ { "id": "Nanbo", "label": "Group Nanbo", "parent": "Tsuchiya", "type": "group" }, { "id": "Tsuchiya", "label": "Team Tsuchiya", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Masakazu", "last_name": "Nambo", "name": null }, { "creator_type": "author", "first_name": "Yasutomo", "last_name": "Segawa", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Wakamiya", "name": null }, { "creator_type": "author", "first_name": "Kenichiro", "last_name": "Itami", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/asia.201000583" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "20963810" } }, "mesh": [], "publication": { "conference_name": null, "date": "2011 Feb 1", "date_precision": "day", "issue": "2", "normalized_date": "2011-02-01", "pages": "590-598", "proceedings_title": null, "publisher": "", "title": "Chemistry, an Asian journal", "volume": "6", "year": 2011 }, "ssbd": { "database": [], "repository": [] }, "title": "Selective introduction of organic groups to C60 and C70 using organoboron compounds and rhodium catalyst: a new synthetic approach to organo(hydro)fullerenes.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The tandem aza-Michael reaction/enantioselective protonation of alpha-substituted alpha,beta-unsaturated carbonyl compounds is described in detail. The key to success is the combined use of a Bronsted basic palladium-mu-hydroxo complex and amine salts, which allows for the controlled generation of active catalyst and nucleophilic free amines. This catalytic system was applicable to various acceptors and aromatic amines, and the desired beta-amino acid derivatives with a chiral center at the alpha position were produced in good yield with excellent enantioselectivity (up to 98% ee). For electron-deficient amines, the introduction of free amine as an additive was effective in promoting the reaction. The results of mechanistic studies, including determination of the absolute configuration of the product, are discussed.", "classifications": [ { "id": "Sodeoka", "label": "Group Sodeoka", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yoshitaka", "last_name": "Hamashima", "name": null }, { "creator_type": "author", "first_name": "Shoko", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Toshihiro", "last_name": "Tamura", "name": null }, { "creator_type": "author", "first_name": "Hidenori", "last_name": "Somei", "name": null }, { "creator_type": "author", "first_name": "Mikiko", "last_name": "Sodeoka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/asia.201000740" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "21254440" } }, "mesh": [ { "descriptor": "Amines", "descriptor_ui": "D000588", "major_topic": false }, { "descriptor": "Amino Acids", "descriptor_ui": "D000596", "major_topic": false }, { "descriptor": "Hydrogenation", "descriptor_ui": "D006865", "major_topic": false }, { "descriptor": "Palladium", "descriptor_ui": "D010165", "major_topic": false }, { "descriptor": "Protons", "descriptor_ui": "D011522", "major_topic": false }, { "descriptor": "Salts", "descriptor_ui": "D012492", "major_topic": false }, { "descriptor": "Stereoisomerism", "descriptor_ui": "D013237", "major_topic": false } ], "publication": { "conference_name": null, "date": "2011 Feb 1", "date_precision": "day", "issue": "2", "normalized_date": "2011-02-01", "pages": "658-668", "proceedings_title": null, "publisher": "", "title": "Chemistry, an Asian journal", "volume": "6", "year": 2011 }, "ssbd": { "database": [], "repository": [] }, "title": "Scope and mechanism of tandem aza-Michael reaction/enantioselective protonation using a Pd-mu-hydroxo complex under mild conditions buffered with amine salts.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The development of direction selectivity in the visual system depends on visual experience. In the developing Xenopus retinotectal system, tectal neurons (TNs) become direction selective through spike timing-dependent plasticity (STDP) after repetitive retinal exposure to a moving bar in a specific direction. We investigated the mechanism responsible for the development of direction selectivity in the Xenopus retinotectal system using a neural circuit model with STDP. In this retinotectal circuit model, a moving bar stimulated the retinal ganglion cells (RGCs), which provided feedforward excitation to the TNs and interneurons (INs). The INs provided delayed feedforward inhibition to the TNs. The TNs also received feedback excitation from neighboring TNs. As a synaptic learning rule, a molecular STDP model was used for synapses between the RGCs and TNs. The retinotectal circuit model reproduced experimentally observed features of the development of direction selectivity, such as increase in input to the TN. The peak of feedforward excitation from RGCs to TNs shifted earlier as a result of STDP. Together with the delayed feedforward inhibition, a stronger earlier transient feedforward signal was generated, which exceeded the threshold of the feedback excitation from the neighboring TNs and resulted in amplification of input to the TN. The suppression of the delayed feedforward inhibition resulted in the development of orientation selectivity rather than direction selectivity, indicating the pivotal role of the delayed feedforward inhibition in direction selectivity. We propose a mechanism for the development of direction selectivity involving a delayed feedforward inhibition with STDP and the amplification of feedback excitation.", "classifications": [ { "id": "Kuroda", "label": "Group Kuroda", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Minoru", "last_name": "Honda", "name": null }, { "creator_type": "author", "first_name": "Hidetoshi", "last_name": "Urakubo", "name": null }, { "creator_type": "author", "first_name": "Keiko", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Kuroda", "name": null } ], "identifiers": { "doi": { "normalized": "10.1523/jneurosci.3811-10.2011" }, "pmcid": { "normalized": "PMC6623591" }, "pmid": { "normalized": "21273436" } }, "mesh": [ { "descriptor": "Action Potentials", "descriptor_ui": "D000200", "major_topic": true }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Feedback, Physiological", "descriptor_ui": "D025461", "major_topic": false }, { "descriptor": "Interneurons", "descriptor_ui": "D007395", "major_topic": false }, { "descriptor": "Larva", "descriptor_ui": "D007814", "major_topic": false }, { "descriptor": "Models, Neurological", "descriptor_ui": "D008959", "major_topic": true }, { "descriptor": "Motion Perception", "descriptor_ui": "D009039", "major_topic": true }, { "descriptor": "Neuronal Plasticity", "descriptor_ui": "D009473", "major_topic": true }, { "descriptor": "Photic Stimulation", "descriptor_ui": "D010775", "major_topic": false }, { "descriptor": "Retina", "descriptor_ui": "D012160", "major_topic": false }, { "descriptor": "Retinal Ganglion Cells", "descriptor_ui": "D012165", "major_topic": false }, { "descriptor": "Superior Colliculi", "descriptor_ui": "D013477", "major_topic": false }, { "descriptor": "Synapses", "descriptor_ui": "D013569", "major_topic": false }, { "descriptor": "Xenopus", "descriptor_ui": "D014981", "major_topic": false } ], "publication": { "conference_name": null, "date": "2011 Jan 26", "date_precision": "day", "issue": "4", "normalized_date": "2011-01-26", "pages": "1516-1527", "proceedings_title": null, "publisher": "", "title": "The Journal of neuroscience : the official journal of the Society for Neuroscience", "volume": "31", "year": 2011 }, "ssbd": { "database": [], "repository": [] }, "title": "Analysis of development of direction selectivity in retinotectum by a neural circuit model with spike timing-dependent plasticity.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "DNA transposons have been widely used for transgenesis and insertional mutagenesis in various organisms. Among the transposons active in mammalian cells, the moth-derived transposon piggyBac is most promising with its highly efficient transposition, large cargo capacity, and precise repair of the donor site. Here we report the generation of a hyperactive piggyBac transposase. The active transposition of piggyBac in multiple organisms allowed us to screen a transposase mutant library in yeast for hyperactive mutants and then to test candidates in mouse ES cells. We isolated 18 hyperactive mutants in yeast, among which five were also hyperactive in mammalian cells. By combining all mutations, a total of 7 aa substitutions, into a single reading frame, we generated a unique hyperactive piggyBac transposase with 17-fold and ninefold increases in excision and integration, respectively. We showed its applicability by demonstrating an increased efficiency of generation of transgene-free mouse induced pluripotent stem cells. We also analyzed whether this hyperactive piggyBac transposase affects the genomic integrity of the host cells. The frequency of footprints left by the hyperactive piggyBac transposase was as low as WT transposase (~1%) and we found no evidence that the expression of the transposase affects genomic integrity. This hyperactive piggyBac transposase expands the utility of the piggyBac transposon for applications in mammalian genetics and gene therapy.", "classifications": [ { "id": "Yusa", "label": "Group Yusa", "parent": "Eiraku", "type": "group" }, { "id": "Eiraku", "label": "Team Eiraku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Kosuke", "last_name": "Yusa", "name": null }, { "creator_type": "author", "first_name": "Liqin", "last_name": "Zhou", "name": null }, { "creator_type": "author", "first_name": "Meng Amy", "last_name": "Li", "name": null }, { "creator_type": "author", "first_name": "Allan", "last_name": "Bradley", "name": null }, { "creator_type": "author", "first_name": "Nancy L.", "last_name": "Craig", "name": null } ], "identifiers": { "doi": { "normalized": "10.1073/pnas.1008322108" }, "pmcid": { "normalized": "PMC3029773" }, "pmid": { "normalized": "21205896" } }, "mesh": [ { "descriptor": "Alternative Splicing", "descriptor_ui": "D017398", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Comparative Genomic Hybridization", "descriptor_ui": "D055028", "major_topic": false }, { "descriptor": "DNA Transposable Elements", "descriptor_ui": "D004251", "major_topic": false }, { "descriptor": "Embryo, Mammalian", "descriptor_ui": "D004622", "major_topic": false }, { "descriptor": "Embryonic Stem Cells", "descriptor_ui": "D053595", "major_topic": false }, { "descriptor": "Fibroblasts", "descriptor_ui": "D005347", "major_topic": false }, { "descriptor": "Genome", "descriptor_ui": "D016678", "major_topic": false }, { "descriptor": "HEK293 Cells", "descriptor_ui": "D057809", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Induced Pluripotent Stem Cells", "descriptor_ui": "D057026", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Models, Genetic", "descriptor_ui": "D008957", "major_topic": false }, { "descriptor": "Moths", "descriptor_ui": "D009036", "major_topic": false }, { "descriptor": "Mutagenesis, Insertional", "descriptor_ui": "D016254", "major_topic": true }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": false }, { "descriptor": "Saccharomyces cerevisiae", "descriptor_ui": "D012441", "major_topic": false }, { "descriptor": "Saccharomyces cerevisiae Proteins", "descriptor_ui": "D029701", "major_topic": false }, { "descriptor": "Transposases", "descriptor_ui": "D019895", "major_topic": false } ], "publication": { "conference_name": null, "date": "2011 Jan 25", "date_precision": "day", "issue": "4", "normalized_date": "2011-01-25", "pages": "1531-1536", "proceedings_title": null, "publisher": "", "title": "Proceedings of the National Academy of Sciences of the United States of America", "volume": "108", "year": 2011 }, "ssbd": { "database": [], "repository": [] }, "title": "A hyperactive piggyBac transposase for mammalian applications.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "A balance between cell survival and apoptosis is essential for animal development. Although proper development involves multiple interactions between germ layers, little is known about the intercellular and intertissue signaling pathways that promote cell survival in neighboring or distant germ layers. We found that serum- and glucocorticoid-inducible kinase 1 (SGK1) promoted ectodermal cell survival during early Xenopus embryogenesis through a non-cell-autonomous mechanism. Dorsal depletion of SGK1 in Xenopus embryos resulted in shortened axes and reduced head structures with defective eyes, and ventral depletion led to defective tail morphologies. Although the gene encoding SGK1 was mainly expressed in the endoderm and dorsal mesoderm, knockdown of SGK1 caused excessive apoptosis in the ectoderm. SGK1-depleted ectodermal explants showed little or no apoptosis, suggesting non-cell-autonomous effects of SGK1 on ectodermal cells. Microarray analysis revealed that SGK1 knockdown increased the expression of genes encoding FADD (Fas-associated death domain protein) and caspase-10, components of the death-inducing signaling complex (DISC). Inhibition of DISC function suppressed excessive apoptosis in SGK1-knockdown embryos. SGK1 acted through the transcription factor nuclear factor kappaB (NF-kappaB) to stimulate production of bone morphogenetic protein 7 (BMP7), and overexpression of BMP7 in SGK1-knockdown embryos reduced the abundance of DISC components. We show that phosphoinositide 3-kinase (PI3K) functioned upstream of SGK1, thus revealing an endodermal and mesodermal pathway from PI3K to SGK1 to NF-kappaB that produces BMP7, which promotes ectodermal survival by decreasing DISC function.", "classifications": [ { "id": "Yamamoto", "label": "Group Yamamoto", "parent": "Toyoshima", "type": "group" }, { "id": "Toyoshima", "label": "Team Toyoshima", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Endo", "name": null }, { "creator_type": "author", "first_name": "Morioh", "last_name": "Kusakabe", "name": null }, { "creator_type": "author", "first_name": "Kazunori", "last_name": "Sunadome", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Eisuke", "last_name": "Nishida", "name": null } ], "identifiers": { "doi": { "normalized": "10.1126/scisignal.2001211" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "21245468" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Apoptosis", "descriptor_ui": "D017209", "major_topic": false }, { "descriptor": "Body Patterning", "descriptor_ui": "D019521", "major_topic": false }, { "descriptor": "Bone Morphogenetic Protein 7", "descriptor_ui": "D055419", "major_topic": false }, { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "Chromatin Immunoprecipitation", "descriptor_ui": "D047369", "major_topic": false }, { "descriptor": "Ectoderm", "descriptor_ui": "D004475", "major_topic": false }, { "descriptor": "Endoderm", "descriptor_ui": "D004707", "major_topic": false }, { "descriptor": "Gene Expression Regulation, Developmental", "descriptor_ui": "D018507", "major_topic": false }, { "descriptor": "Gene Knockdown Techniques", "descriptor_ui": "D055785", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Immediate-Early Proteins", "descriptor_ui": "D017874", "major_topic": false }, { "descriptor": "Immunoblotting", "descriptor_ui": "D015151", "major_topic": false }, { "descriptor": "In Situ Hybridization", "descriptor_ui": "D017403", "major_topic": false }, { "descriptor": "In Situ Nick-End Labeling", "descriptor_ui": "D020287", "major_topic": false }, { "descriptor": "Luciferases", "descriptor_ui": "D008156", "major_topic": false }, { "descriptor": "Mesoderm", "descriptor_ui": "D008648", "major_topic": false }, { "descriptor": "Microarray Analysis", "descriptor_ui": "D046228", "major_topic": false }, { "descriptor": "Mitochondrial Proteins", "descriptor_ui": "D024101", "major_topic": false }, { "descriptor": "Multiprotein Complexes", "descriptor_ui": "D046912", "major_topic": false }, { "descriptor": "NF-kappa B", "descriptor_ui": "D016328", "major_topic": false }, { "descriptor": "Oligonucleotides", "descriptor_ui": "D009841", "major_topic": false }, { "descriptor": "Phosphatidylinositol 3-Kinases", "descriptor_ui": "D019869", "major_topic": false }, { "descriptor": "Protein Serine-Threonine Kinases", "descriptor_ui": "D017346", "major_topic": false }, { "descriptor": "Reverse Transcriptase Polymerase Chain Reaction", "descriptor_ui": "D020133", "major_topic": false }, { "descriptor": "Serum-Glucocorticoid Regulated Kinases", "descriptor_ui": "D000099184", "major_topic": false }, { "descriptor": "Xenopus laevis", "descriptor_ui": "D014982", "major_topic": false }, { "descriptor": "Xenopus Proteins", "descriptor_ui": "D029867", "major_topic": false } ], "publication": { "conference_name": null, "date": "2011 Jan 18", "date_precision": "day", "issue": "156", "normalized_date": "2011-01-18", "pages": "ra2", "proceedings_title": null, "publisher": "", "title": "Science signaling", "volume": "4", "year": 2011 }, "ssbd": { "database": [], "repository": [] }, "title": "The kinase SGK1 in the endoderm and mesoderm promotes ectodermal survival by down-regulating components of the death-inducing signaling complex.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "", "classifications": [ { "id": "Fujita", "label": "Group Fujita", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Mei-Ling", "last_name": "Zheng", "name": null }, { "creator_type": "author", "first_name": "Katsumasa", "last_name": "Fujita", "name": null }, { "creator_type": "author", "first_name": "Wei-Qiang", "last_name": "Chen", "name": null }, { "creator_type": "author", "first_name": "Nicholas Isaac", "last_name": "Smith", "name": null }, { "creator_type": "author", "first_name": "Xuan-Ming", "last_name": "Duan", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Kawata", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/cbic.201000593" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "21161969" } }, "mesh": [ { "descriptor": "Carbazoles", "descriptor_ui": "D002227", "major_topic": false }, { "descriptor": "Carbocyanines", "descriptor_ui": "D002232", "major_topic": false }, { "descriptor": "Fluorescent Dyes", "descriptor_ui": "D005456", "major_topic": false }, { "descriptor": "HeLa Cells", "descriptor_ui": "D006367", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Intracellular Space", "descriptor_ui": "D042541", "major_topic": false }, { "descriptor": "Microscopy, Fluorescence", "descriptor_ui": "D008856", "major_topic": false }, { "descriptor": "Nonlinear Dynamics", "descriptor_ui": "D017711", "major_topic": true }, { "descriptor": "Staining and Labeling", "descriptor_ui": "D013194", "major_topic": false } ], "publication": { "conference_name": null, "date": "2011 Jan 3", "date_precision": "day", "issue": "1", "normalized_date": "2011-01-03", "pages": "52-55", "proceedings_title": null, "publisher": "", "title": "Chembiochem : a European journal of chemical biology", "volume": "12", "year": 2011 }, "ssbd": { "database": [], "repository": [] }, "title": "Comparison of staining selectivity for subcellular structures by carbazole-based cyanine probes in nonlinear optical microscopy.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "We investigated actions of uridine 5'-triphosphate (UTP) in rat aorta, cerebral and mesenteric arteries, and their single myocytes. UTP (>/=10 microM) elicited an inward-rectifying current strongly reminiscent of activation of P2X(1) receptor, and a similar current was also induced by alpha,beta-methylene adenosine 5'-triphosphate (ATP) (>/=100 nM). UTP desensitized alpha,beta-methylene ATP-evoked current, and vice versa. The UTP-activated current was insensitive to G-protein modulators, TRPC3 inhibitors, or TRPC3 antibody, but was sensitive to P2-receptor inhibitors or P2X(1)-receptor antibody. Both UTP (1 mM) and alpha,beta-methylene ATP (10 microM) elicited similar conductance single channel activities. UTP (>/=10 microM) provoked a dose-dependent contraction of de-endothelialized aortic ring preparation consisting of phasic and tonic components. Removal of extracellular Ca(2+) or bath-applied 2',3'-O-(2,4,6-trinitrophenyl)-ATP (TNP-ATP) (30 microM) or nifedipine (10 microM) completely inhibited the phasic contraction while only partially reducing the tonic one. The tonic contraction was almost completely abolished by additional application of thapsigargin (2 microM). Similar biphasic rises in [Ca(2+)](i) were also evoked by UTP in rat aortic myocytes. In contrast to the low expression of TRPC3, significant expression of P2X(1) receptor was detected in all arteries by RT-PCR and immunoblotting, and its localization was limited to plasma membrane of myocytes as indicated by immunohistochemistry. These results suggest that UTP dually activates P2X(1)-like and P2Y receptors, but not TRPC3.", "classifications": [ { "id": "Nishida", "label": "Group Nishida", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Megumi", "last_name": "Sugihara", "name": null }, { "creator_type": "author", "first_name": "Hiromitsu", "last_name": "Morita", "name": null }, { "creator_type": "author", "first_name": "Miho", "last_name": "Matsuda", "name": null }, { "creator_type": "author", "first_name": "Hisanori", "last_name": "Umebayashi", "name": null }, { "creator_type": "author", "first_name": "Shunichi", "last_name": "Kajioka", "name": null }, { "creator_type": "author", "first_name": "Shinichi", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Motohiro", "last_name": "Nishida", "name": null }, { "creator_type": "author", "first_name": "Ryosuke", "last_name": "Inoue", "name": null }, { "creator_type": "author", "first_name": "Toshiko", "last_name": "Futatsuki", "name": null }, { "creator_type": "author", "first_name": "Jun", "last_name": "Yamazaki", "name": null }, { "creator_type": "author", "first_name": "Yasuo", "last_name": "Mori", "name": null }, { "creator_type": "author", "first_name": "Ryuji", "last_name": "Inoue", "name": null }, { "creator_type": "author", "first_name": "Yushi", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Kihachiro", "last_name": "Abe", "name": null }, { "creator_type": "author", "first_name": "Masato", "last_name": "Hirata", "name": null } ], "identifiers": { "doi": { "normalized": "10.1254/jphs.10281fp" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "21350312" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Aorta", "descriptor_ui": "D001011", "major_topic": false }, { "descriptor": "Arteries", "descriptor_ui": "D001158", "major_topic": false }, { "descriptor": "Calcium", "descriptor_ui": "D002118", "major_topic": false }, { "descriptor": "Constriction", "descriptor_ui": "D003250", "major_topic": false }, { "descriptor": "Extracellular Space", "descriptor_ui": "D005110", "major_topic": false }, { "descriptor": "In Vitro Techniques", "descriptor_ui": "D066298", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Muscle Contraction", "descriptor_ui": "D009119", "major_topic": false }, { "descriptor": "Patch-Clamp Techniques", "descriptor_ui": "D018408", "major_topic": false }, { "descriptor": "Purinergic P2 Receptor Agonists", "descriptor_ui": "D058910", "major_topic": false }, { "descriptor": "Purinergic P2 Receptor Antagonists", "descriptor_ui": "D058919", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Rats, Sprague-Dawley", "descriptor_ui": "D017207", "major_topic": false }, { "descriptor": "Receptors, Purinergic P2", "descriptor_ui": "D018048", "major_topic": false }, { "descriptor": "RNA", "descriptor_ui": "D012313", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": true }, { "descriptor": "TRPC Cation Channels", "descriptor_ui": "D050052", "major_topic": false }, { "descriptor": "Uridine Triphosphate", "descriptor_ui": "D014544", "major_topic": false } ], "publication": { "conference_name": null, "date": "2011", "date_precision": "year", "issue": "3", "normalized_date": "2011", "pages": "293-308", "proceedings_title": null, "publisher": "", "title": "Journal of pharmacological sciences", "volume": "115", "year": 2011 }, "ssbd": { "database": [], "repository": [] }, "title": "Dual signaling pathways of arterial constriction by extracellular uridine 5'-triphosphate in the rat.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Background: Most diseases are thought to arise from interactions between environmental factors and the host genotype. To detect gene–environment interactions in the development of lifestyle-related diseases, and especially cancer, the Japan Multi-institutional Collaborative Cohort (J-MICC) Study was launched in 2005. Methods: We initiated a cross-sectional study to examine associations of genotypes with lifestyle and clinical factors, as assessed by questionnaires and medical examinations. The 4519 subjects were selected from among participants in the J-MICC Study in 10 areas throughout Japan. In total, 108 polymorphisms were chosen and genotyped using the Invader assay. Results: The study group comprised 2124 men and 2395 women with a mean age of 55.8 ± 8.9 years (range, 35–69 years) at baseline. Among the 108 polymorphisms examined, 4 were not polymorphic in our study population. Among the remaining 104 polymorphisms, most variations were common (minor allele frequency ≥0.05 for 96 polymorphisms). The allele frequencies in this population were comparable with those in the HapMap-JPT data set for 45 Japanese from Tokyo. Only 5 of 88 polymorphisms showed allele-frequency differences greater than 0.1. Of the 108 polymorphisms, 32 showed a highly significant difference in minor allele frequency among the study areas (P < 0.001). Conclusions: This comprehensive data collection on lifestyle and clinical factors will be useful for elucidating gene–environment interactions. In addition, it is likely to be an informative reference tool, as free access to genotype data for a large Japanese population is not readily available.", "classifications": [ { "id": "Tanaka", "label": "Group Tanaka", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Kenji", "last_name": "Wakai", "name": null }, { "creator_type": "author", "first_name": "Nobuyuki", "last_name": "Hamajima", "name": null }, { "creator_type": "author", "first_name": "Rieko", "last_name": "Okada", "name": null }, { "creator_type": "author", "first_name": "Mariko", "last_name": "Naito", "name": null }, { "creator_type": "author", "first_name": "Emi", "last_name": "Morita", "name": null }, { "creator_type": "author", "first_name": "Asahi", "last_name": "Hishida", "name": null }, { "creator_type": "author", "first_name": "Sayo", "last_name": "Kawai", "name": null }, { "creator_type": "author", "first_name": "Kazuko", "last_name": "Nishio", "name": null }, { "creator_type": "author", "first_name": "Guang", "last_name": "Yin", "name": null }, { "creator_type": "author", "first_name": "Yatami", "last_name": "Asai", "name": null }, { "creator_type": "author", "first_name": "Keitaro", "last_name": "Matsuo", "name": null }, { "creator_type": "author", "first_name": "Satoyo", "last_name": "Hosono", "name": null }, { "creator_type": "author", "first_name": "Hidemi", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Miki", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Takakazu", "last_name": "Kawase", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Kazuo", "last_name": "Tajima", "name": null }, { "creator_type": "author", "first_name": "Keitaro", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Yasuki", "last_name": "Higaki", "name": null }, { "creator_type": "author", "first_name": "Megumi", "last_name": "Hara", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Imaizumi", "name": null }, { "creator_type": "author", "first_name": "Naoto", "last_name": "Taguchi", "name": null }, { "creator_type": "author", "first_name": "Kazuyo", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Hinako", "last_name": "Nanri", "name": null }, { "creator_type": "author", "first_name": "Tatsuhiko", "last_name": "Sakamoto", "name": null }, { "creator_type": "author", "first_name": "Mikako", "last_name": "Horita", "name": null }, { "creator_type": "author", "first_name": "Koichi", "last_name": "Shinchi", "name": null }, { "creator_type": "author", "first_name": "Yoshikuni", "last_name": "Kita", "name": null }, { "creator_type": "author", "first_name": "Tanvir Chowdhury", "last_name": "Turin", "name": null }, { "creator_type": "author", "first_name": "Nahid", "last_name": "Rumana", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Matsui", "name": null }, { "creator_type": "author", "first_name": "Katsuyuki", "last_name": "Miura", "name": null }, { "creator_type": "author", "first_name": "Hirotsugu", "last_name": "Ueshima", "name": null }, { "creator_type": "author", "first_name": "Naoyuki", "last_name": "Takashima", "name": null }, { "creator_type": "author", "first_name": "Yasuyuki", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Sadao", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Ryosuke", "last_name": "Ando", "name": null }, { "creator_type": "author", "first_name": "Akihiro", "last_name": "Hosono", "name": null }, { "creator_type": "author", "first_name": "Nahomi", "last_name": "Imaeda", "name": null }, { "creator_type": "author", "first_name": "Kiyoshi", "last_name": "Shibata", "name": null }, { "creator_type": "author", "first_name": "Chiho", "last_name": "Goto", "name": null }, { "creator_type": "author", "first_name": "Nami", "last_name": "Hattori", "name": null }, { "creator_type": "author", "first_name": "Mitsuru", "last_name": "Fukatsu", "name": null }, { "creator_type": "author", "first_name": "Tamaki", "last_name": "Yamada", "name": null }, { "creator_type": "author", "first_name": "Shinkan", "last_name": "Tokudome", "name": null }, { "creator_type": "author", "first_name": "Toshiro", "last_name": "Takezaki", "name": null }, { "creator_type": "author", "first_name": "Hideshi", "last_name": "Niimura", "name": null }, { "creator_type": "author", "first_name": "Kazuyo", "last_name": "Hirasada", "name": null }, { "creator_type": "author", "first_name": "Akihiko", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Masaya", "last_name": "Tatebo", "name": null }, { "creator_type": "author", "first_name": "Shin", "last_name": "Ogawa", "name": null }, { "creator_type": "author", "first_name": "Noriko", "last_name": "Tsunematsu", "name": null }, { "creator_type": "author", "first_name": "Shirabe", "last_name": "Chiba", "name": null }, { "creator_type": "author", "first_name": "Haruo", "last_name": "Mikami", "name": null }, { "creator_type": "author", "first_name": "Suminori", "last_name": "Kono", "name": null }, { "creator_type": "author", "first_name": "Keizo", "last_name": "Ohnaka", "name": null }, { "creator_type": "author", "first_name": "Ryoichi", "last_name": "Takayanagi", "name": null }, { "creator_type": "author", "first_name": "Yoshiyuki", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Etsuko", "last_name": "Ozaki", "name": null }, { "creator_type": "author", "first_name": "Masako", "last_name": "Shigeta", "name": null }, { "creator_type": "author", "first_name": "Nagato", "last_name": "Kuriyama", "name": null }, { "creator_type": "author", "first_name": "Aya", "last_name": "Yoshikawa", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Matsui", "name": null }, { "creator_type": "author", "first_name": "Isao", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Kaoru", "last_name": "Inoue", "name": null }, { "creator_type": "author", "first_name": "Kotaro", "last_name": "Ozasa", "name": null }, { "creator_type": "author", "first_name": "Satoko", "last_name": "Mitani", "name": null }, { "creator_type": "author", "first_name": "Kokichi", "last_name": "Arisawa", "name": null }, { "creator_type": "author", "first_name": "Hirokazu", "last_name": "Uemura", "name": null }, { "creator_type": "author", "first_name": "Mineyoshi", "last_name": "Hiyoshi", "name": null }, { "creator_type": "author", "first_name": "Hidenobu", "last_name": "Takami", "name": null }, { "creator_type": "author", "first_name": "Miwa", "last_name": "Yamaguchi", "name": null }, { "creator_type": "author", "first_name": "Mariko", "last_name": "Nakamoto", "name": null }, { "creator_type": "author", "first_name": "Hideo", "last_name": "Takeda", "name": null }, { "creator_type": "author", "first_name": "Michiaki", "last_name": "Kubo", "name": null }, { "creator_type": "author", "first_name": "Hideo", "last_name": "Tanaka", "name": null } ], "identifiers": { "doi": { "normalized": "10.2188/jea.je20100139" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "21467728" } }, "mesh": [ { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Cohort Studies", "descriptor_ui": "D015331", "major_topic": false }, { "descriptor": "Cross-Sectional Studies", "descriptor_ui": "D003430", "major_topic": false }, { "descriptor": "Environment", "descriptor_ui": "D004777", "major_topic": true }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Gene Frequency", "descriptor_ui": "D005787", "major_topic": false }, { "descriptor": "Genotype", "descriptor_ui": "D005838", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Japan", "descriptor_ui": "D007564", "major_topic": false }, { "descriptor": "Life Style", "descriptor_ui": "D008019", "major_topic": true }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Polymorphism, Genetic", "descriptor_ui": "D011110", "major_topic": false } ], "publication": { "conference_name": null, "date": "2011", "date_precision": "year", "issue": "3", "normalized_date": "2011", "pages": "223-235", "proceedings_title": null, "publisher": "", "title": "Journal of Epidemiology", "volume": "21", "year": 2011 }, "ssbd": { "database": [], "repository": [] }, "title": "Profile of Participants and Genotype Distributions of 108 Polymorphisms in a Cross-Sectional Study of Associations of Genotypes With Lifestyle and Clinical Factors: A Project in the Japan Multi-Institutional Collaborative Cohort (J-MICC) Study.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Dendritic trees influence synaptic integration and neuronal excitability, yet appear to develop in rather arbitrary patterns. Using electron microscopy and serial reconstructions, we analyzed the dendritic trees of four morphologically distinct neocortical interneuron subtypes to reveal two underlying organizational principles common to all. First, cross-sectional areas at any given point within a dendrite were proportional to the summed length of all dendritic segments distal to that point. Consistent with this observation, total cross-sectional area was almost perfectly conserved at bifurcation points. Second, dendritic cross-sections became progressively more elliptical at more proximal, larger diameter, dendritic locations. Finally, computer simulations revealed that these conserved morphological features limit distance dependent filtering of somatic EPSPs and facilitate distribution of somatic depolarization into all dendritic compartments. Because these features were shared by all interneurons studied, they may represent common organizational principles underlying the otherwise diverse morphology of dendritic trees.", "classifications": [ { "id": "Mochizuki", "label": "Group Mochizuki", "parent": "Eiraku", "type": "group" }, { "id": "Eiraku", "label": "Team Eiraku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yoshiyuki", "last_name": "Kubota", "name": null }, { "creator_type": "author", "first_name": "Fuyuki", "last_name": "Karube", "name": null }, { "creator_type": "author", "first_name": "Masaki", "last_name": "Nomura", "name": null }, { "creator_type": "author", "first_name": "Allan T.", "last_name": "Gulledge", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Mochizuki", "name": null }, { "creator_type": "author", "first_name": "Andreas", "last_name": "Schertel", "name": null }, { "creator_type": "author", "first_name": "Yasuo", "last_name": "Kawaguchi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/srep00089" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "22355608" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cerebral Cortex", "descriptor_ui": "D002540", "major_topic": false }, { "descriptor": "Dendrites", "descriptor_ui": "D003712", "major_topic": true }, { "descriptor": "Immunohistochemistry", "descriptor_ui": "D007150", "major_topic": false }, { "descriptor": "Interneurons", "descriptor_ui": "D007395", "major_topic": false }, { "descriptor": "Microscopy, Electron, Scanning", "descriptor_ui": "D008855", "major_topic": false }, { "descriptor": "Microtubules", "descriptor_ui": "D008870", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Rats, Wistar", "descriptor_ui": "D017208", "major_topic": false } ], "publication": { "conference_name": null, "date": "2011", "date_precision": "year", "issue": "", "normalized_date": "2011", "pages": "", "proceedings_title": null, "publisher": "", "title": "Scientific Reports", "volume": "1", "year": 2011 }, "ssbd": { "database": [], "repository": [] }, "title": "Conserved properties of dendritic trees in four cortical interneuron subtypes.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and Burkitt lymphoma (iDLBCL/BL) is a newly categorized lymphoma in the WHO Classification of Tumors of Haematopoietic and Lymphoid Tissues v4. This lymphoma has characteristics of both DLBCL and BL, morphologically and genetically. We report a case with therapy-resistant iDLBCL/BL, which used to be categorized as BL in the WHO Classification v3. This case showed strong BCL2 staining, otherwise exhibiting features of BL. The case was treated with intensive chemotherapy containing high-dose methotrexate, cyclophosphamide, and cytarabine. However, soon after the chemotherapy, the lymphoma relapsed in the central nervous system and was resistant to whole-brain radiation therapy and allogeneic stem cell transplantation. The patient died 37 days after the transplantation. The clinical course was different from that of typical BL in terms of resistance to intensive chemotherapy, in agreement with the characteristics of iDLBCL/BL.", "classifications": [ { "id": "Nishikii", "label": "Group Nishikii", "parent": "Shintaku", "type": "group" }, { "id": "Shintaku", "label": "Team Shintaku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Naoki", "last_name": "Kurita", "name": null }, { "creator_type": "author", "first_name": "Hidekazu", "last_name": "Nishikii", "name": null }, { "creator_type": "author", "first_name": "Rie", "last_name": "Nakamoto", "name": null }, { "creator_type": "author", "first_name": "Naoya", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Yuzuru", "last_name": "Kondo", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Okoshi", "name": null }, { "creator_type": "author", "first_name": "Kazumi", "last_name": "Suzukawa", "name": null }, { "creator_type": "author", "first_name": "Yuichi", "last_name": "Hasegawa", "name": null }, { "creator_type": "author", "first_name": "Yasuhisa", "last_name": "Yokoyama", "name": null }, { "creator_type": "author", "first_name": "Masayuki", "last_name": "Noguchi", "name": null }, { "creator_type": "author", "first_name": "Shigeru", "last_name": "Chiba", "name": null } ], "identifiers": { "doi": { "normalized": "10.3960/jslrt.51.37" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "21628859" } }, "mesh": [ { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Antineoplastic Combined Chemotherapy Protocols", "descriptor_ui": "D000971", "major_topic": false }, { "descriptor": "Burkitt Lymphoma", "descriptor_ui": "D002051", "major_topic": false }, { "descriptor": "Cyclophosphamide", "descriptor_ui": "D003520", "major_topic": false }, { "descriptor": "Cytarabine", "descriptor_ui": "D003561", "major_topic": false }, { "descriptor": "Fatal Outcome", "descriptor_ui": "D017809", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Lymphoma, B-Cell", "descriptor_ui": "D016393", "major_topic": false }, { "descriptor": "Lymphoma, Large B-Cell, Diffuse", "descriptor_ui": "D016403", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Methotrexate", "descriptor_ui": "D008727", "major_topic": false }, { "descriptor": "Proto-Oncogene Proteins c-bcl-2", "descriptor_ui": "D019253", "major_topic": false } ], "publication": { "conference_name": null, "date": "2011", "date_precision": "year", "issue": "1", "normalized_date": "2011", "pages": "37-42", "proceedings_title": null, "publisher": "", "title": "Journal of clinical and experimental hematopathology : JCEH", "volume": "51", "year": 2011 }, "ssbd": { "database": [], "repository": [] }, "title": "A highly therapy-resistant case of B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and Burkitt lymphoma showing strong BCL2 staining, otherwise indistinguishable from Burkitt lymphoma.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The prognosis of adult Burkitt lymphoma (BL) has improved in western countries since the introduction of high-dose methotrexate (HD-MTX)-containing chemotherapy. Here we analyzed nine consecutive Japanese patients diagnosed with BL at our institution. All except for the three elderly (> 70 years) patients were treated with a regimen including 13 g/m(2) HD-MTX in total, divided into 3 cycles. The median follow-up period was 56 months (range 38-118). All the nine patients achieved complete remission and have not shown any disease progression, including the three elderly patients who received reduced doses or alternative treatments. These observations suggest that chemotherapy including 13 g/m(2) HD-MTX in total is tolerable and effective in Japanese adult BL patients aged < 70 and that BL is curable even if developed in those who are > 70 years.", "classifications": [ { "id": "Nishikii", "label": "Group Nishikii", "parent": "Shintaku", "type": "group" }, { "id": "Shintaku", "label": "Team Shintaku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Hidekazu", "last_name": "Nishikii", "name": null }, { "creator_type": "author", "first_name": "Naoya", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Yuzuru", "last_name": "Kondo", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Okoshi", "name": null }, { "creator_type": "author", "first_name": "Kazumi", "last_name": "Suzukawa", "name": null }, { "creator_type": "author", "first_name": "Yuichi", "last_name": "Hasegawa", "name": null }, { "creator_type": "author", "first_name": "Yasuhisa", "last_name": "Yokoyama", "name": null }, { "creator_type": "author", "first_name": "Mamiko", "last_name": "Sakata-Yanagimoto", "name": null }, { "creator_type": "author", "first_name": "Terukazu", "last_name": "Enami", "name": null }, { "creator_type": "author", "first_name": "Masayuki", "last_name": "Noguchi", "name": null }, { "creator_type": "author", "first_name": "Shigeru", "last_name": "Chiba", "name": null } ], "identifiers": { "doi": { "normalized": "10.3960/jslrt.51.109" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "22104309" } }, "mesh": [ { "descriptor": "Adolescent", "descriptor_ui": "D000293", "major_topic": false }, { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Aged, 80 and over", "descriptor_ui": "D000369", "major_topic": false }, { "descriptor": "Antineoplastic Combined Chemotherapy Protocols", "descriptor_ui": "D000971", "major_topic": false }, { "descriptor": "Burkitt Lymphoma", "descriptor_ui": "D002051", "major_topic": false }, { "descriptor": "Cyclophosphamide", "descriptor_ui": "D003520", "major_topic": false }, { "descriptor": "Cytarabine", "descriptor_ui": "D003561", "major_topic": false }, { "descriptor": "Doxorubicin", "descriptor_ui": "D004317", "major_topic": false }, { "descriptor": "Etoposide", "descriptor_ui": "D005047", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Japan", "descriptor_ui": "D007564", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Methotrexate", "descriptor_ui": "D008727", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Prognosis", "descriptor_ui": "D011379", "major_topic": false }, { "descriptor": "Retrospective Studies", "descriptor_ui": "D012189", "major_topic": false }, { "descriptor": "Treatment Outcome", "descriptor_ui": "D016896", "major_topic": false }, { "descriptor": "Vincristine", "descriptor_ui": "D014750", "major_topic": false }, { "descriptor": "Young Adult", "descriptor_ui": "D055815", "major_topic": false } ], "publication": { "conference_name": null, "date": "2011", "date_precision": "year", "issue": "2", "normalized_date": "2011", "pages": "109-114", "proceedings_title": null, "publisher": "", "title": "Journal of clinical and experimental hematopathology : JCEH", "volume": "51", "year": 2011 }, "ssbd": { "database": [], "repository": [] }, "title": "Treatment outcome of adult Burkitt Lymphoma in Japanese patients with modified LMB protocol : a single center retrospective analysis.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Although mammalian neurogenesis is mostly completed by the perinatal period, new neurons are continuously generated in the subventricular zone of the lateral ventricle and the subgranular zone of the hippocampal dentate gyrus. Since the discovery of adult neurogenesis, many extensive studies have been performed on various aspects of adult neurogenesis, including proliferation and fate-specification of adult neural stem cells, and the migration, maturation and synaptic integration of newly born neurons. Furthermore, recent research has shed light on the intensive contribution of adult neurogenesis to olfactory-related and hippocampus-mediated brain functions. The field of adult neurogenesis progressed tremendously thanks to technical advances that facilitate the identification and selective manipulation of newly born neurons among billions of pre-existing neurons in the adult central nervous system. In this review, we introduce recent advances in the methodologies for visualizing newly generated neurons and manipulating neurogenesis in the adult brain. Particularly, the application of site-specific recombinases and Tet inducible system in combination with transgenic or gene targeting strategy is discussed in further detail.", "classifications": [ { "id": "Imayoshi", "label": "Group Imayoshi", "parent": "Imayoshi", "type": "group" }, { "id": "Imayoshi", "label": "Team Imayoshi", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Itaru", "last_name": "Imayoshi", "name": null }, { "creator_type": "author", "first_name": "Masayuki", "last_name": "Sakamoto", "name": null }, { "creator_type": "author", "first_name": "Ryoichiro", "last_name": "Kageyama", "name": null } ], "identifiers": { "doi": { "normalized": "10.3389/fnins.2011.00064" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "21562606" } }, "mesh": [], "publication": { "conference_name": null, "date": "2011", "date_precision": "year", "issue": "", "normalized_date": "2011", "pages": "", "proceedings_title": null, "publisher": "", "title": "Frontiers in Neuroscience", "volume": "5", "year": 2011 }, "ssbd": { "database": [], "repository": [] }, "title": "Genetic Methods to Identify and Manipulate Newly Born Neurons in the Adult Brain.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Dendrite arborization patterns are critical determinants of neuronal connectivity and integration. Planar and highly branched dendrites of the cerebellar Purkinje cell receive specific topographical projections from two major afferent pathways; a single climbing fiber axon from the inferior olive that extend along Purkinje dendrites, and parallel fiber axons of granule cells that contact vertically to the plane of dendrites. It has been believed that murine Purkinje cell dendrites extend in a single parasagittal plane in the molecular layer after the cell polarity is determined during the early postnatal development. By three-dimensional confocal analysis of growing Purkinje cells, we observed that mouse Purkinje cells underwent dynamic dendritic remodeling during circuit maturation in the third postnatal week. After dendrites were polarized and flattened in the early second postnatal week, dendritic arbors gradually expanded in multiple sagittal planes in the molecular layer by intensive growth and branching by the third postnatal week. Dendrites then became confined to a single plane in the fourth postnatal week. Multiplanar Purkinje cells in the third week were often associated by ectopic climbing fibers innervating nearby Purkinje cells in distinct sagittal planes. The mature monoplanar arborization was disrupted in mutant mice with abnormal Purkinje cell connectivity and motor discoordination. The dendrite remodeling was also impaired by pharmacological disruption of normal afferent activity during the second or third postnatal week. Our results suggest that the monoplanar arborization of Purkinje cells is coupled with functional development of the cerebellar circuitry.", "classifications": [ { "id": "Eiraku", "label": "Group Eiraku", "parent": "Eiraku", "type": "group" }, { "id": "Eiraku", "label": "Team Eiraku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Megumi", "last_name": "Kaneko", "name": null }, { "creator_type": "author", "first_name": "Kazuhiko", "last_name": "Yamaguchi", "name": null }, { "creator_type": "author", "first_name": "Mototsugu", "last_name": "Eiraku", "name": null }, { "creator_type": "author", "first_name": "Motohiko", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Norio", "last_name": "Takata", "name": null }, { "creator_type": "author", "first_name": "Yoshimoto", "last_name": "Kiyohara", "name": null }, { "creator_type": "author", "first_name": "Masayoshi", "last_name": "Mishina", "name": null }, { "creator_type": "author", "first_name": "Hajime", "last_name": "Hirase", "name": null }, { "creator_type": "author", "first_name": "Tsutomu", "last_name": "Hashikawa", "name": null }, { "creator_type": "author", "first_name": "Mineko", "last_name": "Kengaku", "name": null } ], "identifiers": { "doi": { "normalized": "10.1371/journal.pone.0020108" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "21655286" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cerebellum", "descriptor_ui": "D002531", "major_topic": false }, { "descriptor": "Dendrites", "descriptor_ui": "D003712", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Immunohistochemistry", "descriptor_ui": "D007150", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Microscopy, Confocal", "descriptor_ui": "D018613", "major_topic": false }, { "descriptor": "Pregnancy", "descriptor_ui": "D011247", "major_topic": false }, { "descriptor": "Purkinje Cells", "descriptor_ui": "D011689", "major_topic": false } ], "publication": { "conference_name": null, "date": "2011", "date_precision": "year", "issue": "5", "normalized_date": "2011", "pages": "", "proceedings_title": null, "publisher": "", "title": "PLoS ONE", "volume": "6", "year": 2011 }, "ssbd": { "database": [], "repository": [] }, "title": "Remodeling of Monoplanar Purkinje Cell Dendrites during Cerebellar Circuit Formation.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "MicroRNAs (miRNAs) are important regulators of gene expression that control physiological and pathological processes. A global reduction in miRNA abundance and function is a general trait of human cancers, playing a causal role in the transformed phenotype. Here, we sought to newly identify genes involved in the regulation of miRNA function by performing a genetic screen using reporter constructs that measure miRNA function and retrovirus-based random gene disruption. Of the six genes identified, RACK1, which encodes “receptor for activated protein kinase C” (RACK1), was confirmed to be necessary for full miRNA function. RACK1 binds to KH-type splicing regulatory protein (KSRP), a member of the Dicer complex, and is required for the recruitment of mature miRNAs to the RNA-induced silencing complex (RISC). In addition, RACK1 expression was frequently found to be reduced in hepatocellular carcinoma. These findings suggest the involvement of RACK1 in miRNA function and indicate that reduced miRNA function, due to decreased expression of RACK1, may have pathologically relevant roles in liver cancers.", "classifications": [ { "id": "Takekawa", "label": "Group Takekawa", "parent": "Takekawa", "type": "group" }, { "id": "Takekawa", "label": "Team Takekawa", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Motoyuki", "last_name": "Otsuka", "name": null }, { "creator_type": "author", "first_name": "Akemi", "last_name": "Takata", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Yoshikawa", "name": null }, { "creator_type": "author", "first_name": "Kentaro", "last_name": "Kojima", "name": null }, { "creator_type": "author", "first_name": "Takahiro", "last_name": "Kishikawa", "name": null }, { "creator_type": "author", "first_name": "Chikako", "last_name": "Shibata", "name": null }, { "creator_type": "author", "first_name": "Mutsuhiro", "last_name": "Takekawa", "name": null }, { "creator_type": "author", "first_name": "Haruhiko", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Masao", "last_name": "Omata", "name": null }, { "creator_type": "author", "first_name": "Kazuhiko", "last_name": "Koike", "name": null } ], "identifiers": { "doi": { "normalized": "10.1371/journal.pone.0024359" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "21935400" } }, "mesh": [ { "descriptor": "Argonaute Proteins", "descriptor_ui": "D060565", "major_topic": false }, { "descriptor": "Carcinoma, Hepatocellular", "descriptor_ui": "D006528", "major_topic": false }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "GTP-Binding Proteins", "descriptor_ui": "D019204", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Immunoprecipitation", "descriptor_ui": "D047468", "major_topic": false }, { "descriptor": "MicroRNAs", "descriptor_ui": "D035683", "major_topic": false }, { "descriptor": "Neoplasm Proteins", "descriptor_ui": "D009363", "major_topic": false }, { "descriptor": "Receptors for Activated C Kinase", "descriptor_ui": "D000075370", "major_topic": false }, { "descriptor": "Receptors, Cell Surface", "descriptor_ui": "D011956", "major_topic": false }, { "descriptor": "RNA-Binding Proteins", "descriptor_ui": "D016601", "major_topic": false }, { "descriptor": "Trans-Activators", "descriptor_ui": "D015534", "major_topic": false } ], "publication": { "conference_name": null, "date": "2011", "date_precision": "year", "issue": "9", "normalized_date": "2011", "pages": "", "proceedings_title": null, "publisher": "", "title": "PLoS ONE", "volume": "6", "year": 2011 }, "ssbd": { "database": [], "repository": [] }, "title": "Receptor for Activated Protein Kinase C: Requirement for Efficient MicroRNA Function and Reduced Expression in Hepatocellular Carcinoma.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Heterotrimeric G proteins are composed of alpha, beta, and gamma subunits. G proteins can be activated by a large number of cell-surface hepathelical receptors and can transduce signals from these receptors to various intracellular signaling molecules. When G protein-coupled receptors are bound by their cognate ligand, interaction with specific subtypes of G protein leads to dissociation of the alpha subunit of the heterotrimeric G protein from the betagamma dimer, and both Galpha-GTP and Gbetagamma are capable of initiating their own signal transduction pathways. G proteins are functionally divided into four groups based on the nature of alpha subunit into G(s), G(i), G(q), and G(1)(2) families. The members of the G(1)(2) subfamily are G(1)(2) and G(1)(3). Increasing evidence indicates that G(1)(2)/(1)(3) proteins play critical roles in various physiological functions. G(1)(2) and G(1)(3) regulate the small GTPase Rho through modulation of guanine nucleotide exchange factor (RhoGEF) activity to regulate various cellular responses, such as cytoskeletal changes and cell growth. Therefore, Rho activity can often represent a sensitive marker of G(1)(2)/(1)(3) activity. Here, we describe the Rho activation assay to monitor the activity of G(1)(2)/(1)(3) proteins.", "classifications": [ { "id": "Nishida", "label": "Group Nishida", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Michio", "last_name": "Nakaya", "name": null }, { "creator_type": "author", "first_name": "Mina", "last_name": "Ohba", "name": null }, { "creator_type": "author", "first_name": "Motohiro", "last_name": "Nishida", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Kurose", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/978-1-61779-126-0_17" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "21607865" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Apoptosis Regulatory Proteins", "descriptor_ui": "D051017", "major_topic": false }, { "descriptor": "GTP-Binding Protein alpha Subunits, G12-G13", "descriptor_ui": "D044365", "major_topic": false }, { "descriptor": "GTP-Binding Proteins", "descriptor_ui": "D019204", "major_topic": false }, { "descriptor": "Guanine Nucleotide Exchange Factors", "descriptor_ui": "D020662", "major_topic": false }, { "descriptor": "Intracellular Signaling Peptides and Proteins", "descriptor_ui": "D047908", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Myocytes, Cardiac", "descriptor_ui": "D032383", "major_topic": false }, { "descriptor": "Protein Binding", "descriptor_ui": "D011485", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Receptors, G-Protein-Coupled", "descriptor_ui": "D043562", "major_topic": false }, { "descriptor": "Rho Guanine Nucleotide Exchange Factors", "descriptor_ui": "D064067", "major_topic": false } ], "publication": { "conference_name": null, "date": "2011", "date_precision": "year", "issue": "", "normalized_date": "2011", "pages": "317-327", "proceedings_title": null, "publisher": "", "title": "Methods in molecular biology (Clifton, N.J.)", "volume": "746", "year": 2011 }, "ssbd": { "database": [], "repository": [] }, "title": "Determining the activation of rho as an index of receptor coupling to G(1)(2)/(1)(3) proteins.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The adult mammalian brain is composed of distinct regions with specialized roles including regulation of circadian clocks, feeding, sleep/awake, and seasonal rhythms. To find quantitative differences of expression among such various brain regions, we conducted the BrainStars (B*) project, in which we profiled the genome-wide expression of approximately 50 small brain regions, including sensory centers, and centers for motion, time, memory, fear, and feeding. To avoid confounds from temporal differences in gene expression, we sampled each region every 4 hours for 24 hours, and pooled the samples for DNA-microarray assays. Therefore, we focused on spatial differences in gene expression. We used informatics to identify candidate genes with expression changes showing high or low expression in specific regions. We also identified candidate genes with stable expression across brain regions that can be used as new internal control genes, and ligand-receptor interactions of neurohormones and neurotransmitters. Through these analyses, we found 8,159 multi-state genes, 2,212 regional marker gene candidates for 44 small brain regions, 915 internal control gene candidates, and 23,864 inferred ligand-receptor interactions. We also found that these sets include well-known genes as well as novel candidate genes that might be related to specific functions in brain regions. We used our findings to develop an integrated database (http://brainstars.org/) for exploring genome-wide expression in the adult mouse brain, and have made this database openly accessible. These new resources will help accelerate the functional analysis of the mammalian brain and the elucidation of its regulatory network systems.", "classifications": [ { "id": "Nikaido", "label": "Group Nikaido", "parent": "Fujiwara", "type": "group" }, { "id": "Fujiwara", "label": "Team Fujiwara", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Takeya", "last_name": "Kasukawa", "name": null }, { "creator_type": "author", "first_name": "Koh-hei", "last_name": "Masumoto", "name": null }, { "creator_type": "author", "first_name": "Itoshi", "last_name": "Nikaido", "name": null }, { "creator_type": "author", "first_name": "Mamoru", "last_name": "Nagano", "name": null }, { "creator_type": "author", "first_name": "Kenichiro D.", "last_name": "Uno", "name": null }, { "creator_type": "author", "first_name": "Kaori", "last_name": "Tsujino", "name": null }, { "creator_type": "author", "first_name": "Carina", "last_name": "Hanashima", "name": null }, { "creator_type": "author", "first_name": "Yasufumi", "last_name": "Shigeyoshi", "name": null }, { "creator_type": "author", "first_name": "Hiroki R.", "last_name": "Ueda", "name": null } ], "identifiers": { "doi": { "normalized": "10.1371/journal.pone.0023228" }, "pmcid": { "normalized": "PMC3155528" }, "pmid": { "normalized": "21858037" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Brain", "descriptor_ui": "D001921", "major_topic": false }, { "descriptor": "Cluster Analysis", "descriptor_ui": "D016000", "major_topic": false }, { "descriptor": "Gene Expression Profiling", "descriptor_ui": "D020869", "major_topic": false }, { "descriptor": "Gene Regulatory Networks", "descriptor_ui": "D053263", "major_topic": false }, { "descriptor": "In Situ Hybridization", "descriptor_ui": "D017403", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred BALB C", "descriptor_ui": "D008807", "major_topic": false }, { "descriptor": "Models, Genetic", "descriptor_ui": "D008957", "major_topic": false }, { "descriptor": "Oligonucleotide Array Sequence Analysis", "descriptor_ui": "D020411", "major_topic": false }, { "descriptor": "Transcriptome", "descriptor_ui": "D059467", "major_topic": true } ], "publication": { "conference_name": null, "date": "2011", "date_precision": "year", "issue": "8", "normalized_date": "2011", "pages": "e23228", "proceedings_title": null, "publisher": "", "title": "PloS one", "volume": "6", "year": 2011 }, "ssbd": { "database": [], "repository": [] }, "title": "Quantitative expression profile of distinct functional regions in the adult mouse brain.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Background: Cancer cell responses to chemotherapeutic agents vary, and this may reflect different defects in DNA repair, cell-cycle checkpoints, and apoptosis control. Cytometry analysis only quantifies dye-incorporation to examine DNA content and does not reflect the biological complexity of the cell cycle in drug discovery screens. Results: Using population and time-lapse imaging analyses of cultured immortalized cells expressing a new version of the fluorescent cell-cycle indicator, Fucci (Fluorescent Ubiquitination-based Cell Cycle Indicator), we found great diversity in the cell-cycle alterations induced by two anticancer drugs. When treated with etoposide, an inhibitor of DNA topoisomerase II, HeLa and NMuMG cells halted at the G2/M checkpoint. HeLa cells remained there, but NMuMG cells then overrode the checkpoint and underwent nuclear mis-segregation or avoided the checkpoint and entered the endoreplication cycle in a drug concentration dependent manner. In contrast, an inhibitor of Cdk4 led to G1 arrest or endoreplication in NMuMG cells depending upon the initial cell-cycle phase of drug exposure. Conclusions: Drug-induced cell cycle modulation varied not only between different cell types or following treatment with different drugs, but also between cells treated with different concentrations of the same drug or following drug addition during different phases of the cell cycle. By combining cytometry analysis with the Fucci probe, we have developed a novel assay that fully integrates the complexity of cell cycle regulation into drug discovery screens. This assay system will represent a powerful drug-discovery tool for the development of the next generation of anti-cancer therapies.", "classifications": [ { "id": "Sawano", "label": "Group Sawano", "parent": "Shintaku", "type": "group" }, { "id": "Shintaku", "label": "Team Shintaku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Asako", "last_name": "Sakaue-Sawano", "name": null }, { "creator_type": "author", "first_name": "Tamiyo", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Ohtawa", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Miyawaki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1186/1471-2121-12-2" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "21226962" } }, "mesh": [ { "descriptor": "Antineoplastic Agents, Phytogenic", "descriptor_ui": "D000972", "major_topic": false }, { "descriptor": "Carbazoles", "descriptor_ui": "D002227", "major_topic": false }, { "descriptor": "Cell Cycle", "descriptor_ui": "D002453", "major_topic": false }, { "descriptor": "Cell Cycle Proteins", "descriptor_ui": "D018797", "major_topic": false }, { "descriptor": "Cell Division", "descriptor_ui": "D002455", "major_topic": false }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Cell Nucleus", "descriptor_ui": "D002467", "major_topic": false }, { "descriptor": "Cell Proliferation", "descriptor_ui": "D049109", "major_topic": false }, { "descriptor": "Chromosome Segregation", "descriptor_ui": "D020090", "major_topic": false }, { "descriptor": "Cyclin-Dependent Kinase 4", "descriptor_ui": "D051358", "major_topic": false }, { "descriptor": "DNA Replication", "descriptor_ui": "D004261", "major_topic": false }, { "descriptor": "DNA Topoisomerases, Type II", "descriptor_ui": "D004250", "major_topic": false }, { "descriptor": "Etoposide", "descriptor_ui": "D005047", "major_topic": false }, { "descriptor": "G2 Phase", "descriptor_ui": "D016195", "major_topic": false }, { "descriptor": "Green Fluorescent Proteins", "descriptor_ui": "D049452", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Luminescent Proteins", "descriptor_ui": "D008164", "major_topic": false }, { "descriptor": "Red Fluorescent Protein", "descriptor_ui": "D000097573", "major_topic": false }, { "descriptor": "S Phase", "descriptor_ui": "D016196", "major_topic": false }, { "descriptor": "Time-Lapse Imaging", "descriptor_ui": "D059008", "major_topic": false } ], "publication": { "conference_name": null, "date": "2011", "date_precision": "year", "issue": "", "normalized_date": "2011", "pages": "2", "proceedings_title": null, "publisher": "", "title": "BMC Cell Biology", "volume": "12", "year": 2011 }, "ssbd": { "database": [], "repository": [] }, "title": "Drug-induced cell cycle modulation leading to cell-cycle arrest, nuclear mis-segregation, or endoreplication.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Background: We previously developed the DBRF-MEGN (difference-based regulation finding-minimum equivalent gene network) method, which deduces the most parsimonious signed directed graphs (SDGs) consistent with expression profiles of single-gene deletion mutants. However, until the present study, we have not presented the details of the method's algorithm or a proof of the algorithm. Results: We describe in detail the algorithm of the DBRF-MEGN method and prove that the algorithm deduces all of the exact solutions of the most parsimonious SDGs consistent with expression profiles of gene deletion mutants. Conclusions: The DBRF-MEGN method provides all of the exact solutions of the most parsimonious SDGs consistent with expression profiles of gene deletion mutants.", "classifications": [ { "id": "Onami", "label": "Group Onami", "parent": "Fujiwara", "type": "group" }, { "id": "Fujiwara", "label": "Team Fujiwara", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Koji", "last_name": "Kyoda", "name": null }, { "creator_type": "author", "first_name": "Kotaro", "last_name": "Baba", "name": null }, { "creator_type": "author", "first_name": "Hiroaki", "last_name": "Kitano", "name": null }, { "creator_type": "author", "first_name": "Shuichi", "last_name": "Onami", "name": null } ], "identifiers": { "doi": { "normalized": "10.1186/1751-0473-6-12" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "21699737" } }, "mesh": [], "publication": { "conference_name": null, "date": "2011", "date_precision": "year", "issue": "", "normalized_date": "2011", "pages": "12", "proceedings_title": null, "publisher": "", "title": "Source Code for Biology and Medicine", "volume": "6", "year": 2011 }, "ssbd": { "database": [], "repository": [] }, "title": "A proof of the DBRF-MEGN method, an algorithm for deducing minimum equivalent gene networks.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Heart failure is a major cause of death in developed countries, and the development of an epoch-making cure is desired from the viewpoint for improving the quality of life and reducing the medical cost of the patient. The importance of neurohumoral factors, such as angiotensin (Ang) II and catecholamine, for the progression of heart failure has been supported by a variety of evidence. These agonists stimulate seven transmembrane-spanning receptors that are coupled to heterotrimeric GTP-binding proteins (G proteins). Using specific pharmacological tools to assess the involvement of G protein signaling pathways, we have revealed that alpha subunit of G(q) (Galpha(q)) activates Ca(2+)-dependent hypertrophic signaling through diacylglycerol-activated transient receptor potential canonical (TRPC) channels (TRPC3 and TRPC6: TRPC3/6). In contrast, activation of Galpha(12) family proteins in cardiomyocytes confers pressure overload-induced cardiac fibrosis via stimulation of purinergic P2Y(6) receptors induced by extracellular nucleotides released from cardiomyocytes. In fact, direct or indirect inhibition of TRPC3/6 or P2Y(6) receptors attenuates pressure overload-induced cardiac dysfunction. These findings will provide a new insight into the molecular mechanisms underlying pathogenesis of heart failure.", "classifications": [ { "id": "Nishida", "label": "Group Nishida", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Motohiro", "last_name": "Nishida", "name": null } ], "identifiers": { "doi": { "normalized": "10.1254/jphs.11r05cp" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "21821969" } }, "mesh": [ { "descriptor": "Angiotensin II", "descriptor_ui": "D000804", "major_topic": false }, { "descriptor": "Calcium Channels", "descriptor_ui": "D015220", "major_topic": false }, { "descriptor": "Diglycerides", "descriptor_ui": "D004075", "major_topic": false }, { "descriptor": "Disease Progression", "descriptor_ui": "D018450", "major_topic": false }, { "descriptor": "Heart Failure", "descriptor_ui": "D006333", "major_topic": false }, { "descriptor": "Heterotrimeric GTP-Binding Proteins", "descriptor_ui": "D020962", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false } ], "publication": { "conference_name": null, "date": "2011", "date_precision": "year", "issue": "1", "normalized_date": "2011", "pages": "1-5", "proceedings_title": null, "publisher": "", "title": "Journal of pharmacological sciences", "volume": "117", "year": 2011 }, "ssbd": { "database": [], "repository": [] }, "title": "Roles of heterotrimeric GTP-binding proteins in the progression of heart failure.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Extracellularly released adenosine triphosphate (ATP) modulates sensory signaling in the spinal cord. We analyzed the spatiotemporal profiles of P2X receptor-mediated neuronal and glial processing of sensory signals and the distribution of P2X receptor subunits in the rat dorsal horn. Voltage imaging of spinal cord slices revealed that extracellularly applied ATP (5-500 muM), which was degraded to adenosine and acting on P1 receptors, inhibited depolarizing signals and that it also enhanced long-lasting slow depolarization, which was potentiated after ATP was washed out. This post-ATP rebound potentiation was mediated by P2X receptors and was more prominent in the deep than in the superficial layer. Patch clamp recording of neurons in the superficial layer revealed long-lasting enhancement of depolarization by ATP through P2X receptors during the slow repolarization phase at a single neuron level. This depolarization pattern was different from that in voltage imaging, which reflects both neuronal and glial activities. By immunohistochemistry, P2X(1) and P2X(3) subunits were detected in neuropils in the superficial layer. The P2X(5) subunit was found in neuronal somata. The P2X(6) subunit was widely expressed in neuropils in the whole gray matter except for the dorsal superficial layer. Astrocytes expressed the P2X(7) subunit. These findings indicate that extracellular ATP is degraded into adenosine and prevents overexcitation of the sensory system, and that ATP acts on pre- and partly on postsynaptic neuronal P2X receptors and enhances synaptic transmission, predominantly in the deep layer. Astrocytes are involved in sensitization of sensory network activity more importantly in the superficial than in the deep layer.", "classifications": [ { "id": "Yokota", "label": "Group Yokota", "parent": "Enomoto", "type": "group" }, { "id": "Enomoto", "label": "Team Enomoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Ryoma", "last_name": "Aoyama", "name": null }, { "creator_type": "author", "first_name": "Yasumasa", "last_name": "Okada", "name": null }, { "creator_type": "author", "first_name": "Shigefumi", "last_name": "Yokota", "name": null }, { "creator_type": "author", "first_name": "Yutaka", "last_name": "Yasui", "name": null }, { "creator_type": "author", "first_name": "Kentaro", "last_name": "Fukuda", "name": null }, { "creator_type": "author", "first_name": "Yoshio", "last_name": "Shinozaki", "name": null }, { "creator_type": "author", "first_name": "Hideaki", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Masaya", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Kazuhiro", "last_name": "Chiba", "name": null }, { "creator_type": "author", "first_name": "Yukihiko", "last_name": "Yasui", "name": null }, { "creator_type": "author", "first_name": "Fusao", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Yoshiaki", "last_name": "Toyama", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.pain.2011.05.014" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "21669492" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Brain Chemistry", "descriptor_ui": "D001923", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Neuroglia", "descriptor_ui": "D009457", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Posterior Horn Cells", "descriptor_ui": "D020671", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Rats, Wistar", "descriptor_ui": "D017208", "major_topic": false }, { "descriptor": "Receptors, Purinergic P2", "descriptor_ui": "D018048", "major_topic": false }, { "descriptor": "Receptors, Purinergic P2X1", "descriptor_ui": "D058474", "major_topic": false }, { "descriptor": "Receptors, Purinergic P2X3", "descriptor_ui": "D058477", "major_topic": false }, { "descriptor": "Receptors, Purinergic P2X5", "descriptor_ui": "D058485", "major_topic": false }, { "descriptor": "Receptors, Purinergic P2X7", "descriptor_ui": "D058486", "major_topic": false }, { "descriptor": "Sensory Receptor Cells", "descriptor_ui": "D011984", "major_topic": false }, { "descriptor": "Spinal Cord", "descriptor_ui": "D013116", "major_topic": false }, { "descriptor": "Time Factors", "descriptor_ui": "D013997", "major_topic": false } ], "publication": { "conference_name": null, "date": "2011 Sep", "date_precision": "unknown", "issue": "9", "normalized_date": null, "pages": "2085-2097", "proceedings_title": null, "publisher": "", "title": "Pain", "volume": "152", "year": 2011 }, "ssbd": { "database": [], "repository": [] }, "title": "Spatiotemporal and anatomical analyses of P2X receptor-mediated neuronal and glial processing of sensory signals in the rat dorsal horn.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "EHMT2 is a histone lysine methyltransferase localized in euchromatin regions and acting as a corepressor for specific transcription factors. Although the role of EHMT2 in transcriptional regulation has been well documented, the pathologic consequences of its dysfunction in human disease have not been well understood. Here, we describe important roles of EHMT2 in human carcinogenesis. Expression levels of EHMT2 are significantly elevated in human bladder carcinomas compared with nonneoplastic bladder tissues (P < .0001) in real-time polymerase chain reaction analysis. Complementary DNA microarray analysis also revealed its overexpression in various types of cancer. The reduction of EHMT2 expression by small interfering RNAs resulted in the suppression of the growth of cancer cells and possibly caused apoptotic cell death in cancer cells. Importantly, we show that EHMT2 can suppress transcription of the SIAH1 gene by binding to its promoter region (-293 to +51) and by methylating lysine 9 of histone H3. Furthermore, an EHMT2-specific inhibitor, BIX-01294, significantly suppressed the growth of cancer cells. Our results suggest that dysregulation of EHMT2 plays an important role in the growth regulation of cancer cells, and further functional studies may affirm the importance of EHMT2 as a promising therapeutic target for various types of cancer.", "classifications": [ { "id": "Hamamoto", "label": "Group Hamamoto", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Hyun-Soo", "last_name": "Cho", "name": null }, { "creator_type": "author", "first_name": "John D.", "last_name": "Kelly", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Hayami", "name": null }, { "creator_type": "author", "first_name": "Gouji", "last_name": "Toyokawa", "name": null }, { "creator_type": "author", "first_name": "Masahi", "last_name": "Takawa", "name": null }, { "creator_type": "author", "first_name": "Masanori", "last_name": "Yoshimatsu", "name": null }, { "creator_type": "author", "first_name": "Tatsuhiko", "last_name": "Tsunoda", "name": null }, { "creator_type": "author", "first_name": "Helen I.", "last_name": "Field", "name": null }, { "creator_type": "author", "first_name": "David E.", "last_name": "Neal", "name": null }, { "creator_type": "author", "first_name": "Bruce Aj", "last_name": "Ponder", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Ryuji", "last_name": "Hamamoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1593/neo.11512" }, "pmcid": { "normalized": "PMC3156658" }, "pmid": { "normalized": "21847359" } }, "mesh": [ { "descriptor": "Apoptosis", "descriptor_ui": "D017209", "major_topic": false }, { "descriptor": "Azepines", "descriptor_ui": "D001381", "major_topic": false }, { "descriptor": "Cell Line, Transformed", "descriptor_ui": "D002461", "major_topic": false }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Cell Proliferation", "descriptor_ui": "D049109", "major_topic": false }, { "descriptor": "Gene Expression Regulation, Neoplastic", "descriptor_ui": "D015972", "major_topic": true }, { "descriptor": "HEK293 Cells", "descriptor_ui": "D057809", "major_topic": false }, { "descriptor": "Histocompatibility Antigens", "descriptor_ui": "D006649", "major_topic": false }, { "descriptor": "Histone-Lysine N-Methyltransferase", "descriptor_ui": "D011495", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Neoplasms", "descriptor_ui": "D009369", "major_topic": false }, { "descriptor": "Nuclear Proteins", "descriptor_ui": "D009687", "major_topic": false }, { "descriptor": "Quinazolines", "descriptor_ui": "D011799", "major_topic": false }, { "descriptor": "Seven in Absentia Proteins", "descriptor_ui": "D000098563", "major_topic": false }, { "descriptor": "Ubiquitin-Protein Ligases", "descriptor_ui": "D044767", "major_topic": false } ], "publication": { "conference_name": null, "date": "2011 Aug", "date_precision": "unknown", "issue": "8", "normalized_date": null, "pages": "676-684", "proceedings_title": null, "publisher": "", "title": "Neoplasia (New York, N.Y.)", "volume": "13", "year": 2011 }, "ssbd": { "database": [], "repository": [] }, "title": "Enhanced expression of EHMT2 is involved in the proliferation of cancer cells through negative regulation of SIAH1.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is an inherited systemic disease characterized by renal cyst expansion, resulting in renal failure. With the progression of renal damage, the accumulation of uremic compounds is recently reported to subsequently cause further renal damage and hypertension. Finding uremic toxins and sensitive markers for detecting the early stage of ADPKD is necessary to clarify its pathophysiological process and to prevent its progression. The aim of this study was to analyze the profile of uremic retention solutes of ADPKD by capillary electrophoresis-mass spectrometry (CE-MS) using the Han:SPRD rat model. METHODS: Two hundred and ninety-seven cations and 190 anions were comprehensively analyzed by CE-MS in Han:SPRD rats and control rats. RESULTS: We found 21 cations and 19 anions that accumulated significantly in the heterozygous (Cy/+) ADPKD rat model compared with control rats. Among the compounds, increases in 5-methyl-2'-deoxycytidine, glucosamine, ectoine, allantoate, alpha-hydroxybenzoate, phenaceturate and 3-phenylpropionate and decreases in 2-deoxycytidine, decanoate and 10-hydroxydecanoate were newly identified in the ADPKD Cy/+ rats. CONCLUSION: We identified uremic retention solutes in ADPKD Cy/+ rats. Compounds related to ADPKD could be useful markers for detecting the early stage of ADPKD.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Takafumi", "last_name": "Toyohara", "name": null }, { "creator_type": "author", "first_name": "Takehiro", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Yasutoshi", "last_name": "Akiyama", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Yoshihara", "name": null }, { "creator_type": "author", "first_name": "Yoichi", "last_name": "Takeuchi", "name": null }, { "creator_type": "author", "first_name": "Eikan", "last_name": "Mishima", "name": null }, { "creator_type": "author", "first_name": "Koichi", "last_name": "Kikuchi", "name": null }, { "creator_type": "author", "first_name": "Chitose", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Masayuki", "last_name": "Tanemoto", "name": null }, { "creator_type": "author", "first_name": "Sadayoshi", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Shizuko", "last_name": "Nagao", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Takaaki", "last_name": "Abe", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/s10157-011-0467-4" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "21695416" } }, "mesh": [ { "descriptor": "Aconitic Acid", "descriptor_ui": "D000156", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Disease Models, Animal", "descriptor_ui": "D004195", "major_topic": false }, { "descriptor": "Electrophoresis, Capillary", "descriptor_ui": "D019075", "major_topic": false }, { "descriptor": "Hippurates", "descriptor_ui": "D006626", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Indican", "descriptor_ui": "D007200", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mass Spectrometry", "descriptor_ui": "D013058", "major_topic": false }, { "descriptor": "Metabolomics", "descriptor_ui": "D055432", "major_topic": true }, { "descriptor": "Polycystic Kidney, Autosomal Dominant", "descriptor_ui": "D016891", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Renal Insufficiency", "descriptor_ui": "D051437", "major_topic": false } ], "publication": { "conference_name": null, "date": "2011 Oct", "date_precision": "unknown", "issue": "5", "normalized_date": null, "pages": "676-687", "proceedings_title": null, "publisher": "", "title": "Clinical and experimental nephrology", "volume": "15", "year": 2011 }, "ssbd": { "database": [], "repository": [] }, "title": "Metabolomic profiling of the autosomal dominant polycystic kidney disease rat model.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Transition routes of propagating pulses in the Gray-Scott model from oscillatory to chaotic motion are investigated by numerical studies. Global bifurcation of the Gray-Scott model gives us information about the onset mechanism of transient dynamics, such as the splitting and extinction of pulses. However, the instability mechanism of oscillatory pulses has not been clarified, even numerically. Global bifurcation analysis of time periodic oscillatory traveling pulses, called traveling breathers, enables us to find chaotic motions of oscillatory pulse solutions. Two types of transitions to chaos, namely, period-doubling sequences and breakdown of quasiperiodic solutions, are found near the bifurcation points of traveling breathers.", "classifications": [ { "id": "Nagayama", "label": "Group Nagayama", "parent": "Fujiwara", "type": "group" }, { "id": "Fujiwara", "label": "Team Fujiwara", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Masaaki", "last_name": "Yadome", "name": null }, { "creator_type": "author", "first_name": "Kei-Ichi", "last_name": "Ueda", "name": null }, { "creator_type": "author", "first_name": "Masaharu", "last_name": "Nagayama", "name": null } ], "identifiers": { "doi": { "normalized": "10.1103/physreve.83.056207" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "21728630" } }, "mesh": [ { "descriptor": "Motion", "descriptor_ui": "D009038", "major_topic": true }, { "descriptor": "Nonlinear Dynamics", "descriptor_ui": "D017711", "major_topic": true }, { "descriptor": "Periodicity", "descriptor_ui": "D010507", "major_topic": false } ], "publication": { "conference_name": null, "date": "2011 May", "date_precision": "unknown", "issue": "5 Pt 2", "normalized_date": null, "pages": "056207", "proceedings_title": null, "publisher": "", "title": "Physical review. E, Statistical, nonlinear, and soft matter physics", "volume": "83", "year": 2011 }, "ssbd": { "database": [], "repository": [] }, "title": "Chaotic motion of propagating pulses in the Gray-Scott model.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "We discovered that the PF1549 gene in Pyrococcus furiosus encodes a very heat-stable RNA 3'-terminal phosphate cyclase (Pf-Rtc). Although all previously reported Rtc proteins are ATP-dependent enzymes, we found that Pf-Rtc requires GTP for its cyclase activity at 95 degrees C. Low-level activation of the enzyme was also observed in the presence of dGTP but not other dNTPs, indicating that the guanine base is very important for Pf-Rtc activity. We analyzed a series of GTP analogues and found that the conversion from GTP to GMP is important for Pf-Rtc activity and that an excess of GMP inhibits this activity. Gel-shift analysis clearly showed that the RNA-binding activity of Pf-Rtc is totally dependent on the linear form of the 3'-terminal phosphate, with an apparent K(d) value of 20 nm at 95 degrees C. Furthermore, we found that Pf-Rtc may contribute to GTP-dependent RNA ligation activity through the PF0027 protein (a 2'-5' RNA ligase-like protein in P. furiosus). The possible roles of Pf-Rtc and the importance of terminal phosphate structures in RNA are discussed.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Asako", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Kaori", "last_name": "Igarashi", "name": null }, { "creator_type": "author", "first_name": "Kanako", "last_name": "Takesue", "name": null }, { "creator_type": "author", "first_name": "Masaru", "last_name": "Tomita", "name": null }, { "creator_type": "author", "first_name": "Akio", "last_name": "Kanai", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/j.1365-2443.2011.01561.x" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "22074260" } }, "mesh": [ { "descriptor": "Amino Acid Sequence", "descriptor_ui": "D000595", "major_topic": false }, { "descriptor": "Cloning, Molecular", "descriptor_ui": "D003001", "major_topic": false }, { "descriptor": "Electrophoretic Mobility Shift Assay", "descriptor_ui": "D024202", "major_topic": false }, { "descriptor": "Escherichia coli", "descriptor_ui": "D004926", "major_topic": false }, { "descriptor": "Guanosine Triphosphate", "descriptor_ui": "D006160", "major_topic": false }, { "descriptor": "Hot Temperature", "descriptor_ui": "D006358", "major_topic": false }, { "descriptor": "Kinetics", "descriptor_ui": "D007700", "major_topic": false }, { "descriptor": "Ligases", "descriptor_ui": "D008025", "major_topic": false }, { "descriptor": "Molecular Sequence Data", "descriptor_ui": "D008969", "major_topic": false }, { "descriptor": "Phosphates", "descriptor_ui": "D010710", "major_topic": false }, { "descriptor": "Plasmids", "descriptor_ui": "D010957", "major_topic": false }, { "descriptor": "Polynucleotide Ligases", "descriptor_ui": "D011118", "major_topic": false }, { "descriptor": "Pyrococcus furiosus", "descriptor_ui": "D020027", "major_topic": false }, { "descriptor": "Recombinant Proteins", "descriptor_ui": "D011994", "major_topic": false }, { "descriptor": "RNA", "descriptor_ui": "D012313", "major_topic": false }, { "descriptor": "Sequence Homology, Amino Acid", "descriptor_ui": "D017386", "major_topic": false }, { "descriptor": "Transformation, Bacterial", "descriptor_ui": "D014169", "major_topic": false } ], "publication": { "conference_name": null, "date": "2011 Dec", "date_precision": "unknown", "issue": "12", "normalized_date": null, "pages": "1190-1199", "proceedings_title": null, "publisher": "", "title": "Genes to cells : devoted to molecular & cellular mechanisms", "volume": "16", "year": 2011 }, "ssbd": { "database": [], "repository": [] }, "title": "GTP-dependent RNA 3'-terminal phosphate cyclase from the hyperthermophilic archaeon Pyrococcus furiosus.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "A variety of cellular functions are robust even to substantial intrinsic and extrinsic noise in intracellular reactions and the environment that could be strong enough to impair or limit them. In particular, of substantial importance is cellular decision-making in which a cell chooses a fate or behavior on the basis of information conveyed in noisy external signals. For robust decoding, the crucial step is filtering out the noise inevitably added during information transmission. As a minimal and optimal implementation of such an information decoding process, the autocatalytic phosphorylation and autocatalytic dephosphorylation (aPadP) cycle was recently proposed. Here, we analyze the dynamical properties of the aPadP cycle in detail. We describe the dynamical roles of the stationary and short-term responses in determining the efficiency of information decoding and clarify the optimality of the threshold value of the stationary response and its information-theoretical meaning. Furthermore, we investigate the robustness of the aPadP cycle against the receptor inactivation time and intrinsic noise. Finally, we discuss the relationship among information decoding with information-dependent actions, bet-hedging and network modularity.", "classifications": [ { "id": "Kobayashi", "label": "Group Kobayashi", "parent": "Wakamoto", "type": "group" }, { "id": "Wakamoto", "label": "Team Wakamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Tetsuya J.", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Kamimura", "name": null } ], "identifiers": { "doi": { "normalized": "10.1088/1478-3975/8/5/055007" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "21832798" } }, "mesh": [ { "descriptor": "Catalysis", "descriptor_ui": "D002384", "major_topic": false }, { "descriptor": "Cell Physiological Phenomena", "descriptor_ui": "D002468", "major_topic": true }, { "descriptor": "Models, Biological", "descriptor_ui": "D008954", "major_topic": true }, { "descriptor": "Phosphorylation", "descriptor_ui": "D010766", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Stochastic Processes", "descriptor_ui": "D013269", "major_topic": false } ], "publication": { "conference_name": null, "date": "2011 Oct", "date_precision": "unknown", "issue": "5", "normalized_date": null, "pages": "055007", "proceedings_title": null, "publisher": "", "title": "Physical biology", "volume": "8", "year": 2011 }, "ssbd": { "database": [], "repository": [] }, "title": "Dynamics of intracellular information decoding.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The development of technologies that allow the stable delivery of large genomic DNA fragments in mammalian systems is important for genetic studies as well as for applications in gene therapy. DNA transposons have emerged as flexible and efficient molecular vehicles to mediate stable cargo transfer. However, the ability to carry DNA fragments >10 kb is limited in most DNA transposons. Here, we show that the DNA transposon piggyBac can mobilize 100-kb DNA fragments in mouse embryonic stem (ES) cells, making it the only known transposon with such a large cargo capacity. The integrity of the cargo is maintained during transposition, the copy number can be controlled and the inserted giant transposons express the genomic cargo. Furthermore, these 100-kb transposons can also be excised from the genome without leaving a footprint. The development of piggyBac as a large cargo vector will facilitate a wider range of genetic and genomic applications.", "classifications": [ { "id": "Yusa", "label": "Group Yusa", "parent": "Eiraku", "type": "group" }, { "id": "Eiraku", "label": "Team Eiraku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Meng Amy", "last_name": "Li", "name": null }, { "creator_type": "author", "first_name": "Daniel J.", "last_name": "Turner", "name": null }, { "creator_type": "author", "first_name": "Zemin", "last_name": "Ning", "name": null }, { "creator_type": "author", "first_name": "Kosuke", "last_name": "Yusa", "name": null }, { "creator_type": "author", "first_name": "Qi", "last_name": "Liang", "name": null }, { "creator_type": "author", "first_name": "Sabine", "last_name": "Eckert", "name": null }, { "creator_type": "author", "first_name": "Lena", "last_name": "Rad", "name": null }, { "creator_type": "author", "first_name": "Tomas W.", "last_name": "Fitzgerald", "name": null }, { "creator_type": "author", "first_name": "Nancy L.", "last_name": "Craig", "name": null }, { "creator_type": "author", "first_name": "Allan", "last_name": "Bradley", "name": null } ], "identifiers": { "doi": { "normalized": "10.1093/nar/gkr764" }, "pmcid": { "normalized": "PMC3239208" }, "pmid": { "normalized": "21948799" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "DNA Transposable Elements", "descriptor_ui": "D004251", "major_topic": true }, { "descriptor": "Embryonic Stem Cells", "descriptor_ui": "D053595", "major_topic": false }, { "descriptor": "Genetic Loci", "descriptor_ui": "D056426", "major_topic": false }, { "descriptor": "Genetic Vectors", "descriptor_ui": "D005822", "major_topic": true }, { "descriptor": "Genome", "descriptor_ui": "D016678", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Hydrolases", "descriptor_ui": "D006867", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false } ], "publication": { "conference_name": null, "date": "2011 Dec", "date_precision": "unknown", "issue": "22", "normalized_date": null, "pages": "e148", "proceedings_title": null, "publisher": "", "title": "Nucleic acids research", "volume": "39", "year": 2011 }, "ssbd": { "database": [], "repository": [] }, "title": "Mobilization of giant piggyBac transposons in the mouse genome.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The ERK (extracellular signal-regulated kinase) MAPK (mitogen-activated protein kinase) cascade (Raf-MEK-ERK) mediates mitogenic signalling, and is frequently hyperactivated by Ras oncogenes in human cancer. The entire range of activities of multifunctional Ras in carcinogenesis remains elusive. Here we report that the ERK pathway is downregulated by MEK (MAPK-ERK kinase) SUMOylation, which is inhibited by oncogenic Ras. MEK SUMOylation blocked ERK activation by disrupting the specific docking interaction between MEK and ERK. Expression of un-SUMOylatable MEK enhanced ERK activation, cell differentiation, proliferation and malignant transformation by oncogenic ErbB2 or Raf, but not by active Ras. Interestingly, MEK SUMOylation was abrogated in cancer cells harbouring Ras mutations. Oncogenic Ras inhibits MEK SUMOylation by impairing the function of the MEKK1 MAPKKK as a SUMO-E3 ligase specific for MEK. Furthermore, forced enhancement of MEK SUMOylation suppressed Ras-induced cell transformation. Thus, oncogenic Ras efficiently activates the ERK pathway both by activating Raf and by inhibiting MEK SUMOylation, thereby inducing carcinogenesis.", "classifications": [ { "id": "Takekawa", "label": "Group Takekawa", "parent": "Takekawa", "type": "group" }, { "id": "Takekawa", "label": "Team Takekawa", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yuji", "last_name": "Kubota", "name": null }, { "creator_type": "author", "first_name": "Pauline", "last_name": "O'Grady", "name": null }, { "creator_type": "author", "first_name": "Haruo", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Mutsuhiro", "last_name": "Takekawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/ncb2169" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "21336309" } }, "mesh": [ { "descriptor": "Amino Acid Sequence", "descriptor_ui": "D000595", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "Cell Membrane", "descriptor_ui": "D002462", "major_topic": false }, { "descriptor": "Cell Transformation, Neoplastic", "descriptor_ui": "D002471", "major_topic": true }, { "descriptor": "Extracellular Signal-Regulated MAP Kinases", "descriptor_ui": "D048049", "major_topic": false }, { "descriptor": "Gene Expression Regulation, Neoplastic", "descriptor_ui": "D015972", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "MAP Kinase Kinase Kinases", "descriptor_ui": "D020930", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Molecular Sequence Data", "descriptor_ui": "D008969", "major_topic": false }, { "descriptor": "Neoplasms", "descriptor_ui": "D009369", "major_topic": false }, { "descriptor": "NIH 3T3 Cells", "descriptor_ui": "D041681", "major_topic": false }, { "descriptor": "ras Proteins", "descriptor_ui": "D018631", "major_topic": false }, { "descriptor": "Small Ubiquitin-Related Modifier Proteins", "descriptor_ui": "D025841", "major_topic": false } ], "publication": { "conference_name": null, "date": "2011 Mar", "date_precision": "unknown", "issue": "3", "normalized_date": null, "pages": "282-291", "proceedings_title": null, "publisher": "", "title": "Nature cell biology", "volume": "13", "year": 2011 }, "ssbd": { "database": [], "repository": [] }, "title": "Oncogenic Ras abrogates MEK SUMOylation that suppresses the ERK pathway and cell transformation.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND & AIMS: We applied a metabolome profiling approach to serum samples obtained from patients with different liver diseases, to discover noninvasive and reliable biomarkers for rapid-screening diagnosis of liver diseases. METHODS: Using capillary electrophoresis and liquid chromatography mass spectrometry, we analyzed low molecular weight metabolites in a total of 248 serum samples obtained from patients with nine types of liver disease and healthy controls. RESULTS: We found that gamma-glutamyl dipeptides, which were biosynthesized through a reaction with gamma-glutamylcysteine synthetase, were indicative of the production of reduced glutathione, and that measurement of their levels could distinguish among different liver diseases. Multiple logistic regression models facilitated the discrimination between specific and other liver diseases and yielded high areas under receiver-operating characteristic curves. The area under the curve values in training and independent validation data were 0.952 and 0.967 in healthy controls, 0.817 and 0.849 in drug-induced liver injury, 0.754 and 0.763 in asymptomatic hepatitis B virus infection, 0.820 and 0.762 in chronic hepatitis B, 0.972 and 0.895 in hepatitis C with persistently normal alanine transaminase, 0.917 and 0.707 in chronic hepatitis C, 0.803 and 0.993 in cirrhosis type C, and 0.762 and 0.803 in hepatocellular carcinoma, respectively. Several gamma-glutamyl dipeptides also manifested potential for differentiating between nonalcoholic steatohepatitis and simple steatosis. CONCLUSIONS: gamma-Glutamyl dipeptides are novel biomarkers for liver diseases, and varying levels of individual or groups of these peptides have the power to discriminate among different forms of hepatic disease.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Sugimoto", "name": null }, { "creator_type": "author", "first_name": "Masashi", "last_name": "Honma", "name": null }, { "creator_type": "author", "first_name": "Masayo", "last_name": "Mori", "name": null }, { "creator_type": "author", "first_name": "Kaori", "last_name": "Igarashi", "name": null }, { "creator_type": "author", "first_name": "Kasumi", "last_name": "Kashikura", "name": null }, { "creator_type": "author", "first_name": "Satsuki", "last_name": "Ikeda", "name": null }, { "creator_type": "author", "first_name": "Akiyoshi", "last_name": "Hirayama", "name": null }, { "creator_type": "author", "first_name": "Takehito", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Haruhiko", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Motoyuki", "last_name": "Otsuka", "name": null }, { "creator_type": "author", "first_name": "Shoji", "last_name": "Tsuji", "name": null }, { "creator_type": "author", "first_name": "Yutaka", "last_name": "Yatomi", "name": null }, { "creator_type": "author", "first_name": "Tadayuki", "last_name": "Sakuragawa", "name": null }, { "creator_type": "author", "first_name": "Hisayoshi", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Kouei", "last_name": "Nihei", "name": null }, { "creator_type": "author", "first_name": "Takafumi", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Sumio", "last_name": "Kawata", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Masaru", "last_name": "Tomita", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Suematsu", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.jhep.2011.01.031" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "21334394" } }, "mesh": [ { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Biomarkers", "descriptor_ui": "D015415", "major_topic": false }, { "descriptor": "Carcinoma, Hepatocellular", "descriptor_ui": "D006528", "major_topic": false }, { "descriptor": "Diagnosis, Differential", "descriptor_ui": "D003937", "major_topic": false }, { "descriptor": "Dipeptides", "descriptor_ui": "D004151", "major_topic": false }, { "descriptor": "Fatty Liver", "descriptor_ui": "D005234", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Glutamine", "descriptor_ui": "D005973", "major_topic": false }, { "descriptor": "Hepatitis B, Chronic", "descriptor_ui": "D019694", "major_topic": false }, { "descriptor": "Hepatitis C, Chronic", "descriptor_ui": "D019698", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Liver Cirrhosis", "descriptor_ui": "D008103", "major_topic": false }, { "descriptor": "Liver Diseases", "descriptor_ui": "D008107", "major_topic": false }, { "descriptor": "Liver Neoplasms", "descriptor_ui": "D008113", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Metabolomics", "descriptor_ui": "D055432", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Non-alcoholic Fatty Liver Disease", "descriptor_ui": "D065626", "major_topic": false }, { "descriptor": "Oxidative Stress", "descriptor_ui": "D018384", "major_topic": false }, { "descriptor": "Protein Array Analysis", "descriptor_ui": "D040081", "major_topic": false }, { "descriptor": "Reproducibility of Results", "descriptor_ui": "D015203", "major_topic": false } ], "publication": { "conference_name": null, "date": "2011 Oct", "date_precision": "unknown", "issue": "4", "normalized_date": null, "pages": "896-905", "proceedings_title": null, "publisher": "", "title": "Journal of hepatology", "volume": "55", "year": 2011 }, "ssbd": { "database": [], "repository": [] }, "title": "Serum metabolomics reveals gamma-glutamyl dipeptides as biomarkers for discrimination among different forms of liver disease.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Neurogenesis occurs throughout adulthood in the mammalian brain. Newly born neurons are incorporated into the functional networks of both the olfactory bulb and the hippocampal dentate gyrus, and there is growing evidence that adult neurogenesis is important for various brain functions. Continuous neurogenesis is achieved by the coordinated proliferation and differentiation of adult neural stem cells. In this review, we discuss the recent findings concerning the roles of Notch signaling in adult neural stem cells.", "classifications": [ { "id": "Imayoshi", "label": "Group Imayoshi", "parent": "Imayoshi", "type": "group" }, { "id": "Imayoshi", "label": "Team Imayoshi", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Itaru", "last_name": "Imayoshi", "name": null }, { "creator_type": "author", "first_name": "Ryoichiro", "last_name": "Kageyama", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/s12035-011-8186-0" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "21541768" } }, "mesh": [ { "descriptor": "Adult Stem Cells", "descriptor_ui": "D053687", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Neural Stem Cells", "descriptor_ui": "D058953", "major_topic": false }, { "descriptor": "Neurogenesis", "descriptor_ui": "D055495", "major_topic": true }, { "descriptor": "Receptors, Notch", "descriptor_ui": "D051880", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": true } ], "publication": { "conference_name": null, "date": "2011 Aug", "date_precision": "unknown", "issue": "1", "normalized_date": null, "pages": "7-12", "proceedings_title": null, "publisher": "", "title": "Molecular neurobiology", "volume": "44", "year": 2011 }, "ssbd": { "database": [], "repository": [] }, "title": "The role of Notch signaling in adult neurogenesis.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Autophagy is a bulk protein degradation system that likely plays an important role in normal proximal tubule function and recovery from acute ischemic kidney injury. Using conditional Atg5 gene deletion to eliminate autophagy in the proximal tubule, we determined whether autophagy prevents accumulation of damaged proteins and organelles with aging and ischemic renal injury. Autophagy-deficient cells accumulated deformed mitochondria and cytoplasmic inclusions, leading to cellular hypertrophy and eventual degeneration not observed in wildtype controls. In autophagy-deficient mice, I/R injury increased proximal tubule cell apoptosis with accumulation of p62 and ubiquitin positive cytoplasmic inclusions. Compared with control animals, autophagy-deficient mice exhibited significantly greater elevations in serum urea nitrogen and creatinine. These data suggest that autophagy maintains proximal tubule cell homeostasis and protects against ischemic injury. Enhancing autophagy may provide a novel therapeutic approach to minimize acute kidney injury and slow CKD progression.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Tomonori", "last_name": "Kimura", "name": null }, { "creator_type": "author", "first_name": "Yoshitsugu", "last_name": "Takabatake", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Jun-ya", "last_name": "Kaimori", "name": null }, { "creator_type": "author", "first_name": "Isao", "last_name": "Matsui", "name": null }, { "creator_type": "author", "first_name": "Tomoko", "last_name": "Namba", "name": null }, { "creator_type": "author", "first_name": "Harumi", "last_name": "Kitamura", "name": null }, { "creator_type": "author", "first_name": "Fumio", "last_name": "Niimura", "name": null }, { "creator_type": "author", "first_name": "Taiji", "last_name": "Matsusaka", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Hiromi", "last_name": "Rakugi", "name": null }, { "creator_type": "author", "first_name": "Yoshitaka", "last_name": "Isaka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1681/asn.2010070705" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "21493778" } }, "mesh": [ { "descriptor": "Acute Kidney Injury", "descriptor_ui": "D058186", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Autophagy", "descriptor_ui": "D001343", "major_topic": true }, { "descriptor": "Autophagy-Related Protein 5", "descriptor_ui": "D000071187", "major_topic": false }, { "descriptor": "Hypertrophy", "descriptor_ui": "D006984", "major_topic": false }, { "descriptor": "Kidney", "descriptor_ui": "D007668", "major_topic": false }, { "descriptor": "Kidney Tubules, Proximal", "descriptor_ui": "D007687", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Microtubule-Associated Proteins", "descriptor_ui": "D008869", "major_topic": false }, { "descriptor": "Reperfusion Injury", "descriptor_ui": "D015427", "major_topic": false } ], "publication": { "conference_name": null, "date": "2011 May", "date_precision": "unknown", "issue": "5", "normalized_date": null, "pages": "902-913", "proceedings_title": null, "publisher": "", "title": "Journal of the American Society of Nephrology : JASN", "volume": "22", "year": 2011 }, "ssbd": { "database": [], "repository": [] }, "title": "Autophagy Protects the Proximal Tubule from Degeneration and Acute Ischemic Injury.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "From hormonal secretion to gene expression, multicellular dynamics are rich in oscillatory regulation. When organized in space and time, periodic cell-cell signaling can give rise to long-range coordination of gene expression and cell movement in tissues. Lack of synchrony of the oscillations on the other hand can serve as a source of initial divergence of cell fate in stem cells. How properties of individual cells can account for collective rhythmic behaviors at the tissue level remains elusive in most cases. Recently, studies in chemical reactions, synthetic gene circuits, yeast and social amoeba Dictyostelium have greatly enhanced our view of collective oscillations in cell populations. From these relatively simple systems, a unified view of how excitable and oscillatory regulations could be tuned and coupled to give rise to tissue-level oscillations is emerging. The review focuses on recent progress in cyclic adenosine monophosphate oscillations in Dictyostelium and highlights similarities and differences with other systems. We will see that the autonomy of single-cell level oscillations and different ways in which cells are coupled influence how group-level information can be encoded in collective oscillations.", "classifications": [ { "id": "Sawai", "label": "Group Sawai", "parent": "Sawai", "type": "group" }, { "id": "Sawai", "label": "Team Sawai", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Keita", "last_name": "Kamino", "name": null }, { "creator_type": "author", "first_name": "Koichi", "last_name": "Fujimoto", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Sawai", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/j.1440-169x.2011.01266.x" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "21585355" } }, "mesh": [ { "descriptor": "Cells", "descriptor_ui": "D002477", "major_topic": false }, { "descriptor": "Cyclic AMP", "descriptor_ui": "D000242", "major_topic": false }, { "descriptor": "Dictyostelium", "descriptor_ui": "D004023", "major_topic": false } ], "publication": { "conference_name": null, "date": "2011 May", "date_precision": "unknown", "issue": "4", "normalized_date": null, "pages": "503-517", "proceedings_title": null, "publisher": "", "title": "Development, growth & differentiation", "volume": "53", "year": 2011 }, "ssbd": { "database": [], "repository": [] }, "title": "Collective oscillations in developing cells: insights from simple systems.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "A number of histone methyltransferases have been identified and biochemically characterized, but the pathologic roles of their dysfunction in human diseases like cancer are not well understood. Here, we demonstrate that Wolf-Hirschhorn syndrome candidate 1 (WHSC1) plays important roles in human carcinogenesis. Transcriptional levels of this gene are significantly elevated in various types of cancer including bladder and lung cancers. Immunohistochemical analysis using a number of clinical tissues confirmed significant up-regulation of WHSC1 expression in bladder and lung cancer cells at the protein level. Treatment of cancer cell lines with small interfering RNA targeting WHSC1 significantly knocked down its expression and resulted in the suppression of proliferation. Cell cycle analysis by flow cytometry indicated that knockdown of WHSC1 decreased the cell population of cancer cells at the S phase while increasing that at the G(2)/M phase. WHSC1 interacts with some proteins related to the WNT pathway including β-catenin and transcriptionally regulates CCND1, the target gene of the β-catenin/Tcf-4 complex, through histone H3 at lysine 36 trimethylation. This is a novel mechanism for WNT pathway dysregulation in human carcinogenesis, mediated by the epigenetic regulation of histone H3. Because expression levels of WHSC1 are significantly low in most normal tissue types, it should be feasible to develop specific and selective inhibitors targeting the enzyme as antitumor agents that have a minimal risk of adverse reaction.", "classifications": [ { "id": "Hamamoto", "label": "Group Hamamoto", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Gouji", "last_name": "Toyokawa", "name": null }, { "creator_type": "author", "first_name": "Hyun-Soo", "last_name": "Cho", "name": null }, { "creator_type": "author", "first_name": "Ken", "last_name": "Masuda", "name": null }, { "creator_type": "author", "first_name": "Yuka", "last_name": "Yamane", "name": null }, { "creator_type": "author", "first_name": "Masanori", "last_name": "Yoshimatsu", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Hayami", "name": null }, { "creator_type": "author", "first_name": "Masashi", "last_name": "Takawa", "name": null }, { "creator_type": "author", "first_name": "Yukiko", "last_name": "Iwai", "name": null }, { "creator_type": "author", "first_name": "Yataro", "last_name": "Daigo", "name": null }, { "creator_type": "author", "first_name": "Eiju", "last_name": "Tsuchiya", "name": null }, { "creator_type": "author", "first_name": "Tatsuhiko", "last_name": "Tsunoda", "name": null }, { "creator_type": "author", "first_name": "Helen I.", "last_name": "Field", "name": null }, { "creator_type": "author", "first_name": "John D.", "last_name": "Kelly", "name": null }, { "creator_type": "author", "first_name": "David E.", "last_name": "Neal", "name": null }, { "creator_type": "author", "first_name": "Yoshihiko", "last_name": "Maehara", "name": null }, { "creator_type": "author", "first_name": "Bruce Aj", "last_name": "Ponder", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Ryuji", "last_name": "Hamamoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1593/neo.11048" }, "pmcid": { "normalized": "PMC3201566" }, "pmid": { "normalized": "22028615" } }, "mesh": [ { "descriptor": "beta Catenin", "descriptor_ui": "D051176", "major_topic": false }, { "descriptor": "Carcinoma, Non-Small-Cell Lung", "descriptor_ui": "D002289", "major_topic": false }, { "descriptor": "Cell Cycle", "descriptor_ui": "D002453", "major_topic": false }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Cell Proliferation", "descriptor_ui": "D049109", "major_topic": false }, { "descriptor": "Gene Expression Profiling", "descriptor_ui": "D020869", "major_topic": false }, { "descriptor": "Gene Expression Regulation, Neoplastic", "descriptor_ui": "D015972", "major_topic": false }, { "descriptor": "HCT116 Cells", "descriptor_ui": "D045325", "major_topic": false }, { "descriptor": "HEK293 Cells", "descriptor_ui": "D057809", "major_topic": false }, { "descriptor": "Hep G2 Cells", "descriptor_ui": "D056945", "major_topic": false }, { "descriptor": "Histone-Lysine N-Methyltransferase", "descriptor_ui": "D011495", "major_topic": false }, { "descriptor": "Histones", "descriptor_ui": "D006657", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Immunohistochemistry", "descriptor_ui": "D007150", "major_topic": false }, { "descriptor": "Lung Neoplasms", "descriptor_ui": "D008175", "major_topic": false }, { "descriptor": "Methylation", "descriptor_ui": "D008745", "major_topic": false }, { "descriptor": "Neoplasms", "descriptor_ui": "D009369", "major_topic": false }, { "descriptor": "Oligonucleotide Array Sequence Analysis", "descriptor_ui": "D020411", "major_topic": false }, { "descriptor": "Protein Binding", "descriptor_ui": "D011485", "major_topic": false }, { "descriptor": "Repressor Proteins", "descriptor_ui": "D012097", "major_topic": false }, { "descriptor": "Reverse Transcriptase Polymerase Chain Reaction", "descriptor_ui": "D020133", "major_topic": false }, { "descriptor": "RNA Interference", "descriptor_ui": "D034622", "major_topic": false }, { "descriptor": "Tissue Array Analysis", "descriptor_ui": "D046888", "major_topic": false }, { "descriptor": "Urinary Bladder Neoplasms", "descriptor_ui": "D001749", "major_topic": false }, { "descriptor": "Wnt Signaling Pathway", "descriptor_ui": "D060449", "major_topic": true } ], "publication": { "conference_name": null, "date": "2011 Oct", "date_precision": "unknown", "issue": "10", "normalized_date": null, "pages": "887-898", "proceedings_title": null, "publisher": "", "title": "Neoplasia (New York, N.Y.)", "volume": "13", "year": 2011 }, "ssbd": { "database": [], "repository": [] }, "title": "Histone lysine methyltransferase Wolf-Hirschhorn syndrome candidate 1 is involved in human carcinogenesis through regulation of the Wnt pathway.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "OBJECTIVE: The goal of this study was to determine whether inhibition of transient receptor potential canonical (TRPC) channels underlies attenuation of angiotensin II (Ang II)-induced vasoconstriction by phosphodiesterase (PDE) 3 inhibition. METHODS AND RESULTS: Pretreatment of rat thoracic aorta with cilostazol, a selective PDE3 inhibitor, suppressed vasoconstriction induced by Ang II but not that induced by KCl. The Ang II-induced contraction was largely dependent on Ca(2+) influx via receptor-operated cation channels. Cilostazol specifically suppressed diacylglycerol-activated TRPC channels (TRPC3/TRPC6/TRPC7) through protein kinase A (PKA)-dependent phosphorylation of TRPC channels in HEK293 cells. In contrast, we found that phosphorylation of TRPC6 at Thr69 was essential for the suppression of Ang II-induced Ca(2+) influx by PDE3 inhibition in rat aortic smooth muscle cells (RAoSMCs). Cilostazol specifically induced phosphorylation of endogenous TRPC6 at Thr69. The endogenous TRPC6, but not TRPC3, formed a ternary complex with PDE3 and PKA in RAoSMCs, suggesting the specificity of TRPC6 phosphorylation by PDE3 inhibition. Furthermore, inhibition of PDE3 suppressed the Ang II-induced contraction of reconstituted ring with RAoSMCs, which were abolished by the expression of a phosphorylation-deficient mutant of TRPC6. CONCLUSIONS: PKA-mediated phosphorylation of TRPC6 at Thr69 is essential for the vasorelaxant effects of PDE3 inhibition against the vasoconstrictive actions of Ang II.", "classifications": [ { "id": "Nishida", "label": "Group Nishida", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Kinue", "last_name": "Nishioka", "name": null }, { "creator_type": "author", "first_name": "Motohiro", "last_name": "Nishida", "name": null }, { "creator_type": "author", "first_name": "Marina", "last_name": "Ariyoshi", "name": null }, { "creator_type": "author", "first_name": "Zhong", "last_name": "Jian", "name": null }, { "creator_type": "author", "first_name": "Shota", "last_name": "Saiki", "name": null }, { "creator_type": "author", "first_name": "Mayumi", "last_name": "Hirano", "name": null }, { "creator_type": "author", "first_name": "Michio", "last_name": "Nakaya", "name": null }, { "creator_type": "author", "first_name": "Yoji", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Satomi", "last_name": "Kita", "name": null }, { "creator_type": "author", "first_name": "Takahiro", "last_name": "Iwamoto", "name": null }, { "creator_type": "author", "first_name": "Katsuya", "last_name": "Hirano", "name": null }, { "creator_type": "author", "first_name": "Ryuji", "last_name": "Inoue", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Kurose", "name": null } ], "identifiers": { "doi": { "normalized": "10.1161/atvbaha.110.221010" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "21799177" } }, "mesh": [ { "descriptor": "Angiotensin II", "descriptor_ui": "D000804", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Aorta, Thoracic", "descriptor_ui": "D001013", "major_topic": false }, { "descriptor": "Calcium Signaling", "descriptor_ui": "D020013", "major_topic": false }, { "descriptor": "Cilostazol", "descriptor_ui": "D000077407", "major_topic": false }, { "descriptor": "Cyclic AMP-Dependent Protein Kinases", "descriptor_ui": "D017868", "major_topic": false }, { "descriptor": "Diglycerides", "descriptor_ui": "D004075", "major_topic": false }, { "descriptor": "Dose-Response Relationship, Drug", "descriptor_ui": "D004305", "major_topic": false }, { "descriptor": "HEK293 Cells", "descriptor_ui": "D057809", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Muscle, Smooth, Vascular", "descriptor_ui": "D009131", "major_topic": false }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": false }, { "descriptor": "Myocytes, Smooth Muscle", "descriptor_ui": "D032389", "major_topic": false }, { "descriptor": "Phosphodiesterase 3 Inhibitors", "descriptor_ui": "D058987", "major_topic": false }, { "descriptor": "Phosphorylation", "descriptor_ui": "D010766", "major_topic": false }, { "descriptor": "Protein Processing, Post-Translational", "descriptor_ui": "D011499", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Rats, Sprague-Dawley", "descriptor_ui": "D017207", "major_topic": false }, { "descriptor": "rho GTP-Binding Proteins", "descriptor_ui": "D020741", "major_topic": false }, { "descriptor": "Tetrazoles", "descriptor_ui": "D013777", "major_topic": false }, { "descriptor": "Transfection", "descriptor_ui": "D014162", "major_topic": false }, { "descriptor": "TRPC Cation Channels", "descriptor_ui": "D050052", "major_topic": false }, { "descriptor": "TRPC6 Cation Channel", "descriptor_ui": "D000074287", "major_topic": false }, { "descriptor": "Vasoconstriction", "descriptor_ui": "D014661", "major_topic": false }, { "descriptor": "Vasoconstrictor Agents", "descriptor_ui": "D014662", "major_topic": false }, { "descriptor": "Vasodilator Agents", "descriptor_ui": "D014665", "major_topic": false } ], "publication": { "conference_name": null, "date": "2011 Oct", "date_precision": "unknown", "issue": "10", "normalized_date": null, "pages": "2278-2286", "proceedings_title": null, "publisher": "", "title": "Arteriosclerosis, thrombosis, and vascular biology", "volume": "31", "year": 2011 }, "ssbd": { "database": [], "repository": [] }, "title": "Cilostazol suppresses angiotensin II-induced vasoconstriction via protein kinase A-mediated phosphorylation of the transient receptor potential canonical 6 channel.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "MicroRNA (miRNA), non-coding RNA of approximately 22 nucleotides, post-transcriptionally represses expression of its target genes. miRNA regulates a variety of biological processes such as cell proliferation, cell death, development, stemness and genomic stability, not only in physiological conditions but also in various pathological conditions such as cancers. More than 1000 mature miRNA have been experimentally identified in humans and mice, yet the functions of a vast majority of miRNA remain to be elucidated. Identification of novel cancer-associated miRNA seems promising considering their possible application in the development of novel cancer therapies and biomarkers. Currently, there are two major approaches to identify miRNA that are associated with cancer: expression profiling study and functional screening assay. The former approach is widely used, and a large number of studies have shown aberrant miRNA expression profiles in cancer tissues compared with their non-cancer counterparts. Although aberrantly expressed miRNA are potentially good biomarkers, in most cases a majority of them do not play causal roles in cancers when functional assays are performed. In contrast, the latter approach allows screening of 'driver' miRNA with cancer-associated phenotypes, such as cell proliferation and cell invasion. Thus, this approach might be suitable in finding crucial targets of novel cancer therapy. The combination of both types of approaches will contribute to further elucidation of the cancer pathophysiology and to the development of a novel class of cancer therapies and biomarkers.", "classifications": [ { "id": "Okamoto", "label": "Group Okamoto", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Masashi", "last_name": "Izumiya", "name": null }, { "creator_type": "author", "first_name": "Naoto", "last_name": "Tsuchiya", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Okamoto", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Nakagama", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/j.1349-7006.2011.02007.x" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "21668585" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Movement", "descriptor_ui": "D002465", "major_topic": false }, { "descriptor": "Cell Proliferation", "descriptor_ui": "D049109", "major_topic": false }, { "descriptor": "Gene Expression Profiling", "descriptor_ui": "D020869", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "MicroRNAs", "descriptor_ui": "D035683", "major_topic": true }, { "descriptor": "Neoplasms", "descriptor_ui": "D009369", "major_topic": false } ], "publication": { "conference_name": null, "date": "2011 Sep", "date_precision": "unknown", "issue": "9", "normalized_date": null, "pages": "1615-1621", "proceedings_title": null, "publisher": "", "title": "Cancer science", "volume": "102", "year": 2011 }, "ssbd": { "database": [], "repository": [] }, "title": "Systematic exploration of cancer-associated microRNA through functional screening assays.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "INTRODUCTION: Adenocarcinoma is the most common histologic type of lung cancer. To address advances in oncology, molecular biology, pathology, radiology, and surgery of lung adenocarcinoma, an international multidisciplinary classification was sponsored by the International Association for the Study of Lung Cancer, American Thoracic Society, and European Respiratory Society. This new adenocarcinoma classification is needed to provide uniform terminology and diagnostic criteria, especially for bronchioloalveolar carcinoma (BAC), the overall approach to small nonresection cancer specimens, and for multidisciplinary strategic management of tissue for molecular and immunohistochemical studies. METHODS: An international core panel of experts representing all three societies was formed with oncologists/pulmonologists, pathologists, radiologists, molecular biologists, and thoracic surgeons. A systematic review was performed under the guidance of the American Thoracic Society Documents Development and Implementation Committee. The search strategy identified 11,368 citations of which 312 articles met specified eligibility criteria and were retrieved for full text review. A series of meetings were held to discuss the development of the new classification, to develop the recommendations, and to write the current document. Recommendations for key questions were graded by strength and quality of the evidence according to the Grades of Recommendation, Assessment, Development, and Evaluation approach. RESULTS: The classification addresses both resection specimens, and small biopsies and cytology. The terms BAC and mixed subtype adenocarcinoma are no longer used. For resection specimens, new concepts are introduced such as adenocarcinoma in situ (AIS) and minimally invasive adenocarcinoma (MIA) for small solitary adenocarcinomas with either pure lepidic growth (AIS) or predominant lepidic growth with ≤ 5 mm invasion (MIA) to define patients who, if they undergo complete resection, will have 100% or near 100% disease-specific survival, respectively. AIS and MIA are usually nonmucinous but rarely may be mucinous. Invasive adenocarcinomas are classified by predominant pattern after using comprehensive histologic subtyping with lepidic (formerly most mixed subtype tumors with nonmucinous BAC), acinar, papillary, and solid patterns; micropapillary is added as a new histologic subtype. Variants include invasive mucinous adenocarcinoma (formerly mucinous BAC), colloid, fetal, and enteric adenocarcinoma. This classification provides guidance for small biopsies and cytology specimens, as approximately 70% of lung cancers are diagnosed in such samples. Non-small cell lung carcinomas (NSCLCs), in patients with advanced-stage disease, are to be classified into more specific types such as adenocarcinoma or squamous cell carcinoma, whenever possible for several reasons: (1) adenocarcinoma or NSCLC not otherwise specified should be tested for epidermal growth factor receptor (EGFR) mutations as the presence of these mutations is predictive of responsiveness to EGFR tyrosine kinase inhibitors, (2) adenocarcinoma histology is a strong predictor for improved outcome with pemetrexed therapy compared with squamous cell carcinoma, and (3) potential life-threatening hemorrhage may occur in patients with squamous cell carcinoma who receive bevacizumab. If the tumor cannot be classified based on light microscopy alone, special studies such as immunohistochemistry and/or mucin stains should be applied to classify the tumor further. Use of the term NSCLC not otherwise specified should be minimized. CONCLUSIONS: This new classification strategy is based on a multidisciplinary approach to diagnosis of lung adenocarcinoma that incorporates clinical, molecular, radiologic, and surgical issues, but it is primarily based on histology. This classification is intended to support clinical practice, and research investigation and clinical trials. As EGFR mutation is a validated predictive marker for response and progression-free survival with EGFR tyrosine kinase inhibitors in advanced lung adenocarcinoma, we recommend that patients with advanced adenocarcinomas be tested for EGFR mutation. This has implications for strategic management of tissue, particularly for small biopsies and cytology samples, to maximize high-quality tissue available for molecular studies. Potential impact for tumor, node, and metastasis staging include adjustment of the size T factor according to only the invasive component (1) pathologically in invasive tumors with lepidic areas or (2) radiologically by measuring the solid component of part-solid nodules.", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "William D.", "last_name": "Travis", "name": null }, { "creator_type": "author", "first_name": "Elisabeth", "last_name": "Brambilla", "name": null }, { "creator_type": "author", "first_name": "Masayuki", "last_name": "Noguchi", "name": null }, { "creator_type": "author", "first_name": "Andrew G.", "last_name": "Nicholson", "name": null }, { "creator_type": "author", "first_name": "Kim R.", "last_name": "Geisinger", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null }, { "creator_type": "author", "first_name": "David G.", "last_name": "Beer", "name": null }, { "creator_type": "author", "first_name": "Charles A.", "last_name": "Powell", "name": null }, { "creator_type": "author", "first_name": "Gregory J.", "last_name": "Riely", "name": null }, { "creator_type": "author", "first_name": "Paul E.", "last_name": "Van Schil", "name": null }, { "creator_type": "author", "first_name": "Kavita", "last_name": "Garg", "name": null }, { "creator_type": "author", "first_name": "John H. M.", "last_name": "Austin", "name": null }, { "creator_type": "author", "first_name": "Hisao", "last_name": "Asamura", "name": null }, { "creator_type": "author", "first_name": "Valerie W.", "last_name": "Rusch", "name": null }, { "creator_type": "author", "first_name": "Fred R.", "last_name": "Hirsch", "name": null }, { "creator_type": "author", "first_name": "Giorgio", "last_name": "Scagliotti", "name": null }, { "creator_type": "author", "first_name": "Tetsuya", "last_name": "Mitsudomi", "name": null }, { "creator_type": "author", "first_name": "Rudolf M.", "last_name": "Huber", "name": null }, { "creator_type": "author", "first_name": "Yuichi", "last_name": "Ishikawa", "name": null }, { "creator_type": "author", "first_name": "James", "last_name": "Jett", "name": null }, { "creator_type": "author", "first_name": "Montserrat", "last_name": "Sanchez-Cespedes", "name": null }, { "creator_type": "author", "first_name": "Jean-Paul", "last_name": "Sculier", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Tsuboi", "name": null }, { "creator_type": "author", "first_name": "Johan", "last_name": "Vansteenkiste", "name": null }, { "creator_type": "author", "first_name": "Ignacio", "last_name": "Wistuba", "name": null }, { "creator_type": "author", "first_name": "Pan-Chyr", "last_name": "Yang", "name": null }, { "creator_type": "author", "first_name": "Denise", "last_name": "Aberle", "name": null }, { "creator_type": "author", "first_name": "Christian", "last_name": "Brambilla", "name": null }, { "creator_type": "author", "first_name": "Douglas", "last_name": "Flieder", "name": null }, { "creator_type": "author", "first_name": "Wilbur", "last_name": "Franklin", "name": null }, { "creator_type": "author", "first_name": "Adi", "last_name": "Gazdar", "name": null }, { "creator_type": "author", "first_name": "Michael", "last_name": "Gould", "name": null }, { "creator_type": "author", "first_name": "Philip", "last_name": "Hasleton", "name": null }, { "creator_type": "author", "first_name": "Douglas", "last_name": "Henderson", "name": null }, { "creator_type": "author", "first_name": "Bruce", "last_name": "Johnson", "name": null }, { "creator_type": "author", "first_name": "David", "last_name": "Johnson", "name": null }, { "creator_type": "author", "first_name": "Keith", "last_name": "Kerr", "name": null }, { "creator_type": "author", "first_name": "Keiko", "last_name": "Kuriyama", "name": null }, { "creator_type": "author", "first_name": "Jin Soo", "last_name": "Lee", "name": null }, { "creator_type": "author", "first_name": "Vincent A.", "last_name": "Miller", "name": null }, { "creator_type": "author", "first_name": "Iver", "last_name": "Petersen", "name": null }, { "creator_type": "author", "first_name": "Victor", "last_name": "Roggli", "name": null }, { "creator_type": "author", "first_name": "Rafael", "last_name": "Rosell", "name": null }, { "creator_type": "author", "first_name": "Nagahiro", "last_name": "Saijo", "name": null }, { "creator_type": "author", "first_name": "Erik", "last_name": "Thunnissen", "name": null }, { "creator_type": "author", "first_name": "Ming", "last_name": "Tsao", "name": null }, { "creator_type": "author", "first_name": "David", "last_name": "Yankelevitz", "name": null } ], "identifiers": { "doi": { "normalized": "10.1097/jto.0b013e318206a221" }, "pmcid": { "normalized": "PMC4513953" }, "pmid": { "normalized": "21252716" } }, "mesh": [ { "descriptor": "Adenocarcinoma", "descriptor_ui": "D000230", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Lung Neoplasms", "descriptor_ui": "D008175", "major_topic": false }, { "descriptor": "Neoplasm Staging", "descriptor_ui": "D009367", "major_topic": false }, { "descriptor": "Societies, Medical", "descriptor_ui": "D012955", "major_topic": false } ], "publication": { "conference_name": null, "date": "2011 Feb", "date_precision": "unknown", "issue": "2", "normalized_date": null, "pages": "244-285", "proceedings_title": null, "publisher": "", "title": "Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer", "volume": "6", "year": 2011 }, "ssbd": { "database": [], "repository": [] }, "title": "International association for the study of lung cancer/american thoracic society/european respiratory society international multidisciplinary classification of lung adenocarcinoma.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Intercellular surface tension is a key variable in understanding cellular mechanics. However, conventional methods are not well suited for measuring the absolute magnitude of intercellular surface tension because these methods require determination of the effective viscosity of the whole cell, a quantity that is difficult to measure. In this study, we present a novel method for estimating the intercellular surface tension at single-cell resolution. This method exploits the cytoplasmic flow that accompanies laser-induced cell fusion when the pressure difference between cells is large. Because the cytoplasmic viscosity can be measured using well-established technology, this method can be used to estimate the absolute magnitudes of tension. We applied this method to two-cell-stage embryos of the nematode Caenorhabditis elegans and estimated the intercellular surface tension to be in the 30-90 microN m(-1) range. Our estimate was in close agreement with cell-medium surface tensions measured at single-cell resolution.", "classifications": [ { "id": "Onami", "label": "Group Onami", "parent": "Fujiwara", "type": "group" }, { "id": "Fujiwara", "label": "Team Fujiwara", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Masashi", "last_name": "Fujita", "name": null }, { "creator_type": "author", "first_name": "Shuichi", "last_name": "Onami", "name": null } ], "identifiers": { "doi": { "normalized": "10.1088/1478-3975/8/6/064001" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "22146596" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Caenorhabditis elegans", "descriptor_ui": "D017173", "major_topic": false }, { "descriptor": "Cell Fusion", "descriptor_ui": "D002459", "major_topic": false }, { "descriptor": "Cytoplasm", "descriptor_ui": "D003593", "major_topic": false }, { "descriptor": "Lasers", "descriptor_ui": "D007834", "major_topic": true }, { "descriptor": "Surface Tension", "descriptor_ui": "D013500", "major_topic": false }, { "descriptor": "Viscosity", "descriptor_ui": "D014783", "major_topic": false } ], "publication": { "conference_name": null, "date": "2011 Dec", "date_precision": "unknown", "issue": "6", "normalized_date": null, "pages": "064001", "proceedings_title": null, "publisher": "", "title": "Physical biology", "volume": "8", "year": 2011 }, "ssbd": { "database": [], "repository": [] }, "title": "Estimating intercellular surface tension by laser-induced cell fusion.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "In metazoans, geminin functions as a molecular switch for preventing re-replication of chromosomal DNA. Geminin binds to and inhibits Cdt1, which is required for replication origin licensing, but little is known about the mechanisms underlying geminin's all-or-none action in licensing inhibition. Using Xenopus egg extract, we found that the all-or-none activity correlated with the formation of Cdt1 foci on chromatin, suggesting that multiple Cdt1-geminin complexes on origins cooperatively inhibit licensing. Based on experimental identification of licensing intermediates targeted by geminin and Cdt1, we developed a mathematical model of the licensing process. The model involves positive feedback owing to the cooperative action of geminin at neighboring origins and accurately accounts for the licensing activity mediated by geminin and Cdt1 in the extracts. The model also predicts that such cooperativity leads to clustering of licensing-inhibited origins, an idea that is supported by the experimentally measured distribution of inter-origin distances. We propose that geminin inhibits licensing through an inter-origin interaction, ensuring strict and coordinated control of multiple replication origins on chromosomes.", "classifications": [ { "id": "Fujimoto", "label": "Group Fujimoto", "parent": "Ueda", "type": "group" }, { "id": "Ueda", "label": "Team Ueda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Koji L.", "last_name": "Ode", "name": null }, { "creator_type": "author", "first_name": "Koichi", "last_name": "Fujimoto", "name": null }, { "creator_type": "author", "first_name": "Yumiko", "last_name": "Kubota", "name": null }, { "creator_type": "author", "first_name": "Haruhiko", "last_name": "Takisawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/j.1365-2443.2011.01501.x" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "21426446" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Cycle Proteins", "descriptor_ui": "D018797", "major_topic": false }, { "descriptor": "Chromatin", "descriptor_ui": "D002843", "major_topic": false }, { "descriptor": "DNA Replication", "descriptor_ui": "D004261", "major_topic": false }, { "descriptor": "DNA-Binding Proteins", "descriptor_ui": "D004268", "major_topic": false }, { "descriptor": "Geminin", "descriptor_ui": "D064248", "major_topic": false }, { "descriptor": "Models, Biological", "descriptor_ui": "D008954", "major_topic": false }, { "descriptor": "Replication Origin", "descriptor_ui": "D018741", "major_topic": false }, { "descriptor": "Xenopus", "descriptor_ui": "D014981", "major_topic": false }, { "descriptor": "Xenopus Proteins", "descriptor_ui": "D029867", "major_topic": false } ], "publication": { "conference_name": null, "date": "2011 Apr", "date_precision": "unknown", "issue": "4", "normalized_date": null, "pages": "380-396", "proceedings_title": null, "publisher": "", "title": "Genes to cells : devoted to molecular & cellular mechanisms", "volume": "16", "year": 2011 }, "ssbd": { "database": [], "repository": [] }, "title": "Inter-origin cooperativity of geminin action establishes an all-or-none switch for replication origin licensing.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Similar to the adenoma-carcinoma sequence of colorectal cancer, lung adenocarcinoma is thought to follow a linear multistep progression, in which a precursor lesion progresses to adenocarcinoma in situ, which is followed by invasive adenocarcinoma. However, lung adenocarcinoma can no longer be considered as a single type of tumor but rather a group of distinct subsets of tumors that arise from different molecular pathways. Consistent with this concept, recent findings revealed that this linear progression might not occur in all lung adenocarcinomas. First, according to the molecular classification based on expression profiling, lung cancer can be divided into at least two subsets; precancerous and in situ lesions share characteristics of molecular expression and clinical features with only one of the two subsets, suggesting that the linear progression is only applicable to the subset in the molecular classification. Second, when EGFR and KRAS were examined based on the progression steps, the mutation rate of KRAS was disproportionally distributed; however, according to the progression schema, gene alterations should be evenly accumulated along the entire progression. Third, by means of comparative genomic hybridization analysis, some adenocarcinoma in situ revealed gene alterations discontinuous to invasive adenocarcinoma. Finally, there were some clinical observations that support that some lesions escape from the progression. In this review, we hypothesize a novel scenario for the progression of lung adenocarcinoma, which does not support a linear progression schema.", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null }, { "creator_type": "author", "first_name": "Alain C.", "last_name": "Borczuk", "name": null }, { "creator_type": "author", "first_name": "Charles A.", "last_name": "Powell", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.lungcan.2011.05.021" }, "pmcid": { "normalized": "PMC3172366" }, "pmid": { "normalized": "21705107" } }, "mesh": [ { "descriptor": "Adenocarcinoma", "descriptor_ui": "D000230", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Transformation, Neoplastic", "descriptor_ui": "D002471", "major_topic": true }, { "descriptor": "Cellular Senescence", "descriptor_ui": "D016922", "major_topic": false }, { "descriptor": "Disease Progression", "descriptor_ui": "D018450", "major_topic": false }, { "descriptor": "ErbB Receptors", "descriptor_ui": "D066246", "major_topic": false }, { "descriptor": "Gene Expression Profiling", "descriptor_ui": "D020869", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Lung Neoplasms", "descriptor_ui": "D008175", "major_topic": false }, { "descriptor": "Models, Biological", "descriptor_ui": "D008954", "major_topic": true }, { "descriptor": "Mutation Rate", "descriptor_ui": "D059645", "major_topic": false }, { "descriptor": "Neoplasm Invasiveness", "descriptor_ui": "D009361", "major_topic": false }, { "descriptor": "Neoplastic Stem Cells", "descriptor_ui": "D014411", "major_topic": false }, { "descriptor": "Precancerous Conditions", "descriptor_ui": "D011230", "major_topic": false }, { "descriptor": "Proto-Oncogene Proteins", "descriptor_ui": "D011518", "major_topic": false }, { "descriptor": "Proto-Oncogene Proteins p21(ras)", "descriptor_ui": "D016283", "major_topic": false }, { "descriptor": "ras Proteins", "descriptor_ui": "D018631", "major_topic": false } ], "publication": { "conference_name": null, "date": "2011 Oct", "date_precision": "unknown", "issue": "1", "normalized_date": null, "pages": "7-11", "proceedings_title": null, "publisher": "", "title": "Lung cancer (Amsterdam, Netherlands)", "volume": "74", "year": 2011 }, "ssbd": { "database": [], "repository": [] }, "title": "Do all lung adenocarcinomas follow a stepwise progression?", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Chronic hepatitis C virus (HCV) infection is often associated with type 2 diabetes. However, the precise mechanism underlying this association is still unclear. Here, using Huh-7.5 cells either harboring HCV-1b RNA replicons or infected with HCV-2a, we showed that HCV transcriptionally upregulated the genes for phosphoenolpyruvate carboxykinase (PEPCK) and glucose 6-phosphatase (G6Pase), the rate-limiting enzymes for hepatic gluconeogenesis. In this way, HCV enhanced the cellular production of glucose 6-phosphate (G6P) and glucose. PEPCK and G6Pase gene expressions are controlled by the transcription factor forkhead box O1 (FoxO1). We observed that although neither the mRNA levels nor the protein levels of FoxO1 expression were affected by HCV, the level of phosphorylation of FoxO1 at Ser319 was markedly diminished in HCV-infected cells compared to the control cells, resulting in an increased nuclear accumulation of FoxO1, which is essential for sustaining its transcriptional activity. It was unlikely that the decreased level of FoxO1 phosphorylation was mediated through Akt inactivation, as we observed an increased phosphorylation of Akt at Ser473 in HCV-infected cells compared to control cells. By using specific inhibitors of c-Jun N-terminal kinase (JNK) and reactive oxygen species (ROS), we demonstrated that HCV infection induced JNK activation via increased mitochondrial ROS production, resulting in decreased FoxO1 phosphorylation, FoxO1 nuclear accumulation, and, eventually, increased glucose production. We also found that HCV NS5A mediated increased ROS production and JNK activation, which is directly linked with the FoxO1-dependent increased gluconeogenesis. Taken together, these observations suggest that HCV promotes hepatic gluconeogenesis through an NS5A-mediated, FoxO1-dependent pathway.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Lin", "last_name": "Deng", "name": null }, { "creator_type": "author", "first_name": "Ikuo", "last_name": "Shoji", "name": null }, { "creator_type": "author", "first_name": "Wataru", "last_name": "Ogawa", "name": null }, { "creator_type": "author", "first_name": "Shusaku", "last_name": "Kaneda", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Da-peng", "last_name": "Jiang", "name": null }, { "creator_type": "author", "first_name": "Yoshi-Hiro", "last_name": "Ide", "name": null }, { "creator_type": "author", "first_name": "Hak", "last_name": "Hotta", "name": null } ], "identifiers": { "doi": { "normalized": "10.1128/jvi.00146-11" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "21697492" } }, "mesh": [ { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "Cell Nucleus", "descriptor_ui": "D002467", "major_topic": false }, { "descriptor": "Forkhead Box Protein O1", "descriptor_ui": "D000071161", "major_topic": false }, { "descriptor": "Forkhead Transcription Factors", "descriptor_ui": "D051858", "major_topic": false }, { "descriptor": "Gene Expression Profiling", "descriptor_ui": "D020869", "major_topic": false }, { "descriptor": "Gluconeogenesis", "descriptor_ui": "D005943", "major_topic": true }, { "descriptor": "Glucose", "descriptor_ui": "D005947", "major_topic": false }, { "descriptor": "Glucose-6-Phosphate", "descriptor_ui": "D019298", "major_topic": false }, { "descriptor": "Hepacivirus", "descriptor_ui": "D016174", "major_topic": false }, { "descriptor": "Hepatocytes", "descriptor_ui": "D022781", "major_topic": false }, { "descriptor": "Host-Pathogen Interactions", "descriptor_ui": "D054884", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Phosphorylation", "descriptor_ui": "D010766", "major_topic": false }, { "descriptor": "Protein Interaction Mapping", "descriptor_ui": "D025941", "major_topic": false }, { "descriptor": "RNA-Dependent RNA Polymerase", "descriptor_ui": "D012324", "major_topic": false }, { "descriptor": "Viral Nonstructural Proteins", "descriptor_ui": "D017361", "major_topic": false } ], "publication": { "conference_name": null, "date": "2011 Sep", "date_precision": "unknown", "issue": "17", "normalized_date": null, "pages": "8556-8568", "proceedings_title": null, "publisher": "", "title": "Journal of Virology", "volume": "85", "year": 2011 }, "ssbd": { "database": [], "repository": [] }, "title": "Hepatitis C Virus Infection Promotes Hepatic Gluconeogenesis through an NS5A-Mediated, FoxO1-Dependent Pathway▿.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Cell chemotaxis has been characterized as the formation of a front-back axis that is triggered by a gradient of chemoattractant; however, chemotaxis is accompanied by more complicated behaviors. These include migration in a straight line with a stable axis [the stable single-axis (SSA) pattern] and repeated splitting of the leading edge of the cell into two regions, followed by the \"choice\" of one of these as the new leading edge [the split and choice (S&C) pattern]. Indeed, transition between these two behaviors can be observed in individual cells. However, the conceptual framework of the network of signaling molecules that generates these patterns remains to be clarified. We confirmed theoretically that a system that has positive and negative feedback loops involving the reciprocal cycling between the membrane and the cytosol of molecules that promote membrane protrusion or retraction generates SSA and S&C patterns of migratory behavior under similar conditions. We also predicted properties of the instabilities of such a system, which are essential for the generation of these behaviors, and we verified their existence in chemotaxing cells. Our research provides a simple model of network structure for chemotactic behaviors, including cell polarization.", "classifications": [ { "id": "Ishihara", "label": "Group Ishihara", "parent": "Sawai", "type": "group" }, { "id": "Kuroda", "label": "Group Kuroda", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" }, { "id": "Sawai", "label": "Team Sawai", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Mikiya", "last_name": "Otsuji", "name": null }, { "creator_type": "author", "first_name": "Yuya", "last_name": "Terashima", "name": null }, { "creator_type": "author", "first_name": "Shuji", "last_name": "Ishihara", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Kuroda", "name": null }, { "creator_type": "author", "first_name": "Kouji", "last_name": "Matsushima", "name": null } ], "identifiers": { "doi": { "normalized": "10.1126/scisignal.2001056" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "21156936" } }, "mesh": [ { "descriptor": "Biological Transport", "descriptor_ui": "D001692", "major_topic": false }, { "descriptor": "Cell Membrane", "descriptor_ui": "D002462", "major_topic": false }, { "descriptor": "Cell Polarity", "descriptor_ui": "D016764", "major_topic": false }, { "descriptor": "Chemotaxis", "descriptor_ui": "D002633", "major_topic": true }, { "descriptor": "Cytosol", "descriptor_ui": "D003600", "major_topic": false }, { "descriptor": "Feedback, Physiological", "descriptor_ui": "D025461", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false } ], "publication": { "conference_name": null, "date": "2010 Dec 14", "date_precision": "day", "issue": "152", "normalized_date": "2010-12-14", "pages": "ra89", "proceedings_title": null, "publisher": "", "title": "Science signaling", "volume": "3", "year": 2010 }, "ssbd": { "database": [], "repository": [] }, "title": "A conceptual molecular network for chemotactic behaviors characterized by feedback of molecules cycling between the membrane and the cytosol.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "l-Cysteine is ubiquitous in all living organisms and is involved in a variety of functions, including the synthesis of iron-sulfur clusters and glutathione and the regulation of the structure, stability, and catalysis of proteins. In the protozoan parasite Entamoeba histolytica, the causative agent of amebiasis, l-cysteine plays an essential role in proliferation, adherence, and defense against oxidative stress; however, the essentiality of this amino acid in the pathways it regulates is not well understood. In the present study, we applied capillary electrophoresis time-of-flight mass spectrometry to quantitate charged metabolites modulated in response to l-cysteine deprivation in E. histolytica, which was selected as a model for examining the biological roles of l-cysteine. l-Cysteine deprivation had profound effects on glycolysis, amino acid, and phospholipid metabolism, with sharp decreases in the levels of l-cysteine, l-cystine, and S-adenosylmethionine and a dramatic accumulation of O-acetylserine and S-methylcysteine. We further demonstrated that S-methylcysteine is synthesized from methanethiol and O-acetylserine by cysteine synthase, which was previously considered to be involved in sulfur-assimilatory l-cysteine biosynthesis. In addition, l-cysteine depletion repressed glycolysis and energy generation, as it reduced acetyl-CoA, ethanol, and the major nucleotide di- and triphosphates, and led to the accumulation of glycolytic intermediates. Interestingly, l-cysteine depletion increased the synthesis of isopropanolamine and phosphatidylisopropanolamine, and it was confirmed that their increment was not a result of oxidative stress but was a specific response to l-cysteine depletion. We also identified a pathway in which isopropanolamine is synthesized from methylglyoxal via aminoacetone. To date, this study represents the first case where l-cysteine deprivation leads to drastic changes in core metabolic pathways, including energy, amino acid, and phospholipid metabolism.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Afzal", "last_name": "Husain", "name": null }, { "creator_type": "author", "first_name": "Dan", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Ghulam", "last_name": "Jeelani", "name": null }, { "creator_type": "author", "first_name": "Fumika", "last_name": "Mi-ichi", "name": null }, { "creator_type": "author", "first_name": "Vahab", "last_name": "Ali", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Suematsu", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Nozaki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1074/jbc.m110.167304" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "20923776" } }, "mesh": [ { "descriptor": "Chromatography, Thin Layer", "descriptor_ui": "D002855", "major_topic": false }, { "descriptor": "Cysteine", "descriptor_ui": "D003545", "major_topic": false }, { "descriptor": "Cysteine Synthase", "descriptor_ui": "D003547", "major_topic": false }, { "descriptor": "Entamoeba histolytica", "descriptor_ui": "D004748", "major_topic": false }, { "descriptor": "Gene Expression Regulation", "descriptor_ui": "D005786", "major_topic": false }, { "descriptor": "Glycolysis", "descriptor_ui": "D006019", "major_topic": false }, { "descriptor": "Kinetics", "descriptor_ui": "D007700", "major_topic": false }, { "descriptor": "Metabolomics", "descriptor_ui": "D055432", "major_topic": false }, { "descriptor": "Oxidative Stress", "descriptor_ui": "D018384", "major_topic": false }, { "descriptor": "Propanolamines", "descriptor_ui": "D011412", "major_topic": false }, { "descriptor": "S-Adenosylmethionine", "descriptor_ui": "D012436", "major_topic": false }, { "descriptor": "Serine", "descriptor_ui": "D012694", "major_topic": false } ], "publication": { "conference_name": null, "date": "2010 Dec 10", "date_precision": "day", "issue": "50", "normalized_date": "2010-12-10", "pages": "39160-39170", "proceedings_title": null, "publisher": "", "title": "The Journal of Biological Chemistry", "volume": "285", "year": 2010 }, "ssbd": { "database": [], "repository": [] }, "title": "Metabolome Analysis Revealed Increase in S-Methylcysteine and Phosphatidylisopropanolamine Synthesis upon l-Cysteine Deprivation in the Anaerobic Protozoan Parasite Entamoeba histolytica*.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Molecular events in biological cells occur in local subregions, where the molecules tend to be small in number. The cytoskeleton, which is important for both the structural changes of cells and their functions, is also a countable entity because of its long fibrous shape. To simulate the local environment using a computer, stochastic simulations should be run. We herein report a new method of stochastic simulation based on random walk and reaction by the collision of all molecules. The microscopic reaction rate P(r) is calculated from the macroscopic rate constant k. The formula involves only local parameters embedded for each molecule. The results of the stochastic simulations of simple second-order, polymerization, Michaelis-Menten-type and other reactions agreed quite well with those of deterministic simulations when the number of molecules was sufficiently large. An analysis of the theory indicated a relationship between variance and the number of molecules in the system, and results of multiple stochastic simulation runs confirmed this relationship. We simulated Ca(2)(+) dynamics in a cell by inward flow from a point on the cell surface and the polymerization of G-actin forming F-actin. Our results showed that this theory and method can be used to simulate spatially inhomogeneous events.", "classifications": [ { "id": "Suzuki", "label": "Group Suzuki", "parent": "Takekawa", "type": "group" }, { "id": "Takekawa", "label": "Team Takekawa", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Kazuhisa", "last_name": "Ichikawa", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Noboru", "last_name": "Murata", "name": null } ], "identifiers": { "doi": { "normalized": "10.1088/1478-3975/7/4/046010" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "21119218" } }, "mesh": [ { "descriptor": "Actins", "descriptor_ui": "D000199", "major_topic": false }, { "descriptor": "Algorithms", "descriptor_ui": "D000465", "major_topic": false }, { "descriptor": "Biopolymers", "descriptor_ui": "D001704", "major_topic": false }, { "descriptor": "Kinetics", "descriptor_ui": "D007700", "major_topic": false }, { "descriptor": "Models, Theoretical", "descriptor_ui": "D008962", "major_topic": true }, { "descriptor": "Stochastic Processes", "descriptor_ui": "D013269", "major_topic": true } ], "publication": { "conference_name": null, "date": "2010 Nov 30", "date_precision": "day", "issue": "4", "normalized_date": "2010-11-30", "pages": "046010", "proceedings_title": null, "publisher": "", "title": "Physical biology", "volume": "7", "year": 2010 }, "ssbd": { "database": [], "repository": [] }, "title": "Stochastic simulation of biological reactions, and its applications for studying actin polymerization.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Transposons are mobile DNA segments that can disrupt gene function by inserting in or near genes. Here, we show that insertional mutagenesis by the PiggyBac transposon can be used for cancer gene discovery in mice. PiggyBac transposition in genetically engineered transposon-transposase mice induced cancers whose type (hematopoietic versus solid) and latency were dependent on the regulatory elements introduced into transposons. Analysis of 63 hematopoietic tumors revealed that PiggyBac is capable of genome-wide mutagenesis. The PiggyBac screen uncovered many cancer genes not identified in previous retroviral or Sleeping Beauty transposon screens, including Spic, which encodes a PU.1-related transcription factor, and Hdac7, a histone deacetylase gene. PiggyBac and Sleeping Beauty have different integration preferences. To maximize the utility of the tool, we engineered 21 mouse lines to be compatible with both transposon systems in constitutive, tissue- or temporal-specific mutagenesis. Mice with different transposon types, copy numbers, and chromosomal locations support wide applicability.", "classifications": [ { "id": "Yusa", "label": "Group Yusa", "parent": "Eiraku", "type": "group" }, { "id": "Eiraku", "label": "Team Eiraku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Roland", "last_name": "Rad", "name": null }, { "creator_type": "author", "first_name": "Lena", "last_name": "Rad", "name": null }, { "creator_type": "author", "first_name": "Wei", "last_name": "Wang", "name": null }, { "creator_type": "author", "first_name": "Juan", "last_name": "Cadinanos", "name": null }, { "creator_type": "author", "first_name": "George", "last_name": "Vassiliou", "name": null }, { "creator_type": "author", "first_name": "Stephen", "last_name": "Rice", "name": null }, { "creator_type": "author", "first_name": "Lia S.", "last_name": "Campos", "name": null }, { "creator_type": "author", "first_name": "Kosuke", "last_name": "Yusa", "name": null }, { "creator_type": "author", "first_name": "Ruby", "last_name": "Banerjee", "name": null }, { "creator_type": "author", "first_name": "Meng Amy", "last_name": "Li", "name": null }, { "creator_type": "author", "first_name": "Jorge", "last_name": "de la Rosa", "name": null }, { "creator_type": "author", "first_name": "Alexander", "last_name": "Strong", "name": null }, { "creator_type": "author", "first_name": "Dong", "last_name": "Lu", "name": null }, { "creator_type": "author", "first_name": "Peter", "last_name": "Ellis", "name": null }, { "creator_type": "author", "first_name": "Nathalie", "last_name": "Conte", "name": null }, { "creator_type": "author", "first_name": "Fang Tang", "last_name": "Yang", "name": null }, { "creator_type": "author", "first_name": "Pentao", "last_name": "Liu", "name": null }, { "creator_type": "author", "first_name": "Allan", "last_name": "Bradley", "name": null } ], "identifiers": { "doi": { "normalized": "10.1126/science.1193004" }, "pmcid": { "normalized": "PMC3719098" }, "pmid": { "normalized": "20947725" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "DNA Transposable Elements", "descriptor_ui": "D004251", "major_topic": true }, { "descriptor": "Genes, Neoplasm", "descriptor_ui": "D052138", "major_topic": true }, { "descriptor": "Genetic Testing", "descriptor_ui": "D005820", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Transgenic", "descriptor_ui": "D008822", "major_topic": false }, { "descriptor": "Mutagenesis, Insertional", "descriptor_ui": "D016254", "major_topic": true }, { "descriptor": "Neoplasms", "descriptor_ui": "D009369", "major_topic": false }, { "descriptor": "Oncogenes", "descriptor_ui": "D009857", "major_topic": false }, { "descriptor": "Promoter Regions, Genetic", "descriptor_ui": "D011401", "major_topic": false } ], "publication": { "conference_name": null, "date": "2010 Nov 19", "date_precision": "day", "issue": "6007", "normalized_date": "2010-11-19", "pages": "1104-1107", "proceedings_title": null, "publisher": "", "title": "Science (New York, N.Y.)", "volume": "330", "year": 2010 }, "ssbd": { "database": [], "repository": [] }, "title": "PiggyBac transposon mutagenesis: a tool for cancer gene discovery in mice.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: Macrophages represent the front lines of our immune system; they recognize and engulf pathogens or foreign particles thus initiating the immune response. Imaging macrophages presents unique challenges, as most optical techniques require labeling or staining of the cellular compartments in order to resolve organelles, and such stains or labels have the potential to perturb the cell, particularly in cases where incomplete information exists regarding the precise cellular reaction under observation. Label-free imaging techniques such as Raman microscopy are thus valuable tools for studying the transformations that occur in immune cells upon activation, both on the molecular and organelle levels. Due to extremely low signal levels, however, Raman microscopy requires sophisticated image processing techniques for noise reduction and signal extraction. To date, efficient, automated algorithms for resolving sub-cellular features in noisy, multi-dimensional image sets have not been explored extensively. RESULTS: We show that hybrid z-score normalization and standard regression (Z-LSR) can highlight the spectral differences within the cell and provide image contrast dependent on spectral content. In contrast to typical Raman imaging processing methods using multivariate analysis, such as single value decomposition (SVD), our implementation of the Z-LSR method can operate nearly in real-time. In spite of its computational simplicity, Z-LSR can automatically remove background and bias in the signal, improve the resolution of spatially distributed spectral differences and enable sub-cellular features to be resolved in Raman microscopy images of mouse macrophage cells. Significantly, the Z-LSR processed images automatically exhibited subcellular architectures whereas SVD, in general, requires human assistance in selecting the components of interest. CONCLUSIONS: The computational efficiency of Z-LSR enables automated resolution of sub-cellular features in large Raman microscopy data sets without compromise in image quality or information loss in associated spectra. These results motivate further use of label free microscopy techniques in real-time imaging of live immune cells.", "classifications": [ { "id": "Fujita", "label": "Group Fujita", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Robert J.", "last_name": "Milewski", "name": null }, { "creator_type": "author", "first_name": "Yutaro", "last_name": "Kumagai", "name": null }, { "creator_type": "author", "first_name": "Katsumasa", "last_name": "Fujita", "name": null }, { "creator_type": "author", "first_name": "Daron M.", "last_name": "Standley", "name": null }, { "creator_type": "author", "first_name": "Nicholas I.", "last_name": "Smith", "name": null } ], "identifiers": { "doi": { "normalized": "10.1186/1745-7580-6-11" }, "pmcid": { "normalized": "PMC2995782" }, "pmid": { "normalized": "21092116" } }, "mesh": [], "publication": { "conference_name": null, "date": "2010 Nov 19", "date_precision": "day", "issue": "", "normalized_date": "2010-11-19", "pages": "11", "proceedings_title": null, "publisher": "", "title": "Immunome research", "volume": "6", "year": 2010 }, "ssbd": { "database": [], "repository": [] }, "title": "Automated processing of label-free Raman microscope images of macrophage cells with standardized regression for high-throughput analysis.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The actin cytoskeleton undergoes rapid changes in its architecture during mitosis. Here, we demonstrate novel actin assembly dynamics in M phase. An amorphous cluster of actin filaments appears during prometaphase, revolves horizontally along the cell cortex at a constant angular speed, and fuses into the contractile ring after three to four revolutions. Cdk1 activity is required for the formation of this mitotic actin cluster and its revolving movement. Rapid turnover of actin in the filaments takes place everywhere in the cluster and is also required for its cluster rotation during mitosis. Knockdown of Arp3, a component of the actin filament-nucleating Arp2/3 complex, inhibits the formation of the mitotic actin cluster without affecting other actin structures. These results identify Arp2/3 complex as a key factor in the generation of the dynamic actin cluster during mitosis.", "classifications": [ { "id": "Toyoshima", "label": "Group Toyoshima", "parent": "Toyoshima", "type": "group" }, { "id": "Yamamoto", "label": "Group Yamamoto", "parent": "Toyoshima", "type": "group" }, { "id": "Toyoshima", "label": "Team Toyoshima", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Masaru", "last_name": "Mitsushima", "name": null }, { "creator_type": "author", "first_name": "Kazuhiro", "last_name": "Aoki", "name": null }, { "creator_type": "author", "first_name": "Miki", "last_name": "Ebisuya", "name": null }, { "creator_type": "author", "first_name": "Shigeru", "last_name": "Matsumura", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Michiyuki", "last_name": "Matsuda", "name": null }, { "creator_type": "author", "first_name": "Fumiko", "last_name": "Toyoshima", "name": null }, { "creator_type": "author", "first_name": "Eisuke", "last_name": "Nishida", "name": null } ], "identifiers": { "doi": { "normalized": "10.1083/jcb.201007136" }, "pmcid": { "normalized": "PMC3003322" }, "pmid": { "normalized": "20974812" } }, "mesh": [ { "descriptor": "Actin Cytoskeleton", "descriptor_ui": "D008841", "major_topic": false }, { "descriptor": "Actin-Related Protein 2-3 Complex", "descriptor_ui": "D051376", "major_topic": false }, { "descriptor": "Actins", "descriptor_ui": "D000199", "major_topic": false }, { "descriptor": "CDC2 Protein Kinase", "descriptor_ui": "D016203", "major_topic": false }, { "descriptor": "Cell Division", "descriptor_ui": "D002455", "major_topic": false }, { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "Cytoskeleton", "descriptor_ui": "D003599", "major_topic": false }, { "descriptor": "HeLa Cells", "descriptor_ui": "D006367", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mitosis", "descriptor_ui": "D008938", "major_topic": true } ], "publication": { "conference_name": null, "date": "2010 Nov 1", "date_precision": "day", "issue": "3", "normalized_date": "2010-11-01", "pages": "453-462", "proceedings_title": null, "publisher": "", "title": "The Journal of cell biology", "volume": "191", "year": 2010 }, "ssbd": { "database": [], "repository": [] }, "title": "Revolving movement of a dynamic cluster of actin filaments during mitosis.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "We performed this study to understand the anatomical substrates of parabrachial nucleus (PBN) modulation of orexin (ORX)-containing neurons in the hypothalamus. After biotinylated dextranamine (BDA) injection into the lateral PBN and immunostaining of ORX-containing neurons in the rat, the prominent overlap of the distribution field of the BDA-labeled fibers and that of the ORX-immunoreactive (ir) neurons was found in the lateralmost part of the dorsomedial nucleus and adjacent dorsal perifornical area (this overlapping field was referred to as \"suprafornical area\" in the present study), and the labeled axon terminals made asymmetrical synaptic contacts with somata and dendrites of the ORX-ir neurons. We further revealed that almost all the \"suprafornical area\"-projecting lateral PBN neurons were positive for vesicular glutamate transporter 2 mRNA and very few of them were positive for glutamic acid decarboxylase 67 mRNA. The present data suggest that ORX-containing neurons in the \"suprafornical area\" may be under the excitatory influence of the glutamatergic lateral PBN neurons probably for the regulation of arousal and waking.", "classifications": [ { "id": "Yokota", "label": "Group Yokota", "parent": "Enomoto", "type": "group" }, { "id": "Enomoto", "label": "Team Enomoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Jian-Guo", "last_name": "Niu", "name": null }, { "creator_type": "author", "first_name": "Shigefumi", "last_name": "Yokota", "name": null }, { "creator_type": "author", "first_name": "Toshiko", "last_name": "Tsumori", "name": null }, { "creator_type": "author", "first_name": "Yi", "last_name": "Qin", "name": null }, { "creator_type": "author", "first_name": "Yukihiko", "last_name": "Yasui", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.brainres.2010.08.056" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "20735997" } }, "mesh": [ { "descriptor": "Afferent Pathways", "descriptor_ui": "D000344", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Biotin", "descriptor_ui": "D001710", "major_topic": false }, { "descriptor": "Cell Count", "descriptor_ui": "D002452", "major_topic": false }, { "descriptor": "Cholera Toxin", "descriptor_ui": "D002772", "major_topic": false }, { "descriptor": "Dextrans", "descriptor_ui": "D003911", "major_topic": false }, { "descriptor": "Glutamate Decarboxylase", "descriptor_ui": "D005968", "major_topic": false }, { "descriptor": "Glutamic Acid", "descriptor_ui": "D018698", "major_topic": false }, { "descriptor": "Hypothalamus", "descriptor_ui": "D007031", "major_topic": false }, { "descriptor": "Intracellular Signaling Peptides and Proteins", "descriptor_ui": "D047908", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Microscopy, Electron, Transmission", "descriptor_ui": "D046529", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Neuropeptides", "descriptor_ui": "D009479", "major_topic": false }, { "descriptor": "Orexins", "descriptor_ui": "D000068797", "major_topic": false }, { "descriptor": "Pons", "descriptor_ui": "D011149", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "RNA, Messenger", "descriptor_ui": "D012333", "major_topic": false }, { "descriptor": "Synapses", "descriptor_ui": "D013569", "major_topic": false }, { "descriptor": "Vesicular Glutamate Transport Protein 2", "descriptor_ui": "D050599", "major_topic": false } ], "publication": { "conference_name": null, "date": "2010 Oct 28", "date_precision": "day", "issue": "", "normalized_date": "2010-10-28", "pages": "110-122", "proceedings_title": null, "publisher": "", "title": "Brain research", "volume": "1358", "year": 2010 }, "ssbd": { "database": [], "repository": [] }, "title": "Glutamatergic lateral parabrachial neurons innervate orexin-containing hypothalamic neurons in the rat.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "We demonstrate high-resolution fluorescence microscopy based on a cyclic sequential multiphoton (CSM) process, which gives rise to fluorescence emission following a sequence of cyclic transitions between the bright and dark states of a fluorophore induced by pump and reverse light. By temporally modulating the reverse intensity, we can extract the fluorescence signal generated through the CSM process. We show that the demodulated fluorescence signal is nonlinearly proportional to the excitation intensities and it gives a higher spatial resolution than that of a confocal microscope.", "classifications": [ { "id": "Isobe", "label": "Group Isobe", "parent": "Imayoshi", "type": "group" }, { "id": "Imayoshi", "label": "Team Imayoshi", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Keisuke", "last_name": "Isobe", "name": null }, { "creator_type": "author", "first_name": "Akira", "last_name": "Suda", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Fumihiko", "last_name": "Kannari", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Kawano", "name": null }, { "creator_type": "author", "first_name": "Hideaki", "last_name": "Mizuno", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Miyawaki", "name": null }, { "creator_type": "author", "first_name": "Katsumi", "last_name": "Midorikawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1364/boe.1.000791" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "21258510" } }, "mesh": [], "publication": { "conference_name": null, "date": "2010 Oct 01", "date_precision": "day", "issue": "3", "normalized_date": "2010-10-01", "pages": "791-797", "proceedings_title": null, "publisher": "", "title": "Biomedical Optics Express", "volume": "1", "year": 2010 }, "ssbd": { "database": [], "repository": [] }, "title": "High-resolution fluorescence microscopy based on a cyclic sequential multiphoton process.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Identifying the targets of bioactive compounds is a major challenge in chemical biological research. Here, we identified the functional target of the natural bioactive compound glucopiericidin A (GPA) through metabolomic analysis. We isolated GPA while screening microbial samples for a filopodia protrusion inhibitor. Interestingly, GPA alone did not inhibit filopodia protrusion, but synergistically inhibit protrusion with the mitochondrial respiration inhibitor, piericidin A (PA). These results suggested that GPA might inhibit glycolysis. Capillary electrophoresis time-of-flight mass spectrometry (CE-TOFMS) provided strong evidence that GPA suppresses glycolysis by functionally targeting the glucose transporter. GPA may therefore serve as a glucose transporter chemical probe. Simultaneous inhibition of both glycolysis and mitochondrial respiration dramatically decreased intracellular ATP levels, indicating that GPA inhibits ATP-dependent filopodia protrusion with PA. Our results represent a challenge of molecular target identification using metabolomic analysis.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Mitsuhiro", "last_name": "Kitagawa", "name": null }, { "creator_type": "author", "first_name": "Satsuki", "last_name": "Ikeda", "name": null }, { "creator_type": "author", "first_name": "Etsu", "last_name": "Tashiro", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Masaya", "last_name": "Imoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.chembiol.2010.06.017" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "20851348" } }, "mesh": [ { "descriptor": "Adenosine Triphosphate", "descriptor_ui": "D000255", "major_topic": false }, { "descriptor": "Aminoglycosides", "descriptor_ui": "D000617", "major_topic": false }, { "descriptor": "Anti-Bacterial Agents", "descriptor_ui": "D000900", "major_topic": false }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Electrophoresis, Capillary", "descriptor_ui": "D019075", "major_topic": false }, { "descriptor": "Glucose Transport Proteins, Facilitative", "descriptor_ui": "D051246", "major_topic": false }, { "descriptor": "Glycolysis", "descriptor_ui": "D006019", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mass Spectrometry", "descriptor_ui": "D013058", "major_topic": false }, { "descriptor": "Metabolome", "descriptor_ui": "D055442", "major_topic": true }, { "descriptor": "Pseudopodia", "descriptor_ui": "D011554", "major_topic": false }, { "descriptor": "Pyridines", "descriptor_ui": "D011725", "major_topic": false } ], "publication": { "conference_name": null, "date": "2010 Sep 24", "date_precision": "day", "issue": "9", "normalized_date": "2010-09-24", "pages": "989-998", "proceedings_title": null, "publisher": "", "title": "Chemistry & biology", "volume": "17", "year": 2010 }, "ssbd": { "database": [], "repository": [] }, "title": "Metabolomic identification of the target of the filopodia protrusion inhibitor glucopiericidin A.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Regulatory relations between biological molecules constitute complex network systems and realize diverse biological functions through the dynamics of molecular activities. However, we currently have very little understanding of the relationship between the structure of a regulatory network and its dynamical properties. In this paper we introduce a new method, named \"linkage logic\" to analyze the dynamics of network systems. By this method, we can restrict possible steady states of a given complex network system from the knowledge of regulatory linkages alone. The regulatory linkage simply specifies the list of variables that affect the dynamics of each variable. We formalize two aspects of the linkage logic: the \"Principle of Compatibility\" determines the upper limit of the diversity of possible steady states of the dynamics realized by a given network; the \"Principle of Dependency\" determines the possible combinations of states of the system. By combining these two aspects, (i) for a given network, we can identify a cluster of nodes that gives an alternative representation of the steady states of the whole system, (ii) we can reduce a given complex network into a simpler one without loss of the ability to generate the diversity of steady states, (iii) we can examine the consistency between the structure of network and observed set of steady states, and (iv) sometimes we can predict unknown states or unknown regulations from an observed set of steady states alone. We illustrate the method by several applications to an experimentally determined regulatory network for biological functions.", "classifications": [ { "id": "Mochizuki", "label": "Group Mochizuki", "parent": "Eiraku", "type": "group" }, { "id": "Eiraku", "label": "Team Eiraku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Atsushi", "last_name": "Mochizuki", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Saito", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.jtbi.2010.06.007" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "20553943" } }, "mesh": [ { "descriptor": "Algorithms", "descriptor_ui": "D000465", "major_topic": true }, { "descriptor": "Computer Simulation", "descriptor_ui": "D003198", "major_topic": false }, { "descriptor": "Gene Regulatory Networks", "descriptor_ui": "D053263", "major_topic": false }, { "descriptor": "Models, Biological", "descriptor_ui": "D008954", "major_topic": true }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false } ], "publication": { "conference_name": null, "date": "2010 Sep 21", "date_precision": "day", "issue": "2", "normalized_date": "2010-09-21", "pages": "323-335", "proceedings_title": null, "publisher": "", "title": "Journal of theoretical biology", "volume": "266", "year": 2010 }, "ssbd": { "database": [], "repository": [] }, "title": "Analyzing steady states of dynamics of bio-molecules from the structure of regulatory networks.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "How global organ asymmetry and individual cell polarity are connected to each other is a central question in studying planar cell polarity (PCP). In the Drosophila wing, which develops PCP along its proximal-distal (P-D) axis, we previously proposed that the core PCP mediator Frizzled redistributes distally in a microtubule (MT)-dependent manner. Here we performed organ-wide analysis of MT dynamics by introducing quantitative in vivo imaging. We observed MTs aligning along the P-D axis at the onset of redistribution and a small but significant excess of + ends-distal MTs in the proximal region of the wing. This characteristic alignment and asymmetry of MT growth was controlled by atypical cadherins Dachsous (Ds) and Fat (Ft). Furthermore, the action of Ft was mediated in part by PAR-1. All these data support the idea that the active reorientation of MT growth adjusts cell polarity along the organ axis.", "classifications": [ { "id": "Kobayashi", "label": "Group Kobayashi", "parent": "Wakamoto", "type": "group" }, { "id": "Wakamoto", "label": "Team Wakamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Toshiyuki", "last_name": "Harumoto", "name": null }, { "creator_type": "author", "first_name": "Masayoshi", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Yuko", "last_name": "Shimada", "name": null }, { "creator_type": "author", "first_name": "Tetsuya J.", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Hiroki R.", "last_name": "Ueda", "name": null }, { "creator_type": "author", "first_name": "Bingwei", "last_name": "Lu", "name": null }, { "creator_type": "author", "first_name": "Tadashi", "last_name": "Uemura", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.devcel.2010.08.004" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "20817616" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cadherins", "descriptor_ui": "D015820", "major_topic": false }, { "descriptor": "Cell Adhesion Molecules", "descriptor_ui": "D015815", "major_topic": false }, { "descriptor": "Cell Polarity", "descriptor_ui": "D016764", "major_topic": true }, { "descriptor": "Drosophila melanogaster", "descriptor_ui": "D004331", "major_topic": false }, { "descriptor": "Drosophila Proteins", "descriptor_ui": "D029721", "major_topic": false }, { "descriptor": "Gene Expression Regulation, Developmental", "descriptor_ui": "D018507", "major_topic": false }, { "descriptor": "Glycogen Synthase Kinase 3", "descriptor_ui": "D038362", "major_topic": false }, { "descriptor": "Microtubules", "descriptor_ui": "D008870", "major_topic": false }, { "descriptor": "Morphogenesis", "descriptor_ui": "D009024", "major_topic": false }, { "descriptor": "Protein Serine-Threonine Kinases", "descriptor_ui": "D017346", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Subcellular Fractions", "descriptor_ui": "D013347", "major_topic": false }, { "descriptor": "Wings, Animal", "descriptor_ui": "D014921", "major_topic": false } ], "publication": { "conference_name": null, "date": "2010 Sep 14", "date_precision": "day", "issue": "3", "normalized_date": "2010-09-14", "pages": "389-401", "proceedings_title": null, "publisher": "", "title": "Developmental cell", "volume": "19", "year": 2010 }, "ssbd": { "database": [], "repository": [] }, "title": "Atypical Cadherins Dachsous and Fat Control Dynamics of Noncentrosomal Microtubules in Planar Cell Polarity.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "We demonstrate the measurement of two-photon excitation (TPE) spectra, used not only for fluorescence but also for photoconversion in green-to-red photoconvertible Kaede, using nonlinear Fourier-transform spectroscopy. It was found that in unphotoconverted Kaede, the TPE spectrum for photoconversion is much different to that for green-fluorescence. This is similar to the difference between the one-photon excitation of photoconversion in the neutral form and that of green-fluorescence in the ionized form.", "classifications": [ { "id": "Isobe", "label": "Group Isobe", "parent": "Imayoshi", "type": "group" }, { "id": "Imayoshi", "label": "Team Imayoshi", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Keisuke", "last_name": "Isobe", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Akira", "last_name": "Suda", "name": null }, { "creator_type": "author", "first_name": "Fumihiko", "last_name": "Kannari", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Kawano", "name": null }, { "creator_type": "author", "first_name": "Hideaki", "last_name": "Mizuno", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Miyawaki", "name": null }, { "creator_type": "author", "first_name": "Katsumi", "last_name": "Midorikawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1364/boe.1.000687" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "21258500" } }, "mesh": [], "publication": { "conference_name": null, "date": "2010 Sep 01", "date_precision": "day", "issue": "2", "normalized_date": "2010-09-01", "pages": "687-693", "proceedings_title": null, "publisher": "", "title": "Biomedical Optics Express", "volume": "1", "year": 2010 }, "ssbd": { "database": [], "repository": [] }, "title": "Measurement of two-photon excitation spectrum used to photoconvert a fluorescent protein (Kaede) by nonlinear Fourier-transform spectroscopy.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "A thorough understanding of the circadian clock requires qualitative evaluation of circadian clock gene expression. Thus far, no simple and effective method for detecting human clock gene expression has become available. This limitation has greatly hampered our understanding of human circadian rhythm. Here we report a convenient, reliable, and less invasive method for detecting human clock gene expression using biopsy samples of hair follicle cells from the head or chin. We show that the circadian phase of clock gene expression in hair follicle cells accurately reflects that of individual behavioral rhythms, demonstrating that this strategy is appropriate for evaluating the human peripheral circadian clock. Furthermore, using this method, we indicate that rotating shift workers suffer from a serious time lag between circadian gene expression rhythms and lifestyle. Qualitative evaluation of clock gene expression in hair follicle cells, therefore, may be an effective approach for studying the human circadian clock in the clinical setting.", "classifications": [ { "id": "Yamamoto", "label": "Group Yamamoto", "parent": "Toyoshima", "type": "group" }, { "id": "Toyoshima", "label": "Team Toyoshima", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Makoto", "last_name": "Akashi", "name": null }, { "creator_type": "author", "first_name": "Haruhiko", "last_name": "Soma", "name": null }, { "creator_type": "author", "first_name": "Takuro", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Asuka", "last_name": "Tsugitomi", "name": null }, { "creator_type": "author", "first_name": "Shiko", "last_name": "Yamashita", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Eisuke", "last_name": "Nishida", "name": null }, { "creator_type": "author", "first_name": "Akio", "last_name": "Yasuda", "name": null }, { "creator_type": "author", "first_name": "James K.", "last_name": "Liao", "name": null }, { "creator_type": "author", "first_name": "Koichi", "last_name": "Node", "name": null } ], "identifiers": { "doi": { "normalized": "10.1073/pnas.1003878107" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "20798039" } }, "mesh": [ { "descriptor": "Algorithms", "descriptor_ui": "D000465", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Biological Clocks", "descriptor_ui": "D001683", "major_topic": false }, { "descriptor": "Circadian Rhythm", "descriptor_ui": "D002940", "major_topic": false }, { "descriptor": "CLOCK Proteins", "descriptor_ui": "D056926", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Gene Expression Profiling", "descriptor_ui": "D020869", "major_topic": false }, { "descriptor": "Hair Follicle", "descriptor_ui": "D018859", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Models, Genetic", "descriptor_ui": "D008957", "major_topic": false }, { "descriptor": "Nuclear Receptor Subfamily 1, Group D, Member 1", "descriptor_ui": "D056953", "major_topic": false }, { "descriptor": "Oligonucleotide Array Sequence Analysis", "descriptor_ui": "D020411", "major_topic": false }, { "descriptor": "Period Circadian Proteins", "descriptor_ui": "D056950", "major_topic": false }, { "descriptor": "Receptors, Cytoplasmic and Nuclear", "descriptor_ui": "D018160", "major_topic": false }, { "descriptor": "Repressor Proteins", "descriptor_ui": "D012097", "major_topic": false }, { "descriptor": "Reproducibility of Results", "descriptor_ui": "D015203", "major_topic": false }, { "descriptor": "Reverse Transcriptase Polymerase Chain Reaction", "descriptor_ui": "D020133", "major_topic": false } ], "publication": { "conference_name": null, "date": "2010 Aug 31", "date_precision": "day", "issue": "35", "normalized_date": "2010-08-31", "pages": "15643-15648", "proceedings_title": null, "publisher": "", "title": "Proceedings of the National Academy of Sciences of the United States of America", "volume": "107", "year": 2010 }, "ssbd": { "database": [], "repository": [] }, "title": "Noninvasive method for assessing the human circadian clock using hair follicle cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "We discovered novel catalytic activities of two atypical NADPH-dependent oxidoreductases (EhNO1/2) from the enteric protozoan parasite Entamoeba histolytica. EhNO1/2 were previously annotated as the small subunit of glutamate synthase (glutamine:2-oxoglutarate amidotransferase) based on similarity to authentic bacterial homologs. As E. histolytica lacks the large subunit of glutamate synthase, EhNO1/2 were presumed to play an unknown role other than glutamine/glutamate conversion. Transcriptomic and quantitative reverse PCR analyses revealed that supplementation or deprivation of extracellular L-cysteine caused dramatic up- or down-regulation, respectively, of EhNO2, but not EhNO1 expression. Biochemical analysis showed that these FAD- and 2[4Fe-4S]-containing enzymes do not act as glutamate synthases, a conclusion which was supported by phylogenetic analyses. Rather, they catalyze the NADPH-dependent reduction of oxygen to hydrogen peroxide and L-cystine to L-cysteine and also function as ferric and ferredoxin-NADP(+) reductases. EhNO1/2 showed notable differences in substrate specificity and catalytic efficiency; EhNO1 had lower K(m) and higher k(cat)/K(m) values for ferric ion and ferredoxin than EhNO2, whereas EhNO2 preferred L-cystine as a substrate. In accordance with these properties, only EhNO1 was observed to physically interact with intrinsic ferredoxin. Interestingly, EhNO1/2 also reduced metronidazole, and E. histolytica transformants overexpressing either of these proteins were more sensitive to metronidazole, suggesting that EhNO1/2 are targets of this anti-amebic drug. To date, this is the first report to demonstrate that small subunit-like proteins of glutamate synthase could play an important role in redox maintenance, L-cysteine/L-cystine homeostasis, iron reduction, and the activation of metronidazole.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Ghulam", "last_name": "Jeelani", "name": null }, { "creator_type": "author", "first_name": "Afzal", "last_name": "Husain", "name": null }, { "creator_type": "author", "first_name": "Dan", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Vahab", "last_name": "Ali", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Suematsu", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Nozaki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1074/jbc.m110.106310" }, "pmcid": { "normalized": "PMC2930688" }, "pmid": { "normalized": "20592025" } }, "mesh": [ { "descriptor": "Amino Acid Sequence", "descriptor_ui": "D000595", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Antiprotozoal Agents", "descriptor_ui": "D000981", "major_topic": false }, { "descriptor": "Catalytic Domain", "descriptor_ui": "D020134", "major_topic": false }, { "descriptor": "Cysteine", "descriptor_ui": "D003545", "major_topic": false }, { "descriptor": "Entamoeba histolytica", "descriptor_ui": "D004748", "major_topic": false }, { "descriptor": "Enzyme Activation", "descriptor_ui": "D004789", "major_topic": false }, { "descriptor": "Flavin-Adenine Dinucleotide", "descriptor_ui": "D005182", "major_topic": false }, { "descriptor": "Iron", "descriptor_ui": "D007501", "major_topic": false }, { "descriptor": "Iron-Sulfur Proteins", "descriptor_ui": "D007506", "major_topic": false }, { "descriptor": "Metronidazole", "descriptor_ui": "D008795", "major_topic": false }, { "descriptor": "Molecular Sequence Data", "descriptor_ui": "D008969", "major_topic": false }, { "descriptor": "NADH, NADPH Oxidoreductases", "descriptor_ui": "D009247", "major_topic": false }, { "descriptor": "Oxidation-Reduction", "descriptor_ui": "D010084", "major_topic": false }, { "descriptor": "Protozoan Proteins", "descriptor_ui": "D015800", "major_topic": false }, { "descriptor": "Substrate Specificity", "descriptor_ui": "D013379", "major_topic": false } ], "publication": { "conference_name": null, "date": "2010 Aug 27", "date_precision": "day", "issue": "35", "normalized_date": "2010-08-27", "pages": "26889-26899", "proceedings_title": null, "publisher": "", "title": "The Journal of biological chemistry", "volume": "285", "year": 2010 }, "ssbd": { "database": [], "repository": [] }, "title": "Two atypical L-cysteine-regulated NADPH-dependent oxidoreductases involved in redox maintenance, L-cystine and iron reduction, and metronidazole activation in the enteric protozoan Entamoeba histolytica.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "A nitrated guanine nucleotide, 8-nitroguanosine 3′,5′-cyclic monophosphate (8-nitro-cGMP), is formed via nitric oxide (NO) and causes protein S-guanylation. However, intracellular 8-nitro-cGMP levels and mechanisms of formation of 8-nitro-cGMP and S-guanylation are yet to be identified. In this study, we precisely quantified NO-dependent formation of 8-nitro-cGMP in C6 glioma cells via liquid chromatography-tandem mass spectrometry. Treatment of cells with S-nitroso-N-acetylpenicillamine led to a rapid, transient increase in cGMP, after which 8-nitro-cGMP increased linearly up to a peak value comparable with that of cGMP at 24 h and declined thereafter. Markedly high levels (>40 μm) of 8-nitro-cGMP were also evident in C6 cells that had been stimulated to express inducible NO synthase with excessive NO production. The amount of 8-nitro-cGMP generated was comparable with or much higher than that of cGMP, whose production profile slightly preceded 8-nitro-cGMP formation in the activated inducible NO synthase-expressing cells. These unexpectedly large amounts of 8-nitro-cGMP suggest that GTP (a substrate of cGMP biosynthesis), rather than cGMP per se, may undergo guanine nitration. Also, 8-nitro-cGMP caused S-guanylation of KEAP1 in cells, which led to Nrf2 activation and subsequent induction of antioxidant enzymes, including heme oxygenase-1; thus, 8-nitro-cGMP protected cells against cytotoxic effects of hydrogen peroxide. Proteomic analysis for endogenously modified KEAP1 with matrix-assisted laser desorption/ionization time-of-flight-tandem mass spectrometry revealed that 8-nitro-cGMP S-guanylated the Cys434 of KEAP1. The present report is therefore the first substantial corroboration of the biological significance of cellular 8-nitro-cGMP formation and potential roles of 8-nitro-cGMP in the Nrf2-dependent antioxidant response.", "classifications": [ { "id": "Akaike", "label": "Group Akaike", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Shigemoto", "last_name": "Fujii", "name": null }, { "creator_type": "author", "first_name": "Tomohiro", "last_name": "Sawa", "name": null }, { "creator_type": "author", "first_name": "Hideshi", "last_name": "Ihara", "name": null }, { "creator_type": "author", "first_name": "Kit I.", "last_name": "Tong", "name": null }, { "creator_type": "author", "first_name": "Tomoaki", "last_name": "Ida", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Okamoto", "name": null }, { "creator_type": "author", "first_name": "Ahmed Khandaker", "last_name": "Ahtesham", "name": null }, { "creator_type": "author", "first_name": "Yu", "last_name": "Ishima", "name": null }, { "creator_type": "author", "first_name": "Hozumi", "last_name": "Motohashi", "name": null }, { "creator_type": "author", "first_name": "Masayuki", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Takaaki", "last_name": "Akaike", "name": null } ], "identifiers": { "doi": { "normalized": "10.1074/jbc.m110.145441" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "20498371" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Antioxidants", "descriptor_ui": "D000975", "major_topic": false }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Chromatography, Liquid", "descriptor_ui": "D002853", "major_topic": false }, { "descriptor": "Cyclic GMP", "descriptor_ui": "D006152", "major_topic": false }, { "descriptor": "Glioma", "descriptor_ui": "D005910", "major_topic": false }, { "descriptor": "Guanine", "descriptor_ui": "D006147", "major_topic": false }, { "descriptor": "Mass Spectrometry", "descriptor_ui": "D013058", "major_topic": false }, { "descriptor": "Nitric Oxide", "descriptor_ui": "D009569", "major_topic": false }, { "descriptor": "Oxidative Stress", "descriptor_ui": "D018384", "major_topic": false }, { "descriptor": "Protein Processing, Post-Translational", "descriptor_ui": "D011499", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Reactive Oxygen Species", "descriptor_ui": "D017382", "major_topic": false }, { "descriptor": "Tandem Mass Spectrometry", "descriptor_ui": "D053719", "major_topic": false } ], "publication": { "conference_name": null, "date": "2010 Jul 30", "date_precision": "day", "issue": "31", "normalized_date": "2010-07-30", "pages": "23970-23984", "proceedings_title": null, "publisher": "", "title": "The Journal of Biological Chemistry", "volume": "285", "year": 2010 }, "ssbd": { "database": [], "repository": [] }, "title": "The Critical Role of Nitric Oxide Signaling, via Protein S-Guanylation and Nitrated Cyclic GMP, in the Antioxidant Adaptive Response*.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Its high nutritional content and sensory characteristics make edamame a popular vegetable bean. However, because of its short shelf-life, it is important to optimize the storage conditions to maintain its quality during distribution to consumers. We focused on storage conditions to investigate the temporal changes in the metabolic profiles and sensory characteristics of edamame during transportation from the site of harvest to the site of purchase/consumption. We conducted metabolomic analysis and sensory evaluation tests of edamame stored for different lengths and at different temperatures. Charged metabolites were profiled by capillary electrophoresis-mass spectrometry, and free sugars were quantified by liquid chromatography-tandem mass spectrometry. In comparison to the gradual decrease in its sensory characteristics over time, the changes in metabolite profiles manifested four different patterns. In particular, changes in amino acid levels were related to sensory attributes. The downstream metabolites of shikimate as well as phospholipids and gamma-aminobutyric acid increased with increasing storage temperatures.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Masahiro", "last_name": "Sugimoto", "name": null }, { "creator_type": "author", "first_name": "Hajime", "last_name": "Goto", "name": null }, { "creator_type": "author", "first_name": "Kazuko", "last_name": "Otomo", "name": null }, { "creator_type": "author", "first_name": "Masanori", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Hiromi", "last_name": "Onuma", "name": null }, { "creator_type": "author", "first_name": "Asako", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Maki", "last_name": "Sugawara", "name": null }, { "creator_type": "author", "first_name": "Shinobu", "last_name": "Abe", "name": null }, { "creator_type": "author", "first_name": "Masaru", "last_name": "Tomita", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/jf101471d" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "20593783" } }, "mesh": [ { "descriptor": "Amino Acids", "descriptor_ui": "D000596", "major_topic": false }, { "descriptor": "Carbohydrate Metabolism", "descriptor_ui": "D050260", "major_topic": false }, { "descriptor": "Carbohydrates", "descriptor_ui": "D002241", "major_topic": false }, { "descriptor": "Chromatography, Liquid", "descriptor_ui": "D002853", "major_topic": false }, { "descriptor": "Fabaceae", "descriptor_ui": "D007887", "major_topic": false }, { "descriptor": "Food Handling", "descriptor_ui": "D005511", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mass Spectrometry", "descriptor_ui": "D013058", "major_topic": false }, { "descriptor": "Metabolomics", "descriptor_ui": "D055432", "major_topic": true }, { "descriptor": "Taste", "descriptor_ui": "D013649", "major_topic": true }, { "descriptor": "Temperature", "descriptor_ui": "D013696", "major_topic": false } ], "publication": { "conference_name": null, "date": "2010 Jul 28", "date_precision": "day", "issue": "14", "normalized_date": "2010-07-28", "pages": "8418-8425", "proceedings_title": null, "publisher": "", "title": "Journal of agricultural and food chemistry", "volume": "58", "year": 2010 }, "ssbd": { "database": [], "repository": [] }, "title": "Metabolomic profiles and sensory attributes of edamame under various storage duration and temperature conditions.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "In cellular signal transduction, the information in an external stimulus is encoded in temporal patterns in the activities of signaling molecules; for example, pulses of a stimulus may produce an increasing response or may produce pulsatile responses in the signaling molecules. Here, we show how the Akt pathway, which is involved in cell growth, specifically transmits temporal information contained in upstream signals to downstream effectors. We modeled the epidermal growth factor (EGF)-dependent Akt pathway in PC12 cells on the basis of experimental results. We obtained counterintuitive results indicating that the sizes of the peak amplitudes of receptor and downstream effector phosphorylation were decoupled; weak, sustained EGF receptor (EGFR) phosphorylation, rather than strong, transient phosphorylation, strongly induced phosphorylation of the ribosomal protein S6, a molecule downstream of Akt. Using frequency response analysis, we found that a three-component Akt pathway exhibited the property of a low-pass filter and that this property could explain decoupling of the peak amplitudes of receptor phosphorylation and that of downstream effectors. Furthermore, we found that lapatinib, an EGFR inhibitor used as an anticancer drug, converted strong, transient Akt phosphorylation into weak, sustained Akt phosphorylation, and, because of the low-pass filter characteristics of the Akt pathway, this led to stronger S6 phosphorylation than occurred in the absence of the inhibitor. Thus, an EGFR inhibitor can potentially act as a downstream activator of some effectors.", "classifications": [ { "id": "Kuroda", "label": "Group Kuroda", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Kazuhiro A.", "last_name": "Fujita", "name": null }, { "creator_type": "author", "first_name": "Yu", "last_name": "Toyoshima", "name": null }, { "creator_type": "author", "first_name": "Shinsuke", "last_name": "Uda", "name": null }, { "creator_type": "author", "first_name": "Yu-ichi", "last_name": "Ozaki", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Kubota", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Kuroda", "name": null } ], "identifiers": { "doi": { "normalized": "10.1126/scisignal.2000810" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "20664065" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Epidermal Growth Factor", "descriptor_ui": "D004815", "major_topic": false }, { "descriptor": "ErbB Receptors", "descriptor_ui": "D066246", "major_topic": false }, { "descriptor": "Immunoblotting", "descriptor_ui": "D015151", "major_topic": false }, { "descriptor": "Lapatinib", "descriptor_ui": "D000077341", "major_topic": false }, { "descriptor": "Models, Biological", "descriptor_ui": "D008954", "major_topic": false }, { "descriptor": "PC12 Cells", "descriptor_ui": "D016716", "major_topic": false }, { "descriptor": "Phosphorylation", "descriptor_ui": "D010766", "major_topic": false }, { "descriptor": "Protein Kinase Inhibitors", "descriptor_ui": "D047428", "major_topic": false }, { "descriptor": "Proto-Oncogene Proteins c-akt", "descriptor_ui": "D051057", "major_topic": false }, { "descriptor": "Quinazolines", "descriptor_ui": "D011799", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Ribosomal Protein S6", "descriptor_ui": "D038601", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": true } ], "publication": { "conference_name": null, "date": "2010 Jul 27", "date_precision": "day", "issue": "132", "normalized_date": "2010-07-27", "pages": "ra56", "proceedings_title": null, "publisher": "", "title": "Science signaling", "volume": "3", "year": 2010 }, "ssbd": { "database": [], "repository": [] }, "title": "Decoupling of receptor and downstream signals in the Akt pathway by its low-pass filter characteristics.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "It has long been presumed that after leaving the germinal centers (GCs), memory B cells colonize the marginal zone or join the recirculating pool. Here we demonstrate the preferential localization of nitrophenol-chicken γ-globulin-induced CD38+IgG1+ memory B cells adjacent to contracted GCs in the spleen. The memory B cells in this region proliferated after secondary immunization, a response that was abolished by depletion of CD4+ T cells. We also found that these IgG1+ memory B cells could present antigen on their surface, and that this activity was required for their activation. These results implicate this peri-GC region as an important site for survival and reactivation of memory B cells.", "classifications": [ { "id": "Sawano", "label": "Group Sawano", "parent": "Shintaku", "type": "group" }, { "id": "Shintaku", "label": "Team Shintaku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yuichi", "last_name": "Aiba", "name": null }, { "creator_type": "author", "first_name": "Kohei", "last_name": "Kometani", "name": null }, { "creator_type": "author", "first_name": "Megumi", "last_name": "Hamadate", "name": null }, { "creator_type": "author", "first_name": "Saya", "last_name": "Moriyama", "name": null }, { "creator_type": "author", "first_name": "Asako", "last_name": "Sakaue-Sawano", "name": null }, { "creator_type": "author", "first_name": "Michio", "last_name": "Tomura", "name": null }, { "creator_type": "author", "first_name": "Hervé", "last_name": "Luche", "name": null }, { "creator_type": "author", "first_name": "Hans Jörg", "last_name": "Fehling", "name": null }, { "creator_type": "author", "first_name": "Rafael", "last_name": "Casellas", "name": null }, { "creator_type": "author", "first_name": "Osami", "last_name": "Kanagawa", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Miyawaki", "name": null }, { "creator_type": "author", "first_name": "Tomohiro", "last_name": "Kurosaki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1073/pnas.1005443107" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "20547847" } }, "mesh": [ { "descriptor": "ADP-ribosyl Cyclase 1", "descriptor_ui": "D051997", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "B-Lymphocytes", "descriptor_ui": "D001402", "major_topic": false }, { "descriptor": "CD4-Positive T-Lymphocytes", "descriptor_ui": "D015496", "major_topic": false }, { "descriptor": "Chickens", "descriptor_ui": "D002645", "major_topic": false }, { "descriptor": "Flow Cytometry", "descriptor_ui": "D005434", "major_topic": false }, { "descriptor": "gamma-Globulins", "descriptor_ui": "D005719", "major_topic": false }, { "descriptor": "Germinal Center", "descriptor_ui": "D018858", "major_topic": false }, { "descriptor": "Immunization", "descriptor_ui": "D007114", "major_topic": false }, { "descriptor": "Immunoglobulin G", "descriptor_ui": "D007074", "major_topic": false }, { "descriptor": "Immunohistochemistry", "descriptor_ui": "D007150", "major_topic": false }, { "descriptor": "Immunologic Memory", "descriptor_ui": "D007156", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Mice, Transgenic", "descriptor_ui": "D008822", "major_topic": false }, { "descriptor": "Nitrophenols", "descriptor_ui": "D009596", "major_topic": false }, { "descriptor": "Phenylacetates", "descriptor_ui": "D010648", "major_topic": false }, { "descriptor": "Spleen", "descriptor_ui": "D013154", "major_topic": false } ], "publication": { "conference_name": null, "date": "2010 Jul 6", "date_precision": "day", "issue": "27", "normalized_date": "2010-07-06", "pages": "12192-12197", "proceedings_title": null, "publisher": "", "title": "Proceedings of the National Academy of Sciences of the United States of America", "volume": "107", "year": 2010 }, "ssbd": { "database": [], "repository": [] }, "title": "Preferential localization of IgG memory B cells adjacent to contracted germinal centers.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "We present measurements of two-photon excitation (TPE) spectra of various fluorescent proteins with nonlinear Fourier-transform spectroscopy. By using an ultrabroadband laser pulse with a spectrum ranging from 700 to 1100 nm, the absolute TPE spectra of six typical fluorescent proteins (SeBFP, Sapphire, eGFP, eCFP, Venus, DsRed) were measured with high spectral resolution.", "classifications": [ { "id": "Isobe", "label": "Group Isobe", "parent": "Imayoshi", "type": "group" }, { "id": "Imayoshi", "label": "Team Imayoshi", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Keisuke", "last_name": "Isobe", "name": null }, { "creator_type": "author", "first_name": "Akira", "last_name": "Suda", "name": null }, { "creator_type": "author", "first_name": "Fumihiko", "last_name": "Kannari", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Kawano", "name": null }, { "creator_type": "author", "first_name": "Hideaki", "last_name": "Mizuno", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Miyawaki", "name": null }, { "creator_type": "author", "first_name": "Katsumi", "last_name": "Midorikawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1364/ao.49.003323" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "20539351" } }, "mesh": [ { "descriptor": "Bacterial Proteins", "descriptor_ui": "D001426", "major_topic": false }, { "descriptor": "Fourier Analysis", "descriptor_ui": "D005583", "major_topic": false }, { "descriptor": "Green Fluorescent Proteins", "descriptor_ui": "D049452", "major_topic": false }, { "descriptor": "Lasers", "descriptor_ui": "D007834", "major_topic": false }, { "descriptor": "Luminescent Proteins", "descriptor_ui": "D008164", "major_topic": false }, { "descriptor": "Nonlinear Dynamics", "descriptor_ui": "D017711", "major_topic": false }, { "descriptor": "Optical Phenomena", "descriptor_ui": "D055620", "major_topic": false }, { "descriptor": "Photons", "descriptor_ui": "D017785", "major_topic": false }, { "descriptor": "Spectrometry, Fluorescence", "descriptor_ui": "D013050", "major_topic": false } ], "publication": { "conference_name": null, "date": "2010 Jun 10", "date_precision": "day", "issue": "17", "normalized_date": "2010-06-10", "pages": "3323-3329", "proceedings_title": null, "publisher": "", "title": "Applied optics", "volume": "49", "year": 2010 }, "ssbd": { "database": [], "repository": [] }, "title": "Measurement of two-photon excitation spectra of fluorescent proteins with nonlinear Fourier-transform spectroscopy.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Decision making in a noisy and dynamically changing environment is a fundamental task for a cell. To choose appropriate decisions over time, a cell must be equipped with intracellular kinetics that can conduct dynamic and efficient decision making. By using the theory of sequential inference, I demonstrate that dynamic Bayesian decision making can be implemented by an intracellular kinetics with a dual positive feedback structure. I also show that the combination of linear instantaneous and nonlinear stationary sensitivities to the input dominantly contributes to decision making efficiency, and that the state-dependent sensitivity change further suppresses noisy response. The statistical principles underlying these two factors are further clarified to be a log-likelihood-dependent quantification of the input information and uncertainty-dependent sensitivity control.", "classifications": [ { "id": "Kobayashi", "label": "Group Kobayashi", "parent": "Wakamoto", "type": "group" }, { "id": "Wakamoto", "label": "Team Wakamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Tetsuya J.", "last_name": "Kobayashi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1103/physrevlett.104.228104" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "20867209" } }, "mesh": [ { "descriptor": "Bayes Theorem", "descriptor_ui": "D001499", "major_topic": false }, { "descriptor": "Feedback, Physiological", "descriptor_ui": "D025461", "major_topic": false }, { "descriptor": "Intracellular Space", "descriptor_ui": "D042541", "major_topic": false }, { "descriptor": "Kinetics", "descriptor_ui": "D007700", "major_topic": false }, { "descriptor": "Models, Biological", "descriptor_ui": "D008954", "major_topic": true } ], "publication": { "conference_name": null, "date": "2010 Jun 4", "date_precision": "day", "issue": "22", "normalized_date": "2010-06-04", "pages": "228104", "proceedings_title": null, "publisher": "", "title": "Physical review letters", "volume": "104", "year": 2010 }, "ssbd": { "database": [], "repository": [] }, "title": "Implementation of dynamic Bayesian decision making by intracellular kinetics.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "In the social amoebae Dictyostelium discoideum, periodic synthesis and release of extracellular cyclic adenosine 3',5'-monophosphate (cAMP) guide cell aggregation and commitment to form fruiting bodies. It is unclear whether these oscillations are an intrinsic property of individual cells or if they exist only as a population-level phenomenon. Here, we showed by live-cell imaging of intact cell populations that pulses originate from a discrete location despite constant exchange of cells to and from the region. In a perfusion chamber, both isolated single cells and cell populations switched from quiescence to rhythmic activity depending on the concentration of extracellular cAMP. A quantitative analysis showed that stochastic pulsing of individual cells below the threshold concentration of extracellular cAMP plays a critical role in the onset of collective behavior.", "classifications": [ { "id": "Fujimoto", "label": "Group Fujimoto", "parent": "Ueda", "type": "group" }, { "id": "Sawai", "label": "Group Sawai", "parent": "Sawai", "type": "group" }, { "id": "Sawai", "label": "Team Sawai", "type": "team" }, { "id": "Ueda", "label": "Team Ueda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Thomas", "last_name": "Gregor", "name": null }, { "creator_type": "author", "first_name": "Koichi", "last_name": "Fujimoto", "name": null }, { "creator_type": "author", "first_name": "Noritaka", "last_name": "Masaki", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Sawai", "name": null } ], "identifiers": { "doi": { "normalized": "10.1126/science.1183415" }, "pmcid": { "normalized": "PMC3120019" }, "pmid": { "normalized": "20413456" } }, "mesh": [ { "descriptor": "3',5'-Cyclic-AMP Phosphodiesterases", "descriptor_ui": "D015105", "major_topic": false }, { "descriptor": "Adenylyl Cyclases", "descriptor_ui": "D000262", "major_topic": false }, { "descriptor": "Cell Aggregation", "descriptor_ui": "D002449", "major_topic": false }, { "descriptor": "Cell Count", "descriptor_ui": "D002452", "major_topic": false }, { "descriptor": "Cyclic AMP", "descriptor_ui": "D000242", "major_topic": false }, { "descriptor": "Cyclic AMP-Dependent Protein Kinases", "descriptor_ui": "D017868", "major_topic": false }, { "descriptor": "Cytosol", "descriptor_ui": "D003600", "major_topic": false }, { "descriptor": "Dictyostelium", "descriptor_ui": "D004023", "major_topic": false }, { "descriptor": "Fluorescence Resonance Energy Transfer", "descriptor_ui": "D031541", "major_topic": false }, { "descriptor": "Models, Biological", "descriptor_ui": "D008954", "major_topic": false }, { "descriptor": "Periodicity", "descriptor_ui": "D010507", "major_topic": false }, { "descriptor": "Protozoan Proteins", "descriptor_ui": "D015800", "major_topic": false }, { "descriptor": "Quorum Sensing", "descriptor_ui": "D053038", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Stochastic Processes", "descriptor_ui": "D013269", "major_topic": false } ], "publication": { "conference_name": null, "date": "2010 May 21", "date_precision": "day", "issue": "5981", "normalized_date": "2010-05-21", "pages": "1021-1025", "proceedings_title": null, "publisher": "", "title": "Science (New York, N.Y.)", "volume": "328", "year": 2010 }, "ssbd": { "database": [], "repository": [] }, "title": "The onset of collective behavior in social amoebae.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Pertussis toxin (PTX) is recognized as a specific tool that uncouples receptors from G(i) and G(o) through ADP-ribosylation. During the study analyzing the effects of PTX on Ang II type 1 receptor (AT1R) function in cardiac fibroblasts, we found that PTX increases the number of AT1Rs and enhances AT1R-mediated response. Microarray analysis revealed that PTX increases the induction of interleukin (IL)-1beta among cytokines. Inhibition of IL-1beta suppressed the enhancement of AT1R-mediated response by PTX. PTX increased the expression of IL-1beta and AT1R through NF-kappaB, and a small GTP-binding protein, Rac, mediated PTX-induced NF-kappaB activation through NADPH oxidase-dependent production of reactive oxygen species. PTX induced biphasic increases in Rac activity, and the Rac activation in a late but not an early phase was suppressed by IL-1beta siRNA, suggesting that IL-1beta-induced Rac activation contributes to the amplification of Rac-dependent signaling induced by PTX. Furthermore, inhibition of TLR4 (Toll-like receptor 4) abolished PTX-induced Rac activation and enhancement of AT1R function. However, ADP-ribosylation of G(i)/G(o) by PTX was not affected by inhibition of TLR4. Thus, PTX binds to two receptors; one is TLR4, which activates Rac, and another is the binding site that is required for ADP-ribosylation of G(i)/G(o).", "classifications": [ { "id": "Nishida", "label": "Group Nishida", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Motohiro", "last_name": "Nishida", "name": null }, { "creator_type": "author", "first_name": "Reiko", "last_name": "Suda", "name": null }, { "creator_type": "author", "first_name": "Yuichi", "last_name": "Nagamatsu", "name": null }, { "creator_type": "author", "first_name": "Shihori", "last_name": "Tanabe", "name": null }, { "creator_type": "author", "first_name": "Naoya", "last_name": "Onohara", "name": null }, { "creator_type": "author", "first_name": "Michio", "last_name": "Nakaya", "name": null }, { "creator_type": "author", "first_name": "Yasunori", "last_name": "Kanaho", "name": null }, { "creator_type": "author", "first_name": "Takahiro", "last_name": "Shibata", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Uchida", "name": null }, { "creator_type": "author", "first_name": "Hideki", "last_name": "Sumimoto", "name": null }, { "creator_type": "author", "first_name": "Yoji", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Kurose", "name": null } ], "identifiers": { "doi": { "normalized": "10.1074/jbc.m109.076232" }, "pmcid": { "normalized": "PMC2865339" }, "pmid": { "normalized": "20231290" } }, "mesh": [ { "descriptor": "Angiotensin I", "descriptor_ui": "D000803", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Interleukin-1", "descriptor_ui": "D007375", "major_topic": false }, { "descriptor": "Myocardium", "descriptor_ui": "D009206", "major_topic": false }, { "descriptor": "Pertussis Toxin", "descriptor_ui": "D037342", "major_topic": false }, { "descriptor": "rac GTP-Binding Proteins", "descriptor_ui": "D020744", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Rats, Sprague-Dawley", "descriptor_ui": "D017207", "major_topic": false }, { "descriptor": "Reactive Oxygen Species", "descriptor_ui": "D017382", "major_topic": false }, { "descriptor": "Receptors, Angiotensin", "descriptor_ui": "D011945", "major_topic": false }, { "descriptor": "Toll-Like Receptors", "descriptor_ui": "D051193", "major_topic": false }, { "descriptor": "Up-Regulation", "descriptor_ui": "D015854", "major_topic": false } ], "publication": { "conference_name": null, "date": "2010 May 14", "date_precision": "day", "issue": "20", "normalized_date": "2010-05-14", "pages": "15268-15277", "proceedings_title": null, "publisher": "", "title": "The Journal of biological chemistry", "volume": "285", "year": 2010 }, "ssbd": { "database": [], "repository": [] }, "title": "Pertussis toxin up-regulates angiotensin type 1 receptors through Toll-like receptor 4-mediated Rac activation.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Chaperonins are absolutely required for the folding of a subset of proteins in the cell. An earlier proteome-wide analysis of Escherichia coli chaperonin GroEL/GroES (GroE) interactors predicted obligate chaperonin substrates, which were termed Class III substrates. However, the requirement of chaperonins for in vivo folding has not been fully examined. Here, we comprehensively assessed the chaperonin requirement using a conditional GroE expression strain, and concluded that only ∼60% of Class III substrates are bona fide obligate GroE substrates in vivo. The in vivo obligate substrates, combined with the newly identified obligate substrates, were termed Class IV substrates. Class IV substrates are restricted to proteins with molecular weights that could be encapsulated in the chaperonin cavity, are enriched in alanine/glycine residues, and have a strong structural preference for aggregation-prone folds. Notably, ∼70% of the Class IV substrates appear to be metabolic enzymes, supporting a hypothetical role of GroE in enzyme evolution.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Kei", "last_name": "Fujiwara", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Ishihama", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Nakahigashi", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Hideki", "last_name": "Taguchi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/emboj.2010.52" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "20360681" } }, "mesh": [ { "descriptor": "Amino Acid Sequence", "descriptor_ui": "D000595", "major_topic": false }, { "descriptor": "Chaperonin 60", "descriptor_ui": "D018834", "major_topic": false }, { "descriptor": "Escherichia coli", "descriptor_ui": "D004926", "major_topic": false }, { "descriptor": "Escherichia coli Proteins", "descriptor_ui": "D029968", "major_topic": false }, { "descriptor": "Gene Expression", "descriptor_ui": "D015870", "major_topic": false }, { "descriptor": "Metabolomics", "descriptor_ui": "D055432", "major_topic": false }, { "descriptor": "Protein Folding", "descriptor_ui": "D017510", "major_topic": false }, { "descriptor": "Proteomics", "descriptor_ui": "D040901", "major_topic": false }, { "descriptor": "Substrate Specificity", "descriptor_ui": "D013379", "major_topic": false } ], "publication": { "conference_name": null, "date": "2010 May 05", "date_precision": "day", "issue": "9", "normalized_date": "2010-05-05", "pages": "1552-1564", "proceedings_title": null, "publisher": "", "title": "The EMBO Journal", "volume": "29", "year": 2010 }, "ssbd": { "database": [], "repository": [] }, "title": "A systematic survey of in vivo obligate chaperonin-dependent substrates.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Precise temporal coordination of gene expression is crucial for many developmental processes. One central question in developmental biology is how such coordinated expression patterns are robustly controlled. During embryonic development of the Drosophila central nervous system, neural stem cells called neuroblasts express a group of genes in a definite order, which leads to the diversity of cell types. We produced all possible regulatory networks of these genes and examined their expression dynamics numerically. From the analysis, we identified requisite regulations and predicted an unknown factor to reproduce known expression profiles caused by loss-of-function or overexpression of the genes in vivo, as well as in the wild type. Following this, we evaluated the stability of the actual Drosophila network for sequential expression. This network shows the highest robustness against parameter variations and gene expression fluctuations among the possible networks that reproduce the expression profiles. We propose a regulatory module composed of three types of regulations that is responsible for precise sequential expression. This study suggests that the Drosophila network for sequential expression has evolved to generate the robust temporal expression for neuronal specification.", "classifications": [ { "id": "Ishihara", "label": "Group Ishihara", "parent": "Sawai", "type": "group" }, { "id": "Sawai", "label": "Team Sawai", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Akihiko", "last_name": "Nakajima", "name": null }, { "creator_type": "author", "first_name": "Takako", "last_name": "Isshiki", "name": null }, { "creator_type": "author", "first_name": "Kunihiko", "last_name": "Kaneko", "name": null }, { "creator_type": "author", "first_name": "Shuji", "last_name": "Ishihara", "name": null } ], "identifiers": { "doi": { "normalized": "10.1371/journal.pcbi.1000760" }, "pmcid": { "normalized": "PMC2861627" }, "pmid": { "normalized": "20454677" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Body Patterning", "descriptor_ui": "D019521", "major_topic": false }, { "descriptor": "Drosophila", "descriptor_ui": "D004330", "major_topic": false }, { "descriptor": "Gene Expression Profiling", "descriptor_ui": "D020869", "major_topic": false }, { "descriptor": "Gene Expression Regulation", "descriptor_ui": "D005786", "major_topic": false }, { "descriptor": "Gene Regulatory Networks", "descriptor_ui": "D053263", "major_topic": true }, { "descriptor": "Models, Biological", "descriptor_ui": "D008954", "major_topic": false }, { "descriptor": "Models, Statistical", "descriptor_ui": "D015233", "major_topic": false }, { "descriptor": "Neurogenesis", "descriptor_ui": "D055495", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Regression Analysis", "descriptor_ui": "D012044", "major_topic": false }, { "descriptor": "Stem Cells", "descriptor_ui": "D013234", "major_topic": false }, { "descriptor": "Systems Biology", "descriptor_ui": "D049490", "major_topic": false }, { "descriptor": "Time Factors", "descriptor_ui": "D013997", "major_topic": false } ], "publication": { "conference_name": null, "date": "2010 Apr 29", "date_precision": "day", "issue": "4", "normalized_date": "2010-04-29", "pages": "e1000760", "proceedings_title": null, "publisher": "", "title": "PLoS computational biology", "volume": "6", "year": 2010 }, "ssbd": { "database": [], "repository": [] }, "title": "Robustness under functional constraint: the genetic network for temporal expression in Drosophila neurogenesis.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Activation of Ca(2+) signaling induced by receptor stimulation and mechanical stress plays a critical role in the development of cardiac hypertrophy. A canonical transient receptor potential protein subfamily member, TRPC6, which is activated by diacylglycerol and mechanical stretch, works as an upstream regulator of the Ca(2+) signaling pathway. Although activation of protein kinase G (PKG) inhibits TRPC6 channel activity and cardiac hypertrophy, respectively, it is unclear whether PKG suppresses cardiac hypertrophy through inhibition of TRPC6. Here, we show that inhibition of cGMP-selective PDE5 (phosphodiesterase 5) suppresses endothelin-1-, diacylglycerol analog-, and mechanical stretch-induced hypertrophy through inhibition of Ca(2+) influx in rat neonatal cardiomyocytes. Inhibition of PDE5 suppressed the increase in frequency of Ca(2+) spikes induced by agonists or mechanical stretch. However, PDE5 inhibition did not suppress the hypertrophic responses induced by high KCl or the activation of protein kinase C, suggesting that PDE5 inhibition suppresses Ca(2+) influx itself or molecule(s) upstream of Ca(2+) influx. PKG activated by PDE5 inhibition phosphorylated TRPC6 proteins at Thr(69) and prevented TRPC6-mediated Ca(2+) influx. Substitution of Ala for Thr(69) in TRPC6 abolished the anti-hypertrophic effects of PDE5 inhibition. In addition, chronic PDE5 inhibition by oral sildenafil treatment actually induced TRPC6 phosphorylation in mouse hearts. Knockdown of RGS2 (regulator of G protein signaling 2) and RGS4, both of which are activated by PKG to reduce G alpha(q)-mediated signaling, did not affect the suppression of receptor-activated Ca(2+) influx by PDE5 inhibition. These results suggest that phosphorylation and functional suppression of TRPC6 underlie prevention of pathological hypertrophy by PDE5 inhibition.", "classifications": [ { "id": "Nishida", "label": "Group Nishida", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Motohiro", "last_name": "Nishida", "name": null }, { "creator_type": "author", "first_name": "Kenta", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Yoji", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Michio", "last_name": "Nakaya", "name": null }, { "creator_type": "author", "first_name": "Naoyuki", "last_name": "Kitajima", "name": null }, { "creator_type": "author", "first_name": "Tomomi", "last_name": "Ide", "name": null }, { "creator_type": "author", "first_name": "Ryuji", "last_name": "Inoue", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Kurose", "name": null } ], "identifiers": { "doi": { "normalized": "10.1074/jbc.m109.074104" }, "pmcid": { "normalized": "PMC2857061" }, "pmid": { "normalized": "20177073" } }, "mesh": [ { "descriptor": "Amino Acid Substitution", "descriptor_ui": "D019943", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Calcium", "descriptor_ui": "D002118", "major_topic": false }, { "descriptor": "Calcium Signaling", "descriptor_ui": "D020013", "major_topic": true }, { "descriptor": "Cardiomegaly", "descriptor_ui": "D006332", "major_topic": false }, { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "Cyclic GMP-Dependent Protein Kinases", "descriptor_ui": "D017869", "major_topic": false }, { "descriptor": "Cyclic Nucleotide Phosphodiesterases, Type 5", "descriptor_ui": "D054706", "major_topic": false }, { "descriptor": "Diglycerides", "descriptor_ui": "D004075", "major_topic": false }, { "descriptor": "Enzyme Activation", "descriptor_ui": "D004789", "major_topic": false }, { "descriptor": "Gene Knockdown Techniques", "descriptor_ui": "D055785", "major_topic": false }, { "descriptor": "GTP-Binding Protein alpha Subunits, Gq-G11", "descriptor_ui": "D043802", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mutation, Missense", "descriptor_ui": "D020125", "major_topic": false }, { "descriptor": "Myocytes, Cardiac", "descriptor_ui": "D032383", "major_topic": false }, { "descriptor": "Phosphodiesterase 5 Inhibitors", "descriptor_ui": "D058986", "major_topic": false }, { "descriptor": "Phosphodiesterase Inhibitors", "descriptor_ui": "D010726", "major_topic": false }, { "descriptor": "Piperazines", "descriptor_ui": "D010879", "major_topic": false }, { "descriptor": "Potassium Chloride", "descriptor_ui": "D011189", "major_topic": false }, { "descriptor": "Protein Kinase C", "descriptor_ui": "D011493", "major_topic": false }, { "descriptor": "Purines", "descriptor_ui": "D011687", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Sildenafil Citrate", "descriptor_ui": "D000068677", "major_topic": false }, { "descriptor": "Sulfones", "descriptor_ui": "D013450", "major_topic": false }, { "descriptor": "TRPC Cation Channels", "descriptor_ui": "D050052", "major_topic": false }, { "descriptor": "TRPC6 Cation Channel", "descriptor_ui": "D000074287", "major_topic": false } ], "publication": { "conference_name": null, "date": "2010 Apr 23", "date_precision": "day", "issue": "17", "normalized_date": "2010-04-23", "pages": "13244-13253", "proceedings_title": null, "publisher": "", "title": "The Journal of biological chemistry", "volume": "285", "year": 2010 }, "ssbd": { "database": [], "repository": [] }, "title": "Phosphorylation of TRPC6 channels at Thr69 is required for anti-hypertrophic effects of phosphodiesterase 5 inhibition.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: Modeling of cellular functions on the basis of experimental observation is increasingly common in the field of cellular signaling. However, such modeling requires a large amount of quantitative data of signaling events with high spatio-temporal resolution. A novel technique which allows us to obtain such data is needed for systems biology of cellular signaling. METHODOLOGY/PRINCIPAL FINDINGS: We developed a fully automatable assay technique, termed quantitative image cytometry (QIC), which integrates a quantitative immunostaining technique and a high precision image-processing algorithm for cell identification. With the aid of an automated sample preparation system, this device can quantify protein expression, phosphorylation and localization with subcellular resolution at one-minute intervals. The signaling activities quantified by the assay system showed good correlation with, as well as comparable reproducibility to, western blot analysis. Taking advantage of the high spatio-temporal resolution, we investigated the signaling dynamics of the ERK pathway in PC12 cells. CONCLUSIONS/SIGNIFICANCE: The QIC technique appears as a highly quantitative and versatile technique, which can be a convenient replacement for the most conventional techniques including western blot, flow cytometry and live cell imaging. Thus, the QIC technique can be a powerful tool for investigating the systems biology of cellular signaling.", "classifications": [ { "id": "Kuroda", "label": "Group Kuroda", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yu-ichi", "last_name": "Ozaki", "name": null }, { "creator_type": "author", "first_name": "Shinsuke", "last_name": "Uda", "name": null }, { "creator_type": "author", "first_name": "Takeshi H.", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Jaehoon", "last_name": "Chung", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Kubota", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Kuroda", "name": null } ], "identifiers": { "doi": { "normalized": "10.1371/journal.pone.0009955" }, "pmcid": { "normalized": "PMC2848603" }, "pmid": { "normalized": "20376360" } }, "mesh": [ { "descriptor": "Algorithms", "descriptor_ui": "D000465", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Automation", "descriptor_ui": "D001331", "major_topic": false }, { "descriptor": "Extracellular Signal-Regulated MAP Kinases", "descriptor_ui": "D048049", "major_topic": false }, { "descriptor": "Image Cytometry", "descriptor_ui": "D019044", "major_topic": false }, { "descriptor": "Image Processing, Computer-Assisted", "descriptor_ui": "D007091", "major_topic": false }, { "descriptor": "Immunohistochemistry", "descriptor_ui": "D007150", "major_topic": false }, { "descriptor": "PC12 Cells", "descriptor_ui": "D016716", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": true }, { "descriptor": "Systems Biology", "descriptor_ui": "D049490", "major_topic": false }, { "descriptor": "Time Factors", "descriptor_ui": "D013997", "major_topic": false } ], "publication": { "conference_name": null, "date": "2010 Apr 1", "date_precision": "day", "issue": "4", "normalized_date": "2010-04-01", "pages": "e9955", "proceedings_title": null, "publisher": "", "title": "PloS one", "volume": "5", "year": 2010 }, "ssbd": { "database": [], "repository": [] }, "title": "A quantitative image cytometry technique for time series or population analyses of signaling networks.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The first total synthesis of (+)-chaetocin has been accomplished in nine steps starting from known N-Cbz-N-Me-serine using radical alpha-bromination reaction of diketopiperazine 10 and Co(I)-mediated reductive dimerization reaction of 12 as key reactions. The enantiomers show comparable inhibitory activity toward histone methyltransferase (HMT) G9a, but analogues without the sulfur functionality are inactive.", "classifications": [ { "id": "Sodeoka", "label": "Group Sodeoka", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Eriko", "last_name": "Iwasa", "name": null }, { "creator_type": "author", "first_name": "Yoshitaka", "last_name": "Hamashima", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Fujishiro", "name": null }, { "creator_type": "author", "first_name": "Eisuke", "last_name": "Higuchi", "name": null }, { "creator_type": "author", "first_name": "Akihiro", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Minoru", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Mikiko", "last_name": "Sodeoka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/ja101280p" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "20210309" } }, "mesh": [ { "descriptor": "Antineoplastic Agents", "descriptor_ui": "D000970", "major_topic": false }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Drug Delivery Systems", "descriptor_ui": "D016503", "major_topic": false }, { "descriptor": "Histone Methyltransferases", "descriptor_ui": "D000076983", "major_topic": false }, { "descriptor": "Histone-Lysine N-Methyltransferase", "descriptor_ui": "D011495", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Molecular Structure", "descriptor_ui": "D015394", "major_topic": false }, { "descriptor": "Piperazines", "descriptor_ui": "D010879", "major_topic": false }, { "descriptor": "Structure-Activity Relationship", "descriptor_ui": "D013329", "major_topic": false } ], "publication": { "conference_name": null, "date": "2010 Mar 31", "date_precision": "day", "issue": "12", "normalized_date": "2010-03-31", "pages": "4078-4079", "proceedings_title": null, "publisher": "", "title": "Journal of the American Chemical Society", "volume": "132", "year": 2010 }, "ssbd": { "database": [], "repository": [] }, "title": "Total synthesis of (+)-chaetocin and its analogues: their histone methyltransferase G9a inhibitory activity.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "A highly efficient, catalytic, diastereo- and enantioselective conjugate addition of alpha-ketoesters to nitroalkenes has been devised. The reaction was applicable to various substrates. Notably, the combination of endogenous and exogenous bases was effective, allowing a small amount of the catalyst (0.1-1 mol % Ni) to promote the reaction efficiently. The synthetic utility of this reaction was demonstrated in the synthesis of substituted pyrrolidine derivatives, whose stereochemistry is closely related to biologically important natural products such as kainic acid.", "classifications": [ { "id": "Sodeoka", "label": "Group Sodeoka", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Ayako", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Sylvain", "last_name": "Lectard", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Hashizume", "name": null }, { "creator_type": "author", "first_name": "Yoshitaka", "last_name": "Hamashima", "name": null }, { "creator_type": "author", "first_name": "Mikiko", "last_name": "Sodeoka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/ja909457b" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "20199025" } }, "mesh": [ { "descriptor": "Acetates", "descriptor_ui": "D000085", "major_topic": false }, { "descriptor": "Alkenes", "descriptor_ui": "D000475", "major_topic": false }, { "descriptor": "Catalysis", "descriptor_ui": "D002384", "major_topic": false }, { "descriptor": "Esters", "descriptor_ui": "D004952", "major_topic": false }, { "descriptor": "Ketones", "descriptor_ui": "D007659", "major_topic": false }, { "descriptor": "Molecular Structure", "descriptor_ui": "D015394", "major_topic": false }, { "descriptor": "Nickel", "descriptor_ui": "D009532", "major_topic": false }, { "descriptor": "Nitro Compounds", "descriptor_ui": "D009574", "major_topic": false }, { "descriptor": "Stereoisomerism", "descriptor_ui": "D013237", "major_topic": false } ], "publication": { "conference_name": null, "date": "2010 Mar 31", "date_precision": "day", "issue": "12", "normalized_date": "2010-03-31", "pages": "4036-4037", "proceedings_title": null, "publisher": "", "title": "Journal of the American Chemical Society", "volume": "132", "year": 2010 }, "ssbd": { "database": [], "repository": [] }, "title": "Diastereo- and enantioselective conjugate addition of alpha-ketoesters to nitroalkenes catalyzed by a chiral Ni(OAc)(2) complex under mild conditions.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Ca2+ signaling mediated by phospholipase C that produces inositol 1,4,5-trisphosphate [Ins(1,4,5)P3] and diacylglycerol (DAG) controls lymphocyte activation. In contrast to store-operated Ca2+ entry activated by Ins(1,4,5)P3-induced Ca2+ release from endoplasmic reticulum, the importance of DAG-activated Ca2+ entry remains elusive. Here, we describe the physiological role of DAG-activated Ca2+ entry channels in B-cell receptor (BCR) signaling. In avian DT40 B cells, deficiency of transient receptor potential TRPC3 at the plasma membrane (PM) impaired DAG-activated cation currents and, upon BCR stimulation, the sustained translocation to the PM of protein kinase Cβ (PKCβ) that activated extracellular signal-regulated kinase (ERK). Notably, TRPC3 showed direct association with PKCβ that maintained localization of PKCβ at the PM. Thus, TRPC3 functions as both a Ca2+-permeable channel and a protein scaffold at the PM for downstream PKCβ activation in B cells.", "classifications": [ { "id": "Nishida", "label": "Group Nishida", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Takuro", "last_name": "Numaga", "name": null }, { "creator_type": "author", "first_name": "Motohiro", "last_name": "Nishida", "name": null }, { "creator_type": "author", "first_name": "Shigeki", "last_name": "Kiyonaka", "name": null }, { "creator_type": "author", "first_name": "Kenta", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Katano", "name": null }, { "creator_type": "author", "first_name": "Emiko", "last_name": "Mori", "name": null }, { "creator_type": "author", "first_name": "Tomohiro", "last_name": "Kurosaki", "name": null }, { "creator_type": "author", "first_name": "Ryuji", "last_name": "Inoue", "name": null }, { "creator_type": "author", "first_name": "Masaki", "last_name": "Hikida", "name": null }, { "creator_type": "author", "first_name": "James W.", "last_name": "Putney", "name": null }, { "creator_type": "author", "first_name": "Yasuo", "last_name": "Mori", "name": null } ], "identifiers": { "doi": { "normalized": "10.1242/jcs.061051" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "20179100" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "B-Lymphocytes", "descriptor_ui": "D001402", "major_topic": false }, { "descriptor": "Calcium Channels", "descriptor_ui": "D015220", "major_topic": false }, { "descriptor": "Calcium Signaling", "descriptor_ui": "D020013", "major_topic": true }, { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "Cell Membrane", "descriptor_ui": "D002462", "major_topic": false }, { "descriptor": "Chickens", "descriptor_ui": "D002645", "major_topic": false }, { "descriptor": "Diglycerides", "descriptor_ui": "D004075", "major_topic": false }, { "descriptor": "Enzyme Activation", "descriptor_ui": "D004789", "major_topic": false }, { "descriptor": "Extracellular Signal-Regulated MAP Kinases", "descriptor_ui": "D048049", "major_topic": false }, { "descriptor": "HeLa Cells", "descriptor_ui": "D006367", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Ion Channel Gating", "descriptor_ui": "D015640", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Models, Biological", "descriptor_ui": "D008954", "major_topic": false }, { "descriptor": "NFATC Transcription Factors", "descriptor_ui": "D050778", "major_topic": false }, { "descriptor": "Protein Binding", "descriptor_ui": "D011485", "major_topic": false }, { "descriptor": "Protein Kinase C", "descriptor_ui": "D011493", "major_topic": false }, { "descriptor": "Protein Kinase C beta", "descriptor_ui": "D064546", "major_topic": false }, { "descriptor": "Protein Transport", "descriptor_ui": "D021381", "major_topic": false }, { "descriptor": "Receptors, Antigen, B-Cell", "descriptor_ui": "D011947", "major_topic": false }, { "descriptor": "TRPC Cation Channels", "descriptor_ui": "D050052", "major_topic": false } ], "publication": { "conference_name": null, "date": "2010 Mar 15", "date_precision": "day", "issue": "6", "normalized_date": "2010-03-15", "pages": "927-938", "proceedings_title": null, "publisher": "", "title": "Journal of Cell Science", "volume": "123", "year": 2010 }, "ssbd": { "database": [], "repository": [] }, "title": "Ca2+ influx and protein scaffolding via TRPC3 sustain PKCβ and ERK activation in B cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: Although an increasing number of histone demethylases have been identified and biochemically characterized, their biological functions largely remain uncharacterized, particularly in the context of human diseases such as cancer. We investigated the role of KDM5B, a JmjC histone demethylase, in human carcinogenesis. Quantitative RT-PCR and microarray analyses were used to examine the expression profiles of histone demethylases in clinical tissue samples. We also examined the functional effects of KDM5B on the growth of cancer cell lines treated with small interfering RNAs (siRNAs). Downstream genes and signal cascades induced by KDM5B expression were identified from Affymetrix Gene Chip experiments, and validated by real-time PCR and reporter assays. Cell cycle-dependent characteristics of KDM5B were identified by immunofluorescence and FACS. RESULTS: Quantitative RT-PCR analysis confirmed that expression levels of KDM5B are significantly higher in human bladder cancer tissues than in their corresponding non-neoplastic bladder tissues (P < 0.0001). The expression profile analysis of clinical tissues also revealed up-regulation of KDM5B in various kinds of malignancies. Transfection of KDM5B-specific siRNA into various bladder and lung cancer cell lines significantly suppressed the proliferation of cancer cells and increased the number of cells in sub-G1 phase. Microarray expression analysis indicated that E2F1 and E2F2 are downstream genes in the KDM5B pathway. CONCLUSIONS: Inhibition of KDM5B may affect apoptosis and reduce growth of cancer cells. Further studies will explore the pan-cancer therapeutic potential of KDM5B inhibition.", "classifications": [ { "id": "Hamamoto", "label": "Group Hamamoto", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Shinya", "last_name": "Hayami", "name": null }, { "creator_type": "author", "first_name": "Masanori", "last_name": "Yoshimatsu", "name": null }, { "creator_type": "author", "first_name": "Abhimanyu", "last_name": "Veerakumarasivam", "name": null }, { "creator_type": "author", "first_name": "Motoko", "last_name": "Unoki", "name": null }, { "creator_type": "author", "first_name": "Yukiko", "last_name": "Iwai", "name": null }, { "creator_type": "author", "first_name": "Tatsuhiko", "last_name": "Tsunoda", "name": null }, { "creator_type": "author", "first_name": "Helen I.", "last_name": "Field", "name": null }, { "creator_type": "author", "first_name": "John D.", "last_name": "Kelly", "name": null }, { "creator_type": "author", "first_name": "David E.", "last_name": "Neal", "name": null }, { "creator_type": "author", "first_name": "Hiroki", "last_name": "Yamaue", "name": null }, { "creator_type": "author", "first_name": "Bruce A. J.", "last_name": "Ponder", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Ryuji", "last_name": "Hamamoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1186/1476-4598-9-59" }, "pmcid": { "normalized": "PMC2848192" }, "pmid": { "normalized": "20226085" } }, "mesh": [ { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Cell Proliferation", "descriptor_ui": "D049109", "major_topic": false }, { "descriptor": "E2F1 Transcription Factor", "descriptor_ui": "D050687", "major_topic": false }, { "descriptor": "E2F2 Transcription Factor", "descriptor_ui": "D050703", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Gene Expression Regulation, Neoplastic", "descriptor_ui": "D015972", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Jumonji Domain-Containing Histone Demethylases", "descriptor_ui": "D056484", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Nuclear Proteins", "descriptor_ui": "D009687", "major_topic": false }, { "descriptor": "Oligonucleotide Array Sequence Analysis", "descriptor_ui": "D020411", "major_topic": false }, { "descriptor": "Precancerous Conditions", "descriptor_ui": "D011230", "major_topic": false }, { "descriptor": "Repressor Proteins", "descriptor_ui": "D012097", "major_topic": false }, { "descriptor": "Reproducibility of Results", "descriptor_ui": "D015203", "major_topic": false }, { "descriptor": "Retinoblastoma Protein", "descriptor_ui": "D016160", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Tissue Array Analysis", "descriptor_ui": "D046888", "major_topic": false }, { "descriptor": "Up-Regulation", "descriptor_ui": "D015854", "major_topic": false } ], "publication": { "conference_name": null, "date": "2010 Mar 13", "date_precision": "day", "issue": "", "normalized_date": "2010-03-13", "pages": "59", "proceedings_title": null, "publisher": "", "title": "Molecular cancer", "volume": "9", "year": 2010 }, "ssbd": { "database": [], "repository": [] }, "title": "Overexpression of the JmjC histone demethylase KDM5B in human carcinogenesis: involvement in the proliferation of cancer cells through the E2F/RB pathway.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Activation of Notch signaling induces the expression of transcriptional repressor genes such as Hes1, leading to repression of proneural gene expression and maintenance of neural stem/progenitor cells. However, a requirement for Notch signaling in the telencephalon was not clear, because in Hes1;Hes3;Hes5 triple-mutant mice, neural stem/progenitor cells are depleted in most regions of the developing CNS, but not in the telencephalon. Here, we investigated a role for Notch signaling in the telencephalon by generating tamoxifen-inducible conditional knock-out mice that lack Rbpj, an intracellular signal mediator of all Notch receptors. When Rbpj was deleted in the embryonic brain, almost all telencephalic neural stem/progenitor cells prematurely differentiated into neurons and were depleted. When Rbpj was deleted in the adult brain, all neural stem cells differentiated into transit-amplifying cells and neurons. As a result, neurogenesis increased transiently, but 3 months later all neural stem cells were depleted and neurogenesis was totally lost. These results indicated an absolute requirement of Notch signaling for the maintenance of neural stem cells and a proper control of neurogenesis in both embryonic and adult brains.", "classifications": [ { "id": "Imayoshi", "label": "Group Imayoshi", "parent": "Imayoshi", "type": "group" }, { "id": "Imayoshi", "label": "Team Imayoshi", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Itaru", "last_name": "Imayoshi", "name": null }, { "creator_type": "author", "first_name": "Masayuki", "last_name": "Sakamoto", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Yamaguchi", "name": null }, { "creator_type": "author", "first_name": "Kensaku", "last_name": "Mori", "name": null }, { "creator_type": "author", "first_name": "Ryoichiro", "last_name": "Kageyama", "name": null } ], "identifiers": { "doi": { "normalized": "10.1523/jneurosci.4987-09.2010" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "20203209" } }, "mesh": [ { "descriptor": "Aging", "descriptor_ui": "D000375", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Count", "descriptor_ui": "D002452", "major_topic": false }, { "descriptor": "Cell Proliferation", "descriptor_ui": "D049109", "major_topic": false }, { "descriptor": "Gene Expression Regulation, Developmental", "descriptor_ui": "D018507", "major_topic": false }, { "descriptor": "Immunoglobulin J Recombination Signal Sequence-Binding Protein", "descriptor_ui": "D051819", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Mice, Transgenic", "descriptor_ui": "D008822", "major_topic": false }, { "descriptor": "Nerve Regeneration", "descriptor_ui": "D009416", "major_topic": false }, { "descriptor": "Neurogenesis", "descriptor_ui": "D055495", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Neurotoxins", "descriptor_ui": "D009498", "major_topic": false }, { "descriptor": "Receptors, Notch", "descriptor_ui": "D051880", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Stem Cells", "descriptor_ui": "D013234", "major_topic": false }, { "descriptor": "Telencephalon", "descriptor_ui": "D013687", "major_topic": false } ], "publication": { "conference_name": null, "date": "2010 Mar 3", "date_precision": "day", "issue": "9", "normalized_date": "2010-03-03", "pages": "3489-3498", "proceedings_title": null, "publisher": "", "title": "The Journal of Neuroscience", "volume": "30", "year": 2010 }, "ssbd": { "database": [], "repository": [] }, "title": "Essential Roles of Notch Signaling in Maintenance of Neural Stem Cells in Developing and Adult Brains.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "We have developed a regulator-free device that enables long-term incubation of mammalian cells for epi-fluorescence imaging, based on a concept that the size of sample to be gassed and heated is reduced to observation scale. A poly(dimethylsiloxane) block stamped on a coverslip works as a long-lasting supplier of CO(2)-rich gas to adjust bicarbonate-containing medium in a tiny chamber at physiological pH, and an oil-immersion objective warms cells across the coverslip. A time-lapse imaging experiment using HeLa cells stably expressing fluorescent cell-cycle indicators showed that the cells in the chamber proliferated with normal cell-cycle period over 2 days.", "classifications": [ { "id": "Sawano", "label": "Group Sawano", "parent": "Shintaku", "type": "group" }, { "id": "Shintaku", "label": "Team Shintaku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Masahiko", "last_name": "Hirano", "name": null }, { "creator_type": "author", "first_name": "Tetsushi", "last_name": "Hoshida", "name": null }, { "creator_type": "author", "first_name": "Asako", "last_name": "Sakaue-Sawano", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Miyawaki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.bbrc.2009.12.181" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "20059969" } }, "mesh": [ { "descriptor": "Cell Cycle", "descriptor_ui": "D002453", "major_topic": false }, { "descriptor": "Dimethylpolysiloxanes", "descriptor_ui": "D004129", "major_topic": false }, { "descriptor": "HeLa Cells", "descriptor_ui": "D006367", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Microscopy, Fluorescence", "descriptor_ui": "D008856", "major_topic": false } ], "publication": { "conference_name": null, "date": "2010 Feb 12", "date_precision": "day", "issue": "3", "normalized_date": "2010-02-12", "pages": "307-310", "proceedings_title": null, "publisher": "", "title": "Biochemical and biophysical research communications", "volume": "392", "year": 2010 }, "ssbd": { "database": [], "repository": [] }, "title": "A poly(dimethylsiloxane)-based device enabling time-lapse imaging with high spatial resolution.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: Continuous NGF stimulation induces PC12 cell differentiation. However, why continuous NGF stimulation is required for differentiation is unclear. In this study, we investigated the underlying mechanisms of the timing-dependent requirement of NGF action for cell differentiation. METHODOLOGY/PRINCIPAL FINDINGS: To address the timing-dependency of the NGF action, we performed a discontinuous stimulation assay consisting of a first transient stimulation followed by an interval and then a second sustained stimulation and quantified the neurite extension level. Consequently, we observed a timing-dependent action of NGF on cell differentiation, and discontinuous NGF stimulation similarly induced differentiation. The first stimulation did not induce neurite extension, whereas the second stimulation induced fast neurite extension; therefore, the first stimulation is likely required as a prerequisite condition. These observations indicate that the action of NGF can be divided into two processes: an initial stimulation-driven latent process and a second stimulation-driven extension process. The latent process appears to require the activities of ERK and transcription, but not PI3K, whereas the extension-process requires the activities of ERK and PI3K, but not transcription. We also found that during the first stimulation, the activity of NGF can be replaced by PACAP, but not by insulin, EGF, bFGF or forskolin; during the second stimulation, however, the activity of NGF cannot be replaced by any of these stimulants. These findings allowed us to identify potential genes specifically involved in the latent process, rather than in other processes, using a microarray. CONCLUSIONS/SIGNIFICANCE: These results demonstrate that NGF induces the differentiation of PC12 cells via mechanically distinct processes: an ERK-driven and transcription-dependent latent process, and an ERK- and PI3K-driven and transcription-independent extension process.", "classifications": [ { "id": "Kuroda", "label": "Group Kuroda", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Jaehoon", "last_name": "Chung", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Kubota", "name": null }, { "creator_type": "author", "first_name": "Yu-ichi", "last_name": "Ozaki", "name": null }, { "creator_type": "author", "first_name": "Shinsuke", "last_name": "Uda", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Kuroda", "name": null } ], "identifiers": { "doi": { "normalized": "10.1371/journal.pone.0009011" }, "pmcid": { "normalized": "PMC2814856" }, "pmid": { "normalized": "20126402" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Dose-Response Relationship, Drug", "descriptor_ui": "D004305", "major_topic": false }, { "descriptor": "Extracellular Signal-Regulated MAP Kinases", "descriptor_ui": "D048049", "major_topic": false }, { "descriptor": "Gene Expression Profiling", "descriptor_ui": "D020869", "major_topic": false }, { "descriptor": "Immunoblotting", "descriptor_ui": "D015151", "major_topic": false }, { "descriptor": "Nerve Growth Factor", "descriptor_ui": "D020932", "major_topic": false }, { "descriptor": "Neurites", "descriptor_ui": "D016501", "major_topic": false }, { "descriptor": "Oligonucleotide Array Sequence Analysis", "descriptor_ui": "D020411", "major_topic": false }, { "descriptor": "PC12 Cells", "descriptor_ui": "D016716", "major_topic": false }, { "descriptor": "Phosphatidylinositol 3-Kinases", "descriptor_ui": "D019869", "major_topic": false }, { "descriptor": "Pituitary Adenylate Cyclase-Activating Polypeptide", "descriptor_ui": "D051219", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Reverse Transcriptase Polymerase Chain Reaction", "descriptor_ui": "D020133", "major_topic": false }, { "descriptor": "Time Factors", "descriptor_ui": "D013997", "major_topic": false }, { "descriptor": "Transcription, Genetic", "descriptor_ui": "D014158", "major_topic": false } ], "publication": { "conference_name": null, "date": "2010 Feb 2", "date_precision": "day", "issue": "2", "normalized_date": "2010-02-02", "pages": "e9011", "proceedings_title": null, "publisher": "", "title": "PloS one", "volume": "5", "year": 2010 }, "ssbd": { "database": [], "repository": [] }, "title": "Timing-dependent actions of NGF required for cell differentiation.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "PURPOSE: Germ line polymorphisms may confer susceptibility to lung cancer in never smokers, but studies in the United States have been limited by the low number of cases seen at single institutions. We hypothesized that we could use the Internet to bolster the accrual of appropriate patients. EXPERIMENTAL DESIGN: We established an Internet-based protocol to collect blood and information from patients throughout the United States. To illustrate the power of this approach, we used these samples, plus additional cases and age-matched controls from the Memorial Sloan-Kettering Cancer Center (New York, NY) and the Aichi Cancer Center (Nagoya, Japan), to analyze germ line DNA for genetic variants reportedly associated with lung cancer susceptibility. The genotypes for the polymorphisms rs763317 (intron 1) and T790M (exon 20) in the EGFR gene were determined by direct sequencing, and CHRNA3 nicotinic acetylcholine receptor single nucleotide polymorphisms (rs8034191 and rs1051730) were genotyped as part of a pilot genome-wide association study. RESULTS: We successfully analyzed germ line DNA from 369 cases, including 45 obtained via the Internet, and 342 controls. A germ line EGFR T790M variant was identified in 2 of the 369 cases (0.54%; 95% confidence interval, 0.21-1.29%), and in none of the 292 controls (P = 0.21). No difference was observed in EGFR rs763317 frequency between cases and controls. Similarly, neither CHRNA3 rs8034191 nor rs1051730 were associated with lung cancer risk. CONCLUSIONS: The Internet provides a way to recruit patients throughout the country for minimal risk studies. This approach could be used to facilitate studies of germ line polymorphisms in specific groups of patients with cancer.", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Nicolas", "last_name": "Girard", "name": null }, { "creator_type": "author", "first_name": "Emil", "last_name": "Lou", "name": null }, { "creator_type": "author", "first_name": "Christopher G.", "last_name": "Azzoli", "name": null }, { "creator_type": "author", "first_name": "Rekha", "last_name": "Reddy", "name": null }, { "creator_type": "author", "first_name": "Mark", "last_name": "Robson", "name": null }, { "creator_type": "author", "first_name": "Megan", "last_name": "Harlan", "name": null }, { "creator_type": "author", "first_name": "Irene", "last_name": "Orlow", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null }, { "creator_type": "author", "first_name": "Khedoudja", "last_name": "Nafa", "name": null }, { "creator_type": "author", "first_name": "Marc", "last_name": "Ladanyi", "name": null }, { "creator_type": "author", "first_name": "Agnes", "last_name": "Viale", "name": null }, { "creator_type": "author", "first_name": "Mark G.", "last_name": "Kris", "name": null }, { "creator_type": "author", "first_name": "Gregory", "last_name": "Riely", "name": null }, { "creator_type": "author", "first_name": "Vincent", "last_name": "Miller", "name": null }, { "creator_type": "author", "first_name": "Robert J.", "last_name": "Klein", "name": null }, { "creator_type": "author", "first_name": "Keitaro", "last_name": "Matsuo", "name": null }, { "creator_type": "author", "first_name": "William", "last_name": "Pao", "name": null } ], "identifiers": { "doi": { "normalized": "10.1158/1078-0432.ccr-09-2437" }, "pmcid": { "normalized": "PMC2808124" }, "pmid": { "normalized": "20068085" } }, "mesh": [ { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Algorithms", "descriptor_ui": "D000465", "major_topic": false }, { "descriptor": "Blood Specimen Collection", "descriptor_ui": "D001800", "major_topic": false }, { "descriptor": "Carcinoma, Non-Small-Cell Lung", "descriptor_ui": "D002289", "major_topic": false }, { "descriptor": "Case-Control Studies", "descriptor_ui": "D016022", "major_topic": false }, { "descriptor": "DNA Mutational Analysis", "descriptor_ui": "D004252", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Gene Frequency", "descriptor_ui": "D005787", "major_topic": false }, { "descriptor": "Genes, erbB-1", "descriptor_ui": "D018773", "major_topic": false }, { "descriptor": "Geography", "descriptor_ui": "D005843", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Internet", "descriptor_ui": "D020407", "major_topic": true }, { "descriptor": "Lung Neoplasms", "descriptor_ui": "D008175", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Pedigree", "descriptor_ui": "D010375", "major_topic": false }, { "descriptor": "Polymorphism, Single Nucleotide", "descriptor_ui": "D020641", "major_topic": true }, { "descriptor": "Retrospective Studies", "descriptor_ui": "D012189", "major_topic": false }, { "descriptor": "Smoking", "descriptor_ui": "D012907", "major_topic": false }, { "descriptor": "United States", "descriptor_ui": "D014481", "major_topic": false } ], "publication": { "conference_name": null, "date": "2010 Jan 15", "date_precision": "day", "issue": "2", "normalized_date": "2010-01-15", "pages": "755-763", "proceedings_title": null, "publisher": "", "title": "Clinical cancer research : an official journal of the American Association for Cancer Research", "volume": "16", "year": 2010 }, "ssbd": { "database": [], "repository": [] }, "title": "Analysis of genetic variants in never-smokers with lung cancer facilitated by an Internet-based blood collection protocol: a preliminary report.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The aim of this study was to explore the association between taste and metabolite profiles of Japanese refined sake. Nontarget metabolome analysis was conducted using capillary electrophoresis mass spectrometry. Zatsumi, an unpleasant not clear flavor, and sweetness, bitterness, and sourness were graded by four experienced panelists. Regression models based on support vector regression (SVR) were used to estimate the relationships among sensory evaluation scores and quantified metabolites and visualized as a nonlinear relationship between sensory scores and metabolite components. The SVR model was highly accurate and versatile: the correlation coefficients for whole training data, cross-validation, and separated validation data were 0.86, 0.73, and 0.73, respectively, for zatsumi. Other sensory scores were also analyzed and modeled by SVR. The methodology demonstrated here carries great potential for predicting the relevant parameters and quantitative relationships between charged metabolites and sensory evaluation in Japanese refined sake.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Masahiro", "last_name": "Sugimoto", "name": null }, { "creator_type": "author", "first_name": "Toshihiko", "last_name": "Koseki", "name": null }, { "creator_type": "author", "first_name": "Akiyoshi", "last_name": "Hirayama", "name": null }, { "creator_type": "author", "first_name": "Shinobu", "last_name": "Abe", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Sano", "name": null }, { "creator_type": "author", "first_name": "Masaru", "last_name": "Tomita", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/jf903680d" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "19961224" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Japan", "descriptor_ui": "D007564", "major_topic": false }, { "descriptor": "Metabolome", "descriptor_ui": "D055442", "major_topic": true }, { "descriptor": "Smell", "descriptor_ui": "D012903", "major_topic": true }, { "descriptor": "Taste", "descriptor_ui": "D013649", "major_topic": true }, { "descriptor": "Wine", "descriptor_ui": "D014920", "major_topic": false } ], "publication": { "conference_name": null, "date": "2010 Jan 13", "date_precision": "day", "issue": "1", "normalized_date": "2010-01-13", "pages": "374-383", "proceedings_title": null, "publisher": "", "title": "Journal of agricultural and food chemistry", "volume": "58", "year": 2010 }, "ssbd": { "database": [], "repository": [] }, "title": "Correlation between sensory evaluation scores of Japanese sake and metabolome profiles.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The retrorubral field (RRF) contains numerous dopaminergic neurons and projects to the parvicellular reticular formation (RFp) of the medullary and pontomedullary brainstem, where many premotor neurons project to the orofacial motor nuclei. To know how the amygdala affects the RRF-RFp pathway in the rat, we first examined the synaptic organization between the central amygdaloid nucleus (CeA) fibers and the RFp-projecting RRF neurons by using combined anterograde and retrograde tracing techniques. After ipsilateral injections of biotinylated dextran amine (BDA) into the CeA and Fluoro-gold (FG) into the RFp, the prominent overlapping distribution of BDA-labeled axon terminals and FG-labeled neurons was found in the lateral part of the RRF ipsilateral to the injection sites, where the BDA-labeled axon terminals made symmetrical synapses with somata and dendrites of the FG-labeled neurons. Using a combination of retrograde tracing and immunohistochemistry for tyrosine hydroxylase (TH), we secondly demonstrated that the RFp-projecting RRF neurons were immunonegative for TH. Using a combination of anterograde tracing and immunohistochemistry for glutamic acid decarboxylase (GAD), we finally revealed that the CeA axon terminals in the RRF were immunoreactive for GAD. The present results suggest that GABAergic CeA neurons may exert inhibitory influences on non-dopaminergic RRF neurons that project to the RFp in the control of orofacial movements closely related to emotional behavior.", "classifications": [ { "id": "Yokota", "label": "Group Yokota", "parent": "Enomoto", "type": "group" }, { "id": "Enomoto", "label": "Team Enomoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Toshiko", "last_name": "Tsumori", "name": null }, { "creator_type": "author", "first_name": "Yi", "last_name": "Qin", "name": null }, { "creator_type": "author", "first_name": "Shigefumi", "last_name": "Yokota", "name": null }, { "creator_type": "author", "first_name": "Jian-Guo", "last_name": "Niu", "name": null }, { "creator_type": "author", "first_name": "Yukihiko", "last_name": "Yasui", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.brainres.2009.09.118" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "19833110" } }, "mesh": [ { "descriptor": "Amygdala", "descriptor_ui": "D000679", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Axons", "descriptor_ui": "D001369", "major_topic": true }, { "descriptor": "Biotin", "descriptor_ui": "D001710", "major_topic": false }, { "descriptor": "Dendrites", "descriptor_ui": "D003712", "major_topic": false }, { "descriptor": "Dextrans", "descriptor_ui": "D003911", "major_topic": false }, { "descriptor": "Glutamate Decarboxylase", "descriptor_ui": "D005968", "major_topic": false }, { "descriptor": "Immunohistochemistry", "descriptor_ui": "D007150", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Medulla Oblongata", "descriptor_ui": "D008526", "major_topic": false }, { "descriptor": "Microscopy, Electron", "descriptor_ui": "D008854", "major_topic": false }, { "descriptor": "Neural Pathways", "descriptor_ui": "D009434", "major_topic": false }, { "descriptor": "Neuronal Tract-Tracers", "descriptor_ui": "D056325", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Photomicrography", "descriptor_ui": "D010784", "major_topic": false }, { "descriptor": "Presynaptic Terminals", "descriptor_ui": "D017729", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Rats, Wistar", "descriptor_ui": "D017208", "major_topic": false }, { "descriptor": "Stilbamidines", "descriptor_ui": "D013266", "major_topic": false }, { "descriptor": "Synapses", "descriptor_ui": "D013569", "major_topic": false }, { "descriptor": "Tyrosine 3-Monooxygenase", "descriptor_ui": "D014446", "major_topic": false } ], "publication": { "conference_name": null, "date": "2010 Jan 8", "date_precision": "day", "issue": "", "normalized_date": "2010-01-08", "pages": "18-28", "proceedings_title": null, "publisher": "", "title": "Brain research", "volume": "1306", "year": 2010 }, "ssbd": { "database": [], "repository": [] }, "title": "Central amygdaloid axon terminals are in contact with retrorubral field neurons that project to the parvicellular reticular formation of the medulla oblongata in the rat.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Mouse embryonic stem (ES) cells are an attractive model system for investigating mammalian biology. Their relatively stable genome and high amenability to genome modification enables the generation of large-scale mutant libraries, which can be subsequently used for phenotype-driven genetic screens. While retroviral vectors have traditionally been used to generate insertional mutations in ES cells, their severe distribution-bias in the mammalian genome substantially limits genome-wide mutagenesis. The recent development of the DNA transposon piggyBac offers an efficient and highly versatile alternative for achieving more unbiased mutagenesis. Furthermore, heterozygous mutations created by insertional mutagens can be converted in parallel to homozygosity by using Blm-deficient ES cells, allowing genome-wide loss-of-function screens to be conducted. In this chapter, we describe the principles underpinning genetic screens in mouse ES cells with examples of previously successful screens. Protocols are provided for piggyBac transposon-mediated mutagenesis, production of the corresponding homozygous mutants in a Blm-deficient genetic background, and methods for mapping and validation of mutations recovered from screens of such libraries.", "classifications": [ { "id": "Yusa", "label": "Group Yusa", "parent": "Eiraku", "type": "group" }, { "id": "Eiraku", "label": "Team Eiraku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Meng Amy", "last_name": "Li", "name": null }, { "creator_type": "author", "first_name": "Stephen J.", "last_name": "Pettitt", "name": null }, { "creator_type": "author", "first_name": "Kosuke", "last_name": "Yusa", "name": null }, { "creator_type": "author", "first_name": "Allan", "last_name": "Bradley", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/s0076-6879(10)77012-9" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "20699144" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Embryonic Stem Cells", "descriptor_ui": "D053595", "major_topic": false }, { "descriptor": "Genetic Vectors", "descriptor_ui": "D005822", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mutagenesis", "descriptor_ui": "D016296", "major_topic": false } ], "publication": { "conference_name": null, "date": "2010", "date_precision": "year", "issue": "", "normalized_date": "2010", "pages": "217-242", "proceedings_title": null, "publisher": "", "title": "Methods in enzymology", "volume": "477", "year": 2010 }, "ssbd": { "database": [], "repository": [] }, "title": "Genome-wide forward genetic screens in mouse ES cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The synaptic organization between vesicular glutamate transporter 2 (VGLUT2)-immunoreactive (ir) axon terminals and phrenic motoneurons in the neonatal rat was examined using a combined retrograde tracing and immunohistochemistry for VGLUT2. The phrenic nucleus (PhN) contained large numbers of VGLUT2-ir axon terminals, some of which made axosomatic and axodendritic synapses with PhN motoneurons. These terminals were of asymmetrical type and contained spherical clear synaptic vesicles. The results suggest that in the neonatal rat glutamatergic synapses onto PhN motoneurons exist and mediate excitatory transmission to drive PhN motoneurons.", "classifications": [ { "id": "Yokota", "label": "Group Yokota", "parent": "Enomoto", "type": "group" }, { "id": "Enomoto", "label": "Team Enomoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Shigefumi", "last_name": "Yokota", "name": null }, { "creator_type": "author", "first_name": "Yoshio", "last_name": "Shinozaki", "name": null }, { "creator_type": "author", "first_name": "Yoshitaka", "last_name": "Oku", "name": null }, { "creator_type": "author", "first_name": "Yasumasa", "last_name": "Okada", "name": null }, { "creator_type": "author", "first_name": "Yukihiko", "last_name": "Yasui", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/978-1-4419-5692-7_38" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "20217347" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Animals, Newborn", "descriptor_ui": "D000831", "major_topic": false }, { "descriptor": "Axons", "descriptor_ui": "D001369", "major_topic": false }, { "descriptor": "Cholera Toxin", "descriptor_ui": "D002772", "major_topic": false }, { "descriptor": "Immunohistochemistry", "descriptor_ui": "D007150", "major_topic": false }, { "descriptor": "In Vitro Techniques", "descriptor_ui": "D066298", "major_topic": false }, { "descriptor": "Motor Neurons", "descriptor_ui": "D009046", "major_topic": false }, { "descriptor": "Phrenic Nerve", "descriptor_ui": "D010791", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Rats, Wistar", "descriptor_ui": "D017208", "major_topic": false }, { "descriptor": "Synapses", "descriptor_ui": "D013569", "major_topic": false }, { "descriptor": "Vesicular Glutamate Transport Protein 2", "descriptor_ui": "D050599", "major_topic": false } ], "publication": { "conference_name": null, "date": "2010", "date_precision": "year", "issue": "", "normalized_date": "2010", "pages": "189-192", "proceedings_title": null, "publisher": "", "title": "Advances in experimental medicine and biology", "volume": "669", "year": 2010 }, "ssbd": { "database": [], "repository": [] }, "title": "Vesicular glutamate transporter 2-immunoreactive synapses onto phrenic motoneurons in the neonatal rat.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Saliva is a readily accessible and informative biofluid, making it ideal for the early detection of a wide range of diseases including cardiovascular, renal, and autoimmune diseases, viral and bacterial infections and, importantly, cancers. Saliva-based diagnostics, particularly those based on metabolomics technology, are emerging and offer a promising clinical strategy, characterizing the association between salivary analytes and a particular disease. Here, we conducted a comprehensive metabolite analysis of saliva samples obtained from 215 individuals (69 oral, 18 pancreatic and 30 breast cancer patients, 11 periodontal disease patients and 87 healthy controls) using capillary electrophoresis time-of-flight mass spectrometry (CE-TOF-MS). We identified 57 principal metabolites that can be used to accurately predict the probability of being affected by each individual disease. Although small but significant correlations were found between the known patient characteristics and the quantified metabolites, the profiles manifested relatively higher concentrations of most of the metabolites detected in all three cancers in comparison with those in people with periodontal disease and control subjects. This suggests that cancer-specific signatures are embedded in saliva metabolites. Multiple logistic regression models yielded high area under the receiver-operating characteristic curves (AUCs) to discriminate healthy controls from each disease. The AUCs were 0.865 for oral cancer, 0.973 for breast cancer, 0.993 for pancreatic cancer, and 0.969 for periodontal diseases. The accuracy of the models was also high, with cross-validation AUCs of 0.810, 0.881, 0.994, and 0.954, respectively. Quantitative information for these 57 metabolites and their combinations enable us to predict disease susceptibility. These metabolites are promising biomarkers for medical screening.Electronic supplementary material: The online version of this article (doi:10.1007/s11306-009-0178-y) contains supplementary material, which is available to authorized users.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Masahiro", "last_name": "Sugimoto", "name": null }, { "creator_type": "author", "first_name": "David T.", "last_name": "Wong", "name": null }, { "creator_type": "author", "first_name": "Akiyoshi", "last_name": "Hirayama", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Masaru", "last_name": "Tomita", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/s11306-009-0178-y" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "20300169" } }, "mesh": [], "publication": { "conference_name": null, "date": "2010", "date_precision": "year", "issue": "1", "normalized_date": "2010", "pages": "78-95", "proceedings_title": null, "publisher": "", "title": "Metabolomics", "volume": "6", "year": 2010 }, "ssbd": { "database": [], "repository": [] }, "title": "Capillary electrophoresis mass spectrometry-based saliva metabolomics identified oral, breast and pancreatic cancer-specific profiles.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Since most bio-production processes are conducted in a batch or fed-batch manner, the evaluation of metabolism with respect to time is highly desirable. Toward this aim, we applied (13)C-metabolic flux analysis to nonstationary conditions by measuring the mass isotopomer distribution of intracellular metabolites. We performed our analysis on batch cultures of wild-type Escherichia coli, as well as on Pyk and Pgi mutants, obtained the fluxes and metabolite concentrations as a function of time. Our results for the wild-type indicated that the TCA cycle flux tended to increase during growth on glucose. Following glucose exhaustion, cells controlled the branch ratio between the glyoxylate pathway and the TCA cycle, depending on the availability of acetate. In the Pyk mutant, the concentrations of glycolytic intermediates changed drastically over time due to the dumping and feedback inhibition caused by PEP accumulation. Nevertheless, the flux distribution and free amino acid concentrations changed little. The growth rate and the fluxes remained constant in the Pgi mutant and the glucose-6-phosphate dehydrogenase reaction was the rate-limiting step. The measured fluxes were compared with those predicted by flux balance analysis using maximization of biomass yield or ATP production. Our findings indicate that the objective function of biosynthesis became less important as time proceeds on glucose in the wild-type, while it remained highly important in the Pyk mutant. Furthermore, ATP production was the primary objective function in the Pgi mutant. This study demonstrates how cells adjust their metabolism in response to environmental changes and/or genetic perturbations in the batch cultivation.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yoshihiro", "last_name": "Toya", "name": null }, { "creator_type": "author", "first_name": "Nobuyoshi", "last_name": "Ishii", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Nakahigashi", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Hirasawa", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Masaru", "last_name": "Tomita", "name": null }, { "creator_type": "author", "first_name": "Kazuyuki", "last_name": "Shimizu", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/btpr.420" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "20730757" } }, "mesh": [ { "descriptor": "Carbon Isotopes", "descriptor_ui": "D002247", "major_topic": false }, { "descriptor": "Escherichia coli", "descriptor_ui": "D004926", "major_topic": false }, { "descriptor": "Gas Chromatography-Mass Spectrometry", "descriptor_ui": "D008401", "major_topic": false }, { "descriptor": "Gene Knockout Techniques", "descriptor_ui": "D055786", "major_topic": false }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": false } ], "publication": { "conference_name": null, "date": "2010 Jul-Aug", "date_precision": "unknown", "issue": "4", "normalized_date": null, "pages": "975-992", "proceedings_title": null, "publisher": "", "title": "Biotechnology progress", "volume": "26", "year": 2010 }, "ssbd": { "database": [], "repository": [] }, "title": "13C-metabolic flux analysis for batch culture of Escherichia coli and its Pyk and Pgi gene knockout mutants based on mass isotopomer distribution of intracellular metabolites.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "We report here that butyrate, a naturally occurring fatty acid commonly used as a nutritional supplement and differentiation agent, greatly enhances the efficiency of induced pluripotent stem (iPS) cell derivation from human adult or fetal fibroblasts. After transient butyrate treatment, the iPS cell derivation efficiency is enhanced by 15- to 51-fold using either retroviral or piggyBac transposon vectors expressing 4 to 5 reprogramming genes. Butyrate stimulation is more remarkable (>100- to 200-fold) on reprogramming in the absence of either KLF4 or MYC transgene. Butyrate treatment did not negatively affect properties of iPS cell lines established by either 3 or 4 retroviral vectors or a single piggyBac DNA transposon vector. These characterized iPS cell lines, including those derived from an adult patient with sickle cell disease by either the piggyBac or retroviral vectors, show normal karyotypes and pluripotency. To gain insights into the underlying mechanisms of butyrate stimulation, we conducted genome-wide gene expression and promoter DNA methylation microarrays and other epigenetic analyses on established iPS cells and cells from intermediate stages of the reprogramming process. By days 6 to 12 during reprogramming, butyrate treatment enhanced histone H3 acetylation, promoter DNA demethylation, and the expression of endogenous pluripotency-associated genes, including DPPA2, whose overexpression partially substitutes for butyrate stimulation. Thus, butyrate as a cell permeable small molecule provides a simple tool to further investigate molecular mechanisms of cellular reprogramming. Moreover, butyrate stimulation provides an efficient method for reprogramming various human adult somatic cells, including cells from patients that are more refractory to reprogramming.", "classifications": [ { "id": "Yusa", "label": "Group Yusa", "parent": "Eiraku", "type": "group" }, { "id": "Eiraku", "label": "Team Eiraku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Prashant", "last_name": "Mali", "name": null }, { "creator_type": "author", "first_name": "Bin-Kuan", "last_name": "Chou", "name": null }, { "creator_type": "author", "first_name": "Jonathan", "last_name": "Yen", "name": null }, { "creator_type": "author", "first_name": "Zhaohui", "last_name": "Ye", "name": null }, { "creator_type": "author", "first_name": "Jizhong", "last_name": "Zou", "name": null }, { "creator_type": "author", "first_name": "Sarah", "last_name": "Dowey", "name": null }, { "creator_type": "author", "first_name": "Robert A.", "last_name": "Brodsky", "name": null }, { "creator_type": "author", "first_name": "Joyce E.", "last_name": "Ohm", "name": null }, { "creator_type": "author", "first_name": "Wayne", "last_name": "Yu", "name": null }, { "creator_type": "author", "first_name": "Stephen B.", "last_name": "Baylin", "name": null }, { "creator_type": "author", "first_name": "Kosuke", "last_name": "Yusa", "name": null }, { "creator_type": "author", "first_name": "Allan", "last_name": "Bradley", "name": null }, { "creator_type": "author", "first_name": "David J.", "last_name": "Meyers", "name": null }, { "creator_type": "author", "first_name": "Chandrani", "last_name": "Mukherjee", "name": null }, { "creator_type": "author", "first_name": "Philip A.", "last_name": "Cole", "name": null }, { "creator_type": "author", "first_name": "Linzhao", "last_name": "Cheng", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/stem.402" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "20201064" } }, "mesh": [ { "descriptor": "Base Sequence", "descriptor_ui": "D001483", "major_topic": false }, { "descriptor": "Butyrates", "descriptor_ui": "D002087", "major_topic": false }, { "descriptor": "Cell Culture Techniques", "descriptor_ui": "D018929", "major_topic": false }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Cellular Senescence", "descriptor_ui": "D016922", "major_topic": false }, { "descriptor": "DNA Transposable Elements", "descriptor_ui": "D004251", "major_topic": false }, { "descriptor": "Epigenesis, Genetic", "descriptor_ui": "D044127", "major_topic": false }, { "descriptor": "Genetic Vectors", "descriptor_ui": "D005822", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Induced Pluripotent Stem Cells", "descriptor_ui": "D057026", "major_topic": false }, { "descriptor": "Kruppel-Like Factor 4", "descriptor_ui": "D000090062", "major_topic": false }, { "descriptor": "Sequence Alignment", "descriptor_ui": "D016415", "major_topic": false } ], "publication": { "conference_name": null, "date": "2010 Apr", "date_precision": "unknown", "issue": "4", "normalized_date": null, "pages": "713-720", "proceedings_title": null, "publisher": "", "title": "Stem cells (Dayton, Ohio)", "volume": "28", "year": 2010 }, "ssbd": { "database": [], "repository": [] }, "title": "Butyrate Greatly Enhances Derivation of Human Induced Pluripotent Stem Cells by Promoting Epigenetic Remodeling and the Expression of Pluripotency-Associated Genes.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Oxidative stress-induced necrosis plays an important role in ischemia-reperfusion injury, such as stroke and heart attack. Here, we describe the development of selective inhibitors of necrosis, MS-1 and IM-54, as potential cardioprotective agents and biological tools for investigating the molecular mechanisms of cell death. By means of chemical modifications of kinase inhibitor BM I, its affinity for various kinases was successfully removed and a potent and selective inhibitor of necrosis, IM-54, was obtained. IM-54 inhibits necrosis induced by oxidative stress, but not apoptosis induced by anticancer drugs.", "classifications": [ { "id": "Sodeoka", "label": "Group Sodeoka", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Mikiko", "last_name": "Sodeoka", "name": null }, { "creator_type": "author", "first_name": "Kosuke", "last_name": "Dodo", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/tcr.201000031" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "20848666" } }, "mesh": [ { "descriptor": "Cardiotonic Agents", "descriptor_ui": "D002316", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Indoles", "descriptor_ui": "D007211", "major_topic": false }, { "descriptor": "Maleimides", "descriptor_ui": "D008301", "major_topic": false }, { "descriptor": "Necrosis", "descriptor_ui": "D009336", "major_topic": false }, { "descriptor": "Oxidative Stress", "descriptor_ui": "D018384", "major_topic": false }, { "descriptor": "Protein Kinase C", "descriptor_ui": "D011493", "major_topic": false }, { "descriptor": "Protein Kinase Inhibitors", "descriptor_ui": "D047428", "major_topic": false }, { "descriptor": "Pyrroles", "descriptor_ui": "D011758", "major_topic": false }, { "descriptor": "Reperfusion Injury", "descriptor_ui": "D015427", "major_topic": false } ], "publication": { "conference_name": null, "date": "2010 Oct", "date_precision": "unknown", "issue": "5", "normalized_date": null, "pages": "308-314", "proceedings_title": null, "publisher": "", "title": "Chemical record (New York, N.Y.)", "volume": "10", "year": 2010 }, "ssbd": { "database": [], "repository": [] }, "title": "Development of selective inhibitors of necrosis.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Calcium ions (Ca(2)(+)) play an essential role in homeostasis and the activity of cardiovascular cells. Ca(2)(+) influx across the plasma membrane induced by neurohumoral factors or mechanical stress elicits physiologically relevant timing and spatial patterns of Ca(2)(+) signaling, which leads to the activation of various cardiovascular functions, such as muscle contraction, gene expression, and hypertrophic growth of myocytes. A canonical transient receptor potential protein subfamily member, TRPC6, which is activated by diacylglycerol and mechanical stretch, works as an upstream regulator of the Ca(2)(+) signaling pathway required for pathological hypertrophy. We have recently found that the inhibition of cGMP-selective phosphodiesterase 5 (PDE5) suppresses agonist- and mechanical stretch-induced hypertrophy through inhibition of Ca(2)(+) influx in rat cardiomyocytes. The inhibition of PDE5 suppressed the increase in frequency of Ca(2)(+) spikes induced by receptor stimulation or mechanical stretch. Activation of protein kinase G by PDE5 inhibition phosphorylated TRPC6 proteins at Thr(6)(9) and prevented TRPC6-mediated Ca(2)(+) influx. Substitution of Ala for Thr(6)(9) in TRPC6 abolished the antihypertrophic effects of PDE5 inhibition. These results suggest that phosphorylation and functional suppression of TRPC6 underlies the prevention of cardiac hypertrophy by PDE5 inhibition. As TRPC6 proteins are also expressed in vascular smooth muscle cells and reportedly participate in vascular remodeling, TRPC6 blockade may be an effective therapeutic strategy for preventing pathologic cardiovascular remodeling.", "classifications": [ { "id": "Nishida", "label": "Group Nishida", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Motohiro", "last_name": "Nishida", "name": null }, { "creator_type": "author", "first_name": "Shota", "last_name": "Saiki", "name": null }, { "creator_type": "author", "first_name": "Naoyuki", "last_name": "Kitajima", "name": null }, { "creator_type": "author", "first_name": "Michio", "last_name": "Nakaya", "name": null }, { "creator_type": "author", "first_name": "Yoji", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Kurose", "name": null } ], "identifiers": { "doi": { "normalized": "10.1248/yakushi.130.1427" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "21048399" } }, "mesh": [ { "descriptor": "Amino Acid Substitution", "descriptor_ui": "D019943", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Calcium Signaling", "descriptor_ui": "D020013", "major_topic": false }, { "descriptor": "Cardiomegaly", "descriptor_ui": "D006332", "major_topic": false }, { "descriptor": "Cardiovascular Physiological Phenomena", "descriptor_ui": "D002320", "major_topic": true }, { "descriptor": "Cyclic GMP-Dependent Protein Kinases", "descriptor_ui": "D017869", "major_topic": false }, { "descriptor": "Cyclic Nucleotide Phosphodiesterases, Type 5", "descriptor_ui": "D054706", "major_topic": false }, { "descriptor": "Drug Design", "descriptor_ui": "D015195", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Muscle, Smooth, Vascular", "descriptor_ui": "D009131", "major_topic": false }, { "descriptor": "Phosphodiesterase 5 Inhibitors", "descriptor_ui": "D058986", "major_topic": false }, { "descriptor": "Phosphorylation", "descriptor_ui": "D010766", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Stress, Mechanical", "descriptor_ui": "D013314", "major_topic": false }, { "descriptor": "TRPC Cation Channels", "descriptor_ui": "D050052", "major_topic": false }, { "descriptor": "TRPC6 Cation Channel", "descriptor_ui": "D000074287", "major_topic": false } ], "publication": { "conference_name": null, "date": "2010 Nov", "date_precision": "unknown", "issue": "11", "normalized_date": null, "pages": "1427-1433", "proceedings_title": null, "publisher": "", "title": "Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan", "volume": "130", "year": 2010 }, "ssbd": { "database": [], "repository": [] }, "title": "[Regulation of cardiovascular functions by the phosphorylation of TRPC channels].", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Amoebiasis, caused by infection with the enteric protist Entamoeba histolytica, is one of the major parasitic diseases. Although metronidazole and its derivatives are currently employed in therapy, the paucity of effective drugs and potential clinical resistance necessitate the development of a novel drug. Trifluoromethionine (TFM) is a promising lead compound for antiamoebic drugs. To potentiate the antiamoebic effect of TFM, we synthesised various amide derivatives of TFM and evaluated their cytotoxicity. The amide derivatives of TFM were observed to have a superior cytotoxic effect compared with TFM and metronidazole against E. histolytica in vitro. Although TFM showed cytotoxicity following degradation by methionine gamma-lyase, the derivatives were degraded by the enzyme less efficiently compared with TFM. We further demonstrated that a representative derivative was hydrolysed by the amoebic cell lysate to first yield TFM, followed by degradation similar to TFM. Hydrolysis was partially inhibited by protease inhibitors. A single subcutaneous or oral administration of TFM and its amide derivatives also effectively prevented the formation of amoebic liver abscess in a rodent model. These data demonstrate the improved effectiveness of TFM derivatives against E. histolytica infection and elucidate the mechanisms underlining the mode of action of these compounds.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Dan", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Seiki", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Yasui", "name": null }, { "creator_type": "author", "first_name": "Norio", "last_name": "Shibata", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Toru", "name": null }, { "creator_type": "author", "first_name": "Masaichi", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Gensuke", "last_name": "Tokoro", "name": null }, { "creator_type": "author", "first_name": "Vahab", "last_name": "Ali", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Tsutomu", "last_name": "Takeuchi", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Suematsu", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Nozaki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.ijantimicag.2009.08.016" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "19910163" } }, "mesh": [ { "descriptor": "Administration, Oral", "descriptor_ui": "D000284", "major_topic": false }, { "descriptor": "Amides", "descriptor_ui": "D000577", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Antiprotozoal Agents", "descriptor_ui": "D000981", "major_topic": false }, { "descriptor": "Cricetinae", "descriptor_ui": "D006224", "major_topic": false }, { "descriptor": "Cricetulus", "descriptor_ui": "D003412", "major_topic": false }, { "descriptor": "Entamoeba histolytica", "descriptor_ui": "D004748", "major_topic": false }, { "descriptor": "Entamoebiasis", "descriptor_ui": "D004749", "major_topic": false }, { "descriptor": "Inhibitory Concentration 50", "descriptor_ui": "D020128", "major_topic": false }, { "descriptor": "Liver Abscess", "descriptor_ui": "D008100", "major_topic": false }, { "descriptor": "Methionine", "descriptor_ui": "D008715", "major_topic": false }, { "descriptor": "Metronidazole", "descriptor_ui": "D008795", "major_topic": false }, { "descriptor": "Molecular Structure", "descriptor_ui": "D015394", "major_topic": false }, { "descriptor": "Quantitative Structure-Activity Relationship", "descriptor_ui": "D021281", "major_topic": false } ], "publication": { "conference_name": null, "date": "2010 Jan", "date_precision": "unknown", "issue": "1", "normalized_date": null, "pages": "56-61", "proceedings_title": null, "publisher": "", "title": "International journal of antimicrobial agents", "volume": "35", "year": 2010 }, "ssbd": { "database": [], "repository": [] }, "title": "Cytotoxic effect of amide derivatives of trifluoromethionine against the enteric protozoan parasite Entamoeba histolytica.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "CE-TOFMS is a powerful method for profiling charged metabolites. However, the limited availability of metabolite standards hinders the process of identifying compounds from detected features in CE-TOFMS data sets. To overcome this problem, we developed a method to identify unknown peaks based on the predicted migration time (t(m)) and accurate m/z values. We developed a predictive model using 375 standard cationic metabolites and support vector regression. The model yielded good correlations between the predicted and measured t(m) (R=0.952 and 0.905 using complete and cross-validation data sets, respectively). Using the trained model, we subsequently predicted the t(m) for 2938 metabolites available from the public databases and assigned tentative identities to noise-filtered features in human urine samples. While 38.9% of the peaks were assigned metabolite names by matching with the standard library alone, the proportion increased to 52.2%. The proposed methodology increases the value of metabolomic data sets obtained from CE-TOFMS profiling.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Masahiro", "last_name": "Sugimoto", "name": null }, { "creator_type": "author", "first_name": "Akiyoshi", "last_name": "Hirayama", "name": null }, { "creator_type": "author", "first_name": "Martin", "last_name": "Robert", "name": null }, { "creator_type": "author", "first_name": "Shinobu", "last_name": "Abe", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Masaru", "last_name": "Tomita", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/elps.200900584" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "20568260" } }, "mesh": [ { "descriptor": "Databases, Factual", "descriptor_ui": "D016208", "major_topic": false }, { "descriptor": "Electrophoresis, Capillary", "descriptor_ui": "D019075", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mass Spectrometry", "descriptor_ui": "D013058", "major_topic": false }, { "descriptor": "Metabolome", "descriptor_ui": "D055442", "major_topic": false }, { "descriptor": "Metabolomics", "descriptor_ui": "D055432", "major_topic": false }, { "descriptor": "Models, Statistical", "descriptor_ui": "D015233", "major_topic": false }, { "descriptor": "Urine", "descriptor_ui": "D014556", "major_topic": false } ], "publication": { "conference_name": null, "date": "2010 Jul", "date_precision": "unknown", "issue": "14", "normalized_date": null, "pages": "2311-2318", "proceedings_title": null, "publisher": "", "title": "Electrophoresis", "volume": "31", "year": 2010 }, "ssbd": { "database": [], "repository": [] }, "title": "Prediction of metabolite identity from accurate mass, migration time prediction and isotopic pattern information in CE-TOFMS data.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Somatostatin analogues ameliorated many symptoms caused by neuroendocrine tumors (NET), but their antitumor activities are limited especially in non-functioning cases. An overactivation of signaling pathways under receptor tyrosine-kinase (RTK) has been recently demonstrated in some NET patients, but its details have remained largely unknown. Therefore, in this study, we immunolocalized therapeutic factors and evaluated the data to study the clinical significance of the molecules in non-functioning Japanese gastrointestinal NET. Fifty-two NET cases were available for examination in this study and expression of somatostatin receptor (sstr) 1, 2A, 2B, 3 and 5, activated form of mammalian target of rapamycin (mTOR), eukaryotic initiation factor 4-binding protein 1 (4EBP1), ribosomal protein s6 (S6), extracellular signal-regulated kinase (ERK) and insulin-like growth factor 1 receptor (IGF-1R) was evaluated using immunohistochemistry. We then studied the correlation among the immunohistochemical results of the individual cases using hierarchical clustering analysis. Results of clustering analysis demonstrated that NET cases were basically classified into Cluster I and II. Cluster I was associated with higher expression of sstr1, 2B and 3 and Cluster II was characterized by an activation of the PI3K/Akt pathway and IGF-1R and higher proliferative status. Cluster II was further classified into Cluster IIa and IIb. Cluster IIa was associated with higher expression of sstr1 and 5 and higher proliferative status and Cluster IIb was characterized by ERK activation. Hierarchical clustering analysis of immunoreactivity of the therapeutic factors can classify NET cases into three distinctive groups and the medical treatment may be determined according to this novel classification method for non-functioning NET patients.", "classifications": [ { "id": "Suzuki", "label": "Group Suzuki", "parent": "Takekawa", "type": "group" }, { "id": "Takekawa", "label": "Team Takekawa", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Shinya", "last_name": "Iida", "name": null }, { "creator_type": "author", "first_name": "Yasuhiro", "last_name": "Miki", "name": null }, { "creator_type": "author", "first_name": "Katsuhiko", "last_name": "Ono", "name": null }, { "creator_type": "author", "first_name": "Jun-ichi", "last_name": "Akahira", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Kazuyuki", "last_name": "Ishida", "name": null }, { "creator_type": "author", "first_name": "Mika", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Hironobu", "last_name": "Sasano", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/j.1349-7006.2010.01657.x" }, "pmcid": { "normalized": "PMC11159394" }, "pmid": { "normalized": "20682006" } }, "mesh": [ { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Cluster Analysis", "descriptor_ui": "D016000", "major_topic": false }, { "descriptor": "Extracellular Signal-Regulated MAP Kinases", "descriptor_ui": "D048049", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Immunohistochemistry", "descriptor_ui": "D007150", "major_topic": false }, { "descriptor": "Intracellular Signaling Peptides and Proteins", "descriptor_ui": "D047908", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Multivariate Analysis", "descriptor_ui": "D015999", "major_topic": false }, { "descriptor": "Neuroendocrine Tumors", "descriptor_ui": "D018358", "major_topic": false }, { "descriptor": "Protein Serine-Threonine Kinases", "descriptor_ui": "D017346", "major_topic": false }, { "descriptor": "TOR Serine-Threonine Kinases", "descriptor_ui": "D058570", "major_topic": false } ], "publication": { "conference_name": null, "date": "2010 Oct", "date_precision": "unknown", "issue": "10", "normalized_date": null, "pages": "2278-2285", "proceedings_title": null, "publisher": "", "title": "Cancer science", "volume": "101", "year": 2010 }, "ssbd": { "database": [], "repository": [] }, "title": "Novel classification based on immunohistochemistry combined with hierarchical clustering analysis in non-functioning neuroendocrine tumor patients.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "MassBank is the first public repository of mass spectra of small chemical compounds for life sciences (<3000 Da). The database contains 605 electron-ionization mass spectrometry (EI-MS), 137 fast atom bombardment MS and 9276 electrospray ionization (ESI)-MS(n) data of 2337 authentic compounds of metabolites, 11 545 EI-MS and 834 other-MS data of 10,286 volatile natural and synthetic compounds, and 3045 ESI-MS(2) data of 679 synthetic drugs contributed by 16 research groups (January 2010). ESI-MS(2) data were analyzed under nonstandardized, independent experimental conditions. MassBank is a distributed database. Each research group provides data from its own MassBank data servers distributed on the Internet. MassBank users can access either all of the MassBank data or a subset of the data by specifying one or more experimental conditions. In a spectral search to retrieve mass spectra similar to a query mass spectrum, the similarity score is calculated by a weighted cosine correlation in which weighting exponents on peak intensity and the mass-to-charge ratio are optimized to the ESI-MS(2) data. MassBank also provides a merged spectrum for each compound prepared by merging the analyzed ESI-MS(2) data on an identical compound under different collision-induced dissociation conditions. Data merging has significantly improved the precision of the identification of a chemical compound by 21-23% at a similarity score of 0.6. Thus, MassBank is useful for the identification of chemical compounds and the publication of experimental data.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Hisayuki", "last_name": "Horai", "name": null }, { "creator_type": "author", "first_name": "Masanori", "last_name": "Arita", "name": null }, { "creator_type": "author", "first_name": "Shigehiko", "last_name": "Kanaya", "name": null }, { "creator_type": "author", "first_name": "Yoshito", "last_name": "Nihei", "name": null }, { "creator_type": "author", "first_name": "Tasuku", "last_name": "Ikeda", "name": null }, { "creator_type": "author", "first_name": "Kazuhiro", "last_name": "Suwa", "name": null }, { "creator_type": "author", "first_name": "Yuya", "last_name": "Ojima", "name": null }, { "creator_type": "author", "first_name": "Kenichi", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Ken", "last_name": "Aoshima", "name": null }, { "creator_type": "author", "first_name": "Yoshiya", "last_name": "Oda", "name": null }, { "creator_type": "author", "first_name": "Yuji", "last_name": "Kakazu", "name": null }, { "creator_type": "author", "first_name": "Miyako", "last_name": "Kusano", "name": null }, { "creator_type": "author", "first_name": "Takayuki", "last_name": "Tohge", "name": null }, { "creator_type": "author", "first_name": "Fumio", "last_name": "Matsuda", "name": null }, { "creator_type": "author", "first_name": "Yuji", "last_name": "Sawada", "name": null }, { "creator_type": "author", "first_name": "Masami Yokota", "last_name": "Hirai", "name": null }, { "creator_type": "author", "first_name": "Hiroki", "last_name": "Nakanishi", "name": null }, { "creator_type": "author", "first_name": "Kazutaka", "last_name": "Ikeda", "name": null }, { "creator_type": "author", "first_name": "Naoshige", "last_name": "Akimoto", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Maoka", "name": null }, { "creator_type": "author", "first_name": "Hiroki", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Ara", "name": null }, { "creator_type": "author", "first_name": "Nozomu", "last_name": "Sakurai", "name": null }, { "creator_type": "author", "first_name": "Hideyuki", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Shibata", "name": null }, { "creator_type": "author", "first_name": "Steffen", "last_name": "Neumann", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Iida", "name": null }, { "creator_type": "author", "first_name": "Ken", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Kimito", "last_name": "Funatsu", "name": null }, { "creator_type": "author", "first_name": "Fumito", "last_name": "Matsuura", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Ryo", "last_name": "Taguchi", "name": null }, { "creator_type": "author", "first_name": "Kazuki", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Takaaki", "last_name": "Nishioka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/jms.1777" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "20623627" } }, "mesh": [ { "descriptor": "Databases, Factual", "descriptor_ui": "D016208", "major_topic": true }, { "descriptor": "Information Dissemination", "descriptor_ui": "D033181", "major_topic": false }, { "descriptor": "Mass Spectrometry", "descriptor_ui": "D013058", "major_topic": true }, { "descriptor": "Pharmaceutical Preparations", "descriptor_ui": "D004364", "major_topic": false }, { "descriptor": "Spectrometry, Mass, Electrospray Ionization", "descriptor_ui": "D021241", "major_topic": false } ], "publication": { "conference_name": null, "date": "2010 Jul", "date_precision": "unknown", "issue": "7", "normalized_date": null, "pages": "703-714", "proceedings_title": null, "publisher": "", "title": "Journal of mass spectrometry : JMS", "volume": "45", "year": 2010 }, "ssbd": { "database": [], "repository": [] }, "title": "MassBank: a public repository for sharing mass spectral data for life sciences.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Fragments of double-stranded DNA (dsDNA) forming a right-handed helical structure (B-DNA) stimulate cells to produce type I interferons (IFNs). While an adaptor molecule, IFN-β promoter stimulator 1 (IPS-1), mediates dsDNA-induced cellular signaling in human cells, the underlying molecular mechanism is not fully understood. Here, we demonstrate that the extrachromosomal histone H2B mediates innate antiviral immune responses in human cells. H2B physically interacts with IPS-1 through the association with a newly identified adaptor, CIAO (COOH-terminal importin 9-related adaptor organizing histone H2B and IPS-1), to transmit the cellular signaling for dsDNA but not immunostimulatory RNA. Extrachromosomal histone H2B was biologically crucial for cell-autonomous responses to protect against multiplication of DNA viruses but not an RNA virus. Thus, the present findings provide evidence indicating that the extrachromosomal histone H2B is engaged in the signaling pathway initiated by dsDNA to trigger antiviral innate immune responses.", "classifications": [ { "id": "Sawano", "label": "Group Sawano", "parent": "Shintaku", "type": "group" }, { "id": "Shintaku", "label": "Team Shintaku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Kouji", "last_name": "Kobiyama", "name": null }, { "creator_type": "author", "first_name": "Fumihiko", "last_name": "Takeshita", "name": null }, { "creator_type": "author", "first_name": "Nao", "last_name": "Jounai", "name": null }, { "creator_type": "author", "first_name": "Asako", "last_name": "Sakaue-Sawano", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Miyawaki", "name": null }, { "creator_type": "author", "first_name": "Ken J.", "last_name": "Ishii", "name": null }, { "creator_type": "author", "first_name": "Taro", "last_name": "Kawai", "name": null }, { "creator_type": "author", "first_name": "Shin", "last_name": "Sasaki", "name": null }, { "creator_type": "author", "first_name": "Hisashi", "last_name": "Hirano", "name": null }, { "creator_type": "author", "first_name": "Norihisa", "last_name": "Ishii", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Okuda", "name": null }, { "creator_type": "author", "first_name": "Koichi", "last_name": "Suzuki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1128/jvi.01339-09" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "19906922" } }, "mesh": [ { "descriptor": "Adaptor Proteins, Signal Transducing", "descriptor_ui": "D048868", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Antiviral Agents", "descriptor_ui": "D000998", "major_topic": false }, { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "Chlorocebus aethiops", "descriptor_ui": "D002522", "major_topic": false }, { "descriptor": "DNA", "descriptor_ui": "D004247", "major_topic": false }, { "descriptor": "DNA Viruses", "descriptor_ui": "D004267", "major_topic": false }, { "descriptor": "Gene Expression Regulation", "descriptor_ui": "D005786", "major_topic": false }, { "descriptor": "HeLa Cells", "descriptor_ui": "D006367", "major_topic": false }, { "descriptor": "Histones", "descriptor_ui": "D006657", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Immunity, Innate", "descriptor_ui": "D007113", "major_topic": false }, { "descriptor": "Interferon-beta", "descriptor_ui": "D016899", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "NIH 3T3 Cells", "descriptor_ui": "D041681", "major_topic": false }, { "descriptor": "Promoter Regions, Genetic", "descriptor_ui": "D011401", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": true }, { "descriptor": "Vero Cells", "descriptor_ui": "D014709", "major_topic": false } ], "publication": { "conference_name": null, "date": "2010 Jan", "date_precision": "unknown", "issue": "2", "normalized_date": null, "pages": "822-832", "proceedings_title": null, "publisher": "", "title": "Journal of Virology", "volume": "84", "year": 2010 }, "ssbd": { "database": [], "repository": [] }, "title": "Extrachromosomal Histone H2B Mediates Innate Antiviral Immune Responses Induced by Intracellular Double-Stranded DNA ▿†.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "PURPOSE: To evaluate the relationship between the epidermal growth factor receptor (EGFR) mutation status and the effectiveness of gefitinib monotherapy or chemotherapy in patients with advanced non-small cell lung cancer (NSCLC). METHODS: We retrospectively analyzed a cohort of 100 patients with stage IIIB/IV NSCLC screened for two major EGFR mutations (exon 19 deletions and L858R mutation). RESULTS: Forty-six out of 48 EGFR mutation-positive patients (96%) received gefitinib, whereas only 3 out of 52 EGFR mutation-negative patients (6%) received gefitinib. Favorable objective response rates to gefitinib as first- and second-line treatment (87 and 80%, respectively) were observed in EGFR mutation-positive patients. Overall response rate to chemotherapy as first-line treatment did not differ significantly between patients with EGFR mutations and those without mutation (32 vs. 28%, respectively; P = 0.7198). As to first-line treatment, EGFR mutation-positive patients treated with gefitinib experienced significantly longer progression-free survival (PFS) than did patients who received chemotherapy (median survival, 7.8 months vs. 5.1 months, respectively; P = 0.0323). Similarly, as to second-line treatment, EGFR mutation-positive patients treated with gefitinib had significantly longer PFS than did patients who received chemotherapy (median survival, 6.5 months vs. 4.0 months, respectively; P = 0.0048). Patients with EGFR mutations survived longer than those without EGFR mutations after first-line treatment (median, 24.3 vs. 12.6 months, respectively; P = 0.0029). CONCLUSION: EGFR mutation-positive patients benefit from either first- or second-line gefitinib monotherapy. Further large-scale prospective studies to confirm this finding are needed.", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Kimihide", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null }, { "creator_type": "author", "first_name": "Jangchul", "last_name": "Park", "name": null }, { "creator_type": "author", "first_name": "Shizu", "last_name": "Ogawa", "name": null }, { "creator_type": "author", "first_name": "Ji Young", "last_name": "Park", "name": null }, { "creator_type": "author", "first_name": "Junichi", "last_name": "Shimizu", "name": null }, { "creator_type": "author", "first_name": "Yoshitsugu", "last_name": "Horio", "name": null }, { "creator_type": "author", "first_name": "Keitaro", "last_name": "Matsuo", "name": null }, { "creator_type": "author", "first_name": "Tetsuya", "last_name": "Mitsudomi", "name": null }, { "creator_type": "author", "first_name": "Toyoaki", "last_name": "Hida", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/s00432-009-0685-2" }, "pmcid": { "normalized": "PMC11827932" }, "pmid": { "normalized": "19777258" } }, "mesh": [ { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Carcinoma, Non-Small-Cell Lung", "descriptor_ui": "D002289", "major_topic": false }, { "descriptor": "Cohort Studies", "descriptor_ui": "D015331", "major_topic": false }, { "descriptor": "Disease-Free Survival", "descriptor_ui": "D018572", "major_topic": false }, { "descriptor": "ErbB Receptors", "descriptor_ui": "D066246", "major_topic": false }, { "descriptor": "Exons", "descriptor_ui": "D005091", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Gefitinib", "descriptor_ui": "D000077156", "major_topic": false }, { "descriptor": "Genetic Testing", "descriptor_ui": "D005820", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Lung Neoplasms", "descriptor_ui": "D008175", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": true }, { "descriptor": "Neoplasm Staging", "descriptor_ui": "D009367", "major_topic": false }, { "descriptor": "Protein Kinase Inhibitors", "descriptor_ui": "D047428", "major_topic": false }, { "descriptor": "Quinazolines", "descriptor_ui": "D011799", "major_topic": false }, { "descriptor": "Retrospective Studies", "descriptor_ui": "D012189", "major_topic": false } ], "publication": { "conference_name": null, "date": "2010 Apr", "date_precision": "unknown", "issue": "4", "normalized_date": null, "pages": "527-535", "proceedings_title": null, "publisher": "", "title": "Journal of cancer research and clinical oncology", "volume": "136", "year": 2010 }, "ssbd": { "database": [], "repository": [] }, "title": "Clinical outcomes of advanced non-small cell lung cancer patients screened for epidermal growth factor receptor gene mutations.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Activation of Ca(2+) signaling in cardiomyocytes induced by receptor stimulation or mechanical stress has been implicated in the development of cardiac hypertrophy. However, it is still unclear how intracellular Ca(2+) targets specifically decode the alteration of intracellular Ca(2+) concentration ([Ca(2+)](i)) on the background of the rhythmic Ca(2+) increases required for muscle contraction. In excitable cardiomyocytes, changes in the frequency or amplitude of Ca(2+) transients evoked by Ca(2+) influx-induced Ca(2+) release have been suggested to encode signals for induction of hypertrophy, and a partial depolarization of plasma membrane by receptor stimulation will increase the frequency of Ca(2+) oscillations. We found that activation of diacylglycerol (DAG)-responsive canonical transient receptor potential (TRPC) subfamily channels (TRPC3 and TRPC6) mediate membrane depolarization induced by G(q) protein-coupled receptor stimulation. DAG-mediated membrane depolarization through activation of TRPC3/TRPC6 channels increases the frequency of Ca(2+) spikes, leading to activation of calcineurin-dependent signaling pathways. Inhibition of either TRPC3 or TRPC6 completely suppressed agonist-induced hypertrophic responses, suggesting that TRPC3 and TRPC6 form heterotetramer channels. Furthermore, we found that hypertrophic agonists increase the expression of TRPC6 proteins through activation of G(12) family proteins, leading to amplification of DAG-mediated hypertrophic signaling in cardiomyocytes. As heart failure proceeds through cardiac hypertrophy, TRPC3/TRPC6 channels may be a new therapeutic target for heart failure.", "classifications": [ { "id": "Nishida", "label": "Group Nishida", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Motohiro", "last_name": "Nishida", "name": null }, { "creator_type": "author", "first_name": "Kenta", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Michio", "last_name": "Nakaya", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Kurose", "name": null } ], "identifiers": { "doi": { "normalized": "10.1248/yakushi.130.295" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "20190513" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Calcium", "descriptor_ui": "D002118", "major_topic": false }, { "descriptor": "Calcium Signaling", "descriptor_ui": "D020013", "major_topic": false }, { "descriptor": "Cardiomegaly", "descriptor_ui": "D006332", "major_topic": false }, { "descriptor": "Diglycerides", "descriptor_ui": "D004075", "major_topic": true }, { "descriptor": "Drug Design", "descriptor_ui": "D015195", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Receptors, G-Protein-Coupled", "descriptor_ui": "D043562", "major_topic": false }, { "descriptor": "TRPC Cation Channels", "descriptor_ui": "D050052", "major_topic": false }, { "descriptor": "TRPC6 Cation Channel", "descriptor_ui": "D000074287", "major_topic": false } ], "publication": { "conference_name": null, "date": "2010 Mar", "date_precision": "unknown", "issue": "3", "normalized_date": null, "pages": "295-302", "proceedings_title": null, "publisher": "", "title": "Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan", "volume": "130", "year": 2010 }, "ssbd": { "database": [], "repository": [] }, "title": "[Mechanism of cardiac hypertrophy via diacylglycerol-sensitive TRPC channels].", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Metabolome analyses assisted by capillary electrophoresis-mass spectrometry (CE-MS) have allowed us to systematically grasp changes in small molecular metabolites under disease conditions. We applied CE-MS to mine out biomarkers in hepatic ischemia-reperfusion. Rat livers were exposed to ischemia by clamping of the portal inlet followed by reperfusion. Metabolomic profiling revealed that l contents of taurine in liver and plasma were significantly increased. Of interest is an elevation of hypotaurine, collectively suggesting significance of hypotaurine/taurine in post-ischemic responses. Considering the anti-oxidative capacity of hypotaurine, we examined if supplementation of the compound or its precursor amino acids could affect hepatocellular viability and contents of taurine in liver and plasma. Administration of hypotaurine, N-acetylcysteine or methionine upon reperfusion comparablly attenuated the post-ischemic hepatocellular injury but with different metabolomic profiling among groups: rats treated with methionine or N-acetylcysteine but not those treated with hypotaurine, exhibited significant elevation of hepatic lactate generation without notable recovery of the energy charge. Furthermore, the group treated with hypotaurine exhibited elevation of the plasma taurine, suggesting that the exogenously administered compound was utilized as an antioxidant. These results suggest that taurine serves as a surrogate marker for ischemia-reperfusion indicating effectiveness of hypotaurine as an energy-saving hepatoprotective amino acid.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Tadayuki", "last_name": "Sakuragawa", "name": null }, { "creator_type": "author", "first_name": "Takako", "last_name": "Hishiki", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Ueno", "name": null }, { "creator_type": "author", "first_name": "Satsuki", "last_name": "Ikeda", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Ayako", "last_name": "Yachie-Kinoshita", "name": null }, { "creator_type": "author", "first_name": "Mayumi", "last_name": "Kajimura", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Suematsu", "name": null } ], "identifiers": { "doi": { "normalized": "10.3164/jcbn.09-91" }, "pmcid": { "normalized": "PMC2831091" }, "pmid": { "normalized": "20216945" } }, "mesh": [], "publication": { "conference_name": null, "date": "2010 Mar", "date_precision": "unknown", "issue": "2", "normalized_date": null, "pages": "126-134", "proceedings_title": null, "publisher": "", "title": "Journal of clinical biochemistry and nutrition", "volume": "46", "year": 2010 }, "ssbd": { "database": [], "repository": [] }, "title": "Hypotaurine is an Energy-Saving Hepatoprotective Compound against Ischemia-Reperfusion Injury of the Rat Liver.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "MicroRNA (miRNA) is a class of non-coding RNAs that represses expression of target messenger RNAs posttranscriptionally. A growing body of evidence supports their roles in various normal cellular processes, as well as in pathological conditions, such as cancer. We established a functional screening assay that enables high-throughput identification of miRNAs that have a role in cancer phenotypes of interest, via the combination of pooled lentivirus vectors expressing several hundred miRNA precursors and a custom-made microarray. Self versus self-hybridization analysis using pooled polymerase chain reaction products generated highly linear and reproducible results. To test the feasibility of the assay, we focused on miRNAs that control proliferation of pancreatic cancer cells and successfully identified five miRNAs that negatively control cell proliferation, including miRNA-34a that was previously identified as a representative tumor-suppressive miRNA. The results were further validated using lentivirus vectors expressing each of the five miRNAs or synthetic miRNAs. The function-based nature of the assay enabled identification of miRNAs that were strongly linked to cell proliferation, but the relative ease and flexibility of the assay allow for future studies of cancer stem cells, metastasis and other cancer phenotypes of interest.", "classifications": [ { "id": "Okamoto", "label": "Group Okamoto", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Masashi", "last_name": "Izumiya", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Okamoto", "name": null }, { "creator_type": "author", "first_name": "Naoto", "last_name": "Tsuchiya", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Nakagama", "name": null } ], "identifiers": { "doi": { "normalized": "10.1093/carcin/bgq112" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "20525881" } }, "mesh": [ { "descriptor": "Cell Cycle", "descriptor_ui": "D002453", "major_topic": false }, { "descriptor": "Cell Division", "descriptor_ui": "D002455", "major_topic": false }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "DNA Primers", "descriptor_ui": "D017931", "major_topic": false }, { "descriptor": "Flow Cytometry", "descriptor_ui": "D005434", "major_topic": false }, { "descriptor": "Gene Library", "descriptor_ui": "D015723", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Lentivirus", "descriptor_ui": "D016086", "major_topic": false }, { "descriptor": "MicroRNAs", "descriptor_ui": "D035683", "major_topic": false }, { "descriptor": "Neoplasm Metastasis", "descriptor_ui": "D009362", "major_topic": false }, { "descriptor": "Neoplasms", "descriptor_ui": "D009369", "major_topic": false }, { "descriptor": "Oligonucleotide Array Sequence Analysis", "descriptor_ui": "D020411", "major_topic": false }, { "descriptor": "Pancreatic Neoplasms", "descriptor_ui": "D010190", "major_topic": false }, { "descriptor": "Phenotype", "descriptor_ui": "D010641", "major_topic": false }, { "descriptor": "Polymerase Chain Reaction", "descriptor_ui": "D016133", "major_topic": false }, { "descriptor": "Stem Cells", "descriptor_ui": "D013234", "major_topic": false }, { "descriptor": "T-Lymphocytes", "descriptor_ui": "D013601", "major_topic": false } ], "publication": { "conference_name": null, "date": "2010 Aug", "date_precision": "unknown", "issue": "8", "normalized_date": null, "pages": "1354-1359", "proceedings_title": null, "publisher": "", "title": "Carcinogenesis", "volume": "31", "year": 2010 }, "ssbd": { "database": [], "repository": [] }, "title": "Functional screening using a microRNA virus library and microarrays: a new high-throughput assay to identify tumor-suppressive microRNAs.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The development of neuronal class-specific dendrites is a basis for the correct functioning of the nervous system. For instance, tiling of dendritic arbors (complete, but minimum-overlapping innervation of a field) supports uniform reception of input stimuli. Previous studies have attempted to show the molecular and cellular basis of tiling, and it has been argued that the underlying inhibitory interaction between dendrites is realized by contact-dependent retraction and/or by repulsion of dendrites via extracellular branch suppressors. In this study, we showed that the development and regeneration of the tiling pattern could be reproduced by two different mathematical models (the cell compartment model and the end capped-segment model), in both of which dendrite growth is coupled with the dynamics of an extracellular suppressor that is secreted from dendrites. The analysis of the end capped-segment model in three-dimensional space showed that it generated both non-overlapping arbors as well as overlapping dendritic arbors, which patterns are reminiscent of phenotypes of previously reported tiling mutants in vivo. Moreover, the results of our numerical analysis of the 2 models suggest that tiling patterns could be achieved either by a local increase in the concentration of an intracellular branching activator or by a local decrease in the production of a suppressor at branch ends.", "classifications": [ { "id": "Mochizuki", "label": "Group Mochizuki", "parent": "Eiraku", "type": "group" }, { "id": "Eiraku", "label": "Team Eiraku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Kohei", "last_name": "Shimono", "name": null }, { "creator_type": "author", "first_name": "Kaoru", "last_name": "Sugimura", "name": null }, { "creator_type": "author", "first_name": "Mineko", "last_name": "Kengaku", "name": null }, { "creator_type": "author", "first_name": "Tadashi", "last_name": "Uemura", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Mochizuki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/j.1365-2443.2009.01367.x" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "20070856" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Growth Processes", "descriptor_ui": "D048708", "major_topic": true }, { "descriptor": "Computational Biology", "descriptor_ui": "D019295", "major_topic": false }, { "descriptor": "Computer Simulation", "descriptor_ui": "D003198", "major_topic": false }, { "descriptor": "Dendrites", "descriptor_ui": "D003712", "major_topic": false }, { "descriptor": "Extracellular Space", "descriptor_ui": "D005110", "major_topic": false }, { "descriptor": "Image Processing, Computer-Assisted", "descriptor_ui": "D007091", "major_topic": false }, { "descriptor": "Intracellular Space", "descriptor_ui": "D042541", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Models, Biological", "descriptor_ui": "D008954", "major_topic": true }, { "descriptor": "Nerve Tissue Proteins", "descriptor_ui": "D009419", "major_topic": false }, { "descriptor": "Purkinje Cells", "descriptor_ui": "D011689", "major_topic": false } ], "publication": { "conference_name": null, "date": "2010 Feb", "date_precision": "unknown", "issue": "2", "normalized_date": null, "pages": "137-149", "proceedings_title": null, "publisher": "", "title": "Genes to cells : devoted to molecular & cellular mechanisms", "volume": "15", "year": 2010 }, "ssbd": { "database": [], "repository": [] }, "title": "Computational modeling of dendritic tiling by diffusible extracellular suppressor.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Some Japanese exhibit facial flushing after drinking alcohol. Facial flushing was considered to be caused by acetaldehydemia. The concentration of blood acetaldehyde was concerned with the catalytic activity of acetaldehyde dehydrogenase (ALDH). Acetaldehyde dehydrogenase (ALDH)-2 polymorphism (rs671, Glu504Lys) was known to be associated with upper aerodigestive tract (UAT) cancer due to modulation of ALDH2 enzyme activity. It remains controversial whether facial flushing is useful in predicting UAT cancer risk as a surrogate marker of ALDH2 polymorphism. We conducted a case-control study to assess the risk of UAT cancer and facial flushing and ALDH2 polymorphism. Cases and controls were 585 UAT cancer patients and matched 1170 noncancer outpatients of Aichi Cancer Center Hospital. Information on facial flushing and other lifestyle factors was collected via a self-administered questionnaire. Association between facial flushing, polymorphism, and UAT cancer was assessed by odds ratios and 95% confidence intervals by using conditional logistic regression models. The facial flushing had no significant association with UAT cancer, although ALDH2 Lys allele was significantly associated with UAT cancer. No significant interaction between facial flushing and alcohol consumption was observed in this study, whereas ALDH2 Lys allele had significant association with UAT cancer. The misclassification between facial flushing and ALDH2 genotype was observed in 18% of controls with ALDH2 Glu/Glu genotype and in 16% of controls with ALDH2 Glu/Lys genotype. Facial flushing was less useful to predict UAT cancer risk than genotyping ALDH2 polymorphism.", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Isao", "last_name": "Oze", "name": null }, { "creator_type": "author", "first_name": "Keitaro", "last_name": "Matsuo", "name": null }, { "creator_type": "author", "first_name": "Satoyo", "last_name": "Hosono", "name": null }, { "creator_type": "author", "first_name": "Hidemi", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Takakazu", "last_name": "Kawase", "name": null }, { "creator_type": "author", "first_name": "Miki", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Shunzo", "last_name": "Hatooka", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null }, { "creator_type": "author", "first_name": "Yasuhisa", "last_name": "Hasegawa", "name": null }, { "creator_type": "author", "first_name": "Masayuki", "last_name": "Shinoda", "name": null }, { "creator_type": "author", "first_name": "Kazuo", "last_name": "Tajima", "name": null }, { "creator_type": "author", "first_name": "Hideo", "last_name": "Tanaka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/j.1349-7006.2010.01599.x" }, "pmcid": { "normalized": "PMC11159847" }, "pmid": { "normalized": "20518787" } }, "mesh": [ { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Alcohol Drinking", "descriptor_ui": "D000428", "major_topic": true }, { "descriptor": "Aldehyde Dehydrogenase", "descriptor_ui": "D000444", "major_topic": false }, { "descriptor": "Aldehyde Dehydrogenase, Mitochondrial", "descriptor_ui": "D000071396", "major_topic": false }, { "descriptor": "Esophageal Neoplasms", "descriptor_ui": "D004938", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Flushing", "descriptor_ui": "D005483", "major_topic": false }, { "descriptor": "Genetic Predisposition to Disease", "descriptor_ui": "D020022", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Laryngeal Neoplasms", "descriptor_ui": "D007822", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Mouth Neoplasms", "descriptor_ui": "D009062", "major_topic": false }, { "descriptor": "Pharyngeal Neoplasms", "descriptor_ui": "D010610", "major_topic": false }, { "descriptor": "Polymorphism, Genetic", "descriptor_ui": "D011110", "major_topic": true }, { "descriptor": "Risk", "descriptor_ui": "D012306", "major_topic": false } ], "publication": { "conference_name": null, "date": "2010 Aug", "date_precision": "unknown", "issue": "8", "normalized_date": null, "pages": "1875-1880", "proceedings_title": null, "publisher": "", "title": "Cancer science", "volume": "101", "year": 2010 }, "ssbd": { "database": [], "repository": [] }, "title": "Comparison between self-reported facial flushing after alcohol consumption and ALDH2 Glu504Lys polymorphism for risk of upper aerodigestive tract cancer in a Japanese population.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Despite the widespread availability of genome sequences and the systematic assignment of individual open reading frames, many of the activities of metabolic enzymes are still veiled. It is difficult to assign biochemical functions to enzymes and uncover the in vivo regulation of their enzymatic activities, but this is crucial to understand cellular functions. The development of metabolomics and metabolite profiling, which can globally analyze intracellular and extracellular metabolites, has provided some valuable tools for systems biology. This report reviews the recent metabolomics approaches to elucidate unidentified metabolic systems while focusing on their enzymatic activities, including their biochemical and biological functions, and their regulation in response to environmental perturbations in microorganisms.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Natsumi", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Yoshiaki", "last_name": "Ohashi", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Masaru", "last_name": "Tomita", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.mib.2010.04.006" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "20430690" } }, "mesh": [ { "descriptor": "Energy Metabolism", "descriptor_ui": "D004734", "major_topic": true }, { "descriptor": "Escherichia coli", "descriptor_ui": "D004926", "major_topic": false }, { "descriptor": "Gene Expression Regulation", "descriptor_ui": "D005786", "major_topic": false }, { "descriptor": "Metabolic Networks and Pathways", "descriptor_ui": "D053858", "major_topic": true }, { "descriptor": "Metabolome", "descriptor_ui": "D055442", "major_topic": true }, { "descriptor": "Metabolomics", "descriptor_ui": "D055432", "major_topic": false }, { "descriptor": "Stress, Physiological", "descriptor_ui": "D013312", "major_topic": false }, { "descriptor": "Systems Biology", "descriptor_ui": "D049490", "major_topic": false } ], "publication": { "conference_name": null, "date": "2010 Jun", "date_precision": "unknown", "issue": "3", "normalized_date": null, "pages": "358-362", "proceedings_title": null, "publisher": "", "title": "Current opinion in microbiology", "volume": "13", "year": 2010 }, "ssbd": { "database": [], "repository": [] }, "title": "Unveiling cellular biochemical reactions via metabolomics-driven approaches.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "By exploiting the cell-cycle-dependent proteolysis of two ubiquitination oscillators, human Cdt1 and geminin, which are the direct substrates of SCFSkp2 and APCCdh1 complexes, respectively, Fucci technique labels mammalian cell nuclei in G1 and S/G2/M phases with different colors. Transgenic mice expressing these G1 and S/G2/M markers offer a powerful means to investigate the coordination of the cell cycle with morphogenetic processes. We attempted to introduce these markers into zebrafish embryos to take advantage of their favorable optical properties. However, although the fundamental mechanisms for cell-cycle control appear to be well conserved among species, the G1 marker based on the SCFSkp2-mediated degradation of human Cdt1 did not work in fish cells, probably because the marker was not ubiquitinated properly by a fish E3 ligase complex. We describe here the generation of a Fucci derivative using zebrafish homologs of Cdt1 and geminin, which provides sweeping views of cell proliferation in whole fish embryos. Remarkably, we discovered two anterior-to-posterior waves of cell-cycle transitions, G1/S and M/G1, in the differentiating notochord. Our study demonstrates the effectiveness of using the Cul4Ddb1-mediated Cdt1 degradation pathway common to all metazoans for the development of a G1 marker that works in the nonmammalian animal model.", "classifications": [ { "id": "Sawano", "label": "Group Sawano", "parent": "Shintaku", "type": "group" }, { "id": "Shintaku", "label": "Team Shintaku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Mayu", "last_name": "Sugiyama", "name": null }, { "creator_type": "author", "first_name": "Asako", "last_name": "Sakaue-Sawano", "name": null }, { "creator_type": "author", "first_name": "Tadahiro", "last_name": "Iimura", "name": null }, { "creator_type": "author", "first_name": "Kiyoko", "last_name": "Fukami", "name": null }, { "creator_type": "author", "first_name": "Tetsuya", "last_name": "Kitaguchi", "name": null }, { "creator_type": "author", "first_name": "Koichi", "last_name": "Kawakami", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Okamoto", "name": null }, { "creator_type": "author", "first_name": "Shin-ichi", "last_name": "Higashijima", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Miyawaki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1073/pnas.0906464106" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "19923430" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Animals, Genetically Modified", "descriptor_ui": "D030801", "major_topic": false }, { "descriptor": "Biomarkers", "descriptor_ui": "D015415", "major_topic": false }, { "descriptor": "Cell Cycle", "descriptor_ui": "D002453", "major_topic": true }, { "descriptor": "Cell Nucleus", "descriptor_ui": "D002467", "major_topic": false }, { "descriptor": "Embryo, Nonmammalian", "descriptor_ui": "D004625", "major_topic": false }, { "descriptor": "Embryonic Development", "descriptor_ui": "D047108", "major_topic": true }, { "descriptor": "Fluorescent Dyes", "descriptor_ui": "D005456", "major_topic": false }, { "descriptor": "G1 Phase", "descriptor_ui": "D016193", "major_topic": false }, { "descriptor": "Mitosis", "descriptor_ui": "D008938", "major_topic": false }, { "descriptor": "Molecular Sequence Data", "descriptor_ui": "D008969", "major_topic": false }, { "descriptor": "Notochord", "descriptor_ui": "D009672", "major_topic": false }, { "descriptor": "Retina", "descriptor_ui": "D012160", "major_topic": false }, { "descriptor": "S Phase", "descriptor_ui": "D016196", "major_topic": false }, { "descriptor": "Time Factors", "descriptor_ui": "D013997", "major_topic": false }, { "descriptor": "Zebrafish", "descriptor_ui": "D015027", "major_topic": false } ], "publication": { "conference_name": null, "date": "2009 Dec 8", "date_precision": "day", "issue": "49", "normalized_date": "2009-12-08", "pages": "20812-20817", "proceedings_title": null, "publisher": "", "title": "Proceedings of the National Academy of Sciences of the United States of America", "volume": "106", "year": 2009 }, "ssbd": { "database": [], "repository": [] }, "title": "Illuminating cell-cycle progression in the developing zebrafish embryo.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "A Pd-catalyzed tetraallylation of C(60) that selectively occurs with an unsymmetrical addition pattern has been established. Treatment of C(60) with CH(2)=CHCH(2)Cl, CH(2)=CHCH(2)SnBu(3), and PdCl(2)[P(OPh)(3)](2) in 1,2-Cl(2)C(6)H(4) at 50 degrees C afforded the tetraallylated fullerene in 74% yield with virtually complete regioselectivity. Mechanistic investigations showed that (i) tetraallylation proceeds through consecutive nucleophilic/electrophilic allylations [likely via a bis(pi-allyl)palladium intermediate] and (ii) both steric (for the first diallylation) and electronic (for the second diallylation) factors are responsible for the high regioselectivity.", "classifications": [ { "id": "Nanbo", "label": "Group Nanbo", "parent": "Tsuchiya", "type": "group" }, { "id": "Tsuchiya", "label": "Team Tsuchiya", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Masakazu", "last_name": "Nambo", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Wakamiya", "name": null }, { "creator_type": "author", "first_name": "Shigehiro", "last_name": "Yamaguchi", "name": null }, { "creator_type": "author", "first_name": "Kenichiro", "last_name": "Itami", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/ja9071173" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "19919157" } }, "mesh": [ { "descriptor": "Allyl Compounds", "descriptor_ui": "D000498", "major_topic": false }, { "descriptor": "Catalysis", "descriptor_ui": "D002384", "major_topic": false }, { "descriptor": "Crystallography, X-Ray", "descriptor_ui": "D018360", "major_topic": false }, { "descriptor": "Fullerenes", "descriptor_ui": "D037741", "major_topic": false }, { "descriptor": "Isomerism", "descriptor_ui": "D007536", "major_topic": false }, { "descriptor": "Molecular Structure", "descriptor_ui": "D015394", "major_topic": false }, { "descriptor": "Palladium", "descriptor_ui": "D010165", "major_topic": false } ], "publication": { "conference_name": null, "date": "2009 Oct 28", "date_precision": "day", "issue": "42", "normalized_date": "2009-10-28", "pages": "15112-15113", "proceedings_title": null, "publisher": "", "title": "Journal of the American Chemical Society", "volume": "131", "year": 2009 }, "ssbd": { "database": [], "repository": [] }, "title": "Regioselective unsymmetrical tetraallylation of C(60) through palladium catalysis.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: A genome-wide association study (GWAS), which assessed multiple ethnicities, reported an association between single nucleotide polymorphisms in the 8q24 region and colorectal cancer risk. Although the association with the identified loci was strong, information on its impact in combination with lifestyle factors is limited. METHODS: We conducted a case-control study in 481 patients with colorectal cancer (CRC) and 962 sex-age matched non-cancer controls. Data on lifestyle factors, including diet, were obtained by self-administered questionnaire. Two 8q24 loci, rs6983267 and rs10090154, were assessed by the TaqMan method. Associations were then assessed by multivariate logistic regression models that considered potential confounders. RESULTS: We found an increased risk of CRC with rs6983267 but not with rs10090154. An allelic OR was 1.22 (1.04-1.44, p for trend = 0.014), which remained significant after adjustment for confounders (OR = 1.25). No statistically significant interaction with potential confounding factors was observed. CONCLUSION: The polymorphism rs6983267 showed a significant association with CRC in a Japanese population. Further investigation of the biological mechanism of this association is warranted.", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Keitaro", "last_name": "Matsuo", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Hidemi", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Satoyo", "last_name": "Hosono", "name": null }, { "creator_type": "author", "first_name": "Takakazu", "last_name": "Kawase", "name": null }, { "creator_type": "author", "first_name": "Miki", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Kohei", "last_name": "Shitara", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Komori", "name": null }, { "creator_type": "author", "first_name": "Yukihide", "last_name": "Kanemitsu", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Hirai", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null }, { "creator_type": "author", "first_name": "Hideo", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Kazuo", "last_name": "Tajima", "name": null } ], "identifiers": { "doi": { "normalized": "10.1186/1471-2407-9-379" }, "pmcid": { "normalized": "PMC2783039" }, "pmid": { "normalized": "19857256" } }, "mesh": [ { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Asian People", "descriptor_ui": "D044466", "major_topic": false }, { "descriptor": "Case-Control Studies", "descriptor_ui": "D016022", "major_topic": false }, { "descriptor": "Chromosomes, Human, Pair 8", "descriptor_ui": "D002898", "major_topic": false }, { "descriptor": "Colorectal Neoplasms", "descriptor_ui": "D015179", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Genetic Predisposition to Disease", "descriptor_ui": "D020022", "major_topic": true }, { "descriptor": "Genome-Wide Association Study", "descriptor_ui": "D055106", "major_topic": false }, { "descriptor": "Genotype", "descriptor_ui": "D005838", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Japan", "descriptor_ui": "D007564", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Polymerase Chain Reaction", "descriptor_ui": "D016133", "major_topic": false }, { "descriptor": "Polymorphism, Single Nucleotide", "descriptor_ui": "D020641", "major_topic": false }, { "descriptor": "Risk Factors", "descriptor_ui": "D012307", "major_topic": false } ], "publication": { "conference_name": null, "date": "2009 Oct 26", "date_precision": "day", "issue": "", "normalized_date": "2009-10-26", "pages": "379", "proceedings_title": null, "publisher": "", "title": "BMC cancer", "volume": "9", "year": 2009 }, "ssbd": { "database": [], "repository": [] }, "title": "Association between an 8q24 locus and the risk of colorectal cancer in Japanese.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Chiral cationic Pd aqua complexes can function as acid-base catalysts, effectively activating active methylene and methine compounds to give chiral Pd enolates. It is noteworthy that such enolate formation occurs with concomitant formation of a strong protic acid. Although the reactivity of the Pd enolate itself is not sufficient for reactions with carbon-based electrophiles, its cooperative action with the protic acid to activate the electrophiles allows the desired C-C bond-forming reactions to proceed smoothly in a highly enantioselective manner. Based on this mechanistic feature, reactions with acetals have been developed; these are difficult to achieve using conventional basic enolate chemistry.", "classifications": [ { "id": "Sodeoka", "label": "Group Sodeoka", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Mikiko", "last_name": "Sodeoka", "name": null }, { "creator_type": "author", "first_name": "Yoshitaka", "last_name": "Hamashima", "name": null } ], "identifiers": { "doi": { "normalized": "10.1039/b911015a" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "19787104" } }, "mesh": [], "publication": { "conference_name": null, "date": "2009 Oct 21", "date_precision": "day", "issue": "39", "normalized_date": "2009-10-21", "pages": "5787-5798", "proceedings_title": null, "publisher": "", "title": "Chemical communications (Cambridge, England)", "volume": "", "year": 2009 }, "ssbd": { "database": [], "repository": [] }, "title": "Chiral Pd aqua complex-catalyzed asymmetric C-C bond-forming reactions: a Bronsted acid-base cooperative system.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Coordinated recovery of hepatic glucose metabolism is prerequisite for normal liver regeneration. To examine roles of hypoxia inducible factor-1alpha (HIF-1alpha) for hepatic glucose homeostasis during the reparative process, we inactivated the gene in hepatocytes in vivo. Following partial hepatectomy (PH), recovery of residual liver weight was initially retarded in the mutant mice by down-regulation of hepatocyte proliferation, but occurred comparably between the mutant and control mice at 72h after PH. At this time point, the mutant mice showed lowered blood glucose levels with enhanced accumulation of glycogen in the liver. The mutant mice exhibited impairment of hepatic gluconeogenesis as assessed by alanine tolerance test. This appeared to result from reduced expression of PGK-1 and PEPCK since 3-PG, PEP and malate were accumulated to greater extents in the regenerated liver. In conclusion, these findings provide evidence for roles of HIF-1alpha in the regulation of gluconeogenesis under liver regeneration.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Toshihide", "last_name": "Tajima", "name": null }, { "creator_type": "author", "first_name": "Nobuhito", "last_name": "Goda", "name": null }, { "creator_type": "author", "first_name": "Natsuko", "last_name": "Fujiki", "name": null }, { "creator_type": "author", "first_name": "Takako", "last_name": "Hishiki", "name": null }, { "creator_type": "author", "first_name": "Yasumasa", "last_name": "Nishiyama", "name": null }, { "creator_type": "author", "first_name": "Nanami", "last_name": "Senoo-Matsuda", "name": null }, { "creator_type": "author", "first_name": "Motohide", "last_name": "Shimazu", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Yasunori", "last_name": "Yoshimura", "name": null }, { "creator_type": "author", "first_name": "Randall S.", "last_name": "Johnson", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Suematsu", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.bbrc.2009.07.115" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "19643083" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Blood Glucose", "descriptor_ui": "D001786", "major_topic": false }, { "descriptor": "DNA Replication", "descriptor_ui": "D004261", "major_topic": false }, { "descriptor": "Gluconeogenesis", "descriptor_ui": "D005943", "major_topic": false }, { "descriptor": "Glycogen", "descriptor_ui": "D006003", "major_topic": false }, { "descriptor": "Hepatocytes", "descriptor_ui": "D022781", "major_topic": false }, { "descriptor": "Hypoxia-Inducible Factor 1, alpha Subunit", "descriptor_ui": "D051795", "major_topic": false }, { "descriptor": "Liver Regeneration", "descriptor_ui": "D008115", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Mutant Strains", "descriptor_ui": "D008817", "major_topic": false } ], "publication": { "conference_name": null, "date": "2009 Oct 2", "date_precision": "day", "issue": "4", "normalized_date": "2009-10-02", "pages": "789-794", "proceedings_title": null, "publisher": "", "title": "Biochemical and biophysical research communications", "volume": "387", "year": 2009 }, "ssbd": { "database": [], "repository": [] }, "title": "HIF-1alpha is necessary to support gluconeogenesis during liver regeneration.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "We examined the diagnostic accuracy of the cumulative smoking dose for identifying the epidermal growth factor receptor (EGFR) exon 19 deletion and L858R mutation among Japanese patients with non-small-cell lung cancer (NSCLC). EGFR mutations in exon 19 and exon 21 were determined in 1001 NSCLC patients. A receiver-operating characteristic (ROC) curve methodology was applied to estimate the diagnostic accuracy. EGFR mutations were detected in 314 patients (31.4%). A cumulative smoking dose of less than 13 pack-years (PY) was the optimal cut-off point for predicting a positive EGFR mutation status, producing a balance between the sensitivity (73.5%) and the specificity (77%). The area under the ROC curve was 0.77, indicating that the smoking dose had a moderate diagnostic accuracy. The median survival time or the median progression-free survival time of patients who had smoked less than 13 pack-years (PY) were 18.6 and 6.3 months, respectively, while those of patients with equal to or more than 13 PY were 9.6 and 2.4 months, respectively. The overall survival (OS) and progression-free survival (PFS) rates were significantly different between the two groups (OS: hazard ratio [HR] = 0.64, 95% confidence interval [CI] = 0.51-0.80, P = 0.0001) (PFS: HR = 0.58, 95% CI = 0.47-0.71, P < 0.0001). Our study indicated that the smoking dose predicted EGFR mutations with a moderate diagnostic accuracy. Thus, patients who have smoked less than 13 PY might be candidates for gefitinib treatment when EGFR mutation status cannot be determined.", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Masaru", "last_name": "Jida", "name": null }, { "creator_type": "author", "first_name": "Shinichi", "last_name": "Toyooka", "name": null }, { "creator_type": "author", "first_name": "Tetsuya", "last_name": "Mitsudomi", "name": null }, { "creator_type": "author", "first_name": "Toshimi", "last_name": "Takano", "name": null }, { "creator_type": "author", "first_name": "Keitaro", "last_name": "Matsuo", "name": null }, { "creator_type": "author", "first_name": "Katsuyuki", "last_name": "Hotta", "name": null }, { "creator_type": "author", "first_name": "Kazunori", "last_name": "Tsukuda", "name": null }, { "creator_type": "author", "first_name": "Takafumi", "last_name": "Kubo", "name": null }, { "creator_type": "author", "first_name": "Hiromasa", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Masaomi", "last_name": "Yamane", "name": null }, { "creator_type": "author", "first_name": "Takahiro", "last_name": "Oto", "name": null }, { "creator_type": "author", "first_name": "Yoshifumi", "last_name": "Sano", "name": null }, { "creator_type": "author", "first_name": "Katsuyuki", "last_name": "Kiura", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null }, { "creator_type": "author", "first_name": "Yuichiro", "last_name": "Ohe", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Date", "name": null }, { "creator_type": "author", "first_name": "Shinichiro", "last_name": "Miyoshi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/j.1349-7006.2009.01273.x" }, "pmcid": { "normalized": "PMC11158181" }, "pmid": { "normalized": "19650855" } }, "mesh": [ { "descriptor": "Antineoplastic Agents", "descriptor_ui": "D000970", "major_topic": false }, { "descriptor": "Area Under Curve", "descriptor_ui": "D019540", "major_topic": false }, { "descriptor": "Carcinoma, Non-Small-Cell Lung", "descriptor_ui": "D002289", "major_topic": false }, { "descriptor": "Disease-Free Survival", "descriptor_ui": "D018572", "major_topic": false }, { "descriptor": "DNA Mutational Analysis", "descriptor_ui": "D004252", "major_topic": false }, { "descriptor": "Drug Resistance, Neoplasm", "descriptor_ui": "D019008", "major_topic": false }, { "descriptor": "ErbB Receptors", "descriptor_ui": "D066246", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Gefitinib", "descriptor_ui": "D000077156", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Kaplan-Meier Estimate", "descriptor_ui": "D053208", "major_topic": false }, { "descriptor": "Lung Neoplasms", "descriptor_ui": "D008175", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": false }, { "descriptor": "Quinazolines", "descriptor_ui": "D011799", "major_topic": false }, { "descriptor": "ROC Curve", "descriptor_ui": "D012372", "major_topic": false }, { "descriptor": "Sensitivity and Specificity", "descriptor_ui": "D012680", "major_topic": false }, { "descriptor": "Smoking", "descriptor_ui": "D012907", "major_topic": false } ], "publication": { "conference_name": null, "date": "2009-10", "date_precision": "month", "issue": "10", "normalized_date": "2009-10", "pages": "1931-1934", "proceedings_title": null, "publisher": "", "title": "Cancer Science", "volume": "100", "year": 2009 }, "ssbd": { "database": [], "repository": [] }, "title": "Usefulness of cumulative smoking dose for identifying the EGFR mutation and patients with non-small-cell lung cancer for gefitinib treatment", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "One of the adaptive behaviors of animals in their environment is thermotaxis, by which they migrate toward a preferred temperature. This sensorimotor integration is accomplished by choosing one of two behaviors depending on the surrounding temperature, namely thermophilic or cryophilic movement. Caenorhabditis elegans exhibits thermotaxis and its migration behavior has been analyzed experimentally at both the population and individual levels. However, some experimental data are inconsistent especially for thermophilic movement, which is expected to be observed in lower than favorable temperatures. There are no experimental analyzes that find thermophilic tendencies in the individual behavior of worms, despite multiple reports supporting thermophilic movement of the population. Although theoretical methods have been used to study thermotaxis of C. elegans, no mathematical model provides a consistent explanation for this discrepancy. Here we develop a simple biased random walk model, which describes population behavior, but which is based on the results of individual assays. Our model can integrate all previous experiments without any contradiction. We regenerate all the population patterns reported in past studies and give a consistent explanation for the conflicting results. Our results suggest that thermophilic movement is observed, even in individual movements, when the thermal gradient is sufficiently slight. On the contrary, thermophilic movement disappears when the thermal gradient is too steep. The thermal gradient is thus essential for a comprehensive understanding of the experimental studies of thermotaxis in C. elegans. Our model provides insight into an integrative understanding of the neural activity and thermotactic behavior in C. elegans.", "classifications": [ { "id": "Mochizuki", "label": "Group Mochizuki", "parent": "Eiraku", "type": "group" }, { "id": "Eiraku", "label": "Team Eiraku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Kenichi", "last_name": "Nakazato", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Mochizuki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.jtbi.2009.05.027" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "19501104" } }, "mesh": [ { "descriptor": "Adaptation, Physiological", "descriptor_ui": "D000222", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Behavior, Animal", "descriptor_ui": "D001522", "major_topic": false }, { "descriptor": "Caenorhabditis elegans", "descriptor_ui": "D017173", "major_topic": false }, { "descriptor": "Hot Temperature", "descriptor_ui": "D006358", "major_topic": true }, { "descriptor": "Locomotion", "descriptor_ui": "D008124", "major_topic": false }, { "descriptor": "Models, Biological", "descriptor_ui": "D008954", "major_topic": true }, { "descriptor": "Thermosensing", "descriptor_ui": "D013697", "major_topic": false } ], "publication": { "conference_name": null, "date": "2009 Sep 7", "date_precision": "day", "issue": "1", "normalized_date": "2009-09-07", "pages": "56-65", "proceedings_title": null, "publisher": "", "title": "Journal of theoretical biology", "volume": "260", "year": 2009 }, "ssbd": { "database": [], "repository": [] }, "title": "Steepness of thermal gradient is essential to obtain a unified view of thermotaxis in C. elegans.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "mdm2 and mdmx oncogenes play essential yet non-redundant roles in synergistic inactivation of the tumor suppressor, p53. While Mdm2 inhibits p53 activity mainly by augmenting its ubiquitination, the functional role of Mdmx on p53 ubiquitination remains obscure. In transfected H1299 cells, Mdmx augmented Mdm2-mediated ubiquitination of p53. In in vitro ubiquitination assays, the Mdmx/Mdm2 heteromeric complex, in comparison to the Mdm2 homomer, showed enhanced ubiquitinase activity toward p53 and the reduced auto-ubiquitination of Mdm2. Alteration of the substrate specificity via binding to Mdmx may contribute to efficient ubiquitination and inactivation of p53 by Mdm2.", "classifications": [ { "id": "Okamoto", "label": "Group Okamoto", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Koji", "last_name": "Okamoto", "name": null }, { "creator_type": "author", "first_name": "Yoichi", "last_name": "Taya", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Nakagama", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.febslet.2009.07.021" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "19619542" } }, "mesh": [ { "descriptor": "Cell Cycle Proteins", "descriptor_ui": "D018797", "major_topic": false }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Nuclear Proteins", "descriptor_ui": "D009687", "major_topic": false }, { "descriptor": "Proto-Oncogene Proteins", "descriptor_ui": "D011518", "major_topic": false }, { "descriptor": "Proto-Oncogene Proteins c-mdm2", "descriptor_ui": "D051736", "major_topic": false }, { "descriptor": "Substrate Specificity", "descriptor_ui": "D013379", "major_topic": false }, { "descriptor": "Tumor Suppressor Protein p53", "descriptor_ui": "D016159", "major_topic": false }, { "descriptor": "Ubiquitination", "descriptor_ui": "D054875", "major_topic": false } ], "publication": { "conference_name": null, "date": "2009 Sep 3", "date_precision": "day", "issue": "17", "normalized_date": "2009-09-03", "pages": "2710-2714", "proceedings_title": null, "publisher": "", "title": "FEBS letters", "volume": "583", "year": 2009 }, "ssbd": { "database": [], "repository": [] }, "title": "Mdmx enhances p53 ubiquitination by altering the substrate preference of the Mdm2 ubiquitin ligase.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Stem cells do not all respond the same way, but the mechanisms underlying this heterogeneity are not well understood. Here, we found that expression of Hes1 and its downstream genes oscillate in mouse embryonic stem (ES) cells. Those expressing low and high levels of Hes1 tended to differentiate into neural and mesodermal cells, respectively. Furthermore, inactivation of Hes1 facilitated neural differentiation more uniformly at earlier time. Thus, Hes1-null ES cells display less heterogeneity in both the differentiation timing and fate choice, suggesting that the cyclic gene Hes1 contributes to heterogeneous responses of ES cells even under the same environmental conditions.", "classifications": [ { "id": "Imayoshi", "label": "Group Imayoshi", "parent": "Imayoshi", "type": "group" }, { "id": "Imayoshi", "label": "Team Imayoshi", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Taeko", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Hiroaki", "last_name": "Mizuno", "name": null }, { "creator_type": "author", "first_name": "Itaru", "last_name": "Imayoshi", "name": null }, { "creator_type": "author", "first_name": "Chikara", "last_name": "Furusawa", "name": null }, { "creator_type": "author", "first_name": "Katsuhiko", "last_name": "Shirahige", "name": null }, { "creator_type": "author", "first_name": "Ryoichiro", "last_name": "Kageyama", "name": null } ], "identifiers": { "doi": { "normalized": "10.1101/gad.1823109" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "19684110" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Basic Helix-Loop-Helix Proteins", "descriptor_ui": "D051792", "major_topic": false }, { "descriptor": "Cell Cycle Proteins", "descriptor_ui": "D018797", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": true }, { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "Embryonic Stem Cells", "descriptor_ui": "D053595", "major_topic": false }, { "descriptor": "Gene Expression Regulation, Developmental", "descriptor_ui": "D018507", "major_topic": true }, { "descriptor": "Gene Silencing", "descriptor_ui": "D020868", "major_topic": false }, { "descriptor": "Homeodomain Proteins", "descriptor_ui": "D018398", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Receptors, Notch", "descriptor_ui": "D051880", "major_topic": false }, { "descriptor": "Transcription Factor HES-1", "descriptor_ui": "D000072056", "major_topic": false } ], "publication": { "conference_name": null, "date": "2009 Aug 15", "date_precision": "day", "issue": "16", "normalized_date": "2009-08-15", "pages": "1870-1875", "proceedings_title": null, "publisher": "", "title": "Genes & Development", "volume": "23", "year": 2009 }, "ssbd": { "database": [], "repository": [] }, "title": "The cyclic gene Hes1 contributes to diverse differentiation responses of embryonic stem cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: Influenza virus infection causes significant morbidity and mortality and has marked social and economic impacts throughout the world. The influenza surface glycoproteins, hemagglutinin (HA) and neuraminidase (NA), act cooperatively to support efficient influenza A virus replication and provide the most important targets for anti-influenza chemotherapy. In this study, povidone-iodine (PVP-I), which has a broad-spectrum microbicidal property, was examined for its inhibitory effects against influenza virus infection in MDCK cells and the mechanisms of PVP-I action on HA and NA were revealed. RESULTS: Results obtained using a novel fluorescence- and chromogenic-based plaque inhibition assay showed that 1.56 mg/ml PVP-I inhibited infections in MDCK cells of human (8 strains) and avian (5 strains) influenza A viruses, including H1N1, H3N2, H5N3 and H9N2, from 23.0-97.5%. A sialidase inhibition assay revealed that PVP-I inhibited N1, N2 and N3 neuraminidases with IC50 values of 9.5-212.1 microg/ml by a mixed-type inhibition mechanism. Receptor binding inhibition and hemagglutinin inhibition assays indicated that PVP-I affected viral hemagglutinin rather than host-specific sialic acid receptors. CONCLUSION: Mechanisms of reduction of viral growth in MDCK cells by PVP-I involve blockade of viral attachment to cellular receptors and inhibition of viral release and spread from infected cells. Therefore, PVP-I is useful to prevent infection and limit spread of human and avian influenza viruses.", "classifications": [ { "id": "Suzuki", "label": "Group Suzuki", "parent": "Takekawa", "type": "group" }, { "id": "Takekawa", "label": "Team Takekawa", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Nongluk", "last_name": "Sriwilaijaroen", "name": null }, { "creator_type": "author", "first_name": "Prapon", "last_name": "Wilairat", "name": null }, { "creator_type": "author", "first_name": "Hiroaki", "last_name": "Hiramatsu", "name": null }, { "creator_type": "author", "first_name": "Tadanobu", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Morihiro", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Yasuhiko", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Masato", "last_name": "Tashiro", "name": null }, { "creator_type": "author", "first_name": "Yasuo", "last_name": "Suzuki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1186/1743-422x-6-124" }, "pmcid": { "normalized": "PMC2739848" }, "pmid": { "normalized": "19678928" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Antiviral Agents", "descriptor_ui": "D000998", "major_topic": false }, { "descriptor": "Birds", "descriptor_ui": "D001717", "major_topic": false }, { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "Chick Embryo", "descriptor_ui": "D002642", "major_topic": false }, { "descriptor": "Guinea Pigs", "descriptor_ui": "D006168", "major_topic": false }, { "descriptor": "Hemagglutination", "descriptor_ui": "D006384", "major_topic": false }, { "descriptor": "Hemagglutinin Glycoproteins, Influenza Virus", "descriptor_ui": "D019267", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Influenza A virus", "descriptor_ui": "D009980", "major_topic": false }, { "descriptor": "Influenza A Virus, H1N1 Subtype", "descriptor_ui": "D053118", "major_topic": false }, { "descriptor": "Influenza A Virus, H3N2 Subtype", "descriptor_ui": "D053122", "major_topic": false }, { "descriptor": "Influenza A Virus, H5N1 Subtype", "descriptor_ui": "D053124", "major_topic": false }, { "descriptor": "Influenza A Virus, H9N2 Subtype", "descriptor_ui": "D053127", "major_topic": false }, { "descriptor": "Influenza in Birds", "descriptor_ui": "D005585", "major_topic": false }, { "descriptor": "Influenza, Human", "descriptor_ui": "D007251", "major_topic": false }, { "descriptor": "Neuraminidase", "descriptor_ui": "D009439", "major_topic": false }, { "descriptor": "Povidone-Iodine", "descriptor_ui": "D011206", "major_topic": false } ], "publication": { "conference_name": null, "date": "2009 Aug 13", "date_precision": "day", "issue": "", "normalized_date": "2009-08-13", "pages": "124", "proceedings_title": null, "publisher": "", "title": "Virology journal", "volume": "6", "year": 2009 }, "ssbd": { "database": [], "repository": [] }, "title": "Mechanisms of the action of povidone-iodine against human and avian influenza A viruses: its effects on hemagglutination and sialidase activities.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "We propose two-photon excited fluorescence (TPEF) microscopy employing a novel phase modulation technique of ultra-broadband laser pulses, which allows the relative excitation of an individual fluorophore with respect to other fluorophores. This technique is based on the generation of multi-wavelength pulse train, which independently interacts with each fluorophore. Our technique is applied to dual-color imaging of cells expressing two types of fluorescent proteins. We achieve the selective excitation of one over the other and vice versa. The product of the maximum contrast ratios exceeds 100. We also demonstrate yielded equal excitation rates in the simultaneous excitation. By the selective excitation of a donor fluorescent protein, fluorescence resonance energy transfer imaging is also achieved.", "classifications": [ { "id": "Isobe", "label": "Group Isobe", "parent": "Imayoshi", "type": "group" }, { "id": "Imayoshi", "label": "Team Imayoshi", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Keisuke", "last_name": "Isobe", "name": null }, { "creator_type": "author", "first_name": "Akira", "last_name": "Suda", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Fumihiko", "last_name": "Kannari", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Kawano", "name": null }, { "creator_type": "author", "first_name": "Hideaki", "last_name": "Mizuno", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Miyawaki", "name": null }, { "creator_type": "author", "first_name": "Katsumi", "last_name": "Midorikawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1364/oe.17.013737" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "19654781" } }, "mesh": [ { "descriptor": "Computer Simulation", "descriptor_ui": "D003198", "major_topic": false }, { "descriptor": "Computer-Aided Design", "descriptor_ui": "D017076", "major_topic": false }, { "descriptor": "Equipment Design", "descriptor_ui": "D004867", "major_topic": false }, { "descriptor": "Equipment Failure Analysis", "descriptor_ui": "D019544", "major_topic": false }, { "descriptor": "Lasers", "descriptor_ui": "D007834", "major_topic": true }, { "descriptor": "Light", "descriptor_ui": "D008027", "major_topic": false }, { "descriptor": "Lighting", "descriptor_ui": "D008029", "major_topic": false }, { "descriptor": "Microscopy, Fluorescence, Multiphoton", "descriptor_ui": "D036641", "major_topic": false }, { "descriptor": "Models, Theoretical", "descriptor_ui": "D008962", "major_topic": false }, { "descriptor": "Optical Devices", "descriptor_ui": "D055096", "major_topic": true }, { "descriptor": "Scattering, Radiation", "descriptor_ui": "D012542", "major_topic": false } ], "publication": { "conference_name": null, "date": "2009 Aug 3", "date_precision": "day", "issue": "16", "normalized_date": "2009-08-03", "pages": "13737-13746", "proceedings_title": null, "publisher": "", "title": "Optics express", "volume": "17", "year": 2009 }, "ssbd": { "database": [], "repository": [] }, "title": "Multifarious control of two-photon excitation of multiple fluorophores achieved by phase modulation of ultra-broadband laser pulses.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "We describe a sheath flow capillary electrophoresis time-of-flight mass spectrometry (CE-TOFMS) method in the negative mode using a platinum electrospray ionization (ESI) spray needle, which allows the comprehensive analysis of anionic metabolites. The material of the spray needle had significant effect on the measurement of anions. A stainless steel spray needle was oxidized and corroded at the anodic electrode due to electrolysis. The precipitation of iron oxides (rust) plugged the capillary outlet, resulting in shortened capillary lifetime. Many anionic metabolites also formed complexes with the iron oxides or migrating nickel ion, which was also generated by electrolysis and moved toward the cathode (the capillary inlet). The metal-anion complex formation significantly reduced detection sensitivity of the anionic compounds. The use of a platinum ESI needle prevented both oxidation of the metals and needle corrosion. Sensitivity using the platinum needle increased from several- to 63-fold, with the largest improvements for anions exhibiting high metal chelating properties such as carboxylic acids, nucleotides, and coenzyme A compounds. The detection limits for most anions were between 0.03 and 0.87 micromol/L (0.8 and 24 fmol) at a signal-to-noise ratio of 3. This method is quantitative, sensitive, and robust, and its utility was demonstrated by the analysis of the metabolites in the central metabolic pathways extracted from mouse liver.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Kaori", "last_name": "Igarashi", "name": null }, { "creator_type": "author", "first_name": "Chiharu", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Katsuo", "last_name": "Mizobuchi", "name": null }, { "creator_type": "author", "first_name": "Hans-Peter", "last_name": "Zimmermann", "name": null }, { "creator_type": "author", "first_name": "Masaru", "last_name": "Tomita", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/ac900675k" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "19522513" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Anions", "descriptor_ui": "D000838", "major_topic": false }, { "descriptor": "Biomarkers", "descriptor_ui": "D015415", "major_topic": false }, { "descriptor": "Electrophoresis, Capillary", "descriptor_ui": "D019075", "major_topic": false }, { "descriptor": "Hepatocytes", "descriptor_ui": "D022781", "major_topic": false }, { "descriptor": "Mass Spectrometry", "descriptor_ui": "D013058", "major_topic": true }, { "descriptor": "Metabolomics", "descriptor_ui": "D055432", "major_topic": true }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Platinum", "descriptor_ui": "D010984", "major_topic": false }, { "descriptor": "Sensitivity and Specificity", "descriptor_ui": "D012680", "major_topic": false }, { "descriptor": "Stainless Steel", "descriptor_ui": "D013193", "major_topic": false } ], "publication": { "conference_name": null, "date": "2009 Aug 1", "date_precision": "day", "issue": "15", "normalized_date": "2009-08-01", "pages": "6165-6174", "proceedings_title": null, "publisher": "", "title": "Analytical chemistry", "volume": "81", "year": 2009 }, "ssbd": { "database": [], "repository": [] }, "title": "Metabolomic profiling of anionic metabolites by capillary electrophoresis mass spectrometry.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "We demonstrate two complementary types of microscopy using an identical setup for single-pulse coherent anti-Stokes Raman scattering (CARS) imaging, which employs an ultrabroadband laser pulse with a spectral bandwidth of 4800 cm(-1) and enables the suppression of nonresonant CARS signals. One is a novel type of microscopy that uses spectral phase modulation for the selective excitation of a single Raman mode. The selective excitation is achieved by the modulated pulse focusing its difference-frequency spectrum into a narrow spectral region. Another type is Fourier-transform CARS (FT-CARS) microspectroscopy based on the measurement of the CARS spectrum obtained from the Fourier-transform of the interferometric autocorrelation (IAC) signal. Vibrational spectral imaging of chemical and biological samples is demonstrated using the two types of microscopy.", "classifications": [ { "id": "Isobe", "label": "Group Isobe", "parent": "Imayoshi", "type": "group" }, { "id": "Imayoshi", "label": "Team Imayoshi", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Keisuke", "last_name": "Isobe", "name": null }, { "creator_type": "author", "first_name": "Akira", "last_name": "Suda", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Fumihiko", "last_name": "Kannari", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Kawano", "name": null }, { "creator_type": "author", "first_name": "Hideaki", "last_name": "Mizuno", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Miyawaki", "name": null }, { "creator_type": "author", "first_name": "Katsumi", "last_name": "Midorikawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1364/oe.17.011259" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "19582038" } }, "mesh": [ { "descriptor": "Algorithms", "descriptor_ui": "D000465", "major_topic": false }, { "descriptor": "Equipment Design", "descriptor_ui": "D004867", "major_topic": false }, { "descriptor": "Fourier Analysis", "descriptor_ui": "D005583", "major_topic": false }, { "descriptor": "HeLa Cells", "descriptor_ui": "D006367", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Interferometry", "descriptor_ui": "D007368", "major_topic": false }, { "descriptor": "Lasers", "descriptor_ui": "D007834", "major_topic": false }, { "descriptor": "Mitochondria", "descriptor_ui": "D008928", "major_topic": false }, { "descriptor": "Optics and Photonics", "descriptor_ui": "D055095", "major_topic": false }, { "descriptor": "Spectrum Analysis, Raman", "descriptor_ui": "D013059", "major_topic": false }, { "descriptor": "Time Factors", "descriptor_ui": "D013997", "major_topic": false } ], "publication": { "conference_name": null, "date": "2009 Jul 6", "date_precision": "day", "issue": "14", "normalized_date": "2009-07-06", "pages": "11259-11266", "proceedings_title": null, "publisher": "", "title": "Optics express", "volume": "17", "year": 2009 }, "ssbd": { "database": [], "repository": [] }, "title": "Single-pulse coherent anti-Stokes Raman scattering microscopy employing an octave spanning pulse.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "This study was performed to understand the anatomical substrates of amygdaloid modulation of feeding-related peptides-containing neurons in the lateral hypothalamic area (LHA). After biotinylated dextranamine (BDA) injection into the central amygdaloid nucleus (CeA) and immunostaining of melanin-concentrating hormone (MCH)- or orexin (ORX)-containing hypothalamic neurons in the mouse, the prominent overlap of the distribution field of the BDA-labeled fibers and that of the MCH-immunoreactive (ir) or ORX-ir neurons was found in the dorsolateral part of the LHA, and the labeled axon terminals made symmetrical synaptic contacts with somata and dendrites of the MCH-ir or ORX-ir neurons. It was further revealed that nearly all the BDA-labeled axon terminals in the dorsolateral part of LHA were immunoreactive for glutamic acid decarboxylase, an enzyme for conversion of glutamic acid to gamma-aminobutyric acid (GABA). The present data suggest that the CeA is involved in the regulation of feeding behavior by exerting its GABAergic inhibitory action upon the MCH- and ORX-containing LHA neurons.", "classifications": [ { "id": "Yokota", "label": "Group Yokota", "parent": "Enomoto", "type": "group" }, { "id": "Enomoto", "label": "Team Enomoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Sawako", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Toshiko", "last_name": "Tsumori", "name": null }, { "creator_type": "author", "first_name": "Shigefumi", "last_name": "Yokota", "name": null }, { "creator_type": "author", "first_name": "Tatsuro", "last_name": "Oka", "name": null }, { "creator_type": "author", "first_name": "Yukihiko", "last_name": "Yasui", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.brainres.2009.04.049" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "19414001" } }, "mesh": [ { "descriptor": "Amygdala", "descriptor_ui": "D000679", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Axons", "descriptor_ui": "D001369", "major_topic": false }, { "descriptor": "Feeding Behavior", "descriptor_ui": "D005247", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Hypothalamic Hormones", "descriptor_ui": "D007028", "major_topic": false }, { "descriptor": "Hypothalamus", "descriptor_ui": "D007031", "major_topic": false }, { "descriptor": "Immunohistochemistry", "descriptor_ui": "D007150", "major_topic": false }, { "descriptor": "Intracellular Signaling Peptides and Proteins", "descriptor_ui": "D047908", "major_topic": false }, { "descriptor": "Melanins", "descriptor_ui": "D008543", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Microscopy, Electron, Transmission", "descriptor_ui": "D046529", "major_topic": false }, { "descriptor": "Neural Pathways", "descriptor_ui": "D009434", "major_topic": false }, { "descriptor": "Neuropeptides", "descriptor_ui": "D009479", "major_topic": false }, { "descriptor": "Orexins", "descriptor_ui": "D000068797", "major_topic": false }, { "descriptor": "Pituitary Hormones", "descriptor_ui": "D010907", "major_topic": false } ], "publication": { "conference_name": null, "date": "2009 Jun 30", "date_precision": "day", "issue": "", "normalized_date": "2009-06-30", "pages": "66-74", "proceedings_title": null, "publisher": "", "title": "Brain research", "volume": "1278", "year": 2009 }, "ssbd": { "database": [], "repository": [] }, "title": "Amygdaloid axons innervate melanin-concentrating hormone- and orexin-containing neurons in the mouse lateral hypothalamus.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Detection of internal body time (BT) via a few-time-point assay has been a longstanding challenge in medicine, because BT information can be exploited to maximize potency and minimize toxicity during drug administration and thus will enable highly optimized medication. To address this challenge, we previously developed the concept, \"molecular-timetable method,\" which was originally inspired by Linne's flower clock. In Linne's flower clock, one can estimate the time of the day by watching the opening and closing pattern of various flowers. Similarly, in the molecular-timetable method, one can measure the BT of the day by profiling the up and down patterns of substances in the molecular timetable. To make this method clinically feasible, we now performed blood metabolome analysis and here report the successful quantification of hundreds of clock-controlled metabolites in mouse plasma. Based on circadian blood metabolomics, we can detect individual BT under various conditions, demonstrating its robustness against genetic background, sex, age, and feeding differences. The power of this method is also demonstrated by the sensitive and accurate detection of circadian rhythm disorder in jet-lagged mice. These results suggest the potential for metabolomics-based detection of BT (\"metabolite-timetable method\"), which will lead to the realization of chronotherapy and personalized medicine.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yoichi", "last_name": "Minami", "name": null }, { "creator_type": "author", "first_name": "Takeya", "last_name": "Kasukawa", "name": null }, { "creator_type": "author", "first_name": "Yuji", "last_name": "Kakazu", "name": null }, { "creator_type": "author", "first_name": "Masayuki", "last_name": "Iigo", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Sugimoto", "name": null }, { "creator_type": "author", "first_name": "Satsuki", "last_name": "Ikeda", "name": null }, { "creator_type": "author", "first_name": "Akira", "last_name": "Yasui", "name": null }, { "creator_type": "author", "first_name": "Gijsbertus T. J.", "last_name": "van der Horst", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Hiroki R.", "last_name": "Ueda", "name": null } ], "identifiers": { "doi": { "normalized": "10.1073/pnas.0900617106" }, "pmcid": { "normalized": "PMC2689311" }, "pmid": { "normalized": "19487679" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Biological Clocks", "descriptor_ui": "D001683", "major_topic": true }, { "descriptor": "Blood", "descriptor_ui": "D001769", "major_topic": false }, { "descriptor": "Chromatography, Liquid", "descriptor_ui": "D002853", "major_topic": false }, { "descriptor": "Circadian Rhythm", "descriptor_ui": "D002940", "major_topic": true }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Jet Lag Syndrome", "descriptor_ui": "D020179", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mass Spectrometry", "descriptor_ui": "D013058", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred CBA", "descriptor_ui": "D008808", "major_topic": false } ], "publication": { "conference_name": null, "date": "2009 Jun 16", "date_precision": "day", "issue": "24", "normalized_date": "2009-06-16", "pages": "9890-9895", "proceedings_title": null, "publisher": "", "title": "Proceedings of the National Academy of Sciences of the United States of America", "volume": "106", "year": 2009 }, "ssbd": { "database": [], "repository": [] }, "title": "Measurement of internal body time by blood metabolomics.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The search for novel enzymes and enzymatic activities is important to map out all metabolic activities and reveal cellular metabolic processes in a more exhaustive manner. Here we present biochemical and physiological evidence for the function of the uncharacterized protein YihU in Escherichia coli using metabolite profiling by capillary electrophoresis time-of-flight mass spectrometry. To detect enzymatic activity and simultaneously identify possible substrates and products of the putative enzyme, we profiled a complex mixture of metabolites in the presence or absence of YihU. In this manner, succinic semialdehyde was identified as a substrate for YihU. The purified YihU protein catalyzed in vitro the NADH-dependent reduction of succinic semialdehyde to gamma-hydroxybutyrate. Moreover, a yihU deletion mutant displayed reduced tolerance to the cytotoxic effects of exogenous addition of succinic semialdehyde. Profiling of intracellular metabolites following treatment of E. coli with succinic semialdehyde supports the existence of a YihU-catalyzed reduction of succinic semialdehyde to gamma-hydroxybutyrate in addition to its known oxidation to succinate and through the tricarboxylic acid cycle. These findings suggest that YihU is a novel gamma-hydroxybutyrate dehydrogenase involved in the metabolism of succinic semialdehyde, and other potentially toxic intermediates that may accumulate under stress conditions in E. coli.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Natsumi", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Martin", "last_name": "Robert", "name": null }, { "creator_type": "author", "first_name": "Hayataro", "last_name": "Kochi", "name": null }, { "creator_type": "author", "first_name": "Goh", "last_name": "Matsuo", "name": null }, { "creator_type": "author", "first_name": "Yuji", "last_name": "Kakazu", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Masaru", "last_name": "Tomita", "name": null } ], "identifiers": { "doi": { "normalized": "10.1074/jbc.m109.002089" }, "pmcid": { "normalized": "PMC2713508" }, "pmid": { "normalized": "19372223" } }, "mesh": [ { "descriptor": "Alcohol Oxidoreductases", "descriptor_ui": "D000429", "major_topic": false }, { "descriptor": "Amino Acid Sequence", "descriptor_ui": "D000595", "major_topic": false }, { "descriptor": "Arabidopsis", "descriptor_ui": "D017360", "major_topic": false }, { "descriptor": "Enzyme Activation", "descriptor_ui": "D004789", "major_topic": false }, { "descriptor": "Escherichia coli K12", "descriptor_ui": "D048168", "major_topic": false }, { "descriptor": "Escherichia coli Proteins", "descriptor_ui": "D029968", "major_topic": false }, { "descriptor": "gamma-Aminobutyric Acid", "descriptor_ui": "D005680", "major_topic": false }, { "descriptor": "Hydroxybutyrate Dehydrogenase", "descriptor_ui": "D006884", "major_topic": false }, { "descriptor": "Metabolome", "descriptor_ui": "D055442", "major_topic": true }, { "descriptor": "Molecular Sequence Data", "descriptor_ui": "D008969", "major_topic": false }, { "descriptor": "Sequence Homology, Amino Acid", "descriptor_ui": "D017386", "major_topic": false }, { "descriptor": "Sodium Oxybate", "descriptor_ui": "D012978", "major_topic": false }, { "descriptor": "Stress, Physiological", "descriptor_ui": "D013312", "major_topic": false }, { "descriptor": "Succinate-Semialdehyde Dehydrogenase", "descriptor_ui": "D050644", "major_topic": false } ], "publication": { "conference_name": null, "date": "2009 Jun 12", "date_precision": "day", "issue": "24", "normalized_date": "2009-06-12", "pages": "16442-16451", "proceedings_title": null, "publisher": "", "title": "The Journal of biological chemistry", "volume": "284", "year": 2009 }, "ssbd": { "database": [], "repository": [] }, "title": "Metabolite profiling reveals YihU as a novel hydroxybutyrate dehydrogenase for alternative succinic semialdehyde metabolism in Escherichia coli.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "We developed a multi-focus excitation coherent anti-Stokes Raman scattering (CARS) microscope using a microlens array scanner for real-time molecular imaging. Parallel exposure of a specimen with light from two highly controlled picosecond mode-locked lasers (jitter of 30 fs through an electronic low-pass filter with 150 Hz bandwidth, point-by-point wavelength scan within 300 ms) and parallel detection with an image sensor enabled real-time imaging. We demonstrated real-time CARS imaging of polystyrene beads (frame rate of 30 fps), a giant multi-lamellar vesicle of dipalmitoylphosphatidylcholine (frame rate of 10 fps), and living HeLa cells (frame rate of 10 fps).", "classifications": [ { "id": "Fujita", "label": "Group Fujita", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Takeo", "last_name": "Minamikawa", "name": null }, { "creator_type": "author", "first_name": "Mamoru", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Katsumasa", "last_name": "Fujita", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Kawata", "name": null }, { "creator_type": "author", "first_name": "Tsutomu", "last_name": "Araki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1364/oe.17.009526" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "19506600" } }, "mesh": [ { "descriptor": "Computer Systems", "descriptor_ui": "D003199", "major_topic": false }, { "descriptor": "Computer-Aided Design", "descriptor_ui": "D017076", "major_topic": false }, { "descriptor": "Equipment Design", "descriptor_ui": "D004867", "major_topic": false }, { "descriptor": "Equipment Failure Analysis", "descriptor_ui": "D019544", "major_topic": false }, { "descriptor": "Lenses", "descriptor_ui": "D007909", "major_topic": true }, { "descriptor": "Microscopy, Video", "descriptor_ui": "D018715", "major_topic": false }, { "descriptor": "Reproducibility of Results", "descriptor_ui": "D015203", "major_topic": false }, { "descriptor": "Sensitivity and Specificity", "descriptor_ui": "D012680", "major_topic": false }, { "descriptor": "Spectrum Analysis, Raman", "descriptor_ui": "D013059", "major_topic": false }, { "descriptor": "Tomography, Optical Coherence", "descriptor_ui": "D041623", "major_topic": false } ], "publication": { "conference_name": null, "date": "2009 Jun 8", "date_precision": "day", "issue": "12", "normalized_date": "2009-06-08", "pages": "9526-9536", "proceedings_title": null, "publisher": "", "title": "Optics express", "volume": "17", "year": 2009 }, "ssbd": { "database": [], "repository": [] }, "title": "Multi-focus excitation coherent anti-Stokes Raman scattering (CARS) microscopy and its applications for real-time imaging.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "A major bacterial alarmone, guanosine 3′,5′-bispyrophosphate (ppGpp), controls cellular growth under conditions of nutritional starvation. For most bacteria, intracellular ppGpp levels are tightly controlled by the synthesis/degradation cycle of RelA and SpoT activities. This study shows a novel ppGpp regulatory protein governing the cellular growth of Thermus thermophilus, Ndx8, a member of the Nudix pyrophosphatase family that degrades ppGpp to yield guanosine 3′,5′-bisphosphate. The ndx8-null mutant strain exhibited early stage growth arrest accompanied by the stationary phase-specific morphologies and global transcriptional modulation under nutritionally defined conditions. Several possible substrate compounds of Ndx8, which specifically accumulated in the ndx8 mutant cells, were identified by employing a capillary electrophoresis time-of-flight mass spectrometry-based metabolomics approach. Among them, the hydrolytic activity of Ndx8 for ppGpp was significant not only in vitro but also in vivo. Finally, the elimination of ppGpp synthetic activity suppressed the observed phenotype of the ndx8 mutation, suggesting that the function of Ndx8 as a growth regulator is involved in ppGpp accumulation, which is thought to act as a trigger of the growth phase transition. These results suggest a novel mechanism of ppGpp-mediated growth control by the functional relay between Ndx8 and SpoT activity as ppGpp scavengers.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Takushi", "last_name": "Ooga", "name": null }, { "creator_type": "author", "first_name": "Yoshiaki", "last_name": "Ohashi", "name": null }, { "creator_type": "author", "first_name": "Seiki", "last_name": "Kuramitsu", "name": null }, { "creator_type": "author", "first_name": "Yoshinori", "last_name": "Koyama", "name": null }, { "creator_type": "author", "first_name": "Masaru", "last_name": "Tomita", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Ryoji", "last_name": "Masui", "name": null } ], "identifiers": { "doi": { "normalized": "10.1074/jbc.m900582200" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "19346251" } }, "mesh": [ { "descriptor": "Bacterial Proteins", "descriptor_ui": "D001426", "major_topic": false }, { "descriptor": "Cell Division", "descriptor_ui": "D002455", "major_topic": false }, { "descriptor": "Conserved Sequence", "descriptor_ui": "D017124", "major_topic": false }, { "descriptor": "DNA Primers", "descriptor_ui": "D017931", "major_topic": false }, { "descriptor": "Guanosine Diphosphate", "descriptor_ui": "D006153", "major_topic": false }, { "descriptor": "Guanosine Tetraphosphate", "descriptor_ui": "D006159", "major_topic": false }, { "descriptor": "Kinetics", "descriptor_ui": "D007700", "major_topic": false }, { "descriptor": "Metabolome", "descriptor_ui": "D055442", "major_topic": false }, { "descriptor": "Oligonucleotide Array Sequence Analysis", "descriptor_ui": "D020411", "major_topic": false }, { "descriptor": "Phenotype", "descriptor_ui": "D010641", "major_topic": false }, { "descriptor": "Plasmids", "descriptor_ui": "D010957", "major_topic": false }, { "descriptor": "Polymerase Chain Reaction", "descriptor_ui": "D016133", "major_topic": false }, { "descriptor": "Pyrophosphatases", "descriptor_ui": "D011755", "major_topic": false }, { "descriptor": "Thermus thermophilus", "descriptor_ui": "D016963", "major_topic": false } ], "publication": { "conference_name": null, "date": "2009 Jun 5", "date_precision": "day", "issue": "23", "normalized_date": "2009-06-05", "pages": "15549-15556", "proceedings_title": null, "publisher": "", "title": "The Journal of Biological Chemistry", "volume": "284", "year": 2009 }, "ssbd": { "database": [], "repository": [] }, "title": "Degradation of ppGpp by Nudix Pyrophosphatase Modulates the Transition of Growth Phase in the Bacterium Thermus thermophilus*.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Most cancer cells predominantly produce energy by glycolysis rather than oxidative phosphorylation via the tricarboxylic acid (TCA) cycle, even in the presence of an adequate oxygen supply (Warburg effect). However, little has been reported regarding the direct measurements of global metabolites in clinical tumor tissues. Here, we applied capillary electrophoresis time-of-flight mass spectrometry, which enables comprehensive and quantitative analysis of charged metabolites, to simultaneously measure their levels in tumor and grossly normal tissues obtained from 16 colon and 12 stomach cancer patients. Quantification of 94 metabolites in colon and 95 metabolites in stomach involved in glycolysis, the pentose phosphate pathway, the TCA and urea cycles, and amino acid and nucleotide metabolisms resulted in the identification of several cancer-specific metabolic traits. Extremely low glucose and high lactate and glycolytic intermediate concentrations were found in both colon and stomach tumor tissues, which indicated enhanced glycolysis and thus confirmed the Warburg effect. Significant accumulation of all amino acids except glutamine in the tumors implied autophagic degradation of proteins and active glutamine breakdown for energy production, i.e., glutaminolysis. In addition, significant organ-specific differences were found in the levels of TCA cycle intermediates, which reflected the dependency of each tissue on aerobic respiration according to oxygen availability. The results uncovered unexpectedly poor nutritional conditions in the actual tumor microenvironment and showed that capillary electrophoresis coupled to mass spectrometry-based metabolomics, which is capable of quantifying the levels of energy metabolites in tissues, could be a powerful tool for the development of novel anticancer agents that target cancer-specific metabolism.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Akiyoshi", "last_name": "Hirayama", "name": null }, { "creator_type": "author", "first_name": "Kenjiro", "last_name": "Kami", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Sugimoto", "name": null }, { "creator_type": "author", "first_name": "Maki", "last_name": "Sugawara", "name": null }, { "creator_type": "author", "first_name": "Naoko", "last_name": "Toki", "name": null }, { "creator_type": "author", "first_name": "Hiroko", "last_name": "Onozuka", "name": null }, { "creator_type": "author", "first_name": "Taira", "last_name": "Kinoshita", "name": null }, { "creator_type": "author", "first_name": "Norio", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Ochiai", "name": null }, { "creator_type": "author", "first_name": "Masaru", "last_name": "Tomita", "name": null }, { "creator_type": "author", "first_name": "Hiroyasu", "last_name": "Esumi", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null } ], "identifiers": { "doi": { "normalized": "10.1158/0008-5472.can-08-4806" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "19458066" } }, "mesh": [ { "descriptor": "Citric Acid Cycle", "descriptor_ui": "D002952", "major_topic": false }, { "descriptor": "Colonic Neoplasms", "descriptor_ui": "D003110", "major_topic": false }, { "descriptor": "Electrophoresis, Capillary", "descriptor_ui": "D019075", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Glycolysis", "descriptor_ui": "D006019", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mass Spectrometry", "descriptor_ui": "D013058", "major_topic": false }, { "descriptor": "Metabolome", "descriptor_ui": "D055442", "major_topic": true }, { "descriptor": "Metabolomics", "descriptor_ui": "D055432", "major_topic": false }, { "descriptor": "Models, Biological", "descriptor_ui": "D008954", "major_topic": false }, { "descriptor": "Stomach Neoplasms", "descriptor_ui": "D013274", "major_topic": false } ], "publication": { "conference_name": null, "date": "2009 Jun 1", "date_precision": "day", "issue": "11", "normalized_date": "2009-06-01", "pages": "4918-4925", "proceedings_title": null, "publisher": "", "title": "Cancer research", "volume": "69", "year": 2009 }, "ssbd": { "database": [], "repository": [] }, "title": "Quantitative metabolome profiling of colon and stomach cancer microenvironment by capillary electrophoresis time-of-flight mass spectrometry.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: In response to viral infection, the innate immune system recognizes viral nucleic acids and then induces production of proinflammatory cytokines and type I interferons (IFNs). Toll-like receptor 7 (TLR7) and TLR9 detect viral RNA and DNA, respectively, in endosomal compartments, leading to the activation of nuclear factor kappaB (NF-kappaB) and IFN regulatory factors (IRFs) in plasmacytoid dendritic cells. During such TLR signaling, TNF receptor-associated factor 6 (TRAF6) is essential for the activation of NF-kappaB and the production of type I IFN. In contrast, RIG-like helicases (RLHs), cytosolic RNA sensors, are indispensable for antiviral responses in conventional dendritic cells, macrophages, and fibroblasts. However, the contribution of TRAF6 to the detection of cytosolic viral nucleic acids has been controversial, and the involvement of TRAF6 in IRF activation has not been adequately addressed. PRINCIPAL FINDINGS: Here we first show that TRAF6 plays a critical role in RLH signaling. The absence of TRAF6 resulted in enhanced viral replication and a significant reduction in the production of IL-6 and type I IFNs after infection with RNA virus. Activation of NF-kappaB and IRF7, but not that of IRF3, was significantly impaired during RLH signaling in the absence of TRAF6. TGFbeta-activated kinase 1 (TAK1) and MEKK3, whose activation by TRAF6 during TLR signaling is involved in NF-kappaB activation, were not essential for RLH-mediated NF-kappaB activation. We also demonstrate that TRAF6-deficiency impaired cytosolic DNA-induced antiviral responses, and this impairment was due to defective activation of NF-kappaB and IRF7. CONCLUSIONS/SIGNIFICANCE: Thus, TRAF6 mediates antiviral responses triggered by cytosolic viral DNA and RNA in a way that differs from that associated with TLR signaling. Given its essential role in signaling by various receptors involved in the acquired immune system, TRAF6 represents a key molecule in innate and antigen-specific immune responses against viral infection.", "classifications": [ { "id": "Yamamoto", "label": "Group Yamamoto", "parent": "Toyoshima", "type": "group" }, { "id": "Toyoshima", "label": "Team Toyoshima", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Jumpei", "last_name": "Taguchi", "name": null }, { "creator_type": "author", "first_name": "Yosuke", "last_name": "Yamada", "name": null }, { "creator_type": "author", "first_name": "Sho", "last_name": "Ohta", "name": null }, { "creator_type": "author", "first_name": "Fumie", "last_name": "Nakasuka", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Manabu", "last_name": "Ozawa", "name": null }, { "creator_type": "author", "first_name": "Yasuhiro", "last_name": "Yamada", "name": null }, { "creator_type": "author", "first_name": "Hiroyasu", "last_name": "Konno", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Kohsuke", "last_name": "Yamazaki", "name": null }, { "creator_type": "author", "first_name": "Jin", "last_name": "Gohda", "name": null }, { "creator_type": "author", "first_name": "Taishin", "last_name": "Akiyama", "name": null }, { "creator_type": "author", "first_name": "Kentaro", "last_name": "Semba", "name": null }, { "creator_type": "author", "first_name": "Hideo", "last_name": "Goto", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Toshiaki", "last_name": "Yujiri", "name": null }, { "creator_type": "author", "first_name": "Takahiko", "last_name": "Imai", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Kawaguchi", "name": null }, { "creator_type": "author", "first_name": "Bing", "last_name": "Su", "name": null }, { "creator_type": "author", "first_name": "Osamu", "last_name": "Takeuchi", "name": null }, { "creator_type": "author", "first_name": "Shizuo", "last_name": "Akira", "name": null }, { "creator_type": "author", "first_name": "Yasuko", "last_name": "Tsunetsugu-Yokota", "name": null }, { "creator_type": "author", "first_name": "Jun-ichiro", "last_name": "Inoue", "name": null } ], "identifiers": { "doi": { "normalized": "10.1371/journal.pone.0005674" }, "pmcid": { "normalized": "PMC2682567" }, "pmid": { "normalized": "19479062" } }, "mesh": [ { "descriptor": "Adaptor Proteins, Signal Transducing", "descriptor_ui": "D048868", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "Cytosol", "descriptor_ui": "D003600", "major_topic": false }, { "descriptor": "DEAD-box RNA Helicases", "descriptor_ui": "D053487", "major_topic": false }, { "descriptor": "DNA, Viral", "descriptor_ui": "D004279", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Immunity, Innate", "descriptor_ui": "D007113", "major_topic": false }, { "descriptor": "Interferon Regulatory Factor-3", "descriptor_ui": "D050838", "major_topic": false }, { "descriptor": "Interferon Regulatory Factor-7", "descriptor_ui": "D050839", "major_topic": false }, { "descriptor": "MAP Kinase Kinase Kinase 3", "descriptor_ui": "D048748", "major_topic": false }, { "descriptor": "MAP Kinase Kinase Kinase 7", "descriptor_ui": "D000099151", "major_topic": false }, { "descriptor": "MAP Kinase Kinase Kinases", "descriptor_ui": "D020930", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "NF-kappa B", "descriptor_ui": "D016328", "major_topic": false }, { "descriptor": "Protein Binding", "descriptor_ui": "D011485", "major_topic": false }, { "descriptor": "Protein Serine-Threonine Kinases", "descriptor_ui": "D017346", "major_topic": false }, { "descriptor": "RNA Viruses", "descriptor_ui": "D012328", "major_topic": false }, { "descriptor": "RNA, Viral", "descriptor_ui": "D012367", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "TNF Receptor-Associated Factor 6", "descriptor_ui": "D048029", "major_topic": false } ], "publication": { "conference_name": null, "date": "2009 May 25", "date_precision": "day", "issue": "5", "normalized_date": "2009-05-25", "pages": "e5674", "proceedings_title": null, "publisher": "", "title": "PloS one", "volume": "4", "year": 2009 }, "ssbd": { "database": [], "repository": [] }, "title": "TRAF6 establishes innate immune responses by activating NF-kappaB and IRF7 upon sensing cytosolic viral RNA and DNA.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Canonical transient receptor potential (TRPC) channels control influxes of Ca2+ and other cations that induce diverse cellular processes upon stimulation of plasma membrane receptors coupled to phospholipase C (PLC). Invention of subtype-specific inhibitors for TRPCs is crucial for distinction of respective TRPC channels that play particular physiological roles in native systems. Here, we identify a pyrazole compound (Pyr3), which selectively inhibits TRPC3 channels. Structure-function relationship studies of pyrazole compounds showed that the trichloroacrylic amide group is important for the TRPC3 selectivity of Pyr3. Electrophysiological and photoaffinity labeling experiments reveal a direct action of Pyr3 on the TRPC3 protein. In DT40 B lymphocytes, Pyr3 potently eliminated the Ca2+ influx-dependent PLC translocation to the plasma membrane and late oscillatory phase of B cell receptor-induced Ca2+ response. Moreover, Pyr3 attenuated activation of nuclear factor of activated T cells, a Ca2+-dependent transcription factor, and hypertrophic growth in rat neonatal cardiomyocytes, and in vivo pressure overload-induced cardiac hypertrophy in mice. These findings on important roles of native TRPC3 channels are strikingly consistent with previous genetic studies. Thus, the TRPC3-selective inhibitor Pyr3 is a powerful tool to study in vivo function of TRPC3, suggesting a pharmaceutical potential of Pyr3 in treatments of TRPC3-related diseases such as cardiac hypertrophy.", "classifications": [ { "id": "Nishida", "label": "Group Nishida", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Shigeki", "last_name": "Kiyonaka", "name": null }, { "creator_type": "author", "first_name": "Kenta", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Motohiro", "last_name": "Nishida", "name": null }, { "creator_type": "author", "first_name": "Kazuhiro", "last_name": "Mio", "name": null }, { "creator_type": "author", "first_name": "Takuro", "last_name": "Numaga", "name": null }, { "creator_type": "author", "first_name": "Yuichi", "last_name": "Sawaguchi", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Minoru", "last_name": "Wakamori", "name": null }, { "creator_type": "author", "first_name": "Emiko", "last_name": "Mori", "name": null }, { "creator_type": "author", "first_name": "Tomohiro", "last_name": "Numata", "name": null }, { "creator_type": "author", "first_name": "Masakazu", "last_name": "Ishii", "name": null }, { "creator_type": "author", "first_name": "Hiroki", "last_name": "Takemoto", "name": null }, { "creator_type": "author", "first_name": "Akio", "last_name": "Ojida", "name": null }, { "creator_type": "author", "first_name": "Kenta", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Aya", "last_name": "Uemura", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Kurose", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Morii", "name": null }, { "creator_type": "author", "first_name": "Tsutomu", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Yoji", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Chikara", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Itaru", "last_name": "Hamachi", "name": null }, { "creator_type": "author", "first_name": "Yasuo", "last_name": "Mori", "name": null } ], "identifiers": { "doi": { "normalized": "10.1073/pnas.0808793106" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "19289841" } }, "mesh": [ { "descriptor": "Amides", "descriptor_ui": "D000577", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "B-Lymphocytes", "descriptor_ui": "D001402", "major_topic": false }, { "descriptor": "Calcium", "descriptor_ui": "D002118", "major_topic": false }, { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "Hypertrophy", "descriptor_ui": "D006984", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Myocytes, Cardiac", "descriptor_ui": "D032383", "major_topic": false }, { "descriptor": "NFATC Transcription Factors", "descriptor_ui": "D050778", "major_topic": false }, { "descriptor": "Protein Transport", "descriptor_ui": "D021381", "major_topic": false }, { "descriptor": "Pyrazoles", "descriptor_ui": "D011720", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Structure-Activity Relationship", "descriptor_ui": "D013329", "major_topic": false }, { "descriptor": "TRPC Cation Channels", "descriptor_ui": "D050052", "major_topic": false }, { "descriptor": "Type C Phospholipases", "descriptor_ui": "D010738", "major_topic": false } ], "publication": { "conference_name": null, "date": "2009 Mar 31", "date_precision": "day", "issue": "13", "normalized_date": "2009-03-31", "pages": "5400-5405", "proceedings_title": null, "publisher": "", "title": "Proceedings of the National Academy of Sciences of the United States of America", "volume": "106", "year": 2009 }, "ssbd": { "database": [], "repository": [] }, "title": "Selective and direct inhibition of TRPC3 channels underlies biological activities of a pyrazole compound.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Protein modification by small ubiquitin-related modifier proteins (SUMOs) controls diverse cellular functions. Dysregulation of SUMOylation or deSUMOylation processes has been implicated in the development of cancer and neurodegenerative diseases. However, no small-molecule inhibiting protein SUMOylation has been reported so far. Here, we report inhibition of SUMOylation by ginkgolic acid and its analog, anacardic acid. Ginkgolic acid and anacardic acid inhibit protein SUMOylation both in vitro and in vivo without affecting in vivo ubiquitination. Binding assays with a fluorescently labeled probe showed that ginkgolic acid directly binds E1 and inhibits the formation of the E1-SUMO intermediate. These studies will provide not only a useful tool for investigating the roles of SUMO conjugations in a variety of pathways in cells, but also a basis for the development of drugs targeted against diseases involving aberrant SUMOylation.", "classifications": [ { "id": "Sodeoka", "label": "Group Sodeoka", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Isao", "last_name": "Fukuda", "name": null }, { "creator_type": "author", "first_name": "Akihiro", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Go", "last_name": "Hirai", "name": null }, { "creator_type": "author", "first_name": "Shinichi", "last_name": "Nishimura", "name": null }, { "creator_type": "author", "first_name": "Hisashi", "last_name": "Kawasaki", "name": null }, { "creator_type": "author", "first_name": "Hisato", "last_name": "Saitoh", "name": null }, { "creator_type": "author", "first_name": "Ken-Ichi", "last_name": "Kimura", "name": null }, { "creator_type": "author", "first_name": "Mikiko", "last_name": "Sodeoka", "name": null }, { "creator_type": "author", "first_name": "Minoru", "last_name": "Yoshida", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.chembiol.2009.01.009" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "19246003" } }, "mesh": [ { "descriptor": "Anacardic Acids", "descriptor_ui": "D048729", "major_topic": false }, { "descriptor": "Ginkgo biloba", "descriptor_ui": "D020441", "major_topic": false }, { "descriptor": "Plant Extracts", "descriptor_ui": "D010936", "major_topic": false }, { "descriptor": "Plant Leaves", "descriptor_ui": "D018515", "major_topic": false }, { "descriptor": "Protein Binding", "descriptor_ui": "D011485", "major_topic": false }, { "descriptor": "Salicylates", "descriptor_ui": "D012459", "major_topic": false }, { "descriptor": "Small Molecule Libraries", "descriptor_ui": "D054852", "major_topic": false }, { "descriptor": "Small Ubiquitin-Related Modifier Proteins", "descriptor_ui": "D025841", "major_topic": false }, { "descriptor": "Structure-Activity Relationship", "descriptor_ui": "D013329", "major_topic": false }, { "descriptor": "Ubiquitination", "descriptor_ui": "D054875", "major_topic": false } ], "publication": { "conference_name": null, "date": "2009 Feb 27", "date_precision": "day", "issue": "2", "normalized_date": "2009-02-27", "pages": "133-140", "proceedings_title": null, "publisher": "", "title": "Chemistry & biology", "volume": "16", "year": 2009 }, "ssbd": { "database": [], "repository": [] }, "title": "Ginkgolic acid inhibits protein SUMOylation by blocking formation of the E1-SUMO intermediate.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Dietary restriction is the most effective and reproducible intervention to extend lifespan in divergent species. In mammals, two regimens of dietary restriction, intermittent fasting (IF) and chronic caloric restriction, have proven to extend lifespan and reduce the incidence of age-related disorders. An important characteristic of IF is that it can increase lifespan even when there is little or no overall decrease in calorie intake. The molecular mechanisms underlying IF-induced longevity, however, remain largely unknown. Here we establish an IF regimen that effectively extends the lifespan of Caenorhabditis elegans, and show that the low molecular weight GTPase RHEB-1 has a dual role in lifespan regulation; RHEB-1 is required for the IF-induced longevity, whereas inhibition of RHEB-1 mimics the caloric-restriction effects. RHEB-1 exerts its effects in part by the insulin/insulin growth factor (IGF)-like signalling effector DAF-16 in IF. Our analyses demonstrate that most fasting-induced upregulated genes require RHEB-1 function for their induction, and that RHEB-1 and TOR signalling are required for the fasting-induced downregulation of an insulin-like peptide, INS-7. These findings identify the essential role of signalling by RHEB-1 in IF-induced longevity and gene expression changes, and suggest a molecular link between the IF-induced longevity and the insulin/IGF-like signalling pathway.", "classifications": [ { "id": "Yamamoto", "label": "Group Yamamoto", "parent": "Toyoshima", "type": "group" }, { "id": "Toyoshima", "label": "Team Toyoshima", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Sakiko", "last_name": "Honjoh", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Masaharu", "last_name": "Uno", "name": null }, { "creator_type": "author", "first_name": "Eisuke", "last_name": "Nishida", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/nature07583" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "19079239" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Animals, Genetically Modified", "descriptor_ui": "D030801", "major_topic": false }, { "descriptor": "Caenorhabditis elegans", "descriptor_ui": "D017173", "major_topic": false }, { "descriptor": "Caenorhabditis elegans Proteins", "descriptor_ui": "D029742", "major_topic": false }, { "descriptor": "Caloric Restriction", "descriptor_ui": "D031204", "major_topic": false }, { "descriptor": "Fasting", "descriptor_ui": "D005215", "major_topic": false }, { "descriptor": "Forkhead Transcription Factors", "descriptor_ui": "D051858", "major_topic": false }, { "descriptor": "Gene Expression Regulation", "descriptor_ui": "D005786", "major_topic": false }, { "descriptor": "Insulin", "descriptor_ui": "D007328", "major_topic": false }, { "descriptor": "Longevity", "descriptor_ui": "D008136", "major_topic": false }, { "descriptor": "Monomeric GTP-Binding Proteins", "descriptor_ui": "D020559", "major_topic": false }, { "descriptor": "Oligonucleotide Array Sequence Analysis", "descriptor_ui": "D020411", "major_topic": false }, { "descriptor": "Peptide Hormones", "descriptor_ui": "D036361", "major_topic": false }, { "descriptor": "Ras Homolog Enriched in Brain Protein", "descriptor_ui": "D000076205", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": true }, { "descriptor": "Somatomedins", "descriptor_ui": "D013002", "major_topic": false }, { "descriptor": "Transcription Factors", "descriptor_ui": "D014157", "major_topic": false } ], "publication": { "conference_name": null, "date": "2009 Feb 5", "date_precision": "day", "issue": "7230", "normalized_date": "2009-02-05", "pages": "726-730", "proceedings_title": null, "publisher": "", "title": "Nature", "volume": "457", "year": 2009 }, "ssbd": { "database": [], "repository": [] }, "title": "Signalling through RHEB-1 mediates intermittent fasting-induced longevity in C. elegans.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Central carbon metabolism is a basic and exhaustively analyzed pathway. However, the intrinsic robustness of the pathway might still conceal uncharacterized reactions. To test this hypothesis, we constructed systematic multiple-knockout mutants involved in central carbon catabolism in Escherichia coli and tested their growth under 12 different nutrient conditions. Differences between in silico predictions and experimental growth indicated that unreported reactions existed within this extensively analyzed metabolic network. These putative reactions were then confirmed by metabolome analysis and in vitro enzymatic assays. Novel reactions regarding the breakdown of sedoheptulose-7-phosphate to erythrose-4-phosphate and dihydroxyacetone phosphate were observed in transaldolase-deficient mutants, without any noticeable changes in gene expression. These reactions, triggered by an accumulation of sedoheptulose-7-phosphate, were catalyzed by the universally conserved glycolytic enzymes ATP-dependent phosphofructokinase and aldolase. The emergence of an alternative pathway not requiring any changes in gene expression, but rather relying on the accumulation of an intermediate metabolite may be a novel mechanism mediating the robustness of these metabolic networks.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Kenji", "last_name": "Nakahigashi", "name": null }, { "creator_type": "author", "first_name": "Yoshihiro", "last_name": "Toya", "name": null }, { "creator_type": "author", "first_name": "Nobuyoshi", "last_name": "Ishii", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Miki", "last_name": "Hasegawa", "name": null }, { "creator_type": "author", "first_name": "Hisami", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Takai", "name": null }, { "creator_type": "author", "first_name": "Masayuki", "last_name": "Honma", "name": null }, { "creator_type": "author", "first_name": "Hirotada", "last_name": "Mori", "name": null }, { "creator_type": "author", "first_name": "Masaru", "last_name": "Tomita", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/msb.2009.65" }, "pmcid": { "normalized": "PMC2758719" }, "pmid": { "normalized": "19756045" } }, "mesh": [ { "descriptor": "Carbon", "descriptor_ui": "D002244", "major_topic": false }, { "descriptor": "Computer Simulation", "descriptor_ui": "D003198", "major_topic": false }, { "descriptor": "Culture Media", "descriptor_ui": "D003470", "major_topic": false }, { "descriptor": "Dihydroxyacetone Phosphate", "descriptor_ui": "D004099", "major_topic": false }, { "descriptor": "Escherichia coli", "descriptor_ui": "D004926", "major_topic": false }, { "descriptor": "Escherichia coli Proteins", "descriptor_ui": "D029968", "major_topic": false }, { "descriptor": "Gene Expression Profiling", "descriptor_ui": "D020869", "major_topic": false }, { "descriptor": "Gene Knockout Techniques", "descriptor_ui": "D055786", "major_topic": false }, { "descriptor": "Metabolic Networks and Pathways", "descriptor_ui": "D053858", "major_topic": false }, { "descriptor": "Metabolome", "descriptor_ui": "D055442", "major_topic": false }, { "descriptor": "Models, Biological", "descriptor_ui": "D008954", "major_topic": false }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": false }, { "descriptor": "Phenotype", "descriptor_ui": "D010641", "major_topic": false }, { "descriptor": "Sugar Phosphates", "descriptor_ui": "D013403", "major_topic": false }, { "descriptor": "Systems Biology", "descriptor_ui": "D049490", "major_topic": false }, { "descriptor": "Transaldolase", "descriptor_ui": "D014153", "major_topic": false } ], "publication": { "conference_name": null, "date": "2009", "date_precision": "year", "issue": "", "normalized_date": "2009", "pages": "306", "proceedings_title": null, "publisher": "", "title": "Molecular systems biology", "volume": "5", "year": 2009 }, "ssbd": { "database": [], "repository": [] }, "title": "Systematic phenome analysis of Escherichia coli multiple-knockout mutants reveals hidden reactions in central carbon metabolism.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Let the dominos fall: Synthesis of the complex DFGH ring system of the title compounds has been accomplished. The approach features simple treatment of the key intermediate with a Bronsted base to afford the tetracyclic cage-shaped target in one pot through a four-step domino transformation (see scheme; Mc = monochloromesylate, MOM = methoxymethyl).", "classifications": [ { "id": "Sodeoka", "label": "Group Sodeoka", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Megumi", "last_name": "Ohkubo", "name": null }, { "creator_type": "author", "first_name": "Go", "last_name": "Hirai", "name": null }, { "creator_type": "author", "first_name": "Mikiko", "last_name": "Sodeoka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/anie.200900634" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "19378305" } }, "mesh": [ { "descriptor": "Molecular Structure", "descriptor_ui": "D015394", "major_topic": false }, { "descriptor": "Oxygen", "descriptor_ui": "D010100", "major_topic": false }, { "descriptor": "Secosteroids", "descriptor_ui": "D012632", "major_topic": false } ], "publication": { "conference_name": null, "date": "2009", "date_precision": "year", "issue": "21", "normalized_date": "2009", "pages": "3862-3866", "proceedings_title": null, "publisher": "", "title": "Angewandte Chemie (International ed. in English)", "volume": "48", "year": 2009 }, "ssbd": { "database": [], "repository": [] }, "title": "Synthesis of the DFGH ring system of type B physalins: highly oxygenated, cage-shaped molecules.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Palladium can tailor fullerenes: Palladium catalysts enable a number of C-H bond transformations of organo(hydro)fullerene. In addition to anticipated coupling reactions (C-H bond allylation and arylation), an unexpected new C-H bond dimerization reaction and C-C bond-cleavage reaction were also uncovered.", "classifications": [ { "id": "Nanbo", "label": "Group Nanbo", "parent": "Tsuchiya", "type": "group" }, { "id": "Tsuchiya", "label": "Team Tsuchiya", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Masakazu", "last_name": "Nambo", "name": null }, { "creator_type": "author", "first_name": "Kenichiro", "last_name": "Itami", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/chem.200900022" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "19229928" } }, "mesh": [], "publication": { "conference_name": null, "date": "2009", "date_precision": "year", "issue": "19", "normalized_date": "2009", "pages": "4760-4764", "proceedings_title": null, "publisher": "", "title": "Chemistry (Weinheim an der Bergstrasse, Germany)", "volume": "15", "year": 2009 }, "ssbd": { "database": [], "repository": [] }, "title": "Palladium-catalyzed carbon-carbon bond formation and cleavage of organo(hydro)fullerenes.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Chicken ovalbumin upstream promoter transcription factors (COUP-TF) are orphan members of the nuclear receptor superfamily and consist of COUP-TFI and COUP-TFII. COUP-TFI was reported to be overexpressed in human breast cancer and to promote estrogen-independent transcriptional activity of estrogen receptor alpha. COUP-TFII, however, has not been examined in the breast. Therefore, we carried out immunohistochemical analysis of COUP-TFII in human breast cancer in order to clarify its biological and clinical significance. We immunolocalized COUP-TFII in 119 human breast cancers and correlated the findings with various clinicopathological parameters. Fifty-nine percent of the cases were immunohistochemically positive for COUP-TFII. COUP-TFII positivity was correlated with poor clinical outcome, and a statistically significant correlation was detected between COUP-TFII and the following clinicopathological parameters: clinical stage, lymph node status, histological grade, and estrogen receptor alpha status. In addition, short interfering RNA-mediated knockdown of COUP-TFII in the breast carcinoma cell line MCF-7 decreased the level of vascular endothelial growth factor-C mRNA expression, which is a known inducer of lymphangiogenesis and lymph node metastasis. These results suggest that COUP-TFII is involved in the development of advanced human breast cancer.", "classifications": [ { "id": "Suzuki", "label": "Group Suzuki", "parent": "Takekawa", "type": "group" }, { "id": "Takekawa", "label": "Team Takekawa", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Shuji", "last_name": "Nagasaki", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Yasuhiro", "last_name": "Miki", "name": null }, { "creator_type": "author", "first_name": "Jun-ichi", "last_name": "Akahira", "name": null }, { "creator_type": "author", "first_name": "Hirotaka", "last_name": "Shibata", "name": null }, { "creator_type": "author", "first_name": "Takanori", "last_name": "Ishida", "name": null }, { "creator_type": "author", "first_name": "Noriaki", "last_name": "Ohuchi", "name": null }, { "creator_type": "author", "first_name": "Hironobu", "last_name": "Sasano", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/j.1349-7006.2008.01078.x" }, "pmcid": { "normalized": "PMC11158707" }, "pmid": { "normalized": "19154418" } }, "mesh": [ { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Breast Neoplasms", "descriptor_ui": "D001943", "major_topic": false }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "COUP Transcription Factor II", "descriptor_ui": "D051837", "major_topic": false }, { "descriptor": "Estrogen Receptor alpha", "descriptor_ui": "D047628", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Fluorescent Antibody Technique, Indirect", "descriptor_ui": "D019084", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Immunohistochemistry", "descriptor_ui": "D007150", "major_topic": false }, { "descriptor": "Ki-67 Antigen", "descriptor_ui": "D019394", "major_topic": false }, { "descriptor": "Lymphangiogenesis", "descriptor_ui": "D042583", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "RNA, Messenger", "descriptor_ui": "D012333", "major_topic": false }, { "descriptor": "RNA, Small Interfering", "descriptor_ui": "D034741", "major_topic": false }, { "descriptor": "Vascular Endothelial Growth Factor C", "descriptor_ui": "D042582", "major_topic": false }, { "descriptor": "Young Adult", "descriptor_ui": "D055815", "major_topic": false } ], "publication": { "conference_name": null, "date": "2009 Apr", "date_precision": "unknown", "issue": "4", "normalized_date": null, "pages": "639-645", "proceedings_title": null, "publisher": "", "title": "Cancer science", "volume": "100", "year": 2009 }, "ssbd": { "database": [], "repository": [] }, "title": "Chicken ovalbumin upstream promoter transcription factor II in human breast carcinoma: possible regulator of lymphangiogenesis via vascular endothelial growth factor-C expression.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Hypertension in patients with chronic kidney disease (CKD) strongly associates with cardiovascular events. Among patients with CKD, reducing the accumulation of uremic toxins may protect against the development of hypertension and progression of renal damage, but there are no established therapies to accomplish this. Here, overexpression of human kidney-specific organic anion transporter SLCO4C1 in rat kidney reduced hypertension, cardiomegaly, and inflammation in the setting of renal failure. In addition, SLCO4C1 overexpression decreased plasma levels of the uremic toxins guanidino succinate, asymmetric dimethylarginine, and the newly identified trans-aconitate. We found that xenobiotic responsive element core motifs regulate SLCO4C1 transcription, and various statins, which act as inducers of nuclear aryl hydrocarbon receptors, upregulate SLCO4C1 transcription. Pravastatin, which is cardioprotective, increased the clearance of asymmetric dimethylarginine and trans-aconitate in renal failure. These data suggest that drugs that upregulate SLCO4C1 may have therapeutic potential for patients with CKD.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Takafumi", "last_name": "Toyohara", "name": null }, { "creator_type": "author", "first_name": "Takehiro", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Ryo", "last_name": "Morimoto", "name": null }, { "creator_type": "author", "first_name": "Yasutoshi", "last_name": "Akiyama", "name": null }, { "creator_type": "author", "first_name": "Tomokazu", "last_name": "Souma", "name": null }, { "creator_type": "author", "first_name": "Hiromi O.", "last_name": "Shiwaku", "name": null }, { "creator_type": "author", "first_name": "Yoichi", "last_name": "Takeuchi", "name": null }, { "creator_type": "author", "first_name": "Eikan", "last_name": "Mishima", "name": null }, { "creator_type": "author", "first_name": "Michiaki", "last_name": "Abe", "name": null }, { "creator_type": "author", "first_name": "Masayuki", "last_name": "Tanemoto", "name": null }, { "creator_type": "author", "first_name": "Satohiro", "last_name": "Masuda", "name": null }, { "creator_type": "author", "first_name": "Hiroaki", "last_name": "Kawano", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Maemura", "name": null }, { "creator_type": "author", "first_name": "Masaaki", "last_name": "Nakayama", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Tsuyoshi", "last_name": "Mikkaichi", "name": null }, { "creator_type": "author", "first_name": "Hiroaki", "last_name": "Yamaguchi", "name": null }, { "creator_type": "author", "first_name": "Shigefumi", "last_name": "Fukui", "name": null }, { "creator_type": "author", "first_name": "Yoshihiro", "last_name": "Fukumoto", "name": null }, { "creator_type": "author", "first_name": "Hiroaki", "last_name": "Shimokawa", "name": null }, { "creator_type": "author", "first_name": "Ken-ichi", "last_name": "Inui", "name": null }, { "creator_type": "author", "first_name": "Tetsuya", "last_name": "Terasaki", "name": null }, { "creator_type": "author", "first_name": "Junichi", "last_name": "Goto", "name": null }, { "creator_type": "author", "first_name": "Sadayoshi", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Takanori", "last_name": "Hishinuma", "name": null }, { "creator_type": "author", "first_name": "Isabelle", "last_name": "Rubera", "name": null }, { "creator_type": "author", "first_name": "Michel", "last_name": "Tauc", "name": null }, { "creator_type": "author", "first_name": "Yoshiaki", "last_name": "Fujii-Kuriyama", "name": null }, { "creator_type": "author", "first_name": "Hikaru", "last_name": "Yabuuchi", "name": null }, { "creator_type": "author", "first_name": "Yoshinori", "last_name": "Moriyama", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Takaaki", "last_name": "Abe", "name": null } ], "identifiers": { "doi": { "normalized": "10.1681/asn.2009070696" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "19875811" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Animals, Genetically Modified", "descriptor_ui": "D030801", "major_topic": false }, { "descriptor": "Base Sequence", "descriptor_ui": "D001483", "major_topic": false }, { "descriptor": "Biological Transport, Active", "descriptor_ui": "D001693", "major_topic": false }, { "descriptor": "DNA", "descriptor_ui": "D004247", "major_topic": false }, { "descriptor": "Gene Expression", "descriptor_ui": "D015870", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Hydroxymethylglutaryl-CoA Reductase Inhibitors", "descriptor_ui": "D019161", "major_topic": false }, { "descriptor": "Hypertension", "descriptor_ui": "D006973", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Models, Biological", "descriptor_ui": "D008954", "major_topic": false }, { "descriptor": "Molecular Sequence Data", "descriptor_ui": "D008969", "major_topic": false }, { "descriptor": "Nephritis", "descriptor_ui": "D009393", "major_topic": false }, { "descriptor": "Organic Anion Transporters", "descriptor_ui": "D027361", "major_topic": false }, { "descriptor": "Promoter Regions, Genetic", "descriptor_ui": "D011401", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Recombinant Proteins", "descriptor_ui": "D011994", "major_topic": false }, { "descriptor": "Renal Insufficiency, Chronic", "descriptor_ui": "D051436", "major_topic": false }, { "descriptor": "Toxins, Biological", "descriptor_ui": "D014118", "major_topic": false }, { "descriptor": "Uremia", "descriptor_ui": "D014511", "major_topic": false } ], "publication": { "conference_name": null, "date": "2009 Dec", "date_precision": "unknown", "issue": "12", "normalized_date": null, "pages": "2546-2555", "proceedings_title": null, "publisher": "", "title": "Journal of the American Society of Nephrology : JASN", "volume": "20", "year": 2009 }, "ssbd": { "database": [], "repository": [] }, "title": "SLCO4C1 Transporter Eliminates Uremic Toxins and Attenuates Hypertension and Renal Inflammation.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Amphotericin B (AMB) is one of the most effective antifungal agents; however, its use is often limited by the occurrence of adverse events, especially nephrotoxicity. The present study was designed to determine the possible mechanisms underlying the nephrotoxic action of AMB. The exposure of a porcine proximal renal tubular cell line (LLC-PK1 cells) to AMB caused cell injury, as assessed by mitochondrial enzyme activity, the leakage of lactate dehydrogenase, and tissue ATP depletion. Propidium iodide uptake was enhanced, while terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling was not affected by AMB, suggesting a lack of involvement of apoptosis in AMB-induced cell injury. The cell injury was inhibited by the depletion of membrane cholesterol with methyl-beta-cyclodextrin, which lowered the extracellular Na(+) concentration or the chelation of intracellular Ca(2+). The rise in the intracellular Ca(2+) concentration may be mediated through the activation of the ryanodine receptor (RyR) on the endoplasmic reticulum and the mitochondrial Na(+)-Ca(2+) exchanger, since cell injury was attenuated by dantrolene (an RyR antagonist) and CGP37157 (an Na(+)-Ca(2+) exchanger inhibitor). Moreover, AMB-induced cell injury was reversed by PD169316 (a p38 mitogen-activated protein [MAP] kinase inhibitor), c-Jun N-terminal kinase inhibitor II, and PD98059 (a MEK1/2 inhibitor). The phosphorylations of these MAP kinases were enhanced by AMB in a calcium-independent manner, suggesting the involvement of MAP kinases in AMB-induced cell injury. These findings suggest that Na(+) entry through membrane pores formed by the association of AMB with membrane cholesterol leads to the activation of MAP kinases and the elevation of the intracellular Ca(2+) concentration, leading to renal tubular cell injury.", "classifications": [ { "id": "Nishida", "label": "Group Nishida", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Takahisa", "last_name": "Yano", "name": null }, { "creator_type": "author", "first_name": "Yoshinori", "last_name": "Itoh", "name": null }, { "creator_type": "author", "first_name": "Eiko", "last_name": "Kawamura", "name": null }, { "creator_type": "author", "first_name": "Asuka", "last_name": "Maeda", "name": null }, { "creator_type": "author", "first_name": "Nobuaki", "last_name": "Egashira", "name": null }, { "creator_type": "author", "first_name": "Motohiro", "last_name": "Nishida", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Kurose", "name": null }, { "creator_type": "author", "first_name": "Ryozo", "last_name": "Oishi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1128/aac.01137-08" }, "pmcid": { "normalized": "PMC2663073" }, "pmid": { "normalized": "19139282" } }, "mesh": [ { "descriptor": "Adenosine Triphosphate", "descriptor_ui": "D000255", "major_topic": false }, { "descriptor": "Amphotericin B", "descriptor_ui": "D000666", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Antifungal Agents", "descriptor_ui": "D000935", "major_topic": false }, { "descriptor": "Calcium", "descriptor_ui": "D002118", "major_topic": false }, { "descriptor": "Cholesterol", "descriptor_ui": "D002784", "major_topic": false }, { "descriptor": "Endoplasmic Reticulum", "descriptor_ui": "D004721", "major_topic": false }, { "descriptor": "Extracellular Signal-Regulated MAP Kinases", "descriptor_ui": "D048049", "major_topic": false }, { "descriptor": "Kidney Tubules", "descriptor_ui": "D007684", "major_topic": false }, { "descriptor": "LLC-PK1 Cells", "descriptor_ui": "D018374", "major_topic": false }, { "descriptor": "MAP Kinase Signaling System", "descriptor_ui": "D020935", "major_topic": false }, { "descriptor": "Mitochondria", "descriptor_ui": "D008928", "major_topic": false }, { "descriptor": "Sodium", "descriptor_ui": "D012964", "major_topic": false }, { "descriptor": "Swine", "descriptor_ui": "D013552", "major_topic": false } ], "publication": { "conference_name": null, "date": "2009 Apr", "date_precision": "unknown", "issue": "4", "normalized_date": null, "pages": "1420-1426", "proceedings_title": null, "publisher": "", "title": "Antimicrobial agents and chemotherapy", "volume": "53", "year": 2009 }, "ssbd": { "database": [], "repository": [] }, "title": "Amphotericin B-induced renal tubular cell injury is mediated by Na+ Influx through ion-permeable pores and subsequent activation of mitogen-activated protein kinases and elevation of intracellular Ca2+ concentration.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Carbon monoxide (CO) is a stress-inducible gas generated by heme oxygenase (HO) eliciting adaptive responses against toxicants; however, mechanisms for its reception remain unknown. Serendipitous observation in metabolome analysis in CO-overproducing livers suggested roles of cystathionine beta-synthase (CBS) that rate-limits transsulfuration pathway and H(2)S generation, for the gas-responsive receptor. Studies using recombinant CBS indicated that CO binds to the prosthetic heme, stabilizing 6-coordinated CO-Fe(II)-histidine complex to block the activity, whereas nitric oxide (NO) forms 5-coordinated structure without inhibiting it. The CO-overproducing livers down-regulated H(2)S to stimulate HCO(3) (-)-dependent choleresis: these responses were attenuated by blocking HO or by donating H(2)S. Livers of heterozygous CBS knockout mice neither down-regulated H(2)S nor exhibited the choleresis while overproducing CO. In the mouse model of estradiol-induced cholestasis, CO overproduction by inducing HO-1 significantly improved the bile output through stimulating HCO(3) (-) excretion; such a choleretic response did not occur in the knockout mice. CONCLUSION: Results collected from metabolome analyses suggested that CBS serves as a CO-sensitive modulator of H(2)S to support biliary excretion, shedding light on a putative role of the enzyme for stress-elicited adaptive response against bile-dependent detoxification processes.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Tsunehiro", "last_name": "Shintani", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Iwabuchi", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Yuichiro", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Takehiro", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Naoharu", "last_name": "Takano", "name": null }, { "creator_type": "author", "first_name": "Takako", "last_name": "Hishiki", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Ueno", "name": null }, { "creator_type": "author", "first_name": "Satsuki", "last_name": "Ikeda", "name": null }, { "creator_type": "author", "first_name": "Tadayuki", "last_name": "Sakuragawa", "name": null }, { "creator_type": "author", "first_name": "Kazuo", "last_name": "Ishikawa", "name": null }, { "creator_type": "author", "first_name": "Nobuhito", "last_name": "Goda", "name": null }, { "creator_type": "author", "first_name": "Yuko", "last_name": "Kitagawa", "name": null }, { "creator_type": "author", "first_name": "Mayumi", "last_name": "Kajimura", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Matsumoto", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Suematsu", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/hep.22604" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "19085910" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Bile", "descriptor_ui": "D001646", "major_topic": false }, { "descriptor": "Carbon Monoxide", "descriptor_ui": "D002248", "major_topic": false }, { "descriptor": "Cystathionine beta-Synthase", "descriptor_ui": "D003541", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Metabolome", "descriptor_ui": "D055442", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false } ], "publication": { "conference_name": null, "date": "2009 Jan", "date_precision": "unknown", "issue": "1", "normalized_date": null, "pages": "141-150", "proceedings_title": null, "publisher": "", "title": "Hepatology (Baltimore, Md.)", "volume": "49", "year": 2009 }, "ssbd": { "database": [], "repository": [] }, "title": "Cystathionine beta-synthase as a carbon monoxide-sensitive regulator of bile excretion.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Most molecular imaging technologies require exogenous probes and may have some influence on the intracellular dynamics of target molecules. In contrast, Raman scattering light measurement can identify biomolecules in their innate state without application of staining methods. Our aim was to analyze intracellular dynamics of topoisomerase I inhibitor, CPT-11, by using slit-scanning confocal Raman microscopy, which can take Raman images with high temporal and spatial resolution. We could acquire images of the intracellular distribution of CPT-11 and its metabolite SN-38 within several minutes without use of any exogenous tags. Change of subcellular drug localization after treatment could be assessed by Raman imaging. We also showed intracellular conversion from CPT-11 to SN-38 using Raman spectra. The study shows the feasibility of using slit-scanning confocal Raman microscopy for the non-labeling evaluation of the intracellular dynamics of CPT-11 with high temporal and spatial resolution. We conclude that Raman spectromicroscopic imaging is useful for pharmacokinetic studies of anticancer drugs in living cells.", "classifications": [ { "id": "Tanaka", "label": "Group Tanaka", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yoshinori", "last_name": "Harada", "name": null }, { "creator_type": "author", "first_name": "Ping", "last_name": "Dai", "name": null }, { "creator_type": "author", "first_name": "Yoshihisa", "last_name": "Yamaoka", "name": null }, { "creator_type": "author", "first_name": "Mitsugu", "last_name": "Ogawa", "name": null }, { "creator_type": "author", "first_name": "Hideo", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Kazuto", "last_name": "Nosaka", "name": null }, { "creator_type": "author", "first_name": "Kenichi", "last_name": "Akaji", "name": null }, { "creator_type": "author", "first_name": "Tetsuro", "last_name": "Takamatsu", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/s00418-009-0594-0" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "19365636" } }, "mesh": [ { "descriptor": "Antineoplastic Agents", "descriptor_ui": "D000970", "major_topic": false }, { "descriptor": "Camptothecin", "descriptor_ui": "D002166", "major_topic": false }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "DNA Topoisomerases, Type I", "descriptor_ui": "D004264", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Irinotecan", "descriptor_ui": "D000077146", "major_topic": false }, { "descriptor": "Microscopy, Confocal", "descriptor_ui": "D018613", "major_topic": false }, { "descriptor": "Spectrum Analysis, Raman", "descriptor_ui": "D013059", "major_topic": false }, { "descriptor": "Topoisomerase I Inhibitors", "descriptor_ui": "D059004", "major_topic": false } ], "publication": { "conference_name": null, "date": "2009 Jul", "date_precision": "unknown", "issue": "1", "normalized_date": null, "pages": "39-46", "proceedings_title": null, "publisher": "", "title": "Histochemistry and cell biology", "volume": "132", "year": 2009 }, "ssbd": { "database": [], "repository": [] }, "title": "Intracellular dynamics of topoisomerase I inhibitor, CPT-11, by slit-scanning confocal Raman microscopy.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Early detection and treatment of lung cancer is one of the most effective means of reducing cancer mortality, and to this end, chest X-ray radiography has been widely used as a screening method. A related technique based on the development of computer analysis and a flat panel detector (FPD) has enabled the functional evaluation of respiratory kinetics in the chest and is expected to be introduced into clinical practice in the near future. In this study, we developed a computer analysis algorithm to detect lung nodules and to evaluate quantitative kinetics. Breathing chest radiographs obtained by modified FPD and breath synchronization utilizing diaphragmatic analysis of vector movement were converted into four static images by sequential temporal subtraction processing, morphological enhancement processing, kinetic visualization processing, and lung region detection processing. An artificial neural network analyzed these density patterns to detect the true nodules and draw their kinetic tracks. Both the algorithm performance and the evaluation of clinical effectiveness of seven normal patients and simulated nodules showed sufficient detecting capability and kinetic imaging function without significant differences. Our technique can quantitatively evaluate the kinetic range of nodules and is effective in detecting a nodule on a breathing chest radiograph. Moreover, the application of this technique is expected to extend computer-aided diagnosis systems and facilitate the development of an automatic planning system for radiation therapy.", "classifications": [ { "id": "Tsuchiya", "label": "Group Tsuchiya", "parent": "Tsuchiya", "type": "group" }, { "id": "Tsuchiya", "label": "Team Tsuchiya", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yuichiro", "last_name": "Tsuchiya", "name": null }, { "creator_type": "author", "first_name": "Yoshie", "last_name": "Kodera", "name": null }, { "creator_type": "author", "first_name": "Rie", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Shigeru", "last_name": "Sanada", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/s10278-008-9116-1" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "18415648" } }, "mesh": [ { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Algorithms", "descriptor_ui": "D000465", "major_topic": false }, { "descriptor": "Artifacts", "descriptor_ui": "D016477", "major_topic": false }, { "descriptor": "Computer Simulation", "descriptor_ui": "D003198", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Image Processing, Computer-Assisted", "descriptor_ui": "D007091", "major_topic": false }, { "descriptor": "Kinetics", "descriptor_ui": "D007700", "major_topic": false }, { "descriptor": "Lung", "descriptor_ui": "D008168", "major_topic": false }, { "descriptor": "Lung Neoplasms", "descriptor_ui": "D008175", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Radiographic Image Interpretation, Computer-Assisted", "descriptor_ui": "D011857", "major_topic": false }, { "descriptor": "Radiography, Dual-Energy Scanned Projection", "descriptor_ui": "D015900", "major_topic": false }, { "descriptor": "Respiratory Mechanics", "descriptor_ui": "D015656", "major_topic": false }, { "descriptor": "Young Adult", "descriptor_ui": "D055815", "major_topic": false } ], "publication": { "conference_name": null, "date": "2009 Apr", "date_precision": "unknown", "issue": "2", "normalized_date": null, "pages": "126-135", "proceedings_title": null, "publisher": "", "title": "Journal of Digital Imaging: the official journal of the Society for Computer Applications in Radiology", "volume": "22", "year": 2009 }, "ssbd": { "database": [], "repository": [] }, "title": "Quantitative Kinetic Analysis of Lung Nodules Using the Temporal Subtraction Technique in Dynamic Chest Radiographies Performed with a Flat Panel Detector.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "In the developing nervous system, differentiating neurons express Delta and activate Notch signaling in their neighboring cells. As a result of Notch activation, neuronal differentiation is inhibited in neighboring cells and they remain neural progenitor cells. Thus, differentiation of neurons and maintenance of neural progenitor cells are well balanced owing to Notch signaling. Recent studies revealed that Notch signaling is under the control of more complex and dynamic regulation than previously thought, such as cell cycle dependent activation and oscillating gene expression. We discuss here recent advances in understanding how Notch signaling is regulated in the developing nervous system and what outcome each type of regulation of Notch signaling leads to. We highlight the role of Notch signaling in proliferation and differentiation of neural progenitor cells.", "classifications": [ { "id": "Imayoshi", "label": "Group Imayoshi", "parent": "Imayoshi", "type": "group" }, { "id": "Imayoshi", "label": "Team Imayoshi", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Ryoichiro", "last_name": "Kageyama", "name": null }, { "creator_type": "author", "first_name": "Toshiyuki", "last_name": "Ohtsuka", "name": null }, { "creator_type": "author", "first_name": "Hiromi", "last_name": "Shimojo", "name": null }, { "creator_type": "author", "first_name": "Itaru", "last_name": "Imayoshi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.ceb.2009.08.009" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "19783418" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Models, Biological", "descriptor_ui": "D008954", "major_topic": false }, { "descriptor": "Nervous System", "descriptor_ui": "D009420", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Receptors, Notch", "descriptor_ui": "D051880", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": true }, { "descriptor": "Stem Cells", "descriptor_ui": "D013234", "major_topic": false } ], "publication": { "conference_name": null, "date": "2009 Dec", "date_precision": "unknown", "issue": "6", "normalized_date": null, "pages": "733-740", "proceedings_title": null, "publisher": "", "title": "Current opinion in cell biology", "volume": "21", "year": 2009 }, "ssbd": { "database": [], "repository": [] }, "title": "Dynamic regulation of Notch signaling in neural progenitor cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "There is currently no effective method for preventing ATP and 2,3-bisphosphoglycerate (2,3-BPG) depletion during long-term erythrocyte storage in the cold, although these metabolites are strongly associated with cell viability and oxygen delivery after transfusion. Metabolite reduction is caused by whole metabolic networks in the cell, which are regulated by various physical or chemical factors. Mathematical modeling is a powerful tool for integrating such complex and dynamic systems. Here, we developed a mathematical model to predict metabolism in erythrocytes preserved with a mannitol-adenine-phosphate solution (MAP) at 4 degrees C, by modifying a published model of large-scale erythrocyte metabolism. Our model successfully reproduced the reported decreases in ATP and 2,3-BPG during storage. Analysis of our model identified several enzymatic reactions and factors related to ATP and 2,3-BPG depletions, which may serve as possible targets for improving blood storage methods. We also performed metabolome analysis of laboratory-made MAP-stored erythrocytes using capillary electrophoresis time-of-flight mass spectrometry (CE-TOFMS), which provided a comprehensive view of the metabolism dynamics. Alterations in the metabolic intermediate concentrations after long storage were qualitatively predicted by the model. Finally, through further systematic analysis, we also discuss the usability of our model.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Taiko", "last_name": "Nishino", "name": null }, { "creator_type": "author", "first_name": "Ayako", "last_name": "Yachie-Kinoshita", "name": null }, { "creator_type": "author", "first_name": "Akiyoshi", "last_name": "Hirayama", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Suematsu", "name": null }, { "creator_type": "author", "first_name": "Masaru", "last_name": "Tomita", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.jbiotec.2009.08.010" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "19695295" } }, "mesh": [ { "descriptor": "2,3-Diphosphoglycerate", "descriptor_ui": "D019794", "major_topic": false }, { "descriptor": "Adenosine Triphosphate", "descriptor_ui": "D000255", "major_topic": false }, { "descriptor": "Blood Preservation", "descriptor_ui": "D001793", "major_topic": false }, { "descriptor": "Cold Temperature", "descriptor_ui": "D003080", "major_topic": false }, { "descriptor": "Computational Biology", "descriptor_ui": "D019295", "major_topic": true }, { "descriptor": "Computer Simulation", "descriptor_ui": "D003198", "major_topic": false }, { "descriptor": "Electrophoresis, Capillary", "descriptor_ui": "D019075", "major_topic": false }, { "descriptor": "Erythrocytes", "descriptor_ui": "D004912", "major_topic": false }, { "descriptor": "Glycolysis", "descriptor_ui": "D006019", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mass Spectrometry", "descriptor_ui": "D013058", "major_topic": false }, { "descriptor": "Metabolome", "descriptor_ui": "D055442", "major_topic": true }, { "descriptor": "Models, Biological", "descriptor_ui": "D008954", "major_topic": true }, { "descriptor": "Solutions", "descriptor_ui": "D012996", "major_topic": false }, { "descriptor": "Time Factors", "descriptor_ui": "D013997", "major_topic": false } ], "publication": { "conference_name": null, "date": "2009 Nov", "date_precision": "unknown", "issue": "3", "normalized_date": null, "pages": "212-223", "proceedings_title": null, "publisher": "", "title": "Journal of biotechnology", "volume": "144", "year": 2009 }, "ssbd": { "database": [], "repository": [] }, "title": "In silico modeling and metabolome analysis of long-stored erythrocytes to improve blood storage methods.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "We monitored femtosecond laser induced membrane potential changes in non-excitable cells using patchclamp analysis. Membrane potential hyperpolarization of HeLa cells was evoked by 780 nm, 80 fs laser pulses focused in the cellular cytoplasm at average powers of 30-60 mW. Simultaneous detection of intracellular Ca2+ concentration and membrane potential revealed coincident photogeneration of Ca2+ waves and membrane potential hyperpolarization. By using non-excitable cells, the cell dynamics are slow enough that we can calculate the membrane potential using the steady-state approximation for ion gradients and permeabilities, as formulated in the GHK equations. The calculations predict hyperpolarization that matches the experimental measurements and indicates that the cellular response to laser irradiation is biological, and occurs via laser triggered Ca2+ which acts on Ca2+ activated K+ channels, causing hyperpolarization. Furthermore, by irradiating the cellular plasma membrane, we observed membrane potential depolarization in combination with a drop in membrane resistance that was consistent with a transient laser-induced membrane perforation. These results entail the first quantitative analysis of location-dependent laser-induced membrane potential modification and will help to clarify cellular biological responses under exposure to high intensity ultrashort laser pulses.", "classifications": [ { "id": "Fujita", "label": "Group Fujita", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Jun", "last_name": "Ando", "name": null }, { "creator_type": "author", "first_name": "Nicholas I.", "last_name": "Smith", "name": null }, { "creator_type": "author", "first_name": "Katsumasa", "last_name": "Fujita", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Kawata", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/s00249-008-0397-6" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "19137284" } }, "mesh": [ { "descriptor": "Calcium Signaling", "descriptor_ui": "D020013", "major_topic": false }, { "descriptor": "Cell Membrane", "descriptor_ui": "D002462", "major_topic": false }, { "descriptor": "Cytoplasm", "descriptor_ui": "D003593", "major_topic": false }, { "descriptor": "Electric Impedance", "descriptor_ui": "D017097", "major_topic": false }, { "descriptor": "HeLa Cells", "descriptor_ui": "D006367", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Ion Channel Gating", "descriptor_ui": "D015640", "major_topic": false }, { "descriptor": "Lasers", "descriptor_ui": "D007834", "major_topic": true }, { "descriptor": "Membrane Potentials", "descriptor_ui": "D008564", "major_topic": false }, { "descriptor": "Patch-Clamp Techniques", "descriptor_ui": "D018408", "major_topic": false }, { "descriptor": "Potassium Channels, Calcium-Activated", "descriptor_ui": "D024681", "major_topic": false } ], "publication": { "conference_name": null, "date": "2009 Feb", "date_precision": "unknown", "issue": "2", "normalized_date": null, "pages": "255-262", "proceedings_title": null, "publisher": "", "title": "European biophysics journal : EBJ", "volume": "38", "year": 2009 }, "ssbd": { "database": [], "repository": [] }, "title": "Photogeneration of membrane potential hyperpolarization and depolarization in non-excitable cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Neurogenesis occurs throughout adulthood in the mammalian brain by coordinated proliferation and differentiation of adult neural stem cells. Newborn neurons are incorporated into the functional networks of both the olfactory bulb and the hippocampal dentate gyrus, suggesting significant roles of adult neurogenesis in brain functions. In this review, we discuss the recent findings about the integration mode of new neurons into the existing neural circuits. We further address the potential significance of adult neurogenesis in higher brain functions such as olfactory and spatial memory.", "classifications": [ { "id": "Imayoshi", "label": "Group Imayoshi", "parent": "Imayoshi", "type": "group" }, { "id": "Imayoshi", "label": "Team Imayoshi", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Itaru", "last_name": "Imayoshi", "name": null }, { "creator_type": "author", "first_name": "Masayuki", "last_name": "Sakamoto", "name": null }, { "creator_type": "author", "first_name": "Toshiyuki", "last_name": "Ohtsuka", "name": null }, { "creator_type": "author", "first_name": "Ryoichiro", "last_name": "Kageyama", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/j.1440-169x.2009.01094.x" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "19298551" } }, "mesh": [ { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Brain", "descriptor_ui": "D001921", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Memory", "descriptor_ui": "D008568", "major_topic": false }, { "descriptor": "Neurogenesis", "descriptor_ui": "D055495", "major_topic": false }, { "descriptor": "Olfactory Bulb", "descriptor_ui": "D009830", "major_topic": false }, { "descriptor": "Stem Cells", "descriptor_ui": "D013234", "major_topic": false } ], "publication": { "conference_name": null, "date": "2009 Apr", "date_precision": "unknown", "issue": "3", "normalized_date": null, "pages": "379-386", "proceedings_title": null, "publisher": "", "title": "Development, growth & differentiation", "volume": "51", "year": 2009 }, "ssbd": { "database": [], "repository": [] }, "title": "Continuous neurogenesis in the adult brain.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The stress-activated protein kinases (SAPKs), namely, p38 and JNK, are members of the mitogen-activated protein kinase family and are important determinants of cell fate when cells are exposed to environmental stresses such as UV and osmostress. SAPKs are activated by SAPK kinases (SAP2Ks), which are in turn activated by various SAP2K kinases (SAP3Ks). Because conventional methods, such as immunoblotting using phospho-specific antibodies, measure the average activity of SAP3Ks in a cell population, the intracellular dynamics of SAP3K activity are largely unknown. Here, we developed a reporter of SAP3K activity toward the MKK6 SAP2K, based on fluorescence resonance energy transfer, that can uncover the dynamic behavior of SAP3K activation in cells. Using this reporter, we demonstrated that SAP3K activation occurs either synchronously or asynchronously among a cell population and in different cellular compartments in single cells, depending on the type of stress applied. In particular, SAP3Ks are activated by epidermal growth factor and osmostress on the plasma membrane, by anisomycin and UV in the cytoplasm, and by etoposide in the nucleus. These observations revealed previously unknown heterogeneity in SAPK responses and supplied answers to the question of the cellular location in which various stresses induce stimulus-specific SAPK responses.", "classifications": [ { "id": "Takekawa", "label": "Group Takekawa", "parent": "Takekawa", "type": "group" }, { "id": "Takekawa", "label": "Team Takekawa", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Taichiro", "last_name": "Tomida", "name": null }, { "creator_type": "author", "first_name": "Mutsuhiro", "last_name": "Takekawa", "name": null }, { "creator_type": "author", "first_name": "Pauline", "last_name": "O'Grady", "name": null }, { "creator_type": "author", "first_name": "Haruo", "last_name": "Saito", "name": null } ], "identifiers": { "doi": { "normalized": "10.1128/mcb.00571-09" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "19737916" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Biosensing Techniques", "descriptor_ui": "D015374", "major_topic": true }, { "descriptor": "Cell Membrane", "descriptor_ui": "D002462", "major_topic": false }, { "descriptor": "Cell Nucleus", "descriptor_ui": "D002467", "major_topic": false }, { "descriptor": "Cell Survival", "descriptor_ui": "D002470", "major_topic": false }, { "descriptor": "Chlorocebus aethiops", "descriptor_ui": "D002522", "major_topic": false }, { "descriptor": "COS Cells", "descriptor_ui": "D019556", "major_topic": false }, { "descriptor": "Enzyme Activation", "descriptor_ui": "D004789", "major_topic": false }, { "descriptor": "Epidermal Growth Factor", "descriptor_ui": "D004815", "major_topic": false }, { "descriptor": "Etoposide", "descriptor_ui": "D005047", "major_topic": false }, { "descriptor": "Fluorescence Resonance Energy Transfer", "descriptor_ui": "D031541", "major_topic": true }, { "descriptor": "Genes, Reporter", "descriptor_ui": "D017930", "major_topic": false }, { "descriptor": "HeLa Cells", "descriptor_ui": "D006367", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "MAP Kinase Kinase Kinases", "descriptor_ui": "D020930", "major_topic": false }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": false }, { "descriptor": "Subcellular Fractions", "descriptor_ui": "D013347", "major_topic": false }, { "descriptor": "Time Factors", "descriptor_ui": "D013997", "major_topic": false }, { "descriptor": "Ultraviolet Rays", "descriptor_ui": "D014466", "major_topic": false } ], "publication": { "conference_name": null, "date": "2009 Nov", "date_precision": "unknown", "issue": "22", "normalized_date": null, "pages": "6117-6127", "proceedings_title": null, "publisher": "", "title": "Molecular and Cellular Biology", "volume": "29", "year": 2009 }, "ssbd": { "database": [], "repository": [] }, "title": "Stimulus-Specific Distinctions in Spatial and Temporal Dynamics of Stress-Activated Protein Kinase Kinase Kinases Revealed by a Fluorescence Resonance Energy Transfer Biosensor▿.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The spindle orientation is regulated by the interaction of astral microtubules with the cell cortex. We have previously shown that spindles in nonpolarized adherent cells are oriented parallel to the substratum by an actin cytoskeleton- and phosphatidylinositol 3,4,5-triphosphate [PtdIns(3,4,5)P3]-dependent mechanism. Here, we show that Cdc42, a Rho family of small GTPases, has an essential role in this mechanism of spindle orientation by regulating both the actin cytoskeleton and PtdIns(3,4,5)P3. Knockdown of Cdc42 suppresses PI(3)K activity in M phase and induces spindle misorientation. Moreover, knockdown of Cdc42 disrupts the cortical actin structures in metaphase cells. Our results show that p21-activated kinase 2 (PAK2), a target of Cdc42 and/or Rac1, plays a key role in regulating actin reorganization and spindle orientation downstream from Cdc42. Surprisingly, PAK2 regulates spindle orientation in a kinase activity-independent manner. βPix, a guanine nucleotide exchange factor for Rac1 and Cdc42, is shown to mediate this kinase-independent function of PAK2. This study thus demonstrates that spindle orientation in adherent cells is regulated by two distinct pathways downstream from Cdc42 and uncovers a novel role of the Cdc42-PAK2-βPix-actin pathway for this mechanism.", "classifications": [ { "id": "Toyoshima", "label": "Group Toyoshima", "parent": "Toyoshima", "type": "group" }, { "id": "Toyoshima", "label": "Team Toyoshima", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Masaru", "last_name": "Mitsushima", "name": null }, { "creator_type": "author", "first_name": "Fumiko", "last_name": "Toyoshima", "name": null }, { "creator_type": "author", "first_name": "Eisuke", "last_name": "Nishida", "name": null } ], "identifiers": { "doi": { "normalized": "10.1128/mcb.01713-08" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "19273597" } }, "mesh": [ { "descriptor": "Actins", "descriptor_ui": "D000199", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "cdc42 GTP-Binding Protein", "descriptor_ui": "D020764", "major_topic": false }, { "descriptor": "Cell Adhesion", "descriptor_ui": "D002448", "major_topic": false }, { "descriptor": "Cell Cycle", "descriptor_ui": "D002453", "major_topic": false }, { "descriptor": "Cell Polarity", "descriptor_ui": "D016764", "major_topic": true }, { "descriptor": "Enzyme Activation", "descriptor_ui": "D004789", "major_topic": false }, { "descriptor": "Guanine Nucleotide Exchange Factors", "descriptor_ui": "D020662", "major_topic": false }, { "descriptor": "HeLa Cells", "descriptor_ui": "D006367", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "p21-Activated Kinases", "descriptor_ui": "D054462", "major_topic": false }, { "descriptor": "Phosphatidylinositol 3-Kinases", "descriptor_ui": "D019869", "major_topic": false }, { "descriptor": "Phosphatidylinositol Phosphates", "descriptor_ui": "D018129", "major_topic": false }, { "descriptor": "rac1 GTP-Binding Protein", "descriptor_ui": "D020830", "major_topic": false }, { "descriptor": "Recombinant Fusion Proteins", "descriptor_ui": "D011993", "major_topic": false }, { "descriptor": "Rho Guanine Nucleotide Exchange Factors", "descriptor_ui": "D064067", "major_topic": false }, { "descriptor": "RNA, Small Interfering", "descriptor_ui": "D034741", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Spindle Apparatus", "descriptor_ui": "D008941", "major_topic": false } ], "publication": { "conference_name": null, "date": "2009 May", "date_precision": "unknown", "issue": "10", "normalized_date": null, "pages": "2816-2827", "proceedings_title": null, "publisher": "", "title": "Molecular and Cellular Biology", "volume": "29", "year": 2009 }, "ssbd": { "database": [], "repository": [] }, "title": "Dual Role of Cdc42 in Spindle Orientation Control of Adherent Cells▿§.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The mdm2 and mdmx oncogenes play essential yet nonredundant roles in synergistic inactivatiosn of p53. However, the biochemical mechanism by which Mdmx synergizes with Mdm2 to inhibit p53 function remains obscure. Here we demonstrate that, using nonphosphorylatable mutants of Mdmx, the cooperative inhibition of p53 by Mdmx and Mdm2 was associated with cytoplasmic localization of p53, and with an increase of the interaction of Mdmx to p53 and Mdm2 in the cytoplasm. In addition, the Mdmx mutant cooperates with Mdm2 to induce ubiquitination of p53 at C-terminal lysine residues, and the integrity of the C-terminal lysines was partly required for the cooperative inhibition. The expression of subcellular localization mutants of Mdmx revealed that subcellular localization of Mdmx dictated p53 localization, and that cytoplasmic Mdmx tethered p53 in the cytoplasm and efficiently inhibited p53 activity. RNAi-mediated inhibition of Mdmx or introduction of the nuclear localization mutant of Mdmx reduced cytoplasmic retention of p53 in neuroblastoma cells, in which cytoplasmic sequestration of p53 is involved in its inactivation. Our data indicate that cytoplasmic tethering of p53 mediated by Mdmx contributes to p53 inactivation in some types of cancer cells.", "classifications": [ { "id": "Okamoto", "label": "Group Okamoto", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Chihiro", "last_name": "Ohtsubo", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Shiokawa", "name": null }, { "creator_type": "author", "first_name": "Masami", "last_name": "Kodama", "name": null }, { "creator_type": "author", "first_name": "Christian", "last_name": "Gaiddon", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Nakagama", "name": null }, { "creator_type": "author", "first_name": "Aart G.", "last_name": "Jochemsen", "name": null }, { "creator_type": "author", "first_name": "Yoichi", "last_name": "Taya", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Okamoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/j.1349-7006.2009.01180.x" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "19432880" } }, "mesh": [ { "descriptor": "Amino Acid Sequence", "descriptor_ui": "D000595", "major_topic": false }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Cytoplasm", "descriptor_ui": "D003593", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Molecular Sequence Data", "descriptor_ui": "D008969", "major_topic": false }, { "descriptor": "Phosphorylation", "descriptor_ui": "D010766", "major_topic": false }, { "descriptor": "Proto-Oncogene Proteins c-mdm2", "descriptor_ui": "D051736", "major_topic": false }, { "descriptor": "Tumor Suppressor Protein p53", "descriptor_ui": "D016159", "major_topic": false } ], "publication": { "conference_name": null, "date": "2009 Jul", "date_precision": "unknown", "issue": "7", "normalized_date": null, "pages": "1291-1299", "proceedings_title": null, "publisher": "", "title": "Cancer science", "volume": "100", "year": 2009 }, "ssbd": { "database": [], "repository": [] }, "title": "Cytoplasmic tethering is involved in synergistic inhibition of p53 by Mdmx and Mdm2.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "STDP (spike-timing-dependent synaptic plasticity) is thought to be a synaptic learning rule that embeds spike-timing information into a specific pattern of synaptic strengths in neuronal circuits, resulting in a memory. STDP consists of bidirectional long-term changes in synaptic strengths. This process includes long-term potentiation and long-term depression, which are dependent on the timing of presynaptic and postsynaptic spikings. In this review, we focus on computational aspects of signaling mechanisms that induce and maintain STDP as a key step toward the definition of a general synaptic learning rule. In addition, we discuss the temporal and spatial aspects of STDP, and the requirement of a homeostatic mechanism of STDP in vivo.", "classifications": [ { "id": "Kuroda", "label": "Group Kuroda", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Hidetoshi", "last_name": "Urakubo", "name": null }, { "creator_type": "author", "first_name": "Minoru", "last_name": "Honda", "name": null }, { "creator_type": "author", "first_name": "Keiko", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Kuroda", "name": null } ], "identifiers": { "doi": { "normalized": "10.2976/1.3137602" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "20119481" } }, "mesh": [], "publication": { "conference_name": null, "date": "2009 Aug", "date_precision": "unknown", "issue": "4", "normalized_date": null, "pages": "240-254", "proceedings_title": null, "publisher": "", "title": "HFSP Journal", "volume": "3", "year": 2009 }, "ssbd": { "database": [], "repository": [] }, "title": "Experimental and computational aspects of signaling mechanisms of spike-timing-dependent plasticity.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "We perform time-resolved observation of living cells with gold nanoparticles using surface-enhanced Raman scattering (SERS). The position and SERS spectra of 50-nm gold nanoparticles are simultaneously observed by slit-scanning Raman microscopy with high spatial and temporal resolution. From the SERS observation, we confirm the attachment of the particles on the cell surface and the entry into the cell with the subsequent generation of SERS signals from nearby molecules. We also confirm that the strong dependence of SERS spectra on the position of the particle during the transportation of the particle through the cell. The obtained SERS spectra and its temporal fluctuation indicate that the molecular signals observable by this technique are given only from within a limited volume in close proximity to the nanoparticles. This confirms the high spatial selectivity and resolution of SERS imaging for observation of biomolecules involved in cellular events in situ.", "classifications": [ { "id": "Fujita", "label": "Group Fujita", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Katsumasa", "last_name": "Fujita", "name": null }, { "creator_type": "author", "first_name": "Sawako", "last_name": "Ishitobi", "name": null }, { "creator_type": "author", "first_name": "Keisaku", "last_name": "Hamada", "name": null }, { "creator_type": "author", "first_name": "Nicholas I.", "last_name": "Smith", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Taguchi", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Inouye", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Kawata", "name": null } ], "identifiers": { "doi": { "normalized": "10.1117/1.3119242" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "19405766" } }, "mesh": [ { "descriptor": "Algorithms", "descriptor_ui": "D000465", "major_topic": true }, { "descriptor": "Biological Transport", "descriptor_ui": "D001692", "major_topic": false }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Endocytosis", "descriptor_ui": "D004705", "major_topic": false }, { "descriptor": "Gold", "descriptor_ui": "D006046", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Macrophages", "descriptor_ui": "D008264", "major_topic": false }, { "descriptor": "Nanoparticles", "descriptor_ui": "D053758", "major_topic": false }, { "descriptor": "Surface Plasmon Resonance", "descriptor_ui": "D020349", "major_topic": false } ], "publication": { "conference_name": null, "date": "2009 Mar-Apr", "date_precision": "unknown", "issue": "2", "normalized_date": null, "pages": "024038", "proceedings_title": null, "publisher": "", "title": "Journal of biomedical optics", "volume": "14", "year": 2009 }, "ssbd": { "database": [], "repository": [] }, "title": "Time-resolved observation of surface-enhanced Raman scattering from gold nanoparticles during transport through a living cell.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Induced pluripotent stem cells (iPSCs) have been generated from somatic cells by transgenic expression of Oct4 (Pou5f1), Sox2, Klf4 and Myc. A major difficulty in the application of this technology for regenerative medicine, however, is the delivery of reprogramming factors. Whereas retroviral transduction increases the risk of tumorigenicity, transient expression methods have considerably lower reprogramming efficiencies. Here we describe an efficient piggyBac transposon-based approach to generate integration-free iPSCs. Transposons carrying 2A peptide-linked reprogramming factors induced reprogramming of mouse embryonic fibroblasts with equivalent efficiencies to retroviral transduction. We removed transposons from these primary iPSCs by re-expressing transposase. Transgene-free iPSCs could be identified by negative selection. piggyBac excised without a footprint, leaving the iPSC genome without any genetic alteration. iPSCs fulfilled all criteria of pluripotency, such as pluripotency gene expression, teratoma formation and contribution to chimeras. piggyBac transposon-based reprogramming may be used to generate therapeutically applicable iPSCs.", "classifications": [ { "id": "Yusa", "label": "Group Yusa", "parent": "Eiraku", "type": "group" }, { "id": "Eiraku", "label": "Team Eiraku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Kosuke", "last_name": "Yusa", "name": null }, { "creator_type": "author", "first_name": "Roland", "last_name": "Rad", "name": null }, { "creator_type": "author", "first_name": "Junji", "last_name": "Takeda", "name": null }, { "creator_type": "author", "first_name": "Allan", "last_name": "Bradley", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/nmeth.1323" }, "pmcid": { "normalized": "PMC2677165" }, "pmid": { "normalized": "19337237" } }, "mesh": [ { "descriptor": "Alkaline Phosphatase", "descriptor_ui": "D000469", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Dedifferentiation", "descriptor_ui": "D054337", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Chimera", "descriptor_ui": "D002678", "major_topic": false }, { "descriptor": "Chromosomal Proteins, Non-Histone", "descriptor_ui": "D002868", "major_topic": false }, { "descriptor": "DNA Transposable Elements", "descriptor_ui": "D004251", "major_topic": false }, { "descriptor": "Embryo, Mammalian", "descriptor_ui": "D004622", "major_topic": false }, { "descriptor": "Fibroblasts", "descriptor_ui": "D005347", "major_topic": false }, { "descriptor": "Gene Expression", "descriptor_ui": "D015870", "major_topic": false }, { "descriptor": "Genetic Vectors", "descriptor_ui": "D005822", "major_topic": false }, { "descriptor": "Homeodomain Proteins", "descriptor_ui": "D018398", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Kruppel-Like Factor 4", "descriptor_ui": "D000090062", "major_topic": false }, { "descriptor": "Kruppel-Like Transcription Factors", "descriptor_ui": "D051741", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Moths", "descriptor_ui": "D009036", "major_topic": false }, { "descriptor": "Nanog Homeobox Protein", "descriptor_ui": "D000071317", "major_topic": false }, { "descriptor": "Octamer Transcription Factor-3", "descriptor_ui": "D050814", "major_topic": false }, { "descriptor": "Pluripotent Stem Cells", "descriptor_ui": "D039904", "major_topic": false }, { "descriptor": "Proto-Oncogene Proteins c-myc", "descriptor_ui": "D016271", "major_topic": false }, { "descriptor": "Repressor Proteins", "descriptor_ui": "D012097", "major_topic": false }, { "descriptor": "RNA-Binding Proteins", "descriptor_ui": "D016601", "major_topic": false }, { "descriptor": "SOXB1 Transcription Factors", "descriptor_ui": "D055748", "major_topic": false }, { "descriptor": "Teratoma", "descriptor_ui": "D013724", "major_topic": false }, { "descriptor": "Transfection", "descriptor_ui": "D014162", "major_topic": false }, { "descriptor": "Transgenes", "descriptor_ui": "D019076", "major_topic": false }, { "descriptor": "Transposases", "descriptor_ui": "D019895", "major_topic": false }, { "descriptor": "Valproic Acid", "descriptor_ui": "D014635", "major_topic": false } ], "publication": { "conference_name": null, "date": "2009 May", "date_precision": "unknown", "issue": "5", "normalized_date": null, "pages": "363-369", "proceedings_title": null, "publisher": "", "title": "Nature methods", "volume": "6", "year": 2009 }, "ssbd": { "database": [], "repository": [] }, "title": "Generation of transgene-free induced pluripotent mouse stem cells by the piggyBac transposon.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Optical signals based on Raman scattering, coherent anti-Stokes Raman scattering (CARS), and harmonic generation can be used to image biological molecules in living cells without labeling. Both Raman scattering and CARS signals can be used to detect frequencies of molecular vibrations and to obtain the molecular distributions in samples. Second-harmonic optical signals can also be generated in structured arrays of noncentrosymmetric molecules and can be used to detect structured aggregates of proteins, such as, collagen, myosin and tubulin. Since labeling techniques using chemical and biological reactions may cause undesirable changes in the sample, label-free molecular imaging techniques are essential for observation of living samples.", "classifications": [ { "id": "Fujita", "label": "Group Fujita", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Katsumasa", "last_name": "Fujita", "name": null }, { "creator_type": "author", "first_name": "Nicholas Isaac", "last_name": "Smith", "name": null } ], "identifiers": { "doi": { "normalized": null }, "pmcid": { "normalized": null }, "pmid": { "normalized": "19306507" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cells", "descriptor_ui": "D002477", "major_topic": false }, { "descriptor": "Diagnostic Imaging", "descriptor_ui": "D003952", "major_topic": false }, { "descriptor": "HeLa Cells", "descriptor_ui": "D006367", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Microscopy, Confocal", "descriptor_ui": "D018613", "major_topic": false }, { "descriptor": "Spectrum Analysis, Raman", "descriptor_ui": "D013059", "major_topic": false }, { "descriptor": "Staining and Labeling", "descriptor_ui": "D013194", "major_topic": false } ], "publication": { "conference_name": null, "date": "2008 Dec 31", "date_precision": "day", "issue": "6", "normalized_date": "2008-12-31", "pages": "530-535", "proceedings_title": null, "publisher": "", "title": "Molecules and cells", "volume": "26", "year": 2008 }, "ssbd": { "database": [], "repository": [] }, "title": "Label-free molecular imaging of living cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "This study was performed to understand the anatomical substrates of hypothalamic modulation of jaw movements. After cholera toxin B subunit (CTb) injection into the parvicellular reticular formation (RFp) of the rat medulla oblongata, where many trigeminal premotor neurons have been known to exist, numerous CTb-labeled neurons were found in the posterior lateral hypothalamus (PLH) bilaterally with a clear-cut ipsilateral dominance. After ipsilateral injections of biotinylated dextran amine (BDA) into the PLH and CTb into the motor trigeminal nucleus (Vm), the prominent distribution of BDA-labeled axon terminals around CTb-labeled neurons was found in the RFp region just ventral to the nucleus of the solitary tract and medial to the spinal trigeminal nucleus ipsilateral to the injection sites. Within the neuropil of the RFp, BDA-labeled axon terminals made an asymmetrical synaptic contact predominantly with dendrites and additionally with somata of the RFp neurons, some of which were labeled with CTb. It was further revealed that these BDA-labeled axon terminals were immunoreactive for vesicular glutamate transporter 2. The present data suggest that the PLH plays an important role in the control of jaw movements by exerting its glutamatergic excitatory action upon RFp neurons presynaptic to trigeminal motoneurons.", "classifications": [ { "id": "Yokota", "label": "Group Yokota", "parent": "Enomoto", "type": "group" }, { "id": "Enomoto", "label": "Team Enomoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Kazuki", "last_name": "Notsu", "name": null }, { "creator_type": "author", "first_name": "Toshiko", "last_name": "Tsumori", "name": null }, { "creator_type": "author", "first_name": "Shigefumi", "last_name": "Yokota", "name": null }, { "creator_type": "author", "first_name": "Joji", "last_name": "Sekine", "name": null }, { "creator_type": "author", "first_name": "Yukihiko", "last_name": "Yasui", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.brainres.2008.09.076" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "18948090" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Axons", "descriptor_ui": "D001369", "major_topic": false }, { "descriptor": "Biotin", "descriptor_ui": "D001710", "major_topic": false }, { "descriptor": "Cholera Toxin", "descriptor_ui": "D002772", "major_topic": false }, { "descriptor": "Dendrites", "descriptor_ui": "D003712", "major_topic": false }, { "descriptor": "Dextrans", "descriptor_ui": "D003911", "major_topic": false }, { "descriptor": "Fluorescent Dyes", "descriptor_ui": "D005456", "major_topic": false }, { "descriptor": "Hypothalamus", "descriptor_ui": "D007031", "major_topic": false }, { "descriptor": "Immunohistochemistry", "descriptor_ui": "D007150", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Medulla Oblongata", "descriptor_ui": "D008526", "major_topic": false }, { "descriptor": "Microscopy, Electron", "descriptor_ui": "D008854", "major_topic": false }, { "descriptor": "Motor Neurons", "descriptor_ui": "D009046", "major_topic": false }, { "descriptor": "Neural Pathways", "descriptor_ui": "D009434", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Rats, Wistar", "descriptor_ui": "D017208", "major_topic": false }, { "descriptor": "Reticular Formation", "descriptor_ui": "D012154", "major_topic": false }, { "descriptor": "Trigeminal Nuclei", "descriptor_ui": "D014278", "major_topic": false }, { "descriptor": "Vesicular Glutamate Transport Protein 2", "descriptor_ui": "D050599", "major_topic": false } ], "publication": { "conference_name": null, "date": "2008 Dec 9", "date_precision": "day", "issue": "", "normalized_date": "2008-12-09", "pages": "71-81", "proceedings_title": null, "publisher": "", "title": "Brain research", "volume": "1244", "year": 2008 }, "ssbd": { "database": [], "repository": [] }, "title": "Posterior lateral hypothalamic axon terminals are in contact with trigeminal premotor neurons in the parvicellular reticular formation of the rat medulla oblongata.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Azido- and fluoro- derivatives of 8-nitroguanosine were developed, and will contribute to the exploration of protein S-guanylation by endogenous nitrated nucleosides.", "classifications": [ { "id": "Akaike", "label": "Group Akaike", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yohei", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Hirobumi", "last_name": "Taguchi", "name": null }, { "creator_type": "author", "first_name": "Shigemoto", "last_name": "Fujii", "name": null }, { "creator_type": "author", "first_name": "Tomohiro", "last_name": "Sawa", "name": null }, { "creator_type": "author", "first_name": "Eriko", "last_name": "Kida", "name": null }, { "creator_type": "author", "first_name": "Chizuko", "last_name": "Kabuto", "name": null }, { "creator_type": "author", "first_name": "Takaaki", "last_name": "Akaike", "name": null }, { "creator_type": "author", "first_name": "Hirokazu", "last_name": "Arimoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1039/b810771h" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "19030560" } }, "mesh": [ { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Cyclic GMP", "descriptor_ui": "D006152", "major_topic": false }, { "descriptor": "Cysteine", "descriptor_ui": "D003545", "major_topic": false }, { "descriptor": "Guanosine", "descriptor_ui": "D006151", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Molecular Structure", "descriptor_ui": "D015394", "major_topic": false }, { "descriptor": "Nitro Compounds", "descriptor_ui": "D009574", "major_topic": false }, { "descriptor": "Protein Processing, Post-Translational", "descriptor_ui": "D011499", "major_topic": true }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false } ], "publication": { "conference_name": null, "date": "2008 Dec 7", "date_precision": "day", "issue": "45", "normalized_date": "2008-12-07", "pages": "5984-5986", "proceedings_title": null, "publisher": "", "title": "Chemical communications (Cambridge, England)", "volume": "", "year": 2008 }, "ssbd": { "database": [], "repository": [] }, "title": "8-Nitroguanosines as chemical probes of the protein S-guanylation.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Cardiac fibrosis, characterized by excessive deposition of extracellular matrix proteins, is one of the causes of heart failure, and it contributes to the impairment of cardiac function. Fibrosis of various tissues, including the heart, is believed to be regulated by the signalling pathway of angiotensin II (Ang II) and transforming growth factor (TGF)-beta. Transgenic expression of inhibitory polypeptides of the heterotrimeric G12 family G protein (Galpha(12/13)) in cardiomyocytes suppressed pressure overload-induced fibrosis without affecting hypertrophy. The expression of fibrogenic genes (TGF-beta, connective tissue growth factor, and periostin) and Ang-converting enzyme (ACE) was suppressed by the functional inhibition of Galpha(12/13). The expression of these fibrogenic genes through Galpha(12/13) by mechanical stretch was initiated by ATP and UDP released from cardiac myocytes through pannexin hemichannels. Inhibition of G-protein-coupled P2Y6 receptors suppressed the expression of ACE, fibrogenic genes, and cardiac fibrosis. These results indicate that activation of Galpha(12/13) in cardiomyocytes by the extracellular nucleotides-stimulated P2Y(6) receptor triggers fibrosis in pressure overload-induced cardiac fibrosis, which works as an upstream mediator of the signalling pathway between Ang II and TGF-beta.", "classifications": [ { "id": "Nishida", "label": "Group Nishida", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Motohiro", "last_name": "Nishida", "name": null }, { "creator_type": "author", "first_name": "Yoji", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Aya", "last_name": "Uemura", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Narita", "name": null }, { "creator_type": "author", "first_name": "Hidetoshi", "last_name": "Tozaki-Saitoh", "name": null }, { "creator_type": "author", "first_name": "Michio", "last_name": "Nakaya", "name": null }, { "creator_type": "author", "first_name": "Tomomi", "last_name": "Ide", "name": null }, { "creator_type": "author", "first_name": "Kazuhiro", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Kazuhide", "last_name": "Inoue", "name": null }, { "creator_type": "author", "first_name": "Taku", "last_name": "Nagao", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Kurose", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/emboj.2008.237" }, "pmcid": { "normalized": "PMC2599880" }, "pmid": { "normalized": "19008857" } }, "mesh": [ { "descriptor": "Adenosine Triphosphate", "descriptor_ui": "D000255", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Blood Pressure", "descriptor_ui": "D001794", "major_topic": true }, { "descriptor": "Cell Adhesion Molecules", "descriptor_ui": "D015815", "major_topic": false }, { "descriptor": "Connective Tissue Growth Factor", "descriptor_ui": "D055513", "major_topic": false }, { "descriptor": "Fibrosis", "descriptor_ui": "D005355", "major_topic": true }, { "descriptor": "Gene Expression", "descriptor_ui": "D015870", "major_topic": false }, { "descriptor": "GTP-Binding Protein alpha Subunits, G12-G13", "descriptor_ui": "D044365", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Transgenic", "descriptor_ui": "D008822", "major_topic": false }, { "descriptor": "Myocardium", "descriptor_ui": "D009206", "major_topic": false }, { "descriptor": "Myocytes, Cardiac", "descriptor_ui": "D032383", "major_topic": false }, { "descriptor": "Peptidyl-Dipeptidase A", "descriptor_ui": "D007703", "major_topic": false }, { "descriptor": "Purinergic P2 Receptor Antagonists", "descriptor_ui": "D058919", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Receptors, Purinergic P2", "descriptor_ui": "D018048", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": true }, { "descriptor": "Transforming Growth Factor beta", "descriptor_ui": "D016212", "major_topic": false }, { "descriptor": "Uridine Diphosphate", "descriptor_ui": "D014530", "major_topic": false } ], "publication": { "conference_name": null, "date": "2008 Dec 3", "date_precision": "day", "issue": "23", "normalized_date": "2008-12-03", "pages": "3104-3115", "proceedings_title": null, "publisher": "", "title": "The EMBO journal", "volume": "27", "year": 2008 }, "ssbd": { "database": [], "repository": [] }, "title": "P2Y6 receptor-Galpha12/13 signalling in cardiomyocytes triggers pressure overload-induced cardiac fibrosis.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "OBJECTIVES: This study was designed to determine whether controlled release of basic fibroblast growth factor (bFGF) might improve human cardiosphere-derived cell (hCDC) therapy in a pig model of chronic myocardial infarction. BACKGROUND: Current cell therapies for cardiac repair are limited by loss of the transplanted cells and poor differentiation. METHODS: We conducted 2 randomized, placebo-controlled studies in immunosuppressed pigs with anterior myocardial infarctions. Four weeks after coronary reperfusion, 14 pigs were randomly assigned to receive an intramyocardial injection of placebo medium with or without bFGF-incorporating hydrogel implantation. As a second study, 26 pigs were randomized to receive controlled release of bFGF combined with or without hCDCs or bone marrow-derived mesenchymal stem cell transplantation 4 weeks after reperfusion. RESULTS: Controlled release of bFGF in ischemic myocardium significantly augmented the formation of microvascular networks to enhance myocardial perfusion and contractile function. When combined with cell transplantation, the additive effects of bFGF were confined to hCDC-injected animals, but were not observed in animals receiving human bone marrow-derived mesenchymal stem cell transplantation. This was shown by increased donor-cell engraftment and enhanced cardiomyocyte differentiation in the transplanted hearts, resulting in synergistically improved ventricular function and regional wall motion and reduced infarct size. CONCLUSIONS: Controlled delivery of bFGF modulates the post-ischemic microenvironment to enhance hCDC engraftment and differentiation. This novel strategy demonstrates significant functional improvements after myocardial infarction and may potentially represent a therapeutic approach to be studied in a clinical trial in human heart failure.", "classifications": [ { "id": "Tanaka", "label": "Group Tanaka", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Naofumi", "last_name": "Takehara", "name": null }, { "creator_type": "author", "first_name": "Yoshiaki", "last_name": "Tsutsumi", "name": null }, { "creator_type": "author", "first_name": "Kento", "last_name": "Tateishi", "name": null }, { "creator_type": "author", "first_name": "Takehiro", "last_name": "Ogata", "name": null }, { "creator_type": "author", "first_name": "Hideo", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Tomomi", "last_name": "Ueyama", "name": null }, { "creator_type": "author", "first_name": "Tomosaburo", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Tetsuro", "last_name": "Takamatsu", "name": null }, { "creator_type": "author", "first_name": "Masanori", "last_name": "Fukushima", "name": null }, { "creator_type": "author", "first_name": "Masashi", "last_name": "Komeda", "name": null }, { "creator_type": "author", "first_name": "Masaaki", "last_name": "Yamagishi", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Yaku", "name": null }, { "creator_type": "author", "first_name": "Yasuhiko", "last_name": "Tabata", "name": null }, { "creator_type": "author", "first_name": "Hiroaki", "last_name": "Matsubara", "name": null }, { "creator_type": "author", "first_name": "Hidemasa", "last_name": "Oh", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.jacc.2008.06.052" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "19038683" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Bone Marrow Cells", "descriptor_ui": "D001854", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Cell Transplantation", "descriptor_ui": "D017690", "major_topic": false }, { "descriptor": "Fibroblast Growth Factor 2", "descriptor_ui": "D016222", "major_topic": false }, { "descriptor": "Heart", "descriptor_ui": "D006321", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mesenchymal Stem Cells", "descriptor_ui": "D059630", "major_topic": false }, { "descriptor": "Models, Biological", "descriptor_ui": "D008954", "major_topic": false }, { "descriptor": "Myocardial Infarction", "descriptor_ui": "D009203", "major_topic": false }, { "descriptor": "Myocardial Reperfusion", "descriptor_ui": "D015425", "major_topic": false }, { "descriptor": "Placebos", "descriptor_ui": "D010919", "major_topic": false }, { "descriptor": "Random Allocation", "descriptor_ui": "D011897", "major_topic": false }, { "descriptor": "Reperfusion", "descriptor_ui": "D015424", "major_topic": false }, { "descriptor": "Swine", "descriptor_ui": "D013552", "major_topic": false } ], "publication": { "conference_name": null, "date": "2008 Dec 2", "date_precision": "day", "issue": "23", "normalized_date": "2008-12-02", "pages": "1858-1865", "proceedings_title": null, "publisher": "", "title": "Journal of the American College of Cardiology", "volume": "52", "year": 2008 }, "ssbd": { "database": [], "repository": [] }, "title": "Controlled delivery of basic fibroblast growth factor promotes human cardiosphere-derived cell engraftment to enhance cardiac repair for chronic myocardial infarction.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "A Pd(II) catalyst for the hydroarylation of fullerene with boronic acids is presented. Treatment of C60 with an arylboronic acid in the presence of a catalytic amount of Pd(2-PyCH=NPh)(OCOC6F5)2 in H2O/1,2-Cl2C6H4 at room temperature furnishes the hydroarylation product (Ar-C60-H) in good yield with high selectivity. This complex possesses high catalytic activity paired with bench stability in the solid state.", "classifications": [ { "id": "Nanbo", "label": "Group Nanbo", "parent": "Tsuchiya", "type": "group" }, { "id": "Tsuchiya", "label": "Team Tsuchiya", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Susumu", "last_name": "Mori", "name": null }, { "creator_type": "author", "first_name": "Masakazu", "last_name": "Nambo", "name": null }, { "creator_type": "author", "first_name": "Liang-Chen", "last_name": "Chi", "name": null }, { "creator_type": "author", "first_name": "Jean", "last_name": "Bouffard", "name": null }, { "creator_type": "author", "first_name": "Kenichiro", "last_name": "Itami", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/ol801936j" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "18800842" } }, "mesh": [], "publication": { "conference_name": null, "date": "2008 Oct 16", "date_precision": "day", "issue": "20", "normalized_date": "2008-10-16", "pages": "4609-4612", "proceedings_title": null, "publisher": "", "title": "Organic letters", "volume": "10", "year": 2008 }, "ssbd": { "database": [], "repository": [] }, "title": "A bench-stable Pd catalyst for the hydroarylation of fullerene with boronic acids.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "A CH 2 -linked alpha(2,3)sialylgalactose analogue was efficiently synthesized using an Ireland-Claisen rearrangement, which was developed recently by our group for constructing a CF 2 -sialoside. The reaction conditions of the rearrangement were optimized for alpha-stereoselective formation of the CH 2 -sialoside. On the basis of the observed temperature effects, the origin of the stereoselectivity of the Ireland-Claisen rearrangement is discussed. Moreover, reconstruction of the 2alpha-hydroxyl group on the galactose unit of the rearrangement product was achieved by means of stereoselective dihydroxylation and deoxygenation.", "classifications": [ { "id": "Sodeoka", "label": "Group Sodeoka", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Toru", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Go", "last_name": "Hirai", "name": null }, { "creator_type": "author", "first_name": "Marie", "last_name": "Kato", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Hashizume", "name": null }, { "creator_type": "author", "first_name": "Taeko", "last_name": "Miyagi", "name": null }, { "creator_type": "author", "first_name": "Mikiko", "last_name": "Sodeoka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/ol801519j" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "18763792" } }, "mesh": [ { "descriptor": "Galactose", "descriptor_ui": "D005690", "major_topic": false }, { "descriptor": "N-Acetylneuraminic Acid", "descriptor_ui": "D019158", "major_topic": false }, { "descriptor": "Stereoisomerism", "descriptor_ui": "D013237", "major_topic": false }, { "descriptor": "Substrate Specificity", "descriptor_ui": "D013379", "major_topic": false }, { "descriptor": "Temperature", "descriptor_ui": "D013696", "major_topic": false } ], "publication": { "conference_name": null, "date": "2008 Oct 2", "date_precision": "day", "issue": "19", "normalized_date": "2008-10-02", "pages": "4167-4170", "proceedings_title": null, "publisher": "", "title": "Organic letters", "volume": "10", "year": 2008 }, "ssbd": { "database": [], "repository": [] }, "title": "Synthesis of CH2-linked alpha(2,3)sialylgalactose analogue: on the stereoselectivity of the key Ireland-Claisen rearrangement.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "N-type voltage-dependent calcium channels (VDCCs) play determining roles in calcium entry at sympathetic nerve terminals and trigger the release of the neurotransmitter norepinephrine. The accessory beta3 subunit of these channels preferentially forms N-type channels with a pore-forming CaV2.2 subunit. To examine its role in sympathetic nerve regulation, we established a beta3-overexpressing transgenic (beta3-Tg) mouse line. In these mice, we analyzed cardiovascular functions such as electrocardiography, blood pressure, echocardiography, and isovolumic contraction of the left ventricle with a Langendorff apparatus. Furthermore, we compared the cardiac function with that of beta3-null and CaV2.2 (alpha1B)-null mice. The beta3-Tg mice showed increased expression of the beta3 subunit, resulting in increased amounts of CaV2.2 in supracervical ganglion (SCG) neurons. The beta3-Tg mice had increased heart rate and enhanced sensitivity to N-type channel-specific blockers in electrocardiography, blood pressure, and echocardiography. In contrast, cardiac atria of the beta3-Tg mice revealed normal contractility to isoproterenol. Furthermore, their cardiac myocytes showed normal calcium channel currents, indicating unchanged calcium influx through VDCCs. Langendorff heart perfusion analysis revealed enhanced sensitivity to electric field stimulation in the beta3-Tg mice, whereas beta3-null and Cav2.2-null showed decreased responsiveness. The plasma epinephrine and norepinephrine levels in the beta3-Tg mice were significantly increased in the basal state, indicating enhanced sympathetic tone. Electrophysiological analysis in SCG neurons of beta3-Tg mice revealed increased calcium channel currents, especially N- and L-type currents. These results identify a determining role for the beta3 subunit in the N-type channel population in SCG and a major role in sympathetic nerve regulation.", "classifications": [ { "id": "Suzuki", "label": "Group Suzuki", "parent": "Takekawa", "type": "group" }, { "id": "Takekawa", "label": "Team Takekawa", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Manabu", "last_name": "Murakami", "name": null }, { "creator_type": "author", "first_name": "Takayoshi", "last_name": "Ohba", "name": null }, { "creator_type": "author", "first_name": "Feng", "last_name": "Xu", "name": null }, { "creator_type": "author", "first_name": "Eisaku", "last_name": "Satoh", "name": null }, { "creator_type": "author", "first_name": "Ichiro", "last_name": "Miyoshi", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Yoichirou", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Eiki", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Kyoichi", "last_name": "Ono", "name": null }, { "creator_type": "author", "first_name": "Hironobu", "last_name": "Sasano", "name": null }, { "creator_type": "author", "first_name": "Noriyuki", "last_name": "Kasai", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Toshihiko", "last_name": "Iijima", "name": null } ], "identifiers": { "doi": { "normalized": "10.1074/jbc.m802319200" }, "pmcid": { "normalized": "PMC3259806" }, "pmid": { "normalized": "18628210" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Blood Pressure", "descriptor_ui": "D001794", "major_topic": false }, { "descriptor": "Calcium", "descriptor_ui": "D002118", "major_topic": false }, { "descriptor": "Calcium Channels", "descriptor_ui": "D015220", "major_topic": false }, { "descriptor": "Calcium Channels, N-Type", "descriptor_ui": "D020864", "major_topic": false }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Electric Stimulation", "descriptor_ui": "D004558", "major_topic": false }, { "descriptor": "Electrocardiography", "descriptor_ui": "D004562", "major_topic": false }, { "descriptor": "Heart Rate", "descriptor_ui": "D006339", "major_topic": true }, { "descriptor": "Ion Transport", "descriptor_ui": "D017136", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Transgenic", "descriptor_ui": "D008822", "major_topic": false }, { "descriptor": "Myocardial Contraction", "descriptor_ui": "D009200", "major_topic": true }, { "descriptor": "Myocytes, Cardiac", "descriptor_ui": "D032383", "major_topic": false }, { "descriptor": "Norepinephrine", "descriptor_ui": "D009638", "major_topic": false }, { "descriptor": "Sympathetic Nervous System", "descriptor_ui": "D013564", "major_topic": false } ], "publication": { "conference_name": null, "date": "2008 Sep 5", "date_precision": "day", "issue": "36", "normalized_date": "2008-09-05", "pages": "24554-24560", "proceedings_title": null, "publisher": "", "title": "The Journal of biological chemistry", "volume": "283", "year": 2008 }, "ssbd": { "database": [], "repository": [] }, "title": "Modified sympathetic nerve system activity with overexpression of the voltage-dependent calcium channel beta3 subunit.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "After ipsilateral injections of biotinylated dextran amine (BDA) into the ventrolateral subnucleus of the nucleus tractus solitarius (vlNTS) and Fluoro-gold (FG) into the rostral ventral respiratory group (rVRG) region or into the phrenic nucleus (PhN) region in the rat, an overlapping distribution of BDA-labeled axon terminals and FG-labeled neurons was found in the Kolliker-Fuse (KF) nucleus ipsilateral to the injection sites. Using retrograde tracing combined with immunohistochemistry for glutamic acid decarboxylase isoform 67 (GAD67), we indicated that as many as 40% of the vlNTS neurons projecting to the KF were immunoreactive for GAD67. Using a combination of anterograde and retrograde tracing techniques, and immunohistochemistry for GAD67, we further demonstrated that the vlNTS axon terminals with GAD67 immunoreactivity established close contact to the rVRG- or PhN-projecting KF neurons. The present results suggest that GABAergic vlNTS fibers may exert inhibitory influences on the rVRG- as well as PhN-projecting KF neurons and these circuits may be involved in the respiratory reflexes such as the Hering-Breuer reflex.", "classifications": [ { "id": "Yokota", "label": "Group Yokota", "parent": "Enomoto", "type": "group" }, { "id": "Enomoto", "label": "Team Enomoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Shigefumi", "last_name": "Yokota", "name": null }, { "creator_type": "author", "first_name": "Toshiko", "last_name": "Tsumori", "name": null }, { "creator_type": "author", "first_name": "Tatsuro", "last_name": "Oka", "name": null }, { "creator_type": "author", "first_name": "Sawako", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Yukihiko", "last_name": "Yasui", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.brainres.2008.06.089" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "18634761" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Axonal Transport", "descriptor_ui": "D001370", "major_topic": false }, { "descriptor": "Biotin", "descriptor_ui": "D001710", "major_topic": false }, { "descriptor": "Carrier Proteins", "descriptor_ui": "D002352", "major_topic": false }, { "descriptor": "Dextrans", "descriptor_ui": "D003911", "major_topic": false }, { "descriptor": "Fluorescent Dyes", "descriptor_ui": "D005456", "major_topic": false }, { "descriptor": "gamma-Aminobutyric Acid", "descriptor_ui": "D005680", "major_topic": false }, { "descriptor": "Glutamate Decarboxylase", "descriptor_ui": "D005968", "major_topic": false }, { "descriptor": "Immunohistochemistry", "descriptor_ui": "D007150", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Microscopy, Confocal", "descriptor_ui": "D018613", "major_topic": false }, { "descriptor": "Neural Pathways", "descriptor_ui": "D009434", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Phrenic Nerve", "descriptor_ui": "D010791", "major_topic": false }, { "descriptor": "Presynaptic Terminals", "descriptor_ui": "D017729", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Rats, Wistar", "descriptor_ui": "D017208", "major_topic": false }, { "descriptor": "Respiratory Center", "descriptor_ui": "D012125", "major_topic": false }, { "descriptor": "Solitary Nucleus", "descriptor_ui": "D017552", "major_topic": false }, { "descriptor": "Stilbamidines", "descriptor_ui": "D013266", "major_topic": false }, { "descriptor": "Synaptic Transmission", "descriptor_ui": "D009435", "major_topic": false } ], "publication": { "conference_name": null, "date": "2008 Sep 4", "date_precision": "day", "issue": "", "normalized_date": "2008-09-04", "pages": "113-126", "proceedings_title": null, "publisher": "", "title": "Brain research", "volume": "1228", "year": 2008 }, "ssbd": { "database": [], "repository": [] }, "title": "GABAergic neurons in the ventrolateral subnucleus of the nucleus tractus solitarius are in contact with Kolliker-Fuse nucleus neurons projecting to the rostral ventral respiratory group and phrenic nucleus in the rat.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "This paper describes catalytic asymmetric Mannich-type reactions of beta-ketoesters and malonates using chiral palladium complexes. Although readily enolizable, carbonyl compounds are attractive substrates, the use of such compounds as nucleophiles in Mannich-type reactions has not been extensively investigated. In the presence of chiral Pd aqua complexes (2.5 mol %), beta-ketoesters reacted with various N-Boc imines (Boc=tert-butoxycarbonyl) to afford the desired beta-aminocarbonyl compounds in good yield with high to excellent stereoselectivity (up to 96:4 d.r., 95-99 % ee in most cases). In these reactions, construction of highly crowded vicinal quaternary and tertiary carbon centers was achieved in one step. A chiral Pd enolate is considered to be the key intermediate. To elucidate the stereoselectivity observed in the reaction, possible transition-state models are discussed, taking into account steric and stereoelectronic effects. Furthermore, this catalytic system was applied to the Mannich-type reaction of malonates with N-Boc imine as well as one-pot classical aminomethylation of beta-ketoesters using benzylamine salt and formalin. The reactions proceeded smoothly, and the corresponding Mannich products were obtained in high yield with moderate to good enantioselectivity.", "classifications": [ { "id": "Sodeoka", "label": "Group Sodeoka", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yoshitaka", "last_name": "Hamashima", "name": null }, { "creator_type": "author", "first_name": "Naoki", "last_name": "Sasamoto", "name": null }, { "creator_type": "author", "first_name": "Natsuko", "last_name": "Umebayashi", "name": null }, { "creator_type": "author", "first_name": "Mikiko", "last_name": "Sodeoka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/asia.200800120" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "18666282" } }, "mesh": [], "publication": { "conference_name": null, "date": "2008 Sep 1", "date_precision": "day", "issue": "8-9", "normalized_date": "2008-09-01", "pages": "1443-1455", "proceedings_title": null, "publisher": "", "title": "Chemistry, an Asian journal", "volume": "3", "year": 2008 }, "ssbd": { "database": [], "repository": [] }, "title": "Pd(II)-Catalyzed asymmetric addition reactions of 1,3-dicarbonyl compounds: Mannich-type reactions with N-Boc imines and three-component aminomethylation.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Intracellular Ca(2+) waves (CaWs) of cardiomyocytes are spontaneous events of Ca(2+) release from the sarcoplasmic reticulum that are regarded as an important substrate for triggered arrhythmias and delayed afterdepolarizations. However, little is known regarding whether or how CaWs within the heart actually produce arrhythmogenic membrane oscillation because of the lack of data confirming direct correlation between CaWs and membrane potentials (V(m)) in the heart. On the hypothesis that CaWs evoke arrhythmogenic oscillatory depolarization when they emerge synchronously and intensively in the heart, we conducted simultaneous fluorescence recording of intracellular Ca(2+) ([Ca(2+)](i)) dynamics and V(m) of ventricular myocytes on subepicardial surfaces of Langendorff-perfused rat hearts using in situ dual-view, rapid-scanning confocal microscopy. In intact hearts loaded with fluo4/acetoxymethyl ester and RH237 under perfusion with cytochalasin D at room temperature, individual myocytes exhibited Ca(2+) transients and action potentials uniformly on ventricular excitation, whereas low-K(+)-perfused (2.4 mmol/L) hearts exhibited CaWs sporadically between Ca(2+) transients without discernible membrane depolarization. Further [Ca(2+)](i) loading of the heart, produced by rapid pacing and addition of isoproterenol, evoked triggered activity and subsequent oscillatory V(m), which are caused by burst emergence of CaWs in individual myocytes. Such arrhythmogenic membrane oscillation was abolished by ryanodine or the Na(+)-Ca(2+) exchanger inhibitor SEA0400, indicating an essential role of CaWs and resultant Na(+)-Ca(2+) exchanger-mediated depolarization in triggered activity. In summary, we demonstrate a mechanistic link between intracellular CaWs and arrhythmogenic oscillatory depolarizations in the heart. Our findings provide a cellular perspective on abnormal [Ca(2+)](i) handling in the genesis of triggered arrhythmias in the heart.", "classifications": [ { "id": "Tanaka", "label": "Group Tanaka", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Katsuji", "last_name": "Fujiwara", "name": null }, { "creator_type": "author", "first_name": "Hideo", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Hiroki", "last_name": "Mani", "name": null }, { "creator_type": "author", "first_name": "Takuo", "last_name": "Nakagami", "name": null }, { "creator_type": "author", "first_name": "Tetsuro", "last_name": "Takamatsu", "name": null } ], "identifiers": { "doi": { "normalized": "10.1161/circresaha.108.176677" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "18635824" } }, "mesh": [ { "descriptor": "Action Potentials", "descriptor_ui": "D000200", "major_topic": false }, { "descriptor": "Aniline Compounds", "descriptor_ui": "D000814", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Arrhythmias, Cardiac", "descriptor_ui": "D001145", "major_topic": false }, { "descriptor": "Calcium", "descriptor_ui": "D002118", "major_topic": false }, { "descriptor": "Calcium Signaling", "descriptor_ui": "D020013", "major_topic": false }, { "descriptor": "Cardiotonic Agents", "descriptor_ui": "D002316", "major_topic": false }, { "descriptor": "Heart", "descriptor_ui": "D006321", "major_topic": false }, { "descriptor": "In Vitro Techniques", "descriptor_ui": "D066298", "major_topic": false }, { "descriptor": "Isoproterenol", "descriptor_ui": "D007545", "major_topic": false }, { "descriptor": "Microscopy, Confocal", "descriptor_ui": "D018613", "major_topic": false }, { "descriptor": "Myocytes, Cardiac", "descriptor_ui": "D032383", "major_topic": false }, { "descriptor": "Periodicity", "descriptor_ui": "D010507", "major_topic": false }, { "descriptor": "Phenyl Ethers", "descriptor_ui": "D010647", "major_topic": false }, { "descriptor": "Potassium", "descriptor_ui": "D011188", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Rats, Wistar", "descriptor_ui": "D017208", "major_topic": false }, { "descriptor": "Sarcoplasmic Reticulum", "descriptor_ui": "D012519", "major_topic": false }, { "descriptor": "Sodium-Calcium Exchanger", "descriptor_ui": "D019831", "major_topic": false } ], "publication": { "conference_name": null, "date": "2008 Aug 29", "date_precision": "day", "issue": "5", "normalized_date": "2008-08-29", "pages": "509-518", "proceedings_title": null, "publisher": "", "title": "Circulation research", "volume": "103", "year": 2008 }, "ssbd": { "database": [], "repository": [] }, "title": "Burst emergence of intracellular Ca2+ waves evokes arrhythmogenic oscillatory depolarization via the Na+-Ca2+ exchanger: simultaneous confocal recording of membrane potential and intracellular Ca2+ in the heart.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Embryonic stem (ES) cells differentiate into neuroectodermal progenitors when cultured as floating aggregates in serum-free conditions. Here, we show that strict removal of exogenous patterning factors during early differentiation steps induces efficient generation of rostral hypothalamic-like progenitors (Rax+/Six3+/Vax1+) in mouse ES cell-derived neuroectodermal cells. The use of growth factor-free chemically defined medium is critical and even the presence of exogenous insulin, which is commonly used in cell culture, strongly inhibits the differentiation via the Akt-dependent pathway. The ES cell-derived Rax+ progenitors generate Otp+/Brn2+ neuronal precursors (characteristic of rostral–dorsal hypothalamic neurons) and subsequently magnocellular vasopressinergic neurons that efficiently release the hormone upon stimulation. Differentiation markers of rostral–ventral hypothalamic precursors and neurons are induced from ES cell-derived Rax+ progenitors by treatment with Shh. Thus, in the absence of exogenous growth factors in medium, the ES cell-derived neuroectodermal cells spontaneously differentiate into rostral (particularly rostral–dorsal) hypothalamic-like progenitors, which generate characteristic hypothalamic neuroendocrine neurons in a stepwise fashion, as observed in vivo. These findings indicate that, instead of the addition of inductive signals, minimization of exogenous patterning signaling plays a key role in rostral hypothalamic specification of neural progenitors derived from pluripotent cells.", "classifications": [ { "id": "Eiraku", "label": "Group Eiraku", "parent": "Eiraku", "type": "group" }, { "id": "Eiraku", "label": "Team Eiraku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Takafumi", "last_name": "Wataya", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Ando", "name": null }, { "creator_type": "author", "first_name": "Keiko", "last_name": "Muguruma", "name": null }, { "creator_type": "author", "first_name": "Hanako", "last_name": "Ikeda", "name": null }, { "creator_type": "author", "first_name": "Kiichi", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Mototsugu", "last_name": "Eiraku", "name": null }, { "creator_type": "author", "first_name": "Masako", "last_name": "Kawada", "name": null }, { "creator_type": "author", "first_name": "Jun", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Nobuo", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Yoshiki", "last_name": "Sasai", "name": null } ], "identifiers": { "doi": { "normalized": "10.1073/pnas.0803078105" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "18697938" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Biomarkers", "descriptor_ui": "D015415", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": true }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Culture Media, Conditioned", "descriptor_ui": "D017077", "major_topic": false }, { "descriptor": "Embryonic Stem Cells", "descriptor_ui": "D053595", "major_topic": false }, { "descriptor": "Eye Proteins", "descriptor_ui": "D005136", "major_topic": false }, { "descriptor": "Flow Cytometry", "descriptor_ui": "D005434", "major_topic": false }, { "descriptor": "Gene Expression Regulation, Developmental", "descriptor_ui": "D018507", "major_topic": false }, { "descriptor": "Homeodomain Proteins", "descriptor_ui": "D018398", "major_topic": false }, { "descriptor": "Hypothalamus", "descriptor_ui": "D007031", "major_topic": false }, { "descriptor": "Insulin", "descriptor_ui": "D007328", "major_topic": false }, { "descriptor": "Intercellular Signaling Peptides and Proteins", "descriptor_ui": "D036341", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Proto-Oncogene Proteins c-akt", "descriptor_ui": "D051057", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Transcription Factors", "descriptor_ui": "D014157", "major_topic": false } ], "publication": { "conference_name": null, "date": "2008 Aug 19", "date_precision": "day", "issue": "33", "normalized_date": "2008-08-19", "pages": "11796-11801", "proceedings_title": null, "publisher": "", "title": "Proceedings of the National Academy of Sciences of the United States of America", "volume": "105", "year": 2008 }, "ssbd": { "database": [], "repository": [] }, "title": "Minimization of exogenous signals in ES cell culture induces rostral hypothalamic differentiation.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Detailed mechanistic studies on our recently reported asymmetric addition reactions of malonates to dihydroisoquinolines (DHIQs) catalyzed by chiral Pd(II) complexes were carried out. It was found that an N,O-acetal was generated in situ by the reaction of DHIQ with (Boc)2O, and cooperative action of the Pd(II) complex as an acid-base catalyst allowed the formation of a chiral Pd enolate and a reactive iminium ion via alpha-fragmentation. The iminium ion was also accessible via oxidation with DDQ as an oxidant, and a catalytic asymmetric oxidative Mannich-type reaction was achieved with tetrahydroisoquinolines (THIQs) as starting materials. This oxidation protocol was applicable to N-acryloyl-protected THIQs, allowing the efficient synthesis of optically active tetrahydrobenzo[a]quinolizidine derivatives via intramolecular Michael reaction.", "classifications": [ { "id": "Sodeoka", "label": "Group Sodeoka", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Christian", "last_name": "Dubs", "name": null }, { "creator_type": "author", "first_name": "Yoshitaka", "last_name": "Hamashima", "name": null }, { "creator_type": "author", "first_name": "Naoki", "last_name": "Sasamoto", "name": null }, { "creator_type": "author", "first_name": "Thomas M.", "last_name": "Seidel", "name": null }, { "creator_type": "author", "first_name": "Shoko", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Hashizume", "name": null }, { "creator_type": "author", "first_name": "Mikiko", "last_name": "Sodeoka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/jo800800y" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "18578499" } }, "mesh": [ { "descriptor": "Amines", "descriptor_ui": "D000588", "major_topic": false }, { "descriptor": "Catalysis", "descriptor_ui": "D002384", "major_topic": false }, { "descriptor": "Crystallography, X-Ray", "descriptor_ui": "D018360", "major_topic": false }, { "descriptor": "Esters", "descriptor_ui": "D004952", "major_topic": false }, { "descriptor": "Imines", "descriptor_ui": "D007097", "major_topic": false }, { "descriptor": "Isoquinolines", "descriptor_ui": "D007546", "major_topic": false }, { "descriptor": "Ligands", "descriptor_ui": "D008024", "major_topic": false }, { "descriptor": "Magnetic Resonance Spectroscopy", "descriptor_ui": "D009682", "major_topic": false }, { "descriptor": "Mannich Bases", "descriptor_ui": "D008352", "major_topic": false }, { "descriptor": "Models, Molecular", "descriptor_ui": "D008958", "major_topic": false }, { "descriptor": "Molecular Structure", "descriptor_ui": "D015394", "major_topic": false }, { "descriptor": "Oxidation-Reduction", "descriptor_ui": "D010084", "major_topic": false }, { "descriptor": "Palladium", "descriptor_ui": "D010165", "major_topic": false }, { "descriptor": "Spectrophotometry, Infrared", "descriptor_ui": "D013055", "major_topic": false }, { "descriptor": "Stereoisomerism", "descriptor_ui": "D013237", "major_topic": false }, { "descriptor": "Temperature", "descriptor_ui": "D013696", "major_topic": false } ], "publication": { "conference_name": null, "date": "2008 Aug 1", "date_precision": "day", "issue": "15", "normalized_date": "2008-08-01", "pages": "5859-5871", "proceedings_title": null, "publisher": "", "title": "The Journal of organic chemistry", "volume": "73", "year": 2008 }, "ssbd": { "database": [], "repository": [] }, "title": "Mechanistic studies on the catalytic asymmetric Mannich-type reaction with dihydroisoquinolines and development of oxidative Mannich-type reactions starting from tetrahydroisoquinolines.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "AIMS: Alteration of connexin43 (Cx43)-mediated intercellular communication is known to promote susceptibility to ventricular tachyarrhythmias. However, the precise mechanism of the altered Cx43 responsible for arrhythmogenesis remains unclear. We sought to understand changes in impulse propagation of ventricular myocytes under dominant-negative (DN) inhibition of Cx43 in the development of arrhythmias. METHODS AND RESULTS: Intercellular communication was inhibited in confluent monolayers of neonatal rat cultured myocytes by an adenoviral vector-mediated gene transfer for DNCx43-fused red fluorescence protein (RFP). A high-resolution, macro-zoom fluorescence imaging system was used to visualize both the fluo4- and RFP-fluorescence intensities as measures of Ca2+ transient propagation and distribution of DNCx43 inhibition, respectively, in the myocyte monolayers. DNCx43 inhibition of the monolayers resulted in not only a significant slowing of Ca2+ transient propagation velocity, but also a preferential emergence of spiral-wave reentrant arrhythmias elicited by rapid pacing. Detailed observations on the development of spiral waves revealed that the gene-transferred myocyte monolayers exhibited regional slowing of propagation and subsequent generation of wave break, resulting in reentrant arrhythmias. Furthermore, DNCx43-RFP-transferred monolayers showed higher fluorescence intensity of RFP at the break point than at the surrounding myocardium, indicating a culprit role of DNCx43 inhibition in the genesis of spiral reentry. CONCLUSION: The present results indicate that regional heterogeneity in gap-junctional communication promotes, in addition to slowing of conduction velocity, susceptibility to reentrant tachyarrhythmias.", "classifications": [ { "id": "Tanaka", "label": "Group Tanaka", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Takuo", "last_name": "Nakagami", "name": null }, { "creator_type": "author", "first_name": "Hideo", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Ping", "last_name": "Dai", "name": null }, { "creator_type": "author", "first_name": "Shien-Fong", "last_name": "Lin", "name": null }, { "creator_type": "author", "first_name": "Takuji", "last_name": "Tanabe", "name": null }, { "creator_type": "author", "first_name": "Hiroki", "last_name": "Mani", "name": null }, { "creator_type": "author", "first_name": "Katsuji", "last_name": "Fujiwara", "name": null }, { "creator_type": "author", "first_name": "Hiroaki", "last_name": "Matsubara", "name": null }, { "creator_type": "author", "first_name": "Tetsuro", "last_name": "Takamatsu", "name": null } ], "identifiers": { "doi": { "normalized": "10.1093/cvr/cvn084" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "18378510" } }, "mesh": [ { "descriptor": "Adenoviridae", "descriptor_ui": "D000256", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Arrhythmias, Cardiac", "descriptor_ui": "D001145", "major_topic": false }, { "descriptor": "Calcium", "descriptor_ui": "D002118", "major_topic": false }, { "descriptor": "Cell Communication", "descriptor_ui": "D002450", "major_topic": false }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Connexin 43", "descriptor_ui": "D018031", "major_topic": false }, { "descriptor": "Gap Junctions", "descriptor_ui": "D017629", "major_topic": false }, { "descriptor": "Gene Transfer Techniques", "descriptor_ui": "D018014", "major_topic": false }, { "descriptor": "Genetic Vectors", "descriptor_ui": "D005822", "major_topic": false }, { "descriptor": "Myocytes, Cardiac", "descriptor_ui": "D032383", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Rats, Wistar", "descriptor_ui": "D017208", "major_topic": false }, { "descriptor": "Tachycardia, Atrioventricular Nodal Reentry", "descriptor_ui": "D013611", "major_topic": false } ], "publication": { "conference_name": null, "date": "2008 Jul 1", "date_precision": "day", "issue": "1", "normalized_date": "2008-07-01", "pages": "70-79", "proceedings_title": null, "publisher": "", "title": "Cardiovascular research", "volume": "79", "year": 2008 }, "ssbd": { "database": [], "repository": [] }, "title": "Generation of reentrant arrhythmias by dominant-negative inhibition of connexin43 in rat cultured myocyte monolayers.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Various derivatives of reveromycin A, an inhibitor of eukaryotic cell growth, and spirofungin A, focusing on the 5S hydroxyl group and C18 hemisuccinyl group, were synthesized and their inhibitory effects on both the isoleucyl-tRNA synthetase activity and the survival of osteoclasts, and activities on the morphological reversion of src(ts)-NRK cells were examined. It was found that 2,3-dihydroreveromycin A is the promising derivative of reveromycin A based on the activity and stability.", "classifications": [ { "id": "Sodeoka", "label": "Group Sodeoka", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Takeshi", "last_name": "Shimizu", "name": null }, { "creator_type": "author", "first_name": "Takeo", "last_name": "Usui", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Fujikura", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Kawatani", "name": null }, { "creator_type": "author", "first_name": "Tomoharu", "last_name": "Satoh", "name": null }, { "creator_type": "author", "first_name": "Kiyotaka", "last_name": "Machida", "name": null }, { "creator_type": "author", "first_name": "Naoki", "last_name": "Kanoh", "name": null }, { "creator_type": "author", "first_name": "Je-Tae", "last_name": "Woo", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Osada", "name": null }, { "creator_type": "author", "first_name": "Mikiko", "last_name": "Sodeoka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.bmcl.2008.05.054" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "18519164" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Anti-Bacterial Agents", "descriptor_ui": "D000900", "major_topic": false }, { "descriptor": "Cell Cycle", "descriptor_ui": "D002453", "major_topic": false }, { "descriptor": "Chemistry, Pharmaceutical", "descriptor_ui": "D002626", "major_topic": false }, { "descriptor": "Inhibitory Concentration 50", "descriptor_ui": "D020128", "major_topic": false }, { "descriptor": "Isoleucine-tRNA Ligase", "descriptor_ui": "D007533", "major_topic": false }, { "descriptor": "Kidney", "descriptor_ui": "D007668", "major_topic": false }, { "descriptor": "Microbial Sensitivity Tests", "descriptor_ui": "D008826", "major_topic": false }, { "descriptor": "Models, Chemical", "descriptor_ui": "D008956", "major_topic": false }, { "descriptor": "Osteoclasts", "descriptor_ui": "D010010", "major_topic": false }, { "descriptor": "Pyrans", "descriptor_ui": "D011714", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Spiro Compounds", "descriptor_ui": "D013141", "major_topic": false }, { "descriptor": "Streptomyces", "descriptor_ui": "D013302", "major_topic": false }, { "descriptor": "Succinates", "descriptor_ui": "D013386", "major_topic": false } ], "publication": { "conference_name": null, "date": "2008 Jul 1", "date_precision": "day", "issue": "13", "normalized_date": "2008-07-01", "pages": "3756-3760", "proceedings_title": null, "publisher": "", "title": "Bioorganic & medicinal chemistry letters", "volume": "18", "year": 2008 }, "ssbd": { "database": [], "repository": [] }, "title": "Synthesis and biological activities of reveromycin A and spirofungin A derivatives.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: To elucidate the interaction of dynamics among modules that constitute biological systems, comprehensive datasets obtained from \"omics\" technologies have been used. In recent plant metabolomics approaches, the reconstruction of metabolic correlation networks has been attempted using statistical techniques. However, the results were unsatisfactory and effective data-mining techniques that apply appropriate comprehensive datasets are needed. RESULTS: Using capillary electrophoresis mass spectrometry (CE-MS) and capillary electrophoresis diode-array detection (CE-DAD), we analyzed the dynamic changes in the level of 56 basic metabolites in plant foliage (Oryza sativa L. ssp. japonica) at hourly intervals over a 24-hr period. Unsupervised clustering of comprehensive metabolic profiles using Kohonen's self-organizing map (SOM) allowed classification of the biochemical pathways activated by the light and dark cycle. The carbon and nitrogen (C/N) metabolism in both periods was also visualized as a phenotypic linkage map that connects network modules on the basis of traditional metabolic pathways rather than pairwise correlations among metabolites. The regulatory networks of C/N assimilation/dissimilation at each time point were consistent with previous works on plant metabolism. In response to environmental stress, glutathione and spermidine fluctuated synchronously with their regulatory targets. Adenine nucleosides and nicotinamide coenzymes were regulated by phosphorylation and dephosphorylation. We also demonstrated that SOM analysis was applicable to the estimation of unidentifiable metabolites in metabolome analysis. Hierarchical clustering of a correlation coefficient matrix could help identify the bottleneck enzymes that regulate metabolic networks. CONCLUSION: Our results showed that our SOM analysis with appropriate metabolic time-courses effectively revealed the synchronous dynamics among metabolic modules and elucidated the underlying biochemical functions. The application of discrimination of unidentified metabolites and the identification of bottleneck enzymatic steps even to non-targeted comprehensive analysis promise to facilitate an understanding of large-scale interactions among components in biological systems.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Shigeru", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Masanori", "last_name": "Arita", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Takaaki", "last_name": "Nishioka", "name": null }, { "creator_type": "author", "first_name": "Masaru", "last_name": "Tomita", "name": null } ], "identifiers": { "doi": { "normalized": "10.1186/1752-0509-2-51" }, "pmcid": { "normalized": "PMC2442833" }, "pmid": { "normalized": "18564421" } }, "mesh": [ { "descriptor": "Adenine", "descriptor_ui": "D000225", "major_topic": false }, { "descriptor": "Artificial Intelligence", "descriptor_ui": "D001185", "major_topic": false }, { "descriptor": "Cell Respiration", "descriptor_ui": "D019069", "major_topic": false }, { "descriptor": "Cluster Analysis", "descriptor_ui": "D016000", "major_topic": false }, { "descriptor": "Coenzymes", "descriptor_ui": "D003067", "major_topic": false }, { "descriptor": "Electrophoresis, Capillary", "descriptor_ui": "D019075", "major_topic": false }, { "descriptor": "Gene Expression Profiling", "descriptor_ui": "D020869", "major_topic": false }, { "descriptor": "Gene Expression Regulation, Plant", "descriptor_ui": "D018506", "major_topic": false }, { "descriptor": "Glutathione", "descriptor_ui": "D005978", "major_topic": false }, { "descriptor": "Mass Spectrometry", "descriptor_ui": "D013058", "major_topic": false }, { "descriptor": "Niacinamide", "descriptor_ui": "D009536", "major_topic": false }, { "descriptor": "Nitrogen", "descriptor_ui": "D009584", "major_topic": false }, { "descriptor": "Oryza", "descriptor_ui": "D012275", "major_topic": false }, { "descriptor": "Phosphorylation", "descriptor_ui": "D010766", "major_topic": false }, { "descriptor": "Photosynthesis", "descriptor_ui": "D010788", "major_topic": false }, { "descriptor": "Plant Leaves", "descriptor_ui": "D018515", "major_topic": false }, { "descriptor": "Spermidine", "descriptor_ui": "D013095", "major_topic": false }, { "descriptor": "Systems Biology", "descriptor_ui": "D049490", "major_topic": false }, { "descriptor": "Time", "descriptor_ui": "D013995", "major_topic": false } ], "publication": { "conference_name": null, "date": "2008 Jun 18", "date_precision": "day", "issue": "", "normalized_date": "2008-06-18", "pages": "51", "proceedings_title": null, "publisher": "", "title": "BMC systems biology", "volume": "2", "year": 2008 }, "ssbd": { "database": [], "repository": [] }, "title": "Time-resolved metabolomics reveals metabolic modulation in rice foliage.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The gene regulatory network of a developmental process contains many mutually repressive interactions between two genes. They are often regulated by or regulate an additional factor, which constitute prominent network motifs, called regulated and regulating mutual loops. Our database analysis on the gene regulatory network for Drosophila melanogaster indicates that those with mutual repression are working specifically for the segmentation process. To clarify their biological roles, we mathematically study the response of the regulated mutual loop with mutual repression to input stimuli. We show that the mutual repression increases the response sensitivity without affecting the threshold input level to activate the target gene expression, as long as the network output is unique for a given input level. This high sensitivity of the motif can contribute to sharpening the spatial domain pattern without changing its position, assuring a robust developmental process. We also study transient dynamics that shows shift of domain boundary, agreeing with experimental observations. Importance of mutual repression is addressed by comparing with other types of regulations.", "classifications": [ { "id": "Ishihara", "label": "Group Ishihara", "parent": "Sawai", "type": "group" }, { "id": "Sawai", "label": "Team Sawai", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Shuji", "last_name": "Ishihara", "name": null }, { "creator_type": "author", "first_name": "Tatsuo", "last_name": "Shibata", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.jtbi.2008.01.027" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "18342890" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Body Patterning", "descriptor_ui": "D019521", "major_topic": false }, { "descriptor": "Databases, Genetic", "descriptor_ui": "D030541", "major_topic": false }, { "descriptor": "Drosophila melanogaster", "descriptor_ui": "D004331", "major_topic": false }, { "descriptor": "Feedback, Physiological", "descriptor_ui": "D025461", "major_topic": false }, { "descriptor": "Gene Expression Regulation, Developmental", "descriptor_ui": "D018507", "major_topic": false }, { "descriptor": "Genes, Insect", "descriptor_ui": "D017344", "major_topic": false }, { "descriptor": "Models, Genetic", "descriptor_ui": "D008957", "major_topic": true } ], "publication": { "conference_name": null, "date": "2008 May 7", "date_precision": "day", "issue": "1", "normalized_date": "2008-05-07", "pages": "131-144", "proceedings_title": null, "publisher": "", "title": "Journal of theoretical biology", "volume": "252", "year": 2008 }, "ssbd": { "database": [], "repository": [] }, "title": "Mutual interaction in network motifs robustly sharpens gene expression in developmental processes.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Spike timing-dependent synaptic plasticity (STDP) plays an important role in neural development and information processing in the brain; however, the mechanism by which spike timing information is encoded into STDP remains unclear. Here, we show that a novel allosteric kinetics of NMDA receptors (NMDARs) is required for STDP. We developed a detailed biophysical model of STDP and found that the model required spike timing-dependent distinct suppression of NMDARs by Ca(2+)-calmodulin. This led us to predict an allosteric kinetics of NMDARs: a slow and rapid suppression of NMDARs by Ca(2+)-calmodulin with prespiking --> postspiking and postspiking --> prespiking, respectively. We found that the allosteric kinetics, but not the conventional kinetics, is consistent with specific features of amplitudes and peak time of NMDAR-mediated EPSPs in experiments. We found that the allosteric kinetics of NMDARs was also valid for synaptic plasticity induced by more complex spike trains in layer II/III of visual cortex. We extracted an essential synaptic learning rule by reduction of the allosteric STDP model and found that spike timing-dependent bidirectional role of postspiking in synaptic modification, which depends on the allosteric kinetics, is the essential principle in STDP. Thus, we propose a simple hypothesis of the allosteric kinetics of NMDARs that can coherently explain critical features of spike timing-dependent NMDAR-mediated EPSPs and synaptic plasticity.", "classifications": [ { "id": "Kuroda", "label": "Group Kuroda", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Hidetoshi", "last_name": "Urakubo", "name": null }, { "creator_type": "author", "first_name": "Minoru", "last_name": "Honda", "name": null }, { "creator_type": "author", "first_name": "Robert C.", "last_name": "Froemke", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Kuroda", "name": null } ], "identifiers": { "doi": { "normalized": "10.1523/jneurosci.0303-08.2008" }, "pmcid": { "normalized": "PMC6670607" }, "pmid": { "normalized": "18367598" } }, "mesh": [ { "descriptor": "Action Potentials", "descriptor_ui": "D000200", "major_topic": false }, { "descriptor": "Allosteric Regulation", "descriptor_ui": "D000494", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Calcium", "descriptor_ui": "D002118", "major_topic": false }, { "descriptor": "Calcium-Calmodulin-Dependent Protein Kinase Type 2", "descriptor_ui": "D054732", "major_topic": false }, { "descriptor": "Calmodulin", "descriptor_ui": "D002147", "major_topic": false }, { "descriptor": "Cyclic AMP-Dependent Protein Kinases", "descriptor_ui": "D017868", "major_topic": false }, { "descriptor": "Excitatory Amino Acid Antagonists", "descriptor_ui": "D018691", "major_topic": false }, { "descriptor": "In Vitro Techniques", "descriptor_ui": "D066298", "major_topic": false }, { "descriptor": "Models, Neurological", "descriptor_ui": "D008959", "major_topic": false }, { "descriptor": "Nerve Net", "descriptor_ui": "D009415", "major_topic": false }, { "descriptor": "Neuronal Plasticity", "descriptor_ui": "D009473", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Patch-Clamp Techniques", "descriptor_ui": "D018408", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Rats, Sprague-Dawley", "descriptor_ui": "D017207", "major_topic": false }, { "descriptor": "Receptors, N-Methyl-D-Aspartate", "descriptor_ui": "D016194", "major_topic": false }, { "descriptor": "Synapses", "descriptor_ui": "D013569", "major_topic": false }, { "descriptor": "Synaptic Transmission", "descriptor_ui": "D009435", "major_topic": false }, { "descriptor": "Time Factors", "descriptor_ui": "D013997", "major_topic": false }, { "descriptor": "Visual Cortex", "descriptor_ui": "D014793", "major_topic": false } ], "publication": { "conference_name": null, "date": "2008 Mar 26", "date_precision": "day", "issue": "13", "normalized_date": "2008-03-26", "pages": "3310-3323", "proceedings_title": null, "publisher": "", "title": "The Journal of neuroscience : the official journal of the Society for Neuroscience", "volume": "28", "year": 2008 }, "ssbd": { "database": [], "repository": [] }, "title": "Requirement of an allosteric kinetics of NMDA receptors for spike timing-dependent plasticity.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The hedgehog (Hh) signaling pathway regulates the development of many organs in mammals, and activation of this pathway is widely observed in human cancers. Although it is known that Hh signaling activates the expression of genes involved in cell growth, the precise role of the Hh pathway in cancer development is still unclear. Here, we show that constitutively activated mutants of Smoothened (Smo), a transducer of the Hh signaling pathway, inhibit the accumulation of the tumor suppressor protein p53. This inhibition was also observed in the presence of Hh ligand or with the overexpression of the transcription factors Gli1 and Gli2, downstream effectors of Smo, indicating that this inhibition is specific for the Hh pathway. We also report that Smo mutants augment p53 binding to the E3 ubiquitin-protein ligase Mdm2 and promote p53 ubiquitination. Furthermore, Hh signaling induced the phosphorylation of human Mdm2 protein on serines 166 and 186, which are activating phosphorylation sites of Mdm2. Smo mutants enhanced the proliferation of mouse embryonic fibroblasts (MEFs) while inducing a DNA-damage response. Moreover, Smo partially inhibited p53-dependent apoptosis and cell growth inhibition in oncogene-expressing MEFs. We also found that accumulation of p53 is inhibited by Hh signaling in several human cancer cell lines. Therefore, the Hh pathway may be a powerful accelerator of oncogenesis by activating cell proliferation and inhibiting the p53-mediated anti-cancer barrier induced by oncogenic stress.", "classifications": [ { "id": "Okamoto", "label": "Group Okamoto", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yoshinori", "last_name": "Abe", "name": null }, { "creator_type": "author", "first_name": "Eri", "last_name": "Oda-Sato", "name": null }, { "creator_type": "author", "first_name": "Kei", "last_name": "Tobiume", "name": null }, { "creator_type": "author", "first_name": "Keiko", "last_name": "Kawauchi", "name": null }, { "creator_type": "author", "first_name": "Yoichi", "last_name": "Taya", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Okamoto", "name": null }, { "creator_type": "author", "first_name": "Moshe", "last_name": "Oren", "name": null }, { "creator_type": "author", "first_name": "Nobuyuki", "last_name": "Tanaka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1073/pnas.0712216105" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "18359851" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Apoptosis", "descriptor_ui": "D017209", "major_topic": false }, { "descriptor": "Breast Neoplasms", "descriptor_ui": "D001943", "major_topic": false }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Cell Proliferation", "descriptor_ui": "D049109", "major_topic": false }, { "descriptor": "DNA Damage", "descriptor_ui": "D004249", "major_topic": false }, { "descriptor": "Down-Regulation", "descriptor_ui": "D015536", "major_topic": false }, { "descriptor": "Hedgehog Proteins", "descriptor_ui": "D053823", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Phosphorylation", "descriptor_ui": "D010766", "major_topic": false }, { "descriptor": "Protein Processing, Post-Translational", "descriptor_ui": "D011499", "major_topic": false }, { "descriptor": "Proto-Oncogene Proteins c-mdm2", "descriptor_ui": "D051736", "major_topic": false }, { "descriptor": "Receptors, G-Protein-Coupled", "descriptor_ui": "D043562", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": true }, { "descriptor": "Smoothened Receptor", "descriptor_ui": "D000072086", "major_topic": false }, { "descriptor": "Tumor Suppressor Protein p53", "descriptor_ui": "D016159", "major_topic": false }, { "descriptor": "Ubiquitination", "descriptor_ui": "D054875", "major_topic": false }, { "descriptor": "Veratrum Alkaloids", "descriptor_ui": "D014704", "major_topic": false } ], "publication": { "conference_name": null, "date": "2008 Mar 25", "date_precision": "day", "issue": "12", "normalized_date": "2008-03-25", "pages": "4838-4843", "proceedings_title": null, "publisher": "", "title": "Proceedings of the National Academy of Sciences of the United States of America", "volume": "105", "year": 2008 }, "ssbd": { "database": [], "repository": [] }, "title": "Hedgehog signaling overrides p53-mediated tumor suppression by activating Mdm2.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The cell-cycle transition from G1 to S phase has been difficult to visualize. We have harnessed antiphase oscillating proteins that mark cell-cycle transitions in order to develop genetically encoded fluorescent probes for this purpose. These probes effectively label individual G1 phase nuclei red and those in S/G2/M phases green. We were able to generate cultured cells and transgenic mice constitutively expressing the cell-cycle probes, in which every cell nucleus exhibits either red or green fluorescence. We performed time-lapse imaging to explore the spatiotemporal patterns of cell-cycle dynamics during the epithelial-mesenchymal transition of cultured cells, the migration and differentiation of neural progenitors in brain slices, and the development of tumors across blood vessels in live mice. These mice and cell lines will serve as model systems permitting unprecedented spatial and temporal resolution to help us better understand how the cell cycle is coordinated with various biological events.", "classifications": [ { "id": "Sawano", "label": "Group Sawano", "parent": "Shintaku", "type": "group" }, { "id": "Shintaku", "label": "Team Shintaku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Asako", "last_name": "Sakaue-Sawano", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Kurokawa", "name": null }, { "creator_type": "author", "first_name": "Toshifumi", "last_name": "Morimura", "name": null }, { "creator_type": "author", "first_name": "Aki", "last_name": "Hanyu", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Hama", "name": null }, { "creator_type": "author", "first_name": "Hatsuki", "last_name": "Osawa", "name": null }, { "creator_type": "author", "first_name": "Saori", "last_name": "Kashiwagi", "name": null }, { "creator_type": "author", "first_name": "Kiyoko", "last_name": "Fukami", "name": null }, { "creator_type": "author", "first_name": "Takaki", "last_name": "Miyata", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Miyoshi", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Imamura", "name": null }, { "creator_type": "author", "first_name": "Masaharu", "last_name": "Ogawa", "name": null }, { "creator_type": "author", "first_name": "Hisao", "last_name": "Masai", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Miyawaki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.cell.2007.12.033" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "18267078" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Cycle", "descriptor_ui": "D002453", "major_topic": true }, { "descriptor": "Cell Cycle Proteins", "descriptor_ui": "D018797", "major_topic": false }, { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Chlorocebus aethiops", "descriptor_ui": "D002522", "major_topic": false }, { "descriptor": "COS Cells", "descriptor_ui": "D019556", "major_topic": false }, { "descriptor": "Cytological Techniques", "descriptor_ui": "D003584", "major_topic": true }, { "descriptor": "Fluorescence", "descriptor_ui": "D005453", "major_topic": false }, { "descriptor": "Geminin", "descriptor_ui": "D064248", "major_topic": false }, { "descriptor": "HeLa Cells", "descriptor_ui": "D006367", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Luminescent Proteins", "descriptor_ui": "D008164", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Transgenic", "descriptor_ui": "D008822", "major_topic": false }, { "descriptor": "Microscopy, Confocal", "descriptor_ui": "D018613", "major_topic": false }, { "descriptor": "Molecular Sequence Data", "descriptor_ui": "D008969", "major_topic": false }, { "descriptor": "Morphogenesis", "descriptor_ui": "D009024", "major_topic": false }, { "descriptor": "Neoplasms", "descriptor_ui": "D009369", "major_topic": false }, { "descriptor": "Recombinant Fusion Proteins", "descriptor_ui": "D011993", "major_topic": false }, { "descriptor": "Ubiquitination", "descriptor_ui": "D054875", "major_topic": false } ], "publication": { "conference_name": null, "date": "2008 Feb 8", "date_precision": "day", "issue": "3", "normalized_date": "2008-02-08", "pages": "487-498", "proceedings_title": null, "publisher": "", "title": "Cell", "volume": "132", "year": 2008 }, "ssbd": { "database": [], "repository": [] }, "title": "Visualizing spatiotemporal dynamics of multicellular cell-cycle progression.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Epidermal growth factor receptor (EGFR) mutations have been reported as a predictive factor for favorable prognosis of gefitinib-treated patients with lung adenocarcinoma. However, its confounding with sex and smoking makes it unclear whether the EGFR mutation is independently associated with prolonged patient survival. In this study, we analyzed a large-scale database to discriminate the survival impact of EGFR mutations against those of sex and smoking after gefitinib therapy. EGFR mutations in exon19 and exon21 named drug-sensitive EGFR mutations were examined to investigate the impact of EGFR mutation, sex, and smoking status on survival of 362 gefitinib-treated patients with lung adenocarcinoma. Drug-sensitive EGFR mutations were detected in 169 patients (46.7%). The multivariate analysis including EGFR, sex, and smoking status showed that drug-sensitive EGFR mutations were significantly related to longer overall survival (OS) (P < 0.001) and progression-free survival (PFS) (P < 0.001). In addition, we investigated the impact of sex and smoking status according to EGFR mutation status, and the impact of EGFR mutation status according to sex and smoking status on survival. Sex and smoking status were not significantly associated with longer OS and PFS according to EGFR mutation status. Drug-sensitive EGFR mutations were significantly associated with longer OS and PFS according to sex or smoking status. Our results indicated that drug-sensitive EGFR mutations were the only independent factor for longer survival of patients treated with gefitinib, suggesting that patient selection based on EGFR mutation status for gefitinib therapy will lead to a better outcome for patients with lung adenocarcinoma.", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Shinichi", "last_name": "Toyooka", "name": null }, { "creator_type": "author", "first_name": "Toshimi", "last_name": "Takano", "name": null }, { "creator_type": "author", "first_name": "Takayuki", "last_name": "Kosaka", "name": null }, { "creator_type": "author", "first_name": "Katsuyuki", "last_name": "Hotta", "name": null }, { "creator_type": "author", "first_name": "Keitaro", "last_name": "Matsuo", "name": null }, { "creator_type": "author", "first_name": "Shuji", "last_name": "Ichihara", "name": null }, { "creator_type": "author", "first_name": "Yoshiro", "last_name": "Fujiwara", "name": null }, { "creator_type": "author", "first_name": "Junichi", "last_name": "Soh", "name": null }, { "creator_type": "author", "first_name": "Hiroki", "last_name": "Otani", "name": null }, { "creator_type": "author", "first_name": "Katsuyuki", "last_name": "Kiura", "name": null }, { "creator_type": "author", "first_name": "Keisuke", "last_name": "Aoe", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null }, { "creator_type": "author", "first_name": "Yuichiro", "last_name": "Ohe", "name": null }, { "creator_type": "author", "first_name": "Tetsuya", "last_name": "Mitsudomi", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Date", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/j.1349-7006.2007.00688.x" }, "pmcid": { "normalized": "PMC11158891" }, "pmid": { "normalized": "18271929" } }, "mesh": [ { "descriptor": "Adenocarcinoma", "descriptor_ui": "D000230", "major_topic": false }, { "descriptor": "Antineoplastic Agents", "descriptor_ui": "D000970", "major_topic": false }, { "descriptor": "Carcinoma, Non-Small-Cell Lung", "descriptor_ui": "D002289", "major_topic": false }, { "descriptor": "ErbB Receptors", "descriptor_ui": "D066246", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Gefitinib", "descriptor_ui": "D000077156", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Lung Neoplasms", "descriptor_ui": "D008175", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": true }, { "descriptor": "Prognosis", "descriptor_ui": "D011379", "major_topic": false }, { "descriptor": "Quinazolines", "descriptor_ui": "D011799", "major_topic": false }, { "descriptor": "Sex Factors", "descriptor_ui": "D012737", "major_topic": false }, { "descriptor": "Smoking", "descriptor_ui": "D012907", "major_topic": false }, { "descriptor": "Treatment Outcome", "descriptor_ui": "D016896", "major_topic": false } ], "publication": { "conference_name": null, "date": "2008-02", "date_precision": "month", "issue": "2", "normalized_date": "2008-02", "pages": "303-308", "proceedings_title": null, "publisher": "", "title": "Cancer Science", "volume": "99", "year": 2008 }, "ssbd": { "database": [], "repository": [] }, "title": "Epidermal growth factor receptor mutation, but not sex and smoking, is independently associated with favorable prognosis of gefitinib-treated patients with lung adenocarcinoma", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Background: Establishment and maintenance of a functional central nervous system (CNS) requires a highly orchestrated process of neural progenitor cell proliferation, cell cycle exit, and differentiation. An evolutionary conserved program consisting of Notch signalling mediated by basic Helix-Loop-Helix (bHLH) transcription factor activity is necessary for both the maintenance of neural progenitor cell character and the progression of neurogenesis; however, additional players in mammalian CNS neural specification remain largely unknown. In Drosophila we recently characterized Hamlet, a transcription factor that mediates Notch signalling and neural cell fate. Methodology/Principal Findings: Hamlet is a member of the Prdm (PRDI-BF1 and RIZ homology domain containing) proto-oncogene transcription factor family, and in this study we report that multiple genes in the Prdm family (Prdm6, 8, 12, 13 and 16) are expressed in the developing mouse CNS in a spatially and temporally restricted manner. In developing spinal cord Prdm8, 12 and 13 are expressed in precise neuronal progenitor zones suggesting that they may specify discrete neuronal subtypes. In developing telencephalon Prdm12 and 16 are expressed in the ventricular zone in a lateral to medial graded manner, and Prdm8 is expressed in a complementary domain in postmitotic neurons. In postnatal brain Prdm8 additionally shows restricted expression in cortical layers 2/3 and 4, the hippocampus, and the amygdala. To further elucidate roles of Prdm8 and 16 in the developing telencephalon we analyzed the relationship between these factors and the bHLH Hes (Hairy and enhancer of split homolog) effectors of Notch signalling. In Hes null telencephalon neural differentiation is enhanced, Prdm8 expression is upregulated, and Prdm16 expression is downregulated; conversely in utero electroporation of Hes1 into the developing telencephalon upregulates Prdm16 expression. Conclusions/Significance: Our data demonstrate that Prdm genes are regulated by the Notch-Hes pathway and represent strong candidates to control neural class specification and the sequential progression of mammalian CNS neurogenesis.", "classifications": [ { "id": "Imayoshi", "label": "Group Imayoshi", "parent": "Imayoshi", "type": "group" }, { "id": "Imayoshi", "label": "Team Imayoshi", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Emi", "last_name": "Kinameri", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Inoue", "name": null }, { "creator_type": "author", "first_name": "Jun", "last_name": "Aruga", "name": null }, { "creator_type": "author", "first_name": "Itaru", "last_name": "Imayoshi", "name": null }, { "creator_type": "author", "first_name": "Ryoichiro", "last_name": "Kageyama", "name": null }, { "creator_type": "author", "first_name": "Tomomi", "last_name": "Shimogori", "name": null }, { "creator_type": "author", "first_name": "Adrian W.", "last_name": "Moore", "name": null } ], "identifiers": { "doi": { "normalized": "10.1371/journal.pone.0003859" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "19050759" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Basic Helix-Loop-Helix Proteins", "descriptor_ui": "D051792", "major_topic": false }, { "descriptor": "Central Nervous System", "descriptor_ui": "D002490", "major_topic": false }, { "descriptor": "Embryonic Development", "descriptor_ui": "D047108", "major_topic": false }, { "descriptor": "Gene Expression", "descriptor_ui": "D015870", "major_topic": true }, { "descriptor": "Gene Expression Regulation", "descriptor_ui": "D005786", "major_topic": true }, { "descriptor": "In Situ Hybridization", "descriptor_ui": "D017403", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Multigene Family", "descriptor_ui": "D005810", "major_topic": false }, { "descriptor": "Neurogenesis", "descriptor_ui": "D055495", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Proto-Oncogenes", "descriptor_ui": "D011519", "major_topic": false }, { "descriptor": "Reverse Transcriptase Polymerase Chain Reaction", "descriptor_ui": "D020133", "major_topic": false }, { "descriptor": "Transcription Factors", "descriptor_ui": "D014157", "major_topic": false } ], "publication": { "conference_name": null, "date": "2008", "date_precision": "year", "issue": "12", "normalized_date": "2008", "pages": "", "proceedings_title": null, "publisher": "", "title": "PLoS ONE", "volume": "3", "year": 2008 }, "ssbd": { "database": [], "repository": [] }, "title": "Prdm Proto-Oncogene Transcription Factor Family Expression and Interaction with the Notch-Hes Pathway in Mouse Neurogenesis.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "", "classifications": [ { "id": "Sodeoka", "label": "Group Sodeoka", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Natsuko", "last_name": "Umebayashi", "name": null }, { "creator_type": "author", "first_name": "Yoshitaka", "last_name": "Hamashima", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Hashizume", "name": null }, { "creator_type": "author", "first_name": "Mikiko", "last_name": "Sodeoka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/anie.200705344" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "18435524" } }, "mesh": [], "publication": { "conference_name": null, "date": "2008", "date_precision": "year", "issue": "22", "normalized_date": "2008", "pages": "4196-4199", "proceedings_title": null, "publisher": "", "title": "Angewandte Chemie (International ed. in English)", "volume": "47", "year": 2008 }, "ssbd": { "database": [], "repository": [] }, "title": "Catalytic enantioselective aldol-type reaction of beta-ketosters with acetals.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "One of the major goals in evolutionary developmental biology is to understand the relationship between gene regulatory networks and the diverse morphologies and their functionalities. Are the diversities solely triggered by random events, or are they inevitable outcomes of an interplay between evolving gene networks and natural selection? Segmentation in arthropod embryogenesis represents a well-known example of body plan diversity. Striped patterns of gene expression that lead to the future body segments appear simultaneously or sequentially in long and short germ-band development, respectively. Moreover, a combination of both is found in intermediate germ-band development. Regulatory genes relevant for stripe formation are evolutionarily conserved among arthropods, therefore the differences in the observed traits are thought to have originated from how the genes are wired. To reveal the basic differences in the network structure, we have numerically evolved hundreds of gene regulatory networks that produce striped patterns of gene expression. By analyzing the topologies of the generated networks, we show that the characteristics of stripe formation in long and short germ-band development are determined by Feed-Forward Loops (FFLs) and negative Feed-Back Loops (FBLs) respectively, and those of intermediate germ-band development are determined by the interconnections between FFL and negative FBL. Network architectures, gene expression patterns and knockout responses exhibited by the artificially evolved networks agree with those reported in the fly Drosophila melanogaster and the beetle Tribolium castaneum. For other arthropod species, principal network architectures that remain largely unknown are predicted. Our results suggest that the emergence of the three modes of body segmentation in arthropods is an inherent property of the evolving networks.", "classifications": [ { "id": "Ishihara", "label": "Group Ishihara", "parent": "Sawai", "type": "group" }, { "id": "Sawai", "label": "Team Sawai", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Koichi", "last_name": "Fujimoto", "name": null }, { "creator_type": "author", "first_name": "Shuji", "last_name": "Ishihara", "name": null }, { "creator_type": "author", "first_name": "Kunihiko", "last_name": "Kaneko", "name": null } ], "identifiers": { "doi": { "normalized": "10.1371/journal.pone.0002772" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "18648662" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Body Patterning", "descriptor_ui": "D019521", "major_topic": true }, { "descriptor": "Developmental Biology", "descriptor_ui": "D015509", "major_topic": false }, { "descriptor": "Drosophila melanogaster", "descriptor_ui": "D004331", "major_topic": false }, { "descriptor": "Evolution, Molecular", "descriptor_ui": "D019143", "major_topic": false }, { "descriptor": "Gene Expression", "descriptor_ui": "D015870", "major_topic": false }, { "descriptor": "Gene Expression Regulation, Developmental", "descriptor_ui": "D018507", "major_topic": false }, { "descriptor": "Gene Regulatory Networks", "descriptor_ui": "D053263", "major_topic": false }, { "descriptor": "Models, Biological", "descriptor_ui": "D008954", "major_topic": false }, { "descriptor": "Models, Genetic", "descriptor_ui": "D008957", "major_topic": false }, { "descriptor": "Models, Theoretical", "descriptor_ui": "D008962", "major_topic": false }, { "descriptor": "Phenotype", "descriptor_ui": "D010641", "major_topic": false }, { "descriptor": "Systems Biology", "descriptor_ui": "D049490", "major_topic": false }, { "descriptor": "Tribolium", "descriptor_ui": "D014231", "major_topic": false } ], "publication": { "conference_name": null, "date": "2008", "date_precision": "year", "issue": "7", "normalized_date": "2008", "pages": "", "proceedings_title": null, "publisher": "", "title": "PLoS ONE", "volume": "3", "year": 2008 }, "ssbd": { "database": [], "repository": [] }, "title": "Network Evolution of Body Plans.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "When confronted with environmental stress, cells either activate defence mechanisms to survive, or initiate apoptosis, depending on the type of stress. Certain types of stress, such as hypoxia, heatshock and arsenite (type 1 stress), induce cells to assemble cytoplasmic stress granules (SGs), a major adaptive defence mechanism. SGs are multimolecular aggregates of stalled translation pre-initiation complexes that prevent the accumulation of mis-folded proteins. Type 2 stress, which includes X-rays and genotoxic drugs, induce apoptosis through the stress-activated p38 and JNK MAPK (SAPK) pathways. A functional relationship between the SG and SAPK responses is unknown. Here, we report that SG formation negatively regulates the SAPK apoptotic response, and that the signalling scaffold protein RACK1 functions as a mediator between the two responses. RACK1 binds to the stress-responsive MTK1 MAPKKK and facilitates its activation by type 2 stress; however, under conditions of type 1 stress, RACK1 is sequestered into SGs. Thus, type 1 conditions suppress activation of the MTK1-SAPK pathway and apoptosis induced by type 2 stress. These findings may be relevant to the problem of hypoxia-induced resistance to cancer chemotherapy.", "classifications": [ { "id": "Takekawa", "label": "Group Takekawa", "parent": "Takekawa", "type": "group" }, { "id": "Takekawa", "label": "Team Takekawa", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Kyoko", "last_name": "Arimoto", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Fukuda", "name": null }, { "creator_type": "author", "first_name": "Shinobu", "last_name": "Imajoh-Ohmi", "name": null }, { "creator_type": "author", "first_name": "Haruo", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Mutsuhiro", "last_name": "Takekawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/ncb1791" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "18836437" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Annexin A5", "descriptor_ui": "D017304", "major_topic": false }, { "descriptor": "Apoptosis", "descriptor_ui": "D017209", "major_topic": true }, { "descriptor": "Arsenites", "descriptor_ui": "D018053", "major_topic": false }, { "descriptor": "Carbocyanines", "descriptor_ui": "D002232", "major_topic": false }, { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "Chlorocebus aethiops", "descriptor_ui": "D002522", "major_topic": false }, { "descriptor": "COS Cells", "descriptor_ui": "D019556", "major_topic": false }, { "descriptor": "Cytoplasmic Granules", "descriptor_ui": "D003594", "major_topic": false }, { "descriptor": "Enzyme Inhibitors", "descriptor_ui": "D004791", "major_topic": false }, { "descriptor": "Fluorescent Dyes", "descriptor_ui": "D005456", "major_topic": false }, { "descriptor": "GTP-Binding Proteins", "descriptor_ui": "D019204", "major_topic": false }, { "descriptor": "HeLa Cells", "descriptor_ui": "D006367", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Indoles", "descriptor_ui": "D007211", "major_topic": false }, { "descriptor": "Kidney", "descriptor_ui": "D007668", "major_topic": false }, { "descriptor": "Mitogen-Activated Protein Kinases", "descriptor_ui": "D020928", "major_topic": false }, { "descriptor": "Models, Biological", "descriptor_ui": "D008954", "major_topic": false }, { "descriptor": "Neoplasm Proteins", "descriptor_ui": "D009363", "major_topic": false }, { "descriptor": "Oxidative Stress", "descriptor_ui": "D018384", "major_topic": true }, { "descriptor": "Receptors for Activated C Kinase", "descriptor_ui": "D000075370", "major_topic": false }, { "descriptor": "Receptors, Cell Surface", "descriptor_ui": "D011956", "major_topic": false }, { "descriptor": "Sodium Compounds", "descriptor_ui": "D017670", "major_topic": false }, { "descriptor": "Sulfhydryl Reagents", "descriptor_ui": "D013439", "major_topic": false }, { "descriptor": "Time Factors", "descriptor_ui": "D013997", "major_topic": false }, { "descriptor": "Transfection", "descriptor_ui": "D014162", "major_topic": false } ], "publication": { "conference_name": null, "date": "2008 Nov", "date_precision": "unknown", "issue": "11", "normalized_date": null, "pages": "1324-1332", "proceedings_title": null, "publisher": "", "title": "Nature cell biology", "volume": "10", "year": 2008 }, "ssbd": { "database": [], "repository": [] }, "title": "Formation of stress granules inhibits apoptosis by suppressing stress-responsive MAPK pathways.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The periaqueductal gray (PAG)-nucleus retroambiguus (NRA) pathway has been known to be involved in the control of vocalization and sexual behavior. To know how the amygdaloid complex influences the PAG-NRA pathway, here we first examined the synaptic organization between the central amygdaloid nucleus (CeA) fibers and the PAG neurons that project to the NRA by using anterograde and retrograde tract-tracing techniques in the rat. After ipsilateral injections of biotinylated dextran amine (BDA) into the CeA and cholera toxin B subunit (CTb) into the NRA, the prominent overlapping distribution of BDA-labeled axon terminals and CTb-labeled neurons was found ipsilaterally in the lateral/ventrolateral PAG, where some of the BDA-labeled terminals made symmetrical synaptic contacts with somata and dendrites of the CTb-labeled neurons. After CTb injection into the lateral/ventrolateral PAG, CTb-labeled neurons were distributed mainly in the medial division of the CeA. After BDA injection into the lateral/ventrolateral PAG, BDA-labeled fibers were distributed mainly in and around the NRA within the medulla oblongata. Using a combined retrograde tracing and in situ hybridization technique, we further demonstrated that more than half of the CeA neurons labeled with Fluoro-Gold (FG) injected into the lateral/ventrolateral PAG were positive for glutamic acid decarboxylase 67 mRNA and that the vast majority of PAG neurons labeled with FG injected into the NRA expressed vesicular glutamate transporter 2 mRNA. The present results suggest that the glutamatergic PAG-NRA pathway is under the inhibitory influence of the GABAergic CeA neurons.", "classifications": [ { "id": "Yokota", "label": "Group Yokota", "parent": "Enomoto", "type": "group" }, { "id": "Enomoto", "label": "Team Enomoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Tatsuro", "last_name": "Oka", "name": null }, { "creator_type": "author", "first_name": "Toshiko", "last_name": "Tsumori", "name": null }, { "creator_type": "author", "first_name": "Shigefumi", "last_name": "Yokota", "name": null }, { "creator_type": "author", "first_name": "Yukihiko", "last_name": "Yasui", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.neures.2008.10.004" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "18948150" } }, "mesh": [ { "descriptor": "Afferent Pathways", "descriptor_ui": "D000344", "major_topic": false }, { "descriptor": "Amygdala", "descriptor_ui": "D000679", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Biotin", "descriptor_ui": "D001710", "major_topic": false }, { "descriptor": "Cholera Toxin", "descriptor_ui": "D002772", "major_topic": false }, { "descriptor": "Dextrans", "descriptor_ui": "D003911", "major_topic": false }, { "descriptor": "Functional Laterality", "descriptor_ui": "D007839", "major_topic": false }, { "descriptor": "Glutamate Decarboxylase", "descriptor_ui": "D005968", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Medulla Oblongata", "descriptor_ui": "D008526", "major_topic": false }, { "descriptor": "Microscopy, Electron, Transmission", "descriptor_ui": "D046529", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Periaqueductal Gray", "descriptor_ui": "D010487", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Rats, Wistar", "descriptor_ui": "D017208", "major_topic": false }, { "descriptor": "Vesicular Glutamate Transport Protein 2", "descriptor_ui": "D050599", "major_topic": false } ], "publication": { "conference_name": null, "date": "2008 Dec", "date_precision": "unknown", "issue": "4", "normalized_date": null, "pages": "286-298", "proceedings_title": null, "publisher": "", "title": "Neuroscience research", "volume": "62", "year": 2008 }, "ssbd": { "database": [], "repository": [] }, "title": "Neuroanatomical and neurochemical organization of projections from the central amygdaloid nucleus to the nucleus retroambiguus via the periaqueductal gray in the rat.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The effect of ABT-737, a BH3-mimicking inhibitor for anti-apoptotic Bcl-2 and Bcl-X(L), but not Mcl-1, against Bcr-Abl-positive (Bcr-Abl(+)) leukaemic cells was examined. ABT-737 potently induced apoptosis in Bcr-Abl(+) chronic myeloid leukaemia (CML) cell lines and primary CML samples in vitro and prolonged the survival of mice xenografted with BV173 cells, a CML cell line. Higher expression of anti-apoptotic Bcl-2 proteins reduced cell killing by ABT-737 in each cell line, but there was no correlation between the sensitivities to ABT-737 and the specific expression patterns of Bcl-2 family proteins among cell lines. Thus, the cell killing effect of ABT-737 must be determined not only by the expression patterns of Bcl-2 family proteins but also by other mechanisms, such as high expression of Bcr-Abl, or a drug-efflux pump, in CML cells. ABT-737 augmented the cell killing effect of imatinib in Bcr-Abl(+) cells with diverse drug-resistance mechanisms unless leukaemic cells harboured imatinib-insensitive Abl kinase domain mutations, such as T315I. The combination of homoharringtonine that reduces Mcl-1 enhanced the killing by ABT-737 strongly in Bcr-Abl(+) cells even with T315I mutation. These results suggest that ABT-737 is a useful component of chemotherapies for CML with diverse drug-resistance mechanisms.", "classifications": [ { "id": "Tanaka", "label": "Group Tanaka", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Junya", "last_name": "Kuroda", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Kimura", "name": null }, { "creator_type": "author", "first_name": "Michael", "last_name": "Andreeff", "name": null }, { "creator_type": "author", "first_name": "Eishi", "last_name": "Ashihara", "name": null }, { "creator_type": "author", "first_name": "Yuri", "last_name": "Kamitsuji", "name": null }, { "creator_type": "author", "first_name": "Asumi", "last_name": "Yokota", "name": null }, { "creator_type": "author", "first_name": "Eri", "last_name": "Kawata", "name": null }, { "creator_type": "author", "first_name": "Miki", "last_name": "Takeuchi", "name": null }, { "creator_type": "author", "first_name": "Ruriko", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Yoshihide", "last_name": "Murotani", "name": null }, { "creator_type": "author", "first_name": "Yosuke", "last_name": "Matsumoto", "name": null }, { "creator_type": "author", "first_name": "Hideo", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Andreas", "last_name": "Strasser", "name": null }, { "creator_type": "author", "first_name": "Masafumi", "last_name": "Taniwaki", "name": null }, { "creator_type": "author", "first_name": "Taira", "last_name": "Maekawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/j.1365-2141.2007.06899.x" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "18028486" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Antineoplastic Agents", "descriptor_ui": "D000970", "major_topic": false }, { "descriptor": "Antineoplastic Agents, Phytogenic", "descriptor_ui": "D000972", "major_topic": false }, { "descriptor": "Antineoplastic Combined Chemotherapy Protocols", "descriptor_ui": "D000971", "major_topic": false }, { "descriptor": "Apoptosis", "descriptor_ui": "D017209", "major_topic": false }, { "descriptor": "Biphenyl Compounds", "descriptor_ui": "D001713", "major_topic": false }, { "descriptor": "Dose-Response Relationship, Drug", "descriptor_ui": "D004305", "major_topic": false }, { "descriptor": "Drug Evaluation, Preclinical", "descriptor_ui": "D004353", "major_topic": false }, { "descriptor": "Drug Resistance, Neoplasm", "descriptor_ui": "D019008", "major_topic": true }, { "descriptor": "Harringtonines", "descriptor_ui": "D006248", "major_topic": false }, { "descriptor": "Homoharringtonine", "descriptor_ui": "D000077863", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Leukemia, Myelogenous, Chronic, BCR-ABL Positive", "descriptor_ui": "D015464", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred NOD", "descriptor_ui": "D016688", "major_topic": false }, { "descriptor": "Mice, SCID", "descriptor_ui": "D016513", "major_topic": false }, { "descriptor": "Neoplasm Transplantation", "descriptor_ui": "D009368", "major_topic": false }, { "descriptor": "Nitrophenols", "descriptor_ui": "D009596", "major_topic": false }, { "descriptor": "Piperazines", "descriptor_ui": "D010879", "major_topic": false }, { "descriptor": "Proto-Oncogene Proteins c-bcl-2", "descriptor_ui": "D019253", "major_topic": false }, { "descriptor": "Sulfonamides", "descriptor_ui": "D013449", "major_topic": false }, { "descriptor": "Survival Analysis", "descriptor_ui": "D016019", "major_topic": false }, { "descriptor": "Transplantation, Heterologous", "descriptor_ui": "D014183", "major_topic": false }, { "descriptor": "Tumor Cells, Cultured", "descriptor_ui": "D014407", "major_topic": false } ], "publication": { "conference_name": null, "date": "2008 Jan", "date_precision": "unknown", "issue": "2", "normalized_date": null, "pages": "181-190", "proceedings_title": null, "publisher": "", "title": "British journal of haematology", "volume": "140", "year": 2008 }, "ssbd": { "database": [], "repository": [] }, "title": "ABT-737 is a useful component of combinatory chemotherapies for chronic myeloid leukaemias with diverse drug-resistance mechanisms.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "In the developing mammalian nervous system, neural progenitor cells first express the Notch effector Hes1 at variable levels and then proneural genes and Notch ligands in salt-and-pepper patterns. Recent real-time imaging analysis indicates that Hes1 expression in these cells oscillates with a period of about 2-3 h. Furthermore, the proneural gene Neurogenin-2 (Ngn2) and the Notch ligand gene Deltalike-1 (Dll1) are expressed cyclically in neural progenitor cells under the control of Hes1 oscillation but are expressed continuously in postmitotic neurons, which lose Hes1 expression. Hes1-driven Ngn2 and Dll1 oscillations seem to be advantageous for maintenance of a group of cells in an undifferentiated state by mutual activation of Notch signaling. This dynamic mode of gene expression would require a revision of the traditional view of how Notch-mediated lateral inhibition operates in the developing mammalian nervous system.", "classifications": [ { "id": "Imayoshi", "label": "Group Imayoshi", "parent": "Imayoshi", "type": "group" }, { "id": "Imayoshi", "label": "Team Imayoshi", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Ryoichiro", "last_name": "Kageyama", "name": null }, { "creator_type": "author", "first_name": "Toshiyuki", "last_name": "Ohtsuka", "name": null }, { "creator_type": "author", "first_name": "Hiromi", "last_name": "Shimojo", "name": null }, { "creator_type": "author", "first_name": "Itaru", "last_name": "Imayoshi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/nn.2208" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "18956012" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Gene Expression Regulation", "descriptor_ui": "D005786", "major_topic": false }, { "descriptor": "Models, Biological", "descriptor_ui": "D008954", "major_topic": false }, { "descriptor": "Neural Inhibition", "descriptor_ui": "D009433", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Nonlinear Dynamics", "descriptor_ui": "D017711", "major_topic": true }, { "descriptor": "Receptors, Notch", "descriptor_ui": "D051880", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Stem Cells", "descriptor_ui": "D013234", "major_topic": false } ], "publication": { "conference_name": null, "date": "2008 Nov", "date_precision": "unknown", "issue": "11", "normalized_date": null, "pages": "1247-1251", "proceedings_title": null, "publisher": "", "title": "Nature neuroscience", "volume": "11", "year": 2008 }, "ssbd": { "database": [], "repository": [] }, "title": "Dynamic Notch signaling in neural progenitor cells and a revised view of lateral inhibition.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "We demonstrate high-resolution fluorescence imaging in biological samples by saturated excitation (SAX) microscopy. In this technique, we saturate the population of fluorescence molecules at the excited state with high excitation intensity to induce strong nonlinear fluorescence responses in the center of laser focus, which contributes the improvement of the spatial resolution in three dimensions. Using SAX microscopy, we observed stained microtubules in HeLa cells with improved spatial resolution. We also measured the relation of the fluorescence and excitation intensity with several kinds of fluorescence dyes and, in the results, confirmed that SAX microscopy has the potential to observe any kind of fluorescence samples in current usage.", "classifications": [ { "id": "Fujita", "label": "Group Fujita", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Masahito", "last_name": "Yamanaka", "name": null }, { "creator_type": "author", "first_name": "Shogo", "last_name": "Kawano", "name": null }, { "creator_type": "author", "first_name": "Katsumasa", "last_name": "Fujita", "name": null }, { "creator_type": "author", "first_name": "Nicholas I.", "last_name": "Smith", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Kawata", "name": null } ], "identifiers": { "doi": { "normalized": "10.1117/1.2992595" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "19021372" } }, "mesh": [ { "descriptor": "HeLa Cells", "descriptor_ui": "D006367", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Image Enhancement", "descriptor_ui": "D007089", "major_topic": false }, { "descriptor": "Lighting", "descriptor_ui": "D008029", "major_topic": false }, { "descriptor": "Microscopy, Confocal", "descriptor_ui": "D018613", "major_topic": false }, { "descriptor": "Microscopy, Fluorescence", "descriptor_ui": "D008856", "major_topic": false }, { "descriptor": "Microtubules", "descriptor_ui": "D008870", "major_topic": false }, { "descriptor": "Refractometry", "descriptor_ui": "D012031", "major_topic": false }, { "descriptor": "Reproducibility of Results", "descriptor_ui": "D015203", "major_topic": false }, { "descriptor": "Sensitivity and Specificity", "descriptor_ui": "D012680", "major_topic": false } ], "publication": { "conference_name": null, "date": "2008 Sep-Oct", "date_precision": "unknown", "issue": "5", "normalized_date": null, "pages": "050507", "proceedings_title": null, "publisher": "", "title": "Journal of biomedical optics", "volume": "13", "year": 2008 }, "ssbd": { "database": [], "repository": [] }, "title": "Beyond the diffraction-limit biological imaging by saturated excitation microscopy.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Neurogenesis occurs continuously in the forebrain of adult mammals, but the functional importance of adult neurogenesis is still unclear. Here, using a genetic labeling method in adult mice, we found that continuous neurogenesis results in the replacement of the majority of granule neurons in the olfactory bulb and a substantial addition of granule neurons to the hippocampal dentate gyrus. Genetic ablation of newly formed neurons in adult mice led to a gradual decrease in the number of granule cells in the olfactory bulb, inhibition of increases in the granule cell number in the dentate gyrus and impairment of behaviors in contextual and spatial memory, which are known to depend on hippocampus. These results suggest that continuous neurogenesis is required for the maintenance and reorganization of the whole interneuron system in the olfactory bulb, the modulation and refinement of the existing neuronal circuits in the dentate gyrus and the normal behaviors involved in hippocampal-dependent memory.", "classifications": [ { "id": "Imayoshi", "label": "Group Imayoshi", "parent": "Imayoshi", "type": "group" }, { "id": "Imayoshi", "label": "Team Imayoshi", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Itaru", "last_name": "Imayoshi", "name": null }, { "creator_type": "author", "first_name": "Masayuki", "last_name": "Sakamoto", "name": null }, { "creator_type": "author", "first_name": "Toshiyuki", "last_name": "Ohtsuka", "name": null }, { "creator_type": "author", "first_name": "Keizo", "last_name": "Takao", "name": null }, { "creator_type": "author", "first_name": "Tsuyoshi", "last_name": "Miyakawa", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Yamaguchi", "name": null }, { "creator_type": "author", "first_name": "Kensaku", "last_name": "Mori", "name": null }, { "creator_type": "author", "first_name": "Toshio", "last_name": "Ikeda", "name": null }, { "creator_type": "author", "first_name": "Shigeyoshi", "last_name": "Itohara", "name": null }, { "creator_type": "author", "first_name": "Ryoichiro", "last_name": "Kageyama", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/nn.2185" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "18758458" } }, "mesh": [ { "descriptor": "AC133 Antigen", "descriptor_ui": "D000071916", "major_topic": false }, { "descriptor": "Adult Stem Cells", "descriptor_ui": "D053687", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Antigens, CD", "descriptor_ui": "D015703", "major_topic": false }, { "descriptor": "Behavior, Animal", "descriptor_ui": "D001522", "major_topic": false }, { "descriptor": "Bromodeoxyuridine", "descriptor_ui": "D001973", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Cell Proliferation", "descriptor_ui": "D049109", "major_topic": true }, { "descriptor": "Dentate Gyrus", "descriptor_ui": "D018891", "major_topic": false }, { "descriptor": "Discrimination Learning", "descriptor_ui": "D004193", "major_topic": false }, { "descriptor": "Enzyme Activation", "descriptor_ui": "D004789", "major_topic": false }, { "descriptor": "Glycoproteins", "descriptor_ui": "D006023", "major_topic": false }, { "descriptor": "Integrases", "descriptor_ui": "D019426", "major_topic": false }, { "descriptor": "Intermediate Filament Proteins", "descriptor_ui": "D007381", "major_topic": false }, { "descriptor": "Memory", "descriptor_ui": "D008568", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Inbred ICR", "descriptor_ui": "D008813", "major_topic": false }, { "descriptor": "Mice, Transgenic", "descriptor_ui": "D008822", "major_topic": false }, { "descriptor": "Nerve Tissue Proteins", "descriptor_ui": "D009419", "major_topic": false }, { "descriptor": "Nestin", "descriptor_ui": "D064231", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Odorants", "descriptor_ui": "D009812", "major_topic": false }, { "descriptor": "Olfactory Bulb", "descriptor_ui": "D009830", "major_topic": false }, { "descriptor": "Peptides", "descriptor_ui": "D010455", "major_topic": false }, { "descriptor": "Prosencephalon", "descriptor_ui": "D016548", "major_topic": false }, { "descriptor": "Tamoxifen", "descriptor_ui": "D013629", "major_topic": false } ], "publication": { "conference_name": null, "date": "2008 Oct", "date_precision": "unknown", "issue": "10", "normalized_date": null, "pages": "1153-1161", "proceedings_title": null, "publisher": "", "title": "Nature neuroscience", "volume": "11", "year": 2008 }, "ssbd": { "database": [], "repository": [] }, "title": "Roles of continuous neurogenesis in the structural and functional integrity of the adult forebrain.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The choroid plexus in the brain is unique because it is a non-neural secretory tissue. It secretes the cerebrospinal fluid and functions as a blood-brain barrier, but the precise mechanism of specification of this non-neural tissue has not yet been determined. Using mouse embryos and lineage-tracing analysis, we found that the prospective choroid plexus region initially gives rise to Cajal-Retzius cells, specialized neurons that guide neuronal migration. Inactivation of the bHLH repressor genes Hes1, Hes3 and Hes5 upregulated expression of the proneural gene neurogenin 2 (Ngn2) and prematurely depleted Bmp-expressing progenitor cells, leading to enhanced formation of Cajal-Retzius cells and complete loss of choroid plexus epithelial cells. Overexpression of Ngn2 had similar effects. These data indicate that Hes genes promote specification of the fate of choroid plexus epithelial cells rather than the fate of Cajal-Retzius cells by antagonizing Ngn2 in the dorsal telencephalic midline region, and thus this study has identified a novel role for bHLH genes in the process of deciding which cells will have a non-neural versus a neural fate.", "classifications": [ { "id": "Imayoshi", "label": "Group Imayoshi", "parent": "Imayoshi", "type": "group" }, { "id": "Imayoshi", "label": "Team Imayoshi", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Itaru", "last_name": "Imayoshi", "name": null }, { "creator_type": "author", "first_name": "Tomomi", "last_name": "Shimogori", "name": null }, { "creator_type": "author", "first_name": "Toshiyuki", "last_name": "Ohtsuka", "name": null }, { "creator_type": "author", "first_name": "Ryoichiro", "last_name": "Kageyama", "name": null } ], "identifiers": { "doi": { "normalized": "10.1242/dev.021535" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "18579678" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Basic Helix-Loop-Helix Proteins", "descriptor_ui": "D051792", "major_topic": false }, { "descriptor": "Bone Morphogenetic Proteins", "descriptor_ui": "D019485", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Cell Lineage", "descriptor_ui": "D019070", "major_topic": true }, { "descriptor": "Gene Expression Regulation, Developmental", "descriptor_ui": "D018507", "major_topic": true }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Telencephalon", "descriptor_ui": "D013687", "major_topic": false }, { "descriptor": "Up-Regulation", "descriptor_ui": "D015854", "major_topic": false } ], "publication": { "conference_name": null, "date": "2008 Aug", "date_precision": "unknown", "issue": "15", "normalized_date": null, "pages": "2531-2541", "proceedings_title": null, "publisher": "", "title": "Development (Cambridge, England)", "volume": "135", "year": 2008 }, "ssbd": { "database": [], "repository": [] }, "title": "Hes genes and neurogenin regulate non-neural versus neural fate specification in the dorsal telencephalic midline.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Cardiac hypertrophy is induced by various stresses such as hypertension and myocardial infarction. It is believed that hypertrophy is adaptive in the early phase but becomes maladaptive in the late phase. Cardiac hypertrophy develops heart failure when the heart is exposed persistently to the stresses. The increase in intracellular Ca(2+) ([Ca(2+)](i)) plays an important role in the development of hypertrophy. It is generally thought that the increase in [Ca(2+)](i) for hypertrophy occurs via G(q)-stimulated production of inositol-1,4,5-trisphosphate (IP(3)) and IP(3)-mediated release of Ca(2+) from intracellular store. However, several groups recently reported that canonical transient receptor potential (TRPC) channels are responsible for the increase in [Ca(2+)](i). Among them, three TRPC subtypes (TRPC3/TRPC6/TRPC7) are activated by another G(q)-mediated second messenger, diacylglycerol. Although several groups independently demonstrated that TRPC channels mediate receptor-stimulated and pressure overload-induced hypertrophy, there is discrepancy of which subtypes of TRPC channels predominantly mediate hypertrophy. However, there is consensus that TRPC-mediated Ca(2+) influx is essential for hypertrophy. As TRPC channels participate in pathological hypertrophy, but not physiological contraction and the relaxation cycle, TPRC channels are a new target for the treatment of hypertrophy.", "classifications": [ { "id": "Nishida", "label": "Group Nishida", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Motohiro", "last_name": "Nishida", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Kurose", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/s00210-008-0321-8" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "18600314" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Apoptosis", "descriptor_ui": "D017209", "major_topic": false }, { "descriptor": "Calcium", "descriptor_ui": "D002118", "major_topic": false }, { "descriptor": "Cardiomegaly", "descriptor_ui": "D006332", "major_topic": false }, { "descriptor": "Heart Failure", "descriptor_ui": "D006333", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Models, Biological", "descriptor_ui": "D008954", "major_topic": false }, { "descriptor": "Transient Receptor Potential Channels", "descriptor_ui": "D050051", "major_topic": false } ], "publication": { "conference_name": null, "date": "2008 Oct", "date_precision": "unknown", "issue": "4", "normalized_date": null, "pages": "395-406", "proceedings_title": null, "publisher": "", "title": "Naunyn-Schmiedeberg's archives of pharmacology", "volume": "378", "year": 2008 }, "ssbd": { "database": [], "repository": [] }, "title": "Roles of TRP channels in the development of cardiac hypertrophy.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Transcriptional initiation of each gene is assumed to be independently controlled in mammals. On the other hand, recent large-scale transcriptome analyses have shown that the genome is pervasively transcribed, such that the most of its DNA gives rise to RNAs. This raises the question of whether it is possible to pinpoint and activate a particular locus without perturbing numerous neighbouring transcripts. Here we show that intensive transcription at one locus frequently spills over into its physical neighbouring loci. Rapid induction of immediate-early genes (IEGs) in response to growth factor stimulations is accompanied by co-upregulation of their neighbouring genes. Profiling the primary transcripts in the nucleus with whole-genome tiling arrays delineated simultaneous activation of transcription centred on IEGs. Even in surrounding intergenic regions, transcriptional activation took place at the same time. Acetylation levels of histone H3 and H4 are elevated along with the IEG induction and neighbouring co-upregulation. Inhibition of the mitogen-activated protein kinase (MAPK) pathway or the transcription factor SRF suppresses all transcriptional upregulation. These results suggest that transcriptional activation has a ripple effect, which may be advantageous for coordinated expression.", "classifications": [ { "id": "Yamamoto", "label": "Group Yamamoto", "parent": "Toyoshima", "type": "group" }, { "id": "Toyoshima", "label": "Team Toyoshima", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Miki", "last_name": "Ebisuya", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "May", "last_name": "Nakajima", "name": null }, { "creator_type": "author", "first_name": "Eisuke", "last_name": "Nishida", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/ncb1771" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "19160492" } }, "mesh": [ { "descriptor": "Acetylation", "descriptor_ui": "D000107", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "DNA, Intergenic", "descriptor_ui": "D021901", "major_topic": false }, { "descriptor": "Gene Expression Regulation", "descriptor_ui": "D005786", "major_topic": false }, { "descriptor": "Genes, Immediate-Early", "descriptor_ui": "D017781", "major_topic": false }, { "descriptor": "Histones", "descriptor_ui": "D006657", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mitogen-Activated Protein Kinases", "descriptor_ui": "D020928", "major_topic": false }, { "descriptor": "NIH 3T3 Cells", "descriptor_ui": "D041681", "major_topic": false }, { "descriptor": "Oligonucleotide Array Sequence Analysis", "descriptor_ui": "D020411", "major_topic": false }, { "descriptor": "RNA, Messenger", "descriptor_ui": "D012333", "major_topic": false }, { "descriptor": "Saccharomyces cerevisiae", "descriptor_ui": "D012441", "major_topic": false }, { "descriptor": "Serum Response Factor", "descriptor_ui": "D026362", "major_topic": false }, { "descriptor": "Transcription, Genetic", "descriptor_ui": "D014158", "major_topic": true } ], "publication": { "conference_name": null, "date": "2008 Sep", "date_precision": "unknown", "issue": "9", "normalized_date": null, "pages": "1106-1113", "proceedings_title": null, "publisher": "", "title": "Nature cell biology", "volume": "10", "year": 2008 }, "ssbd": { "database": [], "repository": [] }, "title": "Ripples from neighbouring transcription.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Sulfite plays an important role in beer flavor stability. Although breeding of bottom-fermenting Saccharomyces strains that produce high levels of SO2 is desirable, it is complicated by the fact that undesirable H2S is produced as an intermediate in the same pathway. Here, we report the development of a high-level SO2-producing bottom-fermenting yeast strain by integrated metabolome and transcriptome analysis. This analysis revealed that O-acetylhomoserine (OAH) is the rate-limiting factor for the production of SO2 and H2S. Appropriate genetic modifications were then introduced into a prototype strain to increase metabolic fluxes from aspartate to OAH and from sulfate to SO2, resulting in high SO2 and low H2S production. Spontaneous mutants of an industrial strain that were resistant to both methionine and threonine analogs were then analyzed for similar metabolic fluxes. One promising mutant produced much higher levels of SO2 than the parent but produced parental levels of H2S.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Satoshi", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Jun", "last_name": "Imoto", "name": null }, { "creator_type": "author", "first_name": "Toshiko", "last_name": "Minato", "name": null }, { "creator_type": "author", "first_name": "Rie", "last_name": "Oouchi", "name": null }, { "creator_type": "author", "first_name": "Mao", "last_name": "Sugihara", "name": null }, { "creator_type": "author", "first_name": "Takeo", "last_name": "Imai", "name": null }, { "creator_type": "author", "first_name": "Tatsuji", "last_name": "Ishiguro", "name": null }, { "creator_type": "author", "first_name": "Satoru", "last_name": "Mizutani", "name": null }, { "creator_type": "author", "first_name": "Masaru", "last_name": "Tomita", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Yoshimoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1128/aem.01781-07" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "18310411" } }, "mesh": [ { "descriptor": "Aspartic Acid", "descriptor_ui": "D001224", "major_topic": false }, { "descriptor": "Enzymes", "descriptor_ui": "D004798", "major_topic": false }, { "descriptor": "Fermentation", "descriptor_ui": "D005285", "major_topic": false }, { "descriptor": "Food Microbiology", "descriptor_ui": "D005516", "major_topic": true }, { "descriptor": "Gene Deletion", "descriptor_ui": "D017353", "major_topic": false }, { "descriptor": "Gene Dosage", "descriptor_ui": "D018628", "major_topic": false }, { "descriptor": "Gene Expression Profiling", "descriptor_ui": "D020869", "major_topic": true }, { "descriptor": "Homoserine", "descriptor_ui": "D006714", "major_topic": false }, { "descriptor": "Hydrogen Sulfide", "descriptor_ui": "D006862", "major_topic": false }, { "descriptor": "Metabolic Networks and Pathways", "descriptor_ui": "D053858", "major_topic": false }, { "descriptor": "Mutagenesis, Insertional", "descriptor_ui": "D016254", "major_topic": false }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": false }, { "descriptor": "Saccharomyces cerevisiae", "descriptor_ui": "D012441", "major_topic": false }, { "descriptor": "Saccharomyces cerevisiae Proteins", "descriptor_ui": "D029701", "major_topic": false }, { "descriptor": "Sulfates", "descriptor_ui": "D013431", "major_topic": false }, { "descriptor": "Sulfur Dioxide", "descriptor_ui": "D013458", "major_topic": false } ], "publication": { "conference_name": null, "date": "2008 May", "date_precision": "unknown", "issue": "9", "normalized_date": null, "pages": "2787-2796", "proceedings_title": null, "publisher": "", "title": "Applied and Environmental Microbiology", "volume": "74", "year": 2008 }, "ssbd": { "database": [], "repository": [] }, "title": "Development of Bottom-Fermenting Saccharomyces Strains That Produce High SO2 Levels, Using Integrated Metabolome and Transcriptome Analysis▿.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Oseltamivir (Tamiflu) and zanamivir (Relenza), two extensively used clinically effective anti-influenza drugs, are viral sialidase (also known as neuraminidase) inhibitors that prevent the release of progeny virions and thereby limit the spread of infection. Recently mortalities and neuropsychiatric events have been reported with the use of oseltamivir, especially in pediatric cases in Japan, suggesting that these drugs might also inhibit endogenous enzymes involved in sialic acid metabolism, including sialidase, sialyltransferase, and CMP-synthase, in addition to their inhibitory effects on the viral sialidase. The possible inhibition could account for some of the rare side effects of oseltamivir. However, there has been little direct evidence in regard to the sensitivities of animal sialidases to these drugs. Here, we examined whether these inhibitors might indeed affect the activities of human sialidases, which differ in primary structures and enzyme properties but possess tertiary structures similar to those of the viral enzymes. Using recombinant enzymes corresponding to the four human sialidases identified so far, we found that oseltamivir carboxylate scarcely affected the activities of any of the sialidases, even at 1 mM, while zanamivir significantly inhibited the human sialidases NEU3 and NEU2 in the micromolar range (Ki, 3.7 ± 0.48 and 12.9 ± 0.07 μM, respectively), providing a contrast to the low nanomolar concentrations at which these drugs block the activity of the viral sialidases.", "classifications": [ { "id": "Sodeoka", "label": "Group Sodeoka", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Keiko", "last_name": "Hata", "name": null }, { "creator_type": "author", "first_name": "Koichi", "last_name": "Koseki", "name": null }, { "creator_type": "author", "first_name": "Kazunori", "last_name": "Yamaguchi", "name": null }, { "creator_type": "author", "first_name": "Setsuko", "last_name": "Moriya", "name": null }, { "creator_type": "author", "first_name": "Yasuo", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Sangchai", "last_name": "Yingsakmongkon", "name": null }, { "creator_type": "author", "first_name": "Go", "last_name": "Hirai", "name": null }, { "creator_type": "author", "first_name": "Mikiko", "last_name": "Sodeoka", "name": null }, { "creator_type": "author", "first_name": "Mark", "last_name": "von Itzstein", "name": null }, { "creator_type": "author", "first_name": "Taeko", "last_name": "Miyagi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1128/aac.00344-08" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "18694948" } }, "mesh": [ { "descriptor": "Antiviral Agents", "descriptor_ui": "D000998", "major_topic": false }, { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "Enzyme Inhibitors", "descriptor_ui": "D004791", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "In Vitro Techniques", "descriptor_ui": "D066298", "major_topic": false }, { "descriptor": "Kinetics", "descriptor_ui": "D007700", "major_topic": false }, { "descriptor": "Neuraminidase", "descriptor_ui": "D009439", "major_topic": false }, { "descriptor": "Orthomyxoviridae", "descriptor_ui": "D009975", "major_topic": false }, { "descriptor": "Oseltamivir", "descriptor_ui": "D053139", "major_topic": false }, { "descriptor": "Recombinant Proteins", "descriptor_ui": "D011994", "major_topic": false }, { "descriptor": "RNA, Messenger", "descriptor_ui": "D012333", "major_topic": false }, { "descriptor": "Zanamivir", "descriptor_ui": "D053243", "major_topic": false } ], "publication": { "conference_name": null, "date": "2008 Oct", "date_precision": "unknown", "issue": "10", "normalized_date": null, "pages": "3484-3491", "proceedings_title": null, "publisher": "", "title": "Antimicrobial Agents and Chemotherapy", "volume": "52", "year": 2008 }, "ssbd": { "database": [], "repository": [] }, "title": "Limited Inhibitory Effects of Oseltamivir and Zanamivir on Human Sialidases▿.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Epidermal growth factor receptor (EGFR) mutations play substantial roles in genesis and proliferation of non-small-cell lung cancers (NSCLCs). We recently found that reproductive factors have a substantial impact on risk of development of NSCLCs featuring such EGFR mutations. Therefore, we explored the influence of dietary habits on NSCLC risk with reference to the EGFR mutational status. We conducted a case-control study using 353 patients with NSCLCs (122 EGFR mutated and 231 EGFR wild-type) and 1765 age-sex matched non-cancer control subjects. Dietary exposure was based on a semiquantitative food frequency questionnaire and impact of major food items, like meats, seafoods, vegetables and soybean products was assessed by multivariate logistic regression. Soybean products demonstrated a protective association with EGFR mutated, but not EGFR wild-type NSCLCs, with multivariate-adjusted odds ratios and 95% confidence intervals for the 2nd and 3rd tertile of soybean product consumption of 0.79 (0.50-1.27) and 0.56 (0.34-0.93) relative to those in the lowest tertile (trend P = 0.023). In conclusion, soy consumption may exert a protective association against the development of NSCLCs with EGFR mutations, providing possible insights into mechanisms of their genesis.", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Keitaro", "last_name": "Matsuo", "name": null }, { "creator_type": "author", "first_name": "Akio", "last_name": "Hiraki", "name": null }, { "creator_type": "author", "first_name": "Hidemi", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Takayuki", "last_name": "Kosaka", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Kaoru", "last_name": "Hirose", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Wakai", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null }, { "creator_type": "author", "first_name": "Tetsuya", "last_name": "Mitsudomi", "name": null }, { "creator_type": "author", "first_name": "Kazuo", "last_name": "Tajima", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/j.1349-7006.2008.00812.x" }, "pmcid": { "normalized": "PMC11159498" }, "pmid": { "normalized": "18429954" } }, "mesh": [ { "descriptor": "Adenocarcinoma", "descriptor_ui": "D000230", "major_topic": false }, { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Carcinoma, Large Cell", "descriptor_ui": "D018287", "major_topic": false }, { "descriptor": "Carcinoma, Non-Small-Cell Lung", "descriptor_ui": "D002289", "major_topic": false }, { "descriptor": "Carcinoma, Squamous Cell", "descriptor_ui": "D002294", "major_topic": false }, { "descriptor": "Case-Control Studies", "descriptor_ui": "D016022", "major_topic": false }, { "descriptor": "Diet", "descriptor_ui": "D004032", "major_topic": true }, { "descriptor": "ErbB Receptors", "descriptor_ui": "D066246", "major_topic": false }, { "descriptor": "Feeding Behavior", "descriptor_ui": "D005247", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Japan", "descriptor_ui": "D007564", "major_topic": false }, { "descriptor": "Lung Neoplasms", "descriptor_ui": "D008175", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": false }, { "descriptor": "Risk Factors", "descriptor_ui": "D012307", "major_topic": false }, { "descriptor": "Soy Foods", "descriptor_ui": "D045730", "major_topic": true } ], "publication": { "conference_name": null, "date": "2008 Jun", "date_precision": "unknown", "issue": "6", "normalized_date": null, "pages": "1202-1208", "proceedings_title": null, "publisher": "", "title": "Cancer science", "volume": "99", "year": 2008 }, "ssbd": { "database": [], "repository": [] }, "title": "Soy consumption reduces the risk of non-small-cell lung cancers with epidermal growth factor receptor mutations among Japanese.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "We demonstrate dynamic imaging of molecular distribution in unstained living cells using Raman scattering. By combining slit-scanning detection and optimizing the excitation wavelength, we imaged the dynamic molecular distributions of cytochrome c, protein beta sheets, and lipids in unstained HeLa cells with a temporal resolution of 3 minutes. We found that 532-nm excitation can be used to generate strong Raman scattering signals and to suppress autofluorescence that typically obscures Raman signals. With this technique, we reveal time-resolved distributions of cytochrome c and other biomolecules in living cells in the process of cytokinesis without the need for fluorescent labels or markers.", "classifications": [ { "id": "Fujita", "label": "Group Fujita", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Keisaku", "last_name": "Hamada", "name": null }, { "creator_type": "author", "first_name": "Katsumasa", "last_name": "Fujita", "name": null }, { "creator_type": "author", "first_name": "Nicholas Isaac", "last_name": "Smith", "name": null }, { "creator_type": "author", "first_name": "Minoru", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Inouye", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Kawata", "name": null } ], "identifiers": { "doi": { "normalized": "10.1117/1.2952192" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "19021354" } }, "mesh": [ { "descriptor": "Biopolymers", "descriptor_ui": "D001704", "major_topic": false }, { "descriptor": "HeLa Cells", "descriptor_ui": "D006367", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Microscopy", "descriptor_ui": "D008853", "major_topic": false }, { "descriptor": "Molecular Probe Techniques", "descriptor_ui": "D015336", "major_topic": true }, { "descriptor": "Spectrum Analysis, Raman", "descriptor_ui": "D013059", "major_topic": false } ], "publication": { "conference_name": null, "date": "2008 Jul-Aug", "date_precision": "unknown", "issue": "4", "normalized_date": null, "pages": "044027", "proceedings_title": null, "publisher": "", "title": "Journal of biomedical optics", "volume": "13", "year": 2008 }, "ssbd": { "database": [], "repository": [] }, "title": "Raman microscopy for dynamic molecular imaging of living cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Centrosome positioning is actively regulated by forces acting on microtubules radiating from the centrosomes. Two mechanisms, center-directed and polarized cortical pulling, are major contributors to the successive centering and posteriorly displacing migrations of the centrosomes in single-cell–stage Caenorhabditis elegans. In this study, we analyze the spatial distribution of the forces acting on the centrosomes to examine the mechanism that switches centrosomal migration from centering to displacing. We clarify the spatial distribution of the forces using image processing to measure the micrometer-scale movements of the centrosomes. The changes in distribution show that polarized cortical pulling functions during centering migration. The polarized cortical pulling force directed posteriorly is repressed predominantly in the lateral regions during centering migration and is derepressed during posteriorly displacing migration. Computer simulations show that this local repression of cortical pulling force is sufficient for switching between centering and displacing migration. Local regulation of cortical pulling might be a mechanism conserved for the precise temporal regulation of centrosomal dynamic positioning.", "classifications": [ { "id": "Onami", "label": "Group Onami", "parent": "Fujiwara", "type": "group" }, { "id": "Fujiwara", "label": "Team Fujiwara", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Akatsuki", "last_name": "Kimura", "name": null }, { "creator_type": "author", "first_name": "Shuichi", "last_name": "Onami", "name": null } ], "identifiers": { "doi": { "normalized": "10.1083/jcb.200706005" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "18158330" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Biomechanical Phenomena", "descriptor_ui": "D001696", "major_topic": false }, { "descriptor": "Caenorhabditis elegans", "descriptor_ui": "D017173", "major_topic": false }, { "descriptor": "Cell Division", "descriptor_ui": "D002455", "major_topic": false }, { "descriptor": "Cell Movement", "descriptor_ui": "D002465", "major_topic": false }, { "descriptor": "Cell Nucleus", "descriptor_ui": "D002467", "major_topic": false }, { "descriptor": "Cell Polarity", "descriptor_ui": "D016764", "major_topic": false }, { "descriptor": "Centrosome", "descriptor_ui": "D018385", "major_topic": false }, { "descriptor": "Computer Simulation", "descriptor_ui": "D003198", "major_topic": false }, { "descriptor": "Cytoplasm", "descriptor_ui": "D003593", "major_topic": false }, { "descriptor": "Microtubules", "descriptor_ui": "D008870", "major_topic": false }, { "descriptor": "Models, Biological", "descriptor_ui": "D008954", "major_topic": false }, { "descriptor": "Models, Theoretical", "descriptor_ui": "D008962", "major_topic": false }, { "descriptor": "Spindle Apparatus", "descriptor_ui": "D008941", "major_topic": false }, { "descriptor": "Tensile Strength", "descriptor_ui": "D013718", "major_topic": false }, { "descriptor": "Weight-Bearing", "descriptor_ui": "D016474", "major_topic": false } ], "publication": { "conference_name": null, "date": "2007 Dec 31", "date_precision": "day", "issue": "7", "normalized_date": "2007-12-31", "pages": "1347-1354", "proceedings_title": null, "publisher": "", "title": "The Journal of Cell Biology", "volume": "179", "year": 2007 }, "ssbd": { "database": [], "repository": [] }, "title": "Local cortical pulling-force repression switches centrosomal centration and posterior displacement in C. elegans.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "", "classifications": [ { "id": "Sodeoka", "label": "Group Sodeoka", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Go", "last_name": "Hirai", "name": null }, { "creator_type": "author", "first_name": "Toru", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Kazunori", "last_name": "Yamaguchi", "name": null }, { "creator_type": "author", "first_name": "Taeko", "last_name": "Miyagi", "name": null }, { "creator_type": "author", "first_name": "Mikiko", "last_name": "Sodeoka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/ja075738w" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "18034482" } }, "mesh": [ { "descriptor": "Fluorocarbons", "descriptor_ui": "D005466", "major_topic": false }, { "descriptor": "Gangliosides", "descriptor_ui": "D005732", "major_topic": false }, { "descriptor": "Molecular Structure", "descriptor_ui": "D015394", "major_topic": false }, { "descriptor": "Stereoisomerism", "descriptor_ui": "D013237", "major_topic": false }, { "descriptor": "Sugar Acids", "descriptor_ui": "D013400", "major_topic": false } ], "publication": { "conference_name": null, "date": "2007 Dec 19", "date_precision": "day", "issue": "50", "normalized_date": "2007-12-19", "pages": "15420-15421", "proceedings_title": null, "publisher": "", "title": "Journal of the American Chemical Society", "volume": "129", "year": 2007 }, "ssbd": { "database": [], "repository": [] }, "title": "Stereocontrolled and convergent entry to CF2-sialosides: synthesis of CF2-linked ganglioside GM4.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "A convenient, rapid, and efficient method for the preparation of carbamates from amines with 1-alkoxycarbonyl-3-nitro-1,2,4-triazole transfer reagents is reported. Reactions of newly synthesized stable crystalline reagents with alkyl amines were completed in a few minutes without any additional base, and highly pure carbamates were obtained without chromatographic purification. These highly active reagents are also useful for the selective protection of nucleobases and preparation of carbonates and thiocarbonates.", "classifications": [ { "id": "Sodeoka", "label": "Group Sodeoka", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Mamoru", "last_name": "Shimizu", "name": null }, { "creator_type": "author", "first_name": "Mikiko", "last_name": "Sodeoka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/ol7024108" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "18001043" } }, "mesh": [ { "descriptor": "Alcohols", "descriptor_ui": "D000438", "major_topic": false }, { "descriptor": "Amines", "descriptor_ui": "D000588", "major_topic": false }, { "descriptor": "Carbamates", "descriptor_ui": "D002219", "major_topic": false }, { "descriptor": "Carbonates", "descriptor_ui": "D002254", "major_topic": false }, { "descriptor": "Crystallography, X-Ray", "descriptor_ui": "D018360", "major_topic": false }, { "descriptor": "Models, Molecular", "descriptor_ui": "D008958", "major_topic": false }, { "descriptor": "Molecular Structure", "descriptor_ui": "D015394", "major_topic": false }, { "descriptor": "Sulfhydryl Compounds", "descriptor_ui": "D013438", "major_topic": false } ], "publication": { "conference_name": null, "date": "2007 Dec 6", "date_precision": "day", "issue": "25", "normalized_date": "2007-12-06", "pages": "5231-5234", "proceedings_title": null, "publisher": "", "title": "Organic letters", "volume": "9", "year": 2007 }, "ssbd": { "database": [], "repository": [] }, "title": "Convenient method for the preparation of carbamates, carbonates, and thiocarbonates.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "We demonstrate the use of saturated excitation in confocal fluorescence microscopy to improve the spatial resolution. In the proposed technique, we modulate the excitation intensity temporally and detect the harmonic modulation of the fluorescence signal which is caused by the saturated excitation in the center of the laser focus. Theoretical and experimental investigations show that the demodulated fluorescence signal is nonlinearly proportional to the excitation intensity and contributes to improve the spatial resolution in three dimensions beyond the diffraction limit of light.", "classifications": [ { "id": "Fujita", "label": "Group Fujita", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Katsumasa", "last_name": "Fujita", "name": null }, { "creator_type": "author", "first_name": "Minoru", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Shogo", "last_name": "Kawano", "name": null }, { "creator_type": "author", "first_name": "Masahito", "last_name": "Yamanaka", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Kawata", "name": null } ], "identifiers": { "doi": { "normalized": "10.1103/physrevlett.99.228105" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "18233334" } }, "mesh": [ { "descriptor": "Fluorescence", "descriptor_ui": "D005453", "major_topic": false }, { "descriptor": "Microscopy, Confocal", "descriptor_ui": "D018613", "major_topic": false }, { "descriptor": "Microscopy, Fluorescence", "descriptor_ui": "D008856", "major_topic": false } ], "publication": { "conference_name": null, "date": "2007 Nov 30", "date_precision": "day", "issue": "22", "normalized_date": "2007-11-30", "pages": "228105", "proceedings_title": null, "publisher": "", "title": "Physical review letters", "volume": "99", "year": 2007 }, "ssbd": { "database": [], "repository": [] }, "title": "High-resolution confocal microscopy by saturated excitation of fluorescence.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Capillary electrophoresis (CE)-mass spectrometry (MS), as an analytical platform, has made significant contributions in advancing metabolomics research, if still limited up to this time. This review, covering reports published between 1998 and 2006, describes how CE-MS has been used thus far in this field, with the majority of the works dealing with targeted metabolite analyses and only a small fraction using it in the comprehensive context. It also discusses how some of the key features of CE-MS were exploited in selected metabolomic applications.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Maria Rowena N.", "last_name": "Monton", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.chroma.2007.02.065" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "17376458" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Bacteria", "descriptor_ui": "D001419", "major_topic": false }, { "descriptor": "Biomarkers", "descriptor_ui": "D015415", "major_topic": false }, { "descriptor": "Diagnosis", "descriptor_ui": "D003933", "major_topic": false }, { "descriptor": "Electrophoresis, Capillary", "descriptor_ui": "D019075", "major_topic": true }, { "descriptor": "Food Analysis", "descriptor_ui": "D005504", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mass Spectrometry", "descriptor_ui": "D013058", "major_topic": true }, { "descriptor": "Metabolism", "descriptor_ui": "D008660", "major_topic": true }, { "descriptor": "Systems Biology", "descriptor_ui": "D049490", "major_topic": false } ], "publication": { "conference_name": null, "date": "2007 Oct 19", "date_precision": "day", "issue": "1-2", "normalized_date": "2007-10-19", "pages": "237-246; discussion 236", "proceedings_title": null, "publisher": "", "title": "Journal of chromatography. A", "volume": "1168", "year": 2007 }, "ssbd": { "database": [], "repository": [] }, "title": "Metabolome analysis by capillary electrophoresis-mass spectrometry.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "An easy-to-implement capillary coating strategy based on polymer entrapment in the network of polymerized silicate is described. In this manner, cationic polymers are tightly fixed onto the inner wall of the capillary for electroosmotic flow control without necessitating complex surface modification chemistries. The resulting coated capillary exhibited good stability over a wide range of pH, good reproducibility, strong endurance in more than 300 electrophoretic runs, and tolerance of commonly employed organic solvent additives in CE. Applications in CE-MS analysis of biologically important anions as well as sample enrichment are shown. Additionally, it was used as a durable base for attachment of multiple layers of charged polymers on the wall, via electrostatic interaction with the preceding layer. Thus, two novel types of highly stable coated capillaries, one with anodic EOF and the other cathodic, were developed.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Maria Rowena N.", "last_name": "Monton", "name": null }, { "creator_type": "author", "first_name": "Masaru", "last_name": "Tomita", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Ishihama", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/ac071038y" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "17824669" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Anions", "descriptor_ui": "D000838", "major_topic": false }, { "descriptor": "Electrophoresis, Capillary", "descriptor_ui": "D019075", "major_topic": false }, { "descriptor": "Hydrogen-Ion Concentration", "descriptor_ui": "D006863", "major_topic": false }, { "descriptor": "Mass Spectrometry", "descriptor_ui": "D013058", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Microscopy, Electron, Scanning", "descriptor_ui": "D008855", "major_topic": false }, { "descriptor": "NIH 3T3 Cells", "descriptor_ui": "D041681", "major_topic": false }, { "descriptor": "Osmotic Pressure", "descriptor_ui": "D009997", "major_topic": false }, { "descriptor": "Polymers", "descriptor_ui": "D011108", "major_topic": false }, { "descriptor": "Reproducibility of Results", "descriptor_ui": "D015203", "major_topic": false }, { "descriptor": "Silicates", "descriptor_ui": "D017640", "major_topic": false } ], "publication": { "conference_name": null, "date": "2007 Oct 15", "date_precision": "day", "issue": "20", "normalized_date": "2007-10-15", "pages": "7838-7844", "proceedings_title": null, "publisher": "", "title": "Analytical chemistry", "volume": "79", "year": 2007 }, "ssbd": { "database": [], "repository": [] }, "title": "Polymer entrapment in polymerized silicate for preparing highly stable capillary coatings for CE and CE-MS.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Sustained elevation of [Ca(2+)](i) has been implicated in many cellular events. We previously reported that alpha subunits of G(12) family G proteins (Galpha(12/13)) participate in sustained Ca(2+) influx required for the activation of nuclear factor of activated T cells (NFAT), a Ca(2+)-responsive transcriptional factor, in rat neonatal cardiac fibroblasts. Here, we demonstrate that Galpha(12/13)-mediated up-regulation of canonical transient receptor potential 6 (TRPC6) channels participates in sustained Ca(2+) influx and NFAT activation by endothelin (ET)-1 treatment. Expression of constitutively active Galpha(12) or Galpha(13) increased the expression of TRPC6 proteins and basal Ca(2+) influx activity. The treatment with ET-1 increased TRPC6 protein levels through Galpha(12/13), reactive oxygen species, and c-Jun N-terminal kinase (JNK)-dependent pathways. NFAT is activated by sustained increase in [Ca(2+)](i) through up-regulated TRPC6. A Galpha(12/13)-inhibitory polypeptide derived from the regulator of the G-protein signaling domain of p115-Rho guanine nucleotide exchange factor and a JNK inhibitor, SP600125, suppressed the ET-1-induced increase in expression of marker proteins of myofibroblast formation through a Galpha(12/13)-reactive oxygen species-JNK pathway. The ET-1-induced myofibroblast formation was suppressed by overexpression of TRPC6 and CA NFAT, whereas it was enhanced by TRPC6 small interfering RNAs and cyclosporine A. These results suggest two opposite roles of Galpha(12/13) in cardiac fibroblasts. First, Galpha(12/13) mediate ET-1-induced myofibroblast formation. Second, Galpha(12/13) mediate TRPC6 up-regulation and NFAT activation that negatively regulates ET-1-induced myofibroblast formation. Furthermore, TRPC6 mediates hypertrophic responses in cardiac myocytes but suppresses fibrotic responses in cardiac fibroblasts. Thus, TRPC6 mediates opposite responses in cardiac myocytes and fibroblasts.", "classifications": [ { "id": "Nishida", "label": "Group Nishida", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Motohiro", "last_name": "Nishida", "name": null }, { "creator_type": "author", "first_name": "Naoya", "last_name": "Onohara", "name": null }, { "creator_type": "author", "first_name": "Yoji", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Reiko", "last_name": "Suda", "name": null }, { "creator_type": "author", "first_name": "Mariko", "last_name": "Ogushi", "name": null }, { "creator_type": "author", "first_name": "Shihori", "last_name": "Tanabe", "name": null }, { "creator_type": "author", "first_name": "Ryuji", "last_name": "Inoue", "name": null }, { "creator_type": "author", "first_name": "Yasuo", "last_name": "Mori", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Kurose", "name": null } ], "identifiers": { "doi": { "normalized": "10.1074/jbc.m611780200" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "17533154" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Collagen", "descriptor_ui": "D003094", "major_topic": false }, { "descriptor": "Endothelin-1", "descriptor_ui": "D019332", "major_topic": false }, { "descriptor": "Enzyme Inhibitors", "descriptor_ui": "D004791", "major_topic": false }, { "descriptor": "Fibroblasts", "descriptor_ui": "D005347", "major_topic": false }, { "descriptor": "GTP-Binding Protein alpha Subunits, G12-G13", "descriptor_ui": "D044365", "major_topic": false }, { "descriptor": "JNK Mitogen-Activated Protein Kinases", "descriptor_ui": "D048031", "major_topic": false }, { "descriptor": "Models, Biological", "descriptor_ui": "D008954", "major_topic": false }, { "descriptor": "Muscle Cells", "descriptor_ui": "D032342", "major_topic": false }, { "descriptor": "Myocardium", "descriptor_ui": "D009206", "major_topic": false }, { "descriptor": "NFATC Transcription Factors", "descriptor_ui": "D050778", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Rats, Sprague-Dawley", "descriptor_ui": "D017207", "major_topic": false }, { "descriptor": "TRPC Cation Channels", "descriptor_ui": "D050052", "major_topic": false }, { "descriptor": "Up-Regulation", "descriptor_ui": "D015854", "major_topic": true } ], "publication": { "conference_name": null, "date": "2007 Aug 10", "date_precision": "day", "issue": "32", "normalized_date": "2007-08-10", "pages": "23117-23128", "proceedings_title": null, "publisher": "", "title": "The Journal of biological chemistry", "volume": "282", "year": 2007 }, "ssbd": { "database": [], "repository": [] }, "title": "Galpha12/13-mediated up-regulation of TRPC6 negatively regulates endothelin-1-induced cardiac myofibroblast formation and collagen synthesis through nuclear factor of activated T cells activation.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "A method for the determination of nucleotides based on pressure-assisted capillary electrophoresis-electrospray ionization mass spectrometry (PACE-MS) is described. To prevent multi-phosphorylated species from adsorbing onto the fused-silica capillary, silanol groups were masked with phosphate ions by preconditioning the capillary with the background electrolyte containing phosphate. During preconditioning, nebulizer gas was turned off to avoid contamination of MS detector with phosphate ions. To detect nucleotides using the CE positive mode at a pH 7.5, it was necessary to apply air pressure to the inlet capillary during electrophoresis to supplement the electroosmotic flow (EOF) toward the cathode. Moreover, we exchanged the running electrolyte every analysis using the buffer replenishment system to obtain the required reproducibility. Under the optimized conditions, 14 phosphorylated species such as nucleotides, nicotinamide-adenine dinucleotides and coenzyme A (CoA) compounds were well determined in less than 20 min. The relative standard deviations (n=6) of the method were better than 0.9% for migration times and between 1.7% and 8.1% for peak areas. The detection limits for these species were between 0.5 and 1.7 micromol/L with pressure injection of 50 mbar for 30 s (30 nL) at a signal-to-noise ratio of 3. This approach is robust and quantitative compared to the previous method, and its utility is demonstrated by the analysis of intracellular nucleotides and CoA compounds extracted from Escherichia coli wild type, pfkA and pfkB knockout mutants. The methodology was used to suggest that pfkA is the main functional enzyme.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Takamasa", "last_name": "Ishikawa", "name": null }, { "creator_type": "author", "first_name": "Saori", "last_name": "Igarashi", "name": null }, { "creator_type": "author", "first_name": "Kaori", "last_name": "Sugawara", "name": null }, { "creator_type": "author", "first_name": "Yuji", "last_name": "Kakazu", "name": null }, { "creator_type": "author", "first_name": "Masaru", "last_name": "Tomita", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.chroma.2007.05.054" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "17543971" } }, "mesh": [ { "descriptor": "Coenzyme A", "descriptor_ui": "D003065", "major_topic": false }, { "descriptor": "Electrolytes", "descriptor_ui": "D004573", "major_topic": false }, { "descriptor": "Electroosmosis", "descriptor_ui": "D053841", "major_topic": false }, { "descriptor": "Electrophoresis, Capillary", "descriptor_ui": "D019075", "major_topic": false }, { "descriptor": "Escherichia coli Proteins", "descriptor_ui": "D029968", "major_topic": false }, { "descriptor": "Nucleotides", "descriptor_ui": "D009711", "major_topic": false }, { "descriptor": "Phosphates", "descriptor_ui": "D010710", "major_topic": false }, { "descriptor": "Pressure", "descriptor_ui": "D011312", "major_topic": false }, { "descriptor": "Reproducibility of Results", "descriptor_ui": "D015203", "major_topic": false }, { "descriptor": "Sensitivity and Specificity", "descriptor_ui": "D012680", "major_topic": false }, { "descriptor": "Silanes", "descriptor_ui": "D012821", "major_topic": false }, { "descriptor": "Spectrometry, Mass, Electrospray Ionization", "descriptor_ui": "D021241", "major_topic": false }, { "descriptor": "Systems Integration", "descriptor_ui": "D018511", "major_topic": false } ], "publication": { "conference_name": null, "date": "2007 Aug 3", "date_precision": "day", "issue": "1-2", "normalized_date": "2007-08-03", "pages": "125-133", "proceedings_title": null, "publisher": "", "title": "Journal of chromatography. A", "volume": "1159", "year": 2007 }, "ssbd": { "database": [], "repository": [] }, "title": "Analysis of nucleotides by pressure-assisted capillary electrophoresis-mass spectrometry using silanol mask technique.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "We have developed a metabolic flux analysis method that is based on (13)C-labeling patterns of the intracellular metabolites directly measured by capillary electrophoresis time-of-flight mass spectrometry (CE-TOFMS). The flux distribution of the central carbon metabolism in Escherichia coli was determined by this new approach and the results were compared with findings obtained by conventional GC-MS analysis based on isotopomer of the proteinogenic amino acids. There were some differences in estimation results between new approach using CE-TOFMS and conventional approach using GC-MS. These were thought to be attributable to variations in measured mass distributions between amino acids and the corresponding precursors and to differences in the sensitivity of the exchange coefficients to mass distributions. However, our CE-TOFMS method facilitates high-throughput flux analysis without requiring complicated sample preparation such as hydrolysis of proteins and derivatization of amino acids.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yoshihiro", "last_name": "Toya", "name": null }, { "creator_type": "author", "first_name": "Nobuyoshi", "last_name": "Ishii", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Hirasawa", "name": null }, { "creator_type": "author", "first_name": "Miki", "last_name": "Naba", "name": null }, { "creator_type": "author", "first_name": "Kenta", "last_name": "Hirai", "name": null }, { "creator_type": "author", "first_name": "Kaori", "last_name": "Sugawara", "name": null }, { "creator_type": "author", "first_name": "Saori", "last_name": "Igarashi", "name": null }, { "creator_type": "author", "first_name": "Kazuyuki", "last_name": "Shimizu", "name": null }, { "creator_type": "author", "first_name": "Masaru", "last_name": "Tomita", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.chroma.2007.04.011" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "17462663" } }, "mesh": [ { "descriptor": "Biosynthetic Pathways", "descriptor_ui": "D053898", "major_topic": false }, { "descriptor": "Carbon", "descriptor_ui": "D002244", "major_topic": false }, { "descriptor": "Carbon Isotopes", "descriptor_ui": "D002247", "major_topic": false }, { "descriptor": "Data Interpretation, Statistical", "descriptor_ui": "D003627", "major_topic": false }, { "descriptor": "Electrophoresis, Capillary", "descriptor_ui": "D019075", "major_topic": false }, { "descriptor": "Escherichia coli", "descriptor_ui": "D004926", "major_topic": false }, { "descriptor": "Escherichia coli Proteins", "descriptor_ui": "D029968", "major_topic": false }, { "descriptor": "Gas Chromatography-Mass Spectrometry", "descriptor_ui": "D008401", "major_topic": false }, { "descriptor": "Isotope Labeling", "descriptor_ui": "D007553", "major_topic": false }, { "descriptor": "Reproducibility of Results", "descriptor_ui": "D015203", "major_topic": false }, { "descriptor": "Sensitivity and Specificity", "descriptor_ui": "D012680", "major_topic": false }, { "descriptor": "Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization", "descriptor_ui": "D019032", "major_topic": false } ], "publication": { "conference_name": null, "date": "2007 Aug 3", "date_precision": "day", "issue": "1-2", "normalized_date": "2007-08-03", "pages": "134-141", "proceedings_title": null, "publisher": "", "title": "Journal of chromatography. A", "volume": "1159", "year": 2007 }, "ssbd": { "database": [], "repository": [] }, "title": "Direct measurement of isotopomer of intracellular metabolites using capillary electrophoresis time-of-flight mass spectrometry for efficient metabolic flux analysis.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "We examined the origin of individuality of two daughter cells born from an isolated single Escherichia coli mother cell during its cell division process by monitoring the change in its swimming behavior and tumbling frequency using an on-chip single-cell cultivation system. By keeping the isolated condition of an observed single cell, we compared its growth and swimming property within a generation and over up to seven generations. It revealed that running speed decreased as cell length smoothly increased within each generation, whereas tumbling frequency fluctuated among generations. Also found was an extraordinary tumbling mode characterized by the prolonged duration of pausing in predivisional cells after cell constriction. The observed prolonged pausing may imply the coexistence of two distinct control systems in a predivisional cell, indicating that individuality of daughter cells emerges after a mother cell initiates constriction and before it gets physically separated into two new cell bodies.", "classifications": [ { "id": "Wakamoto", "label": "Group Wakamoto", "parent": "Wakamoto", "type": "group" }, { "id": "Wakamoto", "label": "Team Wakamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Senkei", "last_name": "Umehara", "name": null }, { "creator_type": "author", "first_name": "Ippei", "last_name": "Inoue", "name": null }, { "creator_type": "author", "first_name": "Yuichi", "last_name": "Wakamoto", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Yasuda", "name": null } ], "identifiers": { "doi": { "normalized": "10.1529/biophysj.106.098061" }, "pmcid": { "normalized": "PMC1913147" }, "pmid": { "normalized": "17496044" } }, "mesh": [ { "descriptor": "Bacteria", "descriptor_ui": "D001419", "major_topic": false }, { "descriptor": "Bacterial Physiological Phenomena", "descriptor_ui": "D018407", "major_topic": false }, { "descriptor": "Cell Culture Techniques", "descriptor_ui": "D018929", "major_topic": false }, { "descriptor": "Cell Division", "descriptor_ui": "D002455", "major_topic": false }, { "descriptor": "Cell Movement", "descriptor_ui": "D002465", "major_topic": false }, { "descriptor": "Cells", "descriptor_ui": "D002477", "major_topic": false }, { "descriptor": "Genes, Reporter", "descriptor_ui": "D017930", "major_topic": false }, { "descriptor": "Green Fluorescent Proteins", "descriptor_ui": "D049452", "major_topic": false }, { "descriptor": "Models, Biological", "descriptor_ui": "D008954", "major_topic": false }, { "descriptor": "Software", "descriptor_ui": "D012984", "major_topic": false } ], "publication": { "conference_name": null, "date": "2007 Aug 1", "date_precision": "day", "issue": "3", "normalized_date": "2007-08-01", "pages": "1061-1067", "proceedings_title": null, "publisher": "", "title": "Biophysical journal", "volume": "93", "year": 2007 }, "ssbd": { "database": [], "repository": [] }, "title": "Origin of individuality of two daughter cells during the division process examined by the simultaneous measurement of growth and swimming property using an on-chip single-cell cultivation system.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "", "classifications": [ { "id": "Nanbo", "label": "Group Nanbo", "parent": "Tsuchiya", "type": "group" }, { "id": "Tsuchiya", "label": "Team Tsuchiya", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Masakazu", "last_name": "Nambo", "name": null }, { "creator_type": "author", "first_name": "Ryoji", "last_name": "Noyori", "name": null }, { "creator_type": "author", "first_name": "Kenichiro", "last_name": "Itami", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/ja073042x" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "17567019" } }, "mesh": [], "publication": { "conference_name": null, "date": "2007 Jul 4", "date_precision": "day", "issue": "26", "normalized_date": "2007-07-04", "pages": "8080-8081", "proceedings_title": null, "publisher": "", "title": "Journal of the American Chemical Society", "volume": "129", "year": 2007 }, "ssbd": { "database": [], "repository": [] }, "title": "Rh-catalyzed arylation and alkenylation of C(60) using organoboron compounds.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Plk1, an evolutionarily conserved M phase kinase, associates with not only spindle poles but also kinetochores during prometaphase. However, the role of Plk1 at kinetochores has been poorly understood. Here we show that BubR1 mediates the action of Plk1 at kinetochores for proper chromosome alignment. Our results show that BubR1 colocalizes with Plk1 at kinetochores of unaligned chromosomes and physically interacts with Plk1 in prometaphase cells. Down-regulation of Plk1 by small interfering RNA abolished the mobility-shifted, hyperphosphorylated form of BubR1 in the prometaphase-arrested cells. In addition, BubR1 was phosphorylated by Plk1 in vitro at two Plk1 consensus sites in the kinase domain of BubR1. The add-back of either wild-type BubR1 or BubR1 2E, in which the two Plk1 phosphorylation sites were replaced by glutamic acids, but not that of BubR1 2A, an unphosphorylatable mutant, rescued the chromosome alignment defects in BubR1-deficient cells. Moreover, when both Plk1 and BubR1 were down-regulated, the add-back of BubR1 2E, but not that of wild-type BubR1, rescued the chromosome alignment defects. These results taken together suggest that Plk1 facilitates chromosome alignment during prometaphase through BubR1.", "classifications": [ { "id": "Toyoshima", "label": "Group Toyoshima", "parent": "Toyoshima", "type": "group" }, { "id": "Toyoshima", "label": "Team Toyoshima", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Shigeru", "last_name": "Matsumura", "name": null }, { "creator_type": "author", "first_name": "Fumiko", "last_name": "Toyoshima", "name": null }, { "creator_type": "author", "first_name": "Eisuke", "last_name": "Nishida", "name": null } ], "identifiers": { "doi": { "normalized": "10.1074/jbc.m611053200" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "17376779" } }, "mesh": [ { "descriptor": "Amino Acid Substitution", "descriptor_ui": "D019943", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Cycle Proteins", "descriptor_ui": "D018797", "major_topic": false }, { "descriptor": "Chlorocebus aethiops", "descriptor_ui": "D002522", "major_topic": false }, { "descriptor": "Chromosomes, Human", "descriptor_ui": "D002877", "major_topic": false }, { "descriptor": "COS Cells", "descriptor_ui": "D019556", "major_topic": false }, { "descriptor": "Down-Regulation", "descriptor_ui": "D015536", "major_topic": false }, { "descriptor": "HeLa Cells", "descriptor_ui": "D006367", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Kinetochores", "descriptor_ui": "D018386", "major_topic": false }, { "descriptor": "Metaphase", "descriptor_ui": "D008677", "major_topic": false }, { "descriptor": "Mutation, Missense", "descriptor_ui": "D020125", "major_topic": false }, { "descriptor": "Phosphorylation", "descriptor_ui": "D010766", "major_topic": false }, { "descriptor": "Polo-Like Kinase 1", "descriptor_ui": "D000097869", "major_topic": false }, { "descriptor": "Protein Kinases", "descriptor_ui": "D011494", "major_topic": false }, { "descriptor": "Protein Serine-Threonine Kinases", "descriptor_ui": "D017346", "major_topic": false }, { "descriptor": "Protein Structure, Tertiary", "descriptor_ui": "D017434", "major_topic": false }, { "descriptor": "Proto-Oncogene Proteins", "descriptor_ui": "D011518", "major_topic": false } ], "publication": { "conference_name": null, "date": "2007 May 18", "date_precision": "day", "issue": "20", "normalized_date": "2007-05-18", "pages": "15217-15227", "proceedings_title": null, "publisher": "", "title": "The Journal of biological chemistry", "volume": "282", "year": 2007 }, "ssbd": { "database": [], "repository": [] }, "title": "Polo-like kinase 1 facilitates chromosome alignment during prometaphase through BubR1.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Analysis of cellular components at multiple levels of biological information can provide valuable functional insights. We performed multiple high-throughput measurements to study the response of Escherichia coli cells to genetic and environmental perturbations. Analysis of metabolic enzyme gene disruptants revealed unexpectedly small changes in messenger RNA and proteins for most disruptants. Overall, metabolite levels were also stable, reflecting the rerouting of fluxes in the metabolic network. In contrast, E. coli actively regulated enzyme levels to maintain a stable metabolic state in response to changes in growth rate. E. coli thus seems to use complementary strategies that result in a metabolic network robust against perturbations.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Nobuyoshi", "last_name": "Ishii", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Nakahigashi", "name": null }, { "creator_type": "author", "first_name": "Tomoya", "last_name": "Baba", "name": null }, { "creator_type": "author", "first_name": "Martin", "last_name": "Robert", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Akio", "last_name": "Kanai", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Hirasawa", "name": null }, { "creator_type": "author", "first_name": "Miki", "last_name": "Naba", "name": null }, { "creator_type": "author", "first_name": "Kenta", "last_name": "Hirai", "name": null }, { "creator_type": "author", "first_name": "Aminul", "last_name": "Hoque", "name": null }, { "creator_type": "author", "first_name": "Pei Yee", "last_name": "Ho", "name": null }, { "creator_type": "author", "first_name": "Yuji", "last_name": "Kakazu", "name": null }, { "creator_type": "author", "first_name": "Kaori", "last_name": "Sugawara", "name": null }, { "creator_type": "author", "first_name": "Saori", "last_name": "Igarashi", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Harada", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Masuda", "name": null }, { "creator_type": "author", "first_name": "Naoyuki", "last_name": "Sugiyama", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Togashi", "name": null }, { "creator_type": "author", "first_name": "Miki", "last_name": "Hasegawa", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Takai", "name": null }, { "creator_type": "author", "first_name": "Katsuyuki", "last_name": "Yugi", "name": null }, { "creator_type": "author", "first_name": "Kazuharu", "last_name": "Arakawa", "name": null }, { "creator_type": "author", "first_name": "Nayuta", "last_name": "Iwata", "name": null }, { "creator_type": "author", "first_name": "Yoshihiro", "last_name": "Toya", "name": null }, { "creator_type": "author", "first_name": "Yoichi", "last_name": "Nakayama", "name": null }, { "creator_type": "author", "first_name": "Takaaki", "last_name": "Nishioka", "name": null }, { "creator_type": "author", "first_name": "Kazuyuki", "last_name": "Shimizu", "name": null }, { "creator_type": "author", "first_name": "Hirotada", "last_name": "Mori", "name": null }, { "creator_type": "author", "first_name": "Masaru", "last_name": "Tomita", "name": null } ], "identifiers": { "doi": { "normalized": "10.1126/science.1132067" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "17379776" } }, "mesh": [ { "descriptor": "Chromatography, Liquid", "descriptor_ui": "D002853", "major_topic": false }, { "descriptor": "Computational Biology", "descriptor_ui": "D019295", "major_topic": false }, { "descriptor": "Electrophoresis, Capillary", "descriptor_ui": "D019075", "major_topic": false }, { "descriptor": "Electrophoresis, Gel, Two-Dimensional", "descriptor_ui": "D015180", "major_topic": false }, { "descriptor": "Enzyme Induction", "descriptor_ui": "D004790", "major_topic": false }, { "descriptor": "Enzyme Repression", "descriptor_ui": "D004794", "major_topic": false }, { "descriptor": "Enzymes", "descriptor_ui": "D004798", "major_topic": false }, { "descriptor": "Escherichia coli", "descriptor_ui": "D004926", "major_topic": false }, { "descriptor": "Escherichia coli Proteins", "descriptor_ui": "D029968", "major_topic": false }, { "descriptor": "Gene Expression", "descriptor_ui": "D015870", "major_topic": false }, { "descriptor": "Genes, Bacterial", "descriptor_ui": "D005798", "major_topic": true }, { "descriptor": "Mass Spectrometry", "descriptor_ui": "D013058", "major_topic": false }, { "descriptor": "Metabolic Networks and Pathways", "descriptor_ui": "D053858", "major_topic": true }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": false }, { "descriptor": "Oligonucleotide Array Sequence Analysis", "descriptor_ui": "D020411", "major_topic": false }, { "descriptor": "Proteome", "descriptor_ui": "D020543", "major_topic": false }, { "descriptor": "RNA, Messenger", "descriptor_ui": "D012333", "major_topic": false }, { "descriptor": "Systems Biology", "descriptor_ui": "D049490", "major_topic": false }, { "descriptor": "Transcription, Genetic", "descriptor_ui": "D014158", "major_topic": false } ], "publication": { "conference_name": null, "date": "2007 Apr 27", "date_precision": "day", "issue": "5824", "normalized_date": "2007-04-27", "pages": "593-597", "proceedings_title": null, "publisher": "", "title": "Science (New York, N.Y.)", "volume": "316", "year": 2007 }, "ssbd": { "database": [], "repository": [] }, "title": "Multiple high-throughput analyses monitor the response of E. coli to perturbations.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "When erythrocytes are exposed to hypoxia, hemoglobin (Hb) stabilizes in the T-state by capturing 2,3-bisphosphoglycerate. This process could reduce the intracellular pool of glycolytic substrates, jeopardizing cellular energetics. Recent observations suggest that hypoxia-induced activation of glycolytic enzymes is correlated with their release from Band III (BIII) on the cell membrane. Based on these data, we developed a mathematical model of erythrocyte metabolism and compared hypoxia-induced differences in predicted activities of the enzymes, their products, and cellular energetics between models with and without the interaction of Hb with BIII. The models predicted that the allostery-dependent Hb interaction with BIII accelerates consumption of upstream glycolytic substrates such as glucose 6-phosphate and increases downstream products such as phosphoenolpyruvate. This prediction was consistent with metabolomic data from capillary electrophoresis mass spectrometry. The hypoxia-induced alterations in the metabolites resulted from acceleration of glycolysis, as judged by increased conversion of [(13)C]glucose to [(13)C]lactate. The allostery-dependent interaction of Hb with BIII appeared to contribute not only to maintenance of energy charge but also to further synthesis of 2,3-bisphosphoglycerate, which could help sustain stabilization of T-state Hb during hypoxia. Furthermore, such an activation of glycolysis was not observed when Hb was stabilized in R-state by treating the cells with CO. These results suggest that Hb allostery in erythrocytes serves as an O(2)-sensing trigger that drives glycolytic acceleration to stabilize intracellular energetics and promote the ability to release O(2) from the cells.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Ayako", "last_name": "Kinoshita", "name": null }, { "creator_type": "author", "first_name": "Kosuke", "last_name": "Tsukada", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Takako", "last_name": "Hishiki", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Ueno", "name": null }, { "creator_type": "author", "first_name": "Yoichi", "last_name": "Nakayama", "name": null }, { "creator_type": "author", "first_name": "Masaru", "last_name": "Tomita", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Suematsu", "name": null } ], "identifiers": { "doi": { "normalized": "10.1074/jbc.m610717200" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "17289676" } }, "mesh": [ { "descriptor": "Carbon Monoxide", "descriptor_ui": "D002248", "major_topic": false }, { "descriptor": "Cell Hypoxia", "descriptor_ui": "D015687", "major_topic": false }, { "descriptor": "Erythrocytes", "descriptor_ui": "D004912", "major_topic": false }, { "descriptor": "Glycolysis", "descriptor_ui": "D006019", "major_topic": true }, { "descriptor": "Hemoglobins", "descriptor_ui": "D006454", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Models, Biological", "descriptor_ui": "D008954", "major_topic": true }, { "descriptor": "Oxygen", "descriptor_ui": "D010100", "major_topic": false }, { "descriptor": "Proteome", "descriptor_ui": "D020543", "major_topic": false } ], "publication": { "conference_name": null, "date": "2007 Apr 6", "date_precision": "day", "issue": "14", "normalized_date": "2007-04-06", "pages": "10731-10741", "proceedings_title": null, "publisher": "", "title": "The Journal of biological chemistry", "volume": "282", "year": 2007 }, "ssbd": { "database": [], "repository": [] }, "title": "Roles of hemoglobin Allostery in hypoxia-induced metabolic alterations in erythrocytes: simulation and its verification by metabolome analysis.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The orientation of mitotic spindles is tightly regulated in polarized cells, but it has been unclear whether there is a mechanism regulating spindle orientation in nonpolarized cells. Here we show that integrin-dependent cell adhesion to the substrate orients the mitotic spindle of nonpolarized cultured cells parallel to the substrate plane. The spindle is properly oriented in cells plated on fibronectin or collagen, but misoriented in cells on poly-L-lysine or treated with the RGD peptide or anti-β1-integrin antibody, indicating requirement of integrin-mediated cell adhesion for this mechanism. Remarkably, this mechanism is independent of gravitation or cell–cell adhesion, but requires actin cytoskeleton and astral microtubules. Furthermore, myosin X and the microtubule plus-end-tracking protein EB1 are shown to play a role in this mechanism through remodeling of actin cytoskeleton and stabilization of astral microtubules, respectively. Our results thus uncover the existence of a mechanism that orients the spindle parallel to the cell–substrate adhesion plane, and identify crucial factors involved in this novel mechanism.", "classifications": [ { "id": "Toyoshima", "label": "Group Toyoshima", "parent": "Toyoshima", "type": "group" }, { "id": "Toyoshima", "label": "Team Toyoshima", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Fumiko", "last_name": "Toyoshima", "name": null }, { "creator_type": "author", "first_name": "Eisuke", "last_name": "Nishida", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/sj.emboj.7601599" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "17318179" } }, "mesh": [ { "descriptor": "Actins", "descriptor_ui": "D000199", "major_topic": false }, { "descriptor": "Blotting, Western", "descriptor_ui": "D015153", "major_topic": false }, { "descriptor": "Cell Adhesion", "descriptor_ui": "D002448", "major_topic": false }, { "descriptor": "Cell Polarity", "descriptor_ui": "D016764", "major_topic": false }, { "descriptor": "DNA Primers", "descriptor_ui": "D017931", "major_topic": false }, { "descriptor": "HeLa Cells", "descriptor_ui": "D006367", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Integrin beta1", "descriptor_ui": "D019012", "major_topic": false }, { "descriptor": "Microtubule-Associated Proteins", "descriptor_ui": "D008869", "major_topic": false }, { "descriptor": "Myosins", "descriptor_ui": "D009218", "major_topic": false }, { "descriptor": "Reverse Transcriptase Polymerase Chain Reaction", "descriptor_ui": "D020133", "major_topic": false }, { "descriptor": "RNA, Small Interfering", "descriptor_ui": "D034741", "major_topic": false }, { "descriptor": "Spindle Apparatus", "descriptor_ui": "D008941", "major_topic": false } ], "publication": { "conference_name": null, "date": "2007 Mar 21", "date_precision": "day", "issue": "6", "normalized_date": "2007-03-21", "pages": "1487-1498", "proceedings_title": null, "publisher": "", "title": "The EMBO Journal", "volume": "26", "year": 2007 }, "ssbd": { "database": [], "repository": [] }, "title": "Integrin-mediated adhesion orients the spindle parallel to the substratum in an EB1- and myosin X-dependent manner.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: Density plot visualizations (also referred to as heat maps or color maps) are widely used in different fields including large-scale omics studies in biological sciences. However, the current color-codings limit the visualizations to single datasets or pairwise comparisons. RESULTS: We propose a color-coding approach for the representation of three-way comparisons. The approach is based on the HSB (hue, saturation, brightness) color model. The three compared values are assigned specific hue values from the circular hue range (e.g. red, green, and blue). The hue value representing the three-way comparison is calculated according to the distribution of three compared values. If two of the values are identical and one is different, the resulting hue is set to the characteristic hue of the differing value. If all three compared values are different, the resulting hue is selected from a color gradient running between the hues of the two most distant values (as measured by the absolute value of their difference) according to the relative position of the third value between the two. The saturation of the color representing the three-way comparison reflects the amplitude (or extent) of the numerical difference between the two most distant values according to a scale of interest. The brightness is set to a maximum value by default but can be used to encode additional information about the three-way comparison. CONCLUSION: We propose a novel color-coding approach for intuitive visualization of three-way comparisons of omics data.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Richard", "last_name": "Baran", "name": null }, { "creator_type": "author", "first_name": "Martin", "last_name": "Robert", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Suematsu", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Masaru", "last_name": "Tomita", "name": null } ], "identifiers": { "doi": { "normalized": "10.1186/1471-2105-8-72" }, "pmcid": { "normalized": "PMC1831488" }, "pmid": { "normalized": "17335588" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Computer Graphics", "descriptor_ui": "D003196", "major_topic": true }, { "descriptor": "Computer Simulation", "descriptor_ui": "D003198", "major_topic": false }, { "descriptor": "Databases, Genetic", "descriptor_ui": "D030541", "major_topic": true }, { "descriptor": "Genomics", "descriptor_ui": "D023281", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Models, Biological", "descriptor_ui": "D008954", "major_topic": true }, { "descriptor": "Proteome", "descriptor_ui": "D020543", "major_topic": false }, { "descriptor": "Software", "descriptor_ui": "D012984", "major_topic": true }, { "descriptor": "User-Computer Interface", "descriptor_ui": "D014584", "major_topic": true } ], "publication": { "conference_name": null, "date": "2007 Mar 5", "date_precision": "day", "issue": "", "normalized_date": "2007-03-05", "pages": "72", "proceedings_title": null, "publisher": "", "title": "BMC bioinformatics", "volume": "8", "year": 2007 }, "ssbd": { "database": [], "repository": [] }, "title": "Visualization of three-way comparisons of omics data.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "An efficient catalytic enantioselective fluorination of tert-butoxycarbonyl lactones and lactams is reported. Reactions of the lactone substrates proceeded smoothly in an alcoholic solvent with a catalytic amount of chiral Pd(II) complex. In the case of the less acidic lactam substrates, concurrent use of the Pd complex and 2,6-lutidine as a cocatalyst was effective. Under the reaction conditions, the fluorinated lactones and lactams were obtained in good yield with excellent enantioselectivity (94-99% ee).", "classifications": [ { "id": "Sodeoka", "label": "Group Sodeoka", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Toshiaki", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Tomomi", "last_name": "Goto", "name": null }, { "creator_type": "author", "first_name": "Yoshitaka", "last_name": "Hamashima", "name": null }, { "creator_type": "author", "first_name": "Mikiko", "last_name": "Sodeoka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/jo062048m" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "17194106" } }, "mesh": [ { "descriptor": "Amines", "descriptor_ui": "D000588", "major_topic": false }, { "descriptor": "Catalysis", "descriptor_ui": "D002384", "major_topic": false }, { "descriptor": "Fluorine", "descriptor_ui": "D005461", "major_topic": false }, { "descriptor": "Lactams", "descriptor_ui": "D007769", "major_topic": false }, { "descriptor": "Lactones", "descriptor_ui": "D007783", "major_topic": false }, { "descriptor": "Molecular Structure", "descriptor_ui": "D015394", "major_topic": false }, { "descriptor": "Palladium", "descriptor_ui": "D010165", "major_topic": false }, { "descriptor": "Phosphines", "descriptor_ui": "D010720", "major_topic": false }, { "descriptor": "Stereoisomerism", "descriptor_ui": "D013237", "major_topic": false } ], "publication": { "conference_name": null, "date": "2007 Jan 5", "date_precision": "day", "issue": "1", "normalized_date": "2007-01-05", "pages": "246-250", "proceedings_title": null, "publisher": "", "title": "The Journal of organic chemistry", "volume": "72", "year": 2007 }, "ssbd": { "database": [], "repository": [] }, "title": "Enantioselective fluorination of tert-butoxycarbonyl lactones and lactams catalyzed by chiral Pd(II)-bisphosphine complexes.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "", "classifications": [ { "id": "Sodeoka", "label": "Group Sodeoka", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Toshiaki", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Yoshitaka", "last_name": "Hamashima", "name": null }, { "creator_type": "author", "first_name": "Mikiko", "last_name": "Sodeoka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/anie.200701071" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "17568468" } }, "mesh": [ { "descriptor": "Acetates", "descriptor_ui": "D000085", "major_topic": false }, { "descriptor": "Catalysis", "descriptor_ui": "D002384", "major_topic": false }, { "descriptor": "Fluorine Compounds", "descriptor_ui": "D017611", "major_topic": false }, { "descriptor": "Molecular Structure", "descriptor_ui": "D015394", "major_topic": false }, { "descriptor": "Nickel", "descriptor_ui": "D009532", "major_topic": false }, { "descriptor": "Organometallic Compounds", "descriptor_ui": "D009942", "major_topic": false }, { "descriptor": "Oxides", "descriptor_ui": "D010087", "major_topic": false }, { "descriptor": "Pyridines", "descriptor_ui": "D011725", "major_topic": false }, { "descriptor": "Silicon Compounds", "descriptor_ui": "D017655", "major_topic": false }, { "descriptor": "Stereoisomerism", "descriptor_ui": "D013237", "major_topic": false } ], "publication": { "conference_name": null, "date": "2007", "date_precision": "year", "issue": "28", "normalized_date": "2007", "pages": "5435-5439", "proceedings_title": null, "publisher": "", "title": "Angewandte Chemie (International ed. in English)", "volume": "46", "year": 2007 }, "ssbd": { "database": [], "repository": [] }, "title": "Asymmetric fluorination of alpha-aryl acetic acid derivatives with the catalytic system NiCl2-Binap/R3SiOTf/2,6-lutidine.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "We have fabricated a coaxial sheath liquid flow microelectrospray ionization (microESI) interface for capillary electrophoresis coupled with mass spectrometry (CE/MS). The ESI interface, which features a reduced probe diameter (130 microm i.d. x 174 microm o.d.) with a nebulizer-free format, can relatively easily electrospray a large amount of make-up sheath liquid (5-10 microL/min) over the long term (more than 80 runs) with a high degree of stability. The interface also provides higher separation qualities and improved detection sensitivities compared with a conventional ion spray (IS) interface.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Masahiko", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Ishihama", "name": null }, { "creator_type": "author", "first_name": "Masaru", "last_name": "Tomita", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/rcm.3256" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "17935119" } }, "mesh": [ { "descriptor": "Electrophoresis, Capillary", "descriptor_ui": "D019075", "major_topic": false }, { "descriptor": "Equipment Design", "descriptor_ui": "D004867", "major_topic": false }, { "descriptor": "Nucleotides", "descriptor_ui": "D009711", "major_topic": false }, { "descriptor": "Reproducibility of Results", "descriptor_ui": "D015203", "major_topic": false }, { "descriptor": "Spectrometry, Mass, Electrospray Ionization", "descriptor_ui": "D021241", "major_topic": false } ], "publication": { "conference_name": null, "date": "2007", "date_precision": "year", "issue": "22", "normalized_date": "2007", "pages": "3579-3584", "proceedings_title": null, "publisher": "", "title": "Rapid communications in mass spectrometry : RCM", "volume": "21", "year": 2007 }, "ssbd": { "database": [], "repository": [] }, "title": "Microelectrospray interface with coaxial sheath flow for high-resolution capillary electrophoresis/mass spectrometry separation.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "A new approach for the comprehensive and quantitative analysis of charged metabolites by capillary electrophoresis-mass spectrometry (CE-MS) is described. Metabolites are first separated by CE based on charge and size, and then selectively detected using MS by monitoring ions over a large range of m/z values. This technique enables the simultaneous determination of over 1000 charged species, and it can readily be applied to various types of biological samples originating from bacteria, plants, mammals, body fluids, and others. This chapter highlights detailed practical procedures for using this technology.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null } ], "identifiers": { "doi": { "normalized": "10.1007/978-1-59745-244-1_8" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "17035684" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Anions", "descriptor_ui": "D000838", "major_topic": false }, { "descriptor": "Bacillus subtilis", "descriptor_ui": "D001412", "major_topic": false }, { "descriptor": "Cations", "descriptor_ui": "D002412", "major_topic": false }, { "descriptor": "Electrophoresis, Capillary", "descriptor_ui": "D019075", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mass Spectrometry", "descriptor_ui": "D013058", "major_topic": false }, { "descriptor": "Nucleotides", "descriptor_ui": "D009711", "major_topic": false }, { "descriptor": "Oryza", "descriptor_ui": "D012275", "major_topic": false } ], "publication": { "conference_name": null, "date": "2007", "date_precision": "year", "issue": "", "normalized_date": "2007", "pages": "129-137", "proceedings_title": null, "publisher": "", "title": "Methods in molecular biology (Clifton, N.J.)", "volume": "358", "year": 2007 }, "ssbd": { "database": [], "repository": [] }, "title": "Capillary electrophoresis-mass spectrometry for metabolomics.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "We demonstrate a time-lapse video approach that allows rapid examination of the spatio-temporal dynamics of Dictyostelium cell populations. Quantitative information was gathered by sampling life histories of more than 2,000 mutant clones from a large mutagenesis collection. Approximately 4% of the clonal lines showed a mutant phenotype at one stage. Many of these could be ordered by clustering into functional groups. The dataset allows one to search and retrieve movies on a gene-by-gene and phenotype-by-phenotype basis.", "classifications": [ { "id": "Sawai", "label": "Group Sawai", "parent": "Sawai", "type": "group" }, { "id": "Sawai", "label": "Team Sawai", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Satoshi", "last_name": "Sawai", "name": null }, { "creator_type": "author", "first_name": "Xiao-Juan", "last_name": "Guan", "name": null }, { "creator_type": "author", "first_name": "Adam", "last_name": "Kuspa", "name": null }, { "creator_type": "author", "first_name": "Edward C.", "last_name": "Cox", "name": null } ], "identifiers": { "doi": { "normalized": "10.1186/gb-2007-8-7-r144" }, "pmcid": { "normalized": "PMC2323234" }, "pmid": { "normalized": "17659086" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Dictyostelium", "descriptor_ui": "D004023", "major_topic": false }, { "descriptor": "Microscopy, Video", "descriptor_ui": "D018715", "major_topic": false }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": false }, { "descriptor": "Phenotype", "descriptor_ui": "D010641", "major_topic": false } ], "publication": { "conference_name": null, "date": "2007", "date_precision": "year", "issue": "7", "normalized_date": "2007", "pages": "R144", "proceedings_title": null, "publisher": "", "title": "Genome biology", "volume": "8", "year": 2007 }, "ssbd": { "database": [], "repository": [] }, "title": "High-throughput analysis of spatio-temporal dynamics in Dictyostelium.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Genome-wide array-based comparative genomic hybridization analysis of malignant pleural mesotheliomas (MPM) was carried out to identify regions that display DNA copy number alterations. Seventeen primary tumors and nine cell lines derived from 22 individuals were studied, some of them originating from the same patients. Regions of genomic aberrations observed in >20% of individuals were 1q, 5p, 7p, 8q24 and 20p with gains, and 1p36.33, 1p36.1, 1p21.3, 3p21.3, 4q22, 4q34-qter, 6q25, 9p21.3, 10p, 13q33.2, 14q32.13, 18q and 22q with losses. Two regions at 1p32.1 and 11q22 showed a high copy gain. The 1p32.1 region contained a protooncogene, JUN, and we further demonstrated overexpression of JUN with real-time polymerase chain reaction analysis. As MPM cell lines did not overexpress JUN, our findings suggested that induction of JUN expression was involved in the development of MPM cells in vivo, which also might result in gene amplification in a subset of MPM. Meanwhile, the most frequent alteration was the 9p21.3 deletion, which includes the p16(INK4a)/p14(ARF) locus. With polymerase chain reaction analysis, we determined the extent of the homozygous deletion regions of the p16(INK4a)/p14(ARF) locus in MPM cell lines, which indicated that the deletion regions varied among cell lines. Our results with array comparative genomic hybridization analysis provide new insights into the genetic background of MPM, and also give some clues to develop a new molecular target therapy for MPM.", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Tetsuo", "last_name": "Taniguchi", "name": null }, { "creator_type": "author", "first_name": "Sivasundaram", "last_name": "Karnan", "name": null }, { "creator_type": "author", "first_name": "Takayuki", "last_name": "Fukui", "name": null }, { "creator_type": "author", "first_name": "Toshihiko", "last_name": "Yokoyama", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Tagawa", "name": null }, { "creator_type": "author", "first_name": "Kohei", "last_name": "Yokoi", "name": null }, { "creator_type": "author", "first_name": "Yuichi", "last_name": "Ueda", "name": null }, { "creator_type": "author", "first_name": "Tetsuya", "last_name": "Mitsudomi", "name": null }, { "creator_type": "author", "first_name": "Yoshitsugu", "last_name": "Horio", "name": null }, { "creator_type": "author", "first_name": "Toyoaki", "last_name": "Hida", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null }, { "creator_type": "author", "first_name": "Masao", "last_name": "Seto", "name": null }, { "creator_type": "author", "first_name": "Yoshitaka", "last_name": "Sekido", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/j.1349-7006.2006.00386.x" }, "pmcid": { "normalized": "PMC11158069" }, "pmid": { "normalized": "17270034" } }, "mesh": [ { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Chromosome Aberrations", "descriptor_ui": "D002869", "major_topic": true }, { "descriptor": "Chromosome Mapping", "descriptor_ui": "D002874", "major_topic": false }, { "descriptor": "Chromosomes, Human, Pair 1", "descriptor_ui": "D002878", "major_topic": true }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Gene Dosage", "descriptor_ui": "D018628", "major_topic": false }, { "descriptor": "Gene Expression Profiling", "descriptor_ui": "D020869", "major_topic": true }, { "descriptor": "Genes, jun", "descriptor_ui": "D016758", "major_topic": true }, { "descriptor": "Genetic Markers", "descriptor_ui": "D005819", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mesothelioma", "descriptor_ui": "D008654", "major_topic": false }, { "descriptor": "Microsatellite Repeats", "descriptor_ui": "D018895", "major_topic": false }, { "descriptor": "Nucleic Acid Amplification Techniques", "descriptor_ui": "D021141", "major_topic": false }, { "descriptor": "Nucleic Acid Hybridization", "descriptor_ui": "D009693", "major_topic": false }, { "descriptor": "Oligonucleotide Array Sequence Analysis", "descriptor_ui": "D020411", "major_topic": false }, { "descriptor": "Pleural Neoplasms", "descriptor_ui": "D010997", "major_topic": false }, { "descriptor": "Polymerase Chain Reaction", "descriptor_ui": "D016133", "major_topic": false } ], "publication": { "conference_name": null, "date": "2007 Mar", "date_precision": "unknown", "issue": "3", "normalized_date": null, "pages": "438-446", "proceedings_title": null, "publisher": "", "title": "Cancer science", "volume": "98", "year": 2007 }, "ssbd": { "database": [], "repository": [] }, "title": "Genomic profiling of malignant pleural mesothelioma with array-based comparative genomic hybridization shows frequent non-random chromosomal alteration regions including JUN amplification on 1p32.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "", "classifications": [ { "id": "Nishida", "label": "Group Nishida", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Kurose", "name": null }, { "creator_type": "author", "first_name": "Motohiro", "last_name": "Nishida", "name": null } ], "identifiers": { "doi": { "normalized": null }, "pmcid": { "normalized": null }, "pmid": { "normalized": "18027573" } }, "mesh": [ { "descriptor": "Active Transport, Cell Nucleus", "descriptor_ui": "D021581", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Calcium", "descriptor_ui": "D002118", "major_topic": false }, { "descriptor": "Cardiomegaly", "descriptor_ui": "D006332", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "NFATC Transcription Factors", "descriptor_ui": "D050778", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "TRPC Cation Channels", "descriptor_ui": "D050052", "major_topic": false } ], "publication": { "conference_name": null, "date": "2007 Oct", "date_precision": "unknown", "issue": "10", "normalized_date": null, "pages": "953-956", "proceedings_title": null, "publisher": "", "title": "Seikagaku. The Journal of Japanese Biochemical Society", "volume": "79", "year": 2007 }, "ssbd": { "database": [], "repository": [] }, "title": "[TRPC channels and cardiac hypertrophy].", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Cultured adherent cells divide on the substratum, leading to formation of the cell monolayer. However, how the orientation of this anchorage-dependent cell division is regulated remains unknown. We have previously shown that integrin-dependent adhesion orients the spindle parallel to the substratum, which ensures this anchorage-dependent cell division. Here, we show that phosphatidylinositol-3,4,5-triphosphate (PtdIns(3,4,5)P3) is essential for this spindle orientation control. In metaphase, PtdIns(3,4,5)P3 is accumulated in the midcortex in an integrin-dependent manner. Inhibition of phosphatidylinositol-3-OH kinase (PI(3)K) reduces the accumulation of PtdIns(3,4,5)P3 and induces spindle misorientation. Introduction of PtdIns(3,4,5)P3 to these cells restores the midcortical accumulation of PtdIns(3,4,5)P3 and proper spindle orientation. PI(3)K inhibition causes dynein-dependent spindle rotations along the z-axis, resulting in spindle misorientation. Moreover, dynactin, a dynein-binding partner, is accumulated in the midcortex in a PtdIns(3,4,5)P3-dependent manner. We propose that PtdIns(3,4,5)P3 directs dynein/dynactin-dependent pulling forces on spindles to the midcortex, and thereby orients the spindle parallel to the substratum.", "classifications": [ { "id": "Toyoshima", "label": "Group Toyoshima", "parent": "Toyoshima", "type": "group" }, { "id": "Toyoshima", "label": "Team Toyoshima", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Fumiko", "last_name": "Toyoshima", "name": null }, { "creator_type": "author", "first_name": "Shigeru", "last_name": "Matsumura", "name": null }, { "creator_type": "author", "first_name": "Hiroko", "last_name": "Morimoto", "name": null }, { "creator_type": "author", "first_name": "Masaru", "last_name": "Mitsushima", "name": null }, { "creator_type": "author", "first_name": "Eisuke", "last_name": "Nishida", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.devcel.2007.10.014" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "18061563" } }, "mesh": [ { "descriptor": "Actins", "descriptor_ui": "D000199", "major_topic": false }, { "descriptor": "Cell Adhesion", "descriptor_ui": "D002448", "major_topic": false }, { "descriptor": "Cell Polarity", "descriptor_ui": "D016764", "major_topic": true }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Cytoskeleton", "descriptor_ui": "D003599", "major_topic": false }, { "descriptor": "Dynactin Complex", "descriptor_ui": "D000072159", "major_topic": false }, { "descriptor": "Dyneins", "descriptor_ui": "D004398", "major_topic": false }, { "descriptor": "HeLa Cells", "descriptor_ui": "D006367", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Immunoblotting", "descriptor_ui": "D015151", "major_topic": false }, { "descriptor": "Integrins", "descriptor_ui": "D016023", "major_topic": false }, { "descriptor": "Kidney Cortex", "descriptor_ui": "D007672", "major_topic": false }, { "descriptor": "Metaphase", "descriptor_ui": "D008677", "major_topic": false }, { "descriptor": "Microtubule-Associated Proteins", "descriptor_ui": "D008869", "major_topic": false }, { "descriptor": "Phosphatidylinositol 3-Kinases", "descriptor_ui": "D019869", "major_topic": false }, { "descriptor": "Phosphatidylinositol Phosphates", "descriptor_ui": "D018129", "major_topic": false }, { "descriptor": "PTEN Phosphohydrolase", "descriptor_ui": "D051059", "major_topic": false }, { "descriptor": "RNA, Small Interfering", "descriptor_ui": "D034741", "major_topic": false }, { "descriptor": "Spindle Apparatus", "descriptor_ui": "D008941", "major_topic": false }, { "descriptor": "Transfection", "descriptor_ui": "D014162", "major_topic": false } ], "publication": { "conference_name": null, "date": "2007 Dec", "date_precision": "unknown", "issue": "6", "normalized_date": null, "pages": "796-811", "proceedings_title": null, "publisher": "", "title": "Developmental cell", "volume": "13", "year": 2007 }, "ssbd": { "database": [], "repository": [] }, "title": "PtdIns(3,4,5)P3 regulates spindle orientation in adherent cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Preimplantation development is a crucial step for successful implantation and pregnancy. Although both compaction and blastocyst formation have been extensively studied, mechanisms regulating the early cell division stages before compaction have remained unclear. Here, we show that extracellular signal regulated kinase (ERK) mitogen-activated protein (MAP) kinase function is required for early embryonic cell division before compaction. Our analysis demonstrates that inhibition of ERK activation in late two-cell-stage embryos leads to a reversible arrest in the G2 phase at the four-cell stage. The G2-arrested four-cell-stage embryos showed weakened cell-cell adhesion as compared with control embryos. Remarkably, microarray analyses showed that most of the programmed changes of upregulated and downregulated gene expression during the four- to eight-cell stages proceeded normally in four-cell-stage-arrested embryos that were subsequently released to resume development; however, the expression profiles of a proportion of genes in these embryos closely paralleled the stages of embryonic rather than normal development. These parallel genes included the genes encoding intercellular adhesion molecules, whose expression appeared to be positively regulated by the ERK pathway. We also show that, whereas ERK inactivation in eight-cell-stage embryos did not lead to cell division arrest, it did cause this arrest when cadherin-mediated cell-cell adhesion was disrupted. These results demonstrate an essential role of ERK function in two-cell to eight-cell-stage embryos, and suggest a loose parallelism between the gene expression programs and the developmental stages before compaction.", "classifications": [ { "id": "Yamamoto", "label": "Group Yamamoto", "parent": "Toyoshima", "type": "group" }, { "id": "Toyoshima", "label": "Team Toyoshima", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Momoko", "last_name": "Maekawa", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Michiaki", "last_name": "Kohno", "name": null }, { "creator_type": "author", "first_name": "Masatoshi", "last_name": "Takeichi", "name": null }, { "creator_type": "author", "first_name": "Eisuke", "last_name": "Nishida", "name": null } ], "identifiers": { "doi": { "normalized": "10.1242/dev.003756" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "17611221" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Benzamides", "descriptor_ui": "D001549", "major_topic": false }, { "descriptor": "Butadienes", "descriptor_ui": "D002070", "major_topic": false }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Embryo Culture Techniques", "descriptor_ui": "D046149", "major_topic": false }, { "descriptor": "Embryonic Development", "descriptor_ui": "D047108", "major_topic": false }, { "descriptor": "ets-Domain Protein Elk-1", "descriptor_ui": "D050807", "major_topic": false }, { "descriptor": "Extracellular Signal-Regulated MAP Kinases", "descriptor_ui": "D048049", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Gene Expression Profiling", "descriptor_ui": "D020869", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred ICR", "descriptor_ui": "D008813", "major_topic": false }, { "descriptor": "Models, Biological", "descriptor_ui": "D008954", "major_topic": false }, { "descriptor": "Nitriles", "descriptor_ui": "D009570", "major_topic": false }, { "descriptor": "Oligonucleotide Array Sequence Analysis", "descriptor_ui": "D020411", "major_topic": false }, { "descriptor": "Phosphorylation", "descriptor_ui": "D010766", "major_topic": false }, { "descriptor": "Pregnancy", "descriptor_ui": "D011247", "major_topic": false } ], "publication": { "conference_name": null, "date": "2007 Aug", "date_precision": "unknown", "issue": "15", "normalized_date": null, "pages": "2751-2759", "proceedings_title": null, "publisher": "", "title": "Development (Cambridge, England)", "volume": "134", "year": 2007 }, "ssbd": { "database": [], "repository": [] }, "title": "Requirement for ERK MAP kinase in mouse preimplantation development.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Cell polarity is a general cellular process that can be seen in various cell types such as migrating neutrophils and Dictyostelium cells. The Rho small GTP(guanosine 5'-tri phosphate)ases have been shown to regulate cell polarity; however, its mechanism of emergence has yet to be clarified. We first developed a reaction-diffusion model of the Rho GTPases, which exhibits switch-like reversible response to a gradient of extracellular signals, exclusive accumulation of Cdc42 and Rac, or RhoA at the maximal or minimal intensity of the signal, respectively, and tracking of changes of a signal gradient by the polarized peak. The previous cell polarity models proposed by Subramanian and Narang show similar behaviors to our Rho GTPase model, despite the difference in molecular networks. This led us to compare these models, and we found that these models commonly share instability and a mass conservation of components. Based on these common properties, we developed conceptual models of a mass conserved reaction-diffusion system with diffusion-driven instability. These conceptual models retained similar behaviors of cell polarity in the Rho GTPase model. Using these models, we numerically and analytically found that multiple polarized peaks are unstable, resulting in a single stable peak (uniqueness of axis), and that sensitivity toward changes of a signal gradient is specifically restricted at the polarized peak (localized sensitivity). Although molecular networks may differ from one cell type to another, the behaviors of cell polarity in migrating cells seem similar, suggesting that there should be a fundamental principle. Thus, we propose that a mass conserved reaction-diffusion system with diffusion-driven instability is one of such principles of cell polarity.", "classifications": [ { "id": "Ishihara", "label": "Group Ishihara", "parent": "Sawai", "type": "group" }, { "id": "Kuroda", "label": "Group Kuroda", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" }, { "id": "Sawai", "label": "Team Sawai", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Mikiya", "last_name": "Otsuji", "name": null }, { "creator_type": "author", "first_name": "Shuji", "last_name": "Ishihara", "name": null }, { "creator_type": "author", "first_name": "Carl", "last_name": "Co", "name": null }, { "creator_type": "author", "first_name": "Kozo", "last_name": "Kaibuchi", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Mochizuki", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Kuroda", "name": null } ], "identifiers": { "doi": { "normalized": "10.1371/journal.pcbi.0030108" }, "pmcid": { "normalized": "PMC1892603" }, "pmid": { "normalized": "17559299" } }, "mesh": [ { "descriptor": "Cell Movement", "descriptor_ui": "D002465", "major_topic": false }, { "descriptor": "Cell Polarity", "descriptor_ui": "D016764", "major_topic": false }, { "descriptor": "Computer Simulation", "descriptor_ui": "D003198", "major_topic": false }, { "descriptor": "Diffusion", "descriptor_ui": "D004058", "major_topic": false }, { "descriptor": "Energy Transfer", "descriptor_ui": "D004735", "major_topic": false }, { "descriptor": "Models, Biological", "descriptor_ui": "D008954", "major_topic": true }, { "descriptor": "rho GTP-Binding Proteins", "descriptor_ui": "D020741", "major_topic": false } ], "publication": { "conference_name": null, "date": "2007 Jun", "date_precision": "unknown", "issue": "6", "normalized_date": null, "pages": "e108", "proceedings_title": null, "publisher": "", "title": "PLoS computational biology", "volume": "3", "year": 2007 }, "ssbd": { "database": [], "repository": [] }, "title": "A mass conserved reaction-diffusion system captures properties of cell polarity.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The Na(+)-HCO(3)(-) cotransporter (NBC) plays a key role in intracellular pH (pH(i)) regulation in normal ventricular muscle. However, the state of NBC in nonischemic hypertrophied hearts is unresolved. In this study, we examined functional and molecular properties of NBC in adult rat ventricular myocytes. The cells were enzymatically isolated from both normal and hypertrophied hearts. Ventricular hypertrophy was induced by pressure overload created by suprarenal abdominal aortic constriction of 50% for 7 wk. pH(i) was measured in single cells using the fluorescent pH indicator 2',7'-bis(2-carboxyethyl)5-(6)carboxyfluorescein. Real-time PCR analysis was used to quantitatively assess expression of NBC-encoding mRNA, including SLC4A4 (encoding electrogenic NBC, NBCe1) and SLC4A7 (electroneutral NBC, NBCn1). Our results demonstrate that: 1) mRNA levels of both the electrogenic NBCe1 (SLC4A4) and electroneutral NBCn1 (SLC4A7) forms of NBC were increased by aortic constriction, 2) the onset of NBC upregulation occurred within 3 days after constriction, 3) normal and hypertrophied ventricles displayed regional differences in NBC expression, 4) acid extrusion via NBC (J(NBC)) was increased significantly in hypertrophied myocytes, 5) although acid extrusion via Na(+)/H(+) exchange was also increased in hypertrophied myocytes, the relative enhancement of J(NBC) was larger, 6) membrane depolarization markedly increased J(NBC) in hypertrophied myocytes, and 7) losartan, an ANG II AT(1) receptor antagonist, significantly attenuated the upregulation of both NBCs induced by 3 wk of aortic constriction. Enhanced NBC activity during hypertrophic development provides a mechanism for intracellular Na(+) overload, which may render the ventricles more vulnerable to Ca(2+) overload during ischemia-reperfusion.", "classifications": [ { "id": "Tanaka", "label": "Group Tanaka", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Taku", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Shirayama", "name": null }, { "creator_type": "author", "first_name": "Tomohiko", "last_name": "Sakatani", "name": null }, { "creator_type": "author", "first_name": "Tomosaburo", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Hideo", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Tetsuro", "last_name": "Takamatsu", "name": null }, { "creator_type": "author", "first_name": "Kenneth W.", "last_name": "Spitzer", "name": null }, { "creator_type": "author", "first_name": "Hiroaki", "last_name": "Matsubara", "name": null } ], "identifiers": { "doi": { "normalized": "10.1152/ajpheart.00964.2006" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "17416604" } }, "mesh": [ { "descriptor": "Angiotensin II Type 1 Receptor Blockers", "descriptor_ui": "D047228", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Aorta, Abdominal", "descriptor_ui": "D001012", "major_topic": false }, { "descriptor": "Disease Models, Animal", "descriptor_ui": "D004195", "major_topic": false }, { "descriptor": "Heart Ventricles", "descriptor_ui": "D006352", "major_topic": false }, { "descriptor": "Hydrogen-Ion Concentration", "descriptor_ui": "D006863", "major_topic": false }, { "descriptor": "Hypertension", "descriptor_ui": "D006973", "major_topic": false }, { "descriptor": "Hypertrophy, Left Ventricular", "descriptor_ui": "D017379", "major_topic": false }, { "descriptor": "Ligation", "descriptor_ui": "D008026", "major_topic": false }, { "descriptor": "Losartan", "descriptor_ui": "D019808", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Membrane Potentials", "descriptor_ui": "D008564", "major_topic": false }, { "descriptor": "Myocytes, Cardiac", "descriptor_ui": "D032383", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Rats, Wistar", "descriptor_ui": "D017208", "major_topic": false }, { "descriptor": "RNA, Messenger", "descriptor_ui": "D012333", "major_topic": false }, { "descriptor": "Sodium-Bicarbonate Symporters", "descriptor_ui": "D027982", "major_topic": false }, { "descriptor": "Sodium-Potassium-Exchanging ATPase", "descriptor_ui": "D000254", "major_topic": false }, { "descriptor": "Time Factors", "descriptor_ui": "D013997", "major_topic": false }, { "descriptor": "Transcription, Genetic", "descriptor_ui": "D014158", "major_topic": true }, { "descriptor": "Up-Regulation", "descriptor_ui": "D015854", "major_topic": false } ], "publication": { "conference_name": null, "date": "2007 Aug", "date_precision": "unknown", "issue": "2", "normalized_date": null, "pages": "H1254-1264", "proceedings_title": null, "publisher": "", "title": "American journal of physiology. Heart and circulatory physiology", "volume": "293", "year": 2007 }, "ssbd": { "database": [], "repository": [] }, "title": "Enhanced activity of ventricular Na+-HCO3- cotransport in pressure overload hypertrophy.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Transforming growth factor-beta (TGF-beta) superfamily members play an important role in growth, differentiation, adhesion, apoptosis, and development in many species from insects and worms to vertebrates. Recently, TGF-beta signaling has been demonstrated to be negatively regulated by microtubules (MTs), which anchor endogenous Smad2/3 to cytosol and also directly interact with connexin43 (Cx43), and the activity of TGF-beta is mediated by Cx43. However, the mechanism underlying the intracellular regulation of TGF-beta activity by Cx43 remains unknown. Here, we found that the functional link between TGF-beta activation and Cx43 is mediated by interactions among Smad2/3, MTs, and Cx43. We confirmed that Cx43 competes with Smad2/3 for binding to MTs, which Cx43 specifically induces release of Smad2/3 from MTs and increases phospho-Smad2 and which, as a result, Smad2/3 and Smad4 are accumulated in the nucleus, leading to activation of the transcription of target genes. Consistently, knockdown of the endogenous Cx43 activity with double-strand RNA (dsRNA) in HL1 cardiomyocytes and Cx43 knockout mice cardiomyocytes consistently show the opposite effect. Our findings demonstrate a novel mechanism for Cx43 positive regulation of TGF-beta function.", "classifications": [ { "id": "Tanaka", "label": "Group Tanaka", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Ping", "last_name": "Dai", "name": null }, { "creator_type": "author", "first_name": "Takuo", "last_name": "Nakagami", "name": null }, { "creator_type": "author", "first_name": "Hideo", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Toshiaki", "last_name": "Hitomi", "name": null }, { "creator_type": "author", "first_name": "Tetsuro", "last_name": "Takamatsu", "name": null } ], "identifiers": { "doi": { "normalized": "10.1091/mbc.e06-12-1064" }, "pmcid": { "normalized": "PMC1877122" }, "pmid": { "normalized": "17429065" } }, "mesh": [ { "descriptor": "Active Transport, Cell Nucleus", "descriptor_ui": "D021581", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Connexin 43", "descriptor_ui": "D018031", "major_topic": false }, { "descriptor": "HeLa Cells", "descriptor_ui": "D006367", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Microtubules", "descriptor_ui": "D008870", "major_topic": false }, { "descriptor": "Protein Binding", "descriptor_ui": "D011485", "major_topic": false }, { "descriptor": "Recombinant Fusion Proteins", "descriptor_ui": "D011993", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Smad2 Protein", "descriptor_ui": "D051899", "major_topic": false }, { "descriptor": "Smad3 Protein", "descriptor_ui": "D051900", "major_topic": false }, { "descriptor": "Transforming Growth Factor beta", "descriptor_ui": "D016212", "major_topic": false }, { "descriptor": "Tubulin", "descriptor_ui": "D014404", "major_topic": false } ], "publication": { "conference_name": null, "date": "2007 Jun", "date_precision": "unknown", "issue": "6", "normalized_date": null, "pages": "2264-2273", "proceedings_title": null, "publisher": "", "title": "Molecular biology of the cell", "volume": "18", "year": 2007 }, "ssbd": { "database": [], "repository": [] }, "title": "Cx43 mediates TGF-beta signaling through competitive Smads binding to microtubules.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Kolliker-Fuse nucleus (KF) neurons are considered to excite motoneurons in the phrenic nucleus (PhN) during inspiration through its projection to the PhN and/or to the rostral ventral respiratory group (rVRG), which in turn projects to the PhN, probably by releasing glutamate from their axon terminals. Using a combined retrograde tracing and in situ hybridization technique, here we demonstrate that most of the KF neurons projecting to the PhN and rVRG contain vesicular glutamate transporter 2 (VGLUT2) mRNA but not glutamic acid decarboxylase 67 (GAD67) mRNA, providing definitive evidence that these neurons are glutamatergic. Together with previous data by Stornetta et al. [Stornetta, R.L., Sevigny, C.P., Guyenet, P.G., 2003b. Inspiratory argumenting bulbospinal neurons express both glutamatergic and enkephalinergic phenotypes. J. Comp. Neurol. 455, 113-124], indicating that PhN-projecting rVRG neurons are VGLUT2 mRNA-positive, the present results suggest that the glutamatergic KF-PhN pathway and/or the glutamatergic KF-rVRG-PhN pathway transmit excitatory outputs of KF neurons to the PhN neurons during inspiration.", "classifications": [ { "id": "Yokota", "label": "Group Yokota", "parent": "Enomoto", "type": "group" }, { "id": "Enomoto", "label": "Team Enomoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Shigefumi", "last_name": "Yokota", "name": null }, { "creator_type": "author", "first_name": "Tatsuro", "last_name": "Oka", "name": null }, { "creator_type": "author", "first_name": "Toshiko", "last_name": "Tsumori", "name": null }, { "creator_type": "author", "first_name": "Sawako", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Yukihiko", "last_name": "Yasui", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.neures.2007.08.004" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "17888537" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Axonal Transport", "descriptor_ui": "D001370", "major_topic": false }, { "descriptor": "gamma-Aminobutyric Acid", "descriptor_ui": "D005680", "major_topic": false }, { "descriptor": "Glutamate Decarboxylase", "descriptor_ui": "D005968", "major_topic": false }, { "descriptor": "Glutamic Acid", "descriptor_ui": "D018698", "major_topic": false }, { "descriptor": "In Situ Hybridization", "descriptor_ui": "D017403", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Medulla Oblongata", "descriptor_ui": "D008526", "major_topic": false }, { "descriptor": "Neural Pathways", "descriptor_ui": "D009434", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Phrenic Nerve", "descriptor_ui": "D010791", "major_topic": false }, { "descriptor": "Pons", "descriptor_ui": "D011149", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Rats, Wistar", "descriptor_ui": "D017208", "major_topic": false }, { "descriptor": "Respiration", "descriptor_ui": "D012119", "major_topic": false }, { "descriptor": "Respiratory Center", "descriptor_ui": "D012125", "major_topic": false }, { "descriptor": "RNA, Messenger", "descriptor_ui": "D012333", "major_topic": false }, { "descriptor": "Staining and Labeling", "descriptor_ui": "D013194", "major_topic": false }, { "descriptor": "Synaptic Transmission", "descriptor_ui": "D009435", "major_topic": false }, { "descriptor": "Vesicular Glutamate Transport Protein 2", "descriptor_ui": "D050599", "major_topic": false } ], "publication": { "conference_name": null, "date": "2007 Nov", "date_precision": "unknown", "issue": "3", "normalized_date": null, "pages": "341-346", "proceedings_title": null, "publisher": "", "title": "Neuroscience research", "volume": "59", "year": 2007 }, "ssbd": { "database": [], "repository": [] }, "title": "Glutamatergic neurons in the Kolliker-Fuse nucleus project to the rostral ventral respiratory group and phrenic nucleus: a combined retrograde tracing and in situ hybridization study in the rat.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "AlkB is an Escherichia coli protein that catalyses the oxidative demethylation of 1-methyladenine and 3-methylcytosine in DNA and RNA. The enzyme activity of AlkB is dependent on a 2-oxoglutarate- and Fe(II)-dependent (2OG-Fe[II]) oxygenase domain. Human AlkB homologues (hABH), hABH1, hABH2 and hABH3, which also possess the 2OG-Fe(II) oxygenase domain, have previously been identified. Recent bioinformatics analysis suggests the existence of an additional five ABH genes in humans. In this study, we identified the hABH4-hABH7 mRNAs and determined their expression in human tissues. Moreover, an hABH2 splice variant lacking the 2OG-Fe(II) oxygenase domain and a new gene, hABH8, were cloned from testis cDNA. hABH8 possesses not only the 2OG-Fe(II) oxygenase domain but both an RNA-binding motif and a methyl-transferase domain. mRNA of the eight hABH molecules was detected in the 16 normal human tissues examined. The sub-cellular localization of EmGFP-hABH8 was restricted to the cytoplasm. EmGFP-hABH1, 3, 4, 6 and 7 were localized in both the cytoplasm and nuclei. Interestingly, the EmGFP-hABH2 splice variant localized in nucleoplasm with a dot-like pattern. In some HeLa cells transfected with EmGFP-hABH5, dot-like fluorescence was also detected in the cytoplasm. These observations provide important information for the future annotation of the hABH family of molecules.", "classifications": [ { "id": "Suzuki", "label": "Group Suzuki", "parent": "Takekawa", "type": "group" }, { "id": "Takekawa", "label": "Team Takekawa", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Kazutake", "last_name": "Tsujikawa", "name": null }, { "creator_type": "author", "first_name": "Kazuhisa", "last_name": "Koike", "name": null }, { "creator_type": "author", "first_name": "Kaori", "last_name": "Kitae", "name": null }, { "creator_type": "author", "first_name": "Aina", "last_name": "Shinkawa", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Arima", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Mutsumi", "last_name": "Tsuchiya", "name": null }, { "creator_type": "author", "first_name": "Yasutaka", "last_name": "Makino", "name": null }, { "creator_type": "author", "first_name": "Tatsuhiko", "last_name": "Furukawa", "name": null }, { "creator_type": "author", "first_name": "Noboru", "last_name": "Konishi", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Yamamoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/j.1582-4934.2007.00094.x" }, "pmcid": { "normalized": "PMC4401260" }, "pmid": { "normalized": "17979886" } }, "mesh": [ { "descriptor": "Amino Acid Sequence", "descriptor_ui": "D000595", "major_topic": false }, { "descriptor": "Base Sequence", "descriptor_ui": "D001483", "major_topic": false }, { "descriptor": "Cloning, Molecular", "descriptor_ui": "D003001", "major_topic": false }, { "descriptor": "DNA Repair Enzymes", "descriptor_ui": "D045643", "major_topic": false }, { "descriptor": "DNA, Complementary", "descriptor_ui": "D018076", "major_topic": false }, { "descriptor": "Gene Expression Profiling", "descriptor_ui": "D020869", "major_topic": true }, { "descriptor": "Gene Expression Regulation, Enzymologic", "descriptor_ui": "D015971", "major_topic": true }, { "descriptor": "Green Fluorescent Proteins", "descriptor_ui": "D049452", "major_topic": false }, { "descriptor": "HeLa Cells", "descriptor_ui": "D006367", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Immunoblotting", "descriptor_ui": "D015151", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Molecular Sequence Data", "descriptor_ui": "D008969", "major_topic": false }, { "descriptor": "Protein Transport", "descriptor_ui": "D021381", "major_topic": false }, { "descriptor": "Recombinant Fusion Proteins", "descriptor_ui": "D011993", "major_topic": false }, { "descriptor": "Reverse Transcriptase Polymerase Chain Reaction", "descriptor_ui": "D020133", "major_topic": false }, { "descriptor": "Subcellular Fractions", "descriptor_ui": "D013347", "major_topic": false }, { "descriptor": "Testis", "descriptor_ui": "D013737", "major_topic": false } ], "publication": { "conference_name": null, "date": "2007 Sep-Oct", "date_precision": "unknown", "issue": "5", "normalized_date": null, "pages": "1105-1116", "proceedings_title": null, "publisher": "", "title": "Journal of cellular and molecular medicine", "volume": "11", "year": 2007 }, "ssbd": { "database": [], "repository": [] }, "title": "Expression and sub-cellular localization of human ABH family molecules.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The pituitary gland is composed of two distinct entities: the adenohypophysis, including the anterior and intermediate lobes, and the neurohypophysis, known as the posterior lobe. This critical endocrine organ is essential for homeostasis, metabolism, reproduction, and growth. The pituitary development requires the control of proliferation and differentiation of progenitor cells. Although multiple signaling molecules and transcription factors are required for the proper pituitary development, the mechanisms that regulate the fate of progenitor cells remain to be elucidated. Hes genes, known as Notch effectors, play a crucial role in specifying cellular fates during the development of various tissues and organs. Here, we report that mice deficient for Hes1 and Hes5 display severe pituitary hypoplasia caused by accelerated differentiation of progenitor cells. In addition, this hypoplastic pituitary gland (adenohypophysis) lacks the intermediate lobe and exhibits the features of the anterior lobe only. Hes1 and Hes5 double-mutant mice also lack the neurohypophysis (the posterior lobe), probably due to incomplete evagination of the diencephalon. Thus, Hes genes control not only maintenance of progenitor cells but also intermediate vs. anterior lobe specification during the adenohypophysis development. Hes genes are also essential for the formation of the neurohypophysis.", "classifications": [ { "id": "Imayoshi", "label": "Group Imayoshi", "parent": "Imayoshi", "type": "group" }, { "id": "Imayoshi", "label": "Team Imayoshi", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Aya", "last_name": "Kita", "name": null }, { "creator_type": "author", "first_name": "Itaru", "last_name": "Imayoshi", "name": null }, { "creator_type": "author", "first_name": "Masato", "last_name": "Hojo", "name": null }, { "creator_type": "author", "first_name": "Masashi", "last_name": "Kitagawa", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Kokubu", "name": null }, { "creator_type": "author", "first_name": "Ryosuke", "last_name": "Ohsawa", "name": null }, { "creator_type": "author", "first_name": "Toshiyuki", "last_name": "Ohtsuka", "name": null }, { "creator_type": "author", "first_name": "Ryoichiro", "last_name": "Kageyama", "name": null }, { "creator_type": "author", "first_name": "Nobuo", "last_name": "Hashimoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1210/me.2007-0039" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "17426285" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Basic Helix-Loop-Helix Proteins", "descriptor_ui": "D051792", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Homeodomain Proteins", "descriptor_ui": "D018398", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Mutant Strains", "descriptor_ui": "D008817", "major_topic": false }, { "descriptor": "Organogenesis", "descriptor_ui": "D038081", "major_topic": false }, { "descriptor": "Pituitary Gland, Posterior", "descriptor_ui": "D010904", "major_topic": false }, { "descriptor": "Repressor Proteins", "descriptor_ui": "D012097", "major_topic": false }, { "descriptor": "Stem Cells", "descriptor_ui": "D013234", "major_topic": false }, { "descriptor": "Transcription Factor HES-1", "descriptor_ui": "D000072056", "major_topic": false } ], "publication": { "conference_name": null, "date": "2007 Jun", "date_precision": "unknown", "issue": "6", "normalized_date": null, "pages": "1458-1466", "proceedings_title": null, "publisher": "", "title": "Molecular endocrinology (Baltimore, Md.)", "volume": "21", "year": 2007 }, "ssbd": { "database": [], "repository": [] }, "title": "Hes1 and Hes5 control the progenitor pool, intermediate lobe specification, and posterior lobe formation in the pituitary development.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The organization of projections from the central amygdaloid nucleus (CeA) to the paraventricuilar hypothalamic nucleus (PVH) has been studied in order to understand the anatomical substrates of amygdaloid modulation of endocrine and autonomic functions, and a hypothesis that the bed nucleus of the stria terminalis (BST) may act as a relay site between the CeA and PVH has been proposed. Using anterograde and retrograde tract-tracing methods, in the rat, we first indicated that neurons in the parastrial nucleus (PS), where projection fibers from the central amygdaloid nucleus (CeA) terminated, sent their axons to the paraventricular hypothalamic nucleus (PVH). We further demonstrated that the CeA terminals formed symmetrical synaptic contacts with somata and dendrites of the PVH-projecting PS neurons, and that the PS received CeA fibers predominantly from the lateral part and sent large numbers of projection fibers to almost all the subdivisions of the PVH. Using anterograde tracing combined with the postembedding immunogold method, we finally revealed that nearly all the CeA terminals in the PS were immunoreactive for gamma-aminobutyric acid. The present data suggest that output signals from the CeA are transmitted disynaptically to the PVH neurons via the PS neurons and modulate PVH neuron activity by way of disinhibition.", "classifications": [ { "id": "Yokota", "label": "Group Yokota", "parent": "Enomoto", "type": "group" }, { "id": "Enomoto", "label": "Team Enomoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Ken", "last_name": "Tsubouchi", "name": null }, { "creator_type": "author", "first_name": "Toshiko", "last_name": "Tsumori", "name": null }, { "creator_type": "author", "first_name": "Shigefumi", "last_name": "Yokota", "name": null }, { "creator_type": "author", "first_name": "Hideki", "last_name": "Okunishi", "name": null }, { "creator_type": "author", "first_name": "Yukihiko", "last_name": "Yasui", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.neures.2007.08.010" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "17897744" } }, "mesh": [ { "descriptor": "Amygdala", "descriptor_ui": "D000679", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Axonal Transport", "descriptor_ui": "D001370", "major_topic": false }, { "descriptor": "Biotin", "descriptor_ui": "D001710", "major_topic": false }, { "descriptor": "Brain Mapping", "descriptor_ui": "D001931", "major_topic": false }, { "descriptor": "Cholera Toxin", "descriptor_ui": "D002772", "major_topic": false }, { "descriptor": "Dendrites", "descriptor_ui": "D003712", "major_topic": false }, { "descriptor": "Dextrans", "descriptor_ui": "D003911", "major_topic": false }, { "descriptor": "gamma-Aminobutyric Acid", "descriptor_ui": "D005680", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Microscopy, Immunoelectron", "descriptor_ui": "D016253", "major_topic": false }, { "descriptor": "Neural Inhibition", "descriptor_ui": "D009433", "major_topic": false }, { "descriptor": "Neural Pathways", "descriptor_ui": "D009434", "major_topic": false }, { "descriptor": "Paraventricular Hypothalamic Nucleus", "descriptor_ui": "D010286", "major_topic": false }, { "descriptor": "Presynaptic Terminals", "descriptor_ui": "D017729", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Rats, Wistar", "descriptor_ui": "D017208", "major_topic": false }, { "descriptor": "Septal Nuclei", "descriptor_ui": "D012686", "major_topic": false }, { "descriptor": "Synapses", "descriptor_ui": "D013569", "major_topic": false } ], "publication": { "conference_name": null, "date": "2007 Dec", "date_precision": "unknown", "issue": "4", "normalized_date": null, "pages": "390-398", "proceedings_title": null, "publisher": "", "title": "Neuroscience research", "volume": "59", "year": 2007 }, "ssbd": { "database": [], "repository": [] }, "title": "A disynaptic pathway from the central amygdaloid nucleus to the paraventricular hypothalamic nucleus via the parastrial nucleus in the rat.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "", "classifications": [ { "id": "Sodeoka", "label": "Group Sodeoka", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Go", "last_name": "Hirai", "name": null }, { "creator_type": "author", "first_name": "Tadashi", "last_name": "Shimizu", "name": null }, { "creator_type": "author", "first_name": "Toru", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Yosuke", "last_name": "Ogoshi", "name": null }, { "creator_type": "author", "first_name": "Megumi", "last_name": "Ohkubo", "name": null }, { "creator_type": "author", "first_name": "Mikiko", "last_name": "Sodeoka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/cmdc.200700080" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "17492704" } }, "mesh": [ { "descriptor": "Enzyme Activation", "descriptor_ui": "D004789", "major_topic": false }, { "descriptor": "Furans", "descriptor_ui": "D005663", "major_topic": false }, { "descriptor": "Hydrogen Bonding", "descriptor_ui": "D006860", "major_topic": false }, { "descriptor": "Ligands", "descriptor_ui": "D008024", "major_topic": false }, { "descriptor": "Models, Molecular", "descriptor_ui": "D008958", "major_topic": false }, { "descriptor": "Protein Kinase C-alpha", "descriptor_ui": "D051571", "major_topic": false }, { "descriptor": "Structure-Activity Relationship", "descriptor_ui": "D013329", "major_topic": false } ], "publication": { "conference_name": null, "date": "2007 Jul", "date_precision": "unknown", "issue": "7", "normalized_date": null, "pages": "1006-1009", "proceedings_title": null, "publisher": "", "title": "ChemMedChem", "volume": "2", "year": 2007 }, "ssbd": { "database": [], "repository": [] }, "title": "Importance of interaction between C1 domain and lipids in protein kinase C alpha activation: hydrophobic side chain direction in isobenzofuranone ligands controls enzyme activation level.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The mitogen-activated protein kinase (MAPK) module, composed of a MAPK, a MAPK kinase (MAPKK), and a MAPKK kinase (MAPKKK), is a cellular signaling device that is conserved throughout the eukaryotic world. In mammalian cells, various extracellular stresses activate two major subfamilies of MAPKs, namely, the Jun N-terminal kinases and the p38/stress-activated MAPK (SAPK). MTK1 (also called MEKK4) is a stress-responsive MAPKKK that is bound to and activated by the stress-inducible GADD45 family of proteins (GADD45α/β/γ). Here, we dissected the molecular mechanism of MTK1 activation by GADD45 proteins. The MTK1 N terminus bound to its C-terminal segment, thereby inhibiting the C-terminal kinase domain. This N-C interaction was disrupted by the binding of GADD45 to the MTK1 N-terminal GADD45-binding site. GADD45 binding also induced MTK1 dimerization via a dimerization domain containing a coiled-coil motif, which is essential for the trans autophosphorylation of MTK1 at Thr-1493 in the kinase activation loop. An MTK1 alanine substitution mutant at Thr-1493 has a severely reduced activity. Thus, we conclude that GADD45 binding induces MTK1 N-C dissociation, dimerization, and autophosphorylation at Thr-1493, leading to the activation of the kinase catalytic domain. Constitutively active MTK1 mutants induced the same events, but in the absence of GADD45.", "classifications": [ { "id": "Takekawa", "label": "Group Takekawa", "parent": "Takekawa", "type": "group" }, { "id": "Takekawa", "label": "Team Takekawa", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Zenshi", "last_name": "Miyake", "name": null }, { "creator_type": "author", "first_name": "Mutsuhiro", "last_name": "Takekawa", "name": null }, { "creator_type": "author", "first_name": "Qingyuan", "last_name": "Ge", "name": null }, { "creator_type": "author", "first_name": "Haruo", "last_name": "Saito", "name": null } ], "identifiers": { "doi": { "normalized": "10.1128/mcb.01435-06" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "17242196" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Chlorocebus aethiops", "descriptor_ui": "D002522", "major_topic": false }, { "descriptor": "COS Cells", "descriptor_ui": "D019556", "major_topic": false }, { "descriptor": "Dimerization", "descriptor_ui": "D019281", "major_topic": false }, { "descriptor": "Enzyme Activation", "descriptor_ui": "D004789", "major_topic": false }, { "descriptor": "GADD45 Proteins", "descriptor_ui": "D000097642", "major_topic": false }, { "descriptor": "Intracellular Signaling Peptides and Proteins", "descriptor_ui": "D047908", "major_topic": false }, { "descriptor": "MAP Kinase Kinase Kinase 4", "descriptor_ui": "D048768", "major_topic": false }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": false }, { "descriptor": "Phosphorylation", "descriptor_ui": "D010766", "major_topic": false }, { "descriptor": "Protein Binding", "descriptor_ui": "D011485", "major_topic": false }, { "descriptor": "Protein Structure, Tertiary", "descriptor_ui": "D017434", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Tyrosine", "descriptor_ui": "D014443", "major_topic": false } ], "publication": { "conference_name": null, "date": "2007 Apr", "date_precision": "unknown", "issue": "7", "normalized_date": null, "pages": "2765-2776", "proceedings_title": null, "publisher": "", "title": "Molecular and Cellular Biology", "volume": "27", "year": 2007 }, "ssbd": { "database": [], "repository": [] }, "title": "Activation of MTK1/MEKK4 by GADD45 through Induced N-C Dissociation and Dimerization-Mediated trans Autophosphorylation of the MTK1 Kinase Domain▿†.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Recent discovery of mutations in the tyrosine kinase domain of the epidermal growth factor receptor (EGFR) gene in lung adenocarcinoma greatly stimulated biomarker research on predictive factors for EGFR tyrosine kinase inhibitors (TKI), such as gefitinib and erlotinib. Although patients with activating mutations of the EGFR generally respond to EGFR TKIs very well, it is natural to assume that there is no sole determinant, considering great complexity and redundancy of the EGFR pathway. Subsequently, roles of different types of EGFR mutations or mutations of genes that are members of the EGFR pathway such as KRAS and HER2 have been evaluated. In this review, we summarize the recent findings about how mutations of the EGFR and related genes affect sensitivity to EFGR-TKIs. We also discuss molecular mechanisms of acquired resistance to EGFR-TKIs that is almost inevitable in EGFR-TKI therapy. The door for genotype-based treatment of lung cancer is beginning to open, and through these efforts, it will be possible to slow the progression of lung cancer and eventually, to decrease mortality from lung cancer.", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Tetsuya", "last_name": "Mitsudomi", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/j.1349-7006.2007.00607.x" }, "pmcid": { "normalized": "PMC11159145" }, "pmid": { "normalized": "17888036" } }, "mesh": [ { "descriptor": "Antineoplastic Agents", "descriptor_ui": "D000970", "major_topic": false }, { "descriptor": "Enzyme Inhibitors", "descriptor_ui": "D004791", "major_topic": false }, { "descriptor": "ErbB Receptors", "descriptor_ui": "D066246", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Lung Neoplasms", "descriptor_ui": "D008175", "major_topic": false }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": true }, { "descriptor": "Protein-Tyrosine Kinases", "descriptor_ui": "D011505", "major_topic": false } ], "publication": { "conference_name": null, "date": "2007 Dec", "date_precision": "unknown", "issue": "12", "normalized_date": null, "pages": "1817-1824", "proceedings_title": null, "publisher": "", "title": "Cancer science", "volume": "98", "year": 2007 }, "ssbd": { "database": [], "repository": [] }, "title": "Mutations of the epidermal growth factor receptor gene and related genes as determinants of epidermal growth factor receptor tyrosine kinase inhibitors sensitivity in lung cancer.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Neurons develop distinctive dendritic morphologies to receive and process information. Previous experiments showed that competitive dendro-dendritic interactions play critical roles in shaping dendrites of the space-filling type, which uniformly cover their receptive field. We incorporated this finding in constructing a new mathematical model, in which reaction dynamics of two chemicals (activator and suppressor) are coupled to neuronal dendrite growth. Our numerical analysis determined the conditions for dendritic branching and suggested that the self-organizing property of the proposed system can underlie dendritogenesis. Furthermore, we found a clear correlation between dendrite shape and the distribution of the activator, thus providing a morphological criterion to predict the in vivo distribution of the hypothetical molecular complexes responsible for dendrite elongation and branching.", "classifications": [ { "id": "Mochizuki", "label": "Group Mochizuki", "parent": "Eiraku", "type": "group" }, { "id": "Eiraku", "label": "Team Eiraku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Kaoru", "last_name": "Sugimura", "name": null }, { "creator_type": "author", "first_name": "Kohei", "last_name": "Shimono", "name": null }, { "creator_type": "author", "first_name": "Tadashi", "last_name": "Uemura", "name": null }, { "creator_type": "author", "first_name": "Atsushi", "last_name": "Mochizuki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1371/journal.pcbi.0030212" }, "pmcid": { "normalized": "PMC2077899" }, "pmid": { "normalized": "18020700" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Communication", "descriptor_ui": "D002450", "major_topic": false }, { "descriptor": "Cell Enlargement", "descriptor_ui": "D049108", "major_topic": false }, { "descriptor": "Cell Proliferation", "descriptor_ui": "D049109", "major_topic": false }, { "descriptor": "Cell Size", "descriptor_ui": "D048429", "major_topic": false }, { "descriptor": "Computer Simulation", "descriptor_ui": "D003198", "major_topic": false }, { "descriptor": "Dendrites", "descriptor_ui": "D003712", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Models, Biological", "descriptor_ui": "D008954", "major_topic": true }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false } ], "publication": { "conference_name": null, "date": "2007 Nov", "date_precision": "unknown", "issue": "11", "normalized_date": null, "pages": "e212", "proceedings_title": null, "publisher": "", "title": "PLoS computational biology", "volume": "3", "year": 2007 }, "ssbd": { "database": [], "repository": [] }, "title": "Self-organizing mechanism for development of space-filling neuronal dendrites.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The orientation of mitotic spindles, which determines the plane of cell division, is tightly regulated in polarized cells such as epithelial cells, but it has been unclear whether there is a mechanism regulating spindle orientation in non-polarized cultured cells. In adherent cultured cells, spindles are positioned at the center of the cells and the axis of the spindle lies in the longest axis of the cell. Thus, cell geometry is thought to be one of cues for spindle orientation and positioning in cultured cells because this defines the center and the long axis of the cell. Recent work provides a new insight into the spindle orientation in cultured cells; spindles are aligned along the axis parallel to the cell-substrate adhesion plane. Concomitantly, integrin-mediated cell adhesion to the extracellular matrix (ECM), rather than gravitation, cell-cell adhesion or cell geometry, has shown to be essential for this mechanism of spindle orientation. Several independent lines of evidence confirm the involvement of cell-ECM adhesion in spindle orientation in both cultured cells and in developing organisms. The important future challenge is to identify a molecular mechanism(s) that links integrin and spindles in the control of spindle axis.", "classifications": [ { "id": "Toyoshima", "label": "Group Toyoshima", "parent": "Toyoshima", "type": "group" }, { "id": "Toyoshima", "label": "Team Toyoshima", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Fumiko", "last_name": "Toyoshima", "name": null }, { "creator_type": "author", "first_name": "Eisuke", "last_name": "Nishida", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/jcp.21227" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "17654475" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Polarity", "descriptor_ui": "D016764", "major_topic": false }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Extracellular Matrix", "descriptor_ui": "D005109", "major_topic": false }, { "descriptor": "Integrins", "descriptor_ui": "D016023", "major_topic": false }, { "descriptor": "Mitosis", "descriptor_ui": "D008938", "major_topic": false }, { "descriptor": "Spindle Apparatus", "descriptor_ui": "D008941", "major_topic": true } ], "publication": { "conference_name": null, "date": "2007 Nov", "date_precision": "unknown", "issue": "2", "normalized_date": null, "pages": "407-411", "proceedings_title": null, "publisher": "", "title": "Journal of cellular physiology", "volume": "213", "year": 2007 }, "ssbd": { "database": [], "repository": [] }, "title": "Spindle orientation in animal cell mitosis: roles of integrin in the control of spindle axis.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: With the advent of metabolomics as a powerful tool for both functional and biomarker discovery, the identification of specific differences between complex metabolite profiles is becoming a major challenge in the data analysis pipeline. The task remains difficult, given the datasets' size, complexity, and common shifts in migration (elution/retention) times between samples analyzed by hyphenated mass spectrometry methods. RESULTS: We present a Mathematica (Wolfram Research, Inc.) package MathDAMP (Mathematica package for Differential Analysis of Metabolite Profiles), which highlights differences between raw datasets acquired by hyphenated mass spectrometry methods by applying arithmetic operations to all corresponding signal intensities on a datapoint-by-datapoint basis. Peak identification and integration is thus bypassed and the results are displayed graphically. To facilitate direct comparisons, the raw datasets are automatically preprocessed and normalized in terms of both migration times and signal intensities. A combination of dynamic programming and global optimization is used for the alignment of the datasets along the migration time dimension. The processed datasets and the results of direct comparisons between them are visualized using density plots (axes represent migration time and m/z values while peaks appear as color-coded spots) providing an intuitive overall view. Various forms of comparisons and statistical tests can be applied to highlight subtle differences. Overlaid electropherograms (chromatograms) corresponding to the vicinities of the candidate differences from any result may be generated in a descending order of significance for visual confirmation. Additionally, a standard library table (a list of m/z values and migration times for known compounds) may be aligned and overlaid on the plots to allow easier identification of metabolites. CONCLUSION: Our tool facilitates the visualization and identification of differences between complex metabolite profiles according to various criteria in an automated fashion and is useful for data-driven discovery of biomarkers and functional genomics.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Richard", "last_name": "Baran", "name": null }, { "creator_type": "author", "first_name": "Hayataro", "last_name": "Kochi", "name": null }, { "creator_type": "author", "first_name": "Natsumi", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Suematsu", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Takaaki", "last_name": "Nishioka", "name": null }, { "creator_type": "author", "first_name": "Martin", "last_name": "Robert", "name": null }, { "creator_type": "author", "first_name": "Masaru", "last_name": "Tomita", "name": null } ], "identifiers": { "doi": { "normalized": "10.1186/1471-2105-7-530" }, "pmcid": { "normalized": "PMC1764210" }, "pmid": { "normalized": "17166258" } }, "mesh": [ { "descriptor": "Biomarkers", "descriptor_ui": "D015415", "major_topic": false }, { "descriptor": "Computational Biology", "descriptor_ui": "D019295", "major_topic": false }, { "descriptor": "Energy Metabolism", "descriptor_ui": "D004734", "major_topic": true }, { "descriptor": "Mathematical Computing", "descriptor_ui": "D008432", "major_topic": true } ], "publication": { "conference_name": null, "date": "2006 Dec 13", "date_precision": "day", "issue": "", "normalized_date": "2006-12-13", "pages": "530", "proceedings_title": null, "publisher": "", "title": "BMC bioinformatics", "volume": "7", "year": 2006 }, "ssbd": { "database": [], "repository": [] }, "title": "MathDAMP: a package for differential analysis of metabolite profiles.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "KAP1 recruits many proteins involved in gene silencing and functions as an integral part of co-repressor complex. KAP1 was identified as Mdm2-binding protein and shown to form a complex with Mdm2 and p53 in vivo. We examined the role of KAP1 in p53 activation after the treatment of cells with different types of external stresses. KAP1 reduction markedly enhanced the induction of p21, a product of the p53 target gene, after treatment with actinomycin D or gamma-irradiation, but not with camptothecin. Treatment with actinomycin D, but not with camptothecin, augmented the interaction of p53 with Mdm2 and KAP1. Further, KAP1 reduction in actinomycin D-treated cells facilitated cell cycle arrest and negatively affected clonal cell growth. Thus, the reduction of KAP1 levels promotes p53-dependent p21 induction and inhibits cell proliferation in actinomycin D-treated cells. KAP1 may serve as a therapeutic target against cancer in combination with actinomycin D.", "classifications": [ { "id": "Okamoto", "label": "Group Okamoto", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Koji", "last_name": "Okamoto", "name": null }, { "creator_type": "author", "first_name": "Issay", "last_name": "Kitabayashi", "name": null }, { "creator_type": "author", "first_name": "Yoichi", "last_name": "Taya", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.bbrc.2006.10.022" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "17056014" } }, "mesh": [ { "descriptor": "Antineoplastic Agents", "descriptor_ui": "D000970", "major_topic": false }, { "descriptor": "Camptothecin", "descriptor_ui": "D002166", "major_topic": false }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Cell Proliferation", "descriptor_ui": "D049109", "major_topic": false }, { "descriptor": "Cell Survival", "descriptor_ui": "D002470", "major_topic": false }, { "descriptor": "Dactinomycin", "descriptor_ui": "D003609", "major_topic": false }, { "descriptor": "DNA-Binding Proteins", "descriptor_ui": "D004268", "major_topic": false }, { "descriptor": "Dose-Response Relationship, Drug", "descriptor_ui": "D004305", "major_topic": false }, { "descriptor": "Drug Combinations", "descriptor_ui": "D004338", "major_topic": false }, { "descriptor": "Gamma Rays", "descriptor_ui": "D005720", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Neoplasms", "descriptor_ui": "D009369", "major_topic": false }, { "descriptor": "Proto-Oncogene Proteins c-mdm2", "descriptor_ui": "D051736", "major_topic": false }, { "descriptor": "Repressor Proteins", "descriptor_ui": "D012097", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Tripartite Motif-Containing Protein 28", "descriptor_ui": "D000076183", "major_topic": false }, { "descriptor": "Tumor Suppressor Protein p53", "descriptor_ui": "D016159", "major_topic": false } ], "publication": { "conference_name": null, "date": "2006 Dec 8", "date_precision": "day", "issue": "1", "normalized_date": "2006-12-08", "pages": "216-222", "proceedings_title": null, "publisher": "", "title": "Biochemical and biophysical research communications", "volume": "351", "year": 2006 }, "ssbd": { "database": [], "repository": [] }, "title": "KAP1 dictates p53 response induced by chemotherapeutic agents via Mdm2 interaction.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Inhibition of NF-κB activation increases susceptibility to tumor necrosis factor (TNF)α-induced cell death, concurrent with caspases and prolonged c-Jun N-terminal kinase (JNK) activation, and reactive oxygen species (ROS) accumulation. However, the detailed mechanisms are unclear. Here we show that cellular FLICE-inhibitory protein (c-FLIP) is rapidly lost in NF-κB activation-deficient, but not wild-type fibroblasts upon TNFα stimulation, indicating that NF-κB normally maintains the cellular levels of c-FLIP. The ectopic expression of the long form of c-FLIP (c-FLIPL) inhibits TNFα-induced prolonged JNK activation and ROS accumulation in NF-κB activation-deficient fibroblasts. Conversely, TNFα induces prolonged JNK activation and ROS accumulation in c-Flip−/− fibroblasts. Moreover, c-FLIPL directly interacts with a JNK activator, MAP kinase kinase (MKK)7, in a TNFα-dependent manner and inhibits the interactions of MKK7 with MAP/ERK kinase kinase 1, apoptosis-signal-regulating kinase 1, and TGFβ-activated kinase 1. This stimuli-dependent interaction of c-FLIPL with MKK7 might selectively suppress the prolonged phase of JNK activation. Taken that ROS promote JNK activation and activation of the JNK pathway may promote ROS accumulation, c-FLIPL might block this positive feedback loop, thereby suppressing ROS accumulation.", "classifications": [ { "id": "Takekawa", "label": "Group Takekawa", "parent": "Takekawa", "type": "group" }, { "id": "Takekawa", "label": "Team Takekawa", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Akihito", "last_name": "Nakajima", "name": null }, { "creator_type": "author", "first_name": "Sachiko", "last_name": "Komazawa-Sakon", "name": null }, { "creator_type": "author", "first_name": "Mutsuhiro", "last_name": "Takekawa", "name": null }, { "creator_type": "author", "first_name": "Tomonari", "last_name": "Sasazuki", "name": null }, { "creator_type": "author", "first_name": "Wen-Chen", "last_name": "Yeh", "name": null }, { "creator_type": "author", "first_name": "Hideo", "last_name": "Yagita", "name": null }, { "creator_type": "author", "first_name": "Ko", "last_name": "Okumura", "name": null }, { "creator_type": "author", "first_name": "Hiroyasu", "last_name": "Nakano", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/sj.emboj.7601423" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "17110930" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Apoptosis", "descriptor_ui": "D017209", "major_topic": true }, { "descriptor": "CASP8 and FADD-Like Apoptosis Regulating Protein", "descriptor_ui": "D053446", "major_topic": false }, { "descriptor": "Caspases", "descriptor_ui": "D020169", "major_topic": false }, { "descriptor": "Fibroblasts", "descriptor_ui": "D005347", "major_topic": false }, { "descriptor": "Gene Expression Regulation, Enzymologic", "descriptor_ui": "D015971", "major_topic": false }, { "descriptor": "JNK Mitogen-Activated Protein Kinases", "descriptor_ui": "D048031", "major_topic": false }, { "descriptor": "MAP Kinase Kinase 1", "descriptor_ui": "D048369", "major_topic": false }, { "descriptor": "MAP Kinase Kinase 7", "descriptor_ui": "D048688", "major_topic": false }, { "descriptor": "MAP Kinase Kinase Kinase 1", "descriptor_ui": "D048728", "major_topic": false }, { "descriptor": "MAP Kinase Kinase Kinase 5", "descriptor_ui": "D048848", "major_topic": false }, { "descriptor": "MAP Kinase Kinase Kinase 7", "descriptor_ui": "D000099151", "major_topic": false }, { "descriptor": "MAP Kinase Kinase Kinases", "descriptor_ui": "D020930", "major_topic": false }, { "descriptor": "NF-kappa B", "descriptor_ui": "D016328", "major_topic": false }, { "descriptor": "Protein Interaction Mapping", "descriptor_ui": "D025941", "major_topic": false }, { "descriptor": "Protein Structure, Tertiary", "descriptor_ui": "D017434", "major_topic": false }, { "descriptor": "Reactive Oxygen Species", "descriptor_ui": "D017382", "major_topic": false }, { "descriptor": "Superoxide Dismutase", "descriptor_ui": "D013482", "major_topic": false }, { "descriptor": "Tumor Necrosis Factor-alpha", "descriptor_ui": "D014409", "major_topic": false } ], "publication": { "conference_name": null, "date": "2006 Nov 29", "date_precision": "day", "issue": "23", "normalized_date": "2006-11-29", "pages": "5549-5559", "proceedings_title": null, "publisher": "", "title": "The EMBO Journal", "volume": "25", "year": 2006 }, "ssbd": { "database": [], "repository": [] }, "title": "An antiapoptotic protein, c-FLIPL, directly binds to MKK7 and inhibits the JNK pathway.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "We quantitatively examined the possible damage to the growth and cell division ability of Escherichia coli caused by 1064-nm optical trapping. Using the synchronous behavior of two sister E. coli cells, the growth and interdivision times between those two cells, one of which was trapped by optical tweezers, the other was not irradiated, were compared using an on-chip single cell cultivation system. Cell growth stopped during the optical trapping period, even with the smallest irradiated power on the trapped cells. Moreover, the damage to the cell's growth and interdivision period was proportional to the total irradiated energy (work) on the cell, i.e., irradiation time multiplied by irradiation power. The division ability was more easily affected by a smaller energy, 0.36 J, which was 30% smaller than the energy that adversely affected growth, 0.54 J. The results indicate that the damage caused by optical trapping can be estimated from the total energy applied to cells, and furthermore, that the use of optical trapping for manipulating cells might cause damage to cell division and growth mechanisms, even at wavelengths under 1064 nm, if the total irradiation energy is excessive.", "classifications": [ { "id": "Wakamoto", "label": "Group Wakamoto", "parent": "Wakamoto", "type": "group" }, { "id": "Wakamoto", "label": "Team Wakamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Satoru", "last_name": "Ayano", "name": null }, { "creator_type": "author", "first_name": "Yuichi", "last_name": "Wakamoto", "name": null }, { "creator_type": "author", "first_name": "Shinobu", "last_name": "Yamashita", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Yasuda", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.bbrc.2006.09.115" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "17027921" } }, "mesh": [ { "descriptor": "Cell Culture Techniques", "descriptor_ui": "D018929", "major_topic": false }, { "descriptor": "Cell Separation", "descriptor_ui": "D002469", "major_topic": false }, { "descriptor": "Equipment Design", "descriptor_ui": "D004867", "major_topic": false }, { "descriptor": "Equipment Failure Analysis", "descriptor_ui": "D019544", "major_topic": false }, { "descriptor": "Escherichia coli", "descriptor_ui": "D004926", "major_topic": false }, { "descriptor": "Lasers", "descriptor_ui": "D007834", "major_topic": true }, { "descriptor": "Microfluidic Analytical Techniques", "descriptor_ui": "D046210", "major_topic": false }, { "descriptor": "Specimen Handling", "descriptor_ui": "D013048", "major_topic": false } ], "publication": { "conference_name": null, "date": "2006 Nov 24", "date_precision": "day", "issue": "3", "normalized_date": "2006-11-24", "pages": "678-684", "proceedings_title": null, "publisher": "", "title": "Biochemical and biophysical research communications", "volume": "350", "year": 2006 }, "ssbd": { "database": [], "repository": [] }, "title": "Quantitative measurement of damage caused by 1064-nm wavelength optical trapping of Escherichia coli cells using on-chip single cell cultivation system.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Angiotensin (Ang) II participates in the pathogenesis of heart failure through induction of cardiac hypertrophy. Ang II-induced hypertrophic growth of cardiomyocytes is mediated by nuclear factor of activated T cells (NFAT), a Ca(2+)-responsive transcriptional factor. It is believed that phospholipase C (PLC)-mediated production of inositol-1,4,5-trisphosphate (IP(3)) is responsible for Ca(2+) increase that is necessary for NFAT activation. However, we demonstrate that PLC-mediated production of diacylglycerol (DAG) but not IP(3) is essential for Ang II-induced NFAT activation in rat cardiac myocytes. NFAT activation and hypertrophic responses by Ang II stimulation required the enhanced frequency of Ca(2+) oscillation triggered by membrane depolarization through activation of DAG-sensitive TRPC channels, which leads to activation of L-type Ca(2+) channel. Patch clamp recordings from single myocytes revealed that Ang II activated DAG-sensitive TRPC-like currents. Among DAG-activating TRPC channels (TRPC3, TRPC6, and TRPC7), the activities of TRPC3 and TRPC6 channels correlated with Ang II-induced NFAT activation and hypertrophic responses. These data suggest that DAG-induced Ca(2+) signaling pathway through TRPC3 and TRPC6 is essential for Ang II-induced NFAT activation and cardiac hypertrophy.", "classifications": [ { "id": "Nishida", "label": "Group Nishida", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Naoya", "last_name": "Onohara", "name": null }, { "creator_type": "author", "first_name": "Motohiro", "last_name": "Nishida", "name": null }, { "creator_type": "author", "first_name": "Ryuji", "last_name": "Inoue", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Hideki", "last_name": "Sumimoto", "name": null }, { "creator_type": "author", "first_name": "Yoji", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Yasuo", "last_name": "Mori", "name": null }, { "creator_type": "author", "first_name": "Taku", "last_name": "Nagao", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Kurose", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/sj.emboj.7601417" }, "pmcid": { "normalized": "PMC1636614" }, "pmid": { "normalized": "17082763" } }, "mesh": [ { "descriptor": "Angiotensin II", "descriptor_ui": "D000804", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Animals, Newborn", "descriptor_ui": "D000831", "major_topic": false }, { "descriptor": "Calcium Channels, L-Type", "descriptor_ui": "D020746", "major_topic": false }, { "descriptor": "Calcium Signaling", "descriptor_ui": "D020013", "major_topic": false }, { "descriptor": "Cardiomegaly", "descriptor_ui": "D006332", "major_topic": false }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Diglycerides", "descriptor_ui": "D004075", "major_topic": false }, { "descriptor": "Inositol 1,4,5-Trisphosphate", "descriptor_ui": "D015544", "major_topic": false }, { "descriptor": "Ion Channel Gating", "descriptor_ui": "D015640", "major_topic": false }, { "descriptor": "Membrane Potentials", "descriptor_ui": "D008564", "major_topic": false }, { "descriptor": "Myocytes, Cardiac", "descriptor_ui": "D032383", "major_topic": false }, { "descriptor": "NFATC Transcription Factors", "descriptor_ui": "D050778", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "TRPC Cation Channels", "descriptor_ui": "D050052", "major_topic": false }, { "descriptor": "Type C Phospholipases", "descriptor_ui": "D010738", "major_topic": false }, { "descriptor": "Vasoconstrictor Agents", "descriptor_ui": "D014662", "major_topic": false } ], "publication": { "conference_name": null, "date": "2006 Nov 15", "date_precision": "day", "issue": "22", "normalized_date": "2006-11-15", "pages": "5305-5316", "proceedings_title": null, "publisher": "", "title": "The EMBO journal", "volume": "25", "year": 2006 }, "ssbd": { "database": [], "repository": [] }, "title": "TRPC3 and TRPC6 are essential for angiotensin II-induced cardiac hypertrophy.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Cell-to-cell communication is considered to underlie the coordinated behavior and the multicellularity of cell group class, which cannot be explained only by the knowledge of lower class of life system from molecule to individual cell, because they are determined by at least two different ways: diffusible chemical signals and their direct physical contacts. We show in this paper a new method of individual-cell-based cell observation that can estimate the role of cell-to-cell communication, diffusible chemical signals, and physical contacts as separated properties, by applying an on-chip individual-cell-based cultivation system. The exchange of stationary phase medium on isolated individual Escherichia coli from exponential phase medium and the control of physical contacts indicated that the cell-to-cell direct contact did not affect the growth rate; only the communication through diffusible signals affects the growth rates as Hill's equation manner.", "classifications": [ { "id": "Wakamoto", "label": "Group Wakamoto", "parent": "Wakamoto", "type": "group" }, { "id": "Wakamoto", "label": "Team Wakamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yuichi", "last_name": "Wakamoto", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Yasuda", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.bbrc.2006.08.149" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "16970916" } }, "mesh": [ { "descriptor": "Cell Communication", "descriptor_ui": "D002450", "major_topic": true }, { "descriptor": "Cell Proliferation", "descriptor_ui": "D049109", "major_topic": false }, { "descriptor": "Culture Media", "descriptor_ui": "D003470", "major_topic": false }, { "descriptor": "Escherichia coli", "descriptor_ui": "D004926", "major_topic": false }, { "descriptor": "Indicator Dilution Techniques", "descriptor_ui": "D007201", "major_topic": false }, { "descriptor": "Microchip Analytical Procedures", "descriptor_ui": "D046208", "major_topic": false } ], "publication": { "conference_name": null, "date": "2006 Oct 27", "date_precision": "day", "issue": "3", "normalized_date": "2006-10-27", "pages": "1130-1138", "proceedings_title": null, "publisher": "", "title": "Biochemical and biophysical research communications", "volume": "349", "year": 2006 }, "ssbd": { "database": [], "repository": [] }, "title": "Quantitative evaluation of cell-to-cell communication effects in cell group class using on-chip individual-cell-based cultivation system.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Clathrin is a major component of clathrin-coated pits and serves as a binding scaffold for endocytic machinery through the binding of a specific sequence known as the clathrin-binding motif. This motif is also found in cellular signaling proteins other than endocytic components, including G protein-coupled receptor kinase 2 (GRK2), which phosphorylates G protein-coupled receptors and promotes uncoupling of receptor-G protein interaction. However, the functions of clathrin in the regulation of GRK2 are unknown. Here we demonstrated that overexpression of GRK2 mutated at the clathrin-binding motif with alanine (GRK2-5A) results in inhibition of phosphorylation and internalization of the beta2-adrenergic receptor (beta2AR). However, the interaction of beta2AR with GRK2-5A is the same as that of wild type GRK2 as determined by bioluminescence resonance energy transfer. Furthermore, GRK2-5A phosphorylates rhodopsin essentially to the same extent as wild type GRK2 in vitro. Depletion of the clathrin heavy chain using small interference RNA inhibits agonist-induced phosphorylation and internalization of beta2AR. Thus, clathrin works as a regulator of GRK2 in cells. These results indicate that clathrin is a novel player in cellular functions in addition to being a component of endocytosis.", "classifications": [ { "id": "Nishida", "label": "Group Nishida", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Supachoke", "last_name": "Mangmool", "name": null }, { "creator_type": "author", "first_name": "Tatsuya", "last_name": "Haga", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Kyeong-Man", "last_name": "Kim", "name": null }, { "creator_type": "author", "first_name": "Hiroyasu", "last_name": "Nakata", "name": null }, { "creator_type": "author", "first_name": "Motohiro", "last_name": "Nishida", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Kurose", "name": null } ], "identifiers": { "doi": { "normalized": "10.1074/jbc.m602832200" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "16920721" } }, "mesh": [ { "descriptor": "Amino Acid Motifs", "descriptor_ui": "D020816", "major_topic": false }, { "descriptor": "Amino Acid Sequence", "descriptor_ui": "D000595", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "beta-Adrenergic Receptor Kinases", "descriptor_ui": "D051552", "major_topic": false }, { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "Clathrin", "descriptor_ui": "D002966", "major_topic": false }, { "descriptor": "Endocytosis", "descriptor_ui": "D004705", "major_topic": false }, { "descriptor": "G-Protein-Coupled Receptor Kinase 2", "descriptor_ui": "D054769", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Molecular Sequence Data", "descriptor_ui": "D008969", "major_topic": false }, { "descriptor": "Phosphorylation", "descriptor_ui": "D010766", "major_topic": false }, { "descriptor": "Protein Binding", "descriptor_ui": "D011485", "major_topic": false }, { "descriptor": "Protein Conformation", "descriptor_ui": "D011487", "major_topic": false }, { "descriptor": "Receptors, Adrenergic, beta-2", "descriptor_ui": "D018343", "major_topic": false }, { "descriptor": "Sequence Homology, Amino Acid", "descriptor_ui": "D017386", "major_topic": false } ], "publication": { "conference_name": null, "date": "2006 Oct 20", "date_precision": "day", "issue": "42", "normalized_date": "2006-10-20", "pages": "31940-31949", "proceedings_title": null, "publisher": "", "title": "The Journal of biological chemistry", "volume": "281", "year": 2006 }, "ssbd": { "database": [], "repository": [] }, "title": "Clathrin required for phosphorylation and internalization of beta2-adrenergic receptor by G protein-coupled receptor kinase 2 (GRK2).", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "[reaction: see text] We report here the catalytic asymmetric conjugate reduction of enones using ethanol as a hydride source. The reaction was carried out in the presence of a chiral Pd complex at ambient temperature in ethanol, and the desired products were obtained in high chemical yield and high enantioselectivity. We applied this novel reaction to the catalytic asymmetric synthesis of warfarin (96% ee), and on the basis of d-labeling experiments, the reaction mechanism is proposed.", "classifications": [ { "id": "Sodeoka", "label": "Group Sodeoka", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yasunori", "last_name": "Tsuchiya", "name": null }, { "creator_type": "author", "first_name": "Yoshitaka", "last_name": "Hamashima", "name": null }, { "creator_type": "author", "first_name": "Mikiko", "last_name": "Sodeoka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/ol0619157" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "17020319" } }, "mesh": [ { "descriptor": "Catalysis", "descriptor_ui": "D002384", "major_topic": false }, { "descriptor": "Ethanol", "descriptor_ui": "D000431", "major_topic": false }, { "descriptor": "Ketones", "descriptor_ui": "D007659", "major_topic": false }, { "descriptor": "Molecular Structure", "descriptor_ui": "D015394", "major_topic": false }, { "descriptor": "Oxidation-Reduction", "descriptor_ui": "D010084", "major_topic": false }, { "descriptor": "Palladium", "descriptor_ui": "D010165", "major_topic": false }, { "descriptor": "Stereoisomerism", "descriptor_ui": "D013237", "major_topic": false }, { "descriptor": "Warfarin", "descriptor_ui": "D014859", "major_topic": false } ], "publication": { "conference_name": null, "date": "2006 Oct 12", "date_precision": "day", "issue": "21", "normalized_date": "2006-10-12", "pages": "4851-4854", "proceedings_title": null, "publisher": "", "title": "Organic letters", "volume": "8", "year": 2006 }, "ssbd": { "database": [], "repository": [] }, "title": "A new entry to Pd-H chemistry: catalytic asymmetric conjugate reduction of enones with EtOH and a highly enantioselective synthesis of warfarin.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Enteric nervous system (ENS) development requires complex interactions between migrating neural-crest-derived cells and the intestinal microenvironment. Although some molecules influencing ENS development are known, many aspects remain poorly understood. To identify additional molecules critical for ENS development, we used DNA microarray, quantitative real-time PCR and in situ hybridization to compare gene expression in E14 and P0 aganglionic or wild type mouse intestine. Eighty-three genes were identified with at least two-fold higher expression in wild type than aganglionic bowel. ENS expression was verified for 39 of 42 selected genes by in situ hybridization. Additionally, nine identified genes had higher levels in aganglionic bowel than in WT animals suggesting that intestinal innervation may influence gene expression in adjacent cells. Strikingly, many synaptic function genes were expressed at E14, a time when the ENS is not needed for survival. To test for developmental roles for these genes, we used pharmacologic inhibitors of Snap25 or vesicle-associated membrane protein (VAMP)/synaptobrevin and found reduced neural-crest-derived cell migration and decreased neurite extension from ENS precursors. These results provide an extensive set of ENS biomarkers, demonstrate a role for SNARE proteins in ENS development and highlight additional candidate genes that could modify Hirschsprung's disease penetrance.", "classifications": [ { "id": "Enomoto", "label": "Group Enomoto", "parent": "Enomoto", "type": "group" }, { "id": "Enomoto", "label": "Team Enomoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Bhupinder P. S.", "last_name": "Vohra", "name": null }, { "creator_type": "author", "first_name": "Keiji", "last_name": "Tsuji", "name": null }, { "creator_type": "author", "first_name": "Mayumi", "last_name": "Nagashimada", "name": null }, { "creator_type": "author", "first_name": "Toshihiro", "last_name": "Uesaka", "name": null }, { "creator_type": "author", "first_name": "Daniel", "last_name": "Wind", "name": null }, { "creator_type": "author", "first_name": "Ming", "last_name": "Fu", "name": null }, { "creator_type": "author", "first_name": "Jennifer", "last_name": "Armon", "name": null }, { "creator_type": "author", "first_name": "Hideki", "last_name": "Enomoto", "name": null }, { "creator_type": "author", "first_name": "Robert O.", "last_name": "Heuckeroth", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.ydbio.2006.06.033" }, "pmcid": { "normalized": "PMC1952185" }, "pmid": { "normalized": "16904662" } }, "mesh": [ { "descriptor": "alpha Catenin", "descriptor_ui": "D051178", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cadherin Related Proteins", "descriptor_ui": "D000070585", "major_topic": false }, { "descriptor": "Cadherins", "descriptor_ui": "D015820", "major_topic": false }, { "descriptor": "Cell Movement", "descriptor_ui": "D002465", "major_topic": true }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Chromosome Pairing", "descriptor_ui": "D023902", "major_topic": false }, { "descriptor": "Enteric Nervous System", "descriptor_ui": "D017615", "major_topic": false }, { "descriptor": "Epithelium", "descriptor_ui": "D004848", "major_topic": false }, { "descriptor": "Gene Expression", "descriptor_ui": "D015870", "major_topic": false }, { "descriptor": "Hirschsprung Disease", "descriptor_ui": "D006627", "major_topic": false }, { "descriptor": "Intestinal Mucosa", "descriptor_ui": "D007413", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Morphogenesis", "descriptor_ui": "D009024", "major_topic": false }, { "descriptor": "Neurites", "descriptor_ui": "D016501", "major_topic": false }, { "descriptor": "Oligonucleotide Array Sequence Analysis", "descriptor_ui": "D020411", "major_topic": false }, { "descriptor": "Organ Culture Techniques", "descriptor_ui": "D009924", "major_topic": false }, { "descriptor": "Protein Precursors", "descriptor_ui": "D011498", "major_topic": false }, { "descriptor": "Proto-Oncogene Proteins c-ret", "descriptor_ui": "D051096", "major_topic": false }, { "descriptor": "SNARE Proteins", "descriptor_ui": "D050600", "major_topic": false }, { "descriptor": "Stem Cells", "descriptor_ui": "D013234", "major_topic": false } ], "publication": { "conference_name": null, "date": "2006 Oct 1", "date_precision": "day", "issue": "1", "normalized_date": "2006-10-01", "pages": "259-271", "proceedings_title": null, "publisher": "", "title": "Developmental biology", "volume": "298", "year": 2006 }, "ssbd": { "database": [], "repository": [] }, "title": "Differential gene expression and functional analysis implicate novel mechanisms in enteric nervous system precursor migration and neuritogenesis.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Understanding the information processing ability of signal transduction pathways is of great importance because of their crucial roles in triggering various cellular responses. Despite continuing theoretical investigation, some important aspects of signal transduction such as a transient response and its connection to stochasticity originating from a small number of molecules have not yet been well understood. It is, however, through these aspects that unexpected and nontrivial properties of the information processing emerge. In this article, we analyze the transient behavior of a simple signaling cascade by taking into account the stochasticity originating from the small number of molecules. We identify several properties of the signaling cascade that emerge as a result of the interplay between the stochasticity and transient dynamics of the cascade. We specifically demonstrate that each step of the cascade has an optimal number of signaling molecules at which the average signal amplitude becomes maximal. We further investigate the connection between a finite number of molecules and the ability of the cascade to discriminate between true and error signals, which cannot be inferred from deterministic descriptions. The implications of our results are discussed from both biological and mathematical viewpoints.", "classifications": [ { "id": "Kobayashi", "label": "Group Kobayashi", "parent": "Wakamoto", "type": "group" }, { "id": "Wakamoto", "label": "Team Wakamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yoshihiro", "last_name": "Morishita", "name": null }, { "creator_type": "author", "first_name": "Tetsuya J.", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Kazuyuki", "last_name": "Aihara", "name": null } ], "identifiers": { "doi": { "normalized": "10.1529/biophysj.105.070797" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "16798800" } }, "mesh": [ { "descriptor": "Computer Simulation", "descriptor_ui": "D003198", "major_topic": true }, { "descriptor": "Models, Biological", "descriptor_ui": "D008954", "major_topic": true }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": true }, { "descriptor": "Stochastic Processes", "descriptor_ui": "D013269", "major_topic": false } ], "publication": { "conference_name": null, "date": "2006 Sep 15", "date_precision": "day", "issue": "6", "normalized_date": "2006-09-15", "pages": "2072-2081", "proceedings_title": null, "publisher": "", "title": "Biophysical Journal", "volume": "91", "year": 2006 }, "ssbd": { "database": [], "repository": [] }, "title": "An Optimal Number of Molecules for Signal Amplification and Discrimination in a Chemical Cascade.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Hydrocephalus is a common and variegated pathology often emerging in newborn children after genotoxic insults during pregnancy (Hicks and D’Amato, 1980). Cre recombinase is known to have possible toxic effects that can compromise normal cell cycle and survival. Here we show, by using three independent nestin Cre transgenic lines, that high levels of Cre recombinase expression into the nucleus of neuronal progenitors can compromise normal brain development. The transgenics analyzed are the nestin Cre Balancer (Bal1) line, expressing the Cre recombinase with a nuclear localization signal, and two nestin CreERT2 (Cre recombinase fused with a truncated estrogen receptor) mice lines with different levels of expression of a hybrid CreERT2 recombinase that translocates into the nucleus after tamoxifen treatment. All homozygous Bal1 nestin Cre embryos displayed reduced neuronal proliferation, increased aneuploidy and cell death, as well as defects in ependymal lining and lamination of the cortex, leading to microencephaly and to a form of communicating hydrocephalus. An essentially overlapping phenotype was observed in the two nestin CreERT2 transgenic lines after tamoxifen mediated-CreERT2 translocation into the nucleus. Neither tamoxifen-treated wild-type nor nestin CreERT2 oil-treated control mice displayed these defects. These results indicate that some forms of hydrocephalus may derive from a defect in neuronal precursors proliferation. Furthermore, they underscore the potential risks for developmental studies of high levels of nuclear Cre in neurogenic cells.", "classifications": [ { "id": "Imayoshi", "label": "Group Imayoshi", "parent": "Imayoshi", "type": "group" }, { "id": "Imayoshi", "label": "Team Imayoshi", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Paolo E.", "last_name": "Forni", "name": null }, { "creator_type": "author", "first_name": "Claudio", "last_name": "Scuoppo", "name": null }, { "creator_type": "author", "first_name": "Itaru", "last_name": "Imayoshi", "name": null }, { "creator_type": "author", "first_name": "Riccardo", "last_name": "Taulli", "name": null }, { "creator_type": "author", "first_name": "Walter", "last_name": "Dastrù", "name": null }, { "creator_type": "author", "first_name": "Valentina", "last_name": "Sala", "name": null }, { "creator_type": "author", "first_name": "Ulrich A. K.", "last_name": "Betz", "name": null }, { "creator_type": "author", "first_name": "Patrizia", "last_name": "Muzzi", "name": null }, { "creator_type": "author", "first_name": "Daniela", "last_name": "Martinuzzi", "name": null }, { "creator_type": "author", "first_name": "Alessandro E.", "last_name": "Vercelli", "name": null }, { "creator_type": "author", "first_name": "Ryoichiro", "last_name": "Kageyama", "name": null }, { "creator_type": "author", "first_name": "Carola", "last_name": "Ponzetto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1523/jneurosci.2815-06.2006" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "16971543" } }, "mesh": [ { "descriptor": "Aneuploidy", "descriptor_ui": "D000782", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Biomarkers", "descriptor_ui": "D015415", "major_topic": false }, { "descriptor": "Brain", "descriptor_ui": "D001921", "major_topic": false }, { "descriptor": "Cell Death", "descriptor_ui": "D016923", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Cell Proliferation", "descriptor_ui": "D049109", "major_topic": false }, { "descriptor": "Ependyma", "descriptor_ui": "D004805", "major_topic": false }, { "descriptor": "Gene Expression Regulation, Developmental", "descriptor_ui": "D018507", "major_topic": false }, { "descriptor": "Hydrocephalus", "descriptor_ui": "D006849", "major_topic": false }, { "descriptor": "Integrases", "descriptor_ui": "D019426", "major_topic": false }, { "descriptor": "Intermediate Filament Proteins", "descriptor_ui": "D007381", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Transgenic", "descriptor_ui": "D008822", "major_topic": false }, { "descriptor": "Microcephaly", "descriptor_ui": "D008831", "major_topic": false }, { "descriptor": "Nerve Tissue Proteins", "descriptor_ui": "D009419", "major_topic": false }, { "descriptor": "Nervous System Malformations", "descriptor_ui": "D009421", "major_topic": false }, { "descriptor": "Nestin", "descriptor_ui": "D064231", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Nuclear Localization Signals", "descriptor_ui": "D019913", "major_topic": false }, { "descriptor": "Receptors, Estrogen", "descriptor_ui": "D011960", "major_topic": false }, { "descriptor": "Selective Estrogen Receptor Modulators", "descriptor_ui": "D020845", "major_topic": false }, { "descriptor": "Stem Cells", "descriptor_ui": "D013234", "major_topic": false }, { "descriptor": "Tamoxifen", "descriptor_ui": "D013629", "major_topic": false } ], "publication": { "conference_name": null, "date": "2006 Sep 13", "date_precision": "day", "issue": "37", "normalized_date": "2006-09-13", "pages": "9593-9602", "proceedings_title": null, "publisher": "", "title": "The Journal of Neuroscience", "volume": "26", "year": 2006 }, "ssbd": { "database": [], "repository": [] }, "title": "High Levels of Cre Expression in Neuronal Progenitors Cause Defects in Brain Development Leading to Microencephaly and Hydrocephaly.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "In the intrinsic pathway of apoptosis, mitochondria play a crucial role by releasing cytochrome c from the intermembrane space into the cytoplasm. Cytochrome c release through Bax/Bak-dependent channels in mitochondria has been well documented. In contrast, cyclophilin D (CypD), an important component of permeability transition pore-dependent protein release, remains largely undefined, and no apoptogenic proteins that act specifically in a CypD-dependent manner have been reported to date. Here, we describe a novel and evolutionarily conserved protein, apoptogenic protein (Apop). Mouse Apop-1 expression induces apoptotic death by releasing cytochrome c from mitochondria into the cytosolic space followed by activation of caspase-9 and -3. Apop-1-induced apoptosis is not blocked by Bcl-2 or Bcl-xL, inhibitors of Bax/Bak-dependent channels, whereas it is completely blocked by cyclosporin A, an inhibitor of permeability transition pore. Cells lacking CypD were resistant to Apop-induced apoptosis. Moreover, inhibition of Apop expression prevented the cell death induced by apoptosis-inducing substances. Our findings, thus, indicate that the expression of Apop-1 induces apoptosis though CypD-dependent pathway and that Apop-1 plays roles in cell death under physiological conditions.", "classifications": [ { "id": "Suzuki", "label": "Group Suzuki", "parent": "Takekawa", "type": "group" }, { "id": "Takekawa", "label": "Team Takekawa", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Osamu", "last_name": "Yasuda", "name": null }, { "creator_type": "author", "first_name": "Keisuke", "last_name": "Fukuo", "name": null }, { "creator_type": "author", "first_name": "Xin", "last_name": "Sun", "name": null }, { "creator_type": "author", "first_name": "Masahito", "last_name": "Nishitani", "name": null }, { "creator_type": "author", "first_name": "Takamori", "last_name": "Yotsui", "name": null }, { "creator_type": "author", "first_name": "Masayoshi", "last_name": "Higuchi", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Hiromi", "last_name": "Rakugi", "name": null }, { "creator_type": "author", "first_name": "Oliver", "last_name": "Smithies", "name": null }, { "creator_type": "author", "first_name": "Nobuyo", "last_name": "Maeda", "name": null }, { "creator_type": "author", "first_name": "Toshio", "last_name": "Ogihara", "name": null } ], "identifiers": { "doi": { "normalized": "10.1074/jbc.m512610200" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "16782708" } }, "mesh": [ { "descriptor": "Amino Acid Sequence", "descriptor_ui": "D000595", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Apoptosis", "descriptor_ui": "D017209", "major_topic": false }, { "descriptor": "Apoptosis Regulatory Proteins", "descriptor_ui": "D051017", "major_topic": false }, { "descriptor": "bcl-2 Homologous Antagonist-Killer Protein", "descriptor_ui": "D050998", "major_topic": false }, { "descriptor": "bcl-2-Associated X Protein", "descriptor_ui": "D051028", "major_topic": false }, { "descriptor": "Caspase 3", "descriptor_ui": "D053148", "major_topic": false }, { "descriptor": "Caspase 9", "descriptor_ui": "D053453", "major_topic": false }, { "descriptor": "Caspases", "descriptor_ui": "D020169", "major_topic": false }, { "descriptor": "Cell Death", "descriptor_ui": "D016923", "major_topic": false }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Cyclophilins", "descriptor_ui": "D021983", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Ion Channels", "descriptor_ui": "D007473", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Mitochondrial Proteins", "descriptor_ui": "D024101", "major_topic": false }, { "descriptor": "Molecular Sequence Data", "descriptor_ui": "D008969", "major_topic": false }, { "descriptor": "Peptidyl-Prolyl Isomerase F", "descriptor_ui": "D000081406", "major_topic": false } ], "publication": { "conference_name": null, "date": "2006 Aug 18", "date_precision": "day", "issue": "33", "normalized_date": "2006-08-18", "pages": "23899-23907", "proceedings_title": null, "publisher": "", "title": "The Journal of biological chemistry", "volume": "281", "year": 2006 }, "ssbd": { "database": [], "repository": [] }, "title": "Apop-1, a novel protein inducing cyclophilin D-dependent but Bax/Bak-related channel-independent apoptosis.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "To understand the control mechanism of innate immune response in macrophages, a series of phagocytic responses to plural stimulation of antigens on identical cells was observed. Two zymosan particles, which were used as antigens, were put on different surfaces of a macrophage using optical tweezers in an on-chip single-cell cultivation system, which maintains isolated conditions of each macrophage during their cultivation. When the two zymosan particles were attached to the macrophage simultaneously, the macrophage responded and phagocytosed both of the antigens simultaneously. In contrast, when the second antigen was attached to the surface after the first phagocytosis had started, the macrophage did not respond to the second stimulation during the first phagocytosis; the second phagocytosis started only after the first process had finished. These results indicate that (i) phagocytosis in a macrophage is not an independent process when there are plural stimulations; (ii) the response of the macrophage to the second stimulation is related to the time\" delay from the first stimulation. Stimulations that occur at short time intervals resulted in simultaneous phagocytosis, while a second stimulation that is delayed long enough might be neglected until the completion of the first phagocytic process.", "classifications": [ { "id": "Wakamoto", "label": "Group Wakamoto", "parent": "Wakamoto", "type": "group" }, { "id": "Wakamoto", "label": "Team Wakamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Kazunori", "last_name": "Matsumura", "name": null }, { "creator_type": "author", "first_name": "Kazuki", "last_name": "Orita", "name": null }, { "creator_type": "author", "first_name": "Yuichi", "last_name": "Wakamoto", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Yasuda", "name": null } ], "identifiers": { "doi": { "normalized": "10.1186/1477-3155-4-7" }, "pmcid": { "normalized": "PMC1564038" }, "pmid": { "normalized": "16914039" } }, "mesh": [], "publication": { "conference_name": null, "date": "2006 Aug 16", "date_precision": "day", "issue": "", "normalized_date": "2006-08-16", "pages": "7", "proceedings_title": null, "publisher": "", "title": "Journal of nanobiotechnology", "volume": "4", "year": 2006 }, "ssbd": { "database": [], "repository": [] }, "title": "Phagocytic response to fully controlled plural stimulation of antigens on macrophage using on-chip microcultivation system.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "PURPOSE: Survivin is one of the apoptosis inhibitor genes and is rarely expressed in adult -tissues. However, survivin expression has been detected in various human cancers and -correlations have been recognized between the level of expression of this gene in tumors and prognosis. In this study, we investigated the correlations between survivin mRNA expression in osteosarcoma tissues and clinicopathological parameters. METHODS: There were 22 osteosarcoma patients in our hospital with paraffin-embedded -tissues which could be extracted from biopsy specimens. We used the RT-PCR method after extracting total RNA and conducted a densitometric analysis to determine the ratio of survivin relative to h-GAPDH as an internal marker. RESULTS: Expression of survivin mRNA was detected in all osteosarcoma samples. Patients with metastasis had high survivin mRNA levels in initial biopsy specimens (p<0.01). Moreover, there was a statistically significant difference in survivin mRNA expression between -patients with and without metastasis (p<0.01). CONCLUSION: We concluded that high levels of survivin mRNA expression suggest poor prognosis for osteosarcoma patients.", "classifications": [ { "id": "Suzuki", "label": "Group Suzuki", "parent": "Takekawa", "type": "group" }, { "id": "Takekawa", "label": "Team Takekawa", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Eiji", "last_name": "Osaka", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Shunzo", "last_name": "Osaka", "name": null }, { "creator_type": "author", "first_name": "Yukihiro", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Hideyuki", "last_name": "Sugita", "name": null }, { "creator_type": "author", "first_name": "Satoru", "last_name": "Asami", "name": null }, { "creator_type": "author", "first_name": "Keiichi", "last_name": "Tabata", "name": null }, { "creator_type": "author", "first_name": "Akihiro", "last_name": "Hemmi", "name": null }, { "creator_type": "author", "first_name": "Masahiko", "last_name": "Sugitani", "name": null }, { "creator_type": "author", "first_name": "Norimichi", "last_name": "Nemoto", "name": null }, { "creator_type": "author", "first_name": "Junnosuke", "last_name": "Ryu", "name": null } ], "identifiers": { "doi": { "normalized": "10.1267/ahc.06005" }, "pmcid": { "normalized": "PMC1790971" }, "pmid": { "normalized": "17327929" } }, "mesh": [], "publication": { "conference_name": null, "date": "2006 Jul 1", "date_precision": "day", "issue": "3", "normalized_date": "2006-07-01", "pages": "95-100", "proceedings_title": null, "publisher": "", "title": "Acta histochemica et cytochemica", "volume": "39", "year": 2006 }, "ssbd": { "database": [], "repository": [] }, "title": "Survivin as a prognostic factor for osteosarcoma patients.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: The ERK family of MAP kinase plays a critical role in growth factor-stimulated cell-cycle progression from G0/G1 to S phase. It has been suggested that sustained activation, but not transient activation, of ERK is necessary for inducing S phase entry. Although the essential role of ERK MAP kinase in growth factor-stimulated gene expression, especially expression of immediate-early genes, is well established, it has remained unclear how ERK activity duration affects the promotion of G1 phase progression to S phase. RESULTS: We have found that inhibition of ERK activation by the MEK inhibitor or dominant-negative MEK1 even immediately before the onset of S phase leads to the cessation of S phase entry. Our analyses reveal that there are ERK-dependent downregulated genes, whose expression levels return to their original levels rapidly after ERK inactivation, and that their downregulation mostly requires AP-1 activity. Remarkably, microinjection experiments demonstrate that many of the downregulated genes act as antiproliferative genes during G1 phase and that their forced expression to the levels before growth factor stimulation even in late G1 phase blocks S phase entry. CONCLUSIONS: Thus, continuous ERK activation downregulates antiproliferative genes until the onset of S phase to allow successful G1 phase progression. This mechanism may also work as a fail-safe mechanism, which prevents inappropriate stimuli that induce transient ERK activation from causing S phase entry.", "classifications": [ { "id": "Yamamoto", "label": "Group Yamamoto", "parent": "Toyoshima", "type": "group" }, { "id": "Toyoshima", "label": "Team Toyoshima", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Takuya", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Miki", "last_name": "Ebisuya", "name": null }, { "creator_type": "author", "first_name": "Fumito", "last_name": "Ashida", "name": null }, { "creator_type": "author", "first_name": "Kazuo", "last_name": "Okamoto", "name": null }, { "creator_type": "author", "first_name": "Shin", "last_name": "Yonehara", "name": null }, { "creator_type": "author", "first_name": "Eisuke", "last_name": "Nishida", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.cub.2006.04.044" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "16782007" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Proliferation", "descriptor_ui": "D049109", "major_topic": false }, { "descriptor": "Down-Regulation", "descriptor_ui": "D015536", "major_topic": true }, { "descriptor": "Extracellular Signal-Regulated MAP Kinases", "descriptor_ui": "D048049", "major_topic": false }, { "descriptor": "G1 Phase", "descriptor_ui": "D016193", "major_topic": false }, { "descriptor": "Gene Expression Profiling", "descriptor_ui": "D020869", "major_topic": false }, { "descriptor": "Genes, cdc", "descriptor_ui": "D018816", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "NIH 3T3 Cells", "descriptor_ui": "D041681", "major_topic": false }, { "descriptor": "S Phase", "descriptor_ui": "D016196", "major_topic": false }, { "descriptor": "Transcription Factor AP-1", "descriptor_ui": "D018808", "major_topic": false } ], "publication": { "conference_name": null, "date": "2006 Jun 20", "date_precision": "day", "issue": "12", "normalized_date": "2006-06-20", "pages": "1171-1182", "proceedings_title": null, "publisher": "", "title": "Current biology : CB", "volume": "16", "year": 2006 }, "ssbd": { "database": [], "repository": [] }, "title": "Continuous ERK activation downregulates antiproliferative genes throughout G1 phase to allow cell-cycle progression.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Metabolomics is an emerging tool that can be used to gain insights into cellular and physiological responses. Here we present a metabolome differential display method based on capillary electrophoresis time-of-flight mass spectrometry to profile liver metabolites following acetaminophen-induced hepatotoxicity. We globally detected 1,859 peaks in mouse liver extracts and highlighted multiple changes in metabolite levels, including an activation of the ophthalmate biosynthesis pathway. We confirmed that ophthalmate was synthesized from 2-aminobutyrate through consecutive reactions with gamma-glutamylcysteine and glutathione synthetase. Changes in ophthalmate level in mouse serum and liver extracts were closely correlated and ophthalmate levels increased significantly in conjunction with glutathione consumption. Overall, our results provide a broad picture of hepatic metabolite changes following acetaminophen treatment. In addition, we specifically found that serum ophthalmate is a sensitive indicator of hepatic GSH depletion, and may be a new biomarker for oxidative stress. Our method can thus pinpoint specific metabolite changes and provide insights into the perturbation of metabolic pathways on a large scale and serve as a powerful new tool for discovering low molecular weight biomarkers.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Richard", "last_name": "Baran", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Suematsu", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Ueno", "name": null }, { "creator_type": "author", "first_name": "Satsuki", "last_name": "Ikeda", "name": null }, { "creator_type": "author", "first_name": "Tadayuki", "last_name": "Sakurakawa", "name": null }, { "creator_type": "author", "first_name": "Yuji", "last_name": "Kakazu", "name": null }, { "creator_type": "author", "first_name": "Takamasa", "last_name": "Ishikawa", "name": null }, { "creator_type": "author", "first_name": "Martin", "last_name": "Robert", "name": null }, { "creator_type": "author", "first_name": "Takaaki", "last_name": "Nishioka", "name": null }, { "creator_type": "author", "first_name": "Masaru", "last_name": "Tomita", "name": null } ], "identifiers": { "doi": { "normalized": "10.1074/jbc.m601876200" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "16608839" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Dipeptides", "descriptor_ui": "D004151", "major_topic": false }, { "descriptor": "Electrophoresis, Capillary", "descriptor_ui": "D019075", "major_topic": false }, { "descriptor": "Gene Expression Profiling", "descriptor_ui": "D020869", "major_topic": false }, { "descriptor": "Glutathione", "descriptor_ui": "D005978", "major_topic": false }, { "descriptor": "Glutathione Synthase", "descriptor_ui": "D005981", "major_topic": false }, { "descriptor": "Liver", "descriptor_ui": "D008099", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Metabolism", "descriptor_ui": "D008660", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Models, Biological", "descriptor_ui": "D008954", "major_topic": false }, { "descriptor": "Oligopeptides", "descriptor_ui": "D009842", "major_topic": false }, { "descriptor": "Oxidative Stress", "descriptor_ui": "D018384", "major_topic": true } ], "publication": { "conference_name": null, "date": "2006 Jun 16", "date_precision": "day", "issue": "24", "normalized_date": "2006-06-16", "pages": "16768-16776", "proceedings_title": null, "publisher": "", "title": "The Journal of biological chemistry", "volume": "281", "year": 2006 }, "ssbd": { "database": [], "repository": [] }, "title": "Differential metabolomics reveals ophthalmic acid as an oxidative stress biomarker indicating hepatic glutathione consumption.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The hippocampal formation and amygdala are responsible for regulating emotion, learning, and behavior. The hippocampal projection to the amygdala has been demonstrated to originate in the subiculum and adjacent portion of field CA1 of the Ammon's horn (Sub/CA1) in the rat; however, the topographical organization of this pathway is still understudied. To make it clear, we performed anterograde and retrograde tracing with biotinylated dextran amine (BDA) and cholera toxin B subunit (CTb), respectively, in the rat. A series of BDA experiments revealed that the temporal-to-septal axis of origin determined a medial-to-lateral axis of termination in the amygdala. Briefly, the temporal region of the Sub/CA1 projects preferentially to the medial amygdaloid region including the medial, intercalated, and basomedial nuclei and the amygdalohippocampal transition area, and progressively more septal portions of the Sub/CA1 distribute their efferents in more lateral regions of the amygdala. Sub/CA1 fibers distributed in the central amygdaloid nucleus were relatively few. Retrograde tracing with CTb confirmed this topography and revealed little hippocampal innervation of the central nucleus of the amygdala. These observations suggest that distinct Sub/CA1 regions arranged along the longitudinal hippocampal axis may influence distinct modalities of the amygdala function.", "classifications": [ { "id": "Yokota", "label": "Group Yokota", "parent": "Enomoto", "type": "group" }, { "id": "Enomoto", "label": "Team Enomoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Toshiro", "last_name": "Kishi", "name": null }, { "creator_type": "author", "first_name": "Toshiko", "last_name": "Tsumori", "name": null }, { "creator_type": "author", "first_name": "Shigefumi", "last_name": "Yokota", "name": null }, { "creator_type": "author", "first_name": "Yukihiko", "last_name": "Yasui", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/cne.20919" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "16566004" } }, "mesh": [ { "descriptor": "Amygdala", "descriptor_ui": "D000679", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Biotin", "descriptor_ui": "D001710", "major_topic": false }, { "descriptor": "Brain Mapping", "descriptor_ui": "D001931", "major_topic": true }, { "descriptor": "Cholera Toxin", "descriptor_ui": "D002772", "major_topic": false }, { "descriptor": "Dextrans", "descriptor_ui": "D003911", "major_topic": false }, { "descriptor": "Fluorescent Dyes", "descriptor_ui": "D005456", "major_topic": false }, { "descriptor": "Hippocampus", "descriptor_ui": "D006624", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Neural Pathways", "descriptor_ui": "D009434", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Rats, Wistar", "descriptor_ui": "D017208", "major_topic": false } ], "publication": { "conference_name": null, "date": "2006 May 20", "date_precision": "day", "issue": "3", "normalized_date": "2006-05-20", "pages": "349-368", "proceedings_title": null, "publisher": "", "title": "The Journal of comparative neurology", "volume": "496", "year": 2006 }, "ssbd": { "database": [], "repository": [] }, "title": "Topographical projection from the hippocampal formation to the amygdala: a combined anterograde and retrograde tracing study in the rat.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Although Turing pattern is one of the most universal mechanisms for pattern formation, in its standard model the number of stripes changes with the system size, since the wavelength of the pattern is invariant. It fails to preserve the proportionality of the pattern, i.e. the ratio of the wavelength to the size, that is often required in biological morphogenesis. To get over this problem, we show that the Turing pattern can preserve proportionality by introducing a catalytic chemical whose concentration depends on the system size. Several plausible mechanisms for such size dependence of the concentration are discussed. Following this general discussion, two models are studied in which arising Turing patterns indeed preserve the proportionality. Relevance of the present mechanism to biological morphogenesis is discussed from the viewpoint of its generality, robustness, and evolutionary accessibility.", "classifications": [ { "id": "Ishihara", "label": "Group Ishihara", "parent": "Sawai", "type": "group" }, { "id": "Sawai", "label": "Team Sawai", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Shuji", "last_name": "Ishihara", "name": null }, { "creator_type": "author", "first_name": "Kunihiko", "last_name": "Kaneko", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.jtbi.2005.06.016" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "16098989" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Body Patterning", "descriptor_ui": "D019521", "major_topic": false }, { "descriptor": "Body Size", "descriptor_ui": "D049628", "major_topic": false }, { "descriptor": "Computational Biology", "descriptor_ui": "D019295", "major_topic": false }, { "descriptor": "Computer Simulation", "descriptor_ui": "D003198", "major_topic": true }, { "descriptor": "Models, Biological", "descriptor_ui": "D008954", "major_topic": false } ], "publication": { "conference_name": null, "date": "2006 Feb 7", "date_precision": "day", "issue": "3", "normalized_date": "2006-02-07", "pages": "683-693", "proceedings_title": null, "publisher": "", "title": "Journal of theoretical biology", "volume": "238", "year": 2006 }, "ssbd": { "database": [], "repository": [] }, "title": "Turing pattern with proportion preservation.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "After ipsilateral injections of cholera toxin B subunit (CTb) into the nucleus of the solitary tract (NST) and biotinylated dextran amine (BDA) into the insular cortex (IC) or into the central amygdaloid nucleus (ACe) in the rat, the prominent overlapping distribution of CTb-labeled neurons and BDA-labeled axon terminals was found in the posterolateral hypothalamus (PLH) region just medial to the subthalamic nucleus ipsilateral to the injection sites. At the electron microscopic level, the IC terminals formed asymmetrical synaptic contacts with dendrites and dendritic spines of the NST-projecting PLH neurons, whereas the ACe terminals formed symmetrical synaptic contacts with somata and dendrites of the NST-projecting PLH neurons. The present data suggest that output signals from the IC and ACe may exert excitatory and inhibitory influences, respectively, upon the PLH neurons that project to the NST for regulating cardiovascular functions.", "classifications": [ { "id": "Yokota", "label": "Group Yokota", "parent": "Enomoto", "type": "group" }, { "id": "Enomoto", "label": "Team Enomoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Toshiko", "last_name": "Tsumori", "name": null }, { "creator_type": "author", "first_name": "Shigefumi", "last_name": "Yokota", "name": null }, { "creator_type": "author", "first_name": "Toshiro", "last_name": "Kishi", "name": null }, { "creator_type": "author", "first_name": "Yi", "last_name": "Qin", "name": null }, { "creator_type": "author", "first_name": "Tatsuro", "last_name": "Oka", "name": null }, { "creator_type": "author", "first_name": "Yukihiko", "last_name": "Yasui", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.brainres.2005.11.040" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "16388783" } }, "mesh": [ { "descriptor": "Amygdala", "descriptor_ui": "D000679", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Biotin", "descriptor_ui": "D001710", "major_topic": false }, { "descriptor": "Cerebral Cortex", "descriptor_ui": "D002540", "major_topic": false }, { "descriptor": "Cholera Toxin", "descriptor_ui": "D002772", "major_topic": false }, { "descriptor": "Dextrans", "descriptor_ui": "D003911", "major_topic": false }, { "descriptor": "Fluorescent Dyes", "descriptor_ui": "D005456", "major_topic": false }, { "descriptor": "Hypothalamic Area, Lateral", "descriptor_ui": "D007026", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Microscopy, Electron", "descriptor_ui": "D008854", "major_topic": false }, { "descriptor": "Nerve Fibers", "descriptor_ui": "D009412", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Presynaptic Terminals", "descriptor_ui": "D017729", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Rats, Wistar", "descriptor_ui": "D017208", "major_topic": false }, { "descriptor": "Solitary Nucleus", "descriptor_ui": "D017552", "major_topic": false }, { "descriptor": "Synaptic Transmission", "descriptor_ui": "D009435", "major_topic": false } ], "publication": { "conference_name": null, "date": "2006 Jan 27", "date_precision": "day", "issue": "1", "normalized_date": "2006-01-27", "pages": "139-144", "proceedings_title": null, "publisher": "", "title": "Brain research", "volume": "1070", "year": 2006 }, "ssbd": { "database": [], "repository": [] }, "title": "Insular cortical and amygdaloid fibers are in contact with posterolateral hypothalamic neurons projecting to the nucleus of the solitary tract in the rat.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The calcium ion (Ca(2+)) concentrations in a cell are responsible for the control of vital cellular functions and have been widely studied as a means to investigate and control cell activities. Here, we demonstrate Ca(2+) wave generation in HeLa cells by femtosecond laser irradiation and show unexpected properties of the Ca(2+) release and propagation. When the laser was focused in the cell cytoplasm, Ca(2+) release was independent of both external Ca(2+) influx and the phosphoinositide-phospholipase C (PLC) signaling pathway. The nucleus was not a susceptible target for laser-induced Ca(2+) release, whereas irradiation of the plasma membrane produced evidence of transient poration, through which the extracellular solution could enter the cell. By chelating extracellular Ca(2+), we found that laser-induced influx of ethylene glycol tetra-acetic acid (EGTA) can compete with calcium induced calcium release and significantly delay or suppress the onset of the Ca(2+) wave in the target cell. Intercellular Ca(2+) propagation was adenosine triphosphate-dependent and could be observed even when the target cell cytosolic Ca(2+) rise was suppressed by influx of EGTA. The irradiation effect on overall cell viability was also tested and found to be low (85% at 6 h after irradiation by 60 mW average power). Laser-induced Ca(2+) waves can be reliably generated by controlling the exposure and focal position and do not require the presence of caged Ca(2+). The technique has the potential to replace other methods of Ca(2+) stimulation, which either require additional caged molecules in the cell or do not have an interaction that is as well localized.", "classifications": [ { "id": "Fujita", "label": "Group Fujita", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Shigeki", "last_name": "Iwanaga", "name": null }, { "creator_type": "author", "first_name": "Tomoyuki", "last_name": "Kaneko", "name": null }, { "creator_type": "author", "first_name": "Katsumasa", "last_name": "Fujita", "name": null }, { "creator_type": "author", "first_name": "Nicholas", "last_name": "Smith", "name": null }, { "creator_type": "author", "first_name": "Osamu", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Tetsuro", "last_name": "Takamatsu", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Kawata", "name": null } ], "identifiers": { "doi": { "normalized": "10.1385/cbb:45:2:167" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "16757817" } }, "mesh": [ { "descriptor": "Adenosine Triphosphate", "descriptor_ui": "D000255", "major_topic": false }, { "descriptor": "Binding, Competitive", "descriptor_ui": "D001667", "major_topic": false }, { "descriptor": "Calcium", "descriptor_ui": "D002118", "major_topic": false }, { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "Chelating Agents", "descriptor_ui": "D002614", "major_topic": false }, { "descriptor": "Cytoplasm", "descriptor_ui": "D003593", "major_topic": false }, { "descriptor": "Dose-Response Relationship, Radiation", "descriptor_ui": "D004307", "major_topic": false }, { "descriptor": "Egtazic Acid", "descriptor_ui": "D004533", "major_topic": false }, { "descriptor": "HeLa Cells", "descriptor_ui": "D006367", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Lasers", "descriptor_ui": "D007834", "major_topic": true }, { "descriptor": "Phosphatidylinositols", "descriptor_ui": "D010716", "major_topic": false }, { "descriptor": "Photic Stimulation", "descriptor_ui": "D010775", "major_topic": true }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Type C Phospholipases", "descriptor_ui": "D010738", "major_topic": false } ], "publication": { "conference_name": null, "date": "2006", "date_precision": "year", "issue": "2", "normalized_date": "2006", "pages": "167-176", "proceedings_title": null, "publisher": "", "title": "Cell biochemistry and biophysics", "volume": "45", "year": 2006 }, "ssbd": { "database": [], "repository": [] }, "title": "Location-dependent photogeneration of calcium waves in HeLa cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Background: Protein identification based on mass spectrometry (MS) has previously been performed using peptide mass fingerprinting (PMF) or tandem MS (MS/MS) database searching. However, these methods cannot identify proteins that are not already listed in existing databases. Moreover, the alternative approach of de novo sequencing requires costly equipment and the interpretation of complex MS/MS spectra. Thus, there is a need for novel high-throughput protein-identification methods that are independent of existing predefined protein databases. Results: Here, we present a hybrid method for genome-fingerprint scanning, known as HybGFS. This technique combines genome sequence-based peptide MS/MS ion searching with liquid-chromatography elution-time (LC-ET) prediction, to improve the reliability of identification. The hybrid method allows the simultaneous identification and mapping of proteins without a priori information about their coding sequences. The current study used standard LC-MS/MS data to query an in silico-generated six-reading-frame translation and the enzymatic digest of an entire genome. Used in conjunction with precursor/product ion-mass searching, the LC-ETs increased confidence in the peptide-identification process and reduced the number of false-positive matches. The power of this method was demonstrated using recombinant proteins from the Escherichia coli K12 strain. Conclusion: The novel hybrid method described in this study will be useful for the large-scale experimental confirmation of genome coding sequences, without the need for transcriptome-level expression analysis or costly MS database searching.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Kosaku", "last_name": "Shinoda", "name": null }, { "creator_type": "author", "first_name": "Nozomu", "last_name": "Yachie", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Masuda", "name": null }, { "creator_type": "author", "first_name": "Naoyuki", "last_name": "Sugiyama", "name": null }, { "creator_type": "author", "first_name": "Masahiro", "last_name": "Sugimoto", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Masaru", "last_name": "Tomita", "name": null } ], "identifiers": { "doi": { "normalized": "10.1186/1471-2105-7-479" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "17069662" } }, "mesh": [ { "descriptor": "Algorithms", "descriptor_ui": "D000465", "major_topic": false }, { "descriptor": "Chromatography, Liquid", "descriptor_ui": "D002853", "major_topic": true }, { "descriptor": "Databases, Genetic", "descriptor_ui": "D030541", "major_topic": false }, { "descriptor": "Escherichia coli Proteins", "descriptor_ui": "D029968", "major_topic": false }, { "descriptor": "Genes, Bacterial", "descriptor_ui": "D005798", "major_topic": true }, { "descriptor": "Peptide Mapping", "descriptor_ui": "D010449", "major_topic": false }, { "descriptor": "Recombinant Proteins", "descriptor_ui": "D011994", "major_topic": false }, { "descriptor": "Reproducibility of Results", "descriptor_ui": "D015203", "major_topic": false }, { "descriptor": "Sequence Analysis, Protein", "descriptor_ui": "D020539", "major_topic": false }, { "descriptor": "Software", "descriptor_ui": "D012984", "major_topic": false }, { "descriptor": "Tandem Mass Spectrometry", "descriptor_ui": "D053719", "major_topic": true }, { "descriptor": "Time Factors", "descriptor_ui": "D013997", "major_topic": false } ], "publication": { "conference_name": null, "date": "2006", "date_precision": "year", "issue": "", "normalized_date": "2006", "pages": "479", "proceedings_title": null, "publisher": "", "title": "BMC Bioinformatics", "volume": "7", "year": 2006 }, "ssbd": { "database": [], "repository": [] }, "title": "HybGFS: a hybrid method for genome-fingerprint scanning.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Sustained contraction of cells depends on sustained Rho-associated kinase (Rho-kinase) activation. We developed a computational model of the Rho-kinase pathway to understand the systems characteristics. Thrombin-dependent in vivo transient responses of Rho activation and Ca2+ increase could be reproduced in silico. Low and high thrombin stimulation induced transient and sustained phosphorylation, respectively, of myosin light chain (MLC) and myosin phosphatase targeting subunit 1 (MYPT1) in vivo. The transient phosphorylation of MLC and MYPT1 could be reproduced in silico, but their sustained phosphorylation could not. This discrepancy between in vivo and in silico in the sustained responses downstream of Rho-kinase indicates that a missing pathway(s) may be responsible for the sustained Rho-kinase activation. We found, experimentally, that the sustained phosphorylation of MLC and MYPT1 exhibit all-or-none responses. Bromoenol lactone, a specific inhibitor of Ca2+ -independent phospholipase A2 (iPLA2), inhibited sustained phosphorylation of MLC and MYPT1, which indicates that sustained Rho-kinase activation requires iPLA2 activity. Thus, the systems analysis of the Rho-kinase pathway identified a novel iPLA2-dependent mechanism of the sustained Rho-kinase activation, which exhibits an all-or-none response.", "classifications": [ { "id": "Kuroda", "label": "Group Kuroda", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Akio", "last_name": "Maeda", "name": null }, { "creator_type": "author", "first_name": "Yu-ichi", "last_name": "Ozaki", "name": null }, { "creator_type": "author", "first_name": "Sudhir", "last_name": "Sivakumaran", "name": null }, { "creator_type": "author", "first_name": "Tetsuro", "last_name": "Akiyama", "name": null }, { "creator_type": "author", "first_name": "Hidetoshi", "last_name": "Urakubo", "name": null }, { "creator_type": "author", "first_name": "Ayako", "last_name": "Usami", "name": null }, { "creator_type": "author", "first_name": "Miharu", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Kozo", "last_name": "Kaibuchi", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Kuroda", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/j.1365-2443.2006.01001.x" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "16923126" } }, "mesh": [ { "descriptor": "Calcium", "descriptor_ui": "D002118", "major_topic": false }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Computer Simulation", "descriptor_ui": "D003198", "major_topic": true }, { "descriptor": "Dose-Response Relationship, Drug", "descriptor_ui": "D004305", "major_topic": false }, { "descriptor": "Endothelial Cells", "descriptor_ui": "D042783", "major_topic": false }, { "descriptor": "Enzyme Activation", "descriptor_ui": "D004789", "major_topic": false }, { "descriptor": "Group IV Phospholipases A2", "descriptor_ui": "D054513", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Intracellular Signaling Peptides and Proteins", "descriptor_ui": "D047908", "major_topic": false }, { "descriptor": "Models, Biological", "descriptor_ui": "D008954", "major_topic": false }, { "descriptor": "Myosin Light Chains", "descriptor_ui": "D018994", "major_topic": false }, { "descriptor": "Myosin-Light-Chain Phosphatase", "descriptor_ui": "D043263", "major_topic": false }, { "descriptor": "Phospholipases A", "descriptor_ui": "D010741", "major_topic": false }, { "descriptor": "Phospholipases A2", "descriptor_ui": "D054467", "major_topic": false }, { "descriptor": "Phosphorylation", "descriptor_ui": "D010766", "major_topic": false }, { "descriptor": "Protein Serine-Threonine Kinases", "descriptor_ui": "D017346", "major_topic": false }, { "descriptor": "rho GTP-Binding Proteins", "descriptor_ui": "D020741", "major_topic": false }, { "descriptor": "rho-Associated Kinases", "descriptor_ui": "D054460", "major_topic": false }, { "descriptor": "Thrombin", "descriptor_ui": "D013917", "major_topic": false } ], "publication": { "conference_name": null, "date": "2006 Sep", "date_precision": "unknown", "issue": "9", "normalized_date": null, "pages": "1071-1083", "proceedings_title": null, "publisher": "", "title": "Genes to cells : devoted to molecular & cellular mechanisms", "volume": "11", "year": 2006 }, "ssbd": { "database": [], "repository": [] }, "title": "Ca2+ -independent phospholipase A2-dependent sustained Rho-kinase activation exhibits all-or-none response.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "We fabricate scaffolds with a fine linear grating (periodicity of 1 to 8 microm and height of 1 microm) on a glass substrate for controlling cardiomyocyte orientation. The fabrication is done by the solidification of a liquid photopolymerizable material using two laser beam interference. As the photopolymerizable material, we use acrylated trimethylene-carbonate-based oligomers initiated with trimethylolpropane (T/TMP), followed by acrylation at terminal ends. Rat cardiomyocytes cultured on the fabricated scaffolds exhibit cell elongation, orientation, and contraction along the scaffold grating. Fluorescence observation of bundles of actin filaments of the cultured cells show that the cytoskeleton of the cells is also generated and oriented parallel to the grating. With a change in grating periodicity from 8 to 1 microm, the percentage of the cells that show orientation along the grating increase from approximately 40 to 70%. The cell orientation along the grating is observed 18 h after seeding the cells on the scaffold. This result implies that the attachment between a cell and a well-defined microarchitectural substrate at an early stage of culture is a significant determinant of cell morphology.", "classifications": [ { "id": "Fujita", "label": "Group Fujita", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Akiko", "last_name": "Fujita", "name": null }, { "creator_type": "author", "first_name": "Katsumasa", "last_name": "Fujita", "name": null }, { "creator_type": "author", "first_name": "Osamu", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Takehisa", "last_name": "Matsuda", "name": null }, { "creator_type": "author", "first_name": "Satoshi", "last_name": "Kawata", "name": null } ], "identifiers": { "doi": { "normalized": "10.1117/1.2186042" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "16674190" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Animals, Newborn", "descriptor_ui": "D000831", "major_topic": false }, { "descriptor": "Biocompatible Materials", "descriptor_ui": "D001672", "major_topic": false }, { "descriptor": "Cell Culture Techniques", "descriptor_ui": "D018929", "major_topic": false }, { "descriptor": "Cell Polarity", "descriptor_ui": "D016764", "major_topic": false }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Interferometry", "descriptor_ui": "D007368", "major_topic": false }, { "descriptor": "Lasers", "descriptor_ui": "D007834", "major_topic": false }, { "descriptor": "Materials Testing", "descriptor_ui": "D008422", "major_topic": false }, { "descriptor": "Myocytes, Cardiac", "descriptor_ui": "D032383", "major_topic": false }, { "descriptor": "Photochemistry", "descriptor_ui": "D010777", "major_topic": false }, { "descriptor": "Polymers", "descriptor_ui": "D011108", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Rats, Wistar", "descriptor_ui": "D017208", "major_topic": false }, { "descriptor": "Surface Properties", "descriptor_ui": "D013499", "major_topic": false }, { "descriptor": "Tissue Engineering", "descriptor_ui": "D023822", "major_topic": false } ], "publication": { "conference_name": null, "date": "2006 Mar-Apr", "date_precision": "unknown", "issue": "2", "normalized_date": null, "pages": "021015", "proceedings_title": null, "publisher": "", "title": "Journal of biomedical optics", "volume": "11", "year": 2006 }, "ssbd": { "database": [], "repository": [] }, "title": "Control of cardiomyocyte orientation on a microscaffold fabricated by photopolymerization with laser beam interference.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The p53 tumor suppressor plays a major role in maintaining genomic stability. Its activation and stabilization in response to double strand breaks (DSBs) in DNA are regulated primarily by the ATM protein kinase. ATM mediates several posttranslational modifications on p53 itself, as well as phosphorylation of p53's essential inhibitors, Hdm2 and Hdmx. Recently we showed that ATM- and Hdm2-dependent ubiquitination and subsequent degradation of Hdmx following DSB induction are mediated by phosphorylation of Hdmx on S403, S367, and S342, with S403 being targeted directly by ATM. Here we show that S367 phosphorylation is mediated by the Chk2 protein kinase, a downstream kinase of ATM. This phosphorylation, which is important for subsequent Hdmx ubiquitination and degradation, creates a binding site for 14-3-3 proteins which controls nuclear accumulation of Hdmx following DSBs. Phosphorylation of S342 also contributed to optimal 14-3-3 interaction and nuclear accumulation of Hdmx, but phosphorylation of S403 did not. Our data indicate that binding of a 14-3-3 dimer and subsequent nuclear accumulation are essential steps toward degradation of p53's inhibitor, Hdmx, in response to DNA damage. These results demonstrate a sophisticated control by ATM of a target protein, Hdmx, which itself is one of several ATM targets in the ATM-p53 axis of the DNA damage response.", "classifications": [ { "id": "Okamoto", "label": "Group Okamoto", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yaron", "last_name": "Pereg", "name": null }, { "creator_type": "author", "first_name": "Suzanne", "last_name": "Lam", "name": null }, { "creator_type": "author", "first_name": "Amina", "last_name": "Teunisse", "name": null }, { "creator_type": "author", "first_name": "Sharon", "last_name": "Biton", "name": null }, { "creator_type": "author", "first_name": "Erik", "last_name": "Meulmeester", "name": null }, { "creator_type": "author", "first_name": "Leonid", "last_name": "Mittelman", "name": null }, { "creator_type": "author", "first_name": "Giacomo", "last_name": "Buscemi", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Okamoto", "name": null }, { "creator_type": "author", "first_name": "Yoichi", "last_name": "Taya", "name": null }, { "creator_type": "author", "first_name": "Yosef", "last_name": "Shiloh", "name": null }, { "creator_type": "author", "first_name": "Aart G.", "last_name": "Jochemsen", "name": null } ], "identifiers": { "doi": { "normalized": "10.1128/mcb.00562-06" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "16943424" } }, "mesh": [ { "descriptor": "14-3-3 Proteins", "descriptor_ui": "D048948", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Ataxia Telangiectasia Mutated Proteins", "descriptor_ui": "D064007", "major_topic": false }, { "descriptor": "Cell Cycle Proteins", "descriptor_ui": "D018797", "major_topic": false }, { "descriptor": "Cell Nucleus", "descriptor_ui": "D002467", "major_topic": false }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Checkpoint Kinase 2", "descriptor_ui": "D064447", "major_topic": false }, { "descriptor": "DNA Damage", "descriptor_ui": "D004249", "major_topic": false }, { "descriptor": "DNA-Binding Proteins", "descriptor_ui": "D004268", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Models, Biological", "descriptor_ui": "D008954", "major_topic": false }, { "descriptor": "Nuclear Proteins", "descriptor_ui": "D009687", "major_topic": false }, { "descriptor": "Phosphorylation", "descriptor_ui": "D010766", "major_topic": false }, { "descriptor": "Phosphoserine", "descriptor_ui": "D010768", "major_topic": false }, { "descriptor": "Protein Binding", "descriptor_ui": "D011485", "major_topic": false }, { "descriptor": "Protein Processing, Post-Translational", "descriptor_ui": "D011499", "major_topic": false }, { "descriptor": "Protein Serine-Threonine Kinases", "descriptor_ui": "D017346", "major_topic": false }, { "descriptor": "Proto-Oncogene Proteins", "descriptor_ui": "D011518", "major_topic": false }, { "descriptor": "Tumor Suppressor Proteins", "descriptor_ui": "D025521", "major_topic": false } ], "publication": { "conference_name": null, "date": "2006 Sep", "date_precision": "unknown", "issue": "18", "normalized_date": null, "pages": "6819-6831", "proceedings_title": null, "publisher": "", "title": "Molecular and Cellular Biology", "volume": "26", "year": 2006 }, "ssbd": { "database": [], "repository": [] }, "title": "Differential Roles of ATM- and Chk2-Mediated Phosphorylations of Hdmx in Response to DNA Damage†.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Some immortal cells use the alternative lengthening of telomeres (ALT) pathway to maintain their telomeres instead of telomerase. Previous studies revealed that homologous recombination (HR) contributes to the ALT pathway. To further elucidate molecular mechanisms, we inactivated Rad54 involved in HR, in mouse ALT embryonic stem (ES) cells. Although Rad54-deficient ALT ES cells showed radiosensitivity in line with expectation, cell growth and telomeres were maintained for more than 200 cell divisions. Furthermore, although MMC-stimulated sister chromatid exchange (SCE) was suppressed in the Rad54-deficient ALT ES cells, ALT-associated telomere SCE was not affected. This is the first genetic evidence that mouse Rad54 is dispensable for the ALT pathway.", "classifications": [ { "id": "Yusa", "label": "Group Yusa", "parent": "Eiraku", "type": "group" }, { "id": "Eiraku", "label": "Team Eiraku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Koichi", "last_name": "Akiyama", "name": null }, { "creator_type": "author", "first_name": "Kosuke", "last_name": "Yusa", "name": null }, { "creator_type": "author", "first_name": "Hideharu", "last_name": "Hashimoto", "name": null }, { "creator_type": "author", "first_name": "Anuradha", "last_name": "Poonepalli", "name": null }, { "creator_type": "author", "first_name": "Manoor Prakash", "last_name": "Hande", "name": null }, { "creator_type": "author", "first_name": "Naoki", "last_name": "Kakazu", "name": null }, { "creator_type": "author", "first_name": "Junji", "last_name": "Takeda", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Tachibana", "name": null }, { "creator_type": "author", "first_name": "Yoichi", "last_name": "Shinkai", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/j.1365-2443.2006.01020.x" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "17054727" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "DNA Helicases", "descriptor_ui": "D004265", "major_topic": false }, { "descriptor": "Embryonic Stem Cells", "descriptor_ui": "D053595", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Nuclear Proteins", "descriptor_ui": "D009687", "major_topic": false }, { "descriptor": "Recombination, Genetic", "descriptor_ui": "D011995", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Sister Chromatid Exchange", "descriptor_ui": "D012854", "major_topic": false }, { "descriptor": "Telomere", "descriptor_ui": "D016615", "major_topic": false } ], "publication": { "conference_name": null, "date": "2006 Nov", "date_precision": "unknown", "issue": "11", "normalized_date": null, "pages": "1305-1315", "proceedings_title": null, "publisher": "", "title": "Genes to cells : devoted to molecular & cellular mechanisms", "volume": "11", "year": 2006 }, "ssbd": { "database": [], "repository": [] }, "title": "Rad54 is dispensable for the ALT pathway.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The synaptic organization between and among the insular cortex (IC) axons, central amygdaloid nucleus (ACe) axons and posterolateral hypothalamus (PLH) neurons was investigated in the rat using double anterograde tracing and anterograde tracing combined with postembedding immunogold analysis. After ipsilateral injections of biotinylated dextran amine (BDA) into the IC and Phaseolus vulgaris-leucoagglutinin (PHA-L) into the ACe, the conspicuous overlapping distribution of BDA-labeled axon terminals and PHA-L-labeled axon terminals was found in the PLH region just medial to the subthalamic nucleus ipsilateral to the injection sites. At the electron microscopic level, approximately two-thirds of the IC terminals made synapses with small-sized dendrites and the rest did with dendritic spines of the PLH neurons, whereas about 79%, 16% and 5% of the ACe terminals established synapses with small- to medium-sized dendrites, somata, and dendritic spines, respectively, of the PLH neurons. In addition, the IC axon terminals contained densely packed round clear vesicles and their synapses were of asymmetrical type. On the other hand, most of the ACe terminals contained not only pleomorphic clear vesicles but also dense-cored vesicles and their synapses were of symmetrical type although some ACe terminals contained densely packed round clear vesicles and formed asymmetrical synapses. Most of the postsynaptic elements received synaptic inputs from the IC or ACe terminals, and some of single postsynaptic elements received convergent synaptic inputs from both sets of terminals. Furthermore, almost all the ACe terminals were revealed to be immunoreactive for gamma-aminobutyric acid (GABA), by using the anterograde BDA tracing technique combined with immunohistochemistry for GABA. The present data suggest that single PLH neurons are under the excitatory influence of the IC and/or inhibitory influence of the ACe in the circuitry involved in the regulation of cardiovascular functions.", "classifications": [ { "id": "Yokota", "label": "Group Yokota", "parent": "Enomoto", "type": "group" }, { "id": "Enomoto", "label": "Team Enomoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Toshiko", "last_name": "Tsumori", "name": null }, { "creator_type": "author", "first_name": "Shigefumi", "last_name": "Yokota", "name": null }, { "creator_type": "author", "first_name": "Yi", "last_name": "Qin", "name": null }, { "creator_type": "author", "first_name": "Tatsuro", "last_name": "Oka", "name": null }, { "creator_type": "author", "first_name": "Yukihiko", "last_name": "Yasui", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.neures.2006.07.005" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "16935375" } }, "mesh": [ { "descriptor": "Amygdala", "descriptor_ui": "D000679", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Biotin", "descriptor_ui": "D001710", "major_topic": false }, { "descriptor": "Brain Mapping", "descriptor_ui": "D001931", "major_topic": false }, { "descriptor": "Cerebral Cortex", "descriptor_ui": "D002540", "major_topic": false }, { "descriptor": "Dextrans", "descriptor_ui": "D003911", "major_topic": false }, { "descriptor": "gamma-Aminobutyric Acid", "descriptor_ui": "D005680", "major_topic": false }, { "descriptor": "Hypothalamic Area, Lateral", "descriptor_ui": "D007026", "major_topic": false }, { "descriptor": "Immunohistochemistry", "descriptor_ui": "D007150", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Microscopy, Electron, Transmission", "descriptor_ui": "D046529", "major_topic": false }, { "descriptor": "Neural Pathways", "descriptor_ui": "D009434", "major_topic": false }, { "descriptor": "Phytohemagglutinins", "descriptor_ui": "D010835", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Rats, Wistar", "descriptor_ui": "D017208", "major_topic": false }, { "descriptor": "Synapses", "descriptor_ui": "D013569", "major_topic": false } ], "publication": { "conference_name": null, "date": "2006 Nov", "date_precision": "unknown", "issue": "3", "normalized_date": null, "pages": "261-269", "proceedings_title": null, "publisher": "", "title": "Neuroscience research", "volume": "56", "year": 2006 }, "ssbd": { "database": [], "repository": [] }, "title": "A light and electron microscopic analysis of the convergent insular cortical and amygdaloid projections to the posterior lateral hypothalamus in the rat, with special reference to cardiovascular function.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Calcium ions (Ca(2+)) are particularly important in cellular homeostasis and activity. To elicit physiologically relevant timing and spatial patterns of Ca(2+) signaling, ion channels in the surface of each cell precisely control Ca(2+) influx across the plasma membrane. A group of surface membrane ion channels called receptor-activated cation/Ca(2+) channels (RACCs) are activated by diverse cellular stimuli from the surrounding extracellular environment via receptors and other pathways such as heat, osmotic pressure, and mechanical and oxidative stress. An important clue to understanding the molecular mechanisms underlying the functional diversity of RACCs was first attained by molecular identification of the transient receptor potential (trp) protein (TRP), which mediates light-induced depolarization in Drosophila photoreceptor cells, and its homologues from various biological species. Recent studies have revealed that respective TRP channels are indeed activated by characteristic cellular stimuli. Furthermore, the involvement of TRP channels has been demonstrated in the signaling pathways essential for tissue-specific functions as well as ubiquitous biological responses, such as cell proliferation, differentiation, and death. These findings encourage the usage of TRP channels and their signalplexes as powerful tools for developing novel pharmaceutical targets.", "classifications": [ { "id": "Nishida", "label": "Group Nishida", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Motohiro", "last_name": "Nishida", "name": null }, { "creator_type": "author", "first_name": "Yuji", "last_name": "Hara", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Ryuji", "last_name": "Inoue", "name": null }, { "creator_type": "author", "first_name": "Yasuo", "last_name": "Mori", "name": null } ], "identifiers": { "doi": { "normalized": "10.1080/10739680600885111" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "16990213" } }, "mesh": [ { "descriptor": "Amino Acid Sequence", "descriptor_ui": "D000595", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Calcium Channels", "descriptor_ui": "D015220", "major_topic": false }, { "descriptor": "Calcium Signaling", "descriptor_ui": "D020013", "major_topic": false }, { "descriptor": "Cell Cycle", "descriptor_ui": "D002453", "major_topic": false }, { "descriptor": "Cell Proliferation", "descriptor_ui": "D049109", "major_topic": false }, { "descriptor": "Cloning, Molecular", "descriptor_ui": "D003001", "major_topic": false }, { "descriptor": "Drosophila", "descriptor_ui": "D004330", "major_topic": false }, { "descriptor": "Drosophila Proteins", "descriptor_ui": "D029721", "major_topic": false }, { "descriptor": "Genetic Variation", "descriptor_ui": "D014644", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Models, Biological", "descriptor_ui": "D008954", "major_topic": false }, { "descriptor": "Models, Molecular", "descriptor_ui": "D008958", "major_topic": false }, { "descriptor": "Molecular Sequence Data", "descriptor_ui": "D008969", "major_topic": false }, { "descriptor": "Muscle, Smooth, Vascular", "descriptor_ui": "D009131", "major_topic": false }, { "descriptor": "Oxidation-Reduction", "descriptor_ui": "D010084", "major_topic": false }, { "descriptor": "Phylogeny", "descriptor_ui": "D010802", "major_topic": false }, { "descriptor": "Sequence Homology, Amino Acid", "descriptor_ui": "D017386", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Transient Receptor Potential Channels", "descriptor_ui": "D050051", "major_topic": false }, { "descriptor": "Type C Phospholipases", "descriptor_ui": "D010738", "major_topic": false }, { "descriptor": "Vasoconstriction", "descriptor_ui": "D014661", "major_topic": false } ], "publication": { "conference_name": null, "date": "2006 Oct-Nov", "date_precision": "unknown", "issue": "7", "normalized_date": null, "pages": "535-550", "proceedings_title": null, "publisher": "", "title": "Microcirculation (New York, N.Y. : 1994)", "volume": "13", "year": 2006 }, "ssbd": { "database": [], "repository": [] }, "title": "TRP channels: molecular diversity and physiological function.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Aldosterone has been demonstrated to play an important role in the pathogenesis of various cardiovascular diseases. Vascular structural remodeling, including vascular smooth muscle cell (VSMC) proliferation, has been also reported in small resistance arteries of patients with primary aldosteronism. Therefore, in this study, we examined whether genes involved in the regulation of the cell cycle were induced by aldosterone alone in cultured human VSMCs and in human small resistance arteries. Results of these studies eventually demonstrated that MDM2, one of the genes involved in anti-apoptosis and cell growth, was markedly increased in mineralocorticoid receptor (MR)-positive VSMCs by aldosterone in all microarray, reverse transcriptase-polymerase chain reaction, immunoblotting, and immunofluorescence analyses. In addition, an analysis using small interfering RNA demonstrated that this gene product was involved in cell proliferation of VSMCs induced by aldosterone. Eplerenone, a specific MR antagonist, inhibited this gene induction by aldosterone in VSMCs. MDM2 protein was also more abundant in VSMCs of small resistance arteries in patients with primary aldosteronism compared with a control population. MDM2 is therefore considered one of the mineralocorticoid-responsive genes that regulates cell proliferation of VSMCs induced by MR-mediated aldosterone stimulation, possibly playing an important role in aldosterone-induced vascular structural remodeling.", "classifications": [ { "id": "Suzuki", "label": "Group Suzuki", "parent": "Takekawa", "type": "group" }, { "id": "Takekawa", "label": "Team Takekawa", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yasuhiro", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Saya", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Katsuhiko", "last_name": "Ono", "name": null }, { "creator_type": "author", "first_name": "Ikumi", "last_name": "Miura", "name": null }, { "creator_type": "author", "first_name": "Fumitoshi", "last_name": "Satoh", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Moriya", "name": null }, { "creator_type": "author", "first_name": "Haruo", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Shogo", "last_name": "Yamada", "name": null }, { "creator_type": "author", "first_name": "Sadayoshi", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Hironobu", "last_name": "Sasano", "name": null } ], "identifiers": { "doi": { "normalized": "10.2353/ajpath.2006.051351" }, "pmcid": { "normalized": "PMC1698800" }, "pmid": { "normalized": "16877339" } }, "mesh": [ { "descriptor": "Aldosterone", "descriptor_ui": "D000450", "major_topic": false }, { "descriptor": "Arteries", "descriptor_ui": "D001158", "major_topic": false }, { "descriptor": "Cell Proliferation", "descriptor_ui": "D049109", "major_topic": false }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Fluorescent Antibody Technique", "descriptor_ui": "D005455", "major_topic": false }, { "descriptor": "Gene Expression Regulation", "descriptor_ui": "D005786", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Microarray Analysis", "descriptor_ui": "D046228", "major_topic": false }, { "descriptor": "Mineralocorticoids", "descriptor_ui": "D008901", "major_topic": false }, { "descriptor": "Muscle, Smooth, Vascular", "descriptor_ui": "D009131", "major_topic": false }, { "descriptor": "Proto-Oncogene Proteins c-mdm2", "descriptor_ui": "D051736", "major_topic": false }, { "descriptor": "Receptors, Mineralocorticoid", "descriptor_ui": "D018161", "major_topic": false }, { "descriptor": "Reverse Transcriptase Polymerase Chain Reaction", "descriptor_ui": "D020133", "major_topic": false }, { "descriptor": "RNA, Messenger", "descriptor_ui": "D012333", "major_topic": false }, { "descriptor": "RNA, Small Interfering", "descriptor_ui": "D034741", "major_topic": false }, { "descriptor": "Transcriptional Activation", "descriptor_ui": "D015533", "major_topic": false }, { "descriptor": "Transfection", "descriptor_ui": "D014162", "major_topic": false } ], "publication": { "conference_name": null, "date": "2006 Aug", "date_precision": "unknown", "issue": "2", "normalized_date": null, "pages": "362-371", "proceedings_title": null, "publisher": "", "title": "The American journal of pathology", "volume": "169", "year": 2006 }, "ssbd": { "database": [], "repository": [] }, "title": "MDM2: a novel mineralocorticoid-responsive gene involved in aldosterone-induced human vascular structural remodeling.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Genetic interactions provide information about genes and processes with overlapping functions in biological systems. For Saccharomyces cerevisiae, computational integration of multiple types of functional genomic data is used to generate genome-wide predictions of genetic interactions. However, this methodology cannot be applied to the vastly more complex genome of metazoans, and only recently has the first metazoan genome-wide prediction of genetic interactions been reported. The prediction for Caenorhabditis elegans was generated by computationally integrating functional genomic data from S. cerevisiae, C. elegans and Drosophila melanogaster. This achievement is an important step toward system-level understanding of biological systems and human diseases.", "classifications": [ { "id": "Onami", "label": "Group Onami", "parent": "Fujiwara", "type": "group" }, { "id": "Fujiwara", "label": "Team Fujiwara", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Shuichi", "last_name": "Onami", "name": null }, { "creator_type": "author", "first_name": "Hiroaki", "last_name": "Kitano", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/bies.20490" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "17041895" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Computational Biology", "descriptor_ui": "D019295", "major_topic": false }, { "descriptor": "Genome, Helminth", "descriptor_ui": "D049751", "major_topic": false }, { "descriptor": "Genomics", "descriptor_ui": "D023281", "major_topic": true }, { "descriptor": "Helminth Proteins", "descriptor_ui": "D015801", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Models, Genetic", "descriptor_ui": "D008957", "major_topic": false } ], "publication": { "conference_name": null, "date": "2006 Nov", "date_precision": "unknown", "issue": "11", "normalized_date": null, "pages": "1087-1090", "proceedings_title": null, "publisher": "", "title": "BioEssays : news and reviews in molecular, cellular and developmental biology", "volume": "28", "year": 2006 }, "ssbd": { "database": [], "repository": [] }, "title": "Genome-wide prediction of genetic interactions in a metazoan.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Overexpression of constitutively active (CA)-G alpha13 significantly increased the expression of interleukin (IL)-1beta and IL-6 mRNAs and proteins in rat cardiac fibroblasts. IL-1beta mRNA induction by CA-G alpha13 was suppressed by diphenyleneiodonium (DPI), an NADPH oxidase inhibitor, but not by BAPTA-AM, an intracellular Ca2+ chelator. In contrast, IL-6 mRNA induction by CA-G alpha13 was suppressed by BAPTA-AM but not by DPI. However, both IL-1beta and IL-6 mRNA induction was suppressed by nuclear factor kappaB (NF-kappaB) inhibitors. The CA-G alpha13-induced NF-kappaB activation was suppressed by DPI and BAPTA-AM, but not C3 toxin and the Rho-kinase inhibitor Y27632. IL-6 mRNA induction by CA-G alpha13 was suppressed by SK&F96365 (1-[beta-[3-(4-methoxyphenyl)propoxy]-4-methoxyphenethyl]-1H-imidazole hydrochloride), an inhibitor of receptor-activated nonselective cation channels, and the expression of CA-G alpha13 increased basal Ca2+ influx. These results suggest that G alpha13 regulates IL-1beta mRNA induction through the reactive oxygen species-NF-kappaB pathway, while it regulates IL-6 mRNA induction through the Ca2+-NF-kappaB pathway.", "classifications": [ { "id": "Nishida", "label": "Group Nishida", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yuichi", "last_name": "Nagamatsu", "name": null }, { "creator_type": "author", "first_name": "Motohiro", "last_name": "Nishida", "name": null }, { "creator_type": "author", "first_name": "Naoya", "last_name": "Onohara", "name": null }, { "creator_type": "author", "first_name": "Masashi", "last_name": "Fukutomi", "name": null }, { "creator_type": "author", "first_name": "Yoshiko", "last_name": "Maruyama", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Yoji", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Kurose", "name": null } ], "identifiers": { "doi": { "normalized": "10.1254/jphs.fp0051036" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "16778360" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Calcium", "descriptor_ui": "D002118", "major_topic": false }, { "descriptor": "Cytokines", "descriptor_ui": "D016207", "major_topic": false }, { "descriptor": "Egtazic Acid", "descriptor_ui": "D004533", "major_topic": false }, { "descriptor": "Fibroblasts", "descriptor_ui": "D005347", "major_topic": false }, { "descriptor": "GTP-Binding Protein alpha Subunits, G12-G13", "descriptor_ui": "D044365", "major_topic": false }, { "descriptor": "Heart Ventricles", "descriptor_ui": "D006352", "major_topic": false }, { "descriptor": "Interleukin-1", "descriptor_ui": "D007375", "major_topic": false }, { "descriptor": "Interleukin-6", "descriptor_ui": "D015850", "major_topic": false }, { "descriptor": "NF-kappa B", "descriptor_ui": "D016328", "major_topic": false }, { "descriptor": "Onium Compounds", "descriptor_ui": "D009861", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Rats, Sprague-Dawley", "descriptor_ui": "D017207", "major_topic": false }, { "descriptor": "Reactive Oxygen Species", "descriptor_ui": "D017382", "major_topic": false }, { "descriptor": "RNA, Messenger", "descriptor_ui": "D012333", "major_topic": false } ], "publication": { "conference_name": null, "date": "2006 Jun", "date_precision": "unknown", "issue": "2", "normalized_date": null, "pages": "144-150", "proceedings_title": null, "publisher": "", "title": "Journal of pharmacological sciences", "volume": "101", "year": 2006 }, "ssbd": { "database": [], "repository": [] }, "title": "Heterotrimeric G protein G alpha13-induced induction of cytokine mRNAs through two distinct pathways in cardiac fibroblasts.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Tissue inhibitor of metalloproteinase-3 (Timp-3), an inhibitor of matrix-degrading enzymes, is an important molecule for maintenance of the extracellular matrix. In this study, we generated Timp-3-deficient mice and used them to examine the effect of Timp-3-deficiency on blood pressure and to investigate the role of Timp-3 in the kidney following unilateral ureteral obstruction. The blood pressure and heart rate of Timp-3-deficient mice were not significantly different from those of wild-type mice. On the other hand, the obstructed kidneys of Timp-3-deficient mice developed more severe hydronephrosis than those of wild-type animals. Matrix metalloproteinase activities assessed by in situ zymography and transforming growth factor-beta expression were elevated in Timp-3-deficient mice. The renal tissues were thinner and the ratio of renal medulla to cortex was significantly lower in the obstructed Timp-3-deficient kidneys. These findings indicate that Timp-3-deficiency does not substantially affect the blood pressure in mice, and that Timp-3 plays an important role in the maintenance of renal macrostructure after unilateral ureteral obstruction.", "classifications": [ { "id": "Suzuki", "label": "Group Suzuki", "parent": "Takekawa", "type": "group" }, { "id": "Takekawa", "label": "Team Takekawa", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Hidenobu", "last_name": "Kawamoto", "name": null }, { "creator_type": "author", "first_name": "Osamu", "last_name": "Yasuda", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Tohru", "last_name": "Ozaki", "name": null }, { "creator_type": "author", "first_name": "Takamori", "last_name": "Yotsui", "name": null }, { "creator_type": "author", "first_name": "Masayoshi", "last_name": "Higuchi", "name": null }, { "creator_type": "author", "first_name": "Hiromi", "last_name": "Rakugi", "name": null }, { "creator_type": "author", "first_name": "Keisuke", "last_name": "Fukuo", "name": null }, { "creator_type": "author", "first_name": "Toshio", "last_name": "Ogihara", "name": null }, { "creator_type": "author", "first_name": "Nobuyo", "last_name": "Maeda", "name": null } ], "identifiers": { "doi": { "normalized": "10.1291/hypres.29.285" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "16778336" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Blood Pressure", "descriptor_ui": "D001794", "major_topic": false }, { "descriptor": "Extracellular Matrix", "descriptor_ui": "D005109", "major_topic": false }, { "descriptor": "Heart Rate", "descriptor_ui": "D006339", "major_topic": false }, { "descriptor": "Hydronephrosis", "descriptor_ui": "D006869", "major_topic": false }, { "descriptor": "Kidney Cortex", "descriptor_ui": "D007672", "major_topic": false }, { "descriptor": "Kidney Medulla", "descriptor_ui": "D007679", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Tissue Inhibitor of Metalloproteinase-3", "descriptor_ui": "D019717", "major_topic": false }, { "descriptor": "Transforming Growth Factor beta", "descriptor_ui": "D016212", "major_topic": false }, { "descriptor": "Ureteral Obstruction", "descriptor_ui": "D014517", "major_topic": false } ], "publication": { "conference_name": null, "date": "2006 Apr", "date_precision": "unknown", "issue": "4", "normalized_date": null, "pages": "285-294", "proceedings_title": null, "publisher": "", "title": "Hypertension research : official journal of the Japanese Society of Hypertension", "volume": "29", "year": 2006 }, "ssbd": { "database": [], "repository": [] }, "title": "Tissue inhibitor of metalloproteinase-3 plays important roles in the kidney following unilateral ureteral obstruction.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The search for novel enzymes is an important but difficult task in functional genomics. Here, we present a systematic method based on in vitro assays in combination with metabolite profiling to discover novel enzymatic activities. A complex mixture of metabolites is incubated with purified candidate proteins and the reaction mixture is subsequently profiled by capillary electrophoresis electrospray ionization mass spectrometry (CE-MS). Specific changes in the metabolite composition can directly suggest the presence of an enzymatic activity while subsequent identification of the compounds whose level changed specifically can pinpoint the actual substrate(s) and product(s) of the reaction. We first evaluated the method using several Escherichia coli metabolic enzymes and then applied it to the functional screening of uncharacterized proteins. In this manner, YbhA and YbiV proteins were found to display both phosphotransferase and phosphatase activity toward different sugars/sugar phosphates. Our approach should be broadly applicable and useful for enzyme discovery in any system.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Natsumi", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Martin", "last_name": "Robert", "name": null }, { "creator_type": "author", "first_name": "Sayaka", "last_name": "Kitamura", "name": null }, { "creator_type": "author", "first_name": "Richard", "last_name": "Baran", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Hirotada", "last_name": "Mori", "name": null }, { "creator_type": "author", "first_name": "Takaaki", "last_name": "Nishioka", "name": null }, { "creator_type": "author", "first_name": "Masaru", "last_name": "Tomita", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/pr0600576" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "16889420" } }, "mesh": [ { "descriptor": "Electrophoresis, Capillary", "descriptor_ui": "D019075", "major_topic": false }, { "descriptor": "Enzymes", "descriptor_ui": "D004798", "major_topic": false }, { "descriptor": "Escherichia coli", "descriptor_ui": "D004926", "major_topic": false }, { "descriptor": "Escherichia coli Proteins", "descriptor_ui": "D029968", "major_topic": false }, { "descriptor": "Phosphoprotein Phosphatases", "descriptor_ui": "D010749", "major_topic": false }, { "descriptor": "Recombinant Proteins", "descriptor_ui": "D011994", "major_topic": false }, { "descriptor": "Reproducibility of Results", "descriptor_ui": "D015203", "major_topic": false }, { "descriptor": "Spectrometry, Mass, Electrospray Ionization", "descriptor_ui": "D021241", "major_topic": false } ], "publication": { "conference_name": null, "date": "2006 Aug", "date_precision": "unknown", "issue": "8", "normalized_date": null, "pages": "1979-1987", "proceedings_title": null, "publisher": "", "title": "Journal of proteome research", "volume": "5", "year": 2006 }, "ssbd": { "database": [], "repository": [] }, "title": "Metabolomics approach for enzyme discovery.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The extracellular-signal-regulated kinase (ERK) mitogen-activated protein (MAP) kinase signaling pathway plays an important role in various cellular responses, including cell proliferation, cell differentiation and cell survival. Recent studies have identified a number of Ras/ERK signaling-related proteins, such as scaffold proteins and inhibitors. These proteins modulate ERK signaling and thereby could give variations in ERK signaling outputs that regulate cell fate decisions. Here we focus on the role of ERK signaling in cell cycle progression from G0/G1 to S phase and cancer.", "classifications": [ { "id": "Yamamoto", "label": "Group Yamamoto", "parent": "Toyoshima", "type": "group" }, { "id": "Toyoshima", "label": "Team Toyoshima", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Satoru", "last_name": "Torii", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Yoshiki", "last_name": "Tsuchiya", "name": null }, { "creator_type": "author", "first_name": "Eisuke", "last_name": "Nishida", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/j.1349-7006.2006.00244.x" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "16800820" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Transformation, Neoplastic", "descriptor_ui": "D002471", "major_topic": false }, { "descriptor": "Disease Progression", "descriptor_ui": "D018450", "major_topic": false }, { "descriptor": "Extracellular Signal-Regulated MAP Kinases", "descriptor_ui": "D048049", "major_topic": false }, { "descriptor": "G1 Phase", "descriptor_ui": "D016193", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Neoplasms", "descriptor_ui": "D009369", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false } ], "publication": { "conference_name": null, "date": "2006 Aug", "date_precision": "unknown", "issue": "8", "normalized_date": null, "pages": "697-702", "proceedings_title": null, "publisher": "", "title": "Cancer science", "volume": "97", "year": 2006 }, "ssbd": { "database": [], "repository": [] }, "title": "ERK MAP kinase in G cell cycle progression and cancer.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The Sleeping Beauty (SB) transposon system has generated many transposon-insertional mutant mouse lines, some of which have resulted in embryonic lethality when bred to homozygosity. Here we report one such insertion mapped to the mouse actin-related protein complex subunit 3 gene (Arpc3). Arpc3 is a component of the Arp2/3 complex, which plays a major role in actin nucleation with Y-shaped branching from the mother actin filament in response to migration signaling. Arpc3 transposon-inserted mutants developed only to the blastocyst stage. In vitro blastocyst culture of Arpc3 mutants exhibited severe spreading impairment of trophoblasts. This phenotype was also observed in compound heterozygotes generated using conventional gene-targeted and transposon-inserted alleles. Arpc3-deficient mutants were shown to lack actin-rich structures in the spreading trophoblast. Electron microscopic analysis demonstrated the lack of mesh-like structures at the cell periphery, suggesting a role of Arpc3 in Y-shaped branching formation. These data indicate the importance of Arpc3 in the Arp2/3 complex for trophoblast outgrowth and suggest that Arpc3 may be indispensable for implantation.", "classifications": [ { "id": "Yusa", "label": "Group Yusa", "parent": "Eiraku", "type": "group" }, { "id": "Eiraku", "label": "Team Eiraku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Kojiro", "last_name": "Yae", "name": null }, { "creator_type": "author", "first_name": "Vincent W.", "last_name": "Keng", "name": null }, { "creator_type": "author", "first_name": "Masato", "last_name": "Koike", "name": null }, { "creator_type": "author", "first_name": "Kosuke", "last_name": "Yusa", "name": null }, { "creator_type": "author", "first_name": "Michiyoshi", "last_name": "Kouno", "name": null }, { "creator_type": "author", "first_name": "Yoshihiro", "last_name": "Uno", "name": null }, { "creator_type": "author", "first_name": "Gen", "last_name": "Kondoh", "name": null }, { "creator_type": "author", "first_name": "Takahiro", "last_name": "Gotow", "name": null }, { "creator_type": "author", "first_name": "Yasuo", "last_name": "Uchiyama", "name": null }, { "creator_type": "author", "first_name": "Kyoji", "last_name": "Horie", "name": null }, { "creator_type": "author", "first_name": "Junji", "last_name": "Takeda", "name": null } ], "identifiers": { "doi": { "normalized": "10.1128/mcb.00018-06" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "16880528" } }, "mesh": [ { "descriptor": "Actin-Related Protein 2-3 Complex", "descriptor_ui": "D051376", "major_topic": false }, { "descriptor": "Actins", "descriptor_ui": "D000199", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Chromosomes, Mammalian", "descriptor_ui": "D033481", "major_topic": false }, { "descriptor": "Cytoskeleton", "descriptor_ui": "D003599", "major_topic": false }, { "descriptor": "DNA Transposable Elements", "descriptor_ui": "D004251", "major_topic": false }, { "descriptor": "Genetic Complementation Test", "descriptor_ui": "D005816", "major_topic": false }, { "descriptor": "Introns", "descriptor_ui": "D007438", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "Mutagenesis, Insertional", "descriptor_ui": "D016254", "major_topic": false }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": false }, { "descriptor": "Phenotype", "descriptor_ui": "D010641", "major_topic": true }, { "descriptor": "Transposases", "descriptor_ui": "D019895", "major_topic": false }, { "descriptor": "Trophoblasts", "descriptor_ui": "D014327", "major_topic": false } ], "publication": { "conference_name": null, "date": "2006 Aug", "date_precision": "unknown", "issue": "16", "normalized_date": null, "pages": "6185-6196", "proceedings_title": null, "publisher": "", "title": "Molecular and Cellular Biology", "volume": "26", "year": 2006 }, "ssbd": { "database": [], "repository": [] }, "title": "Sleeping Beauty Transposon-Based Phenotypic Analysis of Mice: Lack of Arpc3 Results in Defective Trophoblast Outgrowth.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Neural stem cells are known to give rise to distinct subtypes of neurons and glial cells over time by changing their competency. However, precise characterization of neural stem cells at various developmental stages remains to be performed. For such analysis, a tool to manipulate neural stem cells at different time points is necessary. Here, we generated transgenic mice that express Cre-ER(T2) in the ventricular zone of the developing nervous system under the control of the nestin promoter and enhancer (Nes-CreER(T2)). In mice expressing Cre-ER(T2) at appropriate levels, Cre recombinase activity was mostly inactive but efficiently activated by tamoxifen within 1 day. When such mice were crossed with the ROSA-26 or Z/EG reporter mice, neural stem cells were permanently labeled after administration of tamoxifen. Thus, Nes-CreER(T2) mice offer a powerful tool to manipulate neural stem cells genetically at desired time points.", "classifications": [ { "id": "Imayoshi", "label": "Group Imayoshi", "parent": "Imayoshi", "type": "group" }, { "id": "Imayoshi", "label": "Team Imayoshi", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Itaru", "last_name": "Imayoshi", "name": null }, { "creator_type": "author", "first_name": "Toshiyuki", "last_name": "Ohtsuka", "name": null }, { "creator_type": "author", "first_name": "Daniel", "last_name": "Metzger", "name": null }, { "creator_type": "author", "first_name": "Pierre", "last_name": "Chambon", "name": null }, { "creator_type": "author", "first_name": "Ryoichiro", "last_name": "Kageyama", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/dvg.20212" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "16652364" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Brain", "descriptor_ui": "D001921", "major_topic": false }, { "descriptor": "Crosses, Genetic", "descriptor_ui": "D003433", "major_topic": false }, { "descriptor": "Enhancer Elements, Genetic", "descriptor_ui": "D004742", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Gene Dosage", "descriptor_ui": "D018628", "major_topic": false }, { "descriptor": "Gene Expression Regulation, Developmental", "descriptor_ui": "D018507", "major_topic": true }, { "descriptor": "Gene Targeting", "descriptor_ui": "D018390", "major_topic": false }, { "descriptor": "Genes, Reporter", "descriptor_ui": "D017930", "major_topic": false }, { "descriptor": "Integrases", "descriptor_ui": "D019426", "major_topic": false }, { "descriptor": "Intermediate Filament Proteins", "descriptor_ui": "D007381", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Transgenic", "descriptor_ui": "D008822", "major_topic": false }, { "descriptor": "Nerve Tissue Proteins", "descriptor_ui": "D009419", "major_topic": false }, { "descriptor": "Nervous System", "descriptor_ui": "D009420", "major_topic": true }, { "descriptor": "Nestin", "descriptor_ui": "D064231", "major_topic": false }, { "descriptor": "Pregnancy", "descriptor_ui": "D011247", "major_topic": false }, { "descriptor": "Promoter Regions, Genetic", "descriptor_ui": "D011401", "major_topic": false }, { "descriptor": "Proteins", "descriptor_ui": "D011506", "major_topic": false }, { "descriptor": "RNA, Untranslated", "descriptor_ui": "D022661", "major_topic": false }, { "descriptor": "Stem Cells", "descriptor_ui": "D013234", "major_topic": true }, { "descriptor": "Tamoxifen", "descriptor_ui": "D013629", "major_topic": false } ], "publication": { "conference_name": null, "date": "2006 May", "date_precision": "unknown", "issue": "5", "normalized_date": null, "pages": "233-238", "proceedings_title": null, "publisher": "", "title": "Genesis (New York, N.Y. : 2000)", "volume": "44", "year": 2006 }, "ssbd": { "database": [], "repository": [] }, "title": "Temporal regulation of Cre recombinase activity in neural stem cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The purpose of this study was to develop a method of kinetic analysis for picture archiving and communication system (PACS) management and computer-aided diagnostic application in dynamic chest radiography. The main analytical technique used in this study was a new algorithm that converts dynamic radiographs into a color-static image. The algorithm is a visualization technique for kinetic information that uses the intensity-density transformation and the direction classification in optical flow. The image made by the new algorithm was defined as a \"kinetic map,\" and, by analysis using the kinetic map, a patient collation system and nodule detection system were constructed. By analysis that used an artificial neural network of certain feature vectors as kinetic map similarity, the collation system obtained good identification performance. Temporal subtraction processing between a current-status map with simulated nodule and previous-status map detected the region of abnormality as the simulated nodule. It is expected that our method of analysis will be useful as a screening examination for risk management and computer-aided diagnostic application in dynamic chest radiography.", "classifications": [ { "id": "Tsuchiya", "label": "Group Tsuchiya", "parent": "Tsuchiya", "type": "group" }, { "id": "Tsuchiya", "label": "Team Tsuchiya", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yuichiro", "last_name": "Tsuchiya", "name": null }, { "creator_type": "author", "first_name": "Yoshie", "last_name": "Kodera", "name": null } ], "identifiers": { "doi": { "normalized": "10.6009/jjrt.kj00004022979" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "16395243" } }, "mesh": [ { "descriptor": "Adult", "descriptor_ui": "D000328", "major_topic": false }, { "descriptor": "Algorithms", "descriptor_ui": "D000465", "major_topic": false }, { "descriptor": "Diagnosis, Computer-Assisted", "descriptor_ui": "D003936", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Kinetics", "descriptor_ui": "D007700", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Radiography, Thoracic", "descriptor_ui": "D013902", "major_topic": false }, { "descriptor": "Radiology Information Systems", "descriptor_ui": "D011873", "major_topic": false }, { "descriptor": "X-Ray Intensifying Screens", "descriptor_ui": "D014963", "major_topic": false } ], "publication": { "conference_name": null, "date": "2005 Dec 20", "date_precision": "day", "issue": "12", "normalized_date": "2005-12-20", "pages": "1666-1674", "proceedings_title": null, "publisher": "", "title": "Nihon Hoshasen Gijutsu Gakkai zasshi", "volume": "61", "year": 2005 }, "ssbd": { "database": [], "repository": [] }, "title": "Development of a kinetic analysis technique for PACS management and a screening examination in dynamic radiography.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "[chemical reaction: see text]. The stereocontrolled total synthesis of (-)-spirofungin A (1) and (+)-spirofungin B (2a), polyketide-type antibiotics having various antifungal activities, has been achieved employing the Weinreb amide 8, the alkyne 9, and the vinyl boronate 5 readily available from the common intermediate 10. The first synthesis proceeded with a longest linear sequence of 31 steps, affording (-)-1 and (+)-2a in 7.9% and 5.2% overall yields, respectively.", "classifications": [ { "id": "Sodeoka", "label": "Group Sodeoka", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Takeshi", "last_name": "Shimizu", "name": null }, { "creator_type": "author", "first_name": "Tomoharu", "last_name": "Satoh", "name": null }, { "creator_type": "author", "first_name": "Katsunori", "last_name": "Murakoshi", "name": null }, { "creator_type": "author", "first_name": "Mikiko", "last_name": "Sodeoka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/ol052039k" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "16320994" } }, "mesh": [ { "descriptor": "Antifungal Agents", "descriptor_ui": "D000935", "major_topic": false }, { "descriptor": "Catalysis", "descriptor_ui": "D002384", "major_topic": false }, { "descriptor": "Cyclization", "descriptor_ui": "D003500", "major_topic": false }, { "descriptor": "Molecular Structure", "descriptor_ui": "D015394", "major_topic": false }, { "descriptor": "Pyrans", "descriptor_ui": "D011714", "major_topic": false }, { "descriptor": "Spiro Compounds", "descriptor_ui": "D013141", "major_topic": false }, { "descriptor": "Stereoisomerism", "descriptor_ui": "D013237", "major_topic": false }, { "descriptor": "Streptomyces", "descriptor_ui": "D013302", "major_topic": false } ], "publication": { "conference_name": null, "date": "2005 Dec 8", "date_precision": "day", "issue": "25", "normalized_date": "2005-12-08", "pages": "5573-5576", "proceedings_title": null, "publisher": "", "title": "Organic letters", "volume": "7", "year": 2005 }, "ssbd": { "database": [], "repository": [] }, "title": "Asymmetric total synthesis of (-)-spirofungin A and (+)-spirofungin B.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Ion fluxes through membrane ion channels play crucial roles both in neuronal signaling and the homeostatic control of body electrolytes. Despite our knowledge about the respective ion channels, just how diversification of ion channel genes underlies adaptation of animals to the physical environment remains unknown. Here we systematically survey up to 160 putative ion channel genes in the genome of Ciona intestinalis and compare them with corresponding gene sets from the genomes of the nematode Chaenorhabditis elegans, the fruit fly Drosophila melanogaster, and the more closely related genomes of vertebrates. Ciona has a set of so-called \"prototype\" genes for ion channels regulating neuronal excitability, or for neurotransmitter receptors, suggesting that genes responsible for neuronal signaling in mammals appear to have diversified mainly via gene duplications of the more restricted members of ancestral genomes before the ascidian/vertebrate divergence. Most genes responsible for modulation of neuronal excitability and pain sensation are absent from the ascidian genome, suggesting that these genes arose after the divergence of urochordates. In contrast, the divergent genes encoding connexins, transient receptor potential-related channels and chloride channels, channels involved rather in homeostatic control, indicate gene duplication events unique to the ascidian lineage. Because several invertebrate-unique channel genes exist in Ciona genome, the crown group of extant vertebrates not only acquired novel channel genes via gene/genome duplications but also discarded some ancient genes that have persisted in invertebrates. Such genome-wide information of ion channel genes in basal chordates enables us to begin correlating the innovation and remodeling of genes with the adaptation of more recent chordates to their physical environment.", "classifications": [ { "id": "Nishida", "label": "Group Nishida", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yasushi", "last_name": "Okamura", "name": null }, { "creator_type": "author", "first_name": "Atsuo", "last_name": "Nishino", "name": null }, { "creator_type": "author", "first_name": "Yoshimichi", "last_name": "Murata", "name": null }, { "creator_type": "author", "first_name": "Koichi", "last_name": "Nakajo", "name": null }, { "creator_type": "author", "first_name": "Hirohide", "last_name": "Iwasaki", "name": null }, { "creator_type": "author", "first_name": "Yukio", "last_name": "Ohtsuka", "name": null }, { "creator_type": "author", "first_name": "Motoko", "last_name": "Tanaka-Kunishima", "name": null }, { "creator_type": "author", "first_name": "Nobuyuki", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Yuji", "last_name": "Hara", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Yoshida", "name": null }, { "creator_type": "author", "first_name": "Motohiro", "last_name": "Nishida", "name": null }, { "creator_type": "author", "first_name": "Haruo", "last_name": "Okado", "name": null }, { "creator_type": "author", "first_name": "Hirofumi", "last_name": "Watari", "name": null }, { "creator_type": "author", "first_name": "Ian A.", "last_name": "Meinertzhagen", "name": null }, { "creator_type": "author", "first_name": "Nori", "last_name": "Satoh", "name": null }, { "creator_type": "author", "first_name": "Kunitaro", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Yutaka", "last_name": "Satou", "name": null }, { "creator_type": "author", "first_name": "Yasunobu", "last_name": "Okada", "name": null }, { "creator_type": "author", "first_name": "Yasuo", "last_name": "Mori", "name": null } ], "identifiers": { "doi": { "normalized": "10.1152/physiolgenomics.00229.2004" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "15914577" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Caenorhabditis elegans", "descriptor_ui": "D017173", "major_topic": false }, { "descriptor": "Ciona intestinalis", "descriptor_ui": "D002938", "major_topic": false }, { "descriptor": "Databases, Genetic", "descriptor_ui": "D030541", "major_topic": false }, { "descriptor": "Drosophila melanogaster", "descriptor_ui": "D004331", "major_topic": false }, { "descriptor": "Electrolytes", "descriptor_ui": "D004573", "major_topic": false }, { "descriptor": "Evolution, Molecular", "descriptor_ui": "D019143", "major_topic": false }, { "descriptor": "Gap Junctions", "descriptor_ui": "D017629", "major_topic": false }, { "descriptor": "Gene Expression Regulation, Developmental", "descriptor_ui": "D018507", "major_topic": false }, { "descriptor": "Genome", "descriptor_ui": "D016678", "major_topic": false }, { "descriptor": "Genomics", "descriptor_ui": "D023281", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Ion Channels", "descriptor_ui": "D007473", "major_topic": false }, { "descriptor": "Ions", "descriptor_ui": "D007477", "major_topic": false }, { "descriptor": "Models, Biological", "descriptor_ui": "D008954", "major_topic": false }, { "descriptor": "Models, Genetic", "descriptor_ui": "D008957", "major_topic": false }, { "descriptor": "Phylogeny", "descriptor_ui": "D010802", "major_topic": false }, { "descriptor": "Potassium Channels", "descriptor_ui": "D015221", "major_topic": false }, { "descriptor": "Receptors, Glutamate", "descriptor_ui": "D017470", "major_topic": false }, { "descriptor": "Receptors, Nicotinic", "descriptor_ui": "D011978", "major_topic": false }, { "descriptor": "Ryanodine Receptor Calcium Release Channel", "descriptor_ui": "D019837", "major_topic": false }, { "descriptor": "Urochordata", "descriptor_ui": "D014561", "major_topic": false }, { "descriptor": "Water", "descriptor_ui": "D014867", "major_topic": false } ], "publication": { "conference_name": null, "date": "2005 Aug 11", "date_precision": "day", "issue": "3", "normalized_date": "2005-08-11", "pages": "269-282", "proceedings_title": null, "publisher": "", "title": "Physiological genomics", "volume": "22", "year": 2005 }, "ssbd": { "database": [], "repository": [] }, "title": "Comprehensive analysis of the ascidian genome reveals novel insights into the molecular evolution of ion channel genes.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Experiments of synthetic gene regulatory modules and theoretical studies have clarified the stochastic nature of gene expression. The establishment of methods to control the fluctuation in gene expression is an indispensable step to the synthesis of robust and reliable genetic modules. In this study, we evaluate the performances of several major mechanisms to attenuate the fluctuation in a single-gene expression; noise attenuation through the control of the ratio of the transcription rate to the translation one, the interaction between synthesized proteins and background molecules, and an autoregulatory negative feedback. We analytically derive the dependence of the noise intensity on the parameter values related to elementary reaction processes, optimal conditions to attenuate the noise, and the limitation of the attenuation for those mechanisms. Our results can be an important basis for selecting the most efficient combination of the components in the design and synthesis of robust and reliable genetic modules. Furthermore, the knowledge on the performances that we obtain can also play a role in understanding the design principle of the intracellular gene regulatory networks.", "classifications": [ { "id": "Kobayashi", "label": "Group Kobayashi", "parent": "Wakamoto", "type": "group" }, { "id": "Wakamoto", "label": "Team Wakamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yoshihiro", "last_name": "Morishita", "name": null }, { "creator_type": "author", "first_name": "Tetsuya J.", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Kazuyuki", "last_name": "Aihara", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.jtbi.2005.01.007" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "15862593" } }, "mesh": [ { "descriptor": "Computational Biology", "descriptor_ui": "D019295", "major_topic": false }, { "descriptor": "Feedback, Physiological", "descriptor_ui": "D025461", "major_topic": false }, { "descriptor": "Gene Expression Regulation", "descriptor_ui": "D005786", "major_topic": false }, { "descriptor": "Macromolecular Substances", "descriptor_ui": "D046911", "major_topic": false }, { "descriptor": "Models, Genetic", "descriptor_ui": "D008957", "major_topic": true }, { "descriptor": "Protein Biosynthesis", "descriptor_ui": "D014176", "major_topic": false }, { "descriptor": "Stochastic Processes", "descriptor_ui": "D013269", "major_topic": false }, { "descriptor": "Transcription, Genetic", "descriptor_ui": "D014158", "major_topic": false } ], "publication": { "conference_name": null, "date": "2005 Jul 21", "date_precision": "day", "issue": "2", "normalized_date": "2005-07-21", "pages": "241-264", "proceedings_title": null, "publisher": "", "title": "Journal of theoretical biology", "volume": "235", "year": 2005 }, "ssbd": { "database": [], "repository": [] }, "title": "Evaluation of the performance of mechanisms for noise attenuation in a single-gene expression.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Angiotensin II (Ang II) activates multiple signaling pathways leading to hyperplasia of cardiac fibroblasts. Reactive oxygen species (ROS) produced by Ang II stimulation are assumed to play pivotal roles in this process. Here, we show that ROS mediate Ang II-induced activation of nuclear factor of activated T cells (NFAT) in rat cardiac fibroblasts. Ang II-induced NFAT activation was suppressed by diphenyleneiodonium (an NADPH oxidase inhibitor), dominant negative (DN)-Rac, DN-p47(phox), and an inhibitor of Galpha(12/13) (Galpha(12/13)-specific regulator of G protein signaling domain of p115RhoGEF, p115-regulator of G protein signaling (RGS)). Stimulation of Ang II receptor increased the intracellular ROS level in a Rac- and p47(phox)-dependent manner. Because p115-RGS suppressed Ang II-induced Rac activation, Ang II receptor-coupled Galpha(12/13) mediated NFAT activation through ROS production by Rac activation. Ang II-induced nuclear translocation of the green fluorescent protein (GFP)-tagged amino-terminal region of NFAT4 (GFP-NFAT4) was suppressed by p115-RGS or BAPTA but not by diphenyleneiodonium. The expression of constitutively active (CA)-Galpha(12/13), CA-G translocation alpha(13), or CA-Rac increased the nuclear of GFP-NFAT4. These results suggest that NFAT activity is regulated by both Ca(2+)-dependent and ROS-dependent pathways. Furthermore, activation of c-Jun NH(2)-terminal kinase (JNK) induced by Ang II stimulation is required for NFAT activation because Ang II-induced NFAT activation was inhibited by SP600125, a selective JNK inhibitor. These results indicate that Ang II stimulates the nuclear translocation and activation of NFAT by integrated pathways including the activation of Galpha(12/13), Rac, NADPH oxidase, and JNK and that Galpha(12/13)-mediated ROS production is essential for NFAT transcriptional activation.", "classifications": [ { "id": "Nishida", "label": "Group Nishida", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Tomomi", "last_name": "Fujii", "name": null }, { "creator_type": "author", "first_name": "Naoya", "last_name": "Onohara", "name": null }, { "creator_type": "author", "first_name": "Yoshiko", "last_name": "Maruyama", "name": null }, { "creator_type": "author", "first_name": "Shihori", "last_name": "Tanabe", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Masashi", "last_name": "Fukutomi", "name": null }, { "creator_type": "author", "first_name": "Yuichi", "last_name": "Nagamatsu", "name": null }, { "creator_type": "author", "first_name": "Naoki", "last_name": "Nishihara", "name": null }, { "creator_type": "author", "first_name": "Ryuji", "last_name": "Inoue", "name": null }, { "creator_type": "author", "first_name": "Hideki", "last_name": "Sumimoto", "name": null }, { "creator_type": "author", "first_name": "Futoshi", "last_name": "Shibasaki", "name": null }, { "creator_type": "author", "first_name": "Taku", "last_name": "Nagao", "name": null }, { "creator_type": "author", "first_name": "Motohiro", "last_name": "Nishida", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Kurose", "name": null } ], "identifiers": { "doi": { "normalized": "10.1074/jbc.m409397200" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "15826947" } }, "mesh": [ { "descriptor": "Active Transport, Cell Nucleus", "descriptor_ui": "D021581", "major_topic": false }, { "descriptor": "Adenoviridae", "descriptor_ui": "D000256", "major_topic": false }, { "descriptor": "Angiotensin II", "descriptor_ui": "D000804", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Anthracenes", "descriptor_ui": "D000873", "major_topic": false }, { "descriptor": "Blotting, Western", "descriptor_ui": "D015153", "major_topic": false }, { "descriptor": "Calcium", "descriptor_ui": "D002118", "major_topic": false }, { "descriptor": "Cell Nucleus", "descriptor_ui": "D002467", "major_topic": false }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "DNA-Binding Proteins", "descriptor_ui": "D004268", "major_topic": false }, { "descriptor": "Enzyme Inhibitors", "descriptor_ui": "D004791", "major_topic": false }, { "descriptor": "Fibroblasts", "descriptor_ui": "D005347", "major_topic": false }, { "descriptor": "Genes, Dominant", "descriptor_ui": "D005799", "major_topic": false }, { "descriptor": "Green Fluorescent Proteins", "descriptor_ui": "D049452", "major_topic": false }, { "descriptor": "GTP-Binding Protein alpha Subunits, G12-G13", "descriptor_ui": "D044365", "major_topic": false }, { "descriptor": "Heart Ventricles", "descriptor_ui": "D006352", "major_topic": false }, { "descriptor": "JNK Mitogen-Activated Protein Kinases", "descriptor_ui": "D048031", "major_topic": false }, { "descriptor": "MAP Kinase Kinase 4", "descriptor_ui": "D048670", "major_topic": false }, { "descriptor": "Mitogen-Activated Protein Kinase Kinases", "descriptor_ui": "D020929", "major_topic": false }, { "descriptor": "Models, Biological", "descriptor_ui": "D008954", "major_topic": false }, { "descriptor": "Models, Chemical", "descriptor_ui": "D008956", "major_topic": false }, { "descriptor": "Myocardium", "descriptor_ui": "D009206", "major_topic": false }, { "descriptor": "NADPH Oxidases", "descriptor_ui": "D019255", "major_topic": false }, { "descriptor": "NFATC Transcription Factors", "descriptor_ui": "D050778", "major_topic": false }, { "descriptor": "Nuclear Proteins", "descriptor_ui": "D009687", "major_topic": false }, { "descriptor": "Onium Compounds", "descriptor_ui": "D009861", "major_topic": false }, { "descriptor": "Phosphoproteins", "descriptor_ui": "D010750", "major_topic": false }, { "descriptor": "Phosphorylation", "descriptor_ui": "D010766", "major_topic": false }, { "descriptor": "Plasmids", "descriptor_ui": "D010957", "major_topic": false }, { "descriptor": "Protein Binding", "descriptor_ui": "D011485", "major_topic": false }, { "descriptor": "Protein Structure, Tertiary", "descriptor_ui": "D017434", "major_topic": false }, { "descriptor": "Protein Transport", "descriptor_ui": "D021381", "major_topic": false }, { "descriptor": "rac GTP-Binding Proteins", "descriptor_ui": "D020744", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Rats, Sprague-Dawley", "descriptor_ui": "D017207", "major_topic": false }, { "descriptor": "Reactive Oxygen Species", "descriptor_ui": "D017382", "major_topic": true }, { "descriptor": "Receptors, Angiotensin", "descriptor_ui": "D011945", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Time Factors", "descriptor_ui": "D013997", "major_topic": false }, { "descriptor": "Transcription Factors", "descriptor_ui": "D014157", "major_topic": false }, { "descriptor": "Transcriptional Activation", "descriptor_ui": "D015533", "major_topic": false } ], "publication": { "conference_name": null, "date": "2005 Jun 17", "date_precision": "day", "issue": "24", "normalized_date": "2005-06-17", "pages": "23041-23047", "proceedings_title": null, "publisher": "", "title": "The Journal of biological chemistry", "volume": "280", "year": 2005 }, "ssbd": { "database": [], "repository": [] }, "title": "Galpha12/13-mediated production of reactive oxygen species is critical for angiotensin receptor-induced NFAT activation in cardiac fibroblasts.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "In the present study, we examined signal transduction mechanism of reactive oxygen species (ROS) production and the role of ROS in angiotensin II-induced activation of mitogen-activated protein kinases (MAPKs) in rat neonatal cardiomyocytes. Among three MAPKs, c-Jun NH(2)-terminal kinase (JNK) and p38 MAPK required ROS production for activation, as an NADPH oxidase inhibitor, diphenyleneiodonium, inhibited the activation. The angiotensin II-induced activation of JNK and p38 MAPK was also inhibited by the expression of the Galpha(12/13)-specific regulator of G protein signaling (RGS) domain, a specific inhibitor of Galpha(12/13), but not by an RGS domain specific for Galpha(q). Constitutively active Galpha(12)- or Galpha(13)-induced activation of JNK and p38 MAPK, but not extracellular signal-regulated kinase (ERK), was inhibited by diphenyleneiodonium. Angiotensin II receptor stimulation rapidly activated Galpha(13), which was completely inhibited by the Galpha(12/13)-specific RGS domain. Furthermore, the Galpha(12/13)-specific but not the Galpha(q)-specific RGS domain inhibited angiotensin II-induced ROS production. Dominant negative Rac inhibited angiotensin II-stimulated ROS production, JNK activation, and p38 MAPK activation but did not affect ERK activation. Rac activation was mediated by Rho and Rho kinase, because Rac activation was inhibited by C3 toxin and a Rho kinase inhibitor, Y27632. Furthermore, angiotensin II-induced Rho activation was inhibited by Galpha(12/13)-specific RGS domain but not dominant negative Rac. An inhibitor of epidermal growth factor receptor kinase AG1478 did not affect angiotensin II-induced JNK activation cascade. These results suggest that Galpha(12/13)-mediated ROS production through Rho and Rac is essential for JNK and p38 MAPK activation.", "classifications": [ { "id": "Nishida", "label": "Group Nishida", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Motohiro", "last_name": "Nishida", "name": null }, { "creator_type": "author", "first_name": "Shihori", "last_name": "Tanabe", "name": null }, { "creator_type": "author", "first_name": "Yoshiko", "last_name": "Maruyama", "name": null }, { "creator_type": "author", "first_name": "Supachoke", "last_name": "Mangmool", "name": null }, { "creator_type": "author", "first_name": "Kyoji", "last_name": "Urayama", "name": null }, { "creator_type": "author", "first_name": "Yuichi", "last_name": "Nagamatsu", "name": null }, { "creator_type": "author", "first_name": "Shuichi", "last_name": "Takagahara", "name": null }, { "creator_type": "author", "first_name": "Justin H.", "last_name": "Turner", "name": null }, { "creator_type": "author", "first_name": "Tohru", "last_name": "Kozasa", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Yoji", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Toru", "last_name": "Kawanishi", "name": null }, { "creator_type": "author", "first_name": "Ryuji", "last_name": "Inoue", "name": null }, { "creator_type": "author", "first_name": "Taku", "last_name": "Nagao", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Kurose", "name": null } ], "identifiers": { "doi": { "normalized": "10.1074/jbc.m409710200" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "15743761" } }, "mesh": [ { "descriptor": "Angiotensin Receptor Antagonists", "descriptor_ui": "D057911", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Animals, Newborn", "descriptor_ui": "D000831", "major_topic": false }, { "descriptor": "Benzimidazoles", "descriptor_ui": "D001562", "major_topic": false }, { "descriptor": "Biphenyl Compounds", "descriptor_ui": "D001713", "major_topic": false }, { "descriptor": "Enzyme Activation", "descriptor_ui": "D004789", "major_topic": false }, { "descriptor": "GTP-Binding Protein alpha Subunits, G12-G13", "descriptor_ui": "D044365", "major_topic": false }, { "descriptor": "JNK Mitogen-Activated Protein Kinases", "descriptor_ui": "D048031", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Myocytes, Cardiac", "descriptor_ui": "D032383", "major_topic": false }, { "descriptor": "p38 Mitogen-Activated Protein Kinases", "descriptor_ui": "D048051", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Rats, Sprague-Dawley", "descriptor_ui": "D017207", "major_topic": false }, { "descriptor": "Reactive Oxygen Species", "descriptor_ui": "D017382", "major_topic": false }, { "descriptor": "Receptors, Angiotensin", "descriptor_ui": "D011945", "major_topic": false }, { "descriptor": "Tetrazoles", "descriptor_ui": "D013777", "major_topic": false } ], "publication": { "conference_name": null, "date": "2005 May 6", "date_precision": "day", "issue": "18", "normalized_date": "2005-05-06", "pages": "18434-18441", "proceedings_title": null, "publisher": "", "title": "The Journal of biological chemistry", "volume": "280", "year": 2005 }, "ssbd": { "database": [], "repository": [] }, "title": "G alpha 12/13- and reactive oxygen species-dependent activation of c-Jun NH2-terminal kinase and p38 mitogen-activated protein kinase by angiotensin receptor stimulation in rat neonatal cardiomyocytes.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Mammalian mitogen-activated protein kinase (MAPK) cascades control various cellular events, ranging from cell growth to apoptosis, in response to external stimuli. A conserved docking site, termed DVD, is found in the mammalian MAP kinase kinases (MAPKKs) belonging to the three major subfamilies, namely MEK1, MKK4/7, and MKK3/6. The DVD sites bind to their specific upstream MAP kinase kinase kinases (MAPKKKs), including MTK1 (MEKK4), ASK1, TAK1, TAO2, MEKK1, and Raf-1. DVD site is a stretch of about 20 amino acids immediately on the C-terminal side of the MAPKK catalytic domain. Mutations in the DVD site strongly inhibited MAPKKs from binding to, and being activated by, their specific MAPKKKs, both in vitro and in vivo. DVD site mutants could not be activated by various external stimuli in vivo. Synthetic DVD oligopeptides inhibited specific MAPKK activation, both in vitro and in vivo, demonstrating the critical importance of the DVD docking in MAPK signaling.", "classifications": [ { "id": "Takekawa", "label": "Group Takekawa", "parent": "Takekawa", "type": "group" }, { "id": "Takekawa", "label": "Team Takekawa", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Mutsuhiro", "last_name": "Takekawa", "name": null }, { "creator_type": "author", "first_name": "Kazuo", "last_name": "Tatebayashi", "name": null }, { "creator_type": "author", "first_name": "Haruo", "last_name": "Saito", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.molcel.2005.04.001" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "15866172" } }, "mesh": [ { "descriptor": "Amino Acid Sequence", "descriptor_ui": "D000595", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Binding Sites", "descriptor_ui": "D001665", "major_topic": false }, { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "Enzyme Activation", "descriptor_ui": "D004789", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "MAP Kinase Kinase Kinases", "descriptor_ui": "D020930", "major_topic": false }, { "descriptor": "MAP Kinase Signaling System", "descriptor_ui": "D020935", "major_topic": false }, { "descriptor": "Mitogen-Activated Protein Kinase Kinases", "descriptor_ui": "D020929", "major_topic": false }, { "descriptor": "Molecular Sequence Data", "descriptor_ui": "D008969", "major_topic": false }, { "descriptor": "Peptides", "descriptor_ui": "D010455", "major_topic": false }, { "descriptor": "Protein Binding", "descriptor_ui": "D011485", "major_topic": false }, { "descriptor": "Protein Folding", "descriptor_ui": "D017510", "major_topic": false }, { "descriptor": "Sequence Alignment", "descriptor_ui": "D016415", "major_topic": false }, { "descriptor": "Two-Hybrid System Techniques", "descriptor_ui": "D020798", "major_topic": false } ], "publication": { "conference_name": null, "date": "2005 Apr 29", "date_precision": "day", "issue": "3", "normalized_date": "2005-04-29", "pages": "295-306", "proceedings_title": null, "publisher": "", "title": "Molecular cell", "volume": "18", "year": 2005 }, "ssbd": { "database": [], "repository": [] }, "title": "Conserved docking site is essential for activation of mammalian MAP kinase kinases by specific MAP kinase kinase kinases.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Information processing by random feed-forward networks consisting of units with a sigmoidal input-output response is studied by focusing on the dependence of its outputs on the number of parallel paths M. It is found that the system leads to a combination of on-off outputs when M less or similar to 7, while for M greater or similar to 7, chaotic dynamics arises, resulting in a continuous distribution of outputs. This universality of the critical number M approximately 7 is explained by a combinatorial explosion, i.e., the dominance of factorial over exponential increase. The relevance of the result to biological problems is briefly discussed.", "classifications": [ { "id": "Ishihara", "label": "Group Ishihara", "parent": "Sawai", "type": "group" }, { "id": "Sawai", "label": "Team Sawai", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Shuji", "last_name": "Ishihara", "name": null }, { "creator_type": "author", "first_name": "Kunihiko", "last_name": "Kaneko", "name": null } ], "identifiers": { "doi": { "normalized": "10.1103/physrevlett.94.058102" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "15783703" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Computer Simulation", "descriptor_ui": "D003198", "major_topic": false }, { "descriptor": "Differential Threshold", "descriptor_ui": "D004056", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Models, Neurological", "descriptor_ui": "D008959", "major_topic": true }, { "descriptor": "Models, Statistical", "descriptor_ui": "D015233", "major_topic": true }, { "descriptor": "Nerve Net", "descriptor_ui": "D009415", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Nonlinear Dynamics", "descriptor_ui": "D017711", "major_topic": true }, { "descriptor": "Synaptic Transmission", "descriptor_ui": "D009435", "major_topic": false } ], "publication": { "conference_name": null, "date": "2005 Feb 11", "date_precision": "day", "issue": "5", "normalized_date": "2005-02-11", "pages": "058102", "proceedings_title": null, "publisher": "", "title": "Physical review letters", "volume": "94", "year": 2005 }, "ssbd": { "database": [], "repository": [] }, "title": "Magic number 7+/-2 in networks of threshold dynamics.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Because intracellular processes are inherently noisy, stochastic reactions process noisy signals in cellular signal transduction. One essential feature of biological signal transduction systems is the amplification of small changes in input signals. However, small random changes in the input signals could also be amplified, and the transduction reaction can also generate noise. Here, we show theoretically how the abrupt response of ultrasensitive signal-transduction reactions results in the generation of large inherent noise and the high amplification of input noise. The inherently generated noise propagates with amplification through intracellular molecular network. We discuss how the contribution of such transmitted noise can be shown experimentally. Our results imply that the switch-like behavior of signal transduction could be limited by noise; however, high amplification reaction could be advantageous to generate large noise, which would be essential to maintain behavioral variability.", "classifications": [ { "id": "Fujimoto", "label": "Group Fujimoto", "parent": "Ueda", "type": "group" }, { "id": "Ueda", "label": "Team Ueda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Tatsuo", "last_name": "Shibata", "name": null }, { "creator_type": "author", "first_name": "Koichi", "last_name": "Fujimoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1073/pnas.0403350102" }, "pmcid": { "normalized": "PMC544281" }, "pmid": { "normalized": "15625116" } }, "mesh": [ { "descriptor": "Gene Expression", "descriptor_ui": "D015870", "major_topic": false }, { "descriptor": "Models, Biological", "descriptor_ui": "D008954", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": true } ], "publication": { "conference_name": null, "date": "2005 Jan 11", "date_precision": "day", "issue": "2", "normalized_date": "2005-01-11", "pages": "331-336", "proceedings_title": null, "publisher": "", "title": "Proceedings of the National Academy of Sciences of the United States of America", "volume": "102", "year": 2005 }, "ssbd": { "database": [], "repository": [] }, "title": "Noisy signal amplification in ultrasensitive signal transduction.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "We developed a computational technique to assist in the large-scale identification of charged metabolites. The electrophoretic mobility of metabolites in capillary electrophoresis-mass spectrometry (CE-MS) was predicted from their structure, using an ensemble of artificial neural networks (ANNs). Comparison between relative migration times of 241 various cations measured by CE-MS and predicted by a trained ANN ensemble produced a correlation coefficient of 0.931. When we used our technique to characterize all metabolites listed in the KEGG ligand database, the correct compounds among the top three candidates were predicted in 78.0% of cases. We suggest that this approach can be used for the prediction of the migration time of any cation and that it represents a powerful method for the identification of uncharacterized CE-MS peaks in metabolome analysis.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Masahiro", "last_name": "Sugimoto", "name": null }, { "creator_type": "author", "first_name": "Shinichi", "last_name": "Kikuchi", "name": null }, { "creator_type": "author", "first_name": "Masanori", "last_name": "Arita", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Takaaki", "last_name": "Nishioka", "name": null }, { "creator_type": "author", "first_name": "Masaru", "last_name": "Tomita", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/ac048950g" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "15623281" } }, "mesh": [ { "descriptor": "Cations", "descriptor_ui": "D002412", "major_topic": false }, { "descriptor": "Electrophoresis, Capillary", "descriptor_ui": "D019075", "major_topic": false }, { "descriptor": "Mass Spectrometry", "descriptor_ui": "D013058", "major_topic": false }, { "descriptor": "Neural Networks, Computer", "descriptor_ui": "D016571", "major_topic": true } ], "publication": { "conference_name": null, "date": "2005 Jan 1", "date_precision": "day", "issue": "1", "normalized_date": "2005-01-01", "pages": "78-84", "proceedings_title": null, "publisher": "", "title": "Analytical chemistry", "volume": "77", "year": 2005 }, "ssbd": { "database": [], "repository": [] }, "title": "Large-scale prediction of cationic metabolite identity and migration time in capillary electrophoresis mass spectrometry using artificial neural networks.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Understanding how p53 activity is regulated is crucial in elucidating mechanisms of cellular defense against cancer. Genetic data indicate that Mdmx as well as Mdm2 plays a major role in maintaining p53 activity at low levels in nonstressed cells. However, biochemical mechanisms of how Mdmx regulates p53 activity are not well understood. Through identification of Mdmx-binding proteins, we found that 14-3-3 proteins are associated with Mdmx. Mdmx harbors a consensus sequence for binding of 14-3-3. Serine 367 (S367) is located within the putative binding sequence for 14-3-3, and its substitution with alanine (S367A) abolishes binding of Mdmx to 14-3-3. Transfection assays indicated that the S367A mutation, in cooperation with Mdm2, enhances the ability of Mdmx to repress the transcriptional activity of p53. The S367A mutant is more resistant to Mdm2-dependent ubiquitination and degradation than wild-type Mdmx, and Mdmx phosphorylated at S367 is preferentially degraded by Mdm2. Several types of DNA damage markedly enhance S367 phosphorylation, coinciding with increased binding of Mdmx to 14-3-3 and accelerated Mdmx degradation. Furthermore, promotion of growth of normal human fibroblasts after introduction of Mdmx is enhanced by the S367 mutation. We propose that Mdmx phosphorylation at S367 plays an important role in p53 activation after DNA damage by triggering Mdm2-dependent degradation of Mdmx.", "classifications": [ { "id": "Okamoto", "label": "Group Okamoto", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Koji", "last_name": "Okamoto", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Kashima", "name": null }, { "creator_type": "author", "first_name": "Yaron", "last_name": "Pereg", "name": null }, { "creator_type": "author", "first_name": "Michiko", "last_name": "Ishida", "name": null }, { "creator_type": "author", "first_name": "Satomi", "last_name": "Yamazaki", "name": null }, { "creator_type": "author", "first_name": "Ayumi", "last_name": "Nota", "name": null }, { "creator_type": "author", "first_name": "Amina", "last_name": "Teunisse", "name": null }, { "creator_type": "author", "first_name": "Domenico", "last_name": "Migliorini", "name": null }, { "creator_type": "author", "first_name": "Issay", "last_name": "Kitabayashi", "name": null }, { "creator_type": "author", "first_name": "Jean-Christophe", "last_name": "Marine", "name": null }, { "creator_type": "author", "first_name": "Carol", "last_name": "Prives", "name": null }, { "creator_type": "author", "first_name": "Yosef", "last_name": "Shiloh", "name": null }, { "creator_type": "author", "first_name": "Aart G.", "last_name": "Jochemsen", "name": null }, { "creator_type": "author", "first_name": "Yoichi", "last_name": "Taya", "name": null } ], "identifiers": { "doi": { "normalized": "10.1128/mcb.25.21.9608-9620.2005" }, "pmcid": { "normalized": "PMC1265801" }, "pmid": { "normalized": "16227609" } }, "mesh": [ { "descriptor": "14-3-3 Proteins", "descriptor_ui": "D048948", "major_topic": false }, { "descriptor": "Amino Acid Sequence", "descriptor_ui": "D000595", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Cycle Proteins", "descriptor_ui": "D018797", "major_topic": false }, { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "Chlorocebus aethiops", "descriptor_ui": "D002522", "major_topic": false }, { "descriptor": "DNA Damage", "descriptor_ui": "D004249", "major_topic": true }, { "descriptor": "Fibroblasts", "descriptor_ui": "D005347", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Molecular Sequence Data", "descriptor_ui": "D008969", "major_topic": false }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": false }, { "descriptor": "Nuclear Proteins", "descriptor_ui": "D009687", "major_topic": false }, { "descriptor": "Phosphorylation", "descriptor_ui": "D010766", "major_topic": false }, { "descriptor": "Proteasome Endopeptidase Complex", "descriptor_ui": "D046988", "major_topic": false }, { "descriptor": "Protein Binding", "descriptor_ui": "D011485", "major_topic": false }, { "descriptor": "Proto-Oncogene Proteins", "descriptor_ui": "D011518", "major_topic": false }, { "descriptor": "Proto-Oncogene Proteins c-mdm2", "descriptor_ui": "D051736", "major_topic": false }, { "descriptor": "Serine", "descriptor_ui": "D012694", "major_topic": false }, { "descriptor": "Tumor Suppressor Protein p53", "descriptor_ui": "D016159", "major_topic": false } ], "publication": { "conference_name": null, "date": "2005 Nov", "date_precision": "unknown", "issue": "21", "normalized_date": null, "pages": "9608-9620", "proceedings_title": null, "publisher": "", "title": "Molecular and cellular biology", "volume": "25", "year": 2005 }, "ssbd": { "database": [], "repository": [] }, "title": "DNA damage-induced phosphorylation of MdmX at serine 367 activates p53 by targeting MdmX for Mdm2-dependent degradation.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Transient responses of signaling molecules are seen in a wide variety of cellular processes that are mediated by distinct molecular mechanisms. Although transient responses might intuitively be thought to depend on the absolute concentration of growth factors or the intensity of stimulation, we here introduce that some transient responses are prompted by temporal rate of increase of stimulation, rather than intensity of stimulation, by three independent mechanisms. These include the Ras system with fast activation and slow inactivation, the ERK-dependent negative feedback loop system, and the receptor degradation system, all of which can be commonly seen in various signaling networks. In addition, we show the distinct transient and steady state characteristics of these systems.", "classifications": [ { "id": "Kuroda", "label": "Group Kuroda", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yu-ichi", "last_name": "Ozaki", "name": null }, { "creator_type": "author", "first_name": "Satoru", "last_name": "Sasagawa", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Kuroda", "name": null } ], "identifiers": { "doi": { "normalized": "10.1093/jb/mvi084" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "16002986" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Computer Simulation", "descriptor_ui": "D003198", "major_topic": true }, { "descriptor": "Enzyme Activation", "descriptor_ui": "D004789", "major_topic": false }, { "descriptor": "Extracellular Signal-Regulated MAP Kinases", "descriptor_ui": "D048049", "major_topic": false }, { "descriptor": "Kinetics", "descriptor_ui": "D007700", "major_topic": false }, { "descriptor": "Models, Biological", "descriptor_ui": "D008954", "major_topic": true }, { "descriptor": "PC12 Cells", "descriptor_ui": "D016716", "major_topic": false }, { "descriptor": "ras Proteins", "descriptor_ui": "D018631", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": true } ], "publication": { "conference_name": null, "date": "2005 Jun", "date_precision": "unknown", "issue": "6", "normalized_date": null, "pages": "659-663", "proceedings_title": null, "publisher": "", "title": "Journal of biochemistry", "volume": "137", "year": 2005 }, "ssbd": { "database": [], "repository": [] }, "title": "Dynamic characteristics of transient responses.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Gene regulatory networks contain several substructures called network motifs, which frequently exist throughout the networks. One of such motifs found in Escherichia coli, Saccharomyces cerevisiae, and Drosophila melanogaster is the feed-forward loop, in which an effector regulates its target by a direct regulatory interaction and an indirect interaction mediated by another gene product. Here, we theoretically analyze the behavior of networks that contain feed-forward loops cross talking to each other. In response to levels of the effecter, such networks can generate multiple rise-and-fall temporal expression profiles and spatial stripes, which are typically observed in developmental processes. The mechanism to generate these responses reveals the way of inferring the regulatory pathways from experimental results. Our database study of gene regulatory networks indicates that most feed-forward loops actually cross talk. We discuss how the feed-forward loops and their cross talks can play important roles in morphogenesis.", "classifications": [ { "id": "Ishihara", "label": "Group Ishihara", "parent": "Sawai", "type": "group" }, { "id": "Sawai", "label": "Team Sawai", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Shuji", "last_name": "Ishihara", "name": null }, { "creator_type": "author", "first_name": "Koichi", "last_name": "Fujimoto", "name": null }, { "creator_type": "author", "first_name": "Tatsuo", "last_name": "Shibata", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/j.1365-2443.2005.00897.x" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "16236132" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Drosophila melanogaster", "descriptor_ui": "D004331", "major_topic": false }, { "descriptor": "Escherichia coli", "descriptor_ui": "D004926", "major_topic": false }, { "descriptor": "Feedback, Physiological", "descriptor_ui": "D025461", "major_topic": false }, { "descriptor": "Gene Expression Regulation", "descriptor_ui": "D005786", "major_topic": true }, { "descriptor": "Models, Genetic", "descriptor_ui": "D008957", "major_topic": false }, { "descriptor": "Saccharomyces cerevisiae", "descriptor_ui": "D012441", "major_topic": false }, { "descriptor": "Transcription Factors", "descriptor_ui": "D014157", "major_topic": false }, { "descriptor": "Transcription, Genetic", "descriptor_ui": "D014158", "major_topic": false } ], "publication": { "conference_name": null, "date": "2005 Nov", "date_precision": "unknown", "issue": "11", "normalized_date": null, "pages": "1025-1038", "proceedings_title": null, "publisher": "", "title": "Genes to cells : devoted to molecular & cellular mechanisms", "volume": "10", "year": 2005 }, "ssbd": { "database": [], "repository": [] }, "title": "Cross talking of network motifs in gene regulation that generates temporal pulses and spatial stripes.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Lung cancers have become the leading cause of cancer deaths in Japan, claiming more than 55 000 lives annually. Unfortunately, substantial improvement in terms of cure rates has not been achieved over the last two decades, although during the same period of time in-depth basic knowledge of the molecular mechanisms, which underlies carcinogenesis and progression of this deadly group of neoplasms, has accumulated at an amazing pace. It has consequently become evident that they have many shared but also distinct features, when comparisons are made not only with other common epithelial cancers of adults, such as colon cancer, but also within the various histologic types of lung cancers themselves. This review article provides an up-date on cutting-edge research into the following three different topics, from which important new insights have been obtained. The first concerns genetic instability, especially chromosome instability, and checkpoint failure in lung cancers. Second, we deal with EGFR mutations, which shows revealing specificities in various aspects. Finally, advances in the expression profiling analysis of both transcriptomes and proteomes of lung cancers are summarized.", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Shuta", "last_name": "Tomida", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null }, { "creator_type": "author", "first_name": "Kiyoshi", "last_name": "Yanagisawa", "name": null }, { "creator_type": "author", "first_name": "Tetsuya", "last_name": "Mitsudomi", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Takahashi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/j.1349-7006.2005.00021.x" }, "pmcid": { "normalized": "PMC11158112" }, "pmid": { "normalized": "15723649" } }, "mesh": [ { "descriptor": "Adenocarcinoma", "descriptor_ui": "D000230", "major_topic": false }, { "descriptor": "Chromosomal Instability", "descriptor_ui": "D043171", "major_topic": true }, { "descriptor": "Gene Expression Profiling", "descriptor_ui": "D020869", "major_topic": false }, { "descriptor": "Genes, cdc", "descriptor_ui": "D018816", "major_topic": false }, { "descriptor": "Genes, erbB-1", "descriptor_ui": "D018773", "major_topic": false }, { "descriptor": "Genes, ras", "descriptor_ui": "D011905", "major_topic": false }, { "descriptor": "Genes, Tumor Suppressor", "descriptor_ui": "D016147", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Lung Neoplasms", "descriptor_ui": "D008175", "major_topic": false }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": true }, { "descriptor": "Proteome", "descriptor_ui": "D020543", "major_topic": true } ], "publication": { "conference_name": null, "date": "2005 Feb", "date_precision": "unknown", "issue": "2", "normalized_date": null, "pages": "63-68", "proceedings_title": null, "publisher": "", "title": "Cancer science", "volume": "96", "year": 2005 }, "ssbd": { "database": [], "repository": [] }, "title": "Throwing new light on lung cancer pathogenesis: updates on three recent topics.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The emergence of variation and subsequent inheritance of the emergent characteristics in a clonal population of bacteria is considered as evidence for epigenetic processes in the cell. We report here the results of experiments in which we quantitatively examined variations in single Escherichia coli cells with an identical genetic endowment in order to establish whether certain characteristics of single cells were inherited by their descendants maintained in a uniform environment. Significantly large variations of interdivision time, initial length, and final length were observed from generation to generation. Comparing the generations shows that interdivision time had no correlation with that of the consecutive generations, whereas those of initial length and final length were positively correlated with those of neighbouring generations.", "classifications": [ { "id": "Wakamoto", "label": "Group Wakamoto", "parent": "Wakamoto", "type": "group" }, { "id": "Wakamoto", "label": "Team Wakamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yuichi", "last_name": "Wakamoto", "name": null }, { "creator_type": "author", "first_name": "Jeremy", "last_name": "Ramsden", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Yasuda", "name": null } ], "identifiers": { "doi": { "normalized": "10.1039/b409860a" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "15724159" } }, "mesh": [ { "descriptor": "Bacteriological Techniques", "descriptor_ui": "D001431", "major_topic": false }, { "descriptor": "Cell Cycle", "descriptor_ui": "D002453", "major_topic": false }, { "descriptor": "Cell Division", "descriptor_ui": "D002455", "major_topic": false }, { "descriptor": "Epigenesis, Genetic", "descriptor_ui": "D044127", "major_topic": true }, { "descriptor": "Escherichia coli", "descriptor_ui": "D004926", "major_topic": false }, { "descriptor": "Microchip Analytical Procedures", "descriptor_ui": "D046208", "major_topic": false } ], "publication": { "conference_name": null, "date": "2005 Mar", "date_precision": "unknown", "issue": "3", "normalized_date": null, "pages": "311-317", "proceedings_title": null, "publisher": "", "title": "The Analyst", "volume": "130", "year": 2005 }, "ssbd": { "database": [], "repository": [] }, "title": "Single-cell growth and division dynamics showing epigenetic correlations.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Purkinje fibers play essential roles in impulse propagation to the ventricles, and their functional impairment can become arrhythmogenic. However, little is known about precise spatiotemporal pattern(s) of interconnection between Purkinje-fiber network and the underlying ventricular myocardium within the heart. To address this issue, we simultaneously visualized intracellular Ca(2+) dynamics at Purkinje fibers and subjacent ventricular myocytes in Langendorff-perfused rat hearts using multi-pinhole type, rapid-scanning confocal microscopy. Under recording of electrocardiogram at room temperature spatiotemporal changes in fluo3-fluorescence intensity were visualized on the subendocardial region of the right-ventricular septum. Staining of the heart with either fluo3, acetylthiocholine iodide (ATCHI), or di-4-ANEPPS revealed characteristic structures of Purkinje fibers. During sinus rhythm (about 60 bpm) or atrial pacing (up to 3 Hz) each Purkinje-fiber exhibited spatiotemporally synchronous Ca(2+) transients nearly simultaneously to ventricular excitation. Ca(2+) transients in individual fibers were still synchronized within the Purkinje-fiber network not only under high-K(+) (8 mM) perfusion-induced Purkinje-to-ventricular (P-V) conduction delay, but also under unidirectional, orthodromic P-V block produced by 10-mM K(+) perfusion. While spontaneous, asynchronous intracellular Ca(2+) waves were identified in injured fibers of Purkinje network locally, surrounding fibers still exhibited Ca(2+) transients synchronously to ventricular excitation. In summary, these results are the first demonstration of intracellular Ca(2+) dynamics in the Purkinje-fiber network in situ. The synchronous Ca(2+) transients, preserved even under P-V conduction disturbances or under emergence of Ca(2+) waves, imply a syncytial role of Purkinje fibers as a specialized conduction system, whereas unidirectional block at P-V junctions indicates a substrate for reentrant arrhythmias.", "classifications": [ { "id": "Tanaka", "label": "Group Tanaka", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Tetsu", "last_name": "Hamamoto", "name": null }, { "creator_type": "author", "first_name": "Hideo", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Hiroki", "last_name": "Mani", "name": null }, { "creator_type": "author", "first_name": "Takuji", "last_name": "Tanabe", "name": null }, { "creator_type": "author", "first_name": "Katsuji", "last_name": "Fujiwara", "name": null }, { "creator_type": "author", "first_name": "Takuo", "last_name": "Nakagami", "name": null }, { "creator_type": "author", "first_name": "Minoru", "last_name": "Horie", "name": null }, { "creator_type": "author", "first_name": "Masahito", "last_name": "Oyamada", "name": null }, { "creator_type": "author", "first_name": "Tetsuro", "last_name": "Takamatsu", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.yjmcc.2005.01.004" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "15808833" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Calcium", "descriptor_ui": "D002118", "major_topic": false }, { "descriptor": "Cations, Divalent", "descriptor_ui": "D002413", "major_topic": false }, { "descriptor": "Electrocardiography", "descriptor_ui": "D004562", "major_topic": false }, { "descriptor": "Endocardium", "descriptor_ui": "D004699", "major_topic": false }, { "descriptor": "Heart Ventricles", "descriptor_ui": "D006352", "major_topic": false }, { "descriptor": "In Vitro Techniques", "descriptor_ui": "D066298", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Microscopy, Confocal", "descriptor_ui": "D018613", "major_topic": false }, { "descriptor": "Myocardial Contraction", "descriptor_ui": "D009200", "major_topic": true }, { "descriptor": "Myocytes, Cardiac", "descriptor_ui": "D032383", "major_topic": false }, { "descriptor": "Purkinje Fibers", "descriptor_ui": "D011690", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Rats, Wistar", "descriptor_ui": "D017208", "major_topic": false } ], "publication": { "conference_name": null, "date": "2005 Apr", "date_precision": "unknown", "issue": "4", "normalized_date": null, "pages": "561-569", "proceedings_title": null, "publisher": "", "title": "Journal of molecular and cellular cardiology", "volume": "38", "year": 2005 }, "ssbd": { "database": [], "repository": [] }, "title": "In situ Ca2+ dynamics of Purkinje fibers and its interconnection with subjacent ventricular myocytes.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Noninvasive, straightforward methods to inactivate selected proteins in living cells with high spatiotemporal resolution are needed. Chromophore-assisted laser inactivation (CALI) can be used to photochemically inactivate proteins, but it has several drawbacks, such as procedural complexity and nonspecific photodamage. Here we show that by application of multiphoton excitation to CALI, enhanced green fluorescent protein (EGFP) is an effective chromophore for inactivation of a protein's function without nonspecific photodamage in living mammalian cells.", "classifications": [ { "id": "Tanaka", "label": "Group Tanaka", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Takuji", "last_name": "Tanabe", "name": null }, { "creator_type": "author", "first_name": "Masahito", "last_name": "Oyamada", "name": null }, { "creator_type": "author", "first_name": "Katsumasa", "last_name": "Fujita", "name": null }, { "creator_type": "author", "first_name": "Ping", "last_name": "Dai", "name": null }, { "creator_type": "author", "first_name": "Hideo", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Tetsuro", "last_name": "Takamatsu", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/nmeth770" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "15973419" } }, "mesh": [ { "descriptor": "Connexin 43", "descriptor_ui": "D018031", "major_topic": false }, { "descriptor": "Fluorescent Dyes", "descriptor_ui": "D005456", "major_topic": false }, { "descriptor": "Gene Targeting", "descriptor_ui": "D018390", "major_topic": false }, { "descriptor": "Green Fluorescent Proteins", "descriptor_ui": "D049452", "major_topic": false }, { "descriptor": "HeLa Cells", "descriptor_ui": "D006367", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Lasers", "descriptor_ui": "D007834", "major_topic": true }, { "descriptor": "Microscopy, Confocal", "descriptor_ui": "D018613", "major_topic": false }, { "descriptor": "Microscopy, Fluorescence, Multiphoton", "descriptor_ui": "D036641", "major_topic": false }, { "descriptor": "Recombinant Fusion Proteins", "descriptor_ui": "D011993", "major_topic": false }, { "descriptor": "Staining and Labeling", "descriptor_ui": "D013194", "major_topic": false } ], "publication": { "conference_name": null, "date": "2005 Jul", "date_precision": "unknown", "issue": "7", "normalized_date": null, "pages": "503-505", "proceedings_title": null, "publisher": "", "title": "Nature methods", "volume": "2", "year": 2005 }, "ssbd": { "database": [], "repository": [] }, "title": "Multiphoton excitation-evoked chromophore-assisted laser inactivation using green fluorescent protein.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "In an attempt to disclose mechanisms of hepatocarcinogenesis and discover novel target molecules for the diagnosis and treatment of hepatocellular carcinomas (HCCs), we previously analyzed expression profiles of HCC tissues by means of human cDNA microarray. Among the genes upregulated in tumor tissues compared with their nontumor counterparts, we focused on a novel gene, termed WDRPUH, and characterized its biologic function. WDRPUH encodes a predicted 620-amino acid protein containing 11 highly conserved WD40-repeat domains. Multiple-tissue Northern blot analysis revealed its specific expression in the testis among 16 normal tissues examined. Transfection of plasmids designed to express WDRPUH-specific siRNA significantly reduced its expression in HCC cells and resulted in growth suppression of transfected cells. Interestingly, we found that WDRPUH associated with HSP70, proteins of the chaperonin-containing TCP-1 (CCT1) complex, as well as BRCA2. These findings have disclosed a novel insight into hepatocarcinogenesis and suggested that WDRPUH may be a molecular target for the development of new strategies to treat HCCs.", "classifications": [ { "id": "Hamamoto", "label": "Group Hamamoto", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Fabio Pittella", "last_name": "Silva", "name": null }, { "creator_type": "author", "first_name": "Ryuji", "last_name": "Hamamoto", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Yoichi", "last_name": "Furukawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1593/neo.04544" }, "pmcid": { "normalized": "PMC1501145" }, "pmid": { "normalized": "15967112" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Blotting, Northern", "descriptor_ui": "D015152", "major_topic": false }, { "descriptor": "BRCA2 Protein", "descriptor_ui": "D024682", "major_topic": false }, { "descriptor": "Carcinoma, Hepatocellular", "descriptor_ui": "D006528", "major_topic": false }, { "descriptor": "Carrier Proteins", "descriptor_ui": "D002352", "major_topic": false }, { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "Cell Line, Tumor", "descriptor_ui": "D045744", "major_topic": false }, { "descriptor": "Cell Proliferation", "descriptor_ui": "D049109", "major_topic": false }, { "descriptor": "Cell Survival", "descriptor_ui": "D002470", "major_topic": false }, { "descriptor": "Chaperonins", "descriptor_ui": "D018833", "major_topic": false }, { "descriptor": "Cilia", "descriptor_ui": "D002923", "major_topic": false }, { "descriptor": "Cloning, Molecular", "descriptor_ui": "D003001", "major_topic": false }, { "descriptor": "DNA, Complementary", "descriptor_ui": "D018076", "major_topic": false }, { "descriptor": "Gene Expression Regulation, Neoplastic", "descriptor_ui": "D015972", "major_topic": true }, { "descriptor": "Gene Silencing", "descriptor_ui": "D020868", "major_topic": false }, { "descriptor": "HSP70 Heat-Shock Proteins", "descriptor_ui": "D018840", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Immunoblotting", "descriptor_ui": "D015151", "major_topic": false }, { "descriptor": "Immunoprecipitation", "descriptor_ui": "D047468", "major_topic": false }, { "descriptor": "Liver Neoplasms", "descriptor_ui": "D008113", "major_topic": false }, { "descriptor": "Mass Spectrometry", "descriptor_ui": "D013058", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Microscopy, Fluorescence", "descriptor_ui": "D008856", "major_topic": false }, { "descriptor": "NIH 3T3 Cells", "descriptor_ui": "D041681", "major_topic": false }, { "descriptor": "Oligonucleotide Array Sequence Analysis", "descriptor_ui": "D020411", "major_topic": false }, { "descriptor": "Plasmids", "descriptor_ui": "D010957", "major_topic": false }, { "descriptor": "Protein Binding", "descriptor_ui": "D011485", "major_topic": false }, { "descriptor": "Protein Structure, Tertiary", "descriptor_ui": "D017434", "major_topic": false }, { "descriptor": "Reverse Transcriptase Polymerase Chain Reaction", "descriptor_ui": "D020133", "major_topic": false }, { "descriptor": "RNA", "descriptor_ui": "D012313", "major_topic": false }, { "descriptor": "RNA, Small Interfering", "descriptor_ui": "D034741", "major_topic": false }, { "descriptor": "Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization", "descriptor_ui": "D019032", "major_topic": false }, { "descriptor": "Tissue Distribution", "descriptor_ui": "D014018", "major_topic": false }, { "descriptor": "Transfection", "descriptor_ui": "D014162", "major_topic": false }, { "descriptor": "Up-Regulation", "descriptor_ui": "D015854", "major_topic": false } ], "publication": { "conference_name": null, "date": "2005 Apr", "date_precision": "unknown", "issue": "4", "normalized_date": null, "pages": "348-355", "proceedings_title": null, "publisher": "", "title": "Neoplasia (New York, N.Y.)", "volume": "7", "year": 2005 }, "ssbd": { "database": [], "repository": [] }, "title": "WDRPUH, a novel WD-repeat-containing protein, is highly expressed in human hepatocellular carcinoma and involved in cell proliferation.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Beta-arrestin mediates desensitization and internalization of beta-adrenergic receptors (betaARs), but also acts as a scaffold protein in extracellular signal-regulated kinase (ERK) cascade. Thus, we have examined the role of beta-arrestin2 in the betaAR-mediated ERK signaling pathways. Isoproterenol stimulation equally activated cytoplasmic and nuclear ERK in COS-7 cells expressing beta1AR or beta2AR. However, the activity of nuclear ERK was enhanced by co-expression of beta-arrestin2 in beta2AR-but not beta1AR-expressing cells. Pertussis toxin treatment and blockade of Gbetagamma action inhibited beta-arrestin2-enhanced nuclear activation of ERK, suggesting that beta-arrestin2 promotes nuclear ERK localization in a Gbetagamma dependent mechanism upon receptor stimulation. beta2AR containing the carboxyl terminal region of beta1AR lost the beta-arrestin2-promoted nuclear translocation. As the carboxyl terminal region is important for beta-arrestin binding, these results demonstrate that recruitment of beta-arrestin2 to carboxyl terminal region of beta2AR is important for ERK localization to the nucleus.", "classifications": [ { "id": "Nishida", "label": "Group Nishida", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Narita", "name": null }, { "creator_type": "author", "first_name": "Motohiro", "last_name": "Nishida", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Kurose", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.cellsig.2004.12.014" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "16038799" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Arrestins", "descriptor_ui": "D019390", "major_topic": false }, { "descriptor": "beta-Adrenergic Receptor Kinases", "descriptor_ui": "D051552", "major_topic": false }, { "descriptor": "beta-Arrestins", "descriptor_ui": "D000071557", "major_topic": false }, { "descriptor": "Cell Nucleus", "descriptor_ui": "D002467", "major_topic": false }, { "descriptor": "Chlorocebus aethiops", "descriptor_ui": "D002522", "major_topic": false }, { "descriptor": "COS Cells", "descriptor_ui": "D019556", "major_topic": false }, { "descriptor": "Cyclic AMP-Dependent Protein Kinases", "descriptor_ui": "D017868", "major_topic": false }, { "descriptor": "Cytoplasm", "descriptor_ui": "D003593", "major_topic": false }, { "descriptor": "Extracellular Signal-Regulated MAP Kinases", "descriptor_ui": "D048049", "major_topic": false }, { "descriptor": "Heterotrimeric GTP-Binding Proteins", "descriptor_ui": "D020962", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Isoproterenol", "descriptor_ui": "D007545", "major_topic": false }, { "descriptor": "Microscopy, Fluorescence", "descriptor_ui": "D008856", "major_topic": false }, { "descriptor": "Mitogen-Activated Protein Kinase 1", "descriptor_ui": "D019950", "major_topic": false }, { "descriptor": "Mitogen-Activated Protein Kinase 3", "descriptor_ui": "D048052", "major_topic": false }, { "descriptor": "Phosphorylation", "descriptor_ui": "D010766", "major_topic": false }, { "descriptor": "Protein Binding", "descriptor_ui": "D011485", "major_topic": false }, { "descriptor": "Protein Kinase Inhibitors", "descriptor_ui": "D047428", "major_topic": false }, { "descriptor": "Protein Transport", "descriptor_ui": "D021381", "major_topic": false }, { "descriptor": "Pyrimidines", "descriptor_ui": "D011743", "major_topic": false }, { "descriptor": "Receptors, Adrenergic, beta-1", "descriptor_ui": "D018342", "major_topic": false }, { "descriptor": "Receptors, Adrenergic, beta-2", "descriptor_ui": "D018343", "major_topic": false }, { "descriptor": "Recombinant Fusion Proteins", "descriptor_ui": "D011993", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "src-Family Kinases", "descriptor_ui": "D019061", "major_topic": false }, { "descriptor": "Transfection", "descriptor_ui": "D014162", "major_topic": false } ], "publication": { "conference_name": null, "date": "2005 Oct", "date_precision": "unknown", "issue": "10", "normalized_date": null, "pages": "1248-1253", "proceedings_title": null, "publisher": "", "title": "Cellular signalling", "volume": "17", "year": 2005 }, "ssbd": { "database": [], "repository": [] }, "title": "Beta-arrestin2 enhances beta2-adrenergic receptor-mediated nuclear translocation of ERK.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "We develop a compact scanning head for use in laser confocal fluorescence microscopy for in situ fluorescence imaging of organs. The head, cylindrical in shape, has 3.5 mm diameter and 30 mm length, and is thus small enough to operate in a living rat heart. The lateral and axial resolutions, defined as full widths at half maximum (FWHM) of a point spread function (PSF), measures 1.0 and 5.0 microm, respectively, for 488-nm excitation and 1.0 and 5.4 microm, respectively, for 543-nm excitation. The chromatic aberration between 488- and 543-nm laser beams is well suppressed. We perform Ca2+ imaging in cardiomyocytes through the right ventricular chamber of a perfused rat heart in line-scan mode with 2.9-ms time resolution. We also carried out two-color imaging of a fixed mouse heart and liver with subcellular resolution. The compact head of the microscope equipped with a line-scan imaging mode and two-color imaging mode is useful for in situ imaging in living organs with subcellular resolution and can advantageously be applied to in vivo research.", "classifications": [ { "id": "Tanaka", "label": "Group Tanaka", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Taisuke", "last_name": "Ota", "name": null }, { "creator_type": "author", "first_name": "Hiroya", "last_name": "Fukuyama", "name": null }, { "creator_type": "author", "first_name": "Yasushige", "last_name": "Ishihara", "name": null }, { "creator_type": "author", "first_name": "Hideo", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Tetsuro", "last_name": "Takamatsu", "name": null } ], "identifiers": { "doi": { "normalized": "10.1117/1.1890411" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "15910084" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Calcium", "descriptor_ui": "D002118", "major_topic": false }, { "descriptor": "Color", "descriptor_ui": "D003116", "major_topic": false }, { "descriptor": "Heart", "descriptor_ui": "D006321", "major_topic": false }, { "descriptor": "Heart Ventricles", "descriptor_ui": "D006352", "major_topic": false }, { "descriptor": "In Vitro Techniques", "descriptor_ui": "D066298", "major_topic": false }, { "descriptor": "Liver", "descriptor_ui": "D008099", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Microscopy, Confocal", "descriptor_ui": "D018613", "major_topic": false }, { "descriptor": "Microscopy, Fluorescence", "descriptor_ui": "D008856", "major_topic": true }, { "descriptor": "Myocytes, Cardiac", "descriptor_ui": "D032383", "major_topic": false }, { "descriptor": "Perfusion", "descriptor_ui": "D010477", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Rats, Wistar", "descriptor_ui": "D017208", "major_topic": false } ], "publication": { "conference_name": null, "date": "2005 Mar-Apr", "date_precision": "unknown", "issue": "2", "normalized_date": null, "pages": "024010", "proceedings_title": null, "publisher": "", "title": "Journal of biomedical optics", "volume": "10", "year": 2005 }, "ssbd": { "database": [], "repository": [] }, "title": "In situ fluorescence imaging of organs through compact scanning head for confocal laser microscopy.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Mammalian preimplantation development involves several crucial events, such as compaction and blastocyst formation, but little is known about essential genes that regulate this developmental process. Here, we have focused on MAP kinase signaling pathways as potential regulatory pathways for the process. Our results show that inhibition of the JNK pathway or of the p38 MAP kinase pathway, but not of the ERK pathway, results in inhibition of cavity formation, and that JNK and p38 are active during mouse preimplantation development. Our subsequent microarray analyses show that, of about 39,000 transcripts analyzed, the number of those genes whose expression level is sensitive to the inhibition of the JNK or the p38 pathway, but insensitive to the inhibition of the ERK pathway, is only 156. Moreover, of the 156 genes, expression of 10 genes (two genes upregulated and eight genes downregulated) is sensitive to either inhibition of the JNK or p38 pathways. These 10 genes include several genes known for their function in axis and pattern formation. Downregulation of some of the 10 genes simultaneously using siRNA leads to abnormality in cavity formation. Thus, this study has successfully narrowed down candidate genes of interest, detailed analysis of which will probably lead to elucidation of the molecular mechanism of preimplantation development.", "classifications": [ { "id": "Yamamoto", "label": "Group Yamamoto", "parent": "Toyoshima", "type": "group" }, { "id": "Toyoshima", "label": "Team Toyoshima", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Momoko", "last_name": "Maekawa", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Takuji", "last_name": "Tanoue", "name": null }, { "creator_type": "author", "first_name": "Yasuhito", "last_name": "Yuasa", "name": null }, { "creator_type": "author", "first_name": "Osamu", "last_name": "Chisaka", "name": null }, { "creator_type": "author", "first_name": "Eisuke", "last_name": "Nishida", "name": null } ], "identifiers": { "doi": { "normalized": "10.1242/dev.01729" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "15772134" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Blastocyst", "descriptor_ui": "D001755", "major_topic": false }, { "descriptor": "DNA Primers", "descriptor_ui": "D017931", "major_topic": false }, { "descriptor": "Gene Expression Regulation, Developmental", "descriptor_ui": "D018507", "major_topic": true }, { "descriptor": "Genes", "descriptor_ui": "D005796", "major_topic": false }, { "descriptor": "MAP Kinase Signaling System", "descriptor_ui": "D020935", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred ICR", "descriptor_ui": "D008813", "major_topic": false }, { "descriptor": "Microinjections", "descriptor_ui": "D008845", "major_topic": false }, { "descriptor": "Microscopy, Fluorescence", "descriptor_ui": "D008856", "major_topic": false }, { "descriptor": "Oligonucleotide Array Sequence Analysis", "descriptor_ui": "D020411", "major_topic": false }, { "descriptor": "Reverse Transcriptase Polymerase Chain Reaction", "descriptor_ui": "D020133", "major_topic": false }, { "descriptor": "RNA, Small Interfering", "descriptor_ui": "D034741", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false } ], "publication": { "conference_name": null, "date": "2005 Apr", "date_precision": "unknown", "issue": "8", "normalized_date": null, "pages": "1773-1783", "proceedings_title": null, "publisher": "", "title": "Development (Cambridge, England)", "volume": "132", "year": 2005 }, "ssbd": { "database": [], "repository": [] }, "title": "Requirement of the MAP kinase signaling pathways for mouse preimplantation development.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "To elucidate the hidden dynamics of extracellular-signal-regulated kinase (ERK) signalling networks, we developed a simulation model of ERK signalling networks by constraining in silico dynamics based on in vivo dynamics in PC12 cells. We predicted and validated that transient ERK activation depends on rapid increases of epidermal growth factor and nerve growth factor (NGF) but not on their final concentrations, whereas sustained ERK activation depends on the final concentration of NGF but not on the temporal rate of increase. These ERK dynamics depend on Ras and Rap1 dynamics, the inactivation processes of which are growth-factor-dependent and -independent, respectively. Therefore, the Ras and Rap1 systems capture the temporal rate and concentration of growth factors, and encode these distinct physical properties into transient and sustained ERK activation, respectively.", "classifications": [ { "id": "Kuroda", "label": "Group Kuroda", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Satoru", "last_name": "Sasagawa", "name": null }, { "creator_type": "author", "first_name": "Yu-ichi", "last_name": "Ozaki", "name": null }, { "creator_type": "author", "first_name": "Kazuhiro", "last_name": "Fujita", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Kuroda", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/ncb1233" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "15793571" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Computer Simulation", "descriptor_ui": "D003198", "major_topic": true }, { "descriptor": "Enzyme Activation", "descriptor_ui": "D004789", "major_topic": false }, { "descriptor": "Epidermal Growth Factor", "descriptor_ui": "D004815", "major_topic": false }, { "descriptor": "Extracellular Signal-Regulated MAP Kinases", "descriptor_ui": "D048049", "major_topic": false }, { "descriptor": "Kinetics", "descriptor_ui": "D007700", "major_topic": false }, { "descriptor": "Models, Biological", "descriptor_ui": "D008954", "major_topic": true }, { "descriptor": "Nerve Growth Factor", "descriptor_ui": "D020932", "major_topic": false }, { "descriptor": "PC12 Cells", "descriptor_ui": "D016716", "major_topic": false }, { "descriptor": "rap1 GTP-Binding Proteins", "descriptor_ui": "D020827", "major_topic": false }, { "descriptor": "ras Proteins", "descriptor_ui": "D018631", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Time Factors", "descriptor_ui": "D013997", "major_topic": false } ], "publication": { "conference_name": null, "date": "2005 Apr", "date_precision": "unknown", "issue": "4", "normalized_date": null, "pages": "365-373", "proceedings_title": null, "publisher": "", "title": "Nature cell biology", "volume": "7", "year": 2005 }, "ssbd": { "database": [], "repository": [] }, "title": "Prediction and validation of the distinct dynamics of transient and sustained ERK activation.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Cardiomyocytes express both beta(1)- and beta(2)-adrenergic receptors, and these receptors play a differential role in chronotropic and inotropic effects of the heart. Caveolae are known as an important regulator of G-protein-coupled receptor signaling. In the present report, we examined whether caveolae have a role in beta-adrenergic receptor-stimulated cAMP production and protein kinase A activation in neonatal myocytes. Isoproterenol-stimulated cAMP production was mediated by beta(1)- and beta(2)-subtypes, which depends on the receptor number of each subtype. However, protein kinase A activation was exclusively mediated by the beta(1)-subtype. Disruption of caveolae by methyl-beta-cyclodextrin treatment did not affect the relative contribution of subtypes to isoproterenol-stimulated cAMP production. beta(1)-Subtype-mediated protein kinase A activation was also not affected by the disruption of caveolae. These results suggest that beta(1)-adrenergic receptor-mediated protein kinase A activation is compartmentalized and independent of caveolae.", "classifications": [ { "id": "Nishida", "label": "Group Nishida", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Masashi", "last_name": "Fukutomi", "name": null }, { "creator_type": "author", "first_name": "Motohiro", "last_name": "Nishida", "name": null }, { "creator_type": "author", "first_name": "Yoshiko", "last_name": "Maruyama", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Kurose", "name": null } ], "identifiers": { "doi": { "normalized": "10.1254/jphs.fp0050244" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "15942126" } }, "mesh": [ { "descriptor": "Adrenergic beta-Agonists", "descriptor_ui": "D000318", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Animals, Newborn", "descriptor_ui": "D000831", "major_topic": false }, { "descriptor": "Caveolae", "descriptor_ui": "D021941", "major_topic": false }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Cyclic AMP", "descriptor_ui": "D000242", "major_topic": false }, { "descriptor": "Cyclic AMP-Dependent Protein Kinases", "descriptor_ui": "D017868", "major_topic": false }, { "descriptor": "Enzyme Activation", "descriptor_ui": "D004789", "major_topic": false }, { "descriptor": "Isoproterenol", "descriptor_ui": "D007545", "major_topic": false }, { "descriptor": "Myocardium", "descriptor_ui": "D009206", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Rats, Sprague-Dawley", "descriptor_ui": "D017207", "major_topic": false }, { "descriptor": "Receptors, Adrenergic, beta-1", "descriptor_ui": "D018342", "major_topic": false }, { "descriptor": "Receptors, Adrenergic, beta-2", "descriptor_ui": "D018343", "major_topic": false } ], "publication": { "conference_name": null, "date": "2005 Jun", "date_precision": "unknown", "issue": "2", "normalized_date": null, "pages": "168-174", "proceedings_title": null, "publisher": "", "title": "Journal of pharmacological sciences", "volume": "98", "year": 2005 }, "ssbd": { "database": [], "repository": [] }, "title": "Caveolae-independent activation of protein kinase A in rat neonatal myocytes.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "We have isolated a mouse cDNA for a novel dual-specificity phosphatase designated LDP-3 (low-molecular-mass dual-specificity phosphatase 3). The 450 bp open reading frame encodes a protein of 150 amino acids with a predicted molecular mass of 16 kDa. Northern blot and reverse transcription–PCR analyses show that LDP-3 transcripts are expressed in almost all mouse tissues examined. In vitro analyses using several substrates and inhibitors indicate that LDP-3 possesses intrinsic dual-specificity phosphatase activity. When expressed in mammalian cells, LDP-3 protein is localized mainly to the apical submembrane area. Forced expression of LDP-3 does not alter activation of ERK (extracellular-signal-regulated kinase), but rather enhances activation of JNK (c-Jun N-terminal kinase) and p38 and their respective upstream kinases MKK4 (mitogen-activated protein kinase kinase 4) and MKK6 in cells treated with 0.4 M sorbitol. By screening with a variety of stimuli, we found that LDP-3 specifically enhances the osmotic stress-induced activation of JNK and p38.", "classifications": [ { "id": "Takekawa", "label": "Group Takekawa", "parent": "Takekawa", "type": "group" }, { "id": "Takekawa", "label": "Team Takekawa", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Kentaro", "last_name": "Takagaki", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Satoh", "name": null }, { "creator_type": "author", "first_name": "Nobuhiro", "last_name": "Tanuma", "name": null }, { "creator_type": "author", "first_name": "Kouhei", "last_name": "Masuda", "name": null }, { "creator_type": "author", "first_name": "Mutsuhiro", "last_name": "Takekawa", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Shima", "name": null }, { "creator_type": "author", "first_name": "Kunimi", "last_name": "Kikuchi", "name": null } ], "identifiers": { "doi": { "normalized": "10.1042/bj20040498" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "15281913" } }, "mesh": [ { "descriptor": "Amino Acid Sequence", "descriptor_ui": "D000595", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "Chlorocebus aethiops", "descriptor_ui": "D002522", "major_topic": false }, { "descriptor": "COS Cells", "descriptor_ui": "D019556", "major_topic": false }, { "descriptor": "Dual-Specificity Phosphatases", "descriptor_ui": "D054637", "major_topic": false }, { "descriptor": "Enzyme Activation", "descriptor_ui": "D004789", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "JNK Mitogen-Activated Protein Kinases", "descriptor_ui": "D048031", "major_topic": false }, { "descriptor": "MAP Kinase Kinase Kinase 4", "descriptor_ui": "D048768", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mitogen-Activated Protein Kinase 6", "descriptor_ui": "D048053", "major_topic": false }, { "descriptor": "Molecular Sequence Data", "descriptor_ui": "D008969", "major_topic": false }, { "descriptor": "Molecular Weight", "descriptor_ui": "D008970", "major_topic": false }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": false }, { "descriptor": "Osmotic Pressure", "descriptor_ui": "D009997", "major_topic": false }, { "descriptor": "p38 Mitogen-Activated Protein Kinases", "descriptor_ui": "D048051", "major_topic": false }, { "descriptor": "Protein Tyrosine Phosphatases", "descriptor_ui": "D017027", "major_topic": false }, { "descriptor": "Substrate Specificity", "descriptor_ui": "D013379", "major_topic": false }, { "descriptor": "Transfection", "descriptor_ui": "D014162", "major_topic": false } ], "publication": { "conference_name": null, "date": "2004 Nov 1", "date_precision": "day", "issue": "Pt 3", "normalized_date": "2004-11-01", "pages": "447-455", "proceedings_title": null, "publisher": "", "title": "Biochemical Journal", "volume": "383", "year": 2004 }, "ssbd": { "database": [], "repository": [] }, "title": "Characterization of a novel low-molecular-mass dual-specificity phosphatase-3 (LDP-3) that enhances activation of JNK and p38.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Stochasticity is an intrinsic property of genetic regulatory networks due to the low copy numbers of the major molecular species, such as, DNA, mRNA, and regulatory proteins. Therefore, investigation of the mechanisms that reduce the stochastic noise is essential in understanding the reproducible behaviors of real organisms and is also a key to design synthetic genetic regulatory networks that can reliably work. We use an analytical and systematic method, the linear noise approximation of the chemical master equation along with the decoupling of a stoichiometric matrix. In the analysis of fluctuations of multiple molecular species, the covariance is an important measure of noise. However, usually the representation of a covariance matrix in the natural coordinate system, i.e. the copy numbers of the molecular species, is intractably complicated because reactions change copy numbers of more than one molecular species simultaneously. Decoupling of a stoichiometric matrix, which is a transformation of variables, significantly simplifies the representation of a covariance matrix and elucidates the mechanisms behind the observed fluctuations in the copy numbers. We apply our method to three types of fundamental genetic regulatory networks, that is, a single-gene autoregulatory network, a two-gene autoregulatory network, and a mutually repressive network. We have found that there are multiple noise components differently originating. Each noise component produces fluctuation in the characteristic direction. The resulting fluctuations in the copy numbers of the molecular species are the sum of these fluctuations. In the examples, the limitation of the negative feedback in noise reduction and the trade-off of fluctuations in multiple molecular species are clearly explained. The analytical representations show the full parameter dependence. Additionally, the validity of our method is tested by stochastic simulations.", "classifications": [ { "id": "Kobayashi", "label": "Group Kobayashi", "parent": "Wakamoto", "type": "group" }, { "id": "Wakamoto", "label": "Team Wakamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Ryota", "last_name": "Tomioka", "name": null }, { "creator_type": "author", "first_name": "Hidenori", "last_name": "Kimura", "name": null }, { "creator_type": "author", "first_name": "Tetsuya", "last_name": "J Kobayashi", "name": null }, { "creator_type": "author", "first_name": "Kazuyuki", "last_name": "Aihara", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.jtbi.2004.04.034" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "15246787" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Gene Expression Regulation", "descriptor_ui": "D005786", "major_topic": true }, { "descriptor": "Homeostasis", "descriptor_ui": "D006706", "major_topic": false }, { "descriptor": "Models, Genetic", "descriptor_ui": "D008957", "major_topic": true }, { "descriptor": "Multivariate Analysis", "descriptor_ui": "D015999", "major_topic": false }, { "descriptor": "Stochastic Processes", "descriptor_ui": "D013269", "major_topic": false } ], "publication": { "conference_name": null, "date": "2004 Aug 21", "date_precision": "day", "issue": "4", "normalized_date": "2004-08-21", "pages": "501-521", "proceedings_title": null, "publisher": "", "title": "Journal of theoretical biology", "volume": "229", "year": 2004 }, "ssbd": { "database": [], "repository": [] }, "title": "Multivariate analysis of noise in genetic regulatory networks.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "After ipsilateral injections of biotinylated dextran amine (BDA) into the central nucleus of the amygdala (ACe) and cholera toxin B subunit (CTb) into the motor trigeminal nucleus (Vm) in the rat, numerous BDA-labeled axons with bouton-like varicosities were distributed bilaterally with a clear-cut ipsilateral dominance in the parvicellular reticular formation (RFp), where many CTb-labeled neurons existed bilaterally with slightly ipsilateral dominance. The prominent overlapping distribution of these labeled axons and neurons was found in the RFp region just ventral to the nucleus of the solitary tract and medial to the spinal trigeminal nucleus throughout the caudalmost part of the pons and the rostral half of the medulla oblongata. Within the neuropil of the RFp region in the rostral half of the medulla oblongata, BDA-labeled axons made symmetrical synaptic contacts predominantly with the dendrites and additionally with the somata of RFp neurons, some of which were labeled with CTb. These data suggest that output signals from the ACe may be transmitted disynaptically to the Vm via the RFp neurons in the medulla oblongata for the control of jaw movements.", "classifications": [ { "id": "Yokota", "label": "Group Yokota", "parent": "Enomoto", "type": "group" }, { "id": "Enomoto", "label": "Team Enomoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yukihiko", "last_name": "Yasui", "name": null }, { "creator_type": "author", "first_name": "Toshiko", "last_name": "Tsumori", "name": null }, { "creator_type": "author", "first_name": "Tatsuro", "last_name": "Oka", "name": null }, { "creator_type": "author", "first_name": "Shigefumi", "last_name": "Yokota", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.brainres.2004.04.080" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "15234261" } }, "mesh": [ { "descriptor": "Amygdala", "descriptor_ui": "D000679", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Biotin", "descriptor_ui": "D001710", "major_topic": false }, { "descriptor": "Cholera Toxin", "descriptor_ui": "D002772", "major_topic": false }, { "descriptor": "Dextrans", "descriptor_ui": "D003911", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Medulla Oblongata", "descriptor_ui": "D008526", "major_topic": false }, { "descriptor": "Microscopy, Electron", "descriptor_ui": "D008854", "major_topic": false }, { "descriptor": "Neural Pathways", "descriptor_ui": "D009434", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Presynaptic Terminals", "descriptor_ui": "D017729", "major_topic": true }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Rats, Wistar", "descriptor_ui": "D017208", "major_topic": false }, { "descriptor": "Reticular Formation", "descriptor_ui": "D012154", "major_topic": false }, { "descriptor": "Trigeminal Nuclei", "descriptor_ui": "D014278", "major_topic": false } ], "publication": { "conference_name": null, "date": "2004 Jul 30", "date_precision": "day", "issue": "1", "normalized_date": "2004-07-30", "pages": "129-134", "proceedings_title": null, "publisher": "", "title": "Brain research", "volume": "1016", "year": 2004 }, "ssbd": { "database": [], "repository": [] }, "title": "Amygdaloid axon terminals are in contact with trigeminal premotor neurons in the parvicellular reticular formation of the rat medulla oblongata.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Tob, a member of the Tob and BTG antiproliferative protein family, plays an important role in many cellular processes including cell proliferation. In this study, we have addressed molecular mechanisms regulating subcellular localization of Tob. Treatment with leptomycin B, an inhibitor of nuclear export signal (NES) receptor, resulted in a change in subcellular distribution of Tob from its pan-cellular distribution to nuclear accumulation, indicating the existence of NES in Tob. Our results have then identified an N-terminal region (residues 2-14) of Tob as a functional NES. They have also shown that Tob has a functional, bipartite nuclear localization signal (NLS) in residues 18-40. Thus, Tob is shuttling between the nucleus and the cytoplasm by its NES and NLS. To examine a possible relationship between subcellular distribution of Tob and its function, we exogenously added a strong NLS sequence or a strong NES sequence or both to Tob. The obtained results have demonstrated that the strong NLS-added Tob has a much weaker activity to inhibit cell cycle progression from G0/G1 to S phase. These results suggest that cytoplasmic localization or nucleocytoplasmic shuttling is important for the antiproliferative function of Tob.", "classifications": [ { "id": "Yamamoto", "label": "Group Yamamoto", "parent": "Toyoshima", "type": "group" }, { "id": "Toyoshima", "label": "Team Toyoshima", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Momoko", "last_name": "Maekawa", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Eisuke", "last_name": "Nishida", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.yexcr.2003.12.016" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "15051490" } }, "mesh": [ { "descriptor": "3T3 Cells", "descriptor_ui": "D016475", "major_topic": false }, { "descriptor": "Active Transport, Cell Nucleus", "descriptor_ui": "D021581", "major_topic": false }, { "descriptor": "Amino Acid Sequence", "descriptor_ui": "D000595", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Brain", "descriptor_ui": "D001921", "major_topic": false }, { "descriptor": "Carrier Proteins", "descriptor_ui": "D002352", "major_topic": false }, { "descriptor": "DNA Primers", "descriptor_ui": "D017931", "major_topic": false }, { "descriptor": "Gene Library", "descriptor_ui": "D015723", "major_topic": false }, { "descriptor": "Genes, Tumor Suppressor", "descriptor_ui": "D016147", "major_topic": false }, { "descriptor": "Genetic Vectors", "descriptor_ui": "D005822", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Intracellular Signaling Peptides and Proteins", "descriptor_ui": "D047908", "major_topic": true }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Molecular Sequence Data", "descriptor_ui": "D008969", "major_topic": false }, { "descriptor": "Mutagenesis, Site-Directed", "descriptor_ui": "D016297", "major_topic": false }, { "descriptor": "Peptide Fragments", "descriptor_ui": "D010446", "major_topic": false }, { "descriptor": "Polymerase Chain Reaction", "descriptor_ui": "D016133", "major_topic": false }, { "descriptor": "Recombinant Proteins", "descriptor_ui": "D011994", "major_topic": false }, { "descriptor": "Sequence Alignment", "descriptor_ui": "D016415", "major_topic": false }, { "descriptor": "Sequence Homology, Amino Acid", "descriptor_ui": "D017386", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Transfection", "descriptor_ui": "D014162", "major_topic": false }, { "descriptor": "Tumor Suppressor Proteins", "descriptor_ui": "D025521", "major_topic": true } ], "publication": { "conference_name": null, "date": "2004 Apr 15", "date_precision": "day", "issue": "1", "normalized_date": "2004-04-15", "pages": "59-65", "proceedings_title": null, "publisher": "", "title": "Experimental cell research", "volume": "295", "year": 2004 }, "ssbd": { "database": [], "repository": [] }, "title": "Regulation of subcellular localization of the antiproliferative protein Tob by its nuclear export signal and bipartite nuclear localization signal sequences.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The stress-inducible molecules GADD45β and GADD45γ have been implicated in regulating IFNγ production in CD4 T cells. However, how GADD45 proteins function has been controversial. MEKK4 is a MAP kinase kinase kinase that interacts with GADD45 in vitro. Here we generated MEKK4-deficient mice to define the function and regulation of this pathway. CD4 T cells from MEKK4−/− mice have reduced p38 activity and defective IFNγ synthesis. Expression of GADD45β or GADD45γ promotes IFNγ production in MEKK4+/+ T cells, but not in MEKK4−/− cells or in cells treated with a p38 inhibitor. Thus, MEKK4 mediates the action of GADD45β and GADD45γ on p38 activation and IFNγ production. During Th1 differentiation, the GADD45β/GADD45γ/MEKK4 pathway appears to integrate upstream signals transduced by both T cell receptor and IL12/STAT4, leading to augmented IFNγ production in a process independent of STAT4.", "classifications": [ { "id": "Takekawa", "label": "Group Takekawa", "parent": "Takekawa", "type": "group" }, { "id": "Takekawa", "label": "Team Takekawa", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Hongbo", "last_name": "Chi", "name": null }, { "creator_type": "author", "first_name": "Binfeng", "last_name": "Lu", "name": null }, { "creator_type": "author", "first_name": "Mutsuhiro", "last_name": "Takekawa", "name": null }, { "creator_type": "author", "first_name": "Roger J.", "last_name": "Davis", "name": null }, { "creator_type": "author", "first_name": "Richard A.", "last_name": "Flavell", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/sj.emboj.7600173" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "15044949" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Antigens, Differentiation", "descriptor_ui": "D000943", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "DNA-Binding Proteins", "descriptor_ui": "D004268", "major_topic": false }, { "descriptor": "Enzyme Activation", "descriptor_ui": "D004789", "major_topic": false }, { "descriptor": "GADD45 Proteins", "descriptor_ui": "D000097642", "major_topic": false }, { "descriptor": "Gene Expression Regulation", "descriptor_ui": "D005786", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Interferon-gamma", "descriptor_ui": "D007371", "major_topic": false }, { "descriptor": "Intracellular Signaling Peptides and Proteins", "descriptor_ui": "D047908", "major_topic": false }, { "descriptor": "MAP Kinase Kinase Kinase 4", "descriptor_ui": "D048768", "major_topic": false }, { "descriptor": "MAP Kinase Signaling System", "descriptor_ui": "D020935", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred BALB C", "descriptor_ui": "D008807", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Knockout", "descriptor_ui": "D018345", "major_topic": false }, { "descriptor": "p38 Mitogen-Activated Protein Kinases", "descriptor_ui": "D048051", "major_topic": false }, { "descriptor": "STAT4 Transcription Factor", "descriptor_ui": "D050797", "major_topic": false }, { "descriptor": "Th1 Cells", "descriptor_ui": "D018417", "major_topic": false }, { "descriptor": "Trans-Activators", "descriptor_ui": "D015534", "major_topic": false } ], "publication": { "conference_name": null, "date": "2004 Apr 7", "date_precision": "day", "issue": "7", "normalized_date": "2004-04-07", "pages": "1576-1586", "proceedings_title": null, "publisher": "", "title": "The EMBO Journal", "volume": "23", "year": 2004 }, "ssbd": { "database": [], "repository": [] }, "title": "GADD45β/GADD45γ and MEKK4 comprise a genetic pathway mediating STAT4-independent IFNγ production in T cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "We have developed an integrated database that is specialized for the study of imprinted disease genes. The database contains novel candidate imprinted genes identified by the RIKEN full-length mouse cDNA microarray study, information on validated single nucleotide polymorphisms (SNPs) to confirm imprinting using reciprocal mouse crosses and the predicted physical position of imprinting-related disease loci in the mouse and human genomes. It has two user-friendly search interfaces: the SNP-central view (MuSCAT: MoUse SNP CATalog) and the candidate gene-central view (CITE: Candidate Imprinted Transcripts by Expression). The database, EICO (Expression-based Imprint Candidate Organizer), can be accessed via the World Wide Web (http://fantom2.gsc.riken.jp/EICODB/) and the DAS client software. These data and interfaces facilitate understanding of the mechanism of imprinting in mammalian inherited traits.", "classifications": [ { "id": "Nikaido", "label": "Group Nikaido", "parent": "Fujiwara", "type": "group" }, { "id": "Fujiwara", "label": "Team Fujiwara", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Itoshi", "last_name": "Nikaido", "name": null }, { "creator_type": "author", "first_name": "Chika", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Akiko", "last_name": "Wakamoto", "name": null }, { "creator_type": "author", "first_name": "Yasuhiro", "last_name": "Tomaru", "name": null }, { "creator_type": "author", "first_name": "Takahiro", "last_name": "Arakawa", "name": null }, { "creator_type": "author", "first_name": "Yoshihide", "last_name": "Hayashizaki", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Okazaki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1093/nar/gkh093" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "14681478" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Databases, Genetic", "descriptor_ui": "D030541", "major_topic": true }, { "descriptor": "Disease", "descriptor_ui": "D004194", "major_topic": true }, { "descriptor": "DNA, Complementary", "descriptor_ui": "D018076", "major_topic": false }, { "descriptor": "Genetics, Medical", "descriptor_ui": "D005826", "major_topic": false }, { "descriptor": "Genome", "descriptor_ui": "D016678", "major_topic": false }, { "descriptor": "Genomic Imprinting", "descriptor_ui": "D018392", "major_topic": false }, { "descriptor": "Genomics", "descriptor_ui": "D023281", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Information Storage and Retrieval", "descriptor_ui": "D016247", "major_topic": false }, { "descriptor": "Internet", "descriptor_ui": "D020407", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Oligonucleotide Array Sequence Analysis", "descriptor_ui": "D020411", "major_topic": false }, { "descriptor": "Polymorphism, Single Nucleotide", "descriptor_ui": "D020641", "major_topic": false }, { "descriptor": "Software", "descriptor_ui": "D012984", "major_topic": false }, { "descriptor": "User-Computer Interface", "descriptor_ui": "D014584", "major_topic": false } ], "publication": { "conference_name": null, "date": "2004 Jan 1", "date_precision": "day", "issue": "Database issue", "normalized_date": "2004-01-01", "pages": "D548-551", "proceedings_title": null, "publisher": "", "title": "Nucleic Acids Research", "volume": "32", "year": 2004 }, "ssbd": { "database": [], "repository": [] }, "title": "EICO (Expression-based Imprint Candidate Organizer): finding disease-related imprinted genes.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "We investigated quantitative changes over time in ultrasound signal intensity (an index of stiffness), signal duration (an index of surface irregularity), and interval between signals (an index of thickness) of plug cartilage in an animal model of autologous osteochondral grafting. A full-thickness osteochondral plug was surgically removed and replaced in male Japanese white rabbits (n = 22). Specimens obtained at day 0 and weeks 2, 4, 8, 12 and 24 postoperatively were assessed using an ultrasound system and by macroscopic and histological evaluation (modified Mankin's score). Histology revealed that the plug sank until 2 weeks postoperatively, and that newly formed cartilage-like tissue covered the plug, but at 24 weeks the tissue detached. The plug itself survived well throughout the period of observation. Although the signal intensity at the plug site was same as that in the sham operated contralateral knee at day 0, from 2 to 24 weeks postoperatively it was less than that in the sham knee. At 8 weeks, this difference was significant (P < 0.05). Modified Mankin's score revealed early degenerative changes at the site, but macroscopic examination did not. Signal intensity correlated significantly with score (both at day 0 and at the five postoperative time points [P < 0.05, r = -0.91] and as a whole [P < 0.05, r = -0.36]). Signal intensity also significantly correlated with the individual subscores for 'cartilage structure' (P < 0.05, r = -0.32) and 'cartilage cells' (P < 0.05, r = -0.30) from the modified Mankin's score, but not significantly with subscores for 'staining' and 'tidemark'. Signal duration correlated significantly with total score (as a whole [P < 0.05, r = 0.34]), but not significantly with the score for cartilage structure (P = 0.0557, r = 0.29). The interval between signals reflected well the actual thickness of the plug site. The significant relationships between ultrasound signal intensity and scores suggest that early degenerative changes in plug cartilage and cartilage-like tissue, especially in the superficial layer, are detectable by high-frequency ultrasound assessment.", "classifications": [ { "id": "Suzuki", "label": "Group Suzuki", "parent": "Takekawa", "type": "group" }, { "id": "Takekawa", "label": "Team Takekawa", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Kuroki", "name": null }, { "creator_type": "author", "first_name": "Yasuaki", "last_name": "Nakagawa", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Mori", "name": null }, { "creator_type": "author", "first_name": "Mao", "last_name": "Ohba", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Yasuyuki", "last_name": "Mizuno", "name": null }, { "creator_type": "author", "first_name": "Keiji", "last_name": "Ando", "name": null }, { "creator_type": "author", "first_name": "Makoto", "last_name": "Takenaka", "name": null }, { "creator_type": "author", "first_name": "Ken", "last_name": "Ikeuchi", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Nakamura", "name": null } ], "identifiers": { "doi": { "normalized": "10.1186/ar1219" }, "pmcid": { "normalized": "PMC1064862" }, "pmid": { "normalized": "15535827" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cartilage, Articular", "descriptor_ui": "D002358", "major_topic": false }, { "descriptor": "Knee Joint", "descriptor_ui": "D007719", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Models, Animal", "descriptor_ui": "D023421", "major_topic": false }, { "descriptor": "Pliability", "descriptor_ui": "D018583", "major_topic": false }, { "descriptor": "Rabbits", "descriptor_ui": "D011817", "major_topic": false }, { "descriptor": "Random Allocation", "descriptor_ui": "D011897", "major_topic": false }, { "descriptor": "Severity of Illness Index", "descriptor_ui": "D012720", "major_topic": false }, { "descriptor": "Transplantation, Autologous", "descriptor_ui": "D014182", "major_topic": false }, { "descriptor": "Ultrasonography", "descriptor_ui": "D014463", "major_topic": false }, { "descriptor": "Wound Healing", "descriptor_ui": "D014945", "major_topic": false } ], "publication": { "conference_name": null, "date": "2004", "date_precision": "year", "issue": "6", "normalized_date": "2004", "pages": "R492-504", "proceedings_title": null, "publisher": "", "title": "Arthritis research & therapy", "volume": "6", "year": 2004 }, "ssbd": { "database": [], "repository": [] }, "title": "Acoustic stiffness and change in plug cartilage over time after autologous osteochondral grafting: correlation between ultrasound signal intensity and histological score in a rabbit model.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Spatiotemporal control of the Ras/ERK MAP kinase signaling pathway is among the key mechanisms for regulating a wide variety of cellular processes. In this study, we report that human Sef (hSef), a recently identified inhibitor whose action mechanism has not been fully defined, acts as a molecular switch for ERK signaling by specifically blocking ERK nuclear translocation without inhibiting its activity in the cytoplasm. Thus, hSef binds to activated forms of MEK, inhibits the dissociation of the MEK-ERK complex, and blocks nuclear translocation of activated ERK. Consequently, hSef inhibits phosphorylation and activation of the nuclear ERK substrate Elk-1, while it does not affect phosphorylation of the cytoplasmic ERK substrate RSK2. Downregulation of endogenous hSef by hSef siRNA enhances the stimulus-induced ERK nuclear translocation and the activity of Elk-1. These results thus demonstrate that hSef acts as a spatial regulator for ERK signaling by targeting ERK to the cytoplasm.", "classifications": [ { "id": "Yamamoto", "label": "Group Yamamoto", "parent": "Toyoshima", "type": "group" }, { "id": "Toyoshima", "label": "Team Toyoshima", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Satoru", "last_name": "Torii", "name": null }, { "creator_type": "author", "first_name": "Morioh", "last_name": "Kusakabe", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Momoko", "last_name": "Maekawa", "name": null }, { "creator_type": "author", "first_name": "Eisuke", "last_name": "Nishida", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.devcel.2004.05.019" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "15239952" } }, "mesh": [ { "descriptor": "Active Transport, Cell Nucleus", "descriptor_ui": "D021581", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Nucleus", "descriptor_ui": "D002467", "major_topic": false }, { "descriptor": "Chlorocebus aethiops", "descriptor_ui": "D002522", "major_topic": false }, { "descriptor": "COS Cells", "descriptor_ui": "D019556", "major_topic": false }, { "descriptor": "Cytoplasm", "descriptor_ui": "D003593", "major_topic": false }, { "descriptor": "DNA-Binding Proteins", "descriptor_ui": "D004268", "major_topic": false }, { "descriptor": "ets-Domain Protein Elk-1", "descriptor_ui": "D050807", "major_topic": false }, { "descriptor": "HeLa Cells", "descriptor_ui": "D006367", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "MAP Kinase Kinase 1", "descriptor_ui": "D048369", "major_topic": false }, { "descriptor": "MAP Kinase Signaling System", "descriptor_ui": "D020935", "major_topic": false }, { "descriptor": "Mitogen-Activated Protein Kinase Kinases", "descriptor_ui": "D020929", "major_topic": false }, { "descriptor": "Mitogen-Activated Protein Kinases", "descriptor_ui": "D020928", "major_topic": false }, { "descriptor": "Phosphorylation", "descriptor_ui": "D010766", "major_topic": false }, { "descriptor": "Protein Transport", "descriptor_ui": "D021381", "major_topic": false }, { "descriptor": "Proto-Oncogene Proteins", "descriptor_ui": "D011518", "major_topic": false }, { "descriptor": "ras Proteins", "descriptor_ui": "D018631", "major_topic": false }, { "descriptor": "Receptors, Interleukin", "descriptor_ui": "D018123", "major_topic": false }, { "descriptor": "Ribosomal Protein S6 Kinases, 90-kDa", "descriptor_ui": "D038744", "major_topic": false }, { "descriptor": "Transcription Factors", "descriptor_ui": "D014157", "major_topic": false } ], "publication": { "conference_name": null, "date": "2004 Jul", "date_precision": "unknown", "issue": "1", "normalized_date": null, "pages": "33-44", "proceedings_title": null, "publisher": "", "title": "Developmental cell", "volume": "7", "year": 2004 }, "ssbd": { "database": [], "repository": [] }, "title": "Sef is a spatial regulator for Ras/MAP kinase signaling.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "We propose an approach designed to reconstitute a metabolic pathway composed of multistep biochemical reactions, rather than to dissect the individual reactions that make up the pathway. A synthetic in vitro glycolysis was reconstructed from ten purified Escherichia coli (E. coli) enzymes to obtain a better understanding of the regulation of sequential enzymatic reactions. The key to the success of this approach is the ability to perform direct and simultaneous determination of the diverse metabolic intermediates in the pathway by capillary electrophoresis-mass spectrometry. We observed that the pathway is regulated by a delicate balance between the changing metabolite concentrations and behaves like a natural biological oscillating network that has hitherto not been reported for E. coli glycolysis. The end-product, pyruvate, was periodically synthesized from glucose at an overall efficiency of 30%, corresponding to an average of 90% conversion efficiency for each of the ten steps involved. This approach is likely useful for the synthesis of natural products requiring complex sequential biocatalytic reactions.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Aya", "last_name": "Itoh", "name": null }, { "creator_type": "author", "first_name": "Yoshiaki", "last_name": "Ohashi", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Hirotada", "last_name": "Mori", "name": null }, { "creator_type": "author", "first_name": "Takaaki", "last_name": "Nishioka", "name": null }, { "creator_type": "author", "first_name": "Masaru", "last_name": "Tomita", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/elps.200305905" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "15237399" } }, "mesh": [ { "descriptor": "Catalysis", "descriptor_ui": "D002384", "major_topic": false }, { "descriptor": "Cloning, Molecular", "descriptor_ui": "D003001", "major_topic": false }, { "descriptor": "Electrophoresis, Capillary", "descriptor_ui": "D019075", "major_topic": false }, { "descriptor": "Escherichia coli", "descriptor_ui": "D004926", "major_topic": false }, { "descriptor": "Gene Expression", "descriptor_ui": "D015870", "major_topic": false }, { "descriptor": "Genetic Engineering", "descriptor_ui": "D005818", "major_topic": false }, { "descriptor": "Glucose", "descriptor_ui": "D005947", "major_topic": false }, { "descriptor": "Glycolysis", "descriptor_ui": "D006019", "major_topic": true }, { "descriptor": "Mass Spectrometry", "descriptor_ui": "D013058", "major_topic": false }, { "descriptor": "Pyruvic Acid", "descriptor_ui": "D019289", "major_topic": false }, { "descriptor": "Recombinant Proteins", "descriptor_ui": "D011994", "major_topic": false }, { "descriptor": "Sequence Analysis, DNA", "descriptor_ui": "D017422", "major_topic": false }, { "descriptor": "Time Factors", "descriptor_ui": "D013997", "major_topic": false } ], "publication": { "conference_name": null, "date": "2004 Jul", "date_precision": "unknown", "issue": "13", "normalized_date": null, "pages": "1996-2002", "proceedings_title": null, "publisher": "", "title": "Electrophoresis", "volume": "25", "year": 2004 }, "ssbd": { "database": [], "repository": [] }, "title": "Application of capillary electrophoresis-mass spectrometry to synthetic in vitro glycolysis studies.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Because reactive nitrogen species (RNS) have potent inflammatory activity, they may be involved in the inflammatory process in pulmonary diseases. We recently reported increased numbers of 3-nitrotyrosine immunopositive cells, which are evidences of RNS production, in the sputum of patients with chronic obstructive pulmonary disease (COPD) and patients with asthma compared with healthy subjects. In the present study, we attempted to quantify this protein nitration in the airways by means of high-performance liquid chromatography (HPLC) used together with an electrochemical detection system that we developed. Sputum samples were obtained from 15 stable COPD patients, 9 asthmatic patients and 7 healthy subjects by using hypertonic saline inhalation. The values for the molar ratio of protein-bound 3-nitrotyrosine/tyrosine in patients with asthma (4.31 +/- 1.13 x 10(-6), p < 0.05) and patients with COPD (3.04 +/- 0.36 x 10(-6), p < 0.01) were significantly higher than those in healthy subjects (1.37 +/- 0.19 x 10(-6)). The levels of protein-bound 3-nitrotyrosine in the airways were not significantly different in asthmatic patients and COPD patients. A significant negative correlation was found between values for protein-bound 3-nitrotyrosine/tyrosine and % FEV1 values in patients with COPD (r = -0.53, p < 0.05) but not in patients with asthma. These results suggest that our HPLC-electrochemical method is useful for quantifying RNS production in human airways. More importantly, they show that increased RNS production in the airways seems to contribute in a critical way to the pathogenesis of COPD, and that the effects of RNS in airways may differ in asthma and COPD.", "classifications": [ { "id": "Akaike", "label": "Group Akaike", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Hisatoshi", "last_name": "Sugiura", "name": null }, { "creator_type": "author", "first_name": "Masakazu", "last_name": "Ichinose", "name": null }, { "creator_type": "author", "first_name": "Masafumi", "last_name": "Tomaki", "name": null }, { "creator_type": "author", "first_name": "Hiromasa", "last_name": "Ogawa", "name": null }, { "creator_type": "author", "first_name": "Akira", "last_name": "Koarai", "name": null }, { "creator_type": "author", "first_name": "Tomomi", "last_name": "Kitamuro", "name": null }, { "creator_type": "author", "first_name": "Yuichi", "last_name": "Komaki", "name": null }, { "creator_type": "author", "first_name": "Takefumi", "last_name": "Akita", "name": null }, { "creator_type": "author", "first_name": "Hirohito", "last_name": "Nishino", "name": null }, { "creator_type": "author", "first_name": "Shinichiro", "last_name": "Okamoto", "name": null }, { "creator_type": "author", "first_name": "Takaaki", "last_name": "Akaike", "name": null }, { "creator_type": "author", "first_name": "Toshio", "last_name": "Hattori", "name": null } ], "identifiers": { "doi": { "normalized": "10.1080/10715760310001633817" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "15061653" } }, "mesh": [ { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Asthma", "descriptor_ui": "D001249", "major_topic": false }, { "descriptor": "Case-Control Studies", "descriptor_ui": "D016022", "major_topic": false }, { "descriptor": "Chromatography, High Pressure Liquid", "descriptor_ui": "D002851", "major_topic": false }, { "descriptor": "Electrochemistry", "descriptor_ui": "D004563", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Forced Expiratory Volume", "descriptor_ui": "D005541", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Middle Aged", "descriptor_ui": "D008875", "major_topic": false }, { "descriptor": "Nitric Oxide", "descriptor_ui": "D009569", "major_topic": false }, { "descriptor": "Proteins", "descriptor_ui": "D011506", "major_topic": false }, { "descriptor": "Pulmonary Disease, Chronic Obstructive", "descriptor_ui": "D029424", "major_topic": false }, { "descriptor": "Reference Values", "descriptor_ui": "D012016", "major_topic": false }, { "descriptor": "Sensitivity and Specificity", "descriptor_ui": "D012680", "major_topic": false }, { "descriptor": "Sputum", "descriptor_ui": "D013183", "major_topic": false }, { "descriptor": "Tyrosine", "descriptor_ui": "D014443", "major_topic": false } ], "publication": { "conference_name": null, "date": "2004 Jan", "date_precision": "unknown", "issue": "1", "normalized_date": null, "pages": "49-57", "proceedings_title": null, "publisher": "", "title": "Free radical research", "volume": "38", "year": 2004 }, "ssbd": { "database": [], "repository": [] }, "title": "Quantitative assessment of protein-bound tyrosine nitration in airway secretions from patients with inflammatory airway disease.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "During lamination of the cerebellar cortex, granule cells initially migrate tangentially along the external granule layer, and then make a vertical turn and migrate radially to the internal granule layer. We comparatively analyzed the properties of biphasic migration of granule cells in a microexplant culture in which quantitation of morphology and subcellular localization of molecules were readily accomplished. Tangential migration was guided by a leading process that later formed a parallel fiber axon. Translocation of the soma within the axonal process occurred independently of the rapid displacement of the large growth cone. On the other hand, radial migration was guided by a leading process that differentiated into a dendrite after completion of migration. Displacement of the soma and the tiny growth cone were linked so that the radial leading process adopted locomotion and kept a constant length. We propose that the dual phases of granule cell migration are achieved by distinct cellular mechanisms guided by the leading processes forming an axon and a dendrite, respectively.", "classifications": [ { "id": "Eiraku", "label": "Group Eiraku", "parent": "Eiraku", "type": "group" }, { "id": "Eiraku", "label": "Team Eiraku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Kousuke", "last_name": "Kawaji", "name": null }, { "creator_type": "author", "first_name": "Hiroki", "last_name": "Umeshima", "name": null }, { "creator_type": "author", "first_name": "Mototsugu", "last_name": "Eiraku", "name": null }, { "creator_type": "author", "first_name": "Tomoo", "last_name": "Hirano", "name": null }, { "creator_type": "author", "first_name": "Mineko", "last_name": "Kengaku", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/j.mcn.2003.10.006" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "15019940" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Animals, Newborn", "descriptor_ui": "D000831", "major_topic": false }, { "descriptor": "Cell Communication", "descriptor_ui": "D002450", "major_topic": false }, { "descriptor": "Cell Differentiation", "descriptor_ui": "D002454", "major_topic": false }, { "descriptor": "Cell Movement", "descriptor_ui": "D002465", "major_topic": false }, { "descriptor": "Cell Polarity", "descriptor_ui": "D016764", "major_topic": false }, { "descriptor": "Cell Size", "descriptor_ui": "D048429", "major_topic": false }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Cerebellar Cortex", "descriptor_ui": "D002525", "major_topic": false }, { "descriptor": "Cues", "descriptor_ui": "D003463", "major_topic": false }, { "descriptor": "Dendrites", "descriptor_ui": "D003712", "major_topic": false }, { "descriptor": "Growth Cones", "descriptor_ui": "D020439", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false } ], "publication": { "conference_name": null, "date": "2004 Feb", "date_precision": "unknown", "issue": "2", "normalized_date": null, "pages": "228-240", "proceedings_title": null, "publisher": "", "title": "Molecular and cellular neurosciences", "volume": "25", "year": 2004 }, "ssbd": { "database": [], "repository": [] }, "title": "Dual phases of migration of cerebellar granule cells guided by axonal and dendritic leading processes.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Spatiotemporal control of the Ras/ERK MAP kinase signaling pathway is a key factor for determining the specificity of cellular responses including cell proliferation, cell differentiation and cell survival. The fidelity of this signaling is regulated by docking interactions as well as scaffolding. Subcellular localization of ERK is controlled by cytoplasmic ERK anchoring proteins that have a nuclear export signal (NES), such as MEK. In quiescent cells, ERK and MEK localize to the cytoplasm. In response to stimulation, dissociation of the MEK-ERK complex is induced and activated ERK translocates to the nucleus. Recently, several negative regulators for Ras/ERK signaling have been identified and their detailed molecular mechanisms have been analyzed. Among them, Sprouty and Sef act as a temporal and a spatial regulator, respectively, for Ras/ERK signaling. Thus, multiple factors are involved in control of Ras/ERK signaling.", "classifications": [ { "id": "Yamamoto", "label": "Group Yamamoto", "parent": "Toyoshima", "type": "group" }, { "id": "Toyoshima", "label": "Team Toyoshima", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Satoru", "last_name": "Torii", "name": null }, { "creator_type": "author", "first_name": "Kei", "last_name": "Nakayama", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Eisuke", "last_name": "Nishida", "name": null } ], "identifiers": { "doi": { "normalized": "10.1093/jb/mvh159" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "15632293" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Extracellular Signal-Regulated MAP Kinases", "descriptor_ui": "D048049", "major_topic": false }, { "descriptor": "MAP Kinase Signaling System", "descriptor_ui": "D020935", "major_topic": false }, { "descriptor": "Membrane Proteins", "descriptor_ui": "D008565", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false } ], "publication": { "conference_name": null, "date": "2004 Nov", "date_precision": "unknown", "issue": "5", "normalized_date": null, "pages": "557-561", "proceedings_title": null, "publisher": "", "title": "Journal of biochemistry", "volume": "136", "year": 2004 }, "ssbd": { "database": [], "repository": [] }, "title": "Regulatory mechanisms and function of ERK MAP kinases.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Estrogen has been postulated to be involved in inhibition of vascular smooth muscle cell (VSMC) proliferation mainly via estrogen receptor (ER), but the detailed mechanism has remained primarily unknown. Therefore, in this study, microarray analysis was used in two types of cultured human VSMCs: one positive for ER alpha, and the other for ER beta, which were treated by estrogens to detect the estrogen-responsive genes. We also used quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) to evaluate mRNA levels of selective target gene (TG) in these cells. We further studied whether the TG product was involved in inhibition of proliferation using small interfering RNA (siRNA) of the TG transfection. We subsequently used quantitative RT-PCR and in situ hybridization analysis to evaluate the expression of these gene products in human aorta. E4F1, a possible inducer of cell growth arrest, was markedly increased only in ER alpha-positive VSMCs by estrogens in both microarray and RT-PCR analyses. Blocking of E4F1 using siRNA suppressed estrogenic inhibition of ER alpha-positive VSMC proliferation. E4F1 mRNA was abundant in premenopausal female aorta with mild atherosclerotic changes. E4F1 is therefore considered one of the estrogen-responsive genes involving ER alpha-mediated inhibition of VSMC proliferation and may play an important role in estrogen-related atheroprotection of human aorta.", "classifications": [ { "id": "Suzuki", "label": "Group Suzuki", "parent": "Takekawa", "type": "group" }, { "id": "Takekawa", "label": "Team Takekawa", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yasuhiro", "last_name": "Nakamura", "name": null }, { "creator_type": "author", "first_name": "Katsuhide", "last_name": "Igarashi", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Jun", "last_name": "Kanno", "name": null }, { "creator_type": "author", "first_name": "Tohru", "last_name": "Inoue", "name": null }, { "creator_type": "author", "first_name": "Chika", "last_name": "Tazawa", "name": null }, { "creator_type": "author", "first_name": "Masayuki", "last_name": "Saruta", "name": null }, { "creator_type": "author", "first_name": "Tomoko", "last_name": "Ando", "name": null }, { "creator_type": "author", "first_name": "Noriko", "last_name": "Moriyama", "name": null }, { "creator_type": "author", "first_name": "Toru", "last_name": "Furukawa", "name": null }, { "creator_type": "author", "first_name": "Masao", "last_name": "Ono", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Moriya", "name": null }, { "creator_type": "author", "first_name": "Kiyoshi", "last_name": "Ito", "name": null }, { "creator_type": "author", "first_name": "Haruo", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Tadashi", "last_name": "Ishibashi", "name": null }, { "creator_type": "author", "first_name": "Shoki", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Shogo", "last_name": "Yamada", "name": null }, { "creator_type": "author", "first_name": "Hironobu", "last_name": "Sasano", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/s0002-9440(10)63253-1" }, "pmcid": { "normalized": "PMC1618705" }, "pmid": { "normalized": "15579445" } }, "mesh": [ { "descriptor": "Adenovirus E4 Proteins", "descriptor_ui": "D017504", "major_topic": false }, { "descriptor": "Aorta", "descriptor_ui": "D001011", "major_topic": false }, { "descriptor": "Arteriosclerosis", "descriptor_ui": "D001161", "major_topic": false }, { "descriptor": "Cell Proliferation", "descriptor_ui": "D049109", "major_topic": false }, { "descriptor": "Estrogen Receptor alpha", "descriptor_ui": "D047628", "major_topic": false }, { "descriptor": "Estrogen Receptor beta", "descriptor_ui": "D047629", "major_topic": false }, { "descriptor": "Estrogens", "descriptor_ui": "D004967", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Gene Expression Profiling", "descriptor_ui": "D020869", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Microarray Analysis", "descriptor_ui": "D046228", "major_topic": false }, { "descriptor": "Muscle, Smooth, Vascular", "descriptor_ui": "D009131", "major_topic": false }, { "descriptor": "Oligonucleotide Array Sequence Analysis", "descriptor_ui": "D020411", "major_topic": false }, { "descriptor": "Phosphoproteins", "descriptor_ui": "D010750", "major_topic": false }, { "descriptor": "Premenopause", "descriptor_ui": "D017697", "major_topic": false }, { "descriptor": "Repressor Proteins", "descriptor_ui": "D012097", "major_topic": false }, { "descriptor": "Reverse Transcriptase Polymerase Chain Reaction", "descriptor_ui": "D020133", "major_topic": false }, { "descriptor": "RNA, Messenger", "descriptor_ui": "D012333", "major_topic": false }, { "descriptor": "RNA, Small Interfering", "descriptor_ui": "D034741", "major_topic": false } ], "publication": { "conference_name": null, "date": "2004 Dec", "date_precision": "unknown", "issue": "6", "normalized_date": null, "pages": "2019-2031", "proceedings_title": null, "publisher": "", "title": "The American journal of pathology", "volume": "165", "year": 2004 }, "ssbd": { "database": [], "repository": [] }, "title": "E4F1, a novel estrogen-responsive gene in possible atheroprotection, revealed by microarray analysis.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Heparanase is an endo-beta-D-glucuronidase that degrades heparan sulfate glycosaminoglycans in the extracellular matrix and the basement membrane and is well known to be involved in tumor cell invasion and angiogenesis. We have focused on heparanase as a target for antitumor agents, especially antimetastatic agents. (R)-3-hexadecanoyl-5-hydroxymethyltetronic acid (RK-682) was found to display an inhibitory activity against heparanase in our screening of natural sources. Because RK-682 has been reported to show inhibitory activities against several enzymes, we have tried to develop selective heparanase inhibitors using the method of rational drug design. Based on the structure of the heparanase/RK-682 complex, we speculated that selective inhibitory activity against heparanase could be acquired by arylalkylation, namely, by benzylation of the 4-position of RK-682. Among the rationally designed 4-alkyl-RK-682 derivatives, 4-benzyl-RK-682 has been found to possess a selective inhibitory activity for heparanase (IC50 for heparanase, 17 micromol/L; IC50 for other enzymes, >100 micromol/L). 4-Benzyl-RK-682 also inhibited the invasion and migration of human fibrosarcoma HT1080 cells (IC50 for invasion, 1.5 micromol/L; IC50 for migration, 3.0 micromol/L). On the other hand, RK-682 had no inhibitory effect on the invasion and migration of HT1080 cells at doses of up to 100 micromol/L.", "classifications": [ { "id": "Sodeoka", "label": "Group Sodeoka", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Keisuke", "last_name": "Ishida", "name": null }, { "creator_type": "author", "first_name": "Go", "last_name": "Hirai", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Murakami", "name": null }, { "creator_type": "author", "first_name": "Takayuki", "last_name": "Teruya", "name": null }, { "creator_type": "author", "first_name": "Siro", "last_name": "Simizu", "name": null }, { "creator_type": "author", "first_name": "Mikiko", "last_name": "Sodeoka", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Osada", "name": null } ], "identifiers": { "doi": { "normalized": null }, "pmcid": { "normalized": null }, "pmid": { "normalized": "15367701" } }, "mesh": [ { "descriptor": "Antineoplastic Agents", "descriptor_ui": "D000970", "major_topic": false }, { "descriptor": "Cell Movement", "descriptor_ui": "D002465", "major_topic": false }, { "descriptor": "Drug Design", "descriptor_ui": "D015195", "major_topic": false }, { "descriptor": "Glucuronidase", "descriptor_ui": "D005966", "major_topic": false }, { "descriptor": "Heparanase", "descriptor_ui": "D000099175", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Ligands", "descriptor_ui": "D008024", "major_topic": false }, { "descriptor": "Neoplasm Invasiveness", "descriptor_ui": "D009361", "major_topic": false }, { "descriptor": "Neoplasm Metastasis", "descriptor_ui": "D009362", "major_topic": true }, { "descriptor": "Phosphoprotein Phosphatases", "descriptor_ui": "D010749", "major_topic": false }, { "descriptor": "Structure-Activity Relationship", "descriptor_ui": "D013329", "major_topic": false } ], "publication": { "conference_name": null, "date": "2004 Sep", "date_precision": "unknown", "issue": "9", "normalized_date": null, "pages": "1069-1077", "proceedings_title": null, "publisher": "", "title": "Molecular cancer therapeutics", "volume": "3", "year": 2004 }, "ssbd": { "database": [], "repository": [] }, "title": "Structure-based design of a selective heparanase inhibitor as an antimetastatic agent.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Although the supralinear summation of synchronizing excitatory postsynaptic potentials (EPSPs) and backpropagating action potentials (APs) is important for spike-timing-dependent synaptic plasticity (STDP), the spatial conditions of the amplification in the divergent dendritic structure have yet to be analyzed. In the present study, we simulated the coincidence of APs with EPSPs at randomly determined synaptic sites of a morphologically reconstructed hippocampal CA1 pyramidal model neuron and clarified the spatial condition of the amplifying synapses. In the case of uniform conductance inputs, the amplifying synapses were localized in the middle apical dendrites and distal basal dendrites with small diameters, and the ratio of synapses was unexpectedly small: 8-16% in both apical and basal dendrites. This was because the appearance of strong amplification requires the coincidence of both APs of 3-30 mV and EPSPs of over 6 mV, both of which depend on the dendritic location of synaptic sites. We found that the localization of amplifying synapses depends on A-type K+ channel distribution because backpropagating APs depend on the A-type K+ channel distribution, and that the localizations of amplifying synapses were similar within a range of physiological synaptic conductances. We also quantified the spread of membrane amplification in dendrites, indicating that the neighboring synapses can also show the amplification. These findings allowed us to computationally illustrate the spatial localization of synapses for supralinear summation of APs and EPSPs within thin dendritic branches where patch clamp experiments cannot be easily conducted.", "classifications": [ { "id": "Kuroda", "label": "Group Kuroda", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Hidetoshi", "last_name": "Urakubo", "name": null }, { "creator_type": "author", "first_name": "Takeshi", "last_name": "Aihara", "name": null }, { "creator_type": "author", "first_name": "Shinya", "last_name": "Kuroda", "name": null }, { "creator_type": "author", "first_name": "Masataka", "last_name": "Watanabe", "name": null }, { "creator_type": "author", "first_name": "Shunsuke", "last_name": "Kondo", "name": null } ], "identifiers": { "doi": { "normalized": "10.1023/b:jcns.0000025688.64836.df" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "15114049" } }, "mesh": [ { "descriptor": "Action Potentials", "descriptor_ui": "D000200", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Computer Simulation", "descriptor_ui": "D003198", "major_topic": true }, { "descriptor": "Dendrites", "descriptor_ui": "D003712", "major_topic": false }, { "descriptor": "Electric Stimulation", "descriptor_ui": "D004558", "major_topic": false }, { "descriptor": "Electrophysiology", "descriptor_ui": "D004594", "major_topic": false }, { "descriptor": "Excitatory Postsynaptic Potentials", "descriptor_ui": "D019706", "major_topic": false }, { "descriptor": "Hippocampus", "descriptor_ui": "D006624", "major_topic": false }, { "descriptor": "Membrane Potentials", "descriptor_ui": "D008564", "major_topic": false }, { "descriptor": "Models, Neurological", "descriptor_ui": "D008959", "major_topic": false }, { "descriptor": "Neural Conduction", "descriptor_ui": "D009431", "major_topic": false }, { "descriptor": "Neuronal Plasticity", "descriptor_ui": "D009473", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Potassium Channels", "descriptor_ui": "D015221", "major_topic": false }, { "descriptor": "Synapses", "descriptor_ui": "D013569", "major_topic": false }, { "descriptor": "Synaptic Transmission", "descriptor_ui": "D009435", "major_topic": false }, { "descriptor": "Time Factors", "descriptor_ui": "D013997", "major_topic": false } ], "publication": { "conference_name": null, "date": "2004 May-Jun", "date_precision": "unknown", "issue": "3", "normalized_date": null, "pages": "251-265", "proceedings_title": null, "publisher": "", "title": "Journal of computational neuroscience", "volume": "16", "year": 2004 }, "ssbd": { "database": [], "repository": [] }, "title": "Spatial localization of synapses required for supralinear summation of action potentials and EPSPs.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The risk of developing second primary cancers is increased in patients with breast cancer. The lung is one of the major target organs, and therefore a differential diagnosis between primary and metastatic cancers is required for the treatment of lung tumors in patients with a history of breast cancer. However, biopsy specimens frequently result in small, fragmented tissues containing only a few, degenerated cancer cells. We attempted to find a useful marker for differential diagnosis, using the online SAGE database. We selected three molecules, small breast epithelial mucin (SBEM), prostate epithelium-specific Ets transcription factor (PDEF), and mammaglobin (MGB1), as potential markers for breast cancer. SBEM and PDEF proved of no use for practical differential diagnosis because they are expressed in the normal bronchus. In contrast, expression of MGB1 was detected in all 22 primary breast cancers, but not in 22 normal lung tissues. Furthermore, all 12 metastatic breast cancers examined demonstrated positive MGB1 transcripts, whereas one of 48 primary lung adenocarcinomas expressed MGB1. This suggests that MGB1 can serve as a differential molecular marker. In practice, prospective examination, using the nine cases with a history of breast cancer, confirmed the usefulness of MGB1 in differential diagnosis.", "classifications": [ { "id": "Yatabe", "label": "Group Yatabe", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Takaomi", "last_name": "Koga", "name": null }, { "creator_type": "author", "first_name": "Yoshitsugu", "last_name": "Horio", "name": null }, { "creator_type": "author", "first_name": "Tetsuya", "last_name": "Mitsudomi", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Yatabe", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/s1525-1578(10)60495-3" }, "pmcid": { "normalized": "PMC1867472" }, "pmid": { "normalized": "15096563" } }, "mesh": [ { "descriptor": "Adenocarcinoma", "descriptor_ui": "D000230", "major_topic": false }, { "descriptor": "Aged", "descriptor_ui": "D000368", "major_topic": false }, { "descriptor": "Aged, 80 and over", "descriptor_ui": "D000369", "major_topic": false }, { "descriptor": "Biomarkers, Tumor", "descriptor_ui": "D014408", "major_topic": false }, { "descriptor": "Breast Neoplasms", "descriptor_ui": "D001943", "major_topic": false }, { "descriptor": "Bronchi", "descriptor_ui": "D001980", "major_topic": false }, { "descriptor": "Diagnosis, Differential", "descriptor_ui": "D003937", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Gene Expression Profiling", "descriptor_ui": "D020869", "major_topic": false }, { "descriptor": "Gene Expression Regulation, Neoplastic", "descriptor_ui": "D015972", "major_topic": true }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Lung", "descriptor_ui": "D008168", "major_topic": false }, { "descriptor": "Lung Neoplasms", "descriptor_ui": "D008175", "major_topic": false }, { "descriptor": "Lymphatic Metastasis", "descriptor_ui": "D008207", "major_topic": false }, { "descriptor": "Mammaglobin A", "descriptor_ui": "D060785", "major_topic": false }, { "descriptor": "Mucins", "descriptor_ui": "D009077", "major_topic": false }, { "descriptor": "Neoplasm Proteins", "descriptor_ui": "D009363", "major_topic": false }, { "descriptor": "Prospective Studies", "descriptor_ui": "D011446", "major_topic": false }, { "descriptor": "Proto-Oncogene Proteins c-ets", "descriptor_ui": "D050783", "major_topic": false }, { "descriptor": "Transcription Factors", "descriptor_ui": "D014157", "major_topic": false }, { "descriptor": "Uteroglobin", "descriptor_ui": "D014598", "major_topic": false } ], "publication": { "conference_name": null, "date": "2004 May", "date_precision": "unknown", "issue": "2", "normalized_date": null, "pages": "90-95", "proceedings_title": null, "publisher": "", "title": "The Journal of molecular diagnostics : JMD", "volume": "6", "year": 2004 }, "ssbd": { "database": [], "repository": [] }, "title": "Identification of MGB1 as a marker in the differential diagnosis of lung tumors in patients with a history of breast cancer by analysis of publicly available SAGE data.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The study of the metabolomics of primary metabolites using conventional chemical analyses requires a high-throughput method. Chemical derivatizations are a prerequisite for gas-chromatographic separation, and a large sample quantity is needed for liquid-chromatographic separation and nuclear magnetic resonance detection systems. Recently, we have developed a capillary electrophoresis-mass spectrometry (CE-MS) technology that can simultaneously quantify a large number of primary metabolites, using only a small quantity of samples, and without any chemical derivatizations. Parallel use of a capillary electrophoresis-diode array detector (CE-DAD) system further enables almost all water-soluble intracellular metabolites to be analyzed. We demonstrate, with rice leaves, a simple and rapid method of sample preparation for CE analysis; using this method, we have successfully measured the levels of 88 main metabolites involved in glycolysis, the tricarboxylic acid cycle, the pentose phosphate pathway, photorespiration, and amino acid biosynthesis.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Shigeru", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Takaaki", "last_name": "Nishioka", "name": null }, { "creator_type": "author", "first_name": "Masaru", "last_name": "Tomita", "name": null } ], "identifiers": { "doi": { "normalized": "10.1111/j.1365-313x.2004.02187.x" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "15361149" } }, "mesh": [ { "descriptor": "Electrophoresis, Capillary", "descriptor_ui": "D019075", "major_topic": false }, { "descriptor": "Glutamic Acid", "descriptor_ui": "D018698", "major_topic": false }, { "descriptor": "Mass Spectrometry", "descriptor_ui": "D013058", "major_topic": false }, { "descriptor": "Monosaccharides", "descriptor_ui": "D009005", "major_topic": false }, { "descriptor": "Oryza", "descriptor_ui": "D012275", "major_topic": false }, { "descriptor": "Plant Leaves", "descriptor_ui": "D018515", "major_topic": false }, { "descriptor": "Ribonucleotides", "descriptor_ui": "D012265", "major_topic": false } ], "publication": { "conference_name": null, "date": "2004 Oct", "date_precision": "unknown", "issue": "1", "normalized_date": null, "pages": "151-163", "proceedings_title": null, "publisher": "", "title": "The Plant journal : for cell and molecular biology", "volume": "40", "year": 2004 }, "ssbd": { "database": [], "repository": [] }, "title": "Simultaneous determination of the main metabolites in rice leaves using capillary electrophoresis mass spectrometry and capillary electrophoresis diode array detection.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "We describe a method to identify and quantify amino acids using capillary electrophoresis-electrospray ionization-triple-quadrupole tandem mass spectrometry (CE-ESI-MS/MS). Amino acids, including physiological amino acids, were first separated by CE under acidic pH conditions and then detected by MS/MS. To efficiently introduce the whole sample into the capillary, no electrical potential was applied to the electrospray probe until running electrophoresis. The position of the electrosprayer with respect to the MS capillary entrance drastically affected sensitivity and generation of cluster ions. MS/MS with multiple reaction monitoring (MRM) detection was performed to obtain sufficient selectivity and sensitivity. Under optimized CE-MS/MS conditions, the minimum detectable levels for 32 free amino acids normally found in proteins and other physiological amino acids were between 0.1 and 14 micromol/L with pressure injection of 50 mbar for 3 s (3 nL) at a signal-to-noise ratio of 3. For most amino acids, this constitutes a severalfold increase in sensitivity compared to CE-MS. The relative standard deviations (% RSD) for all amino acids were better than 0.4% for migration times and between 1.4% and 8.6% for peak areas (n = 10). Since amino acids exhibited characteristic MS/MS spectra, this approach is useful for the simultaneous, selective, quantitative, and reproducible analysis of amino acids in physiological and biological samples that contain various kinds of matrices. The power of the method was demonstrated by analyzing amino acids in human urine.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Yuji", "last_name": "Kakazu", "name": null }, { "creator_type": "author", "first_name": "Martin", "last_name": "Robert", "name": null }, { "creator_type": "author", "first_name": "Masaru", "last_name": "Tomita", "name": null }, { "creator_type": "author", "first_name": "Takaaki", "last_name": "Nishioka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1002/elps.200305791" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "15237395" } }, "mesh": [ { "descriptor": "Amino Acids", "descriptor_ui": "D000596", "major_topic": false }, { "descriptor": "Electrophoresis, Capillary", "descriptor_ui": "D019075", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Reproducibility of Results", "descriptor_ui": "D015203", "major_topic": false }, { "descriptor": "Sensitivity and Specificity", "descriptor_ui": "D012680", "major_topic": false }, { "descriptor": "Spectrometry, Mass, Electrospray Ionization", "descriptor_ui": "D021241", "major_topic": false }, { "descriptor": "Time Factors", "descriptor_ui": "D013997", "major_topic": false } ], "publication": { "conference_name": null, "date": "2004 Jul", "date_precision": "unknown", "issue": "13", "normalized_date": null, "pages": "1964-1972", "proceedings_title": null, "publisher": "", "title": "Electrophoresis", "volume": "25", "year": 2004 }, "ssbd": { "database": [], "repository": [] }, "title": "Qualitative and quantitative analysis of amino acids by capillary electrophoresis-electrospray ionization-tandem mass spectrometry.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Mdm2 oncoprotein plays a major role in inhibiting the p53 tumor suppressor protein. Here, we investigate phosphorylation of Mdm2 at serine 407 (S407). S407 is phosphorylated in cells after treatment with camptothecin (CPT) or hydroxyurea, inhibitors of DNA replication. S407 phosphorylation after CPT treatment is induced upon cell cycle arrest during S phase and prevented if entry into S phase of cell cycle is blocked. We found that a major kinase responsible for S407 phosphorylation is ATR, a DNA damage checkpoint protein that induces cell cycle arrest and promotes DNA repair in response to impaired DNA replication; induction of S407 phosphorylation is enhanced after expression of wild-type ATR, while it is inhibited by a dominant-negative form of ATR. Further, S407 is specifically phosphorylated by ATR in vitro. Substitution of S407 with aspartate (S407D), but not with alanine (S407A), promotes nuclear localization of p53. Taken together, our data indicate that S407 phosphorylation of Mdm2 by ATR reduces Mdm2-dependent export of p53 from nuclei to cytoplasm.", "classifications": [ { "id": "Okamoto", "label": "Group Okamoto", "parent": "Okamoto", "type": "group" }, { "id": "Okamoto", "label": "Team Okamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Tomomi", "last_name": "Shinozaki", "name": null }, { "creator_type": "author", "first_name": "Ayumi", "last_name": "Nota", "name": null }, { "creator_type": "author", "first_name": "Yoichi", "last_name": "Taya", "name": null }, { "creator_type": "author", "first_name": "Koji", "last_name": "Okamoto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/sj.onc.1207176" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "14654783" } }, "mesh": [ { "descriptor": "Amino Acid Sequence", "descriptor_ui": "D000595", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Aspartic Acid", "descriptor_ui": "D001224", "major_topic": false }, { "descriptor": "Ataxia Telangiectasia Mutated Proteins", "descriptor_ui": "D064007", "major_topic": false }, { "descriptor": "Cell Cycle", "descriptor_ui": "D002453", "major_topic": false }, { "descriptor": "Cell Cycle Proteins", "descriptor_ui": "D018797", "major_topic": true }, { "descriptor": "Cell Nucleus", "descriptor_ui": "D002467", "major_topic": false }, { "descriptor": "DNA Damage", "descriptor_ui": "D004249", "major_topic": false }, { "descriptor": "Down-Regulation", "descriptor_ui": "D015536", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Molecular Sequence Data", "descriptor_ui": "D008969", "major_topic": false }, { "descriptor": "Nuclear Proteins", "descriptor_ui": "D009687", "major_topic": true }, { "descriptor": "Phosphorylation", "descriptor_ui": "D010766", "major_topic": false }, { "descriptor": "Protein Serine-Threonine Kinases", "descriptor_ui": "D017346", "major_topic": false }, { "descriptor": "Proto-Oncogene Proteins", "descriptor_ui": "D011518", "major_topic": false }, { "descriptor": "Proto-Oncogene Proteins c-mdm2", "descriptor_ui": "D051736", "major_topic": false }, { "descriptor": "S Phase", "descriptor_ui": "D016196", "major_topic": false }, { "descriptor": "Serine", "descriptor_ui": "D012694", "major_topic": false }, { "descriptor": "Tumor Suppressor Protein p53", "descriptor_ui": "D016159", "major_topic": false } ], "publication": { "conference_name": null, "date": "2003 Dec 4", "date_precision": "day", "issue": "55", "normalized_date": "2003-12-04", "pages": "8870-8880", "proceedings_title": null, "publisher": "", "title": "Oncogene", "volume": "22", "year": 2003 }, "ssbd": { "database": [], "repository": [] }, "title": "Functional role of Mdm2 phosphorylation by ATR in attenuation of p53 nuclear export.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "NF-κB downregulates tumor necrosis factor (TNF)-induced c-Jun N-terminal kinase (JNK) activation that promotes cell death, but the mechanism is not yet fully understood. By using murine embryonic fibroblasts (MEFs) that are deficient in TNF receptor-associated factor (TRAF) 2 and TRAF5 (DKO) or p65 NF-κB subunit (p65KO), we demonstrate here that TNF stimulation leads to accumulation of reactive oxygen species (ROS), which is essential for prolonged mitogen-activated protein kinase (MAPK) activation and cell death. Interestingly, dying cells show necrotic as well as apoptotic morphological changes as assessed by electron microscopy and flow cytometry, and necrotic, but not apoptotic, cell death is substantially inhibited by antioxidant. Importantly, TNF does not induce ROS accumulation or prolonged MAPK activation in wild-type MEFs, indicating that TRAF-mediated NF-κB activation normally suppresses the TNF-induced ROS accumulation that subsequently induces prolonged MAPK activation and necrotic cell death", "classifications": [ { "id": "Takekawa", "label": "Group Takekawa", "parent": "Takekawa", "type": "group" }, { "id": "Takekawa", "label": "Team Takekawa", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Sachiko", "last_name": "Sakon", "name": null }, { "creator_type": "author", "first_name": "Xin", "last_name": "Xue", "name": null }, { "creator_type": "author", "first_name": "Mutsuhiro", "last_name": "Takekawa", "name": null }, { "creator_type": "author", "first_name": "Tomonari", "last_name": "Sasazuki", "name": null }, { "creator_type": "author", "first_name": "Tatsuma", "last_name": "Okazaki", "name": null }, { "creator_type": "author", "first_name": "Yuko", "last_name": "Kojima", "name": null }, { "creator_type": "author", "first_name": "Jian-Hu", "last_name": "Piao", "name": null }, { "creator_type": "author", "first_name": "Hideo", "last_name": "Yagita", "name": null }, { "creator_type": "author", "first_name": "Ko", "last_name": "Okumura", "name": null }, { "creator_type": "author", "first_name": "Takahiro", "last_name": "Doi", "name": null }, { "creator_type": "author", "first_name": "Hiroyasu", "last_name": "Nakano", "name": null } ], "identifiers": { "doi": { "normalized": "10.1093/emboj/cdg379" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "12881424" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Cell Death", "descriptor_ui": "D016923", "major_topic": true }, { "descriptor": "Glutathione", "descriptor_ui": "D005978", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Microscopy, Electron", "descriptor_ui": "D008854", "major_topic": false }, { "descriptor": "Mitogen-Activated Protein Kinases", "descriptor_ui": "D020928", "major_topic": false }, { "descriptor": "NADP", "descriptor_ui": "D009249", "major_topic": false }, { "descriptor": "NF-kappa B", "descriptor_ui": "D016328", "major_topic": false }, { "descriptor": "Reactive Oxygen Species", "descriptor_ui": "D017382", "major_topic": true }, { "descriptor": "Tumor Necrosis Factor-alpha", "descriptor_ui": "D014409", "major_topic": false } ], "publication": { "conference_name": null, "date": "2003 Aug 1", "date_precision": "day", "issue": "15", "normalized_date": "2003-08-01", "pages": "3898-3909", "proceedings_title": null, "publisher": "", "title": "The EMBO Journal", "volume": "22", "year": 2003 }, "ssbd": { "database": [], "repository": [] }, "title": "NF-κB inhibits TNF-induced accumulation of ROS that mediate prolonged MAPK activation and necrotic cell death.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Mitogen-activated protein kinase (MAPK) cascades are conserved signaling modules composed of three sequentially activated kinases (MAPKKK, MAPKK and MAPK). Because individual cells contain multiple MAPK cascades, mechanisms are required to ensure the fidelity of signal transmission. In yeast, external high osmolarity activates the HOG (high osmolarity glycerol) MAPK pathway, which consists of two upstream branches (SHO1 and SLN1) and common downstream elements including the Pbs2 MAPKK and the Hog1 MAPK. The Ssk2/Ssk22 MAPKKKs in the SLN1 branch, when activated, exclusively phosphorylate the Pbs2 MAPKK. We found that this was due to an Ssk2/Ssk22-specific docking site in the Pbs2 N-terminal region. The Pbs2 docking site constitutively bound the Ssk2/Ssk22 kinase domain. Docking site mutations drastically reduced the Pbs2–Ssk2/Ssk22 interaction and hampered Hog1 activation by the SLN1 branch. Fusion of the Pbs2 docking site to a different MAPKK, Ste7, allowed phosphorylation of Ste7 by Ssk2/Ssk22. Thus, the docking site contributes to both the efficiency and specificity of signaling. During these analyses, we also found a nuclear export signal and a possible nuclear localization signal in Pbs2.", "classifications": [ { "id": "Takekawa", "label": "Group Takekawa", "parent": "Takekawa", "type": "group" }, { "id": "Takekawa", "label": "Team Takekawa", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Kazuo", "last_name": "Tatebayashi", "name": null }, { "creator_type": "author", "first_name": "Mutsuhiro", "last_name": "Takekawa", "name": null }, { "creator_type": "author", "first_name": "Haruo", "last_name": "Saito", "name": null } ], "identifiers": { "doi": { "normalized": "10.1093/emboj/cdg353" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "12853477" } }, "mesh": [ { "descriptor": "Amino Acid Sequence", "descriptor_ui": "D000595", "major_topic": false }, { "descriptor": "Cell Nucleus", "descriptor_ui": "D002467", "major_topic": false }, { "descriptor": "Enzyme Activation", "descriptor_ui": "D004789", "major_topic": false }, { "descriptor": "Fungal Proteins", "descriptor_ui": "D005656", "major_topic": false }, { "descriptor": "Intracellular Signaling Peptides and Proteins", "descriptor_ui": "D047908", "major_topic": false }, { "descriptor": "MAP Kinase Kinase Kinases", "descriptor_ui": "D020930", "major_topic": false }, { "descriptor": "MAP Kinase Signaling System", "descriptor_ui": "D020935", "major_topic": false }, { "descriptor": "Membrane Proteins", "descriptor_ui": "D008565", "major_topic": false }, { "descriptor": "Mitogen-Activated Protein Kinase Kinases", "descriptor_ui": "D020929", "major_topic": false }, { "descriptor": "Mitogen-Activated Protein Kinases", "descriptor_ui": "D020928", "major_topic": false }, { "descriptor": "Models, Biological", "descriptor_ui": "D008954", "major_topic": false }, { "descriptor": "Molecular Sequence Data", "descriptor_ui": "D008969", "major_topic": false }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": false }, { "descriptor": "Osmotic Pressure", "descriptor_ui": "D009997", "major_topic": false }, { "descriptor": "Protein Binding", "descriptor_ui": "D011485", "major_topic": false }, { "descriptor": "Protein Kinases", "descriptor_ui": "D011494", "major_topic": false }, { "descriptor": "Protein Serine-Threonine Kinases", "descriptor_ui": "D017346", "major_topic": false }, { "descriptor": "Protein Structure, Tertiary", "descriptor_ui": "D017434", "major_topic": false }, { "descriptor": "Recombinant Fusion Proteins", "descriptor_ui": "D011993", "major_topic": false }, { "descriptor": "Saccharomyces cerevisiae", "descriptor_ui": "D012441", "major_topic": false }, { "descriptor": "Saccharomyces cerevisiae Proteins", "descriptor_ui": "D029701", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false } ], "publication": { "conference_name": null, "date": "2003 Jul 15", "date_precision": "day", "issue": "14", "normalized_date": "2003-07-15", "pages": "3624-3634", "proceedings_title": null, "publisher": "", "title": "The EMBO Journal", "volume": "22", "year": 2003 }, "ssbd": { "database": [], "repository": [] }, "title": "A docking site determining specificity of Pbs2 MAPKK for Ssk2/Ssk22 MAPKKKs in the yeast HOG pathway.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "We have developed a on-chip single-cell microcultivation assay as a means of observing the adaptation process of single bacterial cells during nutrient concentration changes. This assay enables the direct observation of single cells captured in microchambers made on thin glass slides and having semipermeable membrane lids, in which cells were kept isolated with optical tweezers. After changing a medium of 0.2% (w/v) glucose concentration to make it nutrient-free 0.9% NaCl medium, the growth of all cells inserted into the medium stopped within 20 min, irrespective of their cell cycles. When a nutrient-rich medium was restored, the cells started to grow again, even after the medium had remained nutrient-free for 42 h. The results indicate that the cell's growth and division are directly related to their nutrient condition. The growth curve also indicates that the cells keep their memory of what their growth and division had been before they stopped growing.", "classifications": [ { "id": "Wakamoto", "label": "Group Wakamoto", "parent": "Wakamoto", "type": "group" }, { "id": "Wakamoto", "label": "Team Wakamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Senkei", "last_name": "Umehara", "name": null }, { "creator_type": "author", "first_name": "Yuichi", "last_name": "Wakamoto", "name": null }, { "creator_type": "author", "first_name": "Ippei", "last_name": "Inoue", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Yasuda", "name": null } ], "identifiers": { "doi": { "normalized": "10.1016/s0006-291x(03)00794-0" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "12763026" } }, "mesh": [ { "descriptor": "Adaptation, Physiological", "descriptor_ui": "D000222", "major_topic": false }, { "descriptor": "Bacteriological Techniques", "descriptor_ui": "D001431", "major_topic": false }, { "descriptor": "Cell Division", "descriptor_ui": "D002455", "major_topic": false }, { "descriptor": "Culture Media", "descriptor_ui": "D003470", "major_topic": false }, { "descriptor": "Environment", "descriptor_ui": "D004777", "major_topic": false }, { "descriptor": "Escherichia coli", "descriptor_ui": "D004926", "major_topic": false }, { "descriptor": "Kinetics", "descriptor_ui": "D007700", "major_topic": false } ], "publication": { "conference_name": null, "date": "2003 Jun 6", "date_precision": "day", "issue": "3", "normalized_date": "2003-06-06", "pages": "534-540", "proceedings_title": null, "publisher": "", "title": "Biochemical and biophysical research communications", "volume": "305", "year": 2003 }, "ssbd": { "database": [], "repository": [] }, "title": "On-chip single-cell microcultivation assay for monitoring environmental effects on isolated cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "It is essential to analyze molecular basis of synaptic plasticity systematically for understanding our psychological processes and psychological disorders. Recent progress identified many signaling molecules responsible for the regulation of synaptic plasticity. However, because multiple molecular signal transduction molecules and pathways are involved, the systematic relationship between synaptic plasticity and the currently known signal transduction pathways remains obscure. To address this issue, we here focused on cerebellar long-term depression (LTD), one of the well known synaptic plasticity. We took advantage of a simulation model for cerebellar LTD based on biochemical reactions, kinetics, and explored the behaviors of complex signal transduction pathways involved in cerebellar LTD.", "classifications": [ { "id": "Kuroda", "label": "Group Kuroda", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Shinya", "last_name": "Kuroda", "name": null } ], "identifiers": { "doi": { "normalized": null }, "pmcid": { "normalized": null }, "pmid": { "normalized": "12701216" } }, "mesh": [ { "descriptor": "Cerebellar Cortex", "descriptor_ui": "D002525", "major_topic": false }, { "descriptor": "Chromosome Pairing", "descriptor_ui": "D023902", "major_topic": false }, { "descriptor": "Long-Term Synaptic Depression", "descriptor_ui": "D036881", "major_topic": false }, { "descriptor": "Models, Neurological", "descriptor_ui": "D008959", "major_topic": false }, { "descriptor": "Neuronal Plasticity", "descriptor_ui": "D009473", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false } ], "publication": { "conference_name": null, "date": "2003", "date_precision": "year", "issue": "1", "normalized_date": "2003", "pages": "97-102", "proceedings_title": null, "publisher": "", "title": "Seishin shinkeigaku zasshi = Psychiatria et neurologia Japonica", "volume": "105", "year": 2003 }, "ssbd": { "database": [], "repository": [] }, "title": "[Analysis of signal transduction pathways in cerebellar long-term depression by use of kinetic simulations].", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Calcium antagonists normalize endothelial dysfunction and improve the clinical outcome in patients with hypertension. However, the mechanism underlying these beneficial effects remains to be elucidated. Here, we show that the calcium antagonist nifedipine upregulates the expression of manganese superoxide dismutase (Mn SOD), an endogenous antioxidant enzyme, in vascular smooth muscle cells (VSMC) via cellular interactions between VSMC and endothelial cells (EC). Nifedipine induced upregulation of Mn SOD activity and expression in VSMC when cocultured with EC but not when cultured individually. NG-Monomethyl-L-arginine (L-NMMA), an inhibitor of nitric oxide (NO) synthesis, inhibited the upregulation of Mn SOD expression induced by nifedipine. Additionally, N-ethyl-2-(1-ethyl-2-hydroxy-2-nitrosohydrazino) ethanamine, a NO donor, reversed this inhibition by L-NMMA, indicating that NO may be involved in the mechanism underlying the nifedipine-induced upregulation of Mn SOD in VSMC. Preincubation of VSMC with Mn SOD antisense oligodeoxyribonucleotides (ODN) blocked the suppressive effects of nifedipine on DNA synthesis in VSMC cocultured with EC, whereas sense ODN had no effect. We conclude that the calcium antagonist nifedipine induces upregulation of Mn SOD expression in VSMC via NO derived from EC. This finding may provide some insight into the mechanism underlying the beneficial effects of calcium antagonists in patients with hypertension.", "classifications": [ { "id": "Suzuki", "label": "Group Suzuki", "parent": "Takekawa", "type": "group" }, { "id": "Takekawa", "label": "Team Takekawa", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Keisuke", "last_name": "Fukuo", "name": null }, { "creator_type": "author", "first_name": "Jin", "last_name": "Yang", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Taeko", "last_name": "Kaimoto", "name": null }, { "creator_type": "author", "first_name": "Yukihiro", "last_name": "Takemura", "name": null }, { "creator_type": "author", "first_name": "Osamu", "last_name": "Yasuda", "name": null }, { "creator_type": "author", "first_name": "Toshimitsu", "last_name": "Suhara", "name": null }, { "creator_type": "author", "first_name": "Naoyuki", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Toshio", "last_name": "Ogihara", "name": null } ], "identifiers": { "doi": { "normalized": "10.1291/hypres.26.503" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "12862208" } }, "mesh": [ { "descriptor": "Blotting, Western", "descriptor_ui": "D015153", "major_topic": false }, { "descriptor": "Calcium Channel Blockers", "descriptor_ui": "D002121", "major_topic": false }, { "descriptor": "Cell Division", "descriptor_ui": "D002455", "major_topic": false }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Coculture Techniques", "descriptor_ui": "D018920", "major_topic": false }, { "descriptor": "Endothelial Cells", "descriptor_ui": "D042783", "major_topic": false }, { "descriptor": "Enzyme Inhibitors", "descriptor_ui": "D004791", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Muscle, Smooth, Vascular", "descriptor_ui": "D009131", "major_topic": false }, { "descriptor": "Nifedipine", "descriptor_ui": "D009543", "major_topic": false }, { "descriptor": "Nitric Oxide", "descriptor_ui": "D009569", "major_topic": false }, { "descriptor": "Nitric Oxide Synthase", "descriptor_ui": "D019001", "major_topic": false }, { "descriptor": "Nitric Oxide Synthase Type III", "descriptor_ui": "D052250", "major_topic": false }, { "descriptor": "Oligonucleotides, Antisense", "descriptor_ui": "D016376", "major_topic": false }, { "descriptor": "omega-N-Methylarginine", "descriptor_ui": "D019323", "major_topic": false }, { "descriptor": "Superoxide Dismutase", "descriptor_ui": "D013482", "major_topic": false }, { "descriptor": "Tubulin", "descriptor_ui": "D014404", "major_topic": false }, { "descriptor": "Up-Regulation", "descriptor_ui": "D015854", "major_topic": false } ], "publication": { "conference_name": null, "date": "2003 Jun", "date_precision": "unknown", "issue": "6", "normalized_date": null, "pages": "503-508", "proceedings_title": null, "publisher": "", "title": "Hypertension research : official journal of the Japanese Society of Hypertension", "volume": "26", "year": 2003 }, "ssbd": { "database": [], "repository": [] }, "title": "Nifedipine upregulates manganese superoxide dismutase expression in vascular smooth muscle cells via endothelial cell-dependent pathways.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The number of known mRNA transcripts in the mouse has been greatly expanded by the RIKEN Mouse Gene Encyclopedia project. Validation of their reproducible expression in a tissue is an important contribution to the study of functional genomics. In this report, we determine the expression profile of 57,931 clones on 20 mouse tissues using cDNA microarrays. Of these 57,931 clones, 22,928 clones correspond to the FANTOM2 clone set. The set represents 20,234 transcriptional units (TUs) out of 33,409 TUs in the FANTOM2 set. We identified 7206 separate clones that satisfied stringent criteria for tissue-specific expression. Gene Ontology terms were assigned for these 7206 clones, and the proportion of 'molecular function' ontology for each tissue-specific clone was examined. These data will provide insights into the function of each tissue. Tissue-specific gene expression profiles obtained using our cDNA microarrays were also compared with the data extracted from the GNF Expression Atlas based on Affymetrix microarrays. One major outcome of the RIKEN transcriptome analysis is the identification of numerous nonprotein-coding mRNAs. The expression profile was also used to obtain evidence of expression for putative noncoding RNAs. In addition, 1926 clones (70%) of 2768 clones that were categorized as \"unknown EST,\" and 1969 (58%) clones of 3388 clones that were categorized as \"unclassifiable\" were also shown to be reproducibly expressed.", "classifications": [ { "id": "Nikaido", "label": "Group Nikaido", "parent": "Fujiwara", "type": "group" }, { "id": "Fujiwara", "label": "Team Fujiwara", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Hidemasa", "last_name": "Bono", "name": null }, { "creator_type": "author", "first_name": "Ken", "last_name": "Yagi", "name": null }, { "creator_type": "author", "first_name": "Takeya", "last_name": "Kasukawa", "name": null }, { "creator_type": "author", "first_name": "Itoshi", "last_name": "Nikaido", "name": null }, { "creator_type": "author", "first_name": "Naoko", "last_name": "Tominaga", "name": null }, { "creator_type": "author", "first_name": "Rika", "last_name": "Miki", "name": null }, { "creator_type": "author", "first_name": "Yosuke", "last_name": "Mizuno", "name": null }, { "creator_type": "author", "first_name": "Yasuhiro", "last_name": "Tomaru", "name": null }, { "creator_type": "author", "first_name": "Hitoshi", "last_name": "Goto", "name": null }, { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Nitanda", "name": null }, { "creator_type": "author", "first_name": "Daisuke", "last_name": "Shimizu", "name": null }, { "creator_type": "author", "first_name": "Hirochika", "last_name": "Makino", "name": null }, { "creator_type": "author", "first_name": "Tomoyuki", "last_name": "Morita", "name": null }, { "creator_type": "author", "first_name": "Junshin", "last_name": "Fujiyama", "name": null }, { "creator_type": "author", "first_name": "Takehito", "last_name": "Sakai", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Shimoji", "name": null }, { "creator_type": "author", "first_name": "David A.", "last_name": "Hume", "name": null }, { "creator_type": "author", "first_name": "Yoshihide", "last_name": "Hayashizaki", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Okazaki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1101/gr.1075103" }, "pmcid": { "normalized": "PMC403653" }, "pmid": { "normalized": "12819129" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Classification", "descriptor_ui": "D002965", "major_topic": false }, { "descriptor": "Cloning, Molecular", "descriptor_ui": "D003001", "major_topic": false }, { "descriptor": "Databases, Genetic", "descriptor_ui": "D030541", "major_topic": true }, { "descriptor": "DNA, Complementary", "descriptor_ui": "D018076", "major_topic": false }, { "descriptor": "Expressed Sequence Tags", "descriptor_ui": "D020224", "major_topic": false }, { "descriptor": "Gene Expression Profiling", "descriptor_ui": "D020869", "major_topic": false }, { "descriptor": "Genes", "descriptor_ui": "D005796", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Oligonucleotide Array Sequence Analysis", "descriptor_ui": "D020411", "major_topic": false }, { "descriptor": "Organ Specificity", "descriptor_ui": "D009928", "major_topic": false }, { "descriptor": "Transcription, Genetic", "descriptor_ui": "D014158", "major_topic": false } ], "publication": { "conference_name": null, "date": "2003 Jun", "date_precision": "unknown", "issue": "6B", "normalized_date": null, "pages": "1318-1323", "proceedings_title": null, "publisher": "", "title": "Genome research", "volume": "13", "year": 2003 }, "ssbd": { "database": [], "repository": [] }, "title": "Systematic expression profiling of the mouse transcriptome using RIKEN cDNA microarrays.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Dietary supplementation with eicosapentaenoic acid (EPA) improves the prognosis of chronic inflammatory diseases, including atherosclerosis. The mechanism underlying these beneficial effects, however, remains to be elucidated. Here we show that EPA protects endothelial cells from anoikis through upregulation of the cellular FLICE (Fas-associating protein with death domain-like interleukin-1-converting enzyme)-inhibitory protein (cFLIP), an endogenous inhibitor of caspase-8. EPA-induced upregulation of cFLIP expression was partially suppressed by the phosphatidylinositol-3-kinase inhibitor wortmannin. Conversely, treatment with insulinlike growth factor-1 (IGF-1), an activator of phosphatidylinositol-3-kinase/Akt signaling, or infection with an adenoviral construct expressing the constitutively active Akt gene induced upregulation of cFLIP expression. In addition, pretreatment of endothelial cells with either EPA or IGF-1 protected them from anoikis, suggesting that EPA-induced protection against anoikis is partially mediated through activation of Akt. On the other hand, when endothelial cells were already detached, treatment of these cells with EPA but not with IGF-1 protected them against anoikis. Importantly, EPA restored cFLIP expression without activating Akt signaling in detached endothelial cells, whereas IGF-1 had no effect. Additionally, exogenously restored expression of cFLIP by the tetracycline-regulated adenovirus system protected endothelial cells against anoikis. Furthermore, EPA was protective against the loss of endothelium in an organ culture of rat aortas. These findings suggest that EPA protects against endothelial cell anoikis through restoration of cFLIP expression, which might contribute to the mechanism underlying the beneficial effects of EPA in patients with hypertension.", "classifications": [ { "id": "Suzuki", "label": "Group Suzuki", "parent": "Takekawa", "type": "group" }, { "id": "Takekawa", "label": "Team Takekawa", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Takashi", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Keisuke", "last_name": "Fukuo", "name": null }, { "creator_type": "author", "first_name": "Toshimitsu", "last_name": "Suhara", "name": null }, { "creator_type": "author", "first_name": "Osamu", "last_name": "Yasuda", "name": null }, { "creator_type": "author", "first_name": "Naoyuki", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Yukihiro", "last_name": "Takemura", "name": null }, { "creator_type": "author", "first_name": "Maki", "last_name": "Tsubakimoto", "name": null }, { "creator_type": "author", "first_name": "Toshio", "last_name": "Ogihara", "name": null } ], "identifiers": { "doi": { "normalized": "10.1161/01.hyp.0000084602.06114.ad" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "12874095" } }, "mesh": [ { "descriptor": "Anoikis", "descriptor_ui": "D023102", "major_topic": false }, { "descriptor": "Aorta", "descriptor_ui": "D001011", "major_topic": false }, { "descriptor": "Apoptosis", "descriptor_ui": "D017209", "major_topic": false }, { "descriptor": "Blotting, Western", "descriptor_ui": "D015153", "major_topic": false }, { "descriptor": "Carrier Proteins", "descriptor_ui": "D002352", "major_topic": false }, { "descriptor": "CASP8 and FADD-Like Apoptosis Regulating Protein", "descriptor_ui": "D053446", "major_topic": false }, { "descriptor": "Cell Survival", "descriptor_ui": "D002470", "major_topic": false }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Eicosapentaenoic Acid", "descriptor_ui": "D015118", "major_topic": false }, { "descriptor": "Endothelium, Vascular", "descriptor_ui": "D004730", "major_topic": false }, { "descriptor": "Gene Expression", "descriptor_ui": "D015870", "major_topic": false }, { "descriptor": "Genetic Vectors", "descriptor_ui": "D005822", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Insulin-Like Growth Factor I", "descriptor_ui": "D007334", "major_topic": false }, { "descriptor": "Intracellular Signaling Peptides and Proteins", "descriptor_ui": "D047908", "major_topic": true }, { "descriptor": "Organ Culture Techniques", "descriptor_ui": "D009924", "major_topic": false }, { "descriptor": "Protein Serine-Threonine Kinases", "descriptor_ui": "D017346", "major_topic": true }, { "descriptor": "Proto-Oncogene Proteins", "descriptor_ui": "D011518", "major_topic": false }, { "descriptor": "Proto-Oncogene Proteins c-akt", "descriptor_ui": "D051057", "major_topic": false }, { "descriptor": "Transfection", "descriptor_ui": "D014162", "major_topic": false } ], "publication": { "conference_name": null, "date": "2003 Sep", "date_precision": "unknown", "issue": "3", "normalized_date": null, "pages": "342-348", "proceedings_title": null, "publisher": "", "title": "Hypertension (Dallas, Tex. : 1979)", "volume": "42", "year": 2003 }, "ssbd": { "database": [], "repository": [] }, "title": "Eicosapentaenoic acid protects endothelial cells against anoikis through restoration of cFLIP.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Manual curation has long been held to be the \"gold standard\" for functional annotation of DNA sequence. Our experience with the annotation of more than 20,000 full-length cDNA sequences revealed problems with this approach, including inaccurate and inconsistent assignment of gene names, as well as many good assignments that were difficult to reproduce using only computational methods. For the FANTOM2 annotation of more than 60,000 cDNA clones, we developed a number of methods and tools to circumvent some of these problems, including an automated annotation pipeline that provides high-quality preliminary annotation for each sequence by introducing an \"uninformative filter\" that eliminates uninformative annotations, controlled vocabularies to accurately reflect both the functional assignments and the evidence supporting them, and a highly refined, Web-based manual annotation tool that allows users to view a wide array of sequence analyses and to assign gene names and putative functions using a consistent nomenclature. The ultimate utility of our approach is reflected in the low rate of reassignment of automated assignments by manual curation. Based on these results, we propose a new standard for large-scale annotation, in which the initial automated annotations are manually investigated and then computational methods are iteratively modified and improved based on the results of manual curation.", "classifications": [ { "id": "Nikaido", "label": "Group Nikaido", "parent": "Fujiwara", "type": "group" }, { "id": "Fujiwara", "label": "Team Fujiwara", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Takeya", "last_name": "Kasukawa", "name": null }, { "creator_type": "author", "first_name": "Masaaki", "last_name": "Furuno", "name": null }, { "creator_type": "author", "first_name": "Itoshi", "last_name": "Nikaido", "name": null }, { "creator_type": "author", "first_name": "Hidemasa", "last_name": "Bono", "name": null }, { "creator_type": "author", "first_name": "David A.", "last_name": "Hume", "name": null }, { "creator_type": "author", "first_name": "Carol", "last_name": "Bult", "name": null }, { "creator_type": "author", "first_name": "David P.", "last_name": "Hill", "name": null }, { "creator_type": "author", "first_name": "Richard", "last_name": "Baldarelli", "name": null }, { "creator_type": "author", "first_name": "Julian", "last_name": "Gough", "name": null }, { "creator_type": "author", "first_name": "Alexander", "last_name": "Kanapin", "name": null }, { "creator_type": "author", "first_name": "Hideo", "last_name": "Matsuda", "name": null }, { "creator_type": "author", "first_name": "Lynn M.", "last_name": "Schriml", "name": null }, { "creator_type": "author", "first_name": "Yoshihide", "last_name": "Hayashizaki", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Okazaki", "name": null }, { "creator_type": "author", "first_name": "John", "last_name": "Quackenbush", "name": null } ], "identifiers": { "doi": { "normalized": "10.1101/gr.992803" }, "pmcid": { "normalized": "PMC403710" }, "pmid": { "normalized": "12819153" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Computational Biology", "descriptor_ui": "D019295", "major_topic": false }, { "descriptor": "Contig Mapping", "descriptor_ui": "D020451", "major_topic": false }, { "descriptor": "Databases, Genetic", "descriptor_ui": "D030541", "major_topic": false }, { "descriptor": "DNA, Complementary", "descriptor_ui": "D018076", "major_topic": false }, { "descriptor": "Electronic Data Processing", "descriptor_ui": "D001330", "major_topic": false }, { "descriptor": "Genes", "descriptor_ui": "D005796", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Information Management", "descriptor_ui": "D019451", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Quality Control", "descriptor_ui": "D011786", "major_topic": false }, { "descriptor": "Reference Standards", "descriptor_ui": "D012015", "major_topic": false }, { "descriptor": "Software Design", "descriptor_ui": "D012985", "major_topic": true }, { "descriptor": "User-Computer Interface", "descriptor_ui": "D014584", "major_topic": false } ], "publication": { "conference_name": null, "date": "2003 Jun", "date_precision": "unknown", "issue": "6B", "normalized_date": null, "pages": "1542-1551", "proceedings_title": null, "publisher": "", "title": "Genome research", "volume": "13", "year": 2003 }, "ssbd": { "database": [], "repository": [] }, "title": "Development and evaluation of an automated annotation pipeline and cDNA annotation system.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Ischemic insult to the heart produces myocyte Ca2+ ([Ca2+]i) overload. However, little is known about spatiotemporal changes in [Ca2+]i within the ischemic heart in situ at the cellular level. Using real-time confocal microscopy, we successfully visualized [Ca2+]i dynamics at the border zone on the subepicardial myocardium of the heart 2 h after coronary ligations followed by loading with fluo 3/AM. Three distinct regions were identified in the acute infarcted heart. In intact regions, the myocytes showed spatially uniform Ca2+ transients synchronously to QRS complex in the electrocardiogram. The myocytes at the infarcted regions showed no fluorescence intensity (FI). At the border zones between the intact and infarcted regions, Ca2+ waves emerged sporadically and randomly, instead of Ca2+ transients, at a mean frequency of 11.5 +/- 8.5 min/cell with a propagation velocity of 151.0 +/- 35.7 microm/sec along the longitudinal axis of the individual myocytes. In addition, some myocytes within the border zone exhibited homogeneously high static FI, indicating severe Ca2+ overload. In summary, we provided the first direct evidence of abnormal [Ca2+]i dynamics in acute infarcted hearts at the cellular level. The observed diversity in spatiotemporal [Ca2+]i dynamics at the border zone may contribute to the arrhythmias or contractile failure in acute myocardial infarction.", "classifications": [ { "id": "Tanaka", "label": "Group Tanaka", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Eiji", "last_name": "Tsujii", "name": null }, { "creator_type": "author", "first_name": "Hideo", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Masahito", "last_name": "Oyamada", "name": null }, { "creator_type": "author", "first_name": "Katsumasa", "last_name": "Fujita", "name": null }, { "creator_type": "author", "first_name": "Tetsu", "last_name": "Hamamoto", "name": null }, { "creator_type": "author", "first_name": "Tetsuro", "last_name": "Takamatsu", "name": null } ], "identifiers": { "doi": { "normalized": "10.1023/a:1024188302849" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "12870665" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Calcium", "descriptor_ui": "D002118", "major_topic": false }, { "descriptor": "Electrocardiography", "descriptor_ui": "D004562", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Microscopy, Confocal", "descriptor_ui": "D018613", "major_topic": false }, { "descriptor": "Microscopy, Fluorescence", "descriptor_ui": "D008856", "major_topic": false }, { "descriptor": "Myocardial Contraction", "descriptor_ui": "D009200", "major_topic": false }, { "descriptor": "Myocardial Infarction", "descriptor_ui": "D009203", "major_topic": false }, { "descriptor": "Myocardial Ischemia", "descriptor_ui": "D017202", "major_topic": false }, { "descriptor": "Myocardium", "descriptor_ui": "D009206", "major_topic": false }, { "descriptor": "Myocytes, Cardiac", "descriptor_ui": "D032383", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Rats, Wistar", "descriptor_ui": "D017208", "major_topic": false }, { "descriptor": "Time Factors", "descriptor_ui": "D013997", "major_topic": false } ], "publication": { "conference_name": null, "date": "2003 Jun", "date_precision": "unknown", "issue": "1-2", "normalized_date": null, "pages": "135-139", "proceedings_title": null, "publisher": "", "title": "Molecular and cellular biochemistry", "volume": "248", "year": 2003 }, "ssbd": { "database": [], "repository": [] }, "title": "In situ visualization of the intracellular Ca2+ dynamics at the border of the acute myocardial infarct.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "A new approach for the comprehensive and quantitative analysis of charged metabolites by capillary electrophoresis mass spectrometry (CE-MS) is proposed. Metabolites are first separated by CE based on charge and size and then selectively detected using MS by monitoring over a large range of m/z values. This method enabled the determination of 352 metabolic standards and its utility was demonstrated in the analysis of 1692 metabolites from Bacillus subtilis extracts, revealing significant changes in metabolites during B. subtilis sporulation.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Yoshiaki", "last_name": "Ohashi", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Ueno", "name": null }, { "creator_type": "author", "first_name": "Hisako", "last_name": "Naraoka", "name": null }, { "creator_type": "author", "first_name": "Masaru", "last_name": "Tomita", "name": null }, { "creator_type": "author", "first_name": "Takaaki", "last_name": "Nishioka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/pr034020m" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "14582645" } }, "mesh": [ { "descriptor": "Anions", "descriptor_ui": "D000838", "major_topic": false }, { "descriptor": "Bacillus subtilis", "descriptor_ui": "D001412", "major_topic": false }, { "descriptor": "Bacterial Proteins", "descriptor_ui": "D001426", "major_topic": false }, { "descriptor": "Cations", "descriptor_ui": "D002412", "major_topic": false }, { "descriptor": "Coenzyme A", "descriptor_ui": "D003065", "major_topic": false }, { "descriptor": "Electrophoresis, Capillary", "descriptor_ui": "D019075", "major_topic": false }, { "descriptor": "Glycolysis", "descriptor_ui": "D006019", "major_topic": false }, { "descriptor": "Mass Spectrometry", "descriptor_ui": "D013058", "major_topic": false }, { "descriptor": "Models, Chemical", "descriptor_ui": "D008956", "major_topic": false }, { "descriptor": "Nucleotides", "descriptor_ui": "D009711", "major_topic": false }, { "descriptor": "Spores, Bacterial", "descriptor_ui": "D013171", "major_topic": false } ], "publication": { "conference_name": null, "date": "2003 Sep-Oct", "date_precision": "unknown", "issue": "5", "normalized_date": null, "pages": "488-494", "proceedings_title": null, "publisher": "", "title": "Journal of proteome research", "volume": "2", "year": 2003 }, "ssbd": { "database": [], "repository": [] }, "title": "Quantitative metabolome analysis using capillary electrophoresis mass spectrometry.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The complete set of cDNAs encoding the enzymes of known metabolic pathways has not previously been available for any mammal. Here, transcripts encoding the metabolic pathways of the mouse (mouse metabolome) were reconstructed by making use of the KEGG metabolic pathway database and gene ontology (GO) assignment to the mouse representative transcript and protein set (RTPS), which contains all available mouse transcript sequences including the FANTOM set of RIKEN mouse cDNA clones. By assigning EC numbers extracted from the molecular function ontology in GO, the known mouse transcriptome was predicted to encode enzymes with 726 unique EC numbers. Of these, 648 EC numbers were newly assigned based on the FANTOM set. The mouse metabolome confirmed by cDNA analysis includes almost all of the enzymes of well known pathways such as the tricarboxylic acid cycle and urea cycle. On the other hand, analysis of enzymes required for the tryptophan metabolism pathway revealed a lack of connectivity, indicating that cDNAs/genes encoding several key enzymes remain to be identified. The information derived from coexpression from the cDNA microarray analysis of enzymes of known function may lead to identification of the missing components of the metabolome, and will add new insights into the connectivity of the mammalian metabolic pathways.", "classifications": [ { "id": "Nikaido", "label": "Group Nikaido", "parent": "Fujiwara", "type": "group" }, { "id": "Fujiwara", "label": "Team Fujiwara", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Hidemasa", "last_name": "Bono", "name": null }, { "creator_type": "author", "first_name": "Itoshi", "last_name": "Nikaido", "name": null }, { "creator_type": "author", "first_name": "Takeya", "last_name": "Kasukawa", "name": null }, { "creator_type": "author", "first_name": "Yoshihide", "last_name": "Hayashizaki", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Okazaki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1101/gr.974603" }, "pmcid": { "normalized": "PMC403659" }, "pmid": { "normalized": "12819132" } }, "mesh": [ { "descriptor": "Amino Acids", "descriptor_ui": "D000596", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Computational Biology", "descriptor_ui": "D019295", "major_topic": false }, { "descriptor": "Databases, Genetic", "descriptor_ui": "D030541", "major_topic": false }, { "descriptor": "Genome", "descriptor_ui": "D016678", "major_topic": true }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Models, Biological", "descriptor_ui": "D008954", "major_topic": false }, { "descriptor": "Models, Genetic", "descriptor_ui": "D008957", "major_topic": false }, { "descriptor": "Proteins", "descriptor_ui": "D011506", "major_topic": false }, { "descriptor": "Transcription, Genetic", "descriptor_ui": "D014158", "major_topic": false } ], "publication": { "conference_name": null, "date": "2003 Jun", "date_precision": "unknown", "issue": "6B", "normalized_date": null, "pages": "1345-1349", "proceedings_title": null, "publisher": "", "title": "Genome research", "volume": "13", "year": 2003 }, "ssbd": { "database": [], "repository": [] }, "title": "Comprehensive analysis of the mouse metabolome based on the transcriptome.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Candidate imprinted transcriptional units in the mouse genome were identified systematically from 27,663 FANTOM2 full-length mouse cDNA clones by expression profiling. Large-scale cDNA microarrays were used to detect differential expression dependent upon chromosomal parent of origin by comparing the mRNA levels in the total tissue of 9.5 dpc parthenogenote and androgenote mouse embryos. Of the FANTOM2 transcripts, 2114 were identified as candidates on the basis of the array data. Of these, 39 mapped to known imprinted regions of the mouse genome, 56 were considered as nonprotein-coding RNAs, and 159 were natural antisense transcripts. The imprinted expression of two transcripts located in the mouse chromosomal region syntenic to the human Prader-Willi syndrome region was confirmed experimentally. We further mapped all candidate imprinted transcripts to the mouse and human genome and were shown in correlation with the imprinting disease loci. These data provide a major resource for understanding the role of imprinting in mammalian inherited traits.", "classifications": [ { "id": "Nikaido", "label": "Group Nikaido", "parent": "Fujiwara", "type": "group" }, { "id": "Fujiwara", "label": "Team Fujiwara", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Itoshi", "last_name": "Nikaido", "name": null }, { "creator_type": "author", "first_name": "Chika", "last_name": "Saito", "name": null }, { "creator_type": "author", "first_name": "Yosuke", "last_name": "Mizuno", "name": null }, { "creator_type": "author", "first_name": "Makiko", "last_name": "Meguro", "name": null }, { "creator_type": "author", "first_name": "Hidemasa", "last_name": "Bono", "name": null }, { "creator_type": "author", "first_name": "Moritoshi", "last_name": "Kadomura", "name": null }, { "creator_type": "author", "first_name": "Tomohiro", "last_name": "Kono", "name": null }, { "creator_type": "author", "first_name": "Gerard A.", "last_name": "Morris", "name": null }, { "creator_type": "author", "first_name": "Paul A.", "last_name": "Lyons", "name": null }, { "creator_type": "author", "first_name": "Mitsuo", "last_name": "Oshimura", "name": null }, { "creator_type": "author", "first_name": "Yoshihide", "last_name": "Hayashizaki", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Okazaki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1101/gr.1055303" }, "pmcid": { "normalized": "PMC403673" }, "pmid": { "normalized": "12819139" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Chromosome Mapping", "descriptor_ui": "D002874", "major_topic": false }, { "descriptor": "Databases, Genetic", "descriptor_ui": "D030541", "major_topic": false }, { "descriptor": "Embryo, Mammalian", "descriptor_ui": "D004622", "major_topic": false }, { "descriptor": "Gene Expression Profiling", "descriptor_ui": "D020869", "major_topic": false }, { "descriptor": "Genetic Markers", "descriptor_ui": "D005819", "major_topic": false }, { "descriptor": "Genomic Imprinting", "descriptor_ui": "D018392", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Mice, Inbred Strains", "descriptor_ui": "D008815", "major_topic": false }, { "descriptor": "Oligonucleotide Array Sequence Analysis", "descriptor_ui": "D020411", "major_topic": false }, { "descriptor": "Prader-Willi Syndrome", "descriptor_ui": "D011218", "major_topic": false }, { "descriptor": "RNA, Messenger", "descriptor_ui": "D012333", "major_topic": false }, { "descriptor": "RNA, Untranslated", "descriptor_ui": "D022661", "major_topic": false }, { "descriptor": "Sequence Homology, Nucleic Acid", "descriptor_ui": "D012689", "major_topic": false }, { "descriptor": "Transcription, Genetic", "descriptor_ui": "D014158", "major_topic": false } ], "publication": { "conference_name": null, "date": "2003 Jun", "date_precision": "unknown", "issue": "6B", "normalized_date": null, "pages": "1402-1409", "proceedings_title": null, "publisher": "", "title": "Genome research", "volume": "13", "year": 2003 }, "ssbd": { "database": [], "repository": [] }, "title": "Discovery of imprinted transcripts in the mouse transcriptome using large-scale expression profiling.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "We describe a method, based on pressure-assisted capillary electrophoresis coupled to electrospray ionization mass spectrometry (PACE/ESI-MS), that allows the simultaneous and quantitative analysis of multivalent anions, such as citrate isomers, nucleotides, nicotinamide-adenine dinucleotides, and flavin adenine dinucleotide, and coenzyme A (CoA) compounds. Key to the analysis was using a noncharged polymer, poly(dimethylsiloxane), coated to the inner surface of the capillary to prevent anionic species from adsorbing onto the capillary wall. It was also necessary to drive a constant liquid flow toward the MS by applying air pressure to the inlet capillary during electrophoresis to maintain a conductive liquid junction between the capillary and the electrospray needle. Although theoretical plates were inferior to those obtained by CE/ESI-MS using a cationic polymer-coated capillary, the PACE/ESI-MS method improved reproducibility and sensitivity of these anions. Eighteen anions were separated by PACE and selectively detected by a quadrupole mass spectrometer with a sheath-flow electrospray ionization interface. The relative standard deviations (n = 6) of the method were better than 0.6% for migration times and between 1.4% and 6.2% for peak areas. The detection limits for these species were between 0.4 and 3.7 micromol/L with pressure injection of 50 mbar for 30 s (30 nL), that is, mass detection limits calculated in the range from 12 to 110 fmol at a signal-to-noise ratio of 3. The utility of the method was demonstrated by analysis of citrate isomers, nucleotides, dinucleotides, and CoA compounds extracted from Bacillus subtilis cells.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Ueno", "name": null }, { "creator_type": "author", "first_name": "Hisako", "last_name": "Naraoka", "name": null }, { "creator_type": "author", "first_name": "Keiko", "last_name": "Matsuda", "name": null }, { "creator_type": "author", "first_name": "Masaru", "last_name": "Tomita", "name": null }, { "creator_type": "author", "first_name": "Takaaki", "last_name": "Nishioka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/ac0202684" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "12510742" } }, "mesh": [ { "descriptor": "Anions", "descriptor_ui": "D000838", "major_topic": false }, { "descriptor": "Bacillus subtilis", "descriptor_ui": "D001412", "major_topic": false }, { "descriptor": "Citrates", "descriptor_ui": "D002951", "major_topic": false }, { "descriptor": "Coenzyme A", "descriptor_ui": "D003065", "major_topic": false }, { "descriptor": "Electrophoresis, Capillary", "descriptor_ui": "D019075", "major_topic": false }, { "descriptor": "Nucleotides", "descriptor_ui": "D009711", "major_topic": false }, { "descriptor": "Pressure", "descriptor_ui": "D011312", "major_topic": false }, { "descriptor": "Reproducibility of Results", "descriptor_ui": "D015203", "major_topic": false }, { "descriptor": "Sensitivity and Specificity", "descriptor_ui": "D012680", "major_topic": false }, { "descriptor": "Spectrometry, Mass, Electrospray Ionization", "descriptor_ui": "D021241", "major_topic": false } ], "publication": { "conference_name": null, "date": "2002 Dec 15", "date_precision": "day", "issue": "24", "normalized_date": "2002-12-15", "pages": "6224-6229", "proceedings_title": null, "publisher": "", "title": "Analytical chemistry", "volume": "74", "year": 2002 }, "ssbd": { "database": [], "repository": [] }, "title": "Pressure-assisted capillary electrophoresis electrospray ionization mass spectrometry for analysis of multivalent anions.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Transforming growth factor-β (TGF-β), when bound to its specific receptor, activates the transcription factor Smad by phosphorylation. TGF-β also activates the p38 MAPK pathway, but there seem to be disparate mechanisms for the early p38 activation and delayed p38 activation. In this report, we demonstrate that Smad-dependent expression of GADD45β is responsible for the delayed activation of p38 by TGF-β. The GADD45β protein binds and activates MTK1 (= MEKK4), which is a member of the MAPKKK family kinases and an upstream activator of the p38 MAPK cascade. Both TGF-β-induced GADD45β expression and the delayed p38 activation require functional Smad proteins. Antisense inhibition of GADD45β expression suppresses the TGF-β-induced delayed p38 activation, whereas overexpression of GADD45β activates the p38 MAPK via MTK1. Expression of the angiogenesis inhibitor thrombospondin-1 (TSP-1) is induced by TGF-β via Smad-dependent p38 activation. Thus TGF-β-induced p38 activation, mediated by GADD45β expression, may play an important role in the biological effects of TGF-β.", "classifications": [ { "id": "Takekawa", "label": "Group Takekawa", "parent": "Takekawa", "type": "group" }, { "id": "Takekawa", "label": "Team Takekawa", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Mutsuhiro", "last_name": "Takekawa", "name": null }, { "creator_type": "author", "first_name": "Kazuo", "last_name": "Tatebayashi", "name": null }, { "creator_type": "author", "first_name": "Fumio", "last_name": "Itoh", "name": null }, { "creator_type": "author", "first_name": "Masaaki", "last_name": "Adachi", "name": null }, { "creator_type": "author", "first_name": "Kohzoh", "last_name": "Imai", "name": null }, { "creator_type": "author", "first_name": "Haruo", "last_name": "Saito", "name": null } ], "identifiers": { "doi": { "normalized": "10.1093/emboj/cdf643" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "12456654" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Antigens, Differentiation", "descriptor_ui": "D000943", "major_topic": false }, { "descriptor": "Blotting, Northern", "descriptor_ui": "D015152", "major_topic": false }, { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "COS Cells", "descriptor_ui": "D019556", "major_topic": false }, { "descriptor": "DNA-Binding Proteins", "descriptor_ui": "D004268", "major_topic": false }, { "descriptor": "GADD45 Proteins", "descriptor_ui": "D000097642", "major_topic": false }, { "descriptor": "HeLa Cells", "descriptor_ui": "D006367", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Mitogen-Activated Protein Kinases", "descriptor_ui": "D020928", "major_topic": false }, { "descriptor": "p38 Mitogen-Activated Protein Kinases", "descriptor_ui": "D048051", "major_topic": false }, { "descriptor": "Pancreas", "descriptor_ui": "D010179", "major_topic": false }, { "descriptor": "Smad4 Protein", "descriptor_ui": "D051901", "major_topic": false }, { "descriptor": "Thrombospondin 1", "descriptor_ui": "D019700", "major_topic": false }, { "descriptor": "Trans-Activators", "descriptor_ui": "D015534", "major_topic": false }, { "descriptor": "Transforming Growth Factor beta", "descriptor_ui": "D016212", "major_topic": false } ], "publication": { "conference_name": null, "date": "2002 Dec 2", "date_precision": "day", "issue": "23", "normalized_date": "2002-12-02", "pages": "6473-6482", "proceedings_title": null, "publisher": "", "title": "The EMBO Journal", "volume": "21", "year": 2002 }, "ssbd": { "database": [], "repository": [] }, "title": "Smad-dependent GADD45β expression mediates delayed activation of p38 MAP kinase by TGF-β.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "BACKGROUND: Calcium antagonists normalize endothelial dysfunction in many cardiovascular diseases. There is no known receptor, however, for calcium antagonists in endothelial cells (ECs). We hypothesized that vascular smooth muscle cells (VSMCs) are involved in the mechanism underlying the normalization of endothelial dysfunction by calcium antagonists. METHODS AND RESULTS: Coculture studies with ECs and VSMCs were performed to determine whether VSMCs mediate modulation of endothelial superoxide dismutase (SOD) activity and expression induced by the calcium antagonist nifedipine. Nifedipine induced upregulation of SOD activity in rat aortic segments but had no effect on SOD expression or activity in ECs or VSMCs cultured individually. When ECs were cocultured with VSMCs, however, nifedipine upregulated SOD expression and activity in ECs. Nifedipine stimulated vascular endothelial growth factor (VEGF) production from VSMCs, and this stimulation of VEGF production was abolished by HOE-140, an antagonist of the bradykinin B(2) receptor. A neutralizing antibody against VEGF inhibited the upregulation of endothelial SOD by nifedipine. In addition, recombinant VEGF induced an increase in the levels of SOD expression in ECs, and supernatant derived from nifedipine-treated VSMCs enhanced NO production from ECs. This increase in NO production by the supernatant was inhibited by preincubation of ECs with SOD antisense oligodeoxyribonucleotides. CONCLUSIONS: The calcium antagonist nifedipine indirectly upregulates endothelial SOD expression by stimulating VEGF production from adjacent VSMCs. This finding may provide further insight into the mechanism underlying the beneficial effects of calcium antagonists in cardiovascular diseases.", "classifications": [ { "id": "Suzuki", "label": "Group Suzuki", "parent": "Takekawa", "type": "group" }, { "id": "Takekawa", "label": "Team Takekawa", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Keisuke", "last_name": "Fukuo", "name": null }, { "creator_type": "author", "first_name": "Jin", "last_name": "Yang", "name": null }, { "creator_type": "author", "first_name": "Osamu", "last_name": "Yasuda", "name": null }, { "creator_type": "author", "first_name": "Masaki", "last_name": "Mogi", "name": null }, { "creator_type": "author", "first_name": "Toshimitsu", "last_name": "Suhara", "name": null }, { "creator_type": "author", "first_name": "Naoyuki", "last_name": "Sato", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Shigeto", "last_name": "Morimoto", "name": null }, { "creator_type": "author", "first_name": "Toshio", "last_name": "Ogihara", "name": null } ], "identifiers": { "doi": { "normalized": "10.1161/01.cir.0000021924.02006.ba" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "12119253" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Aorta", "descriptor_ui": "D001011", "major_topic": false }, { "descriptor": "Calcium Channel Blockers", "descriptor_ui": "D002121", "major_topic": false }, { "descriptor": "Cell Communication", "descriptor_ui": "D002450", "major_topic": false }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Coculture Techniques", "descriptor_ui": "D018920", "major_topic": false }, { "descriptor": "Endothelial Growth Factors", "descriptor_ui": "D016228", "major_topic": false }, { "descriptor": "Endothelium, Vascular", "descriptor_ui": "D004730", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Lymphokines", "descriptor_ui": "D008222", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Muscle, Smooth, Vascular", "descriptor_ui": "D009131", "major_topic": false }, { "descriptor": "Nifedipine", "descriptor_ui": "D009543", "major_topic": false }, { "descriptor": "Nitric Oxide", "descriptor_ui": "D009569", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Rats, Wistar", "descriptor_ui": "D017208", "major_topic": false }, { "descriptor": "Receptors, Bradykinin", "descriptor_ui": "D018002", "major_topic": false }, { "descriptor": "Superoxide Dismutase", "descriptor_ui": "D013482", "major_topic": false }, { "descriptor": "Up-Regulation", "descriptor_ui": "D015854", "major_topic": false }, { "descriptor": "Vascular Endothelial Growth Factor A", "descriptor_ui": "D042461", "major_topic": false }, { "descriptor": "Vascular Endothelial Growth Factors", "descriptor_ui": "D042442", "major_topic": false } ], "publication": { "conference_name": null, "date": "2002 Jul 16", "date_precision": "day", "issue": "3", "normalized_date": "2002-07-16", "pages": "356-361", "proceedings_title": null, "publisher": "", "title": "Circulation", "volume": "106", "year": 2002 }, "ssbd": { "database": [], "repository": [] }, "title": "Nifedipine indirectly upregulates superoxide dismutase expression in endothelial cells via vascular smooth muscle cell-dependent pathways.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "We have identified a novel epidermal growth factor (EGF)-like repeat-containing single-pass transmembrane protein that is specifically expressed in the developing and mature central nervous system. Sequence analysis revealed that the 10 EGF-like repeats in the extracellular domain are closely related to those of the developmentally important receptor Notch and its ligand Delta. We thus named the molecule Delta/Notch-like EGF-related receptor (DNER). DNER protein is strongly expressed in several types of post-mitotic neurons, including cortical and hippocampal pyramidal neurons, cerebellar granule cells, and Purkinje cells. DNER protein is localized to the dendritic plasma membrane and endosomes and is excluded from the axons, even when overexpressed. The tyrosine-based sorting motif in the cytoplasmic domain is required for dendritic targeting of DNER. Direct in vivo binding of DNER to the coat-associated protein complex AP-1 strongly suggests that DNER undergoes AP-1-dependent sorting to the somatodendritic compartments from the trans-Golgi network and subsequent passage through the endosomal system.", "classifications": [ { "id": "Eiraku", "label": "Group Eiraku", "parent": "Eiraku", "type": "group" }, { "id": "Eiraku", "label": "Team Eiraku", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Mototsugu", "last_name": "Eiraku", "name": null }, { "creator_type": "author", "first_name": "Yutaka", "last_name": "Hirata", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Takeshima", "name": null }, { "creator_type": "author", "first_name": "Tomoo", "last_name": "Hirano", "name": null }, { "creator_type": "author", "first_name": "Mineko", "last_name": "Kengaku", "name": null } ], "identifiers": { "doi": { "normalized": "10.1074/jbc.m110793200" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "11950833" } }, "mesh": [ { "descriptor": "Amino Acid Sequence", "descriptor_ui": "D000595", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Central Nervous System", "descriptor_ui": "D002490", "major_topic": false }, { "descriptor": "Endocytosis", "descriptor_ui": "D004705", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Immunohistochemistry", "descriptor_ui": "D007150", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Molecular Sequence Data", "descriptor_ui": "D008969", "major_topic": false }, { "descriptor": "Nerve Tissue Proteins", "descriptor_ui": "D009419", "major_topic": false }, { "descriptor": "Neurons", "descriptor_ui": "D009474", "major_topic": false }, { "descriptor": "Protein Binding", "descriptor_ui": "D011485", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Receptors, Cell Surface", "descriptor_ui": "D011956", "major_topic": false }, { "descriptor": "RNA, Messenger", "descriptor_ui": "D012333", "major_topic": false }, { "descriptor": "Sequence Homology, Amino Acid", "descriptor_ui": "D017386", "major_topic": false }, { "descriptor": "Transcription Factor AP-1", "descriptor_ui": "D018808", "major_topic": false } ], "publication": { "conference_name": null, "date": "2002 Jul 12", "date_precision": "day", "issue": "28", "normalized_date": "2002-07-12", "pages": "25400-25407", "proceedings_title": null, "publisher": "", "title": "The Journal of biological chemistry", "volume": "277", "year": 2002 }, "ssbd": { "database": [], "repository": [] }, "title": "Delta/notch-like epidermal growth factor (EGF)-related receptor, a novel EGF-like repeat-containing protein targeted to dendrites of developing and adult central nervous system neurons.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Mitogen-activated protein kinases (MAPKs) must be precisely inactivated to achieve proper functions in the cells. Ten members of dual specificity phosphatases specifically acting on MAPKs, termed MAPK phosphatases (MKPs), have been reported. Each member has its own substrate specificity that should be tightly regulated. However, the molecular mechanism underlying the regulation of the specificity is largely unknown. In the MAPK signaling pathways, docking interactions, which are different from transient enzyme-substrate interaction, are known to regulate the enzymatic specificity. Here we have identified and characterized a docking surface of MKPs. Our results show that a docking surface is composed of a tandem alignment of three subregions (modules): a cluster of positively charged amino acids, a cluster of hydrophobic amino acids, and a cluster of positively charged amino acids (positive-hydrophobic-positive). This modular structure well fits the docking groove on MAPKs that we have previously identified and may contribute to regulating the docking specificity of the MKP family. The position, number, and species of charged amino acids in each module including the central hydrophobic subregion are important factors in regulation of docking to specific MAPKs. This modular structure in the docking interaction may define a novel model of protein-protein interaction that would also regulate other systems.", "classifications": [ { "id": "Yamamoto", "label": "Group Yamamoto", "parent": "Toyoshima", "type": "group" }, { "id": "Toyoshima", "label": "Team Toyoshima", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Takuji", "last_name": "Tanoue", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Eisuke", "last_name": "Nishida", "name": null } ], "identifiers": { "doi": { "normalized": "10.1074/jbc.m202096200" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "11953434" } }, "mesh": [ { "descriptor": "Amino Acid Sequence", "descriptor_ui": "D000595", "major_topic": false }, { "descriptor": "Amino Acids", "descriptor_ui": "D000596", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Arginine", "descriptor_ui": "D001120", "major_topic": false }, { "descriptor": "Binding Sites", "descriptor_ui": "D001665", "major_topic": false }, { "descriptor": "Cell Cycle Proteins", "descriptor_ui": "D018797", "major_topic": true }, { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "COS Cells", "descriptor_ui": "D019556", "major_topic": false }, { "descriptor": "Dual Specificity Phosphatase 1", "descriptor_ui": "D054638", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Immediate-Early Proteins", "descriptor_ui": "D017874", "major_topic": false }, { "descriptor": "MAP Kinase Signaling System", "descriptor_ui": "D020935", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mitogen-Activated Protein Kinases", "descriptor_ui": "D020928", "major_topic": false }, { "descriptor": "Models, Biological", "descriptor_ui": "D008954", "major_topic": false }, { "descriptor": "Molecular Sequence Data", "descriptor_ui": "D008969", "major_topic": false }, { "descriptor": "Mutagenesis", "descriptor_ui": "D016296", "major_topic": false }, { "descriptor": "p38 Mitogen-Activated Protein Kinases", "descriptor_ui": "D048051", "major_topic": false }, { "descriptor": "Phosphoprotein Phosphatases", "descriptor_ui": "D010749", "major_topic": true }, { "descriptor": "Plasmids", "descriptor_ui": "D010957", "major_topic": false }, { "descriptor": "Precipitin Tests", "descriptor_ui": "D011233", "major_topic": false }, { "descriptor": "Protein Binding", "descriptor_ui": "D011485", "major_topic": false }, { "descriptor": "Protein Phosphatase 1", "descriptor_ui": "D054645", "major_topic": false }, { "descriptor": "Protein Structure, Tertiary", "descriptor_ui": "D017434", "major_topic": false }, { "descriptor": "Protein Tyrosine Phosphatases", "descriptor_ui": "D017027", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Sequence Homology, Amino Acid", "descriptor_ui": "D017386", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false }, { "descriptor": "Substrate Specificity", "descriptor_ui": "D013379", "major_topic": false } ], "publication": { "conference_name": null, "date": "2002 Jun 21", "date_precision": "day", "issue": "25", "normalized_date": "2002-06-21", "pages": "22942-22949", "proceedings_title": null, "publisher": "", "title": "The Journal of biological chemistry", "volume": "277", "year": 2002 }, "ssbd": { "database": [], "repository": [] }, "title": "Modular structure of a docking surface on MAPK phosphatases.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "A method for simultaneous determination of anionic metabolites based on capillary electrophoresis (CE) coupled to electrospray ionization mass spectrometry is described. To prevent current drop by the system, electroosmotic flow (EOF) reversal by using a cationic polymer-coated capillary was indispensable. A mixture containing 32 standards including carboxylic acids, phosphorylated carboxylic acids, phosphorylated saccharides, nucleotides, and nicotinamide and flavin adenine coenzymes of glycolysis and the tricarboxylic acid cycle pathways were separated by CE and selectively detected by a quadrupole mass spectrometer with a sheath-flow electrospray ionization interface. Key to the analysis was EOF reversal using a cationic polymer-coated capillary and an electrolyte system consisting of 50 mM ammonium acetate, pH 9.0. The relative standard deviations of the method were better than 0.4% for migration times and between 0.9% and 5.4% for peak areas. The concentration detection limits for these metabolites were between 0.3 and 6.7 micromol/L with pressure injection of 50 mbar for 30 s (30 nL); i.e., mass detection limits ranged from 9 to 200 fmol, at a signal-to-noise ratio of 3. This method was applied to the comprehensive analysis of metabolic intermediates extracted from Bacillus subtilis, and 27 anionic metabolites could be directly detected and quantified.", "classifications": [ { "id": "Soga", "label": "Group Soga", "parent": "Kuroda", "type": "group" }, { "id": "Kuroda", "label": "Team Kuroda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Tomoyoshi", "last_name": "Soga", "name": null }, { "creator_type": "author", "first_name": "Yuki", "last_name": "Ueno", "name": null }, { "creator_type": "author", "first_name": "Hisako", "last_name": "Naraoka", "name": null }, { "creator_type": "author", "first_name": "Yoshiaki", "last_name": "Ohashi", "name": null }, { "creator_type": "author", "first_name": "Masaru", "last_name": "Tomita", "name": null }, { "creator_type": "author", "first_name": "Takaaki", "last_name": "Nishioka", "name": null } ], "identifiers": { "doi": { "normalized": "10.1021/ac020064n" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "12038746" } }, "mesh": [ { "descriptor": "Anions", "descriptor_ui": "D000838", "major_topic": false }, { "descriptor": "Bacillus subtilis", "descriptor_ui": "D001412", "major_topic": false }, { "descriptor": "Carboxylic Acids", "descriptor_ui": "D002264", "major_topic": false }, { "descriptor": "Citric Acid Cycle", "descriptor_ui": "D002952", "major_topic": false }, { "descriptor": "Electrophoresis, Capillary", "descriptor_ui": "D019075", "major_topic": false }, { "descriptor": "Glycolysis", "descriptor_ui": "D006019", "major_topic": false }, { "descriptor": "Sensitivity and Specificity", "descriptor_ui": "D012680", "major_topic": false }, { "descriptor": "Spectrometry, Mass, Electrospray Ionization", "descriptor_ui": "D021241", "major_topic": false } ], "publication": { "conference_name": null, "date": "2002 May 15", "date_precision": "day", "issue": "10", "normalized_date": "2002-05-15", "pages": "2233-2239", "proceedings_title": null, "publisher": "", "title": "Analytical chemistry", "volume": "74", "year": 2002 }, "ssbd": { "database": [], "repository": [] }, "title": "Simultaneous determination of anionic intermediates for Bacillus subtilis metabolic pathways by capillary electrophoresis electrospray ionization mass spectrometry.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Capacitative Ca(2+) entry (CCE) activated by release/depletion of Ca(2+) from internal stores represents a major Ca(2+) influx mechanism in lymphocytes and other nonexcitable cells. Despite the importance of CCE in antigen-mediated lymphocyte activation, molecular components constituting this mechanism remain elusive. Here we demonstrate that genetic disruption of transient receptor potential (TRP)1 significantly attenuates both Ca(2+) release-activated Ca(2+) currents and inositol 1,4,5-trisphosphate (IP(3))-mediated Ca(2+) release from endoplasmic reticulum (ER) in DT40 B cells. As a consequence, B cell antigen receptor-mediated Ca(2+) oscillations and NF-AT activation are reduced in TRP1-deficient cells. Thus, our results suggest that CCE channels, whose formation involves TRP1 as an important component, modulate IP(3) receptor function, thereby enhancing functional coupling between the ER and plasma membrane in transduction of intracellular Ca(2+) signaling in B lymphocytes.", "classifications": [ { "id": "Nishida", "label": "Group Nishida", "parent": "Nishida", "type": "group" }, { "id": "Nishida", "label": "Team Nishida", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yasuo", "last_name": "Mori", "name": null }, { "creator_type": "author", "first_name": "Minoru", "last_name": "Wakamori", "name": null }, { "creator_type": "author", "first_name": "Tomoya", "last_name": "Miyakawa", "name": null }, { "creator_type": "author", "first_name": "Meredith", "last_name": "Hermosura", "name": null }, { "creator_type": "author", "first_name": "Yuji", "last_name": "Hara", "name": null }, { "creator_type": "author", "first_name": "Motohiro", "last_name": "Nishida", "name": null }, { "creator_type": "author", "first_name": "Kenzo", "last_name": "Hirose", "name": null }, { "creator_type": "author", "first_name": "Akiko", "last_name": "Mizushima", "name": null }, { "creator_type": "author", "first_name": "Mari", "last_name": "Kurosaki", "name": null }, { "creator_type": "author", "first_name": "Emiko", "last_name": "Mori", "name": null }, { "creator_type": "author", "first_name": "Kumiko", "last_name": "Gotoh", "name": null }, { "creator_type": "author", "first_name": "Takaharu", "last_name": "Okada", "name": null }, { "creator_type": "author", "first_name": "Andrea", "last_name": "Fleig", "name": null }, { "creator_type": "author", "first_name": "Reinhold", "last_name": "Penner", "name": null }, { "creator_type": "author", "first_name": "Masamitsu", "last_name": "Iino", "name": null }, { "creator_type": "author", "first_name": "Tomohiro", "last_name": "Kurosaki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1084/jem.20011758" }, "pmcid": { "normalized": "PMC2193746" }, "pmid": { "normalized": "11901194" } }, "mesh": [ { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "B-Lymphocytes", "descriptor_ui": "D001402", "major_topic": false }, { "descriptor": "Calcium", "descriptor_ui": "D002118", "major_topic": false }, { "descriptor": "Calcium Channels", "descriptor_ui": "D015220", "major_topic": false }, { "descriptor": "Calcium Signaling", "descriptor_ui": "D020013", "major_topic": true }, { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "Chickens", "descriptor_ui": "D002645", "major_topic": false }, { "descriptor": "Endoplasmic Reticulum", "descriptor_ui": "D004721", "major_topic": false }, { "descriptor": "Gene Deletion", "descriptor_ui": "D017353", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "TRPC Cation Channels", "descriptor_ui": "D050052", "major_topic": false } ], "publication": { "conference_name": null, "date": "2002 Mar 18", "date_precision": "day", "issue": "6", "normalized_date": "2002-03-18", "pages": "673-681", "proceedings_title": null, "publisher": "", "title": "The Journal of experimental medicine", "volume": "195", "year": 2002 }, "ssbd": { "database": [], "repository": [] }, "title": "Transient receptor potential 1 regulates capacitative Ca(2+) entry and Ca(2+) release from endoplasmic reticulum in B lymphocytes.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Genes differentially expressed between parthenogenetic and androgenetic embryos are candidates for the identification of imprinted genes, which are expressed specifically from the maternal or paternal allele. To search for genes differentially expressed between parthenogenetic and androgenetic embryos, we used the RIKEN full-length enriched mouse cDNA microarray. The 25 candidates obtained included 8 known imprinted genes (such as IgfII, Snrpn, and Neuronatin) and 3 new ones--Asb4 (ankyrin repeat and SOCS box-containing protein 4), Ata3 (amino acid transport system A3), and Decorin--which were confirmed by using normal diploid embryos from the reciprocal F1 crosses of B6 and JF1 mice. The 25 candidates also included genes that showed no imprinting-associated expression in normal diploid embryos. We describe a feasible high-throughput method of screening for novel imprinted genes by using the RIKEN cDNA microarray.", "classifications": [ { "id": "Nikaido", "label": "Group Nikaido", "parent": "Fujiwara", "type": "group" }, { "id": "Fujiwara", "label": "Team Fujiwara", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yosuke", "last_name": "Mizuno", "name": null }, { "creator_type": "author", "first_name": "Yusuke", "last_name": "Sotomaru", "name": null }, { "creator_type": "author", "first_name": "Yukiko", "last_name": "Katsuzawa", "name": null }, { "creator_type": "author", "first_name": "Tomohiro", "last_name": "Kono", "name": null }, { "creator_type": "author", "first_name": "Makiko", "last_name": "Meguro", "name": null }, { "creator_type": "author", "first_name": "Mitsuo", "last_name": "Oshimura", "name": null }, { "creator_type": "author", "first_name": "Jun", "last_name": "Kawai", "name": null }, { "creator_type": "author", "first_name": "Yasuhiro", "last_name": "Tomaru", "name": null }, { "creator_type": "author", "first_name": "Hidenori", "last_name": "Kiyosawa", "name": null }, { "creator_type": "author", "first_name": "Itoshi", "last_name": "Nikaido", "name": null }, { "creator_type": "author", "first_name": "Hiroshi", "last_name": "Amanuma", "name": null }, { "creator_type": "author", "first_name": "Yoshihide", "last_name": "Hayashizaki", "name": null }, { "creator_type": "author", "first_name": "Yasushi", "last_name": "Okazaki", "name": null } ], "identifiers": { "doi": { "normalized": "10.1006/bbrc.2002.6370" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "11820791" } }, "mesh": [ { "descriptor": "Amino Acid Transport System A", "descriptor_ui": "D026924", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Ankyrin Repeat", "descriptor_ui": "D017089", "major_topic": false }, { "descriptor": "Autoantigens", "descriptor_ui": "D001324", "major_topic": false }, { "descriptor": "Carrier Proteins", "descriptor_ui": "D002352", "major_topic": false }, { "descriptor": "Decorin", "descriptor_ui": "D058575", "major_topic": false }, { "descriptor": "Embryo, Mammalian", "descriptor_ui": "D004622", "major_topic": false }, { "descriptor": "Extracellular Matrix Proteins", "descriptor_ui": "D016326", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Gene Expression Profiling", "descriptor_ui": "D020869", "major_topic": false }, { "descriptor": "Genetic Testing", "descriptor_ui": "D005820", "major_topic": false }, { "descriptor": "Genomic Imprinting", "descriptor_ui": "D018392", "major_topic": true }, { "descriptor": "Insulin-Like Growth Factor II", "descriptor_ui": "D007335", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Membrane Proteins", "descriptor_ui": "D008565", "major_topic": false }, { "descriptor": "Mice", "descriptor_ui": "D051379", "major_topic": false }, { "descriptor": "Mice, Inbred C57BL", "descriptor_ui": "D008810", "major_topic": false }, { "descriptor": "Nerve Tissue Proteins", "descriptor_ui": "D009419", "major_topic": false }, { "descriptor": "Oligonucleotide Array Sequence Analysis", "descriptor_ui": "D020411", "major_topic": false }, { "descriptor": "Proteoglycans", "descriptor_ui": "D011509", "major_topic": false }, { "descriptor": "Ribonucleoproteins, Small Nuclear", "descriptor_ui": "D017411", "major_topic": true }, { "descriptor": "snRNP Core Proteins", "descriptor_ui": "D055517", "major_topic": false } ], "publication": { "conference_name": null, "date": "2002 Feb 8", "date_precision": "day", "issue": "5", "normalized_date": "2002-02-08", "pages": "1499-1505", "proceedings_title": null, "publisher": "", "title": "Biochemical and biophysical research communications", "volume": "290", "year": 2002 }, "ssbd": { "database": [], "repository": [] }, "title": "Asb4, Ata3, and Dcn are novel imprinted genes identified by high-throughput screening using RIKEN cDNA microarray.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Intracellular Ca2+ waves, which develop under Ca2+-overloaded conditions of the injured myocardium, are regarded as an important substrate for triggered arrhythmias. However, little is known about whether Ca2+ waves arise or become proarrhythmic in the injured heart in situ. On the hypothesis that injured myocardium manifests frequent Ca2+ waves and produce an oscillatory [Ca2+]i rise leading to triggered activity, we applied cryo-injury to the epicardial surface of fluo 3-AM-loaded perfused rat hearts and analyzed spatiotemporal [Ca2+]i changes at border zones of the injured myocardium using real-time confocal microscopy. In intact regions Ca2+ waves barely emerged, whereas the border zone myocardium exhibited frequent Ca2+ waves, propagating randomly within the individual cells. Two different types of Ca2+ waves were identified: highly frequent waves (159.6+/-86.5 waves/min/cell, n=266) adjacent to the cryo-ablated regions, and less frequent waves (79.0+/-50.1 waves/min/cell, n=160) slightly farther (>2 cells) away from the ablated regions (vicinities). The former Ca2+ waves emerged asynchronously to Ca2+ transients. Contrariwise, the latter depended on ventricular excitation: they vanished instantaneously on Ca2+ transients, but emerged more frequently and propagated more swiftly after cessation of higher-frequency pacing. Immediately after 3-Hz pacing, some cryo-injured hearts exhibited oscillatory [Ca2+]i rises; an instantaneous and synchronous elevation of [Ca2+]i followed by burst occurrence of Ca2+ waves with a gradual decrease in incidence and propagation velocity in a considerable number of cells. These observations indicate that myocardial injury induces Ca2+ waves in the heart, and that their synchronous occurrence could become a substrate for triggered arrhythmias.", "classifications": [ { "id": "Tanaka", "label": "Group Tanaka", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Hideo", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Masahito", "last_name": "Oyamada", "name": null }, { "creator_type": "author", "first_name": "Eiji", "last_name": "Tsujii", "name": null }, { "creator_type": "author", "first_name": "Takuya", "last_name": "Nakajo", "name": null }, { "creator_type": "author", "first_name": "Tetsuro", "last_name": "Takamatsu", "name": null } ], "identifiers": { "doi": { "normalized": "10.1006/jmcc.2002.2096" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "12431449" } }, "mesh": [ { "descriptor": "Aniline Compounds", "descriptor_ui": "D000814", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Calcium", "descriptor_ui": "D002118", "major_topic": false }, { "descriptor": "Calcium Signaling", "descriptor_ui": "D020013", "major_topic": false }, { "descriptor": "Cold Temperature", "descriptor_ui": "D003080", "major_topic": false }, { "descriptor": "Computer Systems", "descriptor_ui": "D003199", "major_topic": false }, { "descriptor": "Cytosol", "descriptor_ui": "D003600", "major_topic": false }, { "descriptor": "Fluorescent Dyes", "descriptor_ui": "D005456", "major_topic": false }, { "descriptor": "Heart Injuries", "descriptor_ui": "D006335", "major_topic": false }, { "descriptor": "Image Processing, Computer-Assisted", "descriptor_ui": "D007091", "major_topic": false }, { "descriptor": "Ion Transport", "descriptor_ui": "D017136", "major_topic": false }, { "descriptor": "Male", "descriptor_ui": "D008297", "major_topic": false }, { "descriptor": "Microscopy, Confocal", "descriptor_ui": "D018613", "major_topic": false }, { "descriptor": "Myocardium", "descriptor_ui": "D009206", "major_topic": false }, { "descriptor": "Rats", "descriptor_ui": "D051381", "major_topic": false }, { "descriptor": "Rats, Wistar", "descriptor_ui": "D017208", "major_topic": false }, { "descriptor": "Xanthenes", "descriptor_ui": "D014966", "major_topic": false } ], "publication": { "conference_name": null, "date": "2002 Nov", "date_precision": "unknown", "issue": "11", "normalized_date": null, "pages": "1501-1512", "proceedings_title": null, "publisher": "", "title": "Journal of molecular and cellular cardiology", "volume": "34", "year": 2002 }, "ssbd": { "database": [], "repository": [] }, "title": "Excitation-dependent intracellular Ca2+ waves at the border zone of the cryo-injured rat heart revealed by real-time confocal microscopy.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "A new type of cell-cultivation system based on photo-thermal etching has been developed for the on-chip cultivation of living cells using an agarose microchamber array. The method can be used to flexibly change the chamber structure by photo-thermal etching, even during the cultivation of cells, depending upon the progress in cell growth. We used an infrared (1064 nm) focused laser beam as a heat source to melt and remove agar gel at the heated spot on a thin chromium layer. The melting of the agar occurred just near the chromium thin layer, and the size of the photo-thermally etched area depended almost linearly on the power of the irradiated laser beam from 2 microm to 50 microm. Thus by using photo-thermal etching with adequate laser power we could easily fabricate narrow tunnel-shaped channels between the microchambers at the bottom of the agar-layer even during cell cultivation. After 48 h of cultivation of nerve cells, the nerve cells in two adjacent chambers made fiber connections through the fabricated narrow tunnel-shaped channels. These results suggest that photo-thermal etching occurred only in the area where an absorbing material was used, which means that it is possible to photo-thermally etch lines without damaging the cells in the microchambers. The results also suggest that the agar-microchamber cell cultivation system in combination with photo-thermal etching can potentially be used for the next stage of single cell cultivation including the real-time control of the interaction of cells during cell cultivation.", "classifications": [ { "id": "Wakamoto", "label": "Group Wakamoto", "parent": "Wakamoto", "type": "group" }, { "id": "Wakamoto", "label": "Team Wakamoto", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Hiroyuki", "last_name": "Moriguchi", "name": null }, { "creator_type": "author", "first_name": "Yuichi", "last_name": "Wakamoto", "name": null }, { "creator_type": "author", "first_name": "Yoshihiro", "last_name": "Sugio", "name": null }, { "creator_type": "author", "first_name": "Kazunori", "last_name": "Takahashi", "name": null }, { "creator_type": "author", "first_name": "Ippei", "last_name": "Inoue", "name": null }, { "creator_type": "author", "first_name": "Kenji", "last_name": "Yasuda", "name": null } ], "identifiers": { "doi": { "normalized": "10.1039/b202569h" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "15100846" } }, "mesh": [], "publication": { "conference_name": null, "date": "2002 May", "date_precision": "unknown", "issue": "2", "normalized_date": null, "pages": "125-132", "proceedings_title": null, "publisher": "", "title": "Lab on a chip", "volume": "2", "year": 2002 }, "ssbd": { "database": [], "repository": [] }, "title": "An agar-microchamber cell-cultivation system: flexible change of microchamber shapes during cultivation by photo-thermal etching.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "We have previously demonstrated by immunohistochemistry the presence of secreted carbonic anhydrase (CA VI) in the acinar cells of the rat lacrimal glands. In this study we purified the sheep lacrimal gland CA VI to homogeneity and demonstrated by Western analysis that it has the same apparent subunit molecular weight (45 kD) as the enzyme isolated from saliva. RT-PCR analysis showed that CA VI mRNA from the lacrimal gland was identical to that of the parotid gland CA VI mRNA. An RIA specific for sheep CA VI showed the lacrimal gland tissue concentration of the enzyme to be 4.20 +/- 2.60 ng/mg protein, or about 1/7000 of the level found in the parotid gland. Immunohistochemistry (IHC) and in situ hybridization (ISH) showed that lacrimal acinar cells expressed both immunoreactivity and mRNA for CA VI. Moreover, CA VI immunoreactivity was occasionally observed in the lumen of the ducts. Unlike the parotid gland, in which all acinar cells expressed CA VI immunoreactivity and mRNA, only some of the acinar cells of the lacrimal gland showed expression. These results indicate that the lacrimal gland synthesizes and secretes a very small amount of salivary CA VI. In tear fluid, CA VI is presumed to have a role in the maintenance of acid/base balance on the surface of the eye, akin to its role in the oral cavity.", "classifications": [ { "id": "Suzuki", "label": "Group Suzuki", "parent": "Takekawa", "type": "group" }, { "id": "Takekawa", "label": "Team Takekawa", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yuzo", "last_name": "Ogawa", "name": null }, { "creator_type": "author", "first_name": "Keiji", "last_name": "Matsumoto", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Maeda", "name": null }, { "creator_type": "author", "first_name": "Riyoko", "last_name": "Tamai", "name": null }, { "creator_type": "author", "first_name": "Takashi", "last_name": "Suzuki", "name": null }, { "creator_type": "author", "first_name": "Hironobu", "last_name": "Sasano", "name": null }, { "creator_type": "author", "first_name": "Ross T.", "last_name": "Fernley", "name": null } ], "identifiers": { "doi": { "normalized": "10.1177/002215540205000608" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "12019298" } }, "mesh": [ { "descriptor": "Amino Acid Sequence", "descriptor_ui": "D000595", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Base Sequence", "descriptor_ui": "D001483", "major_topic": false }, { "descriptor": "Blotting, Western", "descriptor_ui": "D015153", "major_topic": false }, { "descriptor": "Carbonic Anhydrase IV", "descriptor_ui": "D030741", "major_topic": false }, { "descriptor": "Female", "descriptor_ui": "D005260", "major_topic": false }, { "descriptor": "Immunohistochemistry", "descriptor_ui": "D007150", "major_topic": false }, { "descriptor": "In Situ Hybridization", "descriptor_ui": "D017403", "major_topic": false }, { "descriptor": "Lacrimal Apparatus", "descriptor_ui": "D007765", "major_topic": false }, { "descriptor": "Molecular Sequence Data", "descriptor_ui": "D008969", "major_topic": false }, { "descriptor": "Radioimmunoassay", "descriptor_ui": "D011863", "major_topic": false }, { "descriptor": "Reverse Transcriptase Polymerase Chain Reaction", "descriptor_ui": "D020133", "major_topic": false }, { "descriptor": "Sheep", "descriptor_ui": "D012756", "major_topic": false } ], "publication": { "conference_name": null, "date": "2002 Jun", "date_precision": "unknown", "issue": "6", "normalized_date": null, "pages": "821-827", "proceedings_title": null, "publisher": "", "title": "The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society", "volume": "50", "year": 2002 }, "ssbd": { "database": [], "repository": [] }, "title": "Characterization of lacrimal gland carbonic anhydrase VI.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "A variety of cellular stresses activate the stress-responsive mitogen-activated protein (MAP) kinases p38 and JNK. In this study, we studied the activation mechanism of a human MAP kinase kinase kinase, MTK1 (also known as MEKK4), which mediates activation of both p38 and JNK. MTK1 has an extensive N-terminal noncatalytic domain composed of ∼1,300 amino acids. Full-length or near full-length MTK1 is catalytically inactive when expressed in Saccharomyces cerevisiae cells, as it is in mammalian cells. Deletion of a segment including positions 253 to 553 activates kinase, indicating that this segment contains the autoinhibitory domain. In the autoinhibited conformation, the MTK1 kinase domain cannot interact with its substrate, MKK6. By a functional complementation screening with yeast cells, GADD45 proteins (GADD45α, β, and γ) were identified as MTK1 activators. GADD45 proteins bind a site in MTK1 near the inhibitory domain and relieve autoinhibition. Mutants of full-length MTK1 were isolated that can interact with MKK6 in the absence of the activator GADD45 proteins. These MTK1 mutants are constitutively active, in both yeast and mammalian cells. A model of MTK1 autoinhibition by the N-terminal inhibitory domain and activation by GADD45 binding is presented.", "classifications": [ { "id": "Takekawa", "label": "Group Takekawa", "parent": "Takekawa", "type": "group" }, { "id": "Takekawa", "label": "Team Takekawa", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Hiroaki", "last_name": "Mita", "name": null }, { "creator_type": "author", "first_name": "Junichiro", "last_name": "Tsutsui", "name": null }, { "creator_type": "author", "first_name": "Mutsuhiro", "last_name": "Takekawa", "name": null }, { "creator_type": "author", "first_name": "Elizabeth A.", "last_name": "Witten", "name": null }, { "creator_type": "author", "first_name": "Haruo", "last_name": "Saito", "name": null } ], "identifiers": { "doi": { "normalized": "10.1128/mcb.22.13.4544-4555.2002" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "12052864" } }, "mesh": [ { "descriptor": "Binding Sites", "descriptor_ui": "D001665", "major_topic": false }, { "descriptor": "Calcium-Calmodulin-Dependent Protein Kinases", "descriptor_ui": "D017871", "major_topic": false }, { "descriptor": "Catalytic Domain", "descriptor_ui": "D020134", "major_topic": false }, { "descriptor": "GADD45 Proteins", "descriptor_ui": "D000097642", "major_topic": false }, { "descriptor": "Genetic Complementation Test", "descriptor_ui": "D005816", "major_topic": false }, { "descriptor": "HeLa Cells", "descriptor_ui": "D006367", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "Intracellular Signaling Peptides and Proteins", "descriptor_ui": "D047908", "major_topic": false }, { "descriptor": "MAP Kinase Kinase 6", "descriptor_ui": "D048669", "major_topic": false }, { "descriptor": "MAP Kinase Kinase Kinase 4", "descriptor_ui": "D048768", "major_topic": false }, { "descriptor": "MAP Kinase Kinase Kinases", "descriptor_ui": "D020930", "major_topic": false }, { "descriptor": "Mutation", "descriptor_ui": "D009154", "major_topic": false }, { "descriptor": "Peptide Fragments", "descriptor_ui": "D010446", "major_topic": false }, { "descriptor": "Proteins", "descriptor_ui": "D011506", "major_topic": false }, { "descriptor": "Saccharomyces cerevisiae", "descriptor_ui": "D012441", "major_topic": false } ], "publication": { "conference_name": null, "date": "2002 Jul", "date_precision": "unknown", "issue": "13", "normalized_date": null, "pages": "4544-4555", "proceedings_title": null, "publisher": "", "title": "Molecular and Cellular Biology", "volume": "22", "year": 2002 }, "ssbd": { "database": [], "repository": [] }, "title": "Regulation of MTK1/MEKK4 Kinase Activity by Its N-Terminal Autoinhibitory Domain and GADD45 Binding.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "IL-1β converting enzyme (ICE) family cysteine proteases are subdivided into three groups; ICE-, CPP32-, and Ich-1–like proteases. In Fas-induced apoptosis, activation of ICE-like proteases is followed by activation of CPP32-like proteases which is thought to be essential for execution of the cell death. It was recently reported that two subfamily members of the mitogen-activated protein kinase superfamily, JNK/SAPK and p38, are activated during Fas-induced apoptosis. Here, we have shown that MKK7, but not SEK1/ MKK4, is activated by Fas as an activator for JNK/ SAPK and that MKK6 is a major activator for p38 in Fas signaling. Then, to dissect various cellular responses induced by Fas, we used several peptide inhibitors for ICE family proteases in Fas-treated Jurkat cells and KB cells. While Z-VAD-FK which inhibited almost all the Fas-induced cellular responses blocked the activation of JNK/SAPK and p38, Ac-DEVD-CHO and Z-DEVD-FK, specific inhibitors for CPP32-like proteases, which inhibited the Fas-induced chromatin condensation and DNA fragmentation did not block the activation of JNK/SAPK and p38. Interestingly, these DEVD-type inhibitors did not block the Fas-induced morphological changes (cell shrinkage and surface blebbing), induction of Apo2.7 antigen, or the cell death (as assessed by the dye exclusion ability). These results suggest that the Fas-induced activation of the JNK/SAPK and p38 signaling pathways does not require CPP32-like proteases and that CPP32-like proteases, although essential for apoptotic nuclear events (such as chromatin condensation and DNA fragmentation), are not required for other apoptotic events in the cytoplasm or the cell death itself. Thus, the Fas signaling pathway diverges into multiple, separate processes, each of which may be responsible for part of the apoptotic cellular responses.", "classifications": [ { "id": "Toyoshima", "label": "Group Toyoshima", "parent": "Toyoshima", "type": "group" }, { "id": "Toyoshima", "label": "Team Toyoshima", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Fumiko", "last_name": "Toyoshima", "name": null }, { "creator_type": "author", "first_name": "Tetsuo", "last_name": "Moriguchi", "name": null }, { "creator_type": "author", "first_name": "Eisuke", "last_name": "Nishida", "name": null } ], "identifiers": { "doi": { "normalized": null }, "pmcid": { "normalized": null }, "pmid": { "normalized": "9362518" } }, "mesh": [ { "descriptor": "Apoptosis", "descriptor_ui": "D017209", "major_topic": true }, { "descriptor": "Calcium-Calmodulin-Dependent Protein Kinases", "descriptor_ui": "D017871", "major_topic": false }, { "descriptor": "Caspase 3", "descriptor_ui": "D053148", "major_topic": false }, { "descriptor": "Caspases", "descriptor_ui": "D020169", "major_topic": true }, { "descriptor": "Cell Line", "descriptor_ui": "D002460", "major_topic": false }, { "descriptor": "Cysteine Endopeptidases", "descriptor_ui": "D003546", "major_topic": false }, { "descriptor": "Enzyme Activation", "descriptor_ui": "D004789", "major_topic": false }, { "descriptor": "fas Receptor", "descriptor_ui": "D019014", "major_topic": false }, { "descriptor": "Humans", "descriptor_ui": "D006801", "major_topic": false }, { "descriptor": "JNK Mitogen-Activated Protein Kinases", "descriptor_ui": "D048031", "major_topic": false }, { "descriptor": "MAP Kinase Kinase 6", "descriptor_ui": "D048669", "major_topic": false }, { "descriptor": "MAP Kinase Kinase 7", "descriptor_ui": "D048688", "major_topic": false }, { "descriptor": "Mitogen-Activated Protein Kinase Kinases", "descriptor_ui": "D020929", "major_topic": true }, { "descriptor": "Mitogen-Activated Protein Kinases", "descriptor_ui": "D020928", "major_topic": true }, { "descriptor": "Protease Inhibitors", "descriptor_ui": "D011480", "major_topic": false }, { "descriptor": "Protein Kinases", "descriptor_ui": "D011494", "major_topic": false }, { "descriptor": "Signal Transduction", "descriptor_ui": "D015398", "major_topic": false } ], "publication": { "conference_name": null, "date": "1997 Nov 17", "date_precision": "day", "issue": "4", "normalized_date": "1997-11-17", "pages": "1005-1015", "proceedings_title": null, "publisher": "", "title": "The Journal of Cell Biology", "volume": "139", "year": 1997 }, "ssbd": { "database": [], "repository": [] }, "title": "Fas Induces Cytoplasmic Apoptotic Responses and Activation of the MKK7-JNK/SAPK and MKK6-p38 Pathways Independent of CPP32-like Proteases .", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Mechanisms underlying β-adrenoceptor stimulation by dopamine were examined on guinea-pig Langendorff-perfused hearts and isolated cells from the right atrium, by using the chronotropic effects and the enhancement of L-type Ca2+ current (ICa,L) in the presence of prazosin as indicators of β-adrenoceptor stimulation. Dopamine-induced overflow of noradrenaline (NA) concentrations was measured by high-performance liquid chromatography.Dopamine caused positive chronotropic effects with an EC50 of 2.5 μM and induced NA overflow with a similar EC50 (1.3 μM). The chronotropic effect of dopamine was abolished by bisoprolol (1 μM).The effects of dopamine were maintained during prolonged application, whereas the effects of tyramine faded with time. Dopamine (3 μM) restored the chronotropic effects and the NA release suppressed by pretreatment with tyramine, suggesting a de novo synthesis of NA during the exposure to dopamine.Dopamine (3 μM)-induced NA release was not affected by tetrodotoxin, ω-conotoxin, rauwolscine, ICI118551 or sulpiride, but was inhibited by desipramine, a NA uptake inhibitor (IC50 ∼1 μM). It was also not affected by GBR12909 and bupropion, dopamine uptake inhibitors in the central nervous system.SKF38393, a D1 receptor partial agonist, potently inhibited the 3 μM dopamine-induced release of NA (IC50 ∼0.1 μM). D1 receptors are not involved in the DA-induced release of NA, since SCH23390 (3 μM), a potent D1 antagonist, inhibited the NA release only slightly, and dihydrexidine (1 μM) and chloro-APB (1 μM), full D1 agonists, caused no significant NA release.SKF38393 inhibited tyramine-induced overflow of NA, and potentiated the field stimulation-induced NA release. SKF38393 and desipramine retarded the decay of the stimulation-induced tachycardia in a similar manner. These results indicate that SKF38393 is a potent monoamine transport inhibitor and a useful tool for the functional evaluation of indirectly-acting sympathomimetic agonists in the heart. In the presence of SKF38393 (10 μM), dopamine at 1 μM showed no chronotropic effect.Voltage clamp experiments with isolated atrial cells revealed that dopamine is a weak partial agonist. The EC50 for ICa,L stimulation by dopamine was high (13 μM). As a result, dopamine at 1 μM did not affect ICa,L. Bisoprolol abolished the stimulation of ICa,L by dopamine (30 μM), and dihydrexidine (1 μM) did not affect ICa,L.It was concluded that the cardiac effects of dopamine at clinically relevant concentrations (<1 μM) result almost exclusively from the indirect effect of β adrenoceptor stimulation, involving the release of NA from sympathetic nerve terminals. The roles of the direct stimulation of β adrenoceptors by dopamine at these concentrations and the stimulation of postjunctional D1 receptors seem negligible. The desipramine- and SKF38393-sensitive monoamine transporter mediates the release of NA.", "classifications": [ { "id": "Tanaka", "label": "Group Tanaka", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Yoshizumi", "last_name": "Habuchi", "name": null }, { "creator_type": "author", "first_name": "Hideo", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Manabu", "last_name": "Nishio", "name": null }, { "creator_type": "author", "first_name": "Taku", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Toshiaki", "last_name": "Komori", "name": null }, { "creator_type": "author", "first_name": "Junichiro", "last_name": "Morikawa", "name": null }, { "creator_type": "author", "first_name": "Manabu", "last_name": "Yoshimura", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/sj.bjp.0701574" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "9422813" } }, "mesh": [ { "descriptor": "2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine", "descriptor_ui": "D015647", "major_topic": false }, { "descriptor": "Amines", "descriptor_ui": "D000588", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Dopamine", "descriptor_ui": "D004298", "major_topic": false }, { "descriptor": "Dopamine Agonists", "descriptor_ui": "D018491", "major_topic": false }, { "descriptor": "Guinea Pigs", "descriptor_ui": "D006168", "major_topic": false }, { "descriptor": "Heart", "descriptor_ui": "D006321", "major_topic": false }, { "descriptor": "Membrane Glycoproteins", "descriptor_ui": "D008562", "major_topic": false }, { "descriptor": "Membrane Transport Proteins", "descriptor_ui": "D026901", "major_topic": true }, { "descriptor": "Myocardium", "descriptor_ui": "D009206", "major_topic": false }, { "descriptor": "Neuropeptides", "descriptor_ui": "D009479", "major_topic": true }, { "descriptor": "Neurotransmitter Agents", "descriptor_ui": "D018377", "major_topic": false }, { "descriptor": "Norepinephrine", "descriptor_ui": "D009638", "major_topic": false }, { "descriptor": "Receptors, Adrenergic, beta", "descriptor_ui": "D011943", "major_topic": false }, { "descriptor": "Sympatholytics", "descriptor_ui": "D013565", "major_topic": false }, { "descriptor": "Sympathomimetics", "descriptor_ui": "D013566", "major_topic": false }, { "descriptor": "Vesicular Biogenic Amine Transport Proteins", "descriptor_ui": "D050492", "major_topic": false } ], "publication": { "conference_name": null, "date": "1997 Dec", "date_precision": "unknown", "issue": "8", "normalized_date": null, "pages": "1669-1678", "proceedings_title": null, "publisher": "", "title": "British Journal of Pharmacology", "volume": "122", "year": 1997 }, "ssbd": { "database": [], "repository": [] }, "title": "Dopamine stimulation of cardiac β-adrenoceptors: the involvement of sympathetic amine transporters and the effect of SKF38393.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "The effects of endothelin-1 (ET-1) on sinoatrial (SA) node preparations of the rabbit heart were studied by means of whole-cell clamp techniques.ET-1 at 1 nM slowed the spontaneous beating activity and rendered half of the cells quiescent. At a higher concentration of 10 nM, the slowing and cessation of spontaneous activity were accompanied by hyperpolarization.In voltage-clamp experiments, ET-1 decreased the basal L-type Ca2+ current (ICa(L)) dose-dependently with a half-maximal inhibitory concentration (EC50) of 0.42 nM and maximal inhibitory response (Emax) of 49.5%. The delayed rectifying K+ current (IK) was also reduced by 33.2±11.1% at 1 nM. In addition, an inwardly rectifying K+ current was activated by ET-1 at higher concentrations (EC50=4.8 nM). These ET-1-induced changes in membrane currents were abolished by BQ485 (0.3 μM), a highly selective ETA receptor antagonist.When ICa(L) was inhibited by ET-1 (1 nM), subsequent application of 10 μM ACh showed no additional decrease in ICa(L), suggesting the involvement of cyclic AMP in the effects of ET-1 on ICa(L). In contrast, 1 nM ET-1 further decreased ICa(L) in the presence of 10 μM ACh, suggesting that ET-1 activates some additional mechanism(s) which inhibit ICa(L). The ET-1-induced ICa(L) inhibition was abolished by protein kinase A inhibitory peptide (PKI, 20 μM) or H-89 (5 μM). However, the ICa(L) inhibition was not affected by methylene blue (10 μM), suggesting a minor role for cyclic GMP in the effect of ET-1 under basal conditions.ET-1 failed to inhibit ICa(L) when the pipette contained GDPβS (200 μM). However, incubation of the cells with pertussis toxin (PTX, 5 μg ml−1, >6 h) only reduced the ET-1-induced inhibition to 21.5±9.5%, whereas it abolished the inhibitory effect of ACh on ICa(L).Intracellular perfusion of 8-bromo cyclicAMP (8-Br cyclicAMP, 500 μM) attenuated, but did not abolish the inhibitory effect of ET-1 on ICa(L). This 8-Br cyclicAMP-resistant component (17.5±14.4%, n=20) was not affected by combined application of 8-Br cyclicAMP with 8-bromo cyclicGMP (500 μM), ryanodine (1 μM) or phorbol-12-myristate-13-acetate (TPA; 50 nM).In summary, ET-1 exerts negative chronotropic effects on the SA node via ETA-receptors. ET-1 inhibits both ICa(L) and IK, and increases background K+ current. The inhibition of ICa(L) by ET-1 is mainly due to reduction of the cyclicAMP levels via PTX-sensitive G protein, but some other mechanism(s) also seems to be operative.", "classifications": [ { "id": "Tanaka", "label": "Group Tanaka", "parent": "Fujita", "type": "group" }, { "id": "Fujita", "label": "Team Fujita", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Hideo", "last_name": "Tanaka", "name": null }, { "creator_type": "author", "first_name": "Yoshizumi", "last_name": "Habuchi", "name": null }, { "creator_type": "author", "first_name": "Taku", "last_name": "Yamamoto", "name": null }, { "creator_type": "author", "first_name": "Manabu", "last_name": "Nishio", "name": null }, { "creator_type": "author", "first_name": "Junichiro", "last_name": "Morikawa", "name": null }, { "creator_type": "author", "first_name": "Manabu", "last_name": "Yoshimura", "name": null } ], "identifiers": { "doi": { "normalized": "10.1038/sj.bjp.0701370" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "9313942" } }, "mesh": [ { "descriptor": "Acetylcholine", "descriptor_ui": "D000109", "major_topic": false }, { "descriptor": "Animals", "descriptor_ui": "D000818", "major_topic": false }, { "descriptor": "Calcium Channels", "descriptor_ui": "D015220", "major_topic": false }, { "descriptor": "Cells, Cultured", "descriptor_ui": "D002478", "major_topic": false }, { "descriptor": "Depression, Chemical", "descriptor_ui": "D003864", "major_topic": false }, { "descriptor": "Endothelin-1", "descriptor_ui": "D019332", "major_topic": false }, { "descriptor": "Heart Rate", "descriptor_ui": "D006339", "major_topic": false }, { "descriptor": "Patch-Clamp Techniques", "descriptor_ui": "D018408", "major_topic": false }, { "descriptor": "Potassium Channels", "descriptor_ui": "D015221", "major_topic": false }, { "descriptor": "Rabbits", "descriptor_ui": "D011817", "major_topic": false }, { "descriptor": "Sinoatrial Node", "descriptor_ui": "D012849", "major_topic": false } ], "publication": { "conference_name": null, "date": "1997 Sep", "date_precision": "unknown", "issue": "2", "normalized_date": null, "pages": "321-329", "proceedings_title": null, "publisher": "", "title": "British Journal of Pharmacology", "volume": "122", "year": 1997 }, "ssbd": { "database": [], "repository": [] }, "title": "Negative chronotropic actions of endothelin-1 on rabbit sinoatrial node pacemaker cells.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "", "classifications": [ { "id": "JPMJCR2121", "label": "JPMJCR2121", "researcher": "Minako Ueda", "type": "grant" }, { "id": "Tsugawa", "label": "Group Tsugawa", "parent": "Ueda", "type": "group" }, { "id": "Ueda", "label": "Group Ueda", "parent": "Ueda", "type": "group" }, { "id": "Ueda", "label": "Team Ueda", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Zichen", "last_name": "Kang", "name": null }, { "creator_type": "author", "first_name": "Tomonobu", "last_name": "Nonoyama", "name": null }, { "creator_type": "author", "first_name": "Yukitaka", "last_name": "Ishimoto", "name": null }, { "creator_type": "author", "first_name": "Hikari", "last_name": "Matsumoto", "name": null }, { "creator_type": "author", "first_name": "Sakumi", "last_name": "Nakagawa", "name": null }, { "creator_type": "author", "first_name": "Minako", "last_name": "Ueda", "name": null }, { "creator_type": "author", "first_name": "Satoru", "last_name": "Tsugawa", "name": null } ], "identifiers": { "doi": { "normalized": "10.1017/qpb.2024.13" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "39777034" } }, "mesh": [], "publication": { "conference_name": null, "date": "", "date_precision": "unknown", "issue": "", "normalized_date": null, "pages": "", "proceedings_title": null, "publisher": "", "title": "Quantitative Plant Biology", "volume": "5", "year": null }, "ssbd": { "database": [], "repository": [] }, "title": "A viscoelastic–plastic deformation model of hemisphere-like tip growth in Arabidopsis zygotes.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "Innate and goal-directed movements require a high-degree of trunk and appendicular muscle coordination to preserve body stability while ensuring the correct execution of the motor action. The spinal neural circuits underlying motor execution and postural stability are finely modulated by propriospinal, sensory and descending feedback, yet how distinct spinal neuron populations cooperate to control body stability and limb coordination remains unclear. Here, we identified a spinal microcircuit composed of V2 lineage-derived excitatory (V2a) and inhibitory (V2b) neurons that together coordinate ipsilateral body movements during locomotion. Inactivation of the entire V2 neuron lineage does not impair intralimb coordination but destabilizes body balance and ipsilateral limb coupling, causing mice to adopt a compensatory festinating gait and be unable to execute skilled locomotor tasks. Taken together our data suggest that during locomotion the excitatory V2a and inhibitory V2b neurons act antagonistically to control intralimb coordination, and synergistically to coordinate forelimb and hindlimb movements. Thus, we suggest a new circuit architecture, by which neurons with distinct neurotransmitter identities employ a dual-mode of operation, exerting either synergistic or opposing functions to control different facets of the same motor behavior.", "classifications": [ { "id": "Imayoshi", "label": "Group Imayoshi", "parent": "Imayoshi", "type": "group" }, { "id": "Imayoshi", "label": "Team Imayoshi", "type": "team" } ], "creators": [ { "creator_type": "author", "first_name": "Marito", "last_name": "Hayashi", "name": null }, { "creator_type": "author", "first_name": "Miriam", "last_name": "Gullo", "name": null }, { "creator_type": "author", "first_name": "Gokhan", "last_name": "Senturk", "name": null }, { "creator_type": "author", "first_name": "Stefania", "last_name": "Di Costanzo", "name": null }, { "creator_type": "author", "first_name": "Shinji C.", "last_name": "Nagasaki", "name": null }, { "creator_type": "author", "first_name": "Ryoichiro", "last_name": "Kageyama", "name": null }, { "creator_type": "author", "first_name": "Itaru", "last_name": "Imayoshi", "name": null }, { "creator_type": "author", "first_name": "Martyn", "last_name": "Goulding", "name": null }, { "creator_type": "author", "first_name": "Samuel L.", "last_name": "Pfaff", "name": null }, { "creator_type": "author", "first_name": "Graziana", "last_name": "Gatto", "name": null } ], "identifiers": { "doi": { "normalized": "10.1101/2023.03.21.533603" }, "pmcid": { "normalized": null }, "pmid": { "normalized": "36993220" } }, "mesh": [], "publication": { "conference_name": null, "date": "", "date_precision": "unknown", "issue": "", "normalized_date": null, "pages": "", "proceedings_title": null, "publisher": "", "title": "bioRxiv", "volume": "", "year": null }, "ssbd": { "database": [], "repository": [] }, "title": "A spinal synergy of excitatory and inhibitory neurons coordinates ipsilateral body movements.", "url": "", "zotero": { "item_type": "journalArticle" } }, { "abstract": "For successful chimeric antigen receptor T (CAR-T) cell therapy, CAR-T cells must be manufactured without failure caused by suboptimal expansion. In order to determine risk factors for CAR-T cell manufacturing failure, we performed a nationwide cohort study in Japan and analysed patients with diffuse large B-cell lymphoma (DLBCL) who underwent tisagenlecleucel production. We compared clinical factors between 30 cases that failed (7.4%) with those that succeeded (n = 378). Among the failures, the proportion of patients previously treated with bendamustine (43.3% vs. 14.8%; p < 0.001) was significantly higher, and their platelet counts (12.0 vs. 17.0 × 104/μL; p = 0.01) and CD4/CD8 T-cell ratio (0.30 vs. 0.56; p < 0.01) in peripheral blood at apheresis were significantly lower than in the successful group. Multivariate analysis revealed that repeated bendamustine use with short washout periods prior to apheresis (odds ratio [OR], 5.52; p = 0.013 for ≥6 cycles with washout period of 3–24 months; OR, 57.09; p = 0.005 for ≥3 cycles with washout period of <3 months), low platelet counts (OR, 0.495 per 105/μL; p = 0.022) or low CD4/CD8 ratios (